pmid title sentence year journal region virus mutation mutation_start mutation_end gene gene_start gene_end disease disease_start disease_end 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. 1999 Journal of virology Title HIV P236L 4 9 10421243 Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. 1999 Journal of acquired immune deficiency syndromes (1999) Title HIV M184V 64 69 RT;PR 42;139 63;147 10428942 A new point mutation (P157S) in the reverse transcriptase of human immunodeficiency virus type 1 confers low-level resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine. A new point mutation (P157S) in the reverse transcriptase of human immunodeficiency virus type 1 confers low-level resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine. 1999 Antimicrobial agents and chemotherapy Title HIV P157S 22 27 RT 36 57 10441120 Backbone dynamics of the N-terminal domain of the HIV-1 capsid protein and comparison with the G94D mutant conferring cyclosporin resistance/dependence. Backbone dynamics of the N-terminal domain of the HIV-1 capsid protein and comparison with the G94D mutant conferring cyclosporin resistance/dependence. 1999 Biochemistry Title HIV G94D 95 99 Capsid 56 62 10482597 Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. 1999 Journal of virology Title HIV L74V;L74V;M184V 129;177;210 137;185;219 RT;RT;RT 62;85;165 83;87;167 10505677 Rapid detection of the HIV type 1 reverse transcriptase codon T215Y by reverse transcription-polymerase chain reaction with fluorogenic probes. Rapid detection of the HIV type 1 reverse transcriptase codon T215Y by reverse transcription-polymerase chain reaction with fluorogenic probes. 1999 AIDS research and human retroviruses Title HIV T215Y 62 67 RT;RT;Pol 71;34;93 92;55;103 10617626 Site-specific incorporation of nucleoside analogs by HIV-1 reverse transcriptase and the template grip mutant P157S. Template interactions influence substrate recognition at the polymerase active site. Site-specific incorporation of nucleoside analogs by HIV-1 reverse transcriptase and the template grip mutant P157S. 2000 The Journal of biological chemistry Title HIV P157S 110 115 RT 59 80 10682159 Different outcome in the first two patients with an HIV-1 multinucleoside drug-resistant T69SSS insertion in Spain. Different outcome in the first two patients with an HIV-1 multinucleoside drug-resistant T69SSS insertion in Spain. 1999 Antiviral therapy Title HIV T69SSS 89 95 10715167 Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. 2000 Journal of medicinal chemistry Title HIV P236L 136 141 RT 47 68 10729133 The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. 2000 Journal of virology Title HIV M184V 4 9 RT 26 47 10756056 A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. 2000 Journal of virology Title HIV N88S 60 64 PR 50 58 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. 2000 The Journal of biological chemistry Title HIV K65R;L74V 65;74 69;78 RT 169 190 10877852 Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor 8-Cl TIBO: contribution of the L100I and Y181C variants to protein stability and biological activity. Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor 8-Cl TIBO: contribution of the L100I and Y181C variants to protein stability and biological activity. 2000 Protein engineering Title HIV L100I;Y181C 131;141 136;146 RT 34 55 10983633 Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission. Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission. 2000 AIDS (London, England) Title HIV K103N 22 27 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. 2000 Journal of virology Title HIV Q151L 27 32 11000239 Comparison of second-strand transfer requirements and RNase H cleavages catalyzed by human immunodeficiency virus type 1 reverse transcriptase (RT) and E478Q RT. Comparison of second-strand transfer requirements and RNase H cleavages catalyzed by human immunodeficiency virus type 1 reverse transcriptase (RT) and E478Q RT. 2000 Journal of virology Title HIV E478Q 152 157 RT;RT;RT 121;144;158 142;146;160 11009599 Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. 2000 Biochemistry Title HIV I84V;V82F 98;93 102;97 PR 43 51 11060499 Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. Incidence, association with other mutations, and effects on the structure of mutated reverse transcriptase. Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. 2000 Journal of biomedical science Title HIV L210W 9 14 RT 24 45 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. 2000 Journal of virology Title HIV T69G 198 224 11181387 Prevalence and conditions of selection of E44D/A and V118I human immunodeficiency virus type 1 reverse transcriptase mutations in clinical practice. Prevalence and conditions of selection of E44D/A and V118I human immunodeficiency virus type 1 reverse transcriptase mutations in clinical practice. 2001 Antimicrobial agents and chemotherapy Title HIV E44A;E44D;V118I 42;42;53 48;48;58 RT 95 116 11258890 Structural and functional analysis of the HIV gp41 core containing an Ile573 to Thr substitution: implications for membrane fusion. Structural and functional analysis of the HIV gp41 core containing an Ile573 to Thr substitution: implications for membrane fusion. 2001 Biochemistry Title HIV I573T 70 83 gp41 46 50 11264389 Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. 2001 Journal of virology Title HIV T69G 36 65 RT 105 126 11300789 The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. 2001 Biochemistry Title HIV Y181C 4 9 NNRTI;RT 61;26 96;47 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. 2001 Journal of molecular biology Title HIV K103N 4 13 RT 32 34 11389511 Prevalence of the T215Y mutation in human immunodeficiency virus type 1-infected pregnant women in a New York cohort, 1995--1999. Prevalence of the T215Y mutation in human immunodeficiency virus type 1-infected pregnant women in a New York cohort, 1995--1999. 2001 Clinical infectious diseases Title HIV T215Y 18 23 11418520 Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors. Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors. 2001 The Journal of antimicrobial chemotherapy Title HIV K103N;Y181C 16;29 21;34 NNRTI 81 117 11491416 Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. 2001 Antiviral therapy Title HIV M184V 80 85 RT 39 60 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. 2001 Virology Title HIV W229Y 168 177 RT;Pol;RT;RT 90;143;113;185 111;153;115;187 11506064 HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. 2001 Microbios Title HIV Q151M 51 56 11597403 Antiviral drug design: computational analyses of the effects of the L100I mutation for HIV-RT on the binding of NNRTIs. Antiviral drug design: computational analyses of the effects of the L100I mutation for HIV-RT on the binding of NNRTIs. 2001 Bioorganic & medicinal chemistry letters Title HIV L100I 68 73 NNRTI;RT 112;91 118;93 11679914 Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. 2001 The Journal of infectious diseases Title HIV E89G;M184V 53;43 57;48 RT 11 32 11773409 A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site. A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site. 2002 Journal of virology Title HIV A28S 112 116 PR;PR 45;134 53;142 11793380 Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. 2002 Journal of medical virology Title HIV E44A;E44D;V118I 37;37;51 43;43;56 RT;RT;RT 64;87;155 85;89;157 11805439 Prevalence and genetic heterogeneity of the reverse transcriptase T69S-S-X insertion in pretreated HIV-infected patients. Prevalence and genetic heterogeneity of the reverse transcriptase T69S-S-X insertion in pretreated HIV-infected patients. 2001 Intervirology Title HIV T69S 66 70 RT 44 65 HIV infections 99 111 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. 2002 Antimicrobial agents and chemotherapy Title HIV D30N;L90M 21;30 25;34 PR 67 75 11865396 T69D/N pol mutation, human immunodeficiency virus type 1 RNA levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy. T69D/N pol mutation, human immunodeficiency virus type 1 RNA levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy. 2002 The Journal of infectious diseases Title HIV T69D;T69N 0;0 6;6 Pol 7 10 11884549 The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. 2002 Journal of virology Title HIV M184V 4 9 RT 96 117 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. 2002 European journal of biochemistry Title HIV K103N 111 116 RT 108 110 11927582 Mechanistic role of residue Gln151 in error prone DNA synthesis by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. 2002 The Journal of biological chemistry Title HIV Q151N 38 43 RT 50 52 12010361 The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. 2002 HIV medicine Title HIV M184V 18 23 RT 46 67 12021341 Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. 2002 Journal of virology Title HIV M184V 72 77 RT 90 111 12050397 A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. 2002 Journal of virology Title HIV Y318F 94 99 NNRTI;RT 117;71 152;92 12060879 Discordant Human Immunodeficiency Virus Type 1 drug resistance mutations, including K103N, observed in cerebrospinal fluid and plasma. Discordant Human Immunodeficiency Virus Type 1 drug resistance mutations, including K103N, observed in cerebrospinal fluid and plasma. 2002 Clinical infectious diseases Title HIV K103N 84 89 12069983 Pressure of zidovudine accelerates the reversion of lamivudine resistance-conferring M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1. Pressure of zidovudine accelerates the reversion of lamivudine resistance-conferring M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1. 2002 Antimicrobial agents and chemotherapy Title HIV M184V 85 90 RT 107 128 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. 2002 Journal of virology Title HIV I50V 92 96 PR;Gag 97;47 105;50 12163585 Nelfinavir-resistant, amprenavir-hypersusceptible strains of human immunodeficiency virus type 1 carrying an N88S mutation in protease have reduced infectivity, reduced replication capacity, and reduced fitness and process the Gag polyprotein precursor aberrantly. Nelfinavir-resistant, amprenavir-hypersusceptible strains of human immunodeficiency virus type 1 carrying an N88S mutation in protease have reduced infectivity, reduced replication capacity, and reduced fitness and process the Gag polyprotein precursor aberrantly. 2002 Journal of virology Title HIV N88S 109 113 PR;Gag 126;227 134;230 12163615 The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus. The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus. 2002 Journal of virology Title HIV M184V 4 9 RT 22 43 12172093 M184V is associated with a low incidence of thymidine analogue mutations and low phenotypic resistance to zidovudine and stavudine. M184V is associated with a low incidence of thymidine analogue mutations and low phenotypic resistance to zidovudine and stavudine. 2002 AIDS (London, England) Title HIV M184V 0 5 12194983 The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using alpha-boranophosphate nucleotide analogues. The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using alpha-boranophosphate nucleotide analogues. 2002 The Journal of biological chemistry Title HIV Q151M 55 60 RT 97 118 12368302 Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. 2002 Journal of virology Title HIV R166A;V165A 103;93 108;98 IN 125 134 12370512 The prevalence and determinants of the K65R mutation in HIV-1 reverse transcriptase in tenofovir-naive patients. The prevalence and determinants of the K65R mutation in HIV-1 reverse transcriptase in tenofovir-naive patients. 2002 AIDS (London, England) Title HIV K65R 39 43 RT 62 83 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. 2002 Antimicrobial agents and chemotherapy Title HIV K65R;K65R;M184V 111;120;125 115;124;130 RT 79 100 12406504 Interactions of enantiomers of 2',3'-didehydro-2',3'-dideoxy-fluorocytidine with wild type and M184V mutant HIV-1 reverse transcriptase. Interactions of enantiomers of 2',3'-didehydro-2',3'-dideoxy-fluorocytidine with wild type and M184V mutant HIV-1 reverse transcriptase. 2002 Antiviral research Title HIV M184V 95 100 RT 114 135 12435689 Mutagenically separated PCR assay for rapid detection of M41L and K70R zidovudine resistance mutations in CRF01_AE (subtype E) human immunodeficiency virus type 1. Mutagenically separated PCR assay for rapid detection of M41L and K70R zidovudine resistance mutations in CRF01_AE (subtype E) human immunodeficiency virus type 1. 2002 Antimicrobial agents and chemotherapy Title HIV K70R;M41L 66;57 70;61 12461412 The M184V mutation in HIV-1 reverse transcriptase reduces the restoration of wild-type replication by attenuated viruses. The M184V mutation in HIV-1 reverse transcriptase reduces the restoration of wild-type replication by attenuated viruses. 2002 AIDS (London, England) Title HIV M184V 4 9 RT 28 49 12478089 A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors. A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors. 2003 AIDS (London, England) Title HIV V106M 2 7 NNRTI 91 127 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. 2003 Journal of virology Title HIV M184V 17 22 RT 65 86 12543687 Lamivudine can exert a modest antiviral effect against human immunodeficiency virus type 1 containing the M184V mutation. Lamivudine can exert a modest antiviral effect against human immunodeficiency virus type 1 containing the M184V mutation. 2003 Antimicrobial agents and chemotherapy Title HIV M184V 106 111 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? Might the M184V substitution in HIV-1 RT confer clinical benefit? 2002 AIDS reviews Title HIV M184V 10 15 RT 38 40 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? Might the M184V substitution in HIV-1 RT confer clinical benefit? The M184V substitution in HIV-1 RT develops rapidly following initiation of therapy with 3TC and confers high-level phenotypic resistance to this drug both in vitro and in vivo. 2002 AIDS reviews Title HIV M184V 10 15 RT;RT 38;98 40;100 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? Might the M184V substitution in HIV-1 RT confer clinical benefit. 2002 AIDS reviews Title HIV M184V 10 15 12620807 Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. 2003 Virology Title HIV G140S 59 101 IN;IN 36;147 45;156 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. 2003 Antiviral therapy Title HIV M184V 120 125 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. 2003 Journal of virology Title HIV K65R 103 107 12741624 Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. 2003 Antiviral therapy Title HIV M184V 84 89 NRTI 117 121 HIV infections 33 47 12741630 K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. 2003 Antiviral therapy Title HIV K65R 0 4 12750404 Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. 2003 The Journal of clinical investigation Title HIV R77Q 4 8 Vpr 0 3 HIV infections 53 66 12781181 The role of 2',3'-unsaturation on the antiviral activity of anti-HIV nucleosides against 3TC-resistant mutant (M184V). The role of 2',3'-unsaturation on the antiviral activity of anti-HIV nucleosides against 3TC-resistant mutant (M184V). 2003 Bioorganic & medicinal chemistry letters Title HIV M184V 111 116 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. 2003 The Journal of biological chemistry Title HIV E44D;V118I 10;19 14;24 RT 32 53 12821504 The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase delays the development of resistance to amprenavir and efavirenz in subtype B and C clinical isolates. The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase delays the development of resistance to amprenavir and efavirenz in subtype B and C clinical isolates. 2003 Antimicrobial agents and chemotherapy Title HIV M184V 4 9 RT 62 83 12824799 Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudine. Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudine. 2003 AIDS (London, England) Title HIV Y181C;Y181I 30;30 37;37 RT 47 68 12832217 Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. 2003 Virology Title HIV M184V 23 28 RT 47 68 12853755 Low frequency of the V106M mutation among HIV-1 subtype C-infected pregnant women exposed to nevirapine. Low frequency of the V106M mutation among HIV-1 subtype C-infected pregnant women exposed to nevirapine. 2003 AIDS (London, England) Title HIV V106M 21 26 12885880 Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. 2003 Journal of virology Title HIV L74V;M184V 48;57 52;62 RT 80 101 12892062 Natural polymorphisms of protease in protease inhibitor-naive HIV-1 infected patients in Korea: a novel L63M in subtype B. Natural polymorphisms of protease in protease inhibitor-naive HIV-1 infected patients in Korea: a novel L63M in subtype B. 2003 AIDS research and human retroviruses Title HIV L63M 104 108 PR;PR 25;37 33;45 HIV infections 62 76 12898440 Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. 2003 The Journal of infectious diseases Title HIV M184V 23 28 NRTI 104 136 12902345 The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. 2003 The Journal of biological chemistry Title HIV Y181C 4 9 RT 101 122 12920196 Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S). Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S). 2003 Molecular pharmacology Title HIV C280S;F185K 118;112 123;117 IN 36 45 12951121 Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase. Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase. 2003 Bioorganic & medicinal chemistry letters Title HIV K103N 54 59 RT 74 95 12960821 Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. 2003 AIDS (London, England) Title HIV Q151M 34 39 NRTI 84 116 14551187 Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. 2004 The Journal of biological chemistry Title HIV K65R;M184V 105;114 109;119 RT 67 88 14624368 Emergence of minor populations of human immunodeficiency virus type 1 carrying the M184V and L90M mutations in subjects undergoing structured treatment interruptions. Emergence of minor populations of human immunodeficiency virus type 1 carrying the M184V and L90M mutations in subjects undergoing structured treatment interruptions. 2003 The Journal of infectious diseases Title HIV L90M;M184V 93;83 97;88 14690411 Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. 2003 Biochemistry Title HIV A71V;D30N;M36I 29;153;20 33;157;24 PR 77 85 14727218 Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. 2004 Clinical infectious diseases Title HIV Q151M 0 5 14761194 Computer-aided design, synthesis, and anti-HIV-1 activity in vitro of 2-alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-o nes as novel potent non-nucleoside reverse transcriptase inhibitors, also active against the Y181C variant. Computer-aided design, synthesis, and anti-HIV-1 activity in vitro of 2-alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones as novel potent non-nucleoside reverse transcriptase inhibitors, also active against the Y181C variant. 2004 Journal of medicinal chemistry Title HIV Y181C 244 249 NNRTI 171 207 14766874 Different viral rebound following discontinuation of antiretroviral therapy in cases of infection with viruses carrying L74V or thymidine-associated mutations. Different viral rebound following discontinuation of antiretroviral therapy in cases of infection with viruses carrying L74V or thymidine-associated mutations. 2004 Journal of clinical microbiology Title HIV L74V 120 124 15000558 The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection. The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection. 2004 Scandinavian journal of infectious diseases Title HIV V118I 40 45 RT;RT 4;27 25;29 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. 2004 The Journal of biological chemistry Title HIV K65R;L74V 159;168 163;172 RT 125 146 15044738 HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: possible contributions to drug resistance and a potential new target site for drugs. HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: possible contributions to drug resistance and a potential new target site for drugs. 2004 Protein science Title HIV I84V;V82F 65;60 69;64 PR 6 14 15047690 Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA primers. Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA primers. 2004 The Journal of biological chemistry Title HIV D67N;T215Y 174;183 178;188 RT 72 94 15051383 Replication-dependent 65R-->K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V. Replication-dependent 65R-->K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V. 2004 Virology Title HIV K65R;L74V;R65K 115;122;22 119;126;29 RT 79 100 15063744 HIV-1 auxiliary regulatory protein Vpr promotes ubiquitination and turnover of Vpr mutants containing the L64P mutation. HIV-1 auxiliary regulatory protein Vpr promotes ubiquitination and turnover of Vpr mutants containing the L64P mutation. 2004 FEBS letters Title HIV L64P 106 110 Vpr;Vpr 35;79 38;82 15066177 Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site. Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site. 2004 European journal of biochemistry Title HIV L90M;V82A 44;35 48;39 PR 26 34 15072756 HIV protease mutations associated with amprenavir resistance during salvage therapy: importance of I54M. HIV protease mutations associated with amprenavir resistance during salvage therapy: importance of I54M. 2004 Journal of clinical virology Title HIV I54M 99 103 PR 4 12 15084137 Structural and energetic analyses of the effects of the K103N mutation of HIV-1 reverse transcriptase on efavirenz analogues. Structural and energetic analyses of the effects of the K103N mutation of HIV-1 reverse transcriptase on efavirenz analogues. 2004 Journal of medicinal chemistry Title HIV K103N 56 61 RT 80 101 15105107 Effects of drug resistance mutations L100I and V106A on the binding of pyrrolobenzoxazepinone nonnucleoside inhibitors to the human immunodeficiency virus type 1 reverse transcriptase catalytic complex. Effects of drug resistance mutations L100I and V106A on the binding of pyrrolobenzoxazepinone nonnucleoside inhibitors to the human immunodeficiency virus type 1 reverse transcriptase catalytic complex. 2004 Antimicrobial agents and chemotherapy Title HIV L100I;V106A 37;47 42;52 RT 162 183 15122516 Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. 2004 The Journal of infectious diseases Title HIV I50L 18 22 HIV infections 96 110 15155216 Mutation D30N is not preferentially selected by human immunodeficiency virus type 1 subtype C in the development of resistance to nelfinavir. Mutation D30N is not preferentially selected by human immunodeficiency virus type 1 subtype C in the development of resistance to nelfinavir. 2004 Antimicrobial agents and chemotherapy Title HIV D30N 9 13 15196815 Molecular mechanism of dioxolane nucleosides against 3TC resistant M184V mutant HIV. Molecular mechanism of dioxolane nucleosides against 3TC resistant M184V mutant HIV. 2004 Antiviral research Title HIV M184V 67 72 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. 2004 Journal of virology Title HIV D67N;K219E;K219Q 61;69;69 65;76;76 15242545 V118I substitution in the reverse transcriptase gene of HIV type 1 CRF02_AG strains infecting drug-naive individuals in Cameroon. V118I substitution in the reverse transcriptase gene of HIV type 1 CRF02_AG strains infecting drug-naive individuals in Cameroon. 2004 AIDS research and human retroviruses Title HIV V118I 0 5 RT 26 47 15266257 K65R-associated virologic failure in HIV-infected patients receiving tenofovir-containing triple nucleoside/nucleotide reverse transcriptase inhibitor regimens. K65R-associated virologic failure in HIV-infected patients receiving tenofovir-containing triple nucleoside/nucleotide reverse transcriptase inhibitor regimens. 2004 MedGenMed Title HIV K65R 0 4 RT 119 140 HIV infections 37 49 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. 2004 AIDS (London, England) Title HIV M184I;M184V 47;47 54;54 NRTI;RT 122;25 154;46 15332266 High frequency of selection of K65R and Q151M mutations in HIV-2 infected patients receiving nucleoside reverse transcriptase inhibitors containing regimen. High frequency of selection of K65R and Q151M mutations in HIV-2 infected patients receiving nucleoside reverse transcriptase inhibitors containing regimen. 2004 Journal of medical virology Title HIV K65R;Q151M 31;40 35;45 NRTI 93 125 15356825 K103N mutation in antiretroviral therapy-naive African patients infected with HIV type 1. K103N mutation in antiretroviral therapy-naive African patients infected with HIV type 1. 2004 Clinical infectious diseases Title HIV K103N 0 5 15451428 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease dimer complexed with acetyl pepstatin. 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease dimer complexed with acetyl pepstatin. 2004 Biochemical and biophysical research communications Title HIV C1095F;C95M 29;24 35;28 PR 68 76 15452247 Diversity of human immunodeficiency virus type 1 subtype A and CRF03_AB protease in Eastern Europe: selection of the V77I variant and its rapid spread in injecting drug user populations. Diversity of human immunodeficiency virus type 1 subtype A and CRF03_AB protease in Eastern Europe: selection of the V77I variant and its rapid spread in injecting drug user populations. 2004 Journal of virology Title HIV V77I 117 121 PR 72 80 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. 2004 Journal of clinical virology Title HIV G190A 15 20 RT 41 62 15482179 The impact of the M184V substitution on drug resistance and viral fitness. The impact of the M184V substitution on drug resistance and viral fitness. 2004 Expert review of anti-infective therapy Title HIV M184V 18 23 15504840 Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. 2004 Antimicrobial agents and chemotherapy Title HIV M184V 32 37 RT 58 79 15507631 Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. 2004 Journal of virology Title HIV V82A 111 115 PR 149 157 15542562 Insights into saquinavir resistance in the G48V HIV-1 protease: quantum calculations and molecular dynamic simulations. Insights into saquinavir resistance in the G48V HIV-1 protease: quantum calculations and molecular dynamic simulations. 2005 Biophysical journal Title HIV G48V 43 47 PR 54 62 15553926 HIV-1 reverse transcriptase variants: molecular modeling of Y181C, V106A, L100I, and K103N mutations with nonnucleoside inhibitors using Monte Carlo simulations in combination with a linear response method. HIV-1 reverse transcriptase variants: molecular modeling of Y181C, V106A, L100I, and K103N mutations with nonnucleoside inhibitors using Monte Carlo simulations in combination with a linear response method. 2003 Drug design and discovery Title HIV K103N;L100I;V106A;Y181C 85;74;67;60 90;79;72;65 RT 6 27 15561833 Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replication. Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replication. 2004 Antimicrobial agents and chemotherapy Title HIV Q145L;Q145M 0;0 13;13 RT 61 82 15561868 Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. 2004 Antimicrobial agents and chemotherapy Title HIV L23I 94 98 PR;PR 59;105 67;113 15563158 Understanding the basis of resistance in the irksome Lys103Asn HIV-1 reverse transcriptase mutant through targeted molecular dynamics simulations. Understanding the basis of resistance in the irksome Lys103Asn HIV-1 reverse transcriptase mutant through targeted molecular dynamics simulations. 2004 Journal of the American Chemical Society Title HIV K103N 53 62 RT 69 90 15569685 Structural and dynamics studies of the D54A mutant of human T cell leukemia virus-1 capsid protein. Structural and dynamics studies of the D54A mutant of human T cell leukemia virus-1 capsid protein. 2005 The Journal of biological chemistry Title HIV D54A 39 43 Capsid 84 90 15577635 Predictors of selection of K65R: tenofovir use and lack of thymidine analogue mutations. Predictors of selection of K65R: tenofovir use and lack of thymidine analogue mutations. 2004 AIDS (London, England) Title HIV K65R 27 31 15608522 Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. 2005 Journal of acquired immune deficiency syndromes (1999) Title HIV K103N 58 63 15728915 In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase. In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase. 2005 Antimicrobial agents and chemotherapy Title HIV K65R 114 118 RT 131 152 15750116 Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. 2005 Journal of clinical microbiology Title HIV K65R 101 105 15764656 Comparison of multiple molecular dynamics trajectories calculated for the drug-resistant HIV-1 integrase T66I/M154I catalytic domain. Comparison of multiple molecular dynamics trajectories calculated for the drug-resistant HIV-1 integrase T66I/M154I catalytic domain. 2005 Biophysical journal Title HIV M154I;T66I 110;105 115;109 IN 95 104 15802984 Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. 2005 AIDS (London, England) Title HIV K65R;L74V 80;142 84;146 15815973 Comparative molecular dynamics simulations of HIV-1 integrase and the T66I/M154I mutant: binding modes and drug resistance to a diketo acid inhibitor. Comparative molecular dynamics simulations of HIV-1 integrase and the T66I/M154I mutant: binding modes and drug resistance to a diketo acid inhibitor. 2005 Proteins Title HIV M154I;T66I 75;70 80;74 IN 52 61 15840522 Opposing effects of the M368A point mutation and deletion of the SP1 region on membrane binding of human immunodeficiency virus type 1 Gag. Opposing effects of the M368A point mutation and deletion of the SP1 region on membrane binding of human immunodeficiency virus type 1 Gag. 2005 Virology Title HIV M368A 24 29 SP1;Gag 65;135 68;138 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. 2005 Antiviral therapy Title HIV M184V 21 26 RT 45 66 15871131 Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. 2005 The Journal of infectious diseases Title HIV L89M;L90M 114;20 118;24 PR;PR 28;77 36;85 15885814 Effects of HIV Q151M-associated multi-drug resistance mutations on the activities of (-)-beta-D-1',3'-dioxolan guanine. Effects of HIV Q151M-associated multi-drug resistance mutations on the activities of (-)-beta-D-1',3'-dioxolan guanine. 2005 Antiviral research Title HIV Q151M 15 20 15898808 The molecular basis of resilience to the effect of the Lys103Asn mutation in non-nucleoside HIV-1 reverse transcriptase inhibitors studied by targeted molecular dynamics simulations. The molecular basis of resilience to the effect of the Lys103Asn mutation in non-nucleoside HIV-1 reverse transcriptase inhibitors studied by targeted molecular dynamics simulations. 2005 Journal of the American Chemical Society Title HIV K103N 55 64 RT 98 119 15937277 Structural analysis of an HIV-1 protease I47A mutant resistant to the protease inhibitor lopinavir. Structural analysis of an HIV-1 protease I47A mutant resistant to the protease inhibitor lopinavir. 2005 Protein science Title HIV I47A 41 45 PR;PR 32;70 40;78 15942890 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. 2005 The Journal of infectious diseases Title HIV K103N 89 94 15980332 The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. 2005 Antimicrobial agents and chemotherapy Title HIV L74V 4 8 RT 57 78 15980333 Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. 2005 Antimicrobial agents and chemotherapy Title HIV L74V 70 74 RT 123 144 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). 2005 Journal of virology Title HIV K65R;M184I;M184V 29;38;38 33;45;45 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. 2005 Biochemical and biophysical research communications Title HIV L565M 0 5 gp41 24 39 16123676 Effect of the Q207D mutation in HIV type 1 reverse transcriptase on zidovudine susceptibility and replicative fitness. Effect of the Q207D mutation in HIV type 1 reverse transcriptase on zidovudine susceptibility and replicative fitness. 2005 Journal of acquired immune deficiency syndromes (1999) Title HIV Q207D 14 19 RT 43 64 16123677 Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET 012. Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. 2005 Journal of acquired immune deficiency syndromes (1999) Title HIV K103N;Y181C 45;55 50;60 16127058 Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones. Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones. 2005 Antimicrobial agents and chemotherapy Title HIV I50L 21 25 PR 117 125 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. 2005 Antimicrobial agents and chemotherapy Title HIV I50L 108 112 PR 122 130 16183096 The R362A mutation at the C-terminus of CA inhibits packaging of human immunodeficiency virus type 1 RNA. The R362A mutation at the C-terminus of CA inhibits packaging of human immunodeficiency virus type 1 RNA. 2005 Virology Title HIV R362A 4 9 Capsid 40 42 16200350 Structural analysis of reverse transcriptase mutations at codon 215 explains the predominance of T215Y over T215F in HIV-1 variants selected under antiretroviral therapy. Structural analysis of reverse transcriptase mutations at codon 215 explains the predominance of T215Y over T215F in HIV-1 variants selected under antiretroviral therapy. 2005 Journal of biomedical science Title HIV T215F;T215Y 108;97 113;102 RT 23 44 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. 2006 Virology Title HIV K103R 104 109 RT;RT;RT 65;88;144 86;90;146 16226779 The T12I mutation within the SP1 region of Gag restricts packaging of spliced viral RNA into human immunodeficiency virus type 1 with mutated RNA packaging signals and mutated nucleocapsid sequence. The T12I mutation within the SP1 region of Gag restricts packaging of spliced viral RNA into human immunodeficiency virus type 1 with mutated RNA packaging signals and mutated nucleocapsid sequence. 2006 Virology Title HIV T12I 4 8 SP1;Gag 29;43 32;46 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. 2005 AIDS (London, England) Title HIV M89I;M89V 18;18 24;24 PR 0 8 16227803 K65R and Y181C are less prevalent in HAART-experienced HIV-1 subtype A patients. K65R and Y181C are less prevalent in HAART-experienced HIV-1 subtype A patients. 2005 AIDS (London, England) Title HIV Y181C;K65R 9;0 14;4 16245320 Binding energy analysis for wild-type and Y181C mutant HIV-1 RT/8-Cl TIBO complex structures: quantum chemical calculations based on the ONIOM method. Binding energy analysis for wild-type and Y181C mutant HIV-1 RT/8-Cl TIBO complex structures: quantum chemical calculations based on the ONIOM method. 2005 Proteins Title HIV Y181C 42 47 RT 61 63 16260913 Risk of selecting K65R in antiretroviral-naive HIV-infected individuals with chronic hepatitis B treated with adefovir. Risk of selecting K65R in antiretroviral-naive HIV-infected individuals with chronic hepatitis B treated with adefovir. 2005 AIDS (London, England) Title HIV K65R 18 22 Chronic hepatitis B;HIV infections 77;47 96;59 16275650 Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. 2006 The Journal of biological chemistry Title HIV H219P;H219Q 97;87 102;92 Gag 14 17 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. 2005 Journal of molecular biology Title HIV G73S;I50V;L24I 145;135;129 149;139;133 PR 90 98 16312183 Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. 2005 Antiviral therapy Title HIV Q151M 109 114 NRTI;RT 38;131 70;152 16377709 The K101P and K103R/V179D mutations in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nonnucleoside reverse transcriptase inhibitors. The K101P and K103R/V179D mutations in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nonnucleoside reverse transcriptase inhibitors. 2006 Antimicrobial agents and chemotherapy Title HIV K101P;K103R;V179D 4;14;20 9;19;25 NNRTI;RT 118;75 153;96 16386016 In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients. In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients. 2005 The new microbiologica Title HIV K103N 24 29 NNRTI 67 103 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. 2006 Nucleosides, nucleotides & nucleic acids Title HIV K65R;Q151M 59;69 63;74 16470121 Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. 2006 AIDS (London, England) Title HIV R77Q 35 39 Vpr 0 3 HIV infections 89 104 16480273 Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. 2006 Journal of medicinal chemistry Title HIV D30N;I50V;L90M 110;116;126 114;120;130 PR 64 72 16492163 Drug resistance of HIV-1 protease against JE-2147: I47V mutation investigated by molecular dynamics simulation. Drug resistance of HIV-1 protease against JE-2147: I47V mutation investigated by molecular dynamics simulation. 2006 Chemical biology & drug design Title HIV I47V 51 55 PR 25 33 16503141 Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant. Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant. 2006 Bioorganic & medicinal chemistry letters Title HIV K103N 101 106 RT 71 92 16504235 The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. 2006 Virology Title HIV G190A;G190S 50;40 55;45 NNRTI;RT 84;10 120;31 16511398 Transmission of human immunodeficiency virus type 1 nevirapine resistance mutation K103N from a treatment-naive mother to her child. Transmission of human immunodeficiency virus type 1 nevirapine resistance mutation K103N from a treatment-naive mother to her child. 2006 The Pediatric infectious disease journal Title HIV K103N 83 88 16549966 Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. 2006 AIDS (London, England) Title HIV R77A;R77Q;R80A 16;10;25 20;14;29 Vpr 41 44 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. 2006 Journal of medical virology Title HIV K65R 46 50 HIV infections 54 66 16569415 Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. 2006 Journal of molecular biology Title HIV F53L 101 105 PR 87 95 16603851 Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. 2006 AIDS (London, England) Title HIV K103N 9 14 16603864 Prevalence of the HIV-1 protease mutation I47A in clinical practice and association with lopinavir resistance. Prevalence of the HIV-1 protease mutation I47A in clinical practice and association with lopinavir resistance. 2006 AIDS (London, England) Title HIV I47A 42 46 PR 24 32 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. 2006 Antiviral therapy Title HIV K65R 4 8 RT 9 30 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. 2006 Journal of virology Title HIV K65R 4 8 RT 57 78 16644557 Design of nevirapine derivatives insensitive to the K103N and Y181C HIV-1 reverse transcriptase mutants. Design of nevirapine derivatives insensitive to the K103N and Y181C HIV-1 reverse transcriptase mutants. 2006 SAR and QSAR in environmental research Title HIV K103N;Y181C 52;62 57;67 RT 74 95 16771502 Computational simulations of HIV-1 proteases--multi-drug resistance due to nonactive site mutation L90M. Computational simulations of HIV-1 proteases--multi-drug resistance due to nonactive site mutation L90M. 2006 Journal of the American Chemical Society Title HIV L90M 99 103 PR 35 44 16773030 Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. 2006 Journal of acquired immune deficiency syndromes (1999) Title HIV K103N 49 54 16781756 The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. 2006 Virology Title HIV G490E 4 9 RT 22 43 16784458 Optimization and computational evaluation of a series of potential active site inhibitors of the V82F/I84V drug-resistant mutant of HIV-1 protease: an application of the relaxed complex method of structure-based drug design. Optimization and computational evaluation of a series of potential active site inhibitors of the V82F/I84V drug-resistant mutant of HIV-1 protease: an application of the relaxed complex method of structure-based drug design. 2006 Chemical biology & drug design Title HIV I84V;V82F 102;97 106;101 PR 138 146 16794810 Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations. Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations. 2007 Journal of molecular modeling Title HIV E35D 39 43 PR 50 58 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. 2006 Virology Title HIV K103N;L100I;L74V 177;185;229 182;190;233 16801444 Risk factors for selection of the L74I reverse transcriptase mutation in human immunodeficiency virus type 1-infected patients. Risk factors for selection of the L74I reverse transcriptase mutation in human immunodeficiency virus type 1-infected patients. 2006 Antimicrobial agents and chemotherapy Title HIV L74I 34 38 RT 39 60 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. 2006 AIDS (London, England) Title HIV K65R 40 44 16897578 Towards discovering dual functional inhibitors against both wild type and K103N mutant HIV-1 reverse transcriptases: molecular docking and QSAR studies on 4,1-benzoxazepinone analogues. Towards discovering dual functional inhibitors against both wild type and K103N mutant HIV-1 reverse transcriptases: molecular docking and QSAR studies on 4,1-benzoxazepinone analogues. 2006 Journal of computer-aided molecular design Title HIV K103N 74 79 RT 93 115 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. 2006 The Journal of infectious diseases Title HIV K65R 60 64 RT 29 50 16931138 Coexistence of the K65R/L74V and/or K65R/T215Y mutations on the same HIV-1 genome. Coexistence of the K65R/L74V and/or K65R/T215Y mutations on the same HIV-1 genome. 2006 Journal of clinical virology Title HIV K65R;K65R;L74V;T215Y 19;36;24;41 23;40;28;46 16931582 Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. 2006 The Journal of molecular diagnostics Title HIV K103N 72 77 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. 2006 HIV medicine Title HIV K65R 102 106 RT;RT;RT 6;29;107 27;31;109 16970402 HIV-1 protease mutations and inhibitor modifications monitored on a series of complexes. Structural basis for the effect of the A71V mutation on the active site. Structural basis for the effect of the A71V mutation on the active site. 2006 Journal of medicinal chemistry Title HIV A71V 39 43 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. 2006 AIDS research and therapy Title HIV K103N 97 102 RT 41 62 16989618 A rapid and sensitive real-time PCR assay for the K65R drug resistance mutation in SIV reverse transcriptase. A rapid and sensitive real-time PCR assay for the K65R drug resistance mutation in SIV reverse transcriptase. 2006 AIDS research and human retroviruses Title HIV K65R 50 54 RT 87 108 17005757 MultiCode-RTx real-time PCR system for detection of subpopulations of K65R human immunodeficiency virus type 1 reverse transcriptase mutant viruses in clinical samples. MultiCode-RTx real-time PCR system for detection of subpopulations of K65R human immunodeficiency virus type 1 reverse transcriptase mutant viruses in clinical samples. 2006 Journal of clinical microbiology Title HIV K65R 70 74 RT 111 132 17015626 High prevalence of the K65R mutation in human immunodeficiency virus type 1 subtype C isolates from infected patients in Botswana treated with didanosine-based regimens. High prevalence of the K65R mutation in human immunodeficiency virus type 1 subtype C isolates from infected patients in Botswana treated with didanosine-based regimens. 2006 Antimicrobial agents and chemotherapy Title HIV K65R 23 27 17056061 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097. Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097. 2007 Journal of molecular biology Title HIV K103C;K103N;K103Y;Y181C 42;42;42;52 51;51;51;61 RT 82 103 17072129 Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. 2006 The Pediatric infectious disease journal Title HIV M184V 84 89 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. 2007 Antimicrobial agents and chemotherapy Title HIV K70E 33 37 NRTI;RT 130;86 162;107 17096474 The M184V mutation: what it does, how to prevent it, and what to do with it when it's there. The M184V mutation: what it does, how to prevent it, and what to do with it when it's there. 2006 The AIDS reader Title HIV M184V 4 9 17101675 Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication. Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication. 2007 Antimicrobial agents and chemotherapy Title HIV I84A;I84C 59;50 63;54 PR 153 161 17209774 N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. 2006 AIDS research and human retroviruses Title HIV D30N;L90M;N88D 38;47;0 42;51;4 PR 110 118 17243183 Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. 2007 Proteins Title HIV I84V;V82A 76;67 80;71 PR 46 54 17262714 Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission. Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission. 2007 The Journal of infectious diseases Title HIV K103N 15 20 17302373 HIV-1 transmission cluster with M41L 'singleton' mutation and decreased transmission of resistance in newly diagnosed Swedish homosexual men. HIV-1 transmission cluster with M41L 'singleton' mutation and decreased transmission of resistance in newly diagnosed Swedish homosexual men. 2006 Antiviral therapy Title HIV M41L 32 36 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. 2007 The Journal of antimicrobial chemotherapy Title HIV H208Y 17 22 RT;RT;RT 39;62;106 60;64;108 17367119 Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. 2007 Journal of medicinal chemistry Title HIV N88S 36 40 PR 59 67 17413687 Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. 2007 AIDS (London, England) Title HIV K65R;M184V 68;77 72;82 RT 31 52 17413698 Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT. Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT. 2007 AIDS (London, England) Title HIV K65R 89 93 RT 116 118 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. 2007 Retrovirology Title HIV K65R;K70E 78;69 82;73 RT;RT 95;188 116;190 17418430 Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy. Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy. 2007 Antiviral research Title HIV Q151M 73 78 17441703 Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases. Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases. 2007 Journal of medicinal chemistry Title HIV K101E;L100I;Y188C 161;150;176 170;159;185 RT 199 221 17442410 Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase. Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase. 2007 Antiviral research Title HIV K65R;K70E 47;38 51;42 RT 92 113 17503658 The V118I mutation as a marker of advanced HIV infection and disease progression. The V118I mutation as a marker of advanced HIV infection and disease progression. 2007 Antiviral therapy Title HIV V118I 4 9 HIV infections 34 56 17524421 Computational characterization of structural role of the non-active site mutation M36I of human immunodeficiency virus type 1 protease. Computational characterization of structural role of the non-active site mutation M36I of human immunodeficiency virus type 1 protease. 2007 Journal of molecular biology Title HIV M36I 82 86 PR 126 134 17532359 Substitution of alanine for tyrosine-64 in the fingers subdomain of M-MuLV reverse transcriptase impairs strand displacement synthesis and blocks viral replication in vivo. Substitution of alanine for tyrosine-64 in the fingers subdomain of M-MuLV reverse transcriptase impairs strand displacement synthesis and blocks viral replication in vivo. 2007 Virology Title HIV Y64A 16 39 RT 75 96 17543558 Insight into analysis of interactions of saquinavir with HIV-1 protease in comparison between the wild-type and G48V and G48V/L90M mutants based on QM and QM/MM calculations. Insight into analysis of interactions of saquinavir with HIV-1 protease in comparison between the wild-type and G48V and G48V/L90M mutants based on QM and QM/MM calculations. 2007 Journal of molecular graphics & modelling Title HIV G48V;G48V;G48V;G48V;L90M;L90M 112;121;112;121;126;126 116;125;116;125;130;130 PR 63 71 17567542 Mutations at 65 and 70 within the context of a Q151M cluster in human immunodeficiency virus type 1 reverse transcriptase impact the susceptibility to the different nucleoside reverse transcriptase inhibitors in distinct ways. Mutations at 65 and 70 within the context of a Q151M cluster in human immunodeficiency virus type 1 reverse transcriptase impact the susceptibility to the different nucleoside reverse transcriptase inhibitors in distinct ways. 2007 Infection, genetics and evolution Title HIV Q151M 47 52 NRTI;RT 165;100 197;121 17583503 Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. 2007 Bioorganic & medicinal chemistry letters Title HIV K103N;Y181C 114;120 119;125 RT 140 162 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. 2007 AIDS (London, England) Title HIV K65R 57 61 RT 102 123 1761538 Kinetic studies of human immunodeficiency virus type 1 protease and its active-site hydrogen bond mutant A28S. Kinetic studies of human immunodeficiency virus type 1 protease and its active-site hydrogen bond mutant A28S. 1991 The Journal of biological chemistry Title HIV A28S 105 109 PR 55 63 17650515 Detection and quantification of minority HIV isolates harbouring the D30N mutation by real-time PCR amplification. Detection and quantification of minority HIV isolates harbouring the D30N mutation by real-time PCR amplification. 2007 The Journal of antimicrobial chemotherapy Title HIV D30N 69 73 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. 2007 Journal of acquired immune deficiency syndromes (1999) Title HIV K65R 10 14 RT 33 54 17786489 Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant. Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant. 2007 Journal of molecular modeling Title HIV G51D;M46I 119;114 123;118 PR;PR 36;97 44;105 17876005 Novel drug resistance pattern associated with the mutations K70G and M184V in human immunodeficiency virus type 1 reverse transcriptase. Novel drug resistance pattern associated with the mutations K70G and M184V in human immunodeficiency virus type 1 reverse transcriptase. 2007 Antimicrobial agents and chemotherapy Title HIV K70G;M184V 60;69 64;74 RT 114 135 17885291 The presence of the Trim5alpha escape mutation H87Q in the capsid of late stage HIV-1 variants is preceded by a prolonged asymptomatic infection phase. The presence of the Trim5alpha escape mutation H87Q in the capsid of late stage HIV-1 variants is preceded by a prolonged asymptomatic infection phase. 2007 AIDS (London, England) Title HIV H87Q 47 51 Capsid 59 65 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. 2007 AIDS (London, England) Title HIV K103N 13 18 17944683 Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. 2007 HIV medicine Title HIV M184I;M184V 12;12 19;19 17955437 Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients. Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients. 2007 The Journal of infectious diseases Title HIV F214L 51 56 RT 16 37 17967907 Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine. Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine. 2008 Antimicrobial agents and chemotherapy Title HIV G333D 24 29 RT 78 99 17981909 A quantum mechanic/molecular mechanic study of the wild-type and N155S mutant HIV-1 integrase complexed with diketo acid. A quantum mechanic/molecular mechanic study of the wild-type and N155S mutant HIV-1 integrase complexed with diketo acid. 2008 Biophysical journal Title HIV N155S 65 70 IN 84 93 18052235 Caught in the Act: the 1.5 A resolution crystal structures of the HIV-1 protease and the I54V mutant reveal a tetrahedral reaction intermediate. Caught in the Act: the 1.5 A resolution crystal structures of the HIV-1 protease and the I54V mutant reveal a tetrahedral reaction intermediate. 2007 Biochemistry Title HIV I54V 89 93 PR 72 80 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. 2007 PLoS medicine Title HIV N348I 0 5 RT 40 61 18097236 Prevalence and impact of HIV-1 protease mutation L76V on lopinavir resistance. Prevalence and impact of HIV-1 protease mutation L76V on lopinavir resistance. 2008 AIDS (London, England) Title HIV L76V 49 53 PR 31 39 18155520 3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations. 3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations. 2008 Bioorganic & medicinal chemistry letters Title HIV K103N 38 43 RT 57 78 18160002 An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V. An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V. 2007 AIDS research and human retroviruses Title HIV M184I;M184V 168;168 175;175 18195570 Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. 2008 AIDS (London, England) Title HIV V118I 19 24 RT 37 58 18215016 Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation. Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation. 2008 Journal of medicinal chemistry Title HIV V82A 135 139 PR 86 94 18216099 Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. 2008 Journal of virology Title HIV N348I 20 25 NNRTI;RT 163;93 198;114 18218633 Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. 2008 The Journal of biological chemistry Title HIV M184I 47 52 RT 59 80 18240858 Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation. Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation. 2007 Antiviral therapy Title HIV K65R 99 103 RT 77 98 HIV infections 43 55 18252693 The HIV-1 protease substitution K55R: a protease-inhibitor-associated substitution involved in restoring viral replication. The HIV-1 protease substitution K55R: a protease-inhibitor-associated substitution involved in restoring viral replication. 2008 The Journal of antimicrobial chemotherapy Title HIV K55R 32 36 PR;PR 10;40 18;48 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. 2008 Retrovirology Title HIV E40F;K43E 38;62 42;66 RT 90 111 18277921 Vertical transmission of multidrug-resistant Q151M human immunodeficiency virus type 1 strains. Vertical transmission of multidrug-resistant Q151M human immunodeficiency virus type 1 strains. 2008 The Pediatric infectious disease journal Title HIV Q151M 45 50 18281688 Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. 2008 The Journal of biological chemistry Title HIV D25N 26 30 PR 108 116 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. 2008 Journal of clinical virology Title HIV K65R 43 47 HIV infections 64 78 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. 2007 Antiviral chemistry & chemotherapy Title HIV K65R;M184V;M184V 99;105;120 103;110;125 NRTI;RT 20;88 24;90 18327981 Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient. Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient. 2008 AIDS research and human retroviruses Title HIV Y181C 42 47 NNRTI;NNRTI 16;67 21;72 HIV infections 54 66 18338369 A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1 reverse transcriptase based on the ONIOM method. A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1 reverse transcriptase based on the ONIOM method. 2008 ChemMedChem Title HIV K103N;Y181C 62;68 67;73 RT 80 101 18356151 Impact of HIV-1 protease mutations A71V/T and T74S on M89I/V-mediated protease inhibitor resistance in subtype G isolates. Impact of HIV-1 protease mutations A71V/T and T74S on M89I/V-mediated protease inhibitor resistance in subtype G isolates. 2008 The Journal of antimicrobial chemotherapy Title HIV A71T;A71V;M89I;M89V;T74S 35;35;54;54;46 41;41;60;60;50 PR;PR 16;70 24;78 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. 2008 Journal of medical virology Title HIV K70E 93 97 RT 71 92 18370589 Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. 2008 AIDS research and human retroviruses Title HIV K103N 76 81 18419429 Entecavir therapy induces de novo HIV reverse-transcriptase M184V mutation in an antiretroviral therapy-naive patient. Entecavir therapy induces de novo HIV reverse-transcriptase M184V mutation in an antiretroviral therapy-naive patient. 2008 Clinical infectious diseases Title HIV M184V 60 65 RT 38 59 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. 2008 Clinical infectious diseases Title HIV K65R 41 45 HIV infections 63 78 18462084 Drug-resistance mutations number and K70R or T215Y/F substitutions predict treatment resumption during guided treatment interruptions. Drug-resistance mutations number and K70R or T215Y/F substitutions predict treatment resumption during guided treatment interruptions. 2008 AIDS research and human retroviruses Title HIV K70R;T215F;T215Y 37;45;45 41;52;52 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. 2008 Journal of clinical virology Title HIV I50L 39 43 PR;PR 10;116 18;124 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. 2008 Antiviral therapy Title HIV K65R;L74V 70;76 74;80 RT 97 99 18507398 Impact of the enfuvirtide resistance mutation N43D and the associated baseline polymorphism E137K on peptide sensitivity and six-helix bundle structure. Impact of the enfuvirtide resistance mutation N43D and the associated baseline polymorphism E137K on peptide sensitivity and six-helix bundle structure. 2008 Biochemistry Title HIV E137K;N43D 92;46 97;50 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. 2008 Journal of acquired immune deficiency syndromes (1999) Title HIV G48E 37 41 PR 62 70 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. 2008 The Journal of biological chemistry Title HIV A360V;N348I 38;28 43;33 RT 53 74 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. 2008 Protein science Title HIV I47A 41 45 PR 105 113 18573290 Pathogenicity and immunogenicity of recombinant Tiantan Vaccinia Virus with deleted C12L and A53R genes. Pathogenicity and immunogenicity of recombinant Tiantan Vaccinia Virus with deleted C12L and A53R genes. 2008 Vaccine Title HIV A53R;C12L 93;84 97;88 18600296 False I50V resistance readings of HIV isolates: co-amplification of NASBA HIV-1 RNA QT internal calibrators and HIV-1 patient isolates may lead to a false I50V mutation resistance reading in genotypic tests. False I50V resistance readings of HIV isolates: co-amplification of NASBA HIV-1 RNA QT internal calibrators and HIV-1 patient isolates may lead to a false I50V mutation resistance reading in genotypic tests. 2008 Archives of virology Title HIV I50V;I50V 6;155 10;159 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. 2008 Journal of acquired immune deficiency syndromes (1999) Title HIV A62V;K65R;S68G 4;120;13 8;124;17 RT 37 58 18692068 Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease. Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease. 2008 Journal of molecular biology Title HIV I84V 86 94 PR 111 119 18728003 Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors". Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors". 2008 The Journal of biological chemistry Title HIV M184V;Y115F 10;20 15;25 RT;RT 35;100 56;121 18771059 Effect of tenofovir subtraction on HIV plasma viraemia, CD4+ T-cell count and resistance in a patient with baseline K65R and M184V mutations. Effect of tenofovir subtraction on HIV plasma viraemia, CD4+ T-cell count and resistance in a patient with baseline K65R and M184V mutations. 2008 Antiviral therapy Title HIV K65R;M184V 116;125 120;130 18786939 Detection of low-frequency K103N mutants after unstructured discontinuation of efavirenz in the presence of the CYP2B6 516 TT polymorphism. Detection of low-frequency K103N mutants after unstructured discontinuation of efavirenz in the presence of the CYP2B6 516 TT polymorphism. 2008 The Journal of antimicrobial chemotherapy Title HIV K103N 27 32 18818198 The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation. The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation. 2008 The Journal of biological chemistry Title HIV V75I 73 77 RT 78 99 18838591 Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. 2008 Antimicrobial agents and chemotherapy Title HIV K65R 96 100 18974494 High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome. High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome. 2008 Indian journal of medical microbiology Title HIV K103N 22 27 AIDS 85 119 19019971 In vivo fitness cost of the M184V mutation in multidrug-resistant human immunodeficiency virus type 1 in the absence of lamivudine. In vivo fitness cost of the M184V mutation in multidrug-resistant human immunodeficiency virus type 1 in the absence of lamivudine. 2009 Journal of virology Title HIV M184V 28 33 19032103 Sensitivity of phenotypic susceptibility analyses for nonthymidine nucleoside analogues conferred by K65R or M184V in mixtures with wild-type HIV-1. Sensitivity of phenotypic susceptibility analyses for nonthymidine nucleoside analogues conferred by K65R or M184V in mixtures with wild-type HIV-1. 2009 The Journal of infectious diseases Title HIV K65R;M184V 101;109 105;114 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. 2009 Infection, genetics and evolution Title HIV K65R 21 25 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. 2009 AIDS (London, England) Title HIV L74I;L74V 59;68 63;72 HIV infections 97 111 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. 2008 Biochemistry Title HIV Q509L 21 69 RT 108 129 19073730 Template usage is responsible for the preferential acquisition of the K65R reverse transcriptase mutation in subtype C variants of human immunodeficiency virus type 1. Template usage is responsible for the preferential acquisition of the K65R reverse transcriptase mutation in subtype C variants of human immunodeficiency virus type 1. 2009 Journal of virology Title HIV K65R 70 74 RT 75 96 19073742 Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D. Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D. 2009 Journal of virology Title HIV A92E;G94D 111;120 115;124 Capsid 89 95 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. 2009 Nucleic acids research Title HIV G140S;Q148H 4;120 9;125 IN 26 36 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. 2009 Clinical infectious diseases Title HIV K103N 20 25 NNRTI 108 143 19138518 Investigation on the role of the tetrazole in the binding of thiotetrazolylacetanilides with HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. Investigation on the role of the tetrazole in the binding of thiotetrazolylacetanilides with HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. 2009 Bioorganic & medicinal chemistry letters Title HIV K103N;Y181C 113;119 118;124 RT 139 161 19171798 Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection. Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection. 2009 Antimicrobial agents and chemotherapy Title HIV K103N 65 70 HIV infections 106 127 19178153 Potent inhibitors of HIV-1 integrase display a two-step, slow-binding inhibition mechanism which is absent in a drug-resistant T66I/M154I mutant. Potent inhibitors of HIV-1 integrase display a two-step, slow-binding inhibition mechanism which is absent in a drug-resistant T66I/M154I mutant. 2009 Biochemistry Title HIV M154I;T66I 132;127 137;131 IN 27 36 19193782 The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. 2009 Journal of virology Title HIV I132M 106 111 NNRTI 40 75 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. 2009 Retrovirology Title HIV K65R;K65R;K65R;K65R;M184V;M184V 15;24;15;24;29;29 19;28;19;28;34;34 RT 35 56 19219633 Drug-resistant molecular mechanism of CRF01_AE HIV-1 protease due to V82F mutation. Drug-resistant molecular mechanism of CRF01_AE HIV-1 protease due to V82F mutation. 2009 Journal of computer-aided molecular design Title HIV V82F 69 73 PR 53 61 19223637 Apricitabine does not select additional drug resistance mutations in tissue culture in human immunodeficiency virus type 1 variants containing K65R, M184V, or M184V plus thymidine analogue mutations. Apricitabine does not select additional drug resistance mutations in tissue culture in human immunodeficiency virus type 1 variants containing K65R, M184V, or M184V plus thymidine analogue mutations. 2009 Antimicrobial agents and chemotherapy Title HIV K65R;M184V;M184V 143;149;159 147;154;164 19223644 Human immunodeficiency virus type 1 isolates with the reverse transcriptase (RT) mutation Q145M retain nucleoside and nonnucleoside RT inhibitor susceptibility. Human immunodeficiency virus type 1 isolates with the reverse transcriptase (RT) mutation Q145M retain nucleoside and nonnucleoside RT inhibitor susceptibility. 2009 Antimicrobial agents and chemotherapy Title HIV Q145M 90 95 RT;RT;RT 54;77;132 75;79;134 19282784 HIV-1 transmission cluster with T215D revertant mutation among newly diagnosed patients from the Basque Country, Spain. HIV-1 transmission cluster with T215D revertant mutation among newly diagnosed patients from the Basque Country, Spain. 2009 Journal of acquired immune deficiency syndromes (1999) Title HIV T215D 32 37 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. 2009 Journal of chemical information and modeling Title HIV Y181C 27 32 RT 61 82 19414275 Bridge water mediates nevirapine binding to wild type and Y181C HIV-1 reverse transcriptase--evidence from molecular dynamics simulations and MM-PBSA calculations. Bridge water mediates nevirapine binding to wild type and Y181C HIV-1 reverse transcriptase--evidence from molecular dynamics simulations and MM-PBSA calculations. 2009 Journal of molecular graphics & modelling Title HIV Y181C 58 63 RT 70 91 19433556 Detection and quantification of minor human immunodeficiency virus type 1 variants harboring K103N and Y181C resistance mutations in subtype A and D isolates by allele-specific real-time PCR. Detection and quantification of minor human immunodeficiency virus type 1 variants harboring K103N and Y181C resistance mutations in subtype A and D isolates by allele-specific real-time PCR. 2009 Antimicrobial agents and chemotherapy Title HIV K103N;Y181C 93;103 98;108 19487156 Mutation L33M in the HR1 region of HIV-1 gp41 may play a role in T20 resistance. Mutation L33M in the HR1 region of HIV-1 gp41 may play a role in T20 resistance. 2009 Journal of clinical virology Title HIV L33M 9 13 gp41 41 45 19493444 Competitive capacity of HIV-1 strains carrying M184I or Y181I drug-resistant mutations. Competitive capacity of HIV-1 strains carrying M184I or Y181I drug-resistant mutations. 2009 Chinese medical journal Title HIV M184I;Y181I 47;56 52;61 19509419 Mechanisms associated with HIV-1 resistance to acyclovir by the V75I mutation in reverse transcriptase. Mechanisms associated with HIV-1 resistance to acyclovir by the V75I mutation in reverse transcriptase. 2009 The Journal of biological chemistry Title HIV V75I 64 68 RT 81 102 19523982 Sensitive detection of the K103N non-nucleoside reverse transcriptase inhibitor resistance mutation in treatment-naive HIV-1 infected individuals by rolling circle amplification. Sensitive detection of the K103N non-nucleoside reverse transcriptase inhibitor resistance mutation in treatment-naive HIV-1 infected individuals by rolling circle amplification. 2009 Journal of virological methods Title HIV K103N 27 32 NNRTI 33 69 HIV infections 119 133 19563238 Modulation of K65R selection by zidovudine inclusion: analysis of HIV resistance selection in subjects with virologic failure receiving once-daily abacavir/lamivudine/zidovudine and tenofovir DF (study COL40263). Modulation of K65R selection by zidovudine inclusion: analysis of HIV resistance selection in subjects with virologic failure receiving once-daily abacavir/lamivudine/zidovudine and tenofovir DF (study COL40263). 2009 AIDS research and human retroviruses Title HIV K65R 14 18 19625211 Mutation N155H in HIV-2 integrase confers high phenotypic resistance to raltegravir and impairs replication capacity. Mutation N155H in HIV-2 integrase confers high phenotypic resistance to raltegravir and impairs replication capacity. 2009 Journal of clinical virology Title HIV N155H 9 14 IN 24 33 19626612 Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. 2009 Journal of medical virology Title HIV K65R 18 22 RT 34 55 19629548 Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. 2010 Journal of molecular modeling Title HIV D30N;I50V 43;52 47;56 PR 66 74 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. 2009 Journal of acquired immune deficiency syndromes (1999) Title HIV K65R 66 70 HIV infections 35 47 19681953 Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy. Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy. 2010 Clinical microbiology and infection Title HIV K103N 80 85 RT 58 79 19704127 Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine. Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine. 2009 Antimicrobial agents and chemotherapy Title HIV G190A;Y181C 93;103 98;108 RT 48 69 19704131 Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. 2009 Antimicrobial agents and chemotherapy Title HIV P119S;T165A 84;94 89;99 RT 52 73 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. 2009 The Journal of antimicrobial chemotherapy Title HIV T74S 9 13 PR 39 48 19720046 Resistance mechanism revealed by crystal structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S. Resistance mechanism revealed by crystal structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S. 2009 Biochemical and biophysical research communications Title HIV N88D;N88S 126;135 130;139 PR 93 101 19764886 Signature nucleotide polymorphisms at positions 64 and 65 in reverse transcriptase favor the selection of the K65R resistance mutation in HIV-1 subtype C. Signature nucleotide polymorphisms at positions 64 and 65 in reverse transcriptase favor the selection of the K65R resistance mutation in HIV-1 subtype C. 2009 The Journal of infectious diseases Title HIV K65R 110 114 RT 61 82 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. 2009 The Journal of biological chemistry Title HIV V75I 45 49 RT 59 80 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. 2009 The Journal of biological chemistry Title HIV K65R 37 41 RT 60 81 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. 2009 PloS one Title HIV Q65R;R77Q 92;101 96;105 Vpr;Vpr 64;123 67;126 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. 2009 Journal of medical virology Title HIV K103N 92 97 19910081 Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations. Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations. 2010 European journal of medicinal chemistry Title HIV I50V;I84V;V82A 78;92;83 82;96;87 PR 116 124 19995921 Development of an allele-specific PCR for detection of the K65R resistance mutation in patients infected with subtype C human immunodeficiency virus type 1. Development of an allele-specific PCR for detection of the K65R resistance mutation in patients infected with subtype C human immunodeficiency virus type 1. 2010 Antimicrobial agents and chemotherapy Title HIV K65R 59 63 HIV infections 110 155 20009920 Sensitivity of V75I HIV-1 reverse transcriptase mutant selected in vitro by acyclovir to anti-HIV drugs. Sensitivity of V75I HIV-1 reverse transcriptase mutant selected in vitro by acyclovir to anti-HIV drugs. 2010 AIDS (London, England) Title HIV V75I 15 19 RT 26 47 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. 2010 AIDS (London, England) Title HIV N348I 0 5 RT 15 36 20032547 Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina. Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina. 2009 Antiviral therapy Title HIV K103N;M184V 54;64 59;69 20050672 Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile. Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile. 2010 Journal of medicinal chemistry Title HIV Y181C 39 44 20054099 Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. 2010 Antiviral chemistry & chemotherapy Title HIV K65R 55 59 20055586 Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41 heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*). Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41 heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*). 2010 AIDS research and human retroviruses Title HIV N43T;N44K;V38M 60;65;51 64;69;55 gp41 77 81 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. 2010 Retrovirology Title HIV T477A 13 18 RT;GagPol;RT;RT 28;114;51;97 49;121;53;99 20124001 Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. 2010 Antimicrobial agents and chemotherapy Title HIV V106I;V179D 15;25 20;30 RT 92 113 20124005 International cohort analysis of the antiviral activities of zidovudine and tenofovir in the presence of the K65R mutation in reverse transcriptase. International cohort analysis of the antiviral activities of zidovudine and tenofovir in the presence of the K65R mutation in reverse transcriptase. 2010 Antimicrobial agents and chemotherapy Title HIV K65R 109 113 RT 126 147 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. 2010 AIDS (London, England) Title HIV N348I 0 5 RT 9 30 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. 2010 AIDS (London, England) Title HIV Q148R 28 33 IN;IN 18;86 27;95 HIV infections 55 67 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. 2010 The Journal of infectious diseases Title HIV M184V;N348I 105;96 110;101 RT 120 141 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. 2009 HIV therapy Title HIV K65R 4 8 RT 27 48 20195662 Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease. Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease. 2010 Journal of molecular modeling Title HIV I54V;V82A 24;15 28;19 PR 94 102 20231447 Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution. Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution. 2010 Proc Natl Acad Sci U S A Title HIV L669S 67 72 gp41 32 36 20307579 Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. 2010 Antiviral research Title HIV K103N 124 148 RT 87 108 20308384 The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. 2010 Antimicrobial agents and chemotherapy Title HIV M230L 4 9 NNRTI;RT 10;85 45;106 20377421 Short communication: Molecular epidemiology of HIV type 1 in the Republic of Dagestan, Russian Federation: virtually uniform circulation of subtype A, former Soviet Union variant, with predominance of the V77I(PR) subvariant. Short communication: Molecular epidemiology of HIV type 1 in the Republic of Dagestan, Russian Federation: virtually uniform circulation of subtype A, former Soviet Union variant, with predominance of the V77I(PR) subvariant. 2010 AIDS research and human retroviruses Title HIV V77I 205 209 PR 210 212 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. 2010 Antiviral therapy Title HIV N348I 54 59 20432620 Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. 2010 Die Pharmazie Title HIV K90R 23 27 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. 2010 PloS one Title HIV Y143C;Y143R 30;30 37;37 IN 10 19 20455467 [CD4+ and CD8+ T-lymphocyte counts in human immunodeficiency virus type 1 subtype A-infected patients carrying mutations V77I in protease and/or A62V in reverse transcriptase]. [CD4+ and CD8+ T-lymphocyte counts in human immunodeficiency virus type 1 subtype A-infected patients carrying mutations V77I in protease and/or A62V in reverse transcriptase]. 2010 Voprosy virusologii Title HIV A62V;V77I 145;121 149;125 RT;PR 153;129 174;137 20471372 Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex. Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex. 2010 Biochemical and biophysical research communications Title HIV C95F;G48V 81;76 85;80 PR 101 109 20530477 N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. 2010 The Journal of biological chemistry Title HIV N348I 0 5 RT 15 36 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. 2010 Journal of molecular biology Title HIV K65A;K65R 9;0 13;4 RT;Pol 37;67 58;77 20541446 Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. 2010 Journal of molecular graphics & modelling Title HIV D30N 64 68 PR 24 32 20587857 HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. 2010 Antiviral therapy Title HIV K103N;L100I;L74V 118;124;134 123;129;138 20600301 Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R. Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R. 2010 The Journal of infection Title HIV K65R 148 152 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. 2010 Virology Title HIV M184I 32 37 RT 44 65 20713171 Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors. Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors. 2010 Microbes and infection Title HIV A371V;G335D 60;50 65;55 RT;RT;RT 141;164;200 162;166;202 20805393 Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. 2010 Antimicrobial agents and chemotherapy Title HIV L76V 87 91 PR;PR 46;110 54;118 20852269 Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. 2010 The Journal of antimicrobial chemotherapy Title HIV K103N;M230L 90;100 95;105 NNRTI 33 69 20876531 The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. 2010 The Journal of biological chemistry Title HIV N348I 4 9 RT 56 77 20922443 3,4,5-Trisubstituted-1,2,4-4H-triazoles as WT and Y188L mutant HIV-1 non-nucleoside reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses. 3,4,5-Trisubstituted-1,2,4-4H-triazoles as WT and Y188L mutant HIV-1 non-nucleoside reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses. 2011 Journal of molecular modeling Title HIV Y188L 50 55 NNRTI 69 105 21054750 Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. 2011 HIV medicine Title HIV M184V 89 94 HIV infections 60 74 21056001 Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients. Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients. 2011 Journal of clinical virology Title HIV K103N;K65R;M184V 45;39;56 50;43;61 HIV infections 104 118 21056575 Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. 2011 Journal of molecular biology Title HIV A62V;F61A 30;21 34;25 RT 69 90 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. 2009 Journal of medical case reports Title HIV K103N 38 43 21135184 Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes. Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes. 2011 Antimicrobial agents and chemotherapy Title HIV E138K 24 29 RT 59 80 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. 2011 AIDS research and human retroviruses Title HIV L10I 24 28 PR;PR 15;101 23;109 21157296 Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. 2011 AIDS (London, England) Title HIV K103N 17 22 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. 2011 PloS one Title HIV Q151M;K70Q 46;0 51;4 RT 65 86 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. 2011 Virology journal Title HIV K65R;K65R;L74I 100;152;157 104;156;161 RT 48 69 21257741 Detection of low-level K65R variants in nucleoside reverse transcriptase inhibitor-naive chronic and acute HIV-1 subtype C infections. Detection of low-level K65R variants in nucleoside reverse transcriptase inhibitor-naive chronic and acute HIV-1 subtype C infections. 2011 The Journal of infectious diseases Title HIV K65R 23 27 NRTI 40 72 21282419 Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1. Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1. 2011 Antimicrobial agents and chemotherapy Title HIV N348I 14 19 NNRTI;RT 63;38 98;59 21285456 Predictors for the emergence of the 2 multi-nucleoside/nucleotide resistance mutations 69 insertion and Q151M and their impact on clinical outcome in the Swiss HIV cohort study. Predictors for the emergence of the 2 multi-nucleoside/nucleotide resistance mutations 69 insertion and Q151M and their impact on clinical outcome in the Swiss HIV cohort study. 2011 The Journal of infectious diseases Title HIV Q151M 104 109 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? 2011 AIDS research and therapy Title HIV L76V 4 8 PR;PR 27;90 35;98 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? BACKGROUND: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. 2011 AIDS research and therapy Title HIV L76V 4 8 PR;PR;PR 27;90;233 35;98;241 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage. 2011 AIDS research and therapy Title HIV L76V 4 8 21338625 Within-host co-evolution of Gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case. Within-host co-evolution of Gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case. 2011 Antiviral research Title HIV D30N;N88D;P453L 51;56;32 55;60;37 PR;PR;Gag 42;108;28 50;116;31 21371237 Increased detection of the HIV-1 reverse transcriptase M184V mutation using mutation-specific minority assays in a UK surveillance study suggests evidence of unrecognized transmitted drug resistance. Increased detection of the HIV-1 reverse transcriptase M184V mutation using mutation-specific minority assays in a UK surveillance study suggests evidence of unrecognized transmitted drug resistance. 2011 HIV medicine Title HIV M184V 55 60 RT 33 54 21402840 Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. 2011 Antimicrobial agents and chemotherapy Title HIV Q151L 52 57 RT 76 97 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. 2011 Biochemistry Title HIV L76V 4 8 PR 100 108 21453185 Characterization of HIV type 1 subtype C protease gene: selection of L63P mutation in protease inhibitor-naive Indian patients. Characterization of HIV type 1 subtype C protease gene: selection of L63P mutation in protease inhibitor-naive Indian patients. 2011 AIDS research and human retroviruses Title HIV L63P 69 73 PR;PR 41;86 49;94 21459401 Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. 2011 Virology Title HIV K65N;K65R 31;103 35;107 RT;RT 0;127 21;129 21473930 Selection of HLA-B57-associated Gag A146P mutant by HLA-B *48:01-restricted Gag140-147-specific CTLs in chronically HIV-1-infected Japanese. Selection of HLA-B57-associated Gag A146P mutant by HLA-B*48:01-restricted Gag140-147-specific CTLs in chronically HIV-1-infected Japanese. 2011 Microbes and infection Title HIV A146P 36 41 Gag;Gag 32;75 35;78 HIV infections 115 129 21498149 Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. 2011 HIV clinical trials Title HIV M184I;M184V 25;25 32;32 NNRTI;NRTI 167;152 172;157 21537677 The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors. The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors. 2011 Memorias do Instituto Oswaldo Cruz Title HIV D30N 60 64 PR 115 123 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. 2011 Retrovirology Title HIV Q151M 72 77 RT 23 44 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. 2011 Antimicrobial agents and chemotherapy Title HIV T97A;Y143C;Y143R 125;42;42 129;49;49 IN 32 41 21636271 Enantioselective binding of second generation pyrrolobenzoxazepinones to the catalytic ternary complex of HIV-1 RT wild-type and L100I and K103N drug resistant mutants. Enantioselective binding of second generation pyrrolobenzoxazepinones to the catalytic ternary complex of HIV-1 RT wild-type and L100I and K103N drug resistant mutants. 2011 Bioorganic & medicinal chemistry letters Title HIV K103N;L100I 139;129 144;134 RT 112 114 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. 2011 PloS one Title HIV K65R 55 59 RT 60 81 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. 2011 PloS one Title HIV K103N 30 35 21750100 Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. 2011 The Journal of antimicrobial chemotherapy Title HIV M184V 29 34 HIV infections 63 84 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. 2011 PloS one Title HIV K103N 25 30 21844300 A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. 2011 The Journal of infectious diseases Title HIV A376S 0 5 RT 43 64 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. 2011 Journal of virology Title HIV E138K;M184I;M184V 20;153;153 25;160;160 RT 44 65 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. 2011 Journal of the American Chemical Society Title HIV Y181C 60 69 RT 85 106 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. 2011 Retrovirology Title HIV G140S;N155H;Q148R;Y143C 0;16;6;88 5;21;11;93 IN 45 54 21875140 Combined approach using ligand efficiency, cross-docking, and antitarget hits for wild-type and drug-resistant Y181C HIV-1 reverse transcriptase. Combined approach using ligand efficiency, cross-docking, and antitarget hits for wild-type and drug-resistant Y181C HIV-1 reverse transcriptase. 2011 Journal of chemical information and modeling Title HIV Y181C 111 116 RT 123 144 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. 2011 Antiviral therapy Title HIV K65R 75 79 RT 44 65 21933786 The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype. The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype. 2011 The Journal of antimicrobial chemotherapy Title HIV G118R 20 25 IN 10 19 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. 2011 AIDS (London, England) Title HIV N155H;Q148R 81;71 86;76 IN 51 60 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. 2012 Journal of acquired immune deficiency syndromes (1999) Title HIV E138K;M184I 60;32 65;37 RT 10 31 22027876 Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M. Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M. 2012 Journal of acquired immune deficiency syndromes (1999) Title HIV Q151M 118 123 22078905 Detection and quantification of the K103N mutation in HIV reverse transcriptase by pyrosequencing. Detection and quantification of the K103N mutation in HIV reverse transcriptase by pyrosequencing. 2012 Diagnostic microbiology and infectious disease Title HIV K103N 36 41 RT 58 79 22093289 Emergence of an HIV-1 cluster harbouring the major protease L90M mutation among treatment-naive patients in Tel Aviv, Israel. Emergence of an HIV-1 cluster harbouring the major protease L90M mutation among treatment-naive patients in Tel Aviv, Israel. 2012 HIV medicine Title HIV L90M 60 64 PR 51 59 22095519 Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates. Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates. 2011 Antiviral chemistry & chemotherapy Title HIV K103N;Y181I 70;80 75;85 RT 99 120 22138483 E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. 2012 Antiviral research Title HIV E17A 0 4 Vpr 23 26 22188777 Genetic and structural analysis of HIV-1 Rev responsive element related to V38A and T18A enfuvirtide resistance mutations. Genetic and structural analysis of HIV-1 Rev responsive element related to V38A and T18A enfuvirtide resistance mutations. 2012 Intervirology Title HIV T18A;V38A 84;75 88;79 Rev 41 44 22200907 Control of M184V HIV-1 mutants by CD8 T-cell responses. Control of M184V HIV-1 mutants by CD8 T-cell responses. 2012 Medical microbiology and immunology Title HIV M184V 11 16 22205735 Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. 2012 Journal of virology Title HIV R263K 24 29 IN;IN 48;117 57;126 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. 2012 The journal of physical chemistry. B Title HIV A71V;I50L;I50V 36;31;15 40;35;19 PR 59 67 22301145 Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. 2012 Journal of virology Title HIV N74D 52 56 Capsid 36 42 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. 2012 Retrovirology Title HIV N140I 21 26 gp41 40 44 22340881 [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. 2011 Zhonghua liu xing bing xue za zhi Title HIV N348I 52 57 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. 2012 PloS one Title HIV A360V 45 50 RT 94 115 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. 2012 Journal of virology Title HIV M184V 157 162 RT 120 141 22490797 [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. 2012 Zhonghua yi xue za zhi Title HIV H221Y 43 48 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. 2012 Antiviral research Title HIV F121Y 34 39 22606344 Association of enhanced HIV-1 neutralization by a single Y681H substitution in gp41 with increased gp120-CD4 interaction and macrophage infectivity. Association of enhanced HIV-1 neutralization by a single Y681H substitution in gp41 with increased gp120-CD4 interaction and macrophage infectivity. 2012 PloS one Title HIV Y681H 57 62 gp120;gp41 99;79 104;83 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. 2012 PloS one Title HIV K65R 0 4 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. 2012 Clinical infectious diseases Title HIV N348I 22 27 RT;RT 47;127 68;148 22623801 Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. 2012 Journal of virology Title HIV E138K;M184I 96;106 101;111 RT 131 152 22695298 E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure. E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure. 2012 AIDS (London, England) Title HIV M184I;E138K 10;0 15;5 RT 35 56 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. 2012 AIDS (London, England) Title HIV K65R 13 17 HIV infections 75 88 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. 2012 Retrovirology Title HIV K65R 56 60 RT 61 82 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. 2012 Retrovirology Title HIV L210W;M41L;R284K;T215Y 174;168;118;184 179;172;123;189 RT 83 104 22906365 The prevalence of transmitted drug resistance in newly diagnosed HIV-infected individuals in Croatia: the role of transmission clusters of men who have sex with men carrying the T215S surveillance drug resistance mutation. The prevalence of transmitted drug resistance in newly diagnosed HIV-infected individuals in Croatia: the role of transmission clusters of men who have sex with men carrying the T215S surveillance drug resistance mutation. 2013 AIDS research and human retroviruses Title HIV T215S 178 183 HIV infections 65 77 22914581 Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? 2013 AIDS (London, England) Title HIV K103N 69 74 22914581 Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? We report long-term virologic response to etravirine and tenofovir/emtricitabine in four HIV-1-infected patients who had prior standard genotypic resistance testing showing an isolated K103N mutation (three acquired, one transmitted). 2013 AIDS (London, England) Title HIV K103N 69 74 HIV infections 174 188 22914581 Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation. 2013 AIDS (London, England) Title HIV K103N 69 74 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. 2012 Journal of virology Title HIV E138K;Y181C 56;46 61;51 RT 81 102 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. 2013 HIV medicine Title HIV N155H 35 40 IN 25 34 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. 2013 The Journal of antimicrobial chemotherapy Title HIV K65R 61 65 23123544 Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. 2013 Microbes and infection Title HIV Q110D 7 12 Gag;Capsid 0;4 3;6 23183438 HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir. HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir. 2013 Antimicrobial agents and chemotherapy Title HIV K65R 76 80 RT 45 66 23230246 Baseline-transmitted V106V/I/M non-nucleoside reverse transcriptase inhibitor resistance in HIV-1 subtype B infection. Baseline-transmitted V106V/I/M non-nucleoside reverse transcriptase inhibitor resistance in HIV-1 subtype B infection. 2012 BMJ case reports Title HIV V106I;V106M;V106V 21;21;21 30;30;30 NNRTI 31 67 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Title HIV N348I 86 91 RT;RT 34;137 55;158 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. 2013 Bioorganic & medicinal chemistry letters Title HIV Y181C 102 107 RT 69 90 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. 2012 Journal of the International AIDS Society Title HIV K65R 30 34 23325683 Cyclophilin A-dependent restriction to capsid N121K mutant human immunodeficiency virus type 1 in a broad range of cell lines. Cyclophilin A-dependent restriction to capsid N121K mutant human immunodeficiency virus type 1 in a broad range of cell lines. 2013 Journal of virology Title HIV N121K 46 51 Capsid 39 45 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. 2013 PloS one Title HIV L76V 19 23 PR 35 43 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. 2013 The international journal of biochemistry & cell biology Title HIV S138A 27 32 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. 2013 Retrovirology Title HIV V86M 4 8 Capsid 27 33 23522564 Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled-coil domain regulates 6-helical bundle formation. Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled-coil domain regulates 6-helical bundle formation. 2013 Bioorganic & medicinal chemistry letters Title HIV I646K 38 47 gp41 60 64 23535575 L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness. L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness. 2013 The Journal of general virology Title HIV G190S;K101E;K103N;L100I;L74V 155;149;139;133;0 160;154;144;138;4 NNRTI;RT 71;19 107;40 23541840 Detection of HIV-1 minority variants containing the K103N drug-resistance mutation using a simple method to amplify RNA targets (SMART). Detection of HIV-1 minority variants containing the K103N drug-resistance mutation using a simple method to amplify RNA targets (SMART). 2013 The Journal of molecular diagnostics Title HIV K103N 52 57 23562659 Improvement of the oligonucleotide ligation assay for detection of the M184V drug-resistant mutation in patients infected with human immunodeficiency virus type 1 subtype CRF01_AE. Improvement of the oligonucleotide ligation assay for detection of the M184V drug-resistant mutation in patients infected with human immunodeficiency virus type 1 subtype CRF01_AE. 2013 Journal of virological methods Title HIV M184V 71 76 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. 2013 Antimicrobial agents and chemotherapy Title HIV M184I 100 105 NNRTI;RT 153;46 188;67 23615903 The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. 2013 The Journal of biological chemistry Title HIV A128T 4 9 IN 126 135 23633402 Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques. Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques. 2013 The Journal of infectious diseases Title HIV K65R 179 183 23707381 A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication. A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication. 2013 Journal of molecular biology Title HIV I107T 34 39 Vif 22 25 23731270 Transmission network of an HIV type 1 strain with K103N in young Belgian patients from different risk groups. Transmission network of an HIV type 1 strain with K103N in young Belgian patients from different risk groups. 2013 AIDS research and human retroviruses Title HIV K103N 50 55 23749952 Evolution of the K65R, K103N and M184V/I reverse transcriptase mutations in HIV-1-infected patients experiencing virological failure between 2005 and 2010. Evolution of the K65R, K103N and M184V/I reverse transcriptase mutations in HIV-1-infected patients experiencing virological failure between 2005 and 2010. 2013 The Journal of antimicrobial chemotherapy Title HIV K103N;K65R;M184I;M184V 23;17;33;33 28;21;40;40 RT 41 62 HIV infections 76 90 23749954 The preferential selection of K65R in HIV-1 subtype C is attenuated by nucleotide polymorphisms at thymidine analogue mutation sites. The preferential selection of K65R in HIV-1 subtype C is attenuated by nucleotide polymorphisms at thymidine analogue mutation sites. 2013 The Journal of antimicrobial chemotherapy Title HIV K65R 30 34 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. 2013 The Journal of antimicrobial chemotherapy Title HIV K65E 66 70 NRTI;RT 110;37 145;58 HIV infections 75 89 23804564 Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S. Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S. 2013 The Journal of general virology Title HIV G190S;K101E 135;129 140;134 NNRTI;RT 84;0 120;21 23834142 A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. 2013 Journal of chemical information and modeling Title HIV I50V 151 155 PR 121 129 23856772 Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. 2013 Antimicrobial agents and chemotherapy Title HIV E138K 50 55 RT 74 95 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. 2013 Antimicrobial agents and chemotherapy Title HIV K101E 12 17 NNRTI;RT 101;40 136;61 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. 2013 PloS one Title HIV L90M 109 113 PR;PR 54;70 62;78 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. 2013 PloS one Title HIV K65R;Q151M 28;18 32;23 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. 2013 Antimicrobial agents and chemotherapy Title HIV G118R 36 41 IN 101 110 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. 2014 Journal of virology Title HIV E138K;N348I 153;31 158;36 RT 46 67 24419343 Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine. Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine. 2014 Antimicrobial agents and chemotherapy Title HIV E138A 45 50 RT 73 94 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. 2014 Retrovirology Title HIV M50I;R263K 4;58 8;63 IN 92 101 24657622 Raltegravir and elvitegravir-resistance mutation E92Q affects HLA-B*40:02-restricted HIV-1-specific CTL recognition. Raltegravir and elvitegravir-resistance mutation E92Q affects HLA-B*40:02-restricted HIV-1-specific CTL recognition. 2014 Microbes and infection Title HIV E92Q 49 53 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. 2014 Antiviral research Title HIV H208Y;L210W;M41L;T215Y 38;94;88;104 43;99;92;109 RT 123 144 24738660 Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation acquired during prior nonnucleoside reverse transcriptase inhibitor therapy. Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation acquired during prior nonnucleoside reverse transcriptase inhibitor therapy. 2014 HIV medicine Title HIV K103N 101 106 NNRTI 138 173 HIV infections 60 74 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. 2014 Antiviral research Title HIV E138A 0 5 RT 15 36 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. 2014 Antimicrobial agents and chemotherapy Title HIV W153L 15 20 RT;RT 41;130 62;151 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. 2014 BMC infectious diseases Title HIV H221Y;Y181C 23;10 28;15 RT 56 77 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. 2014 The Journal of antimicrobial chemotherapy Title HIV E138K;R263K 12;21 17;26 IN;IN 34;123 43;132 24931725 An integrated molecular dynamics, principal component analysis and residue interaction network approach reveals the impact of M184V mutation on HIV reverse transcriptase resistance to lamivudine. An integrated molecular dynamics, principal component analysis and residue interaction network approach reveals the impact of M184V mutation on HIV reverse transcriptase resistance to lamivudine. 2014 Molecular bioSystems Title HIV M184V 126 131 RT 148 169 24938655 Co-evolution of compensatory mutation K43E with mutation M41L in long-term HIV antiretroviral treatment. Co-evolution of compensatory mutation K43E with mutation M41L in long-term HIV antiretroviral treatment. 2014 Current HIV research Title HIV K43E;M41L 38;57 42;61 25006240 Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France. Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France. 2014 The Journal of antimicrobial chemotherapy Title HIV E138A 63 68 25036184 Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients. Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients. 2014 AIDS (London, England) Title HIV K103N;Y181C 37;47 42;52 25063804 The HIV-1 integrase mutant R263A/K264A is 2-fold defective for TRN-SR2 binding and viral nuclear import. The HIV-1 integrase mutant R263A/K264A is 2-fold defective for TRN-SR2 binding and viral nuclear import. 2014 The Journal of biological chemistry Title HIV K264A;R263A 33;27 38;32 IN 10 19 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. 2014 The protein journal Title HIV M184V;N348I 43;37 48;42 25281399 Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. 2015 The Journal of antimicrobial chemotherapy Title HIV N155H 88 93 25348535 The R262K substitution combined with H51Y in HIV-1 subtype B integrase confers low-level resistance against dolutegravir. The R262K substitution combined with H51Y in HIV-1 subtype B integrase confers low-level resistance against dolutegravir. 2015 Antimicrobial agents and chemotherapy Title HIV H51Y;R262K 37;4 41;9 IN 61 70 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. 2015 Journal of virology Title HIV K65R;Q151M;V111I 105;114;9 109;119;14 RT 24 45 25373632 Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase. Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase. 2014 Interdisciplinary sciences, computational life sciences Title HIV E92Q;N155H 59;64 63;69 IN 110 119 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. 2014 Journal of the International AIDS Society Title HIV R263K 4 9 IN 26 35 25414202 G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. 2015 The Journal of antimicrobial chemotherapy Title HIV F121Y;G118R 10;0 15;5 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. 2014 Retrovirology Title HIV H171T 17 22 IN 139 148 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. 2014 Molecular therapy. Nucleic acids Title HIV D167H 123 128 IN 27 36 25487655 Structural Basis of Why Nelfinavir-Resistant D30N Mutant of HIV-1 Protease Remains Susceptible to Saquinavir. Structural Basis of Why Nelfinavir-Resistant D30N Mutant of HIV-1 Protease Remains Susceptible to Saquinavir. 2015 Chemical biology & drug design Title HIV D30N 45 49 PR 66 74 25488402 Modulation of HIV protease flexibility by the T80N mutation. Modulation of HIV protease flexibility by the T80N mutation. 2015 Proteins Title HIV T80N 46 50 PR 18 26 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. 2015 Biochemistry Title HIV G48T;L89M 107;116 115;124 PR 75 83 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. 2014 PloS one Title HIV W427S 33 38 Env 9 17 25552724 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. 2015 Journal of virology Title HIV E138K;G118R;H51Y 45;28;35 50;33;39 IN 105 114 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. 2015 Journal of molecular graphics & modelling Title HIV M46L;V32I 42;33 46;37 PR 60 68 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. 2014 BMC genomics Title HIV M36I 10 14 PR 56 64 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. 2015 Journal of computer-aided molecular design Title HIV V260E 34 39 IN 74 83 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. 2015 The Journal of antimicrobial chemotherapy Title HIV D404N 18 23 RT;NNRTI 56;132 77;138 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. 2015 PloS one Title HIV K65R 23 27 25666155 Combination of the R263K and M184I/V resistance substitutions against dolutegravir and lamivudine decreases HIV replicative capacity. Combination of the R263K and M184I/V resistance substitutions against dolutegravir and lamivudine decreases HIV replicative capacity. 2015 Antimicrobial agents and chemotherapy Title HIV M184I;M184V;R263K 29;29;19 36;36;24 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. 2015 Nucleic acids research Title HIV D67N;K70R 138;147 142;151 RT 40 61 25779585 Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. 2015 Antimicrobial agents and chemotherapy Title HIV K65R 33 37 RT 125 146 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. 2015 PloS one Title HIV I559P 15 20 gp41;Env 21;119 25;127 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. 2014 AIDS research and therapy Title HIV G190A;K103N;Y181C 61;45;51 66;50;56 25956162 Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. 2015 Antiviral research Title HIV S119R 21 26 IN;INSTI 36;63 45;68 26003522 P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core. P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core. 2015 Microbes and infection Title HIV P20A 0 4 gp41 95 99 26130028 Diverse mutants of HIV RRE IIB recognize wild-type Rev ARM or Rev ARM R35G-N40V. Diverse mutants of HIV RRE IIB recognize wild-type Rev ARM or Rev ARM R35G-N40V. 2015 Journal of molecular recognition Title HIV N40V;R35G 75;70 79;74 Rev;Rev 51;62 54;65 26166507 Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization. Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization. 2016 Japanese journal of infectious diseases Title HIV M434I 43 48 gp120 75 80 26198456 Understanding the basis of I50V-induced affinity decrease in HIV-1 protease via molecular dynamics simulations using polarized force field. Understanding the basis of I50V-induced affinity decrease in HIV-1 protease via molecular dynamics simulations using polarized force field. 2015 Journal of computational chemistry Title HIV I50V 27 31 PR 67 75 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. 2015 AIDS (London, England) Title HIV R263K 4 9 IN 66 75 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. 2015 Journal of virology Title HIV N155H;R263K 43;53 48;58 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. 2015 Journal of virology Title HIV R263K;T66I 23;33 28;37 IN 72 81 26317593 A Comparative Insight into Amprenavir Resistance of Mutations V32I, G48V, I50V, I54V, and I84V in HIV-1 Protease Based on Thermodynamic Integration and MM-PBSA Methods. A Comparative Insight into Amprenavir Resistance of Mutations V32I, G48V, I50V, I54V, and I84V in HIV-1 Protease Based on Thermodynamic Integration and MM-PBSA Methods. 2015 Journal of chemical information and modeling Title HIV G48V;I50V;I54V;I84V;V32I 68;74;80;90;62 72;78;84;94;66 PR 104 112 26324274 Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase. Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase. 2015 Antimicrobial agents and chemotherapy Title HIV L210W;M41L;T215Y 65;55;48 70;59;53 RT 80 101 26351907 The double mutation L109M and R448M of HIV-1 reverse transcriptase decreases fidelity of DNA synthesis by promoting mismatch elongation. The double mutation L109M and R448M of HIV-1 reverse transcriptase decreases fidelity of DNA synthesis by promoting mismatch elongation. 2015 Biological chemistry Title HIV L109M;R448M 20;30 25;35 RT 45 66 26372484 The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. 2015 AIDS (London, England) Title HIV R263K 17 22 IN 52 61 26487915 Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance. Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance. 2015 ACS medicinal chemistry letters Title HIV K101P 64 69 RT 37 58 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. 2016 Antimicrobial agents and chemotherapy Title HIV N155H;Q148R 121;112 126;117 RT;IN 169;52 190;61 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. 2013 Journal of chemical theory and computation Title HIV A71V;G48V;G73S;I84V;L10I;L63P;V82A 148;136;154;169;130;142;160 152;140;158;173;134;146;164 PR 123 125 26610114 Study of the Conformational Dynamics of the Catalytic Loop of WT and G140A/G149A HIV-1 Integrase Core Domain Using Reversible Digitally Filtered Molecular Dynamics. Study of the Conformational Dynamics of the Catalytic Loop of WT and G140A/G149A HIV-1 Integrase Core Domain Using Reversible Digitally Filtered Molecular Dynamics. 2009 Journal of chemical theory and computation Title HIV G140A;G149A 69;75 74;80 IN 87 96 26613568 Binding Free Energy Calculations of Nine FDA-approved Protease Inhibitors Against HIV-1 Subtype C I36T upward arrowT Containing 100 Amino Acids Per Monomer. Binding Free Energy Calculations of Nine FDA-approved Protease Inhibitors Against HIV-1 Subtype C I36T T Containing 100 Amino Acids Per Monomer. 2016 Chemical biology & drug design Title HIV I36T 98 102 PR 54 62 26650686 An in-silico approach aimed to clarify the role of Y181C and K103N HIV-1 reverse transcriptase mutations versus Indole Aryl Sulphones. An in-silico approach aimed to clarify the role of Y181C and K103N HIV-1 reverse transcriptase mutations versus Indole Aryl Sulphones. 2016 Journal of molecular graphics & modelling Title HIV K103N;Y181C 61;51 66;56 RT 73 94 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. 2015 BMC bioinformatics Title HIV V77I 103 107 PR 117 125 26746222 Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD). Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD). 2016 Medical microbiology and immunology Title HIV K65R 14 18 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. 2016 The Journal of antimicrobial chemotherapy Title HIV K65R 31 35 HIV infections 64 78 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. 2016 AIDS research and human retroviruses Title HIV Q148N 0 5 IN 15 24 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. 2016 The Journal of antimicrobial chemotherapy Title HIV G118R 17 22 IN;IN 41;129 50;138 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. 2016 AIDS research and human retroviruses Title HIV L228I;Y232H 16;26 21;31 NNRTI 38 73 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. 2016 Journal of medicinal chemistry Title HIV E138K 160 165 NNRTI 12 48 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. 2016 The Journal of antimicrobial chemotherapy Title HIV E157Q;R263K 25;60 30;65 IN 40 49 27235396 The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7. The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7. 2016 The Journal of biological chemistry Title HIV K71K 43 66 Tat 10 13 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. 2016 The Journal of antimicrobial chemotherapy Title HIV E138K 32 37 RT 47 68 27352730 Expansion of the E138A mutation in newly diagnosed HIV-infected patients in Gran Canaria. Expansion of the E138A mutation in newly diagnosed HIV-infected patients in Gran Canaria. 2016 Diagnostic microbiology and infectious disease Title HIV E138A 17 22 HIV infections 51 63 27367488 The M184I/V and K65R nucleoside resistance mutations in HIV-1 prevent the emergence of resistance mutations against dolutegravir. The M184I/V and K65R nucleoside resistance mutations in HIV-1 prevent the emergence of resistance mutations against dolutegravir. 2016 AIDS (London, England) Title HIV K65R;M184I;M184V 16;4;4 20;11;11 27381400 The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity. The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity. 2016 Antimicrobial agents and chemotherapy Title HIV R953C 25 30 Pol 8 18 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. 2016 Journal of global antimicrobial resistance Title HIV A98S 45 49 RT 10 31 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. 2016 Viruses Title HIV K103N;Y181C 100;110 105;115 NNRTI 28 64 27677159 Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. 2016 AIDS (London, England) Title HIV K65K;K66K 25;34 29;38 RT 58 79 27722739 Molecular insight on the binding of NNRTI to K103N mutated HIV-1 RT: molecular dynamics simulations and dynamic pharmacophore analysis. Molecular insight on the binding of NNRTI to K103N mutated HIV-1 RT: molecular dynamics simulations and dynamic pharmacophore analysis. 2016 Molecular bioSystems Title HIV K103N 45 50 NNRTI;RT 36;65 41;67 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. 2016 Viruses Title HIV N659D 31 36 Env;Env 46;69 54;72 27900665 Use of Capillary Electrophoresis to Study the Binding Interaction of Aptamers with Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT : Studying the Binding Interaction of Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT with Aptamers by Performing the Capillary Electrophoresis. Use of Capillary Electrophoresis to Study the Binding Interaction of Aptamers with Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT : Studying the Binding Interaction of Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT with Aptamers by Performing the Capillary Electrophoresis. 2017 Applied biochemistry and biotechnology Title HIV K103N;K103N;K103N;K103N;K103N;Y181C;Y181C 120;94;191;217;94;126;223 125;99;196;222;99;131;228 RT;RT 139;236 141;238 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. 2017 PloS one Title HIV T97A 31 35 IN;IN 42;64 51;73 28279801 Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness. Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness. 2017 Virus research Title HIV T369I;T369V 34;34 41;41 RT 79 100 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. 2017 Scientific reports Title HIV K65R 93 97 RT;RT 38;133 59;155 28366604 Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses. Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses. 2017 Vaccine Title HIV N277A 7 12 Env 65 73 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. 2017 mBio Title HIV R263K 4 9 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. 2017 The Journal of antimicrobial chemotherapy Title HIV K65R 23 27 NRTI 90 95 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. 2017 The Pediatric infectious disease journal Title HIV L74I;L74V 39;39 45;45 28396546 Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. 2017 Antimicrobial agents and chemotherapy Title HIV Q151M;Q151M 61;71 66;76 RT 29 50 28525359 I36T upward arrowT mutation in South African subtype C (C-SA) HIV-1 protease significantly alters protease-drug interactions. I36T T mutation in South African subtype C (C-SA) HIV-1 protease significantly alters protease-drug interactions. 2017 Biological chemistry Title HIV I36T 0 4 PR;PR 56;86 64;94 28533248 Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors. Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors. 2017 Antimicrobial agents and chemotherapy Title HIV L74F;V75I 26;35 30;39 IN;IN 16;107 25;116 28610923 L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase. L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase. 2017 Biochemical and biophysical research communications Title HIV L368F;M178I;V408F 0;71;7 5;76;12 IN 93 102 28645089 Drug Resistance Mechanism of L10F, L10F/N88S and L90M mutations in CRF01_AE HIV-1 protease: Molecular dynamics simulations and binding free energy calculations. Drug Resistance Mechanism of L10F, L10F/N88S and L90M mutations in CRF01_AE HIV-1 protease: Molecular dynamics simulations and binding free energy calculations. 2017 Journal of molecular graphics & modelling Title HIV L10F;L10F;L10F;L10F;L90M;N88S;N88S 29;35;29;35;49;40;40 33;39;33;39;53;44;44 PR 82 90 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. 2014 JMM case reports Title HIV Q3R;R77Q 9;0 12;4 Vpr 18 21 28832412 The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro. The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro. 2017 AIDS (London, England) Title HIV E157Q 20 25 IN 10 19 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. 2017 The Journal of antimicrobial chemotherapy Title HIV E138K;E138K;M184I;M184I;M184V;M184V;M184I;M184V 26;26;32;32;32;32;0;0 31;31;39;39;39;39;7;7 RT 68 89 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. 2018 AIDS research and human retroviruses Title HIV K65R 54 58 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. 2015 Biochemistry and biophysics reports Title HIV L33F 4 8 PR 104 112 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. 2018 Viruses Title HIV E157Q;R263K 56;46 61;51 IN 18 27 29373677 Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance. Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance. 2018 The Journal of antimicrobial chemotherapy Title HIV N155H 22 27 IN 46 55 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. 2018 Scientific reports Title HIV Q151M 26 31 RT;RT 48;121 50;123 29397520 An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L upward arrowN upward arrowL PR mutant. An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L N L PR mutant. 2018 Journal of computer-aided molecular design Title HIV L38L 82 86 PR;PR 65;91 67;93 29410019 Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. 2018 Antiviral research Title HIV C56S;G149A 26;35 30;40 IN 68 77 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. 2018 mBio Title HIV V32I 79 83 PR 100 108 29534929 First discovery of a potential carbonate prodrug of NNRTI drug candidate RDEA427 with submicromolar inhibitory activity against HIV-1 K103N/Y181C double mutant strain. First discovery of a potential carbonate prodrug of NNRTI drug candidate RDEA427 with submicromolar inhibitory activity against HIV-1 K103N/Y181C double mutant strain. 2018 Bioorganic & medicinal chemistry letters Title HIV K103N;Y181C 134;140 139;145 NNRTI 52 57 29550516 Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan. Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan. 2018 Antiviral research Title HIV A34R;K151E 107;85 111;90 Env 39 42 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. 2018 The Journal of infectious diseases Title HIV S230R 4 9 IN;IN 10;132 19;141 29633077 Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naive individuals. Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naive individuals. 2018 Archives of virology Title HIV K103N 70 75 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. 2018 European journal of medicinal chemistry Title HIV E138K 169 174 NNRTI 122 128 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. 2018 AIDS research and therapy Title HIV Q151M 34 39 29753024 Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase. Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase. 2018 Infection, genetics and evolution Title HIV Q151M 84 89 RT 106 127 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. 2018 Open forum infectious diseases Title HIV M184V 14 19 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. 2018 Viruses Title HIV A62V 32 36 RT 10 31 30047788 Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation. Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation. 2019 The Annals of pharmacotherapy Title HIV M184I;M184V 150;150 157;157 HIV infections 105 117 30103267 New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T). New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T). 2019 Chemical biology & drug design Title HIV M184L;M184T 117;127 123;132 NRTI;RT 28;94 60;115 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. 2018 ACS omega Title HIV L76V 25 29 PR 95 103 30462235 The HIV-1 reverse transcriptase E138A natural polymorphism decreases the genetic barrier to resistance to etravirine in vitro. The HIV-1 reverse transcriptase E138A natural polymorphism decreases the genetic barrier to resistance to etravirine in vitro. 2019 The Journal of antimicrobial chemotherapy Title HIV E138A 32 37 RT 10 31 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. 2018 Open forum infectious diseases Title HIV T97A 77 81 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. 2019 Open forum infectious diseases Title HIV R263K 19 24 30721060 Exploiting the Tolerant Region I of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Binding Pocket: Discovery of Potent Diarylpyrimidine-Typed HIV-1 NNRTIs against Wild-Type and E138K Mutant Virus with Significantly Improved Water Solubility and Favorable Safety Profiles. Exploiting the Tolerant Region I of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Binding Pocket: Discovery of Potent Diarylpyrimidine-Typed HIV-1 NNRTIs against Wild-Type and E138K Mutant Virus with Significantly Improved Water Solubility and Favorable Safety Profiles. 2019 Journal of medicinal chemistry Title HIV E138K 189 194 NNRTI;NNRTI;NNRTI 40;88;160 76;93;166 30738756 Mutational analysis of gyrB at amino acids: G481A & D505A in multidrug resistant (MDR) tuberculosis patients. Mutational analysis of gyrB at amino acids: G481A & D505A in multidrug resistant (MDR) tuberculosis patients. 2019 Journal of infection and public health Title HIV D505A;G481A 52;44 57;49 30814280 CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. 2019 Journal of virology Title HIV N57A 12 16 Capsid;Capsid 52;0 58;2 30839042 Targeting the hydrophobic channel of NNIBP: discovery of novel 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs with high potency against wild-type and K103N mutant virus. Targeting the hydrophobic channel of NNIBP: discovery of novel 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs with high potency against wild-type and K103N mutant virus. 2019 Organic & biomolecular chemistry Title HIV K103N 166 171 NNRTI 119 125 30944182 Effects of the SOS (A501C/T605C) and DS (I201C/A433C) Disulfide Bonds on HIV-1 Membrane Envelope Glycoprotein Conformation and Function. Effects of the SOS (A501C/T605C) and DS (I201C/A433C) Disulfide Bonds on HIV-1 Membrane Envelope Glycoprotein Conformation and Function. 2019 Journal of virology Title HIV A501C;I201C;A433C;T605C 20;41;47;26 25;46;52;31 Env 88 96 31090546 E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection. E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection. 2019 AIDS (London, England) Title HIV E157Q 0 5 IN 6 15 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. 2019 Biochemical and biophysical research communications Title HIV I47V;V32I;V82I 108;102;117 112;106;121 PR 53 61 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. 2019 Bioorganic & medicinal chemistry letters Title HIV Y181C 115 120 RT;NNRTI 134;86 155;91 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. 2019 Biochemistry Title HIV L89V;L90M 90;99 94;103 PR 45 53 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D G S mutant in the South African HIV-1 subtype C protease. 2019 Journal of enzyme inhibition and medicinal chemistry Title HIV E35D 78 82 PR;PR 50;131 58;139 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. 2019 The Journal of antimicrobial chemotherapy Title HIV M184I;M184V 160;160 167;167 31599568 Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. 2020 ACS infectious diseases Title HIV E138K;K103N 169;159 174;164 NNRTI 81 116 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. 2019 Open forum infectious diseases Title HIV M184I;M184V 14;14 21;21 31678241 Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses. Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses. 2020 Infection, genetics and evolution Title HIV E138G;V179E 51;20 56;25 RT 66 87 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. 2020 The Journal of infectious diseases Title HIV L74I;M184I;M184V 222;105;105 226;112;112 RT 74 95 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. 2019 Communications biology Title HIV M184V 102 114 RT 63 84 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. 2020 HIV medicine Title HIV M184I;M184V 110;110 117;117 31988104 Antiviral Activity of Tenofovir Alafenamide against HIV-1 with Thymidine Analog-Associated Mutations and M184V. Antiviral Activity of Tenofovir Alafenamide against HIV-1 with Thymidine Analog-Associated Mutations and M184V. 2020 Antimicrobial agents and chemotherapy Title HIV M184V 105 110 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. 2020 BMC infectious diseases Title HIV K65R;S68G 94;4 98;8 32057044 Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T/L89M by molecular dynamics simulations and free energy analyses. Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T/L89M by molecular dynamics simulations and free energy analyses. 2020 Physical chemistry chemical physics Title HIV G48T;L89M 158;163 162;167 PR 125 133 32065630 M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients. M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients. 2020 The Journal of antimicrobial chemotherapy Title HIV M184I;M184V 0;0 7;7 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. 2020 The Journal of antimicrobial chemotherapy Title HIV L74I 38 42 IN;IN 19;83 28;92 32141388 Presence of V72I, G123S and R127K Integrase Inhibitor polymorphisms could reduce ART effectiveness: a retrospective longitudinal study. Presence of V72I, G123S and R127K Integrase Inhibitor polymorphisms could reduce ART effectiveness: a retrospective longitudinal study. 2020 HIV research & clinical practice Title HIV G123S;R127K;V72I 18;28;12 23;33;16 IN 34 43 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. 2020 Viruses Title HIV N126K 69 74 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. 2020 BMC infectious diseases Title HIV K103R;V179D;V179D 34;40;24 39;45;29 NNRTI 86 121 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. 2020 The Journal of antimicrobial chemotherapy Title HIV M184I;M184V 26;26 33;33 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. 2020 Medicine Title HIV S230R 18 23 IN 24 33 32643196 Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site. Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site. 2020 Protein science Title HIV Y181C 79 84 RT;NNRTI 85;138 106;143 32737511 Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV. Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV. 2020 The Journal of antimicrobial chemotherapy Title HIV M184I;M184V 19;19 26;26 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. 2020 PloS one Title HIV H196Q 52 57 Nef 34 37 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. 2020 International journal of molecular sciences Title HIV Y44A 0 4 LTR;Tat;RT 88;44;62 91;47;83 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. 2020 SAGE open medicine Title HIV M184I;M184V 52;52 59;59 33076683 Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019. Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019. 2021 AIDS research and human retroviruses Title HIV M184V 123 128 33184634 Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir. Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir. 2021 The Journal of antimicrobial chemotherapy Title HIV R263K;S153F 39;28 44;33 IN 60 69 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. 2020 Viruses Title HIV M184I;M184V 163;163 170;170 IN 27 36 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. 2021 Journal of acquired immune deficiency syndromes (1999) Title HIV M184I;M184V 96;96 103;103 33352387 Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C. Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C. 2021 Bioorganic & medicinal chemistry Title HIV Y181C 137 142 RT 55 76 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). 2021 The Journal of antimicrobial chemotherapy Title HIV M184I;M184V 28;28 35;35 PR;PR 109;155 117;163 33722682 Dolutegravir response in antiretroviral therapy naive and experienced patients with M184V/I: Impact in low-and middle-income settings. Dolutegravir response in antiretroviral therapy naive and experienced patients with M184V/I: Impact in low-and middle-income settings. 2021 International journal of infectious diseases Title HIV M184I;M184V 84;84 91;91 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. 2021 The Journal of antimicrobial chemotherapy Title HIV K65R;M184V 24;14 28;19 HIV infections 59 71 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. 2021 Retrovirology Title HIV G10T 9 13 Gag;SP1 46;50 49;53 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. 2021 Viruses Title HIV M66I 100 104 Capsid 111 117 34090079 Exploiting the hydrophobic channel of the NNIBP: Discovery of novel diarylpyrimidines as HIV-1 NNRTIs against wild-type and K103N mutant viruses. Exploiting the hydrophobic channel of the NNIBP: Discovery of novel diarylpyrimidines as HIV-1 NNRTIs against wild-type and K103N mutant viruses. 2021 Bioorganic & medicinal chemistry Title HIV K103N 124 129 NNRTI 95 101 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. 2022 The Journal of infectious diseases Title HIV M184V 21 26 HIV infections 80 92 34419931 Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17. Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17. 2021 Journal of molecular graphics & modelling Title HIV V48G 19 23 PR;PR 84;93 92;95 34609269 Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. 2021 Journal of biomolecular structure & dynamics Title HIV D30N 69 73 PR 80 88 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. 2021 Viruses Title HIV M50I;V151I 17;26 21;31 IN 73 82 34919029 Revealing the drug resistance mechanism of saquinavir due to G48V and V82F mutations in subtype CRF01_AE HIV-1 protease: molecular dynamics simulation and binding free energy calculations. Revealing the drug resistance mechanism of saquinavir due to G48V and V82F mutations in subtype CRF01_AE HIV-1 protease: molecular dynamics simulation and binding free energy calculations. 2021 Journal of biomolecular structure & dynamics Title HIV G48V;V82F 61;70 65;74 PR 111 119 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. 2022 Molecules (Basel, Switzerland) Title HIV K103N;Y181C 59;65 64;70 RT 91 112 35061384 Development of Novel Dihydrofuro[3,4-d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C. Development of Novel Dihydrofuro[3,4-d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C. 2022 Journal of medicinal chemistry Title HIV F227L;K103N;V106A;Y181C 126;142;132;148 131;147;137;153 NNRTI 71 77 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. 2022 Clinical case reports Title HIV E138A 23 28 RT 46 67 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. 2022 Viruses Title HIV M46I 29 33 PR 82 90 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. 2022 AIDS (London, England) Title HIV M184I;M184V 124;124 132;132 35481647 Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer. Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer. 2022 Protein science Title HIV L289K 35 40 RT 47 68 7486942 K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. 1995 Antimicrobial agents and chemotherapy Title HIV K65R 0 4 RT 53 74 7517553 Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants. Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants. 1994 Proc Natl Acad Sci U S A Title HIV C181C;C181I;E138K;Y181C 199;206;143;198 207;211;148;203 RT;RT;RT;RT 48;71;149;212 69;73;151;214 7517668 Sensitivity of (138 Glu-->Lys) mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors. Sensitivity of (138 Glu-->Lys) mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors. 1994 Biochemical and biophysical research communications Title HIV E138K 16 29 RT;RT;RT 83;106;128 104;108;130 7522429 Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2',3'-didehydro-2',3'-dideoxythymidine in cell culture. Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2',3'-didehydro-2',3'-dideoxythymidine in cell culture. 1994 Antimicrobial agents and chemotherapy Title HIV V75T 16 20 RT 61 82 7523383 Resistance of HIV-1 reverse transcriptase against [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2''-dioxide)] (TSAO) derivatives is determined by the mutation Glu138-->Lys on the p51 subunit. Resistance of HIV-1 reverse transcriptase against [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2''-dioxide)] (TSAO) derivatives is determined by the mutation Glu138-->Lys on the p51 subunit. 1994 The Journal of biological chemistry Title HIV E138K 199 211 RT 20 41 7525567 The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. 1994 The Journal of biological chemistry Title HIV K65R 4 8 RT 16 37 7532595 Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 1995 FEBS letters Title HIV P236L 72 112 RT 160 181 7535930 Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. 1995 Proc Natl Acad Sci U S A Title HIV K65R 8 12 RT 25 46 7694651 Structure/function studies of HIV-1(1) reverse transcriptase: dimerization-defective mutant L289K. Structure/function studies of HIV-1(1) reverse transcriptase: dimerization-defective mutant L289K. 1993 Biochemistry Title HIV L289K 92 97 RT 39 60 7707502 Adaptation of human immunodeficiency virus type 1 to cells expressing a binding-deficient CD4 mutant (lysine 46 to aspartic acid). Adaptation of human immunodeficiency virus type 1 to cells expressing a binding-deficient CD4 mutant (lysine 46 to aspartic acid). 1995 Journal of virology Title HIV K46D 102 128 7773792 Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase. Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase. 1995 Nature structural biology Title HIV V82A 44 48 7918387 1H NMR structure and biological studies of the His23-->Cys mutant nucleocapsid protein of HIV-1 indicate that the conformation of the first zinc finger is critical for virus infectivity. 1H NMR structure and biological studies of the His23-->Cys mutant nucleocapsid protein of HIV-1 indicate that the conformation of the first zinc finger is critical for virus infectivity. 1994 Biochemistry Title HIV H23C 47 58 8356803 An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site. An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site. 1993 Virology Title HIV A582T 112 127 Env 108 111 8405409 Replacement of His23 by Cys in a zinc finger of HIV-1 NCp7 led to a change in 1H NMR-derived 3D structure and to a loss of biological activity. Replacement of His23 by Cys in a zinc finger of HIV-1 NCp7 led to a change in 1H NMR-derived 3D structure and to a loss of biological activity. 1993 FEBS letters Title HIV H23C 15 27 NC 54 56 8466899 Inhibitor binding to the Phe53Trp mutant of HIV-1 protease promotes conformational changes detectable by spectrofluorometry. Inhibitor binding to the Phe53Trp mutant of HIV-1 protease promotes conformational changes detectable by spectrofluorometry. 1993 Biochemistry Title HIV F53W 25 33 PR 50 58 8643604 Host-parasite dynamics and outgrowth of virus containing a single K70R amino acid change in reverse transcriptase are responsible for the loss of human immunodeficiency virus type 1 RNA load suppression by zidovudine. Host-parasite dynamics and outgrowth of virus containing a single K70R amino acid change in reverse transcriptase are responsible for the loss of human immunodeficiency virus type 1 RNA load suppression by zidovudine. 1996 Proc Natl Acad Sci U S A Title HIV K70R 66 70 RT 92 113 8676518 Increased polymerase fidelity of E89G, a nucleoside analog-resistant variant of human immunodeficiency virus type 1 reverse transcriptase. Increased polymerase fidelity of E89G, a nucleoside analog-resistant variant of human immunodeficiency virus type 1 reverse transcriptase. 1996 Journal of virology Title HIV E89G 33 37 RT;Pol 116;10 137;20 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. 1996 The Journal of biological chemistry Title HIV K65R 4 8 RT;Pol 73;40 94;50 8764080 Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1. Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1. 1996 Journal of virology Title HIV M184V 133 138 RT 11 32 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. 1996 Virology Title HIV K70R 21 29 RT;RT 33;150 54;152 8807067 The nucleoside analog-resistant E89G mutant of human immunodeficiency virus type 1 reverse transcriptase displays a broader cross-resistance that extends to nonnucleoside inhibitors. The nucleoside analog-resistant E89G mutant of human immunodeficiency virus type 1 reverse transcriptase displays a broader cross-resistance that extends to nonnucleoside inhibitors. 1996 Antimicrobial agents and chemotherapy Title HIV E89G 32 36 RT 83 104 8878611 Novel mutation (K70E) in human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to 9-[2-(phosphonomethoxy)ethyl]adenine in vitro. Novel mutation (K70E) in human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to 9-[2-(phosphonomethoxy)ethyl]adenine in vitro. 1996 Antimicrobial agents and chemotherapy Title HIV K70E 16 20 RT 61 82 8892925 An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3'-azido-3'-deoxythymidine. An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3'-azido-3'-deoxythymidine. 1996 Journal of virology Title HIV L210W 25 62 RT 102 123 8977101 The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant. The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant. 1996 FEBS letters Title HIV F185H 91 96 IN 53 62 9000632 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. 1996 Journal of molecular biology Title HIV Y181C 108 117 RT;RT 72;124 74;126 9030390 Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase. Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase. 1996 AIDS (London, England) Title HIV M184V 70 75 RT 112 133 9209307 Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. 1997 Leukemia Title HIV M184V 36 41 RT 56 77 9249032 The fidelity of 3' misinsertion and mispair extension during DNA synthesis exhibited by two drug-resistant mutants of the reverse transcriptase of human immunodeficiency virus type 1 with Leu74-->Val and Glu89-->Gly. The fidelity of 3' misinsertion and mispair extension during DNA synthesis exhibited by two drug-resistant mutants of the reverse transcriptase of human immunodeficiency virus type 1 with Leu74-->Val and Glu89-->Gly. 1997 European journal of biochemistry Title HIV E89G;L74V 204;188 215;199 RT 122 143 9343170 Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. 1997 Journal of virology Title HIV P225H 23 32 RT 89 110 9358162 Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. 1997 Nucleic acids research Title HIV M184V 58 63 RT 94 115 9450540 Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. 1997 FEBS letters Title HIV G48H 15 19 PR 36 44 9491916 A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. 1998 AIDS research and human retroviruses Title HIV F227L 18 23 NNRTI;RT 175;39 210;60 9514745 Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. 1998 Journal of molecular biology Title HIV M184V 83 88 RT 11 32 9521105 Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant. Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant. 1998 Protein science Title HIV A28S 111 115 PR 62 70 9557711 Increased misincorporation fidelity observed for nucleoside analog resistance mutations M184V and E89G in human immunodeficiency virus type 1 reverse transcriptase does not correlate with the overall error rate measured in vitro. Increased misincorporation fidelity observed for nucleoside analog resistance mutations M184V and E89G in human immunodeficiency virus type 1 reverse transcriptase does not correlate with the overall error rate measured in vitro. 1998 Journal of virology Title HIV E89G;M184V 98;88 102;93 RT 142 163 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. 1998 Nucleic acids research Title HIV M184I 41 46 RT 124 145 9619801 The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors. The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors. 1998 AIDS (London, England) Title HIV M184V 4 9 RT;RT;RT 28;51;153 49;53;155 9634074 A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152. A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152. 1998 The Journal of general virology Title HIV P225H 2 51 RT;RT;RT 99;122;143 120;124;145 9643373 Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. 1998 AIDS research and human retroviruses Title HIV M184V 137 142 RT 114 135 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. 1998 Molecular pharmacology Title HIV K70E 73 77 RT 36 57 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. 1998 The Journal of biological chemistry Title HIV E89G 17 21 RT;Pol 44;89 65;99 9742239 The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency. The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency. 1998 Nucleic acids research Title HIV E89G;M184V 42;51 46;56 RT 93 114 9813120 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. 1998 Journal of molecular biology Title HIV Y188L 14 23 RT 51 72 9841827 Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro. Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro. 1999 The Journal of infectious diseases Title HIV M184V 73 78 RT 91 112 9865962 Solution structure of the His12 --> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium. Solution structure of the His12 --> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium. 1998 Protein science Title HIV H12C 26 39 IN 94 103 10074125 A second-site mutation that restores replication of a Tat-defective human immunodeficiency virus. The inactive Y26A mutant yielded the second-site suppressor mutation Y47N that partially restored trans-activation activity and virus replication. 1999 Journal of virology Abstract HIV Y26A;Y47N 13;69 17;73 10074125 A second-site mutation that restores replication of a Tat-defective human immunodeficiency virus. We conclude that the gain of function measured for the Y47N change is not specific for the Y26A mutant, arguing against a direct interaction of Tat amino acids 26 and 47 in the three-dimensional fold of this protein. 1999 Journal of virology Abstract HIV Y26A;Y47N 91;55 95;59 Tat 144 147 10074177 Mutational analysis of Vpr-induced G2 arrest, nuclear localization, and cell death in fission yeast. Furthermore, two single point mutations (H33R and H71R), both of which reside at the end of each alpha-helix, disrupted all three Vpr functions, indicating that these two mutations may have strong effects on the overall Vpr structure. 1999 Journal of virology Abstract HIV H33R;H71R 41;50 46;54 Vpr;Vpr 130;220 133;223 10082371 Molecular mechanisms of resistance: free energy calculations of mutation effects on inhibitor binding to HIV-1 protease. The changes in the inhibitor binding constants due to the mutation of isoleucine to valine at position 84 of HIV-1 protease are calculated using molecular dynamics simulations. 1998 Protein science Abstract HIV I84V 70 105 PR 115 123 10103184 9-[2-(Phosphonomethoxy)propyl]adenine (PMPA) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to PMPA. In conclusion, this study demonstrates that although SIVmac mutants with the PMPA-selected K65R mutation in RT were highly virulent, PMPA treatment still offered strong therapeutic benefits. 1999 Antimicrobial agents and chemotherapy Abstract HIV K65R 91 95 RT 108 110 10103184 9-[2-(Phosphonomethoxy)propyl]adenine (PMPA) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to PMPA. In several other animals, additional RT mutations, including K64R and Y115F, were detected, but the biological role of these mutations is unclear since they did not affect the in vitro susceptibility of the virus to PMPA. 1999 Antimicrobial agents and chemotherapy Abstract HIV K64R;Y115F 61;70 65;75 RT 37 39 10103184 9-[2-(Phosphonomethoxy)propyl]adenine (PMPA) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to PMPA. To study directly the virulence and clinical implications of these SIV mutants, two uncloned SIVmac isolates with similar fivefold reduced in vitro susceptibilities to PMPA but distinct RT genotypes, SIVmac055 (K65R, N69T, R82K A158S,S211N) and SIVmac385 (K65R, N69S, I118V), were each inoculated intravenously into six newborn rhesus macaques; 3 weeks later, three animals of each group were started on PMPA treatment. 1999 Antimicrobial agents and chemotherapy Abstract HIV A158S;I118V;K65R;K65R;N69S;N69T;R82K;S211N 228;268;211;256;262;217;223;234 233;273;215;260;266;221;227;239 RT 186 188 10103184 9-[2-(Phosphonomethoxy)propyl]adenine (PMPA) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to PMPA. Virus from only one untreated animal demonstrated reversion to wild-type susceptibility and loss of the K65R mutation. 1999 Antimicrobial agents and chemotherapy Abstract HIV K65R 104 108 10103184 9-[2-(Phosphonomethoxy)propyl]adenine (PMPA) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to PMPA. We previously demonstrated that SIV-infected infant macaques receiving prolonged treatment with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) developed viral mutants with fivefold reduced susceptibility to PMPA in vitro and that the development of these mutants was associated with the development of a K65R mutation and additional compensatory mutations in reverse transcriptase (RT). 1999 Antimicrobial agents and chemotherapy Abstract HIV K65R 302 306 RT;RT 357;380 378;382 10195266 Fast genotypic detection of drug resistance mutations in the HIV-1 reverse transcriptase gene of treatment-naive patients. Additionally, a selective polymerase chain reaction (PCR) for the multiple dideoxynucleoside resistance (MddNR) mutation Q151M was performed. 1998 Journal of human virology Abstract HIV Q151M 121 126 Pol 26 36 10195266 Fast genotypic detection of drug resistance mutations in the HIV-1 reverse transcriptase gene of treatment-naive patients. Mutation K70R (resistance to zidovudine) was found in 8 patients, M41L (resistance to zidovudine) in 5 patients, M184V/I (resistance to ddI/ddC/3TC) in 2 patients, and T215Y/F (resistance to zidovudine) in 4 patients. 1998 Journal of human virology Abstract HIV K70R;M184I;M184V;M41L;T215F;T215Y 9;113;113;66;168;168 13;120;120;70;175;175 10196268 Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. A major natural polymorphism of the HIV-1 protease, L63P, compensated well for the impairment of fitness caused by L90M but only slightly improved the fitness of D30N. 1999 Journal of virology Abstract HIV D30N;L63P;L90M 162;52;115 166;56;119 PR 42 50 10196268 Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. A nelfinavir-selected protease D30N substitution substantially decreased replicative capacity relative to WT, while a saquinavir-selected L90M substitution moderately decreased fitness. 1999 Journal of virology Abstract HIV D30N;L90M 31;138 35;142 PR 22 30 10196268 Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. Hypotheses based on the greater fitness impairment of the nelfinavir-selected D30N mutant are suggested to explain observations that prolonged responses to delayed salvage regimens, including alternate PIs, may be relatively common after nelfinavir failure. 1999 Journal of virology Abstract HIV D30N 78 82 PI 202 205 10196268 Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. Multiply substituted indinavir-selected mutants M46I/L63P/V82T/I84V and L10R/M46I/L63P/V82T/I84V were just as fit as WT. 1999 Journal of virology Abstract HIV I84V;I84V;L10R;L63P;L63P;M46I;M46I;V82T;V82T 63;92;72;53;82;77;48;58;87 67;96;76;57;86;81;52;62;91 10196268 Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. The D30N mutant virus was also outcompeted by the L90M mutant in the absence of drugs. 1999 Journal of virology Abstract HIV D30N;L90M 4;50 8;54 10196268 Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. These results indicate that the mutations which are usually initially selected by nelfinavir and saquinavir, D30N and L90M, respectively, impair fitness. 1999 Journal of virology Abstract HIV D30N;L90M 109;118 113;122 10199226 Clinical cross-resistance between the HIV-1 protease inhibitors saquinavir and indinavir and correlations with genotypic mutations. Six of the patients had developed five or more mutations: L90M in two, G48V in four (of which three also contained L101), and V82A in three. 1999 AIDS (London, England) Abstract HIV G48V;L90M;V82A 71;58;126 75;62;130 10202820 Virologic responses to a ritonavir--saquinavir-containing regimen in patients who had previously failed nelfinavir. The most frequent baseline mutations in the protease gene prior to switching were D30N (13 out of 18), N88D (eight out of 18) and M36I (eight out of 18). 1999 AIDS (London, England) Abstract HIV D30N;M36I;N88D 82;130;103 86;134;107 PR 44 52 10207547 Insertion of two amino acids combined with changes in reverse transcriptase containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs. RESULTS: Among viruses from 92 patients studied, three (3%) viruses contained a T215Y amino-acid change as well as a previously unseen combination of an amino-acid change at codon 67 (N-->E/S) and a two amino-acid insertion between codons 68 and 69 of the RT gene of HIV-1. 1999 AIDS (London, England) Abstract HIV T215Y 80 85 RT 256 258 10208938 In vitro assembly properties of wild-type and cyclophilin-binding defective human immunodeficiency virus capsid proteins in the presence and absence of cyclophilin A. Variant CA proteins G89L and G89F yielded similar cylinders as the WT protein but were significantly more resistant to CypA. 1999 Virology Abstract HIV G89F;G89L 29;20 33;24 Capsid 8 10 10208939 Cyclophilin A incorporation is not required for human immunodeficiency virus type 1 particle maturation and does not destabilize the mature capsid. Virus produced from cyclosporin-treated cells and variants G89V and G89A were 10- to 100-fold less infectious but exhibited normal virion morphologies with regular cone-shaped capsids. 1999 Virology Abstract HIV G89A;G89V 68;59 72;63 Capsid 176 183 10228055 Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor-experienced persons. Rapid failure was surprisingly associated with baseline presence of protease gene mutation L90M (P=.04) in the absence of D30N and with RT mutations D67N (P<.01), K70R/S (P=.02), and K219Q/W/R/E (P<.01). 1999 The Journal of infectious diseases Abstract HIV D30N;D67N;K219E;K219Q;K219R;K219W;K70R;K70S;L90M 122;149;183;183;183;183;163;163;91 126;153;194;194;194;194;169;169;95 PR;RT 68;136 76;138 10353158 Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase. 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (wild and Y181C mutant types). 1999 Phytotherapy research Abstract HIV Y181C 194 199 RT;Pol;RT 157;59;180 178;69;182 10353158 Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase. These extracts were refractioned into four fractions; 2I4 and 4I4 were active as inhibitors of DNA-polymerase (wild and Y181C types) and RNase H activities. 1999 Phytotherapy research Abstract HIV Y181C 120 125 Pol 99 109 10364282 Comparative fitness of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 (HIV-1) in an In vitro competitive HIV-1 replication assay. We examined whether human immunodeficiency virus type 1 (HIV-1) fitness was altered upon the acquisition of a set or subset of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene, which confers resistance to multiple dideoxynucleosides (MDR), as well as the zidovudine resistance-associated mutation T215Y, using a competitive HIV-1 replication assay in a setting of an HXB2D genetic background. 1999 Journal of virology Abstract HIV A62V;F116Y;F77L;Q151M;T215Y;V75I 143;161;155;172;316;149 147;166;159;177;321;153 Pol 186 189 10364329 Analysis of the effect of natural sequence variation in Tat and in cyclin T on the formation and RNA binding properties of Tat-cyclin T complexes. Surprisingly, mutation of a single residue in CycT2 (asparagine 260 to cysteine) rescues the ability of CycT2 to bind Tat1 and also activates not only TAR binding by all three Tat-CycT2 complexes but also Tat function. 1999 Journal of virology Abstract HIV N260C 53 79 Tat;Tat;Tat 118;176;205 121;179;208 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. At high concentrations of DLV, P236L replication and K103N replication were both inhibited. 1999 Journal of virology Abstract HIV K103N;P236L 53;31 58;36 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. At low levels of DLV, growth of wild-type virus was severely inhibited, and K103N replicated two- to threefold more efficiently than P236L. 1999 Journal of virology Abstract HIV K103N;P236L 76;133 81;138 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. In the absence of DLV, p24 production by wild-type virus occurred more rapidly and to higher levels than with either mutant; P236L consistently demonstrated a two- to threefold decrease in p24 relative to K103N. 1999 Journal of virology Abstract HIV K103N;P236L 205;125 210;130 p24;p24 23;189 26;192 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. K103N demonstrated normal RNA 5'-end-directed RNase H cleavage and slowed DNA 3'-end-directed RNase H cleavage compared to wild-type RT. 1999 Journal of virology Abstract HIV K103N 0 5 RT 133 135 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. P236L demonstrated slowing of both DNA 3'-end- and RNA 5'-end-directed RNase H cleavage, consistent with its reduced replication efficiency relative to K103N. 1999 Journal of virology Abstract HIV K103N;P236L 152;0 157;5 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. Recombinant RTs containing K103N or P236L were analyzed for DNA polymerization on heteropolymeric RNA templates and RNase H degradation of RNA-DNA hybrids. 1999 Journal of virology Abstract HIV K103N;P236L 27;36 32;41 RT 12 15 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. The nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) delavirdine (DLV) selects in vitro for the human immunodeficiency virus type 1 (HIV-1) RT mutation P236L, which confers high-level resistance to DLV but not other NNRTIs. 1999 Journal of virology Abstract HIV P236L 162 167 NNRTI;NNRTI;NNRTI;RT;RT 4;56;226;41;150 39;61;232;43;152 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. Unexpectedly, P236L has developed infrequently in HIV-1 isolates obtained from patients receiving DLV; K103N is the predominant resistance mutation observed in that setting. 1999 Journal of virology Abstract HIV K103N;P236L 103;14 108;19 10364332 The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. We characterized the replication fitness of viruses derived from pNL4-3 containing P236L or K103N in both H9 and primary human peripheral blood mononuclear cell cultures infected in parallel with the two mutants. 1999 Journal of virology Abstract HIV K103N;P236L 92;83 97;88 10386942 Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus. RT assays revealed that HI-236 was not only more potent than trovirdine, MKC-442, and AZT against the drug-sensitive HIV-1 strain HTLV(IIIB), it was also 50-100 times more effective than delavirdine or nevirapine and twice as effective as our recently reported lead compound N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240) against the NNI-resistant Y181C mutant HIV-1 strain A17. 1999 Bioorganic & medicinal chemistry letters Abstract HIV Y181C 369 374 RT 0 2 10388652 Isolation and characterization of an oligomerization-negative mutant of HIV-1 integrase. Mutant virus carrying the V260E substitution was blocked in replication at the time of DNA integration, consistent with IN multimerization being important for its activity in vivo. 1999 Virology Abstract HIV V260E 26 31 IN 120 122 10388652 Isolation and characterization of an oligomerization-negative mutant of HIV-1 integrase. The responsible mutation, leading to a single amino acid change (V260E) in the C-terminal domain of IN, blocks IN-IN multimerization but has only small effect on binding to a host interacting protein, INI1 (hSNF5). 1999 Virology Abstract HIV V260E 65 70 IN;IN;IN;IN 201;100;111;114 204;102;113;116 10388843 Molecular mechanics analysis of drug-resistant mutants of HIV protease. In order to study drug resistance, the wild-type HIV-1 protease and the mutants R8Q, V32I, M46I, V82A, V82I, V82F, I84V, V32I/I84V and M46I/I84V were modeled with the inhibitors saquinavir and indinavir using the program AMMP. 1999 Protein engineering Abstract HIV I84V;I84V;I84V;M46I;M46I;R8Q;V32I;V32I;V82A;V82F;V82I 126;140;115;91;135;80;85;121;97;109;103 130;144;119;95;139;83;89;125;101;113;107 PR 55 63 10388843 Molecular mechanics analysis of drug-resistant mutants of HIV protease. The exception was R8Q with indinavir, probably due to differences in the solvation energy. 1999 Protein engineering Abstract HIV R8Q 18 21 10390221 Sequence diversity of the reverse transcriptase of human immunodeficiency virus type 1 from untreated Brazilian individuals. One sample (brp004, subtype B) showed an AZT resistance secondary mutation at position K70R. 1999 Antimicrobial agents and chemotherapy Abstract HIV K70R 87 91 10390221 Sequence diversity of the reverse transcriptase of human immunodeficiency virus type 1 from untreated Brazilian individuals. The isolate brp004 also carried a D67N AZT resistance mutation revealed by direct sequencing. 1999 Antimicrobial agents and chemotherapy Abstract HIV D67N 34 38 10390221 Sequence diversity of the reverse transcriptase of human immunodeficiency virus type 1 from untreated Brazilian individuals. Three of these non-B isolates, named brp004, brp063, and brp069, revealed three other relevant AZT resistance mutations-a T215F mutation and two M41L mutations, respectively-hidden by the nonreactivity to line probe assay strips on the respective codon regions. 1999 Antimicrobial agents and chemotherapy Abstract HIV M41L;T215F 145;122 149;127 10395818 Mutational analysis of Phe160 within the "palm" subdomain of human immunodeficiency virus type 1 reverse transcriptase. F160Y and F160W retained substantial DNA polymerase activity, whereas the catalytic efficiency of nucleotide incorporation of mutants F160I, F160A and F160Q was less than 10 % that of the wild-type RT, using poly(rA).oligo(dT)20 as the template-primer. 1999 Journal of molecular biology Abstract HIV F160A;F160I;F160Q;F160W;F160Y 141;134;151;10;0 146;139;156;15;5 Pol;RT 41;198 51;200 10395818 Mutational analysis of Phe160 within the "palm" subdomain of human immunodeficiency virus type 1 reverse transcriptase. F160Y displayed similar kinetic parameters as the wild-type RT in nucleotide insertion assays carried out with heteropolymeric DNA/DNA template-primers. 1999 Journal of molecular biology Abstract HIV F160Y 0 5 RT 60 62 10395818 Mutational analysis of Phe160 within the "palm" subdomain of human immunodeficiency virus type 1 reverse transcriptase. Fidelity assays revealed similar misinsertion and mispair extension ratios for the three enzymes, although F160W showed a slightly higher accuracy of DNA synthesis, particularly in the presence of high concentrations of dNTP. 1999 Journal of molecular biology Abstract HIV F160W 107 112 10395818 Mutational analysis of Phe160 within the "palm" subdomain of human immunodeficiency virus type 1 reverse transcriptase. Five mutant RTs having Tyr, Trp, Ile, Ala or Gln instead of Phe160 were obtained by site-directed mutagenesis. 1999 Journal of molecular biology Abstract HIV F160A;F160W;F160I;F160Q 28;28;28;28 66;66;66;66 RT 12 15 10395818 Mutational analysis of Phe160 within the "palm" subdomain of human immunodeficiency virus type 1 reverse transcriptase. However, nucleotide affinity was two- to sixfold reduced in the case of mutant F160W. 1999 Journal of molecular biology Abstract HIV F160W 79 84 10395818 Mutational analysis of Phe160 within the "palm" subdomain of human immunodeficiency virus type 1 reverse transcriptase. The low catalytic efficiency of mutants F160I, F160A and F160Q was due to their lower affinity for the dNTP substrate. 1999 Journal of molecular biology Abstract HIV F160A;F160I;F160Q 47;40;57 52;45;62 10395818 Mutational analysis of Phe160 within the "palm" subdomain of human immunodeficiency virus type 1 reverse transcriptase. When introduced in an infectious proviral clone, mutations F160I, F160A and F160Q rendered non-viable virus. 1999 Journal of molecular biology Abstract HIV F160A;F160I;F160Q 66;59;76 71;64;81 10397560 Highly drug-resistant HIV-1 clinical isolates are cross-resistant to many antiretroviral compounds in current clinical development. The isolates included one multinucleoside-resistant virus containing the Q151M mutation, and four clinical isolates containing multiple RT and protease resistance mutations. 1999 AIDS (London, England) Abstract HIV Q151M 73 78 PR;RT 143;136 151;138 10400720 Second-site reversion of a human immunodeficiency virus type 1 reverse transcriptase mutant that restores enzyme function and replication capacity. However, in all cases an additional substitution in the primer grip of the RT (M230I) emerged when the virus increased its replication capacity. 1999 Journal of virology Abstract HIV M230I 79 84 RT 75 77 10400720 Second-site reversion of a human immunodeficiency virus type 1 reverse transcriptase mutant that restores enzyme function and replication capacity. Nucleotide sequence analysis of the progeny virus recovered from supernatants of four independent transfection experiments showed that the Y115W mutation was maintained. 1999 Journal of virology Abstract HIV Y115W 139 144 10400720 Second-site reversion of a human immunodeficiency virus type 1 reverse transcriptase mutant that restores enzyme function and replication capacity. Several mutations at this position (Y115W, Y115L, Y115A, and Y115D) were introduced in an infectious HIV-1 clone, and the replicative capacity of the mutant viruses was monitored. 1999 Journal of virology Abstract HIV Y115A;Y115D;Y115L;Y115W 50;61;43;36 55;66;48;41 10400720 Second-site reversion of a human immunodeficiency virus type 1 reverse transcriptase mutant that restores enzyme function and replication capacity. Using recombinant HIV-1 RT, we demonstrate that M230I mitigates the polymerase activity defect of the Y115W mutant, by increasing the dNTP binding affinity of the enzyme. 1999 Journal of virology Abstract HIV M230I;Y115W 48;102 53;107 Pol;RT 68;24 78;26 10400720 Second-site reversion of a human immunodeficiency virus type 1 reverse transcriptase mutant that restores enzyme function and replication capacity. Y115W was the only mutant able to replicate in MT-4 cells, albeit very poorly. 1999 Journal of virology Abstract HIV Y115W 0 5 10400754 RNase H requirements for the second strand transfer reaction of human immunodeficiency virus type 1 reverse transcription. However, in the presence of Mg2+, the E478Q RT mutant had no detectable RNase H activity and was unable to support strand transfer. 1999 Journal of virology Abstract HIV E478Q 38 43 RT 44 46 10400754 RNase H requirements for the second strand transfer reaction of human immunodeficiency virus type 1 reverse transcription. In reactions in which the E478Q RT was complemented with exogenous RNase H enzymes, strand transfer was supported. 1999 Journal of virology Abstract HIV E478Q 26 31 RT 32 34 10400754 RNase H requirements for the second strand transfer reaction of human immunodeficiency virus type 1 reverse transcription. In the presence of Mn2+, the E478Q RT yields the initial endoribonucleolytic cleavage at the penultimate C residue of the tRNA primer yet does not support strand transfer. 1999 Journal of virology Abstract HIV E478Q 29 34 RT 35 37 10400754 RNase H requirements for the second strand transfer reaction of human immunodeficiency virus type 1 reverse transcription. Utilizing wild-type HIV-1 RT and a mutant E478Q RT, the requirement for RNase H activity in this strand transfer event was analyzed. 1999 Journal of virology Abstract HIV E478Q 42 47 RT;RT 26;48 28;50 10400757 Mutagenesis of CXCR4 identifies important domains for human immunodeficiency virus type 1 X4 isolate envelope-mediated membrane fusion and virus entry and reveals cryptic coreceptor activity for R5 isolates. Using a panel of 41 different CXCR4 mutants, we have identified several charged residues that appear important for coreceptor activity for X4 Envs; the mutations E15A (in which the glutamic acid residue at position 15 is replaced by alanine) and E32A in the N terminus, D97A in extracellular loop 1 (ecl-1), and R188A in ecl-2 impaired coreceptor activity for X4 and R5X4 Envs. 1999 Journal of virology Abstract HIV D97A;E15A;E15A;E32A;R188A 270;162;181;246;312 274;166;240;250;317 Env;Env 142;372 146;376 10400757 Mutagenesis of CXCR4 identifies important domains for human immunodeficiency virus type 1 X4 isolate envelope-mediated membrane fusion and virus entry and reveals cryptic coreceptor activity for R5 isolates. We have also identified substitutions which greatly enhance or convert CXCR4's coreceptor activity to support R5 Env-mediated fusion (N11A, R30A, D187A, and D193A), and together our data suggest the presence of conserved extracellular elements, common to both CXCR4 and CCR5, involved in their coreceptor activities. 1999 Journal of virology Abstract HIV D187A;D193A;N11A;R30A 146;157;134;140 151;162;138;144 Env 113 116 10400801 Mutations within four distinct gag proteins are required to restore replication of human immunodeficiency virus type 1 after deletion mutagenesis within the dimerization initiation site. In the case of BH10-LD3, these four mutations were MA1, CA1, MP2, and MNC, and they involved changes of amino acid Val-35 to Ile within the matrix protein (MA), Ile-91 to Thr within the capsid (CA), Thr-12 to Ile within p2, and Thr-24 to Ile within the nucleocapsid (NC). 1999 Journal of virology Abstract HIV I91T;T12I;T24I;V35I 161;199;228;115 174;212;241;128 Capsid;Matrix;NC;Matrix;Matrix;Capsid;Capsid 186;140;267;51;156;56;194 192;146;269;53;158;58;196 10400801 Mutations within four distinct gag proteins are required to restore replication of human immunodeficiency virus type 1 after deletion mutagenesis within the dimerization initiation site. The first two of these were identical to those described above, while the last involved a change of Val-35 to Leu. 1999 Journal of virology Abstract HIV V35L 100 113 10413462 The mobility of an HIV-1 integrase active site loop is correlated with catalytic activity. X-ray structures of the catalytic domain mutants G149A and G140A/G149A show further rigidity of alpha4 and the adjoining loop. 1999 Biochemistry Abstract HIV G140A;G149A;G149A 59;49;65 64;54;70 10413520 Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. A dramatic 146- and 117-fold decrease in incorporation efficiency was observed for 3TC-MP incorporation by M184V RT for DNA- and RNA-dependent DNA polymerization, respectively, as compared with wild-type HIV-1 RT. 1999 Biochemistry Abstract HIV M184V 107 112 RT;RT 113;210 115;212 10413520 Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. A single amino acid substitution from methionine-184 to valine (M184V) of HIV-1 reverse transcriptase (RT) evokes the 1000-fold 3TC (Lamivudine) resistance by the HIV-1 virus observed in the clinic. 1999 Biochemistry Abstract HIV M184V;M184V 64;38 69;62 RT;RT 80;103 101;105 10413520 Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. The fidelity of M184V RT was also examined to evaluate mispair formation since this mutant has been suggested to exhibit a higher level of fidelity. 1999 Biochemistry Abstract HIV M184V 16 21 RT 22 24 10413520 Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. The M184V mutant HIV-1 RT was studied to assess its catalytic efficiency during single nucleotide incorporation using a transient kinetic approach. 1999 Biochemistry Abstract HIV M184V 4 9 RT 23 25 10413520 Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. The results of our studies indicate that there is a maximum 2.4-fold increase in fidelity for M184V RT as compared with wild-type HIV-1 RT. 1999 Biochemistry Abstract HIV M184V 94 99 RT;RT 100;136 102;138 10413520 Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. This mechanistic information provides insight into our understanding of the molecular mechanism of 3TC-drug resistance and supports suggestions that increased RT fidelity and decreased fitness of the M184V HIV-1 virus may be factors contributing to the strong antiviral effect of AZT-3TC combination therapy. 1999 Biochemistry Abstract HIV M184V 200 205 RT 159 161 10413520 Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. While the k(pol) was slower and the K(d) was weaker for 3TC-TP incorporation by the M184V RT, the decrease in the efficiency of incorporation is primarily due to a substantially reduced binding affinity for the 3TC-TP to the enzyme.DNA (or RNA) complex poised for DNA elongation. 1999 Biochemistry Abstract HIV M184V 84 89 Pol;RT 12;90 15;92 10416525 Long-term evaluation of triple nucleoside therapy administered from primary HIV-1 infection. M184V and/or T215Y mutations were demonstrated in two of these last five patients. 1999 AIDS (London, England) Abstract HIV T215Y;M184V 13;0 18;5 10421048 Multiple drug resistance genotype causing failure of antiretroviral treatment in an HIV-infected patient heavily exposed to nucleoside analogues. A point mutation nested PCR assay showed that the patient carried a virus with a codon Q151M mutation, which confers multiple drug resistance to nucleoside analogues. 1999 European journal of clinical microbiology & infectious diseases Abstract HIV Q151M 87 92 10421048 Multiple drug resistance genotype causing failure of antiretroviral treatment in an HIV-infected patient heavily exposed to nucleoside analogues. Genetic sequence analysis showed that, despite none of the classically associated mutations to Q151M being present at the beginning of treatment, continuous genetic evolution under selective drug pressure allowed the virus to accumulate mutations at codons 62, 74 and 116 over time. 1999 European journal of clinical microbiology & infectious diseases Abstract HIV Q151M 95 100 10421243 Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. Among ZDV-resistant study subjects at week 24 (n = 17), those with mutant RT M184V codon had a more favorable HIV-1 RNA slope than those with wild-type RT 184M codon (p = .0551). 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 77 82 RT;RT 74;152 76;154 10421243 Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. Emergence of the M184V RT mutation at week 48 was detected in 3 of 16 (18.7%) initially drug-naive subjects as opposed to 21 of 40 (52.5%) ZDV-pretreated patients. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 17 22 RT 23 25 10421243 Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. Multivariate logistic analysis detected HIV-1 RNA load at week 24 as the best predictor of subsequent selection of the M184V mutant (p = .0121). 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 119 124 10421243 Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. These findings suggest that development of the 3TC-resistance M184V mutation under triple therapy with 3TC, ZDV, and a PI may have unexpected beneficial effects in vivo in addition to those associated with resensitization of ZDV-resistant virus to ZDV. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 62 67 PI 119 121 10421243 Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. To analyze the emergence and role of the lamivudine (3TC)-selected HIV-1 reverse transcriptase (RT) M184V mutation under triple therapy, we performed a retrospective study of 40 nucleoside RT inhibitor-pretreated and 16 drug-naive patients who were switched to combined treatment with zidovudine (ZDV) plus 3TC plus a protease inhibitor (PI). 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 100 105 RT;PR;PI;RT;RT 73;318;338;96;189 94;326;340;98;191 10428105 Presence of mutation conferring resistance to lamivudine in plasma and cerebrospinal fluid of HIV-1-infected patients. In 4, the lamivudine (3TC)-resistance mutation M184V was found in both CSF and plasma. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 47 52 10428105 Presence of mutation conferring resistance to lamivudine in plasma and cerebrospinal fluid of HIV-1-infected patients. In both, M184V was found in plasma but not CSF. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 9 14 10428899 Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide. Further enhancement of activity is observed with RTs that possess the Y181C change together with mutations that yield resistance to AZT. 1999 Antimicrobial agents and chemotherapy Abstract HIV Y181C 70 75 RT 49 52 10428899 Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide. Selection of viruses resistant to each of the three compounds in a variety of cell lines yielded viruses with T139I, L100I, Y188H, or L187F amino acid changes in the RT. 1999 Antimicrobial agents and chemotherapy Abstract HIV L100I;L187F;T139I;Y188H 117;134;110;124 122;139;115;129 RT 166 168 10428899 Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide. The calanolide analogs, however, exhibit 10-fold enhanced antiviral activity against drug-resistant viruses that bear the most prevalent NNRTI resistance that is engendered by amino acid change Y181C in the RT. 1999 Antimicrobial agents and chemotherapy Abstract HIV Y181C 194 199 NNRTI;RT 137;207 142;209 10428920 A family of insertion mutations between codons 67 and 70 of human immunodeficiency virus type 1 reverse transcriptase confer multinucleoside analog resistance. Modelling the 69Ser-(Ser-Ser) insertion into the RT structure demonstrated the profound direct effect that this change is likely to have in the nucleoside triphosphate binding site of the enzyme. 1999 Antimicrobial agents and chemotherapy Abstract HIV Ins 69S 14 29 RT 49 51 10428920 A family of insertion mutations between codons 67 and 70 of human immunodeficiency virus type 1 reverse transcriptase confer multinucleoside analog resistance. Site-directed mutagenesis studies confirmed that 69Ser-(Ser-Ser) in an AZT resistance mutational background conferred simultaneous resistance to multiple nucleoside analogs. 1999 Antimicrobial agents and chemotherapy Abstract HIV Ins 69S 49 64 10428920 A family of insertion mutations between codons 67 and 70 of human immunodeficiency virus type 1 reverse transcriptase confer multinucleoside analog resistance. These insertions were found between RT codons 67 and 70 and were commonly 69Ser-(Ser-Ser) or 69Ser-(Ser-Gly). 1999 Antimicrobial agents and chemotherapy Abstract HIV Ins 69S;Ins 69S 74;93 89;108 RT 36 38 10428942 A new point mutation (P157S) in the reverse transcriptase of human immunodeficiency virus type 1 confers low-level resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine. A P157S mutation in the reverse transcriptase (RT) of human immunodeficiency virus type 1 conferred fivefold resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine in cell culture. 1999 Antimicrobial agents and chemotherapy Abstract HIV P157S 2 7 RT;RT 24;47 45;49 10428942 A new point mutation (P157S) in the reverse transcriptase of human immunodeficiency virus type 1 confers low-level resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine. A similar increase in susceptibility to AZT and to PMPA was also conferred by the M184V mutation in RT. 1999 Antimicrobial agents and chemotherapy Abstract HIV M184V 82 87 RT 100 102 10428942 A new point mutation (P157S) in the reverse transcriptase of human immunodeficiency virus type 1 confers low-level resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine. Interestingly, the P157S mutation resulted in increased sensitivity (two- to threefold) to 3'-azido-3'-deoxythymidine (AZT) and to (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). 1999 Antimicrobial agents and chemotherapy Abstract HIV P157S 19 24 10429209 Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. In contrast, D30N is variable in its activity on different substrates (10-110% of wild-type), with the PR-RT site being the most affected. 1999 European journal of biochemistry Abstract HIV D30N 13 17 PR;RT 103;106 105;108 10429209 Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. Mutant V82S is the least active (2-20% of wild-type protease), mutants N88D, R8Q, and L90M exhibit activities ranging from 20 to 40% and G48V from 50 to 80% of the wild-type activity. 1999 European journal of biochemistry Abstract HIV G48V;L90M;N88D;R8Q;V82S 137;86;71;77;7 141;90;75;80;11 PR 52 60 10429209 Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. Mutants K45I and M46L, usually selected in combination with other mutations, showed activities that are similar to (60-110%) or greater than (110-530%) wild-type, respectively. 1999 European journal of biochemistry Abstract HIV K45I;M46L 8;17 12;21 10429209 Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. Mutants of HIV-1 protease that are commonly selected on exposure to different drugs, V82S, G48V, N88D and L90M, showed reduced catalytic activity compared to the wild-type protease on cleavage site peptides, CA-p2, p6pol-PR and PR-RT, critical for viral maturation. 1999 European journal of biochemistry Abstract HIV G48V;L90M;N88D;V82S 91;106;97;85 95;110;101;89 PR;PR;Capsid;PR;PR;RT 17;172;208;221;228;231 25;180;210;223;230;233 10429209 Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. The crystal structures of R8Q, K45I and L90M mutants complexed with a CA-p2 analog inhibitor were determined at 2.0, 1.55 and 1.88 A resolution, respectively, and compared to the wild-type structure. 1999 European journal of biochemistry Abstract HIV K45I;L90M;R8Q 31;40;26 35;44;29 Capsid 70 72 10429209 Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. The mutants D30N and V82S were similar to wild-type protease in their stability toward urea denaturation, while R8Q, G48V, and L90M showed 1.5 to 2.7-fold decreased stability, and N88D and K45I showed 1.6 to 1.7-fold increased stability. 1999 European journal of biochemistry Abstract HIV D30N;G48V;K45I;L90M;N88D;R8Q;V82S 12;117;189;127;180;112;21 16;121;193;131;184;115;25 PR 52 60 10432679 Resistance profiles of (+)2'-deoxy-3'-oxa-4'-thiocytidine and (-)2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. Cloning and sequencing of the RT genes of the selected viruses identified two mutations, M184I for (+) dOTC and M184V for (-) dOTFC. 1999 Nucleosides & nucleotides Abstract HIV M184I;M184V 89;112 94;117 RT 30 32 10432681 Structural determinants of HIV-1 reverse transcriptase stereoselectivity towards (beta)-L-deoxy- and dideoxy-pyrimidine nucleoside triphosphates: molecular basis for the combination of L-dideoxynucleoside analogs with non-nucleoside inhibitors in anti HIV chemotherapy. We have compared the HIV-1 RT mutants containing the single substitutions L100I, K103N, V106A, V179D, Y181I and Y188L, known to confer NNI-resistance in treated patients, to HIV-1 RT wt for their sensitivity towards inhibition by D- and L-deoxy- and dideoxy-nucleoside tiphosphates. 1999 Nucleosides & nucleotides Abstract HIV K103N;L100I;V106A;V179D;Y181I;Y188L 81;74;88;95;102;112 86;79;93;100;107;117 RT;RT 27;180 29;182 10441120 Backbone dynamics of the N-terminal domain of the HIV-1 capsid protein and comparison with the G94D mutant conferring cyclosporin resistance/dependence. The N-terminal domain of a CA mutant (G94D) that confers both resistance to and dependence on cyclosporin A analogues was also analyzed. 1999 Biochemistry Abstract HIV G94D 38 42 Capsid 27 29 10449287 Increased polymerase fidelity of lamivudine-resistant HIV-1 variants does not limit their evolutionary potential. CONCLUSION: This study demonstrates that the Met184Val and Met184Ile mutations in the HIV-1 reverse transcriptase enzyme do not significantly affect the evolutionary potential of the corresponding viruses. 1999 AIDS (London, England) Abstract HIV M184I;M184V 59;45 68;54 RT 92 113 10449287 Increased polymerase fidelity of lamivudine-resistant HIV-1 variants does not limit their evolutionary potential. DESIGN AND METHOD: In vitro selection experiments with either wild-type or lamivudine-resistant viruses (Met184Val and Met184Ile) were performed using a protease inhibitor as the selective drug. 1999 AIDS (London, England) Abstract HIV M184I;M184V 119;105 128;115 PR 153 161 10449287 Increased polymerase fidelity of lamivudine-resistant HIV-1 variants does not limit their evolutionary potential. Met184Val and Met184Ile, result in an increase in polymerase fidelity of the enzyme as measured in biochemical assays; however, the effect of such changes on the fidelity during viral replication is largely unknown. 1999 AIDS (London, England) Abstract HIV M184I;M184V 14;0 23;9 Pol 50 60 10452615 Drug resistance mutations can effect dimer stability of HIV-1 protease at neutral pH. An autolysis-resistant mutant, Q7K/L33I/L63I, was used to facilitate sedimentation equilibrium studies at neutral pH where the wild-type enzyme is typically unstable in the absence of bound inhibitor. 1999 Protein science Abstract HIV L33I;L63I;Q7K 35;40;31 39;44;34 10452615 Drug resistance mutations can effect dimer stability of HIV-1 protease at neutral pH. Sedimentation equilibrium studies were also carried out on several drug-resistant HIV-1 protease mutants: V82F, V82F/I84V, V82T/I84V, and L90M. 1999 Protein science Abstract HIV I84V;I84V;L90M;V82F;V82F;V82T 117;128;138;106;112;123 121;132;142;110;116;127 PR 88 96 10452615 Drug resistance mutations can effect dimer stability of HIV-1 protease at neutral pH. Similar studies using the catalytically inactive D25N mutant yielded a KD value of 1.0 microM at pH 7.0. 1999 Protein science Abstract HIV D25N 49 53 10458616 Abacavir and mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, have profound and synergistic anti-HIV activity. An HIV strain encoding the M184V mutation was susceptible to the combination of MA and abacavir. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 27 32 Matrix 80 82 10465070 Activity of non-nucleoside reverse transcriptase inhibitors against HIV-2 and SIV. Drug-resistant HIV-2 (EHO) variants containing the Ser102Leu and/or Glu219Asp mutations in their RT were selected after passaging the virus in MT-4 cells in the presence of increasing concentrations of delavirdine. 1999 AIDS (London, England) Abstract HIV E219D;S102L 68;51 77;60 RT 97 99 10468556 Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. However, comparison of crystal structures of M184I mutant and wild-type HIV-1 RT with and without DNA reveals repositioning of the template-primer in the M184I/DNA binary complex and other smaller changes in residues in the dNTP-binding site. 1999 Proc Natl Acad Sci U S A Abstract HIV M184I;M184I 45;154 50;159 RT 78 80 10468556 Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. On the basis of these structural results, we developed a model that explains the ability of the 3TC-resistant mutant M184I to incorporate dNTPs but not the nucleotide analog 3TCTP. 1999 Proc Natl Acad Sci U S A Abstract HIV M184I 117 122 10468556 Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Repositioning of the template-primer as observed in the binary complex (M184I/DNA) may also occur in the catalytic ternary complex (M184I/DNA/3TCTP) and contribute to 3TC resistance by interfering with the formation of a catalytically competent closed complex. 1999 Proc Natl Acad Sci U S A Abstract HIV M184I;M184I 132;72 137;76 10468556 Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. We have determined crystal structures of the 3TC-resistant mutant HIV-1 RT (M184I) in both the presence and absence of a DNA/DNA template-primer. 1999 Proc Natl Acad Sci U S A Abstract HIV M184I 76 81 RT 72 74 10475184 Transmission of antiretroviral-drug-resistant HIV-1 variants. Primary-resistance mutations associated with protease inhibitors (V82A, L90M) were detected in three (4%) of 70 individuals; two of these had also RTI-resistance mutations. 1999 Lancet (London, England) Abstract HIV L90M;V82A 72;66 76;70 PR;RT 45;147 53;150 10480631 The rabbit study: ritonavir and saquinavir in combination in saquinavir-experienced and previously untreated patients. In this study, both phenotypic resistance to ritonavir and presence of the L90M mutation predicted the viral load response to ritonavir-saquinavir. 1999 AIDS research and human retroviruses Abstract HIV L90M 75 79 10480631 The rabbit study: ritonavir and saquinavir in combination in saquinavir-experienced and previously untreated patients. There was strong correlation between phenotypic resistance to RIT and the presence of the L90M mutation. 1999 AIDS research and human retroviruses Abstract HIV L90M 90 94 10480632 Rapid screening of phenotypic resistance to nevirapine by direct analysis of HIV type 1 reverse transcriptase activity in plasma. Phenotypic resistance was seen in eight samples obtained after 1 week of treatment and was correlated with detection of the Y181C mutation. 1999 AIDS research and human retroviruses Abstract HIV Y181C 124 129 10480632 Rapid screening of phenotypic resistance to nevirapine by direct analysis of HIV type 1 reverse transcriptase activity in plasma. Preteatment samples and those obtained during the first 6 days of therapy (n = 21) were sensitive to nevirapine, and none had detectable Y181C mutation. 1999 AIDS research and human retroviruses Abstract HIV Y181C 137 142 10482597 Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. In replication kinetics assays, mutant Leu74Val replicated slower than the mutant Met184Val. 1999 Journal of virology Abstract HIV L74V;M184V 39;82 47;91 10482597 Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. The replication kinetics and RT processivity of the mutant with the Leu74Val mutation were compared to those of a lamivudine-selected mutant Met184Val. 1999 Journal of virology Abstract HIV L74V;M184V 68;141 76;150 RT 29 31 10482597 Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. These observations provide biochemical evidence of decreased processivity to support the decrease in replication fitness observed with the Leu74Val or Met184Val mutations. 1999 Journal of virology Abstract HIV L74V;M184V 139;151 147;160 10482597 Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. This work has been extended by showing that a recombinant virus with the HXBc2 backbone and reverse transcriptase (RT) fragments from pNL4-3 containing the Leu74Val mutation produce decreasing amounts of p24 antigen over a 3-week period. 1999 Journal of virology Abstract HIV L74V 156 164 RT;p24;RT 92;204;115 113;207;117 10482597 Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. When the virion-associated RT containing the Leu74Val mutation was used in an RT processivity assay with homopolymer RNA template-primer, poly(A), and oligo(dT), the RT with altered Leu74Val mutation was less processive, generating fewer cDNA products in comparison to wild-type pNL4-3 RT. 1999 Journal of virology Abstract HIV L74V;L74V 45;182 53;190 RT;RT;RT;RT 27;78;166;286 29;80;168;288 10488107 New human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) mutants with increased fidelity of DNA synthesis. Accuracy, template binding, and processivity. In contrast, D76V RT, which also increases fidelity (Kim et al., 1996), showed a 6- to 7-fold increased affinity. 1999 The Journal of biological chemistry Abstract HIV D76V 13 17 RT 18 20 10488107 New human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) mutants with increased fidelity of DNA synthesis. Accuracy, template binding, and processivity. Interestingly, R78A RT exhibited 6- to 8-fold decreases in binding affinity (K(d)) for RNA and DNA templates relative to wild type RT. 1999 The Journal of biological chemistry Abstract HIV R78A 15 19 RT;RT 20;131 22;133 10488107 New human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) mutants with increased fidelity of DNA synthesis. Accuracy, template binding, and processivity. Mutant R78A RT showed reduced primer extension in misincorporation assays lacking a complementary dNTP and exhibited a 9-fold decrease in mutation frequency in the M13mp2 lacZ forward mutation assay. 1999 The Journal of biological chemistry Abstract HIV R78A 7 11 RT 12 14 10488107 New human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) mutants with increased fidelity of DNA synthesis. Accuracy, template binding, and processivity. The processivity of R78A RT on both RNA and DNA templates was substantially reduced relative to wild type RT, whereas the processivity of D76V RT was increased. 1999 The Journal of biological chemistry Abstract HIV D76V;R78A 138;20 142;24 RT;RT;RT 25;106;143 27;108;145 10493275 Adefovir dipivoxil. The drug was most effective in patients with baseline isolates containing the M184V lamivudine resistance mutation according to data from a virological substudy of a large placebo-controlled trial. 1999 Drugs Abstract HIV M184V 78 83 10497170 Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. However, a primer extension assay with three dNTPs showed that F227A generally displays higher fidelity than the wild type RT. 1999 The Journal of biological chemistry Abstract HIV F227A 63 68 RT 123 125 10497170 Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. Interestingly, mutant F227A displayed high fidelity for dG:dA and dC:dA mismatches but low fidelity for dA:dA misinsertions. 1999 The Journal of biological chemistry Abstract HIV F227A 22 27 10497170 Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. Mutant W229A exhibited high fidelity and did not produce a dG:dA or dC:dA mismatch. 1999 The Journal of biological chemistry Abstract HIV W229A 7 12 10497170 Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. Mutants E224A, P225A, P226A, L228A, and E233A were approximately equal to the wild type in their ability to extend the mismatch. 1999 The Journal of biological chemistry Abstract HIV E224A;E233A;L228A;P225A;P226A 8;40;29;15;22 13;45;34;20;27 10497170 Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. Mutants F227A, W229A, M230A, G231A, and Y232A extended 40, 66, 54, 72, and 76% less efficiently past a dG:dA mismatch compared with the wild type. 1999 The Journal of biological chemistry Abstract HIV F227A;G231A;M230A;W229A;Y232A 8;29;22;15;40 13;34;27;20;45 10497170 Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. This indicates that F227A discriminates against particular base substitutions. 1999 The Journal of biological chemistry Abstract HIV F227A 20 25 10497170 Mutations in the primer grip region of HIV reverse transcriptase can increase replication fidelity. We also examined the misinsertion rates of dG, dC, or dA across from a DNA template dA using RT mutants F227A and W229A. 1999 The Journal of biological chemistry Abstract HIV F227A;W229A 104;114 109;119 RT 93 95 10501117 Reduced antiretroviral drug susceptibility among patients with primary HIV infection. Population-based sequence analysis of these 3 samples identified multidrug-resistance mutations in reverse transcriptase (M184V, T215Y, K219K/R) and protease (L101/V, K20R, M361, M46I, G48V, L63P, A71T, V771, V82T, 184V, L90M) in the 2 latter patient samples, along with numerous polymorphisms. 1999 JAMA Abstract HIV A71T;G48V;K20R;K219K;K219R;L63P;L90M;M184V;M46I;T215Y;V82T 197;185;167;136;136;191;221;122;179;129;209 201;189;171;143;143;195;225;127;183;134;213 RT;PR 99;149 120;157 10502270 Rapid development of genotypic resistance to lamivudine when combined with zidovudine in pregnancy. However, four of five women in the dual therapy arm had the M184V mutation in the reverse transcriptase gene associated with decreased susceptibility to lamivudine at delivery. 1999 Journal of medical virology Abstract HIV M184V 60 65 RT 82 103 10505122 Suppression of HIV-1 transcription and replication by a Vpr mutant. Accordingly, a Vpr mutant virus containing the transition of arginine to serine at position 73 exhibited an inhibitory effect on the replication of wild-type virus. 1999 Gene therapy Abstract HIV R73S 61 94 Vpr 15 18 10505122 Suppression of HIV-1 transcription and replication by a Vpr mutant. Our results revealed that alterations of amino acids within the LR domain at position 73 from arginine to serine, renders Vpr defective in stimulating transcription of the viral promoter in human T-lymphocytic and astrocytic cells. 1999 Gene therapy Abstract HIV R73S 86 112 Vpr 122 125 10505677 Rapid detection of the HIV type 1 reverse transcriptase codon T215Y by reverse transcription-polymerase chain reaction with fluorogenic probes. We describe a technique for the detection of the T215Y mutation using reverse transcription-polymerase chain reaction (RT-PCR) amplification of viral sequences and a 5' nuclease assay requiring fluorogenic probes. 1999 AIDS research and human retroviruses Abstract HIV T215Y 49 54 RT;Pol;RT 70;92;119 91;102;121 10508028 In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues. After 16 passages, the virus (HIV-1(P16)) was less sensitive to QYL-685 (104-fold), QYL-609 (>41-fold), and (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC) (>1, 100-fold) than was HIV-1(LAI) and contained an M184I mutation. 1999 Antimicrobial agents and chemotherapy Abstract HIV M184I 205 210 10508028 In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues. However, in the presence of QYL-685 (4 microM), HIV-1(M184I) and HIV-1(M184V) showed greater fitness than HIV-1(wt). 1999 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V 54;71 59;76 10508028 In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues. These data may provide structural and virological relevance with regard to the emergence of M184I and M184V substitutions in HIV-1. 1999 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V 92;102 97;107 10508028 In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues. Two infectious clones, HIV-1(M184I) and HIV-1(M184V), were resistant to QYL-685, QYL-609, and 3TC, confirming that the M184I mutation was responsible for the observed resistance. 1999 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184I;M184V 119;29;46 124;34;51 10508028 In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues. Viral-fitness analyses (competitive HIV-1 replication assays) revealed that in the absence of drugs, M184I and M184V conferred a replication disadvantage on the virus compared to the replication efficiency of the wild-type infectious clone (HIV-1(wt)). 1999 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V 101;111 106;116 10509572 Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group. Among the 39 subjects, 18 (46%) developed mutations: one developed the Val75Thr/Ala mutation, four (10%) developed a Gln151Met multidrug-resistance mutation (MDR), associated in one of them with the Phe77Leu and the Phe116Tyr MDR mutations and 14 (36%) developed one or more zidovudine-specific mutations (Met41Leu, Asp67Asn, Lys70Arg, Leu210Trp, Thr215Tyr/Phe). 1999 AIDS (London, England) Abstract HIV D67N;F116Y;F77L;K70R;L210W;M41L;Q151M;T215F;T215Y;V75A;V75T 316;216;199;326;336;306;117;347;347;71;71 324;225;207;334;345;314;126;360;360;83;83 Asp 316 319 10509572 Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group. RESULTS: At baseline, mutations associated with zidovudine resistance were detected in plasma from two patients: Asp67Asn/Lys219Gln and Leu210Trp. 1999 AIDS (London, England) Abstract HIV D67K;D67N;D67Q;K219Q;L210W 113;113;113;122;136 121;121;121;131;145 Asp 113 116 10509572 Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group. The development of a Met41Leu zidovudine-specific mutation was associated with the development of a Gln151Met mutation in one patient. 1999 AIDS (London, England) Abstract HIV M41L;Q151M 21;100 29;109 10509923 N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1. HI-445 was also tested against the RT Y181C mutant A17 strain of HIV-1 and found to be >7-fold more effective than trovirdine and >1,400-fold more effective than nevirapine or delavirdine. 1999 Bioorganic & medicinal chemistry letters Abstract HIV Y181C 38 43 RT 35 37 10509923 N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1. Similarly, both HI-346 and HI-445 were more effective than trovirdine, nevirapine, and delavirdine against the problematic NNI-resistant HIV-1 strain A17-variant with both Y181C and K103N mutations in RT, although their activity was markedly reduced against this strain. 1999 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 182;172 187;177 RT 201 203 10509923 N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1. Surprisingly, the lead compounds HI-346 and HI-445 were 3-times more effective against the multidrug resistant HIV-1 strain RT-MDR with a V106A mutation (as well as additional mutations involving the RT residues 74V,41L, and 215Y) than they were against HTLV(IIIB) with wild-type RT. 1999 Bioorganic & medicinal chemistry letters Abstract HIV V106A 138 143 RT;RT;RT 124;200;280 126;202;282 10514284 Synthesis and structure-activity relationships of the (alkylamino)piperidine-containing BHAP class of non-nucleoside reverse transcriptase inhibitors: effect of 3-alkylpyridine ring substitution. The synthesis of analogues in which the usual 3-alkylamino substituent on the pyridine ring is replaced by a 3-alkyl substituent led to compounds which retained activity against recombinant P236L and wild-type (WT) reverse transcriptase (RT), while inhibition of the Y181C mutant RT was reduced relative to the activity of the 3-alkylamino-substituted congeners. 1999 Journal of medicinal chemistry Abstract HIV P236L;Y181C 190;267 195;272 RT;RT;RT 215;238;280 236;240;282 10534734 Mutations conferring resistance to zidovudine diminish the antiviral effect of stavudine plus didanosine. Twelve patients had mutations associated with zidovudine resistance (3 T215Y - M41L - L210W; 3 T215Y - M41L; 2 T215Y - L210W; 3 T215Y; 1 K70R) and 1 patient had a multi-dideoxynucleoside resistance mutation (QI5IM). 1999 Journal of medical virology Abstract HIV L210W;L210W;M41L;M41L 86;119;79;103 91;124;83;107 10543890 Pyrrolobenzoxazepinone derivatives as non-nucleoside HIV-1 RT inhibitors: further structure-activity relationship studies and identification of more potent broad-spectrum HIV-1 RT inhibitors with antiviral activity. Compared with the lead 6 and nevirapine, several of the synthesized compounds (PBOs 13a-d and PPOs 13i-k) displayed higher inhibitory activity against wild-type RT and clinically relevant mutant RTs containing the single amino acid substitutions L100I, K103N, V106A, Y181I, and Y188L. 1999 Journal of medicinal chemistry Abstract HIV K103N;L100I;V106A;Y181I;Y188L 253;246;260;267;278 258;251;265;272;283 RT;RT 161;195 163;198 10547288 SH3 domains with high affinity and engineered ligand specificities targeted to HIV-1 Nef. Some of these high-affinity RRT-SH3 domains resembled Hck-SH3 in that they bound much less well to a Nef variant containing an engineered F90R mutation that interferes with docking of the native Hck RT-loop. 1999 Journal of molecular biology Abstract HIV F90R 138 142 Nef;RT 101;199 104;201 10551735 The reverse transcriptase codon 69 insertion is observed in nucleoside reverse transcriptase inhibitor-experienced HIV-1-infected individuals, including those without prior or concurrent zidovudine therapy. CONCLUSIONS: Six-basepair insertions occurred in virus from 4 of 121 (3%) NRTI-experienced subjects, including those without prior ZDV treatment, and was observed in the absence of the T215Y mutation. 1999 Journal of human virology Abstract HIV T215Y 185 190 NRTI 74 78 10551735 The reverse transcriptase codon 69 insertion is observed in nucleoside reverse transcriptase inhibitor-experienced HIV-1-infected individuals, including those without prior or concurrent zidovudine therapy. The T69S mutation and the 6-bp insertion following RT codon 69 were the only RT mutations observed in the 2 subjects with a history of D4T-based therapy. 1999 Journal of human virology Abstract HIV T69S 4 8 RT;RT 51;77 53;79 10551858 Uniquely altered DNA replication fidelity conferred by an amino acid change in the nucleotide binding pocket of human immunodeficiency virus type 1 reverse transcriptase. In contrast to the higher fidelity at most sites, R72A RT is highly error-prone for misincorporations opposite template T in the sequence context: 5'-CTGG. 1999 The Journal of biological chemistry Abstract HIV R72A 50 54 RT 55 57 10551858 Uniquely altered DNA replication fidelity conferred by an amino acid change in the nucleotide binding pocket of human immunodeficiency virus type 1 reverse transcriptase. R72A reverse transcriptase is a frameshift and base substitution antimutator polymerase whose increased fidelity results both from increased nucleotide selectivity and from a decreased ability to extend mismatched primer termini. 1999 The Journal of biological chemistry Abstract HIV R72A 0 4 RT;Pol 5;77 26;87 10551858 Uniquely altered DNA replication fidelity conferred by an amino acid change in the nucleotide binding pocket of human immunodeficiency virus type 1 reverse transcriptase. We show here that replacement of Arg(72) by alanine strongly alters fidelity in a highly unusual manner. 1999 The Journal of biological chemistry Abstract HIV R72A 32 51 10565938 Mutation patterns of the reverse transcriptase and protease genes in human immunodeficiency virus type 1-infected patients undergoing combination therapy: survey of 787 sequences. In 96% of RT genes, a mutation at codon 70 (most frequently, K70R) was associated with a wild-type genotype at position 210 (P < 10(-5)). 1999 Journal of clinical microbiology Abstract HIV K70R 61 65 RT 10 12 10565938 Mutation patterns of the reverse transcriptase and protease genes in human immunodeficiency virus type 1-infected patients undergoing combination therapy: survey of 787 sequences. Similarly, a mutation at codon 210 (most frequently, L210W) was generally associated with mutations at codons 41 (92%) and 215 (96%) but not at codon 219 (16%) or codon 70 (4%) (P < 10(-5)). 1999 Journal of clinical microbiology Abstract HIV L210W 53 58 10574178 Structure-based design of non-nucleoside reverse transcriptase inhibitors of drug-resistant human immunodeficiency virus. HI-236 was more potent than trovirdine, MKC-442 and zidovudine against the drug-sensitive HIV-1 strain IIIB, 50-100 times more effective than delavirdine or nevirapine and twice as effective as our recently reported lead compound N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240) against the NNI-resistant Y181C mutant HIV-1 strain A17. 1999 Antiviral chemistry & chemotherapy Abstract HIV Y181C 324 329 10579814 Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants. Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus. 1999 Journal of medicinal chemistry Abstract HIV K103N;Y181C 152;90 161;99 10579814 Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants. Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys. 1999 Journal of medicinal chemistry Abstract HIV Y181C 208 217 RT 54 56 10582878 Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. A research program targeted toward the identification of expanded-spectrum nonnucleoside reverse transcriptase inhibitors which possess increased potency toward K103N-containing mutant human immunodeficiency virus (HIV) and which maintain pharmacokinetics consistent with once-a-day dosing has resulted in the identification of the 4-cyclopropylalkynyl-4-trifluoromethyl-3, 4-dihydro-2(1H)quinazolinones DPC 961 and DPC 963 and the 4-cyclopropylalkenyl-4-trifluoromethyl-3, 4-dihydro-2(1H)quinazolinones DPC 082 and DPC 083 for clinical development. 1999 Antimicrobial agents and chemotherapy Abstract HIV K103N 161 166 NNRTI 75 110 10582878 Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. DPC 961, DPC 963, DPC 082, and DPC 083 all exhibit low-nanomolar potency toward wild-type virus, K103N and L100I single-mutation variants, and many multiply amino acid-substituted HIV type 1 mutants. 1999 Antimicrobial agents and chemotherapy Abstract HIV K103N;L100I 97;107 102;112 10585459 The motif D loop of human immunodeficiency virus type 1 reverse transcriptase is critical for nucleoside 5'-triphosphate selectivity. Both RT(K220Q) and the chimeric RT are resistant in vitro to 3'-deoxy 3'-azidothymidine 5'-triphosphate (AZTTP). 1999 The Journal of biological chemistry Abstract HIV K220Q 8 13 RT;RT 5;32 7;34 10595550 Real-time measurements of dark substrate catalysis. The method was applied to HIV-1 protease and to the V82F/I84V drug resistant mutant enzyme. 1999 Protein science Abstract HIV I84V;V82F 57;52 61;56 PR 32 40 10617082 N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1. HI-443 inhibited the replication of the NNI-resistant HIV-1 strain A17 variant with Y181C plus K103N mutations in RT with an IC50 value of 3.3 microM, whereas the IC50 values of trovirdine, nevirapine, and delavirdine were all >100 microM. 1999 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 95;84 100;89 RT 114 116 10617082 N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1. HI-443 was almost as potent against the NNI-resistant HIV-1 strain A17 with a Y181C mutation as it was against HTLV(IIIB). 1999 Bioorganic & medicinal chemistry letters Abstract HIV Y181C 78 83 10617082 N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1. The thiophene-ethyl thiourea (TET) compound N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea (compound HI-443) was five times more potent than trovirdine, 1250 times more potent than nevirapine, 100 times more potent than delavirdine, 75 times more potent than MKC-442, and 50 times more potent than AZT against the multidrug resistant HIV-1 strain RT-MDR with a V106A mutation. 1999 Bioorganic & medicinal chemistry letters Abstract HIV V106A 373 378 RT 359 361 10617626 Site-specific incorporation of nucleoside analogs by HIV-1 reverse transcriptase and the template grip mutant P157S. Template interactions influence substrate recognition at the polymerase active site. Incorporation of FTC and 3TC monophosphate varied up to 10-fold opposite 7 different G residues in the DNA template, and the P157S mutation altered this site specificity. 2000 The Journal of biological chemistry Abstract HIV P157S 125 130 10617626 Site-specific incorporation of nucleoside analogs by HIV-1 reverse transcriptase and the template grip mutant P157S. Template interactions influence substrate recognition at the polymerase active site. To characterize better the effects of RT/template interactions on dNTP substrate recognition, we examined the sensitivity of human immunodeficiency virus type 1 (HIV-1) RT containing a new mutation in a "template grip" residue (P157S) to the 5'-triphosphates of (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC), (-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC), and 3'-azido-3'-deoxythymidine (AZT). 2000 The Journal of biological chemistry Abstract HIV P157S 228 233 RT;RT 38;169 40;171 10617626 Site-specific incorporation of nucleoside analogs by HIV-1 reverse transcriptase and the template grip mutant P157S. Template interactions influence substrate recognition at the polymerase active site. When averaged over multiple template sites, P157S RT was 2-7-fold resistant to the 5'-triphosphates of 3TC, FTC, and AZT. 2000 The Journal of biological chemistry Abstract HIV P157S 44 49 RT 50 52 10617626 Site-specific incorporation of nucleoside analogs by HIV-1 reverse transcriptase and the template grip mutant P157S. Template interactions influence substrate recognition at the polymerase active site. Wild-type and P157S RTs had similar catalytic activities and processivities on heteropolymeric RNA and DNA templates. 2000 The Journal of biological chemistry Abstract HIV P157S 14 19 RT 20 23 10618125 Quantitation of human immunodeficiency virus type 1 group O load in plasma by measuring reverse transcriptase activity. The rebound in levels of RT activity was associated with the detection of phenotypic resistance to lamivudine and with the Met184Val mutation. 2000 Journal of clinical microbiology Abstract HIV M184V 123 132 RT 25 27 10622039 Efavirenz: resistance and cross-resistance. K103N is found in HIV strains isolated from patients experiencing a viral rebound in plasma HIV-RNA levels who have received an efavirenz-containing regimen. 1999 International journal of clinical practice. Supplement Abstract HIV K103N 0 5 10622039 Efavirenz: resistance and cross-resistance. Phenotypic analysis showed that the K103N mutation alone confers an approximate 20-fold increase in the IC50 of efavirenz. 1999 International journal of clinical practice. Supplement Abstract HIV K103N 36 41 10622039 Efavirenz: resistance and cross-resistance. With regard to NNRTIs, a single mutation at K103N is the most predominant resistance RT mutation observed with the NNRTIs and confers cross-resistance between efavirenz, nevirapine and delavirdine. 1999 International journal of clinical practice. Supplement Abstract HIV K103N 44 49 NNRTI;NNRTI;RT 15;115;85 21;121;87 10623740 A cell-line-specific defect in the intracellular transport and release of assembled retroviral capsids. High Five cells expressing wild-type Mason-Pfizer monkey virus (M-PMV) Gag precursors accumulate assembled immature capsids in large cytoplasmic aggregates similar to a transport-defective mutant (MA-A18V). 2000 Journal of virology Abstract HIV A18V 200 204 Capsid;Gag;Matrix 116;71;197 123;74;199 10623740 A cell-line-specific defect in the intracellular transport and release of assembled retroviral capsids. In contrast, a larger fraction of the Gag molecules encoded by the M-PMV C-type morphogenesis mutant (MA-R55W) and those of human immunodeficiency virus were transported to the plasma membrane for assembly and budding of virions. 2000 Journal of virology Abstract HIV R55W 105 109 Gag;Matrix 38;102 41;104 10623768 High-level resistance to 3'-azido-3'-deoxythimidine due to a deletion in the reverse transcriptase gene of human immunodeficiency virus type 1. A further increase in resistance (up to 1, 813-fold) was observed when two mutations associated with nonnucleoside RT inhibitor resistance (K103N and L74I) were added to the deletion T69G K70R T215F K219Q construct. 2000 Journal of virology Abstract HIV K103N;K219Q;K70R;L74I;T215F;T69G 140;199;188;150;193;183 146;204;192;154;198;187 RT 115 117 10623768 High-level resistance to 3'-azido-3'-deoxythimidine due to a deletion in the reverse transcriptase gene of human immunodeficiency virus type 1. However, in the context of the T69G mutation and three other mutations known to be associated with AZT resistance (K70R, T215F, and K219Q), this deletion led to a increase in AZT resistance from 8. 2000 Journal of virology Abstract HIV K219Q;K70R;T215F;T69G 132;115;121;31 137;119;126;35 10623768 High-level resistance to 3'-azido-3'-deoxythimidine due to a deletion in the reverse transcriptase gene of human immunodeficiency virus type 1. It has persisted for more than 3 years in association with the accumulation of a variety of other well-described drug resistance mutations and an uncharacterized mutation at RT codon 69 (T69G). 2000 Journal of virology Abstract HIV T69G 187 191 RT 174 176 10625514 Yeast two-hybrid assay for examining human immunodeficiency virus protease heterodimer formation with dominant-negative inhibitors and multidrug-resistant variants. Dimer formation between wt monomers with catalytic aspartates was not detected in yeast, whereas the dimerization of PR monomers harboring the acid active site substitution D25N was readily demonstrated. 2000 Analytical biochemistry Abstract HIV D25N 173 177 PR 117 119 10625514 Yeast two-hybrid assay for examining human immunodeficiency virus protease heterodimer formation with dominant-negative inhibitors and multidrug-resistant variants. The use of inactive monomers harboring the D25N substitution as a genetic background for studying additional HIV PR mutations allowed for the probing of interactions between monomers with mdr-associated mutations with those based on the HIV-1 HXB2R sequence. 2000 Analytical biochemistry Abstract HIV D25N 43 47 PR 113 115 10625668 Requirement of calmodulin binding by HIV-1 gp160 for enhanced FAS-mediated apoptosis. A point mutation in the C-terminal calmodulin-binding domain of gp160 (alanine 835 to tryptophan, A835W) eliminates gp160-dependent enhanced FAS-mediated apoptosis in transiently transfected cells, as well as in vitro calmodulin binding to a peptide corresponding to the C-terminal calmodulin-binding domain of gp160. 2000 The Journal of biological chemistry Abstract HIV A835W 98 103 gp160;gp160;gp160 64;116;311 69;121;316 10634203 Drug resistance mutations among HIV-1 strains from antiretroviral-naive patients in Martinique, French West Indies. Mutant strains L74V (didanosine [ddI] and dideoxycytidine [ddC]) were detected in 3 patients and M184V (lamivudine/ddI/ddC) in 4 patients. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L74V;M184V 15;97 19;102 10634203 Drug resistance mutations among HIV-1 strains from antiretroviral-naive patients in Martinique, French West Indies. One carried both mutations T215Y and M41L known to confer a high degree of phenotypic resistance to ZDV. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M41L;T215Y 37;27 41;32 10634203 Drug resistance mutations among HIV-1 strains from antiretroviral-naive patients in Martinique, French West Indies. ZDV resistance mutations T215Y/F, M41L, and K70R were found in 2, 5, and 12 individuals, respectively. 1999 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M41L;T215F;T215Y 44;34;25;25 48;38;32;32 10634336 Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilege (Agence Nationale de Recherches sur le SIDA 072) Study Team). Of controls, M184V was detected in 11 of 13 S1 plasma samples and in 10 of 11 S2 plasma samples. 2000 JAMA Abstract HIV M184V 13 18 10634336 Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilege (Agence Nationale de Recherches sur le SIDA 072) Study Team). RESULTS: Only 1 primary resistance mutation, M184V, was detected in S1 plasma samples from 4 of 6 patients in the triple-drug and in all 22 in the zidovudine-lamivudine therapy groups and in S2 plasma samples from 3 of 6 in the triple-drug and 20 of 21 in the zidovudine-lamivudine groups. 2000 JAMA Abstract HIV M184V 45 50 10644348 Prophylactic and therapeutic benefits of short-term 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) administration to newborn macaques following oral inoculation with simian immunodeficiency virus with reduced susceptibility to PMPA. No reversion to wild-type susceptibility or loss of the K65R mutation was detected in virus isolates from any of the PMPA-treated or untreated SIVmac055-infected animals. 2000 Journal of virology Abstract HIV K65R 56 60 10644348 Prophylactic and therapeutic benefits of short-term 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) administration to newborn macaques following oral inoculation with simian immunodeficiency virus with reduced susceptibility to PMPA. SIVmac055 is a virulent isolate that has a fivefold-reduced in vitro susceptibility to PMPA, associated with a K65R mutation and additional amino acid changes (N69T, R82K, A158S, S211N) in reverse transcriptase (RT). 2000 Journal of virology Abstract HIV A158S;K65R;N69T;R82K;S211N 172;111;160;166;179 177;115;164;170;184 RT;RT 189;212 210;214 10644351 Involvement of both the V2 and V3 regions of the CCR5-tropic human immunodeficiency virus type 1 envelope in reduced sensitivity to macrophage inflammatory protein 1alpha. The env sequence analyses revealed that the variants had amino acid substitutions in V2 (valine 166 to methionine) and V3 (serine 303 to glycine), although the same V3 substitution appeared in virus passaged without MIP-1alpha. 2000 Journal of virology Abstract HIV S303G;V166M 123;89 144;113 Env 4 7 10656788 Selection of amino acid substitutions restoring activity of HIV-1 integrase mutated in its catalytic site using the yeast Saccharomyces cerevisiae. IN mutants were produced by random PCR mutagenesis in an IN gene bearing the inactivating D116A mutation in the catalytic site. 2000 Journal of molecular biology Abstract HIV D116A 90 95 IN;IN 0;57 2;59 10656788 Selection of amino acid substitutions restoring activity of HIV-1 integrase mutated in its catalytic site using the yeast Saccharomyces cerevisiae. The corresponding D116A substituted IN does not lead to lethality in yeast. 2000 Journal of molecular biology Abstract HIV D116A 18 23 IN 36 38 10656788 Selection of amino acid substitutions restoring activity of HIV-1 integrase mutated in its catalytic site using the yeast Saccharomyces cerevisiae. The three mutants presented restoration of the in vitro strand transfer activity, while 3' processing was only partially restored.The three mutants differ from D116A IN by at least one amino acid substitution located in the N-terminal domain of the protein, outside of the active site. 2000 Journal of molecular biology Abstract HIV D116A 160 165 IN 166 168 10658585 Synthesis and anti-HIV activity of 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs): a new family of HIV-1 specific non-nucleoside reverse transcriptase inhibitors. Some of the test compounds exhibited antiviral activity against L100I RT mutant virus, but significantly lost antiviral activity against K103N, V106A, E138K, Y181C and Y188H RT mutant viruses. 1999 Bioorganic & medicinal chemistry Abstract HIV E138K;K103N;L100I;V106A;Y181C;Y188H 151;137;64;144;158;168 156;142;69;149;163;173 RT;RT 70;174 72;176 10669331 Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine-lamivudine-ritonavir: genotypic analysis of human immunodeficiency virus type 1 isolates from AIDS clinical trials group protocol 315.ACTG Protocol 315 Team. Presence of the K70R mutation was associated with significantly higher plasma HIV-1 RNA levels at baseline. 2000 The Journal of infectious diseases Abstract HIV K70R 16 20 10677212 Helical interactions in the HIV-1 gp41 core reveal structural basis for the inhibitory activity of gp41 peptides. The Gln 652 to Leu mutation leads to a marginal stabilization of the six-helix bundle by -0.8 kcal/mol, evaluated from thermal unfolding experiments. 2000 Biochemistry Abstract HIV Q652L 4 18 10677212 Helical interactions in the HIV-1 gp41 core reveal structural basis for the inhibitory activity of gp41 peptides. To define the basis for this enhanced membrane fusion activity, we investigate the role of the Gln 652 to Leu substitution on the conformation, stability, and biological activity of the N34(L6)C28 model of the gp41 ectodomain core. 2000 Biochemistry Abstract HIV Q652L 95 109 gp41 210 214 10681319 A novel human immunodeficiency virus type 1 reverse transcriptase mutational pattern confers phenotypic lamivudine resistance in the absence of mutation 184V. Combined genotypic and phenotypic analyses of clinical isolates revealed the presence of moderate levels of phenotypic resistance (between 4- and 50-fold) to 3TC in a subset of isolates that did not harbor the M184V mutation. 2000 Antimicrobial agents and chemotherapy Abstract HIV M184V 210 215 10681319 A novel human immunodeficiency virus type 1 reverse transcriptase mutational pattern confers phenotypic lamivudine resistance in the absence of mutation 184V. Mutational cluster analysis and comparison with the phenotypic data revealed a significant correlation between moderate phenotypic 3TC resistance and an increased incidence of replacement of glutamic acid by aspartic acid or alanine and of valine by isoleucine at residues 44 and 118 of reverse transcriptase, respectively. 2000 Antimicrobial agents and chemotherapy Abstract HIV V44I 240 275 RT 287 308 10681319 A novel human immunodeficiency virus type 1 reverse transcriptase mutational pattern confers phenotypic lamivudine resistance in the absence of mutation 184V. We describe a new human immunodeficiency virus type 1 (HIV-1) mutational pattern associated with phenotypic resistance to lamivudine (3TC) in the absence of the characteristic replacement of methionine by valine at position 184 (M184V) of reverse transcriptase. 2000 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V 229;191 234;227 RT 239 260 10681360 Antiviral activity of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652) against lamivudine-resistant human immunodeficiency virus type 1 in SCID-hu Thy/Liv mice. Oral administration of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652), a nucleoside analog structurally similar to lamivudine (3TC), caused dose-dependent inhibition of viral replication in SCID-hu Thy/Liv mice infected with human immunodeficiency virus type 1 NL4-3 and with an NL4-3 clone containing the M184V mutation in reverse transcriptase that confers resistance to 3TC. 2000 Antimicrobial agents and chemotherapy Abstract HIV M184V 303 308 RT 321 342 10681363 Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260). K103N and Y181C, which confer nonnucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance, were the predominant reverse transcriptase mutations. 2000 Antimicrobial agents and chemotherapy Abstract HIV Y181C;K103N 10;0 15;5 NNRTI;RT;NNRTI 30;123;77 65;144;82 10681363 Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260). P236L, which confers DLV resistance but hypersensitivity to other NNRTIs, developed in <10% of isolates. 2000 Antimicrobial agents and chemotherapy Abstract HIV P236L 0 5 NNRTI 66 72 10682135 Diminished HIV-1 sensitivity to stavudine in patients on prolonged therapy occurs only at low levels and cannot be attributed to any single amino acid substitution in reverse transcriptase. Whereas changes in the reverse transcriptase (RT) genes of resistant isolates were frequently observed, two mutations, previously identified with stavudine resistance in tissue culture (i.e., V75T and I50T), could not be identified in the clinical samples by either direct sequencing of the RT gene or by PCR amplification. 1998 Antiviral therapy Abstract HIV I50T;V75T 201;192 205;196 RT;RT;RT 23;46;291 44;48;293 10682139 Loss of lamivudine resistance in a zidovudine and lamivudine dual-resistant HIV-1 isolate after discontinuation of in vitro lamivudine drug pressure. We examined the in vitro phenotypic and genotypic profiles of an extensively passaged human immunodeficiency virus type 1 clinical isolate which has been selected for lamivudine resistance, with an M184V mutation in a zidovudine-resistant genetic background, and then cultured with zidovudine alone. 1998 Antiviral therapy Abstract HIV M184V 198 203 10682151 Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study. CONCLUSIONS: M184V-mediated zidovudine resensitization of HIV-1 is transient in most patients who are given zidovudine/lamivudine combination therapy when zidovudine resistance has already emerged. 1999 Antiviral therapy Abstract HIV M184V 13 18 10682151 Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study. Zidovudine resensitization (related to acquisition of the M184V mutation) was transient, with evolution towards dual resistance to zidovudine and lamivudine in 20 of the 29 patients. 1999 Antiviral therapy Abstract HIV M184V 58 63 10682153 In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. In agreement with the cell culture findings, Escherichia coli-expressed K65R RT showed fivefold reduced susceptibility to PMPA diphosphate, the active moiety of PMPA. 1999 Antiviral therapy Abstract HIV K65R 72 76 RT 77 79 10682153 In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Interestingly, lamivudine-resistant viruses expressing the M184V RT mutation showed wild-type to slightly increased susceptibility to PMPA in vitro and addition of the M184V mutation to HIV with the K65R mutation resulted in reversion to wild-type susceptibility for PMPA. 1999 Antiviral therapy Abstract HIV K65R;M184V;M184V 199;59;168 203;64;173 RT 65 67 10682153 In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Sequence analysis of the reverse transcriptase (RT) genes from four of 15 RT clones demonstrated the presence of a K65R substitution in RT and recombinant HIV expressing the K65R RT mutation showed a threefold to fourfold increase in IC50 value for PMPA as compared to wild-type. 1999 Antiviral therapy Abstract HIV K65R;K65R 115;174 119;178 RT;RT;RT;RT;RT 25;48;74;136;179 46;50;76;138;181 10682159 Different outcome in the first two patients with an HIV-1 multinucleoside drug-resistant T69SSS insertion in Spain. Herein, we report the first two patients in Spain carrying viral populations with the 69-SS insert coupled to the T69S mutation. 1999 Antiviral therapy Abstract HIV T69S 114 118 10682159 Different outcome in the first two patients with an HIV-1 multinucleoside drug-resistant T69SSS insertion in Spain. The presence of the T69SSS complex was confirmed by sequence analysis. 1999 Antiviral therapy Abstract HIV T69SSS 20 26 10684624 Human immunodeficiency virus type 1 reverse transcriptase dimer destabilization by 1-[Spiro[4"-amino-2",2" -dioxo-1",2" -oxathiole-5",3'-[2', 5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]]]-3-ethylthy mine. TSAOe(3)T was unable to destabilize the subunit interactions of the E138K mutant enzyme, which exhibits significant resistance to TSAOe(3)T inhibition. 2000 Biochemistry Abstract HIV E138K 68 73 10704338 Proline residues in the HIV-1 NH2-terminal capsid domain: structure determinants for proper core assembly and subsequent steps of early replication. Entry assays monitoring the process of viral DNA synthesis led to the classification of selected provirus mutants into four different phenotypes: (i) mutant P225L was infectious and allowed complete reverse transcription including formation of 2-LTR circles; (ii) mutants P149L, P170L, and P217L failed to form 2-LTR circles; (iii) mutant P222L displayed a severe defect in binding and incorporating cyclophilin A into virions, was delayed with respect to DNA polymerization, and failed to form a 2-LTR replication intermediate; and (iv) mutant P133L was unable even to synthesize a first-strand cDNA product. 2000 Virology Abstract HIV P133L;P149L;P170L;P217L;P222L;P225L 545;272;279;290;339;157 550;277;284;295;344;162 RT;LTR;LTR;LTR 199;246;313;499 220;249;316;502 10704338 Proline residues in the HIV-1 NH2-terminal capsid domain: structure determinants for proper core assembly and subsequent steps of early replication. However, although the released particles contained wild-type levels of genomic viral RNA, the mature products of the Gag and Gag-Pol polyproteins as well as the Env glycoproteins-all of them, except mutant P225L-were either noninfectious or severely affected in their replicative capacity. 2000 Virology Abstract HIV P225L 206 211 GagPol;Env;Gag 125;161;117 132;164;120 10708276 Non-nucleoside reverse transcriptase inhibitor resistance among patients failing a nevirapine plus protease inhibitor-containing regimen. Although there is a high degree of cross-resistance among NNRTI, nearly one third of resistant isolates carrying the single Y181C mutation remain susceptible to efavirenz. 2000 AIDS (London, England) Abstract HIV Y181C 124 129 NNRTI 58 63 10708276 Non-nucleoside reverse transcriptase inhibitor resistance among patients failing a nevirapine plus protease inhibitor-containing regimen. For isolates containing the single amino acid substitution Y181C, 29% remained fully susceptible to efavirenz, whereas 14% showed intermediate resistance to efavirenz and delavirdine. 2000 AIDS (London, England) Abstract HIV Y181C 59 64 10708276 Non-nucleoside reverse transcriptase inhibitor resistance among patients failing a nevirapine plus protease inhibitor-containing regimen. In the genotypic analysis, the Y181 C mutation was observed in 76% of mutants, and the most common changes were a combination of mutations at positions Y181C/K103N (23%) and the single mutation Y181C (15%). 2000 AIDS (London, England) Abstract HIV K103N;Y181C;Y181C;Y181C 158;31;152;194 163;37;157;199 10708277 Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine. Furthermore, the emergence of these mutations and of the Q151 M multinucleoside resistance complex raise concerns for potential nucleoside analog cross-resistance. 2000 AIDS (London, England) Abstract HIV Q151M 57 63 10708277 Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine. Mutations classically associated with zidovudine resistance were observed to emerge in 7 out of 36 isolates, T215Y/F (four), M41L +T215Y/F (two) and D67N (one). 2000 AIDS (London, England) Abstract HIV D67N;M41L;T215F;T215F;T215Y;T215Y 149;125;109;131;109;131 153;129;116;138;116;138 10708277 Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine. Other mutations observed included the A62V, V751, F77L, F116Y, Q151 M multinucleoside resistance complex (one), the Q151M mutation (two) and the rare V75T mutation (two). 2000 AIDS (London, England) Abstract HIV A62V;F116Y;F77L;Q151M;Q151M;V75T 38;56;50;63;116;150 42;61;54;69;121;154 10708278 Prevalence of HIV-1 resistant to antiretroviral drugs in 81 individuals newly infected by sexual contact or injecting drug use. Investigators of the Quebec Primary Infection Study. The PI mutations, L101, V82A, and L90M, were found in 10.5, 3 and 4% of cases, respectively; whereas for RT, primary mutations at positions T215Y (zidovudine), M184V (lamivudine), T69D/A (zalcitabine), and K103N (multi-NNRTI) were present in 8, 5, 4, and 4% of subjects, respectively. 2000 AIDS (London, England) Abstract HIV K103N;L90M;M184V;T215Y;T69A;T69D;V82A 206;34;160;140;180;180;24 211;38;165;145;186;186;28 NNRTI;PI;RT 219;4;105 224;6;107 10708287 HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. At the latest time point on abacavir monotherapy (range, weeks 6-48), 21 out of 43 subjects harboured virus with resistance conferring mutations including single, double and triple combinations of K65R, L74V, Y115F and M184V. 2000 AIDS (London, England) Abstract HIV K65R;L74V;M184V;Y115F 197;203;219;209 201;207;224;214 10708287 HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. At week 48, 16 out of 46 genotypes were obtained; one of these was wild-type; 15 contained M184V either alone, in combination with K65R and/or L74V and/or Y115F or with thymidine analogue-associated mutations. 2000 AIDS (London, England) Abstract HIV K65R;L74V;M184V;Y115F 131;143;91;155 135;147;96;160 10708287 HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. The most common mutational pattern was L74V + M184V (11/21 cases). 2000 AIDS (London, England) Abstract HIV L74V;M184V 39;46 43;51 10715111 Role of glutamine 151 of human immunodeficiency virus type-1 reverse transcriptase in substrate selection as assessed by site-directed mutagenesis. A natural mutation at codon 151 (Gln --> Met; Q151M) of HIV-1 RT has been shown to confer resistance to the virus against dideoxy nucleoside analogues [Shirasaka, T., et al. 2000 Biochemistry Abstract HIV Q151M 46 51 RT 62 64 10715111 Role of glutamine 151 of human immunodeficiency virus type-1 reverse transcriptase in substrate selection as assessed by site-directed mutagenesis. In contrast, the Q151N mutant was only moderately resistant to ddNTPs but exhibited a higher level of discrimination against rNTPs. 2000 Biochemistry Abstract HIV Q151N 17 22 10715111 Role of glutamine 151 of human immunodeficiency virus type-1 reverse transcriptase in substrate selection as assessed by site-directed mutagenesis. The fidelity of misinsertion was found to be highest for the Q151N mutant followed by Q151M and the wild type enzyme. 2000 Biochemistry Abstract HIV Q151M;Q151N 86;61 91;66 10715111 Role of glutamine 151 of human immunodeficiency virus type-1 reverse transcriptase in substrate selection as assessed by site-directed mutagenesis. To understand its functional implication, we generated two mutant derivatives of this residue (Q151M and Q151N) and examined their sensitivities to ddNTPs and their ability to discriminate against rNTPs versus dNTP substrates on natural U5-PBS HIV-1 RNA template. 2000 Biochemistry Abstract HIV Q151M;Q151N 95;105 101;110 10715111 Role of glutamine 151 of human immunodeficiency virus type-1 reverse transcriptase in substrate selection as assessed by site-directed mutagenesis. We found that Q151M was highly discriminatory against all four ddNTPs but was able to incorporate rNTPs as efficiently as the wild type enzyme. 2000 Biochemistry Abstract HIV Q151M 14 19 10715167 Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. Compound 2 (PNU-32945) was found to have good activity versus wild-type (IC(50) = 2.3 microM) and delavirdine-resistant P236L (IC(50) = 1.1 microM) reverse transcriptase (RT). 2000 Journal of medicinal chemistry Abstract HIV P236L 120 125 RT;RT 148;171 169;173 10715167 Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. Furthermore, this compound was significantly more active versus the P236L mutant than delavirdine. 2000 Journal of medicinal chemistry Abstract HIV P236L 68 73 10715167 Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. In particular, the 3-hydroxyethyl-4-ethyl congener 29 is a potent inhibitor of the P236L mutant (IC(50) = 0.65 microM), whereas it is essentially inactive versus the wild-type enzyme (IC(50) > 50 microM). 2000 Journal of medicinal chemistry Abstract HIV P236L 83 88 10720512 Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group. A total of 51% of subjects showed new mutations at any of codons K65R, L74V, and M184V after abacavir monotherapy, compared with 11% who received zidovudine/abacavir. 2000 The Journal of infectious diseases Abstract HIV K65R;L74V;M184V 65;71;81 69;75;86 10720512 Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group. Abacavir alone in vitro selected for mutations at HIV RT codons K65R, L74V, Y115F, and M184V. 2000 The Journal of infectious diseases Abstract HIV K65R;L74V;M184V;Y115F 64;70;87;76 68;74;92;81 RT 54 56 10720512 Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group. Abacavir therapy in vivo resulted in large decreases in HIV load (>1 log), even in 1 subject who had the M184V mutation at baseline. 2000 The Journal of infectious diseases Abstract HIV M184V 105 110 10720512 Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group. However, abacavir combined with zidovudine selected against virus with the M184V mutation. 2000 The Journal of infectious diseases Abstract HIV M184V 75 80 10723499 Sensitivity and resistance to (+)-calanolide A of wild-type and mutated forms of HIV-1 reverse transcriptase. In contrast, the Y188H substitution in RT resulted in about 30-fold resistance to (+)-calanolide A in these assays but did not result in diminished sensitivity to nevirapine. 1999 Antiviral therapy Abstract HIV Y188H 17 22 RT 39 41 10723499 Sensitivity and resistance to (+)-calanolide A of wild-type and mutated forms of HIV-1 reverse transcriptase. We found that RT containing either the V106A or Y181C substitutions, associated with NNRTI resistance, displayed approximately 90-fold resistance to nevirapine but remained fully sensitive to (+)-calanolide A and that the Y181C mutation marginally enhanced susceptibility to the latter drug. 1999 Antiviral therapy Abstract HIV V106A;Y181C;Y181C 39;48;222 44;53;227 NNRTI;RT 85;14 90;16 10729133 The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. Pyrophosphorolysis on 3TC-terminated primer strands was not detectable with M184V-containing, as opposed to wild-type, RT, and rescue of AZT-terminated DNA synthesis was significantly decreased with the former enzyme. 2000 Journal of virology Abstract HIV M184V 76 81 RT 119 121 10729133 The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. The present study demonstrates that the M184V mutation, which confers high-level resistance to 3TC, can severely compromise the removal of chain-terminating nucleotides. 2000 Journal of virology Abstract HIV M184V 40 45 10729133 The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. These results are consistent with tissue culture and clinical data showing sustained antiviral effects of AZT in the context of viruses that contain the M184V mutation in the RT-encoding gene. 2000 Journal of virology Abstract HIV M184V 153 158 RT 175 177 10734063 Mechanism by which phosphonoformic acid resistance mutations restore 3'-azido-3'-deoxythymidine (AZT) sensitivity to AZT-resistant HIV-1 reverse transcriptase. High level AZT resistance requires multiple mutations (D67N/K70R/T215F/K219Q). 2000 The Journal of biological chemistry Abstract HIV D67N;K219Q;K70R;T215F 55;71;60;65 59;76;64;70 10734063 Mechanism by which phosphonoformic acid resistance mutations restore 3'-azido-3'-deoxythymidine (AZT) sensitivity to AZT-resistant HIV-1 reverse transcriptase. In order to characterize the mechanism of PFA resistance-mediated resensitization to AZT, the A114S mutation associated with PFA resistance was introduced into the reverse transcriptase (RT) of both wild type and drug-resistant virus. 2000 The Journal of biological chemistry Abstract HIV A114S 94 99 RT;RT 164;187 185;189 10734063 Mechanism by which phosphonoformic acid resistance mutations restore 3'-azido-3'-deoxythymidine (AZT) sensitivity to AZT-resistant HIV-1 reverse transcriptase. Introduction of A114S into the AZT resistance background significantly diminishes both the enhanced pyrophosphorolytic activity and the DNA synthesis processivity associated with the AZT-resistant RT. 2000 The Journal of biological chemistry Abstract HIV A114S 16 21 RT 197 199 10734063 Mechanism by which phosphonoformic acid resistance mutations restore 3'-azido-3'-deoxythymidine (AZT) sensitivity to AZT-resistant HIV-1 reverse transcriptase. The A114S mutation also alters the nucleotide-dependent phosphorolysis activity associated with AZT resistance. 2000 The Journal of biological chemistry Abstract HIV A114S 4 9 10734063 Mechanism by which phosphonoformic acid resistance mutations restore 3'-azido-3'-deoxythymidine (AZT) sensitivity to AZT-resistant HIV-1 reverse transcriptase. The decrease in phosphorolytic activity of RT conferred by the PFA resistance A114S mutation resensitizes AZT-resistant HIV-1 to AZT by allowing the latter to again function as a chain terminator of viral DNA synthesis. 2000 The Journal of biological chemistry Abstract HIV A114S 78 83 RT 43 45 10734063 Mechanism by which phosphonoformic acid resistance mutations restore 3'-azido-3'-deoxythymidine (AZT) sensitivity to AZT-resistant HIV-1 reverse transcriptase. The presence of the A114S mutation therefore severely impairs the mutant enzyme's ability to excise chain-terminating AZT. 2000 The Journal of biological chemistry Abstract HIV A114S 20 25 10737786 Analysis of mutations at positions 115 and 116 in the dNTP binding site of HIV-1 reverse transcriptase. In contrast, the RT variant Tyr-115-Val is significantly impaired in polymerase activity compared with wild-type RT; however, Tyr-115-Val is able to incorporate ribonucleotides as well as deoxyribonucleotides during polymerization and is resistant to a variety of nucleoside analogs. 2000 Proc Natl Acad Sci U S A Abstract HIV Y115V;Y115V 28;126 39;137 Pol;RT;RT 69;17;113 79;19;115 10737786 Analysis of mutations at positions 115 and 116 in the dNTP binding site of HIV-1 reverse transcriptase. The RT variants Tyr-115-Phe and Phe-116-Tyr are similar to wild-type HIV-1 RT in most, but not all, respects. 2000 Proc Natl Acad Sci U S A Abstract HIV F116Y;Y115F 32;16 43;27 RT;RT 4;75 6;77 10739910 An alternate binding site for the P1-P3 group of a class of potent HIV-1 protease inhibitors as a result of concerted structural change in the 80s loop of the protease. Structures of the complexes of HIV protease inhibitor L--756,423 with the HIV-1 wild-type protease and of the inhibitors Indinavir, L-739,622 and Saquinavir with the mutant protease (9X) containing nine point mutations (Leu10Val, Lys20Met, Leu24Ile, Ser37Asp, Met46Ile, Ile54Val, Leu63Pro, Ala71Val, Val82Thr) have been determined. 2000 Acta crystallographica. Section D, Biological crystallography Abstract HIV A71V;I54V;K20M;L10V;L24I;L63P;M46I;S37D;V82T 290;270;230;220;240;280;260;250;300 298;278;238;228;248;288;268;258;308 PR;PR;PR 35;90;173 43;98;181 10747109 Emergence of drug resistance mutations in human immunodeficiency virus type 2-infected subjects undergoing antiretroviral therapy. Moreover, the latter two patients harbored a codon Q151M mutation which is associated to multidrug resistance in HIV-1, and one of these subjects carried some of the typically linked mutations at codons 65 and 69. 2000 Journal of clinical microbiology Abstract HIV Q151M 51 56 10747890 Vertical-scanning mutagenesis of a critical tryptophan in the "minor groove binding track" of HIV-1 reverse transcriptase. Major groove DNA adducts identify specific protein interactions in the minor groove. These lesions failed to block DNA polymerization by wild-type RT, yet the Trp(266) mutants and an alanine mutant of Gly(262) terminated synthesis on styrene oxide-adducted templates. 2000 The Journal of biological chemistry Abstract HIV G262A 98 124 RT 62 64 10748215 Coupling ribose selection to fidelity of DNA synthesis. The role of Tyr-115 of human immunodeficiency virus type 1 reverse transcriptase. However, selectivity of deoxyribonucleotides versus ribonucleotides was not affected in mutants Y115W and F160W. 2000 The Journal of biological chemistry Abstract HIV F160W;Y115W 106;96 111;101 10748215 Coupling ribose selection to fidelity of DNA synthesis. The role of Tyr-115 of human immunodeficiency virus type 1 reverse transcriptase. Mutant RTs with nonconservative substitutions affecting Tyr-115 (Y115V, Y115A, and Y115G) showed a dramatic reduction in their ability to discriminate against ribonucleotides in the presence of both cations. 2000 The Journal of biological chemistry Abstract HIV Y115A;Y115G;Y115V 72;83;65 77;88;70 RT 7 10 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. After adjustment for the assembly and packaging defects, a minor (twofold) reduction in synthesis of either strong-stop, full-length linear DNA or 2-LTR circles was observed with R10A/K11A virions, indicating that reverse transcription and nuclear transport of the viral genome were largely intact. 2000 Journal of virology Abstract HIV K11A;R10A 184;179 188;183 RT;LTR 214;149 235;152 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. Detailed analysis of the replication defect of R10A/K11A revealed a threefold reduction in virion yield and a fivefold reduction in packaging of viral genomic RNA. 2000 Journal of virology Abstract HIV K11A;R10A 52;47 56;51 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. Each of the above-mentioned defects was corrected by introduction of the second-site compensatory mutation E21K. 2000 Journal of virology Abstract HIV E21K 107 111 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. However, after adjustment for the amounts of full-length or 2-LTR circles produced, R10A/K11A virions were at least 10-fold less infectious than wild type, indicating that viral DNA produced by the R10A/K11A mutant failed to integrate. 2000 Journal of virology Abstract HIV K11A;K11A;R10A;R10A 203;89;84;198 207;93;88;202 LTR 62 65 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. Human immunodeficiency type 1 (HIV-1) bearing the nucleocapsid (NC) mutation R10A/K11A is replication defective. 2000 Journal of virology Abstract HIV K11A;R10A 82;77 86;81 NC 64 66 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. It had acquired, in addition, a new mutation (E21K) that was formally demonstrated to be sufficient for restoration of viral replication. 2000 Journal of virology Abstract HIV E21K 46 50 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. The E21K mutation is predicted to restore positive charge to the face of the R10A/K11A mutant NC protein that interacts with the HIV-1 SL3 RNA stem-loop, emphasizing the importance of NC basic residues for HIV-1 replication. 2000 Journal of virology Abstract HIV E21K;K11A;R10A 4;82;77 8;86;81 NC;NC 94;184 96;186 10756042 Rescue of multiple viral functions by a second-site suppressor of a human immunodeficiency virus type 1 nucleocapsid mutation. These results demonstrate that the replication defect of mutant R10A/K11A can be explained by impairment at multiple steps in the viral life cycle, most important among them being integration and RNA packaging. 2000 Journal of virology Abstract HIV K11A;R10A 69;64 73;68 10756056 A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. All viruses that carried the N88S mutation were hypersensitive to amprenavir. 2000 Journal of virology Abstract HIV N88S 29 33 10756056 A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. Site-directed mutagenesis studies confirmed the causal role of N88S in determining amprenavir hypersensitivity. 2000 Journal of virology Abstract HIV N88S 63 67 10756056 A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. The most pronounced increases in susceptibility were strongly associated with an N88S mutation in protease. 2000 Journal of virology Abstract HIV N88S 81 85 PR 98 106 10756056 A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. The presence of the N88S mutation and associated amprenavir hypersensitivity may be useful in predicting an improved clinical response to amprenavir salvage therapy. 2000 Journal of virology Abstract HIV N88S 20 24 10770740 Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. Mutated recombinant molecular clone HXB2D-D67G was further selected with (+)dOTFC, and three of six clones sequenced contained both the D67G and M184V mutations, while the other three of the six clones contained only the D67G mutation. 2000 Antimicrobial agents and chemotherapy Abstract HIV D67G;D67G;D67G;M184V 42;136;221;145 46;140;225;150 10770740 Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. Selection with (+)dOTFC also produced variants which were 10-fold more resistant than the wild type, and a novel mutation, D67G, was identified following cloning and sequencing of the RT genes. 2000 Antimicrobial agents and chemotherapy Abstract HIV D67G 123 127 RT 184 186 10770740 Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. Studies with mutated recombinant HXB2D virus confirmed the importance of the M184V mutation in conferring resistance to (-)dOTFC in MT-4 cells, although no difference in sensitivity was observed in primary cells. 2000 Antimicrobial agents and chemotherapy Abstract HIV M184V 77 82 10770740 Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. The D67G mutation was introduced into HXB2D by site-directed mutagenesis, and the data obtained confirmed the importance of this mutation in conferring resistance to both (+)dOTFC and (-)dOTFC. 2000 Antimicrobial agents and chemotherapy Abstract HIV D67G 4 8 10770740 Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. The dOTFC-resistant variants that were selected were 10-fold less sensitive than wild-type virus, and cloning and sequencing of the complete reverse transcriptase (RT)-coding region identified the mutation M184V. 2000 Antimicrobial agents and chemotherapy Abstract HIV M184V 206 211 RT;RT 141;164 162;166 10770740 Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. The M184V substitution also displayed decreased susceptibility to (+)dOTFC. 2000 Antimicrobial agents and chemotherapy Abstract HIV M184V 4 9 10770770 Susceptibility to PNU-140690 (Tipranavir) of human immunodeficiency virus type 1 isolates derived from patients with multidrug resistance to other protease inhibitors. The mutations included the following: I15V, E35D, N37D, R41K, D60E, and A71T. 2000 Antimicrobial agents and chemotherapy Abstract HIV A71T;D60E;E35D;I15V;N37D;R41K 72;62;44;38;50;56 76;66;48;42;54;60 10770770 Susceptibility to PNU-140690 (Tipranavir) of human immunodeficiency virus type 1 isolates derived from patients with multidrug resistance to other protease inhibitors. The substitutions among the amino acid residues of the protease included L10I, K20R, L24I, M36I, N37D, G48V, I54V, L63P, I64V, A71V, V77I, V82A, I84V, and L90M. 2000 Antimicrobial agents and chemotherapy Abstract HIV A71V;G48V;I54V;I64V;I84V;K20R;L10I;L24I;L63P;L90M;M36I;N37D;V77I;V82A 127;103;109;121;145;79;73;85;115;155;91;97;133;139 131;107;113;125;149;83;77;89;119;159;95;101;137;143 PR 55 63 10775609 Alteration of substrate and inhibitor specificity of feline immunodeficiency virus protease. Mutants containing a I35D or I57G substitution showed no activity against either FIV or HIV substrates. 2000 Journal of virology Abstract HIV I35D;I57G 21;29 25;33 10775609 Alteration of substrate and inhibitor specificity of feline immunodeficiency virus protease. Mutations at Q54K, I98P, and L101I dramatically reduced activity. 2000 Journal of virology Abstract HIV I98P;L101I;Q54K 19;29;13 23;34;17 10775609 Alteration of substrate and inhibitor specificity of feline immunodeficiency virus protease. The I37V, N55M, M56I, V59I, and Q99V mutants yielded full activity. 2000 Journal of virology Abstract HIV I37V;M56I;N55M;Q99V;V59I 4;16;10;32;22 8;20;14;36;26 10775609 Alteration of substrate and inhibitor specificity of feline immunodeficiency virus protease. The I37V, N55M, M56I, V59I, and Q99V mutants, compared with wt FIV protease, all showed inhibitor specificity more similar to that of HIV-1 protease. 2000 Journal of virology Abstract HIV I37V;M56I;N55M;Q99V;V59I 4;16;10;32;22 8;20;14;36;26 PR;PR 67;140 75;148 10775609 Alteration of substrate and inhibitor specificity of feline immunodeficiency virus protease. The I37V, N55M, V59I, and Q99V mutants showed a significant increase in activity against the HIV-1 reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type (wt) FIV protease. 2000 Journal of virology Abstract HIV I37V;N55M;Q99V;V59I 4;10;26;16 8;14;30;20 RT;IN;PR 99;121;202 120;130;210 10775609 Alteration of substrate and inhibitor specificity of feline immunodeficiency virus protease. The I37V, V59I, and Q99V mutants also showed an increase in activity against two rapidly cleaved peptides selected by cleavage of a phage display library with HIV-1 protease. 2000 Journal of virology Abstract HIV I37V;Q99V;V59I 4;20;10 8;24;14 PR 165 173 10775618 Identification of critical amino acid residues in human immunodeficiency virus type 1 IN required for efficient proviral DNA formation at steps prior to integration in dividing and nondividing cells. Mutation at the conserved Tyr 143 (Y143G) resulted in partial impairment of completion of reverse transcription in monocyte-derived macrophages (MDM) but not in rhabdomyosarcoma cells. 2000 Journal of virology Abstract HIV Y143G 35 40 RT 90 111 10775618 Identification of critical amino acid residues in human immunodeficiency virus type 1 IN required for efficient proviral DNA formation at steps prior to integration in dividing and nondividing cells. Similar effects were obtained by introducing a stop codon in the vpr gene (DeltaVpr), and additive effects of both mutations (Y143G plus DeltaVpr) were observed. 2000 Journal of virology Abstract HIV Y143G 126 132 Vpr 65 68 10775618 Identification of critical amino acid residues in human immunodeficiency virus type 1 IN required for efficient proviral DNA formation at steps prior to integration in dividing and nondividing cells. Thus, the possible impairment of Y143G might occur during the nuclear transport of the PIC. 2000 Journal of virology Abstract HIV Y143G 33 38 10776836 Nelfinavir: an update on its use in HIV infection. Nelfinavir primarily selects for the D30N mutation, which is not seen with other protease inhibitors, and alone does not cause resistance to other protease inhibitors in vitro. 2000 Drugs Abstract HIV D30N 37 41 PR;PR 81;147 89;155 10777142 Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors. Abacavir plus GW420867X selected only for NNRTI-specific mutations (i.e., K101E, K103R, V106A, and Y181C), including the novel L100V mutation. 2000 AIDS research and human retroviruses Abstract HIV K101E;K103R;L100V;V106A;Y181C 74;81;127;88;99 79;86;132;93;104 NNRTI 42 47 10777142 Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors. Combination of GW420867X with five different NNRTIs selected solely for NNRTI-specific mutations, and also for the L100V mutation in the combined presence of efavirenz, nevirapine, or emivirine, respectively. 2000 AIDS research and human retroviruses Abstract HIV L100V 115 120 NNRTI;NNRTI 45;72 51;77 10777142 Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors. Lamivudine plus GW420867X selected for the 3TC-specific M184I mutation and a number of NNRTI-characteristic mutations (i.e., V106A, V108I, and Y188H). 2000 AIDS research and human retroviruses Abstract HIV M184I;V106A;V108I;Y188H 56;125;132;143 61;130;137;148 NNRTI 87 92 10777143 Baseline HIV type 1 genotypic resistance to a newly added nucleoside analog is predictive of virologic failure of the new therapy. This difference was particularly striking for patients with the baseline M184V mutation and whose treatment was modified by the addition of lamivudine. 2000 AIDS research and human retroviruses Abstract HIV M184V 73 78 10785387 Fidelity analysis of HIV-1 reverse transcriptase mutants with an altered amino-acid sequence at residues Leu74, Glu89, Tyr115, Tyr183 and Met184. Conversely, the ddI-resistant RT mutant containing the Leu74-->Val mutation showed a 3.5-fold higher fidelity compared to the wild-type enzyme. 2000 European journal of biochemistry Abstract HIV L74V 55 66 RT 30 32 10785387 Fidelity analysis of HIV-1 reverse transcriptase mutants with an altered amino-acid sequence at residues Leu74, Glu89, Tyr115, Tyr183 and Met184. Finally, the Tyr115-->Ala substitution rendered the enzyme substantially more error-prone for DNA polymerization. 2000 European journal of biochemistry Abstract HIV Y115A 13 25 10785387 Fidelity analysis of HIV-1 reverse transcriptase mutants with an altered amino-acid sequence at residues Leu74, Glu89, Tyr115, Tyr183 and Met184. For the 3TC-resistant Met184-->Val RT mutant an almost wild-type level of overall mutation frequency was observed, while the foscarnet-resistant RTs harbouring the Glu89-->Gly mutation showed only a twofold decrease in mutation frequency. 2000 European journal of biochemistry Abstract HIV E89G;M184V 164;22 175;34 RT;RT 35;145 37;148 10785387 Fidelity analysis of HIV-1 reverse transcriptase mutants with an altered amino-acid sequence at residues Leu74, Glu89, Tyr115, Tyr183 and Met184. The Tyr183-->Phe mutant RT displayed a slightly lower fidelity than wild-type RT. 2000 European journal of biochemistry Abstract HIV T183P 4 16 RT;RT 24;78 26;80 10785387 Fidelity analysis of HIV-1 reverse transcriptase mutants with an altered amino-acid sequence at residues Leu74, Glu89, Tyr115, Tyr183 and Met184. We found that the reported higher fidelity of nucleotide incorporation by the Met184-->Val and Glu89-->Gly mutant reverse transcriptases (RTs) was not reflected in a substantial increase in the overall fidelity for these RT mutants. 2000 European journal of biochemistry Abstract HIV E89G;M184V 95;78 106;90 RT;RT;RT 114;138;221 136;141;223 10792990 Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. Especially high levels of resistance to zidovudine were observed for viruses with a beta3-beta4 insertion in the background of A62V, L210W, and T215Y. 2000 Virology Abstract HIV A62V;L210W;T215Y 127;133;144 131;138;149 10792990 Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. Finally, we observed a genome with a deletion of codon 70 associated with a Q151M MDR mutation. 2000 Virology Abstract HIV Q151M 76 81 10792990 Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. In 9 cases, the insertion was associated with a D67S, G, or E mutation. 2000 Virology Abstract HIV D67S 48 52 10792990 Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. In addition, we identified 13 (2.1%) viruses harboring specific MDR mutations (mainly Q151M and/or A62V, V75I, F116Y). 2000 Virology Abstract HIV A62V;F116Y;Q151M;V75I 99;111;86;105 103;116;91;109 10792990 Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. Interestingly, the A62V mutation was found in 6 of the 15 strains with an insertion, whereas the other MDR mutations were not observed in insertion mutant strains. 2000 Virology Abstract HIV A62V 19 23 10792990 Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. These include a cluster of five mutations in the reverse-transcriptase (RT) coding region (A62V, V75I, F77L, F116Y, and Q151M) generally referred to as multidrug resistance (MDR) mutations, and insertions of one or several amino acid residues between codons 67 and 70 of RT, a flexible region joining two antiparrallel beta sheets (beta3-beta4 insertions). 2000 Virology Abstract HIV A62V;F116Y;F77L;Q151M;V75I 91;109;103;120;97 95;114;107;125;101 RT;RT;RT 49;72;271 70;74;273 10794716 Mutational analysis of Lys65 of HIV-1 reverse transcriptase. Furthermore, the K65A, K65Q and K65E mutant enzymes are 100-fold less sensitive to all dideoxynucleoside triphosphate ('ddNTP') inhibitors, whereas the K65R mutation results in a selective 10-fold decrease in binding of ddCTP and ddATP only. 2000 The Biochemical journal Abstract HIV K65A;K65E;K65Q;K65R 17;32;23;152 21;36;27;156 10794716 Mutational analysis of Lys65 of HIV-1 reverse transcriptase. In order to biochemically define the function of RT Lys(65), we have used site-specific mutagenesis to generate RT with a variety of substitutions at this position, including K65E, K65Q, K65A and K65R. 2000 The Biochemical journal Abstract HIV K65A;K65E;K65Q;K65R 187;175;181;196 191;179;185;200 RT;RT 49;112 51;114 10794716 Mutational analysis of Lys65 of HIV-1 reverse transcriptase. In particular, Glu in K65E can form a salt bridge with Arg(72), leading to the diminution of the latter residue's interaction with the alpha-phosphate of the dNTP residue. 2000 The Biochemical journal Abstract HIV K65E 22 26 10794716 Mutational analysis of Lys65 of HIV-1 reverse transcriptase. The pH optimum for the DNA polymerase activity of K65E RT was 6.5, compared to 7.5 for the wild-type enzyme, and 8.0 for the K65R, K65A and K65Q mutants. 2000 The Biochemical journal Abstract HIV K65A;K65E;K65Q;K65R 131;50;140;125 135;54;144;129 Pol;RT 27;55 37;57 10797372 Prevalence of drug resistant mutants and virological response to combination therapy in patients with primary HIV-1 infection. Two percent (1/48) had a major mutation associated with resistance to protease inhibitors (D30N). 2000 Journal of medical virology Abstract HIV D30N 91 95 PR 70 78 10799614 Convergent evolution of reverse transcriptase (RT) genes of human immunodeficiency virus type 1 subtypes E and B following nucleoside analogue RT inhibitor therapies. Particularly, identical amino acid substitutions were present simultaneously at four different positions (D67N, K70R, T215F, and K219Q) for high-level AZT resistance. 2000 Journal of virology Abstract HIV D67N;K219Q;K70R;T215F 106;129;112;118 110;134;116;123 10807188 Specific recognition of lamivudine-resistant HIV-1 by cytotoxic T lymphocytes. Furthermore, this demonstrates that the immune system can generate new CTL specificities even in patients with advanced disease, as the M184V HIV variants emerges only after drug treatment. 2000 AIDS (London, England) Abstract HIV M184V 136 141 10807188 Specific recognition of lamivudine-resistant HIV-1 by cytotoxic T lymphocytes. OBJECTIVE: The reverse transcriptase (RT) M184V mutation within the HLA-A2-restricted HIV-1 cytotoxic T lymphocyte (CTL) epitope VL9 (VIYQYMDDL; RT 179-187) not only induces drug escape against lamivudine but also abolished recognition by a CTL clone derived from a long-term non-progressor. 2000 AIDS (London, England) Abstract HIV M184V 42 47 RT;RT;RT 15;38;145 36;40;147 10807188 Specific recognition of lamivudine-resistant HIV-1 by cytotoxic T lymphocytes. To test whether the variant VL9 epitope containing the M184V mutation represents a new CTL epitope, we studied recognition of this epitope in a cohort of HLA-A2-positive HIV-1-infected patients. 2000 AIDS (London, England) Abstract HIV M184V 55 60 HIV infections 170 184 10819437 N-[2-(4-methylphenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea as a potent inhibitor of NNRTI-resistant and multidrug-resistant human immunodeficiency virus type 1. Notably, HI-244 was 20 times more effective than trovirdine against the multidrug-resistant HIV-1 strain RT-MDR with a V106A mutation (as well as additional mutations involving the RT residues 74V, 41L and 215Y) and seven times more potent than trovirdine against the NNRTI-resistant HIV-1 strain A17 with a Y181C mutation. 2000 Antiviral chemistry & chemotherapy Abstract HIV V106A;Y181C 119;308 124;313 NNRTI;RT;RT 268;105;181 273;107;183 10819438 Non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis and biological evaluation of novel quinoxalinylethylpyridylthioureas as potent antiviral agents. Several of these novel non-nucleoside RT inhibitors, with a substituted pyrroloquinoxalinone heteroaromatic skeleton, showed inhibitory activity against wild-type RT as well as against mutant RTs containing the single amino acid substitutions L1001, K103N, V106A, Y1811 and Y188L that was much greater than other non-nucleoside inhibitors such as nevirapine. 2000 Antiviral chemistry & chemotherapy Abstract HIV K103N;V106A;Y188L 250;257;274 255;262;279 RT;RT;RT 38;163;192 40;165;195 10819983 Valine of the YVDD motif of moloney murine leukemia virus reverse transcriptase: role in the fidelity of DNA synthesis. In the MuLV RT system, the two mutants V223M and V223A exhibited an overall reduced fidelity of DNA synthesis, specifically for RNA-templated reactions. 2000 Biochemistry Abstract HIV V223A;V223M 49;39 54;44 RT 12 14 10821705 Synthesis and evaluation of "AZT-HEPT", "AZT-pyridinone", and "ddC-HEPT" conjugates as inhibitors of HIV reverse transcriptase. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC(50) = 0.45 microM) against HIV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. 2000 Journal of medicinal chemistry Abstract HIV Y181C 128 133 10821705 Synthesis and evaluation of "AZT-HEPT", "AZT-pyridinone", and "ddC-HEPT" conjugates as inhibitors of HIV reverse transcriptase. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 microM anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. 2000 Journal of medicinal chemistry Abstract HIV Y181C 172 177 10825158 Identification of residues of CXCR4 critical for human immunodeficiency virus coreceptor and chemokine receptor activities. The coreceptor activity of CXCR4 was markedly impaired by mutations of two Tyr residues in NT (Y7A/Y12A) or at a single Asp residue in ECL2 (D193A), ECL3 (D262A), or TMII (D97N). 2000 The Journal of biological chemistry Abstract HIV D193A;D262A;D97N;Y12A;Y7A 141;155;172;99;95 146;160;176;103;98 Asp 120 123 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. An in vitro dNTP exclusion assay revealed an increased fidelity for K65R RT compared with wild-type RT, but little change for L74V RT. 2000 The Journal of biological chemistry Abstract HIV K65R;L74V 68;126 72;130 RT;RT;RT 73;100;131 75;102;133 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) variants with the K65R or L74V substitution display resistance to several nucleoside analogs. 2000 The Journal of biological chemistry Abstract HIV K65R;L74V 89;97 93;101 RT;RT 44;67 65;69 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. It is speculated that the increased fidelity of K65R RT is due to an altered interaction with the dNTP substrate. 2000 The Journal of biological chemistry Abstract HIV K65R 48 52 RT 53 55 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Modeling the substitutions into the x-ray structure of the ternary complex revealed that the major influence of Leu(74) in stabilizing the templating base is unaffected by Val substitution, whereas the K65R substitution appears to increase the stringency of dNTP binding. 2000 The Journal of biological chemistry Abstract HIV K65R 202 206 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Nucleotide sequence analysis of lacZalpha mutants generated by variant RTs indicated that K65R RT displays uniform reduction in most types of errors, whereas L74V RT does not. 2000 The Journal of biological chemistry Abstract HIV K65R;L74V 90;158 94;162 RT;RT;RT 71;95;163 74;97;165 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. The increase in overall fidelity observed for K65R RT is the largest reported for any drug-resistant HIV-1 RT variant. 2000 The Journal of biological chemistry Abstract HIV K65R 46 50 RT;RT 51;107 53;109 10833521 Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. When the forward mutation rates were measured via a gap-filling assay, the K65R variant displayed an 8-fold decrease in the overall mutation rate (1.0 x 10(-3) versus 8.6 x 10(-3) for wild-type HIV-1 RT), whereas the rate for the L74V variant was closer to that for wild-type RT (5.0 x 10(-3)). 2000 The Journal of biological chemistry Abstract HIV K65R;L74V 75;230 79;234 RT;RT 200;276 202;278 10839585 The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. CNA3002 European Study Team. The presence of the M184V mutation did not preclude an antiviral response to ABC; 73% of subjects with the M184V mutation alone experienced a > or = 1.0 log10 copies/ml reduction in plasma HIV-1 RNA or had a value of < or = 400 copies/ml by week 16. 2000 AIDS (London, England) Abstract HIV M184V;M184V 20;107 25;112 10839657 Efavirenz- and adefovir dipivoxil-based salvage therapy in highly treatment-experienced patients: clinical and genotypic predictors of virologic response. Patients with Y181C or G190A single mutations had an initial greater magnitude of viral load suppression than those with K103N, but this advantage was short lived. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G190A;K103N;Y181C 23;121;14 28;126;19 10841542 Analysis of mutations and suppressors affecting interactions between the subunits of the HIV type 1 reverse transcriptase. A primer grip mutation, L234A, previously shown to inhibit RT dimerization by biochemical assays, also prevented RT dimerization in the yeast two-hybrid system. 2000 Proc Natl Acad Sci U S A Abstract HIV L234A 24 29 RT;RT 59;113 61;115 10841542 Analysis of mutations and suppressors affecting interactions between the subunits of the HIV type 1 reverse transcriptase. In vitro binding experiments confirmed the effects of the L234A mutation and the suppressor mutations on the interaction of the two subunits. 2000 Proc Natl Acad Sci U S A Abstract HIV L234A 58 63 10841542 Analysis of mutations and suppressors affecting interactions between the subunits of the HIV type 1 reverse transcriptase. Second-site mutations that restored RT dimerization in yeast to the L234A parent were recovered in the tryptophan repeat region at the dimer interface and at the polymerase active site, suggesting the involvement of these sites in RT dimerization. 2000 Proc Natl Acad Sci U S A Abstract HIV L234A 68 73 Pol;RT;RT 162;36;231 172;38;233 10846594 Frequency of antiretroviral drug resistance mutations in HIV-1 strains from patients failing triple drug regimens. The Terry Beirn Community Programs for Clinical Research on AIDS. Population-based sequence analyses showed that nearly all patients had similar RT gene mutations regardless of prior drug exposure, although the M184V mutation was significantly less prevalent in patients not recently treated with lamivudine. 2000 Antiviral therapy Abstract HIV M184V 145 150 RT 79 81 10858331 In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. Cloning and DNA sequencing of the RT region from the first resistant isolate identified a K65R mutation (AAA to AGA) in 10 of 10 clones. 2000 Antimicrobial agents and chemotherapy Abstract HIV K65R 90 94 RT 34 36 10858331 In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. DNA sequencing of RT clones derived from the second resistant isolate identified the L74V mutation, previously reported to cause ddI resistance. 2000 Antimicrobial agents and chemotherapy Abstract HIV L74V 85 89 RT 18 20 10858331 In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. However, the combination of AZT with DXG or its orally bioavailable prodrug (-)-beta-D-2, 6-diaminopurine-dioxolane should be explored because of the suppressive effects of the K65R and L74V mutations on AZT resistance. 2000 Antimicrobial agents and chemotherapy Abstract HIV K65R;L74V 177;186 181;190 10858331 In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. However, when introduced into a genetic background for AZT resistance (D67N, K70R, T215Y, T219Q), the K65R mutation reversed the AZT resistance. 2000 Antimicrobial agents and chemotherapy Abstract HIV D67N;K65R;K70R;T215Y;T219Q 71;102;77;83;90 75;106;81;88;95 10858331 In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. The K65R mutation also conferred greater than threefold cross-resistance to 2',3'-dideoxycytidine, 2', 3'-dideoxyinosine, 2',3'-dideoxy-3'-thiacytidine, 9-(2-phosphonylmethoxyethyl)adenine, 2-amino-6-chloropurine dioxolane, dioxolanyl-5-fluorocytosine, and diaminopurine dioxolane but had only marginal effects on 3'-azido-3'-deoxthymidine (AZT) susceptibility. 2000 Antimicrobial agents and chemotherapy Abstract HIV K65R 4 8 10858331 In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. The L74V mutation also decreased the AZT resistance when the mutation was introduced into a genetic background for AZT resistance (D67N, K70R, T215Y, T219Q) but to a lesser degree than the K65R mutation did. 2000 Antimicrobial agents and chemotherapy Abstract HIV D67N;K65R;K70R;L74V;T215Y;T219Q 131;189;137;4;143;150 135;193;141;8;148;155 10860720 Sequences within Pr160gag-pol affecting the selective packaging of primer tRNA(Lys3) into HIV-1. While point mutations K249E, K249Q, and R307E in the primer grip region of the thumb subdomain have been reported to inhibit the in vitro interaction of mature reverse transcriptase with the anticodon loop of tRNA(Lys3), we find that these mutations do not inhibit tRNA(Lys3) packaging into the virus, which supports other work indicating that the anticodon loop of tRNA(Lys3) is not involved in interactions with Pr160gag-pol during tRNA(Lys3) packaging. 2000 Journal of molecular biology Abstract HIV K249E;K249Q;R307E 22;29;40 27;34;45 RT;Pol;PR 160;423;414 181;426;416 10861645 Prevalence of primary resistance to zidovudine and lamivudine in drug-naive human immunodeficiency virus type-1 infected patients: high proportion of reverse transcriptase codon 215 mutant in circulating lymphocytes and free virus. Mutation T215Y/F was found in five (5.6%) patients infected between 1994 and 1997, whereas none of these patients harbored the mutation M184V. 2000 Journal of medical virology Abstract HIV M184V;T215F;T215Y 136;9;9 141;16;16 10861645 Prevalence of primary resistance to zidovudine and lamivudine in drug-naive human immunodeficiency virus type-1 infected patients: high proportion of reverse transcriptase codon 215 mutant in circulating lymphocytes and free virus. The presence of primary zidovudine (AZT)-resistance (mutation T215Y/F) or lamivudine (3TC)-resistance (mutation M184V) was evaluated in 90 drug-naive patients infected with human immunodeficiency virus type-1 (HIV-1) between 1987 and 1997. 2000 Journal of medical virology Abstract HIV M184V;T215F;T215Y 112;62;62 117;69;69 10861645 Prevalence of primary resistance to zidovudine and lamivudine in drug-naive human immunodeficiency virus type-1 infected patients: high proportion of reverse transcriptase codon 215 mutant in circulating lymphocytes and free virus. The T215Y/F mutation was present in the virus and/or provirus and persisted for at least two years. 2000 Journal of medical virology Abstract HIV T215F;T215Y 4;4 11;11 10864635 Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. From analysis of the frequency of M184I and M184V mutants determined at multiple time points in seven individuals during lamivudine therapy, we estimated the fitness advantage of M184V over M184I during therapy to be approximately 23% on average. 2000 Journal of virology Abstract HIV M184I;M184I;M184V;M184V 34;190;44;179 39;195;49;184 10864635 Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. Human immunodeficiency virus type 1 (HIV-1) rapidly develops resistance to lamivudine during monotherapy, typically resulting in the appearance at position 184 in reverse transcriptase (RT) of isoleucine instead of the wild-type methionine (M184I) early in therapy, which is later replaced by valine (M184V). 2000 Journal of virology Abstract HIV M184I;M184V 241;301 246;306 RT;RT 163;186 184;188 10864635 Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. M184V reduces viral susceptibility to drug in vitro by approximately 100-fold, but also results in a lower processivity of RT. 2000 Journal of virology Abstract HIV M184V 0 5 RT 123 125 10864635 Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. The timing of emergence of the M184V mutant varies widely between infected individuals. 2000 Journal of virology Abstract HIV M184V 31 36 10864635 Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. We have found that the differences between individuals in the rate of evolution of lamivudine resistance arise due to genetic drift affecting the relative frequency of M184I and M184V prior to therapy. 2000 Journal of virology Abstract HIV M184I;M184V 168;178 173;183 10864635 Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. We show that a drop in absolute viral fitness associated with the outgrowth of M184V results in a drop in viral load only in individuals with high CD4(+) counts, from whom we estimate the relative fitness of M184V in the presence of drug to be approximately 10% of that of the wild type prior to therapy. 2000 Journal of virology Abstract HIV M184V;M184V 79;208 84;213 10864662 Effects of amino acid substitutions at position 115 on the fidelity of human immunodeficiency virus type 1 reverse transcriptase. The effects of Y115V were greater than those of Y115F. 2000 Journal of virology Abstract HIV Y115F;Y115V 48;15 53;20 10864662 Effects of amino acid substitutions at position 115 on the fidelity of human immunodeficiency virus type 1 reverse transcriptase. We compared the fidelity of wild-type human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) and two RT mutants, Y115F and Y115V. 2000 Journal of virology Abstract HIV Y115F;Y115V 129;139 134;144 RT;RT;RT 82;105;117 103;107;119 10864665 Phosphorylation of human immunodeficiency virus type 1 Vpr regulates cell cycle arrest. Mutation of Ser-79 to Ala abrogated effects of Vpr on cell cycle progression, whereas mutation of Ser-94 and Ser-96 had no effect. 2000 Journal of virology Abstract HIV S79A 12 25 Vpr 47 50 10871864 A single point mutation in the nuclear localization domain of Sam68 blocks the Rev/RRE-mediated transactivation. In contrast, we now report that the full length Sam68 protein having the same mutation (Arginine429-->Alanine) is completely localized in the nucleus while another Sam68 (Proline439-->Arginine) mutant is found in the cytoplasm. 2000 Oncogene Abstract HIV P439R;R429A 171;88 192;109 10873473 The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. Both of the mutations, M184I and M184V, provide very high levels of resistance in vivo; purified HIV-1 RT carrying M184V and M184I also shows resistance to 3TCTP and FTCTP in in vitro polymerase assays. 2000 Journal of molecular biology Abstract HIV M184I;M184I;M184V;M184V 23;125;33;115 28;130;38;120 Pol;RT 184;103 194;105 10873473 The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. Structural studies suggest that the mechanism of resistance of HIV-1 RTs carrying the M184V or M184I mutation involves steric hindrance, which could either completely block the binding of 3TCTP and FTCTP or allow binding of these nucleoside triphosphate molecules but only in a configuration that would prevent incorporation. 2000 Journal of molecular biology Abstract HIV M184I;M184V 95;86 100;91 RT 69 72 10873473 The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. The initial change is usually to M184I; this virus is rapidly replaced by a variant carrying the mutation M184V. 2000 Journal of molecular biology Abstract HIV M184I;M184V 33;106 38;111 10873473 The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase. These studies show that both wild-type RT and the drug-resistant variants can bind 3TCTP at the polymerase active site; however, the binding to M184V and M184I is somewhat weaker and is sensitive to salt. 2000 Journal of molecular biology Abstract HIV M184I;M184V 154;144 159;149 Pol;RT 96;39 106;41 10873749 A mutant of Sindbis virus that is resistant to pyrazofurin encodes an altered RNA polymerase. Sequencing of this region identified four mutations (nt 5750, 6627, 7543, and 7593), which are predicted to lead to amino acid changes: opal550L in nsP3 and M287L, K592I, and P609T in nsP4. 2000 Virology Abstract HIV K592I;M287L;P609T 164;157;175 169;162;180 10873749 A mutant of Sindbis virus that is resistant to pyrazofurin encodes an altered RNA polymerase. Using a molecular model of nsP4 based on the structure of HIV reverse transcriptase, we located amino acid change M287L at the tip of the fingers domain and K592I and P609T at the base of the thumb domain of the viral RNA polymerase. 2000 Virology Abstract HIV K592I;M287L;P609T 157;114;167 162;119;172 RT;Pol 62;222 83;232 10875608 Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients. As TSAO derivatives have not been used in the clinical setting, the presence of the E138A mutation at a frequency of 6.7% in our study of 90 TSAO-inexperienced HIV-seropositive individuals implies that 138A of the RT must be a natural variant and that the mutant virus is replication competent. 2000 AIDS research and human retroviruses Abstract HIV E138A 84 89 RT 214 216 10875608 Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients. E138K, not E138A, is a known TSAO-specific resistance mutation, emerging under selective pressure in vitro. 2000 AIDS research and human retroviruses Abstract HIV E138A;E138K 11;0 16;5 10875608 Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients. HIV-1 samples from six patients undergoing diverse anti-HIV therapies possessed the E138A mutation in their reverse transcriptase (RT) genome. 2000 AIDS research and human retroviruses Abstract HIV E138A 84 89 RT;RT 108;131 129;133 10875608 Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients. In addition, we have demonstrated through phenotypic analysis of the E138A and A98S mutants (after in vitro mutagenesis) that the mutation A98S, found in one of these patients, could be partially responsible for the phenotypic reversal of TSAO resistance. 2000 AIDS research and human retroviruses Abstract HIV A98S;A98S;E138A 79;139;69 83;143;74 10875608 Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients. Our observations suggest that the E138A mutation may likely arise in patients under the selective pressure of TSAO or related compounds that show a decreased antiviral potency toward the E138A variant. 2000 AIDS research and human retroviruses Abstract HIV E138A;E138A 34;187 39;192 10875608 Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients. Our phenotypic data on the patient isolates, confirmed by data on an E138A mutant acquired through in vitro mutagenesis, indicated that an alanine substitution for glutamate at codon 138 of the HIV-1 RT renders the virus TSAO resistant, confirming the importance of this amino acid residue in the activity of TSAO derivatives. 2000 AIDS research and human retroviruses Abstract HIV E138A;E138A 69;139 74;186 RT 200 202 10877832 High-level expression of active HIV-1 integrase from a synthetic gene in human cells. Lentiviral vector particles carrying the inactivating D64V mutation in the integrase gene were capable of stably transducing 293T cells when complemented in the producer cells with integrase expressed from the synthetic gene. 2000 FASEB journal Abstract HIV D64V 54 58 IN;IN 75;181 84;190 10877852 Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor 8-Cl TIBO: contribution of the L100I and Y181C variants to protein stability and biological activity. Using Monte Carlo simulations, both free energy perturbation and linear response calculations were carried out for the transformation of wild-type RT to two key mutants, Y181C and L100I. 2000 Protein engineering Abstract HIV L100I;Y181C 180;170 185;175 RT 147 149 10878071 Early virological failure in naive human immunodeficiency virus patients receiving saquinavir (soft gel capsule)-stavudine-zalcitabine (MIKADO trial) is not associated with mutations conferring viral resistance. However, the fact that two patients developed an L90M mutation only 4 weeks after relapse points to the need for genotypic resistance testing in the context of an initial failure of the antiretroviral regimen. 2000 Journal of clinical microbiology Abstract HIV L90M 49 53 10878071 Early virological failure in naive human immunodeficiency virus patients receiving saquinavir (soft gel capsule)-stavudine-zalcitabine (MIKADO trial) is not associated with mutations conferring viral resistance. Reverse transcriptase and protease genotypic analyses in group 1 revealed the acquisition of only one SQV-associated mutation (L90M) in only two patients. 2000 Journal of clinical microbiology Abstract HIV L90M 127 131 RT;PR 0;26 21;34 10878071 Early virological failure in naive human immunodeficiency virus patients receiving saquinavir (soft gel capsule)-stavudine-zalcitabine (MIKADO trial) is not associated with mutations conferring viral resistance. There was no significant increase in the 50 or 90% inhibitory concentration of SQV in patients with or without the L90M mutation. 2000 Journal of clinical microbiology Abstract HIV L90M 115 119 10888639 Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1. In addition, the Y14N mutation specifically reduced the maximum efficiencies of infection that could be obtained at saturating CCR5 concentrations. 2000 Journal of virology Abstract HIV Y14N 17 21 10888639 Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1. The sigmoidal curves for all R5 HIV-1 isolates were quantitatively consistent with a simple mathematical model, implying that CCR5s reversibly associate with cell surface HIV-1 in a concentration-dependent manner, that approximately four to six CCR5s assemble around the virus to form a complex needed for infection, and that both mutations inhibit assembly of this complex but only the Y14N mutation also significantly reduces its ability to successfully mediate HIV-1 infections. 2000 Journal of virology Abstract HIV Y14N 387 391 10888639 Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1. The Y14N mutation converted a YYT sequence at positions 14 to 16 to an NYT consensus site for N-linked glycosylation, and the mutant protein was shown to be glycosylated at that position. 2000 Journal of virology Abstract HIV Y14N 4 8 10888639 Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1. To address these issues, we studied the effects of CCR5 concentrations on HIV-1 infections using wild-type CCR5 and two attenuated mutant CCR5s, one with the mutation Y14N at a critical tyrosine sulfation site in the amino terminus and one with the mutation G163R in extracellular loop 2. 2000 Journal of virology Abstract HIV G163R;Y14N 258;167 263;171 10894274 Evolution of lamivudine-resistant hepatitis B virus and HIV-1 in co-infected individuals: an analysis of the CAESAR study. CAESAR co-ordinating committee. Ten of the thirteen patients had a 44-52 week HIV viral load > 1000 copies/ml, all of whom also had HIV reverse transcriptase M184V or M184I mutations. 2000 AIDS (London, England) Abstract HIV M184I;M184V 135;126 140;131 RT 104 125 10894284 Absence of zidovudine resistance in antiretroviral-naive patients following zidovudine/lamivudine/protease inhibitor combination therapy: virological evaluation of the AVANTI 2 and AVANTI 3 studies. The M184V mutation developed in most ZDV/3TC-treated subjects from both studies. 2000 AIDS (London, England) Abstract HIV M184V 4 9 10894284 Absence of zidovudine resistance in antiretroviral-naive patients following zidovudine/lamivudine/protease inhibitor combination therapy: virological evaluation of the AVANTI 2 and AVANTI 3 studies. The presence of M184V was, however, associated with significantly lower plasma viral RNA levels when compared with values obtained before initiation of treatment. 2000 AIDS (London, England) Abstract HIV M184V 16 21 10894284 Absence of zidovudine resistance in antiretroviral-naive patients following zidovudine/lamivudine/protease inhibitor combination therapy: virological evaluation of the AVANTI 2 and AVANTI 3 studies. There was a high frequency (4 of 11) of the protease L10F substitution in ZDV/3TC/IDV-treated patients that was associated with virological failure but did not result in phenotypic resistance to any of the PIs tested. 2000 AIDS (London, England) Abstract HIV L10F 53 57 PR;PI 44;206 52;209 10898683 Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. and T69S-XX was identified in two of the study samples (0.5%; both of them T69S-SS), but both patterns were absent among control samples. 2000 Antimicrobial agents and chemotherapy Abstract HIV T69S;T69S 4;75 8;79 10898683 Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. Non-NRTI (NNRTI)-related changes were observed in viral strains from two patients, which displayed the Q151M resistance pattern, although the patients were NNRTI naive. 2000 Antimicrobial agents and chemotherapy Abstract HIV Q151M 103 108 NNRTI;NNRTI;NNRTI 0;10;156 8;15;161 10898683 Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. Q151M was identified in six of the study samples (1. 2000 Antimicrobial agents and chemotherapy Abstract HIV Q151M 0 5 10898683 Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. Study samples (n = 363) collected between 1991 and 1997 from patients exposed to two or more nucleoside analogue reverse transcriptase inhibitors (NRTIs) and 274 control samples from patients exposed to no or one NRTI were screened for two marker mutations of multinucleoside resistance (the Q151M mutation and a mutation with a 2-amino-acid insertion at codon 69, T69S-XX). 2000 Antimicrobial agents and chemotherapy Abstract HIV Q151M;T69S 292;365 297;369 NRTI;NRTI;NRTI 93;147;213 134;152;217 10906218 Structural and kinetic analyses of the protease from an amprenavir-resistant human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and resensitized to amprenavir. Passage of the triple-mutant APV-resistant HIV-1 strain in MT4 cells, in the presence of increasing concentrations of saquinavir (SQV), gave rise to a new variant containing M46I, G48V, I50V, and I84L mutations in the protease and a resulting phenotype that was resistant to SQV and, unexpectedly, resensitized to APV. 2000 Journal of virology Abstract HIV G48V;I50V;I84L;M46I 180;186;196;174 184;190;200;178 PR 218 226 10906218 Structural and kinetic analyses of the protease from an amprenavir-resistant human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and resensitized to amprenavir. The protease inhibitor amprenavir (APV) generates a signature set of HIV type 1 (HIV-1) protease mutations associated with in vitro resistance (M46I/L, I47V, and I50V [triple mutant]). 2000 Journal of virology Abstract HIV I47V;I50V;M46I;M46L 152;162;144;144 156;166;150;150 PR;PR 4;88 12;96 10906218 Structural and kinetic analyses of the protease from an amprenavir-resistant human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and resensitized to amprenavir. The switch in protease inhibitor sensitivities resulted from (i) the I50V mutation, which reduced the area of contact with APV and SQV; (ii) the compensating I84L mutation, which improved hydrophobic packing with APV; and (iii) the G-to-V mutation at residue 48, which introduced steric repulsion with the P3 group of SQV. 2000 Journal of virology Abstract HIV I50V;I84L 69;158 73;162 PR 14 22 10915071 Correlation between human immunodeficiency virus genotypic resistance and virologic response in patients receiving nelfinavir monotherapy or nelfinavir with lamivudine and zidovudine. All 6 PR-RT(+) patients had virus with M184V (lamuvidine resistance); 3 isolates also contained D30N (nelfinavir resistance). 2000 The Journal of infectious diseases Abstract HIV D30N;M184V 96;39 100;44 PR;RT 6;9 8;11 10915071 Correlation between human immunodeficiency virus genotypic resistance and virologic response in patients receiving nelfinavir monotherapy or nelfinavir with lamivudine and zidovudine. M184V preceded D30N in all determinable instances. 2000 The Journal of infectious diseases Abstract HIV D30N;M184V 15;0 19;5 10921971 Comparative evaluation of three human immunodeficiency virus genotyping systems: the HIV-GenotypR method, the HIV PRT GeneChip assay, and the HIV-1 RT line probe assay. Only the LiPA identified K70R, a possible transmitted zidovudine resistance mutation, in the RT gene of a treatment-naive patient. 2000 Journal of clinical microbiology Abstract HIV K70R 25 29 RT 93 95 10931842 Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. Interestingly, expression of R73S mutant in cells exerts a negative effect on the observed superactivation of the LTR by Tat, cyclin T1/CDK9, and wild type Vpr. 2000 The Journal of biological chemistry Abstract HIV R73S 29 33 LTR;Vpr;Tat 114;156;121 117;159;124 10931842 Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. Moreover identification of R73S mutant of Vpr provides a new therapeutic avenue for controlling HIV-1 gene transcription and replication in the infected cells. 2000 The Journal of biological chemistry Abstract HIV R73S 27 31 Vpr 42 45 10931842 Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. This activation was not observed with the R73S mutant of Vpr, which contains arginine to serine transition at residue 73. 2000 The Journal of biological chemistry Abstract HIV R73S;R73S 42;77 46;120 Vpr 57 60 10950391 Drug resistance and drug combination features of the human immunodeficiency virus inhibitor, BCH-10652 [(+/-)-2'-deoxy-3'-oxa-4'-thiocytidine, dOTC]. The degree of resistance recorded for dOTC (four- to sevenfold), (-)dOTC (five- to eightfold) and (+)dOTC (five- to >18-fold) against these M1841 or M184V mutants, was significantly less than that recorded for 3TC (>100-fold). 2000 Antiviral chemistry & chemotherapy Abstract HIV M184V 149 154 10952574 In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632. An I84V change appeared to be an important substitution in the third strain used. 2000 Antimicrobial agents and chemotherapy Abstract HIV I84V 3 7 10952574 In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632. Genotypic and phenotypic analysis of three different HIV strains resistant to BMS-232632 indicated that an N88S substitution in the viral protease appeared first during the selection process in two of the three strains. 2000 Antimicrobial agents and chemotherapy Abstract HIV N88S 107 111 PR 138 146 10952598 Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. A K103N substitution was the HIV-1 RT gene mutation most frequently observed among plasma samples from patients for whom combination therapy including efavirenz failed, occurring in at least 90% of cases of efavirenz-indinavir or efavirenz-zidovudine (ZDV)-lamivudine (3TC) treatment failure. 2000 Antimicrobial agents and chemotherapy Abstract HIV K103N 0 7 RT 35 37 10952598 Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. L100I, K101E, K101Q, Y188H, Y188L, G190S, G190A, and G190E mutations were also observed. 2000 Antimicrobial agents and chemotherapy Abstract HIV G190A;G190E;G190S;K101E;K101Q;Y188H;Y188L;L100I 42;53;35;7;14;21;28;0 47;58;40;12;19;26;33;5 10952598 Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. The proportion of patients carrying NNRTI resistance mutations, usually K103N, increased dramatically at the time of initial viral load rebound in cases of treatment failure after exposure to efavirenz. 2000 Antimicrobial agents and chemotherapy Abstract HIV K103N 72 77 NNRTI 36 41 10952598 Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. V106A, Y181C, and Y188C mutations, which have been associated with high levels of resistance to other NNRTIs, were rare in the patient samples in this study, both before and after exposure to efavirenz. 2000 Antimicrobial agents and chemotherapy Abstract HIV Y181C;Y188C;V106A 7;18;0 12;23;5 NNRTI 102 108 10952598 Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. V108I and P225H mutations were observed frequently, predominantly in viral genomes that also contained other nonnucleoside RT inhibitor (NNRTI) resistance mutations. 2000 Antimicrobial agents and chemotherapy Abstract HIV P225H;V108I 10;0 15;5 NNRTI;RT 137;123 142;125 10952598 Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Viruses with multiple, linked NNRTI mutations, especially K103N-V108I and K103N-P225H double mutants, accumulated more slowly following the emergence of K103N mutant viruses. 2000 Antimicrobial agents and chemotherapy Abstract HIV K103N;K103N;K103N;P225H;V108I 58;74;153;80;64 63;79;158;85;69 NNRTI 30 35 10953059 Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetra-acetyl esters. Although inhibition of HIV integrase activity by L-CA and its derivatives was confirmed in an oligonucleotide-driven assay, integrase carrying the G140S mutation was inhibited to the same extent as the wild-type integrase. 2000 Molecular pharmacology Abstract HIV G140S 147 152 IN;IN;IN;Capsid 27;124;212;51 36;133;221;53 10953059 Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetra-acetyl esters. This conclusion was based on the inhibition of integrase activity in enzymatic assays and the isolation of a resistant HIV strain with a mutation (G140S) in the integrase gene. 2000 Molecular pharmacology Abstract HIV G140S 147 152 IN;IN 47;161 56;170 10954539 Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture. In contrast, the Y181C reverse transcriptase demonstrated a selective acceleration of the secondary RNase H cleavage step during both modes of RNase H cleavage. 2000 Journal of virology Abstract HIV Y181C 17 22 RT 23 44 10954539 Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture. Of the NNRTI-resistant mutants, V179D was more fit than Y181C, and both of these mutants were more fit than V106A, which demonstrated the greatest reduction in RNase H cleavage. 2000 Journal of virology Abstract HIV V106A;V179D;Y181C 108;32;56 113;37;61 NNRTI 7 12 10954539 Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture. The V106A reverse transcriptase demonstrated a three- to fourfold slowing of both DNA 3'-end-directed and RNA 5'-end-directed RNase H cleavage relative to both wild-type and V179D enzymes, similar to what was observed for P236L in a previously published study (P. 2000 Journal of virology Abstract HIV P236L;V106A;V179D 222;4;174 227;9;179 RT 10 31 10954539 Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture. Three mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (V106A, V179D, and Y181C), which occur in clinical isolates and confer resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), were analyzed for RNA- and DNA-dependent DNA polymerization and RNase H cleavage. 2000 Journal of virology Abstract HIV V106A;V179D;Y181C 84;91;102 89;96;107 NNRTI;RT;NNRTI 168;61;216 203;82;222 10957718 Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors. A431V and/or L449F were present exclusively among individuals failing PI treatment (17 of 75 [23%] and 3 of 75 [3%], respectively). 2000 AIDS research and human retroviruses Abstract HIV L449F;A431V 13;0 18;5 PI 70 72 10957718 Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors. A431V is selected in association with specific PR inhibitor mutations. 2000 AIDS research and human retroviruses Abstract HIV A431V 0 5 PR 47 49 10957718 Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors. Natural polymorphism P453L might direct the PR resistance pathway through I84V instead of V82 mutation. 2000 AIDS research and human retroviruses Abstract HIV I84V;P453L 74;21 78;26 PR 44 46 10957718 Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors. Natural polymorphism P453L was strongly associated with the selection of PR I84V (OR 49.5; 95% CI 12-212) and selected against V82 mutation (OR 0.15; 95% CI 0.02-1. 2000 AIDS research and human retroviruses Abstract HIV I84V;P453L 76;21 80;26 PR 73 75 10957718 Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors. There was a significant association between A431V and PR M46I,L (OR 13.7; 95% CI 4.2-44.3) and V82A,F,T (OR 8.8; 95% CI 2.7-27.8). 2000 AIDS research and human retroviruses Abstract HIV A431V;M46I;M46L;V82A;V82F;V82T 44;57;57;95;95;95 49;63;63;103;103;103 PR 54 56 10957721 Natural variation in the amino acid sequence around the HIV type 1 glycoprotein 160 cleavage site and its effect on cleavability, subunit association, and membrane fusion. Four constructs derived from two isolates of the same patient showed an unusual gp41 N terminus (gp41, 514G-->P) and a slightly diminished fusion capacity due to a decreased cleavability. 2000 AIDS research and human retroviruses Abstract HIV G514P 103 111 gp41;gp41 80;97 84;101 10957721 Natural variation in the amino acid sequence around the HIV type 1 glycoprotein 160 cleavage site and its effect on cleavability, subunit association, and membrane fusion. One construct displayed significant lowered fusion capacity and had an amino acid exchange in the first position of the gp41 N terminus (gp41, 512A-->S) leading to a decreased association of the SU and TM subunits. 2000 AIDS research and human retroviruses Abstract HIV A512S 143 151 gp41;gp41 120;137 124;141 10958691 CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA. P-TEFb complexes containing a catalytically inactive CDK9 mutant (D167N) bound TAR RNA weakly and independently of ATP, as did a C-terminal truncated CDK9 mutant that was catalytically active but unable to undergo autophosphorylation. 2000 Molecular and cellular biology Abstract HIV D167N 66 71 10958691 CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA. Replacement of CDK9 phosphorylation sites with negatively charged residues restored binding of CycT1(1-303)-D167N-Tat, and rendered D167N a more potent inhibitor of transcription in vitro. 2000 Molecular and cellular biology Abstract HIV D167N;D167N 132;108 137;113 Tat 114 117 10958988 Cell cycle G2 arrest induced by HIV-1 Vpr in fission yeast (Schizosaccharomyces pombe) is independent of cell death and early genes in the DNA damage checkpoint. A strain with a mutation changing the Tyr15 of Cdc2 to the non-phosphorylated Phe (Y15F) eliminated Vpr-induced G2 arrest indicating that Tyr15 of Cdc2 is the sole target for induction of G2 arrest by Vpr. 2000 Virus research Abstract HIV Y15F 83 87 Vpr;Vpr 100;201 103;204 10958988 Cell cycle G2 arrest induced by HIV-1 Vpr in fission yeast (Schizosaccharomyces pombe) is independent of cell death and early genes in the DNA damage checkpoint. Interestingly, Vpr still induces cell death and morphological changes in the Y15F Cdc2 strain indicating that G2 arrest is not required for morphological changes and cell death. 2000 Virus research Abstract HIV Y15F 77 81 Vpr 15 18 10966816 How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease. The crystal structure of an actual HIV-1 protease-substrate complex is presented at 2.0 A resolution (R-value of 19.7 % (R(free) 23.3 %)) between an inactive variant (D25N) of HIV-1 protease and a long substrate peptide, Lys-Ala-Arg-Val-Leu-Ala-Glu-Ala-Met-Ser, which covers a full binding epitope of capsid(CA)-p2, cleavage site. 2000 Journal of molecular biology Abstract HIV D25N 167 171 PR;PR;Capsid;Capsid 41;182;301;308 49;190;307;310 10969347 Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 107 112 10969347 Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 67 72 10969347 Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure. Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 58 63 10969347 Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure. We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 36 41 RT 76 78 10971861 Intensification of background antiretroviral therapy with abacavir during low-level failure may restore optimal suppression. The lamivudine resistance-associated mutation M184V was present in four of seven cases. 2000 Antiviral therapy Abstract HIV M184V 46 51 10978152 Molecular architecture of the mutagenic active site of human immunodeficiency virus type 1 reverse transcriptase: roles of the beta 8-alpha E loop in fidelity, processivity, and substrate interactions. Q151N RT showed enhanced ability to discriminate between TTP and AZT triphosphate, consistent with the observation that the Q151M mutation confers AZT resistance in vivo. 2000 Biochemistry Abstract HIV Q151M;Q151N 124;0 129;5 RT 6 8 10982378 Immunogenicity of mutations induced by nucleoside reverse transcriptase inhibitors for human immunodeficiency virus type 1-specific cytotoxic T cells. Two HIV-1(LAI) RT regions encompassing mutation M41L, L74V, M184V, and T215Y/F were recognized in 75 and 83% mutated and in 33 and 42% unmutated samples, respectively. 2000 Journal of virology Abstract HIV L74V;M184V;M41L;T215F;T215Y 54;60;48;71;71 58;65;52;78;78 RT 15 17 10983633 Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission. An evaluable sample was obtained from one of these three women 33 months after delivery; the K103N mutation was not detected in that sample. 2000 AIDS (London, England) Abstract HIV K103N 93 98 10983633 Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission. CONCLUSIONS: This preliminary study demonstrates that HIV-1 with the RT K103N mutation can be detected in some Ugandan women following a single dose of NVP. 2000 AIDS (London, England) Abstract HIV K103N 72 77 RT 69 71 10983633 Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission. RESULTS: The K103N NVP resistance mutation was detected 6 weeks after NVP administration in three (20%) out of 15 women (95% confidence interval, 0-40%). 2000 AIDS (London, England) Abstract HIV K103N 13 18 10983633 Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission. Women with the K103N mutation had a longer median NVP elimination half-life, decreased median oral clearance, and increased median area under the concentration time curve than those without the mutation. 2000 AIDS (London, England) Abstract HIV K103N 15 20 10996397 Effects of beta-L-3'-azido-3'-deoxythymidine 5'-triphosphate on host and viral DNA polymerases. Finally, L-AZTTP was found to lack affinity for the mutant RT at position 184 (M184V) demonstrating that this mutation confers resistance not only to beta-L-2',3'-dideoxycytidine analogs as previously reported by our group [Faraj et al., 1994. 2000 Antiviral research Abstract HIV M184V 79 84 RT 59 61 10998332 Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants. However, PR V82T was out-competed by WT. 2000 Virology Abstract HIV V82T 12 16 PR 9 11 10998332 Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants. PR M46I and L63P were as fit as WT. 2000 Virology Abstract HIV L63P;M46I 12;3 16;7 PR 0 2 10998332 Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants. The similar fitness of WT (NL4-3), L63P, and M46I is consistent with the common occurrence of L63P in the absence of protease inhibitor-selection pressure, but not with the rare detection of M46I in drug-naive patients. 2000 Virology Abstract HIV L63P;L63P;M46I;M46I 35;94;45;191 39;98;49;195 PR 117 125 10998332 Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants. Thus, the impaired fitness of the V82T single mutant is consistent with its low frequency in protease inhibitor-naive patients. 2000 Virology Abstract HIV V82T 34 38 PR 93 101 10998332 Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants. To examine the replicative fitness of HIV-1 mutants with single, drug-selected substitutions in protease (PR), we constructed virus that contained the most common mutations in indinavir-selected clinical isolates, PR M46I and V82T, and the most common polymorphic change in drug-naive patients, PR L63P. 2000 Virology Abstract HIV L63P;M46I;V82T 298;217;226 302;221;230 PR;PR;PR;PR 96;106;214;295 104;108;216;297 10999473 Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase. HI-511 R inhibited the HIV-strain A17 variant, containing RT mutations Y181C plus K103N, with an IC50 value of 2.7 microM, whereas the IC50 values of nevirapine, delavirdine, and trovirdine against this highly NNI-resistant HIV-1 strain were >100 microM. 2000 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 82;71 87;76 RT 58 60 10999473 Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase. When tested against the NNI-resistant HIV-1 strain A17 with a Y181C mutation in RT, HI-511R was found to be 10,000-times more active than nevirapine, 5000-times more active than delavirdine, and 50-times more active than trovirdine. 2000 Bioorganic & medicinal chemistry letters Abstract HIV Y181C 62 67 RT 80 82 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. Introduction of S68G in the RT of both the WT isolate and HIV-1(HXB2) partially restored replication capacity of recombinants carrying the 151L mutation. 2000 Journal of virology Abstract HIV S68G 16 20 RT 28 30 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. Only a small proportion of patients develop multiple dideoxynucleoside resistance (MDNR) mediated by the Q151M mutation. 2000 Journal of virology Abstract HIV Q151M 105 110 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. The 151L and 151K mutations were introduced by site-directed mutagenesis in RTs from two patient-derived HIV-1 isolates that had either wild type (WT) Q or the Q151M (posttreatment isolate) mutation. 2000 Journal of virology Abstract HIV Q151M 160 165 RT 76 79 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. The demonstrated ability of HIV-1(151L/68G) to replicate and the associated MDNR suggest that 151L is a potential intermediate of Q151M. 2000 Journal of virology Abstract HIV Q151M 130 135 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. The dependence of HIV-1(151L) on other mutations, such as S68G, for replication may explain the low frequency of the Q151M-mediated pathway of resistance. 2000 Journal of virology Abstract HIV Q151M;S68G 117;58 122;62 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. The majority of human immunodeficiency virus type 1 (HIV-1)-infected patients treated with zidovudine (AZT) plus zalcitabine (ddC) and didanosine (ddI) develop AZT resistance mediated by mutations such as T215Y and M41L. 2000 Journal of virology Abstract HIV M41L;T215Y 215;205 219;210 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. The S68G mutation alone did not confer a significant replicative disadvantage in WT viruses. 2000 Journal of virology Abstract HIV S68G 4 8 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. Three mutations (V35I, S68G, and I178M) were present in the RT background of the posttreatment isolate but not in the WT isolate. 2000 Journal of virology Abstract HIV I178M;S68G;V35I 33;23;17 38;27;21 RT 60 62 11000201 Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. To gain insight into the factors responsible for the low frequency of selection of Q151M, we evaluated the replication capabilities of recombinant viruses carrying two possible intermediates (151L or 151K) of the Q151M mutation generated in different reverse transcriptase (RT) genetic backgrounds. 2000 Journal of virology Abstract HIV Q151M;Q151M 83;213 88;218 RT;RT 251;274 272;276 11000223 3'-Azido-3'-deoxythymidine (AZT) and AZT-resistant reverse transcriptase can increase the in vivo mutation rate of human immunodeficiency virus type 1. It was observed that only high-level, AZT-resistant RT variants could influence the in vivo mutation rate (i.e., M41L/T215Y and M41L/D67N/K70R/T215Y). 2000 Journal of virology Abstract HIV D67N;K70R;M41L;T215Y;M41L;T215Y 133;138;128;143;113;118 137;142;132;148;117;123 RT 52 54 11000223 3'-Azido-3'-deoxythymidine (AZT) and AZT-resistant reverse transcriptase can increase the in vivo mutation rate of human immunodeficiency virus type 1. Replication of HIV-1 with AZT-resistant RTs increased the mutation rate by as much as a factor of 3, while replication of HIV-1 with a 3TC-resistant RT (M184V) had no significant effect on the mutation rate. 2000 Journal of virology Abstract HIV M184V 153 158 RT;RT 40;149 43;151 11000239 Comparison of second-strand transfer requirements and RNase H cleavages catalyzed by human immunodeficiency virus type 1 reverse transcriptase (RT) and E478Q RT. E478Q RT did cleave the truncated forms of the substrates, Delta6, Delta9, and Delta12, in a polymerase-independent assay. 2000 Journal of virology Abstract HIV E478Q 0 5 Pol;RT 93;6 103;8 11000239 Comparison of second-strand transfer requirements and RNase H cleavages catalyzed by human immunodeficiency virus type 1 reverse transcriptase (RT) and E478Q RT. However, when complemented with Escherichia coli RNase H, E478Q RT supported strand transfer with the truncated substrates. 2000 Journal of virology Abstract HIV E478Q 58 63 RT 64 66 11000239 Comparison of second-strand transfer requirements and RNase H cleavages catalyzed by human immunodeficiency virus type 1 reverse transcriptase (RT) and E478Q RT. In contrast, no RNase H activity was observed with the Delta6, Delta9, and Delta12 substrates with E478Q RT in this strand transfer assay. 2000 Journal of virology Abstract HIV E478Q 99 104 RT 105 107 11000239 Comparison of second-strand transfer requirements and RNase H cleavages catalyzed by human immunodeficiency virus type 1 reverse transcriptase (RT) and E478Q RT. The mutant RT, E478Q correctly catalyzed the initial cleavage of the 18-mer tRNA-DNA mimic in the presence of Mn(2+); however, no directional processing was observed. 2000 Journal of virology Abstract HIV E478Q 15 20 RT 11 13 11000239 Comparison of second-strand transfer requirements and RNase H cleavages catalyzed by human immunodeficiency virus type 1 reverse transcriptase (RT) and E478Q RT. The size requirements of the substrates which were cleaved by the polymerase-independent RNase H activity of E478Q RT are defined. 2000 Journal of virology Abstract HIV E478Q 109 114 Pol;RT 66;115 76;117 11008119 Structure-based drug design of non-nucleoside inhibitors for wild-type and drug-resistant HIV reverse transcriptase. Modeling studies revealed that for an NNI of HIV RT to be active against RT mutants such as the especially problematic Y181C RT mutant, the following features are required: (a) the inhibitor should be highly potent against wild-type RT and therefore capable of tolerating a considerable activity loss against RT mutants. 2000 Biochemical pharmacology Abstract HIV Y181C 119 124 RT;RT;RT;RT;RT 49;73;125;233;309 51;75;127;235;311 11009599 Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. Another contribution of the V82F/I84V to binding affinity originates from an increase in the energy penalty associated with the conformational change of the protease upon binding. 2000 Biochemistry Abstract HIV I84V;V82F 33;28 37;32 PR 157 165 11009599 Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. The active site mutant V82F/I84V has been shown to lower the binding affinity of protease inhibitors in clinical use. 2000 Biochemistry Abstract HIV I84V;V82F 28;23 32;27 PR 81 89 11009599 Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. The predominantly enthalpic effect of the V82F/I84V mutation is consistent with the idea that the introduction of the bulkier Phe side chain at position 82 and the Val side chain at position 84 distort the binding site and weaken van der Waals and other favorable interactions with inhibitors preshaped to the wild-type binding site. 2000 Biochemistry Abstract HIV I84V;V82F 47;42 51;46 11009599 Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. The V82F/I84V active site mutation lowers the affinity of the inhibitors by making the binding enthalpy more positive and making the entropy change slightly less favorable. 2000 Biochemistry Abstract HIV I84V;V82F 9;4 13;8 11009599 Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. The V82F/I84V mutant is structurally more stable than the wild-type protease by about 1.4 kcal/mol. 2000 Biochemistry Abstract HIV I84V;V82F 9;4 13;8 PR 68 76 11009599 Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant. To identify the origin of this effect, we have investigated the binding thermodynamics of the protease inhibitors indinavir, ritonavir, saquinavir, and nelfinavir to the wild-type HIV-1 protease and to the V82F/I84V resistant mutant. 2000 Biochemistry Abstract HIV I84V;V82F 211;206 215;210 PR;PR 94;186 102;194 11017792 Drug-resistant reverse transcriptase genotyping and phenotyping of B and non-B subtypes (F and A) of human immunodeficiency virus type I found in Brazilian patients failing HAART. A novel result was that some RT sequences not only revealed the presence of G333D/E mutations but also correlated to the presence of mutation T386I that could abrogate the M184V-surpassing effect of L210W or L210W plus G333D/E. 2000 Virology Abstract HIV G333D;G333D;G333E;G333E;L210W;L210W;M184V;T386I 76;219;76;219;199;208;172;142 83;226;83;226;204;213;177;147 RT 29 31 11018858 Natural residues versus antiretroviral drug-selected mutations in HIV type 1 group O reverse transcriptase and protease related to virological drug failure in vivo. While a multitude of mutations in HIV-1 group O reverse transcriptase (RT) and protease appeared that are associated with drug resistance in group M viruses, the observed T215N mutation in RT and the V15I and V22A mutations in protease have not previously been described and may represent resistance-conferring mutations specific to group O viruses. 2000 AIDS research and human retroviruses Abstract HIV T215N;V15I;V22A 171;200;209 176;204;213 RT;PR;PR;RT;RT 48;79;227;71;189 69;87;235;73;191 11018861 Mutations in the HIV type 1 integrase of patients receiving long-term dideoxynucleoside therapy do not confer resistance to zidovudine. Although most mutations occurred at nonconserved amino acids, one patient developed a mutation at codon (R166T), a residue that is conserved among all integrases from known HIV-1 isolates. 2000 AIDS research and human retroviruses Abstract HIV R166T 105 110 IN 151 161 11018861 Mutations in the HIV type 1 integrase of patients receiving long-term dideoxynucleoside therapy do not confer resistance to zidovudine. We show that the R166T integrase mutant is still proficient at carrying 3'-processing and 3' end-joining but that the enzyme is not resistant to AZT-TP. 2000 AIDS research and human retroviruses Abstract HIV R166T 17 22 IN 23 32 11036040 Delavirdine in combination with zidovudine in treatment of human immunodeficiency virus type 1-infected patients: evaluation of efficacy and emergence of viral resistance in a randomized, comparative phase III trial. The M/3331/0013B Study Group. The K103N mutation, which confers nonnucleoside reverse transcriptase inhibitor cross-resistance, was found in 85% of the patients. 2000 Antimicrobial agents and chemotherapy Abstract HIV K103N 4 9 NNRTI 34 69 11044115 Genotypic, phenotypic, and modeling studies of a deletion in the beta3-beta4 region of the human immunodeficiency virus type 1 reverse transcriptase gene that is associated with resistance to nucleoside reverse transcriptase inhibitors. The deletion was most frequently found in strains with the Q151M mutation. 2000 Journal of virology Abstract HIV Q151M 59 64 11045610 Systematic mutational analysis of the active-site threonine of HIV-1 proteinase: rethinking the "fireman's grip" hypothesis. PR(T26A), which lacks the "fireman's grip" interaction, was virtually inactive and was monomeric in solution at conditions where wild-type PR exhibited a monomer-dimer equilibrium. 2000 Protein science Abstract HIV T26A 3 7 PR;PR 0;139 2;141 11045610 Systematic mutational analysis of the active-site threonine of HIV-1 proteinase: rethinking the "fireman's grip" hypothesis. PR(T26S) and PR(T26C) showed similar or slightly reduced activity compared to wild-type HIV-1 PR, indicating that the sulfhydryl group of cysteine can substitute for the hydroxyl of the conserved threonine in this position. 2000 Protein science Abstract HIV T26C;T26S 16;3 20;7 PR;PR;PR 0;13;94 2;15;96 11054458 Role of Q190 of MuLV RT in ddNTP resistance and fidelity of DNA synthesis: a molecular model of interactions with substrates. However, the shorter side chain of Q190N (or A) mutant MuLV RT and the absence of 3'OH in ddNTP result in the rearrangement of hydrophobic interactions favoring the binding and limited incorporation of ddNTPs. 2000 Protein engineering Abstract HIV Q190N 35 40 RT 60 62 11054458 Role of Q190 of MuLV RT in ddNTP resistance and fidelity of DNA synthesis: a molecular model of interactions with substrates. We now report that both Q190N and Q190A MuLV RTs are more efficient in their activity to incorporate ddNTPs and exhibit higher fidelity than the wild-type (WT) enzyme of DNA synthesis in both RNA- and DNA-directed reactions. 2000 Protein engineering Abstract HIV Q190A;Q190N 34;24 39;29 RT 45 48 11060045 Genetic diversity of protease and reverse transcriptase sequences in non-subtype-B human immunodeficiency virus type 1 strains: evidence of many minor drug resistance mutations in treatment-naive patients. In order of decreasing frequency, the following mutations were identified in the protease gene: M36I (86.6%), L10I/V (26%), L63P (12.6%), K20M/R (11.2%), V77I (5.6%), A71V (2.8%), L33F (0.7%), and M46I (0.7%). 2000 Journal of clinical microbiology Abstract HIV A71V;K20M;K20R;L10I;L10V;L33F;L63P;M36I;M46I;V77I 167;138;138;110;110;180;124;96;197;154 171;144;144;116;116;184;128;100;201;158 PR 81 89 11060045 Genetic diversity of protease and reverse transcriptase sequences in non-subtype-B human immunodeficiency virus type 1 strains: evidence of many minor drug resistance mutations in treatment-naive patients. Major mutations linked to resistance to non-NRTI agents were detected in all group O isolates (A98G and Y181C) and in one subtype J virus (V108I). 2000 Journal of clinical microbiology Abstract HIV A98G;V108I;Y181C 95;139;104 100;144;109 NNRTI 40 48 11060045 Genetic diversity of protease and reverse transcriptase sequences in non-subtype-B human immunodeficiency virus type 1 strains: evidence of many minor drug resistance mutations in treatment-naive patients. R211K, an accessory mutation associated with NRTI resistance, was also observed in 43.6% of the samples. 2000 Journal of clinical microbiology Abstract HIV R211K 0 5 NRTI 45 49 11060499 Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. Incidence, association with other mutations, and effects on the structure of mutated reverse transcriptase. A mutation at codon 210 (mainly L210W) was found in 647 (32%) of the 2,049 sequences analyzed. 2000 Journal of biomedical science Abstract HIV L210W 32 37 11060499 Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. Incidence, association with other mutations, and effects on the structure of mutated reverse transcriptase. Follow-up studies demonstrated that L210W appeared always after T215Y/F. 2000 Journal of biomedical science Abstract HIV L210W;T215F;T215Y 36;64;64 41;71;71 11060499 Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. Incidence, association with other mutations, and effects on the structure of mutated reverse transcriptase. In contrast, 98% of these 647 sequences were also mutated at codon 215 (essentially T215Y/F), and 94% at codon 41 (mainly M41L). 2000 Journal of biomedical science Abstract HIV M41L;T215F;T215Y 122;84;84 126;91;91 11060499 Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. Incidence, association with other mutations, and effects on the structure of mutated reverse transcriptase. Mutation L210W of HIV-1 reverse transcriptase (RT) is one of the six main mutations that confer in vivo resistance to zidovudine. 2000 Journal of biomedical science Abstract HIV L210W 9 14 RT;RT 24;47 45;49 11060499 Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. Incidence, association with other mutations, and effects on the structure of mutated reverse transcriptase. The aim of this study was: (1) to study the frequency of mutation L210W in a large collection of HIV-1 sequences (2,049 samples, including 395 DNA and 1,654 RNA sequences) from patients receiving combination therapy, and (2) to analyze its association with the other mutations that confer resistance to zidovudine. 2000 Journal of biomedical science Abstract HIV L210W 66 71 11060499 Mutation L210W of HIV-1 reverse transcriptase in patients receiving combination therapy. Incidence, association with other mutations, and effects on the structure of mutated reverse transcriptase. These data showing a close association between L210W, T215Y/F, and M41L, and a mutual exclusion between K70R and L210W, were confirmed by analyzing the sequences stored in the HIV-1 sequences available through the Stanford HIV RT and Protease Database. 2000 Journal of biomedical science Abstract HIV K70R;L210W;L210W;M41L;T215F;T215Y 104;47;113;67;54;54 108;52;118;71;61;61 PR;RT 234;227 242;229 11064501 Comparison of immunologic restoration and virologic response in plasma, tonsillar tissue, and cerebrospinal fluid in HIV-1-infected patients treated with double versus triple antiretroviral therapy in very early stages: The Spanish EARTH-2 Study. Early Anti-Retroviral Therapy Study. After 1 year of therapy, 13 of 21 patients (62%) in the double-therapy groups (zidovudine plus lamivudine [n = 9] and stavudine plus lamivudine [n = 12]) had evidence of M184V mutation. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 170 175 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. A competitive fitness study failed to reveal any differences in replication rates between the delta 67+T69G/K70R/L74I/K103N/T215F/+ ++K219Q mutant and Wt. 2000 Journal of virology Abstract HIV T69G;K103N;K70R;L74I;T215F;K219Q 103;118;108;113;124;134 107;123;112;117;129;139 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. A high-level 3'-azido-3'-deoxythymidine (AZT)-resistant variant containing delta 67 plus T69G/K70R/L74I/K103N/T215F/K219Q in RT replicated as efficiently as wild-type virus (Wt). 2000 Journal of virology Abstract HIV K103N;K219Q;K70R;L74I;T215F;T69G 104;116;94;99;110;89 109;121;98;103;115;93 RT 125 127 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. Evaluation of proviral DNA sequences over a 3-year period in a patient harboring the multiresistant HIV revealed that the T69G mutation emerged in the context of a D67N/K70R/T215F/K219Q mutant backbone prior to appearance of the delta 67 deletion. 2000 Journal of virology Abstract HIV D67N;K219Q;K70R;T215F;T69G 164;180;169;174;122 168;185;173;179;126 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. Subsequently, the development of the delta 67 deletion led to a virus with improved replication and high-level AZT resistance. 2000 Journal of virology Abstract HIV delta 67 37 45 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. The combination of an amino acid deletion at codon 67 (delta 67) and Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is associated with high-level resistance to multiple RT inhibitors. 2000 Journal of virology Abstract HIV delta 67;T69G;T69G 55;100;69 63;104;98 RT;RT;RT 113;136;240 134;138;242 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. The T69G mutation was found to confer 2',3'-dideoxyinosine resistance at the expense of fitness. 2000 Journal of virology Abstract HIV T69G 4 8 11069990 Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69. To determine the relative contributions of the delta 67 and T69G mutations on viral fitness, we performed a series of studies of HIV replication using recombinant variants. 2000 Journal of virology Abstract HIV T69G 60 64 11080630 Structural basis for the resilience of efavirenz (DMP-266) to drug resistance mutations in HIV-1 reverse transcriptase. In order to understand the basis for this resilience at the molecular level and to help the design of further-improved anti-AIDS drugs, we have determined crystal structures of efavirenz and nevirapine with wild-type RT and the clinically important K103N mutant. 2000 Structure (London, England Abstract HIV K103N 249 254 RT 217 219 AIDS 124 128 11083661 Differential removal of thymidine nucleotide analogues from blocked DNA chains by human immunodeficiency virus reverse transcriptase in the presence of physiological concentrations of 2'-deoxynucleoside triphosphates. ATP-dependent removal of either d4TMP or 3'-azido-3'-deoxythymidine-5'-monophosphate (AZTMP) is increased in AZT resistant HIV-1 RT (containing D67N/K70R/T215F/K219Q mutations). 2000 Antimicrobial agents and chemotherapy Abstract HIV D67N;K219Q;K70R;T215F 144;160;149;154 148;165;153;159 RT 129 131 11087358 Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr. A single point mutation of the Pro at residue 333 to a Glu totally abolishes the binding of HIV-1 Vpr to UBA(2). 2000 Biochemistry Abstract HIV P333E 31 58 Vpr 98 101 11087358 Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr. High resolution NMR structures of the binding deficient UBA(2) mutant P333E as well as of the wild-type UBA(2) domain were determined to compare the effect of this mutation on the structure. 2000 Biochemistry Abstract HIV P333E 70 75 11090748 A genotypic analysis of patients receiving Zidovudine with either Lamivudine, Didanosine or Zalcitabine dual therapy using the LiPA point mutation assay to detect genotypic variation at codons 41, 69, 70, 74, 184 and 215. RESULTS: The M184V mutation was observed in 47.0% of patients receiving ZDV+3TC combination therapy but was not observed in either patient group receiving either ddI or ddC as co-therapy with ZDV. 2000 Journal of clinical virology Abstract HIV M184V 13 18 11090748 A genotypic analysis of patients receiving Zidovudine with either Lamivudine, Didanosine or Zalcitabine dual therapy using the LiPA point mutation assay to detect genotypic variation at codons 41, 69, 70, 74, 184 and 215. The M184V mutation of the reverse transcriptase gene of HIV-1 has been associated with resistance to 3TC, ddC and ddI. 2000 Journal of clinical virology Abstract HIV M184V 4 9 RT 26 47 11090748 A genotypic analysis of patients receiving Zidovudine with either Lamivudine, Didanosine or Zalcitabine dual therapy using the LiPA point mutation assay to detect genotypic variation at codons 41, 69, 70, 74, 184 and 215. There was no evidence of the L74V mutation in our study group in either the ZDV/ddI or ZDV/ddC combination therapy group. 2000 Journal of clinical virology Abstract HIV L74V 29 33 11090748 A genotypic analysis of patients receiving Zidovudine with either Lamivudine, Didanosine or Zalcitabine dual therapy using the LiPA point mutation assay to detect genotypic variation at codons 41, 69, 70, 74, 184 and 215. We found the frequency of the K70R mutation to be higher in patients treated with ZDV/ddI (P=0.033) or ZDV/ddC (P=0.3) when compared with patients treated with ZDV/3TC. 2000 Journal of clinical virology Abstract HIV K70R 30 34 11093845 [Prevalence of primary mutations in human immunodeficiency virus with resistance to nucleoside analogues in previously untreated patients from Andalusia. Andalusian Group for the Study of Infectious diseases (GAEI)]. PATIENTS AND METHOD: Genotype study (LiPA) of mutations in codons M41L, T69D, K70R, L74V, M184V, T215Y/F and RT75G-S was performed in 106 HIV-naive patients from 12 Andalusian hospitals, with viral load over 5000 copies of RNA/ml. 2000 Medicina clinica Abstract HIV K70R;L74V;M184V;M41L;T215F;T215Y;T69D 78;84;90;66;97;97;72 82;88;95;70;104;104;76 RT 109 111 11101143 Characterization of mutant HIV-1 integrase carrying amino acid changes in the catalytic domain. Change of E152V in the DD(35)E motif abolished all detectable activities of IN. 2000 Molecules and cells Abstract HIV E152V 10 15 IN 76 78 11101143 Characterization of mutant HIV-1 integrase carrying amino acid changes in the catalytic domain. Mutant P90D weakly reduced the 3'-processing but severely affected the two other IN activities. 2000 Molecules and cells Abstract HIV P90D 7 11 IN 81 83 11101143 Characterization of mutant HIV-1 integrase carrying amino acid changes in the catalytic domain. Results obtained from double and triple mutations, P90D/P1451 and P145I/F185K/C280S, clearly suggest a crucial role of P145 in the catalytic function of IN, whereas the mutants V150E, L158F and L172M had no detectable effect on any of the IN activities. 2000 Molecules and cells Abstract HIV C280S;F185K;P145I;L158F;L172M;P90D;P90P;V150E 78;72;66;184;194;51;51;177 83;77;71;189;199;55;55;182 IN;IN 153;239 155;241 11106162 Crystal structure of an in vivo HIV-1 protease mutant in complex with saquinavir: insights into the mechanisms of drug resistance. Three HIV-1 protease mutant species, G48V, L90M, and G48V/L90M double mutant, are associated in vivo with saquinavir resistance by the enzyme (Jacobsen et al., 1996). 2000 Protein science Abstract HIV G48V;G48V;L90M;L90M 37;53;58;43 41;57;62;47 PR 12 20 11106162 Crystal structure of an in vivo HIV-1 protease mutant in complex with saquinavir: insights into the mechanisms of drug resistance. To gain an understanding of how these mutations modulate inhibitor binding, we have solved the HIV-1 protease crystal structure of the G48V/L90M double mutant in complex with saquinavir at 2.6 A resolution. 2000 Protein science Abstract HIV G48V;L90M 135;140 139;144 PR 101 109 11114828 Altered viral fitness of HIV-1 following failure of protease inhibitor-based therapy. One additional posttreatment isolate with the M184V mutation in reverse transcriptase showed diminished replication. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 46 51 RT 64 85 11114828 Altered viral fitness of HIV-1 following failure of protease inhibitor-based therapy. Two of five post-treatment isolates exhibited decreased replication in hu-PBL-SCID mice compared with the paired pretreatment isolate, and both had the V82A mutation in protease associated with resistance to PI. 2000 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V82A 152 156 PR;PI 169;208 177;210 11118853 Resistance to antiretroviral drugs in patients with primary HIV-1 infection. Investigators of the Quebec Primary Infection Study. The prevalence of mutations that conferred primary resistance to PIs (L10I, D30Y, V82A, L90M) was 15% of the cohort. 2000 International journal of antimicrobial agents Abstract HIV D30Y;L10I;L90M;V82A 76;70;88;82 80;74;92;86 PI 65 68 11120945 Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564. On the contrary, the gp41 mutation (R533A) did not appear to affect the IC9564 sensitivity. 2001 Antimicrobial agents and chemotherapy Abstract HIV R533A 36 41 gp41 21 25 11120945 Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564. The mutations are G237R and R252K in gp120 and R533A in the fusion domain of gp41. 2001 Antimicrobial agents and chemotherapy Abstract HIV G237R;R252K;R533A 18;28;47 23;33;52 gp120;gp41 37;77 42;81 11120956 Molecular modeling approach to understanding the mode of action of L-nucleosides as antiviral agents. Additionally, the clinically important M184V mutation, which confers resistance against 3TC and FTC, was studied with our modeling system. 2001 Antimicrobial agents and chemotherapy Abstract HIV M184V 39 44 11120956 Molecular modeling approach to understanding the mode of action of L-nucleosides as antiviral agents. The binding energy patterns of nucleoside inhibitors at the M184V mutation site correlate with the reported antiviral data. 2001 Antimicrobial agents and chemotherapy Abstract HIV M184V 60 65 11124910 Substitution of Asp114 or Arg116 in the fingers domain of moloney murine leukemia virus reverse transcriptase affects interactions with the template-primer resulting in decreased processivity. D114A and R116A enzymes also bind more weakly to template-primer in the presence of added deoxyribonucleotides, as seen by gel-shift analysis, but retain the ability to strand transfer and accumulate smaller RNase H cleavage products when compared to the wild-type enzyme. 2001 Journal of molecular biology Abstract HIV R116A;D114A 10;0 15;5 11124910 Substitution of Asp114 or Arg116 in the fingers domain of moloney murine leukemia virus reverse transcriptase affects interactions with the template-primer resulting in decreased processivity. In addition, mutant proviruses, including D114A and R116A substitutions in Moloney murine leukemia virus reverse transcriptase, are not viable despite the presence of processed reverse transcriptase in the viral particles. 2001 Journal of molecular biology Abstract HIV D114A;R116A 42;52 47;57 RT;RT 105;177 126;198 11124910 Substitution of Asp114 or Arg116 in the fingers domain of moloney murine leukemia virus reverse transcriptase affects interactions with the template-primer resulting in decreased processivity. Substitution of Ala for either Asp114 or Arg116, two highly conserved residues in the fingers domain of Moloney murine leukemia virus reverse transcriptase, results in enzymes (D114A or R116A) with significant defects in their abilities to processively synthesize DNA using RNA or DNA as a template. 2001 Journal of molecular biology Abstract HIV D114A;R116A 177;186 183;191 RT;Asp 134;31 155;34 11134027 The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. In addition, V75T increases the DNA polymerization rate up to 5-fold by facilitating translocation along nucleic acid single-stranded templates. 2001 The Journal of biological chemistry Abstract HIV V75T 13 17 11134027 The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. The amino acid change V75T in human immunodeficiency virus type 1 reverse transcriptase confers a low level of 2',3'-didehydro-2',3'-dideoxythymidine (stavudine, d4T) resistance in vivo and in vitro. 2001 The Journal of biological chemistry Abstract HIV V75T 22 26 RT 66 87 11134027 The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. The V75T/Y146F double substitution partially suppressed both increases in rate of polymerization and pyrophosphorolysis, indicating that the hydroxyl group of Thr-75 interacts with that of Tyr-146. 2001 The Journal of biological chemistry Abstract HIV V75T;Y146F 4;9 8;14 11134027 The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. Thus, in addition to nucleotide selectivity V75T defines a type of amino acid change conferring resistance to nucleoside analogues that links translocation rate to the traffic of pyrophosphate at the reverse transcriptase active site. 2001 The Journal of biological chemistry Abstract HIV V75T 44 48 RT 200 221 11134027 The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. V75T also increases the reverse transcriptase-mediated repair of the d4TMP-terminated DNA by pyrophosphate but not by ATP. 2001 The Journal of biological chemistry Abstract HIV V75T 0 4 RT 24 45 11134027 The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. V75T recombinant virus was 3-4-fold d4T-resistant and 3-fold resistant to phosphonoformic acid relative to wild type, confirming that the pyrophosphate traffic is affected in V75T reverse transcriptase. 2001 The Journal of biological chemistry Abstract HIV V75T;V75T 175;0 179;4 RT 180 201 11134027 The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. V75T reverse transcriptase discriminates 3.6-fold d4T 5'-triphosphate relative to dTTP, as judged by pre-steady state kinetics of incorporation of a single nucleotide into DNA. 2001 The Journal of biological chemistry Abstract HIV V75T 0 4 RT 5 26 11142631 Piperidinylethyl, phenoxyethyl and fluoroethyl bromopyridyl thiourea compounds with potent anti-HIV activity. Notably, the lead fluorothiourea compounds 11 and 12 were both substantially more active against the NNRTI-resistant HIV strains RT-MDR (V106A) and A17 (Y181C) than nevirapine or delavirdine. 2000 Antiviral chemistry & chemotherapy Abstract HIV V106A;Y181C 137;153 142;158 NNRTI;RT 101;129 106;131 11152134 Trp42 rotamers report reduced flexibility when the inhibitor acetyl-pepstatin is bound to HIV-1 protease. The Q7K/L331/L631 HIV-1 protease mutant was expressed in Escherichia coli and the effect of binding a substrate-analog inhibitor, acetyl-pepstatin, was investigated by fluorescence spectroscopy and molecular dynamics. 2000 Protein science Abstract HIV Q7K 4 7 PR 24 32 11155314 Three-dimensional quantitative structure-activity relationships study on HIV-1 reverse transcriptase inhibitors in the class of dipyridodiazepinone derivatives, using comparative molecular field analysis. A three-dimensional quantitative structure-activity relationships (3D QSAR) method, Comparative Molecular Field Analysis (CoMFA), was applied to a set of dipyridodiazepinone (nevirapine) derivatives active against wild-type (WT) and mutant-type (Y181C) HIV-1 reverse transcriptase. 2000 Journal of molecular graphics & modelling Abstract HIV Y181C 246 251 RT 259 280 11155314 Three-dimensional quantitative structure-activity relationships study on HIV-1 reverse transcriptase inhibitors in the class of dipyridodiazepinone derivatives, using comparative molecular field analysis. CoMFA contour maps reveal that steric and electrostatic interactions corresponding to the WT inhibition amount to 58.5% and 41.5%, respectively, while steric and electrostatic effects have approximately equal contributions for the explanation of inhibitory activities against Y181C. 2000 Journal of molecular graphics & modelling Abstract HIV Y181C 276 281 11155314 Three-dimensional quantitative structure-activity relationships study on HIV-1 reverse transcriptase inhibitors in the class of dipyridodiazepinone derivatives, using comparative molecular field analysis. CoMFA was used to discriminate between structural requirements for WT and Y181C inhibitory activities. 2000 Journal of molecular graphics & modelling Abstract HIV Y181C 74 79 11155314 Three-dimensional quantitative structure-activity relationships study on HIV-1 reverse transcriptase inhibitors in the class of dipyridodiazepinone derivatives, using comparative molecular field analysis. The resulting CoMFA models yield satisfactory predictive ability regarding WT and Y181C inhibitions, with r2 cv = 0.624 and 0.726, respectively. 2000 Journal of molecular graphics & modelling Abstract HIV Y181C 82 87 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. 2001 The Journal of experimental medicine Abstract HIV R264G 22 27 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. 2001 The Journal of experimental medicine Abstract HIV L268M;R264K 50;14 93;19 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. 2001 The Journal of experimental medicine Abstract HIV E260D 37 91 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. 2001 The Journal of experimental medicine Abstract HIV R264G;R264K 95;85 100;91 Gag 68 71 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. We have detected a R264K mutation in four patients carrying HLA-B27. 2001 The Journal of experimental medicine Abstract HIV R264K 19 24 11158089 Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy. LiPA detected earlier and more frequently than sequencing the transient mixed virus population that contained I84V, which appears before V82A in the protease sequence. 2001 Journal of clinical microbiology Abstract HIV I84V;V82A 110;137 114;141 PR 149 157 11158089 Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy. Mutation I84V appears in minor populations in the early steps of the pathways of resistance to indinavir and ritonavir. 2001 Journal of clinical microbiology Abstract HIV I84V 9 13 11158089 Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy. Mutations M461, G48V, and L90M were often transient and drug pressure related. 2001 Journal of clinical microbiology Abstract HIV G48V;L90M 16;26 20;30 11160665 Genetic and functional diversity of human immunodeficiency virus type 1 subtype B Nef primary isolates. Mutations A29V and F193I were deleterious to CD4 downregulation and PAK-2 activation, respectively, while S189R rendered Nef defective for both MHC class I downregulation and PAK-2 activation. 2001 Journal of virology Abstract HIV A29V;F193I;S189R 10;19;106 14;24;111 Nef 121 124 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. In contrast, the Glu138Phe and Glu138Tyr RT mutants showed poor RNA-dependent DNA polymerase activity (30 and 4% of wild-type, respectively). 2001 Virology Abstract HIV E138F;E138Y 17;31 26;40 Pol;RT 82;41 92;43 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. Mixtures of Glu138Lys RT mutant virus with the other virus clones mutated at the 138 position resulted in all cases, except for the Glu138Asp and Glu138Gly RT mutant viruses, in an outgrowth of the Glu138Lys RT mutant virus. 2001 Virology Abstract HIV E138D;E138G;E138K;E138K 132;146;12;198 141;155;21;207 RT;RT;RT 22;156;208 24;158;210 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. Since the Glu138Lys RT proved most resistant to TSAO derivatives, was among the most catalytically efficient enzymes, and resulted in highly replication-competent virus, our data explain why the Glu138Lys RT mutant virus strains but not virus strains containing other amino acids at position 138 invariably emerge in cell cultures under TSAO drug pressure. 2001 Virology Abstract HIV E138K;E138K 10;195 19;204 RT;RT 20;205 22;207 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. The Glu138Asp RT mutant virus kept full sensitivity to the TSAO derivatives. 2001 Virology Abstract HIV E138D 4 13 RT 14 16 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. The Glu138Lys RT mutant virus had the most marked resistance to TSAOs, followed by the Glu138Gln, Glu138Phe, Glu138Gly, Glu138Tyr, and Glu138Ala virus mutants. 2001 Virology Abstract HIV E138A;E138F;E138G;E138K;E138Q;E138Y 135;98;109;4;87;120 144;107;118;13;96;129 RT 14 16 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. The mutant Glu138Asp, Glu138Lys, Glu138Gln, Glu138Ala, and Glu138Gly RTs retained marked catalytic activity. 2001 Virology Abstract HIV E138A;E138D;E138G;E138K;E138Q 44;11;59;22;33 53;20;68;31;42 RT 69 72 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. TSAO derivatives lost their inhibitory activity against all mutant enzymes, except against the closely related Glu138Asp RT mutant that remained as sensitive to TSAOs as did wild-type RT. 2001 Virology Abstract HIV E138D 111 120 RT;RT 121;184 123;186 11162823 Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138. TSAO derivatives represent a class of nonnucleoside reverse transcriptase inhibitors (NNRTIs) that consistently select for the Glu138Lys resistance mutation in HIV-1 reverse transcriptase (RT). 2001 Virology Abstract HIV E138K 127 136 NNRTI;RT;NNRTI;RT 38;166;86;189 73;187;92;191 11168414 Mapping DNA-binding sites of HIV-1 integrase by protein footprinting. A protein footprinting approach was employed to investigate the accessibility of residues in the full-length soluble integrase mutant, INF(185K,C280S), to proteolytic attack in the absence and presence of DNA. 2001 European journal of biochemistry Abstract HIV C280S 144 149 IN 117 126 11170214 1.9 A x-ray study shows closed flap conformation in crystals of tethered HIV-1 PR. Three-dimensional structure of an asymmetrically mutated (C95M) tethered human immunodeficiency virus type 1 protease enzyme (HIV-1 PR) has been determined in an unliganded form using X-ray diffraction data to 1.9 A resolution. 2001 Proteins Abstract HIV C95M 58 62 PR;PR 109;132 117;134 11170234 Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy. The most frequent RT mutations were T215Y/F, M41L, and M184V (41.9, 40.8, and 40.8%, respectively), while L63P, L10R/V, and A71V/T (58, 41.9, and 34.4%, respectively) were the most represented protease substitutions. 2001 Journal of clinical laboratory analysis Abstract HIV A71T;A71V;L10R;L10V;L63P;M184V;M41L;T215F;T215Y 124;124;112;112;106;55;45;36;36 130;130;118;118;110;60;49;43;43 PR;RT 193;18 201;20 11170234 Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy. We have found no mutations encoding for multiple dideoxynucleoside resistance (Q151M or T69SS). 2001 Journal of clinical laboratory analysis Abstract HIV Q151M;T69S 79;88 85;93 11170624 Estimation of binding affinities for HEPT and nevirapine analogues with HIV-1 reverse transcriptase via Monte Carlo simulations. A key pi-type hydrogen bond has been identified between secondary-amide nevirapine analogues and Tyr188A of HIVRT that explains their otherwise surprising activity and the ineffectiveness of nevirapine against the Y188C mutant. 2001 Journal of medicinal chemistry Abstract HIV Y188C 214 219 PI 6 8 11170982 Twice-daily triple nucleoside intensification treatment with lamivudine-zidovudine plus abacavir sustains suppression of human immunodeficiency virus type 1: results of the TARGET Study. Previous zidovudine or lamivudine use and presence at baseline of the M184V reverse-transcriptase mutation did not impact virologic response. 2001 The Journal of infectious diseases Abstract HIV M184V 70 75 RT 76 97 11176267 Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy. Multidrug-resistant mutation patterns including Q151M and insertion mutations at codon 69, which confer cross-resistance to the different nucleoside analogue RT inhibitors were detected in 1 and 3 patients, respectively; 1 patient with insertion mutation displayed a NGQGV [corrected] sequence at codons 67 to 70. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 48 53 RT 158 160 11177388 Efficacy, tolerance, and pharmacokinetics of the combination of stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or indinavir failure. At baseline, the mean number of mutations in the protease gene was 10 (2-19), and the V82A and L90M mutations were present in 54 and 21% of patients. 2001 AIDS research and human retroviruses Abstract HIV L90M;V82A 95;86 99;90 PR 49 57 11177388 Efficacy, tolerance, and pharmacokinetics of the combination of stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or indinavir failure. The presence of the V82A mutation did not affect significantly the rate of response (36 vs. 38%), whereas the L90M mutation was associated with treatment failure (0 vs. 43%). 2001 AIDS research and human retroviruses Abstract HIV L90M;V82A 110;20 114;24 11177403 Phenotypic cross-resistance to nelfinavir: the role of prior antiretroviral therapy and the number of mutations in the protease gene. Phenotypic resistance to NFV was associated with the presence of the L90M mutation: 46% for resistant vs. 2001 AIDS research and human retroviruses Abstract HIV L90M 69 73 11177403 Phenotypic cross-resistance to nelfinavir: the role of prior antiretroviral therapy and the number of mutations in the protease gene. The D30N mutation was detected in only 1 of 74 patients who failed. 2001 AIDS research and human retroviruses Abstract HIV D30N 4 8 11177403 Phenotypic cross-resistance to nelfinavir: the role of prior antiretroviral therapy and the number of mutations in the protease gene. The L90M mutation is significantly associated with the subsequent failure of NFV-containing regimens. 2001 AIDS research and human retroviruses Abstract HIV L90M 4 8 11177403 Phenotypic cross-resistance to nelfinavir: the role of prior antiretroviral therapy and the number of mutations in the protease gene. The presence of the D30N mutation was rare and not useful in identifying NFV-resistant isolates. 2001 AIDS research and human retroviruses Abstract HIV D30N 20 24 11177411 Genetic analysis of hiv type 1 strains in bujumbura (burundi): predominance of subtype c variant. However, mutation M36I, associated with resistance to ritonavir and nelfinavir, was found in 17 of 18 Burundi isolates. 2001 AIDS research and human retroviruses Abstract HIV M36I 18 22 11181376 Variant human immunodeficiency virus type 1 proteases and response to combination therapy including a protease inhibitor. A relatively poorer response to therapy was associated with a high number of baseline polymorphisms and, to a lesser extent, with the presence of I93L at baseline in comparison with the wild-type virus. 2001 Antimicrobial agents and chemotherapy Abstract HIV I93L 146 150 11181376 Variant human immunodeficiency virus type 1 proteases and response to combination therapy including a protease inhibitor. A71V/T was slightly associated with a poorer response to first-line ritonavir-based therapy. 2001 Antimicrobial agents and chemotherapy Abstract HIV A71T;A71V 0;0 6;6 11181376 Variant human immunodeficiency virus type 1 proteases and response to combination therapy including a protease inhibitor. I93L, occurring in about 30% of untreated patients, may play a role, as A71V/T possibly does in ritonavir-treated patients. 2001 Antimicrobial agents and chemotherapy Abstract HIV A71T;A71V;I93L 72;72;0 78;78;4 11181387 Prevalence and conditions of selection of E44D/A and V118I human immunodeficiency virus type 1 reverse transcriptase mutations in clinical practice. Recently, it has been shown that a new mutational pattern (the E44D/A and/or V118I mutation) confers moderate phenotypic lamivudine resistance in the absence of the M184V mutation. 2001 Antimicrobial agents and chemotherapy Abstract HIV E44A;E44D;M184V;V118I 63;63;165;77 69;69;170;82 11181387 Prevalence and conditions of selection of E44D/A and V118I human immunodeficiency virus type 1 reverse transcriptase mutations in clinical practice. The E44D/A and/or the V118I mutation does not exist in drug-naive patients, and the prevalence increases with the number of treatment regimens and lamivudine experience. 2001 Antimicrobial agents and chemotherapy Abstract HIV E44A;E44D;V118I 4;4;22 10;10;27 11181387 Prevalence and conditions of selection of E44D/A and V118I human immunodeficiency virus type 1 reverse transcriptase mutations in clinical practice. These mutations are more stable than the M184V substitution during antiretroviral treatment interruptions. 2001 Antimicrobial agents and chemotherapy Abstract HIV M184V 41 46 11181387 Prevalence and conditions of selection of E44D/A and V118I human immunodeficiency virus type 1 reverse transcriptase mutations in clinical practice. They are always associated with zidovudine resistance-associated mutations, even in the absence of M184V. 2001 Antimicrobial agents and chemotherapy Abstract HIV M184V 99 104 11205100 Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors. These amino acids are highly conserved in HIV-1, HIV-2, SIVmac and SIVagm, and the M184I (M185I in SIVagm) substitution was observed in 3TC-resistant HIV-1 and SIVmac. 2000 Archives of virology Abstract HIV M184I;M185I 83;90 88;96 11205100 Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors. Viruses resistant to delavirdine contained V112I and M231I substitutions, while those resistant to 3TC contained a M 185I substitution. 2000 Archives of virology Abstract HIV M185I;M231I;V112I 115;53;43 121;58;48 11206075 Ab initio molecular dynamics studies on HIV-1 reverse transcriptase triphosphate binding site: implications for nucleoside-analog drug resistance. Absence of this interaction in Lys65-->Arg HIV-1 RT might play a prominent role in the resistance of this mutant for nucleoside analogs (Gu Z et al., 1994b, Antimicrob Agents Chemother 38:275-281; Zhang D et al., 1994, Antimicrob Agents Chemother 38:282-287). 2000 Protein science Abstract HIV K65R 31 42 RT 49 51 11206075 Ab initio molecular dynamics studies on HIV-1 reverse transcriptase triphosphate binding site: implications for nucleoside-analog drug resistance. Absence of this stabilizing interaction in Gln151-->Met HIV-1 RT mutant may be a key factor for the known drug resistance of this mutant toward dideoxy-type drugs and AZT (Shirasaka T et al., 1995, Proc Natl Acad Sci USA 92:2398-2402: Iversen AK et al., 1996, J Virol 70:1086-1090). 2000 Protein science Abstract HIV Q151M 43 55 RT 62 64 11206461 3,3a-Dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones are potent non-nucleoside reverse transcriptase inhibitors. One of these compounds, as the racemate, possessed an IC90 = 4.6 nM against wild-type virus in a whole cell antiviral assay and had an IC90 = 76 and 897 nM against the clinically significant K103N and K103N/L100I mutant viruses, respectively. 2001 Bioorganic & medicinal chemistry letters Abstract HIV K103N;K103N;L100I 191;201;207 196;206;212 11227993 Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC. A substitution of methionine to valine was identified at position 184 (M184V) in variants selected with (+/-)dOTC. 2000 Antiviral chemistry & chemotherapy Abstract HIV M184V 71 76 11227993 Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC. In contrast, a mutation of lysine to arginine at position 65 (K65R) was found in variants selected with (+/-)dOTFC. 2000 Antiviral chemistry & chemotherapy Abstract HIV K65R;K65R 62;27 66;60 11227993 Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC. Studies with mutated recombinant HXB2D-M184V and -K65R confirmed that these mutations are important for phenotypic resistance in MT-2 cells. 2000 Antiviral chemistry & chemotherapy Abstract HIV K65R;M184V 50;39 54;44 11230439 In vitro evolution of the human immunodeficiency virus type 1 gag-protease region and maintenance of reverse transcriptase resistance following prolonged drug exposure. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. 2001 Journal of clinical microbiology Abstract HIV M46I 142 146 PR;Gag 99;95 107;98 11230439 In vitro evolution of the human immunodeficiency virus type 1 gag-protease region and maintenance of reverse transcriptase resistance following prolonged drug exposure. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. 2001 Journal of clinical microbiology Abstract HIV M46I;V82F 112;121 116;125 PR 80 88 11233298 [Pharmacological study and clinical effect of HIV protease inhibitor amprenavir]. One of the major concerns associated with anti-HIV agents is the resistance mutation development, and the presence of I50V, M46I/L, I47V, I54L/V and I84V genotype has been observed in amprenavir therapy experienced subjects. 2001 Nihon yakurigaku zasshi. Folia pharmacologica Japonica Abstract HIV I47V;I50V;I54L;I54V;I84V;M46I;M46L 132;118;138;138;149;124;124 136;122;144;144;153;130;130 11242181 Primary genotypic and phenotypic HIV-1 drug resistance in recent seroconverters in Madrid. A median infectious dose (IC50) increase of fourfold for any drug was found in 7 patients, and in 2 was > tenfold for zidovudine (genotype M41L + T215Y) and lamivudine (genotype M184V), respectively. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;M41L;T215Y 178;139;146 183;143;151 11242181 Primary genotypic and phenotypic HIV-1 drug resistance in recent seroconverters in Madrid. Zidovudine-resistance mutations M41L and/or T215Y were the commonest, found in 20% (6 of 30 participants). 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M41L;T215Y 32;44 36;49 11257034 Potentiation of inhibition of wild-type and mutant human immunodeficiency virus type 1 reverse transcriptases by combinations of nonnucleoside inhibitors and d- and L-(beta)-dideoxynucleoside triphosphate analogs. In this study, different combinations of nucleoside and nonnucleoside inhibitors, including D- and L-(beta)-deoxy- and -dideoxynucleoside triphosphate analogues, have been tested in in vitro RT assays against either recombinant wild-type RT or RT bearing clinically relevant nonnucleoside inhibitor resistance mutations (L100I, K103N, Y181I), and the nature of the interaction (either synergistic or antagonistic) of these associations was evaluated. 2001 Antimicrobial agents and chemotherapy Abstract HIV K103N;L100I;Y181I 328;321;335 333;326;340 RT;RT;RT 191;238;244 193;240;246 11264389 Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. Our results suggest that the Delta67 and T69G changes can be categorized as mutations associated with multidrug resistance. 2001 Journal of virology Abstract HIV T69G 41 45 11264389 Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. The combination of both mutations with an L74I change (Delta67+T69G/L74I) leads to a novel 3'-azido-3'-deoxythymidine resistance motif and compensates for impaired HIV replication. 2001 Journal of virology Abstract HIV T69G;L74I;L74I 63;68;42 67;72;46 11264389 Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. The potential roles of an amino acid deletion at codon 67 (Delta67) and a Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase of human immunodeficiency virus (HIV) type 1 in drug sensitivity and relative replication fitness were studied. 2001 Journal of virology Abstract HIV T69G;T69G 105;74 109;103 RT 118 139 11264998 International perspectives on antiretroviral resistance. Nucleoside reverse transcriptase inhibitor resistance. Other features of NRTI resistance, such as the theoretic reversal of zidovudine resistance associated with the M184V mutation or the powerful influence of the Q151M multiple-drug resistance mutation, have revealed the unpredictable nature of HIV resistance and how much we still need to learn. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;Q151M 111;159 116;164 NRTI 18 22 11266210 Different effects of a single amino acid substitution on three adjacent epitopes in the gp41 C-terminal tail of a neutralizing antibody escape mutant of human immunodeficiency virus type 1. Here we show that escape mutants selected with neutralizing ERDRD-specific antibody had a single 732R-->G substitution, 14 residues upstream of the cognate epitope, and no longer bound the selecting antibody. 2001 Archives of virology Abstract HIV R732G 97 105 11266210 Different effects of a single amino acid substitution on three adjacent epitopes in the gp41 C-terminal tail of a neutralizing antibody escape mutant of human immunodeficiency virus type 1. Introduction of 732R-->G by site-specific mutagenesis into the gp41 of cloned HIV-1 NL4-3 virions allowed them to escape neutralization by ERDRD-specific IgG, and confirms that 732R makes a major contribution to the neutralizing conformation of the 731-752 region of the C-terminal tail of gp41. 2001 Archives of virology Abstract HIV R732G 16 24 gp41;gp41 63;290 67;294 11300789 The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. Studies with this substrate labeled at the RNA 3' end showed that Y181C is no more likely than wild type to cleave toward the RNA 3' end. 2001 Biochemistry Abstract HIV Y181C 66 71 11300789 The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. Thus, Y181C RT has a strong preference to cleave in the direction of the RNA 5' end even when secondary cleavage is prevented, resulting in a disruption of the normal sequence of primary followed by secondary cleavages. 2001 Biochemistry Abstract HIV Y181C 6 11 RT 12 14 11300789 The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. Under these conditions, Y181C cleaved closer to the RNA 5' end than wild type. 2001 Biochemistry Abstract HIV Y181C 24 29 11300789 The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. We investigated the effects of the nonnucleoside reverse transcriptase inhibitor-resistant mutant Y181C on RNA 5'-end-directed RNase H cleavage by HIV-1 reverse transcriptase, using an RNA.DNA hybrid in which a radiolabeled RNA 5' end was recessed. 2001 Biochemistry Abstract HIV Y181C 98 103 NNRTI;RT 35;153 70;174 11300789 The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. When the RNA was 3'-end-labeled, Y181C generated a long product, which results when secondary cleavage precedes the primary. 2001 Biochemistry Abstract HIV Y181C 33 38 11300789 The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors alters the size distribution of RNase H cleavages. Y181C produced a higher ratio of secondary (9 nucleotide long) to primary (18 nucleotide long) products than wild type. 2001 Biochemistry Abstract HIV Y181C 0 5 11302824 4'-Ethynyl nucleoside analogs: potent inhibitors of multidrug-resistant human immunodeficiency virus variants in vitro. The 4'-E analogs also blocked the replication of a non-nucleoside reverse transcriptase inhibitor-resistant clone, HIV-1(Y181C), and showed an HIV-1 inhibition profile similar to that of zidovudine in time-of-drug-addition assays. 2001 Antimicrobial agents and chemotherapy Abstract HIV Y181C 121 126 NNRTI 51 87 11302824 4'-Ethynyl nucleoside analogs: potent inhibitors of multidrug-resistant human immunodeficiency virus variants in vitro. These 4'-E analogs also suppressed replication of various drug-resistant HIV-1 clones, including HIV-1(M41L/T215Y), HIV-1(K65R), HIV-1(L74V), HIV-1(M41L/T69S-S-G/T215Y), and HIV-1(A62V/V75I/F77L/F116Y/Q151M). 2001 Antimicrobial agents and chemotherapy Abstract HIV A62V;M41L;F116Y;F77L;Q151M;T215Y;T69S;V75I;M41L;T215Y;K65R;L74V 180;148;195;190;201;162;153;185;103;108;122;135 184;152;200;194;206;167;157;189;107;113;126;139 11311097 Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. The M184V lamivudine resistance mutation was detected at 6 weeks after delivery in specimens from 52 of 132 women. 2001 JAMA Abstract HIV M184V 4 9 11312344 Structural consequences of cyclophilin A binding on maturational refolding in human immunodeficiency virus type 1 capsid protein. Tryptophan 121 (W121) in CyP A distinguished the two proteins: a phenylalanine substitution (W121F) impaired binding of mature CA protein but not of Gag. 2001 Journal of virology Abstract HIV W121F 93 98 Gag;Capsid 149;127 152;129 11312671 Down-modulation of the costimulatory molecule, CD28, is a conserved activity of multiple SIV Nefs and is dependent on histidine 196 of Nef. Nef derived from SIVmacJ5 failed to down-modulate cell surface CD28, whereas a Q196H substitution mutant of SIVmacJ5 Nef was able to down-modulate cell surface CD28. 2001 Virology Abstract HIV Q196H 79 84 Nef;Nef 0;117 3;120 11316991 Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype. Lamivudine elicited the acquisition of the M184I mutation. 2001 AIDS (London, England) Abstract HIV M184I 43 48 11316991 Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype. OBJECTIVES: To investigate the genotypic and phenotypic effects of in vitro resistance selection with lamivudine and/or the second generation non-nucleoside reverse transcriptase inhibitor (NNRTI) quinoxaline HBY097 using HIV-1 isolates carrying the multi-nucleoside resistance pattern linked to the Q151M mutation. 2001 AIDS (London, England) Abstract HIV Q151M 300 305 NNRTI;NNRTI 142;190 178;195 11316991 Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype. Phenotypic resistance to all nucleoside-analog reverse transcriptase inhibitors (NRTIs) was increased when M184I was added to the multi-nucleoside resistance background in the absence of NNRTI-resistance mutations. 2001 AIDS (London, England) Abstract HIV M184I 107 112 RT;NNRTI;NRTI 47;187;81 68;192;86 11316991 Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype. The addition of the M184I mutation to the NNRTI-multi-nucleoside resistance set abolished this antagonizing effect for didanosine, zalcitabine and lamivudine, but further potentiated the phenotypic reversal for zidovudine and stavudine. 2001 AIDS (London, England) Abstract HIV M184I 20 25 NNRTI 42 47 11316997 HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort. However, the data suggest that some individuals (harboring a M184V mutation in RT or a V82I in protease) may have benefited from pre-therapy resistance tests. 2001 AIDS (London, England) Abstract HIV M184V;V82I 61;87 66;91 PR;RT 95;79 103;81 11321185 Resistance to (-)-2',3'-dideoxy-3'-thiacytidine (3TC) in HIV-1 isolated from paediatric patients. This was concomitant with the appearance of the M184V mutation in viral reverse transcriptase, previously shown to be responsiblefor such resistance. 1996 Antiviral therapy Abstract HIV M184V 48 53 RT 72 93 11322257 Replication of a pre-existing resistant HIV-1 subpopulation in vivo after introduction of a strong selective drug pressure. We analysed proviral DNA from nine previously untreated participants in a nevirapine study for the presence of the nevirapine resistance-conferring tyrosine to cysteine substitution at codon 181 of HIV-1 reverse transcriptase. 1996 Antiviral therapy Abstract HIV Y181C 148 194 RT 204 225 11324755 Genetic variability of HIV-1 protease from Nigeria and correlation with protease inhibitors drug resistance. The protease amino acid consensus sequence of the Nigerian subtype A are in complete agreement with the consensus A differing from the USA subtype B consensus in 10 positions (L10V, I13V, K14R, I15V, K20I, M36I, R41K, P63L, H69K and L89M). 2001 Virus genes Abstract HIV H69K;I13V;I15V;K14R;K20I;L10V;L89M;M36I;P63L;R41K 224;182;194;188;200;176;233;206;218;212 228;186;198;192;204;180;237;210;222;216 PR 4 12 11324755 Genetic variability of HIV-1 protease from Nigeria and correlation with protease inhibitors drug resistance. The secondary substitutions associated with protease inhibitor resistance were observed in all Nigerian sequences at the positions L10V, M36I and L89M. 2001 Virus genes Abstract HIV L10V;L89M;M36I 131;146;137 135;150;141 PR 44 52 11327441 A pilot study of a combination of three reverse transcriptase inhibitors in HIV-1 infection. Only one patient presented with a mutation resulting in the K219Q substitution, and one other with a T200I substitution. 1997 Antiviral therapy Abstract HIV K219Q;T200I 60;101 65;106 11327469 In vitro characterization of FIV-pPPR, a pathogenic molecular clone of feline immunodeficiency virus, and two drug-resistant pol gene mutants. A methionine-to-valine mutation at codon 183 (M183V) of the RT-encoding region of the pol gene of FIV-pPPR conferred high-level phenotypic resistance to 3TC and cross-resistance to the related compound (-)-beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine. 2001 American journal of veterinary research Abstract HIV M183V;M183V 46;2 51;44 Pol;RT 86;60 89;62 11327469 In vitro characterization of FIV-pPPR, a pathogenic molecular clone of feline immunodeficiency virus, and two drug-resistant pol gene mutants. IMPACT FOR HUMAN MEDICINE: 3TC resistance of FIV-pPPR M183V was similar in magnitude to that of HIV-1 M184V, a mutant described in infected humans treated with 3TC. 2001 American journal of veterinary research Abstract HIV M183V 54 59 11327469 In vitro characterization of FIV-pPPR, a pathogenic molecular clone of feline immunodeficiency virus, and two drug-resistant pol gene mutants. Thus, FIV-pPPR M183V may be a useful model for studying the in vivo effects of 3TC resistance on lentivirus pathogenesis. 2001 American journal of veterinary research Abstract HIV M183V 15 20 11333879 Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. 2001 Journal of virology Abstract HIV F227L;K103N;P225H;V106I;V108I;Y181C;Y188H;Y188L 77;238;66;38;45;52;59;247 82;243;71;43;50;57;64;252 11333879 Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear. 2001 Journal of virology Abstract HIV K103N;Y188L 82;91 87;96 11333879 Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. 2001 Journal of virology Abstract HIV G190S;K103N;Y188L 95;88;106 100;93;111 11333879 Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. 2001 Journal of virology Abstract HIV G190E;G190S;K103N;Y188L 320;320;303;310 327;327;308;315 RT 286 288 11333879 Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRTI), exhibited cross-resistance to all of the presently available NNRTIs (efavirenz, nevirapine, and delavirdine). 2001 Journal of virology Abstract HIV K103N;Y188L 13;22 18;27 NNRTI;NNRTI;RT 103;172;89 108;178;91 11340661 Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. Mutant K45I reduces the mobility of the flap and the inhibitor and contributes to an enhancement in structural stability and activity. 2001 Proteins Abstract HIV K45I 7 11 11340661 Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. Mutant L90M shows steric contacts with the catalytic Asp25 that could destabilize the catalytic loop at the dimer interface, leading to its observed decreased dimer stability and activity. 2001 Proteins Abstract HIV L90M 7 11 Asp 53 56 11340661 Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. Polar interactions in D30N are maintained, in agreement with the observed urea sensitivity. 2001 Proteins Abstract HIV D30N 22 26 11340661 Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. Structural changes seen in N88D are small; however, water molecules that mediate interactions between Asn88 and Thr74/Thr31/Asp30 in other complexes are missing in N88D. 2001 Proteins Abstract HIV N88D;N88D 27;164 31;168 Asp 124 127 11340661 Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. The side-chain variations at residue 30 relative to wild-type are the largest in D30N and the changes are consistent with the altered activity observed with peptide substrates. 2001 Proteins Abstract HIV D30N 81 85 11340661 Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. The side-chains of D30N and N88D are linked through a water molecule suggesting correlated changes at the two sites, as seen with clinical inhibitors. 2001 Proteins Abstract HIV D30N;N88D 19;28 23;32 11340661 Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. We have determined crystal structures of HIV-1 protease mutants, D30N, K45I, N88D, and L90M complexed with peptide inhibitor analogues of CA-p2 and p2-NC cleavage sites in the Gag-pol precursor in order to study the structural mechanisms underlying resistance. 2001 Proteins Abstract HIV D30N;K45I;L90M;N88D 65;71;87;77 69;75;91;81 PR;GagPol;NC;Capsid 47;176;151;138 55;183;153;140 11343221 Vertical transmission of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) and continued evolution of drug resistance in an HIV-1-infected infant. The infant had proviral DNA with evidence of RT mutations (M41L, L74V, and T215Y) and 3 PR substitutions (K20R, M36I, and V82A). 2001 The Journal of infectious diseases Abstract HIV K20R;L74V;M36I;M41L;T215Y;V82A 106;65;112;59;75;122 110;69;116;63;80;126 PR;RT 88;45 90;47 11344326 A general method for the quantitative analysis of functional chimeras: applications from site-directed mutagenesis and macromolecular association. Second, an I: value of 5.5 kcal/mol describes the effects of mirror mutations D94S (site 1) and S55D (site 2) in the Ca(2+) binding sites of oncomodulin on Ca(2+) affinity. 2001 Protein science Abstract HIV D94S;S55D 78;96 82;100 Capsid;Capsid 117;156 119;158 11344326 A general method for the quantitative analysis of functional chimeras: applications from site-directed mutagenesis and macromolecular association. The second mirror set, G98D (site 1) and D59G (site 2), yields a smaller impact (I: = -3.4 kcal/mol) on Ca(2+) binding; however, the effect is significantly more nearly context independent (C: = -0.6 versus C: = -2.7 kcal/mol). 2001 Protein science Abstract HIV D59G;G98D 41;23 45;27 Capsid 104 106 11344326 A general method for the quantitative analysis of functional chimeras: applications from site-directed mutagenesis and macromolecular association. The T109S mutation in AATase produces a nearly equal and opposite effect to S109T in TATase (C: < 0.4 kcal/mol). 2001 Protein science Abstract HIV S109T;T109S 76;4 81;9 11344527 Long-term benefit of genotypic-guided therapy and prevalence of multinucleoside resistance in an Italian group of antiretroviral multiexperienced patients. Among 432 patients failing antiretroviral therapy, five (1.15%) harboured viruses with Q151M mutation into the RT gene and no viruses were identified harbouring insertion at codon 69. 2001 Journal of clinical laboratory analysis Abstract HIV Q151M 87 92 RT 111 113 11344527 Long-term benefit of genotypic-guided therapy and prevalence of multinucleoside resistance in an Italian group of antiretroviral multiexperienced patients. Multiple nucleoside resistance involves specific genetic changes in the HIV-1 reverse transcriptase gene, such as Q151M mutation and an insertion of two serine aminoacids at RT codon 69. 2001 Journal of clinical laboratory analysis Abstract HIV Q151M 114 119 RT;RT 78;174 99;176 11353603 Alkylglycerol prodrugs of phosphonoformate are potent in vitro inhibitors of nucleoside-resistant human immunodeficiency virus type 1 and select for resistance mutations that suppress zidovudine resistance. Except for an HIV-1 variant encoding the K65R mutation in RT that exhibited 3.3- to 8.2-fold resistance, the nucleoside-resistant viruses included in the panel were sensitive to the PFA prodrugs (<3-fold increase in 50% inhibitory concentration), including multinucleoside-resistant variants encoding the Q151M complex of mutations or the T69S[SA] insert. 2001 Antimicrobial agents and chemotherapy Abstract HIV K65R;Q151M;T69S 41;305;339 45;310;343 RT 58 60 11353603 Alkylglycerol prodrugs of phosphonoformate are potent in vitro inhibitors of nucleoside-resistant human immunodeficiency virus type 1 and select for resistance mutations that suppress zidovudine resistance. Mutations detected in the resistant viruses were S117T, F160Y, and L214F (DB-PFA); M164I and L214F (MB-PFA); and W88G and L214F (EB-PFA). 2001 Antimicrobial agents and chemotherapy Abstract HIV F160Y;L214F;L214F;L214F;M164I;S117T;W88G 56;67;93;122;83;49;113 61;72;98;127;88;54;117 11353603 Alkylglycerol prodrugs of phosphonoformate are potent in vitro inhibitors of nucleoside-resistant human immunodeficiency virus type 1 and select for resistance mutations that suppress zidovudine resistance. The S117T, F160Y, and M164I mutations have not been previously identified. 2001 Antimicrobial agents and chemotherapy Abstract HIV F160Y;M164I;S117T 11;22;4 16;27;9 11353603 Alkylglycerol prodrugs of phosphonoformate are potent in vitro inhibitors of nucleoside-resistant human immunodeficiency virus type 1 and select for resistance mutations that suppress zidovudine resistance. When introduced into a zidovudine (AZT)-resistant background (67N 70R 215F 219Q), the W88G, S117T, F160Y, and M164I mutations reversed AZT resistance. 2001 Antimicrobial agents and chemotherapy Abstract HIV F160Y;M164I;S117T;W88G 99;110;92;86 104;115;97;90 11353634 Genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 variants with insertions or deletions in the reverse transcriptase (RT): multicenter study of patients treated with RT inhibitors. Resistance to AZT, d4T, and ABC could be found in the absence of the T215Y/F mutations. 2001 Antimicrobial agents and chemotherapy Abstract HIV T215F;T215Y 69;69 76;76 11353856 Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes. Another protease containing a subset of these amino acid polymorphisms (M36I/R41K/H69K/L89M), which are found in subtype C and other HIV subtypes, also was studied. 2001 Proc Natl Acad Sci U S A Abstract HIV M36I;H69K;L89M;R41K 72;82;87;77 76;86;91;81 PR 8 16 11353856 Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes. The A protease used in these studies differs in seven positions (I13V/E35D/M36I/R41K/R57K/H69K/L89M) in relation to the consensus B subtype protease. 2001 Proc Natl Acad Sci U S A Abstract HIV I13V;E35D;H69K;L89M;M36I;R41K;R57K 65;70;90;95;75;80;85 69;74;94;99;79;84;89 PR;PR 6;140 14;148 11354371 Synthesis and evaluation of efavirenz (Sustiva) analogues as HIV-1 reverse transcriptase inhibitors: replacement of the cyclopropylacetylene side chain. Several members of both series show equivalent potency to efavirenz against both wild-type virus and the key K103N mutant. 2001 Bioorganic & medicinal chemistry letters Abstract HIV K103N 109 114 11356952 Cooperation of the V1/V2 and V3 domains of human immunodeficiency virus type 1 gp120 for interaction with the CXCR4 receptor. Indeed, substitution of the LAI V3 loop or only its C-terminal part in the NDK gp 120 context was sufficient to restore usage of the HHRH, D193A, and D193R receptors. 2001 Journal of virology Abstract HIV D193A;D193R 139;150 144;155 11356952 Cooperation of the V1/V2 and V3 domains of human immunodeficiency virus type 1 gp120 for interaction with the CXCR4 receptor. The lack of activity toward the NDK strain of the HHRH chimeric CXCR4 in which the second extracellular loop (ECL2) derived from the rat CXCR4 and of CXCR4 with mutations at an aspartic acid in ECL2 (D193A and D193R) was apparently due to the sequence of the third variable loop (V3) of gp120, more precisely, to its C-terminal part. 2001 Journal of virology Abstract HIV D193A;D193R 200;210 206;215 gp120 287 292 11356952 Cooperation of the V1/V2 and V3 domains of human immunodeficiency virus type 1 gp120 for interaction with the CXCR4 receptor. The same result was achieved upon mutation of a single lysine residue of the NDK V3 loop to alanine (K319A) but not to arginine (K319R). 2001 Journal of virology Abstract HIV K319A;K319R 101;129 106;134 11356968 Augmentation of human immunodeficiency virus type 1 subtype E (CRF01_AE) multiple-drug resistance by insertion of a foreign 11-amino-acid fragment into the reverse transcriptase. Population-based sequence analyses of 82 independently cloned RT segments from the patient suggested that the variants with the insertion, three or four 3'-azido-3'-deoxythymidine resistance mutations, and a T69I mutation in combination had strong selective advantages during chemotherapy. 2001 Journal of virology Abstract HIV T69I 208 212 RT 62 64 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. Comparison of unliganded wild-type and Lys103Asn mutant HIV-1 RT structures reveals a network of hydrogen bonds in the Lys103Asn mutant that is not present in the wild-type enzyme. 2001 Journal of molecular biology Abstract HIV K103N;K103N 39;119 48;128 RT 62 64 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. Design of NNRTIs that make favorable interactions with the Asn103 side-chain should be relatively effective against the Lys103Asn drug-resistant mutant. 2001 Journal of molecular biology Abstract HIV K103N 120 129 NNRTI 10 16 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. Hydrogen bonds in the unliganded Lys103Asn mutant but not in wild-type HIV-1 RT are observed between (1) the side-chains of Asn103 and Tyr188 and (2) well-ordered water molecules in the pocket and nearby pocket residues. 2001 Journal of molecular biology Abstract HIV K103N 33 42 RT 77 79 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. Substitution of asparagine for lysine at position 103 of HIV-1 RT is associated with the development of resistance to NNRTIs; this mutation contributes to clinical failure of treatments employing NNRTIs. 2001 Journal of molecular biology Abstract HIV K103N 16 53 NNRTI;NNRTI;RT 118;196;63 124;202;65 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. The structural differences between unliganded wild-type and Lys103Asn mutant HIV-1 RT may correspond to stabilization of the closed-pocket form of the enzyme, which could interfere with the ability of inhibitors to bind to the enzyme. 2001 Journal of molecular biology Abstract HIV K103N 60 69 RT 83 85 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. The structures of wild-type and Lys103Asn mutant HIV-1 RT in complexes with NNRTIs are quite similar overall as well as in the vicinity of the bound NNRTIs. 2001 Journal of molecular biology Abstract HIV K103N 32 41 NNRTI;NNRTI;RT 76;149;55 82;155;57 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. These results are consistent with kinetic data indicating that NNRTIs bind more slowly to Lys103Asn mutant than to wild-type HIV-1 RT. 2001 Journal of molecular biology Abstract HIV K103N 90 99 NNRTI;RT 63;131 69;133 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. This novel drug-resistance mechanism explains the broad cross-resistance of Lys103Asn mutant HIV-1 RT to different classes of NNRTIs. 2001 Journal of molecular biology Abstract HIV K103N 76 85 NNRTI;RT 126;99 132;101 11371163 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. We have determined the structures of the unliganded form of the Lys103Asn mutant HIV-1 RT and in complexes with loviride and HBY 097. 2001 Journal of molecular biology Abstract HIV K103N 64 73 RT 87 89 11371689 HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir. CONCLUSIONS: Substantial decreases in plasma and CSF HIV-1 RNA following addition of ABC were not precluded by baseline HIV-1 NRTI-associated mutations, including the M184V mutation, but non-responders commonly harbored multiple ZDV/d4T-associated mutations. 2001 AIDS (London, England) Abstract HIV M184V 167 172 NRTI 126 130 11371689 HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir. RESULTS: Sixty out of sixty-seven subjects with baseline plasma HIV-RT sequence data harbored virus with > or = 1 NRTI-associated mutations; 50 out of 67 had the M184V mutation. 2001 AIDS (London, England) Abstract HIV M184V 162 167 NRTI;RT 114;68 118;70 11375057 Biological and genetic characterization of a human immunodeficiency virus strain resistant to CXCR4 antagonist T134. The trHIV-1(NL4-3) contained the following mutations in the V3 loop of gp120: N269K, Q278T, R279K, A284V, F285L, V286Y, I288T, K290E, N293D, M294I, and Q296K; an insertion of T at 290; and Delta274-275 (SI). 2001 AIDS research and human retroviruses Abstract HIV A284V;F285L;I288T;K290E;M294I;N269K;N293D;Q278T;Q296K;R279K;V286Y 99;106;120;127;141;78;134;85;152;92;113 104;111;125;132;146;83;139;90;157;97;118 gp120 71 76 11375059 An in vivo model for HIV resistance development. This resulted in the selection of mutants with Y181C and K103N changes in RT, which correspond to the HIV-1 mutations in nevirapine-resistant HIV-1 patients. 2001 AIDS research and human retroviruses Abstract HIV K103N;Y181C 57;47 62;52 RT 74 76 11377177 Structure-activity studies of FIV and HIV protease inhibitors containing allophenylnorstatine. VLE776 also exhibited potent antiviral activities against the drug-resistant HIV mutants (G48V and V82F) and the TL3-resistant HIV mutants. 2001 Bioorganic & medicinal chemistry Abstract HIV G48V;V82F 90;99 95;103 11378361 4,1-Benzoxazepinone analogues of efavirenz (Sustiva) as HIV-1 reverse transcriptase inhibitors. The best compounds are potent orally bioavailable inhibitors of both wild-type HIV-1 and its clinically relevant K103N mutant virus, but are highly protein-bound in human plasma. 2001 Bioorganic & medicinal chemistry letters Abstract HIV K103N 113 118 11384227 Basic amino acid residues in the V3 loop of simian immunodeficiency virus envelope alter viral coreceptor tropism and infectivity but do not allow efficient utilization of CXCR4 as entry cofactor. A single amino acid substitution of L328R, located near the tip of the V3 loop, resulted in grossly reduced Env expression levels and impaired viral infectivity. 2001 Virology Abstract HIV L328R 36 41 Env 108 111 11384227 Basic amino acid residues in the V3 loop of simian immunodeficiency virus envelope alter viral coreceptor tropism and infectivity but do not allow efficient utilization of CXCR4 as entry cofactor. In comparison to the L328R mutation, changes of P334K and D337K had little disruptive effects on SIVmac entry and replication. 2001 Virology Abstract HIV D337K;L328R;P334K 58;21;48 63;26;53 11384227 Basic amino acid residues in the V3 loop of simian immunodeficiency virus envelope alter viral coreceptor tropism and infectivity but do not allow efficient utilization of CXCR4 as entry cofactor. Interestingly, mutation of L320K and P321R disrupted coreceptor usage of GPR15 but not R5. 2001 Virology Abstract HIV L320K;P321R 27;37 32;42 11384233 2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1. However, they showed a lack of activity against the K103N and Y181C mutant viruses. 2001 Journal of medicinal chemistry Abstract HIV K103N;Y181C 52;62 57;67 11384233 2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1. When gauged for their broad-spectrum antiviral activity against key non-nucleoside reverse transcriptase inhibitor (NNRTI) related mutants, all the di-meta-substituted sulfones 3u-z and the 2-naphthyl analogue 3ee generally showed single-digit nanomolar activity against the V106A and P236L strains and submicromolar to low nanomolar activity against strains E138K, V108I, and Y188C. 2001 Journal of medicinal chemistry Abstract HIV E138K;P236L;V106A;V108I;Y188C 359;285;275;366;377 364;290;280;371;382 NNRTI;NNRTI 68;116 104;121 11389511 Prevalence of the T215Y mutation in human immunodeficiency virus type 1-infected pregnant women in a New York cohort, 1995--1999. From 1997 through 1999, the prevalence of the zidovudine resistance mutation T215Y was 9.7% among pregnant women, and the human immunodeficiency virus type 1 (HIV-1) load in those with resistant virus was higher than that measured in women with wild-type HIV-1. 2001 Clinical infectious diseases Abstract HIV T215Y 77 82 11391165 A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir. The protease I50V mutation characteristic of APV resistance was not observed, although other key PI mutations were selected in 4 patients failing therapy, 2 of whom had PI resistance at baseline. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I50V 13 17 PR;PI;PI 4;97;169 12;99;171 11391172 Resistance to antiretroviral therapy among patients in Uganda. Among 8 patients taking lamivudine, phenotypic resistance was found for 9 (90%) of 10 specimens and was associated with an M184V mutation in all nine cases. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 123 128 11391173 High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Cote d'Ivoire. The prevalence of mutations associated with resistance to ARV drugs was: 29 (42.6%) to zidovudine, 10 (14.7%) to lamivudine, one (1.5%) to didanosine, one K103N mutation (associated with resistance to delavirdine, nevirapine, and efavirenz), one Y181C mutation (associated with resistance to delavirdine and nevirapine), two to both indinavir (M46I/L and V82A) and saquinavir (G48V and L90M), and one each to ritonavir (V82A) and nelfinavir (D30N). 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D30N;G48V;K103N;L90M;M46I;M46L;V82A;V82A;Y181C 442;377;155;386;344;344;355;420;246 446;382;160;390;351;351;359;424;251 11396919 The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design. In this paper the binding thermodynamics of KNI-764 to the wild-type and drug-resistant mutant V82F/I84V are presented and the results compared to those obtained with existing clinical inhibitors. 2001 Archives of biochemistry and biophysics Abstract HIV I84V;V82F 100;95 104;99 11396919 The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design. The resistant mutation V82F/I84V lowers the binding affinity of KNI-764 26-fold, which can be accounted almost entirely by a less favorable binding enthalpy to the mutant. 2001 Archives of biochemistry and biophysics Abstract HIV I84V;V82F 28;23 32;27 11401293 HIV-1 reverse transcriptase interaction with model RNA-DNA duplexes. Binding of the p66(E478Q)/p51 to any RNA-DNA hybrids is slightly stronger compared with wild type. 2001 Analytical biochemistry Abstract HIV E478Q 19 24 11401293 HIV-1 reverse transcriptase interaction with model RNA-DNA duplexes. For the p66(E478Q)/p51 enzyme, orientation effects are notable even altering the K(D) value. 2001 Analytical biochemistry Abstract HIV E478Q 12 17 11401293 HIV-1 reverse transcriptase interaction with model RNA-DNA duplexes. Parameters of interaction between model substrates (ligands) and HIV-1 RT (wild type p66/p51 and the RNase H-deficient mutant p66(E478Q)/p51) (analytes) were estimated by surface plasmon resonance at 25 degrees C, pH 8.0. 2001 Analytical biochemistry Abstract HIV E478Q 130 135 RT 71 73 11408240 Biochemical mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to stavudine. RT from site-directed mutants with 69S-XX codon insertions and/or conventional zidovudine resistance mutations seems to be involved in an ATP-dependent resistance mechanism analogous to pyrophosphorolysis, whereas the mechanism for RT with the Q151M or V75T mutation appears to be independent of added ATP for reducing binding to d4T-triphosphate. 2001 Antimicrobial agents and chemotherapy Abstract HIV Q151M;V75T 244;253 249;257 RT;RT 0;232 2;234 11413308 Changes in human immunodeficiency virus type 1 populations after treatment interruption in patients failing antiretroviral therapy. Among 12 patients with viruses expressing the V82A or L90M resistance mutation who had undergone a 3-month interruption of therapy and for whom conventional genotyping had revealed an apparent total reconversion to wild-type virus, minority populations expressing these mutations, representing 0.1 to 21% of total virus, were still detectable in 9 cases. 2001 Journal of virology Abstract HIV L90M;V82A 54;46 58;50 11413321 Replication of phenotypically mixed human immunodeficiency virus type 1 virions containing catalytically active and catalytically inactive reverse transcriptase. As expected, based on previous work with murine leukemia virus, there was relatively inefficient virus replication when the RNase H and polymerase activities were encoded on separate vectors (D110E plus E478Q and D110E plus D443A). 2001 Journal of virology Abstract HIV D110E;D110E;D443A;E478Q 192;213;224;203 198;218;229;208 Pol 136 146 11413321 Replication of phenotypically mixed human immunodeficiency virus type 1 virions containing catalytically active and catalytically inactive reverse transcriptase. If the E478Q mutation was used to reduce RNase H activity, the number of reverse transcripts that were initiated was reduced; there was also a strong effect on minus-strand transfer. 2001 Journal of virology Abstract HIV E478Q 7 12 11413321 Replication of phenotypically mixed human immunodeficiency virus type 1 virions containing catalytically active and catalytically inactive reverse transcriptase. Vectors containing wild-type reverse transcriptase (RT), vectors encoding the D110E mutation to inactivate polymerase, and vectors encoding mutations D443A and E478Q to inactivate RNase H were constructed. 2001 Journal of virology Abstract HIV D110E;D443A;E478Q 78;150;160 83;155;165 RT;Pol;RT 29;107;52 50;117;54 11413327 Nef from human immunodeficiency virus type 1(F12) inhibits viral production and infectivity. Importantly, the introduction of one of these mutations (E177G) into Nef from HIV-1(NL4-3) also created a dominant-negative Nef protein. 2001 Journal of virology Abstract HIV E177G 57 62 Nef;Nef 69;124 72;127 11417760 Virological response in multidrug-experienced HIV-1-infected subjects failing highly active combination regimens after shifting from lamivudine to didanosine. At the time of the regimen shift, all the subjects exhibited a high-level phenotypic resistance to both zidovudine and lamivudine with changes at codons 70-219 in 100% of cases, at codon 215 in 13 of 16 patients, and the M184V substitution in 13/16 patients. 2001 Antiviral therapy Abstract HIV M184V 221 226 11417760 Virological response in multidrug-experienced HIV-1-infected subjects failing highly active combination regimens after shifting from lamivudine to didanosine. These findings suggest the possibility of achieving a viral load response to didanosine-containing regimens in patients with reverse transcriptase (RT) M184V mutations who were previously treated with this drug and its possible use in salvage combinations. 2001 Antiviral therapy Abstract HIV M184V 152 157 RT;RT 125;148 146;150 11417763 Prevalence of genotypic resistance among antiretroviral drug-naive HIV-1-infected patients in Belgium. No patients displayed the multi-nucleoside resistance Q151M mutation. 2001 Antiviral therapy Abstract HIV Q151M 54 59 11417764 Resistance profiles to antiretroviral drugs in HIV-1 drug-naive patients in Argentina. In the viral protease region, 1/86 (1.2%) individuals carried the D30N mutation, whereas 1/85 (1.2%) had the M41L mutation in the reverse transcriptase (RT) region. 2001 Antiviral therapy Abstract HIV D30N;M41L 66;109 70;113 RT;PR;RT 130;13;153 151;21;155 11418520 Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors. Group B patients had the highest prevalence of K103N+/Y181C. 2001 The Journal of antimicrobial chemotherapy Abstract HIV K103N;Y181C 47;54 52;59 11418520 Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors. In conclusion, zidovudine seems not to determine the emergence of K103N; however, there appears to be an accumulation of NNRTI resistance mutations with sequential use of NNRTIs. 2001 The Journal of antimicrobial chemotherapy Abstract HIV K103N 66 71 NNRTI;NNRTI 121;171 126;177 11418520 Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors. No difference was found in the exposure to zidovudine or major zidovudine mutations between the resistance patterns K103N-/Y181C+, K103N+/Y181C- and K103N+/ Y181C+, either in group A (patients on nevirapine and previously NNRTI naive) or in group B (on any NNRTI and experience of two or more NNRTIs including nevirapine). 2001 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K103N;K103N;Y181C;Y181C;Y181C 116;131;149;123;138;157 121;136;154;128;143;162 NNRTI;NNRTI;NNRTI 222;257;293 227;262;299 11418520 Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors. Our aim was to identify whether zidovudine has a role in the emergence of the K103N resistance mutation in the HIV-1 reverse transcriptase gene on non-nucleoside reverse transcriptase inhibitors (NNRTIs). 2001 The Journal of antimicrobial chemotherapy Abstract HIV K103N 78 83 NNRTI;RT;NNRTI 147;117;196 183;138;202 11426943 Analysis of apoptosis induced by HIV-1 Vpr and examination of the possible role of the hHR23A protein. This is exemplified by a C-terminal mutant, R80A, that does not arrest cells, yet induces low but significant levels of apoptosis. 2001 Experimental cell research Abstract HIV R80A 44 48 11427587 Resistance-associated mutations in the human immunodeficiency virus type 1 subtype c protease gene from treated and untreated patients in the United Kingdom. D30N, M46I, V82A/F, and I84V were seen rarely. 2001 Journal of clinical microbiology Abstract HIV I84V;M46I;V82A;V82F;D30N 24;6;12;12;0 28;10;18;18;4 11427587 Resistance-associated mutations in the human immunodeficiency virus type 1 subtype c protease gene from treated and untreated patients in the United Kingdom. M36I and I93L mutations were observed in nearly all samples from both treated and untreated patients and so cannot be considered as resistance-associated mutations in this subtype. 2001 Journal of clinical microbiology Abstract HIV I93L;M36I 9;0 13;4 11427587 Resistance-associated mutations in the human immunodeficiency virus type 1 subtype c protease gene from treated and untreated patients in the United Kingdom. The most common primary mutation observed in treated patients was L90M. 2001 Journal of clinical microbiology Abstract HIV L90M 66 70 11435562 Gag-Pol supplied in trans is efficiently packaged and supports viral function in human immunodeficiency virus type 1. The Gag-Pol proteins were either immunotagged with a His epitope or functionally tagged with a mutation (K65R) in reverse transcriptase that is associated with drug resistance. 2001 Journal of virology Abstract HIV K65R 105 109 RT;GagPol 114;4 135;11 11435564 Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions. More surprising was the isolation of suppressors of the R170Q and L171V MHR mutations, which mapped to the N-terminal domain of the CA protein. 2001 Journal of virology Abstract HIV L171V;R170Q 66;56 71;61 Capsid 132 134 11435564 Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions. The F167Y defect could also be repaired by a second, independent suppressor in the C-terminal SP that was removed from CA during maturation. 2001 Journal of virology Abstract HIV F167Y 4 9 Capsid 119 121 11435564 Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions. The F167Y mutation in the MHR was fully suppressed by a single amino acid change in the alpha helix immediately downstream of the MHR, a region that forms the major dimer interface in human immunodeficiency virus CA. 2001 Journal of virology Abstract HIV F167Y 4 9 Capsid 213 215 11435564 Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions. This finding suggests that the F167Y mutation indirectly interfered with dimerization. 2001 Journal of virology Abstract HIV F167Y 31 36 11435564 Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions. This single residue change, which increased the rate of SP cleavage, apparently corrected the F167Y defect by modifying the maturation pathway. 2001 Journal of virology Abstract HIV F167Y 94 99 11435603 Correlation between viral resistance to zidovudine and resistance at the reverse transcriptase level for a panel of human immunodeficiency virus type 1 mutants. The ATP-dependent mechanism (analogous to pyrophosphorolysis) appears to be dominant in the mutants bearing the D67N and K70R or 69 insertion mutations, whereas the Q151M mutation seems independent of ATP for decreased binding to AZT-triphosphate. 2001 Journal of virology Abstract HIV D67N;K70R;Q151M 112;121;165 116;125;170 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. However, a minority of patients on delavirdine therapy still have isolates with P236L. 2001 Virology Abstract HIV P236L 80 85 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. In contrast, three of five clones that did not have P236L (but had either K103N or Y181C) replicated significantly better than NL4-3 with P236L. 2001 Virology Abstract HIV K103N;P236L;P236L;Y181C 74;52;138;83 79;57;143;88 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. Nine of 10 patient-derived clones containing P236L replicated as slowly as NL4-3 with P236L. 2001 Virology Abstract HIV P236L;P236L 45;86 50;91 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. Other NNRTI-resistance mutations, such as K103N and Y181C, do not reduce the replication capacity of NL4-3 as much as P236L and develop more frequently in HIV-1 isolates from patients failing delavirdine. 2001 Virology Abstract HIV K103N;P236L;Y181C 42;118;52 47;123;57 NNRTI 6 11 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. Thus, the majority of patients who acquire P236L during delavirdine therapy do not have RT mutations that compensate for the replication defect conferred by P236L. 2001 Virology Abstract HIV P236L;P236L 43;157 48;162 RT 88 90 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. We have shown that the HIV-1 laboratory strain NL4-3 that contains P236L [a reverse transcriptase mutation conferring resistance to the nonnucleoside reverse transcriptase inhibitor (NRTI) delavirdine] replicates more slowly than wild-type NL4-3. 2001 Virology Abstract HIV P236L 67 72 NNRTI;RT;NRTI 136;76;183 171;97;187 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. We hypothesize that HIV-1 isolates with P236L may have a compensatory mutation outside RT. 2001 Virology Abstract HIV P236L 40 45 RT 87 89 11437654 Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. We postulated that reverse transcriptase (RT) sequences from these patient isolates contain other mutations that compensate for the adverse effect of P236L. 2001 Virology Abstract HIV P236L 150 155 RT;RT 19;42 40;44 11451685 Variants other than aspartic acid at codon 69 of the human immunodeficiency virus type 1 reverse transcriptase gene affect susceptibility to nuleoside analogs. The T69D mutation in the human immunodeficiency virus type 1 reverse transcriptase (RT) gene has been associated with reduced susceptibility to dideoxycytosine (ddC); however, several other mutations at codon 69 have been observed in antiretroviral drug-treated patients. 2001 Antimicrobial agents and chemotherapy Abstract HIV T69D 4 8 RT;RT 61;84 82;86 11451685 Variants other than aspartic acid at codon 69 of the human immunodeficiency virus type 1 reverse transcriptase gene affect susceptibility to nuleoside analogs. These results suggest that the T69D mutation is not the only codon 69 variant associated with drug resistance and that ddC is not the only drug affected. 2001 Antimicrobial agents and chemotherapy Abstract HIV T69D 31 35 11451685 Variants other than aspartic acid at codon 69 of the human immunodeficiency virus type 1 reverse transcriptase gene affect susceptibility to nuleoside analogs. These variants included T69N, -S, -A, -G, -E, -I, and -K mutations that were present in patients treated with NRTI but not in drug-naive patients. 2001 Antimicrobial agents and chemotherapy Abstract HIV T69N 24 28 NRTI 110 114 11459666 Synthesis and evaluation of novel quinolinones as HIV-1 reverse transcriptase inhibitors. The C-3 substituted compound 9h displayed improved antiviral activity against clinically significant single (K103N) and double (K103N/L100I) mutant viruses. 2001 Bioorganic & medicinal chemistry letters Abstract HIV K103N;K103N;L100I 128;109;134 133;114;139 11461677 Low conservation of functional domains of HIV type 1 vif and vpr genes in infected mothers correlates with lack of vertical transmission. For vif sequences, NT-2 contained stop codons and no initiation codons, whereas NT-1 sequences carried a substitution of a highly conserved tyrosine to histidine at position 30. 2001 AIDS research and human retroviruses Abstract HIV Y30H 140 176 Vif 4 7 11461677 Low conservation of functional domains of HIV type 1 vif and vpr genes in infected mothers correlates with lack of vertical transmission. Similarly, the vpr sequences of NT-2 contained stop codons and no initiation codons, NT-4 contained a substitution of serine in place of alanine at position 30, some NT-1 sequences substituted arginine in place of glycine at position 75, and NT-3 sequences presented a deletion in the C terminus that was absent in transmitting mother and consensus subtype B sequences and is essential for Vpr function. 2001 AIDS research and human retroviruses Abstract HIV A30S;G75R 118;193 159;236 Vpr;Vpr 15;390 18;393 11461996 Hydrophobic amino acids in the human immunodeficiency virus type 1 p2 and nucleocapsid proteins can contribute to the rescue of deleted viral RNA packaging signals. Compensation studies have identified two second-site mutations, namely, MP2 (a T12I substitution in p2) and MNC (a T24I substitution in the nucleocapsid [NC] protein) that were involved in the rescue of various deletions in the aforementioned RNA region (i.e., BH-D1, BH-D2, and BH-LD3). 2001 Journal of virology Abstract HIV T12I;T24I 79;115 83;119 NC 154 156 11462018 Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients. Mutations at positions 82, 54, 10, 63, 71, and 84 were most closely associated with relatively modest (4- and 10-fold) changes in phenotype, while the K20M/R and F53L mutations, in conjunction with multiple other mutations, were associated with >20- and >40-fold-reduced susceptibility, respectively. 2001 Journal of virology Abstract HIV F53L;K20M;K20R 162;151;151 166;157;157 11462018 Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients. Two statistical tests showed that specific mutations at 11 amino acid positions in protease (L10F/I/R/V, K20M/R, L24I, M46I/L, F53L, I54L/T/V, L63P, A71I/L/T/V, V82A/F/T, I84V, and L90M) were associated with reduced susceptibility. 2001 Journal of virology Abstract HIV A71I;A71L;A71T;A71V;F53L;I54L;I54T;I54V;I84V;K20M;K20R;L10F;L10I;L10R;L10V;L24I;L63P;L90M;M46I;M46L;V82A;V82F;V82T 149;149;149;149;127;133;133;133;171;105;105;93;93;93;93;113;143;181;119;119;161;161;161 159;159;159;159;131;141;141;141;175;111;111;103;103;103;103;117;147;185;125;125;169;169;169 PR 83 91 11468426 Genotypic correlates of a virologic response to stavudine after zidovudine monotherapy. Seven of the 8 responders had only a K70R mutation at baseline. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R 37 41 11470872 Reverse transcriptase incorporation of 1,5-anhydrohexitol nucleotides. Investigation of incorporation of the altritol anhydrohexitol nucleotide of adenine in the presence of M184V and Vent (exo(-)) DNA polymerase proved that an adjacent hydroxyl group on C3 of 1,5-anhydrohexitol-ATP has a detrimental effect on the substrate activity of the six-ring analogue. 2001 Nucleic acids research Abstract HIV M184V 103 108 Pol 131 141 11470872 Reverse transcriptase incorporation of 1,5-anhydrohexitol nucleotides. Subsequently, several HIV-1 mutants (4xAZT, 4xAZT/L100I, L74V, M184V and K65A) were likewise analysed, resulting in selection of K65A and, in particular, M184V as the most succesful mutant HIV-1 reverse transcriptases capable of elongating a DNA primer with several 1,5-anhydrohexitol adenines in an efficient way. 2001 Nucleic acids research Abstract HIV K65A;K65A;L100I;L74V;M184V;M184V 73;129;50;57;63;154 77;133;55;61;68;159 RT 195 217 11491416 Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. Although increased removal of chain-terminating inhibitors by pyrophosphorolysis and ATP-dependent unblocking correlated with reduced susceptibility of viruses with zidovudine-associated mutations, a reduction in the removal of chain-terminators was not observed, which would explain the increased drug susceptibility of mutants containing M184V plus zidovudine-associated mutations. 2001 Antiviral therapy Abstract HIV M184V 340 345 11491416 Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. An enzymatic analysis was undertaken to elucidate the mechanisms of altered drug susceptibilities of HIV-1 containing zidovudine-associated mutations in the presence or absence of M184V. 2001 Antiviral therapy Abstract HIV M184V 180 185 11491416 Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. However, analyses of single-cycle processivity of the mutant RT enzymes on heteropolymeric RNA templates showed that all M184V-containing mutant RT enzymes were less processive than wild-type RT, most notably for mutants expressing both zidovudine-associated mutations and M184V. 2001 Antiviral therapy Abstract HIV M184V;M184V 121;273 126;278 RT;RT;RT 61;145;192 63;147;194 11491416 Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. Similarly, the in vitro replication capacity of a mutant virus expressing a zidovudine-associated mutation and M184V was significantly reduced compared with wild-type virus. 2001 Antiviral therapy Abstract HIV M184V 111 116 11491416 Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. The observed decrease in enzymatic processivity of the M184V-expressing RT enzymes might result in decreased viral replication, which then might contribute to the increased drug susceptibility of HIV-1 expressing these RT mutations. 2001 Antiviral therapy Abstract HIV M184V 55 60 RT;RT 72;219 74;221 11491416 Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. The presence of the HIV reverse transcriptase (RT) resistance mutation, M184V, induced by lamivudine and abacavir treatment results in increased tenofovir, adefovir and zidovudine susceptibility for HIV-1 with zidovudine-associated RT mutations in vitro. 2001 Antiviral therapy Abstract HIV M184V 72 77 RT;RT;RT 24;47;232 45;49;234 11491418 Treatment intensification with abacavir in HIV-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment. Adding abacavir to Combivir can be a safe and effective therapeutic option for patients, including those harbouring virus with the M184V mutation. 2001 Antiviral therapy Abstract HIV M184V 131 136 11491418 Treatment intensification with abacavir in HIV-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment. An identical proportion of patients (74%) in each treatment group harboured virus with the M184V mutation after 12 weeks. 2001 Antiviral therapy Abstract HIV M184V 91 96 11491418 Treatment intensification with abacavir in HIV-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment. At the time of intensification with abacavir, all 35 patients with evaluable isolates harboured HIV-1 containing M184V. 2001 Antiviral therapy Abstract HIV M184V 113 118 11504476 HIV resistance to zidovudine: the role of pyrophosphorolysis. The D67N/K70R mutations result in a significantly increased rate of RT-catalyzed pyrophosphorolysis at physiological levels of pyrophosphate, which leads to a decrease in the extent of AZT chain termination of nascent viral DNA. 1999 Drug resistance updates Abstract HIV D67N;K70R 4;9 8;13 RT 68 70 11504476 HIV resistance to zidovudine: the role of pyrophosphorolysis. The potential replication deficit of an increased reverse reaction during DNA synthesis is compensated by increased DNA synthesis processivity, a phenotype that results from the T215F/Y/K219Q mutations in RT. 1999 Drug resistance updates Abstract HIV K219Q;T215F;T215Y 186;178;178 191;185;185 RT 205 207 11504476 HIV resistance to zidovudine: the role of pyrophosphorolysis. While this resistance could be unequivocally correlated with multiple mutations in HIV reverse transcriptase (D67N, K70R, T215F/Y, K219Q), the mechanism or phenotype for this resistance has remained obscure for more than a decade, despite active investigation. 1999 Drug resistance updates Abstract HIV D67N;K219Q;K70R;T215F;T215Y 110;131;116;122;122 114;136;120;129;129 RT 87 108 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. However, in addition to the Trp229Tyr mutation this mutant virus also contained an Ile63Met, a Val189Ile, and a Glu396Gly mutation in its RT. 2001 Virology Abstract HIV E396G;I63M;V189I;W229Y 112;83;95;28 121;91;104;37 RT 138 140 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. It is also an important constituent of the so-called "primer grip." Using a recombinant virus assay, we tried to obtain recombinant virus containing a Trp229Phe or a Trp229Tyr mutation in its RT. 2001 Virology Abstract HIV W229F;W229Y 151;166 160;175 RT 192 194 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. Kinetic analysis revealed that both template/primer binding and dNTP incorporation are affected by the Trp229Tyr mutation. 2001 Virology Abstract HIV W229Y 103 112 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. Previous studies already established the very low DNA polymerase activities of both the Trp229Phe and the Trp229Tyr mutant RT enzymes. 2001 Virology Abstract HIV W229F;W229Y 88;106 97;115 Pol;RT 54;123 64;125 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. We found that the three additional mutations partly restored the low RNA- and DNA-dependent DNA polymerase activities of the Trp229Tyr mutant enzyme. 2001 Virology Abstract HIV W229Y 125 134 Pol 96 106 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. We were able to obtain a Trp229Tyr but not a Trp229Phe mutant virus. 2001 Virology Abstract HIV W229F;W229Y 45;25 54;34 11504549 Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a Trp229Tyr mutant RT. When we evaluated the quadruple mutant virus for sensitivity/resistance against a variety of NNRTIs, no significant difference with the sensitivity/resistance profile of the single Trp229Tyr mutant RT enzyme could be observed. 2001 Virology Abstract HIV W229Y 181 190 NNRTI;RT 93;198 99;200 11504976 Genotypic variation of HIV-1 reverse transcriptase and protease: comparative analysis of clade C and clade B. Most clade C viruses also showed significant differences from clade B consensus sequence at additional protease sites: R41K 100%, H69K/Q 85%, L89M 95% and I93L 80% (P < 0.0001). 2001 AIDS (London, England) Abstract HIV H69K;H69Q;I93L;L89M;R41K 130;130;155;142;119 136;136;159;146;123 PR 103 111 11504976 Genotypic variation of HIV-1 reverse transcriptase and protease: comparative analysis of clade C and clade B. RESULTS: There were 87 clade B (14 naive) and 78 clade C (20 naive) [corrected] with significant differences in the prevalence of known drug-resistance mutations between the clades: in naive patients in the protease region M36I 7% and 95% (P < 0.0001), K20R 0% and 27% (P = 0.063), A71V 18% and 0% (P = 0.063), M46I 0% and 13%, and V77I 18% and 0% (P = 0.063), respectively, and in the reverse transcriptase region A98G/S 0% and 20% (P = 0.12), respectively. 2001 AIDS (London, England) Abstract HIV A71V;A98G;A98S;K20R;M36I;M46I;V77I 282;415;415;253;223;311;332 286;421;421;257;227;315;336 RT;PR 386;207 407;215 11504976 Genotypic variation of HIV-1 reverse transcriptase and protease: comparative analysis of clade C and clade B. There were also significant differences (P < 0.03 to < 0.0001) in treated patients in clades B and C: in the protease region L10I 40% and 12%, M36I 26% and 95%, L63P 67% and 40%, A71I 38% and 7%, G73I and V77I 18% and 0%, I84V 16% and 3%, and L90M 40% and 12%, respectively; in the reverse transcriptase M41L 41% and 17%, D67N 41% and12%, K70R 30% and 7%, T215Y 48% and 29%, K219Q 21% and 7%, and A98G/S 3% and 24%, respectively. 2001 AIDS (London, England) Abstract HIV A71I;A98G;A98S;D67N;G73I;I84V;K219Q;K70R;L10I;L63P;L90M;M36I;M41L;T215Y;V77I 179;397;397;322;196;222;375;339;125;161;243;143;304;356;205 183;403;403;326;200;226;380;343;129;165;247;147;308;361;209 RT;PR 282;109 303;117 11506064 HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. Another two patients partially responded to salvage regimens, both virologically and immunologically, and harboured the M184V mut in the RT gene. 2001 Microbios Abstract HIV M184V 120 125 RT 137 139 11506064 HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. In the present study three out of 350 (0.85%) of HIV-infected patients who underwent a drug-resistance genotyping assay because of therapeutic failure showed the Q151M mut. 2001 Microbios Abstract HIV Q151M 162 167 HIV infections 49 61 11506064 HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. One such patient failed to respond to all salvage regimens tried and was shown to harbour some of the characteristic mut associated with Q151M (77L and 116Y). 2001 Microbios Abstract HIV Q151M 137 142 11506064 HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. The M184V mut seemed to confer some viro-immunological benefit when associated with the Q151M mutation, compared with the latter alone. 2001 Microbios Abstract HIV M184V;Q151M 4;88 9;93 11506064 HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. The prevalence and clinical implications of the Q151M multidrug-resistance mutation gene (mut) to antiretroviral drugs in the HIV reverse transcriptase (RT) gene have not yet been fully explained. 2001 Microbios Abstract HIV Q151M 48 53 RT;RT 130;153 151;155 11506064 HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated resistance mutations and response to antiretroviral salvage treatment. The prevalence of Q151M mut in our group was less (0.85%) than in other studies, which ranged from 2 to 19%. 2001 Microbios Abstract HIV Q151M 18 23 11511821 Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir dipivoxil therapy: genotypic and phenotypic analyses of study GS-96-408. Most mutations were typical zidovudine (ZDV)-resistance mutations (e.g., M41L, D67N, K70R, T215Y) in patients taking ZDV or stavudine (d4T) concomitantly, demonstrating directly in the placebo arm that d4T is able to select for these mutations. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D67N;K70R;M41L;T215Y 79;85;73;91 83;89;77;96 11511821 Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir dipivoxil therapy: genotypic and phenotypic analyses of study GS-96-408. RT mutations previously selected by adefovir in vitro (K70E or K65R) did not develop in any patient. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;K70E 63;55 67;60 RT 0 2 11511821 Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir dipivoxil therapy: genotypic and phenotypic analyses of study GS-96-408. There appeared to be more patients developing D67N and K70R mutations in the ADV arm versus more T215Y mutations in the placebo arm. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D67N;K70R;T215Y 46;55;97 50;59;102 11517441 Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine. In group 2, all isolates carried the M184V mutation. 2001 The Journal of infectious diseases Abstract HIV M184V 37 42 11517441 Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine. The T215Y mutation emerged in 13 (61.9%) and 2 (9.5%) isolates in groups 1 and 2, respectively (P < .0001). 2001 The Journal of infectious diseases Abstract HIV T215Y 4 9 11522180 Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolated from zidovudine-naive patients experiencing viremia on stavudine-containing regimens. Of these, 24 samples (28%) had TAMs, and 30 samples (35%) had either TAMs and/or the Q151M multinucleoside resistance (MNR) mutation. 2001 AIDS research and human retroviruses Abstract HIV Q151M 85 90 11522180 Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolated from zidovudine-naive patients experiencing viremia on stavudine-containing regimens. Studies have demonstrated that HIV-1 isolated from subjects experiencing virologic failure on stavudine (d4T)-containing regimens often contains thymidine analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with zidovudine (ZDV) resistance. 2001 AIDS research and human retroviruses Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 237;269;269;243;249;231;256;256 241;276;276;247;254;235;263;263 RT;RT 194;217 215;219 11525746 A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells. Here, we report that a natural variability in the proline-rich motif (R71T) profoundly modulated Nef-stimulated viral replication in primary T cells of immature dendritic cell/T cell cocultures. 2001 Current biology Abstract HIV R71T 70 74 Nef 97 100 11533199 Human immunodeficiency virus type 1 N-terminal capsid mutants that exhibit aberrant core morphology and are blocked in initiation of reverse transcription in infected cells. We also constructed a third mutant, D51A, which has a mutation that destroys a salt bridge between Pro1 and Asp51. 2001 Journal of virology Abstract HIV D51A 36 40 Asp 108 111 11536226 Replicative fitness in vivo of HIV-1 variants with multiple drug resistance-associated mutations. The least fit viruses were associated with the RT mutation M184I/V (11.6% less fit) and the PR mutations D30N (12.4% less fit) and M46I/L (21% less fit). 2001 Journal of medical virology Abstract HIV D30N;M184I;M184V;M46I;M46L 105;59;59;131;131 109;66;66;137;137 PR;RT 92;47 94;49 11551942 Structural and functional characterization of human CXCR4 as a chemokine receptor and HIV-1 co-receptor by mutagenesis and molecular modeling studies. With site-directed mutagenesis, we have identified that the amino acid residues Asp (D20A) and Tyr (Y21A) in the N-terminal domain and the residue Glu (E268A) in extracellular loop 3 (ECL3) are involved in ligand binding, whereas the mutation Y190A in extracellular loop 2 (ECL2) impairs the signaling mediated by SDF-1alpha. 2001 The Journal of biological chemistry Abstract HIV D20A;E268A;Y190A;Y21A 85;152;243;100 89;157;248;104 Asp 80 83 11559430 Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine. A novel deletion of residue 69 of the HIV-1 reverse transcriptase (RT) gene was detected in combination with mutations V75I/V and F77L/F in a patient with partial virological response to several antiretroviral drug regimens, including stavudine (D4T), didanosine (DDI), lamivudine (3TC), saquinavir (SQV), and nevirapine (NVP). 2001 AIDS research and human retroviruses Abstract HIV F77F;F77L;V75I;V75V 130;130;119;119 136;136;125;125 RT;RT 44;67 65;69 11559430 Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine. In a subsequent sample 3 months later additional RT mutations were found, including A62V, Y188L, and Q151M, conferring high-level cross-resistance to multiple nucleoside analogs. 2001 AIDS research and human retroviruses Abstract HIV A62V;Q151M;Y188L 84;101;90 88;106;95 RT 49 51 11561722 Binding aspects of baicalein to HIV-1 integrase. In order to know the interaction mode of HIV-1 integrase with its inhibitor, we investigated the effect of the inhibitor, baicalein, on the conformation of the HIV-1 integrase catalytic domain [IN-(50-212/F185K)] using fluorescence and circular dichroism (CD) spectroscopy. 2001 Molecules and cells Abstract HIV F185K 205 210 IN;IN;IN 47;166;194 56;175;196 11562951 Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples. Tenofovir is uniquely active against multinucleoside-resistant HIV expressing the Q151M mutation, but shows reduced susceptibility to the T69S insertion mutations. 2001 Nucleosides, nucleotides & nucleic acids Abstract HIV Q151M;T69S 82;138 87;142 11562951 Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples. The presence of the lamivudine-associated M184V RT mutation increases tenofovir susceptibility in multiple HIV genotypes. 2001 Nucleosides, nucleotides & nucleic acids Abstract HIV M184V 42 47 RT 48 50 11563052 Understanding the mode of action of L-nucleosides as antiviral agents: a molecular modeling approach. Additionally, clinically important M184V mutation, which confers the viral resistance against 3TC and FTC, were studied by the same modeling system. 2001 Nucleosides, nucleotides & nucleic acids Abstract HIV M184V 35 40 11563081 Tenofovir (PMPA) is less susceptible to pyrophosphorolysis and nucleotide-dependent chain-terminator removal than zidovudine or stavudine. Recombinant HIV-1 wild-type reverse transcriptase (RT) and a mutant RT enzyme containing the AZT/thymidine analog resistance mutations D67N/K70R/T215Y were analyzed for pyrophosphorolysis and nucleotide-dependent chain-terminator removal activities. 2001 Nucleosides, nucleotides & nucleic acids Abstract HIV D67N;K70R;T215Y 135;140;145 139;144;150 RT;RT;RT 28;51;68 49;53;70 11567084 A directed approach to improving the solubility of Moloney murine leukemia virus reverse transcriptase. An important consequence of the improved solubility of the L435K MMLV RT has been the ability to obtain diffraction quality crystals. 2001 Protein science Abstract HIV L435K 59 64 RT 70 72 11567084 A directed approach to improving the solubility of Moloney murine leukemia virus reverse transcriptase. We have introduced a single amino acid substitution in the connection domain of an N-terminally truncated MMLV RT (L435K) that significantly improves the solubility of the enzyme eliminating the need for nonionic detergents in buffering storage solutions. 2001 Protein science Abstract HIV L435K 115 120 RT 111 113 11572864 The stereoselective targeting of a specific enzyme-substrate complex is the molecular mechanism for the synergic inhibition of HIV-1 reverse transcriptase by (R)-(-)-PPO464: a novel generation of nonnucleoside inhibitors. Only one enantiomer, (R)-(-)-PPO464, displayed antiviral activity against both the wild type and the K103N mutant HIV-1 RT and was found to interact exclusively with the reaction intermediate formed by RT complexed with both the DNA and the nucleotide substrates. 2001 The Journal of biological chemistry Abstract HIV K103N 101 106 RT;RT 120;202 122;204 11575933 Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors. For nevirapine with the Tyr188Cys RT there is however a more substantial movement of the drug molecule. 2001 Journal of molecular biology Abstract HIV Y188C 24 33 RT 34 36 11575933 Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors. In the case of the second generation compounds efavirenz with Tyr181Cys RT and UC-781 with Tyr188Cys RT there are only small rearrangements of either inhibitor within the binding site compared to wild-type RT and also for the first generation compounds TNK-651, PETT-2 and nevirapine with Tyr181Cys RT. 2001 Journal of molecular biology Abstract HIV Y181C;Y181C;Y188C 62;289;91 71;298;100 RT;RT;RT;RT 72;101;206;299 74;103;208;301 11575933 Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors. The main contribution to drug resistance for Tyr181Cys and Tyr188Cys RT mutations is the loss of aromatic ring stacking interactions for first generation compounds, providing a simple explanation for the resilience of second generation NNRTIs, as such interactions make much less significant contribution to their binding. 2001 Journal of molecular biology Abstract HIV Y181C;Y188C 45;59 54;68 NNRTI;RT 236;69 242;71 11575933 Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors. These are Tyr181Cys RT (TNK-651) to 2.4 A, Tyr181Cys RT (efavirenz) to 2.6 A, Tyr181Cys RT (nevirapine) to 3.0 A, Tyr181Cys RT (PETT-2) to 3.0 A, Tyr188Cys RT (nevirapine) to 2.6 A, Tyr188Cys RT (UC-781) to 2.6 A and Tyr188Cys RT (unliganded) to 2.8 A resolution. 2001 Journal of molecular biology Abstract HIV Y181C;Y181C;Y181C;Y181C;Y188C;Y188C;Y188C 10;43;78;114;146;182;217 19;52;87;123;155;191;226 RT;RT;RT;RT;RT;RT;RT 20;53;88;124;156;192;227 22;55;90;126;158;194;229 11581417 Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India: identification of features that distinguish subtype C sequences in India from other subtype C sequences. Of the three positions identified as signature amino acid substitution sites for C(IN) sequences (K340E, K350A, and G429E), 56% of the C(IN) sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. 2001 Journal of virology Abstract HIV G429E;K340E;K350A 116;98;105 121;103;110 IN;IN 83;137 85;139 11588503 Transient relapses ("blips") of plasma HIV RNA levels during HAART are associated with drug resistance. Mutations in the RT and protease gene conferring resistance to one or more drugs were observed in 8 of 11 patients, 6 of whom had the M184V substitution. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 134 139 PR;RT 24;17 32;19 11588509 HIV-1 induction-maintenance at the lymph node level: the "Apollo-97" Study. In the patient with stable lymph node viral RNA, selection of the M184V mutation was demonstrated at this level before detection in plasma and low blood saquinavir levels were found throughout the study. 2001 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 66 71 11591519 Simplified catechin-gallate inhibitors of HIV-1 reverse transcriptase. Systematic simplification of the molecular structures of epicatechin gallate and epigallocatechin gallate to determine the minimum structural characteristics necessary for HIV-1 reverse transcriptase inhibition in vitro resulted in several compounds that strongly inhibited the native as well as the A17 double mutant (K103N Y181C) enzyme, which is normally insensitive to most known nonnucleoside inhibitors. 2001 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 319;325 325;330 RT 178 199 11595597 Sexual transmission of HIV-1 isolate showing G-->A hypermutation. The patient's viral genotype showed several mutations related to antiretroviral drug resistance in RT (T69N, M184V, T215F, K219Q) and protease (M36I, G48V, I54V, T63L, V82A) genes. 2002 Journal of clinical virology Abstract HIV G48V;I54V;K219Q;M184V;M36I;T215F;T63L;T69N;V82A 150;156;123;109;144;116;162;103;168 154;160;128;114;148;121;166;107;172 PR;RT 134;99 142;101 11596076 Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen. All patients failing an efavirenz regimen harboured mutations conferring cross-resistance to nevirapine (K103N, Y188L, G190S). 2001 Journal of medical virology Abstract HIV G190S;K103N;Y188L 119;105;112 124;110;117 11596076 Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen. Among patients failing the nevirapine regimen and presenting with NNRTI mutations, 35 (80%) harboured mutations conferring cross-resistance to efavirenz (K101E, K103N, Y188L) and 9 (20%) harboured mutations conferring resistance to nevirapine alone (V106A and Y181C). 2001 Journal of medical virology Abstract HIV K101E;K103N;V106A;Y181C;Y188L 154;161;250;260;168 159;166;256;265;173 NNRTI 66 71 11597403 Antiviral drug design: computational analyses of the effects of the L100I mutation for HIV-RT on the binding of NNRTIs. Monte Carlo/free energy perturbation (MC/FEP) calculations were used to evaluate the binding free energy change for HIV-RT/inhibitor complexes upon L100I mutation. 2001 Bioorganic & medicinal chemistry letters Abstract HIV L100I 148 153 RT 120 122 11598128 Folded monomer of HIV-1 protease. Based on the crystal structure and our NMR results, we postulate that loss of specific interactions involving the side chain of Arg(87) destabilizes PR(R87K) by perturbing the inner C-terminal beta-sheet (residues 96-99 from each monomer), a region that is sandwiched between the two beta-strands formed by the N-terminal residues (residues 1-4) in the mature protease. 2001 The Journal of biological chemistry Abstract HIV R87K 152 156 PR;PR 360;149 368;151 11598128 Folded monomer of HIV-1 protease. However, binding of the inhibitor DMP323 to PR(R87K) produces a stable dimer complex. 2001 The Journal of biological chemistry Abstract HIV R87K 47 51 PR 44 46 11598128 Folded monomer of HIV-1 protease. We now show by NMR and sedimentation equilibrium studies that a mutant protease containing the R87K substitution (PR(R87K)) within the highly conserved Gly(86)-Arg(87)-Asn(88) sequence forms a monomer with a fold similar to a single subunit of the dimer. 2001 The Journal of biological chemistry Abstract HIV R87K;R87K 95;117 99;121 PR;PR 71;114 79;116 11600351 DPC 681 and DPC 684: potent, selective inhibitors of human immunodeficiency virus protease active against clinically relevant mutant variants. DPC 681 and DPC 684 showed no loss in potency toward recombinant mutant HIVs with the D30N mutation and a fivefold or smaller loss in potency toward mutant variants with three to five amino acid substitutions. 2001 Antimicrobial agents and chemotherapy Abstract HIV D30N 86 90 11600822 Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). K103N was the most common mutation detected. 2001 AIDS (London, England) Abstract HIV K103N 0 5 11600822 Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). The most common NVP(R) mutation detected in infants was Y181C. 2001 AIDS (London, England) Abstract HIV Y181C 56 61 11602042 Emergence of drug resistance mutations in a group of HIV-infected children taking nelfinavir-containing regimens. In three patients, the only new mutation after failure was the RT mutation M184V. 2001 AIDS research and human retroviruses Abstract HIV M184V 75 80 RT 63 65 11602042 Emergence of drug resistance mutations in a group of HIV-infected children taking nelfinavir-containing regimens. PI resistance mutations occurred in eight patients: D30N in six, and L90M in three. 2001 AIDS research and human retroviruses Abstract HIV D30N;L90M 52;69 56;73 PI 0 2 11602754 Structural and functional analysis of interhelical interactions in the human immunodeficiency virus type 1 gp41 envelope glycoprotein by alanine-scanning mutagenesis. Whereas alanine mutations at Leu-565 and Val-570 destabilized the trimer-of-hairpins structure, mutations at Gly-572 and Arg-579 led to the formation of a stable gp41 core. 2001 Journal of virology Abstract HIV A565L 8 36 gp41 162 166 11678470 The emergence and epidemiology of resistance in the nucleoside-experienced HIV-infected population. Nucleoside reverse transcriptase inhibitor-associated mutations form the majority of these, and the long and almost universal use of zidovudine and stavudine has led to mutations selected by these drugs being the most common observed, along with the primary lamivudine resistance mutation M184V. 2001 Antiviral therapy Abstract HIV M184V 289 294 NRTI 0 32 11678471 Mutational patterns in the HIV genome and cross-resistance following nucleoside and nucleotide analogue drug exposure. Other key mutations generally confer more limited resistance to specific agents, although the primary lamivudine- and abacavir-associated M184V substitution generates a broad spectrum of drug-dependent phenotypes, and uncommon mutational complexes conferring resistance across the entire class are well known. 2001 Antiviral therapy Abstract HIV M184V 138 143 11678471 Mutational patterns in the HIV genome and cross-resistance following nucleoside and nucleotide analogue drug exposure. These six mutations (M41L, D67N, K70R, L210W, T215Y/F, K219Q) enhance RT pyrophosphorolysis to confer high-level viral resistance to zidovudine, and clinically significant loss of response to stavudine and didanosine. 2001 Antiviral therapy Abstract HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 27;55;33;39;21;46;46 31;60;37;44;25;53;53 RT 70 72 11679914 Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. A P272S mutation occurred at high frequency in the viruses containing M184V, which did not revert. 2001 The Journal of infectious diseases Abstract HIV M184V;P272S 70;2 75;7 11679914 Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. Five of the infected monkeys maintained high virus loads; the sixth, which was infected with the E89G mutant strain, maintained viremia at a level below the limit of detection. 2001 The Journal of infectious diseases Abstract HIV E89G 97 101 11679914 Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. Sequence analysis demonstrated substantial reversion of the E89G mutation in the animals with progressive infection and preservation of this mutation in the animal with controlled infection. 2001 The Journal of infectious diseases Abstract HIV E89G 60 64 11679914 Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. Six macaques were inoculated with wild-type or mutated derivatives (E89G or E89G and M184V) of simian immunodeficiency virus macaque (SIVmac) 239. 2001 The Journal of infectious diseases Abstract HIV E89G;E89G;M184V 68;76;85 73;80;90 11679914 Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in Rhesus monkeys. These results demonstrate that the E89G mutation has a significant negative impact on SIVmac fitness, whereas SIVmac bearing M184V achieved high, sustained virus loads, perhaps with a compensatory effect of the P272S mutation. 2001 The Journal of infectious diseases Abstract HIV E89G;M184V;P272S 35;125;211 39;130;216 11684697 Mutational analysis of Tyr-501 of HIV-1 reverse transcriptase. Effects on ribonuclease H activity and inhibition of this activity by N-acylhydrazones. However, three mutants, Y501F, Y501W, and Y501R, possessed RNase H activities comparable with wild-type enzyme. 2002 The Journal of biological chemistry Abstract HIV Y501F;Y501R;Y501W 24;42;31 29;47;36 11684697 Mutational analysis of Tyr-501 of HIV-1 reverse transcriptase. Effects on ribonuclease H activity and inhibition of this activity by N-acylhydrazones. Importantly, BBNH was an effective inhibitor of the DNA polymerase activity of all Y501X mutants tested. 2002 The Journal of biological chemistry Abstract HIV Y501X 83 88 Pol 56 66 11684697 Mutational analysis of Tyr-501 of HIV-1 reverse transcriptase. Effects on ribonuclease H activity and inhibition of this activity by N-acylhydrazones. The replication "fitness" of HIV molecular clones with the Y501W or Y510R mutation was significantly compromised compared with wild-type virus. 2002 The Journal of biological chemistry Abstract HIV Y501W;Y510R 59;68 64;73 11684697 Mutational analysis of Tyr-501 of HIV-1 reverse transcriptase. Effects on ribonuclease H activity and inhibition of this activity by N-acylhydrazones. Whereas BBNH inhibited Y501F RT RNase H activity with potency equivalent to wild-type RT, the Y501W mutant showed a 6-fold resistance to inhibition by BBNH, and the Y501R mutant was completely resistant to inhibition by BBNH. 2002 The Journal of biological chemistry Abstract HIV Y501F;Y501R;Y501W 23;165;94 28;170;99 RT;RT 29;86 31;88 11689043 A leucine zipper motif in the cytoplasmic domain of gp41 is required for HIV-1 replication and pathogenesis in vivo. Although the infectivity of wild-type virions and that of L95R mutant virions were equally sensitive to heat treatment, we found that L95R produced more defective virions, due to reduced surface expression and virion incorporation of the env glycoprotein. 2001 Virology Abstract HIV L95R;L95R 58;134 62;138 Env 238 241 11689043 A leucine zipper motif in the cytoplasmic domain of gp41 is required for HIV-1 replication and pathogenesis in vivo. However, L95R replication was impaired in SupT1 cells and in the SCID-hu Thy/Liv mouse. 2001 Virology Abstract HIV L95R 9 13 11689043 A leucine zipper motif in the cytoplasmic domain of gp41 is required for HIV-1 replication and pathogenesis in vivo. The L95R mutant replicated to wild-type levels in activated peripheral blood mononuclear cells and CEMx174 cells. 2001 Virology Abstract HIV L95R 4 8 11689043 A leucine zipper motif in the cytoplasmic domain of gp41 is required for HIV-1 replication and pathogenesis in vivo. The second leucine residue of the leucine zipper was mutated (L95R) to determine the role of this motif in HIV-1 replication and pathogenesis. 2001 Virology Abstract HIV L95R 62 66 11689617 Moloney murine leukemia virus integrase protein augments viral DNA synthesis in infected cells. The DNA synthesis defect was rescued by complementing the Delta34 and DeltaIN mutants in trans with either wild-type IN or the D184A mutant IN, provided as a Gag-IN fusion protein. 2001 Journal of virology Abstract HIV D184A 127 132 Gag;IN;IN;IN 158;117;140;162 161;119;142;164 11689617 Moloney murine leukemia virus integrase protein augments viral DNA synthesis in infected cells. Using an MLV vector containing green fluorescent protein as a sensitive reporter for virus infection, we found that mutations in either the catalytic triad (D184A) or the HHCC motif (H61A) reduced infectivity by approximately 1,000-fold. 2001 Journal of virology Abstract HIV D184A;H61A 157;183 162;187 11689617 Moloney murine leukemia virus integrase protein augments viral DNA synthesis in infected cells. Using semiquantitative PCR to analyze viral cDNA synthesis in infected cells, we found the Delta34 and DeltaIN mutants to be markedly impaired while the D184A and H61A mutants synthesized cDNA at levels similar to the wild type. 2001 Journal of virology Abstract HIV D184A;H61A 153;163 158;167 11698656 Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons. Through surveillance of drug-resistant HIV-1 in 603 treatment-naive, recently diagnosed HIV-1-infected persons, we identified a distinct group of viruses that have mutations at codon 215 of the reverse transcriptase (RT) gene that are different from either the wild-type (WT) T or the zidovudine (AZT)-selected T215Y/F. 2001 Proc Natl Acad Sci U S A Abstract HIV T215F;T215Y 311;311 318;318 RT;RT 194;217 215;219 HIV infections 88 102 11700580 Human immunodeficiency virus type 1 hypersusceptibility to amprenavir in vitro can be associated with virus load response to treatment in vivo. The human immunodeficiency virus type 1 protease mutation N88S, which is occasionally selected by treatment with nelfinavir or indinavir, confers hypersusceptibility to amprenavir in vitro. 2001 Clinical infectious diseases Abstract HIV N88S 58 62 PR 40 48 11700580 Human immunodeficiency virus type 1 hypersusceptibility to amprenavir in vitro can be associated with virus load response to treatment in vivo. We report a case of N88S developing after virologic failure of both indinavir- and nelfinavir-containing regimens that was managed successfully with a regimen that contained amprenavir. 2001 Clinical infectious diseases Abstract HIV N88S 20 24 11708913 The biological effects of structural variation at the meta position of the aromatic rings and at the end of the alkenyl chain in the alkenyldiarylmethane series of non-nucleoside reverse transcriptase inhibitors. Additionally, ADAMs 19 (44-fold) and 21 (29-fold) were more effective against the A98G mutation (found in association with nevirapine resistance in vitro), and ADAM 21 was 5-fold and 2-fold more potent against the Y181C inactivation mutation than the previously reported ADAMs 15 and 17, respectively. 2001 Journal of medicinal chemistry Abstract HIV A98G;Y181C 82;214 86;219 11708913 The biological effects of structural variation at the meta position of the aromatic rings and at the end of the alkenyl chain in the alkenyldiarylmethane series of non-nucleoside reverse transcriptase inhibitors. Subsequent assessment against a panel of site-directed reverse transcriptase mutants in NL4-3 demonstrated no effect of the K103N mutation on antiviral efficacy and a slight enhancement (6- to 11-fold) in sensitivity to AZT-resistant viruses. 2001 Journal of medicinal chemistry Abstract HIV K103N 124 129 RT 55 76 11708913 The biological effects of structural variation at the meta position of the aromatic rings and at the end of the alkenyl chain in the alkenyldiarylmethane series of non-nucleoside reverse transcriptase inhibitors. Thus, we have identified a novel series of reverse transcriptase inhibitors with a favorable profile of antiviral activity against the primary mutation involved in clinical failure of non-nucleoside reverse transcriptase inhibitors, K103N, and that retain activity against a multidrug-resistant virus. 2001 Journal of medicinal chemistry Abstract HIV K103N 233 238 NNRTI;RT 184;43 220;64 11709099 Phylogenetic analysis of reverse transcriptase in antiretroviral drug-naive Korean HIV type 1 patients. Only one patient harbored variant virus containing a V179D mutation causing resistance to efavirenz. 2001 AIDS research and human retroviruses Abstract HIV V179D 53 58 11711607 Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. A double mutant (L234A, L235A) did not bind either FcgammaR or C1q, and both ADCC and CDC functions were abolished. 2001 Journal of virology Abstract HIV L234A;L235A 17;24 22;29 11711607 Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. K322A showed a twofold reduction in FcgammaR binding affinity and ADCC, while C1q binding and CDC were abolished. 2001 Journal of virology Abstract HIV K322A 0 5 11711607 Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. The b12 mutants K322A and L234A, L235A are useful tools for dissecting the in vivo roles of ADCC and CDC in the anti-HIV-1 activity of neutralizing antibodies. 2001 Journal of virology Abstract HIV K322A;L234A;L235A 16;26;33 21;31;38 11711617 Adaptive mutations in the V3 loop of gp120 enhance fusogenicity of human immunodeficiency virus type 1 and enable use of a CCR5 coreceptor that lacks the amino-terminal sulfated region. In contrast, V3 loop mutation N300Y was selected during virus replication in cells that contained only a trace of CCR5(Y14N) and this mutation increased the apparent affinity of the virus for this coreceptor, as indicated by a shift in the sigmoid-shaped infectivity curve toward lower concentrations. 2001 Journal of virology Abstract HIV N300Y 30 35 11711617 Adaptive mutations in the V3 loop of gp120 enhance fusogenicity of human immunodeficiency virus type 1 and enable use of a CCR5 coreceptor that lacks the amino-terminal sulfated region. Surprisingly, N300Y increased viral affinity for the second extracellular loop of CCR5(Y14N) rather than for the mutated amino terminus. 2001 Journal of virology Abstract HIV N300Y 14 19 11717806 DPC-083. DuPont Pharmaceuticals. DPC-083 and DPC-961 possess antiviral activity against mutant variants of HIV-1, including the K103N mutant, and have the same potency as efavirenz against wild-type virus in rhesus monkeys [312865]. 2001 Current opinion in investigational drugs (London, England Abstract HIV K103N 95 100 11724274 Genotypic and phenotypic evidence of different drug-resistance mutation patterns between B and non-B subtype isolates of human immunodeficiency virus type 1 found in Brazilian patients failing HAART. A strong cross-resistance phenotype among all four PI was associated with the mutation L90M in the subtype-B isolates, and with G48V and V82A/F in the non-B counterparts. 2001 Virus genes Abstract HIV G48V;L90M;V82A;V82F 128;87;137;137 132;91;143;143 PI 51 53 11724274 Genotypic and phenotypic evidence of different drug-resistance mutation patterns between B and non-B subtype isolates of human immunodeficiency virus type 1 found in Brazilian patients failing HAART. Although all patients were treated with similar P1 drug regimen, the non-B subtype isolates did not present the L90M and 184V mutations and used mainly G48V and V82A/F to achieve drug resistance. 2001 Virus genes Abstract HIV G48V;L90M;V82A;V82F 152;112;161;161 156;116;167;167 11734627 The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012. Here, we identify a single amino acid change (T198P) in gp120 that alters the neutralization sensitivity of the primary isolate DH012 to antibodies against multiple neutralization epitopes that include the V3, CD4-induced, and CD4 binding sites in gp120. 2001 Proc Natl Acad Sci U S A Abstract HIV T198P 46 51 gp120;gp120 56;248 61;253 11734627 The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012. The single amino acid mutation T198P in the beta3 severely compromises the interaction between the V1/V2 and V3 loops. 2001 Proc Natl Acad Sci U S A Abstract HIV T198P 31 36 11737372 MIKADO: a multicentre, open-label pilot study to evaluate the antiretroviral activity and safety of saquinavir with stavudine and zalcitabine. The only mutations detected were L90M substitutions in two patients. 2001 HIV medicine Abstract HIV L90M 33 37 11737373 Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48-week data from a randomized, double-blind trial. In the ABC + CART group, 16/25 (64%) patients with the M184V mutation at baseline had < or = 400 copies/mL or a decrease > or = 1 log10 copies/mL at week 16. 2001 HIV medicine Abstract HIV M184V 55 60 11737373 Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48-week data from a randomized, double-blind trial. The presence of M184V at baseline had minimal impact on the efficacy of ABC. 2001 HIV medicine Abstract HIV M184V 16 21 11737402 Phenotypic and genotypic resistance to nucleoside reverse transcriptase inhibitors in HIV-1 clinical isolates. At time 1, genotypic resistance to zidovudine was found in all cases (41L: four cases; 41L, 215Y: five cases; 41L, 210W, 215Y: two cases; K70R: one case) with a mean 6.6 +/- 1.6-fold increase in the median inhibitory concentration (IC50) to zidovudine and 1.7 +/- 0.4-fold to stavudine. 2001 HIV medicine Abstract HIV K70R 138 142 11737402 Phenotypic and genotypic resistance to nucleoside reverse transcriptase inhibitors in HIV-1 clinical isolates. At time 2, genotypic resistance to zidovudine was found in 11 out of 12 cases (41L: two cases; 41L, 215Y: six cases; 41L, 210W, 215Y: two cases; M41L, D67N, L210W, T215Y: one case) with a mean 18.9 +/- 8.8-fold increase in the IC50 to zidovudine and 1.4 +/- 0.4-fold to stavudine CONCLUSIONS: In this clinical series of patients with suboptimal control of plasma HIV-1 RNA using a combination including zidovudine, the presence of zidovudine-related mutations was associated with a decreased phenotypic sensitivity to this drug. 2001 HIV medicine Abstract HIV D67N;L210W;M41L;T215Y 151;157;145;164 155;162;149;169 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. In particular, two mutations (K70R and V118I), detectable by LIPA and by sequencing analysis respectively, revealed resistance to NRTIs in two plasma samples. 2001 BMC microbiology Abstract HIV K70R;V118I 30;39 35;44 NRTI 130 135 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. Remarkably, a key mutation, like V82A (found as a mixture), and some "indeterminate" results (9 samples), due the absence of signal on the lines corresponding to a specific probe, was revealed only by LIPA, while a variable number of secondary mutations was detectable only by TruGene HIV-1 assay. 2001 BMC microbiology Abstract HIV V82A 33 37 11738338 Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a cohort of Italian HIV-1 seropositive patients extensively treated with antiretroviral drugs. Results showed the presence of one or more mutations (A62V, V75I, F77L, F116Y and Q151M) able to confer resistance to all NRTIs in a relatively high percentage (7.9%) of patients enrolled in the study. 2001 International journal of antimicrobial agents Abstract HIV A62V;F116Y;F77L;Q151M;V75I 54;72;66;82;60 58;77;70;87;64 NRTI 122 127 11741162 Plasma drug levels, genotypic resistance, and virological response to a nelfinavir plus saquinavir-containing regimen. A higher number of mutations in the protease gene (12 versus 8;P = 0.001), and the L90M mutation (36% versus 67%; P = 0.001) were associated with treatment failure. 2002 AIDS (London, England) Abstract HIV L90M 83 87 PR 36 44 11741169 Use of the sensitive/less-sensitive (detuned) EIA strategy for targeting genetic analysis of HIV-1 to recently infected blood donors. Genetic evidence for drug resistance to zidovudine (K70R) and non-nucleoside analog reverse transcriptase inhibitors (V108I) was detected in one strain each, and three other strains showed the presence of accessory protease inhibitor resistance mutations. 2002 AIDS (London, England) Abstract HIV K70R;V108I 52;118 56;123 RT;PR 84;215 105;223 11741936 Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of a high multitude of HIV-1 resistance against protease inhibitors. In this study we identified multiple novel amino acid substitutions including L75R, H219Q, V390D/V390A, R409K, and E468K in the Gag protein at non-cleavage sites in common among HIV-1 variants selected against the following four PIs: amprenavir, JE-2147, KNI-272, and UIC-94003. 2002 The Journal of biological chemistry Abstract HIV E468K;H219Q;L75R;R409K;V390A;V390D 115;84;78;104;91;91 120;89;82;109;96;96 Gag;PI 128;229 131;232 11742431 Baseline antiretroviral drug susceptibility influences treatment response in patients receiving saquinavir-enhancing therapy. Genotypic resistance to SQV was defined by the presence of G48V and/or L90M mutations in the protease gene. 2001 HIV clinical trials Abstract HIV G48V;L90M 59;71 63;75 PR 93 101 11745924 Failure of stavudine-lamivudine combination therapy in antiretroviral-naive patients with AZT-like HIV-1 resistance mutations. The genotypic pattern of the latter two isolates showed the combined mutations M184V plus R211K and L214F. 2001 Journal of medical virology Abstract HIV L214F;M184V;R211K 100;79;90 105;84;95 11748652 In vivo HIV-1 compartmentalisation: drug resistance-associated mutation distribution. However, some mutations detectable in some tissues were not seen in plasma (e.g., M46I and D30N in the protease). 2002 Journal of medical virology Abstract HIV D30N;M46I 91;82 95;86 PR 103 111 11752705 In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants. Fitness determination of single mutants confirmed that, in the presence of nevirapine, every variant was more fit than wild-type with a fitness order Y181C>V106A>G190A>wild-type. 2002 The Journal of general virology Abstract HIV G190A;V106A;Y181C 162;156;150 167;161;155 11752705 In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants. In passage 5, mutations V106A, Y181C and G190A were detected in the global population, associated with a 100-fold susceptibility decrease. 2002 The Journal of general virology Abstract HIV G190A;V106A;Y181C 41;24;31 46;29;36 11752705 In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants. Unexpectedly, in the absence of the drug, the Y181C resistant mutant was more fit than wild-type, with a fitness gradient Y181C>wild-type >G106A>or=V190A. 2002 The Journal of general virology Abstract HIV G106A;V190A;Y181C;Y181C 139;148;46;122 144;153;51;127 11752705 In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants. Using a molecular clone in which the Y181C mutation was introduced by in vitro mutagenesis, the greater fitness of the Y181C mutant was confirmed in new competition cultures. 2002 The Journal of general virology Abstract HIV Y181C;Y181C 37;119 42;124 11771730 Stereochemistry as a major determinant of the anti-HIV activity of chiral naphthyl thiourea compounds. All five 'R' stereoisomers were active anti-HIV agents and inhibited the replication of the HIV-1 strains HTLV-IIIB (NNI-sensitive), A17 (NNI-resistant, Y181C mutant RT) and A17Var (NNI-resistant, Y181C plus K103N mutant RT), as well as primary HIV-1 isolates from AIDS patients in human PBMC at nanomolar concentrations, whereas their enantiomers were inactive. 2001 Antiviral chemistry & chemotherapy Abstract HIV K103N;Y181C;Y181C 208;153;197 213;158;202 RT;RT 166;221 168;223 AIDS 265 269 11773409 A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site. Upon selection of HIV-1 in the presence of UIC-94003, mutants carrying a novel active-site mutation, A28S, in the presence of L10F, M46I, I50V, A71V, and N88D appeared. 2002 Journal of virology Abstract HIV A28S;A71V;I50V;L10F;M46I;N88D 101;144;138;126;132;154 105;148;142;130;136;158 11782585 Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails. Similar analysis showed that recombinant viruses harboring mutations known to confer resistance to NRTIs (zidovudine, lamivudine, and abacavir) and NNRTIs (efavirenz and nevirapine) as well as the multidrug resistance-associated mutation Q151M and double codon insertions (SS and SG) were also susceptible to inhibition by DXG. 2002 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 238 243 NNRTI;NRTI 148;99 154;104 11782585 Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails. The L74V mutant remained susceptible to inhibition by DXG, and the K65R mutant demonstrated moderate resistance to DXG. 2002 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;L74V 67;4 71;8 11782585 Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails. We also examined site-directed mutants containing only L74V or K65R, the characteristic resistance mutations for DXG. 2002 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;L74V 63;55 67;59 11790852 Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease. The three-dimensional structures of indinavir and three newly synthesized indinavir analogs in complex with a multi-drug-resistant variant (L63P, V82T, I84V) of HIV-1 protease were determined to approximately 2.2 A resolution. 2002 Protein science Abstract HIV I84V;L63P;V82T 152;140;146 156;144;150 PR 167 175 11793380 Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. A relationship was found between the E44D/A and/or V118I mutational pattern and experience with didanosine or stavudine but not with lamivudine. 2002 Journal of medical virology Abstract HIV E44A;E44D;V118I 37;37;51 43;43;56 11793380 Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. It has been reported that a new pattern of mutations, E44D/A and/or V118I, in the reverse transcriptase (RT) gene of HIV-1 confers a moderate level of resistance to lamivudine in the absence of the M184V mutation. 2002 Journal of medical virology Abstract HIV E44A;E44D;M184V;V118I 54;54;198;68 60;60;203;73 RT;RT 82;105 103;107 11793380 Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. Multivariate analysis showed an association between the E44D/A and/or V118I mutational pattern and the RT mutations D67N, T69D, L210W, and T215Y/F. 2002 Journal of medical virology Abstract HIV D67N;E44A;E44D;L210W;T215F;T215Y;T69D;V118I 116;56;56;128;139;139;122;70 120;62;62;133;146;146;126;75 RT 103 105 11793380 Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. Mutation at codon 44 was identified in 41 patients (7 mutations E44A and 34 mutations E44D), mutation V118I was identified in 73 patients and a combination of mutations at codons 44 and 118 was found in 32 patients. 2002 Journal of medical virology Abstract HIV E44A;E44D;V118I 64;86;102 68;90;107 11793380 Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. No relationship was observed between this mutational pattern and the lamivudine-specific resistance mutation M184V. 2002 Journal of medical virology Abstract HIV M184V 109 114 11793380 Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. The results suggest that the development of the E44D/A and/or V118I mutational pattern is frequent in patients treated with NRTIs. 2002 Journal of medical virology Abstract HIV E44A;E44D;V118I 48;48;62 54;54;67 NRTI 124 129 11799170 Persistence and fitness of multidrug-resistant human immunodeficiency virus type 1 acquired in primary infection. In two of these PHI cases, a rebound to higher levels of plasma viremia only occurred when the M184V mutation in reverse transcriptase could no longer be detected and, in a third case, nondetection of M184V was associated with an inability to isolate virus. 2002 Journal of virology Abstract HIV M184V;M184V 95;201 100;206 RT 113 134 HIV infections 16 19 11805439 Prevalence and genetic heterogeneity of the reverse transcriptase T69S-S-X insertion in pretreated HIV-infected patients. It was always found coupled to the T69S mutation. 2001 Intervirology Abstract HIV T69S 35 39 11808752 Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy. A recent genotypic study in naive patients receiving stavudine/didanosine combination showed emergence of TAMs and a multidrug-resistance mutation (MDR), Q151M, in 36 and 10% of cases, respectively. 2001 Antiviral therapy Abstract HIV Q151M 154 159 11808752 Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy. CONCLUSIONS: Our study clearly demonstrated that naive subjects treated with stavudine/lamivudine for 24-48 weeks selected a low rate of TAMs and MDR Q151M. 2001 Antiviral therapy Abstract HIV Q151M 150 155 11808752 Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy. One hypothesis explaining these results could be the development of the M184V mutation. 2001 Antiviral therapy Abstract HIV M184V 72 77 11808752 Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy. Only two subjects (4.5%) developed a TAM (T215Y; M41L), one subject developed a V75T/A mutation and one subject developed the particular MDR pattern F116Y, Q151M. 2001 Antiviral therapy Abstract HIV F116Y;M41L;Q151M;T215Y;V75A;V75T 149;49;156;42;80;80 154;53;161;47;86;86 11808752 Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy. RESULTS: At the end of the follow-up, all patients acquired the lamivudine-associated mutation M184V. 2001 Antiviral therapy Abstract HIV M184V 95 100 11812826 A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. A compensatory mutation (M230I) in the primer grip of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) restores the replication capacity of virus having a Y115W mutation in their RT coding region. 2001 Nucleic acids research Abstract HIV M230I;Y115W 25;177 30;182 RT;RT;RT 98;121;201 119;123;203 11812826 A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. Gel-based fidelity assays with the double mutant Y115W/M230I revealed that the M230I substitution increased the accuracy of mutant Y115W. 2001 Nucleic acids research Abstract HIV M230I;M230I;Y115W;Y115W 55;79;49;131 60;84;54;136 11812826 A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. However, when present alone, M230I conferred reduced fidelity as determined in misinsertion and mispair extension fidelity assays, as well as in primer extension assays carried out with three dNTPs. 2001 Nucleic acids research Abstract HIV M230I 29 34 11812826 A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. The mutant M230I showed a 3.3-16-fold increase in misinsertion efficiency for G, C and T opposite T, compared with the wild-type enzyme. 2001 Nucleic acids research Abstract HIV M230I 11 16 11812826 A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. The Y115W substitution impairs DNA polymerase activity and produces an enzyme with a lower fidelity of DNA synthesis. 2001 Nucleic acids research Abstract HIV Y115W 4 9 Pol 35 45 11812826 A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. Unlike wild-type HIV-1 RT, nucleotide selectivity of mutant M230I at dT:dG, dT:dC and dT:dT mispairs was almost exclusively dependent on the K(m) values for correct and incorrect dNTPs, a characteristic that has not been described for other low fidelity mutants of HIV-1 RT. 2001 Nucleic acids research Abstract HIV M230I 60 65 RT;RT 23;271 25;273 11812826 A mutation in the primer grip region of HIV-1 reverse transcriptase that confers reduced fidelity of DNA synthesis. Y115W/M230I showed wild-type misinsertion fidelity in assays performed with DNA/DNA templates. 2001 Nucleic acids research Abstract HIV M230I;Y115W 6;0 11;5 11819180 Efficacy and safety of stavudine plus didanosine in asymptomatic HIV-infected children with plasma HIV RNA below 50,000 copies per milliliter. However, four children developed AZT-like mutations T215Y and/or M41L. 2002 HIV clinical trials Abstract HIV M41L;T215Y 65;52 69;57 11819180 Efficacy and safety of stavudine plus didanosine in asymptomatic HIV-infected children with plasma HIV RNA below 50,000 copies per milliliter. Resistance mutations linked to didanosine (L74V or M184V) or stavudine (V75T) were not recognized and neither were multinucleoside resistant genotypes (151 complex or 69 inserts). 2002 HIV clinical trials Abstract HIV L74V;M184V;V75T 43;51;72 48;56;76 11825939 Discordance between genotypic and phenotypic drug resistance profiles in human immunodeficiency virus type 1 strains isolated from peripheral blood mononuclear cells. The most frequent resistance mutations were M184V (18 isolates) and M41L (7 isolates). 2002 Journal of clinical microbiology Abstract HIV M184V;M41L 44;68 49;72 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. Among patients with nelfinavir treatment failure, we found that D30N acquisition was strongly suppressed when L90M preexisted. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 64;110 68;114 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. However, their evolutionary pathways appeared to be highly complex and to still have something in common, as they always contained several additional polymorphisms, including L63P and N88D, as common signatures. 2002 Antimicrobial agents and chemotherapy Abstract HIV L63P;N88D 175;184 179;188 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. In contrast, D30N/L90M demonstrated severe impairment. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 13;18 17;22 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. In the disease course, the D30N and L90M clones readily evolved independently of each other, and later the D30N/L90M double mutants emerged. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;D30N;L90M;L90M 27;107;112;36 31;111;116;40 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. L90M caused little impairment of the cleavage activities, but D30N was detrimental, although significant residual activity was observed. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 62;0 66;4 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. Supporting this notion, the D30N/L90M mutation was also quite rare in a large clinical database. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 28;33 32;37 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. The double mutants appeared to originate from the D30N lineage but not from the L90M lineage, or were strongly associated with the former. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 50;80 54;84 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. These results suggest that D30N and L90M are mutually exclusive during the evolutionary process. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 27;36 31;40 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. Thus, D30N/L90M double mutations not only were detected in a very limited number of patients but also accounted for a minor fraction within each patient. 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 6;11 10;15 11850252 Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. We studied the evolutionary relationships between the two protease inhibitor (PI) resistance mutations, D30N and L90M, of human immunodeficiency virus type 1 (HIV-1). 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 104;113 108;117 PR;PI 58;78 66;80 11850255 Emergence of resistance to protease inhibitor amprenavir in human immunodeficiency virus type 1-infected patients: selection of four alternative viral protease genotypes and influence of viral susceptibility to coadministered reverse transcriptase nucleoside inhibitors. Previous data have indicated that the development of resistance to amprenavir, an inhibitor of the human immunodeficiency virus type 1 protease, is associated with the substitution of valine for isoleucine at residue 50 (I50V) in the viral protease. 2002 Antimicrobial agents and chemotherapy Abstract HIV I50V;I50V 221;184 225;219 PR;PR 135;240 143;248 11850255 Emergence of resistance to protease inhibitor amprenavir in human immunodeficiency virus type 1-infected patients: selection of four alternative viral protease genotypes and influence of viral susceptibility to coadministered reverse transcriptase nucleoside inhibitors. The I50V and I84V genotypes displayed the greatest reductions in susceptibility to amprenavir, although each of the amprenavir-selected genotypes conferred little or no cross-resistance to other protease inhibitors. 2002 Antimicrobial agents and chemotherapy Abstract HIV I50V;I84V 4;13 8;17 PR 195 203 11850255 Emergence of resistance to protease inhibitor amprenavir in human immunodeficiency virus type 1-infected patients: selection of four alternative viral protease genotypes and influence of viral susceptibility to coadministered reverse transcriptase nucleoside inhibitors. These mutations fell into four distinct categories, characterized by the presence of either I50V, I54L/I54M, I84V, or V32I+I47V and often included accessory mutations, commonly M46I/L. 2002 Antimicrobial agents and chemotherapy Abstract HIV I47V;I50V;I54L;I54M;I84V;M46I;M46L;V32I 123;92;98;98;109;177;177;118 127;96;102;102;113;183;183;122 11865396 T69D/N pol mutation, human immunodeficiency virus type 1 RNA levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy. Disease progression was not associated with mutations in the reverse-transcriptase gene previously associated with resistance to ddI (L74V, K65R, or M184V). 2002 The Journal of infectious diseases Abstract HIV K65R;L74V;M184V 140;134;149 144;138;154 RT 61 82 11865396 T69D/N pol mutation, human immunodeficiency virus type 1 RNA levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy. The selection of the T69D/N mutation in children with HIV-1 disease progression during ddI therapy suggests that this mutation confers a fitness advantage to the virus that may include resistance to ddI. 2002 The Journal of infectious diseases Abstract HIV T69D;T69N 21;21 27;27 11865396 T69D/N pol mutation, human immunodeficiency virus type 1 RNA levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy. Three viral parameters, syncytium-inducing phenotype, higher virus load, and mutation in HIV-1 pol encoding the T69D/N mutation, were associated with disease progression. 2002 The Journal of infectious diseases Abstract HIV T69D;T69N 112;112 118;118 Pol 95 98 11873006 Low prevalence of primary mutations associated with drug resistance in antiviral-naive patients at therapy initiation. Among mutations associated with high-level resistance to RTI, T215Y was found in only two patients, M184V in two cases, T69D and T215C in other two cases (one each), and K103N in only one patient, for a total of six patients (one carrying both T215Y and M184V) (1.7%). 2002 AIDS (London, England) Abstract HIV K103N;M184V;M184V;T215C;T215Y;T215Y;T69D 170;100;254;129;62;244;120 175;105;259;134;67;249;124 RT 57 60 11873006 Low prevalence of primary mutations associated with drug resistance in antiviral-naive patients at therapy initiation. Primary mutations associated with substantial resistance to protease inhibitors were found in only five of 347 patients (1.4%) (M46V/L, I54V, V82A/I); all the other patients carried only secondary mutations (L10F/I/V, M36I, L63P, A71T/V, V77I). 2002 AIDS (London, England) Abstract HIV A71T;A71V;I54V;L10F;L10I;L10V;L63P;M36I;M46L;M46V;V77I;V82A;V82I 230;230;136;208;208;208;224;218;128;128;238;142;142 236;236;140;216;216;216;228;222;134;134;242;148;148 PR 60 68 11878404 HIV-1 reverse transcriptase mutations found in a drug-experienced patient confer reduced susceptibility to multiple nucleoside reverse transcriptase inhibitors. A chimeric virus, including the patient's RT sequence from codon 25 to codon 220, which carried the resistance mutations M41 L, D67N, T69D, K70R, L210W and T215Y in addition to V75M, displayed reduced susceptibility to multiple nucleoside RT inhibitors (NRTIs). 2001 Antiviral therapy Abstract HIV D67N;K70R;L210W;M41L;T215Y;T69D;V75M 128;140;146;121;156;134;177 132;144;151;126;161;138;181 NRTI;RT;RT 254;42;239 259;44;241 11878404 HIV-1 reverse transcriptase mutations found in a drug-experienced patient confer reduced susceptibility to multiple nucleoside reverse transcriptase inhibitors. One patient, treated with stavudine for 1 month and treated previously with zidovudine, zalcitabine and lamivudine, carried a mutation at codon 75 of the RT (V75M). 2001 Antiviral therapy Abstract HIV V75M 158 162 RT 154 156 11878404 HIV-1 reverse transcriptase mutations found in a drug-experienced patient confer reduced susceptibility to multiple nucleoside reverse transcriptase inhibitors. Removal of V75M from this RT background resulted in a return of susceptibility to didanosine and lamivudine. 2001 Antiviral therapy Abstract HIV V75M 11 15 RT 26 28 11882000 Structure-activity relationships of 2'-fluoro-2',3'-unsaturated D-nucleosides as anti-HIV-1 agents. The implications for drug resistance of the titled nucleosides with respect to lamivudine-resistant variants (M184V) were also examined, and no significant cross-resistance with the variants was observed with the D-series. 2002 Journal of medicinal chemistry Abstract HIV M184V 110 115 11882275 [Mutations of resistance of HIV-1 in previously untreated patients at penitentiary centers of the Autonomous Community of Valencia, Spain. REPRICOVA study]. With regard to NIRT, 7 samples (5.2% of total) showed some mutation of resistance: M41L, D67N, L210W and K219Q, all them secondary to and associated with resistance to zidovudine, abacavir as well as group B multinucleoside-resistance. 2002 Medicina clinica Abstract HIV D67N;K219Q;L210W;M41L 89;105;95;83 93;110;100;87 11882275 [Mutations of resistance of HIV-1 in previously untreated patients at penitentiary centers of the Autonomous Community of Valencia, Spain. REPRICOVA study]. With regard to PI, only one sample showed a primary mutation, M46I, which was associated with resistance to indinavir. 2002 Medicina clinica Abstract HIV M46I 62 66 PI 15 17 11884549 The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. Based on these results, and on the results of other excision experiments, we present a model to explain how the M184V mutation affects AZTMP excision. 2002 Journal of virology Abstract HIV M184V 112 117 11884549 The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. However, in the presence of ATP, the M184V mutation does decrease the ability of HIV-1 RT to carry out AZTMP excision. 2002 Journal of virology Abstract HIV M184V 37 42 RT 87 89 11884549 The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. The M184V mutation alters the polymerase active site in a fashion that specifically interferes with ATP-mediated excision of AZTMP from the end of the primer strand. 2002 Journal of virology Abstract HIV M184V 4 9 Pol 30 40 11884549 The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. The M184V mutation does not affect the incorporation of AZT 5'-triphosphate (AZTTP), either in the presence or the absence of mutations that enhance AZTMP excision. 2002 Journal of virology Abstract HIV M184V 4 9 11884549 The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. The M184V mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) causes resistance to lamivudine, but it also increases the sensitivity of the virus to zidovudine (3'-azido-3'-deoxythymidine; AZT). 2002 Journal of virology Abstract HIV M184V 4 9 RT;RT 66;89 87;91 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. In the present study we present structural observations from Efavirenz in complex with wild-type protein and the K103N mutant and PNU142721 and MSC194 in complex with the K103N mutant. 2002 European journal of biochemistry Abstract HIV K103N;K103N 113;171 118;176 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. Inhibitors with good activity against the K103N mutant would be expected to have favorable interactions with the mutant asparagines side chain, thereby compensating for resistance caused by stabilization of the mutant enzyme due to a hydrogen-bond network involving the N103 and Y188 side chains. 2002 European journal of biochemistry Abstract HIV K103N 42 47 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. The drugs Efavirenz, MSC194 and PNU142721 belong to the recent generation of NNRTIs characterized by an improved resistance profile to the most common single point mutations within HIV-1 RT, including the K103N mutation. 2002 European journal of biochemistry Abstract HIV K103N 205 210 NNRTI;RT 77;187 83;189 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. The K103N substitution is a frequently observed HIV-1 RT mutation in patients who do not respond to combination-therapy. 2002 European journal of biochemistry Abstract HIV K103N 4 9 RT 54 56 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. The structures unanimously indicate that the K103N substitution induces only minor positional adjustments of the three inhibitors and the residues lining the binding pocket. 2002 European journal of biochemistry Abstract HIV K103N 45 50 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. These potent inhibitors accommodate to the K103N mutation by forming new interactions to the N103 side chain. 2002 European journal of biochemistry Abstract HIV K103N 43 48 11895437 Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. This is supported by changes in hydrophobic and electrostatic interactions to the inhibitors between wild-type and K103N mutant complexes. 2002 European journal of biochemistry Abstract HIV K103N 115 120 11897594 Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy. Among 78 patients meeting study selection criteria, baseline primary PI resistance mutations included L90M (42% of patients), V82A/F/T (27%), D30N (21%), G48V (6%), and I84V (4%). 2002 Antimicrobial agents and chemotherapy Abstract HIV D30N;G48V;I84V;L90M;V82A;V82F;V82T 142;154;169;102;126;126;126 146;158;173;106;134;134;134 PI 69 71 11897594 Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy. D30N persisted less frequently than L90M (50% versus 100%, respectively; P < 0.001) and V82A/F/T (50% versus 81%, respectively; P = 0.05). 2002 Antimicrobial agents and chemotherapy Abstract HIV L90M;V82A;V82F;V82T;D30N 36;88;88;88;0 40;96;96;96;4 11897594 Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy. HIV-1 isolates from 38 (49%) patients failing PI salvage therapy developed new primary PI resistance mutations including L90M, I84V, V82A, and G48V. 2002 Antimicrobial agents and chemotherapy Abstract HIV G48V;I84V;L90M;V82A 143;127;121;133 147;131;125;137 PI;PI 46;87 48;89 11897594 Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy. The persistence of L90M, V82A/F/T, G48V, and I84V during salvage therapy suggests that these mutations play a role in clinical resistance to multiple PIs. 2002 Antimicrobial agents and chemotherapy Abstract HIV G48V;I84V;L90M;V82A;V82F;V82T 35;45;19;25;25;25 39;49;23;33;33;33 PI 150 153 11907245 Mutations that confer resistance to template-analog inhibitors of human immunodeficiency virus (HIV) type 1 reverse transcriptase lead to severe defects in HIV replication. The mutations associated, N255D or N265D, displayed low-level resistance to RT1t49, while high-level resistance could be observed when both mutations were present (Dbl). 2002 Journal of virology Abstract HIV N255D;N265D 26;35 31;40 11907381 Detection and quantification of multiple drug resistance mutations in HIV-1 reverse transcriptase by an oligonucleotide ligation assay. In one patient, the kinetics of the increase of MDR mutants could be followed in sequential samples, with K103N being detected earlier by OLA than by sequencing. 2001 Journal of human virology Abstract HIV K103N 106 111 11907381 Detection and quantification of multiple drug resistance mutations in HIV-1 reverse transcriptase by an oligonucleotide ligation assay. Q151M mutants were detected as minor populations (13%-24%) by OLA but not by sequencing in 4 samples. 2001 Journal of human virology Abstract HIV Q151M 0 5 11907381 Detection and quantification of multiple drug resistance mutations in HIV-1 reverse transcriptase by an oligonucleotide ligation assay. RESULTS: K103N mutants were detected as minor populations (5%-30%) by OLA in 6 of 18 samples from patients treated with nonnucleoside reverse transcription inhibitors and classified as wild type by sequencing. 2001 Journal of human virology Abstract HIV K103N 9 14 RT 134 155 11919491 Selection of drug-resistant HIV-1 mutants in response to repeated structured treatment interruptions. Longitudinal analysis of patient samples revealed a step-wise increase in the M184V mutation in each patient virus population over successive STIs, despite the lower replicative capacity associated with this mutation in the absence of antiviral agents. 2002 AIDS (London, England) Abstract HIV M184V 78 83 11919491 Selection of drug-resistant HIV-1 mutants in response to repeated structured treatment interruptions. RESULTS: Consistent with a loss of phenotypic susceptibility to lamivudine, the M184V mutation was detected by genotypic analysis (direct and clonal sequencing) in plasma samples collected from two patients at the end of the second or third STI. 2002 AIDS (London, England) Abstract HIV M184V 80 85 11920313 Broad nucleoside-analogue resistance implications for human immunodeficiency virus type 1 reverse-transcriptase mutations at codons 44 and 118. As expected, E44A/D and V118I mutations were strongly associated with M41L, D67N, L210W, and T215Y but also with other mutations, including K43E/N/Q, T69D, V75M, H208Y, R211K, and K219R. 2002 The Journal of infectious diseases Abstract HIV D67N;E44A;E44D;H208Y;K219R;K43E;K43N;K43Q;L210W;M41L;R211K;T215Y;T69D;V118I;V75M 76;13;13;162;180;140;140;140;82;70;169;93;150;24;156 80;19;19;167;185;148;148;148;87;74;174;98;154;29;160 11920313 Broad nucleoside-analogue resistance implications for human immunodeficiency virus type 1 reverse-transcriptase mutations at codons 44 and 118. Both E44D and V118I were more frequently associated with stavudine and didanosine than with zidovudine and lamivudine treatment. 2002 The Journal of infectious diseases Abstract HIV E44D;V118I 5;14 9;19 11920313 Broad nucleoside-analogue resistance implications for human immunodeficiency virus type 1 reverse-transcriptase mutations at codons 44 and 118. However, selection of E44A/D and V118I was also detected in association with a switch to other nucleoside RT inhibitors, including zalcitabine and abacavir. 2002 The Journal of infectious diseases Abstract HIV E44A;E44D;V118I 22;22;33 28;28;38 RT 106 108 11923351 Frequency of mutations conferring resistance to nucleoside reverse transcriptase inhibitors in human immunodeficiency virus type 1-infected patients in Korea. However, Q151M was not detected. 2002 Journal of clinical microbiology Abstract HIV Q151M 9 14 11923351 Frequency of mutations conferring resistance to nucleoside reverse transcriptase inhibitors in human immunodeficiency virus type 1-infected patients in Korea. In particular, the frequency of T69N/S/A increased sharply after more than 48 months of zidovudine monotherapy. 2002 Journal of clinical microbiology Abstract HIV T69A;T69N;T69S 32;32;32 40;40;40 11923351 Frequency of mutations conferring resistance to nucleoside reverse transcriptase inhibitors in human immunodeficiency virus type 1-infected patients in Korea. Mutations conferring resistance to didanosine and lamivudine were detected in 2 (L74V and M184I; 14.2%) of 11 patients tested and in 4 (M184V; 57%) of 7 patients tested, respectively. 2002 Journal of clinical microbiology Abstract HIV L74V;M184I;M184V 81;90;136 86;95;141 11923351 Frequency of mutations conferring resistance to nucleoside reverse transcriptase inhibitors in human immunodeficiency virus type 1-infected patients in Korea. The frequencies of K70R, T215S/Y/F (i.e., mutation of T at codon 215 to S, Y, or F), D67N/E, K219Q, T69N/S/A, M41L, and L210W mutations conferring resistance to zidovudine were 57.6, 36.4, 36.4, 27.2, 24.2, 21.2, and 12.1%, respectively. 2002 Journal of clinical microbiology Abstract HIV D67E;D67N;K219Q;K70R;L210W;M41L;T215F;T215S;T215Y;T69A;T69N;T69S 85;85;93;19;120;110;25;25;25;100;100;100 91;91;98;23;125;114;34;34;34;108;108;108 11923366 Rapid and sensitive oligonucleotide ligation assay for detection of mutations in human immunodeficiency virus type 1 associated with high-level resistance to protease inhibitors. Oligonucleotides were designed to detect primary mutations associated with high-level resistance to amprenavir, nelfinavir, indinavir, ritonavir, saquinavir, and lopinavir, including amino acid substitutions D30N, I50V, V82A/S/T, I84V, N88D, and L90M. 2002 Journal of clinical microbiology Abstract HIV D30N;I50V;I84V;L90M;N88D;V82A;V82S;V82T 208;214;230;246;236;220;220;220 212;218;234;250;240;228;228;228 11926830 The HIV-1 gp41 N-terminal heptad repeat plays an essential role in membrane fusion. Furthermore, a mutation in the NHR that renders the virus noninfectious is reflected by a significant reduction in in vitro lipid mixing induced by the mutant, gp41/1-70 (I62D). 2002 Biochemistry Abstract HIV I62D 171 175 gp41 160 164 11927582 Mechanistic role of residue Gln151 in error prone DNA synthesis by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. First, we found the binding affinity (K(D)) of wild type and Q151N RT proteins to different template/primers to be similar. 2002 The Journal of biological chemistry Abstract HIV Q151N 61 66 RT 67 69 11927582 Mechanistic role of residue Gln151 in error prone DNA synthesis by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. In contrast, the ability of the Q151N mutant to bind both correct and incorrect dNTPs (K(d)) was diminished. 2002 The Journal of biological chemistry Abstract HIV Q151N 32 37 11927582 Mechanistic role of residue Gln151 in error prone DNA synthesis by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. Presumably, the fidelity increase observed during the steady state is explained by this defect in Q151N binding to incorrect dNTP. 2002 The Journal of biological chemistry Abstract HIV Q151N 98 103 11927582 Mechanistic role of residue Gln151 in error prone DNA synthesis by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. Since the Q151N mutation also alters RT binding to correct dNTPs, the wild type Gln(151) residue may play an important role in efficient binding of RT to correct dNTPs. 2002 The Journal of biological chemistry Abstract HIV Q151N 10 15 RT;RT 37;148 39;150 11927582 Mechanistic role of residue Gln151 in error prone DNA synthesis by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. The Q151N mutant was 120-fold less efficient at binding correct dNTP than wild type RT, and its decrease in binding was such that we were unable to measure the actual binding affinity of Q151N for incorrect dNTPs. 2002 The Journal of biological chemistry Abstract HIV Q151N;Q151N 4;187 9;192 RT 84 86 11927582 Mechanistic role of residue Gln151 in error prone DNA synthesis by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Pre-steady state kinetic study of the Q151N HIV-1 RT mutant with increased fidelity. Using our Q151N high fidelity mutant, which is structurally altered in its ability to interact with the 3'-OH on the sugar moiety of the incoming deoxynucleotide triphosphate (dNTP), we examined how this change in RT-dNTP interaction affects HIV-1 RT fidelity. 2002 The Journal of biological chemistry Abstract HIV Q151N 10 15 RT;RT 214;248 216;250 11932418 Expression of exogenous Sam68, the 68-kilodalton SRC-associated protein in mitosis, is able to alleviate impaired Rev function in astrocytes. Mutagenesis analysis identified the region between amino acids 321 and 410 of Sam68 as being directly involved in the binding of Sam68 to Rev, while a double mutation in Rev, L78D and E79L, like those in the dominant-negative Rev mutant M10, eliminated Rev binding to Sam68. 2002 Journal of virology Abstract HIV E79L;L78D 184;175 188;179 Rev;Rev;Rev;Rev 138;170;226;253 141;173;229;256 11944889 HIV-1 Vif-derived peptide inhibits drug-resistant HIV proteases. In agreement with the in vitro experiments, Vif88-98 has no effect on the production of infectious particles in cells infected with a G48V mutated virus. 2002 Biochemical and biophysical research communications Abstract HIV G48V 134 138 Vif 44 47 11944889 HIV-1 Vif-derived peptide inhibits drug-resistant HIV proteases. Variants of HIV protease bearing the mutation G48V are resistant to inhibition by this Vif-derived peptide, as shown by in vitro assays. 2002 Biochemical and biophysical research communications Abstract HIV G48V 46 50 PR;Vif 16;87 24;90 11948182 Substitutions of Phe61 located in the vicinity of template 5'-overhang influence polymerase fidelity and nucleoside analog sensitivity of HIV-1 reverse transcriptase. F61Y RT had a minimal effect. 2002 The Journal of biological chemistry Abstract HIV F61Y 0 4 RT 5 7 11948182 Substitutions of Phe61 located in the vicinity of template 5'-overhang influence polymerase fidelity and nucleoside analog sensitivity of HIV-1 reverse transcriptase. Mutants displaying the largest increase in fidelity (F61A and F61L) were also the most resistant. 2002 The Journal of biological chemistry Abstract HIV F61A;F61L 53;62 58;66 11948182 Substitutions of Phe61 located in the vicinity of template 5'-overhang influence polymerase fidelity and nucleoside analog sensitivity of HIV-1 reverse transcriptase. The F61A mutant displayed the highest increase in fidelity, followed by the F61L and F61W variants, which had intermediate phenotypes. 2002 The Journal of biological chemistry Abstract HIV F61A;F61L;F61W 4;76;85 8;80;89 11948182 Substitutions of Phe61 located in the vicinity of template 5'-overhang influence polymerase fidelity and nucleoside analog sensitivity of HIV-1 reverse transcriptase. The increase in fidelity of the F61A mutant was corroborated by a 12-fold decrease in its forward mutation rate. 2002 The Journal of biological chemistry Abstract HIV F61A 32 36 11953467 Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. Certain amprenavir-selected mutants conferred greater than 10-fold cross-resistance to lopinavir, including PrL10F/M46I/I50V-GagL449F (19-fold) and PrL10F/M46I/I47V/I50V-GagL449F (31-fold). 2002 AIDS (London, England) Abstract HIV I47V;I50V;I50V;L10F;L10F;M46I;M46I;P10F 160;165;120;150;110;115;155;110 164;169;124;154;114;119;159;114 Gag;Gag;PR;PR 125;170;108;148 128;173;110;150 11953467 Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. Moreover, one isolate with only two mutations in the protease (L10F/84V) and GagL449F displayed a 7.7-fold increase in lopinavir IC50. 2002 AIDS (London, England) Abstract HIV L10F 63 67 PR;Gag 53;77 61;80 11953467 Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. The order of relative replication capacity was wild-type > L10F > L10F/I84V > L10F/M46I/I50V > L10F/M46I/I47V/I50V. 2002 AIDS (London, England) Abstract HIV I47V;I50V;I50V;L10F;L10F;M46I;M46I;I84V;L10F;L10F 105;88;110;78;95;83;100;71;59;66 109;92;114;82;99;87;104;75;63;70 11953467 Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. The replication capacity of viruses containing either I84V or I50V was at least 90% lower than the reference virus in the single-cycle assay. 2002 AIDS (London, England) Abstract HIV I50V;I84V 62;54 66;58 11953470 Drug resistance at low viraemia in HIV-1-infected patients with antiretroviral combination therapy. One patient still had a VL of 300 copies/ml after 28 months, despite the presence of the multidrug-resistance Q151M mutation. 2002 AIDS (London, England) Abstract HIV Q151M 110 115 11955063 Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate. A single amino acid change from methionine 184 to valine in HIV-1 RT (RT(M184V)) has been observed clinically in response to abacavir treatment. 2002 Biochemistry Abstract HIV M184V;M184V 73;32 78;56 RT;RT 66;70 68;72 11955063 Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate. In both DNA- and RNA-directed polymerization, a decrease in the efficiency of CBVTP utilization with respect to dGTP was found with RT(M184V), suggesting that this mutation confers resistance at the level of CBVMP incorporation. 2002 Biochemistry Abstract HIV M184V 135 140 RT 132 134 11955063 Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate. In contrast to CBVTP, D4GTP was found to be an excellent substrate for RT(WT) and no resistance was conferred by the M184V mutation, thus providing novel insight into structure-activity relationships for nucleoside-based inhibitors. 2002 Biochemistry Abstract HIV M184V 117 122 RT 71 73 11955063 Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate. The ability of the natural substrate, dGTP, or CBVTP to be utilized during DNA- and RNA-directed polymerization by RT(WT) and RT(M184V) was defined by pre-steady-state kinetic parameters. 2002 Biochemistry Abstract HIV M184V 129 134 RT;RT 115;126 117;128 11955063 Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate. This compound shows promise as a potent antiviral especially with the drug resistant M184V HIV-1 RT that is so often encountered in a clinical setting. 2002 Biochemistry Abstract HIV M184V 85 90 RT 97 99 11992288 Evolution of human immunodeficiency virus type 1 populations after resumption of therapy following treatment interruption and shift in resistance genotype. Sixty-two percent of patients in whom the V82A and L90M protease mutations were no longer detectable by conventional genotyping still harbored minority resistant variants, in proportions ranging from 0.1% to 21%. 2002 The Journal of infectious diseases Abstract HIV L90M;V82A 51;42 55;46 PR 56 64 12003172 Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals. Among mutations associated with high-level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases, T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one carrying both T215Y and M184V) (1.7%). 2002 Journal of biological regulators and homeostatic agents Abstract HIV K103N;M184V;M184V;T215Y;T215Y;T69D 142;98;222;62;212;116 147;103;227;67;217;120 RT 57 60 12003964 A prospective comparison of the two main indications of efavirenz in 2001 highly active antiretroviral therapy (HAART) regimens: first-line versus salvage use. Viral genotyping detected at least the K103N mutation in 41% of the 78 evaluable patients, despite lack of exposure to efavirenz and related compounds. 2002 The Journal of antimicrobial chemotherapy Abstract HIV K103N 39 44 12005085 Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor. K20R/I) conferred by primary (active site) resistance mutations. 2002 The Pediatric infectious disease journal Abstract HIV K20I;K20R 0;0 6;6 12005085 Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor. L10I) and in vitro nelfinavir cross-resistance. 2002 The Pediatric infectious disease journal Abstract HIV L10I 0 4 12005085 Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor. Ritonavir targeted the well-known pathway containing 82, 54, 46 and other secondary (nonactive site) mutations including T74A. 2002 The Pediatric infectious disease journal Abstract HIV T74A 121 125 12005435 Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes. Since the specificity of this enzyme is not easily determined from the sequences of these cleavage sites alone, we solved the crystal structures of complexes of an inactive variant (D25N) of HIV-1 protease with six peptides that correspond to the natural substrate cleavage sites. 2002 Structure (London, England Abstract HIV D25N 182 186 PR 197 205 12008783 Observations of HIV-1 genotypic drug resistance in a trial of four reverse transcriptase inhibitors (Quattro Trial). During lamivudine monotherapy the M184V mutation was rapidly acquired and viral load rebounded. 2002 Antiviral therapy Abstract HIV M184V 34 39 12008783 Observations of HIV-1 genotypic drug resistance in a trial of four reverse transcriptase inhibitors (Quattro Trial). Resistance to lamivudine (mutation M184V) developed rapidly in all three arms. 2002 Antiviral therapy Abstract HIV M184V 35 40 12008783 Observations of HIV-1 genotypic drug resistance in a trial of four reverse transcriptase inhibitors (Quattro Trial). Zalcitabine monotherapy initially selected M184V mutants, but these were lost as therapy continued. 2002 Antiviral therapy Abstract HIV M184V 43 48 12008787 Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. At week 16, the genotypes in isolates from the abacavir/lamivudine/zidovudine group were M184V alone (n = 3 cases), WT (n = 3) and M184V plus thymidine analogue mutations (TAMs) (n = 1). 2002 Antiviral therapy Abstract HIV M184V;M184V 89;131 94;136 12008787 Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. At week 48, the most common genotype was M184V alone in the abacavir/ lamivudine/zidovudine group (median vRNA 1-2 log,10 below baseline), and M184V with or without TAMs in patients originally assigned to lamivudine/zidovudine. 2002 Antiviral therapy Abstract HIV M184V;M184V 41;143 46;148 12008787 Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. CONCLUSIONS: Abacavir retained efficacy against isolates with the M184V genotype alone. 2002 Antiviral therapy Abstract HIV M184V 66 71 12008787 Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. Despite detectable M184V in 74% of patients on lamivudine/zidovudine, addition of abacavir with or without another antiretroviral therapy resulted in a reduction in vRNA, with 42 of 65 (65%) patients having week 48 vRNA < 400 copies/ml (intent-to-treat with missing = failure). 2002 Antiviral therapy Abstract HIV M184V 19 24 12008787 Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. In the four cases where M184V plus TAMs were detected some mutations were present at baseline. 2002 Antiviral therapy Abstract HIV M184V 24 29 12008787 Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. The genotypes in isolates from the lamivudine/zidovudine group were M184V alone (n = 37), WT ( n= 1) and M184V plus TAMs (n = 3). 2002 Antiviral therapy Abstract HIV M184V;M184V 68;105 73;110 12009869 Human immunodeficiency virus nucleocapsid protein polymorphisms modulate the infectivity of RNA packaging mutants. Conservative amino acid differences between HXB2 and NL4-3 NCs were sufficient to explain the difference in infectivity of viruses carrying the R10A and K11A mutations. 2002 Virology Abstract HIV K11A;R10A 153;144 157;148 NC 59 62 12010361 The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. A number of studies, both of dual nucleoside therapy and HAART, have noted a residual treatment effect for 3TC despite the assumed or observed presence of M184V and high-level phenotypic resistance. 2002 HIV medicine Abstract HIV M184V 155 160 12010361 The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. M184V is both common in the treated population and fitness-reducing. 2002 HIV medicine Abstract HIV M184V 0 5 12010361 The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. The full impact of M184V on therapeutic prospects will require further elucidation; ideally, the risk/benefit of preserving this substitution would be investigated in randomized trials. 2002 HIV medicine Abstract HIV M184V 19 24 12010361 The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. The M184V mutation in the HIV-1 reverse transcriptase gene is primarily associated with rapid, high-level lamivudine (3TC) resistance. 2002 HIV medicine Abstract HIV M184V 4 9 RT 32 53 12010361 The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. The speed and consistency with which this mutation is selected by 3TC under suboptimal viral suppression therefore makes M184V a particularly interesting model for further clinical studies on the association of drug resistance with ongoing treatment benefit. 2002 HIV medicine Abstract HIV M184V 121 126 12010361 The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. While fitness considerations are likely to be a major contributor to the clinical observations noted, there are a number of other potential mechanisms that may contribute to a continuing response to 3TC in the presence of M184V. 2002 HIV medicine Abstract HIV M184V 222 227 12012342 Combining mutations in HIV-1 protease to understand mechanisms of resistance. D30N/V82S mutant showed lower stability than either of the two individual mutations, which is possibly due to concerted changes in the central P2-P2' and S2-S2' sites. 2002 Proteins Abstract HIV V82S;D30N 5;0 9;4 12012342 Combining mutations in HIV-1 protease to understand mechanisms of resistance. Four double mutants, K45I/L90M, K45I/V82S, D30N/V82S, and N88D/L90M were selected for analysis on the basis of observations of increased or decreased stability or enzymatic activity for the respective single mutants. 2002 Proteins Abstract HIV D30N;K45I;K45I;L90M;L90M;N88D;V82S;V82S 43;21;32;63;26;58;37;48 47;25;36;67;30;62;41;52 12012342 Combining mutations in HIV-1 protease to understand mechanisms of resistance. Mutations D30N, K45I, and V82S showed altered interactions with inhibitor residues at P2/P2', P3/P3'/P4/P4', and P1/P1', respectively. 2002 Proteins Abstract HIV D30N;K45I;V82S 10;16;26 14;20;30 12012342 Combining mutations in HIV-1 protease to understand mechanisms of resistance. One of the conformations of Met90 in K45I/L90M has an unfavorably close contact with the carbonyl oxygen of Asp25, as observed previously in the L90M single mutant. 2002 Proteins Abstract HIV K45I;L90M;L90M 37;42;145 41;46;149 Asp 108 111 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Cloned env sequences derived from the plasma virus of subject 30-3 also had single mutations in the GIV sequence (V38M and I37V) detectable following therapy with T-20. 2002 Antimicrobial agents and chemotherapy Abstract HIV I37V;V38M 123;114 127;119 Env 7 10 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Dual mutations involving G36D and other residues within the HR1 domain were also identified. 2002 Antimicrobial agents and chemotherapy Abstract HIV G36D 25 29 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Envs with double mutations (Q32R plus G36D and Q32H plus G36D) exhibited a level of resistance similar to that of G36D alone. 2002 Antimicrobial agents and chemotherapy Abstract HIV G36D;G36D;G36D;Q32H;Q32R 38;57;114;47;28 42;61;118;51;33 Env 0 4 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. In 5 of the 49 env clones, other mutations involving residues 32 (Q32R or Q32H) and 39 (Q39R) were found in combination with G36D. 2002 Antimicrobial agents and chemotherapy Abstract HIV G36D;Q32H;Q32R;Q39R 125;74;66;88 129;78;71;92 Env 15 18 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Sequence analysis of 49 clones derived from the plasma of patient 30-1 on day 14 revealed that 25 clones contained the G36D mutation, while 8 contained the V38A mutation. 2002 Antimicrobial agents and chemotherapy Abstract HIV G36D;V38A 119;156 123;160 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. The I37V mutation resulted in an IC(50) 3.2-fold greater than that of the wild type. 2002 Antimicrobial agents and chemotherapy Abstract HIV I37V 4 8 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. The IC(50) for the V38 M mutation (patient 30-3) was 7.6 microg/ml, an 8-fold increase compared with that of the wild type. 2002 Antimicrobial agents and chemotherapy Abstract HIV V38M 19 24 12019106 Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. The mean 50% inhibition concentrations (IC(50)s) for mutants G36D and V38A (patient 30-1) were 2.3 microg/ml and 11.2 microg/ml, respectively, statistically significant increases of 9.1- and 45-fold, respectively, compared with those of wild-type Env. 2002 Antimicrobial agents and chemotherapy Abstract HIV G36D;V38A 61;70 65;74 Env 247 250 12019110 Longitudinal use of a line probe assay for human immunodeficiency virus type 1 protease predicts phenotypic resistance and clinical progression in patients failing highly active antiretroviral therapy. Combinations of protease mutations (M46I, G48V, I54V, V82A or -F, I84V, and L90M) predicted phenotypic resistance to the protease inhibitor and to nelfinavir. 2002 Antimicrobial agents and chemotherapy Abstract HIV G48V;I54V;I84V;L90M;M46I;V82A 42;48;66;76;36;54 46;52;70;80;40;58 PR;PR 16;121 24;129 12021339 Evolution of replication efficiency following infection with a molecularly cloned feline immunodeficiency virus of low virulence. Further, following subsequent challenge of naive cats with the mutant viruses, the viruses established higher viral loads and induced more marked alterations in CD8(+)-lymphocyte subpopulations than did the parent F14 strain of virus, suggesting that the E409K mutation in the PET(F14) strain contributes to the attenuation of the virus. 2002 Journal of virology Abstract HIV E409K 255 260 12021339 Evolution of replication efficiency following infection with a molecularly cloned feline immunodeficiency virus of low virulence. The variant viruses both carried mutations that reduced the net charge of the V3 loop (K409Q and K409E), giving rise to a reduced ability of the Env proteins to both induce fusion and to establish productive infection in CXCR4-expressing cells. 2002 Journal of virology Abstract HIV K409E;K409Q 97;87 102;93 Env 145 148 12021341 Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. Drug-resistant mutants with a methionine-to-valine substitution at position 184 of reverse transcriptase (M184V) emerged within 5 weeks of initiation of therapy in four newborn macaques infected with simian immunodeficiency virus (SIVmac251) and treated with lamivudine (3TC) or emtricitabine [(-)-FTC] (two animals per drug). 2002 Journal of virology Abstract HIV M184V;M184V 106;30 111;79 RT 83 104 12021341 Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. These data demonstrate that the M184V mutation in SIV conferred a slightly reduced fitness but did not affect disease outcome. 2002 Journal of virology Abstract HIV M184V 32 37 12021341 Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. Thus, this animal model mimics the rapid emergence of M184V mutants of HIV-1 during 3TC therapy of human patients. 2002 Journal of virology Abstract HIV M184V 54 59 12021341 Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. To further evaluate the effect of the M184V mutation on viral fitness and virulence, groups of juvenile macaques were inoculated with the molecular clone SIVmac239 with either the wild-type sequence (group A [n = 5]) or the M184V sequence (SIVmac239-184V; group B [n = 5] and group C [n = 2]). 2002 Journal of virology Abstract HIV M184V;M184V 38;224 43;229 12036490 HIV-1 subtype C reverse transcriptase sequences from drug-naive pregnant women in South Africa. An additional three patients harbored V118I, which can function as an accessory resistance mutation, but in this context is also likely to be a polymorphism. 2002 AIDS research and human retroviruses Abstract HIV V118I 38 43 12036490 HIV-1 subtype C reverse transcriptase sequences from drug-naive pregnant women in South Africa. Polymorphisms at these loci occurred infrequently, with three patients harboring the A98S and V179I polymorphisms. 2002 AIDS research and human retroviruses Abstract HIV A98S;V179I 85;94 89;99 12045487 Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. Compared to placebo, significant reductions in HIV-1 RNA were observed for tenofovir DF-treated patients who had thymidine analog- (TAM), lamivudine- (M184V), NNRTI- or protease inhibitor-associated mutations. 2002 AIDS (London, England) Abstract HIV M184V 151 156 PR;NNRTI 169;159 177;164 12045487 Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. Four patients (2%) developed the K65R mutation (selected by tenofovir in vitro) and showed 3- to 4-fold reductions in tenofovir susceptibility but no evidence of rebound viremia. 2002 AIDS (London, England) Abstract HIV K65R 33 37 12050397 A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. A systematic search of a large phenotypic-genotypic database (Virco) linked the Y318F substitution with a >10-fold decrease in NNRTI susceptibility in >85% of clinically derived isolates. 2002 Journal of virology Abstract HIV Y318F 80 85 NNRTI 127 132 12050397 A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. Combinations of Y318F with K103N, Y181C, or both resulted in decreased efavirenz susceptibility of 43-, 3.3-, and 84-fold, respectively, as well as >100- and >60-fold decreases in delavirdine and nevirapine susceptibility, respectively. 2002 Journal of virology Abstract HIV K103N;Y181C;Y318F 27;34;16 32;39;21 12050397 A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. The Y318F substitution in the 3' region of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has been linked to nonnucleoside RT inhibitor (NNRTI) resistance in vitro. 2002 Journal of virology Abstract HIV Y318F 4 9 RT;NNRTI;RT;RT 87;161;110;147 108;166;112;149 12050397 A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. There was a significant association between Y318F and use of delavirdine (P = 10(-11)) and nevirapine (P = 10(-6)) but not efavirenz (P = 0.3). 2002 Journal of virology Abstract HIV Y318F 44 49 12050397 A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. These results indicate the importance of the Y318F substitution in HIV-1 drug resistance. 2002 Journal of virology Abstract HIV Y318F 45 50 12051725 Effects of remote mutation on the autolysis of HIV-1 PR: X-ray and NMR investigations. Autolysis rates of the C95M and C95M/C1095A mutants of a HIV-1 protease tethered dimer have been determined by real time NMR and it is observed that the double mutant has approximately two times higher rate. 2002 Biochemical and biophysical research communications Abstract HIV C1095A;C95M;C95M 37;23;32 43;27;36 PR 63 71 12051725 Effects of remote mutation on the autolysis of HIV-1 PR: X-ray and NMR investigations. Comparison of the double mutant structure with that of C95M single mutant reveals that there is a shift in the position of the catalytic aspartates and the bound catalytic water. 2002 Biochemical and biophysical research communications Abstract HIV C95M 55 59 12051725 Effects of remote mutation on the autolysis of HIV-1 PR: X-ray and NMR investigations. X-ray structure of the C95M/C1095A double mutant has been solved and refined to 2.1 A resolution. 2002 Biochemical and biophysical research communications Abstract HIV C1095A;C95M 28;23 34;27 12060879 Discordant Human Immunodeficiency Virus Type 1 drug resistance mutations, including K103N, observed in cerebrospinal fluid and plasma. To our knowledge, this is the first report of HIV-1 isolated from CSF harboring the K103N mutation, which confers resistance to the nonnucleoside reverse-transcriptase inhibitors, and this finding may indicate that virus in the CSF replicates independently from virus in the blood compartment. 2002 Clinical infectious diseases Abstract HIV K103N 84 89 NNRTI 132 167 12069959 Genetic divergence of human immunodeficiency virus type 1 Ethiopian clade C reverse transcriptase (RT) and rapid development of resistance against nonnucleoside inhibitors of RT. After selection with DLV, a polymorphism, A62A, initially observed in the Ethiopian isolate 4762, mutated to A62V; the latter is a secondary substitution associated with multidrug resistance against nucleoside RT inhibitors. 2002 Antimicrobial agents and chemotherapy Abstract HIV A62A;A62V 42;109 46;113 RT 210 212 12069959 Genetic divergence of human immunodeficiency virus type 1 Ethiopian clade C reverse transcriptase (RT) and rapid development of resistance against nonnucleoside inhibitors of RT. Genotypic analysis showed that two Ethiopian isolates naturally harbored the mutations K70R and G190A associated with resistance to ZDV and nonnucleoside reverse transcriptase inhibitors, respectively. 2002 Antimicrobial agents and chemotherapy Abstract HIV G190A;K70R 96;87 101;91 NNRTI 140 175 12069959 Genetic divergence of human immunodeficiency virus type 1 Ethiopian clade C reverse transcriptase (RT) and rapid development of resistance against nonnucleoside inhibitors of RT. In the case of subtype C, selection with NVP and/or EFV led to the appearance of several previously unseen mutations in RT, i.e., V106M and S98I, as well as other mutations that have been previously reported (e.g., K103N, V106A, V108I, and Y181C). 2002 Antimicrobial agents and chemotherapy Abstract HIV K103N;S98I;V106A;V106M;V108I;Y181C 215;140;222;130;229;240 220;144;227;135;234;245 RT 120 122 12069959 Genetic divergence of human immunodeficiency virus type 1 Ethiopian clade C reverse transcriptase (RT) and rapid development of resistance against nonnucleoside inhibitors of RT. Phenotypic assays revealed that the K70R substitution in this context did not reduce susceptibility to ZDV, whereas the G190A substitution resulted in high-level resistance to nevirapine (NVP). 2002 Antimicrobial agents and chemotherapy Abstract HIV G190A;K70R 120;36 125;40 12069972 ATP-dependent removal of nucleoside reverse transcriptase inhibitors by human immunodeficiency virus type 1 reverse transcriptase. Recombinant wild-type and mutant HIV type 1 (HIV-1) RT enzymes with thymidine analog resistance mutations D67N, K70R, and T215Y were analyzed for their ability to remove eight nucleoside reverse transcriptase inhibitors in the presence of physiological concentrations of ATP. 2002 Antimicrobial agents and chemotherapy Abstract HIV D67N;K70R;T215Y 106;112;122 110;116;127 NRTI;RT 176;52 208;54 12069983 Pressure of zidovudine accelerates the reversion of lamivudine resistance-conferring M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1. We cultured lamivudine-resistant human immunodeficiency virus type 1 (HIV-1) variants over an extended period of time in the presence of zidovudine and observed a premature reversion of the resistance-conferring M184V mutation. 2002 Antimicrobial agents and chemotherapy Abstract HIV M184V 212 217 12072945 Prevalence of genotypic resistance in untreated HIV patients in Spain. Primary mutations in the protease gene were detected in 12% of cases; V82A was the mutation most frequently detected (11/12, 91.6%). 2002 European journal of clinical microbiology & infectious diseases Abstract HIV V82A 70 74 PR 25 33 12072945 Prevalence of genotypic resistance in untreated HIV patients in Spain. Primary mutations in the reverse transcriptase gene were found in two (2.2%) samples: M41L, K70R and M184 V were found in one sample and K70R in another. 2002 European journal of clinical microbiology & infectious diseases Abstract HIV K70R;K70R;M184V;M41L 92;137;101;86 96;141;107;90 RT 25 46 12074693 Application of a colorimetric chain-termination assay for characterization of reverse transcriptase from 3'-azido-2',3'-deoxythymidine-resistant HIV isolates. The four deviating isolates contained either a minimum of four AZT-specific substitutions, including Thr-215-->Tyr (isolates 134 and 143), or some of the known specific substitutions combined with Thr-39-->Ala (isolates 80 and 157). 2002 Biotechnology and applied biochemistry Abstract HIV T215T;T39A 101;197 114;209 12074693 Application of a colorimetric chain-termination assay for characterization of reverse transcriptase from 3'-azido-2',3'-deoxythymidine-resistant HIV isolates. The Thr-39-->Ala substitution has previously been recorded in connection with AZT/Foscarnet combination therapy. 2002 Biotechnology and applied biochemistry Abstract HIV T39A 4 16 12079565 Genetic variation of the protease and reverse transcriptase genes in HIV-1 CRF04_cpx strains. Substitutions classically associated with resistance to antiretroviral drugs were observed in six of seven samples, including G48V, V82A, L90M, M46I in the protease protein, and K70R, D69D/N, M184V, T215F, K103N in the reverse transcriptase protein. 2002 AIDS research and human retroviruses Abstract HIV D69D;D69N;G48V;K103N;K70R;L90M;M184V;M46I;T215F;V82A 184;184;126;206;178;138;192;144;199;132 190;190;130;211;182;142;197;148;204;136 RT;PR 219;156 240;164 12083326 Human immunodeficiency virus 1 strains resistant to nucleoside inhibitors of reverse transcriptase in isolates from the Czech Republic as monitored by line probe assay and nucleotide sequencing. Mutations in RT gene (M41L, K70R and T215Y/F) conferring the resistance to zidovudine (ZDV) were most frequent (62.6%), that (M184V) responsible for the resistance to lamivudine (3TC) was less frequent (33.7%), while those linked to the resistance to dideoxyinosine (ddl) and dideoxyinosine together with dideoxycytidine (ddl/ddC) were rather rare (6.5% and 5.1%, respectively). 2001 Acta virologica Abstract HIV K70R;M184V;M41L;T215F;T215Y 28;126;22;37;37 32;131;26;44;44 RT 13 15 12088824 Inclusion of full length human immunodeficiency virus type 1 (HIV-1) gag sequences in viral recombinants applied to drug susceptibility phenotyping. Mutations known to cause retarded viral growth kinetics (RT M184V and PR I50V) were introduced and analyzed in parallel using both the new Five Prime HIV assay (FPH) and a standard recombinant virus assay (RVA). 2002 Journal of virological methods Abstract HIV I50V;M184V 73;60 77;65 PR;RT 70;57 72;59 12088824 Inclusion of full length human immunodeficiency virus type 1 (HIV-1) gag sequences in viral recombinants applied to drug susceptibility phenotyping. The M184V and I50V mutants produced up to 4.8- and 5.9-fold higher p24 antigen levels, respectively, with the FPH when compared to the cultures containing RVA-derived viruses. 2002 Journal of virological methods Abstract HIV I50V;M184V 14;4 18;9 p24 67 70 12093278 Amplification of the effects of drug resistance mutations by background polymorphisms in HIV-1 protease from African subtypes. In this paper we present a complete thermodynamic dissection of the differences between proteases from different subtypes and the effects of the V82F/I84V drug-resistant mutation within the framework of the B, C, and A subtypes. 2002 Biochemistry Abstract HIV I84V;V82F 150;145 154;149 PR 88 97 12093278 Amplification of the effects of drug resistance mutations by background polymorphisms in HIV-1 protease from African subtypes. Relative to the wild-type B subtype protease, the V82F/I84V drug-resistant mutation within the C and A subtypes lowers the binding affinity of inhibitors by factors ranging between 40 and 3000. 2002 Biochemistry Abstract HIV I84V;V82F 55;50 59;54 PR 36 44 12093916 Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Insertion of patient-derived Vpr alleles or a Q3R substitution into a cytopathic HIV-1 clone resulted in a marked impairment of cytopathicity without affecting viral replication efficiency. 2002 Proc Natl Acad Sci U S A Abstract HIV Q3R 46 49 Vpr 29 32 12093916 Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Vpr alleles derived from this patient contained both premature stop codons and an unusual Q3R polymorphism. 2002 Proc Natl Acad Sci U S A Abstract HIV Q3R 90 93 Vpr 0 3 12097136 The role of phenylalanine-119 of the reverse transcriptase of mouse mammary tumour virus in DNA synthesis, ribose selection and drug resistance. Owing to the uniqueness of MMTV as a type B retrovirus, we have generated a Phe-119-Val mutant of MMTV RT to study the involvement of this residue in affecting the catalytic features of this RT. 2002 The Biochemical journal Abstract HIV F119V 76 87 RT;RT 103;191 105;193 12097136 The role of phenylalanine-119 of the reverse transcriptase of mouse mammary tumour virus in DNA synthesis, ribose selection and drug resistance. The Phe-119-Val mutant is also different from the wild-type enzyme in its preference for most template primers tested and in its ability to synthesize DNA under non-processive and processive conditions. 2002 The Biochemical journal Abstract HIV F119V 4 15 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. In both single- and multiple-cycle assay systems and in the context of I50V, the L449F and P453L changes consistently increased the 50% inhibitory concentration of APV, while the CS changes alone had no measurable effect on inhibitor sensitivity. 2002 Journal of virology Abstract HIV I50V;L449F;P453L 71;81;91 75;86;96 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. In population-based sequence analyses the I50V mutant was invariably linked to either L449F or P453L. 2002 Journal of virology Abstract HIV I50V;L449F;P453L 42;86;95 46;91;100 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. Purified I50V protease catalyzed cleavage of decapeptides incorporating the L449F or P453L change 10-fold and 22-fold more efficiently than cleavage of the wild-type substrate, respectively. 2002 Journal of virology Abstract HIV I50V;L449F;P453L 9;76;85 13;81;90 PR 14 22 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. Querying a central resistance data repository resulted in the detection of significant associations (P < 0.001) between the presence of APV protease signature mutations and Gag L449F (p1/p6 LP1'F) and P453L (p1/p6 PP5'L) CS changes. 2002 Journal of virology Abstract HIV L449F;P453L 177;201 182;206 PR;Gag;Gag;Gag 140;173;187;211 148;176;189;213 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. Sequential plasma samples from one patient revealed a transition from I50V M46L P453L viruses at early time points to I50V M46I L449F viruses in later samples. 2002 Journal of virology Abstract HIV I50V;I50V;L449F;M46I;M46L;P453L 70;118;128;123;75;80 74;122;133;127;79;85 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. The decreased in vitro fitness of the I50V mutant was only partially improved by addition of either CS change (I50V M46I L449F mutant replicative capacity approximately 16% of that of wild-type virus). 2002 Journal of virology Abstract HIV I50V;I50V;L449F;M46I 38;111;121;116 42;116;126;120 12097552 Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. Western blot analysis of Pr55 Gag precursor cleavage products from infected-cell cultures indicated accumulation of uncleaved Gag p1-p6 in all I50V viruses without coexisting CS changes. 2002 Journal of virology Abstract HIV I50V 143 147 Gag;Gag;Gag;PR 30;126;133;25 33;129;135;27 12097566 Different effects of Nef-mediated HLA class I down-regulation on human immunodeficiency virus type 1-specific CD8(+) T-cell cytolytic activity and cytokine production. HIV-1-specific CTL clones were not able to kill primary CD4(+) T cells infected with a Nef-positive HIV-1 strain (NL-432) but efficiently lysed CD4(+) T cells infected with NL-M20A. 2002 Journal of virology Abstract HIV M20A 176 180 Nef 87 90 12097566 Different effects of Nef-mediated HLA class I down-regulation on human immunodeficiency virus type 1-specific CD8(+) T-cell cytolytic activity and cytokine production. Interestingly, CTL clones stimulated with NL-432-infected CD4(+) T cells were able to produce cytokines, albeit at a lower level than when stimulated with NL-M20A-infected CD4(+) T cells. 2002 Journal of virology Abstract HIV M20A 158 162 12097566 Different effects of Nef-mediated HLA class I down-regulation on human immunodeficiency virus type 1-specific CD8(+) T-cell cytolytic activity and cytokine production. Replication of NL-432 was partially suppressed in a coculture of HIV-1-infected CD4(+) T cells and HIV-1-specific CTL clones, while replication of NL-M20A was completely suppressed. 2002 Journal of virology Abstract HIV M20A 150 154 HIV infections 65 79 12097566 Different effects of Nef-mediated HLA class I down-regulation on human immunodeficiency virus type 1-specific CD8(+) T-cell cytolytic activity and cytokine production. We confirmed this effect by using a nef-mutant HIV-1 strain (NL-M20A) that expresses a Nef protein which does not induce down-regulation of HLA class I molecules but is otherwise functional. 2002 Journal of virology Abstract HIV M20A 64 68 Nef;Nef 36;87 39;90 12097569 Mutation of the catalytic domain of the foamy virus reverse transcriptase leads to loss of processivity and infectivity. Despite the presence of approximately 50% of wild-type RT activity in RT-V313M virions, full-length DNA products were not detected in transfected cells. 2002 Journal of virology Abstract HIV V313M 73 78 RT;RT 55;70 57;72 12097569 Mutation of the catalytic domain of the foamy virus reverse transcriptase leads to loss of processivity and infectivity. However, the V313M mutant has about 40% of the wild-type level of FV RT activity and has a lower processivity than the wild-type FV enzyme. 2002 Journal of virology Abstract HIV V313M 13 18 RT 69 71 12097569 Mutation of the catalytic domain of the foamy virus reverse transcriptase leads to loss of processivity and infectivity. The V313M mutant RT is also relatively resistant to 3TC. 2002 Journal of virology Abstract HIV V313M 4 9 RT 17 19 12097569 Mutation of the catalytic domain of the foamy virus reverse transcriptase leads to loss of processivity and infectivity. These results suggest that the decrease in RT activity and processivity of FV RT-V313M prevents completion of reverse transcription and greatly diminishes viral replication. 2002 Journal of virology Abstract HIV V313M 81 86 RT;RT;RT 110;43;78 131;45;80 12097569 Mutation of the catalytic domain of the foamy virus reverse transcriptase leads to loss of processivity and infectivity. Unexpectedly, the resultant virus, SFVcpz(hu) RT-V313M, replicated poorly, and Met rapidly reverted to Val. 2002 Journal of virology Abstract HIV V313M 49 54 RT 46 48 12097605 Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. Aspartate 368 on human immunodeficiency virus type 1 (HIV-1) gp120 forms multiple contacts with CD4; in mutagenesis studies, its replacement by asparagine and corresponding changes in simian immunodeficiency virus SIVmac (D385N) reduced binding with CD4. 2002 Journal of virology Abstract HIV D385N 222 227 gp120 61 66 12097605 Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. Extending these observations, we also found D385N to be dominant among env clones from two rhesus macaques that progressed rapidly to simian AIDS. 2002 Journal of virology Abstract HIV D385N 44 49 Env 71 74 AIDS 141 145 12097605 Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. However, the gp120s with D385N and G383R showed a 40-fold reduction in affinity, with a drastic increase in dissociation rate, indicating an inherently unstable complex. 2002 Journal of virology Abstract HIV D385N;G383R 25;35 30;40 gp120 13 19 12097605 Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. Moreover, an adjacent change, G383R, which was frequently coselected with D385N, further decreased binding. 2002 Journal of virology Abstract HIV D385N;G383R 74;30 79;35 12097605 Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. Nevertheless, simian immunodeficiency virus envelopes with D385N were prevalent in several studies. 2002 Journal of virology Abstract HIV D385N 59 64 Env 44 53 12118466 Prevalence of HIV-1 polymerase gene mutations in pre-treated patients in Thailand. The mutations associated with lamivudine resistance (M184V/I) were found most often (in 45.7% of individuals). 2002 The Southeast Asian journal of tropical medicine and public health Abstract HIV M184I;M184V 53;53 60;60 12118466 Prevalence of HIV-1 polymerase gene mutations in pre-treated patients in Thailand. The stavudine-resistant mutant (V75T) and T69 insertions were not found. 2002 The Southeast Asian journal of tropical medicine and public health Abstract HIV V75T 32 36 12118466 Prevalence of HIV-1 polymerase gene mutations in pre-treated patients in Thailand. Zidovudine-resistant mutants: T215Y/F (36%), M41L (28%) and K70R (25.3%) were common; but mutations linked to didanosine (L74V) and multinucleoside-resistant genotypes (Q151M) were rarely recognized (2.4% and 3.6%, respectively). 2002 The Southeast Asian journal of tropical medicine and public health Abstract HIV K70R;L74V;M41L;Q151M;T215F;T215Y 60;122;45;169;30;30 64;126;49;174;37;37 12119300 Increased affinity and stability of an anti-HIV-1 envelope immunotoxin by structure-based mutagenesis. Detailed analysis of one such mutant, N31H/Q100eY, revealed both a higher affinity for monomeric and cell surface Env and an increased stability against aggregation compared with the starting immunotoxin. 2002 The Journal of biological chemistry Abstract HIV N31H 38 42 Env 114 117 12119300 Increased affinity and stability of an anti-HIV-1 envelope immunotoxin by structure-based mutagenesis. N31H/Q100eY retained the ability to bind to Env from multiple viral isolates, to inhibit Env-mediated cell fusion, and to limit spreading viral infection in peripheral blood mononuclear cells. 2002 The Journal of biological chemistry Abstract HIV N31H 0 4 Env;Env 44;89 47;92 12126720 Prevalence of mutations related to HIV-1 antiretroviral resistance in Brazilian patients failing HAART. In the pro gene the main mutation found was L90M (26%) followed by dual substitution in L90M and V82A (6%). 2002 Journal of clinical virology Abstract HIV L90M;L90M;V82A 44;88;97 48;92;101 12126720 Prevalence of mutations related to HIV-1 antiretroviral resistance in Brazilian patients failing HAART. The main mutation found in RT gene was the M184V (48%) followed by T69D/N (47%), T215Y/F (46%), M41L (39%), and L74V (7%). 2002 Journal of clinical virology Abstract HIV L74V;M184V;M41L;T215F;T215Y;T69D;T69N 112;43;96;81;81;67;67 116;48;100;88;88;73;73 RT 27 29 12131189 Evolving patterns of HIV-1 resistance to antiretroviral agents in newly infected individuals. Hypersusceptibility to PI decreased from 18.3% to 5.4% (P = 0.02) while the amino acid substitutions in PR increased over time: M36I (6.6% to 19.7%) and A71V/T (3.9% to 15.8%). 2002 AIDS (London, England) Abstract HIV A71T;A71V;M36I 153;153;128 159;159;132 PI;PR 23;104 25;106 12131194 Kinetics of CD4 cells after discontinuation of antiretroviral therapy in patients with virological failure and a CD4 cell count greater than 500 cells/microl. This decline was unrelated to the CD4 cell count and HIV-RNA values at interruption, but was more profound in patients in whom the M184V mutation had disappeared after lamivudine discontinuation. 2002 AIDS (London, England) Abstract HIV M184V 131 136 12131209 Virologic response to nelfinavir-based regimens: pharmacokinetics and drug resistance mutations (VIRAPHAR study). According to multivariate analysis, NFV Cmin and Cmax, CD4 cell count, number of baseline RT + protease gene mutations, D67N, M184V, T215F/Y in RT, and M36I in protease, were independent factors that were significantly predictive of failure. 2002 AIDS (London, England) Abstract HIV D67N;M184V;M36I;T215F;T215Y 120;126;152;133;133 124;131;156;140;140 PR;PR;RT;RT 95;160;90;144 103;168;92;146 12131209 Virologic response to nelfinavir-based regimens: pharmacokinetics and drug resistance mutations (VIRAPHAR study). At failure, L10I, D30N, M36I, V77I, N88S/D or L90M protease mutations had emerged since baseline. 2002 AIDS (London, England) Abstract HIV D30N;L10I;L90M;M36I;N88D;N88S;V77I 18;12;46;24;36;36;30 22;16;50;28;42;42;34 PR 51 59 12131564 Virologic rebound on HAART in the context of low treatment adherence is associated with a low prevalence of antiretroviral drug resistance. In the viremic group, substitutions in HIV protease were detected most frequently in the following positions in subjects on indinavir (IDV): L10I/V (35.7%), M46I/L (35.7%), A71T/V (35.7%), V82A (42.9%); and for subjects on nelfinavir (NFV): D30N (50.0%), V77I (56.3%), N88D (37.5%). 2002 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A71T;A71V;D30N;L10I;L10V;M46I;M46L;N88D;V77I;V82A 173;173;241;141;141;157;157;269;255;189 179;179;245;147;147;163;163;273;259;193 PR 43 51 12134253 Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. The most common mutation was K103N, which was present in 10 women. 2002 The Journal of infectious diseases Abstract HIV K103N 29 34 12142445 Overcoming drug resistance in HIV-1 chemotherapy: the binding thermodynamics of Amprenavir and TMC-126 to wild-type and drug-resistant mutants of the HIV-1 protease. Biochemical and clinical studies have shown that, unlike other inhibitors, Amprenavir is severely affected by the protease mutation I50V, located in the flap region of the enzyme. 2002 Protein science Abstract HIV I50V 132 136 PR 114 122 12142445 Overcoming drug resistance in HIV-1 chemotherapy: the binding thermodynamics of Amprenavir and TMC-126 to wild-type and drug-resistant mutants of the HIV-1 protease. In this paper, we have studied the thermodynamic and molecular origin of the response of these two inhibitors to the I50V mutation and the double active-site mutation V82F/I84V that affects all existing clinical inhibitors. 2002 Protein science Abstract HIV I50V;I84V;V82F 117;172;167 121;176;171 12142445 Overcoming drug resistance in HIV-1 chemotherapy: the binding thermodynamics of Amprenavir and TMC-126 to wild-type and drug-resistant mutants of the HIV-1 protease. The mutations I50V and V82F/I84V lower the binding affinity of Amprenavir by a factor of 147 and 104, respectively. 2002 Protein science Abstract HIV I50V;I84V;V82F 14;28;23 18;32;27 12142445 Overcoming drug resistance in HIV-1 chemotherapy: the binding thermodynamics of Amprenavir and TMC-126 to wild-type and drug-resistant mutants of the HIV-1 protease. The mutations I50V and V82F/I84V lower the binding affinity of TMC-126 by only a factor of 16 and 11, respectively, indicating that the binding affinity of TMC-126 to the drug-resistant mutants is still higher than the affinity of Amprenavir to the wild-type protease. 2002 Protein science Abstract HIV I50V;I84V;V82F 14;28;23 18;32;27 PR 259 267 12142445 Overcoming drug resistance in HIV-1 chemotherapy: the binding thermodynamics of Amprenavir and TMC-126 to wild-type and drug-resistant mutants of the HIV-1 protease. TMC-126 is a second-generation inhibitor, chemically related to Amprenavir, with a reported extremely low susceptibility to existing resistant mutations including I50V. 2002 Protein science Abstract HIV I50V 163 167 12163585 Nelfinavir-resistant, amprenavir-hypersusceptible strains of human immunodeficiency virus type 1 carrying an N88S mutation in protease have reduced infectivity, reduced replication capacity, and reduced fitness and process the Gag polyprotein precursor aberrantly. Addition of mutation M46L to a strain harboring mutations L63P, V77I, and N88S resulted in a reduction of fitness and infectivity without changing Gag-processing efficiency, while amprenavir hypersusceptibility was further diminished. 2002 Journal of virology Abstract HIV L63P;M46L;N88S;V77I 58;21;74;64 62;25;78;68 Gag 147 150 12163585 Nelfinavir-resistant, amprenavir-hypersusceptible strains of human immunodeficiency virus type 1 carrying an N88S mutation in protease have reduced infectivity, reduced replication capacity, and reduced fitness and process the Gag polyprotein precursor aberrantly. Here we demonstrate that substitutions L63P and V77I in protease, in combination, partially compensate for the loss of fitness, loss of replication capacity, loss of specific infectivity, and aberrant Gag processing induced by the N88S mutation. 2002 Journal of virology Abstract HIV L63P;N88S;V77I 39;231;48 43;235;52 PR;Gag 56;201 64;204 12163585 Nelfinavir-resistant, amprenavir-hypersusceptible strains of human immunodeficiency virus type 1 carrying an N88S mutation in protease have reduced infectivity, reduced replication capacity, and reduced fitness and process the Gag polyprotein precursor aberrantly. The N88S mutation occurring in some of these subjects induces amprenavir hypersusceptibility and a reduction of fitness and replication capacity. 2002 Journal of virology Abstract HIV N88S 4 8 12163585 Nelfinavir-resistant, amprenavir-hypersusceptible strains of human immunodeficiency virus type 1 carrying an N88S mutation in protease have reduced infectivity, reduced replication capacity, and reduced fitness and process the Gag polyprotein precursor aberrantly. The ratio of reverse transcriptase activity to p24 protein was reduced in this strain compared to that in the other variants, suggesting that the M46L effect on fitness occurred through a mechanism different from a Gag-processing defect. 2002 Journal of virology Abstract HIV M46L 146 150 RT;p24;Gag 13;47;215 34;50;218 12163607 Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. A variant SOS gp140, designated SOSIP gp140, contains an isoleucine-to-proline substitution at position 559 in the N-terminal heptad repeat region of gp41. 2002 Journal of virology Abstract HIV I559P 57 107 gp140;gp140;gp41 14;38;150 19;43;154 12163615 The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus. Our results indicate that M184V impaired viral fitness in pair-wise comparisons of mutants that contained or lacked this substitution. 2002 Journal of virology Abstract HIV M184V 26 31 12163615 The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus. Since the M184V mutation in human immunodeficiency virus type 1 reverse transcriptase is associated with diminished fitness as well as lamivudine resistance, we introduced this substitution into several of our deletion mutants to determine its effects on viral replication and compensatory reversion. 2002 Journal of virology Abstract HIV M184V 10 15 RT 64 85 12163615 The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus. We also observed that M184V significantly impaired the potential for both compensatory mutagenesis and reversion in these mutants both in cell lines and in peripheral blood mononuclear cells. 2002 Journal of virology Abstract HIV M184V 22 27 12167268 Extent and importance of cross-resistance to efavirenz after nevirapine failure. 聽Virological failure was observed in patients with phenotypic resistance to efavirenz (67 vs. 11%; relative risk [RR], 4; 95% confidence interval [CI], 1.07-14.89; p = 0.04), or in presence of the K103N mutation (52 vs. 17%; RR, 1.77; 95% CI, 1.12-2.79; p = 0.02), and these results remained unchanged after adjusting for HIV load, or by resistance to the accompanying drugs in the salvage regimen. 2002 AIDS research and human retroviruses Abstract HIV K103N 197 202 12167268 Extent and importance of cross-resistance to efavirenz after nevirapine failure. All the strains with the K103N mutation showed high-level resistance to efavirenz, in contrast with 20% of those carrying exclusively the Y181C mutation. 2002 AIDS research and human retroviruses Abstract HIV K103N;Y181C 25;138 30;143 12169210 Comparative study of some energetic and steric parameters of the wild type and mutants HIV-1 protease: a way to explain the viral resistance. Because, in vivo, the HIV-1 PR ( HIV-1 protease) present a high mutation rate we performed a comparative study of the energetic behaviors of the wild type HIV-1 PR and four type of mutants: Val82/Asn; Val82/Asp; Gln7/Lys, Leu33/Ile, Leu63/Ile; Ala71/Thr, Val82/Ala. 2002 Journal of cellular and molecular medicine Abstract HIV A71T;L33I;L63I;Q7K;V82A;V82D;V82N 244;222;233;212;255;201;190 253;231;242;220;264;210;199 PR;Asp;PR;PR 39;207;28;161 47;210;30;163 12172093 M184V is associated with a low incidence of thymidine analogue mutations and low phenotypic resistance to zidovudine and stavudine. The number of thymidine analogue mutations (TAMs) was lower in isolates with M184V, this was independent of plasma HIV-1-RNA level and time on therapy for T215F/Y, D67N and L210W. 2002 AIDS (London, England) Abstract HIV D67N;L210W;M184V;T215F;T215Y 164;173;77;155;155 168;178;82;162;162 12172093 M184V is associated with a low incidence of thymidine analogue mutations and low phenotypic resistance to zidovudine and stavudine. The resistance of HIV clinical isolates with or without M184V was analysed in relation to plasma HIV-1-RNA level and time on therapy. 2002 AIDS (London, England) Abstract HIV M184V 56 61 12172093 M184V is associated with a low incidence of thymidine analogue mutations and low phenotypic resistance to zidovudine and stavudine. This suggests a direct effect of M184V on the reduced selection of TAMs. 2002 AIDS (London, England) Abstract HIV M184V 33 38 12176989 Mechanistic studies to understand the progressive development of resistance in human immunodeficiency virus type 1 reverse transcriptase to abacavir. It was found that, similar to the multidrug-resistant mutant reverse transcriptase (RT)(Q151M), the mutations L74V, M184V, and a triple mutant containing L74V/Y115F/M184V all caused increased selectivity for dGTP over the active metabolite of abacavir (carbovir triphosphate). 2002 The Journal of biological chemistry Abstract HIV L74V;M184V;Y115F;L74V;M184V;Q151M 154;165;159;110;116;88 158;170;164;114;121;93 RT;RT 61;84 82;86 12176989 Mechanistic studies to understand the progressive development of resistance in human immunodeficiency virus type 1 reverse transcriptase to abacavir. The triple mutant showed no advantage in selectivity over RT(M184V) and was severely impaired in its ability to remove a chain terminator, giving no kinetic basis for its increased resistance in a cellular system. 2002 The Journal of biological chemistry Abstract HIV M184V 61 66 RT 58 60 12180647 Resistance profiles of cyclic and linear inhibitors of HIV-1 protease. Kinetic analysis of the mutants revealed that catalytic efficiency was 1-30% of that for the wild-type enzyme, a consequence of reduced kcat in all cases and an increased KM for all mutants except for the G48V enzyme. 2002 Antiviral chemistry & chemotherapy Abstract HIV G48V 205 209 12180647 Resistance profiles of cyclic and linear inhibitors of HIV-1 protease. The greatest increase in Ki was generally observed for the 184V mutant and least for the G48V/L90M mutant, and additional combinations of mutations did not result in improved inhibition profiles for the cyclic compounds. 2002 Antiviral chemistry & chemotherapy Abstract HIV G48V;L90M 89;94 93;98 12180647 Resistance profiles of cyclic and linear inhibitors of HIV-1 protease. The overall structure-inhibitory profiles of the cyclic compounds were similar, and the inhibition of the V82A, 184V and G48V/L90M mutants were less efficient than of the wild-type enzyme. 2002 Antiviral chemistry & chemotherapy Abstract HIV G48V;L90M;V82A 121;126;106 125;130;110 12180647 Resistance profiles of cyclic and linear inhibitors of HIV-1 protease. To allow a detailed structure-inhibition analysis, enzyme with single, double, triple and quadruple combinations of G48V, V82A, 184V and L90M substitutions was used. 2002 Antiviral chemistry & chemotherapy Abstract HIV G48V;L90M;V82A 116;137;122 120;141;126 12183249 Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients. Additional PI resistance mutations, including primary mutation I50V, could be selected in patients failing on LPV/r. 2002 Antimicrobial agents and chemotherapy Abstract HIV I50V 63 67 PI 11 13 12183249 Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients. An LPV mutation score of >5 mutations, the presence of the PR I54V mutation at baseline, a high number of previous PIs, prior therapy with ritonavir or indinavir, absence of coprescription of efavirenz, and a lower exposure to LPV or lower LPV trough concentrations were independently associated with VF on LPV/r. 2002 Antimicrobial agents and chemotherapy Abstract HIV I54V 62 66 PI;PR 115;59 118;61 12186898 Nucleoside analog resistance caused by insertions in the fingers of human immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated excision. Although the dideoxynucleoside analogs of other nucleosides were excised more slowly than AZTMP, ddTMP, and d4TMP, the mutants with the fingers insertion and T215Y excised all of the nucleoside analogs that were tested more efficiently than wild-type RT or a mutant RT carrying the classical AZT resistance mutations. 2002 Journal of virology Abstract HIV T215Y 158 163 RT;RT 251;266 253;268 12186898 Nucleoside analog resistance caused by insertions in the fingers of human immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated excision. However, unlike the classic AZT resistance mutations (M41L/D67N/K70R/T215Y or F/K219E or Q), the combination of the amino acid insertions in the fingers and the T215Y mutation allows efficient excision of ddTMP and d4TMP, even when relatively high levels of deoxynucleoside triphosphates are present in the reaction. 2002 Journal of virology Abstract HIV M41L;D67N;K70R;T215Y;F219E;K219E;T215Y 54;59;64;69;78;78;161 58;63;68;74;85;85;166 12186898 Nucleoside analog resistance caused by insertions in the fingers of human immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated excision. RT variants with the amino acid insertions in the fingers and T215Y have a decreased level of misincorporation of ddATP and 3TCTP. 2002 Journal of virology Abstract HIV T215Y 62 67 RT 0 2 12186898 Nucleoside analog resistance caused by insertions in the fingers of human immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated excision. We have proposed that the T215F/Y mutation makes the binding of ATP to HIV-1 RT more effective, which increases the excision of 3-azido-3'-deoxythymidine-5'-monophosphate (AZTMP) in vitro and increases zidovudine (AZT) resistance in vivo. 2002 Journal of virology Abstract HIV T215F;T215Y 26;26 33;33 RT 77 79 12187506 Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts. Although D30N confers little or no cross-resistance to other protease inhibitors (PIs) and has been shown to allow effective substitution of a second PI, L90M with secondary mutations is involved in broad cross-resistance to the class. 2002 HIV clinical trials Abstract HIV D30N;L90M 9;154 13;158 PR;PI;PI 61;82;150 69;85;152 12187506 Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts. Although L90M has been observed rarely to date under nelfinavir selection, data on the relative incidence of these two mutations on failure of first-line nelfinavir HAART are sparse. 2002 HIV clinical trials Abstract HIV L90M 9 13 12187506 Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts. BACKGROUND: Both D30N and L90M in HIV-1 protease are primary resistance mutations that emerge under nelfinavir drug pressure. 2002 HIV clinical trials Abstract HIV D30N;L90M 17;26 21;30 PR 40 48 12187506 Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts. CONCLUSION: Almost 95% of failures on first-line nelfinavir-based triple-drug HAART occur without PI mutations or with D30N as the primary protease change. 2002 HIV clinical trials Abstract HIV D30N 119 123 PR;PI 139;98 147;100 12187506 Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts. D30N and L90M (+/- secondary mutations) occurred in 30.7% and 4.8%, respectively. 2002 HIV clinical trials Abstract HIV L90M;D30N 9;0 13;4 12187506 Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts. L90M occurs in only 5% of cases. 2002 HIV clinical trials Abstract HIV L90M 0 4 12194983 The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using alpha-boranophosphate nucleotide analogues. The appearance of up to five substitutions (A62V, V75I, F77L, F116Y, and Q151M) in the viral reverse transcriptase promotes resistance to these drugs, and reduces efficiency of the antiretroviral chemotherapy. 2002 The Journal of biological chemistry Abstract HIV A62V;F116Y;F77L;Q151M;V75I 44;62;56;73;50 48;67;60;78;54 RT 93 114 12194983 The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using alpha-boranophosphate nucleotide analogues. Using A62V/V75I/F77L/F116Y/Q151M RT, k(pol) increases up to 70- and 13-fold using alpha-boranophosphate-ddATP and alpha-boranophosphate AZTTP, respectively. 2002 The Journal of biological chemistry Abstract HIV A62V;F116Y;F77L;Q151M;V75I 6;21;16;27;11 10;26;20;32;15 Pol;RT 39;33 42;35 12194983 The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using alpha-boranophosphate nucleotide analogues. Using pre-steady state kinetics, we show that Q151M and A62V/V75I/F77L/F116Y/Q151M substitutions confer to reverse transcriptase (RT) the ability to discriminate an analogue relative to its natural counterpart, and have no effect on repair of the analogue-terminated DNA primer. 2002 The Journal of biological chemistry Abstract HIV A62V;F116Y;F77L;Q151M;V75I;Q151M 56;71;66;77;61;46 60;76;70;82;65;51 RT;RT 107;130 128;132 12195348 Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial. No differences were observed in the frequency of development of resistance mutations L90M (P=1.00) and D30N (P=.61) in B and non-B viruses. 2002 The Journal of infectious diseases Abstract HIV D30N;L90M 103;85 107;89 12196820 [HIV-1 integrase enzyme linked immunosorbent assay and inhibitors]. METHODS: HIV recombinant plasmid F185K/C280S IN1-288 was transformed into the E.coli strain BL21(DE3) integrase with a histag was induced by adding isopropyl-?-D?thiogalactopyranoside (IPTG)and purified by nickel affinity chromatography. 2002 Zhonghua shi yan he lin chuang bing du xue za zhi Abstract HIV C280S;F185K 39;33 44;38 IN;IN 102;45 111;48 12200006 [Genotypic resistance of human immunodeficiency virus in patients with virologic failure]. RESULTS: Mutations were observed in 52,6% of cases for reverse transcriptase (RT) an in 81,8% for the protease genes, being T215Y and V82A the most frequently detected ones. 2002 Medicina clinica Abstract HIV T215Y;V82A 124;134 129;138 RT;PR;RT 55;102;78 76;110;80 12200452 Exploring the effects of active site constraints on HIV-1 reverse transcriptase DNA polymerase fidelity. By increasing the steric demand the effects on RT(M184V) in comparison with RT(WT) become progressively more pronounced. 2002 The Journal of biological chemistry Abstract HIV M184V 50 55 RT;RT 47;76 49;78 12200452 Exploring the effects of active site constraints on HIV-1 reverse transcriptase DNA polymerase fidelity. Introduction of a methyl group reduces the maximum rate of nucleotide incorporation by about 200-fold for RT(WT) and about 400-fold for RT(M184V). 2002 The Journal of biological chemistry Abstract HIV M184V 139 144 RT;RT 106;136 108;138 12200452 Exploring the effects of active site constraints on HIV-1 reverse transcriptase DNA polymerase fidelity. This results in relative incorporation efficiencies [(k(pol)/K(d))(incorrect)/(k(pol)/K(d))(TTPcorrect)] of 4.1 x 10(-5) for TTP and 3.4 x 10(-6) for T(Me)TP in case of RT(WT) and 1.4 x 10(-5) for TTP and 2.9 x 10(-8) for T(Me)TP in case of RT(M184V). 2002 The Journal of biological chemistry Abstract HIV M184V 244 249 Pol;Pol;RT;RT 56;81;169;241 59;84;171;243 12201905 Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure. No virological response was observed in six patients harboring a single Y181C/I mutation. 2002 AIDS research and human retroviruses Abstract HIV Y181C;Y181I 72;72 79;79 12206668 Mutations in the ribonuclease H active site of HIV-RT reveal a role for this site in stabilizing enzyme-primer-template binding. We examined the effect of RNase H deficient E(478)-->Q and D(549)-->N mutations that do not alter polymerase activity on binding of enzyme to various nucleic acid substrates. 2002 Biochemistry Abstract HIV D549N;E478Q 56;41 72;57 Pol 98 108 12208978 Crystal structures of Zidovudine- or Lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41, 184, and 215. Minimal conformational changes in the polymerase or nonnucleoside RT inhibitor sites compared to the mutant RTMC (D67N, K70R, T215F, and K219N) are observed, indicating that such changes may occur only with certain combinations of mutations. 2002 Journal of virology Abstract HIV D67N;K219N;K70R;T215F 114;137;120;126 118;142;124;131 Pol;RT 38;66 48;68 12208978 Crystal structures of Zidovudine- or Lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41, 184, and 215. Model building M41L and T215Y into HIV-1 RT-DNA and docking in ATP that is utilized in the pyrophosphorolysis reaction for AZT resistance indicates that some conformational rearrangement appears necessary in RT for ATP to interact simultaneously with the M41L and T215Y mutations. 2002 Journal of virology Abstract HIV M41L;M41L;T215Y;T215Y 15;255;24;264 19;259;29;269 RT;RT 41;208 43;210 12208978 Crystal structures of Zidovudine- or Lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41, 184, and 215. Six structures of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing combinations of resistance mutations for zidovudine (AZT) (M41L and T215Y) or lamivudine (M184V) have been determined as inhibitor complexes. 2002 Journal of virology Abstract HIV M184V;M41L;T215Y 190;159;168 195;164;173 RT;RT 62;85 83;87 12209315 Analysis of conserved and non-conserved amino acids critical for ALSV (Avian leukemia and sarcoma viruses) integrase functions in vitro. We found that (i) 88% of the substitutions occurring on well-conserved residues have an effect on IN activities (ii) two mutants (S85T in the central catalytic domain and N197C in the C-terminal domain) present a reduced efficiency of DNA binding compared to the wild type protein. 2002 Archives of virology Abstract HIV N197C;S85T 171;130 176;135 IN 98 100 12212925 A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma. Compared to WT, MNR HIV-1 RT had 5- to 36-fold increases in the concentration of drug required to inhibit 50% (IC50) of RT activity, depending on the presence of Q151 M alone or with additional MNR mutations. 2002 Antiviral therapy Abstract HIV Q151M 162 168 RT;RT 26;120 28;122 12212925 A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma. In contrast, 21 specimens were sensitive to zidovudine-TP, of which 12 had WT genotypes, four had T215Y/F, and five had T69S-insertions along with T215Y/F mutations. 2002 Antiviral therapy Abstract HIV T215F;T215F;T215Y;T215Y;T69S 98;147;98;147;120 105;154;105;154;124 12212925 A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma. This assay exploits the different biochemical mechanisms for zidovudine-resistance conferred by either Q151 M or T215Y/F mutations and the inability of conventional RT assays to detect T215Y/F-associated zidovudine resistance. 2002 Antiviral therapy Abstract HIV Q151M;T215F;T215F;T215Y;T215Y 103;113;185;113;185 109;120;192;120;192 RT 165 167 12212925 A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma. This RT-based phenotypic assay provides a specific and rapid tool for the direct identification and monitoring of Q151M-associated MNR HIV-1 in plasma. 2002 Antiviral therapy Abstract HIV Q151M 114 119 RT 5 7 12212925 A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma. Twenty-three specimens were found to have reduced susceptibility to zidovudine-TP, and all had Q151 M. 2002 Antiviral therapy Abstract HIV Q151M 95 101 12212925 A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma. We show that enzymatic resistance to zidovudine-TP is specific to MNR RT and is distinguishable from both wild-type (WT) and RT containing classical zidovudine-resistant mutations (D67N, K70R, T215Y/F, K219Q). 2002 Antiviral therapy Abstract HIV D67N;K219Q;K70R;T215F;T215Y 181;202;187;193;193 185;207;191;200;200 RT;RT 70;125 72;127 12212925 A rapid phenotypic assay for detecting multiple nucleoside analogue reverse transcriptase inhibitor-resistant HIV-1 in plasma. Zidovudine and other nucleoside analogue reverse transcriptase inhibitors (NRTIs), like zalcitabine and didanosine used for treatment of individuals infected with HIV-1, can select for viruses with Q151M and other associated mutations (for example, A62V, S68G, V751, F77L, F116Y) in the reverse transcriptase (RT) enzyme. 2002 Antiviral therapy Abstract HIV A62V;F116Y;F77L;Q151M;S68G 249;273;267;198;255 253;278;271;203;259 NRTI;RT;NRTI;RT 21;287;75;310 62;308;80;312 12218942 Resistance mutations in HIV-infected patients experiencing early failure with nelfinavir-containing triple combinations. All six individuals harbored the D30N mutation, and none presented the L90M mutation. 2002 Medical science monitor Abstract HIV D30N;L90M 33;71 37;75 12218942 Resistance mutations in HIV-infected patients experiencing early failure with nelfinavir-containing triple combinations. By contrast, mutations conferring resistance to reverse transcriptase inhibitors were present in 50% of the patients, and the M184V substitution was the most frequently seen. 2002 Medical science monitor Abstract HIV M184V 126 131 RT 48 69 12218942 Resistance mutations in HIV-infected patients experiencing early failure with nelfinavir-containing triple combinations. The D30N substitution, rather than L90M, is the most frequently recognized, which does not challenge the efficacy of further rescue interventions with other PIs. 2002 Medical science monitor Abstract HIV D30N;L90M 4;35 8;39 PI 157 160 12237461 Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutations. Here, we perform multinanosecond molecular dynamics simulations on L63P HIV-1 PR, corresponding to the wild type, and one of its most frequently occurring compensatory mutations, M46I, complexed with the substrate and an enzymatic intermediate. 2002 Protein science Abstract HIV L63P;M46I 67;179 71;183 PR 78 80 12239335 Insertions in the reverse transcriptase increase both drug resistance and viral fitness in a human immunodeficiency virus type 1 isolate harboring the multi-nucleoside reverse transcriptase inhibitor resistance 69 insertion complex mutation. However, in the absence of drug, the virus with the RT from the original clinical isolate (SS) was more fit than (i) the wild-type virus with an engineered serine insertion between residues 69 and 70 (T69SSS) and (ii) the recombinant virus with the MNR RT where the insertion was removed (2S0S). 2002 Journal of virology Abstract HIV T69SSS 201 207 RT;RT 52;253 54;255 12350353 Human immunodeficiency virus type 1 reverse transcription is stimulated by tat from other lentiviruses. We mutated the homologous position in jTat to H62Y and found it did not improve its ability to stimulate reverse transcription, but an H62A mutation did inhibit jTat complementation. 2002 Virology Abstract HIV H62A;H62Y 135;46 139;50 RT 105 126 12367650 Novel mutations in the thymidine kinase and DNA polymerase genes of acyclovir and foscarnet resistant herpes simplex viruses infecting an immunocompromised patient. The foscarnet resistance was associated with an S725G mutation in a conserved region (region II) of the herpesvirus DNA pol gene. 2002 Journal of clinical virology Abstract HIV S725G 48 53 Pol 120 123 12367719 Polymorphisms of cytotoxic T-lymphocyte (CTL) and T-helper epitopes within reverse transcriptase (RT) of HIV-1 subtype C from Ethiopia and Botswana following selection of antiretroviral drug resistance. Mutations within immunogenic regions of clade C RT were noted during drug selection of subtype C isolates with nevirapine (S98I, Y181C, V108I and K103N), delavirdine, (A62V, V75E, L100I, K103T, V108I, Y181C), efavirenz (K103E, V106M, V179D, Y188C/H, G190A), lamivudine (M184I, M184V), and zidovudine (K70R), respectively. 2002 Antiviral research Abstract HIV A62V;G190A;K103E;K103N;K103T;K70R;L100I;M184I;M184V;S98I;V106M;V108I;V108I;V179D;V75E;Y181C;Y181C;Y188C;Y188H 168;250;220;146;187;301;180;270;277;123;227;136;194;234;174;129;201;241;241 172;255;225;151;192;305;185;275;282;127;232;141;199;239;178;134;206;248;248 RT 48 50 12367727 Rapid phenotypic assay for human immunodeficiency virus type 1 protease using in vitro translation. Three drug-resistant proteases carrying a single mutation, D30N, L90M, and V82F, were analyzed in the absence of the inhibitors. 2002 Journal of virological methods Abstract HIV D30N;L90M;V82F 59;65;75 63;69;79 PR 21 30 12367727 Rapid phenotypic assay for human immunodeficiency virus type 1 protease using in vitro translation. Using the Gag-Pol substrate as the target, the indinavir-resistant mutant V82F was evaluated further. 2002 Journal of virological methods Abstract HIV V82F 74 78 GagPol 10 17 12367727 Rapid phenotypic assay for human immunodeficiency virus type 1 protease using in vitro translation. V82F showed 9-fold resistance to its cognitive protease inhibitor, indinavir; however, it manifested only moderate (2-fold) resistance to a non-cognitive inhibitor, nelfinavir. 2002 Journal of virological methods Abstract HIV V82F 0 4 PR 47 55 12368302 Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. Based on these results, we conclude that HIV-1(V165A) and HIV-1(R166A) are pleiotropic mutants primarily defective for IN catalysis and that Val-165 and Arg-166 do not play a specific role in the nuclear localization of HIV-1 PICs in infected cells. 2002 Journal of virology Abstract HIV R166A;V165A 64;47 69;52 IN 119 121 12368302 Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. First, results of transient transfections revealed that V165A FLAG-tagged IN and green fluorescent protein-IN fusions carrying either V165A or R166A predominantly localized to cell nuclei. 2002 Journal of virology Abstract HIV R166A;V165A;V165A 143;56;134 148;61;139 IN;IN 74;107 76;109 12368302 Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. In this study we confirmed that HIV-1(V165A) and HIV-1(R166A) were replication defective and that less mutant viral cDNA localized to infected cell nuclei. 2002 Journal of virology Abstract HIV R166A;V165A 55;38 60;43 12368302 Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. Second, two different strains of previously described class II IN mutant viruses displayed similar nuclear entry profiles to those observed for HIV-1(V165A) and HIV-1(R166A), suggesting that defective nuclear import may be a common phenotype of replication-defective IN mutant viruses. 2002 Journal of virology Abstract HIV R166A;V165A 167;150 172;155 IN;IN 63;267 65;269 12368302 Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import. Third, V165A and R166A mutants were defective for in vitro integration activity, when assayed both as PICs isolated from infected T-cells and as recombinant IN proteins purified from Escherichia coli. 2002 Journal of virology Abstract HIV R166A;V165A 17;7 22;12 IN 157 159 12368324 The Mason-Pfizer monkey virus internal scaffold domain enables in vitro assembly of human immunodeficiency virus type 1 Gag. Despite the dramatic effect of the ISD on chimera assembly, the function of HIV Gag domains in that process was found to remain essential, since an assembly-defective mutant of HIV CA, M185A, abolished assembly when introduced into the chimera. 2002 Journal of virology Abstract HIV M185A 185 190 Gag;Capsid 80;181 83;183 12368352 Evolution of phenotypic drug susceptibility and viral replication capacity during long-term virologic failure of protease inhibitor therapy in human immunodeficiency virus-infected adults. The emergence of primary genotypic mutations within protease (particularly V82A, I84V, and L90M) was temporally associated with increasing phenotypic resistance and decreasing replicative capacity, while the emergence of secondary mutations within protease was associated with more-gradual changes in both phenotypic resistance and replicative capacity. 2002 Journal of virology Abstract HIV I84V;L90M;V82A 81;91;75 85;95;79 PR;PR 52;248 60;256 12370512 The prevalence and determinants of the K65R mutation in HIV-1 reverse transcriptase in tenofovir-naive patients. The K65R mutation in HIV-1 reverse transcriptase is associated with reduced susceptibility to abacavir and tenofovir. 2002 AIDS (London, England) Abstract HIV K65R 4 8 RT 27 48 12370512 The prevalence and determinants of the K65R mutation in HIV-1 reverse transcriptase in tenofovir-naive patients. The presence of K65R is associated with previous abacavir use. 2002 AIDS (London, England) Abstract HIV K65R 16 20 12376953 Persistence of earlier HIV-1 drug resistance mutations at new treatment failure. After changing from zidovudine- to stavudine-containing regimens, the thymidine analogue mutations (especially M41L and T215Y/F) were found at new treatment failure in almost all patients. 2002 Journal of medical virology Abstract HIV M41L;T215F;T215Y 111;120;120 115;127;127 12376953 Persistence of earlier HIV-1 drug resistance mutations at new treatment failure. In contrast, after changing from indinavir to saquinavir or nelfinavir, the M46I/L and/or V82A/F/ST disappeared in only 9 of 21 occasions at the new treatment failure. 2002 Journal of medical virology Abstract HIV M46I;M46L;V82A;V82F;V82S;V82T 76;76;90;90;90;90 82;82;99;99;99;99 12376953 Persistence of earlier HIV-1 drug resistance mutations at new treatment failure. Most secondary mutations persisted with the exception of N88D. 2002 Journal of medical virology Abstract HIV N88D 57 61 12376953 Persistence of earlier HIV-1 drug resistance mutations at new treatment failure. The M184V mutation disappeared in most (64%) non-3TC treated patients, although it persisted in a few didanosine- and abacavir-treated subjects. 2002 Journal of medical virology Abstract HIV M184V 4 9 12383014 Stereoselective synthesis and antiviral activity of D-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides. Molecular modeling studies demonstrated that the larger van der Waals radius as well as the close proximity to Met184 of the 4'-sulfur atom of D-2'-F-4'-Sd4C (17) may be the reasons for the decreased antiviral potency of synthesized 4'-thio nucleosides against the lamivudine-resistant variants (HIV-1(M184V)). 2002 Journal of medicinal chemistry Abstract HIV M184V 302 307 12383014 Stereoselective synthesis and antiviral activity of D-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides. The cytidine 17 and 5-fluorocytidine 18 analogues showed significantly decreased antiviral activity against the clinically important lamivudine-resistant variants (HIV-1(M184V)), whereas the corresponding D-2'-Fd4 nucleosides showed limited cross-resistance. 2002 Journal of medicinal chemistry Abstract HIV M184V 170 175 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. ATP-mediated removal of carbovir as well as small increases in the inhibitory capacity of carbovir appear to contribute to the resistance of mutants with the K65R mutation and the mutants with the K65R and M184V mutations to abacavir. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;M184V 158;197;206 162;201;211 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Enzymatic and viral replication analyses were undertaken to elucidate the mechanisms of altered drug susceptibilities and potential fitness defects for the K65R and K65R+M184V mutants. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;M184V 156;165;170 160;169;175 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Finally, both the HIV-1 K65R mutant and, more notably, the HIV-1 K65R+M184V double mutant showed reduced replication capacities and reduced RT processivities in vitro, consistent with a potential fitness defect in vivo and the low prevalence of the K65R mutation among isolates from antiretroviral agent-experienced patients. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V;K65R 249;70;65 253;75;69 RT 140 142 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. For the mutant viruses with the K65R and M184V mutations, the increase in tenofovir susceptibility compared to that of the mutants with K65R correlated with a decrease in the tenofovir inhibitory capacity that was mediated primarily by an increased K(m) of dATP. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;M184V 32;136;41 36;140;46 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) resistance mutations K65R and M184V result in changes in susceptibility to several nucleoside and nucleotide RT inhibitors. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V 92;101 96;106 RT;RT;RT 44;67;180 65;69;182 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. K65R-containing viruses showed decreases in susceptibility to tenofovir, didanosine (ddI), abacavir, and (-)-beta-D-dioxolane guanosine (DXG; the active metabolite of amdoxovir) but appeared to be fully susceptible to zidovudine and stavudine in vitro. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R 0 4 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. The decrease in susceptibility to ddI by mutants with the K65R and M184V mutations correlated with an increase in the inhibitory capacity mediated by an increased K(i). 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V 58;67 62;72 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. The relative inhibitory capacities (K(i)/K(m)) of the active metabolites of tenofovir, ddI, and DXG were increased for the RT containing the K65R mutation compared to that for the wild-type RT, but the relative inhibitory capacity of abacavir was only minimally increased. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R 141 145 RT;RT 123;190 125;192 12384348 Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Viruses containing the K65R and M184V mutations showed further decreases in susceptibility to ddI and abacavir but increased susceptibility to tenofovir compared to the susceptibilities of viruses with the K65R mutation. 2002 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;M184V 23;206;32 27;210;37 12385703 Development of drug resistance in HIV-1 patients receiving a combination of stavudine, lamivudine and efavirenz. Results showed that viruses carrying primary mutations, usually K103N, T215Y and M41L, presented higher levels of HIV-1 RNA, suggesting an association between a precise mutation pattern and treatment failure. 2002 International journal of antimicrobial agents Abstract HIV K103N;M41L;T215Y 64;81;71 69;85;76 12388733 Characterization of a putative alpha-helix across the capsid-SP1 boundary that is critical for the multimerization of human immunodeficiency virus type 1 gag. Further analysis in the context of the protease-negative mutation D185H confirmed the key roles of amino acids H359, A361, L364, and M368 in virus assembly. 2002 Journal of virology Abstract HIV D185H 66 71 PR 39 47 12388733 Characterization of a putative alpha-helix across the capsid-SP1 boundary that is critical for the multimerization of human immunodeficiency virus type 1 gag. Importantly, when transfected cells were subjected to Dounce homogenization and the cell lysates were treated by ultracentrifugation at 100,000 x g, Gag molecules containing each of the H359A, A361V, L364A, and M368A mutations were found mainly in the supernatant fraction (S100), whereas approximately 80% of wild-type Gag proteins were found in the pellet. 2002 Journal of virology Abstract HIV A361V;H359A;L364A;M368A 193;186;200;211 198;191;205;216 Gag;Gag 149;320 152;323 12388733 Characterization of a putative alpha-helix across the capsid-SP1 boundary that is critical for the multimerization of human immunodeficiency virus type 1 gag. Notably, changes of the two basic amino acids H359 and K360 to arginine (R) impaired virus production, whereas mutations L364I and M368I, in contrast to L364A and M368A, generated near-wild-type levels of virus particles. 2002 Journal of virology Abstract HIV L364A;L364I;M368A;M368I 153;121;163;131 158;126;168;136 12396453 Genotypic and phenotypic cross-resistance patterns to lopinavir and amprenavir in protease inhibitor-experienced patients with HIV viremia. Mutations L10I (RI, 1.7), M46I (RI, 2.3), and L90M (RI, 1.9, but 65% linked with the I84V) were associated with decreased APV susceptibility in the univariate analysis (p < 0.001). 2002 AIDS research and human retroviruses Abstract HIV I84V;L10I;L90M;M46I 85;10;46;26 89;14;50;30 12396453 Genotypic and phenotypic cross-resistance patterns to lopinavir and amprenavir in protease inhibitor-experienced patients with HIV viremia. Mutations L10I, G48V, I54T, I54V, and V82A were significantly associated with decreased LPV susceptibility (p < 0.001 for each) and had increased RIs of 2.2, 4.4, 13, 4.6, and 3.2, respectively. 2002 AIDS research and human retroviruses Abstract HIV G48V;I54T;I54V;L10I;V82A 16;22;28;10;38 20;26;32;14;42 12396453 Genotypic and phenotypic cross-resistance patterns to lopinavir and amprenavir in protease inhibitor-experienced patients with HIV viremia. The I84V mutation was the strongest APV resistance marker in PI-experienced subjects in both univariate and multivariate analyses, with an increased relative incidence (RI) of 6.9 with >2.5 FR. 2002 AIDS research and human retroviruses Abstract HIV I84V 4 8 PI 61 63 12406504 Interactions of enantiomers of 2',3'-didehydro-2',3'-dideoxy-fluorocytidine with wild type and M184V mutant HIV-1 reverse transcriptase. Molecular modeling suggests that L- and D-D4FC-TP are positioned in the active site favorably for incorporation by RT(WT) and that L-D4FC-TP, but not D-D4FC-TP, is sterically hindered by the addition of a beta branched amino acid at position 184 of RT(M184V). 2002 Antiviral research Abstract HIV M184V 252 257 RT;RT 115;249 117;251 12406504 Interactions of enantiomers of 2',3'-didehydro-2',3'-dideoxy-fluorocytidine with wild type and M184V mutant HIV-1 reverse transcriptase. The kinetic parameters of incorporation in the presence of L-D4FC-TP by RT(WT) and the mechanism of resistance by RT(M184V) were found to be distinct from those seen with the corresponding L-isomers containing an oxathiolane ring: (-)-3TC-TP and (-)-FTC-TP. 2002 Antiviral research Abstract HIV M184V 117 122 RT;RT 72;114 74;116 12406504 Interactions of enantiomers of 2',3'-didehydro-2',3'-dideoxy-fluorocytidine with wild type and M184V mutant HIV-1 reverse transcriptase. While no resistance was conferred by the methionine 184 to valine mutation to D-D4FC-TP, L-D4FC-TP was incorporated 50- to 70-fold less efficiently. 2002 Antiviral research Abstract HIV M184V 41 65 12435689 Mutagenically separated PCR assay for rapid detection of M41L and K70R zidovudine resistance mutations in CRF01_AE (subtype E) human immunodeficiency virus type 1. A rapid zidovudine (ZDV) resistance genotypic assay was developed based on the mutagenically separated PCR (MS-PCR) technique to detect two ZDV-resistant mutations, M41L and K70R in CRF01_AE (subtype E). 2002 Antimicrobial agents and chemotherapy Abstract HIV K70R;M41L 174;165 178;169 12436471 Replication capacity, biological phenotype, and drug resistance of HIV strains isolated from patients failing antiretroviral therapy. The highest replication capacity was observed in strains carrying the K103N and Y181C primary mutations that emerged after treatment with non-nucleoside analogue inhibitors. 2003 Journal of medical virology Abstract HIV K103N;Y181C 70;80 75;85 12441810 Emergence of drug-resistant HIV-1 variants in patients undergoing structured treatment interruptions. THe protease mutations K101E and K103N were detected at the end of the second or third STI. 2002 AIDS (London, England) Abstract HIV K101E;K103N 23;33 28;38 PR 4 12 12454144 Testing genotypic and phenotypic resistance in human immunodeficiency virus type 1 isolates of clade B and other clades from children failing antiretroviral therapy. Prevalence of known drug resistance mutations revealed slightly significant differences among B and non-B subtypes: L10I, 21 and 64%, K20R, 13 and 43%, M36I, 34 and 100%, L63P, 76 and 36%, A71V/T, 24 and 0%, and V77I, 32 and 0%, respectively, in the protease (0.0001 or = F61L > wild-type = F61A > F61W. 2003 Journal of molecular biology Abstract HIV F61A;F61L;F61W;F61Y 221;202;228;190 225;206;232;194 RT 23 26 12498795 Substitutions at Phe61 in the beta3-beta4 hairpin of HIV-1 reverse transcriptase reveal a role for the Fingers subdomain in strand displacement DNA synthesis. While the strand displacement activity of F61W RT variant was affected severely, it displayed a wild-type-like processivity. 2003 Journal of molecular biology Abstract HIV F61W 42 46 RT 47 49 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. 150 out of 223 clinical samples had the M184V mutation. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 40 45 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. A 2.4- or 8-fold increase in ZDV-R was observed in the clinical samples with high ZDV-R containing the R211K/L214F or H208Y/R211K/L214F mutations, respectively. 2003 Antimicrobial agents and chemotherapy Abstract HIV H208Y;L214F;R211K;L214F;R211K 118;130;124;109;103 123;135;129;114;108 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. A comparable correlation was obtained when ZDV-R was analyzed only relative to the T215Y/F mutation. 2003 Antimicrobial agents and chemotherapy Abstract HIV T215F;T215Y 83;83 90;90 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. All changes were independent of the M184V mutation. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 36 41 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. In addition, enhanced resistance to ZDV in the context of the classic ZDV mutations plus the M184V mutation has been associated with additional mutations at positions 208, 211, 214, and 333. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 93 98 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. In the clinical sample data set we analyzed, the combination of R211K/L214F appeared most frequently. 2003 Antimicrobial agents and chemotherapy Abstract HIV L214F;R211K 70;64 75;69 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. Site-directed mutagenesis experiments investigating the influence of the additional mutations H208Y, R211K, and L214F on ZDV-R resulted in a 7.4- or 21-fold increase in ZDV-R when the R211K/L214F or H208Y/R211K/L214F mutations, respectively, were added to a highly ZDV-R virus. 2003 Antimicrobial agents and chemotherapy Abstract HIV H208Y;L214F;R211K;H208Y;L214F;L214F;R211K;R211K 199;211;205;94;190;112;101;184 204;216;210;99;195;117;106;189 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. The H208Y change was detected only in highly ZDV-R viruses, whereas the G333E/D change was distributed equally. 2003 Antimicrobial agents and chemotherapy Abstract HIV G333D;G333E;H208Y 72;72;4 79;79;9 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. We have shown that the combination of the additional mutations H208Y, R211K, and L214F in HIV-1 RT may influence ZDV-R and should be considered when assessing ZDV-R. 2003 Antimicrobial agents and chemotherapy Abstract HIV H208Y;L214F;R211K 63;81;70 68;86;75 RT 96 98 12499169 Correlation of phenotypic zidovudine resistance with mutational patterns in the reverse transcriptase of human immunodeficiency virus type 1: interpretation of established mutations and characterization of new polymorphisms at codons 208, 211, and 214. Zidovudine resistance (ZDV-R) is associated with classic genotypic changes at codons 41, 67, 70, 210, 215, and 219 of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) gene as well as with the multinucleoside resistance (MNR) complexes (Q151M MNR complex; 6-bp insertion/A62V complex). 2003 Antimicrobial agents and chemotherapy Abstract HIV A62V;Q151M 296;262 300;268 RT;RT 166;189 187;191 12501127 Safety and pharmacokinetic profile of multiple escalating doses of (+)-calanolide A, a naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy HIV-negative volunteers. BACKGROUND: (+)-Calanolide A is a naturally occurring nonnucleoside reverse transciptase inhibitor (NNRTI) that exhibits enhanced activity against HIV-1 isolates with the Y181C mutation and retains activity against HIV-1 isolates with dual Y181C and K103N mutations. 2002 HIV clinical trials Abstract HIV K103N;Y181C;Y181C 250;171;240 255;176;245 NNRTI 100 105 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. A site-directed mutant of SIVmac239 containing M184V (SIVmac239-184V) was used to select for resistance to both 3TC and PMPA by serial passage in the presence of increasing concentrations of both drugs. 2003 Journal of virology Abstract HIV M184V 47 52 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. All animals receiving this combination developed the K65R mutation. 2003 Journal of virology Abstract HIV K65R 53 57 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. Similarly, in rhesus macaques infected with SIVmac239-184V for 46 weeks and treated daily with (-)-2'-deoxy-5-fluoro-3'-thiacytidine [(-)-FTC], there was no reversion of M184V, but this mutation reverted to 184 M in all three animals within 24 weeks of treatment with (-)-FTC and PMPA. 2003 Journal of virology Abstract HIV M184V 170 175 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. The methionine-to-valine mutation in codon 184 (M184V) in reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) confers resistance to (-)-2'-deoxy-3'-thiacytidine (3TC; lamivudine) and increased sensitivity to 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir). 2003 Journal of virology Abstract HIV M184V;M184V 48;4 53;46 RT;RT 58;81 79;83 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. These results demonstrate that the combination of PMPA with 3TC or (-)-FTC selects for the K65R mutation and against the M184V mutation in SIV RT. 2003 Journal of virology Abstract HIV K65R;M184V 91;121 95;126 RT 143 145 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. Under these selection conditions, the M184V mutation reverted in the majority of the selections. 2003 Journal of virology Abstract HIV M184V 38 43 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. Variants resistant to both drugs were found to have the lysine-to-arginine mutation at codon 65 (K65R), which has previously been associated with resistance to PMPA in both SIV and HIV. 2003 Journal of virology Abstract HIV K65R;K65R 97;56 101;95 12502828 Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. We have used the SIV model to evaluate the effect of the M184V mutation on the emergence of resistance to the combination of 3TC plus PMPA. 2003 Journal of virology Abstract HIV M184V 57 62 12502847 Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy. One of the first drug-resistant mutations to arise in the protease, particularly in patients receiving indinavir or ritonavir treatment, is V82A, which compromises the binding of these and other inhibitors but allows the virus to remain viable. 2003 Journal of virology Abstract HIV V82A 140 144 PR 58 66 12502847 Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy. The V82A mutation compromises these interactions with the drugs while not greatly affecting the substrate interactions, which is consistent with previously published kinetic data. 2003 Journal of virology Abstract HIV V82A 4 8 12502847 Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy. To probe this drug resistance, we solved the crystal structures of three natural substrates and two commercial drugs in complex with an inactive drug-resistant mutant (D25N/V82A) HIV-1 protease. 2003 Journal of virology Abstract HIV D25N;V82A 167;173 172;177 PR 185 193 12502862 Human immunodeficiency virus type 1 nucleocapsid zn(2+) fingers are required for efficient reverse transcription, initial integration processes, and protection of newly synthesized viral DNA. To examine replication defects, viral DNA (vDNA) was isolated from cells infected with viruses containing His-to-Cys changes in their Zn(2+) fingers (NC(H23C) and NC(H44C)), an integrase mutant (IN(D116N)), a double mutant (NC(H23C)/IN(D116N)), or wild-type HIV-1. 2003 Journal of virology Abstract HIV D116N;D116N;H23C;H23C;H44C 198;236;153;227;166 203;241;157;231;170 IN;IN;IN;NC;NC;NC 177;195;233;150;163;224 186;197;235;152;165;226 12507757 Membrane structure of the human immunodeficiency virus gp41 fusion peptide by molecular dynamics simulation. II. The glycine mutants. In fact, hydrogen bonding in this motif was found to be missing in FP-G3V and FP-G5V. 2003 Biochimica et biophysica acta Abstract HIV G3V;G5V 70;81 73;84 12507757 Membrane structure of the human immunodeficiency virus gp41 fusion peptide by molecular dynamics simulation. II. The glycine mutants. In this work, molecular dynamics (MD) simulation of the interaction of three mutants, G3V, G5V and G10V, of the human immunodeficiency virus (HIV) gp41 16-residue fusion peptide (FP) with an explicit palmitoyloleoylphosphatidyl-ethanolamine (POPE) lipid bilayer was performed. 2003 Biochimica et biophysica acta Abstract HIV G10V;G3V;G5V 99;86;91 103;89;94 gp41 147 151 12507757 Membrane structure of the human immunodeficiency virus gp41 fusion peptide by molecular dynamics simulation. II. The glycine mutants. On the other hand, the inactive mutants FP-G10V, FP-L9R and FP-V2E do not have any conformational transitions except at either terminus and thus possess no conformational flexibility. 2003 Biochimica et biophysica acta Abstract HIV G10V;L9R;V2E 43;52;63 47;55;66 12507757 Membrane structure of the human immunodeficiency virus gp41 fusion peptide by molecular dynamics simulation. II. The glycine mutants. The active WT FP and its partially active mutants, G3V and G5V, all have significant conformational transitions at one of the glycine sites. 2003 Biochimica et biophysica acta Abstract HIV G3V;G5V 51;59 54;62 12507757 Membrane structure of the human immunodeficiency virus gp41 fusion peptide by molecular dynamics simulation. II. The glycine mutants. They occur at Gly(5) in FP-wt, at Gly(10) in FP-G5V and at Gly(13) in FP-G3V. 2003 Biochimica et biophysica acta Abstract HIV G3V;G5V 73;48 76;51 12523458 Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. In vitro, recombinant human immunodeficiency virus (HIV) expressing the K65R mutation showed a 3-4-fold increase in the 50% inhibitory concentrations of tenofovir when compared with wild type. 2003 Pharmacotherapy Abstract HIV K65R 72 76 12534275 A major role for a set of non-active site mutations in the development of HIV-1 protease drug resistance. This mutant protease contains 11 mutations, 10 of which are located outside the active site (L10I/M36I/S37D/M46I/R57K/L63P/A71V/G73S/L90M/I93L) and 1 within the active site (I84V). 2003 Biochemistry Abstract HIV L10I;A71V;G73S;I93L;L63P;L90M;M36I;M46I;R57K;S37D;I84V 93;123;128;138;118;133;98;108;113;103;174 97;127;132;142;122;137;102;112;117;107;178 PR 12 20 12534958 Drug resistance mutations and outcome of second-line treatment in patients with first-line protease inhibitor failure on nelfinavir-containing HAART. A pronounced accumulation of the secondary protease mutations N88D, M36I, and A71V/T was found, and D30N was strongly associated with N88D. 2003 HIV medicine Abstract HIV A71T;A71V;D30N;M36I;N88D;N88D 78;78;100;68;62;134 84;84;104;72;66;138 PR 43 51 12534958 Drug resistance mutations and outcome of second-line treatment in patients with first-line protease inhibitor failure on nelfinavir-containing HAART. CONCLUSION: In patients failing nelfinavir-containing HAART, D30N was detected frequently and L90M occasionally. 2003 HIV medicine Abstract HIV D30N;L90M 61;94 65;98 12534958 Drug resistance mutations and outcome of second-line treatment in patients with first-line protease inhibitor failure on nelfinavir-containing HAART. Of eight patients with N88D, seven also harboured D30N (P < 0.01). 2003 HIV medicine Abstract HIV D30N;N88D 50;23 54;27 12534958 Drug resistance mutations and outcome of second-line treatment in patients with first-line protease inhibitor failure on nelfinavir-containing HAART. Ten patients had D30N (38%), five patients had L90M (19%), two patients had V82A/F (8%) and two patients had M46I/L (8%). 2003 HIV medicine Abstract HIV D30N;L90M;M46I;M46L;V82A;V82F 17;47;109;109;76;76 21;51;115;115;82;82 12534958 Drug resistance mutations and outcome of second-line treatment in patients with first-line protease inhibitor failure on nelfinavir-containing HAART. Two patients had both D30N and L90M. 2003 HIV medicine Abstract HIV D30N;L90M 22;31 26;35 12540238 Synthesis, anti-HIV activity, and molecular mechanism of drug resistance of L-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides. However, the steric hindrance between the sugar moiety of the unnatural l-nucleoside and the side chains of Val184 of M184V RT in 3TC-resistant mutant HIV strains destabilizes the RT-nucleoside triphosphate complex, which causes the cross-resistance to 3TC (M184V mutant). 2003 Journal of medicinal chemistry Abstract HIV M184V;M184V 118;258 123;264 RT;RT 124;180 126;182 12540238 Synthesis, anti-HIV activity, and molecular mechanism of drug resistance of L-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides. The cytosine derivative 17 (beta-l-2'-F-4'-S-d4C), however, showed cross-resistance to a 3TC-resistant variant (HIV-1(M184V)). 2003 Journal of medicinal chemistry Abstract HIV M184V 118 123 12543665 Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients. Baseline PI resistance mutations (L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S, I84V) identified by univariate analysis and included in a genotypic score and APV C(min) at week 8 were predictive of the virological response at week 12. 2003 Antimicrobial agents and chemotherapy Abstract HIV E35D;I54V;I84V;K20M;K20R;L10F;L10I;L10V;L63P;R41K;V82A;V82F;V82S;V82T 52;64;88;44;44;34;34;34;70;58;76;76;76;76 56;68;92;50;50;42;42;42;74;62;86;86;86;86 PI 9 11 12543687 Lamivudine can exert a modest antiviral effect against human immunodeficiency virus type 1 containing the M184V mutation. Cell-free assays revealed that high concentrations of 3TC triphosphate (i.e., >100 micro M) could affect chain termination and/or inhibit purified reverse transcriptase containing the M184V substitution. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 184 189 RT 147 168 12543687 Lamivudine can exert a modest antiviral effect against human immunodeficiency virus type 1 containing the M184V mutation. Despite the fact that M184V encodes up to 1,000-fold resistance to 3TC, we asked whether this drug might still display some antiviral effect in regard to viruses containing this mutation. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 22 27 12543687 Lamivudine can exert a modest antiviral effect against human immunodeficiency virus type 1 containing the M184V mutation. Reverse transcriptases cloned from clinical isolates harboring M184V in the context of multidrug resistance had similar IC(50) values for 3TC triphosphate compared to reverse transcriptase containing only the M184V mutation. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V 63;209 68;214 RT;RT 0;167 22;188 12543687 Lamivudine can exert a modest antiviral effect against human immunodeficiency virus type 1 containing the M184V mutation. The M184V mutation in human immunodeficiency virus (HIV) reverse transcriptase is associated with high-level resistance to both (-)2',3'-dideoxy-3'-thiacytidine (3TC) and (-)2',3'-dideoxy-5-fluoro-3'-thiacytidine as well as low-level resistance to 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, and abacavir. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 4 9 RT 57 78 12543687 Lamivudine can exert a modest antiviral effect against human immunodeficiency virus type 1 containing the M184V mutation. These results suggest that viruses containing M184V can retain a higher degree of sensitivity to 3TC than previously assumed. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 46 51 12551997 Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from KwaZulu-Natal, South Africa: implications for vaccine and antiretroviral control strategies. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. 2003 Journal of virology Abstract HIV I93L 27 31 RT;PR 63;54 84;62 12553483 Genotypic and phenotypic resistance patterns in early-stage HIV-1-infected patients failing initial therapy with stavudine, didanosine and nevirapine. Finally, one patient (7%) had exclusively TAM mutations (M41L). 2002 Antiviral therapy Abstract HIV M41L 57 61 12553483 Genotypic and phenotypic resistance patterns in early-stage HIV-1-infected patients failing initial therapy with stavudine, didanosine and nevirapine. Four of these seven patients also had thymidine analogue-associated mutations (TAM) (T215Y/F [2/4], M41L [1/4], D67N [2/4] and K70R [1/4]). 2002 Antiviral therapy Abstract HIV D67N;K70R;M41L;T215F;T215Y 112;127;100;85;85 116;131;104;93;93 12553483 Genotypic and phenotypic resistance patterns in early-stage HIV-1-infected patients failing initial therapy with stavudine, didanosine and nevirapine. Seven patients (50%) had nevirapine resistance mutations (mainly K103N [4/7], Y181C/I [2/7], G190A/S [2/7] and V108I [1/7]) associated with phenotypic high-level resistance to nevirapine, delavirdine and efavirenz (nevirapine >47.4- to 58.1-fold, delavirdine >74.4- to 168.9-fold and efavirenz >56.0- to 347.2-fold). 2002 Antiviral therapy Abstract HIV G190A;G190S;K103N;V108I;Y181C;Y181I 93;93;65;111;78;78 100;100;70;116;85;85 12553485 Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial). Importantly, although in vitro, ABC selects for M184V as the first mutation, ABC did not select for M184V when combined with ZDV without 3TC. 2002 Antiviral therapy Abstract HIV M184V;M184V 48;100 53;105 12553485 Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial). NFV-resistant virus was selected slowly through D30N or L90M pathways, and selection of ZDV-resistant virus was rare. 2002 Antiviral therapy Abstract HIV D30N;L90M 48;56 52;60 12553485 Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial). Reduced phenotypic susceptibility to ABC only occurred in the 3TC+ABC arm and required K65R and/or L74V in addition to M184V. 2002 Antiviral therapy Abstract HIV K65R;L74V;M184V 87;99;119 91;103;124 12553486 Long-term virological outcome in patients infected with multi-nucleoside analogue-resistant HIV-1. Two sets of mutations: the Q151 M complex and the 69 insert, cause resistance to multiple nucleoside analogues. 2002 Antiviral therapy Abstract HIV Q151M 27 33 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? Collectively, these factors might explain the residual antiviral effect and clinical benefit observed with continued use of 3TC in combination therapy regimens following the emergence of M184V. 2002 AIDS reviews Abstract HIV M184V 187 192 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? However, several of these trials did not possess adequate statistical power to resolve whether or not continued use of 3TC provided actual benefit, nor were they specifically designed to test the M184V benefit hypothesis in prospective fashion. 2002 AIDS reviews Abstract HIV M184V 196 201 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? Indeed, the results of numerous controlled as well as observational clinical studies are suggestive of improved therapeutic outcome associated with continued usage of 3TC and maintenance of the M184V mutation. 2002 AIDS reviews Abstract HIV M184V 194 199 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? Interestingly, the presence of M184V is also associated with alteration of several mechanisms relating to RT function that include decreased RT processivity, reduced nucleotide-dependent primer unblocking, increased fidelity, hypersensitization to other NRTIs, impaired viral fitness, and delayed appearance of mutations in RT that are responsible for resistance to thymidine analogues. 2002 AIDS reviews Abstract HIV M184V 31 36 NRTI;RT;RT;RT 254;106;141;324 259;108;143;326 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? Might the M184V substitution in HIV-1 RT confer clinical benefit? The M184V substitution in HIV-1 RT develops rapidly following initiation of therapy with 3TC and confers high-level phenotypic resistance to this drug both in vitro and in vivo. 2002 AIDS reviews Abstract HIV M184V 70 75 RT;RT 38;98 40;100 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? The M184V substitution in HIV-1 RT develops rapidly following initiation of therapy with 3TC and confers high-level phenotypic resistance to this drug both in vitro and in vivo. 2002 AIDS reviews Abstract HIV M184V 4 9 RT 32 34 12555696 Might the M184V substitution in HIV-1 RT confer clinical benefit? There is a need for randomized clinical trials of this type in order to validate the potential benefit of maintenance of M184V and whether continued use of 3TC is the only means of attaining this objective. 2002 AIDS reviews Abstract HIV M184V 121 126 12559908 Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. Consistent with their dimerization defect, the W401A, W401L and W414L mutants were devoid of RT activity. 2003 Journal of molecular biology Abstract HIV W401A;W401L;W414L 47;54;64 52;59;69 RT 93 95 12559908 Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. Consistent with this observation, the K331A RT mutant was dimerization-defective. 2003 Journal of molecular biology Abstract HIV K331A 38 43 RT 44 46 12559908 Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. Introduction of tryptophan mutants into the bacterial expression vector pRT6H/NB-PROT showed that RTs containing W401A or W401L substitutions (but not W401F) and W414L were defective for dimerization in vitro. 2003 Journal of molecular biology Abstract HIV W401A;W401F;W401L;W414L 113;151;122;162 118;156;127;167 PR;RT 72;98 74;101 12559908 Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. The suppressors (T409I, D110G, V372A and I393M) also restored heterodimerization of bacterially expressed W401A subunits. 2003 Journal of molecular biology Abstract HIV D110G;I393M;T409I;V372A;W401A 24;41;17;31;106 29;46;22;36;111 12559908 Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. When introduced into the W401A mutant, T409I was able to restore RT activity to 50% of the wild-type level. 2003 Journal of molecular biology Abstract HIV T409I;W401A 39;25 44;30 RT 65 67 12571524 Nonnucleoside reverse transcriptase inhibitor resistance among antiretroviral-naive HIV-positive pregnant women. Another had the K103N mutation. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 16 21 12571524 Nonnucleoside reverse transcriptase inhibitor resistance among antiretroviral-naive HIV-positive pregnant women. One had the K103R mutation, which conferred phenotypic resistance to NNRTIs by 8.3-fold, warranting a change in the initial regimen. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103R 12 17 NNRTI 69 75 12571524 Nonnucleoside reverse transcriptase inhibitor resistance among antiretroviral-naive HIV-positive pregnant women. The primary mutation, G190S, conferring resistance to NNRTIs was present in 1 patient. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G190S 22 27 NNRTI 54 60 12572241 Prevalence of primary and secondary resistant mutations to antiretroviral drug in a population of Puerto Rican infected with HIV. For the NNRTI the most common mutation was K103N in 40% of the subjects and found to confer cross resistance to NVP, DLV and EFV. 2002 Puerto Rico health sciences journal Abstract HIV K103N 43 48 NNRTI 8 13 12572241 Prevalence of primary and secondary resistant mutations to antiretroviral drug in a population of Puerto Rican infected with HIV. Mutation frequencies to the NRTI ranged in appearance from as high as 54% (i.e., M184V) in the studied subjects to a low of less than 5% (i.e., M184I and V75T). 2002 Puerto Rico health sciences journal Abstract HIV M184I;M184V;V75T 144;81;154 149;86;158 NRTI 28 32 12577193 Overcoming resistance: virologic response to a salvage regimen with the combination of ritonavir plus indinavir. A significant blunted virologic response was observed only in isolates with more than 12 substitutions including the V82A (-0.75 vs. 2003 HIV clinical trials Abstract HIV V82A 117 121 12593657 Design, synthesis, SAR, and molecular modeling studies of acylthiocarbamates: a novel series of potent non-nucleoside HIV-1 reverse transcriptase inhibitors structurally related to phenethylthiazolylthiourea derivatives. Nevertheless, the title compounds retained low potency against HIV-1 strains carrying mutations (K103R, Y181C, and K103N/Y181C) responsible for NNRTI resistance. 2003 Journal of medicinal chemistry Abstract HIV K103N;K103R;Y181C;Y181C 115;97;121;104 120;102;126;109 NNRTI 144 149 12600647 Rates of transmission of antiretroviral drug resistant strains of HIV-1. L63P was the most frequently found mutation (46.3%). 2003 Journal of clinical virology Abstract HIV L63P 0 4 12600647 Rates of transmission of antiretroviral drug resistant strains of HIV-1. Moreover, both M41L and K70R, but not T215Y, occurred with significantly decreased frequency in the post 1995 samples. 2003 Journal of clinical virology Abstract HIV K70R;M41L;T215Y 24;15;38 28;19;43 12600647 Rates of transmission of antiretroviral drug resistant strains of HIV-1. Secondary mutations/polymorphisms were seen in the PR at position L10I/V, K20R, M36I, L63P, A71T/V, or V77I in 60%. 2003 Journal of clinical virology Abstract HIV A71T;A71V;K20R;L10I;L10V;L63P;M36I;V77I 92;92;74;66;66;86;80;103 98;98;78;72;72;90;84;107 PR 51 53 12600647 Rates of transmission of antiretroviral drug resistant strains of HIV-1. The distribution of the most common resistance mutations in the RT was as follows; M41L (8.5%) and T215Y (8.5%) and K70R (4.8%). 2003 Journal of clinical virology Abstract HIV K70R;M41L;T215Y 116;83;99 120;87;104 RT 64 66 12600647 Rates of transmission of antiretroviral drug resistant strains of HIV-1. The prevalence of mutations that conferred primary resistance to protease inhibitors (PIs) was only 0.8% at position V82I. 2003 Journal of clinical virology Abstract HIV V82I 117 121 PR;PI 65;86 73;89 12609852 Molecular dynamics studies of the wild-type and double mutant HIV-1 integrase complexed with the 5CITEP inhibitor: mechanism for inhibition and drug resistance. In the first simulation the wild-type IN was used, whereas in the second one the double mutation T66I/M154I, described to lead to drug resistance, was introduced in the protein. 2003 Biophysical journal Abstract HIV M154I;T66I 102;97 107;101 IN 38 40 12610164 Effects of dipeptide insertions between codons 69 and 70 of human immunodeficiency virus type 1 reverse transcriptase on primer unblocking, deoxynucleoside triphosphate inhibition, and DNA chain elongation. Finger insertion mutations of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (T69S mutations followed by various dipeptide insertions) have a multinucleoside resistance phenotype that can be explained by decreased sensitivity to deoxynucleoside triphosphate (dNTP) inhibition of the nucleotide-dependent unblocking activity of RT. 2003 Journal of virology Abstract HIV T69S 102 107 RT;RT;RT 74;97;351 95;99;353 12610164 Effects of dipeptide insertions between codons 69 and 70 of human immunodeficiency virus type 1 reverse transcriptase on primer unblocking, deoxynucleoside triphosphate inhibition, and DNA chain elongation. The additional presence of M41L and T215Y mutations increased unblocking activity for all three insertions, greatly reduced the sensitivity to dNTP inhibition, and resulted in defects in in vitro DNA chain elongation. 2003 Journal of virology Abstract HIV M41L;T215Y 27;36 31;41 12620807 Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. HIV containing the G140S mutation showed a delay in replication. 2003 Virology Abstract HIV G140S 19 24 12620807 Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. In this report, the effects of a glycine to serine mutation at position 140 (G140S) on HIV IN and its effects on IN inhibitor resistance are described. 2003 Virology Abstract HIV G140S;G140S 77;33 82;75 IN;IN 91;113 93;115 12620807 Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. IN(G140S) was resistant to both L-CA and L-731,988, a diketoacid. 2003 Virology Abstract HIV G140S 3 8 IN;Capsid 0;34 2;36 12620807 Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. The G140S mutation attenuates IN activity and confers resistance to IN inhibitors, suggesting that diketoacids and L-CA interact with a similar binding site on HIV IN. 2003 Virology Abstract HIV G140S 4 9 IN;IN;IN;Capsid 30;68;164;117 32;70;166;119 12620807 Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. The mutant protein (IN(G140S)) was attenuated approximately four-fold for catalysis under equilibrium conditions compared to wild-type IN (IN(WT)) and attenuated five-fold in steady-state kinetic analysis of disintegration. 2003 Virology Abstract HIV G140S 23 28 IN;IN;IN 20;135;139 22;137;141 12629637 Introduction of HIV type 1 non-B subtypes into Eastern Andalusia through immigration. Resistance mutation K70R was detected in one of the six immigrants with non-B subtype and M41L in another. 2003 Journal of medical virology Abstract HIV K70R;M41L 20;90 24;94 12643279 Prevalence of drug-resistance-associated mutations in antiretroviral drug-naive Zambians infected with subtype C HIV-1. The atypical residues M41N (3.6%) and D67A (3.6%) were detected in the RT gene. 2003 AIDS research and human retroviruses Abstract HIV D67A;M41N 38;22 42;26 RT 71 73 12643279 Prevalence of drug-resistance-associated mutations in antiretroviral drug-naive Zambians infected with subtype C HIV-1. The generated sequences revealed only secondary associated, but no primary, drug-resistance mutations The most frequent secondary mutations in the protease and RT genes were, respectively, I93L(91.7%), L89M (79.2%), M3611V (79%, 4.2%), and R211K (70.8%), S48T (62.5%). 2003 AIDS research and human retroviruses Abstract HIV I93L;L89M;M3611V;R211K;S48T 189;202;216;240;255 193;206;222;245;259 PR;RT 147;160 155;162 12651859 Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses. HIV-1 with the reverse transcriptase mutations K65R, L74V, and/or Q151M were less sensitive to DXG, whereas the mutation K103N re-sensitized the virus to the inhibitory effect of DXG. 2003 The Journal of biological chemistry Abstract HIV K103N;K65R;L74V;Q151M 121;47;53;66 126;51;57;71 RT 15 36 12651859 Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses. In vitro, HIV-1 mutants resistant to 3'-azido-3'-deoxythymidine (M41L/D67N/K70R/T215Y/K219Q) and (-)beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) (M184V) remain sensitive to DXG. 2003 The Journal of biological chemistry Abstract HIV M41L;D67N;K219Q;K70R;T215Y;M184V 65;70;86;75;80;144 69;74;91;79;85;149 12660525 Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors. Most NRTI mutations group into one of three clusters, although several (e.g., M184V) occur in multiple mutational contexts. 2003 AIDS (London, England) Abstract HIV M184V 78 83 NRTI 5 9 12670953 Reversion of the lethal phenotype of an HIV-1 integrase mutant virus by overexpression of the same integrase mutant protein. Altogether, our data indicate that L172A/K173A mutations of IN induce a subtle defect in the function of IN, which nevertheless dramatically impairs viral replication. 2003 The Journal of biological chemistry Abstract HIV K173A;L172A 41;35 46;40 IN;IN 60;105 62;107 12670953 Reversion of the lethal phenotype of an HIV-1 integrase mutant virus by overexpression of the same integrase mutant protein. In vitro assays using long term repeat mimics, however, demonstrate that the L172A/K173A IN mutant was catalytically active. 2003 The Journal of biological chemistry Abstract HIV K173A;L172A 83;77 88;82 IN 89 91 12670953 Reversion of the lethal phenotype of an HIV-1 integrase mutant virus by overexpression of the same integrase mutant protein. Moreover, trans-complementation experiments show that the viral propagation of L172A/K173A viruses could be rescued by the overexpression of Vpr.L172A/K173A IN fusion protein in a dose-dependent manner and that this rescue is independent of UNG2 packaging. 2003 The Journal of biological chemistry Abstract HIV K173A;K173A;L172A;L172A 85;151;145;79 90;156;150;84 Vpr;IN 141;157 144;159 12670953 Reversion of the lethal phenotype of an HIV-1 integrase mutant virus by overexpression of the same integrase mutant protein. We show that the L172A/K173A IN mutant virus was deficient for UNG2 packaging and was defective for replication because of a blockage at the stage of proviral DNA integration in host cell DNA. 2003 The Journal of biological chemistry Abstract HIV K173A;L172A 23;17 28;22 IN 29 31 12699382 An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study. An X-ray structure (resolution 2.2 A) of mutant HIV-1 protease (A71V, V82T, I84V) complexed with a newly developed peptidomimetic inhibitor with an ethylenamine isostere Boc-Phe-Psi[CH(2)CH(2)NH]-Phe-Glu-Phe-NH(2), denoted as OE, is described and compared with the complex of wild-type HIV-1 protease with the same inhibitor (resolution 2.5 A). 2003 Journal of medicinal chemistry Abstract HIV A71V;I84V;V82T 64;76;70 68;80;74 PR;PR 54;292 62;300 12700444 Improving lopinavir genotype algorithm through phenotype correlations: novel mutation patterns and amprenavir cross-resistance. Several previously defined LPV mutations were found to have a stronger than average effect (e.g., M46I/L, I54V/T, V82A/F), and new variants at known positions (e.g., I54A/M/S, V82S) were identified. 2003 AIDS (London, England) Abstract HIV I54A;I54M;I54S;I54T;I54V;M46I;M46L;V82A;V82F;V82S 166;166;166;106;106;98;98;114;114;176 174;174;174;112;112;104;104;120;120;180 12700457 Brazilian Network for HIV Drug Resistance Surveillance (HIV-BResNet): a survey of chronically infected individuals. Accessory mutations were found in the PR gene at the following positions: L63P/V/T/A/I [153/345 (44.3%)], M36I/L [149/345 (43.2%)], L10I/F/V [82/345 (23.8%)], V77I [60/345 (17.4%)], A71V/T [11/345 (3.2%)], K20M/R [10/345 (2.9%)], and V82I [4/345 (1.2%)]. 2003 AIDS (London, England) Abstract HIV A71T;A71V;K20M;K20R;L10F;L10I;L10V;L63A;L63I;L63P;L63T;L63V;M36I;M36L;V77I;V82I 182;182;206;206;132;132;132;74;74;74;74;74;106;106;159;234 188;188;212;212;140;140;140;86;86;86;86;86;112;112;163;238 PR 38 40 12700457 Brazilian Network for HIV Drug Resistance Surveillance (HIV-BResNet): a survey of chronically infected individuals. Mutations known to be associated with reduced sensitivity to NRTI or NNRTI (V118I, E44D, K219R, T69A, and V75L) were found in a low prevalence (0.6-2.4%). 2003 AIDS (London, England) Abstract HIV E44D;K219R;T69A;V118I;V75L 83;89;96;76;106 87;94;100;81;110 NNRTI;NRTI 69;61 74;65 12700461 Primary resistance mutations to fusion inhibitors and polymorphisms in gp41 sequences of HIV-1 non-B subtypes and recombinants. L91H to RPR103611 was detected in one DGpol/Denv/Dgp41 recombinant; L9F and K144R, rarely reported previously, were frequent in the B region of CRF14_BG recombinants. 2003 AIDS (London, England) Abstract HIV K144R;L9F;L91H 76;68;0 81;71;4 12700461 Primary resistance mutations to fusion inhibitors and polymorphisms in gp41 sequences of HIV-1 non-B subtypes and recombinants. V194I and V318A, not described in the G subtype, were detected in the G region of BG recombinants and in G subtype viruses that also show the rare mutations T115L, M118V and K90R. 2003 AIDS (London, England) Abstract HIV K90R;M118V;T115L;V318A;V194I 174;164;157;10;0 178;169;162;15;5 12704265 [HIV genotypic mutation selectively induced by the protease inhibitor nelfinavir at codon 30. Case series and consequences for antiretroviral management]. In a survey of 247 HIV-infected patients which received at least six months of combined antiretroviral therapy including the protease inhibitor nelfinavir during the last two years (2000-2001), the specific primary genotypic mutation D30N (with or without the minor mutation N88D), was detected in only four of the 149 (2.7%) subjects who received genotypization after virological failure. 2002 Le infezioni in medicina Abstract HIV D30N;N88D 234;275 238;279 PR 125 133 HIV infections 19 31 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. Among patients who interrupted 3TC, overall prevalence of M184V/I was 23.1%: proportion of patients carrying the M184V/I dropped from 83.3% among those who interrupted 3TC from < or = 3 months, to 56.3, 20, 10.5 and 0% for those interrupting 3TC from 6, 12, 24 and > or = 24 months, respectively. 2003 Antiviral therapy Abstract HIV M184I;M184I;M184V;M184V 58;113;58;113 65;120;65;120 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. At logistic regression analysis, the rate of increase of M184V/I in 3TC-failing patients was statistically significant (OR: 1.066 per month of current 3TC therapy, 95% CI: 1.020-1.114, P<0.01), suggesting a 6.6% monthly increase of probability of M184V/I. 2003 Antiviral therapy Abstract HIV M184I;M184I;M184V;M184V 57;247;57;247 64;254;64;254 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. At logistic regression, the rate of disappearance of M184V/I was also statistically significant (OR: 0.883 per month, 95% CI: 0.804-0.970, P=0.01), indicating a 11.7% monthly decrease of probability of M184V/I after 3TC interruption. 2003 Antiviral therapy Abstract HIV M184I;M184I;M184V;M184V 53;202;53;202 60;209;60;209 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. CONCLUSIONS: Dynamics of appearance/disappearance of M184V/I mutation is rapid after 3TC failure/interruption, suggesting ease of development of such a mutation, but also suggesting a remarkable growth disadvantage for HIV. 2003 Antiviral therapy Abstract HIV M184I;M184V 53;53 60;60 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. From the clinical perspective, recycling of drugs whose antiviral activity is affected by M184V mutation can be successful after appropriate drug wash-out, also in heavily pretreated patients. 2003 Antiviral therapy Abstract HIV M184V 90 95 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. OBJECTIVE: M184V/I mutation is associated with high-level phenotypic resistance to lamivudine (3TC). 2003 Antiviral therapy Abstract HIV M184I;M184V 11;11 18;18 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. Prevalence of M184V/I was associated to longer history of 3TC (from 47.1% in patients treated with 3TC for <6 months, to 84.0% among those treated for 7-12 months; 100.0% of patients with >42 months of current 3TC carried M184V. 2003 Antiviral therapy Abstract HIV M184I;M184V;M184V 14;14;222 21;21;227 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. RESULTS: Among patients currently undergoing 3TC-containing HAART, the prevalence of M184V/I was 82.5% (78.3/4.2%, respectively) and significantly associated to current 3TC use at GRT. 2003 Antiviral therapy Abstract HIV M184I;M184V 85;85 92;92 12713064 Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation. The aim of the present analysis was to correlate the time of appearance/disappearance of M184V/I with duration of 3TC treatment. 2003 Antiviral therapy Abstract HIV M184I;M184V 89;89 96;96 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. Four of the six viruses that had 215C/D mutations at baseline acquired the 215Y mutation alone or in association with K65R. 2003 Journal of virology Abstract HIV K65R 118 122 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. K65R was selected in seven viruses and was associated with a high level of enzymatic resistance to d4T-triphosphate (median, 16-fold; range, 5- to 48-fold). 2003 Journal of virology Abstract HIV K65R 0 4 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. Mutants having K65R and T215Y replicated less efficiently than viruses that had T215Y only, suggesting that selection of T215Y in patients treated with d4T may be favored. 2003 Journal of virology Abstract HIV K65R;T215Y;T215Y;T215Y 15;24;80;121 19;29;85;126 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. Our results demonstrate that K65R plays a role in d4T resistance and indicate that resistance pathways for d4T and AZT may not be identical. 2003 Journal of virology Abstract HIV K65R 29 33 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. Passaged viruses were derived from treatment-naive persons or HIV-1(HXB2) and had wild-type reverse transcriptase (RT) or T215C/D mutations. 2003 Journal of virology Abstract HIV T215C;T215D 122;122 129;129 RT;RT 92;115 113;117 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. Phenotypic assays based on recombinant single-cycle replication or a whole-virus multiple replication cycle were unable to detect d4T resistance in d4T-selected mutants with K65R but detected cross-resistance to other nucleoside RT inhibitors. 2003 Journal of virology Abstract HIV K65R 174 178 RT 229 231 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. The role of K65R in d4T resistance was confirmed in site-directed mutants generated in three different RT backgrounds. 2003 Journal of virology Abstract HIV K65R 12 16 RT 103 105 12719561 A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. Through the analysis of genotypic changes in nine recombinant viruses cultured with d4T, we identified a new pathway for d4T resistance mediated by K65R, a mutation not selected by AZT. 2003 Journal of virology Abstract HIV K65R 148 152 12719577 Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template. Molecular dynamics modeling suggested that N265D leads to a loss of template strand-specific hydrogen bonding, indicating that this is a key determinant of the differential template affinity. 2003 Journal of virology Abstract HIV N265D 43 48 12719577 Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template. The mutations are N255D and N265D, both adjoining the minor groove-binding track, in the thumb region. 2003 Journal of virology Abstract HIV N255D;N265D 18;28 23;33 12719577 Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template. The N255D substitution caused local changes in conformation and a consequent loss of interaction with the primer, leading to a loss of processive synthesis with both templates. 2003 Journal of virology Abstract HIV N255D 4 9 12719577 Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template. The N265D substitution led to a loss of processive polymerization on DNA but not on RNA, whereas N255D drastically reduced processive synthesis on both templates. 2003 Journal of virology Abstract HIV N255D;N265D 97;4 102;9 12719577 Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template. This differential template usage was accompanied by a rapid dissociation of the N265D variant on DNA but not RNA templates, whereas the N255D variant rapidly dissociated from both templates. 2003 Journal of virology Abstract HIV N255D;N265D 136;80 141;85 12731757 Selection and characterization of HIV-1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC). Clinical isolates of HIV-1 resistant to lamivudine and containing the M184V substitution also displayed low-level resistance to both (-) and (+) dOTC when grown in CBMC. 1999 Antiviral therapy Abstract HIV M184V 70 75 12731757 Selection and characterization of HIV-1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC). Cloning and sequencing of the complete reverse transcriptase (RT) coding region of these variants identified the M1841 mutation and further selection with virus containing the M1841 substitution led to the appearance of an M184V mutation. 1999 Antiviral therapy Abstract HIV M184V 223 228 RT;RT 39;62 60;64 12731757 Selection and characterization of HIV-1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC). Finally, cell-free RT assays were performed in the presence of either (-) dOTC triphosphate, (+) dOTC triphosphate, or the triphosphate of a racemic mixture of (+) and (-) dOTC with wild-type and mutated M184V-containing recombinant RT. 1999 Antiviral therapy Abstract HIV M184V 204 209 RT;RT 19;233 21;235 12731757 Selection and characterization of HIV-1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC). Site-directed mutagenesis experiments in which the M1841 and M184V mutations were introduced into HXB2D confirmed the importance of these mutations when viruses were grown in MT4 cells. 1999 Antiviral therapy Abstract HIV M184V 61 66 12734932 [Drug resistance of HIV-infected patients after the failure of highly active antiretroviral treatment]. Mutations such as V179I in RT and K20T, K20I etc in protease may be related to drug resistance. 2003 Zhejiang da xue xue bao. Yi xue ban Abstract HIV K20I;K20T;V179I 40;34;18 44;38;23 PR;RT 52;27 60;29 12734932 [Drug resistance of HIV-infected patients after the failure of highly active antiretroviral treatment]. Some mutations existed in some patients, such as V179I in RT and K20T, K20I in protease, which hadn't been reported in the resistant database of Stanford University yet. 2003 Zhejiang da xue xue bao. Yi xue ban Abstract HIV K20I;K20T;V179I 71;65;49 75;69;54 PR;RT 79;58 87;60 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. Baseline Y181C was associated with the development of mutations at position 190, but not L100I or K103N. 2003 Antiviral therapy Abstract HIV K103N;L100I;Y181C 98;89;9 103;94;14 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. In this patient population, abacavir with efavirenz preferentially selected for L74V but not for thymidine analogue mutations. 2003 Antiviral therapy Abstract HIV L74V 80 84 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. L100I and G190A/S/E/T mutations were rarely detected in the same viral population and baseline Y181C favoured the G190 mutations (OR=8.9, P<0.001), rather than the L100I. 2003 Antiviral therapy Abstract HIV G190A;G190E;G190S;G190T;L100I;Y181C;L100I 10;10;10;10;164;95;0 21;21;21;21;169;100;5 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. M184V was common at baseline (55%) and maintained in 22/27 (81%) isolates (five of these 22 added lamivudine or didanosine, or both). 2003 Antiviral therapy Abstract HIV M184V 0 5 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. M184V was rarely selected and was maintained in only 77% of patients who did not add lamivudine or didanosine. 2003 Antiviral therapy Abstract HIV M184V 0 5 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. Mutations D30N, G48V, N88D/S, L90M and 154V were de-selected, and mutations I50V, I or V to 54M/L, I84V, M46I/L, L33F, I47V as well mutations at position 10 were observed in 20/49 (41%) isolates. 2003 Antiviral therapy Abstract HIV D30N;G48V;I47V;I50V;I84V;L33F;L90M;M46I;M46L;N88D;N88S 10;16;119;76;99;113;30;105;105;22;22 14;20;123;80;103;117;34;111;111;28;28 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. NNRTI mutations selected on therapy were K103N (51%), substitutions at position 190 (17/49, 35%): G to A (n=11) / S (n=4) / E (n=1) and T (n=1); L100I (37%) and V1081 (20%) mutations. 2003 Antiviral therapy Abstract HIV K103N;L100I 41;145 46;150 NNRTI 0 5 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. P225H was not observed in this study. 2003 Antiviral therapy Abstract HIV P225H 0 5 12741623 HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. The NRTI mutations selected were in accordance with abacavir known resistance profile, no new TAMs were observed, new L74V or I mutations developed in 39 and 16% of isolates, respectively, however, new M184V mutations were only detected in isolates from two patients, one of whom had added lamivudine + didanosine. 2003 Antiviral therapy Abstract HIV L74V;M184V 118;202 122;207 NRTI 4 8 12741624 Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. After a run-in phase consisting in a new treatment regimen excluding either lamivudine (3TC) or abacavir (ABC) so as to clear the previously documented M184V mutation, 18 patients with an HIV RNA plasma level greater than 10000 copies/ml were randomized to receive an antiretroviral drug regimen (at least three drugs) including either ABC or the association of ABC+3TC. 2003 Antiviral therapy Abstract HIV M184V 152 157 12741624 Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. The M184V mutation reappeared in 1/9 patients in the ABC group and in 8/9 patients in the ABC+3TC group (P<0.003, 95% CI: 0.5-1). 2003 Antiviral therapy Abstract HIV M184V 4 9 12741624 Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. The possibility of a successful use of ABC in salvage regimens opens alternative therapeutic options for heavily pretreated patients with previously documented M184V mutation. 2003 Antiviral therapy Abstract HIV M184V 160 165 12741624 Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. The primary end-point of the study was the reselection of M184V mutation. 2003 Antiviral therapy Abstract HIV M184V 58 63 12741624 Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. We evaluated in an open-label, randomized, controlled, pilot trial if the re-emergence of previously selected resistant strains, harbouring M184V mutation, could be modulated by the use of different drug associations as components of the new antiretroviral regimens. 2003 Antiviral therapy Abstract HIV M184V 140 145 12741630 K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. All five patients with wild-type virus developed K65R and four of these patients also acquired the S68G mutation. 2003 Antiviral therapy Abstract HIV K65R;S68G 49;99 53;103 12741630 K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. Failure of a triple NRTI regimen is possible and frequent with only the K65R mutation. 2003 Antiviral therapy Abstract HIV K65R 72 76 NRTI 20 24 12741630 K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. In two patients with baseline resistance mutations, further accumulation of NEMs and V75T or L74V was observed. 2003 Antiviral therapy Abstract HIV L74V;V75T 93;85 97;89 12741630 K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. One patient developed Q151M. 2003 Antiviral therapy Abstract HIV Q151M 22 27 12741630 K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. The unexpected high incidence of S68G suggests a functional role of this mutation in viruses harbouring K65R. 2003 Antiviral therapy Abstract HIV K65R;S68G 104;33 108;37 12741630 K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. Under adequate selection pressure K65R can easily emerge in vivo and may compromise several future treatment options including newer NRTIs. 2003 Antiviral therapy Abstract HIV K65R 34 38 NRTI 133 138 12742017 Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs. Alteration of Glu895 to Ala slightly increased discrimination against dideoxynucleotides and D4T-TP. 2003 Journal of molecular biology Abstract HIV E895A 14 27 12742017 Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs. Mutation of Tyr951 to Phe renders the enzyme resistant to dideoxynucleotides and D4T-TP without compromising the activity of the polymerase. 2003 Journal of molecular biology Abstract HIV Y951F 12 25 Pol 129 139 12743270 Relationship between 3'-azido-3'-deoxythymidine resistance and primer unblocking activity in foscarnet-resistant mutants of human immunodeficiency virus type 1 reverse transcriptase. We have compared the primer-unblocking activity for HIV-1 RT containing various foscarnet resistance mutations (K65R, W88G, W88S, E89K, S117T, Q161L, M164I, and the double mutant Q161L/H208Y) alone or in combination with AZT resistance mutations. 2003 Journal of virology Abstract HIV E89K;H208Y;K65R;M164I;Q161L;Q161L;S117T;W88G;W88S 130;185;112;150;143;179;136;118;124 134;190;116;155;148;184;141;122;128 RT 58 60 12750404 Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. In addition, T cell infections using vesicular stomatitis virus G (VSV-G) pseudotyped HIV-1 Vpr R77Q result in less (P = 0.01) T cell death than infections using wild-type Vpr, despite similar levels of viral replication. 2003 The Journal of clinical investigation Abstract HIV R77Q 96 100 Vpr;Vpr 92;172 95;175 12750404 Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. We demonstrate a higher frequency of R77Q Vpr mutations in patients with LTNP than in patients with progressive disease. 2003 The Journal of clinical investigation Abstract HIV R77Q 37 41 Vpr 42 45 12750404 Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. Wild-type Vpr-associated events, including procaspase-8 and -3 cleavage, loss of mitochondrial transmembrane potential (deltapsi(m)), and DNA fragmentation factor activation are attenuated by R77Q Vpr. 2003 The Journal of clinical investigation Abstract HIV R77Q 192 196 Vpr;Vpr 10;197 13;200 12767471 Elucidation of HIV-1 protease resistance by characterization of interaction kinetics between inhibitors and enzyme variants. The kinetics of the interaction between drug-resistant variants of HIV-1 protease (G48V, V82A, L90M, I84V/L90M, and G48V/V82A/I84V/L90M) and clinically used inhibitors (amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir) were determined using biosensor technology. 2003 Antiviral research Abstract HIV G48V;I84V;L90M;V82A;G48V;I84V;L90M;L90M;V82A 116;126;131;121;83;101;106;95;89 120;130;135;125;87;105;110;99;93 PR 73 81 12767994 Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene. In contrast, the mutant PR82A(76-84) epitope is generally not recognized by wild-type-specific CTL, or when recognized it is of low to moderate avidity, suggesting that the protease inhibitor-selected V82A mutation acts both as a CTL and protease inhibitor escape mutant. 2003 Journal of virology Abstract HIV V82A 201 205 PR;PR;PR 173;238;24 181;246;26 12767994 Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene. This epitope, which is HLA-A2 restricted, includes two amino acids that commonly mutate (V82A and I84V) in the face of protease inhibitor therapy. 2003 Journal of virology Abstract HIV I84V;V82A 98;89 102;94 PR 119 127 12781181 The role of 2',3'-unsaturation on the antiviral activity of anti-HIV nucleosides against 3TC-resistant mutant (M184V). In 3TC-resistant mutant (M184V) RT, 2'-fluoro-2',3'-unsaturated nucleosides with a bulky 4'-substituent experience significant steric hindrance with the side chain of Val184. 2003 Bioorganic & medicinal chemistry letters Abstract HIV M184V 25 30 RT 32 34 12785806 Validation of a model for the complex of HIV-1 reverse transcriptase with nonnucleoside inhibitor TMC125. The good quantitative agreement between the computed and experimental anti-HIV activities for TMC125, nevirapine, and efavirenz with wild-type RT and four common mutants (L100I, K103N, Y181C, and Y188L) confirms the correctness of the predicted structure and provides insights into the improved potency of this novel NNRTI. 2003 Journal of the American Chemical Society Abstract HIV K103N;L100I;Y181C;Y188L 178;171;185;196 183;176;190;201 NNRTI;RT 317;143 322;145 12790516 HIV-1 resistance profile of the novel nucleoside reverse transcriptase inhibitor beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (Reverset). D-d4FC is highly effective at inhibiting subsets of lamivudine- and zidovudine-resistant variants but, like other NRTIs, seems less potent against multi-NRTI-resistant viruses, particularly those carrying the Q151M complex of mutations. 2003 Antiviral chemistry & chemotherapy Abstract HIV Q151M 209 214 NRTI;NRTI 114;153 119;157 12790516 HIV-1 resistance profile of the novel nucleoside reverse transcriptase inhibitor beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (Reverset). Finally, in vitro selections for HIV-1 mutants capable of replicating in the presence of D-d4FC yielded a mutant carrying the RT K65R mutation. 2003 Antiviral chemistry & chemotherapy Abstract HIV K65R 129 133 RT 126 128 1279207 Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: effects on nucleoside analog resistance. A Glu-89-->Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). 1992 Journal of virology Abstract HIV E89G 2 14 RT;RT 69;92 90;94 1279207 Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: effects on nucleoside analog resistance. Furthermore, the introduction of Glu-89-->Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA. 1992 Journal of virology Abstract HIV E89G 33 45 RT 66 68 12792350 Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses. These 96-week results were analogous to the 48-week results, in which 33% (n = 63) and 2.1% (n = 4) of patients developed thymidine analog-associated mutations or the K65R mutation, respectively. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 167 171 12792350 Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses. Through 96 weeks of tenofovir DF therapy, 48 weeks of which included suboptimal doses of tenofovir DF, there was infrequent development of RT mutations associated with tenofovir DF therapy (K65R mutation, 3%), consistent with the durability of the observed HIV-1 RNA responses. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 190 195 RT 139 141 12792350 Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses. Two patients (1.5%) developed the K65R RT mutation (selected by tenofovir in vitro) but maintained HIV-1 suppression (-0.39 log(10)). 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 34 38 RT 39 41 12797395 Prevalence and virologic consequences of HIV-1 genotype mutations detected in a cohort of 161 Italian patients receiving a nelfinavir-based highly active antiretroviral therapy. Among the 80 failed patients, the M184V mutation was detected in 52 (65%), while only 7 patients showed simultaneously the M184V, T215Y and K103N substitutions. 2003 Journal of chemotherapy (Florence, Italy) Abstract HIV K103N;M184V;M184V;T215Y 140;34;123;130 145;39;128;135 12797395 Prevalence and virologic consequences of HIV-1 genotype mutations detected in a cohort of 161 Italian patients receiving a nelfinavir-based highly active antiretroviral therapy. In our HIV-infected population receiving a nelfinavir-based HAART, the D30N mutation has shown a low absolute frequency, while the detection of M184V substitution and the simultaneous occurrence of M184V, T215Y and K103N mutations were related to a more favorable virological response. 2003 Journal of chemotherapy (Florence, Italy) Abstract HIV D30N;K103N;M184V;M184V;T215Y 71;215;144;198;205 75;220;149;203;210 HIV infections 7 19 12797395 Prevalence and virologic consequences of HIV-1 genotype mutations detected in a cohort of 161 Italian patients receiving a nelfinavir-based highly active antiretroviral therapy. On the whole, only 11 patients (7%) developed the D30N substitution, whose 6 was in association with the N88D mutation. 2003 Journal of chemotherapy (Florence, Italy) Abstract HIV D30N;N88D 50;105 54;109 12816080 The molecular epidemiology and drug resistance determination of HIV type 1 subtype B infection in Barbados. Only two RT antiretroviral resistance mutations (M41L and T215Y) were observed, both from a single patient. 2003 AIDS research and human retroviruses Abstract HIV M41L;T215Y 49;58 54;63 RT 9 11 12816080 The molecular epidemiology and drug resistance determination of HIV type 1 subtype B infection in Barbados. The frequency of subtype B HIV-1 variants with similar env V3 features, including the tetrameric tips, GPGR and GPGK, the threonine deletion at position 23, and the substitution of threonine to arginine at position 22, was comparable in heterosexual, bisexual, and homosexual patients. 2003 AIDS research and human retroviruses Abstract HIV T22R 181 217 Env 55 58 12816080 The molecular epidemiology and drug resistance determination of HIV type 1 subtype B infection in Barbados. While the occurrence of 361, 63P, and 71T mutations in Barbadian strains was similar to the global prevalence for subtype B variants, the frequency (64%) of the V77I mutation was more than three times that seen worldwide. 2003 AIDS research and human retroviruses Abstract HIV V77I 161 165 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. Both mechanisms show a certain degree of incompatibility; however, previous clinical data revealed that mutations E44D and V118I, when present in a background of classical AZT mutations (M41L, D67N, L210W, and T215Y), confer dual resistance to AZT and 3TC. 2003 The Journal of biological chemistry Abstract HIV D67N;E44D;L210W;M41L;T215Y;V118I 193;114;199;187;210;123 197;118;204;191;215;128 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. Our findings are consistent with an increasing number of clinical studies suggesting that the V118I cluster constitutes a novel pathway for HIV resistance to multiple nucleotide analogue RT inhibitors. 2003 The Journal of biological chemistry Abstract HIV V118I 94 99 RT 187 189 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. The additional presence of mutations M41L, D67N, L210W, and T215Y can partially neutralize this deficit, which helps to explain the concurrent presence of these changes in resistant isolates. 2003 The Journal of biological chemistry Abstract HIV D67N;L210W;M41L;T215Y 43;49;37;60 47;54;41;65 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. The M184V mutation in the reverse transcriptase (RT) of the human immunodeficiency virus, type 1 (HIV-1) diminishes the incorporation of 3TC-monophosphate (3TC-MP), whereas AZT resistance-conferring mutations were shown to facilitate the phosphorolytic excision of incorporated AZT-MP in the presence of ATP. 2003 The Journal of biological chemistry Abstract HIV M184V 4 9 RT;RT 26;49 47;51 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. The V118I mutant is also associated with diminished rates of ATP-dependent primer unblocking. 2003 The Journal of biological chemistry Abstract HIV V118I 4 9 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. These biochemical data make clear that mutations E44D and V118I play distinct mechanistic roles in dual resistance to AZT and 3TC. 2003 The Journal of biological chemistry Abstract HIV E44D;V118I 49;58 53;63 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. Unexpectedly, V118I-containing enzymes show dramatic reductions in rates of incorporation of AZT-MP and 3TC-MP. 2003 The Journal of biological chemistry Abstract HIV V118I 14 19 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. We found that enzymes containing E44D in a background of these latter mutations increase the efficiency of excision of 3TC-MP. 2003 The Journal of biological chemistry Abstract HIV E44D 33 37 12819190 Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. We have purified RT enzymes that contain E44D and V118I either alone or in a background of different combinations of AZT mutations to study the underlying biochemical mechanisms. 2003 The Journal of biological chemistry Abstract HIV E44D;V118I 41;50 45;55 RT 17 19 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. CONCLUSION: HIV-1(Q151M) probably develops through a poorly replicating HIV-1(Q151L); however, it is also possible that it occurs through two concurrent base changes. 2003 AIDS (London, England) Abstract HIV Q151L;Q151M 78;18 83;23 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. DESIGN AND METHODS: Propagation assays and competitive HIV-1 replication assays were used to evaluate the fitness of various infectious clones, including two putative intermediates (HIV-1(Q151K(AAG)) and HIV-(1Q151L(CTG))) for HIV-1(Q151M(ATG)), in terms of sensitivity to zidovudine and didanosine. 2003 AIDS (London, England) Abstract HIV Q151K;Q151M 188;233 193;238 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. Enzymatic assays corroborated that HIV-1(Q151L) is more replication-competent than HIV-1(WT) and HIV-1(Q151K) in the presence of drugs. 2003 AIDS (London, England) Abstract HIV Q151K;Q151L 103;41 108;46 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. HIV-1(Q151M) was less susceptible to drugs, while HIV-1(Q151L/M230I) was as sensitive as HIV-1(WT). 2003 AIDS (London, England) Abstract HIV Q151L;M230I;Q151M 56;62;6 61;67;11 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. OBJECTIVE: To investigate the mechanism by which the Q151M mutation in reverse transcriptase (RT) that confers multi-dideoxynucleoside resistance on HIV-1 and that requires a two base change (CAG-->ATG) develops, and to understand the reason for the relatively lengthy period of time required for its emergence under therapy with multiple nucleoside RT inhibitors (NRTI). 2003 AIDS (London, England) Abstract HIV Q151M 53 58 RT;NRTI;RT;RT 71;365;94;350 92;369;96;352 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. RESULTS: HIV-1(Q151L) replicated relatively poorly while HIV-1(Q151K) failed to replicate. 2003 AIDS (London, England) Abstract HIV Q151K;Q151L 63;15 68;20 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. The present data should explain the mechanism by which HIV-1(Q151M) emerges after long-term chemotherapy with NRTI. 2003 AIDS (London, England) Abstract HIV Q151M 61 66 NRTI 110 114 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. The relative order of replicative fitness without drugs was: HIV-1(Q151M) > HIV-1(WT) > HIV-1(Q151L/M230I) > HIV-1(M230I) >> HIV-1(Q151L) >>> HIV-1(Q151K), HIV-1(Q151K/M230I). 2003 AIDS (London, England) Abstract HIV Q151K;Q151L;M230I;M230I;M230I;Q151K;Q151L;Q151M 162;94;100;168;115;148;131;67 167;99;105;173;120;153;136;72 12819513 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. When HIV-1(Q151L) was propagated further, it took three pathways in continuing to replicate: (i) HIV-1(Q151L) changed to HIV-1(Q151M) in eight of 16 experiments; (ii) HIV-1(Q151L) reverted to wild-type HIV-1 (HIV-1(WT)) in four of 16 experiments; and (iii) HIV-1(Q151L) acquired an additional mutation M230I in four of 16 experiments improving HIV-1 fitness. 2003 AIDS (London, England) Abstract HIV M230I;Q151L;Q151L;Q151L;Q151L;Q151M 302;11;103;173;263;127 307;16;108;178;268;132 12821504 The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase delays the development of resistance to amprenavir and efavirenz in subtype B and C clinical isolates. Genotypic analysis revealed differences in EFV resistance-conferring mutations in subtype B (K103N) versus subtype C (V106 M), and the appearance of both was significantly delayed in the M184V-containing variants compared with the wild type (WT). 2003 Antimicrobial agents and chemotherapy Abstract HIV K103N;M184V;V106M 93;187;118 98;192;124 12821504 The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase delays the development of resistance to amprenavir and efavirenz in subtype B and C clinical isolates. Similarly, there was a marked delay in the emergence of mutations associated with APV resistance (I54 M/L/V) in subtype B viruses harboring M184V compared with paired WT viral isolates. 2003 Antimicrobial agents and chemotherapy Abstract HIV I54L;I54M;I54V;M184V 98;98;98;140 107;107;107;145 12821504 The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase delays the development of resistance to amprenavir and efavirenz in subtype B and C clinical isolates. The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), encoding high-level resistance to lamivudine (3TC), results in decreased HIV-1 replicative capacity, diminished RT processivity, and increased RT fidelity in biochemical assays. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 4 9 RT;RT;RT;RT 70;93;210;241 91;95;212;243 12821504 The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase delays the development of resistance to amprenavir and efavirenz in subtype B and C clinical isolates. We assessed the effect of M184V on the development of resistance to the nonnucleoside RT inhibitors efavirenz (EFV) and nevirapine, and to the protease inhibitor amprenavir (APV) in tissue culture. 2003 Antimicrobial agents and chemotherapy Abstract HIV M184V 26 31 PR;RT 143;86 151;88 12824484 A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. NMR studies of the binding of a substrate to an inactive HIV-1 protease construct, containing an active site mutation PR(D25N), are reported. 2003 Protein science Abstract HIV D25N 121 125 PR;PR 63;118 71;120 12824484 A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Substrate titration measurements monitored by HSQC spectra and a (15)N-edited NOESY experiment show that the chromogenic substrate analog of the capsid/p2 cleavage site binds to PR(D25N) with an equilibrium dissociation constant, K(D), of 0.27 +/- 0.05 mM, and upper limits of the association and dissociation rate constants, 2 x 10(4) M(-1)s(-1) and 10 s(-1), respectively, at 20 degrees C, pH 5.8. 2003 Protein science Abstract HIV D25N 181 185 Capsid;PR 145;178 151;180 12824799 Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudine. A previously unnoticed role of Y181I/C RT changes selected by nevirapine or other NNRTI in determining stavudine resistance is documented. 2003 AIDS (London, England) Abstract HIV Y181C;Y181I 31;31 38;38 NNRTI;RT 82;39 87;41 12824799 Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudine. However, recombinant Y181C HIV-1 showed reduced stavudine susceptibility with respect to both recombinant wild-type and K103N HIV-1 strains. 2003 AIDS (London, England) Abstract HIV K103N;Y181C 120;21 125;26 12824799 Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudine. In addition, recombinant Y181I RT enzyme showed reduced susceptibility to stavudine with respect to both wild-type and K103N RT. 2003 AIDS (London, England) Abstract HIV K103N;Y181I 119;25 124;30 RT;RT 31;125 33;127 12824799 Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudine. Stavudine administration did not increase the frequency of Y181I/C reverse transcriptase (RT) mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated patients. 2003 AIDS (London, England) Abstract HIV Y181C;Y181I 59;59 66;66 NNRTI;RT;NNRTI;RT 107;67;155;90 143;88;160;92 12824800 Selection of resistance mutations in pregnant women receiving zidovudine and lamivudine to prevent HIV perinatal transmission. The M184V mutation was detected one week after delivery in six out of fifty women (12%) who received the regimen prepartum, intrapartum and postpartum, and was no longer present 3 months later. 2003 AIDS (London, England) Abstract HIV M184V 4 9 1282792 3'-Azido-3'-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors. BI-RG-587 induced a different mutation (V106-->A) in AZT resistance backgrounds. 1992 Antimicrobial agents and chemotherapy Abstract HIV V106A 40 48 1282792 3'-Azido-3'-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors. However, the V106-->A substitution did not cause suppression of preexisting AZT resistance. 1992 Antimicrobial agents and chemotherapy Abstract HIV V106A 13 21 12832217 Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. Clearance from pausing at position +3 during synthesis of viral DNA was identified as a sensitive step in this reaction that could not be efficiently bypassed with the M184V mutant enzyme. 2003 Virology Abstract HIV M184V 168 173 12832217 Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. The M184V mutation in HIV reverse transcriptase (RT) is associated with high-level resistance against the nucleoside inhibitor lamivudine as well as diminished viral replication capacity. 2003 Virology Abstract HIV M184V 4 9 RT;RT 26;49 47;51 12832217 Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. The results showed that the RNA template that contained the A-rich loop deletion was impaired in ability to initiate reverse transcription and that the presence of the M184V substitution in RT amplified this effect. 2003 Virology Abstract HIV M184V 168 173 RT;RT 117;190 138;192 12832217 Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. These templates were then used in cell-free reverse transcription initiation assays and in tRNA primer placement assays performed with either recombinant wild-type RT or recombinant RT containing the M184V substitution. 2003 Virology Abstract HIV M184V 200 205 RT;RT;RT 44;164;182 65;166;184 12832217 Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. We have previously demonstrated that HIV variants containing the M184V mutation were relatively unable to successfully undergo compensatory mutagenesis following deletion of an A-rich loop located upstream of the primer binding site (PBS). 2003 Virology Abstract HIV M184V 65 70 12843034 High prevalence of M184 mutation among patients with viroimmunologic discordant responses to highly active antiretroviral therapy and outcomes after change of therapy guided by genotypic analysis. A relationship between the M184V mutation and a viroimmunologic discordant response to HAART was found. 2003 Journal of clinical microbiology Abstract HIV M184V 27 32 12843034 High prevalence of M184 mutation among patients with viroimmunologic discordant responses to highly active antiretroviral therapy and outcomes after change of therapy guided by genotypic analysis. Based on multivariate analysis, only the M184V mutation remained significantly associated with a viroimmunologic discordant response (odds ratio, 25.48; 95% confidence interval, 1.43 to 453.93). 2003 Journal of clinical microbiology Abstract HIV M184V 41 46 12843034 High prevalence of M184 mutation among patients with viroimmunologic discordant responses to highly active antiretroviral therapy and outcomes after change of therapy guided by genotypic analysis. Based on univariate analysis, a high CD4(+) cell count before antiretroviral treatment, homosexual behavior as a risk factor for HIV infection, reduced drug exposure to nonnucleoside reverse transcriptase inhibitors, low replicative capacity of HIV isolates, and more frequent detection of HIV isolates with a non-B subtype, an R5 biological phenotype, and M184V and T215Y/F mutations were factors associated with a discordant response to HAART. 2003 Journal of clinical microbiology Abstract HIV M184V;T215F;T215Y 357;367;367 362;374;374 NNRTI 169 204 HIV infections 129 142 12843744 Patterns of point mutations associated with antiretroviral drug treatment failure in CRF01_AE (subtype E) infection differ from subtype B infection. The mutations T69N and V75M in reverse transcriptase and L10F, K20I, L33I, and N88S in protease were seen more frequently in patients infected with CRF01_AE than in patients with subtype B. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K20I;L10F;L33I;N88S;T69N;V75M 63;57;69;79;14;23 67;61;73;83;18;27 RT;PR 31;87 52;95 12843744 Patterns of point mutations associated with antiretroviral drug treatment failure in CRF01_AE (subtype E) infection differ from subtype B infection. The mutations, D30N, A71V, and N88D were found exclusively in patients with subtype B. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A71V;D30N;N88D 21;15;31 25;19;35 12852755 l-2',3'-Didehydro-2',3'-dideoxy-3'-fluoronucleosides: synthesis, anti-HIV activity, chemical and enzymatic stability, and mechanism of resistance. The biological results suggest that, in addition to the sugar conformation, the base moiety may also play a role in their interaction with the M184V RT. 2003 Journal of medicinal chemistry Abstract HIV M184V 143 148 RT 149 151 12852755 l-2',3'-Didehydro-2',3'-dideoxy-3'-fluoronucleosides: synthesis, anti-HIV activity, chemical and enzymatic stability, and mechanism of resistance. The cytidine 24 and 5-fluorocytidine 26 analogues, however, showed significantly decreased antiviral activity against the clinically important lamivudine-resistant variants (HIV-1(M184V)). 2003 Journal of medicinal chemistry Abstract HIV M184V 180 185 12852755 l-2',3'-Didehydro-2',3'-dideoxy-3'-fluoronucleosides: synthesis, anti-HIV activity, chemical and enzymatic stability, and mechanism of resistance. This favorable binding mode, however, cannot be maintained when the triphosphate of 3'-fluoro 2',3'-unsaturated nucleoside binds to the active site of M184V RT because the bulky side chain of Val184 occupies the space needed for the nucleotide. 2003 Journal of medicinal chemistry Abstract HIV M184V 151 156 RT 157 159 12853755 Low frequency of the V106M mutation among HIV-1 subtype C-infected pregnant women exposed to nevirapine. Here we describe the presence of V106M in seven out of 141 South African women (5%) 6 weeks after receiving nevirapine. 2003 AIDS (London, England) Abstract HIV V106M 33 38 12853755 Low frequency of the V106M mutation among HIV-1 subtype C-infected pregnant women exposed to nevirapine. V106M is a novel resistance mutation found in subtype C viruses exposed to efavirenz. 2003 AIDS (London, England) Abstract HIV V106M 0 5 12857933 A naturally occurring substitution in human immunodeficiency virus Tat increases expression of the viral genome. Substitution of asparagine for threonine 23 increases Tat transactivation of the HIV-1 promoter and the binding of Tat to the cellular kinase positive transcription elongation factor b (P-TEFb). 2003 Journal of virology Abstract HIV T23N 16 43 Tat;Tat 54;115 57;118 12869832 HIV-1 phenotypic susceptibility to lopinavir (LPV) and genotypic analysis in LPV/r-naive subjects with prior protease inhibitor experience. Current PI therapy (P = 0.002) and indinavir administration (P < 0.001), >5 LPV/r mutations (P < 0.0012), and detection of L10FIRV, K20MR, M46IL, I54VL, A71VT, G73SA, V82AFTS, I84V, and M90L were associated with LPV resistance in univariate analysis. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A71T;A71V;G73A;G73S;I54L;I54V;I84V;K20M;K20R;L10F;L10I;L10R;L10V;M46I;M46L;M90L;V82A;V82F;V82S;V82T 153;153;160;160;146;146;176;132;132;123;123;123;123;139;139;186;167;167;167;167 158;158;165;165;151;151;180;137;137;130;130;130;130;144;144;190;174;174;174;174 PI 8 10 12869832 HIV-1 phenotypic susceptibility to lopinavir (LPV) and genotypic analysis in LPV/r-naive subjects with prior protease inhibitor experience. Factors independently associated with LPV resistance were K20MR (odds ratio [OR], 13.9; 95% confidence interval [CI], 1.3-145.1; P = 0.028), I54VL (OR, 131.7; 95% CI, 10.5-1654.7; P < 0.001), G73SA (OR, 19.2; 95% CI, 1.4-273.7; P = 0.029), and I84V (OR, 177.5; 95% CI, 6.0-5232.5; P = 0.003) mutations and >9 protease mutations (OR, 18.6; 95% CI, 1.6-213.0; P = 0.019). 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G73A;G73S;I54L;I54V;I84V;K20M;K20R 192;192;141;141;244;58;58 197;197;146;146;248;63;63 PR 309 317 12869832 HIV-1 phenotypic susceptibility to lopinavir (LPV) and genotypic analysis in LPV/r-naive subjects with prior protease inhibitor experience. Linear regression analysis demonstrated that each additional LPV mutation and I54VL accounted for much of the fold resistance to LPV (adjusted R2 = 0.70). 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I54L;I54V 78;78 83;83 12871115 Hologram quantitative structure-activity relationships investigations of non-nucleoside reverse transcriptase inhibitors. In particular, the predictive ability of the models derived from dipyridodiazepinone analogues was significantly improved and apparently revealed differentiating structural requirements between WT and Y181C HIV RT inhibition. 2003 Current medicinal chemistry Abstract HIV Y181C 201 206 RT 211 213 12885880 Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. However, the effectiveness of combination therapy with regimens containing these compounds is often not abolished in the presence of these mutations; it has been conjectured that diminished fitness of HIV-1 variants containing L74V and M184V may contribute to sustained antiviral effects in such cases. 2003 Journal of virology Abstract HIV L74V;M184V 227;236 231;241 12885880 Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. The M184V and/or L74V mutation in the reverse transcriptase (RT) gene are frequently found in viral isolates from patients treated with the nucleoside RT inhibitors lamivudine (3TC), abacavir (ABC), and didanosine (ddI). 2003 Journal of virology Abstract HIV L74V;M184V 17;4 21;9 RT;RT;RT 38;61;151 59;63;153 12885880 Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. To understand the biochemical mechanisms responsible for this diminished fitness, we generated a series of recombinant mutated enzymes containing either or both of the L74V and M184V substitutions. 2003 Journal of virology Abstract HIV L74V;M184V 168;177 172;182 12885880 Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. We have determined that viruses containing both L74V and M184V are more impaired in replication capacity than viruses containing either mutation alone. 2003 Journal of virology Abstract HIV L74V;M184V 48;57 52;62 12885880 Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. We observed that the efficiencies of both reactions were diminished with enzymes containing either L74V or M184V and that these effects were significantly amplified with the double mutant. 2003 Journal of virology Abstract HIV L74V;M184V 99;107 103;112 12887265 Tenofovir disoproxil fumarate. Isolates of HIV infrequently developed the K65R mutation during 96 weeks of tenofovir DF therapy. 2003 Drugs Abstract HIV K65R 43 47 12892062 Natural polymorphisms of protease in protease inhibitor-naive HIV-1 infected patients in Korea: a novel L63M in subtype B. A novel polymorphism in subtype B, L63M was detected in two patients. 2003 AIDS research and human retroviruses Abstract HIV L63M 35 39 12892062 Natural polymorphisms of protease in protease inhibitor-naive HIV-1 infected patients in Korea: a novel L63M in subtype B. One patient (2.3%) harbored a primary resistance-conferring mutation, L90M along with L63P and A71V, and all 43 strains showed some secondary associated with drug resistance. 2003 AIDS research and human retroviruses Abstract HIV A71V;L63P;L90M 95;86;70 99;90;74 12895697 HIV-1 resistance to the gp41-dependent fusion inhibitor C-34. The HXB2-derived strain was more than 1000-fold resistant and contained a V38E mutation in the gp41 coding DNA sequence. 2003 Antiviral research Abstract HIV V38E 74 78 gp41 95 99 12895697 HIV-1 resistance to the gp41-dependent fusion inhibitor C-34. The NL4-3-derived strain was more than 500-fold resistant and contained a L33S mutation in gp41. 2003 Antiviral research Abstract HIV L33S 74 78 gp41 91 95 12898440 Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. In addition, most patients for whom the ddI-containing regimen failed lost the M184V/I mutation. 2003 The Journal of infectious diseases Abstract HIV M184I;M184V 79;79 86;86 12898440 Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. These results show that ddI continues to provide activity against viruses with the M184V/I mutation and suggest that the presence of the M184V/I mutation should not preclude the use of ddI in nucleoside-experienced patients. 2003 The Journal of infectious diseases Abstract HIV M184I;M184I;M184V;M184V 83;137;83;137 90;144;90;144 12902345 The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. In order to characterize the mechanism of this AZT resistance suppression, the Y181C substitution was introduced into both wild-type and AZT-resistant reverse transcriptase. 2003 The Journal of biological chemistry Abstract HIV Y181C 79 84 RT 151 172 12902345 The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. In this background of AZT resistance, additional "suppressive" substitutions such as Y181C restore sensitivity to AZT. 2003 The Journal of biological chemistry Abstract HIV Y181C 85 90 12902345 The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. Resistance to zidovudine (3'-azido-3'-deoxythymidine, AZT) by the human immunodeficiency virus, type 1, requires multiple amino acid substitutions such as D67N/K70R/T215F/K219Q in the viral reverse transcriptase (RT). 2003 The Journal of biological chemistry Abstract HIV D67N;K219Q;K70R;T215F 155;171;160;165 159;176;164;170 RT;RT 190;213 211;215 12902345 The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. The introduction of the Y181C substitution suppresses the increased repair (or unblocking) of the AZTMP-terminated primer provided by the AZT resistance substitutions in RT using either DNA or RNA templates, independently from the RT RNase H activity. 2003 The Journal of biological chemistry Abstract HIV Y181C 24 29 RT;RT 170;231 172;233 12902345 The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus, type 1, reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. When Y181C is added to the AZT resistance substitutions, ATP binds with less affinity to the AZTMP-terminated primer-RT binary complex. 2003 The Journal of biological chemistry Abstract HIV Y181C 5 10 RT 117 119 12904086 Atazanavir. The resistance profile of atazanavir is distinct, with an I50 L protease substitution appearing to be the signature mutation. 2003 Drugs Abstract HIV I50L 58 63 PR 64 72 12904355 Quality control trial for human immunodeficiency virus type 1 drug resistance testing using clinical samples reveals problems with detecting minority species and interpretation of test results. resistant minorities of L90M in the protease, which were determined to about 12% by real-time amplification, were only detected by one-fourth of the participants; (ii). 2003 Journal of clinical microbiology Abstract HIV L90M 24 28 PR 36 44 12908931 pol gene sequence variation in Swedish HIV-2 patients failing antiretroviral therapy. A M184V mutation indicative of lamivudine resistance was detected in three patients. 2003 AIDS research and human retroviruses Abstract HIV M184V 2 7 12908931 pol gene sequence variation in Swedish HIV-2 patients failing antiretroviral therapy. Instead, a E219D mutation evolved in virus from two patients and a Q151M mutation evolved in two other patients. 2003 AIDS research and human retroviruses Abstract HIV E219D;Q151M 11;67 16;72 12916058 Synthesis of novel MKC-442 analogues with potent activities against HIV-1. The most active compounds, N-1 cinnamyloxymethyl- and N-1 2-methyl-3-phenylallyloxymethyl substituted 5-ethyl-6-(3, 5-dimethylbenzyl)uracils (5b and 6b), showed activity against wild-type HIV-1 in the nanomolar range, and against Y181C andY181C+K103N, mutant strains known to be resistant to MKC-442, in the micromolar range. 2003 Archiv der Pharmazie Abstract HIV K103N;Y181C;Y181C 245;230;239 250;235;244 12917424 Non-nucleoside inhibitors of HIV-1 reverse transcriptase inhibit phosphorolysis and resensitize the 3'-azido-3'-deoxythymidine (AZT)-resistant polymerase to AZT-5'-triphosphate. Here we compared wild type and AZT-resistant (D67N/K70R/T215Y/K219Q) RTs for their ability to unblock the AZTMP-terminated primer by phosphorolysis in the presence of physiological concentrations of pyrophosphate or ATP. 2003 The Journal of biological chemistry Abstract HIV D67N;K219Q;K70R;T215Y 46;62;51;56 50;67;55;61 RT 69 72 12920196 Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S). Resistance was caused by a synergistic effect from both the F185K and C280S mutations. 2003 Molecular pharmacology Abstract HIV C280S;F185K 70;60 75;65 12920196 Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S). The F185K/C280S enzyme was markedly more active in the presence of manganese than magnesium. 2003 Molecular pharmacology Abstract HIV C280S;F185K 10;4 15;9 12920196 Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S). The F185K/C280S integrase was also relatively resistant to the same group of DKAs that were potent in the presence of magnesium with the wild-type enzyme. 2003 Molecular pharmacology Abstract HIV C280S;F185K 10;4 15;9 IN 16 25 12920196 Metal-dependent inhibition of HIV-1 integrase by beta-diketo acids and resistance of the soluble double-mutant (F185K/C280S). We compared the inhibition of HIV-1 integrase by six DKA derivatives using the wild-type enzyme or the double-mutant F185K/C280S, which has been previously used for crystal structure determinations. 2003 Molecular pharmacology Abstract HIV C280S;F185K 123;117 128;122 IN 36 45 12927307 Characterization of resistant HIV variants generated by in vitro passage with lopinavir/ritonavir. Passages with fixed 5/1 and 15/1 concentration ratios of LPV/r initially selected I84V and I50V/M46I mutants, respectively. 2003 Antiviral research Abstract HIV I50V;I84V;M46I 91;82;96 95;86;100 12927307 Characterization of resistant HIV variants generated by in vitro passage with lopinavir/ritonavir. Selection with LPV alone also generated the same initial mutants (I50V/M46I) as the 15/1 LPV/r passage. 2003 Antiviral research Abstract HIV I50V;M46I 66;71 70;75 12930892 A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding. In particular, two substitutions, M426L and M475I, are situated in the CD4 binding pocket of gp120. 2003 Proc Natl Acad Sci U S A Abstract HIV M426L;M475I 34;44 39;49 gp120 93 98 12930968 A positively charged side chain at position 154 on the beta8-alphaE loop of HIV-1 RT is required for stable ternary complex formation. Mutants carrying negatively charged side chains (K154D and K154E) were severely impaired in their polymerase function, while those with hydrophobic side chains (K154A and K154I) were moderately affected. 2003 Nucleic acids research Abstract HIV K154A;K154D;K154E;K154I 161;49;59;171 167;55;64;176 Pol 98 108 12936979 In vitro hypersusceptibility of human immunodeficiency virus type 1 subtype C protease to lopinavir. However, we did observe hypersusceptibility to lopinavir solely in clone C6, which includes the I93L substitution (a 2.6-fold decrease in the IC(50) compared to that for the subtype B reference strain). 2003 Antimicrobial agents and chemotherapy Abstract HIV I93L 96 100 12936979 In vitro hypersusceptibility of human immunodeficiency virus type 1 subtype C protease to lopinavir. In order to characterize the impact of genetic polymorphisms on the susceptibility of subtype C strains of human immunodeficiency virus type 1 to protease inhibitors (PIs), a subtype B protease that originated from an infectious clone was modified through site-directed mutagenesis to include the amino acid residue signatures of subtype C viruses (I15V, M36I, R41K, H69K, L89 M) with (clone C6) or without (clone C5) an I93L polymorphism present as a molecular signature of the worldwide subtype C protease. 2003 Antimicrobial agents and chemotherapy Abstract HIV H69K;I15V;I93L;L89M;M36I;R41K 367;349;421;373;355;361 371;353;425;378;359;365 PR;PR;PR;PI 146;185;499;167 154;193;507;170 12936979 In vitro hypersusceptibility of human immunodeficiency virus type 1 subtype C protease to lopinavir. The same phenotypic behavior was observed for 11 Brazilian and South African clinical isolates tested, in which only subtype C isolates carrying the I93L mutation presented significant hypersusceptibility to lopinavir. 2003 Antimicrobial agents and chemotherapy Abstract HIV I93L 149 153 12937000 Inhibition of human immunodeficiency virus by a new class of pyridine oxide derivatives. All compounds, including those pyridine oxide derivatives that inhibit both HIV-1 and HIV-2 replication, select for NNRTI-characteristic mutations in the HIV-1 reverse transcriptase of HIV-infected cell cultures (i.e., Lys103Asn, Val108Ile, Glu138Lys, Tyr181Cys and Tyr188His). 2003 Antimicrobial agents and chemotherapy Abstract HIV E138K;K103N;V108I;Y181C;Y188H 241;219;230;252;266 250;228;239;261;275 RT;NNRTI 160;116 181;121 HIV infections 185 197 12937000 Inhibition of human immunodeficiency virus by a new class of pyridine oxide derivatives. However, most compounds retained pronounced antiviral potency against virus strains that contained other NNRTI-characteristic RT mutations, such as Leu100Ile and Val179Asp. 2003 Antimicrobial agents and chemotherapy Abstract HIV L100I;V179D 148;162 157;171 NNRTI;RT 105;126 110;128 12941901 Human immunodeficiency virus type 1 protease regulation of tat activity is essential for efficient reverse transcription and replication. We altered the tat gene of the laboratory strain NL4-3 to Y47D and Y47N so that overlapping reading frames were not affected and showed that Y47D greatly diminished virus replication and conveyed a reverse transcription defect. 2003 Journal of virology Abstract HIV Y47D;Y47D;Y47N 58;141;67 62;145;71 RT;Tat 198;15 219;18 12941931 Parameters driving the selection of nelfinavir-resistant human immunodeficiency virus type 1 variants. Emergence of secondary mutations further increased the selective advantage of viruses harboring D30N. 2003 Journal of virology Abstract HIV D30N 96 100 12941931 Parameters driving the selection of nelfinavir-resistant human immunodeficiency virus type 1 variants. The advantage of the D30N mutant was mostly due to its resistance level, while the L90M mutation allowed preservation of infectivity coupled with minimal resistance. 2003 Journal of virology Abstract HIV D30N;L90M 21;83 25;87 12941931 Parameters driving the selection of nelfinavir-resistant human immunodeficiency virus type 1 variants. We investigated the parameters driving nelfinavir resistance, along the D30N and L90M evolutionary pathways. 2003 Journal of virology Abstract HIV D30N;L90M 72;81 76;85 12951121 Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase. A regression equation previously reported for the wild type (WT) enzyme is shown to predict 47 experimental activities for the K103N mutant with a q(2)=0.55 and avg error of only 0.46 kcal/mol. 2003 Bioorganic & medicinal chemistry letters Abstract HIV K103N 127 132 12951121 Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase. Further analysis identifies the key features for binding to the K103N mutant: ligand flexibility, burial of hydrophobic surface area, and protein-ligand van der Waals interactions. 2003 Bioorganic & medicinal chemistry letters Abstract HIV K103N 64 69 12951121 Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase. Monte Carlo-extended linear response (MC/ELR) calculations are used to examine the binding of efavirenz analogues with the K103N mutant of HIV-1 reverse transcriptase (HIVRT). 2003 Bioorganic & medicinal chemistry letters Abstract HIV K103N 123 128 RT 145 166 12953843 Prevalence of drug-resistant human immunodeficiency virus type 1 in therapy-naive patients and usefulness of genotype testing. We identified a patient who possessed a protease (PR) inhibitor-resistant HIV-1 with a major mutation consisting of L90M before the initiation of therapy. 2003 Microbiology and immunology Abstract HIV L90M 116 120 PR;PR 40;50 48;52 12956603 In silico structure-based design of a potent, mutation resilient, small peptide inhibitor of HIV-1 reverse transcriptase. Based on the crystal structures of the complexes of wild type RT and Tyr188Cys mutant of RT with UC-781, we have designed a small peptide inhibitor. 2003 Journal of biomolecular structure & dynamics Abstract HIV Y188C 69 78 RT;RT 62;89 64;91 12956603 In silico structure-based design of a potent, mutation resilient, small peptide inhibitor of HIV-1 reverse transcriptase. Docking results on this peptide using AutoDock3.0 and SYBYL 6.8.1 indicate that the peptide has a potency comparable to that of UC-781 with a retention of activity against the Tyr188Cys mutant RT. 2003 Journal of biomolecular structure & dynamics Abstract HIV Y188C 176 185 RT 193 195 12957189 Analysis of the protease sequences of HIV-1 infected individuals after Indinavir monotherapy. More prevalent detected mutations, thought to contribute to antiretroviral resistance, were L63P (42%), L10I (35%), M36I (30%), V82A/T/F (26%). 2003 Journal of clinical virology Abstract HIV L10I;L63P;M36I;V82A;V82F;V82T 104;92;116;128;128;128 108;96;120;136;136;136 12960821 Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. At week 96, among the switchers, i.e., group A d4T/ddI to ZDV/3TC, group B ZDV/3TC to d4T/ddI, and group C ZDV/3TC/ddI to d4T/3TC/abacavir: NAM, 12/21 (57%), 4/7 and 1/3; Q151M, 4/21 (19%), 0% and 1/3, respectively. 2003 AIDS (London, England) Abstract HIV Q151M 171 176 12960821 Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. CONCLUSIONS: Multi-NRTI resistance (NAM and Q151M) and M184V (only in 3TC failure) are commonly found in HIV-1 subtype A/E infection associated with NRTI failure. 2003 AIDS (London, England) Abstract HIV M184V;Q151M 55;44 60;49 NRTI;NRTI 19;149 23;153 12960821 Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. RESULTS: Resistance mutations found in the d4T/ddI, ZDV/3TC, and ZDV/3TC/ddI groups: none at baseline; at week 48, nucleoside analogue mutations (NAM), 2/17 (12%), 2/10 (20%), and 1/8; Q151M complex, 3/17 (18%), 0%, and 0%; M184V, 0%, 10/10 (P < 0.001), 3/8; V75T, 3/17 (18%), 0%, and 0%; L74V, 3/7 (18%), 0%, and 0%, respectively. 2003 AIDS (London, England) Abstract HIV L74V;M184V;Q151M;V75T 289;224;185;259 293;229;190;263 12960821 Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors. Suboptimal d4T/ddI therapy led to a high incidence of V75T and L74V mutations. 2003 AIDS (London, England) Abstract HIV L74V;V75T 63;54 67;58 13130407 Tenofovir disoproxil fumarate. The signature mutation is the K65R mutation, which causes variable loss in susceptibility to tenofovir DF, didanosine, and abacavir. 2003 Clinical infectious diseases Abstract HIV K65R 30 34 1315755 Mutations that alter the activity of the Rous sarcoma virus protease. Changing histidine 65 to glycine (H65G) gave an inactive enzyme, while a double mutant R105P,G106V, as well as the triple mutant, H65G,R105P,G106V, produced enzymes which showed significant activity toward a substrate that represented a HIV-1 cleavage site. 1992 The Journal of biological chemistry Abstract HIV G106V;G106V;H65G;H65G;H65G;R105P;R105P 141;93;130;34;9;87;135 146;98;134;38;32;92;140 1315755 Mutations that alter the activity of the Rous sarcoma virus protease. In contrast, the substitution A40S was active, but showed a reduced rate of catalysis. 1992 The Journal of biological chemistry Abstract HIV A40S 30 34 1315755 Mutations that alter the activity of the Rous sarcoma virus protease. Mutating the catalytic aspartate (D37S) or an adjacent conserved alanine to threonine (A40T), produced inactive enzymes. 1992 The Journal of biological chemistry Abstract HIV A40T;D37S 87;34 91;38 1315755 Mutations that alter the activity of the Rous sarcoma virus protease. Mutations in the flaps of conserved glycines (G69L, G70L) produced inactive PRs. 1992 The Journal of biological chemistry Abstract HIV G69L;G70L 46;52 50;56 PR 76 79 1371691 Nonnucleoside inhibitors of HIV-1 reverse transcriptase: nevirapine as a prototype drug. Cell culture selection in the continued presence of nevirapine results in the appearance of resistant HIV-1, Tyr 181 to Cys, raising the concern that combination drug therapy will be required in the clinic. 1992 AIDS research and human retroviruses Abstract HIV Y181C 109 123 1371886 Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. Using an HIV marker rescue system, we have mapped and identified a fifth mutation conferring resistance to zidovudine, namely, methionine to leucine at codon 41 of HIV RT. 1992 Proc Natl Acad Sci U S A Abstract HIV M41L 127 160 RT 168 170 1382052 Functional analysis of novel selective mutants of the reverse transcriptase of human immunodeficiency virus type 1. 3) A mutant of HIV-1 RT in which a cysteine residue substituted for alanine 446, was found to be slightly hyperactive for both DNA polymerase and RNase H activities. 1992 The Journal of biological chemistry Abstract HIV C446A 35 79 Pol;RT 131;21 141;23 1409671 Mutational analysis of the integrase protein of human immunodeficiency virus type 2. Three mutants in this region (Asn-117-->Ile, Asn-120-->Leu, and Lys-159-->Val) were inhibited in strand transfer but were inhibited less strongly in donor cut. 1992 Proc Natl Acad Sci U S A Abstract HIV N117I 30 43 1409671 Mutational analysis of the integrase protein of human immunodeficiency virus type 2. We found three mutations that (almost) totally abolished IN function: Asp-64-->Val, Asp-116-->Ile, and Glu-152-->Leu, whereas 25 mutations did not affect IN function. 1992 Proc Natl Acad Sci U S A Abstract HIV D64V 70 82 Asp;Asp;IN;IN 70;84;57;154 73;87;59;156 14501800 Identification and distribution of HIV type 1 genetic diversity and protease inhibitor resistance-associated mutations in Shanghai, P. R. China. Substitutions characteristic with the subtype B/B' sequences mainly among hemophiliacs included L63P (87%), A71V/T (27%), and V77I (93%) while those that characterized the non-B sequences mainly found among heterosexuals included M36I (69%) and K20R (19%). 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A71T;A71V;K20R;L63P;M36I;V77I 108;108;245;96;230;126 114;114;249;100;234;130 14506268 Pro-apoptotic activity of HIV-1 auxiliary regulatory protein Vpr is subtype-dependent and potently enhanced by nonconservative changes of the leucine residue at position 64. However, the L64P mutation efficiently enhances the pro-apoptotic potential of the subtype B and subtype D Vpr molecules but not that of the A/G recombinant Vpr. 2003 The Journal of biological chemistry Abstract HIV L64P 13 17 Vpr;Vpr 107;157 110;160 14506268 Pro-apoptotic activity of HIV-1 auxiliary regulatory protein Vpr is subtype-dependent and potently enhanced by nonconservative changes of the leucine residue at position 64. The pro-apoptotic activity of the VprL64P mutant also requires activation of caspase(s) and is inhibited by the secondary mutation I61A, indicating a high specificity for Vpr-induced apoptosis. 2003 The Journal of biological chemistry Abstract HIV I61A 131 135 Vpr;Vpr 34;171 37;174 14512553 Replication of chimeric human immunodeficiency virus type 1 (HIV-1) containing HIV-2 integrase (IN): naturally selected mutations in IN augment DNA synthesis. Analysis of clones derived from the CF-131 virus indicated the selection of two additional IN mutations, Q96H and K127E, and a fixed V179I RT mutation. 2003 Journal of virology Abstract HIV K127E;Q96H;V179I 114;105;133 119;109;138 IN;RT 91;139 93;141 14512553 Replication of chimeric human immunodeficiency virus type 1 (HIV-1) containing HIV-2 integrase (IN): naturally selected mutations in IN augment DNA synthesis. Sequence analysis of multiple clones derived from the CF-65 virus culture demonstrated a diversity of mutations in the reverse transcriptase (RT) and a common V204I IN mutation. 2003 Journal of virology Abstract HIV V204I 159 164 RT;IN;RT 119;165;142 140;167;144 14512553 Replication of chimeric human immunodeficiency virus type 1 (HIV-1) containing HIV-2 integrase (IN): naturally selected mutations in IN augment DNA synthesis. The Q96H and K127E mutations are present in adjacent helical structures on the surface of the IN protein and together account for most of the increase observed in DNA synthesis. 2003 Journal of virology Abstract HIV K127E;Q96H 13;4 18;8 IN 94 96 14512553 Replication of chimeric human immunodeficiency virus type 1 (HIV-1) containing HIV-2 integrase (IN): naturally selected mutations in IN augment DNA synthesis. This analysis revealed that the Q96H, K127E and V204I mutations increased the infectivity of the chimeric virus by augmenting the initiation of viral cDNA synthesis in infected cells. 2003 Journal of virology Abstract HIV K127E;Q96H;V204I 38;32;48 43;36;53 14513419 Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. Drugs were grouped by the effect of the M184V mutation: susceptibility to group 1 drugs (zidovudine, stavudine, tenofovir, and adefovir) increased when M184V was present, whereas susceptibility to group 2 drugs (didanosine, zalcitabine, abacavir, and lamivudine) decreased. 2003 The Journal of infectious diseases Abstract HIV M184V;M184V 40;152 45;157 14513419 Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. Significant cross-resistance was observed among all NRTIs and was most notable when samples with or without M184V were analyzed separately. 2003 The Journal of infectious diseases Abstract HIV M184V 108 113 NRTI 52 57 14513419 Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. The modulating effect of M184I/V on drug susceptibility was present regardless of the number of TAMs. 2003 The Journal of infectious diseases Abstract HIV M184I;M184V 25;25 32;32 14517075 Deletion of stem-loop 3 is compensated by second-site mutations within the Gag protein of human immunodeficiency virus type 1. Similar studies are now extended to SL3 and the results demonstrate that deletion of this RNA structure is rescued by two point mutations, i.e., A11V in p2 and I12V in nucleocapsid (NC). 2003 Virology Abstract HIV A11V;I12V 145;160 149;164 NC 182 184 14517075 Deletion of stem-loop 3 is compensated by second-site mutations within the Gag protein of human immunodeficiency virus type 1. Therefore, the positive effects of A11V and I12V on dimerization of the SL3-deleted RNA must have taken place at the maturation stage. 2003 Virology Abstract HIV A11V;I12V 35;44 39;48 14517075 Deletion of stem-loop 3 is compensated by second-site mutations within the Gag protein of human immunodeficiency virus type 1. These defects are corrected by the compensatory mutations A11V and I12V. 2003 Virology Abstract HIV A11V;I12V 58;67 62;71 14518705 High incidence of non-B and recombinant HIV-1 strains in newly diagnosed patients in Galicia, Spain: study of genotypic resistance. Five of 85 patients (5.9%), all infected with B subtype viruses, showed resistance-associated mutations in RT (M184V, M41L, L210W, T215Y/D and K219Q). 2003 Antiviral therapy Abstract HIV K219Q;L210W;M184V;M41L;T215D;T215Y 143;124;111;118;131;131 148;129;116;122;138;138 RT 107 109 14518705 High incidence of non-B and recombinant HIV-1 strains in newly diagnosed patients in Galicia, Spain: study of genotypic resistance. In one patient (1.2%) infected with a subtype G strain, resistance-associated mutations in PR (K20I+M36I+M46I+V82I) were detected. 2003 Antiviral therapy Abstract HIV K20I;M36I;M46I;V82I 95;100;105;110 99;104;109;114 PR 91 93 14518705 High incidence of non-B and recombinant HIV-1 strains in newly diagnosed patients in Galicia, Spain: study of genotypic resistance. Several polymorphisms in RT: D123S, Q174K, D177E, T200A, V245Q, and PR: I13V, K20I, M36I, R41K, H69K, L89M were detected more frequently in non-B and recombinants than in B strains (P<0.01 to P<0.001). 2003 Antiviral therapy Abstract HIV D123S;D177E;H69K;I13V;K20I;L89M;M36I;Q174K;R41K;T200A;V245Q 29;43;96;72;78;102;84;36;90;50;57 34;48;100;76;82;106;88;41;94;55;62 PR;RT 68;25 70;27 14522102 Mutation patterns of the reverse transcriptase genes in HIV-1 infected patients receiving combinations of nucleoside and non nucleoside inhibitors. Among mutations correlated to high (K103N, V106A, Y181C/I, Y188C/H/L, G190A/C/E/Q/S/T) or moderate (V108I, V118I) levels of nevirapine resistance, the predominant amino acid change was a substitution at 103 codon, present in 24 of 80 samples tested. 2003 International journal of antimicrobial agents Abstract HIV G190A;G190C;G190E;G190Q;G190S;G190T;K103N;V106A;V108I;V118I;Y181C;Y181I;Y188C;Y188H;Y188L 70;70;70;70;70;70;36;43;100;107;50;50;59;59;59 85;85;85;85;85;85;41;48;105;112;57;57;68;68;68 14522102 Mutation patterns of the reverse transcriptase genes in HIV-1 infected patients receiving combinations of nucleoside and non nucleoside inhibitors. Finally Q151M, the marker mutation able to confer resistance to all nucleoside analogues, was detected in seven patients with a viral load of between 1 x 10(4) and 9 x 10(4) HIV-1 RNA copies/ml. 2003 International journal of antimicrobial agents Abstract HIV Q151M 8 13 14522102 Mutation patterns of the reverse transcriptase genes in HIV-1 infected patients receiving combinations of nucleoside and non nucleoside inhibitors. Mutations (M184V or M184I) conferring resistance to lamivudine were detected in an extremely high percentage of patients (61%). 2003 International journal of antimicrobial agents Abstract HIV M184I;M184V 20;11 25;17 14522102 Mutation patterns of the reverse transcriptase genes in HIV-1 infected patients receiving combinations of nucleoside and non nucleoside inhibitors. The frequencies of T215S/Y/F, M41L, D67N, L210W K70R, K219Q mutations, detectable in plasma samples, conferring resistance to zidovudine were 61.2, 56.2, 36.2, 31.5, 27.5 and 17.5%, respectively. 2003 International journal of antimicrobial agents Abstract HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215S;T215Y 36;54;48;42;30;19;19;19 40;59;52;47;34;28;28;28 14522102 Mutation patterns of the reverse transcriptase genes in HIV-1 infected patients receiving combinations of nucleoside and non nucleoside inhibitors. The relationship between the genotype and the viral load showed that the incidence of some specific mutations [M41L, T215Y (correlated to zidovudine resistance) and K103N (correlated to all NNRTIs drugs)] significantly (P=0.001) increased with higher viral load. 2003 International journal of antimicrobial agents Abstract HIV K103N;M41L;T215Y 165;111;117 170;115;122 NNRTI 190 196 14551187 Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. Additionally, we report how the decreased viral replication capacity of resistant viruses is directly linked to their decreased ability to use natural nucleotide substrates and that combination of the K65R and M184V resistance mutations leads to greater decreases in viral replication capacity. 2004 The Journal of biological chemistry Abstract HIV K65R;M184V 201;210 205;215 14551187 Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. We report the molecular mechanisms by which a virus resistant to lamivudine with the M184V reverse transcriptase mutation shows increased susceptibility to tenofovir and can suppress the effects of the tenofovir resistance mutation K65R. 2004 The Journal of biological chemistry Abstract HIV K65R;M184V 232;85 236;90 RT 91 112 14557631 Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. However, 3' processing and strand transfer activities of the recombinant integrases with two (T66I L74M) and three (T66I L74M S230R) mutations were notably lower than those of the wild-type integrase. 2003 Journal of virology Abstract HIV L74M;L74M;S230R;T66I;T66I 99;121;126;94;116 103;125;131;99;121 IN;IN 73;190 83;199 14557631 Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. The mutations T66I, L74M, and S230R emerged successively in the integrase gene. 2003 Journal of virology Abstract HIV L74M;S230R;T66I 20;30;14 24;35;18 IN 64 73 14557631 Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. The virus with three mutations (T66I L74M S230R) was 10-fold less susceptible to L-708,906, while displaying the sensitivity of the wild-type virus to inhibitors of the RT or PRO or viral entry process. 2003 Journal of virology Abstract HIV L74M;S230R;T66I 37;42;32 41;47;37 RT 169 171 14561099 Inhibition of human immunodeficiency virus reverse transcriptase by synadenol triphosphate and its E-isomer. The extent of inhibition of two mutant forms of reverse transcriptase (RT), RT(M184V) and RT(M184I), with triphosphate 1c was about 5 and 8 times lower than that of wild-type RT(wt). 2003 Journal of medicinal chemistry Abstract HIV M184I;M184V 93;79 98;84 RT;RT;RT;RT;RT 48;71;76;90;175 69;73;78;92;177 14563897 HIV susceptibility to amprenavir: phenotype-based versus rules-based interpretations. Mutation I84V and accumulation of >3 PAMs were found to be associated with resistance as interpreted with all systems tested. 2003 The Journal of antimicrobial chemotherapy Abstract HIV I84V 9 13 14563897 HIV susceptibility to amprenavir: phenotype-based versus rules-based interpretations. Only the I84V mutation was almost invariably found in concordant resistant isolates compared with S/R isolates (60% versus 0%, respectively; P < 0.0001). 2003 The Journal of antimicrobial chemotherapy Abstract HIV I84V 9 13 14565238 2'-Fluoro-4'-thio-2',3'-unsaturated nucleosides: anti-HIV activity, resistance profile, and molecular modeling studies. Both D- and L-2'-fluoro-4'-thio-2',3'-unsaturated nucleosides were synthesized and their anti-HIV activity against the drug sensitive virus and lamivudine-resistant mutant (M184V) were evaluated. 2003 Nucleosides, nucleotides & nucleic acids Abstract HIV M184V 173 178 14565328 In vitro study of resistance-associated genotypic mutations to nucleoside analogs. Our studies was not revealed substitution at position 75 for ph-AZT resistant variants, whereas substitution at position L214F have been observed in both experiments using AZT and ph-AZT. 2003 Nucleosides, nucleotides & nucleic acids Abstract HIV L214F 121 126 14565328 In vitro study of resistance-associated genotypic mutations to nucleoside analogs. Selected AZT resistant variants contained amino acid substitutions in positions D67A and K70R. 2003 Nucleosides, nucleotides & nucleic acids Abstract HIV D67A;K70R 80;89 84;93 14565328 In vitro study of resistance-associated genotypic mutations to nucleoside analogs. Selected d4T resistant mutants contained amino acid substitutions in positions N54D and P52R. 2003 Nucleosides, nucleotides & nucleic acids Abstract HIV N54D;P52R 79;88 83;92 14565328 In vitro study of resistance-associated genotypic mutations to nucleoside analogs. Selected ddI resistant mutants contained only one amino acid substitution in position P143S. 2003 Nucleosides, nucleotides & nucleic acids Abstract HIV P143S 86 91 14565609 Antiretroviral therapy in HIV-2-infected patients: changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of patients treated in Abidjan, Cote d'Ivoire. Three patients had the multi-drug-resistant mutation, Q151M, two of whom showed reduced susceptibility to zidovudine, didanosine, stavudine and zalcitabine. 2003 AIDS (London, England) Abstract HIV Q151M 54 59 14565610 Clinical, immunological and virological response to different antiretroviral regimens in a cohort of HIV-2-infected patients. Development of mutations proved to be similar to that observed in HIV-1-infected patients, with the exception of a higher occurrence of the Q151M mutation within the reverse transcriptase gene. 2003 AIDS (London, England) Abstract HIV Q151M 140 145 RT 166 187 HIV infections 66 80 14571185 Lack of persistent drug-resistant mutations evaluated within and between treatment interruptions in chronically HIV-1-infected patients. In the remaining six patients, the following patterns of mutations associated with viral resistance were found: one mutation (K70R), which was observed in one patient during the 1st TI and persisted during follow-up; two mutations (L90M, M184V), which were observed in four patients during the 1st TI and were intermittently present or lost following extended TI, treatment reinitiation and/or during subsequent TI; and evolution of two mutations (M184V, K219E) observed in two patients. 2003 AIDS (London, England) Abstract HIV K219E;K70R;L90M;M184V;M184V 455;126;232;238;448 460;130;236;243;453 14585205 Drug resistance profiles of recombinant reverse transcriptases from human immunodeficiency virus type 1 subtypes A/E, B, and C. Subtype C variants containing the novel V106M resistance codon showed cross-resistance to all approved NNRTIs in cell-free RT assays. 2003 AIDS research and human retroviruses Abstract HIV V106M 40 45 NNRTI;RT 103;123 109;125 14585332 Mutations in the C3 region of human and simian immunodeficiency virus envelope have differential effects on viral infectivity, replication, and CD4-dependency. However, substitutions of D385, which is critical for CD4 engagement along with other changes such as G382R, G383R, frequently arise in SIV mac-infected macaques. 2003 Virology Abstract HIV G382R;G383R 102;109 107;114 14585332 Mutations in the C3 region of human and simian immunodeficiency virus envelope have differential effects on viral infectivity, replication, and CD4-dependency. In contrast, mutation of D368N resulted in a virus that could not spread in cells expressing low levels of CD4, but which replicated efficiently when high levels of CD4 were expressed. 2003 Virology Abstract HIV D368N 25 30 14585332 Mutations in the C3 region of human and simian immunodeficiency virus envelope have differential effects on viral infectivity, replication, and CD4-dependency. Mutations flanking the C3 region such as G382R or V388A enhanced and changes within the C3 region (i.e., G383R or D385N) impaired SIVmac infectivity. 2003 Virology Abstract HIV D385N;G382R;G383R;V388A 114;41;105;50 119;46;110;55 14585332 Mutations in the C3 region of human and simian immunodeficiency virus envelope have differential effects on viral infectivity, replication, and CD4-dependency. Substitutions of S365R and D368G in the HIV-1 Env, which correspond to G382 and D385 in SIVmac Env, consistently impaired viral infectivity. 2003 Virology Abstract HIV D368G;S365R 27;17 32;22 Env;Env 46;95 49;98 14585332 Mutations in the C3 region of human and simian immunodeficiency virus envelope have differential effects on viral infectivity, replication, and CD4-dependency. We conclude that substitutions flanking the C3 region in SIVmac Env such as G382R or V388A represent one step toward adaptation to growth in target cells expressing low CD4 levels, whereas changes within the C3 region that disrupt CD4 binding might indicate the emergence of CD4-independent variants at later stages of infection, which could potentially broaden viral tropism. 2003 Virology Abstract HIV G382R;V388A 76;85 81;90 Env 64 67 14592498 Studies of molecular mechanism of tenofovir against 3TC- and AZT-resistance mutant HIV-1 reverse transcriptase. TFV-DP is located far away from the bulky side chain of Val184 in M184V RT and tenofovir is readily translocated without steric hindrance with Asp185 after incorporation into the growing primer chain complexed with AZT-resistant RT. 2003 Bioorganic & medicinal chemistry letters Abstract HIV M184V 66 71 Asp;RT;RT 143;72;229 146;74;231 14595464 Human immunodeficiency virus type 1: drug resistance in treated and untreated Brazilian children. Eight were susceptible to NRTIs and all of them were susceptible to PIs; one presented the V108I mutation, which confers low-level resistance to NNRTIs. 2003 Memorias do Instituto Oswaldo Cruz Abstract HIV V108I 91 96 NNRTI;NRTI;PI 145;26;68 151;31;71 14599015 Synthesis and evaluation of new potential HIV-1 non-nucleoside reverse transcriptase inhibitors. New analogues of MKC-442 containing Michael acceptors in the C-6 position. Analogues of MKC-442 capable of undergoing Michael addition reactions were synthesised in order to investigate the activity against the HIV-1 mutant (Y181C). 2003 Organic & biomolecular chemistry Abstract HIV Y181C 150 155 14599015 Synthesis and evaluation of new potential HIV-1 non-nucleoside reverse transcriptase inhibitors. New analogues of MKC-442 containing Michael acceptors in the C-6 position. However, no activity was observed against the Y181C mutant. 2003 Organic & biomolecular chemistry Abstract HIV Y181C 46 51 14605126 Novel enzyme-linked minisequence assay for genotypic analysis of human immunodeficiency virus type 1 drug resistance. ELMA is a combination of hybridization and a 1-base extension reaction, and we designed the assay to detect five mutations conferring nucleoside analogue resistance (M41L, D67N, K70R, T215Y, and M184V) and six mutations conferring protease inhibitor resistance (D30N, M46I, G48V, V82A, I84V, and L90M). 2003 Journal of clinical microbiology Abstract HIV D30N;D67N;G48V;I84V;K70R;L90M;M184V;M41L;M46I;T215Y;V82A 262;172;274;286;178;296;195;166;268;184;280 266;176;278;290;182;300;200;170;272;189;284 PR 231 239 14610180 Simian-human immunodeficiency virus escape from cytotoxic T-lymphocyte recognition at a structurally constrained epitope. An analysis of the SIV and HIV-2 sequences from the Los Alamos HIV Sequence Database revealed a significant association between any position 2 p11C, C-M epitope mutation and the I71V mutation. 2003 Journal of virology Abstract HIV I71V 178 182 14610180 Simian-human immunodeficiency virus escape from cytotoxic T-lymphocyte recognition at a structurally constrained epitope. Here we demonstrate that the emergence of a position 2 p11C, C-M epitope substitution (T47I) in a simian-human immunodeficiency virus (SHIV) strain 89.6P-infected Mamu-A(*)01(+) monkey is temporally correlated with the emergence of a flanking isoleucine-to-valine substitution at position 71 (I71V) of the capsid protein. 2003 Journal of virology Abstract HIV I71V;I71V;T47I 293;243;87 297;291;91 Capsid 306 312 14610180 Simian-human immunodeficiency virus escape from cytotoxic T-lymphocyte recognition at a structurally constrained epitope. The T47I mutation alone is associated with significant decreases in viral protein expression, infectivity, and replication, and these deficiencies are restored to wild-type levels with the introduction of the flanking I71V mutation. 2003 Journal of virology Abstract HIV I71V;T47I 218;4 222;8 14616723 New patterns of HIV-1 resistance during HAART. Nucleoside analog mutations (NAMs) (M41L, D67N, K70R, L210W, T215Y/F and K219Q/E) are associated with reduced susceptibility to most nucleoside analogs and the nucleotide tenofovir. 2003 Clinical microbiology and infection Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 42;73;73;48;54;36;61;61 46;80;80;52;59;40;68;68 14616723 New patterns of HIV-1 resistance during HAART. This recently approved drug has shown a reduced virologic response in the presence of three or more NAMs, including M41L or L210W, as well as in the presence of T69 insertions. 2003 Clinical microbiology and infection Abstract HIV L210W;M41L 124;116 129;120 14622012 Multidrug resistance to HIV-1 protease inhibition requires cooperative coupling between distal mutations. A mutant containing only the four active site mutations (V82A/I84V/M46I/I54V) only showed a small cooperative effect, suggesting that the mutations at the dimer interface (L10I/L90M) play a major role in eliciting a cooperative response. 2003 Biochemistry Abstract HIV V82A;I54V;I84V;M46I;L10I;L90M 57;72;62;67;172;177 61;76;66;71;176;181 14622012 Multidrug resistance to HIV-1 protease inhibition requires cooperative coupling between distal mutations. This mutant (MDR-HM) contains six amino acid mutations (L10I/M46I/I54V/V82A/I84V/L90M) located within and outside the active site of the enzyme. 2003 Biochemistry Abstract HIV L10I;I54V;I84V;L90M;M46I;V82A 56;66;76;81;61;71 60;70;80;85;65;75 14622012 Multidrug resistance to HIV-1 protease inhibition requires cooperative coupling between distal mutations. To understand the origin of resistance, three submutants containing mutations in specific regions were also studied, i.e., the active site (V82A/I84V), flap region (M46I/I54V), and dimerization region (L10I/L90M). 2003 Biochemistry Abstract HIV L10I;M46I;V82A;I54V;I84V;L90M 202;165;140;170;145;207 206;169;144;174;149;211 14624368 Emergence of minor populations of human immunodeficiency virus type 1 carrying the M184V and L90M mutations in subjects undergoing structured treatment interruptions. In 14 of 25 and in 3 of 25 subjects, the M184V and the L90M mutations, respectively, were detected as minor populations, at different times during STI. 2003 The Journal of infectious diseases Abstract HIV L90M;M184V 55;41 59;46 14624368 Emergence of minor populations of human immunodeficiency virus type 1 carrying the M184V and L90M mutations in subjects undergoing structured treatment interruptions. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction, by use of allele-discriminating oligonucleotides for 2 key resistance mutations: L90M (protease) and M184V (reverse transcriptase). 2003 The Journal of infectious diseases Abstract HIV L90M;M184V 193;213 197;218 RT;Pol;PR 220;85;199 241;95;207 14628280 Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes. BACKGROUND: Multiple resistance to nucleoside analogs mediated by the Q151M complex and/or codon 67-69 inserts/deletions represents a growing problem among HIV-infected persons, most of whom have been exposed to sequential therapies for long periods of time. 2003 HIV clinical trials Abstract HIV Q151M 70 75 HIV infections 156 168 14628280 Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes. No differences were found when patients with Q151M and codon 67-69 rearrangements were compared. 2003 HIV clinical trials Abstract HIV Q151M 45 50 14628280 Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes. Twelve of them carried the Q151M complex and 9 harbored different codon 67-69 inserts. 2003 HIV clinical trials Abstract HIV Q151M 27 32 14633983 The phosphorylation state of an autoregulatory domain controls PACS-1-directed protein traffic. Moreover, the Ser278-->Ala mutation yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of PACS-1-regulated cargo molecules to the TGN. 2003 The EMBO journal Abstract HIV S278A 14 26 14633983 The phosphorylation state of an autoregulatory domain controls PACS-1-directed protein traffic. Phosphorylation of Ser278 by CK2 or a Ser278-->Asp mutation increased the interaction between PACS-1 and cargo, whereas a Ser278-->Ala substitution decreased this interaction. 2003 The EMBO journal Abstract HIV S278A;S278D 122;38 134;50 Asp 47 50 14640388 Drug resistance mutations during structured treatment interruptions. Among the 74 patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%) patients. 2003 Antiviral therapy Abstract HIV M184I;M184V 48;48 55;55 14640388 Drug resistance mutations during structured treatment interruptions. CONCLUSIONS: The M184V/I mutation is frequently selected during repeated treatment interruptions. 2003 Antiviral therapy Abstract HIV M184I;M184V 17;17 24;24 14640388 Drug resistance mutations during structured treatment interruptions. The relative risk for virological failure was 2.55-fold higher in patients with the M184V/I mutation than in patients without detectable mutation (P=0.007). 2003 Antiviral therapy Abstract HIV M184I;M184V 84;84 91;91 14640682 Role of the fusion peptide and membrane-proximal domain in HIV-1 envelope glycoprotein-mediated membrane fusion. (1) A Glu residue at position 2 of the gp41 fusion peptide is substituted for Val (V2E) to produce one mutant. 2003 Biochemistry Abstract HIV V2E 83 86 gp41 39 43 14640682 Role of the fusion peptide and membrane-proximal domain in HIV-1 envelope glycoprotein-mediated membrane fusion. The V2E Env did not mediate membrane destabilization. 2003 Biochemistry Abstract HIV V2E 4 7 Env 8 11 14644507 The lethal phenotype observed after HIV-1 integrase expression in yeast cells is related to DNA repair and recombination events. Genetic experiments were designed to show that both the mutagenic effect and the level of recombination events were affected in cells expressing the active retroviral enzyme, while expression of the mutated inactive IN D116A has no significant effect. 2003 Gene Abstract HIV D116A 219 224 IN 216 218 14645322 Relationships among various nucleoside resistance-conferring mutations in the reverse transcriptase of HIV-1. These resistant strains may often suffer from a replication disadvantage in comparison with wild-type viruses when grown in the absence of drug pressure and a potential benefit in this regard has been shown for lamivudine-resistant viruses that contain a M184V mutation in reverse transcriptase, as well as for several other drug-resistant viral variants. 2004 The Journal of antimicrobial chemotherapy Abstract HIV M184V 255 260 RT 273 294 14651977 Mutations in gp41 and gp120 of HIV-1 isolates resistant to hexa-arginine neomycin B conjugate. We found in the NeoR6-resistant isolates the following mutations in gp120: I339T in the C3 region, S372L in the V4 region, and Q395K in the C4 region; and in gp41: S668R and F672Y in the 'heptad repeat' 2 (HR2) region. 2003 Biochemical and biophysical research communications Abstract HIV F672Y;I339T;Q395K;S372L;S668R 174;75;127;99;164 179;80;132;104;169 gp120;gp41 68;158 73;162 14657764 Epidemiologic and molecular characterization of human immunodeficiency virus type 1 in southern Brazil. Comparison of subtype C-infected treated and untreated subjects revealed amino acid differences in protease and RT, especially in the RT mutation D/G123S. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D123S;G123S 146;146 153;153 PR;RT;RT 99;112;134 107;114;136 14657764 Epidemiologic and molecular characterization of human immunodeficiency virus type 1 in southern Brazil. The overall analysis of drug resistance mutations in viruses from treated subjects has highlighted some associations between subtypes and particular mutations, such as V82A/F/T/S in protease and subtype F1 and M41L and L210W in RT and subtype B. 2003 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L210W;M41L;V82A;V82F;V82S;V82T 219;210;168;168;168;168 224;214;178;178;178;178 PR;RT 182;228 190;230 14661176 Comparison of wild-type and class I integrase mutant-FIV vectors in retina demonstrates sustained expression of integrated transgenes in retinal pigment epithelium. A second group received subretinal injections of either WT vector or equivalent D66V vector (reverse transcriptase-normalized to WT), and were analyzed after 2, 3 and 7 months. 2003 The journal of gene medicine Abstract HIV D66V 80 84 RT 93 114 14661176 Comparison of wild-type and class I integrase mutant-FIV vectors in retina demonstrates sustained expression of integrated transgenes in retinal pigment epithelium. The sustained retinal expression produced by subretinally injected vector was blocked by the D66V mutation. 2003 The journal of gene medicine Abstract HIV D66V 93 97 14661176 Comparison of wild-type and class I integrase mutant-FIV vectors in retina demonstrates sustained expression of integrated transgenes in retinal pigment epithelium. We also compared the wild-type (WT) vector with one incorporating a single class I amino acid mutation in FIV integrase (D66V). 2003 The journal of gene medicine Abstract HIV D66V 121 125 IN 110 119 14670585 No cross-resistance or selection of HIV-1 resistant mutants in vitro to the antiretroviral tripeptide glycyl-prolyl-glycine-amide. However, one mutation (T107I) in the p24 gene was detected in both series, but this mutation was not associated with decreased sensitivity to GPG-NH(2). 2004 Antiviral research Abstract HIV T107I 23 28 p24 37 40 14675866 Unusual codon 69 insertions: influence on human immunodeficiency virus type 1 reverse transcriptase drug susceptibility. Moreover, all three samples had a T69S substitution followed by three different dual amino acid insertions: SG, TG and VG. 2004 Journal of clinical virology Abstract HIV T69S 34 38 14675866 Unusual codon 69 insertions: influence on human immunodeficiency virus type 1 reverse transcriptase drug susceptibility. Patient 001 presented a pattern that should not cause a high phenotypic resistance to 3TC per se, and so we can argue that the concomitant presence of the insertion T69S (SG) makes this isolate moderately resistant to this drug. 2004 Journal of clinical virology Abstract HIV T69S 165 169 14683659 Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression. Four of these five patients had either the K65R mutation, the M184V/I mutation, or both. 2003 Lancet (London, England) Abstract HIV K65R;M184I;M184V 43;62;62 47;69;69 14689353 Progressive reversion of human immunodeficiency virus type 1 resistance mutations in vivo after transmission of a multiply drug-resistant virus. Reversion of the M184V mutation alone did not change viral replicative capacity (RC), but it led to enhanced resistance to zidovudine and tenofovir. 2003 Clinical infectious diseases Abstract HIV M184V 17 22 14690411 Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. M36I and A71V, when present as natural polymorphisms, could aid the virus in developing active site mutations to escape inhibitor binding while maintaining catalytic efficiency. 2003 Biochemistry Abstract HIV A71V;M36I 9;0 13;4 14690411 Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. Our study shows that the M36I and A71V mutations provide a greater level of inhibitor cross-resistance combined with active site mutation D30N. 2003 Biochemistry Abstract HIV A71V;D30N;M36I 34;138;25 38;142;29 14690411 Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. The double mutants containing a combination of mutations D30N, M36I, and A71V displayed -0.5-fold to +6-fold changes in the K(i) of all inhibitors tested, with ritonavir and nelfinavir most affected. 2003 Biochemistry Abstract HIV A71V;D30N;M36I 73;57;63 77;61;67 14690411 Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. The variant containing mutation D30N displayed a 2-6-fold increase in K(i) for all inhibitors tested, with nelfinavir showing the greatest increase. 2003 Biochemistry Abstract HIV D30N 32 36 14690411 Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. Variants containing M36I or A71V alone did not display a significant change in binding affinities to the inhibitors tested. 2003 Biochemistry Abstract HIV A71V;M36I 28;20 32;24 14690411 Secondary mutations M36I and A71V in the human immunodeficiency virus type 1 protease can provide an advantage for the emergence of the primary mutation D30N. We engineered protease mutants containing the active site mutation D30N alone and with the nonactive site polymorphisms M36I and/or A71V. 2003 Biochemistry Abstract HIV A71V;D30N;M36I 132;67;120 136;71;124 PR 14 22 14694110 Human immunodeficiency virus type 1 Tat regulates endothelial cell actin cytoskeletal dynamics through PAK1 activation and oxidant production. PAK1(K298A) blocked p47(phox) phosphorylation, and interference with NADPH oxidase function through superoxide scavenging or through expression of a transdominant inhibitor, p67(V204A), prevented GST-Tat-induced alterations in the actin cytoskeleton. 2004 Journal of virology Abstract HIV V204A 178 183 Tat 200 203 14694113 Role of the ectodomain of the gp41 transmembrane envelope protein of human immunodeficiency virus type 1 in late steps of the membrane fusion process. In contrast, three mutations in the loop region of the gp41 ectodomain, located on either side of the Cys-(X)(5)-Cys motif (W596 M and W610A) or at the distal end of HR1 (D589L), had limited or no apparent effect on membrane lipid mixing between Env(+) and target cells, while they blocked formation of syncytia and markedly reduced the exchanges of cytoplasmic fluorescent probes. 2004 Journal of virology Abstract HIV D589L;W596M;W610A 171;124;135 176;131;140 gp41;Env 55;246 59;249 14694113 Role of the ectodomain of the gp41 transmembrane envelope protein of human immunodeficiency virus type 1 in late steps of the membrane fusion process. The L568A mutation in the N-terminal heptad repeat (HR1) of gp41 resulted in parallel inhibition of the formation of syncytia and double-fluorescent cells, indicating that gp41 had a direct role in the exchange of fluorescent probes. 2004 Journal of virology Abstract HIV L568A 4 9 gp41;gp41 60;172 64;176 14694113 Role of the ectodomain of the gp41 transmembrane envelope protein of human immunodeficiency virus type 1 in late steps of the membrane fusion process. This finding confirmed that T20 can inhibit the late steps of membrane fusion (post-lipid mixing) and brought forth an indirect argument for the role of the gp41 loop region in these steps, as mutations conferring resistance to RPR103611V were mapped in this region (I595S or L602H). 2004 Journal of virology Abstract HIV I595S;L602H 267;276 273;281 gp41 157 161 14694133 Increased G-->A transition frequencies displayed by primer grip mutants of human immunodeficiency virus type 1 reverse transcriptase. A genetic screen based on the blue-white beta-galactosidase complementation assay designed to detect G-->A mutations arising during RNA-dependent DNA synthesis was used to compare the fidelity of mutant human immunodeficiency virus type 1 reverse transcriptases (RTs) with the mutations M230L and M230I with the wild-type enzyme, in the presence of biased deoxynucleoside triphosphate (dNTP) pools. 2004 Journal of virology Abstract HIV M230I;M230L 297;287 302;292 RT;RT 239;263 261;266 14694133 Increased G-->A transition frequencies displayed by primer grip mutants of human immunodeficiency virus type 1 reverse transcriptase. The mutant RTs with the M230L and M230I changes were found to be 20 to 70 times less faithful than the wild-type RT in the presence of low [dCTP]/[dTTP] ratios but showed similar fidelity in assays carried out with equimolar concentrations of each nucleotide. 2004 Journal of virology Abstract HIV M230I;M230L 34;24 39;29 RT;RT 11;113 14;115 14702153 Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. Primary mutations related to nelfinavir resistance (D30N and/or L90M) were observed in 43 (45%) of 96 nelfinavir-treated subjects. 2004 The Journal of infectious diseases Abstract HIV D30N;L90M 52;64 57;68 14722262 The membrane-proximal tyrosine-based sorting signal of human immunodeficiency virus type 1 gp41 is required for optimal viral infectivity. In spreading infections, including those using primary lymphocytes, the growth of the Y712A mutant was as impaired as Nef-negative virus, and the EnvY712A/Delta-Nef combination mutant was almost completely defective. 2004 Journal of virology Abstract HIV Y712A 86 91 Nef;Nef;Env 118;161;146 121;164;149 14723353 Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV-1 patients in Denmark. Resistance mutations in the RT-gene associated with NRTI-resistance were found in 1 patient, who was infected with zidovudine resistant HIV-1 harbouring the M41L mutation in combination with T215S and L210S. 2003 Scandinavian journal of infectious diseases Abstract HIV L210S;M41L;T215S 201;157;191 206;161;196 NRTI;RT 52;28 56;30 14723353 Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV-1 patients in Denmark. The T215S mutation has been showed to be associated with reversion of zidovudine resistance. 2003 Scandinavian journal of infectious diseases Abstract HIV T215S 4 9 14723353 Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV-1 patients in Denmark. The T215S mutation was found in 1 additional patient. 2003 Scandinavian journal of infectious diseases Abstract HIV T215S 4 9 14727218 Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. A full reversion of the Q151M mutation was observed in 5 of 5 patients who underwent treatment interruption after GRT. 2004 Clinical infectious diseases Abstract HIV Q151M 24 29 14727218 Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. Among 470 patients with acquired immune deficiency syndrome and/or human immunodeficiency virus infection (HIV/AIDS) who underwent genotype resistance testing (GRT) after the failure of therapy, 17 (3.6%) harbored the Q151M mutation. 2004 Clinical infectious diseases Abstract HIV Q151M 218 223 AIDS;AIDS 24;111 59;115 14727218 Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. By contrast, the Q151M mutation was inversely associated with lamivudine administration. 2004 Clinical infectious diseases Abstract HIV Q151M 17 22 14727218 Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. The Q151M mutation was associated with younger age, lower CD4(+) lymphocyte count, higher HIV RNA level, and treatment with >2 pre-GRT regimens. 2004 Clinical infectious diseases Abstract HIV Q151M 4 9 14741280 Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives. A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2004 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 164;170 169;175 14754429 A review of HIV-1 resistance to the nucleoside and nucleotide inhibitors. There are several major genetic mutational patterns of resistance and cross-resistance that evolve with the NRTIs including the thymidine analog mutations M41L, D67N, K70R, L210W, T215Y, and K219Q/E/W, the non-thymidine mutations M184V, L74V, and K65R, and the multidrug resistant Q151M complex, as well as others. 2003 Current drug targets. Infectious disorders Abstract HIV D67N;K219E;K219Q;K219W;K65R;K70R;L210W;L74V;M184V;M41L;Q151M;T215Y 161;191;191;191;247;167;173;237;230;155;281;180 165;200;200;200;251;171;178;241;235;159;286;185 NRTI 108 113 14757837 PCR amplification of DNA containing non-standard base pairs by variants of reverse transcriptase from Human Immunodeficiency Virus-1. A second mutation, E478Q, was introduced into the Y188L variant, in the event that the residual nuclease activity observed is due to the RT, and not a contaminant. 2004 Nucleic acids research Abstract HIV E478Q;Y188L 19;50 24;55 RT 137 139 14757837 PCR amplification of DNA containing non-standard base pairs by variants of reverse transcriptase from Human Immunodeficiency Virus-1. A variant of HIV-RT where Tyr 188 is replaced by Leu, has emerged from experiments where HIV was challenged to grow in the presence of drugs targeted against the RT, such as L-697639, TIBO and nevirapine. 2004 Nucleic acids research Abstract HIV Y188L 26 52 RT;RT 17;162 19;164 14759236 Effect of polymorphisms on the replicative capacity of protease inhibitor-resistant HIV-1 variants under drug pressure. Importantly, the polymorphic change L63P, although not conferring inhibitor resistance by itself, provided a significant replication benefit to both mutant viruses, particularly under drug pressure, and may reveal a far-reaching compensating power of polymorphic changes. 2004 Clinical microbiology and infection Abstract HIV L63P 36 40 14759236 Effect of polymorphisms on the replicative capacity of protease inhibitor-resistant HIV-1 variants under drug pressure. The role of drug pressure on the replicative capacity of protease inhibitor-resistant HIV-1 variants and the contribution of a common amino-acid polymorphism in the protease gene (L63P) to this process were investigated. 2004 Clinical microbiology and infection Abstract HIV L63P 180 184 PR;PR 57;165 65;173 14759236 Effect of polymorphisms on the replicative capacity of protease inhibitor-resistant HIV-1 variants under drug pressure. Using HIV-1 variants resistant to the protease inhibitors saquinavir (G48V/L90M) or indinavir (A71V/V82T/I84V), viral replication was studied in the presence or absence of inhibitor and a mutation at position 63. 2004 Clinical microbiology and infection Abstract HIV A71V;I84V;V82T;G48V;L90M 95;105;100;70;75 99;109;104;74;79 PR 38 46 14760883 Nucleoside and nucleotide analogue reverse transcriptase inhibitors: a clinical review of antiretroviral resistance. Resistance to multiple nucleoside reverse transcriptase inhibitors (NRTIs) may result from several genotypically distinct pathways, including the Q151M (151 complex), the 69 insertion complex, two distinct thymidine analogue mutational pathways and the K65R mutation. 2003 Antiviral therapy Abstract HIV K65R;Q151M 253;146 257;151 NRTI;NRTI 23;68 55;73 14761194 Computer-aided design, synthesis, and anti-HIV-1 activity in vitro of 2-alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-o nes as novel potent non-nucleoside reverse transcriptase inhibitors, also active against the Y181C variant. Interestingly, 2-cyclopentylamino-6-[1-(2,6-difluorophenyl)ethyl]-3,4-dihydro-5-methyl pyrimidin-4(3H)-one (9d) was active against the Y181C HIV-1 mutant strain at submicromolar concentration, with a resistance value similar to that of efavirenz, the last FDA-approved NNRTI for AIDS therapy, and 2-fold lower than that of its 2-cyclopentylthio counterpart 8d. 2004 Journal of medicinal chemistry Abstract HIV Y181C 135 140 NNRTI 269 274 AIDS 279 283 14761194 Computer-aided design, synthesis, and anti-HIV-1 activity in vitro of 2-alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-o nes as novel potent non-nucleoside reverse transcriptase inhibitors, also active against the Y181C variant. The introduction in 9d of a new anchor point (pyrimidine C-2 NH group), with the formation of a new hydrogen bond with Lys101, could compensate for the lack of positive hydrophobic ligand/NNBP interactions due to the Tyr181 to Cys181 mutation. 2004 Journal of medicinal chemistry Abstract HIV Y181C 217 233 14766818 Polymorphism and drug-selected mutations in the protease gene of human immunodeficiency virus type 2 from patients living in Southern France. In addition, at six positions (positions 7, 46, 62, 71, 90, and 99), the amino acid variability or the amino acid frequencies or both differed significantly in PI-treated and untreated patients, suggesting that mutations 7K-->R, 46V-->I, 62V-->A/T, 71V-->I, 90L-->M and 99L-->F were occurring under PI-selective pressure. 2004 Journal of clinical microbiology Abstract HIV L90M;V46I;V71I 258;229;249 265;236;256 PI;PI 160;299 162;301 14766874 Different viral rebound following discontinuation of antiretroviral therapy in cases of infection with viruses carrying L74V or thymidine-associated mutations. The greatest human immunodeficiency virus (HIV)-RNA rebounds were seen in 10 patients harboring an L74V mutation, and the presence of viruses with this mutation rapidly waned. 2004 Journal of clinical microbiology Abstract HIV L74V 99 103 14766874 Different viral rebound following discontinuation of antiretroviral therapy in cases of infection with viruses carrying L74V or thymidine-associated mutations. Thus, selection of an L74V mutation during didanosine therapy may compromise HIV replication in vivo. 2004 Journal of clinical microbiology Abstract HIV L74V 22 26 14769016 Crystal structure of the broadly cross-reactive HIV-1-neutralizing Fab X5 and fine mapping of its epitope. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. 2004 Biochemistry Abstract HIV Y100F 97 102 gp120 168 173 14963120 Genetic basis of hypersusceptibility to protease inhibitors and low replicative capacity of human immunodeficiency virus type 1 strains in primary infection. In chronically infected antiretrovirally treated patients, amprenavir HS has been associated with the mutation N88S in PR, but this mutation is not seen in untreated patients. 2004 Journal of virology Abstract HIV N88S 111 115 PR 119 121 14963138 Unselected mutations in the human immunodeficiency virus type 1 genome are mostly nonsynonymous and often deleterious. By applying the same system to an HIV-1 genome with a G262A mutation in the thumb region of the reverse transcriptase, a significant increase was observed in deletion and insertion mutation rates but no increase in the overall mutation rate in viral genomes was found. 2004 Journal of virology Abstract HIV G262A 54 59 RT 96 117 14963157 Assembly properties of the human immunodeficiency virus type 1 CA protein. One CA mutant (R18A) assembled into cylinders, cones, and spheres. 2004 Journal of virology Abstract HIV R18A 15 19 Capsid 4 6 14963157 Assembly properties of the human immunodeficiency virus type 1 CA protein. We suggest that these capsid shapes occur because the R18A mutation alters the frequency at which pentamers are incorporated into the hexagonal lattice. 2004 Journal of virology Abstract HIV R18A 54 58 Capsid 22 28 14971897 Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1. They were particularly potent against NNRTI-resistant viruses containing Y181C-, K103N-, and K103N-based double mutations, which account for a significant proportion of the clinical failure of the three currently marketed NNRTIs. 2004 Journal of medicinal chemistry Abstract HIV K103N;K103N;Y181C 81;93;73 86;98;78 NNRTI;NNRTI 38;222 43;228 14976601 Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. Response to tenofovir DF was reduced among patients with HIV-1 with >or=3 TAMs inclusive of either the M41L or L210W mutation (n=86) or patients who had a preexisting K65R mutation (n=6). 2004 The Journal of infectious diseases Abstract HIV K65R;L210W;M41L 167;111;103 171;116;107 14976601 Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. Slightly increased treatment responses were observed when the M184V mutation was present. 2004 The Journal of infectious diseases Abstract HIV M184V 62 67 14976604 A survival method to estimate the time to occurrence of mutations: an application to thymidine analogue mutations in HIV-1-infected patients. Although K70R has been described as the first mutation to appear in patients receiving ZDV monotherapy, the T215Y/F mutation appeared first in patients receiving dual-nucleoside combination therapy. 2004 The Journal of infectious diseases Abstract HIV K70R;T215F;T215Y 9;108;108 13;115;115 14980626 Synthesis of 6-arylvinyl analogues of the HIV drugs SJ-3366 and Emivirine. The most active compounds 1-ethoxymethyl, 1-(2-propynyloxymethyl), and 1-(2-methyl-3-phenylallyloxymethyl) substituted 6-[1-(3,5-dimethylphenyl)vinyl]-5-ethyl-1H-pyrimidine-2,4-dione (5b, 16, and 18) showed activities against HIV-1 wild type in the range of Efavirenz, and moderate activities against Y181C and Y181C+K103N mutant strains were also observed. 2004 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C;Y181C 317;301;311 322;306;316 14981751 Decrease of replicative capacity of HIV isolates after genotypic guided change of therapy. After the change of therapy, an increase in the number of drug resistance mutations in the protease gene was detected in both groups with a higher prevalence of M36I mutation in immune responders. 2004 Journal of medical virology Abstract HIV M36I 161 165 PR 91 99 14982794 Molecular mechanisms of tenofovir resistance conferred by human immunodeficiency virus type 1 reverse transcriptase containing a diserine insertion after residue 69 and multiple thymidine analog-associated mutations. A patient-derived HIV-1 strain (strain FS-SSS) that contained an insertion mutation in a background of additional resistance mutations M41L, L74V, L210W, and T215Y was obtained. 2004 Antimicrobial agents and chemotherapy Abstract HIV L210W;L74V;M41L;T215Y 147;141;135;158 152;145;139;163 14982794 Molecular mechanisms of tenofovir resistance conferred by human immunodeficiency virus type 1 reverse transcriptase containing a diserine insertion after residue 69 and multiple thymidine analog-associated mutations. In strain FS the insertion and T69S were reverted but the other resistance mutations were retained. 2004 Antimicrobial agents and chemotherapy Abstract HIV T69S 31 35 14990709 Unintegrated lentivirus DNA persistence and accessibility to expression in nondividing cells: analysis with class I integrase mutants. The FIV IN mutants (D66V and D66V/D118A) had class I properties: Gag/Pol precursor expression, proteolytic processing, particle formation, and reverse transcriptase (RT) production were normal, while the transduction of dividing fibroblasts was prevented and integration was blocked. 2004 Journal of virology Abstract HIV D118A;D66V;D66V 34;20;29 39;25;33 RT;Pol;Gag;IN;RT 143;69;65;8;166 164;72;68;10;168 14990731 Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. The active-site expansion includes position 82 and 84 mutations due to the alterations in the amino acid side chains from longer to shorter (e.g., V82A and I84V). 2004 Journal of virology Abstract HIV I84V;V82A 156;147 160;151 14999613 Detection of drug-resistant minority variants of HIV-1 during virologic failure of indinavir, lamivudine, and zidovudine. One had evidence of V82A in 9 of 30 clones at week 24, with no increase at week 40. 2004 The Journal of infectious diseases Abstract HIV V82A 20 24 14999613 Detection of drug-resistant minority variants of HIV-1 during virologic failure of indinavir, lamivudine, and zidovudine. The dominant week-40 82V-M184V clones had changes at protease codons 62-64, compared with all clones at week 24 and minority clones at week 40. 2004 The Journal of infectious diseases Abstract HIV M184V 25 30 PR 53 61 15000558 The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection. Only the V118I RT mutation was statistically more common among virologic failing than non-failing NRTI pretreated patients (p < 0.05). 2004 Scandinavian journal of infectious diseases Abstract HIV V118I 9 14 NRTI;RT 98;15 102;17 15000558 The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection. Stepwise multiple regression analysis for viral failure resulted in a model with only the V118I RT mutation entering the model (p < 0.01). 2004 Scandinavian journal of infectious diseases Abstract HIV V118I 90 95 RT 96 98 15000558 The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection. The viral strains from the virologic failing patients harboured 3-6 reverse transcriptase (RT) mutations, including the V118I mutation in 5/6 cases prior to PI-ART or at viral rebound. 2004 Scandinavian journal of infectious diseases Abstract HIV V118I 120 125 RT;PI;RT 68;157;91 89;159;93 15000581 HIV fitness and resistance as covariates associated with the appearance of mutations under antiretroviral treatment. A deep molecular analysis (90 clones) conducted on proviral DNA of lymphocytes demonstrates that M184V strains are no longer detected in plasma and proviral DNA shortly after interruption of therapeutic regimens including lamivudine (even if a new therapeutic regimen has been started). 2003 Scandinavian journal of infectious diseases. Supplementum Abstract HIV M184V 97 102 15000581 HIV fitness and resistance as covariates associated with the appearance of mutations under antiretroviral treatment. At the time of interruption of specific viral pressure (lamivudine in the case of M184V), wild-type virus easily overgrows mutated strains. 2003 Scandinavian journal of infectious diseases. Supplementum Abstract HIV M184V 82 87 15000581 HIV fitness and resistance as covariates associated with the appearance of mutations under antiretroviral treatment. In the case of M184V (a mutation involving the catalytic site of HIV reverse transcriptase), no pathways of viral escape have been defined so far; it is thus conceivable that the mutated virus maintains a relatively low replicative capacity. 2003 Scandinavian journal of infectious diseases. Supplementum Abstract HIV M184V 15 20 RT 69 90 15000581 HIV fitness and resistance as covariates associated with the appearance of mutations under antiretroviral treatment. This supports the concept that the low fitness of M184V strains is not easily compensated by additional mutations. 2003 Scandinavian journal of infectious diseases. Supplementum Abstract HIV M184V 50 55 15008125 Protease mutations in HIV-1 non-B strains infecting drug-naive villagers in Cameroon. Secondary PI resistance-associated mutations were identified at five sites: L10I/V (16%), K20R (8%), M36I (98%), L63P (13%), and V77I (6%). 2004 AIDS research and human retroviruses Abstract HIV K20R;L10I;L10V;L63P;M36I;V77I 90;76;76;113;101;129 94;82;82;117;105;133 PI 10 12 15013042 Conflicting interpretations of the prevalence of mutations associated with drug resistance in antiviral naive HIV-1 patients with acute and chronic infection. In particular, three patients (4.8%) carried viral major mutations (T69D and M41L) associated with resistance to reverse transcriptase inhibitors, whereas only one showed the presence of M46L, which is correlated with partial resistance to some protease inhibitors. 2004 International journal of antimicrobial agents Abstract HIV M41L;M46L;T69D 77;187;68 81;191;73 RT;PR 113;245 134;253 15016842 Azido-containing diketo acid derivatives inhibit human immunodeficiency virus type 1 integrase in vivo and influence the frequency of deletions at two-long-terminal-repeat-circle junctions. Inhibition of HIV-1 IN in vivo was demonstrated by the observation that previously described L-708,906 resistance mutations in HIV-1 IN (T66I and T66I/S153Y) also conferred resistance to the azido-group-containing DKAs. 2004 Journal of virology Abstract HIV S153Y;T66I;T66I 151;137;146 156;142;150 IN;IN 20;133 22;135 15018707 Mutations conferring drug resistance affect eukaryotic expression of HIV type 1 reverse transcriptase. Genes encoding AZT-resistant RTs with single or combined mutations D67N, K70R, T215F, and K219Q, and RTs derived from drug-resistant HIV-1 strains were designed and expressed in a variety of eukaryotic cells. 2004 AIDS research and human retroviruses Abstract HIV D67N;K219Q;K70R;T215F 67;90;73;79 71;95;77;84 RT;RT 29;101 32;104 15026203 Investigating the effects of stereochemistry on incorporation and removal of 5-fluorocytidine analogs by mitochondrial DNA polymerase gamma: comparison of D- and L-D4FC-TP. While these results suggest that D-D4FC may present more mitochondrial toxicity than L-D4FC in cell-free assays, we have previously shown that HIV-1 RT prefers D-D4FC-TP as a substrate over the L-isomer, particularly in the case of mutant forms of RT associated with nucleoside drug resistance such as M184V. 2004 Antiviral research Abstract HIV M184V 302 307 RT;RT 149;248 151;250 15027854 Synthesis, structure-activity relationships, and mechanism of drug resistance of D- and L-beta-3'-fluoro-2',3'-unsaturated-4'-thionucleosides as anti-HIV agents. However, L-3'F-4'Sd4C 34 and L-3'F-4'Sd4FC 35 showed high cross-resistance to 3TC-resistant mutant (M184V) RT. 2004 Journal of medicinal chemistry Abstract HIV M184V 100 105 RT 107 109 15027854 Synthesis, structure-activity relationships, and mechanism of drug resistance of D- and L-beta-3'-fluoro-2',3'-unsaturated-4'-thionucleosides as anti-HIV agents. Like other unnatural L-nucleosides, the unfavorable steric hindrance of the sugar moiety of L-3'F-4'Sd4CTP with the side chain of Val184 explains its significant cross-resistance to the M184V mutant. 2004 Journal of medicinal chemistry Abstract HIV M184V 186 191 15031792 Synonymous genetic polymorphisms within Brazilian human immunodeficiency virus Type 1 subtypes may influence mutational routes to drug resistance. An inverse relationship between the L210W and K70R mutations was also observed. 2004 The Journal of infectious diseases Abstract HIV K70R;L210W 46;36 50;41 15031792 Synonymous genetic polymorphisms within Brazilian human immunodeficiency virus Type 1 subtypes may influence mutational routes to drug resistance. The clinical significance of position 210 was confirmed within a large Brazilian database, in which we identified a lower prevalence of the L210W mutation in subtype F1 virus, compared with subtype B virus, in patients matched for thymidine-analogue experience. 2004 The Journal of infectious diseases Abstract HIV L210W 140 145 15040544 Strategies to decrease viral load rebound, and prevent loss of CD4 and onset of resistance during structured treatment interruptions. A relevant mutation in the reverse transcriptase sequence (K70R) emerged in one patient interrupting treatment after 36 weeks of continuous therapy and in one patient after four STI cycles. 2004 Antiviral therapy Abstract HIV K70R 59 63 RT 27 48 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. Consistent with this result, purified HIV-1 RT carrying K65R RT or K65R/L74V substitutions exhibits an 8-fold resistance to ddATP as judged by pre-steady state kinetics of incorporation of a single nucleotide into DNA. 2004 The Journal of biological chemistry Abstract HIV K65R;K65R;L74V 56;67;72 60;71;76 RT;RT 44;61 46;63 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. Here we show that recombinant viruses carrying K65R and K65R/L74V display the same resistance level to ddI (about 9.5-fold) relative to wild type. 2004 The Journal of biological chemistry Abstract HIV K65R;K65R;L74V 47;56;61 51;60;65 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. However, the K65R/L74V virus replication capacity is severely impaired relative to that of wild-type virus. 2004 The Journal of biological chemistry Abstract HIV K65R;L74V 13;18 17;22 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. Human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) K65R or L74V substitutions confer viral resistance to 2',3'-dideoxyinosine (ddI) in vivo. 2004 The Journal of biological chemistry Abstract HIV K65R;L74V 68;78 74;82 RT;RT 37;66 58;68 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. Resistance is due to a selective decrease of the catalytic rate constant k(pol): 22-fold (from 7.2 to 0.33 s(-1)) for K65R RT and 84-fold (from 7.2 to 0.086 s(-1)) for K65R/L74V RT. 2004 The Journal of biological chemistry Abstract HIV K65R;K65R;L74V 118;168;173 122;172;177 Pol;RT;RT 75;123;178 78;125;180 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. The order of incorporation efficiency is wild-type RT > L74V RT > K65R RT > K65R/L74V RT. 2004 The Journal of biological chemistry Abstract HIV K65R;K65R;L74V;L74V 66;76;81;56 70;80;85;60 RT;RT;RT;RT 51;61;71;86 53;63;73;88 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. The two substitutions never occur together, and L74V is frequently found in patients receiving ddI, while K65R is not. 2004 The Journal of biological chemistry Abstract HIV K65R;L74V 106;48 110;52 15044478 A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. This loss of viral fitness is correlated to a poor ability of K65R/L74V RT to use natural nucleotides relative to wild-type RT: 15% that of wild-type RT for dATP, 36% for dGTP, 50% for dTTP, and 25% for dCTP. 2004 The Journal of biological chemistry Abstract HIV K65R;L74V 62;67 66;71 RT;RT;RT 72;124;150 74;126;152 15044738 HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: possible contributions to drug resistance and a potential new target site for drugs. Consequently, this study examined structural properties sampled during 22 nsec, all atom molecular dynamics (MD) simulations (in explicit water) of both a wild-type and the drug-resistant V82F/I84V mutant of HIV-1 protease. 2004 Protein science Abstract HIV I84V;V82F 193;188 197;192 PR 214 222 15044738 HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: possible contributions to drug resistance and a potential new target site for drugs. The V82F/I84V mutation significantly decreases the binding affinity of all HIV-1 protease inhibitors currently used clinically. 2004 Protein science Abstract HIV I84V;V82F 9;4 13;8 PR 81 89 15047556 Human immunodeficiency virus type 1 reverse transcriptase mutation selection during in vitro exposure to tenofovir alone or combined with abacavir or lamivudine. In the wild-type virus, TFV-ABC and TFV-3TC selected K65R (with reduced susceptibility to all three inhibitors) and then Y115F. 2004 Antimicrobial agents and chemotherapy Abstract HIV K65R;Y115F 53;121 57;126 15047556 Human immunodeficiency virus type 1 reverse transcriptase mutation selection during in vitro exposure to tenofovir alone or combined with abacavir or lamivudine. TFV-containing regimens might increase K65R selection, which confers multiple nucleoside reverse transcriptase inhibitor resistance. 2004 Antimicrobial agents and chemotherapy Abstract HIV K65R 39 43 NRTI 78 110 15047690 Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA primers. Insertions are usually associated with thymidine analogue resistance mutations, such as T215Y. 2004 The Journal of biological chemistry Abstract HIV T215Y 88 93 15047690 Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA primers. The mutation D67N, which is rarely found in insertion-containing strains, had no effect on excision and a minor influence on resistance. 2004 The Journal of biological chemistry Abstract HIV D67N 13 17 15047690 Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA primers. The presence of both the insertion and mutation T215Y in the wild-type BH10 RT conferred significant ATP-mediated removal activity and moderate resistance to AZT. 2004 The Journal of biological chemistry Abstract HIV T215Y 48 53 RT 76 78 15051383 Replication-dependent 65R-->K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V. Although several nucleoside reverse transcriptase inhibitors select RT mutations K65R and L74V, the combination of 65R + 74V is rare in clinics. 2004 Virology Abstract HIV K65R;L74V 81;90 85;94 NRTI;RT 17;68 49;70 15051383 Replication-dependent 65R-->K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V. Replication kinetic assays revealed that the mutant K65R + L74V is unstable, and 65R-->K reversion occurs during replication of virus in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBM) cells in the absence of selection pressure. 2004 Virology Abstract HIV K65R;L74V 52;59 56;63 15051383 Replication-dependent 65R-->K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V. To analyze the impact of these RT mutations on viral replication, a double mutant containing K65R + L74V was created by site-directed mutagenesis in a pNL4-3 background. 2004 Virology Abstract HIV K65R;L74V 93;100 97;104 RT 31 33 15056001 A phenylnorstatine inhibitor binding to HIV-1 protease: geometry, protonation, and subsite-pocket interactions analyzed at atomic resolution. A structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses. 2004 Journal of medicinal chemistry Abstract HIV V82A 69 77 PR 60 68 15060438 Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C. CONCLUSION: Collectively, these data indicate that genetic variation at NNRTI resistance-associated positions such as V106M and A98S is substantially greater in subtype C-infected patients than in subtype B-infected patients. 2004 AIDS (London, England) Abstract HIV A98S;V106M 128;118 132;123 NNRTI 72 77 15060438 Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C. In NNRTI experienced patients, the number of A98G/S changes was significantly higher in subtype C patients treated with either efavirenz or nevirapine (P < 0.0001), and V106M was higher in efavirenz-treated subtype C-infected patients (P < 0.0001). 2004 AIDS (London, England) Abstract HIV A98G;A98S;V106M 45;45;169 51;51;174 NNRTI 3 8 15060438 Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C. The frequency of nucleoside associated mutations, but not M184V, in treated patients was significantly higher in subgroup B-infected patients (P = 0.028). 2004 AIDS (London, England) Abstract HIV M184V 58 63 15063112 Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis. The amounts of viral DNA synthesized decreased in 3TC-treated cells when the cells were infected with wild-type virus and the M184A mutant. 2004 Virology Abstract HIV M184A 126 131 15063112 Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis. The M184T mutation increased the proportion of 2-LTR circle junctions containing a tRNA insertion, suggesting that the mutation affected the RNase H activity of RT. 2004 Virology Abstract HIV M184T 4 9 LTR;RT 49;161 52;163 15063744 HIV-1 auxiliary regulatory protein Vpr promotes ubiquitination and turnover of Vpr mutants containing the L64P mutation. Co-expression of the wild type Vpr with the VprW54A/L64P mutant resulted in normal synthesis of the mutant mRNA but enhanced ubiquitination and turnover of the mutant protein. 2004 FEBS letters Abstract HIV L64P 52 56 Vpr;Vpr 31;44 34;47 15063744 HIV-1 auxiliary regulatory protein Vpr promotes ubiquitination and turnover of Vpr mutants containing the L64P mutation. In this report, experimental evidence suggests a novel biological activity of Vpr: facilitation of the turnover of Vpr mutants bearing the L64P mutation. 2004 FEBS letters Abstract HIV L64P 139 143 Vpr;Vpr 78;115 81;118 15066177 Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site. PR(V82A) showed local changes in residues 81-82 at the site of the mutation, while PR(L90M) showed local changes near Met90 and an additional interaction with indinavir. 2004 European journal of biochemistry Abstract HIV L90M;V82A 86;3 90;7 PR;PR 0;83 2;85 15066177 Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site. The crystal structures of the wild-type HIV-1 protease (PR) and the two resistant variants, PR(V82A) and PR(L90M), have been determined in complex with the antiviral drug, indinavir, to gain insight into the molecular basis of drug resistance. 2004 European journal of biochemistry Abstract HIV L90M;V82A 108;95 112;99 PR;PR;PR;PR 46;56;92;105 54;58;94;107 15066177 Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site. The inhibition (K(i)) of PR(V82A) and PR(L90M) was 3.3- and 0.16-fold, respectively, relative to the value for PR. 2004 European journal of biochemistry Abstract HIV L90M;V82A 41;28 45;32 PR;PR;PR 25;38;111 27;40;113 15066177 Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site. V82A and L90M correspond to an active site mutation and nonactive site mutation, respectively. 2004 European journal of biochemistry Abstract HIV L90M;V82A 9;0 13;4 15066436 High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. Finally, the 1.10A resolution structure of PR(V82A) with UIC-94017 showed an unusual distribution of electron density for the catalytic aspartate residues, which is discussed in relation to the reaction mechanism. 2004 Journal of molecular biology Abstract HIV V82A 46 50 PR 43 45 15066436 High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. PR(V82A) showed differences in the position of the main-chain atoms of residue 82 compared to PR structure that better accommodated the inhibitor. 2004 Journal of molecular biology Abstract HIV V82A 3 7 PR;PR 0;94 2;96 15066436 High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. The crystal structures of PR and PR(I84V) with UIC-94017 ternary complexes show that the inhibitor binds to the protease in two overlapping positions, while the PR(V82A) complex had one ordered inhibitor. 2004 Journal of molecular biology Abstract HIV I84V;V82A 36;164 40;168 PR;PR;PR;PR 112;26;33;161 120;28;35;163 15066436 High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. We have determined the high-resolution crystal structures of UIC-94017 in complexes with wild-type HIV-1 protease (PR) and mutant proteases PR(V82A) and PR(I84V) that are common in drug-resistant HIV. 2004 Journal of molecular biology Abstract HIV I84V;V82A 156;143 160;147 PR;PR;PR;PR;PR 105;130;115;140;153 113;139;117;142;155 15067030 Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. 2004 The Journal of experimental medicine Abstract HIV A146P 4 9 15072756 HIV protease mutations associated with amprenavir resistance during salvage therapy: importance of I54M. Among mutations newly detected after amprenavir treatment, I54M occurred in six cases, I54L in two cases, M46I in two cases, I47V in one case and I50V in one case. 2004 Journal of clinical virology Abstract HIV I47V;I50V;I54L;I54M;M46I 125;146;87;59;106 129;150;91;63;110 15072756 HIV protease mutations associated with amprenavir resistance during salvage therapy: importance of I54M. CONCLUSIONS: Protease I54M frequently appears after amprenavir therapy, and when combined with pre-existing mutations, leads to high-level amprenavir resistance and treatment failure. 2004 Journal of clinical virology Abstract HIV I54M 22 26 PR 13 21 15072756 HIV protease mutations associated with amprenavir resistance during salvage therapy: importance of I54M. HIV protease mutations associated with amprenavir resistance included I84V, I50V, I47V, V32I, and I54M. 2004 Journal of clinical virology Abstract HIV I47V;I50V;I54M;I84V;V32I 82;76;98;70;88 86;80;102;74;92 PR 4 12 15072756 HIV protease mutations associated with amprenavir resistance during salvage therapy: importance of I54M. When compared with pretreatment plasma without the mutation, recombinant phenotyping showed that I54M increased the amprenavir resistance by at least 6-fold, resulting in up to 48-fold resistance over a drug-sensitive control. 2004 Journal of clinical virology Abstract HIV I54M 97 101 15073682 Lack of evidence for protease evolution in HIV-1-infected patients after 2 years of successful highly active antiretroviral therapy. Only 1 of 271 individual protease clones showed a major resistance substitution (M46I [patient D]). 2004 The Journal of infectious diseases Abstract HIV M46I 81 86 PR 25 33 15078095 A role for dNTP binding of human immunodeficiency virus type 1 reverse transcriptase in viral mutagenesis. Rather, the V148I and Q151N mutations alter RT fidelity by weakening the ability of the polymerase to complete mismatch extension, the second step of mutation synthesis. 2004 Biochemistry Abstract HIV Q151N;V148I 22;12 27;17 Pol;RT 88;44 98;46 15078095 A role for dNTP binding of human immunodeficiency virus type 1 reverse transcriptase in viral mutagenesis. These differences in binding and catalysis translate into 24- and 15.9-fold increase in mismatch extension fidelity for the V148I and Q151N RT mutants, respectively. 2004 Biochemistry Abstract HIV Q151N;V148I 134;124 139;129 RT 140 142 15078095 A role for dNTP binding of human immunodeficiency virus type 1 reverse transcriptase in viral mutagenesis. We found that the V148I and Q151N mutant viruses had 3.8- and 5.7-fold higher fidelities than wild-type viruses, respectively, indicating that the molecular interaction between HIV-1 RT and the dNTP substrate contributes to viral mutagenesis. 2004 Biochemistry Abstract HIV Q151N;V148I 28;18 33;23 RT 183 185 15078095 A role for dNTP binding of human immunodeficiency virus type 1 reverse transcriptase in viral mutagenesis. When we introduce either a V148I or Q151N mutation, RT fidelity increases 8.7- or 13-fold, respectively, as measured by the M13 lacZalpha forward mutation assay. 2004 Biochemistry Abstract HIV Q151N;V148I 36;27 41;32 RT 52 54 15078945 Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). In the absence of drug, these mutants displayed reduced fitness compared to wild-type virus with a relative order of fitness of wild type > I37T > V38 M > D36S/V38 M; this order was reversed in the presence of ENF. 2004 Journal of virology Abstract HIV D36S;D36V;I37T;V38M;V38M 155;155;140;160;147 159;159;144;165;152 15078945 Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). Likewise, recombinant viruses carrying ENF resistance mutations selected in vivo displayed reduced fitness in the absence of ENF with a relative order of wild type > N42T > V38A > N42T/N43K approximately N42T/N43S > V38A/N42D approximately V38A/N42T. 2004 Journal of virology Abstract HIV N42D;N42T;N42T;N42T;N42T;N43K;N43S;V38A;V38A;V38A 221;245;166;180;204;185;209;173;216;240 225;249;170;184;208;189;213;177;220;244 15084137 Structural and energetic analyses of the effects of the K103N mutation of HIV-1 reverse transcriptase on efavirenz analogues. The effect of the K103N mutation of HIV-1 reverse transcriptase (RT) on the activity of efavirenz analogues was studied via Monte Carlo/free energy perturbation calculations. 2004 Journal of medicinal chemistry Abstract HIV K103N 18 23 RT;RT 42;65 63;67 15084137 Structural and energetic analyses of the effects of the K103N mutation of HIV-1 reverse transcriptase on efavirenz analogues. The relative fold resistance energies indicate that efavirenz binds to K103N RT in a manner similar to the wild-type enzyme. 2004 Journal of medicinal chemistry Abstract HIV K103N 71 76 RT 77 79 15090770 GW433908/ritonavir once daily in antiretroviral therapy-naive HIV-infected patients: absence of protease resistance at 48 weeks. In the nelfinavir arm the key protease mutations D30N and/or L90M were frequently observed. 2004 AIDS (London, England) Abstract HIV D30N;L90M 49;61 53;65 PR 30 38 15095972 Crystal structures of HIV-1 reverse transcriptases mutated at codons 100, 106 and 108 and mechanisms of resistance to non-nucleoside inhibitors. Leu100Ile, Val106Ala and Val108Ile are mutations in HIV-1 reverse transcriptase (RT) that are observed in the clinic and give rise to resistance to certain non-nucleoside inhibitors (NNRTIs) including the first-generation drug nevirapine. 2004 Journal of molecular biology Abstract HIV L100I;V106A;V108I 0;11;25 9;20;34 RT;NNRTI;RT 58;183;81 79;189;83 15095972 Crystal structures of HIV-1 reverse transcriptases mutated at codons 100, 106 and 108 and mechanisms of resistance to non-nucleoside inhibitors. Shifts in side-chain and inhibitor positions compared to wild-type RT are observed in complexes of nevirapine and the second-generation NNRTI UC-781 with RT(Leu100Ile) and RT(Val106Ala), leading to perturbations in inhibitor contacts with Tyr181 and Tyr188. 2004 Journal of molecular biology Abstract HIV L100I;R100I;R106A;T100I;T106A;V106A 157;157;175;157;175;175 166;166;184;166;184;184 NNRTI;RT;RT;RT 136;67;154;172 141;69;156;174 15095972 Crystal structures of HIV-1 reverse transcriptases mutated at codons 100, 106 and 108 and mechanisms of resistance to non-nucleoside inhibitors. Thus in contrast to most NNRTI resistance mutations RT(Val108Ile) appears to act via an indirect mechanism which in this case is through alterations of the ring stacking interactions of the drug particularly with Tyr181. 2004 Journal of molecular biology Abstract HIV R108I;T108I;V108I 55;55;55 64;64;64 NNRTI;RT 25;52 30;54 15095972 Crystal structures of HIV-1 reverse transcriptases mutated at codons 100, 106 and 108 and mechanisms of resistance to non-nucleoside inhibitors. Val108 does not have direct contact with nevirapine in wild-type RT and in the RT(Val108Ile) complex the biggest change observed is at the distally positioned Tyr181 which is > 8 A from the mutation site. 2004 Journal of molecular biology Abstract HIV R108I;T108I;V108I 82;82;82 91;91;91 RT;RT 65;79 67;81 15097148 Comparison of drug resistance mutations and their interpretation in patients infected with non-B HIV-1 variants and matched patients infected with HIV-1 subtype B. In the protease gene, differences between patients infected with B or non-B strains were mainly observed for mutations playing a minor role in drug resistance and known to occur mainly as a natural polymorphism in non-B strains: K20R/M/I, M36I, L63P, A71V/T, and V77I. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A71T;A71V;K20I;K20M;K20R;L63P;M36I;V77I 251;251;229;229;229;245;239;263 257;257;237;237;237;249;243;267 PR 7 15 15097148 Comparison of drug resistance mutations and their interpretation in patients infected with non-B HIV-1 variants and matched patients infected with HIV-1 subtype B. RESULTS: RT mutations M41L, L210W, and, to a lesser extent, T215Y were less prevalent in patients infected with non-B variants. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L210W;M41L;T215Y 28;22;60 33;26;65 RT 9 11 15097303 Rate of thymidine analogue resistance mutation accumulation with zidovudine- or stavudine-based regimens. The frequency of K70R and T215Y or F mutations was similar in both groups, although M41L was observed more frequently in samples from ZDV-treated subjects. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M41L;T215Y 17;84;26 21;88;31 15103623 A structural and thermodynamic escape mechanism from a drug resistant mutation of the HIV-1 protease. The structures of the two compounds bound to the wild type and V82F/I84V HIV-1 protease have been determined by X-ray crystallography at 2.0 A resolution. 2004 Proteins Abstract HIV I84V;V82F 68;63 72;67 PR 79 87 15103623 A structural and thermodynamic escape mechanism from a drug resistant mutation of the HIV-1 protease. The V82F/I84V double mutation is located within the binding site cavity and affects all protease inhibitors in clinical use. 2004 Proteins Abstract HIV I84V;V82F 9;4 13;8 PR 88 96 15105107 Effects of drug resistance mutations L100I and V106A on the binding of pyrrolobenzoxazepinone nonnucleoside inhibitors to the human immunodeficiency virus type 1 reverse transcriptase catalytic complex. In order to better understand the structural basis for this selectivity, we exploited some PBO analogs characterized by various substituents at C-3 and by different inhibition potencies and drug resistance profiles, and we studied their interaction with HIV-1 RT wild type or carrying the drug resistance mutations L100I and V106A. 2004 Antimicrobial agents and chemotherapy Abstract HIV L100I;V106A 315;325 320;330 RT 260 262 15105107 Effects of drug resistance mutations L100I and V106A on the binding of pyrrolobenzoxazepinone nonnucleoside inhibitors to the human immunodeficiency virus type 1 reverse transcriptase catalytic complex. The V106A mutation conferred resistance to PBO 354 by increasing its dissociation rate from the enzyme, whereas the L100I mutation mainly decreased the association rate. 2004 Antimicrobial agents and chemotherapy Abstract HIV L100I;V106A 116;4 121;9 15113844 Blocking of human immunodeficiency virus type-1 virion autolysis by autologous p2(gag) peptide. In this study, Ala substitutions (Met4Ala and Thr8Ala) and deletion of amino acid Asn9 within the nona p2(gag) peptide (AEAMSQVTN) were found to decrease the inhibitory effect on HIV-1 PR activity. 2004 Journal of biochemistry Abstract HIV M4A;T8A 34;46 42;53 Gag;PR 106;185 109;187 15113886 Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. However, early reverse-transcribed DNA products were absent in the lysate of cells infected with the C130S mutant virus, indicating that the mutation abolished the ability of the virus to initiate endogenous reverse transcription. 2004 Journal of virology Abstract HIV C130S 101 106 RT 208 229 15113886 Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. The C130S substitution within the core region may disrupt the protein recognition interface of the C-terminal domain and abolish its ability to interact with RT. 2004 Journal of virology Abstract HIV C130S 4 9 RT 158 160 15113886 Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. When introduced into the NL4-3 molecular clone of HIV-1, mutant viruses encoding Cys mutations at positions 56 and 65 of integrase replicated similarly to the wild-type virus in CD4(+)-T-cell lines, whereas the C130S-containing virus was noninfectious. 2004 Journal of virology Abstract HIV C130S 211 216 IN 121 130 15113887 Interaction between human immunodeficiency virus type 1 reverse transcriptase and integrase proteins. An oligomerization-defective mutant of IN, V260E, retained the ability to bind to RT, showing that IN oligomerization may not be required for interaction. 2004 Journal of virology Abstract HIV V260E 43 48 IN;IN;RT 39;99;82 41;101;84 15113918 Characterization of a subtype D human immunodeficiency virus type 1 isolate that was obtained from an untreated individual and that is highly resistant to nonnucleoside reverse transcriptase inhibitors. D14-UG did not contain the classic amino acid substitutions conferring NNRTI resistance (e.g., Y181C, K103N, and G190A) but did have some putative sites associated with drug resistance, I135L, T139V, and V245T. 2004 Journal of virology Abstract HIV G190A;I135L;K103N;T139V;V245T;Y181C 113;186;102;193;204;95 118;191;107;198;209;100 NNRTI 71 76 15113918 Characterization of a subtype D human immunodeficiency virus type 1 isolate that was obtained from an untreated individual and that is highly resistant to nonnucleoside reverse transcriptase inhibitors. The results showed that I135L and/or V245T mutations can confer high-level resistance to nevirapine and delavirdine as well as low level cross-resistance to efavirenz. 2004 Journal of virology Abstract HIV I135L;V245T 24;37 29;42 15116307 Mutations in HIV-1 reverse transcriptase potentially associated with hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors: effect on response to efavirenz-based therapy in an urban observational cohort. CONCLUSIONS: The M41L, M184V, L210W, and T215Y mutations were associated with a better, although transient, virological outcome in patients treated with efavirenz-based regimens. 2004 The Journal of infectious diseases Abstract HIV L210W;M184V;M41L;T215Y 30;23;17;41 35;28;21;46 15116307 Mutations in HIV-1 reverse transcriptase potentially associated with hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors: effect on response to efavirenz-based therapy in an urban observational cohort. RESULTS: The baseline RT mutations M41L, M184V, L210W, and T215Y and the M41L/T215Y and M41L/T215Y/M184V combinations were associated with virological suppression for efavirenz-treated patients, whereas, for PI-treated patients, only the M184V mutation was associated with virological suppression, and the L210W mutation showed a negative correlation; no correlation was found between any mutation and virological response without rebound. 2004 The Journal of infectious diseases Abstract HIV M184V;M41L;T215Y;L210W;L210W;M184V;M184V;M41L;M41L;T215Y;T215Y 99;88;93;48;306;41;238;35;73;59;78 104;92;98;53;311;46;243;39;77;64;83 PI;RT 208;22 210;24 15122516 Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. Clinical isolates obtained from PI-naive patients designated as experiencing virologic failure while receiving ATV-containing regimens contained a unique isoleucine-to-leucine substitution at amino acid residue 50 (I50L) of the HIV-1 protease. 2004 The Journal of infectious diseases Abstract HIV I50L;I50L 215;154 219;213 PR;PI 234;32 242;34 15122516 Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. Comparison of viruses bearing I50L with those bearing I50V revealed specific resistance to ATV and amprenavir, respectively, with no evidence of cross-resistance. 2004 The Journal of infectious diseases Abstract HIV I50L;I50V 30;54 34;58 15122516 Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. The I50L substitution, observed in all isolates exhibiting phenotypic resistance to ATV, emerged in a variety of different backgrounds and was most frequently accompanied by A71V, K45R, and/or G73S. 2004 The Journal of infectious diseases Abstract HIV A71V;G73S;I50L;K45R 174;193;4;180 178;197;8;184 15122516 Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. The unique I50L substitution is the signature mutation for resistance to ATV. 2004 The Journal of infectious diseases Abstract HIV I50L 11 15 15122516 Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. Viruses containing an I50L substitution were growth impaired, displayed ATV-specific resistance, and had increased susceptibilities (His mutation modifies drastically the structure of the core domain (residues 12 to 53) of NCp7, His28(12-53)NCp7 still interacts with a 10-fold-lower affinity to specific nucleic acid targets, such as SL3, a stem-loop critically involved in viral RNA packaging, and without affinity change with the nonspecific, single-stranded nucleic acid poly(T). 2004 Journal of virology Abstract HIV C28H 13 24 NC;NC 111;129 113;131 15166526 Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection. The vpr R77Q change was recognized in seven patients. 2004 AIDS (London, England) Abstract HIV R77Q 8 12 Vpr 4 7 15168738 K65R, TAMs and tenofovir. Among treatment-naive patients who developed the K65R mutation in clinical trials, successful second line regimens were established. 2004 AIDS reviews Abstract HIV K65R 49 53 15168738 K65R, TAMs and tenofovir. Based on clinical cut-offs established for the individual NRTIs, the phenotypic results with K65R suggest full-to-partial drug activity for multiple NRTIs, including tenofovir, against the K65R mutant. 2004 AIDS reviews Abstract HIV K65R;K65R 93;189 97;193 NRTI;NRTI 58;149 63;154 15168738 K65R, TAMs and tenofovir. From cross-sectional genotypic analyses, the K65R mutation and TAMs appear to represent separate patterns of NRTI resistance. 2004 AIDS reviews Abstract HIV K65R 45 49 NRTI 109 113 15168738 K65R, TAMs and tenofovir. From in vitro phenotypic analysis, the K65R mutation shows no cross-resistance to zidovudine, but low-level resistance to tenofovir and the other NRTIs. 2004 AIDS reviews Abstract HIV K65R 39 43 NRTI 146 151 15168738 K65R, TAMs and tenofovir. Similar to the M184V mutation, the K65R mutation is also associated with reduced in vitro viral replication capacity, hallmarks of which can be demonstrated at the enzymatic level. 2004 AIDS reviews Abstract HIV K65R;M184V 35;15 39;20 15168738 K65R, TAMs and tenofovir. The K65R mutation can result from tenofovir DF, abacavir, stavudine, zalcitabine or didanosine therapy. 2004 AIDS reviews Abstract HIV K65R 4 8 15168738 K65R, TAMs and tenofovir. The response to tenofovir disoproxil fumarate (TDF) therapy is also limited by certain patterns of TAMs (> or = 3 TAMs with M41L or L210W). 2004 AIDS reviews Abstract HIV L210W;M41L 132;124 137;128 15168738 K65R, TAMs and tenofovir. Thus, the K65R mutation appears manageable for the sequencing of treatment regimens in the case of its development. 2004 AIDS reviews Abstract HIV K65R 10 14 15168798 Persistence of mutations during replication of an HIV library containing combinations of selected protease mutations. By contrast, the half lives (t(1/2)) of the D30N and N88D mutations associated with nelfinavir (NFV) resistance were only 7.2 and 1.8 days, respectively. 2004 Antiviral research Abstract HIV D30N;N88D 44;53 48;57 15168798 Persistence of mutations during replication of an HIV library containing combinations of selected protease mutations. However, the mutations M36I, M46I and I84V were relatively persistent: t(1/2) = 34.2, 28.1 and 30.6 days, respectively. 2004 Antiviral research Abstract HIV I84V;M36I;M46I 38;23;29 42;27;33 15168798 Persistence of mutations during replication of an HIV library containing combinations of selected protease mutations. Other amino acid substitutions, i.e., L10I, I54V, L63P, A71V and V82A, were well retained (t(1/2) > 36 days). 2004 Antiviral research Abstract HIV A71V;I54V;L10I;L63P;V82A 56;44;38;50;65 60;48;42;54;69 15168798 Persistence of mutations during replication of an HIV library containing combinations of selected protease mutations. The frequency of the amino acid substitutions V82T/I and L90M decreased rapidly with a short half life (t(1/2) < 10 days). 2004 Antiviral research Abstract HIV L90M;V82I;V82T 57;46;46 61;52;52 15180540 A novel class of HIV-1 inhibitors that targets the viral envelope and inhibits CD4 receptor binding. In particular, two substitutions, M426L and M475I, are situated at or near the CD4 binding pocket of gp120. 2004 Current pharmaceutical design Abstract HIV M426L;M475I 34;44 39;49 gp120 101 106 15183061 N-linked glycosylation in the CXCR4 N-terminus inhibits binding to HIV-1 envelope glycoproteins. Binding of stromal cell-derived factor (SDF)-1alpha, the natural ligand of CXCR4, and SDF-1alpha-induced signaling were reduced by the N11Q mutation. 2004 Virology Abstract HIV N11Q 135 139 15183061 N-linked glycosylation in the CXCR4 N-terminus inhibits binding to HIV-1 envelope glycoproteins. However, the binding of R5 gp120 to N11Q-CXCR4 and entry of R5 HIV-1 viruses into cells expressing N11Q-CXCR4 were 20- and 100- to 1000-fold less efficient, respectively, than the levels achieved using X4 gp120 or X4 HIV-1 viruses. 2004 Virology Abstract HIV N11Q;N11Q 36;99 40;103 gp120;gp120 27;205 32;210 15183061 N-linked glycosylation in the CXCR4 N-terminus inhibits binding to HIV-1 envelope glycoproteins. Mutation of the N-glycosylation site N11 in CXCR4 (N11Q-CXCR4) enhanced CD4-dependent binding of X4 and R5 gp120s and allowed more efficient entry of viruses pseudotyped with X4 or R5 HIV-1 envelope glycoproteins. 2004 Virology Abstract HIV N11Q 51 55 Env;gp120 190;107 198;113 15183338 Primer unblocking by HIV-1 reverse transcriptase and resistance to nucleoside RT inhibitors (NRTIs). In addition, point mutations conferring resistance to NNRTIs (Y181C and L100I) or NRTIs (K65R, L74V, and M184V) partially resensitize the resistant viruses to AZT by inhibiting ATP-phosphorolysis. 2004 The international journal of biochemistry & cell biology Abstract HIV K65R;L100I;L74V;M184V;Y181C 89;72;95;105;62 93;77;99;110;68 NNRTI;NRTI 54;82 60;87 15183348 Proteolytic processing of an HIV-1 pol polyprotein precursor: insights into the mechanism of reverse transcriptase p66/p51 heterodimer formation. Processing of the p66 subunit to form p51 apparently proceeds through a p66/p66 RT homodimer intermediate since the L234A mutation in RT, a mutation that prevents RT dimerization, resulted in the formation of RT p66 only. 2004 The international journal of biochemistry & cell biology Abstract HIV L234A 116 121 RT;RT;RT;RT 80;134;163;209 82;136;165;211 15185725 Design and synthesis of novel dihydroxyindole-2-carboxylic acids as HIV-1 integrase inhibitors. All compounds were tested against purified IN and the C65S mutant in enzyme-based assays. 2004 Antiviral chemistry & chemotherapy Abstract HIV C65S 54 58 IN 43 45 15196815 Molecular mechanism of dioxolane nucleosides against 3TC resistant M184V mutant HIV. In this study, the active site of the 3TC-resistant (M184V) RT is constructed by a computational method, which clearly shows that the side chain of Val184 occupies the binding site for the nucleoside triphosphates. 2004 Antiviral research Abstract HIV M184V 53 58 RT 60 62 15196815 Molecular mechanism of dioxolane nucleosides against 3TC resistant M184V mutant HIV. Therefore, the distance between the side chain of Val184 and the sugar moiety of the nucleoside triphosphate must be closely related to the cross-resistance by M184V RT. 2004 Antiviral research Abstract HIV M184V 160 165 RT 166 168 15206508 Emtricitabine (FTC) for the treatment of HIV infection. FTC may be dosed once daily and in vitro is less associated with the M184V mutation, which is classically associated with failure of treatment with lamivudine. 2004 International journal of clinical practice Abstract HIV M184V 69 74 15207625 Tryptophan scanning mutagenesis of aromatic residues within the polymerase domain of HIV-1 reverse transcriptase: critical role of Phe-130 for p51 function and second-site revertant restoring viral replication capacity. HIV-1 carrying RT mutations F124W or F130W replicated very poorly, but compensatory changes (K83R for F124W, and T58S for F130W) were selected upon passaging the virus in cell culture. 2004 Virology Abstract HIV F124W;F124W;F130W;F130W;K83R;T58S 28;102;37;122;93;113 33;107;42;127;98;117 RT 15 17 15207625 Tryptophan scanning mutagenesis of aromatic residues within the polymerase domain of HIV-1 reverse transcriptase: critical role of Phe-130 for p51 function and second-site revertant restoring viral replication capacity. However, RTs bearing mutations F77W or Y146W had a dNTP-binding defect, rendering nonviable viruses. 2004 Virology Abstract HIV F77W;Y146W 31;39 35;44 RT 9 12 15207625 Tryptophan scanning mutagenesis of aromatic residues within the polymerase domain of HIV-1 reverse transcriptase: critical role of Phe-130 for p51 function and second-site revertant restoring viral replication capacity. The amino acid substitution F130W diminishes the stability of the 51-kDa subunit of the RT (p51) and impairs polyprotein processing in virus-infected cells, an effect that can be mitigated when T58S is found in p51. 2004 Virology Abstract HIV F130W;T58S 28;194 33;198 RT 88 90 15207625 Tryptophan scanning mutagenesis of aromatic residues within the polymerase domain of HIV-1 reverse transcriptase: critical role of Phe-130 for p51 function and second-site revertant restoring viral replication capacity. Viruses containing mutations Y56W, F61W, F87W, F116W, Y127W, Y144W, F171W, Y181W, Y183W, Y188W, F227W, or Y232W in their RT-coding regions were viable and showed replication capacities similar or slightly reduced in comparison with the wild-type HIV-1. 2004 Virology Abstract HIV F116W;F171W;F227W;F61W;F87W;Y127W;Y144W;Y181W;Y183W;Y188W;Y232W;Y56W 47;68;96;35;41;54;61;75;82;89;106;29 52;73;101;39;45;59;66;80;87;94;111;33 RT 121 123 15207637 Conformation of gp120 determines the sensitivity of HIV-1 DH012 to the entry inhibitor IC9564. A T198P mutation in the gp120 of the HIV-1 primary isolate, DH012, drastically increases IC9564 sensitivity, which can be reversed by growing the virus in the presence of IC9564. 2004 Virology Abstract HIV T198P 2 7 gp120 24 29 15207637 Conformation of gp120 determines the sensitivity of HIV-1 DH012 to the entry inhibitor IC9564. On the other hand, the IC9564 escape variant with the P198S mutation is resistant to these conformational antibodies and highly sensitive to the potent neutralizing antiserum, C1206, which recognizes a conformational epitope involving the sequences from V1, V2, and V3 regions in gp120. 2004 Virology Abstract HIV P198S 54 59 gp120 280 285 15207637 Conformation of gp120 determines the sensitivity of HIV-1 DH012 to the entry inhibitor IC9564. The reversed resistant variants contain a P198S mutation that fully confers the drug-resistant phenotype. 2004 Virology Abstract HIV P198S 42 47 15207637 Conformation of gp120 determines the sensitivity of HIV-1 DH012 to the entry inhibitor IC9564. This conformational effect is evidenced by the fact that the T198P mutation significantly increases the neutralizing activity of the conformational antibodies, 1b12 and 48d. 2004 Virology Abstract HIV T198P 61 66 15210352 Camelized rabbit-derived VH single-domain intrabodies against Vif strongly neutralize HIV-1 infectivity. Non-specific binding of VH by its interface for the light chain variable domain (VL) was prevented through amino acid mutations in framework 2 and 4 (Val37F, G44E, L45R, W47G and W103R). 2004 Journal of molecular biology Abstract HIV G44E;L45R;W103R;W47G 158;164;179;170 162;168;184;174 15220416 The phenylmethylthiazolylthiourea nonnucleoside reverse transcriptase (RT) inhibitor MSK-076 selects for a resistance mutation in the active site of human immunodeficiency virus type 2 RT. G112E, however, is distal to the putative NNRTI-binding site in HIV-2 RT but close to the active site, implying a novel molecular mode of action and mechanism of resistance. 2004 Journal of virology Abstract HIV G112E 0 5 NNRTI;RT 42;70 47;72 15220416 The phenylmethylthiazolylthiourea nonnucleoside reverse transcriptase (RT) inhibitor MSK-076 selects for a resistance mutation in the active site of human immunodeficiency virus type 2 RT. Mapping of the resistance mutations to the HIV-2 RT structure ascertained that A101P is located at a position equivalent to the nonnucleoside RT inhibitor (NNRTI)-binding site of HIV-1 RT. 2004 Journal of virology Abstract HIV A101P 79 84 NNRTI;RT;RT;RT 156;49;142;185 161;51;144;187 15220416 The phenylmethylthiazolylthiourea nonnucleoside reverse transcriptase (RT) inhibitor MSK-076 selects for a resistance mutation in the active site of human immunodeficiency virus type 2 RT. MSK-076 selected for A101P and G112E mutations in HIV-2 RT and for K101E, Y181C, and G190R mutations in HIV-1 RT. 2004 Journal of virology Abstract HIV A101P;G112E;G190R;K101E;Y181C 21;31;85;67;74 26;36;90;72;79 RT;RT 56;110 58;112 15220416 The phenylmethylthiazolylthiourea nonnucleoside reverse transcriptase (RT) inhibitor MSK-076 selects for a resistance mutation in the active site of human immunodeficiency virus type 2 RT. The selected mutated strains of HIV-2 were fully resistant to MSK-076, and the mutant HIV-2 RT enzymes into which the A101P and/or G112E mutation was introduced by site-directed mutagenesis showed more than 50-fold resistance to MSK-076. 2004 Journal of virology Abstract HIV A101P;G112E 118;131 123;136 RT 92 94 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. Both HXB2(D67N/K219Q) and HXB2(D67N) were more fit than HXB2(WT) in the presence of either low or high AZT concentrations, likely reflecting low-level resistance to AZT that is not detectable by phenotypic testing. 2004 Journal of virology Abstract HIV D67N;K219Q;D67N 10;15;31 14;20;35 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. Four site-directed mutants with D67N, K219Q, K219E, and D67N/K219Q were also made in HIV-1(HXB2). 2004 Journal of virology Abstract HIV D67N;D67N;K219E;K219Q;K219Q 32;56;45;61;38 36;60;50;66;43 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. In the absence of AZT, the fitness cost conferred by D67N or K219Q was modest. 2004 Journal of virology Abstract HIV D67N;K219Q 53;61 57;66 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. In vitro selection of AZT resistance showed that viruses with D67N and/or K219Q/E acquired AZT resistance mutations more rapidly than WT viruses (36 days compared to 54 days; P = 0.003). 2004 Journal of virology Abstract HIV D67N;K219E;K219Q 62;74;74 66;81;81 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. Of these viruses, 9 (25.7%) had only secondary TAMs (D67N, K219Q, M41L, or F77L), and all were found to be sensitive to zidovudine (AZT) and other drugs. 2004 Journal of virology Abstract HIV D67N;F77L;K219Q;M41L 53;75;59;66 57;79;64;70 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. Our results demonstrate that viruses with unique patterns of TAMs, including D67N and/or K219Q/E, are commonly found among newly diagnosed persons and illustrate the expanding diversity of revertant viruses in this population. 2004 Journal of virology Abstract HIV D67N;K219E;K219Q 77;89;89 81;96;96 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. The modest fitness cost conferred by D67N and K219Q supports persistence of these mutants in the untreated population and highlights the potential for secondary transmission. 2004 Journal of virology Abstract HIV D67N;K219Q 37;46 41;51 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. Through the analysis of resistance mutations in 1082 newly diagnosed antiretroviral-naive persons from the United States, we found that 35 of 48 (72.9%) persons infected with HIV-1 containing thymidine analog mutations (TAMs) had viruses that lacked a primary mutation (T215Y/F, K70R, or Q151M). 2004 Journal of virology Abstract HIV K70R;Q151M;T215F;T215Y 279;288;270;270 283;293;277;277 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. To investigate the factors associated with the rapid selection of AZT mutations in these viruses, we evaluated fitness differences among HXB2(WT) and HXB2(D67N) or HXB2(D67N/K219Q) in the presence of AZT. 2004 Journal of virology Abstract HIV D67N;K219Q;D67N 169;174;155 173;179;159 15220429 Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. Two viruses had D67N, three had D67N and K219Q/E, and three were WT. 2004 Journal of virology Abstract HIV D67N;D67N;K219E;K219Q 16;32;41;41 20;36;48;48 15239667 Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126) active in vitro against HIV-1 wild type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations. In cell-based assays, the new derivatives showed activities against HIV-1 wild type and NNRTI-resistant mutants [Y181C, K103N-Y181C, and triple mutant (K103R, V179D, P225H) highly resistant to efavirenz] superior to that of the parent indole derivative 1. 2004 Journal of medicinal chemistry Abstract HIV K103N;K103R;P225H;V179D;Y181C;Y181C 120;152;166;159;113;126 125;157;171;164;118;131 NNRTI 88 93 15242535 Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012. In contrast, the K103N mutation emerges more slowly, but often remains detectable 6-8 weeks after NVP. 2004 AIDS research and human retroviruses Abstract HIV K103N 17 22 15242535 Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012. The Y181C NVPR mutation often fades from detection by 6-8 weeks. 2004 AIDS research and human retroviruses Abstract HIV Y181C 4 9 15242535 Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012. Y181C was the most common NVPR mutation detected at 7 days, whereas K103N was the most common NVPR mutation detected at 6-8 weeks. 2004 AIDS research and human retroviruses Abstract HIV K103N;Y181C 68;0 73;5 15242545 V118I substitution in the reverse transcriptase gene of HIV type 1 CRF02_AG strains infecting drug-naive individuals in Cameroon. Analysis of the RT genes for resistance-associated substitutions revealed two sequences containing a V118I substitution. 2004 AIDS research and human retroviruses Abstract HIV V118I 101 106 RT 16 18 15242545 V118I substitution in the reverse transcriptase gene of HIV type 1 CRF02_AG strains infecting drug-naive individuals in Cameroon. Even though no other resistance-associated substitutions were found, the presence of V118I, which is implicated in resistance to reverse transcriptase inhibitors, in CRF02_AG strains infecting drug-naive individuals should be considered when introducing these antiretrovirals in areas where CRF02_AG is the predominant subtype, such as Cameroon. 2004 AIDS research and human retroviruses Abstract HIV V118I 85 90 RT 129 150 15242547 Compartmentalization of drug resistance-associated mutations in a treatment-naive HIV-infected female. On the other hand vaginal virus contained L63P and M184V mutations in protease and reverse transcriptase, respectively. 2004 AIDS research and human retroviruses Abstract HIV L63P;M184V 42;51 46;56 RT;PR 83;70 104;78 15242547 Compartmentalization of drug resistance-associated mutations in a treatment-naive HIV-infected female. Plasma virus had no mutation in reverse transcriptase and one mutation in protease (L63P). 2004 AIDS research and human retroviruses Abstract HIV L63P 84 88 RT;PR 32;74 53;82 15246104 Effect of stereochemistry on the anti-HIV activity of chiral thiourea compounds. The lead compounds in the respective groups were further tested against the NNRTI-resistant HIV strains, A17 (Y181C mutant), and A17Var (Y181C+K103N mutant) and RT MDR (V106N). 2004 Bioorganic & medicinal chemistry Abstract HIV K103N;V106N;Y181C;Y181C 143;169;110;137 148;174;116;141 NNRTI;RT 76;161 81;163 15247339 Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. 2004 The New England journal of medicine Abstract HIV G190A;K103N;Y181C 243;236;254 248;241;259 NNRTI 24 59 15247558 Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role of mutagenically separated polymerase chain reaction as a tool for monitoring zidovudine-resistant HIV-1 in resource-limited settings. Concordant rates of detecting M41L and K70R mutations by the 2 methods were 96.9% (93/96) and 92.7% (89/96), respectively. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M41L 39;30 43;34 15247558 Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role of mutagenically separated polymerase chain reaction as a tool for monitoring zidovudine-resistant HIV-1 in resource-limited settings. The M41L and K70R MS-PCR could detect 86.4% of AZT-resistant strains with any resistance mutation, which was determined by the sequencing method. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M41L 13;4 17;8 15247558 Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role of mutagenically separated polymerase chain reaction as a tool for monitoring zidovudine-resistant HIV-1 in resource-limited settings. The M41L and K70R MS-PCR is potentially a useful tool to monitor the spread of AZT-resistant HIV-1 in resource-limited countries. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M41L 13;4 17;8 15247558 Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role of mutagenically separated polymerase chain reaction as a tool for monitoring zidovudine-resistant HIV-1 in resource-limited settings. Then 292 drug-naive individuals were screened for the presence of drug-resistant HIV-1 by the MS-PCR assay and it was found that 2 individuals (0.7%) carried viruses with either the M41L or K70R mutation. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M41L 190;182 194;186 15247558 Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role of mutagenically separated polymerase chain reaction as a tool for monitoring zidovudine-resistant HIV-1 in resource-limited settings. This study first sequenced the reverse transcriptase region of HIV-1 in 112 infected individuals who had been treated with zidovudine (AZT)/didanosine or AZT/zalcitabine as dual therapy at a government hospital in northern Thailand and then compared the above sequence method with mutagenically separated polymerase chain reaction (MS-PCR) for detecting M41L and K70R mutations. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M41L 363;354 367;358 RT;Pol 31;305 52;315 15249568 Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups, respectively (P =.06). 2004 JAMA Abstract HIV K65R 23 27 15249669 Structure of HIV-1 reverse transcriptase bound to an inhibitor active against mutant reverse transcriptases resistant to other nonnucleoside inhibitors. Modeling the asparagine mutation of lysine 103 shows that a hydrogen bond between it and tyrosine 188 could form as readily in the CP-94,707 complex as it does in the apoenzyme structure, providing an explanation for the activity of this inhibitor against this clinically important mutant. 2004 Proc Natl Acad Sci U S A Abstract HIV K103N 13 46 15257882 Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany. 10.5% showed mutations indicating nucleoside reverse transcriptase inhibitor- (NRTI) resistance (M41L, E44D, D67N, T69D/N, L74V, V118I, M184V, L210W, K219Q), 2.8% showed non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (K103N, V108I, Y181C), and 2.1% showed protease-inhibitor- (PI) associated resistance (V82A, L90M), respectively. 2004 European journal of medical research Abstract HIV D67N;E44D;K103N;K219Q;L210W;L74V;L90M;M184V;M41L;T69D;T69N;V108I;V118I;V82A;Y181C 109;103;237;150;143;123;329;136;97;115;115;244;129;323;251 113;107;242;155;148;127;333;141;101;121;121;249;134;327;256 NNRTI;NRTI;PR;NNRTI;NRTI;PI 170;34;275;218;79;296 206;66;283;223;83;298 15257882 Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany. Multi-class-resistance was found in 2.1%, mutations indicating revertant variants of resistant strains were found in 4.2% (T215C/E/L/S). 2004 European journal of medical research Abstract HIV T215C;T215E;T215L;T215S 123;123;123;123 134;134;134;134 15258963 Resistance profiles observed in virological failures after 24 weeks of amprenavir/ritonavir containing regimen in protease inhibitor experienced patients. Among these patients, the selection of mutations previously described with the use of APV as first PI (V32I, L33F, M46I/L, I50V, 54M/L, and I84V) was observed. 2004 Journal of medical virology Abstract HIV I50V;I84V;L33F;M46I;M46L;V32I 123;140;109;115;115;103 127;144;113;121;121;107 PI 99 101 15258963 Resistance profiles observed in virological failures after 24 weeks of amprenavir/ritonavir containing regimen in protease inhibitor experienced patients. However, in some cases, mutations classically described after the use of other PIs (V82F and L90M) were selected but always with APV-specific mutations. 2004 Journal of medical virology Abstract HIV L90M;V82F 93;84 97;89 PI 79 82 15258963 Resistance profiles observed in virological failures after 24 weeks of amprenavir/ritonavir containing regimen in protease inhibitor experienced patients. Several genotypic resistance pathways in protease gene have been described to be associated to unboosted APV failure (I50V, V32I + I47V, I54L/M, or less commonly I84V, which may be accompanied by one ore more accessory mutations such as L10F, L33F, M46I/L). 2004 Journal of medical virology Abstract HIV I47V;I50V;I54L;I54M;I84V;L10F;L33F;M46I;M46L;V32I 131;118;137;137;162;237;243;249;249;124 135;122;143;143;166;241;247;255;255;128 PR 41 49 15258964 Evolution of genotypic and phenotypic resistance to Enfuvirtide in HIV-infected patients experiencing prolonged virologic failure. Mutations within the HR1 env region were selected (N43D in three and G36V/D in one), resulting in high-level phenotypic resistance to ENF. 2004 Journal of medical virology Abstract HIV G36D;G36V;N43D 69;69;51 75;75;56 Env 25 28 15259893 The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients. HIV variants resistant to saquinavir and ritonavir usually contain L90M and V82A substitutions, respectively. 2004 Antiviral therapy Abstract HIV L90M;V82A 67;76 71;80 15259893 The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients. Other mutations (D30N, G48V, I50V or I50L) are relatively specific for particular PIs and are less likely to produce cross resistance. 2004 Antiviral therapy Abstract HIV D30N;G48V;I50L;I50V 17;23;37;29 21;27;41;33 PI 82 85 15259893 The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients. Resistance during exposure to amprenavir can follow development of I50V, which also may confer resistance to lopinavir. 2004 Antiviral therapy Abstract HIV I50V 67 71 15259893 The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients. Resistance to nelfinavir is primarily associated with D30N but may alternatively be found with L90M. 2004 Antiviral therapy Abstract HIV D30N;L90M 54;95 58;99 15259894 Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients. RESULTS: The strongest association with decrease in viral load was observed with a set of seven mutations (TDF mutation score) that consisted of M41L, E44D, D67N, T69D/N/S, L74V, L210W and T215Y/F RT mutations. 2004 Antiviral therapy Abstract HIV D67N;E44D;L210W;L74V;M41L;T215F;T215Y;T69D;T69N;T69S 157;151;179;173;145;189;189;163;163;163 161;155;184;177;149;196;196;171;171;171 RT 197 199 15259894 Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients. The RT K65R mutation and the insertions at codon 69 were not included in the analysis due to low prevalences. 2004 Antiviral therapy Abstract HIV K65R 7 11 RT 4 6 15262499 Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains bearing a dipeptide insertion in the fingers subdomain of the reverse transcriptase and mutations at codons 67 and 215. A two-serine insertion at position 69 (i69SS) of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) appears to be critical to enhance multi-nucleoside RT inhibitor resistance (MNR) in the sequence context of multiple zidovudine (AZT) resistance mutations (i.e., M41L, L210W, T215Y). 2004 Virology Abstract HIV L210W;M41L;T215Y 288;282;295 293;286;300 RT;RT;RT 93;116;171 114;118;173 15262499 Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains bearing a dipeptide insertion in the fingers subdomain of the reverse transcriptase and mutations at codons 67 and 215. In this study, we measured the replication capacity relative to the wild-type (WT) HIV-1 of a series of recombinant viruses carrying the i69SS in the background of a clinical isolate with MNR in which we introduced mutations D67N, Y215T, Y215S, or Y215N. 2004 Virology Abstract HIV D67N;Y215N;Y215S;Y215T 225;248;238;231 229;253;243;236 15262499 Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains bearing a dipeptide insertion in the fingers subdomain of the reverse transcriptase and mutations at codons 67 and 215. Interestingly, the presence of the insertion together with mutation T215Y in an otherwise WT sequence background was not sufficient to confer high-level resistance to AZT, although its replication capacity was clearly impaired. 2004 Virology Abstract HIV T215Y 68 73 15262499 Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains bearing a dipeptide insertion in the fingers subdomain of the reverse transcriptase and mutations at codons 67 and 215. While the addition of D67N had a minor effect on replication capacity, the reversion of Tyr-215 to Thr, Ser, or Asn was sufficient to increase the virus ability to replicate in a drug-free environment. 2004 Virology Abstract HIV D67N 22 26 15266257 K65R-associated virologic failure in HIV-infected patients receiving tenofovir-containing triple nucleoside/nucleotide reverse transcriptase inhibitor regimens. High rates of early virologic failure associated with the emergence of the K65R mutation in HIV-1 reverse transcriptase (RT) have been reported among HIV-infected patients who received novel, tenofovir-containing, triple-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI/NtRTI) regimens as their initial therapy. 2004 MedGenMed Abstract HIV K65R 75 79 RT;RT;NRTI;RT 98;243;276;121 119;264;280;123 HIV infections 150 162 15266257 K65R-associated virologic failure in HIV-infected patients receiving tenofovir-containing triple nucleoside/nucleotide reverse transcriptase inhibitor regimens. This review surveys the findings of prospective and retrospective studies in this regard, examines the significance of the K65R mutation and other factors associated with reports of early virologic failure among patients receiving tenofovir-containing NRTI/NtRTI regimens, and discusses clinical approaches to preventing and managing HIV drug resistance and treatment failure associated with the K65R mutation. 2004 MedGenMed Abstract HIV K65R;K65R 123;396 127;400 NRTI 252 256 15273111 Nucleotide and amino acid polymorphisms at drug resistance sites in non-B-subtype variants of human immunodeficiency virus type 1. Subtype A viruses possessed a V179I substitution in reverse transcriptase (RT). 2004 Antimicrobial agents and chemotherapy Abstract HIV V179I 30 35 RT;RT 52;75 73;77 15273111 Nucleotide and amino acid polymorphisms at drug resistance sites in non-B-subtype variants of human immunodeficiency virus type 1. Subtype C was distinguished by silent substitutions at codons 106 (GTA-->GTG) and 219 (AAA-->AAG) in RT and codon 48 (GGG-->GGA) in PR. 2004 Antimicrobial agents and chemotherapy Abstract HIV K219K;R48R 82;108 97;128 PR;RT 132;101 134;103 15273111 Nucleotide and amino acid polymorphisms at drug resistance sites in non-B-subtype variants of human immunodeficiency virus type 1. These included silent substitutions (CTC-->CTT, CTA, TTA) and an amino acid mutation, L10I. 2004 Antimicrobial agents and chemotherapy Abstract HIV L10I 86 90 15273111 Nucleotide and amino acid polymorphisms at drug resistance sites in non-B-subtype variants of human immunodeficiency virus type 1. Variations relative to subtype B were seen at RT position 215 (ACC-->ACT) for subtypes A and A/E. 2004 Antimicrobial agents and chemotherapy Abstract HIV T215T 58 73 RT 46 48 15279592 The challenge of antiretroviral-drug-resistant HIV: is there any possible clinical advantage? Particularly, the effects on reduction of replication capacity related to M184V mutation in reverse transcriptase are analyzed. 2004 Current HIV research Abstract HIV M184V 74 79 RT 92 113 15280484 Antiretroviral drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase increase template-switching frequency. In contrast, substitutions in the RNase H domain (H539N, D549N) decreased the frequency of RT template switching by twofold. 2004 Journal of virology Abstract HIV D549N;H539N 57;50 62;55 RT 91 93 15280484 Antiretroviral drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase increase template-switching frequency. Several mutations associated with resistance to antiviral nucleoside analogs (K65R, L74V, E89G, Q151N, and M184I) dramatically increased RT template-switching frequencies by two- to sixfold in a single replication cycle. 2004 Journal of virology Abstract HIV E89G;K65R;L74V;M184I;Q151N 90;78;84;107;96 94;82;88;112;101 RT 137 139 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. CONCLUSION: These analyses should assist in the creation of rules for genotypic drug resistance algorithms for a better reflection of the impact of individual TAM and also the impact of M184I/V on resistance. 2004 AIDS (London, England) Abstract HIV M184I;M184V 186;186 193;193 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. DESIGN: An HIV genotypic/phenotypic database with over 27 000 samples was used to obtain the median fold change (5-95th percentile) in NRTI phenotypic susceptibility for viruses from patients containing individual TAM with or without the M184I or V mutation and for wild-type patient viruses. 2004 AIDS (London, England) Abstract HIV M184I 238 243 NRTI 135 139 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. For didanosine and abacavir, the presence of the M184V mutation and a single TAM did not result in a fold-change increase associated with decreased drug susceptibility. 2004 AIDS (London, England) Abstract HIV M184V 49 54 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. In the presence of the M184I/V mutation, re-sensitization to some drugs, including zidovudine, stavudine and tenofovir was observed despite the presence of a TAM. 2004 AIDS (London, England) Abstract HIV M184I;M184V 23;23 30;30 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. M41L or K219Q/E/H/R). 2004 AIDS (London, England) Abstract HIV K219E;K219H;K219Q;K219R;M41L 8;8;8;8;0 19;19;19;19;4 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. OBJECTIVES: To analyse the impact of the M184I/V mutation and individual thymidine-associated mutations (TAM) on nucleoside reverse transcriptase inhibitor (NRTI) phenotypic susceptibility and compare these results with those obtained using commercial and public algorithms. 2004 AIDS (London, England) Abstract HIV M184I;M184V 41;41 48;48 NRTI;NRTI 113;157 145;161 15280780 Phenotypic impact of HIV reverse transcriptase M184I/V mutations in combination with single thymidine analog mutations on nucleoside reverse transcriptase inhibitor resistance. These data provide additional evidence that retaining lamivudine in those treatment regimens in which TAM can be selected may provide some therapeutic benefit by maintaining the M184V mutation. 2004 AIDS (London, England) Abstract HIV M184V 178 183 15301542 Investigation of N-terminal domain charged residues on the assembly and stability of HIV-1 CA. Previous in vivo experiments generated two N-terminal domain charge change mutants (E45A and E128A/R132A) that showed an increase in stability of the viral core. 2004 Biochemistry Abstract HIV E128A;E45A;R132A 93;84;99 98;89;104 15301542 Investigation of N-terminal domain charged residues on the assembly and stability of HIV-1 CA. We constructed a number of charge mutants in this region (E45A, E45K, E128A, R132A, E128A/R132A, K131A, and K131E) and evaluated their effect on protein stability in addition to their effect on the rate of CA assembly. 2004 Biochemistry Abstract HIV E128A;E128A;E45A;E45K;K131A;K131E;R132A;R132A 70;84;58;64;97;108;90;77 75;89;62;68;102;113;95;82 Capsid 206 208 15302136 2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors. The compounds had significantly reduced activity against the characteristic NNRTI-resistant virus mutants (bearing the K103N and Y181C RT mutations), thereby acting as non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors (NNRTIs). 2004 Antiviral research Abstract HIV K103N;Y181C 119;129 124;134 RT;NNRTI;NNRTI;RT;RT 189;76;228;135;212 210;81;234;137;214 15307920 Evolutionary repair of HIV type 1 gp41 with a kink in the N-terminal helix leads to restoration of the six-helix bundle structure. Biophysical studies show that the Ile559Pro mutation essentially disrupts the folding of a recombinant gp41 ectodomain core into a six-helix bundle structure. 2004 AIDS research and human retroviruses Abstract HIV I559P 34 43 gp41 103 107 15307920 Evolutionary repair of HIV type 1 gp41 with a kink in the N-terminal helix leads to restoration of the six-helix bundle structure. In the escape virus, which contains a Pro559Leu first-site pseudoreversion, the local helical structure and, as a consequence, Env biosynthesis and function are restored. 2004 AIDS research and human retroviruses Abstract HIV P559L 38 47 Env 127 130 15307920 Evolutionary repair of HIV type 1 gp41 with a kink in the N-terminal helix leads to restoration of the six-helix bundle structure. The Ile559Gly and Ile559Pro mutations adversely affect Env biosynthesis and Env incorporation into virions. 2004 AIDS research and human retroviruses Abstract HIV I559G;I559P 4;18 13;27 Env;Env 55;76 58;79 15307920 Evolutionary repair of HIV type 1 gp41 with a kink in the N-terminal helix leads to restoration of the six-helix bundle structure. Viruses containing the Ile559Gly and Ile559Pro substitutions replicate poorly, but an evolutionary route is described that restores replication competence. 2004 AIDS research and human retroviruses Abstract HIV I559G;I559P 23;37 32;46 15316339 Characterization of determinants of genotypic and phenotypic resistance to enfuvirtide in baseline and on-treatment HIV-1 isolates. RESULTS: HIV-1 gp41 aa 36-45 were highly conserved in virus from ENF-naive patients, except for a 15% incidence of N42S which did not reduce sensitivity to ENF. 2004 AIDS (London, England) Abstract HIV N42S 115 119 gp41 15 19 15320704 Resistance to HIV protease inhibitors: mechanisms and clinical consequences. Specific changes are characteristically linked to resistance to each of these compounds (i.e., D30N for nelfinavir, I50L for atazanavir or I50V for amprenavir). 2004 Current drug metabolism Abstract HIV D30N;I50L;I50V 95;116;139 99;120;143 15328115 Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. 2004 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y188C;Y188L 52;62;71 57;67;76 15328124 Impact of nelfinavir resistance mutations on in vitro phenotype, fitness, and replication capacity of human immunodeficiency virus type 1 with subtype B and C proteases. We showed that D30N has significantly more impact in subtype C than in subtype B counterparts, accounting for the reported low prevalence of this mutation in patients failing nelfinavir-based regimens. 2004 Antimicrobial agents and chemotherapy Abstract HIV D30N 15 19 15331732 Effects of the Delta67 complex of mutations in human immunodeficiency virus type 1 reverse transcriptase on nucleoside analog excision. HIV-1 RT containing the Delta67 complex of mutations was not able to excise as broad a range of NRTIs as the fingers insertion variant SSGR/T215Y, but it was able to polymerize efficiently with low concentrations of deoxynucleoside triphosphates and seems to be able to excise AZTMP and PMPA at lower ATP concentrations than AZT-R or SSGR/T215Y, suggesting that a virus containing the Delta67 complex of mutations would replicate reasonably well in quiescent cells, even in the presence of AZT. 2004 Journal of virology Abstract HIV T215Y;T215Y 140;339 145;344 NRTI;RT 96;6 101;8 15331732 Effects of the Delta67 complex of mutations in human immunodeficiency virus type 1 reverse transcriptase on nucleoside analog excision. HIV-1 variants containing amino acid substitutions within the coding region of HIV-1 reverse transcriptase (RT), such as the 3'-azido-3'-deoxythymidine (AZT)-resistant variant AZT-R (M41L/D67N/K70R/T215Y/K219Q) and a variant containing an insertion in the fingers domain (S69SGR70/T215Y), are resistant to the nucleoside RT inhibitor (NRTI) AZT because of an increase in the level of excision of AZT monophosphate (AZTMP) from the primer. 2004 Journal of virology Abstract HIV M41L;D67N;K219Q;K70R;T215Y;T215Y 183;188;204;193;198;281 187;192;209;197;203;286 RT;NRTI;RT;RT 85;335;108;321 106;339;110;323 15331753 A naturally occurring variation in the proline-rich region does not attenuate human immunodeficiency virus type 1 nef function. We analyzed human immunodeficiency virus type 1 (HIV-1) Nef variants to further evaluate the functional relevance of the R71T substitution previously proposed to attenuate viral replication (Fackler et al., Curr. 2004 Journal of virology Abstract HIV R71T 121 125 Nef 56 59 15332266 High frequency of selection of K65R and Q151M mutations in HIV-2 infected patients receiving nucleoside reverse transcriptase inhibitors containing regimen. Compared with HIV-1 infection, there is a high frequency of selection of Q151M mutation in HIV-2 infected patients receiving various combinations of NRTIs. 2004 Journal of medical virology Abstract HIV Q151M 73 78 NRTI 149 154 HIV infections 14 29 15332266 High frequency of selection of K65R and Q151M mutations in HIV-2 infected patients receiving nucleoside reverse transcriptase inhibitors containing regimen. In 8/9 cases, Q151M mutation was associated with other substitutions at positions known to be involved in HIV-1 resistance: K65R (n = 6), D67N (n = 1), N69S or T (n = 2), K70R (n = 3), M184V (n = 4), S215Y (n = 1). 2004 Journal of medical virology Abstract HIV D67N;K65R;K70R;M184V;N69S;Q151M;S215Y 138;124;171;185;152;14;200 142;128;175;190;156;19;205 15332266 High frequency of selection of K65R and Q151M mutations in HIV-2 infected patients receiving nucleoside reverse transcriptase inhibitors containing regimen. Selection of Q151M mutation was observed in nine out of 34 isolates (26%) after a median NRTIs exposure of 41 months (range: 12-77). 2004 Journal of medical virology Abstract HIV Q151M 13 18 NRTI 89 94 15332433 2004: which HIV-1 drug resistance mutations are common in clinical practice? For example, only the nucleoside reverse transcriptase inhibitor (NRTI) mutations M184V, M41L T215Y, D67N, K70R and L210W, non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K103N and Y181C, and protease inhibitor (PI) mutation L90M, occur in more than 10% of samples tested for resistance in this population. 2004 AIDS reviews Abstract HIV D67N;K103N;K70R;L210W;L90M;M184V;M41L;T215Y;Y181C 101;188;107;116;242;82;89;94;198 105;193;111;121;246;87;93;99;203 NNRTI;NRTI;PR;NNRTI;NRTI;PI 123;22;209;171;66;229 159;54;217;176;70;231 15333937 Crystallization of a non-B and a B mutant HIV protease. the subtype B mutant, with mutations Q7K, S37N, R41K, K45R, I54V, L63P, A71V, V82A and L90M, and the subtype F (wild type), naturally carrying mutations Q7K, I15V, E35D, M36I, S37N, R41K, R57K, D60E, Q61N, I62V, L63S, I64L and L89M, with respect to the B consensus sequence. 2004 Acta crystallographica. Section D, Biological crystallography Abstract HIV A71V;D60E;E35D;I15V;I54V;I62V;I64L;K45R;L63P;L63S;L89M;L90M;M36I;Q61N;Q7K;Q7K;R41K;R41K;R57K;S37N;S37N;V82A 72;194;164;158;60;206;218;54;66;212;227;87;170;200;37;153;48;182;188;42;176;78 76;198;168;162;64;210;222;58;70;216;231;91;174;204;40;156;52;186;192;46;180;82 15345326 Induction of cellular resistance to nucleoside reverse transcriptase inhibitors by the wild-type breast cancer resistance protein. However, this BCRP was found to have a mutation of Arg to Met at position 482 (BCRP(R482M)). 2004 Biochemical pharmacology Abstract HIV R482M;R482M 84;51 89;77 15345326 Induction of cellular resistance to nucleoside reverse transcriptase inhibitors by the wild-type breast cancer resistance protein. These results indicate that, like BCRP(R482M), BCRP(WT) also plays an important role in cellular resistance to NRTIs. 2004 Biochemical pharmacology Abstract HIV R482M 39 44 NRTI 111 116 15351209 Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naive patients. A 48-h culture in the presence of NVP, however, selected HIV-1 carrying NVP resistance-associated mutations, V106A, V108I, or both, suggesting that minor viral populations of these two isolates had harbored these mutations. 2004 Virology Abstract HIV V106A;V108I 109;116 114;121 15351209 Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naive patients. Direct sequencing showed these two isolates had a novel mutation, K238S, in reverse transcriptase (RT), but did not have any reported NVP resistance-associated mutation. 2004 Virology Abstract HIV K238S 66 71 RT;RT 76;99 97;101 15351209 Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naive patients. Our study identified a novel NVP resistance-associated mutation, K238S, which could be persistently detected by genotypic assay longer than V106A and V108I during off-treatment period. 2004 Virology Abstract HIV K238S;V106A;V108I 65;140;150 70;145;155 15351209 Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naive patients. Replication kinetic studies of recombinant HIV-1 clones suggested that K238S conferred a significant resistance against NVP, especially when accompanied with V106A (530-fold) or V108I (56-fold). 2004 Virology Abstract HIV K238S;V106A;V108I 71;158;178 76;163;183 15351215 In vivo mutational analysis of the N-terminal region of HIV-1 Nef reveals critical motifs for the development of an AIDS-like disease in CD4C/HIV transgenic mice. Despite that, the peripheral CD4+ T cells expressing Nef(G2A) show normal spontaneous proliferation in vivo or after stimulation in vitro, including in an allogenic mixed leukocyte reaction (MLR). 2004 Virology Abstract HIV G2A 57 60 Nef 53 56 15351215 In vivo mutational analysis of the N-terminal region of HIV-1 Nef reveals critical motifs for the development of an AIDS-like disease in CD4C/HIV transgenic mice. Mutation of the myristoylation site (G2A) completely abrogated the development of the AIDS-like organ disease in Tg mice, although partial downregulation of the CD4 cell surface protein and depletion of peripheral CD4+ T-cells, but not of CD4(+)CD8+ thymocytes, still occurred. 2004 Virology Abstract HIV G2A 37 40 15356825 K103N mutation in antiretroviral therapy-naive African patients infected with HIV type 1. We report 3 cases of antiretroviral-naive African immigrants infected with HIV-1 strains possessing the K103N mutation in the reverse transcriptase gene, which confers high-level resistance to all nonnucleoside reverse transcriptase inhibitors. 2004 Clinical infectious diseases Abstract HIV K103N 104 109 NNRTI;RT 197;126 232;147 15369509 Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study. In the 30 failing patients not switched from randomized treatment, we found resistance in two of 12 patients in the RS-arm (M184 V only), four of six patients in the NN-arm [all four had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations], and seven of 12 patients in the ASD-arm (NRTI mutations only). 2004 HIV medicine Abstract HIV M184V 124 131 NNRTI;NNRTI;NRTI 187;235;295 223;240;299 15379553 Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease. The decrease in catalytic efficiency was partially recovered by the addition of mutations M46I and I54V. 2004 Biochemistry Abstract HIV I54V;M46I 99;90 103;94 15379553 Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease. The I84V mutation had the greatest effect on decreasing catalytic efficiency, 10-fold when compared to the pretherapy clone LAI. 2004 Biochemistry Abstract HIV I84V 4 8 15379553 Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease. The M46I and I54V were just as effective at decreasing inhibitor binding as the I84V mutation when compared to V6 and LAI. 2004 Biochemistry Abstract HIV I54V;I84V;M46I 13;80;4 17;84;8 15379553 Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease. This variant possessed the ritonavir-resistance-associated mutations in the active-site (V32I and V82A) and nonactive-site mutations (K20R, L33F, M36I, L63P, A71V, and L90M). 2004 Biochemistry Abstract HIV A71V;K20R;L33F;L63P;L90M;M36I;V32I;V82A 158;134;140;152;168;146;89;98 162;138;144;156;172;150;94;102 15379553 Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease. We have engineered a series of variants containing the nonactive-site mutations M46I and I54V and the active-site mutation I84V. 2004 Biochemistry Abstract HIV I54V;I84V;M46I 89;123;80 93;127;84 15380361 Structure-functional analysis of human immunodeficiency virus type 1 (HIV-1) Vpr: role of leucine residues on Vpr-mediated transactivation and virus replication. Confocal microscopy indicated that Vpr L22A exhibited a distinct condensed nuclear localization pattern different from the nuclear/perinuclear pattern noted with Vprwt. 2004 Virology Abstract HIV L22A 39 43 Vpr 35 38 15380361 Structure-functional analysis of human immunodeficiency virus type 1 (HIV-1) Vpr: role of leucine residues on Vpr-mediated transactivation and virus replication. Further, electrophoretic mobility shift assay (EMSA) revealed that the VprL22A-GR complex had higher DNA-binding activity when compared to the wild type Vpr-GR complex. 2004 Virology Abstract HIV L22A 74 78 Vpr;Vpr 71;153 74;156 15448352 Selected amino acid substitutions in the C-terminal region of human immunodeficiency virus type 1 capsid protein affect virus assembly and release. Eight different mutants (L205A+P207A, L205A, P207A, 223GPG225AAA, G223A, P224A, G225A and V221G) of the infectious clone pNL4-3 were constructed. 2004 The Journal of general virology Abstract HIV G223A;G225A;L205A;L205A;P207A;P207A;P224A;V221G 66;80;25;38;31;45;73;90 71;85;30;43;36;50;78;95 15448352 Selected amino acid substitutions in the C-terminal region of human immunodeficiency virus type 1 capsid protein affect virus assembly and release. However, these results were cell line-specific and Gag-Pol processing of P207A was not affected in 293T cells. 2004 The Journal of general virology Abstract HIV P207A 73 78 GagPol 51 58 15448352 Selected amino acid substitutions in the C-terminal region of human immunodeficiency virus type 1 capsid protein affect virus assembly and release. In HeLa-tat cells, no virus particles were detected with the P207A mutation, whereas the other mutant virus particles were heterogeneous in size and morphology. 2004 The Journal of general virology Abstract HIV P207A 61 66 Tat 8 11 15448352 Selected amino acid substitutions in the C-terminal region of human immunodeficiency virus type 1 capsid protein affect virus assembly and release. The two mutants P207A and V221G also had a profound effect on Gag-Pol protein processing in HeLa-tat cells. 2004 The Journal of general virology Abstract HIV P207A;V221G 16;26 21;31 GagPol;Tat 62;97 69;100 15451428 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease dimer complexed with acetyl pepstatin. In some of the virus isolates from patients undergoing heavy treatment with anti-HIV protease drugs, C95F mutation has appeared. 2004 Biochemical and biophysical research communications Abstract HIV C95F 101 105 PR 85 93 15451428 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease dimer complexed with acetyl pepstatin. The present study reports 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease dimer complexed with acetyl pepstatin. 2004 Biochemical and biophysical research communications Abstract HIV C1095F;C95M 55;50 61;54 PR 94 102 15451428 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease dimer complexed with acetyl pepstatin. These alterations may be relevant to C95F mutation conferring drug resistance to HIV-1 protease. 2004 Biochemical and biophysical research communications Abstract HIV C95F 37 41 PR 87 95 15452247 Diversity of human immunodeficiency virus type 1 subtype A and CRF03_AB protease in Eastern Europe: selection of the V77I variant and its rapid spread in injecting drug user populations. However, 13 of 23 (56.5%) subtype A isolates bore the V77I substitution known as the secondary protease mutation. 2004 Journal of virology Abstract HIV V77I 54 58 PR 95 103 15452247 Diversity of human immunodeficiency virus type 1 subtype A and CRF03_AB protease in Eastern Europe: selection of the V77I variant and its rapid spread in injecting drug user populations. Hybridization analysis showed that 55 of 115 (47.8%) HIV-1 isolates contained V77I, but this variant was not found in any of 31 DNA samples taken from regions, where the HIV-1 epidemic among IDUs started earlier 1997, as well as in any of four CRF03_AB isolates. 2004 Journal of virology Abstract HIV V77I 78 82 15452247 Diversity of human immunodeficiency virus type 1 subtype A and CRF03_AB protease in Eastern Europe: selection of the V77I variant and its rapid spread in injecting drug user populations. This finding demonstrates the transmission of the V77I mutant variant, which is spreading rapidly within the circulating viral pool in Russia and Kazakhstan. 2004 Journal of virology Abstract HIV V77I 50 54 15452247 Diversity of human immunodeficiency virus type 1 subtype A and CRF03_AB protease in Eastern Europe: selection of the V77I variant and its rapid spread in injecting drug user populations. V77I was associated with two synonymous substitutions in triplets 31 and 78, suggesting that all V77I-bearing viruses evolved from a single source in 1997. 2004 Journal of virology Abstract HIV V77I;V77I 97;0 101;4 15456247 A 4'-C-ethynyl-2',3'-dideoxynucleoside analogue highlights the role of the 3'-OH in anti-HIV active 4'-C-ethynyl-2'-deoxy nucleosides. The lipase-catalyzed resolution of rac-1h into ent-1h (beta-D-dideoxyribo) and ent-14 (beta-L-dideoxyribo) and the synthesis of the corresponding 5'-triphosphates established the stereochemical assignment based on HIV RT's preference for the beta-D-enantiomer, which was confirmed by assaying against the M184V variant, an RT mutant with a marked preference for incorporating nucleosides in the D-configuration. 2004 Journal of medicinal chemistry Abstract HIV M184V 305 310 RT;RT 218;323 220;325 15457680 Mutations and polymorphisms associated with antiretroviral drugs in HIV-1C-infected African patients. Appearance of the M184V mutation in the arm B patients coincided with a rebound of viral load (VL) (4.3 +/-0.1 log10 RNA copies/ml) and a significantly improved immunological parameter (deltaCD4=207.0+/-48.1 cells/microl; P<0.05). 2004 Antiviral chemistry & chemotherapy Abstract HIV M184V 18 23 15457680 Mutations and polymorphisms associated with antiretroviral drugs in HIV-1C-infected African patients. Interestingly, patients developing the M184V mutation preferentially harboured polymorphisms Q174K and/or I178L located in close proximity to pol position 184. 2004 Antiviral chemistry & chemotherapy Abstract HIV I178L;M184V;Q174K 106;39;93 111;44;98 Pol 142 145 15457680 Mutations and polymorphisms associated with antiretroviral drugs in HIV-1C-infected African patients. The M184V mutation occurred following a clear clinical benefit consisting of increased CD4 cell counts and lower plasma viral loads. 2004 Antiviral chemistry & chemotherapy Abstract HIV M184V 4 9 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. CONCLUSIONS: The data suggest that the presence of a G190A substitution attenuates the phenotypic resistance associated with a K103N substitution, although resistance is still present. 2004 Journal of clinical virology Abstract HIV G190A;K103N 53;127 58;132 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. G190A appears in 5-15% of the patients treated with nevirapine or efavirenz who develop clinical resistance. 2004 Journal of clinical virology Abstract HIV G190A 0 5 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. In the group with only K103N substitution, acquisition of resistance to all NNRTIs was observed. 2004 Journal of clinical virology Abstract HIV K103N 23 28 NNRTI 76 82 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. In the group with the double substitutions, G190A and K103N, delavirdine susceptibility decreased 13-fold, while resistance to nevirapine and efavirenz decreased by 239- and 154-folds, respectively (Kruskal-Wallis H P = 0.009). 2004 Journal of clinical virology Abstract HIV G190A;K103N 44;54 49;59 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. OBJECTIVES: In this study we investigated the effect of G190A and other NNRTI substitutions on the phenotypic susceptibility to this class of drugs. 2004 Journal of clinical virology Abstract HIV G190A 56 61 NNRTI 72 77 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. RESULTS: All isolates that developed only G190A substitution became less susceptible to nevirapine (median: 125-fold) and efavirenz (median: 10-fold) but were 2.5-fold more sensitive to delavirdine (Wilcoxon P = 0.06). 2004 Journal of clinical virology Abstract HIV G190A 42 47 15465412 Effects of the G190A substitution of HIV reverse transcriptase on phenotypic susceptibility of patient isolates to delavirdine. STUDY DESIGN: We identified 15 individuals, who after treatment with NNRTIs (nevirapine or efavirenz; median exposure of 20 months), developed isolated G190A, G190A in combination with K103N, or K103N alone. 2004 Journal of clinical virology Abstract HIV G190A;G190A;K103N;K103N 152;159;185;195 157;164;190;200 NNRTI 69 75 15465415 Impact of frequent natural polymorphisms at the protease gene on the in vitro susceptibility to protease inhibitors in HIV-1 non-B subtypes. The first virus, which had K20I, M36I and V82I, showed 2.9-fold decreased susceptibility to APV, while the second virus showed 3.9-fold decreased susceptibility to both NFV and RTV, with amino acid substitutions K20I, M36I, L63P and V82I. 2004 Journal of clinical virology Abstract HIV K20I;K20I;L63P;M36I;M36I;V82I;V82I 27;212;224;33;218;42;233 31;216;228;37;222;46;237 15465813 Requirements for DNA unpairing during displacement synthesis by HIV-1 reverse transcriptase. The F61W mutant form of HIV-1 reverse transcriptase, which is partially impaired for displacement synthesis, exhibits a reduction in the amount of melting at the +1 and +2 positions. 2004 The Journal of biological chemistry Abstract HIV F61W 4 8 RT 30 51 15472857 Genotypic resistance in HIV-1-infected patients with persistently detectable low-level viremia while receiving highly active antiretroviral therapy. The most common mutations were M184V, K65R, and M41L/T215Y. 2004 Clinical infectious diseases Abstract HIV K65R;M184V;M41L;T215Y 38;31;48;53 42;36;52;58 15479797 Evaluation of the functional involvement of human immunodeficiency virus type 1 integrase in nuclear import of viral cDNA during acute infection. During acute infection, some mutations (N144Q, PYNP>KL, and KKK>AAA) severely reduced viral gene expression to less than 1% the wild-type (WT) level. 2004 Journal of virology Abstract HIV N144Q 40 45 15479797 Evaluation of the functional involvement of human immunodeficiency virus type 1 integrase in nuclear import of viral cDNA during acute infection. Further analysis revealed that IN proteins carrying the N144Q, PYNP>KL, and KKK>AAA mutations showed severely reduced binding to viral cDNA but kept their karyophilic properties. 2004 Journal of virology Abstract HIV N144Q 56 61 IN 31 33 15479797 Evaluation of the functional involvement of human immunodeficiency virus type 1 integrase in nuclear import of viral cDNA during acute infection. Meanwhile, the levels of integrated viral cDNA produced by N144Q, PYNP>KL, and KKK>AAA mutants were severely reduced to less than 1% the WT level. 2004 Journal of virology Abstract HIV N144Q 59 64 15479823 Influence of gag on human immunodeficiency virus type 1 species-specific tropism. We also show that sensitivity to restriction is controlled by an H87Q mutation in the capsid, implicated in the immune control of HIV-1, possibly linking immune and innate control of HIV-1 infection. 2004 Journal of virology Abstract HIV H87Q 65 69 Capsid 86 92 HIV infections 183 198 15479840 Structural and thermodynamic basis for the binding of TMC114, a next-generation human immunodeficiency virus type 1 protease inhibitor. To examine the basis for this potency, we solved crystal structures of TMC114 complexed with wt HIV-1 protease and TMC114 and APV complexed with an MDR (L63P, V82T, and I84V) protease variant. 2004 Journal of virology Abstract HIV I84V;L63P;V82T 169;153;159 173;157;163 PR;PR 102;175 110;183 15481987 4-benzyl- and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones, a new family of potent anti-HIV agents: optimization and in vitro evaluation against clinically important HIV mutant strains. Thirty-three compounds displayed nanomolar range activity in vitro against wild-type HIV-1, and among these, 18 were active against the 103N, Y181C, and Y188L mutant strains with IC50 values inferior to 1 microM. 2004 Journal of medicinal chemistry Abstract HIV Y181C;Y188L 142;153 147;158 15482137 Atazanavir: improving the HIV protease inhibitor class. Atazanavir selects for the I50L mutation in HIV protease that confers increased susceptibility to other protease inhibitors in vitro. 2003 Expert review of anti-infective therapy Abstract HIV I50L 27 31 PR;PR 48;104 56;112 15482179 The impact of the M184V substitution on drug resistance and viral fitness. However, it is thought that lamivudine may still contribute to the effectiveness of antiretroviral therapy, even after the appearance of the M184V mutation. 2004 Expert review of anti-infective therapy Abstract HIV M184V 141 146 15482179 The impact of the M184V substitution on drug resistance and viral fitness. M184V also has a positive effect on HIV-1 RT fidelity, reducing spontaneous HIV mutagenesis. 2004 Expert review of anti-infective therapy Abstract HIV M184V 0 5 RT 42 44 15482179 The impact of the M184V substitution on drug resistance and viral fitness. M184V may affect sensitivity to other drugs, such as zidovudine (Retrovir, GlaxoSmithKline), in HIV-1 variants that already contain resistance mutations to zidovudine, during concomitant treatment with lamivudine. 2004 Expert review of anti-infective therapy Abstract HIV M184V 0 5 15482179 The impact of the M184V substitution on drug resistance and viral fitness. Processivity of the reverse transcriptase enzyme may be affected by mutations such as M184V, and this may be a major determinant of viral replication fitness. 2004 Expert review of anti-infective therapy Abstract HIV M184V 86 91 RT 20 41 15482179 The impact of the M184V substitution on drug resistance and viral fitness. This is also true of certain specific mutations, such as M184V in the reverse transcriptase enzyme, resulting in resistance to the nucleoside analog, lamivudine (Epivir, GlaxoSmithKline). 2004 Expert review of anti-infective therapy Abstract HIV M184V 57 62 RT 70 91 15482202 Nevirapine in the treatment of HIV. Nevirapine-resistant mutations are common to the non-nucleoside reverse transcriptase inhibitor family and they include K103N, V106A, Y181C, Y188C and G190A. 2004 Expert review of anti-infective therapy Abstract HIV G190A;K103N;V106A;Y181C;Y188C 151;120;127;134;141 156;125;132;139;146 NNRTI 49 85 15483463 Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. Development of K65R was associated with mostly low-level changes in phenotypic susceptibility to tenofovir DF and other nucleoside reverse transcriptase inhibitors and was not associated with viral load rebound. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 15 19 NRTI 120 152 15483463 Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. Other than K65R, the patterns of mutations that developed were not significantly different between the tenofovir DF and placebo control arms, suggesting that the background therapies caused their development. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 11 15 15483463 Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. The K65R mutation emerged only in patients with no detectable TAMs at baseline, whereas new TAMs developed similarly between patients with or without TAMs at baseline. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 4 8 15483463 Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. The K65R mutation, which occurred in 8 patients (3%), was the only emergent mutation directly associated with tenofovir DF therapy. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 4 8 15483463 Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. Therefore, intensification with once-daily tenofovir DF therapy resulted in a sustained reduction in HIV-1 viral load and a low risk for development of the K65R mutation in this treatment-experienced patient population. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 156 160 15491611 Conserved residues in the HIV-1 Nef hydrophobic pocket are essential for recruitment and activation of the Hck tyrosine kinase. Hck activation increased further by substitution of ELI Glu83 with Ala and Asn116 with His, suggestive of a supportive role for these residues in Hck binding. 2004 Journal of molecular biology Abstract HIV E83A;N116H 56;75 70;90 15491611 Conserved residues in the HIV-1 Nef hydrophobic pocket are essential for recruitment and activation of the Hck tyrosine kinase. In a complementary experiment, substitution of ELI Ile120 with Tyr partly restored ELI Nef-induced Hck activation and transformation in Rat-2 cells. 2004 Journal of molecular biology Abstract HIV I120Y 51 66 Nef 87 90 15491611 Conserved residues in the HIV-1 Nef hydrophobic pocket are essential for recruitment and activation of the Hck tyrosine kinase. Substitution of SF2 Nef Tyr120 with Ile completely abolished Hck recruitment and activation. 2004 Journal of molecular biology Abstract HIV Y120I 24 39 Nef 20 23 15504840 Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. However, the relative effectiveness of nucleoside RT inhibitors that are structurally unrelated to 3TC in selecting and/or maintaining M184V has not been investigated. 2004 Antimicrobial agents and chemotherapy Abstract HIV M184V 135 140 RT 50 52 15504840 Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. In contrast, neither ddI nor ddC was able to maintain M184V to the same extent as the other drugs after 10 weeks of tissue culture in mixtures of wild-type viruses and isolates containing M184V in different proportions. 2004 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V 54;188 59;193 15504840 Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. In the present study, we have studied the abilities of a variety of drugs, i.e., zalcitabine (ddC), didanosine (ddI), abacavir (ABC), and the novel nucleoside SPD754, in addition to 3TC, to maintain the presence of M184V in tissue culture and have shown that SPD754, ABC, and 3TC are able to preserve M184V in mixed dual infections consisting of wild-type viruses and clinical isolates which contained the M184V mutation. 2004 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V;M184V 215;301;406 220;306;411 15504840 Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. M184V is also associated with several alterations of RT enzymatic function in vitro that may adversely affect viral fitness or replication capacity, which creates a potential rationale for its maintenance once it has been selected by antiviral chemotherapy. 2004 Antimicrobial agents and chemotherapy Abstract HIV M184V 0 5 RT 53 55 15504840 Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. Moreover, M184V could also be maintained in these cultures when a subtherapeutic concentration of 3TC (i.e., 0.05 microM) was used. 2004 Antimicrobial agents and chemotherapy Abstract HIV M184V 10 15 15504840 Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase (RT) is rapidly selected in tissue culture following serial passage of wild-type virus in the presence of increasing concentrations of lamivudine (3TC). 2004 Antimicrobial agents and chemotherapy Abstract HIV M184V 4 9 RT;RT 62;85 83;87 15504868 In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase inhibitors mycophenolic acid and ribavirin demonstrates potent activity against wild-type and drug-resistant variants of human immunodeficiency virus type 1. Similarly, when tested against a mutant virus fully resistant to inhibition by DAPD (K65R/Q151M), MPA and RBV reduced the EC(50) for DAPD to within twofold of that for the wild type. 2004 Antimicrobial agents and chemotherapy Abstract HIV K65R;Q151M 85;90 89;95 15507631 Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. AlaP2 does not fill the P2 pocket completely; PheP1' makes van der Waals interactions with Val82 that are lost with the V82A protease mutation. 2004 Journal of virology Abstract HIV V82A 120 124 PR 125 133 15507631 Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. In response to the V82A drug-resistant protease mutation, the P2 alanine of NC-p1 mutates to valine (AP2V). 2004 Journal of virology Abstract HIV V82A 19 23 PR;NC 39;76 47;78 15507631 Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. To provide a structural rationale for HIV-1 protease binding to the NC-p1 cleavage site, we solved the crystal structures of inactive (D25N) WT and V82A HIV-1 proteases in complex with their respective WT and AP2V mutant NC-p1 substrates. 2004 Journal of virology Abstract HIV D25N;V82A 135;148 139;152 PR;PR;NC;NC 44;159;68;221 52;168;70;223 15530994 Nonnucleoside HIV-1 reverse transcriptase inhibitors; part 3. Synthesis and antiviral activity of 5-alkyl-2-[(aryl and alkyloxyl-carbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3H)-ones. The most active compound, 5-isopropyl-2-[(4'-methoxyphenylcarbonyl-methyl)thio]-6-(1-naphthylmethyl)pyrimidin-4(3H)-one showed activity against HIV-1 and against the double mutated strain of HIV(Y181C and K103N) in the micromolar range. 2004 Bioorganic chemistry Abstract HIV K103N;Y181C 205;195 210;201 15533307 The interactions of the HIV gp41 fusion peptides with zwitterionic membrane mimics determined by NMR spectroscopy. Pulsed field-gradient diffusion measurements in DPC and in 4:1 DPC/sodium dodecylsulfate mixed micelles showed that there is no major difference between the partition coefficients of the fusogenic wt peptide and the V2E mutant in these micelles, indicating that there is no correlation between the activity of the fusion peptides and their membrane affinities. 2004 Biochimica et biophysica acta Abstract HIV V2E 216 219 15533307 The interactions of the HIV gp41 fusion peptides with zwitterionic membrane mimics determined by NMR spectroscopy. The spin-label studies, utilizing spin labels 5- and 16-doxystearic acids in the DPC micelles, provided clear indication that the wt FP inserts its N-terminus into the micelles while the V2E mutant does not insert into the micelles. 2004 Biochimica et biophysica acta Abstract HIV V2E 187 190 15533307 The interactions of the HIV gp41 fusion peptides with zwitterionic membrane mimics determined by NMR spectroscopy. The wild-type (wt) N-terminal 23-residue fusion peptide (FP) of the human immunodeficiency virus (HIV) fusion protein gp41 and its V2E mutant have been studied by nuclear magnetic resonance (NMR) spectroscopy in dodecylphosphocholine (DPC) micelles as membrane mimics. 2004 Biochimica et biophysica acta Abstract HIV V2E 131 134 gp41 118 122 15537346 Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 1. Members of this quinolone series retain high activity against the important resistance mutations in RT at Tyr181Cys and Leu100Ile. 2004 Journal of medicinal chemistry Abstract HIV L100I;Y181C 120;106 129;115 RT 100 102 15537645 Analysis of HIV-1 viral infectivity factor-mediated proteasome-dependent depletion of APOBEC3G: correlating function and subcellular localization. Finally mutations at Vif Ile(9) disrupted the ability of Vif or Vif(C114S) to coimmunoprecipitate and to co-localize with APOBEC3G, suggesting that the N terminus of Vif mediates interactions with APOBEC3G. 2005 The Journal of biological chemistry Abstract HIV C114S 68 73 Vif;Vif;Vif;Vif 21;57;64;166 24;60;67;169 15537645 Analysis of HIV-1 viral infectivity factor-mediated proteasome-dependent depletion of APOBEC3G: correlating function and subcellular localization. On the contrary, Vif(C114S), which is inactive but continues to interact with APOBEC3G, stably associated with APOBEC3G in the cytoplasm, resulting in complete co-localization at cytoplasmic bodies and a dose-dependent exclusion of Vif(C114S) from the nucleus. 2005 The Journal of biological chemistry Abstract HIV C114S;C114S 21;236 26;241 Vif;Vif 17;232 20;235 15542562 Insights into saquinavir resistance in the G48V HIV-1 protease: quantum calculations and molecular dynamic simulations. Molecular dynamics simulations of the wild-type and the G48V HIV-1 protease complexed with saquinavir were carried out to explore structure and interactions of the drug resistance. 2005 Biophysical journal Abstract HIV G48V 56 60 PR 67 75 15542562 Insights into saquinavir resistance in the G48V HIV-1 protease: quantum calculations and molecular dynamic simulations. The G48V is considered the key signature residue mutation of HIV-1 protease developing with saquinavir therapy. 2005 Biophysical journal Abstract HIV G48V 4 8 PR 67 75 15542626 Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication. HIV-1(C130G) was also defective for reverse transcription, but Vpr-integrase(C130G) did not efficiently complement class I mutant HIV-1. 2004 Journal of virology Abstract HIV C130G;C130G 6;77 11;82 RT;IN;Vpr 36;67;63 57;76;66 15542626 Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication. Previous work established HIV-1(K186Q), HIV-1(Q214L/Q216L), and HIV-1(C130G) as replication defective, but phenotypic classification was unclear and nuclear import in nondividing cells was not addressed. 2004 Journal of virology Abstract HIV Q214L;Q216L;C130G;K186Q 46;52;70;32 51;57;75;37 15542626 Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication. Since HIV-1(C130A) grew like the wild type, we conclude that Cys-130 is not essential for replication and speculate that perturbation of integrase structure contributed to the pleiotropic HIV-1(C130G) phenotype. 2004 Journal of virology Abstract HIV C130A;C130G 12;194 17;199 IN 137 146 15542626 Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication. These mutants as well as HIV-1(V165A) synthesized reduced cDNA levels, but a normal fraction of mutant cDNA localized to dividing and nondividing cell nuclei. 2004 Journal of virology Abstract HIV V165A 31 36 15542626 Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication. We previously determined that HIV-1(V165A), originally reported as defective for nuclear import, was a class II mutant. 2004 Journal of virology Abstract HIV V165A 36 41 15544690 Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens. M184V was the most frequently selected mutation by ABC alone (24 of 70 patients) and by ABC plus 3TC (48 of 70 patients). 2004 HIV medicine Abstract HIV M184V 0 5 15544690 Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens. OBJECTIVES: Abacavir (ABC) selects for four mutations (K65R, L74V, Y115F and M184V) in HIV-1 reverse transcriptase (RT), both in vitro and during monotherapy in vivo. 2004 HIV medicine Abstract HIV K65R;L74V;M184V;Y115F 55;61;77;67 59;65;82;72 RT;RT 93;116 114;118 15544690 Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens. RESULTS: K65R was selected infrequently by ABC-containing regimens in the absence of ZDV (13 of 127 patients), while L74V/I was selected more frequently (51 of 127 patients). 2004 HIV medicine Abstract HIV K65R;L74I;L74V 9;117;117 13;123;123 15544690 Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens. Selection of both K65R and L74V/I was significantly reduced by co-administration of ZDV with ABC (one of 86 and two of 86 patients, respectively). 2004 HIV medicine Abstract HIV K65R;L74I;L74V 18;27;27 22;33;33 15544690 Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens. The K65R mutation conferred the broadest phenotypic cross-resistance of the mutations studied. 2004 HIV medicine Abstract HIV K65R 4 8 15544690 Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens. Y115F was uncommon in the absence (seven of 127 patients) or presence (four of 86 patients) of ZDV. 2004 HIV medicine Abstract HIV Y115F 0 5 15545865 Alternative, age- and viral load-related routes of nelfinavir resistance in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy. The prevalence of L90M was similar to that of D30N. 2004 The Pediatric infectious disease journal Abstract HIV D30N;L90M 46;18 50;22 15545865 Alternative, age- and viral load-related routes of nelfinavir resistance in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy. There was a significant correlation with a higher viral load and lower age and the occurrence of L90M. 2004 The Pediatric infectious disease journal Abstract HIV L90M 97 101 15548134 Nucleotide specificity of HIV-1 reverse transcriptases with amino acid substitutions affecting Ala-114. Discrimination between AZTTP (3'-azido-3'-deoxythymidine triphosphate) and dTTP was not significantly affected by mutations A114S and A114G in assays carried out with heteropolymeric template/primers. 2005 The Biochemical journal Abstract HIV A114G;A114S 134;124 139;129 15548134 Nucleotide specificity of HIV-1 reverse transcriptases with amino acid substitutions affecting Ala-114. Four mutant RTs having serine, glycine, threonine or valine instead of Ala-114 were obtained by site-directed mutagenesis. 2005 The Biochemical journal Abstract HIV A114S;A114T;A114G;A114V 23;23;23;23 78;78;78;78 RT 12 15 15548134 Nucleotide specificity of HIV-1 reverse transcriptases with amino acid substitutions affecting Ala-114. In contrast, A114S and A114V showed wild-type ddNTP/dNTP discrimination efficiencies. 2005 The Biochemical journal Abstract HIV A114S;A114V 13;23 18;28 15548134 Nucleotide specificity of HIV-1 reverse transcriptases with amino acid substitutions affecting Ala-114. Steady-state kinetic analysis of the incorporation of ddNTPs compared with dNTPs showed that substituting glycine for Ala-114 produced a 5-6-fold increase in the RT's ability to discriminate against ddNTPs (including the physiologically relevant metabolites of zalcitabine and didanosine), a result that was confirmed in primer-extension assays. 2005 The Biochemical journal Abstract HIV A114G 106 125 RT 162 164 15548134 Nucleotide specificity of HIV-1 reverse transcriptases with amino acid substitutions affecting Ala-114. While mutants A114S and A114G retained significant DNA polymerase activity, A114T and A114V showed very low catalytic efficiency in nucleotide incorporation assays, due to their high apparent K(m) values for dNTP. 2005 The Biochemical journal Abstract HIV A114G;A114S;A114T;A114V 24;14;76;86 29;19;81;91 Pol 55 65 15550379 Mechanistic insights into the suppression of drug resistance by human immunodeficiency virus type 1 reverse transcriptase using alpha-boranophosphate nucleoside analogs. Here, we extend this property to BH3-d4TTP and BH3-3TCTP toward their clinically relevant mutants Q151M and M184V, respectively. 2005 The Journal of biological chemistry Abstract HIV M184V;Q151M 108;98 113;103 15550379 Mechanistic insights into the suppression of drug resistance by human immunodeficiency virus type 1 reverse transcriptase using alpha-boranophosphate nucleoside analogs. Indeed, the approximately 100-fold decrease in polymerase activity caused by the R72A substitution is restored to wild-type levels using BH3-dTTP. 2005 The Journal of biological chemistry Abstract HIV R72A 81 85 Pol 47 57 15550379 Mechanistic insights into the suppression of drug resistance by human immunodeficiency virus type 1 reverse transcriptase using alpha-boranophosphate nucleoside analogs. Likewise, resistance to 3TCTP by M184V RT (30-fold) and K65R/M184V RT (180-fold) is suppressed using BH3-3TCTP because of a 160-fold acceleration of the catalytic constant kpol. 2005 The Journal of biological chemistry Abstract HIV K65R;M184V;M184V 56;61;33 60;66;38 RT;RT 39;67 41;69 15550379 Mechanistic insights into the suppression of drug resistance by human immunodeficiency virus type 1 reverse transcriptase using alpha-boranophosphate nucleoside analogs. Pre-steady-state kinetics on mutants of the Q151M RT family reveal a 3-5-fold resistance to d4TTP. 2005 The Journal of biological chemistry Abstract HIV Q151M 44 49 RT 50 52 15550379 Mechanistic insights into the suppression of drug resistance by human immunodeficiency virus type 1 reverse transcriptase using alpha-boranophosphate nucleoside analogs. We have shown previously that alpha-boranophosphate nucleoside analogs suppress RT-mediated resistance when the catalytic rate is responsible for drug resistance such as in the case of K65R and dideoxy (dd)NTPs, and Q151M toward AZTTP and ddNTPs. 2005 The Journal of biological chemistry Abstract HIV K65R;Q151M 185;216 189;221 RT 80 82 15553926 HIV-1 reverse transcriptase variants: molecular modeling of Y181C, V106A, L100I, and K103N mutations with nonnucleoside inhibitors using Monte Carlo simulations in combination with a linear response method. The energies and physical descriptors for the binding of 21 novel 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazole (BPBI) analogs to HIV-1 reverse transcriptase (RT) variants Y181C, L100I, V106A, and K103N have been determined using Monte Carlo (MC) simulations. 2003 Drug design and discovery Abstract HIV K103N;L100I;V106A;Y181C 211;193;200;186 216;198;205;191 RT;RT 150;173 171;175 15561833 Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replication. In in vitro inhibition assays, expression and purification of the recombinant Gln145Met HIV-1 RT revealed a strong loss of catalytic efficiency of the mutated enzyme, as well as significant resistance to both zidovudine and efavirenz. 2004 Antimicrobial agents and chemotherapy Abstract HIV Q145M 78 87 RT 94 96 15561833 Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replication. Lower levels of replication of the Gln145Met recombinant strain compared with those of both Gln151Met and wild-type recombinant strains were observed. 2004 Antimicrobial agents and chemotherapy Abstract HIV Q145M;Q151M 35;92 44;101 15561833 Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replication. Several amino acid substitutions different from the recently reported Gln145Met change (S. 2004 Antimicrobial agents and chemotherapy Abstract HIV Q145M 70 79 15561833 Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replication. This finding may explain the lower frequency of Gln145Met/Leu mutations observed compared with the frequencies of Gln151Met/Leu mutations and the insertion at position 69 in HAART-experienced patients. 2004 Antimicrobial agents and chemotherapy Abstract HIV Q145L;Q145M;Q151L;Q151M 48;48;114;114 61;61;127;127 15561844 TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. In an initial screen for activity against a panel of 25 viruses carrying single and double reverse transcriptase amino acid substitutions associated with NNRTI resistance, the EC50 of TMC125 was <5 nM for 19 viruses, including the double mutants K101E+K103N and K103N+Y181C. 2004 Antimicrobial agents and chemotherapy Abstract HIV K101E;K103N;K103N;Y181C 246;252;262;268 251;257;267;273 RT;NNRTI 91;154 112;159 15561845 Clinically relevant interpretation of genotype and relationship to plasma drug concentrations for resistance to saquinavir-ritonavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients. Adjusted in a multivariate analysis, taking into account all the confounding factors, such as the nucleoside used, five mutations were combined in a resistance score associated with a reduced virological response to an SQV-plus-RTV regimen: L24I, I62V, V82A/F/T/S, I84V, and L90IM. 2004 Antimicrobial agents and chemotherapy Abstract HIV I62V;I84V;L24I;L90I;L90M;V82A;V82F;V82S;V82T 247;265;241;275;275;253;253;253;253 251;269;245;280;280;263;263;263;263 15561868 Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. In combination with other drug resistance mutations, L23I was associated with multidrug resistance and a compensatory increase in replication capacity. 2004 Antimicrobial agents and chemotherapy Abstract HIV L23I 53 57 15561868 Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. In combination with V82I, L23I was associated with a sevenfold reduction in nelfinavir susceptibility and a decrease in replication capacity. 2004 Antimicrobial agents and chemotherapy Abstract HIV L23I;V82I 26;20 30;24 15561868 Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. We observed a previously uncharacterized mutation in the protease substrate cleft, L23I, in 31 of 4,303 persons undergoing human immunodeficiency virus type 1 genotypic resistance testing. 2004 Antimicrobial agents and chemotherapy Abstract HIV L23I 83 87 PR 57 65 15563158 Understanding the basis of resistance in the irksome Lys103Asn HIV-1 reverse transcriptase mutant through targeted molecular dynamics simulations. Results of targeted molecular dynamics simulations confirm the existence of a higher energy barrier for creation of the pocket where non-nucleoside reverse transcriptase inhibitors bind in the K103N mutant enzyme relative to wild-type. 2004 Journal of the American Chemical Society Abstract HIV K103N 193 198 NNRTI 133 169 15564466 In vitro characterization of a simian immunodeficiency virus-human immunodeficiency virus (HIV) chimera expressing HIV type 1 reverse transcriptase to study antiviral resistance in pigtail macaques. Two simian-human immunodeficiency viruses (SHIVs) were derived from the genetic background of SIV(mne): SIV-RT-YY contains RT substitutions intended to confer NNRTI susceptibility (V181Y and L188Y), and RT-SHIV(mne) contains the entire HIV-1 RT coding region. 2004 Journal of virology Abstract HIV L188Y;V181Y 191;181 196;187 NNRTI;RT;RT;RT;RT 159;108;123;203;242 164;110;125;205;244 15569685 Structural and dynamics studies of the D54A mutant of human T cell leukemia virus-1 capsid protein. NMR (15)N relaxation data were used to characterize the backbone dynamics of the D54A mutant in the context of the N-terminal domains, compared with the wild-type counterpart. 2005 The Journal of biological chemistry Abstract HIV D54A 81 85 15572008 Performance of drug-resistance genotypic assays among HIV-1 infected patients with predominantly CRF02_AG strains of HIV-1 in Abidjan, Cote d'Ivoire. All 19 (100%) samples that had the K70R/E mutation detected by VircoGEN were detected by ViroSEQ, and 18 (94.7%) by TrueGene. 2005 Journal of clinical virology Abstract HIV K70E;K70R 35;35 41;41 15572008 Performance of drug-resistance genotypic assays among HIV-1 infected patients with predominantly CRF02_AG strains of HIV-1 in Abidjan, Cote d'Ivoire. All ten samples with the M184V mutation, three with the K65R, two with the G190A mutation, one with the K103N mutation, and one with the V75T mutation were detected similarly by all three assays. 2005 Journal of clinical virology Abstract HIV G190A;K103N;K65R;M184V;V75T 75;104;56;25;137 80;109;60;30;141 15572008 Performance of drug-resistance genotypic assays among HIV-1 infected patients with predominantly CRF02_AG strains of HIV-1 in Abidjan, Cote d'Ivoire. For the protease gene, all three assays detected the I84V (n = 1), M46I (n = 1), and L90M (n = 1) mutations. 2005 Journal of clinical virology Abstract HIV I84V;L90M;M46I 53;85;67 57;89;71 PR 8 16 15572008 Performance of drug-resistance genotypic assays among HIV-1 infected patients with predominantly CRF02_AG strains of HIV-1 in Abidjan, Cote d'Ivoire. RESULTS: For the reverse transcriptase gene, all 27 samples that had the T215Y/F mutation were detected by VircoGEN , ViroSEQ, and TrueGene. 2005 Journal of clinical virology Abstract HIV T215F;T215Y 73;73 80;80 RT 17 38 15577410 Long-term persistence of primary genotypic resistance after HIV-1 seroconversion. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K219Q;Y181C 23;13 28;18 RT 32 34 15577410 Long-term persistence of primary genotypic resistance after HIV-1 seroconversion. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;M41L;T69N 27;15;21 32;19;25 RT;RT 59;82 80;84 15577421 Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. It was also observed that individuals in the PT subgroups who harbored RT mutations or PRAMs with M184V had lower levels of plasma viremia than individuals who lacked M184V (P < 0.05). 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;M184V 98;167 103;172 RT 71 73 15577421 Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. There was a decreased prevalence in the PHI population of resistant viruses co-expressing NNMs or TAMs with M184V compared with viruses that harbored NNMs or TAMs in the absence of M184V (P < 0.0001). 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;M184V 108;181 113;186 HIV infections 40 43 15577421 Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. These findings suggest that both decreased viremia and viral fitness in the case of M184V-containing HIV-1 variants may impact on viral transmissibility. 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 84 89 15577421 Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. This study compared the incidence of HIV-1 variants harboring mutations conferring resistance to thymidine analogues, ie, thymidine analogue mutations (TAMs), nonnucleoside reverse transcriptase (RT) inhibitors (NNMs), lamivudine (3TC) (ie, M184V), and protease inhibitors (PIs) acquired in primary HIV infection (PHI) (n = 59) to their observed prevalence in a corresponding potential transmitter (PT) population of persons harboring resistant infections (n = 380). 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 241 246 NNRTI;PR;PI;RT 159;253;274;196 194;261;277;198 HIV infections;HIV infections 291;314 312;317 15577421 Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. Whereas the frequencies of observed TAMs, NNMs, M184V, and protease-associated mutations (PRAMs) were similar in the PT groups, the prevalence of M184V and major PI mutations were significantly lower in the PHI group (PHI/PT ratios of 0.14 and 0.39, respectively). 2004 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;M184V 48;146 53;151 PR;PI 59;162 67;164 HIV infections;HIV infections 207;218 210;221 15577623 Multiple mutations in human immunodeficiency virus-1 integrase confer resistance to the clinical trial drug S-1360. They included T66I and L74M that have both been associated with resistance against the diketo acid L-708,906. 2004 AIDS (London, England) Abstract HIV L74M;T66I 23;14 27;18 15577635 Predictors of selection of K65R: tenofovir use and lack of thymidine analogue mutations. None out of 216 drug-naive subjects showed K65R. 2004 AIDS (London, England) Abstract HIV K65R 43 47 15577635 Predictors of selection of K65R: tenofovir use and lack of thymidine analogue mutations. The rate of K65R increased from 0.6% in 1999 to 11.5% in 2004. 2004 AIDS (London, England) Abstract HIV K65R 12 16 15577635 Predictors of selection of K65R: tenofovir use and lack of thymidine analogue mutations. The recognition of K65R correlated negatively with the presence of thymidine analogue mutations but positively with Q151M. 2004 AIDS (London, England) Abstract HIV K65R;Q151M 19;116 23;121 15578977 Structure and function of HIV-1 auxiliary regulatory protein Vpr: novel clues to drug design. Recent evidence suggests that Vpr interacts with a cellular ubiquitination machinery and promotes degradation of Vpr mutants carrying the L64P mutation. 2004 Current drug targets. Immune, endocrine and metabolic disorders Abstract HIV L64P 138 142 Vpr;Vpr 30;113 33;116 15578977 Structure and function of HIV-1 auxiliary regulatory protein Vpr: novel clues to drug design. The pro-apoptotic activity of Vpr is dependent on the subtype of the HIV-1 isolate, and may be dramatically enhanced by a single L64P mutation. 2004 Current drug targets. Immune, endocrine and metabolic disorders Abstract HIV L64P 129 133 Vpr 30 33 15585093 Molecular characterization of HIV type 1 isolates from untreated patients of Mumbai (Bombay), India, and detection of rare resistance mutations. Two isolates showed M184V substitution the reverse transcriptase indicating resistance to 3TC. 2004 AIDS research and human retroviruses Abstract HIV M184V 20 25 RT 43 64 15588338 Human immunodeficiency virus type 1 infection in Oman: antiretroviral therapy and frequencies of drug resistance mutations. The genotypes of 17 other patients carried one or two RTI mutations, mainly the lamivudine-associated resistance mutation M184V. 2004 AIDS research and human retroviruses Abstract HIV M184V 122 127 RT 54 57 15588834 Electrostatic repulsion, compensatory mutations, and long-range non-additive effects at the dimerization interface of the HIV capsid protein. (ii) The mutation Glu180 to Ala was detected in nearly all type 2 human immunodeficiency virus variants, and in several simian immunodeficiency viruses analyzed. 2005 Journal of molecular biology Abstract HIV E180A 18 31 15588834 Electrostatic repulsion, compensatory mutations, and long-range non-additive effects at the dimerization interface of the HIV capsid protein. (iii) The increase in the affinity constant caused by the multiple mutation to Ala of Ser178, Glu180, Glu187 and Gln192 was more than one order of magnitude lower than predicted if additivity were present, despite the fact that the 178/180 pair and the two other residues were located more than 10A apart. 2005 Journal of molecular biology Abstract HIV S178A 79 92 15588834 Electrostatic repulsion, compensatory mutations, and long-range non-additive effects at the dimerization interface of the HIV capsid protein. However, this mutation was strictly co-variant with mutations Ser178Asp in a neighboring residue, and Glu187Gln. 2005 Journal of molecular biology Abstract HIV E187Q;S178D 102;62 111;71 15588834 Electrostatic repulsion, compensatory mutations, and long-range non-additive effects at the dimerization interface of the HIV capsid protein. In previous studies, thermodynamic dissection of the dimerization interface in CA-C, the C-terminal domain of the capsid protein of human immunodeficiency virus type 1, revealed that individual mutation to alanine of Ser178, Glu180, Glu187 or Gln192 led to significant increases in dimerization affinity. 2005 Journal of molecular biology Abstract HIV S178A 206 223 Capsid;Capsid 114;79 120;81 15588834 Electrostatic repulsion, compensatory mutations, and long-range non-additive effects at the dimerization interface of the HIV capsid protein. Thermodynamic analysis of multiple mutants showed that Ser178Asp compensated, alone or together with Glu187Gln, the increase in affinity caused by the mutation Glu180Ala, and restored a lower dimerization affinity. 2005 Journal of molecular biology Abstract HIV E180A;E187Q;S178D 160;101;55 169;110;64 15596835 Mutations in the RNase H primer grip domain of murine leukemia virus reverse transcriptase decrease efficiency and accuracy of plus-strand DNA transfer. Using either beta-galactosidase (lacZ) or green fluorescent protein (GFP) reporter genes, we found that S557A, A558V, and Q559L substitutions resulted in statistically significant increases in viral mutation rates, ranging from 2.1- to 3.8-fold. 2005 Journal of virology Abstract HIV A558V;Q559L;S557A 111;122;104 116;127;109 15596835 Mutations in the RNase H primer grip domain of murine leukemia virus reverse transcriptase decrease efficiency and accuracy of plus-strand DNA transfer. We previously showed that a Y586F substitution in the MLV RNase H primer grip resulted in a 17-fold increase in substitutions within 18 nucleotides of adenine-thymine tracts, which are associated with a bent DNA conformation. 2005 Journal of virology Abstract HIV Y586F 28 33 15608517 Characterization of mutations in CRF01_AE virus isolates from antiretroviral treatment-naive and -experienced patients in Singapore. There were differences between CRF01_AE and subtype B viruses in several drug resistance mutations including the following: D67N, L210F, K101E, V106M, V179I/D, G190A/S/E, and G48V (which were more common in CRF01_AE virus) and M41L, T215Y, and V82A (which were less common in CRF01_AE virus). 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D67N;G190A;G190E;G190S;G48V;K101E;L210F;M41L;T215Y;V106M;V179D;V179I;V82A 124;160;160;160;175;137;130;227;233;144;151;151;244 128;169;169;169;179;142;135;231;238;149;158;158;248 15608522 Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. Both patients with detectable K103N mutations who received efavirenz failed treatment, and virus expressing K103N emerged. 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;K103N 30;108 35;113 15608522 Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. Four of 5 patients without detectable K103N mutations also failed efavirenz, associated with the emergence of nonnucleoside reverse transcriptase mutations that included K103N in 2 cases. 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;K103N 38;170 43;175 NNRTI 110 145 15608522 Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. The emergence of a minority viral population expressing K103N was identified in 1 patient from a separate study group subsequent to discontinuing treatment with nevirapine. 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 56 61 15608522 Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. The presence of minority viral populations expressing efavirenz cross-resistance could explain these observations, and such populations were sought in plasma from patients failing nevirapine for whom genotyping revealed the presence of the Y181C mutation (usually associated with limited efavirenz cross-resistance) but not the K103N mutation (which produces high-level efavirenz resistance). 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;Y181C 328;240 333;245 15608522 Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. Viral populations expressing K103N (>1% total virus) were detected by sequence-selective polymerase chain reaction in 4 of 16 patients failing nevirapine, although, in retrospect, the mutation was not perceptible in the original genotype in only 2 cases. 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 29 34 Pol 89 99 15611041 HIV-1 Tat interactions with p300 and PCAF transcriptional coactivators inhibit histone acetylation and neurotrophin signaling through CREB. A Tat mutant, TatK28A/K50A, defective for binding p300 and PCAF, neither repressed NGF-responsive CRE transactivation nor inhibited histone acetylation. 2005 The Journal of biological chemistry Abstract HIV K50A 22 26 Tat;Tat 2;14 5;17 15613304 Mutations conferring resistance to human immunodeficiency virus type 1 fusion inhibitors are restricted by gp41 and Rev-responsive element functions. Binding assays revealed that an I37K substitution in the N-terminal heptad repeat (N-HR) impaired the binding of C34, whereas an N126K substitution in the C-HR enhanced the binding to mutated N-HR, indicating that both mutations were directly involved in resistance. 2005 Journal of virology Abstract HIV I37K;N126K 32;129 36;134 15613309 Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues. Following infection of P4 cells, the BV34 mutant, but not viruses expressing the M184V mutation or M41L+T215Y, exhibited a defect in DNA synthesis. 2005 Journal of virology Abstract HIV M184V;M41L;T215Y 81;99;104 86;103;109 15613309 Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues. Importantly, however, for mutants carrying the M184V mutation or M41L+T215Y mutations, a defect could be detected by using target cells in which dATP pools had been reduced by pretreatment with hydroxyurea. 2005 Journal of virology Abstract HIV M184V;M41L;T215Y 47;65;70 52;69;75 15613309 Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues. Three recombinant viruses derived from three pNL4-3 molecular clones expressing mutations associated with resistance to zidovudine: a clone expressing RT mutation M184V, a clone expressing mutations M41L plus T215Y (M41L+T215Y), and clinical isolate BV34 (carrying seven resistance mutations). 2005 Journal of virology Abstract HIV M184V;M41L;M41L;T215Y;T215Y 163;199;216;209;221 168;203;220;214;226 RT 151 153 15613319 Covalent modification of human immunodeficiency virus type 1 p6 by SUMO-1. As previously reported, though, HIV-1 bearing the p6-K27R mutation replicated just like the wild type. 2005 Journal of virology Abstract HIV K27R 53 57 Gag 50 52 15613319 Covalent modification of human immunodeficiency virus type 1 p6 by SUMO-1. HIV-1 bearing the p6-K27R mutation was insensitive to SUMO-1 overexpression, suggesting that covalent attachment of SUMO-1 to p6 is detrimental to HIV-1 replication. 2005 Journal of virology Abstract HIV K27R 21 25 Gag;Gag 18;126 20;128 15616314 Drug resistance mutations in the nucleotide binding pocket of human immunodeficiency virus type 1 reverse transcriptase differentially affect the phosphorolysis-dependent primer unblocking activity in the presence of stavudine and zidovudine and its inhibition by efavirenz. Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) derivatives with D113E, Y115F, F116Y, Q151E/N, and M184V mutations were studied for their phosphorolysis-mediated resistance to the nucleoside RT inhibitors (NRTIs) zidovudine and stavudine and for their inhibition by the nonnucleoside analogs (NNRTIs) efavirenz and nevirapine. 2005 Antimicrobial agents and chemotherapy Abstract HIV D113E;F116Y;M184V;Q151E;Q151N;Y115F 88;102;122;109;109;95 93;107;127;116;116;100 RT;NNRTI;NRTI;RT;RT 44;316;229;67;214 65;322;234;69;216 15619654 Prevalence of genotypic resistance in untreated HIV-infected patients. I84V was the second most frequently detected mutation (13/24, 54.16%). 2004 Revista espanola de quimioterapia Abstract HIV I84V 0 4 15619654 Prevalence of genotypic resistance in untreated HIV-infected patients. The V82A mutation was found alone (66.6%) and it was found together with the I84V mutation in five samples (20.83%). 2004 Revista espanola de quimioterapia Abstract HIV I84V;V82A 77;4 81;8 15619654 Prevalence of genotypic resistance in untreated HIV-infected patients. Using LiPA P, mutations were detected in 16.21% of cases, with V82A being the most frequently detected mutation (15/24, 62.50%) in nine samples. 2004 Revista espanola de quimioterapia Abstract HIV V82A 63 67 15627034 Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy. Seven primary mutations, V106A (one), Y181C (two), G190A (one), K101E (one), M184V (one), T215S (one) were detected in five (13%) women. 2005 AIDS (London, England) Abstract HIV G190A;K101E;M184V;T215S;V106A;Y181C 51;64;77;90;25;38 56;69;82;95;30;43 15632156 Folding regulates autoprocessing of HIV-1 protease precursor. As both D25N mutant and wild-type PR are known to fold efficiently to the same native dimeric form, we infer that TFR cleavage enables removal of the non-native type of preferences in the PR domain to cause constructive folding of the protein. 2005 The Journal of biological chemistry Abstract HIV D25N 8 12 PR;PR 34;188 36;190 15632156 Folding regulates autoprocessing of HIV-1 protease precursor. However, NMR structural characterization of the precursor containing a mutation, D25N in the PR at pH 5.2 and 32 degrees C under different conditions of partial and complete denaturation by urea, indicate that the precursor has a high tendency to be unfolded. 2005 The Journal of biological chemistry Abstract HIV D25N 81 85 PR 93 95 15634015 Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl)carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives. highly active against wild type and some clinically relevant resistant strains (Y181C, the double mutant K103N-Y181C, and the K103R-V179D-P225H strain, highly resistant to efavirenz). 2005 Journal of medicinal chemistry Abstract HIV K103N;K103R;P225H;V179D;Y181C;Y181C 105;126;138;132;80;111 110;131;143;137;85;116 15646062 Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients. Collectively, these factors might explain the residual antiviral effect and clinical benefit observed with continued use of 3TC in combination therapy regimens following the emergence of M184V. 2004 The new microbiologica Abstract HIV M184V 187 192 15646062 Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients. In addition, M184V may affect viral transmission and immunological response. 2004 The new microbiologica Abstract HIV M184V 13 18 15646062 Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients. Interestingly, the presence of M184V is also associated with alteration of several mechanisms relating to RT function that include decreased RTprocessivity, reduced nucleotide-dependent primer unblocking, increased fidelity, hypersensitization to other NRTIs, impaired viral fitness, and delayed appearance of mutations in RT that are responsible for resistance to thymidine analogues. 2004 The new microbiologica Abstract HIV M184V 31 36 NRTI;RT;RT 253;106;323 258;108;325 15646062 Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients. The M184V substitution in HIV-1 RT develops rapidly following initiation of therapy with 3TC and confers high-level phenotypic resistance to this drug both in vitro and in vivo. 2004 The new microbiologica Abstract HIV M184V 4 9 RT 32 34 15646065 Resistance and replicative capacity of HIV-1 strains selected in vivo by long-term enfuvirtide treatment. In particular, these mutations clustered in two distinct regions: (i) a mutational hot-spot localized, as previously described, in the first residues of the N-HR domain, with position number 38 as the most heavily mutated, but including also a G36V, a N42D/T, a N43D, a L44M and a L45M; (ii) other mutations were localized further downstream, within N-HR/C-HR junction and in the C-HR. 2004 The new microbiologica Abstract HIV G36V;L44M;L45M;N42D;N42T;N43D 244;270;281;252;252;262 248;274;285;258;258;266 15648062 Polymorphism and drug-selected mutations in the reverse transcriptase gene of HIV-2 from patients living in southeastern France. As in HIV-1, substitution M184V was found in 3TC-treated patients. 2005 Journal of medical virology Abstract HIV M184V 26 31 15648062 Polymorphism and drug-selected mutations in the reverse transcriptase gene of HIV-2 from patients living in southeastern France. Four newly or rarely described NRTI-selected mutations were observed: I5V, K35R, F214L, and K223R. 2005 Journal of medical virology Abstract HIV F214L;I5V;K223R;K35R 81;70;92;75 86;73;97;79 NRTI 31 35 15648062 Polymorphism and drug-selected mutations in the reverse transcriptase gene of HIV-2 from patients living in southeastern France. In HIV-2-infected patients receiving NRTI-containing therapies, specific genotypic patterns were observed with a high frequency of mutation Q151M (in 45% of patients) often associated with 70R, 115F, 214L, and/or 223R, which might compose an HIV-2 multi-NRTI resistance complex. 2005 Journal of medical virology Abstract HIV Q151M 140 145 NRTI;NRTI 37;254 41;258 15650204 Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag. Although wild-type levels of membrane binding were restored to the M368A Gag by a second-site L20K mutation within matrix, the resultant Gag mutant L20K-M368A remained defective in virus production. 2005 Journal of virology Abstract HIV L20K;L20K;M368A;M368A 94;148;67;153 98;152;72;158 Matrix;Gag;Gag 115;73;137 121;76;140 15650204 Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag. Based on the myristyl switch model, we propose that the M368A mutation inhibits Gag multimerization and, as a result, restricts the binding of Gag to cellular membranes. 2005 Journal of virology Abstract HIV M368A 56 61 Gag;Gag 80;143 83;146 15650204 Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag. Further analysis revealed that the majority of membrane-bound M368A Gag proteins were small oligomers, indicating a multimerization defect. 2005 Journal of virology Abstract HIV M368A 62 67 Gag 68 71 15650204 Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag. In support of this observation, purified recombinant Gag derivatives containing the M368A mutation formed much lower amounts of high-molecular-weight complexes that were pelletable at 21,000 x g than did wild-type Gag. 2005 Journal of virology Abstract HIV M368A 84 89 Gag;Gag 53;214 56;217 15650204 Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag. In this study, we demonstrate that an M368A mutation within SP1 severely diminished the ability of Gag to associate with cellular membranes. 2005 Journal of virology Abstract HIV M368A 38 43 SP1;Gag 60;99 63;102 15650204 Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag. This latter deficit was partially consequent to the binding of L20K-M368A Gag to nonraft membranes as opposed to raft association seen for wild-type Gag. 2005 Journal of virology Abstract HIV L20K;M368A 63;68 67;73 Gag;Gag 74;149 77;152 15655750 Drug-resistant HIV infection among drug-naive patients in Israel. In addition, 1 subject with A subtypes, 2 with subtype B, and 10 with subtype C had secondary mutations (protease: M46I; reverse transcriptase: A98G, K101Q, and V108I). 2005 Clinical infectious diseases Abstract HIV A98G;K101Q;M46I;V108I 144;150;115;161 148;155;119;166 RT;PR 121;105 142;113 15655750 Drug-resistant HIV infection among drug-naive patients in Israel. RESULTS: Major drug resistance mutations (protease: L90M; reverse transcriptase: M41L, K103N, V106M, M184V, Y181S, G190A, L210W, T215Y/F, and K219R) were detected in 1 subject with A subtype, 3 with subtype B, and 9 with subtype C. 2005 Clinical infectious diseases Abstract HIV G190A;K103N;K219R;L210W;L90M;M184V;M41L;T215F;T215Y;V106M;Y181S 115;87;142;122;52;101;81;129;129;94;108 120;92;147;127;56;106;85;136;136;99;113 RT;PR 58;42 79;50 15668550 Early virological failure in treatment-naive HIV-infected adults receiving didanosine and tenofovir plus efavirenz or nevirapine. At month 6, the mutations detected were K65R, L74V, L100I, K103N/R/T, Y181C and G190E/Q/S. 2005 AIDS (London, England) Abstract HIV G190E;G190Q;G190S;K103N;K103R;K103T;K65R;L100I;L74V;Y181C 80;80;80;59;59;59;40;52;46;70 89;89;89;68;68;68;44;57;50;75 15670903 Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: synthesis and structure-activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives. Compound 11g (YM-215389), a combination of 2-hydroxyphenyl and 4-chloro-5-isopropylthiazole moieties, proved to be the most active against both K103N and Y181C RTs with IC50 values of 0.043 and 0.013 microM, respectively. 2005 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 144;154 149;159 RT 160 163 15670903 Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: synthesis and structure-activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives. Introduction of a 2-cyanophenyl ring into these moieties significantly enhanced anti-HIV-1 activity, whereas a 2-hydroxyphenyl group endowed potent activity against RTs, including K103N and Y181C mutants. 2005 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 180;190 185;195 RT 165 168 15670903 Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: synthesis and structure-activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives. These compounds were found to be highly potent inhibitors of the wild type (WT) and Y181C mutant reverse transcriptases (RTs) and modest inhibitors of K103N RT. 2005 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 151;84 156;89 RT;RT;RT 97;121;157 119;124;159 15680427 Mechanism of action and resistant profile of anti-HIV-1 coumarin derivatives. An E138K mutation in the non-nucleoside RT inhibitors (NNRTIs) binding pocket of HIV-1 RT confers resistance to DCK and its chromone derivative, DCP8. 2005 Virology Abstract HIV E138K 3 8 NNRTI;RT;RT 55;40;87 61;42;89 15680427 Mechanism of action and resistant profile of anti-HIV-1 coumarin derivatives. However, the DCK-escape virus carrying the E138K mutation remains resistant to DCP8. 2005 Virology Abstract HIV E138K 43 48 15680427 Mechanism of action and resistant profile of anti-HIV-1 coumarin derivatives. Our results indicate that a single amino acid mutation, E138K in HIV-1 RT, is sufficient to confer DCK resistance. 2005 Virology Abstract HIV E138K 56 61 RT 71 73 15681450 Genetic analyses of DNA-binding mutants in the catalytic core domain of human immunodeficiency virus type 1 integrase. HIV-1(Q62K), HIV-1(H67E), HIV-1(N120K), and HIV-1(N155K) were also class I mutants, supporting findings that Gln-62 and Asn-120 interact with viral and target DNA, respectively, and suggesting similar integration-specific roles for His-67 and Asn-155. 2005 Journal of virology Abstract HIV H67E;N120K;N155K;Q62K 19;32;50;6 23;37;55;10 15681450 Genetic analyses of DNA-binding mutants in the catalytic core domain of human immunodeficiency virus type 1 integrase. We additionally characterized E138K as an intramolecular suppressor of Gln-62 mutant virus and IN. 2005 Journal of virology Abstract HIV E138K 30 35 IN 95 97 15681450 Genetic analyses of DNA-binding mutants in the catalytic core domain of human immunodeficiency virus type 1 integrase. Whereas HIV-1(P145A) and HIV-1(Q146K) grew like the wild type, HIV-1(N144K) and HIV-1(Q148L) were class I mutants, reinforcing previous results that Gln-148 is important for DNA binding and uncovering for the first time an important role for Asn-144 in integration. 2005 Journal of virology Abstract HIV N144K;P145A;Q146K;Q148L 69;14;31;86 74;19;36;91 15708638 6-[1-(4-Fluorophenyl)methyl-1H-pyrrol-2-yl)]-2,4-dioxo-5-hexenoic acid ethyl ester a novel diketo acid derivative which selectively inhibits the HIV-1 viral replication in cell culture and the ribonuclease H activity in vitro. Similar results were obtained against the Y181C and Y181C/K103N HIV-1 NNRTI resistant mutant strains. 2005 Antiviral research Abstract HIV K103N;Y181C;Y181C 58;42;52 63;47;57 NNRTI 70 75 15708996 Vpr protein of human immunodeficiency virus type 1 binds to 14-3-3 proteins and facilitates complex formation with Cdc25C: implications for cell cycle arrest. Vpr expression shifted localization of the mutant Cdc25C S216A to the cytoplasm, indicating that Vpr promotes the association of 14-3-3 and Cdc25C, independently of the presence of serine 216. 2005 Journal of virology Abstract HIV S216A 57 62 Vpr;Vpr 0;97 3;100 15708996 Vpr protein of human immunodeficiency virus type 1 binds to 14-3-3 proteins and facilitates complex formation with Cdc25C: implications for cell cycle arrest. Vpr mutant R80A, which is inactive in cell cycle arrest, did not interact with 14-3-3. 2005 Journal of virology Abstract HIV R80A 11 15 Vpr 0 3 15713622 Displacement of SATB1-bound histone deacetylase 1 corepressor by the human immunodeficiency virus type 1 transactivator induces expression of interleukin-2 and its receptor in T cells. Transduction with SATB1 interaction-deficient soluble Tat (Tat 40-72) and reporter assays using a transactivation-negative mutant (C22G) of Tat unequivocally demonstrated that the displacement of HDAC1 itself is sufficient for derepression of these promoters in vivo. 2005 Molecular and cellular biology Abstract HIV C22G 131 135 Tat;Tat;Tat 54;59;140 57;62;143 15714296 Quantitative structure-activity relationship by CoMFA for cyclic urea and nonpeptide-cyclic cyanoguanidine derivatives on wild type and mutant HIV-1 protease. The predicted biological activities of the: (i) XNO63 (inhibitory activity on the mutant HIV-1 PR V82A), (ii) SB570 (inhibiting the mutant HIV-1 PR V82I) and also (iii) XV652 (during the interaction with the mutant HIV-1 PR V82F) were in good agreement with the experimental values. 2005 Journal of molecular modeling Abstract HIV V82A;V82F;V82I 98;224;148 102;228;152 PR;PR;PR 95;145;221 97;147;223 15714296 Quantitative structure-activity relationship by CoMFA for cyclic urea and nonpeptide-cyclic cyanoguanidine derivatives on wild type and mutant HIV-1 protease. Using the CoMFA method, we also predicted the biological activity of 14 cyclic urea derivatives that inhibit the HIV-1 protease mutants V82A, V82I and V82F. 2005 Journal of molecular modeling Abstract HIV V82A;V82F;V82I 136;151;142 140;155;146 PR 119 127 15714420 Development of HIV with drug resistance after CD4 cell count-guided structured treatment interruptions in patients treated with highly active antiretroviral therapy after dual-nucleoside analogue treatment. RESULTS: After STI, one major drug-resistance mutation occurred (T215Y), and, in the 4 samples with preexisting major mutations (D67N [n=2], K70R [n=2], T215Y [n=2], and T215I [n=1]), the mutations disappeared. 2005 Clinical infectious diseases Abstract HIV D67N;K70R;T215I;T215Y;T215Y 129;141;170;65;153 134;145;175;70;158 15715487 Synthesis and evaluation of double-prodrugs against HIV. Conjugation of D4T with 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, emivirine)-type reverse transcriptase inhibitors via the SATE prodrug approach. The double-prodrugs 1, 2, and 3 all had good activities against wild-type HIV-1, Y181C mutant, and also against a HIV-2 strain that was resistant to NNRTIs. 2005 Journal of medicinal chemistry Abstract HIV Y181C 81 86 NNRTI 149 155 15722032 Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in the gp41 region of different HIV-1 genetic forms from T20 naive patients. Different substitutions were related to subtypes: N42S in subtypes A, B, G and C, but not in F, Q56R in subtype A from CRF02_AG, and L54M in subtype B from CRF14_BG. 2005 Journal of clinical virology Abstract HIV L54M;N42S;Q56R 133;50;96 137;54;100 15722032 Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in the gp41 region of different HIV-1 genetic forms from T20 naive patients. We analyzed the resistance-associated mutations previously described: Q32H/R, G36D/S, I37V, V38A/M, Q39R/H, Q40H, N42T/D/Q/H, N43D/S/K/Q, L44M, L45M, R46M and V69I. 2005 Journal of clinical virology Abstract HIV G36D;G36S;I37V;L44M;L45M;N42D;N42H;N42Q;N42T;N43D;N43K;N43Q;N43S;Q32H;Q32R;Q39H;Q39R;Q40H;R46M;V38A;V38M;V69I 78;78;86;138;144;114;114;114;114;126;126;126;126;70;70;100;100;108;150;92;92;159 84;84;90;142;148;124;124;124;124;136;136;136;136;76;76;106;106;112;154;98;98;163 15727860 5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors belonging to the DABO family. Against the Y181C mutant strain, 2,6-difluorobenzyl-alpha-methylthymine derivatives 4d, 5h'-n' showed the highest potency and selectivity among tested compounds, both a properly sized C(2)-NH side chain and the presence of two methyl groups (at C(5) and benzylic positions) being crucial for high antiviral action. 2005 Bioorganic & medicinal chemistry Abstract HIV Y181C 12 17 15727860 5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors belonging to the DABO family. Biological evaluation indicated the importance of the further anchor point of compounds 4, 5 into the non-nucleoside binding site (NNBS): newly synthesized compounds were highly active against both wild type and the Y181C HIV-1 strains. 2005 Bioorganic & medicinal chemistry Abstract HIV Y181C 216 221 15728915 In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase. Human immunodeficiency virus type 1 (HIV-1) with a lysine-to-arginine substitution at codon 65 (HIV-1(65R)) of reverse transcriptase (RT) can rapidly emerge in patients being treated with specific combinations of nucleoside analog RT inhibitors (NRTIs). 2005 Antimicrobial agents and chemotherapy Abstract HIV K65R 51 94 RT;NRTI;RT;RT 111;246;134;231 132;251;136;233 15731227 Selection of resistance in protease inhibitor-experienced, human immunodeficiency virus type 1-infected subjects failing lopinavir- and ritonavir-based therapy: mutation patterns and baseline correlates. Less common mutations, such as L33F, I50V, and V32I together with I47V/A, were also selected; however, new mutations at positions 84, 90, and 71 were not observed. 2005 Journal of virology Abstract HIV I47A;I47V;I50V;L33F;V32I 66;66;37;31;47 72;72;41;35;51 15748098 Amprenavir or fosamprenavir plus ritonavir in HIV infection: pharmacology, efficacy and tolerability profile. Although the I50V amino acid substitution is the key mutation conferring resistance to amprenavir, the accumulation of several mutations is needed to increase the IC50 (concentration that produces 50% inhibition) of amprenavir. 2005 Drugs Abstract HIV I50V 13 17 15748098 Amprenavir or fosamprenavir plus ritonavir in HIV infection: pharmacology, efficacy and tolerability profile. When used with ritonavir, the accumulation of six or more mutations among L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S and I84V leads to clear decrease in viral response to treatment. 2005 Drugs Abstract HIV E35D;I54V;I84V;K20M;K20R;L10F;L10I;L10V;L63P;R41K;V82A;V82F;V82S;V82T 92;104;131;84;84;74;74;74;110;98;116;116;116;116 96;108;135;90;90;82;82;82;114;102;126;126;126;126 15750116 Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. A marked impairment in replicative fitness was observed in association with the selection of viruses carrying the K65R mutation in all patients. 2005 Journal of clinical microbiology Abstract HIV K65R 114 118 15750116 Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. Here, we have used for the first time primary HIV-1 isolates from individuals who developed the K65R mutation while enrolled in a clinical trial of tenofovir to analyze the impact of this mutation on HIV-1 replicative fitness. 2005 Journal of clinical microbiology Abstract HIV K65R 96 100 15750116 Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) resistance mutation K65R confers intermediate levels of resistance to several RT inhibitors, including a three- to fourfold reduction of tenofovir susceptibility. 2005 Journal of clinical microbiology Abstract HIV K65R 95 99 RT;RT;RT 48;71;153 69;73;155 15750116 Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. These results support a reduction in in vivo replication for K65R mutant viruses. 2005 Journal of clinical microbiology Abstract HIV K65R 61 65 15751775 Early virological failure with a combination of tenofovir, didanosine and efavirenz. Additionally, L74V/I and K65R were detected in four and two patients, respectively. 2005 Antiviral therapy Abstract HIV K65R;L74I;L74V 25;14;14 29;20;20 15751775 Early virological failure with a combination of tenofovir, didanosine and efavirenz. At failure, G190S/E alone or associated with K103N and K101R mutations was detected in five patients, and K103N/L1001/V108l in the sixth patient. 2005 Antiviral therapy Abstract HIV K103N;K103V;G190E;G190S;K101R;K103N 106;106;12;12;55;45 111;111;19;19;60;50 15757587 [Study of resistance using the TRUGENE HIV-1 genotyping system and analysis of agreement between rule-based algorithms and virtual phenotyping]. For the IP: key mutations L90M (26.1%), M46I (18.1%) and V82AFTS (12.9%); and accessory mutations L63P (50.5%), A71V (27.2%), L10I (25.2%) and M36I (19.2%). 2005 Enfermedades infecciosas y microbiologia clinica Abstract HIV A71V;L10I;L63P;L90M;M36I;M46I;V82A;V82F;V82S;V82T 112;126;98;26;143;40;57;57;57;57 116;130;102;30;147;44;64;64;64;64 15757587 [Study of resistance using the TRUGENE HIV-1 genotyping system and analysis of agreement between rule-based algorithms and virtual phenotyping]. For the ITINN K103N (25.8%), Y181C (11.2%) and G190A (10.9%). 2005 Enfermedades infecciosas y microbiologia clinica Abstract HIV G190A;K103N;Y181C 47;14;29 52;19;34 15757587 [Study of resistance using the TRUGENE HIV-1 genotyping system and analysis of agreement between rule-based algorithms and virtual phenotyping]. The 69 insertion and Q151M complex had low representativity. 2005 Enfermedades infecciosas y microbiologia clinica Abstract HIV Q151M 21 26 15757587 [Study of resistance using the TRUGENE HIV-1 genotyping system and analysis of agreement between rule-based algorithms and virtual phenotyping]. The more frequent mutations to the ITIAN were T215Y/F (37.2%) and M184V (32.9%) following by other NAMS. 2005 Enfermedades infecciosas y microbiologia clinica Abstract HIV M184V;T215F;T215Y 66;46;46 71;53;53 15761606 Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil. Many mutations associated with reduced susceptibility to nucleoside or non-nucleoside reverse transcriptase inhibitors were detected: M41L (11%), E44D (4%), D67N (11%), T69D (2%), K70R (11%), L74V (2%), L100I (4%), K103N (18%), V118I (9%), Y181C (11%), M184V (18%), G190A (4%), T215Y (4%), and K219E (4%). 2004 Memorias do Instituto Oswaldo Cruz Abstract HIV D67N;E44D;G190A;K103N;K219E;K70R;L100I;L74V;M184V;M41L;T215Y;T69D;V118I;Y181C 157;146;266;215;294;180;203;192;253;134;278;169;228;240 161;150;271;220;299;184;208;196;258;138;283;173;233;245 NNRTI 71 107 15761606 Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil. Minor mutations were also found at the protease gene: L10I/V (7%), K20M (2%), M36I (11%), L63P (20%), A71T (2%), and V77I (7%). 2004 Memorias do Instituto Oswaldo Cruz Abstract HIV A71T;K20M;L10I;L10V;L63P;M36I;V77I 102;67;54;54;90;78;117 106;71;60;60;94;82;121 PR 39 47 15761606 Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil. One major protease inhibitor resistance-associated mutation, I50V, was detected in 38% of the samples. 2004 Memorias do Instituto Oswaldo Cruz Abstract HIV I50V 61 65 PR 10 18 15764656 Comparison of multiple molecular dynamics trajectories calculated for the drug-resistant HIV-1 integrase T66I/M154I catalytic domain. Four different conformations of IN were chosen from a prior molecular dynamics (MD) simulation on the modeled IN T66I/M154I catalytic core domain as starting points for additional MD studies. 2005 Biophysical journal Abstract HIV M154I;T66I 118;113 123;117 IN;IN 32;110 34;112 15764961 Comparison of the precision and sensitivity of the Antivirogram and PhenoSense HIV drug susceptibility assays. The PhenoSense assay was also significantly more likely than the Antivirogram assay to detect resistance to abacavir, didanosine, and stavudine in isolates with the common drug resistance mutations M41L, M184V, and T215Y (+/-L210W). 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L210W;M184V;M41L;T215Y 225;204;198;215 230;209;202;220 15767436 Variants of human immunodeficiency virus type 1 that efficiently use CCR5 lacking the tyrosine-sulfated amino terminus have adaptive mutations in gp120, including loss of a functional N-glycan. The adapted variants had additional mutations in their V3 loops, as well as one in the V2 stem (S193N) and four alternative mutations in the V4 loop that eliminated the same N-linked oligosaccharide from position N403. 2005 Journal of virology Abstract HIV S193N 96 101 15771439 4-Benzyl and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones: in vitro evaluation of new C-3-amino-substituted and C-5,6-alkyl-substituted analogues against clinically important HIV mutant strains. Of the 17 new 5/6-modified analogues prepared, compounds 31b and 32b substituted at C-5 by an extended nonpolar chain containing an ether function and a C-6 methyl group and compound 35 bearing a C-5 ethyl/C-6 hydroxymethyl substituent pattern were selected on the basis of their in vitro activity against wild-type HIV and the three principle mutant strains, K103N, Y181C, and Y188L. 2005 Journal of medicinal chemistry Abstract HIV K103N;Y181C;Y188L 360;367;378 365;372;383 15771439 4-Benzyl and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones: in vitro evaluation of new C-3-amino-substituted and C-5,6-alkyl-substituted analogues against clinically important HIV mutant strains. Of these, the N-methyl-N-(2-methoxyethyl)-substituted compounds 40, 42, and 62, as well as the doubly modified compounds 77a and 77b, were selected from the initial screen and were subsequently shown to be active at sub-micromolar concentrations (IC(50)'s) against all the other mutant strains except K103N + Y181C and F227L + V106A. 2005 Journal of medicinal chemistry Abstract HIV F227L;K103N;V106A;Y181C 319;301;327;309 324;306;332;314 15771439 4-Benzyl and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones: in vitro evaluation of new C-3-amino-substituted and C-5,6-alkyl-substituted analogues against clinically important HIV mutant strains. When tested further, it was shown that these molecules, and in particular compound 35, are globally more active than 9, 10, and efavirenz against an additional eight single [L100I, K101E, V106A, E138K, V179E, G190A/S, and F227C] and four double HIV mutant strains [L100I + K103N, K101E + K103N, K103N + Y181C, and F227L + V106A], which are clinically relevant. 2005 Journal of medicinal chemistry Abstract HIV E138K;F227C;F227L;G190A;G190S;K101E;K101E;K103N;K103N;K103N;L100I;L100I;V106A;V106A;V179E;Y181C 195;222;314;209;209;181;280;273;288;295;174;265;188;322;202;303 200;227;319;216;216;186;285;278;293;300;179;270;193;327;207;308 15776380 HIV-1 drug resistance: degree of underestimation by a cross-sectional versus a longitudinal testing approach. For example, the prevalence of resistance-associated mutation M184V/I was 25.5% in the most recent genotypes and 58.8% in available historical genotypes. 2005 The Journal of infectious diseases Abstract HIV M184I;M184V 62;62 69;69 15778973 Relationship between drug resistance mutations, plasma viremia, and CD4+ T-cell counts in patients with chronic HIV infection. However, in the multivariate analyses, only a lower viral load and the presence of K70R were significantly associated with higher CD4+ cell counts. 2005 Journal of medical virology Abstract HIV K70R 83 87 15778973 Relationship between drug resistance mutations, plasma viremia, and CD4+ T-cell counts in patients with chronic HIV infection. In the univariate analysis, a lower viral load (P < 0.0001), the presence of drug-resistant viruses (P = 0.038), and specific mutations in the reverse transcriptase (RT) gene [presence of M184V (P = 0.016) or K70R (P < 0.0001), and lack of L74V (P < 0.003)] were all associated with higher CD4+ counts. 2005 Journal of medical virology Abstract HIV K70R;L74V;M184V 209;240;188 213;244;193 RT;RT 143;166 164;168 15782177 LigAmp for sensitive detection of single-nucleotide differences. LigAmp detected the K103N HIV-1 drug resistance mutation at 0.01% in plasmid mixtures and at approximately 0.1% in DNA amplified from plasma HIV-1. 2004 Nature methods Abstract HIV K103N 20 25 15789428 Quantum study of mutational effect in binding of efavirenz to HIV-1 RT. Full quantum mechanical computational study has been carried out to study binding of efavirenz (EFZ), a second generation FDA approved nonnucleoside inhibitor, to HIV-1 reverse transcriptase (RT) and its K103N and Y181C mutants using the MFCC (molecular fractionation with conjugate caps) method. 2005 Proteins Abstract HIV K103N;Y181C 204;214 209;219 RT;RT 169;192 190;194 15789428 Quantum study of mutational effect in binding of efavirenz to HIV-1 RT. The small loss of binding to K103N mutant by Efavirenz can be attributed to a slightly weakened attractive interaction between the drug and Lys101 due to a conformational change of mutation. 2005 Proteins Abstract HIV K103N 29 34 15789428 Quantum study of mutational effect in binding of efavirenz to HIV-1 RT. The small loss of binding to Y181C mutant by efavirenz can be attributed to the Glu698 residue moving closer to EFZ due to conformational change, which results in an increase of repulsive energy relative to the wild type (WT). 2005 Proteins Abstract HIV Y181C 29 34 15794743 Observation of a tetrahedral reaction intermediate in the HIV-1 protease-substrate complex. The crystal structure of the C95M/C1095A HIV-1 protease tethered dimer shows a distinctive feature in which the two flaps of the enzyme are in a 'closed conformation' even in the unliganded state. 2005 The Biochemical journal Abstract HIV C1095A;C95M 34;29 40;33 PR 47 55 15794978 Evaluation of an oligonucleotide ligation assay for detection of mutations in HIV-1 subtype C individuals who have high level resistance to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors. For codons, K103N, Y181C, K65R, Q151M, M184V and T215Y/F, four or more mismatches compared to the probe or mismatches less than four bases from the ligation site were not tolerated. 2005 Journal of virological methods Abstract HIV K103N;K65R;M184V;Q151M;T215F;T215Y;Y181C 12;26;39;32;49;49;19 17;30;44;37;56;56;24 15794978 Evaluation of an oligonucleotide ligation assay for detection of mutations in HIV-1 subtype C individuals who have high level resistance to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors. The aim was to evaluate OLA for detecting mutations K103N, Y181C, K65R, Q151M, M184V and T215Y/F in subtype C. 2005 Journal of virological methods Abstract HIV K103N;K65R;M184V;Q151M;T215F;T215Y;Y181C 52;66;79;72;89;89;59 57;70;84;77;96;96;64 15795255 A substitution in rous sarcoma virus integrase that separates its two biologically relevant enzymatic activities. Even with Mg2+, the substituted proteins exhibited greater specificity than the wild type, especially the S124D protein. 2005 Journal of virology Abstract HIV S124D 106 111 15795255 A substitution in rous sarcoma virus integrase that separates its two biologically relevant enzymatic activities. Moreover, RSV virions containing integrase with the S124D mutation were unable to replicate in cell cultures. 2005 Journal of virology Abstract HIV S124D 52 57 IN 33 42 15795255 A substitution in rous sarcoma virus integrase that separates its two biologically relevant enzymatic activities. Thus, the S124D protein has separated the processing and joining activities of integrase. 2005 Journal of virology Abstract HIV S124D 10 15 IN 79 88 15795255 A substitution in rous sarcoma virus integrase that separates its two biologically relevant enzymatic activities. Unexpectedly, however, the S124D protein was significantly impaired at catalyzing the insertion of viral DNA ends in reactions with Mn2+ and joining was undetectable in reactions with Mg2. 2005 Journal of virology Abstract HIV S124D 27 32 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. Among patients with a known treatment history, K103S/T/H were observed primarily in individuals failing NNRTI-containing regimens. 2005 AIDS (London, England) Abstract HIV K103H;K103S;K103T 47;47;47 56;56;56 NNRTI 104 109 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. BACKGROUND: The K103N mutation in HIV-1 reverse transcriptase (RT) confers high-level resistance to current non-nucleoside reverse transcriptase inhibitors (NNRTI). 2005 AIDS (London, England) Abstract HIV K103N 16 21 NNRTI;RT;NNRTI;RT 108;40;157;63 144;61;162;65 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. CONCLUSION: Variants at HIV RT codon 103 other than K103N are observed relatively rarely in clinical isolates, but K103 S, T and H confer decreased susceptibility to NNRTI. 2005 AIDS (London, England) Abstract HIV K103N;K103S 52;115 57;121 NNRTI;RT 166;28 171;30 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. K103R/Q-containing clinical isolates remained phenotypically susceptible to NNRTI, whereas K103S/T/H-containing isolates showed over 10-fold decreased NNRTI susceptibility. 2005 AIDS (London, England) Abstract HIV K103H;K103Q;K103R;K103S;K103T 91;0;0;91;91 100;7;7;100;100 NNRTI;NNRTI 76;151 81;156 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. K103T/Q/H substitutions were observed only rarely (<0.2%). 2005 AIDS (London, England) Abstract HIV K103H;K103Q;K103T 0;0;0 9;9;9 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. RESULTS: K103N, R and S were observed in 29, 1.8, and 0.9% of Virco isolates and in 16, 1.5 and 0.4% of British Columbia isolates. 2005 AIDS (London, England) Abstract HIV K103N 9 14 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. Site-directed mutants confirmed decreased susceptibility to NNRTI in K103S/T/H-containing recombinants. 2005 AIDS (London, England) Abstract HIV K103H;K103S;K103T 69;69;69 78;78;78 NNRTI 60 65 15802972 Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. The prevalence of unusual codon 103 substitutions remained stable over 5 years, except K103S, which increased over fourfold in both datasets. 2005 AIDS (London, England) Abstract HIV K103S 87 92 15802984 Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. Moreover, the S68G and V75I mutations are not necessarily linked with K65R, and could thus have their own resistance effect. 2005 AIDS (London, England) Abstract HIV K65R;S68G;V75I 70;14;23 74;18;27 15802984 Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. We analysed the quasispecies at a clonal level in patients whose plasma genotypic test harboured K65R with L74V or thymidine analogue mutations (TAM). 2005 AIDS (London, England) Abstract HIV K65R;L74V 97;107 101;111 15802984 Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. We found no clone bearing both K65R and L74V substitutions. 2005 AIDS (London, England) Abstract HIV K65R;L74V 31;40 35;44 15802984 Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. We showed that the K65R and TAM such as M41L, D67N, T215Y/D, L210W and K219E can be borne by the same virus. 2005 AIDS (London, England) Abstract HIV D67N;K219E;K65R;L210W;M41L;T215D;T215Y 46;71;19;61;40;52;52 50;76;23;66;44;59;59 15811849 An amino-terminal motif functions as a second nuclear export sequence in BRCA1. Mutation of leucine 28 to an alanine reduced nuclear export by approximately 75%. 2005 The Journal of biological chemistry Abstract HIV L28A 12 36 15815973 Comparative molecular dynamics simulations of HIV-1 integrase and the T66I/M154I mutant: binding modes and drug resistance to a diketo acid inhibitor. In an effort to understand the molecular mechanism of the resistance of T66I/M154I IN to the inhibitor L-731,988 and its specific binding modes, we have carried out docking studies, explicit solvent MD simulations, and binding free energy calculations. 2005 Proteins Abstract HIV M154I;T66I 77;72 82;76 IN 83 85 15815973 Comparative molecular dynamics simulations of HIV-1 integrase and the T66I/M154I mutant: binding modes and drug resistance to a diketo acid inhibitor. MD simulations have been carried out for the T66I/M154I DM IN, DM IN in complex with L-731,988 in 2 different orientations, and 1QS4 IN in complex with L-731,988. 2005 Proteins Abstract HIV M154I;T66I 50;45 55;49 IN;IN;IN 59;66;133 61;68;135 15815973 Comparative molecular dynamics simulations of HIV-1 integrase and the T66I/M154I mutant: binding modes and drug resistance to a diketo acid inhibitor. The results of these simulations show a similar dynamical behavior between T66I/M154I IN alone and in complex with L-731,988, while significant differences are observed in the mobility of the IN catalytic loop (residues 138-149). 2005 Proteins Abstract HIV M154I;T66I 80;75 85;79 IN;IN 86;192 88;194 15821395 High virological failure rate in HIV patients after switching to a regimen with two nucleoside reverse transcriptase inhibitors plus tenofovir. At failure a new pattern, including the K65R mutation with M184V or thymidine analogue mutations, was observed. 2005 AIDS (London, England) Abstract HIV K65R;M184V 40;59 44;64 15840522 Opposing effects of the M368A point mutation and deletion of the SP1 region on membrane binding of human immunodeficiency virus type 1 Gag. In this study, we further showed that the M368A point mutation, but not the DeltaSP1 deletion, severely diminished the levels of membrane-associated Gag proteins. 2005 Virology Abstract HIV M368A 42 47 Gag 149 152 15840522 Opposing effects of the M368A point mutation and deletion of the SP1 region on membrane binding of human immunodeficiency virus type 1 Gag. It has been previously observed that either a M368A substitution within SP1 or the DeltaSP1 deletion impaired virus production. 2005 Virology Abstract HIV M368A 46 51 SP1 72 75 15840522 Opposing effects of the M368A point mutation and deletion of the SP1 region on membrane binding of human immunodeficiency virus type 1 Gag. This membrane binding defect associated with M368A was corrected either by changing NC to the leucine zipper (LZ) motif derived from the yeast transcription factor GCN4 or by a L364A second-site mutation in the context of the first four residues of SP1. 2005 Virology Abstract HIV L364A;M368A 177;45 182;50 SP1;NC 249;84 252;86 15840522 Opposing effects of the M368A point mutation and deletion of the SP1 region on membrane binding of human immunodeficiency virus type 1 Gag. Yet, neither the L364A mutation nor the LZ substitution restored wild type levels of particle production to the M368A Gag. 2005 Virology Abstract HIV L364A;M368A 17;112 22;117 Gag 118 121 15845785 Limited development and progression of resistance of HIV-1 to the nucleoside analogue reverse transcriptase inhibitor lamivudine in human primary macrophages. A fitness assay using wild-type virus and a lamivudine-resistant HIV-1 virus (harbouring the M184V RT mutation) was performed in peripheral blood mononuclear cells. 2005 The Journal of antimicrobial chemotherapy Abstract HIV M184V 93 98 RT 99 101 15845785 Limited development and progression of resistance of HIV-1 to the nucleoside analogue reverse transcriptase inhibitor lamivudine in human primary macrophages. Despite this, the M184V RT mutant virus replicates in M/M, although with a 30% decreased efficiency compared with the wild-type. 2005 The Journal of antimicrobial chemotherapy Abstract HIV M184V 18 23 RT 24 26 15845785 Limited development and progression of resistance of HIV-1 to the nucleoside analogue reverse transcriptase inhibitor lamivudine in human primary macrophages. RESULTS: The mutagenized M184V RT virus showed full resistance to lamivudine in M/M. 2005 The Journal of antimicrobial chemotherapy Abstract HIV M184V 25 30 RT 31 33 15845785 Limited development and progression of resistance of HIV-1 to the nucleoside analogue reverse transcriptase inhibitor lamivudine in human primary macrophages. The M184V RT mutant virus was obtained by site-directed mutagenesis on a CCR5-using HIV-1 backbone. 2005 The Journal of antimicrobial chemotherapy Abstract HIV M184V 4 9 RT 10 12 15845785 Limited development and progression of resistance of HIV-1 to the nucleoside analogue reverse transcriptase inhibitor lamivudine in human primary macrophages. This inefficiency of M/M to develop M184V RT mutated virus is tightly related to the low 2'-deoxynucleotide (dNTP) pool in such cells, which in turn decreases the kinetics of HIV-1-RT. 2005 The Journal of antimicrobial chemotherapy Abstract HIV M184V 36 41 RT;RT 42;181 44;183 15855490 Clinically relevant genotype interpretation of resistance to didanosine. Eight mutations were associated with a reduced response to ddI, M41L, D67N, T69D, L74V, V118I, L210W, T215Y/F, and K219Q/E, and two mutations were associated with a better response, K70R and M184V/I. 2005 Antimicrobial agents and chemotherapy Abstract HIV D67N;K219E;K219Q;K70R;L210W;L74V;M184I;M184V;M41L;T215F;T215Y;T69D;V118I 70;115;115;182;95;82;191;191;64;102;102;76;88 74;122;122;186;100;86;198;198;68;109;109;80;93 15855490 Clinically relevant genotype interpretation of resistance to didanosine. The best prediction of the virologic response to ddI was obtained with a composite score comprising mutations added and subtracted (set II, M41L + T69D + L74V+ T215Y/F + K219Q/E - K70R - M184V/I; P = 4.5 x 10(-9)) and by comparing that to only mutations added (set I, M41L + T69D + L74V + L210W + T215Y/F + K219Q/E; P = 1.2 x 10(-7)). 2005 Antimicrobial agents and chemotherapy Abstract HIV K219E;K219E;K219Q;K219Q;K70R;L210W;L74V;L74V;M184I;M184V;M41L;M41L;T215F;T215F;T215Y;T215Y;T69D;T69D 170;307;170;307;180;289;154;282;187;187;140;268;160;297;160;297;147;275 177;314;177;314;184;294;158;286;194;194;144;272;167;304;167;304;151;279 15855524 Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine. Mutations of leucine 74 to valine and of lysine 65 to arginine had mild to moderate resistance (as high as fivefold). 2005 Antimicrobial agents and chemotherapy Abstract HIV K65R;L74V 41;13 62;33 15855524 Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine. The antiviral activity in PBMCs was not markedly affected by mutations of methionine to valine at position 184 or by thymidine-associated mutations in the viral reverse transcriptase. 2005 Antimicrobial agents and chemotherapy Abstract HIV M184V 74 110 RT 161 182 15855527 Novel human immunodeficiency virus type 1 protease mutations potentially involved in resistance to protease inhibitors. In particular, E34Q, K43T, and K55R, which were associated with lopinavir treatment, correlated with mutations associated with lopinavir resistance (E34Q with either L33F or F53L, or K43T with I54A) or clustered with multi-PI resistance mutations (K43T with V82A and I54V or V82A, V32I, and I47V, or K55R with V82A, I54V, and M46I). 2005 Antimicrobial agents and chemotherapy Abstract HIV E34Q;E34Q;F53L;I47V;I54A;I54V;I54V;K43T;K43T;K43T;K55R;K55R;L33F;M46I;V32I;V82A;V82A;V82A 15;149;174;291;193;267;316;21;183;248;31;300;166;326;281;258;275;310 19;154;178;295;197;271;320;25;187;253;35;304;170;330;285;262;279;314 PI 223 225 15855527 Novel human immunodeficiency virus type 1 protease mutations potentially involved in resistance to protease inhibitors. K45R and K20T, which were associated with nelfinavir treatment, were specifically associated with D30N and N88D and with L90M, respectively. 2005 Antimicrobial agents and chemotherapy Abstract HIV D30N;K20T;L90M;N88D;K45R 98;9;121;107;0 102;13;125;111;4 15855527 Novel human immunodeficiency virus type 1 protease mutations potentially involved in resistance to protease inhibitors. On the other hand, C95F, which was associated with treatment with saquinavir and indinavir, was highly expressed in clusters with either L90M and I93L or V82A and G48V. 2005 Antimicrobial agents and chemotherapy Abstract HIV C95F;G48V;I93L;L90M;V82A 19;163;146;137;154 23;167;150;141;158 15855527 Novel human immunodeficiency virus type 1 protease mutations potentially involved in resistance to protease inhibitors. They never showed positive correlations with PI resistance mutations; if anything, H69N showed a negative correlation with the compensatory mutations M36I and L10I. 2005 Antimicrobial agents and chemotherapy Abstract HIV H69N;L10I;M36I 83;159;150 87;163;154 PI 45 47 15855527 Novel human immunodeficiency virus type 1 protease mutations potentially involved in resistance to protease inhibitors. We also identified three protease mutations (T12A, L63Q, and H69N) whose frequencies significantly decreased in PI-treated patients compared with that in drug-naive patients. 2005 Antimicrobial agents and chemotherapy Abstract HIV H69N;L63Q;T12A 61;51;45 65;55;49 PR;PI 25;112 33;114 1585629 Identification of amino acid residues critical for endonuclease and integration activities of HIV-1 IN protein in vitro. Mutation of a conserved Thr115 to Ala caused a near complete loss of Mg(2+)-dependent integration activity, but only partially effected endonucleolytic cleavage activity of IN. 1992 Virology Abstract HIV T115A 24 37 IN 173 175 15857976 Phenotypic hypersusceptibility to multiple protease inhibitors and low replicative capacity in patients who are chronically infected with human immunodeficiency virus type 1. Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). 2005 Journal of virology Abstract HIV N88S;V82T 189;180 193;185 PR;PR 32;170 40;178 15857986 Amino acid 36 in the human immunodeficiency virus type 1 gp41 ectodomain controls fusogenic activity: implications for the molecular mechanism of viral escape from a fusion inhibitor. The mutation 36G-->D in a primary-isolate-derived Env decreased syncytium-forming activity and infectivity. 2005 Journal of virology Abstract HIV G36D 13 20 Env 50 53 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. A total of 586 patients entered the study and were followed-up over 48 weeks; 281 (48%) were switched to ddl-containing HAART, of whom 105 had the M184V mutation at baseline. 2005 Antiviral therapy Abstract HIV M184V 147 152 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. BACKGROUND: In vitro phenotypic resistance studies suggest that the presence of the M184V mutation leads to a reduction in HIV-1 susceptibility to didanosine (ddl). 2005 Antiviral therapy Abstract HIV M184V 84 89 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. CONCLUSIONS: While the M184V did increase the fold resistance of HIV to ddl, these changes appeared to be lower than the clinically relevant threshold for phenotypic resistance for this drug. 2005 Antiviral therapy Abstract HIV M184V 23 28 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. In the group of patients with the M184V mutation at baseline, the virological outcome was significantly better in those treated with ddl-containing HAART than in those on HAART without ddl (P<0.05). 2005 Antiviral therapy Abstract HIV M184V 34 39 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. In this study, we compared the virological response of ddl- and non-ddl-containing regimens in the presence or absence of the M184V mutation. 2005 Antiviral therapy Abstract HIV M184V 126 131 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. Nonetheless, the median change in VL and percentage of patients attaining an undetectable VL were similar in those taking ddl, irrespective of whether the M184V mutation was present at baseline. 2005 Antiviral therapy Abstract HIV M184V 155 160 15865231 The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. RESULTS: Amongst patients on ddl-containing HAART, median fold changes in phenotypic susceptibility to ddl were greater in patients with the M184V mutation (fold changes of 2.2 vs 1.2, P<0.001). 2005 Antiviral therapy Abstract HIV M184V 141 146 15867968 Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy. The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. 2005 Memorias do Instituto Oswaldo Cruz Abstract HIV M184V 114 119 RT 47 68 15867968 Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. 2005 Memorias do Instituto Oswaldo Cruz Abstract HIV A71V;K103N;L10F;L10R;L63P 174;4;162;162;156 178;9;168;168;160 PR;RT 110;64 118;66 15871131 Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. BACKGROUND: This work evaluates the role of subtype F human immunodeficiency virus type 1 (HIV-1) protease (PR) substitutions L89M and L90M in viral replication and resistance to PR inhibitors (PIs). 2005 The Journal of infectious diseases Abstract HIV L89M;L90M 126;135 130;139 PR;PI;PR;PR 98;194;108;179 106;197;110;181 15871131 Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. CONCLUSION: The L89M mutation in subtype F viruses is a high genetic barrier to the accumulation of the L90M resistance mutation and can function as a resistance mutation, depending on the presence of other polymorphisms in the subtype F PR backbone. 2005 The Journal of infectious diseases Abstract HIV L89M;L90M 16;104 20;108 PR 238 240 15871131 Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. RESULTS: The subtype F clone (89M90L) showed a replicative capacity comparable to that of the PI-susceptible subtype B clone (89L90L) and was more fit than the L89M mutated subtype B clone (89M90L). 2005 The Journal of infectious diseases Abstract HIV L90L;M90L;M90L;L89M 128;192;32;160 132;196;36;164 PI 94 96 15871131 Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. Subtype F isolates presented a phenotypic profile similar to that of subtype B isolates when the M89L mutation was introduced. 2005 The Journal of infectious diseases Abstract HIV M89L 97 101 15871131 Low accumulation of L90M in protease from subtype F HIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism. The L89M mutation impacted phenotypic resistance to all PIs in half of the subtype F isolates but not in the subtype B isolates. 2005 The Journal of infectious diseases Abstract HIV L89M 4 8 PI 56 59 15871775 [Genotypic resistence in patients infected with HIV and its correlation with therapy]. By LiPA, RT mutations were detected in 71.43% of patients, being M184V, T215Y and L41M the most frequent ones. 2005 Medicina clinica Abstract HIV L41M;M184V;T215Y 82;65;72 86;70;77 RT 9 11 15871775 [Genotypic resistence in patients infected with HIV and its correlation with therapy]. Moreover, P mutations were detected in 59.38% of cases, being V82A, L90M and I84V the most frequent ones. 2005 Medicina clinica Abstract HIV I84V;L90M;V82A 77;68;62 81;72;66 15878178 Suppression of multidrug-resistant HIV-1 reverse transcriptase primer unblocking activity by alpha-phosphate-modified thymidine analogues. A dipeptide insertion between codons 69 and 70 together with the amino acid substitution T215Y in the reverse transcriptase (RT)-coding region of human immunodeficiency virus type 1 (HIV-1) strains are known to confer phenotypic resistance to zidovudine (AZT) and stavudine (d4T). 2005 Journal of molecular biology Abstract HIV T215Y 89 94 RT;RT 102;125 123;127 15879710 Characterization of the functional domains of human foamy virus integrase using chimeric integrases. However, these inactive chimeras were efficiently complemented by the point mutants (D164A and E200A) of HFV integrase, indicating that the central domain of HFV integrase possesses potential enzymatic activity but is not able to recognize viral or target DNA without the help of its homologous N-terminal and C-terminal domains. 2005 Molecules and cells Abstract HIV D164A;E200A 85;95 91;100 IN;IN 109;162 118;171 15880183 [Primary resistance to antiretroviral therapy in patients with HIV/AIDS in Chile]. Ten mutations were identified: V179D, L10I/V, M361, L63P, A71T/V, Y115F, V118I and K20R. 2005 Revista medica de Chile Abstract HIV A71T;A71V;K20R;L10I;L10V;L63P;V118I;V179D;Y115F 58;58;83;38;38;52;73;31;66 64;64;87;44;44;56;78;36;71 15885814 Effects of HIV Q151M-associated multi-drug resistance mutations on the activities of (-)-beta-D-1',3'-dioxolan guanine. At the enzyme level, the addition of the A62V mutation to V75I/F77L/F116Y/Q151M moderately (3.4-fold) reversed the resistance to DXG-TP. 2005 Antiviral research Abstract HIV F116Y;F77L;Q151M;V75I;A62V 68;63;74;58;41 73;67;79;62;45 15885814 Effects of HIV Q151M-associated multi-drug resistance mutations on the activities of (-)-beta-D-1',3'-dioxolan guanine. In this study, we evaluated the antiviral activity of (-)-beta-D-1',3'-dioxolan guanine (DXG) towards mutant HIV-1 containing V75I/F77L/F116Y/Q151M (V75Icomplex) and A62V/V75I/F77L/F116Y/Q151M (A62Vcomplex) in MT-2 cells. 2005 Antiviral research Abstract HIV A62V;F116Y;F116Y;F77L;F77L;Q151M;Q151M;V75I;V75I 166;136;181;131;176;142;187;171;126 170;141;186;135;180;147;192;175;130 15885814 Effects of HIV Q151M-associated multi-drug resistance mutations on the activities of (-)-beta-D-1',3'-dioxolan guanine. The A62V mutation significantly increased the rate of incorporation (k(pol)) for both dGTP (3-fold) and DXG-TP (7.9-fold), while the binding affinity of A62V HIV-1 RT for DXG-TP was decreased 14-fold. 2005 Antiviral research Abstract HIV A62V;A62V 4;153 8;157 Pol;RT 71;164 74;166 15885814 Effects of HIV Q151M-associated multi-drug resistance mutations on the activities of (-)-beta-D-1',3'-dioxolan guanine. The multi-drug resistance HIV-1 genotype A62V/V75I/F77L/F116Y/Q151M is associated with resistance to many nucleoside reverse transcriptase inhibitors including AZT, ddI, ddC, d4T, abacavir, and 3TC. 2005 Antiviral research Abstract HIV A62V;F116Y;F77L;Q151M;V75I 41;56;51;62;46 45;61;55;67;50 NRTI 106 138 15885814 Effects of HIV Q151M-associated multi-drug resistance mutations on the activities of (-)-beta-D-1',3'-dioxolan guanine. We further investigated the mechanism of resistance by studying the incorporation of DXG 5'-triphosphate (DXG-TP) during DNA synthesis by mutant enzymes containing single mutations at Q151M or A62V, and the V75Icomplex and A62Vcomplex using pre-steady state kinetic analysis. 2005 Antiviral research Abstract HIV A62V;Q151M 193;184 197;189 15892966 Natural resistance of human immunodeficiency virus type 2 to zidovudine. Among these viruses, the fastest selection of resistance was seen in HIV-1(S215), which acquired S215Y (1-nucleotide change only) at passage 3 after only 17 days in culture. 2005 Virology Abstract HIV S215Y 97 102 15892966 Natural resistance of human immunodeficiency virus type 2 to zidovudine. In contrast, none of the 5 HIV-2 viruses that naturally have S215 acquired S215Y/F or any other RT mutation during 10 passages with AZT (1025-fold increase in AZT concentration). 2005 Virology Abstract HIV S215F;S215Y 75;75 82;82 RT 96 98 15893572 Discrimination of lamivudine resistant minor HIV-1 variants by selective real-time PCR. This sensitive and reliable point-mutation assay, analyzing M184I/V and other important mutations, will be fruitful in gaining new scientific knowledge about the kinetics of resistance mutations in minor viral populations of HIV-1 infected patients at failure of antiretroviral therapy. 2005 Journal of virological methods Abstract HIV M184I;M184V 60;60 67;67 HIV infections 225 239 15898808 The molecular basis of resilience to the effect of the Lys103Asn mutation in non-nucleoside HIV-1 reverse transcriptase inhibitors studied by targeted molecular dynamics simulations. A series of targeted molecular dynamics simulations have been carried out in an attempt to assess the effect that the common Lys103Asn mutation in HIV-1 reverse transcriptase (RT) has on the binding of three representative non-nucleoside RT inhibitors (NNRTI), nevirapine, efavirenz, and etravirine. 2005 Journal of the American Chemical Society Abstract HIV K103N 125 134 RT;NNRTI;RT;RT 153;253;176;238 174;258;178;240 15902696 Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients. In addition, five genotypes harboring K65R with TAMs or L74V mutation were observed at failure. 2005 Journal of medical virology Abstract HIV K65R;L74V 38;56 42;60 15902696 Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients. The K65R mutation can emerge even with TAMs or L74V. 2005 Journal of medical virology Abstract HIV K65R;L74V 4;47 8;51 15902696 Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients. The K65R mutation, absent from all baseline genotypes, developed in 19 of the 96 patients, with an incidence significantly higher in group II than in group I. 2005 Journal of medical virology Abstract HIV K65R 4 8 15902696 Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients. The selection of K65R was closely linked to the absence of TAMs at baseline and to the regimens sparing both protease inhibitors (PIs) and non-NRTIs. 2005 Journal of medical virology Abstract HIV K65R 17 21 NNRTI;PR;PI 139;109;130 148;117;133 15905682 A therapy-related point mutation changes the HLA restriction of an HIV-1 Pol epitope from A2 to B57 and enhances its recognition. In this study, we investigated CD8 T-cell recognition of wild-type HIV-1 Pol (RT 210-220) peptide LRWGFTTPDKK and of several variants incorporating common antiretroviral therapy-associated mutations (L210W, T215Y, Y215C). 2005 AIDS (London, England) Abstract HIV L210W;T215Y;Y215C 200;207;214 205;212;219 Pol;RT 73;78 76;80 15905975 Highly conserved beta16/beta17 beta-hairpin structure in human immunodeficiency virus type 1 YU2 gp120 is critical for CCR5 binding. Substitution of amino acid residues like E381A did not affect gp120 binding to CD4 and did not induce significant structural changes in gp120, as demonstrated by epitope analysis, BIACORE analysis, and circular dichroism. 2005 Journal of molecular medicine (Berlin, Germany) Abstract HIV E381A 41 46 gp120;gp120 62;136 67;141 15906447 [Treatment strategies for human immunodeficiency virus infection or "return to the future"]. Accordingly, the first antiretroviral drug available zidovudine, after being left over for some time, now is an active component of tritherapies because of its ability to reduce the emergence of the K65R resistance mutation induced by some nucleosidic reverse transcriptase inhibitors. 2004 Medecine et maladies infectieuses Abstract HIV K65R 199 203 RT 252 273 15910811 2H-Pyrrolo[3,4-b] [1,5]benzothiazepine derivatives as potential inhibitors of HIV-1 reverse transcriptase. Unfortunately, none of the test compounds inhibited the multiplication of clinically relevant drug-resistant viruses (mutants of HIV-1 carrying K103N and Y181C mutations) at concentrations lower than 30 microM. 2005 Farmaco (Societa chimica italiana Abstract HIV K103N;Y181C 144;154 149;159 15911424 Genotypic resistance analyses in nucleoside-pretreated patients failing an indinavir containing regimen: results from a randomized comparative trial: (Novavir ANRS 073). At time to failure, mutation M184V in the RT gene was present in 22 out of the 27 failing patients. 2005 Journal of clinical virology Abstract HIV M184V 29 34 RT 42 44 15916425 Synthesis, antiviral activity, and mechanism of drug resistance of D- and L-2',3'-didehydro-2',3'-dideoxy-2'-fluorocarbocyclic nucleosides. Also, like other L-nucleosides, the unfavorable steric hindrance of the sugar moiety of L-2'F-C-d4A and the side chain of Val184 could explain the cross-resistance of L-2'F-C-d4A with the M184V mutant. 2005 Journal of medicinal chemistry Abstract HIV M184V 188 193 15916438 Structure-based design, parallel synthesis, structure-activity relationship, and molecular modeling studies of thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriptase inhibitor isosteres of phenethylthiazolylthiourea derivatives. Nevertheless, the fold increase in resistance of 41 was not greater than that of efavirenz against the K103R mutant in enzyme assays. 2005 Journal of medicinal chemistry Abstract HIV K103R 103 108 15916438 Structure-based design, parallel synthesis, structure-activity relationship, and molecular modeling studies of thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriptase inhibitor isosteres of phenethylthiazolylthiourea derivatives. TCs 31, 37, 39, 40, and 44 significantly reduced the multiplication of the Y181C mutant, but they were inactive against K103R and K103N + Y181C mutants. 2005 Journal of medicinal chemistry Abstract HIV K103N;K103R;Y181C;Y181C 130;120;75;138 135;125;80;143 15917239 Alanine scanning mutants of the HIV gp41 loop. the G597A and S618A mutants are relatively conservative substitutions) suggests that this association is an attractive and novel target for future drug discovery efforts. 2005 The Journal of biological chemistry Abstract HIV G597A;S618A 4;14 9;19 15917239 Alanine scanning mutants of the HIV gp41 loop. The reduced functionality of many mutants was apparently due to either disruption of envelope processing (L593A and T606A), viral incorporation of the envelope (W610A, W614A, and I662A), or increased dissociation of gp120 (W596A, G597A, and S618A). 2005 The Journal of biological chemistry Abstract HIV G597A;I662A;L593A;S618A;T606A;W596A;W610A;W614A 230;179;106;241;116;223;161;168 235;184;112;246;121;228;166;173 Env;Env;gp120 85;151;216 93;159;221 15917239 Alanine scanning mutants of the HIV gp41 loop. With respect to the wild-type gp41, mutational effects on viral entry fall into four classes as follows: 1) little or no effect (G594A, S599A, G600A, K601A, N611A, S615A, N616A, and L619A); 2) significantly reduced entry (I595A, L602A, I603A, V608A, and K617A); 3) abolished entry (L593A, W596A, G597A, T606A, W610A, W614A, S618A, and I622A); and 4) enhanced entry (T605A, P609A, S613A, E620A, and Q621A). 2005 The Journal of biological chemistry Abstract HIV E620A;G594A;G597A;G600A;I595A;I603A;I622A;K601A;K617A;L593A;L602A;L619A;N611A;N616A;P609A;Q621A;S599A;S613A;S615A;S618A;T605A;T606A;V608A;W596A;W610A;W614A 387;129;296;143;222;236;335;150;254;282;229;182;157;171;373;398;136;380;164;324;366;303;243;289;310;317 392;134;301;148;227;241;340;155;259;287;234;187;162;176;378;403;141;385;169;329;371;308;248;294;315;322 gp41 30 34 15917527 TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. In sequential passage experiments using HIV-1 LAI, two mutations (R41T and K70E) were selected. 2005 Antimicrobial agents and chemotherapy Abstract HIV K70E;R41T 75;66 79;71 15919889 Suppression of virus load by highly active antiretroviral therapy in rhesus macaques infected with a recombinant simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. The virus load in one of these two animals rebounded; virus from this animal was initially free of drug-resistance mutations but acquired the K65R mutation in reverse transcriptase at 11 weeks after efavirenz treatment was withdrawn. 2005 Journal of virology Abstract HIV K65R 142 146 RT 159 180 15919925 Induction of T-cell immunity to antiretroviral drug-resistant human immunodeficiency virus type 1. Novel CD8 T-cell responses were detected against the common L63P and L10I protease inhibitor fitness mutations. 2005 Journal of virology Abstract HIV L10I;L63P 69;60 73;64 PR 74 82 15929708 Enfuvirtide binding domain is highly conserved in non-B HIV type 1 strains from Cameroon, West Central Africa. Other common substitutions like Q40H and N42T were also absent. 2005 AIDS research and human retroviruses Abstract HIV N42T;Q40H 41;32 45;36 15929708 Enfuvirtide binding domain is highly conserved in non-B HIV type 1 strains from Cameroon, West Central Africa. The N42S polymorphism was present in 148 (80.4%) strains. 2005 AIDS research and human retroviruses Abstract HIV N42S 4 8 15933559 Pharmacokinetics of didanosine and drug resistance mutations in infants exposed to zidovudine during gestation or postnatally and treated with didanosine or zidovudine in the first three months of life. The most common ZDV mutation noted at baseline was the T215Y/F (n = 7) mutation; 2 of these infants also had the M41L mutation, which is associated with high level ZDV resistance. 2005 The Pediatric infectious disease journal Abstract HIV M41L;T215F;T215Y 113;55;55 117;62;62 15937277 Structural analysis of an HIV-1 protease I47A mutant resistant to the protease inhibitor lopinavir. In the mutant I47A PR-SQV complexes, the PR flaps are packed more tightly around SQV than in the WT complex, resulting in the formation of additional hydrogen bonds that increase binding affinity of SQV consistent with phenotypic hypersusceptibility. 2005 Protein science Abstract HIV I47A 14 18 PR;PR 19;41 21;43 15937277 Structural analysis of an HIV-1 protease I47A mutant resistant to the protease inhibitor lopinavir. Phenotypic data obtained for five I47A mutants showed unexpected resistance to LPV (86- to >110-fold) and hypersusceptibility to SQV (0.1- to 0.7-fold). 2005 Protein science Abstract HIV I47A 34 38 15937277 Structural analysis of an HIV-1 protease I47A mutant resistant to the protease inhibitor lopinavir. The I47A mutation was found in 99 of 112,198 clinical specimens genotyped after LPV became available in late 2000, but in none of 24,426 clinical samples genotyped from 1998 to October 2000. 2005 Protein science Abstract HIV I47A 4 8 15937277 Structural analysis of an HIV-1 protease I47A mutant resistant to the protease inhibitor lopinavir. We have identified a rare HIV-1 protease (PR) mutation, I47A, associated with a high level of resistance to the protease inhibitor lopinavir (LPV) and with hypersusceptibility to the protease inhibitor saquinavir (SQV). 2005 Protein science Abstract HIV I47A 56 60 PR;PR;PR;PR 32;112;183;42 40;120;191;44 15942889 Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. By sequence analysis, 40 women had no detectable resistance mutations, and an additional 6 women were negative for Y181C after SD-NVP. 2005 The Journal of infectious diseases Abstract HIV Y181C 115 120 15942889 Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. Clonal sequencing confirmed K103N in 5 of 5 representative samples and Y181C in 4 of 4 samples. 2005 The Journal of infectious diseases Abstract HIV K103N;Y181C 28;71 33;76 15942889 Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. Four of the 5 women with newly identified Y181C also had K103N. 2005 The Journal of infectious diseases Abstract HIV K103N;Y181C 57;42 62;47 15942889 Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. Using sensitive real-time polymerase chain reaction assays for the K103N and Y181C resistance mutations, we tested genotyped virus before and after SD-NVP in 50 South African women infected with HIV-1 subtype C. 2005 The Journal of infectious diseases Abstract HIV K103N;Y181C 67;77 72;82 Pol 26 36 15942889 Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated. We found K103N in 16 (40%) of 40 women and Y181C in 5 (11%) of 46 women at 6-36 weeks postpartum. 2005 The Journal of infectious diseases Abstract HIV K103N;Y181C 9;43 14;48 15942890 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. CONCLUSIONS: K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. 2005 The Journal of infectious diseases Abstract HIV K103N 13 18 15942890 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. K103N was also detected in those samples by use of the TyHRT assay. 2005 The Journal of infectious diseases Abstract HIV K103N 0 5 15942890 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. K103N was not detected by ViroSeq 12-24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. 2005 The Journal of infectious diseases Abstract HIV K103N 0 5 15942890 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. 2005 The Journal of infectious diseases Abstract HIV K103N 20 25 15942890 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. RESULTS: ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. 2005 The Journal of infectious diseases Abstract HIV K103N 30 35 15942890 Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP. 2005 The Journal of infectious diseases Abstract HIV K103N 18 23 15943470 Anti-HIV activity of (-)-(2R,4R)-1- (2-hydroxymethyl-1,3-dioxolan-4-yl)-thymine against drug-resistant HIV-1 mutants and studies of its molecular mechanism. (-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). 2005 Journal of medicinal chemistry Abstract HIV D67N;K219Q;K70R;T215Y;K65R;M184V 230;246;235;240;265;288 234;251;239;245;269;293 NRTI 185 189 15943576 Genetic linkage of nevirapine resistance mutations in HIV type 1 seven days after single-dose nevirapine. Different combinations of NVPR mutations were linked in individual clones, but none of the clones contained both K103N and Y181C. 2005 AIDS research and human retroviruses Abstract HIV K103N;Y181C 113;123 118;128 15943576 Genetic linkage of nevirapine resistance mutations in HIV type 1 seven days after single-dose nevirapine. K103N and Y181C were the most common mutations detected. 2005 AIDS research and human retroviruses Abstract HIV Y181C;K103N 10;0 15;5 15949383 [Efficacy of anti-HIV treatment and drug-resistance mutations in some parts of China]. In addition, intermediate level and low level resistance against NRTIs caused by K65R and L74V can also be found, but less commonly. 2005 Zhonghua yi xue za zhi Abstract HIV K65R;L74V 81;90 85;94 NRTI 65 70 15949383 [Efficacy of anti-HIV treatment and drug-resistance mutations in some parts of China]. K103N is the most common mutation against NNRTIs, which can cause high-level resistance to each of the available NNRTIs. 2005 Zhonghua yi xue za zhi Abstract HIV K103N 0 5 NNRTI;NNRTI 42;113 48;119 15949383 [Efficacy of anti-HIV treatment and drug-resistance mutations in some parts of China]. Y181C is another common mutation occurred in Henan cohort, which causes crossing drug resistance and multi-drug resistance to NNRTIs. 2005 Zhonghua yi xue za zhi Abstract HIV Y181C 0 5 NNRTI 126 132 15961674 The role of Thr139 in the human immunodeficiency virus type 1 reverse transcriptase sensitivity to (+)-calanolide A. (+)-Calanolide A lost inhibitory activity (up to 20-fold) against the mutant T139Y, T139Q, T139K, and T139I enzymes. 2005 Molecular pharmacology Abstract HIV T139I;T139K;T139Q;T139Y 102;91;84;77 107;96;89;82 15961674 The role of Thr139 in the human immunodeficiency virus type 1 reverse transcriptase sensitivity to (+)-calanolide A. (+)-Calanolide A, the most potent compound of this class, selects for the T139I resistance mutation in HIV-1 reverse transcriptase (RT). 2005 Molecular pharmacology Abstract HIV T139I 74 79 RT;RT 109;132 130;134 15961674 The role of Thr139 in the human immunodeficiency virus type 1 reverse transcriptase sensitivity to (+)-calanolide A. Mutant T139K, T139D, and T139Y RTs had seriously impaired catalytic activities. 2005 Molecular pharmacology Abstract HIV T139D;T139K;T139Y 14;7;25 19;12;30 RT 31 34 15961674 The role of Thr139 in the human immunodeficiency virus type 1 reverse transcriptase sensitivity to (+)-calanolide A. The fact that the T139I RT 1) proved to be resistant to (+)-calanolide A, 2) represents a catalytically efficient enzyme, and 3) requires only a single transition point mutation (ACA-->ATA) in codon 139 seems to explain why mutant T139I RT virus strains, but not virus strains containing other amino acid changes at this position, predominantly emerge in cell cultures under (+)-calanolide A pressure. 2005 Molecular pharmacology Abstract HIV C139T;T139I;T139I 178;18;231 202;23;236 RT;RT 24;237 26;239 15961674 The role of Thr139 in the human immunodeficiency virus type 1 reverse transcriptase sensitivity to (+)-calanolide A. The mutant T139Q enzyme retained full catalytic activity compared with wild-type RT, whereas the mutant T139I, T139S, and T139A RTs retained only 85 to 50% of the activity. 2005 Molecular pharmacology Abstract HIV T139A;T139I;T139Q;T139S 122;104;11;111 127;109;16;116 RT;RT 81;128 83;131 15961674 The role of Thr139 in the human immunodeficiency virus type 1 reverse transcriptase sensitivity to (+)-calanolide A. The mutations in the T139I and T139D RTs were shown to destabilize the RT heterodimer. 2005 Molecular pharmacology Abstract HIV T139D;T139I 31;21 36;26 RT;RT 37;71 40;73 15965076 Identification of three mutations in the Cu,Zn-superoxide dismutase (Cu,Zn-SOD) gene with familial amyotrophic lateral sclerosis: transduction of human Cu,Zn-SOD into PC12 cells by HIV-1 TAT protein basic domain. In undifferentiated PC12 cells, wild-type Tat-SOD1 could prevent DNA fragmentation due to superoxide anion attacks generated by 35 mM paraquat, whereas mutant Tat-D101G enhanced cell death. 2005 Annals of the New York Academy of Sciences Abstract HIV D101G 163 168 Tat;Tat 42;159 45;162 15965076 Identification of three mutations in the Cu,Zn-superoxide dismutase (Cu,Zn-SOD) gene with familial amyotrophic lateral sclerosis: transduction of human Cu,Zn-SOD into PC12 cells by HIV-1 TAT protein basic domain. Three point mutations, E21K, D90V, and D101G, were cloned by site-directed mutagenesis and showed lower SOD1 activity. 2005 Annals of the New York Academy of Sciences Abstract HIV D101G;D90V;E21K 39;29;23 44;33;27 15970587 The 3'-azido group is not the primary determinant of 3'-azido-3'-deoxythymidine (AZT) responsible for the excision phenotype of AZT-resistant HIV-1. The results indicate that mutations correlated with resistance to AZT (D67N/K70R/T215F/K219Q) confer resistance to the 3'-azidopyrimidine nucleosides (AZddC, AZT, and AZddU) but not to the 3'-azidopurine nucleosides (AZddA and AZddG). 2005 The Journal of biological chemistry Abstract HIV D67N;K219Q;K70R;T215F 71;87;76;81 75;92;80;86 15974590 Novel 1-[2-(diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles as HIV-1 non-nucleoside reverse transcriptase inhibitors. A structure-activity relationship investigation. Compounds 7 (ID(50) = 8.25 microM) were found more active than efavirenz (ID(50) = 25 microM) against the viral RT carrying the K103N mutation, suggesting for these compounds a potential use in efavirenz based anti-AIDS regimens. 2005 Journal of medicinal chemistry Abstract HIV K103N 128 133 RT 112 114 AIDS 215 219 15977236 Subtype analysis and mutations to antiviral drugs in HIV-1-infected patients from Mozambique before initiation of antiretroviral therapy: results from the DREAM programme. In Protease (PR), V82I (10.3%) is the only relevant mutation, while natural polymorphisms/secondary mutations are found, some at very high frequency: 20R (25.9%), 36I (91.4%), 36L (8.6%), 60E (31.0%), 63P (29.3%), and 93L (96.6%). 2005 Journal of medical virology Abstract HIV V82I 18 22 PR;PR 3;13 11;15 15977236 Subtype analysis and mutations to antiviral drugs in HIV-1-infected patients from Mozambique before initiation of antiretroviral therapy: results from the DREAM programme. The pattern of covariation observed for K20R and D60E (but not L63P and M36I) was different between C and B subtype isolates from PR-inhibitor-treated patients. 2005 Journal of medical virology Abstract HIV D60E;K20R;L63P;M36I 49;40;63;72 53;44;67;76 PR 130 132 15977242 Diverse pattern of protease inhibitor resistance mutations in HIV-1 infected patients failing nelfinavir. A surprisingly diverse pattern of primary PI mutations was seen: M46I (n=7), D30N (n=6), L90M (n=5), and V82A (n=4). 2005 Journal of medical virology Abstract HIV D30N;L90M;M46I;V82A 77;89;65;105 81;93;69;109 PI 42 44 15977242 Diverse pattern of protease inhibitor resistance mutations in HIV-1 infected patients failing nelfinavir. At baseline, the V82A mutation was found in four PI-naive patients of whom two failed therapy exhibiting this mutation. 2005 Journal of medical virology Abstract HIV V82A 17 21 PI 49 51 15977242 Diverse pattern of protease inhibitor resistance mutations in HIV-1 infected patients failing nelfinavir. Patients who fail NFV may develop the M46I mutation, which has been related earlier to mainly other PI. 2005 Journal of medical virology Abstract HIV M46I 38 42 PI 100 102 15977242 Diverse pattern of protease inhibitor resistance mutations in HIV-1 infected patients failing nelfinavir. The diverse pattern of the evolved PI-mutations and the relative low occurrence of the D30N mutation in the material was unexpected and did not seem to be related to the viral subtype. 2005 Journal of medical virology Abstract HIV D30N 87 91 PI 35 37 15980332 The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. By contrast, the L74V mutation, which confers resistance to didanosine, sensitizes HIV-1 to AZT and partially restores AZT susceptibility when present together with one or more TAMs. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V 17 21 15980332 The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. The presence of 74V in an otherwise wild-type RT reduced the rate of primer unblocking to a degree similar to that observed with the M184V mutation for lamivudine resistance, which also sensitizes HIV-1 to AZT. 2005 Antimicrobial agents and chemotherapy Abstract HIV M184V 133 138 RT 46 48 15980332 The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. These results demonstrate that L74V enhances AZT susceptibility by reducing the extent of its removal by ATP-dependent phosphorolysis and provides further evidence for a common mechanism by which mutations conferring resistance to didanosine and lamivudine sensitize HIV-1 to AZT. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V 31 35 15980332 The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. To compare rates of primer unblocking in RTs carrying different clusters of TAMs and to explore the biochemical mechanism by which L74V affects AZT susceptibility, ATP-mediated rescue of AZT-blocked DNA synthesis was assayed using a series of purified recombinant RTs. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V 131 135 RT;RT 41;264 44;267 15980333 Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. Finally, we confirmed previous findings that L74V-containing viruses display diminished replication capacity and that this is associated with reduced levels of synthesis of early reverse-transcribed viral DNA molecules. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V 45 49 15980333 Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. In addition, we determined that the L74V and M184V mutations did not affect the ratio between the populations of RT-DNA/DNA complexes found at pre- and posttranslocational stages; however, they might have affected proper alignment between incorporated chain terminator and pyrophosphate donor, substrate orientation, affinity for ATP, and/or primer-template substrate. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V;M184V 36;45 40;50 RT 113 115 15980333 Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. The L74V and M184V mutations in the reverse transcriptase (RT) gene of human immunodeficiency virus type 1 (HIV-1) are frequently associated with resistance to the nucleoside reverse transcriptase inhibitors abacavir, didanosine, and lamivudine. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V;M184V 4;13 8;18 NRTI;RT;RT 164;36;59 196;57;61 15980333 Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. To understand the biochemical mechanisms responsible for the hypersensitization of L74V-containing viruses to ZDV, we studied the efficiency of excision of ZDV-monophosphate (ZDV-MP)-terminated primers by recombinant wild-type and mutated HIV-1 RTs in cell-free assays. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V 83 87 RT 245 248 15980333 Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. We observed that the L74V mutation in RT caused reductions in ATP-dependent removal of ZDV-MP from newly synthesized viral DNA. 2005 Antimicrobial agents and chemotherapy Abstract HIV L74V 21 25 RT 38 40 15983922 Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. Available data suggest that lamivudine contributes to partial viral suppression, despite the presence of M184V mutations and high-level phenotypic lamivudine resistance. 2005 Clinical infectious diseases Abstract HIV M184V 105 110 15983922 Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. CONCLUSIONS: In select cases of multidrug-resistant HIV-1 infection, lamivudine contributes to suppression of HIV-1 replication, despite the presence of M184V mutations and lamivudine resistance. 2005 Clinical infectious diseases Abstract HIV M184V 153 158 HIV infections 52 67 15983922 Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. Early increases in plasma levels of HIV-1 RNA after lamivudine withdrawal were associated with the presence of the T215Y/F mutation and broad phenotypic resistance to nucleoside reverse-transcriptase inhibitors at baseline. 2005 Clinical infectious diseases Abstract HIV T215F;T215Y 115;115 122;122 NRTI 167 199 15990579 Lack of resistant mutation development after receiving short-course zidovudine plus lamivudine to prevent mother-to-child transmission. One of the three infected infants carried the M184V and K219Q mutations. 2005 AIDS (London, England) Abstract HIV K219Q;M184V 56;46 61;51 15992850 Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein. However, both the I166A mutation and the V1 deletion of gp135 increased cell-to-cell fusion activity and binding of Mab F7-299 to the oligomeric Env. 2005 Virology Abstract HIV I166A 18 23 Env 145 148 15992850 Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein. Mutation of isoleucine-166 to alanine in the putative loop B of gp135 increased the affinity of soluble gp135 for the CAEV receptor(s) and goat monoclonal antibody (Mab) F7-299 which recognizes an epitope overlapping the gp135 RBS. 2005 Virology Abstract HIV I166A 12 37 15992850 Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein. The I166A mutation also stabilized or exposed the F7-299 epitope in anionic detergent buffers, indicating that the I166A mutation induces conformational changes and stabilizes the RBS of soluble gp135 and enhances Mab F7-299 binding. 2005 Virology Abstract HIV I166A;I166A 4;115 9;120 15992850 Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein. Therefore, the CAEV gp135 RBS is protected from antibody binding by mechanisms both dependent and independent of Env oligomerization which are disrupted by the V1 deletion and the I166A mutation, respectively. 2005 Virology Abstract HIV I166A 180 185 Env 113 116 15994775 Evaluating the immunogenicity of a disulfide-stabilized, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. In this construct, the gp120 and gp41 moieties are covalently linked by an intermolecular disulfide bond (SOS gp140), and an I559P substitution has been added to stabilize gp41-gp41 interactions (SOSIP gp140). 2005 Journal of virology Abstract HIV I559P 125 130 gp120;gp140;gp140;gp41;gp41;gp41 23;110;202;33;172;177 28;115;207;37;176;181 16005679 Defective rev response element (RRE) and rev gene in HAART treated AIDS patients with discordance between viral load and CD4+ T-cell counts. In another patients, Rev synthesis was prematurely stopped due to G135T substitution in the amino terminal domain. 2005 Journal of clinical virology Abstract HIV G135T 66 71 Rev 21 24 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). All three nucleoside analogs are known to select the K65R and/or M184V/I mutation. 2005 Journal of virology Abstract HIV K65R;M184I;M184V 53;65;65 57;72;72 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). At W12, M184V/I was found in 18/20 patient, together with the K65R in 13 patients. 2005 Journal of virology Abstract HIV K65R;M184I;M184V 62;8;8 66;15;15 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). At W12, the K65R mutation was found in 30 to 100% of clones. 2005 Journal of virology Abstract HIV K65R 12 16 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). At W4, clonal analysis revealed the K65R mutation in 0.6 to 48% of clones in the five patients studied. 2005 Journal of virology Abstract HIV K65R 36 40 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). At W4, M184V/I was detected in 12/19 patients and K65K/R in 2 patients by bulk sequencing. 2005 Journal of virology Abstract HIV K65K;K65R;M184I;M184V 50;50;7;7 56;56;14;14 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). However, K65R was also detected early using a clone-sensitive genotyping method. 2005 Journal of virology Abstract HIV K65R 9 13 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). K65R and M184V/I seemed to arise in separate clones, followed by an enrichment of viruses containing both mutations. 2005 Journal of virology Abstract HIV M184I;M184V;M184V;K65R 9;9;9;0 16;18;16;4 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). M184V/I was selected more frequently than K65R at W4. 2005 Journal of virology Abstract HIV K65R;M184I;M184V 42;0;0 46;7;7 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). The objective of this study was to examine the selection dynamics of the K65R and M184V/I mutations. 2005 Journal of virology Abstract HIV K65R;M184I;M184V 73;82;82 77;89;89 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). The RT genes from baseline, W4, and W12 plasma samples from five patients who developed both M184V and K65R but with different mutational patterns were also cloned and screened for the K65R mutation by selective real-time PCR. 2005 Journal of virology Abstract HIV K65R;K65R;M184V 103;185;93 107;189;98 RT 4 6 16014919 Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). There was a high rate of early virological failure, and the M184V and K65R mutations were frequently detected at week 12 (W12). 2005 Journal of virology Abstract HIV K65R;M184V 70;60 74;65 16014956 Soluble mimetics of human immunodeficiency virus type 1 viral spikes produced by replacement of the native trimerization domain with a heterologous trimerization motif: characterization and ligand binding analysis. To further examine restricted CD4 stoichiometric binding to the gp120-GCN4 trimers, we generated a low-affinity CD4 binding trimer by introducing a D457V change in the CD4 binding site of each gp120 monomeric subunit. 2005 Journal of virology Abstract HIV D457V 148 153 gp120;gp120 64;193 69;198 16038473 Comparison of tests and procedures to build clinically relevant genotypic scores: application to the Jaguar study. RESULTS: Eight mutations were associated with a reduced virological response to ddI: M41L, D67N, T69D, L74V, V1181, L210W, T215Y/F and K219Q/E and two mutations with a better virological response: K70R and M184V/I. 2005 Antiviral therapy Abstract HIV D67N;K219E;K219Q;K70R;L210W;L74V;M184I;M184V;M41L;T215F;T215Y;T69D 91;135;135;197;116;103;206;206;85;123;123;97 95;142;142;201;121;107;213;213;89;130;130;101 16038473 Comparison of tests and procedures to build clinically relevant genotypic scores: application to the Jaguar study. The Jonckheere-Terpstra test for trend provided the combination of mutations (M41L+T69D-K70R+L74V-M184V /I+T215Y/F+ K219A/E) that were the most predictive for the week 4 virological response, that is, leading to the lowest P value. 2005 Antiviral therapy Abstract HIV K219A;K219E;K70R;L74V;M184V;M41L;T215F;T215Y;T69D 116;116;88;93;98;78;107;107;83 123;123;92;97;103;82;114;114;87 16044009 Outbreak of a West African recombinant of HIV-1 in Tashkent, Uzbekistan. Most of these subtype A-infected drug-naive subjects (65.6%) had an accessory drug resistance mutation, A62V, in the reverse transcriptase gene. 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V 104 108 RT 117 138 16048944 Quantifying mixed populations of drug-resistant human immunodeficiency virus type 1. For cDNA, nucleotide polymorphisms for codon M184V (ATG to GTG) and K65R (AAA to AGA) could be differentiated and quantified even when the population mixture varied as much as 1 to 10,000. 2005 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V 68;45 72;50 16048947 Anti-human immunodeficiency virus type 1 activity and resistance profile of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine in vitro. Analysis of 4'-Ed4T-resistant HIV-1 obtained through in vitro selection revealed that the virus was also resistant to 3TC and had two amino acid mutations (P119S and T165A) in addition to the M184V mutation. 2005 Antimicrobial agents and chemotherapy Abstract HIV M184V;P119S;T165A 192;156;166 197;162;171 16048947 Anti-human immunodeficiency virus type 1 activity and resistance profile of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine in vitro. Approximately 6- to 11-fold decreases in susceptibility to 4'-Ed4T were observed for HIV-1 carrying NRTI-associated mutations (D67N, K70R, T215F, and K219Q) or the lamivudine (3TC)-resistant mutation M184V. 2005 Antimicrobial agents and chemotherapy Abstract HIV D67N;K219Q;K70R;M184V;T215F 127;150;133;200;139 131;155;137;205;144 NRTI 100 104 16048947 Anti-human immunodeficiency virus type 1 activity and resistance profile of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine in vitro. Furthermore, the activity of 4'-Ed4T appeared to be enhanced in the presence of K103N, a major nonnucleoside reverse transcriptase inhibitor-resistant mutation. 2005 Antimicrobial agents and chemotherapy Abstract HIV K103N 80 85 NNRTI 95 130 16048947 Anti-human immunodeficiency virus type 1 activity and resistance profile of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine in vitro. In contrast, the susceptibility of the virus carrying the K65R mutation or the multidrug-resistant mutation with the Q151M complex (A62V, V75I, F77L, F116Y, and Q151M) was not altered. 2005 Antimicrobial agents and chemotherapy Abstract HIV A62V;F116Y;F77L;K65R;Q151M;Q151M;V75I 132;150;144;58;117;161;138 136;155;148;62;122;166;142 16051814 Formaldehyde-treated, heat-inactivated virions with increased human immunodeficiency virus type 1 env can be used to induce high-titer neutralizing antibody responses. Thus, a clade B vaccine which contains a single point mutation in gp41 (Y706C) that results in increased incorporation of oligomeric Env into virions was constructed. 2005 Journal of virology Abstract HIV Y706C 72 77 gp41;Env 66;133 70;136 16051817 Determinants of human immunodeficiency virus type 1 resistance to membrane-anchored gp41-derived peptides. For HIV-1(NL4-3) a single amino acid change at position 33 in HR1 (L33S) was selected, whereas for HIV-1(BaL) the majority of the sequences obtained showed two amino acid changes, one in HR1 and one in HR2 (I48V/N126K). 2005 Journal of virology Abstract HIV I48V;L33S;N126K 207;67;212 211;71;217 16051817 Determinants of human immunodeficiency virus type 1 resistance to membrane-anchored gp41-derived peptides. Replication capacity and dual-color competition assays revealed that the double mutation I48V/N126K in HIV-1(BaL) results in a strong reduction of viral fitness, whereas the L33S mutation in HIV-1(NL4-3) did enhance viral fitness compared to the respective parental viruses. 2005 Journal of virology Abstract HIV I48V;L33S;N126K 89;174;94 93;178;99 16051818 Mutations that abrogate human immunodeficiency virus type 1 reverse transcriptase dimerization affect maturation of the reverse transcriptase heterodimer. Steady-state levels of the p66 and p51 RT subunits in viral lysates of the W401L and W401A mutants were reduced, but no significant decrease in Gag-Pol was observed compared to the wild type. 2005 Journal of virology Abstract HIV W401A;W401L 85;75 90;80 GagPol;RT 144;39 151;41 16051818 Mutations that abrogate human immunodeficiency virus type 1 reverse transcriptase dimerization affect maturation of the reverse transcriptase heterodimer. The introduction of the RT dimerization-inhibiting mutations W401L and W401A into HIV-1 resulted in the formation of noninfectious viruses with reduced levels of both virion-associated and intracellular RT activity compared to the wild-type virus and the W401F mutant, which does not inhibit RT dimerization in vitro. 2005 Journal of virology Abstract HIV W401A;W401F;W401L 71;255;61 76;260;66 RT;RT;RT 24;203;292 26;205;294 16051828 Genetic analyses of conserved residues in the carboxyl-terminal domain of human immunodeficiency virus type 1 integrase. Because single-round HIV-1(E246K.Luc(R-)) transduced cells at approximately 8% of the wild-type level, we concluded that the late-stage processing defect contributed significantly to the overall replication defect of HIV-1(E246K). 2005 Journal of virology Abstract HIV E246K;E246K 27;223 32;228 16051828 Genetic analyses of conserved residues in the carboxyl-terminal domain of human immunodeficiency virus type 1 integrase. In contrast, replication-defective HIV-1(E246K) synthesized near-normal cDNA levels but processing of Pr55(gag) was largely inhibited in virus-producing cells. 2005 Journal of virology Abstract HIV E246K 41 46 Gag;PR 107;102 110;104 16053762 [Genotypic antiretroviral resistance testing and phylogenetic analysis of protease and reverse transcriptase in antiretroviral drug-naive AIDS patients in Henan province]. Minor mutation rate of resistance was 100%, including types of L63PS (36/36), I93L (35/36), V77IL (34/36), A71IVT (10/36) and D60E (2/36). 2005 Zhonghua liu xing bing xue za zhi Abstract HIV A71I;A71T;A71V;D60E;I93L;L63P;L63S;V77I;V77L 107;107;107;126;78;63;63;92;92 113;113;113;130;82;68;68;97;97 16053762 [Genotypic antiretroviral resistance testing and phylogenetic analysis of protease and reverse transcriptase in antiretroviral drug-naive AIDS patients in Henan province]. The major mutation rate of resistance to protease was 8.3% (3/36), including types D30A, V32A, G73C and V82A. 2005 Zhonghua liu xing bing xue za zhi Abstract HIV D30A;G73C;V32A;V82A 83;95;89;104 87;99;93;108 PR 41 49 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. In our recent studies, MT-4/17-3-6, a strain of HIV-1, showed the strong resistance to peptide fusion inhibitors compared with other strains such as MT-4/LAI, L-2 and CU98-26, and had a distinctive L565M mutation in the central region of NHR. 2005 Biochemical and biophysical research communications Abstract HIV L565M 198 203 16060672 Kinetic evidence for interaction of human immunodeficiency virus type 1 reverse transcriptase with the 3'-OH of the incoming dTTP substrate. In contrast, the Q151N and V148I mutants, which were predicted to have lost H-bonding interaction with the 3'-OH of dTTP, showed higher but similar K(d) values for dTTP, ddTTP, and acyTTP. 2005 Biochemistry Abstract HIV Q151N;V148I 17;27 22;32 16060672 Kinetic evidence for interaction of human immunodeficiency virus type 1 reverse transcriptase with the 3'-OH of the incoming dTTP substrate. Interestingly, the Q151N and V148I RTs bound to AZTTP approximately 12 and 18 times more tightly than to dTTP, respectively. 2005 Biochemistry Abstract HIV Q151N;V148I 19;29 24;34 RT 35 38 16060672 Kinetic evidence for interaction of human immunodeficiency virus type 1 reverse transcriptase with the 3'-OH of the incoming dTTP substrate. On the basis of this, we predicted that while wild-type (WT) HIV-1 RT would have decreased binding affinity to dTTP analogues lacking 3'-OH, compared to dTTP, the Q151N and V148I RT mutants should have decreased but similar affinity to both dTTP and dTTP analogues. 2005 Biochemistry Abstract HIV Q151N;V148I 163;173 168;178 RT;RT 67;179 69;181 16060672 Kinetic evidence for interaction of human immunodeficiency virus type 1 reverse transcriptase with the 3'-OH of the incoming dTTP substrate. Structural modeling based on the crystal structure of the HIV-1 RT ternary complex with dTTP proposes that Q151N loses the interaction with the 3'-OH of the incoming dTTP and that V148I disrupts positioning of Q151 for this interaction. 2005 Biochemistry Abstract HIV Q151N;V148I 107;180 112;185 RT 64 66 16060672 Kinetic evidence for interaction of human immunodeficiency virus type 1 reverse transcriptase with the 3'-OH of the incoming dTTP substrate. Two previously identified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutants, Q151N and V148I, are known to have reduced dNTP binding affinity but possess wild-type chemical catalysis rates. 2005 Biochemistry Abstract HIV Q151N;V148I 106;116 111;121 RT;RT 70;93 91;95 16060700 Tipranavir: a ritonavir-boosted protease inhibitor. Analysis of clinical isolates from treatment-experienced patients identified the following tipranavir resistance-associated HIV protease mutations: L10V, I13V, K20M/R/V, L33F, E35G, M36I, K43T, M46L, I47V, I54A/M/V, Q58E, H69K, T74P, V82L/T, N83D, I84V. 2005 Drugs Abstract HIV E35G;H69K;I13V;I47V;I54A;I54M;I54V;I84V;K20M;K20R;K20V;K43T;L10V;L33F;M36I;M46L;N83D;Q58E;T74P;V82L;V82T 176;222;154;200;206;206;206;248;160;160;160;188;148;170;182;194;242;216;228;234;234 180;226;158;204;214;214;214;252;168;168;168;192;152;174;186;198;246;220;232;240;240 PR 128 136 16060830 Treatment response and drug resistance in patients infected with HIV type 1 group O viruses. Another selected mutations K70N, V75A, and M184V at the RT, and D30D/N and I84V at the protease while failing on indinavir. 2005 AIDS research and human retroviruses Abstract HIV D30D;D30N;I84V;K70N;M184V;V75A 64;64;75;27;43;33 70;70;79;31;48;37 PR;RT 87;56 95;58 16060830 Treatment response and drug resistance in patients infected with HIV type 1 group O viruses. One selected changes M41L, E44D, D67N, V75M, M184V, and T215Y at the RT, and G48M, F53L, I54V, V82A, and L90M at the protease. 2005 AIDS research and human retroviruses Abstract HIV D67N;E44D;F53L;G48M;I54V;L90M;M184V;M41L;T215Y;V75M;V82A 33;27;83;77;89;105;45;21;56;39;95 37;31;87;81;93;109;50;25;61;43;99 PR;RT 117;69 125;71 16107158 Novel 8-substituted dipyridodiazepinone inhibitors with a broad-spectrum of activity against HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors. A series of novel 8-substituted dipyridodiazepinone-based inhibitors were investigated for their antiviral activity against wild type human immunodeficiency virus (HIV-1) and the clinically prevalent K103N/Y181C mutant virus. 2005 Journal of medicinal chemistry Abstract HIV K103N;Y181C 200;206 205;211 16107990 Risk of selecting de novo drug-resistance mutations during structured treatment interruptions in patients with chronic HIV infection. Mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs), excluding the M184V mutation, were selected in 2 (6%) of 35 recipients of NRTIs (1 [3%] of these mutations was de novo, and 1 [3%] was an archived mutation. 2005 Clinical infectious diseases Abstract HIV M184V 102 107 NRTI;NRTI;NRTI 35;80;162 67;85;167 16114038 Quantum computational analysis for drug resistance of HIV-1 reverse transcriptase to nevirapine through point mutations. Quantum chemical calculation has been carried out to analyze binding interactions of nevirapine to HIV-1 reverse transcriptase (RT) and single point mutants Lys103 --> Asn (K103N) and Tyr181--> Cys (Y181C). 2005 Proteins Abstract HIV K103N;K103N;Y181C;Y181C 173;157;199;184 178;171;204;197 RT;RT 105;128 126;130 16122817 Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. At the end of the selection experiments, viruses harbouring 10 mutations in the protease (L10F, I13V, V32I, L33F, M36I, K45I, I54V, A71V, V82L, I84V) as well as a mutation in the CA/SP1 gag cleavage site were selected and showed 87-fold decreased susceptibility to tipranavir. 2005 Antiviral research Abstract HIV A71V;I13V;I54V;I84V;K45I;L10F;L33F;M36I;V32I;V82L 132;96;126;144;120;90;108;114;102;138 136;100;130;148;124;94;112;118;106;142 PR;SP1;Gag;Capsid 80;182;186;179 88;185;189;181 16122817 Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Characterization of the selected variants revealed that the first mutations to be selected were L33F and I84V in the viral protease, mutations which together conferred less than two-fold resistance to tipranavir. 2005 Antiviral research Abstract HIV I84V;L33F 105;96 109;100 PR 123 131 16123676 Effect of the Q207D mutation in HIV type 1 reverse transcriptase on zidovudine susceptibility and replicative fitness. Introduction of the Q207D mutation into the RT of a zidovudine (ZDV)-resistant isolate by site-directed mutagenesis increased ZDV resistance 2.7-fold but had no effect on ZDV susceptibility when introduced into wild-type RT. 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q207D 20 25 RT;RT 44;221 46;223 16123677 Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET 012. The higher rate of NVPR in subtype D was explained by at least 2 factors: Y181C faded from detection at a greater rate in women with subtype A (odds ratio = 3.06; 95% CI, 1.04, 8.90) and K103N accumulated at a greater rate in women with subtype D (odds ratio = 1.74; 95% CI, 0.62, 4.87). 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;Y181C 187;74 192;79 16127058 Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones. A unique phenotypic profile has been associated with viruses containing the I50L substitution, which produces ATV-specific resistance and increased susceptibility to most other approved HIV protease inhibitors (PIs). 2005 Antimicrobial agents and chemotherapy Abstract HIV I50L 76 80 PR;PI 190;211 198;214 16127058 Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones. In this report, a direct effect of I50L on the susceptibility to the PI class is described. 2005 Antimicrobial agents and chemotherapy Abstract HIV I50L 35 39 PI 69 71 16127058 Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones. Moreover, the I50L substitution functions to increase PI susceptibility even in the presence of other primary and secondary PI resistance substitutions. 2005 Antimicrobial agents and chemotherapy Abstract HIV I50L 14 18 PI;PI 54;124 56;126 16127058 Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones. Substitution of leucine for isoleucine at residue 50 (I50L) of human immunodeficiency virus (HIV) protease is the signature substitution for atazanavir (ATV) resistance. 2005 Antimicrobial agents and chemotherapy Abstract HIV I50L;I50L 54;16 58;52 PR 98 106 16127058 Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones. The results show that the induction of ATV resistance and increased susceptibility to other PIs by the I50L substitution is likely determined at the level of protease inhibition. 2005 Antimicrobial agents and chemotherapy Abstract HIV I50L 103 107 PR;PI 158;92 166;95 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. Additional biophysical and enzyme kinetics experiments show I50L/A71V protease is a stable enzyme with catalytic activity that is slightly reduced (34%) relative to the WT. 2005 Antimicrobial agents and chemotherapy Abstract HIV A71V;I50L 65;60 69;64 PR 70 78 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. Computational modeling reveals that the unique resistance phenotype of I50L/A71V protease likely originates from bulky tert-butyl groups at P2 and P2' (specific to atazanavir) that sterically clash with methyl groups on residue L50. 2005 Antimicrobial agents and chemotherapy Abstract HIV A71V;I50L 76;71 80;75 PR 81 89 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. Remarkably, we find that all of the PIs have 2- to 10-fold increased affinities for I50L/A71V protease, except for atazanavir. 2005 Antimicrobial agents and chemotherapy Abstract HIV A71V;I50L 89;84 93;88 PR;PI 94;36 102;39 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. The results are also manifested by thermal stability measures of affinity for WT and I50L/A71V proteases. 2005 Antimicrobial agents and chemotherapy Abstract HIV A71V;I50L 90;85 94;89 PR 95 104 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. The results of this study provide a molecular understanding of the novel hypersusceptibility of atazanavir-resistant I50L/A71V-containing clinical isolates to other currently approved PIs. 2005 Antimicrobial agents and chemotherapy Abstract HIV A71V;I50L 122;117 126;121 PI 184 187 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. The signature resistance substitution for atazanavir is I50L, and it is frequently (53%) accompanied by a compensatory A71V substitution that helps restore viability and increases atazanavir resistance levels. 2005 Antimicrobial agents and chemotherapy Abstract HIV A71V;I50L 119;56 123;60 16127059 Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors. We measured the binding affinities of wild-type (WT) and I50L/A71V HIV-1 proteases to atazanavir and other currently approved PIs (ritonavir, lopinavir, saquinavir, nelfinavir, indinavir, and amprenavir) by isothermal titration calorimetry. 2005 Antimicrobial agents and chemotherapy Abstract HIV A71V;I50L 62;57 66;61 PR;PI 73;126 82;129 16127074 In vitro selection and analysis of human immunodeficiency virus type 1 resistant to derivatives of beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine. Serial passage of human immunodeficiency virus type 1 in MT-2 cells in increasing concentrations of the d- and l-enantiomers of beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (d4FC) resulted in the selection of viral variants with reverse transcriptase substitutions M184I or M184V for l-d4FC and I63L, K65R, K70N, K70E, or R172K for d-d4FC. 2005 Antimicrobial agents and chemotherapy Abstract HIV I63L;K65R;K70E;K70N;M184I;M184V;R172K 302;308;320;314;272;281;329 306;312;324;318;277;286;334 RT 236 257 16131488 Nuclear targeting of protein phosphatase-1 by HIV-1 Tat protein. Surprisingly, Tat-Q35R mutant that had a higher affinity for PP1 was also a poor activator of HIV-1 transcription, because strong PP1 binding competed out binding of Tat to CDK9/cyclin T1. 2005 The Journal of biological chemistry Abstract HIV Q35R 18 22 Tat;Tat 14;166 17;169 16131488 Nuclear targeting of protein phosphatase-1 by HIV-1 Tat protein. The PP1 binding mutant Tat-V36A/F38A displayed a decreased affinity for PP1 and was a poor activator of HIV-1 transcription. 2005 The Journal of biological chemistry Abstract HIV F38A;V36A 32;27 36;31 Tat 23 26 16152754 Efficacy and safety of once-daily combination therapy with didanosine, lamivudine and nevirapine in antiretroviral-naive HIV-infected patients. Eight out of nine patients with available genotype after virological failure showed resistance mutations to NVP (Y181C and others) and 3TC (M184V/I), and four of them also had ddI resistance (L74V). 2005 Antiviral therapy Abstract HIV L74V;M184I;M184V;Y181C 192;140;140;113 196;147;147;119 16160186 Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replication. HIV-1(K34A) and related mutants failed to support detectable levels (<1% of wild type) of integration. 2005 Journal of virology Abstract HIV K34A 6 10 16160186 Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replication. HIV-1(K34A) was therefore similar to a number of previously characterized mutant viruses that failed to replicate despite encoding catalytically competent IN. 2005 Journal of virology Abstract HIV K34A 6 10 IN 155 157 16160186 Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replication. We therefore concluded that mutations like K34A disrupted higher-order interactions important for PIC function/maturation compared to the innate catalytic activity of IN enzyme. 2005 Journal of virology Abstract HIV K34A 43 47 IN 167 169 16160186 Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replication. Whereas HIV-1(K46A) grew like the wild type, HIV-1(K34A) was dead. 2005 Journal of virology Abstract HIV K34A;K46A 51;14 55;18 16160186 Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replication. Yet recombinant IN(K34A) protein functioned in in vitro integration assays, and Vpr-IN(K34A) efficiently transcomplemented the infectivity defect of an IN active site mutant virus in cells. 2005 Journal of virology Abstract HIV K34A;K34A 19;87 23;91 Vpr;IN;IN;IN 80;16;84;152 83;18;86;154 16163451 Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs. The investigation about drug resistance for DCK shows no remarkable influence on the most frequently observed mutation K103N of HIV-1 RT. 2005 Journal of computer-aided molecular design Abstract HIV K103N 119 124 RT 134 136 16173024 Analysis of drug resistance-associated mutations in treatment-naive individuals infected with different genetic forms of HIV-1 circulating in countries of the former Soviet Union. V77I substitution in PR was found in 47.8% of samples. 2005 Journal of medical virology Abstract HIV V77I 0 4 PR 21 23 16177107 CD8+ T cell epitope-flanking mutations disrupt proteasomal processing of HIV-1 Nef. These mutations (R69K, A81G, and H87R) flank the HLA B*35-restricted VY8 epitope and persisted to fixation as the early CTL response to this Ag waned. 2005 Journal of immunology (Baltimore, Md. Abstract HIV A81G;H87R;R69K 23;33;17 27;37;21 16183096 The R362A mutation at the C-terminus of CA inhibits packaging of human immunodeficiency virus type 1 RNA. A238T is located within the NTD of CA, G358S and N373K are positioned proximal to R362A. 2005 Virology Abstract HIV G358S;N373K;R362A;A238T 39;49;82;0 44;54;87;5 Capsid 35 37 16183096 The R362A mutation at the C-terminus of CA inhibits packaging of human immunodeficiency virus type 1 RNA. In this study, we identified three second-site mutations within Gag named A238T, G358S, and N373K that rescued a deleterious mutation R362A located at the C-terminus of CA. 2005 Virology Abstract HIV A238T;G358S;N373K;R362A 74;81;92;134 79;86;97;139 Gag;Capsid 64;169 67;171 16183096 The R362A mutation at the C-terminus of CA inhibits packaging of human immunodeficiency virus type 1 RNA. One of the mechanisms underlying this compensation event is correction of reduced packaging of viral RNA into the R362A mutated viruses, as shown by the results of RNase protection assays, native Northern blots experiments as well as filter-binding assays. 2005 Virology Abstract HIV R362A 114 119 16184031 MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells. CONCLUSIONS: Alterations in transepithelial permeability of HIV PI due to the G1199A polymorphism may impact oral bioavailability of PI and penetration into cells and tissues of the lymphoid and central nervous systems. 2005 AIDS (London, England) Abstract HIV G1199A 78 84 PI;PI 64;133 66;135 16184031 MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells. However, the impact of G1199A on P-gp activity appeared to primarily influence drug permeability in the apical-to-basolateral direction. 2005 AIDS (London, England) Abstract HIV G1199A 23 29 16184031 MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells. Kinetic analysis of ritonavir and saquinavir uptake by MDR1wt- and MDR1(1199A)-expressing cells showed that Vmax was similar, while uptake Km was significantly higher in cells expressing the G1199A variant suggesting that alterations in P-gp-dependent efflux mediated by G1199A were due to changes in transporter affinity. 2005 AIDS (London, England) Abstract HIV G1199A;G1199A 191;271 197;277 16184031 MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells. OBJECTIVE: To evaluate the impact of the human multidrug resistance gene (MDR1) G1199A polymorphism (amino acid change Ser400Asn) on P-glycoprotein (P-gp)-dependent transepithelial permeability and uptake kinetics of HIV protease inhibitors (PI), by using recombinant epithelial cells expressing wild-type MDR1 (MDR1wt) or the G1199A variant (MDR1(1199A)). 2005 AIDS (London, England) Abstract HIV G1199A;S400N 327;119 333;128 PR;PI 221;242 229;244 16184042 High rate of virological failure in maintenance antiretroviral therapy with didanosine and tenofovir. At virological failure 'de novo' selected mutations were identified in 11 of the 12 failing patients, including the K65R mutation in seven patients. 2005 AIDS (London, England) Abstract HIV K65R 116 120 16188980 TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. Furthermore, breakthrough of virus from site-directed mutant (SDM) SDM-K103N/Y181C occurred at the same time or later with TMC125 as breakthrough from wild-type HIV-1 with efavirenz or nevirapine. 2005 Journal of virology Abstract HIV K103N;Y181C 71;77 76;82 16188980 TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. The selection experiments identified mutations selected by TMC125 that included known NNRTI-associated mutations L100I, Y181C, G190E, M230L, and Y318F and the novel mutations V179I and V179F. 2005 Journal of virology Abstract HIV G190E;L100I;M230L;V179F;V179I;Y181C;Y318F 127;113;134;185;175;120;145 132;118;139;190;180;125;150 NNRTI 86 91 16189079 Antiviral activity of GW678248, a novel benzophenone nonnucleoside reverse transcriptase inhibitor. An IC(50) of 86 nM was obtained with a mutant virus having V106I, E138K, and P236L mutations that resulted from serial passage of WT virus in the presence of GW678248. 2005 Antimicrobial agents and chemotherapy Abstract HIV E138K;P236L;V106I 66;77;59 71;82;64 16189079 Antiviral activity of GW678248, a novel benzophenone nonnucleoside reverse transcriptase inhibitor. Cytotoxicity studies with GW678248 indicate that the 50% cytotoxicity concentration is greater than the level of compound solubility and provides a selectivity index of >2,500-fold for WT, Y181C, or K103N HIV-1. 2005 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 199;189 204;194 16189079 Antiviral activity of GW678248, a novel benzophenone nonnucleoside reverse transcriptase inhibitor. In HeLa CD4 MAGI cell culture virus replication assays, GW678248 has an IC(50) of < or =21 nM against HIV-1 isogenic strains with single or double mutations known to be associated with NNRTI resistance, including L100I, K101E, K103N, V106A/I/M, V108I, E138K, Y181C, Y188C, Y188L, G190A/E, P225H, and P236L and various combinations. 2005 Antimicrobial agents and chemotherapy Abstract HIV E138K;G190A;G190E;K101E;K103N;L100I;P225H;P236L;V106A;V106I;V106M;V108I;Y181C;Y188C;Y188L 252;280;280;220;227;213;289;300;234;234;234;245;259;266;273 257;287;287;225;232;218;294;305;243;243;243;250;264;271;278 NNRTI 185 190 16191482 Evolution of HIV resistance during treatment interruption in experienced patients and after restarting a new therapy. Appearance of K70R could be explained by a reverse direction of a previously described pathway of thymidin analogues mutation resistance development, while G190A could be due to prolonged subinhibitory drug levels after cessation of NNRTIs. 2005 Journal of clinical virology Abstract HIV G190A;K70R 156;14 161;18 NNRTI 233 239 16191482 Evolution of HIV resistance during treatment interruption in experienced patients and after restarting a new therapy. In two patients new reverse transcriptase associated mutations were detected during TI, G190A (NNRTI mutation) and K70R (NRTI mutation). 2005 Journal of clinical virology Abstract HIV G190A;K70R 88;115 93;119 RT;NNRTI;NRTI 20;95;121 41;100;125 16195257 Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy. Children with I54V and V82A/F had higher prevalence of lopinavir-associated resistance mutations and showed RP of 0.36 (CI95%: 0.17; 0.76; P = 0.007) for achieving uVL. 2005 The Journal of antimicrobial chemotherapy Abstract HIV I54V;V82A;V82F 14;23;23 18;29;29 16195257 Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy. Moreover, I54V and V82A/F led to the poorest virological response. 2005 The Journal of antimicrobial chemotherapy Abstract HIV I54V;V82A;V82F 10;19;19 14;25;25 16195257 Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy. The relative proportion (RP) to uVL was 0.32 (CI95%: 0.16; 0.33; P = 0.002) in children with I54V (46% of total) and 0.48 (CI95%: 0.24; 0.97; P = 0.041) in children with V82A/F (52% of total). 2005 The Journal of antimicrobial chemotherapy Abstract HIV I54V;V82A;V82F 93;170;170 97;176;176 16199531 Naturally occurring capsid substitutions render HIV-1 cyclophilin A independent in human cells and TRIM-cyclophilin-resistant in Owl monkey cells. Sequencing analyses revealed that these viruses encode capsid substitutions within the CypA-binding site (V86P/H87Q/I91V/M96I). 2005 The Journal of biological chemistry Abstract HIV V86P;H87Q;I91V;M96I 106;111;116;121 110;115;120;125 Capsid 55 61 16200350 Structural analysis of reverse transcriptase mutations at codon 215 explains the predominance of T215Y over T215F in HIV-1 variants selected under antiretroviral therapy. Mutation L210W further stabilized this aromatic pi-pi stacking interaction, increasing the affinity of the T215Y/L210W double mutant for ATP. 2005 Journal of biomedical science Abstract HIV L210W;L210W;T215Y 113;9;107 118;14;112 PI;PI 48;51 50;53 16200350 Structural analysis of reverse transcriptase mutations at codon 215 explains the predominance of T215Y over T215F in HIV-1 variants selected under antiretroviral therapy. Mutation T215F was preferentially associated with K70R (>71%), D67N (>73%) and K219Q/E/N (>76%), whereas T215Y was associated with M41L (>84%) and L210W (>58%). 2005 Journal of biomedical science Abstract HIV D67N;K219E;K219N;K219Q;K70R;L210W;M41L;T215F;T215Y 63;79;79;79;50;147;131;9;105 67;88;88;88;54;152;135;14;110 16200350 Structural analysis of reverse transcriptase mutations at codon 215 explains the predominance of T215Y over T215F in HIV-1 variants selected under antiretroviral therapy. Overall, this study provides a biochemical basis accounting for the evolutionary pathway of T215 mutations in HIV-1 RT, leading to the preferential selection of T215Y vs. 2005 Journal of biomedical science Abstract HIV T215Y 161 166 RT 116 118 16200350 Structural analysis of reverse transcriptase mutations at codon 215 explains the predominance of T215Y over T215F in HIV-1 variants selected under antiretroviral therapy. T215F. 2005 Journal of biomedical science Abstract HIV T215F 0 5 16200350 Structural analysis of reverse transcriptase mutations at codon 215 explains the predominance of T215Y over T215F in HIV-1 variants selected under antiretroviral therapy. We showed that mutation T215Y is predominant over T215F (respectively 38.8 vs. 2005 Journal of biomedical science Abstract HIV T215F;T215Y 50;24 55;29 16206068 Interruption of treatment with individual therapeutic drug classes in adults with multidrug-resistant HIV-1 infection. In contrast, all subjects who interrupted RTI treatment exhibited immediate increases in HIV RNA levels, and most exhibited a subsequent loss of the M184V mutation. 2005 The Journal of infectious diseases Abstract HIV M184V 149 154 RT 42 45 16206115 Resistance to nonnucleoside reverse-transcriptase inhibitors and prevalence of HIV type 1 non-B subtypes are increasing among persons with recent infection in Spain. There was a significant increase of K103N and of non-B subtypes over time. 2005 Clinical infectious diseases Abstract HIV K103N 36 41 16206233 Evasion of cytotoxic T lymphocytes is a functional constraint maintaining HIV-1 Nef expression. HIV-1 with functional Nef (wild type, WT) is compared to virus containing a Nef point mutation (M20A) that selectively ablates MHC-I down-regulation. 2005 European journal of immunology Abstract HIV M20A 96 100 Nef;Nef 22;76 25;79 16206233 Evasion of cytotoxic T lymphocytes is a functional constraint maintaining HIV-1 Nef expression. These viruses grow similarly in vitro in the absence of CTL, but the presence of Gag- or RT-specific CTL strongly favors WT overgrowth of M20A. 2005 European journal of immunology Abstract HIV M20A 138 142 Gag;RT 81;89 84;91 16206233 Evasion of cytotoxic T lymphocytes is a functional constraint maintaining HIV-1 Nef expression. WT-infected cells are relatively resistant to cytolysis and less suppressed for viral replication by Gag- and RT-specific CTL compared to M20A. 2005 European journal of immunology Abstract HIV M20A 138 142 Gag;RT 101;110 104;112 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Both N265D and Dbl RTs were resistant to most aptamers tested. 2005 AIDS research and therapy Abstract HIV N265D 5 10 RT 19 22 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. In order to address the wider applicability of such aptamers, HIV-1 RT variants containing the N255D, N265D or both (Dbl) were tested for the extent of their cross-resistance to other DNA/RNA aptamers as well as to other RT inhibitors. 2005 AIDS research and therapy Abstract HIV N255D;N265D 95;102 100;107 RT;RT 68;221 70;223 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. N255D mutant displayed mild resistance to two of the DNA aptamers, little change in sensitivity to three and hypersensitivity to one. 2005 AIDS research and therapy Abstract HIV N255D 0 5 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. This result was tempered by the observation that NRTI-resistance mutations such as K65R can confer resistance to some anti-RT aptamers. 2005 AIDS research and therapy Abstract HIV K65R 83 87 NRTI;RT 49;123 53;125 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. We previously reported mutants of HIV-1 RT with substitutions N255D or N265D that display resistance to the DNA aptamer RT1t49. 2005 AIDS research and therapy Abstract HIV N255D;N265D 62;71 67;76 RT 40 42 16218801 In vitro generation of HIV type 1 subtype C isolates resistant to enfuvirtide. All subtype C isolates showed evidence of genotypic changes in gp41 HR-1 following exposure to ENF that included G36S/E/D, I37T, V38M/A/L/E, N/S42D, N43K, L45R/M, and A50T/V. 2005 AIDS research and human retroviruses Abstract HIV A50T;A50V;G36D;G36E;G36S;I37T;L45M;L45R;N42D;N43K;S42D;V38A;V38E;V38L;V38M 167;167;113;113;113;123;155;155;141;149;141;129;129;129;129 173;173;121;121;121;127;161;161;147;153;147;139;139;139;139 gp41 63 67 16218957 Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. HIV-1 protease (PR) and two drug-resistant variants--PR with the V82A mutation (PR(V82A)) and PR with the I84V mutation (PR(I84V))--were studied using reduced peptide analogs of five natural cleavage sites (CA-p2, p2-NC, p6pol-PR, p1-p6 and NC-p1) to understand the structural and kinetic changes. 2005 The FEBS journal Abstract HIV I84V;I84V;V82A;V82A 106;124;65;83 110;128;69;87 PR;NC;NC;Gag;Capsid;PR;PR;PR;PR;PR;PR 6;217;241;234;207;16;53;80;94;121;227 14;219;243;236;209;18;55;82;96;123;229 16218957 Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. PR(I84V) showed reduced van der Waals interactions with inhibitor compared with PR, which was consistent with kinetic data. 2005 The FEBS journal Abstract HIV I84V 3 7 PR;PR 0;80 2;82 16218957 Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. PR(V82A) was able to compensate for the loss of interaction with inhibitor caused by mutation, in agreement with kinetic data, but substrate analogs have more flexibility than the drugs to accommodate the structural changes caused by mutation. 2005 The FEBS journal Abstract HIV V82A 3 7 PR 0 2 16218957 Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. The common drug-resistant mutations V82A and I84V alter residues forming the substrate-binding site. 2005 The FEBS journal Abstract HIV I84V;V82A 45;36 49;40 16218957 Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. The complexes of PR(V82A) showed smaller shifts of the main chain atoms of Ala82 relative to PR, but more movement of the peptide analog, compared to complexes with clinical inhibitors. 2005 The FEBS journal Abstract HIV V82A 20 24 PR;PR 17;93 19;95 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. Analysis of recombinant HIV-1s showed that HIV-1K103R/V179D was significantly resistant and HIV-1K103G was moderately resistant against EFV and NVP. 2006 Virology Abstract HIV K103R;V179D 48;54 53;59 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. K103N mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) confers high-level resistance against non-nucleoside RT inhibitors (NNRTIs) and it easily occurs partly because it arises by a single nucleotide substitution from wild-type K103. 2006 Virology Abstract HIV K103N 0 5 RT;NNRTI;RT;RT 62;157;85;142 83;163;87;144 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. R103G emerged by a single nucleotide substitution in one of three EFV cultures. 2006 Virology Abstract HIV R103G 0 5 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. R103N did not emerge in any of 7 NNRTI cultures. 2006 Virology Abstract HIV R103N 0 5 NNRTI 33 38 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. R103N does not seem to occur as easily as K103N because R103N requires two nucleotide substitutions. 2006 Virology Abstract HIV K103N;R103N;R103N 42;56;0 47;61;5 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. V179D emerged in all three EFV cultures and in two of four NVP cultures. 2006 Virology Abstract HIV V179D 0 5 16219331 Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. We found K103R polymorphic mutation in 3.3% of treatment-naive HIV-1-infected patients. 2006 Virology Abstract HIV K103R 9 14 HIV infections 63 77 16225378 Nelfinavir: a review of its use in the management of HIV infection. Resistance to nelfinavir may develop, but the most common mutation (D30N, appearing mainly in HIV-1 subtype B) does not confer resistance to other protease inhibitors, thereby conserving these agents for later use. 2005 Drugs Abstract HIV D30N 68 72 PR 147 155 16226779 The T12I mutation within the SP1 region of Gag restricts packaging of spliced viral RNA into human immunodeficiency virus type 1 with mutated RNA packaging signals and mutated nucleocapsid sequence. Interestingly, we have previously reported that the T12I mutation (named MP2) within SP1 of Gag prevented incorporation of spliced viral RNA into mutated viruses that lacked the stem-loop 1 (SL1) RNA element (also named dimerization initiation site, DIS), suggesting a role for the SP1 sequence in viral RNA packaging. 2006 Virology Abstract HIV T12I 52 56 SP1;SP1;Gag 85;282;92 88;285;95 16226779 The T12I mutation within the SP1 region of Gag restricts packaging of spliced viral RNA into human immunodeficiency virus type 1 with mutated RNA packaging signals and mutated nucleocapsid sequence. The results showed that MP2 was able to effectively restrict packaging of spliced viral RNA into viruses containing either NC mutations R10A and K11A or mutated 5' UTR sequence, such as DeltaGU3 that lacked the 112-GUCUGUUGUGUG-123 sequence of U5, D1 that was deleted of a 27 nt fragment immediately downstream of the primer binding site (PBS), Delta(306-325) that had the SL3 RNA element removed and MD2 that was missing the 328-GGAG-331 sequence. 2006 Virology Abstract HIV K11A;R10A 145;136 149;140 NC 123 125 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. For ABC, tenofovir, and d4T, despite having decreased excision, decreased binding or incorporation resulted in reduced susceptibilities to K65R. 2005 AIDS (London, England) Abstract HIV K65R 139 143 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. For ddI, ddC, 3TC, and FTC, decreased binding or incorporation by K65R appeared responsible for the decreased susceptibilities in cell culture. 2005 AIDS (London, England) Abstract HIV K65R 66 70 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. For K65R, the combination of these opposing mechanisms results in decreased susceptibility to most NRTI but increased susceptibility to ZDV. 2005 AIDS (London, England) Abstract HIV K65R 4 8 NRTI 99 103 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. However, K65R also showed decreased excision of all NRTI compared to wild-type, indicating greater stability once incorporated. 2005 AIDS (London, England) Abstract HIV K65R 9 13 NRTI 52 56 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. Ki/Km values were increased 2- to 13-fold for K65R compared to wild-type RT for all NRTI, indicating decreased binding or incorporation. 2005 AIDS (London, England) Abstract HIV K65R 46 50 NRTI;RT 84;73 88;75 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. METHODS: Susceptibilities of K65R mutant HIV-1 to NRTI were determined in cell culture. 2005 AIDS (London, England) Abstract HIV K65R 29 33 NRTI 50 54 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. OBJECTIVE: To determine the mechanisms of resistance of K65R mutant reverse transcriptase (RT) to the currently approved nucleoside and nucleotide RT inhibitors (NRTI). 2005 AIDS (London, England) Abstract HIV K65R 56 60 RT;NRTI;RT;RT 68;162;91;147 89;166;93;149 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. RESULTS: K65R HIV-1 had decreased susceptibility to most NRTI, but increased susceptibility to zidovudine (ZDV). 2005 AIDS (London, England) Abstract HIV K65R 9 13 NRTI 57 61 16227782 A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. The decreased binding or incorporation of ZDV by K65R appeared counteracted by decreased excision resulting in overall increased susceptibility to ZDV in cell culture. 2005 AIDS (London, England) Abstract HIV K65R 49 53 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. A Bayesian network model was used to map the resistance pathways in which M89I/V is involved for subtype G. 2005 AIDS (London, England) Abstract HIV M89I;M89V 74;74 80;80 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. CONCLUSIONS: The results of the present study show that M89I/V is associated with PI experience in subtypes C, F and G but not in subtype B. 2005 AIDS (London, England) Abstract HIV M89I;M89V 56;56 62;62 PI 82 84 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. However, when combined with L90M, a significantly reduced susceptibility to nelfinavir was observed (P < 0.05) in comparison with strains with L90M alone. 2005 AIDS (London, England) Abstract HIV L90M;L90M 28;143 32;147 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. M89I/V should be considered a secondary PI mutation with an important effect on nelfinavir susceptibility in the presence of L90M. 2005 AIDS (London, England) Abstract HIV L90M;M89I;M89V 125;0;0 129;6;6 PI 40 42 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. M89I/V was strongly associated with PI resistance mutations at codons 71, 74 and 90. 2005 AIDS (London, England) Abstract HIV M89I;M89V 0;0 6;6 PI 36 38 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. Phenotypically, M89I/V alone did not confer a reduced susceptibility to PIs. 2005 AIDS (London, England) Abstract HIV M89I;M89V 16;16 22;22 PI 72 75 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. RESULTS: The analysis showed that for the subtypes C, F and G in which the wild-type codon at 89 was M compared to L for subtype B, M89I/V was significantly more frequently observed in PI-treated patients displaying major resistance mutations to PIs than in drug-naive patients. 2005 AIDS (London, England) Abstract HIV M89I;M89V 132;132 138;138 PI;PI 185;246 187;249 16227787 Protease mutation M89I/V is linked to therapy failure in patients infected with the HIV-1 non-B subtypes C, F or G. The phenotypic effect of M89I/V for several PIs was also measured. 2005 AIDS (London, England) Abstract HIV M89I;M89V 25;25 31;31 PI 44 47 16227789 Detection of minor populations of drug-resistant HIV-1 in acute seroconverters. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction using allele-discriminating oligonucleotides for three key resistance mutations: L90M (protease), K103N and M184V (reverse transcriptase). 2005 AIDS (London, England) Abstract HIV K103N;L90M;M184V 209;192;219 214;196;224 RT;Pol;PR 226;85;198 247;95;206 16227789 Detection of minor populations of drug-resistant HIV-1 in acute seroconverters. The L90M mutation was found in one of 49 (2%), the K103N mutation in five of 49 (10.2%) and the M184V mutation in six of 49 (12.2%) patients, respectively. 2005 AIDS (London, England) Abstract HIV K103N;L90M;M184V 51;4;96 56;8;101 16227803 K65R and Y181C are less prevalent in HAART-experienced HIV-1 subtype A patients. We found that HAART-experienced patients infected with subtype A had a lower prevalence of K65R and Y181C than those with subtypes B or C, despite similar exposure to antiretroviral agents that select for these mutations. 2005 AIDS (London, England) Abstract HIV K65R;Y181C 91;100 95;105 16227805 A new insertion in the HIV-1 reverse transcriptase gene inducing major resistance to non-nucleoside reverse transcriptase inhibitors. The association of G190E and the 100-105 insertion displayed a high level of resistance to non-nucleoside reverse transcriptase inhibitors; the addition of the insertion to G190E may increase the activity of RT. 2005 AIDS (London, England) Abstract HIV G190E;G190E 19;173 24;178 NNRTI;RT 91;208 127;210 16227805 A new insertion in the HIV-1 reverse transcriptase gene inducing major resistance to non-nucleoside reverse transcriptase inhibitors. Virus carrying the insertion alone or in association with G190A was not infectious. 2005 AIDS (London, England) Abstract HIV G190A 58 63 16227805 A new insertion in the HIV-1 reverse transcriptase gene inducing major resistance to non-nucleoside reverse transcriptase inhibitors. We identified an HIV-1 isolate with a 3 base pairs insertion in the 100-105 region of the reverse transcriptase gene (RT) along with a G190E and a V75A mutation. 2005 AIDS (London, England) Abstract HIV G190E;V75A 135;147 140;151 RT;RT 90;118 111;120 16229872 Point mutations in the C-terminus of HIV-1 gp160 reduce apoptosis and calmodulin binding without affecting viral replication. Fas-mediated apoptosis levels positively correlated with the degree of calmodulin co-immunoprecipitation, with the lowest apoptosis levels occurring in cells infected with the A835W envelope mutation. 2006 Virology Abstract HIV A835W 176 181 Env 182 190 16229872 Point mutations in the C-terminus of HIV-1 gp160 reduce apoptosis and calmodulin binding without affecting viral replication. Four point mutations (A835W, A838W, A838I, and I842R) and the corresponding region of HIV-1 HXB2 were cloned into the HIV-1 proviral vector pNL4-3 with no significant effect on viral production or envelope expression, although co-immunoprecipitation of calmodulin and Env was decreased in three of these mutant viruses. 2006 Virology Abstract HIV A835W;A838I;A838W;I842R 22;36;29;47 27;41;34;52 Env;Env 197;268 205;271 16229872 Point mutations in the C-terminus of HIV-1 gp160 reduce apoptosis and calmodulin binding without affecting viral replication. The A835W mutation in the cytoplasmic domain of gp41 eliminated co-immunoprecipitation of Env with calmodulin in studies with stably transfected cells. 2006 Virology Abstract HIV A835W 4 9 gp41;Env 48;90 52;93 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Analysis of their effects on viral infection in a VSV-G pseudotyped RT/IN trans-complemented HIV-1 single cycle replication system revealed that all three C-terminal mutant viruses (KK215,9AA, KK240,4AE and RK263,4AA) exhibited more severe defect of induction of beta-Gal positive cells and luciferase activity than an IN class 1 mutant D64E in HeLa-CD4-CCR5-beta-Gal cells, and in dividing as well as non-dividing C8166 T cells, suggesting that some viral defects are occurring prior to viral integration. 2005 Retrovirology Abstract HIV D64E 337 341 IN;IN;RT 71;319;68 73;321;70 16245320 Binding energy analysis for wild-type and Y181C mutant HIV-1 RT/8-Cl TIBO complex structures: quantum chemical calculations based on the ONIOM method. Additional calculations involving the interaction energies between 8-Cl TIBO with individual residues surrounding the binding pocket were performed at MP2/6-31G(d,p) and B3LYP/6-31G(d,p) levels of theory to gain more insight into the energetic differences of wild-type and Y181C mutant type at the atomistic level. 2005 Proteins Abstract HIV Y181C 273 278 16245320 Binding energy analysis for wild-type and Y181C mutant HIV-1 RT/8-Cl TIBO complex structures: quantum chemical calculations based on the ONIOM method. The obtained results clearly indicate that the Y181C mutation reduces the binding affinity and stability of the inhibitor by approximately 8-9 kcal/mol as obtained from different combined MO:MO methods. 2005 Proteins Abstract HIV Y181C 47 52 16245320 Binding energy analysis for wild-type and Y181C mutant HIV-1 RT/8-Cl TIBO complex structures: quantum chemical calculations based on the ONIOM method. Two-layered and three-layered ONIOM calculations were performed to compare the binding energies of 8-Cl TIBO inhibitor when bound into the human immunodeficiency virus reverse transcriptase binding pocket and a Y181C variant. 2005 Proteins Abstract HIV Y181C 211 216 RT 168 189 16245645 In vitro activity of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI), against 215 HIV-1 isolates resistant to other NRTIs. M184V addition reduced SPD754 susceptibility by 1.8-fold in the presence or absence of TAMs. 2005 Antiviral chemistry & chemotherapy Abstract HIV M184V 0 5 16245645 In vitro activity of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI), against 215 HIV-1 isolates resistant to other NRTIs. SPD754 retains a substantial proportion of its antiviral activity against HIV-1 containing multiple TAMs, with or without the M184V mutation. 2005 Antiviral chemistry & chemotherapy Abstract HIV M184V 126 131 16247962 Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance. Alpha-boranophosphates suppress RT-mediated resistance when the catalytic rate of incorporation (kpol) of the analogue 5'-triphosphate is responsable for drug resistance, such as in the case of K65R mutant and ddNTPs, and Q151M toward AZTTP and ddNTPs. 2005 Nucleosides, nucleotides & nucleic acids Abstract HIV K65R;Q151M 194;222 198;227 RT 32 34 16247962 Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance. This suppression is also observed with BH3-d4T and BH3-3TC toward their clinically relevant mutants Q151M and M184V. 2005 Nucleosides, nucleotides & nucleic acids Abstract HIV M184V;Q151M 110;100 115;105 16249705 Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial. A major protease inhibitor resistance mutation (L90M) developed in 3 patients. 2005 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L90M 48 52 PR 8 16 16251284 Anti-human immunodeficiency virus type 1 activity of the nonnucleoside reverse transcriptase inhibitor GW678248 in combination with other antiretrovirals against clinical isolate viruses and in vitro selection for resistance. Resistant progeny viruses recovered after eight passages had amino acid substitutions V106I, E138K, and P236L in the reverse transcriptase-coding region in one passage series and amino acid substitutions K102E, V106A, and P236L in a second passage series. 2005 Antimicrobial agents and chemotherapy Abstract HIV E138K;K102E;P236L;P236L;V106A;V106I 93;204;104;222;211;86 98;209;109;227;216;91 RT 117 138 16251294 High potency of indolyl aryl sulfone nonnucleoside inhibitors towards drug-resistant human immunodeficiency virus type 1 reverse transcriptase mutants is due to selective targeting of different mechanistic forms of the enzyme. By comparing the activities of the different compounds against wild-type RT and the nonnucleoside reverse transcriptase inhibitor-resistant mutant Lys103Asn, it was possible to hypothesize, on the basis of their mechanism of action, a rationale for the design of drugs which could overcome the steric barrier imposed by the Lys103Asn mutation. 2005 Antimicrobial agents and chemotherapy Abstract HIV K103N;K103N 147;324 156;333 NNRTI;RT 84;73 119;75 16260913 Risk of selecting K65R in antiretroviral-naive HIV-infected individuals with chronic hepatitis B treated with adefovir. Using bulk population sequencing and a sensitive limiting dilution analysis, the selection of K65R or other resistance mutations did not occur in HIV, suggesting that adefovir can be confidently used as hepatitis B virus (HBV) therapy in HIV/HBV-co-infected patients who do not require antiretroviral therapy. 2005 AIDS (London, England) Abstract HIV K65R 94 98 16268822 Drug-resistance mutations in antiretroviral-naive patients with established HIV-1 infection in Mexico. For nonnucleoside inhibitors, mutations K103N/R (6%), Y181C (3%) and G190A (2%) were detected. 2005 HIV medicine Abstract HIV G190A;K103N;K103R;Y181C 69;40;40;54 74;47;47;59 16268822 Drug-resistance mutations in antiretroviral-naive patients with established HIV-1 infection in Mexico. For nucleoside inhibitors, mutations T215Y/C and F77L (3%) and D67N/S, T69N and M184V (2%), were detected. 2005 HIV medicine Abstract HIV D67N;D67S;F77L;M184V;T215C;T215Y;T69N 63;63;49;80;37;37;71 69;69;53;85;44;44;75 16270125 HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment. Failure with nelfinavir has been associated with two protease gene mutations, D30N and L90M. 2005 The Brazilian journal of infectious diseases Abstract HIV D30N;L90M 78;87 82;91 PR 53 61 16270125 HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment. In the tests for protease gene mutations, the D30N mutation was found in 57%, L90M in 18% and the wild-type virus in 25%. 2005 The Brazilian journal of infectious diseases Abstract HIV D30N;L90M 46;78 50;82 PR 17 25 16270125 HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment. Nucleosides associated with mutations (NAM) were observed in 80% of the tests; no INS69, complex 151, K65R and L74V mutations, which give multi-resistance to nucleoside analogue reverse transcriptase inhibitors to tenofovir and DDI, respectively, were observed. 2005 The Brazilian journal of infectious diseases Abstract HIV K65R;L74V 102;111 106;115 NRTI;IN 158;82 199;84 16270125 HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment. The D30N mutation does not result in cross-resistance with other protease inhibitors, and it decreases viral fitness. 2005 The Brazilian journal of infectious diseases Abstract HIV D30N 4 8 PR 65 73 16270125 HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment. These data are similar to published reports, showing that alternative therapies used after failure with nelfinavir may be more successful, as the D30N mutation does not cause cross-resistance to other protease inhibitors. 2005 The Brazilian journal of infectious diseases Abstract HIV D30N 146 150 PR 201 209 16275650 Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. 277, 5952-5961) and H219P substitutions in the viral CypA binding loop confer the greatest replication advantage to HIV-1. 2006 The Journal of biological chemistry Abstract HIV H219P 20 25 16275650 Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. Among the amino acid substitutions identified in Gag noncleavage sites in HIV-1 variants resistant to protease inhibitors, H219Q (Gatanaga, H., Suzuki, Y., Tsang, H., Yoshimura, K., Kavlick, M. 2006 The Journal of biological chemistry Abstract HIV H219Q 123 128 PR;Gag 102;49 110;52 16275650 Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. H219Q introduction also restored the otherwise compromised replication of HIV-1(P222A) in PBM, although the CypA content in HIV-1(H219Q/P222A) was comparable with that in HIV-1(P222A), suggesting that H219Q affected the conformation of the CypA-binding motif, rendering HIV-1 replicative in a low CypA environment. 2006 The Journal of biological chemistry Abstract HIV H219Q;H219Q;P222A;P222A;P222A;H219Q 130;201;136;80;177;0 135;206;141;85;182;5 16275650 Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. High intracellular CypA content in H9 and MT-2 cells, resulting in excessive CypA levels in virions, limited wild-type HIV-1 (HIV-1(WT)) replication and H219Q introduction into HIV-1 (HIV-1(H219Q)), reduced CypA incorporation of HIV-1, and potentiated viral replication. 2006 The Journal of biological chemistry Abstract HIV H219Q;H219Q 153;190 158;195 16275650 Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. Structural modeling analyses revealed that although hydrogen bonds are lost with H219Q and H219P substitutions, no significant distortion of the CypA binding loop of Gag occurred. 2006 The Journal of biological chemistry Abstract HIV H219P;H219Q 91;81 96;86 Gag 166 169 16275650 Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loop. The loop conformation of HIV-1(P222A) was found highly distorted, although H219Q introduction to HIV-1 restored the conformation of the loop close to that of HIV-1 (P222A). 2006 The Journal of biological chemistry Abstract HIV H219Q;P222A;P222A 75;165;31 80;170;36 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. Crystal structures of the mutants PR(L24I), PR(I50V) and PR(G73S) were determined in complexes with indinavir, or the p2/NC substrate analog at resolutions of 1.10-1.50 Angstrom. 2005 Journal of molecular biology Abstract HIV G73S;I50V;L24I 60;47;37 64;51;41 NC;PR;PR;PR 121;34;44;57 123;36;46;59 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. Inhibition constants (K(i)) of the antiviral drug indinavir for the reaction catalyzed by the mutant enzymes were about threefold and 50-fold higher for PR(L24I) and PR(I50V), respectively, relative to PR and PR(G73S). 2005 Journal of molecular biology Abstract HIV G73S;I50V;L24I 212;169;156 216;173;160 PR;PR;PR;PR 153;166;202;209 155;168;204;211 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. Mutation I50V alters a residue in the flexible flap that interacts with the inhibitor, L24I alters a residue adjacent to the catalytic Asp25, and G73S lies at the protein surface far from the inhibitor-binding site. 2005 Journal of molecular biology Abstract HIV G73S;I50V;L24I 146;9;87 150;13;91 Asp 135 138 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. PR(L24I) and PR(I50V), showed a 4% and 18% lower k(cat)/K(m), respectively, relative to PR. 2005 Journal of molecular biology Abstract HIV I50V;L24I 16;3 20;7 PR;PR;PR 0;13;88 2;15;90 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. Relative to PR, PR(I50V) had fewer interactions of Val50 with inhibitors, in agreement with the dramatically increased K(i). 2005 Journal of molecular biology Abstract HIV I50V 19 23 PR;PR 12;16 14;18 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. The crystal structures, dimer stabilities, and kinetics have been analyzed for wild-type human immunodeficiency virus type 1 (HIV-1) protease (PR) and resistant mutants PR(L24I), PR(I50V), and PR(G73S) to gain insight into the molecular basis of drug resistance. 2005 Journal of molecular biology Abstract HIV G73S;I50V;L24I 196;182;172 200;186;176 PR;PR;PR;PR;PR 133;143;169;179;193 141;145;171;181;195 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. The dimer dissociation constant (K(d)) was estimated to be approximately 20 nM for both PR(L24I) and PR(I50V), and below 5 nM for PR(G73S) and PR. 2005 Journal of molecular biology Abstract HIV G73S;I50V;L24I 133;104;91 137;108;95 PR;PR;PR;PR 88;101;130;143 90;103;132;145 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. The distal mutation G73S introduced new hydrogen bond interactions that can transmit changes to the substrate-binding site and alter catalytic activity. 2005 Journal of molecular biology Abstract HIV G73S 20 24 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. The mutated residues in PR(L24I) and PR(I50V) had reduced intersubunit contacts, consistent with the increased K(d) for dimer dissociation. 2005 Journal of molecular biology Abstract HIV I50V;L24I 40;27 44;31 PR;PR 24;37 26;39 16277992 Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. The relative k(cat)/K(m) of PR(G73S) varied from 14% to 400% when assayed using different substrates. 2005 Journal of molecular biology Abstract HIV G73S 31 35 PR 28 30 16279773 Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. Design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activity. The PBO derivatives specifically designed to target the highly conserved amino acid residues within the beta12-beta13 hairpin, namely primer grip, proved to be very potent against the most common mutant enzymes, including the highly resistant K103N mutant strain. 2005 Journal of medicinal chemistry Abstract HIV K103N 243 248 16282481 Effect of cell cycle arrest on the activity of nucleoside analogues against human immunodeficiency virus type 1. In drug-resistant reverse transcriptase mutants, the increase in AZT IC50 (relative to that in dividing cells) was most prominent with a Q151M mutant and was comparable to the wild type in other drug-resistant mutants. 2005 Journal of virology Abstract HIV Q151M 137 142 RT 18 39 16290277 Inhibition of drug-resistant HIV-1 by RNA interference. However, a combination of lamivudine and siRNA-M184V was very effective in inhibiting replication of both wild-type and variant M184V viruses in mixed infection experiments. 2006 Antiviral research Abstract HIV M184V;M184V 47;128 52;133 16290277 Inhibition of drug-resistant HIV-1 by RNA interference. To investigate specific inhibition of drug-resistant HIV-1 by RNA interference, we designed siRNA molecules that recognize codons 181-188 of the reverse transcriptase (RT) gene of wild-type HIV-1 and HIV-1 carrying the M184V mutation, which confers high-level resistance to the RT inhibitor lamivudine. 2006 Antiviral research Abstract HIV M184V 219 224 RT;RT;RT 145;168;278 166;170;280 16290277 Inhibition of drug-resistant HIV-1 by RNA interference. We have demonstrated that siRNA targeting either wild-type HIV-1 or M184V variants inhibits replication of the corresponding virus, but does not influence replication of virus with a mismatch in the targeted region. 2006 Antiviral research Abstract HIV M184V 68 73 16299731 Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors. A correlation was found between K20R and lamivudine resistance (P = 0.006) while T39A (P = 0.005), K43EQN (<0.001), E203KD (P = 0.010), and H208Y (P = < 0.001) seemed to be associated with a previous use of zidovudine and stavudine and with the development of thymidine analog resistance. 2006 Journal of medical virology Abstract HIV E203D;E203K;H208Y;K20R;K43E;K43N;K43Q;T39A 116;116;140;32;99;99;99;81 122;122;145;36;105;105;105;85 16299731 Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors. D218E showed a weak association to didanosine resistance (P = 0.013). 2006 Journal of medical virology Abstract HIV D218E 0 5 16299731 Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors. For H208Y, an association with use/resistance to abacavir (P = 0.004) was also noted. 2006 Journal of medical virology Abstract HIV H208Y 4 9 16299731 Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors. The mutations involving 10 of these positions were associated with a reduced susceptibility to antiretroviral drugs; K20R, T39A, K43EQN, E203KD, H208Y, and D218E were correlated with NRTI resistance while mutations K101EQP, H221Y, K223EQ, L228HR were associated to NNRTI resistance. 2006 Journal of medical virology Abstract HIV D218E;E203D;E203K;H208Y;H221Y;K101E;K101P;K101Q;K20R;K223E;K223Q;K43E;K43N;K43Q;L228H;L228R;T39A 156;137;137;145;224;215;215;215;117;231;231;129;129;129;239;239;123 161;143;143;150;229;222;222;222;121;237;237;135;135;135;245;245;127 NNRTI;NRTI 265;183 270;187 16302798 Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains. Lys103Asn, Tyr181Cys, and Tyr188Leu are some of the most common RT mutations that cause resistance to NNRTIs in the clinic. 2005 Journal of medicinal chemistry Abstract HIV K103N;Y181C;Y188L 0;11;26 9;20;35 NNRTI;RT 102;64 108;66 16302798 Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains. These compounds strongly inhibit wild-type HIV-1 RT and drug-resistant variants, including Tyr181Cys and Lys103Asn RT. 2005 Journal of medicinal chemistry Abstract HIV K103N;Y181C 105;91 114;100 RT;RT 49;115 51;117 16302798 Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains. These contacts appear to enhance the inhibitory activity of R221239 against the HIV-1 strains that carry the Val106Ala, Tyr188Leu, and Phe227Cys mutations. 2005 Journal of medicinal chemistry Abstract HIV F227C;V106A;Y188L 135;109;120 144;118;129 16305512 Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants. IAS derivatives bearing 2-hydroxyethylcarboxyamide or 2-hydroxyethylcarboxyhydrazide groups at position 2 of the indole nucleus were more active than L-737,126 against the K103N-Y181C double mutant. 2005 Current pharmaceutical design Abstract HIV K103N;Y181C 172;178 177;183 16305512 Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants. IAS having two halogen atoms at the indole showed potent inhibitory activity against the Y181C and the EFV(R) resistant mutant strains. 2005 Current pharmaceutical design Abstract HIV Y181C 89 94 16305512 Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants. The transformation of the chain terminus into amide or hydrazide, produced short peptides with high selectivity and potent activity against wt HIV-1, and the viral mutants Y181C, K103N-Y181C and EFV(R). 2005 Current pharmaceutical design Abstract HIV K103N;Y181C;Y181C 179;172;185 184;177;190 16305515 The antiviral activity, mechanism of action, clinical significance and resistance of abacavir in the treatment of pediatric AIDS. The M184V mutation appears to be the cornerstone of higher level resistance in regimens containing abacavir, imparting a 2-4 fold reduction in the susceptibility of HIV to abacavir. 2005 Current pharmaceutical design Abstract HIV M184V 4 9 16310238 HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice. Flow cytometry analysis showed that downregulation of murine CD4 was severely decreased or abrogated on Tg T cells expressing respectively Nef(RD35/36AA) and Nef(D174K). 2006 Virology Abstract HIV D174K 162 167 Nef;Nef 139;158 142;161 16310238 HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice. Histopathological assessment revealed the total absence of or decrease severity and frequency of organ AIDS-like diseases (lung, heart and kidney pathologies) in respectively Nef(RD35/36AA) and Nef(D174K) Tg mice, relative to those developing in Nef(Wt) Tg mice. 2006 Virology Abstract HIV D174K 198 203 Nef;Nef;Nef 175;194;246 178;197;249 16310238 HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice. Our data suggest that the RD35/36AA and D174K mutations affect other Nef functions, namely those involved in the development of lung and kidney diseases, in addition to their known role in CD4 downregulation. 2006 Virology Abstract HIV D174K 40 45 Nef 69 72 16310238 HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice. Similarly, the severe depletion of double-positive CD4+CD8+ and of single-positive CD4+CD8- thymocytes, usually observed with Nef(Wt), was not detected in Nef(RD35/36AA) and Nef(D174K) Tg mice. 2006 Virology Abstract HIV D174K 178 183 Nef;Nef;Nef 126;155;174 129;158;177 16310238 HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice. This was accompanied, as previously reported for Net(Wt) Tg mice, by the presence of an activated/memory-like phenotype (CD69+, CD25+, CD44+, CD45RB(Low), CD62(Low)) of CD4+ T cells expressing Nef(RD35/36AA) and to a lesser extent Nef(D174K). 2006 Virology Abstract HIV D174K 235 240 Nef;Nef 193;231 196;234 16310238 HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice. Two independent Nef mutants (RD35/36AA and D174K), known to abrogate CD4 downregulation, were tested in Tg mice. 2006 Virology Abstract HIV D174K 43 48 Nef 16 19 16312182 Short communication. Antiretroviral drug resistance among drug-naive HIV-1-infected individuals in Djibouti (Horn of Africa). A few strains displayed primary mutations (the non-nucleoside reverse transcriptase inhibitor [NNRTI]-associated mutations K101E, K103T, L100I and G190V; the PI-associated mutation N88D; and the NRTI-associated mutation K65R). 2005 Antiviral therapy Abstract HIV G190V;K101E;K103T;K65R;L100I;N88D 147;123;130;220;137;181 152;128;135;224;142;185 NNRTI;NNRTI;NRTI;PI 47;95;195;158 83;100;199;160 16312182 Short communication. Antiretroviral drug resistance among drug-naive HIV-1-infected individuals in Djibouti (Horn of Africa). The most frequent were secondary mutations associated with protease inhibitors (PIs): M36I, R41K and K20I/R. 2005 Antiviral therapy Abstract HIV K20I;K20R;M36I;R41K 101;101;86;92 107;107;90;96 PR;PI 59;80 67;83 16312183 Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. A decrease in susceptibility to all NRTIs was observed when Q151M was selected with V111I, a mutation of unknown impact on HIV-1 resistance. 2005 Antiviral therapy Abstract HIV Q151M;V111I 60;84 65;89 NRTI 36 41 16312183 Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. Four HIV-2 infected patients from the French ANRS HIV-2 cohort, with evidence of Q151M mutation in both plasma and available peripheral blood mononuclear cells (PBMCs) co-cultivated supernatants, were selected. 2005 Antiviral therapy Abstract HIV Q151M 81 86 16312183 Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. In HIV-2 infection, many studies have reported a high frequency of selection of the Q151M mutation, but its impact on phenotypic susceptibility of HIV-2 isolates remains unclear. 2005 Antiviral therapy Abstract HIV Q151M 84 89 HIV infections 3 18 16312183 Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. In HIV-2 isolates, the Q151M mutation alone impacts only the phenotypic susceptibility to stavudine and abacavir. 2005 Antiviral therapy Abstract HIV Q151M 23 28 16314108 Phosphoramidate and phosphate prodrugs of (-)-beta-D-(2R,4R)-dioxolane-thymine: synthesis, anti-HIV activity and stability studies. A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M184V mutants in PBM cells as well as for their cytotoxicity. 2006 Bioorganic & medicinal chemistry Abstract HIV M184V 178 183 16332074 Effect of a bound non-nucleoside RT inhibitor on the dynamics of wild-type and mutant HIV-1 reverse transcriptase. Molecular dynamics (MD), principal component analysis (PCA), and binding free energy simulations are employed to explore the dynamics of RT and its interaction with the bound NNRTI nevirapine, for both wild-type and mutant (V106A, Y181C, Y188C) RT. 2005 Journal of the American Chemical Society Abstract HIV V106A;Y181C;Y188C 224;231;238 229;236;243 NNRTI;RT;RT 175;137;245 180;139;247 16332398 Low prevalence of primary antiretroviral resistance mutations and predominance of HIV-1 clade C at polymerase gene in newly diagnosed individuals from south Brazil. Principal antiretroviral resistance mutations (ARM) were observed in 3% of the samples, two cases with K103N and one with M41L, L210W and T215Y, all in HIV-1 clade B infected men. 2006 Virus research Abstract HIV K103N;L210W;M41L;T215Y 103;128;122;138 108;133;126;143 16332431 Bleomycin has antiviral properties against drug-resistant HIV strains and sensitises virus to currently used antiviral agents. Three clinically relevant mutant HIV variants, including one containing the Q151M mutation conferring multinucleoside resistance, were equally as sensitive to BLM as the wild-type HXB2 strain. 2006 International journal of antimicrobial agents Abstract HIV Q151M 76 81 16338417 Wide-open 1.3 A structure of a multidrug-resistant HIV-1 protease as a drug target. A second structural change is triggered by the L90M mutation that results in reshaping the 23-32 segment. 2005 Structure (London, England Abstract HIV L90M 47 51 16338417 Wide-open 1.3 A structure of a multidrug-resistant HIV-1 protease as a drug target. Major differences between the wild-type and the variant include a structural change initiated by the M36V mutation and amplified by additional mutations in the flaps of the protease, resulting in a "wide-open" structure that represents an opening that is 8 A wider than the "open" structure of the wild-type protease. 2005 Structure (London, England Abstract HIV M36V 101 105 PR;PR 173;308 181;316 16355337 Response to antiretroviral therapy in HIV-infected patients attending a public, urban clinic in Kampala, Uganda. The most common mutation detected was K103N (found in 14 of 27 patients with virologic treatment failure). 2006 Clinical infectious diseases Abstract HIV K103N 38 43 16358744 [Protease and reverse transcriptase genetic polymorphism in HIV type 1 subtype A variants predominating in cis countries]. However, high frequencies of secondary mutations V77I in protease and A62V in RT (67% H 63%, respectively) linked to each other in most cases were observed. 2005 Molekuliarnaia biologiia Abstract HIV A62V;V77I 70;49 74;53 PR;RT 57;78 65;80 16358744 [Protease and reverse transcriptase genetic polymorphism in HIV type 1 subtype A variants predominating in cis countries]. In addition, three other variants were found: viruses not containing the substitutions V77I or A62V, and variants bearing only one of them. 2005 Molekuliarnaia biologiia Abstract HIV A62V;V77I 95;87 99;91 16358744 [Protease and reverse transcriptase genetic polymorphism in HIV type 1 subtype A variants predominating in cis countries]. The HIV-1 isolates bearing both substitutions (MutV77I/A62V) were also characterized by the presence of several synonymous mutations, suggesting common origin for these viruses. 2005 Molekuliarnaia biologiia Abstract HIV A62V;V77I 55;50 59;54 16369374 Substitutions in the reverse transcriptase and protease genes of HIV-1 subtype B in untreated individuals and patients treated with antiretroviral drugs. Among mutations that confer resistance to antiretroviral drugs, M184V was present in 76% of treated patients and K70R in 31% (A-->G transitions). 2005 MedGenMed Abstract HIV K70R;M184V 113;64 117;69 16369374 Substitutions in the reverse transcriptase and protease genes of HIV-1 subtype B in untreated individuals and patients treated with antiretroviral drugs. In PR, a L90M (T-->A substitution) was prevalent in 47% of protease inhibitor (PI)-treated patients. 2005 MedGenMed Abstract HIV L90M 9 13 PR;PI;PR 59;79;3 67;81;5 16369374 Substitutions in the reverse transcriptase and protease genes of HIV-1 subtype B in untreated individuals and patients treated with antiretroviral drugs. Other frequent mutations in RT included T215Y (C-->A and A-->T substitutions), which was prevalent in 31% of treated patients. 2005 MedGenMed Abstract HIV T215Y 40 45 RT 28 30 16372284 Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1. Double mutations N42T + N43D were observed in plasma RNA at 32 weeks and remained detectable up to 16 weeks after the withdrawal of the drug. 2006 Journal of medical virology Abstract HIV N42T;N43D 17;24 21;28 16372284 Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1. G36D mutation was associated with a value of T20-IC50 of 5 microg/ml. 2006 Journal of medical virology Abstract HIV G36D 0 4 16372284 Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1. In one non-responder patient, N43D substitution was detected at 12 weeks of treatment, in association with a value of T20-IC50 of 10 microg/ml (10-fold increase). 2006 Journal of medical virology Abstract HIV N43D 30 34 16372284 Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1. In three temporary responders, coinciding with viral load rebound, G36D, and N42T substitutions were observed at 12, 24, and 40 weeks. 2006 Journal of medical virology Abstract HIV G36D;N42T 67;77 71;81 16372284 Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1. Mutations V101G and E137K, not reported previously, were also observed in the HR2 region. 2006 Journal of medical virology Abstract HIV E137K;V101G 20;10 25;15 16372284 Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1. The S138A substitution in HR2 was observed in plasma RNA at 32 weeks, and both in plasma RNA and in PI DNA at 40 weeks, associated with an increase of the T20-IC50 to 25 microg/ml (25-fold increase). 2006 Journal of medical virology Abstract HIV S138A 4 9 PI 100 102 16377678 Preliminary mapping of a putative inhibitor-binding pocket for human immunodeficiency virus type 1 integrase inhibitors. All mutant IN proteins demonstrated decreased susceptibility to l-CA, while all mutant proteins except E92K and K156R demonstrated resistance to L-731,988. 2006 Antimicrobial agents and chemotherapy Abstract HIV E92K;K156R 103;112 107;117 IN;Capsid 11;66 13;68 16377678 Preliminary mapping of a putative inhibitor-binding pocket for human immunodeficiency virus type 1 integrase inhibitors. Most proteins were also attenuated for disintegration; the IN that contained K156R and C65S-K156N, however, displayed disintegration activity similar to that of IN from HIV(NL4-3). 2006 Antimicrobial agents and chemotherapy Abstract HIV C65S;K156N;K156R 87;92;77 91;97;82 IN;IN 59;161 61;163 16377678 Preliminary mapping of a putative inhibitor-binding pocket for human immunodeficiency virus type 1 integrase inhibitors. Specifically, the single mutations E92K, Q148A, K156A, K156R, G140S, and G149S, as well as the double mutations C65S-K156N and H67D-G140A were evaluated for their effects on enzymatic activity and inhibitor susceptibility. 2006 Antimicrobial agents and chemotherapy Abstract HIV C65S;E92K;G140A;G140S;G149S;H67D;K156A;K156N;K156R;Q148A 112;35;132;62;73;127;48;117;55;41 116;39;137;67;78;131;53;122;60;46 16377709 The K101P and K103R/V179D mutations in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nonnucleoside reverse transcriptase inhibitors. Among samples with no known NNRTI mutations, the most resistant samples contained K101P (n = 35) or a combination of K103R and V179D (n = 41). 2006 Antimicrobial agents and chemotherapy Abstract HIV K101P;K103R;V179D 82;117;127 87;122;132 NNRTI 28 33 16386016 In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients. In conclusion, following NNRTI discontinuation, HIV variants carrying the K103N mutation are not overgrown for long by wild-type quasispecies at this position in the majority of patients, although treatment interruption favours their disappearance. 2005 The new microbiologica Abstract HIV K103N 74 79 NNRTI 25 30 16386016 In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients. No significant trend was found in relation to the disappearance of K103N variants in either group, but patients tested while receiving antiretrovirals had a significantly higher probability of retaining the K103N mutation over 24 months than those tested during treatment interruption (P = 0.007). 2005 The new microbiologica Abstract HIV K103N;K103N 67;207 72;212 16386016 In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients. This suggests that the K103N mutation per se has little impact on viral fitness in vivo. 2005 The new microbiologica Abstract HIV K103N 23 28 16386016 In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients. To investigate the dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTIs), we selected the Human Immunodeficiency Virus (HIV)-infected patients with the mutation at the time or after the failure of an NNRTI-containing regimen from an observational database. 2005 The new microbiologica Abstract HIV K103N 35 40 NNRTI;NNRTI;NNRTI 78;127;262 114;133;267 16386114 Full sequence of HIV type 1 Korean subtype B in an AIDS case with atypical seroconversion: TAAAA at TATA box. The major differences in the level of the HIV-1 gene between the seronegative and seropositive states were changes at the glycosylation site (NXT) next to the inserted proline and many resistance mutations including M184V to antiretroviral drugs occurred. 2005 AIDS research and human retroviruses Abstract HIV M184V 216 221 16386116 Characterization of mutations in HIV type 1 isolates from 144 Cambodian recently infected patients and pregnant women naive to antiretroviral drugs. According to the ANRS September 2004 list, polymorphism substitutions (>50% versus the subtype B consensus) of CRF01_AE at drug resistance positions were observed only in protease: I13V (81%), E35D (87%), M36I (100%), R41K (96%), and H69K (100%). 2005 AIDS research and human retroviruses Abstract HIV E35D;H69K;I13V;M36I;R41K 193;234;181;205;218 197;238;185;209;222 PR 171 179 16386116 Characterization of mutations in HIV type 1 isolates from 144 Cambodian recently infected patients and pregnant women naive to antiretroviral drugs. Five other strains carried drug resistance mutations to RTIs: K70R (one strain), V75M (three strains), and K101E (one strain). 2005 AIDS research and human retroviruses Abstract HIV K101E;K70R;V75M 107;62;81 112;66;85 RT 56 60 16386116 Characterization of mutations in HIV type 1 isolates from 144 Cambodian recently infected patients and pregnant women naive to antiretroviral drugs. Two strains bore one major resistance mutation to PIs: M46I and N88D. 2005 AIDS research and human retroviruses Abstract HIV M46I;N88D 55;64 59;68 PI 50 53 16386461 Clinical utility of genotyping resistance test on determining the mutation patterns in HIV-1 CRF01_AE and subtype B patients receiving antiretroviral therapy in Hong Kong. However, the frequencies of L74V/I and K103N in the reverse transcriptase region were different between CRF01_AE and subtype B viruses. 2006 Journal of clinical virology Abstract HIV K103N;L74I;L74V 39;28;28 44;34;34 RT 52 73 16403521 Structural insights into the mechanisms of drug resistance in HIV-1 protease NL4-3. We have also obtained the crystal structures of three mutant forms of NL4-3 protease containing one (V82A), three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point mutations in complex with TL-3. 2006 Journal of molecular biology Abstract HIV F53L;F53L;L24I;L63P;M46I;M46I;V77I;V82A;V82A;V82A 127;154;166;172;121;148;160;101;115;142 131;158;170;176;125;152;164;105;119;146 PR 76 84 16404607 Prevalence and pattern of drug resistance mutations among antiretroviral-treated HIV-1 patients with suboptimal virological response in Malaysia. A patient with Q151M mutation complex was also detected. 2006 Medical microbiology and immunology Abstract HIV Q151M 15 20 16404607 Prevalence and pattern of drug resistance mutations among antiretroviral-treated HIV-1 patients with suboptimal virological response in Malaysia. In the RT gene, the frequency of mutations associated with NRTIs and NNRTIs resistance was 52.8 and 63.9%, respectively, with M184V and K103N mutations being selected most frequently by these drugs. 2006 Medical microbiology and immunology Abstract HIV K103N;M184V 136;126 141;131 NNRTI;NRTI;RT 69;59;7 75;64;9 16407193 Activation of p21-activated kinase 2 and its association with Nef are conserved in murine cells but are not sufficient to induce an AIDS-like disease in CD4C/HIV transgenic mice. Among other Tg mice expressing Nef mutants having conserved the Nef-PAK2 association (RD35AA, D174K, P147A/P150A, Delta8-17, and Delta25-65), only Tg mice expressing Nef(Delta8-17) develop kidney and lung diseases, but all showed partial CD4(+) T cell depletion despite some being defective for CD4 down-regulation (RD35AA and D174K). 2006 The Journal of biological chemistry Abstract HIV D174K;D174K;P147A;P150A 94;327;101;107 99;332;106;112 Nef;Nef;Nef 31;64;166 34;67;169 Kidney and lung diseases 189 213 16407193 Activation of p21-activated kinase 2 and its association with Nef are conserved in murine cells but are not sufficient to induce an AIDS-like disease in CD4C/HIV transgenic mice. Among these, only Tg mice expressing Nef(P69A) and Nef(G2A) showed some depletion of CD4(+) T cells, although a down-regulation of the CD4 surface protein was documented in all these Tg lines, except those expressing Nef(Delta56-66). 2006 The Journal of biological chemistry Abstract HIV G2A;P69A 55;41 58;45 Nef;Nef;Nef 37;51;217 40;54;220 16407193 Activation of p21-activated kinase 2 and its association with Nef are conserved in murine cells but are not sufficient to induce an AIDS-like disease in CD4C/HIV transgenic mice. CD4C/HIV Tg mice expressing Nef alleles defective in Nef-PAK2 association (P69A, P72A/P75A, R105A/R106A, Delta56-66, or G2A (myristoylation site)) failed to develop disease of the non-lymphoid organs (kidneys and lungs). 2006 The Journal of biological chemistry Abstract HIV G2A;P69A;P72A;P75A;R105A;R106A 120;75;81;86;92;98 123;79;85;90;97;103 Nef;Nef 28;53 31;56 16417938 Prevalence of antiretroviral drug resistance mutations and HIV-1 non-B subtypes in newly diagnosed drug-naive patients in Slovenia, 2000-2004. Namely, three out of 77 patients had mutations associated with resistance to NRTIs: one patient carried M184V in association with A62V, while a revertant mutation T215D was found in two patients. 2006 Virus research Abstract HIV A62V;M184V;T215D 130;104;163 134;109;168 NRTI 77 82 16420058 Structure-activity relationship studies of novel benzophenones leading to the discovery of a potent, next generation HIV nonnucleoside reverse transcriptase inhibitor. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC(50) values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. 2006 Journal of medicinal chemistry Abstract HIV K103N;Y181C 147;233 152;238 16421366 Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. In none of the patients did the K65R mutation develop. 2006 The New England journal of medicine Abstract HIV K65R 32 36 16423828 Structural determinants of slippage-mediated mutations by human immunodeficiency virus type 1 reverse transcriptase. The crystal structure of HIV-1 RT reveals a salt bridge between Glu(89) and Lys(154), which may facilitate -1 frameshifting; this concept is supported by the observed reduction in -1 frameshifting for K154A and K154R mutants. 2006 The Journal of biological chemistry Abstract HIV K154A;K154R 201;211 206;216 RT 31 33 16426053 A multivariate analysis of HIV-1 protease inhibitors and resistance induced by mutation. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. 2006 Journal of chemical information and modeling Abstract HIV I84V 50 54 16426053 A multivariate analysis of HIV-1 protease inhibitors and resistance induced by mutation. This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. 2006 Journal of chemical information and modeling Abstract HIV I84V;V82A;V82F 268;252;258 272;256;262 PR;PR;PI 159;286;180 167;294;183 16430939 Co-evolution of nelfinavir-resistant HIV-1 protease and the p1-p6 substrate. Using the chi2 test, we show a positive correlation between the nelfinavir-resistant D30N/N88D protease mutations and mutations at the p1-p6 cleavage site as compared to the other cleavage sites. 2006 Virology Abstract HIV D30N;N88D 85;90 89;94 PR;Gag 95;138 103;140 16432030 Influence of naturally occurring insertions in the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and mutation frequencies in vitro. M41L and T215Y) or an A62V mutation and confers resistance to multiple nucleoside analogue inhibitors. 2006 The Journal of general virology Abstract HIV A62V;T215Y;M41L 22;9;0 26;14;4 16432030 Influence of naturally occurring insertions in the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and mutation frequencies in vitro. Some multi-nucleoside analogue-resistant variants contain a T69S substitution along with dipeptide insertions between residues 69 and 70. 2006 The Journal of general virology Abstract HIV T69S 60 64 16432030 Influence of naturally occurring insertions in the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and mutation frequencies in vitro. T69S-AG, T69S-SG and T69S-SS alone, in combination with 3'-azido-2',3'-deoxythymidine-resistance mutations M41L, L210W, R211K, L214F, T215Y (LAG(AZ) and LSG(AZ)) or with an alternate set where A62V substitution replaces M41L (VAG(AZ), VSG(AZ) and VSS(AZ)). 2006 The Journal of general virology Abstract HIV A62V;L210W;L214F;M41L;M41L;R211K;T215Y;T69S;T69S;T69S 193;113;127;107;220;120;134;9;21;0 197;118;132;111;224;125;139;13;25;4 16436719 In vitro antiretroviral activity and in vitro toxicity profile of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus infection. Insertions at amino acid position 69 and Q151M mutations (with or without M184V) reduced SPD754 susceptibility 5.2-fold and 14- to 16-fold, respectively (these changes gave values comparable to or less than the corresponding values for zidovudine, lamivudine, abacavir, and didanosine). 2006 Antimicrobial agents and chemotherapy Abstract HIV M184V;Q151M 74;41 79;46 16436719 In vitro antiretroviral activity and in vitro toxicity profile of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus infection. SPD754 susceptibility was reduced 1.2- to 2.2-fold against isolates resistant to zidovudine (M41L, T215Y/F, plus a median of three additional nucleoside analogue mutations [NAMs]) and/or lamivudine (M184V) and was reduced 1.3- to 2.8-fold against isolates resistant to abacavir (L74V, Y115F, and M184V plus one other NAM) or stavudine (V75T/M, M41L, T215F/Y, and four other NAMs). 2006 Antimicrobial agents and chemotherapy Abstract HIV L74V;M184V;M184V;M41L;M41L;T215F;T215F;T215Y;T215Y;V75M;V75T;Y115F 279;199;296;93;344;99;350;99;350;336;336;285 283;204;301;97;348;106;357;106;357;342;342;290 16438641 Genotypic and phenotypic analyses of human immunodeficiency virus type 1 in antiretroviral drug-naive Nigerian patients. Within the protease region, all 18 isolates had mutations/polymorphic substitutions at six locations compared to the HIV-1 NL4-3 reference sequence, two of which have been associated with resistance to protease inhibitors (K20I and M36I). 2006 AIDS research and human retroviruses Abstract HIV K20I;M36I 223;232 228;236 PR;PR 11;202 19;210 16438641 Genotypic and phenotypic analyses of human immunodeficiency virus type 1 in antiretroviral drug-naive Nigerian patients. Within the reverse transcriptase (RT) region, all 18 isolates showed an E291D mutation/polymorphic substitution. 2006 AIDS research and human retroviruses Abstract HIV E291D 72 77 RT;RT 11;34 32;36 16438647 Selection and characterization of a replication-competent human immunodeficiency virus type 1 variant encoding C-terminally truncated env. In comparison to pNL-Tr752 and pNL-Wt, pNL-Tr752(N750K) glycoprotein exhibited increased fusion induction and 2- to 3-fold increased incorporation into particles, properties that may contribute to the observed replication competence. 2006 AIDS research and human retroviruses Abstract HIV N750K 49 54 16438647 Selection and characterization of a replication-competent human immunodeficiency virus type 1 variant encoding C-terminally truncated env. We have analyzed the properties of replication-competent pNL-Tr752(N750K) in comparison to its defective counterpart pNL-Tr752 and to wild-type virus in H9 cells. 2006 AIDS research and human retroviruses Abstract HIV N750K 67 72 16438647 Selection and characterization of a replication-competent human immunodeficiency virus type 1 variant encoding C-terminally truncated env. We report here that a single amino acid change (N750K) in the context of the mutant virus pNL-Tr752 lacking 104 C-terminal Env amino acids gives rise to a virus variant pNL-Tr752(N750K), which can now replicate in nonpermissive H9 cells and, albeit to a lower extent, in PBMCs. 2006 AIDS research and human retroviruses Abstract HIV N750K;N750K 48;179 53;184 Env 123 126 16439544 Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. The Q168A mutation in integrase has been shown to interfere with the interaction with LEDGF/p75 without reducing the enzymatic activity. 2006 Journal of virology Abstract HIV Q168A 4 9 IN 22 31 16439544 Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. Transduction by HIV-1-derived lentivectors carrying the Q168A IN mutant was severely hampered, pointing again to a requirement for LEDGF/p75. 2006 Journal of virology Abstract HIV Q168A 56 61 IN 62 64 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. Finally, we studied the incorporation of these deoxycytidine analogues into a HIV-1 genomic DNA/DNA primer/template by K65R HIV-1 RT to address certain concerns associated with DNA sequence specificity. 2006 Nucleosides, nucleotides & nucleic acids Abstract HIV K65R 119 123 RT 130 132 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. In this study, we measured the antiviral activity of FTC and 3TC against HIV-1 containing K65R, Q151M, and K65R/Q151M mutations. 2006 Nucleosides, nucleotides & nucleic acids Abstract HIV K65R;K65R;Q151M;Q151M 90;107;112;96 94;111;117;101 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. Overall, this study demonstrated that K65R and K65R/Q151M related drug resistance to FTC and 3TC was mainly due to a significant decrease in the rate of incorporation. 2006 Nucleosides, nucleotides & nucleic acids Abstract HIV K65R;K65R;Q151M 38;47;52 42;51;57 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. The double mutation K65R/Q151M has been shown to be more resistant to many NRTIs than either of the single mutations alone. 2006 Nucleosides, nucleotides & nucleic acids Abstract HIV K65R;Q151M 20;25 24;30 NRTI 75 80 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. The K65R mutation in the HIV reverse transcriptase (RT) confers reduced susceptibility to 3TC, ddC, ddI, abacavir, and tenofovir in vitro. 2006 Nucleosides, nucleotides & nucleic acids Abstract HIV K65R 4 8 RT;RT 29;52 50;54 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. The Q151M mutation confers reduced susceptibility to many of the approved anti-HIV nucleoside analogues with the exception of 3TC and tenofovir. 2006 Nucleosides, nucleotides & nucleic acids Abstract HIV Q151M 4 9 16440988 Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. The Q151M mutation remained sensitive to both FTC and 3TC in both cell culture and enzymatic assays. 2006 Nucleosides, nucleotides & nucleic acids Abstract HIV Q151M 4 9 16452063 Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study. 14 pts with K65R and M184V/I were given a rescue therapy with a successful outcome (< 50 copies/mL; median follow-up 48 weeks). 2005 HIV clinical trials Abstract HIV K65R;M184I;M184V 12;21;21 16;28;28 16452063 Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study. 76% of pts developed K65R and M184V/I mutations by W24, and 19% developed M184V/I alone. 2005 HIV clinical trials Abstract HIV K65R;M184I;M184I;M184V;M184V 21;30;74;30;74 25;37;81;37;81 16452063 Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study. CONCLUSION: Convergent genetic pathway to resistance, in conjunction with lower antiretroviral potency, may explain the high rate of selection K65R and M184V mutations. 2005 HIV clinical trials Abstract HIV K65R;M184V 143;152 147;157 16470121 Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. Comparing groups of patients with progressive disease (Pr + MEP) and groups with non-progressive disease (LTNP + STP) the probability of harbouring the R77Q mutation was significantly higher in non-progressors (odds ratio, 5.16; P = 0.001). 2006 AIDS (London, England) Abstract HIV R77Q 152 156 PR 55 57 16470121 Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. CONCLUSIONS: Our results support the hypothesis of the association of R77Q mutation in the Vpr gene with delayed progression of HIV-1 disease. 2006 AIDS (London, England) Abstract HIV R77Q 70 74 Vpr 91 94 16470121 Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. R77Q does not seem to be linked to a particular viral strain but might be associated to immunologic selection. 2006 AIDS (London, England) Abstract HIV R77Q 0 4 16470121 Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. RESULTS: A significantly higher prevalence of the R77Q mutation was evidenced both in LTNP (86.7%) and STP (73.9%) in comparison with Pr (42.1%) and MEP (42.1%), (P = 0.007). 2006 AIDS (London, England) Abstract HIV R77Q 50 54 PR 134 136 16470121 Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. The R77Q mutation might reduce CD4+ T-cell depletion possibly affecting T-cell survival in vivo by altering the pro-apoptotic activity of Vpr. 2006 AIDS (London, England) Abstract HIV R77Q 4 8 Vpr 138 141 16472877 In vitro selection of mutations in human immunodeficiency virus type 1 reverse transcriptase that confer resistance to capravirine, a novel nonnucleoside reverse transcriptase inhibitor. Interestingly, HIV-1 variants constructed to contain the T215Y zidovudine (AZT)-resistance associated substitution with CPV-resistance associated substitutions V106A, Y181C, F227C, F227L, L234I or V106A/F227L demonstrated 2.4-5.4-fold increased susceptibility to CPV. 2006 Antiviral research Abstract HIV F227C;F227L;F227L;L234I;T215Y;V106A;V106A;Y181C 174;181;203;188;57;160;197;167 179;186;208;193;62;165;202;172 16472877 In vitro selection of mutations in human immunodeficiency virus type 1 reverse transcriptase that confer resistance to capravirine, a novel nonnucleoside reverse transcriptase inhibitor. Results also demonstrate that the CPV-resistance associated substitutions Y181C, F227C, F227L and L234I reverse the phenotypic resistance to AZT conferred by the T215Y substitution. 2006 Antiviral research Abstract HIV F227C;F227L;L234I;T215Y;Y181C 81;88;98;162;74 86;93;103;167;79 16472877 In vitro selection of mutations in human immunodeficiency virus type 1 reverse transcriptase that confer resistance to capravirine, a novel nonnucleoside reverse transcriptase inhibitor. Results demonstrate that HIV-1 variants selected at increasing CPV concentrations contained multiple substitutions in diverse patterns including L100I, Y181C, G190E and/or L234I in various combinations with K101R/E, K103T, V106A/I, V108I, E138K, T139K, A158T, V179D/I/G, Y188D, V189I, G190A, F227C, W229R, L234F, M230I/L and P236H/T. 2006 Antiviral research Abstract HIV A158T;E138K;F227C;G190A;G190E;K101E;K101R;K103T;L100I;L234F;L234I;M230I;M230L;P236H;P236T;T139K;V106A;V106I;V108I;V179D;V179G;V179I;V189I;W229R;Y181C;Y188D 253;239;292;285;159;207;207;216;145;306;172;313;313;325;325;246;223;223;232;260;260;260;278;299;152;271 258;244;297;290;164;214;214;221;150;311;177;320;320;332;332;251;230;230;237;269;269;269;283;304;157;276 16474147 A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. Here we show that substitution of Asp for Leu at position 49 (L49D) in MA results in a specific reduction in particle-associated gp120 without affecting the levels of gp41. 2006 Journal of virology Abstract HIV L49D;L49D 62;34 66;60 gp120;gp41;Asp;Matrix 129;167;34;71 134;171;37;73 16474147 A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. Studies with HIV-1 particles containing decreased levels of envelope proteins suggested that the L49D mutation also inhibits a postentry step in infection. 2006 Journal of virology Abstract HIV L49D 97 101 Env 60 68 16474147 A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. The impaired fusion and infectivity of L49D mutant particles were also complemented by a single point mutation in the gp41 CT that disrupted the tyrosine-containing endocytic motif. 2006 Journal of virology Abstract HIV L49D 39 43 gp41 118 122 16474147 A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. Truncation of gp41 also resulted in equivalent levels of gp120 on particles with and without the MA mutation and enhanced the replication of the L49D mutant virus in T cells. 2006 Journal of virology Abstract HIV L49D 145 149 gp120;gp41;Matrix 57;14;97 62;18;99 16474147 A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. Truncation of the gp41 tail, or pseudotyping by vesicular stomatitis virus glycoprotein, restored both the fusion and infectivity of L49D mutant virions to wild-type levels. 2006 Journal of virology Abstract HIV L49D 133 137 gp41 18 22 16478392 Short communication: low prevalence of genotypic drug resistance mutations among antiretroviral-naive HIV type 1 patients in Malaysia. Amino acid substitutions I13V, E35D, and M36I were associated with CRF01_AE while L63P, V77I, and I93L were associated with subtype B. 2006 AIDS research and human retroviruses Abstract HIV E35D;I13V;I93L;L63P;M36I;V77I 31;25;98;82;41;88 35;29;102;86;45;92 16478392 Short communication: low prevalence of genotypic drug resistance mutations among antiretroviral-naive HIV type 1 patients in Malaysia. The prevalence of patients with at least one major mutation conferring drug resistance was 1%, with only one patient having a Y181C amino acid substitution in the RT gene that confers high-level resistance to nevirapine and delavirdine. 2006 AIDS research and human retroviruses Abstract HIV Y181C 126 131 RT 163 165 16478404 HIV type 1 pol gene diversity and antiretroviral drug resistance mutations in the Democratic Republic of Congo (DRC). Although at the time of our study ARV use was not yet widespread in DRC, three strains were identified with one major mutation associated with drug resistance: L90M and M46L in protease and K103N in RT. 2006 AIDS research and human retroviruses Abstract HIV K103N;L90M;M46L 190;160;169 195;164;173 PR;RT 177;199 185;201 16480273 Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. In PR(D30N), the inhibitor has a water-mediated interaction with the side chain of Asn30 rather than the direct interaction observed in PR, which is consistent with the relative inhibition. 2006 Journal of medicinal chemistry Abstract HIV D30N 6 10 PR;PR 3;136 5;138 16480273 Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. Similarly, in PR(I50V) the inhibitor loses favorable hydrophobic interactions with the side chain of Val50. 2006 Journal of medicinal chemistry Abstract HIV I50V 17 21 PR 14 16 16480273 Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. The inhibition constants (K(i)) of TMC-114 for mutants PR(D30N), PR(I50V), and PR(L90M) were 30-, 9-, and 0.14-fold, respectively, relative to wild-type PR. 2006 Journal of medicinal chemistry Abstract HIV D30N;I50V;L90M 58;68;82 62;72;86 PR;PR;PR;PR 55;65;79;153 57;67;81;155 16480273 Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. The potent new antiviral inhibitor TMC-114 (UIC-94017) of HIV-1 protease (PR) has been studied with three PR variants containing single mutations D30N, I50V, and L90M, which provide resistance to the major clinical inhibitors. 2006 Journal of medicinal chemistry Abstract HIV D30N;I50V;L90M 146;152;162 150;156;166 PR;PR;PR 64;74;106 72;76;108 16480273 Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. TMC-114 has additional van der Waals contacts in PR(L90M) structure compared to the PR structure, leading to a tighter binding of the inhibitor. 2006 Journal of medicinal chemistry Abstract HIV L90M 52 56 PR;PR 49;84 51;86 16492163 Drug resistance of HIV-1 protease against JE-2147: I47V mutation investigated by molecular dynamics simulation. In this work, the molecular details of the effect of I47V mutation is investigated using molecular dynamics simulation. 2006 Chemical biology & drug design Abstract HIV I47V 53 57 16492163 Drug resistance of HIV-1 protease against JE-2147: I47V mutation investigated by molecular dynamics simulation. Noteworthy, it is less susceptible to several common mutations, but it is still susceptible to a few mutations, including I47V which appears to be specific for JE-2147. 2006 Chemical biology & drug design Abstract HIV I47V 122 126 16495277 In vitro development of resistance to human immunodeficiency virus protease inhibitor GW640385. The A28S substitution substantially reduced replication capacity. 2006 Antimicrobial agents and chemotherapy Abstract HIV A28S 4 8 16495277 In vitro development of resistance to human immunodeficiency virus protease inhibitor GW640385. Variants characterized included one with <4-fold resistance and amino acid substitutions Q58E/A71V (protease) and P452K (Gag) and one with >50-fold resistance and amino acid substitutions L10F/G16E/E21K/A28S/M46I/F53L/A71V (protease) and L449F/P453T (Gag). 2006 Antimicrobial agents and chemotherapy Abstract HIV A28S;A71V;E21K;F53L;G16E;L10F;M46I;A71V;L449F;P452K;P453T;Q58E 203;218;198;213;193;188;208;94;238;114;244;89 207;222;202;217;197;192;212;98;243;119;249;93 PR;PR;Gag;Gag 100;224;121;251 108;232;124;254 16497663 Modification of human immunodeficiency virus type 1 reverse transcriptase to target cells with elevated cellular dNTP concentrations. Although the wild type HIV-1 vector transduced both HLFs and tumor cells, the Q151N vector failed to transduce HLFs and keratinocytes but efficiently transduced tumor cells. 2006 The Journal of biological chemistry Abstract HIV Q151N 78 83 16497663 Modification of human immunodeficiency virus type 1 reverse transcriptase to target cells with elevated cellular dNTP concentrations. Indeed, the modified HIV-1 vector harboring the Q151N mutant RT preferentially transduced tumor cells containing higher cellular dNTP concentrations than primary cells (e.g. 2006 The Journal of biological chemistry Abstract HIV Q151N 48 53 RT 61 63 16497663 Modification of human immunodeficiency virus type 1 reverse transcriptase to target cells with elevated cellular dNTP concentrations. We also observed that the Q151N vector expressing herpes simplex virus-thymidine kinase renders tumor cells sensitive to gancyclovir. 2006 The Journal of biological chemistry Abstract HIV Q151N 26 31 16497663 Modification of human immunodeficiency virus type 1 reverse transcriptase to target cells with elevated cellular dNTP concentrations. We employed an HIV-1 reverse transcriptase (RT) mutant (Q151N), which is catalytically active only at high dNTP concentrations because of its reduced dNTP binding affinity. 2006 The Journal of biological chemistry Abstract HIV Q151N 56 61 RT;RT 21;44 42;46 16503141 Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant. A series of aryltetrazolylacetanilides was synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors on wild-type virus and on the clinically relevant K103N mutant strain. 2006 Bioorganic & medicinal chemistry letters Abstract HIV K103N 176 181 NNRTI 78 114 16503141 Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant. Extensive SAR investigation led to potent compounds, with nanomolar activity on K103N, and orally bioavailable in rats. 2006 Bioorganic & medicinal chemistry letters Abstract HIV K103N 80 85 16504235 The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. In the absence of efavirenz, the fitness hierarchy was G190S < G190A < K103N < wild-type. 2006 Virology Abstract HIV G190A;G190S;K103N 63;55;71 68;60;76 16504235 The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. It also suggests that high concentrations of efavirenz are unlikely to favor the selection of G190S clinically. 2006 Virology Abstract HIV G190S 94 99 16504235 The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. The fitness reduction of G190S relative to K103N was less evident at high efavirenz concentrations, although K103N still replicated more efficiently. 2006 Virology Abstract HIV G190S;K103N;K103N 25;43;109 30;48;114 16504235 The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. We evaluated the replication efficiency of the HIV reverse transcriptase (RT) mutants K103N, G190A, and G190S, which confer resistance to the non-nucleoside RT inhibitor efavirenz, using growth competition assays in cell culture. 2006 Virology Abstract HIV G190A;G190S;K103N 93;104;86 98;109;91 RT;RT;RT 51;74;157 72;76;159 16504560 Structural and dynamical properties of different protonated states of mutant HIV-1 protease complexed with the saquinavir inhibitor studied by molecular dynamics simulations. To understand the basis of drug resistance, particularly of the HIV-1 PR, three molecular dynamics (MD) simulations of HIV-1 PR mutant species, G48V, complexed with saquinavir (SQV) in explicit aqueous solution with three protonation states, diprotonation on Asp25 and Asp25' (Di-pro) and monoprotonation on each Asp residue (Mono-25 and Mono-25'). 2006 Journal of molecular graphics & modelling Abstract HIV G48V 144 148 Asp;Asp;Asp;PR;PR 259;269;313;70;125 262;272;316;72;127 16508951 Restrained molecular dynamics simulations of HIV-1 protease: the first step in validating a new target for drug design. To test the anticorrelated relationship that was recently displayed in conventional molecular dynamics (MD) simulations, several different restrained MD simulations on a wild type and on the V82F/I84V drug-resistant mutant of HIV-1 protease were performed. 2006 Biopolymers Abstract HIV I84V;V82F 196;191 200;195 PR 232 240 16511398 Transmission of human immunodeficiency virus type 1 nevirapine resistance mutation K103N from a treatment-naive mother to her child. In this report, a treatment-naive mother transmitted HIV-1 resistance mutation K103N against nevirapine to her child. 2006 The Pediatric infectious disease journal Abstract HIV K103N 79 84 16513416 An additive/subtractive genotypic score as a determinant of the virological response to didanosine in HIV-1 infected patients. RESULTS: Changes at three codons (M41L, L210W, T215Y/F/D/C/E) were associated with a worse VR and three mutations (K70R, M184V, K219Q) with a better VR. 2006 Journal of clinical virology Abstract HIV K219Q;K70R;L210W;M184V;M41L;T215C;T215D;T215E;T215F;T215Y 128;115;40;121;34;47;47;47;47;47 133;119;45;126;38;60;60;60;60;60 16513416 An additive/subtractive genotypic score as a determinant of the virological response to didanosine in HIV-1 infected patients. The strongest association with the VR was obtained with the score M41L+L210W+T215Y/F/D/C/E-K70R-K219Q. 2006 Journal of clinical virology Abstract HIV K219Q;K70R;L210W;M41L;T215C;T215D;T215E;T215F;T215Y 96;91;71;66;77;77;77;77;77 101;95;76;70;90;90;90;90;90 16514300 Selection and persistence of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 in patients starting and stopping non-nucleoside therapy. OBJECTIVE: To develop a high-throughput, real-time reverse transcriptase (RT) polymerase chain reaction (PCR) assay to quantify non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant variants K103N (AAT or AAC alleles) at frequencies as low as 0.1%, and to apply this to monitor these variants before, during, and after NNRTI therapy. 2006 AIDS (London, England) Abstract HIV K103N 202 207 NNRTI;RT;Pol;NNRTI;NNRTI;RT 128;51;78;176;330;74 164;72;88;181;335;76 16514300 Selection and persistence of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 in patients starting and stopping non-nucleoside therapy. The rate of decay of K103N variants after stopping NNRTI therapy was highly variable. 2006 AIDS (London, England) Abstract HIV K103N 21 26 NNRTI 51 56 16527535 Non-infectious fluorimetric assay for phenotyping of drug-resistant HIV proteinase mutants. RESULTS: We cloned a set of GFP-PR reporters, some of which possess a simple, well-defined drug-resistant PR mutant (G48V L90M, V82A, A71V V82T I84V, D30N, K45I); another four complex PR mutants were obtained from patients undergoing HAART. 2006 Journal of clinical virology Abstract HIV A71V;D30N;G48V;I84V;K45I;L90M;V82A;V82T 134;150;117;144;156;122;128;139 138;154;122;148;160;126;132;143 PR;PR;PR 32;106;184 34;108;186 16533835 Gated binding of ligands to HIV-1 protease: Brownian dynamics simulations in a coarse-grained model. The computed gated association rate constants of three protease mutants, G48V/V82A/I84V/L90M, G48V, and L90M with three drugs, amprenavir, indinavir, and saquinavir, yield good agreements with experiments. 2006 Biophysical journal Abstract HIV G48V;I84V;L90M;V82A;G48V;L90M 73;83;88;78;94;104 77;87;92;82;98;108 PR 55 63 16533835 Gated binding of ligands to HIV-1 protease: Brownian dynamics simulations in a coarse-grained model. The simulations suggest that the flap flexibility and the opening frequency of the wild-type, the G48V and L90M mutants are similar, but the flaps of the variant G48V/V82A/I84V/L90M open less frequently, resulting in a lower gated rate constant. 2006 Biophysical journal Abstract HIV G48V;I84V;L90M;V82A;G48V;L90M 162;172;177;167;98;107 166;176;181;171;102;111 16540937 The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes. A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I82T;V106M 42;70 46;75 16540937 The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I82A;L210W;P225H;Q151M;V108I;V118I 48;137;181;111;73;92 52;142;186;116;78;97 16545016 Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations. One wild-type clone had reduced susceptibility to NVP, delavirdine (DLV), and efavirenz (EFV), one clone with K103N was susceptible to all three NNRTIs, and one clone with G190A had extreme hypersusceptibility to DLV. 2006 AIDS research and human retroviruses Abstract HIV G190A;K103N 172;110 177;115 NNRTI 145 151 16545016 Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations. Six clones had no NNRTI resistance-associated mutations ("wild type"), eight had K103N, nine had Y181C, five had G190A, and one had Y181S. 2006 AIDS research and human retroviruses Abstract HIV G190A;K103N;Y181C;Y181S 113;81;97;132 118;86;102;137 NNRTI 18 23 16545016 Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations. Three unusual HIV-1 RT amino acid substitutions may have contributed to the unexpected phenotypes of the clones: I31T, N136S, and N265D. 2006 AIDS research and human retroviruses Abstract HIV I31T;N136S;N265D 113;119;130 117;124;135 RT 20 22 16549962 Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study). METHODS: This 48-week, open-label pilot study randomly assigned HIV-infected patients receiving lamivudine-containing HAART and harbouring the M184V mutation to monotherapy with lamivudine 300 mg once daily (lamivudine group) or the discontinuation of all antiretroviral drugs (TI group). 2006 AIDS (London, England) Abstract HIV M184V 143 148 HIV infections 64 76 16549966 Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. BACKGROUND: It has been suggested that mutations of R77A and R80A in the HIV-1 viral protein R (Vpr) impair its proapoptotic activity and that a naturally occurring R77Q variation is associated with non-progressive HIV-1 infection. 2006 AIDS (London, England) Abstract HIV R77A;R77Q;R80A 52;165;61 56;169;65 Vpr 96 99 16549966 Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. CONCLUSIONS: The observation that Vpr R77Q reduces the cytopathicity of R5-tropic HIV-1 in lymphoid tissues supports a role in non-progressive HIV-1 infection but the attenuating effects might be dependent on the viral subtype and coreceptor tropism. 2006 AIDS (London, England) Abstract HIV R77Q 38 42 Vpr 34 37 16549966 Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. Mutation of R77Q and R80A reduced apoptosis of HIV-1-infected cells in ex vivo-infected HLT independently of the viral coreceptor tropism. 2006 AIDS (London, England) Abstract HIV R77Q;R80A 12;21 16;25 HIV infections 47 61 16549966 Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. RATIONALE: To assess the effect of Vpr R77Q, R77A and R80A mutations on the efficiency of CCR5(R5)- and CXCR4(X4)-tropic HIV-1 replication and cytopathicity in human lymphoid tissue (HLT). 2006 AIDS (London, England) Abstract HIV R77A;R77Q;R80A 45;39;54 49;43;58 Vpr 35 38 16549966 Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. RESULTS: The R5-tropic HIV-1 Vpr mutants replicated with slightly (R77A, R77Q) to moderately (R80A) reduced efficiency in ex vivo-infected HLT and macrophages. 2006 AIDS (London, England) Abstract HIV R77A;R77Q;R80A 67;73;94 71;77;98 Vpr 29 32 16553322 Study of antiretroviral mutants in HIV patients with treatment failures and the effect of risk factors in the virological failures. The most frequent mutations were M41L, M184V, and T215FY in RT and L62PI, L10FIRV and M36I in PT. 2005 Revista do Instituto de Medicina Tropical de Sao Paulo Abstract HIV L10F;L10I;L10R;L10V;L62I;L62P;M184V;M36I;M41L;T215F;T215Y 74;74;74;74;67;67;39;86;33;50;50 81;81;81;81;72;72;44;90;37;56;56 RT 60 62 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. Although its prevalence is increasing with the use of this drug, clinical and genotypic correlates of K65R occurrence have yet to be fully identified. 2006 Journal of medical virology Abstract HIV K65R 102 106 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. Among genotypic correlates, the presence of M184V and NAMs seems to be protective for the emergence of K65R, while a strong positive correlation was found with the Q151M complex mutation. 2006 Journal of medical virology Abstract HIV K65R;M184V;Q151M 103;44;164 107;49;169 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. Conversely, long 3TC exposure, and the presence of M184V or NAMs seem to be protective. 2006 Journal of medical virology Abstract HIV M184V 51 56 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. However, exposure to abacavir and/or efavirenz, presence of Q151M and/or L100I, and prior AIDS may favor the selection of this mutation. 2006 Journal of medical virology Abstract HIV L100I;Q151M 73;60 78;65 AIDS 90 94 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. Moreover, the L100I mutation was independently associated with a higher probability of presenting K65R. 2006 Journal of medical virology Abstract HIV K65R;L100I 98;14 102;19 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. Out of 1392 GRT performed for 771 patients, 12 TDF-naive patients had the K65R mutation with an overall prevalence of 1.6%. 2006 Journal of medical virology Abstract HIV K65R 74 78 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. Previous AIDS, the use of abacavir, and treatment with efavirenz at GRT were independently associated with a greater risk of expressing K65R, while patients with longer exposure to lamivudine were less likely to present the mutation. 2006 Journal of medical virology Abstract HIV K65R 136 140 AIDS 9 13 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. The mutation RT-K65R confers resistance to tenofovir (TDF). 2006 Journal of medical virology Abstract HIV K65R 16 20 RT 13 15 16555278 Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir. The selection of mutation K65R in patients failing without TDF is rare. 2006 Journal of medical virology Abstract HIV K65R 26 30 16555280 Effects of drug resistance on viral load in patients failing antiretroviral therapy. Certain reverse transcriptase mutations such as M184V/I, K70R, V108I, and protease mutations such as L33FIV, M84V, and M36I were associated with reduced viral load. 2006 Journal of medical virology Abstract HIV K70R;L33F;L33I;L33V;M184I;M184V;M36I;M84V;V108I 57;101;101;101;48;48;119;109;63 61;107;107;107;55;55;123;113;68 RT;PR 8;74 29;82 16563858 Natural polymorphism in protease and reverse transcriptase genes and in vitro antiretroviral drug susceptibilities of non-B HIV-1 strains from treatment-naive patients. Some mutations could be associated with decreased in vitro susceptibility: 1 of 3 strains only with mutations M46I/L in protease, 1/2 A98S, K101N, V108I, V179I, and P236L in reverse transcriptase. 2006 Journal of clinical virology Abstract HIV K101N;M46I;M46L;P236L;V108I;V179I 140;110;110;165;147;154 145;116;116;170;152;159 RT;PR 174;120 195;128 16569415 Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. Compared to wild-type PR, PR(F53L) showed lower (15%) catalytic efficiency, 20-fold weaker inhibition by the clinical drug indinavir, and reduced dimer stability, while the inhibition constants of two peptide analog inhibitors were slightly lower than those for PR. 2006 Journal of molecular biology Abstract HIV F53L 29 33 PR;PR;PR 22;26;262 24;28;264 16569415 Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. The altered flap interactions in the unliganded form of PR(F53L) suggest a distinct mechanism for drug resistance, which has not been observed in other common drug-resistant mutants. 2006 Journal of molecular biology Abstract HIV F53L 59 63 PR 56 58 16569415 Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. The changes in interactions between the flaps agreed with the reduced stability of PR(F53L) relative to wild-type PR. 2006 Journal of molecular biology Abstract HIV F53L 86 90 PR;PR 83;114 85;116 16569415 Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. The crystal structure of PR(F53L) was determined in the unliganded form at 1.35 Angstrom resolution in space group P4(1)2(1)2. 2006 Journal of molecular biology Abstract HIV F53L 28 32 PR 25 27 16569415 Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. The mutation F53L arising from antiretroviral therapy was introduced into the flexible flap region of the wild-type PR to study its effect and potential role in developing drug resistance. 2006 Journal of molecular biology Abstract HIV F53L 13 17 PR 116 118 16569415 Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. The tips of the flaps in PR(F53L) had a wider separation than in unliganded wild-type PR, probably due to the absence of hydrophobic interactions of the side-chains of Phe53 and Ile50'. 2006 Journal of molecular biology Abstract HIV F53L 28 32 PR;PR 25;86 27;88 16571788 Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. In a previous study, we reported that an HIV-1 mutant containing two substitutions in CA (Q63A/67A) was unusual in that it was poorly infectious yet synthesized normal levels of viral DNA. 2006 Journal of virology Abstract HIV Q63A 90 94 Capsid 86 88 16571788 Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. Isolation of PICs from acutely infected cells revealed that the Q63A/Q67A mutant produces protein-DNA complexes similar to wild-type in yield and overall composition, but these PICs contained elevated levels of CA and were impaired for integration in vitro. 2006 Journal of virology Abstract HIV Q63A;Q67A 64;69 68;73 Capsid 211 213 16571788 Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. Quantitative analysis of viral DNA synthesis from infected cells by Southern blotting and real-time PCR revealed that the Q63A/Q67A mutant is impaired in the synthesis of one-long terminal repeat (1-LTR) and 2-LTR circles. 2006 Journal of virology Abstract HIV Q63A;Q67A 122;127 126;131 LTR;LTR;LTR 175;199;210 195;202;213 16586357 Frequency and treatment-related predictors of thymidine-analogue mutation patterns in HIV-1 isolates after unsuccessful antiretroviral therapy. TAM pattern 1, which included M41L and L210W and excluded K70R and is coupled with more-extensive cross-resistance to drugs, became the most frequent pattern after 1996. 2006 The Journal of infectious diseases Abstract HIV K70R;L210W;M41L 58;39;30 62;44;34 16603505 Development of a novel GFP-based ratiometric excitation and emission pH indicator for intracellular studies. We report on the development of the F64L/S65T/T203Y/L231H GFP mutant (E2GFP) as an effective ratiometric pH indicator for intracellular studies. 2006 Biophysical journal Abstract HIV F64L;L231H;S65T;T203Y 36;52;41;46 40;57;45;51 16603533 Biological characterization of human immunodeficiency virus type 1 subtype C protease carrying indinavir drug-resistance mutations. A series of recombinant subtype C and B viruses was constructed carrying indinavir (IDV)-resistance mutations (M46V, I54V, V82A and L90M) and their susceptibility to six FDA-approved protease inhibitor compounds (amprenavir, indinavir, lopinavir, ritonavir, saquinavir and nelfinavir) was determined. 2006 The Journal of general virology Abstract HIV I54V;L90M;M46V;V82A 117;132;111;123 121;136;115;127 PR 183 191 16603849 Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. CONCLUSION: Different combinations of V118I, H208Y, and T215Y produce NNRTI hypersusceptibility. 2006 AIDS (London, England) Abstract HIV H208Y;T215Y;V118I 45;56;38 50;61;43 NNRTI 70 75 16603849 Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. In addition, H208Y/T215Y, V118I/T215Y, and V118I/H208Y/T215Y were hypersusceptible to delavirdine and nevirapine. 2006 AIDS (London, England) Abstract HIV H208Y;T215Y;V118I;H208Y;T215Y;T215Y;V118I 49;55;43;13;19;32;26 54;60;48;18;24;37;31 16603849 Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. RESULTS: The single mutations V118I, H208Y, and T215Y did not show hypersusceptibility to efavirenz with mean fold-change of 0.58, 0.55, and 0.70, respectively (P < 0.01 and P = 0.12). 2006 AIDS (London, England) Abstract HIV H208Y;T215Y;V118I 37;48;30 42;53;35 16603849 Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. The genetic basis for NNRTI hypersusceptibility was partly defined in our earlier analyses of a paired genotype-phenotype dataset of viral isolates from treatment-experienced patients, in which we identified reverse transcriptase mutations V118I, H208Y, and T215Y as being strongly associated with NNRTI hypersusceptibility. 2006 AIDS (London, England) Abstract HIV H208Y;T215Y;V118I 247;258;240 252;263;245 RT;NNRTI;NNRTI 208;22;298 229;27;303 16603849 Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. The H208Y/T215Y and V118I/H208Y/T215Y mutants showed marked hypersusceptibility to efavirenz, having mean fold-change values of 0.27 and 0.20, respectively (P < 0.001). 2006 AIDS (London, England) Abstract HIV H208Y;T215Y;V118I;H208Y;T215Y 26;32;20;4;10 31;37;25;9;15 16603849 Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. The V118I/T215Y mutant is hypersusceptible to delavirdine and nevirapine without reduced replication capacity, whereas the H208Y/T215Y and V118I/H208Y/T215Y mutants are hypersusceptible to all NNRTI and show impaired replication. 2006 AIDS (London, England) Abstract HIV H208Y;T215Y;V118I;H208Y;T215Y;T215Y;V118I 145;151;139;123;10;129;4 150;156;144;128;15;134;9 NNRTI 193 198 16603849 Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors. The V118I/T215Y mutant was not replication impaired; whereas H208Y/T215Y and V118I/H208Y/T215Y had significantly (P < 0.01) reduced replication capacities of 40 and 35% of wild-type, respectively. 2006 AIDS (London, England) Abstract HIV H208Y;T215Y;V118I;H208Y;T215Y;T215Y;V118I 83;89;77;61;67;10;4 88;94;82;66;72;15;9 16603851 Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. CONCLUSIONS: K103N resistant variants were present in almost all women at 6 weeks post-sd-NVP but declined rapidly over time. 2006 AIDS (London, England) Abstract HIV K103N 13 18 16603851 Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. DESIGN AND METHODS: We measured the frequency of K103N mutants among a cohort of HIV-1-infected pregnant women recruited at an out-patient clinic in Johannesburg, South Africa. 2006 AIDS (London, England) Abstract HIV K103N 49 54 HIV infections 81 95 16603851 Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. OBJECTIVES: Single-dose nevirapine (sd-NVP) for prevention of mother-to-child HIV-1 transmission is associated with selection of resistant viral variants, particularly the Lysine (K) to Asparagine (N) mutation at codon 103 (K103N) of reverse transcriptase. 2006 AIDS (London, England) Abstract HIV K103N 224 229 RT 234 255 16603851 Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. Quantification of K103N mutants in maternal plasma viral RNA and cellular DNA was done using an allele-specific real-time polymerase chain reaction assay capable of detecting codons AAC and AAT if their frequency was > 0.002 of the total viral population. 2006 AIDS (London, England) Abstract HIV K103N 18 23 Pol 122 132 16603851 Decay of K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to reduce mother-to-child HIV transmission. RESULTS: Using the allele-specific assay, 87.1% (27/31) of RNA samples and 52.3% (23/44) of DNA samples collected 6 weeks after sd-NVP had detectable K103N variants. 2006 AIDS (London, England) Abstract HIV K103N 150 155 16603864 Prevalence of the HIV-1 protease mutation I47A in clinical practice and association with lopinavir resistance. Only four out of 1859 specimens (0.2%) sent for drug resistance testing (219 drug-naive and 1650 antiretroviral-experienced) showed I47A. 2006 AIDS (London, England) Abstract HIV I47A 132 136 16610780 Biosensor-based kinetic characterization of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors. This initial study was performed with HIV-1 reverse transcriptase mutant K103N, the phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs licensed for clinical use: nevirapine, delavirdine, and efavirenz. 2006 Journal of medicinal chemistry Abstract HIV K103N 73 78 RT;NNRTI 44;151 65;157 16610781 Interaction kinetic characterization of HIV-1 reverse transcriptase non-nucleoside inhibitor resistance. The K103N and the L100I substitutions were found to facilitate both the entry of the inhibitor into the binding pocket as well as its exit, in contrast to what has been reported elsewhere. 2006 Journal of medicinal chemistry Abstract HIV K103N;L100I 4;18 9;23 16610781 Interaction kinetic characterization of HIV-1 reverse transcriptase non-nucleoside inhibitor resistance. The Y181C, V108I, and P225H substitutions affected primarily the association and dissociation rate constants, while the K103N and the L100I substitutions also influenced the equilibrium between the two forms of the free enzyme. 2006 Journal of medicinal chemistry Abstract HIV K103N;L100I;P225H;V108I;Y181C 120;134;22;11;4 125;139;27;16;9 16616962 Discovery of TSAO derivatives with an unusual HIV-1 activity/resistance profile. A mixture of wild-type and V106V/A or L234L/I mutations were found in the RT of some, but not all compound 3-resistant virus strains. 2006 Antiviral research Abstract HIV L234I;L234L;V106A;V106V 38;38;27;27 45;45;34;34 RT 74 76 16616962 Discovery of TSAO derivatives with an unusual HIV-1 activity/resistance profile. Compound 3 does not select for the TSAO-specific E138K mutation in the RT. 2006 Antiviral research Abstract HIV E138K 49 54 RT 71 73 16616962 Discovery of TSAO derivatives with an unusual HIV-1 activity/resistance profile. However, the compound markedly lost its antiviral potential against a variety of virus strains that contain NNRTI-characteristic mutations in RT including E138K. 2006 Antiviral research Abstract HIV E138K 155 160 NNRTI;RT 108;142 113;144 16623640 Susceptibility to antiretroviral drugs of CRF01_AE, CRF02_AG, and subtype C viruses from untreated patients of Africa and Asia: comparative genotypic and phenotypic data. CRF01_AE isolates are sensitive to NRTIs and NNRTIs with the exception of one isolate that exhibits a decreased susceptibility to NNRTIs associated with a I135T substitution in RT. 2006 AIDS research and human retroviruses Abstract HIV I135T 155 160 NNRTI;NNRTI;NRTI;RT 45;130;35;177 51;136;40;179 16623640 Susceptibility to antiretroviral drugs of CRF01_AE, CRF02_AG, and subtype C viruses from untreated patients of Africa and Asia: comparative genotypic and phenotypic data. CRF02_AG and subtype C viruses are sensitive to NRTIs and NNRTIs but some CRF02_AG isolates tend to be resistant to abacavir, potentially related to associated substitutions of RT at positions 123 (D123N) plus 135 (I135V). 2006 AIDS research and human retroviruses Abstract HIV D123N;I135V 198;215 203;220 NNRTI;NRTI;RT 58;48;177 64;53;179 16623640 Susceptibility to antiretroviral drugs of CRF01_AE, CRF02_AG, and subtype C viruses from untreated patients of Africa and Asia: comparative genotypic and phenotypic data. The role of substitutions in prot at positions of secondary resistance mutations 20, 36, 63, and 82 is raised with a potentially crucial role of the V82I substitution. 2006 AIDS research and human retroviruses Abstract HIV V82I 149 153 16628575 Trends in drug resistance mutations in antiretroviral-naive intravenous drug users of Rio de Janeiro. Genotypic analysis revealed the presence of PR primary L90M, D30N, M46I, and V82A mutations in 7.9% of the post-HAART group, and a high frequency of secondary mutations (84.2%). 2006 Journal of medical virology Abstract HIV D30N;L90M;M46I;V82A 61;55;67;77 65;59;71;81 PR 44 46 16632914 Analysis of a long-term discrepancy in drug-targeted genes in plasma HIV-1 RNA and PBMC HIV-1 DNA in the same patient. In contrast, in proviral DNA, no drug resistance-associated mutations were found in the RT region, and mutations such as L90L/M were only infrequently present in the Pro region. 2006 Japanese journal of infectious diseases Abstract HIV L90L;L90M 121;121 127;127 RT 88 90 16632914 Analysis of a long-term discrepancy in drug-targeted genes in plasma HIV-1 RNA and PBMC HIV-1 DNA in the same patient. In plasma HIV-1 RNA, D67N, K70R, T215Y, and Y188L were present in the reverse transcriptase (RT) region, and two primary mutations, I84V and L90M, were noted in the protease (Pro) region. 2006 Japanese journal of infectious diseases Abstract HIV D67N;I84V;K70R;L90M;T215Y;Y188L 21;132;27;141;33;44 25;136;31;145;38;49 RT;PR;RT 70;165;93 91;173;95 16634628 Analysis of HIV-1 CRF_01 A/E protease inhibitor resistance: structural determinants for maintaining sensitivity and developing resistance to atazanavir. This structure also explains why the I50L and I84V mutations are important in decreasing the binding affinity of atazanavir. 2006 Biochemistry Abstract HIV I50L;I84V 37;46 41;50 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. HIV-1 with TAMs shows reduced susceptibility to all NRTIs, most notably AZT, whereas HIV-1 with K65R shows reduced susceptibility to all NRTIs except AZT. 2006 Antiviral therapy Abstract HIV K65R 96 100 NRTI;NRTI 52;137 57;142 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. However, when present together, K65R can restore susceptibility to AZT. 2006 Antiviral therapy Abstract HIV K65R 32 36 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. K65R and TAMs rarely occur together in patients. 2006 Antiviral therapy Abstract HIV K65R 0 4 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. K65R mediated decreased binding/incorporation of TFV and AZT (increased Ki/Km of 7.1- and 4.3-fold, respectively), but also decreased excision of TFV and AZT (0.7- and 0.3-fold, respectively) when compared with wild-type RT. 2006 Antiviral therapy Abstract HIV K65R 0 4 RT 221 223 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. Molecular modelling studies suggest that K65R creates additional hydrogen bonds that reduce the conformational mobility of RT, resulting in reduced polymerization and excision. 2006 Antiviral therapy Abstract HIV K65R 41 45 RT 123 125 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. The HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir (TFV), abacavir, didanosine and stavudine can select for K65R, whereas zidovudine (AZT) and stavudine can select for thymidine analogue mutations (TAMs) in HIV-1 reverse transcriptase (RT). 2006 Antiviral therapy Abstract HIV K65R 129 133 NRTI;RT;NRTI;RT 10;234;55;257 42;255;60;259 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. Thus, consistent with clinical HIV-1 genotyping data, there appears to be no net NRTI resistance benefit for TAMs and K65R to develop together in patients taking AZT and TFV disoproxil fumarate, where the TAM pathway alone provides the greatest resistance for both drugs. 2006 Antiviral therapy Abstract HIV K65R 118 122 NRTI 81 85 16640096 The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. When these mutations were combined, K65R reversed TAM-mediated AZT resistance by strongly reducing AZT excision. 2006 Antiviral therapy Abstract HIV K65R 36 40 16640104 Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients. Any single type-1 thymidine analogue mutation (TAM; M41L, L210W, T215Y) had a negative effort on the change in HIV RNA at 6 months, whereas among type-2 TAMs (D67N, K70R, K219Q), only D67N showed a trend for a negative effect. 2006 Antiviral therapy Abstract HIV D67N;D67N;K219Q;K70R;L210W;M41L;T215Y 159;184;171;165;58;52;65 163;188;176;169;63;56;70 16640104 Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients. Conversely, M184V showed a protective effect. 2006 Antiviral therapy Abstract HIV M184V 12 17 16640104 Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients. In 17 genotypic tests available at failure, no K65R mutation was detected, whereas a trend for an increasing prevalence of d4T-associated mutations was found. 2006 Antiviral therapy Abstract HIV K65R 47 51 16640104 Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients. Presence of M184V mutation was related with a greater reduction in HIV RNA during d4T/TDF exposure. 2006 Antiviral therapy Abstract HIV M184V 12 17 16641095 Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission. Allele-specific PCR analysis for the two most common NVP resistance mutations (K103N and Y181C) detected NVP-resistant variants in most (16 of 21) samples that were negative for NVP resistance by standard genotype, at levels ranging from 0.1% to 20% 1 yr after treatment. 2006 Proc Natl Acad Sci U S A Abstract HIV K103N;Y181C 79;89 85;94 16641261 Cyclophilin A renders human immunodeficiency virus type 1 sensitive to Old World monkey but not human TRIM5 alpha antiviral activity. We use an HIV-1 cyclophilin A binding mutant (CA G89V) to show that cyclophilin A has different roles in restriction by Old World monkey TRIM5alpha and owl monkey TRIM-Cyp. 2006 Journal of virology Abstract HIV G89V 49 53 Capsid 46 48 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. Among >60,000 clinical samples submitted for genotype analysis that contained one or more NRTI resistance mutations, the frequency of K65R increased from 0.4% in 1998 to 3.6% in 2003. 2006 Journal of virology Abstract HIV K65R 134 138 NRTI 90 94 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. Among samples with K65R, a strong negative association was evident with the TAMs M41L, D67N, L210W, T215Y/F, and K219Q/E (P<0.005) but not with other NRTI mutations, including the Q151M complex. 2006 Journal of virology Abstract HIV D67N;K219E;K219Q;K65R;L210W;M41L;Q151M;T215F;T215Y 87;113;113;19;93;81;180;100;100 91;120;120;23;98;85;185;107;107 NRTI 150 154 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. In addition, TAMs antagonized the phenotypic effect of K65R, reducing resistance to tenofovir, abacavir, 2',3'-dideoxycytidine, dideoxyinosine, and stavudine. 2006 Journal of virology Abstract HIV K65R 55 59 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. In conclusion, K65R and TAMs exhibit bidirectional phenotypic antagonism. 2006 Journal of virology Abstract HIV K65R 15 19 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. In recent clinical trials, the K65R mutation has emerged frequently in patients experiencing virologic failure on antiretroviral combinations that do not include 3'-azidothymidine (AZT). 2006 Journal of virology Abstract HIV K65R 31 35 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. K65R reduced AZT resistance from >50-fold to <2.5-fold in both backgrounds. 2006 Journal of virology Abstract HIV K65R 0 4 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. The K65R mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is selected in vitro by many D-nucleoside analog RT inhibitors (NRTI) but has been rarely detected in treated patients. 2006 Journal of virology Abstract HIV K65R 4 8 RT;NRTI;RT;RT 65;156;88;141 86;160;90;143 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. This antagonism likely explains the negative association of these mutations in genotype databases, the rare emergence of K65R with antiretroviral therapies that contain AZT, and its more frequent emergence with combinations that exclude AZT. 2006 Journal of virology Abstract HIV K65R 121 125 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. This suggested that K65R and TAMs are antagonistic. 2006 Journal of virology Abstract HIV K65R 20 24 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. To gain insight, we examined trends in the frequency of K65R in a large genotype database, the association of K65R with thymidine analog mutations (TAMs) and other NRTI mutations, and the viral susceptibility profile of HIV-1 with K65R alone and in combination with TAMs. 2006 Journal of virology Abstract HIV K65R;K65R;K65R 56;110;231 60;114;235 NRTI 164 168 16641288 The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. To test this possibility, we generated recombinant HIV-1 encoding K65R in two different TAM backgrounds: M41L/L210W/T215Y and D67N/K70R/T215F/K219Q. 2006 Journal of virology Abstract HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y;K65R 126;142;131;110;105;136;116;66 130;147;135;115;109;141;121;70 16644557 Design of nevirapine derivatives insensitive to the K103N and Y181C HIV-1 reverse transcriptase mutants. 124 Compounds having a GoldScore higher than that of nevirapine (55.00 and 52.00 for K103N and Y181C mutants, respectively) were first retrieved and submitted to a topological analysis with the SILVER program. 2006 SAR and QSAR in environmental research Abstract HIV K103N;Y181C 85;95 90;100 16644557 Design of nevirapine derivatives insensitive to the K103N and Y181C HIV-1 reverse transcriptase mutants. Its efficiency is limited by drug resistant mutations, such as K103N and Y181C, so, the aim of this work was to design novel nevirapine analogues insensitive to the K103N and Y181C HIV-1 RT. 2006 SAR and QSAR in environmental research Abstract HIV K103N;K103N;Y181C;Y181C 63;165;73;175 68;170;78;180 RT 187 189 16672276 Structural analysis of a mutant of the HIV-1 integrase zinc finger domain that forms a single conformation. In the present study, structural analysis of a mutant of IN(1-55), Y15A, by NMR spectroscopy indicated that the mutant protein folds correctly but takes only the E form. 2006 Journal of biochemistry Abstract HIV Y15A 67 71 IN 57 59 16672276 Structural analysis of a mutant of the HIV-1 integrase zinc finger domain that forms a single conformation. Since the Y15A mutation abrogates the HIV-1 infectivity, Y15 might have some important role in the full-length integrase activity during the virus infection cycle. 2006 Journal of biochemistry Abstract HIV Y15A 10 14 IN 111 120 16699009 Gag regulates association of human immunodeficiency virus type 1 envelope with detergent-resistant membranes. A mutation in the p17 matrix (L30E) domain in Gag (Gag L30E) that abrogates envelope incorporation onto virions also eliminated envelope association with DRMs in 293T cells and in the T-cell line, MOLT 4. 2006 Journal of virology Abstract HIV L30E;L30E 30;55 34;59 Env;Env;Matrix;Gag;Gag 76;128;22;46;51 84;136;28;49;54 16706626 HIV-1 genetic diversity and genotypic drug susceptibility in the Republic of Georgia. This "V77I haplotype" marks one particular genetic lineage of the epidemic in the former Soviet Union. 2006 AIDS research and human retroviruses Abstract HIV V77I 6 10 16706626 HIV-1 genetic diversity and genotypic drug susceptibility in the Republic of Georgia. Twelve of the subtype A strains (25%) contained the secondary protease inhibitor mutation V77I and 9 also had two other silent mutations. 2006 AIDS research and human retroviruses Abstract HIV V77I 90 94 PR 62 70 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Analysis of 2-LTR circle junctions revealed that F61W and F61Y mutants generated increased aberrant circle junctions. 2006 Nucleic acids research Abstract HIV F61W;F61Y 49;58 53;62 LTR 14 17 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Circle junctions corresponding to F61Y included 3'-PPT insertions suggesting ribonuclease H defect. 2006 Nucleic acids research Abstract HIV F61Y 34 38 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In assays measuring cleavage at the RNA/DNA junction to remove the PPT primer, all mutants were significantly affected with F61Y and F61A being most severely impaired. 2006 Nucleic acids research Abstract HIV F61A;F61Y 133;124 137;128 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In vitro assays mimicking PPT primer generation indicated that F61L, F61W and F61Y mutant RTs were unaffected, while F61A mutant cleaved both at PPT/U3 junction and at +6 with similar efficiencies. 2006 Nucleic acids research Abstract HIV F61A;F61L;F61W;F61Y 117;63;69;78 121;67;73;82 RT 90 93 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Measuring replication intermediates in infected cells did not reveal a specific block as all mutants displayed reduced DNA synthesis (wild-type>F61L>F61W>F61Y>F61A). 2006 Nucleic acids research Abstract HIV F61A;F61L;F61W;F61Y 159;144;149;154 163;148;153;158 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. We reported previously that substitutions F61L, F61W, F61Y and F61A in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase affect strand displacement synthesis [T. 2006 Nucleic acids research Abstract HIV F61A;F61L;F61W;F61Y 63;42;48;54 67;46;52;58 RT 115 136 16723586 Impact of human immunodeficiency virus type 1 subtype C on drug resistance mutations in patients from Botswana failing a nelfinavir-containing regimen. Among 16 human immunodeficiency virus-infected (subtype C) Batswana patients who failed nelfinavir (NFV)-containing regimens, the most prevalent mutation observed was D30N (54%), followed by L90M (31%). 2006 Antimicrobial agents and chemotherapy Abstract HIV D30N;L90M 167;191 171;195 16723586 Impact of human immunodeficiency virus type 1 subtype C on drug resistance mutations in patients from Botswana failing a nelfinavir-containing regimen. L89I, K20T/I, and E35D polymorphic changes were also identified. 2006 Antimicrobial agents and chemotherapy Abstract HIV E35D;K20I;K20T;L89I 18;6;6;0 22;12;12;4 16724949 Insertions and deletions in HIV-1 reverse transcriptase: consequences for drug resistance and viral fitness. in the presence of Q151M), the effects of the deletion are not fully understood. 2006 Current pharmaceutical design Abstract HIV Q151M 19 24 16724949 Insertions and deletions in HIV-1 reverse transcriptase: consequences for drug resistance and viral fitness. T215Y) in the viral RT confers an ATP-dependent phosphorolytic activity that facilitates the removal of the inhibitor from primers terminated with zidovudine or stavudine. 2006 Current pharmaceutical design Abstract HIV T215Y 0 5 RT 20 22 16731910 3-O-(3',3'-dimethysuccinyl) betulinic acid inhibits maturation of the human immunodeficiency virus type 1 Gag precursor assembled in vitro. Analysis of a PA-457-resistant mutant, A1V, in this system pointed to more rapid cleavage as a possible mechanism for resistance. 2006 Journal of virology Abstract HIV A1V 39 42 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. A high level of resistance was only seen in mutants containing the 19I/A22V and p1/p6 mutations. 2006 Journal of virology Abstract HIV A22V 71 75 Gag 83 85 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. Longitudinal analysis revealed that the P63L/A71V/I93L changes were present prior to PI therapy. 2006 Journal of virology Abstract HIV A71V;I93L;P63L 45;50;40 49;54;44 PI 85 87 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. Population-based sequence analysis revealed the presence of a variant of human immunodeficiency virus type 1 (HIV-1) containing an insertion of amino acid Ile in the protease gene at codon 19 (19I) and amino acid substitutions in the protease at codons 21 (E21D) and 22 (A22V) along with multiple mutations associated with drug resistance, M46I/P63L/A71V/I84V/I93L, in a patient who had failed protease inhibitor (PI) therapy. 2006 Journal of virology Abstract HIV A71V;I84V;I93L;M46I;P63L;A22V;E21D 350;355;360;340;345;271;257 354;359;364;344;349;275;261 PR;PR;PR;PI 166;234;394;414 174;242;402;416 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. The combination of the 19I/A22V mutations may be associated with PI resistance; however, the drug resistance may be caused by the presence of a unique set of mutations in the p1/p6 mutations. 2006 Journal of virology Abstract HIV A22V 27 31 Gag;PI 178;65 180;67 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. The E21D mutation contributes to replication fitness rather than drug resistance. 2006 Journal of virology Abstract HIV E21D 4 8 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. The E21D mutation enhanced viral replication. 2006 Journal of virology Abstract HIV E21D 4 8 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. These results suggest that the combination of the 19I/E21D/A22V mutations may emerge and lead to high-level resistance to multiple PIs. 2006 Journal of virology Abstract HIV A22V;E21D 59;54 63;58 PI 131 134 16731952 Functional correlation between a novel amino acid insertion at codon 19 in the protease of human immunodeficiency virus type 1 and polymorphism in the p1/p6 Gag cleavage site in drug resistance and replication fitness. To characterize the role of these mutations in drug susceptibility and replication capacity, a chimeric HIV-1 strain containing the 19I/E21D/A22V mutations with the M46I/P63L/A71V/I84V/I93L and p1/p6 mutations was constructed. 2006 Journal of virology Abstract HIV A22V;A71V;E21D;I84V;I93L;M46I;P63L 141;175;136;180;185;165;170 145;179;140;184;189;169;174 Gag 197 199 16752922 Modulation of human immunodeficiency virus type 1 synergistic inhibition by reverse transcriptase mutations. Efavirenz displayed a 100 nM IC50 value against WT and the efavirenz-sensitive Y181C mutant, but the efavirenz-resistant mutants K103N and K103N/Y181C required a 6-fold increase in efavirenz concentration to achieve the same effect. 2006 Biochemistry Abstract HIV K103N;K103N;Y181C;Y181C 129;139;145;79 134;144;150;84 16752922 Modulation of human immunodeficiency virus type 1 synergistic inhibition by reverse transcriptase mutations. The IC50 value for inhibition by nevirapine against wild-type (WT) RT in our removal assay was 3 microM, but this concentration had no effect on removal by the nevirapine-resistant Y181C mutant. 2006 Biochemistry Abstract HIV Y181C 181 186 RT 67 69 16756753 Transduced Tat-alpha-synuclein protects against oxidative stress in vitro and in vivo. In this study, human wild type and mutant alpha-synuclein genes were fused with a gene fragment encoding the nine amino acid transactivator of transcription (Tat) protein transduction domain of HIV-1 in a bacterial expression vector to produce a genetic in-frame WT Tat-alpha-synuclein (wild type) and mutant Tat-alpha-synucleins (mutants; A30P and A53T), respectively, and we investigated the protective effects of wild type and mutant Tat-alpha-synucleins in vitro and in vivo. 2006 Journal of biochemistry and molecular biology Abstract HIV A30P;A53T 340;349 344;353 Tat;Tat;Tat;Tat 158;266;309;437 161;269;312;440 16759048 Three-year clinical outcomes of resistance genotyping and expert advice: extended follow-up of the Argenta trial. Independent predictors of new AIDS events/death were previous AIDS events, higher baseline viral load, less pronounced 3-month viral load drop and, in a separate model, baseline protease substitutions K20M/R and 184V. 2006 Antiviral therapy Abstract HIV K20M;K20R 201;201 207;207 PR 178 186 AIDS;AIDS 30;62 34;66 16759049 Evidence of differential selection of HIV-1 variants carrying drug-resistant mutations in seroconverters. Among RT mutations present both in PTs and SCs, M1841/V and T215F/Y had the lowest relative efficiency of transmission, whereas V1181, Y181C/I and K219E/Q showed the highest relative efficiency. 2006 Antiviral therapy Abstract HIV K219E;K219Q;T215F;T215Y;Y181C;Y181I 147;147;60;60;135;135 154;154;67;67;142;142 RT 6 8 16759049 Evidence of differential selection of HIV-1 variants carrying drug-resistant mutations in seroconverters. Among the mutations not detected in viruses from SCs, the RT E44D, V1081, Q151M and Y188C/H/L, and the protease D30N, G48V and V82A/F/S/T substitutions appeared to be negatively selected. 2006 Antiviral therapy Abstract HIV D30N;E44D;G48V;Q151M;V82A;V82F;V82S;V82T;Y188C;Y188H;Y188L 112;61;118;74;127;127;127;127;84;84;84 116;65;122;79;137;137;137;137;93;93;93 PR;RT 103;58 111;60 16759049 Evidence of differential selection of HIV-1 variants carrying drug-resistant mutations in seroconverters. Of the three major protease mutations that could be evaluated by this approach, M46l/L had a lower rate of transmission than 184V and L90M. 2006 Antiviral therapy Abstract HIV L90M 134 138 PR 19 27 16759055 In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine. The anti-HIV activity of the combination was studied in the human T leukaemic MT-2 cell line against wild-type or mutant virus (K65R and M184V) and in PBMCs against wild-type virus. 2006 Antiviral therapy Abstract HIV K65R;M184V 128;137 133;142 16762582 Polymorphisms and resistance mutations in the protease and reverse transcriptase genes of HIV-1 F subtype Romanian strains. The most frequent mutation was M36I (29 of 29 strains), followed by L63T, K20R, and L10V. 2007 International journal of infectious diseases Abstract HIV K20R;L10V;L63T;M36I 74;84;68;31 78;88;72;35 16763489 A dual superinfection and recombination within HIV-1 subtype B 12 years after primoinfection. This result suggests a superinfection with 2 HIV-1 strains, one of which showed the T215Y + M184V resistance mutations. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;T215Y 92;84 97;89 16763521 HIV-1 reverse transcriptase mutants resistant to nonnucleoside reverse transcriptase inhibitors do not adversely affect DNA synthesis: pre-steady-state and steady-state kinetic studies. In this study, we evaluated the polymerase function of 3 clinically occurring NNRTI-resistant RTs (K103N, P236L, and V106A) in greater detail, under both pre-steady-state and steady-state conditions. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;P236L;V106A 99;106;117 104;111;122 Pol;NNRTI;RT 32;78;94 42;83;97 16765636 Natural polymorphisms in the protease gene modulate the replicative capacity of non-B HIV-1 variants in the absence of drug pressure. All but one drug-naive individual carrying non-B viruses were fully susceptibility to all tested PI, suggesting that additional substitutions within the PR might compensate the reduced PI susceptibility caused by K20I and/or M36I. 2006 Journal of clinical virology Abstract HIV K20I;M36I 213;225 217;229 PI;PI;PR 97;185;153 99;187;155 16765636 Natural polymorphisms in the protease gene modulate the replicative capacity of non-B HIV-1 variants in the absence of drug pressure. OBJECTIVE: To evaluate the effect of two natural protease (PR) polymorphisms, K20I and M36I, which are frequently found in non-B subtypes, on the virus replicative capacity in the presence and absence of protease inhibitors (PI). 2006 Journal of clinical virology Abstract HIV K20I;M36I 78;87 82;91 PR;PR;PI;PR 49;204;225;59 57;212;227;61 16765636 Natural polymorphisms in the protease gene modulate the replicative capacity of non-B HIV-1 variants in the absence of drug pressure. RESULTS: In the absence of drug, the M36I clone replicated more rapidly than wt (wild type) or the double mutant K20I/M36I. 2006 Journal of clinical virology Abstract HIV K20I;M36I;M36I 113;37;118 117;41;122 16765636 Natural polymorphisms in the protease gene modulate the replicative capacity of non-B HIV-1 variants in the absence of drug pressure. STUDY DESIGN: Infectious HIV-1 clones carrying K20I, M36I or K20I/M36I were designed. 2006 Journal of clinical virology Abstract HIV K20I;K20I;M36I;M36I 47;61;66;53 51;65;70;57 16766190 QSAR for non-nucleoside inhibitors of HIV-1 reverse transcriptase. The optimal models found include up to seven parameters: R = 0.7991, R(l-20%-o) = 0.7233 for the case of wild-type, and R = 0.9261, R(l-5%-o) = 0.8802 for the K-103N mutation. 2006 Bioorganic & medicinal chemistry Abstract HIV K103N 159 165 16771502 Computational simulations of HIV-1 proteases--multi-drug resistance due to nonactive site mutation L90M. Exceptionally, some other mutations such as L90M cause drug resistance, although these appear at nonactive sites. 2006 Journal of the American Chemical Society Abstract HIV L90M 44 48 16771502 Computational simulations of HIV-1 proteases--multi-drug resistance due to nonactive site mutation L90M. In this study, we carried out computational simulations of L90M PR in complex with each of three kinds of inhibitors and one typical substrate, and we clarified the mechanism of resistance. 2006 Journal of the American Chemical Society Abstract HIV L90M 59 63 PR 64 66 16771502 Computational simulations of HIV-1 proteases--multi-drug resistance due to nonactive site mutation L90M. The difference in levels of resistance to the three inhibitors has been explained from energetic and structural viewpoints, which provides the suggestion for promising drugs keeping its efficacy even for the L90M mutant. 2006 Journal of the American Chemical Society Abstract HIV L90M 208 212 16771502 Computational simulations of HIV-1 proteases--multi-drug resistance due to nonactive site mutation L90M. The L90M mutation causes changes in interaction between the side chain atoms of the 90th residue and the main chain atoms of the 25th residue, and a slight dislocation of the 25th residue causes rotation of the side chain at the 84th residue. 2006 Journal of the American Chemical Society Abstract HIV L90M 4 8 16772295 Inhibition of early steps of HIV-1 replication by SNF5/Ini1. K71R substitution stimulates viral replication and results in higher infectious titers. 2006 The Journal of biological chemistry Abstract HIV K71R 0 4 16772295 Inhibition of early steps of HIV-1 replication by SNF5/Ini1. On the contrary, IN K71R retained in vitro integrase activity. 2006 The Journal of biological chemistry Abstract HIV K71R 20 24 IN;IN 43;17 52;19 16772295 Inhibition of early steps of HIV-1 replication by SNF5/Ini1. The E69G substitution completely abolished integrase catalytic activity, leading to a replication-defective virus. 2006 The Journal of biological chemistry Abstract HIV E69G 4 8 IN 43 52 16772295 Inhibition of early steps of HIV-1 replication by SNF5/Ini1. Two different mutants of interaction, IN E69G and IN K71R, were impaired for SNF5/Ini1 interaction. 2006 The Journal of biological chemistry Abstract HIV E69G;K71R 41;53 45;57 IN;IN 38;50 40;52 16773026 Linking HIV and antiretroviral drug resistance surveillance in Peru: a model for a third-generation HIV sentinel surveillance. The most frequently observed mutations in treatment-naive, chronically infected persons from Lima were M184V (1.7%), D30N (1.3%), L90M (1.3%), and L10I (1.3%). 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D30N;L10I;L90M;M184V 117;147;130;103 121;151;134;108 16773027 Update on primary HIV-1 resistance in Argentina: emergence of mutations conferring high-level resistance to nonnucleoside reverse transcriptase inhibitors in drug-naive patients. On reverse transcriptase, major resistance-related mutations were found in 4 of 52 (7.7%) patients from different health centers: M41L (subtype B) and K103N+/-P225H (1 RecBF and 2 subtype B). 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;M41L;P225H 151;130;159 156;134;164 RT 3 24 16773027 Update on primary HIV-1 resistance in Argentina: emergence of mutations conferring high-level resistance to nonnucleoside reverse transcriptase inhibitors in drug-naive patients. The substitution L89M, recently suggested as a resistance-related mutation in some subtype F viruses, was observed in 1 RecBF. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L89M 17 21 16773030 Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;K103N;K103N 49;191;17 54;196;22 16773030 Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 54 59 16773030 Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 25 30 16773030 Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 87 92 16773030 Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. K103N was rarely detected in pre-NVP samples. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 0 5 16773030 Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. RESULTS: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P < 0.0001). 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 48 53 16781756 The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. An additional mutation in reverse transcriptase (RT), G490E, was found to facilitate the forced use of tRNA(Lys1,2) as the primer. 2006 Virology Abstract HIV G490E 54 59 RT;RT 26;49 47;51 16781756 The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. Analysis of the replication of viruses with the U5 and PBS complementary to tRNA(Trp) with or without the G490E mutation revealed no significant differences with respect to infectivity and viral growth in SupT1 or peripheral blood mononuclear cells (PBMC). 2006 Virology Abstract HIV G490E 106 111 16781756 The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. In addition, the presence of the G490E mutation did not influence the capacity of this virus to revert to utilize tRNA(Met) as the primer for initiation of reverse transcription. 2006 Virology Abstract HIV G490E 33 38 RT 156 177 16781756 The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. In the current study, we have investigated the impact of the G490E mutation in RT on the selection and use of alternative primers by HIV-1. 2006 Virology Abstract HIV G490E 61 66 RT 79 81 16781756 The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. The G490E RT mutation in this virus did not impact on the virus infectivity or growth in SupT1 or PBMC. 2006 Virology Abstract HIV G490E 4 9 RT 10 12 16781756 The G490E mutation in reverse transcriptase does not impact tRNA primer selection by HIV-1 with altered PBS and A-loop. We did not find a significant fitness advantage to viruses in which the A-loop and PBS were made complementary to tRNA(Lys1,2) that also contained the G490E mutation in RT. 2006 Virology Abstract HIV G490E 151 156 RT 169 171 16784458 Optimization and computational evaluation of a series of potential active site inhibitors of the V82F/I84V drug-resistant mutant of HIV-1 protease: an application of the relaxed complex method of structure-based drug design. The compounds were evaluated by docking them against 700 different conformations of the V82F/I84V mutant. 2006 Chemical biology & drug design Abstract HIV I84V;V82F 93;88 97;92 16784458 Optimization and computational evaluation of a series of potential active site inhibitors of the V82F/I84V drug-resistant mutant of HIV-1 protease: an application of the relaxed complex method of structure-based drug design. The control cases used AutoDock3.0.5 to dock a fully flexible version of the prospective drug JE-2147 (aka SM-319777 or KNI-764) to large ensembles of conformations extracted from conventional, all atom, explicitly solvated molecular dynamic simulations of the wild type, and the V82F/I84V drug-resistant mutant of HIV-1 protease. 2006 Chemical biology & drug design Abstract HIV I84V;V82F 285;280 289;284 PR 321 329 16784767 Human immunodeficiency virus type 1 nucleocapsid zinc-finger mutations cause defects in reverse transcription and integration. Over a 72-h time-course of infection, the quantities of viral DNA (vDNA) observed with viruses containing either the nucleocapsid His23Cys or His44Cys mutations were significantly lower than those observed in infections with virus containing wild-type NC. 2006 Virology Abstract HIV H23C;H44C 130;142 138;150 NC 252 254 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The DNA binding properties and non-specific nuclease activity of the I267A derivatives suggest that the C-terminal domain of IN normally plays an important role in aligning the viral DNA end for proper processing. 2006 Retrovirology Abstract HIV I267A 69 74 IN 125 127 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Two of these derivatives, IN (I276A) and IN (I267A/I268A), exhibited both increased DNA binding affinity and uncharacteristic dissociation kinetics; these proteins also exhibited non-specific nuclease activity. 2006 Retrovirology Abstract HIV I267A;I268A;I276A 45;51;30 50;56;35 IN;IN 26;41 28;43 16791013 Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa. Fourteen had M184V [10 with one to four additional nucleoside analogue mutations (NAMs)]; one had three NAMs only; and the remaining three had K65R. 2006 AIDS (London, England) Abstract HIV K65R;M184V 143;13 147;18 16791013 Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa. In this population, who were infected with HIV-1 subtypes A, C or D, M184V with or without NAMs was the most common route to resistance, whereas K65R was identified less often. 2006 AIDS (London, England) Abstract HIV K65R;M184V 145;69 149;74 16791013 Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa. One participant with M184V had major non-nucleoside reverse transcriptase inhibitor-associated mutations, despite no disclosed treatment with this class. 2006 AIDS (London, England) Abstract HIV M184V 21 26 NNRTI 37 73 16794810 Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations. In this paper, we report the first computational study of the clinically relevant E35D mutation of HIV-1 protease in its unbound conformation and complexed with the clinical inhibitor amprenavir and a sample substrate (Thr-Ile-Met-Met-Gln-Arg). 2007 Journal of molecular modeling Abstract HIV E35D 82 86 PR 105 113 16794810 Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations. One possible explanation for the emergence of this mutation, despite its unfavorable effect on substrate affinity, might be the role of E35D as an escape mutation, which favors escape from the immune system in addition to conferring drug resistance. 2007 Journal of molecular modeling Abstract HIV E35D 136 140 16794810 Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations. Our data, collected from 10 ns molecular-dynamics simulations, show that the E35D mutation results in an increased flexibility of the flaps, thereby affecting the conformational equilibrium between the closed and semi-open conformations of the free protease. 2007 Journal of molecular modeling Abstract HIV E35D 77 81 PR 249 257 16794810 Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations. The E35D mutation also causes a significant reduction of the calculated binding free energies both for substrate and amprenavir, thus giving a plausible explanation for its ability to increase the level of resistance. 2007 Journal of molecular modeling Abstract HIV E35D 4 8 16796535 High HIV type 1 subtype diversity and few drug resistance mutations among seropositive people detected during the 2005 second generation HIV surveillance in Madagascar. According to the ANRS September 2005 DRM list and algorithm, no DRM was detected in the reverse transcriptase and only one strain bore three major DRM in the protease M46I, I84V, and L90M leading to resistance to indinavir, saquinavir, nelfinavir, atazanavir/ritonavir, and possibly lopinavir. 2006 AIDS research and human retroviruses Abstract HIV I84V;L90M;M46I 173;183;167 177;187;171 RT;PR 88;158 109;166 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. Efavirenz resistance during HIV-1 treatment failure is usually associated with the reverse transcriptase mutation K103N. 2006 Virology Abstract HIV K103N 114 119 RT 83 104 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. In the absence of efavirenz, the fitness of V108I was indistinguishable from wild type. 2006 Virology Abstract HIV V108I 44 49 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. In the presence of efavirenz, L100I was less fit than K103N, and K103N + L100I was more fit than K103N + V108I. 2006 Virology Abstract HIV K103N;K103N;K103N;L100I;L100I;V108I 54;65;97;30;73;105 59;70;102;35;78;110 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. K103N + L100I had a greater reduction in fitness and was less fit than K103N + V108I and K103N + P225H. 2006 Virology Abstract HIV K103N;K103N;L100I;P225H;V108I;K103N 71;89;8;97;79;0 76;94;13;102;84;5 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. K103N + L100I is the most drug-resistant of the double mutants but is the least common clinically. 2006 Virology Abstract HIV L100I;K103N 8;0 13;5 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. K103N, L100I, and P225H were minimally, but consistently, less fit than wild type. 2006 Virology Abstract HIV L100I;P225H;K103N 7;18;0 12;23;5 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. L100I, V108I, or P225H can emerge after K103N and increase its level of efavirenz resistance. 2006 Virology Abstract HIV K103N;P225H;V108I;L100I 40;17;7;0 45;22;12;5 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. The fitness defect of K103N + L100I relative to K103N was completely compensated for by the addition of the nucleoside resistance mutation L74V. 2006 Virology Abstract HIV K103N;K103N;L100I;L74V 22;48;30;139 27;53;35;143 16797050 Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. We measured fitness of each secondary mutant introduced into HIV(NL4-3), alone and in combination with K103N, using growth competition assays in H9 cells. 2006 Virology Abstract HIV K103N 103 108 16798669 Simian immunodeficiency virus envelope compartmentalizes in brain regions independent of neuropathology. Furthermore, gp160s with the mutation G383E were able to mediate cell-to-cell fusion in a CD4-independent manner and were more susceptible to fusion inhibition by pooled plasma from infected macaques. 2006 Journal of neurovirology Abstract HIV G383E 38 43 gp160 13 19 16799151 Effect of mutations on the dimer stability and the pH optimum of the human foamy virus protease. Specificity constant of most mutants was lower, but the value of Q8R-T28D double mutant enzyme was higher than that of the wild-type HFV PR. 2006 Protein engineering, design & selection Abstract HIV Q8R;T28D 65;69 68;73 PR 137 139 16799151 Effect of mutations on the dimer stability and the pH optimum of the human foamy virus protease. To explore the role of residues being close to the catalytic aspartates in the higher pH optimum and in the lower dimer stability of human foamy virus (HFV) protease (PR) in comparison with human immunodeficiency virus type 1 (HIV-1) protease, single (Q8R, H22L, S25T, T28D) and double (Q8R-T28D, H22L-T28D) mutants were created based on sequence alignments and on the molecular model of HFV PR. 2006 Protein engineering, design & selection Abstract HIV H22L;H22L;Q8R;Q8R;S25T;T28D;T28D;T28D 257;297;252;287;263;269;291;302 261;301;255;290;267;273;295;306 PR;PR;PR;PR 157;234;167;392 165;242;169;394 16801444 Risk factors for selection of the L74I reverse transcriptase mutation in human immunodeficiency virus type 1-infected patients. L74I was strongly associated with T215F, K70R, and V75M/S/T/A mutations and increased with the number of thymidine analog mutations. 2006 Antimicrobial agents and chemotherapy Abstract HIV K70R;T215F;V75A;V75M;V75S;V75T;L74I 41;34;51;51;51;51;0 45;39;61;61;61;61;4 16801444 Risk factors for selection of the L74I reverse transcriptase mutation in human immunodeficiency virus type 1-infected patients. The L74I mutation was carried by 7% of viruses. 2006 Antimicrobial agents and chemotherapy Abstract HIV L74I 4 8 16806925 Tri-substituted triazoles as potent non-nucleoside inhibitors of the HIV-1 reverse transcriptase. Several of these compounds exhibited potent antiviral activities against efavirenz- and nevirapine-resistant viruses, containing K103N and/or Y181C mutations or Y188L mutation. 2006 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C;Y188L 129;142;161 134;147;166 16809296 Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. Additionally, T80N decreased the conformational flexibility of the flap region, as observed by simulations of molecular dynamics. 2006 Journal of virology Abstract HIV T80N 14 18 16809296 Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. Both T80V and T80N had decreased the affinity for saquinavir. 2006 Journal of virology Abstract HIV T80N;T80V 14;5 18;9 16809296 Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. T80V significantly decreased the ability of the enzyme to cleave a peptide substrate but maintained infectivity, while T80N abolished both activity and viral infectivity. 2006 Journal of virology Abstract HIV T80N;T80V 119;0 123;4 16809296 Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. Three protease variants (T80V, T80N, and T80S) were examined for changes in structure, dynamics, enzymatic activity, affinity for protease inhibitors, and viral infectivity. 2006 Journal of virology Abstract HIV T80N;T80S;T80V 31;41;25 35;45;29 PR;PR 6;130 14;138 16809296 Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. While all three variants were structurally similar to the wild type, only T80S was functionally similar. 2006 Journal of virology Abstract HIV T80S 74 78 16809307 Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. By contrast, introduction of T215F into the D67N/K70R/K219Q background increased viral fitness in the presence of ZDV. 2006 Journal of virology Abstract HIV D67N;K219Q;K70R;T215F 44;54;49;29 48;59;53;34 16809307 Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. In addition, T215Y mutants showed greater infectivity than did wild-type HIV-1 over a range of ZDV concentrations, but T215F mutants had only a modest advantage over the wild-type virus. 2006 Journal of virology Abstract HIV T215F;T215Y 119;13 124;18 16809307 Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. The L210W mutation most often occurs with M41L and T215Y and rarely occurs with the T215F or TAM-2 mutation. 2006 Journal of virology Abstract HIV L210W;M41L;T215F;T215Y 4;42;84;51 9;46;89;56 16809307 Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. These results help explain why T215Y but not T215F usually emerges as the first major TAM, as well as the clustering of L210W with TAM-1 mutations and T215F with TAM-2 mutations. 2006 Journal of virology Abstract HIV L210W;T215F;T215F;T215Y 120;45;151;31 125;50;156;36 16809307 Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. Viruses carrying the 215Y mutation showed faster replication kinetics and greater relative fitness than did T215F mutants in the absence or presence of ZDV. 2006 Journal of virology Abstract HIV T215F 108 113 16809307 Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. Whereas introduction of L210W improved the relative fitness of an M41L/T215Y mutant in the presence of ZDV, introduction of this mutation into a D67N/K70R/K219Q background resulted in decreased relative fitness in the presence or absence of drug. 2006 Journal of virology Abstract HIV D67N;K219Q;K70R;L210W;M41L;T215Y 145;155;150;24;66;71 149;160;154;29;70;76 16809307 Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. Whereas T215Y occurs alone or with M41L and L210W (TAM-1 pattern), T215F rarely occurs with these mutations or by itself; it is found instead with D67N, K70R, and K219Q (TAM-2 pattern). 2006 Journal of virology Abstract HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 147;163;153;44;35;67;8 151;168;157;49;39;72;13 16809324 Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. Differently, D218E clustered with the NAM2 pathway (D67N+K70R+K219Q+T215F), and its presence in this cluster determined an increase in zidovudine resistance. 2006 Journal of virology Abstract HIV D218E;D67N;K219Q;K70R;T215F 13;52;62;57;68 18;56;67;61;73 16809324 Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. Finally, the association pattern of the F214L polymorphism revealed its propensity for the NAM2 pathway and its strong negative association with the NAM1 pathway. 2006 Journal of virology Abstract HIV F214L 40 45 16809324 Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. In contrast, three mutations (V35I, I50V, and R83K) negatively associated with NRTI treatment showed negative correlations with NRTI resistance mutations and were associated with increased susceptibility to specific NRTIs. 2006 Journal of virology Abstract HIV I50V;R83K;V35I 36;46;30 40;50;34 NRTI;NRTI;NRTI 79;128;216 83;132;221 16809324 Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. In particular, I50V negatively correlated with the lamivudine-selected mutation M184V and was associated with a decrease in M184V/lamivudine resistance, whereas R83K negatively correlated with both NAM1 and NAM2 clusters and was associated with a decrease in thymidine analogue resistance. 2006 Journal of virology Abstract HIV I50V;M184V;M184V;R83K 15;80;124;161 19;85;129;165 16809324 Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. In particular, T39A, K43E/Q, K122E, E203K, and H208Y clustered with the nucleoside analogue mutation 1 cluster (NAM1; M41L+L210W+T215Y). 2006 Journal of virology Abstract HIV E203K;H208Y;K122E;K43E;K43Q;L210W;M41L;T215Y;T39A 36;47;29;21;21;123;118;129;15 41;52;34;27;27;128;122;134;19 16809324 Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. Moreover, treatment failure in the presence of K43E, K122E, or H208Y was significantly associated with higher viremia and lower CD4 cell count. 2006 Journal of virology Abstract HIV H208Y;K122E;K43E 63;53;47 68;58;51 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. CONCLUSION: Tenofovir -based regimens will need to be carefully monitored in subtype C infections for the possible selection of K65R. 2006 AIDS (London, England) Abstract HIV K65R 128 132 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. In contrast, times to the appearance of M184V with lamivudine pressure (weeks 8-14) did not vary among subtypes. 2006 AIDS (London, England) Abstract HIV M184V 40 45 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. K65R appeared after 55 and 73 weeks in two CRF1_AE selections with tenofovir. 2006 AIDS (London, England) Abstract HIV K65R 0 4 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. Phenotypic assays determined the effects of the K65R substitution in reverse transcriptase (RT) on drug susceptibility. 2006 AIDS (London, England) Abstract HIV K65R 48 52 RT;RT 69;92 90;94 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. Selective didanosine pressure resulted in the appearance of M184V and L74V after 38 weeks in two of four subtype C selections. 2006 AIDS (London, England) Abstract HIV L74V;M184V 70;60 74;65 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. The K65R mutation (AAG-->AGG) arose with tenofovir by week 12 in four subtype C selections. 2006 AIDS (London, England) Abstract HIV K65R 4 8 16816549 HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. The K65R transitions in subtype C and other subtypes (AGG and AGA) conferred similar 6.5-10-fold resistance to tenofovir and five to 25-fold cross-resistance to each of abacavir, lamivudine, and didanosine, while not affecting zidovudine susceptibility. 2006 AIDS (London, England) Abstract HIV K65R 4 8 16816563 Presence of numerous stop codons in HIV-1 reverse transcriptase proviral DNA sequences from patients with virological response to HAART. Neither the M184I/V mutation detected in 12 patients nor stop codons at tryptophane positions detected in 13 patients were associated with virological failure. 2006 AIDS (London, England) Abstract HIV M184I;M184V 12;12 19;19 16825395 Blinded, multicenter comparison of methods to detect a drug-resistant mutant of human immunodeficiency virus type 1 at low frequency. We determined the abilities of 10 technologies to detect and quantify a common drug-resistant mutant of human immunodeficiency virus type 1 (lysine to asparagine at codon 103 of the reverse transcriptase) using a blinded test panel containing mutant-wild-type mixtures ranging from 0.01% to 100% mutant. 2006 Journal of clinical microbiology Abstract HIV K103N 141 175 RT 182 203 16841549 Temporal characterization of drug resistance associated mutations in HIV-1 protease and reverse transcriptase in patients failing antiretroviral therapy. From 1999 to 2003, resistance-mutations to drugs with high genetic-barrier significantly decreased (L90M/V82A/M46I/I54V/G73S/I84V/G48V for PIs; M41L/D67N/L210W/V1181 for NRTIs, p < 0.05), while mutations to drugs with low genetic-barrier increased (D30N in protease, M184V/K103N/V108I in reverse transcriptase, p < 0.05). 2006 The new microbiologica Abstract HIV L90M;D67N;G48V;G73S;I54V;I84V;K103N;L210W;M184V;M41L;M46I;V108I;V82A;D30N 100;149;130;120;115;125;273;154;267;144;110;279;105;249 104;153;134;124;119;129;278;159;272;148;114;284;109;254 RT;PR;NRTI;PI 288;257;170;139 309;265;175;142 16847406 Identification of alternative amino acid substitutions in drug-resistant variants of the HIV-1 reverse transcriptase. Phenotypic analysis indicated that drug-resistance properties of the alternative Y181V and L74I mutants are similar, but not identical, to that of the well-known Y181C and L74V mutations. 2006 AIDS (London, England) Abstract HIV L74I;L74V;Y181C;Y181V 91;172;162;81 95;176;167;86 16849040 Genetic characterization of human immunodeficiency virus type 1 from Beira, Mozambique. Although an unexpectedly high rate (11.6%) of reverse transcriptase key mutations (V75A, K103N, Y181C, M184I, or P236L) was detected in the sequences analyzed, our data suggest the non-epidemic circulation of resistant viruses, and the absence of multi-class drug resistant viral strains. 2006 Microbes and infection Abstract HIV K103N;M184I;P236L;V75A;Y181C 89;103;113;83;96 94;108;118;87;101 RT 46 67 16849040 Genetic characterization of human immunodeficiency virus type 1 from Beira, Mozambique. Analysis of the predicted protease sequences enabled us to detect a single primary mutation (I84V, n=1) associated with resistance to protease inhibitors (PI), while secondary mutations were highly prevalent, some of them in combinations which may confer PI resistance. 2006 Microbes and infection Abstract HIV I84V 93 97 PR;PR;PI;PI 26;134;155;255 34;142;157;257 16851048 Resistant mechanism against nelfinavir of human immunodeficiency virus type 1 proteases. Among patients who failed in the inhibitor nelfinavir (NFV) treatment, D30N, N88D, and L90M mutations of HIV-1 protease are often observed. 2005 The journal of physical chemistry. B Abstract HIV D30N;L90M;N88D 71;87;77 75;91;81 PR 111 119 16851048 Resistant mechanism against nelfinavir of human immunodeficiency virus type 1 proteases. D30N mutation causes the disappearance of the hydrogen bond between the m-phenol group of NFV and the 30th residue. 2005 The journal of physical chemistry. B Abstract HIV D30N 0 4 16851048 Resistant mechanism against nelfinavir of human immunodeficiency virus type 1 proteases. Despite the serious clinical problem, it is not clear how these mutations, especially nonactive site mutations N88D and L90M, affect the affinity of NFV or why they cause the resistance to NFV. 2005 The journal of physical chemistry. B Abstract HIV L90M;N88D 120;111 124;115 16851048 Resistant mechanism against nelfinavir of human immunodeficiency virus type 1 proteases. In this study, we executed molecular dynamics simulations of the NFV-bound proteases in the wild-type and D30N, N88D, D30N/N88D, and L90M mutants. 2005 The journal of physical chemistry. B Abstract HIV D30N;D30N;L90M;N88D;N88D 106;118;133;112;123 110;122;137;116;127 PR 75 84 16851048 Resistant mechanism against nelfinavir of human immunodeficiency virus type 1 proteases. L90M mutation dramatically changes the conformation at the flap region and leads to an unfavorable distortion of the binding pocket of the protease, although 90M is largely far apart from the flap region. 2005 The journal of physical chemistry. B Abstract HIV L90M 0 4 PR 139 147 16851048 Resistant mechanism against nelfinavir of human immunodeficiency virus type 1 proteases. N88D mutation alters the active site conformation slightly and induces a favorable hydrophobic contact. 2005 The journal of physical chemistry. B Abstract HIV N88D 0 4 16856615 Virological responses to atazanavir-ritonavir-based regimens: resistance-substitutions score and pharmacokinetic parameters (Reyaphar study). The Reyaphar score included 12 baseline protease substitutions from the International AIDS Society USA list that were associated with poorer VR: L10I/F/R/V, K20I/M/R, L241, M461/L, 154L/M/T/V, L63P, A71I/L/V/T, G73A/C/F/T, V771, V82A/F/S/T, 184V, L90M and the polymorphism substitution Q58E. 2006 Antiviral therapy Abstract HIV A71I;A71L;A71T;A71V;G73A;G73C;G73F;G73T;K20I;K20M;K20R;L10F;L10I;L10R;L10V;L63P;L90M;Q58E;V82A;V82F;V82S;V82T 199;199;199;199;211;211;211;211;157;157;157;145;145;145;145;193;247;286;229;229;229;229 209;209;209;209;221;221;221;221;165;165;165;155;155;155;155;197;251;290;239;239;239;239 PR 40 48 AIDS 86 90 16870771 Novel nonnucleoside inhibitors that select nucleoside inhibitor resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. Although the M184V mutation appears to be the initial mutation to establish resistance, this mutation alone confers only a two- to fourfold decrease in susceptibility to VRX-329747 and VRX-413638. 2006 Antimicrobial agents and chemotherapy Abstract HIV M184V 13 18 16870771 Novel nonnucleoside inhibitors that select nucleoside inhibitor resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. Moreover, while VRX-329747-selected viruses are resistant to lamivudine and emtricitabine due to the M184V mutation, they remain susceptible to zidovudine, stavudine, dideoxyinosine, abacavir, tenofovir, and efavirenz. 2006 Antimicrobial agents and chemotherapy Abstract HIV M184V 101 106 16870771 Novel nonnucleoside inhibitors that select nucleoside inhibitor resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. Rather, four mutations (M41L, A62T/V, V118I, and M184V) known to cause resistance to NRTIs and two additional novel mutations (S68N and G112S) adjacent to the catalytic site of the enzyme were selected. 2006 Antimicrobial agents and chemotherapy Abstract HIV A62T;A62V;G112S;M184V;M41L;S68N;V118I 30;30;136;49;24;127;38 36;36;141;54;28;132;43 NRTI 85 90 16870786 Alkoxyalkyl esters of (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine are potent inhibitors of the replication of wild-type and drug-resistant human immunodeficiency virus type 1 in vitro. Resistance to HDP-(S)-HPMPA and ODE-(S)-HPMPA was noted for a mutant with mutation K65R. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65R 83 87 16870786 Alkoxyalkyl esters of (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine are potent inhibitors of the replication of wild-type and drug-resistant human immunodeficiency virus type 1 in vitro. We synthesized several alkoxyalkyl esters of (S)-HPMPA and now report that hexadecyloxypropyl-(S)-HPMPA [HDP-(S)-HPMPA] and octadecyloxyethyl-(S)-HPMPA [ODE-(S)-HPMPA]had 50% effective concentrations of 0.4 to 7.0 nanomolar and were nearly fully active against HIV variants having reverse transcriptase mutations M184V and K103N and against a zidovudine-resistant variant with mutations D67N, K70R, T215Y, and K219Q. 2006 Antimicrobial agents and chemotherapy Abstract HIV D67N;K103N;K219Q;K70R;M184V;T215Y 387;323;410;393;313;399 391;328;415;397;318;404 RT 281 302 16873273 Compensatory substitutions restore normal core assembly in simian immunodeficiency virus isolates with Gag epitope cytotoxic T-lymphocyte escape mutations. However, these defects were restored by the introduction of upstream I26V and/or downstream I71V substitutions in CA. 2006 Journal of virology Abstract HIV I26V;I71V 69;92 73;96 Capsid 114 116 16873273 Compensatory substitutions restore normal core assembly in simian immunodeficiency virus isolates with Gag epitope cytotoxic T-lymphocyte escape mutations. We show that a residue 2 mutation in the immunodominant p11C, C-M epitope (T47I) of SIV/SHIV not only decreased CA protein expression and viral replication, but it also blocked CA assembly in vitro and virion core condensation in vivo. 2006 Journal of virology Abstract HIV T47I 75 79 Capsid;Capsid 112;177 114;179 16875739 Association of Gag cleavage sites to protease mutations and to virological response in HIV-1 treated patients. On the other hand, the S373P mutation had a negative impact on the virological response that remained statistically significant in a multivariate analysis after adjustment on the number of PI resistance mutations. 2007 The Journal of infection Abstract HIV S373P 23 28 PI 189 191 16875739 Association of Gag cleavage sites to protease mutations and to virological response in HIV-1 treated patients. Two patterns of mutations in the protease were identified: (M46I/L, I54V, V82A/T/F) was associated to the A431V and (K20I/R/M, L89M/I) to the S373Q and L449P. 2007 The Journal of infection Abstract HIV A431V;I54V;K20I;K20M;K20R;L449P;L89I;L89M;M46I;M46L;S373Q;V82A;V82F;V82T 106;68;117;117;117;152;127;127;60;60;142;74;74;74 111;72;125;125;125;157;133;133;66;66;147;82;82;82 PR 33 41 16885776 Rapid emergence of enfuvirtide resistance in HIV-1-infected patients: results of a clonal analysis. Mutations at codons 36 (G36E, G36D, or G36S) and 38 (V38A, V38G, or V38M) were the most commonly detected resistance mutations at week 2. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G36D;G36E;G36S;V38A;V38G;V38M 30;24;39;53;59;68 34;28;43;57;63;72 16885776 Rapid emergence of enfuvirtide resistance in HIV-1-infected patients: results of a clonal analysis. Mutations at codons 40 (Q40H) and 43 (N43D) were more prevalent at week 4 than at week 2 and seemed to emerge more slowly than mutations at codons 36 and 38. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N43D;Q40H 38;24 42;28 16885781 Emergence of antiretroviral therapy resistance-associated primary mutations among drug-naive HIV-1-infected individuals in rural western Cameroon. Protease inhibitor-associated primary resistance mutations were found in 4 (7.4%) cases: M46L with full clones in 1 case, and M46I, M46L, and V82A as minor populations in 1 case each. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M46I;M46L;M46L;V82A 126;89;132;142 130;93;136;146 PR 0 8 16885781 Emergence of antiretroviral therapy resistance-associated primary mutations among drug-naive HIV-1-infected individuals in rural western Cameroon. Reverse transcriptase inhibitor-associated primary resistance mutations were found in 5 (9.8%) samples: Y188C in 2 cases, and L100I, M184V, and V75I in 1 case each, although all of these mutations were found as minor populations. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L100I;M184V;V75I;Y188C 126;133;144;104 131;138;148;109 RT 0 21 16891628 Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment. CONCLUSIONS: Specific enfuvirtide resistance mutations (V38A/E) are associated with a sustained CD4 increase, without remarkable effects upon viraemia. 2006 The Journal of antimicrobial chemotherapy Abstract HIV V38A;V38E 56;56 62;62 16891628 Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment. In contrast, Q40H + L45M (present in six enfuvirtide-treated patients at week 36) correlated with CD4 loss from baseline to week 36 (P = 0.02), without significant correlation with viraemia. 2006 The Journal of antimicrobial chemotherapy Abstract HIV L45M;Q40H 20;13 24;17 16891628 Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment. Mutation N126K (observed in six enfuvirtide-treated patients, never found at baseline) abrogates the fourth gp41 glycosylation site and correlates with a 2.1-fold CD4 increase at week 24. 2006 The Journal of antimicrobial chemotherapy Abstract HIV N126K 9 14 gp41 108 112 16891628 Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment. The presence of V38A/E was significantly associated with a 4.5-fold CD4 increase from baseline to week 24 and with a 6-fold increase at week 36 (P = 0.004 and 0.02 compared without V38A/E, respectively), without significant correlation with viraemia. 2006 The Journal of antimicrobial chemotherapy Abstract HIV V38A;V38A;V38E;V38E 16;181;16;181 22;187;22;187 16891628 Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment. V38A/E were the most represented mutations at all time-points. 2006 The Journal of antimicrobial chemotherapy Abstract HIV V38A;V38E 0;0 6;6 16897578 Towards discovering dual functional inhibitors against both wild type and K103N mutant HIV-1 reverse transcriptases: molecular docking and QSAR studies on 4,1-benzoxazepinone analogues. Furthermore, CoMFA models were found to be well matched with the binding sites of both WT and K103N RTs. 2006 Journal of computer-aided molecular design Abstract HIV K103N 94 99 RT 100 103 16897578 Towards discovering dual functional inhibitors against both wild type and K103N mutant HIV-1 reverse transcriptases: molecular docking and QSAR studies on 4,1-benzoxazepinone analogues. To find useful information for discovering dual functional inhibitors against both wild type (WT) and K103N mutant reverse transcriptases (RTs) of HIV-1, molecular docking and 3D-QSAR approaches were applied to a set of twenty-five 4,1-benzoxazepinone analogues of efavirenz (SUSTIVA), some of them are active against the two RTs. 2006 Journal of computer-aided molecular design Abstract HIV K103N 102 107 RT;RT;RT 115;139;326 137;142;329 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. K65R and multiple TAMs were rarely detected (<0.1%) in the same plasma sample. 2006 The Journal of infectious diseases Abstract HIV K65R 0 4 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. K65R was never found on the same genome with T215F/Y and >or=2 other TAMs, except in the presence of the Q151M multiple nucleoside reverse-transcriptase inhibitor (NRTI)--resistance complex. 2006 The Journal of infectious diseases Abstract HIV Q151M;T215F;T215Y;K65R 105;45;45;0 110;52;52;4 NRTI;NRTI 120;164 152;168 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. Prior virologic and biochemical studies have shown phenotypic antagonism between K65R and multiple thymidine-analogue mutations (TAMs) in site-directed mutants tested in vitro. 2006 The Journal of infectious diseases Abstract HIV K65R 81 85 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. Samples with both K65R and >or=3 TAMs (n=21) were further analyzed by use of single-genome sequencing. 2006 The Journal of infectious diseases Abstract HIV K65R 18 22 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. These results indicate that antagonism between the K65R and T215Y/F pathways of NRTI resistance occurs at the genomic level. 2006 The Journal of infectious diseases Abstract HIV K65R;T215F;T215Y 51;60;60 55;67;67 NRTI 80 84 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. We hypothesized, on the basis of this observed antagonism, that K65R and T215Y/F with multiple TAMs would not be selected on the same human immunodeficiency virus type 1 genome in vivo. 2006 The Journal of infectious diseases Abstract HIV K65R;T215F;T215Y 64;73;73 68;80;80 16897664 Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level. We searched a large database of patient genotypes (n=59,262) for the frequency of K65R in combination with >or=3 TAMs as determined by standard population sequencing. 2006 The Journal of infectious diseases Abstract HIV K65R 82 86 16910833 Subtype-specific patterns in HIV Type 1 reverse transcriptase and protease in Oyo State, Nigeria: implications for drug resistance and host response. Six of 35 (17%) individuals harbored primary mutations for RT inhibitors, including M41L, V118I, Y188H, P236L, and Y318F, and curiously three of the six were infected with CRF06_cpx. 2006 AIDS research and human retroviruses Abstract HIV M41L;P236L;V118I;Y188H;Y318F 84;104;90;97;115 88;109;95;102;120 RT 59 61 16911530 Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138. Both RT(Glu138Lys) and RT(Lys101Glu) have remarkably similar protein conformations to wild-type RT, except for significant movement of the mutated side-chains away from the NNRTI pocket induced by charge inversion. 2006 The FEBS journal Abstract HIV E138K;K101E;R101E;R138K;T101E;T138K 8;26;26;8;26;8 17;35;35;17;35;17 NNRTI;RT;RT;RT 173;5;23;96 178;7;25;98 16911530 Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138. However, nevirapine contacts Lys101 and Glu138 only indirectly, via water molecules, thus the structural basis of drug resistance induced by Lys101Glu is unclear. 2006 The FEBS journal Abstract HIV K101E 141 150 16911530 Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138. However, the reduction in hydrogen bonds in the drug-water-side-chain network resulting from the mutated side-chain movement appears to be the most significant contribution to nevirapine resistance for RT(Lys101Glu). 2006 The FEBS journal Abstract HIV K101E;R101E;T101E 205;205;205 214;214;214 RT 202 204 16911530 Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138. Lys101Glu is a drug resistance mutation in reverse transcriptase clinically observed in HIV-1 from infected patients treated with the non-nucleoside inhibitor (NNRTI) drugs nevirapine and efavirenz. 2006 The FEBS journal Abstract HIV K101E 0 9 RT;NNRTI 43;160 64;165 16911530 Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138. RT(Lys101Glu) is thus a distinctive NNRTI resistance mutant in that it can give rise to both direct and indirect mechanisms of drug resistance, which are inhibitor-dependent. 2006 The FEBS journal Abstract HIV K101E;R101E;T101E 3;3;3 12;12;12 NNRTI;RT 36;0 41;2 16911530 Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138. The movement of Glu101 away from the NNRTI pocket can also explain the resistance of RT(Lys101Glu) to efavirenz but in this case is due to a loss of side-chain contacts with the drug. 2006 The FEBS journal Abstract HIV K101E;R101E;T101E 88;88;88 97;97;97 NNRTI;RT 37;85 42;87 16911530 Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138. We have determined crystal structures of RT(Glu138Lys) and RT(Lys101Glu) in complexes with nevirapine to 2.5 A, allowing the determination of water structure within the NNRTI-binding pocket, essential for an understanding of nevirapine binding. 2006 The FEBS journal Abstract HIV E138K;K101E;R101E;R138K;T101E;T138K 44;62;62;44;62;44 53;71;71;53;71;53 NNRTI;RT;RT 169;41;59 174;43;61 16920659 Computer-aided molecular design of highly potent HIV-1 RT inhibitors: 3D QSAR and molecular docking studies of efavirenz derivatives. Ligand- and structure-based design approaches have been applied to an extended series of 74 efavirenz compounds effectively inhibiting wild type (WT) and mutant type (K103N) HIV-1 reverse transcriptase (RT). 2006 SAR and QSAR in environmental research Abstract HIV K103N 167 172 RT;RT 180;203 201;205 16920659 Computer-aided molecular design of highly potent HIV-1 RT inhibitors: 3D QSAR and molecular docking studies of efavirenz derivatives. Regarding WT and K103N inhibitions, CoMFA models with r2/cv = 0.651 and 0.678 and CoMSIA models with r2/cv = 0.662 and 0.743 were derived, respectively. 2006 SAR and QSAR in environmental research Abstract HIV K103N 17 22 16920659 Computer-aided molecular design of highly potent HIV-1 RT inhibitors: 3D QSAR and molecular docking studies of efavirenz derivatives. The interpretation obtained from the models highlights different structural requirements for inhibition of WT and K103N HIV-1 RT. 2006 SAR and QSAR in environmental research Abstract HIV K103N 114 119 RT 126 128 16920659 Computer-aided molecular design of highly potent HIV-1 RT inhibitors: 3D QSAR and molecular docking studies of efavirenz derivatives. To elucidate potential binding modes of efavirenz derivatives in the binding pocket of WT and K103N HIV-1 RT, structure-based approach based on computational docking studies of selected efavirenz compounds were performed by using GOLD and FlexX programs. 2006 SAR and QSAR in environmental research Abstract HIV K103N 94 99 RT 106 108 16920824 Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice. Also, both anchor-enhanced RT-WT (RT-2L9V) and RT-2L9V-M184V-specific CTLs recognized RT-M184V and displayed cross-reactivity to RT-WT. 2006 Journal of virology Abstract HIV M184V;M184V 55;89 60;94 RT;RT;RT;RT;RT 27;34;47;86;129 29;36;49;88;131 16920824 Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice. Here, we sought to determine whether a peptide vaccine could be developed using an epitope enhancement strategy that could induce a cytotoxic T-lymphocyte (CTL) response specific for an epitope containing the drug resistance mutation M184V to exert an opposing selective pressure. 2006 Journal of virology Abstract HIV M184V 234 239 16920824 Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice. High-grade resistance to the nucleoside reverse transcriptase (RT) inhibitor lamivudine (also known as 3TC) is associated with a substitution of valine for methionine at position 184 of RT. 2006 Journal of virology Abstract HIV M184V 145 182 NRTI;RT;RT 29;63;186 61;65;188 16920824 Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice. However, RT-M184V exhibited higher binding affinity for HLA-A2 than RT-WT. 2006 Journal of virology Abstract HIV M184V 12 17 RT;RT 9;68 11;70 16920824 Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice. Nevertheless, the CTL repertoire elicited by the epitope-enhanced RT-2L9V-M184V appeared more selective for the RT inhibitor-induced M184V mutation. 2006 Journal of virology Abstract HIV M184V;M184V 74;133 79;138 RT;RT 66;112 68;114 16920824 Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice. Peptide vaccines based on such strategies may be worth testing for their ability to exert selective pressure against drug-resistant strains and thus delay or prevent the development of HIV with the M184V resistance mutation. 2006 Journal of virology Abstract HIV M184V 198 203 16920824 Possible therapeutic vaccine strategy against human immunodeficiency virus escape from reverse transcriptase inhibitors studied in HLA-A2 transgenic mice. RT-WT-specific CTLs developed from HLA-A2 transgenic mice did not recognize the M184V mutation of RT-WT (RT-M184V). 2006 Journal of virology Abstract HIV M184V;M184V 80;108 85;113 RT;RT;RT 0;98;105 2;100;107 16925730 Resistance development over 144 weeks in treatment-naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903. In the d4T arm, a variety of NRTI mutations developed: K65R (n = 2), L74V (n = 2), V75M (n = 1), and T69A + Y115H (n = 1). 2006 HIV medicine Abstract HIV K65R;L74V;T69A;V75M;Y115H 55;69;101;83;108 59;73;105;87;113 NRTI 29 33 16925730 Resistance development over 144 weeks in treatment-naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903. K65R developed in eight TDF patients (2.7%); in seven of these eight patients, within 48 weeks. 2006 HIV medicine Abstract HIV K65R 0 4 16925730 Resistance development over 144 weeks in treatment-naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903. Resistance to EFV (K103N and others) or 3TC (M184V) developed most frequently (8.3% and 5.8%, respectively) and similarly in the two arms. 2006 HIV medicine Abstract HIV K103N;M184V 19;45 25;50 16926150 Reduced dNTP interaction of human immunodeficiency virus type 1 reverse transcriptase promotes strand transfer. To test this hypothesis, we employed two dNTP binding HIV-1 RT mutants, Q151N and V148I. 2006 The Journal of biological chemistry Abstract HIV Q151N;V148I 72;82 77;87 RT 60 62 16931138 Coexistence of the K65R/L74V and/or K65R/T215Y mutations on the same HIV-1 genome. Analysis of 73 clones (patient 1: 12 clones; patient 2: 27 clones; patient 3: 13 clones; patient 4: 21 clones) showed that 29 clones harboured K65R and L74V/I mutations. 2006 Journal of clinical virology Abstract HIV K65R;L74I;L74V 143;152;152 147;158;158 16931138 Coexistence of the K65R/L74V and/or K65R/T215Y mutations on the same HIV-1 genome. OBJECTIVE: To determine to which extent the mutations K65R, L74V/I and T215Y/F are linked to the same HIV-1 genome. 2006 Journal of clinical virology Abstract HIV K65R;L74I;L74V;T215F;T215Y 54;60;60;71;71 58;66;66;78;78 16931138 Coexistence of the K65R/L74V and/or K65R/T215Y mutations on the same HIV-1 genome. Twenty-three per cent of clones from the two bulk sequences harbouring K65K/R and T215T/Y genotypic mixtures contained K65R and T215Y on the same viral genome. 2006 Journal of clinical virology Abstract HIV K65K;K65R;K65R;T215T;T215Y;T215Y 71;71;119;82;82;128 77;77;123;89;89;133 16931582 Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). 2006 The Journal of molecular diagnostics Abstract HIV K103N;K103N 44;109 49;114 16931582 Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. 2006 The Journal of molecular diagnostics Abstract HIV K103N 44 49 16931582 Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. 2006 The Journal of molecular diagnostics Abstract HIV K103N 65 70 16931582 Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. 2006 The Journal of molecular diagnostics Abstract HIV K103N;K103N;K103N;K103N;K103N 17;52;91;129;170 22;57;96;134;175 16931582 Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. 2006 The Journal of molecular diagnostics Abstract HIV K103N 29 34 16931934 Antiretroviral resistance in viral isolates from HIV-1-transmitting mothers and their infants. The only NNRTI-associated mutation observed, K103N, was not transmitted, nor were the two major PI-associated mutations, L90M and V82I/V. 2006 AIDS (London, England) Abstract HIV K103N;L90M;V82I;V82V 45;121;130;130 50;125;136;136 NNRTI;PI 9;96 14;98 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. BACKGROUND: The K65R HIV-1 reverse transcriptase (RT) mutation is a multidrug resistance mutation which may be correlated with specific antiretroviral combinations and with the presence or absence of other RT resistance mutations. 2006 HIV medicine Abstract HIV K65R 16 20 RT;RT;RT 27;50;206 48;52;208 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. CONCLUSION: The K65R mutation may emerge preferentially in the absence of zidovudine and TAMs, suggesting the possibility of an antagonistic interaction between K65 and TAMs. 2006 HIV medicine Abstract HIV K65R 16 20 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. Genotypic patterns and treatment characteristics were examined at the time of detection of the K65R mutation. 2006 HIV medicine Abstract HIV K65R 95 99 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. K65R was associated with nucleoside RT inhibitor-based regimens in 22 patients, and with tenofovir disoproxil fumarate, lamivudine, didanosine and abacavir in 23, 17, 17 and eight patients, respectively. 2006 HIV medicine Abstract HIV K65R 0 4 RT 36 38 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. OBJECTIVES: The aims of this study were: (i) to determine the prevalence of the K65R mutation in a cohort of antiretroviral-treated patients; (ii) to study genotypic patterns and treatment characteristics in patients in whom the K65R mutation was present. 2006 HIV medicine Abstract HIV K65R;K65R 80;229 84;233 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. RESULTS: The prevalence of K65R was 1.9% (26 of 1404 patients). 2006 HIV medicine Abstract HIV K65R 27 31 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. The M184V and Q151M mutations were the most commonly co-selected substitutions. 2006 HIV medicine Abstract HIV M184V;Q151M 4;14 9;19 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. The prevalence of K65R was investigated for all patients. 2006 HIV medicine Abstract HIV K65R 18 22 16945074 HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation. Thymidine analogue mutations (TAMs) were rarely co-selected with K65R and inversely associated with K65R. 2006 HIV medicine Abstract HIV K65R;K65R 65;100 69;104 16951652 Diversity of HIV in rural Burkina Faso. Analysis of drug resistance-associated polymorphisms detected the nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations K103N/E and V118I in 1 individual each, suggesting transmission of drug-resistant viruses or prior use of antiretroviral drugs. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103E;K103N;V118I 141;141;153 148;148;158 NNRTI;NNRTI 66;113 101;118 16951652 Diversity of HIV in rural Burkina Faso. Resistance-associated polymorphisms (K20I and M36I) were prevalent in the complete protease (PR) region, but no primary drug resistance mutations were detected. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K20I;M36I 37;46 42;50 PR;PR 83;93 91;95 16956392 HIV-2 Protease resistance defined in yeast cells. CONCLUSION: This functional assay allowed us to show for the first time that the L90M substitution, present in a primary HIV-2 isolate, modifies the HIV-2 Protease susceptibility to Saquinavir but not Lopinavir. 2006 Retrovirology Abstract HIV L90M 81 85 PR 155 163 16956950 In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat). In contrast, mutations SP1-A3V and -A3T severely impaired virus replication and inhibited virion core condensation. 2006 Journal of virology Abstract HIV A3T;A3V 36;27 39;30 SP1 23 26 16956950 In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat). Numerous independent rounds of selection repeatedly identified six single-amino-acid substitutions that independently confer PA-457 resistance: three at or near the C terminus of CA (CA-H226Y, -L231F, and -L231M) and three at the first and third residues of SP1 (SP1-A1V, -A3T, and -A3V). 2006 Journal of virology Abstract HIV A1V;A3T;A3V;H226Y;L231F;L231M 267;273;283;186;194;206 270;276;286;191;199;211 SP1;SP1;Capsid;Capsid 258;263;179;183 261;266;181;185 16956950 In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat). The replication defect imposed by SP1-A3V was reversed by a second-site compensatory mutation in CA (CA-G225S). 2006 Journal of virology Abstract HIV G225S;A3V 104;38 109;41 SP1;Capsid;Capsid 34;97;101 37;99;103 16956950 In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat). We determined that mutations CA-H226Y, CA-L231F, CA-L231M, and SP1-A1V do not impose a significant replication defect on HIV-1 in culture. 2006 Journal of virology Abstract HIV A1V;H226Y;L231F;L231M 67;32;42;52 70;37;47;57 SP1;Capsid;Capsid;Capsid 63;29;39;49 66;31;41;51 16959283 Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a strict correlation between in vitro protein binding and HIV-1 fitness. His-tagged IN(A128Q), derived from a phenotypically wild-type virus, failed to pull-down LEDGF/p75, but IN(A128Q) was effectively recovered in a reciprocal GST pull-down assay. 2007 Virology Abstract HIV A128Q;A128Q 14;107 19;112 IN;IN 11;104 13;106 16959283 Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a strict correlation between in vitro protein binding and HIV-1 fitness. Under these conditions, IN(H171A), also derived from a phenotypically wild-type virus, interacted less efficiently than a previously described interaction-defective mutant, IN(Q168A). 2007 Virology Abstract HIV H171A;Q168A 27;176 32;181 IN;IN 24;173 26;175 16962136 Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114. We report the ultra-high 0.84 A resolution crystal structure of the TMC114 complex with PR containing the drug-resistant mutation V32I (PR(V32I)), and the 1.22 A resolution structure of a complex with PR(M46L). 2006 Journal of molecular biology Abstract HIV M46L;V32I;V32I 204;130;139 208;134;143 PR;PR;PR 88;136;201 90;138;203 16964825 HIV-1 drug-resistance mutations among newly diagnosed patients before scaling-up programmes in Burkina Faso and Cameroon. Eight of the 97 patients tested in Burkina Faso bore mutations conferring resistance to one drug class of ARV drugs: two to nucleoside reverse transcriptase inhibitors (NRTIs; M41L [n = 1], M41L+T69S [n = 1]), four to non-NRTIs (NNRTIs; V106A/V [n = 1] and V1081 [n = 3]) and two to protease inhibitors (PIs; L33F [n = 2]). 2006 Antiviral therapy Abstract HIV L33F;M41L;M41L;T69S;V106A;V106V 309;176;190;195;237;237 313;180;194;199;244;244 NRTI;NNRTI;PR;NNRTI;NRTI;PI 124;218;283;229;169;304 156;227;291;235;174;307 16964825 HIV-1 drug-resistance mutations among newly diagnosed patients before scaling-up programmes in Burkina Faso and Cameroon. In Cameroon, resistance mutations were identified in 8 of 102 patients: three to PIs (M461/L [n = 2], L33F [n = 1]), three to NRTIs (T69N/T [n = 1], M184V [n = 1], A62V [n = 1]) and two to NNRTIs (P236L [n = 1], V1081 [n = 1]). 2006 Antiviral therapy Abstract HIV A62V;L33F;M184V;P236L;T69N;T69T 164;102;149;197;133;133 168;106;154;203;140;140 NNRTI;NRTI;PI 189;126;81 195;131;84 16964832 Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted saquinavir. A third patient displayed a single new RT mutation (M184I). 2006 Antiviral therapy Abstract HIV M184I 52 57 RT 39 41 16964832 Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted saquinavir. No major PRO mutations were detected, but 2/8 displayed single new minor PRO substitutions (M36I, L10I) at VF that were known or suspected not to have been present at baseline; both these substitutions exist as natural polymorphisms. 2006 Antiviral therapy Abstract HIV L10I;M36I 98;92 102;96 16970402 HIV-1 protease mutations and inhibitor modifications monitored on a series of complexes. Structural basis for the effect of the A71V mutation on the active site. Comparison of eight structures exploring the binding of four similar inhibitors--SE, SQ (S-hydroxyethylamine isostere), OE (ethyleneamine), and QF34 (hydroxyethylene)--to wild-type and A71V/V82T/I84V HIV-1 protease elucidates the principles of altered interaction with changing conditions. 2006 Journal of medicinal chemistry Abstract HIV A71V;I84V;V82T 185;195;190 189;199;194 PR 206 214 16970402 HIV-1 protease mutations and inhibitor modifications monitored on a series of complexes. Structural basis for the effect of the A71V mutation on the active site. The A71V mutation, which is distant from the active site, causes changes in the structure of the enzyme detectable by the means of X-ray structure analysis, and a route of propagation of the effect toward the active site is proposed. 2006 Journal of medicinal chemistry Abstract HIV A71V 4 8 16970402 HIV-1 protease mutations and inhibitor modifications monitored on a series of complexes. Structural basis for the effect of the A71V mutation on the active site. Two new X-ray structures of an HIV-1 protease mutant (A71V, V82T, I84V) in complex with inhibitors SE and SQ, pseudotetrapeptide inhibitors with an acyclic S-hydroxyethylamine isostere, were determined. 2006 Journal of medicinal chemistry Abstract HIV A71V;I84V;V82T 54;66;60 58;70;64 PR 37 45 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. Here we report evidence for T cell activity against the drug resistant K103N region of viral reverse transcriptase in three HIV-1 infected patients exposed to NNRTI antiretroviral drugs. 2006 AIDS research and therapy Abstract HIV K103N 71 76 NNRTI;RT 159;93 164;114 HIV infections 124 138 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. The RT K103N mutation is selected by the NNRTI class of HIV drugs. 2006 AIDS research and therapy Abstract HIV K103N 7 12 NNRTI;RT 41;4 46;6 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. Abacavir resistance was characterized by the accumulation of the M184V, Y115F, and K65R mutations in the abacavir culture, while the M184V and L74V mutations were selected in combination with lamivudine. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65R;L74V;M184V;M184V;Y115F 83;143;65;133;72 87;147;70;138;77 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. At intermediate concentrations of emtricitabine and tenofovir, viruses harboring the K65R mutation or a novel K65N and K70R double mutation grew before they gave rise to mutants with K65R and M184V/I double mutations at higher emtricitabine concentrations. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65N;K65R;K65R;K70R;M184I;M184V 110;85;183;119;192;192 114;89;187;123;199;199 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. At low concentrations of emtricitabine and tenofovir, the M184I mutation appeared first, followed by the K65R mutation, in a subset of viruses. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184I 105;58 109;63 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. Emtricitabine- and lamivudine-resistant HIV-1 isolates with the M184I or M184V mutation in reverse transcriptase were readily selected in the cultures with emtricitabine alone, lamivudine alone, and the two drug combinations and conferred high-level resistance to emtricitabine and lamivudine. 2006 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V 64;73 69;78 RT 91 112 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. In conclusion, these studies show that HIV-1 mutants with a K65R and M184V genotype are generated under maximum selection pressure from the combination of tenofovir and emtricitabine. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V 60;69 64;74 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. In contrast, viral growth was markedly impaired in the cultures with high tenofovir concentrations, even in the presence of K65R. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65R 124 128 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. Tenofovir-resistant HIV-1 isolates with the K65R mutation occurred in both the culture with tenofovir alone and the culture with the combination of emtricitabine and tenofovir. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65R 44 48 16982781 In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. The S68N and S68K mutations were also observed in the tenofovir cultures, with no detectable impact on resistance, suggesting a possible compensatory role in viral fitness. 2006 Antimicrobial agents and chemotherapy Abstract HIV S68K;S68N 13;4 17;8 16989618 A rapid and sensitive real-time PCR assay for the K65R drug resistance mutation in SIV reverse transcriptase. In testing longitudinal plasma specimens from four SIV-infected macaques that received an active daily regimen of 30 mg/kg of tenofovir subcutaneously, the assay was able to detect K65R-positive viruses in all animals within 1-7 weeks after treatment began. 2006 AIDS research and human retroviruses Abstract HIV K65R 181 185 16989618 A rapid and sensitive real-time PCR assay for the K65R drug resistance mutation in SIV reverse transcriptase. To have this capability, we developed a real-time PCR-based assay for the detection of the SIV K65R reverse transcriptase mutation, a key marker for reduced susceptibility to tenofovir. 2006 AIDS research and human retroviruses Abstract HIV K65R 95 99 RT 100 121 16989618 A rapid and sensitive real-time PCR assay for the K65R drug resistance mutation in SIV reverse transcriptase. We propose the SIV K65R real-time PCR assay provides improved sensitivity and simplicity in studying tenofovir resistance in macaque models. 2006 AIDS research and human retroviruses Abstract HIV K65R 19 23 16995739 Molecular dynamic and free energy studies of primary resistance mutations in HIV-1 protease-ritonavir complexes. To understand the basis of drug resistance of the HIV-1 protease, molecular dynamic (MD) and free energy calculations of the wild-type and three primary resistance mutants, V82F, I84V, and V82F/I84V, of HIV-1 protease complexed with ritonavir were carried out. 2006 Journal of chemical information and modeling Abstract HIV I84V;I84V;V82F;V82F 179;194;173;189 183;198;177;193 PR;PR 56;209 64;217 16998878 Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso. 10/17 (58.82%) presented virus with minor protease (PR) mutations [L63P: 5/17 patients (29.41%), V77I: 3/17 patients (17.64%), L10I: 2/17 patients (11.76%)]. 2006 Journal of medical virology Abstract HIV L10I;L63P;V77I 127;67;97 131;71;101 PR;PR 42;52 50;54 16998878 Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso. Among 17 non-highly active antiretroviral therapy (HAART) patients, 3/17 (17.64%) presented virus with reverse transcriptase (RT) mutations [V118I: 1/17 patients (5.88%), V179E: 2/17 patients (11.76%)]. 2006 Journal of medical virology Abstract HIV V118I;V179E 141;171 146;176 RT;RT 103;126 124;128 16998878 Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso. Among six HAART-treated patients, 6/6 and 3/6 had M36I and L63LP protease minor subtypes, respectively; and only two (33.33%) presented virus with K103N mutation. 2006 Journal of medical virology Abstract HIV K103N;L63L;L63P;M36I 147;59;59;50 152;64;64;54 PR 65 73 16998878 Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso. As expected, all patients presented the common (non-B subtype) M36I polymorphism and 26/29 (90%) the K20I mutation. 2006 Journal of medical virology Abstract HIV K20I;M36I 101;61 105;67 16998878 Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso. During the same period, the twin mother presented a different NNRTI-mutation (V106I), thus suggesting that the different blood drug concentration may determine a different drug-resistance pathway. 2006 Journal of medical virology Abstract HIV V106I 78 83 NNRTI 62 67 16998878 Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso. Two twins showed, 6 months after birth, a NNRTI-mutation (Y181C/Y). 2006 Journal of medical virology Abstract HIV Y181C;Y181Y 58;58 65;65 NNRTI 42 47 17005757 MultiCode-RTx real-time PCR system for detection of subpopulations of K65R human immunodeficiency virus type 1 reverse transcriptase mutant viruses in clinical samples. We report a real-time PCR assay capable of detecting drug-resistant human immunodeficiency virus type 1 reverse transcriptase K65R mutant virus at a level of 0.5% in polymorphic patient plasma specimens. 2006 Journal of clinical microbiology Abstract HIV K65R 126 130 RT 104 125 17009933 Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone. FTC selects for M184V mutation less frequently than lamivudine. 2006 Expert review of anti-infective therapy Abstract HIV M184V 16 21 17009933 Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone. Resistance mutation K65R is selected for by tenofovir and confers a two- to fourfold reduced susceptibility to this drug. 2006 Expert review of anti-infective therapy Abstract HIV K65R 20 24 17009933 Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone. The incidence of K65R is low (3%) and has not been observed in clinical trials with the concomitant use of tenofovir and FTC. 2006 Expert review of anti-infective therapy Abstract HIV K65R 17 21 17015626 High prevalence of the K65R mutation in human immunodeficiency virus type 1 subtype C isolates from infected patients in Botswana treated with didanosine-based regimens. The K65R mutation was selected either alone or together with the Q151M, S68G, or F116Y substitution in viruses from seven such individuals. 2006 Antimicrobial agents and chemotherapy Abstract HIV F116Y;K65R;Q151M;S68G 81;4;65;72 86;8;70;76 17015626 High prevalence of the K65R mutation in human immunodeficiency virus type 1 subtype C isolates from infected patients in Botswana treated with didanosine-based regimens. The results of in vitro passage experiments were consistent with an apparent increased propensity of subtype C viruses to develop the K65R substitution. 2006 Antimicrobial agents and chemotherapy Abstract HIV K65R 134 138 17019361 Genotype and phenotype patterns of drug-resistant HIV-1 subtype B' (Thai B) isolated from patients failing antiretroviral therapy in China. Five codons (101, 103, 108, 181, and 190) were involved in the NVP-resistant mutations, and K103N and Y181C mutations were predominant in these isolates. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;Y181C 92;102 97;107 17020946 Indolopyridones inhibit human immunodeficiency virus reverse transcriptase with a novel mechanism of action. While INDOPY-1 susceptibility is unaffected by mutations associated with NNRTI or multidrug NRTI resistance, mutations M184V and Y115F are associated with decreased susceptibility, and mutation K65R confers hypersusceptibility to INDOPY-1. 2006 Journal of virology Abstract HIV K65R;M184V;Y115F 194;119;129 198;124;134 NNRTI;NRTI 73;92 78;96 1703563 Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. A point mutation of His 539----Asn produced an enzyme with a marked thermolabile RNase H function (nine-fold increase in inactivation), whereas RT function was only marginally more labile than that of the wild-type (two-fold). 1991 The Journal of general virology Abstract HIV H539N 20 34 RT 144 146 1703563 Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. A second mutation, His 539----Asp, impaired both enzyme activities to a similar degree (four- to five-fold). 1991 The Journal of general virology Abstract HIV H539D 19 33 Asp 30 33 17042328 Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors: synthesis, biological evaluation and binding mode studies of new derivatives at indole-2-carboxamide. Several new compounds were highly active in lymphocytes infected with primary isolates carrying the K103N-V1081-M184V and L1001-V1081 mutations. 2006 Antiviral chemistry & chemotherapy Abstract HIV K103N;M184V 100;112 105;117 17042328 Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors: synthesis, biological evaluation and binding mode studies of new derivatives at indole-2-carboxamide. We synthesized new NNRTIs of the indolyl aryl sulphone (IAS) family, which are endowed with high antiviral potency against HIV-1 wt (wild-type), and the Y181C and K103N-Y181C drug resistant mutant strains. 2006 Antiviral chemistry & chemotherapy Abstract HIV K103N;Y181C;Y181C 163;153;169 168;158;174 NNRTI 19 25 17045121 Frequency of protease and reverse transcriptase drug resistance mutations in naive HIV-infected patients. RESULTS: One of 36 isolates (2.8%) had the M184V resistance mutation to nucleoside retrotranscriptase inhibitors. 2006 Archives of medical research Abstract HIV M184V 43 48 17046266 The triphosphate of beta-D-4'-C-ethynyl-2',3'-dideoxycytidine is the preferred enantiomer substrate for HIV reverse transcriptase. The enantioselective synthesis of the beta-d (1) enantiomer of 4'-C-ethynyl-2',3'-dideoxycytidine confirms an earlier stereochemical assignment that was strictly based on the ability of HIV reverse transcriptase and its M184V mutant to discriminate between the d- and l-configuration of nucleoside 5'-triphosphates. 2007 Bioorganic & medicinal chemistry Abstract HIV M184V 220 225 RT 190 211 17048958 Computational study of the interaction between TIBO inhibitors and Y181 (C181), K101, and Y188 amino acids. The natural bond orbital (NBO) and atoms in molecules (AIM) methods indicate that not only does the Y181C mutation lead to loss of favorable interactions between the TIBO side chains and tyrosine, but it also affects the interaction between the inhibitor and K101 and Y188. 2006 The journal of physical chemistry. B Abstract HIV Y181C 100 105 17053312 Quantitative SNP-detection method for estimating HIV-1 replicative fitness: application to protease inhibitor-resistant viruses. Almost identical results were obtained for L90M-mutated HIV-1 with or without saquinavir. 2006 Microbiology and immunology Abstract HIV L90M 43 47 17053312 Quantitative SNP-detection method for estimating HIV-1 replicative fitness: application to protease inhibitor-resistant viruses. HIV-1 can survive under indinavir pressure by acquiring M46I mutation, as with acquisition of the L90M mutation under saquinavir pressure. 2006 Microbiology and immunology Abstract HIV L90M;M46I 98;56 102;60 17053312 Quantitative SNP-detection method for estimating HIV-1 replicative fitness: application to protease inhibitor-resistant viruses. In contrast, the fraction of M46I-mutated virus increased to >90% at passage #5 in the presence of 26.4 nM indinavir. 2006 Microbiology and immunology Abstract HIV M46I 29 33 17053312 Quantitative SNP-detection method for estimating HIV-1 replicative fitness: application to protease inhibitor-resistant viruses. Using this new competitive growth assay, replicative fitness of drug-resistant HIV-1 containing an M46I amino acid mutation in the protease was assessed in the presence or absence of indinavir. 2006 Microbiology and immunology Abstract HIV M46I 99 103 PR 131 139 17053312 Quantitative SNP-detection method for estimating HIV-1 replicative fitness: application to protease inhibitor-resistant viruses. Without indinavir, replicative fitness of wild-type HIV-1 surpassed that of M46I-mutated HIV-1, and the fraction of mutated virus was reduced to about 10% at passage #9. 2006 Microbiology and immunology Abstract HIV M46I 76 80 17053352 Resistance profile of a neutralizing anti-HIV monoclonal antibody, KD-247, that shows favourable synergism with anti-CCR5 inhibitors. A pseudotyped virus with the G314E mutation was highly resistant to KD-247. 2006 AIDS (London, England) Abstract HIV G314E 29 34 17053352 Resistance profile of a neutralizing anti-HIV monoclonal antibody, KD-247, that shows favourable synergism with anti-CCR5 inhibitors. RESULTS: At passage 8 of the culture in the presence of 1000 mug/ml KD-247, one amino acid substitution, Gly to Glu at position 314 (G314E), was identified in the V3-tip of gp120. 2006 AIDS (London, England) Abstract HIV G314E;G314E 133;105 138;131 gp120 173 178 17055529 Site-directed mutagenesis in the fingers subdomain of HIV-1 reverse transcriptase reveals a specific role for the beta3-beta4 hairpin loop in dNTP selection. The K65A mutant behaved similarly to the deletion mutant displaying dependence on Watson-Crick hydrogen bonding, increased fidelity and reduced dNTP-binding, while the K65R was more akin to wild-type enzyme. 2007 Journal of molecular biology Abstract HIV K65A;K65R 4;168 8;172 17055529 Site-directed mutagenesis in the fingers subdomain of HIV-1 reverse transcriptase reveals a specific role for the beta3-beta4 hairpin loop in dNTP selection. Two substitution mutants, K65R and K65A were studied. 2007 Journal of molecular biology Abstract HIV K65A;K65R 35;26 39;30 17056061 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097. HBY 097 makes a hydrogen bond with the thiol group of Cys181 that helps the drug retain potency against the Tyr181Cys mutation. 2007 Journal of molecular biology Abstract HIV Y181C 108 117 17056061 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097. Lys103Asn and Tyr181Cys are the two mutations frequently observed in patients exposed to various non-nucleoside reverse transcriptase inhibitor drugs (NNRTIs). 2007 Journal of molecular biology Abstract HIV K103N;Y181C 0;14 9;23 NNRTI;NNRTI 97;151 133;157 17056061 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097. The structure of the unliganded double mutant HIV-1 RT showed that Lys103Asn mutation facilitates coordination of a sodium ion with Lys101 O, Asn103 N and O(delta1), Tyr188 O(eta), and two water molecules. 2007 Journal of molecular biology Abstract HIV K103N 67 76 RT 52 54 17056061 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097. We have determined crystal structures of Lys103Asn/Tyr181Cys mutant HIV-1 RT with and without a bound non-nucleoside inhibitor (HBY 097, (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthio-methyl)-3,4-dihydroquinoxalin-2(1H)-thione) at 3.0 A and 2.5 A resolution, respectively. 2007 Journal of molecular biology Abstract HIV K103C;K103N;K103Y;Y181C 41;41;41;51 50;50;50;60 RT 74 76 17057609 Tenofovir disoproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients: virologic, immunologic, and morphologic changes--a 96-week analysis. No patient developed the K65R mutation. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 25 29 17057610 Virologic response of zidovudine, lamivudine, and tenofovir disoproxil fumarate combination in antiretroviral-naive HIV-1-infected patients. Six viral failures occurred, including 2 with K65R mutations (alone or associated with Y115F and M184V). 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;M184V;Y115F 46;97;87 50;102;92 17062187 Antiretroviral drug-resistant HIV-2 infection--a new therapeutic dilemma. Mutations at codons M184V and Q151M conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-1 infection were detected, as were mutations at codons V71I and L90M implying indinavir and nelfinavir resistance as well. 2006 International journal of STD & AIDS Abstract HIV L90M;M184V;Q151M;V71I 184;20;30;175 188;25;35;179 NRTI;NRTI 61;106 93;111 HIV infections 116 131 17066895 Rapid propagation of low-fitness drug-resistant mutants of human immunodeficiency virus type 1 by a streptococcal metabolite sparsomycin. In addition to wild-type HIV-1, sparsomycin also accelerated the replication of low-fitness, drug-resistant mutants carrying either D30N or L90M within HIV-1 protease, which are frequently found mutations in HIV-1-infected patients on highly active antiretroviral therapy (HAART). 2006 Antiviral chemistry & chemotherapy Abstract HIV D30N;L90M 132;140 136;144 PR 158 166 HIV infections 208 222 17066895 Rapid propagation of low-fitness drug-resistant mutants of human immunodeficiency virus type 1 by a streptococcal metabolite sparsomycin. Of particular interest was that replication enhancement appeared profound when HIV-1 such as the L90M-carrying mutant displayed relatively slower replication kinetics. 2006 Antiviral chemistry & chemotherapy Abstract HIV L90M 97 101 17067581 Modulation of HIV-1 Rev protein abundance and activity by polyubiquitination with unconventional Lys-33 branching. Mutation of Rev Lys-115 to arginine reduces markedly the steady state amount of the protein, but does not impair its ability to export RNA via the Rev response element. 2006 FEBS letters Abstract HIV K115R 16 35 Rev;Rev 12;147 15;150 17070543 Mutational patterns associated with the 69 insertion complex in multi-drug-resistant HIV-1 reverse transcriptase that confer increased excision activity and high-level resistance to zidovudine. Further studies, using recombinant RTs obtained by site-directed mutagenesis, revealed that M41L, A62V and in a lesser extent K70R, were the key mutations that together with T69S, T215Y and the dipeptide insertion conferred high levels of ATP-dependent phosphorolytic activity on AZT and d4T-terminated primers. 2007 Journal of molecular biology Abstract HIV A62V;K70R;M41L;T215Y;T69S 98;126;92;180;174 102;130;96;185;178 RT 35 38 17070543 Mutational patterns associated with the 69 insertion complex in multi-drug-resistant HIV-1 reverse transcriptase that confer increased excision activity and high-level resistance to zidovudine. Mutations T69S and T215Y and a dipeptide insertion. 2007 Journal of molecular biology Abstract HIV T215Y;T69S 19;10 24;14 17070543 Mutational patterns associated with the 69 insertion complex in multi-drug-resistant HIV-1 reverse transcriptase that confer increased excision activity and high-level resistance to zidovudine. Structural analysis of the location of the implicated amino acid substitutions revealed a coordinated effect of M41L and A62V on the positioning of the beta3-beta4 hairpin loop, which plays a key role in the resistance mechanism. 2007 Journal of molecular biology Abstract HIV A62V;M41L 121;112 125;116 17072129 Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. BACKGROUND: We retrospectively studied the effect of the lamivudine-induced reverse transcription mutation M184V on selection of thymidine analog mutations (TAMs) in HIV subtype C-infected children and on clinical outcome. 2006 The Pediatric infectious disease journal Abstract HIV M184V 107 112 RT 76 97 17072129 Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. In M184V-containing samples, we found large reductions in susceptibility to lamivudine and emtricitabine but not to other NRTIs. 2006 The Pediatric infectious disease journal Abstract HIV M184V 3 8 NRTI 122 127 17072129 Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. RESULTS: M184V developed in 18 of 22 of children who had received only zidovudine/stavudine + lamivudine + PI/NNRTI during a mean of 23.2 +/- 3.2 months versus in 3 of 14 children treated with other drugs and/or having multiple regimen changes (P = 0.001). 2006 The Pediatric infectious disease journal Abstract HIV M184V 9 14 NNRTI;PI 110;107 115;109 17072129 Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. This is likely the result of an increased susceptibility to thymidine analog (zidovudine) in the context of M184V documented here for the first time in subtype C-infected children. 2006 The Pediatric infectious disease journal Abstract HIV M184V 108 113 17072129 Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. When both M184V + T215Y occurred, susceptibility to zidovudine was substantially increased. 2006 The Pediatric infectious disease journal Abstract HIV M184V;T215Y 10;18 15;23 17072129 Diminished selection for thymidine-analog mutations associated with the presence of M184V in Ethiopian children infected with HIV subtype C receiving lamivudine-containing therapy. When T215Y was present without M184V, susceptibility to zidovudine was reduced 8-fold. 2006 The Pediatric infectious disease journal Abstract HIV M184V;T215Y 31;5 36;10 1707532 Detection of human immunodeficiency virus type 1 clinical isolates with reduced sensitivity to zidovudine and dideoxyinosine by RNA.RNA hybridization. The drug sensitivity system was confirmed by showing that mutations in the HIV reverse transcriptase gene from a ZDV-resistant isolate resulted in four amino acid changes (Leu-125----Trp, Ile-142----Val, Thr-215----Tyr, and Pro-294----Thr) including one change (Thr-215----Tyr) that has been previously reported to be associated with resistance. 1991 Proc Natl Acad Sci U S A Abstract HIV I142V;L125W;P294T;T215Y;T215Y 188;172;224;204;262 202;186;238;218;276 RT 79 100 17075395 Differential impact of thymidine analogue mutations on emtricitabine and lamivudine susceptibility. For samples with K65R, L74I/V, or Q151M mutations, the phenotypic impact was similar, as the mean fold-change was not significantly different between drugs. 2006 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;L74I;L74V;Q151M 17;23;23;34 21;29;29;39 17083034 Prevalence of primary HIV-1 drug resistance among recently infected adolescents: a multicenter adolescent medicine trials network for HIV/AIDS interventions study. Eight (15%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations, with the majority (6) having the K103N mutation; 2 (4%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; and 2 (4%) had protease inhibitor (PI) mutations. 2006 The Journal of infectious diseases Abstract HIV K103N 114 119 NNRTI;NRTI;PR;NNRTI;NRTI;PI 16;141;217;63;185;237 51;173;225;68;189;239 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. A mutation of amino acid 73 (I73V) of HIV-2 capsid renders this virus Lv2-insensitive. 2006 Retrovirology Abstract HIV I73V 29 33 Capsid 44 50 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. HIV-2 envelope protein (Env42S)-pseudotyped HIV-2/I73V particles revealed a 9.3 fold increase in infection in TZM cells but remained restricted in TZM-huTRIM5alpha cells (80.6 fold inhibition) clearly indicating that at least two restriction factors, TRIM5alpha and Lv2, act on incoming HIV-2 particles. 2006 Retrovirology Abstract HIV I73V 50 54 Env;Env 24;6 27;14 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. Lv2-insensitive VSV-G pseudotyped HIV-2/I73V particles showed a similar restriction to infection as did HIV-2[VSV-G] particles (4 fold inhibition). 2006 Retrovirology Abstract HIV I73V 40 44 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. By comparison, K65R RT demonstrated 12.4-, 12.0-, and 13.1-fold-higher levels of resistance, respectively, toward the same analogs. 2007 Antimicrobial agents and chemotherapy Abstract HIV K65R 15 19 RT 20 22 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. Compared to the WT enzyme, K70E RT showed 2.1-, 2.3-, and 3.5-fold-higher levels of resistance toward TNV-diphosphate, carbovir-TP, and 3TC-TP, respectively. 2007 Antimicrobial agents and chemotherapy Abstract HIV K70E 27 31 RT 32 34 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. NRTI-TP discrimination by the K70E (and K65R) mutation was primarily due to decreased rates of NRTI-TP incorporation and not to changes in analog binding affinity. 2007 Antimicrobial agents and chemotherapy Abstract HIV K65R;K70E 40;30 44;34 NRTI;NRTI 0;95 4;99 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. Pre-steady-state kinetic experiments demonstrate that the K70E mutation in HIV-1 RT allows the enzyme to discriminate between the natural deoxynucleoside triphosphate substrate and the NRTI triphosphate (NRTI-TP). 2007 Antimicrobial agents and chemotherapy Abstract HIV K70E 58 62 NRTI;NRTI;RT 185;204;81 189;208;83 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. Taken together, these findings indicate that the K70E mutation, like the K65R mutation, reduces susceptibility to NRTI by selectively decreasing NRTI-TP incorporation and is antagonistic to TAM-mediated nucleotide excision. 2007 Antimicrobial agents and chemotherapy Abstract HIV K65R;K70E 73;49 77;53 NRTI;NRTI 114;145 118;149 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. The K65R and K70E mutations also profoundly impaired the ability of RT to excise 3'-azido-2',3'-dideoxythymidine monophosphate (AZT-MP) and other NRTI-MP from the 3' end of a chain-terminated primer. 2007 Antimicrobial agents and chemotherapy Abstract HIV K65R;K70E 4;13 8;17 NRTI;RT 146;68 150;70 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. The K70E mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has become more prevalent in clinical samples, particularly in isolates derived from patients for whom triple-nucleoside regimens that include tenofovir (TNV), abacavir, and lamivudine (3TC) failed. 2007 Antimicrobial agents and chemotherapy Abstract HIV K70E 4 8 RT;RT 65;88 86;90 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. To elucidate the molecular mechanism by which this mutation confers resistance to these nucleoside RT inhibitors (NRTI), we conducted detailed biochemical analyses comparing wild-type (WT), K70E, and K65R HIV-1 RT. 2007 Antimicrobial agents and chemotherapy Abstract HIV K65R;K70E 200;190 204;194 NRTI;RT;RT 114;99;211 118;101;213 17088490 Molecular mechanism by which the K70E mutation in human immunodeficiency virus type 1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. When introduced into an enzyme with the thymidine analog mutations (TAMs) M41L, L210W, and T215Y, the K70E mutation inhibited ATP-mediated excision of AZT-MP. 2007 Antimicrobial agents and chemotherapy Abstract HIV K70E;L210W;M41L;T215Y 102;80;72;91 106;85;78;96 17089433 Arylthiopyrrole (AThP) derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis, structure-activity relationships, and docking studies (part 1). A selected number of AThPs (4k and 5a,e) were tested against clinically relevant drug-resistant forms of recombinant reverse transcriptase (rRT) carrying the K103N and Y181I mutations. 2006 ChemMedChem Abstract HIV K103N;Y181I 158;168 163;173 RT 117 138 17089433 Arylthiopyrrole (AThP) derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis, structure-activity relationships, and docking studies (part 1). Carbamate 5e showed an approximate 240-fold decrease in activity against Y181I, but only a 10-fold loss in potency against the K103N rRT form. 2006 ChemMedChem Abstract HIV K103N;Y181I 127;73 132;78 17089434 Arylthiopyrrole (AThP) derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis, structure-activity relationships, and docking studies (part 2). This compound and its precursor 18b retained interesting activities against clinically relevant drug-resistant RT forms carrying K103N, Y181I, and L100I mutations. 2006 ChemMedChem Abstract HIV K103N;L100I;Y181I 129;147;136 134;152;141 RT 111 113 17090696 HIV-1 protease catalytic efficiency effects caused by random single amino acid substitutions. In particular, the mutation N88D, lethal for the wild-type protease, restored the wild-type catalytic efficiency when combined with the highly deleterious mutation D30N. 2007 Molecular biology and evolution Abstract HIV D30N;N88D 164;28 168;32 PR 59 67 17090696 HIV-1 protease catalytic efficiency effects caused by random single amino acid substitutions. When a second random mutagenesis library was constructed from an HIV-1 protease carrying a highly deleterious single mutation (D30N), a higher proportion of mutations with neutral or beneficial effect were found, 26% and 9%, respectively. 2007 Molecular biology and evolution Abstract HIV D30N 127 131 PR 71 79 17092531 Specific amino acids in the N-terminus of the gp41 ectodomain contribute to the stabilization of a soluble, cleaved gp140 envelope glycoprotein from human immunodeficiency virus type 1. Soluble, stabilized, proteolytically cleaved, trimeric gp140 proteins can be generated by engineering an intermolecular disulfide bond between gp120 and gp41 (SOS), combined with a single residue change, I559P, within gp41 (SOSIP). 2007 Virology Abstract HIV I559P 204 209 gp120;gp140;gp41;gp41 143;55;153;218 148;60;157;222 17096474 The M184V mutation: what it does, how to prevent it, and what to do with it when it's there. The M184V mutation is selected by lamivudine (3TC) and emtricitabine (FTC) and is a common mutation in HIV-infected patients. 2006 The AIDS reader Abstract HIV M184V 4 9 HIV infections 103 115 17096474 The M184V mutation: what it does, how to prevent it, and what to do with it when it's there. Virus with the M184V mutation has a high level of resistance to 3TC and FTC but has been shown to have favorable effects on the susceptibility of some other NRTIs and can delay clinical and immunologic progression by decreasing viral fitness. 2006 The AIDS reader Abstract HIV M184V 15 20 NRTI 157 162 17096474 The M184V mutation: what it does, how to prevent it, and what to do with it when it's there. While it is always better not to have any drug resistance so that 3TC and FTC are available as active antiretroviral agents, it is important to take advantage of the beneficial effects of the M184V mutation when it is present. 2006 The AIDS reader Abstract HIV M184V 192 197 17101675 Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication. In contrast, isolates with the I84A mutation exhibited>or=33-fold median increased levels of resistance to nelfinavir, indinavir, amprenavir, ritonavir, lopinavir, saquinavir, and atazanavir. 2007 Antimicrobial agents and chemotherapy Abstract HIV I84A 31 35 17101675 Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication. Isolates with the I84A or I84C mutation tended to be more resistant than the isolates with the I84V mutation. 2007 Antimicrobial agents and chemotherapy Abstract HIV I84A;I84C;I84V 18;26;95 22;30;99 17101675 Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication. Modeling of the structure of the mutant proteases indicated that the I84V, I84C, and I84A mutations all create unoccupied volume in the active site, with I84A introducing the greatest change in the accessible surface area from that of the wild-type structure. 2007 Antimicrobial agents and chemotherapy Abstract HIV I84A;I84A;I84C;I84V 85;154;75;69 89;158;79;73 PR 40 49 17101675 Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication. The mutants with I84C displayed high-level resistance (median, at least 56-fold) to nelfinavir and saquinavir, but the majority remained susceptible to lopinavir. 2007 Antimicrobial agents and chemotherapy Abstract HIV I84C 17 21 17101675 Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication. Two novel human immunodeficiency virus protease mutations, I84C and I84A, were identified in patient isolates. 2007 Antimicrobial agents and chemotherapy Abstract HIV I84A;I84C 68;59 72;63 PR 39 47 17108020 Precise identification of a human immunodeficiency virus type 1 antigen processing mutant. Here we investigate the association between E169D and HLA-B*0702 for immune escape via the SM9 epitope. 2007 Journal of virology Abstract HIV E169D 44 49 17108020 Precise identification of a human immunodeficiency virus type 1 antigen processing mutant. Polymorphism E169D in HIV-1 reverse transcriptase (RT) is significantly associated with HLA-B*0702 in HIV-1-infected individuals. 2007 Journal of virology Abstract HIV E169D 13 18 RT;RT 28;51 49;53 HIV infections 102 116 17108020 Precise identification of a human immunodeficiency virus type 1 antigen processing mutant. The E169D polymorphism also maps within and abrogates the recognition of an HLA-A*03-restricted RT epitope MR9. 2007 Journal of virology Abstract HIV E169D 4 9 RT 96 98 17109975 Highly selective action of triphosphate metabolite of 4'-ethynyl D4T: a novel anti-HIV compound against HIV-1 RT. 4'-Ed4TTP was also found to inhibit the 3TC (Lamivudine)-resistant RT mutant, M184V, with 3-fold less efficiency than the wild type (wt) RT. 2007 Antiviral research Abstract HIV M184V 78 83 RT;RT 67;137 69;139 17116674 Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. After 25 weeks, other cultures had developed I50V and I84V mutations. 2007 Antimicrobial agents and chemotherapy Abstract HIV I50V;I84V 45;54 49;58 17116674 Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. In contrast, no major PI mutations were selected in HIV-1 over this period except for D30N in the context of NFV selective pressure. 2007 Antimicrobial agents and chemotherapy Abstract HIV D30N 86 90 PI 22 24 17116674 Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. The acquisition of the I54M, I84V, L90M, and L99F mutations resulted in multi-PI-resistant viruses, conferring 10-fold to more than 100-fold resistance. 2007 Antimicrobial agents and chemotherapy Abstract HIV I54M;I84V;L90M;L99F 23;29;35;45 27;33;39;49 PI 78 80 17116674 Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. Within 10 to 15 weeks of serial passage, three major mutations--I54M, I82F, and L90M--arose in HIV-2 viral cultures exposed to APV, NFV, and IDV, whereas I82L was selected with TPV. 2007 Antimicrobial agents and chemotherapy Abstract HIV I54M;I82F;I82L;L90M 64;70;154;80 68;74;158;84 17116677 A novel nonnucleoside analogue that inhibits human immunodeficiency virus type 1 isolates resistant to current nonnucleoside reverse transcriptase inhibitors. A virus containing the double mutation V106I-Y181C emerged after 4 months, causing a sixfold increase in resistance. 2007 Antimicrobial agents and chemotherapy Abstract HIV V106I;Y181C 39;45 44;50 17116677 A novel nonnucleoside analogue that inhibits human immunodeficiency virus type 1 isolates resistant to current nonnucleoside reverse transcriptase inhibitors. RT mutations selected by VRX-480773 after 3 months of cell culture in the presence of 1 nM VRX-480773 carried the Y181C mutation, resulting in a less-than-twofold increase in resistance to the compound. 2007 Antimicrobial agents and chemotherapy Abstract HIV Y181C 114 119 RT 0 2 17116677 A novel nonnucleoside analogue that inhibits human immunodeficiency virus type 1 isolates resistant to current nonnucleoside reverse transcriptase inhibitors. Viruses containing additional mutations of D123G, F227L, and T369I emerged when the cultures were incubated with increasing concentrations of VRX-480773. 2007 Antimicrobial agents and chemotherapy Abstract HIV D123G;F227L;T369I 43;50;61 48;55;66 17117145 Selection and persistence of viral resistance in HIV-infected children after exposure to single-dose nevirapine. By 18 months of age, 11 of 24 infants with resistance had died and 1 still had the Y181C mutation. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Y181C 83 88 17117145 Selection and persistence of viral resistance in HIV-infected children after exposure to single-dose nevirapine. CONCLUSIONS: Resistant mutations were selected in half of the infants exposed to sd-NVP, but fewer were detected over time and, unlike the case in their mothers, Y181C dominated initially and persists. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Y181C 162 167 17117145 Selection and persistence of viral resistance in HIV-infected children after exposure to single-dose nevirapine. RESULTS: Of 53 HIV-infected infants, 24 (45.3%) had detectable resistance at their first visit, when the most frequent mutations were Y181C (75%), K103N (25%), and Y188C (12%). 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;Y181C;Y188C 147;134;164 152;139;169 HIV infections 15 27 17121220 [Background study of HIV-1 drug resistant mutations in treatment-naive patients in liaoning province]. Minor resistance mutation rate to protease inhibitors was 100%, including types of L63P (60.4%), V77I (60.4%), M36I/V (31.9%), A71V/T (22.0%), L10I (8.8%), and K20R (6.6%). 2006 Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae Abstract HIV A71T;A71V;K20R;L10I;L63P;M36I;M36V;V77I 127;127;160;143;83;111;111;97 133;133;164;147;87;117;117;101 PR 34 42 17121220 [Background study of HIV-1 drug resistant mutations in treatment-naive patients in liaoning province]. Only one sequence carried reverse transcriptase related resistance mutations M184I. 2006 Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae Abstract HIV M184I 77 82 RT 26 47 17121220 [Background study of HIV-1 drug resistant mutations in treatment-naive patients in liaoning province]. RESULTS: Totally 91 sequences were obtained, 3 of which displayed M46I mutations in the protease gene. 2006 Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae Abstract HIV M46I 66 70 PR 88 96 17121798 A single-nucleotide synonymous mutation in the gag gene controlling human immunodeficiency virus type 1 virion production. Furthermore, we have identified a synonymous mutation in nucleotide position 75 of the gag p17 gene (A426G) of HIV-1 that belongs to the CRF01_AE virus circulating in Thailand. 2007 Journal of virology Abstract HIV A426G 101 106 Gag 87 90 17121798 A single-nucleotide synonymous mutation in the gag gene controlling human immunodeficiency virus type 1 virion production. The replication-competent HIV-1 clone containing the A426G mutation demonstrated a dramatic reduction of virion production and perturbation of viral morphogenesis without affecting viral protein synthesis in cells. 2007 Journal of virology Abstract HIV A426G 53 58 17123566 Resistance of HIV-1 to the broadly HIV-1-neutralizing, anti-carbohydrate antibody 2G12. Moreover, we observed that the NL4.3-2G12-resistant virus, with the N295K mutation in gp120, became significantly more sensitive to several mannose-specific lectins. 2007 Virology Abstract HIV N295K 68 73 gp120 86 91 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. CONCLUSION: The forced evolution experiments indicate that the premature conformational switch of the T20-dependent HIV-1 Env variant (GIA-SKY) can be corrected by a second site mutation in Env (GIA-SKY-G431R) that affects the interaction with the CD4 receptor. 2006 Retrovirology Abstract HIV G431R 195 208 Env;Env 122;190 125;193 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Strikingly, 3 cultures revealed the same single amino acid change in the CD4 binding region of Env (glycine at position 431 substituted for arginine: G431R). 2006 Retrovirology Abstract HIV G431R;G431R 150;100 155;149 Env 95 98 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The escape variant was more sensitive to an antibody acting on an early gp41 intermediate, suggesting that the G431R mutation helps preserve a pre-fusion Env conformation, similar to T20 action. 2006 Retrovirology Abstract HIV G431R 111 116 gp41;Env 72;154 76;157 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The GIA-SKY-G431R escape variant produces an Env protein that exhibits reduced syncytia formation and reduced cell-cell fusion activity. 2006 Retrovirology Abstract HIV G431R 4 17 Env 45 48 17137594 Identification of the LEDGF/p75 binding site in HIV-1 integrase. Comparison of the wild-type IN-LEDGF/p75 co-crystal structure with that of the modelled structure of the IN(Q168A) and IN(W131A) mutant integrases corroborated our experimental data. 2007 Journal of molecular biology Abstract HIV Q168A;W131A 108;122 113;127 IN;IN;IN;IN 136;28;105;119 146;30;107;121 17137594 Identification of the LEDGF/p75 binding site in HIV-1 integrase. Due to impaired integration, an HIV-1 strain containing the W131A mutation in IN displays reduced replication capacity, whereas virus carrying IN(Q168A) is replication defective. 2007 Journal of molecular biology Abstract HIV Q168A;W131A 146;60 151;65 IN;IN 78;143 80;145 17137594 Identification of the LEDGF/p75 binding site in HIV-1 integrase. IN(W131A), IN(I161A), IN(R166A), IN(Q168A) and IN(E170A) are impaired for interaction with LEDGF/p75, but retain 3' processing and strand transfer activities. 2007 Journal of molecular biology Abstract HIV E170A;I161A;Q168A;R166A;W131A 50;14;36;25;3 55;19;41;30;8 IN;IN;IN;IN;IN 0;11;22;33;47 2;13;24;35;49 17137594 Identification of the LEDGF/p75 binding site in HIV-1 integrase. We have subsequently shown that IN carrying the Q168A mutation remains enzymatically active but is impaired for interaction with LEDGF/p75. 2007 Journal of molecular biology Abstract HIV Q168A 48 53 IN 32 34 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. Certain mutants of Vpr, such as R77Q and I74A, identified in long-term nonprogressors, have been proposed to inefficiently induce apoptosis while activating the G2 checkpoint in a normal manner. 2006 PLoS pathogens Abstract HIV I74A;R77Q 41;32 45;36 Vpr 19 22 17141805 Analysis of amino acids in the beta7-beta8 loop of human immunodeficiency virus type 1 reverse transcriptase for their role in virus replication. Mutating asparagine 136 to alanine (N136A) reduced viral infectivity and enzyme activity dramatically. 2007 Journal of molecular biology Abstract HIV N136A;N136A 36;9 41;34 17141805 Analysis of amino acids in the beta7-beta8 loop of human immunodeficiency virus type 1 reverse transcriptase for their role in virus replication. Subunit-specific mutagenesis demonstrated that the presence of the N136A mutation in the p51 subunit alone was sufficient to cause degradation of RT within the virus particle. 2007 Journal of molecular biology Abstract HIV N136A 67 72 RT 146 148 17141805 Analysis of amino acids in the beta7-beta8 loop of human immunodeficiency virus type 1 reverse transcriptase for their role in virus replication. The N136A mutation appeared to destabilize the RT heterodimer and render both the p66 and p51 subunits susceptible to aberrant cleavage by the viral protease. 2007 Journal of molecular biology Abstract HIV N136A 4 9 PR;RT 149;47 157;49 17147507 Natural polymorphisms of HIV type 2 pol sequences from drug-naive individuals. In particular, the M46I substitution in the protease was detected in 90% of the sequences analyzed, which, together with the other substitutions identified, may indicate a reduced susceptibility of HIV-2-infected drug-naive patients to PI. 2006 AIDS research and human retroviruses Abstract HIV M46I 19 23 PR;PI 44;236 52;238 17150652 Replication-defective HIV isolated from seronegative individuals at high risk for HIV infection. These results indicate that the A75G mutation is attributable to the long-term sero-negativity of individuals at high risk of HIV-1 infection and suggest a novel mechanism that regulates HIV production. 2005 Nucleic acids symposium series (2004) Abstract HIV A75G 32 36 HIV infections 126 141 17150652 Replication-defective HIV isolated from seronegative individuals at high risk for HIV infection. We found A to G mutation at the nucleotide position 75 of gag p17 gene (A75G) not changing the amino acid sequence. 2005 Nucleic acids symposium series (2004) Abstract HIV A75G 72 76 Gag 58 61 17157017 Structure-activity relationship in the 3-iodo-4-phenoxypyridinone (IOPY) series: The nature of the C-3 substituent on anti-HIV activity. As part of a systematic SAR study on the 3-iodo-4-phenoxypyridinone 3 (IOPY) type non-nucleoside reverse transcriptase inhibitors, the analogues 4a-4z bearing different C-3 substituents were synthesized and evaluated for their anti-HIV activity against wild-type HIV-1 and four of the principal HIV mutant strains (K103N, Y181C, Y188L, and I100L). 2007 Bioorganic & medicinal chemistry letters Abstract HIV I100L;K103N;Y181C;Y188L 340;315;322;329 345;320;327;334 NNRTI 82 118 17170453 Capsid stability and replication of human immunodeficiency virus type 1 are influenced critically by charge and size of Gag residue 183. However, whereas biophysical analyses of mutant virions yielded wild-type-like particle sizes and densities, electron microscopy revealed aberrant core morphologies that could be attributed to either increased (D183N) or reduced (D183E) capsid stability. 2007 The Journal of general virology Abstract HIV D183E;D183N 230;211 235;216 Capsid 237 243 17170455 Structure-function analysis of the ribosomal frameshifting signal of two human immunodeficiency virus type 1 isolates with increased resistance to viral protease inhibitors. In patients undergoing viral protease (PR) inhibitor therapy, a p1/p6(gag) L449F cleavage site (CS) mutation is often observed in resistant isolates and frequently generates, at the nucleotide sequence level, a homopolymeric and potentially slippery sequence (UUUUCUU to UUUUUUU). 2007 The Journal of general virology Abstract HIV L449F 73 80 PR;Gag;Gag;PR 29;70;67;39 37;73;69;41 17172832 The role of Vpr in the regulation of HIV-1 gene expression. Expression of a mutant Vpr, with arginine 73 altered to serine, did not affect the ability of p21 to cause cells arrest or its sub-cellular localization. 2006 Cell cycle (Georgetown, Tex.) Abstract HIV R73S 33 62 Vpr 23 26 17179211 Mutations in the connection domain of HIV-1 reverse transcriptase increase 3'-azido-3'-deoxythymidine resistance. Mutational analysis showed that amino acid substitutions E312Q, G335C/D, N348I, A360I/V, V365I, and A376S were associated strongly with the observed increase in AZT resistance; several of these mutations also decreased RT template switching, suggesting that they alter the predicted balance between nucleotide excision and template RNA degradation. 2007 Proc Natl Acad Sci U S A Abstract HIV A360I;A360V;A376S;E312Q;G335C;G335D;N348I;V365I 80;80;100;57;64;64;73;89 87;87;105;62;71;71;78;94 RT 219 221 17188710 Point mutations in the HIV-1 matrix protein turn off the myristyl switch. Unexpectedly, the myristyl group of a revertant mutant with normal PM targeting properties (V7R,L21K) is also tightly sequestered and insensitive to PI(4,5)P(2) binding. 2007 Journal of molecular biology Abstract HIV L21K 96 100 PI 149 151 17191775 Non-nucleoside reverse transcriptase inhibitors (NNRTIs): past, present, and future. NNRTIs are notorious for rapidly leading to virus-drug resistance development, primarily based on the emergence of the K103N and Y181C mutations in the HIV-1 RT. 2004 Chemistry & biodiversity Abstract HIV K103N;Y181C 119;129 124;134 NNRTI;RT 0;158 6;160 17192300 The fitness cost of mutations associated with human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions. We also demonstrate that the fitness cost of M184V and K70R can be decreased or enhanced by other resistance mutations such as D67N and K219Q. 2007 Journal of virology Abstract HIV D67N;K219Q;K70R;M184V 127;136;55;45 131;141;59;50 17194486 Drug-resistant HIV-1 prevalence in patients newly diagnosed with HIV/AIDS in Japan. Twenty-three cases, including three recently infected patients, were infected with HIV-1 having major drug-resistance mutations, including M41L, D67N, L100I, K103N, V106A, M184I, M184V, L210W, and revertant mutations at the 215 codon in reverse transcriptase and M46I in protease encoding regions. 2007 Antiviral research Abstract HIV D67N;K103N;L100I;L210W;M184I;M184V;M41L;M46I;V106A 145;158;151;186;172;179;139;263;165 149;163;156;191;177;184;143;267;170 PR;RT 271;237 279;258 17197380 Fosamprenavir clinical study meta-analysis in ART-naive subjects: rare occurrence of virologic failure and selection of protease-associated mutations. RESULTS: FPV-associated resistance mutations were detected in 5/74 patients with VF, with 4/5 receiving unboosted FPV; in four patients viruses developed I54L or M and one developed the V32I+I47V combination. 2006 HIV clinical trials Abstract HIV I47V;I54L;V32I 191;154;186 195;158;190 17197808 Food and Drug Administration analysis of tipranavir clinical resistance in HIV-1-infected treatment-experienced patients. The most common protease mutations that developed in tipranavir-treated individuals who experienced virologic failure were L10I/V/S, I13V, L33V/I/F, M36V/I/L V82T, V82L, and I84V. 2007 AIDS (London, England) Abstract HIV I13V;I84V;L10I;L10S;L10V;L33F;L33I;L33V;M36I;M36L;M36V;V82L;V82T 133;174;123;123;123;139;139;139;149;149;149;164;158 137;178;131;131;131;147;147;147;157;157;157;168;162 PR 16 24 17201671 Immunovirologic characteristics of human immunodeficiency virus-infected patients consisting mainly of injecting drug users on highly active antiretroviral treatment with prolonged virologic failure. On the other hand, patients with K103N had the same level of CD4(+) cell count compared with patients without this mutation. 2006 Viral immunology Abstract HIV K103N 33 38 17201671 Immunovirologic characteristics of human immunodeficiency virus-infected patients consisting mainly of injecting drug users on highly active antiretroviral treatment with prolonged virologic failure. The patients showed a high accumulation of resistance-associated mutations, their CD4(+) cell count and viral load directly correlated with their respective values at initiation of therapy, and the presence of K103N was inversely associated with lower viral load. 2006 Viral immunology Abstract HIV K103N 210 215 17202191 RNA recognition mechanism of the minimal active domain of the human immunodeficiency virus type-2 nucleocapsid protein. The activity and three-dimensional structure of NCp8-f1/N11A, in which alanine is substituted for Asn(11) thereby affecting the conformation of the linker, was analyzed and compared with those of NCp8-f1. 2007 Journal of biochemistry Abstract HIV N11A 56 60 NC;NC 48;196 50;198 17205457 Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails. M184V was the most common nucleoside reverse-transcriptase inhibitor resistance mutation (observed in 89% of patients). 2007 Clinical infectious diseases Abstract HIV M184V 0 5 NRTI 26 58 17205457 Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails. Patients with an HIV-1 RNA load of >4 log copies/mL at the time of treatment failure had higher prevalence of thymidine analogue mutations (P=.041), K65R (P=.031), and Q151M (P=.008) mutations. 2007 Clinical infectious diseases Abstract HIV K65R;Q151M 149;168 153;173 17205457 Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails. Thymidine analogue mutations, K65R, and Q151M were observed in 37%, 6%, and 8% of patients, respectively. 2007 Clinical infectious diseases Abstract HIV K65R;Q151M 30;40 34;45 17207236 Human immunodeficiency virus-1 subtypes and antiretroviral drug resistance profiles among drug-naive Brazilian blood donors. Antiretroviral resistance to nucleoside RT inhibitor was observed in one sample (1.35%) showing M41L and T215S mutations. 2007 Transfusion Abstract HIV M41L;T215S 96;105 100;110 RT 40 42 17209764 Rate of virologic failure and selection of drug resistance mutations using different triple nucleos(t)ide analogue combinations in HIV-infected patients. Conversely, subjects who developed K65R did not accumulate TAMs. 2006 AIDS research and human retroviruses Abstract HIV K65R 35 39 17209764 Rate of virologic failure and selection of drug resistance mutations using different triple nucleos(t)ide analogue combinations in HIV-infected patients. M184V was the most frequent resistance mutation (75.4%), followed by T215Y (52.5%) and K65R (14.8%). 2006 AIDS research and human retroviruses Abstract HIV K65R;T215Y;M184V 87;69;0 91;74;5 17209764 Rate of virologic failure and selection of drug resistance mutations using different triple nucleos(t)ide analogue combinations in HIV-infected patients. Of note, K65R did not develop in patients taking AZT nor in those with prior thymidine-associated mutations (TAMs). 2006 AIDS research and human retroviruses Abstract HIV K65R 9 13 17209764 Rate of virologic failure and selection of drug resistance mutations using different triple nucleos(t)ide analogue combinations in HIV-infected patients. The presence of TAMs precluded the selection of K65R in patients treated with TDF. 2006 AIDS research and human retroviruses Abstract HIV K65R 48 52 17209774 N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. First, D30N was positively associated with N88D but negatively associated with N88S. 2006 AIDS research and human retroviruses Abstract HIV D30N;N88D;N88S 7;43;79 11;47;83 17209774 N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. In 16 patients having isolates with more than one combination of mutations at positions 30, 88, and 90, all exhibited one of the steps in the following progression: D30N-->D30N+N88D-->D30N+N88D+L90M-->D30N+N88D+L90M+(L33F+/-I84V or M46I/L+/-I54V). 2006 AIDS research and human retroviruses Abstract HIV I54V;M46I;M46L;D30N;D30N;I84V;L33F;L90M;L90M;N88D;N88D 241;232;232;201;165;224;218;211;194;206;177 245;238;238;205;169;228;221;215;198;210;181 17209774 N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. Second, D30N and L90M were negatively associated except in the presence of N88D, which facilitated the co-occurrence of D30N and L90M. 2006 AIDS research and human retroviruses Abstract HIV D30N;D30N;L90M;L90M;N88D 8;120;17;129;75 12;124;21;133;79 17209774 N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. Third, D30N+N88D+L90M formed a stable genetic backbone for the accumulation of additional protease inhibitor (PI) resistance mutations. 2006 AIDS research and human retroviruses Abstract HIV D30N;L90M;N88D 7;17;12 11;21;16 PR;PI 90;110 98;112 17209774 N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. To investigate the genetic mechanisms of multidrug resistance in protease isolates with the primary nelfinavir resistance mutation D30N, we analyzed patterns of protease mutations in 582 viruses with D30N from 460 persons undergoing HIV-1 genotypic resistance testing at Stanford University Hospital from 1997 to 2005. 2006 AIDS research and human retroviruses Abstract HIV D30N;D30N 131;200 135;204 PR;PR 65;161 73;169 17209775 Resistance mutational analysis of HIV type 1 subtype C among rural South African drug-naive patients prior to large-scale availability of antiretrovirals. Most of the RT sequences were wild-type, although V118I (8.5%) and Y318F (5.7%) associated with resistance to lamivudine and nevirapine, respectively, were observed. 2006 AIDS research and human retroviruses Abstract HIV V118I;Y318F 50;67 55;72 RT 12 14 17209775 Resistance mutational analysis of HIV type 1 subtype C among rural South African drug-naive patients prior to large-scale availability of antiretrovirals. Ninety-five percent of patients had no major mutations in the protease gene, although substitutions M46L (2.5%) and G73S (2.5%), which according to the Stanford Genotypic Resistance Interpretation Algorithm are considered major mutations, were detected. 2006 AIDS research and human retroviruses Abstract HIV G73S;M46L 116;100 120;104 PR 62 70 17211280 Persistence of lamivudine-sensitive HIV-1 quasispecies in the presence of lamivudine in vitro and in vivo. Changes in minority quasispecies of drug-sensitive and drug-resistant HIV-1 variants based on lamivudine and the corresponding lamivudine-resistant viruses carrying the M184I or M184V mutation were investigated using an allele-specific real-time polymerase chain reaction assay. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 169;178 174;183 Pol 246 256 17213262 Prevalence and predictors of antiretroviral drug resistance in newly diagnosed HIV-1 infection. Resistance was scored according to the IAS-USA list (2005) modified to include T215revertants and exclude isolated E44D or V118I and minor protease mutations. 2007 The Journal of antimicrobial chemotherapy Abstract HIV E44D;V118I 115;123 119;128 PR 139 147 1722324 Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. Substitution of cysteine for tyrosine at residue 181 into the wild-type viral genome conferred a similar reduction in susceptibility to nevirapine. 1991 Proc Natl Acad Sci U S A Abstract HIV Y181C 16 52 1722324 Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. These mutants had a substitution of cysteine for the tyrosine at position 181. 1991 Proc Natl Acad Sci U S A Abstract HIV Y181C 36 77 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. Both properties were lost in a mutant Tat protein (F38A) that is deficient in HIV transactivation. 2007 PloS one Abstract HIV F38A 51 55 Tat 38 41 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three resistant viruses. 2007 PLoS medicine Abstract HIV I437T;I437V;K436E 126;126;113 133;133;119 Gag;NC 96;49 99;51 17243183 Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. Saquinavir (SQV), the first antiviral HIV-1 protease (PR) inhibitor approved for AIDS therapy, has been studied in complexes with PR and the variants PR(I) (84V) and PR(V) (82A) containing the single mutations I84V and V82A that provide resistance to all the clinical inhibitors. 2007 Proteins Abstract HIV I84V;V82A 210;219 214;223 PR;PR;PR;PR;PR 44;54;130;150;166 52;56;132;152;168 AIDS 81 85 17262714 Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission. Fading (lack of detection) of K103N was documented in 16 women by 2 years, 43 women by 3 years, and 55 women by 4 and 5 years. 2007 The Journal of infectious diseases Abstract HIV K103N 30 35 17262714 Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission. K103N was detected at 6-8 weeks in 60 (41.7%) of 144 women. 2007 The Journal of infectious diseases Abstract HIV K103N 0 5 17262714 Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission. K103N was detected using the LigAmp assay (assay cutoff, 0.5% K103N). 2007 The Journal of infectious diseases Abstract HIV K103N;K103N 62;0 67;5 17262714 Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission. K103N-containing human immunodeficiency virus (HIV)-1 variants are selected in some women who receive single-dose (SD) nevirapine (NVP) for prevention of HIV-1 mother-infant transmission. 2007 The Journal of infectious diseases Abstract HIV K103N 0 5 17262714 Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission. We examined the persistence of K103N in women who received SD NVP prophylaxis. 2007 The Journal of infectious diseases Abstract HIV K103N 31 36 17267487 A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. A suppressor mutation, encoding a substitution of threonine for alanine at position 105 of CA (A105T), was identified through adaptation of the T54A mutant virus for growth in CEM cells. 2007 Journal of virology Abstract HIV A105T;A105T;T54A 95;50;144 100;87;148 Capsid 91 93 17267487 A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. A105T rescued the impaired single-cycle infectivity and replication defects of both T54A and A92E mutants. 2007 Journal of virology Abstract HIV A92E;T54A;A105T 93;84;0 97;88;5 17267487 A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. Here, we show that substitution of alanine for threonine at position 54 of CA (T54A) also confers HIV-1 resistance to and dependence on CsA. 2007 Journal of virology Abstract HIV T54A;T54A 79;35 83;71 Capsid 75 77 17267487 A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. Interestingly, CsA stimulates the replication of HIV-1 mutants containing either the A92E or G94D substitution in some human cell lines. 2007 Journal of virology Abstract HIV A92E;G94D 85;93 89;97 17267487 A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. Like the previously identified CsA-resistant/dependent mutants, infection by the T54A mutant was stimulated by CsA in a target cell-specific manner. 2007 Journal of virology Abstract HIV T54A 81 85 17267487 A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. Previous studies have identified two mutations, A92E and G94D, in the CypA-binding loop of CA that confer the ability of HIV-1 to replicate in the presence of CsA. 2007 Journal of virology Abstract HIV A92E;G94D 48;57 52;61 Capsid 91 93 17267487 A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. RNA interference-mediated reduction of CypA expression enhanced the permissiveness of HeLa cells to infection by the T54A mutant. 2007 Journal of virology Abstract HIV T54A 117 121 17286555 Characterization of novel non-nucleoside reverse transcriptase (RT) inhibitor resistance mutations at residues 132 and 135 in the 51 kDa subunit of HIV-1 RT. Drug resistance analyses using purified RT, the TyHRT assay and antiviral assays demonstrated that the I132M mutation conferred high-level resistance (>10-fold) to nevirapine and delavirdine and low-level resistance (approximately 2-3-fold) to efavirenz. 2007 The Biochemical journal Abstract HIV I132M 103 108 RT 40 42 17286555 Characterization of novel non-nucleoside reverse transcriptase (RT) inhibitor resistance mutations at residues 132 and 135 in the 51 kDa subunit of HIV-1 RT. The I135A and I135M mutations also conferred low level NNRTI resistance (approximately 2-fold). 2007 The Biochemical journal Abstract HIV I135A;I135M 4;14 9;19 NNRTI 55 60 17287264 Human immunodeficiency virus type 1: resistance to nucleoside analogues and replicative capacity in primary human macrophages. In contrast, mutant viruses exhibited strongly impaired RC relative to the wild type (WT) in macrophages, with the following RC order: WT > two TAMs > four TAMs = M184V > K65R. 2007 Journal of virology Abstract HIV K65R;M184V 171;163 175;168 17287264 Human immunodeficiency virus type 1: resistance to nucleoside analogues and replicative capacity in primary human macrophages. Mutant viruses bearing thymidine analogue mutations (TAMs) or the K65R mutation had similar resistance levels in the two cell types. 2007 Journal of virology Abstract HIV K65R 66 70 17287264 Human immunodeficiency virus type 1: resistance to nucleoside analogues and replicative capacity in primary human macrophages. Strikingly, however, the M184V mutant, although fully resistant to 3TC in P4 cells, maintained some susceptibility to 3TC in macrophages from 8 of 11 donors. 2007 Journal of virology Abstract HIV M184V 25 30 17296739 Interpretation of genotype and pharmacokinetics for resistance to fosamprenavir-ritonavir-based regimens in antiretroviral-experienced patients. The Zephir mutation score included 12 IAS protease mutations associated with poorer virological response: L10I/F/R/V, L33F, M36I, M46I/L, I54L/M/T/V, I62V, L63P, A71I/L/V/T, G73A/C/F/T, V82A/F/S/T, I84V, L90M, and polymorphism mutations I13V, L19I, K55R, and L89M. 2007 Antimicrobial agents and chemotherapy Abstract HIV A71I;A71L;A71T;A71V;G73A;G73C;G73F;G73T;I13V;I54L;I54M;I54T;I54V;I62V;I84V;K55R;L10F;L10I;L10R;L10V;L19I;L33F;L63P;L89M;L90M;M36I;M46I;M46L;V82A;V82F;V82S;V82T 162;162;162;162;174;174;174;174;237;138;138;138;138;150;198;249;106;106;106;106;243;118;156;259;204;124;130;130;186;186;186;186 172;172;172;172;184;184;184;184;241;148;148;148;148;154;202;253;116;116;116;116;247;122;160;263;208;128;136;136;196;196;196;196 PR 42 50 17300185 Molecular dynamics and free energy studies on the wild-type and double mutant HIV-1 protease complexed with amprenavir and two amprenavir-related inhibitors: mechanism for binding and drug resistance. Finally, decomposition analysis of binding free energies and the further structural analysis indicate that the dominating effect of the V82F/I84V double mutation is to distort the geometry of the binding site and hence weaken the interactions of inhibitors preshaped to the wild-type binding site. 2007 Journal of medicinal chemistry Abstract HIV I84V;V82F 141;136 145;140 17300185 Molecular dynamics and free energy studies on the wild-type and double mutant HIV-1 protease complexed with amprenavir and two amprenavir-related inhibitors: mechanism for binding and drug resistance. In the current work, the binding of amprenavir to both of the wild-type and the drug-resistant V82F/I84V mutant of the HIV-1 protease was investigated by molecular dynamics (MD) simulations and was compared to those of two inhibitors in development, TMC126 and TMC114. 2007 Journal of medicinal chemistry Abstract HIV I84V;V82F 100;95 104;99 PR 125 133 17300185 Molecular dynamics and free energy studies on the wild-type and double mutant HIV-1 protease complexed with amprenavir and two amprenavir-related inhibitors: mechanism for binding and drug resistance. The V82F/I84V double mutation is considered as the key residue mutation of the HIV-1 protease drug resistance because it can significantly lower the binding affinity of protease inhibitors in clinical uses. 2007 Journal of medicinal chemistry Abstract HIV I84V;V82F 9;4 13;8 PR;PR 85;169 93;177 17302250 Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients. Mutagenetic trees constructed form this cross-sectional data showed an ordered accumulation of the most prominent CS mutations along two pathways L90M-I84V-P453L and I54-V82-A431V followed by either M46L or L24I. 2006 Antiviral therapy Abstract HIV I84V;L24I;L90M;M46L;P453L;A431V 151;207;146;199;156;174 155;211;150;203;161;179 17302250 Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients. RESULTS: Multiple mutations within the CS p7/p1 and p1/p6-gag accumulated in therapy-experienced isolates (p7/p1: A431V-K436R-I437V and p1/p6-gag: L449F/V-P452S-P453L/A). 2006 Antiviral therapy Abstract HIV L449F;L449V;P452S;P453A;P453L;A431V;I437V;K436R 147;147;155;161;161;114;126;120 154;154;160;168;168;119;131;125 Gag;Gag;Gag;Gag 58;142;55;139 61;145;57;141 17302250 Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients. The analysis of CS and PR mutations in therapy-experienced viruses revealed several positive correlations--A431V with L24I-M46I/L-I54V-V82A; I437V with I54V-V82F/T/S; L449V with I54M/L/S/T/A; and L449F/R452S/P453L: with D30N-I84V--whereas P453L and V82A were negatively correlated. 2006 Antiviral therapy Abstract HIV I54V;L449F;P453L;R452S;V82F;V82S;V82T;A431V;D30N;I437V;I54A;I54L;I54M;I54S;I54T;I54V;I84V;L24I;L449V;M46I;M46L;P453L;V82A;V82A 152;196;208;202;157;157;157;107;220;141;178;178;178;178;178;130;225;118;167;123;123;239;135;249 156;201;213;207;165;165;165;112;224;146;190;190;190;190;190;134;229;122;172;129;129;244;139;253 PR 23 25 17302373 HIV-1 transmission cluster with M41L 'singleton' mutation and decreased transmission of resistance in newly diagnosed Swedish homosexual men. A large transmission cluster with an interesting M41L singleton mutation was also observed. 2006 Antiviral therapy Abstract HIV M41L 49 53 17302373 HIV-1 transmission cluster with M41L 'singleton' mutation and decreased transmission of resistance in newly diagnosed Swedish homosexual men. A transmission cluster involving six patients with a singleton M41L mutation was identified. 2006 Antiviral therapy Abstract HIV M41L 63 67 17302373 HIV-1 transmission cluster with M41L 'singleton' mutation and decreased transmission of resistance in newly diagnosed Swedish homosexual men. The M41L mutation, as well as most other resistance mutations, was stable for many years after transmission and may have been fixated by other putative compensatory mutations. 2006 Antiviral therapy Abstract HIV M41L 4 8 17306618 Genotypic resistance in plasma and peripheral blood lymphocytes in a group of naive HIV-1 patients. In addition, major mutations (D30N, M46I, I50V, I84V) associated with drug resistance in the PR region were only found in PBMCs. 2007 Journal of clinical virology Abstract HIV D30N;I50V;I84V;M46I 30;42;48;36 34;46;52;40 PR 93 95 17306618 Genotypic resistance in plasma and peripheral blood lymphocytes in a group of naive HIV-1 patients. RESULTS: Direct sequencing of DNA provirus disclosed key mutations (such as G190A/S, V106A, K103N and T215F) to RT inhibitors more frequently (7 patients out 31) than in plasma RNA (2 out of 31). 2007 Journal of clinical virology Abstract HIV G190A;G190S;K103N;T215F;V106A 76;76;92;102;85 83;83;97;107;90 RT 112 114 17310813 Impact of HIV-1 reverse transcriptase polymorphism at codons 211 and 228 on virological response to didanosine. A mutation score (M41L+D67N+T69D-K70R +L74V-M 1 84V/I+T21 5Y/F+ K219Q/E+ R211A/D/G/K/S+ L228H/M/R), including two RT polymorphisms not previously described to be associated with ddl resistance (211 and 228) and RT mutations previously described, was associated with a continuum of virological response and increased the predictability of virological response to ddl. 2006 Antiviral therapy Abstract HIV D67N;K219E;K219Q;K70R;L228H;L228M;L228R;L74V;M41L;R211A;R211D;R211G;R211K;R211S;T69D 23;64;64;33;88;88;88;39;18;73;73;73;73;73;28 27;71;71;37;97;97;97;43;22;86;86;86;86;86;32 RT;RT 114;211 116;213 17310813 Impact of HIV-1 reverse transcriptase polymorphism at codons 211 and 228 on virological response to didanosine. RESULTS: Two RT polymorphisms were associated with a reduced virological response to ddl, R211A/D/G/K/S and L228H/M/R, and one with a better virological response: F214L. 2006 Antiviral therapy Abstract HIV F214L;L228H;L228M;L228R;R211A;R211D;R211G;R211K;R211S 163;108;108;108;90;90;90;90;90 168;117;117;117;103;103;103;103;103 RT 13 15 17314158 Relative fitness and replication capacity of a multinucleoside analogue-resistant clinical human immunodeficiency virus type 1 isolate with a deletion of codon 69 in the reverse transcriptase coding region. In the absence of drugs, viral clones containing T69A replicated more efficiently than those having Delta69, but only when patient-derived sequences corresponding to RT residues 248 to 527 were present. 2007 Journal of virology Abstract HIV T69A 49 53 RT 166 168 17314158 Relative fitness and replication capacity of a multinucleoside analogue-resistant clinical human immunodeficiency virus type 1 isolate with a deletion of codon 69 in the reverse transcriptase coding region. In this work, we have measured the in vivo fitness of HIV-1 variants containing a deletion of 3 nucleotides affecting codon 69 (Delta69) of the viral RT as well as the replication capacity (RC) ex vivo of a series of recombinant HIV-1 variants carrying an RT bearing the Delta69 deletion or the T69A mutation in a multidrug-resistant (MDR) sequence background, including the Q151M complex and substitutions M184V, K103N, Y181C, and G190A. 2007 Journal of virology Abstract HIV G190A;K103N;M184V;Q151M;T69A;Y181C 432;414;407;375;295;421 437;419;412;380;299;426 RT;RT 150;256 152;258 17314158 Relative fitness and replication capacity of a multinucleoside analogue-resistant clinical human immunodeficiency virus type 1 isolate with a deletion of codon 69 in the reverse transcriptase coding region. Patient-derived viral clones having RTs with Delta69 together with S163I showed increased RCs under drug pressure. 2007 Journal of virology Abstract HIV S163I 67 72 RT 36 39 17317667 The Werner syndrome helicase is a cofactor for HIV-1 long terminal repeat transactivation and retroviral replication. A dominant-negative helicase-minus mutant, WRN(K577M), inhibits LTR transactivation and HIV-1 replication. 2007 The Journal of biological chemistry Abstract HIV K577M 47 52 LTR 64 67 17317667 The Werner syndrome helicase is a cofactor for HIV-1 long terminal repeat transactivation and retroviral replication. Inhibition of endogenous WRN, through co-expression of WRN(K577M), diminishes recruitment of p300/CREB-binding protein-associated factor (PCAF) and positive transcription elongation factor b (P-TEFb) to Tat/transactivation response-RNA complexes, and immortalized WRN(-/-) WS fibroblasts exhibit comparable defects in recruitment of PCAF and P-TEFb to the HIV-1 LTR. 2007 The Journal of biological chemistry Abstract HIV K577M 59 64 LTR;Tat 362;203 365;206 17324111 Multidrug resistance 1 polymorphisms and trough concentrations of atazanavir and lopinavir in patients with HIV. CONCLUSIONS: These data confirm the higher prevalence of wild-type alleles of the MDR1 gene in African-Americans and the linkage disequilibrium between C3435T and G2677T loci. 2007 Pharmacogenomics Abstract HIV C3435T;G2677T 152;163 158;169 17324111 Multidrug resistance 1 polymorphisms and trough concentrations of atazanavir and lopinavir in patients with HIV. METHODS: In a multicenter study, genotypic analyses at two MDR1 loci, C3435T and G2677T, were performed by a real-time polymerase chain reaction method using DNA from 103 patients categorized as substance users or nonusers on atazanavir or lopinavir as the primary antiretrovirals. 2007 Pharmacogenomics Abstract HIV C3435T;G2677T 70;81 76;87 Pol 119 129 17324111 Multidrug resistance 1 polymorphisms and trough concentrations of atazanavir and lopinavir in patients with HIV. RESULTS: The C/T and G/T alleles at the MDR1 C3435T and G2677T loci were equally frequent in the Caucasian population, but the wild-type alleles were more prevalent in the African-American population (59% homozygous [CC] and 32% heterozygous [CT] for C3435T; 80% homozygous [GG] and 16% heterozygous [GT] for G2677T). 2007 Pharmacogenomics Abstract HIV C3435T;G2677T;G2677T 251;56;309 257;62;315 17324111 Multidrug resistance 1 polymorphisms and trough concentrations of atazanavir and lopinavir in patients with HIV. The frequencies in the Hispanic population were 46% CC and 38% CT for C3435T, and 58% GG and 38% GT for G2677T. 2007 Pharmacogenomics Abstract HIV C3435T;G2677T 70;104 76;110 17324111 Multidrug resistance 1 polymorphisms and trough concentrations of atazanavir and lopinavir in patients with HIV. The T allele at the MDR1 C3435T and G2677T loci was not associated with higher atazanavir or lopinavir trough concentrations. 2007 Pharmacogenomics Abstract HIV G2677T 36 42 17329450 Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene. In this study, we designed oligonucleotide probes to detect the Q151M mutation, associated with phenotypic resistance to zidovudine, didanosine, zalcitabine, and stavudine, and the M184V mutation, associated with phenotypic resistance to lamivudine and emtricitabine, in HIV-2. 2007 Journal of clinical microbiology Abstract HIV M184V;Q151M 181;64 186;69 17329450 Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene. OLA results were compared with sequencing to give high concordances of 98.4% (Q151M) and 97.5% (M184V). 2007 Journal of clinical microbiology Abstract HIV M184V;Q151M 96;78 101;83 17329450 Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene. The overall sensitivity of the assay was 98.8%, with 99.2% for Q151M and 98.4% for M184V. 2007 Journal of clinical microbiology Abstract HIV M184V;Q151M 83;63 88;68 17352764 Cytochrome P450 2B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda. METHODS: The following genotypes were determined in all subjects using polymerase chain reaction-restriction fragment length polymorphism: CYP2B6 G516T, MDR-1 C3435T and G2677T, CYP3A4(*)1B and CYP3A5(*)3. 2007 HIV medicine Abstract HIV G2677T 170 176 Pol 71 81 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. CONCLUSIONS: There is a strong association between H208Y and NRTI experience, particularly in persons with Subtype B harbouring multiple NRTI resistance mutations. 2007 The Journal of antimicrobial chemotherapy Abstract HIV H208Y 51 56 NRTI;NRTI 61;137 65;141 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. H208Y showed a strong association with NRTI experience, which persisted after adjusting for subtype [odds ratio (OR) 19.34; 95% confidence interval (CI) 7.87-47.54; P=0.0001]. 2007 The Journal of antimicrobial chemotherapy Abstract HIV H208Y 0 5 NRTI 39 43 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. H208Y was the most common mutation in both groups (0.2% and 3.8%, respectively) and occurred in 4.5% of treatment-experienced persons with Subtype B, 1.7% of those with Subtype C and 0.7% of those with other non-B subtypes (P=0.001). 2007 The Journal of antimicrobial chemotherapy Abstract HIV H208Y 0 5 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. The median number of TAMs was 4 and 0 in genotypes with and without H208Y, respectively (P=0.0001). 2007 The Journal of antimicrobial chemotherapy Abstract HIV H208Y 68 73 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. The prevalence of H208Y declined over time, being highest in 1998 (9.9%) and lowest in 2003 (0.9%) (P=0.0001). 2007 The Journal of antimicrobial chemotherapy Abstract HIV H208Y 18 23 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. The prevalence of H208Y was highest in genotypes harbouring M184V and the thymidine analogue mutations (TAMs) M41L, D67N, L210W and T215Y. 2007 The Journal of antimicrobial chemotherapy Abstract HIV D67N;H208Y;L210W;M184V;M41L;T215Y 116;18;122;60;108;132 120;23;127;65;114;137 17356061 Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy. These findings indicate an accessory role for H208Y in NRTI resistance. 2007 The Journal of antimicrobial chemotherapy Abstract HIV H208Y 46 51 NRTI 55 59 17360244 Molecular epidemiology and prevalence of drug resistance-associated mutations in newly diagnosed HIV-1 patients in Portugal. Mutations listed by the International AIDS Society-USA were considered, except E44D and V118I. 2007 Infection, genetics and evolution Abstract HIV E44D;V118I 79;88 83;93 AIDS 38 42 17360709 Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication. Genetic analysis revealed that the C-terminal domain of IN is the region responsible for interaction between IN with Imp7, and an IN mutant (K240A,K244A/R263A,K264A) disrupted the Imp7 binding ability of the protein, indicating that both regions ((235)WKGPAKLLWKG and (262)RRKAK) within the C-terminal domain of IN are required for efficient IN/Imp7 interaction. 2007 The Journal of biological chemistry Abstract HIV K240A;K244A;K264A;R263A 141;147;159;153 146;152;164;158 IN;IN;IN;IN;IN 56;109;130;312;342 58;111;132;314;344 17360741 Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations in several gp120 envelope glycoprotein contexts. 2007 Journal of virology Abstract HIV T257S 63 68 Env;gp120 120;114 128;119 17360741 Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. 2007 Journal of virology Abstract HIV S375W 63 68 17360741 Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. The gp120 glycoproteins with the T257S-plus-S375W double mutation (T257S+S375W) have a superior antigenic profile compared to the originally identified single S375W replacement in terms of enhanced recognition by the broadly neutralizing CD4 binding-site antibody b12. 2007 Journal of virology Abstract HIV S375W;S375W;S375W;T257S;T257S 44;73;159;33;67 49;78;164;38;72 gp120 4 9 17360741 Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. The most conformationally constrained T257S+S375W trimeric gp120 proteins were selected for immunogenicity analysis in rabbits and displayed a trend of improvement relative to their wild-type counterparts in terms of eliciting neutralizing antibodies. 2007 Journal of virology Abstract HIV S375W;T257S 44;38 49;43 gp120 59 64 17360741 Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. 2007 Journal of virology Abstract HIV S375W 29 34 gp120 156 161 17360759 Unique thermodynamic response of tipranavir to human immunodeficiency virus type 1 protease drug resistance mutations. Characterization of tipranavir binding to wild-type protease, active site mutants I50V and V82F/I84V, the multidrug-resistant mutant L10I/L33I/M46I/I54V/L63I/V82A/I84V/L90M, and the tipranavir in vitro-selected mutant I13V/V32L/L33F/K45I/V82L/I84V was performed by isothermal titration calorimetry and crystallography. 2007 Journal of virology Abstract HIV I13V;I54V;I84V;I84V;K45I;L10I;L33F;L33I;L63I;L90M;M46I;V32L;V82A;V82L;I50V;I84V;V82F 218;148;163;243;233;133;228;138;153;168;143;223;158;238;82;96;91 222;152;167;247;237;137;232;142;157;172;147;227;162;242;86;100;95 PR 52 60 17367119 Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. Both D30N and N88S confer resistance against NFV. 2007 Journal of medicinal chemistry Abstract HIV D30N;N88S 5;14 9;18 17367119 Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. However, it remains unclear why the nonactive site mutation N88S confers resistance against NFV. 2007 Journal of medicinal chemistry Abstract HIV N88S 60 64 17367119 Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. In contrast, N88S mutants of HIV-1 PRs predominantly emerge in patients in whom NFV treatment has failed and who carry the CRF01_AE virus. 2007 Journal of medicinal chemistry Abstract HIV N88S 13 17 PR 35 38 17367119 Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. Patients in whom NFV treatment has failed predominantly carry D30N mutants of HIV-1 PRs if they have been infected with the subtype B virus. 2007 Journal of medicinal chemistry Abstract HIV D30N 62 66 PR 84 87 17367119 Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. The simulations suggested that despite the nonactive site mutation, N88S causes NFV resistance by reducing interactions between PR and NFV. 2007 Journal of medicinal chemistry Abstract HIV N88S 68 72 PR 128 130 17367119 Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. We also investigated why the emergence rates of D30N and N88S differ between subtype B and CRF01_AE HIV-1. 2007 Journal of medicinal chemistry Abstract HIV D30N;N88S 48;57 52;61 17369083 No response to first-line tenofovir+lamivudine+efavirenz despite optimization according to baseline resistance testing: impact of resistant minority variants on efficacy of low genetic barrier drugs. CASE REPORT: Routine population-based genotypic resistance testing for a newly diagnosed HIV-1 patient revealed the presence of resistance mutations M41L, V179D and T215E within reverse transcriptase and no mutations within protease. 2007 Journal of clinical virology Abstract HIV M41L;T215E;V179D 149;165;155 153;170;160 RT;PR 178;224 199;232 17369083 No response to first-line tenofovir+lamivudine+efavirenz despite optimization according to baseline resistance testing: impact of resistant minority variants on efficacy of low genetic barrier drugs. Retrospective single genome sequencing of the baseline sample revealed the presence of minority viral variants with additional mutations: a mutation conferring resistance to lamivudine (M184IV), a thymidine associated mutation (K219R) and mutations possibly associated with non-nucleoside reverse transcriptase resistance (F227S, M230IV). 2007 Journal of clinical virology Abstract HIV F227S;K219R;M184I;M184V;M230I;M230V 323;228;186;186;330;330 328;233;192;192;336;336 NNRTI 274 310 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. However, despite proper virus release, glycoprotein incorporation and Gag processing, electron microscopy analysis revealed that, in contrast to the E187G mutant, only the E98A particles had aberrant core morphology that resulted in loss of infectivity. 2007 Retrovirology Abstract HIV E187G;E98A 149;172 154;176 Gag 70 73 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. We have studied the effects associated with two single amino acid substitution mutations in HIV-1 capsid (CA), the E98A and E187G. 2007 Retrovirology Abstract HIV E187G;E98A 124;115 129;119 Capsid;Capsid 98;106 104;108 17373782 D- and L-2',3'-didehydro-2',3'-dideoxy-3'-fluoro-carbocyclic nucleosides: synthesis, anti-HIV activity and mechanism of resistance. According to the molecular modeling studies, cross-resistance of D-3'-F-C-d4G (35) to M184V mutant may be caused by the realignment of the primer and template in the HIV-RTM184V interaction, which destabilizes the RT-inhibitor triphosphate complex, resulting in a significant reduction in anti-HIV activity of the D-guanine derivative 35. 2007 Journal of medicinal chemistry Abstract HIV M184V;M184V 86;172 91;177 RT;RT 170;214 172;216 17376023 Atazanavir: simplicity and convenience in different scenarios. Naive patients receiving ATV boosted with ritonavir do not develop PI mutations at failure, whereas unboosted ATV in the same scenario induces the I50L mutation, which does not confer cross-resistance to other PIs. 2007 Expert opinion on pharmacotherapy Abstract HIV I50L 147 151 PI;PI 67;210 69;213 17376903 Human immunodeficiency virus type 1 subtype C Tat fails to induce intracellular calcium flux and induces reduced tumor necrosis factor production from monocytes. In this study, we show that the mutation of a cysteine to a serine at residue 31 of Tat commonly found in subtype C variants significantly inhibits the abilities of the protein to bind to chemokine (C-C motif) receptor 2 (CCR2), induce intracellular calcium flux, stimulate TNF and CCL2 production, and inhibit its chemoattractant properties. 2007 Journal of virology Abstract HIV C31S 46 80 Tat 84 87 17385442 [Prevalence of mutations of resistance to HIV-I reverse transcriptase inhibitors among HIV-infected patients in the Southern Federal District]. The group of patients receiving antiviral treatment was found to have different drug resistance mutations in the HIV-1 pol gene: K70R, M184V, K219Q, T215Y/F, L74V, etc. 2007 Klinicheskaia laboratornaia diagnostika Abstract HIV K219Q;K70R;L74V;M184V;T215F;T215Y 142;129;158;135;149;149 147;133;162;140;156;156 Pol 119 122 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Detection of the integrase mutations A128T and E170G at key positions in the LEDGF/p75-integrase interface provides in vivo evidence for previously reported crystallographic data. 2007 PLoS pathogens Abstract HIV A128T;E170G 37;47 42;52 IN;IN 17;87 26;96 17397894 The role of lysine 186 in HIV-1 integrase multimerization. Co-expression of wild-type IN restored the multimerization defects of IN-K186Q, in both the two-hybrid system and in virions, and also rescued the nuclear targeting defects. 2007 Virology Abstract HIV K186Q 73 78 IN;IN 27;70 29;72 17397894 The role of lysine 186 in HIV-1 integrase multimerization. Virions bearing IN-K186Q were not infectious in a single cycle of replication but when mixed virions containing two different IN mutants were produced, IN-K186Q was capable of complementing the catalytically inactive mutant IN-D116A. 2007 Virology Abstract HIV D116A;K186Q;K186Q 227;19;155 232;24;160 IN;IN;IN;IN 16;126;152;224 18;128;154;226 17397894 The role of lysine 186 in HIV-1 integrase multimerization. We found that alteration of these residues, in particular changing IN lysine residue 186 to glutamate (K186Q), impairs IN oligomerization in the yeast two-hybrid system and decreases oligomeric forms of IN within virions. 2007 Virology Abstract HIV K186E;K186Q 70;103 101;108 IN;IN;IN 67;119;203 69;121;205 17397894 The role of lysine 186 in HIV-1 integrase multimerization. When expressed independently of other viral proteins in human cells, IN-K186Q did not concentrate in the nucleus as did wild-type IN. 2007 Virology Abstract HIV K186Q 72 77 IN;IN 69;130 71;132 17401711 Surveillance of genotypic resistance mutations in chronic HIV-1 treated individuals after completion of the National Access to Antiretroviral Program in Thailand. The reverse transcriptase genes M184V/I (919/1,880; 48.9%) and K103S/H (416/1,880; 22.1%) were the most frequent in nucleoside reverse transcriptase and non-nucleoside reverse transcriptase, respectively. 2007 Infection Abstract HIV K103H;K103S;M184I;M184V 63;63;32;32 70;70;39;39 NNRTI;NRTI;RT 153;116;4 189;148;25 17402200 [Study on the relationship between the polymorphisms and secondary structure of tat exon-1 gene and HIV/ AIDS progress in subtype B' and B'/C]. RESULTS: Many amino acid substitution could be found in the exon 1 of Tat in HIV-1 subtype B' and B'/C recombinant strain infected persons with different disease progression except A58T,none of them showed definitely relationship with HIV viral load and disease progression. 2006 Zhonghua liu xing bing xue za zhi Abstract HIV A58T 181 185 Tat 70 73 17403997 Biochemical studies on the mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to 1-(beta-D-dioxolane)thymine triphosphate. A lower degree of resistance to DOT-TP than to tenofovir diphosphate or carbovir-TP was found for RT containing the K65R mutation. 2007 Antimicrobial agents and chemotherapy Abstract HIV K65R 116 120 RT 98 100 17403997 Biochemical studies on the mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to 1-(beta-D-dioxolane)thymine triphosphate. For non-ATP-dependent discrimination toward DOT-TP, high levels of resistance were found for RT bearing the Q151M mutation with family mutations, while RT bearing only the M184V or the Y115F mutation conferred no resistance to DOT-TP. 2007 Antimicrobial agents and chemotherapy Abstract HIV M184V;Q151M;Y115F 172;108;185 177;113;190 RT;RT 93;152 95;154 17403997 Biochemical studies on the mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to 1-(beta-D-dioxolane)thymine triphosphate. RT containing thymidine analog-associated mutations (TAM) or RT with a T69S-SG insertion in combination with TAM removed 3'-azido-3'-deoxythymidine-5'-monophosphate or tenofovir more efficiently than DOT-monophosphate from chain-terminated DNA primer/template through ATP-mediated pyrophosphorolysis. 2007 Antimicrobial agents and chemotherapy Abstract HIV T69S 71 75 RT;RT 0;61 2;63 17403997 Biochemical studies on the mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to 1-(beta-D-dioxolane)thymine triphosphate. The results suggest that DOT, compared with other approved nucleoside analogs, is overall more resilient to mutations such as TAM, M184V, and K65R, which are commonly found in viruses derived from subjects failing multinucleoside therapy. 2007 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V 142;131 146;136 17411368 Genotypic resistance mutations to antiretroviral drugs in treatment-naive HIV/AIDS patients living in Liaoning Province, China: baseline prevalence and subtype-specific difference. The frequencies of minor mutations to protease inhibitors (PI) were I93L (71.4%), L63P (62.6%), V77I (62.6%), M36I/V (33.0%), A71T/V (22.0%), K20R (6.6%), G16E (6.6%), and L10I (5.5%). 2007 AIDS research and human retroviruses Abstract HIV A71T;A71V;G16E;I93L;K20R;L10I;L63P;M36I;M36V;V77I 126;126;155;68;142;172;82;110;110;96 132;132;159;72;146;176;86;116;116;100 PR;PI 38;59 46;61 17411368 Genotypic resistance mutations to antiretroviral drugs in treatment-naive HIV/AIDS patients living in Liaoning Province, China: baseline prevalence and subtype-specific difference. Three patients (3.3%) had an M46I amino acid substitution in the protease (PR) gene that decreased susceptibility to IDV, RTV, and NFV and one patient (1.1%) had an M184I amino acid substitution in the reverse transcriptase (RT) gene that confers high-level resistance to 3TC and FTC. 2007 AIDS research and human retroviruses Abstract HIV M184I;M46I 165;29 170;33 RT;PR;PR;RT 202;65;75;225 223;73;77;227 17411380 Characterization of an HIV-1 group M variant that is distinct from the known subtypes. Surprisingly, the only regular RT mutation acquired during this period was K70R, which suggests that the genetic background of this variant is perhaps not suitable for the generation of the standard 41L, 67N, and 215Y/F mutations that typically arise during prolonged, nonsuccessful, zidovudine treatment. 2007 AIDS research and human retroviruses Abstract HIV K70R 75 79 RT 31 33 17411383 HIV type 1 drug resistance among naive patients from Venezuela. Our data also suggested that the protease polymorphisms I62T and V77T could be considered as molecular markers of the subtype B local epidemic. 2007 AIDS research and human retroviruses Abstract HIV I62T;V77T 56;65 60;69 PR 33 41 17412697 Mutational and structural studies aimed at characterizing the monomer of HIV-1 protease and its precursor. Assigned backbone chemical shifts were used to elucidate differences in the stability of the PR(T26A) (U(50) = 2.5 M) and (SFNF)PR(D25N) monomers and compared with PR(D25N/T26A) monomer. 2007 The Journal of biological chemistry Abstract HIV D25N;D25N;T26A;T26A 131;167;96;172 135;171;100;176 PR;PR;PR 93;128;164 95;130;166 17412697 Mutational and structural studies aimed at characterizing the monomer of HIV-1 protease and its precursor. Discernible differences in the backbone chemical shifts were observed for N-terminal protease residues 3-6 of (SFNF)PR(D25N) that may relate to the increase in the equilibrium dissociation constant (K(d)) and the very low catalytic activity of the protease prior to its autoprocessing at its N terminus from the Gag-Pol precursor. 2007 The Journal of biological chemistry Abstract HIV D25N 119 123 PR;PR;GagPol;PR 85;248;312;116 93;256;319;118 17412697 Mutational and structural studies aimed at characterizing the monomer of HIV-1 protease and its precursor. Under these conditions, NMR spectra show that the mature protease lacking its terminal beta-sheet residues 1-4 and 96-99 (PR(5-95)) exhibits a stable monomer fold spanning the region 10-90 that is similar to that of the single subunit of the wild-type dimer and the dimer bearing a D25N mutation (PR(D25N)). 2007 The Journal of biological chemistry Abstract HIV D25N;D25N 282;300 286;304 PR;PR;PR 57;122;297 65;124;299 17412697 Mutational and structural studies aimed at characterizing the monomer of HIV-1 protease and its precursor. Urea-induced unfolding monitored both by changes in (1)H-(15)N heteronuclear single quantum correlation spectra and by protein fluorescence indicates that although PR(5-95) monomer displays a transition profile similar to that of the PR(D25N) dimer (50% unfolded (U(50)) = approximately 1.9 M), extending the protease with 4 residues (SFNF) of its N-terminally flanking sequence in the Gag-Pol precursor ((SFNF)PR(D25N)) decreases the stability of the fold (U(50) = approximately 1.5 M). 2007 The Journal of biological chemistry Abstract HIV D25N;D25N 237;414 241;418 PR;GagPol;PR;PR;PR 309;386;164;234;411 317;393;166;236;413 17413687 Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. CONCLUSIONS: The simultaneous presence of K65R and M184V in reverse transcriptase has a negative impact with regard to the efficiency of initiation of (-)ssDNA synthesis and RNA usage, that exceeds the effect of either mutation on its own. 2007 AIDS (London, England) Abstract HIV K65R;M184V 42;51 46;56 RT 60 81 17413687 Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. OBJECTIVES: To determine the underlying biochemical mechanisms responsible for the diminished viral replicative capacity associated with K65R/M184V-containing viruses. 2007 AIDS (London, England) Abstract HIV K65R;M184V 137;142 141;147 17413687 Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. RESULTS: We observed that the K65R/M184V mutations in reverse transcriptase caused reductions in the efficiency of initiation of (-)ssDNA synthesis by increasing pausing at positions +3 and +5 as well as diminished RNA usage. 2007 AIDS (London, England) Abstract HIV K65R;M184V 30;35 34;40 RT 54 75 17413687 Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. These mechanisms, among others, are responsible for the diminished viral replicative capacity observed in tissue culture when K65R/M184V-containing viruses are studied. 2007 AIDS (London, England) Abstract HIV K65R;M184V 126;131 130;136 17413691 Rapid selection of drug-resistant HIV-1 during the first months of suppressive ART in treatment-naive patients. The selection of three key resistance mutations, L90M (protease), K103N and M184V (reverse transcriptase), were measured by allele-specific real-time PCR allowing us to track minority quasispecies with a discriminative power of 0.01-0.2%. 2007 AIDS (London, England) Abstract HIV K103N;L90M;M184V 66;49;76 71;53;81 RT;PR 83;55 104;63 17413698 Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT. K65R became undetectable in two patients, and the development of additional resistance mutations was minimal. 2007 AIDS (London, England) Abstract HIV K65R 0 4 17413698 Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT. K65R was observed in 10 out of 536 treatment-experienced patients entering the study. 2007 AIDS (London, England) Abstract HIV K65R 0 4 17413698 Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT. Over 18 months, no patient developed multinucleoside resistance (Q151M or T69 insertions) and plasma viral loads were stable (median +0.04 log10 copies/ml). 2007 AIDS (London, England) Abstract HIV Q151M 65 71 17413698 Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT. Patients with on-going HIV-1 replication and a K65R mutation in HIV-1 RT were assessed for further development of RT mutations while taking tenofovir disoproxil fumarate and other antiretroviral drugs. 2007 AIDS (London, England) Abstract HIV K65R 47 51 RT;RT 70;114 72;116 17415044 Primary genotypic resistance of HIV-1 to the maturation inhibitor PA-457 in protease inhibitor-experienced patients. Overall, the CA-SP1 cleavage site was highly conserved in PI pre-treated patients and only one patient showed an L231M mutation. 2007 AIDS (London, England) Abstract HIV L231M 113 118 SP1;Capsid;PI 16;13;58 19;15;60 17415044 Primary genotypic resistance of HIV-1 to the maturation inhibitor PA-457 in protease inhibitor-experienced patients. Sequences from 82 protease inhibitors (PI)-experienced patients were analysed for the presence of previously described in-vitro resistance mutations to PA-457 located in the C-terminal capside (H226Y, L231F, L231M) and in the N-terminal SP1 (A1V, A3T, A3V) within the CA-SP1 boundary domain. 2007 AIDS (London, England) Abstract HIV A1V;A3T;A3V;H226Y;L231F;L231M 242;247;252;194;201;208 245;250;255;199;206;213 PR;SP1;SP1;Capsid;PI 18;237;271;268;39 26;240;274;270;41 17416587 Site-specific mutations in HIV-1 gp41 reveal a correlation between HIV-1-mediated bystander apoptosis and fusion/hemifusion. A mutation in the fusion domain of gp41 (V513E) resulted in a fusion-defective Env that failed to induce apoptosis. 2007 The Journal of biological chemistry Abstract HIV V513E 41 46 gp41;Env 35;79 39;82 17416587 Site-specific mutations in HIV-1 gp41 reveal a correlation between HIV-1-mediated bystander apoptosis and fusion/hemifusion. A mutation in the gp41 N-terminal helix (G547D) reduced cell fusion capacity and apoptosis; conversely, an Env mutant with a deletion of the gp41 cytoplasmic tail (Ct Del) enhanced both cell-to-cell fusion and apoptosis. 2007 The Journal of biological chemistry Abstract HIV G547D 41 46 gp41;gp41;Env 18;141;107 22;145;110 17416587 Site-specific mutations in HIV-1 gp41 reveal a correlation between HIV-1-mediated bystander apoptosis and fusion/hemifusion. Most significantly, an Env mutant containing a substitution in the loop region of gp41 (D589L) mediated transfer of lipids (hemifusion) to bystander cells but was defective in cell-to-cell and to a lesser degree virus-to-cell fusion. 2007 The Journal of biological chemistry Abstract HIV D589L 88 93 gp41;Env 82;23 86;26 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. BACKGROUND: We reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251) mutants with a K65R mutation in reverse transcriptase (RT), and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. 2007 Retrovirology Abstract HIV K65R 138 142 RT;RT 155;178 176;180 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. CONCLUSION: This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. 2007 Retrovirology Abstract HIV K70E 86 90 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. 2007 Retrovirology Abstract HIV K65R;K70E 155;84 159;88 RT 89 91 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia. 2007 Retrovirology Abstract HIV K65R 33 37 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. 2007 Retrovirology Abstract HIV K65R;K65R 53;158 57;162 RT 58 60 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be beneficial, particularly when assisted by antiviral immune responses. 2007 Retrovirology Abstract HIV K65R 57 61 17418430 Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy. In 3 of the 28 patients (10.7%), the Q151M complex amino acid substitutions were identified. 2007 Antiviral research Abstract HIV Q151M 37 42 17418430 Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy. TDF-containing regimens reduced HIV-1 viremia in two of the three children carrying the Q151M complex. 2007 Antiviral research Abstract HIV Q151M 88 93 17418430 Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy. These data suggest that the Q151M could be prevalent in pediatric patients with long-term NRTI monotherapy and/or dual NRTI regimens and that HAART regimens containing TDF may be meritorious in such patients. 2007 Antiviral research Abstract HIV Q151M 28 33 NRTI;NRTI 90;119 94;123 17425479 Tipranavir: a new protease inhibitor for the treatment of antiretroviral-experienced HIV-infected patients. The TPV mutation score includes L10V, I13V, K20M/R/V, L33F, E35G, M36I, K43T, M46L, I47V, I54A/M/V, Q58E, H69K, T74P, V82L/T, N83D and I84V. 2007 Expert opinion on pharmacotherapy Abstract HIV E35G;H69K;I13V;I47V;I54A;I54M;I54V;I84V;K20M;K20R;K20V;K43T;L10V;L33F;M36I;M46L;N83D;Q58E;T74P;V82L;V82T 60;106;38;84;90;90;90;135;44;44;44;72;32;54;66;78;126;100;112;118;118 64;110;42;88;98;98;98;139;52;52;52;76;36;58;70;82;130;104;116;124;124 17428874 Mutations in human immunodeficiency virus type 1 RNase H primer grip enhance 3'-azido-3'-deoxythymidine resistance. To test the hypothesis that connection domain mutations enhanced AZT resistance by influencing the RNase H primer grip, we determined the effects of alanine substitutions in RNase H primer grip residues on nucleoside RT inhibitor resistance in the context of a WT, TAM-containing, or K65R-containing polymerase domain. 2007 Journal of virology Abstract HIV K65R 284 288 Pol;RT 300;217 310;219 17434736 Synthesis and evaluation of 2'-substituted cyclobutyl nucleosides and nucleotides as potential anti-HIV agents. Whereas the nucleoside analogs were inactive against HIV-1 in culture, the nucleotide showed good activity not only against wild-type and recombinant HIV RT (IC(50)=4.7, 6.9 microM), but also against the M184I and M184V mutants (IC(50)=6.1, 6.9 microM) in cell-free assays. 2007 Bioorganic & medicinal chemistry letters Abstract HIV M184I;M184V 204;214 209;219 RT 154 156 17436219 Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States. All 4 infants had NNRTI-resistant variants other than the K103N mutation. 2007 The Journal of infectious diseases Abstract HIV K103N 58 63 NNRTI 18 23 17436219 Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States. The fifth infant had the M184V mutation. 2007 The Journal of infectious diseases Abstract HIV M184V 25 30 17436221 Novel mutation of human DNA polymerase gamma associated with mitochondrial toxicity induced by anti-HIV treatment. Culture with stavudine significantly reduced mtDNA levels in patient-derived lymphoblastoid cell lines (LCLs) harboring R964C Pol gamma, compared with those in LCLs harboring wild-type Pol gamma. 2007 The Journal of infectious diseases Abstract HIV R964C 120 125 Pol;Pol 126;185 129;188 17436221 Novel mutation of human DNA polymerase gamma associated with mitochondrial toxicity induced by anti-HIV treatment. In 1 patient with lactic acidosis, a novel homozygous Pol gamma mutation (arginine to cysteine at codon 964 [R964C]) was identified at a site close to polymerase motif B, which is highly conserved among family A polymerases. 2007 The Journal of infectious diseases Abstract HIV R964C;R964C 109;74 114;108 Pol;Pol;Pol 151;212;54 161;223;57 17436221 Novel mutation of human DNA polymerase gamma associated with mitochondrial toxicity induced by anti-HIV treatment. Recombinant R964C Pol gamma showed only 14% activity, compared with that of wild-type Pol gamma. 2007 The Journal of infectious diseases Abstract HIV R964C 12 17 Pol;Pol 18;86 21;89 17441703 Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases. For RT(Leu100Ile), GW420867X does not shift position, in spite of forming different side-chain contacts. 2007 Journal of medicinal chemistry Abstract HIV L100I;R100I;T100I 7;7;7 16;16;16 RT 4 6 17441703 Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases. In a mutated NNRTI pocket, GW420867X either remains in a similar position compared to wild-type (RT(Leu100Ile) and RT(Tyr188Cys)) or rearranges within the pocket (RT(Lys101Glu)). 2007 Journal of medicinal chemistry Abstract HIV K101E;L100I;R100I;R101E;R188C;T100I;T101E;T188C;Y188C 166;100;100;166;118;100;166;118;118 175;109;109;175;127;109;175;127;127 NNRTI;RT;RT;RT 13;97;115;163 18;99;117;165 17442410 Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase. Clonal analysis of six ESS30009 K70E isolates failed to identify double mutants carrying K65R+K70E. 2007 Antiviral research Abstract HIV K65R;K70E 89;94 93;98 17442410 Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase. K65R+K70E phenotypic fold changes for abacavir, lamivudine and tenofovir were comparable to reported values for K65R alone. 2007 Antiviral research Abstract HIV K65R;K70E;K65R 112;5;0 116;9;4 17442410 Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase. Site-directed K70E mutants had a replication capacity of 97+/-29%, but only 2.4+/-0.9% for K65R+K70E and 0.01% for K65R+K70E+M184V mutants. 2007 Antiviral research Abstract HIV K65R;K65R;K70E;K70E;K70E;M184V 91;115;14;96;120;125 95;119;18;100;124;130 17442410 Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase. The K70E mutation in HIV-1 reverse transcriptase was observed in 10% of virologic non-responders of the abacavir/lamivudine/tenofovir arm of ESS30009, alone, or in mixtures with K65R by population sequencing. 2007 Antiviral research Abstract HIV K65R;K70E 178;4 182;8 RT 27 48 17451346 Molecular epidemiology of HIV type 1 in treatment-naive patients in north Ethiopia. One case (1.1%) had the reverse-transcriptase mutation, V75I. 2007 AIDS research and human retroviruses Abstract HIV V75I 56 60 RT 24 45 17451346 Molecular epidemiology of HIV type 1 in treatment-naive patients in north Ethiopia. Two patients (2.2%) had the G190A mutation, which confers resistance to the nonnucleoside reverse transcriptase inhibitor, nevirapine. 2007 AIDS research and human retroviruses Abstract HIV G190A 28 33 NNRTI 76 111 17457088 Lamivudine/abacavir maintains virological superiority over zidovudine/lamivudine and zidovudine/abacavir beyond 5 years in children. Reverse transcriptase resistance mutations emerging on therapy differed between the groups: zidovudine\lamivudine (M41L, D67N, K70R, M184V, L210W, T215Y); zidovudine\abacavir (M41L, D67N, K70R, L210W, T215F/Y, K219Q); lamivudine\abacavir (K65R, L74V, Y115F, M184V). 2007 AIDS (London, England) Abstract HIV D67N;D67N;K219Q;K65R;K70R;K70R;L210W;L210W;L74V;M184V;M184V;M41L;M41L;T215F;T215Y;T215Y;Y115F 121;182;210;239;127;188;140;194;245;133;258;115;176;201;147;201;251 125;186;215;243;131;192;145;199;249;138;263;119;180;208;152;208;256 RT 0 21 17457780 [Epidemiology of primary drug resistance in chronically HIV-infected patients in Nordrhein-Westfalen, Germany, 2001-2005]. After inclusion of mutations E44D and V118I, resistance was identified in 99 patients (11.9%; 95%CI, 9.7-14.1). 2007 Deutsche medizinische Wochenschrift (1946) Abstract HIV E44D;V118I 29;38 33;43 17464964 Synthesis and anti-HIV-1 activity of new MKC-442 analogues with an alkynyl-substituted 6-benzyl group. Moderate activity against Y181C and Y181C + K103N mutated strains was also observed and, in some cases, they were marginally better than those found for MKC-442. 2007 Archiv der Pharmazie Abstract HIV K103N;Y181C;Y181C 44;26;36 49;31;41 17467738 Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development. Our results further indicate that two naturally occurring polymorphic substitutions in subtype F and other non-B HIV proteases, M36I and L89M, may lead to early development of drug resistance in patients infected with non-B HIV subtypes. 2007 Journal of molecular biology Abstract HIV L89M;M36I 137;128 141;132 PR 117 126 17467738 Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development. Our results show that the primary mutation V82A causes the known effect of collapsing the S1/S1' pockets that ultimately lead to the reduced inhibitory effect of TL-3. 2007 Journal of molecular biology Abstract HIV V82A 43 47 17467738 Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development. We have also solved crystal structures of two multi-drug resistant mutant HIV PRs in complex with TL-3, from subtype B (Bmut) carrying the primary mutations V82A and L90M, and from subtype F (Fmut) carrying the primary mutation V82A plus the secondary mutation M36I, at 1.75 A and 2.8 A resolution, respectively. 2007 Journal of molecular biology Abstract HIV L90M;M36I;V82A;V82A 166;261;157;228 170;265;161;232 PR 78 81 17496561 Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. A recombinant virus expressing RT from the original clinical viral sample (Delta70-PRT) exhibited greater fitness than one in which the deletion had been repaired (K70-PRT). 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Delta70-T 75 82 RT 31 33 17496561 Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. Recombinants carrying Delta70-PRT showed greater relative infectivity in the presence of ABC (but not TFV) compared with K70-PRT recombinants. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Delta70-T 21 29 17496561 Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. The Delta70 mutation also increased fitness of Hxb2 wild-type and 74V and Q151M mutants. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 74 79 17496561 Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. The Delta70 mutation increased resistance to lamivudine and emtricitabine alone and in combination with various resistance mutations and augmented resistance to ABC and didanosine when present together with L74V. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L74V 207 211 17496561 Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. The Delta70, L74V, and Q151M mutations were introduced into Hxb2 RT by site-directed mutagenesis and expressed in HIV-1 recombinants. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L74V;Q151M 13;23 17;28 RT 65 67 17496561 Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. We identified a deletion at codon 70 (Delta70) of HIV-1 reverse transcriptase (RT) occurring together with L74V and Q151M mutations in a sample from a tenofovir (TFV)- and abacavir (ABC)-treated patient with extensive prior antiretroviral treatment. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV L74V;Q151M 107;116 111;121 RT;RT 56;79 77;81 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Different patterns of covariation were frequently observed for different mutations at the same position including the RT mutations T69D versus T69N, L74V versus L74I, V75I versus V75M, T215F versus T215Y, and K219Q/E versus K219N/R, and the protease mutations M46I versus M46L, I54V versus I54M/L, and N88D versus N88S. 2007 PLoS computational biology Abstract HIV I54L;I54M;I54V;K219E;K219N;K219Q;K219R;L74I;L74V;M46I;M46L;N88D;N88S;T215F;T215Y;T69D;T69N;V75I;V75M 290;290;278;209;224;209;224;161;149;260;272;302;314;185;198;131;143;167;179 296;296;282;216;231;216;231;165;153;264;276;306;318;190;203;135;147;171;183 PR;RT 241;118 249;120 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Patterns of protease covariation were dominated by the clustering of nelfinavir-associated mutations (D30N and N88D), two main groups of protease inhibitor (PI)-resistance mutations associated either with V82A or L90M, and a tight cluster of mutations associated with decreased susceptibility to amprenavir and the most recently approved PI darunavir. 2007 PLoS computational biology Abstract HIV D30N;L90M;N88D;V82A 102;213;111;205 107;217;115;209 PI;PI;PR;PR 157;338;12;137 159;340;20;145 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Patterns of RT covariation were dominated by the distinct clustering of Type I and Type II thymidine analog mutations and the Q151M-associated mutations. 2007 PLoS computational biology Abstract HIV Q151M 126 131 RT 12 14 17502734 Key amprenavir resistance mutations counteract dramatic efficacy of darunavir in highly experienced patients. Patients harbouring viruses with amprenavir-specific resistance profiles, such as I50V or V32I + I47V, failed on a darunavir/ritonavir-containing regimen. 2007 AIDS (London, England) Abstract HIV I47V;I50V;V32I 97;82;90 101;86;94 17503658 The V118I mutation as a marker of advanced HIV infection and disease progression. BACKGROUND: The V118I mutation is included in the nucleoside analogue mutations (NAMs) set. 2007 Antiviral therapy Abstract HIV V118I 16 21 17503658 The V118I mutation as a marker of advanced HIV infection and disease progression. CONCLUSIONS: The analysis of our observational database suggests that the onset of the V118I mutation after treatment failure is unfavourable for the patient and can be considered a strong marker of disease progression. 2007 Antiviral therapy Abstract HIV V118I 87 92 17503658 The V118I mutation as a marker of advanced HIV infection and disease progression. In univariate analysis, the V118I mutation was significantly associated with a higher HIV RNA level, lower CD4+ T-cell count, Centers for Disease Control and Prevention (CDC) stage C, higher number of pre-GRT regimens and class-wide resistance (CWR) to NRTIs, protease inhibitors and nonnucleoside reverse transcriptase inhibitors. 2007 Antiviral therapy Abstract HIV V118I 28 33 NNRTI;PR;NRTI 284;260;253 319;268;258 17503658 The V118I mutation as a marker of advanced HIV infection and disease progression. RESULTS: Of the 792 patients included, 114 (14.4%) carried the V118I mutation. 2007 Antiviral therapy Abstract HIV V118I 63 68 17503658 The V118I mutation as a marker of advanced HIV infection and disease progression. Using the Cox proportional hazard model and the major clinical, behavioural and laboratory data, the V118I mutation was found to be associated with the endpoint (hazard ratio: 1.93, 95% confidence interval: 1.06-3.50; P=0.031). 2007 Antiviral therapy Abstract HIV V118I 101 106 17503744 Evolution of resistance mutations during low-level viral replication in HIV-1-infected patients treated with zidovudine/lamivudine/abacavir as a first-line regimen. After 54 weeks of treatment with detectable VL, three mutational patterns were observed: Group A (n=4) characterized by M184V without further regimen-associated mutations, group B (n=9) by M184V accompanied by one to three thymidine analogue mutations (TAMs), and group C (n=6) by M184V and four to six TAMs. 2007 Antiviral therapy Abstract HIV M184V;M184V;M184V 120;189;281 125;194;286 17503744 Evolution of resistance mutations during low-level viral replication in HIV-1-infected patients treated with zidovudine/lamivudine/abacavir as a first-line regimen. However, in the majority of patients selection of M184V was associated with accumulation of TAMs at different rates leading to a substantial loss of active NAs, despite continuous virological and immunological benefit when compared with baseline. 2007 Antiviral therapy Abstract HIV M184V 50 55 17503744 Evolution of resistance mutations during low-level viral replication in HIV-1-infected patients treated with zidovudine/lamivudine/abacavir as a first-line regimen. M184V was present in all cases, not followed by further selection of TAMs in a small, unpredictable subgroup of patients. 2007 Antiviral therapy Abstract HIV M184V 0 5 17503757 Genetic diversity and drug resistance mutations in HIV type 1 from untreated patients in Bamako, Mali. After 4 years of ARV use in Mali, two previously untreated individuals (2%; 95% CI: 0.00-4.77%) were found to have resistant viruses, one with a single nucleoside mutation and one with K103N non-nucleoside reverse transcriptase inhibitor resistance mutation. 2007 Antiviral therapy Abstract HIV K103N 185 190 NNRTI 191 227 17506605 Human immunodeficiency virus type 1 drug resistance mutations in peripheral blood mononuclear cell proviral DNA among antiretroviral treatment-naive and treatment-experienced patients from Pune, India. M184V was the most common observed HIVDR mutation. 2007 AIDS research and human retroviruses Abstract HIV M184V 0 5 17507476 Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine. A371V and Q509L also increased cross-resistance with TAMs to lamivudine and abacavir, but not stavudine or didanosine. 2007 Journal of virology Abstract HIV Q509L;A371V 10;0 15;5 17507476 Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine. Because it is not known whether AZT selects for mutations outside of the polymerase domain of RT, we carried out in vitro experiments in which HIV-1(LAI) or AZT-resistant HIV-1(LAI) (M41L/L210W/T215Y) was passaged in MT-2 cells in increasing concentrations of AZT. 2007 Journal of virology Abstract HIV M41L;L210W;T215Y 183;188;194 187;193;199 Pol;RT 73;94 83;96 17507476 Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine. Mutations in the connection and RNase H domains were not selected starting with AZT-resistant virus (M41L/L210W/T215Y). 2007 Journal of virology Abstract HIV M41L;L210W;T215Y 101;106;112 105;111;117 17507476 Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine. The first resistance mutations to appear in HIV-1(LAI) were two polymerase domain thymidine analog mutations (TAMs), D67N and K70R, and two novel mutations, A371V in the connection domain and Q509L in the RNase H domain, that together conferred up to 90-fold AZT resistance. 2007 Journal of virology Abstract HIV A371V;D67N;K70R;Q509L 157;117;126;192 162;121;130;197 Pol 64 74 17507476 Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine. The roles of A371V and Q509L in AZT resistance were confirmed by site-directed mutagenesis: A371V and Q509L together increased AZT resistance approximately 10- to 50-fold in combination with TAMs (M41L/L210W/T215Y or D67N/K70R/T215F) but had a minimal effect without TAMs (1.7-fold). 2007 Journal of virology Abstract HIV M41L;D67N;K70R;L210W;T215F;T215Y;A371V;A371V;Q509L;Q509L 197;217;222;202;227;208;13;92;23;102 201;221;226;207;232;213;18;97;28;107 17507476 Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine. Thereafter, the T215I mutation appeared but was later replaced by T215F, resulting in a large increase in AZT resistance ( approximately 16,000-fold). 2007 Journal of virology Abstract HIV T215F;T215I 66;16 71;21 17509172 Prevalence of primary HIV-1 drug resistance in pregnant women and in newly diagnosed adults at Tijuana General Hospital, Baja California, Mexico. One subject (2.5%) had a major mutation in the reverse transcriptase region (K219Q) conferring zidovudine resistance, one had a minor mutation at V118I (2.5%) and two subjects (5%) had minor mutation (V179D) associated with non-nucleoside reverse transcriptase inhibitor resistance. 2007 International journal of STD & AIDS Abstract HIV K219Q;V118I;V179D 77;146;201 82;151;206 NNRTI;RT 224;47 260;68 17514018 Genetic characterization of HIV-1 strains circulating in Kazakhstan. From these sequences, 47 (58.8%) presented the secondary protease inhibitor mutation V77I that has been linked to a genetic lineage in the FSU epidemic. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V77I 85 89 PR 57 65 17514018 Genetic characterization of HIV-1 strains circulating in Kazakhstan. In addition, most had the other 2 mutations that characterize the "V77I haplotype." All 6 nearly full-length sequences were subtype A and clustered with other FSU strains. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V77I 67 71 17516517 Effective program against mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso. All children had recombinant HIV-1 strain (CRF06_CPX) with: minor PR mutations (M36I, K20I) and RT mutations (R211K). 2007 Journal of medical virology Abstract HIV K20I;M36I;R211K 86;80;110 90;84;115 PR;RT 66;96 68;98 17516517 Effective program against mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso. Among them, two twins had Non-Nucleoside Reverse Transcriptase Inhibitor mutation (Y18CY). 2007 Journal of medical virology Abstract HIV Y18C;Y18Y 83;83 88;88 NNRTI 26 62 17516517 Effective program against mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso. Both mothers acquired a major PR mutation (V8IV), investigated 6 months after a single-dose of Nevirapine. 2007 Journal of medical virology Abstract HIV V8I;V8V 43;43 47;47 PR 30 32 17516531 Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure. Before treatment, 4 of 12 (33.3%) children had primary RTI-resistance mutations, K103N (n = 3, ages 5-7 years) and Y181C (n = 1, age 1 year). 2007 Journal of medical virology Abstract HIV K103N;Y181C 81;115 86;120 RT 55 58 17516531 Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure. In 7 of 12 children, M184V appeared with one thymidine-analogue-associated mutation (TAM) as the first mutation, while the remaining 5 children had only TAMs appearing either individually (n = 2), or as TAMs 1 (M41L, L210W, and T215Y) and 2 (D67N, K70R, and K219Q/E/R) appearing together (n = 3). 2007 Journal of medical virology Abstract HIV D67N;K219E;K219Q;K219R;K70R;L210W;M184V;M41L;T215Y 242;258;258;258;248;217;21;211;228 246;267;267;267;252;222;26;215;233 17516531 Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure. In one child, K103N was found as a minor population (1/5 clones) before treatment and became major (7/7 clones) 8 months after RTI treatment. 2007 Journal of medical virology Abstract HIV K103N 14 19 RT 127 130 17516531 Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure. These results suggest that "vertically transmitted" primary RTI-resistance mutations, K103N and Y181C, can persist over the years even in the absence of drug pressure and impact RTI treatment negatively, and that appearing patterns of RTI-resistance mutations among non-subtype B HIV-1-infected children could possibly be different from those reported in subtype B-infected children. 2007 Journal of medical virology Abstract HIV K103N;Y181C 86;96 91;101 RT;RT;RT 60;178;235 63;181;238 HIV infections 280 294 17516877 Efavirenz. In the case of viral rebound, K103N is the most commonly efavirenz-selected viral mutation. 2007 Expert opinion on pharmacotherapy Abstract HIV K103N 30 35 17522211 Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity of a degradation-resistant APOBEC3G variant. Interestingly, APO3G C97A was highly resistant to Vif-induced degradation even though the two proteins were found to interact in coimmunoprecipitation experiments and exhibited partial colocalization in transfected HeLa cells. 2007 Journal of virology Abstract HIV C97A 21 25 Vif 50 53 17522211 Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity of a degradation-resistant APOBEC3G variant. Surprisingly, encapsidation and antiviral activity of APO3G C97A were both inhibited by Vif despite resistance to degradation. 2007 Journal of virology Abstract HIV C97A 60 64 Vif 88 91 17522211 Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity of a degradation-resistant APOBEC3G variant. We now demonstrate that a multimerization-defective APO3G variant (APO3G C97A) is able to assemble into RNase-sensitive high-molecular-mass (HMM) complexes, suggesting that homo-multimerization of APO3G and assembly into HMM complexes are unrelated RNA-dependent processes. 2007 Journal of virology Abstract HIV C97A 73 77 17522223 Identification of the optimal DC-SIGN binding site on human immunodeficiency virus type 1 gp120. The analysis of multiple mutant forms of the 2G12 epitope revealed one triple glycosylation mutant form, termed 134mut (carrying N293Q, N382Q, and N388Q mutations), that exhibited a significant increase in sensitivity to both mannan competition and endoglycosidase H digestion compared to that of the 124mut form (carrying N293Q, N328Q, and N388Q mutations) and wild-type gp120 in a DC-SIGN binding assay. 2007 Journal of virology Abstract HIV N293Q;N293Q;N328Q;N382Q;N388Q;N388Q 129;323;330;136;147;341 134;328;335;141;152;346 gp120 372 377 17524421 Computational characterization of structural role of the non-active site mutation M36I of human immunodeficiency virus type 1 protease. Here, we performed molecular dynamics (MD) simulations of M36I protease in complex with nelfinavir and revealed the influence of the M36I mutation. 2007 Journal of molecular biology Abstract HIV M36I;M36I 58;133 62;137 PR 63 71 17524421 Computational characterization of structural role of the non-active site mutation M36I of human immunodeficiency virus type 1 protease. However, since the 36th residue is located at a non-active site of the protease and has no direct interaction with any ligands, the structural role of M36I remains unclear. 2007 Journal of molecular biology Abstract HIV M36I 151 155 PR 71 79 17524421 Computational characterization of structural role of the non-active site mutation M36I of human immunodeficiency virus type 1 protease. M36I is the most frequently observed polymorphism in non-subtype B HIV-1 proteases. 2007 Journal of molecular biology Abstract HIV M36I 0 4 PR 73 82 17524421 Computational characterization of structural role of the non-active site mutation M36I of human immunodeficiency virus type 1 protease. The reason for the rare emergence of D30N variants in non-subtype B HIV-1 proteases was also clarified from our computational analysis. 2007 Journal of molecular biology Abstract HIV D30N 37 41 PR 74 83 17524421 Computational characterization of structural role of the non-active site mutation M36I of human immunodeficiency virus type 1 protease. The results show that M36I regulates the size of the binding cavity of the protease. 2007 Journal of molecular biology Abstract HIV M36I 22 26 PR 75 83 17525470 The disulfide loop of gp41 is critical to the furin recognition site of HIV gp160. Based on a luciferase-reporter entry assay, mutants gp41-CC/AA (C598A/C604A) and gp41-Delta (deletion of residues 596-606) result in a nonfunctional envelope protein. 2007 Protein science Abstract HIV C598A;C604A 64;70 69;75 Env;gp41;gp41 149;52;81 157;56;85 17526486 Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. Consistent with this idea, a representative mutation, L537A/W666A, led to an approximately 80% reduction in lipophilic fluorescent dye transfer between gp120-gp41-expressing cells and receptor-expressing targets, indicating a block prior to the lipid-mixing phase. 2007 The Journal of biological chemistry Abstract HIV L537A;W666A 54;60 59;65 gp120;gp41 152;158 157;162 17526486 Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. Simultaneous Ala substitution of Leu(537) with Trp(666), Trp(672), Phe(673), or Ile(675) abolished entry with 50-80% reductions in cell-cell fusion. 2007 The Journal of biological chemistry Abstract HIV L537A 13 41 17526486 Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. The L537A polar segment mutation led to the loss of gp120 from the gp120-gp41 complex, reduced entry by approximately 10-fold, but did not affect cell-cell fusion. 2007 The Journal of biological chemistry Abstract HIV L537A 4 9 gp120;gp120;gp41 52;67;73 57;72;77 17526486 Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. The L537A/W666A double mutation increased the chymotrypsin sensitivity of the polar segment in a trimer of hairpins model, comprising the 6HB core, the polar segment, and MPR linked N-terminally to maltose-binding protein. 2007 The Journal of biological chemistry Abstract HIV L537A;W666A 4;10 9;15 17530993 Emergence of NNRTI drug resistance mutations after single-dose nevirapine exposure in HIV type 1 subtype C-infected infants in India. K103N, one of the most common mutations, was not observed in any of the samples. 2007 AIDS research and human retroviruses Abstract HIV K103N 0 5 17532005 Mutations in capsid major homology region affect assembly and membrane affinity of HIV-1 Gag. However, K158A bound to detergent-resistant raft-like membrane; this was accompanied by noticeably improved VLP production following MA removal. 2007 Journal of molecular biology Abstract HIV K158A 9 14 Matrix 133 135 17532005 Mutations in capsid major homology region affect assembly and membrane affinity of HIV-1 Gag. The membrane-binding capacity of the K158A, F168A, and E175A Gag proteins increased sharply upon removal of the MA globular domain. 2007 Journal of molecular biology Abstract HIV E175A;F168A;K158A 55;44;37 60;49;42 Gag;Matrix 61;112 64;114 17532005 Mutations in capsid major homology region affect assembly and membrane affinity of HIV-1 Gag. While demonstrating improved multimerization capability, the two MA-deleted versions of F168A and E175A did not show marked improvement in VLP production, presumably due to a defect in association with the raft-like membrane domain. 2007 Journal of molecular biology Abstract HIV E175A;F168A 98;88 103;93 Matrix 65 67 17532359 Substitution of alanine for tyrosine-64 in the fingers subdomain of M-MuLV reverse transcriptase impairs strand displacement synthesis and blocks viral replication in vivo. However, substitution of Tyr-64 with phenylalanine and a variety of substitutions at position Leu-99 had no specific effect on displacement synthesis. 2007 Virology Abstract HIV Y64F 25 50 17532359 Substitution of alanine for tyrosine-64 in the fingers subdomain of M-MuLV reverse transcriptase impairs strand displacement synthesis and blocks viral replication in vivo. In vitro assays comparing non-displacement versus displacement synthesis revealed that substitution of alanine at Tyr-64 generated a reverse transcriptase that was impaired in its capacity to carry out DNA and RNA displacement synthesis without affecting polymerase processivity or RNase H activity. 2007 Virology Abstract HIV A64Y 103 120 RT;Pol 133;255 154;265 17532359 Substitution of alanine for tyrosine-64 in the fingers subdomain of M-MuLV reverse transcriptase impairs strand displacement synthesis and blocks viral replication in vivo. The Y64A substitution prevented viral replication in vivo, and Y64A virus generated reduced levels of reverse transcription intermediates at all steps beyond the synthesis of minus strong stop DNA. 2007 Virology Abstract HIV Y64A;Y64A 4;63 8;67 RT 102 123 17537865 X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir. In these two complexes, atazanavir adopts distinct bound conformations in response to the V82F substitution, which may explain why this substitution, at least in isolation, has yet to be selected in vitro or in the clinic. 2007 Journal of virology Abstract HIV V82F 90 94 17537865 X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir. This work describes the X-ray crystal structures of complexes of atazanavir with two HIV-1 protease variants, namely, (i) an enzyme optimized for resistance to autolysis and oxidation, referred to as the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant of the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors, referred to as the inhibitor-resistant mutant. 2007 Journal of virology Abstract HIV I84V;L90M;M46I;V82F 260;265;250;255 264;269;254;259 PR;PR 91;337 99;345 17538883 Evolution of HIV-1 in an HLA-B*57-positive patient during virologic escape. This escape was associated with the development of mutations in 2 HLA-B*57-restricted CD8(+) T cell Gag epitopes, reversion of the drug-resistance mutation M184V, and reversion of a novel polymorphism in Vpu. 2007 The Journal of infectious diseases Abstract HIV M184V 156 161 Vpu;Gag 204;100 207;103 17542150 Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of nucleoside-resistant HIV infection. ATC retains substantial in vitro activity against HIV-1 containing many mutations associated with nucleoside reverse transcriptase inhibitor resistance, showing a less than twofold reduction in susceptibility in the presence of either up to five thymidine analogue mutations or the M184V mutation. 2007 Antiviral chemistry & chemotherapy Abstract HIV M184V 282 287 NRTI 98 130 17542153 Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine as an anti-HIV agent. However, both the K65R and Q151M mutations show decreased excision, which would confer greater stability on the terminated primer. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;Q151M 18;27 22;32 17542153 Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine as an anti-HIV agent. Little or no resistance was observed with the enzymes harbouring mutations resistant to lamivudine (M184V) and non-nucleoside RT inhibitors (K103N). 2007 Antiviral chemistry & chemotherapy Abstract HIV K103N;M184V 141;100 146;105 RT 126 128 17542153 Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine as an anti-HIV agent. RTs containing the D67N/K70R/T215Y/K219Q or T695-SS/T215Y mutations show enhanced removal of DOT-MP from terminated primer as well as approximately four-fold decreased binding/incorporation. 2007 Antiviral chemistry & chemotherapy Abstract HIV D67N;K219Q;K70R;T215Y;T215Y 19;35;24;29;52 23;40;28;34;57 RT 0 3 17542153 Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine as an anti-HIV agent. The Q151M and K65R mutations appear to cause decreased inhibition by DOT-TP. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;Q151M 14;4 18;9 17542154 Kinetics of inhibition of HIV type 1 reverse transcriptase-bearing NRTI-associated mutations by apricitabine triphosphate. However, K65R did not affect rates of primer unblocking for apricitabine-TP. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R 9 13 17542154 Kinetics of inhibition of HIV type 1 reverse transcriptase-bearing NRTI-associated mutations by apricitabine triphosphate. Other mutations such as M184V, L74V and K103N had no effect on the efficiency of chain termination by apricitabine-TP. 2007 Antiviral chemistry & chemotherapy Abstract HIV K103N;L74V;M184V 40;31;24 45;35;29 17542154 Kinetics of inhibition of HIV type 1 reverse transcriptase-bearing NRTI-associated mutations by apricitabine triphosphate. The results showed that the K65R mutation in RT caused reductions in the efficiency of chain-termination of apricitabine-TP by increasing its Ki. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R 28 32 RT 45 47 17542154 Kinetics of inhibition of HIV type 1 reverse transcriptase-bearing NRTI-associated mutations by apricitabine triphosphate. Thus, the mechanism of reduced susceptibility to apricitabine of viruses containing K65R in RT seems to be mediated exclusively through a reduction in binding or incorporation of apricitabine-TP. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R 84 88 RT 92 94 17543558 Insight into analysis of interactions of saquinavir with HIV-1 protease in comparison between the wild-type and G48V and G48V/L90M mutants based on QM and QM/MM calculations. Moreover, the G48V/L90M mutations cause the repositioning of the residues close to residues 48 and 90, at important locations as a part of the flap and catalytic regions, respectively. 2007 Journal of molecular graphics & modelling Abstract HIV G48V;L90M 14;19 18;23 17543558 Insight into analysis of interactions of saquinavir with HIV-1 protease in comparison between the wild-type and G48V and G48V/L90M mutants based on QM and QM/MM calculations. The two most important HIV-1 PR mutants are G48V and G48V/L90M. 2007 Journal of molecular graphics & modelling Abstract HIV G48V;G48V;L90M 44;53;58 48;57;62 PR 29 31 17543558 Insight into analysis of interactions of saquinavir with HIV-1 protease in comparison between the wild-type and G48V and G48V/L90M mutants based on QM and QM/MM calculations. We have found that the interaction of SQV with flap residue 48 of the mutants is significantly perturbed, as shown by the reduced stability of binding between SQV and residue 48 for the G48V and G48V/L90M mutants over the wild-type. 2007 Journal of molecular graphics & modelling Abstract HIV G48V;G48V;L90M 186;195;200 190;199;204 17545713 Drug-resistance surveillance among newly HIV-1 diagnosed individuals in Buenos Aires, Argentina. Phylogenetic analysis revealed evidence for the transmission of the K103N mutation among the drug-naive population. 2007 AIDS (London, England) Abstract HIV K103N 68 73 17545713 Drug-resistance surveillance among newly HIV-1 diagnosed individuals in Buenos Aires, Argentina. RESULTS: We found that 12 (4.2%) of the 284 samples sequenced harbored primary resistance mutations, of which K103N, M41L and V108I were most prevalent. 2007 AIDS (London, England) Abstract HIV K103N;M41L;V108I 110;117;126 115;121;131 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. In contrast, the mutation Q65R, in the leucine-rich domain of Vpr that mediates DCAF1 binding, results in an inactive Vpr devoid of dominant negative behavior. 2007 Virology journal Abstract HIV Q65R 26 30 Vpr;Vpr 62;118 65;121 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. The carboxy-terminal domain Vpr(R80A) mutant, which is able to bind DCAF1, is inactive in checkpoint activation and has dominant-negative character. 2007 Virology journal Abstract HIV R80A 28 37 Vpr 28 31 17562366 Synthesis, anti-HIV activity, and resistance profile of thymidine phosphonomethoxy nucleosides and their bis-isopropyloxymethylcarbonyl (bisPOC) prodrugs. The K65R RT mutant virus was more resistant to the bisPOC prodrugs of 7 and 8 than bisPOC PMPA (tenofovir DF) 1. 2007 Bioorganic & medicinal chemistry Abstract HIV K65R 4 8 RT 9 11 17567542 Mutations at 65 and 70 within the context of a Q151M cluster in human immunodeficiency virus type 1 reverse transcriptase impact the susceptibility to the different nucleoside reverse transcriptase inhibitors in distinct ways. After in vitro culturing in the absence of tenofovir, the virus acquired phenotypic resistance towards tenofovir, associated with the acquisition of K70T and the loss of M184V. 2007 Infection, genetics and evolution Abstract HIV K70T;M184V 149;170 153;175 17567542 Mutations at 65 and 70 within the context of a Q151M cluster in human immunodeficiency virus type 1 reverse transcriptase impact the susceptibility to the different nucleoside reverse transcriptase inhibitors in distinct ways. In vitro culturing in the presence of tenofovir resulted in further enhancement of phenotypic resistance levels towards tenofovir and nucleoside reverse transcriptase inhibitors due to the development of K65R. 2007 Infection, genetics and evolution Abstract HIV K65R 204 208 NRTI 134 166 17567542 Mutations at 65 and 70 within the context of a Q151M cluster in human immunodeficiency virus type 1 reverse transcriptase impact the susceptibility to the different nucleoside reverse transcriptase inhibitors in distinct ways. The original isolate carried the MNR mutations S68G, V75I, F77L, F116Y and Q151M, the lamivudine mutation M184V, the NNRTI mutation K103N and the yet unreported K70S. 2007 Infection, genetics and evolution Abstract HIV F116Y;F77L;K103N;K70S;M184V;Q151M;S68G;V75I 65;59;132;161;106;75;47;53 70;63;137;165;111;80;51;57 NNRTI 117 122 17567789 Sensitive oligonucleotide ligation assay for low-level detection of nevirapine resistance mutations in human immunodeficiency virus type 1 quasispecies. Ten of 19 HIV-1 DNA samples extracted from peripheral blood mononuclear cells had a detectable K103N (0.5 to 44%) or Y181C (0.8 to 92.5%) mutation, but only one plasma HIV-1 RNA sample had a viral population with the Y181C mutation. 2007 Journal of clinical microbiology Abstract HIV K103N;Y181C;Y181C 95;117;217 100;122;222 17567789 Sensitive oligonucleotide ligation assay for low-level detection of nevirapine resistance mutations in human immunodeficiency virus type 1 quasispecies. This modified OLA is now capable of detecting mutants with the K103N or the Y181C mutation present in an HIV-1 population at a frequency of approximately 0.4% and is at least 10- to 30-fold more sensitive than the original protocol. 2007 Journal of clinical microbiology Abstract HIV K103N;Y181C 63;76 68;81 17567789 Sensitive oligonucleotide ligation assay for low-level detection of nevirapine resistance mutations in human immunodeficiency virus type 1 quasispecies. This study has adapted the oligonucleotide ligation assay (OLA) to probe for low-level nevirapine (NVP) resistance mutations K103N and Y181C in the human immunodeficiency virus type 1 (HIV-1) population of infected mother-infant pairs from Uganda. 2007 Journal of clinical microbiology Abstract HIV K103N;Y181C 125;135 130;140 17576848 In vitro selection and characterization of human immunodeficiency virus type 2 with decreased susceptibility to lopinavir. Passage of HIV-2(MS) with increasing concentrations of LPV selected mutations V47A and D17N in the HIV-2 protease gene. 2007 Antimicrobial agents and chemotherapy Abstract HIV D17N;V47A 87;78 91;82 PR 105 113 17576848 In vitro selection and characterization of human immunodeficiency virus type 2 with decreased susceptibility to lopinavir. The introduction of both 17N and 47A either individually or together into HIV-2(ROD) molecular infectious clones showed that the single V47A substitution in HIV-2 resulted in a substantial reduction in susceptibility to LPV. 2007 Antimicrobial agents and chemotherapy Abstract HIV V47A 136 140 17582071 The HBV drug entecavir - effects on HIV-1 replication and resistance. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. 2007 The New England journal of medicine Abstract HIV M184V 159 164 17582071 The HBV drug entecavir - effects on HIV-1 replication and resistance. In vitro experiments showed that M184V confers resistance to entecavir. 2007 The New England journal of medicine Abstract HIV M184V 33 38 17583503 Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. A series of aryl thiotetrazolylacetanilides were synthesized and found to be potent inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. 2007 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 122;128 127;133 RT 148 170 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. CONCLUSION: K65R antagonizes the NRTI monophosphate excision activity of RT containing TAMs. 2007 AIDS (London, England) Abstract HIV K65R 12 16 NRTI;RT 33;73 37;75 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. In addition, the TAMs combination D67N/K70R/T215F/K219Q decreased susceptibility to the L-nucleotide lamivudine by a discrimination mechanism, whereas the M41L/L210W/T215Y combination had little effect on susceptibility to lamivudine. 2007 AIDS (London, England) Abstract HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 34;50;39;160;155;44;166 38;55;43;165;159;49;171 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. METHODS: Steady-state and pre-steady-state kinetic analyses of NRTI triphosphate incorporation and NRTI monophosphate excision by RT containing K65R or TAMs were conducted and complemented by molecular modeling. 2007 AIDS (London, England) Abstract HIV K65R 144 148 NRTI;NRTI;RT 63;99;130 67;103;132 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. OBJECTIVES: The K65R mutation in HIV-1 reverse transcriptase (RT) decreases susceptibility to all approved nucleoside reverse transcriptase inhibitors (NRTI) except zidovudine by selectively decreasing the incorporation of the NRTI triphosphate compared with the natural deoxyribonucleotide triphosphate substrate. 2007 AIDS (London, England) Abstract HIV K65R 16 20 NRTI;RT;NRTI;NRTI;RT 107;39;152;227;62 139;60;156;231;64 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. Recent virology and genetic studies have shown bidirectional antagonism between K65R and TAMs. 2007 AIDS (London, England) Abstract HIV K65R 80 84 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. RESULTS: The addition of K65R to two clinically relevant combinations of TAMs (M41L/L210W/T215Y or D67N/K70R/T215F/K219Q) significantly reduced the recombinant enzymes' ability to excise all chain-terminating NRTI monophosphate. 2007 AIDS (London, England) Abstract HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y;K65R 99;115;104;84;79;109;90;25 103;120;108;89;83;114;95;29 NRTI 209 213 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. TAMs antagonize the ability of K65R RT to discriminate against the nucleotide analog. 2007 AIDS (London, England) Abstract HIV K65R 31 35 RT 36 38 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. Therapies including NRTI that select for both TAMs and K65R may prolong treatment response through the mutually antagonistic interactions between these resistance mutations. 2007 AIDS (London, England) Abstract HIV K65R 55 59 NRTI 20 24 17589186 Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. Transient kinetic analyses showed that TAMs decreased the extent to which RT containing K65R could discriminate against D-nucleotide analogs, but not L-nucleotide analogs, by partly restoring the maximum rate of NRTI triphosphate incorporation. 2007 AIDS (London, England) Abstract HIV K65R 88 92 NRTI;RT 212;74 216;76 17591023 Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1. In the case of TAMs, combinations of > or = 3 mutations (K70G+K219R+L228R+/-V75T) induced PFA resistance and decreased zidovudine resistance 3-13-fold. 2007 Antiviral therapy Abstract HIV K219R;K70G;L228R;V75T 62;57;68;76 67;61;73;80 17591023 Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1. In two patients who received > 12 months of PFA treatment, a novel mutation pattern including K70G, V75T, K219R and L228R emerged. 2007 Antiviral therapy Abstract HIV K219R;K70G;L228R;V75T 106;94;116;100 111;98;121;104 17591023 Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1. In wild-type clones mutations K70G and V75T induced moderate PFA resistance. 2007 Antiviral therapy Abstract HIV K70G;V75T 30;39 34;43 17591023 Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1. Reversion of K70G --> R and K219R --> E in a patient-derived clone confirmed the contribution of individual mutations and the negative association between PFA resistance and zidovudine resistance. 2007 Antiviral therapy Abstract HIV G70R;K219E;K219R;K219R;K70G;K70G;K70R 13;28;28;28;13;13;13 23;39;33;39;17;23;23 17591023 Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1. These mutants exhibited high-level lamivudine resistance (>20-fold) without mutation M184V. 2007 Antiviral therapy Abstract HIV M184V 85 90 17591023 Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1. These viruses had 3-6-fold resistance to PFA, a 2-20-fold decrease in resistance to zidovudine compared to baseline, and 14-39-fold resistance to lamivudine, in the absence of M184V. 2007 Antiviral therapy Abstract HIV M184V 176 181 17596836 Human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns among treatment-naive patients in different stages of infection in Rio de Janeiro, Brazil. This group also presented the only (1.4%) drug-resistance mutation (M184V) among all samples investigated. 2007 Journal of medical virology Abstract HIV M184V 68 73 17597154 The nucleoside analogs 4'C-methyl thymidine and 4'C-ethyl thymidine block DNA synthesis by wild-type HIV-1 RT and excision proficient NRTI resistant RT variants. These compounds are effective against many NRTI drug-resistant RT variants; however, the M184V mutant is relatively resistant. 2007 Journal of molecular biology Abstract HIV M184V 89 94 NRTI;RT 43;63 47;65 17600392 Didanosine enteric-coated capsule: current role in patients with HIV-1 infection. Didanosine may select for resistance mutations that may render the drug inactive against the virus; L74V and K65R remain as the main didanosine-related mutations. 2007 Drugs Abstract HIV K65R;L74V 109;100 113;104 17600392 Didanosine enteric-coated capsule: current role in patients with HIV-1 infection. In vitro, phenotypic susceptibility to didanosine was decreased beyond a defined fold change clinical cut-off (1.7), and it is considered that genotypic resistance exists when five thymidine-associated mutations or four plus M184V are present. 2007 Drugs Abstract HIV M184V 225 230 17604538 HIV type 1 variants with nevirapine resistance mutations are rarely detected in antiretroviral drug-naive African women with subtypes A, C, and D. K103N is frequently detected in HIV-infected women after single dose (SD) nevirapine (NVP). 2007 AIDS research and human retroviruses Abstract HIV K103N 0 5 HIV infections 32 44 17604538 HIV type 1 variants with nevirapine resistance mutations are rarely detected in antiretroviral drug-naive African women with subtypes A, C, and D. K103N-containing variants were also detected more frequently and at higher levels in women with subtype C by the LigAmp assay. 2007 AIDS research and human retroviruses Abstract HIV K103N 0 5 17604538 HIV type 1 variants with nevirapine resistance mutations are rarely detected in antiretroviral drug-naive African women with subtypes A, C, and D. K103N-containing variants were detected more frequently by the ViroSeq HIV-1 Genotyping System in women with subtype C (69.2%) than subtypes A (19.4%, p < 0.0001) or D (36.1%, p < 0.0001). 2007 AIDS research and human retroviruses Abstract HIV K103N 0 5 17604538 HIV type 1 variants with nevirapine resistance mutations are rarely detected in antiretroviral drug-naive African women with subtypes A, C, and D. Only 1/254 samples had an NVP resistance mutation detected with the ViroSeq system, and only 4/236 samples had K103N detected at < 0.5% with the LigAmp assay [2/110 (1.8%) with subtype A, 1/46 (2.2%) with subtype C, and 1/80 (1.3%) with subtype D] (p = 0.92). 2007 AIDS research and human retroviruses Abstract HIV K103N 111 116 17604538 HIV type 1 variants with nevirapine resistance mutations are rarely detected in antiretroviral drug-naive African women with subtypes A, C, and D. We did not detect significant differences in the pre-NVP frequency of NVP resistance mutations or the pre-NVP levels of K103N-containing variants in women with subtypes A, C, and D that explain the dramatic subtype-based differences in emergence of HIV-1 variants with these mutations after SD NVP exposure. 2007 AIDS research and human retroviruses Abstract HIV K103N 120 125 17607772 Detection of drug resistance mutations as a predictor of subsequent virological failure in patients with HIV-1 viral rebounds of less than 1,000 RNA copies/ml. The M184V/I mutation was the most prevalent but in several patients a combination of multiple mutations was detected. 2007 Journal of medical virology Abstract HIV M184I;M184V 4;4 11;11 17609272 Ubiquitination of human immunodeficiency virus type 1 Gag is highly dependent on Gag membrane association. Consistent with this, ubiquitination of a membrane-binding-defective (G2A)Gag mutant was dramatically reduced and the ubiquitination levels of truncated Gag proteins correlated with their abilities to bind to membranes. 2007 Journal of virology Abstract HIV G2A 70 73 Gag;Gag 74;153 77;156 1761538 Kinetic studies of human immunodeficiency virus type 1 protease and its active-site hydrogen bond mutant A28S. Both the wild-type and the mutant A28S enzymes have been overexpressed in Escherichia coli using a chemically synthesized gene and purified for a comparative study in enzyme kinetics. 1991 The Journal of biological chemistry Abstract HIV A28S 34 38 17619115 Polymorphisms and drug resistance analysis of HIV-1 CRF01_AE strains circulating in Fujian Province, China. RESULTS: In comparison with the consensus sequence of B strains, the most common protease polymorphisms in HIV-1 CRF01_AE strains prevailing in Fujian Province, China, were I13V (76.9%), E35D (76.9%), M36I (100%), R41K (98.1%), H69K (90.4%), and L89M (96.2%). 2007 Archives of virology Abstract HIV E35D;H69K;I13V;L89M;M36I;R41K 187;228;173;246;201;214 191;232;177;250;205;218 PR 81 89 17619115 Polymorphisms and drug resistance analysis of HIV-1 CRF01_AE strains circulating in Fujian Province, China. The proportion of substitutions L63P, A71T/V, V77I and I93L in subtype B' sequences was considerably higher than in CRF01_AE viruses, while the proportion of L10I, M36I and K20R/I substitutions in subtype B' sequences was relatively lower than in CRF01_AE strains. 2007 Archives of virology Abstract HIV A71T;A71V;I93L;K20I;K20R;L10I;L63P;M36I;V77I 38;38;55;173;173;158;32;164;46 44;44;59;179;179;162;36;168;50 17626091 DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. The Vpr mutant (Q65R) that was defective for DCAF1 interaction also had a defect in DDB1 binding. 2007 Journal of virology Abstract HIV Q65R 16 20 Vpr 4 7 17636873 A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity. Here, we present the crystal structures at 1.8 A of the free and of the dimannose-bound forms of P51G-m4-CVN, revealing a monomeric structure in which only domain B is bound to dimannose. 2007 Biochemistry Abstract HIV P51G 97 101 17636873 A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity. P51G-m4-CVN binds gp120 with an affinity almost 2 orders of magnitude lower than wt CV-N and is completely inactive against HIV. 2007 Biochemistry Abstract HIV P51G 0 4 gp120 18 23 17636873 A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity. The tight binding to gp120 is recovered in the domain-swapped version of P51G-m4-CVN, prepared under extreme conditions. 2007 Biochemistry Abstract HIV P51G 73 77 gp120 21 26 17636873 A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity. To clarify whether multivalent interactions with gp120 are necessary for the antiviral activity, we engineered a novel mutant, P51G-m4-CVN, in which the binding site on domain A has been knocked out; in addition, a [P51G] mutation prevents the formation of domain-swapped dimers under physiological conditions. 2007 Biochemistry Abstract HIV P51G;P51G 127;216 131;220 gp120 49 54 17640745 NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudine. High-level resistance to nevirapine and moderate level resistance to both stavudine and zidovudine were associated with G190S/A/E substitutions. 2007 Antiviral research Abstract HIV G190A;G190E;G190S 120;120;120 129;129;129 17640745 NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudine. Interestingly, the simultaneous presence of G190S and T215Y was associated with a reduction in the impairment of the G190S-mutated enzyme. 2007 Antiviral research Abstract HIV G190S;G190S;T215Y 44;117;54 49;122;59 17640745 NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudine. On the other hand, G190S was associated with a marked decrease in RT catalytic efficiency, while T215Y showed a more limited effect. 2007 Antiviral research Abstract HIV G190S;T215Y 19;97 24;102 RT 66 68 17640745 NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudine. Recombinant HIV-1 strains carrying G190S/A/E, G190S+T215Y, T215Y and K103N mutations were constructed to evaluate susceptibility to both NNRTIs and nucleoside RT inhibitors (NRTIs). 2007 Antiviral research Abstract HIV G190A;G190E;G190S;G190S;K103N;T215Y;T215Y 35;35;35;46;69;52;59 44;44;44;51;74;57;64 NNRTI;NRTI;RT 137;174;159 143;179;161 17640745 NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudine. Selection of double mutants, with further decrease in NRTI susceptibility, might be favoured by the compensatory effect of T215Y on the reduction of RT catalytic efficiency associated with G190S. 2007 Antiviral research Abstract HIV G190S;T215Y 189;123 194;128 NRTI;RT 54;149 58;151 17640745 NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudine. The simultaneous presence of G190S and T215Y decreased stavudine and zidovudine susceptibility more than T215Y alone. 2007 Antiviral research Abstract HIV G190S;T215Y;T215Y 29;39;105 34;44;110 17642513 Conformational flexibility in the flap domains of ligand-free HIV protease. The mutant HIV PR, which evolved in response to treatment with the potent inhibitor TL-3, contains six point mutations relative to the wild-type enzyme (L24I, M46I, F53L, L63P, V77I, V82A). 2007 Acta crystallographica. Section D, Biological crystallography Abstract HIV F53L;L24I;L63P;M46I;V77I;V82A 165;153;171;159;177;183 169;157;175;163;181;187 PR 15 17 17646201 Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors. For minor darunavir resistance mutations, the rates were V11I 3.3%, V32I 3.9%, L33F 11%, I47V 2.1%, I54L 2.3%, G73S 12.8% and L89V 2.4%. 2007 The Journal of antimicrobial chemotherapy Abstract HIV G73S;I47V;I54L;L33F;L89V;V11I;V32I 111;89;100;79;126;57;68 115;93;104;83;130;61;72 17646201 Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors. The prevalence of major darunavir resistance mutations was I50V 2.1%, I54M 1.3%, L76V 2.7% and I84V 14.5%. 2007 The Journal of antimicrobial chemotherapy Abstract HIV I50V;I54M;I84V;L76V 59;70;95;81 63;74;99;85 17650515 Detection and quantification of minority HIV isolates harbouring the D30N mutation by real-time PCR amplification. METHODS: A real-time PCR assay was optimized for detection of low levels of D30N and tested on in vitro-generated nelfinavir-resistant isolates as well as 10 clinical isolates (which were also characterized by sequencing). 2007 The Journal of antimicrobial chemotherapy Abstract HIV D30N 76 80 17650515 Detection and quantification of minority HIV isolates harbouring the D30N mutation by real-time PCR amplification. Real-time PCR amplification was assessed for its ability to detect the signature mutation for nelfinavir, D30N. 2007 The Journal of antimicrobial chemotherapy Abstract HIV D30N 106 110 17651754 HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions. F130W) have a deleterious effect on viral fitness. 2007 Journal of molecular biology Abstract HIV F130W 0 5 17651754 HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions. Previously, we showed that the effects of F130W are mediated by p51 and can be compensated by mutation T58S. 2007 Journal of molecular biology Abstract HIV F130W;T58S 42;103 47;107 17651754 HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions. Recombinant HIV-1 PRs bearing mutations G94S or T96S showed decreased dimer stability and reduced catalytic efficiency. 2007 Journal of molecular biology Abstract HIV G94S;T96S 40;48 44;52 PR 18 21 17651754 HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions. The PR mutations identified (G94S and T96S) improved the replication capacity of the F130W mutant virus. 2007 Journal of molecular biology Abstract HIV F130W;G94S;T96S 85;29;38 90;34;42 PR 4 6 17651754 HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions. While studying the dynamics of emergence of the compensatory mutation, we observed that mutations in the viral PR-coding region were selected in HIV clones containing the RT substitution F130W, before the imposition of T58S/F130W mutations. 2007 Journal of molecular biology Abstract HIV F130W;F130W;T58S 224;187;219 229;192;223 PR;RT 111;171 113;173 17656588 Mutations that mimic phosphorylation of the HIV-1 matrix protein do not perturb the myristyl switch. We have prepared and studied a series of HIV-1 MA mutants containing Ser-to-Asp substitutions designed to mimic phosphorylation, including substitutions in regions of the protein involved in protein-protein interactions and known to influence the myristyl switch (S6D, S9D, S67D, S72D, S6D/S9D, and S67D/S72D). 2007 Protein science Abstract HIV S67D;S67D;S72D;S72D 274;299;280;304 278;303;284;308 Asp;Matrix 76;47 79;49 17662474 Systematic evaluation of allele-specific real-time PCR for the detection of minor HIV-1 variants with pol and env resistance mutations. The assays achieved sensitivities of <1% for the D30N mutation in HIV-1 PR, M184V and I mutations in RT, and V38A in gp41. 2007 Journal of virological methods Abstract HIV D30N;M184V;V38A 49;76;109 53;81;113 gp41;PR;RT 117;72;101 121;74;103 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Among baseline samples from 154 treatment-experienced patients, 8 had K65R and 44 had L74V/I by population sequencing. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;L74I;L74V 70;86;86 74;92;92 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. BACKGROUND: Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;L74I;L74V 89;79;79 93;85;85 RT 112 133 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Baseline K65R correlated with absence of thymidine analog mutations (TAMs; P = 0.003) and use of ABC or ddI (P = 0.004). 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 9 13 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. CONCLUSIONS: Prior therapy with ABC or ddI can result in a population genotype that shows K65R or L74V/I but does not reveal low-level K65R present in some patients. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;K65R;L74I;L74V 90;135;98;98 94;139;104;104 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Low-level K65R was detected in an additional 11 patients by AS-PCR, 3 of whom subsequently developed full K65R. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;K65R 10;106 14;110 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. METHODS: An allele-specific polymerase chain reaction (AS-PCR) assay was developed to detect K65R with a lower limit of quantitation of 0.5%. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 93 97 Pol 28 38 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Multivariate analyses confirmed that multiple TAMs, K65R, and L74V/I were independent predictors of diminished TDF response. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;L74I;L74V 52;62;62 56;68;68 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Patients with full or low-level K65R at baseline or with L74V/I showed a diminished TDF response. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;L74I;L74V 32;57;57 36;63;63 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF). 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 12 16 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. RESULTS: Among baseline plasma samples from 63 treatment-naive patients, no K65R was detected by AS-PCR. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 76 80 17667333 Low-level K65R mutation in HIV-1 reverse transcriptase of treatment-experienced patients exposed to abacavir or didanosine. Subsequent treatment intensification with TDF resulted in a poor virologic response and may result in expansion of the preexisting K65R mutant. 2007 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 131 135 17668043 Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions. 2007 PloS one Abstract HIV M184V 126 131 RT 148 169 17668565 Primary resistance to enfuvirtide (T20) in recently HIV-1 infected, antiretroviral-naive patients from the ANRS Aquitaine Cohort. The first case had an N42D mutation in the HR1 region of the gp41, along with transmitted resistance mutations in the protease (D30N, M361, N88D) and in the RT (M41L, L210W, T215D). 2007 Antiviral therapy Abstract HIV D30N;L210W;M41L;N42D;N88D;T215D 128;167;161;22;140;174 132;172;165;26;144;179 PR;gp41;RT 118;61;157 126;65;159 17668565 Primary resistance to enfuvirtide (T20) in recently HIV-1 infected, antiretroviral-naive patients from the ANRS Aquitaine Cohort. The second case had a G36D HR1 mutation, with no evidence of other drug resistance mutations. 2007 Antiviral therapy Abstract HIV G36D 22 26 17668566 Natural polymorphism of the HIV-1 integrase gene and mutations associated with integrase inhibitor resistance. Of the 42 aa substitutions currently associated with INI resistance, 21 occurred as natural polymorphisms: V72I, L74I, T97A, T112I, A128T, E138K, Q148H, V151I, S153Y/A, M154I, N155H, K156N, E157Q, G163R, V165I, V201I, I203M, T206S, S230N and R263K. 2007 Antiviral therapy Abstract HIV A128T;E138K;E157Q;G163R;I203M;K156N;L74I;M154I;N155H;Q148H;R263K;S153A;S153Y;S230N;T112I;T206S;T97A;V151I;V165I;V201I;V72I 132;139;190;197;218;183;113;169;176;146;242;160;160;232;125;225;119;153;204;211;107 137;144;195;202;223;188;117;174;181;151;247;167;167;237;130;230;123;158;209;216;111 IN 53 56 17669426 Differential interaction of HIV-1 integrase and JPO2 with the C terminus of LEDGF/p75. However, differing mechanisms of binding were suggested by continuing interaction of JPO2 with some LEDGF/p75 mutants (I365A, D366A, F406A) that are totally defective for interaction with HIV-1 integrase. 2007 Journal of molecular biology Abstract HIV D366A;F406A;I365A 126;133;119 131;138;124 IN 194 203 17678469 The reverse transcriptase 67N 70R 215Y genotype is the predominant TAM pathway associated with virologic failure among HIV type 1C-infected adults treated with ZDV/ddI-containing HAART in southern Africa. The mutation T215Y was the first step in the evolution of the 67N 70R 215Y genotype and was followed by mutations K70R and D67N. 2007 AIDS research and human retroviruses Abstract HIV D67N;K70R;T215Y 123;114;13 127;118;18 17678470 Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients. For NNRTI, K103N significantly increased from 21.8% in 1999 to 29.5% in 2005 (p < 0.01). 2007 AIDS research and human retroviruses Abstract HIV K103N 11 16 NNRTI 4 9 17678470 Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients. K65R significantly increased since 1999 (0.8%) to 2003 (7.3%) but declined up to 3.3% in 2005. 2007 AIDS research and human retroviruses Abstract HIV K65R 0 4 17678470 Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients. Mutations T215Y/F, M184V, and M41L were the most frequent for NRTI. 2007 AIDS research and human retroviruses Abstract HIV M184V;M41L;T215F;T215Y 19;30;10;10 24;34;17;17 NRTI 62 66 17678470 Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients. The most frequent PI resistance mutations were L90M (24.3%), V82X (19.9%), M46I/L (19.5%), and I54V (17.1%). 2007 AIDS research and human retroviruses Abstract HIV I54V;L90M;M46I;M46L;V82X 95;47;75;75;61 99;51;81;81;65 PI 18 20 17686836 Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to nonnucleoside inhibitors. H221Y also showed negative correlations with type 2 thymidine analogue mutations (TAM2s); its copresence with the TAM2s was associated with a higher level of zidovudine susceptibility. 2007 Journal of virology Abstract HIV H221Y 0 5 17686836 Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to nonnucleoside inhibitors. Here, we characterize 10 additional mutations (L74V, K101Q, I135M/T, V179I, H221Y, K223E/Q, and L228H/R) in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase which are involved in the regulation of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). 2007 Journal of virology Abstract HIV H221Y;I135M;I135T;K101Q;K223E;K223Q;L228H;L228R;L74V;V179I 76;60;60;53;83;83;96;96;47;69 81;67;67;58;90;90;103;103;51;74 NNRTI;RT;NNRTI 228;152;276 263;173;282 17686836 Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to nonnucleoside inhibitors. In addition, the presence of the I135T polymorphism in NNRTI-naive patients significantly correlated with the appearance of K103N in cases of NNRTI failure, suggesting that I135T may represent a crucial determinant of NNRTI resistance evolution. 2007 Journal of virology Abstract HIV I135T;I135T;K103N 33;173;124 38;178;129 NNRTI;NNRTI;NNRTI 55;142;218 60;147;223 17686836 Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to nonnucleoside inhibitors. In particular, L74V and H221Y, positively correlated with Y181C, were associated with an increase in Y181C-mediated resistance to nevirapine, while I135M/T mutations, positively correlated with K103N, were associated with an increase in K103N-mediated resistance to efavirenz. 2007 Journal of virology Abstract HIV H221Y;I135M;I135T;K103N;K103N;L74V;Y181C;Y181C 24;148;148;194;237;15;58;101 29;155;155;199;242;19;63;106 17686836 Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to nonnucleoside inhibitors. Molecular dynamics simulations show that I135T can contribute to the stabilization of the K103N-induced closure of the NNRTI binding pocket by reducing the distance and increasing the number of hydrogen bonds between 103N and 188Y. 2007 Journal of virology Abstract HIV I135T;K103N 41;90 46;95 NNRTI 119 124 17692254 [Prevalence of resistance to antiretroviral drugs in Spain]. K103N and Y181C were detected in 24 (67%) and 10 (28%) of the children respectively, while 32 (90%) showed primary mutations to PI. 2007 Anales de pediatria (Barcelona, Spain Abstract HIV Y181C;K103N 10;0 15;5 PI 128 130 17692254 [Prevalence of resistance to antiretroviral drugs in Spain]. NAMs were observed in 94 % of the patients in this group, and one child showed the Q151M mutation. 2007 Anales de pediatria (Barcelona, Spain Abstract HIV Q151M 83 88 17692254 [Prevalence of resistance to antiretroviral drugs in Spain]. NAMs were observed in all patients in this group, and Q151M was found in three children. 2007 Anales de pediatria (Barcelona, Spain Abstract HIV Q151M 54 59 17692254 [Prevalence of resistance to antiretroviral drugs in Spain]. Nucleoside-associated mutations (NAMs) were found in 10 of these patients and the Q151M multiresistance mutation was found in two. 2007 Anales de pediatria (Barcelona, Spain Abstract HIV Q151M 82 87 17692254 [Prevalence of resistance to antiretroviral drugs in Spain]. One child showed three NAMs and another showed Q151M. 2007 Anales de pediatria (Barcelona, Spain Abstract HIV Q151M 47 52 17692254 [Prevalence of resistance to antiretroviral drugs in Spain]. Two children had the K103N mutation. 2007 Anales de pediatria (Barcelona, Spain Abstract HIV K103N 21 26 17696515 Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. Compound 1 had inhibition constants of 17-fold, 8-fold, 3-fold, and 3-fold, respectively, for PR(D30N), PR(I50V), PR(V82A), and PR(I84V) relative to wild type PR. 2007 Journal of medicinal chemistry Abstract HIV D30N;I50V;I84V;V82A 97;107;131;117 101;111;135;121 PR;PR;PR;PR;PR 94;104;114;128;159 96;106;116;130;161 17696515 Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. PR(D30N) and PR(V82A) showed compensating interactions with inhibitor 1 relative to those of PR, while reduced hydrophobic contacts were observed with PR(I50V) and PR(I84V). 2007 Journal of medicinal chemistry Abstract HIV D30N;I50V;I84V;V82A 3;154;167;16 7;158;171;20 PR;PR;PR;PR;PR 0;13;93;151;164 2;15;95;153;166 17696515 Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. The chemically related darunavir had similar relative inhibition, except for PR(D30N), where inhibitor 1 was approximately 3-fold less potent. 2007 Journal of medicinal chemistry Abstract HIV D30N 80 84 PR 77 79 17696515 Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. The potent new antiviral inhibitor GRL-98065 (1) of HIV-1 protease (PR) has been studied with PR variants containing the single mutations D30N, I50V, V82A, and I84V that provide resistance to the major clinical inhibitors. 2007 Journal of medicinal chemistry Abstract HIV D30N;I50V;I84V;V82A 138;144;160;150 142;148;164;154 PR;PR;PR 58;68;94 66;70;96 17705165 Polymorphism and drug selected mutations of reverse transcriptase gene in 102 HIV-1 infected patients living in China. (2) T215Y (23%), M184V (20%), and TAMs (15.4%) in patients receiving d4T + 3TC + EFV. 2007 Journal of medical virology Abstract HIV M184V 17 22 17705165 Polymorphism and drug selected mutations of reverse transcriptase gene in 102 HIV-1 infected patients living in China. An association between H221Y and L228H/R with Y181C was noted. 2007 Journal of medical virology Abstract HIV H221Y;L228H;L228R;Y181C 23;33;33;46 28;40;40;51 17705165 Polymorphism and drug selected mutations of reverse transcriptase gene in 102 HIV-1 infected patients living in China. In treated patients, two patterns of resistance associated mutations (RAMs) were observed: (1) K65R (9.8%), L74V (7.4%), M184V (7.4%), Q151M (5%), and thymidine analogue mutations (TAMs) (9.3%) including T215Y (5.5%), in patients who underwent ddI + d4T + NVP. 2007 Journal of medical virology Abstract HIV L74V;M184V;Q151M;T215Y 108;121;135;204 112;126;140;209 17711379 Utility of repeat genotypic resistance testing and clinical response in patients with three class resistance and virologic treatment failure. On 3C-GRT 2, all patients retained essentially identical mutations, with the exception of the loss of the M184V mutation in 6 patients. 2007 AIDS patient care and STDs Abstract HIV M184V 106 111 17713153 Quadruple nucleoside therapy with zidovudine, lamivudine, abacavir and tenofovir in the treatment of HIV. The presence of L210W, or at least two of the mutations 41L, 67N, 70R, 215F/Y or 219Q/E, at or before baseline seems to be a predictor of non-response, whereas the presence of M184V does not impede virological response and might even be advantageous. 2007 Antiviral therapy Abstract HIV L210W;M184V 16;176 21;181 17713167 Effect of transporter modulation on the emergence of nelfinavir resistance in vitro. Of the 24 isolates passaged without verapamil, 21 carried the D30N mutation at detectable levels. 2007 Antiviral therapy Abstract HIV D30N 62 66 17715137 Changes to the HIV long terminal repeat and to HIV integrase differentially impact HIV integrase assembly, activity, and the binding of strand transfer inhibitors. 3) The strand transfer and inhibitor binding defects of a Q148R mutant are due to a decreased affinity of the complex for magnesium. 2007 The Journal of biological chemistry Abstract HIV Q148R 58 63 17715216 Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. Analysis of heterokaryons between CsA-dependent HeLa-P4 cells and CsA-independent 293T cells indicated that the CsA-dependent infection by A92E and G94D mutants is due to a dominant cellular restriction. 2007 Journal of virology Abstract HIV A92E;G94D 139;148 143;152 17715216 Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. Here, we show that infection by the A92E and G94D mutants is restricted at an early post-entry stage of the HIV-1 life cycle. 2007 Journal of virology Abstract HIV A92E;G94D 36;45 40;49 17715216 Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. Little is known about this cell-dependent phenotype of the A92E and G94D mutants, except that it is not dependent on expression of the host factor TRIM5alpha. 2007 Journal of virology Abstract HIV A92E;G94D 59;68 63;72 17715216 Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. Two CA mutants, A92E and G94D, previously were identified by selection for growth of wild-type HIV-1 in cultures of CD4(+) HeLa cell cultures containing CsA. 2007 Journal of virology Abstract HIV A92E;G94D 16;25 20;29 Capsid 4 6 17724152 Variations in reverse transcriptase and RNase H domain mutations in human immunodeficiency virus type 1 clinical isolates are associated with divergent phenotypic resistance to zidovudine. Although some mutations were also observed in the connection domain, the simultaneous presence of the L74V and M184V mutations was the most significant determinant of phenotypic resistance to ZDV in patients infected with viruses with TAMs. 2007 Antimicrobial agents and chemotherapy Abstract HIV L74V;M184V 102;111 106;116 17725411 Genetic polymorphisms and resistance mutations of HIV type 2 in antiretroviral-naive patients in Burkina Faso. Two samples harbored known resistance mutations: M184V RT mutation in one and Q151M with M184V in the other. 2007 AIDS research and human retroviruses Abstract HIV M184V;M184V;Q151M 49;89;78 54;94;83 RT 55 57 17725415 Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz. In a stepwise, multiple regression analysis, the presence of the K103N mutation at initiation of therapy was associated with VF in both arms (p = 0.001), however, there was a higher incidence of VF in the stavudine arm compared to the emtricitabine arm regardless of the presence or absence of mutations at baseline (p = 0.001). 2007 AIDS research and human retroviruses Abstract HIV K103N 65 70 17725425 Genotypic analysis of the protease and reverse transcriptase of HIV type 1 isolates from recently infected injecting drug users in western China. Compared with subtype B, the CRF07_BC strains had a decreased genetic barrier for the V106M mutation, which is selected by efavirenz and leads to high-level resistance to all present nonnucleoside RT inhibitors. 2007 AIDS research and human retroviruses Abstract HIV V106M 86 91 RT 197 199 17725425 Genotypic analysis of the protease and reverse transcriptase of HIV type 1 isolates from recently infected injecting drug users in western China. It is notable that D60E, L63P and I93L substitutions, which were more common in HIV-1 isolates from PI-treated than untreated patients, were present in most of the isolates. 2007 AIDS research and human retroviruses Abstract HIV D60E;I93L;L63P 19;34;25 23;38;29 PI 100 102 17729291 Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV-1 protease. Although structures have been obtained of complexes between substrate peptide and inactivated (D25N) protease, thermodynamic studies of peptide binding have been challenging due to low affinity. 2008 Proteins Abstract HIV D25N 95 99 PR 101 109 17766368 Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: implications for HIV-1 susceptibility to channel blocking drugs. A18H Vpu TM has an ideal, straight alpha-helix spanning residues 6-27 with an average tilt angle of 41 degrees in C14 phospholipid bicelles, indicating that the tilt angle is increased by 11 degrees compared to that of wild-type Vpu TM. 2007 Protein science Abstract HIV A18H 0 4 Vpu;Vpu 5;229 8;232 17766368 Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: implications for HIV-1 susceptibility to channel blocking drugs. In order to describe the influence of the mutation on the structure and rimantadine susceptibility of Vpu, we determined the structure of A18H Vpu TM, and compared it to those of wild-type Vpu TM and M2 TM. 2007 Protein science Abstract HIV A18H 138 142 Vpu;Vpu;Vpu 102;143;189 105;146;192 17766368 Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: implications for HIV-1 susceptibility to channel blocking drugs. The longer helix formed by the A18H mutation has a larger tilt angle to compensate for the hydrophobic mismatch with the length of the phospholipids in the bilayer. 2007 Protein science Abstract HIV A18H 31 35 17766368 Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: implications for HIV-1 susceptibility to channel blocking drugs. The substitution of alanine at position 18 by a histidine (A18H) has been shown to render HIV-1 infections susceptible to rimantadine, a channel blocker of M2 protein from the influenza virus. 2007 Protein science Abstract HIV A18H;A18H 59;20 63;57 17786489 Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant. In this work, molecular dynamics simulations were performed on a native wild type HIV-1 protease and on the drug-resistant M46I/G51D double mutant. 2007 Journal of molecular modeling Abstract HIV G51D;M46I 128;123 132;127 PR 88 96 17803291 Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity. Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations. 2007 Journal of medicinal chemistry Abstract HIV K103N;L100I;Y181I 72;90;79 77;95;84 RT;RT 45;55 47;58 17803291 Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity. Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring were potent inhibitors of HIV-1 WT and the NNRTI-resistant strains Y181C and K103N-Y181C. 2007 Journal of medicinal chemistry Abstract HIV K103N;Y181C;Y181C 195;185;201 200;190;206 NNRTI 161 166 17827059 Variability of the human immunodeficiency virus type 1 polymerase gene from treatment naive patients in Accra, Ghana. The L10I, L10V, V11I and E35G minor mutations were seen in four patients, while the V179E was observed in a patient with subtype G. 2007 Journal of clinical virology Abstract HIV E35G;L10I;L10V;V11I;V179E 25;4;10;16;84 29;8;14;20;89 17854027 Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. A series of correlated mutations including L10I, M46I, I54V, A71V, G73S, and L90M appeared as a common cluster of amino acid substitutions, associated with failure to lopinavir/ritonavir-based treatments. 2007 Journal of medical virology Abstract HIV A71V;G73S;I54V;L10I;L90M;M46I 61;67;55;43;77;49 65;71;59;47;81;53 17854027 Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. D30N and N88D appeared mostly in patients without previous exposure to protease inhibitors, while K20T was identified as a secondary resistance mutation in those patients. 2007 Journal of medical virology Abstract HIV K20T;N88D;D30N 98;9;0 102;13;4 PR 71 79 17854027 Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. On the other hand, L90M together with L10I, I54V, A71V, G73S, and V82A were selected in protease inhibitor-experienced patients. 2007 Journal of medical virology Abstract HIV A71V;G73S;I54V;L10I;L90M;V82A 50;56;44;38;19;66 54;60;48;42;23;70 PR 88 96 17855539 Suppression of viremia and evolution of human immunodeficiency virus type 1 drug resistance in a macaque model for antiretroviral therapy. K103N resistance-conferring mutations in RT rapidly accumulated in 2/3 infected animals after NNRTI monotherapy and contributed to virologic failure during ART in 1/3 animals. 2007 Journal of virology Abstract HIV K103N 0 5 NNRTI;RT 94;41 99;43 17855574 Molecular characterization of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in Yaounde, Cameroon: evidence of major drug resistance mutations in newly diagnosed patients infected with subtypes other than subtype B. M46L (n = 2), a major resistance mutation associated with resistance to protease inhibitors, was observed in 2/75 (2.6%) group M samples. 2008 Journal of clinical microbiology Abstract HIV M46L 0 4 PR 72 80 17855574 Molecular characterization of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in Yaounde, Cameroon: evidence of major drug resistance mutations in newly diagnosed patients infected with subtypes other than subtype B. Single mutations associated with resistance to nucleoside reverse transcriptase inhibitors (T215Y/F [n = 3]) and nonnucleoside reverse transcriptase inhibitors (V108I [n = 1], L100I [n = 1], and Y181C [n = 2]) were observed in 7 of 75 (9.3%) group M samples. 2008 Journal of clinical microbiology Abstract HIV L100I;T215F;T215Y;V108I;Y181C 176;92;92;161;195 181;100;100;167;200 NNRTI;NRTI 113;47 148;79 17870544 Additional level of information about complex interaction between non-nucleoside inhibitor and HIV-1 reverse transcriptase using biosensor-based thermodynamic analysis. The thermodynamics of the interaction between mutant HIV-1 reverse transcriptase (K103N and Y181C) and a non-nucleoside reverse transcriptase inhibitor (NNRTI), the phenylethylthiazolylurea compound MIV-150, was obtained by determining the temperature dependence of the kinetic rate constants. 2007 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 82;92 88;97 NNRTI;RT;NNRTI 105;59;153 141;80;158 17873990 Genotype testing and antiretroviral resistance profiles from HIV-1 patients experiencing therapeutic failure in northeast Brazil. K65R was detected in 5.9% of the isolates. 2007 The Brazilian journal of infectious diseases Abstract HIV K65R 0 4 17873990 Genotype testing and antiretroviral resistance profiles from HIV-1 patients experiencing therapeutic failure in northeast Brazil. The most frequent mutations were: L90M, M184V and K103N related to PI's, NRTI's and NNRTI's, respectively. 2007 The Brazilian journal of infectious diseases Abstract HIV K103N;L90M;M184V 50;34;40 55;38;45 NNRTI;NRTI;PI 84;73;67 89;77;69 17876005 Novel drug resistance pattern associated with the mutations K70G and M184V in human immunodeficiency virus type 1 reverse transcriptase. We describe an unusual pathway of human immunodeficiency virus type 1 reverse transcriptase resistance during therapy with tenofovir-emtricitabine, characterized initially by the mutations K70E and M184V and later by K70G and M184V, with the two mutations coexisting on the same viral genome. 2007 Antimicrobial agents and chemotherapy Abstract HIV K70E;K70G;M184V;M184V 189;217;198;226 193;221;203;231 RT 70 91 17881449 Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue. Furthermore, the F191H/R changes neither affected the levels of interleukin-2 receptor expression and apoptosis of HIV-1-infected primary T cells nor reduced Nef-mediated induction of NFAT. 2007 Journal of virology Abstract HIV F191H;F191R 17;17 24;24 Nef 158 161 HIV infections 115 129 17881449 Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue. To further evaluate the role of F191 in Nef function and to elucidate the biological relevance of Nef-PAK2 interaction, we performed a comprehensive analysis of HIV-1 Nef mutants carrying F191H and F191R mutations. 2007 Journal of virology Abstract HIV F191H;F191R 188;198 193;203 Nef;Nef;Nef 40;98;167 43;101;170 17881449 Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue. Unexpectedly, the F191H change markedly reduced and the F191R mutation disrupted the ability of Nef to enhance virion infectivity in P4-CCR5 indicator cells but not in TZM-bl cells or peripheral blood mononuclear cells. 2007 Journal of virology Abstract HIV F191H;F191R 18;56 23;61 Nef 96 99 17881449 Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue. We found that the F191H mutation reduces and the F191R mutation disrupts the association of Nef with PAK2. 2007 Journal of virology Abstract HIV F191H;F191R 18;49 23;54 Nef 92 95 17881868 Genotypic resistance mutations in treatment-naive and treatment-experienced patients under widespread use of antiretroviral drugs in Thailand: implications for further epidemiologic surveillance. The most commonly found marker in drug-naive patients was M36I/V/L (n=90, 81.1%), which is a common natural polymorphism among HIV-1 subtype CRF01_AE individuals. 2007 Japanese journal of infectious diseases Abstract HIV M36I;M36L;M36V 58;58;58 66;66;66 17885292 The use of beta-D-2,6-diaminopurine dioxolane with or without mycophenolate mofetil in drug-resistant HIV infection. VR was more frequent with < or = 5 baseline NRTI mutations (P = 0.12) or < 4 thymidine-associated mutations (TAMs) without E44D or V118I (P = 0.08). 2007 AIDS (London, England) Abstract HIV E44D;V118I 123;131 127;136 NRTI 44 48 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. CONCLUSIONS: K103N was detected in some women within 1 year of SD NVP re-exposure, but faded from detection in most women by 3 years after re-exposure. 2007 AIDS (London, England) Abstract HIV K103N 13 18 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. DESIGN: K103N-containing variants were studied in 48 Ugandan women who received SD NVP in the HIVNET 012 trial, and were re-exposed to SD NVP in one (n = 44) or two (n = 4) subsequent pregnancies during a 5-year follow-up study. 2007 AIDS (London, England) Abstract HIV K103N 8 13 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. Detection of K103N by 1 year after SD NVP re-exposure was associated with prior selection of K103N-containing variants and with pre-NVP viral load. 2007 AIDS (London, England) Abstract HIV K103N;K103N 13;93 18;98 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. Detection of K103N was independently associated with detection of K103N 6-8 weeks after the first SD NVP exposure and with pre-NVP viral load. 2007 AIDS (London, England) Abstract HIV K103N;K103N 13;66 18;71 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. K103N was undetectable in 93.2% of evaluable women by 3 years of re-exposure. 2007 AIDS (London, England) Abstract HIV K103N 0 5 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. METHODS: Samples were analyzed using the LigAmp assay (assay cutoff: 0.5% K103N). 2007 AIDS (London, England) Abstract HIV K103N 74 79 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. OBJECTIVES: Use of single dose nevirapine (SD NVP) for prevention of HIV-1 mother-to-child transmission (pMTCT) is associated with selection of K103N-containing HIV variants. 2007 AIDS (London, England) Abstract HIV K103N 144 149 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. Only two of four women who received SD NVP in two pregnancies during the follow-up study had K103N detected after the last SD NVP exposure. 2007 AIDS (London, England) Abstract HIV K103N 93 98 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. RESULTS: Among 44 women who were re-exposed to SD NVP in one subsequent pregnancy, 37.8% had K103N detected within 1 year of SD-NVP re-exposure. 2007 AIDS (London, England) Abstract HIV K103N 93 98 17885298 Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. The portion of women with undetectable K103N by 2 years after SD NVP administration was similar after first versus second use of SD NVP for pMTCT. 2007 AIDS (London, England) Abstract HIV K103N 39 44 17885302 High prevalence of primary lamivudine and nelfinavir resistance in HIV-1-infected pregnant women in the United States, 1998-2004. The prevalence of nelfinavir resistance (D30N) was 6.3%. 2007 AIDS (London, England) Abstract HIV D30N 41 45 17885302 High prevalence of primary lamivudine and nelfinavir resistance in HIV-1-infected pregnant women in the United States, 1998-2004. Using a highly sensitive allele-specific polymerase chain reaction assay we detected the M184V mutation for lamivudine resistance in plasma from 9.4% of HIV-1-infected pregnant women enrolled in the Women and Infant Transmission Study between 1998 and 2004. 2007 AIDS (London, England) Abstract HIV M184V 89 94 Pol 41 51 HIV infections 153 167 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. In contrast, the D51Q mutant was defective both for in vitro capsid assembly and for virus replication in cell culture. 2007 Retrovirology Abstract HIV D51Q 17 21 Capsid 61 67 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. RESULTS: We extended the above investigation by introducing three different D51 substitution mutations (D51N, D51E, and D51Q) into both prokaryotic and eukaryotic expression systems and studied their effects on in vitro capsid assembly and virus infectivity. 2007 Retrovirology Abstract HIV D51E;D51N;D51Q 110;104;120 114;108;124 Capsid 220 226 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Thus, previous substitution mutation of Asp51 to alanine (D51A) has shown to be lethal and that this invariable residue was found essential for tube formation in vitro, virus replication and virus capsid formation. 2007 Retrovirology Abstract HIV D51A;D51A 58;40 62;56 Capsid;Asp 197;40 203;43 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Two substitution mutations (D51E and D51N) had no substantial effect on in vitro capsid assembly, yet they impaired viral infectivity and particle production. 2007 Retrovirology Abstract HIV D51E;D51N 28;37 33;41 Capsid 81 87 17910056 Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism. Peptides corresponding to the TM domain of Vpu (Vpu(1-32)) and mutant peptides (Vpu(1-32)-W23L, Vpu(1-32)-R31V, Vpu(1-32)-S24L) have been synthesized and reconstituted into artificial lipid bilayers. 2008 Proteins Abstract HIV R31V;S24L;W23L 106;122;90 110;126;94 Vpu;Vpu;Vpu;Vpu;Vpu 43;48;80;96;112 46;51;83;99;115 17910056 Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism. Recordings of WT peptide and Vpu(1-32)-W23L indicate Michaelis-Menten behavior when the salt concentration is increased. 2008 Proteins Abstract HIV W23L 39 43 Vpu 29 32 17910056 Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism. Vpu(1-32)-W23L has a considerable flickering pattern in the recordings and longer open times than Vpu(1-32). 2008 Proteins Abstract HIV W23L 10 14 Vpu;Vpu 0;98 3;101 17910056 Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism. Whilst recordings for Vpu(1-32)-R31V are almost indistinguishable from those of the WT peptide, recordings for Vpu(1-32)-S24L do not exhibit any noticeable channel activity. 2008 Proteins Abstract HIV R31V;S24L 32;121 36;125 Vpu;Vpu 22;111 25;114 17910429 Synthesis and biological properties of novel 2-aminopyrimidin-4(3H)-ones highly potent against HIV-1 mutant strains. The new compounds were highly active up to the subnanomolar level against both wt HIV-1 and the Y181C mutant and at the submicromolar to nanomolar range against the K103N and Y188L mutant strains. 2007 Journal of medicinal chemistry Abstract HIV K103N;Y181C;Y188L 165;96;175 170;101;180 17919099 Amino acid conservation in the gp41 transmembrane protein and natural polymorphisms associated with enfuvirtide resistance across HIV-1 variants. In fact, A30V was a signature change in clade G and CRF06_cpx, whereas Q56K/R was a signature change for clades A and J, as well as for CRF04_cpx, CRF09_cpx, CRF11_cpx, and CRF13_cpx. 2007 AIDS research and human retroviruses Abstract HIV A30V;Q56K;Q56R 9;71;71 13;77;77 17919099 Amino acid conservation in the gp41 transmembrane protein and natural polymorphisms associated with enfuvirtide resistance across HIV-1 variants. Some secondary resistance mutations to enfuvirtide were found as natural polymorphisms (A30V and Q56K/R in group M, Q56R and S138A in group O, and S138A in group N). 2007 AIDS research and human retroviruses Abstract HIV A30V;Q56K;Q56R;Q56R;S138A;S138A 88;97;97;116;125;147 93;103;103;120;130;152 17926645 Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). 2007 Antiviral therapy Abstract HIV G190A;G190S;T215Y;V82A;V82F;V82S;V82T 358;358;324;397;397;397;397 365;365;329;407;407;407;407 17926650 HIV genotypic resistance testing to optimize antiretroviral prescribing: is there room for improvement? We analysed the frequency with which patients were prescribed any non-nucleoside reverse transcriptase inhibitor after identification of the K103N mutation in reverse transcriptase and the frequency of prescription of nelfinavir after identification of the D30N mutation in HIV protease; the short-term impact of this action on HIV viral load and CD4+ T-cell count was assessed. 2007 Antiviral therapy Abstract HIV D30N;K103N 257;141 261;146 NNRTI;RT;PR 66;159;278 102;180;286 17931735 The anti-HIV antiviral activity of entecavir: the loss of a trusted friend? Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. 2007 Journal of hepatology Abstract HIV M184V 159 164 17931735 The anti-HIV antiviral activity of entecavir: the loss of a trusted friend? In vitro experiments showed that M184V confers resistance to entecavir. 2007 Journal of hepatology Abstract HIV M184V 33 38 17944683 Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. Although M184I/V may reduce the genetic barrier of ddI for mutations such as K65R and L74V, the lack of re-emergence of M184I/V in the minor quasispecies of most patients who failed ddI suggests that M184I/V was not a preferred route to ddI resistance in our patient population. 2007 HIV medicine Abstract HIV K65R;L74V;M184I;M184I;M184I;M184V;M184V;M184V 77;86;9;120;200;9;120;200 81;90;16;127;207;16;127;207 17944683 Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. CONCLUSIONS: Minor HIV-1 strains may harbour M184I/V in patients failing ddI therapy, despite direct sequencing showing wild-type virus. 2007 HIV medicine Abstract HIV M184I;M184V 45;45 52;52 17944683 Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. M184I/V disappeared in patients in whom 3TC was stopped but ddI continued. 2007 HIV medicine Abstract HIV M184I;M184V 0;0 7;7 17944683 Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. MATERIALS AND METHODS: Fourteen 3TC-experienced patients who, after switching therapy to a ddI regimen, had a new failure without M184I/V in the major viral population were included in the study. 2007 HIV medicine Abstract HIV M184I;M184V 130;130 137;137 17944683 Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. OBJECTIVES: The aim of the study was to investigate the presence of M184I/V in minor HIV-1 populations of patients who failed lamivudine (3TC) and/or didanosine (ddI) treatment. 2007 HIV medicine Abstract HIV M184I;M184V 68;68 75;75 17944683 Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. Ten patients with ddI failure had no M184I/V. 2007 HIV medicine Abstract HIV M184I;M184V 37;37 44;44 17945056 Revertant multiresistant HIV in chronically infected drug naive patients: when baseline resistance testing is not enough. Interestingly, his viral load remained high even in the presence of the M184V mutation. 2007 International journal of STD & AIDS Abstract HIV M184V 72 77 17949071 Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring. A virtual screening protocol has been applied to seek non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) and its K103N mutant. 2007 Journal of chemical information and modeling Abstract HIV K103N 128 133 RT;NNRTI 89;112 110;118 17949071 Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring. The top-ranked molecules obtained from this procedure plus 26 known NNRTIs were then docked into the binding sites of the wild-type reverse transcriptase (HIV-RT) and its K103N variant (K103N-RT) using Glide 3.5. 2007 Journal of chemical information and modeling Abstract HIV K103N;K103N 171;186 176;191 RT;NNRTI;RT;RT 132;68;159;192 153;74;161;194 17955437 Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients. BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. 2007 The Journal of infectious diseases Abstract HIV F214L 60 65 17955437 Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients. CONCLUSIONS: This study provides evidence that the detection of polymorphism F214L is associated with a favorable virological response to TA-based cART. 2007 The Journal of infectious diseases Abstract HIV F214L 77 82 17955437 Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients. However, the virological response to TAs according to the detection of F214L has not been evaluated. 2007 The Journal of infectious diseases Abstract HIV F214L 71 76 17955437 Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients. In ART-experienced patients, results were similar, and larger differences in virological response associated with the detection of 214L versus F were observed in patients with M41L/T215Y and mixed TAM profiles detected before the initiation of cART. 2007 The Journal of infectious diseases Abstract HIV M41L;T215Y 176;181 180;186 17955437 Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients. RESULTS: In ART-naive patients, the prevalence of F214L was 17%. 2007 The Journal of infectious diseases Abstract HIV F214L 50 55 17961108 High frequency of drug resistance mutations in human immunodeficiency virus type 1-infected Korean patients treated with HAART. The most frequently observed mutation was M184V (24.3%, 9/37). 2007 AIDS research and human retroviruses Abstract HIV M184V 42 47 17961120 High prevalence of human immunodeficiency virus type 1 drug resistance mutations in antiretroviral treatment-experienced patients from Pune, India. We report one or more HIV resistance mutations in 81.81% of the 33 antiretroviral treatment-experienced study participants with evidence of virologic failure, with M184V being the most commonly observed resistance mutation (69.7%). 2007 AIDS research and human retroviruses Abstract HIV M184V 164 169 17962184 Pre-steady-state kinetic studies establish entecavir 5'-triphosphate as a substrate for HIV-1 reverse transcriptase. Our results are supported by cell-based assays in primary human lymphocytes that show inhibition of WT HIV-1 replication by ETV and decreased susceptibility of the HIV-1 containing the M184V mutation. 2008 The Journal of biological chemistry Abstract HIV M184V 185 190 17962184 Pre-steady-state kinetic studies establish entecavir 5'-triphosphate as a substrate for HIV-1 reverse transcriptase. This study has important therapeutic implications as it establishes ETV as an inhibitor for HIV-1 RT and illustrates the mechanism of resistance by the M184V mutant. 2008 The Journal of biological chemistry Abstract HIV M184V 152 157 RT 98 100 17962184 Pre-steady-state kinetic studies establish entecavir 5'-triphosphate as a substrate for HIV-1 reverse transcriptase. To investigate this question at a molecular level, kinetic studies were used to examine the interaction of 5'-triphosphate form of ETV with wild type (WT) HIV-1 reverse transcriptase (RT) and the nucleoside reverse transcriptase inhibitor-resistant mutation M184V. 2008 The Journal of biological chemistry Abstract HIV M184V 258 263 NRTI;RT;RT 196;161;184 228;182;186 17962184 Pre-steady-state kinetic studies establish entecavir 5'-triphosphate as a substrate for HIV-1 reverse transcriptase. Using single turnover kinetic assays, we found that HIV-1 WT RT and M184V RT could use the activated ETV triphosphate metabolite as a substrate for incorporation. 2008 The Journal of biological chemistry Abstract HIV M184V 68 73 RT;RT 61;74 63;76 17962868 Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. 2007 The Brazilian journal of infectious diseases Abstract HIV I84V;K219E;K219Q;K70R;L210W;L90M;M41L;T215F;T215Y;V82A;V82F;V82L;V82T 69;112;112;87;93;75;81;100;100;57;57;57;57 73;119;119;91;98;79;85;107;107;67;67;67;67 17962906 Evidence of dual sexual transmission of multi-resistant HIV with two years persistence of resistance to NRTI and NNRTI: a case report. A case report of dual sexual transmission, with secondary transmission from naive to naive patient, of HIV harbouring K103N and L100I mutations, conferring full non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, plus 2 nucleoside analogous reverse transcriptase inhibitor (NRTI) mutations is described. 2008 Infection Abstract HIV K103N;L100I 118;128 123;133 NNRTI;RT;NNRTI;NRTI 161;256;209;289 197;277;214;293 17967907 Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine. First, in combination with M184V, G333D increased the ability of HIV-1 RT to effectively discriminate between the normal substrate dCTP and 3TC-triphosphate. 2008 Antimicrobial agents and chemotherapy Abstract HIV G333D;M184V 34;27 39;32 RT 71 73 17967907 Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine. Our results from steady-state kinetic, pre-steady-state kinetic, and thermodynamic analyses indicate that G333D facilitates dual resistance to AZT and 3TC in two ways. 2008 Antimicrobial agents and chemotherapy Abstract HIV G333D 106 111 17967907 Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine. Second, G333D enhanced the ability of RT containing TAMs and M184V to bind template/primer terminated by AZT-monophosphate (AZT-MP), thereby restoring ATP-mediated excision of AZT-MP under steady-state assay conditions. 2008 Antimicrobial agents and chemotherapy Abstract HIV G333D;M184V 8;61 13;66 RT 38 40 17967907 Mechanisms by which the G333D mutation in human immunodeficiency virus type 1 Reverse transcriptase facilitates dual resistance to zidovudine and lamivudine. To provide insight into the biochemical mechanism(s) involved, we investigated the effect of the G333D mutation in the connection domain of RT on resistance to zidovudine (AZT) and lamivudine (3TC) in enzymes that contain both M184V and thymidine analog mutations (TAMs; M41L, L210W, and T215Y). 2008 Antimicrobial agents and chemotherapy Abstract HIV G333D;L210W;M184V;M41L;T215Y 97;277;227;271;288 102;282;232;275;293 RT 140 142 17967909 Comparative evaluation of the inhibitory activities of a series of pyrimidinedione congeners that inhibit human immunodeficiency virus types 1 and 2. Six molecules exhibited significant inhibition of viruses with the highly problematic nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance engendering amino acid change K103N in the reverse transcriptase. 2008 Antimicrobial agents and chemotherapy Abstract HIV K103N 181 186 NNRTI;RT;NNRTI 86;194;133 121;215;138 17977555 Molecular analysis of the HIV-1 resistance development: enzymatic activities, crystal structures, and thermodynamics of nelfinavir-resistant HIV protease mutants. Crystal structures, molecular dynamics simulations, and calorimetric data for four mutants (D30N, D30N/A71V, D30N/N88D, and D30N/L90M) were used to augment our kinetic data. 2007 Journal of molecular biology Abstract HIV A71V;D30N;D30N;D30N;D30N;L90M;N88D 103;92;98;109;124;129;114 107;96;102;113;128;133;118 17977555 Molecular analysis of the HIV-1 resistance development: enzymatic activities, crystal structures, and thermodynamics of nelfinavir-resistant HIV protease mutants. Here we analyze the proteolytic activities, X-ray structures, and thermodynamics of inhibitor binding to HIV-1 PRs harboring the D30N and L90M mutations alone and in combination with other compensatory mutations. 2007 Journal of molecular biology Abstract HIV D30N;L90M 129;138 133;142 PR 111 114 17977555 Molecular analysis of the HIV-1 resistance development: enzymatic activities, crystal structures, and thermodynamics of nelfinavir-resistant HIV protease mutants. In the PR sequence of viral variants resistant to the PI nelfinavir, the mutations D30N and L90M appear frequently. 2007 Journal of molecular biology Abstract HIV D30N;L90M 83;92 87;96 PI;PR 54;7 56;9 17977555 Molecular analysis of the HIV-1 resistance development: enzymatic activities, crystal structures, and thermodynamics of nelfinavir-resistant HIV protease mutants. The combination of the D30N and L90M mutations significantly increases the enzyme vitality in the presence of nelfinavir, without a dramatic decrease in the catalytic efficiency of the recombinant enzyme. 2007 Journal of molecular biology Abstract HIV D30N;L90M 23;32 27;36 17977962 Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). Among the observed IN mutations, T66I and E92Q substitutions mainly contributed to EVG resistance. 2008 Journal of virology Abstract HIV E92Q;T66I 42;33 46;37 IN 19 21 17981909 A quantum mechanic/molecular mechanic study of the wild-type and N155S mutant HIV-1 integrase complexed with diketo acid. In this study, we use molecular dynamics simulations, within the hybrid quantum mechanics/molecular mechanics (QM/MM) approach, to determine the protein-ligand interaction energy for wild-type and N155S mutant HIV-1 IN, both complexed with a DKA. 2008 Biophysical journal Abstract HIV N155S 197 202 IN 216 218 17981909 A quantum mechanic/molecular mechanic study of the wild-type and N155S mutant HIV-1 integrase complexed with diketo acid. Our calculations show that the binding energy is higher in wild-type than in the N155S mutant, in accordance with the experimental results. 2008 Biophysical journal Abstract HIV N155S 81 86 18003735 Subtype-specific conformational differences within the V3 region of subtype B and subtype C human immunodeficiency virus type 1 Env proteins. A single mutation in V3 (H13R) made this chimeric Env selectively resistant to one group of V3 MAbs, consistent with the mAb binding properties. 2008 Journal of virology Abstract HIV H13R 25 29 Env 50 53 18008248 Improved interpretation of genotypic changes in the HIV-1 reverse transcriptase coding region that determine the virological response to didanosine. The best correlation with response was found with the derived score (M41L x 2) + E44D/A/G + T69D/S/N/A + (L210W x 2) + T215Y or revertants + L228H/R - D123E/N/G/S, by use of which viruses were categorized as being susceptible (score < or =0), as having intermediate resistance (1-3), and as being resistant (> or =4) to didanosine. 2007 The Journal of infectious diseases Abstract HIV D123E;D123G;D123N;D123S;E44A;E44D;E44G;L210W;L228H;L228R;M41L;T215Y;T69A;T69D;T69N;T69S 151;151;151;151;81;81;81;106;141;141;69;119;92;92;92;92 162;162;162;162;89;89;89;112;148;148;74;124;102;102;102;102 18024202 Evolution of the HIV-1 protease region in heavily pretreated HIV-1 infected patients receiving Atazanavir. In two of these subjects new mutations (I54V and A71V) conferring cross-resistance emerged after 3 months of therapy. 2008 Journal of clinical virology Abstract HIV A71V;I54V 49;40 53;45 18024202 Evolution of the HIV-1 protease region in heavily pretreated HIV-1 infected patients receiving Atazanavir. The I50L mutation was evidenced in one subject after 12 months of treatment. 2008 Journal of clinical virology Abstract HIV I50L 4 8 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705-restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1-specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. 2007 The Journal of experimental medicine Abstract HIV L6M 187 190 Gag 103 106 HIV infections 391 408 18025887 High concordance between HIV-1 drug resistance genotypes generated from plasma and dried blood spots in antiretroviral-experienced patients. Discrepancies were mostly caused by mixtures at minor protease positions or unusual amino acid changes, and in only two cases were caused by major protease (M46L) or reverse transcriptase (K103N) mutations absent in DBS sequences. 2007 AIDS (London, England) Abstract HIV K103N;M46L 189;157 194;161 RT;PR;PR 166;54;147 187;62;155 18029175 Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC(50)=2.1 microM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT. 2007 Bioorganic & medicinal chemistry letters Abstract HIV K65R;M184V 211;217 215;222 RT 265 267 18034204 Observational study on HIV-infected subjects failing HAART receiving tenofovir plus didanosine as NRTI backbone. M184V was marginally associated with virologic success (HR: 1.34, 95% CI: 0.94-1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not associated. 2007 Infection Abstract HIV M184V;M184V 100;0 105;5 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Finally, the replication of the Vpr-L23F and Vpr-K27M hCG1-binding deficient mutant viruses was also affected in primary macrophages from some but not all donors. 2007 Retrovirology Abstract HIV K27M;L23F 45;32 53;40 Vpr;Vpr 32;45 35;48 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. However, this localization is not sufficient, since mutations within the C-terminal basic region of Vpr (Vpr-R80A and Vpr-R90K), disrupted the G2-arrest and apoptotic activities without altering NE localization. 2007 Retrovirology Abstract HIV R80A;R90K 105;118 114;126 Vpr;Vpr;Vpr 100;105;118 103;108;121 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Other mutants with substitutions in the first alpha-helix (Vpr-A30L and Vpr-F34I) were similarly distributed between the nucleus and cytoplasm, demonstrating that this helix contains the determinants required for localization of Vpr at the NE. 2007 Retrovirology Abstract HIV A30L;F34I 59;72 68;80 Vpr;Vpr;Vpr 59;72;229 62;75;232 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. RESULTS: In order to define the functional role of Vpr localization at the NE, we have characterized a set of single-point Vpr mutants, and selected two new mutants with substitutions within the first alpha-helix of the protein, Vpr-L23F and Vpr-K27M, that failed to associate with hCG1, but were still able to interact with other known relevant host partners of Vpr. 2007 Retrovirology Abstract HIV K27M;L23F 242;229 250;237 Vpr;Vpr;Vpr;Vpr;Vpr 51;123;229;242;363 54;126;232;245;366 18039922 Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir. By contrast, L76V, a known DRV resistance mutation, was found to decrease the risk of selection of another DRV resistance mutation. 2008 Antimicrobial agents and chemotherapy Abstract HIV L76V 13 17 18039922 Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir. The most common mutations that emerged at rebound included V32I (44%), I54M/L (24%), L33F (25%), I84V (21%), and L89V (12%). 2008 Antimicrobial agents and chemotherapy Abstract HIV I54L;I54M;I84V;L33F;L89V;V32I 71;71;97;85;113;59 77;77;101;89;117;63 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. HIV-1 NL4-3 with an alanine-to-valine substitution at the N-terminus of SP1 (SP1/A1V), which is resistant to bevirimat in vitro, was also resistant to bevirimat treatment in the mice, and SP1/AIV had replication and thymocyte kinetics similar to that of WT NL4-3 with no evidence of fitness impairment in in vivo competition assays. 2007 PloS one Abstract HIV A1V 81 84 SP1;SP1;SP1 72;77;188 75;80;191 18045200 Design, synthesis and biological evaluation of a series of thioamides as non-nucleoside reverse transcriptase inhibitors. While compound (2) exhibited activity against the mutant strain L100I with IC(50) of 70.1 microM, compound (4) showed activity against the mutant strain K103N with IC(50) of 92.7 microM, and compound (8) with activity against the wild type enzyme with IC(50) of 8.9 microM. 2007 Medicinal chemistry (Shariqah (United Arab Emirates)) Abstract HIV K103N;L100I 153;64 158;69 18046962 A comparison of the phenotypic susceptibility profiles of emtricitabine and lamivudine. Both compounds select for the M184V/I mutation resulting in high-level resistance. 2007 Antiviral chemistry & chemotherapy Abstract HIV M184I;M184V 30;30 37;37 18046962 A comparison of the phenotypic susceptibility profiles of emtricitabine and lamivudine. In the absence of M184V/I, the majority of samples with resistance (> 3.5 FC) exhibited TAMs with a trend toward increased levels of cross-resistance with increasing numbers of TAMs. 2007 Antiviral chemistry & chemotherapy Abstract HIV M184I;M184V 18;18 25;25 18046962 A comparison of the phenotypic susceptibility profiles of emtricitabine and lamivudine. Moreover, there was > 90% concordance in resistance calls based on either the biological (1.4-fold) or proposed clinical (3.5-fold) cutoffs among all NRTI-R isolates or isolates with M184V/I mixtures. 2007 Antiviral chemistry & chemotherapy Abstract HIV M184I;M184V 183;183 190;190 NRTI 150 154 18046962 A comparison of the phenotypic susceptibility profiles of emtricitabine and lamivudine. Seventy-two percent had > or = 1 thymidine analogue mutation (TAM), 21% had mixtures at M184, 14% had L74V and 7.5% had K65R. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;L74V 120;102 124;106 18052195 Insights into a mutation-assisted lateral drug escape mechanism from the HIV-1 protease active site. Significant inhibitor deviation is reported over 24 ns, and subsequent complete expulsion, implemented using steered molecular dynamics simulations, is shown to occur most easily for the G48V-containing mutants. 2007 Biochemistry Abstract HIV G48V 187 191 18052195 Insights into a mutation-assisted lateral drug escape mechanism from the HIV-1 protease active site. We find a consistent escape mechanism associated with the G48V mutation. 2007 Biochemistry Abstract HIV G48V 58 62 18052195 Insights into a mutation-assisted lateral drug escape mechanism from the HIV-1 protease active site. We provide insight into the first stages of a kinetic mechanism of lateral drug expulsion from the active site of HIV-1 protease, by conducting all atom molecular dynamics simulations with explicit solvent over a time scale of 24 ns for saquinavir bound to the wildtype, G48V, L90M and G48V/L90M mutant proteases. 2007 Biochemistry Abstract HIV G48V;G48V;L90M;L90M 271;286;291;277 275;290;295;281 PR;PR 120;303 128;312 18052235 Caught in the Act: the 1.5 A resolution crystal structures of the HIV-1 protease and the I54V mutant reveal a tetrahedral reaction intermediate. The mutant PRI54V/TI complex has lost water-mediated hydrogen bond interactions with the amides of Ile50 and Ile50' in the flap. 2007 Biochemistry Abstract HIV I54V 13 19 PR 11 13 18052235 Caught in the Act: the 1.5 A resolution crystal structures of the HIV-1 protease and the I54V mutant reveal a tetrahedral reaction intermediate. We report two high-resolution crystal structures of wild-type PR (PRWT) and the multi-drug-resistant variant with the I54V mutation (PRI54V) in complex with a peptide at 1.46 and 1.50 A resolution, respectively. 2007 Biochemistry Abstract HIV I54V 118 122 PR;PR 62;133 64;135 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Biochemical analyses of recombinant RT containing N348I provide supporting evidence for the role of this mutation in zidovudine and NNRTI resistance and give some insight into the molecular mechanism of resistance. 2007 PLoS medicine Abstract HIV N348I 50 55 NNRTI;RT 132;36 137;38 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. CONCLUSIONS: This study provides the first in vivo evidence that treatment with RT inhibitors can select a mutation (i.e., N348I) outside the polymerase domain of the HIV-1 RT that confers dual-class resistance. 2007 PLoS medicine Abstract HIV N348I 123 128 Pol;RT;RT 142;80;173 152;82;175 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. METHODS AND FINDINGS: The prevalence of N348I in clinical isolates, the time taken for it to emerge under selective drug pressure, and its association with changes in viral load, specific drug treatment, and known drug resistance mutations was analysed from genotypes, viral loads, and treatment histories from the Centre's database. 2007 PLoS medicine Abstract HIV N348I 40 45 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I also decreased susceptibility to nevirapine (7.4-fold) and efavirenz (2.5-fold) and significantly potentiated resistance to these drugs when combined with K103N. 2007 PLoS medicine Abstract HIV K103N;N348I 161;0 166;5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I appeared early in therapy and was highly associated with thymidine analogue mutations (TAMs) M41L and T215Y/F (p < 0.001), the lamivudine resistance mutations M184V/I (p < 0.001), and non-nucleoside RTI (NNRTI) resistance mutations K103N and Y181C/I (p < 0.001). 2007 PLoS medicine Abstract HIV K103N;M184I;M184V;M41L;T215F;T215Y;Y181C;Y181I;N348I 238;165;165;97;108;108;248;248;0 243;172;172;103;115;115;255;255;5 NNRTI;NNRTI 210;190 215;208 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I decreased zidovudine susceptibility 2- to 4-fold in the context of wild-type HIV-1 or when combined with TAMs. 2007 PLoS medicine Abstract HIV N348I 0 5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I increased in prevalence from below 1% in 368 treatment-naive individuals to 12.1% in 1,009 treatment-experienced patients (p = 7.7 x 10(-12)). 2007 PLoS medicine Abstract HIV N348I 0 5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The appearance of N348I was associated with a significant increase in viral load (p < 0.001), which was as large as the viral load increases observed for any of the TAMs. 2007 PLoS medicine Abstract HIV N348I 18 23 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The association with TAMs and NNRTI resistance mutations was consistent with the selection of N348I in patients treated with regimens that included both zidovudine and nevirapine (odds ratio 2.62, 95% confidence interval 1.43-4.81). 2007 PLoS medicine Abstract HIV N348I 94 99 NNRTI 30 35 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The British Columbia Centre for Excellence in HIV/AIDS (the Centre) genotypes clinical isolates up to codon 400 in RT, and our retrospective statistical analyses of the Centre's database have identified an N348I mutation in the RT connection domain in treatment-experienced individuals. 2007 PLoS medicine Abstract HIV N348I 206 211 RT;RT 115;228 117;230 AIDS 50 54 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. To delineate the role of this mutation in RT inhibitor resistance, N348I was introduced into HIV-1 molecular clones containing different genetic backbones. 2007 PLoS medicine Abstract HIV N348I 67 72 RT 42 44 18056282 Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131. Notably, antiviral resistance analysis indicated that neither the K65R, L74V, or M184V RT mutation nor their combinations had any effect on the antiretroviral activity of GS-9148. 2008 Antimicrobial agents and chemotherapy Abstract HIV K65R;L74V;M184V 66;72;81 70;76;86 RT 87 89 18068205 HIV-1 resistance to the anti-HIV activity of a shRNA targeting a dual-coding region. Both mutations are silent in the Env frame, but the mutation 5 generated an amino acid change (V47M) in the Rev reading frame. 2008 Virology Abstract HIV V47M 95 99 Rev;Env 108;33 111;36 18083561 Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). This Letter describes the design, synthesis, and biological evaluation of novel 3-indole sulfonamides as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) with balanced profiles against common HIV RT mutants K103N and Y181C. 2008 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 222;232 227;237 NNRTI;NNRTI;RT 112;161;211 148;167;213 18090283 HIV drug resistance after the use of generic fixed-dose combination stavudine/lamivudine/nevirapine as standard first-line regimen. Early failures to stavudine/lamivudine/nevirapine used as a generic fixed-dose combination in Mali showed resistance mutations in 50% of cases (mostly M184V and Y181C). 2007 AIDS (London, England) Abstract HIV M184V;Y181C 151;161 156;166 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. To characterize the mechanism of AZT resistance we expressed two recombinant reverse transcriptases of highly AZT-resistant SFVmac in Escherichia coli harboring three (K211I, S345T, E350K) or four mutations (K211I, I224T, S345T, E350K) in the reverse transcriptase gene. 2008 Nucleic acids research Abstract HIV E350K;E350K;I224T;K211I;K211I;S345T;S345T 182;229;215;168;208;175;222 187;234;220;173;213;180;227 RT;RT 77;243 99;264 18097236 Prevalence and impact of HIV-1 protease mutation L76V on lopinavir resistance. Besides I47A, mutation L76V at the HIV protease gene has recently been proposed to cause lopinavir resistance. 2008 AIDS (London, England) Abstract HIV I47A;L76V 8;23 12;27 PR 39 47 18097236 Prevalence and impact of HIV-1 protease mutation L76V on lopinavir resistance. Therefore, L76V does not appear to be a primary lopinavir resistance change when the drug is used in combination therapy. 2008 AIDS (London, England) Abstract HIV L76V 11 15 18098141 Molecular epidemiology of HIV-1 subtypes and drug resistant strains in Taiwan. In addition, 126 treatment naive patients were selected for genotypic DR analysis and the results showed that 4.3% (2/47) homosexual males had M184V mutations. 2008 Journal of medical virology Abstract HIV M184V 143 148 18155043 Mechanistic insights into the role of Val75 of HIV-1 reverse transcriptase in misinsertion and mispair extension fidelity of DNA synthesis. Primer extension experiments carried out in the absence of one deoxyribonucleoside-triphosphate suggested that mutations did not affect the accuracy of the RT, except for V75A, V75F, V75I, and to a lesser extent V75T. 2008 Journal of molecular biology Abstract HIV V75A;V75F;V75I;V75T 171;177;183;212 175;181;187;216 RT 156 158 18155043 Mechanistic insights into the role of Val75 of HIV-1 reverse transcriptase in misinsertion and mispair extension fidelity of DNA synthesis. Specific DNA polymerase activities of mutant RTs bearing amino acid substitutions at position 75 (i.e., V75A, V75F, V75I, V75L, V75M, V75S and V75T) were relatively high. 2008 Journal of molecular biology Abstract HIV V75A;V75F;V75I;V75L;V75M;V75S;V75T 104;110;116;122;128;134;143 108;114;120;126;132;138;147 Pol;RT 13;45 23;48 18155043 Mechanistic insights into the role of Val75 of HIV-1 reverse transcriptase in misinsertion and mispair extension fidelity of DNA synthesis. Steady- and pre-steady-state kinetics demonstrated that the increased fidelity of V75I and V75F was related to their decreased ability to extend mismatched template-primers, while misincorporation efficiencies were not significantly affected by mutations. 2008 Journal of molecular biology Abstract HIV V75F;V75I 91;82 95;86 18155043 Mechanistic insights into the role of Val75 of HIV-1 reverse transcriptase in misinsertion and mispair extension fidelity of DNA synthesis. The fidelity of RTs bearing mutations V75F and V75I increased 1.8- and 3-fold, respectively, as measured by the M13 lacZ alpha forward mutation assay, while V75A showed 1.4-fold decreased accuracy. 2008 Journal of molecular biology Abstract HIV V75A;V75F;V75I 157;38;47 161;42;51 RT 16 19 18155043 Mechanistic insights into the role of Val75 of HIV-1 reverse transcriptase in misinsertion and mispair extension fidelity of DNA synthesis. The increased mispair extension fidelity of mutant V75I RT could be attributed to the nucleotide affinity loss, observed in reactions with mismatched template-primers. 2008 Journal of molecular biology Abstract HIV V75I 51 55 RT 56 58 18155520 3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations. Clinically relevant Lys103Asn (K103N) mutant frequently observed in HIV-1 reverse transcriptase (RT) confers drug resistance. 2008 Bioorganic & medicinal chemistry letters Abstract HIV K103N;K103N 20;31 29;36 RT;RT 74;97 95;99 18155520 3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations. The first strategy is the flexibility-based molecular alignment (FMA), similar to receptor-based alignment, which samples the biological space of K103N mutant HIV-RT. 2008 Bioorganic & medicinal chemistry letters Abstract HIV K103N 146 151 RT 163 165 18155520 3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations. The present study introduced the concept 'clamp-flex' for the rational design of targeted-inhibitor to overcome the K103N pan-class resistance mutation. 2008 Bioorganic & medicinal chemistry letters Abstract HIV K103N 116 121 18160002 An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V. Based on this finding, we developed a new MS-PCR assay to detect the M184I/V mutation, and evaluated the assay performance for detecting GPOvir-resistant CRF01_AE cases. 2007 AIDS research and human retroviruses Abstract HIV M184I;M184V 69;69 76;76 18160002 An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V. Comparing the results of M184I/V MS-PCR and sequence analyses, we found a concordance rate of 95% and an overall sensitivity of the M184I/V MS-PCR for detecting GPOvir-resistant cases of 79%. 2007 AIDS research and human retroviruses Abstract HIV M184I;M184I;M184V;M184V 25;132;25;132 32;139;32;139 18160002 An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V. Considering the relatively low price of the assay, approximately $12.50 per sample, M184I/V MS-PCR may be a candidate for monitoring a large number of GPOvir-treated patients, particularly in developing nations. 2007 AIDS research and human retroviruses Abstract HIV M184I;M184V 84;84 91;91 18160002 An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V. The most prevalent drug resistance mutation among the samples was the lamivudine resistance M184I/V mutation. 2007 AIDS research and human retroviruses Abstract HIV M184I;M184V 92;92 99;99 18160009 Persistence of genotypic resistance to nelfinavir among women exposed to prophylactic antiretroviral therapy during pregnancy. NFV resistance was observed in 4 out of 17 (23.5%) patients exposed to this drug: two major mutations D30N (1/17) and L90M (1/17) and minor mutations (N88S, 2/17). 2007 AIDS research and human retroviruses Abstract HIV D30N;L90M;N88S 102;118;151 106;122;155 18160018 Characterization of HIV type 1 reverse transcriptase mutations in infants infected by mothers who received peripartum nevirapine prophylaxis in Jos, Nigeria. Four of 13 (31%) infants had NNRTI resistance mutations--V179I (2 infants), Y181C, and V179E. 2007 AIDS research and human retroviruses Abstract HIV V179E;V179I;Y181C 87;57;76 92;62;81 NNRTI 29 34 18160018 Characterization of HIV type 1 reverse transcriptase mutations in infants infected by mothers who received peripartum nevirapine prophylaxis in Jos, Nigeria. Intriguingly, subtype G sequences did not have NNRTI mutations but rather carried a Q207N mutation, which may undergo negative selection under drug pressure. 2007 AIDS research and human retroviruses Abstract HIV Q207N 84 89 NNRTI 47 52 18160142 Altered sensitivity of an R5X4 HIV-1 strain 89.6 to coreceptor inhibitors by a single amino acid substitution in the V3 region of gp120. An isolated mutant harbored a single amino acid substitution in the V3 region of the Env (arginine 308 to serine R308S). 2008 Antiviral research Abstract HIV R308S;R308S 113;90 118;113 Env 85 88 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. We also replaced wt PR with a slightly less active T26S PR mutant in an effort to prevent premature processing and cytoxicity associated with wt PR. 2007 Retrovirology Abstract HIV T26S 51 55 PR;PR;PR 20;56;145 22;58;147 18164198 Synthesis and anti-HIV activity of GS-9148 (2'-Fd4AP), a novel nucleoside phosphonate HIV reverse transcriptase inhibitor. Unlike many clinical RT inhibitors, relevant reverse transcriptase mutants (M184V, K65R, 6-TAMs) maintain a susceptibility to 2'-Fd4AP that is similar to wild-type virus. 2008 Bioorganic & medicinal chemistry letters Abstract HIV K65R;M184V 83;76 87;81 RT;RT 45;21 66;23 18173253 Conformational analysis of TMC114, a novel HIV-1 protease inhibitor. All 43 conformers were subject to both rigid and flexible ligand docking in the wild-type and a triple mutant (L63P/V82T/I84V) of HIV-1 protease. 2008 Journal of chemical information and modeling Abstract HIV L63P;I84V;V82T 111;121;116 115;125;120 PR 136 144 18178851 CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef. By genetic and functional studies, we found that Arg75Thr and Tyr85Phe mutations, located in a well-conserved proline-rich region in Nef, were differently associated with escape from CTL responses specific for two overlapping HLA-B35-restricted epitopes. 2008 Journal of immunology (Baltimore, Md. Abstract HIV R75T;Y85F 49;62 57;70 Nef 133 136 18178851 CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef. CTLs specific for an epitope, that selected Tyr85Phe, were elicited earlier and had more potent functional avidities than did those that selected Arg75Thr. 2008 Journal of immunology (Baltimore, Md. Abstract HIV R75T;Y85F 146;44 154;52 18180829 [Resistance to anti-retroviral therapy in Chilean patients with HIV-1 from 2002 to 2005]. The most common mutations found were T215Y (46%), L10F (44%), Ml84V (3896), K103N (35%) and M41L (32%). 2007 Revista medica de Chile Abstract HIV K103N;L10F;M41L;T215Y 76;50;92;37 81;54;96;42 18182278 Genotypic resistance profiles in antiretroviral-naive HIV-1 infections before and after initiation of first-line HAART: impact of polymorphism on resistance to therapy. At baseline, the differences between CRF01_AE and B strain were mainly observed in the minor mutations L10I/V, M36I and L63P/I/H (P<0.001, chi(2)). 2008 International journal of antimicrobial agents Abstract HIV L10I;L10V;L63H;L63I;L63P;M36I 103;103;120;120;120;111 109;109;128;128;128;115 18182278 Genotypic resistance profiles in antiretroviral-naive HIV-1 infections before and after initiation of first-line HAART: impact of polymorphism on resistance to therapy. In the reverse transcriptase sequence, M41L and T215Y/S were more common in patients infected with subtype B virus (P<0.05, chi(2)). 2008 International journal of antimicrobial agents Abstract HIV M41L;T215S;T215Y 39;48;48 43;55;55 RT 7 28 18182278 Genotypic resistance profiles in antiretroviral-naive HIV-1 infections before and after initiation of first-line HAART: impact of polymorphism on resistance to therapy. Moreover, major mutations (D30N and N88D) conferring resistance to PIs were found in patients infected with subtype B strain. 2008 International journal of antimicrobial agents Abstract HIV D30N;N88D 27;36 32;40 PI 67 70 18184079 Evolution of genotypic and phenotypic resistance during chronic treatment with the fusion inhibitor T-1249. A novel substitution, A50V (n = 12, 32%), was also common, as were the N126K and S138A substitutions in heptad-repeat 2 (HR-2). 2007 AIDS research and human retroviruses Abstract HIV A50V;N126K;S138A 22;71;81 26;76;86 18184079 Evolution of genotypic and phenotypic resistance during chronic treatment with the fusion inhibitor T-1249. Resistance to T-1249 gradually increased to a geometric mean 92.7-fold decrease from FI-naive baseline; this occurred concomitant with further evolution of gp41 amino acids 36-45, most commonly the G36D (n = 6, 16%) or N43K (n = 9, 24%) substitutions. 2007 AIDS research and human retroviruses Abstract HIV G36D;N43K 198;219 202;223 gp41 156 160 18186529 Resampling-based analyses of the effects of combinations of HIV genetic mutations on drug susceptibility. Analysis of the data from the Stanford HIV database shows that while M46I/L mutations are associated with drug resistance, addition of the L88D/S mutation leads to hypersusceptible virus. 2008 Statistics in medicine Abstract HIV L88D;L88S;M46I;M46L 139;139;69;69 145;145;75;75 18186529 Resampling-based analyses of the effects of combinations of HIV genetic mutations on drug susceptibility. Further addition of T90M/L mutations results in highly resistant virus. 2008 Statistics in medicine Abstract HIV T90L;T90M 20;20 26;26 18195563 Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA. The K103N mutation emerged more in patients failing EFV and Y181C in patients failing NVP. 2008 AIDS (London, England) Abstract HIV K103N;Y181C 4;60 9;65 18195570 Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. A large clinical database was queried to identify antiretroviral-naive patients with V118I as the sole resistance associated mutation. 2008 AIDS (London, England) Abstract HIV V118I 85 90 18195570 Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. Although the V118I mutation in reverse transcriptase causes a reduced incorporation of zidovudine and lamivudine into transcribed viral DNA, it also decreases ATP-mediated pyrophosphorylysis. 2008 AIDS (London, England) Abstract HIV V118I 13 18 RT 31 52 18195570 Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. Furthermore, the presence of V118I as the sole nucleoside reverse transcriptase inhibitor mutation should not be over-interpreted when deciding on therapeutic options. 2008 AIDS (London, England) Abstract HIV V118I 29 34 NRTI 47 79 18195570 Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. Nevertheless, V118I remains identified as a resistance mutation by a number of commonly utilised resistance mutation algorithms. 2008 AIDS (London, England) Abstract HIV V118I 14 19 18195570 Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. Our study suggests that V118I should be excluded from mutation lists used for clinical epidemiological studies of transmitted drug resistance. 2008 AIDS (London, England) Abstract HIV V118I 24 29 18195570 Effect of isolated V118I mutation in reverse transcriptase on response to first-line antiretroviral therapy. The V118I mutation was detected as the sole major reverse transcriptase mutation in 35 (1.8%) samples. 2008 AIDS (London, England) Abstract HIV V118I 4 9 RT 50 71 18212102 Characterization of a novel human immunodeficiency virus type 1 protease inhibitor, A-790742. During in vitro selection, A-790742 selected two primary mutations (V82L and I84V) along with L23I, L33F, K45I, A71V/A, and V77I in the pNL4-3 background and two other mutations (A71V and V82G) accompanied by M46I and L63P in the HIV-1 RF background. 2008 Antimicrobial agents and chemotherapy Abstract HIV A71A;A71V;A71V;I84V;K45I;L23I;L33F;L63P;M46I;V77I;V82G;V82L 112;112;179;77;106;94;100;218;209;124;188;68 118;118;184;81;110;98;104;222;213;128;192;73 18212102 Characterization of a novel human immunodeficiency virus type 1 protease inhibitor, A-790742. HIV-1 pNL4-3 clones with a single V82L or I84V mutation were phenotypically resistant to A-790742 and ritonavir. 2008 Antimicrobial agents and chemotherapy Abstract HIV I84V;V82L 42;34 46;38 18212102 Characterization of a novel human immunodeficiency virus type 1 protease inhibitor, A-790742. The selection of the uncommon V82L and V82G mutations in protease by A-790742 suggests the potential for an advantageous resistance profile with this protease inhibitor. 2008 Antimicrobial agents and chemotherapy Abstract HIV V82G;V82L 39;30 43;34 PR;PR 57;150 65;158 18215016 Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation. In our quest for HIV-1 protease inhibitors that are not affected by the V82A resistance mutation, we have synthesized and tested a second generation set of C2-symmetric HIV-1 protease inhibitors that contain a cyclohexane group at P1 and/or P1'. 2008 Journal of medicinal chemistry Abstract HIV V82A 72 76 PR;PR 23;175 31;183 18215016 Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation. The binding affinity results indicate that these compounds have an improved response to the appearance of the V82A mutation than the parent compound. 2008 Journal of medicinal chemistry Abstract HIV V82A 110 114 18215016 Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation. The X-ray structure of one of these compounds with the V82A HIV-1 PR variant provides the structural rationale for the better resistance profile of these compounds. 2008 Journal of medicinal chemistry Abstract HIV V82A 55 59 PR 66 68 18215978 Association of efavirenz hypersusceptibility with virologic response in ACTG 368, a randomized trial of abacavir (ABC) in combination with efavirenz (EFV) and indinavir (IDV) in HIV-infected subjects with prior nucleoside analog experience. In addition, L74V, when combined with K103N+L100I, may confer a selective advantage to the virus that is independent of its effects on nucleoside resistance. 2008 HIV clinical trials Abstract HIV K103N;L100I;L74V 38;44;13 43;49;17 18215978 Association of efavirenz hypersusceptibility with virologic response in ACTG 368, a randomized trial of abacavir (ABC) in combination with efavirenz (EFV) and indinavir (IDV) in HIV-infected subjects with prior nucleoside analog experience. In some patients on the nucleoside-sparing arm, the nucleoside-resistance mutation L74V was selected for in combination with the uncommonly occurring EFV-resistance mutations K103N+L100I; L74V was not detected as a minority variant, using clonal sequence analysis, when the nucleoside-sparing regimen was initiated. 2008 HIV clinical trials Abstract HIV K103N;L100I;L74V;L74V 175;181;83;188 180;186;87;192 18216099 Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. Acquisition of N348I was frequently observed in AZT- and/or ddI-containing therapy (12.5%; n = 48; P < 0.0001) and was accompanied with thymidine analogue-associated mutations, e.g., T215Y (n = 5/6) and the lamivudine resistance mutation M184V (n = 1/6) in a Japanese cohort. 2008 Journal of virology Abstract HIV M184V;N348I;T215Y 238;15;183 243;20;188 18216099 Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. Molecular modeling analysis shows that residue 348 is proximal to the NNRTI-binding pocket and to a flexible hinge region at the base of the p66 thumb that may be affected by the N348I mutation. 2008 Journal of virology Abstract HIV N348I 179 184 NNRTI 70 75 18216099 Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. N348I impaired HIV-1 replication in a cell-type-dependent manner. 2008 Journal of virology Abstract HIV N348I 0 5 18216099 Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. This resistance is caused by N348I, a mutation at the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). 2008 Journal of virology Abstract HIV N348I 29 34 RT;RT 122;145 143;147 18216099 Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. Virologic analysis showed that N348I conferred multiclass resistance to NNRTIs (NVP and delavirdine) and to nucleoside reverse transcriptase inhibitors (zidovudine [AZT] and didanosine [ddI]). 2008 Journal of virology Abstract HIV N348I 31 36 NRTI;NNRTI 108;72 140;78 18218003 Detection of drug-resistant HIV minorities in clinical specimens and therapy failure. Also in discordant samples from the diagnostic routine, in which rPhenotyping had identified drug resistance, real-time PCR confirmed minute amounts of mutant M184V. 2008 HIV medicine Abstract HIV M184V 159 164 18218003 Detection of drug-resistant HIV minorities in clinical specimens and therapy failure. METHODS: For validation, defined mixes of wild-type and M184V mutant were analysed by rPhenotyping or standard genotyping. 2008 HIV medicine Abstract HIV M184V 56 61 18218003 Detection of drug-resistant HIV minorities in clinical specimens and therapy failure. RESULTS: Allele-specific and real-time PCR methods detected down to 0.3% of mutant M184V. 2008 HIV medicine Abstract HIV M184V 83 88 18218003 Detection of drug-resistant HIV minorities in clinical specimens and therapy failure. The functional assessment was sensitive enough to reveal <1% of mutant M184V in mixed samples. 2008 HIV medicine Abstract HIV M184V 71 76 18218633 Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. Finally, we compared the binary complex structures of wild-type and M184I RTs. 2008 The Journal of biological chemistry Abstract HIV M184I 68 73 RT 74 77 18218633 Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. First, unlike variants with wild-type M184, M184I RT variants displayed significantly reduced DNA polymerase activity at low dNTP concentrations, which is indicative of reduced dNTP binding affinity. 2008 The Journal of biological chemistry Abstract HIV M184I 44 49 Pol;RT 98;50 108;52 18218633 Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. Second, the M184I variant displayed a approximately 10- to 13-fold reduction in dNTP binding affinity, compared with the Met-184 variant. 2008 The Journal of biological chemistry Abstract HIV M184I 12 17 18218633 Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. Third, unlike HIV-1 vectors with wild-type RT, the HIV-1 vector harboring M184I RT failed to transduce cell types containing low dNTP concentrations, such as human macrophage, likely due to the reduced DNA polymerization activity of the M184I RT under low cellular dNTP concentration conditions. 2008 The Journal of biological chemistry Abstract HIV M184I;M184I 74;237 79;242 RT;RT;RT 43;80;243 45;82;245 18218633 Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. This can restrict ground state dNTP binding and lead to inefficient DNA synthesis particularly at low dNTP concentrations, ultimately contributing to viral replication failure in macrophage and instability in vivo of the M184I mutation. 2008 The Journal of biological chemistry Abstract HIV M184I 221 226 18218633 Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. We characterized HIV-1 reverse transcriptase (RT) variants either with or without the (-)-2',3'-deoxy-3'-thiacytidine-resistant M184I mutation isolated from a single HIV-1 infected patient. 2008 The Journal of biological chemistry Abstract HIV M184I 128 133 RT;RT 23;46 44;48 HIV infections 166 180 18218634 Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of Met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect. In this study, we show that the altered properties of the M184I and M184A RT mutants that we have measured, including decreased processivity, a slower rate of primer extension, and increased strand transfer activity, can all be explained by a defect in dNTP utilization. 2008 The Journal of biological chemistry Abstract HIV M184A;M184I 68;58 73;63 RT 74 76 18218634 Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of Met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect. M184A displays an even more severe processivity defect. 2008 The Journal of biological chemistry Abstract HIV M184A 0 5 18218634 Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of Met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect. The 2',3'-dideoxy-3'-thiacytidine drug-resistant M184I HIV-1 reverse transcriptase (RT) has been shown to synthesize DNA with decreased processivity compared with the wild-type RT. 2008 The Journal of biological chemistry Abstract HIV M184I 49 54 RT;RT;RT 61;84;177 82;86;179 18218644 Subtype variability, virological response and drug resistance assessed on dried blood spots collected from HIV patients on antiretroviral therapy in Angola. The most frequent resistance mutations were M184V (70%) and K103N (39%); 65% had mutations conferring resistance to both NA and NNRTI. 2008 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M184V 60;44 65;49 NNRTI 128 133 18218716 Protein structure and oligomerization are important for the formation of export-competent HIV-1 Rev-RRE complexes. The oligomeric assembly of Rev-L18T is impaired but exhibits minor defects in structure and retains a basal level of activity in vivo. 2008 Protein science Abstract HIV L18T 31 35 Rev 27 30 18218716 Protein structure and oligomerization are important for the formation of export-competent HIV-1 Rev-RRE complexes. The prevalence of L18T in infected individuals suggests a positive selection mechanism for L18T modulation of Rev activity that may delay the onset of AIDS. 2008 Protein science Abstract HIV L18T;L18T 18;91 22;95 Rev 110 113 AIDS 151 155 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. CONCLUSION: These results indicate that early L90M mutants can frequently be displaced by viruses carrying independently selected L90M mutations rather than by descendents of the earlier mutants. 2008 Retrovirology Abstract HIV L90M;L90M 46;130 50;134 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. RESULTS: Using L90M allele specific PCR we amplified and sequenced gag-pro regions linked to very early L90M containing HIV variants prior to their emergence and detection as dominant viruses in 15 failed salvage therapy patients. 2008 Retrovirology Abstract HIV L90M;L90M 15;104 19;108 Gag 67 70 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The early minority L90M linked sequences were then compared to those of the later L90M viruses that came to dominate the plasma quasispecies. 2008 Retrovirology Abstract HIV L90M;L90M 19;82 23;86 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. To determine if the common protease inhibitor resistance mutation L90M is only selected once or repeatedly on different HIV genetic backbones during the course of failed anti-viral therapies we analyzed a linked region of the viral genome during the evolution of multi-drug resistance. 2008 Retrovirology Abstract HIV L90M 66 70 PR 27 35 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Using Bayesian evolutionary analysis sampling trees the emergence of L90M containing viruses was seen to take place on multiple occasion in 5 patients, only once for 2 patients and an undetermined number of time for the remaining 8 patients. 2008 Retrovirology Abstract HIV L90M 69 73 18225901 Rapid and accurate prediction of binding free energies for saquinavir-bound HIV-1 proteases. A detailed analysis of the enthalpic/entropic balance of drug-protease interactions explains resistance in L90M in terms of a higher vibrational entropy than in the WT complex, while G48V disrupts critical hydrogen bonds at the inhibitor's binding site and produces an altered, more unfavorable balance of Coulomb and polar desolvation energies. 2008 Journal of the American Chemical Society Abstract HIV G48V;L90M 183;107 187;111 PR 62 70 18225901 Rapid and accurate prediction of binding free energies for saquinavir-bound HIV-1 proteases. Herein we report an application of the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) technique to the ranking of binding affinities of the inhibitor saquinavir with the wild type (WT) and three resistant mutants of HIV-1 protease: L90M, G48V, and G48V/L90M. 2008 Journal of the American Chemical Society Abstract HIV G48V;G48V;L90M;L90M 252;262;267;246 256;266;271;250 PR 236 244 18226532 Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Parallel synthesis, molecular modelling and structure-activity relationship studies on O-[2-(hetero)arylethyl]-N-phenylthiocarbamates. Two TCs were active also at micromolar concentrations against the Y181C- and/or K103N/Y181C-resistant mutants. 2008 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C;Y181C 80;66;86 85;71;91 18226533 Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate. Some TCs were also active at micromolar concentrations against the Y181C and/or K103N/Y181C resistant mutants. 2008 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C;Y181C 80;67;86 85;72;91 18227187 Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. All the mutations identified altered the activities of integrase protein: both 3' processing and strand transfer activities were moderately affected in the E92Q mutant; strand transfer was markedly impaired in the N155H mutant; both activities were strongly impaired in the G140S Q148H mutant; and the E157Q mutant was almost completely inactive. 2008 Antimicrobial agents and chemotherapy Abstract HIV E157Q;E92Q;G140S;N155H;Q148H 302;156;274;214;280 307;160;279;219;285 IN 55 64 18227187 Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. At least four genetic profiles (E92Q, G140S Q148H, N155H, and E157Q) can be associated with in vivo treatment failure and resistance to raltegravir. 2008 Antimicrobial agents and chemotherapy Abstract HIV E157Q;E92Q;G140S;N155H;Q148H 62;32;38;51;44 67;36;43;56;49 18227187 Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Four different mutation profiles were identified in these nine patients: E92Q, G140S Q148H, N155H, and E157Q mutations. 2008 Antimicrobial agents and chemotherapy Abstract HIV E157Q;E92Q;G140S;N155H;Q148H 103;73;79;92;85 108;77;84;97;90 18227187 Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. The E92Q and G140S Q148H profiles were each associated with a 7- to 8-fold decrease in sensitivity, and the N155H mutant was more than 14-fold less sensitive to raltegravir. 2008 Antimicrobial agents and chemotherapy Abstract HIV E92Q;G140S;N155H;Q148H 4;13;108;19 8;18;113;24 18230722 High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations. In the K103N/Y181C RT/TMC278 structure, loss of the aromatic ring interaction caused by the Y181C mutation is counterbalanced by interactions between the cyanovinyl group of TMC278 and the aromatic side chain of Y183, which is facilitated by an approximately 1.5 A shift of the conserved Y(183)MDD motif. 2008 Proc Natl Acad Sci U S A Abstract HIV K103N;Y181C;Y181C 7;13;92 12;18;97 RT 19 21 18230722 High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations. In the L100I/K103N RT/TMC278 structure, the binding mode of TMC278 is significantly altered so that the drug conforms to changes in the binding pocket primarily caused by the L100I mutation. 2008 Proc Natl Acad Sci U S A Abstract HIV K103N;L100I;L100I 13;7;175 18;12;180 RT 19 21 18230722 High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations. The crystal structures of TMC278 in complexes with the double mutant K103N/Y181C (2.1 A) and L100I/K103N HIV-1 RTs (2.9 A) demonstrated that TMC278 adapts to bind mutant RTs. 2008 Proc Natl Acad Sci U S A Abstract HIV K103N;K103N;L100I;Y181C 99;69;93;75 104;74;98;80 RT;RT 111;170 114;173 18240858 Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation. BACKGROUND: The effect of the HIV reverse transcriptase K65R mutation on virological response to salvage therapy has not been clearly defined. 2007 Antiviral therapy Abstract HIV K65R 56 60 RT 34 55 18240858 Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation. CONCLUSIONS: Development of the K65R mutation does not preclude a high rate of virological response to rescue therapy. 2007 Antiviral therapy Abstract HIV K65R 32 36 18240858 Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation. Inclusion of a TA in the salvage regimen and the presence of a M184V mutation could have a favourable effect on virological outcome. 2007 Antiviral therapy Abstract HIV M184V 63 68 18240858 Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation. METHODS: From six Italian clinical centres, all consecutive patients starting salvage antiretroviral therapy after virological failure in the presence of the K65R mutation identified by a genotypic resistance test were selected. 2007 Antiviral therapy Abstract HIV K65R 158 162 18240858 Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation. The presence of M184V and the introduction of lopinavir/ritonavir as new drug were both marginally associated with better outcome. 2007 Antiviral therapy Abstract HIV M184V 16 21 18240863 Predictive factors for response to a boosted dual HIV-protease inhibitor therapy with saquinavir and lopinavir in extensively pre-treated patients. CONCLUSIONS: Baseline HIV-1 RNA < 5.0 log10 and CD4+ T-cell count > 200 cells/microl, lopinavir C(min)GIQ(arch) > 2,000 ng/ml and the absence of viral resistance mutations at V82T/A/F/I/S and 154M/V/L are highly predictive for therapeutic success of a regimen of saquinavir/lopinavir/ ritonavir without RTI in a heterogenic cohort of patients with an extensive pre-treatment history and highly variable pharmacokinetics. 2007 Antiviral therapy Abstract HIV V82A;V82F;V82I;V82S;V82T 175;175;175;175;175 187;187;187;187;187 RT 303 306 18240863 Predictive factors for response to a boosted dual HIV-protease inhibitor therapy with saquinavir and lopinavir in extensively pre-treated patients. Covariates for the decrease of HIV-1 RNA from baseline to week 48 were baseline HIV-1 RNA (P < 0.001), lopinavir C(min)GIQ(arch) (P = 0.013), presence/absence of mutations at V82T/A/F/I/S or 184A/V plus L10I/R/V/F, 154M/V/L or L63P (P = 0.018), and previously taken antiretrovirals (P = 0.034). 2007 Antiviral therapy Abstract HIV L10F;L10I;L10R;L10V;L63P;V82A;V82F;V82I;V82S;V82T 203;203;203;203;227;175;175;175;175;175 213;213;213;213;231;187;187;187;187;187 18240863 Predictive factors for response to a boosted dual HIV-protease inhibitor therapy with saquinavir and lopinavir in extensively pre-treated patients. RESULTS: The analyses detected correlations between the primary outcome parameter and several factors: baseline CD4+ T-cell count (P = 0.001); absence of mutations at V82T/A/F/I/S plus 154M/V/L (P = 0.002) or K20M/R (P = 0.010); and lopinavir C(min)GIQ(arch) (P = 0.046). 2007 Antiviral therapy Abstract HIV K20M;K20R;V82A;V82F;V82I;V82S;V82T 209;209;167;167;167;167;167 215;215;179;179;179;179;179 18240959 Drug resistance-associated genotypic alterations in the pol gene of HIV type 1 isolates in ART-naive individuals in North India. Forty-nine percent had mutations in the hinge (M36I, R41K, H69K) and alpha-helix (L89M) regions of the C-virus protease, which has been linked to increased catalytic activity. 2008 AIDS research and human retroviruses Abstract HIV H69K;L89M;M36I;R41K 59;82;47;53 63;86;51;57 PR 111 119 18240959 Drug resistance-associated genotypic alterations in the pol gene of HIV type 1 isolates in ART-naive individuals in North India. In the protease region it showed a major drug resistance mutation at M46I as well as "minor" positions F53L and T74P. 2008 AIDS research and human retroviruses Abstract HIV F53L;M46I;T74P 103;69;112 107;73;116 PR 7 15 18240959 Drug resistance-associated genotypic alterations in the pol gene of HIV type 1 isolates in ART-naive individuals in North India. In the RT gene, one patient showed a mutation at major NNRTI position G190V. 2008 AIDS research and human retroviruses Abstract HIV G190V 70 75 NNRTI;RT 55;7 60;9 18240962 Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure. In multivariable models adjusting for prior AIDS, baseline CD4 counts, HIV-1 RNA, and calendar year, viral resistance variables associated with increased hazards of clinical progression were the presence of reverse transcriptase substitution T215F (p = 0.002) and the presence of three or more protease substitutions among L33F/I/V, V82A/F/L/T, I84V, and L90M (p = 0.003). 2008 AIDS research and human retroviruses Abstract HIV I84V;L33F;L33I;L33V;L90M;T215F;V82A;V82F;V82L;V82T 345;323;323;323;355;242;333;333;333;333 349;331;331;331;359;247;343;343;343;343 RT;PR 207;294 228;302 AIDS 44 48 18252693 The HIV-1 protease substitution K55R: a protease-inhibitor-associated substitution involved in restoring viral replication. CONCLUSIONS: The K55R mutation is a secondary drug resistance mutation that can improve viral replication capacity in the presence of other primary protease mutations. 2008 The Journal of antimicrobial chemotherapy Abstract HIV K55R 17 21 PR 148 156 18252693 The HIV-1 protease substitution K55R: a protease-inhibitor-associated substitution involved in restoring viral replication. In vitro characterization of the K55R substitution indicated a primary role for this substitution in increasing replicative capacity in the presence of specific protease mutations. 2008 The Journal of antimicrobial chemotherapy Abstract HIV K55R 33 37 PR 161 169 18252693 The HIV-1 protease substitution K55R: a protease-inhibitor-associated substitution involved in restoring viral replication. RESULTS: The K55R mutation, which is not a natural polymorphism, was identified to be strongly associated with protease mutations M46I/L and to a lesser extent L24I, I54V and V82A/T/S/F. 2008 The Journal of antimicrobial chemotherapy Abstract HIV I54V;K55R;L24I;M46I;M46L;V82A;V82F;V82S;V82T 166;13;160;130;130;175;175;175;175 170;17;164;136;136;185;185;185;185 PR 111 119 18257688 Subtype assignment and phylogenetic analysis of HIV type 1 strains in patients from Swaziland. A mutation associated to non nucleoside inhibitors (Y181I) was found in one case showing a prevalence of transmitted drug resistance <5% in Swaziland. 2008 AIDS research and human retroviruses Abstract HIV Y181I 52 57 18267363 Synthesis and biological evaluation of novel 6-substituted 5-alkyl-2-(arylcarbonylmethylthio)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Among them, the 6-(3,5-dimethylbenzyl) analogue 5p was identified as the most promising compound (EC(50)=0.010 microM, SI>31,800) associated with moderate activity against the HIV-1 double mutant RT strain K103N+Y181C. 2008 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 206;212 211;217 RT 196 198 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Both amino acid changes are strongly associated with the well known NRTI-resistance mutations M41L, L210W and T215Y. 2008 Retrovirology Abstract HIV L210W;M41L;T215Y 100;94;110 105;98;115 NRTI 68 72 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. CONCLUSION: In conclusion, we have identified a novel resistance (E40F) and compensatory (K43E) change in HIV-1 RT. 2008 Retrovirology Abstract HIV E40F;K43E 66;90 70;94 RT 112 114 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Introduction of E40F results in an increase in Zidovudine resistance ranging from nine to fourteen fold depending on the RT background and at the same time confers a decrease in viral replication capacity. 2008 Retrovirology Abstract HIV E40F 16 20 RT 121 123 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. RESULTS: A large database (Quest Diagnostics database) was analysed to determine the associations of the E40F and K43E changes with known resistance mutations. 2008 Retrovirology Abstract HIV E40F;K43E 105;114 109;118 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The K43E change does not decrease the susceptibility to Zidovudine but increases viral replication capacity, when combined with E40F, demonstrating a compensatory role for this codon change. 2008 Retrovirology Abstract HIV E40F;K43E 128;4 132;8 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To unravel the role of two of these newly identified changes, E40F and K43E, we investigated their effect on viral drug susceptibility and replicative capacity. 2008 Retrovirology Abstract HIV E40F;K43E 62;71 66;75 18272247 Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase. M41L, T215Y and other thymidine analogue resistance mutations), which in the presence of a pyrophosphate donor (usually ATP) allow the removal of chain-terminating inhibitors from the 3' end of the primer. 2008 Virus research Abstract HIV T215Y;M41L 6;0 11;4 18272247 Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase. Q151M, M184V, etc.), or (ii) increasing the RT's phosphorolytic activity (e.g. 2008 Virus research Abstract HIV M184V;Q151M 7;0 12;5 RT 44 46 18275342 Trend of drug-resistant HIV type 1 emergence among therapy-naive patients in Nagoya, Japan: an 8-year surveillance from 1999 to 2006. In addition, another 17 variants (4.2%, n = 17) with only 215-revertant mutations (T215C/D/G/L/S) that can easily reconvert to the nucleoside analogue-associated mutation of T215Y/F were found. 2008 AIDS research and human retroviruses Abstract HIV T215C;T215D;T215F;T215G;T215L;T215S;T215Y 83;83;174;83;83;83;174 96;96;181;96;96;96;181 18275342 Trend of drug-resistant HIV type 1 emergence among therapy-naive patients in Nagoya, Japan: an 8-year surveillance from 1999 to 2006. The 402 viruses were phylogenetically analyzed, revealing three independent clusters comprising PI-resistant variants with the M46I or L90M mutation, NNRTI-resistant variants with the K103N mutation, and 215-revertant variants. 2008 AIDS research and human retroviruses Abstract HIV K103N;L90M;M46I 184;135;127 189;139;131 NNRTI;PI 150;96 155;98 18275347 Prevalence of genotypic resistance to nucleoside analogues, nonnucleoside analogues, and protease inhibitors in HIV-infected persons in Athens, Greece. L90M (26.5%) was among the most frequently observed single key protease mutations in our series, although variables of V82 and I54 amino acid substitutions were more frequent. 2008 AIDS research and human retroviruses Abstract HIV L90M 0 4 PR 63 71 18275347 Prevalence of genotypic resistance to nucleoside analogues, nonnucleoside analogues, and protease inhibitors in HIV-infected persons in Athens, Greece. M184V (63.6%) and K103N (25.2%) were the most frequent mutations related to NRTIs and NNRTIs, respectively. 2008 AIDS research and human retroviruses Abstract HIV K103N;M184V 18;0 23;5 NNRTI;NRTI 86;76 92;81 18275347 Prevalence of genotypic resistance to nucleoside analogues, nonnucleoside analogues, and protease inhibitors in HIV-infected persons in Athens, Greece. Mutations in the protease gene showed that the ARM at residue L63P was the most prevalent present in 119 samples (50.9%). 2008 AIDS research and human retroviruses Abstract HIV L63P 62 66 PR 17 25 18275347 Prevalence of genotypic resistance to nucleoside analogues, nonnucleoside analogues, and protease inhibitors in HIV-infected persons in Athens, Greece. The most frequent ARMs of each drug category were to NRTIs at codons M184V [present in 149 tests (63.6%)], M41L [79 (33.8%)], K70R [66 (28.2%)], M184VI [58 (24.8%)], T215YF [53 (22.7%)], D67N [82 (35.0%)], T215Y [72 (30.8%)], K219Q [47 (20.1%)], K219E/Q [54 (23.1%)], and L210W [49 (20.9%)], respectively. 2008 AIDS research and human retroviruses Abstract HIV D67N;K219E;K219Q;K219Q;K70R;L210W;M184I;M184V;M184V;M41L;T215F;T215Y;T215Y 187;246;226;246;126;272;145;69;145;107;166;166;206 191;253;231;253;130;277;151;74;151;111;172;172;211 NRTI 53 58 18275347 Prevalence of genotypic resistance to nucleoside analogues, nonnucleoside analogues, and protease inhibitors in HIV-infected persons in Athens, Greece. The most prevalent mutations related to NNRTIs were K103N [present in 59 tests (25.2%)], G190A [50 (21.4%)], and Y181C [48 (20.5%]. 2008 AIDS research and human retroviruses Abstract HIV G190A;K103N;Y181C 89;52;113 94;57;118 NNRTI 40 46 18275351 Prevalence of primary antiretroviral resistance: trends in Korea. Two (2.5%) were infected with primary drug-resistant virus: M41L and K103N, respectively. 2008 AIDS research and human retroviruses Abstract HIV K103N;M41L 69;60 74;64 18277921 Vertical transmission of multidrug-resistant Q151M human immunodeficiency virus type 1 strains. We report the first case of mother-to-child transmission of human immunodeficiency virus type 1 strains harboring multiple mutations including the Q151M multinucleoside reverse transcriptase inhibitor resistance mutation. 2008 The Pediatric infectious disease journal Abstract HIV Q151M 147 152 RT 169 190 18281688 Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. Although complexation with RPB stabilizes both dimers, the effect on their T(m) is smaller for PR(D25N) (6.2 degrees C) than for PR (8.7 degrees C). 2008 The Journal of biological chemistry Abstract HIV D25N 98 102 PR;PR 95;129 97;131 18281688 Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. In the absence of inhibitor, NMR studies reveal clear structural differences between PR and PR(D25N) in the relatively mobile P1 loop (residues 79-83) and flap regions, and differential scanning calorimetric analyses show that the mutation lowers the stabilities of both the monomer and dimer folds by 5 and 7.3 degrees C, respectively. 2008 The Journal of biological chemistry Abstract HIV D25N 95 99 PR;PR 85;92 87;94 18281688 Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. Only minimal differences are observed in high resolution crystal structures of PR(D25N) complexed to darunavir (DRV), a potent clinical inhibitor, or a non-hydrolyzable substrate analogue, Ac-Thr-Ile-Nle-r-Nle-Gln-Arg-NH(2) (RPB), as compared with PR.DRV and PR.RPB complexes. 2008 The Journal of biological chemistry Abstract HIV D25N 82 86 PR;PR;PR 79;248;259 81;250;261 18281688 Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. The D25N mutation (PR(D25N)) increases the equilibrium dimer dissociation constant by a factor >100-fold (1.3 +/- 0.09 microm) relative to PR. 2008 The Journal of biological chemistry Abstract HIV D25N;D25N 4;22 8;26 PR;PR 19;139 21;141 18281688 Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. The T(m) of PR(D25N).DRV increases by only 3 degrees C relative to free PR(D25N), as compared with a 22 degrees C increase for PR.DRV, and the mutation increases the ligand dissociation constant of PR(D25N).DRV by a factor of approximately 10(6) relative to PR.DRV. 2008 The Journal of biological chemistry Abstract HIV D25N;D25N;D25N 15;75;201 19;79;205 PR;PR;PR;PR;PR 12;72;127;198;258 14;74;129;200;260 18281688 Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. We have systematically assessed the effect of the D25N mutation on the structure and stability of the mature PR monomer and dimer. 2008 The Journal of biological chemistry Abstract HIV D25N 50 54 PR 109 111 18284323 A radiolabeled oligonucleotide ligation assay demonstrates the high frequency of nevirapine resistance mutations in HIV type 1 quasispecies of NVP-treated and untreated mother-infant pairs from Uganda. By OLA, 43% of the NVP-treated group had K103N and/or Y181C mutations in their HIV-1 population, using >0.6% cutoff based on a comparative clonal analysis of clinical isolates. 2008 AIDS research and human retroviruses Abstract HIV K103N;Y181C 41;54 46;59 18284323 A radiolabeled oligonucleotide ligation assay demonstrates the high frequency of nevirapine resistance mutations in HIV type 1 quasispecies of NVP-treated and untreated mother-infant pairs from Uganda. Only 16% of the NVP-treated infected mothers and infants harbored either the K103N or the Y181C at 6 weeks postdelivery. 2008 AIDS research and human retroviruses Abstract HIV K103N;Y181C 77;90 82;95 18284323 A radiolabeled oligonucleotide ligation assay demonstrates the high frequency of nevirapine resistance mutations in HIV type 1 quasispecies of NVP-treated and untreated mother-infant pairs from Uganda. Surprisingly, an equal fraction of the untreated and NVP-treated mother-infant group had the K103N mutation in their HIV-1 population in the range of 0.6-5%. 2008 AIDS research and human retroviruses Abstract HIV K103N 93 98 18284323 A radiolabeled oligonucleotide ligation assay demonstrates the high frequency of nevirapine resistance mutations in HIV type 1 quasispecies of NVP-treated and untreated mother-infant pairs from Uganda. The majority of these samples (n = 107) were then analyzed using a radiolabeled oligonucleotide ligation assay (OLA) specific for K70R, K103N, and Y181C, using nonstandard bases to accommodate sequence heterogeneity. 2008 AIDS research and human retroviruses Abstract HIV K103N;K70R;Y181C 136;130;147 141;134;152 18284323 A radiolabeled oligonucleotide ligation assay demonstrates the high frequency of nevirapine resistance mutations in HIV type 1 quasispecies of NVP-treated and untreated mother-infant pairs from Uganda. The prevalence of the K103N mutations may be related to its low fitness cost and high genetic stability. 2008 AIDS research and human retroviruses Abstract HIV K103N 22 27 18284323 A radiolabeled oligonucleotide ligation assay demonstrates the high frequency of nevirapine resistance mutations in HIV type 1 quasispecies of NVP-treated and untreated mother-infant pairs from Uganda. These findings suggest a relatively high frequency of K103N mutation in the drug-naive, subtype A and D infected Ugandan population as compared to the very low frequency of the Y181C and K70R mutation (<0.6%). 2008 AIDS research and human retroviruses Abstract HIV K103N;K70R;Y181C 54;187;177 59;191;182 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). Deletion of C12L, A44L, A46R or B7R did not significantly affect CD8(+) T cell immunogenicity in BALB/c mice, but deletion of B15R enhanced specific CD8(+) T cell responses to one of two endogenous viral epitopes (from the E2 and F2 proteins), in accordance with published work (Staib et al., 2005, J. 2008 PloS one Abstract HIV A44L;A46R;C12L 18;24;12 22;28;16 18288973 Human immunodeficiency virus-induced apoptosis of human breast cancer cells via CXCR4 is mediated by the viral envelope protein but does not require CD4. Furthermore, the gp120 mutant (E370R) with a low CD4 binding ability can specifically induce apoptosis in breast cancer cells but not in T-cells. 2008 Current HIV research Abstract HIV E370R 31 36 gp120 17 22 Breast cancer 106 119 18295909 Improvement in allele-specific PCR assay with the use of polymorphism-specific primers for the analysis of minor variant drug resistance in HIV-1 subtype C. Specifically, the use of a "universal" set of ASPCR primers caused an overestimation of the K103N (ntAAC) mutation at position 103 of reverse transcriptase when primer binding site polymorphisms resided close to the 3' end of the allele-specific primer. 2008 Journal of virological methods Abstract HIV K103N 92 97 RT 134 155 18304321 Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: analysis of the HIV-2 Belgium and Luxembourg database. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naive patients. 2008 BMC infectious diseases Abstract HIV K65R;M184V 31;40 35;45 18304321 Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: analysis of the HIV-2 Belgium and Luxembourg database. The most frequent mutations selected under therapy (compared to HIV-2 ROD) were V71I, L90M and I89V within PR. 2008 BMC infectious diseases Abstract HIV I89V;L90M;V71I 95;86;80 99;90;84 PR 107 109 18304321 Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: analysis of the HIV-2 Belgium and Luxembourg database. Within RT, they were M184V, Q151M, V111I and K65R. 2008 BMC infectious diseases Abstract HIV K65R;M184V;Q151M;V111I 45;21;28;35 49;26;33;40 RT 7 9 18311928 Crystal structures of highly constrained substrate and hydrolysis products bound to HIV-1 protease. Implications for the catalytic mechanism. The structure of the inactive HIVPR(D25N)/substrate complex shows an intact substrate molecule in a single orientation that perfectly mimics the binding of conventional peptide ligands of HIVPR. 2008 Biochemistry Abstract HIV D25N 36 40 18311928 Crystal structures of highly constrained substrate and hydrolysis products bound to HIV-1 protease. Implications for the catalytic mechanism. The substrate has been cocrystallized with catalytically active synthetic HIV-1 protease and an inactive isosteric (D25N) mutant, and three-dimensional structures were determined (1.60 A). 2008 Biochemistry Abstract HIV D25N 116 120 PR 80 88 18313784 Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase. The resistance mechanism can be NNRTI-dependent as is the case for K101E where either indirect (nevirapine) or direct effects (efavirenz) apply. 2008 Virus research Abstract HIV K101E 67 72 NNRTI 32 37 18313784 Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase. V108I (via perturbation of Tyr188 and Tyr181) and K103N (apo-enzyme stabilisation). 2008 Virus research Abstract HIV K103N;V108I 50;0 55;5 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. By logistic regression analysis only plasma HIV-1 RNA at failure correlated with the occurrence of K65R mutations [OR 4.2 (95% CI, 1.5-11.2) per 0.5log copies/mL increment of HIV-1 RNA]. 2008 Journal of clinical virology Abstract HIV K65R 99 103 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. CONCLUSIONS: Seven percent of patients had K65R mutations after failing an initial d4T/3TC/NVP regimen. 2008 Journal of clinical virology Abstract HIV K65R 43 47 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. HIV-1 RNA at the time that virological failure was detected correlated with the occurrence of K65R mutations. 2008 Journal of clinical virology Abstract HIV K65R 94 98 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. K65R mutations that occur after failing this regimen prevent the use of tenofovir, didanosine, and abcavir in the second-line regimen. 2008 Journal of clinical virology Abstract HIV K65R 0 4 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. OBJECTIVES: To determine the prevalence and risk factors of K65R mutations after failing d4T/3TC/NVP. 2008 Journal of clinical virology Abstract HIV K65R 60 64 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. Patients with K65R mutations had higher plasma HIV-1 RNA at virological failure compared to patients without K65R mutations (4.9log copies/mL vs. 2008 Journal of clinical virology Abstract HIV K65R;K65R 14;109 18;113 18316243 Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine. The prevalence of K65R mutations was 7%. 2008 Journal of clinical virology Abstract HIV K65R 18 22 18316521 Entecavir exhibits inhibitory activity against human immunodeficiency virus under conditions of reduced viral challenge. Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. 2008 Antimicrobial agents and chemotherapy Abstract HIV M184I 25 30 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. For most NRTIs, the primary mechanism of resistance by K65R, M184V and K65R+M184V mutant RTs is to disrupt the NRTI-binding/incorporation steps. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;K65R;M184V;M184V 55;71;61;76 59;75;66;81 NRTI;NRTI;RT 9;111;89 14;115;92 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. For TFV, decreased excision by K65R and K65R+M184V may partially counteract the K65R-driven decrease in incorporation relative to wild-type resulting in only low levels of TFV resistance. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;K65R;K65R;M184V 31;40;80;45 35;44;84;50 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. In cell culture, the K65R+M184V virus showed slightly increased susceptibility to TFV, AZT and d4T compared with K65R alone, but showed further decreases in susceptibility to 3TC, FTC, ddl and abacavir. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;K65R;M184V 21;113;26 25;117;31 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. In the case of AZT, however, decreased binding/incorporation by K65R and K65R+M184V was counteracted by decreased AZT excision resulting in wild-type susceptibility. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;K65R;M184V 64;73;78 68;77;83 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. M184V mutants have reduced susceptibility to lamivudine (3TC), emtricitabine (FTC) and didanosine (ddl), and contribute to reduced susceptibility to abacavir; however, they remain fully susceptible to tenofovir (TFV), AZT and stavudine (d4T). 2007 Antiviral chemistry & chemotherapy Abstract HIV M184V 0 5 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. The HIV-1 reverse transcriptase (RT) resistance mutations K65R and M184V occur individually and in combination, and can contribute to decreased treatment responses in patients. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;M184V 58;67 62;72 RT;RT 10;33 31;35 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. The K65R-mediated effect on decreasing NRTI excision was stronger than for M184V. 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R;M184V 4;75 8;80 NRTI 39 43 18320935 The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V. Virus carrying K65R have reduced susceptibility to most NRTIs, but retain full susceptibility to zidovudine (AZT). 2007 Antiviral chemistry & chemotherapy Abstract HIV K65R 15 19 NRTI 56 61 18321979 Mutations in the human immunodeficiency virus type 1 polypurine tract (PPT) reduce the rate of PPT cleavage and plus-strand DNA synthesis. We used HIV-1 vectors containing two PPTs and the D116N integrase active-site mutation in a cell-based assay to measure differences in the relative rates of PPT processing and utilization. 2008 Journal of virology Abstract HIV D116N 50 55 IN 56 65 18325896 The involvement of HIV-1 RNAse H in resistance to nucleoside analogues. In vitro, the mutations H539N and D549N decreased the frequency of RT template-switching and, thereby, increased the time for excision of incorporated NRTIs, and thus enhanced NRTI resistance. 2008 The Journal of antimicrobial chemotherapy Abstract HIV D549N;H539N 34;24 39;29 NRTI;NRTI;RT 151;176;67 156;180;69 18327981 Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient. Overall, our findings suggest that the Y181C resistance mutation may be selected, not only by NNRTIs, but also by d4T. 2008 AIDS research and human retroviruses Abstract HIV Y181C 39 44 NNRTI 94 100 18327981 Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient. Phylogenetic analysis including sequences from the index patient and his spouse sampled at different time points, as well as control sequences belonging to the same HIV-1 subtype, revealed that there is no evidence of coinfection or reinfection with Y181C resistance strains, while the virus for both subjects was classified as subtype CRF14_BG. 2008 AIDS research and human retroviruses Abstract HIV Y181C 250 255 18327981 Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient. The particular mutation (Y181C) was not present at any time point during the treatment period with 3TC + AZT + IDV. 2008 AIDS research and human retroviruses Abstract HIV Y181C 25 30 18327981 Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient. The purpose of our study was to examine the emergence of the Y181C resistance mutation in an NNRTI-naive subject (index patient) at different time points. 2008 AIDS research and human retroviruses Abstract HIV Y181C 61 66 NNRTI 93 98 18327981 Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient. The Y181C mutation was detected for the first time when the patient was receiving d4T + ddI + LPV/r; the previous drug combination was 3TC + AZT + IDV. 2008 AIDS research and human retroviruses Abstract HIV Y181C 4 9 18327988 HIV type 1 pol gene diversity and antiretroviral drug resistance mutations in Santos, Brazil. Drug resistance mutations identified in common to subtypes B, F, and recombinants B/F were protease inhibitors M46I/L (29%), I54V (24%), A71V (22%), and V82A/F (31%); reverse transcriptase nucleoside resistance mutations M41L (52%), D67N (30%), K70R (26%), M184V (88%), L210W (29%), T215Y/I/F (65%), and K219Q/E/N (28%); and reverse transcriptase nonnucleoside resistance mutation K103N (52%). 2008 AIDS research and human retroviruses Abstract HIV A71V;D67N;I54V;K103N;K219E;K219N;K219Q;K70R;L210W;M184V;M41L;M46I;M46L;T215F;T215I;T215Y;V82A;V82F 137;233;125;381;304;304;304;245;270;257;221;111;111;283;283;283;153;153 141;237;129;386;313;313;313;249;275;262;225;117;117;292;292;292;159;159 RT;RT;PR 167;325;91 188;346;99 18332076 Long-term safety and efficacy results of once-daily emtricitabine-based highly active antiretroviral therapy regimens in human immunodeficiency virus-infected pediatric subjects. Genotypic analysis showed the emergence of the M184V mutation in 4 of the 15 subjects who experienced virologic failure through week 164. 2008 Pediatrics Abstract HIV M184V 47 52 18336260 Impact of residues in the nonnucleoside reverse transcriptase inhibitor binding pocket on HIV-1 reverse transcriptase heterodimer stability. Notably, the G190W mutation increased RT dimer stability almost to the same extent as did 5 microM efavirenz. 2008 Current HIV research Abstract HIV G190W 13 18 RT 38 40 18336260 Impact of residues in the nonnucleoside reverse transcriptase inhibitor binding pocket on HIV-1 reverse transcriptase heterodimer stability. We found that the mutations K101A, P225H, Y318F and Y318W decreased RT heterodimer stability whereas K103N, V108I, V108W, Y181C, Y188L, G190A, G190E, G190W and P225W increased RT heterodimer stability. 2008 Current HIV research Abstract HIV G190A;G190E;G190W;K101A;K103N;P225H;P225W;V108I;V108W;Y181C;Y188L;Y318F;Y318W 136;143;150;28;101;35;160;108;115;122;129;42;52 141;148;155;33;106;40;165;113;120;127;134;47;57 RT;RT 68;176 70;178 18338369 A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1 reverse transcriptase based on the ONIOM method. A three-layered ONIOM model was used to study the interactions between efavirenz and the binding sites of HIV-1 reverse transcriptase (RT): wild-type and double mutant K103N/Y181C enzyme forms. 2008 ChemMedChem Abstract HIV K103N;Y181C 168;174 173;179 RT;RT 112;135 133;137 18338369 A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1 reverse transcriptase based on the ONIOM method. The calculated binding energy for the efavirenz-K103N/Y181C HIV-1 RT complex is less than that with the wild-type complex by approximately 8 kcal mol(-1). 2008 ChemMedChem Abstract HIV K103N;Y181C 48;54 53;59 RT 66 68 18338369 A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1 reverse transcriptase based on the ONIOM method. The interaction energies, calculated at the MP2/6-31G(d,p) level between efavirenz and individual residues surrounding the binding pocket of the K103N/Y181C enzyme, demonstrate that the attractive interactions between efavirenz and residue positions 101 and 103 were less than those for wild-type RT by 5.52 and 3.62 kcal mol(-1), respectively. 2008 ChemMedChem Abstract HIV K103N;Y181C 145;151 150;156 RT 297 299 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. Absence of selection of K70E in 850 HIV-1-infected naive patients suggests its role in NRTI drug resistance. 2008 Journal of medical virology Abstract HIV K70E 24 28 NRTI 87 91 HIV infections 36 50 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. According to occurrence of K70E mutation after failure to TDF regimen, this mutation was recently reported as a mutation associated with TDF resistance in most resistance genotypic algorithms. 2008 Journal of medical virology Abstract HIV K70E 27 31 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. At the time of K70E selection, 60% of patients had received or received TDF-containing regimen and one-third received exclusive NRTI regimen. 2008 Journal of medical virology Abstract HIV K70E 15 19 NRTI 128 132 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. Concomitant association of K65R and K70E was possible but infrequent (11%). 2008 Journal of medical virology Abstract HIV K65R;K70E 27;36 31;40 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. Conversely with K65R mutation, thymidine analog mutations (TAMs) can be concomitantly observed with K70E mutation but its frequency decreased as the number of TAM increases. 2008 Journal of medical virology Abstract HIV K65R;K70E 16;100 20;104 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. In conclusion, the K70E mutation could be an alternative pathway of TDF resistance, but as the K65R mutation, other NRTI as ABC, ddI, and 3TC could be also associated with the K70E selection. 2008 Journal of medical virology Abstract HIV K65R;K70E;K70E 95;19;176 99;23;180 NRTI 116 120 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. Key mutation associated with resistance to TDF is a K65R in the reverse transcriptase (RT) gene. 2008 Journal of medical virology Abstract HIV K65R 52 56 RT;RT 64;87 85;89 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. Prevalence of K70E RT was low (99/41601, 0.24%) in patients treated between 1999 and 2005. 2008 Journal of medical virology Abstract HIV K70E 14 18 RT 19 21 18360911 National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation. The aim of this study was to analyze, retrospectively, the prevalence and conditions of selection of HIV-1 RT K70E mutation from a national clinical survey. 2008 Journal of medical virology Abstract HIV K70E 110 114 RT 107 109 18366188 Probing the active site steric flexibility of HIV-1 reverse transcriptase: different constraints for DNA- versus RNA-templated synthesis. We also report kinetics data for two HIV-1 RT mutants reported to have altered fidelity (F61A and K65R) using DNA templates containing nonpolar base analogues, and find that one of these (F61A) is a high-fidelity enzyme that appears to be sensitive to a loss of hydrogen-bonding groups. 2008 Biochemistry Abstract HIV F61A;F61A;K65R 89;188;98 94;192;102 RT 43 45 18366310 Short communication: the number of HIV major NRTI mutations correlates directly with other antiretroviral-associated mutations and indirectly with replicative capacity and reduced drug susceptibility. RC declined from a mean of 97.8% for samples without NRTI-DRMs to 68.9% with one NRTI-DRM, possibly due to reduced fitness conferred by K65R or M184I/V, to an RC of 43.9% for samples with seven to eight NRTI-DRMs. 2008 AIDS research and human retroviruses Abstract HIV K65R;M184I;M184V 136;144;144 140;151;151 NRTI;NRTI;NRTI 53;81;203 57;85;207 18366313 Prevalence of resistance mutations in HIV-1-Infected Hondurans at the beginning of the National Antiretroviral Therapy Program. K103N mutations were present in 3.0% of study specimens. 2008 AIDS research and human retroviruses Abstract HIV K103N 0 5 18366313 Prevalence of resistance mutations in HIV-1-Infected Hondurans at the beginning of the National Antiretroviral Therapy Program. The prevalence of nucleoside reverse transcriptase inhibitor mutations was 7.7% with M184V and T215F/Y present in 6.0% and 3.0%, respectively. 2008 AIDS research and human retroviruses Abstract HIV M184V;T215F;T215Y 85;95;95 90;102;102 NRTI 18 50 18368496 Possible allosteric interactions of monoindazole-substituted P2 cyclic urea analogues with wild-type and mutant HIV-1 protease. Similar QSAR models were also observed for the biological activity of these molecules tested against a panel of mutant viruses including mutant strains with single amino acid substitution (I84V), double amino acid substitutions (I84V/V82F), and multiple amino acid changes corresponding to mutations observed in clinical isolates of patients treated with Ritonavir((R)). 2008 Journal of computer-aided molecular design Abstract HIV I84V;I84V;V82F 229;189;234 233;193;238 18370589 Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. A cutoff of 0.5% K103N for detection of K103N was used for both assays. 2008 AIDS research and human retroviruses Abstract HIV K103N;K103N 17;40 22;45 18370589 Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. Forty-six samples (73.0%) were positive for K103N by both assays and 13 samples (20.6%) were negative by both assays. 2008 AIDS research and human retroviruses Abstract HIV K103N 44 49 18370589 Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. Results for the percentage K103N were similar for the two assays (R(2) = 0.92). 2008 AIDS research and human retroviruses Abstract HIV K103N 27 32 18370589 Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. The percentage K103N determined by clonal analysis was consistent with the LigAmp result for five of eight samples, and was consistent with the ASPCR result for three of eight samples. 2008 AIDS research and human retroviruses Abstract HIV K103N 15 20 18370589 Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. The percentage K103N was also determined by analyzing 40 HIV clones from each of these eight samples, using a combined amplification/sequencing method (AmpliSeq). 2008 AIDS research and human retroviruses Abstract HIV K103N 15 20 18370589 Comparison of LigAmp and an ASPCR assay for detection and quantification of K103N-containing HIV variants. We compared the ability of the LigAmp assay and an ASPCR assay to detect and quantify K103N-containing HIV variants in samples from 63 women who received single-dose nevirapine in a clinical trial. 2008 AIDS research and human retroviruses Abstract HIV K103N 86 91 18378713 Mutations in human immunodeficiency virus type 1 integrase confer resistance to the naphthyridine L-870,810 and cross-resistance to the clinical trial drug GS-9137. In conclusion, the accumulation of L74M, E92Q, and S230N mutations in the integrase causes resistance to the naphthyridine L-870,810 and cross-resistance to GS-9137. 2008 Antimicrobial agents and chemotherapy Abstract HIV E92Q;L74M;S230N 41;35;51 45;39;56 IN 74 83 18378713 Mutations in human immunodeficiency virus type 1 integrase confer resistance to the naphthyridine L-870,810 and cross-resistance to the clinical trial drug GS-9137. The L74M and E92Q mutations have both been associated in the past with resistance against the diketo acid (DKA) analogues L-708,906 and S-1360 and the clinical trial drugs MK-0518 and GS-9137. 2008 Antimicrobial agents and chemotherapy Abstract HIV E92Q;L74M 13;4 17;8 18378713 Mutations in human immunodeficiency virus type 1 integrase confer resistance to the naphthyridine L-870,810 and cross-resistance to the clinical trial drug GS-9137. The mutations L74M, E92Q, and S230N were successively selected in the integrase. 2008 Antimicrobial agents and chemotherapy Abstract HIV E92Q;L74M;S230N 20;14;30 24;18;35 IN 70 79 18385244 Human immunodeficiency virus type 1 Vpr binds to the N lobe of the Wee1 kinase domain and enhances kinase activity for CDC2. However, the Vpr mutants I74P and I81P, which fail to induce G(2) arrest, can bind to and increase the kinase activity of Wee1 to the same extent as wild-type Vpr. 2008 Journal of virology Abstract HIV I74P;I81P 25;34 29;38 Vpr;Vpr 13;159 16;162 18385767 Tissue-specific restriction of cyclophilin A-independent HIV-1- and SIV-derived lentiviral vectors. Here, the effect of lentiviral CypA dependence on restriction in different tissues was examined by engineering an HIV-1 capsid quadruple mutant (V(86)P/H(87)Q/I(91)V/M(96)I) lentiviral vector (HIV(quad)) that is CypA-independent. 2008 Gene therapy Abstract HIV V86P;H87Q;I91V;V86P 144;152;160;145 151;158;165;151 Capsid 120 126 18389906 Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues. By contrast, the tenofovir resistance mutation K65R induces a broad 'k(pol)-dependent' nonspecific discrimination towards the three ANPs. 2008 Antiviral therapy Abstract HIV K65R 47 51 Pol 71 74 18389906 Gln151 of HIV-1 reverse transcriptase acts as a steric gate towards clinically relevant acyclic phosphonate nucleotide analogues. Interactions between the Gln151 residue and the methyl group of tenofovir-DP further increase with the mutation Gln151Met, resulting in a specific discrimination and low-level resistance to tenofovir-DP. 2008 Antiviral therapy Abstract HIV Q151M 112 121 18389908 Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen. Analysis of K103N by SPCR showed that 35% of the patients contained < or =0.1% of viruses carrying either the AAC or AAT mutations. 2008 Antiviral therapy Abstract HIV K103N 12 17 18389908 Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen. For M184V mutation, one patient contained 6.2% of virus with GTG mutation and 13 patients (65%) contained <0.9% of mutated viruses. 2008 Antiviral therapy Abstract HIV M184V 4 9 18389908 Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen. For Y181C mutation, 10% of the patients contained <0.5% of viruses with TGT codon change. 2008 Antiviral therapy Abstract HIV Y181C 4 9 18389908 Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen. Sequence-selective real-time PCR (SPCR), which quantifies minority viral populations containing K103N, Y181C and M184V mutations, and standard genotypic sequencing were assayed. 2008 Antiviral therapy Abstract HIV K103N;M184V;Y181C 96;113;103 101;118;108 18390885 Clinically validated mutation scores for HIV-1 resistance to fosamprenavir/ritonavir. Both scores were independent predictors of VR, however, co-administration of tenofovir was associated with a worse VR and the presence of the N88S protease mutation and co-administration of enfuvirtide with a better VR. 2008 The Journal of antimicrobial chemotherapy Abstract HIV N88S 142 146 PR 147 155 18390885 Clinically validated mutation scores for HIV-1 resistance to fosamprenavir/ritonavir. The fosamprenavir/ritonavir score A was introduced in the 2006 ANRS algorithm along with isolated mutations I50V and V32I + I47V. 2008 The Journal of antimicrobial chemotherapy Abstract HIV I47V;I50V;V32I 124;108;117 128;112;121 18390885 Clinically validated mutation scores for HIV-1 resistance to fosamprenavir/ritonavir. Two fosamprenavir/ritonavir mutation scores were constructed: score A (L10F/I/V + L33F + M36I + I54L/M/V/A/T/S + I62V + V82A/F/C/G + I84V + L90M) was based only on mutations associated with a worse VR, whereas score B (L10FIV + L33F + M36I + I54L/M/V/A/T/S + A71V - V77I - N88S + L90M) also took into account favourable mutations. 2008 The Journal of antimicrobial chemotherapy Abstract HIV A71V;I54A;I54A;I54L;I54L;I54M;I54M;I54S;I54S;I54T;I54T;I54V;I54V;I62V;I84V;L10F;L10F;L10I;L10I;L10V;L10V;L33F;L33F;L90M;L90M;M36I;M36I;N88S;V77I;V82A;V82C;V82F;V82G 259;96;242;96;242;96;242;96;242;96;242;96;242;113;133;219;71;219;71;219;71;82;228;140;280;89;235;273;266;120;120;120;120 263;110;256;110;256;110;256;110;256;110;256;110;256;117;137;226;80;226;80;226;80;86;232;144;284;93;239;277;270;130;130;130;130 18391035 Mechanism of inhibition of human immunodeficiency virus type 1 reverse transcriptase by a stavudine analogue, 4'-ethynyl stavudine triphosphate. In general, the M184V mutant exhibits poorer binding for all three nucleoside triphosphates than does wt RT. 2008 Antimicrobial agents and chemotherapy Abstract HIV M184V 16 21 RT 105 107 18391035 Mechanism of inhibition of human immunodeficiency virus type 1 reverse transcriptase by a stavudine analogue, 4'-ethynyl stavudine triphosphate. Using steady-state kinetic approaches, we have previously shown that (i) 4'-ethynyl-d4T triphosphate (4'-Ed4TTP) inhibits HIV-1 RT more efficiently than d4TTP does and (ii) its inhibition efficiency toward the RT M184V mutant is threefold less than that toward wild-type (wt) RT. 2008 Antimicrobial agents and chemotherapy Abstract HIV M184V 213 218 RT;RT;RT 128;210;276 130;212;278 18391035 Mechanism of inhibition of human immunodeficiency virus type 1 reverse transcriptase by a stavudine analogue, 4'-ethynyl stavudine triphosphate. With wt and the M184V mutant RTs, 4'-Ed4TTP has three- to fivefold-lower K(d) (dissociation constant) values than d4TTP, while d4TTP has up to eightfold-higher K(d) values than dTTP. 2008 Antimicrobial agents and chemotherapy Abstract HIV M184V 16 21 RT 29 32 18394758 Synthesis and anti-HIV-1 integrase activities of 3-aroyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazines. Compound 17 as well its analogues were 5-20-fold less potent in Y99S and H114A mutants, implicating these residues as potential drug-binding site. 2009 European journal of medicinal chemistry Abstract HIV H114A;Y99S 73;64 78;68 18394758 Synthesis and anti-HIV-1 integrase activities of 3-aroyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazines. This is a first report implicating Y99S and H114A of IN core domain in drug-binding interactions. 2009 European journal of medicinal chemistry Abstract HIV H114A;Y99S 44;35 49;39 IN 53 55 18396668 [Study on genotypic resistance mutations to antiretroviral drugs on HIV strains of treated and treatment-naive HIV-1 infectious patients in Hubei province]. At the same time, novel RT mutations F214L might be associated with HAART or some other drugs. 2007 Zhonghua liu xing bing xue za zhi Abstract HIV F214L 37 42 RT 24 26 18396668 [Study on genotypic resistance mutations to antiretroviral drugs on HIV strains of treated and treatment-naive HIV-1 infectious patients in Hubei province]. F214L was positively associated with HAART treatment (P = 0.03). 2007 Zhonghua liu xing bing xue za zhi Abstract HIV F214L 0 5 18396668 [Study on genotypic resistance mutations to antiretroviral drugs on HIV strains of treated and treatment-naive HIV-1 infectious patients in Hubei province]. Some protease (PR) drug-resistant mutations were found in these samples, such as D30N (2.27%), D30G (2.27%), M46I (4.55%), M46N (2.27%), I47V (4.55%), I84V (4.55%), I84L (2.27%), N88S (2.27%) and L90S (2.27%) that all belonged to major drug-resistant but A71T (29.55%) belonged to minor resistance mutations Five treated patients were detected having mutations associated RT drug resistance: M41L (5.26%), A62V (5.26%),D67N (5.26%), L210W (5.26%), T215Y (15.79%); K103E (5.26%), K103N (10.53%), Y181C (5.26%), G190A (5.26%), K238N (5.26%), while five treatment-naive patients were detected to have had mutations associated RT drug resistance M184V (4%), K65N (4%), Y115M (4%), F116L (4%), M184I (4%), V179D (4%), G190R (4%).Some additional mutations were detected in RT whose role involve in drug resistance still remained unknown. 2007 Zhonghua liu xing bing xue za zhi Abstract HIV D67N;A62V;A71T;D30G;D30N;F116L;G190A;G190R;I47V;I84L;I84V;K103E;K103N;K238N;K65N;L210W;L90S;M184I;M184V;M41L;M46I;M46N;N88S;T215Y;V179D;Y115M;Y181C 419;406;255;95;81;677;510;713;137;165;151;464;479;525;654;433;196;689;642;392;109;123;179;448;701;665;495 423;410;259;99;85;682;515;718;141;169;155;469;484;530;658;438;200;694;647;396;113;127;183;453;706;670;500 PR;PR;RT;RT;RT 5;15;372;623;767 13;17;374;625;769 18419429 Entecavir therapy induces de novo HIV reverse-transcriptase M184V mutation in an antiretroviral therapy-naive patient. After 26 weeks of entecavir therapy, the M184V mutation dominated the plasma viral population. 2008 Clinical infectious diseases Abstract HIV M184V 41 46 18419429 Entecavir therapy induces de novo HIV reverse-transcriptase M184V mutation in an antiretroviral therapy-naive patient. This guideline was revised in 2007 because of a report showing that the M184V mutation was selected in an hepatitis B virus and HIV-coinfected patient previously treated with lamivudine. 2008 Clinical infectious diseases Abstract HIV M184V 72 77 18419495 Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa. The most common mutation was M184V/I (64.3% of patients); K103N was present in virus from 51.3%, and V106M was present in virus from 19.1%. 2008 Clinical infectious diseases Abstract HIV K103N;M184I;M184V;V106M 58;29;29;101 63;36;36;106 18419549 Specific enfuvirtide-associated mutational pathways in HIV-1 Gp41 are significantly correlated with an increase in CD4(+) cell count, despite virological failure. In contrast, T268A localizes in the gp41 calmodulin-binding domain responsible for gp41-induced CD4(+) T lymphocyte apoptosis. 2008 The Journal of infectious diseases Abstract HIV T268A 13 18 gp41;gp41 36;83 40;87 18419549 Specific enfuvirtide-associated mutational pathways in HIV-1 Gp41 are significantly correlated with an increase in CD4(+) cell count, despite virological failure. Residues 38 and 18 are located complementarily to each other in the Rev-responsive element, whereas analysis of molecular dynamics showed that the copresence of [V38A + N140 I] abolishes the interaction between residue 38 and 145 important for stabilization of the 6-helix bundle. 2008 The Journal of infectious diseases Abstract HIV N140I;V38A 169;162 175;166 Rev 68 71 18419549 Specific enfuvirtide-associated mutational pathways in HIV-1 Gp41 are significantly correlated with an increase in CD4(+) cell count, despite virological failure. The ENF-associated clusters [V38A + N140I ] and [V 38A +T18A ] significantly correlated with an increase in CD4 cell count at week 48 ( an increase from baseline of 112 and 209 cells/microL, respectively), whereas [Q40H + L45M + 268A] significantly correlated with a decrease in CD4 cell count (-53 cells/microL), without a change in the level of viremia. 2008 The Journal of infectious diseases Abstract HIV L45M;N140I;Q40H;T18A;V38A;V38A 222;36;215;56;29;49 226;41;219;60;33;54 18426195 Combination of non-natural D-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV protease inhibitors have high efficacy in mutant HIV. Interestingly, anti-HIV activity of all the D-amino acid-introduced inhibitors was remarkably enhanced in their anti-HIV activities against a Nelfinavir-resistant clone, which has a D30N mutation in the protease, over that of the wild-type strain. 2008 Journal of medicinal chemistry Abstract HIV D30N 182 186 PR 203 211 18426370 Changing patterns in HIV reverse transcriptase resistance mutations after availability of tenofovir. Assessment of 1177 human immunodeficiency virus (HIV) resistance genotypes at an HIV/AIDS clinic showed a decrease in the incidence of the K65R mutation, from 15.2% of isolates during the period 2002-2004 to 2.7% of isolates during the period 2005-2006 (P < .001), despite elevated and stable rates of tenofovir use. 2008 Clinical infectious diseases Abstract HIV K65R 139 143 AIDS 85 89 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. BACKGROUND: The human immunodeficiency virus type 1 reverse-transcriptase mutation K65R is a single-point mutation that has become more frequent after increased use of tenofovir disoproxil fumarate (TDF). 2008 Clinical infectious diseases Abstract HIV K65R 83 87 RT 52 73 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. CONCLUSIONS: In settings where thymidine analogue mutations are less likely to be present, such as at start of first-line therapy or after extended treatment interruptions, combinations of TDF with other K65R-inducing components or with efavirenz or nevirapine may carry an enhanced risk of the emergence of K65R. 2008 Clinical infectious diseases Abstract HIV K65R;K65R 204;308 208;312 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. METHODS: A total of 222 patients with genotypic resistance tests performed while receiving treatment with TDF-containing regimens were stratified by detectability of K65R (K65R group, 42 patients; undetected K65R group, 180 patients). 2008 Clinical infectious diseases Abstract HIV K65R;K65R;K65R 166;172;208 170;177;212 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. Proportions of patients attaining human immunodeficiency virus type 1 loads <50 copies/mL after 24 weeks of continuous treatment were similar for the K65R group (44.1%; 95% confidence interval, 27.2%-62.1%) and the wild-type group (51.9%; 95% confidence interval, 42.0%-61.6%). 2008 Clinical infectious diseases Abstract HIV K65R 150 154 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. RESULTS: In an adjusted logistic regression, TDF treatment with nonnucleoside reverse-transcriptase inhibitors and/or didanosine was associated with the emergence of K65R, whereas the presence of any of the thymidine analogue mutations D67N, K70R, T215F, or K219E/Q was protective. 2008 Clinical infectious diseases Abstract HIV D67N;K219E;K219Q;K65R;K70R;T215F 236;258;258;166;242;248 240;265;265;170;246;253 NNRTI 64 99 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. Salvage therapy after TDF treatment was started for 36 patients with K65R and for 118 patients from the wild-type group. 2008 Clinical infectious diseases Abstract HIV K65R 69 73 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. The finding of a distinct mutational pattern selected by treatment with TDF and efavirenz suggests a potential fitness interaction between K65R and nonnucleoside reverse-transcriptase inhibitor-induced mutations. 2008 Clinical infectious diseases Abstract HIV K65R 139 143 NNRTI 148 183 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. The previously undescribed mutational pattern K65R/G190S/Y181C was observed in 6 of 21 patients treated with efavirenz and TDF. 2008 Clinical infectious diseases Abstract HIV G190S;K65R;Y181C 51;46;57 56;50;62 18444871 Factors associated with the emergence of K65R in patients with HIV-1 infection treated with combination antiretroviral therapy containing tenofovir. We aimed to identify predictors for the emergence of K65R, using clinical data and genotypic resistance tests from the Swiss HIV Cohort Study. 2008 Clinical infectious diseases Abstract HIV K65R 53 57 18448538 Comparison of G-to-A mutation frequencies induced by APOBEC3 proteins in H9 cells and peripheral blood mononuclear cells in the context of impaired processivities of drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants. The frequencies of G-to-A mutations were increased after infection with the M184I virus variant. 2008 Journal of virology Abstract HIV M184I 76 81 18448538 Comparison of G-to-A mutation frequencies induced by APOBEC3 proteins in H9 cells and peripheral blood mononuclear cells in the context of impaired processivities of drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants. The M184V mutation led to G-to-A mutation frequencies that were similar to those of the wild-type RT in H9 cells and PBMCs. 2008 Journal of virology Abstract HIV M184V 4 9 RT 98 100 18448538 Comparison of G-to-A mutation frequencies induced by APOBEC3 proteins in H9 cells and peripheral blood mononuclear cells in the context of impaired processivities of drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants. This effect was augmented when using the K65R+M184V virus variant (P < 0.001). 2008 Journal of virology Abstract HIV K65R;M184V 41;46 45;51 18448538 Comparison of G-to-A mutation frequencies induced by APOBEC3 proteins in H9 cells and peripheral blood mononuclear cells in the context of impaired processivities of drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants. Wild-type RT or the M184V, M184I, and K65R+M184V RT variants, which are increasingly impaired in their processivities, were used in the context of a vif-deficient molecular HIV-1 clone to infect H9 cells and peripheral blood mononuclear cells (PBMCs). 2008 Journal of virology Abstract HIV K65R;M184I;M184V;M184V 38;27;20;43 42;32;25;48 Vif;RT;RT 149;10;49 152;12;51 18453854 The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. BACKGROUND: Entecavir, an antiviral with potent anti-hepatitis B virus activity, was recently shown to have anti-HIV activity in three patients and the ability to select for the lamivudine-resistant HIV polymerase mutation M184V in a patient with prior antiretroviral therapy. 2008 AIDS (London, England) Abstract HIV M184V 223 228 Pol 203 213 18453854 The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. CONCLUSION: Entecavir monotherapy in HIV-hepatitis B virus coinfected patients, including antiretroviral therapy-naive patients, has significant anti-HIV activity and can result in the development of the M184V variant. 2008 AIDS (London, England) Abstract HIV M184V 204 209 18453854 The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. OBJECTIVES: To further characterize entecavir's anti-HIV activity and identify risk factors for selection of the M184V. 2008 AIDS (London, England) Abstract HIV M184V 113 118 18453854 The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. Of the remaining four patients, two had the M184V detected prior to entecavir therapy and the other two had wild-type HIV. 2008 AIDS (London, England) Abstract HIV M184V 44 49 18453854 The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. Risk factors for the emergence of the M184V mutation were a decline in hepatitis B virus DNA (P = 0.04) and duration of entecavir use (P = 0.05). 2008 AIDS (London, England) Abstract HIV M184V 38 43 18453854 The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. The M184V mutation emerged in six patients receiving entecavir, including three antiretroviral therapy-naive patients. 2008 AIDS (London, England) Abstract HIV M184V 4 9 18453854 The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. Variables associated with development of the M184V were determined by univariate analysis. 2008 AIDS (London, England) Abstract HIV M184V 45 50 18457904 QSAR studies for diarylpyrimidines against HIV-1 reverse transcriptase wild-type and mutant strains. Additionally, the results indicate that logP plays a vital role in the prediction of the activity of DAPYs, and the cyano group on the left wing is important for inhibiting the mutant forms L100I and Y188N. 2009 European journal of medicinal chemistry Abstract HIV L100I;Y188N 190;200 195;205 18457904 QSAR studies for diarylpyrimidines against HIV-1 reverse transcriptase wild-type and mutant strains. For the activity values against HIV-1 RT wild-type and mutant strains (L100I, Y181C and Y188N) of 34 diarylpyrimidines (DAPYs) taken from literature, multiple linear regression analysis and the crossvalidation of Leave-One-Out method are carried out against the activity values with the hydrophobicity index logP, the modified steric parameter L(Y), the Muliken charge of nitrogen atom on the right wing N(C) and the indicator index I for the substituents R(3)' and R(1) on the left wing, and four good QSAR models are established: R=0.8211(N=34), R=0.8599 (N=33), R=0.8711(N=30) and R=0.9079 (N=29) for the cases of wild type, and mutant strain forms L100I, Y181C and Y188N, respectively. 2009 European journal of medicinal chemistry Abstract HIV L100I;L100I;Y181C;Y181C;Y188N;Y188N 71;652;78;659;88;669 76;657;83;664;93;674 RT 38 40 18462083 Genotypic susceptibility scores and HIV type 1 RNA responses in treatment-experienced subjects with HIV type 1 infection. Certain NNRTI-associated mutations, such as K103N, were rapidly selected in the absence of NRTIs. 2008 AIDS research and human retroviruses Abstract HIV K103N 44 49 NNRTI;NRTI 8;91 13;96 18462084 Drug-resistance mutations number and K70R or T215Y/F substitutions predict treatment resumption during guided treatment interruptions. A history of monotherapy or dual therapy, accumulation of three or more key DRMs in the HIV-1 polymerase, and/or the presence of substitutions K70R or T215F/Y were associated with shorter time off therapy during GTI. 2008 AIDS research and human retroviruses Abstract HIV K70R;T215F;T215Y 143;151;151 147;158;158 Pol 94 104 18462084 Drug-resistance mutations number and K70R or T215Y/F substitutions predict treatment resumption during guided treatment interruptions. Multivariate analyses adjusted by nadir CD4(+) counts supported the presence of DRMs in plasma HIV-1 RNA, and specifically the K70R or T215F/Y, as potent predictors of time off therapy. 2008 AIDS research and human retroviruses Abstract HIV K70R;T215F;T215Y 127;135;135 131;142;142 18462084 Drug-resistance mutations number and K70R or T215Y/F substitutions predict treatment resumption during guided treatment interruptions. Regardless of the number of DRMs, the presence of K70R or T215F/Y predicted the shortest TI time. 2008 AIDS research and human retroviruses Abstract HIV K70R;T215F;T215Y 50;58;58 54;65;65 18465760 Substrate-induced stable enzyme-inhibitor complex formation allows tight binding of novel 2-aminopyrimidin-4(3H)-ones to drug-resistant HIV-1 reverse transcriptase mutants. Interestingly, one compound showed dissociation rates from the ternary complex with RT mutants K103N and Y181I 10-20-fold slower than from the corresponding complex with wild-type RT. 2008 ChemMedChem Abstract HIV K103N;Y181I 95;105 100;110 RT;RT 84;180 86;182 18465760 Substrate-induced stable enzyme-inhibitor complex formation allows tight binding of novel 2-aminopyrimidin-4(3H)-ones to drug-resistant HIV-1 reverse transcriptase mutants. These compounds are highly active against both wild-type HIV-1 and the K103N, Y181C, and Y188L mutant strains. 2008 ChemMedChem Abstract HIV K103N;Y181C;Y188L 71;78;89 76;83;94 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. BACKGROUND: The HIV-1 protease mutation I50 L causes atazanavir resistance but increases susceptibility to other PIs. 2008 Journal of clinical virology Abstract HIV I50L 40 45 PR;PI 22;113 30;116 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. CONCLUSIONS: The PI mutation I50 L causes clinically relevant resistance and increased susceptibility to atazanavir and other PIs respectively. 2008 Journal of clinical virology Abstract HIV I50L 29 34 PI;PI 17;126 19;129 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. I50 L caused resistance to atazanavir in all 31 mutation contexts, but was associated with higher susceptibility for other PIs. 2008 Journal of clinical virology Abstract HIV I50L 0 5 PI 123 126 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. I50 L-associated shifts in FC were evaluated using drug-specific CCOs. 2008 Journal of clinical virology Abstract HIV I50L 0 5 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. OBJECTIVE: To evaluate I50 L's effect on susceptibility to 8 PIs, in a large genotype database. 2008 Journal of clinical virology Abstract HIV I50L 23 28 PI 61 64 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. RESULTS: We selected 307 and 37098 samples with and without I50 L. 2008 Journal of clinical virology Abstract HIV I50L 60 65 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. STUDY DESIGN: I50 L containing routine clinical isolate samples in Virco's genotype database were paired with samples having like patterns (or profiles) of IAS-USA-defined primary PI mutations, but lacking I50 L. 2008 Journal of clinical virology Abstract HIV I50L;I50L 14;206 19;211 PI 180 182 18472298 The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts. The largest I50 L-associated shifts in median predicted FC were: 1.2 to 42.4 (atazanavir), 10.2 to 3.2 (amprenavir), 3.3 to 0.5 (darunavir), 13 to 0.5 (indinavir), 34.9 to 1.3 (lopinavir), 22.3 to 1.3 (nelfinavir), 5.2 to 0.3 (saquinavir) and 29.9 to 5.2 (tipranavir). 2008 Journal of clinical virology Abstract HIV I50L 12 17 18480092 Novel macromolecular inhibitors of human immunodeficiency virus-1 protease. Based on in silico studies, two mutant PRs harboring hydrophilic mutations, capable of forming favorable inter- and intra-subunit interactions, were selected: PR(RE) containing Asp25Arg and Gly49Glu mutations, and PR(RER) containing an additional Ile50Arg mutation. 2008 Protein engineering, design & selection Abstract HIV D25R;G49E;I50R 177;190;247 185;198;255 Asp;PR;PR;PR 177;39;159;214 180;42;161;216 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. Human immunodeficiency virus type 1 (HIV-1) viruses with C/S/D/E at 215 codon of the reverse transcriptase (RT) have been associated with the T215Y/F HIV-1 resistant viruses transmission to naive patients. 2008 Virus research Abstract HIV T215F;T215Y 142;142 149;149 RT;RT 85;108 106;110 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. Selection of resistance mutations was not observed in viral quasispecies of the T215V virus after serial passages in culture in presence of increasing concentrations of AZT, ddI or d4T. 2008 Virus research Abstract HIV T215V 80 85 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. The T215V virus replicated as efficiently as the wild-type (T215) without antivirals and in the presence of AZT or ddI. 2008 Virus research Abstract HIV T215V 4 9 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. The T215V virus showed higher replicative capacity than the wild-type and a 4.3-fold increase in the IC(50) values in cultures with d4T. 2008 Virus research Abstract HIV T215V 4 9 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. The uncommon T215V mutation was detected in DNA proviral samples of a treatment-naive patient. 2008 Virus research Abstract HIV T215V 13 18 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. This work demonstrates that the T215V mutation decreases the susceptibility of HIV-1 to d4T, and consequently, it could compromise the response to regimens containing this antiviral. 2008 Virus research Abstract HIV T215V 32 37 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. Virus T215V was obtained after cloning the patient-RT into a molecular clone. 2008 Virus research Abstract HIV T215V 6 11 RT 51 53 18482778 An HIV-1 215V mutant shows increased phenotypic resistance to d4T. Wild-type (T215) and resistant (T215F) clones, were obtained in T215V clone by "in vitro" site-directed mutagenesis. 2008 Virus research Abstract HIV T215F;T215V 32;64 37;69 18483694 Profile of drug resistance mutations among HIV-1-infected Tunisian subjects failing antiretroviral therapy. In the RT gene, resistance to nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) were recognized in 66.25 and 37.5%, respectively, with M184V, T215Y and K103N being the codons most frequently involved. 2008 Archives of virology Abstract HIV K103N;M184V;T215Y 177;160;167 182;165;172 NNRTI;NRTI;RT;RT;RT 97;56;7;41;82 103;61;9;43;84 18484978 Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. Better CD4 outcomes were seen in patients without M41L (P=0.04) or with baseline VL<10,000 copies/mL (P=0.01). 2008 HIV medicine Abstract HIV M41L 50 54 18484978 Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. Lower probability of achieving VL<400 copies/mL was associated with D67N (P=0.007), D67N/M41L (P=0.01), > or =3 TAMs (P=0.07) and VL>10 000 copies/mL (P=0.01). 2008 HIV medicine Abstract HIV D67N;D67N;M41L 68;84;89 72;88;93 18484978 Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. METHODS: Pilot analysis of highly experienced patients (n=28), with > or =1 thymidine-associated mutation (TAM) and the M184V mutation. 2008 HIV medicine Abstract HIV M184V 120 125 18484978 Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. 2008 HIV medicine Abstract HIV K65R;L74V;Y181C 60;69;53 64;73;58 18484978 Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. There was no evolution in RT mutations, TAMs, accessory mutations or K65R. 2008 HIV medicine Abstract HIV K65R 69 73 RT 26 28 18487070 2'-deoxy-4'-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants. EFdA retains potency toward many HIV-1 resistant strains, including the multi-drug resistant clone HIV-1A62V/V75I/F77L/F116Y/Q151M. 2008 The international journal of biochemistry & cell biology Abstract HIV A62V;F116Y;F77L;Q151M;V75I 104;119;114;125;109 108;124;118;130;113 18487070 2'-deoxy-4'-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants. Moderate decrease in susceptibility to EFdA is conferred by a combination of three RT mutations (I142V, T165R, and M184V) that result in a significant decrease of viral fitness. 2008 The international journal of biochemistry & cell biology Abstract HIV I142V;M184V;T165R 97;115;104 102;120;109 RT 83 85 18487070 2'-deoxy-4'-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants. Molecular modeling analysis suggests that the M184V/I substitutions may reduce anti-HIV activity of EFdA through steric hindrance between its 4'-ethynyl moiety and the V/I184 beta-branched side chains. 2008 The international journal of biochemistry & cell biology Abstract HIV M184I;M184V 46;46 53;53 18495769 Transmission of human immunodeficiency virus type 1 from a patient who developed AIDS to an elite suppressor. Isolates from both patients were replication competent and contained the T242N escape mutation in Gag, which is known to decrease viral fitness. 2008 Journal of virology Abstract HIV T242N 73 78 Gag 98 101 18502646 Parallel one-pot synthesis and structure-activity relationship study of symmetric formimidoester disulfides as a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Compounds 19 and 33 were active at micromolar concentrations against the clinically relevant Y181C and/or K103R resistant mutants. 2008 Bioorganic & medicinal chemistry Abstract HIV K103R;Y181C 106;93 111;98 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. HIV-1 with K65R or L74V/I alone were fully susceptible to zidovudine and stavudine. 2008 Antiviral therapy Abstract HIV K65R;L74I;L74V 11;19;19 15;25;25 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. K65R was associated with reduced susceptibility to tenofovir, didanosine, abacavir and lamivudine; L74V/I was associated with reduced susceptibility to abacavir and didanosine. 2008 Antiviral therapy Abstract HIV L74I;L74V;K65R 99;99;0 105;105;4 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. K65R was detected in 3.3% of isolates and its frequency remained stable from 2003 to 2006, similar to trends observed for other NAMs. 2008 Antiviral therapy Abstract HIV K65R 0 4 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. L74V/I was detected in 11% of isolates. 2008 Antiviral therapy Abstract HIV L74I;L74V 0;0 6;6 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. Other NAMs commonly associated with K65R were A62V, S68G and Y115F; their NRTI susceptibilities were similar to those of viruses containing K65R alone. 2008 Antiviral therapy Abstract HIV A62V;K65R;K65R;S68G;Y115F 46;36;140;52;61 50;40;144;56;66 NRTI 74 78 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. RESULTS: Thymidine analogue mutations (TAMs) and M184V were the most commonly observed NAMs (>25%). 2008 Antiviral therapy Abstract HIV M184V 49 54 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. TAMs were rarely observed in combination with K65R, but frequently associated with L74V/I. 2008 Antiviral therapy Abstract HIV K65R;L74I;L74V 46;83;83 50;89;89 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. The addition of M184V to either K65R or L74V/I improved susceptibility to tenofovir, zidovudine and stavudine, but reduced susceptibility to abacavir, didanosine and lamivudine. 2008 Antiviral therapy Abstract HIV K65R;L74I;L74V;M184V 32;40;40;16 36;46;46;21 18505170 Prevalence, genotypic associations and phenotypic characterization of K65R, L74V and other HIV-1 RT resistance mutations in a commercial database. The replication capacity for HIV-1 with M184V/I or K65R was significantly reduced compared with wild-type (median 68%/ and 72%, respectively; P<0.0001), whereas replication capacity for HIV-1 with L74V or TAMs was not significantly reduced (88% and 97%, respectively). 2008 Antiviral therapy Abstract HIV K65R;L74V;M184I;M184V 51;197;40;40 55;201;47;47 18505178 Virological response to darunavir/ritonavir-based regimens in antiretroviral-experienced patients (PREDIZISTA study). We determined the genotypic score I13V+V32I+L33F/I/V+E35D+ M361/L/V+I47V+F53L+I62V. 2008 Antiviral therapy Abstract HIV E35D;F53L;I13V;I47V;I62V;L33F;L33I;L33V;M361L;M361V;V32I 53;73;34;68;78;44;44;44;59;59;39 57;77;38;72;82;52;52;52;67;67;43 18507398 Impact of the enfuvirtide resistance mutation N43D and the associated baseline polymorphism E137K on peptide sensitivity and six-helix bundle structure. N43D, a common ENF resistance mutation, was found in in vitro assays to cause a 5-50-fold in antiviral activity. 2008 Biochemistry Abstract HIV N43D 0 4 18507398 Impact of the enfuvirtide resistance mutation N43D and the associated baseline polymorphism E137K on peptide sensitivity and six-helix bundle structure. The E137K polymorphism, generally present at baseline in patients who develop N43D, partially compensates for the loss of stability, and we show that these residues likely form an ion pair. 2008 Biochemistry Abstract HIV E137K;N43D 4;78 9;82 18507527 Study of the genotypic resistant pattern in HIV-infected women and children from rural west Cameroon. Mutations associated with nucleoside RT inhibitors (M184V in one case and V118I in four cases) were found in five samples, despite being derived from ARV-naive patients. 2008 AIDS research and human retroviruses Abstract HIV M184V;V118I 52;74 58;79 RT 37 39 18507527 Study of the genotypic resistant pattern in HIV-infected women and children from rural west Cameroon. Other mutations frequently detected were K20I, L63P, H69K, and I13V. 2008 AIDS research and human retroviruses Abstract HIV H69K;I13V;K20I;L63P 53;63;41;47 57;67;45;51 18507527 Study of the genotypic resistant pattern in HIV-infected women and children from rural west Cameroon. The secondary mutations showed the typical protease inhibitor resistance-associated pattern for non-subtype B viruses, M36I being the predominant mutation (92.5% in women, 100% in babies). 2008 AIDS research and human retroviruses Abstract HIV M36I 119 123 PR 43 51 18524771 Assembly with the Cul4A-DDB1DCAF1 ubiquitin ligase protects HIV-1 Vpr from proteasomal degradation. DCAF1 overexpression stabilizes wild-type Vpr and leads to its cytoplasmic accumulation, whereas it has no effect on the Vpr(Q65R) mutant. 2008 The Journal of biological chemistry Abstract HIV Q65R 125 129 Vpr;Vpr 42;121 45;124 18524771 Assembly with the Cul4A-DDB1DCAF1 ubiquitin ligase protects HIV-1 Vpr from proteasomal degradation. We show that the Vpr(Q65R) mutant, which is defective in DCAF1 binding, undergoes proteasome-mediated degradation at a higher rate than wild-type Vpr. 2008 The Journal of biological chemistry Abstract HIV Q65R 21 25 Vpr;Vpr 17;146 20;149 18541223 Selective targeting of the HIV-1 reverse transcriptase catalytic complex through interaction with the "primer grip" region by pyrrolobenzoxazepinone non-nucleoside inhibitors correlates with increased activity towards drug-resistant mutants. Our kinetic analysis indicates that the ability of PBOs to selectively target the catalytic ternary complex of RT with its substrates directly correlates with greatly reduced sensitivity to NNRTIs-resistance mutations, particularly the K103N substitution. 2008 Biochemical pharmacology Abstract HIV K103N 236 241 NNRTI;RT 190;111 196;113 18541726 Preclinical evaluation of 1H-benzylindole derivatives as novel human immunodeficiency virus integrase strand transfer inhibitors. The mutations T66I and Q146K were present in integrase. 2008 Antimicrobial agents and chemotherapy Abstract HIV Q146K;T66I 23;14 28;18 IN 45 54 18543336 Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis. Histological studies show an attenuation of motor neuron loss and a decrease in the number of cleaved caspase 9-, cleaved caspase 3-, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in the lumbar cords of TAT-modified Bcl-X(L)-treated G93A mice. 2008 Journal of neuroscience research Abstract HIV G93A 284 288 Tat 254 257 18543336 Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis. We have constructed a powerful antiapoptotic modified Bcl-X(L) protein (originally constructed from Bcl-X(L)) fused with PTD derived from TAT (TAT-modified Bcl-X(L)), and, to examine its clinical effectiveness in a mouse model of familial amyotrophic lateral sclerosis (ALS), transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) bearing a G93A mutation were treated by intrathecal infusion of TAT-modified Bcl-X(L). 2008 Journal of neuroscience research Abstract HIV G93A 353 357 Tat;Tat;Tat 138;143;407 141;146;410 18544024 HIV type 2 protease, reverse transcriptase, and envelope viral variation in the PBMC and genital tract of ARV-naive women in Senegal. In another subject, the reverse transcriptase A62V mutation was also found in CVL-RNA but not PBMCs. 2008 AIDS research and human retroviruses Abstract HIV A62V 46 50 RT 24 45 18544024 HIV type 2 protease, reverse transcriptase, and envelope viral variation in the PBMC and genital tract of ARV-naive women in Senegal. One subject had the HIV-2 reverse transcriptase M184I mutation in CVL DNA (but not PBMCs) that is known to confer 3TC/FTC resistance in HIV-2. 2008 AIDS research and human retroviruses Abstract HIV M184I 48 53 RT 26 47 18544024 HIV type 2 protease, reverse transcriptase, and envelope viral variation in the PBMC and genital tract of ARV-naive women in Senegal. Two subjects had protease mutations (T77I and I64V) in genital tract samples that were not found in PBMCs. 2008 AIDS research and human retroviruses Abstract HIV I64V;T77I 46;37 50;42 PR 17 25 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. In addition, the G48E and G48E/V82A site-directed mutants were associated with a decrease in fitness, whereas a reversion to the wild type at position 48 was observed in vitro. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48E;G48E;V82A 17;26;31 21;30;35 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. In summary, our results demonstrate that the G48E substitution, when introduced in the context of an HIV-1 subtype B strain, is highly unstable and gives rise to viruses with a poor replicative fitness in vitro. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48E 45 49 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. Phenotypic analysis of protease inhibitor (PI) susceptibility showed that the G48E site-directed mutant, when introduced into an NL4-3 HIV-1 PR backbone, was slightly resistant to SQV (2-fold when compared with the wild-type virus). 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48E 78 82 PR;PI;PR 23;43;141 31;45;143 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. red fluorescent protein-expressing viruses showed that the replicative fitness of the G48E virus was reduced to 55% compared with the parental NL4-3 virus. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48E 86 90 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. These simulations documented that the G48E mutant interacted with PI resistance mutations (M46I, I54V, Q58E, and L63P) and with natural polymorphisms specific to subtype A1 (E35D, M36I, and R57K) that were present in the patient's virus. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E35D;G48E;I54V;L63P;M36I;M46I;Q58E;R57K 174;38;97;113;180;91;103;190 178;42;101;117;184;95;107;194 PI 66 68 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. We hypothesize that the polymorphisms contained in the PR flap regions of the patient's virus may compensate for the presence of G48E, possibly by restoring the flexibility of the PR flaps. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48E 129 133 PR;PR 55;180 57;182 18545158 Impact on replicative fitness of the G48E substitution in the protease of HIV-1: an in vitro and in silico evaluation. We observed an unusual glycine-to-glutamate substitution at protease (PR) residue position 48 (G48E) in an African patient infected with a subtype A1 HIV-1 strain failing a saquinavir-containing regimen. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48E 95 99 PR;PR 60;70 68;72 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Here, we focused on connection mutations N348I and A360V that are frequently observed in clinical samples of treatment-experienced patients. 2008 The Journal of biological chemistry Abstract HIV A360V;N348I 51;41 56;46 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The TAMs/N348I/A360V mutant accumulates transiently formed, shorter hybrids that can rebind to RT before the template is irreversibly degraded. 2008 The Journal of biological chemistry Abstract HIV A360V;N348I 15;9 20;14 RT 95 97 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. These hybrids dissociate selectively from the RNase H-competent complex, whereas binding in the polymerase-competent mode is either not affected with N348I or modestly improved with A360V. 2008 The Journal of biological chemistry Abstract HIV A360V;N348I 182;150 187;155 Pol 96 106 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. We show that both N348I and A360V, in combination with TAMs, decrease the efficiency of RNase H cleavage and increase excision of AZT in the presence of the pyrophosphate donor ATP. 2008 The Journal of biological chemistry Abstract HIV A360V;N348I 28;18 33;23 18550661 Phylogenetic and genetic analysis of feline immunodeficiency virus gag, pol, and env genes from domestic cats undergoing nucleoside reverse transcriptase inhibitor treatment or treatment-naive cats in Rio de Janeiro, Brazil. These signatures were comparable to K65R and K70R thymidine-associated mutations found in the HIV-1 HXB2 counterpart. 2008 Journal of virology Abstract HIV K65R;K70R 36;45 40;49 18550661 Phylogenetic and genetic analysis of feline immunodeficiency virus gag, pol, and env genes from domestic cats undergoing nucleoside reverse transcriptase inhibitor treatment or treatment-naive cats in Rio de Janeiro, Brazil. This finding strongly suggests a position correlation between the mutations found in FIV and the K65R and K70R substitutions from drug-resistant HIV-1 strains. 2008 Journal of virology Abstract HIV K65R;K70R 97;106 101;110 18552344 HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). 2008 The Journal of antimicrobial chemotherapy Abstract HIV L45M;N42T;N43D;Q40H;V38A;V38M 53;38;44;32;24;24 57;42;48;36;30;30 18556706 Evolution of genetic diversity and drug resistance mutations in HIV-1 among untreated patients from Mali between 2005 and 2006. Resistance mutations found in RT and PR genes are in agreement with the highly active antiretroviral therapy regimen available in Mali, except for V90I, V106I and A98G mutations which are associated with etravirine resistance, but polymorphic in non-B subtypes. 2008 The Journal of antimicrobial chemotherapy Abstract HIV A98G;V106I;V90I 163;153;147 167;158;151 PR;RT 37;30 39;32 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. Furthermore, we analyzed possible interaction of the I47A mutation with secondary mutations V32I and I54V. 2008 Protein science Abstract HIV I47A;I54V;V32I 53;101;92 57;105;96 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. In this study, we show that recombinant PR containing a single I47A substitution has the inhibition constant (K(i) ) value for lopinavir by two orders of magnitude higher than for the wild-type PR. 2008 Protein science Abstract HIV I47A 63 67 PR;PR 40;194 42;196 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. The addition of the I47A substitution to the background of a multiply mutated PR species from an AIDS patient showed a three-order-of-magnitude increase in K(i) in vitro relative to the patient PR without the I47A mutation. 2008 Protein science Abstract HIV I47A;I47A 20;209 24;213 PR;PR 78;194 80;196 AIDS 97 101 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. The crystal structure of I47A PR in complex with LPV showed the loss of van der Waals interactions in the S2/S2' subsites. 2008 Protein science Abstract HIV I47A 25 29 PR 30 32 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. The crystal structure of the I47A/I54V PR double mutant in complex with LPV shows that the I54V mutation leads to a compaction of the flap, and molecular modeling suggests that the introduction of the I54V mutation indirectly affects the strain of the bound inhibitor in the PR binding cleft. 2008 Protein science Abstract HIV I47A;I54V;I54V;I54V 29;34;91;201 33;38;95;205 PR;PR 39;275 41;277 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. This is caused by the loss of three side-chain methyl groups due to the I47A substitution and by structural changes in the A47 main chain that lead to structural changes in the flap antiparallel beta-strand. 2008 Protein science Abstract HIV I47A 72 76 18560011 Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavir. We show that both mutations in combination with I47A synergistically increase the relative resistance to LPV in vitro. 2008 Protein science Abstract HIV I47A 48 52 18572749 Enfuvirtide cerebrospinal fluid (CSF) pharmacokinetics and potential use in defining CSF HIV-1 origin. In one individual, who developed a transient increase in CSF HIV-1 RNA, seven of seven CSF and plasma clones had identical enfuvirtide resistance-associated V38A mutations, suggesting that the CSF quasispecies derived from that of blood. 2008 Antiviral therapy Abstract HIV V38A 157 161 18573290 Pathogenicity and immunogenicity of recombinant Tiantan Vaccinia Virus with deleted C12L and A53R genes. Furthermore, VTKgpe with A53R and C12L gene deletion retains the high immunogenicity of the parental virus to elicit strong humoral and cellular responses to the HIV target genes despite the remarkable attenuation. 2008 Vaccine Abstract HIV A53R;C12L 25;34 29;38 18573290 Pathogenicity and immunogenicity of recombinant Tiantan Vaccinia Virus with deleted C12L and A53R genes. Notably, C12L deletion mutant attenuated the skin virulence of parental virus by as high as approximate 2 logs. 2008 Vaccine Abstract HIV C12L 9 13 18573290 Pathogenicity and immunogenicity of recombinant Tiantan Vaccinia Virus with deleted C12L and A53R genes. To develop a safer and more effective TV-based vector, we constructed C12L (vIL-18 binding protein) and A53R (vTNF receptor homolog) gene-deleted mutants which are based on parental TV and VTKgpe (TV expressing HIV gagpol and env gene), respectively. 2008 Vaccine Abstract HIV A53R;C12L 104;70 108;74 Env 226 229 18573931 Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects. Despite the presence of viral variants with a lysine-to-arginine substitution at codon 65 (K65R) of RT in all 28 SIV-infected animals, 6 animals suppressed viremia to undetectable levels for as long as 12 years of TFV monotherapy. 2008 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R 91;46 95;89 RT 100 102 18575198 Antiretroviral drug resistance surveillance among drug-naive HIV-1-infected individuals in Gauteng Province, South Africa in 2002 and 2004. Of these, one had T69D and one had the K70R resistance mutation, to give a total of 2/48 (4.2%) participants with evidence of resistance mutations by genotyping. 2008 Antiviral therapy Abstract HIV K70R;T69D 39;18 43;22 18575198 Antiretroviral drug resistance surveillance among drug-naive HIV-1-infected individuals in Gauteng Province, South Africa in 2002 and 2004. One sample that was wild-type by genotyping was positive for K103N by AS-PCR. 2008 Antiviral therapy Abstract HIV K103N 61 66 18575198 Antiretroviral drug resistance surveillance among drug-naive HIV-1-infected individuals in Gauteng Province, South Africa in 2002 and 2004. Samples were also tested for the K103N mutation using a highly sensitive allele-specific real-time PCR assay (AS-PCR). 2008 Antiviral therapy Abstract HIV K103N 33 38 18575200 HIV drug resistance threshold survey using specimens from voluntary counselling and testing sites in Hanoi, Vietnam. Only 1 of 49 genotyped specimens had mutations associated with drug resistance (L74V and Y181C) in the reverse transcriptase gene, indicating that the prevalence of transmitted HIVDR to all drugs and drug classes evaluated was <5%. 2008 Antiviral therapy Abstract HIV L74V;Y181C 80;89 85;94 RT 103 124 18577511 Biochemical analysis of HIV-1 integrase variants resistant to strand transfer inhibitors. Finally, except for T66I, variant viruses harboring the resistance-inducing substitutions were defective for viral integration. 2008 The Journal of biological chemistry Abstract HIV T66I 20 24 18577511 Biochemical analysis of HIV-1 integrase variants resistant to strand transfer inhibitors. In the case of the Q148R variant, the origin of reduced compound affinity lies in alterations to the active site that reduce the binding of a catalytically essential magnesium ion. 2008 The Journal of biological chemistry Abstract HIV Q148R 19 24 18577511 Biochemical analysis of HIV-1 integrase variants resistant to strand transfer inhibitors. The Q148R variant was the most defective enzyme. 2008 The Journal of biological chemistry Abstract HIV Q148R 4 9 18580613 Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). 2008 AIDS (London, England) Abstract HIV Y181C 106 111 NNRTI 72 77 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. The proportion of women infected with variants with resistance mutations, the types of mutations detected, and the frequency and level of K103N were similar in the two groups of women at 6 weeks and 6 months post partum. 2008 The Journal of infectious diseases Abstract HIV K103N 138 143 18591263 Mechanisms of human immunodeficiency virus type 1 concerted integration related to strand transfer inhibition and drug resistance. Each mutant exhibited some degree of catalytic impairment relative to the activity of wild type IN, although the N155H mutant displayed near-wild-type IN activities. 2008 Antimicrobial agents and chemotherapy Abstract HIV N155H 113 118 IN;IN 96;151 98;153 18591263 Mechanisms of human immunodeficiency virus type 1 concerted integration related to strand transfer inhibition and drug resistance. The N155H mutation confers resistance to L-870,810 and potentiates susceptibility to L-841,411. 2008 Antimicrobial agents and chemotherapy Abstract HIV N155H 4 9 18591263 Mechanisms of human immunodeficiency virus type 1 concerted integration related to strand transfer inhibition and drug resistance. The resistance profiles indicated that the S153Y mutation potentiates susceptibility to L-870,810 and L-870,812, while the N155S mutation confers resistance to L-870,810 and L-870,812. 2008 Antimicrobial agents and chemotherapy Abstract HIV N155S;S153Y 123;43 128;48 18591263 Mechanisms of human immunodeficiency virus type 1 concerted integration related to strand transfer inhibition and drug resistance. The S153Y and N155S IN resistance mutants were selected with the diketo acid L-841,411, and the N155H mutant was selected with L-810,812. 2008 Antimicrobial agents and chemotherapy Abstract HIV N155H;N155S;S153Y 96;14;4 101;19;9 IN 20 22 18593351 Profile of primary resistance in HIV-1-infected treatment-naive individuals from Western India. The resistance mutation observed in the protease gene was V82A, whereas in the RT gene, M41L, D67N, M184V, and A98G were documented. 2008 AIDS research and human retroviruses Abstract HIV A98G;D67N;M184V;M41L;V82A 111;94;100;88;58 115;98;105;92;62 PR;RT 40;79 48;81 18596095 Analysis of natural sequence variation and covariation in human immunodeficiency virus type 1 integrase. The critical mutations that determine the resistance pathways to raltegravir and elvitegravir (N155H, Q148K/R/H, and E92Q) were either rare or absent from the 1,165-sequence data set. 2008 Journal of virology Abstract HIV E92Q;N155H;Q148H;Q148K;Q148R 117;95;102;102;102 121;100;111;111;111 18597484 Role of the HIV gp120 conserved domain 5 in processing and viral entry. In the case of the nonfunctional mutant P498A, the introduction of the SOS mutation (A501C/T601C) results in substantially increased envelope processing and a gain of function. 2008 Biochemistry Abstract HIV A501C;P498A;T601C 85;40;91 90;45;96 Env 133 141 18597484 Role of the HIV gp120 conserved domain 5 in processing and viral entry. With respect to the wild-type gp120, mutational effects on viral entry fall into three classes: (1) functional (V489A, E492A, P493A, T499A, K500A, K502A, R503A, R504A, V505A, and V506A; (2) nonfunctional (I491A, L494A, V496A, and P498A); (3) enhanced (K490A, G495A, and Q507A). 2008 Biochemistry Abstract HIV E492A;G495A;I491A;K490A;K500A;K502A;L494A;P493A;P498A;Q507A;R503A;R504A;T499A;V489A;V496A;V505A;V506A 119;259;205;252;140;147;212;126;230;270;154;161;133;112;219;168;179 124;264;210;257;145;152;217;131;235;275;159;166;138;117;224;173;184 gp120 30 35 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. PR(G48V) was about twofold less susceptible to SQV than to DRV, whereas the opposite was observed for PR(I50V). 2008 Journal of molecular biology Abstract HIV G48V;I50V 3;102 7;110 PR;PR 0;102 2;104 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The crystal structures of flap mutants PR(I50V) (PR with I50V mutation), PR(I54V) (PR with I54V mutation), and PR(I54M) (PR with I54M mutation) complexed with saquinavir (SQV) as well as PR(G48V) (PR with G48V mutation), PR(I54V), and PR(I54M) complexed with darunavir (DRV) were determined at resolutions of 1.05-1.40 A. 2008 Journal of molecular biology Abstract HIV G48V;G48V;I50V;I50V;I54M;I54M;I54M;I54V;I54V;I54V 187;205;39;57;111;129;235;73;91;221 195;209;47;61;119;133;243;81;95;229 PR;PR;PR;PR;PR;PR;PR;PR;PR;PR 39;49;73;83;111;121;187;197;221;235 41;51;75;85;113;123;189;199;223;237 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The observed inhibition was in agreement with the association of G48V and I50V with clinical resistance to SQV and DRV, respectively. 2008 Journal of molecular biology Abstract HIV G48V;I50V 65;74 69;78 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The PR contacts with DRV were closer in PR(G48V)-DRV than in the wild-type PR-DRV, whereas they were longer in PR(I54M)-DRV. 2008 Journal of molecular biology Abstract HIV G48V;I54M 37;108 55;124 PR;PR;PR;PR 4;40;75;111 6;42;77;113 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The relative inhibition of PR(I54V) and that of PR(I54M) were similar for SQV and DRV. 2008 Journal of molecular biology Abstract HIV I54M;I54V 48;27 56;35 PR;PR 27;48 29;50 18600296 False I50V resistance readings of HIV isolates: co-amplification of NASBA HIV-1 RNA QT internal calibrators and HIV-1 patient isolates may lead to a false I50V mutation resistance reading in genotypic tests. Q calibrators showed the PI resistance mutation I50V when directly amplified and sequenced from the 423-bp PCR product targeting protease gene. 2008 Archives of virology Abstract HIV I50V 48 52 PR;PI 129;25 137;27 18600296 False I50V resistance readings of HIV isolates: co-amplification of NASBA HIV-1 RNA QT internal calibrators and HIV-1 patient isolates may lead to a false I50V mutation resistance reading in genotypic tests. The I50V protease inhibitor (PI) resistance mutation was found in 87.4% of protease gene fragments sequenced from 199 nucleic acid isolates extracted using an NASBA virus load assay, performed between 1997 and 2001 in Brazil. 2008 Archives of virology Abstract HIV I50V 4 8 PR;PR;PI 9;75;29 17;83;31 18600296 False I50V resistance readings of HIV isolates: co-amplification of NASBA HIV-1 RNA QT internal calibrators and HIV-1 patient isolates may lead to a false I50V mutation resistance reading in genotypic tests. The majority of the patients' samples had a mixture of I50I and I50V; however, this artifact was nor seen when a 989-bp PCR product was used. 2008 Archives of virology Abstract HIV I50I;I50V 55;64 59;68 18603011 Identification of amino acid residues in HIV-1 Vif critical for binding and exclusion of APOBEC3G/F. Another unique mutant designated Y69A incompetent against both of A3G/F was also identified. 2008 Microbes and infection Abstract HIV Y69A 33 37 18603011 Identification of amino acid residues in HIV-1 Vif critical for binding and exclusion of APOBEC3G/F. By single-cycle replication and immunoprecipitation/immunoblotting analyses, mutants designated W21A, S32A, W38A, Y40A, and H43A were demonstrated to hardly or poorly bind to and neutralize A3G. 2008 Microbes and infection Abstract HIV H43A;S32A;W21A;W38A;Y40A 124;102;96;108;114 128;106;100;112;118 18603011 Identification of amino acid residues in HIV-1 Vif critical for binding and exclusion of APOBEC3G/F. Interestingly, while mutants designated E76A and W79A acted normally to inactivate A3G, they were found to exhibit a Vif-defective phenotype against A3F. 2008 Microbes and infection Abstract HIV E76A;W79A 40;49 44;53 Vif 117 120 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. CONCLUSION: Defects generated at the level of core assembly and stability by S149A and S178A mutations are sensitive to the way of delivery of viral nucleoprotein complexes into the target cell. 2008 Retrovirology Abstract HIV S149A;S178A 77;87 82;92 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Morphological analysis of viral particles and in vitro uncoating assays of isolated cores demonstrated that infectivity defects resulted from disruption of the viral core assembly and stability for S149A and S178A mutants, respectively. 2008 Retrovirology Abstract HIV S149A;S178A 198;208 203;213 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. RESULTS: Here, we show that infectivity of HIV-1 mutants bearing S149A and S178A mutations in CA can be efficiently restored when pseudotyped with vesicular stomatitis virus envelope glycoprotein, that addresses the mutant cores through the endocytic pathway rather than by fusion at the plasma membrane. 2008 Retrovirology Abstract HIV S149A;S178A 65;75 70;80 Capsid;Env 94;174 96;182 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. S149A and S178A mutants were unable to complete reverse transcription and/or produce 2-LTR DNA. 2008 Retrovirology Abstract HIV S178A;S149A 10;0 15;5 LTR;RT 87;48 90;69 18614259 Anti-HIV evaluation of benzo[d]isothiazole hydrazones. Target compounds tested in MT-4 cells cultures for their anti-HIV properties against wild type HIV-1 and HIV strains carrying clinically relevant mutations (EFV(R), Y181C and K103/Y181C) showed good activity against wild type HIV-1 and against the EFV(R) mutant. 2009 European journal of medicinal chemistry Abstract HIV Y181C;Y181C 180;165 185;170 18614864 Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. 2008 AIDS (London, England) Abstract HIV K103N;L90M;M184V 83;128;93 88;132;98 RT;PR 102;136 123;144 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. BACKGROUND: The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase can be selected by abacavir, didanosine, tenofovir, and stavudine in vivo resulting in reduced susceptibility to these drugs and decreased viral replication capacity. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 16 20 RT 69 90 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. CONCLUSIONS: A62V and S68G serve as partial compensatory mutations for the K65R mutation in reverse transcriptase by improving the viral replication capacity, which is likely due to increased incorporation efficiency of the natural substrates. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V;K65R;S68G 13;75;22 17;79;26 RT 92 113 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. In clinical isolates, K65R is frequently accompanied by the A62V and S68G reverse transcriptase mutations. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V;K65R;S68G 60;22;69 64;26;73 RT 74 95 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. METHODS: The role of A62V and S68G in combination with K65R was investigated using phenotypic, viral growth competition, pre-steady-state kinetic, and excision analyses. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V;K65R;S68G 21;55;30 25;59;34 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. Pre-steady-state kinetic analysis demonstrated that K65R resulted in a decreased rate of incorporation (kpol) for all natural dNTPs, which were partially restored to wild-type levels by addition of A62V and S68G. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V;K65R;S68G 198;52;207 202;56;211 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. RESULTS: Addition of A62V and S68G to K65R caused no significant change in human immunodeficiency virus type 1 resistance to abacavir, didanosine, tenofovir, or stavudine but partially restored the replication defect of virus containing K65R. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V;K65R;K65R;S68G 21;38;237;30 25;42;241;34 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. The triple mutant K65R+A62V+S68G still showed some replication defect compared with wild-type virus. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V;K65R;S68G 23;18;28 27;22;32 18614922 The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation. When added to K65R and S68G, the A62V mutation seemed to restore adenosine triphosphate-mediated excision of tenofovir to wild-type levels. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A62V;K65R;S68G 33;14;23 37;18;27 18615118 HIV-1 drug resistance mutations: an updated framework for the second decade of HAART. More than 50 reverse transcriptase mutations are associated with nucleoside reverse transcriptase inhibitor resistance including M184V, thymidine analog mutations, mutations associated with non-thymidine analog containing regimens, multi-nucleoside resistance mutations, and several recently identified accessory mutations. 2008 AIDS reviews Abstract HIV M184V 129 134 NRTI;RT 65;13 97;34 18620490 Short communication: high prevalence of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients in Greenland. The most prevalent mutations were T69D/N (15%), K70R (15%), and M184V (10%). 2008 AIDS research and human retroviruses Abstract HIV K70R;M184V;T69D;T69N 48;64;34;34 52;69;40;40 18620491 Analysis of near full-length genomic sequences of drug-resistant HIV-1 spreading among therapy-naive individuals in Nagoya, Japan: amino acid mutations associated with viral replication activity. All 12 viruses conserved both an H87Q mutation in the cyclophilin A-binding site of Gag p24 (capsid) and a T23N mutation in the cysteine-rich domain of Tat protein. 2008 AIDS research and human retroviruses Abstract HIV H87Q;T23N 33;107 37;111 Capsid;p24;Tat;Gag 93;88;152;84 99;91;155;87 18620491 Analysis of near full-length genomic sequences of drug-resistant HIV-1 spreading among therapy-naive individuals in Nagoya, Japan: amino acid mutations associated with viral replication activity. Genomes comprised seven protease inhibitor (PI)-resistant viruses possessing an M46I (n = 6) or L90M mutation (n = 1) and five non-nucleoside reverse transcriptase inhibitor-resistant viruses possessing a K103N mutation. 2008 AIDS research and human retroviruses Abstract HIV K103N;L90M;M46I 205;96;80 210;100;84 NNRTI;PR;PI 127;24;44 163;32;46 18620491 Analysis of near full-length genomic sequences of drug-resistant HIV-1 spreading among therapy-naive individuals in Nagoya, Japan: amino acid mutations associated with viral replication activity. PI-resistant viruses commonly possessed two cleavage site mutations in the p6(Pol)/protease of Pol polyprotein (F48L in p6(Pol)) and the anchor/core domains of Nef protein (L57V). 2008 AIDS research and human retroviruses Abstract HIV F48L;L57V 112;173 117;177 PR;Pol;Pol;Pol;Nef;Gag;Gag;PI 83;78;95;123;160;75;120;0 91;81;98;126;163;77;122;2 18622680 HIV-2 amino acid substitutions in Gag and Env proteins occurring simultaneously with viral load upsurge in a drug-naive patient. Only one amino acid substitution (V286I) was observed with an increase in HIV-2 load in the Gag region where the clustering of epitopes was reported. 2008 Journal of infection and chemotherapy Abstract HIV V286I 34 39 Gag 92 95 18622680 HIV-2 amino acid substitutions in Gag and Env proteins occurring simultaneously with viral load upsurge in a drug-naive patient. Three amino acid substitutions (V2861 in Gag, K303T and N337 K/R in Env) were observed from months 29 to 40. 2008 Journal of infection and chemotherapy Abstract HIV K303T;N337K;N337R 46;56;56 51;64;64 Env;Gag 68;41 71;44 18625269 Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Q148R and F121Y were the two main pathways of resistance to S/GSK-364735. 2008 Antiviral research Abstract HIV F121Y;Q148R 10;0 15;5 18625269 Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Q148R/K and N155H, which were found in patients failing raltegravir treatment in Phase IIb studies, were observed during passage with raltegravir with this method. 2008 Antiviral research Abstract HIV N155H;Q148K;Q148R 12;0;0 17;7;7 18625773 Tipranavir-ritonavir genotypic resistance score in protease inhibitor-experienced patients. Mutations at six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E, Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was associated with a higher VR (F53L/W/Y). 2008 Antimicrobial agents and chemotherapy Abstract HIV E35D;E35G;E35K;E35N;F53L;F53W;F53Y;H69I;H69K;H69N;H69Q;H69R;H69Y;L89I;L89M;L89R;L89T;L89V;M36I;M36L;M36V;Q58E;Q61D;Q61E;Q61G;Q61H;Q61N;Q61R 59;59;59;59;188;188;188;103;103;103;103;103;103;123;123;123;123;123;71;71;71;81;87;87;87;87;87;87 69;69;69;69;196;196;196;117;117;117;117;117;117;135;135;135;135;135;79;79;79;85;101;101;101;101;101;101 18625773 Tipranavir-ritonavir genotypic resistance score in protease inhibitor-experienced patients. The genotypic score M36I/L/V-53L/W/Y + Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong association with VR. 2008 Antimicrobial agents and chemotherapy Abstract HIV M36I;M36L;M36V;H69I;H69K;H69N;H69Q;H69R;H69Y;L89I;L89M;L89R;L89T;L89V;Q58E 20;20;20;46;46;46;46;46;46;63;63;63;63;63;39 28;28;28;60;60;60;60;60;60;75;75;75;75;75;43 18629940 Site-directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16. D176N and E274Q CXCR6 mutants were unable to interact with soluble CXCL16, suggesting a critical role for D176 and E274 in ligand binding. 2008 European journal of immunology Abstract HIV E274Q;D176N 10;0 15;5 18629940 Site-directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16. Intriguingly, although unable to interact with soluble CXCL16, the E274Q mutant could promote robust adhesion to membrane-anchored CXCL16, suggesting that soluble and membrane-bound forms of CXCL16 possess distinct conformations. 2008 European journal of immunology Abstract HIV E274Q 67 72 18630898 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profile. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L100I mutated RTs) assays, compounds carrying an ethyl/ iso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. 2008 Journal of medicinal chemistry Abstract HIV K103N;K103N;L100I;Y181C;Y181I;Y188L 43;97;115;50;104;61 48;102;120;55;109;66 RT 129 132 18630898 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profile. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs. 2008 Journal of medicinal chemistry Abstract HIV Y181C 170 175 RT 176 179 18632295 Nucleoside reverse transcriptase inhibitor resistance mutations in subtype F1 strains isolated from heavily treated adolescents in Romania. Although the combination of K65R mutation with TAMs has rarely been reported because of their antagonistic effects on NRTI resistance, its presence was confirmed by clonal analysis of one strain. 2009 International journal of infectious diseases Abstract HIV K65R 28 32 NRTI 118 122 18632295 Nucleoside reverse transcriptase inhibitor resistance mutations in subtype F1 strains isolated from heavily treated adolescents in Romania. The RT gene carrying the K65R mutation and thymidine analog mutations (TAMs) was cloned into pGEM-T vector (Promega), followed by sequencing. 2009 International journal of infectious diseases Abstract HIV K65R 25 29 RT 4 6 18633939 The application of perfluorooctanoate to investigate trimerization of the human immunodeficiency virus-1 gp41 ectodomain by electrophoresis. In addition, the proteins expressed from the two mutants in the heptad repeat (HR) domains of gp41, I62P, and N126K, were also examined by the PFO-PAGE analysis for functional ramification of molecular organization. 2008 Electrophoresis Abstract HIV I62P;N126K 100;110 104;115 gp41 94 98 18633939 The application of perfluorooctanoate to investigate trimerization of the human immunodeficiency virus-1 gp41 ectodomain by electrophoresis. Remarkably, the I62P mutation completely abolished the gp41 trimer formation, whereas the N126K mutation resulted in a more stable trimer. 2008 Electrophoresis Abstract HIV I62P;N126K 16;90 20;95 gp41 55 59 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. RESULTS: The V38A mutant made up >or=85% of the quasispecies at baseline and decayed to <5% over 12-24 weeks; plasma HIV-1 RNA levels remained stable during this time. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V38A 13 17 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Subsequently, ENF was readministered for 4 weeks as "pulse intensification." METHODS: The proportion of plasma virus carrying the V38A mutation in gp41 was quantified by allele-specific real-time polymerase chain reaction in serial samples collected from 3 subjects at 1- to 4-week intervals. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V38A 130 134 Pol;gp41 196;147 206;151 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The relative stability of plasma HIV-1 titers during decay of V38A suggests that factors other than viral fitness likely define viral load set-point in patients with advanced disease. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V38A 62 66 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The V38A mutant virus reemerged rapidly during the ENF pulse. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V38A 4 8 18646335 Prevalence of drug resistance and associated mutations in HIV-positive Puerto Ricans: sex variations. The most prevalent mutations in the protease gene were L63P, M361, L90M, A71V, and L101. 2008 Ethnicity & disease Abstract HIV A71V;L63P;L90M 73;55;67 77;59;71 PR 36 44 18646335 Prevalence of drug resistance and associated mutations in HIV-positive Puerto Ricans: sex variations. The most prevalent mutations in the reverse transcriptase gene were M184V, K103N, T215Y, and M41L. 2008 Ethnicity & disease Abstract HIV K103N;M184V;M41L;T215Y 75;68;93;82 80;73;97;87 RT 36 57 18651855 Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy. A gradual accumulation of new mutations was observed in all patients, including G140S, Q148H and N155H in patient 1, L74I in patient 2, and G140S in patient 3. 2008 HIV medicine Abstract HIV G140S;G140S;L74I;N155H;Q148H 80;140;117;97;87 85;145;121;102;92 18651855 Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy. Clonal analysis showed the coexistence, in patient 1, of the two common resistance pathways (mutations Q148R/H and N155H) found in distinct quasi-species. 2008 HIV medicine Abstract HIV N155H;Q148H;Q148R 115;103;103 120;110;110 18651855 Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy. RESULTS: At the time of VF, RAL-resistance mutations were selected: (i) Q148R in patients 1 and 3; (ii) T66A and E92Q in patient 2. 2008 HIV medicine Abstract HIV E92Q;Q148R;T66A 113;70;102 117;77;108 18662109 Etravirine for the treatment of HIV infection. This conformation confers an increased genetic barrier to resistance compared with other NNRTIs: multiple mutations are required before there is a decrease in susceptibility to etravirine; whereas, only one mutation (K103N) is typically needed to confer high-level resistance to the first-generation NNRTIs. 2008 Expert review of anti-infective therapy Abstract HIV K103N 217 222 NNRTI;NNRTI 89;300 95;306 18662137 Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. For the K65R mutation in the HIV reverse transcriptase (multinucleoside resistance), incidences were 5.3% (95% CI, 2.4%-9.9%) and 0.0% (95% CI, 0.0%-3.6%; P= .01), respectively, in patients treated with non-zidovudine-containing regimens. 2008 Clinical infectious diseases Abstract HIV K65R 8 12 RT 33 54 18662137 Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Of failures that were successfully genotyped, the M184V mutation in the HIV reverse transcriptase (lamivudine resistance) occurred in 35.3% (95% CI, 29.3%-41.6%) of patients who started NNRTI-based HAART, compared with 21.0% (95% CI, 14.4%-28.8%; P< .001) for those who received a bPI. 2008 Clinical infectious diseases Abstract HIV M184V 50 55 RT;NNRTI 76;186 97;191 18662701 Mechanistic basis of zidovudine hypersusceptibility and lamivudine resistance conferred by the deletion of codon 69 in the HIV-1 reverse transcriptase coding region. Common mutational patterns involve the deletion of Asp67 (Delta 67) and mutations such as K70R and T215F or T215Y, or the deletion of Thr69 (Delta 69) and mutations of the Q151M complex. 2008 Journal of molecular biology Abstract HIV K70R;Q151M;T215F;T215Y 90;172;99;108 94;177;104;113 Asp 51 54 18662701 Mechanistic basis of zidovudine hypersusceptibility and lamivudine resistance conferred by the deletion of codon 69 in the HIV-1 reverse transcriptase coding region. Human immunodeficiency virus type 1 clones containing Delta 69 in a multidrug-resistant sequence background, including the Q151M complex and substitutions K103N, Y181C, M184V, and G190A, showed high-level resistance to all tested nucleoside RT inhibitors. 2008 Journal of molecular biology Abstract HIV G190A;K103N;M184V;Q151M;Y181C 180;155;169;123;162 185;160;174;128;167 RT 241 243 18665583 Structural basis for the improved drug resistance profile of new generation benzophenone non-nucleoside HIV-1 reverse transcriptase inhibitors. Structures of mutant RTs (K103N, V106A/Y181C) with benzophenones showed only small rearrangements of the NNRTIs relative to wild-type. 2008 Journal of medicinal chemistry Abstract HIV K103N;V106A;Y181C 26;33;39 31;38;44 NNRTI;RT 105;21 111;24 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. Eight validated real-time PCR-based assays were used to test for minority drug resistance mutations (protease L90M and reverse transcriptase M41L, K70R, K103N, Y181C, M184V, and T215F/Y) above naturally occurring frequencies. 2008 PLoS medicine Abstract HIV K103N;K70R;L90M;M184V;M41L;T215F;T215Y;Y181C 153;147;110;167;141;178;178;160 158;151;114;172;145;185;185;165 PR;RT 101;119 109;140 18667707 HIV-1 reverse transcriptase connection subdomain mutations reduce template RNA degradation and enhance AZT excision. To test the predictions of this model, we analyzed the effects of previously identified cn mutations in combination with thymidine analog mutations (D67N, K70R, T215Y, and K219Q) on in vitro RNase H activity and AZT monophosphate (AZTMP) excision. 2008 Proc Natl Acad Sci U S A Abstract HIV D67N;K219Q;K70R;T215Y 149;172;155;161 153;177;159;166 18667707 HIV-1 reverse transcriptase connection subdomain mutations reduce template RNA degradation and enhance AZT excision. We found that cn mutations G335C/D, N348I, A360I/V, V365I, and A376S decreased primary and secondary RNase H cleavages. 2008 Proc Natl Acad Sci U S A Abstract HIV A360I;A360V;A376S;G335C;G335D;N348I;V365I 43;43;63;27;27;36;52 50;50;68;34;34;41;57 18667925 HIV drug resistance pattern among HAART-exposed patients with suboptimal virological response in Ouagadougou, Burkina Faso. Although not significant, other TAMs (M41L, T215F/Y, K219Q/E) also occurred more frequently among CRF06_cpx strains as well. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K219E;K219Q;M41L;T215F;T215Y 53;53;38;44;44 60;60;42;51;51 18667925 HIV drug resistance pattern among HAART-exposed patients with suboptimal virological response in Ouagadougou, Burkina Faso. Dominant mutations included M46I (37%), 154V (26%), V82A/T/F (30%) in PR; K103N (44%), G190A/S (16%) and T215F/Y (48%) (NRTIs) in RT. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G190A;G190S;K103N;M46I;T215F;T215Y;V82A;V82F;V82T 87;87;74;28;105;105;52;52;52 94;94;79;32;112;112;60;60;60 NRTI;PR;RT 120;70;130 125;72;132 18667925 HIV drug resistance pattern among HAART-exposed patients with suboptimal virological response in Ouagadougou, Burkina Faso. Some resistance mutations, notably D67N/G, K70R and L210W (thymidine analogue mutations-TAMs); K101E, V179E in RT, 154V, V82A/T/F and L90M in PR were significantly higher among CRF06_cpx than CRF02_AG strains (P < 0.05). 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D67G;D67N;K101E;K70R;L210W;L90M;V179E;V82A;V82F;V82T 35;35;95;43;52;134;102;121;121;121 41;41;100;47;57;138;107;129;129;129 PR;RT 142;111 144;113 18667928 Phylogenetic investigation of transmission pathways of drug-resistant HIV-1 utilizing pol sequences derived from resistance genotyping. Several discrete clusters involving transmission of K103N- and/or M41L-resistant virus to multiple recipients were detected, suggesting that multiple transmission pathways can exist for viruses with the same resistance mutations. 2008 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;M41L 52;66 57;70 18672539 Prevalence and risk factors for etravirine resistance among patients failing on non-nucleoside reverse transcriptase inhibitors. The most frequent mutations were G190A (230%), Y181C (23%) and K101E (14.1%). 2008 Antiviral therapy Abstract HIV G190A;K101E;Y181C 33;63;47 38;68;52 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. METHODS: We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A). 2008 The Journal of infectious diseases Abstract HIV G190A;K103N;Y181C 221;203;210 226;208;215 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. All primary INI-resistance mutations with the exception of E157Q--which was present in 1.1% of sequences--were nonpolymorphic. 2008 Retrovirology Abstract HIV E157Q 59 71 IN 12 15 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Several accessory INI-resistance mutations including L74M, T97A, V151I, G163R, and S230N were also polymorphic with polymorphism rates ranging between 0.5% to 2.0%. 2008 Retrovirology Abstract HIV G163R;L74M;S230N;T97A;V151I 72;53;83;59;65 77;57;88;63;70 IN 18 21 18690163 Pattern and impact of emerging resistance mutations in treatment experienced patients failing darunavir-containing regimen. Emergence of DRV-associated-resistance mutations was observed in 72% (18/25) of patients, at codons L89I/M/V (32%), V32I (28%), V11I (20%), I47V/A (20%), I54L/M (20%), L33F/I (16%) and I50V (16%). 2008 AIDS (London, England) Abstract HIV I47A;I47V;I50V;I54L;I54M;L33F;L33I;L89I;L89M;L89V;V11I;V32I 140;140;185;154;154;168;168;100;100;100;128;116 146;146;189;160;160;174;174;108;108;108;132;120 18692068 Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease. Although the Ile50Val mutation leads to a significant decrease in affinity for all compounds in this series, they retain or even show increased affinity towards the important Ile84Val mutation. 2008 Journal of molecular biology Abstract HIV I50V;I84V 13;175 21;183 18692068 Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease. Herein, we report the influence of the active-site mutations Ile50Val and Ile84Val on these inhibitors by structural and kinetic analysis. 2008 Journal of molecular biology Abstract HIV I50V;I84V 61;74 69;82 18701346 Tipranavir resistance associated mutations in protease inhibitor-naive patients with HIV-1 subtype A/E infection. Patients with subtype A/E had higher prevalence of I13V (54% vs. 21%, P=0.011), M36I (96% vs. 53%, P<0.001), H69K (68% vs. 26%, P=0.001), and >2 TPV-RAMs (62% vs. 21%, P=0.002). 2008 Journal of clinical virology Abstract HIV M36I;H69K;I13V 80;109;51 84;113;55 18701346 Tipranavir resistance associated mutations in protease inhibitor-naive patients with HIV-1 subtype A/E infection. The most common TPV-RAMs were M36I (88%), H69K (61%), and I13V (48%). 2008 Journal of clinical virology Abstract HIV H69K;I13V;M36I 42;58;30 46;62;34 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Q148K and T66I conferred the highest resistance to both drugs while S153Y conferred relatively greater resistance to elvitegravir than raltegravir. 2008 Biochemistry Abstract HIV S153Y;T66I;Q148K 68;10;0 73;14;5 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Q148K was also markedly impaired for 3'-P. 2008 Biochemistry Abstract HIV Q148K 0 5 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The aims of the present study were (1) to investigate and compare the effects of raltegravir and elvitegravir on the three IN-mediated reactions, 3'-processing (3'-P), strand transfer (ST), and disintegration, (2) to determine the biochemical activities of seven IN mutants (T66I, L74M, E92Q, F121Y, Q148K, S153Y, and N155H) previously selected from drug-resistant patients and isolates, and (3) to determine the resistance profile for raltegravir and elvitegravir in those IN mutants. 2008 Biochemistry Abstract HIV E92Q;F121Y;L74M;N155H;Q148K;S153Y;T66I 287;293;281;318;300;307;275 291;298;285;323;305;312;279 IN;IN;IN 123;263;474 125;265;476 18715920 Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. In addition, mutations that do not confer reduced susceptibility when present alone (H114Y, L74M, R20K, A128T, E138K, and S230R) are also discussed in relation to their position in the catalytic core domain and their proximity to known structural features of integrase. 2008 Journal of virology Abstract HIV A128T;E138K;H114Y;L74M;R20K;S230R 104;111;85;92;98;122 109;116;90;96;102;127 IN 259 268 18715920 Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. We find the primary resistance-conferring mutations to be Q148R, E92Q, and T66I and demonstrate that they confer a reduction in susceptibility not only to elvitegravir but also to raltegravir (MK-0518) and other integrase inhibitors. 2008 Journal of virology Abstract HIV E92Q;Q148R;T66I 65;58;75 69;63;79 IN 212 221 18715933 Minority human immunodeficiency virus type 1 variants in antiretroviral-naive persons with reverse transcriptase codon 215 revertant mutations. T215 revertant mutations such as T215C/D/E/S that evolve from the nucleoside reverse transcriptase (RT) inhibitor mutations T215Y/F have been found in about 3% of human immunodeficiency virus type 1 (HIV-1) isolates from newly diagnosed HIV-1-infected persons. 2008 Journal of virology Abstract HIV T215C;T215D;T215E;T215F;T215S;T215Y 33;33;33;124;33;124 44;44;44;131;44;131 NRTI;RT 66;100 98;102 HIV infections 237 251 18715933 Minority human immunodeficiency virus type 1 variants in antiretroviral-naive persons with reverse transcriptase codon 215 revertant mutations. T215Y or T215F was not detected in any of the revertant or control samples; however, 4 of 22 revertant samples had one or more T215 revertants that were detected by UDPS but not by direct PCR sequencing. 2008 Journal of virology Abstract HIV T215F;T215Y 9;0 14;5 18715933 Minority human immunodeficiency virus type 1 variants in antiretroviral-naive persons with reverse transcriptase codon 215 revertant mutations. The failure to detect viruses with T215Y/F in the 22 revertant samples in this study may result from the overwhelming replacement of transmitted T215Y variants by the more fit T215 revertants or from the primary transmission of a T215 revertant in a subset of persons with T215 revertants. 2008 Journal of virology Abstract HIV T215F;T215Y;T215Y 35;35;145 42;42;150 18715933 Minority human immunodeficiency virus type 1 variants in antiretroviral-naive persons with reverse transcriptase codon 215 revertant mutations. We used a newly developed sequencing method-ultradeep pyrosequencing (UDPS; 454 Life Sciences)--to determine the frequency with which T215Y/F or other RT inhibitor resistance mutations could be detected as minority variants in samples from untreated persons that contain T215 revertants ("revertant" samples) compared with samples from untreated persons that lack such revertants ("control" samples). 2008 Journal of virology Abstract HIV T215F;T215Y 134;134 141;141 RT 151 153 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. In addition to a characteristic increase in charge in the V3 loop homologue of FIVFL4, we identified two mutations in potential sites for N-linked glycosylation in the region of FIV Env analogous to the V1-V2 region of HIV and SIV Env, T271I and N342Y. 2008 Retrovirology Abstract HIV N342Y;T271I 246;236 251;241 Env;Env 182;231 185;234 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The T271I mutation did not confer CD134-independent infection upon GL8 or CPG41, nor did it increase the affinity of the CXCR4 interaction, suggesting that the principal effect was targeted at reducing the complexity of the Env-CD134 interaction. 2008 Retrovirology Abstract HIV T271I 4 9 Env 224 227 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. When these mutations were introduced into the primary GL8 and CPG41 strains of FIV, the T271I mutation was found to alter the nature of the virus-CD134 interaction; primary viruses carrying the T271I mutation no longer required determinants in cysteine-rich domain (CRD) 2 of CD134 for viral entry. 2008 Retrovirology Abstract HIV T271I;T271I 88;194 93;199 18723511 Avian sarcoma virus and human immunodeficiency virus, type 1 use different subsets of ESCRT proteins to facilitate the budding process. In contrast to ASV Gag, HIV-1 Gag containing an L domain inactivating mutation (P7L) was efficiently rescued by fusion to a component of ESCRT-III (Chmp6) but not ESCRT-II (Eap20). 2008 The Journal of biological chemistry Abstract HIV P7L 80 83 Gag;Gag 19;30 22;33 18728003 Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors". Binding studies revealed that the M184V change reduces the affinity to INDOPY-1, while Y115F facilitates binding of the natural nucleotide substrate and the combined effects enhance the ability of the enzyme to discriminate against the inhibitor. 2008 The Journal of biological chemistry Abstract HIV M184V;Y115F 34;87 39;92 18728003 Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors". K65R can partially counteract these effects. 2008 The Journal of biological chemistry Abstract HIV K65R 0 4 18728003 Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors". K65R, susceptibility to INDOPY-1. 2008 The Journal of biological chemistry Abstract HIV K65R 0 4 18728003 Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors". M184V and Y115F, or increased. 2008 The Journal of biological chemistry Abstract HIV Y115F;M184V 10;0 15;5 18728003 Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against "nucleotide-competing reverse transcriptase inhibitors". RT enzymes containing the isolated mutations M184V and Y115F cause 2-3-fold increases in IC(50) values, while the combination of the two mutations causes a >15-fold increase. 2008 The Journal of biological chemistry Abstract HIV M184V;Y115F 45;55 50;60 RT 0 2 18729771 Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV type 1 subtype G and CRF02_AG. In addition, there was an inverse association between P5L/T mutations in p6 and thymidine analog mutations in reverse transcriptase (p = 0.0001), and drug nonadherence was associated with an 8-fold lower risk of having a nonsubstitutionary mutation in p6 (95% CI = 1.27-52.57). 2008 AIDS research and human retroviruses Abstract HIV P5L;P5T 54;54 59;59 RT;Gag;Gag 110;73;252 131;75;254 18729771 Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV type 1 subtype G and CRF02_AG. The data also suggested that P5L/T may be a compensatory mutation for the loss of an essential phosphorylation site in p6. 2008 AIDS research and human retroviruses Abstract HIV P5L;P5T 29;29 34;34 Gag 119 121 18729771 Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV type 1 subtype G and CRF02_AG. The P5L/T mutation was inversely correlated with the presence of K27Q/N in p6, with each mutation being more prominent in subtype G and CRF02_AG, respectively. 2008 AIDS research and human retroviruses Abstract HIV K27N;K27Q;P5L;P5T 65;65;4;4 71;71;9;9 Gag 75 77 18753116 Evaluation of efficacy, safety, pharmacokinetics, and adherence in HIV-1-infected, antiretroviral-naive patients treated with ritonavir-boosted atazanavir plus fixed-dose tenofovir DF/emtricitabine given once daily. No K65R or ATV/r associated mutations emerged; M184V developed in one patient. 2008 HIV clinical trials Abstract HIV K65R;M184V 3;47 7;52 18753927 Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility. Control Q148R mutant virus showed fold change values of 17.85 +/- 2.77 and 88.94 +/- 9.02 for raltegravir and elvitegravir, respectively, whereas the average fold change for the clinical samples was 0.91 +/- 0.40, and 0.84 +/- 0.37. 2008 AIDS (London, England) Abstract HIV Q148R 8 13 18762167 Deletion of fusion peptide or destabilization of fusion core of HIV gp41 enhances antigenicity and immunogenicity of 4E10 epitope. Here we used pIg-tail expression system to construct a panel of eukaryotic cell-surface expression plasmids encoding the extracellular domain of gp41 with deletion of fusion peptide and/or introduction of L568P mutation that may disrupt the gp41 six-helix bundle core conformation as DNA vaccines for immunization of mice. 2008 Biochemical and biophysical research communications Abstract HIV L568P 205 210 gp41;gp41 145;241 149;245 18765410 Impact of gag mutations on selection of darunavir resistance mutations in HIV-1 protease. CONCLUSIONS: In these PI-treated patients experiencing treatment failure of a darunavir-containing regimen, we showed that mutations in the gag region NC-p1/TFP-p6/p6pol may influence the selection of darunavir resistance mutations; in particular, the I437T/V gag mutation that confers resistance to PIs reduces the selection of such mutations. 2008 The Journal of antimicrobial chemotherapy Abstract HIV I437T;I437V 252;252 259;259 Gag;Gag;NC;Gag;PI;PI 140;260;151;161;22;300 143;263;153;163;24;303 18765410 Impact of gag mutations on selection of darunavir resistance mutations in HIV-1 protease. The I437T/V mutation in gag and the L76V mutation in the protease were associated with a lower risk of selecting darunavir resistance mutations. 2008 The Journal of antimicrobial chemotherapy Abstract HIV I437T;I437V;L76V 4;4;36 11;11;40 PR;Gag 57;24 65;27 18765410 Impact of gag mutations on selection of darunavir resistance mutations in HIV-1 protease. There was an association between the presence of the mutation A431V in the gag sequence and the selection of the L76V mutation in the protease sequence in the latest available rebound. 2008 The Journal of antimicrobial chemotherapy Abstract HIV A431V;L76V 62;113 67;117 PR;Gag 134;75 142;78 18765410 Impact of gag mutations on selection of darunavir resistance mutations in HIV-1 protease. Virus with L76V in protease or I437T/V in gag may be already resistant to darunavir and, therefore, no additional resistance mutations need to be selected. 2008 The Journal of antimicrobial chemotherapy Abstract HIV I437T;I437V;L76V 31;31;11 38;38;15 PR;Gag 19;42 27;45 18768960 Active-site mutations in the South african human immunodeficiency virus type 1 subtype C protease have a significant impact on clinical inhibitor binding: kinetic and thermodynamic study. Study of active-site mutations (the V82A single mutation and the V82F I84V double mutation) in the less-studied South African HIV type 1 subtype C (C-SA) protease indicated that neither mutation had a significant impact on the proteolytic functioning of the protease. 2008 Journal of virology Abstract HIV I84V;V82A;V82F 70;36;65 74;40;69 PR;PR 154;258 162;266 18768960 Active-site mutations in the South african human immunodeficiency virus type 1 subtype C protease have a significant impact on clinical inhibitor binding: kinetic and thermodynamic study. Therefore, our results show that the C-SA V82F I84V double mutation decreased the binding affinities of protease inhibitors to levels significantly lower than that required for effective inhibition. 2008 Journal of virology Abstract HIV I84V;V82F 47;42 51;46 PR 104 112 18768964 Conserved salt bridge between the N- and C-terminal heptad repeat regions of the human immunodeficiency virus type 1 gp41 core structure is critical for virus entry and inhibition. We show that Asp(632) substitutions with positively charged residues (D632K and D632R) or a hydrophobic residue (D632V) could completely abolish Env-mediated viral entry, while a protein with a conserved substitution (D632E) retained its activity. 2008 Journal of virology Abstract HIV D632E;D632K;D632R;D632V 218;70;80;113 223;76;85;118 Asp;Env 13;145 16;148 18771059 Effect of tenofovir subtraction on HIV plasma viraemia, CD4+ T-cell count and resistance in a patient with baseline K65R and M184V mutations. Although limited by the single-case nature, the data support a hypothesis that there is no HIV viral RNA or CD4+ T-cell count benefit of taking tenofovir for experienced patients with genotypic evidence of K65R/M184V. 2008 Antiviral therapy Abstract HIV K65R;M184V 206;211 210;216 18771059 Effect of tenofovir subtraction on HIV plasma viraemia, CD4+ T-cell count and resistance in a patient with baseline K65R and M184V mutations. Here, we assessed the effect of tenofovir discontinuation for a patient receiving antiretroviral therapy whose HIV-1 had a dominant K65R/M184V genotype. 2008 Antiviral therapy Abstract HIV K65R;M184V 132;137 136;142 18771059 Effect of tenofovir subtraction on HIV plasma viraemia, CD4+ T-cell count and resistance in a patient with baseline K65R and M184V mutations. In vitro, the reverse transcriptase mutation K65R can simultaneously reduce drug susceptibility, replicative capacity and restrict HIV-1 replication. 2008 Antiviral therapy Abstract HIV K65R 45 49 RT 14 35 18772135 Residues in the HIV-1 capsid assembly inhibitor binding site are essential for maintaining the assembly-competent quaternary structure of the capsid protein. CA variants carrying mutations Y169A, L211A, or L211S had a reduced affinity for CAI and were unable to form mature-like particles in vitro. 2008 The Journal of biological chemistry Abstract HIV L211A;L211S;Y169A 38;48;31 43;53;36 Capsid 0 2 18786939 Detection of low-frequency K103N mutants after unstructured discontinuation of efavirenz in the presence of the CYP2B6 516 TT polymorphism. Population sequencing showed wild-type subtype D virus, whereas clonal sequencing detected low-frequency (2%) K103N. 2008 The Journal of antimicrobial chemotherapy Abstract HIV K103N 110 115 18788909 Characterization of drug-resistance mutations in HIV type 1 isolates from drug-naive and ARV-treated patients in Bulgaria. The commonest resistance mutations resulted in the NRTI mutation M184V (42.1%) and the PI mutation L90M (24.1%). 2008 AIDS research and human retroviruses Abstract HIV L90M;M184V 99;65 103;70 NRTI;PI 51;87 55;89 18799576 Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity. Consistent with a role for chromatin-associated LEDGF/p75 in stimulating integrase activity during infection, recombinant W21A protein is preferentially defective for enhancing integration into chromatinized target DNA in vitro. 2008 Journal of virology Abstract HIV W21A 122 126 IN 73 82 18799576 Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity. The A51P mutation corresponds to the S270P change in DNA methyltransferase 3B that causes human immunodeficiency, centromeric instability, and facial anomaly syndrome, revealing a critical role for this amino acid position in the chromatin binding functions of varied PWWP domains. 2008 Journal of virology Abstract HIV A51P;S270P 4;37 8;42 18806342 The impacts of current antiretroviral therapy regimens on Chinese AIDS patients and their implications for HIV-1 drug resistance mutation. The most common mutations conferring resistance to NNRTIs were K103N, Y181C and G190A, representing 56.5, 30.4 and 14.5%, respectively. 2008 Japanese journal of infectious diseases Abstract HIV G190A;K103N;Y181C 80;63;70 85;68;75 NNRTI 51 57 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. Darunavir, a potent antiviral drug, showed an unusual second binding site on the HIV-1 protease dimer surface of the V32I drug resistant mutant and normal binding in the active site cavity. 2008 Journal of medicinal chemistry Abstract HIV V32I 117 121 PR 87 95 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. The DeltaQ44 mutation has the most drastic effect since it likely disrupts the second helix. 2008 Retrovirology Abstract HIV DeltaQ44 4 12 18809675 Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. In HIV-1-infected SCID-hu Thy/Liv mice, T-20 lost activity with infrequent dosing, whereas the antiviral potency of PC-1505 was sustained, and PC-1505 was active against T-20-resistant ("DIV") virus with a G36D substitution in gp41. 2008 The Journal of biological chemistry Abstract HIV G36D 206 210 gp41 227 231 HIV infections 3 17 18815131 Role of the HIV gp120 conserved domain 1 in processing and viral entry. Based on Western blot analyses of cell lysates and virions, the entry impairment of W35A, V38A, Y39A, Y40A, G41A, V42A, and I52A is due primarily to disruption of envelope processing. 2008 The Journal of biological chemistry Abstract HIV G41A;I52A;V38A;V42A;W35A;Y39A;Y40A 108;124;90;114;84;96;102 112;128;94;118;88;100;106 Env 163 171 18815131 Role of the HIV gp120 conserved domain 1 in processing and viral entry. In contrast, the entry impairment of V44A and F53A is primarily due to disruption of the gp120-gp41 interaction, which results in dissociation of gp120 from the virion. 2008 The Journal of biological chemistry Abstract HIV F53A;V44A 46;37 50;41 gp120;gp120;gp41 89;146;95 94;151;99 18815131 Role of the HIV gp120 conserved domain 1 in processing and viral entry. The entry impairment of P43A and W45A is apparently due to a combination of effects on processing and incorporation into virions. 2008 The Journal of biological chemistry Abstract HIV P43A;W45A 24;33 28;37 18818198 The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation. The target of acyclovir in HIV-infected cells is validated as HIV reverse transcriptase (RT) by the emergence of the RT variant V75I under the selective pressure of acyclovir. 2008 The Journal of biological chemistry Abstract HIV V75I 128 132 RT;RT;RT 66;89;117 87;91;119 HIV infections 27 39 18818198 The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation. The V75I mutation is part of the multidrug resistance pathway that enhances viral resistance to many of the best RT inhibitors approved for the treatment of HIV. 2008 The Journal of biological chemistry Abstract HIV V75I 4 8 RT 113 115 18818518 HIV-1 gp41 fusogenic function triggers autophagy in uninfected cells. The gp41 fusion activity is responsible for Env-mediated autophagy since the Val2Glu mutation in the gp41 FP totally blocks this process. 2008 Autophagy Abstract HIV V2E 77 84 gp41;gp41;Env 4;101;44 8;105;47 18829756 Epigenetic silencing of human immunodeficiency virus (HIV) transcription by formation of restrictive chromatin structures at the viral long terminal repeat drives the progressive entry of HIV into latency. Silencing is greatly enhanced when the lentiviral vectors carry an attenuated Tat gene with the H13L mutation. 2008 Journal of virology Abstract HIV H13L 96 100 Tat 78 81 18829762 Cyclophilin A-dependent restriction of human immunodeficiency virus type 1 capsid mutants for infection of nondividing cells. The HIV-1 CA mutants A92E, T54A, and R132K were impaired for infection of aphidicolin-arrested HeLa cells, but not HOS cells. 2008 Journal of virology Abstract HIV A92E;R132K;T54A 21;37;27 25;42;31 Capsid 10 12 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Therefore, we introduced the N283T mutation into an env clone from a brain-derived isolate and into a brain tissue-derived env clone, and the T283N change into a spleen-derived env from the same individual; however, we found that their phenotypes were not affected. 2008 Retrovirology Abstract HIV N283T;T283N 29;142 34;147 Env;Env;Env 52;123;177 55;126;180 18838582 Drug resistance mutation profile and accumulation kinetics in human immunodeficiency virus-positive individuals infected with subtypes B and F failing highly active antiretroviral therapy are influenced by different viral codon usage patterns. Due to codon usage variation, there is a significantly lower incidence of the substitutions L210W, Q151M, and F116Y in subtype F1 isolates than in the subtype B counterparts. 2008 Antimicrobial agents and chemotherapy Abstract HIV F116Y;L210W;Q151M 110;92;99 115;97;104 18838591 Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. administration with K65R-selecting antiretroviral agents in virtual subjects using the population pharmacokinetic and cellular enzyme kinetic parameters of ZDV. 2008 Antimicrobial agents and chemotherapy Abstract HIV K65R 20 24 18838591 Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. In vitro selection studies and data from large genotype databases from clinical studies have demonstrated that tenofovir disoproxil fumarate and abacavir sulfate select for the K65R mutation in the human immunodeficiency virus type 1 polymerase region. 2008 Antimicrobial agents and chemotherapy Abstract HIV K65R 177 181 Pol 234 244 18838591 Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. is an efficacious and safe dose that could delay the emergence of the K65R mutation. 2008 Antimicrobial agents and chemotherapy Abstract HIV K65R 70 74 18838591 Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. Studies performed in vitro and in humans suggest that viruses containing the K65R mutation remained susceptible to zidovudine (ZDV) and other thymine nucleoside antiretroviral agents. 2008 Antimicrobial agents and chemotherapy Abstract HIV K65R 77 81 18838591 Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. Therefore, ZDV could be coformulated with these agents as a "resistance repellent" agent for the K65R mutation. 2008 Antimicrobial agents and chemotherapy Abstract HIV K65R 97 101 18839778 Population trends in the prevalence and patterns of protease resistance related to exposure to unboosted and boosted protease inhibitors. Individual mutations L33F, M461/L, V82A/F/T/S/L and 184V became relatively more frequent over the period of study. 2008 Antiviral therapy Abstract HIV L33F;V82A;V82F;V82L;V82S;V82T 21;35;35;35;35;35 25;47;47;47;47;47 18844463 Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility. In virus strains with the nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E and G190S, the L74V mutation increased replication capacity, consistent with published observations, but replication capacity was decreased in strains without NNRTI resistance mutations. 2008 AIDS research and human retroviruses Abstract HIV G190S;K101E;L74V 100;90;111 105;95;115 NNRTI;NNRTI;NNRTI 26;73;255 61;78;260 18844463 Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility. Introduction of M184V into several different clones expressing various RT resistance mutations uniformly decreased susceptibility to abacavir, lamivudine, and didanosine, and increased susceptibility to zidovudine, stavudine, and tenofovir; replication capacity was decreased. 2008 AIDS research and human retroviruses Abstract HIV M184V 16 21 RT 71 73 18844463 Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility. K101E and G190S together tend to decrease susceptibility to all nucleoside RT inhibitors, but the K103N mutation had little effect on nucleoside RT inhibitor susceptibility. 2008 AIDS research and human retroviruses Abstract HIV G190S;K103N;K101E 10;98;0 15;103;5 RT;RT 75;145 77;147 18844463 Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility. The L74V mutation had similar but slightly different effects, contributing to decreased susceptibility to abacavir, lamivudine, and didanosine and increased susceptibility to zidovudine and tenofovir, but in contrast to M184V, L74V contributed to decreased susceptibility to stavudine. 2008 AIDS research and human retroviruses Abstract HIV L74V;L74V;M184V 4;227;220 8;231;225 18852278 Genotypic resistance analysis of the virological response to fosamprenavir-ritonavir in protease inhibitor-experienced patients in CONTEXT and TRIAD clinical trials. The JT procedure led to selecting the CONTEXT/TRIAD genotypic set of mutations, I15V, M46I/L, I54L/M/V, D60E, L63P/T, and I84V, as providing the strongest association with the VR (P = 1.45 x 10(-11)). 2008 Antimicrobial agents and chemotherapy Abstract HIV D60E;I15V;I54L;I54M;I54V;I84V;L63P;L63T;M46I;M46L 104;80;94;94;94;122;110;110;86;86 108;84;102;102;102;126;116;116;92;92 18855659 Evaluating the role of etravirine in the second-line antiretroviral therapy after failing an initial non-nucleoside reverse transcriptase inhibitor-based regimen in a resource-limited setting. Patients with 2 etravirine-RAMs. 2008 Current HIV research Abstract HIV K65R;Q151M 55;86 59;91 NRTI 128 132 18855659 Evaluating the role of etravirine in the second-line antiretroviral therapy after failing an initial non-nucleoside reverse transcriptase inhibitor-based regimen in a resource-limited setting. We focused on etravirine-RAMs previously described: V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, and G190A/S. 2008 Current HIV research Abstract HIV A98G;G190A;G190S;K101E;K101P;L100I;V106I;V179D;V179F;V90I;Y181C;Y181I;Y181V 58;111;111;71;71;64;80;87;87;52;96;96;96 62;118;118;78;78;69;85;94;94;56;105;105;105 18855969 Optimization of 5-aryloxyimidazole non-nucleoside reverse transcriptase inhibitors. Herein we present the optimization of a series of 5-aryloxy imidazoles, which possess a balanced pharmacological profile against both wild-type enzyme and the clinically relevant mutations K103N and Y181C. 2008 ChemMedChem Abstract HIV K103N;Y181C 189;199 194;204 18935781 HIV drug resistance tendencies in Latvia. As majority of treatment-naive cases (89%) in this study were with HIV-1 subtypes A or AE, we excluded A62V mutation and estimated RAMs prevalence in group of treatment-naive HIV-infected individuals as 7%. 2008 Central European journal of public health Abstract HIV A62V 103 107 HIV infections 175 187 18935781 HIV drug resistance tendencies in Latvia. By many authors A62V is supposed to be a result of polymorphism in RT gene and is excluded from the list of resistance mutations. 2008 Central European journal of public health Abstract HIV A62V 16 20 RT 67 69 18935781 HIV drug resistance tendencies in Latvia. High prevalence of A62V is typical for HIV-1 subtype A. 2008 Central European journal of public health Abstract HIV A62V 19 23 18935781 HIV drug resistance tendencies in Latvia. In most cases it was NRTI mutation A62V that is associated with multinucleoside resistance caused by Q151M, its effect in the absence of Q151M is not known. 2008 Central European journal of public health Abstract HIV A62V;Q151M;Q151M 35;101;137 39;106;142 NRTI 21 25 18935781 HIV drug resistance tendencies in Latvia. In the group of NRTI mutations M184V (26/75; 34.6%), A62V (12/75; 16.0%) and T215Y (8/75; 10.6%), in NNRTI mutations K103N (10/75; 13.3%), G190S (6/75; 8.0%), in PI group mutations L90M (6/75; 8.0%) and M461/L (6/75; 8.0%) occurred most frequently. 2008 Central European journal of public health Abstract HIV A62V;G190S;K103N;L90M;M184V;T215Y 53;139;117;181;31;77 57;144;122;185;36;82 NNRTI;NRTI;PI 101;16;162 106;20;164 18935781 HIV drug resistance tendencies in Latvia. The origin of predominated mutation A62V associated with NRTI at present is not clear. 2008 Central European journal of public health Abstract HIV A62V 36 40 NRTI 57 61 18945768 Functional consequences of human immunodeficiency virus escape from an HLA-B*13-restricted CD8+ T-cell epitope in p1 Gag protein. A significant reduction in ribosomal frameshifting efficiency was observed with I437M, suggesting that this mechanism contributes to the observed reduced fitness of this virus. 2009 Journal of virology Abstract HIV I437M 80 85 18945768 Functional consequences of human immunodeficiency virus escape from an HLA-B*13-restricted CD8+ T-cell epitope in p1 Gag protein. Examination of the patterns of protein synthesis indicated that the loss of fitness in the I437L and I437M mutants is associated with the accumulation of unprocessed Gag precursors. 2009 Journal of virology Abstract HIV I437L;I437M 91;101 96;106 Gag 166 169 18945768 Functional consequences of human immunodeficiency virus escape from an HLA-B*13-restricted CD8+ T-cell epitope in p1 Gag protein. We demonstrated that substitutions I437L and I437M largely abrogate CTL recognition and reduce viral fitness while variants K436R and I437V have only a marginal effect on recognition and fitness. 2009 Journal of virology Abstract HIV I437L;I437M;I437V;K436R 35;45;134;124 40;50;139;129 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. Binding of APV and Ac-PEP is most sensitive to the D25N mutation, as shown by DeltaT(m) ratios [DeltaT(m)(PR)/DeltaT(m)(PR(D25N))] of 35.8 and 16.3, respectively, whereas binding of DMP323 and RPB (DeltaT(m) ratios of 1-2) is least affected. 2009 Proteins Abstract HIV D25N;D25N 51;123 55;127 PR;PR 106;120 108;122 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. Binding of the substrate-like inhibitors RPB and Ac-PEP is nearly abolished (DeltaT(m)(PR)/DeltaT(m)(PR(D29N)) > or = 44) by the D29N mutation, whereas this mutation only moderately affects binding of the smaller inhibitors (DeltaT(m) ratios of 1.4-2.2). 2009 Proteins Abstract HIV D29N;D29N 104;129 108;133 PR;PR 87;101 89;103 18954404 Identification of human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains in United States blood donors. Drug resistance profiles obtained for 18 donors identified one strain with protease mutation L90M that confers resistance to nelfinavir and one with RT mutation Y188H that confers resistance to nevirapine. 2009 Transfusion Abstract HIV L90M;Y188H 93;161 97;166 PR;RT 75;149 83;151 18954921 Novel modifications in the series of O-(2-phthalimidoethyl)-N-substituted thiocarbamates and their ring-opened congeners as non-nucleoside HIV-1 reverse transcriptase inhibitors. Compound 56 combined the highest activity so far identified against Y181C (EC(50)=1.3 microM) with good potency against the K103R mutant (EC(50)=4.8 microM). 2009 European journal of medicinal chemistry Abstract HIV K103R;Y181C 124;68 129;73 18954921 Novel modifications in the series of O-(2-phthalimidoethyl)-N-substituted thiocarbamates and their ring-opened congeners as non-nucleoside HIV-1 reverse transcriptase inhibitors. Twenty-two C-TCs displayed nanomolar activity against wild-type HIV-1 and a number of analogues were effective against the Y181C mutant. 2009 European journal of medicinal chemistry Abstract HIV Y181C 123 128 18955518 GRL-02031, a novel nonpeptidic protease inhibitor (PI) containing a stereochemically defined fused cyclopentanyltetrahydrofuran potent against multi-PI-resistant human immunodeficiency virus type 1 in vitro. GRL-02031 was potent against a variety of HIV-1(NL4-3)-based molecular infectious clones containing a single primary mutation reported previously or a combination of such mutations, although it was slightly less active against HIV-1 variants containing consecutive amino acid substitutions: M46I and I47V or I84V and I85V. 2009 Antimicrobial agents and chemotherapy Abstract HIV I47V;I84V;I85V;M46I 300;308;317;291 304;312;321;295 18955518 GRL-02031, a novel nonpeptidic protease inhibitor (PI) containing a stereochemically defined fused cyclopentanyltetrahydrofuran potent against multi-PI-resistant human immunodeficiency virus type 1 in vitro. Upon selection of HIV-1(NL4-3) in the presence of GRL-02031, mutants carrying L10F, L33F, M46I, I47V, Q58E, V82I, I84V, and I85V in the protease-encoding region and G62R (within p17), L363M (p24-p2 cleavage site), R409K (within p7), and I437T (p7-p1 cleavage site) in the gag-encoding region emerged. 2009 Antimicrobial agents and chemotherapy Abstract HIV G62R;I437T;I47V;I84V;I85V;L10F;L33F;L363M;M46I;Q58E;R409K;V82I 165;237;96;114;124;78;84;184;90;102;214;108 169;242;100;118;128;82;88;189;94;106;219;112 PR;p24;Gag 136;191;272 144;194;275 18974494 High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome. Mutation K103N was observed in 56% (14/25) of the children while mutation T215Y was found in none. 2008 Indian journal of medical microbiology Abstract HIV K103N;T215Y 9;74 14;79 18974494 High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome. Mutations T215Y and K103N were detected by a nested cum amplification refractory mutation system polymerase chain reaction (ARMS PCR) and the results were confirmed by direct sequencing in five randomly selected cases. 2008 Indian journal of medical microbiology Abstract HIV K103N;T215Y 20;10 25;15 Pol 97 107 18974494 High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome. Two of the six drug naive children also showed K103N mutation. 2008 Indian journal of medical microbiology Abstract HIV K103N 47 52 18981781 Phenotypic impact of resistance mutations on etravirine susceptibility in HIV patients with prior failure to nonnucleoside analogues. Two novel changes, K101H and E399D, significantly diminished etravirine susceptibility. 2008 AIDS (London, England) Abstract HIV E399D;K101H 29;19 34;24 18981781 Phenotypic impact of resistance mutations on etravirine susceptibility in HIV patients with prior failure to nonnucleoside analogues. Y181C in combination with at least one etravirine resistance-associated mutation caused, on average, a 12.6-fold reduced susceptibility to etravirine. 2008 AIDS (London, England) Abstract HIV Y181C 0 5 18984007 Non-nucleoside HIV-1 reverse transcriptase inhibitors di-halo-indolyl aryl sulfones achieve tight binding to drug-resistant mutants by targeting the enzyme-substrate complex. By comparing the activities of the different compounds against wild-type RT and the resistant enzymes carrying the single mutations Lys103Asn, Leu100Ile, and Tyr181Ile (K103N, L100I, and Y181I), we found that one compound (RS1914) dissociated from the mutated enzymes almost 10-fold slower than from the wild type RT. 2009 Antiviral research Abstract HIV K103N;K103N;L100I;L100I;Y181I;Y181I 132;169;143;176;158;187 141;174;152;181;167;192 RT;RT 73;314 75;316 18987155 Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane gp41 protein as a distinct determinant for viral infection. Both T20 and L43L peptides derived from the two gp41 extracellular C- and N-terminal alpha-helical heptad repeats, respectively, inhibited WT and DeltaLWYIK Env-mediated viral entry with comparable efficacies. 2009 Journal of virology Abstract HIV L43L 13 17 gp41;Env 48;157 52;160 18987460 Low prevalence of drug-resistant HIV-1 in patients newly diagnosed with early stage of HIV infection in Korea. The resistant mutation of reverse-transcriptase gene was found at E44D, and the major resistant mutation of protease gene was found at M46L. 2008 The Tohoku journal of experimental medicine Abstract HIV E44D;M46L 66;135 70;139 RT;PR 26;108 47;116 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In treated patients, K20M, D30N, G73S, I84V, and L90M, were more prevalent in subtype B, and K20T and N88S were more prevalent in subtype F1. 2009 Infection, genetics and evolution Abstract HIV D30N;G73S;I84V;K20M;K20T;L90M;N88S 27;33;39;21;93;49;102 31;37;43;25;97;53;106 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In untreated patients, mutations L10V, K20R, and M36I were more frequent in subtype F1, while L63P, A71T, and V77I were more prevalent in subtype B. 2009 Infection, genetics and evolution Abstract HIV A71T;K20R;L10V;L63P;M36I;V77I 100;39;33;94;49;110 104;43;37;98;53;114 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. V82L mutation was present with increased frequency in isolates from children compared to isolates from adults infected with both subtypes. 2009 Infection, genetics and evolution Abstract HIV V82L 0 4 19000027 HIV type 1 subtype C drug resistance among pediatric and adult South African patients failing antiretroviral therapy. K103N (25%), V106M (20%), and G190A (17%) were found among patients failing nevirapine- or efavirenz-containing regimens. 2008 AIDS research and human retroviruses Abstract HIV G190A;V106M;K103N 30;13;0 35;18;5 19000027 HIV type 1 subtype C drug resistance among pediatric and adult South African patients failing antiretroviral therapy. Ninety-one percent of patients harbored resistance mutations; the most frequent NRTI mutations were M184V/I (37%), D67N (32%), T215Y/F (25%), K70R (21%), M41L (20%), K219Q/E (14%), and K65R (14%), reflecting the frequent use of lamuvidine and zidovudine. 2008 AIDS research and human retroviruses Abstract HIV D67N;K219E;K219Q;K65R;K70R;M184I;M184V;M41L;T215F;T215Y 115;166;166;185;142;100;100;154;127;127 119;173;173;189;146;107;107;158;134;134 NRTI 80 84 19000027 HIV type 1 subtype C drug resistance among pediatric and adult South African patients failing antiretroviral therapy. Of the patients who received PIs, the most common mutations were V82A/T (12%), M46I (11%), and L90M (8%). 2008 AIDS research and human retroviruses Abstract HIV L90M;M46I;V82A;V82T 95;79;65;65 99;83;71;71 PI 29 32 19004651 A docking study of L-chicoric acid with HIV-1 integrase. Analysis of the interactions with key IN residues, combined with results using a L-CA tetraacetylated derivative and a Q148A IN mutant, correlate well with the experimental data. 2009 Journal of molecular graphics & modelling Abstract HIV Q148A 119 124 IN;IN;Capsid 38;125;83 40;127;85 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. In clade B samples, there was a very strong relationship between the silent mutations and the thymidine analogue mutations, in particular D67N. 2008 AIDS (London, England) Abstract HIV D67N 138 142 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. METHODS: A comparison of the reverse transcriptase gene, from antiretroviral- naive (N = 812) and experienced individuals (N = 2212), reveals two silent mutations (K65K and K66K) that are strongly associated with treatment experience. 2008 AIDS (London, England) Abstract HIV K65K;K66K 164;173 169;177 RT 29 50 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Steady-state kinetic experiments demonstrated that HIV-1 reverse transcriptase exhibited a strong tendency to pause and/or dissociate at codons 65 and 66 on RNA templates that contained the D67N and K70R mutations. 2008 AIDS (London, England) Abstract HIV D67N;K70R 190;199 194;203 RT 57 78 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. The transmission of nucleoside analogue mutations and 215 resistant variants (T215C/D/I/F/N/S/Y) declined with clustering (7.9 vs. 2008 AIDS (London, England) Abstract HIV T215C;T215D;T215F;T215I;T215N;T215S;T215Y 78;78;78;78;78;78;78 95;95;95;95;95;95;95 19012571 Revealing interaction mode between HIV-1 reverse transcriptase and diaryltriazine analog inhibitor. Lys103Asn (K103N) mutant frequently is observed in HIV-1 reverse transcriptase. 2008 Chemical biology & drug design Abstract HIV K103N;K103N 0;11 9;16 RT 57 78 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Furthermore, we observed that VSV-G-pseudotyped HIV-1 containing these IN mutants was unable to replicate in the C8166 T cell line and this defect was partially rescued by complementation with the catalytically inactive D64E IN mutant. 2008 Retrovirology Abstract HIV D64E 220 224 IN;IN 71;225 73;227 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. RESULTS: Our study identified three HIV-1 IN mutants, V165A, A179P and KR186,7AA, located in the C-terminal region of the catalytic core domain of IN that do not induce the lethal phenotype in yeast. 2008 Retrovirology Abstract HIV A179P;V165A 61;54 66;59 IN;IN 42;147 44;149 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. This hypothesis is supported by the in vitro activity phenotype of HIV-1 IN mutant, with a K219S substitution showing loss in strand transfer activity while maintaining 3' processing on an HIV-1 substrate. 2009 Journal of molecular biology Abstract HIV K219S 91 96 IN 73 75 19018669 High-affinity binding of southern African HIV type 1 subtype C envelope protein, gp120, to the CCR5 coreceptor. All gp120 proteins bound to CD4-expressing cells, except one, 97ZA347ts, which had Arg substituted for the Cys239 in the conserved C2 loop. 2008 AIDS research and human retroviruses Abstract HIV R239C 83 113 gp120 4 9 19019404 Mutations at human immunodeficiency virus type 1 reverse transcriptase tryptophan repeat motif attenuate the inhibitory effect of efavirenz on virus production. Our results indicate that even though alanine substitutions at W401 (W401A) or at both W401 and W402 (W401A/W402A) have no major effect on steady-state virus processing, the combined W401A/W402A mutations partially negate and the W401A mutation almost completely negates an efavirenz (EFV)-imposed barrier to virus production. 2009 Virology Abstract HIV W401A;W401A;W401A;W401A;W402A;W402A 69;102;183;230;108;189 74;107;188;235;113;194 19019404 Mutations at human immunodeficiency virus type 1 reverse transcriptase tryptophan repeat motif attenuate the inhibitory effect of efavirenz on virus production. We also found that an artificial p66RT carrying the W401A or W401A/W402A mutations was packaged into virions more efficiently than wild-type p66RT, and that the viral incorporation of p66RT is significantly reduced by EFV, implying a novel effect of EFV on RT-Gag interaction. 2009 Virology Abstract HIV W401A;W401A;W402A 52;61;67 57;66;72 Gag;RT 260;257 263;259 19019971 In vivo fitness cost of the M184V mutation in multidrug-resistant human immunodeficiency virus type 1 in the absence of lamivudine. Lamivudine therapy selects for the M184V mutation. 2009 Journal of virology Abstract HIV M184V 35 40 19019971 In vivo fitness cost of the M184V mutation in multidrug-resistant human immunodeficiency virus type 1 in the absence of lamivudine. We used quantitative allele-specific PCR to precisely calculate the fitness differences between the mutated M184V virus and one that had reverted to the wild type in a cohort of patients by selectively interrupting reverse transcriptase inhibitor therapy, and we found that the M184V variants were consistently 4 to 8% less fit than the wild type in the absence of drug. 2009 Journal of virology Abstract HIV M184V;M184V 108;278 113;283 RT 215 236 19020013 NMDA receptor activation by HIV-Tat protein is clade dependent. The Cys 30-Cys 31 motif in Tat is critical for exciting the NMDA receptor and the Cys31Ser mutation found in clade C Tat has a significantly attenuated neurotoxic response. 2008 The Journal of neuroscience Abstract HIV C31S 82 90 Tat;Tat 27;117 30;120 19024630 Binding modes of two novel non-nucleoside reverse transcriptase inhibitors, YM-215389 and YM-228855, to HIV type-1 reverse transcriptase. A single amino acid substitution confers only moderate resistance to YM-215389; indeed, four amino acid substitutions (V106L, V108I, E138K and L214F) were necessary for high-level resistance. 2008 Antiviral chemistry & chemotherapy Abstract HIV E138K;L214F;V106L;V108I 133;143;119;126 138;148;124;131 19024630 Binding modes of two novel non-nucleoside reverse transcriptase inhibitors, YM-215389 and YM-228855, to HIV type-1 reverse transcriptase. Although the activity of YM-228855, a derivative of YM-215389 that has two bulky and rigid cyano-moieties on the benzene ring, was 10x more potent against HIV-1 than YM-215389, its anti-HIV-1 activity was readily reduced with single substitutions as with Y181I and K103N. 2008 Antiviral chemistry & chemotherapy Abstract HIV K103N;Y181I 265;255 270;260 19024630 Binding modes of two novel non-nucleoside reverse transcriptase inhibitors, YM-215389 and YM-228855, to HIV type-1 reverse transcriptase. BACKGROUND: YM-215389 and YM-228855 are thiazolidenebenzenesulfonamide (TBS) derivatives and novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) that inhibit not only wild-type, but also the K103N- and Y181C-substituted reverse transcriptase (RT) of HIV type-1 (HIV-1). 2008 Antiviral chemistry & chemotherapy Abstract HIV K103N;Y181C 202;213 207;218 NNRTI;RT;NNRTI;RT 99;231;148;254 135;252;154;256 19027039 Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. In contrast, Q148K/G140S and Q148R/E138K had nearly equivalent or slightly reduced fold resistance to the INI compared with their respective Q148 primary mutants, and had increases in infectivity and replication kinetics. 2009 Antiviral research Abstract HIV E138K;G140S;Q148K;Q148R 35;19;13;29 40;24;18;34 IN 106 109 19027039 Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Integrase-resistant mutations Q148K and Q148R were identified as primary mutations with the passage of HIV-1 IIIB in the presence of INIs S-1360 or S/GSK-364735, respectively. 2009 Antiviral research Abstract HIV Q148K;Q148R 30;40 35;45 IN;IN 0;133 9;137 19027039 Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Relative to Q148K alone, Q148K/E138K had 2- and >6-fold increases in resistance to S-1360 and S/GSK-364735, respectively, and the double mutant had slightly better infectivity and replication kinetics. 2009 Antiviral research Abstract HIV E138K;Q148K;Q148K 31;12;25 36;17;30 19027039 Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Secondary amino acid substitutions E138K or G140S were observed when passage with INI was continued. 2009 Antiviral research Abstract HIV E138K;G140S 35;44 40;49 IN 82 85 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. Sequence analysis indicates that the site-directed changes were stable during the first three weeks after inoculation but thereafter the S147A amino acid substitution changed to a threonine in two of three macaques. 2009 Virology Abstract HIV S147A 137 142 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. The L148A substitution remained stable in the vif amplified from the PBMC of all three macaques. 2009 Virology Abstract HIV L148A 4 9 Vif 46 49 19031460 Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine. Among quadruple ART patients, who all were treated at primary HIV-1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild-type virus at baseline. 2009 Journal of medical virology Abstract HIV M184V 106 111 19031460 Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine. In patients on dual therapy, M184I/V mutants were found frequently. 2009 Journal of medical virology Abstract HIV M184I;M184V 29;29 36;36 19031460 Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine. In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment-naive HIV-1 infected patients receiving antiretroviral therapy (ART) was examined. 2009 Journal of medical virology Abstract HIV M184I;M184V 80;80 87;87 RT 58 79 HIV infections 163 177 19031460 Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine. Plasma virus from three cohorts of treatment-naive patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine-containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real-time PCR method. 2009 Journal of medical virology Abstract HIV M184I;M184V 168;168 175;175 19031460 Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or four-drug combination, in contrast to those receiving a less potent regimen. 2009 Journal of medical virology Abstract HIV M184I;M184V 13;13 20;20 19032066 Short communication: Different mutation patterns in subtype CRF06_cpx after mother-to-child transmission. Genotypic resistance tests (GRT) during follow-up showed selection of M184V/L283I in reverse transcriptase (RT) and H63Q/A71V/L90M in protease (PR). 2008 AIDS research and human retroviruses Abstract HIV A71V;H63Q;L90M;L283I;M184V 121;116;126;76;70 125;120;130;81;75 RT;PR;PR;RT 85;134;144;108 106;142;146;110 19032066 Short communication: Different mutation patterns in subtype CRF06_cpx after mother-to-child transmission. GRT during follow-up showed selection of L74V/K103N/M184V/M230L in RT and M46I/H63Q/N88S in PR. 2008 AIDS research and human retroviruses Abstract HIV H63Q;K103N;L74V;M184V;M230L;M46I;N88S 79;46;41;52;58;74;84 83;51;45;57;63;78;88 PR;RT 92;67 94;69 19032103 Sensitivity of phenotypic susceptibility analyses for nonthymidine nucleoside analogues conferred by K65R or M184V in mixtures with wild-type HIV-1. Phenotypic resistance masking by wild-type virus may explain this discrepancy.Consistent with this notion were (1) the presence of low level nucleoside reverse-transcriptase inhibitor-resistant human immunodeficiency virus in subjects receiving failing first-line regimens consisting of tenofovir (TDF), abacavir (ABC), and lamivudine (3TC); (2) lower fold resistance associated with mixtures versus mutants in a clinical-isolate database; and (3) dose dependent changes in susceptibility to ABC, 3TC, TDF, and didanosine on titration of K65R and/or M184V with wild-type virus. 2009 The Journal of infectious diseases Abstract HIV K65R;M184V 538;550 542;555 NRTI 141 173 19036752 High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. 2009 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184I;M184V 97;80;80 101;87;87 NNRTI 123 128 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. CONCLUSIONS: This study suggests that the use of certain TDF-based regimens caused the increase in K65R incidence over the last years. 2009 Infection, genetics and evolution Abstract HIV K65R 99 103 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. In this study, we evaluated the impact of these combinations on K65R selection over time. 2009 Infection, genetics and evolution Abstract HIV K65R 64 68 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. Incidence of K65R was calculated and compared with proportions of failing therapies in the respective year of sampling including TDF or didanosine plus stavudine and their respective frequency of K65R selection were analyzed using classical statistics and Bayesian Network Learning. 2009 Infection, genetics and evolution Abstract HIV K65R;K65R 13;196 17;200 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. OBJECTIVE: The overall prevalence of the K65R mutation in HIV-1 reverse transcriptase has increased in treatment-experienced patients, mostly attributed to the increasing use of tenofovir (TDF). 2009 Infection, genetics and evolution Abstract HIV K65R 41 45 RT 64 85 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. RESULTS: The overall rate of K65R in the database was consistent with earlier reports. 2009 Infection, genetics and evolution Abstract HIV K65R 29 33 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. The incidence of K65R increased in the period 2002-2004 but showed a sharp, significant decrease in 2005, despite a continuous increase of patients failing TDF-based regimens. 2009 Infection, genetics and evolution Abstract HIV K65R 17 21 19038365 The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir. The proportion of patients failing certain not-recommended regimens decreased sharply in 2005 and therefore correlated well with K65R incidence trend. 2009 Infection, genetics and evolution Abstract HIV K65R 129 133 19040279 PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. Analysis of p55Gag processing showed that a marked defect in protease activity caused by mutation P81S could only be compensated when K45R and M46I were present. 2008 Journal of medical virology Abstract HIV K45R;M46I;P81S 134;143;98 138;147;102 PR 61 69 19040279 PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. Four mutations in protease (PR) were selected after 25 weeks: two flap mutations (K45R and M46I) and two novel active site mutations (T80I and P81S). 2008 Journal of medical virology Abstract HIV K45R;M46I;P81S;T80I 82;91;143;134 87;95;147;139 PR;PR 18;28 26;30 19040279 PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. In contrast, the P81S mutation alone caused hypersensitivity to two other PIs, saquinavir (SQV) and nelfinavir (NFV). 2008 Journal of medical virology Abstract HIV P81S 17 21 PI 74 77 19043929 Variability in the plasma concentration of efavirenz and nevirapine is associated with genotypic resistance after treatment interruption. Emergence of resistant variants (including K103N, Y181C or G190S) after interruption was associated with a higher coefficient of variation in NNRTI plasma concentrations during the treatment period. 2008 Antiviral therapy Abstract HIV G190S;K103N;Y181C 59;43;50 64;48;55 NNRTI 142 147 19043929 Variability in the plasma concentration of efavirenz and nevirapine is associated with genotypic resistance after treatment interruption. Moreover, minority HIV-1 variants containing different resistance patterns (V1061/A, K103R/E or Y188C/D/H) were detected regardless of NNRTI concentrations. 2008 Antiviral therapy Abstract HIV K103E;K103R;Y188C;Y188D;Y188H 85;85;96;96;96 92;92;105;105;105 NNRTI 135 140 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. BACKGROUND: Very little is known about the alternative L74I mutation. 2009 AIDS (London, England) Abstract HIV L74I 55 59 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. CONCLUSIONS: This study shows that the L74I and the L74V correspond to two different mutation pathways, conferring probably different resistance and replication advantages on HIV depending on the context. 2009 AIDS (London, England) Abstract HIV L74I;L74V 39;52 43;56 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. Didanosine plays the principal role in the L74V emergence. 2009 AIDS (London, England) Abstract HIV L74V 43 47 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. METHODS: We focused on the treatment used at the exact time of any L74V or L74I emergences in 74 patients, and we compared the use of each nucleoside reverse transcriptase inhibitor (NRTI) separately and in combination between the 74I and the 74V groups. 2009 AIDS (London, England) Abstract HIV L74I;L74V 75;67 79;71 NRTI;NRTI 139;183 171;187 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. OBJECTIVE: To compare and clarify the role of each antiretroviral compound and the resistance background in the emergence of the L74I and L74V mutations. 2009 AIDS (London, England) Abstract HIV L74I;L74V 129;138 133;142 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. RESULTS: A majority of L74I mutations is selected under the zidovudine plus abacavir combination or under tenofovir with thymidine analogue mutations in the resistance background. 2009 AIDS (London, England) Abstract HIV L74I 23 27 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. Taking into account more systematically the L74I mutation, whose impact is certainly currently underestimated, would increase our understanding of this substitution and its effects on the drug activity in vivo. 2009 AIDS (London, England) Abstract HIV L74I 44 48 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. The K103N substitution also plays an important role in the L74I emergence when not associated with the other non-NRTI mutations seen in this study: L100I, G190A and Y181C. 2009 AIDS (London, England) Abstract HIV G190A;K103N;L100I;L74I;Y181C 155;4;148;59;165 160;9;153;63;170 NNRTI 109 117 19050391 Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. This lack of knowledge has led to contradictory and confusing attitudes to L74I; although this mutation is not listed by the International AIDS Society - USA, it is increasingly included in several resistance algorithms. 2009 AIDS (London, England) Abstract HIV L74I 75 79 AIDS 139 143 19058881 Parallel synthesis, molecular modelling and further structure-activity relationship studies of new acylthiocarbamates as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Several ATCs were active at micromolar concentrations against HIV-1 strains carrying the RT Y181C mutation and one of them was also moderately active against the K103R variant. 2009 European journal of medicinal chemistry Abstract HIV K103R;Y181C 162;92 167;97 RT 89 91 19064892 Nucleoside and nucleotide analogs select in culture for different patterns of drug resistance in human immunodeficiency virus types 1 and 2. In agreement with our previous findings, dual-drug combinations of TFV, ddI, ABC, d4T, ZDV, and 3TC preferentially selected for K65R in HIV-1 subtype C isolates. 2009 Antimicrobial agents and chemotherapy Abstract HIV K65R 128 132 19064892 Nucleoside and nucleotide analogs select in culture for different patterns of drug resistance in human immunodeficiency virus types 1 and 2. In contrast, selections with all four HIV-2 cultures favored the development of M184I in dual-drug combinations that included either 3TC or FTC. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184I 80 85 19064892 Nucleoside and nucleotide analogs select in culture for different patterns of drug resistance in human immunodeficiency virus types 1 and 2. In HIV-1 subtype B, TFV-3TC and ZDV-3TC selected for M184I and D67N, respectively. 2009 Antimicrobial agents and chemotherapy Abstract HIV D67N;M184I 63;53 67;58 19064892 Nucleoside and nucleotide analogs select in culture for different patterns of drug resistance in human immunodeficiency virus types 1 and 2. Recent findings suggest bidirectional antagonisms between the K65R mutation and thymidine analogue mutations in human immunodeficiency virus type 1 (HIV-1)-infected, treatment-experienced patients, yet little is known about HIV-2 in this regard. 2009 Antimicrobial agents and chemotherapy Abstract HIV K65R 62 66 19064892 Nucleoside and nucleotide analogs select in culture for different patterns of drug resistance in human immunodeficiency virus types 1 and 2. Since HIV-2 cultures did not develop K65R, an ultrasensitive allele-specific real-time PCR assay was developed to distinguish the presence of 65R from wild-type K65 after 16 cycles with a discriminatory ability of 0.1% against a population of wild-type virus. 2009 Antimicrobial agents and chemotherapy Abstract HIV K65R 37 41 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Furthermore, competition binding assays suggest that Q509L decreases the affinity of the enzyme to bind T/P with duplex lengths less than 18 nucleotides in the polymerase-independent RNase H cleavage mode, while not affecting the enzyme's affinity to bind the same T/P in an AZT-MP excision competent mode. 2008 Biochemistry Abstract HIV Q509L 53 58 Pol 160 170 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In the current study, we have defined the mechanism by which Q509L confers AZT resistance by performing in-depth biochemical analyses of wild type, D67N/K70R/T215F and D67N/K70R/T215F/Q509L HIV-1 RT. 2008 Biochemistry Abstract HIV D67N;D67N;K70R;K70R;Q509L;T215F;T215F;Q509L 148;168;153;173;184;158;178;61 152;172;157;177;189;163;183;66 RT 196 198 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Our results show that Q509L increases AZT-monophosphate (AZT-MP) excision activity of RT on RNA/DNA template/primers (T/Ps) but not DNA/DNA T/Ps. 2008 Biochemistry Abstract HIV Q509L 22 27 RT 86 88 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Presteady-state kinetic analyses indicate that Q509L does not affect initial rates of the polymerase-directed RNase H activity but only polymerase-independent cleavages that occur after a T/P dissociation event. 2008 Biochemistry Abstract HIV Q509L 47 52 Pol;Pol 90;136 100;146 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. This increase in excision activity on the RNA/DNA T/P is due to Q509L decreasing a secondary RNase H cleavage event that reduces the RNA/DNA duplex length to 10 nucleotides and significantly impairs the enzyme's ability to excise the chain-terminating nucleotide. 2008 Biochemistry Abstract HIV Q509L 64 69 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. We recently reported that zidovudine (AZT) selected for the Q509L mutation in the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT), which increases resistance to AZT in combination with the thymidine analogue mutations D67N, K70R, and T215F. 2008 Biochemistry Abstract HIV D67N;K70R;Q509L;T215F 238;244;60;254 242;248;65;259 RT;RT 123;146 144;148 19069789 [Molecular genetic characteristics of HIV-1 variants circulating in Cherepovets, Vologda region: the second case of the epidemic outbreak caused by the recombinant gagAenvB]. Amongst the IDU-A strains, there were genotypes containing characteristic secondary drug resistance mutations in the pol gene of V771 and A62V, as well as variants of the wild type. 2008 Voprosy virusologii Abstract HIV A62V 138 142 Pol 117 120 19070880 Role of capsid sequence and immature nucleocapsid proteins p9 and p15 in Human Immunodeficiency Virus type 1 genomic RNA dimerization. To identify the minimum level of protease activity compatible with a WT level of gRNA dimers, we introduced mutations Thr26Ser and Ala28Ser in the viral protease to partially inactivate it, and we prepared composite HIV-1 resulting from the cotransfection of various ratios of WT and protease-inactive proviral DNAs. 2009 Virology Abstract HIV A28S;T26S 131;118 139;126 PR;PR;PR 33;153;284 41;161;292 19073602 Interactions of HIV-1 inhibitory peptide T20 with the gp41 N-HR coiled coil. By contrast, mutations near the T20 N terminus substantially influenced inhibitor binding strength. 2009 The Journal of biological chemistry Abstract HIV T20N 32 37 19073602 Interactions of HIV-1 inhibitory peptide T20 with the gp41 N-HR coiled coil. Mutating three aromatic residues at the T20 C terminus (WNWF --> ANAA) had no effect on affinity, suggesting that these amino acids do not participate in T20 binding to the gp41 N-HR. 2009 The Journal of biological chemistry Abstract HIV T20C 40 45 gp41 173 177 19073602 Interactions of HIV-1 inhibitory peptide T20 with the gp41 N-HR coiled coil. We used 5H-ex to investigate how the T20 N and C termini contributed to the inhibitor binding activity. 2009 The Journal of biological chemistry Abstract HIV T20N 37 42 19073606 Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. Circular dichroism analysis revealed that the S138A provided increased stability of the 6-helix bundle. 2009 The Journal of biological chemistry Abstract HIV S138A 46 51 19073606 Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. However, prolonged therapies with T-20 result in the emergence of T-20-resistant strains that contain primary mutations such as N43D in the N-HR of gp41 (where T-20 and C-HR bind) that help the virus escape at a fitness cost. 2009 The Journal of biological chemistry Abstract HIV N43D 128 132 gp41 148 152 19073606 Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. In this case, we designed a variant of C34 with the secondary escape mutation N126K and showed that it can effectively inhibit replication of C34-resistant HIV-1. 2009 The Journal of biological chemistry Abstract HIV N126K 78 83 19073606 Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. Such variants often go on to acquire a secondary mutation, S138A, in the C-HR of gp41 region that corresponds to the sequence of T-20. 2009 The Journal of biological chemistry Abstract HIV S138A 59 64 gp41 81 85 19073606 Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. To preempt this escape strategy, we designed a modified T-20 variant containing the S138A substitution and showed that it is a potent inhibitor of both T-20-sensitive and T-20-resistant viruses. 2009 The Journal of biological chemistry Abstract HIV S138A 84 89 19073606 Design of peptide-based inhibitors for human immunodeficiency virus type 1 strains resistant to T-20. We demonstrate here that the role of S138A is to compensate for the impaired fusion kinetics of HIV-1s carrying primary mutations that abrogate binding of T-20. 2009 The Journal of biological chemistry Abstract HIV S138A 37 42 19073730 Template usage is responsible for the preferential acquisition of the K65R reverse transcriptase mutation in subtype C variants of human immunodeficiency virus type 1. Template factors can therefore increase the probability of K65R development in subtype C HIV-1. 2009 Journal of virology Abstract HIV K65R 59 63 19073730 Template usage is responsible for the preferential acquisition of the K65R reverse transcriptase mutation in subtype C variants of human immunodeficiency virus type 1. We propose that a nucleotide template-based mechanism facilitates the acquisition of the K65R mutation in subtype C human immunodeficiency virus type 1 (HIV-1). 2009 Journal of virology Abstract HIV K65R 89 93 19073730 Template usage is responsible for the preferential acquisition of the K65R reverse transcriptase mutation in subtype C variants of human immunodeficiency virus type 1. When subtype C reverse transcriptase (RT) was employed to synthesize DNA from subtype C DNA templates, preferential pausing was seen at the nucleotide position responsible for the AAG-to-AGG K65R mutation. 2009 Journal of virology Abstract HIV K65R 191 195 RT;RT 15;38 36;40 19073742 Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D. HIV-1 A92E and G94D capsid escape mutants arise during CypA inhibition and in certain cell lines are dependent on CypA inhibition. 2009 Journal of virology Abstract HIV G94D 15 19 Capsid 20 26 19075055 Virologic failure in first-line human immunodeficiency virus therapy with a CCR5 entry inhibitor, aplaviroc, plus a fixed-dose combination of lamivudine-zidovudine: nucleoside reverse transcriptase inhibitor resistance regardless of envelope tropism. The acquisition of the M184V mutation is the primary characteristic of virologic failure in first-line therapy with aplaviroc plus lamivudine-zidovudine, regardless of the envelope tropism. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184V 23 28 Env 172 180 19075055 Virologic failure in first-line human immunodeficiency virus therapy with a CCR5 entry inhibitor, aplaviroc, plus a fixed-dose combination of lamivudine-zidovudine: nucleoside reverse transcriptase inhibitor resistance regardless of envelope tropism. The majority of the subjects with virologic failure (six of eight) acquired the lamivudine resistance-associated mutation M184V, and none had evidence of reduced susceptibility to aplaviroc at the time of virologic failure, even at the clonal level. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184V 122 127 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. mtDNA abundance significantly decreased in Y955C TG, increased in TK2 native and I212N TGs, and was unchanged in H121N TGs at 10 weeks regardless of treatment. 2009 Laboratory investigation; a journal of technical methods and pathology Abstract HIV H121N;I212N;Y955C 113;81;43 118;86;48 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. TGs included cardiac-specific overexpression of native thymidine kinase 2 (TK2), two pathogenic TK2 mutants (H121N and I212N), and a mutant of mtDNA polymerase, pol-gamma (Y955C). 2009 Laboratory investigation; a journal of technical methods and pathology Abstract HIV H121N;I212N;Y955C 109;119;172 115;124;177 Pol;Pol 149;161 159;164 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Y955C and I212N TGs exhibited LVH during growth irrespective of treatment. 2009 Laboratory investigation; a journal of technical methods and pathology Abstract HIV I212N;Y955C 10;0 15;5 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Y955C TGs exhibited cardiomyopathy (CM) at 3 and 10 weeks irrespective of treatment, whereas H121N and I212N TGs exhibited CM only after 10 weeks AZT-HAART. 2009 Laboratory investigation; a journal of technical methods and pathology Abstract HIV H121N;I212N;Y955C 93;103;0 98;108;5 19086910 Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. 2009 Clinical infectious diseases Abstract HIV M184I;M184V 60;38 65;43 19086910 Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. 2009 Clinical infectious diseases Abstract HIV K103N;K65R;M184I;M184V;Y181C 24;18;49;38;31 29;22;54;43;36 RT;Pol 62;129 83;139 19090525 Structural modifications of DAPY analogues with potent anti-HIV-1 activity. The most active compound showed activity against wild-type HIV-1 with an EC(50) value of 2.35 nM and against the double mutant strain (K103N+Y181C) with an EC(50) value of 6.6 microM, with a selectivity index greater than 60 000 against wild-type HIV-1. 2009 ChemMedChem Abstract HIV K103N;Y181C 135;141 140;146 19092977 Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a systematic review of virologic and biochemical evidence. Mutations not typical of B subtypes include the reverse transcriptase mutation V106M and the protease mutations M89I/V and N83T. 2008 AIDS reviews Abstract HIV M89I;M89V;N83T;V106M 112;112;123;79 118;118;127;84 RT;PR 48;93 69;101 19092977 Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a systematic review of virologic and biochemical evidence. the protease inhibitor mutations I93L and M89I/V. 2008 AIDS reviews Abstract HIV I93L;M89I;M89V 33;42;42 37;48;48 PR 4 12 19092977 Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a systematic review of virologic and biochemical evidence. Virologic and biochemical data suggest that K65R is more likely to emerge in subtype C HIV-1. 2008 AIDS reviews Abstract HIV K65R 44 48 19100236 Fluctuating partially native-like topologies in the acid denatured ensemble of autolysis resistant HIV-1 protease. We report here NMR characterization of the acid-denatured state of a mutant of HIV-1 protease, designed to prevent autolysis (Q7K, L33I, L63I) and to prevent cysteine oxidation (C67A and C95A). 2009 Archives of biochemistry and biophysics Abstract HIV C67A;C95A;L33I;L63I;Q7K 178;187;131;137;126 183;191;135;141;129 PR 85 93 19103115 [Study on the threshold of HIV-1 drug resistance in Hunan province]. RESULTS: A total number of 69 patients whose HIV sequences were amplified successfully with 2 (2.9%) specimens appeared mutations associated with HIV-1 drug resistance in the reverse transcriptase region, including one as V75M and the other one as K103N and V181C. 2008 Zhonghua liu xing bing xue za zhi Abstract HIV K103N;V181C;V75M 248;258;222 253;263;226 RT 175 196 19103117 [Research on the selective kinetics of HIV-1 nucleoside reverse transcriptase inhibitor drug resistance-associated mutations among 4 AIDS patients receiving highly active antiretroviral therapy]. Interestingly, in patient 'C', some clones comprising not only TAMs pattern 1 mutations (T215Y) but also TAMs pattern 2 mutations (K70R, D67N). 2008 Zhonghua liu xing bing xue za zhi Abstract HIV D67N;K70R;T215Y 137;131;89 141;135;94 19103117 [Research on the selective kinetics of HIV-1 nucleoside reverse transcriptase inhibitor drug resistance-associated mutations among 4 AIDS patients receiving highly active antiretroviral therapy]. TAMs pattern 2, including D67N, K70R and K219Q mutations, was discovered in patient 'B'. 2008 Zhonghua liu xing bing xue za zhi Abstract HIV D67N;K219Q;K70R 26;41;32 30;46;36 19103117 [Research on the selective kinetics of HIV-1 nucleoside reverse transcriptase inhibitor drug resistance-associated mutations among 4 AIDS patients receiving highly active antiretroviral therapy]. Typical resistance mutations of thymidine analogue mutations (TAMs) pattern 1, such as L210W, T215Y and M41L, were generated in patient 'A'. 2008 Zhonghua liu xing bing xue za zhi Abstract HIV L210W;M41L;T215Y 87;104;94 92;108;99 19104010 Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase. Together, these mutations conferred 67-fold resistance to GS-9160, indicating that L74M may potentiate the resistance caused by E92V. 2009 Antimicrobial agents and chemotherapy Abstract HIV E92V;L74M 128;83 132;87 19104010 Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase. Viral resistance selections performed with GS-9160 yielded a novel pattern of mutations within the catalytic core domain of IN; E92V emerged initially, followed by L74M. 2009 Antimicrobial agents and chemotherapy Abstract HIV E92V;L74M 128;164 132;168 IN 124 126 19104010 Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase. While E92V as a single mutant conferred 12-fold resistance against GS-9160, L74M had no effect as a single mutant. 2009 Antimicrobial agents and chemotherapy Abstract HIV E92V;L74M 6;76 10;80 19109381 Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein. By comparison to M184V, the magnitude of the reductions in RRC caused by the escape mutations, particularly when coexpressed, suggests that the costs of escape are sufficient to affect in vivo viral dynamics and may thus play a role in the protective effect associated with HLA-B*57/B*5801. 2009 Journal of virology Abstract HIV M184V 17 22 19109381 Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein. Individually, the impact of the escape mutations on RRC was comparable to that of M184V, while coexpression of the mutations resulted in substantial further reductions, with the maximum impact observed for the triple mutant (RRC(P146-G163-N242) = 0.62). 2009 Journal of virology Abstract HIV M184V 82 87 19109381 Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein. To answer the question, the RRCs were quantified for escape mutations in three immunodominant HLA-B*57/B*5801 epitopes in capsid: A146P in IW9 (RRC(P146) = 0.91), A163G in KF11 (RRC(G163) = 0.89), and T242N in TW10 (RRC(N242) = 0.86). 2009 Journal of virology Abstract HIV A146P;A163G;T242N 130;163;201 135;168;206 Capsid 122 128 19109381 Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein. We then asked whether such CTL escape mutations had an impact equivalent to that seen for a benchmark mutation, the M184V antiretroviral drug resistance mutation of reverse transcriptase (RRC(V184) = 0.86). 2009 Journal of virology Abstract HIV M184V 116 121 RT 165 186 19111493 Primary drug resistance in antiretroviral-naive injection drug users. Phenotypic drug resistance was also identified in six (4.7%) patients, four in the RT gene (in patients with mutations K103N, Y181C, M184V and Y188L) and two the protease gene (in two patients with minor PI mutations). 2009 International journal of infectious diseases Abstract HIV K103N;M184V;Y181C;Y188L 119;133;126;143 124;138;131;148 PR;PI;RT 162;204;83 170;206;85 19111493 Primary drug resistance in antiretroviral-naive injection drug users. RESULTS: Genotypic drug resistance was uncommon, and was only identified in six (4.7%) cases, all in the RT gene (L100I, K103N, Y181C, M184V, Y188L, and T215D). 2009 International journal of infectious diseases Abstract HIV K103N;L100I;M184V;T215D;Y181C;Y188L 121;114;135;153;128;142 126;119;140;158;133;147 RT 105 107 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission. 2009 PloS one Abstract HIV Y181C;Y188C;Y188H 68;166;166 73;173;173 HIV infections 49 62 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. The main properties are the binding to: 1- the processing-attachment site at the LTR (long terminal repeat) ends of virus DNA with a K(d) (dissociation constant) in the sub-micromolar range; 2- the whole IN enzyme; and 3- the IN binding domain (IBD) but not the IBD-Asp366Asn variant of LEDGF (lens epidermal derived growth factor) lacking the essential Asp366 residue. 2009 PloS one Abstract HIV D366N;I366N 266;266 275;275 LTR;LTR;Asp;Asp;IN;IN 86;81;266;354;204;226 106;84;269;357;206;228 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. We identified a bi-helix motif (residues 149-186) in the crystal structure of the catalytic core (CC) of the IN-Phe185Lys variant that consists of the alpha(4) and alpha(5) helices connected by a 3 to 5-residue turn. 2009 PloS one Abstract HIV F185K 112 121 IN 109 111 19122141 HIV-1 Tat RNA silencing suppressor activity is conserved across kingdoms and counteracts translational repression of HIV-1. The attenuation in gag mRNA translation is exacerbated by K51A substitution in the Tat double-stranded RNA-binding domain. 2009 Proc Natl Acad Sci U S A Abstract HIV K51A 58 62 Tat;Gag 83;19 86;22 19124665 Treatment with the fusion inhibitor enfuvirtide influences the appearance of mutations in the human immunodeficiency virus type 1 regulatory protein rev. In addition, the presence at week 48 of the E57A(rev) correlates with a significant viremia increase from baseline to week 48 and with a CD4 cell count loss from baseline to week 48. 2009 Antimicrobial agents and chemotherapy Abstract HIV E57A 44 48 Rev 49 52 19124665 Treatment with the fusion inhibitor enfuvirtide influences the appearance of mutations in the human immunodeficiency virus type 1 regulatory protein rev. In particular, a cluster was observed for the Rev mutations E57A (E57A(rev)) and N86S(rev) with the ENF resistance gp41 mutations Q40H (Q40H(gp41)) and L45M(gp41). 2009 Antimicrobial agents and chemotherapy Abstract HIV E57A;E57A;L45M;N86S;Q40H;Q40H 60;66;152;81;130;136 64;71;156;85;134;141 gp41;gp41;gp41;Rev;Rev;Rev 115;141;157;46;71;86 119;145;161;49;74;89 19124665 Treatment with the fusion inhibitor enfuvirtide influences the appearance of mutations in the human immunodeficiency virus type 1 regulatory protein rev. The conformation of this Rev-binding site is disrupted when Q40H(gp41) and L45M(gp41) occur alone while it is restored when both mutations are present. 2009 Antimicrobial agents and chemotherapy Abstract HIV L45M;Q40H 75;60 79;64 gp41;gp41;Rev 65;80;25 69;84;28 19124911 Successful application of laboratory tools for the detection of HIV drug resistance in routine clinical care in Georgia. G190S/A was the most frequent NNRTI mutation (42.2%), followed by K103N (28.9%). 2008 Georgian medical news Abstract HIV G190A;G190S;K103N 0;0;66 7;7;71 NNRTI 30 35 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Altogether, these results account for the predominance of G140S/Q148H mutants in clinical trials using Raltegravir. 2009 Nucleic acids research Abstract HIV G140S;Q148H 58;64 63;69 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. By contrast, the conformational transition converting the inactive form into an active form is rescued by the G140S/Q148H double mutation. 2009 Nucleic acids research Abstract HIV G140S;Q148H 110;116 115;121 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In conclusion, the Q148H mutation is responsible for resistance to Raltegravir whereas the G140S mutation increases viral fitness in the G140S/Q148H context. 2009 Nucleic acids research Abstract HIV G140S;G140S;Q148H;Q148H 91;137;143;19 96;142;148;24 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The Q148H mutation 'freezes' IN into a catalytically inactive state. 2009 Nucleic acids research Abstract HIV Q148H 4 9 IN 29 31 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We found that (i) integration is impaired for Q148H when compared with the wild-type, G140S and G140S/Q148H mutants; and (ii) the N155H and G140S mutations confer lower levels of resistance than the Q148H mutation. 2009 Nucleic acids research Abstract HIV G140S;G140S;G140S;N155H;Q148H;Q148H;Q148H 86;140;96;130;102;46;199 91;145;101;135;107;51;204 19130746 Emergence of antiretroviral drug resistance in therapy-naive HIV infected patients in Hungary. In protease gene only minor resistant mutations were found such as L101 and A71V. 2008 Acta microbiologica et immunologica Hungarica Abstract HIV A71V 76 80 PR 3 11 19130746 Emergence of antiretroviral drug resistance in therapy-naive HIV infected patients in Hungary. Viral variants harbouring resistance mutations such as: M41, T69R, K70R, M184V, T215Y in the pol gene were detected in 14% of the subjects. 2008 Acta microbiologica et immunologica Hungarica Abstract HIV K70R;M184V;T215Y;T69R 67;73;80;61 71;78;85;65 Pol 93 96 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. After treatment, the M184V mutation occurred less frequently among sdNVP-exposed women than among sdNVP-unexposed women, but the frequency of NNRTI-associated mutations was similar between these groups of women with inadequate virologic response. 2009 Clinical infectious diseases Abstract HIV M184V 21 26 NNRTI 142 147 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Drug resistance was assessed using K103N allele-specific real-time polymerase chain reaction assay and population sequencing. 2009 Clinical infectious diseases Abstract HIV K103N 35 40 Pol 67 77 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. However, women with minority K103N mutations before treatment had a reduced durability of virologic suppression. 2009 Clinical infectious diseases Abstract HIV K103N 29 34 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. K103N was detected with the K103N allele-specific real-time polymerase chain reaction assay among sdNVP-exposed and -unexposed women before treatment; detection was strongly predictive of inadequate viral response: 60.9% of women for whom K103N was detected in either viral RNA or DNA did not experience viral suppression or experienced viral rebound, compared with 15.1% of women for whom K103N was not detected (P < .001). 2009 Clinical infectious diseases Abstract HIV K103N;K103N;K103N;K103N 28;239;390;0 33;244;395;5 Pol 60 70 19136678 Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G. Indinavir-associated mutations M46I/L, I84V and V82A/F/T developed earlier in subtype B across the time of exposure to that drug when compared with subtype G counterparts. 2009 The Journal of antimicrobial chemotherapy Abstract HIV I84V;M46I;M46L;V82A;V82F;V82T 39;31;31;48;48;48 43;37;37;56;56;56 19136678 Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G. L90M did not reduce the susceptibility of subtype G to saquinavir, in contrast to subtype B. 2009 The Journal of antimicrobial chemotherapy Abstract HIV L90M 0 4 19136678 Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G. L90M was associated with a lower reduction in the susceptibility of subtype G to nelfinavir when compared with subtype B, and with no reduced susceptibility to saquinavir. 2009 The Journal of antimicrobial chemotherapy Abstract HIV L90M 0 4 19136678 Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G. Likewise, the pattern I54V/L-L90M did not reduce the susceptibility of subtype G to indinavir and saquinavir. 2009 The Journal of antimicrobial chemotherapy Abstract HIV I54L;I54V;L90M 22;22;29 28;28;33 19136678 Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G. RESULTS: Mutation I54V/L was selected by nelfinavir in subtype G isolates, a mutation not previously described for this drug in subtype B. 2009 The Journal of antimicrobial chemotherapy Abstract HIV I54L;I54V 18;18 24;24 19136678 Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G. This was compensated for by the acquisition of M89I in subtype G. 2009 The Journal of antimicrobial chemotherapy Abstract HIV M89I 47 51 19138518 Investigation on the role of the tetrazole in the binding of thiotetrazolylacetanilides with HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. The role of the tetrazole moiety in the binding of aryl thiotetrazolylacetanilides with HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases was explored. 2009 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 108;114 113;119 RT 134 156 19140683 Discovery of chiral cyclopropyl dihydro-alkylthio-benzyl-oxopyrimidine (S-DABO) derivatives as potent HIV-1 reverse transcriptase inhibitors with high activity against clinically relevant mutants. Molecular modeling calculation, enzymatic studies, and surface plasmon resonance experiments allowed us to rationalize the biological behavior of the synthesized compounds, which act as mixed-type inhibitors of HIV-1 RT K103N, with a preferential association to the enzyme-substrate complex. 2009 Journal of medicinal chemistry Abstract HIV K103N 220 225 RT 217 219 19140683 Discovery of chiral cyclopropyl dihydro-alkylthio-benzyl-oxopyrimidine (S-DABO) derivatives as potent HIV-1 reverse transcriptase inhibitors with high activity against clinically relevant mutants. Taken together, our data show that the right combination of stereochemistry on the left and right parts (C6-substituent) of the S-DABO scaffold plays a key role in the inhibition of both wild-type and drug-resistant enzymes, especially the K103N mutant. 2009 Journal of medicinal chemistry Abstract HIV K103N 240 245 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Eight patients had HIV-2 with PI mutations associated with indinavir resistance, including K7R, I54M, V62A, I82F, L90M, L99F; 4 patients had strains with multiple PI resistance-associated mutations. 2009 Clinical infectious diseases Abstract HIV I54M;I82F;K7R;L90M;L99F;V62A 96;108;91;114;120;102 100;112;94;118;124;106 PI;PI 30;163 32;165 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, and T215Y/F) were not observed, with the exception of K70R, which was present together with K65R and Q151M in a strain from 1 patient. 2009 Clinical infectious diseases Abstract HIV D67N;K65R;K70R;K70R;L210W;M41L;Q151M;T215F;T215Y 53;164;59;126;65;47;173;76;76 57;168;63;130;70;51;178;83;83 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The Q151M mutation, which confers multinucleoside resistance in HIV-2, emerged in strains from 9% of patients. 2009 Clinical infectious diseases Abstract HIV Q151M 4 9 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The reverse-transcriptase mutations M184V and K65R, which confer high-level resistance to lamivudine and emtricitabine in HIV-2, were found in strains from 43% and 9% of patients, respectively. 2009 Clinical infectious diseases Abstract HIV K65R;M184V 46;36 50;41 RT 4 25 19147519 Mutations associated with virological response to darunavir/ritonavir in HIV-1-infected protease inhibitor-experienced patients. Cochran-Armitage procedure identified eight mutations with a negative impact on the virological response, namely K14R, K20I, E34Q, I47V, I54M, K55R, T74P and I84V; and two mutations (E35D and V82A) with a positive impact. 2009 The Journal of antimicrobial chemotherapy Abstract HIV E34Q;E35D;I47V;I54M;I84V;K14R;K20I;K55R;T74P;V82A 125;183;131;137;158;113;119;143;149;192 129;188;135;141;162;117;123;147;153;196 19147519 Mutations associated with virological response to darunavir/ritonavir in HIV-1-infected protease inhibitor-experienced patients. CONCLUSIONS: Among the eight mutations with a negative impact on the virological response, I47V, I54M, T74P and I84V were previously described as darunavir resistance-associated mutations. 2009 The Journal of antimicrobial chemotherapy Abstract HIV I47V;I54M;I84V;T74P 91;97;112;103 95;101;116;107 19149765 Analysis and characterization of dimerization inhibition of a multi-drug-resistant human immunodeficiency virus type 1 protease using a novel size-exclusion chromatographic approach. Incubation of PR(MDR) with P27, or other dimerization inhibitors, led to a dose- and time-dependent formation of PR monomers based on the change in elution time by size exclusion and its similar elution time to engineered forms of monomeric PR, namely PR(T26A) and glutathionylated PR. 2009 The Biochemical journal Abstract HIV T26A 255 259 PR;PR;PR;PR;PR 14;113;241;252;282 16;115;243;254;284 19150986 Identifying and characterizing a functional HIV-1 reverse transcriptase-binding site on integrase. An IN K258A substitution that disrupts reverse transcription in infected cells is located at the putative RT-binding surface, and we found that this substitution substantially weakens IN CTD-RT interactions. 2009 The Journal of biological chemistry Abstract HIV K258A 6 11 RT;IN;IN;RT;RT 39;3;184;106;191 60;5;186;108;193 19150986 Identifying and characterizing a functional HIV-1 reverse transcriptase-binding site on integrase. We also identified two additional IN amino acid substitutions located at the putative RT-binding surface (W243E and V250E) that significantly impair viral replication in tissue culture. 2009 The Journal of biological chemistry Abstract HIV V250E;W243E 116;106 121;112 IN;RT 34;86 36;88 19165083 Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. RESULTS: : Resistance to RAL appeared initially associated with selection of single variants (Y143R, Q148R N155H) in the majority of patients; however, in three patients, complex patterns of viral mutations were observed. 2009 AIDS (London, England) Abstract HIV N155H;Q148R;Y143R 107;101;94 112;106;99 19171798 Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection. Thirty randomly chosen antiretroviral drug-naive patients lacking both the K103N and the M184V mutations as determined by conventional sequencing methods were studied, and K103N and M184V viral minority species were found in three (10%) and four (11%) patients, respectively. 2009 Antimicrobial agents and chemotherapy Abstract HIV K103N;K103N;M184V;M184V 75;172;89;182 80;177;94;187 19171798 Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection. We used an allele-specific real-time PCR assay to explore the presence of K103N and M184V minority species among primary human immunodeficiency virus (HIV) infections and their potential influence in HIV transmission. 2009 Antimicrobial agents and chemotherapy Abstract HIV K103N;M184V 74;84 79;89 19173856 [Study on the drug resistance situation among recently infected HIV-1 patients in Dehong]. Minor mutation in PR region such as M361/V, L63P and H69K appeared frequently and the rates were 81.25%, 70.31% and 65.63% respectively. 2008 Zhonghua liu xing bing xue za zhi Abstract HIV H69K;L63P 53;44 57;48 PR 18 20 19176623 Non-cleavage site gag mutations in amprenavir-resistant human immunodeficiency virus type 1 (HIV-1) predispose HIV-1 to rapid acquisition of amprenavir resistance but delay development of resistance to other protease inhibitors. Recombinant HIV-1 clones containing NFV resistance-associated mutations, such as D30N and N88S, had increased susceptibilities to APV, suggesting that antiretroviral regimens including both APV and NFV may bring about favorable antiviral efficacy. 2009 Journal of virology Abstract HIV D30N;N88S 81;90 85;94 19178153 Potent inhibitors of HIV-1 integrase display a two-step, slow-binding inhibition mechanism which is absent in a drug-resistant T66I/M154I mutant. T66I/M154I exhibited little if any time-dependent inhibition by any of the six INIs, as measured by differences in potency upon preincubation or by progress curve analysis. 2009 Biochemistry Abstract HIV M154I;T66I 5;0 10;4 IN 79 83 19182918 Genetic analysis of HIV type 1 strains from newly infected untreated patients in cyprus: high genetic diversity and low prevalence of drug resistance. Additionally, one patient (2.7%) had an L44M amino acid substitution within the HR1 region of gp41 conferring resistance to the enfuvirtide (T20) fusion inhibitor. 2009 AIDS research and human retroviruses Abstract HIV L44M 40 44 gp41 94 98 19182918 Genetic analysis of HIV type 1 strains from newly infected untreated patients in cyprus: high genetic diversity and low prevalence of drug resistance. One patient (2.7%) had an M41L/M and another patient (2.7%) an M184V amino acid substitution in the reverse transcriptase (RT) associated with high-level resistance to RT inhibitors. 2009 AIDS research and human retroviruses Abstract HIV M184V;M41L;M41M 63;26;26 68;32;32 RT;RT;RT 100;123;168 121;125;170 19193782 The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. Furthermore, the replication capacity of HIV-1 containing I132M is severely impaired. 2009 Journal of virology Abstract HIV I132M 58 63 19193782 The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. Subunit-selective mutagenesis studies revealed that the mutation in the p51 subunit of RT was responsible for the increased sensitivity to the drugs, and transient kinetic analyses showed that this hypersusceptibility was due to I132M decreasing the enzyme's affinity for the natural dCTP substrate but increasing its affinity for 3TC-triphosphate. 2009 Journal of virology Abstract HIV I132M 229 234 RT 87 89 19193782 The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. Surprisingly, our data show that I132M confers marked hypersusceptibility to the nucleoside analogs lamivudine (3TC) and tenofovir at both the virus and enzyme levels. 2009 Journal of virology Abstract HIV I132M 33 38 19193782 The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. Taken together, these results help to explain the infrequent selection of I132M in patients for whom NNRTI regimens are failing and furthermore demonstrate that a single mutation outside of the polymerase active site and inside of the p51 subunit of RT can significantly influence nucleotide selectivity. 2009 Journal of virology Abstract HIV I132M 74 79 Pol;NNRTI;RT 194;101;250 204;106;252 19193782 The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. This decrease in viral replication capacity could be partially or completely compensated for by the A62V or L214I mutation, respectively. 2009 Journal of virology Abstract HIV A62V;L214I 100;108 104;113 19193782 The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs. We previously identified a rare mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), I132M, which confers high-level resistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine. 2009 Journal of virology Abstract HIV I132M 116 121 RT;NNRTI;RT;RT 88;195;111;180 109;201;113;182 19195337 Broad advances in understanding HIV resistance to antiretrovirals: report on the XVII International HIV Drug Resistance Workshop. Mechanistic research explored resistance to the integrase inhibitor raltegravir, K65R-mediated resistance to tenofovir and the role of connection domain mutations in resistance to zidovudine. 2008 Antiviral therapy Abstract HIV K65R 81 85 IN 48 57 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Detailed structural analysis shows that three mutants (Q155N, E159D, and W184A) display much more flexible local structures and weaker CA-CA association than the wildtype, primarily due to the loss of interactions (hydrogen bonds, side chain hydrophobic contacts, and pi-stacking) with their neighboring residues. 2009 Biomacromolecules Abstract HIV E159D;Q155N;W184A 62;55;73 67;60;78 Capsid;Capsid;PI 135;138;268 137;140;270 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The simulations show that Q155N and E159D at the major homology region (MHR) and W184A and M185A at the helix 2 region are energetically less favorable than the wild-type, imposing profound negative effects on intermolecular CA-CA dimerization. 2009 Biomacromolecules Abstract HIV E159D;M185A;Q155N;W184A 36;91;26;81 41;96;31;86 Capsid;Capsid 225;228 227;230 19200174 Difference in drug resistance patterns between minor HIV-1 populations in cerebrospinal fluid and plasma. The reverse transcriptase (RT) gene was examined by selective real-time polymerase chain reaction (SPCR), which can detect M184I/V mutants down to 0.2% of the viral population. 2009 HIV medicine Abstract HIV M184I;M184V 123;123 130;130 RT;Pol;RT 4;72;27 25;82;29 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. In a review of integrase inhibitor-naive Australian HIV-1 sequences, primary mutations were not identified, although the accessory mutation G140S was detected. 2009 Retrovirology Abstract HIV G140S 140 145 IN 15 24 19209258 Combating HIV resistance - focus on darunavir. Darunavir resistance-associated mutations have been defined as V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V, and L89V. 2008 Therapeutics and clinical risk management Abstract HIV G73S;I47V;I50V;I54L;I54M;I84V;L33F;L76V;L89V;V11I;V32I 101;81;87;93;93;113;75;107;123;63;69 105;85;91;99;99;117;79;111;127;67;73 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. At low dNTP concentration, K65R RT exhibited lower activity in single-cycle processivity assays while the K65R+M184V mutant showed diminished processivity independent of dNTP concentration. 2009 Retrovirology Abstract HIV K65R;K65R;M184V 27;106;111 31;110;116 RT 32 34 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. ATP-mediated excision of TFV-or ZDV-terminated primer was decreased for K65R and for K65R+M184V RT compared to WT RT. 2009 Retrovirology Abstract HIV K65R;K65R;M184V 72;85;90 76;89;95 RT;RT 96;114 98;116 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. BACKGROUND: We investigated the effects of mutations K65R and K65R plus M184V on enzymatic function and mechanisms of drug resistance in subtype C reverse transcriptase (RT). 2009 Retrovirology Abstract HIV K65R;K65R;M184V 53;62;72 57;66;77 RT;RT 147;170 168;172 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. CONCLUSION: The diminished initiation efficiency of K65R-containing RTs at low dNTP concentrations have been confirmed for subtype C as well as subtype B. 2009 Retrovirology Abstract HIV K65R 52 56 RT 68 71 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Despite decreased excision, this decreased binding/incorporation results in diminished susceptibility of K65R and K65R+M184 RT to TFV-DP. 2009 Retrovirology Abstract HIV K65R;K65R 105;114 109;118 RT 124 126 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. K65R and K65R+M184V displayed 9.8-and 5-fold increases in IC50 for TFV-DP compared to WT RT. 2009 Retrovirology Abstract HIV K65R;M184V;K65R 9;14;0 13;19;4 RT 89 91 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. METHODS: Recombinant subtype C HIV-1 RTs containing K65R or K65R+M184V were purified from Escherichia coli. 2009 Retrovirology Abstract HIV K65R;K65R;M184V 52;60;65 56;64;70 RT 37 40 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. RESULTS: The efficiency of tRNA-primed (-)ssDNA synthesis by subtype C RTs was: WT > K65R > K65R+M184V RT. 2009 Retrovirology Abstract HIV K65R;K65R;M184V 85;92;97 89;96;102 RT;RT 71;103 74;105 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The Ki/Km of TFV was increased by 4.1-and 7.2-fold, respectively, for K65R and K65R+M184V compared to WT RT. 2009 Retrovirology Abstract HIV K65R;K65R;M184V 70;79;84 74;83;89 RT 105 107 19219276 Prevalence of resistance-associated mutations in human immunodeficiency virus type 1-positive individuals failing HAART in Rio de Janeiro, Brazil. The most prevalent resistance mutations were: M184V (60.7%), T215Y (49.6%) and M41L (46.7%) in the RT gene and L90M (19.6%), M46I (16.2%) and D30N (12.8%) in the PR gene. 2008 The Brazilian journal of infectious diseases Abstract HIV D30N;L90M;M184V;M41L;M46I;T215Y 142;111;46;79;125;61 146;115;51;83;129;66 PR;RT 162;99 164;101 19219633 Drug-resistant molecular mechanism of CRF01_AE HIV-1 protease due to V82F mutation. In this work, we have performed computer simulation of subtype AE HIV-1 PR with the drugs lopinavir (LPV) and nelfinavir (NFV), and examined the mechanism of resistance of the V82F mutation of this protease against LPV both structurally and energetically. 2009 Journal of computer-aided molecular design Abstract HIV V82F 176 180 PR;PR 198;72 206;74 19219633 Drug-resistant molecular mechanism of CRF01_AE HIV-1 protease due to V82F mutation. The V82F mutation at the active site results in a conformational change of 79's loop region and displacement of LPV from its proper binding site, and these changes lead to rotation of the side-chains of residues D25 and I50'. 2009 Journal of computer-aided molecular design Abstract HIV V82F 4 8 19221102 Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. In most patients, raltegravir failure is associated with mutations in the IN gene, through two different genetic pathways: 155 (N155H) or 148 (Q148K/R/H). 2009 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148K;Q148R 128;143;143;143 133;152;152;152 IN 74 76 19221102 Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. In the two patients switching from the 155 to the 148 pathway, clonal analysis showed that Q148R/H and N155H mutations were present on different strands, suggesting that these two pathways are independent. 2009 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148R 103;91;91 108;98;98 19221102 Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. We observed a greater variability among quasispecies associated with the 155 pathway, and IC(50) determinations showed that the fold resistance to raltegravir, relative to wild-type, was 10 for the N155H mutant and 50 for the G140S+Q148H mutant. 2009 The Journal of antimicrobial chemotherapy Abstract HIV G140S;N155H;Q148H 226;198;232 231;203;237 19223637 Apricitabine does not select additional drug resistance mutations in tissue culture in human immunodeficiency virus type 1 variants containing K65R, M184V, or M184V plus thymidine analogue mutations. Human immunodeficiency virus type 1 containing the reverse transcriptase mutation M184V or K65R or mutations M41L, M184V, and T215Y did not accumulate additional resistance mutations in the reverse transcriptase when increasing amounts of apricitabine drug pressure were applied. 2009 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V;M184V;M41L;T215Y 91;82;115;109;126 95;87;120;113;131 RT;RT 51;190 72;211 19223644 Human immunodeficiency virus type 1 isolates with the reverse transcriptase (RT) mutation Q145M retain nucleoside and nonnucleoside RT inhibitor susceptibility. Q145M should not, therefore, be considered an RT inhibitor resistance mutation. 2009 Antimicrobial agents and chemotherapy Abstract HIV Q145M 0 5 RT 46 48 19223644 Human immunodeficiency virus type 1 isolates with the reverse transcriptase (RT) mutation Q145M retain nucleoside and nonnucleoside RT inhibitor susceptibility. Q145M, a mutation in a conserved human immunodeficiency virus type 1 reverse transcriptase (RT) region, was reported to decrease susceptibility to multiple RT inhibitors. 2009 Antimicrobial agents and chemotherapy Abstract HIV Q145M 0 5 RT;RT;RT 69;92;156 90;94;158 19223644 Human immunodeficiency virus type 1 isolates with the reverse transcriptase (RT) mutation Q145M retain nucleoside and nonnucleoside RT inhibitor susceptibility. We report that Q145M and other Q145 mutations do not emerge with RT inhibitors nor decrease RT inhibitor susceptibility. 2009 Antimicrobial agents and chemotherapy Abstract HIV Q145M 15 20 RT;RT 65;92 67;94 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. DeltaQ50-m4-CVN and S52P-m4-CVN bind gp120 at low-nanomolar concentrations and recover in part the antiviral activity of wt CV-N. 2009 Biopolymers Abstract HIV S52P 20 24 gp120 37 42 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Here, we present two mutants, DeltaQ50-m4-CVN and S52P-m4-CVN, which fold exclusively as domain-swapped dimers while containing the four mutations that abolish domain A. 2009 Biopolymers Abstract HIV S52P 50 54 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. To clarify the role of multiple-binding sites in CV-N, we previously designed a monomeric mutant, P51G-m4-CVN, in which the binding site on domain A was rendered ineffective by four mutations (m4); in addition, a hinge region mutation (P51G) hinders the formation of a domain swapped dimer. 2009 Biopolymers Abstract HIV P51G;P51G 98;236 102;240 19235860 Prediction of the virological response to etravirine in clinical practice: Comparison of three genotype algorithms. Most of the discordance was due to the differential weights attributed to Y181C/V, L100I, and K101P in the two weighted algorithms. 2009 Journal of medical virology Abstract HIV K101P;L100I;Y181C;Y181V 94;83;74;74 99;88;81;81 19239356 Profile of HIV type 1 infection and genotypic resistance mutations to antiretroviral drugs in treatment-naive HIV type 1-infected individuals in Hai Phong, Viet Nam. We found protease inhibitor-associated major resistance mutations in one of the 294 cases analyzed (0.3%; mutation M46I). 2009 AIDS research and human retroviruses Abstract HIV M46I 115 119 PR 9 17 19239356 Profile of HIV type 1 infection and genotypic resistance mutations to antiretroviral drugs in treatment-naive HIV type 1-infected individuals in Hai Phong, Viet Nam. We found RT inhibitor-associated major resistance mutations in 7/273 cases (2.6%; one occurrence each of L74I, M184I, and K219E; three cases of K103N; and two cases of G190E). 2009 AIDS research and human retroviruses Abstract HIV G190E;K103N;K219E;L74I;M184I 168;144;122;105;111 173;149;127;109;116 RT 9 11 19239358 Enfuvirtide (T-20) resistance-related mutations in HIV type 1 subtypes B, C, and F isolates from Brazilian patients failing HAART. Amino acid changes in codons G36D/S, I37V, V38A/M/E, Q39H/R, Q40H, N42T, and N43D can confer resistance to EFV. 2009 AIDS research and human retroviruses Abstract HIV G36D;G36S;I37V;N42T;N43D;Q39H;Q39R;Q40H;V38A;V38E;V38M 29;29;37;67;77;53;53;61;43;43;43 35;35;41;71;81;59;59;65;51;51;51 19239358 Enfuvirtide (T-20) resistance-related mutations in HIV type 1 subtypes B, C, and F isolates from Brazilian patients failing HAART. In contrast, when 1079 sequences from drug-naive patients were analyzed, only one showed the G36D substitution. 2009 AIDS research and human retroviruses Abstract HIV G36D 93 97 19239358 Enfuvirtide (T-20) resistance-related mutations in HIV type 1 subtypes B, C, and F isolates from Brazilian patients failing HAART. This finding indicates a strong association between the selected position G36D and HAART therapy (p < 0.0001). 2009 AIDS research and human retroviruses Abstract HIV G36D 74 78 19239358 Enfuvirtide (T-20) resistance-related mutations in HIV type 1 subtypes B, C, and F isolates from Brazilian patients failing HAART. We found a high prevalence (7.6%) of EFV-associated mutation G36D in this cohort of patients failing HAART therapy, five isolates from subtype B (11.11% within this group). 2009 AIDS research and human retroviruses Abstract HIV G36D 61 65 19244337 Suppression of Tetherin-restricting activity upon human immunodeficiency virus type 1 particle release correlates with localization of Vpu in the trans-Golgi network. Interestingly, clathrin light chain small interfering RNA-directed disruption of Vpu trafficking from the TGN to the endosomal system slightly stimulated Vpu-mediated HIV-1 release and completely restored the activity of the Vpu R30A,K31A mutant. 2009 Journal of virology Abstract HIV K31A;R30A 234;229 238;235 Vpu;Vpu;Vpu 81;154;225 84;157;228 19262402 Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil. Major mutations associated with elvitegravir or raltegravir in vivo resistance (Q148K/H/R, N155H) were not detected. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N155H;Q148H;Q148K;Q148R 91;80;80;80 96;89;89;89 19262402 Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil. V72I and V201I were considered as polymorphisms. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V201I;V72I 9;0 14;4 19275497 Etravirine, a next-generation nonnucleoside reverse-transcriptase inhibitor. In vitro resistance and treatment failure is associated with the development of multiple NNRTI resistance mutations other than the K103N mutation. 2009 Clinical infectious diseases Abstract HIV K103N 131 136 NNRTI 89 94 19276764 Association of mitochondrial allele 4216C with increased risk for complicated sepsis and death after traumatic injury. Clinical data were collected prospectively and T4216C was genotyped by polymerase chain reaction-restriction fragment length polymorphism. 2009 The Journal of trauma Abstract HIV T4216C 47 53 Pol 71 81 19276764 Association of mitochondrial allele 4216C with increased risk for complicated sepsis and death after traumatic injury. These DNA variants include a nonsynonymous polymorphism (T4216C) in the NADH dehydrogenase 1 gene (ND1), which encodes a key member of Complex I of the electron transport chain. 2009 The Journal of trauma Abstract HIV T4216C 57 63 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. 2009 AIDS (London, England) Abstract HIV F53L;I47V;K219R;M41L;N88D 297;291;226;212;303 301;295;231;216;307 NNRTI;NRTI;PR;NNRTI;NRTI 319;130;248;366;174 354;162;256;371;178 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Phylogenetic analyses have suggested common ancestry between the mother's virus strain carrying K101E with the viral sequences from the child. 2009 PloS one Abstract HIV K101E 96 101 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The analysis showed that the child received a minor NNRTI resistant variant, containing the mutation K101E that was present in less than 1% of the mother's quasispecies. 2009 PloS one Abstract HIV K101E 101 106 NNRTI 52 57 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The child's first genotype demonstrated a minor non-nucleoside reverse transcriptase inhibitor (K101E), and during her treatment with reverse transcriptase and protease inhibitors full resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) emerged (G190A). 2009 PloS one Abstract HIV G190A;K101E 264;96 269;101 NNRTI;NNRTI;RT;PR;NNRTI 48;199;134;160;248 84;235;155;168;253 19279098 Selection of a simian-human immunodeficiency virus strain resistant to a vaginal microbicide in macaques. Dual-virus competitions revealed a dramatic increase in fitness of chimeric virus containing env(m584) (K315R/N640D) over that containing env(p3), but again, only in rhesus CCR5-expressing cells. 2009 Journal of virology Abstract HIV K315R;N640D 104;110 109;115 Env;Env 93;138 96;141 19279098 Selection of a simian-human immunodeficiency virus strain resistant to a vaginal microbicide in macaques. Two specific mutations located in the V3 region of gp120 (K315R) and C-helical domain of gp41 (N640D) were identified in a macaque (m584) pretreated with a 100 microM dose of PSC-RANTES. 2009 Journal of virology Abstract HIV K315R;N640D 58;95 63;100 gp120;gp41 51;89 56;93 19279107 Impact of human immunodeficiency virus type 1 resistance to protease inhibitors on evolution of resistance to the maturation inhibitor bevirimat (PA-457). Significantly, the emergence of BVM resistance was delayed in the context of the PIR PR, and the SP1-A1V mutation was acquired most frequently with either WT or PIR PR. 2009 Journal of virology Abstract HIV A1V 101 104 SP1;PR;PR 97;85;165 100;87;167 19279107 Impact of human immunodeficiency virus type 1 resistance to protease inhibitors on evolution of resistance to the maturation inhibitor bevirimat (PA-457). The BVM-resistant mutant SP1-A1V was an exception, as it supported robust replication in the context of either wild-type (WT) or PIR PR, even at high BVM concentrations. 2009 Journal of virology Abstract HIV A1V 29 32 SP1;PR 25;133 28;135 19279107 Impact of human immunodeficiency virus type 1 resistance to protease inhibitors on evolution of resistance to the maturation inhibitor bevirimat (PA-457). We predict that the SP1-A1V substitution is the most likely to emerge in vivo, as this mutant replicates robustly independently of PR mutations or BVM. 2009 Journal of virology Abstract HIV A1V 24 27 SP1;PR 20;131 23;133 19279440 Highly restricted T-cell receptor repertoire in the CD8+ T-cell response against an HIV-1 epitope with a stereotypic amino acid substitution. METHODS: PBMCs from HLA-A*2402(A24)-positive patients were stimulated with peptides representing a wild-type CTL epitope in the HIV-1 Nef protein [Nef138-10(wt)] or an escape mutant with a Y to F (Y139F) substitution at the second position [Nef138-10(2F)]. 2009 AIDS (London, England) Abstract HIV Y139F 197 202 Nef;Nef;Nef 134;147;241 137;150;244 19281225 Indolylarylsulfones bearing natural and unnatural amino acids. Discovery of potent inhibitors of HIV-1 non-nucleoside wild type and resistant mutant strains reverse transcriptase and coxsackie B4 virus. Against the mutant L100I, K103N, and Y181C RT HIV-1 strains in CEM cells, sulfones 3, 4, 19, 27, and 31 were comparable to EFV. 2009 Journal of medicinal chemistry Abstract HIV K103N;L100I;Y181C 26;19;37 31;24;42 RT 43 45 19281225 Indolylarylsulfones bearing natural and unnatural amino acids. Discovery of potent inhibitors of HIV-1 non-nucleoside wild type and resistant mutant strains reverse transcriptase and coxsackie B4 virus. The binding mode of 19 was not affected by the L100I mutation and was consistent with the interactions reported for the WT strain. 2009 Journal of medicinal chemistry Abstract HIV L100I 47 52 19282784 HIV-1 transmission cluster with T215D revertant mutation among newly diagnosed patients from the Basque Country, Spain. One of these comprised 14 individuals, 12 of them MSM, with the T215D revertan mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV T215D 64 69 19287298 Women exposed to single-dose nevirapine in successive pregnancies: effectiveness and nonnucleoside reverse transcriptase inhibitor resistance. Sensitive mutation-specific real-time PCR testing found three of 12 previously exposed women who transmitted HIV-1 to their infants had either K103N or Y181C at baseline compared with one of eight ARV-naive, transmitting women who had Y181C. 2009 AIDS (London, England) Abstract HIV K103N;Y181C;Y181C 143;152;235 148;157;240 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. RESULTS: Four positively-selected residues were significantly associated with HLA class I alleles, including HLA B*1302 (K4R, P = 0.0008 and I5L, P = 0.0108), A*7401 (S9N, P = 0.0002) and A*30 genotypes (P7S, P = 0.009), suggesting epitopes restricted by these alleles are present in this region. 2009 AIDS (London, England) Abstract HIV I5L;K4R;P7S;S9N 141;121;204;167 144;124;207;170 19289522 Antiviral activity of MK-4965, a novel nonnucleoside reverse transcriptase inhibitor. MK-4965 is also highly potent against the WT virus and two most prevalent NNRTI-resistant viruses (viruses that harbor the K103N or the Y181C mutation), against which it had 95% effective concentrations (EC(95)s) of <30 nM in the presence of 10% fetal bovine serum. 2009 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 123;136 128;141 NNRTI 74 79 19289522 Antiviral activity of MK-4965, a novel nonnucleoside reverse transcriptase inhibitor. The compound displays potency at subnanomolar concentrations against wild-type (WT), K103N, and Y181C reverse transcriptase (RT) in biochemical assays. 2009 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 85;96 90;101 RT;RT 102;125 123;127 19290031 Characterization and structural analysis of HIV-1 integrase conservation. All primary signature mutations emerging in patients failing raltegravir (Y143R, Q148H/K/R, N155H) or elvitegravir (T66I, E92Q, S147G, Q148H/K/R, N155H), as well as secondary mutations (H51Y, T66A/K, E138K, G140S/A/C, Y143C/H, K160N, R166S, E170A, S230R, D232N, R263K) were completely absent or highly infrequent (< 0.5%) in integrase inhibitor-naive patients, either infected with HIV-1 B subtype (drug-naive or antiretroviral-treated), or non-B subtypes/group N and O. 2009 AIDS reviews Abstract HIV D232N;E138K;E170A;E92Q;G140A;G140C;G140S;H51Y;K160N;N155H;N155H;Q148H;Q148H;Q148K;Q148K;Q148R;Q148R;R166S;R263K;S147G;S230R;T66A;T66I;T66K;Y143C;Y143H;Y143R 255;200;241;122;207;207;207;186;227;92;146;81;135;81;135;81;135;234;262;128;248;192;116;192;218;218;74 260;205;246;126;216;216;216;190;232;97;151;90;144;90;144;90;144;239;267;133;253;198;120;198;225;225;79 IN 325 334 19290031 Characterization and structural analysis of HIV-1 integrase conservation. Differently, other mutations (L74M, T97A, S119G/R, V151I, K156N, E157Q, G163K/R, V165I, I203M, T206S, S230N) occurred as natural polymorphisms with a different prevalence according to different HIV-1 subtype/circulating recombinant form/group. 2009 AIDS reviews Abstract HIV E157Q;G163K;G163R;I203M;K156N;L74M;S119G;S119R;S230N;T206S;T97A;V151I;V165I 65;72;72;88;58;30;42;42;102;95;36;51;81 70;79;79;93;63;34;49;49;107;100;40;56;86 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. By contrast, reverting the A431V or I437V mutation in these highly evolved sequences had little effect on RC. 2009 PLoS pathogens Abstract HIV A431V;I437V 27;36 32;41 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Further compensatory mutations render viral RC independent of the A431V or I437V mutations while their effect on resistance persists. 2009 PLoS pathogens Abstract HIV A431V;I437V 66;75 71;80 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. The effect of Gag on resistance depended on the presence of cleavage site mutations A431V or I437V in NC-SP2-p6 and correlated with processing of the NC/SP2 cleavage site. 2009 PLoS pathogens Abstract HIV A431V;I437V 84;93 89;98 Gag;NC;NC;Gag;SP2;SP2 14;102;150;109;105;153 17;104;152;111;108;156 1930105 Biochemical and genetical analysis of AZT-resistant HIV-mutants. the Lys 70----Arg and the Thr 215----Tyr transitions. 1991 Behring Institute Mitteilungen Abstract HIV K70R;T215Y 4;26 17;40 19320243 Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors. These included V90I, A98G, L100I, K1O1E/P/Q, K103H/N/S/T, V106A/I/M, V108I, E138G/K/Q, V179D/E/F/G/I, Y181C/I/V, Y188C/H/L, V189I, G190A/C/E/Q/S, H221Y, P225H, F227C/L, M230I/L, P236L, K238N/T and Y318F. 2009 Antiviral therapy Abstract HIV A98G;E138G;E138K;E138Q;F227C;F227L;G190A;G190C;G190E;G190Q;G190S;H221Y;K103H;K103N;K103S;K103T;K238N;K238T;L100I;M230I;M230L;P225H;P236L;V106A;V106I;V106M;V108I;V179D;V179E;V179F;V179G;V179I;V189I;V90I;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L;Y318F 21;76;76;76;160;160;131;131;131;131;131;146;45;45;45;45;185;185;27;169;169;153;178;58;58;58;69;87;87;87;87;87;124;15;102;102;102;113;113;113;197 25;85;85;85;167;167;144;144;144;144;144;151;56;56;56;56;192;192;32;176;176;158;183;67;67;67;74;100;100;100;100;100;129;19;111;111;111;122;122;122;202 19320246 Genetic barriers for integrase inhibitor drug resistance in HIV type-1 B and CRF02_AG subtypes. CONCLUSIONS: The major IN mutations E92Q, Q148K/R/H, N155H and E157Q (implicated in the resistance of IN inhibitors RAL and EVG) are highly conserved between subtypes B and CRF02_AG and display a similar genetic barrier. 2009 Antiviral therapy Abstract HIV E157Q;E92Q;N155H;Q148H;Q148K;Q148R 63;36;53;42;42;42 68;40;58;51;51;51 IN;IN 23;102 25;104 19320246 Genetic barriers for integrase inhibitor drug resistance in HIV type-1 B and CRF02_AG subtypes. Nevertheless, at positions 140 and 151, the variability between subtypes affected the genetic barrier for the mutations G140C, G140S and V1511 with a higher genetic barrier being calculated for subtype CRF02_AG. 2009 Antiviral therapy Abstract HIV G140C;G140S 120;127 125;132 19323038 HIV-1 drug resistance mutations in children who failed non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Thymidine analoque mutations, M184V/I, and Q151M were observed in 38%, 33%, and 5%. 2009 The Southeast Asian journal of tropical medicine and public health Abstract HIV M184I;M184V;Q151M 30;30;43 37;37;48 19323590 Darunavir: a review of its use in the management of HIV infection in adults. In a 24-week analysis of pooled data from the POWER 1 and 2 studies in treatment-experienced patients, 11 protease mutations associated with a reduced response to boosted darunavir were identified (V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V and L89V). 2009 Drugs Abstract HIV G73S;I47V;I50V;I54L;I54M;I84V;L33F;L76V;L89V;V11I;V32I 236;216;222;228;228;248;210;242;257;198;204 240;220;226;234;234;252;214;246;261;202;208 PR 106 114 19327053 Analysis of pol integrase sequences in diverse HIV type 1 strains using a prototype genotyping assay. Some samples had other mutations selected by these drugs including T97A, and some had amino acid polymorphisms at positions associated with raltegravir and elvitegravir resistance. 2009 AIDS research and human retroviruses Abstract HIV T97A 67 71 19327053 Analysis of pol integrase sequences in diverse HIV type 1 strains using a prototype genotyping assay. Two samples had E92Q (both subtype B) and eight had E157Q (2A, 1C, 1D, 1F, 3 CRF02_AG). 2009 AIDS research and human retroviruses Abstract HIV E157Q;E92Q 52;16 57;20 19336453 Virological and immunological response in HIV-1-infected patients with multiple treatment failures receiving raltegravir and optimized background therapy, ANRS CO3 Aquitaine Cohort. Raltegravir-related mutations emerged in 9 of 11 failing patients (82%): Q148H/R (n = 5), N155S/H (n = 3) and S230N (n = 1). 2009 The Journal of antimicrobial chemotherapy Abstract HIV N155H;N155S;Q148H;Q148R;S230N 90;90;73;73;110 97;97;80;80;115 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. RESULTS: Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. 2009 The Journal of infectious diseases Abstract HIV G190A;K103N 161;151 166;157 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. 2009 The Journal of infectious diseases Abstract HIV K65R;K65R;M184V;M184V;Q151M;Q151M 115;237;123;254;95;243 119;241;128;259;100;248 NRTI 280 284 19363451 Molecular epidemiology of HIV-1 in St Petersburg, Russia: predominance of subtype A, former Soviet Union variant, and identification of intrasubtype subclusters. A second subcluster (17.4% AFSU viruses) corresponds to the variant with the V77I substitution in protease, which is widely circulating in different FSU countries. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V77I 77 81 PR 98 106 19372871 Viral fitness: relation to drug resistance mutations and mechanisms involved: nucleoside reverse transcriptase inhibitor mutations. Further studies have helped explain the antagonistic effects between amino acid substitutions, K65R, L74V, M184V, and thymidine analogue mutations, showing how viral replicative fitness influences the evolution of thymidine analogue resistance pathways. 2007 Current opinion in HIV and AIDS Abstract HIV K65R;L74V;M184V 95;101;107 99;105;112 19372874 Mechanisms of resistance associated with excision of incorporated nucleotide analogue inhibitors of HIV-1 reverse transcriptase. M184V, L74V, and K65R that diminish the effects of thymidine analogue-associated mutations. 2007 Current opinion in HIV and AIDS Abstract HIV K65R;L74V;M184V 17;7;0 21;11;5 19372874 Mechanisms of resistance associated with excision of incorporated nucleotide analogue inhibitors of HIV-1 reverse transcriptase. SUMMARY: The non-thymidine analogue-associated mutations M184V, L74V, and K65R show incompatibilities with thymidine-analogue-associated mutations. 2007 Current opinion in HIV and AIDS Abstract HIV K65R;L74V;M184V 74;64;57 78;68;62 19374129 Comparative studies on inhibitors of HIV protease: a target for drug design. The HIV protease-nelfinavir complex (PDB code: 1OHR) and HIV protease V82F/I84V double mutant-tipranavir complex (PDB code: 1D4S) were used as templates for introducing mutations on the HIV protease active site. 2008 In silico biology Abstract HIV I84V;V82F 75;70 79;74 PR;PR;PR 8;61;190 16;69;198 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Three of the compounds show low-micromolar antiviral activity toward either or both the wild-type and Y181C HIV-1 strains. 2009 Journal of chemical information and modeling Abstract HIV Y181C 102 107 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. To discover non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) that are effective against both wild-type (WT) virus and variants that encode the clinically troublesome Tyr181Cys (Y181C) RT mutation, virtual screening by docking was carried out using three RT structures and more than 2 million commercially available compounds. 2009 Journal of chemical information and modeling Abstract HIV Y181C;Y181C 183;194 192;199 RT;NNRTI;RT;RT 47;70;201;271 68;76;203;273 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Two of the structures are for WT-virus with different conformations of Tyr181, while the third structure incorporates the Y181C modification. 2009 Journal of chemical information and modeling Abstract HIV Y181C 122 127 19375978 Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure. CONCLUSIONS: K103N minorities were found in 20.1% of the patients, whereas the prevalence of major K103N populations was 3% in the total RESINA-cohort. 2009 Journal of clinical virology Abstract HIV K103N;K103N 13;99 18;104 19375978 Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure. K103N minorities were found in 20.1% of the samples, more frequently in HIV-1 non-B subtypes (40.6%) than in subtype B (15.0%) (p=0.0025). 2009 Journal of clinical virology Abstract HIV K103N 0 5 19375978 Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure. K103N minorities were more frequent in non-B subtypes. 2009 Journal of clinical virology Abstract HIV K103N 0 5 19375978 Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure. RESULTS: Bulk-sequencing detected 1 NNRTI mutation (no K103N) in six patients (1.26%). 2009 Journal of clinical virology Abstract HIV K103N 55 60 NNRTI 36 41 19375978 Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure. The relative amount of RT-K103N was measured by primer specific PCR. 2009 Journal of clinical virology Abstract HIV K103N 26 31 RT 23 25 19375978 Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure. There is some evidence for a higher risk of NNRTI-treatment failure in patients with K103N minorities; however, the majority of patients with minority underwent a successful first-line-treatment. 2009 Journal of clinical virology Abstract HIV K103N 85 90 NNRTI 44 49 19382173 Study on the inhibitory mechanism and binding mode of the hydroxycoumarin compound NSC158393 to HIV-1 integrase by molecular modeling. In this work, the binding modes of the wild type IN core domain and the two mutants, that is, W132G and C130S, with the 4-hydroxycoumarin compound NSC158393 were evaluated by using the "relaxed complex" molecular docking approach combined with molecular dynamics (MD) simulations. 2009 Biopolymers Abstract HIV C130S;W132G 104;94 109;99 IN 49 51 19382254 Absence of genotypic drug resistance and presence of several naturally occurring polymorphisms of human immunodeficiency virus-1 CRF06_cpx in treatment-naive patients in Estonia. The most common polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%, 99%, and 100%, respectively. 2009 Journal of medical virology Abstract HIV H69K;K14R;L89M;M36I 64;52;74;58 68;56;78;62 PR 37 39 19382262 Association of IL-4 589 C/T promoter and IL-4RalphaI50V receptor polymorphism with susceptibility to HIV-1 infection in North Indians. Homozygous IL-4Ralpha I50I genotype was significantly increased in HSP group compared with HSN (58.88% vs. 2009 Journal of medical virology Abstract HIV I50I 22 26 19382262 Association of IL-4 589 C/T promoter and IL-4RalphaI50V receptor polymorphism with susceptibility to HIV-1 infection in North Indians. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 promoter 589 C/T and IL-4 Ralpha I50V affect the susceptibility to HIV infection and its progression to AIDS in North Indian individuals. 2009 Journal of medical virology Abstract HIV I50V 124 128 AIDS;HIV infections 195;158 199;171 19382262 Association of IL-4 589 C/T promoter and IL-4RalphaI50V receptor polymorphism with susceptibility to HIV-1 infection in North Indians. The subjects were genotyped for IL-4 589 C/T promoter polymorphism and IL-4 Ralpha I50V by polymerase chain reaction restriction fragment length polymorphism. 2009 Journal of medical virology Abstract HIV I50V 83 87 Pol 91 101 19388823 Low prevalence of drug resistance transmitted virus in HIV Type 1-infected ARV-naive patients in Cambodia. RT analysis indicated that only 1 patient out of 67, presenting K103N and M184V mutations, was resistant to NVP/EFV and 3TC/FTC. 2009 AIDS research and human retroviruses Abstract HIV K103N;M184V 64;74 69;79 RT 0 2 19391634 Proteochemometric modeling of drug resistance over the mutational space for multiple HIV protease variants and multiple protease inhibitors. The model revealed the most deleterious mutations in the protease to be D30N, V32I, G48V, I50V, I54V, V82A, I84V, and L90M. 2009 Journal of chemical information and modeling Abstract HIV D30N;G48V;I50V;I54V;I84V;L90M;V32I;V82A 72;84;90;96;108;118;78;102 76;88;94;100;112;122;82;106 PR 57 65 19400735 Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India. All the study sequences harbored N42S, a natural polymorphism associated with increased susceptibility to ENF. 2009 AIDS research and human retroviruses Abstract HIV N42S 33 37 19400735 Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India. In subtype B-infected individuals, the various HR1 region substitutions in env gp41 that have been associated with ENF resistance include A30V, L33S/T/V, L34M, G36D/E/S/V, I37T/K/V, V38A/M/E/G, Q39R, Q40H, N42T/D, N43D/K/S, L44M, L45M, R46M, L54M, and Q56K/R as well as N126K and S138A in the HR2 region. 2009 AIDS research and human retroviruses Abstract HIV A30V;G36D;G36E;G36S;G36V;I37K;I37T;I37V;L33S;L33T;L33V;L34M;L44M;L45M;L54M;N126K;N42D;N42T;N43D;N43K;N43S;Q39R;Q40H;Q56K;Q56R;R46M;S138A;V38A;V38E;V38G;V38M 138;160;160;160;160;172;172;172;144;144;144;154;224;230;242;270;206;206;214;214;214;194;200;252;252;236;280;182;182;182;182 142;170;170;170;170;180;180;180;152;152;152;158;228;234;246;275;212;212;222;222;222;198;204;258;258;240;285;192;192;192;192 gp41;Env 79;75 83;78 19400735 Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India. Of the mutations V38A and N140I, known to provide immunologic gain, the latter was observed in four subtype C sequences. 2009 AIDS research and human retroviruses Abstract HIV N140I;V38A 26;17 31;21 19400735 Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India. Q56K was observed in a subtype A1 sequence. 2009 AIDS research and human retroviruses Abstract HIV Q56K 0 4 19400735 Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India. The mutation L54M was seen in seven subtype C and two CRF_AE study sequences. 2009 AIDS research and human retroviruses Abstract HIV L54M 13 17 19400735 Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India. The presence of L54M and Q56K in combination is associated with 5-fold reduced sensitivity to inhibition by ENF. 2009 AIDS research and human retroviruses Abstract HIV L54M;Q56K 16;25 20;29 19400736 Structural basis of drug resistance by genetic variants of HIV type 1 clade c protease from India. The E35D mutation affects the flap structure in clade B strains and E35N and E35K mutation, seen in our modeled strains, have a more profound effect. 2009 AIDS research and human retroviruses Abstract HIV E35D;E35K;E35N 4;77;68 8;81;72 19403922 Screening for NNRTIs with slow dissociation and high affinity for a panel of HIV-1 RT variants. A lead optimization library consisting of 800 HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) was screened in parallel against 4 clinically relevant variants of HIV-1 RT (Wt, L100I, Y181C, and K103N) using a surface plasmon resonance-based biosensor. 2009 Journal of biomolecular screening Abstract HIV K103N;L100I;Y181C 207;189;196 212;194;201 NNRTI;NNRTI;RT 52;100;181 87;106;183 19414275 Bridge water mediates nevirapine binding to wild type and Y181C HIV-1 reverse transcriptase--evidence from molecular dynamics simulations and MM-PBSA calculations. Binding free energies and thermodynamic property differences for nevirapine bound to wild type and Y181C HIV-1 reverse transcriptase were investigated, and the results were compared with available experimental data. 2009 Journal of molecular graphics & modelling Abstract HIV Y181C 99 104 RT 111 132 19414275 Bridge water mediates nevirapine binding to wild type and Y181C HIV-1 reverse transcriptase--evidence from molecular dynamics simulations and MM-PBSA calculations. Including this bridge water in the MM-PBSA calculations reoriented the binding energies from -32.20 to -37.65 kcal/mol and -28.07 to -29.82 kcal/mol in the wild type and Y181C HIV-1 RT, respectively. 2009 Journal of molecular graphics & modelling Abstract HIV Y181C 170 175 RT 182 184 19414275 Bridge water mediates nevirapine binding to wild type and Y181C HIV-1 reverse transcriptase--evidence from molecular dynamics simulations and MM-PBSA calculations. Moreover, the dynamics of Val179, Tyr181Cys, Gly190 and Leu234 in the binding pocket showed additional attractive energetic contributions in helping nevirapine binding. 2009 Journal of molecular graphics & modelling Abstract HIV Y181C 34 43 19414275 Bridge water mediates nevirapine binding to wild type and Y181C HIV-1 reverse transcriptase--evidence from molecular dynamics simulations and MM-PBSA calculations. We found that the bridge water is the key in stabilizing the bound complex; however, in the Y181C RT complex this bridge water showed weaker hydrogen bond formation, lack of attractive force to nevirapine and lack of binding efficiency, leading to the failure of nevirapine against the Y181C HIV-1 RT. 2009 Journal of molecular graphics & modelling Abstract HIV Y181C;Y181C 92;286 97;291 RT;RT 98;298 100;300 19415671 Synthesis and studies of new 2-(coumarin-4-yloxy)-4,6-(substituted)-S-triazine derivatives as potential anti-HIV agents. e., diaryltriazine (DATA) are reported as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus HIV-1 (III-B), HIV-2 (ROD), and the double RT mutant HIV-1 (K103N and Y181C) were assessed. 2009 Archiv der Pharmazie Abstract HIV K103N;Y181C 241;251 247;256 NNRTI;NNRTI;RT 48;97;224 84;103;226 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/microl (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18). 2009 AIDS (London, England) Abstract HIV K65R;K70E 17;26 21;30 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Ninety-three percent of samples had nonnucleoside reverse transcriptase inhibitor mutations, and 81% had the M184V mutation. 2009 AIDS (London, England) Abstract HIV M184V 109 114 NNRTI 36 71 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. The most frequent pattern included M184V and nonnucleoside reverse transcriptase inhibitor mutations along with at least one thymidine analog mutation (56%). 2009 AIDS (London, England) Abstract HIV M184V 35 40 NNRTI 45 80 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations, most commonly the 151 complex. 2009 AIDS (London, England) Abstract HIV K65R;K65R;K70E;K70E 54;178;46;186 58;182;50;190 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. However, N348I, A376S and Q509L did confer varying amounts of nevirapine resistance by themselves, even in the absence of EEMs. 2009 Antiviral research Abstract HIV A376S;N348I;Q509L 16;9;26 21;14;31 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Specifically, the E312Q, G333E, G335D, V365I, A371V and A376S substitutions were present in 2-6% of subtype B, whereas the G335D and A371V substitutions were commonly observed in 69% and 75% of non-B HIV-1 isolates. 2009 Antiviral research Abstract HIV A371V;A371V;A376S;E312Q;G333E;G335D;G335D;V365I 46;133;56;18;25;32;123;39 51;138;61;23;30;37;128;44 19430098 Mutations in the thumb-connection and RNase H domain of HIV type-1 reverse transcriptase of antiretroviral treatment-experienced patients. Both R284K and K451R interact with the phosphate backbone of the template or primer in HIV-1 RT crystal structures and could potentially influence the positioning of the primer strand, thus affecting polymerization, the efficiency of nucleoside reverse transcriptase inhibitor excision and/or RNase H activity. 2009 Antiviral therapy Abstract HIV K451R;R284K 15;5 20;10 NRTI;RT 234;93 266;95 19430098 Mutations in the thumb-connection and RNase H domain of HIV type-1 reverse transcriptase of antiretroviral treatment-experienced patients. CONCLUSIONS: RT mutations at three positions outside of the polymerase region were associated with antiretroviral therapy: R284K, N348I and K451R. 2009 Antiviral therapy Abstract HIV K451R;N348I;R284K 140;130;123 145;135;128 Pol;RT 60;13 70;15 19430098 Mutations in the thumb-connection and RNase H domain of HIV type-1 reverse transcriptase of antiretroviral treatment-experienced patients. In treatment-experienced patients, 17.3% had R284K, whereas 24.5% had N348I substitutions. 2009 Antiviral therapy Abstract HIV N348I;R284K 70;45 75;50 19430098 Mutations in the thumb-connection and RNase H domain of HIV type-1 reverse transcriptase of antiretroviral treatment-experienced patients. Within the RNase H domain, only K451 showed a statistically significant change (P99%), both carrying the major IAS PI mutation M46I. 2009 The new microbiologica Abstract HIV M46I 119 123 PI 107 109 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. Among those successfully genotyped, the most frequent mutations were M184I/V (64%), conferring resistance to lamivudine, and K103N (27%), Y181C (27%) and G190A (27%), conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), whereas 23% had thymidine analogue mutations (TAMs), associated with cross-resistance to all nucleoside reverse transcriptase inhibitors (NRTIs). 2009 BMC infectious diseases Abstract HIV G190A;K103N;M184I;M184V;Y181C 154;125;69;69;138 159;130;76;76;143 NNRTI;NRTI;NNRTI;NRTI 192;343;241;388 228;375;247;393 19584504 Drug resistant mutations detected by genotypic drug resistance testing in patients failing therapy in clade C HIV-1 infected individuals from India. Previous reports from India have shown M184V as the commonest mutation in treated individuals. 2009 Indian journal of medical microbiology Abstract HIV M184V 39 44 19584504 Drug resistant mutations detected by genotypic drug resistance testing in patients failing therapy in clade C HIV-1 infected individuals from India. The M46I mutation was seen in 20% of the Pr sequences. 2009 Indian journal of medical microbiology Abstract HIV M46I 4 8 PR 41 43 19584504 Drug resistant mutations detected by genotypic drug resistance testing in patients failing therapy in clade C HIV-1 infected individuals from India. The most common mutation conferring NRTI resistance was M184V (90%) while K103N (45%) was the most common mutation conferring NNRTI resistance. 2009 Indian journal of medical microbiology Abstract HIV K103N;M184V 74;56 79;61 NNRTI;NRTI 126;36 131;40 19591191 Design, synthesis, and SAR of naphthyl-substituted Diarylpyrimidines as non-nucleoside inhibitors of HIV-1 reverse transcriptase. A series of 38 2-naphthyl-substituted diarylpyrimidine (DAPY) analogues, characterized by various substitution patterns on the pyrimidine and naphthalene rings, was synthesized in a straightforward fashion by means of parallel synthesis and evaluated as inhibitors of the HIV-1 wild-type and double mutant (K103N+Y181C) strains. 2009 ChemMedChem Abstract HIV K103N;Y181C 307;313 312;318 19596885 Anti-human immunodeficiency virus activity, cross-resistance, cytotoxicity, and intracellular pharmacology of the 3'-azido-2',3'-dideoxypurine nucleosides. Importantly, both 3'-azido-ddA and 3'-azido-ddG retain activity against viruses containing K65R, L74V, or M184V (IC50 change of <2.0-fold) and against those containing three or more thymidine analog mutations (IC50 change of <3.5-fold). 2009 Antimicrobial agents and chemotherapy Abstract HIV K65R;L74V;M184V 91;97;106 95;101;111 19601778 Clinical validation and applicability of different tipranavir/ritonavir genotypic scores in HIV-1 protease inhibitor-experienced patients. On the contrary, the use of T20 in T20-naive patients and the V82AFSI and F53LY non-IAS mutations were associated with virological success. 2009 Current HIV research Abstract HIV F53L;F53Y;V82A;V82F;V82I;V82S 74;74;62;62;62;62 79;79;69;69;69;69 19601778 Clinical validation and applicability of different tipranavir/ritonavir genotypic scores in HIV-1 protease inhibitor-experienced patients. The following variables were significantly associated (p<0.05) to failure with multivariate analysis: WS, log peak of HIV-RNA, IAS mutations: L33F, I54AMV, Q58E, and non-IAS mutation: N37DES. 2009 Current HIV research Abstract HIV I54A;I54M;I54V;L33F;N37D;N37E;N37S;Q58E 148;148;148;142;184;184;184;156 154;154;154;146;190;190;190;160 19605484 Selective-advantage profile of human immunodeficiency virus type 1 integrase mutants explains in vivo evolution of raltegravir resistance genotypes. After prolonged viral escape, mutants of the N155H pathway are replaced by mutants of the Q148HKR pathway. 2009 Journal of virology Abstract HIV N155H;Q148H;Q148K;Q148R 45;90;90;90 50;97;97;97 19605484 Selective-advantage profile of human immunodeficiency virus type 1 integrase mutants explains in vivo evolution of raltegravir resistance genotypes. Among double mutants, the highest and widest selective-advantage profile was seen with G140S+Q148H. 2009 Journal of virology Abstract HIV G140S;Q148H 87;93 92;98 19605484 Selective-advantage profile of human immunodeficiency virus type 1 integrase mutants explains in vivo evolution of raltegravir resistance genotypes. Despite the higher 50% inhibitory concentration, Q148H displayed a lower and narrower (10 to 100 nM) selective-advantage profile. 2009 Journal of virology Abstract HIV Q148H 49 54 19605484 Selective-advantage profile of human immunodeficiency virus type 1 integrase mutants explains in vivo evolution of raltegravir resistance genotypes. The emergence of human immunodeficiency virus type 1 resistance to raltegravir, an integrase strand transfer inhibitor, follows distinct and independent genetic pathways, among which the N155H and Q148HKR pathways are the most frequently encountered in treated patients. 2009 Journal of virology Abstract HIV N155H;Q148H;Q148K;Q148R 187;197;197;197 192;204;204;204 IN 83 92 19605484 Selective-advantage profile of human immunodeficiency virus type 1 integrase mutants explains in vivo evolution of raltegravir resistance genotypes. These selective-advantage curves revealed that among single mutants, N155H had the highest and the widest (1 to 500 nM) selective-advantage profile. 2009 Journal of virology Abstract HIV N155H 69 74 19605484 Selective-advantage profile of human immunodeficiency virus type 1 integrase mutants explains in vivo evolution of raltegravir resistance genotypes. This finding likely explains why N155H can be selected early in the course of RAL resistance evolution in vivo but is later replaced by genotypes that include Q148HKR. 2009 Journal of virology Abstract HIV N155H;Q148H;Q148K;Q148R 33;159;159;159 38;166;166;166 19605489 Derivation and characterization of a simian immunodeficiency virus SIVmac239 variant with tropism for CXCR4. Only two mutations in the 239-ST1.2-32 Env, K47E in the C1 domain and L328W in the V3 loop, were required for CXCR4 use in cell-cell fusion assays, although two other V3 changes, N316K and I324M, improved CXCR4 use in infection assays. 2009 Journal of virology Abstract HIV I324M;K47E;L328W;N316K 189;44;70;179 194;48;75;184 Env 39 42 19605490 Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. Viral evolution, consisting of new drug resistance mutations and novel amino acid changes within a relevant HLA-restricted allele (e.g., methionine, isoleucine, glutamine, or arginine for leucine at position 205 of RT), was found in 1 and 3 of 20 subjects, respectively. 2009 Journal of virology Abstract HIV L205R 175 211 RT 215 217 19616557 X-ray crystallographic study of an HIV-1 fusion inhibitor with the gp41 S138A substitution. Free-energy calculations suggest that the difference between the desolvation free energies of the C-HR-derived peptides with and without the S138A mutation dominates the observed difference in anti-HIV-1 activity. 2009 Journal of molecular biology Abstract HIV S138A 141 146 19616557 X-ray crystallographic study of an HIV-1 fusion inhibitor with the gp41 S138A substitution. The comparison of the native and S138A crystal structures indicated that the increase in the hydrophobicity of the S138A substitution may aid the stabilization of the N-HR/C-HR complex through additional hydrophobic contacts. 2009 Journal of molecular biology Abstract HIV S138A;S138A 33;115 38;120 19616557 X-ray crystallographic study of an HIV-1 fusion inhibitor with the gp41 S138A substitution. The S138A substitution of fusion inhibitory peptides derived from the C-terminal heptad repeat (C-HR) of the human immunodeficiency virus type 1 (HIV-1) gp41 leads to enhanced binding affinity to the N-terminal heptad repeat (N-HR). 2009 Journal of molecular biology Abstract HIV S138A 4 9 gp41 153 157 19618998 Dynamics of raltegravir resistance profile in an HIV type 2-infected patient. Resistant variants involving the Y143C pathway were noted to have persisted beyond 4 weeks following the cessation of RAL therapy. 2009 AIDS research and human retroviruses Abstract HIV Y143C 33 38 19618998 Dynamics of raltegravir resistance profile in an HIV type 2-infected patient. The treatment failure of an RAL regimen in the HIV-2 patient studied was associated with the emergence of mutations via the N155H resistance pathway and subsequent switching to the Y143C mutational route. 2009 AIDS research and human retroviruses Abstract HIV N155H;Y143C 124;181 129;186 19618998 Dynamics of raltegravir resistance profile in an HIV type 2-infected patient. This study has also identified four novel secondary mutations, Q91R, S147G, A153G, and M183I, not previously reported in HIV-1 patients failing RAL therapy. 2009 AIDS research and human retroviruses Abstract HIV A153G;M183I;Q91R;S147G 76;87;63;69 81;92;67;74 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. The viruses were found to have apoptosis-inducing activity in the order WT > V38M > V38A > G36D > V38E, which correlated with cell-to-cell fusion but not infection. 2009 AIDS research and human retroviruses Abstract HIV G36D;V38A;V38E;V38M 91;84;98;77 95;88;102;81 19623602 HIV-1 IN alternative molecular recognition of DNA induced by raltegravir resistance mutations. Virologic failure during treatment with raltegravir, the first effective drug targeting HIV integrase, is associated with two exclusive pathways involving either Q148H/R/K, G140S/A or N155H mutations. 2009 Journal of molecular recognition Abstract HIV G140A;G140S;N155H;Q148H;Q148K;Q148R 173;173;184;162;162;162 180;180;189;171;171;171 IN 92 101 19625211 Mutation N155H in HIV-2 integrase confers high phenotypic resistance to raltegravir and impairs replication capacity. CONCLUSION: A continued low HIV-2 viral load seems to be enough to select the N155H mutation, which despite significantly impairing viral replication, shows a level of resistance sufficient to give a selective advantage to the virus that maintains this pathway of resistance to raltegravir overtime. 2009 Journal of clinical virology Abstract HIV N155H 78 83 19625211 Mutation N155H in HIV-2 integrase confers high phenotypic resistance to raltegravir and impairs replication capacity. Genotypic analysis at month 8 with raltegravir, revealed the development of N155H resistant mutation along with other changes in the HIV-2 integrase: V72I, I84V, A153G, N160K and S163S/G. 2009 Journal of clinical virology Abstract HIV A153G;I84V;N155H;N160K;S163G;S163S;V72I 162;156;76;169;179;179;150 167;160;81;174;186;186;154 IN 139 148 19625581 The frequency of HIV-I drug resistance mutations among treatment-naive individuals at a tertiary care centre in south India. One strain each had Y181C substitution, T74S and E35G substitutions in the Pr and one had A98G, K101R and L210FL substitutions in RT. 2009 International journal of STD & AIDS Abstract HIV A98G;E35G;K101R;L210F;L210L;T74S;Y181C 90;49;96;106;106;40;20 94;53;101;112;112;44;25 PR;RT 75;130 77;132 19626612 Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. In this study, non-subtype B viruses possessed the K65R mutation at higher incidence than subtype B viruses. 2009 Journal of medical virology Abstract HIV K65R 51 55 19626612 Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. None of the eight viruses with K65R harbored thymidine analogue mutations. 2009 Journal of medical virology Abstract HIV K65R 31 35 19626612 Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. Recently, in vitro studies have shown that K65R is selected in tissue culture more rapidly with subtype C than subtype B viruses. 2009 Journal of medical virology Abstract HIV K65R 43 47 19626612 Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. Seven non-B viruses had the K65R mutation, which was only found in one subtype B virus. 2009 Journal of medical virology Abstract HIV K65R 28 32 19626612 Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. The K65R mutation in HIV-1 reverse transcriptase (RT) can be selected by the RT inhibitors tenofovir (TDF), abacavir (ABC), and didanosine (DDI). 2009 Journal of medical virology Abstract HIV K65R 4 8 RT;RT;RT 27;50;77 48;52;79 19626612 Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel. The prevalence of K65R in viruses sequenced at the Tel-Aviv AIDS Center was evaluated. 2009 Journal of medical virology Abstract HIV K65R 18 22 AIDS 60 64 19627247 Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V. Addition of M46I, which did not confer any lopinavir resistance on its own, had a dual effect. 2009 The Journal of infectious diseases Abstract HIV M46I 12 16 19627247 Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V. Analysis of a large clinical database (>180,000 human immunodeficiency virus [HIV] sequences) demonstrated a significant association (Spearman rho, 0.93) between the increased presence of L76V in clinical samples (0.5% in 2000 to 3.4% in 2006) and lopinavir prescription over time. 2009 The Journal of infectious diseases Abstract HIV L76V 188 192 19627247 Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V. CONCLUSIONS: The HIV protease substitution L76V, in combination with M46I, confers clinically relevant levels of lopinavir resistance and represents a novel resistance pathway to first-line lopinavir/r therapy. 2009 The Journal of infectious diseases Abstract HIV L76V;M46I 43;69 47;73 PR 21 29 19627247 Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V. RESULTS: A detailed longitudinal analysis demonstrated the selection of the M46I+L76V protease mutations in all 3 patients. 2009 The Journal of infectious diseases Abstract HIV L76V;M46I 81;76 85;80 PR 86 94 19627247 Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V. The L76V conferred a solitary 3.5-fold increase in one-half the maximal inhibitory concentration to lopinavir but severely hampered viral replication. 2009 The Journal of infectious diseases Abstract HIV L76V 4 8 19629548 Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. Detailed binding free energies between TMC-114 and individual protein residues are computed by using a per-residue basis decomposition method, which provides insights into the inhibitor-protein binding mechanism and also explains the drug-resistant mechanisms of mutations D30N and I50V to TMC-114. 2010 Journal of molecular modeling Abstract HIV D30N;I50V 273;282 277;286 19629548 Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. In this work, molecular dynamics (MD) simulations combined with the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method have been performed to investigate the drug-resistant mechanisms of D30N and I50V to an inhibitor TMC-114. 2010 Journal of molecular modeling Abstract HIV D30N;I50V 204;213 208;217 19629548 Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. The analyses of absolute binding free energies using the separate trajectory approach suggests that the decrease in the van der Waals energy and electrostatic energy in the gas phase results in the drug resistance of D30N to TMC-114, while for I50V, the decrease in the electrostatic energy mainly drive its drug resistance to TMC-114. 2010 Journal of molecular modeling Abstract HIV D30N;I50V 217;244 221;248 19629548 Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. The single mutations D30N and I50V are considered as the key residue mutations of the HIV-1 protease drug resistance to inhibitors in clinical use. 2010 Journal of molecular modeling Abstract HIV D30N;I50V 21;30 25;34 PR 92 100 19629548 Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: free energy calculation and molecular dynamic simulation. The study shows that the loss of the hydrogen bond between TMC-114 and the side chain of Asn30' is the main driving force of the resistance of D30N to TMC-114, and in the case of I50V, the increase in the polar solvation energies between TMC-114 and two residues Val50' and Asp30' definitively drives the resistance of I50V to TMC-114. 2010 Journal of molecular modeling Abstract HIV D30N;I50V;I50V 143;179;319 147;183;323 Asp 274 277 19637180 Synthesis and anti-HIV-1 activity of 1-substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils. 3-{[3-(Allyloxymethyl)-5-ethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]fluoromethyl}-benzonitrile 11b showed moderate activity against the Y181C HIV-1 mutant strain. 2009 Archiv der Pharmazie Abstract HIV Y181C 142 147 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. CONCLUSIONS: The K65R mutation is increasingly recognized and is a challenging finding among patients with non-B HIV subtypes, whether or not they have been exposed to TDF. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 17 21 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Specific patterns of mutations and clinical characteristics are described in patients with the K65R mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 95 99 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The K65R mutation was present in 37 of 338 patients (10.9%). 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 4 8 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The most common nucleoside reverse transcriptase inhibitor mutations observed were M184V (301, 89.1%) and K70R (91, 26.9%). 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K70R;M184V 106;83 110;88 NRTI 16 48 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The Q151M (P < 0.05), K219R, and T69del (P < 0.01) mutations were more common in patients with K65R who had not received TDF. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K219R;K65R;Q151M;T69del 22;95;4;33 27;99;9;39 19644384 Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naive subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934. Nine of 22 patients with baseline NNRTI-R experienced virologic failure (FTC + TDF + EFV, n = 4; 3TC + ZDV + EFV, n = 5); seven of nine developed M184V/I and/or additional NNRTI-R, but none developed K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;M184I;M184V 200;146;146 204;153;153 NNRTI;NNRTI 34;172 39;177 19644384 Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naive subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934. NNRTI-R, primarily the K103N mutation, was the most common form of resistance that developed in both groups. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 23 28 NNRTI 0 5 19644384 Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naive subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934. No subject on FTC + TDF + EFV developed the K65R mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 44 48 19644384 Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naive subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934. Significantly fewer subjects on FTC + TDF + EFV compared with 3TC + ZDV + EFV developed the M184V/I mutation (two versus 10, respectively, P = 0.021). 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 92;92 99;99 19649847 Calanolides, the naturally occurring anti-HIV agents. Further enhancement of activity is observed with RTs that possess the Y181C change together with AZT-resistant mutations. 2000 Current opinion in drug discovery & development Abstract HIV Y181C 70 75 RT 49 52 19649847 Calanolides, the naturally occurring anti-HIV agents. In cell culture assays, calanolide compounds, especially (+)-calanolide A, select primarily resistant viruses possessing the T139I amino acid change. 2000 Current opinion in drug discovery & development Abstract HIV T139I 125 130 19649847 Calanolides, the naturally occurring anti-HIV agents. Moreover, when challenged with viruses containing Y181C and K103N dual mutations, calanolide compounds remain active. 2000 Current opinion in drug discovery & development Abstract HIV K103N;Y181C 60;50 65;55 19649847 Calanolides, the naturally occurring anti-HIV agents. Of particular interest is the use of calanolide in the treatment of patients who have failed other NNRTI therapy and developed the Y181C mutation or the Y181C/K103N dual mutations. 2000 Current opinion in drug discovery & development Abstract HIV K103N;Y181C;Y181C 159;131;153 164;136;158 NNRTI 99 104 19649847 Calanolides, the naturally occurring anti-HIV agents. These compounds also exhibit an enhanced antiviral activity against one of the most prevalent non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant viruses that is engendered by the Y181C amino acid change in reverse transcriptase (RT). 2000 Current opinion in drug discovery & development Abstract HIV Y181C 193 198 NNRTI;RT;NNRTI;RT 94;220;142;243 130;241;147;245 19651140 Increased thermostability and fidelity of DNA synthesis of wild-type and mutant HIV-1 group O reverse transcriptases. However, a double mutant devoid of RNase H activity (V75I/E478Q) was found to reverse-transcribe at temperatures as high as 68 degrees C, while maintaining the increased accuracy of the V75I mutant. 2009 Journal of molecular biology Abstract HIV V75I;E478Q;V75I 53;58;186 57;63;190 19651140 Increased thermostability and fidelity of DNA synthesis of wild-type and mutant HIV-1 group O reverse transcriptases. In HIV-1 group O RT, substituting Ile75 for Val rendered an enzyme that was 1.9 and 4.7 times more faithful than O_WT RT and BH10_WT RTs, respectively, in forward mutation assays. 2009 Journal of molecular biology Abstract HIV V75I 34 47 RT;RT;RT 17;118;133 19;120;136 19651140 Increased thermostability and fidelity of DNA synthesis of wild-type and mutant HIV-1 group O reverse transcriptases. V75I caused a loss of efficiency of reverse transcription PCR amplifications at 65 and 68 degrees C in comparison with O_WT RT. 2009 Journal of molecular biology Abstract HIV V75I 0 4 RT;RT 36;124 57;126 19651917 Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors. E157Q was the only naturally occurring mutation thought to contribute to resistance to elvitegravir, raltegravir, and L-870,810. 2009 Antimicrobial agents and chemotherapy Abstract HIV E157Q 0 5 19651917 Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors. V72I was the most common, seen in 63 (56.3%) of the AHI samples. 2009 Antimicrobial agents and chemotherapy Abstract HIV V72I 0 4 19651917 Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors. We identified polymorphisms V72I, L74I, T97A, V151I, M154I/L, E157Q, V165I, V201I, I203M, T206S, and S230N. 2009 Antimicrobial agents and chemotherapy Abstract HIV E157Q;I203M;L74I;M154I;M154L;S230N;T206S;T97A;V151I;V165I;V201I;V72I 62;83;34;53;53;101;90;40;46;69;76;28 67;88;38;60;60;106;95;44;51;74;81;32 19654564 Predictors of virologic failure and genotypic resistance mutation patterns in thai children receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. The common NNRTI mutations were Y181C/I (58%) and K103N (34%). 2009 The Pediatric infectious disease journal Abstract HIV K103N;Y181C;Y181I 50;32;32 55;39;39 NNRTI 11 16 19654564 Predictors of virologic failure and genotypic resistance mutation patterns in thai children receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. The NRTI mutations were M184V/I (84%), K65R (11%), Q151M (5%), and >or=3 TAMs (3%). 2009 The Pediatric infectious disease journal Abstract HIV K65R;M184I;M184V;Q151M 39;24;24;51 43;31;31;56 NRTI 4 8 19656870 Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. In HeLa cells, however, treatment with Cs or Cs analogues minimally inhibits the early phase of HIV-1 infection but selects for a Cs-dependent virus with a change (A92E) in CA. 2009 Journal of virology Abstract HIV A92E 164 168 Capsid 173 175 HIV infections 96 111 19656870 Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. In Jurkat T lymphocytes, disrupting CypA-CA interaction either by cyclosporine (Cs) treatment or by alteration (e.g., P90A) of the CA inhibits HIV-1 infection. 2009 Journal of virology Abstract HIV P90A 118 122 Capsid;Capsid 41;131 43;133 HIV infections 143 158 19656870 Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. Reducing the binding of CypA to the A92E mutant capsid, either by Cs treatment or by an additional P90A change in the CA protein, increased the amount of particulate capsids and viral infectivity in HeLa cells. 2009 Journal of virology Abstract HIV A92E;P90A 36;99 40;103 Capsid;Capsid;Capsid 48;166;118 54;173;120 19656870 Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. The A92E change impaired CA-CA interactions in vitro and decreased the amount of particulate capsids in the cytosol of HeLa target cells. 2009 Journal of virology Abstract HIV A92E 4 8 Capsid;Capsid;Capsid 93;25;28 100;27;30 19656870 Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. To understand these phenomena, we examined the effects of the P90A and A92E changes in the HIV-1 CA protein on the stability of capsid complexes assembled in vitro and on capsid disassembly in the cytosol of virus-exposed target cells. 2009 Journal of virology Abstract HIV A92E;P90A 71;62 75;66 Capsid;Capsid;Capsid 128;171;97 134;177;99 19665910 Antiretroviral drug resistance in HIV-infected patients in Colombia. The most common mutations were 184V (n=48; 62.3%), 103N (n=37; 48.1%), G190A/S (n=9; 11.7%), and L90M (n=9; 11.7%). 2010 International journal of infectious diseases Abstract HIV G190A;G190S;L90M 71;71;97 78;78;101 19669091 Effectiveness of antiretroviral regimens containing abacavir with tenofovir in treatment-experienced patients: predictors of virological response and drug resistance evolution in a multi-cohort study. BACKGROUND: In treatment-naive patients, a combination antiretroviral therapy (cART) containing tenofovir (TDF) and abacavir (ABC) with lamivudine leads to unacceptably high virological failure rates with frequent selection of reverse transcriptase mutations M184V and K65R. 2009 Infection Abstract HIV K65R;M184V 269;259 273;264 RT 227 248 19669091 Effectiveness of antiretroviral regimens containing abacavir with tenofovir in treatment-experienced patients: predictors of virological response and drug resistance evolution in a multi-cohort study. Higher viral load and the presence of M41L at baseline were associated with worse virological responses, while the concomitant prescription of drugs enhancing the genetic barrier of the regimen conveyed a reduced risk of virological failure. 2009 Infection Abstract HIV M41L 38 42 19669091 Effectiveness of antiretroviral regimens containing abacavir with tenofovir in treatment-experienced patients: predictors of virological response and drug resistance evolution in a multi-cohort study. In the subset of 136 patients for whom there were genotypic resistance test results prior to ABC + TDF initiation, the virological failure (1-year estimated probability 46%) was independently predicted by the higher baseline viral load, the concomitant use of boosted PI, and the presence of reverse transcriptase mutation M41L. 2009 Infection Abstract HIV M41L 323 327 RT;PI 292;268 313;270 19669091 Effectiveness of antiretroviral regimens containing abacavir with tenofovir in treatment-experienced patients: predictors of virological response and drug resistance evolution in a multi-cohort study. No selection of K65R was detected. 2009 Infection Abstract HIV K65R 16 20 19681953 Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy. Analysis of PBMC DNA should be considered when searching for residual K103N mutant species in patients previously exposed to NNRTIs. 2010 Clinical microbiology and infection Abstract HIV K103N 70 75 NNRTI 125 131 19681953 Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy. Following discontinuation of NNRTI therapy for a median of 55.9 weeks and a decrease of K103N mutant species to undetectable levels in plasma RNA, minority K103N species remained detectable, by allele-specific PCR, for longer periods of time and at higher frequency, in peripheral blood mononuclear cell (PBMC) DNA than in plasma RNA (76.7% and 46.7% of samples with residual K103N species detected at median frequencies of 18.0% and 3.8%, respectively). 2010 Clinical microbiology and infection Abstract HIV K103N;K103N;K103N 88;156;376 93;161;381 NNRTI 29 34 19681953 Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy. Non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy failed in 30 patients with the typical human immunodeficiency virus type 1 reverse transcriptase K103N mutation, detected using standard genotyping. 2010 Clinical microbiology and infection Abstract HIV K103N 160 165 NNRTI;RT;NNRTI 0;138;48 36;159;53 19682948 HIV-1 pol phylogenetic diversity and antiretroviral resistance mutations in treatment naive patients from Central West Brazil. T215D/S revertant mutations were identified in 4/97 patients. 2009 Journal of clinical virology Abstract HIV T215D;T215S 0;0 7;7 19689192 Epidemiological networks and drug resistance of HIV type 1 in Krasnoyarsk region, Russia. Most viruses (75%) had an A62V mutation in reverse transcriptase, specific for HIV-1 strains in Russia. 2009 AIDS research and human retroviruses Abstract HIV A62V 26 30 RT 43 64 19697403 Analysis of the diversity of the HIV-1 pol gene and drug resistance associated changes among drug-naive patients in Burkina Faso. Subtype specific secondary polymorphisms such as K20I and M36I in the PR were observed in almost all patients. 2009 Journal of medical virology Abstract HIV K20I;M36I 49;58 53;62 PR 70 72 19697403 Analysis of the diversity of the HIV-1 pol gene and drug resistance associated changes among drug-naive patients in Burkina Faso. The mutations were distributed as follows: NRTI (10.6%): M41L (n = 2), D67N (n = 2), K70K/E (n = 2), L210W (n = 1), T215S/Y (n = 2), and K219K/Q (n = 2); NNRTI (6.1%): K103K/N (n = 2), Y181C (n = 2), G190G/A (n = 1), and P236P/L (n = 1). 2009 Journal of medical virology Abstract HIV D67N;G190A;G190G;K103K;K103N;K219K;K219Q;K70E;K70K;L210W;M41L;P236L;P236P;T215S;T215Y;Y181C 71;200;200;168;168;137;137;85;85;101;57;221;221;116;116;185 75;207;207;175;175;144;144;91;91;106;61;228;228;123;123;190 NNRTI;NRTI 154;43 159;47 19698024 Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province. E53D (97%), I135V/T/R (81%), S162C (94%), Q207E (100%), and R211K (97%) were primarily in CRF_08BC subtypes and D121Y/H (97%) were primarily in CRF_07BC. 2009 AIDS research and human retroviruses Abstract HIV D121H;D121Y;I135R;I135T;I135V;Q207E;R211K;S162C;E53D 112;112;12;12;12;42;60;29;0 119;119;21;21;21;47;65;34;4 19698024 Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province. Five high polymorphisms were found in CRF_07BC isolates; there were E35D (88%), R41K (100%), D60E (96%), L63P (99%), and I93L (91%). 2009 AIDS research and human retroviruses Abstract HIV D60E;E35D;I93L;L63P;R41K 93;68;121;105;80 97;72;125;109;84 19698024 Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province. Four of the identified polymorphism positions (R41K, D60E, L63P, and I93L) were the same in the PR region of both subtypes. 2009 AIDS research and human retroviruses Abstract HIV D60E;I93L;L63P;R41K 53;69;59;47 57;73;63;51 PR 96 98 19698024 Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province. In the reverse transcriptase (RT) region six high polymorphism positions, V35T, E36A, T39D/E/N, S48T, V60I, and V245Q, were identified in both subtypes. 2009 AIDS research and human retroviruses Abstract HIV E36A;S48T;T39D;T39E;T39N;V245Q;V35T;V60I 80;96;86;86;86;112;74;102 84;100;94;94;94;117;78;106 RT;RT 7;30 28;32 19698024 Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province. Polymorphisms V77M (PI) and K201Q (RT) were not found in the mutation profiles; therefore it may have been a new mutation in HIV-1. 2009 AIDS research and human retroviruses Abstract HIV K201Q;V77M 28;14 33;18 PI;RT 20;35 22;37 19698024 Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province. The NRTI resistance mutation T69S was 94% (30/32) in CRF_08BC. 2009 AIDS research and human retroviruses Abstract HIV T69S 29 33 NRTI 4 8 19698024 Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province. The polymorphisms L19I, M36I, R41K, D60E, L63P, H69K, and I93L were complete substitutions, and were followed by T12S (94%), I15V (90%), and L89M (81%) separately. 2009 AIDS research and human retroviruses Abstract HIV D60E;H69K;I15V;I93L;L19I;L63P;L89M;M36I;R41K;T12S 36;48;125;58;18;42;141;24;30;113 40;52;129;62;22;46;145;28;34;117 19704127 Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine. Both the biochemical and the cell-based phenotypic assays confirmed the susceptibility of G190A-containing enzymes and viruses to ETR. 2009 Antimicrobial agents and chemotherapy Abstract HIV G190A 90 95 19704127 Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine. Recombinant HIV-1 RT enzymes containing either the Y181C or the G190A mutation, or both mutations in tandem, were purified. 2009 Antimicrobial agents and chemotherapy Abstract HIV G190A;Y181C 64;51 69;56 RT 18 20 19704127 Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine. The results of this study indicate that the G190A mutation is not associated with resistance to ETR. 2009 Antimicrobial agents and chemotherapy Abstract HIV G190A 44 49 19704127 Human immunodeficiency virus type 1 recombinant reverse transcriptase enzymes containing the G190A and Y181C resistance mutations remain sensitive to etravirine. This study was designed to determine the extent to which each of the Y181C or G190A mutations in RT might confer resistance to ETR and other members of the NNRTI family of drugs. 2009 Antimicrobial agents and chemotherapy Abstract HIV G190A;Y181C 78;69 83;74 NNRTI;RT 156;97 161;99 19704131 Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. M184V may be the primary resistance-associated mutation of 4'-Ed4T, and P119S and T165A are secondary mutations. 2009 Antimicrobial agents and chemotherapy Abstract HIV P119S;T165A;M184V 72;82;0 77;87;5 19704131 Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. Previous in vitro selection for 4'-Ed4T-resistant viral strains revealed M184V and P119S/T165A/M184V mutations on days 26 and 81, respectively; M184V and P119S/T165A/M184V conferred 3- and 130-fold resistance to 4'-Ed4T, respectively. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V;P119S;P119S;T165A;T165A;M184V;M184V 95;166;83;154;160;89;73;144 100;171;88;159;165;94;78;149 19704131 Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. The P119S/M184V and T165A/M184V variants showed about fourfold resistance to 4'-Ed4T. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V;P119S;T165A 26;10;4;20 31;15;9;25 19704131 Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. The previously observed 130-fold resistance of the virus with P119S/T165A/M184V to 4'-Ed4T may be partly due to mutations both in the RT sequence and outside the RT sequence. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184V;P119S;T165A 74;62;68 79;67;73 RT;RT 134;162 136;164 19704131 Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. The purified RT of mutants with the P119S/M184V and T165A/M184V mutations were inhibited by 4'-Ed4TTP with 8- to 13-fold less efficiency than wild-type RT. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V;P119S;T165A 58;42;36;52 63;47;41;57 RT;RT 13;152 15;154 19704131 Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile. Viral variants with single RT mutations (P119S or T165A) did not show resistance to 4'-Ed4T; however, M184V and P119S/T165A/M184V conferred three- and fivefold resistance, respectively, compared with that of the wild-type virus. 2009 Antimicrobial agents and chemotherapy Abstract HIV M184V;P119S;T165A;M184V;P119S;T165A 124;112;118;102;41;50 129;117;123;107;47;55 RT 27 29 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. K103N was the most common mutation (7.5%). 2009 Antiviral therapy Abstract HIV K103N 0 5 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. Thymidine analogue mutations were found in 4.7% of samples; the most common PI SDRM was L90M (2.4%). 2009 Antiviral therapy Abstract HIV L90M 88 92 PI 76 78 19706699 Human immunodeficiency virus type 1 protease-correlated cleavage site mutations enhance inhibitor resistance. Several patterns were frequently observed, including mutations in the NC-p1 cleavage site in combination with I50L, V82A, and I84V within the protease and mutations within the p1-p6 cleavage site in combination with D30N, I50V, and I84V within the protease. 2009 Journal of virology Abstract HIV D30N;I50L;I50V;I84V;I84V;V82A 216;110;222;126;232;116 220;114;226;130;236;120 PR;PR;NC;Gag 142;248;70;179 150;256;72;181 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. CONCLUSIONS: Our results suggest that T74S is not a major drug resistance mutation, but it resensitizes multiresistant viruses to certain PIs. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 38 42 PI 138 141 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. In this study, we assessed the impact of the protease substitution T74S on the phenotype and on the replicative fitness in HIV-1 subtypes B and C. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 67 71 PR 45 53 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. METHODS: HIV-1 molecular clones carrying subtype B or C proteases had these coding regions subjected to site-directed mutagenesis to include T74S alone or in combination with four known protease inhibitor (PI) primary drug resistance mutations. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 141 145 PR;PR;PI 56;186;206 65;194;208 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. RESULTS: Viruses of both subtypes carrying T74S did not have their susceptibility altered to any tested PI. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 43 47 PI 104 106 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. Surprisingly, the addition of T74S to the multiresistant clones restored their susceptibilities to indinavir and ritonavir and partially to lopinavir, close to those of wild-type viruses. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 30 34 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. T74S is a bona fide accessory mutation, restoring fitness of multidrug-resistant viruses in both subtypes B and C. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 0 4 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. T74S should be further studied in clinical settings and considered in drug resistance interpretation algorithms. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 0 4 19710076 Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and indinavir and confers fitness advantage. The impact of T74S on virus fitness was also assessed for all viruses through head-to-head competitions and oligonucleotide ligation assays to measure the proportion of each virus in culture. 2009 The Journal of antimicrobial chemotherapy Abstract HIV T74S 14 18 19720046 Resistance mechanism revealed by crystal structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S. N88D and N88S are two such mutations which occur in the non-active site region of the enzyme. 2009 Biochemical and biophysical research communications Abstract HIV N88S;N88D 9;0 13;4 19720046 Resistance mechanism revealed by crystal structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S. We have determined crystal structures of unliganded N88D and N88S mutants of HIV-1 protease to resolution of 1.65A and 1.8A, respectively. 2009 Biochemical and biophysical research communications Abstract HIV N88D;N88S 52;61 56;65 PR 83 91 19720046 Resistance mechanism revealed by crystal structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S. While structural effects of N88D are very subtle, the mutation N88S has caused a significant conformational change in D30, an active site residue crucial for substrate and inhibitor binding. 2009 Biochemical and biophysical research communications Abstract HIV N88D;N88S 28;63 32;67 19721100 Primary HIV-1 drug resistance and polymorphic patterns among injecting drug users (IDUs) in Chennai, Southern India. RESULTS: M41LM (1.8%), K65KN (1.8%), and G73GS (2.7%) were found to be associated with low-level resistance to zidovudine (ZDV), stavudine (d4T), abacavir (ABC), didanosine (ddI), emtricitabine (FTC), tenofovir (TDF), and saquinavir (SQV) in each specimen. 2009 Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. Abstract HIV G73G;G73S;K65K;K65N;M41L;M41M 41;41;23;23;9;9 46;46;28;28;14;14 19732174 Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS). Differences in prevalence among subtypes were found for V90I and V179T (P<0.001). 2009 HIV medicine Abstract HIV V179T;V90I 65;56 70;60 19732174 Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS). The presence of major IAS-USA mutations (L100I, K101E/H/P and Y181C/I/V) reduced the treatment response at week 24. 2009 HIV medicine Abstract HIV K101E;K101H;K101P;L100I;Y181C;Y181I;Y181V 48;48;48;41;62;62;62 57;57;57;46;71;71;71 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. 7 of 20 patients failing an NNRTI-containing regimen had minority variants with major etravirine-associated NNRTI-resistant mutations (P = 0.03, Fisher exact test): Y181C (7.0%), Y181C (3.6%) + G190A (3.2%), L100I (14%), L100I (32%) + 190A (5.4%), K101E (3.8%) + G190A (4.9%), K101E (4.0%) + G190S (4.8%), and G190S (3.1%). 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G190A;G190A;G190S;G190S;K101E;K101E;L100I;L100I;Y181C;Y181C 194;263;292;310;248;277;208;221;165;179 199;268;297;315;253;282;213;226;170;184 NNRTI;NNRTI 28;108 33;113 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. CONCLUSIONS: In treatment-naive patients, UDPS did not detect additional major NNRTI-resistant mutations suggesting that etravirine may be effective in patients with transmitted K103N. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 178 183 NNRTI 79 84 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. In NNRTI-experienced patients, UDPS often detected additional major NNRTI-resistant mutations suggesting that etravirine may not be fully active in patients with acquired K103N. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 171 176 NNRTI;NNRTI 3;68 8;73 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. METHODS: We performed ultradeep pyrosequencing (UDPS; 454 Life Sciences a Roche Company, Branford, CT) of plasma virus samples from 13 treatment-naive and 20 NNRTI-experienced patients in whom standard genotypic resistance testing revealed K103N but no other major NNRTI-resistance mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 240 245 NNRTI;NNRTI 158;265 163;270 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. OBJECTIVES: K103N, the most common nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutation in patients with transmitted resistance and in patients receiving a failing NNRTI-containing regimen, is fully susceptible to the new NNRTI, etravirine. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 12 17 NNRTI;NNRTI;NNRTI;NNRTI 35;82;184;242 70;87;189;247 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Therefore, we sought to determine how often NNRTI-resistant mutations other than K103N occur as minority variants in plasma samples for which standard genotypic resistance testing detects K103N alone. 2009 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;K103N 81;188 86;193 NNRTI 44 49 19759140 Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency virus type 1 clade A1 p24. Instead, P243T and I247L were selected by clade A1-infected HLA-B*57 subjects but not by HLA-B*5801(+) subjects. 2009 Journal of virology Abstract HIV I247L;P243T 19;9 24;14 19759140 Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency virus type 1 clade A1 p24. Our data suggest that clade A1 consensus proline at Gag residue 243 might represent an inherent block to T242N escape in clade A1. 2009 Journal of virology Abstract HIV T242N 105 110 Gag 52 55 19759140 Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency virus type 1 clade A1 p24. We confirmed immunologically that P243T and I247L likely represent escape mutations. 2009 Journal of virology Abstract HIV I247L;P243T 44;34 49;39 19759140 Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency virus type 1 clade A1 p24. Whether this T242N pathway is shared by all clades remains unknown. 2009 Journal of virology Abstract HIV T242N 13 18 19759140 Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency virus type 1 clade A1 p24. While T242N was ubiquitous in clade D HLA-B*57(+) subjects, this mutation was rare (15%) in clade A1. 2009 Journal of virology Abstract HIV T242N 6 11 19759152 Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. Analysis of site-directed mutants indicated that E92Q in combination with N155H resulted in a higher level of resistance to raltegravir than N155H alone. 2009 Journal of virology Abstract HIV E92Q;N155H;N155H 49;74;141 53;79;146 19759152 Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. Both N155H and Q148R(H)(K) mutations reduced the replication capacity, while the addition of secondary mutations either improved or reduced the replication capacity depending on the primary mutation. 2009 Journal of virology Abstract HIV N155H;Q148R 5;15 10;20 19759152 Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. Clonal analysis demonstrated that N155H and Q148R(H)(K) occur independently, not in combination. 2009 Journal of virology Abstract HIV N155H;Q148R 34;44 39;49 19759152 Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. The human immunodeficiency virus type 1 (HIV-1) integrase mutations N155H and Q148R(H)(K) that reduce susceptibility to the integrase inhibitor raltegravir have been identified in patients failing treatment regimens containing raltegravir. 2009 Journal of virology Abstract HIV N155H;Q148R 68;78 73;83 IN;IN 48;124 57;133 19759152 Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. Viruses containing a Q148R(H) mutation together with a G140S mutation were more resistant to raltegravir than viruses containing a Q148R(H) mutation alone; however, viruses containing G140S and Q148K were more susceptible to raltegravir than viruses containing a Q148K mutation alone. 2009 Journal of virology Abstract HIV G140S;G140S;Q148K;Q148K;Q148R;Q148R 55;184;194;263;21;131 60;189;199;268;26;136 19759152 Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. Viruses containing a Q148R(H)(K) mutation generally displayed larger reductions in raltegravir susceptibility than viruses with an N155H mutation. 2009 Journal of virology Abstract HIV N155H;Q148R 131;21 136;26 19759509 The prevalence of resistance-associated mutations to protease and reverse transcriptase inhibitors in treatment-naive (HIV1)-infected individuals in Casablanca, Morocco. Only one patient of 70 (1.4%) carried the F77L mutation that is associated with NRTIs resistance. 2009 Journal of infection in developing countries Abstract HIV F77L 42 46 NRTI 80 85 19759509 The prevalence of resistance-associated mutations to protease and reverse transcriptase inhibitors in treatment-naive (HIV1)-infected individuals in Casablanca, Morocco. Only two major mutations, M46L and V82L, were separately found in three individuals of 71 (4.2%) with one carrying both mutations. 2009 Journal of infection in developing countries Abstract HIV M46L;V82L 26;35 30;39 19764886 Signature nucleotide polymorphisms at positions 64 and 65 in reverse transcriptase favor the selection of the K65R resistance mutation in HIV-1 subtype C. Recently, we described a novel nucleotide template-based mechanism that may be the basis for the facilitated acquisition of the K65R resistance mutation in subtype C versus subtype B human immunodeficiency virus type 1 (HIV-1). 2009 The Journal of infectious diseases Abstract HIV K65R 128 132 19764886 Signature nucleotide polymorphisms at positions 64 and 65 in reverse transcriptase favor the selection of the K65R resistance mutation in HIV-1 subtype C. The K65R pathway was selected more frequently in a subtype B virus that contained subtype C nucleotide polymorphisms at both positions 64 and 65 than in a wild-type NL4-3 subtype B virus. 2009 The Journal of infectious diseases Abstract HIV K65R 4 8 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. Efavirenz resistance mutations (especially K103N) can be selected during long-term treatment, underscoring the importance of good adherence. 2009 The Journal of antimicrobial chemotherapy Abstract HIV K103N 43 48 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. We show that the ancestral cyclophilin A (CypA) domain of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in RhTC by two mutations (D66N and R69H) at the expense of HIV-1 binding. 2009 Nature structural & molecular biology Abstract HIV D66N;R69H 158;167 163;171 Capsid 77 83 19769157 [The impact of the HIV-1 envelope (Env) mutation on its assembly of functional pseudovirus]. To find out whether the mutations of HIV-1 Env have influence on the assembly of pseudovirus and their abilities to infect cells, site-directed mutation (A457D)was performed using cycling mutagenesis and selection of mutants with DpnI. 2009 Bing du xue bao Abstract HIV A457D 154 159 Env 43 46 19770695 The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates. OBJECTIVE: : Resistance to raltegravir is associated with three genetic pathways defined by the mutations Y143R/C, Q148H/R/K or N155H in integrase, which also infer a viral fitness cost. 2010 AIDS (London, England) Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 128;115;115;115;106;106 133;124;124;124;113;113 IN 137 146 19770695 The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates. The first had the mutations G140S+Q148H+S230N, the second had Y143R+G163R and the third had no evidence of genotypic resistance in integrase. 2010 AIDS (London, England) Abstract HIV G140S;G163R;Q148H;S230N;Y143R 28;68;34;40;62 33;73;39;45;67 IN 131 140 19775780 Activity and molecular modeling of a new small molecule active against NNRTI-resistant HIV-1 mutants. The molecular modeling strategy adopted yielded a rationale, in terms of molecular interactions and free energy of binding, for the possible reasons of the activity of this compound against NNRTI-resistant HIV-1 mutants with the RT isoforms K103N and Y181C. 2009 European journal of medicinal chemistry Abstract HIV K103N;Y181C 241;251 246;256 NNRTI;RT 190;229 195;231 19776131 Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc. Notably, an additional Q315E/I317F substitution in the crown region of the V3 loop enhanced resistance to VCV, resulting in a stronger dependence on the N terminus for viral entry. 2009 Journal of virology Abstract HIV I317F;Q315E 29;23 34;28 19776131 Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc. RU570-VCV(res) pseudovirus entry with VCV-bound CCR5 was dramatically reduced by Y10A, D11A, Y14A, and Y15A mutations in the N terminus of CCR5, whereas these mutations had less impact on entry in the absence of VCV. 2009 Journal of virology Abstract HIV D11A;Y10A;Y14A;Y15A 87;81;93;103 91;85;97;107 19776131 Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc. The K305R amino acid change primarily impacted the degree of resistance, whereas K319T contributed to both resistance and virus infectivity. 2009 Journal of virology Abstract HIV K305R;K319T 4;81 9;86 19776131 Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc. The P437S mutation in C4 had more influence on the relative degree of virus infectivity, while the R315Q mutation contributed to the virus concentration-dependent phenotypic resistance pattern observed for RU570-VCV(res). 2009 Journal of virology Abstract HIV P437S;R315Q 4;99 9;104 19776131 Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc. We show that K305R, R315Q, and K319T amino acid changes in the V3 loop, along with P437S in C4, completely reproduced the resistance phenotype in a chimeric ADA envelope containing the C2-V5 region from RU570 passage control gp120. 2009 Journal of virology Abstract HIV K305R;K319T;P437S;R315Q 13;31;83;20 18;36;88;25 Env;gp120 161;225 169;230 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wild-type and mutant type enzymes, K103N and Y181C. 2009 Beilstein journal of organic chemistry Abstract HIV K103N;Y181C 162;172 167;177 RT 88 109 19778270 Response to nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-infected children with perinatal exposure to single-dose nevirapine. In 10 children with perinatal exposure to single-dose nevirapine, NNRTI resistance mutations, mostly K103N, Y181C, and G109A, were identified. 2009 AIDS research and human retroviruses Abstract HIV G109A;K103N;Y181C 119;101;108 124;106;113 NNRTI 66 71 1978941 Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. In contrast, the mutation P48S affected neither gp120 binding, nor class II MHC binding, nor T-cell activation. 1990 Proc Natl Acad Sci U S A Abstract HIV P48S 26 30 gp120 48 53 1978941 Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. The mutants d42-49, Q40P, F43L, and G47R lost both gp120 and class II MHC binding as well as the ability to enhance T-cell activation. 1990 Proc Natl Acad Sci U S A Abstract HIV F43L;G47R;Q40P 26;36;20 30;40;24 gp120 51 56 1978941 Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. The mutation Q40P (Gln40----Pro) and the deletion d42-49 were found to disrupt most antibody epitopes in the V1 domain of CD4, suggesting major conformational changes, whereas mutants F43L, G47R, and P48S retained the binding of most of the anti-CD4 antibodies tested. 1990 Proc Natl Acad Sci U S A Abstract HIV F43L;G47R;P48S;Q40P;Q40P 184;190;200;13;19 188;194;204;17;31 19793805 The cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein gp41 harbors lipid raft association determinants. With the exception of a Pro substitution for Val-833, all Pro substitution and charge-inverting mutants showed wild-type virus-like one-cycle viral infectivity, replication kinetics, and Env incorporation into the virus. 2010 Journal of virology Abstract HIV V833P 24 52 Env 187 190 19798742 Revealing the dimer dissociation and existence of a folded monomer of the mature HIV-2 protease. Addition of twofold excess active-site inhibitor promotes dimerization of PR2(T26A) but not of PR2(1-95), indicating that subunit interactions involving the C-terminal residues are crucial for dimer formation. 2009 Protein science Abstract HIV T26A 78 82 PR;PR 74;95 77;98 19798742 Revealing the dimer dissociation and existence of a folded monomer of the mature HIV-2 protease. An E37K substitution in PR2 significantly retards autoproteolytic cleavage during expression. 2009 Protein science Abstract HIV E37K 3 7 PR 24 27 19798742 Revealing the dimer dissociation and existence of a folded monomer of the mature HIV-2 protease. Dimer interface mutations, such as a T26A substitution in the active site (PR2(T26A)) or a deletion of the C-terminal residues 96-99 (PR2(1-95)), drastically increase the K(d) (>10(5)-fold). 2009 Protein science Abstract HIV T26A;T26A 37;79 41;83 PR;PR 75;134 78;137 19798742 Revealing the dimer dissociation and existence of a folded monomer of the mature HIV-2 protease. Furthermore, it permits convenient measurement of the dimer dissociation of PR2(E37K) (elevated K(d) approximately 20 nM) by enzyme kinetics. 2009 Protein science Abstract HIV E37K 80 84 PR 76 79 19798742 Revealing the dimer dissociation and existence of a folded monomer of the mature HIV-2 protease. PR2(T26A) and PR2(1-95) consist predominantly of folded monomers, as determined by nuclear magnetic resonance (NMR) and size-exclusion chromatography coupled with multiangle light scattering and refractive index measurements (SMR), whereas wild-type PR2 and its active-site mutant PR2(D25N) are folded dimers. 2009 Protein science Abstract HIV D25N;T26A 285;4 289;8 PR;PR;PR;PR 0;14;250;281 3;17;253;284 19799008 [Study of Gag gene antigen epitypes variation and the quasispecies group characteristics in Henan area HIV-1 strains]. RESULTS: B' subtype strains were predominant in Henan province, the mutations in antigen epitypes of the p17 region of the gag gene focus on E62g (55.8%), Y79f (48.9%), T84V (48.9), I44V (44.2%), the p24 region had not found the distinct mutation. 2009 Zhonghua shi yan he lin chuang bing du xue za zhi Abstract HIV I44V;T84V 182;169 186;173 p24;Gag 200;123 203;126 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. In a wild-type HIV-1 group O RT sequence context, V75A and V75M conferred increased excision activity on d4T-terminated primers, in the presence of PP(i). 2009 The Journal of biological chemistry Abstract HIV V75A;V75M 50;59 54;63 RT 29 31 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. In contrast, V75I decreased the PP(i)-mediated unblocking efficiency on AZT and d4T-terminated primers, in different sequence contexts. 2009 The Journal of biological chemistry Abstract HIV V75I 13 17 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. M41L/A62V/T69SSS/K70R/T215Y), the introduction of V75I led to a significant decrease of its ATP-dependent excision activity on AZT-, d4T-, and acyclovir-terminated primers. 2009 The Journal of biological chemistry Abstract HIV A62V;K70R;M41L;T215Y;T69SSS;V75I 5;17;0;22;10;50 9;21;4;27;16;54 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. Mutations, such as V75M and V75A, emerge in patients infected with HIV-1 group M subtype B and group O variants, after failing treatment with stavudine (d4T) and other nucleoside RT inhibitors. 2009 The Journal of biological chemistry Abstract HIV V75A;V75M 28;19 32;23 RT 179 181 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. Recombinant HIV-1 containing the M41L/A62V/T69SSS/K70R/V75I/T215Y RT showed 18.3- and 1.5-fold increased susceptibility to AZT and d4T, respectively, in comparison with virus containing the M41L/A62V/T69SSS/K70R/T215Y RT. 2009 The Journal of biological chemistry Abstract HIV A62V;A62V;K70R;K70R;M41L;M41L;T215Y;T215Y;T69SSS;T69SSS;V75I 195;38;50;207;33;190;60;212;43;200;55 199;42;54;211;37;194;65;217;49;206;59 RT;RT 66;218 68;220 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. The antagonistic effect of V75I with TAMs was further demonstrated in phenotypic assays. 2009 The Journal of biological chemistry Abstract HIV V75I 27 31 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. The excision rate of d4T-monophosphate in the presence of ATP (3.2 mm) was about 10 times higher for M41L/A62V/T69SSS/K70R/T215Y than for the mutant M41L/A62V/T69SSS/K70R/V75I/T215Y RT. 2009 The Journal of biological chemistry Abstract HIV A62V;A62V;K70R;K70R;M41L;M41L;T215Y;T215Y;T69SSS;T69SSS;V75I 154;106;118;166;101;149;123;176;111;159;171 158;110;122;170;105;153;128;181;117;165;175 RT 182 184 19801659 Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination. V75I is an accessory mutation of the Q151M multidrug resistance complex of HIV-1 RT and is rarely associated with thymidine analogue resistance mutations (TAMs). 2009 The Journal of biological chemistry Abstract HIV Q151M;V75I 37;0 42;4 RT 81 83 19801944 Varied patterns of HIV-1 drug resistance on failing first-line antiretroviral therapy in South Africa. RESULTS: The most common reverse transcriptase mutation was M184V/I (72%; n = 163); 11% of patients (n = 25) had only nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations and 17% (n = 38) had no known resistance mutations. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 60;60 67;67 NNRTI;RT;NNRTI 118;25;165 153;46;170 19801944 Varied patterns of HIV-1 drug resistance on failing first-line antiretroviral therapy in South Africa. The K65R mutation was detected in 4%. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 4 8 19801944 Varied patterns of HIV-1 drug resistance on failing first-line antiretroviral therapy in South Africa. The V106M mutation was more frequent with EFV (30%) than NVP (4%; P = 0.012). 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V106M 4 9 19801944 Varied patterns of HIV-1 drug resistance on failing first-line antiretroviral therapy in South Africa. The Y181C mutation was more frequent with failure of nevirapine (NVP)-containing (26%) than efavirenz (EFV)-containing therapy (3%; P < 0.001). 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Y181C 4 9 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Furthermore, the guanidinium planes of K65R and Arg(72) were stacked in two different rotameric conformations in TFV-DP- and dATP-bound structures that may help explain how K65R RT discriminates the drug from substrates. 2009 The Journal of biological chemistry Abstract HIV K65R;K65R 39;173 43;177 RT 178 180 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R is a primary reverse transcriptase (RT) mutation selected in human immunodeficiency virus type 1-infected patients taking antiretroviral regimens containing tenofovir disoproxil fumarate or other nucleoside analog RT drugs. 2009 The Journal of biological chemistry Abstract HIV K65R 0 4 RT;RT;RT 18;41;219 39;43;221 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The guanidinium planes of the arginines K65R and Arg(72) were stacked to form a molecular platform that restricts the conformational adaptability of both of the residues, which explains the negative effects of the K65R mutation on nucleotide incorporation and on excision. 2009 The Journal of biological chemistry Abstract HIV K65R;K65R 40;214 44;218 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. These K65R-mediated effects on RT structure and function help us to visualize the complex interaction with other key nucleotide RT drug resistance mutations, such as M184V, L74V, and thymidine analog resistance mutations. 2009 The Journal of biological chemistry Abstract HIV K65R;L74V;M184V 6;173;166 10;177;171 RT;RT 31;128 33;130 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. We determined the crystal structures of K65R mutant RT cross-linked to double-stranded DNA and in complexes with tenofovir diphosphate (TFV-DP) or dATP. 2009 The Journal of biological chemistry Abstract HIV K65R 40 44 RT 52 54 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Among mutations that confer resistance to antiretroviral drugs, M184V was present in 76% of treated patients and K70R in 31% (A-->G transitions). 2005 Journal of the International AIDS Society Abstract HIV K70R;M184V 113;64 117;69 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. In PR, a L90M (T-->A substitution) was prevalent in 47% of protease inhibitor (PI)-treated patients. 2005 Journal of the International AIDS Society Abstract HIV L90M 9 13 PR;PI;PR 59;79;3 67;81;5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Other frequent mutations in RT included T215Y (C-->A and A-->T substitutions), which was prevalent in 31% of treated patients. 2005 Journal of the International AIDS Society Abstract HIV T215Y 40 45 RT 28 30 19838125 Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection. BACKGROUND: The M184V mutation decreases the replication capacity of HIV-1. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 16 21 19838125 Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection. METHODS: Clinically stable patients with CD4 cells greater than 300/microL, previous virologic failure, and a M184V mutation were treated with 3TC 300 mg once daily during 48 weeks. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 110 115 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. In contradiction with published results, the R77Q substitution, found in LTNP alleles, did not influence Vpr proapoptotic activity. 2009 PloS one Abstract HIV R77Q 45 49 Vpr 105 108 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. They displayed cytostatic and proapoptotic activities, although a LTNP allele, harboring the Q65R substitution, failed to bind the DCAF1 subunit of the Cul4a/DDB1 E3 ligase and was inactive. 2009 PloS one Abstract HIV Q65R 93 97 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. This Q65R substitution correlated with impairment of Vpr docking at the nuclear envelope, raising the possibility of a functional link between this property and the Vpr cytostatic activity. 2009 PloS one Abstract HIV Q65R 5 9 Env;Vpr;Vpr 80;53;165 88;56;168 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. Mutant proteins 1-279/F185K and 1-276/F185K are therefore highlighted as potential structural biology candidates, whereas further deleted tail variants (1-273/F185K or 1-270/F185K) are less desirable due to marginal or undetectable levels of integrase function. 2009 Retrovirology Abstract HIV F185K;F185K;F185K;F185K 22;38;159;174 27;43;164;179 IN 242 251 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. The F185K core domain mutation, which increases integrase protein solubility, was furthermore analyzed in a subset of mutants. 2009 Retrovirology Abstract HIV F185K 4 9 IN 48 57 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. The F185K mutation reduced the in vitro activities of 1-279 and 1-276 integrases by about 25%. 2009 Retrovirology Abstract HIV F185K 4 9 IN 70 80 19842792 Changes in drug resistance patterns following the introduction of HIV type 1 non-B subtypes in Spain. K103N was most frequent in B than non-B subtypes (34% vs. 2009 AIDS research and human retroviruses Abstract HIV K103N 0 5 19852859 Five-year follow up of genotypic resistance patterns in HIV-1 subtype C infected patients in Botswana after failure of thymidine analogue-based regimens. Both major patterns of thymidine analogue mutations, TAM 1 (48%) and TAM 2 (59%), were represented in patients from Group 1 and 2, although M184V was higher among individuals who had initially received ddI (61% versus 40.5%). 2009 Journal of the International AIDS Society Abstract HIV M184V 140 145 19852859 Five-year follow up of genotypic resistance patterns in HIV-1 subtype C infected patients in Botswana after failure of thymidine analogue-based regimens. In contrast, L74V was more frequent among individuals from Group 2 (16.2% versus 7.7%). 2009 Journal of the International AIDS Society Abstract HIV L74V 13 17 19852859 Five-year follow up of genotypic resistance patterns in HIV-1 subtype C infected patients in Botswana after failure of thymidine analogue-based regimens. The most frequent PI mutations involving resistance to NFV were L90M (25.2%) and D30N (16.2%), but mutations at positions K45Q and D30N were often observed in tandem (P = 60.5, J = 50; p = 0.002; Group 2) alongside Q61E in 42.8% of patients who received ZDV/3TC. 2009 Journal of the International AIDS Society Abstract HIV D30N;D30N;K45Q;L90M;Q61E 81;131;122;64;215 85;135;126;68;219 PI 18 20 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. ASP detected therapy-acquired K103N at low levels up to 6 years after cessation of NNRTI therapy. 2009 Journal of medical virology Abstract HIV K103N 30 35 NNRTI 83 88 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. ASP identified all samples that were K103N by CSA (10.5%) and an additional 14% by ASP only, representing patients who were therapy naive and with NNRTI treatment history. 2009 Journal of medical virology Abstract HIV K103N 37 42 NNRTI 147 152 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. Efavirenz (EFV) combination therapy in three patients with low-level K103N suppressed successfully viral load, although one patient developed failure and CSA-detectable K103N after 15 months of therapy. 2009 Journal of medical virology Abstract HIV K103N;K103N 69;169 74;174 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. HIV RNA was extracted from patient plasma and subjected to PCR amplification of the reverse transcriptase (RT) region followed by genotyping by CSA and real-time ASP for K103N. 2009 Journal of medical virology Abstract HIV K103N 170 175 RT;RT 84;107 105;109 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. In three patients with new HIV diagnosis and K103N detected by ASP only, K103N virus declined rapidly from the circulation but persisted in PBMC DNA at >12 months post-diagnosis. 2009 Journal of medical virology Abstract HIV K103N;K103N 45;73 50;78 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. Low-level drug resistance is not detected by routine consensus sequence genotype analysis (CSA) but low levels of specific mutations, such as the non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutation K103N, can be quantitated by allele-specific PCR (ASP). 2009 Journal of medical virology Abstract HIV K103N 220 225 NNRTI;NNRTI 146;194 182;199 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. This study has applied an ASP to quantitate low-level K103N in patients presenting for clinical HIV genotyping and assess the correlation with antiretroviral treatment history and outcomes. 2009 Journal of medical virology Abstract HIV K103N 54 59 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. Thus, analysis of K103N by ASP in conjunction with CSA genotyping provides additional information that reflects K103N transmission and persistence but detection of low-level K103N does not preclude successful EFV-containing combination therapy. 2009 Journal of medical virology Abstract HIV K103N;K103N;K103N 18;112;174 23;117;179 19856473 Application of an allele-specific PCR to clinical HIV genotyping samples detects additional K103N mutations in both therapy naive and experienced patients. When applied to samples from patients presenting for genotyping, the ASP detects K103N, not K103 nor K103R, but cross-reacts with K103S. 2009 Journal of medical virology Abstract HIV K103N;K103R;K103S 81;101;130 86;106;135 19864933 Development of a didanosine genotypic resistance interpretation system based on large derivation and validation datasets. RESULTS: The ddI resistance mutations and their resistance scores based on the derivation set were as follows: M41L (score of 14), T69D (24), D123S (40), T139M (54), I180V (53), M184V (-12), V189I (55), Q207K (37), L210W (25), and T215Y (eight). 2010 AIDS (London, England) Abstract HIV D123S;I180V;L210W;M184V;M41L;Q207K;T139M;T215Y;T69D;V189I 142;166;215;178;111;203;154;231;131;191 147;171;220;183;115;208;159;236;135;196 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Etravirine is active against HIV with single mutations in the reverse transcriptase (e.g., K103N) that confer class resistance to first-generation NNRTIs. 2008 Future HIV therapy Abstract HIV K103N 91 96 RT;NNRTI 62;147 83;153 19886834 Low prevalence of HIV type 1 drug resistance mutations in untreated, recently infected patients from Burkina Faso, Cote d'Ivoire, Senegal, Thailand, and Vietnam: the ANRS 12134 study. Of the 266 RT and PR sequences analyzed, two from Vietnam harbored virus with major drug resistance mutations (G190A in RT for one individual and M46I in PR for the second individual). 2009 AIDS research and human retroviruses Abstract HIV G190A;M46I 111;146 117;150 PR;PR;RT;RT 18;154;11;120 20;156;13;122 19886836 Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention. M184V was not detected. 2009 AIDS research and human retroviruses Abstract HIV M184V 0 5 19886836 Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention. Only two (1%) specimens had detectable K65R by OLA. 2009 AIDS research and human retroviruses Abstract HIV K65R 39 43 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Additionally, the emergence and prevalence of V75L indicates that this mutation may provide the virus a selective advantage, perhaps escaping the host immure system surveillance. 2009 Retrovirology Abstract HIV V75L 46 50 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Eventually, all subpopulations from these two macaques carried the V75L mutation. 2009 Retrovirology Abstract HIV V75L 67 71 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. However, during ART, virus subpopulations containing resistance mutations did not outgrow the wide-type subpopulations until a minor subpopulation carrying linked drug resistance mutations (K103N/M184I) emerged. 2009 Retrovirology Abstract HIV K103N;M184I 190;196 195;201 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. We also found that subpopulations carrying the V75L mutation, not known to be associated with NNRTI resistance, emerged initially in week 13 in two macaques. 2009 Retrovirology Abstract HIV V75L 47 51 NNRTI 94 99 19889767 A single amino acid substitution in HIV-1 reverse transcriptase significantly reduces virion release. We previously showed that a Gag-Pol deletion mutation involving the reverse transcriptase tryptophan (Trp) repeat motif markedly impairs PR-mediated virus maturation and that an alanine substitution at W401 (W401A) or at both W401 and W402 (W401A/W402A) partially or almost completely negates the enhancement effect of efavirenz (a nonnucleoside reverse transcriptase inhibitor) on PR-mediated virus processing efficiency. 2010 Journal of virology Abstract HIV W401A;W401A;W402A 208;241;247 213;246;252 NNRTI;RT;GagPol;PR;PR 332;68;28;137;382 367;89;35;139;384 19890215 CYP2C19 genetic variants affect nelfinavir pharmacokinetics and virologic response in HIV-1-infected children receiving highly active antiretroviral therapy. A multivariate analysis demonstrated that age (P = 0.03), concomitant protease inhibitor use (P < 0.001), and the CYP2C19-G681A genotype (P < 0.001) remained significant covariates associated with nelfinavir CL/F. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G681A 122 127 PR 70 78 19890215 CYP2C19 genetic variants affect nelfinavir pharmacokinetics and virologic response in HIV-1-infected children receiving highly active antiretroviral therapy. Furthermore, the CYP2C19-G681A genotype was related to virologic responses at week 24 (P = 0.01). 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G681A 25 30 19890215 CYP2C19 genetic variants affect nelfinavir pharmacokinetics and virologic response in HIV-1-infected children receiving highly active antiretroviral therapy. RESULTS: Nelfinavir CL/F and M8 to nelfinavir ratios were significantly associated with the CYP2C19-G681A genotypes (P < 0.001). 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G681A 100 105 19895208 Antiretroviral drug-resistant mutations at baseline and at time of failure of antiretroviral therapy in HIV type 1-coinfected TB patients. Among NRTI mutations, M184V was the commonest followed by L74I/V. 2009 AIDS research and human retroviruses Abstract HIV L74I;L74V;M184V 58;58;22 64;64;27 NRTI 6 10 19895208 Antiretroviral drug-resistant mutations at baseline and at time of failure of antiretroviral therapy in HIV type 1-coinfected TB patients. At baseline, major DRMs with respect to NNRTIs (G190GA) and TAMs (T215S and I) were observed in 3 out of 107 patients. 2009 AIDS research and human retroviruses Abstract HIV G190A;G190G;T215S 48;48;66 54;54;72 NNRTI 40 46 19895208 Antiretroviral drug-resistant mutations at baseline and at time of failure of antiretroviral therapy in HIV type 1-coinfected TB patients. V106M was the major NNRTI mutation that emerged in EFZ and Y181C in the NVP group. 2009 AIDS research and human retroviruses Abstract HIV Y181C;V106M 59;0 64;5 NNRTI 20 25 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. (1)H-(15)N NMR correlation spectra revealed that PR(G86A) and PR(G86S) are dimeric, exhibiting dimer dissociation constants (K(d)) of approximately 0.5 and approximately 3.2 muM, respectively, which are significantly lower than that seen for PR with R87K mutation (K(d) > 1 mM). 2010 Proteins Abstract HIV G86A;G86S;R87K 52;65;250 56;69;254 PR;PR;PR 49;62;242 51;64;244 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. Both NMR chemical shift data and crystal structures of PR(G86A) and PR(G86S) in the presence of active-site inhibitors indicated high structural similarity to previously described PR/inhibitor complexes, except for specific perturbations within the active site loop and around the mutation site. 2010 Proteins Abstract HIV G86A;G86S 58;71 62;75 PR;PR;PR 55;68;180 57;70;182 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. The structural and functional role of conserved residue G86 in HIV-1 protease (PR) was investigated by NMR and crystallographic analyses of substitution mutations of glycine to alanine and serine (PR(G86A) and PR(G86S)). 2010 Proteins Abstract HIV G86A;G86S 200;213 204;217 PR;PR;PR;PR 69;79;197;210 77;81;199;212 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. While PR(G86S) had undetectable catalytic activity, PR(G86A) exhibited approximately 6000-fold lower catalytic activity than PR. 2010 Proteins Abstract HIV G86A;G86S 55;9 59;13 PR;PR;PR 6;52;125 8;54;127 19901095 Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. A molecular modeling study confirmed that Y143R/C mutations play a role similar to that determined for Q148R/H mutations. 2010 Antimicrobial agents and chemotherapy Abstract HIV Q148H;Q148R;Y143C;Y143R 103;103;42;42 110;110;49;49 19901095 Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. Furthermore, the 50% effective concentration (EC(50)) determined for Y143R/C mutants was significantly higher than that obtained with G140S/Q148R mutants. 2010 Antimicrobial agents and chemotherapy Abstract HIV G140S;Q148R;Y143C;Y143R 134;140;69;69 139;145;76;76 19901095 Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. However, Y143R/C activity can be kinetically restored, thereby reproducing the effect of the secondary G140S mutation that rescues the defect associated with the Q148R/H mutants. 2010 Antimicrobial agents and chemotherapy Abstract HIV G140S;Q148H;Q148R;Y143C;Y143R 103;162;162;9;9 108;169;169;16;16 19901095 Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. Our observations demonstrate that Y143R/C mutants are strongly impaired for both of these activities in vitro. 2010 Antimicrobial agents and chemotherapy Abstract HIV Y143C;Y143R 34;34 41;41 19901095 Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. The aims of this study were to investigate the susceptibility of HIV-1 Y143R/C mutants to raltegravir and to determine the effects of these mutations on the IN-mediated reactions. 2010 Antimicrobial agents and chemotherapy Abstract HIV Y143R 71 78 IN 157 159 19901096 Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients. Factors independently associated with a better VR to ETR were the number of drugs (among enfuvirtide, darunavir, or raltegravir) used for the first time in combination with ETR and the presence of the K103N mutation at baseline. 2010 Antimicrobial agents and chemotherapy Abstract HIV K103N 201 206 19901096 Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients. Mutations Y181V and E138A were independently associated with poor VR, whereas no effect of the Y181C on VR was observed. 2010 Antimicrobial agents and chemotherapy Abstract HIV E138A;Y181C;Y181V 20;95;10 25;100;15 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. Five of the seven peptides that bound to A*0301 contained the K403R mutation and corresponded to the documented LARNCRAPRK-A3 supertype epitope. 2010 Journal of immunological methods Abstract HIV K403R 62 67 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. Two epitope variants, RASVLSGGK and RASILSGGK containing the V7I mutation, were identified using the iTopia Epitope Discovery System, however only the consensus variant (RAK9C) was confirmed using the ELISpot assay and it represents a novel A*0301 epitope. 2010 Journal of immunological methods Abstract HIV V7I 61 64 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. Using this approach we identified/confirmed the predicted HLA-A*0301 epitopes in two regions of gag containing PS mutations V7I and K403R, one previously reported and the other novel. 2010 Journal of immunological methods Abstract HIV K403R;V7I 132;124 137;127 Gag 96 99 19906925 Identification of the cellular prohibitin 1/prohibitin 2 heterodimer as an interaction partner of the C-terminal cytoplasmic domain of the HIV-1 glycoprotein. Strong binding was dependent on Env residues 790 to 800 and could be severely inhibited by the double mutation L799R/L800Q but not by mutation of these amino acids individually. 2010 Journal of virology Abstract HIV L799R;L800Q 111;117 116;122 Env 32 35 19906925 Identification of the cellular prohibitin 1/prohibitin 2 heterodimer as an interaction partner of the C-terminal cytoplasmic domain of the HIV-1 glycoprotein. Thus, mutated virions with single mutations [HIV-Env-(L799R) and HIV-Env-(L800Q)] replicated similarly to wild-type HIV, but HIV-Env-(L799R/L800Q) virions, which cannot bind Phb1/Phb2, exhibited a cell-dependent replicative phenotype similar to that of HIV-Env-Tr712, lacking the entire Env-CT domain. 2010 Journal of virology Abstract HIV L799R;L799R;L800Q;L800Q 134;54;140;74 139;59;145;79 Env;Env;Env;Env;Env 49;69;129;257;287 52;72;132;260;290 19910081 Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations. Enthalpic and entropic balance is analyzed to explain resistance in I50V and V82A having a higher entropic contribution than in the wild type (WT) complex. 2010 European journal of medicinal chemistry Abstract HIV I50V;V82A 68;77 72;81 19910081 Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations. Our results show I50V and V82A have larger structural changes than I84V compared with WT. 2010 European journal of medicinal chemistry Abstract HIV I50V;I84V;V82A 17;67;26 21;71;30 19910081 Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations. The reduced van der Waals energy explains the drug resistance of I84V to GRL-98065. 2010 European journal of medicinal chemistry Abstract HIV I84V 65 69 19910081 Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations. The single mutations I50V, V82A and I84V are considered as the key residue mutations of the HIV-1 protease drug resistance. 2010 European journal of medicinal chemistry Abstract HIV I50V;I84V;V82A 21;36;27 25;40;31 PR 98 106 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. At identification of viremia, 45 (66%) of 68 patients had HIV-1 drug resistance, 42 (62%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 25 (37%) had M184V/I, and 4 (6%) had multi-nucleoside analogue drug mutations. 2009 Clinical infectious diseases Abstract HIV M184I;M184V 173;173 180;180 NNRTI;NNRTI 94;141 129;146 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. By 12 months of persistent viremia among a subset of 14 patients with resistance testing to 12 months, 11 (78%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 8 (57%) had M184V/I, and 2 (14%) had multi-nucleoside analogue drug mutations. 2009 Clinical infectious diseases Abstract HIV M184I;M184V 194;194 201;201 NNRTI;NNRTI 116;163 151;168 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Dual versus triple PLAT and prolonged zidovudine exposure were associated with selection of M184V. 2010 AIDS (London, England) Abstract HIV M184V 92 97 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. In women receiving dual or triple PLAT, respectively, postpartum M184V/I rates were 65% (95% by ASPCR) and 28.7% (51.6% by ASPCR), respectively (P < 0.01). 2010 AIDS (London, England) Abstract HIV M184I;M184V 65;65 72;72 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Nevirapine use and length of zidovudine and lamivudine exposure were associated with selection of K103N. 2010 AIDS (London, England) Abstract HIV K103N 98 103 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Postpartum drug resistance mutation rates were assessed blindly using population sequencing and allele-specific PCR (ASPCR) of the M184V, K103N and D30N mutations. 2010 AIDS (London, England) Abstract HIV D30N;K103N;M184V 148;138;131 152;143;136 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Postpartum nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance rates among women receiving nevirapine were 25% for K103N (37.5% by ASPCR) and 12.5% for Y188C. 2010 AIDS (London, England) Abstract HIV K103N;Y188C 128;165 133;170 NNRTI;NNRTI 11;58 46;63 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Protease inhibitor resistance rates in women receiving nelfinavir were 1.1% for D30N (1.1% by ASPCR) and 1.1% for L90M. 2010 AIDS (London, England) Abstract HIV D30N;L90M 80;114 84;118 PR 0 8 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Triple-drug PLAT decreases the odds for M184V selection. 2010 AIDS (London, England) Abstract HIV M184V 40 45 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. The common polymorphism T125A, which was characteristic of non-subtype B and was also associated with carriage of HLA-B*57/*5801, increased the mutational barrier to the resistance mutation T125K. 2009 Antiviral therapy Abstract HIV T125A;T125K 24;190 29;195 19918103 The incidence rate of HIV type-1 drug resistance in patients on antiretroviral therapy: a nationwide population-based Danish cohort study 1999-2005. The IRs were low for specific resistance mutations, except for M184V (IR 5.6 [4.0-7.9]) and K103N (IR 8.2 [5.6-12.0]). 2009 Antiviral therapy Abstract HIV K103N;M184V 92;63 97;68 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. M184V (80% versus 75%), thymidine analogue mutations (63% versus 74%), Y181C (39% versus 39%) and K103N (29% versus 39%) were predominant RT mutations in both groups. 2009 Antiviral therapy Abstract HIV K103N;Y181C;M184V 98;71;0 103;76;5 RT 138 140 19918107 Progress in basic and clinical research on HIV resistance: report on the XVIII International HIV Drug Resistance Workshop. The XVIII workshop featured work on HIV type-1 (HIV-1) persistence, reservoirs and elimination strategies; resistance to HIV-1 entry inhibitors (including a comparison of genotyping versus phenotyping to determine HIV-1 coreceptor use before treatment with CCR5 antagonists); polymerase domain resistance to reverse transcriptase inhibitors (including hepatitis B virus and HIV-1 resistance to lamivudine, and emergence of the K65R mutation in HIV-1 subtypes B and C); connection and RNase H domain resistance to reverse transcriptase inhibitors (including the effect of mutations in those domains on response to efavirenz and etravirine); resistance to hepatitis C virus and HIV-1 protease inhibitors; resistance to the integrase inhibitor raltegravir; global resistance epidemiology (including models to predict response to second-line antiretrovirals in resource-poor settings); and the role of minority resistant variants (including the effect of such variants on prevention of mother-to-child transmission of HIV-1). 2009 Antiviral therapy Abstract HIV K65R 427 431 RT;RT;Pol;IN;PR 308;513;276;721;682 329;534;286;730;690 19919951 Impact of reduced dosing of lopinavir/ritonavir in virologically controlled HIV-infected patients: the Kaledose trial. In the 15 patients with transient viraemia, analysis of proviral DNA for antiretroviral resistance showed that mutations had occurred when compared with baseline genotypes in three patients: I47M (n = 2) and M46I (n = 1). 2010 The Journal of antimicrobial chemotherapy Abstract HIV I47M;M46I 191;208 195;212 19921401 Impact of template overhang-binding region of HIV-1 RT on the binding and orientation of the duplex region of the template-primer. The E-TP covalent complexes from W24F mutant displayed wild-type activity while those from W24A, F61A, F61Y, and the double mutant (W24A/F61A) were significantly impaired in their ability to catalyze dNTP incorporation onto the immobilized primer terminus. 2010 Molecular and cellular biochemistry Abstract HIV F61A;F61A;F61Y;W24A;W24A;W24F 97;137;103;91;132;33 101;141;107;95;136;37 19921401 Impact of template overhang-binding region of HIV-1 RT on the binding and orientation of the duplex region of the template-primer. Using a specially designed template-primer with photoactivatable bromo-dU base in the duplex region at the penultimate position to the primer terminus, we demonstrated that F61A, W24A, F61Y as well as the double mutant were also affected in their cross-linking ability with the duplex region of the template-primer. 2010 Molecular and cellular biochemistry Abstract HIV F61A;F61Y;W24A 173;185;179 177;189;183 19921401 Impact of template overhang-binding region of HIV-1 RT on the binding and orientation of the duplex region of the template-primer. We noted that W24A, F61A, and F61Y and the double mutant (W24A/F61A) were significantly affected in their ability to bind template-primer and also to catalyze the polymerase reaction while W24F remained unaffected. 2010 Molecular and cellular biochemistry Abstract HIV F61A;F61A;F61Y;W24A;W24A;W24F 20;63;30;14;58;189 24;67;34;18;62;193 Pol 163 173 19926360 Design and synthesis of novel P2 substituents in diol-based HIV protease inhibitors. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M46I, V82F, and I84V mutations. 2010 European journal of medicinal chemistry Abstract HIV I84V;M46I;V82F 114;98;104 118;102;108 PR 49 57 19926962 High prevalence of bevirimat resistance mutations in protease inhibitor-resistant HIV isolates. Accumulation of mutations at four positions in the bevirimat target region, S368C, Q369H, V370A and S373P, was significantly observed. 2010 AIDS (London, England) Abstract HIV Q369H;S368C;S373P;V370A 83;76;100;90 88;81;105;95 19926962 High prevalence of bevirimat resistance mutations in protease inhibitor-resistant HIV isolates. RESULTS: In the treatment-naive patient population, approximately 30% harboured an HIV isolate with at least one mutation associated with a reduced susceptibility to bevirimat (H358Y, L363M, Q369H, V370A/M/del and T371del). 2010 AIDS (London, England) Abstract HIV H358Y;L363M;Q369H;T371del;V370A;V370M 177;184;191;214;198;198 182;189;196;221;205;205 19933171 Level of viral load and antiretroviral resistance after 6 months of non-nucleoside reverse transcriptase inhibitor first-line treatment in HIV-1-infected children in Mali. Among the children with detectable VL, 30/37 genotypic resistance tests were available, 8 with wild-type viruses and 22 with resistance mutations (73%): 19 M184V/I, 21 NNRTI mutations and only 3 thymidine analogue mutations (TAMs) (K70R, D67N and L210W in three distinct viruses). 2010 The Journal of antimicrobial chemotherapy Abstract HIV M184V;D67N;K70R;L210W 156;238;232;247 163;242;236;252 NNRTI 168 173 19933797 TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. E138R was identified as a new NNRTI RAM. 2010 Antimicrobial agents and chemotherapy Abstract HIV E138R 0 5 NNRTI 30 35 19933797 TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. NNRTI RAMs emerging in HIV-1 under selective pressure from TMC278 included combinations of V90I, L100I, K101E, V106A/I, V108I, E138G/K/Q/R, V179F/I, Y181C/I, V189I, G190E, H221Y, F227C, and M230I/L. 2010 Antimicrobial agents and chemotherapy Abstract HIV E138G;E138K;E138Q;E138R;F227C;G190E;H221Y;K101E;L100I;M230I;M230L;V106A;V106I;V108I;V179F;V179I;V189I;V90I;Y181C;Y181I 127;127;127;127;179;165;172;104;97;190;190;111;111;120;140;140;158;91;149;149 138;138;138;138;184;170;177;109;102;197;197;118;118;125;147;147;163;95;156;156 NNRTI 0 5 19933797 TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. The HIV-1 site-directed mutant with Y181C was sensitive to TMC278, whereas that with K101P or Y181I/V was resistant. 2010 Antimicrobial agents and chemotherapy Abstract HIV K101P;Y181C;Y181I;Y181V 85;36;94;94 90;41;101;101 19935274 Emergence of drug resistance in HIV-1 subtype C infected children failing the South African national antiretroviral roll-out program. Ninety-eight percent presented with known drug resistance mutations with M184V (82%) and K103N (44%), the dominant mutations. 2009 The Pediatric infectious disease journal Abstract HIV K103N;M184V 89;73 94;78 19938977 Viral rebound and emergence of drug resistance in the absence of viral load testing: a randomized comparison between zidovudine-lamivudine plus Nevirapine and zidovudine-lamivudine plus Abacavir. The mean residual activity at week 48 was higher for abacavir in the presence of the typically observed resistance pattern of thymidine analogue mutations (TAMs) and M184V (1.47 log(10) copies/mL) than for nevirapine with M184V and nonnucleoside reverse-transcriptase inhibitor mutations, whether accompanied by TAMs (0.96 log(10) copies/mL) or not (1.18 log(10) copies/mL). 2010 The Journal of infectious diseases Abstract HIV M184V;M184V 166;222 171;227 NNRTI 232 267 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Co-immunoprecipitation analysis revealed that L63A and V68A mutants were capable of binding CD4 and still retained the ability to interact with h-beta-TrCP1. 2010 Virology Abstract HIV L63A;V68A 46;55 50;59 19949656 Antiretroviral genotypic resistance mutations in HIV-1 infected Korean patients with virologic failure. M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (41.5%) and M46I/L (34%). 2009 Journal of Korean medical science Abstract HIV M184I;M184V;M46I;M46L;T215F;T215Y 0;0;85;85;65;65 7;7;91;91;72;72 19950236 Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens. In two patients with raltegravir resistance, the simultaneous appearance of additional mutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. 2010 Journal of medical virology Abstract HIV E170A;Y143R 108;98 113;104 IN 177 186 19950236 Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens. Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1 month after initiating salvage HAART. 2010 Journal of medical virology Abstract HIV E92G;G140S;N155H;Q148H 59;65;83;72 63;70;88;77 19951947 Determinants for the rhesus monkey TRIM5alpha-mediated block of the late phase of HIV-1 replication. Intriguingly, TRIM5alpharh coiled-coil domain mutants (M133T and/or T146A) showed impaired late restriction activity, despite the efficient encapsidation and cytoplasmic body formation. 2010 The Journal of biological chemistry Abstract HIV M133T;T146A 55;68 61;73 19954302 HIV type 1 subtype diversity and drug resistance among HIV type 1-infected Kenyan patients initiating antiretroviral therapy. Nonnucleoside RTI resistance-associated mutations K103N and Y181C were detected in three patients and one patient, respectively. 2009 AIDS research and human retroviruses Abstract HIV K103N;Y181C 50;60 55;65 RT 14 17 19954302 HIV type 1 subtype diversity and drug resistance among HIV type 1-infected Kenyan patients initiating antiretroviral therapy. Of these patients, three had nucleoside RTI resistance mutations, such as M184V, K65R, D67N, K70R, and K219Q. 2009 AIDS research and human retroviruses Abstract HIV D67N;K219Q;K65R;K70R;M184V 87;103;81;93;74 91;108;85;97;79 RT 40 43 19959414 The use of integrase inhibitors in treatment-experienced patients. Tolerance was remarkably good and virological failure was often associated with selection of integrase gene resistance mutations following the Y143C/H/R, Q148H/K/R o less frequently the NI55H paths. 2009 European journal of medical research Abstract HIV Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 154;154;154;143;143;143 163;163;163;152;152;152 IN 93 102 19959417 HIV resistance to raltegravir. HIV resistance to raltegravir is the consequence of mutations located close to the integrase active site, which can be divided into three main evolutionary pathways: the N155H, the Q148R/H/K and the Y143R/C pathways. 2009 European journal of medical research Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 170;181;181;181;199;199 175;190;190;190;206;206 IN 83 92 19959417 HIV resistance to raltegravir. Resistance is frequently initiated by viruses carrying mutations of the N155H pathway, followed by emergence and further dominance of viral genomes carrying mutations of the Q148R/H/K or of the Y143R/C pathways, which express higher levels of resistance. 2009 European journal of medical research Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 72;174;174;174;194;194 77;183;183;183;201;201 19961222 HIV-1 protease inhibitors with a transition-state mimic comprising a tertiary alcohol: improved antiviral activity in cells. The synthesis of 25 new and optically pure HIV-1 protease inhibitors is reported, along with methods for elongation of the inhibitor P1' side chain using microwave-accelerated, palladium-catalyzed cross-coupling reactions, the biological evaluation, and X-ray data obtained from one of the most potent analogues cocrystallized with both the wild type and the L63P, V82T, I84 V mutant of the HIV-1 protease. 2010 Journal of medicinal chemistry Abstract HIV I84V;L63P;V82T 371;359;365 376;363;369 PR;PR 49;397 57;405 19995921 Development of an allele-specific PCR for detection of the K65R resistance mutation in patients infected with subtype C human immunodeficiency virus type 1. Thirty HIV-1 subtype C- and 26 subtype B-infected patients lacking K65R as determined by conventional sequencing methods were studied, and viral minority species were found in four HIV-1 subtype C samples. 2010 Antimicrobial agents and chemotherapy Abstract HIV K65R 67 71 19995921 Development of an allele-specific PCR for detection of the K65R resistance mutation in patients infected with subtype C human immunodeficiency virus type 1. We have developed an allele-specific real-time PCR assay to explore the presence of K65R minority species among treated HIV-1 subtype B and C infections. 2010 Antimicrobial agents and chemotherapy Abstract HIV K65R 84 88 19996935 High prevalence of natural polymorphisms in Gag (CA-SP1) associated with reduced response to Bevirimat, an HIV-1 maturation inhibitor. Mutations H358Y, L363F/M, A364V and A366T/V confer in-vitro resistance to bevirimat. 2010 AIDS (London, England) Abstract HIV A364V;A366T;A366V;H358Y;L363F;L363M 26;36;36;10;17;17 31;43;43;15;24;24 20007331 Integrase variability and susceptibility to HIV integrase inhibitors: impact of subtypes, antiretroviral experience and duration of HIV infection. The most prevalent INI resistance-associated mutations were V72I (63.9%), V201I (54.8%), T206S (25.4%), I203M (9.8%) and K156N (7.4%). 2010 The Journal of antimicrobial chemotherapy Abstract HIV I203M;K156N;T206S;V201I;V72I 104;121;89;74;60 109;126;94;79;64 IN 19 22 20007333 Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. 2010 The Journal of antimicrobial chemotherapy Abstract HIV M184V 108 113 NRTI 86 90 HIV infections 57 71 20007333 Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. 2010 The Journal of antimicrobial chemotherapy Abstract HIV L74V;M184V 268;184 272;189 RT;NRTI 113;167 134;172 20007333 Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. In particular, the activity of apricitabine in the presence of the M184V mutation, which confers high-level resistance to lamivudine and emtricitabine, lends it to being used as a replacement for deoxycytidine analogues in patients who have failed treatment with lamivudine or emtricitabine. 2010 The Journal of antimicrobial chemotherapy Abstract HIV M184V 67 72 20008779 Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naive patients infected with non-B HIV-1 subtypes. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility. 2010 Antimicrobial agents and chemotherapy Abstract HIV Y181C 57 62 20008779 Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naive patients infected with non-B HIV-1 subtypes. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). 2010 Antimicrobial agents and chemotherapy Abstract HIV A98G;V90I;V90I;Y181C 223;183;214;192 227;188;218;197 20008779 Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naive patients infected with non-B HIV-1 subtypes. Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. 2010 Antimicrobial agents and chemotherapy Abstract HIV E138A;H221Y;V179I;V90I;Y181C;Y181C 29;56;39;67;46;76 35;61;44;71;51;81 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Both PG and CG data suggest TAMs, not K65R selection, are the preferred resistance route, biased towards 215F selection. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K65R 38 42 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. By CG at VF, for subjects with TAMs, T215F was more commonly detected (5/14 samples) than T215Y (2/14). 2010 The Journal of antimicrobial chemotherapy Abstract HIV T215F;T215Y 37;90 42;95 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. By PG at VF, 10/14 had selected for resistance mutations [2, K65R; 1, M184V; and 7, thymidine analogue mutations (TAMs) +/- M184V]. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184V;M184V 61;70;124 65;75;129 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. For one subject who selected K65R at VF, both K65R-containing clones and TAM-containing clones (both T215A and T215F) were observed independently but not conjunctively in the same clone in a post-VF sample. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K65R;K65R;T215A;T215F 29;46;101;111 33;50;106;116 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. No HIV clone contained both K65R and T215F/Y mutations, suggesting in vivo antagonism between the two mutations. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K65R;T215F;T215Y 28;37;37 32;44;44 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. Compared to the subtype B consensus, six additional polymorphisms (I13 V, E35D, M36I, R41K, H69K, L89M) were identified in the CRF01_AE consensus; all but L89M were located within epitopes recognized by HLA class I alleles. 2010 AIDS (London, England) Abstract HIV E35D;H69K;I13V;L89M;L89M;M36I;R41K 74;92;67;98;155;80;86 78;96;72;102;159;84;90 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. CONCLUSION: Polymorphisms in CRF01_AE protease gene were common, and polymorphisms at residues 10, 20 and 62 most likely represent selection by use of protease inhibitors, whereas R41K and H69K were more likely attributable to recognition of epitopes by the HLA haplotypes of the host population. 2010 AIDS (London, England) Abstract HIV H69K;R41K 189;180 193;184 PR;PR 38;151 46;159 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. Three polymorphisms (L10 V, K20RMI and I62 V) were associated with the presence of a major PRAM (P < 0.05). 2010 AIDS (London, England) Abstract HIV I62V;K20I;K20M;K20R;L10V 39;28;28;28;21 44;34;34;34;26 20009920 Sensitivity of V75I HIV-1 reverse transcriptase mutant selected in vitro by acyclovir to anti-HIV drugs. We show that the V75I variant has decreased sensitivity to some nucleoside analogs but an increased sensitivity to zidovudine, results that may guide selection of highly active antiretroviral therapy regimens in patients harboring this variant. 2010 AIDS (London, England) Abstract HIV V75I 17 21 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. However, both of these inhibitors are currently infrequently used in developed countries, and the impact of N348I on newer reverse transcriptase inhibitors, such as tenofovir and etravirine, is unknown. 2010 AIDS (London, England) Abstract HIV N348I 108 113 RT 123 144 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. However, N348I significantly decreases tenofovir susceptibility when combined with thymidine analogue mutations and etravirine susceptibility when combined with Y181C. 2010 AIDS (London, England) Abstract HIV N348I;Y181C 9;161 14;166 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. In this study, we demonstrate that N348I alone confers no resistance to tenofovir and low-level resistance to etravirine. 2010 AIDS (London, England) Abstract HIV N348I 35 40 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. We previously demonstrated that N348I in HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. 2010 AIDS (London, England) Abstract HIV N348I 32 37 RT 47 68 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. METHODS: A prospective study was conducted among HIV-infected patients who failed NNRTI-based antiretroviral therapy with M184V, TAMs, and NNRTI mutations, and were naive to protease inhibitor. 2009 AIDS research and therapy Abstract HIV M184V 122 127 NNRTI;NNRTI;PR 82;139;174 87;144;182 HIV infections 49 61 20032547 Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina. BACKGROUND: The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART). 2009 Antiviral therapy Abstract HIV K103N;M184V 118;128 123;133 20032547 Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina. CONCLUSIONS: It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. 2009 Antiviral therapy Abstract HIV M184V 47 52 20032547 Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina. No K103N minority populations were found. 2009 Antiviral therapy Abstract HIV K103N 3 8 20032547 Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01). 2009 Antiviral therapy Abstract HIV M184V 44 49 20032547 Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. 2009 Antiviral therapy Abstract HIV M184V 49 54 20038617 Lack of pharmacokinetic interaction between amdoxovir and reduced- and standard-dose zidovudine in HIV-1-infected individuals. Amdoxovir (AMDX) inhibits HIV-1 containing the M184V/I mutation and is rapidly absorbed and deaminated to its active metabolite, beta-D-dioxolane guanosine (DXG). 2010 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V 47;47 54;54 20042499 Effect of mutations in the human immunodeficiency virus type 1 protease on cleavage of the gp41 cytoplasmic tail. In the present study, we observed that a PR inhibitor-resistant (PIR) HIV-1 mutant is unable to efficiently cleave the gp41 cytoplasmic tail in P203L and S205L virions, resulting in loss of AME resistance. 2010 Journal of virology Abstract HIV P203L;S205L 144;154 149;159 gp41;PR 119;41 123;43 20042499 Effect of mutations in the human immunodeficiency virus type 1 protease on cleavage of the gp41 cytoplasmic tail. We identified a new gp41 mutation, R236L, that results in cleavage of the gp41 tail by the PIR PR. 2010 Journal of virology Abstract HIV R236L 35 40 gp41;gp41;PR 20;74;95 24;78;97 20042499 Effect of mutations in the human immunodeficiency virus type 1 protease on cleavage of the gp41 cytoplasmic tail. We previously reported that human immunodeficiency virus type 1 (HIV-1) develops resistance to the cholesterol-binding compound amphotericin B methyl ester (AME) by acquiring mutations (P203L and S205L) in the cytoplasmic tail of the transmembrane envelope glycoprotein gp41 that create cleavage sites for the viral protease (PR). 2010 Journal of virology Abstract HIV P203L;S205L 186;196 192;201 Env;PR;gp41;PR 248;316;270;326 256;324;274;328 20048718 Drugs in traditional drug classes (nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor/protease inhibitors) with activity against drug-resistant virus (tipranavir, darunavir, etravirine). Resistance to etravirine requires the accumulation of multiple reverse transcriptase mutations different from K103N, which has no impact on activity. 2009 Current opinion in HIV and AIDS Abstract HIV K103N 110 115 RT 63 84 20050672 Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile. We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC(50) = 7.4 nM, SI = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC(50) = 7.4 nM and EC(50) = 0.46 nM, respectively. 2010 Journal of medicinal chemistry Abstract HIV Y181C 325 330 20052598 Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study. An atypical protease inhibitor mutation, I47M, appeared at a resistance-associated position in protease from a single specimen. 2010 Archives of virology Abstract HIV I47M 41 45 PR;PR 12;95 20;103 20052598 Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study. Mutations were restricted to RT, with D67DG and V75AV each seen in a single specimen. 2010 Archives of virology Abstract HIV D67D;D67G;V75A;V75V 38;38;48;48 43;43;53;53 RT 29 31 20054099 Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. BACKGROUND: We have shown that the K65R resistance mutation in HIV type-1 (HIV-1) reverse transcriptase (RT) is selected more rapidly in subtype C than subtype B HIV-1 in biochemical, cell culture and clinical studies. 2010 Antiviral chemistry & chemotherapy Abstract HIV K65R 35 39 RT;RT 82;105 103;107 20054099 Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. CONCLUSIONS: These results further establish a mechanistic basis for the exclusion of both K65R and TAMs on single templates as well as the preferential acquisition of K65R in subtype C viruses. 2010 Antiviral chemistry & chemotherapy Abstract HIV K65R;K65R 91;168 95;172 20054099 Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. Template-usage experiments demonstrated that subtype C nucleotide coding sequences caused RT to preferentially pause, leading to K65R acquisition. 2010 Antiviral chemistry & chemotherapy Abstract HIV K65R 129 133 RT 90 92 20054099 Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. This new study now further establishes the basis for differential occurrence of both K65R and thymidine analogue mutations (TAMs) between subtypes. 2010 Antiviral chemistry & chemotherapy Abstract HIV K65R 85 89 20055526 Structural and energetic analysis on the complexes of clinically isolated subtype C HIV-1 proteases and approved inhibitors by molecular dynamics simulation. The effect of the V82I mutation on the association with chemicals and the reason for rare appearance of the D30N mutation in subtype C HIV-1 were discussed in terms of the change of geometry of the residues in HIV-1 protease. 2010 The journal of physical chemistry. B Abstract HIV D30N;V82I 108;18 112;22 PR 216 224 20055586 Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41 heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*). However, viruses with the V38M + N43T-N44K mutations were not infectious and, as shown by Western blotting, gPr160 cleavage was impaired. 2010 AIDS research and human retroviruses Abstract HIV N43T;N44K;V38M 33;38;26 37;42;30 20055586 Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41 heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*). These data may explain why viruses with V38M + N43T-N44K mutations were not previously detected in the plasma of T-20-experienced patients. 2010 AIDS research and human retroviruses Abstract HIV N43T;N44K;V38M 47;52;40 51;56;44 20055586 Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41 heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*). These data suggest that V38M + N43T-N44K mutations perturbed the natural conformation of gPr160 in a way that access of furin to the cleavage site (REKR) was blocked. 2010 AIDS research and human retroviruses Abstract HIV N43T;N44K;V38M 31;36;24 35;40;28 20055586 Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41 heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*). To address this problem, we introduced N43T-N44K and V38M + N43T-N44K substitutions to a cloned gp41 and introduced modified gp41 into the pNL4-3 molecular clone. 2010 AIDS research and human retroviruses Abstract HIV N43T;N43T;N44K;N44K;V38M 39;60;44;65;53 43;64;48;69;57 gp41;gp41 96;125 100;129 20055586 Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41 heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*). Two mutations, a single V38A and a double N43T-N44K were the most frequent; however, they were not found together in one clone. 2010 AIDS research and human retroviruses Abstract HIV N43T;N44K;V38A 42;47;24 46;51;28 20056480 Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure: a pilot randomised trial. BACKGROUND: In HIV-1-infected patients harbouring the M184V mutation (M184V), lamivudine monotherapy leads to a smaller decrease in CD4 percentages (CD4%) than treatment interruption, possibly due to the reduced fitness of the mutated virus. 2010 Journal of clinical virology Abstract HIV M184V;M184V 54;70 59;75 HIV infections 15 29 20056480 Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure: a pilot randomised trial. CONCLUSIONS: Once-weekly emtricitabine led to a higher viral rebound than once-daily monotherapy, but similar immunological changes, thus suggesting a role of M184V in slowing the decrease in CD4% in treatment failing subjects. 2010 Journal of clinical virology Abstract HIV M184V 159 164 20056480 Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure: a pilot randomised trial. M184V was maintained in all the participants. 2010 Journal of clinical virology Abstract HIV M184V 0 5 20056480 Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure: a pilot randomised trial. OBJECTIVE: We assessed whether a minimal dose of a cytidine analogue that is theoretically sufficient to maintain M184V (one emtricitabine tablet once-weekly) may be as effective. 2010 Journal of clinical virology Abstract HIV M184V 114 119 20056687 Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir. DISCUSSION: Two patterns of viral evolution were observed in the resistant viral populations, driving the variants towards a fast (most of them with G140S + Q148H mutations) or progressive increase in resistance to raltegravir. 2010 The Journal of antimicrobial chemotherapy Abstract HIV G140S;Q148H 149;157 154;162 20056687 Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir. Unlike mutations at position 143 (Y143S/K/R), identified alone or in combination with others, mutations at position 148 and 155 were always found in combination. 2010 The Journal of antimicrobial chemotherapy Abstract HIV Y143K;Y143R;Y143S 34;34;34 43;43;43 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. In summary, residues that alter the electronegative status of C3d (D163A and N170R) impair the binding of chimera proteins to CR2, reducing the adjuvant activity of this molecule. 2010 Immunology letters Abstract HIV D163A;N170R 67;77 73;82 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Mutation at residue 162 (R162A) neither enhanced nor impaired the avidity of Env(gp120)-C3d(2) for sCR2 in vitro. 2010 Immunology letters Abstract HIV R162A 25 30 gp120;Env 81;77 86;80 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Mutations at residues D163A and N170R, on the other hand, reduced the binding affinity of Env(gp120)-C3d(2) for sCR2. 2010 Immunology letters Abstract HIV D163A;N170R 22;32 27;37 gp120;Env 94;90 99;93 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Previous experiments demonstrated that elimination of a positive charge (K162A) in C3d enhanced its avidity for CR2, while elimination of negative charges or addition positives ones (D163A, N170R, respectively), impaired the avidity for CR2. 2010 Immunology letters Abstract HIV D163A;K162A;N170R 183;73;190 188;78;195 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. To study the role of residues at the interacting and non-interacting surface of C3d on the adjuvanticity, single as well as a double residue substitutions were engineered in the murine C3d (R162A, D163A, N170R and D163A-N170R) gene. 2010 Immunology letters Abstract HIV D163A;D163A;N170R;N170R;R162A 197;214;204;220;190 202;219;209;225;195 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. As a consequence, the S52A Vpu mutant virus was unable to replicate in macrophages, which express high levels of this restriction factor. 2010 Retrovirology Abstract HIV S52A 22 26 Vpu 27 30 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. CONCLUSION: Our data explain why the effect of the S52A mutation in Vpu on virus release is cell-type dependent and suggest that a reduced ability of Vpu to counteract tetherin impairs HIV-1 replication in macrophages, but not in tissue CD4+ T cells. 2010 Retrovirology Abstract HIV S52A 51 55 Vpu;Vpu 68;150 71;153 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. In contrast, HIV-1 Vpu S52A caused CD4+ T-cell depletion and spread efficiently in ex vivo human lymphoid tissue and PBL, most likely because these cells express comparably low levels of tetherin. 2010 Retrovirology Abstract HIV S52A 23 27 Vpu 19 22 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Overall, Vpu S52A could only overcome low levels of tetherin, and its activity decreased in a manner dependent on the amount of transiently or endogenously expressed tetherin. 2010 Retrovirology Abstract HIV S52A 13 17 Vpu 9 12 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. RESULTS: We show that mutation of serine 52 to alanine (S52A) entirely disrupts Vpu-mediated degradation of CD4 and strongly impairs its ability to antagonize tetherin. 2010 Retrovirology Abstract HIV S52A;S52A 56;34 60;54 Vpu 80 83 20087934 HIV-1 primary and secondary antiretroviral drug resistance and genetic diversity among pregnant women from central Brazil. Naive patients had accessory mutations in the PR gene [A71T (1/6), L10V (2/6), L10I (3/6)] and in the RT gene [V118I (2/6), V179D (1/6), V106I (1/6), K101Q (1/6), H221Y (1/6)]. 2010 Journal of medical virology Abstract HIV A71T;H221Y;K101Q;L10I;L10V;V106I;V118I;V179D 55;163;150;79;67;137;111;124 59;168;155;83;71;142;116;129 PR;RT 46;102 48;104 20096702 A dynamic model of HIV integrase inhibition and drug resistance. These models have allowed us to (1) explore the effects of key drug resistance mutations on the dynamic flexibility and conformational preferences of HIV integrase and to (2) study raltegravir binding in the context of these dynamic models of both wild type and the G140S/Q148H drug-resistant enzyme. 2010 Journal of molecular biology Abstract HIV G140S;Q148H 266;272 271;277 IN 154 163 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. CONCLUSIONS: In adherent patients, pre-existing minority Y181C mutants more than tripled the risk of virologic failure of first-line efavirenz-based antiretroviral therapy. 2010 The Journal of infectious diseases Abstract HIV Y181C 57 62 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Detection of minority Y181C mutants was associated with an increased risk of virologic failure in the setting of recent treatment adherence (hazard ratio, 3.45 [95% confidence interval, 1.90-6.26]) but not in nonadherent subjects (hazard ratio, 1.39 [95% confidence interval, 0.58-3.29]). 2010 The Journal of infectious diseases Abstract HIV Y181C 22 27 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Minority K103N or Y181C populations were determined by allele-specific polymerase chain reaction in subjects without NNRTI resistance by population sequencing. 2010 The Journal of infectious diseases Abstract HIV K103N;Y181C 9;18 14;23 Pol;NNRTI 71;117 81;122 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Of note, 70% of subjects with minority Y181C variants achieved long-term viral suppression. 2010 The Journal of infectious diseases Abstract HIV Y181C 39 44 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Presence of minority K103N or Y181C mutations, or both, was detected in 8 (4.4%), 54 (29.5%), and 11 (6%), respectively, of 183 evaluable subjects in the random subcohort. 2010 The Journal of infectious diseases Abstract HIV K103N;Y181C 21;30 26;35 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. K103N variants at frequencies 11% were associated with inferior HIV-1 RNA response to efavirenz-containing therapy between entry and week 24 (change in HIV-1 RNA level, +0.5 vs -1.1 log(10) copies/mL; P < .001). 2010 The Journal of infectious diseases Abstract HIV K103N 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. METHODS: Plasma samples at entry and at time of virologic failure from patients enrolled in the AIDS Clinical Trials Group study 398 were analyzed by standard genotype, single-genome sequencing and allele-specific polymerase chain reaction (K103N and Y181C) to detect and quantify minor NNRTI-resistant variants. 2010 The Journal of infectious diseases Abstract HIV K103N;Y181C 241;251 247;256 NNRTI;Pol 287;214 292;224 AIDS 96 100 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. RESULTS: Minor populations of NNRTI-resistant variants that were missed by standard genotype were detected more often at study entry in NNRTI-experienced patients than NNRTI-naive patients by both single-genome sequencing (8 of 12 vs 3 of 15; P = .022) and allele-specific polymerase chain reaction (11% Y181C, 5 of 22 vs 3 of 72, respectively; P = .016). 2010 The Journal of infectious diseases Abstract HIV Y181C 304 309 NNRTI;NNRTI;NNRTI;Pol 30;136;168;273 35;141;173;283 20108932 Synthesis of new thienyl ring containing HIV-1 protease inhibitors: promising preliminary pharmacological evaluation against recombinant HIV-1 proteases. The range of activity of the two most active compounds is substantially maintained or even increased against two commonly selected mutants, under drug pressure, such as V32I and V82A. 2010 Journal of medicinal chemistry Abstract HIV V32I;V82A 169;178 173;182 20112173 IDX-899, an aryl phosphinate-indole non-nucleoside reverse transcriptase inhibitor for the potential treatment of HIV infection. Two pathways of resistance have been identified for IDX-899 in vitro that include Glu138Lys and Val90Ile/Tyr181Cys mutations. 2010 Current opinion in investigational drugs (London, England Abstract HIV E138K;V90C;V90I;V90Y;Y181C 82;96;96;96;105 91;104;104;104;114 20116329 High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong. G36D was encountered most frequently and more prevalent in non-B subtypes. 2010 Journal of clinical virology Abstract HIV G36D 0 4 20116329 High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong. In three longitudinal samples from an ENF-treated patient, G36D was detected after ENF treatment for 6 months and the mutation persisted after termination of ENF for 6 months. 2010 Journal of clinical virology Abstract HIV G36D 59 63 20116329 High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong. N42S and L54M were predominant in CRF01_AE and subtype B, respectively. 2010 Journal of clinical virology Abstract HIV L54M;N42S 9;0 13;4 20116329 High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong. N42S, L54M and V69I were the major polymorphisms detected. 2010 Journal of clinical virology Abstract HIV L54M;V69I;N42S 6;15;0 10;19;4 20116329 High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong. Our findings from the ENF-treated patient showed that G36D mutation persisted as long as 6 months after ENF withdrawal. 2010 Journal of clinical virology Abstract HIV G36D 54 58 20116329 High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong. V69I was found in all samples harboring G36D. 2010 Journal of clinical virology Abstract HIV G36D;V69I 40;0 44;4 20121622 Surveillance of transmitted HIV type 1 drug resistance in newly diagnosed hiv type 1-infected patients in Shandong Province, China. Forty-six of the 47 successfully genotyped DBS had no transmitted DR mutations; one had an NNRTI mutation (K101E) in the RT region. 2010 AIDS research and human retroviruses Abstract HIV K101E 107 112 NNRTI;RT 91;121 96;123 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Early processing intermediates accumulated in p51 downward arrowRNH cleavage site mutant viruses, whereas introduction of T477A promoted the completion of processing and formation of the fully processed RT p66/p51 heterodimer. 2010 Retrovirology Abstract HIV T477A 122 127 RT 203 205 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. However, in one case, the recovered virus retained the mutated p51 downward arrowRNH cleavage site but also developed an additional mutation, T477A, distal to the cleavage site. 2010 Retrovirology Abstract HIV T477A 142 147 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In this study we have characterized in detail the impact of the T477A mutation on intravirion processing of RT. 2010 Retrovirology Abstract HIV T477A 64 69 RT 108 110 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. RESULTS: While the T477A mutation arose during serial passage only with the F440V mutant background, introduction of this substitution into a variety of RT p51 downward arrowRNH cleavage site lethal mutant backgrounds was able to restore substantial infectivity and normal RT processing to these mutants. 2010 Retrovirology Abstract HIV F440V;T477A 76;19 81;24 RT;RT 153;273 155;275 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. T477A had no phenotypic effect on wild-type HIV-1. 2010 Retrovirology Abstract HIV T477A 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The ability of T477A to restore RT heterodimer formation and thus intravirion stability of the enzyme may arise from increased conformation flexibility in the RT p51 downward arrowRNH cleavage site region, due to loss of a hydrogen bond associated with the normal threonine residue, thereby enabling proteolytic cleavage near the normal RT p51 downward arrowRNH cleavage site. 2010 Retrovirology Abstract HIV T477A 15 20 RT;RT;RT 32;159;337 34;161;339 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. We also evaluated the impact of T477A on the kinetics of intravirion Gag-Pol polyprotein processing of p51 downward arrowRNH cleavage site mutants using the protease inhibitor ritonavir. 2010 Retrovirology Abstract HIV T477A 32 37 PR;GagPol 157;69 165;76 20124001 Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. Analysis of recombinant HIV-1 clones showed that the combination of V106I and V179D conferred significant resistance to EFV and nevirapine (NVP) but not to ETV. 2010 Antimicrobial agents and chemotherapy Abstract HIV V106I;V179D 68;78 73;83 20124001 Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. Following its introduction, two naturally occurring mutations in HIV-1 RT, V106I and V179D, were listed as ETV resistance-associated mutations. 2010 Antimicrobial agents and chemotherapy Abstract HIV V106I;V179D 75;85 80;90 RT 71 73 20124001 Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. Interestingly, V179D emerged in one of three selection experiments from HIV-1(V106I) and V106I emerged in two of three experiments from HIV-1(V179D). 2010 Antimicrobial agents and chemotherapy Abstract HIV V106I;V179D;V106I;V179D 89;15;78;142 94;20;83;147 20124001 Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. Structural analysis indicated that ETV can overcome the repulsive interactions caused by the combination of V106I and V179D through fine-tuning of its binding module to RT facilitated by its plastic structure, whereas EFV and NVP cannot because of their rigid structures. 2010 Antimicrobial agents and chemotherapy Abstract HIV V106I;V179D 108;118 113;123 RT 169 171 20124001 Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. The combination of V106I and V179D is a newly identified NNRTI resistance pattern of mutations. 2010 Antimicrobial agents and chemotherapy Abstract HIV V106I;V179D 19;29 24;34 NNRTI 57 62 20124001 Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. To select highly NNRTI-resistant HIV-1 in vitro, monoclonal HIV-1 strains harboring V106I and V179D (HIV-1(V106I) and HIV-1(V179D)) were propagated in the presence of increasing concentrations of efavirenz (EFV). 2010 Antimicrobial agents and chemotherapy Abstract HIV V106I;V179D;V106I;V179D 84;94;107;124 89;99;112;129 NNRTI 17 22 20124005 International cohort analysis of the antiviral activities of zidovudine and tenofovir in the presence of the K65R mutation in reverse transcriptase. A K65R mutation in HIV-1 reverse transcriptase can occur with the failure of tenofovir-, didanosine-, abacavir-, and, in some cases, stavudine-containing regimens and leads to reduced phenotypic susceptibility to these drugs and hypersusceptibility to zidovudine, but its clinical impact is poorly described. 2010 Antimicrobial agents and chemotherapy Abstract HIV K65R 2 6 RT 25 46 20124005 International cohort analysis of the antiviral activities of zidovudine and tenofovir in the presence of the K65R mutation in reverse transcriptase. Given its tolerability, tenofovir may be the preferred agent over zidovudine even in the presence of the K65R mutation. 2010 Antimicrobial agents and chemotherapy Abstract HIV K65R 105 109 20124005 International cohort analysis of the antiviral activities of zidovudine and tenofovir in the presence of the K65R mutation in reverse transcriptase. In the presence of K65R, zidovudine and tenofovir are associated with similar reductions in HIV RNA levels. 2010 Antimicrobial agents and chemotherapy Abstract HIV K65R 19 23 20124005 International cohort analysis of the antiviral activities of zidovudine and tenofovir in the presence of the K65R mutation in reverse transcriptase. We identified isolates with the K65R mutation within the Stanford Resistance Database and a French cohort for which subsequent treatment and virological response data were available. 2010 Antimicrobial agents and chemotherapy Abstract HIV K65R 32 36 20124969 Emerging mutations at virological failure of HAART combinations containing tenofovir and lamivudine or emtricitabine. At multivariate analysis, the emergence of K70R (P = 0.002), M184V (P = 0.031), T215F (P = 0.020) and Y181C (P = 0.005) was significantly more common in 3TC-treated than in FTC-treated patients, with an odds ratio of 4, 1.56, 1.89 and 3.84, respectively. 2010 AIDS (London, England) Abstract HIV K70R;M184V;T215F;Y181C 43;61;80;102 47;66;85;107 20130473 Connection domain mutations in treatment-experienced patients in the OPTIMA trial. Frequencies of E312Q, Y318F, G333D, G333E, G335C, G335D, N348I, A360I, A360V, V365I, A371V, A376S, and E399G were compared with a treatment-naive population. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A360I;A360V;A371V;A376S;E312Q;E399G;G333D;G333E;G335C;G335D;N348I;V365I;Y318F 64;71;85;92;15;103;29;36;43;50;57;78;22 69;76;90;97;20;108;34;41;48;55;62;83;27 20130473 Connection domain mutations in treatment-experienced patients in the OPTIMA trial. On univariate analysis, A371V was associated with lack of virologic response, as was having any CD mutation on multivariate analysis. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A371V 24 29 2013336 Purification of HIV-1 wild-type protease and characterization of proteolytically inactive HIV-1 protease mutants by pepstatin A affinity chromatography. A third mutant protease Arg-87----Glu) was apparently unable to bind to pepstatin A under similar conditions. 1991 FEBS letters Abstract HIV R87E 24 37 PR 15 23 2013336 Purification of HIV-1 wild-type protease and characterization of proteolytically inactive HIV-1 protease mutants by pepstatin A affinity chromatography. Two proteolytically inactive HIV-1 mutant proteases (Arg-87----Lys; Asn-88----Glu) were found to bind to pepstatin A agarose, and and they were purified as the wild-type protease. 1991 FEBS letters Abstract HIV N88E;R87K 68;53 81;66 PR;PR 42;170 51;178 20137514 [Genetic characteristics of HIV-1 primary drug resistance-associated mutations in treatment-naive individuals in Liaoning province, 2004-2008]. A major mutation position I54S in PR implied that it would be the time to commence a higher level drug regimen. 2009 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I54S 26 30 PR 34 36 20137514 [Genetic characteristics of HIV-1 primary drug resistance-associated mutations in treatment-naive individuals in Liaoning province, 2004-2008]. A71V or L10V only, respectively, substitution in PR was found in 3 samples, but no any worse with drug sensitivity. 2009 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV L10V;A71V 8;0 12;4 PR 49 51 20137514 [Genetic characteristics of HIV-1 primary drug resistance-associated mutations in treatment-naive individuals in Liaoning province, 2004-2008]. The most frequent substitutions (4/13) in the RT region at positions P225H, K238S, V179D, K238T and a major position I54S in PR implied to a multiple drug-resistance. 2009 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I54S;K238S;K238T;P225H;V179D 117;76;90;69;83 121;81;95;74;88 PR;RT 125;46 127;48 20137515 [Study on the transmission of drug resistant human immunodeficiency virus-1 in Henan province]. In one specimen, a mutation (K103N) in reverse transcriptase was identified which caused high level resistance to NNRTIs, but no proteinase inhibitor mutation was found in protein region. 2009 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV K103N 29 34 RT;NNRTI 39;114 60;120 20137928 N1-Heterocyclic pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Inhibitor 1 is active against NNRTI-resistant viruses including RT mutant K103N. 2010 Bioorganic & medicinal chemistry letters Abstract HIV K103N 74 79 NNRTI;RT 30;64 35;66 20146734 High level of primary drug resistance in Mali. Several polymorphisms in the C-terminal domain of reverse transcriptase were observed: A371V (in 63.4% of patients), G335D (76.2%), E399D (10.9%) and G333E (1%). 2010 HIV medicine Abstract HIV A371V;E399D;G333E;G335D 87;132;150;117 92;137;155;122 RT 50 71 20146734 High level of primary drug resistance in Mali. Taking into consideration other polymorphisms in protease such as L10I/V and 33F, primary resistance could reach 28.7% (95% CI 19.9-37.5%). 2010 HIV medicine Abstract HIV L10I;L10V 66;66 72;72 PR 49 57 20146734 High level of primary drug resistance in Mali. The most frequent mutations were T215A/Y for NRTIs and K103N/T for NNRTIs. 2010 HIV medicine Abstract HIV K103N;K103T;T215A;T215Y 55;55;33;33 62;62;40;40 NNRTI;NRTI 67;45 73;50 20156103 Comparison of genotypic resistance mutations in treatment-naive HIV type 1-infected patients in Korea and China. Although no major TDR was observed within the study population, some resistance-associated mutations in the reverse transcriptase region were observed (V118I 9.2%, V179D 7.9%). 2010 AIDS research and human retroviruses Abstract HIV V118I;V179D 152;164 158;169 RT 108 129 20156103 Comparison of genotypic resistance mutations in treatment-naive HIV type 1-infected patients in Korea and China. The frequencies of resistance-associated mutations in NNRTI (V179D) and PI minor mutations were higher in Korean patients compared with Chinese patients (13.6% vs. 2010 AIDS research and human retroviruses Abstract HIV V179D 61 66 NNRTI;PI 54;72 59;74 20156106 Characterization of HIV type 1 genotypes and drug resistance mutations among drug-naive HIV type 1-infected patients in Northern Vietnam. Major protease inhibitor resistance mutations, such as L33F, M46I, and M46L, were found in three patients (1.7%). 2010 AIDS research and human retroviruses Abstract HIV L33F;M46I;M46L 55;61;71 59;65;75 PR 6 14 20156106 Characterization of HIV type 1 genotypes and drug resistance mutations among drug-naive HIV type 1-infected patients in Northern Vietnam. Major reverse-transcriptase inhibitor (RTI) resistance mutations were found in seven patients (4.5%), four of whom had single mutations: A62V (nucleoside RTI resistance mutation) in two cases and K103N and Y181C (nonnucleoside RTI resistance mutation) in one case each. 2010 AIDS research and human retroviruses Abstract HIV A62V;K103N;Y181C 137;196;206 141;201;211 RT;RT;RT;RT 6;39;154;227 27;42;157;230 20156454 Visualizing the molecular interactions of a nucleotide analog, GS-9148, with HIV-1 reverse transcriptase-DNA complex. Interestingly, the 2'-fluoro moiety of GS-9148-diphosphate was found in close proximity to the Q151 side chain, potentially explaining the observed moderately reduced susceptibly to GS-9148 conferred by Q151M mutation. 2010 Journal of molecular biology Abstract HIV Q151M 203 208 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. Consensus sequencing and the more sensitive oligonucleotide ligation assay were performed on samples obtained on postpartum days 7-10, 37-45, and 120 (if the HIV load was >500 copies/mL) to detect K103N/Y181C/G190A mutations. 2010 Clinical infectious diseases Abstract HIV G190A;K103N;Y181C 209;197;203 214;202;208 20160632 Impact of human leukocyte antigen-B*51-restricted cytotoxic T-lymphocyte pressure on mutation patterns of nonnucleoside reverse transcriptase inhibitor resistance. Computational analysis indicated that I135T and E138K cooperatively extend the gap between the binding site of reverse transcriptase and NNRTI. 2010 AIDS (London, England) Abstract HIV E138K;I135T 48;38 53;43 RT;NNRTI 111;137 132;142 20160632 Impact of human leukocyte antigen-B*51-restricted cytotoxic T-lymphocyte pressure on mutation patterns of nonnucleoside reverse transcriptase inhibitor resistance. DESIGN: The prevalence of HIV-1 harboring an escape mutation, I135X, in a major epitope of HLA-B*51-restricted CTL located in reverse transcriptase is increasing worldwide. 2010 AIDS (London, England) Abstract HIV I135X 62 67 RT 126 147 20160632 Impact of human leukocyte antigen-B*51-restricted cytotoxic T-lymphocyte pressure on mutation patterns of nonnucleoside reverse transcriptase inhibitor resistance. METHODS: Monoclonal HIV-1 sequences harboring each of the escape mutations, including I135L (HIV-1I135L), I135V (HIV-1I135V), I135T (HIV-1I135T), and I135R (HIV-1I135R) in reverse transcriptase, and a wild-type monoclonal HIV-1 (HIV-1WT) were cultured in the presence of increasing concentrations of efavirenz. 2010 AIDS (London, England) Abstract HIV I135L;I135R;I135T;I135V 86;150;126;106 91;155;131;111 RT 172 193 20160632 Impact of human leukocyte antigen-B*51-restricted cytotoxic T-lymphocyte pressure on mutation patterns of nonnucleoside reverse transcriptase inhibitor resistance. RESULTS: E138K emerged during the cultural passages of HIV-1I135V, HIV-1I135T, and HIV-1I135R, but not during the passages of HIV-1WT. 2010 AIDS (London, England) Abstract HIV I135T;I135V;E138K 72;60;9 77;65;14 20160632 Impact of human leukocyte antigen-B*51-restricted cytotoxic T-lymphocyte pressure on mutation patterns of nonnucleoside reverse transcriptase inhibitor resistance. The combination of I135T, the most frequent escape mutation, and E138K (HIV-1I135T/E138K) conferred significant resistance to efavirenz, nevirapine, and etravirine. 2010 AIDS (London, England) Abstract HIV E138K;E138K;I135T 65;83;19 70;88;24 20160632 Impact of human leukocyte antigen-B*51-restricted cytotoxic T-lymphocyte pressure on mutation patterns of nonnucleoside reverse transcriptase inhibitor resistance. The HIV-1I135L/E138K and HIV-1I135R/E138K were significantly resistant to nevirapine and etravirine, respectively, though each solo of escape mutations and E138K did not confer significant resistance to NNRTI. 2010 AIDS (London, England) Abstract HIV I135L;I135R;E138K;E138K;E138K 9;30;15;36;156 14;35;20;41;161 NNRTI 203 208 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. CONCLUSION: The acquisition of N348I in HIV-1 reverse transcriptase - which can occur early in therapy, oftentimes before TAMs - may provide a simple genetic pathway that allows the virus to select both TAMs and mutations that are antagonistic toward TAMs. 2010 AIDS (London, England) Abstract HIV N348I 31 36 RT 46 67 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. DESIGN AND METHODS: The ZDV monophosphate and ribonuclease H activities of recombinant-purified HIV-1 reverse transcriptase-containing combinations of K70R, N348I and Y181C, L74V or M184V were assessed using standard biochemical and antiviral assays. 2010 AIDS (London, England) Abstract HIV K70R;L74V;M184V;N348I;Y181C 151;174;182;157;167 155;178;187;162;172 RT 102 123 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. However, the N348I mutation compensated for this antagonism on RNA/DNA template/primers by significantly decreasing the frequency of secondary ribonuclease H cleavages that reduce the overall efficiency of the excision reaction. 2010 AIDS (London, England) Abstract HIV N348I 13 18 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. In this study, we examined whether N348I compensates for the antagonism of the TAM K70R by Y181C, L74V and M184V. 2010 AIDS (London, England) Abstract HIV K70R;L74V;M184V;N348I;Y181C 83;98;107;35;91 87;102;112;40;96 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. L74V and M184V) resistance mutations in HIV-1 reverse transcriptase are antagonistic toward thymidine analogue mutations (TAMs) that confer zidovudine (ZDV) resistance. 2010 AIDS (London, England) Abstract HIV M184V;L74V 9;0 14;4 RT 46 67 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. RESULTS: As expected, the introduction of the Y181C, L74V or M184V mutations into K70R HIV-1 reverse transcriptase significantly diminished the ATP-mediated ZDV monophosphate excision activity of the enzyme. 2010 AIDS (London, England) Abstract HIV K70R;L74V;M184V;Y181C 82;53;61;46 86;57;66;51 RT 93 114 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. The N348I mutation in the connection domain of reverse transcriptase also confers ZDV resistance; however, the mechanisms involved are different from TAMs. 2010 AIDS (London, England) Abstract HIV N348I 4 9 RT 47 68 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Y181C) and nucleoside (e.g. 2010 AIDS (London, England) Abstract HIV Y181C 0 5 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. Allele-specific real-time PCR (AS-PCR) systems, developed for Q148H, Q148R and N155H mutations, were performed at baseline for antiretroviral-experienced patients. 2010 AIDS (London, England) Abstract HIV N155H;Q148H;Q148R 79;62;69 84;67;74 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. CONCLUSION: Q148R variants were frequently detected, always at low-level, in antiretroviral-experienced and naive patients. 2010 AIDS (London, England) Abstract HIV Q148R 12 17 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. However, we did not find any association between the presence of Q148R minority variants and an increased risk of virological failure. 2010 AIDS (London, England) Abstract HIV Q148R 65 70 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. In antiretroviral-experienced patients, Q148R minority variants were frequently detected (26/32 patients, 81%) at low-level frequency (median = 0.40%), whereas no minority variants exhibiting Q148H or N155H mutation were found. 2010 AIDS (London, England) Abstract HIV N155H;Q148H;Q148R 201;192;40 206;197;45 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. Q148R minority variants were also found in 86% of antiretroviral-naive patients, a prevalence significantly higher than that of K103N minority variants (26%). 2010 AIDS (London, England) Abstract HIV K103N;Q148R 128;0 133;5 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. RESULTS: The limits of detection of AS-PCR systems were 0.10, 0.10 and 0.05% for Q148H, Q148R and N155H mutations, respectively. 2010 AIDS (London, England) Abstract HIV N155H;Q148H;Q148R 98;81;88 103;86;93 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. Samples from antiretroviral-naive patients were tested with the Q148R AS-PCR assay. 2010 AIDS (London, England) Abstract HIV Q148R 64 69 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. Twenty-four of 26 patients exhibiting Q148R variants were virological responders but four of them displayed a delayed virological response occurring between W18 and W36. 2010 AIDS (London, England) Abstract HIV Q148R 38 43 20160635 High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. Two patients exhibited virological failure under raltegravir, both harboring Q148R minority variants at baseline. 2010 AIDS (London, England) Abstract HIV Q148R 77 82 20163340 Suboptimal etravirine activity is common during failure of nevirapine-based combination antiretroviral therapy in a cohort infected with non-B subtype HIV-1. The most common etravirine resistance associated mutations were Y181C (42.9%), G190A (25.3%), H221Y (19.8%), A98G (18.7%), K101E (16.5%), and V90I (12.1%). 2010 Current HIV research Abstract HIV A98G;G190A;H221Y;K101E;V90I;Y181C 109;79;94;123;142;64 113;84;99;128;146;69 20163482 HIV-1 proviral resistance mutations: usefulness in clinical practice. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H). 2010 HIV medicine Abstract HIV M184I;M184I;M184M;Y188H;Y188Y 68;75;75;87;87 73;82;82;94;94 20163482 HIV-1 proviral resistance mutations: usefulness in clinical practice. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. 2010 HIV medicine Abstract HIV K103K;K103N;M184I;M184M;M184M;M184V;M46I;M46M 70;70;61;52;61;52;82;82 77;77;68;59;68;59;88;88 20164190 The acyclic 2,4-diaminopyrimidine nucleoside phosphonate acts as a purine mimetic in HIV-1 reverse transcriptase DNA polymerization. PMEO-DAPym-pp is incorporated more efficiently than (R)PMPA-pp by mutant K65R HIV-1 RT and is not as efficiently excised as (R)PMPA by HIV-1 RT containing thymidine analog mutations. 2010 The Journal of biological chemistry Abstract HIV K65R 73 77 RT;RT 84;141 86;143 20166821 Protease inhibitor-based antiretroviral prophylaxis during pregnancy and the development of drug resistance. Primary resistance mutations were found in 2 patients (nonnucleoside reverse-transcriptase inhibitor resistance, K103N; protease inhibitor resistance, G48V). 2010 Clinical infectious diseases Abstract HIV G48V;K103N 151;113 155;118 NNRTI;PR 55;120 90;128 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. BACKGROUND: The connection domain mutation N348I confers resistance to zidovudine (AZT) and is associated with the lamivudine (3TC) mutation M184V. 2010 The Journal of infectious diseases Abstract HIV M184V;N348I 141;43 146;48 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. Biochemical data show that N348I can partially compensate for the diminution in processive DNA synthesis and the reduction in AZT excision associated with M184V. 2010 The Journal of infectious diseases Abstract HIV M184V;N348I 155;27 160;32 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. Compensatory interactions between N348I and M184V help to explain these findings. 2010 The Journal of infectious diseases Abstract HIV M184V;N348I 44;34 49;39 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. CONCLUSION: In vivo selection of N348I is driven by AZT and is further facilitated when 3TC is coadministered. 2010 The Journal of infectious diseases Abstract HIV N348I 33 38 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. Furthermore, virological analyses demonstrate that N348I confers low-level resistance to AZT and partly restores the reduced RT activity of the M184V variant. 2010 The Journal of infectious diseases Abstract HIV M184V;N348I 144;51 149;56 RT 125 127 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. Mutant reverse transcriptases (RTs) containing M184V and/or N348I were generated to study enzymatic and virological properties. 2010 The Journal of infectious diseases Abstract HIV M184V;N348I 47;60 52;65 RT;RT 7;31 29;34 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. N348I was observed in 3 (6%), 0, and 4 (40%) of these patients, respectively. 2010 The Journal of infectious diseases Abstract HIV N348I 0 5 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. Rates of N348I emergence were compared between treatment groups. 2010 The Journal of infectious diseases Abstract HIV N348I 9 14 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. The rate of N348I emergence was increased by 5-fold in the AZT/3TC group (11.7 instances [95% confidence interval {CI}, 3.2-30.1 instances] per 100 person-years of receipt of AZT), compared with the rate noted for the AZT group (2.3 instances [95% CI, 0.4-6.8 instances] per 100 person-years of receipt of AZT; P = .04). 2010 The Journal of infectious diseases Abstract HIV N348I 12 17 20170373 Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. We explored the biochemical and virological influence of N348I in the context of M184V. 2010 The Journal of infectious diseases Abstract HIV M184V;N348I 81;57 86;62 20174661 HIV drug resistance surveillance using pooled pyrosequencing. Using Sanger sequencing, two TDR mutations, M46L and I84V, were each detected as mixtures at a frequency of 1.04% (1/96). 2010 PloS one Abstract HIV I84V;M46L 53;44 57;48 20180140 Antiretroviral drug resistance mutations in the reverse transcriptase gene of HIV-1 isolates from Northern Indian patients: a follow-up study. Phylogenetic analysis revealed two new recombinant forms, CRF_CH and CRF_CK, and an accessory non-nucleoside reverse transcriptase inhibitor mutation E138A, not previously reported from India. 2010 Archives of virology Abstract HIV E138A 150 155 NNRTI 94 130 20181911 Detection of HIV-1 drug resistance in women following administration of a single dose of nevirapine: comparison of plasma RNA to cellular DNA by consensus sequencing and by oligonucleotide ligation assay. Nevirapine-resistant HIV-1 genotypes (with the mutations K103N, Y181C, and/or G190A) from 21 women were evaluated 10 days and 6 weeks after sdNVP administration and at the initiation of ART. 2010 Journal of clinical microbiology Abstract HIV G190A;K103N;Y181C 78;57;64 83;62;69 20185094 Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. 2010 The Lancet. Infectious diseases Abstract HIV K103N;M184V 151;107 156;112 NNRTI 182 218 20185094 Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Thymidine-analogue mutations and the K65R mutation were less common. 2010 The Lancet. Infectious diseases Abstract HIV K65R 37 41 20188624 Using of nevirapine is associated with intermediate and reduced response to etravirine among HIV-infected patients who experienced virologic failure in a resource-limited setting. Common ETV-RAMs included Y181C (27%), G190A (17%), and K101E (10%). 2010 Journal of clinical virology Abstract HIV G190A;K101E;Y181C 38;55;25 43;60;30 20188624 Using of nevirapine is associated with intermediate and reduced response to etravirine among HIV-infected patients who experienced virologic failure in a resource-limited setting. Higher proportion of K101E, K101P, Y181C, G190S, and M230L were found in patients with a score of > or =2.5 (p<0.05, all). 2010 Journal of clinical virology Abstract HIV G190S;K101E;K101P;M230L;Y181C 42;21;28;53;35 47;26;33;58;40 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Clinical studies have demonstrated an increased frequency of K65R in association with suboptimal d4T and ddI regimens, as well as nevirapine and its resistance mutations Y181C and G190A. 2009 HIV therapy Abstract HIV G190A;K65R;Y181C 180;61;170 185;65;175 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In general, the K65R mutation is rarely selected (1.7-4%) with tenofovir disoproxil fumarate (TDF), abacavir (ABC), didanosine (ddI), and stavudine (d4T), as compared with the high incidence (>40%) of thymidine analog mutations associated with zidovudine and d4T. 2009 HIV therapy Abstract HIV K65R 16 20 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Nevertheless, surprisingly high levels of treatment failures and K65R resistance may be associated with triple nucleoside analog regimens. 2009 HIV therapy Abstract HIV K65R 65 69 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Optimizing regimens may attenuate the emergence of K65R, leading to better long-term treatment management in different geographic settings. 2009 HIV therapy Abstract HIV K65R 51 55 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The high barrier to the development of K65R may reflect a combination of factors, including the high potency of K65R-selecting drugs, including recommended TDF/emtricitabine and ABC/lamivudine (ABC/3TC) combinations; the partial (low-intermediate level) profile of cross-resistance conferred by K65R to TDF, ABC and 3TC; the favorable viral fitness constraint imposed by K65R and the 3TC/emtricitabine-associated M184V mutations; the bidirectional antagonism between the K65R and thymidine analog mutation pathways; and unique RNA structural considerations in the region surrounding codon 65. 2009 HIV therapy Abstract HIV K65R;K65R;K65R;K65R;K65R;M184V 39;112;295;371;471;413 43;116;299;375;475;418 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The potential for the development of the K65R mutation in subtype C is particularly problematic wherein a signature KKK nucleotide motif, at codons 64, 65 and 66 in reverse transcriptase, appear to lead to template pausing, facilitating the selection of K65R. 2009 HIV therapy Abstract HIV K65R;K65R 41;254 45;258 RT 165 186 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. This selection of K65R may be reduced by the inclusion of zidovudine in two-four nucleoside reverse-transcriptase regimens. 2009 HIV therapy Abstract HIV K65R 18 22 NRTI 81 113 20194692 Combinations of mutations in the connection domain of human immunodeficiency virus type 1 reverse transcriptase: assessing the impact on nucleoside and nonnucleoside reverse transcriptase inhibitor resistance. Furthermore, the effect of N348I on NRTI and NNRTI resistance was confirmed. 2010 Antimicrobial agents and chemotherapy Abstract HIV N348I 27 32 NNRTI;NRTI 45;36 50;40 20194692 Combinations of mutations in the connection domain of human immunodeficiency virus type 1 reverse transcriptase: assessing the impact on nucleoside and nonnucleoside reverse transcriptase inhibitor resistance. HIV-1 with either N348I or T369I/V demonstrated reduced susceptibility to nevirapine (NVP), efavirenz (EFV), delaviridine (DLV), and zidovudine (ZDV) compared to wild-type HIV-1. 2010 Antimicrobial agents and chemotherapy Abstract HIV N348I;T369I;T369V 18;27;27 23;34;34 20194692 Combinations of mutations in the connection domain of human immunodeficiency virus type 1 reverse transcriptase: assessing the impact on nucleoside and nonnucleoside reverse transcriptase inhibitor resistance. However, HIV-1 with T369I and N348I demonstrated 10- to 60-fold resistance to these same drugs. 2010 Antimicrobial agents and chemotherapy Abstract HIV N348I;T369I 30;20 35;25 20194692 Combinations of mutations in the connection domain of human immunodeficiency virus type 1 reverse transcriptase: assessing the impact on nucleoside and nonnucleoside reverse transcriptase inhibitor resistance. In the present study, novel mutations in the connection domain of RT (T369I/V), first identified in patient-derived viruses, were characterized, and their effects on NNRTI and NNRTI susceptibility were determined. 2010 Antimicrobial agents and chemotherapy Abstract HIV T369I;T369V 70;70 77;77 NNRTI;NNRTI;RT 166;176;66 171;181;68 20194692 Combinations of mutations in the connection domain of human immunodeficiency virus type 1 reverse transcriptase: assessing the impact on nucleoside and nonnucleoside reverse transcriptase inhibitor resistance. Introduction of T369I, N348I, or T369I/N348I also reduced replication capacity (RC). 2010 Antimicrobial agents and chemotherapy Abstract HIV N348I;N348I;T369I;T369I 39;23;16;33 44;28;21;38 20195662 Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease. As a consequence, the protein-ligand contacts lost upon the V82A mutation are restored by 80s loop motions for the APV-bound, but not for the RTV-bound form. 2010 Journal of molecular modeling Abstract HIV V82A 60 64 20195662 Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease. For the unliganded double mutant protease molecular dynamics simulations revealed a contraction of the ligand binding pocket, which is enhanced by the I54V mutation. 2010 Journal of molecular modeling Abstract HIV I54V 151 155 PR 33 41 20195662 Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease. In the present work we investigated the structural properties of a triple mutant (I54V-V82A-L90M) and a double mutant (V82A-L90M) that both confer strong resistance to ritonavir (RTV), but not to amprenavir (APV). 2010 Journal of molecular modeling Abstract HIV I54V;L90M;L90M;V82A;V82A 82;92;124;87;119 86;96;128;91;123 20196655 Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy. CONCLUSIONS: Minority variants, in particular viruses harboring the M184V mutation, were efficiently suppressed in patients with acute infection who received a ritonavir-boosted PI and 2 NRTIs (most regimens included lamivudine). 2010 The Journal of infectious diseases Abstract HIV M184V 68 73 NRTI;PI 187;178 192;180 20196655 Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy. METHODS: Plasma samples obtained prior to initiation of ART from 109 patients with primary HIV infection and samples obtained during viral decay during early ART from 17 of these 109 patients were tested by allele-specific polymerase chain reaction for K103N and M184V variants. 2010 The Journal of infectious diseases Abstract HIV K103N;M184V 253;263 258;268 Pol 223 233 HIV infections 83 104 20196655 Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy. RESULTS: K103N and/or M184V mutations were detected in 15 (13.8%) of 109 patients prior to ART as minority variants. 2010 The Journal of infectious diseases Abstract HIV K103N;M184V 9;22 14;27 20196655 Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy. Under this high genetic resistance barrier regimen, the M184V was not further selected. 2010 The Journal of infectious diseases Abstract HIV M184V 56 61 20219553 In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor. Characterization of the observed mutations by site-directed mutagenesis in the isogenic HXB2D background demonstrated that a minimum of two or more mutations were required for significant loss of susceptibility, with the exception of Y188L, which requires a two-nucleotide change. 2010 Antiviral research Abstract HIV Y188L 234 239 20219553 In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor. Patterns containing F227C or quadruple mutations selected by RO-0335 showed a low relative fitness value when compared to wild-type HXB2D. 2010 Antiviral research Abstract HIV F227C 20 25 20219553 In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor. Two pathways to loss of susceptibility to RO-0335 were observed, containing patterns of amino acid changes at either V106I/A plus F227C (with additional contributions from A98G, V108I, E138K, M230L and P236L) or V106I/Y188L (with a potential contribution from L100I, E138K and Y181C). 2010 Antiviral research Abstract HIV A98G;E138K;E138K;F227C;L100I;M230L;P236L;V106A;V106I;V106I;V108I;Y181C;Y188L 172;185;267;130;260;192;202;117;117;212;178;277;218 176;190;272;135;265;197;207;124;124;217;183;282;223 20219933 A novel molecular mechanism of dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. Combining the D549N mutant with NNRTI BP mutants further increases NNRTI resistance from 3- to 30-fold, supporting the role of NNRTI-RT affinity in our NNRTI resistance model. 2010 Journal of virology Abstract HIV D549N 14 19 NNRTI;NNRTI;NNRTI;NNRTI;RT 32;67;127;152;133 37;72;132;157;135 20219933 A novel molecular mechanism of dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. D549N, Q475A, and Y501A mutants, which reduce RNase H cleavage, enhance resistance to nevirapine (NVP) and delavirdine (DLV), but not to efavirenz (EFV) and etravirine (ETR), consistent with their increase in affinity for RT. 2010 Journal of virology Abstract HIV Q475A;Y501A;D549N 7;18;0 12;23;5 RT 222 224 20227665 Flexible use of nuclear import pathways by HIV-1. HIV-1 harboring the N74D mutation in CA fails to interact with CPSF6 and evades the nuclear import restriction. 2010 Cell host & microbe Abstract HIV N74D 20 24 Capsid 37 39 20227665 Flexible use of nuclear import pathways by HIV-1. Interestingly, whereas wild-type HIV-1 requires NUP153, N74D HIV-1 mimics feline immunodeficiency virus nuclear import requirements and is more sensitive to NUP155 depletion. 2010 Cell host & microbe Abstract HIV N74D 56 60 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. (2) Charged mutations (I37K, Q40K, and V38E) lead to significant Coulombic changes that weaken favorable van der Waals interactions. 2010 Biochemistry Abstract HIV I37K;Q40K;V38E 23;29;39 27;33;43 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. (3) Q40K is more detrimental than I37K because of interaction differences with a polar/charged patch on T20 in the initial (wild-type) state. 2010 Biochemistry Abstract HIV I37K 34 38 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. (4) Resistance for L33S versus L33Q likely involves side chain packing differences in the final (mutated) state. 2010 Biochemistry Abstract HIV L33Q;L33S 31;19 35;23 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In addition, seven deleterious gp41 point mutations (L33Q, L33S, G36V, I37K, V38E, Q40H, and Q40K) were simulated, and all correctly exhibited decreases in the level of binding, including the fact that L33Q and Q40K are most detrimental. 2010 Biochemistry Abstract HIV G36V;I37K;L33Q;L33Q;L33S;Q40H;Q40K;Q40K;V38E 65;71;53;202;59;83;93;211;77 69;75;57;206;63;87;97;215;81 gp41 31 35 20230797 Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function. The introduction of W596L and W610F mutations to the DSR of HIV-1(QH1549.13) blocked viral entry and hemifusion without affecting gp120-gp41 association. 2010 Biochemical and biophysical research communications Abstract HIV W596L;W610F 20;30 25;35 gp120;gp41 130;136 135;140 20231447 Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution. In this study we characterize a single leucine to serine substitution at position 669 (L669S) in the gp41 Env MPER that confers >250-fold more neutralization sensitivity to 2F5 and 4E10 mAbs than does the wild-type gp41 sequence. 2010 Proc Natl Acad Sci U S A Abstract HIV L669S;L669S 87;39 92;85 gp41;gp41;Env 101;215;106 105;219;109 20231447 Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution. On synthetic liposomes, increased solvent exposure of MPER tryptophan residues and stable docking of 2F5 and 4E10 mAbs to mutant MPER peptide liposomes indicate more favorable membrane orientation of MPER neutralizing epitopes with L669S substitution. 2010 Proc Natl Acad Sci U S A Abstract HIV L669S 232 237 20231447 Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution. These data suggest that a major contribution to the L669S mutant virus phenotype of enhanced susceptibility to MPER mAbs is prolonged exposure of the MPER neutralizing epitope during viral entry. 2010 Proc Natl Acad Sci U S A Abstract HIV L669S 52 57 20236364 Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA). Frequent RAMs were Y181C, G190A, K101E and A98G, whereas V179F, Y181V and G190S appeared in <5% of sequences. 2010 HIV medicine Abstract HIV A98G;G190A;G190S;K101E;V179F;Y181C;Y181V 43;26;74;33;57;19;64 47;31;79;38;62;24;69 20236364 Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA). The DUET studies showed that at least three TMC125-associated mutations were required to impair the efficacy of the drug and Y181C/V, V179F and G190S had the greatest effect on response. 2010 HIV medicine Abstract HIV G190S;V179F;Y181C;Y181V 144;134;125;125 149;139;132;132 20307579 Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. Here we report a detailed enzymatic analysis elucidating the molecular mechanism of interaction between benzimidazol-2-one derivatives and the K103N mutant RT. 2010 Antiviral research Abstract HIV K103N 143 148 RT 156 158 20307579 Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. However, they were still of limited efficacy towards the K103N mutant. 2010 Antiviral research Abstract HIV K103N 57 62 20307579 Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. The loss of potency of these molecules towards the K103N RT was specifically due to a reduction of their association rate to the enzyme. 2010 Antiviral research Abstract HIV K103N 51 56 RT 57 59 20307579 Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutation. Unexpectedly, these compounds showed a strongly reduced dissociation rate from the K103N mutant, as compared to the wild type enzyme, suggesting that, once occupied by the drug, the mutated binding site could achieve a more stable interaction with these molecules. 2010 Antiviral research Abstract HIV K103N 83 88 20307984 Synthesis and biological evaluation of 4-(hydroxyimino)arylmethyl diarylpyrimidine analogues as potential non-nucleoside reverse transcriptase inhibitors against HIV. 4-(4-((Hydroxyimino) (3-methoxyphenyl)methyl)pyrimidin-2-ylamino)benzonitrile (12n) was identified as the most active compound of this new series (EC(50)=0.025microM, SI >1223) associated with moderate activity against HIV-1 double mutant strains (K103N+Y181C) (EC(50)=8.72microM) in addition to its anti-HIV-2 activity with an EC(50) value of 8.31microM. 2010 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 248;254 253;259 20308382 Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. 2010 Antimicrobial agents and chemotherapy Abstract HIV V370A;V7A 75;103 80;106 SP1;SP1 81;99 84;102 20308382 Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein-V230I), is also a major mutation conferring resistance to BVM. 2010 Antimicrobial agents and chemotherapy Abstract HIV V230I;V362I 94;76 99;81 Capsid;Capsid 55;83 61;85 20308382 Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. 2010 Antimicrobial agents and chemotherapy Abstract HIV A364V;A366T;A366V;H358Y;L363F;L363M 123;140;130;102;116;109 128;145;135;107;121;114 Gag 79 82 20308384 The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. Phenotyping assays with TZM-bl cells confirmed that M230L conferred various degrees of resistance to each of the NNRTIs tested. 2010 Antimicrobial agents and chemotherapy Abstract HIV M230L 52 57 NNRTI 113 119 20308384 The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. Recombinant HIV-1 WT and M230L mutant RT enzymes were purified; and both biochemical and cell-based phenotypic assays confirmed that M230L conferred resistance to each of EFV, NVP, and ETR. 2010 Antimicrobial agents and chemotherapy Abstract HIV M230L;M230L 25;133 30;138 RT 38 40 20308384 The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. Recombinant viruses containing M230L displayed an 8-fold decrease in RC compared to that of the parental wild-type (WT) virus. 2010 Antimicrobial agents and chemotherapy Abstract HIV M230L 31 36 20308384 The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. RT that contained M230L was also deficient in regard to each of minus-strand DNA synthesis, both DNA- and RNA-dependent polymerase activities, processivity, and RNase H activity, suggesting that this mutation contributes to diminished viral replication kinetics. 2010 Antimicrobial agents and chemotherapy Abstract HIV M230L 18 23 Pol;RT 120;0 130;2 20308384 The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. The M230L mutation in HIV-1 reverse transcriptase (RT) is associated with resistance to first-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs). 2010 Antimicrobial agents and chemotherapy Abstract HIV M230L 4 9 NNRTI;RT;NNRTI;RT 105;28;153;51 140;49;159;53 20308384 The M230L nonnucleoside reverse transcriptase inhibitor resistance mutation in HIV-1 reverse transcriptase impairs enzymatic function and viral replicative capacity. The present study was designed to determine the effects of M230L on enzyme function, viral replication capacity (RC), and the extent to which M230L might confer resistance to the second-generation NNRTI etravirine (ETR) as well as to the first-generation NNRTIs efavirenz (EFV) and nevirapine (NVP). 2010 Antimicrobial agents and chemotherapy Abstract HIV M230L;M230L 59;142 64;147 NNRTI;NNRTI 197;255 202;261 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Charge substitutions of surface residues (E21, D30, E34, E35, and F99) to neutral or positively charged amino acids failed to restore protease autoprocessing in the context of H69E mutation. 2010 Retrovirology Abstract HIV H69E 176 180 PR 134 142 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Mutagenesis analyses identified C95 as the primary determinant that dampened the inhibitory effect of H69E. 2010 Retrovirology Abstract HIV H69E 102 106 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. RESULTS: Interestingly, H69E mutation in the context of a laboratory adapted NL4-3 protease showed only moderate inhibition (approximately 4-fold) on protease maturation. 2010 Retrovirology Abstract HIV H69E 24 28 PR;PR 83;150 91;158 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. There are six point mutations (Q7K, L33I, N37S, L63I, C67A, and C95A) between the NL4-3 and the pseudo wild type proteases suggesting that the H69E effect is influenced by other residues. 2010 Retrovirology Abstract HIV C67A;C95A;H69E;L33I;L63I;N37S;Q7K 54;64;143;36;48;42;31 58;68;147;40;52;46;34 PR 113 122 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. We previously reported that H69E mutation in a pseudo wild type protease sequence significantly (>20-fold) impedes protease maturation in an in vitro autoprocessing assay and in transfected mammalian cells. 2010 Retrovirology Abstract HIV H69E 28 32 PR;PR 64;115 72;123 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. The results showed that the IN mutations H171A, L172A and EH170,1AA, located in the loop region 170EHLK173 between the alpha4 and alpha5 helices of IN, severely impaired the interaction with LEDGF/p75 but were still able to bind chromatin. 2010 Virology journal Abstract HIV H171A;L172A 41;48 46;53 IN;IN 28;148 30;150 20334344 Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir. By examining systematically all of the double mutants at the 140 and 148 positions, we demonstrate that only the combination G140S + Q148H is able to restore the catalytic properties of IN. 2010 Biochemistry Abstract HIV G140S;Q148H 125;133 130;138 IN 186 188 20334344 Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir. Clinical and virological data indicate the high relevance of the combination G140S + Q148H because of its limited impact on HIV replication and very high resistance to RAL. 2010 Biochemistry Abstract HIV G140S;Q148H 77;85 82;90 20334344 Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir. Finally, we show that the G140S-Q148H double mutant exhibits the highest resistance to RAL. 2010 Biochemistry Abstract HIV G140S;Q148H 26;32 31;37 20334344 Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir. Resistance to raltegravir (RAL), the first HIV-1 integrase (IN) inhibitor approved by the FDA, involves three genetic pathways: IN mutations N155H, Q148H/R/K, and Y143H/R/C. 2010 Biochemistry Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 141;148;148;148;163;163;163 146;157;157;157;172;172;172 IN;IN;IN 49;60;128 58;62;130 20334563 Short communication: selection of thymidine analogue resistance mutational patterns in children infected from a common HIV type 1 subtype G source. At first sampling date, the T215Y-linked pattern was observed in five cases and the T215F cluster was seen in nine. 2010 AIDS research and human retroviruses Abstract HIV T215F;T215Y 84;28 89;33 20334563 Short communication: selection of thymidine analogue resistance mutational patterns in children infected from a common HIV type 1 subtype G source. In HIV-1, thymidine analogue mutations (TAMs) cluster in one of two groups (215Y, 41L, 210W, or 215F, 219E/Q), representing two independent mutational patterns (T215Y and T215F cluster, respectively). 2010 AIDS research and human retroviruses Abstract HIV T215F;T215Y 171;161 176;167 20334563 Short communication: selection of thymidine analogue resistance mutational patterns in children infected from a common HIV type 1 subtype G source. The mutation T215Y reverted in three out of four patients who discontinued AZT/d4T treatment. 2010 AIDS research and human retroviruses Abstract HIV T215Y 13 18 20334563 Short communication: selection of thymidine analogue resistance mutational patterns in children infected from a common HIV type 1 subtype G source. Under AZT/d4T therapies, an association was found between the HLA B*13 (in combination with HLA DRB1*0701) and the mutation T215Y. 2010 AIDS research and human retroviruses Abstract HIV T215Y 124 129 20334563 Short communication: selection of thymidine analogue resistance mutational patterns in children infected from a common HIV type 1 subtype G source. We speculate that in the context of these subtype G viruses, the development of the T215Y mutation may be strongly disfavored whereas the presence of HLA B*13 may counteract this effect and permit its development. 2010 AIDS research and human retroviruses Abstract HIV T215Y 84 89 20334564 Ultrasensitive detection of minor drug-resistant variants for HIV after nevirapine exposure using allele-specific PCR: clinical significance. An allele-specific quantitative PCR (ASPCR) assay was used to quantify the pre-ART frequency of K103N and Y181C in 26 women who had received sdNVP. 2010 AIDS research and human retroviruses Abstract HIV K103N;Y181C 96;106 101;111 20334566 Short communication: high polymorphism rates in the HR1 and HR2 gp41 and presence of primary resistance-related mutations in HIV type 1 circulating in Brazil: possible impact on enfuvirtide efficacy. Other polymorphisms frequently detected were E137K (10% and 13.8%), L130I (8.8% and 9.2%), S129N (6.3% and 10.8%), L44M (2.5% and 4.6%), S138A (2.5% and 1.5%), and N43K (1.3% and 0%) in DNA and RNA, respectively. 2010 AIDS research and human retroviruses Abstract HIV E137K;L130I;L44M;N43K;S129N;S138A 45;68;115;164;91;137 50;73;119;168;96;142 20334566 Short communication: high polymorphism rates in the HR1 and HR2 gp41 and presence of primary resistance-related mutations in HIV type 1 circulating in Brazil: possible impact on enfuvirtide efficacy. We detected mutations related to enfuvirtide resistance (L44M or N43K) in HR1 DNA samples from three individuals (3.8%) and RNA samples from three individuals (4.6%). 2010 AIDS research and human retroviruses Abstract HIV L44M;N43K 57;65 62;69 20334569 Analysis of RT sequences of subtype C HIV-type 1 isolates from indian patients at failure of a first-line treatment according to clinical and/or immunological WHO guidelines. Numerous crucial DRMs to NRTIs and NNRTIs could be recorded including TAMs of pathway 1 and K65R. 2010 AIDS research and human retroviruses Abstract HIV K65R 92 96 NNRTI;NRTI 35;25 41;30 20334569 Analysis of RT sequences of subtype C HIV-type 1 isolates from indian patients at failure of a first-line treatment according to clinical and/or immunological WHO guidelines. We have observed a decrease of the polymorphism at positions 36 and 214 of RT while D121Y, V179I, and Q217E could be new DRMs. 2010 AIDS research and human retroviruses Abstract HIV D121Y;Q217E;V179I 84;102;91 89;107;96 RT 75 77 20334571 Genetic characterization analysis of the tat exon-1 region of HIV type 1 CRF07_BC strains in China. There were two conserved amino acid variations in the 1 approximately 56 aa fragment of tat gene exon-1 of 07_BC isolates, which were R7N (71.6%) and R46F (90.3%), as compared with subtype B' strains in Thailand. 2010 AIDS research and human retroviruses Abstract HIV R46F;R7N 150;134 154;137 Tat 88 91 20345882 HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy. CD4 percentage <15% prior to switching regimens [odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02-14.93] and plasma HIV RNA>5 log(10) copies/mL (OR 2.46; 95% CI 1.04-5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. 2010 HIV medicine Abstract HIV Q151M 258 263 20345882 HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. 2010 HIV medicine Abstract HIV K65R;M184I;M184V;Q151M 217;122;122;195 221;129;129;200 NRTI;NRTI 4;48 36;52 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. A fourth subject possessed a F673L substitution previously associated with 4E10 resistance. 2010 PloS one Abstract HIV F673L 29 34 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. In one case resistant virus carrying a W680G substitution was transmitted from mother to infant. 2010 PloS one Abstract HIV W680G 39 44 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Our third subject carried Envs with a W680R substitution causing variable resistance to 4E10, indicating that residues outside the MPER are required to confer the phenotype. 2010 PloS one Abstract HIV W680R 38 43 Env 26 30 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. We used site-directed mutagenesis to demonstrate that the W680G substitution is necessary for conferring the 4E10-resistant phenotype, but that it is not sufficient to transfer the phenotype to a 4E10-sensitive Env. 2010 PloS one Abstract HIV W680G 58 63 Env 211 214 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. One hundred copies of each patient's HIV-1 DNA were tested for NVP-resistance point-mutations (K103N, Y181C, and G190A) with a sensitive oligonucleotide ligation assay that was able to detect mutants even at low concentrations (> or = 5% of the viral population). 2010 Clinical infectious diseases Abstract HIV G190A;K103N;Y181C 113;95;102 118;100;107 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. RESULTS: At initiation of NVP-ART, resistance mutations were identified in 38 (26%) of 148 participants given sdNVP (K103N in 19 [13%], Y181C in 8 [5%], G190A in 28 [19%], and > or = 2 mutations in 15 [10%]), at a median 9.3 months after receipt of sdNVP. 2010 Clinical infectious diseases Abstract HIV G190A;K103N;Y181C 153;117;136 158;123;141 20377421 Short communication: Molecular epidemiology of HIV type 1 in the Republic of Dagestan, Russian Federation: virtually uniform circulation of subtype A, former Soviet Union variant, with predominance of the V77I(PR) subvariant. Forty (97.6%) of 41 samples were of subtype A, former Soviet Union variant (A(FSU)), of which 27 (67.5%) clustered with the subvariant containing the V77I substitution in protease (V77I(PR)). 2010 AIDS research and human retroviruses Abstract HIV V77I;V77I 150;181 154;186 PR;PR 171;186 179;188 20377421 Short communication: Molecular epidemiology of HIV type 1 in the Republic of Dagestan, Russian Federation: virtually uniform circulation of subtype A, former Soviet Union variant, with predominance of the V77I(PR) subvariant. The results, therefore, show the relationship of the HIV-1 epidemic in Dagestan with that of other areas of Russia and of neighboring countries, and reveal the spread of the A(FSU) V77I(PR) variant in the North Caucasus area. 2010 AIDS research and human retroviruses Abstract HIV V77I 179 185 PR 186 188 20377427 Natural polymorphisms of integrase among HIV type 1-infected South African patients. Amino acid sequence analysis revealed there were no primary mutations (Y143R/C/H, Q148H/R/K, and N155H/S) associated with reduced susceptibility to the integrase inhibitors raltegravir and elvitegravir. 2010 AIDS research and human retroviruses Abstract HIV N155H;N155S;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 97;97;82;82;82;71;71;71 104;104;91;91;91;80;80;80 IN 152 161 20377427 Natural polymorphisms of integrase among HIV type 1-infected South African patients. However, one sample had the T97A mutation, three samples had the E157Q and V165I mutations, and the majority of samples contained the polymorphic mutation V72I. 2010 AIDS research and human retroviruses Abstract HIV E157Q;T97A;V165I;V72I 65;28;75;155 70;32;80;159 20377427 Natural polymorphisms of integrase among HIV type 1-infected South African patients. However, the impact of E157Q and other naturally occurring polymorphisms warrants further phenotypic investigation. 2010 AIDS research and human retroviruses Abstract HIV E157Q 23 28 20377825 Highly active antiretroviral therapy improved persistent lamivudine-resistant viremia in acute hepatitis B virus genotype Ae infection with coinfection of human immunodeficiency virus. At that time, LAM-resistant HIV mutation, M184V, had been already detected. 2010 Hepatology research Abstract HIV M184V 42 47 20378550 Differential induction of interleukin-10 in monocytes by HIV-1 clade B and clade C Tat proteins. Additionally, the C31S mutation found in C Tat is responsible for the inability of these Tat proteins to produce high IL-10 levels in monocytes due to its inability to induce intracellular calcium flux through L-type calcium channels. 2010 The Journal of biological chemistry Abstract HIV C31S 18 22 Tat;Tat 43;89 46;92 20378550 Differential induction of interleukin-10 in monocytes by HIV-1 clade B and clade C Tat proteins. In this study, we show that the cysteine to serine mutation at position 31, found in >90% of HIV-1 clade C Tat proteins, results in a marked decrease in IL-10 production in monocytes compared with clade B Tat. 2010 The Journal of biological chemistry Abstract HIV C31S 32 74 Tat;Tat 107;205 110;208 20380480 Impact of low abundance HIV variants on response to ritonavir-boosted atazanavir or fosamprenavir given once daily with tenofovir/emtricitabine in antiretroviral-naive HIV-infected patients. In the four FPV/r-treated VFs, baseline HIV TAMs combinations and/or PI mutations were detected in one by PG at VF (RT: L210W + T215C; PR: M46I + L76V) and three others by CA alone (RT: L210W + T215Y; RT: M41L; RT: K65R + K70R; PR: I47V); all four had study drug-associated mutations (CA detecting more HIV-1 resistance mutations than PG). 2010 AIDS research and human retroviruses Abstract HIV I47V;K65R;K70R;L210W;L210W;L76V;M41L;M46I;T215C;T215Y 232;215;222;120;186;146;205;139;128;194 236;219;226;125;191;150;209;143;133;199 Capsid;Capsid;PI;PR;PR;RT;RT;RT;RT 172;285;69;135;228;116;182;201;211 174;287;71;137;230;118;184;203;213 20380480 Impact of low abundance HIV variants on response to ritonavir-boosted atazanavir or fosamprenavir given once daily with tenofovir/emtricitabine in antiretroviral-naive HIV-infected patients. In the three ATV/r VFs, no baseline drug-associated mutations were detected by PG; for one patient CA detected RT: K65R; PR: I84V. 2010 AIDS research and human retroviruses Abstract HIV I84V;K65R 125;115 129;119 Capsid;PR;RT 99;121;111 101;123;113 20382184 Drug-resistant mutation patterns in CRF01_AE cases that failed d4T+3TC+nevirapine fixed-dosed, combination treatment: Follow-up study from the Lampang cohort. CRF01_AE-specific polymorphisms were found in 19 residues, and GPOvir-failure cases had significantly higher frequency of N348I, E399D, P537S, and I542M. 2010 Antiviral research Abstract HIV E399D;I542M;N348I;P537S 129;147;122;136 134;152;127;141 20382184 Drug-resistant mutation patterns in CRF01_AE cases that failed d4T+3TC+nevirapine fixed-dosed, combination treatment: Follow-up study from the Lampang cohort. M184V lamivudine resistance was most frequent in both naive and exposed groups. 2010 Antiviral research Abstract HIV M184V 0 5 20382184 Drug-resistant mutation patterns in CRF01_AE cases that failed d4T+3TC+nevirapine fixed-dosed, combination treatment: Follow-up study from the Lampang cohort. The exposed group had predominantly thymidine analogue-related mutations, whereas the naive group had a higher prevalence of Q151M and K103N mutations. 2010 Antiviral research Abstract HIV K103N;Q151M 135;125 140;130 20382184 Drug-resistant mutation patterns in CRF01_AE cases that failed d4T+3TC+nevirapine fixed-dosed, combination treatment: Follow-up study from the Lampang cohort. The GPOvir-failure cases had not only known stavudine-, lamivudine- and nevirapine-resistant mutations, but also V118I, G196E, and H221Y. 2010 Antiviral research Abstract HIV G196E;H221Y;V118I 120;131;113 125;136;118 20384328 Accurate ensemble molecular dynamics binding free energy ranking of multidrug-resistant HIV-1 proteases. Multidrug resistance to lopinavir is enthalpically driven and increases through a decrease in the protein-ligand van der Waals interaction, principally due to the V82A/I84V mutation, and an increase in net electrostatic repulsion due to water-mediated disruption of protein-ligand interactions in the catalytic region. 2010 Journal of chemical information and modeling Abstract HIV I84V;V82A 168;163 172;167 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. BACKGROUND: Amdoxovir acts synergistically with zidovudine in vitro and the combination prevents or delays the selection of thymidine analogue and K65R mutations. 2010 Antiviral therapy Abstract HIV K65R 147 151 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. Associations between N348I and individual antiretroviral drug exposure were estimated using a matched case-control approach. 2010 Antiviral therapy Abstract HIV N348I 21 26 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. BACKGROUND: There is conflicting evidence on specific reverse transcriptase inhibitors to which the N348I mutation in the connection domain of HIV type-1 reverse transcriptase confers resistance. 2010 Antiviral therapy Abstract HIV N348I 100 105 RT;RT 54;154 75;175 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. Cases were defined as the first resistance test where N348I was detected; for each case, the 10 closest (in calendar time) N348N tests were selected as controls. 2010 Antiviral therapy Abstract HIV N348I;N348N 54;121 59;128 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. CONCLUSIONS: This is the first clinical evidence to suggest that efavirenz might select for N348I in addition to nevirapine, that stavudine might select for N348I in addition to zidovudine and that TDF might protect against the mutation. 2010 Antiviral therapy Abstract HIV N348I;N348I 92;157 97;162 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. Drugs that were statistically significantly positively associated with N348I were efavirenz (OR 1.55, 95% confidence interval [CI] 1.08-2.23; P=0.017) and nevirapine (OR 2.06, 95% CI 1.49-2.85; P<0.001). 2010 Antiviral therapy Abstract HIV N348I 71 76 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. Here, we examined associations between the emergence of N348I and antiretroviral history in a large clinical database. 2010 Antiviral therapy Abstract HIV N348I 56 61 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. RESULTS: N348I was detected in 198 (8.7%) cases. 2010 Antiviral therapy Abstract HIV N348I 9 14 20386075 Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data. Tenofovir disoproxil fumarate (TDF) was significantly negatively associated (OR 0.27, 95% CI 0.15-0.48; P<0.001) with N348I. 2010 Antiviral therapy Abstract HIV N348I 118 123 20388636 HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens. Four different patterns of IN mutations were observed: (i) emergence of Q148H/R with secondary mutations (n=5 patients); (ii) emergence of N155H, then replaced by a pattern including Y143C/H/R (n=3); (iii) selection of S230N (n=1); and (iv) no evidence of selection of IN mutations (n=2). 2010 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148R;S230N;Y143C;Y143H;Y143R 139;72;72;219;183;183;183 144;79;79;224;192;192;192 IN;IN 27;269 29;271 20388636 HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens. The median plasma raltegravir Cmin was lower in patients with selection of the N155H mutation followed by Y143C/H/R compared with patients with Q148H/R and with patients without emerging mutations or without VF. 2010 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148R;Y143C;Y143H;Y143R 79;144;144;106;106;106 84;151;151;115;115;115 20388636 HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens. The median raltegravir and elvitegravir fold changes (FCs) were 244 (154-647) and 793 (339-892), respectively, for the Q148H/R pattern, while the median raltegravir and elvitegravir FCs were 21 (6-52) and 3 (2-3), respectively, with Y143C/H/R. 2010 The Journal of antimicrobial chemotherapy Abstract HIV Q148H;Q148R;Y143C;Y143H;Y143R 119;119;233;233;233 126;126;242;242;242 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Addition of the nucleoside resistance mutations L74V or M41L+T215Y to K101E+G190S improved fitness and abolished EFV-dependent stimulation of replication. 2010 Virology Abstract HIV G190S;K101E;L74V;M41L;T215Y 76;70;48;56;61 81;75;52;60;66 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. D10, a clinical RT backbone containing M41L+T215Y and K101E+G190S, also demonstrated EFV-dependent stimulation that was dependent on the presence of K101E. 2010 Virology Abstract HIV G190S;K101E;K101E;M41L;T215Y 60;54;149;39;44 65;59;154;43;49 RT 16 18 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K101E+G190S reduced fitness in the absence of EFV and increased EFV resistance, compared to either single mutant. 2010 Virology Abstract HIV G190S;K101E 6;0 11;5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Unexpectedly, K101E+G190S also replicated more efficiently in the presence of EFV than in its absence. 2010 Virology Abstract HIV G190S;K101E 20;14 25;19 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We measured the effects of non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutations K101E+G190S, on replication fitness and EFV-resistance of HIV(NL4-3). 2010 Virology Abstract HIV G190S;K101E 105;99 110;104 NNRTI;RT 27;65 63;67 20400170 Increased sensitivity of HIV variants selected by attachment inhibitors to broadly neutralizing antibodies. Based on these observations, we propose that although F423Y, I595F and K655E may all affect the presentation of the 2F5 and 4E10 epitopes, natural immune mimicry is rare only for the I595F effect. 2010 Virology Abstract HIV F423Y;I595F;I595F;K655E 54;61;183;71 59;66;188;76 20400170 Increased sensitivity of HIV variants selected by attachment inhibitors to broadly neutralizing antibodies. Thus, it seems that in addition to restricting AI resistance development, incorporation of I595F into an appropriate vehicle could elicit a novel antiviral response to improve vaccine efficacy. 2010 Virology Abstract HIV I595F 91 96 20400170 Increased sensitivity of HIV variants selected by attachment inhibitors to broadly neutralizing antibodies. We also observed that I595F did not substantially increase envelope sensitivity to HIV-infected patient sera. 2010 Virology Abstract HIV I595F 22 27 Env 59 67 HIV infections 83 95 20400170 Increased sensitivity of HIV variants selected by attachment inhibitors to broadly neutralizing antibodies. We report on three such mutations: F423Y (gp120 CD4 binding pocket) and I595F and K655E (gp41 ectodomain). 2010 Virology Abstract HIV F423Y;I595F;K655E 35;72;82 40;77;87 gp120;gp41 42;89 47;93 20404123 HIV-1 protease codon 36 polymorphisms and differential development of resistance to nelfinavir, lopinavir, and atazanavir in different HIV-1 subtypes. Sequence analysis of the protease gene at week 35 revealed that the major NFV resistance mutation D30N emerged in NFV-selected subtype B viruses and in I36 subtype C viruses, despite polymorphic variation. 2010 Antimicrobial agents and chemotherapy Abstract HIV D30N 98 102 PR 25 33 20404123 HIV-1 protease codon 36 polymorphisms and differential development of resistance to nelfinavir, lopinavir, and atazanavir in different HIV-1 subtypes. The presence of I47A in LPV-selected I36 CRF02_AG virus conferred higher-level resistance than L76V in LPV-selected M36 CRF02_AG virus. 2010 Antimicrobial agents and chemotherapy Abstract HIV I47A;L76V 16;95 20;99 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. BVM susceptibility was maintained by SP1-Q6A, -Q6H and -T8A mutations. 2010 Retrovirology Abstract HIV Q6H;T8A;Q6A 47;56;41 50;59;44 SP1 37 40 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. However, an SP1-V7A mutation conferred high-level BVM resistance, and SP1-V7M and T8Delta mutations conferred intermediate levels of BVM resistance. 2010 Retrovirology Abstract HIV V7A;V7M 16;74 19;77 SP1;SP1 12;70 15;73 20410281 Generation of infectious feline immunodeficiency virus (FIV) encoding FIV/human immunodeficiency virus chimeric protease. Chimeric PRs encoding combinations of the I37V, N55M, M56I, V59I, L97T, I98P, Q99V, and P100N mutations were cloned into FIV Gag-Pol, and those constructs that best approximated the temporal cleavage pattern generated by wild-type FIV PR, while maintaining HIV-like inhibitor specificity, were selected. 2010 Journal of virology Abstract HIV I37V;I98P;L97T;M56I;N55M;P100N;Q99V;V59I 42;72;66;54;48;88;78;60 46;76;70;58;52;93;82;64 GagPol;PR;PR 125;9;235 132;12;237 20410281 Generation of infectious feline immunodeficiency virus (FIV) encoding FIV/human immunodeficiency virus chimeric protease. However, a mutant PR with six substitutions (I37V, N55M, V59I, I98P, Q99V, and P100N) was selected and placed in the context of full-length FIV-34TF10. 2010 Journal of virology Abstract HIV I37V;I98P;N55M;P100N;Q99V;V59I 45;63;51;79;69;57 49;67;55;84;73;61 PR 18 20 20410281 Generation of infectious feline immunodeficiency virus (FIV) encoding FIV/human immunodeficiency virus chimeric protease. The residue at the position of one of the six mutations, I98P, further mutated on passage to either P98H or P98S. 2010 Journal of virology Abstract HIV I98P;P98H;P98S 57;100;108 61;104;112 20410281 Generation of infectious feline immunodeficiency virus (FIV) encoding FIV/human immunodeficiency virus chimeric protease. Two mutations, M56I and L97T, were intolerant to change and caused inefficient cleavage at NC-p2. 2010 Journal of virology Abstract HIV L97T;M56I 24;15 28;19 NC 91 93 20421122 Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. In addition, mutations Q148K and N155H were selected. 2010 Virology Abstract HIV N155H;Q148K 33;23 38;28 20421122 Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. Mechanisms by which N155H, Q148H/K/R, Y143R and E92Q confer resistance are proposed based on a structural model of integrase. 2010 Virology Abstract HIV E92Q;N155H;Q148H;Q148K;Q148R;Y143R 48;20;27;27;27;38 52;25;36;36;36;43 IN 115 124 20421122 Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. Mutation Q148R arose in four out of six raltegravir-selected resistant viruses. 2010 Virology Abstract HIV Q148R 9 14 20421122 Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. Q148H/K/R and N155H conferred resistance to raltegravir, but only minor changes in susceptibility to MK-2048. 2010 Virology Abstract HIV N155H;Q148H;Q148K;Q148R 14;0;0;0 19;9;9;9 20421122 Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. V54I, a previously unreported mutation, selected with raltegravir, was identified as a possible compensation mutation. 2010 Virology Abstract HIV V54I 0 4 20427524 A low-molecular-weight entry inhibitor of both CCR5- and CXCR4-tropic strains of human immunodeficiency virus type 1 targets a novel site on gp41. Escape variants of HIV-1(NL4-3) were selected, and all resistant viruses were found to contain a common G514R (HxB2 numbering) mutation in Env, located proximal to the furin cleavage site in the fusion peptide of gp41. 2010 Journal of virology Abstract HIV G514R 104 109 gp41;Env 213;139 217;142 20427524 A low-molecular-weight entry inhibitor of both CCR5- and CXCR4-tropic strains of human immunodeficiency virus type 1 targets a novel site on gp41. Resistance via G514R is shown to be associated with enhancement of virion infectivity by PF-68742 that may result from altered properties of inhibitor-bound Env, rather than from a loss of compound binding. 2010 Journal of virology Abstract HIV G514R 15 20 Env 157 160 20427524 A low-molecular-weight entry inhibitor of both CCR5- and CXCR4-tropic strains of human immunodeficiency virus type 1 targets a novel site on gp41. When introduced into wild-type NL4-3 gp41, G514R conferred resistance to PF-68742. 2010 Journal of virology Abstract HIV G514R 43 48 gp41 37 41 20432620 Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. Again, responses with mTNF-K90R were higher than with gp120 alone. 2010 Die Pharmazie Abstract HIV K90R 27 31 gp120 54 59 20432620 Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. Furthermore, mTNF-K90R induced anti-gp120 IgA responses in nasal as well as vaginal washes from immunized mice, although these were not administration sites. 2010 Die Pharmazie Abstract HIV K90R 18 22 gp120 36 41 20432620 Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. Here, we evaluated the potential of mTNF-K90R as a mucosal vaccine adjuvant for the induction of systemic and mucosal immune responses against HIV. 2010 Die Pharmazie Abstract HIV K90R 41 45 20432620 Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. Nasal immunization of BALB/c mice with 5 microg of an HIV gp120 env protein immunogen together with mTNF-K90R induced higher serum anti-HIV gp120 protein immunoglobulin G (IgG) responses than gp120 alone. 2010 Die Pharmazie Abstract HIV K90R 105 109 gp120;gp120;gp120;Env 58;140;192;64 63;145;197;67 20432620 Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. These results indicate that mTNF-K90R may be applicable as amucosal adjuvant for HIV vaccination to induce both systemic and mucosal immune responses. 2010 Die Pharmazie Abstract HIV K90R 33 37 20432620 Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. We have previously reported that a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, possessed strong mucosal vaccine adjuvant activities in mice. 2010 Die Pharmazie Abstract HIV K90R 88 92 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. An FC of 2 was observed only for IN Y143R in the strand transfer assay. 2010 PloS one Abstract HIV Y143R 36 41 IN 33 35 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL. 2010 PloS one Abstract HIV N155H;Y143C;Y143R 73;82;82 78;89;89 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. 2010 PloS one Abstract HIV N155H;Y143C;Y143H;Y143R 21;76;76;76 26;85;85;85 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Wild-type (WT) IN and IN with mutations Y143C or Y143R were assayed in vitro in 3'end-processing, strand transfer and concerted integration assays. 2010 PloS one Abstract HIV Y143C;Y143R 40;49 45;54 IN;IN 15;22 17;24 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. With 3'end-processing assay, IC(50) were 0.4 microM, 0.9 microM (FC = 2.25) and 1.2 microM (FC = 3) for WT, IN Y143C and IN Y143R, respectively. 2010 PloS one Abstract HIV Y143C;Y143R 111;124 116;129 IN;IN 108;121 110;123 20438081 Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design. Crystal structures were determined with wild-type and K103N HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278). 2010 Journal of medicinal chemistry Abstract HIV K103N 54 59 RT 66 87 20438081 Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design. These structures reveal a similar binding mode for TMC125 and TMC278, whether bound to wild-type or K103N RT. 2010 Journal of medicinal chemistry Abstract HIV K103N 100 105 RT 106 108 20438763 Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino-terminal heptad repeat. Among these substitutions, N126K and/or E137Q conferred resistance to not only N36, but also C34, which is the corresponding C-HR-derived peptide fusion inhibitor. 2010 Antiviral research Abstract HIV E137Q;N126K 40;27 45;32 20438763 Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino-terminal heptad repeat. Denaturing experiments revealed that the stability of the 6-helix bundle of N126K/E137Q is greater than in the wild-type. 2010 Antiviral research Abstract HIV E137Q;N126K 82;76 87;81 20438763 Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino-terminal heptad repeat. The structure of the 6-helix bundle with N126K/E137Q was identical to that in wild-type HIV-1 except for the presence of a new hydrogen bond. 2010 Antiviral research Abstract HIV E137Q;N126K 47;41 52;46 20438763 Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino-terminal heptad repeat. These results suggest that the stabilizing effect of N126K/E137Q provides resistance to N36 and C34. 2010 Antiviral research Abstract HIV E137Q;N126K 59;53 64;58 20438763 Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino-terminal heptad repeat. This HIV-1 acquired a total of four amino acid substitutions, D36G, N126K and E137Q in gp41, and P183Q in gp120. 2010 Antiviral research Abstract HIV D36G;E137Q;N126K;P183Q 62;78;68;97 66;83;73;102 gp120;gp41 106;87 111;91 20438763 Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino-terminal heptad repeat. We performed crystallographic and biochemical analysis of the 6-helix bundle formed by synthetic gp41-derived peptides containing the N126K/E137Q substitutions. 2010 Antiviral research Abstract HIV E137Q;N126K 140;134 145;139 gp41 97 101 20439612 Novel protease inhibitors (PIs) containing macrocyclic components and 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane that are potent against multi-PI-resistant HIV-1 variants in vitro. At passage 50 with GRL-216 (the HIV isolate selected with GRL-216 at up to 0.16 microM [HIV216-0.16 microM]), HIV-1NL4-3 containing the L10I, L24I, M46L, V82I, and I84V mutations remained relatively sensitive to PIs, including darunavir, with the EC50s being 3- to 8-fold-greater than the EC50 of each drug for HIV-1NL4-3. 2010 Antimicrobial agents and chemotherapy Abstract HIV I84V;L10I;L24I;M46L;V82I 164;136;142;148;154 168;140;146;152;158 PI 212 215 20444482 Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection. In subjects expressing HLA-B*57/5801 and infected with the wild-type virus, the T242N escape appeared at 203 days (196-231) p/s, reached dominance at 277 days (265-315 days) p/s, and became complete at 323 days (289-373 days) p/s. 2010 Virology Abstract HIV T242N 80 85 20444482 Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection. The study highlights the differential selection of T242N escape by HLA-B*57 and B*5801 and suggests that the presence of HLA-B*57/5801-mediated immune pressure is able to control replication of the wild-type virus encoding Thr at Gag residue 242 but fails to suppress the T242N escape variant. 2010 Virology Abstract HIV T242N;T242N 51;272 56;277 Gag 230 233 20450778 [Evolution of HIV-1 drug resistance in patients failing combination antiretroviral therapy]. K103N, G190A, Y181C, K101P, M184V, D67N, K70R, T215Y and K219 were most common mutations. 2010 Zhonghua yi xue za zhi Abstract HIV D67N;G190A;K101P;K70R;M184V;T215Y;Y181C;K103N 35;7;21;41;28;47;14;0 39;12;26;45;33;52;19;5 20453629 Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa. M184V/I, K103N and V106A/M were the most common mutations. 2010 AIDS (London, England) Abstract HIV K103N;M184I;M184V;V106A;V106M 9;0;0;19;19 14;7;7;26;26 20455467 [CD4+ and CD8+ T-lymphocyte counts in human immunodeficiency virus type 1 subtype A-infected patients carrying mutations V77I in protease and/or A62V in reverse transcriptase]. According to the presence or absence of mutations V77I in protease and/or A62V in reverse transcriptase, the patients were divided into 2 study groups. 2010 Voprosy virusologii Abstract HIV A62V;V77I 74;50 78;54 RT;PR 82;58 103;66 20455467 [CD4+ and CD8+ T-lymphocyte counts in human immunodeficiency virus type 1 subtype A-infected patients carrying mutations V77I in protease and/or A62V in reverse transcriptase]. Immunological study showed that the median CD4+, CD8+, and CD4/CD8 in the patients infected with virus variants containing mutations V77I and/or A62V were increased by 25, 20, and 16%, respectively. 2010 Voprosy virusologii Abstract HIV A62V;V77I 145;133 149;137 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Many clusters had Y181C plus a non-major etravirine RAM; few had more than one major etravirine RAM. 2010 The Journal of antimicrobial chemotherapy Abstract HIV Y181C 18 23 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Of the 17 reported etravirine resistance-associated mutations (RAMs), Y181C/I/V, L100I, K101P and M230L were considered major based on published in vitro susceptibility data. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K101P;L100I;M230L;Y181C;Y181I;Y181V 88;81;98;70;70;70 93;86;103;79;79;79 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. RESULTS: Efavirenz preferentially selected for 16 mutations, including L100I (14% versus 0.1%, P < 0.001), K101P (3.3% versus 0.4%, P < 0.001) and M230L (2.8% versus 1.3%, P = 0.004), whereas nevirapine preferentially selected for 12 mutations, including Y181C/I/V (48% versus 6.9%, P < 0.001). 2010 The Journal of antimicrobial chemotherapy Abstract HIV K101P;L100I;M230L;Y181C;Y181I;Y181V 107;71;147;255;255;255 112;76;152;264;264;264 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Twenty-nine pairs of NNRTI-selected mutations covaried significantly, including Y181C with seven other mutations (A98G, K101E/H, V108I, G190A/S and H221Y), L100I with K103N, and K101P with K103S. 2010 The Journal of antimicrobial chemotherapy Abstract HIV A98G;G190A;G190S;H221Y;K101E;K101H;K101P;K103N;K103S;L100I;V108I;Y181C 114;136;136;148;120;120;178;167;189;156;129;80 118;143;143;153;127;127;183;172;194;161;134;85 NNRTI 21 26 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Two pairs (Y181C + V179F and Y181C + G190S) were predicted to confer >10-fold decreased etravirine susceptibility. 2010 The Journal of antimicrobial chemotherapy Abstract HIV G190S;V179F;Y181C;Y181C 37;19;11;29 42;24;17;34 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Viruses with three or more NNRTI-selected mutations often contained Y181C in combination with one or more minor etravirine RAMs; however, phenotypic and clinical correlates for most of these higher order combinations have not been published. 2010 The Journal of antimicrobial chemotherapy Abstract HIV Y181C 68 73 NNRTI 27 32 20471372 Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex. Recently, G48V mutation is found to co-exist with the mutation C95F in AIDS patients treated with saquinavir. 2010 Biochemical and biophysical research communications Abstract HIV C95F;G48V 63;10 67;14 AIDS 71 75 20471372 Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex. The mutation G48V in HIV-1 protease is a major resistance mutation against the drug saquinavir. 2010 Biochemical and biophysical research communications Abstract HIV G48V 13 17 PR 27 35 20471372 Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex. The present structure also provides a rationale for the clinical observation that the resistance mutations C95F/G48V/V82A occur as a cluster in AIDS patients. 2010 Biochemical and biophysical research communications Abstract HIV C95F;G48V;V82A 107;112;117 111;116;121 AIDS 144 148 20471372 Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex. We report here the three-dimensional crystal structure of G48V/C95F tethered HIV-1 protease/saquinavir complex. 2010 Biochemical and biophysical research communications Abstract HIV C95F;G48V 63;58 67;62 PR 83 91 20479206 Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors. A novel mutation, E92G, although rarely found in minority quasispecies, showed elvitegravir resistance. 2010 Antimicrobial agents and chemotherapy Abstract HIV E92G 18 22 20479206 Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors. Secondary mutations, such as T97A and G140S, found rarely and only as minority quasispecies, were present in the elvitegravir-resistant clones. 2010 Antimicrobial agents and chemotherapy Abstract HIV G140S;T97A 38;29 43;33 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. For these 11 Envs, I309L did not alter replication in primary CD4 T cells; however, replication in monocyte-derived macrophages was enhanced. 2010 Virology Abstract HIV I309L 19 24 Env 13 17 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Infection of cell lines with low CD4 or CCR5 revealed that I309L enhanced utilization of CD4 but did not affect the ability to use CCR5. 2010 Virology Abstract HIV I309L 59 64 20504942 Enhanced exposure of human immunodeficiency virus type 1 primary isolate neutralization epitopes through binding of CD4 mimetic compounds. At passage 21 in the presence of 50 microM NBD-556, two amino acid substitutions (S375N in C3 and A433T in C4) were identified. 2010 Journal of virology Abstract HIV A433T;S375N 98;82 103;88 20504942 Enhanced exposure of human immunodeficiency virus type 1 primary isolate neutralization epitopes through binding of CD4 mimetic compounds. On the other hand, in the selection with sCD4, seven mutations (E211G, P212L, V255E, N280K, S375N, G380R, and G431E) appeared during the passages. 2010 Journal of virology Abstract HIV E211G;G380R;G431E;N280K;P212L;S375N;V255E 64;99;110;85;71;92;78 69;104;115;90;76;97;83 20516562 Genotypic and phenotypic evolution of HIV type-1 protease during in vitro sequential or concomitant combination of atazanavir and amprenavir. By contrast, addition of APV to I50L-containing recombinant viruses was not associated with reversion. 2010 Antiviral therapy Abstract HIV I50L 32 36 20516562 Genotypic and phenotypic evolution of HIV type-1 protease during in vitro sequential or concomitant combination of atazanavir and amprenavir. METHODS: Recombinant viruses containing in vitro and in vivo selected I50L and I50V proteases were constructed and cultured in increasing concentrations of APV or ATV, respectively. 2010 Antiviral therapy Abstract HIV I50L;I50V 70;79 74;83 PR 84 93 20516562 Genotypic and phenotypic evolution of HIV type-1 protease during in vitro sequential or concomitant combination of atazanavir and amprenavir. Phenotypically, both sequential and concomitant ATV-APV pressure yielded viruses resistant to all the drugs tested, although the emergence of I50L by ATV pressure on APV-resistant variants was associated with a reduced resistance to APV and darunavir. 2010 Antiviral therapy Abstract HIV I50L 142 146 20516562 Genotypic and phenotypic evolution of HIV type-1 protease during in vitro sequential or concomitant combination of atazanavir and amprenavir. RESULTS: ATV or APV alone selected I50L- or I50V-containing variants. 2010 Antiviral therapy Abstract HIV I50L;I50V 35;44 39;48 20516562 Genotypic and phenotypic evolution of HIV type-1 protease during in vitro sequential or concomitant combination of atazanavir and amprenavir. Subsequent addition of ATV to I50V-containing recombinant viruses led to the reversion of this change and the later selection of I50L. 2010 Antiviral therapy Abstract HIV I50L;I50V 129;30 133;34 20516562 Genotypic and phenotypic evolution of HIV type-1 protease during in vitro sequential or concomitant combination of atazanavir and amprenavir. The different pathways select for isoleucine or leucine at position 50, whereas the I50V mutation was excluded. 2010 Antiviral therapy Abstract HIV I50V 84 88 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. CONCLUSIONS: Mutants with K65R and M184V linked on the same genome were the most common HIV-1 variants in samples analysed from patients failing TNV, ddI and 3TC with both mutations detected by standard genotype. 2010 Antiviral therapy Abstract HIV K65R;M184V 26;35 30;40 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. METHODS: Single genome sequencing was performed on 9 failure samples containing both K65R and M184V mutations by standard genotype, either as wild-type/mutant mixtures (6/9) or as mutant only (3/9). 2010 Antiviral therapy Abstract HIV K65R;M184V 85;94 89;99 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Phenotypic testing of recombinant clones showed a significant increase in resistance for double mutants: mean fold resistance to abacavir, ddI and TNV was 6.5, 4.3 and 1.6 for K65R/M184V double mutants versus 2.5, 1.9 and 0.6 for M184V single mutants, respectively (P<0.001). 2010 Antiviral therapy Abstract HIV K65R;M184V;M184V 176;181;230 180;186;235 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. RESULTS: Of the 204 single genome sequences analysed, 50% were K65R/M184V double mutants, 38% were M184V single mutants, 10% were M184I single mutants and only 1% (2 sequences) were K65R single mutants. 2010 Antiviral therapy Abstract HIV K65R;K65R;M184I;M184V;M184V 63;182;130;68;99 67;186;135;73;104 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Furthermore, heat-inactivated, inhibitor-treated, or W34A/K63A Pin1 causes an attenuated in vitro uncoating of the HIV-1 core. 2010 The Journal of biological chemistry Abstract HIV K63A;W34A 58;53 62;57 PI 63 65 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The mutant virus S16A/P17A shows a severely attenuated HIV-1 replication and an impaired reverse transcription. 2010 The Journal of biological chemistry Abstract HIV P17A;S16A 22;17 26;21 RT 89 110 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The S16A/P17A change increased the amount of particulate CA cores in the cytosol of target cells and correlated with the restriction of HIV-1 infection. 2010 The Journal of biological chemistry Abstract HIV P17A;S16A 9;4 13;8 Capsid 57 59 HIV infections 136 151 20530477 N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. Here we demonstrate that RNase H-mediated primer removal is indeed more efficient in the presence of NNRTIs; however, the N348I mutant enzyme is able to counteract this effect. 2010 The Journal of biological chemistry Abstract HIV N348I 122 127 NNRTI 101 107 20530477 N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. N348I has been associated with resistance to the non-nucleoside RT inhibitor (NNRTI), nevirapine; however, a possible mechanism that links changes in RNase H activity to changes in NNRTI susceptibility remains to be established. 2010 The Journal of biological chemistry Abstract HIV N348I 0 5 NNRTI;NNRTI;RT 78;181;64 83;186;66 20530477 N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. The data are in agreement with clinical data, which demonstrate a stronger effect of N348I on susceptibility to nevirapine as compared with efavirenz. 2010 The Journal of biological chemistry Abstract HIV N348I 85 90 20530477 N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. These findings provide strong evidence to suggest that N348I can thwart the inhibitory effects of nevirapine during initiation of (+)-strand DNA synthesis, which provides a novel mechanism for resistance. 2010 The Journal of biological chemistry Abstract HIV N348I 55 60 20530477 N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. We have recently demonstrated that the N348I mutation in the connection domain causes selective dissociation from RNase H-competent complexes, whereas the functional integrity of the polymerase-competent complex remains largely unaffected. 2010 The Journal of biological chemistry Abstract HIV N348I 39 44 Pol 183 193 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. 3 (2.1%) subjects had both multiple TAMs+M184V, and all experienced VF. 2010 PloS one Abstract HIV M184V 36 46 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Of 9 (6.4%) subjects with M184V/I (7 at <20% levels), 6 experienced VF. 2010 PloS one Abstract HIV M184I;M184V 26;26 33;33 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. Each of the NAIM analogs display potent activity against wild-type recombinant purified HIV-1 RT as well as RTs containing the K103N or Y181C resistance mutations. 2010 Letters in drug design & discovery Abstract HIV K103N;Y181C 127;136 132;141 RT;RT 94;108 96;111 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Additionally, K65A and K65R mutants displayed a further decrease in mismatch extension efficiency, primarily at the level of dNTP binding. 2010 Journal of molecular biology Abstract HIV K65A;K65R 14;23 18;27 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. K65R mutation did not greatly increase misinsertion fidelity, but K65A mutation led to higher incorporation fidelity. 2010 Journal of molecular biology Abstract HIV K65A;K65R 66;0 70;4 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. We now examine this hypothesis in pre-steady-state kinetic studies using wild-type human immunodeficiency virus-1 RT and two substitution mutants, K65A and K65R. 2010 Journal of molecular biology Abstract HIV K65A;K65R 147;156 151;160 RT 114 116 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. We showed previously that a 5-amino-acid deletion spanning Lys65 and a K65A substitution both enhanced the fidelity of dNTP insertion. 2010 Journal of molecular biology Abstract HIV K65A 71 75 20538456 Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses. Notably, the series retains potency against the K103N/Y181C and Y188L mutants, among others. 2010 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C;Y188L 48;54;64 53;59;69 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Although UDPS of plasma samples from 18 subtype C and 27 subtype B viruses showed that a higher proportion of subtype C viruses contain K65R (1.04% vs. 0.25%; p<0.001), limiting dilution clonal sequencing failed to corroborate its presence in two of the samples in which K65R was present in >1.5% of UDPS reads. 2010 PloS one Abstract HIV K65R;K65R 271;136 275;140 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. BACKGROUND: The HIV-1 nucleoside RT inhibitor (NRTI)-resistance mutation, K65R confers intermediate to high-level resistance to the NRTIs abacavir, didanosine, emtricitabine, lamivudine, and tenofovir; and low-level resistance to stavudine. 2010 PloS one Abstract HIV K65R 74 78 NRTI;NRTI;RT 47;132;33 51;137;35 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. CONCLUSIONS: This study shows that the RT KKK nucleotide template in subtype C viruses can lead to the spurious detection of K65R by highly sensitive PCR-dependent sequencing techniques. 2010 PloS one Abstract HIV K65R 125 129 RT 39 41 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. However, the study is also consistent with the subtype C nucleotide template being inherently responsible for increased polymerization-induced K65R mutations in vivo. 2010 PloS one Abstract HIV K65R 143 147 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. METHODS AND FINDINGS: We performed ultra-deep pyrosequencing (UDPS) and clonal dideoxynucleotide sequencing of plasma virus samples to assess the prevalence of minority K65R variants in subtype B and C viruses from untreated individuals. 2010 PloS one Abstract HIV K65R 169 173 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Several lines of evidence suggest that K65R is more common in HIV-1 subtype C than subtype B viruses. 2010 PloS one Abstract HIV K65R 39 43 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. We therefore performed UDPS on clones and site-directed mutants containing subtype B- and C-specific patterns of silent mutations in the conserved KKK motif encompassing RT codons 64 to 66 and found that subtype-specific nucleotide differences were responsible for increased PCR-induced K65R mutation in subtype C viruses. 2010 PloS one Abstract HIV K65R 287 291 RT 170 172 20541446 Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. Among patients who do not respond to treatment with the PI nelfinavir (NFV), the D30N mutation is often observed. 2010 Journal of molecular graphics & modelling Abstract HIV D30N 81 85 PI 56 58 20541446 Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. D30N appears to facilitate conformational changes in subtype B PR, but not in that from subtype C, and this could be associated with disestablishment of an alpha-helical region of the PR. 2010 Journal of molecular graphics & modelling Abstract HIV D30N 0 4 PR;PR 63;184 65;186 20541446 Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. However, several reports have shown that D30N emerges with different frequencies in distinct HIV-1 genetic forms or subtypes. 2010 Journal of molecular graphics & modelling Abstract HIV D30N 41 45 20541446 Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. The compensatory mutations N83T and N88D, observed in vitro and in vivo when subtype C acquires D30N, were also studied. 2010 Journal of molecular graphics & modelling Abstract HIV D30N;N83T;N88D 96;27;36 100;31;40 20541446 Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations. The wild-type and drug-resistant D30N mutants were investigated in both subtypes. 2010 Journal of molecular graphics & modelling Abstract HIV D30N 33 37 20541566 Tissue culture drug resistance analysis of a novel HIV-1 protease inhibitor termed PL-100 in non-B HIV-1 subtypes. One of these involved the V82A and L90M resistance mutations while the other involved a mutation at position T80I, with other mutations being observed at positions M46I/L, I54M, K55R, L76F, P81S and I85V. 2010 Antiviral research Abstract HIV I54M;I85V;K55R;L76F;L90M;M46I;M46L;P81S;T80I;V82A 172;199;178;184;35;164;164;190;109;26 176;203;182;188;39;170;170;194;113;30 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3 (K101E) and RTMDR. 2010 Bioorganic & medicinal chemistry letters Abstract HIV K101E 150 155 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. Two drug-resistant protease variants FLAP+ (L10I, G48V, I54V, V82A) and ACT (V82T, I84V) decrease the binding affinity with DRV by 1.0 kcal/mol and 1.6 kcal/mol respectively. 2010 Journal of chemical theory and computation Abstract HIV G48V;I54V;I84V;L10I;V82A;V82T 50;56;83;44;62;77 54;60;87;48;66;81 PR 19 27 20547806 Baseline genotypic and phenotypic susceptibilities of HIV-1 group O to enfuvirtide. The N42D resistance-associated mutation in the gp41 region was detected in 98% of cases. 2010 Antimicrobial agents and chemotherapy Abstract HIV N42D 4 8 gp41 47 51 20547806 Baseline genotypic and phenotypic susceptibilities of HIV-1 group O to enfuvirtide. Thus, despite the natural genotypic resistance conferred by the N42D signature mutation, HIV-O variants appear to be phenotypically susceptible. 2010 Antimicrobial agents and chemotherapy Abstract HIV N42D 64 68 20558207 Evaluation of HIV-1 integrase inhibitors on human primary macrophages using a luciferase-based single-cycle phenotypic assay. IN inhibitors were also tested using a lentiviral vector containing an IN with introduced T66I/S153Y mutations, known to affect the activity of azido-group-containing diketo acid (DKA) IN inhibitors. 2010 Journal of virological methods Abstract HIV S153Y;T66I 95;90 100;94 IN;IN;IN 0;71;185 2;73;187 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. The most frequent mutations were M184V (n = 11), conferring resistance to lamivudine and emtricitabine, and Y181C (n = 4), G190A/S (n = 4) and K103N (n = 4), conferring resistance to NNRTIs. 2010 The Journal of antimicrobial chemotherapy Abstract HIV G190A;G190S;K103N;M184V;Y181C 123;123;143;33;108 130;130;148;38;113 NNRTI 183 189 20578491 Virologic and immunologic outcomes in HIV-infected Cambodian children after 18 months of highly active antiretroviral therapy (HAART). Genotypic resistance typing in 2 children with PVL > 400 copies/ml at 18 months demonstrated mutations associated with resistance to lamivudine (M184V) and non-nucleoside reverse transcriptase inhibitors (Y181C and G190A). 2010 The Southeast Asian journal of tropical medicine and public health Abstract HIV G190A;M184V;Y181C 215;145;205 220;150;211 NNRTI 156 192 20587857 HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. Mutations V82A/F/T/S/M/I were primarily selected by the administration of ritonavir (RTV) in an historical ARV regimen. 2010 Antiviral therapy Abstract HIV V82A;V82F;V82I;V82M;V82S;V82T 10;10;10;10;10;10 24;24;24;24;24;24 20587857 HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. RESULTS: In protease (PR), resistance-associated mutations M46I/L, I54M/L/V/A/S and V82A/F/T/S/M/I were associated with each other and with minor mutations at codons 10, 24 and 71. 2010 Antiviral therapy Abstract HIV I54A;I54L;I54M;I54S;I54V;M46I;M46L;V82A;V82F;V82I;V82M;V82S;V82T 67;67;67;67;67;59;59;84;84;84;84;84;84 79;79;79;79;79;65;65;98;98;98;98;98;98 PR;PR 12;22 20;24 20587857 HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. The non-nucleoside K103N+L100I mutations were observed at high frequency (15.5%) and were significantly associated with the nucleoside mutation L74V in BF recombinants. 2010 Antiviral therapy Abstract HIV K103N;L100I;L74V 19;25;144 24;30;148 20587857 HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. The results provide clinical evidence of a molecular interaction between K103N+L100I and L74V mutations at the reverse transcriptase gene in vivo, limiting the future use of second-generation non-nucleoside reverse transcriptase inhibitors such as etravirine. 2010 Antiviral therapy Abstract HIV K103N;L100I;L74V 73;79;89 78;84;93 NNRTI;RT 192;111 228;132 20588166 The effect of transmitted HIV-1 drug resistance on pre-therapy viral load. DISCUSSION: Our study provides clear evidence of an in-vivo fitness cost associated with the M184V/I mutation independent of drug effects which select for this mutation. 2010 AIDS (London, England) Abstract HIV M184I;M184V 93;93 100;100 20588166 The effect of transmitted HIV-1 drug resistance on pre-therapy viral load. However, patients harbouring M184V/I (n = 61) had a significantly lower viral load [adjusted mean difference -0.33 log10 copies/ml (95% CI -0.54 to -0.11), 53% lower (95% CI 22 to 71%), P = 0.002] compared to wild-type virus. 2010 AIDS (London, England) Abstract HIV M184I;M184V 29;29 36;36 20592075 Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions. In conclusion, severe defects in RNase H activity alone, exemplified by the P236L mutant, appear sufficient to cause a substantial reduction in fitness. 2010 Journal of virology Abstract HIV P236L 76 81 20592075 Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions. K103N and Y181C mutants had normal RNase H activity; V106A, G190A, and G190S mutants had moderate reductions in activity; and the P236L mutant had substantially reduced activity. 2010 Journal of virology Abstract HIV G190A;G190S;P236L;V106A;Y181C;K103N 60;71;130;53;10;0 65;76;135;58;15;5 20592075 Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions. K103N and Y181C viruses had fitness similar to that of the wild type while V106A, G190A, G190S, and P236L viruses had reduced fitness. 2010 Journal of virology Abstract HIV G190A;G190S;P236L;V106A;Y181C;K103N 82;89;100;75;10;0 87;94;105;80;15;5 20592075 Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions. We measured the fitness of six NNRTI-resistant mutants, the K103N, V106A, Y181C, G190A, G190S, and P236L viruses, using a flow cytometry-based cell culture assay. 2010 Journal of virology Abstract HIV G190A;G190S;K103N;P236L;V106A;Y181C 81;88;60;99;67;74 86;93;65;104;72;79 NNRTI 31 36 20592075 Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions. With the exception of the P236L mutant, reduced fitness correlates with low virion-associated polymerization efficiency and reduced RT content. 2010 Journal of virology Abstract HIV P236L 26 31 RT 132 134 20598556 Hybrid diarylbenzopyrimidine non-nucleoside reverse transcriptase inhibitors as promising new leads for improved anti-HIV-1 chemotherapy. It also proved more active against mutant L100I, K103N, Y188L, and K103N+Y181C RT HIV-1 strains than efavirenz. 2010 Bioorganic & medicinal chemistry Abstract HIV K103N;K103N;L100I;Y181C;Y188L 49;67;42;73;56 54;72;47;78;61 RT 79 81 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. First, the hexamer was stabilized by engineering disulfide cross-links (either A14C/E45C or A42C/T54C) between the N-terminal domains of adjacent subunits. 2010 Journal of molecular biology Abstract HIV A14C;A42C;E45C;T54C 79;92;84;97 83;96;88;101 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Second, the cross-linked hexamers were prevented from polymerizing further into hyperstable capsid-like structures by mutations (W184A and M185A) that interfered with dimeric association between the C-terminal domains that link adjacent hexamers. 2010 Journal of molecular biology Abstract HIV M185A;W184A 139;129 144;135 Capsid 92 98 20600301 Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R. CONCLUSIONS: In virologically failing patients due to K65R- and other non-thymidine-mutations, simple regimen intensification with zidovudine resulted in sustained HIV-1 suppression. 2010 The Journal of infection Abstract HIV K65R 54 58 20600301 Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R. METHODS: We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. 2010 The Journal of infection Abstract HIV K65R 193 197 HIV infections 23 37 20600301 Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R. OBJECTIVES: The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations. 2010 The Journal of infection Abstract HIV K65R 52 56 RT;RT;RT 16;39;129 37;41;131 20600301 Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R. RT-sequence revealed mutations at position K65R in combination with other non-TAMs. 2010 The Journal of infection Abstract HIV K65R 43 47 RT 0 2 20608080 [Prediction of the efficacy of bevirimat used for the treatment of HIV infection in Russia]. The nucleotide sequences coding the CA-SP1 Pr55(gag) in 61 samples of HIV-1 subtype A variant IDU-A isolated in Russia were analyzed for bevirimat resistance mutations (CA-H226V, CA-L231F, CA-231M, SP1-A1V, SP1-A3T, SP1-A3V) and for polymorphisms in the GAG CA-SP1 cleavage site. 2010 Voprosy virusologii Abstract HIV A1V;H226V;L231F;A3T;A3V 202;172;182;211;220 205;177;187;214;223 SP1;SP1;SP1;SP1;SP1;Gag;Gag;Capsid;Capsid;Capsid;Capsid;Capsid 39;198;207;216;261;48;254;36;169;179;189;258 42;201;210;219;264;51;257;38;171;181;191;260 20608080 [Prediction of the efficacy of bevirimat used for the treatment of HIV infection in Russia]. The substitution SP-T8Q was observed in 98% of cases, which could probably affect the clinical efficacy of bevirimat. 2010 Voprosy virusologii Abstract HIV T8Q 20 23 20608080 [Prediction of the efficacy of bevirimat used for the treatment of HIV infection in Russia]. There were three polymorphisms CA-G225S, CA-R229K, CA-V2301 and a high variability in the C-terminus of SP1. 2010 Voprosy virusologii Abstract HIV G225S;R229K 34;44 39;49 SP1;Capsid;Capsid;Capsid 104;31;41;51 107;33;43;53 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Although the G116E substitution occurred during long-term cultivation of human cells infected with NL-4/5S6/7SvifS, the viruses with G116E unexpectedly became resistant to CM, but not human TRIM5 alpha-mediated restriction. 2010 Retrovirology Abstract HIV G116E;G116E 13;133 18;138 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Sequence analysis of the CA region of the adapted virus revealed a G-to-E substitution at the 116 th position of the CA (G116E). 2010 Retrovirology Abstract HIV G116E 121 126 Capsid;Capsid 25;117 27;119 20610719 Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. G118R also reduced viral replication capacity to approximately 1% that of the isogenic wild-type (wt) virus. 2010 Journal of virology Abstract HIV G118R 0 5 20610719 Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. G118R, which appeared first in cell culture, conferred low levels of resistance to MK-2048. 2010 Journal of virology Abstract HIV G118R 0 5 20610719 Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. Here, we report the identification of mutations (G118R and E138K) which confer resistance to MK-2048 and not to RAL or EVG. 2010 Journal of virology Abstract HIV E138K;G118R 59;49 64;55 20610719 Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. The subsequent selection of E138K partially restored replication capacity to approximately 13% of wt levels and increased resistance to MK-2048 to approximately 8-fold. 2010 Journal of virology Abstract HIV E138K 28 33 20610719 Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. Viruses containing G118R and E138K remained largely susceptible to both RAL and EVG, suggesting a unique interaction between this second-generation INSTI and the enzyme may be defined by these residues as a potential basis for the increased intrinsic affinity and longer "off" rate of MK-2048. 2010 Journal of virology Abstract HIV E138K;G118R 29;19 34;24 INSTI 148 153 20610954 Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. Of note, the P225H and A71V are 'minor' drug-resistance mutations conferring only minimal drug-resistance phenotypes in the absence of major mutations. 2010 AIDS (London, England) Abstract HIV A71V;P225H 23;13 27;18 20610954 Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. The prevalence of nonnucleoside transcriptase inhibitor mutations was 74%, with P225H present in 55% of study specimens. 2010 AIDS (London, England) Abstract HIV P225H 80 85 20610954 Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. The prevalence of nucleoside transcriptase inhibitor mutations was 76%, with M184V and L74V present in 60 and 38% of samples, respectively. 2010 AIDS (London, England) Abstract HIV L74V;M184V 87;77 91;82 20610954 Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. The prevalence of protease inhibitor mutations was 45%, with major mutation L90M seen in 33% and minor mutation A71V in 36% of samples. 2010 AIDS (London, England) Abstract HIV A71V;L90M 112;76 116;80 PR 18 26 20617924 Effect of host genetics on the development of cytomegalovirus retinitis in patients with AIDS. RESULTS: In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22- 31.54; P = .03) to CMV retinitis. 2010 The Journal of infectious diseases Abstract HIV I224V;S420L 304;123 309;128 20624074 Genetic characterization of HIV type 1 among patients with suspected immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy in Kenya. These included nucleoside reverse transcriptase inhibitor (RTI) mutations: M41L, K65R, D67N, K70R, M184V, and K219Q, and nonnucleoside RTI mutations: K101P, L100I, K103N, and Y181C. 2010 AIDS research and human retroviruses Abstract HIV D67N;K101P;K103N;K219Q;K65R;K70R;L100I;M184V;M41L;Y181C 87;150;164;110;81;93;157;99;75;175 91;155;169;115;85;97;162;104;79;180 NRTI;RT;RT 15;59;135 47;62;138 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. CONCLUSIONS: With this highly sensitive UDPS protocol preexisting drug resistance was infrequently observed; only M184I, T215A and T215I were detected at very low levels. 2010 PloS one Abstract HIV M184I;T215A;T215I 114;121;131 119;126;136 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. During treatment failure, M184V replaced M184I and dominated the population in combination with T215Y, while wild-type variants were rarely detected. 2010 PloS one Abstract HIV M184I;M184V;T215Y 41;26;96 46;31;101 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In four of five pre-treatment samples low levels (0.07-0.09%) of the M184I mutation were observed. 2010 PloS one Abstract HIV M184I 69 74 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Other resistance mutations, except T215A and T215I were below the detection limit. 2010 PloS one Abstract HIV T215A;T215I 35;45 40;50 20631150 Divergent evolution in reverse transcriptase (RT) of HIV-1 group O and M lineages: impact on structure, fitness, and sensitivity to nonnucleoside RT inhibitors. In contrast to observations showing acquired drug resistance associated with fitness loss, the C181Y mutation in the C181 group O lineage resulted in a loss of intrinsic NNRTI resistance and was accompanied by fitness loss. 2010 Journal of virology Abstract HIV C181Y 95 100 NNRTI 170 175 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Fitness was partially restored by the presence of additional RAL resistance mutations at positions G140S and E92Q or E138K, respectively. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;E92Q;G140S 117;109;99 122;113;104 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In the absence of drug, RAL-resistant mutants were less fit than wild type, and the Q148H mutant was significantly less fit than the N155H mutant. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N155H;Q148H 133;84 138;89 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In the presence of RAL, the N155H mutant remained fitter than the Q148H mutant, but the G140S/Q148H double mutant was fitter than single mutants or the E92Q/N155H double mutant. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E92Q;G140S;N155H;N155H;Q148H;Q148H 152;88;157;28;94;66 156;93;162;33;99;71 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The N155H mutants emerge first, and are eventually replaced by Q148H mutants, usually in combination with G140S. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G140S;N155H;Q148H 106;4;63 111;9;68 20636277 Comparison of protease inhibitor (PI) resistance-associated mutations between PI-naive and PI-experienced HIV-1 infected patients in Thailand where subtype A/E is predominant. The most common primary PI-RAMs in the latter group were V82A (10%), I54V (7%) and G48V (4.8%). 2010 Current HIV research Abstract HIV G48V;I54V;V82A 83;69;57 87;73;61 PI 24 26 20636277 Comparison of protease inhibitor (PI) resistance-associated mutations between PI-naive and PI-experienced HIV-1 infected patients in Thailand where subtype A/E is predominant. The most common secondary PI-RAMs in both groups were M36I (91%), H69K (34%) and L89M (30%). 2010 Current HIV research Abstract HIV H69K;L89M;M36I 66;81;54 70;85;58 PI 26 28 20640812 Structural basis for the resilience of Darunavir (TMC114) resistance major flap mutations of HIV-1 protease. Good affinity of Darunavir accounts for the additive effects of well accommodation at binding site, good ligand-receptor electrostatic and van der waals energy while, the low susceptibility to I50V and I54M can be rationalized in terms of flexibility in the binding site residues that do not permit drug accommodation to the binding site distortions created by the mutation. 2009 Interdisciplinary sciences, computational life sciences Abstract HIV I50V;I54M 193;202 197;206 20640812 Structural basis for the resilience of Darunavir (TMC114) resistance major flap mutations of HIV-1 protease. Our research indicates that the observed effectiveness of Darunavir against the wild type HIV-1 protease is due to an extremely high affinity towards the wild-type and a relatively mild effect to the I50V and I54M mutations is due to low affinity towards the inhibitor. 2009 Interdisciplinary sciences, computational life sciences Abstract HIV I50V;I54M 200;209 204;213 PR 96 104 20640812 Structural basis for the resilience of Darunavir (TMC114) resistance major flap mutations of HIV-1 protease. The major flap mutations I50V and I54M lower the binding affinity of Darunavir by altering the position of binding site residues in 3D space. 2009 Interdisciplinary sciences, computational life sciences Abstract HIV I50V;I54M 25;34 29;38 20647908 HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays. CONCLUSION: Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. 2010 AIDS (London, England) Abstract HIV E92Q;N155H 161;126 165;131 IN 63 72 20647908 HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays. METHODS: We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. 2010 AIDS (London, England) Abstract HIV E92Q;E92Q;N155H;N155H 139;156;161;145 143;160;166;150 IN;IN 65;191 74;200 20647908 HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays. RESULTS: Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations. 2010 AIDS (London, England) Abstract HIV E92Q;N155H 70;75 74;80 IN;IN;IN 19;140;224 28;149;233 20649426 Effect of acyclovir on HIV-1 set point among herpes simplex virus type 2-seropositive persons during early HIV-1 infection. V75I and other mutations in HIV-1 reverse transcriptase reported from in vitro acyclovir studies were not observed. 2010 The Journal of infectious diseases Abstract HIV V75I 0 4 RT 34 55 20655872 Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. Even though the A18H Vpu mutant forms rimantadine sensitive proton channels, the binding of drug and its influence on the protein structure appears to be very different from that for the M2 proteins. 2011 Biochimica et biophysica acta Abstract HIV A18H 16 20 Vpu 21 24 20655872 Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. Similarly, Vpu does not normally bind rimantadine, but the single site mutation A18H converts a non-specific channel to a selective proton channel that is sensitive to rimantadine. 2011 Biochimica et biophysica acta Abstract HIV A18H 80 84 Vpu 11 14 20660190 The effect of clade-specific sequence polymorphisms on HIV-1 protease activity and inhibitor resistance pathways. AE protease has been observed to develop resistance through a nonactive-site N88S mutation in response to nelfinavir (NFV) therapy, whereas clade B protease develops both the active-site mutation D30N and the nonactive-site mutation N88D. 2010 Journal of virology Abstract HIV D30N;N88D;N88S 196;233;77 200;237;81 PR;PR 3;148 11;156 20660190 The effect of clade-specific sequence polymorphisms on HIV-1 protease activity and inhibitor resistance pathways. The D30N/N88D mutations in clade B resulted in a significant loss of affinity for NFV and, to a lesser extent, for DRV. 2010 Journal of virology Abstract HIV D30N;N88D 4;9 8;13 20660190 The effect of clade-specific sequence polymorphisms on HIV-1 protease activity and inhibitor resistance pathways. This weaker affinity may lead to the nonactive-site N88S variant in AE, which exhibits significantly decreased affinity for both NFV and DRV. 2010 Journal of virology Abstract HIV N88S 52 56 20660667 Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. A major problem with the first approved NNRTIs was the emergence of mutations in the HIV-1 reverse transcriptase (RT), in particular K103N and Y181C, which led to resistance to the entire class. 2010 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 133;143 138;148 RT;NNRTI;RT 91;40;114 112;46;116 20660676 HIV-1 protease mutations and protease inhibitor cross-resistance. Of the mutations with the greatest effect on PI susceptibility, I84AV was associated with decreased susceptibility to eight PIs; V32I, G48V, I54ALMSTV, V82F, and L90M were associated with decreased susceptibility to six to seven PIs; I47A, G48M, I50V, L76V, V82ST, and N88S were associated with decreased susceptibility to four to five PIs; and D30N, I50L, and V82AL were associated with decreased susceptibility to fewer than four PIs. 2010 Antimicrobial agents and chemotherapy Abstract HIV D30N;G48M;G48V;I47A;I50L;I50V;I54A;I54L;I54M;I54S;I54T;I54V;I84A;I84V;L76V;L90M;N88S;V32I;V82A;V82F;V82L;V82S;V82T 345;240;135;234;351;246;141;141;141;141;141;141;64;64;252;162;269;129;361;152;361;258;258 349;244;139;238;355;250;150;150;150;150;150;150;69;69;256;166;273;133;366;156;366;263;263 PI;PI;PI;PI;PI 45;124;229;336;432 47;127;232;339;435 20666602 HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy. A360V was not associated with specific drug combinations and was found to emerge later than M184V or thymidine analogue mutations. 2010 Clinical infectious diseases Abstract HIV M184V;A360V 92;0 97;5 20666602 HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy. N348I correlated with M184V and predominantly occurred in patients receiving lamivudine and zidovudine concomitantly. 2010 Clinical infectious diseases Abstract HIV M184V;N348I 22;0 27;5 20666602 HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy. RESULTS: The connection domain mutations N348I, R356K, R358K, A360V, and A371V were more frequently observed in ART-exposed than ART-naive patients, of which only N348I and A360V were nonpolymorphic (with a prevalence of <1.5% in untreated patients). 2010 Clinical infectious diseases Abstract HIV A360V;A360V;A371V;N348I;N348I;R356K;R358K 62;173;73;41;163;48;55 67;178;78;46;168;53;60 20668070 Estimating frequencies of minority nevirapine-resistant strains in chronically HIV-1-infected individuals naive to nevirapine by using stochastic simulations and a mathematical model. Here, we employ stochastic simulations and a mathematical model to estimate the frequencies of strains carrying different combinations of the common nevirapine resistance mutations K103N, V106A, Y181C, Y188C, and G190A in chronically infected HIV-1 patients naive to nevirapine. 2010 Journal of virology Abstract HIV G190A;K103N;V106A;Y181C;Y188C 213;181;188;195;202 218;186;193;200;207 20685117 Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported. 2010 Bioorganic & medicinal chemistry letters Abstract HIV E92Q;G140S;N155H;Q148H 139;124;133;118 143;129;138;123 20686027 Long-term restriction by APOBEC3F selects human immunodeficiency virus type 1 variants with restored Vif function. Tandem stop mutations K26X and H27X in human immunodeficiency virus type 1 (HIV-1) vif compromise virus replication in human T-cell lines that stably express APOBEC3F (A3F) or APOBEC3G (A3G). 2010 Journal of virology Abstract HIV H27X;K26X 31;22 35;26 Vif 83 86 20686411 Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring. CONCLUSIONS: A high rate of acquisition of TAMs, but not of K65R, among patients with prolonged viraemia was observed. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 60 64 20686411 Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring. K65R was detected in 8 of 63 (13%) patients and was negatively associated with number of TAMs (P = 0.01) but not viral subtype (P = 0.30). 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 0 4 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Mutation to smaller side chains eliminated hydrophobic interactions in the PR(I50V) and PR(I54V) structures. 2010 The FEBS journal Abstract HIV I50V;I54V 78;91 82;95 PR;PR 75;88 77;90 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Substitution of the larger side chains in PR(V32I) , PR(I54M) and PR(L90M) resulted in the formation of new hydrophobic contacts with flap residues, residues 79 and 80, and Asp25, respectively. 2010 The FEBS journal Abstract HIV I54M;L90M;V32I 56;69;45 60;73;49 Asp;PR;PR;PR 173;42;53;66 176;44;55;68 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. The observed structural changes in PR(I84V)-APV, PR(V32I)-APV and PR(I50V)-APV were related to their reduced inhibition by APV of six-, 10- and 30-fold, respectively, relative to wild-type PR. 2010 The FEBS journal Abstract HIV I50V;I84V;V32I 69;38;52 73;42;56 PR;PR;PR;PR 35;49;66;189 37;51;68;191 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. The PR(I84V)-APV complex had lost hydrophobic contacts with APV, the PR(V32I)-APV complex showed increased hydrophobic contacts within the hydrophobic cluster and the PR(I50V) complex had weaker polar and hydrophobic interactions with APV. 2010 The FEBS journal Abstract HIV I50V;I84V;V32I 170;7;72 174;11;76 PR;PR;PR 4;69;167 6;71;169 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. The structural and kinetic effects of amprenavir (APV), a clinical HIV protease (PR) inhibitor, were analyzed with wild-type enzyme and mutants with single substitutions of V32I, I50V, I54V, I54M, I84V and L90M that are common in drug resistance. 2010 The FEBS journal Abstract HIV I50V;I54M;I54V;I84V;L90M;V32I 179;191;185;197;206;173 183;195;189;201;210;177 PR;PR 71;81 79;83 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Finally, this 3TC sensitizing effect of the cPPT inactivation of the M184I vector was reversed by elevating the dCTP level, but not by the other three dNTPs. 2010 Virology Abstract HIV M184I 69 74 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. First, the HIV-1 M184I mutant vector displays reduced transduction efficiency compared to wild type (WT) RT vector, which could be rescued by both elevating the cellular dNTP concentration and incorporating WT RT molecules into the M184I vector particles. 2010 Virology Abstract HIV M184I 232 237 RT;RT 105;210 107;212 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Second, the central polypurine tract (cPPT) mutation and M184I mutation additively reduced the vector transduction to almost undetectable levels, particularly in nondividing cells. 2010 Virology Abstract HIV M184I 57 62 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. These data support a mechanistic interaction between cPPT and M184I RT with respect to viral replication and sensitivity to 3TC. 2010 Virology Abstract HIV M184I 62 67 RT 68 70 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Third, the M184I (-) cPPT vector became significantly more sensitive to 3TC than the M184I (+) cPPT vector, but not to AZT or Nevirapine in the dividing cells. 2010 Virology Abstract HIV M184I;M184I 11;85 16;90 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. We recently reported that the M184I 3TC resistant mutation reduces RT binding affinity to dNTP substrates. 2010 Virology Abstract HIV M184I 30 35 RT 67 69 20702624 Mutation at a single position in the V2 domain of the HIV-1 envelope protein confers neutralization sensitivity to a highly neutralization-resistant virus. Our results suggest that the D179N mutation induces a conformational change that exposes epitopes in both the gp120 and the gp41 portions of the envelope protein, such as the CD4 binding site and the MPER, that are normally concealed by conformational masking. 2010 Journal of virology Abstract HIV D179N 29 34 Env;gp120;gp41 145;110;124 153;115;128 20707733 Transmission of drug-resistant HIV type 1 strains in HAART-naive patients: a 5-year retrospective study in Sicily, Italy. DRAMs to nonnucleoside reverse transcriptase inhibitors (nNRTI) were detected most frequently [11/108 (10.2%)], of which K103N was the most prevalent (4.6%), whereas the prevalence of DRAMs was lowest for protease inhibitors (PI) [3/108 (2.8%)]. 2010 AIDS research and human retroviruses Abstract HIV K103N 121 126 NNRTI;PR;NNRTI;PI 9;205;57;226 44;213;62;228 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. The in vitro assays showed that the D64V point mutation in the catalytic domain of HIV-1 integrase efficiently inhibited the integration of the transgene upon vector transduction, while the targeting specificity of the vector to preferentially transduce and mediate durable expression in DCs was maintained. 2010 Vaccine Abstract HIV D64V 36 40 IN 89 98 20713171 Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors. Drug susceptibility showed G335D, A371V, or both did not confer resistance by themselves but conferred significant resistance to NRTIs with TAMs, especially in mutants containing G335D, A371V and TAM type 2. 2010 Microbes and infection Abstract HIV A371V;A371V;G335D;G335D 34;186;27;179 39;191;32;184 NRTI 129 134 20713171 Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors. In the C-terminal half, G335D (100%), N348I (36.8%), A371V (100%), A376S (5.3%) and A400T (97.4%) were detected, although G335D, A371V and A400T were considered polymorphisms of CRF01_AE. 2010 Microbes and infection Abstract HIV A371V;A371V;A376S;A400T;A400T;G335D;G335D;N348I 53;129;67;84;139;24;122;38 58;134;72;89;144;29;127;43 20713171 Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors. Subsequently, we assessed the impact of CRF01_AE polymorphisms G335D and A371V with or without thymidine analogue mutations (TAMs) on susceptibility to NRTI with recombinant viruses. 2010 Microbes and infection Abstract HIV A371V;G335D 73;63 78;68 NRTI 152 156 20718620 HIV type 1 pol gene diversity and genotypic antiretroviral drug resistance mutations in Malabo, Equatorial Guinea. Analysis of antiretroviral drug resistance mutations revealed two patients each harboring one major mutation, M46I in protease and D67N in reverse transcriptase sequences, respectively. 2010 AIDS research and human retroviruses Abstract HIV D67N;M46I 131;110 135;114 RT;PR 139;118 160;126 20722751 Long-term follow-up of 11 protease inhibitor (PI)-naive and PI-treated HIV-infected patients harbouring virus with insertions in the HIV-1 protease gene. The insertions were mainly located between codons 33 and 39 and associated with surrounding mutations (M36I/L and R41K). 2011 HIV medicine Abstract HIV M36I;M36L;R41K 103;103;114 110;110;118 20729708 Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals. Among these mutations, the lamivudine drug-resistance-associated mutation M184I in reverse transcriptase was detected in 25% of clones in the absence of any lamivudine exposure. 2010 AIDS (London, England) Abstract HIV M184I 74 79 RT 83 104 20729708 Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals. In our population, among pretreated patients, 72% of K22H viruses versus 42% in WT K22 viruses harbored at least two drug-resistance-associated mutations in a GA/GG dinucleotide context. 2010 AIDS (London, England) Abstract HIV K22H 53 57 20729708 Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals. In-vitro experiments showed that mutant K22H failed to completely neutralize APOBEC3G. 2010 AIDS (London, England) Abstract HIV K22H 40 44 20729708 Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals. More specifically, K22H viruses harbored significantly more G16E and M36I in protease than in those isolated from pretreated patients harboring WT K22 viruses. 2010 AIDS (London, England) Abstract HIV G16E;K22H;M36I 60;19;69 64;23;73 PR 77 85 20729708 Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals. Mutation K22H in Vif was more frequent in patients failing to antiretroviral compared to antiretroviral-naive patients. 2010 AIDS (London, England) Abstract HIV K22H 9 13 Vif 17 20 20729708 Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals. Upon infection of MT-2 cells, most of the K22H proviral clones encoded increased numbers of G-to-A mutations. 2010 AIDS (London, England) Abstract HIV K22H 42 46 20733040 Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure. Here, we demonstrate that in the presence of zidovudine, HIV-1(BH10) RT mutations P272A/R277K/T286A produce a significant reduction of the viral replication capacity in peripheral blood mononuclear cells in both the absence and presence of M41L/T215Y. 2010 Antimicrobial agents and chemotherapy Abstract HIV P272A;R277K;T286A;M41L;T215Y 82;88;94;240;245 87;93;99;244;250 RT 69 71 20739898 Different evolution of genotypic resistance profiles to emtricitabine versus lamivudine in tenofovir-containing regimens. CONCLUSIONS: Our study shows lower rates of M184V development in FTC + TDF regimens versus 3TC + TDF and suggests a potential role of boosted protease inhibitors and TDF in delaying the M184V emergence. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;M184V 44;186 49;191 PR 142 150 20739898 Different evolution of genotypic resistance profiles to emtricitabine versus lamivudine in tenofovir-containing regimens. In vitro selection experiments and docking analysis show that other reverse transcriptase (RT) mutations, even localized in RT connection domain, can be selected by 3TC + TDF or FTC + TDF in M184V absence and can affect RT affinity for 3TC/FTC and/or TDF. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 191 196 RT;RT;RT;RT 68;91;124;220 89;93;126;222 20739898 Different evolution of genotypic resistance profiles to emtricitabine versus lamivudine in tenofovir-containing regimens. Multivariable analysis shows that factors correlated with a lower probability of M184V emergence at failure were the use of FTC compared with 3TC [odds ratio (OR): 0.32 (95% confidence interval (CI): 0.10 to 0.99), P = 0.04], the use of boosted protease inhibitor, and the use of TDF [OR: 0.20 (95% CI: 0.11 to 0.37), P < 0.001, and OR: 0.47 (95%CI: 0.22 to 1.01), P = 0.05, respectively]. 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 81 86 PR 245 253 20739898 Different evolution of genotypic resistance profiles to emtricitabine versus lamivudine in tenofovir-containing regimens. RESULTS: The M184V mutation is less prevalent in FTC + TDF-treated patients than in 3TC + TDF-treated, and 3TC-treated/TDF-naive patients (14.3% versus 40.0%, P = 0.01 and 55.6%, P < 0.001). 2010 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 13 18 2078407 Conservative mutations in the putative metal-binding region of human immunodeficiency virus tat disrupt virus replication. However, cysteine-to-glycine at position 34 affected tat stability. 1990 AIDS research and human retroviruses Abstract HIV C34G 9 43 Tat 53 56 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Notably, MK-2048 is equally potent against wild-type IN and raltegravir-resistant IN mutant N155H, suggesting this inhibitor may bind similarly within their drug-binding pockets. 2010 Biochemistry Abstract HIV N155H 92 97 IN;IN 53;82 55;84 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Studies of raltegravir-resistant IN mutants N155H and Q148H without inhibitors demonstrated that their capacity to assemble the synaptic complex and promote concerted integration was similar to their reported virus replication capacities. 2010 Biochemistry Abstract HIV N155H;Q148H 44;54 49;59 IN 33 35 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The concerted integration activity of Q148H showed a higher cross-resistance to raltegravir than observed with N155H, providing evidence as to why the Q148H pathway with secondary mutations is the predominant pathway upon prolonged treatment. 2010 Biochemistry Abstract HIV N155H;Q148H;Q148H 111;38;151 116;43;156 20805392 Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors. F227C and Y181C were the major mutations selected by MK-4965 in subtype A and C viruses during resistance selection. 2010 Antimicrobial agents and chemotherapy Abstract HIV Y181C;F227C 10;0 15;5 20805392 Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors. In subtype B viruses, on the other hand, known NNRTI-associated mutations (e.g., Y181C, P236L, L100I, V179D, and K103N) were selected by the NNRTIs. 2010 Antimicrobial agents and chemotherapy Abstract HIV K103N;L100I;P236L;V179D;Y181C 113;95;88;102;81 118;100;93;107;86 NNRTI;NNRTI 47;141 52;147 20805392 Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors. With efavirenz (EFV), F227C and V106M were the major mutations responsible for viral breakthrough in subtype A viruses, whereas a single pathway (G190A/V106M) accounted for mutation development in subtype C viruses. 2010 Antimicrobial agents and chemotherapy Abstract HIV G190A;F227C;V106M;V106M 146;22;152;32 151;27;157;37 20805392 Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors. Y181C was the dominant mutation in the resistance selection with etravirine (ETV) in subtype A, and E138K/H221Y were the mutations detected in the breakthrough viruses from subtype C viruses with ETV. 2010 Antimicrobial agents and chemotherapy Abstract HIV E138K;H221Y;Y181C 100;106;0 105;111;5 20805393 Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. Common partner mutations included M46I, I54V, V82A, I84V, and L90M. 2010 Antimicrobial agents and chemotherapy Abstract HIV I54V;I84V;L90M;M46I;V82A 40;52;62;34;46 44;56;66;38;50 20805393 Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir. 2010 Antimicrobial agents and chemotherapy Abstract HIV L76V 0 4 20805393 Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. Of 20,501 sequences with >=1 PI RAM, 3.2% contained L76V; L76V was alone in 0.04%. 2010 Antimicrobial agents and chemotherapy Abstract HIV L76V;L76V 52;58 56;62 PI 29 31 20805393 Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs) and effects on PI susceptibility associated with the L76V mutation were studied in a large database. 2010 Antimicrobial agents and chemotherapy Abstract HIV L76V 134 138 PR;PI;PI 18;38;96 26;40;98 20810731 Early selection in Gag by protective HLA alleles contributes to reduced HIV-1 replication capacity that may be largely compensated for in chronic infection. Additional mutations in Gag that may modulate the impact of the T242N mutation on RC were identified. 2010 Journal of virology Abstract HIV T242N 64 69 Gag 24 27 20810731 Early selection in Gag by protective HLA alleles contributes to reduced HIV-1 replication capacity that may be largely compensated for in chronic infection. However, RC correlated positively with the presence of known compensatory mutations in chronic viruses from B*57-expressing individuals harboring the Gag T242N mutation (n = 50; R = 0.36; P = 0.01), suggesting that the rescue of fitness defects occurred through mutations at secondary sites. 2010 Journal of virology Abstract HIV T242N 154 159 Gag 150 153 20810732 In vitro selection of highly darunavir-resistant and replication-competent HIV-1 variants by using a mixture of clinical HIV-1 isolates resistant to multiple conventional protease inhibitors. The H219Q and I223V substitutions in Gag, lacking in HIV-1(C(P51)), likely contributed to conferring a replication advantage on HIV-1(MIX(P51)) by reducing intravirion cyclophilin A content. 2010 Journal of virology Abstract HIV H219Q;I223V 4;14 9;19 Gag 37 40 20817922 Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors. M154I and V165I IN polymorphisms occurred at a frequency of 6% in untreated patients, reaching 21.3% and 13.4%, respectively, in antiretroviral-treated patients. 2010 The Journal of antimicrobial chemotherapy Abstract HIV V165I;M154I 10;0 15;5 IN 16 18 20817922 Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors. Similarly, V165I and G163R mutations were associated with the RT resistance mutations F227L and M230L, respectively, and the T206S polymorphism was associated with the RT resistance mutation L210W. 2010 The Journal of antimicrobial chemotherapy Abstract HIV F227L;G163R;L210W;M230L;T206S;V165I 86;21;191;96;125;11 91;26;196;101;130;16 RT;RT 62;168 64;170 20817922 Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors. The mutation M154L, absent in drug-naive patients, was prevalent at 5.7% in antiretroviral-treated patients, and was positively associated with RT resistance mutations F227L and T215Y. 2010 The Journal of antimicrobial chemotherapy Abstract HIV F227L;M154L;T215Y 168;13;178 173;18;183 RT 144 146 20818500 Frequency and diversity of human immunodeficiency virus type 1 mutations associated with antiretroviral resistance among patients from Southern Brazil failing highly active antiretroviral therapy (HAART). Mutations associated with resistance to protease inhibitor (PI) were detected in 124 tests (97.6%), the main ones were L90M in 28 (22.0%), V82A in 27 (21.2%), M46I in 26 (20.5%), and I54V in 23 (18.1%). 2010 International journal of molecular medicine Abstract HIV I54V;L90M;M46I;V82A 183;119;159;139 187;123;163;143 PR;PI 40;60 48;62 20818500 Frequency and diversity of human immunodeficiency virus type 1 mutations associated with antiretroviral resistance among patients from Southern Brazil failing highly active antiretroviral therapy (HAART). The main mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance were M184V in 82 (64.6%), and the thymidine analog mutations were D67N in 51 (40.1%) tests, K70R in 45 (35.4%), T215Y in 40 (31.5%), and M41L in 38 (30.0%). 2010 International journal of molecular medicine Abstract HIV D67N;K70R;M184V;M41L;T215Y 162;188;101;233;208 166;192;106;237;213 NRTI;NRTI 35;79 67;83 20818500 Frequency and diversity of human immunodeficiency virus type 1 mutations associated with antiretroviral resistance among patients from Southern Brazil failing highly active antiretroviral therapy (HAART). The most frequent major mutations associated with resistance to non-nucleoside RT inhibitors (NNRTI) were K103N in 47 (37.0%), G190A in 11 (8.7%), and G190S in 2 (2.6%) tests. 2010 International journal of molecular medicine Abstract HIV G190A;G190S;K103N 127;151;106 132;156;111 NNRTI;RT 94;79 99;81 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. RESULTS: HIV-1 lacking SL1 (NLDeltaSL1) did not replicate in PM-1 cells until two independent non-synonymous mutations emerged: G913A in the matrix domain (E42K) on day 18 postinfection and C1907T in the SP1 domain (P10L) on day 11 postinfection. 2010 Retrovirology Abstract HIV C1907T;E42K;G913A;P10L 190;156;128;216 196;160;133;220 Matrix;SP1 141;204 147;207 20826651 Human immunodeficiency virus type 1 protease inhibitor drug-resistant mutants give discordant results when compared in single-cycle and multiple-cycle fitness assays. Five protease mutants showed statistically different fitness values by the MCA versus the SCA: the D30N, G48V, I50V, I54L, and I54M mutants. 2010 Journal of clinical microbiology Abstract HIV D30N;G48V;I50V;I54L;I54M 99;105;111;117;127 103;109;115;121;131 PR 5 13 20826651 Human immunodeficiency virus type 1 protease inhibitor drug-resistant mutants give discordant results when compared in single-cycle and multiple-cycle fitness assays. When all the mutants were ranked in order from most to least fit for both assays, 4 protease mutants moved more than 5 positions in rank: the D30N, I54L, I54M, and V82A mutants. 2010 Journal of clinical microbiology Abstract HIV D30N;I54L;I54M;V82A 142;148;154;164 146;152;158;168 PR 84 92 20827161 In-vitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitor S/GSK1349572. We found a seven-, 13- and 18-fold increase in EC50 values to S/GSK1349572 for the HIV-2 double (T97A + Y143C; G140S + Q148R) and triple (G140T + Q148R + N155H) mutants, respectively, obtained from two raltegravir-experienced patients. 2010 AIDS (London, England) Abstract HIV G140S;G140T;N155H;Q148R;Q148R;T97A;Y143C 111;138;154;119;146;97;104 116;144;159;124;151;102;109 20835505 Genetic diversity of human immunodeficiency virus-1 isolates in Parana, Brazil. The most frequent RT mutations in all subtypes were M184V and mutations at codons 215, 41, 103, 67, 219, and 190. 2010 The Brazilian journal of infectious diseases Abstract HIV M184V 52 57 RT 18 20 20836706 Naturally occurring polymorphisms and primary drug resistance profile among antiretroviral-naive individuals in Bangalore, India. Mutations included E138A (etravirine resistance associated) and L210LS (thymidine analog mutation). 2010 AIDS research and human retroviruses Abstract HIV E138A;L210L;L210S 19;64;64 24;70;70 20836706 Naturally occurring polymorphisms and primary drug resistance profile among antiretroviral-naive individuals in Bangalore, India. Novel mutations were observed at positions Q23P/H and A129AG among isolates from our clinical cohort. 2010 AIDS research and human retroviruses Abstract HIV A129A;A129G;Q23H;Q23P 54;54;43;43 60;60;49;49 20849300 Characterization of integrase region polymorphisms in HIV type 1 CRF06_cpx viruses in treatment-naive patients in Estonia. No primary drug resistance mutations against integrase inhibitors were found, but resistance-associated polymorphisms such as V72I, L74I, V201I, and T206S were seen in more than 90% of viruses. 2010 AIDS research and human retroviruses Abstract HIV L74I;T206S;V201I;V72I 132;149;138;126 136;154;143;130 IN 45 54 20849300 Characterization of integrase region polymorphisms in HIV type 1 CRF06_cpx viruses in treatment-naive patients in Estonia. Substitutions E157Q and E157K, associated with raltegravir resistance, were found in only two CRF06_cpx strains. 2010 AIDS research and human retroviruses Abstract HIV E157K;E157Q 24;14 29;19 20849301 Analysis of selection pressure and mutational pattern of HIV type 1 reverse transcriptase region among treated and nontreated patients. Among the mutations positively selected, the frequency of D121Y, I135R, and Q207E increased and the frequency of mutation S48T decreased significantly during treatment failure. 2010 AIDS research and human retroviruses Abstract HIV D121Y;I135R;Q207E;S48T 58;65;76;122 63;70;81;126 20852269 Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. In enzymatic assays, the K103N mutation was associated with moderate reductions in the efficiency of 3' DNA end-directed RNA template cleavage, while comparable efficiency to WT enzyme was observed with regard to minus-strand strong stop DNA synthesis and polymerase processivity. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K103N 25 30 Pol 256 266 20852269 Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. K103N and M230L conferred high-level resistance to both efavirenz (FC=39 and 15.3, respectively) and nevirapine (FC=43.5 and 33), confirming that M230L confers cross-resistance to both drugs while K103N-containing viruses remain susceptible to etravirine. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M230L;M230L;K103N 197;10;146;0 202;15;151;5 20852269 Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. K103N-containing viruses replicated well in the presence of efavirenz and nevirapine, while virus containing M230L displayed substantial replication in the presence of all NNRTIs tested. 2010 The Journal of antimicrobial chemotherapy Abstract HIV M230L;K103N 109;0 114;5 NNRTI 172 178 20852269 Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. METHODS: We compared the effects of K103N, the most prevalent NNRTI resistance mutation, and M230L on enzyme function, virus replication and extent of biochemical inhibition by etravirine, efavirenz and nevirapine. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M230L 36;93 41;98 NNRTI 62 67 20852269 Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. RESULTS: Growth kinetics analyses in cord blood mononuclear cells (CBMCs) demonstrated that K103N-containing virus replicated as well as wild-type (WT) virus and that the M230L-containing virus was severely impaired in replication ability in the absence of NNRTIs. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M230L 92;171 97;176 NNRTI 257 263 20852269 Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. RNA-dependent DNA polymerase assays using a heterogeneous HIV-1 RNA template and purified recombinant WT or mutated reverse transcriptase enzymes revealed that the fold change (FC) for etravirine was 0.7 for K103N and 8 for M230L. 2010 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M230L 208;224 213;229 RT;Pol 116;18 137;28 20852643 Structural basis of HIV-1 resistance to AZT by excision. We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP- and primer-binding sites; and AZTr apo reverse transcriptase. 2010 Nature structural & molecular biology Abstract HIV D67N;K219Q;K70R;M41L;T215Y 138;154;143;133;148 142;159;147;137;153 RT;RT;RT;RT;RT 49;262;92;161;185 70;283;94;163;187 20854144 Characterization of genotypic and phenotypic changes in HIV-1-infected patients with virologic failure on an etravirine-containing regimen in the DUET-1 and DUET-2 clinical studies. The most frequently emerging RT mutations were V179F, V179I, and Y181C, with positions K101 and E138 also showing frequent changes. 2010 AIDS research and human retroviruses Abstract HIV V179F;V179I;Y181C 47;54;65 52;59;70 RT 29 31 20854169 Genotypic impact of prolonged detectable HIV type 1 RNA viral load after HAART failure in a CRF01_AE-infected cohort. NNRTI mutations, M184I/V mutation, thymidine analogue mutations, and K65R were observed in 78.9%, 69%, 20%, and 12.7% of patients, respectively. 2011 AIDS research and human retroviruses Abstract HIV K65R;M184I;M184V 69;17;17 73;24;24 NNRTI 0 5 20860534 HIV-1 drug resistance transmission networks in southwest Switzerland. Resistant mutations to PIs consisted of L10V and accessory mutations 16E and 60E present in all F1 clades. 2010 AIDS research and human retroviruses Abstract HIV L10V 40 44 PI 23 26 20876531 The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. In conclusion, connection subdomain mutation N348I decreases catalytic efficiency and causes in vitro resistance to NVP by decreasing inhibitor binding. 2010 The Journal of biological chemistry Abstract HIV N348I 45 50 20876531 The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. Mutation in p66 alone (p66(N348I)/p51(WT)) caused NVP resistance without significantly affecting RNase H activity, whereas mutation in p51 caused NVP resistance and impaired RNase H, demonstrating that NVP resistance may occur independently from defects in RNase H function. 2010 The Journal of biological chemistry Abstract HIV N348I 27 32 20876531 The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. Surprisingly, mutation in either subunit decreased catalytic rates (k(pol)) of p66(N348I)/p51(N348I), p66(N348I)/p51(WT), and p66(WT)/p51(N348I) without significantly affecting affinity for deoxynucleotide substrate (K(d)(-dNTP)). 2010 The Journal of biological chemistry Abstract HIV N348I;N348I;N348I 83;106;138 88;111;143 Pol 70 73 20876531 The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase (RT) confers clinically significant resistance to both nucleoside and non-nucleoside RT inhibitors (NNRTIs) by mechanisms that are not well understood. 2010 The Journal of biological chemistry Abstract HIV N348I 4 9 RT;NNRTI;RT;RT 56;178;79;163 77;184;81;165 20876531 The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. We characterized RTs mutated in either p66 (p66(N348I)/p51(WT)), p51 (p66(WT)/p51(N348I)), or both subunits (p66(N348I)/p51(N348I)). 2010 The Journal of biological chemistry Abstract HIV N348I;N348I;N348I 48;82;113 53;87;118 RT 17 20 20876531 The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. We used transient kinetics to characterize the enzymatic properties of N348I RT and determine the biochemical mechanism of resistance to the NNRTI nevirapine (NVP). 2010 The Journal of biological chemistry Abstract HIV N348I 71 76 NNRTI;RT 141;77 146;79 20883724 Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure. Double 148R+N155H mutants were also detected in 1.7% of viruses at virological failure in association with E138K and/or G163R. 2010 Antiviral research Abstract HIV E138K;G163R;N155H 107;120;12 112;125;17 20883724 Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure. Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters. 2010 Antiviral research Abstract HIV N155H;N155H;Q148R;Q148R 159;265;149;255 164;270;154;260 20886905 Myristate exposure in the human immunodeficiency virus type 1 matrix protein is modulated by pH. In vivo intracellular localization data revealed that the H89G mutation retargets Gag to intracellular compartments and severely inhibits virus production. 2010 Biochemistry Abstract HIV H89G 58 62 Gag 82 85 20919475 [Prevalence of primary antiretroviral resistance among HIV infected patients in Chile]. Of these, the most common were L63P/T (38 patients), L10I/V (27 patients) and V77I (26 patients). 2010 Revista medica de Chile Abstract HIV L10I;L10V;L63P;L63T;V77I 53;53;31;31;78 59;59;37;37;82 20919475 [Prevalence of primary antiretroviral resistance among HIV infected patients in Chile]. Point mutations for non nucleoside reverse transcriptase inhibitors (NNRTI) were detected in 4.1% of cases (K103N in 1 patient, V179D in 2 patients), for nucleoside reverse transcriptase inhibitors (NRTI) in 8.1% of cases (T215S in 1 patient, V118I in 4 patients, M41L in 1 patient) and for protease inhibitors (PI) in 1.3% of cases. 2010 Revista medica de Chile Abstract HIV K103N;M41L;T215S;V118I;V179D 108;264;223;243;128 114;268;229;248;133 NRTI;NRTI;PR;NNRTI;NRTI;PI 24;154;291;69;199;312 56;186;299;74;203;314 20922443 3,4,5-Trisubstituted-1,2,4-4H-triazoles as WT and Y188L mutant HIV-1 non-nucleoside reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses. The results allowed us to obtain useful information for the design of new compounds with improved potency towards WT HIV-1 or that are potentially active against the Y188L mutant. 2011 Journal of molecular modeling Abstract HIV Y188L 166 171 20922443 3,4,5-Trisubstituted-1,2,4-4H-triazoles as WT and Y188L mutant HIV-1 non-nucleoside reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses. Two 3D-QSAR CoMFA and CoMSIA models were derived, using the TT pEC50 values measured against wild-type (WT) HIV-1 (model A) and the Y188L mutant form (model B), respectively, as the dependent variable. 2011 Journal of molecular modeling Abstract HIV Y188L 132 137 20922443 3,4,5-Trisubstituted-1,2,4-4H-triazoles as WT and Y188L mutant HIV-1 non-nucleoside reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses. Two series of triazoles have been studied, one of which was also screened against the Y188L mutant. 2011 Journal of molecular modeling Abstract HIV Y188L 86 91 20929395 Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing. Among the eight tenofovir-treated subjects, three showed high-frequency (>20%) RT K65R at the time of failure, whereas one showed low-frequency (<20%) L74V; no low-frequency K65R was detected in these subjects. 2011 AIDS research and human retroviruses Abstract HIV L74V;K65R;K65R 151;82;174 155;86;178 RT 79 81 20929395 Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing. Among the nine abacavir-treated subjects, three showed low-frequency K65R; no L74V was detected in these patients. 2011 AIDS research and human retroviruses Abstract HIV K65R;L74V 69;78 73;82 20929395 Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing. At failure, other RT mutations were detected, including low-frequency NNRTI-resistant species detected at >=1 time point in nine subjects; the key NNRTI mutation K103N, however, was always observed at >20% frequency. 2011 AIDS research and human retroviruses Abstract HIV K103N 162 167 NNRTI;NNRTI;RT 70;147;18 75;152;20 20929395 Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing. No K65R or L74V was detected in the samples from the control subject. 2011 AIDS research and human retroviruses Abstract HIV K65R;L74V 3;11 7;15 20929395 Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing. UDPS of the HIV-1 reverse transcriptase (RT) (amino acids 56-120) was performed to detect the key mutations K65R and L74V associated with tenofovir and abacavir use. 2011 AIDS research and human retroviruses Abstract HIV K65R;L74V 108;117 112;121 RT;RT 18;41 39;43 20937812 Resistance profiles of novel electrostatically constrained HIV-1 fusion inhibitors. However, the efficacy of T-20 is attenuated by resistance mutations in gp41, including V38A and N43D. 2010 The Journal of biological chemistry Abstract HIV N43D;V38A 96;87 100;91 gp41 71 75 20943965 Identification of specific determinants of human APOBEC3F, APOBEC3C, and APOBEC3DE and African green monkey APOBEC3F that interact with HIV-1 Vif. Mutants in which E289 is mutated significantly increase hA3F's ability to inhibit viral infectivity in the presence of Vif, and coimmunoprecipitation assays show that binding of Vif to the E289K mutant is decreased. 2010 Journal of virology Abstract HIV E289K 189 194 Vif;Vif 119;178 122;181 20946407 Genetic variation of the HIV-1 integrase region in newly diagnosed anti-retroviral drug-naive patients with HIV/AIDS in Korea. Major mutation sites in the integrase (E92Q, F121Y, G140A/S, Y143C/R, Q148H/R/K and N155H) were not detected, and only a few minor mutation sites (L74M, V151I, E157Q, V165I, I203M, S230N and D232N) were identified in 21 strains (28%). 2011 Clinical microbiology and infection Abstract HIV D232N;E157Q;E92Q;F121Y;G140A;G140S;I203M;L74M;N155H;Q148H;Q148K;Q148R;S230N;V151I;V165I;Y143C;Y143R 191;160;39;45;52;52;174;147;84;70;70;70;181;153;167;61;61 196;165;43;50;59;59;179;151;89;79;79;79;186;158;172;68;68 IN 28 37 20950146 Sequence analysis of the gag-pol gene of human immunodeficiency virus type 1 of intersubtype (B'/C) recombinant strain in Beijing, China. We identified I7V, E91G, N242T, and K361R in the gag gene and R290I (HXB2 positions) in the pol gene as signature amino acid substitutions characteristic of HIV-1 CRF07_BC from the Beijing lineage. 2011 AIDS research and human retroviruses Abstract HIV E91G;I7V;K361R;N242T;R290I 19;14;36;25;62 23;17;41;30;67 Pol;Gag 92;49 95;52 20954462 Genotypic evaluation of etravirine sensitivity of clinical human immunodeficiency virus type 1 (HIV-1) isolates carrying resistance mutations to nevirapine and efavirenz. The V1061 and V179D mutations were more frequent in the ARV-naive group than in the NNRTI-experienced one. 2010 Acta clinica Belgica Abstract HIV V179D 14 19 NNRTI 84 89 20954831 Short communication: Transmitted drug resistance and molecular epidemiology in antiretroviral naive HIV type 1-infected patients in Rhode Island. Drug resistance mutations were identified in 7/35 [20%; 95% confidence interval (CI), 0.08-0.37] patients, six of whom had K103N. 2011 AIDS research and human retroviruses Abstract HIV K103N 123 128 20954831 Short communication: Transmitted drug resistance and molecular epidemiology in antiretroviral naive HIV type 1-infected patients in Rhode Island. Individuals in one cluster all had K103N and were MSM who had attended local bathhouses. 2011 AIDS research and human retroviruses Abstract HIV K103N 35 40 20954909 High HIV type 1 group M pol diversity and low rate of antiretroviral resistance mutations among the uniformed services in Kinshasa, Democratic Republic of the Congo. Only one strain harbored a single mutation, I54V, associated with drug resistance to protease inhibitors. 2011 AIDS research and human retroviruses Abstract HIV I54V 44 48 PR 85 93 20956600 Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates. Although samples with the Y143R/C mutation had reduced susceptibility to RAL, they remained susceptible to MK-2048 and compound G. 2011 Antimicrobial agents and chemotherapy Abstract HIV Y143C;Y143R 26;26 33;33 20956600 Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates. Samples with Q148H/R mutations had elevated fold change values with all compounds tested. 2011 Antimicrobial agents and chemotherapy Abstract HIV Q148H;Q148R 13;13 20;20 20956600 Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates. Samples with the N155H mutation had no reduced susceptibility to compound G. 2011 Antimicrobial agents and chemotherapy Abstract HIV N155H 17 22 20960178 Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. 2010 Virologica Sinica Abstract HIV G73S;L90M;M46I 31;36;26 35;40;30 20960178 Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. 2010 Virologica Sinica Abstract HIV G73S 137 141 20960178 Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 2010 Virologica Sinica Abstract HIV G73S;L90M;M46I;G73S;L90M;M46I 93;98;88;26;54;49 97;102;92;30;58;53 20960178 Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M. 2010 Virologica Sinica Abstract HIV G73S;L90M;M46I 72;122;117 76;126;121 20961278 HIV-1 integrase sequence variability in antiretroviral naive patients and in triple-class experienced patients subsequently treated with raltegravir. Four ARV-naive (5.3%) and two ARV-treated patients (2.7%) had one of the following minor INI-resistance mutations: L74M, E157Q, G163R, and R263K but there was no association between baseline raltegravir genotype and subsequent response to raltegravir treatment. 2010 AIDS research and human retroviruses Abstract HIV E157Q;G163R;L74M;R263K 121;128;115;139 126;133;119;144 IN 89 92 20964479 Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy. Among NNRTI mutations, subtype G patients had an increased risk for A98G (AOR = 2.40, p = 0.036) and V106I (AOR = 6.15, p = 0.010), whereas subtype CRF02_AG patients had an increased risk for V90I (AOR = 3.16; p = 0.003) and a decreased risk for A98G (AOR = 0.48, p = 0.019). 2011 AIDS research and human retroviruses Abstract HIV A98G;A98G;V106I;V90I 68;246;101;192 72;250;106;196 NNRTI 6 11 20964479 Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy. Multivariate analysis showed that CRF02_AG was less likely to have the M41L mutation compared to other subtypes [adjusted odds ratio (AOR) = 0.35; p = 0.022]. 2011 AIDS research and human retroviruses Abstract HIV M41L 71 75 20964479 Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy. Subtype A patients showed a 42.5-fold increased risk (AOR = 42.5, p = 0.001) for the L210W mutation. 2011 AIDS research and human retroviruses Abstract HIV L210W 85 90 20964479 Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy. The most common NNRTI mutations were Y181C (49.7%), K103N (36.4%), G190A (26.3%), and A98G (19.5%). 2011 AIDS research and human retroviruses Abstract HIV A98G;G190A;K103N;Y181C 86;67;52;37 90;72;57;42 NNRTI 16 21 20964479 Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy. The most common NRTI mutations were M184V (89.1%) and thymidine analog mutations (TAMs). 2011 AIDS research and human retroviruses Abstract HIV M184V 36 41 NRTI 16 20 20964489 Emerging transmitted drug resistance in treatment-naive human immunodeficiency virus-1 CRF06_cpx-infected patients in Estonia. A total of 2.8% of sequences harboured mutations indicating nucleoside/nucleotide reverse transcriptase inhibitor resistance (M41L, M184V, M184I, T215C and T215D), 2.1% non-nucleoside reverse transcriptase inhibitor resistance (K103N, P225H) and 2.8% protease inhibitor resistance (M46I, L90M). 2011 Scandinavian journal of infectious diseases Abstract HIV K103N;L90M;M184I;M184V;M41L;M46I;P225H;T215C;T215D 228;288;139;132;126;282;235;146;156 233;292;144;137;130;286;240;151;161 NNRTI;RT;PR 169;82;251 205;103;259 20981787 Low prevalence of transmitted drug resistance among newly diagnosed HIV-1 patients in Latvia. All four patients displayed single, but different resistance mutations (M46I, F53L, M41L, and G190A). 2010 Journal of medical virology Abstract HIV F53L;G190A;M41L;M46I 78;94;84;72 82;99;88;76 21030679 Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Furthermore, our structures predict physical proximity and an interaction between HIV-1 IN mutant residues His148 and Ser/Ala140, rationalizing the coevolution of Q148H and G140S/A mutations in drug-resistant viral strains. 2010 Proc Natl Acad Sci U S A Abstract HIV G140A;G140S;Q148H 173;173;163 180;180;168 IN 88 90 21030679 Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. We show that like the Q148H/G140S and N155H HIV-1 IN variants, the analogous S217H and N224H PFV INs display reduced sensitivity to raltegravir in vitro. 2010 Proc Natl Acad Sci U S A Abstract HIV G140S;N155H;N224H;Q148H;S217H 28;38;87;22;77 33;43;92;27;82 IN;IN 50;97 52;100 21041913 HIV type-1 drug resistance in antiretroviral treatment-naive adults infected with non-B subtype virus in the United Kingdom. M184V was more common in non-B subtypes (non-B 30% versus B 5%; P<0.001) and T215 variants were more common in subtype B (non-B 10% versus B 49%; P<0.001). 2010 Antiviral therapy Abstract HIV M184V 0 5 21054750 Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. CONCLUSIONS: Over the 21-day treatment period, ATC showed promising antiviral activity and was well tolerated in treatment-experienced patients with M184V, with or without additional TAMs. 2011 HIV medicine Abstract HIV M184V 149 154 21054750 Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. Few genotypic changes were detected at day 21 [two patients (600 mg ATC) lost and three patients (800 mg ATC) gained a TAM] and all patients with detectable virus retained the M184V mutation. 2011 HIV medicine Abstract HIV M184V 176 181 21054750 Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. METHODS: In this Phase II randomized, double-blind study, 51 treatment-experienced HIV-1-infected patients with the reverse transcriptase mutation M184V who were failing therapy which included lamivudine (3TC) were randomized to receive twice-daily 600 mg ATC, 800 mg ATC or 150 mg 3TC for 21 days. 2011 HIV medicine Abstract HIV M184V 147 152 RT 116 137 HIV infections 83 97 21056001 Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients. Four patients with the M184V mutation also harbored the K65R or the K103N mutation. 2011 Journal of clinical virology Abstract HIV K103N;K65R;M184V 68;56;23 73;60;28 21056001 Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients. K65R, K103N, and M184V variants at low frequencies were detected by allele-specific real-time PCR. 2011 Journal of clinical virology Abstract HIV K103N;M184V;K65R 6;17;0 11;22;4 21056001 Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients. RESULTS: Minority drug-resistant HIV-1 variants were detected in 20/146 patients (13.7%): the M184V mutation in 12/146 patients (8.2%), the K103N mutation in 8/146 patients (5.5%), and the K65R mutation in 4/146 patients (2.7%). 2011 Journal of clinical virology Abstract HIV K103N;K65R;M184V 140;189;94 145;193;99 21056575 Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. Increases in the population of pretranslocated complexes were accompanied by increases in PFA activity, while F61A is literally resistant to PFA. 2011 Journal of molecular biology Abstract HIV F61A 110 114 21056575 Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. We demonstrate that F61A causes a strong bias to the posttranslocational state, while A62V shows a subtle bias toward pretranslocation regardless of the mutational background. 2011 Journal of molecular biology Abstract HIV A62V;F61A 86;20 90;24 21056575 Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. We employed site-specific footprinting, binding assays, and DNA-synthesis inhibition experiments to study F61A and A62V, alone and against a background of known drug-resistance mutations. 2011 Journal of molecular biology Abstract HIV A62V;F61A 115;106 119;110 21056575 Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. We focused on substitution F61A and the neighboring A62V that is frequently associated with drug-resistance-conferring mutations. 2011 Journal of molecular biology Abstract HIV A62V;F61A 52;27 56;31 21056575 Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. We propose that a binary, pretranslocated complex in a closed conformation is stabilized with A62V and destabilized with F61A. 2011 Journal of molecular biology Abstract HIV A62V;F61A 94;121 98;125 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. In addition the double R77A and R80A mutation known to inactivate the mitochondriotoxic Vpr(71-82) domain, has no effect on the biological properties of the Vpr(77-92) domain. 2010 PloS one Abstract HIV R77A;R80A 23;32 27;36 Vpr;Vpr 88;157 91;160 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. We also found that the I84P mutation or the IIQ/VTR(83-85) and T89A substitutions in the Vpr(77-92) sequence prevent PP2A(1) binding, cell penetration and apoptosis. 2010 PloS one Abstract HIV I84P;T89A 23;63 27;67 Vpr 89 92 21078948 In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043. Population sequencing and sequence determination of cloned envelope genes uncovered five gp120 mutations at four loci (V68A, L116I, S375I/N, and M426L) associated with BMS-488043 resistance. 2011 Antimicrobial agents and chemotherapy Abstract HIV L116I;M426L;S375I;S375N;V68A 125;145;132;132;119 130;150;139;139;123 Env;gp120 59;89 67;94 21084518 In vitro selection of clinically relevant bevirimat resistance mutations revealed by "deep" sequencing of serially passaged, quasispecies-containing recombinant HIV-1. For the two groups with V370A levels below consistent detectability by deep sequencing, the initial selection of V370A required 3 to 4 weeks of exposure to a narrow range of bevirimat concentrations, whereas for the group with the V370A minority, selection occurred immediately. 2011 Journal of clinical microbiology Abstract HIV V370A;V370A;V370A 24;113;231 29;118;236 21084518 In vitro selection of clinically relevant bevirimat resistance mutations revealed by "deep" sequencing of serially passaged, quasispecies-containing recombinant HIV-1. Unscreened mutations were present in all groups, and a V370A minority not originally detected by bulk sequencing was present in one group. 2011 Journal of clinical microbiology Abstract HIV V370A 55 60 21084518 In vitro selection of clinically relevant bevirimat resistance mutations revealed by "deep" sequencing of serially passaged, quasispecies-containing recombinant HIV-1. V370A, occurring together with another preexisting, unscreened resistance mutation, was selected in all groups in the presence of a bevirimat concentration above 0.1 muM. 2011 Journal of clinical microbiology Abstract HIV V370A 0 5 21087198 Presence of drug resistance mutations among drug-naive patients in Morocco. The presence of DRMs was found in four (5.06%) of 91 patients; resistance mutations to NRTIs were M184V and T215I/S revertant mutations; resistance to NNRTIs was associated with K103N and resistance to PIs with V82A. 2011 AIDS research and human retroviruses Abstract HIV K103N;M184V;T215I;T215S;V82A 178;98;108;108;211 183;103;115;115;215 NNRTI;NRTI;PI 151;87;202 157;92;205 21091377 Transmitted HIV type 1 drug resistance among individuals with recent HIV infection in East and Southern Africa. Among four partners with sequence data available, transmission linkage was confirmed and two had the same TDRMs as the newly infected volunteer (both K103N). 2011 AIDS research and human retroviruses Abstract HIV K103N 150 155 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. CONCLUSION: Persistence of the K103N mutation as a majority quasispecies may ensue after a very short exposure to efavirenz. 2009 Journal of medical case reports Abstract HIV K103N 31 36 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Here, we report on the rapid and long lasting selection of a K103N bearing strain as the dominant quasispecies after very short exposure to efavirenz in vivo. 2009 Journal of medical case reports Abstract HIV K103N 61 66 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. INTRODUCTION: Selection of the K103N mutation is associated with moderately reduced in vitro fitness of HIV. 2009 Journal of medical case reports Abstract HIV K103N 31 36 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Our case would therefore suggest that the presence of the K103N mutation should always be ruled out by genotyping resistance testing assays, even after minimal exposures to efavirenz. 2009 Journal of medical case reports Abstract HIV K103N 58 63 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Strains bearing K103N in vivo tend to persist, even in the absence of additional drug pressure, as minority quasispecies, often undetectable in genotyping resistance testing assays, performed at standard conditions. 2009 Journal of medical case reports Abstract HIV K103N 16 21 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. The genotyping resistance testing assay was performed both on HIV RNA and HIV DNA from plasma, yielding an identical pattern with the isolate presence of the K103N mutation in the prevalent strain. 2009 Journal of medical case reports Abstract HIV K103N 158 163 21093412 Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T lymphocytes influence viral entry co-receptor expression and susceptibility to superinfection. Moreover, the cells expressing the Arg75Thr variant Nef significantly impaired protection from superinfection by CCR5-tropic, but not CXCR4-tropic, viruses. 2010 Biochemical and biophysical research communications Abstract HIV R75T 35 43 Nef 52 55 21093412 Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T lymphocytes influence viral entry co-receptor expression and susceptibility to superinfection. The analysis of autologous nef sequences isolated from a cohort of total 235 subjects in Japan revealed that the subjects showing amino acid variations, such as Arg75Thr and Tyr85Phe, located within the proline-rich region were significantly over-represented by those having HLA-B*3501. 2010 Biochemical and biophysical research communications Abstract HIV R75T;Y85F 161;174 169;182 Nef 27 30 21093412 Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T lymphocytes influence viral entry co-receptor expression and susceptibility to superinfection. The Arg75Thr variant Nef selectively impaired CCR5, but not CXCR4, down-regulation activity from the cell surface; whereas the Tyr85Phe variant Nef affected neither CCR5 nor CXCR4 down-regulation activity. 2010 Biochemical and biophysical research communications Abstract HIV R75T;Y85F 4;127 12;135 Nef;Nef 21;144 24;147 21094281 Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study. Also, new amino acid substitutions of as yet unknown significance were identified: E152K/H, S153F/L, N155I and E157G. 2011 Infection, genetics and evolution Abstract HIV E152H;E152K;E157G;N155I;S153F;S153L 83;83;111;101;92;92 90;90;116;106;99;99 21094281 Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study. None of the known integrase resistance mutations were observed, except E157Q found in one Cambodian subject (1.1%, CI 95% 0.02-6.3%). 2011 Infection, genetics and evolution Abstract HIV E157Q 71 76 IN 18 27 21096145 A signal processing-based bioinformatics approach to assessing drug resistance: human immunodeficiency virus as a case study. For example, G36S and V38M mutation in the Human Immunodeficiency Virus (HIV) Transmembrane glycoprotein (gp41) has been found to cause 100-fold resistance. 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Abstract HIV G36S;V38M 13;22 17;26 gp41 106 110 21098485 In vitro selection and characterization of HIV-1 variants with increased resistance to sifuvirtide, a novel HIV-1 fusion inhibitor. A downstream substitution at position 126 (N126K) in the C-terminal heptad repeat region was also found. 2011 The Journal of biological chemistry Abstract HIV N126K 43 48 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. M184V and nonnucleoside reverse transcriptase inhibitor-associated mutations emerged within 6 months of EVF; thymidine-analog-mutations arose after 12 months. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 0 5 NNRTI 10 45 21106747 Dynamics of in vitro fitness recovery of HIV-1. One common change, V35I, in the nuclear localization signal of the p17 protein appeared in four viruses of three different lineages. 2011 Journal of virology Abstract HIV V35I 19 23 21106747 Dynamics of in vitro fitness recovery of HIV-1. Other common alterations mapped in position E196K of the reverse transcriptase or in position S316K of the V3 loop of the gp120 residue that is associated with the X4/R5 phenotype. 2011 Journal of virology Abstract HIV E196K;S316K 44;94 49;99 RT;gp120 57;122 78;127 21107269 Influence of major HIV-1 protease inhibitor resistance mutations on CTL recognition. CONCLUSIONS: PI mutations, G48V, M46I, and I47A, can abrogate CTL recognition, indicating potential interactions between development of drug resistance and CTL response. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48V;I47A;M46I 27;43;33 31;47;37 PI 13 15 21107269 Influence of major HIV-1 protease inhibitor resistance mutations on CTL recognition. Furthermore, M46I, I47A, and I50V could impair or abolish CTL recognition in many patients. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I47A;I50V;M46I 19;29;13 23;33;17 21107269 Influence of major HIV-1 protease inhibitor resistance mutations on CTL recognition. In contrast, M46L and I47V showed good CTL recognition in nearly all patients. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I47V;M46L 22;13 26;17 21107269 Influence of major HIV-1 protease inhibitor resistance mutations on CTL recognition. Recently, we identified KMIGGIGGF (KF9) as a HLA-B*1501-restricted CTL epitope, including several major PI resistance mutations (M46I/L, I47A/V, G48V, I50V). 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48V;I47A;I47V;I50V;M46I;M46L 145;137;137;151;129;129 149;143;143;155;135;135 PI 104 106 21107269 Influence of major HIV-1 protease inhibitor resistance mutations on CTL recognition. RESULTS: G48V abolished KF9 recognition by CTL in all patients. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G48V 9 13 21109032 Increased expression and immunogenicity of HIV-1 protease following inactivation of the enzymatic activity. Mutations resulting in enzymatic inactivation (D25N) and resistance to standard antiretroviral drugs (V82F/I84V) were introduced in order to examine the impact of the enzymatic activity on immunogenicity and the possibility to induce immune responses against drug resistant protease, respectively. 2011 Vaccine Abstract HIV V82F;D25N;I84V 102;47;107 106;51;111 PR 274 282 21114465 Drug resistance and HCV coinfection in former blood donors infected with HIV type 1 in China. Drug-resistant mutations to reverse transcriptase inhibitors were detected in one-third of treatment failure patients, with K103N as the most frequent mutation. 2011 AIDS research and human retroviruses Abstract HIV K103N 124 129 RT 28 49 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. No other known INI RAM was detected.Under RAL selective pressure in vitro, a ROD variant carrying the Q91R+I175M mutations was selected. 2010 Retrovirology Abstract HIV I175M;Q91R 107;102 112;106 IN 15 18 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The N155 H INI resistance-associated mutation (RAM) was detected in the virus population from one ARV-treated, INI-naive patient, and the 72I and 201I polymorphisms were detected in samples from 36 and 38 patients respectively. 2010 Retrovirology Abstract HIV N155H 4 10 IN;IN 11;111 14;114 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The Q91R and I175M mutations emerged simultaneously and conferred phenotypic resistance (13-fold increase in IC50). 2010 Retrovirology Abstract HIV I175M;Q91R 13;4 18;8 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The Q91R+I175M combination was absent from all clinical isolates. 2010 Retrovirology Abstract HIV I175M;Q91R 9;4 14;8 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Two new mutations (Q91R and I175M) that conferred high resistance to RAL were selected in vitro, which might affect therapeutic outcome. 2010 Retrovirology Abstract HIV I175M;Q91R 28;19 33;24 21115794 In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. S/GSK1349572 demonstrated activity against site-directed molecular clones containing the raltegravir-resistant signature mutations Y143R, Q148K, N155H, and G140S/Q148H (FCs, 1.4, 1.1, 1.2, and 2.6, respectively), while these mutants led to a high FC in the EC(50) of raltegravir (11- to >130-fold). 2011 Antimicrobial agents and chemotherapy Abstract HIV G140S;N155H;Q148H;Q148K;Y143R 156;145;162;138;131 161;150;167;143;136 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. In such patients, two protease mutations, I54V and V82A, occur more frequently. 2010 PLoS pathogens Abstract HIV I54V;V82A 42;51 46;55 PR 22 30 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Primary CD4 T cells expressing I54V or V82A protease underwent less cell death than with WT or other mutant proteases. 2010 PLoS pathogens Abstract HIV I54V;V82A 31;39 35;43 PR;PR 44;108 52;117 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Focusing on resistant viruses carrying the V38A mutation in gp41, we found ENF-resistant virus to be 17+-3% less fit than ENF-sensitive virus in the absence of the drug, and that the loss of resistant virus during therapy interruption was primarily due to this fitness cost. 2010 PLoS computational biology Abstract HIV V38A 43 47 gp41 60 64 21130027 Minority HIV mutation detection in dried blood spots indicates high specimen integrity and reveals hidden archived drug resistance. STUDY DESIGN: Evaluate nucleic acids from the DBS of 33 antiretroviral-experienced subtype B-infected subjects for minority M41L, K65R, K70R, K103N, Y181C, M184V, and T215Y/F mutations by real-time PCR. 2011 Journal of clinical virology Abstract HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y;Y181C 142;130;136;156;124;167;167;149 147;134;140;161;128;174;174;154 21133347 Rational approaches for the design of effective human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitors. The binding of several classes of nonnucleoside reverse transcriptase inhibitors (NNRTIs) to wild-type (wtRT) and K103N mutant (mRT) human immunodeficiency virus type 1 (HIV-1) reverse transcriptase is studied by molecular dynamics and energy decomposition techniques. 2011 Journal of chemical information and modeling Abstract HIV K103N 114 119 NNRTI;RT;NNRTI;RT 34;177;82;106 69;198;88;108 21135184 Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes. The results show that ETR selected mutations at positions V90I, K101Q, E138K, V179D/E/F, Y181C, V189I, G190E, H221H/Y, and M230L and that E138K was the first of these to emerge in most instances. 2011 Antimicrobial agents and chemotherapy Abstract HIV E138K;E138K;G190E;H221H;H221Y;K101Q;M230L;V179D;V179E;V179F;V189I;V90I;Y181C 71;138;103;110;110;64;123;78;78;78;96;58;89 76;143;108;117;117;69;128;87;87;87;101;62;94 21135184 Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes. Viral clones containing E138K displayed low-level phenotypic resistance to ETR (3.8-fold) and modestly impaired replication capacity (2-fold) compared to wild-type virus. 2011 Antimicrobial agents and chemotherapy Abstract HIV E138K 24 29 21135184 Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes. We identified K101Q, E138K, V179E, V189I, G190E, and H221Y as mutations not included among the 17 currently recognized resistance-associated mutations for ETR. 2011 Antimicrobial agents and chemotherapy Abstract HIV E138K;G190E;H221Y;K101Q;V179E;V189I 21;42;53;14;28;35 26;47;58;19;33;40 21142105 Synthesis and biological evaluation of aryl-phospho-indole as novel HIV-1 non-nucleoside reverse transcriptase inhibitors. Chemical variation in the phosphorus linker led to the discovery of 3-phenyl-methyl-phosphinate-2-carboxamide 14, which possessed excellent potency against wild-type HIV-1 as well as viruses bearing K103N and Y181C single mutants in the reverse transcriptase gene. 2011 Journal of medicinal chemistry Abstract HIV K103N;Y181C 199;209 204;214 RT 237 258 21142800 Identification of the DC-SIGN-interactive domains on the envelope glycoprotein of HIV-1 CRF07_BC. Capture assays showed that the DC-SIGN-binding capacity of pseudoviruses with N275Q or N351Q decreased significantly. 2011 AIDS research and human retroviruses Abstract HIV N275Q;N351Q 78;87 83;92 21142800 Identification of the DC-SIGN-interactive domains on the envelope glycoprotein of HIV-1 CRF07_BC. Pseudotyped viruses containing single (N233Q, N275Q, N330Q, N351Q, N355Q, N381Q, and N387Q), double (N233Q + N275Q, N233Q + N351Q, N275Q + N351Q), or triple (N233Q + N275Q + N351Q) N-glycan mutant gp120 were generated. 2011 AIDS research and human retroviruses Abstract HIV N233Q;N233Q;N233Q;N233Q;N275Q;N275Q;N275Q;N275Q;N330Q;N351Q;N351Q;N351Q;N351Q;N355Q;N381Q;N387Q 39;101;116;158;46;109;131;166;53;60;124;139;174;67;74;85 44;107;121;164;51;114;136;171;58;65;129;144;179;72;79;90 gp120 197 202 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. A structure prediction of the protease carrying the L10I mutation was determined. 2011 AIDS research and human retroviruses Abstract HIV L10I 52 56 PR 30 38 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. Furthermore, viruses carrying the major mutation D30N or the minor mutation L10I showed a significant decrease in RC (p-value <0.05), whereas viruses carrying the minor mutation L63P had RC similar to wild-type virus. 2011 AIDS research and human retroviruses Abstract HIV D30N;L10I;L63P 49;76;178 53;80;182 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. In addition, the L10I mutation conferred resistance to saquinavir, which was supported by the higher prevalence in the cohort of the L10I mutation among patients with SQV resistance. 2011 AIDS research and human retroviruses Abstract HIV L10I;L10I 17;133 21;137 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. In conclusion, the L10I mutation impairs RC and confers resistance to SQV, similarly to other major mutations, which may be related with changes in the conformation in the protease binding site. 2011 AIDS research and human retroviruses Abstract HIV L10I 19 23 PR 172 180 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. The molecular modeling suggests that L10I may affect the conformation of Leu-23, a critical residue in the substrate binding site. 2011 AIDS research and human retroviruses Abstract HIV L10I 37 41 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. The prevalence of the minor mutation L10I had a pattern similar to that found for major mutations D30N, with a low prevalence (4.9%) in naive patients and significantly higher prevalence in treated patients. 2011 AIDS research and human retroviruses Abstract HIV D30N;L10I 98;37 102;41 21142921 The HIV type 1 protease L10I minor mutation decreases replication capacity and confers resistance to protease inhibitors. We characterized the HIV protease minor mutations, L10I, compared to the minor mutation, L63P, and the major mutation D30N and their impact on viral fitness and resistance to protease inhibitors. 2011 AIDS research and human retroviruses Abstract HIV D30N;L10I;L63P 118;51;89 122;55;93 PR;PR 25;175 33;183 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. No V75I cases were detected (95% confidence interval, 0%-2.2%). 2011 The Journal of infectious diseases Abstract HIV V75I 3 7 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. Recent in vitro studies suggest that acyclovir may directly inhibit HIV-1 replication and can select for a specific HIV-1 reverse transcriptase mutation (V75I) with concomitant loss of an anti-HIV-1 effect. 2011 The Journal of infectious diseases Abstract HIV V75I 154 158 RT 122 143 21149628 Three residues in HIV-1 matrix contribute to protease inhibitor susceptibility and replication capacity. Three amino acid changes in matrix (R76K, Y79F, and T81A) had an impact on replication capacity as well as drug susceptibility. 2011 Antimicrobial agents and chemotherapy Abstract HIV R76K;T81A;Y79F 36;52;42 40;56;46 Matrix 28 34 21157296 Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. CONCLUSION: The presence of K103N mutant virus in plasma above 2000 copies/ml prior to therapy in treatment-naive individuals correlated with increased risk of virologic failure of these efavirenz-containing triple-drug regimens. 2011 AIDS (London, England) Abstract HIV K103N 28 33 21157296 Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. Here, we analyzed whether the presence of low levels of K103N at baseline correlated with virologic failure. 2011 AIDS (London, England) Abstract HIV K103N 56 61 21157296 Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. METHODS: Available baseline plasma samples (n = 485) were amplified and tested for K103N using an allele-specific PCR (AS-PCR) assay with a lower detection cut-off of 0.5%. 2011 AIDS (London, England) Abstract HIV K103N 83 88 21157296 Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. Multivariate logistic regression analysis showed that K103N viral load at least 2000 copies/ml increased the risk of virologic failure with an odds ratio of 47.4 (95% confidence interval 5.2-429.2, P = 0.0006). 2011 AIDS (London, England) Abstract HIV K103N 54 59 21157296 Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. RESULTS: Sixteen of 476 (3.4%) evaluable participants had low-level K103N at baseline by AS-PCR (0.8-15%). 2011 AIDS (London, England) Abstract HIV K103N 68 73 21157296 Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. The abundance of the K103N subpopulation at baseline distinguished individuals with virologic failure from those who responded durably to efavirenz-containing therapy. 2011 AIDS (London, England) Abstract HIV K103N 21 26 21159865 A conserved determinant in the V1 loop of HIV-1 modulates the V3 loop to prime low CD4 use and macrophage infection. Thus, we identified an E153G substitution that conferred high levels of macrophage infectivity for several heterologous R5 envelopes, while the reciprocal G153E substitution abrogated infection. 2011 Journal of virology Abstract HIV E153G;G153E 23;155 28;160 Env 123 132 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. The most deleterious mutations were K65R, Q151M, M184V/I, and T215Y/F, each of them decreasing susceptibility to most of the NRTIs. 2010 PloS one Abstract HIV K65R;M184I;M184V;Q151M;T215F;T215Y 36;49;49;42;62;62 40;56;56;47;69;69 NRTI 125 130 21182081 Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes carrying strong ability to suppress HIV-1 replication. Pol 463-10-specific CTL failed both to kill the V9A virus-infected cells and to suppress replication of the V9A mutant. 2011 European journal of immunology Abstract HIV V9A;V9A 48;108 51;111 Pol 0 3 21182081 Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes carrying strong ability to suppress HIV-1 replication. Sequence analysis of these epitopes showed that a V-to-A substitution at the 9th position (V9A) of Pol 463-10 was significantly associated with the HLA-Cw(*) 1202 allele and that the V9A mutant was slowly selected in the HLA-Cw(*) 1202(+) individuals. 2011 European journal of immunology Abstract HIV V9A;V9A 91;183 94;186 Pol 99 102 21182081 Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes carrying strong ability to suppress HIV-1 replication. These results indicate that the V9A mutation was selected as an escape mutant by the Pol463-10-specific CTL. 2011 European journal of immunology Abstract HIV V9A 32 35 Pol 85 88 21190485 Gender differences in HIV drug resistance mutations and virological outcome. There were no major statistically significant differences in the baseline demographic, clinical, or genotypic characteristics between males and females before GRT except for race, presence of coexisting hepatitis B and C infection, prior diagnosis of tuberculosis, presence of thymidine analogue mutations (TAMs), and protease inhibitor (PI) mutations L90M and I84V (p < 0.05). 2011 Journal of women's health (2002) Abstract HIV I84V;L90M 361;352 365;356 PR;PI 318;338 326;340 Tuberculosis 251 263 21207961 Identification of a novel scaffold for allosteric inhibition of wild type and drug resistant HIV-1 reverse transcriptase by fragment library screening. Ten hits were discovered, and their affinities and resistance profiles were evaluated with wild type and three drug resistant enzyme variants (K103N, Y181C, and L100I). 2011 Journal of medicinal chemistry Abstract HIV K103N;L100I;Y181C 143;161;150 148;166;155 21220490 Cell-penetrating TAT-FOXO3 fusion proteins induce apoptotic cell death in leukemic cells. In this study, wild-type FOXO3 and FOXO3 mutated on Akt sites [FOXO3 T32A/S253A/S315A or TM (triple mutant)] were fused to the TAT-PTD. 2011 Molecular cancer therapeutics Abstract HIV T32A;S253A;S315A 69;74;80 73;79;85 Tat 127 130 21233638 Impact of HIV-1 group O genetic diversity on genotypic resistance interpretation by algorithms designed for HIV-1 group M. RESULTS: All HIV-O samples naturally exhibited the A98G and V179E resistance mutations in the reverse transcriptase region; 54% of samples presented the Y181C mutation, conferring resistance to nonnucleoside reverse transcriptase inhibitors. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A98G;V179E;Y181C 51;60;153 55;65;158 NNRTI;RT 194;94 229;115 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. However, Vpu-A18H was confined to an endoplasmic reticulum (ER)-like distribution, resulting in impaired down-regulation of BST-2 and reduced virion release. 2011 Virology Abstract HIV A18H 13 17 Vpu 9 12 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-I17A, -A18F, -W22L, and -S23L co-localized with BST-2 within endosomal membranes while effectively enhancing virion release and down-regulating surface BST-2. 2011 Virology Abstract HIV A18F;I17A;S23L;W22L 10;4;28;17 15;8;33;22 Vpu 0 3 21241214 Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission. Infants infected before 6 weeks of age who received either SD- or ED-NVP were more likely to have Y181C or K103N; these mutations were also more likely to persist at high frequencies through 1 year of age. 2011 AIDS research and human retroviruses Abstract HIV K103N;Y181C 107;98 112;103 21245516 Update of the drug resistance mutations in HIV-1: December 2010. For etravirine, L100I*, K101P*, and Y181C*/I*/V* are denoted with asterisks (instead of bolded) to reflect that these individual mutations each have the greatest impact (ie, highest weighting scores) on reduced phenotypic susceptibility and impaired clinical response when compared with other etravirine mutations (Haddad M et al, CROI, 2010; Abstract 574). 2010 Topics in HIV medicine Abstract HIV K101P;L100I;Y181C 24;16;36 29;21;48 21245516 Update of the drug resistance mutations in HIV-1: December 2010. In addition, the tipranavir/ritonavir N83D mutation designation was changed to boldface to indicate its recognition as a major mutation rather than a minor mutation. 2010 Topics in HIV medicine Abstract HIV N83D 38 42 21245516 Update of the drug resistance mutations in HIV-1: December 2010. The mutations I13V, K20M/R, E35G, and L90M were removed from the tipranavir/ritonavir bar, reflecting new understanding. 2010 Topics in HIV medicine Abstract HIV E35G;I13V;K20M;K20R;L90M 28;14;20;20;38 32;18;26;26;42 21245516 Update of the drug resistance mutations in HIV-1: December 2010. This update includes 9 new mutations- E138G and E138K for etravirine (Haddad M et al, CROI, 2010; Abstract 574, and Vingerhoets J et al, Antivir Ther, 2010;15 [Suppl 2]:A125); E92Q for raltegravir (Geretti AM et al, Antivir Ther, 2010;15 [Suppl 2]:A62; Cooper et al, N Engl J Med, 2008;359:355-365; and Malet I et al, Antimicrob Agents Chemother, 2008;52:1351-1358); and M36L, M36V, H69R, L89I, L89M, and L89V for tipranavir/ritonavir. 2010 Topics in HIV medicine Abstract HIV E138G;E138K;E92Q;H69R;L89I;L89M;L89V;M36L;M36V 38;48;176;383;389;395;405;371;377 43;53;180;387;393;399;409;375;381 21248851 Atomic-level modelling of the HIV capsid. Two mutant CA proteins with engineered disulphides at different positions (P17C/T19C and N21C/A22C) converged onto the same quaternary structure, indicating that the disulphide-crosslinked proteins recapitulate the structure of the native pentamer. 2011 Nature Abstract HIV P17C;A22C;N21C;T19C 75;94;89;80 79;98;93;84 Capsid 11 13 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Analysis of the genotypic and phenotypic testing over the course of this patient's therapy lead us to hypothesize that TFV-DF resistance emerged upon appearance of the previously unreported K70Q mutation in the Q151Mc background. 2011 PloS one Abstract HIV K70Q 190 194 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Biochemical experiments established that the increased resistance to tenofovir is not the result of enhanced excision, as K70Q/Q151Mc RT exhibited diminished, rather than enhanced ATP-based primer unblocking activity. 2011 PloS one Abstract HIV K70Q;Q151M 122;127 126;132 RT 134 136 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. HIV-1 carrying the "Q151M complex" reverse transcriptase (RT) mutations (A62V/V75I/F77L/F116Y/Q151M, or Q151Mc) is resistant to many FDA-approved nucleoside RT inhibitors (NRTIs), but has been considered susceptible to tenofovir disoproxil fumarate (TFV-DF or TDF). 2011 PloS one Abstract HIV A62V;F116Y;F77L;Q151M;V75I;Q151M 73;88;83;94;78;20 77;93;87;99;82;25 RT;NRTI;RT;RT 35;172;58;157 56;177;60;159 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. However, addition of K70Q to the Q151Mc background significantly enhanced resistance to several approved NRTIs, and also resulted in high-level (10-fold) resistance to TFV-DF. 2011 PloS one Abstract HIV K70Q 21 25 NRTI 105 110 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Molecular dynamics simulations suggest that changes in the hydrogen bonding pattern in the polymerase active site of K70Q/Q151Mc RT may contribute to the observed changes in binding and incorporation of TFV-DP. 2011 PloS one Abstract HIV K70Q;Q151M 117;122 121;127 Pol;RT 91;129 101;131 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Pre-steady state kinetic analysis of the recombinant enzymes demonstrated that addition of the K70Q mutation selectively decreases the binding of tenofovir-diphosphate (TFV-DP), resulting in reduced incorporation of TFV into the nascent DNA chain. 2011 PloS one Abstract HIV K70Q 95 99 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Virological analysis showed that HIV with only K70Q was not significantly resistant to TFV-DF. 2011 PloS one Abstract HIV K70Q 47 51 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Although attenuated in comparison to WT virus and single point mutants K65R, L74V and L74I; the double mutant K65R+L74I replicated efficiently in comparison to K65R+L74V mutant. 2011 Virology journal Abstract HIV K65R;K65R;K65R;L74I;L74I;L74V;L74V 71;110;160;86;115;77;165 75;114;164;90;119;81;169 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Analysis of the HIV resistance database has revealed that similar to K65R+L74V, the double mutant K65R+L74I is also rare. 2011 Virology journal Abstract HIV K65R;K65R;L74I;L74V 69;98;103;74 73;102;107;78 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. CONCLUSIONS: The improved replication kinetics of K65R+L74I virus in comparison to K65R+L74V viruses was due to an increase in the processivity of RT containing K65R+L74I mutations. 2011 Virology journal Abstract HIV K65R;K65R;K65R;L74I;L74I;L74V 50;83;161;55;166;88 54;87;165;59;170;92 RT 147 149 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Direct sequencing and sequencing after population cloning showed a more pronounced reversion at codon 65 in viruses containing K65R+L74V mutations in comparison to viruses with K65R+L74I mutations. 2011 Virology journal Abstract HIV K65R;K65R;L74I;L74V 127;177;182;132 131;181;186;136 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In vitro processivity assays showed increased processivity of RT containing K65R+L74I in comparison to K65R+L74V RT. 2011 Virology journal Abstract HIV K65R;K65R;L74I;L74V 76;103;81;108 80;107;85;112 RT;RT 62;113 64;115 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Interestingly, the co-selection of K65R and L74V is rare in clinical settings. 2011 Virology journal Abstract HIV K65R;L74V 35;44 39;48 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. METHODS: Proviral clones containing K65R, L74V, L74I, K65R+L74V and K65R+L74I RT mutations were created in pNL4-3 backbone and viruses were produced in 293T cells. 2011 Virology journal Abstract HIV K65R;K65R;K65R;L74I;L74I;L74V;L74V 36;54;68;48;73;42;59 40;58;72;52;77;46;63 RT 78 80 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The increased replication capacity of K65R+L74I viruses in comparison to K65R+L74V viruses was significant at multiplicity of infection 0.01 (p = 0.0004). 2011 Virology journal Abstract HIV K65R;K65R;L74I;L74V 38;73;43;78 42;77;47;82 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We have previously shown that K65R and L74V are incompatible and a R K reversion occurs at codon 65 during replication of the virus. 2011 Virology journal Abstract HIV K65R;L74V 30;39 34;43 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We sought to compare the impact of L V versus L I change at codon 74 in the background of K65R mutation, on the replication of doubly mutant viruses. 2011 Virology journal Abstract HIV K65R 90 94 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Interestingly, immune activation was observed with both WT and V38E infection suggesting that the two phenomena are likely not interdependent in the mouse model. 2011 Virology journal Abstract HIV V38E 63 67 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. This differential pathogenesis was associated with a lack of bystander apoptosis induction by V38E virus even in the presence of similar levels of infected cells. 2011 Virology journal Abstract HIV V38E 94 98 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. We demonstrate here that a single amino acid change (V38E) altering the cell-to-cell fusion activity of the Env minimizes CD4 loss in humanized mice without altering viral replication. 2011 Virology journal Abstract HIV V38E 53 57 Env 108 111 21257741 Detection of low-level K65R variants in nucleoside reverse transcriptase inhibitor-naive chronic and acute HIV-1 subtype C infections. To substantiate reports of greater emergence of the K65R nucleoside reverse transcriptase inhibitor (NRTI) mutation in human immunodeficiency virus type 1 (HIV-1) subtype C, we examined natural low-level K65R expression in subtype C relative to subtypes B and AE. 2011 The Journal of infectious diseases Abstract HIV K65R;K65R 52;204 56;208 NRTI;NRTI 57;101 89;105 21257741 Detection of low-level K65R variants in nucleoside reverse transcriptase inhibitor-naive chronic and acute HIV-1 subtype C infections. We found low-level K65R of unknown clinical significance in NRTI-naive subtype C-infected women and infants at frequencies above the natural occurrence in subtypes B and AE. 2011 The Journal of infectious diseases Abstract HIV K65R 19 23 NRTI 60 64 21276267 Interplay between HIV entry and transportin-SR2 dependency. However, this dependency on TRN-SR2 is lost when the HIV N74D capsid mutant is pseudotyped with envelopes mediating pH-dependent endocytosis, such as the VSV-G and Ebola virus envelopes. 2011 Retrovirology Abstract HIV N74D 57 61 Env;Env;Capsid 96;176;62 105;185;68 21276267 Interplay between HIV entry and transportin-SR2 dependency. Remarkably, although somewhat less dependent on TRN-SR2 than wild type virus, the N74D capsid mutant carrying the wild type HIV-1 envelope required TRN-SR2 for efficient replication. 2011 Retrovirology Abstract HIV N74D 82 86 Env;Capsid 130;87 138;93 21276267 Interplay between HIV entry and transportin-SR2 dependency. We reanalyzed the HIV-1 N74D capsid mutant in cells transiently or stably depleted of transportin-SR2 and confirm that the N74D capsid mutant is independent of TRN-SR2 when pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). 2011 Retrovirology Abstract HIV N74D 123 127 Capsid;Capsid 29;128 35;134 21282419 Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1. Interestingly, the N348I and M184V double mutation compensated for the reduced NNRTI drug susceptibility observed in the N348I single mutant and marginally improved viral replicative capacity. 2011 Antimicrobial agents and chemotherapy Abstract HIV M184V;N348I;N348I 29;19;121 34;24;126 NNRTI 79 84 21282419 Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1. N348I reduced the susceptibility to all NNRTI drugs across subtypes. 2011 Antimicrobial agents and chemotherapy Abstract HIV N348I 0 5 NNRTI 40 45 21282419 Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1. The replication capacity of all viruses in a variety of cell lines was impaired by N348I. 2011 Antimicrobial agents and chemotherapy Abstract HIV N348I 83 88 21282419 Impact of the N348I mutation in HIV-1 reverse transcriptase on nonnucleoside reverse transcriptase inhibitor resistance in non-subtype B HIV-1. We investigated the effect of N348I alone and with M184V on nonnucleoside reverse transcriptase inhibitor (NNRTI) drug susceptibility and replicative capacity in B and non-B HIV-1 isolates. 2011 Antimicrobial agents and chemotherapy Abstract HIV M184V;N348I 51;30 56;35 NNRTI;NNRTI 60;107 95;112 21282435 Positive impact of HIV-1 gag cleavage site mutations on the virological response to darunavir boosted with ritonavir. We showed the association, in multivariate analysis, between the A431V gag CSM and the virological response, defined as a reduction in plasma HIV-1 RNA to <50 copies/ml at month 3 (P = 0.028). 2011 Antimicrobial agents and chemotherapy Abstract HIV A431V 65 70 Gag 71 74 21282450 Novel HIV-1 protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran, that are potent against multi-PI-resistant HIV-1 variants. When HIV-1(NL4-3) was selected with GRL-1398, four amino acid substitutions--leucine to phenylalanine at a position 10 (L10F), A28S, L33F, and M46I--emerged, ultimately enabling the virus to replicate in the presence of >1.0 muM the compound beyond 57 weeks of selection. 2011 Antimicrobial agents and chemotherapy Abstract HIV A28S;L10F;L10F;L33F;M46I 127;120;77;133;143 131;124;118;137;147 21285456 Predictors for the emergence of the 2 multi-nucleoside/nucleotide resistance mutations 69 insertion and Q151M and their impact on clinical outcome in the Swiss HIV cohort study. Following detection, individuals with Q151M tended to have lower suppression rates and higher mortality rates, relative to control subjects. 2011 The Journal of infectious diseases Abstract HIV Q151M 38 43 21285456 Predictors for the emergence of the 2 multi-nucleoside/nucleotide resistance mutations 69 insertion and Q151M and their impact on clinical outcome in the Swiss HIV cohort study. The 69 insertion and Q151M mutations are multi-nucleoside/nucleotide resistance mutations (MNR). 2011 The Journal of infectious diseases Abstract HIV Q151M 21 26 21285456 Predictors for the emergence of the 2 multi-nucleoside/nucleotide resistance mutations 69 insertion and Q151M and their impact on clinical outcome in the Swiss HIV cohort study. The 69 insertion study (27 control subjects, 14 case patients) identified didanosine exposure as a risk (odds ratio, 5.0 per year; P = .019), whereas the Q151M study (which included 44 control subjects and 25 case patients) detected no associations. 2011 The Journal of infectious diseases Abstract HIV Q151M 154 159 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. In contrast, MK-2048 and L-841,411 produced ~3-fold to 5-fold more ISD than RAL with N155H IN, which is susceptible to these two inhibitors. 2011 Journal of molecular biology Abstract HIV N155H 85 90 IN 91 93 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. The RAL-resistant IN mutant N155H weakly forms the ISD complex in the presence of RAL at ~25% level of wild-type IN. 2011 Journal of molecular biology Abstract HIV N155H 28 33 IN;IN 18;113 20;115 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Among the most prevalent RT mutations, M184V had the fastest rate of reversion from baseline to 2 months (40%), and its reversion was associated with the largest increase in RC. 2011 PloS one Abstract HIV M184V 39 44 RT 25 27 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Between baseline and 2 months of STI, T215F had the fastest rate of reversion (41%) and the reversion of E44D and T69D was associated with the largest changes in RC. 2011 PloS one Abstract HIV E44D;T215F;T69D 105;38;114 109;43;118 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Mutagenesis tree models showed that M184V, when present, was overall the first mutation to revert among all the RT mutations reported in the study. 2011 PloS one Abstract HIV M184V 36 41 RT 112 114 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The highest frequency of concurrent reversion was found for L100I and K103N. 2011 PloS one Abstract HIV K103N;L100I 70;60 75;65 21311104 HIV type-1 drug resistance in treatment-naive patients monitored using minority species assays: a systematic review and meta-analysis. CONCLUSIONS: Additional detection of drug resistance mutations using AS-PCR minority mutation assays vary significantly depending on the mutation examined; however, the most marked increase in detection of resistance mutations was observed for M184V, a mutation seldom detected by standard techniques in drug-naive patients. 2011 Antiviral therapy Abstract HIV M184V 244 249 21311104 HIV type-1 drug resistance in treatment-naive patients monitored using minority species assays: a systematic review and meta-analysis. RESULTS: Our studies revealed an increase in detection of 1.9-fold (95% confidence interval [CI] 1.3-2.7; P < 0.0005) for K103N, 4.4-fold (95% CI 1.2-16.6; P = 0.026) for Y181C, 4.8-fold (95% CI 1.5-15.1; P = 0.008) for L90M and 8.7-fold (95% CI 4.0-18.6; P < 0.0005) for M184V. 2011 Antiviral therapy Abstract HIV K103N;L90M;M184V;Y181C 122;220;272;171 127;224;277;176 21311109 Analysis of drug resistance during HIV RNA viraemia in the MONET trial of darunavir/ritonavir monotherapy. Two patients showed some evidence of PI resistance during transient HIV RNA elevations: one patient in the monotherapy arm had a single DRV mutation (L33F) when HIV RNA was 63 copies/ml (the virus was phenotypically sensitive to DRV [fold change 0.8]) and one PI pretreated patient taking tenofovir disoproxil fumarate/emtricitabine/DRV/r had re-emergence of pre-existing NRTI (M184V) and PI (V82I and L90M) mutations after a short treatment interruption (this virus remained phenotypically sensitive to DRV/r). 2011 Antiviral therapy Abstract HIV L33F;L90M;M184V;V82I 150;402;378;393 154;406;383;398 NRTI;PI;PI;PI 372;37;260;389 376;39;262;391 21311114 Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis. In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). 2011 Antiviral therapy Abstract HIV K103N;Y181C 55;68 60;73 21311114 Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of < 1% of the total viral population. 2011 Antiviral therapy Abstract HIV K103N;Y181C 146;156 152;161 21311115 Multi-nucleoside reverse transcriptase inhibitor resistant HIV type-1 in a patient from Sierra Leone failing stavudine, lamivudine and nevirapine. We report a 33-year-old HIV type-1 (HIV-1)-infected male from Sierra Leone who harboured extensive drug resistance mutations to all nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs, including the multi-NRTI-resistance Q151M complex, K65R, M184I and Y181I, after using standard first-line generic fixed-dose stavudine, lamivudine and nevirapine (Triomune ) for 36 months. 2011 Antiviral therapy Abstract HIV K65R;M184I;Q151M;Y181I 250;256;235;266 254;261;240;271 NRTI;NNRTI;NRTI;NRTI 132;188;177;219 164;197;182;223 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? BACKGROUND: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. 2011 AIDS research and therapy Abstract HIV L76V;L76V 109;260 113;264 PR 65 73 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. 2011 AIDS research and therapy Abstract HIV L76V 37 41 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? CONCLUSIONS: In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. 2011 AIDS research and therapy Abstract HIV L76V 88 92 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. 2011 AIDS research and therapy Abstract HIV L76V 122 126 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002).In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations. 2011 AIDS research and therapy Abstract HIV L76V;L76V;L76V 129;178;223 133;182;227 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? RESULTS: Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options.Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. 2011 AIDS research and therapy Abstract HIV L76V;L76V 115;313 119;317 PI 170 172 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. 2011 AIDS research and therapy Abstract HIV L76V 28 32 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? BACKGROUND: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. 2011 AIDS research and therapy Abstract HIV L76V;L76V 277;428 281;432 PR;PR;PR 27;90;233 35;98;241 21322110 Synthesis and biological evaluation of 6-substituted 5-alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)-ones as potent HIV-1 NNRTIs. Among them, 2-[(4-cyanophenylamino)carbonylmethylthio]-6-(2-chloro-6-fluorobenzyl)-5-ethylpyrimidin-4(3H)-one 4 b6 is one of the compounds endowed with the highest broad-spectrum HIV-1 inhibitory activity, with EC(50) values of 0.19+-0.005 muM against the wild-type virus, 1.05+-0.24 muM (twofold resistance) against the E138K strain, and 2.38+-0.13 muM (4.5-fold resistance) against the Y181C strain. 2011 ChemMedChem Abstract HIV E138K;Y181C 321;388 326;393 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. 2011 Retrovirology Abstract HIV S40F 27 31 Pol 72 75 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. However, the S40F mutation significantly reduces the specific infectivity of released virions. 2011 Retrovirology Abstract HIV S40F 13 17 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site. 2011 Retrovirology Abstract HIV A1V;S40F 79;37 82;41 SP1;SP1;Gag;Capsid 95;144;54;141 98;147;56;143 21325401 Adaptation of subtype a human immunodeficiency virus type 1 envelope to pig-tailed macaque cells. G312V and A204E Env variants continued to require CCR5 for entry but were up to 50- and 200-fold more sensitive to neutralization by IgG1b12 and soluble CD4 and had a 5- to 50-fold increase in their ability to utilize Ptm CD4 compared to their wild-type counterparts. 2011 Journal of virology Abstract HIV A204E;G312V 10;0 15;5 Env 16 19 21325401 Adaptation of subtype a human immunodeficiency virus type 1 envelope to pig-tailed macaque cells. Introduction of G312V and A204E to multiple subtype A Envs and substitution of G312 and A204 with other residues increased entry into Ptm cells by 10- to 100-fold. 2011 Journal of virology Abstract HIV A204E;G312V 26;16 31;21 Env 54 58 21325401 Adaptation of subtype a human immunodeficiency virus type 1 envelope to pig-tailed macaque cells. Two independent mutations in gp120, G312V (V3 loop) and A204E (C2 region), were identified that increased peak virus levels by >100-fold. 2011 Journal of virology Abstract HIV A204E;G312V 56;36 61;41 gp120 29 34 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. Among them, three [7.7%, 95% confidence interval (CI) 1.6-20.9%] had significant INSTI resistance mutations consisting of N155H in two and P145S in one. 2011 AIDS (London, England) Abstract HIV N155H;P145S 122;139 127;144 INSTI 81 86 21334708 Generation and mucosal transmissibility of emtricitabine- and tenofovir-resistant SHIV162P3 mutants in macaques. Both SHIV162p3(M184V) and SHIV162p3(K65R) replicated in vitro at high titers. 2011 Virology Abstract HIV K65R;M184V 36;15 40;20 21334708 Generation and mucosal transmissibility of emtricitabine- and tenofovir-resistant SHIV162P3 mutants in macaques. Mucosal transmissibility studies using a repeat low-dose macaque model of rectal and vaginal transmission showed that both mutants were able to efficiently infect macaques only after the dose was increased to adjust for fitness reductions due to K65R and M184V. 2011 Virology Abstract HIV K65R;M184V 246;255 250;260 21334708 Generation and mucosal transmissibility of emtricitabine- and tenofovir-resistant SHIV162P3 mutants in macaques. Our results in limited number of macaques suggest that the reduction in fitness due to M184V and K65R decreases virus transmissibility, and identify in vitro infectivity parameters that associate with mucosal transmissibility. 2011 Virology Abstract HIV K65R;M184V 97;87 101;92 21334708 Generation and mucosal transmissibility of emtricitabine- and tenofovir-resistant SHIV162P3 mutants in macaques. Virus infectivity to virion particle ratios were 4- and 10-fold lower in SHIV162p3(M184V) and SHIV162p3(K65R), compared to a concurrently generated WT SHIV162p3, respectively. 2011 Virology Abstract HIV K65R;M184V 104;83 108;88 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. These are M20A, E62A/E63A/E64A/E65A (AAAA), P72A/P75A (AXXA), R106A, L164A/L165A, and D174A/D175A. 2011 Journal of neuroimmune pharmacology Abstract HIV E62A;E63A;E64A;E65A;D174A;D175A;L164A;L165A;M20A;P72A;P75A;R106A 16;21;26;31;86;92;69;75;10;44;49;62 20;25;30;35;91;97;74;80;14;48;53;67 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Two recent examples of this alternate approach, F191I for studying PAK2 activation and D123E for the critical residue D123 are discussed. 2011 Journal of neuroimmune pharmacology Abstract HIV D123E;F191I 87;48 92;53 21338326 The role of dynamin in HIV type 1 Env-mediated cell-cell fusion. HIV-1 Env-mediated cell-cell fusion could also be suppressed by a dynamin dominant-negative mutant DNM2(K44A). 2011 AIDS research and human retroviruses Abstract HIV K44A 104 108 Env 6 9 21338625 Within-host co-evolution of Gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case. Among these, we focused on associations between Gag-P453L, the P5' position of the p1/p6 cleavage-site mutation, and PR-D30N/N88D nelfinavir-resistant mutations, and attempted to clarify their virological significance in vitro by constructing recombinant clones. 2011 Antiviral research Abstract HIV D30N;N88D;P453L 120;125;52 124;129;57 Gag;Gag;PR 48;86;117 51;88;119 21338625 Within-host co-evolution of Gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case. Furthermore, database analysis indicated that the P453L(Gag)/D30N(PR)/N88D(PR) association was not specific only to our clinical case, but was common among AIDS patients. 2011 Antiviral research Abstract HIV N88D;D30N;P453L 70;61;50 74;65;55 Gag;PR;PR 56;66;75 59;68;77 AIDS 156 160 21338625 Within-host co-evolution of Gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case. Homology modeling analysis suggested that hydrogen bonds between the 30th PR residue and the R452Gag are disturbed by the D30N(PR) mutation, but the impaired interaction is compensated by P453L(Gag) generating new hydrophobic interactions. 2011 Antiviral research Abstract HIV D30N;P453L 122;188 126;193 Gag;PR;PR 194;74;127 197;76;129 21338625 Within-host co-evolution of Gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case. The results showed that P453L(Gag) has the potential to improve replication capacity and the Gag processing efficiency of viruses with D30N(PR)/N88D(PR) but has little effect on nelfinavir susceptibility. 2011 Antiviral research Abstract HIV D30N;N88D;P453L 135;144;24 139;148;29 Gag;Gag;PR;PR 30;93;140;149 33;96;142;151 21338661 Mechanistic insights into the roles of three linked single-stranded template binding residues of MMLV reverse transcriptase in misincorporation and mispair extension fidelity of DNA synthesis. Mutagenesis of these residues (Y64A, D114A, and R116A) resulted in enzymes with slight to modest changes in polymerase activities. 2011 Gene Abstract HIV D114A;R116A;Y64A 37;48;31 42;53;35 Pol 108 118 21341978 Dynamics of enfuvirtide resistance mutations in enfuvirtide-experienced patients remaining in virological failure under salvage therapy. RESULTS: Genotypic profiles of ENF-resistant variants at ENF discontinuation were as follows: V38A in 3 patients, V38A+N42T+N43D in 1 patient, N43D in 2 patients, and N43K in 1 patient. 2011 Scandinavian journal of infectious diseases Abstract HIV N42T;N43D;N43D;N43K;V38A;V38A 119;124;143;167;94;114 123;128;147;171;98;118 21343443 4'-C-methyl-2'-deoxyadenosine and 4'-C-ethyl-2'-deoxyadenosine inhibit HIV-1 replication. The compounds are also effective against viruses that replicate using reverse transcriptases (RTs) that carry nucleoside reverse transcriptase inhibitor resistance mutations, with the exception of the M184V mutant. 2011 Antimicrobial agents and chemotherapy Abstract HIV M184V 201 206 NRTI;RT;RT 110;70;94 142;92;97 21345162 Rapid development of antiretroviral drug resistance mutations in HIV-infected children less than two years of age initiating protease inhibitor-based therapy in South Africa. Of 41 children without virologic suppression with posttreatment HIV genotype data available, major resistance mutations were found in 32 (78%): 14 (36%) had PI mutations including V82A, M46I, and L90M; 29 (71%) had M184V/I; and three had NNRTI mutations (K103N, Y181C, and G190A). 2011 AIDS research and human retroviruses Abstract HIV G190A;K103N;L90M;M184I;M184V;M46I;V82A;Y181C 273;255;196;215;215;186;180;262 278;260;200;222;222;190;184;267 NNRTI;PI 238;157 243;159 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. Mutations in the polymerase but not in connection or RNase H domains of RT increased in frequency between pretherapy and failure (K103N, P = 0.001; M184I/V, P = 0.016). 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;M184I;M184V 130;148;148 135;155;155 Pol;RT 17;72 27;74 21351434 [In vitro selection and identification of HIV strain which is resistance to two new HIV-1 nonnucleoside reverse transcriptase inhibitors]. At the same time, Y188C (TAT-->TGT) mutation appeared at passage 10. 2010 Yao xue xue bao Abstract HIV Y188C 18 23 Tat 25 28 21351434 [In vitro selection and identification of HIV strain which is resistance to two new HIV-1 nonnucleoside reverse transcriptase inhibitors]. For JB26, there was a L100I (TTA-->ATA) mutation at passage 10. 2010 Yao xue xue bao Abstract HIV L100I 22 27 21351434 [In vitro selection and identification of HIV strain which is resistance to two new HIV-1 nonnucleoside reverse transcriptase inhibitors]. JB25 had amino acid substitution L100I (TTA-->ATA) at passage 6, and then changed into 100 M (ATA-->ATG) at passage 12, which was rare mutation form and had not been reported. 2010 Yao xue xue bao Abstract HIV L100I 33 38 21355515 Analysis of resistance testing in South Trinidad. Poor adherence to antiretroviral therapy (ART) has resulted in the development of multidrug resistant HIV Resistance testing done on 40 samples showed that 64.8% of patients had K103 mutation, 75.6% of patients had M184 mutations and 62% of patients showed resistance to tenofovir suggesting that the K65R mutation was highly likely to be present. 2010 The West Indian medical journal Abstract HIV K65R 301 305 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Resistant D101.12 variants contained at least one substitution in the gp120 V3 region (H308P), plus one of two patterns of gp41 sequence changes involving the fusion peptide (FP) and a downstream residue: G514V+V535M or M518V+F519L+V535M. 2011 Virology Abstract HIV F519L;G514V;H308P;M518V;V535M;V535M 226;205;87;220;211;232 231;210;92;225;216;237 gp120;gp41 70;123 75;127 21357304 Selection and characterization of HIV-1 with a novel S68 deletion in reverse transcriptase. In vitro testing of HIV-1LAI-infected primary human lymphocytes treated with beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (DFC; Dexelvucitabine; Reverset) produced a novel deletion of AGT at codon 68 (S68Delta) alone and in combination with K65R that differentially affects drug response. 2011 Antimicrobial agents and chemotherapy Abstract HIV K65R 250 254 21360548 Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. Of note, the remaining patients on RAL regimens for 14 +- 3 months harbored no or only minor integrase mutations/polymorphisms (T66I, T97A, H114P, S119P, A124S, G163R, I203M, R263K). 2011 Journal of medical virology Abstract HIV A124S;G163R;H114P;I203M;R263K;S119P;T66I;T97A 154;161;140;168;175;147;128;134 159;166;145;173;180;152;132;138 IN 93 102 21360548 Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. The E157Q and E160Q mutational motif was observed in 35% of INI-naive patients harboring subtype C infections, indicating intra-subtype variations. 2011 Journal of medical virology Abstract HIV E157Q;E160Q 4;14 9;19 IN 60 63 HIV infections 89 109 21360548 Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. These variations predicted higher genetic barriers to G140S and G140C in subtypes C, CRF02_AG, and A/CRF01_AE, as well as higher genetic barriers toward acquisition of V151I in subtypes CRF02_AG and A/CRF01_AE. 2011 Journal of medical virology Abstract HIV G140C;G140S;V151I 64;54;168 69;59;173 21360548 Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. Thirteen patients failed raltegravir (RAL)-containing regimens within 8 +- 1 months, in association with the major Q148K/R/H and G140A/S (n = 8/24) or N155H (n = 5/24) mutational pathways. 2011 Journal of medical virology Abstract HIV G140A;G140S;N155H;Q148H;Q148K;Q148R 129;129;151;115;115;115 136;136;156;124;124;124 21366296 Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: new cyclic substituents at indole-2-carboxamide. Against the mutant L100I and K103N RT HIV-1 strains in MT-4 cells, compounds 20, 24-26, 36, and 40 showed antiviral potency superior to that of NVP and EFV. 2011 Journal of medicinal chemistry Abstract HIV K103N;L100I 29;19 34;24 RT 35 37 21366425 Prevalence of HIV type 1 antiretroviral drug resistance mutations in Vietnam: a multicenter study. The most common DRMs observed were M184V, V75A/M, M41L, and K65R (NRTI) and K103N, G190A, and Y181C (NNRTI). 2011 AIDS research and human retroviruses Abstract HIV G190A;K103N;K65R;M184V;M41L;V75A;V75M;Y181C 83;76;60;35;50;42;42;94 88;81;64;40;54;48;48;99 NNRTI;NRTI 101;66 106;70 21371237 Increased detection of the HIV-1 reverse transcriptase M184V mutation using mutation-specific minority assays in a UK surveillance study suggests evidence of unrecognized transmitted drug resistance. Almost all of this increase was accounted for by additional detections of the M184V mutation. 2011 HIV medicine Abstract HIV M184V 78 83 21390473 HIV-1 drug-resistance patterns among patients on failing treatment in a large number of European countries. Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. 2010 Acta dermatovenerologica Alpina, Pannonica, et Adriatica Abstract HIV D67N;K103N;M184V;M41L;T215Y 83;76;63;70;96 87;81;68;74;101 21393163 Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations. Finally, mutation G359S displayed a zidovudine hypersusceptibility phenotype, both per se and when combined with A371V. 2011 The Journal of antimicrobial chemotherapy Abstract HIV A371V;G359S 113;18 118;23 21393163 Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations. Other mutations, such as D488E and Q547K, showed TAM-specific enhancement of resistance to zidovudine. 2011 The Journal of antimicrobial chemotherapy Abstract HIV D488E;Q547K 25;35 30;40 21393163 Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations. Phenotypic analysis of C-terminal mutations showed that N348I, T369V and A371V conferred reduced susceptibility to zidovudine in the context of the TAM-1 and/or TAM-2 pathway, and also conferred dual resistance to nevirapine. 2011 The Journal of antimicrobial chemotherapy Abstract HIV A371V;N348I;T369V 73;56;63 78;61;68 21393163 Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations. RESULTS: Subtype B-infected patient database analysis showed that mutations N348I, A360V/T, T377M and D488E were found to be selected independently of TAMs, whereas mutations R358K, G359S, A371V, A400T, K451R and K512R increased in frequency with the number of TAMs in a dose-dependent fashion. 2011 The Journal of antimicrobial chemotherapy Abstract HIV A360T;A360V;A371V;A400T;D488E;G359S;K451R;K512R;N348I;R358K;T377M 83;83;189;196;102;182;203;213;76;175;92 90;90;194;201;107;187;208;218;81;180;97 21399479 Transmitted antiretroviral drug resistance among newly HIV-1 diagnosed young individuals in Kampala. Two had SDRMs to nucleoside reverse-transcriptase inhibitors (D67G and L210W), three had SDRMs to nonnucleoside reverse transcriptase inhibitors (G190A, G190S, and K101E), and one had SDRMs to protease inhibitors (N88D). 2011 AIDS (London, England) Abstract HIV D67G;G190A;G190S;K101E;L210W;N88D 62;146;153;164;71;214 67;151;158;169;76;218 NNRTI;NRTI;PR 98;17;193 133;49;201 21402840 Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. Here, we employed pre-steady-state kinetics to study the impact of Q151L on substrate and inhibitor binding and the catalytic rate of incorporation. 2011 Antimicrobial agents and chemotherapy Abstract HIV Q151L 67 72 21402840 Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. Incorporation assays with other related compounds and models based on the RT/DNA/GS-9148-diphosphate crystal structure suggest that the 2'-fluoro group of GS-9148 may cause steric hindrance with the side chain of the Q151L mutant. 2011 Antimicrobial agents and chemotherapy Abstract HIV Q151L 217 222 RT 74 76 21402840 Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. Most importantly, we found that the Q151L mutant is unable to incorporate GS-9148 under single-turnover conditions. 2011 Antimicrobial agents and chemotherapy Abstract HIV Q151L 36 41 21402840 Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. Q151L is not stably selected by any of the approved nucleoside or nucleotide analogues; however, it may be a transient intermediate that leads to the related Q151M mutation, which confers resistance to multiple compounds that belong to this class of RT inhibitors. 2011 Antimicrobial agents and chemotherapy Abstract HIV Q151M;Q151L 158;0 163;5 RT 250 252 21402840 Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. The resistance profile of GS-9148 is unique in that the inhibitor can select for the very rare Q151L mutation in HIV-1 RT as a pathway to resistance. 2011 Antimicrobial agents and chemotherapy Abstract HIV Q151L 95 100 RT 119 121 21402840 Mechanism of resistance to GS-9148 conferred by the Q151L mutation in HIV-1 reverse transcriptase. We therefore conclude that Q151L severely compromises binding of GS-9148-diphosphate to RT. 2011 Antimicrobial agents and chemotherapy Abstract HIV Q151L 27 32 RT 88 90 21417755 New trends of primary drug resistance among HIV type 1-infected men who have sex with men in Liaoning Province, China. Included were V32I (0.5%), M46I (2.0%), L90M (2.0%), T215C (0.5%), and Y188L (0.5%). 2011 AIDS research and human retroviruses Abstract HIV L90M;M46I;T215C;V32I;Y188L 40;27;53;14;71 44;31;58;18;76 21417755 New trends of primary drug resistance among HIV type 1-infected men who have sex with men in Liaoning Province, China. L10I (4.5%), V118I/IV (17.4%), and K103R/KR (10.0%) were commonly observed mutations, but do not confer any drug resistance to PIs, NRTIs, and NNRTIs. 2011 AIDS research and human retroviruses Abstract HIV K103K;K103R;V118I;V118V;L10I 35;35;13;13;0 42;42;20;20;4 NNRTI;NRTI;PI 143;132;127 149;137;130 21417755 New trends of primary drug resistance among HIV type 1-infected men who have sex with men in Liaoning Province, China. Only one case carried resistance mutations to all three drug classes (L90M, L10I, and A71T to PI; T215C to NRTI; and Y188L to NNRTI). 2011 AIDS research and human retroviruses Abstract HIV A71T;L10I;L90M;T215C;Y188L 86;76;70;98;117 90;80;74;103;122 NNRTI;NRTI;PI 126;107;94 131;111;96 21417947 Appearance of a single amino acid insertion at position 33 in HIV type 1 protease under a lopinavir-containing regimen, associated with reduced protease inhibitor susceptibility. The L33ins might have a potential role in PI resistance pathways but further investigation in a larger number of clinical samples is required in order to elucidate this resistance mechanism. 2011 AIDS research and human retroviruses Abstract HIV L33ins 4 10 PI 42 44 21439330 Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience. E92Q and Q148H/R were only seen in raltegravir-experienced patients and exclusively infected with subtype B (1.9% vs. 0%, p=0.026, for E92Q and 12.6% vs. 0%, p<0.001, for Q148H/R). 2011 Antiviral research Abstract HIV Q148H;Q148R;E92Q;Q148H;Q148R;E92Q 171;171;135;9;9;0 178;178;139;16;16;4 21439330 Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience. Mutations L101I and T124A were significantly more prevalent in patients with non-B subtypes (66.9% vs. 45.7% for L101I; 61.7% vs. 25.9% for T124A; and 39.1% vs. 12.7% for L101I+T124A; p<0.001 in all cases). 2011 Antiviral research Abstract HIV L101I;T124A;T124A;L101I;L101I;T124A 171;177;140;113;10;20 176;182;144;118;15;25 21439330 Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience. On the contrary, T124A was more frequent in INI-naive than raltegravir-experienced patients (35.1% vs. 2011 Antiviral research Abstract HIV T124A 17 22 IN 44 47 21439330 Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience. Polymorphic changes L101I and T124A were more frequent in HIV-1 non-B than B subtypes. 2011 Antiviral research Abstract HIV L101I;T124A 20;30 25;35 21439330 Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience. S153Y/F was absent in this dataset. 2011 Antiviral research Abstract HIV S153F;S153Y 0;0 7;7 21439330 Resistance associated mutations to dolutegravir (S/GSK1349572) in HIV-infected patients--impact of HIV subtypes and prior raltegravir experience. T124A was more frequent in INI-naive patients but E92Q and Q148H/R were only seen in raltegravir-experienced individuals. 2011 Antiviral research Abstract HIV E92Q;Q148H;Q148R;T124A 50;59;59;0 54;66;66;5 IN 27 30 21441094 Genotypic prediction of resistant mutation in HIV-1 pol gene towards the antiretroviral drugs. One sequence of integrase with minor mutation of E157Q and 9 sequences with other mutations were inferred. 2011 International journal of bioinformatics research and applications Abstract HIV E157Q 49 54 IN 16 25 21441094 Genotypic prediction of resistant mutation in HIV-1 pol gene towards the antiretroviral drugs. Two sequences of protease show the major mutation with mutations sites of I54V and V82A and 8 sequences shown other mutations. 2011 International journal of bioinformatics research and applications Abstract HIV I54V;V82A 74;83 78;87 PR 17 25 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Although the L76V mutation significantly slows the N-terminal autoprocessing of the precursor TFR-PR(L76V) to give rise to the mature PR(L76V), the coselected M46I mutation counteracts the effect by enhancing this rate but renders the TFR-PR(M46I/L76V) precursor less responsive to inhibition by 6 muM LPV while preserving inhibition by SQV and DRV. 2011 Biochemistry Abstract HIV M46I;L76V;L76V;L76V;L76V;M46I 242;247;13;101;137;159 246;251;17;105;141;163 PR;PR;PR 98;134;239 100;136;241 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Crystal structures of PR(L76V) in complexes with DRV and SQV were determined at resolutions of 1.45-1.46 A. 2011 Biochemistry Abstract HIV L76V 25 29 PR 22 24 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Differential scanning calorimetry showed decreases in T(m) of 12C for PR(L76V) in the absence of inhibitors and 5-7C in the presence of inhibitors darunavir (DRV), saquinavir (SQV), and lopinavir (LPV), relative to that of PR. 2011 Biochemistry Abstract HIV L76V 73 77 PR;PR 70;223 72;225 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. SQV shows slightly improved polar interactions with PR(L76V) compared to those with PR. 2011 Biochemistry Abstract HIV L76V 55 59 PR;PR 52;84 54;86 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The bound DRV lacks one hydrogen bond with the main chain of Asp30 in PR(L76V) relative to PR, possibly accounting for the resistance to DRV. 2011 Biochemistry Abstract HIV L76V 73 77 Asp;PR;PR 61;70;91 64;72;93 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The mature HIV-1 protease (PR) bearing the L76V drug resistance mutation (PR(L76V)) is significantly less stable, with a >7-fold higher dimer dissociation constant (K(d)) of 71 +- 24 nM and twice the sensitivity to urea denaturation (UC(50) = 0.85 M) relative to those of PR. 2011 Biochemistry Abstract HIV L76V;L76V 43;77 47;81 PR;PR;PR;PR 17;27;74;272 25;29;76;274 21446917 Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. At temperatures above 52C, K65R and K65R/V75I retained similar levels of DNA polymerase activity to the wild-type HIV-1 group O RT, but were more efficient than HIV-1 group M subtype B and MLV RTs. 2011 The Biochemical journal Abstract HIV K65R;K65R;V75I 27;36;41 31;40;45 Pol;RT;RT 77;128;193 87;130;196 21446917 Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. Forward-mutation assays demonstrated that mutant RTs K65R, R78A and K65R/V75I showed >9-fold increased accuracy in comparison with the wild-type enzyme and were approximately two times more faithful than the MLV RT. 2011 The Biochemical journal Abstract HIV K65R;K65R;R78A;V75I 53;68;59;73 57;72;63;77 RT;RT 49;212 52;214 21446917 Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. However, K65R RT showed a higher tendency to introduce one-nucleotide deletions in comparison with other HIV-1 group O RT variants. 2011 The Biochemical journal Abstract HIV K65R 9 13 RT;RT 14;119 16;121 21446917 Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. K65R, K65R/V75I and R78A RTs showed decreased misinsertion and mispair extension fidelity in comparison with the wild-type enzyme for most base pairs studied. 2011 The Biochemical journal Abstract HIV K65R;R78A;V75I;K65R 6;20;11;0 10;24;15;4 RT 25 28 21446917 Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. R78A had a destabilizing effect on the RT, either in the presence or absence of V75I. 2011 The Biochemical journal Abstract HIV V75I;R78A 80;0 84;4 RT 39 41 21446917 Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. The effects of the mutations K65R, R78A and K65R/V75I on the fidelity of HIV-1 group O RTs were studied using gel-based and M13mp2 lacZ forward-mutation fidelity assays. 2011 The Biochemical journal Abstract HIV K65R;K65R;R78A;V75I 29;44;35;49 33;48;39;53 RT 87 90 21446917 Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. These assays revealed that nucleotide selection is mainly governed by kpol (pol is polymerization) in the case of K65R, whereas both kpol and Kd affect nucleotide discrimination in the case of K65R/V75I. 2011 The Biochemical journal Abstract HIV K65R;K65R;V75I 114;193;198 118;197;202 Pol 76 79 21447875 Transmission of integrase strand-transfer inhibitor multidrug-resistant HIV-1: case report and response to raltegravir-containing antiretroviral therapy. The virus harboured INI drug resistance substitutions (Q148H and G140S) along with multiple reverse transcriptase and protease inhibitor resistance mutations. 2011 Antiviral therapy Abstract HIV G140S;Q148H 65;55 70;61 RT;PR;IN 92;118;20 113;126;23 21449841 Clinical significance of HIV reverse-transcriptase inhibitor-resistance mutations. Among non-nucleoside RT inhibitor (NNRTI)-resistance mutations, K103N was frequently observed, followed by Y181C and G190A. 2011 Future microbiology Abstract HIV G190A;K103N;Y181C 117;64;107 122;69;112 NNRTI;RT 35;21 40;23 21449841 Clinical significance of HIV reverse-transcriptase inhibitor-resistance mutations. In HIV-2 infections, the high prevalence of the Q151M mutation associated with multi-NRTI resistance has been frequently observed. 2011 Future microbiology Abstract HIV Q151M 48 53 NRTI 85 89 HIV infections 3 19 21449841 Clinical significance of HIV reverse-transcriptase inhibitor-resistance mutations. Interestingly, V106M was identified in HIV-1 subtype C as a subtype-specific multi-NNRTI-resistance mutation. 2011 Future microbiology Abstract HIV V106M 15 20 NNRTI 83 88 21449841 Clinical significance of HIV reverse-transcriptase inhibitor-resistance mutations. Several large-scale HIV-1 genotypic analyses have revealed that the most prevalent nucleos(t)ide analog RT inhibitor (NRTI)-resistance mutation is M184V/I followed by a series of thymidine analog-associated mutations: M41L, D67N, K70R, L210W, T215Y/F and K219Q/E. 2011 Future microbiology Abstract HIV D67N;K219E;K219Q;K70R;L210W;M184I;M184V;M41L;T215F;T215Y 224;255;255;230;236;147;147;218;243;243 228;262;262;234;241;154;154;222;250;250 NRTI;RT 118;104 122;106 21451005 Differential persistence of transmitted HIV-1 drug resistance mutation classes. CONCLUSIONS: The rapid replacement of M184V/I mutations is consistent with known fitness costs. 2011 The Journal of infectious diseases Abstract HIV M184I;M184V 38;38 45;45 21451005 Differential persistence of transmitted HIV-1 drug resistance mutation classes. RESULTS: Among 75 individuals with 195 TDR mutations, M184V/I became undetectable markedly faster than did nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence interval [CI], 14.7-408.2; P<.0001), while protease inhibitor and NNRTI replacement rates were similar. 2011 The Journal of infectious diseases Abstract HIV M184I;M184V 54;54 61;61 NNRTI;PR;NNRTI;NNRTI 107;250;154;273 142;258;159;278 21453185 Characterization of HIV type 1 subtype C protease gene: selection of L63P mutation in protease inhibitor-naive Indian patients. Drug resistance genotyping analysis identified 2.6% (1/39) prevalence of major PI resistance (I54T) and 7.7% (3/39) of minor PI resistance (L10I, T74S, and A71T). 2011 AIDS research and human retroviruses Abstract HIV A71T;I54T;L10I;T74S 156;94;140;146 160;98;144;150 PI;PI 79;125 81;127 21453185 Characterization of HIV type 1 subtype C protease gene: selection of L63P mutation in protease inhibitor-naive Indian patients. Selection of T12S, I15V, L19I, M36I, R41K, H69K, L89M, and I93L was observed both in global and Indian subtype C while the L63P mutation was selected in Indian PR sequences. 2011 AIDS research and human retroviruses Abstract HIV H69K;I15V;I93L;L19I;L63P;L89M;M36I;R41K;T12S 43;19;59;25;123;49;31;37;13 47;23;63;29;127;53;35;41;17 PR 160 162 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. 2011 PLoS pathogens Abstract HIV A14C;E45C;P207C;T216C 230;235;91;97 234;239;96;102 Capsid;Capsid 169;110 175;112 21457126 Plasma raltegravir exposure influences the antiviral activity and selection of resistance mutations. Integrase sequences could be obtained for 89 (84%), of whom 30 (33.7%) depicted primary RAL resistance mutations (15 N155H, eight Q148H/R, three Y143R, one E92Q, and three more than one of them). 2012 AIDS research and human retroviruses Abstract HIV E92Q;Q148H;Q148R;Y143R 156;130;130;145 160;137;137;150 IN 0 9 21457133 Drug resistance mutations during structured interruptions of HAART in two HIV-1-infected children. Although the mutation K103R associated with non-nucleoside reverse transcriptase inhibitor resistance was found in two viral rebounds of one patient, the analysis indicated the absence of resistance to RT inhibitors. 2011 Current HIV research Abstract HIV K103R 22 27 NNRTI;RT 44;202 80;204 21459401 Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. Analysis of RCs revealed a significant loss in replication (p=0.004) for viruses containing K65N mutation in comparison to those with K65R mutation. 2011 Virology Abstract HIV K65N;K65R 92;134 96;138 21459401 Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. In addition to K65R, the other mutation observed at HIV-1 RT codon 65 is K65N. 2011 Virology Abstract HIV K65N;K65R 73;15 77;19 RT 58 60 21459401 Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. RT processivity assays showed a significant decrease in the processivity of K65N RT in comparison to K65R RT. 2011 Virology Abstract HIV K65N;K65R 76;101 80;105 RT;RT;RT 0;81;106 2;83;108 21459401 Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. We demonstrated that the significant decrease in RC of K65N viruses is related to the impaired RT processivity of K65N RT in comparison to K65R, and that the selection of the K65R mutation may be favored in clinical use of antiretroviral drugs compared to K65N. 2011 Virology Abstract HIV K65N;K65N;K65N;K65R;K65R 55;114;256;139;175 59;118;260;143;179 RT;RT 95;119 97;121 21459401 Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. While K65N appears to have a phenotypic effect similar to K65R, it is less frequent during clinical trials. 2011 Virology Abstract HIV K65N;K65R 6;58 10;62 21464253 Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens. N348I or T369I was associated with reduced etravirine susceptibility when present with K101P or K103R/V179D. 2011 Antimicrobial agents and chemotherapy Abstract HIV K101P;K103R;T369I;V179D;N348I 87;96;9;102;0 92;101;14;107;5 21464253 Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens. N348I, E399G, and N348I/T369I were associated with reduced etravirine susceptibility when present with K103N, L100I, or Y181C. 2011 Antimicrobial agents and chemotherapy Abstract HIV E399G;K103N;L100I;N348I;T369I;Y181C;N348I 7;103;110;18;24;120;0 12;108;115;23;29;125;5 21464253 Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens. Seventeen CDMs were evaluated: L283I, E312Q, G333D, G333E, G335C, G335D, N348I, A360I, A360T, A360V, V365I, T369I, A371V, A376S, I393L, E399D, and E399G. 2011 Antimicrobial agents and chemotherapy Abstract HIV A360I;A360T;A360V;A371V;A376S;E312Q;E399D;E399G;G333D;G333E;G335C;G335D;I393L;L283I;N348I;T369I;V365I 80;87;94;115;122;38;136;147;45;52;59;66;129;31;73;108;101 85;92;99;120;127;43;141;152;50;57;64;71;134;36;78;113;106 21464253 Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens. The most prevalent CDMs (>10%) were A371V, E399D, A376S, N348I, A360T, G333E, and L283I. 2011 Antimicrobial agents and chemotherapy Abstract HIV A360T;A371V;A376S;E399D;G333E;L283I;N348I 64;36;50;43;71;82;57 69;41;55;48;76;87;62 21464253 Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens. The presence or number of CDMs did not significantly reduce etravirine susceptibility, although small reductions were seen in samples with G333D, N348I, A360V, T369I, and A376S. 2011 Antimicrobial agents and chemotherapy Abstract HIV A360V;A376S;G333D;N348I;T369I 153;171;139;146;160 158;176;144;151;165 21464253 Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens. Virologic responses to an etravirine-containing regimen were slightly diminished when G333D, G335D, or A376S was present, but this was not confirmed in subgroups with higher baseline resistance or without etravirine RAMs. 2011 Antimicrobial agents and chemotherapy Abstract HIV A376S;G333D;G335D 103;86;93 108;91;98 21465559 Understanding the binding mode and function of BMS-488043 against HIV-1 viral entry. The bridging sheet formation cannot be blocked for the W112A mutant of gp120 due to the reduced steric hindrance, in agreement with its significant resistance to the BMS inhibitor. 2011 Proteins Abstract HIV W112A 55 60 gp120 71 76 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. 2011 PLoS medicine Abstract HIV K103N;M184V 104;94 109;99 21469769 Comparative evaluation of the ViroSeq HIV-1 genotyping system and an in-house method for analysis of HIV-1 drug-resistance mutations in China. One NNRTI mutation (the RT mutation Y318F) was reported only by the ViroSeqassay, and this discrepancy resulted from the difference in the pol gene lengths generated by the two systems. 2011 Molecular diagnosis & therapy Abstract HIV Y318F 36 41 NNRTI;Pol;RT 4;139;24 9;142;26 21473930 Selection of HLA-B57-associated Gag A146P mutant by HLA-B *48:01-restricted Gag140-147-specific CTLs in chronically HIV-1-infected Japanese. The sequence analysis of Gag146 in 261 chronically HIV-1-infected Japanese showed the accumulation of the A146P mutation in HLA-B*48:01(+) individuals. 2011 Microbes and infection Abstract HIV A146P 106 111 Gag 25 28 HIV infections 51 65 21473930 Selection of HLA-B57-associated Gag A146P mutant by HLA-B *48:01-restricted Gag140-147-specific CTLs in chronically HIV-1-infected Japanese. These findings together indicate that the A146P mutant is accumulating in Japanese by selection by GI8-specific CTLs. 2011 Microbes and infection Abstract HIV A146P 42 47 21473930 Selection of HLA-B57-associated Gag A146P mutant by HLA-B *48:01-restricted Gag140-147-specific CTLs in chronically HIV-1-infected Japanese. We herein demonstrated Gag140-147(GI8) to be the optimal epitope rather than LI10 and that GI8-specific T cells failed to recognize the A146P mutant virus-infected cells. 2011 Microbes and infection Abstract HIV A146P 136 141 Gag 23 26 21473930 Selection of HLA-B57-associated Gag A146P mutant by HLA-B *48:01-restricted Gag140-147-specific CTLs in chronically HIV-1-infected Japanese. We previously showed the possibility that Gag A146P, which is an escape mutant from HLA-B*57-restricted CTLs, was selected by HLA-B*48:01-restricted Gag138-147(LI10)-specific CTLs in a Japanese cohort in which HLA-B*57 individuals were not detected. 2011 Microbes and infection Abstract HIV A146P 46 51 Gag;Gag 42;149 45;152 21474479 Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients. CONCLUSIONS: T124A and T124A/L101I, more frequent in raltegravir-treated patients, could have some effect on raltegravir response and their presence could play a role in the selection of other mutations conferring S/GSK1349572 resistance. 2011 The Journal of antimicrobial chemotherapy Abstract HIV L101I;T124A;T124A 29;13;23 34;18;28 21474479 Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients. OBJECTIVES: To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients. 2011 The Journal of antimicrobial chemotherapy Abstract HIV L101I;S153Y;T124A;S153F;S153Y;S153Y;T124A;T124A;T124A 133;145;139;103;123;110;90;97;117 138;150;144;108;128;115;95;102;122 IN;IN;IN 69;214;235 78;223;238 21474479 Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients. RESULTS: The T124A mutation alone and the combination T124A/L101I were more frequent in raltegravir-failing patients than in INI-naive patients (39.3% versus 24.5%, respectively, P = 0.005 for T124A and 20.2% versus 10.0%, respectively, P = 0.008 for T124A/L101I). 2011 The Journal of antimicrobial chemotherapy Abstract HIV L101I;L101I;T124A;T124A;T124A;T124A 60;257;13;54;193;251 65;262;18;59;198;256 IN 125 128 21474479 Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients. The S153Y/F mutations were not detected in any integrase sequence (except for S153F alone, only detected in one INI-naive patient). 2011 The Journal of antimicrobial chemotherapy Abstract HIV S153F;S153F;S153Y 4;78;4 11;83;11 IN;IN 47;112 56;115 21482738 Two sorting motifs, a ubiquitination motif and a tyrosine motif, are involved in HIV-1 and simian immunodeficiency virus Nef-mediated receptor endocytosis. All HIV-1 Nef mutants that contain K144R substitution are inactive in MHC-I downregulation. 2011 Journal of immunology (Baltimore, Md. Abstract HIV K144R 35 40 Nef 10 13 21482738 Two sorting motifs, a ubiquitination motif and a tyrosine motif, are involved in HIV-1 and simian immunodeficiency virus Nef-mediated receptor endocytosis. The involvement of tyrosine motif in SIV Nef-mediated CD4 and MHC-I downregulation prompted us to investigate a putative tyrosine motif (Y202Y/F203) in HIV-1 Nef that is conserved among HIV-1 species. 2011 Journal of immunology (Baltimore, Md. Abstract HIV Y202F;Y202Y 136;137 142;142 Nef;Nef 41;158 44;161 21482738 Two sorting motifs, a ubiquitination motif and a tyrosine motif, are involved in HIV-1 and simian immunodeficiency virus Nef-mediated receptor endocytosis. We previously reported that K144 in HIV-1 Nef is di-ubiquitinated, and K144R substitution impairs Nef-mediated CD4 downregulation. 2011 Journal of immunology (Baltimore, Md. Abstract HIV K144R 71 76 Nef;Nef 42;98 45;101 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. METHODS: Infant plasma samples collected at 14 weeks of age were tested using the ViroSeq HIV Genotyping System and a sensitive point mutation assay, LigAmp (for K103N and Y181C). 2011 AIDS (London, England) Abstract HIV K103N;Y181C 162;172 167;177 21491096 The immune response to the RT181-189 epitope in HIV-1-infected patients is associated with viral sequence polymorphism flanking the epitope. We therefore compared IFN-gamma ELISPOT responses to the YV9 epitope (RT181-189) covering the lamivudine resistance mutation, M184V, in HLA-A2(+) antiretroviral treatment (ART)-naive patients (n = 19), to those found in HLA-A2(+) patients with virological failure (n = 15). 2011 Journal of clinical immunology Abstract HIV M184V 126 131 RT 70 72 21498149 Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. Among VF subjects at week 48, 5/26 (19.2%) FTC-treated subjects and 27/77 (35.5%) 3TC-treated subjects developed the M184V/I mutation (P = .145). 2011 HIV clinical trials Abstract HIV M184I;M184V 117;117 124;124 21498149 Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. CONCLUSIONS: The results of this pooled analysis of 3 clinical trials indicate a lower frequency of development of the M184V/I mutation in subjects treated with FTC versus 3TC when combined in regimens containing dual NRTIs and EFV. 2011 HIV clinical trials Abstract HIV M184I;M184V 119;119 126;126 NRTI 218 223 21498149 Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. Multivariate analyses adjusting for baseline viral load, baseline CD4 cell counts, and baseline NRTI resistance showed that treatment with FTC had a significantly lower rate of M184V/I development than treatment with 3TC (odds ratio 0.32; P = .02). 2011 HIV clinical trials Abstract HIV M184I;M184V 177;177 184;184 NRTI 96 100 21498149 Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. PURPOSE: To compare the development of the M184V/I substitution among antiretroviral treatment-naive patients taking the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine (FTC) or lamivudine (3TC) from three phase 3 clinical trials of dual NRTIs (including either FTC or 3TC) plus the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV). 2011 HIV clinical trials Abstract HIV M184I;M184V 43;43 50;50 NNRTI;NRTI;NRTI;NRTI 301;121;166;256 337;153;171;261 21498149 Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. The prevalence of the M184V/I substitution in the FTC or 3TC groups was analyzed using Fisher exact test and in multivariate logistic regression analyses. 2011 HIV clinical trials Abstract HIV M184I;M184V 22;22 29;29 21498149 Reduced emergence of the M184V/I resistance mutation when antiretroviral-naive subjects use emtricitabine versus lamivudine in regimens composed of two NRTIs plus the NNRTI efavirenz. Using the denominator of all subjects treated, 5/522 (1.0%) FTC-treated subjects versus 27/841 (3.2%) 3TC-treated subjects developed the M184V/I substitution (P = .009). 2011 HIV clinical trials Abstract HIV M184I;M184V 137;137 144;144 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. Importantly, the modifications S138A and E148A in the same peptide retained potency against ENF-escape mutants. 2011 Biophysical journal Abstract HIV E148A;S138A 41;31 46;36 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. In this study, ENF-resistant mutants--V38A, N43D, N43D/S138A, Q40H/L45M--were combined with modified inhibitory peptides to identify what we believe to be novel ways to improve peptide efficacy. 2011 Biophysical journal Abstract HIV L45M;N43D;N43D;Q40H;S138A;V38A 67;44;50;62;55;38 71;48;54;66;60;42 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. It is concluded that S138A increased binding of HR2/ENF into grooves and that S138A compensated for electrostatic repulsion between N43D and HR2. 2011 Biophysical journal Abstract HIV N43D;S138A;S138A 132;21;78 136;26;83 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. N43D was more resistant to inhibitory peptides than wild-type, but infectivity was reduced. 2011 Biophysical journal Abstract HIV N43D 0 4 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. The additional mutation S138A (N43D/S138A) increased infectivity and further reduced peptide inhibitory potency. 2011 Biophysical journal Abstract HIV N43D;S138A;S138A 31;36;24 35;41;29 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. The double mutant's increase in potency was greater than the increases from the sum of S138A and E148A individually, showing that these two altered residues synergistically contributed to peptide binding. 2011 Biophysical journal Abstract HIV E148A;S138A 97;87 102;92 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. The six-helix bundle structure indicated that E148A should increase hydrophobic interactions between the coiled-coil and peptide. 2011 Biophysical journal Abstract HIV E148A 46 51 21504732 Increasing hydrophobicity of residues in an anti-HIV-1 Env peptide synergistically improves potency. V38A did not substantially reduce infectivity, but was relatively resistant to inhibitory peptides. 2011 Biophysical journal Abstract HIV V38A 0 4 21504903 Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. Here, we show that the complex Delta67/T69G/K70R enhances ATP-dependent phosphorolytic activity on primers terminated with 3'-azido-3'-deoxythymidine (AZT) or 2',3'-didehydro-2',3'-dideoxythymidine (d4T) both in the presence or absence of TAMs. 2011 The Journal of biological chemistry Abstract HIV T69G;K70R 39;44 43;48 21504903 Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. However, pre-steady-state kinetics revealed only minor differences in selectivity of AZT-triphosphate versus dTTP between deletion-containing RTs and their homologous enzymes having the K219E mutation. 2011 The Journal of biological chemistry Abstract HIV K219E 186 191 RT 142 145 21504903 Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. K219E reduced both ATP- and pyrophosphate-mediated excision of primers terminated with thymidine analogues, only when introduced in RTs bearing Delta69 or S68G/Delta69/K70G, providing further biochemical evidence that explains the lack of association of Delta69 and TAMs in HIV-1 isolates. 2011 The Journal of biological chemistry Abstract HIV K70G;S68G;K219E 168;155;0 172;159;5 RT 132 135 21504903 Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. M41L, T215Y, etc.) while the deletion of Thr-69 (Delta69) is rarely found in isolates containing TAMs. 2011 The Journal of biological chemistry Abstract HIV T215Y;M41L 6;0 11;4 21504903 Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. M41L/T215Y), while Delta69 (or the complex S68G/Delta69/K70G) antagonize the effects of TAMs in ATP-mediated excision. 2011 The Journal of biological chemistry Abstract HIV K70G;S68G;M41L;T215Y 56;43;0;5 60;47;4;10 21504903 Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. Molecular dynamics studies based on models of wild-type HIV-1 RT and mutant Delta69, Delta67/T69G/K70R, and D67N/K70R RTs support a relevant role for Lys/Arg-70 in the excision reaction. 2011 The Journal of biological chemistry Abstract HIV T69G;K70R;D67N;K70R 93;98;108;113 97;102;112;117 RT;RT 62;118 64;121 21504903 Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. The deletion of Asp-67 together with mutations T69G and K70R (Delta67 complex) are usually associated with thymidine analog resistance mutations (TAMs) (e.g. 2011 The Journal of biological chemistry Abstract HIV K70R;T69G 56;47 60;51 Asp 16 19 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. Among the 92 samples sent for resistance testing, 68% had at least one nucleoside reverse transcriptase inhibitor (NRTI) mutation, with M184V being the most common (62%) and with 48% having thymidine analogue mutations. 2011 International health Abstract HIV M184V 136 141 NRTI;NRTI 115;71 119;103 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Both the Envelope mutants tested, V513E and R515A, were equally effective and a combination of Gag and Envelope DN genes significantly enhanced potency. 2011 Virology Abstract HIV R515A;V513E 44;34 49;39 Env;Env;Gag 9;103;95 17;111;98 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Finally, the Y164A/R515A double mutant expressed in a lentiviral vector was effective at inhibiting HIV replication in CD34+ hematopoietic stem cell-derived macrophages, demonstrating the therapeutic potential of our approach. 2011 Virology Abstract HIV R515A;Y164A 19;13 24;18 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Inhibition mediated by R515A could be partially attributed to the Envelope cytoplasmic tail, as deletion of R515A tail partially abrogated its DN effect. 2011 Virology Abstract HIV R515A;R515A 23;108 28;113 Env 66 74 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. We show here that capsid mutants (Q155N and Y164A) are more potent inhibitors of WT HIV than the matrix mutant 1GA. 2011 Virology Abstract HIV Q155N;Y164A 34;44 40;49 Matrix;Capsid 97;18 103;24 21537677 The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. 2011 Memorias do Instituto Oswaldo Cruz Abstract HIV M46I;D30N 62;0 66;4 21537677 The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. 2011 Memorias do Instituto Oswaldo Cruz Abstract HIV D30N;D30N;N88D 66;209;166 70;213;170 PI 237 240 21537677 The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors. The human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. 2011 Memorias do Instituto Oswaldo Cruz Abstract HIV D30N 66 70 PR;PR;PI 48;102;122 56;110;124 21537677 The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. 2011 Memorias do Instituto Oswaldo Cruz Abstract HIV D30N;D30N;N88D 20;149;130 24;153;134 21544209 Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations. Mutations at HIV Gag T186S and T242N reduced VRC, however, in advanced disease only the T242N mutants demonstrated increasing VRC, and were associated with compensatory mutations (p = 0.013). 2011 PloS one Abstract HIV T186S;T242N;T242N 21;31;88 26;36;93 Gag 17 20 21544209 Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations. This is associated with preserved selection pressure at specific viral amino acids (e.g., the T242N polymorphism within the HLA-B*57/5801 restricted TW10 epitope), but with reversion at other sites (e.g., the T186S polymorphism within the HLA-B*8101 restricted TL9 epitope), most notably in Gag and suggestive of "immune relaxation". 2011 PloS one Abstract HIV T186S;T242N 209;94 214;99 Gag 291 294 21545648 Virological response to darunavir in patients infected with HIV is linked to darunavir resistance-associated mutations corrected by the count of mutations with positive impact and is not associated with pharmacological and combined virological/pharmacological parameters. Darunavir GIQ is defined as the ratio between darunavir trough plasma concentration and the count of darunavir resistance-associated mutations (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V) corrected or not corrected by the count of mutations with positive impact (V82A and E35D). 2012 Fundamental & clinical pharmacology Abstract HIV E35D;I47V;I50V;I54L;I54M;I84V;L33F;L76V;L89V;T74P;V11I;V32I;V82A 290;162;168;174;174;194;156;188;200;182;144;150;281 294;166;172;180;180;198;160;192;204;186;148;154;286 21545648 Virological response to darunavir in patients infected with HIV is linked to darunavir resistance-associated mutations corrected by the count of mutations with positive impact and is not associated with pharmacological and combined virological/pharmacological parameters. The count of darunavir resistance-associated mutations corrected by the count of V82A and E35D mutations was the single parameter significantly (P = 0.027) associated with virological response. 2012 Fundamental & clinical pharmacology Abstract HIV E35D;V82A 90;81 94;85 21545648 Virological response to darunavir in patients infected with HIV is linked to darunavir resistance-associated mutations corrected by the count of mutations with positive impact and is not associated with pharmacological and combined virological/pharmacological parameters. This result suggests that both negative and positive impacts of mutations including V82A and E35D should be considered to predict virological response in experienced patients. 2012 Fundamental & clinical pharmacology Abstract HIV E35D;V82A 93;84 97;88 21555824 Natural polymorphisms associated with resistance to new antivirals against HCV in newly diagnosed HIV-HCV-coinfected patients. Although no primary resistance mutations were identified for HCV protease inhibitors or nucleoside analogues, mutations C316Y/N and V499A conferring resistance to some non-nucleoside analogues were found in 6% and 51% of G1 patients, respectively. 2011 Antiviral therapy Abstract HIV C316N;C316Y;V499A 120;120;132 127;127;137 PR 65 73 21557669 Short communication prevalence of susceptibility to etravirine by genotype and phenotype in samples received for routine HIV type 1 resistance testing in the United States. A higher proportion of NNRTI-resistant samples with K103N than without was susceptible to etravirine. 2011 AIDS research and human retroviruses Abstract HIV K103N 52 57 NNRTI 23 28 21557669 Short communication prevalence of susceptibility to etravirine by genotype and phenotype in samples received for routine HIV type 1 resistance testing in the United States. The frequency of individual etravirine mutations and the impact of the K103N mutation on susceptibility to etravirine by genotype were also determined. 2011 AIDS research and human retroviruses Abstract HIV K103N 71 76 21558334 Drug resistance mutations in patients infected with HIV-2 living in Spain. In 24 antiretroviral-experienced patients with virological failure the most frequent major RT resistance mutations were M184V (58%), Q151M (33%) and K65R (21%), which are rarely seen thymidine analogue mutations. 2011 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184V;Q151M 149;120;133 153;125;138 RT 91 93 21558334 Drug resistance mutations in patients infected with HIV-2 living in Spain. In PR the most frequent major changes were V47A (17%), I54M (17%), I82F (13%), L90M (29%) and L99F (29%). 2011 The Journal of antimicrobial chemotherapy Abstract HIV I54M;I82F;L90M;L99F;V47A 55;67;79;94;43 59;71;83;98;47 PR 3 5 21558334 Drug resistance mutations in patients infected with HIV-2 living in Spain. No major mutations associated with drug resistance in HIV-1 were recognized in 29 PR, 20 RT and 5 INT sequences from antiretroviral-naive HIV-2 individuals, although natural polymorphisms with potential effects on susceptibility to PR inhibitors were recognized at 10 positions (L10V/I, V32I, M36I, M46I, I47V, Q58E, A71V/I, G73A, V82I and L89I/V) and for nucleoside reverse transcriptase inhibitors at three positions (T69N, V75I and K219E). 2011 The Journal of antimicrobial chemotherapy Abstract HIV A71I;A71V;G73A;I47V;K219E;L10I;L10V;L89I;L89V;M36I;M46I;Q58E;T69N;V32I;V75I;V82I 317;317;325;305;435;279;279;340;340;293;299;311;420;287;426;331 323;323;329;309;440;285;285;346;346;297;303;315;424;291;430;335 NRTI;PR;PR;RT 356;82;232;89 388;84;234;91 21558334 Drug resistance mutations in patients infected with HIV-2 living in Spain. Two of the three patients who failed on raltegravir had N155H in the INT region. 2011 The Journal of antimicrobial chemotherapy Abstract HIV N155H 56 61 21568760 Surveillance of transmitted HIV type 1 drug resistance among HIV type 1-positive women attending an antenatal clinic in Kakinada, India. As per the 2009 WHO list of mutations for surveillance of transmitted HIVDR, only one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation was detected at K101E from all specimens tested, suggesting a low prevalence (<5%) of resistance to NNRTIs and no mutations were detected at other sites, suggesting a low prevalence (<5%) of resistance to nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) drug classes as well. 2011 AIDS research and human retroviruses Abstract HIV K101E 165 170 NNRTI;NRTI;PR;NNRTI;NNRTI;NRTI;PI 86;354;409;133;249;399;430 121;386;417;138;255;403;432 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. BACKGROUND: The Q151M multi-drug resistance (MDR) pathway in HIV-1 reverse transcriptase (RT) confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors (NRTIs) excluding tenofovir (TDF). 2011 Retrovirology Abstract HIV Q151M 16 21 NRTI;NRTI;RT;RT 177;132;67;90 182;164;88;92 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. CONCLUSIONS: We demonstrate a complex interplay between drug susceptibility and replicative fitness in the acquisition Q151M MDR with serious implications for second-line regimen options. 2011 Retrovirology Abstract HIV Q151M 119 124 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. However, the virus expressing patient-derived Q151M RT at 37 months demonstrated ~44% replicative capacity of that at 4 months. 2011 Retrovirology Abstract HIV Q151M 46 51 RT 52 54 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. In this study we examined the genotypic, phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring. 2011 Retrovirology Abstract HIV Q151M 110 115 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. 2011 Retrovirology Abstract HIV Q151M 61 77 NRTI;RT 115;78 120;80 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The acquisition of the Q151M pathway occurred sequentially over a long period of failing NRTI therapy, and was associated with mutations in multiple RT domains. 2011 Retrovirology Abstract HIV Q151M 23 28 NRTI;RT 89;149 93;151 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The emergence of Q151M MDR occurred in the order A62V, V75I, and finally Q151M on the same genome at 4, 17 and 37 months after initiation of therapy, respectively. 2011 Retrovirology Abstract HIV A62V;Q151M;Q151M;V75I 49;17;73;55 53;22;78;59 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. This was further reduced to ~22% when the Q151M-containing DNA pol domain was expressed with wild-type C-terminal domain, but was then fully compensated by coexpression of the coevolved connection subdomain. 2011 Retrovirology Abstract HIV Q151M 42 58 Pol 63 66 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. We established that fourteen of these mutations are also observed in Q151M-containing sequences submitted to the Stanford University HIV database. 2011 Retrovirology Abstract HIV Q151M 69 85 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. RESULTS: According to G2P false positive rate (FPR) values, among 526 env-sequences analyzed, we further characterized 196 sequences: 105 with FPR <5% and 91 with FPR >70%, for X4-using and R5-using viruses, respectively.Beyond the classical signatures at 11/25 V3 positions (S11S and E25D, R5-tropic viruses; S11KR and E25KRQ, X4-tropic viruses), other specific V3 and gp41 mutations were found statistically associated with the co-receptor usage. 2011 Retrovirology Abstract HIV E25D;E25K;E25Q;E25R;S11K;S11R;S11S 285;320;320;320;310;310;276 289;326;326;326;315;315;281 gp41;Env 370;70 374;73 21569500 Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. RESULTS: Herein, we compared the perturbation of miRNA expression profiles of lymphocytes infected with HIV-1(NL4-3) or derivative strains that are deficient in Tat RNA silencing suppressor activity (Tat K51A substitution) or ablated of the vpr/vif open reading frames. 2011 Retrovirology Abstract HIV K51A 204 208 Vif;Vpr;Tat;Tat 245;241;161;200 248;244;164;203 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The Y712 mutation (Y712C) contributed to at least a 4-fold increase in surface expression for all mutants containing this change. 2011 Retrovirology Abstract HIV Y712C 19 24 21569736 [Screening program on novel drug resistance mutations of subtype B' in human immunodeficiency virus type 1 in China]. RESULTS: Frequencies of 7 mutations at 6 positions, D123E, V292I, K366R, T369A, T369V, A371V and I375V, 2 at DNA polymerase domain and 5 at connection domain of reverse transcriptase (RT) were higher in the treated patients than in the untreated patients. 2011 Zhonghua liu xing bing xue za zhi Abstract HIV A371V;D123E;I375V;K366R;T369A;T369V;V292I 87;52;97;66;73;80;59 92;57;102;71;78;85;64 RT;Pol;RT 161;113;184 182;123;186 21571098 Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms. However, we detected an association of certain Vif alterations (a one amino acid insertion at position 61 and the substitutions A62D/N/S and Q136P) with an accelerated AIDS outcome. 2011 Infection, genetics and evolution Abstract HIV A62D;A62N;A62S;Q136P 128;128;128;141 136;136;136;146 Vif 47 50 AIDS 168 172 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. Assays without RAL suggested that the T97A mutation could rescue the catalytic activity which was impaired by the presence of the Y143C/R mutation. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;Y143C;Y143R 38;130;130 42;137;137 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. FCs of 18 and 100 were observed with the strand transfer assay for IN Y143C/T97A and Y143R/T97A mutations, with IC(50) of 0.625 muM and 2.5 muM, respectively. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;T97A;Y143C;Y143R 76;91;70;85 80;95;75;90 IN 67 69 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. In the strand transfer assay, the IN Y143C or R mutation combined with the secondary mutation T97A severely impaired susceptibility to RAL compared to results with the IN Y143C or R mutation alone. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;Y143C;Y143C 94;37;171 98;42;176 IN;IN 34;168 36;170 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. In these patients, the Y143C/R mutation was associated with the T97A mutation. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;Y143C;Y143R 64;23;23 68;30;30 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. Reigadas et al., PLoS One 5:e10311, 2010), we investigated the genetic pathway and the dynamics of emergence of the Y143C/R mutations in three patients failing RAL-containing regimens. 2011 Antimicrobial agents and chemotherapy Abstract HIV Y143C;Y143R 116;116 123;123 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. The aim of the present biochemical and molecular studies in vitro was to evaluate whether the secondary mutation, T97A, associated with the Y143C/R mutation could increase the level of resistance to RAL and impact IN activities. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;Y143C;Y143R 114;140;140 118;147;147 IN 214 216 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. The combination of the T97A mutation with the primary RAL resistance mutations Y143C/R strongly reduces the susceptibility to RAL and rescues the catalytic defect due to the Y143C/R mutation. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;Y143C;Y143C;Y143R;Y143R 23;79;174;79;174 27;86;181;86;181 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. The HIV-1 integrase (IN) mutations Y143C/R are known as raltegravir (RAL) primary resistance mutations. 2011 Antimicrobial agents and chemotherapy Abstract HIV Y143C;Y143R 35;35 42;42 IN;IN 10;21 19;23 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. This result indicates that the emergence of the Y143C/R/T97A double-mutation pattern in patients is a signature of a high resistance level. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;Y143C;Y143R 56;48;48 60;55;55 21576445 Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A. With a 3'-end processing assay, the 50% inhibitory concentrations (IC(50)) were 1.2 muM, 1.2 muM, 2.4 muM (fold change [FC], 2), and 20 muM (FC, 16.7) for IN wild type (WT), the IN T97A mutation, the IN Y143C/T97A mutation, and the IN Y143R/T97A mutation, respectively. 2011 Antimicrobial agents and chemotherapy Abstract HIV T97A;T97A;T97A;Y143C;Y143R 209;181;241;203;235 213;185;245;208;240 IN;IN;IN;IN 155;178;200;232 157;180;202;234 21576473 Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine. The occurrence of a primary endpoint in the NVP arm was significantly associated with the presence of K103N or Y181C NVP-resistant mutations at frequencies >1%. 2011 Proc Natl Acad Sci U S A Abstract HIV K103N;Y181C 102;111 107;116 21592625 Predicted susceptibility of etravirine in HIV patients experiencing virological failure secondary to non-nucleoside reverse transcriptase inhibitor resistance in Argentina. ETR-RAMs were defined as V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S, and M230L, and were analyzed according to the weighted mutation score to predict susceptibility (Vingerhoets 2008). 2011 Enfermedades infecciosas y microbiologia clinica Abstract HIV A98G;E138A;G190A;G190S;K101E;K101H;K101P;L100I;M230L;V106I;V179D;V179F;V179T;V90I;Y181C;Y181I;Y181V 31;62;91;91;44;44;44;37;104;55;69;69;69;25;80;80;80 35;67;98;98;53;53;53;42;109;60;78;78;78;29;89;89;89 21592625 Predicted susceptibility of etravirine in HIV patients experiencing virological failure secondary to non-nucleoside reverse transcriptase inhibitor resistance in Argentina. Most frequent ETR-RAMs after failure with EFV: G190A (28.1%), K101E (14.9%), L100I (10.5%); and with NVP: Y181C (41.7%), G190A (30.6%) and A98G (13.9%). 2011 Enfermedades infecciosas y microbiologia clinica Abstract HIV A98G;G190A;G190A;K101E;L100I;Y181C 139;47;121;62;77;106 143;52;126;67;82;111 21593146 The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid. Two capsid missense mutant viruses, N74D and P90A, were largely insensitive to NUP153 depletion, as was wild-type HIV-1 when cyclophilin A was depleted simultaneously or when infection was conducted in the presence of cyclosporine A. 2011 Journal of virology Abstract HIV N74D;P90A 36;45 40;49 Capsid 4 10 21599597 Virological response and resistance profiles after 18 to 30 months of first- or second-/third-line antiretroviral treatment: a cross-sectional evaluation in HIV type 1-infected children living in the Central African Republic. Detectable plasma HIV-1 RNA was observed in 53% of children under first-line treatment, and virological failure was diagnosed in 40%, which was associated in 85% of cases with viruses harboring at least one drug-resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI) or nonnucleoside reverse transcriptase inhibitors (NNRTI), and in 36% of cases with at least one major drug-resistance mutation to NRTI or NNRTI when excluding the M184V mutation. 2012 AIDS research and human retroviruses Abstract HIV M184V 450 455 NNRTI;NRTI;NNRTI;NNRTI;NRTI;NRTI 289;235;337;425;280;417 324;267;342;430;284;421 21601230 Ion channel activity of HIV-1 Vpu is dispensable for counteraction of CD317. In contrast, the A14N and A18N mutation did not affect ion channel activity of Vpu, but substantially reduced its ability to support virus release and to down-regulate CD317 from the cell surface. 2011 Virology Abstract HIV A14N;A18N 17;26 21;30 Vpu 79 82 21601230 Ion channel activity of HIV-1 Vpu is dispensable for counteraction of CD317. We examined TM-mutants of three conserved residues: the S23A mutation, which was previously shown to abrogate ion channel function, did not affect Vpu mediated augmentation of virus release. 2011 Virology Abstract HIV S23A 56 60 Vpu 147 150 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. In comparison, virus containing the M184V mutation in reverse transcriptase, which shows decreased replication capacity in vitro, did not have an effect on viral fitness in vivo. 2010 The open medical informatics journal Abstract HIV M184V 36 41 RT 54 75 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Using a bioinformatics-based model to assess the effects of numerous drug resistance mutations, we determined that the D30N mutation in HIV-1 protease had the largest decrease in replication capacity among known protease resistance mutations. 2010 The open medical informatics journal Abstract HIV D30N 119 123 PR;PR 142;212 150;220 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. We found HIV-1 containing the D30N mutation had a significant defect in vivo, showing impaired replication kinetics and a decreased ability to deplete CD4+ thymocytes, compared to the wild-type or virus without the D30N mutation. 2010 The open medical informatics journal Abstract HIV D30N;D30N 30;215 34;219 21620998 Transmitted drug resistance and phylogenetic analysis of HIV CRF01_AE in Northern Vietnam. Four drug resistance mutations; Y181C, L210W, L74I and V75M, were found in four different patients, giving a prevalence of 6.3% (4/63). 2012 Infection, genetics and evolution Abstract HIV L210W;L74I;V75M;Y181C 39;46;55;32 44;50;59;37 21623090 Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India. K103N mutations were seen in 19.4% of women while the Y181C mutation was seen in 5%. 2011 Indian journal of pathology & microbiology Abstract HIV Y181C;K103N 54;0 59;5 21623090 Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India. Sequential blood samples collected at delivery, 7-10 days, 6 weeks, 4 months, 6 months and one year postpartum showed that 81% of K103N mutations and 66.7% of Y181C mutations were detected at 6 weeks postpartum . 2011 Indian journal of pathology & microbiology Abstract HIV K103N;Y181C 130;159 135;164 21628534 Single mutations in HIV integrase confer high-level resistance to raltegravir in primary human macrophages. We show here that during macrophage infection, the presence of a single primary raltegravir resistance mutation (Q148H, Q148R, N155H, or N155S) is sufficient to provide resistance to raltegravir comparable to that seen in viruses expressing both primary and secondary mutations in costimulated CD4(+) T cells. 2011 Antimicrobial agents and chemotherapy Abstract HIV N155H;N155S;Q148H;Q148R 127;137;113;120 132;142;118;125 21632769 Protection against rectal transmission of an emtricitabine-resistant simian/human immunodeficiency virus SHIV162p3M184V mutant by intermittent prophylaxis with Truvada. Despite the high (>100-fold) level of FTC resistance conferred by M184V, all five treated animals were protected from infection, while the five untreated macaques were infected (P = 0.0008). 2011 Journal of virology Abstract HIV M184V 66 71 21632769 Protection against rectal transmission of an emtricitabine-resistant simian/human immunodeficiency virus SHIV162p3M184V mutant by intermittent prophylaxis with Truvada. Five macaques received a dose of Truvada 3 days before exposing them rectally to the simian/human immunodeficiency virus mutant SHIV162p3(M184V), followed by a second dose 2 h after exposure. 2011 Journal of virology Abstract HIV M184V 138 143 21632769 Protection against rectal transmission of an emtricitabine-resistant simian/human immunodeficiency virus SHIV162p3M184V mutant by intermittent prophylaxis with Truvada. Increased susceptibility to tenofovir due to M184V and other factors, including residual antiviral activity by FTC and/or reduced virus fitness due to M184V, may all have contributed to the observed protection. 2011 Journal of virology Abstract HIV M184V;M184V 45;151 50;156 21632769 Protection against rectal transmission of an emtricitabine-resistant simian/human immunodeficiency virus SHIV162p3M184V mutant by intermittent prophylaxis with Truvada. We used a macaque model of HIV transmission to investigate if Truvada maintains prophylactic efficacy against an FTC-resistant isolate containing the M184V mutation. 2011 Journal of virology Abstract HIV M184V 150 155 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. NNRTI mutations detected by genotyping, but not K103N or Y181C mutations detected only by AS-PCR, were associated with viral failure in the switch group. 2011 AIDS (London, England) Abstract HIV K103N;Y181C 48;57 53;62 NNRTI 0 5 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Pretreatment samples were tested using population sequencing and real time allele-specific PCR (AS-PCR) to detect Y181C and K103N minority variants. 2011 AIDS (London, England) Abstract HIV K103N;Y181C 124;114 129;119 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. RESULTS: Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, predominantly Y181C, were detected by either method in 62% of infants less than 6 months of age, in 39% of children 6-12 months of age, 22% 12-18 months, and 16% 18-24 months (P = <0.0001). 2011 AIDS (London, England) Abstract HIV Y181C 88 93 NNRTI;NNRTI 9;56 44;61 21636271 Enantioselective binding of second generation pyrrolobenzoxazepinones to the catalytic ternary complex of HIV-1 RT wild-type and L100I and K103N drug resistant mutants. Unexpectedly (+)-3g was found more potent towards the L100I mutant than towards the wt RT, whereas (+)-3h inhibited the K103N mutant and RT wt with comparable potency. 2011 Bioorganic & medicinal chemistry letters Abstract HIV K103N;L100I 120;54 125;59 RT;RT 87;137 89;139 21637112 Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine. At baseline, only E138A and Q were found at 3.0% and 2.5%, respectively. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138A 18 23 21637112 Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine. E138G, K, and Q were added to the existing etravirine-weighted genotypic score including 17 etravirine resistance-associated mutations. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138G 0 5 21637112 Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine. Site-directed mutants harboring E138A/G/K/Q/R or S showed etravirine fold change values of 2.9, 2.4, 2.6, 3.0, 3.6, and 2.8, respectively. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138A;E138G;E138K;E138Q;E138R 32;32;32;32;32 45;45;45;45;45 21637112 Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine. Virologic response (less than 50 copies/mL) was observed in six of 12 and eight of 10 patients with E138A and E138Q, respectively. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138A;E138Q 100;110 105;115 21646480 The base component of 3'-azido-2',3'-dideoxynucleosides influences resistance mutations selected in HIV-1 reverse transcriptase. In contrast to 3'-azido-ddG, 3'-azido-ddC selected for the V75I mutation in HIV-1 RT that conferred 5.9-fold resistance, compared to the wild-type virus. 2011 Antimicrobial agents and chemotherapy Abstract HIV V75I 59 63 RT 82 84 21646480 The base component of 3'-azido-2',3'-dideoxynucleosides influences resistance mutations selected in HIV-1 reverse transcriptase. Population sequencing of the entire reverse transcriptase (RT) gene identified L74V, F77L, and L214F mutations in the polymerase domain and K476N and V518I mutations in the RNase H domain. 2011 Antimicrobial agents and chemotherapy Abstract HIV F77L;K476N;L214F;L74V;V518I 85;140;95;79;150 89;145;100;83;155 RT;Pol;RT 36;118;59 57;128;61 21646480 The base component of 3'-azido-2',3'-dideoxynucleosides influences resistance mutations selected in HIV-1 reverse transcriptase. Single-genome sequencing analyses of the selected virus revealed a complex population of mutants that all contained L74V and L214F linked to other mutations, including ones not identified during population sequencing. 2011 Antimicrobial agents and chemotherapy Abstract HIV L214F;L74V 125;116 130;120 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. METHODS AND FINDINGS: NVP-resistant HIV-1 harbouring the K103N and/or Y181C resistance mutations in the HIV-1 reverse transcriptase gene was measured from 1 week up to 18 months after NVP single-dose prophylaxis in 29 Ugandan women using allele-specific PCR assays capable of detecting drug-resistant variants representing less than 1% of the whole viral population. 2011 PloS one Abstract HIV K103N;Y181C 57;70 62;75 RT 110 131 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Analysis of RNA secondary structure suggested that the latter was unlikely to impact on K65R development between subtypes and that Streisinger strand slippage during DNA synthesis at the homopolymeric nucleotide stretch of the subtype C K65 region might occur, resulting in misalignment of the primer and template. 2011 PloS one Abstract HIV K65R 88 92 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Consequently, slippage would lead to a deletion of the middle adenine of codon K65 and the production of a -1 frameshift mutation, which upon dislocation and realignment of the primer and template, would lead to development of the K65R mutation. 2011 PloS one Abstract HIV K65R 231 235 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Here, we report that DNA synthesis performed with subtype C templates consistently produced more K65R-containing transcripts than subtype B templates, regardless of the subtype-origin of the RT enzymes employed. 2011 PloS one Abstract HIV K65R 97 101 RT 191 193 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. However, the mechanism underlying this observation and the elevated rates of K65R development remained unknown. 2011 PloS one Abstract HIV K65R 77 81 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Numerous studies have suggested that the K65R reverse transcriptase (RT) mutation develops more readily in subtype C than subtype B HIV-1. 2011 PloS one Abstract HIV K65R 41 45 RT;RT 46;69 67;71 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. These findings provide additional mechanistic evidence for the facilitated development of the K65R mutation in subtype C HIV-1. 2011 PloS one Abstract HIV K65R 94 98 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. We recently showed that this discrepancy lies partly in the subtype C template coding sequence that predisposes RT to pause at the site of K65R mutagenesis. 2011 PloS one Abstract HIV K65R 139 143 RT 112 114 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Importantly, eight patients were already predicted to be resistant to etravirine, the new NNRTI, and three patients harboured the K65R mutation, inducing major resistance to tenofovir. 2011 Journal of the International AIDS Society Abstract HIV K65R 130 134 NNRTI 90 95 21663768 Transmission of HIV drug resistance and non-B subtype distribution in the Spanish cohort of antiretroviral treatment naive HIV-infected individuals (CoRIS). The most prevalent resistance mutations were: T215 revertants (3.8%), D67NG (1.3%), K219QENR (1.2%) and M41L (1%), for NRTIs; K103N (3.2%), for NNRTIs; I54VLMSAT, M46I and L90M (0.7%), for PIs. 2011 Antiviral research Abstract HIV D67G;D67N;I54A;I54L;I54M;I54S;I54T;I54V;K103N;K219E;K219N;K219Q;K219R;L90M;M41L;M46I 70;70;152;152;152;152;152;152;126;84;84;84;84;172;104;163 75;75;161;161;161;161;161;161;131;92;92;92;92;176;108;167 NNRTI;NRTI;PI 144;119;189 150;124;192 21669228 Resistance to raltegravir highlights integrase mutations at codon 148 in conferring cross-resistance to a second-generation HIV-1 integrase inhibitor. N155H, a RAL-associated primary resistance mutation, was selected after IVRS with MK-2048, suggesting similar mechanisms of resistance to RAL and MK-2048. 2011 Antiviral research Abstract HIV N155H 0 5 21669228 Resistance to raltegravir highlights integrase mutations at codon 148 in conferring cross-resistance to a second-generation HIV-1 integrase inhibitor. This was confirmed by phenotypic analysis of 766 clonal viruses harboring IN sequences isolated at the point of virological failure from 106 patients on HAART (including RAL), where mutation Q148H/K/R together with additional secondary mutations conferred reduced susceptibility to both RAL and MK-2048. 2011 Antiviral research Abstract HIV Q148H;Q148K;Q148R 191;191;191 200;200;200 IN 74 76 21678433 Moderate prevalence of transmitted drug resistance and high HIV-1 genetic diversity in patients from Mato Grosso State, Central Western Brazil. Drug resistance mutations were observed in 5.4%: nucleoside reverse transcriptase inhibitor mutations M41L (n = 1), D67N (n = 1), and K219E (n = 1), the non-nucleoside reverse transcriptase inhibitor mutation K103N (n = 1) and the protease inhibitor mutation L90M (n = 1). 2011 Journal of medical virology Abstract HIV D67N;K103N;K219E;L90M;M41L 116;209;134;259;102 120;214;139;263;106 NNRTI;NRTI;PR 153;49;231 189;81;239 21682883 Blocking premature reverse transcription fails to rescue the HIV-1 nucleocapsid-mutant replication defect. We previously reported that two conservative NC mutations, His23Cys and His44Cys, cause premature reverse transcription such that mutant virions contain approximately 1,000-fold more DNA than wild-type virus, and are replication defective. 2011 Retrovirology Abstract HIV H23C;H44C 59;72 67;80 RT;NC 98;45 119;47 21683097 Thiated derivatives of 2',3'-dideoxy-3'-fluorothymidine: synthesis, in vitro anti-HIV-1 activity and interaction with recombinant drug resistant HIV-1 reverse transcriptase forms. The strongest inhibition was observed for K103N and Delta67 mutants and the most potent anti-HIV-1 activity against drug resistant strains and the lowest cytotoxicity was exerted by S4FLTMP and FLTMP which may be regarded as potential anti-HIV/AIDS agents. 2011 Antiviral research Abstract HIV K103N 42 47 AIDS 244 248 21685536 Interpretation of genotypic HIV-1 resistance to darunavir and virological response: validation of available systems and of a new score. The DRV-2009 score V11I+L33F+R41K+I47V+2*I50V+2*I54M+K55R+D60E+L74P+L76V+N88D+2*L89V-L10I/V-I13V-G16E-G48V-F53I/L-I62V-I66F-V77I (<0 indicating susceptibility, 0-1 intermediate resistance and >=2 resistance) correlated with VR in the derivation set (n=132, R=0.395; P<0.001). 2011 Antiviral therapy Abstract HIV D60E;F53I;F53L;G16E;G48V;I13V;I47V;I62V;I66F;K55R;L10I;L10V;L33F;L74P;L76V;N88D;R41K;V11I;V77I;I50V;I54M;L89V 58;107;107;97;102;92;34;114;119;53;85;85;24;63;68;73;29;19;124;42;49;81 62;113;113;101;106;96;38;118;123;57;91;91;28;67;72;77;33;23;128;45;52;84 21689939 Synthesis and biological evaluation of naphthyl phenyl ethers (NPEs) as novel nonnucleoside HIV-1 reverse transcriptase inhibitors. Among them the most active compound 12o showed excellent activities against wild-type HIV-1 with an EC(50) value of 4.60 nM, along with moderate activities against the double mutant strain HIV-1(IIIB) A17 (K103N+Y181C) and HIV-2 strain ROD with an EC(50) value of 0.82 and 4.40 muM, respectively. 2011 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 206;212 211;217 21694603 Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa. Logistic regression assessed factors associated with multiple thymidine analogue mutations (TAMs) and NRTI cross-resistance (>=2 TAMs or Q151M or K65R/K70E). 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;K70E;Q151M 146;151;137 150;155;142 NRTI 102 106 21694603 Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa. NRTI cross-resistance was observed in 48.0% of 183 specimens available for genotypic analysis, comprising >=2 TAMs (37.7%), K65R (7.1%), K70E (3.3%), or Q151M (3.3%). 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;K70E;Q151M 124;137;153 128;141;158 NRTI 0 4 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. nonnucleoside reverse transcriptase inhibitor-DRM were found in 17 of 36 (47.2%) efavirenz recipients, and M184V/I mutation in 14 of 40 (35.0%) lamivudine recipients. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 107;107 114;114 NNRTI 0 35 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. The development of resistance to raltegravir mainly involved three resistance mutations in integrase gene: Q148H/K/R, N155H, and Y143C/H/R. 2010 Infection and drug resistance Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 118;107;107;107;129;129;129 123;116;116;116;138;138;138 IN 91 100 21696230 Studies on adaptability of binding residues and flap region of TMC-114 resistance HIV-1 protease mutants. We provide insight into the molecular basis of TMC-114 resistance major flap mutations (I50V and I54M) in HIV-1 protease. 2011 Journal of biomolecular structure & dynamics Abstract HIV I50V;I54M 88;97 93;101 PR 112 120 21696545 Revealing the drug-resistant mechanism for diarylpyrimidine analogue inhibitors of HIV-1 reverse transcriptase. Diaryltriazine (DATA) and diarylpyrimidine (DAPY) were two category inhibitors with highly potent activity for wild type (wt) and four principal mutant types (L100I, K103N, Y181C and Y188L) of HIV-1 reverse transcriptase (RT). 2011 Chemical biology & drug design Abstract HIV K103N;L100I;Y181C;Y188L 166;159;173;183 171;164;178;188 RT;RT 199;222 220;224 21698125 Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe. Only 2 women had drug resistance mutations; protease I85V and reverse transcriptase Y181C. 2011 PloS one Abstract HIV I85V;Y181C 53;84 57;89 RT;PR 62;44 83;52 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. We found that causal effect estimates of mutations M184V/I (-1.7 log10pVL) and D67N/G (-2.1[3 CD4] and 0.4 log10pVL) were compensated by K103N/S and K219Q/E/N/R. 2011 PloS one Abstract HIV D67G;D67N;K103N;K103S;K219E;K219N;K219Q;K219R;M184I;M184V 79;79;137;137;149;149;149;149;51;51 85;85;144;144;160;160;160;160;58;58 21715484 Replication-competent simian immunodeficiency virus (SIV) Gag escape mutations archived in latent reservoirs during antiretroviral treatment of SIV-infected macaques. Key findings of these studies included: (i) SIV Gag K165R escape mutations emerged in both plasma and cerebrospinal fluid (CSF) during the decaying phase of viremia after HAART initiation before suppression of viral replication, (ii) SIV K165R Gag escape mutations were archived in latent proviral DNA reservoirs, including the brain in animals receiving HAART that suppressed viral replication, and (iii) replication-competent SIV Gag K165R escape mutations were present in the resting CD4(+) T cell reservoir in HAART-treated SIV-infected macaques. 2011 Journal of virology Abstract HIV K165R;K165R;K165R 52;238;436 57;243;441 Gag;Gag;Gag 48;244;432 51;247;435 21715484 Replication-competent simian immunodeficiency virus (SIV) Gag escape mutations archived in latent reservoirs during antiretroviral treatment of SIV-infected macaques. To determine whether HIV escape from MHC class I-restricted CD8(+) T cell control develops during HAART treatment and then enters latent reservoirs in the periphery and central nervous system (CNS), with the potential to emerge as replication-competent virus, we tracked the longitudinal development of the simian immunodeficiency virus (SIV) Gag escape mutation K165R in HAART-treated SIV-infected pigtailed macaques. 2011 Journal of virology Abstract HIV K165R 363 368 Gag 343 346 21715497 Potent and broad anti-HIV-1 activity exhibited by a glycosyl-phosphatidylinositol-anchored peptide derived from the CDR H3 of broadly neutralizing antibody PG16. Finally, the CDR H3 mutations (Y100HF, D100IA, and G7) that were previously shown to compromise the neutralization activity of antibody PG16 also abolished the neutralization activity of GPI-CDR H3(PG16). 2011 Journal of virology Abstract HIV D100A;D100I;Y100F;Y100H 39;39;31;31 45;45;37;37 21719299 Synthesis and biological activity of naphthyl-substituted (B-ring) benzophenone derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors. In particular, the analogue 10i demonstrated the most potent activity against wild-type HIV-1 with an EC50 value of 4.8 nM, and with a high selectivity index up to 10347.9, it also proved to be active against the HIV-1 double mutant strain A17 (K103N+Y181C) with an EC50 value of 2.1 muM. 2011 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 245;251 250;256 21725248 Drug resistance profiles among HIV-1-infected children experiencing delayed switch and 12-month efficacy after using second-line antiretroviral therapy: an observational cohort study in rural China. In the nonnucleoside reverse transcriptase inhibitor class, the most common mutations were K103N/S at 50% and Y181C/I at 48.7%. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;K103S;Y181C;Y181I 91;91;110;110 98;98;117;117 NNRTI 7 42 21725248 Drug resistance profiles among HIV-1-infected children experiencing delayed switch and 12-month efficacy after using second-line antiretroviral therapy: an observational cohort study in rural China. M184V/I was the most common nucleoside reverse transcriptase inhibitor resistance mutation at 77.6%, the mutation rate for >=3 thymidine analogue mutations, Q151M, and K65R were 33%, 12%, and 9%, respectively. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;M184I;M184V;Q151M 168;0;0;157 172;7;7;162 NRTI 28 60 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Allele-specific real-time PCR detected K103N mutants in 15 of the 19 analyzable patients at the end of an off-therapy period while direct sequencing detected mutants in only 6 patients. 2011 PloS one Abstract HIV K103N 39 44 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Allele-specific real-time PCR was used to detect and quantify minor K103N mutants during off-therapy periods. 2011 PloS one Abstract HIV K103N 68 73 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The copy numbers of K103N variants quantified by allele-specific real-time PCR and ultra-deep pyrosequencing agreed closely (rho = 0.89 P<0.0001). 2011 PloS one Abstract HIV K103N 20 25 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The frequency of K103N mutants was <0.1% in 7 patients by allele-specific real-time PCR without further selection, and >0.1% in 8. 2011 PloS one Abstract HIV K103N 17 22 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The half-life of efavirenz was higher (50.5 hours) in the 8 patients in whom K103N emerged (>0.1%) than in the 11 patients in whom it did not (32 hours) (P = 0.04). 2011 PloS one Abstract HIV K103N 77 82 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The K103N mutant frequency was >10% in the remaining 2, treatment failed for one. 2011 PloS one Abstract HIV K103N 4 9 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The pharmacokinetics of efavirenz was assayed to determine whether its variability could influence the emergence of K103N mutants. 2011 PloS one Abstract HIV K103N 116 121 21739439 Resistance to antiretroviral drugs in newly diagnosed, young treatment-naive HIV-positive pregnant women in the province of KwaZulu-Natal, South Africa. Of the 47 samples that were genotyped, only one presented with a K103N mutation, which equates to a prevalence of transmitted HIVDR of <5%. 2011 Journal of medical virology Abstract HIV K103N 65 70 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. Compound 11 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR viral strains, with EC(50) values of 0.086, 0.15, and 0.11 nM, respectively. 2011 European journal of medicinal chemistry Abstract HIV K101E 91 96 21750100 Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. CONCLUSIONS: The M184V mutation can be documented in newly infected individuals, and the alternative hypothesis that this substitution might impact on the ability of HIV to be transmitted is unfounded. 2011 The Journal of antimicrobial chemotherapy Abstract HIV M184V 17 22 21750100 Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. METHODS: To investigate this apparent paradox, we developed an allele-specific real-time PCR (AS-PCR) assay to determine the transmission of M184V in newly infected individuals. 2011 The Journal of antimicrobial chemotherapy Abstract HIV M184V 141 146 21750100 Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. OBJECTIVES: M184V in HIV-1 reverse transcriptase is among the most common mutations in patients failing antiretroviral therapy but is found only rarely in cases of transmitted drug resistance. 2011 The Journal of antimicrobial chemotherapy Abstract HIV M184V 12 17 RT 27 48 21750100 Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. Persistence of M184V may commonly involve linkage to other drug resistance mutations. 2011 The Journal of antimicrobial chemotherapy Abstract HIV M184V 15 20 21750100 Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. RESULTS: M184V transmission may occur to a greater extent than previously thought. 2011 The Journal of antimicrobial chemotherapy Abstract HIV M184V 9 14 21750100 Transmission dynamics of the M184V drug resistance mutation in primary HIV infection. The presence of M184V as a single substitution in newly infected individuals was shown to wane over time, as a likely consequence of reversion and overgrowth by more fit wild-type viruses. 2011 The Journal of antimicrobial chemotherapy Abstract HIV M184V 16 21 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. CONCLUSION: Minority K103N HIV-1 variants, present in acutely HIV-1 infected patients prior to early ART, can reappear and persist after interruption of suppressive ART containing two nucleoside/nucleotide analogue reverse transcriptase inhibitors and a ritonavir-boosted protease inhibitor. 2011 PloS one Abstract HIV K103N 21 26 PR;RT 272;215 280;236 HIV infections 54 76 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Here, we investigated the reappearance of minority K103N and M184V HIV-1 variants in these patients who interrupted efficient early ART after 8-27 months according to the study protocol. 2011 PloS one Abstract HIV K103N;M184V 51;61 56;66 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Minority K103N and M184V HIV-1 variants were quantified in longitudinal plasma samples after treatment interruption by allele-specific real-time PCR. 2011 PloS one Abstract HIV K103N;M184V 9;19 14;24 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Minority K103N HIV-1 variants reappeared after cessation of ART in two of four patients harboring this variant during PHI and even persisted in one of those patients at frequencies similar to the frequency observed prior to ART (<1%). 2011 PloS one Abstract HIV K103N 9 14 HIV infections 118 121 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Minority M184V HIV-1 variants were detected in two patients after ART interruption, one harboring and one not harboring these variants prior to ART. 2011 PloS one Abstract HIV M184V 9 14 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. The K103N mutation did not appear during treatment interruption in any other patient. 2011 PloS one Abstract HIV K103N 4 9 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? In contrast, I54V, G73S and L90M were less prevalent in viruses L76V positive than L76V negative (I54V, 42% vs. 83%, P = 0.01; G73S, 0% vs. 33%, P = 0.02; L90M, 25% vs. 83%, P = 0.0006). 2011 Journal of medical virology Abstract HIV L90M;G73S;G73S;I54V;I54V;L76V;L76V;L90M 155;127;19;13;98;64;83;28 159;131;23;17;102;68;87;32 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? In univariate analyses, of the mutations found in 鈮10% of patients, L89M and Q58E were more prevalent in viruses L76V positive than L76V negative (L89M, 42% vs. 0%, P = 0.0007; Q58E, 50% vs. 25%, P = 0.1). 2011 Journal of medical virology Abstract HIV Q58E;L76V;L76V;L89M;L89M;Q58E 177;114;133;69;148;78 181;118;137;73;151;82 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? L90M, I54V and Q58E were associated with L76V in a multivariate analysis (P < 0.0001, P = 0.002, and P = 0.008, respectively). 2011 Journal of medical virology Abstract HIV I54V;L76V;Q58E;L90M 6;41;15;0 10;45;19;4 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? The HIV-1 protease L76V mutation has been described recently as conferring high-level resistance to lopinavir/ritonavir (LPV/r). 2011 Journal of medical virology Abstract HIV L76V 118 122 PR 109 117 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? Multivariate logistic regressions were used to compare LPV/r-resistant patients infected with virus harboring the L76V mutation or not (L76V positive/L76V negative). 2011 Journal of medical virology Abstract HIV L76V;L76V;L76V 114;136;150 118;141;154 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? One contains the L76V and Q58E mutations and the other contains the L90M and I54V mutations. 2011 Journal of medical virology Abstract HIV I54V;L76V;L90M;Q58E 77;17;68;26 81;21;72;30 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? The aim was to identify the factors and particularly protease mutations associated with the presence of L76V in treatment-experienced patients infected with HIV-1 who have failed virologically an LPV/r-based antiretroviral therapy regimen. 2011 Journal of medical virology Abstract HIV L76V 104 108 PR 53 61 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? The HIV-1 protease L76V mutation has been described recently as conferring high-level resistance to lopinavir/ritonavir (LPV/r). 2011 Journal of medical virology Abstract HIV L76V 19 23 PR 10 18 21755502 Lopinavir/ritonavir resistance in patients infected with HIV-1: two divergent resistance pathways? Twelve patients with virus L76V positive were identified and compared to 24 patients with virus L76V negative selected at random. 2011 Journal of medical virology Abstract HIV L76V;L76V 27;96 31;100 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. All escape clones carried at least one of G36D, V38A, N42D and/or N43D/S in HR1, and accordingly, resistance increased 11- to 2800-fold relative to baseline. 2011 PloS one Abstract HIV G36D;N42D;N43D;N43S;V38A 42;54;66;66;48 46;58;72;72;52 21762812 Two solutions for the same problem: multiple binding modes of pyrrolidine-based HIV-1 protease inhibitors. During the further development of symmetrically disubstituted 3,4-amino-pyrrolidines as human immunodeficiency virus type 1 protease inhibitors, we discovered that, by modification of the P1/P1' moieties of our lead structure, the activity of the inhibitors towards the active-site mutation Ile84Val was altered, however, not being explainable with the initial underlying structure-activity relationship. 2011 Journal of molecular biology Abstract HIV I84V 291 299 PR 124 132 21763494 Functional characterization of human cyclin T1 N-terminal region for human immunodeficiency virus-1 Tat transcriptional activation. However, CycT1 mutants (C261Y, Q50A or F176A) or their chimeric counterparts had lost the transactivation capacity. 2011 Journal of molecular biology Abstract HIV C261Y;F176A;Q50A 24;39;31 29;44;35 21763494 Functional characterization of human cyclin T1 N-terminal region for human immunodeficiency virus-1 Tat transcriptional activation. Moreover, a triple-mutant chimera containing Q46A, Q50A and F176A mutations completely abolished the transcriptional activity, indicating that these amino acid residues are involved through distinct mechanisms. 2011 Journal of molecular biology Abstract HIV F176A;Q46A;Q50A 60;45;51 65;49;55 21763494 Functional characterization of human cyclin T1 N-terminal region for human immunodeficiency virus-1 Tat transcriptional activation. Whereas CycT1 Q46A alone had impaired transcriptional activity, the CycT1(Q46A)-Tat chimeric protein retained almost full activity of the wild-type CycT1. 2011 Journal of molecular biology Abstract HIV Q46A 74 78 Tat 80 83 21763726 The new and less toxic protease inhibitor saquinavir-NO maintains anti-HIV-1 properties in vitro indistinguishable from those of the parental compound saquinavir. The following recombinant viruses were generated and tested: L33F, M46I, G48V, I54V, I84V + L90M, M46I + L90M, G48V + L90M, M46I + I54V + L90M, L33F + M46I + L90M. 2011 Antiviral research Abstract HIV G48V;G48V;I54V;I54V;I84V;L33F;L33F;L90M;L90M;L90M;L90M;L90M;M46I;M46I;M46I;M46I 73;111;79;131;85;61;144;92;105;118;138;158;67;98;124;151 77;115;83;135;89;65;148;96;109;122;142;162;71;102;128;155 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 0 5 NNRTI 158 193 21768506 Expression of an Mg2+-dependent HIV-1 RNase H construct for drug screening. The mutant E706Q (E478Q in RT) was purified under similar conditions and was not active. 2011 Antimicrobial agents and chemotherapy Abstract HIV E478Q;E706Q 18;11 24;16 RT 27 29 21788138 Synthesis and biological evaluation of (+/-)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Furthermore, some of them also exhibited moderate activity against the double mutant strain A(17) (K103N+Y181C) with EC(50) values lower than 5 muM. 2011 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 99;105 104;110 21790471 HIV type 1 molecular epidemiology in pol and gp41 genes among naive patients from Mato Grosso do Sul State, central western Brazil. T-20/gp41 resistance mutations were L44M (n=2) and V38A (n=1). 2012 AIDS research and human retroviruses Abstract HIV L44M;V38A 36;51 40;55 gp41 5 9 21790471 HIV type 1 molecular epidemiology in pol and gp41 genes among naive patients from Mato Grosso do Sul State, central western Brazil. The Pol-RT V75M mutation was detected in two homosexual partners; one patient had the T215S revertant mutation. 2012 AIDS research and human retroviruses Abstract HIV T215S;V75M 86;11 91;15 Pol;RT 4;8 7;10 21791652 Antiretroviral drug resistance in HIV-1-infected patients experiencing persistent low-level viremia during first-line therapy. The most common mutations were M184I/V (14 cases), K103N (9), and M230L (3). 2011 The Journal of infectious diseases Abstract HIV K103N;M184I;M184V;M230L 51;31;31;66 56;38;38;71 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Enzymatic 3TC resistance correlated well with the presence of M184I/V, and reduced NVP susceptibility was strongly associated with the presence of K103N, Y181C/I, Y188L, and G190A/Q. 2011 PloS one Abstract HIV G190A;G190Q;K103N;M184I;M184V;Y181C;Y181I;Y188L 174;174;147;62;62;154;154;163 181;181;152;69;69;161;161;168 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. The sensitivity and specificity for detecting resistance were 97.0% and 96.0% in samples with M184V, and 97.4% and 96.2% for samples with NNRTI mutations, respectively. 2011 PloS one Abstract HIV M184V 94 99 NNRTI 138 143 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Curiously, the Q91N mutant exhibited stringency in discriminating between correct and incorrect nucleotides, suggesting its possible interaction with residues influencing the flexibility of the dNTP binding pocket. 2011 Biochemistry Abstract HIV Q91N 15 19 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. In contrast, both double mutants, Q91A/M184V and Q91N/M184V, are found to be as error prone as the wild-type enzyme. 2011 Biochemistry Abstract HIV M184V;M184V;Q91A;Q91N 39;54;34;49 44;59;38;53 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The efficiency of reverse transcription was severely impaired by nonconservative substitution of Gln with Ala, while conservative substitution of Gln with Asn resulted in an approximately 70% loss of activity, a value similar to that observed with the Y183F mutation. 2011 Biochemistry Abstract HIV Y183F 252 257 RT 18 39 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The loss of polymerase activity from both Q91A and Q91N was significantly improved by a Met to Val substitution at position 184. 2011 Biochemistry Abstract HIV M184V;Q91A;Q91N 88;42;51 127;46;55 Pol 12 22 21802367 HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). 2011 The Lancet. Infectious diseases Abstract HIV K103N;M184V;Y181C;Y181I 47;124;155;155 52;129;162;162 21813613 Loss of protease dimerization inhibition activity of darunavir is associated with the acquisition of resistance to darunavir by HIV-1. A highly DRV-resistant in vitro-selected HIV variant and clinical HIV strains isolated from AIDS patients failing to respond to DRV-containing antiviral regimens typically had the V32I, L33F, I54M, and I84V substitutions in common in protease. 2011 Journal of virology Abstract HIV I54M;I84V;L33F;V32I 192;202;186;180 196;206;190;184 PR 234 242 AIDS 92 96 21813613 Loss of protease dimerization inhibition activity of darunavir is associated with the acquisition of resistance to darunavir by HIV-1. Single amino acid substitutions, including I3A, L5A, R8A/Q, L24A, T26A, D29N, R87K, T96A, L97A, and F99A, disrupted protease dimerization, as examined using an intermolecular fluorescence resonance energy transfer (FRET)-based HIV expression assay. 2011 Journal of virology Abstract HIV D29N;F99A;I3A;L24A;L5A;L97A;R87K;R8A;R8Q;T26A;T96A 72;100;43;60;48;90;78;53;53;66;84 76;104;46;64;51;94;82;58;58;70;88 PR 116 124 21819256 Transmitted HIV resistance to first-line antiretroviral therapy in Lima, Peru. Blood plasma and cells obtained prior to ART initiation were assessed for antiretroviral (ARV) resistance by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant at reverse transcriptase (RT) codons K103N, Y181C, G190A, and M184V and a subset by consensus sequencing. 2012 AIDS research and human retroviruses Abstract HIV G190A;K103N;M184V;Y181C 223;209;234;216 228;214;239;221 RT;RT 175;198 196;200 21819256 Transmitted HIV resistance to first-line antiretroviral therapy in Lima, Peru. This subject had the Y181C mutation detected in both plasma and peripheral blood mononuclear cells (PBMCs) at a concentration of 100% by OLA and consensus sequencing; nevertheless nevirapine-ART suppressed her viral replication. 2012 AIDS research and human retroviruses Abstract HIV Y181C 21 26 21824782 Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC(50) value of 0.009 muM, along with moderate activities against the double RT mutant (K103N+Y181C) HIV-1(III(B)) and HIV-2(ROD) with an EC(50) value of 6.2 and 6.0 muM, respectively. 2011 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 261;267 266;272 RT 250 252 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Although some preexisting drug-resistant variants were detected, N155H, the first major DRM present after initiating RAL therapy, was not detected. 2011 AIDS (London, England) Abstract HIV N155H 65 70 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. No reads contained both the N155H and Q148H drug resistance mutations (DRMs), indicating that the double mutant is not a prominent intermediate, consistent with low fitness. 2011 AIDS (London, England) Abstract HIV N155H;Q148H 28;38 33;43 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. RESULTS: All three patients showed transitions from the N155H pathway to the Q148H/G140S pathway. 2011 AIDS (London, England) Abstract HIV G140S;N155H;Q148H 83;56;77 88;61;82 21835788 Nonnucleoside reverse transcriptase inhibitor-resistant HIV is stimulated by efavirenz during early stages of infection. Additionally, we showed that another NNRTI, nevirapine (NVP), stimulated K101E+G190S virus replication during the early steps of infection similar to EFV, but that the newest NNRTI, etravirine (ETR), did not. 2011 Journal of virology Abstract HIV G190S;K101E 79;73 84;78 NNRTI;NNRTI 37;175 42;180 21835788 Nonnucleoside reverse transcriptase inhibitor-resistant HIV is stimulated by efavirenz during early stages of infection. Reverse transcriptase (RT) genotypes with the NNRTI resistance mutations K101E+G190S are highly resistant to efavirenz (EFV) and can develop during failure of EFV-containing regimens in patients. 2011 Journal of virology Abstract HIV G190S;K101E 79;73 84;78 RT;NNRTI;RT 0;46;23 21;51;25 21835788 Nonnucleoside reverse transcriptase inhibitor-resistant HIV is stimulated by efavirenz during early stages of infection. We also showed that EFV stimulates K101E+Y188L and K101E+V106I virus, but not K101E+L100I, K101E+K103N, K101E+Y181C, or K101E+G190A virus, suggesting that the stimulation is mutation specific. 2011 Journal of virology Abstract HIV G190A;K101E;K101E;K101E;K101E;K101E;K101E;K103N;L100I;V106I;Y181C;Y188L 126;35;51;78;91;104;120;97;84;57;110;41 131;40;56;83;96;109;125;102;89;62;115;46 21835788 Nonnucleoside reverse transcriptase inhibitor-resistant HIV is stimulated by efavirenz during early stages of infection. We determined that EFV stimulates K101E+G190S virus during early infection and does not affect late steps of virus replication, such as increasing the amount of active RT incorporated into virions. 2011 Journal of virology Abstract HIV G190S;K101E 40;34 45;39 RT 168 170 21835788 Nonnucleoside reverse transcriptase inhibitor-resistant HIV is stimulated by efavirenz during early stages of infection. We have previously shown that virus with K101E+G190S mutations can replicate more efficiently in the presence of EFV than in its absence. 2011 Journal of virology Abstract HIV G190S;K101E 47;41 52;46 21837793 Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI-based regimens in the Western Cape, South Africa. Also reported are associations of therapy choice, prolonged virologic failure, and concurrent HIV viral load and CD4 count with the presence of M184I/V, TAMs, K65R, and resistance to ETV. 2011 Journal of medical virology Abstract HIV K65R;M184I;M184V 159;144;144 163;151;151 21837793 Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI-based regimens in the Western Cape, South Africa. In order to describe resistance patterns by genotypic testing, at the time of first-line ART failure and to describe associations with having M184I/V, K65R, three or more thymidine analog mutations (TAMs) and etravirine (ETV) resistance, the prevalence of antiretroviral drug resistance associated mutations in a cross-sectional study, at two South African public health clinic settings, at the time of virologic failure (HIV-1 RNA load >400 copies/ml) are described. 2011 Journal of medical virology Abstract HIV K65R;M184I;M184V 151;142;142 155;149;149 21837793 Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI-based regimens in the Western Cape, South Africa. Of 167 adult patients with virologic failure on first-line ART, 28 (17%) had no resistance, 137 (82%) had NNRTI resistance, 101 (60%) M184I/V, 20 (12%) TAMs, of which 4 had 3 or more TAMs, and 7 (4%) had K65R, of which 6 were on D4T and one on AZT. 2011 Journal of medical virology Abstract HIV M184I;M184V;K65R 134;134;204 141;141;208 NNRTI 106 111 21837878 Prevalence of drug-resistant mutations in newly diagnosed drug-naive HIV-1-infected individuals in a treatment site in the waterberg district, limpopo province. RESULTS: A drug-resistant mutation prevalence of 3.5% (95% confidence interval 0.019796-0.119077) comprising Y181C and L33F was observed; 98% of the viruses were HIV-1 subtype C on the protease (PR) and reverse transcriptase (RT) gene regions. 2011 South African medical journal Abstract HIV L33F;Y181C 119;109 123;114 RT;PR;PR;RT 203;185;195;226 224;193;197;228 21844300 A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. 2011 The Journal of infectious diseases Abstract HIV A376S 0 5 21844300 A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses. 2011 The Journal of infectious diseases Abstract HIV A376S 32 37 NNRTI 107 112 21844300 A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. CONCLUSIONS: The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure to nevirapine-based ART. 2011 The Journal of infectious diseases Abstract HIV A376S 17 22 RT 73 75 21844300 A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. Enzymatic assays also determined the effects of A376S on nevirapine and template-primer binding to HIV-1 RT. 2011 The Journal of infectious diseases Abstract HIV A376S 48 53 RT 105 107 21844300 A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. Preexisting A376S was associated with an increased risk of virological failure to nevirapine (relative hazard [RH] = 10.4; 95% confidence interval [CI], 2.0-54.7), but it did not affect efavirenz outcome the same way (RH = 0.5; 95% CI, 0.1-2.2) (P value for interaction = .013). 2011 The Journal of infectious diseases Abstract HIV A376S 12 17 21849432 Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1. Clinical trials of RPV administered with lamivudine or emtricitabine showed the emergence of E138K together with M184I, which confers lamivudine and emtricitabine resistance in most patients with virologic failure. 2011 Journal of virology Abstract HIV E138K;M184I 93;113 98;118 21849432 Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1. Fitness profiles and growth competition experiments showed that the E138K/M184I mutant had a significant replicative advantage over the E138K/M184V mutant in the presence of etravirine and lamivudine. 2011 Journal of virology Abstract HIV E138K;E138K;M184I;M184V 68;136;74;142 73;141;79;147 21849432 Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1. Resistance to the nonnucleoside reverse transcriptase inhibitors etravirine and rilpivirine (RPV) is conferred by the E138K mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). 2011 Journal of virology Abstract HIV E138K 118 123 NNRTI;RT;RT 18;180;203 53;201;205 21849432 Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1. The RC of the E138K/M184I mutant in the presence of etravirine was significantly greater than that of the E138K and E138K/M184V mutants; the RC of the double mutants was greater than that of the M184I or M184V mutant. 2011 Journal of virology Abstract HIV E138K;E138K;E138K;M184I;M184I;M184V;M184V 14;106;116;20;195;122;204 19;111;121;25;200;127;209 21849432 Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1. The virion-associated RT activity of the E138K, M184I, or M184V virus was significantly reduced compared to that of the WT, whereas the RT activity of the E138K/M184I virus was significantly greater than that of the WT or E138K/M184V virus. 2011 Journal of virology Abstract HIV E138K;E138K;E138K;M184I;M184I;M184V;M184V 41;155;222;161;48;228;58 46;160;227;166;53;233;63 RT;RT 22;136 24;138 21849432 Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1. These results suggest that the E138K and M184I/V mutations are mutually compensatory and may explain the frequent occurrence of E138K/M184I after the virologic failure of rilpivirine-, lamivudine-, and emtricitabine-containing regimens. 2011 Journal of virology Abstract HIV E138K;E138K;M184I;M184I;M184V 31;128;134;41;41 36;133;139;48;48 21849432 Interaction of reverse transcriptase (RT) mutations conferring resistance to lamivudine and etravirine: effects on fitness and RT activity of human immunodeficiency virus type 1. To understand why M184I was favored over M184V, we determined the drug susceptibility, infectivity, relative fitness, and reverse transcriptase activity of HIV-1 carrying E138K/M184I or E138K/M184V mutations. 2011 Journal of virology Abstract HIV E138K;E138K;M184I;M184I;M184V;M184V 186;171;177;18;192;41 191;176;182;23;197;46 RT 122 143 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. E138K restored viral replication capacity (RC) in the presence of M184I/V, and this was confirmed in cell-free RT processivity assays. 2011 Journal of virology Abstract HIV M184I;M184V;E138K 66;66;0 73;73;5 RT 111 113 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. In contrast, M184I/V resulted in an increased K(m) for dNTPs compared to those for WT RT. 2011 Journal of virology Abstract HIV M184I;M184V 13;13 20;20 RT 86 88 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. Recently, several phase 3 clinical trials (ECHO and THRIVE) showed that E138K and M184I were the most frequent mutations to emerge in patients who failed therapy with rilpivirine (RPV) together with two nucleos(t)ide reverse transcriptase inhibitors, emtricitabine (FTC) and tenofovir (TDF). 2011 Journal of virology Abstract HIV E138K;M184I 72;82 77;87 NRTI 203 238 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. RT enzymes containing E138K, E138K/184I, or E138K/184V exhibited higher processivity than WT RT at low dNTP concentrations. 2011 Journal of virology Abstract HIV E138K;E138K;E138K 22;29;44 27;34;49 RT;RT 0;93 2;95 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. Steady-state kinetic analysis demonstrated that the E138K mutation resulted in decreased K(m)s for dNTPs. 2011 Journal of virology Abstract HIV E138K 52 57 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. Structural modeling shows that the addition of E138K to M184I/V promotes tighter dNTP binding. 2011 Journal of virology Abstract HIV E138K;M184I;M184V 47;56;56 52;63;63 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. The results of phenotyping showed that viruses containing both the E138K and M184V mutations were more resistant to each of FTC, 3TC, and ETR than viruses containing E138K and M184I. 2011 Journal of virology Abstract HIV E138K;E138K;M184I;M184V 67;166;176;77 72;171;181;82 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. These results indicate that the E138K mutation compensates for both the deficit in dNTP usage and impairment in replication capacity by M184I/V. 2011 Journal of virology Abstract HIV E138K;M184I;M184V 32;136;136 37;143;143 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. To investigate the basis for the copresence of E138K and M184I, we generated recombinant mutated and wild-type (WT) reverse transcriptase (RT) enzymes and HIV-1(NL4-3) infectious clones. 2011 Journal of virology Abstract HIV E138K;M184I 47;57 52;62 RT;RT 116;139 137;141 21849444 Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. Viruses with E138K displayed only modest resistance to ETR, little resistance to efavirenz (EFV), and no resistance to either FTC or 3TC. 2011 Journal of virology Abstract HIV E138K 13 18 21851324 Transmitted drug resistance among antiretroviral-naive patients with established HIV type 1 infection in Santo Domingo, Dominican Republic and review of the Latin American and Caribbean literature. The most commonly identified SDRM was K103N. 2012 AIDS research and human retroviruses Abstract HIV K103N 38 43 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. 2011 Journal of the American Chemical Society Abstract HIV Y181C;Y181C 68;79 77;84 RT 102 104 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. 2011 Journal of the American Chemical Society Abstract HIV Y181C 151 156 NNRTI 89 95 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. CONCLUSION: This study confirms that HIV-2 resistance to RAL is due to the N155H, G140S/Q148R or E92Q/Y143C mutations. 2011 Retrovirology Abstract HIV E92Q;G140S;N155H;Q148R;Y143C 97;82;75;88;102 101;87;80;93;107 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Conversely, Y143C alone did not confer resistance to RAL unless E92Q is also present. 2011 Retrovirology Abstract HIV E92Q;Y143C 64;12 68;17 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Finally, the Y143C mutation counteracts the resistance conferred by the N155H mutation, probably accounting for the lack of detection of these mutations together in a single genome. 2011 Retrovirology Abstract HIV N155H;Y143C 72;13 77;18 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. For Y143C to confer resistance in vitro, it must be accompanied by E92Q, which therefore plays a more important role in the HIV-2 context than in the HIV-1 context. 2011 Retrovirology Abstract HIV E92Q;Y143C 67;4 71;9 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Furthermore, the introduction of the Y143C mutation into the N155H resistant background decreased the resistance level of enzymes containing the N155H mutation. 2011 Retrovirology Abstract HIV N155H;N155H;Y143C 61;145;37 66;150;42 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Recent studies have shown that HIV-2 resistance to raltegravir involves one of three resistance mutations, N155H, Q148R/H and Y143C, previously identified as resistance determinants in the HIV-1 integrase coding sequence. 2011 Retrovirology Abstract HIV N155H;Q148H;Q148R;Y143C 107;114;114;126 112;121;121;131 IN 195 204 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The G140S mutation conferred little resistance, but compensated for the catalytic defect due to the Q148R mutation. 2011 Retrovirology Abstract HIV G140S;Q148R 4;100 9;105 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The genomes of the resistant strains were cloned and three patterns involving N155H, G140S/Q148R or Y143C mutations were identified. 2011 Retrovirology Abstract HIV G140S;N155H;Q148R;Y143C 85;78;91;100 90;83;96;105 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The N155H and G140S/Q148R mutations make similar contributions to resistance in both HIV-1 and HIV-2, but Y143C is not sufficient to account for the resistance of HIV-2 genomes harboring this mutation. 2011 Retrovirology Abstract HIV G140S;N155H;Q148R;Y143C 14;4;20;106 19;9;25;111 21857318 Genotypic analysis of the gp41 HR1 region from HIV-1 isolates from enfuvirtide-treated and untreated patients. CONCLUSIONS: The V38A substitution in the gp41 HR region was the most common resistance mutation among ENF-treated patients and was associated with increased viral load. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV V38A 17 21 gp41 42 46 21857318 Genotypic analysis of the gp41 HR1 region from HIV-1 isolates from enfuvirtide-treated and untreated patients. Overall, 17% of all isolates showed the N42S polymorphism related to ENF hypersusceptibility. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N42S 40 44 21857318 Genotypic analysis of the gp41 HR1 region from HIV-1 isolates from enfuvirtide-treated and untreated patients. The V38A substitution was the most frequent among treatment-experienced patients followed by the G36D/E, N42D, and V38M substitutions. 2011 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G36D;G36E;N42D;V38A;V38M 97;97;105;4;115 103;103;109;8;119 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. RAV-1 IN shows a standard activity for integration and its CCD differs in sequence from that of RSV-A by a single accessible residue in position 182 (substitution A182T). 2011 PloS one Abstract HIV A182T 163 168 IN 6 8 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. We have subsequently determined the structure of the mutant A182T of RAV-1 IN CCD and obtained a RSV-A IN CCD-like structure with two pairs of buried alpha-helices at the interface. 2011 PloS one Abstract HIV A182T 60 65 IN;IN 75;103 77;105 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. All N348 mutant RTs exhibited decreased nevirapine susceptibility, although the N348I and N348L mutations conferred higher fold resistance values compared to N348A and N348Q. 2011 Retrovirology Abstract HIV N348A;N348I;N348L;N348Q 158;80;90;168 163;85;95;173 RT 16 19 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. BACKGROUND: N348I in HIV-1 reverse transcriptase (RT) confers resistance to zidovudine (AZT) and nevirapine. 2011 Retrovirology Abstract HIV N348I 12 17 RT;RT 27;50 48;52 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Biochemical studies demonstrated that N348I indirectly increases AZT resistance by decreasing the frequency of secondary ribonuclease H (RNase H) cleavages that reduce the RNA/DNA duplex length of the template/primer (T/P) and diminish the efficiency of AZT-monophosphate (MP) excision. 2011 Retrovirology Abstract HIV N348I 38 43 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. By contrast, the N348A and N348Q RTs exhibited RNase H cleavage profiles and AZT-MP excision activities similar to the wild-type enzyme. 2011 Retrovirology Abstract HIV N348A;N348Q 17;27 22;32 RT 33 36 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. CONCLUSIONS: This study demonstrates that N348I-mediated AZT and nevirapine resistance is due to the mutation in the p51 subunit of RT. 2011 Retrovirology Abstract HIV N348I 42 47 RT 132 134 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. N348I and N348L significantly decreased the frequency of secondary RNase H cleavages and increased the enzyme's ability to excise AZT-MP. 2011 Retrovirology Abstract HIV N348L;N348I 10;0 15;5 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. To validate this model, we introduced the N348I, N348L, N348A and N348Q mutations into RT and purified enzymes that contained subunit-specific mutations. 2011 Retrovirology Abstract HIV N348A;N348I;N348L;N348Q 56;42;49;66 61;47;54;71 RT 87 89 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In all in vitro selections, one of four mutations was selected: Gag V362I, A364V, S368N or V370A. 2011 Retrovirology Abstract HIV A364V;S368N;V362I;V370A 75;82;68;91 80;87;73;96 Gag 64 67 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. 2011 Virology journal Abstract HIV A98G;K103N;K70R;L100I 49;138;40;98 53;143;44;103 RT 6 8 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Only one patient, CRF02_AG, showed major resistance mutation L90M. 2011 Virology journal Abstract HIV L90M 61 65 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. 2011 Virology journal Abstract HIV K20I;K20R;L63P;M36I 128;128;118;112 134;134;122;116 PR 71 79 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Three patients had other mutations such as V118I, E138A and V90I. 2011 Virology journal Abstract HIV E138A;V118I;V90I 50;43;60 55;48;64 21875140 Combined approach using ligand efficiency, cross-docking, and antitarget hits for wild-type and drug-resistant Y181C HIV-1 reverse transcriptase. New hits against HIV-1 wild-type and Y181C drug-resistant reverse transcriptases were predicted taking into account the possibility of some of the known metabolism interactions. 2011 Journal of chemical information and modeling Abstract HIV Y181C 37 42 RT 58 80 21875151 Insight into the inhibitory mechanism and binding mode between D77 and HIV-1 integrase by molecular modeling methods. In this paper, the binding modes between the wild type integrase core domain (ICD) and the W131A mutant ICD with the benzoic acid derivative--D77 were investigated using the molecular docking combined with molecular dynamics (MD) simulations. 2011 Journal of biomolecular structure & dynamics Abstract HIV W131A 91 96 IN 55 64 21875151 Insight into the inhibitory mechanism and binding mode between D77 and HIV-1 integrase by molecular modeling methods. The result of MD simulations showed that the W131A substitution affected the flexibility of the region 150-167 in both the monomer A and B of the mutant type ICD. 2011 Journal of biomolecular structure & dynamics Abstract HIV W131A 45 50 21875599 RNA interference as a tool for exploring HIV-1 robustness. Importantly, the addition of a second-generation siRNA that matched the D30N mutation restored viral inhibition and delayed development of escape variants. 2011 Journal of molecular biology Abstract HIV D30N 72 76 21875599 RNA interference as a tool for exploring HIV-1 robustness. Passages performed with both siRNAs prevented the emergence of the D30N escape mutant and forced the virus to develop new escape routes. 2011 Journal of molecular biology Abstract HIV D30N 67 71 21875599 RNA interference as a tool for exploring HIV-1 robustness. The most common escape route was the D30N mutation. 2011 Journal of molecular biology Abstract HIV D30N 37 41 21875619 Prediction of drug-resistance in HIV-1 subtype C based on protease sequences from ART naive and first-line treatment failures in North India using genotypic and docking analysis. Among the first-line treatment failures, an isolate from one patient showed L33F, I47T, M46G, and G48E mutations conferring intermediate resistance to saquinavir (SQV) and lopinavir (LPV). 2011 Antiviral research Abstract HIV G48E;I47T;L33F;M46G 98;82;76;88 102;86;80;92 21875619 Prediction of drug-resistance in HIV-1 subtype C based on protease sequences from ART naive and first-line treatment failures in North India using genotypic and docking analysis. No major mutations were seen in the PR sequences in isolates from treatment-naive individuals, although isolates from two patients had T74S mutation, known to be associated with reduced susceptibility to nelfinavir (NFV) and a combination of M36I, H69K and L89M mutations found in isolates from 77 patients (59.7%), considered to be conferring resistance to tipranavir (TPV) according to ANRS algorithm. 2011 Antiviral research Abstract HIV H69K;L89M;M36I;T74S 248;257;242;135 252;261;246;139 PR 36 38 21876054 MK-0536 inhibits HIV-1 integrases resistant to raltegravir. It is also effective against INs that carry the three main RAL resistance mutations (Y143R, N155H, and to a lesser extent G140S-Q148H) and against the G118R mutant. 2011 Antimicrobial agents and chemotherapy Abstract HIV G118R;G140S;N155H;Q148H;Y143R 151;122;92;128;85 156;127;97;133;90 IN 29 32 21877906 Transmitted drug-resistant HIV type 1 remains prevalent and impacts virologic outcomes despite genotype-guided antiretroviral therapy. K103N/S was the most frequent (n=77). 2012 AIDS research and human retroviruses Abstract HIV K103N;K103S 0;0 7;7 21890537 'Sentinel' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing. METHODS: We focused our attention on three reverse transcriptase (RT) mutations (T69S, L210M and K103R) easily detected by standard population sequencing [i.e. 2011 The Journal of antimicrobial chemotherapy Abstract HIV K103R;L210M;T69S 97;87;81 102;92;85 RT;RT 43;66 64;68 21890537 'Sentinel' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing. Moreover, the presence of L210M or T69S viruses by GRT significantly correlated with that of minority thymidine analogue mutations by UDPS (6/20 patients carrying HIV-1 strains with T69S/L210M versus 0/20 patients carrying HIV-1 having K103R or none of these mutations; P = 0.03). 2011 The Journal of antimicrobial chemotherapy Abstract HIV K103R;L210M;L210M;T69S;T69S 236;187;26;35;182 241;192;31;39;186 21890537 'Sentinel' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing. No association was found for K103R by GRT. 2011 The Journal of antimicrobial chemotherapy Abstract HIV K103R 29 34 21890537 'Sentinel' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing. Notably, T69S and L210M (but not K103R or control viruses) were associated with GRT minority drug-resistant variants with a prevalence >1% (3/10 and 4/10 versus 0/20 in K103R and controls; P = 0.03 and P = 0.008, respectively). 2011 The Journal of antimicrobial chemotherapy Abstract HIV K103R;K103R;L210M;T69S 33;169;18;9 38;174;23;13 21890537 'Sentinel' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing. Patients carrying HIV-1 strains with T69S and L210M by GRT showed a trend to greater infection by minority drug-resistant variants than control patients infected by HIV-1 without these mutations (5/10 and 7/10 versus 3/10; P = not significant). 2011 The Journal of antimicrobial chemotherapy Abstract HIV L210M;T69S 46;37 51;41 21896288 HIV-1 reverse transcriptase connection subdomain mutations involved in resistance to approved non-nucleoside inhibitors. Examples are Y318F or W, N348I, A376S and T369I or V. 2011 Antiviral research Abstract HIV A376S;N348I;T369I;Y318F 32;25;42;13 37;30;47;18 21896288 HIV-1 reverse transcriptase connection subdomain mutations involved in resistance to approved non-nucleoside inhibitors. Moreover, those mutations could also modulate RNase H activity not only during DNA strand elongation, but also at the initiation of plus strand DNA synthesis as demonstrated for the N348I mutation. 2011 Antiviral research Abstract HIV N348I 182 187 21896288 HIV-1 reverse transcriptase connection subdomain mutations involved in resistance to approved non-nucleoside inhibitors. Studies on the effects of N348I and A376S on NNRTI resistance indicate that these changes could affect inhibitor binding by altering the interaction between RT subunits or between the RT and the template-primer. 2011 Antiviral research Abstract HIV A376S;N348I 36;26 41;31 NNRTI;RT;RT 45;157;184 50;159;186 21896904 TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. In vitro resistance selection (IVRS) experiments with WT virus and TMC310911 selected for mutations R41G or R41E, but selection of resistant virus required a longer time than IVRS performed with WT virus and DRV. 2011 Antimicrobial agents and chemotherapy Abstract HIV R41E;R41G 108;100 112;104 21896904 TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. IVRS performed with r13025 in the presence of DRV required less time and resulted in more PI resistance-associated mutations (V32I, I50V, G73S, L76V, and V82I; FC in DRV EC(50) = 258). 2011 Antimicrobial agents and chemotherapy Abstract HIV G73S;I50V;L76V;V32I;V82I 138;132;144;126;154 142;136;148;130;158 PI 90 92 21896904 TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. IVRS performed with r13025, a multiple-PI-resistant recombinant clinical isolate, and TMC310911 selected for mutations L10F, I47V, and L90M (FC in TMC310911 EC(50) = 16). 2011 Antimicrobial agents and chemotherapy Abstract HIV I47V;L10F;L90M 125;119;135 129;123;139 PI 39 41 21900719 Next-generation sequencing of dried blood spot specimens: a novel approach to HIV drug-resistance surveillance. An exception was an M184I mutation only detected with TPP of DBS at a frequency of 20.4%. 2011 Antiviral therapy Abstract HIV M184I 20 25 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. 147 ARV-naive subjects were sequenced to 0.4% levels; 8.8% (13/147) had K65R low-level variants identified: 2.2% (2/92) in subtype B, 35.7% (10/28) in subtype C (P<0.001 for B versus C) and 3.7% (1/27) in non-B/C subtypes. 2011 Antiviral therapy Abstract HIV K65R 72 76 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. BACKGROUND: It has been reported that treatment-naive individuals infected with HIV-1 subtype C may be more likely to harbour viral variants possessing a K65R reverse transcriptase gene mutation. 2011 Antiviral therapy Abstract HIV K65R 154 158 RT 159 180 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. CONCLUSIONS: Low-level K65R variants were more frequently identified in subtype C. 2011 Antiviral therapy Abstract HIV K65R 23 27 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. K65R variants at >1% levels likely represent transmitted resistant variants. 2011 Antiviral therapy Abstract HIV K65R 0 4 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. RESULTS: A total of 411 treatment-naive individuals were evaluated by ultra-deep sequencing to 1% levels; 4 subjects (0.97%) had K65R variants at >=1% or had a very high mutation load. 2011 Antiviral therapy Abstract HIV K65R 129 133 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. The 13 ARV-naive subjects with K65R variants at <1% received tenofovir plus emtricitabine plus a ritonavir-boosted protease inhibitor (TDF+FTC+PI/r) and 5 subsequently experienced virological failure. 2011 Antiviral therapy Abstract HIV K65R 31 35 PR;PI 115;143 123;145 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. The clinical implication of low-level K65R variants below 1% in treatment-naive subjects who receive TDF+FTC+PI/r remains to be determined as the majority are very low-level and did not increase after antiretroviral exposure. 2011 Antiviral therapy Abstract HIV K65R 38 42 PI 109 111 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. The objectives of this study were to determine the prevalence of low-level K65R variants within different HIV-1 subtypes and to assess the effects of antiretroviral exposure on K65R variant levels. 2011 Antiviral therapy Abstract HIV K65R;K65R 75;177 79;181 21900725 Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R and the effect of antiretroviral drug exposure on variant levels. There was no enhancement in K65R levels by percentage or mutational load compared to pre-therapy levels. 2011 Antiviral therapy Abstract HIV K65R 28 32 21900727 Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal. At M18 after RAL stop, integrase genotypic pattern evolved to T97A/Y143G. 2011 Antiviral therapy Abstract HIV T97A;Y143G 62;67 66;72 IN 23 32 21900727 Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal. In patient 1, the G140S/Q148R double-mutant was still detected at month (M)7 and at M11 after stopping RAL, but was no longer detected at M15. 2011 Antiviral therapy Abstract HIV G140S;Q148R 18;24 23;29 21900727 Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal. In patient 3, RAL-resistant virus with T97A/N155H mutations were still present 1 month after stopping RAL, and were no longer detected at M14. 2011 Antiviral therapy Abstract HIV N155H;T97A 44;39 49;43 21900727 Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal. Regarding patient 2, the double-mutant E92Q/N155H was still present at M2 and M8 after stopping RAL, and was no longer detected at M12. 2011 Antiviral therapy Abstract HIV E92Q;N155H 39;44 43;49 21900727 Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal. Regarding patient 4, the mutant T97A/Y143C was still detected at M1 and M3 following RAL withdrawal. 2011 Antiviral therapy Abstract HIV T97A;Y143C 32;37 36;42 21900727 Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal. RESULTS: At the time of RAL withdrawal, virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H, T97A/N155H and T97A/Y143C. 2011 Antiviral therapy Abstract HIV E92Q;G140S;N155H;N155H;Q148R;T97A;T97A;Y143C 110;97;127;115;103;122;137;142 114;102;132;120;108;126;141;147 IN 66 75 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Depletion of Tnp3 results in a re-distribution of HIV-1 capsid proteins between nucleus and cytoplasm however HIV-1 bearing the N74D mutation in capsid, which is insensitive to Tnp3 depletion, does not show nucleocytoplasmic redistribution of capsid proteins. 2011 PLoS pathogens Abstract HIV N74D 128 132 Capsid;Capsid;Capsid 56;145;243 62;151;249 21902276 Resolution of discordant HIV-1 protease resistance rankings using molecular dynamics simulations. Mutations at only three positions ( L10I , A71IV, andL90M ) influenced the resistance level assigned to the sequence. 2011 Journal of chemical information and modeling Abstract HIV A71I;A71V;L10I 43;43;36 48;48;40 21902592 Genetic diversity and drug resistance profiles in HIV type 1- and HIV type 2-infected patients from Cape Verde Islands. M41L and K103N transmitted drug resistance mutations were found in 2 of 17 (12%) untreated patients. 2012 AIDS research and human retroviruses Abstract HIV K103N;M41L 9;0 14;4 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. 2011 Bioorganic & medicinal chemistry Abstract HIV V106A 149 154 RT;RT 119;155 122;157 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. 2011 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 125;131 130;136 RT 137 139 21904187 Dynamics of gag-pol minority viral populations in naive HIV-1-infected patients failing protease inhibitor regimen. Among them, we described in one patient, that the predominant population at virological failure harboured in p2/p7 and TFP/p6(pol)-specific genotypic profiles associated with duplication of the P(T)APP motif in p6(gag) and the I15V protease mutation on the same individual molecular clones. 2011 AIDS (London, England) Abstract HIV I15V 227 231 PR;Pol;Gag;Gag;Gag 232;126;214;123;211 240;129;217;125;213 21904187 Dynamics of gag-pol minority viral populations in naive HIV-1-infected patients failing protease inhibitor regimen. In one patient, a I15V-mutated variant increased from 13 to 100% between baseline and week 24. 2011 AIDS (London, England) Abstract HIV I15V 18 22 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. We demonstrated that XMRV RT mutants K103R and Q190M, which are equivalent to HIV-1 mutants that are resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the respective drugs, suggesting that XMRV can acquire resistance to these compounds through the decreased incorporation mechanism reported in HIV-1. 2012 Nucleic acids research Abstract HIV K65R;Q151M;K103R;Q190M 125;140;37;47 129;145;42;52 RT 26 28 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. Mutant alpha4 proteins harboring the K201E/I/N substitution had reduced binding of all ligands tested, including HIV-1 gp120 envelopes. 2011 PloS one Abstract HIV K201E;K201I;K201N 37;37;37 46;46;46 Env;gp120 125;119 134;124 21915859 Genotypic tropism of antiretroviral-treated patients with drug resistant HIV-1. An association between viral X4 tropism and the M41L (P = 0.04) resistance mutation and R5 tropism and the K103N (P = 0.07) resistance mutation were observed. 2011 Journal of medical virology Abstract HIV K103N;M41L 107;48 112;52 21919802 HIV Type 1 genetic diversity and naturally occurring polymorphisms in HIV type 1 Kenyan isolates: implications for integrase inhibitors. One sample from this study and five from previous Kenyan integrase sequences had mutations at T97A, which is associated with reduced susceptibility to raltegravir. 2012 AIDS research and human retroviruses Abstract HIV T97A 94 98 IN 57 66 21919803 Drug resistance mutations in HIV type 1 isolates from patients failing antiretroviral therapy in Morocco. The prevalence of nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations was 13%, with K103N present in 57% of samples from NNRTIs-exposed patients. 2012 AIDS research and human retroviruses Abstract HIV K103N 96 101 NNRTI;NNRTI;NNRTI 18;65;133 53;70;139 21919803 Drug resistance mutations in HIV type 1 isolates from patients failing antiretroviral therapy in Morocco. The prevalence of nucleoside transcriptase inhibitor (NRTI) mutations was 48%, M184V being largely predominant. 2012 AIDS research and human retroviruses Abstract HIV M184V 79 84 NRTI 54 58 21919803 Drug resistance mutations in HIV type 1 isolates from patients failing antiretroviral therapy in Morocco. The prevalence of protease inhibitor (PI) mutations was 22%, with major mutations V82A and M46I seen in 16% and 11% of viruses from PI-exposed individuals, respectively. 2012 AIDS research and human retroviruses Abstract HIV M46I;V82A 91;82 95;86 PR;PI;PI 18;38;132 26;40;134 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Of 25 viremic patients followed for a median of 8 months on a continued first-line regimen, 12 (48%) re-suppressed, six with K103N and three with M184V. 2011 Journal of AIDS & clinical research Abstract HIV K103N;M184V 125;146 130;151 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Viral re-suppression in the presence of K103N and M184V challenges assumptions about drug resistance. 2011 Journal of AIDS & clinical research Abstract HIV K103N;M184V 40;50 45;55 21930388 Novel diarylpyridinones, diarylpyridazinones and diarylphthalazinones as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). The most promising compounds in these series are three diarylpyridazinones 25a, 25l and 25n which demonstrated submicromolar activity against wild-type HIV-1 and moderate activity against the single mutant strain Ba-L V106A. 2011 Bioorganic & medicinal chemistry Abstract HIV V106A 218 223 21932031 1H, 15N, and 13C resonance assignments for a monomeric mutant of the HIV-1 capsid protein. In this study, we have utilized a CA protein with W184A and M185A mutations that abolish the dimerization of CA protein as well as its infectivity, but preserve most of the remaining properties of the wild type CA. 2012 Biomolecular NMR assignments Abstract HIV M185A;W184A 60;50 65;55 Capsid;Capsid;Capsid 34;109;211 36;111;213 21932031 1H, 15N, and 13C resonance assignments for a monomeric mutant of the HIV-1 capsid protein. We have determined the detailed solution structure of the monomeric W184A/M185A-CA protein using 3D-NMR spectroscopy. 2012 Biomolecular NMR assignments Abstract HIV M185A;W184A 74;68 79;73 Capsid 80 82 21933785 Molecular and epidemiological characterization of HIV-1 infection networks involving transmitted drug resistance mutations in Northern Greece. Phylogenetic analyses revealed three statistically robust transmission clusters involving drug-resistant strains, including one cluster of 12 patients, 10 of whom were infected with a strain carrying both T215 revertants and Y181C mutations. 2011 The Journal of antimicrobial chemotherapy Abstract HIV Y181C 225 230 21933786 The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype. For this patient, the phenotypic analysis showed that addition of only the G118R mutation conferred a high level of resistance to raltegravir (fold change = 25.5) and elvitegravir (fold change = 9.2). 2011 The Journal of antimicrobial chemotherapy Abstract HIV G118R 75 80 21936717 Drug resistance mutations in HIV pol sequences from Argentinean patients under antiretroviral treatment: subtype, gender, and age issues. The most common DRMs were L10I, I54V, L90M, V82A, A71V, L10V, M46I, M184V, M41L, T215Y, D67N, L210W, K70R, N348I, V118I, K103N, Y181C, G190A, K101E, V108I, L100I, V90I, K101Q, and A98G. 2012 AIDS research and human retroviruses Abstract HIV A71V;A98G;D67N;G190A;I54V;K101E;K101Q;K103N;K70R;L100I;L10I;L10V;L210W;L90M;M184V;M41L;M46I;N348I;T215Y;V108I;V118I;V82A;V90I;Y181C 50;180;88;135;32;142;169;121;101;156;26;56;94;38;68;75;62;107;81;149;114;44;163;128 54;184;92;140;36;147;174;126;105;161;30;60;99;42;73;79;66;112;86;154;119;48;167;133 21942692 Virological response and resistance profiles after 24 months of first-line antiretroviral treatment in adults living in Bangui, Central African Republic. Even after excluding the M184V mutation, all 76% of patients in virological failure displayed viruses harboring at least one major drug resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI), non-NRTI, or protease inhibitors. 2012 AIDS research and human retroviruses Abstract HIV M184V 25 30 NRTI;NNRTI;PR;NRTI 159;211;224;204 191;219;232;208 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Previously, removal of an N-linked glycan at residue 448 by an N to Q mutation (N448Q) has been found to enhance the in vitro antigenicity of neutralizing epitopes in the V3 loop. 2011 Vaccine Abstract HIV N448Q 80 85 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Similar results were achieved with a complex made with gp120 bearing an N448E mutation, confirming the importance of the N448-linked glycan in modulating gp120 immunogenicity. 2011 Vaccine Abstract HIV N448E 72 77 gp120;gp120 55;154 60;159 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Subsequently, the N448Q mutant was used to construct an immune complex vaccine with the anti-CD4 binding site monoclonal antibody (mAb) 654. 2011 Vaccine Abstract HIV N448Q 18 23 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. The N448Q mutant did not elicit higher titers of anti-gp120 serum Abs and failed to generate anti-V3 Abs. 2011 Vaccine Abstract HIV N448Q 4 9 gp120 54 59 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. The N448Q/654 complex stimulated comparably high levels of serum Abs to gp120 and V3 as the wild type complex. 2011 Vaccine Abstract HIV N448Q 4 9 gp120 72 77 21953939 Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine. A support vector regression model, based on matched genotypic/phenotypic data (n=850), showed that among 6365 analyzed mutations, K103N, Y181C and G190A have the first, third, and sixth greatest significance for nevirapine resistance, respectively. 2011 ChemMedChem Abstract HIV G190A;K103N;Y181C 147;130;137 152;135;142 21953939 Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine. For efavirenz resistance, K103N, G190, and L100I have the first, fourth, and eighth greatest significance, respectively, as determined in support vector regression model. 2011 ChemMedChem Abstract HIV K103N;L100I 26;43 31;48 21953939 Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine. In particular, for nevirapine and efavirenz, a single mutation K103N was associated with the most unfavorable energetic profile compared to the wild-type sequence. 2011 ChemMedChem Abstract HIV K103N 63 68 21953939 Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine. Mutations detected for nevirapine virological failure with a prevalence greater than 10% in the used patient set were: K103N, Y181C, G190A, and K101E. 2011 ChemMedChem Abstract HIV G190A;K101E;K103N;Y181C 133;144;119;126 138;149;124;131 21953939 Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine. The most common indicator of treatment failure for efavirenz was K103N mutation present in 56.7% of the patients where the drug failed, followed by V108I, L100I, and G190A. 2011 ChemMedChem Abstract HIV G190A;K103N;L100I;V108I 166;65;155;148 171;70;160;153 21953939 Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine. This is in line with recent clinical data reporting that diarylpyrimidine etravirine, a very potent third generation drug effective against a wide range of drug-resistant HIV-1 variants, shows increased affinity towards K103N/S mutants due to its high conformational flexibility. 2011 ChemMedChem Abstract HIV K103N;K103S 220;220 227;227 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. Four (7.4%) of these were nucleoside RT inhibitor mutations (D67G, D67E, T69D, and T215Y), and one (1.9%) was a PR inhibitor mutation (M46I). 2011 Journal of health, population, and nutrition Abstract HIV D67E;D67G;M46I;T215Y;T69D 67;61;135;83;73 71;65;139;88;77 PR;RT 112;37 114;39 21970343 HIV type 1 integrase polymorphisms in treatment-naive and treatment-experienced HIV type 1-infected patients in Thailand where HIV type 1 subtype A/E predominates. Comparing INI-RAMs between subtype A/E and B, the prevalence of V54I and V72I was higher in subtype B than subtype E, while V201I was found in all sequences of subtype A/E. 2012 AIDS research and human retroviruses Abstract HIV V201I;V54I;V72I 124;64;73 129;68;77 IN 10 13 21970343 HIV type 1 integrase polymorphisms in treatment-naive and treatment-experienced HIV type 1-infected patients in Thailand where HIV type 1 subtype A/E predominates. Major INI-RAM was not found in this study, but some minor INI-RAMs, such asV54I, L68I, L74M, T97A, and S230N, were found. 2012 AIDS research and human retroviruses Abstract HIV L68I;L74M;S230N;T97A 81;87;103;93 85;91;108;97 IN;IN 6;58 9;61 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Amino acid changes Q148R and N155H individually conferred resistance to raltegravir (14-fold and seven-fold, respectively), whereas the Y143C replacement had no statistically significant effect on raltegravir sensitivity. 2011 AIDS (London, England) Abstract HIV N155H;Q148R;Y143C 29;19;136 34;24;141 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. CONCLUSION: Our data support clinical studies of raltegravir for treating HIV-2 infection and show that the Q148R and N155H changes alone are sufficient for raltegravir resistance in HIV-2. 2011 AIDS (London, England) Abstract HIV N155H;Q148R 118;108 123;113 HIV infections 74 89 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. The combination of Q148R with N155H resulted in high-level raltegravir resistance (>1000-fold). 2011 AIDS (London, England) Abstract HIV N155H;Q148R 30;19 35;24 21972264 Reverse transcriptase genotypes in pediatric patients failing initial antiretroviral therapy in Gaborone, Botswana. Nonnucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were associated with notable resistance to either/both NVP and EFV (n = 40; 88.9%); K103N (n = 15; 33.3%); >=1 mutations associated with etravirine (ETR) failure (K101E, Y181C, and G190A; n =20; 44.4%); and >=2 notable NNRTI mutations (n = 12; 26.7%). 2012 Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. Abstract HIV G190A;K101E;K103N;Y181C 265;247;168;254 270;252;173;259 NNRTI;NNRTI 0;303 35;308 21972264 Reverse transcriptase genotypes in pediatric patients failing initial antiretroviral therapy in Gaborone, Botswana. Nucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were M184V (n = 41; 91.1%); thymidine analogue mutations (TAMs; n = 20; 44.4%); >1 TAM (n = 9; 20%); TAM-2 pathway (n = 10; 22.2%); TAM-1 pathway (n = 7; 15.6%); TAM-1 and TAM-2 pathways (n = 3; 6.7%); K65R (n = 2; 4.4%); Q151M (n = 1; 2.2%); and L74V (n = 0; 0%). 2012 Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. Abstract HIV K65R;L74V;M184V;Q151M 283;328;86;303 287;332;91;308 NRTI 0 32 21975076 Primary HIV-1 drug resistance in the C-terminal domains of viral reverse transcriptase among drug-naive patients from Southern Brazil. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B (p=0.038), while the inverse was observed for mutation Q547K (p<0.001). 2011 Journal of clinical virology Abstract HIV D488E;Q547K 49;170 54;175 21975076 Primary HIV-1 drug resistance in the C-terminal domains of viral reverse transcriptase among drug-naive patients from Southern Brazil. RESULTS: The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. 2011 Journal of clinical virology Abstract HIV A376S;T369I;T369V 82;37;37 87;44;44 NNRTI 31 36 21976643 The cargo-binding domain of transportin 3 is required for lentivirus nuclear import. Mutation of a single amino acid, A76V in the SIVmac239 capsid, rendered the virus TNPO3 independent and resistant to mCPSF6-358, a truncated splicing factor that prevents HIV-1 nuclear import. 2011 Journal of virology Abstract HIV A76V 33 37 Capsid 55 61 21976663 Role for the terminal clasp of HIV-1 gp41 glycoprotein in the initiation of membrane fusion. Because the biosynthesis of the prefusion gp120-gp41 complex did not appear to be affected by I535A/V539G, we infer that the hemifusion block is due to a specific effect on the trimer of hairpins conformation of gp41. 2011 The Journal of biological chemistry Abstract HIV I535A;V539G 94;100 99;105 gp120;gp41;gp41 42;48;212 47;52;216 21976663 Role for the terminal clasp of HIV-1 gp41 glycoprotein in the initiation of membrane fusion. Limited proteolysis indicated that the terminal clasp is destabilized by simultaneous I535A/V539G mutations within the polar segment and mutations within the MPER. 2011 The Journal of biological chemistry Abstract HIV I535A;V539G 86;92 91;97 21976663 Role for the terminal clasp of HIV-1 gp41 glycoprotein in the initiation of membrane fusion. The destabilizing effects of I535A/V539G correlated with defective cell-cell fusion, viral entry, and viral replication. 2011 The Journal of biological chemistry Abstract HIV I535A;V539G 29;35 34;40 21990611 Resistance-associated mutations in HIV-1 among patients failing first-line antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-mutations were detected in 63.6% of sequences, of which Y181C/I (47.6%), K103N (33.3%) and G190S (28.6%) are the most common. 2012 Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. Abstract HIV G190S;K103N;Y181C;Y181I 156;138;121;121 161;143;128;128 NNRTI;NNRTI 0;47 35;52 21990611 Resistance-associated mutations in HIV-1 among patients failing first-line antiretroviral therapy. Nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations were seen among all patients, with M184V and thymidine analogue mutations (TAM) being most frequently detected (75.6% and 72.7%, respectively). 2012 Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. Abstract HIV M184V 106 111 NRTI;NRTI 0;44 32;48 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. Addition of M184I, but not M184V, to E138K, further decreased susceptibility to RPV and maintained FTC resistance. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184I;M184V 37;12;27 42;17;32 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. BACKGROUND: The registrational phase III clinical trials of the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) rilpivirine (RPV) in combination with two nucleoside/nucleotide RT inhibitors (NRTIs) found a unique genotypic resistance pattern involving the NNRTI mutation E138K with the NRTI mutation M184I. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184I 282;311 287;316 NNRTI;NNRTI;NNRTI;NRTI;NRTI;RT;RT 64;116;267;202;297;101;187 99;121;272;207;301;103;189 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. CONCLUSIONS: The higher frequency of E138K and M184I among RPV + FTC/TDF virologic failures is due to reduced susceptibility of the single mutants to RPV and FTC and the enhanced resistance to RPV for the double mutant at the cost of decreased viral fitness. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184I 37;47 42;52 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. E138K + M184I was less fit than either E138K or M184I alone. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184I;M184I;E138K 39;8;48;0 44;13;53;5 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. M184V outcompeted M184I when compared directly and in the background of E138K. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184I;M184V 72;18;0 77;23;5 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. METHODS: HIV-1 with E138K and/or M184V or I mutations were constructed and phenotyped in MT-2 cells and the PhenoSense and Antivirogram assays. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184V 20;33 25;38 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. RESULTS: The E138K mutant showed low-level reduced susceptibility to RPV (2.4-fold), but full susceptibility to FTC and tenofovir (TFV). 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K 13 18 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. The E138K and M184V or I single and double mutants showed decreased replication fitness compared with wild type. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184V 4;14 9;19 21997204 The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness. Viruses with M184V or M184I showed high-level resistance to FTC and full susceptibility to RPV and TFV. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 22;13 27;18 22006924 The highly conserved glycan at asparagine 260 of HIV-1 gp120 is indispensable for viral entry. In addition, the mutant N260Q HIV-1 envelope expressed in 293T cells was unable to form syncytia in co-cultures with U87.CD4.CXCR4.CCR5 cells, due to the lower expression of envelope protein on the surface of the transfected 293T cells. 2011 The Journal of biological chemistry Abstract HIV N260Q 24 29 Env;Env 36;174 44;182 22006924 The highly conserved glycan at asparagine 260 of HIV-1 gp120 is indispensable for viral entry. We observed a significant lower CD4 binding in the case of the N260Q mutant gp120 virus strains, caused by a strikingly lower expression of gp120 and gp41 in the virus particle. 2011 The Journal of biological chemistry Abstract HIV N260Q 63 68 gp120;gp120;gp41 76;140;150 81;145;154 22012712 Detection of distinct human immunodeficiency virus type 1 circulating recombinant forms in northeast Brazil. The substitutions I54V (7.0%), M184V (14.0%), and K103N (10.5%) were the most frequent within each class of drugs. 2011 Journal of medical virology Abstract HIV I54V;K103N;M184V 18;50;31 22;55;36 22013063 Mutations of Gln64 in the HIV-1 gp41 N-terminal heptad repeat render viruses resistant to peptide HIV fusion inhibitors targeting the gp41 pocket. They were also sensitive to C52L, which contains the PBD, GBD, and LBD. 2012 Journal of virology Abstract HIV C52L 28 32 22013063 Mutations of Gln64 in the HIV-1 gp41 N-terminal heptad repeat render viruses resistant to peptide HIV fusion inhibitors targeting the gp41 pocket. To prove that the peptidic HIV-1 fusion inhibitors containing the pocket-binding domain (PBD) mainly target the hydrophobic pocket in the gp41 N-terminal heptad repeat (NHR), we constructed pseudoviruses by replacement of Q64 in the gp41 pocket region with Ala (Q64A) or Leu (Q64L). 2012 Journal of virology Abstract HIV Q64A;Q64L 262;276 266;280 gp41;gp41 138;233 142;237 22017513 Difluoromethylbenzoxazole pyrimidine thioether derivatives: a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The most promising compound 24 showed a significant EC(50) value close to 6.4 nM against HIV-1 IIIB, a moderate EC(50) value close to 54 muM against an NNRTI resistant double mutant (K103N + Y181C), but an excellent selectivity index >15477 (CC(50) > 100 muM). 2011 Journal of medicinal chemistry Abstract HIV K103N;Y181C 183;191 189;196 NNRTI 152 157 22024508 A structural frame for understanding the role of thymidine analogue resistance mutations in resistance to zidovudine and other nucleoside analogues. These mutations, known as thymidine analogue resistance mutations (TAMs) are M41L, D67N, K70R, L210W, T215F/Y and K219E/Q. 2011 Antiviral therapy Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 83;114;114;89;95;77;102;102 87;121;121;93;100;81;109;109 22024519 Identification and structural characterization of novel genetic elements in the HIV-1 V3 loop regulating coreceptor usage. Their presence determines a decreased affinity for CCR5 N terminus even stronger than that observed in the presence of the well-known mutation S11R (N5Y: -6.60 Kcal/mol; N7K: -5.40 Kcal/mol; A19V: -5.60 Kcal/mol; S11R: -6.70 Kcal/mol; WT: -6.90 Kcal/mol). 2011 Antiviral therapy Abstract HIV A19V;S11R;S11R 191;143;213 195;147;217 22024519 Identification and structural characterization of novel genetic elements in the HIV-1 V3 loop regulating coreceptor usage. This is the case for N5Y and N7K, absent in CCR5-using viruses and present in 4.5% and 6% of CXCR4-using viruses, respectively, and A19V, occurring in 2.6% of CCR5-using viruses and 22.0% of CXCR4-using viruses (P=10(-2) to 10(-7)). 2011 Antiviral therapy Abstract HIV A19V 132 136 22024527 Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens. No E138R/E138K mutations were detected. 2011 Antiviral therapy Abstract HIV E138K;E138R 3;3 8;8 22024527 Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). 2011 Antiviral therapy Abstract HIV G190A;K103N;Y181C 45;61;32 50;66;37 NNRTI 11 16 22024527 Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens. The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). 2011 Antiviral therapy Abstract HIV K101P;Y181I;Y181V 61;75;92 66;80;97 22027876 Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M. BACKGROUND: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 168 173 22027876 Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M. Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV F214L;I202V;K43E;R211K;S162C;S68G;T165I;V60I 86;72;40;79;58;52;65;46 91;77;44;84;63;56;70;50 22027876 Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV F214L;Q151M;V60I 32;85;42 37;90;46 22027876 Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M. METHODS: The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), >=2 thymidine analogue mutations (TAM) 1 (n = 400) or >=2 TAM 2 (n = 249). 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV Q151M 188 193 22027876 Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M. S68G, T165I, and I202V were associated with Q151M instead of TAM 2. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I202V;Q151M;T165I;S68G 17;44;6;0 22;49;11;4 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. However, changes at position 675 in conjunction with Thr to Ala at position 569 increased the neutralization sensitivity to all gp41 and gp120 MAbs and plasma, in some cases by more than 1000-fold. 2011 Virology Abstract HIV T569A 53 79 gp120;gp41 137;128 142;132 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Interestingly, the T569A change had a dramatic effect on b12 binding, but no effect on neutralization sensitivity. 2011 Virology Abstract HIV T569A 19 24 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Infectivity of P147L and S149A is rescued specifically by pseudotyping with vesicular stomatitis virus envelope glycoprotein. 2011 Virology Abstract HIV P147L;S149A 15;25 20;30 Env 103 111 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Three classes of mutants were identified: (i) S146A and T148A behave like wild type (WT); (ii) Y145A, I150A, and L151A are noninfectious, assemble unstable cores with aberrant morphology, and synthesize almost no viral DNA; and (iii) P147L and S149A display a poorly infectious, attenuated phenotype. 2011 Virology Abstract HIV I150A;L151A;P147L;S146A;S149A;T148A;Y145A 102;113;232;44;244;56;93 107;118;239;51;249;61;100 22037848 F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). 2012 Antimicrobial agents and chemotherapy Abstract HIV Y181C 119 124 22037848 F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM), which was in stark contrast to the extensively used NNRTIs nevirapine and efavirenz. 2012 Antimicrobial agents and chemotherapy Abstract HIV Y181C 172 177 NNRTI;NNRTI 53;278 58;284 22037848 F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis. Moreover, we induced F18-resistant viruses by in vitro serial passages and found that the mutation L100I appeared to be the dominant contributor to F18 resistance, further suggesting a binding motif different from that of nevirapine and efavirenz. 2012 Antimicrobial agents and chemotherapy Abstract HIV L100I 99 104 22037850 Molecular dynamics approaches estimate the binding energy of HIV-1 integrase inhibitors and correlate with in vitro activity. Four well-characterized compounds (raltegravir, elvitegravir, MK-0536, and dolutegravir) were used as a training set, and the data for their in vitro activity against the Y143R, N155H, and G140S/Q148H mutants were used in addition to the wild-type (WT) IN data. 2012 Antimicrobial agents and chemotherapy Abstract HIV G140S;N155H;Q148H;Y143R 189;178;195;171 194;183;200;176 IN 253 255 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. K103N was the predominant mutation in all groups and periods. 2011 PloS one Abstract HIV K103N 0 5 22047156 Phenotypic analysis of HIV-1 genotypic drug-resistant isolates from China, using a single-cycle system. Mutations E44A, T69D, and V118I influenced the pattern of resistance of TAMs. 2011 Molecular diagnosis & therapy Abstract HIV E44A;T69D;V118I 10;16;26 14;20;31 22047156 Phenotypic analysis of HIV-1 genotypic drug-resistant isolates from China, using a single-cycle system. The phenotype results showed that individual pseudoviruses with four thymidine analog mutations (TAMs).[M41L, T67N, L210W, and T215Y] in combination with various other mutations had different levels of resistance to nucleoside reverse transcriptase inhibitors (NRTIs). 2011 Molecular diagnosis & therapy Abstract HIV L210W;M41L;T215Y;T67N 116;104;127;110 121;108;132;114 NRTI;NRTI 216;261 248;266 22067663 Interpretation of genotypic resistance to predict darunavir/ritonavir failure in antiretroviral experienced patients. Four mutations (V32I, I50V, L76V, I84V) were predictive of failure, the hazard ratio progressively increased by detecting 1 (hazard ratio: 2.0, 95% confidence interval: 1.3 to 3.0), 2 (3.6, 2.0 to 6.6), or 3 of them (9.7, 2.8 to 33.5). 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I50V;I84V;L76V;V32I 22;34;28;16 26;38;32;20 22067667 Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. More rilpivirine VFs had treatment-emergent nucleoside/nucleotide reverse transcriptase inhibitor RAMs than efavirenz VFs [68% (42 of 62) versus 32% (9 of 28), respectively], most commonly M184I and M184V. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 189;199 194;204 RT 66 87 22067667 Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. The absolute number of VFs with treatment-emergent NNRTI resistance-associated mutations (RAMs) was higher for rilpivirine (most commonly E138K or K101E) than efavirenz (most commonly K103N), but relative proportions were similar [63% (39 of 62) vs. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;K101E;K103N 138;147;184 143;152;189 NNRTI 51 56 22067667 Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. The frequent emergence of E138K, especially in combination with M184I, in rilpivirine VFs is a unique finding of these trials. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K;M184I 26;64 31;69 22072391 The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals. Furthermore, chronic treatment of hSOD1(G93A) mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. 2012 Human molecular genetics Abstract HIV G93A 40 44 Tat 60 63 22072391 The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1(G93A) mouse model of ALS. 2012 Human molecular genetics Abstract HIV G93A 135 139 22072391 The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals. Since non-physiological formation of IP(3) can prompt IP(3) receptor (IP(3)R)-mediated Ca(2+) release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca(2+) signaling that occurs downstream of mGluR5 in hSOD1(G93A)-expressing astrocytes. 2012 Human molecular genetics Abstract HIV G93A 271 275 Capsid;Capsid 87;212 89;214 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. We further obtained direct evidence to suggest that a hyperstable mutant capsid, E45A, showed delayed capsid disassembly compared to the wild-type capsid. 2011 Structure (London, England Abstract HIV E45A 81 85 Capsid;Capsid;Capsid 73;102;147 79;108;153 22078905 Detection and quantification of the K103N mutation in HIV reverse transcriptase by pyrosequencing. Prolonged treatment of human immunodeficiency virus (HIV)-infected patients with nonnucleoside reverse transcriptase inhibitors (NNRTIs) might result in the selection of resistant mutants, the most frequent being the K103N mutation in reverse transcriptase. 2012 Diagnostic microbiology and infectious disease Abstract HIV K103N 217 222 NNRTI;RT;NNRTI 81;235;129 116;256;135 22078905 Detection and quantification of the K103N mutation in HIV reverse transcriptase by pyrosequencing. The method was tested with samples from 5 controls (not exposed to NNRTIs), 6 from patients exposed to NNRTIs and having a K103N mutant virus population detected by conventional sequencing, and 9 from patients previously exposed to NNRTIs that had a wild-type virus population by conventional sequencing. 2012 Diagnostic microbiology and infectious disease Abstract HIV K103N 123 128 NNRTI;NNRTI;NNRTI 67;103;232 73;109;238 22083488 Interplay between single resistance-associated mutations in the HIV-1 protease and viral infectivity, protease activity, and inhibitor sensitivity. Virions containing 50% of a D25A mutant protease were 3- to 5-fold more sensitive to protease inhibitors. 2012 Antimicrobial agents and chemotherapy Abstract HIV D25A 28 32 PR;PR 40;85 48;93 22093289 Emergence of an HIV-1 cluster harbouring the major protease L90M mutation among treatment-naive patients in Tel Aviv, Israel. CONCLUSION: There was an unexpectedly high rate of the major L90M PI resistance mutation in the MSM group. 2012 HIV medicine Abstract HIV L90M 61 65 PI 66 68 22093289 Emergence of an HIV-1 cluster harbouring the major protease L90M mutation among treatment-naive patients in Tel Aviv, Israel. Phylogenetic analysis showed a tight cluster comprising 13 of 14 viruses harbouring the L90M major PI resistance mutation, suggesting a single infection source. 2012 HIV medicine Abstract HIV L90M 88 92 PI 99 101 22095519 Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates. METHODS: Here, we studied the interaction of selected halo- and nitro-substituted IAS derivatives, with the RT enzyme carrying the single resistance mutations K103N and Y181I through steady-state kinetic experiments. 2011 Antiviral chemistry & chemotherapy Abstract HIV K103N;Y181I 159;169 164;174 RT 108 110 22095519 Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates. The presence of the K103N mutation, and to a lesser extent the Y181I, stabilized the drug interactions with the viral RT, when both its substrates were bound. 2011 Antiviral chemistry & chemotherapy Abstract HIV K103N;Y181I 20;63 25;68 RT 118 120 22095671 Multiple drugs and multiple targets: an analysis of the electrostatic determinants of binding between non-nucleoside HIV-1 reverse transcriptase inhibitors and variants of HIV-1 RT. Moreover, toward the L100I/K103N double mutant, RPVs charge distribution is quite far from optimal. 2012 Proteins Abstract HIV K103N;L100I 27;21 32;26 22104208 Mutations in the HIV-1 reverse transcriptase tryptophan repeat motif affect virion maturation and Gag-Pol packaging. However, all mutants except for W410A exhibited significant decreases in virus-associated RT, presumably a result of unstable RT mutant degradation. 2012 Virology Abstract HIV W410A 32 37 RT;RT 90;126 92;128 22104208 Mutations in the HIV-1 reverse transcriptase tryptophan repeat motif affect virion maturation and Gag-Pol packaging. Mutations W398A, W401A and W406A decreased the enhancement effect of efavirenz on PR-mediated Gag processing efficiency, which is in agreement with their destabilizing RT effects. 2012 Virology Abstract HIV W398A;W401A;W406A 10;17;27 15;22;32 Gag;PR;RT 94;82;168 97;84;170 22104208 Mutations in the HIV-1 reverse transcriptase tryptophan repeat motif affect virion maturation and Gag-Pol packaging. With the exception of W402A, we found none of the single substitution mutations exerted major impacts on virus assembly or processing. 2012 Virology Abstract HIV W402A 22 27 22104436 Modification of HIV-1 reverse transcriptase and integrase activity by gold(III) complexes in direct biochemical assays. RT inhibition was decreased in the presence of a reducing agent (10mM DTT) and against the M184V HIV-1 RT mutant, while none of the gold(III) complexes were effective inhibitors in cell-based antiviral assays (SI values <5.95). 2012 Bioorganic & medicinal chemistry Abstract HIV M184V 91 96 RT;RT 0;103 2;105 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. A representative inhibitor (5e) retained most of its inhibitory potency against the three major raltegravir-resistant IN mutant enzymes, G140S/Q148H, Y143R, and N155H. 2012 Chemical biology & drug design Abstract HIV G140S;N155H;Q148H;Y143R 137;161;143;150 142;166;148;155 IN 118 120 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Against the N155H mutation, 5e was approximately 10-fold less affected than raltegravir. 2012 Chemical biology & drug design Abstract HIV N155H 12 17 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. In antiviral assays employing viral vectors coding these IN mutants, compound 5e was approximately 200- and 20-fold less affected than raltegravir against the G140S/Q148H and Y143R mutations, respectively. 2012 Chemical biology & drug design Abstract HIV G140S;Q148H;Y143R 159;165;175 164;170;180 IN 57 59 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Thus, our new compounds represent a novel structural class that may be further developed to overcome resistance to raltegravir, particularly in the case of the G140S/Q148H mutations. 2012 Chemical biology & drug design Abstract HIV G140S;Q148H 160;166 165;171 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Our analysis identified mutations V82A, I54V, K20I and I62V, which were associated with reduced viral response and mutations I15V and V91S which determined lopinavir/r hypersensitivity. 2011 PloS one Abstract HIV I15V;I54V;I62V;K20I;V82A;V91S 125;40;55;46;34;134 129;44;59;50;38;138 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. M184V was more common with nevirapine (87%) than efavirenz (63%). 2011 PloS one Abstract HIV M184V 0 5 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. The K103N mutation was detected in 83% of patients on efavirenz vs. 28% on nevirapine, whereas Y181C was detected in 56% on nevirapine vs. 20% efavirenz. 2011 PloS one Abstract HIV Y181C;K103N 95;4 100;9 22138483 E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. E17A had no impact on the biochemical and functional properties of Vpr, and did not affect kinetics of replication of wild-type or TAMs-containing viruses. 2012 Antiviral research Abstract HIV E17A 0 4 Vpr 67 70 22138483 E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. E17A was associated with thymidine analog mutations (TAMs) in reverse transcriptase M41L, L210W and T215Y and with the use of didanosine in the patients' treatment histories. 2012 Antiviral research Abstract HIV L210W;M41L;T215Y;E17A 90;84;100;0 95;88;105;4 RT 62 83 22138483 E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. However, its association with TAMs and the use of didanosine was consistent with phenotypic susceptibility assays showing a significant 3-fold decrease in didanosine susceptibility of viruses harboring Vpr E17A combined with TAMs compared to viruses harboring TAMs alone. 2012 Antiviral research Abstract HIV E17A 206 210 Vpr 202 205 22138483 E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. RESULTS: E17A mutation located in the first alpha-helix of Vpr was more prevalent in HAART-treated individuals compared to untreated individuals. 2012 Antiviral research Abstract HIV E17A 9 13 Vpr 59 62 22138483 E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. Vpr E17A confers resistance to didanosine when associated with TAMs. 2012 Antiviral research Abstract HIV E17A 4 8 Vpr 0 3 22138483 E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations. Whether Vpr E17A facilitates excision of didanosine is still to be determined. 2012 Antiviral research Abstract HIV E17A 12 16 Vpr 8 11 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Here, the effects of two adjuvants, monophosphoryl lipid A (MPL) and Quil A, on eliciting b12-like responses when formulated with a new hyperglycosylated mutant, DeltaN2mCHO(Q105N), is presented. 2012 Vaccine Abstract HIV Q105N 174 179 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Our results show that although formulating mutant DeltaN2mCHO(Q105N) with Quil A promotes the elicitation of CD4bs-directed antibodies relative to wild-type gp120, tweaking of the immunization regimen is needed to yield robust, CD4bs-focused NAbs. 2012 Vaccine Abstract HIV Q105N 62 67 gp120 157 162 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Sera from DeltaN2mCHO(Q105N)_MPL immunized animals bound the homologous antigen DeltaN2mCHO(Q105N) with greater preference than sera from DeltaN2mCHO(Q105N)_QuilA immunized animals, demonstrating the modulation of antibody fine specificity by these two adjuvants. 2012 Vaccine Abstract HIV Q105N;Q105N;Q105N 22;92;150 27;97;155 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. We also found that sera from DeltaN2mCHO(Q105N)_QuilA immunized animals bound best to a resurfaced HIV gp120 core protein on which non-CD4bs epitopes are substituted with non-HIV residues, suggesting that these sera contain a relatively larger fraction of CD4bs-specific antibodies. 2012 Vaccine Abstract HIV Q105N 41 46 gp120 103 108 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Crosslinking of an R244C ASV IN derivative identified contacts at positions 11 and 12 on both strands of viral DNA. 2011 PloS one Abstract HIV R244C 19 24 IN 29 31 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. The most efficient disulfide crosslinking was observed for complexes of the ASV IN E157C and D64C derivatives with linear viral DNA substrate carrying a thiol-modified scissile phosphate. 2011 PloS one Abstract HIV D64C;E157C 93;83 97;88 IN 80 82 22145994 Characterization of protease resistance-associated mutations in HIV type 1 drug-naive patients following the increasing prevalence of the CRF02_AG strain in Morocco. These results support the importance of transmitted drug resistance mutations (M36I/L, H69K, and L89M) in the protease gene of HIV-1 CRF02_AG isolates. 2012 AIDS research and human retroviruses Abstract HIV H69K;L89M;M36I;M36L 87;97;79;79 91;101;85;85 PR 110 118 22145994 Characterization of protease resistance-associated mutations in HIV type 1 drug-naive patients following the increasing prevalence of the CRF02_AG strain in Morocco. When compared to the B subtype, patients with the CRF02_AG strain had a significantly higher prevalence of mutations associated with resistance to some antiprotease drugs, mainly tipranavir (TPV): H69K (97% vs. 5%; p<0.0001), L89M (95% vs. 1%; p<0.0001), and M36I/L (93% vs. 44%; p<0.0001). 2012 AIDS research and human retroviruses Abstract HIV M36I;M36L;L89M;H69K 259;259;226;197 265;265;230;201 22149307 Short communication: High prevalence of transmitted antiretroviral drug resistance among newly HIV type 1 diagnosed adults in Mombasa, Kenya. Resistance to nonnucleoside reverse transcriptase inhibitors (K103N) occurred in five participants, yielding a TDR prevalence of 7.4% (95% confidence interval 2.4-16.3%). 2012 AIDS research and human retroviruses Abstract HIV K103N 62 67 NNRTI 14 49 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. However, the K(d) values of WT and A114C RT remained equivalent with an acyclic dNTP substrate. 2012 Virology Abstract HIV A114C 35 40 RT 41 43 22155917 Surveillance of antiretroviral drug resistance mutations in untreated young children living in the Central African Republic. DRM to non-nucleoside reverse transcriptase inhibitors were found in 5 samples (11.6% [95% CI, 2.0-21.2]) involving K103N, Y181C and G190A mutations. 2011 Antiviral therapy Abstract HIV G190A;K103N;Y181C 133;116;123 138;121;128 NNRTI 7 43 22155917 Surveillance of antiretroviral drug resistance mutations in untreated young children living in the Central African Republic. DRMs to nucleoside reverse transcriptase inhibitors was found in 1 sample (2.3% [95% CI 0.0-6.8]), with the K219Q mutation. 2011 Antiviral therapy Abstract HIV K219Q 108 113 NRTI 8 40 22156517 A highly conserved residue in the C-terminal helix of HIV-1 matrix is required for envelope incorporation into virus particles. We find that E99V mutant viruses are defective for fusion with cell membranes and thus are noninfectious. 2012 Journal of virology Abstract HIV E99V 13 17 22156517 A highly conserved residue in the C-terminal helix of HIV-1 matrix is required for envelope incorporation into virus particles. We identify a compensatory substitution in MA residue 84 and show that it can reverse the E99V-associated defects. 2012 Journal of virology Abstract HIV E99V 90 94 Matrix 43 45 22156517 A highly conserved residue in the C-terminal helix of HIV-1 matrix is required for envelope incorporation into virus particles. We show that E99V mutant particles of HIV-1 strains LAI and NL4.3 lack wild-type levels of Env proteins. 2012 Journal of virology Abstract HIV E99V 13 17 Env 91 94 22158948 Transmission of HIV-1 drug resistance in Benin could jeopardise future treatment options. Four patients had non-nucleoside reverse transcriptase inhibitor resistance (K103N, G190A). 2012 Sexually transmitted infections Abstract HIV G190A;K103N 84;77 89;82 NNRTI 18 54 22158948 Transmission of HIV-1 drug resistance in Benin could jeopardise future treatment options. One patient exhibited protease inhibitors resistance mutation, F53Y. 2012 Sexually transmitted infections Abstract HIV F53Y 63 67 PR 22 30 22159483 Differential expression of human beta defensins in placenta and detection of allelic variants in the DEFB1 gene from HIV-1 positive mothers. Additionally, simultaneous presence of the A692G A/G and A1836G G/G genotypes was associated with high expression of HBD-1 in all populations and the A692G variant in babies born to seropositive mothers was in Hardy-Weinberg disequilibrium. 2011 Biomedica Abstract HIV A1836G;A692G;A692G 57;43;150 63;48;155 22159483 Differential expression of human beta defensins in placenta and detection of allelic variants in the DEFB1 gene from HIV-1 positive mothers. HBD-1, -2 and -3 transcripts were quantified by real time RT-PCR, and A692G/G1654A/A1836G variants in the DEFB1 gene were evaluated by sequencing. 2011 Biomedica Abstract HIV A1836G;A692G;G1654A 83;70;76 89;75;82 RT 58 60 22160938 Emerging trends of drug-resistant HIV-1 among drug-treated patients in former blood donors in Hubei, China: a three-year surveillance from 2004 to 2006. Genotypic drug resistance analysis showed significant increases in percentages of patients carrying HIV-1 strains with M41L, T215Y/F, D67N, K103N, G190A/S, Y181C/F or L210W mutations. 2011 Virologica Sinica Abstract HIV D67N;G190A;G190S;K103N;L210W;M41L;T215F;T215Y;Y181C;Y181F 134;147;147;140;167;119;125;125;156;156 138;154;154;145;172;123;132;132;163;163 22166519 Allele-specific real-time PCR testing for minor HIV-1 drug resistance mutations: assay preparation and application to reveal dynamic of mutations in vivo. METHODS: We developed the allele-specific PCR assay, using the most common drug resistance mutations in Chinese AIDS patients, K103N, M184V/I, T215F/Y as a model system. 2010 Chinese medical journal Abstract HIV K103N;M184I;M184V;T215F;T215Y 127;134;134;143;143 132;141;141;150;150 AIDS 112 116 22166519 Allele-specific real-time PCR testing for minor HIV-1 drug resistance mutations: assay preparation and application to reveal dynamic of mutations in vivo. RESULTS: The sensitivities of ASPCR assay were 0.04% for K103N, 0.30% for M184I, 0.40% for M184V, 0.03% for T215F and 0.02% for T215Y. 2010 Chinese medical journal Abstract HIV K103N;M184I;M184V;T215F;T215Y 57;74;91;108;128 62;79;96;113;133 22166519 Allele-specific real-time PCR testing for minor HIV-1 drug resistance mutations: assay preparation and application to reveal dynamic of mutations in vivo. The mutation of T215Y emerged 1 to 1.5 years after starting treatment and then increased rapidly. 2010 Chinese medical journal Abstract HIV T215Y 16 21 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. HIV-1 cyclophilin-binding mutants CA G89V and P90A favored integration in genomic regions with a higher density of transcription units and associated features than wild type virus. 2011 PLoS pathogens Abstract HIV G89V;P90A 37;46 41;50 Capsid 34 36 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. In contrast, HIV-1 CA alterations in another patch on the capsid surface that render the virus less sensitive to Nup358 or TRN-SR2 depletion (CA N74D, N57A) resulted in integration in genomic regions sparse in transcription units. 2011 PLoS pathogens Abstract HIV N57A;N74D 151;145 155;149 Capsid;Capsid;Capsid 58;19;142 64;21;144 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Among them, IN W131A and IN Q168L, that were previously identified to be deficient for LEDGF/p75 interaction, were also partially impaired for TNPO3 binding. 2011 Retrovirology Abstract HIV Q168L;W131A 28;15 33;20 IN;IN 12;25 14;27 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. A significantly higher total number of mutations were encountered in severely immunosuppressed patients, who presented also major mutations in the protease gene (V82A, I54V, G48V) and the major M184V mutation associated with type 2 thymidine analogs mutations in reverstranscriptase gene.CONCLUSION: A good immune status seems to be associated with a low range of mutations, indicating the impact of immune restoration or preservation on the therapeutic success rate. 2011 Romanian biotechnological letters Abstract HIV G48V;I54V;M184V;V82A 174;168;194;162 178;172;199;166 PR 147 155 22188777 Genetic and structural analysis of HIV-1 Rev responsive element related to V38A and T18A enfuvirtide resistance mutations. METHODS: Collecting 476 and 135 HIV-1 B-subtype gp41 sequences from enfuvirtide-naive and enfuvirtide-treated patients, respectively, two mutations previously found associated with enfuvirtide treatment, T18A and V38A, were analyzed. 2012 Intervirology Abstract HIV T18A;V38A 204;213 208;217 gp41 48 52 22188777 Genetic and structural analysis of HIV-1 Rev responsive element related to V38A and T18A enfuvirtide resistance mutations. We previously found the co-presence of V38A+T18A resistance mutations in patients failing enfuvirtide. 2012 Intervirology Abstract HIV T18A;V38A 44;39 48;43 22188777 Genetic and structural analysis of HIV-1 Rev responsive element related to V38A and T18A enfuvirtide resistance mutations. While a structural RRE impairment in the presence of V38A alone was found, a restoration of the original RRE structure occurred in co-presence of V38A+T18A. 2012 Intervirology Abstract HIV T18A;V38A;V38A 151;53;146 155;57;150 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. The K103N mutation is normally associated with resistance to NNRTIs. 2012 Archives of virology Abstract HIV K103N 4 9 NNRTI 61 67 22192629 Highly conserved HIV-1 gp120 glycans proximal to CD4-binding region affect viral infectivity and neutralizing antibody induction. We found that mutants N156-T158A, N197-S199A, N262-S264A and N410-T412A conferred decreased infectivity and enhanced sensitivity to a series of antibodies and entry inhibitors. 2012 Virology Abstract HIV S199A;S264A;T158A;T412A 39;51;27;66 44;56;32;71 22192629 Highly conserved HIV-1 gp120 glycans proximal to CD4-binding region affect viral infectivity and neutralizing antibody induction. When mice were immunized with the DNA of wild-type or mutated gp160, gp140 or gp120; N156-T158A, N262-S264A and N410-T412A were more effective in inducing neutralizing activity against wild-type MWS2 as well as heterologous IIIB and CH811 Envs. 2012 Virology Abstract HIV S264A;T158A;T412A 102;90;117 107;95;122 gp120;gp140;gp160;Env 78;69;62;239 83;74;67;243 22197635 In vitro resistance selections using elvitegravir, raltegravir, and two metabolites of elvitegravir M1 and M4. Additional resistance selection experiments using elvitegravir led to the development of previously reported integrase inhibitor resistance mutations (T66I, F121Y, and S153Y) as well as a novel R263K integrase mutation. 2012 Antiviral research Abstract HIV F121Y;R263K;S153Y;T66I 157;194;168;151 162;199;173;155 IN;IN 109;200 118;209 22197635 In vitro resistance selections using elvitegravir, raltegravir, and two metabolites of elvitegravir M1 and M4. Resistance selection experiments using metabolites M1 and M4 led to the development of the previously reported elvitegravir integrase resistance mutations H51Y, T66A, E92G, and S147G, as well as a novel S153F substitution. 2012 Antiviral research Abstract HIV E92G;H51Y;S147G;S153F;T66A 167;155;177;203;161 171;159;182;208;165 IN 124 133 22200907 Control of M184V HIV-1 mutants by CD8 T-cell responses. Focusing on the M184V mutation, A*02:01-YQYVDDLYV and A*02:01-VIYQYVDDLYV were identified as optimal epitopes for the majority of study subjects. 2012 Medical microbiology and immunology Abstract HIV M184V 16 21 22200907 Control of M184V HIV-1 mutants by CD8 T-cell responses. In case of a failing lamivudine/emtricitabine containing regimen, individuals with a CD8 T-cell response toward M184V had a significant lower viral load than those without a CD8 response (p = 0.005). 2012 Medical microbiology and immunology Abstract HIV M184V 112 117 22200907 Control of M184V HIV-1 mutants by CD8 T-cell responses. Our data suggest that control of M184V mutant virus by CD8 T-cell responses is possible in vitro and in vivo. 2012 Medical microbiology and immunology Abstract HIV M184V 33 38 22200907 Control of M184V HIV-1 mutants by CD8 T-cell responses. Viral replication inhibition assays were performed using M184V mutant virus and CD8 T cell lines. 2012 Medical microbiology and immunology Abstract HIV M184V 57 62 22200907 Control of M184V HIV-1 mutants by CD8 T-cell responses. Viral replication of M184V HIV mutants was inhibited by CD8 T cell lines in vitro. 2012 Medical microbiology and immunology Abstract HIV M184V 21 26 22200908 Mutational patterns in the frameshift-regulating site of HIV-1 selected by protease inhibitors. Additionally, two Gag non-cleavage site mutations (S440F, H441P) were observed more often in HIV-1 isolates carrying protease resistance mutations. 2012 Medical microbiology and immunology Abstract HIV H441P;S440F 58;51 63;56 PR;Gag 117;18 125;21 22200908 Mutational patterns in the frameshift-regulating site of HIV-1 selected by protease inhibitors. HIV-1 Gag cleavage site mutations (G435E, K436N, I437V, L449F/V) especially correlated with protease inhibitor resistance mutations, but also Pol cleavage site mutations (D05G, D05S) could be assigned to specific protease resistance profiles. 2012 Medical microbiology and immunology Abstract HIV D05G;D05S;G435E;I437V;K436N;L449F;L449V 171;177;35;49;42;56;56 175;181;40;54;47;63;63 PR;PR;Pol;Gag 92;213;142;6 100;221;145;9 22205735 Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. Biochemical cell-free assays performed with purified IN enzyme containing R263K confirmed the absence of major resistance against DTG and showed a slight decrease in 3' processing and strand transfer activities compared to the wild type. 2012 Journal of virology Abstract HIV R263K 74 79 IN 53 55 22205735 Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. Further analysis by site-directed mutagenesis showed that R263K does confer low-level resistance to DTG and decreased integration in cell culture without altering reverse transcription. 2012 Journal of virology Abstract HIV R263K 58 63 RT 163 184 22205735 Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. Structural modeling suggested and in vitro IN-DNA binding assays show that the R263K mutation affects IN-DNA interactions. 2012 Journal of virology Abstract HIV R263K 79 84 IN;IN 43;102 45;104 22205735 Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. Therefore, we performed in vitro selection experiments with DTG using viruses of subtypes B, C, and A/G and showed that the most common mutation to emerge was R263K. 2012 Journal of virology Abstract HIV R263K 159 164 22209291 Prevalence of TMC278 (rilpivirine) associated mutations in the Frankfurt Resistance Database. OBJECTIVE: Objective of our investigation was to determine the prevalence of mutations E138K, Y181I/V, and K101E/P before the approval of rilpivirine. 2012 Journal of clinical virology Abstract HIV E138K;K101E;K101P;Y181I;Y181V 87;107;107;94;94 92;114;114;101;101 22209291 Prevalence of TMC278 (rilpivirine) associated mutations in the Frankfurt Resistance Database. RESULTS: The E138K, Y181I/V, and the K101E mutations were found in 0.4%, 0.9%, and 2.4% of the patients, respectively. 2012 Journal of clinical virology Abstract HIV E138K;K101E;Y181I;Y181V 13;37;20;20 18;42;27;27 22211659 Does GSS still maintain relevance on HAART outcome after the introduction of newest active antiretroviral drugs? 48 weeks results. About 60% of tests reported L10FIRVC, M36ILV, M46IL, I54VLAMTS, V82AFTSLI, and L90M mutations in the protease region. 2011 Current HIV research Abstract HIV I54A;I54L;I54M;I54S;I54T;I54V;L10C;L10F;L10I;L10R;L10V;L90M;M36I;M36L;M36V;M46I;M46L;V82A;V82F;V82I;V82L;V82S;V82T 53;53;53;53;53;53;28;28;28;28;28;79;38;38;38;46;46;64;64;64;64;64;64 62;62;62;62;62;62;36;36;36;36;36;83;44;44;44;51;51;73;73;73;73;73;73 PR 101 109 22211659 Does GSS still maintain relevance on HAART outcome after the introduction of newest active antiretroviral drugs? 48 weeks results. Data also showed a > 60% recurrence of specific mutations for NRTI: M41L, M184IV, L210W, T215FY, K219EQ and 75% for D67N. 2011 Current HIV research Abstract HIV D67N;K219E;K219Q;L210W;M184I;M184V;M41L;T215F;T215Y 116;97;97;82;74;74;68;89;89 120;103;103;87;80;80;72;95;95 NRTI 62 66 22211659 Does GSS still maintain relevance on HAART outcome after the introduction of newest active antiretroviral drugs? 48 weeks results. K103N and Y181CIV mutations for NNRTI persisted in 35% of cases and their prevalence incresed in parallel with the number of GRTs. 2011 Current HIV research Abstract HIV Y181C;Y181I;Y181V;K103N 10;10;10;0 17;17;17;5 NNRTI 32 37 22214532 Short communication: analysis of the integrase gene from HIV type 1-positive patients living in a rural area of West Cameroon. Interestingly, two patients infected with the CRF02_AG subtype had the resistance mutations N155H and E157Q/E and 12% of African samples had an amino acid substitution at position 143. 2012 AIDS research and human retroviruses Abstract HIV E157E;E157Q;N155H 102;102;92 109;109;97 22236055 Drug resistance mutations of HIV type 1 non-B viruses to integrase inhibitors in treatment-naive patients from sub-saharan countries and discordant interpretations. All but one (E157Q) were considered as accessory resistant mutation by the algorithms. 2012 AIDS research and human retroviruses Abstract HIV E157Q 13 18 22236055 Drug resistance mutations of HIV type 1 non-B viruses to integrase inhibitors in treatment-naive patients from sub-saharan countries and discordant interpretations. E157Q identified in 5% of patients tested (5/97) was selected by the ANRS algorithm as a primary mutation, which alone can confer resistance to raltegravir. 2012 AIDS research and human retroviruses Abstract HIV E157Q 0 5 22236055 Drug resistance mutations of HIV type 1 non-B viruses to integrase inhibitors in treatment-naive patients from sub-saharan countries and discordant interpretations. Using currently available interpretation algorithms (ANRS, HIVdb, and Rega), we identified the presence of mutations at nine resistance-associated positions including L74M (3.1%), T97A (9.3%), K156N (2.1%), E157Q (5.2%), G163K (1.0%), T206S (48.5%), S230N (1.0%), D232N (1.0%), and R236K (1.0%). 2012 AIDS research and human retroviruses Abstract HIV D232N;E157Q;G163K;K156N;L74M;R236K;S230N;T206S;T97A 264;207;221;193;167;282;250;235;180 269;212;226;198;171;287;255;240;184 22237471 Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. 2012 Infection Abstract HIV I50V;I54L;T74P;V11I;V32I 85;64;76;70;58 89;68;80;74;62 22237471 Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis. DISCUSSION: The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. 2012 Infection Abstract HIV I84V;V32I 132;123 136;127 22238126 Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors. Furthermore, we analyzed the PR1 mutant (PR(1M) ) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR2. 2012 Protein science Abstract HIV I47V;V32I;V82I 75;69;85 79;73;89 PR;PR;PR 131;29;41 134;32;43 22238317 Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. Constructs encoding the T186S mutation in combination with other putative compensatory mutations were attenuated or defective. 2012 Journal of virology Abstract HIV T186S 24 29 22238317 Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. Engineering of the T186S mutation alone into all patient-derived subtype C sequences failed to yield replication-competent viruses, while in the subtype B sequence, the T186S mutation resulted in impaired replication capacity. 2012 Journal of virology Abstract HIV T186S;T186S 19;169 24;174 22238317 Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. In addition, we investigated potential compensatory effects of various polymorphisms, including other HLA-B*81-associated mutations that significantly covary with the T186S mutation. 2012 Journal of virology Abstract HIV T186S 167 172 22238317 Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. Only the T186S mutation in combination with the T190I mutation yielded replication-competent viruses for all virus backbones tested; however, these constructs replicated slower than the wild type, suggesting that only partial compensation is mediated by the T190I mutation. 2012 Journal of virology Abstract HIV T186S;T190I;T190I 9;48;258 14;53;263 22238317 Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. These results suggest that the T186S mutation is deleterious to HIV-1 subtype C replication and likely requires complex compensatory pathways, which may contribute to the clinical benefit associated with HLA-B*81. 2012 Journal of virology Abstract HIV T186S 31 36 22238317 Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. We previously showed that the protective allele HLA-B*81 and the HLA-B*81-selected Gag T186S mutation are strongly associated with a lower viral replication capacity of recombinant viruses encoding Gag-protease derived from individuals chronically infected with HIV-1 subtype C. 2012 Journal of virology Abstract HIV T186S 87 92 PR;Gag;Gag 202;83;198 210;86;201 22238474 Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing. At UDPS, not all resistant variants appearing early during treatment evolved as major populations during failure; only specific resistance pathways (Y143R-Q148H/R-N155H) associated with an increased rate of fitness and phenotypic resistance were selected. 2012 The Journal of infectious diseases Abstract HIV N155H;Q148H;Q148R;Y143R 163;155;155;149 168;162;162;154 22238474 Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing. RESULTS: At baseline, primary resistance mutations were not detected by both population and UDPS genotypic assays; few secondary mutations (T97A-V151I-G163R) were rarely detected and did not show any statistically association either with virologic response at 24-weeks or with the development of resistant variants at failure. 2012 The Journal of infectious diseases Abstract HIV G163R;T97A;V151I 151;140;145 156;144;150 22239233 Replication-independent expression of anti-apoptosis marker genes in human peripheral blood mononuclear cells infected with the wild-type HIV-1 and reverse transcriptase variants. Compared with WT, a significant decrease in RCs of viruses: K65R (RC=0.39+-0.02; p<=0.0001), M184V (RC=0.72+-0.04; p<=0.0001), PSD5.1 (RC=0.32+-0.04; p<=0.0001), and PSD5.2 (RC=0.90+-0.04; p=0.002) was observed on day 10. 2012 Viral immunology Abstract HIV K65R;M184V 60;93 64;98 22239233 Replication-independent expression of anti-apoptosis marker genes in human peripheral blood mononuclear cells infected with the wild-type HIV-1 and reverse transcriptase variants. Point mutant K65R showed a 1.5- to 4-fold upregulation of six AAMGs on day 7. 2012 Viral immunology Abstract HIV K65R 13 17 22239233 Replication-independent expression of anti-apoptosis marker genes in human peripheral blood mononuclear cells infected with the wild-type HIV-1 and reverse transcriptase variants. The viruses containing patient-derived MDR RT without the K65R mutation (PSD5.2) replicated efficiently in comparison to the viruses with MDR RT containing the K65R mutation (PSD5.1), or the single mutations K65R and M184V. 2012 Viral immunology Abstract HIV K65R;K65R;K65R;M184V 58;160;208;217 62;164;212;222 RT;RT 43;142 45;144 22239233 Replication-independent expression of anti-apoptosis marker genes in human peripheral blood mononuclear cells infected with the wild-type HIV-1 and reverse transcriptase variants. Viruses with the M184V mutation showed upregulation of only one gene (BAG1). 2012 Viral immunology Abstract HIV M184V 17 22 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. As for the other previous studies, the present results also show that the single mutant I50V decreases the binding affinity of I50V-HIV-pr to TMC, resulting in a drug resistance; whereas the double mutant I50L/A71V increases the binding affinity, and as a result of the stronger binding, the I50L/A71V may be well adapted by the TMC114. 2012 The journal of physical chemistry. B Abstract HIV A71V;A71V;I50L;I50L;I50V;I50V 210;297;292;205;88;127 214;301;296;209;92;131 PR 136 138 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Besides the direct effects from the residues Leu50 and Leu50', the residue Gly49' increases the binding affinity of I50L/A71V-HIV-pr to the inhibitor by -0.74 kcal/mol, to which the electrostatic interaction of Leu50's backbone contributes by -1.23 kcal/mol. 2012 The journal of physical chemistry. B Abstract HIV A71V;I50L 121;116 125;120 PR 130 132 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For both the apo and complexed HIV-pr, many intriguing effects due to double mutant, I50L/A71V, are observed. 2012 The journal of physical chemistry. B Abstract HIV A71V;I50L 90;85 94;89 PR 35 37 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For example, the flap-flap distance and the distance from the active site to the flap residues in the apo I50L/A71V-HIV-pr are smaller than those of WT- and I50V-HIV-pr, probably making the active site smaller in volume and closer movement of flaps. 2012 The journal of physical chemistry. B Abstract HIV A71V;I50L;I50V 111;106;157 115;110;161 PR;PR 120;166 122;168 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For the complexed HIV-pr with TMC114, the double mutant I50L/A71V shows a less curling of the flap tips and less flexibility than WT and the single mutant I50V. 2012 The journal of physical chemistry. B Abstract HIV A71V;I50L;I50V 61;56;155 65;60;159 PR 22 24 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In the present work, the binding of inhibitor TMC114 (darunavir) to wild-type (WT), single (I50V) as well as double (I50L/A71V) mutant HIV-proteases (HIV-pr) was investigated with all-atom molecular dynamics (MD) simulations as well as molecular mechanic-Poisson-Boltzmann surface area (MM-PBSA) calculation. 2012 The journal of physical chemistry. B Abstract HIV I50L;A71V;I50V 117;122;92 121;126;96 PR;PR 139;154 148;156 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The energy decomposition analysis suggests that the increase of the binding for the double mutant I50L/A71V-HIV-pr can be mainly attributed to the increase in electrostatic energy by -5.52 kacl/mol and van der Waals by -0.42 kcal/mol, which are canceled out in part by the increase of polar solvation energy of 1.99 kcal/mol. 2012 The journal of physical chemistry. B Abstract HIV A71V;I50L 103;98 107;102 PR 112 114 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The I50L/A71V mutant directly increases the binding affinity by approximately -0.88 (Ile50 to Leu50) and -0.90 (Ile50' to Leu50') kcal/mol, accounting 45% for the total gain of the binding affinity. 2012 The journal of physical chemistry. B Abstract HIV A71V;I50L;I50L 9;4;85 13;8;99 22251009 Primary drug resistance in South Africa: data from 10 years of surveys. The most common mutations were associated with NNRTI resistance, K103N, followed by Y181C and Y188C/L. 2012 AIDS research and human retroviruses Abstract HIV K103N;Y181C;Y188C;Y188L 65;84;94;94 70;89;101;101 NNRTI 47 52 22251084 The analysis of near full-length genome sequences of HIV type 1 subtype A viruses from Russia supports the monophyly of major intrasubtype clusters. Samples were selected based on phylogenetic clustering in protease-reverse transcriptase in two of the major A(FSU) clusters, V77I(PR) (n=6), widely circulating in Russia and other FSU countries, and A(SP1) (n=4), predominant in St. 2012 AIDS research and human retroviruses Abstract HIV V77I 126 130 RT;PR;SP1;PR 67;58;202;131 88;66;205;133 22251084 The analysis of near full-length genome sequences of HIV type 1 subtype A viruses from Russia supports the monophyly of major intrasubtype clusters. The phylogenetic analysis shows that the V77I(PR) genomes group in a monophyletic cluster together with 10 previously obtained A(FSU) genome sequences from Uzbekistan, Kazakhstan, Russia, and Cyprus, all bearing the V77I substitution in protease. 2012 AIDS research and human retroviruses Abstract HIV V77I;V77I 41;216 45;220 PR;PR 237;46 245;48 22251084 The analysis of near full-length genome sequences of HIV type 1 subtype A viruses from Russia supports the monophyly of major intrasubtype clusters. These results therefore show that the monophyly of V77I(PR) and A(SP1) A(FSU) clusters is supported in near complete genomes. 2012 AIDS research and human retroviruses Abstract HIV V77I 51 55 SP1;PR 66;56 69;58 22258921 Frequency and patterns of protease gene resistance mutations in HIV-infected patients treated with lopinavir/ritonavir as their first protease inhibitor. One or more protease mutations were detected in 32 (11%) patients; the most frequent were I54V (n = 12), M46I (n = 11), V82A (n = 7) and L76V (n = 3). 2012 The Journal of antimicrobial chemotherapy Abstract HIV I54V;L76V;M46I;V82A 90;137;105;120 94;141;109;124 PR 12 20 22260721 Short communication: Drug resistance mutations in the HIV type 1 protease and reverse transcriptase genes in antiretroviral-naive Vietnamese children. In the RT gene, three major mutations were detected in six strains: the V75M mutation in one strain, the Y181C mutation in two strains, and the M184I mutation in three strains. 2012 AIDS research and human retroviruses Abstract HIV M184I;V75M;Y181C 144;72;105 149;76;110 RT 7 9 22260721 Short communication: Drug resistance mutations in the HIV type 1 protease and reverse transcriptase genes in antiretroviral-naive Vietnamese children. Minor mutations were found in the protease gene, including L10I, I13V, G16E, M36I, D60E, I62V, I64V, L63P, H69K, V82I, and I93L. 2012 AIDS research and human retroviruses Abstract HIV D60E;G16E;H69K;I13V;I62V;I64V;I93L;L10I;L63P;M36I;V82I 83;71;107;65;89;95;123;59;101;77;113 87;75;111;69;93;99;127;63;105;81;117 PR 34 42 22260721 Short communication: Drug resistance mutations in the HIV type 1 protease and reverse transcriptase genes in antiretroviral-naive Vietnamese children. Of these mutations, M36I and H69K were detected in all of the strains that were studied. 2012 AIDS research and human retroviruses Abstract HIV H69K;M36I 29;20 33;24 22264087 No increase of drug-resistant HIV type 1 prevalence among drug-naive individuals in Northern Vietnam. Nonnucleoside reverse-transcriptase inhibitor resistance mutations were found in two (2.0%) of the 102 successfully analyzed cases (one case with the Y181C and one with the K101E). 2012 AIDS research and human retroviruses Abstract HIV K101E;Y181C 173;150 178;155 NNRTI 0 35 22267476 Emerging mutations and associated factors in patients displaying treatment failure on an etravirine-containing regimen. NNRTI mutations selected were V179I (5 patients), V179L (1), V179F (2), L100I (1), K103N (2), Y181C (3), K101E (1), K101R (1) and H221Y (1). 2012 Antiviral therapy Abstract HIV H221Y;K101E;K101R;K103N;L100I;V179F;V179I;V179L;Y181C 130;105;116;83;72;61;30;50;94 135;110;121;88;77;66;35;55;99 NNRTI 0 5 22270360 Sometimes it takes two to tango: contributions of dimerization to functions of human alpha-defensin HNP1 peptide. Like the previously studied W26A mutation, N-methylation of Ile-20 dramatically reduced the ability of HNP1 to kill Staphylococcus aureus, inhibit LF, and bind gp120. 2012 The Journal of biological chemistry Abstract HIV W26A 28 32 gp120 160 165 22270360 Sometimes it takes two to tango: contributions of dimerization to functions of human alpha-defensin HNP1 peptide. N-terminal covalent tethering rescued the ability of W26A-HNP1 to inhibit LF but failed to restore its defective killing of S. 2012 The Journal of biological chemistry Abstract HIV W26A 53 57 22270360 Sometimes it takes two to tango: contributions of dimerization to functions of human alpha-defensin HNP1 peptide. The W26A and MeIle-20 mutations impaired defensin activity synergistically. 2012 The Journal of biological chemistry Abstract HIV W26A 4 8 22278243 Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus. After accounting for its inherent reverse transcription defect, HIV-1(K264E) moreover formed preintegration complexes that supported the efficient integration of endogenous viral DNA in vitro and normal levels and sequences of 2-long terminal repeat-containing circle junctions during acute infection. 2012 Journal of virology Abstract HIV K264E 70 75 RT;LTR 34;229 55;249 22278243 Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus. K264E integrase furthermore efficiently interacted in vitro with two heterologous binding partners, LEDGF/p75 and reverse transcriptase. 2012 Journal of virology Abstract HIV K264E 0 5 RT;IN 114;6 135;15 22278243 Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus. One mutant protein, K264E, in contrast, could support the wild-type level of concerted integration activity. 2012 Journal of virology Abstract HIV K264E 20 25 22278243 Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus. Our results underscore the physiological relevance of concerted integration assays for tests of integrase mutant function and suggest that the K264E mutation disrupts an interaction with an intranuclear integrase binding partner that is important for HIV-1 integration. 2012 Journal of virology Abstract HIV K264E 143 148 IN;IN 96;203 105;212 22290950 Anti-human immunodeficiency virus type 1 activity of novel 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivatives. Four additional amino acid changes (K451R, R461K, T468P, and D471N) were identified in the RNase H domain of RT; however, their precise role in the acquisition of resistance is still unclear. 2012 Antimicrobial agents and chemotherapy Abstract HIV D471N;K451R;R461K;T468P 61;36;43;50 66;41;48;55 RT 109 111 22290950 Anti-human immunodeficiency virus type 1 activity of novel 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivatives. In conclusion, the initial mutation Y181C seems sufficient for the acquisition of resistance to the uracil derivatives AzBBU and AmBBU. 2012 Antimicrobial agents and chemotherapy Abstract HIV Y181C 36 41 22290950 Anti-human immunodeficiency virus type 1 activity of novel 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivatives. The amino acid mutation Y181C in the polymerase domain of RT was detected for all escape viruses. 2012 Antimicrobial agents and chemotherapy Abstract HIV Y181C 24 29 Pol;RT 37;58 47;60 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The M184V mutation was the most frequent (n=46; 65%), followed by K103N (46%) and Y181C (21%). 2012 Antiviral therapy Abstract HIV K103N;M184V;Y181C 66;4;82 71;9;87 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Thymidine analogue mutations were infrequent (1%) and Q151M was not observed. 2012 Antiviral therapy Abstract HIV Q151M 54 59 22297391 Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. During prolonged viraemia, NRTI resistance increased (n=44, +76%), in particular thymidine analogue mutations (from 4 to 14) and K65R (from 3 to 6). 2012 Antiviral therapy Abstract HIV K65R 129 133 NRTI 27 31 22297391 Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. Initially, NNRTI-associated mutations (n=47) predominated; only 25 nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations (mainly M184V) were detected. 2012 Antiviral therapy Abstract HIV M184V 146 151 NRTI;NNRTI;NRTI 67;11;111 99;16;115 22301135 HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6. Fusion of CPSF6 residues 301 to 358 to rhesus TRIM5alpha is also sufficient to restrict wild-type but not N74D HIV-1. 2012 Journal of virology Abstract HIV N74D 106 110 22301135 HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6. HIV-1 acquires resistance to CPSF6-358 through an N74D mutation of CA that impairs binding of the antiviral factor. 2012 Journal of virology Abstract HIV N74D 50 54 Capsid 67 69 22301145 Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. 2012 Journal of virology Abstract HIV N74D 52 56 RT 188 209 22301145 Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. 2012 Journal of virology Abstract HIV N74D 51 55 Capsid;Capsid 72;80 78;82 22301145 Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages. 2012 Journal of virology Abstract HIV N74D 32 36 22301145 Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. 2012 Journal of virology Abstract HIV N74D 45 49 RT 50 71 22315096 The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors. A shift from a L89 natural polymorphism to L89I/M arose in two of five subtype C selections with PIs. 2012 The Journal of antimicrobial chemotherapy Abstract HIV L89I;L89M 43;43 49;49 PI 97 100 22315096 The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors. CONCLUSIONS: The M/L89 natural polymorphism present in non-B subtypes may lead to the M89T mutational pathway conferring resistance to atazanavir, lopinavir and nelfinavir. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M89T 86 90 22315096 The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors. M89I/V/T mutations were acquired by 10%-11% of individuals harbouring non-B subtypes who were failing PI-based regimens, but were rarely observed in drug-naive persons and in patients failing non-PI-based regimens. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M89I;M89T;M89V 0;0;0 8;8;8 PI;PI 102;196 104;198 22315096 The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors. RESULTS: The M89 natural polymorphism in non-B subtypes commonly led to the appearance of an M89T mutation in selections with atazanavir in subtypes A/AE and C, and was accompanied by other previously recognized atazanavir mutations. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M89T 93 97 22315096 The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors. The M89T mutation contributed to phenotypic resistance to atazanavir and cross-resistance to lopinavir and nelfinavir, but not to other PIs. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M89T 4 8 PI 136 139 22330916 Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation. 2012 Antimicrobial agents and chemotherapy Abstract HIV E40F;K219R;K64H;V75T;Y115F 232;255;318;238;244 236;260;322;242;249 NRTI;NRTI 294;332 298;336 22331986 HIV Drug Resistance-Associated Mutations in Antiretroviral Naive HIV-1-Infected Latin American Children. Reverse transcriptase mutations K70R and K70E were detected in 3 and 2 subjects, respectively; protease mutation I50 V was detected in 1 subject. 2010 Advances in virology Abstract HIV I50V;K70E;K70R 113;41;32 118;45;36 RT;PR 0;95 21;103 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. CONCLUSIONS: Overall, primary gp41 proteins with both V38A and N140I changes showed a reduced ability to induce single cell death and deplete CD4+ T cells, despite maintaining fusion activity. 2012 Retrovirology Abstract HIV N140I;V38A 63;54 68;58 gp41 30 34 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Conversely, Env acquiring the V38A mutation in a 140I background induced a significantly reduced loss of CD4+ T cells and lower single-cell death than did their baseline controls. 2012 Retrovirology Abstract HIV V38A 30 34 Env 12 15 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. To test this hypothesis, we have characterized the expression, fusion capability, induction of CD4+ T cell loss and single CD4+ T cell death of 48 gp41 proteins derived from three patients displaying different amino acids (N, T or I) at position 140 that developed a V38A mutation after ENF-based treatment. 2012 Retrovirology Abstract HIV V38A 267 271 gp41 147 151 22334021 Lens epithelium-derived growth factor/p75 qualifies as a target for HIV gene therapy in the NSG mouse model. Four weeks after transplantation with LEDGF(325-530)D366N cells, 70% of the CD(4)(+) cells were lost due to ongoing HIV replication. 2012 Molecular therapy Abstract HIV D366N 54 57 22334021 Lens epithelium-derived growth factor/p75 qualifies as a target for HIV gene therapy in the NSG mouse model. Here, primary human CD(4)(+) T-cells were transduced with lentiviral vectors encoding LEDGF(325-530), the interaction-deficient mutant LEDGF(325-530)D366N, or a hairpin depleting LEDGF/p75 and challenged with HIV. 2012 Molecular therapy Abstract HIV D366N 149 154 22334021 Lens epithelium-derived growth factor/p75 qualifies as a target for HIV gene therapy in the NSG mouse model. Liver and spleen sections of LEDGF(325-530) mice contained less HIV than LEDGF(325-530)D366N mice as measured by p24 antigen detection. 2012 Molecular therapy Abstract HIV D366N 87 92 p24 113 116 22334021 Lens epithelium-derived growth factor/p75 qualifies as a target for HIV gene therapy in the NSG mouse model. Threefold reduction in mean plasma viral load was obtained in mice engrafted with CD(4)(+) T-cells expressing LEDGF(325-530) in comparison with engraftment with LEDGF(325-530)D366N cells. 2012 Molecular therapy Abstract HIV D366N 175 180 22336085 Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC. However, the major polymorphisms detected in HR1: N42S, L54M, and A67T were most prevalent in subtype C (p<0.001). 2012 Journal of clinical virology Abstract HIV A67T;L54M;N42S 66;56;50 70;60;54 22336085 Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC. Mutations A316T and R315Q in gp120, which are related to MVC and VCV reduced susceptibility respectively, were predominant in subtype C (p<0.05). 2012 Journal of clinical virology Abstract HIV A316T;R315Q 10;20 15;25 gp120 29 34 22336274 [The prevalence and evolution of HIV drug-resistant strains in people who live with HIV/AIDS during HIV antiretroviral therapy in Shandong province]. M184V (48.0%, 12/25) and Y181C (32.0%, 8/25) were the most frequent mutations among 25 samples. 2011 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV Y181C;M184V 25;0 30;5 22337292 Prevalence of etravirine resistance associated mutations in HIV-1 strains isolated from infected individuals failing efavirenz: comparison between subtype B and non-B genetic variants. The most prevalent ETR RAMs observed were L100I, V90I, and K101E, with a prevalence of 16.4% (n = 9), 9.1% (n = 5), and 5.5% (n = 3), respectively. 2012 Journal of medical virology Abstract HIV K101E;L100I;V90I 59;42;49 64;47;53 22339124 The binding mode of fusion inhibitor T20 onto HIV-1 gp41 and relevant T20-resistant mechanisms explored by computational study. Also notably, the V38E and N43D mutations hindered the binding of T20 through electrostatic repulsion and thus also resulted in dramatic change in binding energy. 2012 Current HIV research Abstract HIV N43D;V38E 27;18 31;22 22339124 The binding mode of fusion inhibitor T20 onto HIV-1 gp41 and relevant T20-resistant mechanisms explored by computational study. Based on the T20-gp41 model, seven corresponding structure models of T20-resistant mutants G36D, I37K, V38E, Q39H, Q41R, N43D and L45M were constructed and fully equilibrated by MDS. 2012 Current HIV research Abstract HIV G36D;I37K;L45M;N43D;Q39H;Q41R;V38E 91;97;130;121;109;115;103 95;101;134;125;113;119;107 gp41 17 21 22339124 The binding mode of fusion inhibitor T20 onto HIV-1 gp41 and relevant T20-resistant mechanisms explored by computational study. Besides, mutations G36D, Q39H and L45M only caused minor conformational and energetic changes. 2012 Current HIV research Abstract HIV G36D;L45M;Q39H 19;34;25 23;38;29 22339124 The binding mode of fusion inhibitor T20 onto HIV-1 gp41 and relevant T20-resistant mechanisms explored by computational study. Most remarkably, the I37K and Q41R mutations led to collapse of the coiled coil structure, causing greatest change in binding energy. 2012 Current HIV research Abstract HIV I37K;Q41R 21;30 25;34 22340881 [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. 1233 sequences were then submitted to the HIV-1 drug resistance database of the Stanford University to analyze the prevalence and the emergence pattern of N348I. 2011 Zhonghua liu xing bing xue za zhi Abstract HIV N348I 155 160 22340881 [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. CONCLUSION: N348I was somehow prevalent in the therapy-failure patients when using the first-line antiretroviral drugs, and it emerged as unique patterns. 2011 Zhonghua liu xing bing xue za zhi Abstract HIV N348I 12 17 22340881 [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. N348I always emerged, and combined with others mutations among patients of ART, whose frequencies were: 85.0% in combination with thymidine analog mutations (TAMs) and 52.5% with M184V/I, respectively. 2011 Zhonghua liu xing bing xue za zhi Abstract HIV M184I;M184V;N348I 179;179;0 186;186;5 22340881 [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. OBJECTIVE: To elucidate the prevalence and the mutation pattern of N348I that related to the resistance seen in the AIDS patients, in China. 2011 Zhonghua liu xing bing xue za zhi Abstract HIV N348I 67 72 AIDS 116 120 22340881 [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. RESULTS: The prevalence of N348I was 6.5% in the therapy-failure patients and 0.8% in the naive individuals, respectively. 2011 Zhonghua liu xing bing xue za zhi Abstract HIV N348I 27 32 22340881 [Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1]. The prevalence of N348I was more popular among those patients whose ART regimens containing zidovudine (AZT or ZDV) than those without AZT in regimens (14.1% vs. 2011 Zhonghua liu xing bing xue za zhi Abstract HIV N348I 18 23 22350569 Energetic basis for drug resistance of HIV-1 protease mutants against amprenavir. Drug resistance arises from an increase in the energetic contribution from the van der Waals interactions between APV and PR (V32I, I50V, and I84V mutant) or a rise in the energetic contribution from the electrostatic interactions between the inhibitor and its target (I54M and I54V mutant). 2012 Journal of computer-aided molecular design Abstract HIV I50V;I54M;I54V;I84V;V32I 132;269;278;142;126 136;274;282;146;130 PR 122 124 22350569 Energetic basis for drug resistance of HIV-1 protease mutants against amprenavir. For the L90M mutant, a rise in the van der Waals energy for APV-PR interactions is compensated by a decrease in the polar solvation free energy such that the net binding affinity remains unchanged. 2012 Journal of computer-aided molecular design Abstract HIV L90M 8 12 PR 64 66 22350569 Energetic basis for drug resistance of HIV-1 protease mutants against amprenavir. For the V32I mutant, also an increased free energy for the polar solvation contributes to the drug resistance. 2012 Journal of computer-aided molecular design Abstract HIV V32I 8 12 22350569 Energetic basis for drug resistance of HIV-1 protease mutants against amprenavir. However, the affinities of the drug resistant protease variants V32I, I50V, I54V, I54M, I84V and L90M to amprenavir are decreased 3 to 30-fold compared to the wild-type. 2012 Journal of computer-aided molecular design Abstract HIV I50V;I54M;I54V;I84V;L90M;V32I 70;82;76;88;97;64 74;86;80;92;101;68 PR 46 54 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Overall, 3/36(8.3%) subjects had DRMs identified with Stanford-HIVdb weights >12 for ATV or LPV: N88S (at 0.43% level-mutational load 1,828) in 1 subject on ATV; I50V (0.44%-mutational load 110) and L76V (0.52%-mutational load 20) in 1 subject each, both on LPV. 2012 PloS one Abstract HIV I50V;L76V;N88S 162;199;97 166;203;101 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. The most common UDS-detected DRM were NRTI in 18 subjects: M184V/I (11), TAMs(7) & K65R(4); PI DRMs were detected in 9 subjects: M46I/V(5), F53L(2), I50V(1), D30N(1), and N88S(1). 2012 PloS one Abstract HIV D30N;F53L;I50V;K65R;M184I;M184V;M46I;M46V;N88S 158;140;149;83;59;59;129;129;171 162;144;153;87;66;66;135;135;175 NRTI;PI 38;92 42;94 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. The remaining 12 subjects, all with VLs<10,000, had protease gene UDS, and 4 had low-level PI DRMs: F53L(2), L76V(1), I54S(1), G73S(1). 2012 PloS one Abstract HIV F53L;G73S;I54S;L76V 100;127;118;109 104;131;122;113 PR;PI 52;91 60;93 22358416 Prevalence and patterns of HIV transmitted drug resistance in Guatemala. Major NNRTI mutations such as K101E, K103N, and E138K showed higher frequencies than expected in ART-naive populations. 2011 Revista panamericana de salud publica Abstract HIV E138K;K101E;K103N 48;30;37 53;35;42 NNRTI 6 11 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. Baseline drug resistance to nucleoside reverse transcriptase inhibitors was observed in 54.5% of cases (mutations: M41L, K103N, T215S/D) with evidence of clustering, no baseline integrase or protease resistance and infrequent non-R5 tropism (13.6%). 2012 PloS one Abstract HIV K103N;M41L;T215D;T215S 121;115;128;128 126;119;135;135 NRTI;IN;PR 28;178;191 60;187;199 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. BACKGROUND: We previously demonstrated in vitro that zidovudine (AZT) selects for A371V in the connection domain and Q509L in ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) which, together with the thymidine analog mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. 2012 PloS one Abstract HIV A371V;D67N;K70R;Q509L;T215F 82;246;252;117;261 87;250;256;122;266 RT;RT 167;190 188;192 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Biochemical studies revealed that A360V enhances the AZT-monophosphate excision activity of purified RT by significantly decreasing the frequency of secondary RNase H cleavage events that reduce the RNA/DNA duplex length and promote template/primer dissociation. 2012 PloS one Abstract HIV A360V 34 39 RT 101 103 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. CONCLUSIONS: The A360V mutation in the connection domain of RT was selected in HIV-infected individuals that received AZT monotherapy and contributed to AZT resistance. 2012 PloS one Abstract HIV A360V 17 22 RT 60 62 HIV infections 79 91 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. HIV-1 drug susceptibility assays demonstrated that A360V, either alone or in combination with thymidine analog mutations, decreased AZT susceptibility in recombinant viruses containing participant-derived full-length RT sequences or site-directed mutant RT. 2012 PloS one Abstract HIV A360V 51 56 RT;RT 217;254 219;256 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Mutations significantly associated with AZT monotherapy included K70R (p = 0.003) and T215Y (p = 0.013) in the polymerase domain of HIV-1 RT, and A360V (p = 0.041) in the connection domain of HIV-1 RT. 2012 PloS one Abstract HIV A360V;K70R;T215Y 146;65;86 151;69;91 Pol;RT;RT 111;138;198 121;140;200 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V, Q509L or other mutations in the C-terminal domains of HIV-1 RT. 2012 PloS one Abstract HIV A371V;Q509L 115;122 120;127 RT 182 184 HIV infections 74 88 22365617 [Use of an empirical antiretroviral treatment depends on the primary resistance rate of the human immunodeficiency virus]. After starting antiretroviral therapy, the resistance analyses detected the existence of primary resistance to antiretrovirals in 12.7% (confidence interval 95%: 3-22) of the patients, distributed as follows: isolated resistance to, nucleosides was detected in 2% (M184V), to nevirapine/efavirenz in 9% (K103N), and combined resistance to nucleosides and non-nucleosides in 2%; there were no cases of resistance to protease inhibitors. 2012 Enfermedades infecciosas y microbiologia clinica Abstract HIV K103N;M184V 304;265 309;270 PR 415 423 22371439 Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens. OBJECTIVES: To compare the frequency of the selection of the M184V/I resistance mutation in HIV-infected patients who experienced virological failure while receiving emtricitabine (FTC) or lamivudine (3TC), administered with tenofovir disoproxil fumarate (TDF) and either efavirenz (EFV) or a ritonavir-boosted protease inhibitor (PI; lopinavir or atazanavir). 2012 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 61;61 68;68 PR;PI 311;331 319;333 HIV infections 92 104 22371439 Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens. Proportions of patients harbouring the M184V/I mutation were 24% (n = 62) for those who received FTC + TDF + EFV versus 51% (n = 91) for 3TC + TDF + EFV (P < 0.0001; Fisher's exact test); proportions were 11% (n = 30) for FTC + TDF + ritonavir-boosted PI versus 22% (n = 37) for 3TC + TDF + ritonavir-boosted PI (P = 0.002; Fisher's exact test). 2012 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 39;39 46;46 PI;PI 252;309 254;311 22371439 Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens. The prevalence of the M184V/I resistance mutation was significantly lower in patients who received emtricitabine and tenofovir disoproxil fumarate than in those who received lamivudine and tenofovir disoproxil fumarate. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 22;22 29;29 22371439 Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens. The use of lamivudine versus emtricitabine (P = 0.001), non-nucleoside reverse transcriptase inhibitors versus ritonavir-boosted PIs (P = 0.01) and the level of viral load at the time of virological failure (P = 0.01) were associated with selection of the M184V/I mutation (logistic regression analysis). 2012 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 256;256 263;263 NNRTI;PI 56;129 92;132 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. Based on these results, we propose that enhanced RNase H cleavage near the primer terminus plays a role in M184V suppression of AZT resistance, while K65R suppression occurs through a different mechanism. 2012 Journal of virology Abstract HIV K65R;M184V 150;107 154;112 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. Cleavage at the initial site was followed by RT dissociation and rebinding at the -7 cleavage site, and the dissociation and rebinding were enhanced when the M184V mutation was present. 2012 Journal of virology Abstract HIV M184V 158 163 RT 45 47 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. In contrast to the effect of M184V, the K65R mutation suppressed the excision activity of RT to the same extent on either an RNA or a DNA template and did not alter the RNase H cleavage pattern. 2012 Journal of virology Abstract HIV K65R;M184V 40;29 44;34 RT 90 92 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. In RT containing TAMs, the addition of M184V suppressed the excision of 3'-deoxy-3'-azidothymidine monophosphate (AZTMP) to a greater extent on an RNA template than on a DNA template with the same sequence. 2012 Journal of virology Abstract HIV M184V 39 44 RT 3 5 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. The catalytically inactive RNase H mutation E478Q abolished this difference. 2012 Journal of virology Abstract HIV E478Q 44 49 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. The RT mutation M184V is a potent suppressor of TAMs. 2012 Journal of virology Abstract HIV M184V 16 21 RT 4 6 22379084 A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation. Whether M184V was present or not, RT did not initially bind at the -7 cleavage site. 2012 Journal of virology Abstract HIV M184V 8 13 RT 34 36 22382470 Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients. CONCLUSIONS: In our series, the M426L substitution in the gp120 region was detected in 46% and 7% of subtype D and CRF02_AG samples, respectively, and might affect the activity of BMS-626529 against these specific subtypes. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M426L 32 37 gp120 58 63 22382470 Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients. Mutations selected during in vitro experiments with BMS-626529 are located in the gp120 region: L116P, A204D, M426L, M434I-V506M and M475I. 2012 The Journal of antimicrobial chemotherapy Abstract HIV A204D;L116P;M426L;M434I;M475I;V506M 103;96;110;117;133;123 108;101;115;122;138;128 gp120 82 87 22382470 Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients. None of the CRF02_AG viruses harboured both M426L and M434I substitutions. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M426L;M434I 44;54 49;59 22382470 Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients. The M426L substitution was found in virus from 10 patients (11.8%), mainly in subtypes D and CRF02_AG. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M426L 4 9 22382470 Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients. The M434I substitution was found in virus from 11 patients (12.9%), mainly in subtypes CRF02_AG and CRF06_cpx. 2012 The Journal of antimicrobial chemotherapy Abstract HIV M434I 4 9 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of <1%. 2012 PloS one Abstract HIV K70R;T215F;T215Y;K103N;M184V;Y181C 208;219;213;232;254;238 212;224;218;237;259;243 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Even though Vpx K84A lacked ubiquitination, it bound DCAF1, and infected macrophages comparable to Wt Vpx. 2012 Virology Abstract HIV K84A 16 20 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. However, ubiquitination was absent with Vpx TA and Vpx K84A mutants, indicating a lack of ubiquitin on positions K68 and K77. 2012 Virology Abstract HIV K84A 55 59 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Mutants Vpx K68A and K77A were unable to infect macrophages due to impaired reverse transcription from loss of interaction with the ubiquitin substrate receptor, DCAF1. 2012 Virology Abstract HIV K68A;K77A 12;21 16;25 RT 76 97 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Crystal structures at resolutions of 1.25-1.55 A were analyzed for complexes of 1 with the PR containing major drug resistant mutations, PR(I47V), PR(L76V), PR(V82A), and PR(N88D). 2012 Journal of medicinal chemistry Abstract HIV I47V;L76V;N88D;V82A 140;150;174;160 144;154;178;164 PR;PR;PR;PR;PR 91;137;147;157;171 93;139;149;159;173 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Mutations of I47V and V82A alter residues in the inhibitor-binding site, while L76V and N88D are distal mutations having no direct contact with the inhibitor. 2012 Journal of medicinal chemistry Abstract HIV I47V;L76V;N88D;V82A 13;79;88;22 17;83;92;26 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Substitution of a smaller amino acid in PR(I47V) and PR(L76V) and the altered charge of PR(N88D) are associated with significant local structural changes compared to the wild-type PR(WT), while substitution of alanine in PR(V82A) increases the size of the S1' subsite. 2012 Journal of medicinal chemistry Abstract HIV I47V;L76V;N88D;V82A 43;56;91;224 47;60;95;228 PR;PR;PR;PR;PR 40;53;88;180;221 42;55;90;182;223 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. In particular, insertion of the large aromatic side chains of L10F and L33F alters intersubunit interactions and widens the PI binding site through a network of hydrophobic contacts. 2012 Biochemistry Abstract HIV L10F;L33F 62;71 66;75 PI 124 126 22405288 Synthesis and biological evaluation of piperidine-substituted triazine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors. Most compounds displayed extremely promising activity against wild-type HIV-1 with EC(50) values in low nanomolar concentration, better than that of Nevirapine, Delavirdine, Zidovudine and Dideoxycitidine, and higher potency towards the resistant mutant strain K103N/Y181C than that of Nevirapine and Delavirdine. 2012 European journal of medicinal chemistry Abstract HIV K103N;Y181C 261;267 266;272 22417570 Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy. Among patients treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) and with thymidine analogues (TA) experience, TAMs1 M41L and L210W were less prevalent in CRF02_AG, while TAMs2 T215F and K219E were more prevalent in the F subtype. 2012 AIDS research and human retroviruses Abstract HIV K219E;L210W 212;151 217;156 RT;NRTI 50;84 71;88 22417570 Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy. In non-NRTI (NNRTI)-treated patients infected by the C subtype the prevalence of K103N was lower than in patients infected with other subtypes, while the prevalence of Y181C and Y188L was higher compared to subtype B. 2012 AIDS research and human retroviruses Abstract HIV K103N;Y181C;Y188L 81;168;178 86;173;183 NNRTI;NNRTI 3;13 11;18 22417570 Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy. In NRTI-treated patients having experience with abacavir, didanosine, tenofovir, or stavudine the K65R mutation was mostly prevalent in the C subtype. 2012 AIDS research and human retroviruses Abstract HIV K65R 98 102 NRTI 3 7 22417570 Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy. In patients treated with protease inhibitors, L89V was predominantly found in CRF02_AG, while the TPV resistance mutation T74P was predominantly found in the C subtype. 2012 AIDS research and human retroviruses Abstract HIV L89V;T74P 46;122 50;126 PR 25 33 22417570 Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy. The prevalence of Y181C was higher also in subtype F as compared to subtype B. 2012 AIDS research and human retroviruses Abstract HIV Y181C 18 23 22419605 Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors. Previous studies aimed at exploring the SAR of C2-functionalized S-DABOs demonstrated that the substituent at this position plays a key role in the inhibition of both wild-type RT and drug-resistant enzymes, particularly the K103N mutant form. 2012 ChemMedChem Abstract HIV K103N 225 230 RT 177 179 22419605 Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors. The introduction of a cyclopropyl group led us to the discovery of a potent inhibitor with picomolar activity against wild-type RT and nanomolar activity against many key mutant forms such as K103N. 2012 ChemMedChem Abstract HIV K103N 192 197 RT 128 130 22431018 Minority HIV-1 resistant variants in recent infection and in patients who failed first-line antiretroviral therapy with no detectable resistance-associated mutations in Thailand. 1/104 (0.5%) and 3/101 (3%) samples were found harboring Y181C and M184V in the group of homosexual men recently infected with HIV-1. 2012 Journal of medical virology Abstract HIV M184V;Y181C 67;57 72;62 22431018 Minority HIV-1 resistant variants in recent infection and in patients who failed first-line antiretroviral therapy with no detectable resistance-associated mutations in Thailand. In patients with first-line treatment failure, one had a minority M184V mutation (4.5%). 2012 Journal of medical virology Abstract HIV M184V 66 71 22431018 Minority HIV-1 resistant variants in recent infection and in patients who failed first-line antiretroviral therapy with no detectable resistance-associated mutations in Thailand. Pyrosequencing (PSQ) assay was developed to detect and quantify minority Y181C and M184V variants from the patients' plasma samples. 2012 Journal of medical virology Abstract HIV M184V;Y181C 83;73 88;78 22431018 Minority HIV-1 resistant variants in recent infection and in patients who failed first-line antiretroviral therapy with no detectable resistance-associated mutations in Thailand. The prevalence of Y181C and M184V minority variants in homosexual men recently infected and naive to treatment was low in Thailand. 2012 Journal of medical virology Abstract HIV M184V;Y181C 28;18 33;23 22431018 Minority HIV-1 resistant variants in recent infection and in patients who failed first-line antiretroviral therapy with no detectable resistance-associated mutations in Thailand. The sensitivity of PSQ to detect minority Y181C and M184V variants was approximately 1%. 2012 Journal of medical virology Abstract HIV M184V;Y181C 52;42 57;47 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. One cluster contained 18 viruses with a M41L resistance mutation, which had spread among MSM in Stockholm over a period of at least 16 years (1994-2010). 2012 PloS one Abstract HIV M41L 40 44 22449200 Tax gene characterization of human T-lymphotropic virus type 1 strains from Brazilian HIV-coinfected patients. Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. 2012 AIDS research and human retroviruses Abstract HIV A8367C;C7401T;C7920T;C7982T;G8231A;T7914C 139;95;111;119;127;103 145;101;117;125;133;109 22451677 Signals in APOBEC3F N-terminal and C-terminal deaminase domains each contribute to encapsidation in HIV-1 virions and are both required for HIV-1 restriction. Analysis of the A3F (W126A L306A) double mutant revealed that both residues are required for full anti-HIV function. 2012 The Journal of biological chemistry Abstract HIV L306A;W126A 27;21 32;27 22456540 Genetic barrier to the development of resistance to integrase inhibitors in HIV-1 subtypes CRF01_AE and B. At six codon positions with different genetic barriers, six mutations (V72I, L101I, A124T, T125K, and G140C/S) displayed a higher genetic barrier and one mutation (V201I) showed a lower genetic barrier in subtype CRF01_AE than subtype B. 2012 Intervirology Abstract HIV A124T;G140C;G140S;L101I;T125K;V201I;V72I 84;102;102;77;91;164;71 89;109;109;82;96;169;75 22456540 Genetic barrier to the development of resistance to integrase inhibitors in HIV-1 subtypes CRF01_AE and B. Nevertheless, different genetic barriers were observed in two mutations described to be associated with DTG resistance (L101I, A124T) and other five RAL and EVG secondary mutations (V72I, T125K, G140C/S, V201I), which could have an impact on the development of resistance to RAL, EVG, and DTG. 2012 Intervirology Abstract HIV A124T;G140C;G140S;L101I;T125K;V201I;V72I 127;195;195;120;188;204;182 132;202;202;125;193;209;186 22457522 Deep sequencing reveals minor protease resistance mutations in patients failing a protease inhibitor regimen. Eligibility criteria were virologic failure (HIV-1 RNA load of >500 copies/ml) of a first-line nonnucleoside reverse transcriptase inhibitor-based regimen, with at least the M184V mutation (lamivudine resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based regimen. 2012 Journal of virology Abstract HIV M184V 174 179 NNRTI 95 130 22473024 HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. 2012 Antiviral therapy Abstract HIV D67N;G190A;K103N;K219R;L74V;M184I;M184V;T69D;V106M;V75M;Y181C;Y181C;Y188C 308;269;238;165;141;153;153;135;245;147;252;317;259 313;274;243;170;145;160;160;139;250;151;257;322;264 NNRTI;RT;PR;NNRTI;NNRTI;NRTI;NRTI 181;94;336;230;300;128;290 217;115;344;236;306;133;295 22474222 Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). 2012 Clinical infectious diseases Abstract HIV K65R 0 4 22474222 Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). 2012 Clinical infectious diseases Abstract HIV G190A;K103N;M184V;Y181C 75;41;26;56 80;46;31;61 22485165 BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. 2012 PloS one Abstract HIV V151I 13 18 IN 84 86 22490797 [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. CONCLUSION: With a unique mutation pattern, H221Y has a low prevalence in the individuals of first-line therapy-failure patients. 2012 Zhonghua yi xue za zhi Abstract HIV H221Y 44 49 22490797 [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. Frequency of H221Y in the regimen of AZT/ddI/NVP was more popular than the other 4 regimens (14.6% vs 3.5%, 4.9%, 2.3%, 2.6%, all P < 0.01). 2012 Zhonghua yi xue za zhi Abstract HIV H221Y 13 18 22490797 [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. METHODS: A total of 1363 sequences, comprising of 1205 therapy-failure individuals and 158 therapy-naive individuals, were submitted to the Stanford HIV drug resistance database (SHDB) to analyze the frequency and mutation pattern of H221Y. 2012 Zhonghua yi xue za zhi Abstract HIV H221Y 234 239 22490797 [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. OBJECTIVE: To explore the prevalence and mutation pattern of H221Y at reverse transcriptase (RT) among the subtype B' of human immunodeficiency virus1 (HIV-1) in antiviral therapy-failure patients. 2012 Zhonghua yi xue za zhi Abstract HIV H221Y 61 66 RT;RT 70;93 91;95 22490797 [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. RESULTS: The prevalence of mutation H221Y in the therapy-failure population was significantly higher than that of the therapy-naive (6.59% vs 0.60%) (chi(2) = 6.59, P = 0.027). 2012 Zhonghua yi xue za zhi Abstract HIV H221Y 36 41 22490797 [Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1]. The emergence of H221Y usually accompanied the position mutations of T215, M184, K103 and Y181 of RT, and the pattern of TAMs/H221Y/Y181C/I was common. 2012 Zhonghua yi xue za zhi Abstract HIV H221Y;Y181C;Y181I;H221Y 126;132;132;17 131;139;139;22 RT 98 100 22491471 Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures. Enfuvirtide was added to the antiretroviral regimen at week 30; by week 48, enfuvirtide treatment selected for either the G36D or N43D HR-1 mutation. 2012 Journal of virology Abstract HIV G36D;N43D 122;130 126;134 22491471 Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures. The correction of N43D, in contrast, restored fitness relative to that of week 28, but not week 0, viruses. 2012 Journal of virology Abstract HIV N43D 18 22 22491471 Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures. This week 48 fitness deficit persisted when G36D was corrected by either site-directed mutagenesis or week 48 gp41 domain swapping. 2012 Journal of virology Abstract HIV G36D 44 48 gp41 110 114 22492850 Effects of short-course zidovudine on the selection of nevirapine-resistant HIV-1 in women taking single-dose nevirapine. HIV-1 infected pregnant women administered sdNVP with or without short-course ZDV were assessed for HIV-1 mutations (K103N, Y181C, G190A, and V106M) prior to delivery and postpartum. 2012 The Journal of infectious diseases Abstract HIV G190A;K103N;V106M;Y181C 131;117;142;124 136;122;147;129 HIV infections 0 14 22493227 Transition states of native and drug-resistant HIV-1 protease are the same. The KIEs measured for the native and I84V enzyme indicate nearly identical transition states, implying that a true transition-state analogue should be effective against both enzymes. 2012 Proc Natl Acad Sci U S A Abstract HIV I84V 37 41 22493227 Transition states of native and drug-resistant HIV-1 protease are the same. We have measured primary (14)C and (15)N KIEs and secondary (3)H and (18)O KIEs for native and multidrug-resistant HIV-1 protease (I84V). 2012 Proc Natl Acad Sci U S A Abstract HIV I84V 131 135 PR 121 129 22493227 Transition states of native and drug-resistant HIV-1 protease are the same. We observed (14)C KIEs ((14)V/K) of 1.029 +- 0.003 and 1.025 +- 0.005, (15)N KIEs ((15)V/K) of 0.987 +- 0.004 and 0.989 +- 0.003, (18)O KIEs ((18)V/K) of 0.999 +- 0.003 and 0.993 +- 0.003, and (3)H KIEs ((3)V/K) KIEs of 0.968 +- 0.001 and 0.976 +- 0.001 for the native and I84V enzyme, respectively. 2012 Proc Natl Acad Sci U S A Abstract HIV I84V 273 277 22496233 Uncommon pathways of immune escape attenuate HIV-1 integrase replication capacity. An NL4-3 mutant encoding the S119R polymorphism displayed a ~35%-reduced function that was rescued by a single compensatory mutation of A91E. 2012 Journal of virology Abstract HIV A91E;S119R 136;29 140;34 22496233 Uncommon pathways of immune escape attenuate HIV-1 integrase replication capacity. Notably, the integrase variants S119R, G163E, and I220L, which represent uncommon polymorphisms associated with HLA-C*05, -A*33, and -B*52, respectively, correlated with lower RC (all q < 0.2). 2012 Journal of virology Abstract HIV G163E;I220L;S119R 39;50;32 44;55;37 IN 13 22 22496233 Uncommon pathways of immune escape attenuate HIV-1 integrase replication capacity. We identified a novel C*05-restricted epitope (HTDNGSNF(114-121)) that likely contributes to the selection of the S119R variant, the polymorphism most significantly associated with lower RC in patient sequences. 2012 Journal of virology Abstract HIV S119R 114 119 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. No difference in the capacity to detect resistance associated with M184V, K103N and V106M mutations was noted between the two backbones. 2012 PloS one Abstract HIV K103N;M184V;V106M 74;67;84 79;72;89 22496972 Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India. One patient had a major RT mutation M184V, known to confer resistance to lamivudine, and another had a major protease inhibitor (PI) mutation D30N that imparts resistance to nelfinavir. 2012 AIDS research and treatment Abstract HIV D30N;M184V 142;36 146;41 PR;PI;RT 109;129;24 117;131;26 22497664 Genetic diversity and naturally polymorphisms in HIV type 1 integrase isolates from Maputo, Mozambique: implications for integrase inhibitors. No major mutations conferring resistance to integrase inhibitors were found and polymorphic accessory mutations were solely observed in low frequency among subtype C sequences-L74M (3.4%), T97A (1.8%), and E157Q (1.8%)-suggesting that this new antiretroviral drug class will be effective in Mozambique providing a good perspective to the introduction of this class of drugs in that country. 2012 AIDS research and human retroviruses Abstract HIV E157Q;L74M;T97A 206;176;189 211;180;193 IN 44 53 22504392 Study of drug resistance among 78 antiretroviral treatment-naive patients with HIV-1 subtype B infection in central China. The major mutations, which were mainly K103N and Q151M, were less frequent in China than those in other countries. 2007 Drug discoveries & therapeutics Abstract HIV K103N;Q151M 39;49 44;54 22504392 Study of drug resistance among 78 antiretroviral treatment-naive patients with HIV-1 subtype B infection in central China. The most common mutations were L63P, V77I and I93L, which belong to minor mutations of the proteinase gene, and none of which had any relation to viral loads. 2007 Drug discoveries & therapeutics Abstract HIV I93L;L63P;V77I 46;31;37 50;35;41 22504392 Study of drug resistance among 78 antiretroviral treatment-naive patients with HIV-1 subtype B infection in central China. There was a certain correlation between viral loads and I93IL according to stepwise regression analysis. 2007 Drug discoveries & therapeutics Abstract HIV I93I;I93L 56;56 61;61 22512366 Etravirine: a review of its use in the management of treatment-experienced patients with HIV-1 infection. Importantly, the most prevalent NNRTI-associated mutation, K103N, alone does not affect the etravirine response. 2012 Drugs Abstract HIV K103N 59 64 NNRTI 32 37 22513406 Balancing antiviral potency and host toxicity: identifying a nucleotide inhibitor with an optimal kinetic phenotype for HIV-1 reverse transcriptase. We also show that the pol gamma mutation R964C, which predisposes patients to mitochondrial toxicity when receiving 2',3'-didehydro-2',3'-dideoxythymidine to treat HIV, produced some loss of discrimination for FLT-TP and Ed4T-TP. 2012 Molecular pharmacology Abstract HIV R964C 41 46 Pol 22 25 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Analysis of the corresponding purified N-terminal domain CA proteins by NMR spectroscopy demonstrated that the E45A and R132T mutations induced structural changes that are localized to the regions of the mutations, while the P38A mutation resulted in changes extending to neighboring regions in space. 2012 Retrovirology Abstract HIV E45A;P38A;R132T 111;225;120 115;229;125 Capsid 57 59 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. CONCLUSIONS: The second-site suppressor mutations in CA that we have identified rescue virus infection without correcting the intrinsic capsid stability defects associated with the P38A and E45A mutations. 2012 Retrovirology Abstract HIV E45A;P38A 190;181 194;185 Capsid;Capsid 136;53 142;55 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Nonetheless, the R132T mutation rescued the selective infectivity impairment exhibited by the E45A mutant in aphidicolin-arrested cells, and the double mutant regained sensitivity to the small molecule inhibitor PF74. 2012 Retrovirology Abstract HIV E45A;R132T 94;17 98;22 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. RESULTS: To further examine the connection between HIV-1 capsid stability and infectivity, we isolated second-site suppressors of HIV-1 mutants exhibiting unstable (P38A) or hyperstable (E45A) capsids. 2012 Retrovirology Abstract HIV E45A;P38A 187;165 191;169 Capsid;Capsid 57;193 63;200 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The T216I mutation rescued the impaired ability of the P38A mutant virus to abrogate restriction by TRIMCyp and TRIM5alpha. 2012 Retrovirology Abstract HIV P38A;T216I 55;4 59;9 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. We identified the respective suppressor mutations, T216I and R132T, which restored virus replication in a human T cell line and markedly enhanced the fitness of the original mutants as revealed in single-cycle infection assays. 2012 Retrovirology Abstract HIV R132T;T216I 61;51 66;56 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. 2012 Virology Abstract HIV T244A 104 109 gp120 97 102 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. 2012 Virology Abstract HIV F519I;G516V;M518V 143;23;134 148;28;139 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. 2012 Virology Abstract HIV G516V 68 73 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. 2012 Virology Abstract HIV F519I 29 34 22530020 Counteraction of tetherin antiviral activity by two closely related SIVs differing by the presence of a Vpu gene. Simultaneous mutation (P40L and T45I) of human tetherin conferred sensitivity to SIVden Vpu, while abolishing its sensitivity to HIV-1 Vpu. 2012 PloS one Abstract HIV P40L;T45I 23;32 28;36 Vpu;Vpu 88;135 91;138 22534017 Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation. RESULTS: To identify Nef binding partners involved in Pak2-association dependent Nef functions, we employed tandem mass spectrometry analysis of Nef immunocomplexes from Jurkat cells expressing wild-type Nef or Nef mutants defective for the ability to associate with Pak2 (F85L, F89H, H191F and A72P, A75P in NL4-3). 2012 Retrovirology Abstract HIV A72P;A75P;F85L;F89H;H191F 295;301;273;279;285 299;305;277;283;290 Nef;Nef;Nef;Nef;Nef 21;81;145;204;211 24;84;148;207;214 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. 12 strains containing different drug-resistant mutation profiles were constructed, including the K101Q series (K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, and K101Q), the V179D series (V179D/Y181C/H221Y, V179D/Y181C, V179D/H221Y, and V179D), and the K103N series (K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y, K103N). 2012 AIDS research and treatment Abstract HIV K101Q;H221Y;H221Y;H221Y;K103N;V179D;Y181C;Y181C;Y181C;H221Y;H221Y;H221Y;K101Q;K101Q;K101Q;K101Q;K103N;K103N;K103N;K103N;V179D;V179D;V179D;V179D;Y181C;Y181C;Y181C 111;198;277;123;265;186;117;192;271;224;149;303;97;130;143;160;251;297;310;284;172;235;205;218;136;211;290 116;203;282;128;270;191;122;197;276;229;154;308;102;135;148;165;256;302;315;289;177;240;210;223;141;216;295 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. For strains containing the mutation profiles (K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N), the presence of H221Y reduced NVP susceptibility by 2.1 +- 0.5 to 3.6 +- 0.5 fold. 2012 AIDS research and treatment Abstract HIV K101Q;H221Y;K101Q;K103N;K103N;V179D;V179D;Y181C;Y181C;Y181C 46;127;59;86;103;66;79;52;72;92 51;132;64;91;108;71;84;57;77;97 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. For the strains containing K101Q, V179D, and K103N, the presence of Y181C/H221Y combination decreased NVP susceptibility by 100.6 +- 32.5 to 3444.6 +- 834.5 fold. 2012 AIDS research and treatment Abstract HIV H221Y;K101Q;K103N;V179D;Y181C 74;27;45;34;68 79;32;50;39;73 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. H221Y and (or) Y181C mutations were reverted to wild type amino acids by site-directed mutagenesis, then strains containing various mutation patterns were packaged. 2012 AIDS research and treatment Abstract HIV Y181C;H221Y 13;0 20;5 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. On the bases of various NNRTIs mutation profiles, Y181C remarkably improved the IC(50) to NVP, although H221Ymutation alone just increases 2.1 ~ 3.6-fold resistance to NVP, the mutation could improve 100.6 ~ 3444.6-fold resistance to NVP when it copresent with Y181C, the phenotypic drug resistance fold was improved extremely. 2012 AIDS research and treatment Abstract HIV Y181C;Y181C 50;261 55;266 NNRTI 24 30 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. To clarify the impact of H221Y mutation on drug resistance to NVP. 2012 AIDS research and treatment Abstract HIV H221Y 25 30 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. To the mutation profiles K101Q/H221Y, K101Q, V179D/H221Y, V179D, K103N/H221Y, and K103N, the presence of Y181C reduced NVP susceptibility by 41.9 +- 8.4 to 1297.0 +- 289.1 fold. 2012 AIDS research and treatment Abstract HIV H221Y;H221Y;H221Y;K101Q;K101Q;K103N;K103N;V179D;V179D;Y181C 31;51;71;25;38;65;82;45;58;105 36;56;76;30;43;70;87;50;63;110 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. In addition, in the 2008-2009 study, 5.3% of the parasite samples carried the dhps triple mutant (A437G/K540E/A581G). 2012 Malaria journal Abstract HIV A437G;A581G;K540E 98;110;104 103;115;109 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. RESULTS: The prevalence of quintuple mutant (dhfr N51I/C59R/S108N and dhps A437G/K540E combined genotype) increased from 7% in the first study (1996-2000) to 88% in the third study (2008-2009). 2012 Malaria journal Abstract HIV C59R;N51I;S108N;A437G;K540E 55;50;60;75;81 59;54;65;80;86 22544694 HIV genotype resistance testing in antiretroviral (ART) exposed Indian children--a need of the hour. GRT was specifically important for the selection of a new dual Nucleoside reverse transcriptase inhibitors (NRTI) component of failure regimen by identifying TAMS and M184V mutations in the HIV genome. 2013 Indian journal of pediatrics Abstract HIV M184V 167 172 NRTI;NRTI 63;108 95;112 22549928 Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease. Structural analysis of the designed complexes revealed that one of the engineered substitutions (G48R) potentially stabilized heterogeneous flap conformations, thereby facilitating alternate modes of substrate binding. 2012 Protein science Abstract HIV G48R 97 101 22549928 Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease. The engineered variant, Pr3 (A28S/D30F/G48R), was designed to preferentially bind to one out of three of HIV protease's natural substrates; RT-RH over p2-NC and CA-p2. 2012 Protein science Abstract HIV A28S;D30F;G48R 29;34;39 33;38;43 PR;NC;Capsid;PR;RT 109;154;161;24;140 117;156;163;26;142 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. CONCLUSIONS: The mutations H105Y, V255M, S375R/N, G471R/E, and D474N are found to be involved in resistance towards M48 and M48U1. 2012 Retrovirology Abstract HIV D474N;G471E;G471R;H105Y;S375N;S375R;V255M 63;50;50;27;41;41;34 68;57;57;32;48;48;39 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Resistance against M48U1 was always associated with S375R/N substitution in both BaL and SF162; M48 resistance was associated with D474N substitution in SF162 and with H105Y substitution in BaL. 2012 Retrovirology Abstract HIV D474N;H105Y;S375N;S375R 131;168;52;52 136;173;59;59 22553319 Immune selection in vitro reveals human immunodeficiency virus type 1 Nef sequence motifs important for its immune evasion function in vivo. Functional testing of naturally occurring in vivo polymorphisms at the 7 sites with no previously known functional role revealed 3 mutations (A84D, Y135F, and G140R) that ablated MHC-I downregulation and 3 (N52A, S169I, and V180E) that partially impaired MHC-I downregulation. 2012 Journal of virology Abstract HIV A84D;G140R;N52A;S169I;V180E;Y135F 142;159;207;213;224;148 146;164;211;218;229;153 22553340 Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo. Evaluation of molecular clones isolated from different time points demonstrated that Y143R and Q148H variants exhibited larger reductions in RAL susceptibility and higher IN-mediated replication capacity (RC) than N155H variants within the same subject. 2012 Journal of virology Abstract HIV N155H;Q148H;Y143R 214;95;85 219;100;90 IN 171 173 22553340 Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo. Furthermore, shifts from the N155H pathway to either the Q148R or H pathway or the Y143R pathway were dependent on the amino acid substitution at position 148 and the secondary mutations in Y143R- or Q148R- or H-containing variants and correlated with reductions in RAL susceptibility and restorations in RC. 2012 Journal of virology Abstract HIV N155H;Q148R;Q148R;Y143R;Y143R 29;57;200;83;190 34;62;205;88;195 22553340 Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo. Patient viruses containing Y143R, Q148R, or Q148H mutations consistently exhibited larger reductions in RAL susceptibility than patient viruses containing N155H mutations. 2012 Journal of virology Abstract HIV N155H;Q148H;Q148R;Y143R 155;44;34;27 160;49;39;32 22553340 Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo. Sequential analyses of virus populations from three subjects revealed temporal shifts in subpopulations representing N155H, Y143R, or Q148H escape pathways. 2012 Journal of virology Abstract HIV N155H;Q148H;Y143R 117;134;124 122;139;129 22553340 Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo. These selective pressures result in the displacement of N155H variants by 143 or 148 variants under continued drug exposure. 2012 Journal of virology Abstract HIV N155H 56 61 22563717 HIV type 1 virological response and prevalence of HIV type 1 drug resistance among patients receiving antiretroviral therapy, Shandong, China. The most common mutations were thymidine-analog mutations (22.5%) and M184V (10%) to nucleoside reverse transcriptase inhibitors (NRTIs), and V106I/A /M (17.5%), Y181C (15%), and H221Y (12.5%) to non-NRTIs (NNRTIs); 13 patients had mutations to both NRTIs and NNRTIs. 2012 AIDS research and human retroviruses Abstract HIV H221Y;M184V;V106A;V106I;Y181C 179;70;142;142;162 184;75;149;149;167 NRTI;NNRTI;NNRTI;NNRTI;NRTI;NRTI 85;196;207;260;130;250 117;205;213;266;135;255 22564075 A trimer of dimers is the basic building block for human immunodeficiency virus-1 capsid assembly. A comparative analysis of the interface dissociation constants between wild-type and two mutant CA proteins, cross-linked hexamer (A14C/E45C/W184A/M185A) and A14C/E45C, yielded results that are consistent with the trimer of dimers with a triangular geometry being the capsomere building block involved in CA polymer growth. 2012 Biochemistry Abstract HIV A14C;E45C;M185A;W184A;A14C;E45C 131;136;147;141;158;163 135;140;152;146;162;167 Capsid;Capsid 96;305 98;307 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. At week 88 F121Y was no longer detected, L74I and T97A were maintained and Y143R emerged. 2012 Antiviral research Abstract HIV L74I;T97A;Y143R 41;50;75 45;54;80 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. Both Stanford Database and Geno2Pheno list F121Y as conferring intermediate resistance "in vitro" both to raltegravir and elvitegravir. 2012 Antiviral research Abstract HIV F121Y 43 48 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. Changing of RAL-containing regimen upon the identification of F121Y might avoid the evolution of raltegravir resistance. 2012 Antiviral research Abstract HIV F121Y 62 67 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. Different resistance mutations in HIV integrase from patients using these antiretroviral drugs have been described and G148H/R/K, N155H and less frequently Y143C/H/R are considered major resistant mutations to raltegravir. 2012 Antiviral research Abstract HIV G148H;G148K;G148R;N155H;Y143C;Y143H;Y143R 119;119;119;130;156;156;156 128;128;128;135;165;165;165 IN 38 47 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. F121Y might be an alternative pathway to Y143R. 2012 Antiviral research Abstract HIV Y143R;F121Y 41;0 46;5 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. The emergence of F121Y was observed at week 32 and 40, alongside with L74I, T97A, Q137H and V151I. 2012 Antiviral research Abstract HIV F121Y;L74I;Q137H;T97A;V151I 17;70;82;76;92 22;74;87;80;97 22564967 In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen. We report for the first time the "in vivo" selection F121Y and evolution to Y143R in a 31years old male clade B HIV-1 infected patient failing a raltegravir-containing salvage regimen. 2012 Antiviral research Abstract HIV F121Y;Y143R 53;76 58;81 HIV infections 112 126 22574920 Energetics of mutation-induced changes in potency of lersivirine against HIV-1 reverse transcriptase. A common problem with the first generation NNRTIs is the emergence of mutations in the HIV-1 reverse transcriptase (RT), in particular, K103N and Y181C, which lead to resistance to the entire class of inhibitor. 2012 The journal of physical chemistry. B Abstract HIV K103N;Y181C 136;146 141;151 RT;NNRTI;RT 93;43;116 114;49;118 22574920 Energetics of mutation-induced changes in potency of lersivirine against HIV-1 reverse transcriptase. For the mutants K103N and Y181C only a moderate (2-fold) increase in the dissociation constant is found, due to a balance of opposite changes in the polar solvation as well as the electrostatic and van der Waals interactions between LRV and RT. 2012 The journal of physical chemistry. B Abstract HIV K103N;Y181C 16;26 21;31 RT 241 243 22574920 Energetics of mutation-induced changes in potency of lersivirine against HIV-1 reverse transcriptase. The dissociation constant is decreased for the Y188C and G190A (2-fold), the M184V (5-fold), and the Y188C/Y188C mutant (10-fold), due to stronger electrostatic interactions between LRV and RT. 2012 The journal of physical chemistry. B Abstract HIV G190A;M184V;Y188C;Y188C;Y188C 57;77;47;107;101 62;82;52;112;106 RT 190 192 22574920 Energetics of mutation-induced changes in potency of lersivirine against HIV-1 reverse transcriptase. The strongest (54-fold) increase in the dissociation constant is found for the mutant F227C, originating from reduced electrostatic and van der Waals interactions between LRV and RT as well as a higher energetic penalty from the desolvation of polar groups. 2012 The journal of physical chemistry. B Abstract HIV F227C 86 91 RT 179 181 22575532 Chiral resolution, absolute configuration assignment and biological activity of racemic diarylpyrimidine CH(OH)-DAPY as potent nonnucleoside HIV-1 reverse transcriptase inhibitors. However, (-)-(S)-3a showed higher potency than (+)-(R)-3a against the double HIV-1 RT mutant (K103N+Y181C) as well as HIV-2 strain ROD. 2012 European journal of medicinal chemistry Abstract HIV K103N;Y181C 94;100 99;105 RT 83 85 22583022 Genetic and functional analysis of HIV type 1 nef gene derived from long-term nonprogressor children: association of attenuated variants with slow progression to pediatric AIDS. The emergence or presence of Nef L58V substitution was associated with viral attenuation, indicated by a reduction in HIV viral loads, a persistent preservation of CD4(+) T cell counts, and lack of AIDS-related symptoms. 2012 AIDS research and human retroviruses Abstract HIV L58V 33 37 Nef 29 32 AIDS 198 202 22585715 Characterization of HIV-1 subtypes and drug resistance mutations among individuals infected with HIV in Georgia. Among patients with no prior exposure to ARVs, mutations associated with resistance were detected in five patients: three (2.4%) patients had reverse transcriptase (RT) inhibitor mutations and two other patients had the protease (PI) inhibitor associated mutation M46I. 2012 Journal of medical virology Abstract HIV M46I 264 268 RT;PR;PI;RT 142;220;230;165 163;228;232;167 22585715 Characterization of HIV-1 subtypes and drug resistance mutations among individuals infected with HIV in Georgia. PI mutation V77I was found in 42 of subtype A isolates. 2012 Journal of medical virology Abstract HIV V77I 12 16 PI 0 2 22585715 Characterization of HIV-1 subtypes and drug resistance mutations among individuals infected with HIV in Georgia. The most common NRTI resistance mutation was M184V/I (74.1%). 2012 Journal of medical virology Abstract HIV M184I;M184V 45;45 52;52 NRTI 16 20 22585715 Characterization of HIV-1 subtypes and drug resistance mutations among individuals infected with HIV in Georgia. With regard to NNRTI mutations, G190S/A was the most frequent mutation, which might be a preferred mutations for subtype A. 2012 Journal of medical virology Abstract HIV G190A;G190S 32;32 39;39 NNRTI 15 20 22587343 Transmitted antiretroviral drug resistance and thumb subdomain polymorphisms among newly HIV type 1 diagnosed patients infected with CRF01_AE and CRF07_BC virus in Guangdong Province, China. Three major resistance mutations, K103N, M184V, and Y188L, each of which caused more than one drug resistance, appeared in only two patients; the prevalence [1.7 % (2/119)] was relatively low. 2012 AIDS research and human retroviruses Abstract HIV K103N;M184V;Y188L 34;41;52 39;46;57 22587343 Transmitted antiretroviral drug resistance and thumb subdomain polymorphisms among newly HIV type 1 diagnosed patients infected with CRF01_AE and CRF07_BC virus in Guangdong Province, China. Until now, this is the first observation of the five newly identified accessory mutations, V35T, K43E, V60I, K122E, and E203D, and seven thumb subdomain polymorphisms, A272P, K277R, K281R, T286A, E291D, V292I, and I293V, in the RT gene in China. 2012 AIDS research and human retroviruses Abstract HIV A272P;E203D;E291D;I293V;K122E;K277R;K281R;K43E;T286A;V292I;V35T;V60I 168;120;196;214;109;175;182;97;189;203;91;103 173;125;201;219;114;180;187;101;194;208;95;107 RT 228 230 22591854 Design, synthesis, anti-HIV evaluation and molecular modeling of piperidine-linked amino-triazine derivatives as potent non-nucleoside reverse transcriptase inhibitors. Screening results indicated that most compounds showed excellent activity against wild-type HIV-1 with EC(50) values in low nanomolar concentration range (especially compound 6b3, EC(50) = 4.61 nM, SI = 5945) and high activity against K103N/Y181C resistant mutant strain of HIV-1 with EC(50) values in low micromolar concentration range. 2012 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 235;241 240;246 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. K103N/S prevalence increased from 1.9% to 8.0% between 1995 and 2010 (P(trend) = 0.04). 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;K103S 0;0 7;7 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. M41L (3.7%), T215Y (4.0%), and K103N/S (4.7%) were the most common mutations. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;K103S;T215Y;M41L 31;31;13;0 38;38;18;4 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. M184V and L63P were the dominant mutations for the reverse transcriptase and the protease genes, respectively, but an increase in the incidence of minority mutations was observed. 2012 AIDS research and treatment Abstract HIV L63P;M184V 10;0 14;5 RT;PR 51;81 72;89 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. Compound 5 was threefold more efficiently incorporated compared to TFV-DP with RT(K65R). 2012 Bioorganic & medicinal chemistry letters Abstract HIV K65R 82 86 RT 79 81 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. The kinetics of incorporation for 5 using the drug resistant mutant enzyme K65R was also determined. 2012 Bioorganic & medicinal chemistry letters Abstract HIV K65R 75 79 22606344 Association of enhanced HIV-1 neutralization by a single Y681H substitution in gp41 with increased gp120-CD4 interaction and macrophage infectivity. In summary, our data indicate that Y681H substitution exposes neutralizing epitopes in CD4bs and MPER towards comprehensive interference in HIV-1 entry. 2012 PloS one Abstract HIV Y681H 35 40 22613387 [Study on HIV-1 drug resistance profile of 257 AIDS patients with failure on the first-line antiretroviral treatment in Henan]. 26.46% of the samples had M184V/I mutation which was the highest NRTIs mutation among the 257 patients. 2012 Zhonghua liu xing bing xue za zhi Abstract HIV M184I;M184V 26;26 33;33 NRTI 65 70 22613387 [Study on HIV-1 drug resistance profile of 257 AIDS patients with failure on the first-line antiretroviral treatment in Henan]. 31.13% of 257 patients appeared most NNRTIs mutation K103N in this study, with the prevalence rates also significant different (chi2=14.213, P=0.001) in the three areas. 2012 Zhonghua liu xing bing xue za zhi Abstract HIV K103N 53 58 NNRTI 37 43 22613387 [Study on HIV-1 drug resistance profile of 257 AIDS patients with failure on the first-line antiretroviral treatment in Henan]. 40.47% of the samples harbored>=1 TAM, with T215Y/F having the most, as 33.85%. 2012 Zhonghua liu xing bing xue za zhi Abstract HIV T215F;T215Y 44;44 51;51 22613387 [Study on HIV-1 drug resistance profile of 257 AIDS patients with failure on the first-line antiretroviral treatment in Henan]. Two PIs mutations were detected in 257 patients: M46I/L, (1.17%) and V82F (0.39%). 2012 Zhonghua liu xing bing xue za zhi Abstract HIV M46I;M46L;V82F 49;49;69 55;55;73 PI 4 7 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. 18 isolates from naive patients and dilutions of a control K65R plasmid were analysed by Sanger plus UDPS. 2012 PloS one Abstract HIV K65R 59 63 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. BACKGROUND: We and others have shown that subtype C HIV-1 isolates from patients failing on a regimen containing stavudine (d4T) or zidovudine (AZT) exhibit thymidine-associated mutations (TAMs) and K65R which can impair the efficacy of Tenofovir (TDF) at second line. 2012 PloS one Abstract HIV K65R 199 203 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. CONCLUSIONS: While Sanger sequencing of subtype C isolates from treated patients at failure of d4T or AZT plus 3TC plus NVP or EFV exhibited numerous mutations including TAMs and 8% K65R, UDPS quantitation of K65R variants in the same series did not provide any more information than Sanger. 2012 PloS one Abstract HIV K65R;K65R 182;209 186;213 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Depending on the various studies, the prevalence of K65R substitution as determined by the Sanger method ranges from 4 to 30%. 2012 PloS one Abstract HIV K65R 52 56 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Other samples without K65R by Sanger exhibited quantities of K65R variants ranging from <0.4% to 0.80%, which were below the values observed in isolates from naive patients. 2012 PloS one Abstract HIV K65R;K65R 22;61 26;65 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Our aim was to determine whether ultra-deep pyrosequencing (UDPS) could provide more information than the Sanger method about selection of K65R in this population of patients. 2012 PloS one Abstract HIV K65R 139 143 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Quantitation of K65R variants by UDPS ranged from <0.4% to 3.08%. 2012 PloS one Abstract HIV K65R 16 20 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Sanger sequences of viral isolates from patients at failure of d4T or AZT plus 3TC plus NVP or EFV showed numerous DRMs to nucleoside reverse transcriptase inhibitors (NRTIs) including M184V, thymidine-associated mutations (TAMs) plus DRMs to non- nucleoside reverse transcriptase inhibitors (NNRTIs). 2012 PloS one Abstract HIV M184V 185 190 NRTI;NRTI;NNRTI;NRTI 123;248;293;168 155;280;299;173 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Two K65R were observed by Sanger in this series of 27 samples with UDPS percentages of 27 and 87%. 2012 PloS one Abstract HIV K65R 4 8 22616647 Low drug resistance levels among drug-naive individuals with recent HIV type 1 infection in a rural clinical cohort in southwestern Uganda. One participant (1.4%, 95% CI: 0.04-7.5%) had two nonnucleoside reverse transcriptase inhibitor mutations (G190E and P225H). 2012 AIDS research and human retroviruses Abstract HIV G190E;P225H 107;117 113;122 NNRTI 50 85 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. Additional studies are warranted to characterize the effects of N348I on virologic response to second- and third-line regimens in resource-limited settings where subtype C predominates. 2012 Clinical infectious diseases Abstract HIV N348I 64 69 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. CONCLUSIONS: N348I emerges frequently with virologic failure of first-line ART in subtype C HIV-1 infection and reduces susceptibility to NVP, EFV, ETV, and AZT. 2012 Clinical infectious diseases Abstract HIV N348I 13 18 HIV infections 92 107 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. N348I emerged at the same time, or after, M184V. 2012 Clinical infectious diseases Abstract HIV M184V;N348I 42;0 47;5 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. N348I in the context of polymerase domain mutations reduced susceptibility to NVP (8.9-13-fold), EFV (4-56-fold), etravirine (ETV; 1.9-4.7-fold) and decreased hypersusceptibility to zidovudine (AZT; 1.4-2.2-fold). 2012 Clinical infectious diseases Abstract HIV N348I 0 5 Pol 24 34 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. N348I in the RT connection domain emerged in 45% (P = .002) and 12% (P = .06) of participants receiving failing regimens containing NVP or EFV, respectively. 2012 Clinical infectious diseases Abstract HIV N348I 0 5 RT 13 15 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. Recombinant viruses containing full-length plasma-derived RT sequences from participants with N348I at virologic failure were assayed for drug susceptibility. 2012 Clinical infectious diseases Abstract HIV N348I 94 99 RT 58 60 22618567 Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors. RESULTS: Y181C and M184V mutations in the RT polymerase domain were associated with failure of stavudine-lamivudine-nevirapine (d4T/3TC/NVP; P < .01), and K103N, V106M, and M184V with failure of d4T/3TC/efavirenz (EFV; P < .01). 2012 Clinical infectious diseases Abstract HIV K103N;M184V;M184V;V106M;Y181C 155;19;173;162;9 160;24;178;167;14 Pol;RT 45;42 55;44 22623801 Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. M184I/V and E138K are signature mutations of clinical relevance in HIV-1 reverse transcriptase (RT) for the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (3TC) and emtricitabine (FTC) and the second-generation (new) nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV), respectively, and the E138K mutation has also been shown to be selected by etravirine in cell culture. 2012 Journal of virology Abstract HIV E138K;E138K;M184I;M184V 12;328;0;0 17;333;7;7 NNRTI;NRTI;RT;NNRTI;NRTI;RT 233;108;73;280;153;96 268;140;94;285;158;98 22623801 Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. The E138K mutation was recently shown to compensate for the low enzyme processivity and viral fitness associated with the M184I/V mutations through enhanced deoxynucleoside triphosphate (dNTP) usage, while the M184I/V mutations compensated for defects in polymerization rates associated with the E138K mutations under conditions of high dNTP concentrations. 2012 Journal of virology Abstract HIV E138K;E138K;M184I;M184I;M184V;M184V 4;296;122;210;122;210 9;301;129;217;129;217 22623801 Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. The M184I mutation was also shown to enhance resistance to RPV and ETR when present together with the E138K mutation. 2012 Journal of virology Abstract HIV E138K;M184I 102;4 107;9 22623801 Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. Through experiments in which E138K-containing viruses were selected with 3TC-FTC and in which M184I/V viruses were selected with ETR, we demonstrated that ETR was able to select for the E138K mutation in viruses containing the M184I/V mutations and that the M184I/V mutations consistently emerged when E138K viruses were selected with 3TC-FTC. 2012 Journal of virology Abstract HIV E138K;E138K;E138K;M184I;M184I;M184I;M184V;M184V;M184V 29;186;302;94;227;258;94;227;258 34;191;307;101;234;265;101;234;265 22623801 Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. We also performed biochemical subunit-selective mutational analyses to investigate the impact of the E138K mutation on RT function and interactions with the M184I mutation. 2012 Journal of virology Abstract HIV E138K;M184I 101;157 106;162 RT 119 121 22623801 Subunit-selective mutational analysis and tissue culture evaluations of the interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase. We now show that the E138K mutation decreased rates of polymerization, impaired RNase H activity, and conferred ETR resistance through the p51 subunit of RT, while an enhancement of dNTP usage as a result of the simultaneous presence of both mutations E138K and M184I occurred via both subunits. 2012 Journal of virology Abstract HIV E138K;E138K;M184I 21;252;262 26;257;267 RT 154 156 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. Computational analysis including modeling of wild-type HIV-1 Nef and V66A Nef SMR mutant using structural homology and molecular dynamics of ligand-associated interactions indicated significant structural changes in the Nef mutant, thus supporting the importance of the SMR domain for mediating Nef vesicle secretion. 2012 Journal of molecular modeling Abstract HIV V66A 69 73 Nef;Nef;Nef;Nef 61;74;220;295 64;77;223;298 22648883 HIV-1 drug resistance at virological failure versus immunological failure among patients failing first-line antiretroviral therapy in a resource-limited setting. Q151M, a multidrug RAM, was more commonly observed in the IF group (14.8% versus 2.9%, P = 0.032). 2012 International journal of STD & AIDS Abstract HIV Q151M 0 5 22648883 HIV-1 drug resistance at virological failure versus immunological failure among patients failing first-line antiretroviral therapy in a resource-limited setting. Using IF to diagnose treatment failure is associated with higher HIV-1 RNA levels and a higher rate of Q151M, which can limit the options for second-line ART. 2012 International journal of STD & AIDS Abstract HIV Q151M 103 108 22659320 Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor. We show that a single-chain Fv fragment (scFv) of a previously reported monoclonal antibody (mAb1696), which recognizes the N-terminus of PR, dissociates a dimeric mature D25N PR mutant with an enhanced dimer dissociation constant (K(d)) in the sub-micromolar range to form predominantly a monomer-scFv complex at a 1:1 ratio, along with small (5-10%) amounts of a dimer-scFv complex. 2012 Journal of molecular biology Abstract HIV D25N 171 175 PR;PR 138;176 140;178 22695298 E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure. Additionally, analysis of 601 patients PBMCs sequences revealed that the copresence of mutations E138K and M184I were never detected in nonhypermutated sequences, whereas these mutations were found at a high frequency (24%) in the context of APOBEC3 editing and in the absence of exposure to etravirine-rilpivirine. 2012 AIDS (London, England) Abstract HIV E138K;M184I 97;107 102;112 22695298 E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure. BACKGROUND: Recent clinical trials with rilpivirine combined with emtricitabine and tenofovir revealed that patients failing treatment, frequently, harbored viruses encoding resistance-associated mutations in the HIV-1 reverse transcriptase at position E138K and M184I. 2012 AIDS (London, England) Abstract HIV E138K;M184I 253;263 258;268 RT 219 240 22695298 E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure. CONCLUSION: We demonstrate using in-vitro experiments and analyzing patients PBMCs sequences that M184I and E138K resistance-associated mutations may pre-exist in proviral reservoir at a high frequency prior to drug exposure, as a result of APOBEC3 editing. 2012 AIDS (London, England) Abstract HIV E138K;M184I 108;98 113;103 22695298 E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure. RESULTS: In-vitro replication experiments in cell lines with and without APOBEC3 expression suggest that APOBEC3-driven mutagenesis contributes to the generation of both M184I and E138K within HIV proviral repository in the absence of drug exposure. 2012 AIDS (London, England) Abstract HIV E138K;M184I 180;170 185;175 22697610 Prevalence of drug-resistant HIV type 1 at the time of initiation of antiretroviral therapy in Portland, Oregon. Predominant RT mutations included M41L, T215C or S, and K103N. 2013 AIDS research and human retroviruses Abstract HIV K103N;M41L;T215C 56;34;40 61;38;45 RT 12 14 22712652 New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors. In particular, compound 9 was uniformly effective against the mutant Y181C, Y188L, and K103N HIV-1 strains; it was highly active against the multidrug resistant mutant IRLL98 HIV-1 strain bearing the K101Q, Y181C, and G190A mutations conferring resistance to NVP, DLV, and EFV and several HIV-1 clades A in PBMC. 2012 Journal of medicinal chemistry Abstract HIV G190A;K101Q;K103N;Y181C;Y181C;Y188L 218;200;87;69;207;76 223;205;92;74;212;81 22713337 Response of simian immunodeficiency virus to the novel nucleoside reverse transcriptase inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine in vitro and in vivo. Although the rebound virus contained the M184V/I mutation in the viral reverse transcriptase, EFdA was fully effective in maintaining suppression of mutant virus throughout the drug treatment period. 2012 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V 41;41 48;48 RT 71 92 22716105 Prevalence of HIV drug resistance mutation in the northern Indian population after failure of the first line antiretroviral therapy. NRTI and NNRTI DRMs were each seen in 115/128 (89.8%) patients, with M184V, M41L, D67N and T215Y being the most frequent among NRTI associated mutations, and K103N, G190A, Y181C and A98G among NNRTI associated ones. 2012 Current HIV research Abstract HIV A98G;D67N;G190A;K103N;M184V;M41L;T215Y;Y181C 182;82;165;158;69;76;91;172 186;86;170;163;74;80;96;177 NNRTI;NNRTI;NRTI;NRTI 9;193;0;127 14;198;4;131 22716105 Prevalence of HIV drug resistance mutation in the northern Indian population after failure of the first line antiretroviral therapy. PI DRMs were observed in 14/128 (10.9%) patients, with L10I, V82A and L89V being the commonest. 2012 Current HIV research Abstract HIV L10I;L89V;V82A 55;70;61 59;74;65 PI 0 2 22716970 Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naive and pretreated patients. As L101I and T124A do not appear to exert any major effect in vivo and double and triple mutants resistant to DTG are infrequently selected by RTG, DTG can be effectively used in INI-naive patients and may retain activity in many patients failing RTG. 2012 Clinical microbiology and infection Abstract HIV L101I;T124A 3;13 8;18 IN 179 182 22716970 Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naive and pretreated patients. Of the mutations selected by DTG in vitro, S153FY was not detected in any isolate while L101I and T124A were highly prevalent in both groups and significantly associated with non-B subtype. 2012 Clinical microbiology and infection Abstract HIV L101I;S153F;S153Y;T124A 88;43;43;98 93;49;49;103 22716970 Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naive and pretreated patients. RTG-selected double and triple mutants, mostly the G140S/Q148H variant, were detected in only 32 (26.7%) RTG-treated patients. 2012 Clinical microbiology and infection Abstract HIV G140S;Q148H 51;57 56;62 22729198 Assessing subtypes and drug resistance mutations among HIV-1 infected children who failed antiretroviral therapy in Kelantan, Malaysia. The most prevalent RT mutations were T215F/V/Y (66.7%), D67G/N (55.6%), K219Q/E/R (44.4%), M184V/I (38.9%), K70R/E (27.8%) and M41L (27.8%), associated with nucleoside reverse transcriptase inhibitors (NRTI) resistance; and K103N (55.6%), G190A (33.3%), and K101P/E/H (27.8%) associated with non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance. 2012 The Brazilian journal of infectious diseases Abstract HIV D67G;D67N;G190A;K101E;K101H;K101P;K103N;K219E;K219Q;K219R;K70E;K70R;M184I;M184V;M41L;T215F;T215V;T215Y 56;56;239;258;258;258;224;72;72;72;108;108;91;91;127;37;37;37 62;62;244;267;267;267;229;81;81;81;114;114;98;98;131;46;46;46 NNRTI;NRTI;NNRTI;NRTI;RT 292;157;341;202;19 328;189;346;206;21 22733652 Impact of lopinavir/ritonavir use on antiretroviral resistance in recent clinical practice. Mutations in the protease gene significantly selected between baseline and failure were L10V, K20R, L33F, M36I, I47V, I54V, A71V and I85V (P < 0.05). 2012 The Journal of antimicrobial chemotherapy Abstract HIV A71V;I47V;I54V;I85V;K20R;L10V;L33F;M36I 124;112;118;133;94;88;100;106 128;116;122;137;98;92;104;110 PR 17 25 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. CONCLUSION: Preliminary data show very high rates (>65%) of K65R for patients failing TDF-based first-line regimens at McCord Hospital with few additional nucleoside reverse transcriptase inhibitor mutations compared with subtype B. 2012 AIDS (London, England) Abstract HIV K65R 60 64 NRTI 155 187 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. OBJECTIVE: We sought to determine the rate of the K65R mutation in patients receiving tenofovir (TDF)-based antiretroviral therapy (ART) with subtype C HIV infection. 2012 AIDS (London, England) Abstract HIV K65R 50 54 HIV infections 152 165 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Thirty-five (6.0%) of these patients had virologic failure and 23 of 33 (69.7%) of the virologic failure patients had the K65R mutation. 2012 AIDS (London, England) Abstract HIV K65R 122 126 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Two (3.8%) of these patients had virologic failure and one of the virologic failure patients had the K65R mutation. 2012 AIDS (London, England) Abstract HIV K65R 101 105 22761416 HIV-1 reverse transcriptase (RT) polymorphism 172K suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and non-nucleoside RT inhibitors. Q151M complex). 2012 The Journal of biological chemistry Abstract HIV Q151M 0 5 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Precise replacement of the MVA orthologs of C11R, F11L, A44L and B8R with a model antigen positioned to use the same translation initiation codon allowed early transgene expression similar to or slightly greater than that achieved by the commonly-used p7.5 or short synthetic promoters. 2012 PloS one Abstract HIV A44L;C11R;F11L 56;44;50 60;48;54 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. The enhancement in immunogenicity observed using the C11R or F11L promoters compared with p7.5 was similar to that obtained with the mH5 promoter compared with p7.5. 2012 PloS one Abstract HIV C11R;F11L 53;61 57;65 22763565 Risk factors for raltegravir resistance development in clinical practice. Among patients without main resistance mutations, two patients showed raltegravir phenotypic resistance, one naturally with F121Y at baseline and the other acquiring G118R at failure. 2012 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 124;166 129;171 22784038 Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. 2012 The New England journal of medicine Abstract HIV A62V;M184V;K65R 17;6;0 21;11;4 HIV infections 119 138 22789986 Resistance to HIV integrase inhibitors. RECENT FINDINGS: New resistance mutations, such as G118R, R263K and S153Y, have been recently identified through in-vitro selection studies with second-generation integrase strand-transfer inhibitors (INSTIs). 2012 Current opinion in HIV and AIDS Abstract HIV G118R;R263K;S153Y 51;58;68 56;63;73 IN;INSTI 163;201 172;207 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. BACKGROUND: We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus replication for years. 2012 Retrovirology Abstract HIV K65R 251 255 RT 268 289 22807446 Characterization of a proteasome and TAP-independent presentation of intracellular epitopes by HLA-B27 molecules. Assuming that such difference could be due to the unpaired, highly reactive Cys-67 distinguishing the HLA-B27 molecules, C67S mutants in HLA-B*2705 and B*2709 and V67C mutant in HLA-A*0201 were also analyzed. 2012 The Journal of biological chemistry Abstract HIV C67S;V67C 121;163 125;167 22807446 Characterization of a proteasome and TAP-independent presentation of intracellular epitopes by HLA-B27 molecules. Here, using these chimeric proteins as epitope suppliers, we compared with each other and with the HLA-A2 molecules, the two HLA-B*2705 and B*2709 alleles differing at residue 116 (D116H) and differentially associated with AS. 2012 The Journal of biological chemistry Abstract HIV D116H 181 186 22807446 Characterization of a proteasome and TAP-independent presentation of intracellular epitopes by HLA-B27 molecules. The data, together with the occurrence on the cell surface of unfolded molecules in the case of C67S-B*2705 mutant but not in that of C67S-B*2709 mutant, indicates that Cys-67 has a more critical role in stabilizing the B*2705 rather than the B*2709 complexes. 2012 The Journal of biological chemistry Abstract HIV C67S;C67S 96;134 100;138 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. A double Phe16Ala/Trp37Ala substitution further reduces the latter activity. 2013 Virus research Abstract HIV F16A;F16W;W37A 9;9;18 17;17;26 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. In contrast, single amino acid substitutions of either Phe16Ala or Trp37Ala significantly slow down NC's DNA interaction kinetics, while retaining some helix-destabilization capability. 2013 Virus research Abstract HIV F16A;W37A 55;67 63;75 NC 100 102 22818969 Minority variants associated with resistance to HIV-1 nonnucleoside reverse transcriptase inhibitors during primary infection. Four samples (15%) had a major rilpivirine resistant mutation (E138G, K101E and E138A), 3 of which were detected by UDPS. 2012 Journal of clinical virology Abstract HIV E138A;E138G;K101E 80;63;70 85;68;75 22818969 Minority variants associated with resistance to HIV-1 nonnucleoside reverse transcriptase inhibitors during primary infection. The 11 RAMs not detected by bulk sequencing were A98G (n=2), L100I (n=3), K101E (n=2), V106I (n=3) and E138G (n=1). 2012 Journal of clinical virology Abstract HIV A98G;E138G;K101E;L100I;V106I 49;103;74;61;87 53;108;79;66;92 22823755 Transmitted antiretroviral drug resistance in newly HIV-infected and untreated patients in Segou and Bamako, Mali. There were two (4%) patients with nucleoside reverse transcriptase inhibitor (NRTI) mutations (one M184V and one T215Y), two (4%) with non-NRTI mutations (two K103N), and one (2%) with a protease inhibitor mutation (one I54V). 2013 AIDS research and human retroviruses Abstract HIV I54V;K103N;M184V;T215Y 220;159;99;113 224;164;104;118 NRTI;NNRTI;PR;NRTI 34;135;187;78 66;143;195;82 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. In order to understand the role of the three individual carbohydrate-binding sites (CBS) in GRFT, mutations were made at each site (D30A, D70A, and D112A), and the resulting mutants were investigated. 2012 Molecular pharmaceutics Abstract HIV D112A;D30A;D70A 148;132;138 153;136;142 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. Mutation of any individual CBS on GRFT reduced binding of the protein to mannose, and ELISA assays revealed a partial loss of ability of each GRFT point mutant to bind gp120, with a near-complete loss of binding by the triple mutant D30A/D70A/D112A GRFT. 2012 Molecular pharmaceutics Abstract HIV D112A;D30A;D70A 243;233;238 248;237;242 gp120 168 173 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Detected CD mutations were G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), Y318F (2.1%), G333E (2.1%), and A360V (2.1%). 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A360V;A371V;E399D;G333E;G335D;N348I;V365I;Y318F 130;42;57;112;27;71;85;98 135;47;62;117;32;76;90;103 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. The observed trend toward reduced likelihood of etravirine or nevirapine resistance in the presence of G335D should be investigated further. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G335D 103 108 22837442 Trends in HIV-1 reverse transcriptase resistance-associated mutations and antiretroviral prescription data from 2003-2010. Among samples resembling those typical of first-line NNRTI-based failures, prevalence of K103N increased slightly, but prevalence of M184V/I decreased (49.8% to 36.8%), as did other NRTI RAMs. 2012 Antiviral therapy Abstract HIV K103N;M184I;M184V 89;133;133 94;140;140 NNRTI;NRTI 53;182 58;186 22837442 Trends in HIV-1 reverse transcriptase resistance-associated mutations and antiretroviral prescription data from 2003-2010. Emtricitabine (FTC) or lamivudine (3TC), components of recommended initial ARV regimens, are structurally related and share the same resistance mutation (M184V/I). 2012 Antiviral therapy Abstract HIV M184I;M184V 154;154 161;161 22837442 Trends in HIV-1 reverse transcriptase resistance-associated mutations and antiretroviral prescription data from 2003-2010. However they differ with respect to potency and incidence of M184V/I. 2012 Antiviral therapy Abstract HIV M184I;M184V 61;61 68;68 22837442 Trends in HIV-1 reverse transcriptase resistance-associated mutations and antiretroviral prescription data from 2003-2010. RESULTS: In the unfiltered data set (n=107,231), the prevalence in 2010 decreased compared to 2003 for all nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs, such as M184V/I (44.0% to 17.9%), T215Y (22.7% to 4.1%), and K65R (4.3% to 2.1%). 2012 Antiviral therapy Abstract HIV K65R;M184I;M184V;T215Y 235;182;182;208 239;189;189;213 RT;NRTI 129;162 150;166 22842995 Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies. Conversely, Y181C, Y181I, V106A, H221Y and F227L were more prevalent following NVP than EFV failures. 2013 AIDS (London, England) Abstract HIV F227L;H221Y;V106A;Y181C;Y181I 43;33;26;12;19 48;38;31;17;24 22842995 Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies. E138K/M184I were absent. 2013 AIDS (London, England) Abstract HIV M184I;E138K 6;0 11;5 22842995 Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies. In patients with ETR failure, cross-resistance to RPV was seen in 27.6%, mainly as result of Y181C (81.3%), V179I (43.8%), V90I (31.3%) and V108I (18.8%). 2013 AIDS (London, England) Abstract HIV V108I;V179I;V90I;Y181C 140;108;123;93 145;113;127;98 22842995 Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies. K101E/M184I was seen in 1%. 2013 AIDS (London, England) Abstract HIV M184I;K101E 6;0 11;5 22842995 Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies. Mutations L100I and V108I were significantly more frequent in patients failing EFV than NVP (7.9 vs. 2013 AIDS (London, England) Abstract HIV L100I;V108I 10;20 15;25 22842995 Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies. The prevalence of RPV RAMs was K101E (9.1%), K101P (1.4%), E138A (3.9%), E138G (0.3%), E138K (0.3%), E138Q (0.8%), V179L (0.2%), Y181C (21.8%), Y181I (0.5%), Y181V (0.2%), H221Y (8.3%), F227C (0.1%) and M230L (1.5%). 2013 AIDS (London, England) Abstract HIV E138A;E138G;E138K;E138Q;F227C;H221Y;K101E;K101P;M230L;V179L;Y181C;Y181I;Y181V 59;73;87;101;186;172;31;45;203;115;129;144;158 64;78;92;106;191;177;36;50;208;120;134;149;163 22846173 Therapy failure resulting from superinfection by a drug-resistant HIV variant. Population sequencing and UDPS revealed the presence of a second HIV-1 strain with a Y188L NNRTI resistance mutation in a sample obtained shortly prior to initiation of therapy. 2012 Antiviral therapy Abstract HIV Y188L 85 90 NNRTI 91 96 22856626 Diversity of HIV type 1 and drug resistance mutations among injecting drug users in Kenya. The prevalence of drug resistance was 13.8% (8/58) with detection of nucleoside reverse transcriptase inhibitor (NRTI) mutations, T215F (n=5), K219Q (n=3), M184V (n=1), and nonnucleoside RTI mutation, K103N (n=1). 2013 AIDS research and human retroviruses Abstract HIV K103N;K219Q;M184V;T215F 201;143;156;130 206;148;161;135 NRTI;NRTI;RT 69;113;187 101;117;190 22860571 High rate of antiretroviral drug resistance mutations in HIV type 1-infected Senegalese children in virological failure on first-line treatment according to the World Health Organization guidelines. The NRTI-resistant viruses harbored the M184V/I (95%), Q151M (2%), and thymidine-analogue mutations (40%), and the NNRTI-resistant viruses harbored the K103N (34%), Y181C (32%), G190A (23%), and K101E (21%) mutations. 2013 AIDS research and human retroviruses Abstract HIV G190A;K101E;K103N;M184I;M184V;Q151M;Y181C 178;195;152;40;40;55;165 183;200;157;47;47;60;170 NNRTI;NRTI 115;4 120;8 22870806 Arylazolyl(azinyl)thioacetanilide. Part 9: Synthesis and biological investigation of thiazolylthioacetamides derivatives as a novel class of potential antiviral agents. The results showed that some 2-chloro substituted thiazolylthioacetamide derivatives possessed potent activity against wild type HIV-1 and several key mutant strains (E138K, K103N, L100I) of HIV-1 in MT-4 cells with EC(50) values in micromolar range. 2012 Archives of pharmacal research Abstract HIV E138K;K103N;L100I 167;174;181 172;179;186 22878339 Rilpivirine, a novel non-nucleoside reverse transcriptase inhibitor for the management of HIV-1 infection: a systematic review. E138K is likely to cause cross-resistance to other NNRTIs thereby limiting the further utilization of this class. 2012 Antiviral therapy Abstract HIV E138K 0 5 NNRTI 51 57 22878339 Rilpivirine, a novel non-nucleoside reverse transcriptase inhibitor for the management of HIV-1 infection: a systematic review. The most common mutation that emerged during RPV therapy was E138K, which often occurred in combination with M184I. 2012 Antiviral therapy Abstract HIV E138K;M184I 61;109 66;114 22878423 The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults. The median fold change to dolutegravir for isolates containing changes at G140S + Q148H, G140S + Q148R, T97A + Y143R, and N155H (thus including raltegravir signature resistance codons) were 3.75, 13.3, 1.05, and 1.37, respectively. 2012 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G140S;G140S;N155H;Q148H;Q148R;T97A;Y143R 74;89;122;82;97;104;111 79;94;127;87;102;108;116 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. BACKGROUND: Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. 2012 Retrovirology Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 240;255;255;246;208;202;278;218 244;262;262;250;213;206;283;223 RT;RT 164;187 185;189 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. CONCLUSIONS: Our study shows the association of R284K and TAM1 mutations in individuals failing therapy with tenofovir/emtricitabine, and unveils a novel mechanism by which secondary mutations are selected in the context of drug-resistance mutations. 2012 Retrovirology Abstract HIV R284K 48 53 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. 2012 Retrovirology Abstract HIV M184V;R284K;V118I;V179I 48;58;34;41 53;63;39;46 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. 2012 Retrovirology Abstract HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 28;178;23;173;40;34;184 33;183;27;177;45;39;189 RT;RT 20;190 22;193 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex. 2012 Retrovirology Abstract HIV R284K 45 50 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. R284K) have been identified in association with TAMs. 2012 Retrovirology Abstract HIV R284K 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. RESULTS: The cross-sectional study carried out with > 200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. 2012 Retrovirology Abstract HIV K65R;M184V 223;178 227;183 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. 2012 Retrovirology Abstract HIV R284K 84 89 RT 31 34 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations. 2012 Retrovirology Abstract HIV R284K 194 199 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. 2012 Retrovirology Abstract HIV R284K 51 56 22894923 Interaction of human immunodeficiency virus type 1 Vif with APOBEC3G is not dependent on serine/threonine phosphorylation status. Interestingly, T96E and not T96A was functionally impaired, indicating that this residue is critical for Vif-A3G physical interaction and activity. 2012 The Journal of general virology Abstract HIV T96A;T96E 28;15 32;19 Vif 105 108 22894923 Interaction of human immunodeficiency virus type 1 Vif with APOBEC3G is not dependent on serine/threonine phosphorylation status. Putative serine/threonine phosphorylation point mutations in Vif (T96, S144, S165, T188) using single-round infection assays demonstrated that these mutations did not alter Vif activity, with the exception of Vif.T96E. 2012 The Journal of general virology Abstract HIV T96E 213 217 Vif;Vif;Vif 61;173;209 64;176;212 22900472 Low prevalence of transmitted HIV type 1 drug resistance among antiretroviral-naive adults in a rural HIV clinic in Kenya. Two TDR mutations to nucleoside reverse transcriptase inhibitors [n=1 (T215D)] and protease inhibitors [n=1 (M46L)] were identified, giving an overall TDR prevalence of 1.1% (95% CI: 0.1-3.9). 2013 AIDS research and human retroviruses Abstract HIV M46L;T215D 109;71 113;76 NRTI;PR 21;83 53;91 22906365 The prevalence of transmitted drug resistance in newly diagnosed HIV-infected individuals in Croatia: the role of transmission clusters of men who have sex with men carrying the T215S surveillance drug resistance mutation. A total of 12 transmission pairs and eight distinct transmission clusters were identified with the largest cluster harboring sequences from 19 patients; among them all but two were carrying the T215S mutation. 2013 AIDS research and human retroviruses Abstract HIV T215S 194 199 22906365 The prevalence of transmitted drug resistance in newly diagnosed HIV-infected individuals in Croatia: the role of transmission clusters of men who have sex with men carrying the T215S surveillance drug resistance mutation. The most frequently found NRTI SDRM was T215S (17 of 118 patients, 14.4%). 2013 AIDS research and human retroviruses Abstract HIV T215S 40 45 NRTI 26 30 22909351 Single point mutation induced alterations in the equilibrium structural transitions on the folding landscape of HIV-1 protease. In this background, we report here NMR studies on the effects of D25 N mutation, which removes one negative charge from the protein at the active site, on the equilibrium folding behaviour of PR starting from its acetic acid denatured state. 2013 Journal of biomolecular structure & dynamics Abstract HIV D25N 65 70 PR 192 194 22914581 Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? In three patients tested, the K103N mutation was detected in cellular HIV-1 DNA whereas remaining suppressed on etravirine plus tenofovir/emtricitabine. 2013 AIDS (London, England) Abstract HIV K103N 30 35 22914581 Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? We report long-term virologic response to etravirine and tenofovir/emtricitabine in four HIV-1-infected patients who had prior standard genotypic resistance testing showing an isolated K103N mutation (three acquired, one transmitted). 2013 AIDS (London, England) Abstract HIV K103N 270 275 HIV infections 174 188 22914581 Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation? We report long-term virologic response to etravirine and tenofovir/emtricitabine in four HIV-1-infected patients who had prior standard genotypic resistance testing showing an isolated K103N mutation (three acquired, one transmitted). 2013 AIDS (London, England) Abstract HIV K103N 185 190 HIV infections 89 103 22919750 [Genotyping and variability of HIV-1 in 26 cases of paid blood donors]. M184V, K101E and G190A were detected in the RT region, respectively. 2012 Zhonghua shi yan he lin chuang bing du xue za zhi Abstract HIV G190A;K101E;M184V 17;7;0 22;12;5 RT 44 46 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. The mismatch extension efficiency was reduced for all mutants, with Lys66Ala, Lys66Asn and Lys66Thr showing a four- to six-fold reduction compared with wild-type HIV-1 RT. 2012 The FEBS journal Abstract HIV K66A;K66N;K66T 68;78;91 76;86;99 RT 168 170 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. This hypothesis was tested by steady-state kinetic studies using wild-type HIV-1 RT and four Lys66 substitution mutants: Lys66Arg, Lys66Ala, Lys66Asn and Lys66Thr. 2012 The FEBS journal Abstract HIV K66A;K66N;K66R;K66T 131;141;121;154 139;149;129;162 RT 81 83 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Thus, the Lys66Arg mutant was akin to wild-type HIV-1 RT, whereas all nonconservative mutants displayed significantly decreased efficiency for both events. 2012 The FEBS journal Abstract HIV K66R 10 18 RT 54 56 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. When we tested the mutants for susceptibility to selected nucleoside analog and non-nucleoside analog drugs, similarly to Lys65Arg, the Lys66Ala and Lys66Asn mutants displayed mild resistance to the nucleoside analog drug 3'-azido-3'-deoxythymidine-5'-triphosphate (AZTTP). 2012 The FEBS journal Abstract HIV K65R;K66A;K66N 122;136;149 130;144;157 22933296 Ultrasensitive allele-specific PCR reveals rare preexisting drug-resistant variants and a large replicating virus population in macaques infected with a simian immunodeficiency virus containing human immunodeficiency virus reverse transcriptase. We detected RT inhibitor (RTI) resistance mutations K65R and M184I but not K103N in 2 of 2 RT-SHIV-infected macaques prior to EFV exposure. 2012 Journal of virology Abstract HIV K103N;K65R;M184I 75;52;61 80;56;66 RT;RT;RT 26;12;91 29;14;93 22943210 Emtricitabine/tenofovir in the treatment of HIV infection: current PK/PD evaluation. Furthermore, cytidine analog-associated M184V is less likely to appear with FTC than with lamivudine when both are given with TDF. 2012 Expert opinion on drug metabolism & toxicology Abstract HIV M184V 40 45 22943210 Emtricitabine/tenofovir in the treatment of HIV infection: current PK/PD evaluation. If patients treated with FTC/TDF FDC fail, a lower incidence of TDF-associated K65R resistance mutation seems to develop. 2012 Expert opinion on drug metabolism & toxicology Abstract HIV K65R 79 83 22943898 [Survey of HIV drug resistance threshold in Zhejiang province from 2009 to 2011]. SDRMs for protease inhibitor (PI), nucleotide HIV-reverse transcriptase inhibitor (NRTI) and non-NRTI (NNRTI) (L90M, T215S and Y188L) were all found in one case. 2012 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV L90M;T215S;Y188L 111;117;127 115;122;132 RT;NNRTI;PR;NNRTI;NRTI;PI 50;93;10;103;83;30 71;101;18;108;87;32 22951490 Pre-existing mutations in the rilpivirine Phase III trials ECHO and THRIVE: prevalence and impact on virological response. The presence of allowed NNRTI RAMs was associated with comparable response rates to the overall population (RPV 84.3% versus EFV 82.3%, intent-to-treat time-to-loss-of-virological-response): V90I (82.4% and 100% for RPV and EFV, respectively), V106I (85.7% and 93.3%), V179I (87.7% and 94.0%) and V189I (100.0% and 88.9%). 2013 Antiviral therapy Abstract HIV V106I;V179I;V189I;V90I 244;269;297;191 249;274;302;195 NNRTI 24 29 22955279 Biochemical mechanism of HIV-1 resistance to rilpivirine. Quantum mechanics/molecular mechanics hybrid molecular modeling revealed that p51(E138K) affects access to the RPV binding site by disrupting the salt bridge between p51(E138) and p66(K101). 2012 The Journal of biological chemistry Abstract HIV E138K 82 87 22955279 Biochemical mechanism of HIV-1 resistance to rilpivirine. Virological failure during therapy with RPV and emtricitabine is associated with the appearance of E138K and M184I mutations in RT. 2012 The Journal of biological chemistry Abstract HIV E138K;M184I 99;109 104;114 RT 128 130 22955279 Biochemical mechanism of HIV-1 resistance to rilpivirine. We compared WT with four subunit-specific RT mutants, p66(M184I)/p51(WT), p66(E138K)/p51(E138K), p66(E138K/M184I)/p51(E138K), and p66(M184I)/p51(E138K). 2012 The Journal of biological chemistry Abstract HIV E138K;M184I;E138K;E138K;M184I;M184I;E138K 101;107;78;145;58;134;102 106;112;83;150;63;139;106 RT 42 44 22959895 Feglymycin, a unique natural bacterial antibiotic peptide, inhibits HIV entry by targeting the viral envelope protein gp120. In vitro generated FGM-resistant HIV-1 IIIB virus (HIV-1 IIIB(FGMres)) showed two unique mutations in gp120 at positions I153L and K457I. 2012 Virology Abstract HIV I153L;K457I 121;131 126;136 gp120 102 107 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. Structures of wild-type protease and two mutants (PR(V32I) and PR(I47V)) with V32I and I47V substitutions, which are common in drug resistance, reveal the gem-diol tetrahedral intermediate, the separating N- and C-terminal products, and the C-terminal product of an autoproteolytic peptide. 2012 Biochemistry Abstract HIV I47V;I47V;V32I;V32I 66;87;53;78 70;91;57;82 PR;PR;PR 24;50;63 32;52;65 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. The complex of mutant PR(V32I) with a single C-terminal product shows density for water molecules in the other half of the binding site, including a partial occupancy water molecule interacting with the product carboxylate end and the carbonyl oxygen of one conformation of Gly27, which suggests a potential role of Gly27 in recycling from the product complex to the ligand-free enzyme. 2012 Biochemistry Abstract HIV V32I 25 29 PR 22 24 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. The two products in the complex with mutant PR(I47V) have a 2.2 A separation of the amide and carboxyl carbon of the adjacent ends, suggesting partial cleavage prior to product release. 2012 Biochemistry Abstract HIV I47V 47 51 PR 44 46 22966822 Low prevalence of antiretroviral resistance among HIV type 1-positive prisoners in the Southeast United States. The three most prevalent mutations were K103N 15.8% (12.0, 20.2), M184V 14.3% (10.7,18.5), and M41L 4.9% (2.8,7.8). 2013 AIDS research and human retroviruses Abstract HIV K103N;M184V;M41L 40;66;95 45;71;99 22977160 Mutations selected in HIV-2-infected patients failing a regimen including atazanavir. Besides I50L, four PR mutations previously associated with protease inhibitor resistance (I54L, I64V, V71I and I82F) and six PR mutations of unknown impact (V10I, E37D, S43T, K45R, I75V and F85L) in HIV-2 were also identified in this small group of patients. 2013 The Journal of antimicrobial chemotherapy Abstract HIV E37D;F85L;I50L;I54L;I64V;I75V;I82F;K45R;S43T;V10I;V71I 163;190;8;90;96;181;111;175;169;157;102 167;194;12;94;100;185;115;179;173;161;106 PR;PR;PR 59;19;125 67;21;127 22977160 Mutations selected in HIV-2-infected patients failing a regimen including atazanavir. CONCLUSIONS: Several mutations were associated with virological failure of a regimen including atazanavir/ritonavir in HIV-2-infected patients, including I50L for the first time. 2013 The Journal of antimicrobial chemotherapy Abstract HIV I50L 154 158 22977160 Mutations selected in HIV-2-infected patients failing a regimen including atazanavir. RESULTS: The I50L mutation emerged in 4 out of 28 HIV-2-infected patients failing a HAART regimen including atazanavir/ritonavir. 2013 The Journal of antimicrobial chemotherapy Abstract HIV I50L 13 17 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. A total of seven previously reported mutations (A98G, V106M, V108I, I135T, Y181C, V189I, K238N) and seven novel mutations (P4H, T48I, I178M, V314A, I382L/V, T386A) in the reverse transcriptase gene were found in these NVP-selected mutants. 2012 PloS one Abstract HIV A98G;I135T;I178M;I382L;I382V;K238N;P4H;T386A;T48I;V106M;V108I;V189I;V314A;Y181C 48;68;134;148;148;89;123;157;128;54;61;82;141;75 52;73;139;155;155;94;126;162;132;59;66;87;146;80 RT 171 192 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Among them, V106M and Y181C reduce NVP susceptibility for more than 20-fold, while the other mutations cause less than 20 folds drug resistance. 2012 PloS one Abstract HIV V106M;Y181C 12;22 17;27 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Four combination profiles of mutations were identified in the NVP-selected mutants, which were initiated with A98G, V108I, Y181C and I135T/I382L and followed by more than two other mutations at the end of the selections, respectively. 2012 PloS one Abstract HIV A98G;I135T;I382L;V108I;Y181C 110;133;139;116;123 114;138;144;121;128 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Phenotypic analysis in the NVP-selected mutants showed that all the mutations, except P4H, contribute to NVP resistance. 2012 PloS one Abstract HIV P4H 86 89 22985307 Transmitted HIV type 1 drug resistance in newly diagnosed Cuban patients. In the region of the reverse transcriptase, the most common mutations were K103N and M184V, while in the region of the protease they were L33F and M46L. 2013 AIDS research and human retroviruses Abstract HIV K103N;L33F;M184V;M46L 75;138;85;147 80;142;90;151 RT;PR 21;119 42;127 22989757 The development of novel HIV integrase inhibitors and the problem of drug resistance. Several newly identified resistance mutations, such as G118R, R263K and S153Y, have been identified through tissue culture selection studies with second-generation integrase strand-transfer inhibitors (INSTIs). 2012 Current opinion in virology Abstract HIV G118R;R263K;S153Y 55;62;72 60;67;77 IN;INSTI 164;202 173;208 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. Accordingly, we performed tissue culture studies to investigate the evolutionary dynamics of E138K in both a wild-type (WT) and a Y181C background. 2012 Journal of virology Abstract HIV E138K;Y181C 93;130 98;135 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. However, E138K can be consistently selected by ETR when wild-type viruses but not viruses containing Y181C are grown in tissue culture. 2012 Journal of virology Abstract HIV E138K;Y181C 9;101 14;106 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. The addition of E138K to Y181C also decreased the level of resistance to ETR compared to that obtained with Y181C alone. 2012 Journal of virology Abstract HIV E138K;Y181C;Y181C 16;25;108 21;30;113 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. This study was carried out to evaluate any possible mechanisms that might explain antagonism between the Y181C and E138K mutations. 2012 Journal of virology Abstract HIV E138K;Y181C 115;105 120;110 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. We also generated recombinant enzymes containing Y181C and E138K alone or in combination in order to study enzyme processivity, rates of processive DNA synthesis, enzyme kinetics, and susceptibility to ETR. 2012 Journal of virology Abstract HIV E138K;Y181C 59;49 64;54 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. We now show that the presence of the Y181C mutation prevented the emergence of E138K in cell culture and that the simultaneous presence of E138K and Y181C impaired each of enzyme activity, processivity, rate of processive DNA synthesis, and deoxynucleoside triphosphate (dNTP) affinity. 2012 Journal of virology Abstract HIV E138K;E138K;Y181C;Y181C 79;139;37;149 84;144;42;154 22993165 Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1 reverse transcriptase. Y181C and E138K in HIV-1 RT are among 20 different drug resistance mutations associated with ETR. 2012 Journal of virology Abstract HIV E138K;Y181C 10;0 15;5 RT 25 27 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. Because the emergence of RAL resistance is usually initiated by the N155H mutant, we assessed the role of minor N155H-mutated variants in circulating RNA and archived DNA in five heavily treated patients experiencing long-term RAL therapy failure and harbouring three different resistance profiles determined by standard genotyping. 2013 HIV medicine Abstract HIV N155H;N155H 68;112 73;117 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. CONCLUSIONS: The N155H mutation present at various levels from minority to majority showed no relationship with the three RAL-associated resistance profiles, suggesting that this mutant may not play a role in determining different resistance profiles. 2013 HIV medicine Abstract HIV N155H 17 22 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. During RAL failure, the mutation N155H was detected at different levels in three patients displaying the N155H pathway and gradually declined when the double mutant Q148H+G140S was selected in one patient. 2013 HIV medicine Abstract HIV G140S;N155H;N155H;Q148H 171;33;105;165 176;38;110;170 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. In two patients with the Q148H resistance pathway, no N155H variant was identified by AS-PCR in either viral RNA or DNA. 2013 HIV medicine Abstract HIV N155H;Q148H 54;25 59;30 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. METHODS: Allele-specific polymerase chain reaction (AS-PCR) was used to detect N155H mutants in longitudinal stored plasma and whole-blood samples before, during and after RAL-based regimens in five patients infected with the HIV-1 B subtype. 2013 HIV medicine Abstract HIV N155H 79 84 Pol 25 35 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. Moreover, pre-existing N155H is very infrequent and, if selected during RAL failure, the N155H mutant disappears quickly after RAL withdrawal. 2013 HIV medicine Abstract HIV N155H;N155H 23;89 28;94 22994529 Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens. RESULTS: No minor N155H-mutated variant was found by AS-PCR in either plasma or whole-blood samples collected at baseline and after RAL withdrawal in any of the five patients. 2013 HIV medicine Abstract HIV N155H 18 23 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Two mutations, D474A and T257A, caused large-scale loss of KR21 binding, as well as losses in both CD4/17b and viral inhibition by KR21. 2013 Proteins Abstract HIV D474A;T257A 15;25 20;30 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. (1) The presence of low-dose (1 muM) 3TC prevented reversal to wild-type from an M184V mutant background. 2012 Viruses Abstract HIV M184V 81 86 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Because M184V mutant HIV-1 seems hypersusceptible to adefovir (ADV), we also tested the effect of ADV pressure on the same isolates. 2012 Viruses Abstract HIV M184V 8 13 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. When HIV-1 is exposed to lamivudine (3TC) at inhibitory concentrations, resistant variants carrying the reverse transcriptase (RT) substitution M184V emerge rapidly. 2012 Viruses Abstract HIV M184V 144 149 RT;RT 104;127 125;129 23012977 [Analysis of the polymorphism of the genome region of HIV-1 encoding the fusion protein]. It was also found that high frequency of accessory mutations N126K and E137K were observed in the HR2 region (27.5%). 2012 Voprosy virusologii Abstract HIV E137K;N126K 71;61 76;66 23015721 Intersubtype differences in the effect of a rare p24 gag mutation on HIV-1 replicative fitness. However, whereas in subtype C downstream compensatory mutations at p24(Gag) codons 252 and 260 reduce the adverse effects of M250I, fitness costs in subtype B appear difficult to restore. 2012 Journal of virology Abstract HIV M250I 125 130 p24;Gag 67;71 70;74 23015721 Intersubtype differences in the effect of a rare p24 gag mutation on HIV-1 replicative fitness. In HIV-1 subtype B, the p24(Gag) M250I mutation is a rare variant (0.6%) that is enriched among elite controllers (7.2%) (P = 0.0005) and appears to be a rare escape variant selected by HLA-B58 supertype alleles (P < 0.01). 2012 Journal of virology Abstract HIV M250I 31 38 p24;Gag 24;28 27;31 23015721 Intersubtype differences in the effect of a rare p24 gag mutation on HIV-1 replicative fitness. Indeed, patient-derived subtype B sequences harboring M250I exhibited in vitro replicative defects, while those from subtype C did not. 2012 Journal of virology Abstract HIV M250I 54 59 23015721 Intersubtype differences in the effect of a rare p24 gag mutation on HIV-1 replicative fitness. The structural implications of M250I were predicted by protein modeling to be greater in subtype B versus C, providing a potential explanation for its lower frequency and enhanced replicative defects in subtype B. 2012 Journal of virology Abstract HIV M250I 31 36 23015721 Intersubtype differences in the effect of a rare p24 gag mutation on HIV-1 replicative fitness. Using site-directed mutant viruses, we demonstrate that M250I reduces in vitro viral replicative capacity in both subtype B and subtype C sequences. 2012 Journal of virology Abstract HIV M250I 56 61 23015723 Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1. HIV(11MIX)(P10) contained various amino acid substitutions, including I54V and V82T. 2012 Journal of virology Abstract HIV I54V;V82T 70;79 74;83 23015723 Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1. However, the introduction of I54V/V82T into cHIV(B) (cHIV(B)(I54V/V82T)) compromised TPV's dimerization inhibition and cHIV(B)(I54V/V82T) proved to be significantly TPV resistant. 2012 Journal of virology Abstract HIV I54V;I54V;I54V;V82T;V82T;V82T 127;61;29;34;132;66 131;65;33;38;136;70 23015723 Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1. L24M was responsible for TPV resistance with the cHIV(C) genetic background. 2012 Journal of virology Abstract HIV L24M 0 4 23015723 Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1. The introduction of I54V/V82T into wild-type cHIV(NL4-3) (cHIV(NL4-3(I54V/V82T))) did not block TPV's dimerization inhibition or confer TPV resistance. 2012 Journal of virology Abstract HIV I54V;I54V;V82T;V82T 69;20;25;74 73;24;29;78 23015723 Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1. The introduction of L24M into cHIV(NL4-3) (cHIV(NL4-3(L24M))) interfered with TPV's dimerization inhibition, while L24M increased HIV-1's susceptibility to TPV with the HIV(NL4-3) genetic background. 2012 Journal of virology Abstract HIV L24M;L24M;L24M 20;115;54 24;119;58 23015723 Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1. When selected with TPV, cHIV(NL4-3(I54V/V82T)) most readily developed TPV resistance and acquired E34D, which compromised TPV's dimerization inhibition with the HIV(NL4-3) genetic background. 2012 Journal of virology Abstract HIV I54V;E34D;V82T 35;98;40 39;102;44 23018441 Impact of gag genetic determinants on virological outcome to boosted lopinavir-containing regimen in HIV-2-infected patients. A430V (NC/p1) and I82F (protease-coding region) were associated with virological failure (P = 0.046, P = 0.050, respectively). 2013 AIDS (London, England) Abstract HIV I82F;A430V 18;0 22;5 PR;NC 24;7 32;9 23018441 Impact of gag genetic determinants on virological outcome to boosted lopinavir-containing regimen in HIV-2-infected patients. In protease inhibitor-experienced patients, D427E (NC/p1) was associated with virological response (P = 0.014). 2013 AIDS (London, England) Abstract HIV D427E 44 49 PR;NC 3;51 11;53 23018441 Impact of gag genetic determinants on virological outcome to boosted lopinavir-containing regimen in HIV-2-infected patients. In protease inhibitor-naive patients, T435A (NC/p6), V447M (p1/p6), and Y14H (protease-coding region) were associated with virological failure (P = 0.011, P = 0.033, P = 0.022, respectively). 2013 AIDS (London, England) Abstract HIV T435A;V447M;Y14H 38;53;72 43;58;76 PR;PR;NC;Gag;Gag 3;78;45;48;63 11;86;47;50;65 23018441 Impact of gag genetic determinants on virological outcome to boosted lopinavir-containing regimen in HIV-2-infected patients. T435A and V447M were associated with Y14H (P = 0.018, P = 0.039, respectively). 2013 AIDS (London, England) Abstract HIV V447M;Y14H;T435A 10;37;0 15;41;5 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. A large majority of observed K65R cases were explained by the use of tenofovir, reflecting its wide use in clinical practice. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 29 33 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. Although recent HIV-1 treatment guidelines discouraging these combinations resulted in reduced K65R selection with tenofovir, updated information on the impact of currently recommended regimens on the population selection rate of K65R is presently lacking. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R;K65R 95;230 99;234 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. DISCUSSION: Our finding of a stable time trend of K65R despite elevated use of tenofovir illustrates increased potency of current HIV-1 therapy including tenofovir. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 50 54 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. For any given dual NRTI combination including tenofovir, higher selection rates of K65R were consistently observed with a non-nucleoside reverse transcriptase inhibitor than with a protease inhibitor as the third agent. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 83 87 NNRTI;PR;NRTI 122;181;19 158;189;23 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. However, changing patterns over time in NRTIs accompanying tenofovir resulted in a persistent decreasing probability of K65R selection by tenofovir-based therapy. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 120 124 NRTI 40 45 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. METHODS: In this study, we evaluated changes over time in the selection rate of resistance mutation K65R in a large population of 2736 HIV-1-infected patients failing combination antiretroviral treatment between 2002 and 2010. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 100 104 HIV infections 135 149 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. OBJECTIVES: The use of tenofovir is highly associated with the emergence of mutation K65R, which confers broad resistance to nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs), especially when tenofovir is combined with other NRTIs also selecting for K65R. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R;K65R 85;272 89;276 RT;NRTI;NRTI 156;190;247 177;195;252 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. RESULTS: The K65R resistance mutation was detected in 144 patients, a prevalence of 5.3%. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 13 17 23027713 Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir. The currently recommended NRTI combination tenofovir/emtricitabine was associated with a low probability of K65R emergence. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 108 112 NRTI 26 30 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Collectively, our data define three major mutational pathways to high-level raltegravir and elvitegravir resistance: i) E92Q+Y143C or T97A+Y143C, ii) G140S+Q148R, and iii) E92Q+N155H. 2012 PloS one Abstract HIV E92Q;E92Q;G140S;N155H;Q148R;T97A;Y143C;Y143C 118;170;148;177;156;134;125;139 124;176;155;182;161;138;130;144 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. Analysis of the DNA sequencing data indicated that the most common mutations conferring drug resistance were M184V (38%) for NRTI and K103N (25%) for NNRTI. 2012 Diagnostic pathology Abstract HIV K103N;M184V 134;109 139;114 NNRTI;NRTI 150;125 155;129 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. Only NRTI primary mutations K101Q, K103N and the PI minor mutation L10V were found in ART naive individuals. 2012 Diagnostic pathology Abstract HIV K101Q;K103N;L10V 28;35;67 33;40;71 NRTI;PI 5;49 9;51 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. In the final paired samples that were tested while the subjects were on a raltegravir-containing regimen, DRM prevalence reached 100% in plasma but remained 1% in PBMC on day 177 post-therapy in Subject 3180 (Q148H/G140S), 100% in plasma and 36% in PBMC on day 224 in Subject 3242 (N155H), 78% in plasma and 11-12% in PBMC on day 338 in Subject 3501 (Q148H/G140S), and 100% in plasma and 0% in PBMC on day 197 in Subject 3508 (Y143R). 2012 PloS one Abstract HIV Q148H;Q148H;G140S;G140S;N155H;Y143R 351;209;357;215;282;427 356;214;362;220;287;432 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. RT subtype B virus isolates tended to acquire different ZDV resistance mutations (Q151M and D67N or T215Y, D67D/N and F214L) compared to subtype C (D67N, K70R, T215I or T215F). 2012 PloS one Abstract HIV D67D;D67N;D67N;D67N;F214L;K70R;Q151M;T215F;T215I;T215Y 107;92;107;148;118;154;82;169;160;100 113;96;113;152;123;158;88;174;165;105 RT 0 2 23061604 Resistance-associated mutations after initial antiretroviral treatment failure in a large cohort of patients infected with HIV-1 subtype CRF01_AE. The most common mutation associated with NRTI resistance was M184V/I (89.9%). 2012 Current HIV research Abstract HIV M184I;M184V 61;61 68;68 NRTI 41 45 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. CN mutations also enhanced NNRTI resistance in the presence of classical NNRTI mutations: etravirine resistance was enhanced 6- to 11-fold in the presence of L100I/K103N/Y181C. 2013 Virology Abstract HIV K103N;L100I;Y181C 164;158;170 169;163;175 NNRTI;NNRTI 27;73 32;78 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. CN mutations identified were similar to subtype B, including A376S, A400T, Q334D, G335D, N348I, and A371V, and increased AZT resistance in the presence of thymidine analog mutations. 2013 Virology Abstract HIV A371V;A376S;A400T;G335D;N348I;Q334D 100;61;68;82;89;75 105;66;73;87;94;80 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. In biochemical and antiviral assays, XZ-259 inhibits raltegravir-resistant HIV-1 integrases harboring the Y143R mutation. 2013 ACS chemical biology Abstract HIV Y143R 106 111 IN 81 91 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 2013 AIDS (London, England) Abstract HIV K65R;M184I;M184V 94;12;12 98;19;19 23080485 Low prevalence of transmitted genetic drug resistance in a cohort of HIV infected naive patients entering antiretroviral treatment programs at two sites in northern South Africa. Two drug resistance mutations (M41L and K103N) were detected in two different patients (2.5%; 95% CI: 0.0077-0.0863). 2012 Journal of medical virology Abstract HIV K103N;M41L 40;31 45;36 23080486 Unusual substitutions in HIV-1 vif from children infected perinatally without progression to AIDS for more than 8 years without therapy. However, in the deduced Vif proteins, changes V13I, V55T, and L81M were observed only in sequences from slow progressors. 2012 Journal of medical virology Abstract HIV L81M;V13I;V55T 62;46;52 66;50;56 Vif 24 27 23080489 Monitoring the emergence of resistance mutations in patients infected with HIV-1 under salvage therapy with raltegravir in Rio de Janeiro, Brazil: a follow-up study. The mutations Q148H + G140S were observed for two patients and for the third patient only mutations to PR/RT inhibitors were detected. 2012 Journal of medical virology Abstract HIV G140S;Q148H 22;14 27;19 PR;RT 103;106 105;108 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Other significant properties of Festinavir are as follows: 1) much less toxic to various cells and also to mitochondorial DNA synthesis than d4T, 2) better substrate for human thymidine kinase than d4T, 3) resistant not only to chemical glycosidic bond cleavage but also to catabolism by thymidine phosphorylase, 4) the activity improves in the presence of a major mutation, K103N, associated with resistance to non-nucleoside reverse transcriptase inhibitors. 2013 Current pharmaceutical design Abstract HIV K103N 375 380 NNRTI 412 448 23095315 Longitudinal analysis of an HLA-B*51-restricted epitope in integrase reveals immune escape in early HIV-1 infection. Reversion of the P30S polymorphism was observed by year 1 in one HLA-B*51 participant. 2013 AIDS (London, England) Abstract HIV P30S 17 21 23095315 Longitudinal analysis of an HLA-B*51-restricted epitope in integrase reveals immune escape in early HIV-1 infection. We detected that the V32I and P30X polymorphisms emerged within HLA-B*51 participants over time. 2013 AIDS (London, England) Abstract HIV P30X;V32I 30;21 34;25 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. The 68/75 patients with discordant efavirenz results harboured the V179D/E mutations compared to 7/1226 with no efavirenz discrepancy (p-value <0.001). 2012 BMC research notes Abstract HIV V179D;V179E 67;67 74;74 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. When interpreting HIVDR, especially in non-B subtypes, clinical correlation is crucial, in particular when efavirenz resistance is interpreted based on V179D/E. 2012 BMC research notes Abstract HIV V179D;V179E 152;152 159;159 23097440 Mutations in multiple domains of Gag drive the emergence of in vitro resistance to the phosphonate-containing HIV-1 protease inhibitor GS-8374. Analysis of recombinant HIV variants indicated that mutations in Gag, but not the R41K in PR, conferred reduced susceptibility to GS-8374. 2013 Journal of virology Abstract HIV R41K 82 86 Gag;PR 65;90 68;92 23097440 Mutations in multiple domains of Gag drive the emergence of in vitro resistance to the phosphonate-containing HIV-1 protease inhibitor GS-8374. The isolate showed low-level cross-resistance to darunavir, atazanavir, lopinavir, and saquinavir, but not other PIs, and contained a single R41K mutation in PR combined with multiple genotypic changes in the Gag matrix, capsid, nucleocapsid, and SP2 domains. 2013 Journal of virology Abstract HIV R41K 141 145 Capsid;Matrix;SP2;Gag;PI;PR 221;213;247;209;113;158 227;219;250;212;116;160 23097450 Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration. Here, we show that CA mutations, which include the substitution of Asp for Asn74 (N74D), significantly reduce the dependency of HIV-1 on LEDGF/p75 during infection and that this difference correlates with the efficiency of viral DNA integration. 2013 Journal of virology Abstract HIV N74D;N74D 82;67 86;80 Asp;Capsid 67;19 70;21 23097450 Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration. The distribution of integration sites mapped by Illumina sequencing confirms that the N74D mutation reduces integration into gene-rich regions of chromosomes and gene bodies and reveals previously unrecognized roles for NUP153 (another HIV-1 cofactor implicated in viral nuclear import) and LEDGF/p75 in the targeting of the viral preintegration complex to gene-dense regions of chromatin. 2013 Journal of virology Abstract HIV N74D 86 90 23099850 Rilpivirine: a new non-nucleoside reverse transcriptase inhibitor. Seventeen NNRTI mutations have been associated with decreased susceptibility to rilpivirine: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C, M230I/L, Y188L and the combination L100I + K103N. 2013 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;K103N;L100I;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 102;102;102;102;102;142;135;93;93;192;184;149;149;117;124;124;124;158 115;115;115;115;115;147;140;100;100;197;189;156;156;122;133;133;133;163 NNRTI 10 15 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. 2012 Retrovirology Abstract HIV G248A;T242N;V247I 101;34;91 106;39;96 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K) in Env and a reversion mutation in the Tat/Rev overlapping region. 2012 Retrovirology Abstract HIV R355K 124 129 Rev;Tat;Env 174;170;134 177;173;137 23115295 Inefficient vaginal transmission of tenofovir-resistant HIV-1. Here we evaluated the effect of the common tenofovir (TFV) resistance mutation K65R on vaginal HIV transmission. 2013 Journal of virology Abstract HIV K65R 79 83 23123544 Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. A new proviral construct MN4Rh-3 carrying CA-Q110D exhibited exquisitely enhanced growth property specifically in macaque cells. 2013 Microbes and infection Abstract HIV Q110D 45 50 Capsid 42 44 23123544 Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. Computer-assisted structural analysis predicted that another Q110D mutation in CA helix 6 would also increase viral growth potential. 2013 Microbes and infection Abstract HIV Q110D 61 66 Capsid 79 81 23123544 Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. HIV-1mt clones so far constructed already completely evaded TRIMCyp restriction, and further enhancement of TRIMCyp resistance by Q110D was not observed. 2013 Microbes and infection Abstract HIV Q110D 130 135 23123544 Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. In addition, Q110D did not contribute to evasion from TRIM5alpha restriction. 2013 Microbes and infection Abstract HIV Q110D 13 18 23123544 Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. In this study, viral adaptive mutation in macaque cells, G114E in capsid (CA) helix 6 of HIV-1mt, that enhances viral replication was identified. 2013 Microbes and infection Abstract HIV G114E 57 62 Capsid;Capsid 66;74 72;76 23123544 Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells. Our results here indicate that CA-Q110D accelerates viral growth in macaque cells irrelevant to TRIM5 proteins restriction. 2013 Microbes and infection Abstract HIV Q110D 34 39 Capsid 31 33 23136365 Gag sequence variation in a human immunodeficiency virus type 1 transmission cluster influences viral replication fitness. Interestingly, HIV-1 variants from patients with a progressive clinical course of infection developed compensatory mutations within the capsid that restored viral fitness, instead of reversion of the T242S mutation. 2013 The Journal of general virology Abstract HIV T242S 200 205 Capsid 136 142 23136365 Gag sequence variation in a human immunodeficiency virus type 1 transmission cluster influences viral replication fitness. Viral gag sequences from all three patients contained a mutation at position 242, T242N or T242S, which have been associated with lower virus replication in vitro. 2013 The Journal of general virology Abstract HIV T242N;T242S 82;91 87;96 Gag 6 9 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. In the current study we have tested the single-walled carbon nanotube (SWCNT) as an inhibitor in wild type (WT) as well as in three primary mutants (I50V(PR), V82A(PR) and I84V(PR)) of the HIV-1-PR through docking the SWCNT in the active site region, and then performed all-atom MD simulations for the complexes. 2012 Journal of molecular graphics & modelling Abstract HIV I50V;I84V;V82A 149;172;159 154;176;163 PR;PR;PR;PR 154;164;177;195 156;166;179;197 23144597 Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation. Flap+ is a multi-drug-resistant variant of HIV-1 protease with a combination of mutations at the edge of the active site, within the active site, and in the flaps (L10I, G48V, I54V, V82A). 2012 Journal of chemical theory and computation Abstract HIV G48V;I54V;L10I;V82A 170;176;164;182 174;180;168;186 PR 49 57 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Although the impact of the other six mutations on response to NVP was minimal, mutation T369V could enhance resistance to NVP. 2012 PloS one Abstract HIV T369V 88 93 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Phenotypic characterization of these HIV mutants revealed that constructed viruses with mutations A371V and T369V exhibited dual resistance to AZT and EFV respectively, whereas the other 5 mutations showed weak resistance. 2012 PloS one Abstract HIV A371V;T369V 98;108 103;113 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. RESULTS: 7 mutations at 6 positions of the RT region, D123E, V292I, K366R, T369A, T369V, A371V and I375V, occurred more frequently in the ART failure group than the naive-therapy group. 2012 PloS one Abstract HIV A371V;D123E;I375V;K366R;T369A;T369V;V292I 89;54;99;68;75;82;61 94;59;104;73;80;87;66 RT 43 45 23149229 6,7-Dihydroxy-1-oxoisoindoline-4-sulfonamide-containing HIV-1 integrase inhibitors. We have developed several sulfonamide-containing analogs that enhance potency in cell-based HIV assays by more than two orders-of-magnitude and we describe several compounds that are more potent than raltegravir against the clinically relevant Y143R IN mutant. 2012 Bioorganic & medicinal chemistry letters Abstract HIV Y143R 244 249 IN 250 252 23152614 Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. Point mutations in either the core region (K41A) or the cysteine-rich region (C30G) of Tat abrogated its ability to inhibit beta-catenin signaling. 2012 The Journal of neuroscience Abstract HIV C30G;K41A 78;43 82;47 Tat 87 90 23161095 HIV-1 drug resistance-associated mutations among antiretroviral-naive Thai patients with chronic HIV-1 infection. DRAMs to NNRTIs were V106I (7%), V179D (4.2%), V179T (1.8%), E138A (1.5%), V90I (1.2%), K103N (0.9%), Y181C (0.9%), and P225H (0.3%). 2013 Journal of medical virology Abstract HIV E138A;K103N;P225H;V106I;V179D;V179T;V90I;Y181C 61;88;120;21;33;47;75;102 66;93;125;26;38;52;79;107 NNRTI 9 15 23161095 HIV-1 drug resistance-associated mutations among antiretroviral-naive Thai patients with chronic HIV-1 infection. DRAMs to NRTIs were M184V (0.3%) and T215S (0.3%). 2013 Journal of medical virology Abstract HIV M184V;T215S 20;37 25;42 NRTI 9 14 23161095 HIV-1 drug resistance-associated mutations among antiretroviral-naive Thai patients with chronic HIV-1 infection. Minor DRAMs to PIs including I13V, M36I, H69K, and L89M were observed more frequently in CRF_01 AE. 2013 Journal of medical virology Abstract HIV H69K;I13V;L89M;M36I 41;29;51;35 45;33;55;39 PI 15 18 23161095 HIV-1 drug resistance-associated mutations among antiretroviral-naive Thai patients with chronic HIV-1 infection. The only major DRAM for PIs was M46L (0.6%). 2013 Journal of medical virology Abstract HIV M46L 32 36 PI 24 27 23164656 Synthesis, structure-activity relationships, and docking studies of N-phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse transcriptase inhibitors. Moreover, all of them were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with EC(50) values of 0.29 muM, 0.14 muM, 0.10 muM and 0.27 muM, respectively. 2012 European journal of medicinal chemistry Abstract HIV K103N;Y181C 82;90 88;95 23173702 Short communication: HIV type 1 transmitted drug resistance and evidence of transmission clusters among recently infected antiretroviral-naive individuals from Ugandan fishing communities of Lake Victoria. Nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was identified in two individuals and V106A in one (6%) suggesting that the level of TDR was moderate in this population. 2013 AIDS research and human retroviruses Abstract HIV K103N;V106A 79;123 84;128 NNRTI;NNRTI 0;47 35;52 23173702 Short communication: HIV type 1 transmitted drug resistance and evidence of transmission clusters among recently infected antiretroviral-naive individuals from Ugandan fishing communities of Lake Victoria. Of these, one pair included the two individuals with K103N. 2013 AIDS research and human retroviruses Abstract HIV K103N 53 58 23178942 Regulation of telomere length and homeostasis by telomerase enzyme processivity. Human TERT-L866Y, like wild-type human TERT, can immortalize and extend the lifespan of limited-lifespan cells. 2013 Journal of cell science Abstract HIV L866Y 11 16 23178942 Regulation of telomere length and homeostasis by telomerase enzyme processivity. Moreover, cells expressing human TERT-L866Y display heterogenous telomere lengths, telomere elongation, multiple telomeric signals indicative of fragile sites and replicative stress, and an increase in short telomeres, which is accompanied by telomere trimming events. 2013 Journal of cell science Abstract HIV L866Y 38 43 23178942 Regulation of telomere length and homeostasis by telomerase enzyme processivity. To investigate the role of increased telomerase processivity on telomere length regulation in human cells with limited lifespan that are dependent on human TERT for lifespan extension and immortalization, we mutated the leucine at position 866 in the reverse transcriptase C motif of human TERT to a tyrosine (L866Y), which is the amino acid found at the equivalent position in HIV-1 reverse transcriptase. 2013 Journal of cell science Abstract HIV L866Y 310 315 RT;RT 251;384 272;405 23178942 Regulation of telomere length and homeostasis by telomerase enzyme processivity. We report that, similar to the previously reported gain-of-function Tetrahymena telomerase mutant (L813Y), the human telomerase variant displays increased processivity. 2013 Journal of cell science Abstract HIV L813Y 99 104 23180144 HIV Drug Resistance and the Advent of Integrase Inhibitors. Here, we provide new information about the most recent mutations identified and other mutations that confer resistance to several integrase inhibitors, such as new resistance mutations-for example, G118R, R263K, and S153Y-that have been identified through in vitro selection studies with second-generation integrase strand transfer inhibitors (INSTIs). 2013 Current infectious disease reports Abstract HIV G118R;R263K;S153Y 198;205;216 203;210;221 IN;IN;INSTI 130;306;344 139;315;350 23183438 HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir. K65R selection was significantly higher in HIV-1 subtype C. 2013 Antimicrobial agents and chemotherapy Abstract HIV K65R 0 4 23183438 HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir. Subtype-dependent selection of HIV-1 reverse transcriptase resistance mutation K65R was previously observed in cell culture and small clinical investigations. 2013 Antimicrobial agents and chemotherapy Abstract HIV K65R 79 83 RT 37 58 23183438 HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir. This could not be explained by clinical and demographic factors in multivariate analysis, suggesting subtype sequence-specific K65R pathways. 2013 Antimicrobial agents and chemotherapy Abstract HIV K65R 127 131 23183438 HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir. We compared K65R prevalence across subtypes A, B, C, F, G, and CRF02_AG separately in a cohort of 3,076 patients on combination therapy including tenofovir. 2013 Antimicrobial agents and chemotherapy Abstract HIV K65R 12 16 23187937 HIV-2 antiviral potency and selection of drug resistance mutations by the integrase strand transfer inhibitor elvitegravir and NRTIs emtricitabine and tenofovir in vitro. HIV-2 site-directed mutant (SDM) viruses with E92G and E92Q integrase mutations showed 3.7- and 16-fold reduced susceptibilities to EVG, respectively. 2013 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E92G;E92Q 46;55 50;59 IN 60 69 23187937 HIV-2 antiviral potency and selection of drug resistance mutations by the integrase strand transfer inhibitor elvitegravir and NRTIs emtricitabine and tenofovir in vitro. In resistance selections, EVG selected E92G/Q and S147N in integrase, FTC selected M184V/I in RT, and TFV selected K65R and Y115F in RT. 2013 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E92G;E92Q;K65R;M184I;M184V;S147N;Y115F 39;39;115;83;83;50;124 45;45;119;90;90;55;129 IN;RT;RT 59;94;133 68;96;135 23187937 HIV-2 antiviral potency and selection of drug resistance mutations by the integrase strand transfer inhibitor elvitegravir and NRTIs emtricitabine and tenofovir in vitro. The RT K65R SDM virus had 2.2- and 9.1-fold reduced susceptibilities to TFV and FTC, respectively, and the addition of Y115F to K65R further decreased susceptibility to both drugs. 2013 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;K65R;Y115F 7;128;119 11;132;124 RT 4 6 23187937 HIV-2 antiviral potency and selection of drug resistance mutations by the integrase strand transfer inhibitor elvitegravir and NRTIs emtricitabine and tenofovir in vitro. The RT M184I and M184V SDM viruses were both highly resistant to FTC (34- and >1000-fold, respectively). 2013 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 7;17 12;22 RT 4 6 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. The most frequent DRMs were K103N/S (46.1%) and M184V/I (37.6%). 2012 Journal of the International AIDS Society Abstract HIV K103N;K103S;M184I;M184V 28;28;48;48 35;35;55;55 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Here we show that HSP90AB1 is present in HIV virions and that HSP90AB1, but not nonfunctional mutated HSP90AB1(E42A+D88A), restores infectivity to HIV with mutations in CA that alter core stability. 2013 Virology Abstract HIV E42A;D88A 111;116 115;120 Capsid 169 171 23208549 Escherichia coli LysU is a potential surrogate for human lysyl tRNA synthetase in interactions with the C-terminal domain of HIV-1 capsid protein. After confirming that LysU and CA(146) are dimeric whilst CA(151) and M185A remain monomeric, we use glutathione S-transferase (GST) pull-down assays to demonstrate the existence of specific interactions between LysU and all three CA-C domains. 2013 Organic & biomolecular chemistry Abstract HIV M185A 70 75 Capsid;Capsid;Capsid 31;58;231 33;60;233 23208549 Escherichia coli LysU is a potential surrogate for human lysyl tRNA synthetase in interactions with the C-terminal domain of HIV-1 capsid protein. By means of (1)H-NMR titration experiments, we estimate K(d) values of 50 muM for the interaction between LysU and CA(146) or >500 muM for interactions between LysU and CA(151) or LysU and M185A. 2013 Organic & biomolecular chemistry Abstract HIV M185A 189 194 Capsid;Capsid 115;169 117;171 23208549 Escherichia coli LysU is a potential surrogate for human lysyl tRNA synthetase in interactions with the C-terminal domain of HIV-1 capsid protein. We report on a series of studies involving three CA C-domains: CA(146) (intact domain), CA(151) (truncated domain), and CA(146)-M185A (M185A, CA dimer interface mutant). 2013 Organic & biomolecular chemistry Abstract HIV M185A;M185A 135;128 140;133 Capsid;Capsid;Capsid;Capsid;Capsid 49;63;88;120;142 51;65;90;122;144 23211777 Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term nonprogressors. CONCLUSION: Although identified in a cohort of long-term nonprogressors, our study did not indicate that the I436S or T473I mutation in LEDGF/p75 affects the interaction with HIV-1 integrase. 2013 AIDS (London, England) Abstract HIV I436S;T473I 109;118 114;123 IN 181 190 23211777 Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term nonprogressors. Here, we study two LEDGF/p75 exonic variants I436S and T473I, identified in HIV-1 long-term nonprogressors, together with Q472L. 2013 AIDS (London, England) Abstract HIV I436S;Q472L;T473I 45;122;55 50;127;60 23211777 Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term nonprogressors. RESULTS: Binding affinities of wild-type, I436S, T473I, and Q472L LEDGF/p75 for HIV-1 integrase were comparable. 2013 AIDS (London, England) Abstract HIV I436S;Q472L;T473I 42;60;49 47;65;54 IN 86 95 23230246 Baseline-transmitted V106V/I/M non-nucleoside reverse transcriptase inhibitor resistance in HIV-1 subtype B infection. The V106V/I/M mutation represents a mixture of virus strains conferring resistance to the non-nucleoside reverse transcriptase inhibitor antiretrovirals efavirenz and nevirapine. 2012 BMJ case reports Abstract HIV V106I;V106M;V106V 4;4;4 13;13;13 NNRTI 90 126 23230246 Baseline-transmitted V106V/I/M non-nucleoside reverse transcriptase inhibitor resistance in HIV-1 subtype B infection. V106M mutation is not often observed as a primary resistance mutation in patients infected with HIV-1 subtype B. 2012 BMJ case reports Abstract HIV V106M 0 5 23230246 Baseline-transmitted V106V/I/M non-nucleoside reverse transcriptase inhibitor resistance in HIV-1 subtype B infection. We report a case in which an antiretroviral therapy (ART)-naive patient diagnosed with HIV-1 subtype B presented with baseline genotype and phenotype resistance tests, confirming a V106V/I/M nucleoside resistance mutation. 2012 BMJ case reports Abstract HIV V106I;V106M;V106V 181;181;181 190;190;190 23231029 Exploring the molecular mechanism of cross-resistance to HIV-1 integrase strand transfer inhibitors by molecular dynamics simulation and residue interaction network analysis. On the basis of the homology modeling constructed structure of tetrameric HIV-1 intasome, the detailed molecular mechanism of the cross-resistance mutation E138K/Q148K to three important INSTIs (Raltegravir (RAL, FDA approved in 2007), Elvitegravir (EVG, FDA approved in 2012), and Dolutegravir (DTG, phase III clinical trials)) was investigated by using molecular dynamics (MD) simulation and residue interaction network (RIN) analysis. 2013 Journal of chemical information and modeling Abstract HIV E138K;Q148K 156;162 161;167 INSTI 187 193 23236061 Distinct HIV-1 escape patterns selected by cytotoxic T cells with identical epitope specificity. An in vitro viral suppression assay revealed that the HLA-B*52:01-restricted CTLs failed to suppress the replication of the I135X mutant viruses, indicating the selection of these mutants by the CTLs. 2013 Journal of virology Abstract HIV I135X 124 129 23236061 Distinct HIV-1 escape patterns selected by cytotoxic T cells with identical epitope specificity. However, these CTLs select for the reverse transcriptase (RT) I135X escape mutation, which may be accumulating in circulating HIV-1 sequences. 2013 Journal of virology Abstract HIV I135X 60 67 RT;RT 35;58 56;60 23236061 Distinct HIV-1 escape patterns selected by cytotoxic T cells with identical epitope specificity. Population level analyses revealed a strong association of HLA-B*51:01 with the I135T mutant and a relatively weaker association of HLA-B*52:01 with several I135X mutants in both Japanese and predominantly Caucasian cohorts. 2013 Journal of virology Abstract HIV I135T;I135X 80;157 85;162 23236061 Distinct HIV-1 escape patterns selected by cytotoxic T cells with identical epitope specificity. These results suggest that the different pattern of I135X mutant selection may have resulted from the difference between these two CTLs in the ability to suppress HIV-1 replication. 2013 Journal of virology Abstract HIV I135X 52 57 23236061 Distinct HIV-1 escape patterns selected by cytotoxic T cells with identical epitope specificity. We investigated the selection of the I135X mutation by CTLs specific for the same epitope but restricted by HLA-B*52:01. 2013 Journal of virology Abstract HIV I135X 37 42 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? All of them (100%) showed M184V resistance associated mutation to lamivudine as well as NNRTI's RAMS. 2012 PloS one Abstract HIV M184V 26 31 NNRTI 88 93 23241378 HIV-1 genetic diversity and drug resistance among Senegalese patients in the public health system. For non-NRTI resistance, we noted a predominance of the K103N mutation (46.27%). 2013 Journal of clinical microbiology Abstract HIV K103N 56 61 NNRTI 4 12 23241378 HIV-1 genetic diversity and drug resistance among Senegalese patients in the public health system. For PI/r, several cases of mutations were found with a predominance of M46I and L76V/F at 24% each. 2013 Journal of clinical microbiology Abstract HIV L76F;L76V;M46I 80;80;71 86;86;75 PI 4 6 23241378 HIV-1 genetic diversity and drug resistance among Senegalese patients in the public health system. In NRTI mutations, thymidine analog mutations (TAMs) were found in 50.79% and the M184V mutation was found in 34.92% of the samples. 2013 Journal of clinical microbiology Abstract HIV M184V 82 87 NRTI 3 7 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. A particular drug resistant variant (L10I/G48V/I54V/V82A) displays extreme entropy-enthalpy compensation relative to wild-type enzyme but a similar variant (L10I/G48V/I54A/V82A) does not. 2013 ACS chemical biology Abstract HIV L10I;L10I;G48V;G48V;I54A;I54V;V82A;V82A 157;37;162;42;167;47;52;172 161;41;166;46;171;51;56;176 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. In particular, an E407K mutation at the base of the V3 loop knocks out CD134 binding; enhances HSPG binding; and in combination with additional Env mutations E656K and V817I increases entry into CD134(-), CXCR4(+) target cells by greater than 80-fold over wild type FIV-PPR. 2012 Retrovirology Abstract HIV E407K;E656K;V817I 18;158;168 23;163;173 Env 144 147 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Among 12 (26.1%) raltegravir treated patients treatment failure was observed; major InI drug resistance mutations (G140S, Q148H and N155H, V151I, E92EQ, V151I, G163R) were noted in four of these cases (8.3% of the total InI-treated patients). 2012 BMC infectious diseases Abstract HIV E92E;E92Q;G140S;G163R;N155H;Q148H;V151I;V151I 146;146;115;160;132;122;139;153 151;151;120;165;137;127;144;158 IN;IN 84;220 87;223 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Baseline polymorphisms, including E157Q were not associated with the virologic failure on raltegravir. 2012 BMC infectious diseases Abstract HIV E157Q 34 39 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. In 30 (38.5%) cases polymorphic variation with predominance of the E157Q mutation was observed. 2012 BMC infectious diseases Abstract HIV E157Q 67 72 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Other variants included L68V, L74IL, T97A, E138D, V151I, R263K. 2012 BMC infectious diseases Abstract HIV E138D;L68V;L74I;L74L;R263K;T97A;V151I 43;24;30;30;57;37;50 48;28;35;35;62;41;55 23262501 Distinct resistance patterns to etravirine and rilpivirine in viruses containing nonnucleoside reverse transcriptase inhibitor mutations at baseline. CONCLUSION: These results demonstrate that ETR and RPV are likely to select for E138K as a major resistance mutation if no or very few other resistance mutations are present and that Y181C may be antagonistic to E138K. 2013 AIDS (London, England) Abstract HIV E138K;E138K;Y181C 80;212;183 85;217;188 23262501 Distinct resistance patterns to etravirine and rilpivirine in viruses containing nonnucleoside reverse transcriptase inhibitor mutations at baseline. However, subtype B viruses containing Y181C generated V179I/F or A62V/A but not E138K following exposure to ETR or RPV, respectively, whereas subtype C viruses containing Y181C developed E138V together with Y188H and V179I under ETR pressure. 2013 AIDS (London, England) Abstract HIV A62A;A62V;E138K;E138V;V179F;V179I;V179I;Y181C;Y181C;Y188H 65;65;80;187;54;54;217;38;171;207 71;71;85;192;61;61;222;43;176;212 23262501 Distinct resistance patterns to etravirine and rilpivirine in viruses containing nonnucleoside reverse transcriptase inhibitor mutations at baseline. RESULTS: In wild-type viruses and viruses containing K103N alone at baseline, E138K or E138G mutations were observed following pressure with either ETR or RPV prior to the appearance of other NNRTI resistance mutations. 2013 AIDS (London, England) Abstract HIV E138G;E138K;K103N 87;78;53 92;83;58 NNRTI 192 197 23262501 Distinct resistance patterns to etravirine and rilpivirine in viruses containing nonnucleoside reverse transcriptase inhibitor mutations at baseline. The addition of mutations at position 138 to Y181C did not significantly enhance levels of resistance to ETR or RPV. 2013 AIDS (London, England) Abstract HIV Y181C 45 50 23262501 Distinct resistance patterns to etravirine and rilpivirine in viruses containing nonnucleoside reverse transcriptase inhibitor mutations at baseline. The replicative capacity of viruses containing Y181C and either E138K or E138A was similar to that of viruses containing either E138K or E138A alone. 2013 AIDS (London, England) Abstract HIV E138A;E138A;E138K;E138K;Y181C 73;137;64;128;47 78;142;69;133;52 23264671 Impact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure. Among participants on efavirenz, K103N was the most frequently observed resistance mutation at virologic failure regardless of the baseline minority variant. 2013 The Journal of infectious diseases Abstract HIV K103N 33 38 23264671 Impact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure. However, the presence of baseline Y181C minority variant was associated with a higher probability of Y181C detection after virologic failure. 2013 The Journal of infectious diseases Abstract HIV Y181C;Y181C 34;101 39;106 23269800 Enhancement of antiviral activity of human alpha-defensin 5 against herpes simplex virus 2 by arginine mutagenesis at adaptive evolution sites. Furthermore, the E21R variant exhibited a 2-fold-higher antiviral potency against HIV-1 over parental HD5 in vitro. 2013 Journal of virology Abstract HIV E21R 17 21 23269800 Enhancement of antiviral activity of human alpha-defensin 5 against herpes simplex virus 2 by arginine mutagenesis at adaptive evolution sites. In a mouse model of lethal HSV-2 infection, prophylactic and/or therapeutic treatment with E21R-HD5 via intravaginal instillation remarkably alleviated the symptoms and delayed disease progress and resulted in about a 1.5-fold-higher survival rate than in the HD5 group. 2013 Journal of virology Abstract HIV E21R 91 95 23269800 Enhancement of antiviral activity of human alpha-defensin 5 against herpes simplex virus 2 by arginine mutagenesis at adaptive evolution sites. Inspiringly, the E21R-HD5 mutant had significantly higher antiviral activity than natural HD5, which is possibly attributed to the stronger binding affinity of the E21R-HD5 mutant with HSV-2 capsid protein gD, indicating that E21R mutation can increase the anti-HSV-2 potency of HD5. 2013 Journal of virology Abstract HIV E21R;E21R;E21R 17;164;226 21;168;230 Capsid 191 197 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. A total of 1.3% of DR were related to protease inhibitors (PIs), including I85IV, M46I and L90M; 0.3% to nucleoside reverse transcriptase inhibitors (NRTIs), including M184I; and 2.7% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including K103N/S, Y181C, K101E and G190A. 2012 BMC infectious diseases Abstract HIV G190A;I85I;I85V;K101E;K103N;K103S;L90M;M184I;M46I;Y181C 281;75;75;271;255;255;91;168;82;264 286;80;80;276;262;262;95;173;86;269 NNRTI;NRTI;PR;NNRTI;NRTI;PI 187;105;38;236;150;59 223;137;46;242;155;62 23271577 Specific VpU codon changes were significantly associated with gp120 V3 tropic signatures in HIV-1 B-subtype. Beyond the classical V3 signatures (R5-viruses: S11, E25D; X4-viruses: S11KR, E25KRQ), other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. 2012 Virologica Sinica Abstract HIV E25D;E25K;E25Q;E25R;S11K;S11R 53;78;78;78;71;71 57;84;84;84;76;76 Vpu 115 118 23271577 Specific VpU codon changes were significantly associated with gp120 V3 tropic signatures in HIV-1 B-subtype. The dendrogram showed two distinct large clusters: one associated with R5-tropic sequences (bootstrap=0.94), involving: (a) H13NP(V3), E25D(V3), S11(V3), T22A(V3) and Q61H(VpU), (b) E25A(V3) and L12F(VpU), (c) D44E(VpU), R18Q(V3) and D80N(VpU); and another associated with X4-tropic sequences (bootstrap=0.97), involving: (i) E25I(V3) and V10A(VpU), (ii) 0-1insV(VpU), H13R(V3), I46L(VpU), I30M(V3) and 60-62del(VpU), (iii) S11KR(V3) and E25KRQ(V3). 2012 Virologica Sinica Abstract HIV D44E;D80N;E25A;E25D;E25I;E25K;E25Q;E25R;H13N;H13P;H13R;I30M;I46L;L12F;Q61H;R18Q;S11K;S11R;T22A;V10A 208;234;180;135;324;438;438;438;122;122;369;390;379;195;167;221;422;422;154;339 214;238;186;139;330;444;444;444;129;129;373;394;383;199;171;225;429;429;158;343 Vpu;Vpu;Vpu;Vpu;Vpu;Vpu;Vpu;Vpu 172;200;215;239;344;363;384;412 175;203;218;242;347;366;387;415 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. In addition, the N348I substitution decreases the RNase H cleavage of DNA terminated with EFdA-MP (T/P(EFdA-MP)). 2012 Cellular and molecular biology (Noisy-le-Grand, France) Abstract HIV N348I 17 22 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. In this study we tested EFdA-triphosphate (TP) together with a related compound, ENdA-TP (4'-ethynyl-2-amino-2'-deoxdyadenosine triphosphate) against HIV-1 RTs that carry clinically relevant drug resistance mutations: N348I, D67N/K70R/L210Q/T215F, D67N/K70R/L210Q/T215F/N348I, and A62V/V5I/F77L/F116Y/Q151M. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Abstract HIV A62V;D67N;D67N;F116Y;F77L;K70R;K70R;L210Q;L210Q;N348I;Q151M;T215F;T215F;V5I;N348I 281;225;248;295;290;253;230;235;258;270;301;241;264;286;218 285;229;252;300;294;257;234;240;263;275;306;246;269;289;223 RT 156 159 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Moreover, N348I RT unblocks EFdA-terminated primers with similar efficiency as the WT enzyme, and further enhances EFdA unblocking in the background of AZT-resistance mutations. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Abstract HIV N348I 10 15 RT 16 18 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Similar to WT RT, the N348I RT is inhibited by EFdA mainly at the point of incorporation through decreased translocation. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Abstract HIV N348I 22 27 RT;RT 14;28 16;30 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The N348I mutation at the connection subdomain (CS) of HIV-1 RT confers clinically significant resistance to both nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). 2012 Cellular and molecular biology (Noisy-le-Grand, France) Abstract HIV N348I 4 9 NNRTI;NRTI;RT;RT 167;126;61;152 173;131;63;154 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. This study provides biochemical insights into the mechanism of inhibition of N348I RT by TDRTIs and highlights the excellent efficacy of this class of inhibitors against WT and drug-resistant HIV-1 RTs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Abstract HIV N348I 77 82 RT;RT 83;198 85;201 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. Detection of M184V (3TC resistance) by RNA-OLA and DNA-OLA demonstrated a sensitivity of 0.93 and 0.86 and specificity of 0.67 and 0.7, respectively, for the identification of virologic failure. 2013 BMC infectious diseases Abstract HIV M184V 13 18 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The RT mutations N88D and L90M (NFV resistance) detected by DNA-OLA correlated with virologic failure, whereas mutations at RT position 215 (AZT resistance) were not associated with virologic failure. 2013 BMC infectious diseases Abstract HIV L90M;N88D 26;17 30;21 RT;RT 4;124 6;126 23280502 Some hydrazones of 2-aroylamino-3-methylbutanohydrazide: synthesis, molecular modeling studies, and identification as stereoselective inhibitors of HIV-1. Hydrazones 8(S) , 11(S) , and 12(S) which were active against HIV-1 wild type showed no inhibition against a double mutant NNRTI-resistant strain (K103N;Y181C). 2013 Archiv der Pharmazie Abstract HIV K103N;Y181C 147;153 152;158 NNRTI 123 128 23284027 Evaluation of a benchtop HIV ultradeep pyrosequencing drug resistance assay in the clinical laboratory. Additional patient harbored low-abundance V32I major protease inhibitor mutation, which under darunavir selection evolved later to be detected by TruGene. 2013 Journal of clinical microbiology Abstract HIV V32I 42 46 PR 53 61 23284027 Evaluation of a benchtop HIV ultradeep pyrosequencing drug resistance assay in the clinical laboratory. Several patients had low-abundance D67N, K70R, and M184V reverse transcriptase inhibitor mutations that persisted long after discontinuation of the drug that elicited these mutations. 2013 Journal of clinical microbiology Abstract HIV D67N;K70R;M184V 35;41;51 39;45;56 RT 57 78 23289841 Factors associated with virological success with raltegravir-containing regimens and prevalence of raltegravir-resistance-associated mutations at failure in the ARCA database. Mutations associated with RAL failure were detected in 12/24 subjects with an integrase genotype, with the prevalence of Q148H + G140S. 2013 Clinical microbiology and infection Abstract HIV G140S;Q148H 129;121 134;126 IN 78 87 23296905 Molecular epidemiology of HIV in a cohort of men having sex with men from Istanbul. In these patients, the nucleoside reverse transcriptase inhibitor (NRTI)-associated resistance mutations M41L, T215C, V75I, T69N, the non-NRTI associated mutations V106I, E138A, K103N and the protease inhibitor associated mutations Q58E and V82I were detected. 2013 Medical microbiology and immunology Abstract HIV E138A;K103N;M41L;Q58E;T215C;T69N;V106I;V75I;V82I 171;178;105;232;111;124;164;118;241 176;183;109;236;116;128;169;122;245 NRTI;NNRTI;PR;NRTI 23;134;192;67 55;142;200;71 23297633 [Prevalence of mutations responsible for resistance to antiretroviral preparations among HIV-1 variants circulating in Novosibirsk region]. The most prevalent mutations are those conditioning resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors (M184V, Y181C and K103N). 2012 Zhurnal mikrobiologii, epidemiologii i immunobiologii Abstract HIV K103N;M184V;Y181C 147;130;137 152;135;142 NNRTI 81 117 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Asn30 in PR(D30N) showed altered interactions with neighboring residues and 18-fold worse inhibition. 2013 Journal of medicinal chemistry Abstract HIV D30N 12 16 PR 9 11 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Gln8 in PR(R8Q) replaced the ionic interactions of wild type Arg8 with hydrogen bond interactions without changing the inhibition significantly. 2013 Journal of medicinal chemistry Abstract HIV R8Q 11 14 PR 8 10 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutations V82A and I54M showed compensating structural changes consistent with 6-7-fold lower inhibition. 2013 Journal of medicinal chemistry Abstract HIV I54M;V82A 19;10 23;14 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. The high resolution X-ray crystal structures of inhibitor 1 in complexes with single substitution mutants PR(R8Q), PR(D30N), PR(I50V), PR(I54M), and PR(V82A) were analyzed in relation to kinetic data. 2013 Journal of medicinal chemistry Abstract HIV D30N;I50V;I54M;R8Q;V82A 118;128;138;109;152 122;132;142;112;156 PR;PR;PR;PR;PR 106;115;125;135;149 108;117;127;137;151 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. The smaller valine side chain in PR(I50V) eliminated hydrophobic interactions with inhibitor and the other subunit consistent with 60-fold worse inhibition. 2013 Journal of medicinal chemistry Abstract HIV I50V 36 40 PR 33 35 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations. 2013 Bioorganic & medicinal chemistry letters Abstract HIV Y181C 98 107 RT 45 66 23300238 Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV. 3TC/FTC-resistant mutants (M184V/I) emerged infrequently (7/134 [5%]), and their occurrence did not differ by arm. 2013 Clinical infectious diseases Abstract HIV M184I;M184V 27;27 34;34 23300238 Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV. Four hundred twelve (98%) women had primary endpoint results available; of these, 5 (1.2%) had new NVP resistance detected by population genotype: 4 of 215 in the 7-day arms (1.9%; K103N in 4 women with Y181C, Y188C, or G190A in 3 of 4) and 1 of 197 (0.5%; V108I) in the 21-day arms (P = .37). 2013 Clinical infectious diseases Abstract HIV G190A;K103N;V108I;Y181C;Y188C 220;181;257;203;210 225;186;262;208;215 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. CONCLUSIONS: Prevalence of transmitted K65R and other tenofovir resistance mutations across diverse HIV-1 subtypes and recombinants is low, suggesting minimal effect on tenofovir-containing PrEP regimens. 2012 Journal of the International AIDS Society Abstract HIV K65R 39 43 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Differences in the prevalence of K65R between HIV-1 subtypes were not statistically significant. 2012 Journal of the International AIDS Society Abstract HIV K65R 33 37 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. K65R was found in 20 sequences (0.1%, 95% CI: 0.06 to 0.15). 2012 Journal of the International AIDS Society Abstract HIV K65R 0 4 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. K70E and >=3 TAMs were found in 0.015% (95% CI: 0.004 to 0.04) and 0.27% (95% CI: 0.2 to 0.4) of sequences, respectively. 2012 Journal of the International AIDS Society Abstract HIV K70E 0 4 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Tenofovir-associated resistance mutations included K65R, K70E, T69-insertion and >=3 thymidine analogue mutations (TAMs), inclusive of M41L or L210W. 2012 Journal of the International AIDS Society Abstract HIV K65R;K70E;L210W;M41L 51;57;143;135 55;61;148;139 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Transmitted drug resistance mutations associated with tenofovir, specifically the reverse transcriptase (RT) mutation K65R, may impact the effectiveness of PrEP. 2012 Journal of the International AIDS Society Abstract HIV K65R 118 122 RT;RT 82;105 103;107 23308067 Human tetherin exerts strong selection pressure on the HIV-1 group N Vpu protein. We found that these N-Vpus acquired four amino acid substitutions (E15A, V19A and IV25/26LL) in their transmembrane domain (TMD) that allow efficient interaction with human tetherin. 2012 PLoS pathogens Abstract HIV E15A;V19A 67;73 71;77 Vpu 22 26 23308370 Antiretroviral drug resistance profiles and response to second-line therapy among HIV type 1-infected Ugandan children. Multiple RAMs were observed among HIV-1-infected children with virological failure on first-line ART with M184V and K103N most frequent. 2013 AIDS research and human retroviruses Abstract HIV K103N;M184V 116;106 121;111 HIV infections 34 48 23308370 Antiretroviral drug resistance profiles and response to second-line therapy among HIV type 1-infected Ugandan children. TAMs,>=3 TAMs, 69 insertion complex, K65R/N, and Q151M were observed in 43.0%, 10.6%, 18.3%, 2.8%, and 2.1% of the children, respectively. 2013 AIDS research and human retroviruses Abstract HIV K65N;K65R;Q151M 37;37;49 43;43;54 23308370 Antiretroviral drug resistance profiles and response to second-line therapy among HIV type 1-infected Ugandan children. The commonest nonnucleoside reverse transcriptase inhibitor (NNRTI) RAM was K103N in 72/142 (50.7%) children. 2013 AIDS research and human retroviruses Abstract HIV K103N 76 81 NNRTI;NNRTI 14;61 49;66 23308370 Antiretroviral drug resistance profiles and response to second-line therapy among HIV type 1-infected Ugandan children. The commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was M184V in 129/142 (90.8%) children. 2013 AIDS research and human retroviruses Abstract HIV M184V 72 77 NRTI;NRTI 14;58 46;62 23308370 Antiretroviral drug resistance profiles and response to second-line therapy among HIV type 1-infected Ugandan children. The pattern of RAMs was determined in frequency runs and the factors associated with accumulation of>=3 thymidine analogue mutations (TAMs) and K103N were determined using multivariate logistic models. 2013 AIDS research and human retroviruses Abstract HIV K103N 144 149 23308370 Antiretroviral drug resistance profiles and response to second-line therapy among HIV type 1-infected Ugandan children. The starting ART regimen was associated with accumulation of both>=3 TAMs (p=0.046) and K103N (p<0.0001), while a history of poor adherence was associated with K103N accumulation (p=0.0388). 2013 AIDS research and human retroviruses Abstract HIV K103N;K103N 88;160 93;165 23325683 Cyclophilin A-dependent restriction to capsid N121K mutant human immunodeficiency virus type 1 in a broad range of cell lines. Here, we identified a CA N121K mutant whose infection of 293T, Jurkat, and HeLa cells was impaired by CypA. 2013 Journal of virology Abstract HIV N121K 25 30 Capsid 22 24 23325683 Cyclophilin A-dependent restriction to capsid N121K mutant human immunodeficiency virus type 1 in a broad range of cell lines. The N121K mutant could be a useful tool for analyzing the mechanisms underlying CypA-dependent restriction. 2013 Journal of virology Abstract HIV N121K 4 9 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. CONCLUSIONS: We showed an impact of viral subtype on the selection of the L76V major PI-RAM with a higher prevalence in "non-B" subtypes observed since 2008. 2013 PloS one Abstract HIV L76V 74 78 PI 85 87 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. METHODS: Frequency of the L76V mutation between 1998 and 2010 was surveyed in the laboratory database of 3 clinical centers. 2013 PloS one Abstract HIV L76V 26 30 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. OBJECTIVE: To describe the prevalence of the L76V protease inhibitors resistance-associated mutation (PI-RAM) in relation with patients' characteristics and protease genotypic background in HIV-1 B- and "non-B"-infected patients. 2013 PloS one Abstract HIV L76V 45 49 PR;PR;PI 50;157;102 58;165;104 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. RESULTS: Among the overall 29,643 sequences analyzed, the prevalence of L76V was 1.50%, while was 5.42% in PI-resistant viruses. 2013 PloS one Abstract HIV L76V 72 76 PI 107 109 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Since 2008 the prevalence of L76V was higher in "non-B"-infected than in B-infected patients each year. 2013 PloS one Abstract HIV L76V 29 33 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The L76V was also associated with a lower number of major PI-RAMs in "non-B" vs B samples (3 vs 4, P = 0.0001), and thus it was more frequent found as single major PI-RAM in "non-B" vs B subtype (10% vs 2%, P = 0.014). 2013 PloS one Abstract HIV L76V 4 8 PI;PI 58;164 60;166 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Accordingly, the triple mutant G330E-R332G-R335G bound purified recombinant HIV-1 capsid tubes less efficiently than the double mutant R332G-R335G did. 2013 Virus research Abstract HIV G330E;R332G;R332G;R335G;R335G 31;37;135;43;141 36;42;140;48;146 Capsid 82 88 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. G330E TRIM5alphaHu also disrupted replication-competent HIV-1 propagation in a human T cell line. 2013 Virus research Abstract HIV G330E 0 5 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Here we use a mutated megaprimer approach to create a mutant library of TRIM5alphaHu v1 and to isolate a mutation at Gly330 (G330E) that inhibits transduction of an HIV-1 vector as efficiently as the previously described mutants at positions Arg332 and Arg335. 2013 Virus research Abstract HIV G330E 125 130 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. In a structural model of the TRIM5alphaHu PRYSPRY domain, the addition of G330E to the double mutant R332G-R335G caused extensive changes to the capsid-binding surface, which may explain why the triple mutant was no more restrictive than the double mutant. 2013 Virus research Abstract HIV G330E;R332G;R335G 74;101;107 79;106;112 Capsid 145 151 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Interestingly, G330E did not enhance restriction of HIV-1 when combined with mutations at Arg332 or Arg335. 2013 Virus research Abstract HIV G330E 15 20 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Furthermore, E137K enhanced viral replication kinetics and restored binding affinity with N-HR containing N43D, indicating that it acts as a secondary, compensatory mutation. 2013 The international journal of biochemistry & cell biology Abstract HIV E137K;N43D 13;106 18;110 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. However, when starting with HIV-1N43D/S138A, L33S and I69L emerged in N-HR, and E137K in C-HR. 2013 The international journal of biochemistry & cell biology Abstract HIV N43D;E137K;I69L;L33S;S138A 33;80;54;45;38 37;85;58;49;43 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. T-20 (enfuvirtide) resistance is caused by the N43D primary resistance mutation at its presumed binding site at the N-terminal heptad repeat (N-HR) of gp41, accompanied by the S138A secondary mutation at the C-terminal HR of gp41 (C-HR). 2013 The international journal of biochemistry & cell biology Abstract HIV N43D;S138A 47;176 51;181 gp41;gp41 151;225 155;229 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. T-20E137K/S138A retained activity to HIV-1 without L33S, which seems to be a key mutation for T-20 derivatives. 2013 The international journal of biochemistry & cell biology Abstract HIV E137K;L33S;S138A 4;51;10 9;55;15 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. To determine how HIV-1 in turn escapes T-20S138A we used a dose escalation method to select T-20S138A-resistant HIV-1 starting with either wild-type (HIV-1WT) or T-20-resistant (HIV-1N43D/S138A) virus. 2013 The international journal of biochemistry & cell biology Abstract HIV N43D;S138A;S138A 183;96;188 187;101;193 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We found that when starting with WT background, I37N and L44M emerged in the N-HR of gp41, and N126K in the C-HR. 2013 The international journal of biochemistry & cell biology Abstract HIV I37N;L44M;N126K 48;57;95 52;61;100 gp41 85 89 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We have discovered that modifying T-20 to include S138A (T-20S138A) allows it to efficiently block wild-type and T20-resistant viruses, by a mechanism that involves improved binding of T-20S138A to the N-HR that contains the N43D primary mutation. 2013 The international journal of biochemistry & cell biology Abstract HIV N43D;S138A 225;50 229;55 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We therefore introduced E137K into T-20S138A (T-20E137K/S138A) and revealed that T-20E137K/S138A moderately suppressed replication of T-20S138A-resistant HIV-1. 2013 The international journal of biochemistry & cell biology Abstract HIV E137K;E137K;S138A;E137K;S138A;S138A 50;85;138;24;56;91 55;90;143;29;61;96 23361642 Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses. Primary rilpivirine RAMs were infrequent (4.6%, n=79) and the most prevalent were E138A (3%, n=52), E138K, (0.3%, n=5), H221Y (0.3%, n=5), E138G (0.2%, n=4) and Y181C (0.2%, n=4). 2013 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138G;E138K;H221Y;Y181C 82;139;100;120;161 87;144;105;125;166 23361642 Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses. The common V179I, V189I and V90I polymorphisms have not been associated with virological failure in Phase 3 clinical studies. 2013 The Journal of antimicrobial chemotherapy Abstract HIV V179I;V189I;V90I 11;18;28 16;23;32 23361642 Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses. The other potential rilpivirine-associated mutations that were most prevalent were V179I (8.4%, n=145), V90I (3.8%, n=65) and V189I (2.3%, n=40). 2013 The Journal of antimicrobial chemotherapy Abstract HIV V179I;V189I;V90I 83;126;104 88;131;108 23361642 Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses. The prevalence of K103N was 2% (35/1729). 2013 The Journal of antimicrobial chemotherapy Abstract HIV K103N 18 23 23361642 Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses. The prevalence of K65R and M184I/V was 0.06% (1/1729) and 1% (18/1729), respectively. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184I;M184V 18;27;27 22;34;34 23361642 Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses. We also studied the M184V/I and K65R mutations for emtricitabine and tenofovir, respectively. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184I;M184V 32;20;20 36;27;27 23361642 Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses. We studied the primary rilpivirine RAMs (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L) and other potential rilpivirine-associated mutations (V90I, L100I, K101T, E138S, V179D/I, Y188L, V189I, G190A/E/S and M230V). 2013 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;E138S;F227C;G190A;G190E;G190S;H221Y;K101E;K101P;K101T;L100I;M230I;M230L;M230V;V179D;V179I;V179L;V189I;V90I;Y181C;Y181I;Y181V;Y188L 50;50;50;50;50;183;90;213;213;213;83;41;41;176;169;100;100;227;190;190;65;206;163;72;72;72;199 63;63;63;63;63;188;95;222;222;222;88;48;48;181;174;107;107;232;197;197;70;211;167;81;81;81;204 23363916 [Mutation of drug resistant gene in HIV/AIDS patients with antiretroviral therapy in Shandong province in 2011]. Drug resistance rates of nucleotide reverse transcriptase inhibitor (NRTI) and non-NRTI(NNRTI) were 2.4% (18/742) and 3.0% (22/742), respectively, and the primary mutation types of drug resistance were M184V and Y181C for NRTI and NNRTI, with no resistance to protease inhibitor (PI). 2012 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV M184V;Y181C 202;212 207;217 RT;NNRTI;PR;NNRTI;NNRTI;NRTI;NRTI;PI 36;79;260;88;231;69;222;280 57;87;268;93;236;73;226;282 23364785 Evaluation of etravirine resistance in clinical samples by a simple phenotypic test. Five NNRTI resistant mutant forms of RT were produced (L100I, K103N, L100I/K103N, Y181C, V179D) in order to validate the assay for ETR. 2013 Journal of medical virology Abstract HIV K103N;K103N;L100I;L100I;V179D;Y181C 62;75;55;69;89;82 67;80;60;74;94;87 NNRTI;RT 5;37 10;39 23364785 Evaluation of etravirine resistance in clinical samples by a simple phenotypic test. In the plasma virus from treatment experienced patients with Y181C, A98G, V108I, and/or K101E mutations in the pol gene, higher IC(50) values were found in line with reduced susceptibility data for ETR. 2013 Journal of medical virology Abstract HIV A98G;K101E;V108I;Y181C 68;88;74;61 72;93;79;66 Pol 111 114 23365420 Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins. The majority (20/29) of mutations reduced RC by more than the benchmark M184V antiretroviral drug resistance mutation, with impacts ranging from 8% to 69%. 2013 Journal of virology Abstract HIV M184V 72 77 23365446 Structural and thermodynamic basis of amprenavir/darunavir and atazanavir resistance in HIV-1 protease with mutations at residue 50. Analysis of the crystal structures showed that the substitutions at residue 50 affect how APV, DRV, and ATV bind the protease with altered van der Waals interactions and that the selection of I50V versus I50L is greatly influenced by the chemical moieties at the P1 position for APV/DRV and the P2 position for ATV. 2013 Journal of virology Abstract HIV I50L;I50V 204;192 208;196 PR 117 125 23365446 Structural and thermodynamic basis of amprenavir/darunavir and atazanavir resistance in HIV-1 protease with mutations at residue 50. Reduced affinity to both I50V/A71V and I50L/A71V double mutants is largely due to decreased binding entropy, which is compensated for by enhanced enthalpy for ATV binding to I50V variants and APV binding to I50L variants, leading to hypersusceptibility in these two cases. 2013 Journal of virology Abstract HIV A71V;A71V;I50L;I50L;I50V;I50V 30;44;39;207;25;174 34;48;43;211;29;178 23365446 Structural and thermodynamic basis of amprenavir/darunavir and atazanavir resistance in HIV-1 protease with mutations at residue 50. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. 2013 Journal of virology Abstract HIV I50L;I50V 106;4 110;8 23365446 Structural and thermodynamic basis of amprenavir/darunavir and atazanavir resistance in HIV-1 protease with mutations at residue 50. Thus, the varied inhibitor susceptibilities of I50V/L protease variants are largely a direct consequence of the interdependent changes in protease inhibitor interactions. 2013 Journal of virology Abstract HIV I50L;I50V 47;47 53;53 PR;PR 54;138 62;146 23365446 Structural and thermodynamic basis of amprenavir/darunavir and atazanavir resistance in HIV-1 protease with mutations at residue 50. To explain how APV, DRV, and ATV susceptibility are influenced by mutations at residue 50 in HIV-1 protease, structural and binding thermodynamics studies were carried out on I50V/L-substituted protease variants in the compensatory mutation A71V background. 2013 Journal of virology Abstract HIV A71V;I50L;I50V 241;175;175 245;181;181 PR;PR 99;194 107;202 23365446 Structural and thermodynamic basis of amprenavir/darunavir and atazanavir resistance in HIV-1 protease with mutations at residue 50. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. 2013 Journal of virology Abstract HIV I50L;I50V 31;31 37;37 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Functional assays showed that envelopes with V3 S11R or D25K mutation were dual-tropic, infecting CD4+ target cells that expressed either the CCR5 or CXCR4 coreceptor. 2013 Retrovirology Abstract HIV D25K 56 60 Env 30 39 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. V3 loop envelop glycoprotein gp120 sequence changes that are predictive of a CXCR4 (X4)-using phenotype in HIV-1 subtype B primary isolates, specifically basic amino acid substations at positions 11 (S11R), 24 (G24R) and 25 (D25K) of the loop were detected in the two infected macaques. 2013 Retrovirology Abstract HIV D25K;G24R;S11R 225;211;200 229;215;204 gp120 29 34 23372110 Prevalence of primary resistance mutations to integrase inhibitors in treatment-naive and -experienced patients infected with B and non-B HIV-1 variants. According to the geno2pheno algorithm, some of the secondary mutations detected (L74V, E138K, G163RS, and V151I) have been associated with a reduced estimated susceptibility to RAL and only the E138K mutation has been associated with a decreased estimated susceptibility to EGV. 2013 HIV clinical trials Abstract HIV E138K;E138K;G163R;G163S;L74V;V151I 87;194;94;94;81;106 92;199;100;100;85;111 23372113 HIV-1 drug resistance and associated factors among adults failing first-line highly active antiretroviral therapy in Ho Chi Minh City, Vietnam. Among 87 participating individuals with VL >=1,000 copies/mL, 11 people still harbored a wild-type strain, while 76 participants harbored a HIV-1 drug-resistant strain (2 of which were against protease inhibitors); common DRMs were M184I/V (74%), Y181I/C/V (39%), G190A/S (32%), T215Y/F (32%), and K103N (31%). 2013 HIV clinical trials Abstract HIV G190A;G190S;K103N;M184I;M184V;T215F;T215Y;Y181C;Y181I;Y181V 264;264;298;232;232;279;279;247;247;247 271;271;303;239;239;286;286;256;256;256 PR 193 201 23372113 HIV-1 drug resistance and associated factors among adults failing first-line highly active antiretroviral therapy in Ho Chi Minh City, Vietnam. The proportions of K65R, Q151M, and T69 insertion were 13%, 11%, and 5%, respectively. 2013 HIV clinical trials Abstract HIV K65R;Q151M 19;25 23;30 23376188 How conformational changes can affect catalysis, inhibition and drug resistance of enzymes with induced-fit binding mechanism such as the HIV-1 protease. A comparison to experimental data for the non-active-site mutation L90M of the HIV-1 protease indicates that the mutation slightly destabilizes the closed conformation of the enzyme. 2013 Biochimica et biophysica acta Abstract HIV L90M 67 71 PR 85 93 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. 2013 Journal of medicinal chemistry Abstract HIV V370A 84 89 SP1;Gag 165;161 168;164 23386260 Subtype-specific differences in the development of accessory mutations associated with high-level resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Codon changes K43E, E44D and V118I were found to have no effect on susceptibility to three NRTIs with or without TAMs in either subtype; however, some accessory mutations had subtype-specific effects on viral infectivity. 2013 The Journal of antimicrobial chemotherapy Abstract HIV E44D;K43E;V118I 20;14;29 24;18;34 NRTI 91 96 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. In 80% of isolates piM36I was detected, while rtM184V was detected in 70% of the isolates and was associated with cross-resistance to at least two nucleoside RT inhibitors (NRTI). 2012 Annals of Saudi medicine Abstract HIV M36I 19 25 NRTI;PI;RT;RT 173;19;46;158 177;21;48;160 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. Mutations M36I and M184V were more frequent for PIs, NRTIs and NNRTIs. 2012 Annals of Saudi medicine Abstract HIV M184V;M36I 19;10 24;14 NNRTI;NRTI;PI 63;53;48 69;58;51 23396856 Frequency of amino acid changes associated with resistance to attachment inhibitor BMS-626529 in R5- and X4-tropic HIV-1 subtype B. RESULTS: The M426L substitution associated with a reduced efficacy of the attachment inhibitor BMS-626529 was present at 7.3%. 2013 The Journal of antimicrobial chemotherapy Abstract HIV M426L 13 18 23401688 Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil. Seventy-six percent of genomes (13/17) with TDR carried a nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation, mostly K103N/S (9/13, 69%), potentially compromising the preferential first-line therapy suggested by the Brazilian HIV Treatment Guideline that recommends efavirenz-based combinations. 2013 Advances in virology Abstract HIV K103N;K103S 140;140 147;147 NNRTI;NNRTI 58;105 93;110 23404750 Computational studies identifying entry inhibitor scaffolds targeting the Phe43 cavity of HIV-1 gp120. Inactivity of all the identified hits toward a mutant (Met475Ile) strain strongly suggests that they interact in the Phe43 cavity of gp120, as intended. 2013 ChemMedChem Abstract HIV M475I 55 64 gp120 133 138 23409798 HIV type-1 group O infection in Gabon: low prevalence rate but circulation of genetically diverse and drug-resistant HIV type-1 group O strains. After full-length genome sequencing of these two strains, we found a wide range of natural polymorphism in the protease (>=15 substitutions) and gp41 (N42D mutation) genes, as well as in the gag and gag-pol cleavage sites. 2013 AIDS research and human retroviruses Abstract HIV N42D 151 156 PR;GagPol;gp41;Gag 111;199;145;191 119;206;149;194 23409798 HIV type-1 group O infection in Gabon: low prevalence rate but circulation of genetically diverse and drug-resistant HIV type-1 group O strains. M41L, M184V, and T215Y mutations were also found for one strain, making it resistant to all NRTIs by the Stanford algorithm. 2013 AIDS research and human retroviruses Abstract HIV M184V;T215Y;M41L 6;17;0 11;22;4 NRTI 92 97 23409798 HIV type-1 group O infection in Gabon: low prevalence rate but circulation of genetically diverse and drug-resistant HIV type-1 group O strains. These two strains harbored the Y181C mutation making them resistant to NNRTIs. 2013 AIDS research and human retroviruses Abstract HIV Y181C 31 36 NNRTI 71 77 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. E138K is the most important mutation associated with resistance against rilpivirine and its development must be avoided whenever possible, because this mutation confers broad cross-resistance against all approved members of the non-nucleoside reverse transcriptase inhibitor family of drugs. 2013 HIV/AIDS (Auckland, N.Z.) Abstract HIV E138K 0 5 NNRTI 228 264 23416260 Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). 2013 Infection, genetics and evolution Abstract HIV K103N;M184V;M41L;T215Y 95;77;63;44 100;82;67;53 Rev 50 53 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. CONCLUSIONS: Since H51Y and R263K may define a unique resistance pathway to dolutegravir, our results are consistent with the absence of resistance mutations in antiretroviral drug-naive patients treated with this drug. 2013 Retrovirology Abstract HIV H51Y;R263K 19;28 23;33 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. During previous in vitro selection study, we identified a R263K mutation as the most common substitution to arise in the presence of dolutegravir with H51Y arising as a secondary mutation. 2013 Retrovirology Abstract HIV H51Y;R263K 151;58 155;63 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. RESULTS: We now show that H51Y in combination with R263K increases resistance to dolutegravir but is accompanied by dramatic decreases in both enzymatic activity and viral replication. 2013 Retrovirology Abstract HIV H51Y;R263K 26;51 30;56 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. K102Y, T216M) and HIV Protease (e.g. 2013 PLoS computational biology Abstract HIV T216M;K102Y 7;0 12;5 PR 22 30 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Q18N, N88G) from our dataset. 2013 PLoS computational biology Abstract HIV N88G;Q18N 6;0 10;4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. In therapy-naive individuals, hypermutated proviral DNA with M184I and M230I mutations due to the editing of hA3G, had stop codons in the open reading frames and the same mutations were absent in the plasma virus. 2013 Journal of the International AIDS Society Abstract HIV M184I;M230I 61;71 66;76 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. It is unlikely that viral variants, which exhibit hypermutated sequences and M184I and/or M230I, will mature and expand in vivo. 2013 Journal of the International AIDS Society Abstract HIV M184I;M230I 77;90 82;95 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In M13mp2 lacZalpha-based forward mutation assays, HIV-1 group M (BH10) and group O RTs bearing substitutions D443N, E478Q, V75I/D443N or V75I/E478Q showed 2.0- to 6.6-fold increased accuracy in comparison with the corresponding wild-type enzymes. 2013 Nucleic acids research Abstract HIV D443N;D443N;E478Q;E478Q;V75I;V75I 110;129;117;143;124;138 115;134;122;148;128;142 RT 84 87 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The effects on frameshift fidelity were similar to those reported for mutation E89G and suggest that in HIV-1 group O RT, RNase H inactivation could affect template/primer slippage. 2013 Nucleic acids research Abstract HIV E89G 79 83 RT 118 120 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. We have investigated the effects of substituting Asn for Asp(443) or Gln for Glu(478) on the fidelity of DNA-dependent DNA synthesis of phylogenetically diverse HIV-1 RTs. 2013 Nucleic acids research Abstract HIV D443N;E478Q 49;69 65;85 Asp;RT 57;167 60;170 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. CONCLUSIONS: Our study shows that V86M de-couples the two functions associated with CA-CypA binding. 2013 Retrovirology Abstract HIV V86M 34 38 Capsid 84 86 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Finally, qPCR experiments show that V86M increases HIV-1 transport to the nucleus of cells expressing restrictive TRIM5alpha. 2013 Retrovirology Abstract HIV V86M 36 40 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, V86M does not seem to relieve restriction of a spreading HIV-1 infection by TRIM5alphahu mutants, underscoring context-specific restriction mechanisms. 2013 Retrovirology Abstract HIV V86M 9 13 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, V86M HIV-1 does not seem to be resistant to R332G-R335G TRIM5alphahu in a spreading infection context. 2013 Retrovirology Abstract HIV R332G;R335G;V86M 53;59;9 58;64;13 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. NMR experiments reveal that V86M alters CypA interactions with, and isomerisation of CA. 2013 Retrovirology Abstract HIV V86M 28 32 Capsid 85 87 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. On the other hand, V86M does not affect the CypA-mediated enhancement of HIV-1 replication in permissive human cells. 2013 Retrovirology Abstract HIV V86M 19 23 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Previously, the mutation V86M in the CypA-binding loop of HIV-1 CA was found to be selected upon serial passaging of HIV-1 in cells expressing Rhesus macaque TRIM5alpha (TRIM5alpharh). 2013 Retrovirology Abstract HIV V86M 25 29 Capsid 64 66 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. RESULTS: We find that in single-cycle HIV-1 vector transduction experiments, V86M confers partial resistance against R332G-R335G TRIM5alphahu and other TRIM5alphahu variable 1 region mutants previously isolated in mutagenic screens. 2013 Retrovirology Abstract HIV R332G;R335G;V86M 117;123;77 122;128;81 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Strikingly, restriction of V86M HIV-1 vectors by TRIM5alphahu mutants is mostly insensitive to the presence of CypA in infected cells. 2013 Retrovirology Abstract HIV V86M 27 31 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The objectives of this study were (i) to analyze whether V86M CA allows HIV-1 to escape mutants of TRIM5alphahu, and (ii) to characterize the role of CypA in the resistance to TRIM5alpha conferred by V86M. 2013 Retrovirology Abstract HIV V86M;V86M 57;200 61;204 Capsid 62 64 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M enhances the early stages of HIV-1 replication in restrictive cells by improving nuclear import. 2013 Retrovirology Abstract HIV V86M 0 4 23458243 Sequence variability in p6 gag protein and gag/pol coevolution in human immunodeficiency type 1 subtype F genomes. Also, in our dataset of subtype F genomes a strong association between mutation P5L in the p1/p6 cleavage region of gag and the nelfinavir (NFV) resistance mutation N88D(PR) was found with no impact on the preference for any of the NFV resistance pathways. 2013 AIDS research and human retroviruses Abstract HIV N88D;P5L 165;80 169;83 Gag;Gag;PR 116;94;170 119;96;172 23467175 Evolution and viral characteristics of a long-term circulating resistant HIV-1 strain in a cluster of treatment-naive patients. In vivo evolution showed a mixture with wild-type (T215S/T) in only one untreated patient more than 6 years after diagnosis. 2013 The Journal of antimicrobial chemotherapy Abstract HIV T215S;T215T 51;51 58;58 23467175 Evolution and viral characteristics of a long-term circulating resistant HIV-1 strain in a cluster of treatment-naive patients. We observed eight therapy-naive patients infected with HIV harbouring four mutations at nucleoside reverse transcriptase inhibitor (NRTI) resistance-related positions: M41L, T69S, L210E and T215S. 2013 The Journal of antimicrobial chemotherapy Abstract HIV L210E;M41L;T215S;T69S 180;168;190;174 185;172;195;178 NRTI;NRTI 88;132 120;136 23468492 Identification of an HIV-1 clade A envelope that exhibits broad antigenicity and neutralization sensitivity and elicits antibodies targeting three distinct epitopes. Virus BG505.W6M.ENV.C2 (BG505) was found to have the highest degree of homology (73%) to the MRCA sequence. 2013 Journal of virology Abstract HIV W6M 12 15 Env 16 19 23468492 Identification of an HIV-1 clade A envelope that exhibits broad antigenicity and neutralization sensitivity and elicits antibodies targeting three distinct epitopes. We further showed that a point mutation (L111A) enabled more efficient production of a stable gp120 monomer that preserves the major neutralization epitopes. 2013 Journal of virology Abstract HIV L111A 41 46 gp120 94 99 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Treatment-failing, regimen-stratified subtype-A/AE- and B-patients differed from each other significantly in the frequencies of the major resistance-conferring mutations T215FY, K219QE and several secondary mutations. 2013 PloS one Abstract HIV K219E;K219Q;T215F;T215Y 178;178;170;170 184;184;176;176 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Because the model predicts that the peptide Trp side chain hydrogen bonding with gp120 S375 contributes to the stability of the PT-gp120 complex, we tested this prediction through analysis of peptide binding to gp120 mutant S375A. 2013 Biochemistry Abstract HIV S375A 224 229 gp120;gp120;gp120 81;131;211 86;136;216 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. The results showed that a peptide triazole KR21 inhibits S375A with 20-fold less potency than WT, consistent with predictions of the model. 2013 Biochemistry Abstract HIV S375A 57 62 23480551 Restriction fragment mass polymorphism (RFMP) analysis based on MALDI-TOF mass spectrometry for detecting antiretroviral resistance in HIV-1 infected patients. The concordance rates between the RFMP and direct sequencing assays for the examined codons were 97% (K65R), 97% (T69Ins/D), 97% (L74VI), 97% (K103N), 96% (V106AM), 97% (Q151M), 97% (Y181C), 97% (M184VI) and 94% (T215YF) in the reverse transcriptase coding region, and 100% (D30N), 100% (M46I), 100% (G48V), 100% (I50V), 100% (I54LS), 99% (V82A), 99% (I84V) and 100% (L90M) in the protease coding region. 2013 Clinical microbiology and infection Abstract HIV D30N;G48V;I50V;I54L;I54S;I84V;K103N;K65R;L74I;L74V;L90M;M184I;M184V;M46I;Q151M;T215F;T215Y;V106A;V106M;V82A;Y181C 275;301;314;327;327;352;143;102;130;130;368;196;196;288;170;213;213;156;156;340;183 279;305;318;332;332;356;148;106;135;135;372;202;202;292;175;219;219;162;162;344;188 RT;PR 228;381 249;389 23480640 Subgroup analysis of virological response rates with once- and twice-daily darunavir/ritonavir in treatment-experienced patients without darunavir resistance-associated mutations in the ODIN trial. Virological response (HIV-1 RNA <50 copies/mL) was assessed according to: screening HIV-1 RNA (>= or <50000 copies/mL), CD4 cell count, prior protease inhibitor (PI) use, number of active NRTIs in the OBR, presence of mutations (primary PI mutations, PI RAMs or M184V/I), gender, age, race, HIV-1 clade and adherence. 2013 HIV medicine Abstract HIV M184I;M184V 262;262 269;269 PR;NRTI;PI;PI;PI 142;188;162;237;251 150;193;164;239;253 23517497 Short communication: high rates of thymidine analogue mutations and dual-class resistance among HIV-infected Ugandan children failing first-line antiretroviral therapy. M184V was identified as the only NRTI mutation in 27% (95% CI 15-43%). 2013 AIDS research and human retroviruses Abstract HIV M184V 0 5 NRTI 33 37 23522564 Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled-coil domain regulates 6-helical bundle formation. An artificial salt bridge was added in the 6-helical bundle by substitution of lysine for Ile646. 2013 Bioorganic & medicinal chemistry letters Abstract HIV I646K 79 96 23522564 Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled-coil domain regulates 6-helical bundle formation. With a cholesterol modification at C-terminal, the inhibitor containing I646K mutation represented higher anti-viral activity than C34-cholesterol combination without mutation. 2013 Bioorganic & medicinal chemistry letters Abstract HIV I646K 72 77 2352323 The site of an immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 does not constitute the neutralization epitope. The molecular basis for the resistance was shown to be a point mutation in the env gene, causing the substitution of threonine for alanine at position 582 of gp41. 1990 Journal of virology Abstract HIV A582T 117 154 gp41;Env 158;79 162;82 23525026 HIV-1 drug resistance among newly HIV-1 infected individuals attending tertiary referral center in Chennai, India. K122E (94.4%) and K49R/KR (11.1%) polymorphisms identified in this study have not been previously described in established subtype-C specific polymorphisms. 2011 Indian journal of medical sciences Abstract HIV K49K;K49R;K122E 18;18;0 24;24;5 23525026 HIV-1 drug resistance among newly HIV-1 infected individuals attending tertiary referral center in Chennai, India. RESULTS: Amino acid substitution (K103N and V106MV) at drug resistance positions occurred in two (11%) isolates, conferring high-level resistance to the non-nucleoside reverse-transcriptase inhibitors nevirapine (NVP), efavirenz (EFV), delavirdine (DLV) and notably extensive genetic variations were observed. 2011 Indian journal of medical sciences Abstract HIV K103N;V106M;V106V 34;44;44 40;50;50 NRTI 157 189 23529738 Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Less commonly observed primary IN mutations also showed a range of reduced EVG susceptibilities: 40- to 94-fold for T66K and Q148K and 5- to 10-fold for T66A, E92G, and Q148H. 2013 Antimicrobial agents and chemotherapy Abstract HIV E92G;Q148H;Q148K;T66A;T66K 159;169;125;153;116 163;174;130;157;120 IN 31 33 23529738 Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Primary INSTI resistance-associated mutations (RAMs) at six IN positions have been identified in HIV-1-infected patients failing EVG-containing regimens in clinical studies: T66I/A/K, E92Q/G, T97A, S147G, Q148R/H/K, and N155H. 2013 Antimicrobial agents and chemotherapy Abstract HIV E92G;E92Q;N155H;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;T97A 184;184;220;205;205;205;198;174;174;174;192 190;190;225;214;214;214;203;182;182;182;196 INSTI;IN 8;60 13;62 HIV infections 97 111 23529738 Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Recombinant viruses containing the six most common mutations exhibited a range of reduced EVG susceptibility: 92-fold for Q148R, 30-fold for N155H, 26-fold for E92Q, 10-fold for T66I, 4-fold for S147G, and 2-fold for T97A. 2013 Antimicrobial agents and chemotherapy Abstract HIV E92Q;N155H;Q148R;S147G;T66I;T97A 160;141;122;195;178;217 164;146;127;200;182;221 23529738 Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Some primary IN mutations exhibited broad cross-resistance between EVG and RAL (T66K, E92Q, Q148R/H/K, and N155H), while others retained susceptibility to RAL (T66I/A, E92G, T97A, and S147G). 2013 Antimicrobial agents and chemotherapy Abstract HIV E92G;E92Q;N155H;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;T97A 168;86;107;92;92;92;184;160;160;80;174 172;90;112;101;101;101;189;166;166;84;178 IN 13 15 23529738 Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Susceptibility to DTG was retained by single primary IN mutations but reduced by dual mutation combinations with Q148R. 2013 Antimicrobial agents and chemotherapy Abstract HIV Q148R 113 118 IN 53 55 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. In contrast, plasmids carrying four other mutations (A46V, E80K, Q122H, and S146G) in folP did not similarly confer any sulfonamide resistance to folP-knockout bacteria. 2013 International journal of microbiology Abstract HIV A46V;E80K;Q122H;S146G 53;59;65;76 57;63;70;81 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. Indeed, change of any of the three residues (A37V, N172D, and R193Q) in plasmid-encoded folP diminished the bacterial resistance to sulfonamide while removal of all three mutations abolished the resistance. 2013 International journal of microbiology Abstract HIV A37V;N172D;R193Q 45;51;62 49;56;67 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. Interestingly, cloned folP with three mutations (A37V, N172D, R193Q) derived from Streptococcus mutans 8 conferred substantial resistance against sulfonamide to folP-deficient bacteria. 2013 International journal of microbiology Abstract HIV A37V;N172D;R193Q 49;55;62 53;60;67 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. In rabbit studies the N610Q mutation alone or in combination was associated with an enhanced neutralizing response against homologous and heterologous subtype E viruses. 2013 PloS one Abstract HIV N610Q 22 27 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. One Env, CM243(N610Q), was selected on the basis of studies of the effects of single and multiple mutations of the four gp41 glycosylation sites. 2013 PloS one Abstract HIV N610Q 15 20 gp41;Env 120;4 124;7 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The 14/00/4 Env induced responses superior to CM243(N610Q). 2013 PloS one Abstract HIV N610Q 52 57 Env 12 15 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The single N610Q and N615Q mutations of CM243 Env did not disrupt protein secretion, processing into, or reactivity with mAbs, unlike other single or multiple deglycosylation mutations. 2013 PloS one Abstract HIV N610Q;N615Q 11;21 16;26 Env 46 49 23535575 L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness. However, L100I and K101E reduced the amount of RT in the virions and subsequent addition of L74V restored RT levels back to those of G190S or K103N alone. 2013 The Journal of general virology Abstract HIV G190S;K101E;K103N;L100I;L74V 133;19;142;9;92 138;24;147;14;96 RT;RT 47;106 49;108 23535575 L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness. We conclude that fitness changes caused by L100I, K101E and L74V derive from their effects on RT content. 2013 The Journal of general virology Abstract HIV K101E;L100I;L74V 50;43;60 55;48;64 RT 94 96 23535575 L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness. We found that L100I, K101E and L74V did not change the polymerization or RNase H activities of K103N or G190S RTs. 2013 The Journal of general virology Abstract HIV G190S;K101E;K103N;L100I;L74V 104;21;95;14;31 109;26;100;19;35 RT 110 113 23535575 L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness. We measured the amount of RT in virions and the polymerization and RNase H activities of mutant RTs compared to wild-type, K103N and G190S. 2013 The Journal of general virology Abstract HIV G190S;K103N 133;123 138;128 RT;RT 26;96 28;99 23535575 L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness. We wanted to understand the mechanism by which secondary NNRTI-resistance mutations, L100I and K101E, and the nucleoside resistance mutation, L74V, alter the fitness of K103N and G190S viruses. 2013 The Journal of general virology Abstract HIV G190S;K101E;K103N;L100I;L74V 179;95;169;85;142 184;100;174;90;146 NNRTI 57 62 23540737 Novel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains. The pair of 26-trans enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity index (SI) of 75000, was highly effective against a panel of RTIs-resistant strains with single (Y181C and K103N) or double (A17) mutations in reverse transcriptase. 2013 Journal of medicinal chemistry Abstract HIV K103N;Y181C 209;199 214;205 RT;RT 245;163 266;167 23541840 Detection of HIV-1 minority variants containing the K103N drug-resistance mutation using a simple method to amplify RNA targets (SMART). Finally, SMART probes were used for modeling of K103N concentrations within an unknown sample. 2013 The Journal of molecular diagnostics Abstract HIV K103N 48 53 23541840 Detection of HIV-1 minority variants containing the K103N drug-resistance mutation using a simple method to amplify RNA targets (SMART). The simple method for amplifying RNA targets (SMART) was used to detect K103N, a common HIV-1 reverse transcriptase drug-resistance mutation. 2013 The Journal of molecular diagnostics Abstract HIV K103N 72 77 RT 94 115 23545531 Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series. A recombinant virus encoding the RT W153L was highly resistant to compound A (fold change, 160). 2013 Antimicrobial agents and chemotherapy Abstract HIV W153L 36 41 RT 33 35 23545531 Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series. Compound A also retained full activity against viruses encoding M184V. 2013 Antimicrobial agents and chemotherapy Abstract HIV M184V 64 69 23545531 Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series. In vitro selection for resistant virus to compound A led to the selection of a single substitution within RT: W153L. 2013 Antimicrobial agents and chemotherapy Abstract HIV W153L 110 115 RT 106 108 23545531 Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series. Notably, viruses encoding K65R were hypersusceptible to inhibition by compound A. 2013 Antimicrobial agents and chemotherapy Abstract HIV K65R 26 30 23545531 Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series. The antiviral potency of compound A was unaffected by the presence of nonnucleotide RT inhibitor (NNRTI) mutations tested (L100I, K103N/Y181C, V106A, or Y188L). 2013 Antimicrobial agents and chemotherapy Abstract HIV K103N;L100I;V106A;Y181C;Y188L 130;123;143;136;153 135;128;148;141;158 NNRTI;RT 98;84 103;86 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Interestingly, Vpu variants with a natural S61A mutation showed greater intracellular stability. 2013 PloS one Abstract HIV S61A 43 47 Vpu 15 18 23562659 Improvement of the oligonucleotide ligation assay for detection of the M184V drug-resistant mutation in patients infected with human immunodeficiency virus type 1 subtype CRF01_AE. In this study, an OLA was designed to detect the Methionine to Valine mutation at codon 184 (M184V) of the reverse transcriptase (RT) gene in the circulating recombinant form AE strain of HIV-1 (HIV-1 CRF01_AE) common in Thailand, and was evaluated in Thai patients experiencing treatment failure. 2013 Journal of virological methods Abstract HIV M184V;M184V 93;49 98;91 RT;RT 107;130 128;132 23562659 Improvement of the oligonucleotide ligation assay for detection of the M184V drug-resistant mutation in patients infected with human immunodeficiency virus type 1 subtype CRF01_AE. The OLA-CRF01_AE also detected M184V mutations in 2.4% (1/42) of specimens that were not detected by sequencing. 2013 Journal of virological methods Abstract HIV M184V 31 36 23562659 Improvement of the oligonucleotide ligation assay for detection of the M184V drug-resistant mutation in patients infected with human immunodeficiency virus type 1 subtype CRF01_AE. The subtype-specific OLA-CRF01_AE proved superior to OLA-ARRRP in detecting M184V, although this mutation existed in the genome of the multiple-drug-resistant virus at lower minimal detection levels of 3% prevalence of mutated virus, compared to 50% for OLA-ARRRP. 2013 Journal of virological methods Abstract HIV M184V 76 81 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Here, we show that accumulation of mutations in a drug-resistant HIV-1 protease (HIV-1 PR) variant, D30N/M36I/A71V, changes the fractional occupancy of the equilibrium conformational sampling ensemble. 2013 Biochemistry Abstract HIV A71V;D30N;M36I 110;100;105 114;104;109 PR;PR 71;87 79;89 23571535 Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal: implications for second-line therapy. Common protease substitutions included V10I, V47A, I54M, V71I, I82F, I84V, L90M, and L99F, and most patients harbored viruses containing multiple changes. 2013 Antimicrobial agents and chemotherapy Abstract HIV I54M;I82F;I84V;L90M;L99F;V10I;V47A;V71I 51;63;69;75;85;39;45;57 55;67;73;79;89;43;49;61 PR 7 15 23571535 Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal: implications for second-line therapy. In addition, the triple mutant that included I54M plus I84V plus L90M was resistant to all three PIs (31-, 10-, and 3.8-fold increases in the mean EC50 for darunavir, saquinavir, and lopinavir, respectively). 2013 Antimicrobial agents and chemotherapy Abstract HIV I54M;I84V;L90M 45;55;65 49;59;69 PI 97 100 23571535 Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal: implications for second-line therapy. Relative to wild-type HIV-2, the V47A mutant was resistant to lopinavir (6.3-fold increase in the mean 50% effective concentration [EC50]), the I54M variant was resistant to darunavir and lopinavir (6.2- and 2.7-fold increases, respectively), and the L90M mutant was resistant to saquinavir (3.6-fold increase). 2013 Antimicrobial agents and chemotherapy Abstract HIV I54M;L90M;V47A 144;251;33 148;255;37 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). Major mutations in reverse transcriptase included K65R(n = 1), L74I(n = 1), K103N(n = 19), V106M(n = 4), Y181C(n = 2), M184V(n = 4), and K219E/R(n = 2). 2013 PloS one Abstract HIV K103N;K219E;K219R;K65R;L74I;M184V;V106M;Y181C 76;137;137;50;63;119;91;105 81;144;144;54;67;124;96;110 RT 19 40 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). Major PI-resistance mutations were rare: M46L(n = 1) and I85V(n = 1). 2013 PloS one Abstract HIV I85V;M46L 57;41 61;45 PI 6 8 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Inhibitors 2 and 3 lose interactions with Arg8' in PR20 relative to the wild-type enzyme because Arg8' shifts to interact with mutated L10F side chain. 2013 Journal of medicinal chemistry Abstract HIV L10F 135 139 PR 51 53 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The overall prevalence of TDR was 14.75%, mainly associated with NRTI resistance (13.11%), TAMs and M184V being the most common mutations. 2013 Journal of medical virology Abstract HIV M184V 100 105 NRTI 65 69 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) in conjunction with the L494I substitution in C5 within the association site. 2013 PLoS pathogens Abstract HIV L494I;T138N 156;116 161;122 gp120 14 19 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons in V1, in conjunction with D601N in the DSR. 2013 PLoS pathogens Abstract HIV D601N;N139I;N139N 198;60;60 203;67;67 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. 2013 PLoS pathogens Abstract HIV K601D 33 38 gp120 55 60 23594266 Differential impact of resistance-associated mutations to protease inhibitors and nonnucleoside reverse transcriptase inhibitors on HIV-1 replication capacity. Regarding the effects of resistance to antiretroviral drugs in salvage therapy, decreased replication capacity was noted with the increasing RAMs to darunavir/ritonavir (p<0.001) and specific RAMs (L100I, K101P, and Y181C/I/V) to etravirine (p<0.001). 2013 AIDS research and human retroviruses Abstract HIV K101P;L100I;Y181C;Y181I;Y181V 205;198;216;216;216 210;203;225;225;225 23598281 Formation of a quaternary complex of HIV-1 reverse transcriptase with a nucleotide-competing inhibitor and its ATP enhancer. In vitro susceptibility measurements with mutant viruses containing amino acid substitutions K70G, V75T, L228R, and K219R in the putative ATP binding pocket revealed unexpectedly a hypersusceptible phenotype with respect to INDOPY-1. 2013 The Journal of biological chemistry Abstract HIV K219R;K70G;L228R;V75T 116;93;105;99 121;97;110;103 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. E138Q/R-containing enzymes and viruses also showed the most marked decrease in susceptibility to ETR by both assays. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138Q;E138R 0;0 7;7 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. Each of the E138A/G/K/Q/R mutations, alone or in combination with M184I, resulted in decreased susceptibility to RPV and etravirine (ETR). 2013 Antimicrobial agents and chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;M184I 12;12;12;12;12;66 25;25;25;25;25;71 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. Impacts of mutations at position E138 (A/G/K/Q/R/V) alone or in combination with M184I in HIV-1 reverse transcriptase (RT) were investigated. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;E138V;M184I 33;33;33;33;33;33;81 51;51;51;51;51;51;86 RT;RT 96;119 117;121 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. The addition of M184I to the E138 mutations did not significantly change the levels of diminution in drug susceptibility. 2013 Antimicrobial agents and chemotherapy Abstract HIV M184I 16 21 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. The E138K/Q/R mutations can compensate for M184I in regard to both enzymatic fitness and viral replication capacity. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;E138Q;E138R;M184I 4;4;4;43 13;13;13;48 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. The favored emergence of E138K over other mutations at position E138, together with M184I, is not due to an advantage in either the level of drug resistance or viral replication capacity but may reflect the fact that E138R and E138Q require two distinct mutations to occur, one of which is a disfavorable G-to-C mutation, whereas E138K requires only a single favorable G-to-A hypermutation. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;E138K;E138Q;E138R;M184I 25;330;227;217;84 30;335;232;222;89 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. These findings indicate that E138R caused the highest level of loss of susceptibility to both RPV and ETR, and, accordingly, E138R should be recognized as an ETR resistance-associated mutation. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138R;E138R 29;125 34;130 23612196 Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. We also determined why E138K is the most prevalent nonnucleoside reverse transcriptase inhibitor mutation in patients failing rilpivirine (RPV) therapy. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K 23 28 NNRTI 51 86 23613794 In vitro HIV-1 evolution in response to triple reverse transcriptase inhibitors & in silico phenotypic analysis. Concentrations of 1 microM 3 TC maintained the M184V mutation, which was associated with intrinsic fitness deficits. 2013 PloS one Abstract HIV M184V 47 52 23613794 In vitro HIV-1 evolution in response to triple reverse transcriptase inhibitors & in silico phenotypic analysis. Parameter estimation indicated that the previously unrecognized mutation L228Q was associated with NVP resistance in some isolates. 2013 PloS one Abstract HIV L228Q 73 78 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. However, in HeLa cells BST-2 knockdown was found to further alleviate the effect of Vpu inactivation on infectivity of L30E mutant. 2013 PloS one Abstract HIV L30E 119 123 Vpu 84 87 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. In the present study, we found that the loss of virus infectivity as a result of envelope (Env) incorporation defect caused by a Gag matrix (MA) mutation (L30E) was significantly alleviated by introducing a start codon mutation in vpu. 2013 PloS one Abstract HIV L30E 155 159 Env;Matrix;Vpu;Env;Gag;Matrix 81;133;231;91;129;141 89;139;234;94;132;143 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Inactivation of Vpu partially restored the Env incorporation defect imposed by L30E substitution in MA. 2013 PloS one Abstract HIV L30E 79 83 Vpu;Env;Matrix 16;43;100 19;46;102 23614718 Importance of polar solvation and configurational entropy for design of antiretroviral drugs targeting HIV-1 protease. For the bound complex PR(I50V)-KNI-10075, an increased polar solvation free energy also contributes to the drug resistance. 2013 The journal of physical chemistry. B Abstract HIV I50V 25 29 PR 22 24 23614718 Importance of polar solvation and configurational entropy for design of antiretroviral drugs targeting HIV-1 protease. On the other hand, we predict that the mutant I84V causes drug resistance against KNI-10075 while KNI-10033 is more potent against the I84V mutant compared to wild-type protease. 2013 The journal of physical chemistry. B Abstract HIV I84V;I84V 46;135 50;139 PR 169 177 23614718 Importance of polar solvation and configurational entropy for design of antiretroviral drugs targeting HIV-1 protease. Our calculations indicate that the mutation I50V causes drug resistance against both inhibitors. 2013 The journal of physical chemistry. B Abstract HIV I50V 44 48 23614999 Prediction of virological response and assessment of resistance emergence to the HIV-1 attachment inhibitor BMS-626529 during 8-day monotherapy with its prodrug BMS-663068. CONCLUSIONS: Nonresponse to BMS-663068 was associated with low baseline susceptibility to BMS-626529 and the presence of M426L. 2013 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M426L 121 126 23615903 The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. Accordingly, WT IN catalytic activities and HIV-1 replication were potently inhibited by ALLINIs, whereas the A128T substitution in IN resulted in significant resistance to the inhibitors both in vitro and in cell culture assays. 2013 The Journal of biological chemistry Abstract HIV A128T 110 115 IN;IN 16;132 18;134 23615903 The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. Consequently, the A128T substitution had only a minor effect on the ALLINI IC50 values for IN-LEDGF/p75 binding. 2013 The Journal of biological chemistry Abstract HIV A128T 18 23 IN 91 93 23615903 The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. Instead, ALLINIs markedly altered the multimerization of IN by promoting aberrant higher order WT (but not A128T) IN oligomers. 2013 The Journal of biological chemistry Abstract HIV A128T 107 112 IN;IN 57;114 59;116 23615903 The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. Selection of viral strains under ALLINI pressure has revealed an A128T substitution in HIV-1 IN as a primary mechanism of resistance. 2013 The Journal of biological chemistry Abstract HIV A128T 65 70 IN 93 95 23615903 The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. The A128T substitution did not affect the hydrogen bonding between ALLINI and IN that mimics the IN-LEDGF/p75 interaction but instead altered the positioning of the inhibitor at the IN dimer interface. 2013 The Journal of biological chemistry Abstract HIV A128T 4 9 IN;IN;IN 78;97;182 80;99;184 23615903 The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. The differential multimerization of WT and A128T INs induced by ALLINIs correlated with the differences in infectivity of HIV-1 progeny virions. 2013 The Journal of biological chemistry Abstract HIV A128T 43 48 IN 49 52 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. In an independent culture, D601H appeared with a deletion in V4 (Thr-394-Trp-395) and a D674N substitution in the MPER, however this MPER mutation was inhibitory to W596L/K601H cell-free virus infectivity. 2013 Retrovirology Abstract HIV D601H;D674N;K601H;W596L 27;88;171;165 32;93;176;170 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Interestingly, the functional boost associated with the addition of D674E to W596L/K601H was not observed for cell-cell fusion where the cell-surface expressed glycoproteins function independently of virion assembly. 2013 Retrovirology Abstract HIV D674E;K601H;W596L 68;83;77 73;88;82 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. RESULTS: The HIV-1AD8 mutant, W596L/K601D, was serially passaged in U87.CD4.CCR5 cells until replication was restored. 2013 Retrovirology Abstract HIV K601D;W596L 36;30 41;35 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The W596L/K601H and W596L/K601H/D674E viruses exhibited greater sensitivity to neutralization by the broadly reactive MPER directed monoclonal antibodies, 2F5 and 4E10, indicating that the reverting mutations increase the availability of conserved neutralization epitopes in the MPER. 2013 Retrovirology Abstract HIV D674E;K601H;W596L;K601H;W596L 32;26;20;10;4 37;31;25;15;9 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Whereas the W596L mutation persisted throughout the cultures, a D601H pseudoreversion in the DSR partially restored cell-free virus infectivity and virion gp120-gp41 association, with further improvements to cell-free virus infectivity following a 2nd-site D674E mutation in the membrane-proximal external region (MPER) of gp41. 2013 Retrovirology Abstract HIV D601H;D674E;W596L 64;257;12 69;262;17 gp120;gp41;gp41 155;161;323 160;165;327 23620062 Natural polymorphisms of HIV-1 subtype-C integrase coding region in a large group of ARV-naive infected individuals. A major drug resistance mutation for raltegravir (RAL) and elvitegravir (EVG), Q148H, was retrieved from one patient and another RAL primary resistance mutation, Y143H, was also retrieved from another patient. 2013 Infection Abstract HIV Q148H;Y143H 79;162 84;167 23620062 Natural polymorphisms of HIV-1 subtype-C integrase coding region in a large group of ARV-naive infected individuals. In the DDE-catalytic motif, only one mutation per site (D64G/D116G/E152K) was found, while a low variability (<1 %) was observed for IN positions interacting with LEDGF/p75. 2013 Infection Abstract HIV D64G;D116G;E152K 55;61;67 60;66;72 IN 133 135 23621421 Prevalence of etravirine (ETR)-RAMs at NNRTI failure and predictors of resistance to ETR in a large Italian resistance database (ARCA). V179I, Y181C and G190A were the most frequent mutations in both groups. 2013 Clinical microbiology and infection Abstract HIV G190A;Y181C;V179I 17;7;0 22;12;5 23629015 Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes. For etravirine, only G190A was more prevalent in B than non-B subtypes, whereas V90I and V179E were more frequent in non-B than B subtypes. 2013 The Journal of antimicrobial chemotherapy Abstract HIV G190A;V179E;V90I 21;89;80 26;94;84 23629015 Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes. For rilpivirine, V108I and Y188I were more frequent in B than non-B subtypes, whereas V90I was more prevalent in non-B subtypes. 2013 The Journal of antimicrobial chemotherapy Abstract HIV V108I;V90I;Y188I 17;86;27 22;90;32 23633402 Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques. These findings highlight the need to closely monitor PrEP efficacy in areas with prevalent K65R. 2013 The Journal of infectious diseases Abstract HIV K65R 91 95 23633402 Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques. We investigated in macaques whether FTC/TDF prevents transmission of a tenofovir-resistant simian/human immunodeficiency virus (SHIV) containing the K65R mutation. 2013 The Journal of infectious diseases Abstract HIV K65R 149 153 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Furthermore, Y470H also led to transporter conformational transitions by affecting zinc modulation of DA uptake and WIN35,428 binding as well as enhancing basal DA efflux. 2013 Journal of neuroimmune pharmacology Abstract HIV Y470H 13 18 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Mutation of tyrosine470 (Y470H) attenuated Tat-induced inhibition of DA transport, implicating the functional relevance of this residue for Tat binding to hDAT. 2013 Journal of neuroimmune pharmacology Abstract HIV Y470H 25 30 Tat;Tat 43;140 46;143 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Y470H reduced the maximal velocity of [3H]DA uptake without changes in the K(m) and IC50 values for DA inhibition of DA uptake but increased DA uptake potency for cocaine and GBR12909, suggesting that this residue does not overlap with the binding sites in hDAT for substrate but is critical for these inhibitors. 2013 Journal of neuroimmune pharmacology Abstract HIV Y470H 0 5 23650275 Discovery of piperidine-linked pyridine analogues as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Many compounds were also found to be active against the frequently observed drug-resistant double mutant (K103N+Y181C) HIV-1 strain. 2013 ChemMedChem Abstract HIV K103N;Y181C 106;112 111;117 23658523 Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes. Since BRD4 is unable to compete for binding to CDK9 carrying S175A, expression of CDK9 carrying the S175A mutation in latently infected cells resulted in a robust Tat-dependent reactivation of the provirus. 2013 PLoS pathogens Abstract HIV S175A;S175A 61;100 66;105 Tat 163 166 23658523 Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes. The phosphomimetic S175D mutation modestly enhanced Tat association with CDK9 while causing a 2-fold disruption in BRD4 association with CDK9. 2013 PLoS pathogens Abstract HIV S175D 19 24 Tat 52 55 23658523 Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes. The S175A mutation reduced CDK9 interactions with Tat by an average of 1.7-fold, but also completely blocked CDK9 association with BRD4. 2013 PLoS pathogens Abstract HIV S175A 4 9 Tat 50 53 23660583 Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay. Known proportions of mutant and wild-type plasmids were used to optimize a multiplex OLA for detection of K103N, Y181C, K65R, and M184V in HIV subtypes B and C, and V106M and G190A in subtype C. 2013 Journal of virological methods Abstract HIV G190A;K103N;K65R;M184V;V106M;Y181C 175;106;120;130;165;113 180;111;124;135;170;118 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. Activity tests of IN variants expressed in E coli showed the consensus IN to be active, while both D64V-variants were devoid of specific activities. 2013 PloS one Abstract HIV D64V 99 103 IN;IN 18;71 20;73 23668660 Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues. As expected, the mutation K65R was found only in the non-TA group (18.5%; P < 0.001). 2013 HIV medicine Abstract HIV K65R 26 30 23668660 Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues. This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non-TA group compared with the ZDV group. 2013 HIV medicine Abstract HIV M184V 208 213 NRTI;NNRTI;NRTI 149;79;193 181;84;197 23678638 HIV-1 drug resistant mutations in chronically infected treatment naive individuals in the pre-ARV era in Nigeria. Ten of the 64 (15.6%) samples with positive PCR had mutations for PR inhibitors (PI) including R8D, I 15V, G16E, M36I, M46L, L63P and H69K, while 5 of 63 harbored RT inhibitor (NRTI/NNRTI); V179I, A98T, V179E and A98S. 2012 African journal of medicine and medical sciences Abstract HIV A98S;A98T;G16E;H69K;I15V;L63P;M36I;M46L;R8D;V179E;V179I 213;197;107;134;100;125;113;119;95;203;190 217;201;111;138;105;129;117;123;98;208;195 NNRTI;NRTI;PI;PR;RT 182;177;81;66;163 187;181;83;68;165 23687186 Structural modifications induced by specific HIV-1 protease-compensatory mutations have an impact on the virological response to a first-line lopinavir/ritonavir-containing regimen. Specifically, the L10V + I13V + L63P + I93L cluster, related to fast virological failure, correlated with a decreased drug affinity for the enzyme in comparison with wild-type (DeltaGmut = -30.0 kcal/mol versus DeltaGwt = -42.3 kcal/mol). 2013 The Journal of antimicrobial chemotherapy Abstract HIV I13V;I93L;L10V;L63P 25;39;18;32 29;43;22;36 23687289 Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%-72%, although the antiretroviral activity of proposed second-line regimens has been preserved. 2013 The Journal of infectious diseases Abstract HIV M184V 91 96 NNRTI 101 106 23687289 Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. 2013 The Journal of infectious diseases Abstract HIV K65R 65 69 23687292 Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. Longer therapy increased the risk of TAMs and Q151M but not K65R. 2013 The Journal of infectious diseases Abstract HIV K65R;Q151M 60;46 64;51 23687292 Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. Mutations with preferential tenofovir activity, >= two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. 2013 The Journal of infectious diseases Abstract HIV Q151M 92 97 23687292 Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. Nevirapine increased the risk of TAMs, K65R, and Q151M. 2013 The Journal of infectious diseases Abstract HIV K65R;Q151M 39;49 43;54 23687292 Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. RESULTS: Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. 2013 The Journal of infectious diseases Abstract HIV K65R;K70E 58;66 62;70 23687292 Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. 2013 The Journal of infectious diseases Abstract HIV K65R;K65R;Q151M 45;91;104 49;95;109 23687293 Resistance at virological failure using boosted protease inhibitors versus nonnucleoside reverse transcriptase inhibitors as first-line antiretroviral therapy--implications for sustained efficacy of ART in resource-limited settings. There was a statistically significant difference in prevalence of K65R when comparing NNRTI (1.3%) with PI (0.67%); absolute weighted difference 1.0% (95% CI, .3-1.7; P = .00447). 2013 The Journal of infectious diseases Abstract HIV K65R 66 70 NNRTI;PI 86;104 91;106 23687293 Resistance at virological failure using boosted protease inhibitors versus nonnucleoside reverse transcriptase inhibitors as first-line antiretroviral therapy--implications for sustained efficacy of ART in resource-limited settings. There was also a significant difference in prevalence of M184V/I between NNRTI and PI (crude unweighted prevalence 3.2% vs 1.4%); difference 1.6% (95% CI 0.1-3.1; P = .0368). 2013 The Journal of infectious diseases Abstract HIV M184I;M184V 57;57 64;64 NNRTI;PI 73;83 78;85 23689710 HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains. A combination of L33S and N43K substitutions in gp41 were required for high resistance to T-20EK. 2013 Antimicrobial agents and chemotherapy Abstract HIV L33S;N43K 17;26 21;30 gp41 48 52 23707381 A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication. Further study demonstrated that HIV-1 carrying an I107T Vif mutation displayed significantly reduced fitness in A3G(+) T cells and PBMCs. 2013 Journal of molecular biology Abstract HIV I107T 50 55 Vif 56 59 23707381 A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication. In particular, a single amino acid change (I107T) in one of the non-functional LTS Vif variants, which has not been previously identified in the Los Alamos databases of vif sequences, was found to be responsible for the lack of anti-A3G activity. 2013 Journal of molecular biology Abstract HIV I107T 43 48 Vif;Vif 83;169 86;172 23707381 A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication. Moreover, co-infecting A3G(+) T cells with both the wild-type and I107T Vif viruses resulted in decreased viral replication. 2013 Journal of molecular biology Abstract HIV I107T 66 71 Vif 72 75 23708678 Surveillance of transmitted HIV drug resistance in antiretroviral-naive patients aged less than 25 years, in Bangkok, Thailand. Of 2 patients with TDR, 1 had K103N and the other had Y181C mutations. 2014 Journal of the International Association of Providers of AIDS Care Abstract HIV K103N;Y181C 30;54 35;59 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience. 2013 The Journal of antimicrobial chemotherapy Abstract HIV I15S;K43T;K70Q;L19T;L63P;L63V;L89I;L89T;L89V;V77I 26;38;52;32;44;44;67;67;67;58 30;42;56;36;50;50;75;75;75;62 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. 2013 The Journal of antimicrobial chemotherapy Abstract HIV I50L;N88S 111;120 115;124 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). 2013 The Journal of antimicrobial chemotherapy Abstract HIV A71V;F53L;I85V;M36I;M46I;V82T 95;89;110;77;83;101 99;93;114;81;87;105 23714781 96-Week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE Phase III trials. In RPV VFs, E138K+M184I remained the most frequent combination. 2013 Antiviral therapy Abstract HIV E138K;M184I 12;18 17;23 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. 2013 Frontiers in microbiology Abstract HIV Q733X 35 43 gp41;Env 94;136 98;139 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. Transmitted drug-resistance (TDR) rate among naive patients attended in Spain (n = 144) was 4.7%: 3.4% for PI (all with M46IL), 1.8% for NRTI (all with M184V) and 0.9% for NNRTI (Y188L). 2013 PloS one Abstract HIV M184V;M46I;M46L;Y188L 152;120;120;179 157;125;125;184 NNRTI;NRTI;PI 172;137;107 177;141;109 23720723 Replication fitness of multiple nonnucleoside reverse transcriptase-resistant HIV-1 variants in the presence of etravirine measured by 454 deep sequencing. Using this method, we show that the Y181V mutation in the HIV-1 reverse transcriptase in particular confers a clear selective advantage to the virus over 14 other NNRTI resistance mutations in the presence of etravirine in vitro. 2013 Journal of virology Abstract HIV Y181V 36 41 RT;NNRTI 64;163 85;168 23722251 Virological failure and drug resistance during first line anti-retroviral treatment in Indonesia. Of these failing patients 16 (47%) subjects had drug resistance mutations, predominantly M184V (35.3%), Y181C (23.5%), K103N (11.7%), and TAMs (11.7%). 2013 Journal of medical virology Abstract HIV K103N;M184V;Y181C 119;89;104 124;94;109 23731270 Transmission network of an HIV type 1 strain with K103N in young Belgian patients from different risk groups. All except one of those sequences were from antiretroviral (ARV)-naive patients at the time of sampling, and 22 had the K103N mutation. 2013 AIDS research and human retroviruses Abstract HIV K103N 120 125 23731270 Transmission network of an HIV type 1 strain with K103N in young Belgian patients from different risk groups. As we recently observed an increase of K103N prevalence among new diagnoses in Belgium, we mined the Belgian national sequence database for homologous sequences. 2013 AIDS research and human retroviruses Abstract HIV K103N 39 44 23733474 Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir. Among Y143A,C,G,H,S viruses, the higher prevalence of Y143C viruses is the result of a lower genetic barrier than that of the Y143A,G,S viruses and a lower resistance barrier than that of the Y143H viruses. 2013 Antimicrobial agents and chemotherapy Abstract HIV Y143A;Y143A;Y143C;Y143C;Y143G;Y143G;Y143H;Y143H;Y143S;Y143S 6;126;6;54;6;126;6;192;6;126 19;135;19;59;19;135;19;197;19;135 23733474 Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir. Here we describe clinical isolates with alternative substitutions at position 143 (Y143A, Y143G, Y143H, and Y143S [Y143A,G,H,S]) that emerge less frequently, and we compare the genotypic and phenotypic profiles of these viruses to Y143C,R viruses to reconcile the preferential selection of Y143C,R variants during RAL treatment. 2013 Antimicrobial agents and chemotherapy Abstract HIV Y143A;Y143A;Y143C;Y143C;Y143G;Y143G;Y143H;Y143H;Y143R;Y143R;Y143S;Y143S 83;115;231;290;90;115;97;115;231;290;108;115 88;126;238;297;95;126;102;126;238;297;113;126 23733474 Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir. In addition, Y143A,C,G,H,S viruses require multiple secondary substitutions to develop large reductions in RAL susceptibility. 2013 Antimicrobial agents and chemotherapy Abstract HIV Y143A;Y143C;Y143G;Y143H;Y143S 13;13;13;13;13 18;26;26;26;26 23733474 Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir. Our observations demonstrate that the RAL resistance profiles of Y143A,G,H,S viruses and their association with specific secondary substitutions are similar to the well-established Y143C profile but distinct from the Y143R profile. 2013 Antimicrobial agents and chemotherapy Abstract HIV Y143A;Y143C;Y143G;Y143H;Y143R;Y143S 65;181;65;65;217;65 76;186;76;76;222;76 23733474 Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir. Y143C,R substitutions in HIV-1 integrase define one of three primary raltegravir (RAL) resistance pathways. 2013 Antimicrobial agents and chemotherapy Abstract HIV Y143C;Y143R 0;0 7;7 IN 31 40 23733474 Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir. Y143R viruses differ from Y143A,C,G,H,S viruses in that Y143R confers a greater reduction in RAL susceptibility as a single substitution, consistent with a lower resistance barrier. 2013 Antimicrobial agents and chemotherapy Abstract HIV Y143A;Y143C;Y143G;Y143H;Y143R;Y143S;Y143R 26;26;26;26;56;26;0 39;39;39;39;61;39;5 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Forty-four participants with VF only continued on their failing first-line regimen; by the end of the study period, 90.9% had M184V, 63.6% had thymidine analogue mutations (TAMs), 34.1% had resistance to tenofovir, and 63.6% had resistance to etravirine. 2013 Journal of the International AIDS Society Abstract HIV M184V 126 131 23749952 Evolution of the K65R, K103N and M184V/I reverse transcriptase mutations in HIV-1-infected patients experiencing virological failure between 2005 and 2010. K65R, K103N and M184V/I mutation frequencies were determined each year. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M184I;M184V;K65R 6;16;16;0 11;23;23;4 23749952 Evolution of the K65R, K103N and M184V/I reverse transcriptase mutations in HIV-1-infected patients experiencing virological failure between 2005 and 2010. OBJECTIVES: To assess the prevalence of the K65R, K103N and M184V/I resistance mutations in the reverse transcriptase (RT) region in HIV-1-infected patients failing antiretroviral-based regimens between the years 2005 and 2010. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K65R;M184I;M184V 50;44;60;60 55;48;67;67 RT;RT 96;119 117;121 HIV infections 133 147 23749952 Evolution of the K65R, K103N and M184V/I reverse transcriptase mutations in HIV-1-infected patients experiencing virological failure between 2005 and 2010. RESULTS: Among 9586 patients failing their antiretroviral-based regimens from 2005 to 2010, the prevalence of K65R tended to decrease (P = 0.054), while K103N and M184V/I mutation frequencies decreased significantly over time (P < 0.001). 2013 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K65R;M184I;M184V 153;110;163;163 158;114;170;170 23749954 The preferential selection of K65R in HIV-1 subtype C is attenuated by nucleotide polymorphisms at thymidine analogue mutation sites. CONCLUSIONS: These results further demonstrate that stavudine can preferentially select for K65R in subtype C virus and also provide a basis for understanding the importance of silent nucleotide polymorphisms in regard to altered HIV drug resistance profiles. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 92 96 23749954 The preferential selection of K65R in HIV-1 subtype C is attenuated by nucleotide polymorphisms at thymidine analogue mutation sites. OBJECTIVES: We recently reported the preferential selection of the K65R resistance mutation in subtype C HIV-1 compared with subtype B and showed the underlying mechanism to be dependent on subtype C-specific silent nucleotide polymorphisms. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 67 71 23749954 The preferential selection of K65R in HIV-1 subtype C is attenuated by nucleotide polymorphisms at thymidine analogue mutation sites. RESULTS: The use of nucleoside/nucleotide reverse transcriptase inhibitors [N(t)RTIs] as single drugs or in combination confirmed the more frequent selection of K65R by multiple N(t)RTIs in a subtype B virus that contained the 64/65 nucleotide polymorphisms of subtype C than in a wild-type subtype B virus. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 161 165 RT;NRTI;NRTI 42;76;178 63;84;186 23749954 The preferential selection of K65R in HIV-1 subtype C is attenuated by nucleotide polymorphisms at thymidine analogue mutation sites. The number of clinical reports demonstrating elevated numbers of K65R nevertheless suggests the existence of factors limiting the increased incidence of K65R mutations. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R;K65R 65;153 69;157 23749954 The preferential selection of K65R in HIV-1 subtype C is attenuated by nucleotide polymorphisms at thymidine analogue mutation sites. Thus, we investigated the contributions of subtype C-specific silent nucleotide polymorphisms at thymidine analogue mutation (TAM) sites 70, 210 and/or 219 that might reduce the previously described preferential selection of K65R in subtype C HIV-1 associated with subtype C-specific nucleotide polymorphisms at sites 64/65. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 225 229 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. CONCLUSIONS: We investigated the role of a novel rare NRTI mutation located at position Lys65 of RT (K65E), found in drug-experienced patients failing on NRTIs. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 101 105 NRTI;NRTI;RT 54;154;97 58;159;99 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. Here, analysing a large database, we report the selection of another rare K65E mutation in patients failing on NRTI-containing regimens. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 74 78 NRTI 111 115 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. In 11 out of 15 cases, tenofovir, abacavir, didanosine or stavudine were present at the time of K65E selection. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 96 100 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. In addition to K65R (n = 395) and K65N (n = 9), another mutation, K65E, was found in 15 patients. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E;K65N;K65R 66;34;15 70;38;19 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. METHODS: Clinical and virological characteristics of patients harbouring the K65E mutation were analysed using a large RT sequence database from treatment-experienced individuals. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 77 81 RT 119 121 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. OBJECTIVES: The HIV reverse transcriptase (RT) mutation K65R confers resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs). 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65R 56 60 NRTI;RT;NRTI;RT 83;20;131;43 118;41;136;45 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. Structural analysis of the K65E RT mutant complex was performed by means of docking simulations. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 27 31 RT 32 34 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. The molecular recognition of RT containing K65E supports evidence for the role of this mutation in resistance to tenofovir. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 43 47 RT 29 31 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. The replication capacity was assessed using viruses harbouring the K65E mutation introduced by site-directed mutagenesis (SDM) in pNL 4-3. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 67 71 23749955 Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. This study should have significant clinical implications, as these findings warn clinicians that other minor substitutions at Lys65 (such as K65E) play a role in NRTI resistance. 2013 The Journal of antimicrobial chemotherapy Abstract HIV K65E 141 145 NRTI 162 166 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. Furthermore, the modes of action of these two compounds against the mutated Y212R, N224H and S217H PFV IN were also predicted. 2013 Bioinformation Abstract HIV N224H;S217H;Y212R 83;93;76 88;98;81 IN 103 105 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. An additional five patients had minority K65R populations identified by allele-specific PCR. 2013 Antiviral therapy Abstract HIV K65R 41 45 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. By sequencing, the K65R was identified in 5 (12%), major non-nucleoside reverse transcriptase inhibitor mutations in 24 (57%) and the M184V/I in 12 (28%) patients. 2013 Antiviral therapy Abstract HIV K65R;M184I;M184V 19;134;134 23;141;141 NNRTI 57 93 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. CONCLUSIONS: These data suggest that the K65R prevalence at virological failure is moderately higher in our subtype C population than some non-subtype C HIV cohorts. 2013 Antiviral therapy Abstract HIV K65R 41 45 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. However, we did not find that the K65R was highly selected in HIV-1 subtype-C-infected patients with up to 6 months of failure of a TDF-containing regimen. 2013 Antiviral therapy Abstract HIV K65R 34 38 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. The K65R was associated with lower HIV RNA at failure (HIV RNA 3.3 versus 4.2 log10 copies/ml) and prior stavudine exposure. 2013 Antiviral therapy Abstract HIV K65R 4 8 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. This subtype is reported to develop the principal TDF resistance mutation in the HIV reverse transcriptase, K65R, with greater propensity than other subtypes. 2013 Antiviral therapy Abstract HIV K65R 108 112 RT 85 106 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. We sought to describe K65R development during TDF use in a cohort of patients infected with subtype C HIV. 2013 Antiviral therapy Abstract HIV K65R 22 26 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. For VCV, I408T increased the IC50 by 2-FC and few mutants showed MPI reduction less than 95%: I408T (94%), L317W/I408T (94%) and V169M/L317W/I408T (94%). 2013 AIDS research and therapy Abstract HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W 141;135;129;9;94;113;107 146;140;134;14;99;118;112 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. MPI reduction was observed for mutants I408T (85%), L317W (95%), V169M/I408T (84%), L317W/I408T (85%) and V169M/L317W/I408T (83%). 2013 AIDS research and therapy Abstract HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W;L317W;V169M 118;112;106;71;39;90;52;84;65 123;117;111;76;44;95;57;89;70 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Mutant I408T showed 4-fold change (FC) increase in the half maximal inhibitory concentration (IC50) to MVC, followed by L317W (1.52-FC), V169M (1.23-FC), V169M/I408T (4-FC) L317W/I408T (3-FC), V169M/L317W (1.30-FC), and V169M/L317W/I408T (3.31-FC). 2013 AIDS research and therapy Abstract HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W;L317W;L317W;V169M;V169M;V169M 232;226;220;160;179;7;199;120;171;137;154;193 237;231;225;165;184;12;204;125;178;142;159;198 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Mutations in gp160 were identified and mutants containing V2 (V169M), V3 (L317W) and V4 (I408T) were constructed. 2013 AIDS research and therapy Abstract HIV I408T;L317W;V169M 89;74;62 94;79;67 gp160 13 18 23775803 Investigating the mutation resistance of nonnucleoside inhibitors of HIV-RT using multiple microsecond atomistic simulations. To this end, we have performed 2-2.4 micros simulations with explicit solvent in an isobaric-isothermal ensemble of six different systems: apo wild-type, apo K103N/Y181C mutant, nevirapine-bound wild-type, nevirapine-bound mutant, rilpivirine-bound wild type, and rilpivirine-bound mutant. 2014 Proteins Abstract HIV K103N;Y181C 158;164 163;169 23782115 Transmitted drug-resistance in human immunodeficiency virus-infected adult population in El Salvador, Central America. All showed only one TDR single-class resistance mutation: M184I (two cases) for NRTI, K101E and K103N for NNRTI and L23I for PI. 2013 Clinical microbiology and infection Abstract HIV K101E;K103N;L23I;M184I 86;96;116;58 91;101;120;63 NNRTI;NRTI;PI 106;80;125 111;84;127 23788482 Mutation covariation of HIV-1 CRF07_BC reverse transcriptase during antiretroviral therapy. Meanwhile, three covariation pairs between three treatment-associated mutations (I132L and M184V for RT and I15V for PR) and three overlapping polymorphisms (L10I, L36M and A71V) for PR were also detected. 2013 The Journal of antimicrobial chemotherapy Abstract HIV A71V;I132L;I15V;L10I;L36M;M184V 173;81;108;158;164;91 177;87;112;162;168;96 PR;PR;RT 117;183;101 119;185;103 23788482 Mutation covariation of HIV-1 CRF07_BC reverse transcriptase during antiretroviral therapy. Twelve significant covariation pairs were found between five treatment-associated mutations (K103N, M184V, Q197K, G190A and Y181C) and nine overlapping polymorphisms (A36E, D39N, Y121H, D123E, R135I, T200A, R277K, L283I and D291E). 2013 The Journal of antimicrobial chemotherapy Abstract HIV A36E;D123E;D291E;D39N;G190A;K103N;L283I;M184V;Q197K;R135I;R277K;T200A;Y121H;Y181C 167;186;224;173;114;93;214;100;107;193;207;200;179;124 171;191;229;177;119;98;219;105;112;198;212;205;184;129 23790378 Protein-mediated antagonism between HIV reverse transcriptase ligands nevirapine and MgATP. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. 2013 Biophysical journal Abstract HIV I63M;L289M;L74M 64;80;70 68;85;74 23792096 Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance. Mutations at residues 32I, L33F, 46I, 47A, I54V, V82A, I84V, and L90M render the protease drug resistant against LPV. 2013 Biochemical and biophysical research communications Abstract HIV I54V;I84V;L33F;L90M;V82A 43;55;27;65;49 47;59;31;69;53 PR 81 89 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. CONCLUSIONS: E138G/A/K can be selected by HLA-B*18-restricted CTLs and confer significant rilpivirine resistance. 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 13;13;13 22;22;22 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. E138G/A/K conferred 5.1-, 7.1-, and 2.7-fold resistance to rilpivirine, respectively. 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 0;0;0 9;9;9 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. E138G/A/K in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) are rilpivirine resistance-associated mutations and can be identified in a few ART-naive patients, although at low frequency. 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 0;0;0 9;9;9 RT;RT 57;80 78;82 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. Here we tested whether E138G/A/K could be selected by HLA-B*18-restricted CTLs. 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 23;23;23 32;32;32 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. RESULTS: The prevalence of E138G/A/K was 21% and 0.37% in 19 and 1088 patients with and without HLA-B*18, respectively (odds ratio, 72.3; P = 4.9 x 10(-25)). 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 27;27;27 36;36;36 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. The CTL response was completely abolished by the substitution of E138G/A/K in the epitope peptide. 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 65;65;65 74;74;74 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. The effect of E138G/A/K on drug susceptibility was determined by constructing recombinant HIV-1 variants. 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 14;14;14 23;23;23 23797286 Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. The optimal epitope containing the 138th position was determined and the impact of E138G/A/K on CTL response was analyzed by epitope-specific CTLs. 2013 Clinical infectious diseases Abstract HIV E138A;E138G;E138K 83;83;83 92;92;92 23798668 In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir. No variations were observed for the Y143R/C (+/-T97A) or N155H variants. 2013 The Journal of antimicrobial chemotherapy Abstract HIV N155H;T97A;Y143C;Y143R 57;48;36;36 62;52;43;43 23798668 In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir. Only Q148H/R variants had a reduced level of susceptibility (FC 5.48-18.64). 2013 The Journal of antimicrobial chemotherapy Abstract HIV Q148H;Q148R 5;5 12;12 23798668 In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir. RESULTS: Y143R single mutants conferred a higher level of raltegravir resistance in macrophages [fold change (FC) 47.7-60.24] compared with CD4+ T cells (FC 9.55-11.56). 2013 The Journal of antimicrobial chemotherapy Abstract HIV Y143R 9 14 23798668 In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir. When compared with raltegravir, none to modest increases in resistance were observed for the Y143R/C pathways. 2013 The Journal of antimicrobial chemotherapy Abstract HIV Y143C;Y143R 93;93 100;100 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Since protein-protein interactions depend on the surface residues, the IID-IN mutants that showed high surface accessibility on IN crystal structures (K71R, K111E, Q137R, D202G, and S147G) were selected for further study. 2013 Retrovirology Abstract HIV D202G;K111E;K71R;Q137R;S147G 171;157;151;164;182 176;162;155;169;187 IN;IN 75;128 77;130 23800338 Relatively high prevalence of drug resistance among antiretroviral-naive patients from Henan, Central China. The unexpectedly high percentage of drug resistance in Henan province is mainly due to the prevalence of minor mutations in the protease and integrase regions, especially A71T/V and L68V/I/IM/LV. 2014 AIDS research and human retroviruses Abstract HIV A71T;A71V;L68I;L68L;L68M;L68V 171;171;182;182;182;182 177;177;194;194;194;194 IN;PR 141;128 150;136 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. BACKGROUND: The K65R substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is the major resistance mutation selected in patients treated with first-line antiretroviral tenofovir disoproxil fumarate (TDF). 2013 Retrovirology Abstract HIV K65R 16 20 RT;RT 81;104 102;106 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. CONCLUSION: We have elucidated the mechanism of K65R HIV hypersusceptibility to EFdA. 2013 Retrovirology Abstract HIV K65R 48 52 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. RESULTS: Here we report that the K65R RT mutation causes hypersusceptibility to EFdA. 2013 Retrovirology Abstract HIV K65R 33 37 RT 38 40 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Under the same conditions K65R HIV was inhibited over 70 times more efficiently by EFdA than TDF. 2013 Retrovirology Abstract HIV K65R 26 30 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We determined the molecular mechanism of this hypersensitivity using enzymatic studies with WT and K65R RT. 2013 Retrovirology Abstract HIV K65R 99 103 RT 104 106 23804564 Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S. D10 virions also had increased amounts of RT compared to K101E+G190S in the NL4-3 backbone. 2013 The Journal of general virology Abstract HIV G190S;K101E 63;57 68;62 RT 42 44 23804564 Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S. In contrast, RTs with the D10 backbone had increased RNase H activity compared to WT and K101E+G190S in the NL4-3 backbone. 2013 The Journal of general virology Abstract HIV G190S;K101E 95;89 100;94 RT 13 16 23804564 Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S. Viruses with the mutant combination K101E+G190S replicated better in the presence of NNRTIs than in the absence of drug. 2013 The Journal of general virology Abstract HIV G190S;K101E 42;36 47;41 NNRTI 85 91 23804564 Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S. We compared a NL4-3 RT with K101E+G190S to a patient-isolate RT sequence D10 with K101E+G190S. 2013 The Journal of general virology Abstract HIV G190S;G190S;K101E;K101E 34;88;28;82 39;93;33;87 RT;RT 20;61 22;63 23804564 Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S. We conclude that the backbone sequence of RT can alter the activities of the NNRTI drug-resistant mutant K101E+G190S, and that identification of the amino acids responsible will aid in understanding the mechanism by which NNRTI drug-resistant mutants alter fitness and NNRTIs stimulate HIV-1 virus replication. 2013 The Journal of general virology Abstract HIV G190S;K101E 111;105 116;110 NNRTI;NNRTI;NNRTI;RT 77;222;269;42 82;227;275;44 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. We found that polymerization activity of a reverse transcriptase (RT) with the E478Q mutation that inactivates the RNase H catalytic site is much more sensitive to efavirenz than wild-type RT, indicating that a functional RNase H attenuates the effectiveness of efavirenz. 2013 Biochemistry Abstract HIV E478Q 79 84 RT;RT;RT 43;66;189 64;68;191 23806135 Prevalence of drug resistance mutations and HIV type 1 subtypes in an HIV type 1-infected cohort in rural Tanzania. In samples from 2009 only K103N (3.3%), M184V, and T215FY (0.8%) were detected. 2013 AIDS research and human retroviruses Abstract HIV K103N;M184V;T215F;T215Y 26;40;51;51 31;45;57;57 23806135 Prevalence of drug resistance mutations and HIV type 1 subtypes in an HIV type 1-infected cohort in rural Tanzania. The prevalence of major DR-SNPs in 2005-2007 in the RT gene was determined: K103N (5.0%), Y181C (2.5%), M184V (2.5%), and G190A (1.7%), and M41L, K65KR, K70KR, and L74LV (0.8%). 2013 AIDS research and human retroviruses Abstract HIV G190A;K103N;K65K;K65R;K70K;K70R;L74L;L74V;M184V;M41L;Y181C 122;76;146;146;153;153;164;164;104;140;90 127;81;151;151;158;158;169;169;109;144;95 RT 52 54 23811015 HIV-1 Tat protein variants: critical role for the cysteine region in synaptodendritic injury. The ability of HIV-1 Tat 1-101 Clades B and C, Tat 1-86 and Tat 1-72 proteins, as well as novel peptides (truncated 47-57, 1-72delta31-61, and 1-86 with a mutation at Cys22) to produce early synaptodendritic injury (24h), relative to later cell death (48h), was examined using cell culture. 2013 Experimental neurology Abstract HIV C22P 164 180 Tat;Tat;Tat 21;47;60 24;50;63 23824793 CD4+ T cells support production of simian immunodeficiency virus Env antibodies that enforce CD4-dependent entry and shape tropism in vivo. CD4 independence and neutralization sensitivity were both conferred by Env amino acid changes E84K and D470N that arose independently in multiple animals, with the latter introducing a potential N-linked glycosylation site within a predicted CD4-binding pocket of gp120. 2013 Journal of virology Abstract HIV D470N;E84K 103;94 108;98 gp120;Env 264;71 269;74 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. Among those with recent infection, the most common RAMs to nucleoside reverse transcriptase inhibitors (NRTIs) were M184I/V and T215D/E/F/I/S/Y (1.1%), to non-NRTIs was Y181C (1.3%), and to PIs was M46I (1.5%). 2013 PloS one Abstract HIV M184I;M184V;M46I;T215D;T215E;T215F;T215I;T215S;T215Y;Y181C 116;116;198;128;128;128;128;128;128;169 123;123;202;143;143;143;143;143;143;174 NRTI;NNRTI;NRTI;PI 59;155;104;190 91;164;109;193 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. K70R (p = 0.016) and M46I (p = 0.026) were found more frequently among recently infected patients. 2013 PloS one Abstract HIV M46I;K70R 21;0 25;4 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. Of patients with chronic infection, T215D/E/F/I/S/Y (0.8%; NRTI), Y181C (0.5%; non-NRTI), and M46I (0.4%; PI) were the most common RAMs. 2013 PloS one Abstract HIV M46I;T215D;T215E;T215F;T215I;T215S;T215Y;Y181C 94;36;36;36;36;36;36;66 98;51;51;51;51;51;51;71 NNRTI;NRTI;PI 79;59;106 87;63;108 HIV infections 17 34 23833185 Genetic barrier to the development of resistance to rilpivirine and etravirine between HIV-1 subtypes CRF02_AG and B. Different predominant codons between the subtypes were observed in 5/12 positions (90, 98, 179, 181 and 227), with an effect on the calculated genetic barrier only at the V179D and V179F codons (2.5 versus 3.5 for V179D, and 2.5 versus 5 for V179F, respectively, for subtype B versus subtype CRF02_AG). 2013 The Journal of antimicrobial chemotherapy Abstract HIV V179D;V179D;V179F;V179F 171;214;181;242 176;219;186;247 23833185 Genetic barrier to the development of resistance to rilpivirine and etravirine between HIV-1 subtypes CRF02_AG and B. Nevertheless, subtype CRF02_AG showed a higher genetic barrier to acquiring mutations V179D and V179F (mutations associated with resistance to etravirine) compared with subtype B, suggesting that it would be more difficult to produce resistance to etravirine in the CRF02_AG subtype than the B subtype. 2013 The Journal of antimicrobial chemotherapy Abstract HIV V179D;V179F 86;96 91;101 23834142 A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. Conformational analysis showed that the protease flaps are increasingly flexible in the I50V complexes. 2013 Journal of chemical information and modeling Abstract HIV I50V 88 92 PR 40 48 23834142 A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. Thermodynamic integration calculations reproduced the experimental data to within1 kcal mol-1 and showed that the I50V mutation results in weaker binding free energies for all analyzed complexes with respect to the WT. 2013 Journal of chemical information and modeling Abstract HIV I50V 114 118 23834142 A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. This computational comparative study contributes toward elucidation of the I50V drug-resistance mechanism in HIV-1 PR. 2013 Journal of chemical information and modeling Abstract HIV I50V 75 79 PR 115 117 23834142 A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. This predicts that I50V may confer low resistance to 3c. 2013 Journal of chemical information and modeling Abstract HIV I50V 19 23 23834142 A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. Upon I50V mutation, the complex binding free energy was weakened by a DeltaDeltaG(TI) of 1.8 kcal mol-1, comparable to the marketed inhibitors. 2013 Journal of chemical information and modeling Abstract HIV I50V 5 9 23834142 A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study. We employed molecular dynamics (MD) calculations and free energy (MM-PBSA and thermodynamic integration) analyses on wild-type (WT) and mutated HIV-1 protease (HIV-1 PR) complexes with darunavir, amprenavir, indinavir, and saquinavir to clarify the mechanism of resistance due to the I50V flap mutation. 2013 Journal of chemical information and modeling Abstract HIV I50V 284 288 PR;PR 150;166 158;168 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Analysis of the E45A CA mutant suggests that initial core opening is independent of complete capsid disassembly. 2013 Retrovirology Abstract HIV E45A 16 20 Capsid;Capsid 93;21 99;23 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. A series of site-directed mutagenesis experiments demonstrated that combinations of V3 mutations are required for HIV-1(JR-FLan) to replicate in the presence of 1 microM maraviroc, and that a T199K mutation in the C2 region increases viral fitness in combination with V3 mutations. 2013 PloS one Abstract HIV T199K 192 197 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. HIV-1(V3-M5) derived from HIV-1(JR-FLan) is a noncompetitive-resistant virus that contains five mutations (I304V/F312W/T314A/E317D/I318V) in the gp120 V3 loop alone. 2013 PloS one Abstract HIV I304V;E317D;F312W;I318V;T314A 107;125;113;131;119 112;130;118;136;124 gp120 145 150 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001), Y115F (10% vs. 0.6%; p<0.001), L74VI (8.5% vs. 1.8%; p<0.001), and K70EGQ (7.8% vs. 0.4%) and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001), Y115F (30% vs 0.6%; p<0.001), and L74VI (56% vs 1.8%; p<0.001). 2013 PloS one Abstract HIV K65R;L74I;L74V;Y115F;L74I;L74V;K70E;K70G;K70Q;K65R;Y115F 176;438;438;404;237;237;272;272;272;375;205 180;443;443;409;241;241;278;278;278;379;210 RT 163 165 23840857 Functional complementation of a model target to study Vpu sensitivity. Taking advantage of the functional complementation of the binding defective (D84K) and fusion defective (L493V) MLV and MLV/GaLV Env mutants, we were able to assay the activity of mixed trimers containing both MLV and GaLV CTDs. 2013 PloS one Abstract HIV D84K;L493V 77;105 81;110 Env 129 132 23847055 Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. 2013 The Journal of infectious diseases Abstract HIV M184V 100 105 23847055 Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). 2013 The Journal of infectious diseases Abstract HIV M184V;N155H 63;118 68;123 IN 99 108 23847055 Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. 2013 The Journal of infectious diseases Abstract HIV M184V 229 234 23847055 Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection. Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1-infected patients (8.2% vs 2.5%; P = .004). 2013 The Journal of infectious diseases Abstract HIV M184V 34 39 HIV infections 111 125 23856772 Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. E138K, a G A mutation in HIV-1 reverse transcriptase (RT), is preferentially selected by etravirine (ETR) and rilpivirine over other substitutions at position E138 that offer greater drug resistance. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K 0 5 RT;RT 31;54 52;56 23856772 Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. E138K, as well as E138G, consistently emerged first during ETR selection experiments, followed by E138A and E138Q; E138R was never selected. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138A;E138G;E138Q;E138R;E138K 98;18;108;115;0 103;23;113;120;5 23856772 Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. Surprisingly, E138K was identified as a tiny minority in 23% of drug-naive subtype B patients, a result confirmed by ultradeep sequencing (UDS). 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K 14 19 23856772 Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. This result could reflect a low fitness cost of E138K; however, E138K was one of the least fit substitutions at codon E138, even after taking into account the deoxynucleoside triphosphate pools of the cells used in competition experiments. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;E138K 48;64 53;69 23856772 Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. We hypothesized that there was a mutational bias for the E138K substitution and designed an allele-specific PCR to monitor the emergence of E138A/G/K/Q/R/V during ETR selection experiments. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138A;E138G;E138K;E138K;E138Q;E138R;E138V 140;140;57;140;140;140;140 155;155;62;155;155;155;155 23863885 Diverse reactivity in microwave-promoted catalyst-free coupling of substituted anilines with ethyl trifluoropyruvate and biological evaluation. More significantly, the activities of oxindoles 3q and 3r to inhibit K103N/Y181C double mutant HIV-1 reverse transcriptase (RT) are probably similar to that of the second-generation nonnucleoside inhibitor HBY 097 by docking calculation. 2013 Organic & biomolecular chemistry Abstract HIV K103N;Y181C 69;75 74;80 RT;RT 101;124 122;126 23863885 Diverse reactivity in microwave-promoted catalyst-free coupling of substituted anilines with ethyl trifluoropyruvate and biological evaluation. The best inhibitory activity against wild-type HIV-1 IIIB was exemplified by trifluoromethyloxindole 3q with an IC50 = 5.8 muM, which also displayed potential activity against Y181C mutant virus with an IC50 = 7.5 muM. 2013 Organic & biomolecular chemistry Abstract HIV Y181C 176 181 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. In four independent dose-escalation studies, the N276D mutation was consistently the only alteration found and it was confirmed to be responsible for resistance to HJ16 by site-directed mutagenesis in envelopes (envs) of the homologous CRF02_AG, as well as of a subtype A and a subtype C primary isolate. 2013 PloS one Abstract HIV N276D 49 54 Env;Env 201;212 210;216 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Remarkably, sensitivity to the CD4bs VRC01 and VRC03 mAbs was increased in the N276D mutated viruses. 2013 PloS one Abstract HIV N276D 79 84 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. The effect of N276D was very selective, as it failed to confer resistance to a range of other entry inhibitors. 2013 PloS one Abstract HIV N276D 14 19 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. Protease mutations with the highest rate of expression were L63P, M361 and L90M. 2010 Boletin de la Asociacion Medica de Puerto Rico Abstract HIV L63P;L90M 60;75 64;79 PR 0 8 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. The reverse transcriptase mutations with the highest frequency of expression were M184V, K103N and D67N. 2010 Boletin de la Asociacion Medica de Puerto Rico Abstract HIV D67N;K103N;M184V 99;89;82 103;94;87 RT 4 25 23883841 HIV-1 subtypes and primary antiretroviral resistance mutations in antiretroviral therapy naive HIV-1 infected individuals in Turkey. The patients had primary antiretroviral resistance mutations to nucleos(t)ide reverse transcriptase (RT) inhibitors (NRTIs) (M41L, T215C, T215D, and K219Q), non-nucleoside RT inhibitors (NNRTIs; K103N), and protease inhibitors (PIs; I47V, G73S). 2013 Japanese journal of infectious diseases Abstract HIV G73S;I47V;K103N;K219Q;M41L;T215C;T215D 239;233;195;149;125;131;138 243;237;200;154;129;136;143 NRTI;PR;NNRTI;NRTI;PI;RT;RT 64;207;187;117;228;101;172 99;215;193;122;231;103;174 23884707 Pyridones as NNRTIs against HIV-1 mutants: 3D-QSAR and protein informatics. CoMFA and CoMSIA based 3D-QSAR of HIV-1 RT wild and mutant (K103, Y181C, and Y188L) inhibitory activities of 4-benzyl/benzoyl pyridin-2-ones followed by protein informatics of corresponding non-nucleoside inhibitors' binding pockets from pdbs 2BAN, 3MED, 1JKH, and 2YNF were analysed to discover consensus features of the compounds for broad-spectrum activity. 2013 Journal of computer-aided molecular design Abstract HIV Y181C;Y188L 66;77 71;82 RT 40 42 23888308 Emergence of drug resistance-associated mutations in HIV-1 subtype C protease gene in north India. Approximately 70% polymorphisms as minor mutations were observed in protease gene, of which 14 distinct amino acids changes were linked to partial DR such as G16E, K20R, M36I, D60E, I62V, L63P, I64M, H69K, T74A/S, V77I, V82I, I85V, L89M, and I93L. 2013 Virus genes Abstract HIV D60E;G16E;H69K;I62V;I64M;I85V;I93L;K20R;L63P;L89M;M36I;T74A;T74S;V77I;V82I 176;158;200;182;194;226;242;164;188;232;170;206;206;214;220 180;162;204;186;198;230;246;168;192;236;174;212;212;218;224 PR 68 76 23888308 Emergence of drug resistance-associated mutations in HIV-1 subtype C protease gene in north India. In three (2.9%) DE patients, major DR-associated mutation at D30 N and M46I positions were detected. 2013 Virus genes Abstract HIV D30N;M46I 61;71 66;75 23891838 Reduced HIV-1 integrase flexibility as a mechanism for raltegravir resistance. Obtaining crystallographic structure information on the Q148H/R, G140S/A primary and secondary mutations has been elusive. 2013 Journal of structural biology Abstract HIV G140A;G140S;Q148H;Q148R 65;65;56;56 72;72;63;63 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Most thymidine analogue mutations (TAMs) and T215 revertants (but not T215F/Y) were found to be highly stable, with NNRTI and PI mutations being relatively less persistent. 2013 The Journal of infectious diseases Abstract HIV T215F;T215Y 70;70 77;77 NNRTI;PI 116;126 121;128 23922365 Targeting of the purine biosynthesis host cell pathway enhances the activity of tenofovir against sensitive and drug-resistant HIV-1. Moreover, the extensive use of ddI and d4T has led to high frequencies of the K65R mutation, further compromising TFV efficacy. 2013 The Journal of infectious diseases Abstract HIV K65R 78 82 23934770 Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. G190E, a mutation that causes high-level nevirapine and efavirenz resistance, also markedly reduced susceptibility to etravirine and rilpivirine. 2014 The Journal of antimicrobial chemotherapy Abstract HIV G190E 0 5 23934770 Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. K101H, E138G, V179F and M230L mutations, associated with reduced susceptibility to etravirine and rilpivirine, were also associated with reduced susceptibility to nevirapine and/or efavirenz. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138G;M230L;V179F;K101H 7;24;14;0 12;29;19;5 23934770 Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. RESULTS: Sixteen mutations at 10 positions were significantly associated with the greatest contribution to reduced phenotypic susceptibility (>=10-fold) to one or more NNRTIs, including: 14 mutations at six positions for nevirapine (K101P, K103N/S, V106A/M, Y181C/I/V, Y188C/L and G190A/E/Q/S); 10 mutations at six positions for efavirenz (L100I, K101P, K103N, V106M, Y188C/L and G190A/E/Q/S); 5 mutations at four positions for etravirine (K101P, Y181I/V, G190E and F227C); and 6 mutations at five positions for rilpivirine (L100I, K101P, Y181I/V, G190E and F227C). 2014 The Journal of antimicrobial chemotherapy Abstract HIV F227C;F227C;G190A;G190A;G190E;G190E;G190E;G190E;G190Q;G190Q;G190S;G190S;K101P;K101P;K101P;K101P;K103N;K103N;K103S;L100I;L100I;V106A;V106M;V106M;Y181C;Y181I;Y181I;Y181I;Y181V;Y181V;Y181V;Y188C;Y188C;Y188L;Y188L 466;558;281;380;281;380;456;548;281;380;281;380;233;347;440;532;240;354;240;340;525;249;249;361;258;258;447;539;258;447;539;269;368;269;368 471;563;292;391;292;391;461;553;292;391;292;391;238;352;445;537;247;359;247;345;530;256;256;366;267;267;454;546;267;454;546;276;375;276;375 NNRTI 168 174 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Phylogenetic analysis of HIV sequences from the child revealed low-diversity variants indicating infection by a subtype C single transmitted/founder virus that shared full-length sequence identity with a clonally-amplified maternal breast milk virus variant harboring the K103N NVP resistance mutation. 2013 Retrovirology Abstract HIV K103N 272 277 23952717 HIV antiretroviral resistance mutations among antiretroviral treatment-naive and -experienced patients in South Korea. Among ART-experienced patients, M184V was the most common mutation. 2013 AIDS research and human retroviruses Abstract HIV M184V 32 37 23952717 HIV antiretroviral resistance mutations among antiretroviral treatment-naive and -experienced patients in South Korea. Among ART-naive patients, V179D was the most common mutation, being found in five ART-naive patients. 2013 AIDS research and human retroviruses Abstract HIV V179D 26 31 23959304 In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. AIC292 also retained activity against viruses harboring NNRTI resistance-associated mutations (RAMs), including the most prevalent variants, K103N, Y181C, and G190A. 2013 Antimicrobial agents and chemotherapy Abstract HIV G190A;K103N;Y181C 159;141;148 164;146;153 NNRTI 56 61 23959304 In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Interestingly, viruses bearing the L100I RAM were hypersusceptible to AIC292. 2013 Antimicrobial agents and chemotherapy Abstract HIV L100I 35 40 23960077 Structural and functional properties of the membranotropic HIV-1 glycoprotein gp41 loop region are modulated by its intrinsic hydrophobic core. Additionally, the K601A, but not the L602A, impaired disulfide bond formation in the peptides. 2013 The Journal of biological chemistry Abstract HIV K601A;L602A 18;37 23;42 23960077 Structural and functional properties of the membranotropic HIV-1 glycoprotein gp41 loop region are modulated by its intrinsic hydrophobic core. Furthermore, two loop core mutations, K601A and L602A, are found to inhibit HIV-1 infectivity while keeping wild type-like levels of the envelope, implying that they exert an inhibitory effect on gp41 during the membrane fusion event. 2013 The Journal of biological chemistry Abstract HIV K601A;L602A 38;48 43;53 Env;gp41 137;196 145;200 23960077 Structural and functional properties of the membranotropic HIV-1 glycoprotein gp41 loop region are modulated by its intrinsic hydrophobic core. In the membrane, however, the L602A, but not the K601A, reduced the lipid mixing ability of the loop peptides, which was correlated with decreased alpha-helical content of the L602A mutant. 2013 The Journal of biological chemistry Abstract HIV K601A;L602A;L602A 49;30;176 54;35;181 23960077 Structural and functional properties of the membranotropic HIV-1 glycoprotein gp41 loop region are modulated by its intrinsic hydrophobic core. This was correlated with changes in the circular dichroism spectrum imposed by the K601A mutation. 2013 The Journal of biological chemistry Abstract HIV K601A 83 88 23960077 Structural and functional properties of the membranotropic HIV-1 glycoprotein gp41 loop region are modulated by its intrinsic hydrophobic core. We show that the K601A mutation, but not the L602A mutation, abolished the binding of a loop-specific monoclonal antibody to a loop domain peptide. 2013 The Journal of biological chemistry Abstract HIV K601A;L602A 17;45 22;50 23966385 Generation of rhesus macaque-tropic HIV-1 clones that are resistant to major anti-HIV-1 restriction factors. First, by sequence- and structure-guided mutagenesis, three amino acid residues in Gag-capsid (CA) (M94L/R98S/G114Q) were found to be responsible for viral growth enhancement in a macaque cell line. 2013 Journal of virology Abstract HIV M94L;G114Q;R98S 100;110;105 104;115;109 Capsid;Gag;Capsid 87;83;95 93;86;97 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. No transmitted HIV-1 drug-resistance mutation was found in 59 ART-naive adults, but K103N and G190S mutations were observed in one ART-naive child. 2013 PloS one Abstract HIV G190S;K103N 94;84 99;89 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. The most prevalent mutation was lamivudine-resistance M184V (n = 12, 38.7%) followed by efavirenz/nevirapine-resistance K103N (n = 9, 29.0%), and zidovudine/stavudine-resistance T215Y/F (n = 6, 19.4%). 2013 PloS one Abstract HIV K103N;M184V;T215F;T215Y 120;54;178;178 125;59;185;185 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. Within the viral protease, the major nelfinavir-resistance mutation L90M was found in one case. 2013 PloS one Abstract HIV L90M 68 72 PR 17 25 23979153 Lack of protease inhibitor resistance following treatment failure--too good to be true? Genotypic resistance testing revealed only an M184V mutation associated with emtricitabine resistance. 2013 The Journal of clinical investigation Abstract HIV M184V 46 51 23979732 In vitro cross-resistance profile of nucleoside reverse transcriptase inhibitor (NRTI) BMS-986001 against known NRTI resistance mutations. In the site-directed mutagenesis studies, a virus containing a K65R substitution exhibited a 0.4-fold change in 50% effective concentration (EC50) versus the wild type, while the majority of viruses with the Q151M constellation (without M184V) exhibited changes in EC50 versus wild type of 0.23- to 0.48-fold. 2013 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V;Q151M 63;237;208 67;242;213 23979732 In vitro cross-resistance profile of nucleoside reverse transcriptase inhibitor (NRTI) BMS-986001 against known NRTI resistance mutations. Susceptibility to BMS-986001 was also maintained in an L74V-containing virus (0.7-fold change), while an M184V-only-containing virus induced a 2- to 3-fold decrease in susceptibility. 2013 Antimicrobial agents and chemotherapy Abstract HIV L74V;M184V 55;105 59;110 23980523 Week 96 analysis of rilpivirine or efavirenz in HIV-1-infected patients with baseline viral load =1000 copies/ml harbored HIVDR (prevalence: 5.3%; 4/76), with M184V/I (4/4) and K103K/N (3/4) being the most prevalent mutations. 2013 PloS one Abstract HIV K103K;K103N;M184I;M184V 107;107;89;89 114;114;96;96 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. RESULTS: At baseline, a prevalence of 3.6% (5/139) HIVDR was observed [protease inhibitors M46I (1/5), G73A (1/5), L90LM (1/5); nucleoside reverse transcriptase inhibitors: M184V (1/5), T215F (1/5); non-nucleoside reverse transcriptase inhibitors: K103N (1/5), Y181Y/C (2/5), M230ML (1/5)]. 2013 PloS one Abstract HIV G73A;K103N;L90L;L90M;M184V;M230L;M230M;M46I;T215F;Y181C;Y181Y 103;248;115;115;173;276;276;91;186;261;261 107;253;120;120;178;282;282;95;191;268;268 NNRTI;NRTI;PR 199;128;71 235;160;79 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. Previous biochemical and virological studies have shown that compensatory interactions between substitutions E138K and M184I can restore enzyme processivity and the viral replication capacity. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;M184I 109;119 114;124 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. Recombinant RT enzymes and viruses containing K101E, but not E138K, were highly resistant to nevirapine (NVP) and delavirdine (DLV) as well as ETR and RPV, but not EFV. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E 61;46 66;51 RT 12 14 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. Resistance to the recently approved nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) commonly involves substitutions at positions E138K and K101E in HIV-1 reverse transcriptase (RT), together with an M184I substitution that is associated with resistance to coutilized emtricitabine (FTC). 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E;M184I 153;163;223 158;168;228 NNRTI;RT;NNRTI;RT 36;178;83;201 71;199;88;203 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. The addition of K101E to E138K slightly enhanced ETR and RPV resistance compared to that obtained with E138K alone but restored susceptibility to NVP and DLV. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;E138K;K101E 25;103;16 30;108;21 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. The coexistence of K101E and E138K does not impair either viral replication or enzyme fitness. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E 29;19 34;24 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. The current study was designed to investigate the impact of K101E, alone or in combination with E138K and/or M184I, on drug susceptibility, viral replication capacity, and enzyme function. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E;M184I 96;60;109 101;65;114 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. The K101E substitution can compensate for deficits in viral replication capacity and enzyme processivity associated with M184I, while M184I can compensate for the diminished efficiency of DNA polymerization associated with K101E. 2013 Antimicrobial agents and chemotherapy Abstract HIV K101E;K101E;M184I;M184I 4;223;121;134 9;228;126;139 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. We conclude that K101E can play a significant role in resistance to RPV. 2013 Antimicrobial agents and chemotherapy Abstract HIV K101E 17 22 24002090 Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors. We show here that K101E can be selected in cell culture by the NNRTIs etravirine (ETR), efavirenz (EFV), and dapivirine (DPV) as well as by RPV. 2013 Antimicrobial agents and chemotherapy Abstract HIV K101E 18 23 NNRTI 63 69 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Mutations such as M184V/I, K103N, V106A, Y181C and G190A were common among the ART-failure individuals, and the frequencies of M184V/I, K103N and V106A were 28.2%, 19.2%, and 22.1%, respectively. 2013 PloS one Abstract HIV G190A;K103N;K103N;M184I;M184I;M184V;M184V;V106A;V106A;Y181C 51;27;136;18;127;18;127;34;146;41 56;32;141;25;134;25;134;39;151;46 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. A likely reason is the elucidation of novel epitopes by L90M. 2013 PloS one Abstract HIV L90M 56 60 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Here it was discovered that an important antiretroviral resistance mutation, L90M in HIV protease, occurs at lower frequencies in hosts that harbor the B*15, B*48 or A*32 human leukocyte antigen subtypes. 2013 PloS one Abstract HIV L90M 77 81 PR 89 97 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. NetMHCPan predictions reveal increased affinity of the peptide spanning the HIV protease region, PR 89-97 and PR 90-99 to HLA-B*15/B*48 and HLA-A*32 respectively due to the L90M substitution. 2013 PloS one Abstract HIV L90M 173 177 PR;PR;PR 80;97;110 88;99;112 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Among these 520 patients, a total of 66 subjects (66/520, 12.7%) presented >= 1 MNR mutation, including Q151M, K65R, and Insert69 for 59 (11.3%), 29 (5.6%), and 2 (0.4%) patients, respectively. 2013 PloS one Abstract HIV K65R;Q151M 111;104 115;109 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. BACKGROUND: Multi-nucleos(t)ide resistance (MNR) mutations including Q151M, K65R mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region may confer resistance to all molecules of nucleos(t)ide reverse transcriptase inhibitors (NRTI). 2013 PloS one Abstract HIV K65R;Q151M 76;69 80;74 NRTI;RT;NRTI 205;127;253 240;148;257 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. In multivariate analysis, both Q151M (p = 0.039) and K65R (p = 0.029) mutations were independently associated with current stavudine- compared to zidovudine-use. 2013 PloS one Abstract HIV K65R;Q151M 53;31 57;36 24025024 Transmitted drug resistance is still low in newly diagnosed human immunodeficiency virus type 1 CRF06_cpx-infected patients in Estonia in 2010. In 2010, 2.5% (6/244) of the sequences harbored nonnucleoside reverse transcriptase inhibitor (NNRTI) (K103N and K101E), 1.6% (4/244) nucleoside reverse transcriptase inhibitor (NRTI) (M41L, M184I, and K219E), and 0.4% (1/244) protease inhibitor (PI) (V82A) mutations. 2014 AIDS research and human retroviruses Abstract HIV K101E;K103N;K219E;M184I;M41L;V82A 113;103;202;191;185;252 118;109;207;196;189;256 NNRTI;NRTI;PR;NNRTI;NRTI;PI 48;134;227;95;178;247 83;166;235;100;182;249 24037943 Polymorphisms in the HIV-1 gp41 env gene, natural resistance to enfuvirtide (T-20) and pol resistance among pregnant Brazilian women. The frequency of natural resistance to T-20 (N42D, L44M, and R46M-low-impact mutations) was 6.1% (6/98); 20.4% (20/98) had compensatory mutations in HR2. 2014 Journal of medical virology Abstract HIV L44M;N42D;R46M 51;45;61 55;49;65 24038219 Trends in prevalence of HIV-1 drug resistance in Thailand 2009-2010. CONCLUSIONS: In 2010, three mutations in PR gene, M36I, H69K, and L90M, were decreased significantly. 2013 Journal of clinical laboratory analysis Abstract HIV H69K;L90M;M36I 56;66;50 60;70;54 PR 41 43 24038219 Trends in prevalence of HIV-1 drug resistance in Thailand 2009-2010. However, only one mutation in RT gene, M41L was significantly increased. 2013 Journal of clinical laboratory analysis Abstract HIV M41L 39 43 RT 30 32 24038219 Trends in prevalence of HIV-1 drug resistance in Thailand 2009-2010. In 2010, M41L was increased significantly from 7.5% to 14.9%. 2013 Journal of clinical laboratory analysis Abstract HIV M41L 9 13 24038219 Trends in prevalence of HIV-1 drug resistance in Thailand 2009-2010. Three sequences in PR gene, M36I, H69K, and L90M, were decreased significantly in 2010 when compared to 2009. 2013 Journal of clinical laboratory analysis Abstract HIV H69K;L90M;M36I 34;44;28 38;48;32 PR 19 21 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. 2013 PloS one Abstract HIV T174I 33 38 RT;IN 151;55 172;57 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. 2013 PloS one Abstract HIV T174I 19 24 IN 139 141 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. K103S was found in two women with no M184V detection. 2013 BMC infectious diseases Abstract HIV M184V;K103S 37;0 42;5 24055077 Towards new C6-rigid S-DABO HIV-1 reverse transcriptase inhibitors: synthesis, biological investigation and molecular modeling studies. A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. 2013 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 231;237 236;242 NNRTI;RT 169;220 175;222 24055802 The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort. 21 cases of K65R were detected over the course of follow up, giving an overall event rate of 0.21 (95% CI: 0.12-0.31)/100 person years follow up (PYFU). 2014 The Journal of infection Abstract HIV K65R 12 16 24055802 The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort. 47 of these episodes were preceded by resistance tests showing development of K65R or M184V mutation and were hence excluded. 2014 The Journal of infection Abstract HIV K65R;M184V 78;86 82;91 24055802 The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort. CONCLUSIONS: We have not found evidence of an increased risk of development of M184V and K65R in patients exposed to 3TC. 2014 The Journal of infection Abstract HIV K65R;M184V 89;79 93;84 24055802 The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort. METHODS: In this study we analysed linked data from the observational UK Collaborative HIV Cohort (CHIC) Study and UK HIV Drug Resistance Database (HDRD) to investigate the rate of development of K65R or M184V resistance mutations in patients failing on combinations containing tenofovir (TDF) and efavirenz (EFV) with either 3TC or FTC. 2014 The Journal of infection Abstract HIV K65R;M184V 196;204 200;209 24055802 The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort. Of those receiving 3TC (n = 53), 7 (13.2%), 12 (22.6%) and 15 (28.3%) developed K65R, M184V and either K65R or M184V respectively. 2014 The Journal of infection Abstract HIV K65R;K65R;M184V;M184V 80;103;86;111 84;107;91;116 24055802 The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort. Of those receiving FTC (n = 148), 13 (8.8%), 20 (13.5%) and 26 (17.6%) developed K65R, M184V and either K65R or M184V respectively. 2014 The Journal of infection Abstract HIV K65R;K65R;M184V;M184V 81;104;87;112 85;108;92;117 24055802 The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort. The overall event rate for detection of M184V was 0.38 (95% CI: 0.26-0.5)/100 PYFU. 2014 The Journal of infection Abstract HIV M184V 40 45 24059291 Short communication: molecular epidemiology of HIV type 1 infection in northern Greece (2009-2010): evidence of a transmission cluster of HIV type 1 subtype A1 drug-resistant strains among men who have sex with men. The main cluster within subtype A1 (I) included eight men reporting having sex with men from Thessaloniki infected with dual-class RT-resistant strains carrying both T215C and Y181C mutations. 2014 AIDS research and human retroviruses Abstract HIV T215C;Y181C 166;176 171;181 RT 131 133 24078120 Stabilization of human immunodeficiency virus type 1 reverse transcriptase by site-directed mutagenesis. The Asp443 Ala mutation, which abolishes RNase H activity, was introduced into the p66 subunits of HIV-1 M RT and HIV-1 O RT. 2013 Biotechnology letters Abstract HIV D443A 4 14 Asp;RT;RT 4;107;122 7;109;124 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Both monomeric PR20(T26A) and dimeric PR20 exhibit Tm values 6-7.5C higher than those for their PR counterparts. 2013 Biochemistry Abstract HIV T26A 20 24 PR;PR;PR 15;38;96 17;40;98 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. However, without other compensatory mutations as seen in PR20, L33F and L63P substitutions, together, neither restrict autoproteolysis nor significantly reduce binding affinity to darunavir. 2013 Biochemistry Abstract HIV L33F;L63P 63;72 67;76 PR 57 59 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. To determine whether dimer stability contributes to binding affinity for inhibitors, we examined single-chain dimers of PR and PR(D25N) in which the corresponding identical monomer units were covalently linked by GGSSG sequence. 2013 Biochemistry Abstract HIV D25N 130 134 PR;PR 120;127 122;129 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Two specific mutations in PR20, L33F and L63P at sites of autoproteolysis, increase the Tm of monomeric PR(T26A) by ~8C, similar to PR20(T26A). 2013 Biochemistry Abstract HIV L33F;L63P;T26A;T26A 32;41;107;137 36;45;111;141 PR;PR;PR 26;104;132 28;106;134 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Homology modeling provided insight into the mechanism of resistance conferred by G118R as well as the effects of H51Y or E138K on enzyme activity. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;G118R;H51Y 121;81;113 126;86;117 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Now, we have characterized the impact of the G118R substitution, alone or in combination with either H51Y or E138K, on 3' processing and integrase strand transfer activity. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;G118R;H51Y 109;45;101 114;50;105 IN 137 146 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. The addition of either of H51Y or E138K to G118R did not enhance resistance to DTG, RAL, or EVG. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;G118R;H51Y 34;43;26 39;48;30 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. The addition of H51Y and E138K to G118R partially restored strand transfer activity by modulating the formation of integrase-LTR complexes through increasing LTR DNA affinity and total DNA binding, respectively. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;G118R;H51Y 25;34;16 30;39;20 IN;LTR;LTR 115;125;158 124;128;161 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. The G118R substitution resulted in low-level resistance to DTG, raltegravir (RAL), and elvitegravir (EVG). 2013 Antimicrobial agents and chemotherapy Abstract HIV G118R 4 9 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. The G118R substitution therefore represents a potential avenue for resistance to DTG, similar to that previously described for the R263K substitution. 2013 Antimicrobial agents and chemotherapy Abstract HIV G118R;R263K 4;131 9;136 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. The results show that G118R primarily impacted the strand transfer step of integration by diminishing the ability of integrase-long terminal repeat (LTR) complexes to bind target DNA. 2013 Antimicrobial agents and chemotherapy Abstract HIV G118R 22 27 LTR;IN;LTR 127;117;149 147;126;152 24080645 Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. We previously used the new INSTI dolutegravir (DTG) to select a G118R integrase resistance substitution in tissue culture and also showed that secondary substitutions emerged at positions H51Y and E138K. 2013 Antimicrobial agents and chemotherapy Abstract HIV E138K;G118R;H51Y 197;64;188 202;69;192 IN;INSTI 70;27 79;32 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. RESULTS: We found that 12 (7.9%) of the 152 successfully sequenced samples harboured primary resistance mutations, of which K103N and G190A were the most prevalent. 2013 Journal of the International AIDS Society Abstract HIV G190A;K103N 134;124 139;129 24109238 Functional antagonism of rhesus macaque and chimpanzee BST-2 by HIV-1 Vpu is mediated by cytoplasmic domain interactions. Importantly, a Vpu mutant carrying two mutations in its transmembrane domain (A14L and W22A), rendering it incompetent for interaction with human BST-2, was able to interact with human BST-2 carrying the rhesus BST-2 cytoplasmic domain and partially neutralized the ability of this BST-2 variant to inhibit viral release. 2013 Journal of virology Abstract HIV A14L;W22A 78;87 82;91 Vpu 15 18 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. Sixty-seven percent virologic failures harbored viruses with>= 1 drug resistant mutations (DRMs); M184V/K103N was the predominant resistance pathway. 2013 BMC infectious diseases Abstract HIV K103N;M184V 104;98 109;103 24122937 Dried blood spots for HIV-1 drug resistance genotyping in decentralized settings in Senegal. M184V/I was the most frequent mutation occurring, followed by K103N. 2014 Journal of medical virology Abstract HIV K103N;M184I;M184V 62;0;0 67;7;7 24127302 Molecular diversity of HIV-1 and surveillance of transmitted drug resistance variants among treatment Naive patients, 5 years after active introduction of HAART in Kuala Lumpur, Malaysia. The commonly detected mutation that may affect current first line therapy was V179D (3%), which may lead to reduced susceptibility to NNRTI. 2014 Journal of medical virology Abstract HIV V179D 78 83 NNRTI 134 139 24128669 Genotypic correlates of susceptibility to HIV-1 attachment inhibitor BMS-626529, the active agent of the prodrug BMS-663068. RESULTS: An M426L or S375M change were the major substitutions associated with reductions in susceptibility to BMS-626529 in baseline samples of subtype B viruses from the monotherapy study, with M434I and M475I contributing to a lesser extent. 2014 The Journal of antimicrobial chemotherapy Abstract HIV M426L;M434I;M475I;S375M 12;196;206;21 17;201;211;26 24132393 F99 is critical for dimerization and activation of South African HIV-1 subtype C protease. Secondary and quaternary structure analysis were performed and revealed that the F99A PR is monomeric with reduced beta-sheet content. 2013 The protein journal Abstract HIV F99A 81 85 PR 86 88 24132393 F99 is critical for dimerization and activation of South African HIV-1 subtype C protease. The F99A PR and wild-type C-SA PR were overexpressed and purified. 2013 The protein journal Abstract HIV F99A 4 8 PR;PR 9;31 11;33 24132393 F99 is critical for dimerization and activation of South African HIV-1 subtype C protease. The F99A PR showed no activity and the inability to bind to the inhibitor. 2013 The protein journal Abstract HIV F99A 4 8 PR 9 11 24145401 Tenascin-C is an innate broad-spectrum, HIV-1-neutralizing protein in breast milk. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by V3 loop- (19B and F39F) and chemokine coreceptor binding site-directed (17B) monoclonal antibodies. 2013 Proc Natl Acad Sci U S A Abstract HIV F39F 145 149 Env 20 28 24145402 Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. The impact of gp120-gp41 cleavage on trimer structure, in the presence or absence of trimer-stabilizing modifications (i.e., a gp120-gp41 disulfide bond and an I559P gp41 change, together designated SOSIP), was assessed. 2013 Proc Natl Acad Sci U S A Abstract HIV I559P 160 165 gp120;gp120;gp41;gp41;gp41 14;127;20;133;166 19;132;24;137;170 24145874 Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study. Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. 2014 Clinical infectious diseases Abstract HIV L90M;L90M 63;96 67;100 24145874 Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study. Three clusters showed evidence of reversion of K103N or T215Y/F. 2014 Clinical infectious diseases Abstract HIV K103N;T215F;T215Y 47;56;56 52;63;63 24145878 Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009-2012. Major integrase mutations included T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR, and N155H; multiple accessory mutations were also assessed. 2014 Clinical infectious diseases Abstract HIV E92Q;E92V;F121Y;N155H;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;Y143C;Y143H;Y143R 45;45;52;88;75;75;75;68;37;37;37;59;59;59 50;50;57;93;82;82;82;73;43;43;43;66;66;66 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir. 2013 PloS one Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 148;134;134;134;125;125 153;143;143;143;132;132 IN 16 25 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). 2013 PloS one Abstract HIV M184V 117 122 PI 53 55 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. 2013 PloS one Abstract HIV M184V 61 66 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. 2013 Journal of the American Chemical Society Abstract HIV K103C;K103N;K103Y;Y181C 116;116;116;126 125;125;125;135 RT 159 161 24157905 The impact of HIV-1 reverse transcriptase polymorphisms on responses to first-line nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-1-infected adults. Polymorphisms associated with virologic failure occurred at codons 90 (mostly V90I), 98 (mostly A98S), and 103 (mostly K103R), with adjusted hazard ratios of 1.78 (1.15-2.73; P = 0.009), 1.55 (1.16-2.08; P = 0.003), and 1.75 (1.00-3.05: P = 0.049), respectively. 2013 AIDS (London, England) Abstract HIV A98S;K103R;V90I 96;119;78 100;124;82 24157905 The impact of HIV-1 reverse transcriptase polymorphisms on responses to first-line nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-1-infected adults. Polymorphisms at codon 179, especially V179D/E/T, predicted reduced week 4 responses (P = 0.001) but not virologic failure. 2013 AIDS (London, England) Abstract HIV V179D;V179E;V179T 39;39;39 48;48;48 24157905 The impact of HIV-1 reverse transcriptase polymorphisms on responses to first-line nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-1-infected adults. The mechanisms underlying the slower suppression seen with V179D/E/T deserve further investigation. 2013 AIDS (London, England) Abstract HIV V179D;V179E;V179T 59;59;59 68;68;68 24164431 Short communication: Transmitted HIV drug resistance in antiretroviral-naive pregnant women in north central Nigeria. The specific SDRMs detected were M41L for nucleoside reverse transcriptase inhibitors (NRTIs) and G190A for nonnucleoside reverse transcriptase inhibitors (NNRTIs). 2014 AIDS research and human retroviruses Abstract HIV G190A;M41L 98;33 103;37 NNRTI;NRTI;NNRTI;NRTI 108;42;156;87 143;74;162;92 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Multiple Nef activities can be negated by mutating the SH3 domain binding site (P72Q73V74P75L76R77) to P72A/P75A and this mutation does not affect CD4 downregulation. 2013 Retrovirology Abstract HIV P72A;P75A 103;108 107;112 Nef 9 12 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. To gain insight into the nature of these activities, we constructed the double mutant P72A/P75A. 2013 Retrovirology Abstract HIV P72A;P75A 86;91 90;95 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Unlike LAINeffs described above, the P72A/P75A mutation had a very weak tendency to revert to wild type sequence. 2013 Retrovirology Abstract HIV P72A;P75A 37;42 41;46 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Virus with nef mutated to P72A/P75A closely resembled the wild-type virus in vivo as viral replication and pathogenesis was not significantly altered. 2013 Retrovirology Abstract HIV P72A;P75A 26;31 30;35 Nef 11 14 24172906 Contribution of Gag and protease to variation in susceptibility to protease inhibitors between different strains of subtype B human immunodeficiency virus type 1. Common polymorphisms in protease, including I13V, L63P and A71T, were shown to contribute to this reduction in PI susceptibility, in the absence of major resistance mutations. 2014 The Journal of general virology Abstract HIV A71T;I13V;L63P 59;44;50 63;48;54 PR;PI 24;111 32;113 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The connection subdomain mutations N348I/T369I did not induce any significant structural change; rather, these mutations modulate the conformational dynamics and alter the long-range allosteric communication network between the connection subdomain and NNRTI pocket. 2014 Proteins Abstract HIV N348I;T369I 35;41 40;46 NNRTI 253 258 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. We performed 50-ns molecular dynamics (MD) simulations, followed by essential dynamics, free-energy landscape analyses, and network analyses of RT-DNA, RT-DNA-nevirapine (NVP), and N348I/T369I mutant RT-DNA-NVP complexes. 2014 Proteins Abstract HIV N348I;T369I 181;187 186;192 RT;RT;RT 144;152;200 146;154;202 24188582 Genetic analysis and natural polymorphisms in HIV-1 gp41 isolates from Maputo City, Mozambique. The major polymorphisms in the HR1 were N42S, L54M, A67T, and V72I. 2014 AIDS research and human retroviruses Abstract HIV A67T;L54M;N42S;V72I 52;46;40;62 56;50;44;66 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Although Y135F mutation disrupted the hydrogen bond to HLA-A*2402 His70, newly formed hydrogen bond between T138 and His70 kept the conformation of the epitope in the reconstituted pMHC. 2013 Scientific reports Abstract HIV Y135F 9 14 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. TCR from Y135F- or dually-specific CTL had unique mode of binding to the mutant epitope. 2013 Scientific reports Abstract HIV Y135F 9 14 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Wild type-specific TCR was less fit to F139L mutant suggesting that F139L is an escape from the CTL against the wild type epitope. 2013 Scientific reports Abstract HIV F139L;F139L 39;68 44;73 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Y135F has been reported as a processing mutant but CTL carrying structurally adequate TCR can be found in the patients. 2013 Scientific reports Abstract HIV Y135F 0 5 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Y135F was an early-appearing major mutation, while F139L was a late-appearing mutation which was selected in the patients without Y135F. 2013 Scientific reports Abstract HIV F139L;Y135F;Y135F 51;130;0 56;135;5 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. Here we show that HIV-1 capsid mutants N74D and P90A, which are impaired for interaction with cofactors cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), respectively, cannot replicate in primary human monocyte-derived macrophages because they trigger innate sensors leading to nuclear translocation of NF-kappaB and IRF3, the production of soluble type 1 IFN and induction of an antiviral state. 2013 Nature Abstract HIV N74D;P90A 39;48 43;52 Capsid 24 30 24205814 Impact of resistance mutations on inhibitor binding to HIV-1 integrase. An important hydrogen bond between residues 145 and 148 is present in the wild-type IN but not in the G140S/Q148H mutant, accounting for the structural and dynamical differences of the 140s' loop and ultimately impairing RAL binding in the double mutant. 2013 Journal of chemical information and modeling Abstract HIV G140S;Q148H 102;108 107;113 IN 84 86 24205814 Impact of resistance mutations on inhibitor binding to HIV-1 integrase. However, mutants have emerged, such as E92Q/N155H and G140S/Q148H, which confer resistance to raltegravir (RAL), the first IN strand transfer inhibitor (INSTI) approved by the FDA, and to the recently approved elvitegravir (EVG). 2013 Journal of chemical information and modeling Abstract HIV E92Q;G140S;N155H;Q148H 39;54;44;60 43;59;49;65 INSTI;IN 153;123 158;125 24205814 Impact of resistance mutations on inhibitor binding to HIV-1 integrase. In the simulation of the G140S/Q148H double mutant, we observe spontaneous dissociation of RAL from the active site, followed by an intrahelical swing-back of the 3'-OH group of nucleotide A17, consistent with the experimental observation that the G140S/Q148H mutant exhibits the highest resistance to RAL compared to other IN mutants. 2013 Journal of chemical information and modeling Abstract HIV G140S;G140S;Q148H;Q148H 248;25;31;254 253;30;36;259 IN 324 326 24211331 Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine. However, the K476N mutation partially restored the enzyme's ability to excise 3'-azido-ddGMP on an RNA/DNA, but not on a DNA/DNA, template/primer by selectively decreasing the frequency of secondary RNase H cleavage events. 2014 Antiviral research Abstract HIV K476N 13 18 24211331 Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine. In this study, we have defined the molecular mechanisms of 3'-azido-ddG resistance by performing in-depth biochemical analyses of HIV-1 RT containing mutations L74V, F77L, V106I, L214F, R277K, and K476N (SGS3). 2014 Antiviral research Abstract HIV F77L;K476N;L214F;L74V;R277K;V106I 166;197;179;160;186;172 170;202;184;164;191;177 RT 136 138 24211331 Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine. Pre-steady-state kinetic experiments revealed that the L74V mutation allows RT to effectively discriminate between the natural nucleotide (dGTP) and 3'-azido-ddG-triphosphate (3'-azido-ddGTP). 2014 Antiviral research Abstract HIV L74V 55 59 RT 76 78 24211331 Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine. The L74V mutation was found to severely impair RT's ability to excise the chain-terminating 3'-azido-ddG-monophosphate (3'-azido-ddGMP) moiety. 2014 Antiviral research Abstract HIV L74V 4 8 RT 47 49 24211331 Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine. We also analyzed two additional constructs that either lacked the L74V mutation (SGS3-L74V) or the K476N mutation (SGS3-K476N). 2014 Antiviral research Abstract HIV K476N;L74V 99;66 104;70 24211331 Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine. We reported that 3'-azido-2',3'-dideoxyguanosine (3'-azido-ddG) selected for the L74V, F77L, and L214F mutations in the polymerase domain and K476N and V518I mutations in the RNase H domain of HIV-1 reverse transcriptase (RT). 2014 Antiviral research Abstract HIV F77L;K476N;L214F;L74V;V518I 87;142;97;81;152 91;147;102;85;157 Pol;RT;RT 120;199;222 130;220;224 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. Of 109 genotypic resistance profiles analyzed, the commonest non nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations (RAM) were: K103N (59; 54%)), Y181C (36; 27%)) and G190A (26; 24%)) while the commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was the M184V (89; 81%). 2013 AIDS research and therapy Abstract HIV G190A;K103N;M184V;Y181C 199;160;298;178 204;165;303;183 NRTI;NRTI;NNRTI;NRTI 65;236;109;280 97;268;114;284 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. Env amino acids D470N and E84K that confer the CD4-independent phenotype also regulated entry through low CCR5 levels and GPR15, indicating a common structural basis. 2013 Retrovirology Abstract HIV D470N;E84K 16;26 21;30 Env 0 3 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. Clinical resistance to rilpivirine (RPV), a novel nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI), is associated an E-to-K mutation at position 138 (E138K) in RT together with an M184I/V mutation that confers resistance against emtricitabine (FTC), a nucleoside RT inhibitor (NRTI) that is given together with RPV in therapy. 2014 Journal of virology Abstract HIV E138K;M184I;M184V 160;190;190 165;197;197 NNRTI;NNRTI;NRTI;RT;RT;RT 50;102;287;87;170;273 85;107;291;89;172;275 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. In this context, we have investigated the role of a N348I connection domain mutation that is prevalent in treatment-experienced patients. 2014 Journal of virology Abstract HIV N348I 52 57 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. N348I also enhanced levels of resistance conferred by E138K against RPV and ETR by 2.2- and 2.3-fold, respectively. 2014 Journal of virology Abstract HIV E138K;N348I 54;0 59;5 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. N348I confers resistance to both the NRTI zidovudine (ZDV) and the NNRTI nevirapine (NVP) and was also found to be associated with M184V and to compensate for deficits associated with the latter mutation. 2014 Journal of virology Abstract HIV M184V;N348I 131;0 136;5 NNRTI;NRTI 67;37 72;41 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. Now, we show that both N348I alone and N348I/M184V can prevent or delay the emergence of E138K under pressure with RPV or a related NNRTI, termed etravirine (ETR). 2014 Journal of virology Abstract HIV E138K;M184V;N348I;N348I 89;45;23;39 94;50;28;44 NNRTI 132 137 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. The presence of the N348I or M184V/N348I mutation decreased the replication capacity of E138K virus, and biochemical assays confirmed that N348I, in a background of E138K, impaired RT catalytic efficiency and RNase H activity. 2014 Journal of virology Abstract HIV E138K;E138K;M184V;N348I;N348I;N348I 88;165;29;35;20;139 93;170;34;40;25;144 RT 181 183 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. These findings help to explain the low viral replication capacity of viruses containing the E138K/N348I mutations and how N348I delayed or prevented the emergence of E138K in patients with M184V-containing viruses. 2014 Journal of virology Abstract HIV E138K;E138K;M184V;N348I;N348I 92;166;189;98;122 97;171;194;103;127 24227862 The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. These two mutations can compensate for each other in regard to fitness deficits conferred by each mutation alone, raising the question of why E138K did not arise spontaneously in the clinic following lamivudine (3TC) use, which also selects for the M184I/V mutations. 2014 Journal of virology Abstract HIV E138K;M184I;M184V 142;249;249 147;256;256 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Consistent with an effect on virus entry, selection for viral resistance led to the emergence of two mutations in the gp120 subunit of the viral envelope (Env) glycoprotein, V120Q and A327P, located in the conserved region 1 (C1) and the base of the V3 loop, respectively. 2013 Retrovirology Abstract HIV A327P;V120Q 184;174 189;179 Env;gp120;Env 145;118;155 153;123;158 24239481 Novel piperidinylamino-diarylpyrimidine derivatives with dual structural conformations as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. A cell-based antiviral screening assay showed that some compounds were active against both wild-type and drug-resistant mutant virus strains (K103N+Y181C RT) of HIV-1 (compound 10b3 with EC50 = 0.047 and 4.6 muM, selectivity index = 2145 and 22, respectively). 2013 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 142;148 147;153 RT 154 156 24252532 [Resistance profile of rilpivirine]. In vitro studies and phase III clinical trials have allowed the identification of 16 mutations associated with resistance to RPV K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L. 2013 Enfermedades infecciosas y microbiologia clinica Abstract HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 138;138;138;138;138;185;178;129;129;195;195;153;160;160;160;171 151;151;151;151;151;190;183;136;136;202;202;158;169;169;169;176 24252532 [Resistance profile of rilpivirine]. RPV is a diarylpyrimidine derivative with potent in vitro activity against multiple HIV-1 variants with resistance mutations to first-generation NNRTI such as K103N. 2013 Enfermedades infecciosas y microbiologia clinica Abstract HIV K103N 159 164 NNRTI 145 150 24252532 [Resistance profile of rilpivirine]. The most common resistance mutation that emerges in this setting is E138K. 2013 Enfermedades infecciosas y microbiologia clinica Abstract HIV E138K 68 73 24252532 [Resistance profile of rilpivirine]. This mutation is usually associated with M184I due to a double compensatory effect of this combination, which confers resistance to RPV, as well as to lamivudine and emtricitabine. 2013 Enfermedades infecciosas y microbiologia clinica Abstract HIV M184I 41 46 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Interestingly, introduction of S40F partially rescued the negative effects on budding of CA NTD mutations EE75,76AA and P99A, which both prevent membrane curvature and therefore block budding at an early stage. 2013 Retrovirology Abstract HIV P99A;S40F 120;31 124;35 Capsid 89 91 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. S40F mutation also resulted in stronger Gag-Alix interaction, as detected by yeast 2-hybrid assay. 2013 Retrovirology Abstract HIV S40F 0 4 Gag 40 43 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40F-mediated release defects were exacerbated when the viral-encoded protease (PR) was inactivated or when L domain-1 function was disrupted or when budding was almost completely obliterated by the disruption of both L domain-1 and -2. 2013 Retrovirology Abstract HIV S40F 4 8 PR;PR 74;84 82;86 24267738 The impact of active site mutations of South African HIV PR on drug resistance: Insight from molecular dynamics simulations, binding free energy and per-residue footprints. Against the V82F/I84V variant, saquinavir, indinavir, and nelfinavir lose remarkable entropic contributions relative to both wild-type and V82A C-SA HIV PRs. 2014 Chemical biology & drug design Abstract HIV I84V;V82A;V82F 17;139;12 21;143;16 PR 153 156 24267738 The impact of active site mutations of South African HIV PR on drug resistance: Insight from molecular dynamics simulations, binding free energy and per-residue footprints. Molecular dynamics simulations and binding free energy calculations were used to provide an understanding of the impact of active site drug-resistant mutations of the South African HIV protease subtype C (C-SA HIV PR), V82A and V82F/I84V on drug resistance. 2014 Chemical biology & drug design Abstract HIV I84V;V82A;V82F 233;219;228 237;223;232 PR;PR 185;214 193;216 24268781 Link between primate lentiviral coreceptor usage and Nef function. Here, we show that CXCR4-tropic SIVsmm strains lost their ability to downmodulate TCR-CD3 by evolving unusual Nef mutations that initially reduced (I132V) and subsequently disrupted (I123L and L146F) interaction with the CD3 zeta chain. 2013 Cell reports Abstract HIV I123L;I132V;L146F 183;148;193 189;153;198 Nef 110 113 24275349 Design, synthesis and preliminary SAR studies of novel N-arylmethyl substituted piperidine-linked aniline derivatives as potent HIV-1 NNRTIs. Besides, it is worth noting that compound 7a1 retained moderate inhibitory activity (EC50=4.8 +- 0.95 muM) against the HIV-1 double RT mutant strain (K103N/Y181C). 2014 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 150;156 155;161 RT 132 134 24284781 Sensitive testing of plasma HIV-1 RNA and Sanger sequencing of cellular HIV-1 DNA for the detection of drug resistance prior to starting first-line antiretroviral therapy with etravirine or efavirenz. Conversely, 11/79 (13.9%) patients randomized to etravirine had one polymorphic RAM from the etravirine score in baseline plasma (V90I, V106I or E138A), without any impact on virological outcomes. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138A;V106I;V90I 145;136;130 150;141;134 24300552 Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor and nonprogressor individuals alter Vpr-associated functions. Most notably, the polymorphism of Vpr at R36W and L68M associated with RP shows higher levels of oligomerization, and increased virus replication, whereas R77Q exhibits poor replication kinetics. 2014 The Journal of general virology Abstract HIV L68M;R36W;R77Q 50;41;155 54;45;159 Vpr 34 37 24303887 Major groove binding track residues of the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase enhance cDNA synthesis at high temperatures. An engineered HIV-1O K358R/A359G/S360A RT showed increased cDNA synthesis efficiency above 68C, as determined by qualitative and quantitative reverse transcription polymerase chain reactions. 2013 Biochemistry Abstract HIV A359G;K358R;S360A 27;21;33 32;26;38 RT;Pol;RT 142;164;39 163;174;41 24303887 Major groove binding track residues of the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase enhance cDNA synthesis at high temperatures. Mutations that increased the accuracy of HIV-1M/B RTs were tested in combination with the K358R/A359G/S360A triple mutation. 2013 Biochemistry Abstract HIV A359G;K358R;S360A 96;90;102 101;95;107 RT 50 53 24303887 Major groove binding track residues of the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase enhance cDNA synthesis at high temperatures. Some of them (e.g., F61A, K65R, K65R/V75I, and V148I) had a negative effect on reverse transcription efficiency above 65C. 2013 Biochemistry Abstract HIV F61A;K65R;K65R;V148I;V75I 20;26;32;47;37 24;30;36;52;41 RT 79 100 24303887 Major groove binding track residues of the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase enhance cDNA synthesis at high temperatures. Two of the most thermostable RTs (i.e., mutants T69SSG/K358R/A359G/S360A and K358R/A359G/S360A/E478Q) showed moderately increased fidelity in forward mutation assays. 2013 Biochemistry Abstract HIV A359G;A359G;E478Q;K358R;K358R;S360A;S360A;T69G;T69S 83;61;95;55;77;67;89;48;48 88;66;100;60;82;72;94;54;54 RT 29 32 24318486 Drug resistance mutations and genetic diversity in adults treated for HIV type 1 infection in Mauritania. Overall, the most common DRMs detected were M184V/I (n = 32; 49.2%), K103N (n = 28; 43%), and Y181C (n = 13; 20%). 2014 Journal of medical virology Abstract HIV K103N;M184I;M184V;Y181C 69;44;44;94 74;51;51;99 24318486 Drug resistance mutations and genetic diversity in adults treated for HIV type 1 infection in Mauritania. Thymidine Analog Mutations (TAMs) were found in 26.0% (n = 17) of strains and the most common was T215Y (n = 11, 16.9%). 2014 Journal of medical virology Abstract HIV T215Y 98 103 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. CONCLUSIONS: Resveratrol inhibits HIV-1 strains carrying the M184V mutation in reverse transcriptase. 2014 AIDS (London, England) Abstract HIV M184V 61 66 RT 79 100 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. DESIGN AND METHODS: Evaluation of the activity of resveratrol on infection of primary peripheral blood lymphocytes by wild-type and M184V mutant HIV-1. 2014 AIDS (London, England) Abstract HIV M184V 132 137 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. OBJECTIVE: The M184V mutation in the HIV-1 reverse transcriptase gene is frequent (>50%) in patients, both in resource-rich and resource-limited countries, conferring high-level resistance (>100-fold) to the cytosine analog reverse transcriptase inhibitors lamivudine and emtricitabine. 2014 AIDS (London, England) Abstract HIV M184V 15 20 RT;RT 43;224 64;245 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. Resveratrol inhibited molecular clones and primary isolates carrying M184V, alone or in combination with other reverse transcriptase mutations (resveratrol EC50 values ranging from 2.5 to 7.7 mumol/l). 2014 AIDS (London, England) Abstract HIV M184V 69 74 RT 111 132 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. The reverse transcriptase enzyme of M184V HIV-1 mutants has reduced processivity, resulting in reduced viral replication, particularly at low deoxynucleotide (dNTP) levels. 2014 AIDS (London, England) Abstract HIV M184V 36 41 RT 4 25 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. We assayed both molecular clones and primary isolates of HIV-1, containing M184V alone and in combination with other reverse transcriptase mutations. 2014 AIDS (London, England) Abstract HIV M184V 75 80 RT 117 138 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. We hypothesized that lowering intracellular dNTPs with resveratrol, a dietary supplement, could interfere with replication of M184V HIV-1 mutants. 2014 AIDS (London, England) Abstract HIV M184V 126 131 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. We propose resveratrol as a potential adjuvant in HIV-1 therapy, particularly in resource-limited settings, to help control emtricitabine-resistant M184V HIV-1 mutants. 2014 AIDS (London, England) Abstract HIV M184V 148 153 24328535 Detection of drug resistance-associated mutations in human immunodeficiency virus type 1 integrase derived from drug-naive individuals in Surabaya, Indonesia. In addition, V201I was conserved among all samples. 2014 AIDS research and human retroviruses Abstract HIV V201I 13 18 24328535 Detection of drug resistance-associated mutations in human immunodeficiency virus type 1 integrase derived from drug-naive individuals in Surabaya, Indonesia. Sequencing analysis revealed that no primary mutations associated with drug resistance to integrase inhibitors were detected; however, secondary mutations, V72I, L74I/M, V165I, V201I, I203M, and S230N, were detected in more than 5% of samples. 2014 AIDS research and human retroviruses Abstract HIV I203M;L74I;L74M;S230N;V165I;V201I;V72I 184;162;162;195;170;177;156 189;168;168;200;175;182;160 IN 90 99 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Escape mutations in CTL epitopes restricted by these HLA alleles come at a fitness cost and particularly the T242N mutation in the TW10 CTL epitope in Gag has been demonstrated to decrease the viral replication capacity. 2013 PloS one Abstract HIV T242N 109 114 Gag 151 154 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. In sequences from HLA-B*57/58:01 progressors, 5 additional mutations in Gag were observed: S126N, L215T, H219Q, M228I and N252H. 2013 PloS one Abstract HIV H219Q;L215T;M228I;N252H;S126N 105;98;112;122;91 110;103;117;127;96 Gag 72 75 24346670 Coexistence of HIV-1 variants with dipeptidic insertion in the reverse transcriptase gene. After confirmation of treatment failure, resistance to antiretroviral drugs testing was performed and two variants with the insertions of the aminoacids Ser-Gly/Ser-Ala at codon 69 of reverse transcriptase were detected, besides the T69S mutation. 2013 Revista de saude publica Abstract HIV T69S 233 237 RT 184 205 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In this study, three coevolved protease-substrate complexes (AP2VNC-p1V82A, LP1'Fp1-p6D30N/N88D, and SP3'Np1-p6D30N/N88D) were investigated for structural and dynamic properties by molecular modeling and dynamics simulations. 2012 Journal of chemical theory and computation Abstract HIV D30N;D30N;V82A;N88D;N88D 86;111;70;91;116 90;115;74;95;120 PR;Gag;Gag 31;84;109 39;86;111 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Additionally, AS-PCR assays identified 15 additional cases with M46I, five with M46L and four cases with L90M in the protease region. 2013 PloS one Abstract HIV L90M;M46I;M46L 105;64;80 109;68;84 PR 117 125 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Bulk sequencing detected 8 cases with NRTI resistance mutations (one with A62V, one D67E, one T215D, one T215E, two with T215L and two T215S) and 15 with PI resistance mutations (one with N88D and 14 with M46I). 2013 PloS one Abstract HIV A62V;D67E;M46I;N88D;T215D;T215E;T215L;T215S 74;84;205;188;94;105;121;135 78;88;209;192;99;110;126;140 NRTI;PI 38;154 42;156 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Results obtained by AS-PCR and bulk sequencing demonstrated good concordance but the AS-PCR enabled the detection of seven additional drug-resistant cases (one M41L, two with K65R, two with K70R, and one M184V) in the RT region. 2013 PloS one Abstract HIV K65R;K70R;M184V;M41L 175;190;204;160 179;194;209;164 RT 218 220 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. To detect minority populations with drug resistance, we used AS-PCR with mutation-specific primers designed for seven reverse transcriptase inhibitor resistance mutations, M41L, K65R, K70R, K103N, Y181C, M184V, and T215F/Y, and for three protease inhibitor resistance mutations, M46I/L and L90M. 2013 PloS one Abstract HIV K103N;K65R;K70R;L90M;M184V;M41L;M46I;M46L;T215F;T215Y;Y181C 190;178;184;290;204;172;279;279;215;215;197 195;182;188;294;209;176;285;285;222;222;202 RT;PR 118;238 139;246 24359837 HIV-1-infected patients with advanced disease failing a raltegravir-containing salvage regimen in Sao Paulo, Brazil. At failure, major RAL resistance mutations included Q148H/R/K (21/47; 45%), N155H (14/47; 30%), Y143R/H/C (3/47; 6%) and E92Q (1/47; 2%). 2014 International journal of antimicrobial agents Abstract HIV E92Q;N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 121;76;52;52;52;96;96;96 125;81;61;61;61;105;105;105 24359837 HIV-1-infected patients with advanced disease failing a raltegravir-containing salvage regimen in Sao Paulo, Brazil. Most samples with Q148H/R/K also showed G140S/A/C (21/47; 45%). 2014 International journal of antimicrobial agents Abstract HIV G140A;G140C;G140S;Q148H;Q148K;Q148R 40;40;40;18;18;18 49;49;49;27;27;27 24379202 In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Furthermore, E138K, Y181C, and K101E mutant viruses that are associated with ETR and RPV were susceptible to MK-1439 with a fold change (FC) of <3. 2014 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E;Y181C 13;31;20 18;36;25 24379202 In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. In the presence of 50% normal human serum (NHS), MK-1439 showed excellent potency in suppressing the replication of WT virus, with a 95% effective concentration (EC95) of 20 nM, as well as K103N, Y181C, and K103N/Y181C mutant viruses with EC95 of 43, 27, and 55 nM, respectively. 2014 Antimicrobial agents and chemotherapy Abstract HIV K103N;K103N;Y181C;Y181C 189;207;213;196 194;212;218;201 24379202 In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. MK-1439 is a novel NNRTI with a 50% inhibitory concentration (IC50) of 12, 9.7, and 9.7 nM against the wild type (WT) and K103N and Y181C reverse transcriptase (RT) mutants, respectively, in a biochemical assay. 2014 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 122;132 127;137 RT;NNRTI;RT 138;19;161 159;24;163 24387706 Prevalence of drug resistance in human immunodeficiency virus type 1-infected treatment-naive children in Pune, India. In addition, three study sequences displayed three separate HIV-1 protease minor resistance mutations-L10I, A71T, and T74S. 2014 AIDS research and human retroviruses Abstract HIV A71T;L10I;T74S 108;102;118 112;106;122 PR 66 74 24387706 Prevalence of drug resistance in human immunodeficiency virus type 1-infected treatment-naive children in Pune, India. Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, namely A98G and K103N, were observed in two separate sequences. 2014 AIDS research and human retroviruses Abstract HIV A98G;K103N 72;81 76;86 NNRTI;NNRTI 0;47 35;52 24388952 ADS-J1 inhibits HIV-1 infection and membrane fusion by targeting the highly conserved pocket in the gp41 NHR-trimer. However, ADS-J1 was less effective in binding to N36Fd trimer with mutations in the gp41 pocket region, such as N36(Q64A)Fd, N36(Q64L)Fd, N36(A67G)Fd, N36(A67S)Fd, and N36(Q66R)Fd, as well as less effective in blocking 6-HB formation between C34 and these mutant N36Fd trimers. 2014 Biochimica et biophysica acta Abstract HIV A67G;A67S;Q64A;Q64L;Q66R 142;155;116;129;172 146;159;120;133;176 gp41 84 88 24401644 Differential impact of APOBEC3-driven mutagenesis on HIV evolution in diverse anatomical compartments. G73S in protease; M184I, M230I in reverse transcriptase) and two other patients' rectal tissues (M184I, M230I in reverse transcriptase) while such mutations were absent from paired peripheral blood mononuclear cells. 2014 AIDS (London, England) Abstract HIV M184I;M184I;M230I;M230I;G73S 18;97;25;104;0 23;102;30;109;4 RT;RT;PR 34;113;8 55;134;16 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. In spreading infection, NL4-3 with Vif E88A/W89A mutation replicated comparably to wild-type virus in permissive CEM-SS cells, but not in multiple APOBEC3 expressing non-permissive CEM cells. 2014 Virology Abstract HIV E88A;W89A 39;44 43;48 Vif 35 38 24419343 Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine. The E138A substitution, typically associated with decreased virologic responses to ETV- and RPV-containing regimens, confers a clear fitness advantage to the virus in the presence of FTC and decreases FTC susceptibility 4.7-fold. 2014 Antimicrobial agents and chemotherapy Abstract HIV E138A 4 9 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Surprisingly, the replacement of His108 to alanine also contributed to the Vif structure. 2014 Retrovirology Abstract HIV H108A 33 50 Vif 75 78 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. Mutation K103N conferring resistance to non nucleoside reverse transcriptase inhibitors and thymidine analogue mutations (M41L, L210W) were found only in one adult and child patient, respectively. 2014 BMC infectious diseases Abstract HIV K103N;L210W;M41L 9;128;122 14;133;126 NRTI 44 76 24423716 Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India. The most frequent mutations were H69K and I93L (52 of 52 strains), followed by I15V (80.7%), L19I (69.2%), M36I (67.3%), R41K (94.2%), L63P (61.5%), and L89M (82.7%). 2014 Journal of infection in developing countries Abstract HIV H69K;I15V;I93L;L19I;L63P;L89M;M36I;R41K 33;79;42;93;135;153;107;121 37;83;46;97;139;157;111;125 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. CONCLUSIONS: Since the combination of the R263K mutation and the M50I polymorphism results in a virus with decreased viral fitness and limited cross-resistance, the R263K resistance pathway may represent an evolutionary dead-end. 2014 Retrovirology Abstract HIV M50I;R263K;R263K 65;42;165 69;47;170 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. However, the emergence of the resistance mutation R263K followed by the polymorphic substitution M50I has been observed in cell culture. 2014 Retrovirology Abstract HIV M50I;R263K 97;50 101;55 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. RESULTS: Using biochemical cell-free strand-transfer assays and resistance assays in TZM-bl cells, we demonstrate that the M50I polymorphism in combination with R263K increases resistance to DTG in tissue culture and in biochemical assays but does not restore the viral fitness cost associated with the R263K mutation. 2014 Retrovirology Abstract HIV M50I;R263K;R263K 123;161;303 127;166;308 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The M50I polymorphism is also observed in 10-25% of INSTI-naive patients and has been reported in combination with R263K in a patient failing treatment with RAL. 2014 Retrovirology Abstract HIV M50I;R263K 4;115 8;120 INSTI 52 57 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. Non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs were present in all (100%) children whose viruses harboured DRMs: K103N in 43%; Y181C, K101E and V106M each in 29%; and Y188L in 14%. 2014 Journal of the International AIDS Society Abstract HIV K101E;K103N;V106M;Y181C;Y188L 147;126;157;140;180 152;131;162;145;185 NNRTI;NNRTI 0;48 36;53 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. The D67N thymidine-analogue mutation was observed in only two children whose mothers had received chemoprophylaxis of mother-to-child transmission (MTCT). 2014 Journal of the International AIDS Society Abstract HIV D67N 4 8 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. M184V and K103N were the most common mutations amongst children on NNRTI-based and M184V among children on PI-based regimens. 2014 AIDS research and therapy Abstract HIV K103N;M184V;M184V 10;83;0 15;88;5 NNRTI;PI 67;107 72;109 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. The most prevalent ADR mutations were the M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). 2014 AIDS research and therapy Abstract HIV K103N;K103S;M184V;Y181C;Y181I;Y181V;Y181Y 58;58;42;79;79;79;79 65;65;47;90;90;90;90 24463394 Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. DESIGN AND METHODS: We tested the ability of DTG-resistant viruses containing either the R263K or G118R and/or H51Y mutations to develop further resistance against several reverse transcriptase inhibitors during in-vitro selection experiments. 2014 AIDS (London, England) Abstract HIV G118R;H51Y;R263K 98;111;89 103;115;94 RT 172 193 24463394 Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. Now, we sought to investigate the facility with which resistance on the part of R263K-containing viruses might develop. 2014 AIDS (London, England) Abstract HIV R263K 80 85 24463394 Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. The R263K integrase resistance mutation was observed in two of these individuals who received suboptimal background regimens. 2014 AIDS (London, England) Abstract HIV R263K 4 9 IN 10 19 24463394 Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. We have previously selected mutations at position R263K, G118R, H51Y, and E138K as being associated with low-level resistance to DTG. 2014 AIDS (London, England) Abstract HIV E138K;G118R;H51Y;R263K 74;57;64;50 79;62;68;55 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Importantly, some of these new inhibitors retain greater antiviral efficacy compared to that of RAL when tested against a panel of IN mutants that included Y143R, N155H, G140S/Q148H, G118R, and E138K/Q148K. 2014 Journal of medicinal chemistry Abstract HIV E138K;G118R;G140S;N155H;Q148H;Q148K;Y143R 194;183;170;163;176;200;156 199;188;175;168;181;205;161 IN 131 133 24473489 Incidence of transmitted antiretroviral drug resistance in treatment-naive HIV-1-infected persons in a large South Central United States clinic. The K103N/S and E138A reverse transcriptase mutations were the most common DRMs identified, both present in 3.5% of patients. 2014 The Annals of pharmacotherapy Abstract HIV E138A;K103N;K103S 16;4;4 21;11;11 RT 22 43 24473489 Incidence of transmitted antiretroviral drug resistance in treatment-naive HIV-1-infected persons in a large South Central United States clinic. The L90M mutation was the most frequently observed PI SDRM (1.6%), while the T215C/D/I mutation was the most common NRTI SDRM identified (1.9%). 2014 The Annals of pharmacotherapy Abstract HIV L90M;T215C;T215D;T215I 4;77;77;77 8;86;86;86 NRTI;PI 116;51 120;53 24478426 Reversible and efficient activation of HIV-1 cell entry by a tyrosine-sulfated peptide dissects endocytic entry and inhibitor mechanisms. Surprisingly, both independent adaptations included gp120 mutations S298N, F313L, and N403S, supporting other evidence that they function by weakening gp120's grip on gp41 rather than by altering gp120 binding to specific CCR5 sites. 2014 Journal of virology Abstract HIV F313L;N403S;S298N 75;86;68 80;91;73 gp120;gp120;gp120;gp41 52;151;196;167 57;156;201;171 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Transduction of certain cell types increases significantly when CypA binding to particular HIV-1 CA mutants, i.e., A92E, is prevented. 2014 Retrovirology Abstract HIV A92E 115 119 Capsid 97 99 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The G196R substitution in RT was detected from 6 of 7 animals at week 4 post-infection and remained in virus from 4 of 6 animals at week 30. 2014 PloS one Abstract HIV G196R 4 9 RT 26 28 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Virus from four high virus load animals showed several common mutations within RT, including L74V or V75L, G196R, L214F, and K275R. 2014 PloS one Abstract HIV G196R;K275R;L214F;L74V;V75L 107;125;114;93;101 112;130;119;97;105 RT 79 81 24498124 New insights into the in silico prediction of HIV protease resistance to nelfinavir. In the present study, we used bioinformatics tools to evaluate the impact of the unusual mutations D30V and V32E over the dynamics of the PR-Nelfinavir complex, considering that codons involved in these mutations were previously related to major drug resistance to Nelfinavir. 2014 PloS one Abstract HIV D30V;V32E 99;108 103;112 PR 138 140 24498124 New insights into the in silico prediction of HIV protease resistance to nelfinavir. The D30V mutation triggered a subtle change in the PR structure, which was also observed for the well-known Nelfinavir resistance mutation D30N, while the V32E exchange presented a much more dramatic impact over the PR flap dynamics. 2014 PloS one Abstract HIV D30N;D30V;V32E 139;4;155 143;8;159 PR;PR 51;216 53;218 24506727 [Molecular characterization of complex recombinant HIV-1 CRF06_cpx subtype detected in Turkey]. While L10I + L33F mutation associated with protease inhibitor (PI) resistance was detected in both of the patients, K219N mutation associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance was detected only in the male patient. 2014 Mikrobiyoloji bulteni Abstract HIV K219N;L10I;L33F 116;6;13 121;10;17 NRTI;PR;NRTI;PI 147;43;191;63 179;51;195;65 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Consistent with roles for Arg231 and Lys258 in sequence specific and non-specific binding, respectively, the R231E mutation altered integration site nucleotide preferences while K258E had no effect. 2014 Nucleic acids research Abstract HIV K258E;R231E 178;109 183;114 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. S119A and S119T integrase mutations significantly altered base preferences at positions -3 and 7 from the site of viral DNA joining. 2014 Nucleic acids research Abstract HIV S119T;S119A 10;0 15;5 IN 16 25 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The S119A preference moreover mimicked wild-type PFV selectivity at these positions. 2014 Nucleic acids research Abstract HIV S119A 4 9 24520823 Human protein Staufen-2 promotes HIV-1 proliferation by positively regulating RNA export activity of viral protein Rev. hStau-2 mutant, with mutations at Q314R-A318F-K319E, deficient of binding Rev, failed to promote hStau-2 dependent Rev activity and viral production, validating the essentiality of this protein-protein interaction. 2014 Retrovirology Abstract HIV A318F;K319E;Q314R 40;46;34 45;51;39 Rev;Rev 74;115 77;118 24522307 [Patterns of HIV-1 resistance to antiretroviral drugs in patients with virologic failure: Roosevelt Hospital, Guatemala 2008-2012]. Most frequent mutations were: M184V, K103N and K65R (71, 50 and 22%, respectively). 2013 Revista chilena de infectologia Abstract HIV K103N;K65R;M184V 37;47;30 42;51;35 24574397 Activities of transmitted/founder and chronic clade B HIV-1 Vpu and a C-terminal polymorphism specifically affecting virion release. Conversely, the virion release function of impaired primary clones was restored by creating a G76W substitution. 2014 Journal of virology Abstract HIV G76W 94 98 24574397 Activities of transmitted/founder and chronic clade B HIV-1 Vpu and a C-terminal polymorphism specifically affecting virion release. Primary Vpu clones encoding a W76G polymorphism, or site-directed mutants encoding a W76G substitution, were impaired in their ability to enhance virion release, but they were not defective for BST2 surface downregulation. 2014 Journal of virology Abstract HIV W76G;W76G 30;85 34;89 Vpu 8 11 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. The most prevalent nucleoside reverse transcriptase inhibitor resistance mutations were M184I/V (90%), Q151M (24%), and S215F/Y (24%). 2014 AIDS (London, England) Abstract HIV M184I;M184V;Q151M;S215F;S215Y 88;88;103;120;120 95;95;108;127;127 NRTI 19 51 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. The most prevalent protease inhibitor resistance mutations were V47A (60%) and I54M (30%). 2014 AIDS (London, England) Abstract HIV I54M;V47A 79;64 83;68 PR 19 27 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. HIV-1, but not N74D capsid-mutant HIV-1, was markedly sensitive to TNPO3 depletion, but they infected 1-1340 segment-complemented Nup358 knockout cells equivalently. 2014 PLoS pathogens Abstract HIV N74D 15 19 Capsid 20 26 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Human and mouse CypA both rescued HIV-1 in CypA gene-/- Jurkat cells and TRIM-Nup358Cyp fusions derived from each species were equally antiviral; each also inhibited both WT and N74D virus. 2014 PLoS pathogens Abstract HIV N74D 178 182 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Polymorphism mutation sites with mutation rates in the protease region higher than 60.0% were: L63A/P/S/T 89.7%, V77I 82.2%, I72E/M/K/T/V 80.4%, I93L 75.7%, and E35D 72.9%. 2014 PloS one Abstract HIV E35D;I72E;I72K;I72M;I72T;I72V;I93L;L63A;L63P;L63S;L63T;V77I 161;125;125;125;125;125;145;95;95;95;95;113 165;137;137;137;137;137;149;105;105;105;105;117 PR 55 63 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Polymorphism mutation sites with mutation rates in the RT region higher than 60.0% were: I135A/L/M/R/T/V 93.5%, T200A/E/I/P/V 89.7%, Q278E/K/N/T 88.8%, S162C/Y 82.2%, and K277R/S 66.4%. 2014 PloS one Abstract HIV I135A;I135L;I135M;I135R;I135T;I135V;K277R;K277S;Q278E;Q278K;Q278N;Q278T;S162C;S162Y;T200A;T200E;T200I;T200P;T200V 89;89;89;89;89;89;171;171;133;133;133;133;152;152;112;112;112;112;112 104;104;104;104;104;104;178;178;144;144;144;144;159;159;125;125;125;125;125 RT 55 57 24589294 Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study. Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. 2014 HIV medicine Abstract HIV Y181C 162 167 NNRTI;NNRTI 83;130 118;135 24603872 Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy. The only raltegravir-resistant MV detected was an E138K mutation in one participant by Illumina sequencing, but not by 454. 2014 PloS one Abstract HIV E138K 50 55 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. In addition, the N42S mutation (12.9%) associated with T-20 hypersusceptibility was detected at a high frequency. 2014 Journal of Korean medical science Abstract HIV N42S 17 21 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. Minor T-20 resistance mutations such as L45M (1.2%), N126K (1.2%), and E137K (6.7%) were detected, but the critical T-20 resistance mutations were not detected in the gp41 HR1 and HR2 regions. 2014 Journal of Korean medical science Abstract HIV E137K;L45M;N126K 71;40;53 76;44;58 gp41 167 171 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. This study of gp41 polymorphisms showed that insertions in the fourth threonine (74.8%) and L7M substitutions (85.3%) were more frequent in the fusion peptide motif in Korean HIV-1 isolates compared with those from other countries. 2014 Journal of Korean medical science Abstract HIV L7M 92 95 gp41 14 18 24628038 A study of the molecular mechanism of binding kinetics and long residence times of human CCR5 receptor small molecule allosteric ligands. The maraviroc time-dependent transition was influenced by F85L, W86A, Y108A, I198A and Y251A mutations of CCR5. 2014 British journal of pharmacology Abstract HIV F85L;I198A;W86A;Y108A;Y251A 58;77;64;70;87 62;82;68;75;92 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Among these mutations, nine exhibited positive selection, three were natural polymorphisms (L63S/V/H) in a codon associated with drug resistance, and six were unusual mutations (L5F, D29V, L63R/G, P79L and T91V). 2014 BMC bioinformatics Abstract HIV D29V;L5F;L63G;L63H;L63R;L63S;L63V;P79L;T91V 183;178;189;92;189;92;92;197;206 187;181;195;100;195;100;100;201;210 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The D29V mutation likely confers a selection advantage in viruses; however, in silico, presence of this mutation results in unstable enzyme/PI complexes, that possibly induce resistance to PIs. 2014 BMC bioinformatics Abstract HIV D29V 4 8 PI;PI 140;189 142;192 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The D29V mutation, with a prevalence of 1.32% in the studied population, was only found in patients treated with antiretroviral drugs. 2014 BMC bioinformatics Abstract HIV D29V 4 8 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Using in silico modelling, we observed that D29V formed unstable protease complexes when were docked with lopinavir, saquinavir, darunavir, tipranavir, indinavir and atazanavir. 2014 BMC bioinformatics Abstract HIV D29V 44 48 PR 65 73 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm. 2014 The Journal of antimicrobial chemotherapy Abstract HIV K65R;Y115F 35;41 39;46 24657622 Raltegravir and elvitegravir-resistance mutation E92Q affects HLA-B*40:02-restricted HIV-1-specific CTL recognition. EL11-specific CTLs recognized E92Q peptide-pulsed and E92Q mutant virus-infected cells less effectively than EL11 peptide-pulsed and wild-type virus-infected cells, respectively. 2014 Microbes and infection Abstract HIV E92Q;E92Q 30;54 34;58 24657622 Raltegravir and elvitegravir-resistance mutation E92Q affects HLA-B*40:02-restricted HIV-1-specific CTL recognition. Ex vivo ELISpot analysis showed no induction of E92Q-specific T cells in chronically HIV-1-infected individuals. 2014 Microbes and infection Abstract HIV E92Q 48 52 HIV infections 85 99 24657622 Raltegravir and elvitegravir-resistance mutation E92Q affects HLA-B*40:02-restricted HIV-1-specific CTL recognition. We here investigated the effect of a raltegravir and elvitegravir-resistance mutation (E92Q) on HLA-B*40:02-restricted Int92-102 (EL11: ETGQETAYFLL)-specific CTLs. 2014 Microbes and infection Abstract HIV E92Q 87 91 24663024 Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. BI 224436 also retains full antiviral activity against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. 2014 Antimicrobial agents and chemotherapy Abstract HIV E92Q;N155S;Q148H 133;115;122 137;120;127 INSTI 84 89 24663024 Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. Passage of virus in the presence of inhibitor selected for either A128T, A128N, or L102F primary resistance substitutions, all mapping to a conserved allosteric pocket on the catalytic core of integrase. 2014 Antimicrobial agents and chemotherapy Abstract HIV A128N;A128T;L102F 73;66;83 78;71;88 IN 193 202 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Depletion of none of the selected candidate genes led to the reversal of CsA-dependent phenotype of the A92E mutant. 2014 PloS one Abstract HIV A92E 104 108 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Our data suggest that none of the 26 genes tested is responsible for the dependence of the A92E mutant on CsA. 2014 PloS one Abstract HIV A92E 91 95 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Resistance to CsA is conferred by A92E or G94D substitutions in CA. 2014 PloS one Abstract HIV A92E;G94D 34;42 38;46 Capsid 64 66 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. However, enzymatic studies carried out with purified RTs revealed that in the presence of M41L/L210W/T215Y, H208Y increases the RT's ability to unblock and extend primers terminated with zidovudine, tenofovir and in a lesser extent, stavudine. 2014 Antiviral research Abstract HIV L210W;M41L;T215Y;H208Y 95;90;101;108 100;94;106;113 RT;RT 53;128 56;130 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. NRTI susceptibility was not affected by the addition of H208Y in phenotypic assays carried out in MT-4 cells using recombinant HIV-1 containing wild-type (subtype B, BH10), H208Y, M41L/L210W/T215Y or M41L/H208Y/L210W/T215Y RTs. 2014 Antiviral research Abstract HIV H208Y;L210W;L210W;M41L;M41L;T215Y;T215Y;H208Y;H208Y 205;185;211;180;200;191;217;56;173 210;190;216;184;204;196;222;61;178 NRTI;RT 0;223 4;226 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. The amino acid substitution H208Y shows increased prevalence in patients treated with nucleoside analogues and is frequently associated with TAM1 mutations. 2014 Antiviral research Abstract HIV H208Y 28 33 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. The increased rescue efficiency of the M41L/H208Y/L210W/T215Y RT was observed in the presence of ATP but not with GTP or ITP. 2014 Antiviral research Abstract HIV H208Y;L210W;M41L;T215Y 44;50;39;56 49;55;43;61 RT 62 64 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. These effects were observed with DNA/DNA complexes (but not with RNA/DNA) and resulted from the higher ATP-dependent excision activity of the M41L/H208Y/L210W/T215Y RT compared with the M41L/L210W/T215Y mutant. 2014 Antiviral research Abstract HIV H208Y;L210W;L210W;M41L;M41L;T215Y;T215Y 147;191;153;142;186;159;197 152;196;158;146;190;164;202 RT 165 167 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. These studies provide a mechanistic explanation for the association of TAM-1 and H208Y mutations in viral isolates from patients treated with NRTIs. 2014 Antiviral research Abstract HIV H208Y 81 86 NRTI 142 147 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. Thymidine analogue resistance mutations (TAMs) in HIV-1 reverse transcriptase (RT) associate in two clusters: (i) TAM1 (M41L, L210W and T215Y) and TAM2 (D67N, K70R, K219E/Q, and sometimes T215F). 2014 Antiviral research Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 153;165;165;159;126;120;188;136 157;172;172;163;131;124;193;141 RT;RT 56;79 77;81 24667336 Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients. We studied the molecular mechanism favoring the selection of H208Y in the presence of zidovudine, tenofovir and other nucleoside RT inhibitors (NRTIs). 2014 Antiviral research Abstract HIV H208Y 61 66 NRTI;RT 144;129 149;131 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Similarly, IG insertion or MG insertion and S11R mutation dramatically diminished or completely abolished viral infectivity in other envelopes of subtype C or CRF07_BC. 2014 PloS one Abstract HIV S11R 44 48 Env 133 142 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. These results suggest that the effects of IG insertion and P16R mutation or MG insertion and S11R mutation on CXCR4 usage are context dependent, and additional mutations elsewhere in the envelope are needed to compensate for these fitness-reducing alterations. 2014 PloS one Abstract HIV P16R;S11R 59;93 63;97 Env 187 195 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Two amino acid insertions between positions 13 and 14, as well as arginine substitution at position 11 or 16 (IG insertion and P16R mutation or MG insertion and S11R mutation), conferred the chimeric viruses CXCR4-tropic features, which were same as subtype C X4 viruses. 2014 PloS one Abstract HIV P16R;S11R 127;161 131;165 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. 2014 PloS one Abstract HIV D232N;V151I 116;106 121;112 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. 2014 PloS one Abstract HIV E92Q;N155H;Q148R;T97A 133;104;111;140 137;109;116;144 24692786 Effectiveness and metabolic complications after 96 weeks of a generic fixed-dose combination of stavudine, lamivudine, and nevirapine among antiretroviral-naive advanced HIV-infected patients in Thailand: A prospective study. Of 13 patients who developed virologic failure, 76.9% and 61.5% had M184V/I and Y181C/I mutations, respectively. 2008 Current therapeutic research, clinical and experimental Abstract HIV M184I;M184V;Y181C;Y181I 68;68;80;80 75;75;87;87 24698843 Comparison of ultra-deep versus Sanger sequencing detection of minority mutations on the HIV-1 drug resistance interpretations after virological failure. Three resistance mutations with more than 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). 2014 AIDS (London, England) Abstract HIV A98S;E138A;V179I 86;98;114 90;103;119 24698843 Comparison of ultra-deep versus Sanger sequencing detection of minority mutations on the HIV-1 drug resistance interpretations after virological failure. Y181C and T215Y were the most frequent mutations associated with interpretation differences. 2014 AIDS (London, England) Abstract HIV T215Y;Y181C 10;0 15;5 24699043 Limited evolution but increasing trends of primary non-nucleoside reverse transcriptase inhibitor resistance mutations in therapy-naive HIV-1-infected individuals in India. Common mutations included T69D and D67N (NRTI mutations), and L100I, K101E, K103N and Y181C (NNRTI mutations). 2014 Antiviral therapy Abstract HIV D67N;K101E;K103N;L100I;T69D;Y181C 35;69;76;62;26;86 39;74;81;67;30;91 NNRTI;NRTI 93;41 98;45 24704709 Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. CONCLUSIONS: Based on 15,991 US clinical samples from HIV-1-infected patients, the frequency of most known rilpivirine RAMs apart from Y181C was low. 2014 Antiviral therapy Abstract HIV Y181C 135 140 HIV infections 54 68 24704709 Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. However, the L100I+K103N combination (without rilpivirine RAMs), at <2% prevalence, was associated with a rilpivirine FC>2.0. 2014 Antiviral therapy Abstract HIV K103N;L100I 19;13 24;18 24704709 Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. Median FC values >2.0 were observed for clinical isolates with rilpivirine RAMs K101P, E138Q/R, Y181C/I/V, Y188L or M230L, and for the combination of E138K with M184I/V, and K101E with M184I. 2014 Antiviral therapy Abstract HIV E138K;E138Q;E138R;K101E;K101P;M184I;M184I;M184V;M230L;Y181C;Y181I;Y181V;Y188L 150;87;87;174;80;161;185;161;116;96;96;96;107 155;94;94;179;85;168;190;168;121;105;105;105;112 24704709 Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. METHODS: In total, 15,991 samples submitted to Monogram Biosciences (South San Francisco, CA, USA) for routine resistance testing between January 2010 and June 2011 were assessed for the presence of known rilpivirine RAMs K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L; non-nucleoside reverse transcriptase inhibitor (NNRTI) RAMs K103N, L100I and L100I+K103N; and the nucleoside reverse transcriptase inhibitor (NRTI) RAMs M184I/V and their combinations with rilpivirine RAMs. 2014 Antiviral therapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;K103N;K103N;L100I;L100I;M184I;M184V;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 231;231;231;231;231;278;271;222;222;357;380;364;374;450;450;288;288;246;253;253;253;264 244;244;244;244;244;283;276;229;229;362;385;369;379;457;457;295;295;251;262;262;262;269 NNRTI;NRTI;NNRTI;NRTI;Capsid 297;395;345;439;90 333;427;350;443;92 24704709 Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. Most rilpivirine FC values >2.0 were associated with etravirine FC values >2.9 for individual rilpivirine RAMs and those combined with M184I/V. 2014 Antiviral therapy Abstract HIV M184I;M184V 135;135 142;142 24704709 Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. The prevalence of most rilpivirine RAMs and combinations of NNRTI RAMs of interest was low (<=3%), except for Y181C (7%). 2014 Antiviral therapy Abstract HIV Y181C 110 115 NNRTI 60 65 24704709 Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine. There was no relationship between the presence of K103N and rilpivirine FC. 2014 Antiviral therapy Abstract HIV K103N 50 55 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. The most frequent mutations were K103N and M184VI. 2014 BMC infectious diseases Abstract HIV K103N;M184I;M184V 33;43;43 38;49;49 24709063 A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo. The rt gene of RT-SHIV/AE lacked the common mutation (T215I) associated with drug resistance. 2014 Microbes and infection Abstract HIV T215I 54 59 RT;RT 4;15 6;17 24710029 New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors. CONCLUSIONS: This study showed that G118R and F121Y mutations, rarely described in patients failing on raltegravir, induced broad cross-resistance to all currently used integrase inhibitors. 2014 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 46;36 51;41 IN 169 178 24710029 New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors. In silico, results showed that G118R and F121Y enzymes were associated with reduced binding affinities to each of the inhibitors and with a decreased number of hydrogen bonds compared with the wild-type complexes. 2014 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 41;31 46;36 24710029 New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors. METHODS: The behaviour of integrases with mutations G118R and F121Y towards raltegravir, elvitegravir and dolutegravir was analysed by evaluating phenotypic susceptibility and by means of in silico techniques (investigating binding affinities and the stabilization of the inhibitors in terms of their hydrogen bond network). 2014 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 62;52 67;57 IN 26 36 24710029 New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors. RESULTS: The phenotypic analysis of G118R and F121Y showed high resistance to raltegravir, elvitegravir and dolutegravir with a fold change >100 when the clinically derived integrase was used, and resistance was also seen when mutations were tested alone in an NL43 backbone, but more often with a lower fold change. 2014 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 46;36 51;41 IN 173 182 24710029 New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors. The aim of this study was to explore, in the same way, the behaviour of dolutegravir in comparison with raltegravir and elvitegravir against the atypical resistance integrase profiles, G118R and F121Y, described in HIV-1 patients failing on raltegravir therapy. 2014 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 195;185 200;190 IN 165 174 24719428 HIV-1 protease-substrate coevolution in nelfinavir resistance. Alterations of residue 30's interaction with the substrate are compensated by the coevolving L449F and S451N cleavage site mutations. 2014 Journal of virology Abstract HIV L449F;S451N 93;103 98;108 24719428 HIV-1 protease-substrate coevolution in nelfinavir resistance. In this study, we investigated the structural basis of coevolution at the Gag p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations. 2014 Journal of virology Abstract HIV D30N;N88D 135;140 139;144 PR;Gag;Gag 145;74;81 153;77;83 24719428 HIV-1 protease-substrate coevolution in nelfinavir resistance. In this study, we investigated the structural basis of coevolution of the p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations by determining crystal structures of wild-type and NFV-resistant HIV-1 protease in complex with p1-p6 substrate peptide variants with L449F and/or S451N. 2014 Journal of virology Abstract HIV D30N;L449F;N88D;S451N 131;294;136;307 135;299;140;312 PR;PR;Gag;Gag 141;231;77;259 149;239;79;261 24729604 HIV-1 drug mutations in children from northern Tanzania. The most frequent mutations were Y181C (n = 8) and K103N (n = 4), conferring resistance to non-nucleoside reverse transcriptase inhibitors. 2014 The Journal of antimicrobial chemotherapy Abstract HIV K103N;Y181C 51;33 56;38 NNRTI 91 127 24738660 Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation acquired during prior nonnucleoside reverse transcriptase inhibitor therapy. CONCLUSIONS: This pilot study demonstrates the successful switch of HIV-1-infected patients who acquired an isolated K103N mutation during previous NNRTI therapy to rilpivirine/tenofovir/emtricitabine. 2014 HIV medicine Abstract HIV K103N 117 122 NNRTI 148 153 HIV infections 68 82 24738660 Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation acquired during prior nonnucleoside reverse transcriptase inhibitor therapy. METHODS: A prospective study was carried out in HIV-1-infected adults who acquired the K103N mutation on failing NNRTI regimens. 2014 HIV medicine Abstract HIV K103N 87 92 NNRTI 113 118 HIV infections 48 62 24738660 Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation acquired during prior nonnucleoside reverse transcriptase inhibitor therapy. OBJECTIVES: Whether treatment-experienced HIV-1-infected patients with an acquired K103N mutation after failing nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens can be treated with rilpivirine is unknown. 2014 HIV medicine Abstract HIV K103N 83 88 NNRTI;NNRTI 112;159 147;164 HIV infections 42 56 24738660 Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation acquired during prior nonnucleoside reverse transcriptase inhibitor therapy. RESULTS: Of 1550 HIV-1-infected patients at the Erasmus Medical Center Rotterdam, we identified 10 HIV-1-infected patients with an isolated K103N mutation acquired after NNRTI failure. 2014 HIV medicine Abstract HIV K103N 140 145 NNRTI 170 175 HIV infections;HIV infections 17;99 31;113 24738660 Successful switch to rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation acquired during prior nonnucleoside reverse transcriptase inhibitor therapy. The aim of this pilot study was to evaluate the efficacy of rilpivirine/tenofovir/emtricitabine in HIV-1-infected patients with an isolated K103N mutation. 2014 HIV medicine Abstract HIV K103N 140 145 HIV infections 99 113 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. DRV is bound inside the active site cavity; however, the inhibitor is oriented almost perpendicular to its typical position and exhibits only 2 direct hydrogen bond and two water-mediated interactions with atoms of PRP51-D25N compared with 11 hydrogen bond interactions seen for DRV bound in the typical position in wild-type enzyme. 2014 ACS chemical biology Abstract HIV D25N 221 225 PR 215 217 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. High resolution crystal structures of PRP51 with the active site D25N mutation revealed a ligand-free form and an inhibitor-bound form showing a unique binding site and orientation for DRV. 2014 ACS chemical biology Abstract HIV D25N 65 69 PR 38 40 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. PRP51-D25N dimer bound two DRV molecules and showed larger separation of 8.7 A between the closest atoms of the two flaps compared with 4.4 A for the ligand-free structure of this mutant. 2014 ACS chemical biology Abstract HIV D25N 6 10 PR 0 2 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The PRP51-D25N dimers were in the open conformation with widely separated flaps, as reported for other highly resistant variants. 2014 ACS chemical biology Abstract HIV D25N 10 14 PR 4 6 24740080 Validation of an oligonucleotide ligation assay for quantification of human immunodeficiency virus type 1 drug-resistant mutants by use of massively parallel sequencing. Nonnucleoside reverse transcriptase inhibitor (K103N, V106M, Y181C, and G190A) and lamivudine (M184V) resistance mutations were quantified in blood-derived plasma RNA and cell DNA specimens by OLA and 454 pyrosequencing. 2014 Journal of clinical microbiology Abstract HIV G190A;K103N;M184V;V106M;Y181C 72;47;95;54;61 77;52;100;59;66 NNRTI 0 35 24740443 Antiretroviral drug resistance among antiretroviral-naive and treatment experienced patients infected with HIV in Iran. Among participants receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. 2014 Journal of medical virology Abstract HIV K103N;M184V 159;174 164;179 24740443 Antiretroviral drug resistance among antiretroviral-naive and treatment experienced patients infected with HIV in Iran. Two (6.7%) antiretroviral-naive participants had K103N mutations. 2014 Journal of medical virology Abstract HIV K103N 49 54 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Among those with acute infection at randomization to FTC/TDF, M184V or I mutations that were predominant at seroconversion waned to background levels within 24 weeks after discontinuing drug. 2014 The Journal of infectious diseases Abstract HIV M184V 62 67 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Minor variants with FTC/TDF mutations K65R, K70E, M184V/I were measured using 454 deep sequencing and a novel allele-specific polymerase chain reaction (AS-PCR) diagnostic tolerant to sequence heterogeneity. 2014 The Journal of infectious diseases Abstract HIV K65R;K70E;M184I;M184V 38;44;50;50 42;48;57;57 Pol 126 136 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Two randomized to FTC/TDF had minor variant M184I detected at 0.53% by AS-PCR or 0.75% by deep sequencing, only 1 of which had low but detectable drug levels. 2014 The Journal of infectious diseases Abstract HIV M184I 44 49 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. CONCLUSIONS: I132L and T139K/R are rare but critical mutations associated with NNRTI-resistance for some NNRTIs. 2014 PloS one Abstract HIV I132L;T139K;T139R 13;23;23 18;30;30 NNRTI;NNRTI 79;105 84;111 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. K101Q, H221Y and T139K can enhance K103N/Y181C/G190A-assocated NNRTI-resistance. 2014 PloS one Abstract HIV G190A;K103N;Y181C;H221Y;T139K;K101Q 47;35;41;7;17;0 52;40;46;12;22;5 NNRTI 63 68 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. K103N+T139K and G190A+T139K mutant induce higher resistance (2.0~14.2-fold and 1.5~7.2-fold, respectively) to all four NNRTIs than K103N or G190A alone mutation. 2014 PloS one Abstract HIV G190A;G190A;K103N;T139K;T139K;K103N 16;140;131;6;22;0 21;145;136;11;27;5 NNRTI 119 125 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Result showed that eight polymorphic mutations (W88C, K101Q, I132L, R135L, T139K/R, H221Y and L228R) in RT for treatment-experienced patients were identified, while they, except for R135L, were completely absent in those from treatment-naive patients. 2014 PloS one Abstract HIV H221Y;I132L;K101Q;L228R;R135L;R135L;T139K;T139R;W88C 84;61;54;94;68;182;75;75;48 89;66;59;99;73;187;82;82;52 RT 104 106 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The I132L and T139K/R mutants exhibited high-level resistance to DLV and NVP and moderate resistance to TMC-125 and EFV, while the K101Q and H221Y mutants exhibited an increased resistance to all four NNRTIs tested. 2014 PloS one Abstract HIV H221Y;I132L;K101Q;T139K;T139R 141;4;131;14;14 146;9;136;21;21 NNRTI 201 207 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The W88C, R135L, and L228R may be RTI-induced adaptive mutations. 2014 PloS one Abstract HIV L228R;R135L;W88C 21;10;4 26;15;8 RT 34 37 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Y181C+K101Q mutant showed a 2.5-, 4.4-, and 4.7-fold higher resistance to TMC-125, NVP and EFV, respectively, than Y181C alone mutant, while Y181C+H221Y or K103N+H221Y mutants had significantly higher resistance to all four NNRTIs than Y181C or K103N mutants. 2014 PloS one Abstract HIV H221Y;H221Y;K101Q;K103N;K103N;Y181C;Y181C;Y181C;Y181C 147;162;6;156;245;115;141;236;0 152;167;11;161;250;120;146;241;5 NNRTI 224 230 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Mutations potentially reducing RPV susceptibility were found in 2.5% of sequences, and they included V179D (1.6%) and G190A (0.8%), with equal distribution among non-B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. 2014 Journal of the International AIDS Society Abstract HIV G190A;V179D 118;101 123;106 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. RESULTS: IAS-USA RPV drug resistance mutations were found in 5.3% sequences, with E138A and E138G being the most common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%), with no significant differences in the frequency between subtype B and non-B clades. 2014 Journal of the International AIDS Society Abstract HIV E138A;E138G;K101E;Y181C 82;92;162;179 87;97;167;184 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. RPV-associated mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International AIDS Society-USA (IAS-USA) mutation list and variants potentially affecting RPV susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the in vitro and in vivo data. 2014 Journal of the International AIDS Society Abstract HIV E138A;E138G;E138K;E138Q;E138R;E138S;F227C;F227L;G190A;G190E;G190S;H221Y;K101E;K101H;K101P;K101T;L100I;M230I;M230L;M230V;V179D;V179F;V179G;V179L;V179T;Y181C;Y181I;Y181V;Y188L 78;78;78;78;78;287;125;318;307;307;307;118;69;278;69;278;271;135;135;328;294;294;294;93;294;100;100;100;111 91;91;91;91;91;292;130;323;316;316;316;123;76;285;76;285;276;142;142;333;305;305;305;98;305;109;109;109;116 AIDS 175 179 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. E138A/K/Q in subtype C decreased RPV susceptibility 2.9-, 5.8-, and 5.4-fold, respectively. 2014 Antiviral research Abstract HIV E138A;E138K;E138Q 0;0;0 9;9;9 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In one of the databases (Stanford University), E138K and E138Q were also more common in RTI-experienced subtype C sequences (1.0% and 1.1%, respectively) than in subtype B sequences (0.3% and 0.6%, respectively). 2014 Antiviral research Abstract HIV E138K;E138Q 47;57 52;62 RT 88 91 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Taken together, these data suggest that E138A could impact treatment or prevention strategies that include RPV in geographic areas where subtype C infection is prevalent. 2014 Antiviral research Abstract HIV E138A 40 45 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. We found that the E138A substitution occurs more frequently in subtype C (range: 5.9-7.5%) than B (range: 0-2.3%) sequences from both treatment-naive and -experienced individuals (p<0.01) in 4 independent genotype databases. 2014 Antiviral research Abstract HIV E138A 18 23 24752610 Design, synthesis, and biological evaluation of novel trifluoromethyl indoles as potent HIV-1 NNRTIs with an improved drug resistance profile. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. 2014 Organic & biomolecular chemistry Abstract HIV Y181C 257 262 24760888 Mutations in HIV-1 reverse transcriptase affect the errors made in a single cycle of viral replication. We show here that four mutations (Y115F, M184V, M184I, and Q151M) in the dNTP-binding pocket of RT that had relatively small effects on the overall HIV-1 mutation rate (less than 3-fold compared to the wild type) significantly increased mutations at some specific positions in the lacZalpha reporter gene. 2014 Journal of virology Abstract HIV M184I;M184V;Q151M;Y115F 48;41;59;34 53;46;64;39 RT 96 98 24769348 New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. 2014 European journal of medicinal chemistry Abstract HIV K103N 32 37 24769348 New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. 2014 European journal of medicinal chemistry Abstract HIV L100I;Y181C 60;50 65;55 24769348 New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences. 2014 European journal of medicinal chemistry Abstract HIV K03N 113 117 24769349 Discovery of novel diarylpyrimidines as potent HIV NNRTIs via a structure-guided core-refining approach. Particularly, compound 7a was the most potent inhibitor against HIV-1 wild-type and double RT mutant HIV-1 strain K103N/Y181C, with an EC50 value of 2.5 nM (SI = 13,740) and 0.33 muM (SI = 107), respectively. 2014 European journal of medicinal chemistry Abstract HIV K103N;Y181C 114;120 119;125 RT 91 93 24795449 Impact of maraviroc-resistant and low-CCR5-adapted mutations induced by in vitro passage on sensitivity to anti-envelope neutralizing antibodies. After 14 passages, the MVC-selected variants harboured substitutions around the CCR5 N-terminal-binding site and V3 (V200I, T297I, K305R and M434I). 2014 The Journal of general virology Abstract HIV K305R;M434I;T297I;V200I 131;141;124;117 136;146;129;122 24798614 Short communication: east meets west: a description of HIV-1 drug resistance mutation patterns of patients failing first line therapy in PEPFAR clinics from Uganda and Nigeria. All subjects with resistance had the M184V mutation. 2014 AIDS research and human retroviruses Abstract HIV M184V 37 42 24798614 Short communication: east meets west: a description of HIV-1 drug resistance mutation patterns of patients failing first line therapy in PEPFAR clinics from Uganda and Nigeria. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. 2014 AIDS research and human retroviruses Abstract HIV M184V 93 98 NNRTI;NNRTI 110;157 145;162 2479983 Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Comparative nucleotide sequence analysis of the reverse transcriptase (RT) coding region from five pairs of sensitive and resistant isolates identified three predicted amino acid substitutions common to all the resistant strains (Asp67----Asn, Lys70----Arg, Thr215----Phe or Tyr) plus a fourth in three isolates (Lys219----Gln). 1989 Science (New York, N.Y.) Abstract HIV D67N;K219Q;K70R;T215F 230;313;244;258 242;326;256;271 RT;Asp;RT 48;230;71 69;233;73 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. An N-terminally maleimido variant of this PEGylated PT, denoted AE21, was conjugated to E275C gp120 to produce the AE21-E275C covalent conjugate. 2014 Biochemistry Abstract HIV E275C;E275C 88;120 93;125 gp120 94 99 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. We have applied the enhanced sampling method to the calculation of the activities of seven non-nucleoside inhibitors of HIV-1 reverse transcriptase, and its Tyr181Cys variant, and have shown that a range of binding orientations is possible depending on the nature of the ligand and the presence of mutations at the binding site. 2014 Journal of chemical theory and computation Abstract HIV Y181C 157 166 RT 126 147 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. A number of the mutants, including G84A/SIEW86-89AAAA (84/86-89), E88A/W89A (88/89), G84A, W89A, L106S and I107S in the 84GxSIEW89 and L102ADQLI107 regions, affected Vif function by disrupting CBF-beta binding. 2014 PloS one Abstract HIV E88A;G84A;G84A;I107S;L106S;W89A;W89A 66;35;85;107;97;71;91 70;39;89;112;102;75;95 Vif 166 169 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Notably, G84D and D104A had stronger effects on the Vif-CUL5 interaction than on the Vif-CBF-beta interaction, indicating that they mainly influenced the CUL5 interaction and implying that the interaction of Vif with CUL5 contributes to the binding of Vif to CBF-beta. 2014 PloS one Abstract HIV D104A;G84D 18;9 23;13 Vif;Vif;Vif;Vif 52;85;208;252 55;88;211;255 24815852 Low prevalence of transmitted drug resistance of HIV-1 during 2008-2012 antiretroviral therapy scaling up in Southern Vietnam. The most common TDR was K103N (0.5%) for NNRTI. 2014 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N 24 29 NNRTI 41 46 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The frequency of reduced susceptibility to didanosine was substantial in the abacavir-exposed group (69.1%).This reduced susceptibility was commonly attributed to L74V/I (n = 44) and to a lesser extent K65R (n = 10) mutations. 2014 PloS one Abstract HIV K65R;L74I;L74V 202;163;163 206;169;169 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The presence of the K65R mutation was more common after abacavir pressure (12.3% vs 1.8%). 2014 PloS one Abstract HIV K65R 20 24 24831260 Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). 2015 Antiviral therapy Abstract HIV E92Q;G140S;N155H;Q148H;Q148K;Q148R;S147G;T66I;Y143C;Y143H;Y143R 78;84;120;109;109;109;102;72;91;91;91 82;89;125;118;118;118;107;76;100;100;100 INSTI 55 60 2483618 Characterization of HIV-1 neutralization escape mutants. Polymerase chain reaction (PCR) amplification of complementary DNA derived from viral RNA, cloning and sequencing identified a base pair (bp) change C----G at position 6663 in variant 110.5/1, predicting a change at amino acid 308 Arg----Gly. 1989 AIDS (London, England) Abstract HIV C6663G;R308G 149;227 172;241 Pol 0 10 24838991 Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV-1: analysis from a national drug-resistance database (ARCA). Among Italian patients the susceptibility to RPV is widespread since some severe substitutions (e.g., E138K are rare), whereas issues exist for others (i.e., E138A, Y181C) which are more frequent. 2014 Journal of medical virology Abstract HIV E138A;E138K;Y181C 158;102;165 163;107;170 24838991 Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV-1: analysis from a national drug-resistance database (ARCA). In Italian HIV-positive HAART-naive patients, prevalence of the main RAMs for RPV is low except for E138A (present in 5.1% of subjects). 2014 Journal of medical virology Abstract HIV E138A 100 105 24838991 Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV-1: analysis from a national drug-resistance database (ARCA). Rilpivirine (RPV) is a novel NNRTI with a mutational pattern different from first-generation drugs of the same class: 16 resistance-associated mutations (RAM) are listed, but the combination E138K + M184I seems to be the most important. 2014 Journal of medical virology Abstract HIV E138K;M184I 191;199 196;204 NNRTI 29 34 24838991 Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV-1: analysis from a national drug-resistance database (ARCA). TDF, EFV, and possibly FTC may predispose to the selection for M184I. 2014 Journal of medical virology Abstract HIV M184I 63 68 24838991 Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV-1: analysis from a national drug-resistance database (ARCA). The combination E138K + M184I is absent in both naive and experienced subjects. 2014 Journal of medical virology Abstract HIV E138K;M184I 16;24 21;29 24854905 [Analysis of HIV genotypic drug resistance among pediatric HIV/AIDS cases with virological failure after free antiretroviral therapy in Yunnan province]. The prevalent mutations associated with drug resistance were M184V/I, K103N, T215F/Y, G190A, Y181C and K101E at the frequencies of 52.1% (38/73), 30.1% (22/73), 21.9% (16/73), 20.5% (15/73), 15.1% (11/73) and 12.3% (9/73) respectively. 2014 Zhonghua yi xue za zhi Abstract HIV G190A;K101E;K103N;M184I;M184V;T215F;T215Y;Y181C 86;103;70;61;61;77;77;93 91;108;75;68;68;84;84;98 24855120 High level of HIV-1 resistance in patients failing long-term first-line antiretroviral therapy in Mali. The treatment duration, median number of NRTI and NNRTI mutations and some reverse transcriptase mutations (T215Y/F/N, L210W, L74I, M41L and H221Y) were associated with the VL at virological failure. 2014 The Journal of antimicrobial chemotherapy Abstract HIV H221Y;L210W;L74I;M41L;T215F;T215N;T215Y 141;119;126;132;108;108;108 146;124;130;136;117;117;117 RT;NNRTI;NRTI 75;50;41 96;55;45 24859049 A virus-envelope paired competitive assay to study entry efficiency of human immunodeficiency virus type 1 in vitro. Entry of viruses using the coreceptor CXCR4 was reduced by adding CXCR4-tropic sgp120 (X4-sgp120) SF2 or LAV expressed in the baculovirus system or by adding X4-sgp120 from NL-952 and NL-V3A virus mutants produced in a HeLa-P4 cell culture expression system. 2014 Journal of virological methods Abstract HIV V3A 187 190 24860155 Comparative replication capacity of raltegravir-resistant strains and antiviral activity of the new-generation integrase inhibitor dolutegravir in human primary macrophages and lymphocytes. In all cellular models analysed, dolutegravir showed full efficacy against N155H and Y143C mutants (dolutegravir fold-change resistance ranging from 0.1 to 1.4; raltegravir fold-change resistance ranging from 0.1 to 10.3). 2014 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Y143C 75;85 80;90 24860155 Comparative replication capacity of raltegravir-resistant strains and antiviral activity of the new-generation integrase inhibitor dolutegravir in human primary macrophages and lymphocytes. In C8166 (the only cell model in which replication capacity was sufficient to perform the test) dolutegravir showed full efficacy against mutations N155H + Y143C (dolutegravir fold-change resistance: 0.6) and a slightly lower activity against G140S+Q148H (dolutegravir fold-change resistance: 2.1). 2014 The Journal of antimicrobial chemotherapy Abstract HIV G140S;N155H;Q148H;Y143C 243;148;249;156 248;153;254;161 24860155 Comparative replication capacity of raltegravir-resistant strains and antiviral activity of the new-generation integrase inhibitor dolutegravir in human primary macrophages and lymphocytes. In MDMs and PBMCs, a dramatic decrease in viral replication was observed for the double mutants N155H + Y143C and G140S + Q148H (ranging from 0.1% to 2.5% compared with wild-type). 2014 The Journal of antimicrobial chemotherapy Abstract HIV G140S;N155H;Q148H;Y143C 114;96;122;104 119;101;127;109 24860155 Comparative replication capacity of raltegravir-resistant strains and antiviral activity of the new-generation integrase inhibitor dolutegravir in human primary macrophages and lymphocytes. The following raltegravir resistance mutations were analysed: N155H, Y143C, N155H + Y143C and G140S+Q148H. 2014 The Journal of antimicrobial chemotherapy Abstract HIV G140S;N155H;N155H;Q148H;Y143C;Y143C 94;62;76;100;69;84 99;67;81;105;74;89 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. A W153L substitution in HIV-1 reverse transcriptase (RT) was recently identified by selection with a novel nucleotide-competing RT inhibitor (NcRTI) termed compound A that is a member of the benzo[4,5]furo[3,2,d]pyrimidin-2-one NcRTI family of drugs. 2014 Antimicrobial agents and chemotherapy Abstract HIV W153L 2 7 RT;RT;RT 30;53;128 51;55;130 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. Biochemical assays demonstrated that W153L alone or in combination with K65R, M184I, K101E, K103N, E138K, and Y181C impaired enzyme processivity and polymerization efficiency but did not diminish RNase H activity, providing mechanistic insights into the low replicative fitness associated with these substitutions. 2014 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E;K103N;K65R;M184I;W153L;Y181C 99;85;92;72;78;37;110 104;90;97;76;83;42;115 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. The nucleoside 3TC retained potency against W153L-containing viruses but not when the M184I substitution was also present. 2014 Antimicrobial agents and chemotherapy Abstract HIV M184I;W153L 86;44 91;49 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. To investigate the impact of W153L, alone or in combination with the clinically relevant RT resistance substitutions K65R (change of Lys to Arg at position 65), M184I, K101E, K103N, E138K, and Y181C, on HIV-1 phenotypic susceptibility, viral replication, and RT enzymatic function, we generated recombinant RT enzymes and viruses containing each of these substitutions or various combinations of them. 2014 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E;K103N;K65R;K65R;M184I;W153L;Y181C 182;168;175;117;133;161;29;193 187;173;180;121;158;166;34;198 RT;RT;RT 89;259;307 91;261;309 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. W153L was also able to reverse the effects of the K65R substitution on resistance to TFV, and K65R conferred hypersusceptibility to compound A. 2014 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;W153L 50;94;0 54;98;5 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. We found that W153L-containing viruses were impaired in viral replicative capacity and were hypersusceptible to tenofovir (TFV) while retaining susceptibility to most nonnucleoside RT inhibitors. 2014 Antimicrobial agents and chemotherapy Abstract HIV W153L 14 19 RT 181 183 24867966 Effects of the W153L substitution in HIV reverse transcriptase on viral replication and drug resistance to multiple categories of reverse transcriptase inhibitors. We show that the mechanism of the TFV hypersusceptibility conferred by W153L is mainly due to increased efficiency of TFV-diphosphate incorporation. 2014 Antimicrobial agents and chemotherapy Abstract HIV W153L 71 76 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. Furthermore, KF116 inhibited the HIV-1 IN variant with the A128T substitution, which confers resistance to the majority of quinoline-based ALLINIs. 2014 PLoS pathogens Abstract HIV A128T 59 64 IN 39 41 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. We also explored the antigenic consequences of three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit disulfide bond, the trimer-stabilizing I559P change in gp41ECTO, and proteolytic cleavage at the gp120-gp41ECTO junction. 2014 Retrovirology Abstract HIV I559P 168 173 gp140;gp120;gp41;gp41 85;226;184;232 90;231;188;236 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. BACKGROUND: The aim of this study was to investigate the role of K101Q, Y181C and H221Y emerging in HIV-1 reverse transcriptase with different mutations patterns in phenotypic susceptibility to currently available NNRTIs (nevirapine NVP, efavirenz EFV) and NRTIs (zidovudine AZT, lamivudine 3TC, stavudine d4T) in China. 2014 BMC infectious diseases Abstract HIV H221Y;K101Q;Y181C 82;65;72 87;70;77 RT;NNRTI;NRTI 106;214;257 127;220;262 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Certainly, the double mutation (K101Q/H221Y) also changes the susceptibility of viruses to NRTIs. 2014 BMC infectious diseases Abstract HIV H221Y;K101Q 38;32 43;37 NRTI 91 96 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Remarkably, K101Q/H221Y was hypersusceptible to EFV (FC = 0.04), but was significantly resistant to the three NRTIs. 2014 BMC infectious diseases Abstract HIV H221Y;K101Q 18;12 23;17 NRTI 110 115 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. RESULTS: Triple-mutation K101Q/Y181C/H221Y and double-mutation K101Q/Y181C resulted in significant increase in NVP resistance (1253.9-fold and 986.4-fold), while only K101Q/Y181C/H221Y brought a 5.00-fold significant increase in EFV resistance. 2014 BMC infectious diseases Abstract HIV H221Y;H221Y;K101Q;K101Q;Y181C;Y181C;K101Q;Y181C 37;179;25;167;31;173;63;69 42;184;30;172;36;178;68;74 24886641 Switching and emergence of CTL epitopes in HIV-1 infection. An escape mutation from tyrosine to phenylalanine at the 135th amino acid (Y135F) of the HIV-1 nef gene is frequently observed in patients with HLA-A*24:02, an HLA Class I allele expressed in ~70% of Japanese persons. 2014 Retrovirology Abstract HIV Y135F 75 80 Nef 95 98 24886641 Switching and emergence of CTL epitopes in HIV-1 infection. Critically, the selection of Y135F also launched the expression of Nef126-10, indicating that the latter epitope is created as a result of escape within the former. 2014 Retrovirology Abstract HIV Y135F 29 34 Nef 67 70 24886641 Switching and emergence of CTL epitopes in HIV-1 infection. Moreover, experiments utilizing antigen specific CTL clones to recognize endogenously-expressed peptides with or without Y135F indicated that this mutation disrupted the antigen expression of Nef134-10. 2014 Retrovirology Abstract HIV Y135F 121 126 Nef 192 195 24886641 Switching and emergence of CTL epitopes in HIV-1 infection. The robust targeting of Nef126-10 following transmission (or in vivo selection) of HIV-1 containing Y135F may explain in part the previously reported stable plasma viral loads over time in the Japanese population, despite the high prevalence of both HLA-A*24:02 and Nef-Y135F in circulating HIV-1 sequences. 2014 Retrovirology Abstract HIV Y135F;Y135F 100;270 105;275 Nef;Nef 24;266 27;269 24886641 Switching and emergence of CTL epitopes in HIV-1 infection. Thirty-five of 46 (76%) HLA-A*24:02-positive patients harbored the Y135F mutation in their plasma HIV-1 RNA. 2014 Retrovirology Abstract HIV Y135F 67 72 24889250 Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers drug resistance and partly compensates for replication deficits. Concurrently, the NRTI mutations T69I and V118I and the NNRTI mutations K103N and Y181C were detected for the first time. 2014 Virology Abstract HIV K103N;T69I;V118I;Y181C 72;33;42;82 77;37;47;87 NNRTI;NRTI 56;18 61;22 24889250 Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers drug resistance and partly compensates for replication deficits. The insertion developed within the context of pre-existing NRTI and NNRTI mutations (M41L, L210W, T215Y and N348I). 2014 Virology Abstract HIV L210W;M41L;N348I;T215Y 91;85;108;98 96;89;113;103 NNRTI;NRTI 68;59 73;63 24889250 Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers drug resistance and partly compensates for replication deficits. We investigated the origin and the effect of insertion D67D-THGERDLGPA within HIV-1 RT from a patient failing antiviral therapy. 2014 Virology Abstract HIV D67D 55 59 RT 84 86 24895029 Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS. In particular, (E)-6-(2''-bromo-4''-cyanovinyl-6''-methoxy)phenoxy-N(2) -(4'-cyanophenyl)pyridin-2,3-diamine (8 c) displayed low-nanomolar antiviral potency (3-7 nM) against wild-type and drug-resistant viral strains bearing the E138K or K101E mutations, which are associated with resistance to rilvipirine (1 b). 2014 ChemMedChem Abstract HIV E138K;K101E 229;238 234;243 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. The E314A mutation, as the E314G mutation reported before, also rendered the YU2.6248V3 infectious in CCR5+ cells, while none of other alanine mutants could infect CCR5+ cells. 2014 PloS one Abstract HIV E314A;E314G 4;27 9;32 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. The G306A and S322A mutations significantly reduced the replication capacity of YU2.6248V3 in GPR15+ cells, while all other alanine substitutions at positions 307, 314, 315, 316, 317 and 318 completely abrogated the infectivity of YU2.6248V3 in GPR15+ cells. 2014 PloS one Abstract HIV G306A;S322A 4;14 9;19 24899199 Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. Conversely, RT-E138K and -Y181C mutations improved the fitness of the IN-G140S/Q148H mutant virus in the presence of raltegravir (RAL); the RT-K103N mutation had no effect. 2014 Journal of virology Abstract HIV E138K;G140S;K103N;Q148H;Y181C 15;73;143;79;26 20;78;148;84;31 IN;RT;RT 70;12;140 72;14;142 24899199 Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. However, both the RT-K103N plus IN-G140S/Q148H and the RT-E138K plus IN-G140S/Q148H mutant viruses had significantly greater fold increases in 50% inhibitory concentration (IC50) of EFV than viruses carrying a single NNRTI mutation. 2014 Journal of virology Abstract HIV E138K;G140S;G140S;K103N;Q148H;Q148H 58;72;35;21;41;78 63;77;40;26;46;83 NNRTI;IN;IN;RT;RT 217;32;69;18;55 222;34;71;20;57 24899199 Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. In the presence of efavirenz (EFV), a virus carrying RT-K103N together with IN-G140S and IN-Q148H (here termed IN-G140S/Q148H) mutations was fitter than a virus with a RT-K103N mutation alone. 2014 Journal of virology Abstract HIV G140S;G140S;K103N;K103N;Q148H;Q148H 79;114;56;171;120;92 84;119;61;176;125;97 IN;IN;IN;RT;RT 76;89;111;53;168 78;91;113;55;170 24899199 Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. Likewise, the IN-G140S/Q148H mutations had no effect on EFV or RPV susceptibility. 2014 Journal of virology Abstract HIV G140S;Q148H 17;23 22;28 IN 14 16 24899199 Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. Likewise, the RT-E138K plus IN-G140S/Q148H mutant virus had significantly greater fold increases in RAL IC50 than that of the IN-G140S/Q148H mutant virus. 2014 Journal of virology Abstract HIV E138K;G140S;G140S;Q148H;Q148H 17;31;129;37;135 22;36;134;42;140 IN;IN;RT 28;126;14 30;128;16 24899199 Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. No effect of INSTI resistance mutations on the fitness of RT-Y181C mutant viruses was observed. 2014 Journal of virology Abstract HIV Y181C 61 66 INSTI;RT 13;58 18;60 24899199 Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. Similarly, in the presence of EFV, the RT-E138K plus IN-G140S/Q148H mutant virus was fitter than one with the RT-E138K mutation alone. 2014 Journal of virology Abstract HIV E138K;E138K;G140S;Q148H 42;113;56;62 47;118;61;67 IN;RT;RT 53;39;110 55;41;112 24900529 Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors. Herein, we disclose the optimization of the antiviral activity in a cell-based assay system leading to the discovery of compound 27, which possessed excellent potency against wild-type HIV-1 (EC50 = 0.2 nM) as well as viruses bearing Y181C and K103N resistance mutations in the reverse transcriptase gene. 2012 ACS medicinal chemistry letters Abstract HIV K103N;Y181C 244;234 249;239 RT 278 299 24909578 Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia. Of the 84 women with complete haplotype data for the aforementioned loci of the dhfr and dhps genes, 53 (63%, 95% CI [50-70]) had quintuple mutants (two with an additional mutation in A581G of dhps). 2014 Malaria journal Abstract HIV A581G 184 189 24909578 Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia. The quintuple mutant haplotype (substitutions in N51I, C59R, S108N in dhfr and A437G and K540E in dhps genes), is associated with SP treatment failure in non-pregnant patients with malaria. 2014 Malaria journal Abstract HIV A437G;C59R;K540E;N51I;S108N 79;55;89;49;61 84;59;94;53;66 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. This activity of Vpr depends on its association with TAK1, since the S79A Vpr mutant lost interaction with TAK1 and was unable to activate TAK1. 2014 Retrovirology Abstract HIV S79A 69 73 Vpr;Vpr 17;74 20;77 24912982 Interactions with DCAF1 and DDB1 in the CRL4 E3 ubiquitin ligase are required for Vpr-mediated G2 arrest. HIV-1 Vpr mutants with a L64P or a R90K mutation maintained the ability to associate with DCAF1 but did not appear to be in a complex with DDB1. 2014 Virology journal Abstract HIV L64P;R90K 25;35 29;39 Vpr 6 9 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. CONCLUSIONS: The E138K substitution failed to restore the defect in viral replication capacity that is associated with R263K, confirming previous selection studies that failed to identify compensatory mutation(s) for the latter primary mutation. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138K;R263K 17;119 22;124 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. E138K has been identified as a secondary mutation for dolutegravir in selection studies and has also been observed as a secondary mutation in the clinic for the integrase inhibitors raltegravir and elvitegravir. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138K 0 5 IN 161 170 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. METHODS: We used biochemical cell-free strand-transfer assays and tissue culture assays to characterize the effects of the E138K/R263K combination of mutations on resistance to dolutegravir, integrase enzyme activity and HIV-1 replication capacity. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138K;R263K 123;129 128;134 IN 191 200 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. RESULTS: We show here that the addition of the E138K substitution to R263K increased the resistance of HIV-1 to dolutegravir but failed to restore viral replication capacity, integrase strand-transfer activity and integration within cellular DNA. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138K;R263K 47;69 52;74 IN 175 184 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. The addition of the E138K substitution to R263K was also less detrimental to integrase strand-transfer activity and integration than a different secondary mutation at position H51Y that had also been selected in culture. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138K;H51Y;R263K 20;176;42 25;180;47 IN 77 86 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. This study suggests that the R263K resistance pathway may represent an evolutionary dead end for HIV in treatment-naive individuals who are treated with dolutegravir and will need to be confirmed by the long-term use of dolutegravir in the clinic. 2014 The Journal of antimicrobial chemotherapy Abstract HIV R263K 29 34 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. We also show that the addition of E138K to R263K did not increase the resistance to raltegravir or elvitegravir. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138K;R263K 34;43 39;48 24917583 Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. We have shown that the R263K mutation commonly emerged during tissue culture selection studies with dolutegravir and conferred low levels of resistance to this drug while simultaneously diminishing both HIV replication capacity and integrase enzymatic activity. 2014 The Journal of antimicrobial chemotherapy Abstract HIV R263K 23 28 IN 232 241 24920794 Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. DTG remained fully effective against all site-directed mutants except G118R and R263K. 2014 Journal of virology Abstract HIV G118R;R263K 70;80 75;85 24920794 Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. Each of the G118R, Y143R, Q148R, R263K, and G140S/Q148R mutations, when introduced into SIV, impaired infectiousness and replication fitness compared to wild-type virus. 2014 Journal of virology Abstract HIV G118R;G140S;Q148R;Q148R;R263K;Y143R 12;44;50;26;33;19 17;49;55;31;38;24 24920794 Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. In contrast, Y143R, Q148R, and N155H all yielded low levels of resistance to RAL. 2014 Journal of virology Abstract HIV N155H;Q148R;Y143R 31;20;13 36;25;18 24920794 Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. The combination of G140S/Q148R conferred high-level resistance to both RAL and EVG (>300- and 286-fold, respectively). 2014 Journal of virology Abstract HIV G140S;Q148R 19;25 24;30 24920794 Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors. Using TZM-bl cells, we demonstrated that the Q148R and N155H mutational pathways conferred resistance to EVG (36- and 62-fold, respectively), whereas R263K also displayed moderate resistance to EVG (12-fold). 2014 Journal of virology Abstract HIV N155H;Q148R;R263K 55;45;150 60;50;155 24920800 Stabilizing the native trimer of HIV-1 Env by destabilizing the heterodimeric interface of the gp41 postfusion six-helix bundle. The mutations V570D and I573D stabilize native Env of the HIV-1 JRFL strain and occlude nonneutralizing epitopes to a greater extent than the previously identified I559P mutation that is at the interface of the NHR trimers in the 6-HB. 2014 Journal of virology Abstract HIV I559P;I573D;V570D 164;24;14 169;29;19 Env 47 50 24924164 HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences. Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%. 2014 The Journal of infectious diseases Abstract HIV K65R 37 41 24924164 HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences. In each case, K65R coexisted unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%. 2014 The Journal of infectious diseases Abstract HIV K65R 14 18 24924164 HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences. In one seroconverter, variants with M184V and nonnucleoside RT inhibitor mutations were also identified at first RNA expression. 2014 The Journal of infectious diseases Abstract HIV M184V 36 41 RT 60 62 24924164 HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences. The samples were screened with sensitive polymerase chain reaction assays for the commonly transmitted M41L and K70R mutations and for K65R, which was undetected by bulk sequencing. 2014 The Journal of infectious diseases Abstract HIV K65R;K70R;M41L 135;112;103 139;116;107 Pol 41 51 24931725 An integrated molecular dynamics, principal component analysis and residue interaction network approach reveals the impact of M184V mutation on HIV reverse transcriptase resistance to lamivudine. Amongst those mutations, M184V was found to cause a complete loss of ligand fitness. 2014 Molecular bioSystems Abstract HIV M184V 25 30 24931725 An integrated molecular dynamics, principal component analysis and residue interaction network approach reveals the impact of M184V mutation on HIV reverse transcriptase resistance to lamivudine. In this study, we report the first account of the molecular impact of M184V mutation on HIV RT resistance to 3TC (lamivudine) using an integrated computational approach. 2014 Molecular bioSystems Abstract HIV M184V 70 75 RT 92 94 24931725 An integrated molecular dynamics, principal component analysis and residue interaction network approach reveals the impact of M184V mutation on HIV reverse transcriptase resistance to lamivudine. Results clearly confirmed that M184V mutation leads to steric conflict between 3TC and the beta branched side chain of valine, decreases the ligand (3TC) binding affinity by ~7 kcal mol(-1) when compared to the wild type, changes the overall conformational landscape of the protein and distorts the native enzyme residue-residue interaction network. 2014 Molecular bioSystems Abstract HIV M184V 31 36 24935032 In vitro analysis of the susceptibility of HIV-1 subtype A and CRF01_AE integrases to raltegravir. Enzymatic activities of subtype A and CRF01_AE INs were analysed with regard to typical 3'-end processing (3'-P) and strand transfer (ST) activities both in the presence and absence of RAL and were compared with subtype B IN as well as with the corresponding INs harbouring the N155H resistance mutation. 2014 International journal of antimicrobial agents Abstract HIV N155H 278 283 IN;IN;IN 47;222;259 50;224;262 24935032 In vitro analysis of the susceptibility of HIV-1 subtype A and CRF01_AE integrases to raltegravir. Subtype A and CRF01_AE INs encoded by these consensus sequences as well as the corresponding enzymes harbouring the N155H resistance mutation were expressed and purified. 2014 International journal of antimicrobial agents Abstract HIV N155H 116 121 IN 23 26 24935032 In vitro analysis of the susceptibility of HIV-1 subtype A and CRF01_AE integrases to raltegravir. The three INs harbouring the N155H mutation presented in vitro low but similar resistance levels to RAL. 2014 International journal of antimicrobial agents Abstract HIV N155H 29 34 IN 10 13 24938655 Co-evolution of compensatory mutation K43E with mutation M41L in long-term HIV antiretroviral treatment. CONCLUSION: We determined that a known compensatory mutation, K43E, frequently co-occurs with the drug resistance mutation M41L and may offer a significant advantage in the long-term survival of such drug resistant strains. 2014 Current HIV research Abstract HIV K43E;M41L 62;123 66;127 24938655 Co-evolution of compensatory mutation K43E with mutation M41L in long-term HIV antiretroviral treatment. In this study, we characterized the emergence and depletion dynamics of a compensatory mutation K43E that correlated with primary nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations in Chinese HIV patients on antiretroviral treatment. 2014 Current HIV research Abstract HIV K43E 96 100 NRTI;NRTI 130;174 162;178 24938655 Co-evolution of compensatory mutation K43E with mutation M41L in long-term HIV antiretroviral treatment. SGA sequences were analyzed by Markov Chain Monte Carlo (MCMC) phylogenetic trees with molecular clock to identify and track compensatory mutation K43E correlated with primary DR mutation M41L. 2014 Current HIV research Abstract HIV K43E;M41L 147;188 151;192 24948706 Early selection of resistance-associated mutations in HIV-1 RT C-terminal domains across different subtypes: role of the genetic barrier to resistance. A360V and T369V were selected by RTI treatment in several subtypes. 2014 The Journal of antimicrobial chemotherapy Abstract HIV T369V;A360V 10;0 15;5 RT 33 36 24948706 Early selection of resistance-associated mutations in HIV-1 RT C-terminal domains across different subtypes: role of the genetic barrier to resistance. A371V was common to treatment-naive isolates. 2014 The Journal of antimicrobial chemotherapy Abstract HIV A371V 0 5 24948706 Early selection of resistance-associated mutations in HIV-1 RT C-terminal domains across different subtypes: role of the genetic barrier to resistance. A371V was selected in subtypes B and C, but is a signature in subtype A. 2014 The Journal of antimicrobial chemotherapy Abstract HIV A371V 0 5 24948706 Early selection of resistance-associated mutations in HIV-1 RT C-terminal domains across different subtypes: role of the genetic barrier to resistance. N348I was observed in all subtypes, while T369I was only selected in subtype C. 2014 The Journal of antimicrobial chemotherapy Abstract HIV T369I;N348I 42;0 47;5 24948706 Early selection of resistance-associated mutations in HIV-1 RT C-terminal domains across different subtypes: role of the genetic barrier to resistance. RESULTS: N348I, T369I and A360V were found at low prevalence in treatment-naive isolates of all subtypes. 2014 The Journal of antimicrobial chemotherapy Abstract HIV A360V;N348I;T369I 26;9;16 31;14;21 24952305 Design and synthesis of a new series of modified CH-diarylpyrimidines as drug-resistant HIV non-nucleoside reverse transcriptase inhibitors. Compound 1d also showed a broad-spectrum inhibitory activity, with an IC50 value of 5.33 muM and 5.05 muM against both HIV-1 double-mutated (K103N/Y181C) strain and HIV-2 strain, respectively. 2014 European journal of medicinal chemistry Abstract HIV K103N;Y181C 141;147 146;152 24960249 Prevalence and virologic consequences of transmitted HIV-1 drug resistance in Uganda. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. 2014 AIDS research and human retroviruses Abstract HIV K103N 109 114 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. 2014 PloS one Abstract HIV N260Q;S128N 29;332 34;337 gp120;gp160;gp160;gp160;gp160;gp41 56;35;109;199;286;66 61;40;114;204;291;70 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. 2014 PloS one Abstract HIV S128N 22 27 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N) that could partially restore the infectivity of mutant N260Q gp120 virus. 2014 PloS one Abstract HIV N260Q;S128N 151;89 156;94 gp120;gp120 82;157 87;162 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. 2014 PloS one Abstract HIV N260Q 132 137 gp160;gp160 138;212 143;217 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We show here that gp160 containing the N260Q mutation reaches the Golgi apparatus during biosynthesis. 2014 PloS one Abstract HIV N260Q 39 44 gp160 18 23 24968596 Reverse transcriptase inhibitors drug resistance mutations in drug-naive HIV type 1 positive Kenyans. NNRTI associated resistance mutations were present at amino acid codon sites G98A (2.56%); K103E (1.3%) and L100F (3.57%) prevalences. 2011 East African medical journal Abstract HIV G98A;K103E;L100F 77;91;108 81;96;113 NNRTI 0 5 24969455 [Resistance evolutionary pathway analysis of HIV-1 CRF_07BC reverse transcriptase]. CONCLUSION: HIV-1 CRF_07BC showed distinctive resistance evolutionary pathway, the mutations K103N,Q197K,V179D and Y188L were the major resistance mutations, and different resistance evolutionary pathways were observed between HIV-1 CRF_07BC and B subtype. 2014 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV K103N;K103N;Q197K;V179D;Y188L 93;93;99;105;115 98;100;104;110;120 24969455 [Resistance evolutionary pathway analysis of HIV-1 CRF_07BC reverse transcriptase]. RESULTS: The major resistance mutations for CRF_07BC were identified including K103N, Q197K, V179D and Y188L. 2014 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV K103N;Q197K;V179D;Y188L 79;86;93;103 84;91;98;108 24969455 [Resistance evolutionary pathway analysis of HIV-1 CRF_07BC reverse transcriptase]. While for B subtype, the major resistance mutations include M184V, K103N,Y181C, T69N,G190A, K238T,Y188H and P225H. 2014 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV G190A;K103N;K238T;M184V;P225H;T69N;Y181C;Y188H 85;67;92;60;108;80;73;98 90;74;99;65;113;86;78;103 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. HIV-1 resistance to zidovudine [AZT (azidothymidine)] is associated with selection of the mutations M41L, D67N, K70R, L210W, T215F/Y and K219Q/E in RT (reverse transcriptase). 2014 The Biochemical journal Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 106;137;137;112;118;100;125;125 110;144;144;116;123;104;132;132 RT;RT 152;148 173;150 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. The single point mutant L63P, which is contained in PRE and POST, has decreased dynamics, particularly in the flap region, and also displays a closed-like conformation of inhibitor-bound states. 2014 FEBS letters Abstract HIV L63P 24 28 24988117 Role of 3 lipoprotein lipase variants in triglycerides in children receiving highly active antiretroviral therapy. Hind III (H+/H-), Pvu II (P+/P-) and S447X (S/X) were determined by polymerase chain reaction and restricted fragment length polymorphism. 2015 The Pediatric infectious disease journal Abstract HIV S447X 37 42 Pol 68 78 24988117 Role of 3 lipoprotein lipase variants in triglycerides in children receiving highly active antiretroviral therapy. Hind III and S447X were not associated with TG at the selected time points. 2015 The Pediatric infectious disease journal Abstract HIV S447X 13 18 24988117 Role of 3 lipoprotein lipase variants in triglycerides in children receiving highly active antiretroviral therapy. Our aim was to evaluate the influence of 3 polymorphisms: Hind III, Pvu II and S447X in plasma TG levels in human immunodeficiency virus-1-infected children under highly active antiretroviral therapy (HAART). 2015 The Pediatric infectious disease journal Abstract HIV S447X 79 84 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. In the protease gene, three subjects (7%) had M46I/L mutations. 2014 PloS one Abstract HIV M46I;M46L 46;46 52;52 PR 7 15 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. Primary HIV-1 drug resistance mutations to RT inhibitors were identified in three (7%) subjects (K65R plus Y181C; N60D; and V106M). 2014 PloS one Abstract HIV K65R;N60D;V106M;Y181C 97;114;124;107 102;118;129;112 RT 43 45 25006240 Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France. CONCLUSIONS: In our cohort of patients, we observed significantly increased resistance to rilpivirine, mostly because of the E138A mutation, probably due to an E138A strain circulating in newly diagnosed men who have sex with men. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138A 125;160 130;165 25006240 Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France. Seven viral strains from seven naive male patients positive for the E138A mutation appeared in the same cluster. 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138A 68 73 25006240 Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France. The E138A mutation was the most frequent mutation associated with resistance to rilpivirine (P < 0.0001). 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138A 4 9 25006240 Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France. The prevalence of the E138A mutation tended to increase over time, from 3.6% (2/55) during the first half of 2011 to 9.3% (4/43) during the first half of 2013 (P = 0.0614). 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138A 22 27 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. The most frequent NRTI-associated mutation observed was M184V, while K103N/S was the commonest mutation at NNRTI resistance position. 2014 ISRN AIDS Abstract HIV K103N;K103S;M184V 69;69;56 76;76;61 NNRTI;NRTI 107;18 112;22 25008864 SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma. A striking multiplicative effect on the estimated risk was associated with further carriage of two non-synonymous variants, rs1800453 A>G (Asp697Gly) and rs4148880 A>G (Ile393Val), in the linked TAP1 gene (OR=10.5; 95% CI=2.54-43.6; P=0.0012). 2014 Genes and immunity Abstract HIV D697G;I393V 139;169 148;178 Asp 139 142 25008933 A mutation in the DNA polymerase accessory factor of herpes simplex virus 1 restores viral DNA replication in the presence of raltegravir. Of these, the mutations F198S in unique long region 15 (UL15; encoding the large terminase subunit), A374V in UL32 (required for DNA cleavage and packaging), V296I in UL42 (encoding the DNA polymerase accessory factor), and A224S in UL54 (encoding ICP27, an important transcriptional regulator) were introduced independently into the wild-type HSV-1(F) genome, and the recombinant viruses were tested for raltegravir resistance. 2014 Journal of virology Abstract HIV A224S;A374V;F198S;V296I 224;101;24;158 229;106;29;163 Pol 190 200 25009031 [Study on HIV viral load in plasma and drug resistance among AIDS patients receiving antiretroviral treatment in Dehong prefecture,Yunnan province]. Most mutations were related to the resistance to nucleotide reverse transcriptase inhibitors (NNRTIs) or non-nucleotide reverse transcriptase inhibitors (NNRTIs), with M184V and K103N most frequently seen. 2014 Zhonghua liu xing bing xue za zhi Abstract HIV K103N;M184V 178;168 183;173 RT;RT;NNRTI;NNRTI 60;120;94;154 81;141;100;160 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The V247I and G248A mutations that were detected before and concurrently with the potent T cell escape mutation T242N, respectively, were selected by early T cell responses. 2014 PloS one Abstract HIV G248A;T242N;V247I 14;112;4 19;117;9 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The V247I or the G248A mutation alone partially restored the fitness loss caused by the T242N mutation. 2014 PloS one Abstract HIV G248A;T242N;V247I 17;88;4 22;93;9 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Together they could fully restore the fitness of the T242N mutant to the T/F level. 2014 PloS one Abstract HIV T242N 53 58 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Two reversion mutations, V247I and I64T, were identified in Gag and Tat, respectively, but neither had measurable effect on the fitness of their cognate T/F virus. 2014 PloS one Abstract HIV I64T;V247I 35;25 39;30 Tat;Gag 68;60 71;63 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Significant correlations in detection between both methods were found for both Y181C (correlation coefficients of 0.94 [95% CI 0.91-0.96]) and K103N (0.89 [95% CI 0.84-0.92]) mutations. 2014 Journal of virological methods Abstract HIV K103N;Y181C 143;79 148;84 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The presence and percentage of Y181C and K103N drug-resistant variants in the blood of 105 subtype C HIV-infected infants who failed single-dose nevirapine prophylaxis for HIV transmission were compared using two highly sensitive genotyping methods, allele-specific PCR (AS-PCR) and ultra-deep pyrosequencing. 2014 Journal of virological methods Abstract HIV K103N;Y181C 41;31 46;36 HIV infections 101 113 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. The SDRMs included L210W (1.5%), Y181C (0.8%), and G190A (0.8%). 2014 AIDS research and therapy Abstract HIV G190A;L210W;Y181C 51;19;33 56;24;38 25036111 Systematic molecular dynamics, MM-PBSA, and ab initio approaches to the saquinavir resistance mechanism in HIV-1 PR due to 11 double and multiple mutations. Furthermore, it was observed that mutation accumulation may induce stabilization to SQV and to the flaps through enhanced HB interactions that lead to improved inhibition (e.g., accumulation of mutations in complexes containing L10I, G48V, L63P, I84V, or L90M single mutations). 2014 The journal of physical chemistry. B Abstract HIV G48V;I84V;L10I;L63P;L90M 234;246;228;240;255 238;250;232;244;259 25036111 Systematic molecular dynamics, MM-PBSA, and ab initio approaches to the saquinavir resistance mechanism in HIV-1 PR due to 11 double and multiple mutations. Herein, we extend our analysis, which includes seven double (G48V-V82A, L10I-G48V, G48V-L90M, I84V-L90M, L10I-V82A, L10I-L63P, A71V-G73S) and four multiple (L10I-L63P-A71V, L10I-G48V-V82A, G73S-I84V-L90M, L10I-L63P-A71V-G73S-I84V-L90M) SQV-HIV-1 PR mutant complexes, in an attempt to generalize our findings and formulate the main elements of the SQV resistance mechanism in the protease. 2014 The journal of physical chemistry. B Abstract HIV A71V;A71V;A71V;G48V;G48V;G48V;G48V;G73S;G73S;G73S;I84V;I84V;I84V;L10I;L10I;L10I;L10I;L10I;L10I;L63P;L63P;L63P;L90M;L90M;L90M;L90M;V82A;V82A;V82A 127;167;215;61;77;83;178;132;189;220;94;194;225;72;105;116;157;173;205;121;162;210;88;99;199;230;66;110;183 131;171;219;65;81;87;182;136;193;224;98;198;229;76;109;120;161;177;209;125;166;214;92;103;203;234;70;114;187 PR;PR 379;246 387;248 25036184 Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. 2014 AIDS (London, England) Abstract HIV K103N;Y181C 155;168 160;173 25036184 Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. 2014 AIDS (London, England) Abstract HIV K103N;Y181C 36;46 41;51 NNRTI 4 9 25036184 Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. 2014 AIDS (London, England) Abstract HIV K103N;Y181C 18;28 23;33 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. 2014 BMC infectious diseases Abstract HIV K103N 175 180 NNRTI;NNRTI 27;76 63;82 25063804 The HIV-1 integrase mutant R263A/K264A is 2-fold defective for TRN-SR2 binding and viral nuclear import. Here we report on a virus with a pair of IN mutations, IN(R263A/K264A), that significantly reduce interaction with TRN-SR2. 2014 The Journal of biological chemistry Abstract HIV I263A;R263A;K264A 58;58;64 63;63;69 IN;IN 41;55 43;57 25063804 The HIV-1 integrase mutant R263A/K264A is 2-fold defective for TRN-SR2 binding and viral nuclear import. The defect in integration of this mutant resulted in a smaller increase in the number of two-long terminal repeat circles than for virus specifically blocked at integration by raltegravir or catalytic site mutations (IN(D64N/D116N/E152Q)). 2014 The Journal of biological chemistry Abstract HIV D64N;D116N;E152Q 220;225;231 224;230;236 LTR;IN 93;217 113;219 25085657 Cost-efficient HIV-1 drug resistance surveillance using multiplexed high-throughput amplicon sequencing: implications for use in low- and middle-income countries. K101E, K103N, Y181C and M184V) were detected by GRT-NGS but not by GRT-PS. 2014 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M184V;Y181C;K101E 7;24;14;0 12;29;19;5 25089812 Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 2: discovery of novel [1,2,4]Triazolo[1,5-a]pyrimidines using a structure-guided core-refining approach. Particularly, compound 7n was the most potent inhibitor against wild-type and K103N/Y181C double resistant mutant strain of HIV-1, possessing EC50 values of 0.02 muM and 7.6 muM, respectively, which were much better than or similar to nevirapine (NVP, EC50 = 0.15 muM, 2.9 muM) and delavirdine (DLV, EC50 = 0.07 muM, >36 muM). 2014 European journal of medicinal chemistry Abstract HIV K103N;Y181C 78;84 83;89 25092296 Dimerization of HIV-1 protease occurs through two steps relating to the mechanism of protease dimerization inhibition by darunavir. Differential scanning fluorimetry indicated that PR(1-C95A) and PR(97/99) dimers were substantially less stable than PR(WT) dimers. 2014 Proc Natl Acad Sci U S A Abstract HIV C95A 54 58 PR;PR;PR 49;64;117 51;66;119 25092296 Dimerization of HIV-1 protease occurs through two steps relating to the mechanism of protease dimerization inhibition by darunavir. DRV also bound to mutant PRs containing the transframe region-added PR (TFR-PR(D25N) and TFR-PR(D25N-7AA)), whereas saquinavir did not bind to TFR-PR(D25N) or TFR-PR(D25N-7AA). 2014 Proc Natl Acad Sci U S A Abstract HIV D25N;D25N;D25N;D25N 79;96;150;166 83;100;154;170 PR;PR;PR;PR;PR;PR 25;68;76;93;147;163 28;70;78;95;149;165 25092296 Dimerization of HIV-1 protease occurs through two steps relating to the mechanism of protease dimerization inhibition by darunavir. Notably, DRV failed to bind to mutant PR containing four amino acid substitutions (V32I, L33F, I54M, and I84V) that confer resistance to DRV on HIV-1. 2014 Proc Natl Acad Sci U S A Abstract HIV I54M;I84V;L33F;V32I 95;105;89;83 99;109;93;87 PR 38 40 25092296 Dimerization of HIV-1 protease occurs through two steps relating to the mechanism of protease dimerization inhibition by darunavir. On the other hand, two termini interface PR mutants (PR(1-C95A) and PR(97/99)) took both monomeric and dimeric forms. 2014 Proc Natl Acad Sci U S A Abstract HIV C95A 58 62 PR;PR;PR 41;53;68 43;55;70 25092296 Dimerization of HIV-1 protease occurs through two steps relating to the mechanism of protease dimerization inhibition by darunavir. Recombinant wild-type PR (PR(WT)) proved to dimerize, as examined with electrospray ionization mass spectrometry; however, two active site interface PR mutants (PR(T26A) and PR(R87K)) remained monomeric. 2014 Proc Natl Acad Sci U S A Abstract HIV R87K;T26A 177;164 181;168 PR;PR;PR;PR;PR 22;26;149;161;174 24;28;151;163;176 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. Four of five patients exhibited phylogenetic evidence of a limited viral evolution between baseline and failure, with amino acid changes at drug resistance-associated positions in one: T81A emerged in Gag with M36I in the protease gene, correlating with a reduction in lopinavir susceptibility from FC 7 (95% CI 6-8.35) to FC 13 (95% CI 8.11-17.8). 2014 The Journal of antimicrobial chemotherapy Abstract HIV M36I;T81A 210;185 214;189 PR;Gag 222;201 230;204 25101529 2014 Update of the drug resistance mutations in HIV-1. The following mutations have been added to existing classes or drugs: K65E/N has been added to the bars for the nucleoside and nucleotide analogue reverse transcriptase inhibitors (nRTIs) abacavir, didanosine, emtricitabine, lamivudine, stavudine, and tenofovir; L100I has been added to the bar for the nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) rilpivirine; and F121Y has been added to the bars for the integrase strand transfer inhibitors (InSTIs) dolutegravir, elvitegravir, and raltegravir. 2014 Topics in antiviral medicine Abstract HIV F121Y;K65E;K65N;L100I 383;70;70;263 388;76;76;268 RT;RT;IN;INSTI;NNRTI;NRTI 147;326;424;462;359;181 168;347;433;468;364;186 25103592 Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. DISCUSSION: These results suggest that the selection of K70S/T and their phenotypic impact are influenced by the presence of other mutations in RT. 2014 Acta clinica Belgica Abstract HIV K70S;K70T 56;56 62;62 RT 144 146 25103592 Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. However, direct associations of K70S with mutations within the Q151M-complex and of K70T with K65R were observed. 2014 Acta clinica Belgica Abstract HIV K65R;K70S;K70T;Q151M 94;32;84;63 98;36;88;68 25103592 Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. However, the low impact on in vitro phenotype here observed, alongside with the low in vivo prevalence, the exclusive direct association with known major RTI mutations and the unknown correlation with in vivo response, do not yet necessitate the inclusion of K70S/T in drug resistance interpretation systems. 2014 Acta clinica Belgica Abstract HIV K70S;K70T 259;259 265;265 RT 154 157 25103592 Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. In this study, we investigated the in vivo selection of the HIV-1 RT mutations K70S and K70T and their in vitro effect on drug resistance and replication capacity. 2014 Acta clinica Belgica Abstract HIV K70S;K70T 79;88 83;92 RT 66 68 25103592 Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. In vitro phenotypic testing revealed only minor effects of K70R/S/T as single mutations, associated with Q151M and within the context of the Q151M-complex. 2014 Acta clinica Belgica Abstract HIV K70R;K70S;K70T;Q151M;Q151M 59;59;59;105;141 67;67;67;110;146 25103592 Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. K70R is part of the thymidine analog mutations, but also other amino acid changes have been associated with NRTI resistance, such as K70E and K70G. 2014 Acta clinica Belgica Abstract HIV K70E;K70G;K70R 133;142;0 137;146;4 NRTI 108 112 25103592 Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. RESULTS: K70S and K70T were found at a low frequency in RTI-experienced HIV-1 patients (0.10% and 0 20%). 2014 Acta clinica Belgica Abstract HIV K70S;K70T 9;18 13;22 RT 56 59 25106410 Efficacy, tolerability and virological consequences of long-term use of unboosted atazanavir plus 2 NRTIs in HIV-infected patients. At multivariate analysis a genotypic sensitivity score <= 1, atazanavir RAMs > 1 and suboptimal adherence were independently associated with virological failure; in lamivudine/emtricitabine-treated patients the presence of M184V (without other NRTI RAMs) was not associated with virological failure. 2014 Current HIV research Abstract HIV M184V 223 228 NRTI 244 248 25106410 Efficacy, tolerability and virological consequences of long-term use of unboosted atazanavir plus 2 NRTIs in HIV-infected patients. Isolated M184V in lamivudine/emtricitabine recipients was not associated with higher failure rates supporting the use of functional ATV-based dual therapies as maintenance strategies. 2014 Current HIV research Abstract HIV M184V 9 14 25106410 Efficacy, tolerability and virological consequences of long-term use of unboosted atazanavir plus 2 NRTIs in HIV-infected patients. Ten patients with virological failure presented newly selected resistance associated mutations (RAMs) for NRTIs (2/10) or ATV (4/10, one I50L). 2014 Current HIV research Abstract HIV I50L 137 141 NRTI 106 111 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. Connection sub-domain mutation, N348I and the M184V active site mutation decreases HIV-1 RT susceptibility to NNRTI, nevirapine (NVP), whereas concurrence of both mutations improves enzyme susceptibility to NVP. 2014 The protein journal Abstract HIV M184V;N348I 46;32 51;37 NNRTI;RT 110;89 115;91 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. Further, for the first time residue interaction network highlighted the structural changes due to occurrence of M184V and N348I mutations which gives a conclusive evidence of these mutations. 2014 The protein journal Abstract HIV M184V;N348I 112;122 117;127 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. Molecular dynamics simulation and enhanced post-dynamics analyses were applied to gain molecular insight into occurrence of N348I, M184V and N348I/M184V double mutations and their effect on NVP binding landscape. 2014 The protein journal Abstract HIV M184V;M184V;N348I;N348I 131;147;124;141 136;152;129;146 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. Results showed that the presence of the double mutation (N348I/M184V) ameliorates the drastic effects of connection sub-domain mutation, N348I alone on NVP binding, which correlates with experimental findings. 2014 The protein journal Abstract HIV N348I;M184V;N348I 57;63;137 62;68;142 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. The residue based fluctuation further suggested that the occurrence of N348I decreased the overall flexibility of NVP-HIV-RT complex whereas concurrence of N348I/M184V double mutation restored the conformational flexibility as compared to single mutant. 2014 The protein journal Abstract HIV M184V;N348I;N348I 162;71;156 167;76;161 RT 122 124 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. This phenomenon was further validated by the trends of binding free energy as well as the per-residue footprints which showed an increasedGbind in case of N348I/M184V double mutant as compared to N348I variant. 2014 The protein journal Abstract HIV M184V;N348I;N348I 161;155;196 166;160;201 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. This work provides the most comprehensive analysis of NVP resistance and the impact of double (N348I/M184V) mutation to date from a dynamics perspective and provides information that should prove useful for understanding the drug resistance mechanism against NVP. 2014 The protein journal Abstract HIV M184V;N348I 101;95 106;100 25107349 Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation. We showed that the binding of NVP to the NNRTI binding pocket (NNIBP) is drastically distorted in the presence of connection sub-domain mutation, N348I and may further explain the impaired motions of mutant RTs compared to the wild type. 2014 The protein journal Abstract HIV N348I 146 151 NNRTI;RT 41;207 46;210 25114163 Initiation of rilpivirine, tenofovir and emtricitabine (RPV/TDF/FTC) regimen in 363 patients with virological vigilance assessment in 'real life'. Five genotypes were determined during the follow-up, revealing three rilpivirine resistance-associated mutations: E138Q/Y181I, M230L and K101P (potentially with a K101Q intermediate). 2014 The Journal of antimicrobial chemotherapy Abstract HIV E138Q;K101P;K101Q;M230L;Y181I 114;137;163;127;120 119;142;168;132;125 25116676 Antiretroviral drug resistance and HIV-1 subtypes among treatment-naive prisoners in Kelantan, Malaysia. For RT-associated mutations, K103N was the most prevalent in sequenced samples (14.3%). 2014 Journal of infection in developing countries Abstract HIV K103N 29 34 RT 4 6 25118283 A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase. Here, we used mass spectrometry-based protein footprinting to monitor surface topology changes in full-length WT and the drug-resistant A128T mutant INs in the presence of ALLINI-2. 2014 The Journal of biological chemistry Abstract HIV A128T 136 141 IN 149 152 25118283 A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase. These experiments have identified protein-protein interactions that extend beyond the direct inhibitor binding site and which lead to aberrant multimerization of WT but not A128T IN. 2014 The Journal of biological chemistry Abstract HIV A128T 173 178 IN 179 181 25136270 Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease. Flap+ is a multidrug-resistant variant of HIV-1 protease with a combination of primary and secondary resistance mutations (L10I, G48V, I54V, V82A) and a strikingly altered thermodynamic profile for darunavir (DRV) binding relative to the wild-type protease. 2014 Journal of chemical theory and computation Abstract HIV G48V;I54V;L10I;V82A 129;135;123;141 133;139;127;145 PR;PR 48;248 56;256 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. METHODS: Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). 2014 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G190A;K103N;M184V;Y181C 252;234;275;241 257;239;280;246 NNRTI;NNRTI 62;227 67;232 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. OLA detected 24 TDR mutations (K103N: n = 13; Y181C: n = 5; G190A: n = 3; M184V: n = 3) in 15 subjects (NNRTI: n = 15; 3TC: n = 3). 2014 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G190A;K103N;M184V;Y181C 60;31;74;46 65;36;79;51 NNRTI 104 109 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. There were 97/105 (92%) patients harbouring >= 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with >= 2 TAMs; and 32 with M184V+>= 1 TAM. 2014 Journal of the International AIDS Society Abstract HIV M184V;Q151M 153;115 158;120 NRTI 95 99 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. 2014 Journal of the International AIDS Society Abstract HIV Q151M 92 97 NRTI;NRTI 150;195 182;200 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; >= 2 TAMs; or M184V+>= 1 TAM. 2014 Journal of the International AIDS Society Abstract HIV M184V;Q151M 81;53 86;58 NRTI 17 21 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. 2014 PloS one Abstract HIV M184V 9 14 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. 2014 PloS one Abstract HIV M184I;M184V;M184V 67;67;130 74;74;135 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). 2014 PloS one Abstract HIV L74V 66 71 NRTI 42 46 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. 2014 PloS one Abstract HIV M184I;M184I 54;114 59;119 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range. 2014 PloS one Abstract HIV M184V;M184I 85;0 90;5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. 2014 PloS one Abstract HIV M184I;M184V 88;99 93;104 25160759 Prevalence and patterns of drug-resistance mutations among HIV-1 patients infected with CRF07_BC strains in Sichuan province, China. Only one participant in the drug-naive group had a drug-resistance mutation (M46L), compared with 31.73% of those in whom ART had failed. 2014 Virologica Sinica Abstract HIV M46L 77 81 25160759 Prevalence and patterns of drug-resistance mutations among HIV-1 patients infected with CRF07_BC strains in Sichuan province, China. The most common mutation in the ART-failure group was M184V (35.88%), K103N (45.01%), Y181C (17.33%), and G190S/A (15.88%). 2014 Virologica Sinica Abstract HIV G190A;G190S;K103N;M184V;Y181C 106;106;70;54;86 113;113;75;59;91 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). 2014 PloS one Abstract HIV K103N;M184V 43;28 48;33 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations. 2014 PloS one Abstract HIV E33A;E33D;E44A;E44D;K65R;Q151M 118;118;126;126;112;105 124;124;132;132;116;110 25174641 Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. 2014 Journal of the International AIDS Society Abstract HIV A2059G 255 261 Pol 23 33 25174641 Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. pallidum harbouring the macrolide resistance mutation (A2058G). 2014 Journal of the International AIDS Society Abstract HIV A2058G 55 61 25174839 2 ,3 -Dialdehyde of ATP, ADP, and adenosine inhibit HIV-1 reverse transcriptase and HIV-1 replication. oATP also suppresses RT activity and replication of the HIV-1 resistant variants M184V and T215Y. 2014 Current HIV research Abstract HIV M184V;T215Y 81;91 86;96 RT 21 23 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. We previously demonstrated that a C31S substitution in Clade-C Tat dicysteine motif reduces monocyte recruitment, cytokine induction and direct neurotoxicity. 2014 PloS one Abstract HIV C31S 34 38 Tat 63 66 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. We previously reported on the genotypic differences in Tat protein between clade-C and rest of the clades showing that approximately 90% of clade-C HIV-1 Tat sequences worldwide contained this C31S polymorphism, while 99% of non-clade C isolates lacked this Tat polymorphism at C31 residue (Ranga et al. 2014 PloS one Abstract HIV C31S 193 197 Tat;Tat;Tat 55;154;258 58;157;261 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. Novel inhibitors are sought that increase potency against variants that contain the Tyr181Cys mutation. 2015 Biochimica et biophysica acta Abstract HIV Y181C 84 93 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. The Tyr181Cys binding pocket supports large, hydrophobic substituents, which is in good agreement with experiment. 2015 Biochimica et biophysica acta Abstract HIV Y181C 4 13 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We also observed that K103N, a clinically relevant NNRTI resistance mutation, does not prevent binding between efavirenz and RT-T/P but instead allows formation of a stable and productive RT-T/P-dNTP complex, possibly through disruption of the E138-K101 salt bridge. 2014 Nucleic acids research Abstract HIV K103N 22 27 NNRTI;RT;RT 51;125;188 56;127;190 25234608 Novel theoretically designed HIV-1 non-nucleoside reverse transcriptase inhibitors derived from nevirapine. A common problem with non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1 is the emergence of mutations in the HIV-1 RT, in particular Lys103 Asn (K103N) and Tyr181 Cys (Y181C), which lead to resistance to this entire class of inhibitors. 2014 Journal of molecular modeling Abstract HIV K103N;K103N;Y181C;Y181C 161;149;184;172 166;159;189;182 NNRTI;NNRTI;RT 22;71;131 58;77;133 25234608 Novel theoretically designed HIV-1 non-nucleoside reverse transcriptase inhibitors derived from nevirapine. In addition, the repulsive interaction with Cys181 in the Y181C-nevirapine complex is not present in the novel inhibitors. 2014 Journal of molecular modeling Abstract HIV Y181C 58 63 25234608 Novel theoretically designed HIV-1 non-nucleoside reverse transcriptase inhibitors derived from nevirapine. The binding modes of Mnev-1 and Mnev-2 with the wild-type HIV-1 RT and its mutants (K103N and Y181C) were suggested by molecular docking followed by 20-ns molecular dynamics (MD) simulations in explicit water of those binding complexes (HIV-1 RTs with the new inhibitors). 2014 Journal of molecular modeling Abstract HIV K103N;Y181C 84;94 90;99 RT;RT 64;243 66;246 25239368 Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C. An oligonucleotide ligation assay (OLA) designed to detect Human Immunodeficiency Virus type-1 (HIV)-drug-resistance to the nevirapine (NVP) selected mutations K103N, Y181C, V106M and G190A was used to evaluate 200 archived dried blood spots (DBS) from infected infants participating in the Zimbabwean Early Infant Diagnosis (EID) Program. 2014 Journal of virological methods Abstract HIV G190A;K103N;V106M;Y181C 184;160;174;167 189;165;179;172 25240095 Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization. Some DANAs were also active at micromolar concentrations against the K103N + Y181C resistant mutant. 2014 European journal of medicinal chemistry Abstract HIV K103N;Y181C 69;77 74;82 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Here, we have studied the impact of R263K on HIV replication capacity and the ability of HIV to establish or be reactivated from latency and/or spread through cell-to-cell transmission. 2014 Viruses Abstract HIV R263K 36 41 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. The clinical use of a novel integrase inhibitor, dolutegravir (DTG), has established hope that this compound may limit HIV persistence, since no treatment-naive patient treated with DTG has yet developed resistance against this drug, even though a R263K substitution in integrase confers low-level resistance to this drug in tissue culture. 2014 Viruses Abstract HIV R263K 248 253 IN;IN 28;270 37;279 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. A significant association was found for 13 Gag substitutions, including A431V in both subtype B and CRF01_AE. 2014 Retrovirology Abstract HIV A431V 72 77 Gag 43 46 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. K415R in subtype C and S451G in subtype B were newly identified. 2014 Retrovirology Abstract HIV S451G;K415R 23;0 28;5 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. CONCLUSION: The predisposition of subtype A(FSU) to G190S is concerning because G A is the most common HIV-1 mutation and because G190S causes higher levels of nevirapine and efavirenz resistance than K103N. 2014 AIDS (London, England) Abstract HIV G190S;G190S;K103N 52;130;201 57;135;206 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S was the most common nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation, occurring in 55 (33%) subtype A(FSU) viruses from 167 NNRTI-experienced patients compared with none of 37 CRF02_AG viruses from NNRTI-experienced patients (P < 0.001). 2014 AIDS (London, England) Abstract HIV G190S 0 5 NNRTI;NNRTI;NNRTI;NNRTI 73;155;229;26 78;160;234;61 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The next most common subtype A(FSU) NNRTI-resistance mutation, K103N, occurred in 25 (15%) viruses. 2014 AIDS (London, England) Abstract HIV K103N 63 68 NNRTI 36 41 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. Therefore, G190S results from a single G A transition: G (GGC) S (AGC) almost exclusively in subtype A(FSU) viruses. 2014 AIDS (London, England) Abstract HIV G190S 11 16 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. CONCLUSIONS: Detection of a single M41L reverse transcriptase mutation at baseline did not influence the development of resistance in vitro or virological outcome on tenofovir-containing regimens in patients belonging to a large transmission cluster. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L 35 39 RT 40 61 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. In such transmitted HIV-1 variants, the thymidine analogue mutation (TAM) M41L is frequently observed as a single resistance mutation and these viral variants often belong to phylogenetic transmission clusters. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L 72 78 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. In vivo, virological outcome of first-line regimens containing tenofovir and emtricitabine was comparable between patients diagnosed with HIV-1 harbouring M41L (n=17, 16 were part of one transmission cluster) and WT virus (n=248). 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L 155 159 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. METHODS: The impact of M41L on the development of drug resistance to tenofovir and emtricitabine was determined by extensive in vitro selection experiments and investigation of the virological outcome of patients on a first-line regimen. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L 23 27 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. Our results indicate that a high genetic barrier regimen may not be required when patients are diagnosed with HIV variants containing a single M41L mutation in reverse transcriptase. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L 143 147 RT 160 181 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. RESULTS: The presence of a single M41L mutation did not influence the selected mutational profile or the genetic barrier to resistance to tenofovir and/or emtricitabine during long-term in vitro selection experiments. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L 34 38 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. The presence of at least three TAMs, in particular patterns with M41L/L210W, impairs the efficacy of the extensively used drug tenofovir. 2015 The Journal of antimicrobial chemotherapy Abstract HIV L210W;M41L 70;65 75;69 25261422 Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance. We investigated whether the presence of a single M41L mutation at baseline influences the selection of resistance to tenofovir and emtricitabine in vitro and in vivo. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L 49 53 25270328 Genetic barrier for attachment inhibitor BMS-626529 resistance in HIV-1 B and non-B subtypes. However, for position 375, a minority of CRF02_AG sequences showed a lower genetic barrier to S375M/T resistance mutations. 2015 The Journal of antimicrobial chemotherapy Abstract HIV S375M;S375T 94;94 101;101 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Here, we show that the mutation S40F, but not the conservative mutation to Asp (S40D) or Asn (S40N), augments membrane association, K48-linked polyubiquitination, entry into the 26S proteasome, and, consequently, enhances MHC-I antigen presentation of Gag derived epitopes. 2014 Viruses Abstract HIV S40D;S40F;S40N 80;32;94 84;36;98 Asp;Gag 75;252 78;255 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. It was recently demonstrated that mutation of the highly conserved Ser-40 to Phe (S40F) disturbs CA-SP1 processing, virus morphogenesis, and infectivity. 2014 Viruses Abstract HIV S40F;S40F 82;67 86;80 SP1;Capsid 100;97 103;99 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The extended exposure of the S40F mutant to unidentified membrane-resident ubiquitin E3-ligases might trigger the polyubiquitination of Gag. 2014 Viruses Abstract HIV S40F 29 33 Gag 136 139 25281399 Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. CONCLUSIONS: Our findings identify a novel mutational pathway involving integrase mutations A49P and L234V, leading to dolutegravir resistance in a patient with the N155H raltegravir mutation. 2015 The Journal of antimicrobial chemotherapy Abstract HIV A49P;L234V;N155H 92;101;165 96;106;170 IN 72 81 25281399 Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. Here, we report the evolution of resistance to dolutegravir in a highly treatment-experienced patient harbouring the major N155H mutation consequent to raltegravir treatment failure. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H 123 128 25281399 Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. RESULTS: Five mutations (A49P, L68FL, T97A, E138K and L234V) were implicated in emergent dolutegravir resistance, with a concomitant severe compromise in viral replicative capacity. 2015 The Journal of antimicrobial chemotherapy Abstract HIV A49P;E138K;L234V;L68F;L68L;T97A 25;44;54;31;31;38 29;49;59;36;36;42 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Differences in viral infectivity by cell-associated G367R viruses were determined by the type of target cell employed, regardless which type of donor cell was used. 2014 Virology journal Abstract HIV G367R 52 57 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. G367R, that can compromise infection by cell-free virus but less severely by cell-associated virus and that does so in a cell type-dependent manner. 2014 Virology journal Abstract HIV G367R 0 5 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Interleukin 2 was able to block G367R reversion in only one of the T cell lines studied but not in the other, while phorbol 12-myristate 13-acetate (PMA) inhibited G367R reversion in all the T cell lines. 2014 Virology journal Abstract HIV G367R;G367R 32;164 37;169 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. METHODS: The ability of HIV containing an env G367R mutation in cell-free and cell-associated viruses to cause infection and to revert to wild-type was measured using several T cell lines. 2014 Virology journal Abstract HIV G367R 46 51 Env 42 45 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. RESULTS: We demonstrate that an HIV-1 variant containing a G367R substitution within the CD4 binding site of gp120 was non-infectious as free virus in culture but was infectious when infected cells were co-cultured with certain T cell lines or when cells were transfected by a relevant proviral plasmid. 2014 Virology journal Abstract HIV G367R 59 64 gp120 109 114 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. To determine factors that might potentially influence the reversion of G367R, we studied each of entry inhibitors, inhibitors of cellular endocytosis, and modulators of cell growth and activation. 2014 Virology journal Abstract HIV G367R 71 76 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004). 2014 PloS one Abstract HIV M184I;M184V 218;218 225;225 25300623 Minority HIV-1 drug-resistant mutations and prevention of mother-to-child transmission: perspectives for resource-limited countries. Y181C, K65R and thymidine analogue mutations etc.) are discussed. 2014 AIDS reviews Abstract HIV K65R;Y181C 7;0 11;5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. The nucleotide position of A2723G, A2747G and C2750T were frequent polymorphisms for the wild-type amino acids K65, K66 and D67, respectively, and 14 specimens had the D67N mutation encoded by G2748A. 2014 PloS one Abstract HIV A2723G;A2747G;C2750T;D67N;G2748A 27;35;46;168;193 33;41;52;172;199 25320302 Compensatory substitutions in the HIV-1 capsid reduce the fitness cost associated with resistance to a capsid-targeting small-molecule inhibitor. In the present study, we dissected the individual and combinatorial contributions of each of the five substitutions Q67H, K70R, H87P, T107N, and L111I to PF74 resistance, PF74 binding, and HIV-1 infectivity. 2015 Journal of virology Abstract HIV H87P;K70R;L111I;Q67H;T107N 128;122;145;116;134 132;126;150;120;139 25320302 Compensatory substitutions in the HIV-1 capsid reduce the fitness cost associated with resistance to a capsid-targeting small-molecule inhibitor. PF74 binding to HIV-1 particles was reduced by the Q67H, K70R, and T107N substitutions, consistent with the location of these positions in the inhibitor-binding pocket. 2015 Journal of virology Abstract HIV K70R;Q67H;T107N 57;51;67 61;55;72 25320302 Compensatory substitutions in the HIV-1 capsid reduce the fitness cost associated with resistance to a capsid-targeting small-molecule inhibitor. Q67H, K70R, and T107N each conferred low-level resistance to PF74 and collectively conferred strong resistance. 2015 Journal of virology Abstract HIV K70R;T107N;Q67H 6;16;0 10;21;4 25320302 Compensatory substitutions in the HIV-1 capsid reduce the fitness cost associated with resistance to a capsid-targeting small-molecule inhibitor. Replication of the 5Mut virus was markedly impaired in cultured macrophages, reminiscent of the previously reported N74D CA mutant. 2015 Journal of virology Abstract HIV N74D 116 120 Capsid 121 123 25320302 Compensatory substitutions in the HIV-1 capsid reduce the fitness cost associated with resistance to a capsid-targeting small-molecule inhibitor. The substitutions K70R and L111I impaired HIV-1 infectivity, which was partially restored by the other substitutions at positions 67 and 107. 2015 Journal of virology Abstract HIV K70R;L111I 18;27 22;32 25321623 Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir DF in antiretroviral-naive patients. Emergent substitutions were E92Q (n=7), N155H (n=3), Q148R (n=1) and T66I (n=1) in IN, and M184V/I (n=10) and K65R (n=4) in RT. 2015 Antiviral therapy Abstract HIV E92Q;K65R;M184I;M184V;N155H;Q148R;T66I 28;110;91;91;40;53;69 32;114;98;98;45;58;73 IN;RT 83;124 85;126 25321623 Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir DF in antiretroviral-naive patients. In the EFV/FTC/TDF group, virus from 14 patients (4.0%; 14/352 treated patients; 4 during weeks 96-144) developed a resistance substitution to EFV (n=14; K103N: n=13), FTC (M184V/I: n=4) or TDF (K65R: n=3). 2015 Antiviral therapy Abstract HIV K103N;K65R;M184I;M184V 154;195;173;173 159;200;181;181 25323793 Drug resistance mutations from whole blood proviral DNA among patients on antiretroviral drugs in Zimbabwe. 11 of the 108 sequences had drug resistance mutations; predominantly M184V and Y181C. 2014 Current HIV research Abstract HIV M184V;Y181C 69;79 74;84 25332224 Two-year outcome of first-line antiretroviral therapy among HIV-1 vertically-infected children in Hanoi, Vietnam. Y181C and M184V/I were the most dominant non-nucleoside and nucleoside RTI-resistance mutations, respectively (13/15, 86.7%). 2015 International journal of STD & AIDS Abstract HIV M184I;M184V;Y181C 10;10;0 17;17;5 RT 71 74 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. OBJECTIVE: To assess the presence of two major non-nucleoside reverse transcriptase inhibitors (NNRTI) drug resistance mutations (DRMs), Y181C and K103N, in minor viral quasispecies of treatment naive HIV-1 infected East-African and Swedish patients by allele-specific polymerase chain reaction (AS-PCR). 2014 PloS one Abstract HIV K103N;Y181C 147;137 152;142 NNRTI;Pol;NNRTI 47;269;96 83;279;101 HIV infections 201 215 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. RESULTS: The Y181C was detected in the minority quasispecies of six Ethiopians (6.5%), in two Caucasians (4.5%), and in one East-African (1.8%). 2014 PloS one Abstract HIV Y181C 13 18 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The K103N was detected in one East- African (1.8%), by both methods. 2014 PloS one Abstract HIV K103N 4 9 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The pol gene was analysed by standard population sequencing and by AS-PCR for the detection of Y181C and K103N. 2014 PloS one Abstract HIV K103N;Y181C 105;95 110;100 Pol 4 7 25336162 Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations. In Patient B, instead, selection of N155H could be explained by the dramatic loss of RC induced by the alternative Q148H mutation. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H 36;115 41;120 25336162 Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations. In Patient C, N155H initially emerged and was later replaced by Q148H. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H 14;64 19;69 25336162 Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations. In Patient D, Q148H rapidly emerged without appearance of N155H. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H 58;14 63;19 25336162 Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations. In the integrase sequence from Patient A, N155H conferred potent resistance coupled with a lower impact on RC than Q148H. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H 42;115 47;120 IN 7 16 25336162 Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations. In this integrase context, N155H resulted in higher RC but lower resistance than Q148H. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H 27;81 32;86 IN 8 17 25336162 Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations. RESULTS: Patients A and B experienced emergence and persistence of mutation N155H under raltegravir therapy. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H 76 81 25336162 Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations. This was the only patient for whom Q148H conferred higher RC and resistance than N155H. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H 81;35 86;40 25339776 Identification of capsid mutations that alter the rate of HIV-1 uncoating in infected cells. We found that p24(CA) mutations can significantly increase (A92E), delay (E45A and N74D), or have no effect (G94D) on the rate of uncoating and that these alterations are not due to changes in reverse transcription. 2015 Journal of virology Abstract HIV A92E;E45A;G94D;N74D 60;74;109;83 64;79;113;87 RT;p24;Capsid 193;14;18 214;17;20 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. This review focuses on K65 residue and summarizes a substantial body of biochemical and structural studies of its role in RT function and the functional consequences of the K65R mutation. 2014 Viruses Abstract HIV K65R 173 177 RT 122 124 25344807 Archived HIV-1 DNA resistance mutations to rilpivirine and etravirine in successfully treated HIV-1-infected individuals pre-exposed to efavirenz or nevirapine. Rilpivirine RAMs were detected in 41 (32%) individuals, with highest frequency for the mutations Y181C/I/V (18%), K101E/P (7%) and E138A/G/K/Q/R/S (6%) and the association L100I+K103N/S (5%). 2015 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;E138S;K101E;K101P;K103N;K103S;L100I;Y181C;Y181I;Y181V 131;131;131;131;131;131;114;114;178;178;172;97;97;97 146;146;146;146;146;146;121;121;185;185;177;106;106;106 25344810 Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P=0.0455) and T215Y (P=0.0455). 2015 The Journal of antimicrobial chemotherapy Abstract HIV M41L;T215Y 79;99 83;104 25348045 Appearance of drug resistance-associated mutations in human immunodeficiency virus type 1 protease and reverse transcriptase derived from drug-treated Indonesian patients. In contrast, 37.7% (20/53) of the participants had one or more major drug resistance mutations in the RT genes, predominantly M184V (28.3%), K103N (11.3%), and thymidine analogue mutations (TAMs) (20.8%). 2015 AIDS research and human retroviruses Abstract HIV K103N;M184V 141;126 146;131 RT 102 104 25348535 The R262K substitution combined with H51Y in HIV-1 subtype B integrase confers low-level resistance against dolutegravir. Although viral replication was not affected and enzyme efficiency was impaired by the addition of R262K to H51Y, there was an overall increase in the level of biochemical drug resistance against DTG. 2015 Antimicrobial agents and chemotherapy Abstract HIV H51Y;R262K 107;98 111;103 25348535 The R262K substitution combined with H51Y in HIV-1 subtype B integrase confers low-level resistance against dolutegravir. In a recent selection study with DTG, using a virus bearing the H51Y substitution in integrase, the emergence of an R to K substitution at position 262 (R262K) was observed. 2015 Antimicrobial agents and chemotherapy Abstract HIV H51Y;R262K 64;153 68;158 IN 85 94 25348535 The R262K substitution combined with H51Y in HIV-1 subtype B integrase confers low-level resistance against dolutegravir. The combination of H51Y and R262K substitutions slightly decreased susceptibility to DTG (fold change = 1.87) in cell-based resistance assays. 2015 Antimicrobial agents and chemotherapy Abstract HIV H51Y;R262K 19;28 23;33 25348535 The R262K substitution combined with H51Y in HIV-1 subtype B integrase confers low-level resistance against dolutegravir. We showed that the addition of R262K to H51Y decreased recombinant integrase strand transfer activity but improved integrase DNA-binding affinity, compared to wild-type or H51Y-containing enzymes. 2015 Antimicrobial agents and chemotherapy Abstract HIV H51Y;H51Y;R262K 40;172;31 44;176;36 IN;IN 67;115 76;124 25350960 Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus atazanavir+ritonavir+emtricitabine/tenofovir DF in antiretroviral-naive patients. Emergent substitutions were E92Q, N155H, or Q148R (n = 2 each) and T66I or T97A (n = 1 each) in IN and M184V/I (n = 7) and K65R (n = 1) in RT. 2014 HIV clinical trials Abstract HIV E92Q;K65R;M184I;M184V;N155H;Q148R;T66I;T97A 28;123;103;103;34;44;67;75 32;127;110;110;39;49;71;79 IN;RT 96;139 98;141 25350960 Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus atazanavir+ritonavir+emtricitabine/tenofovir DF in antiretroviral-naive patients. In the ATV+RTV+FTC/TDF group, HIV-1 from 2 patients (0.6%; 2/355 treated patients; both at week 144) developed the resistance substitution M184V/I in RT. 2014 HIV clinical trials Abstract HIV M184I;M184V 139;139 146;146 RT 150 152 25355312 Derivatives of mesoxalic acid block translocation of HIV-1 reverse transcriptase. The K65R mutation in HIV-1 RT, which reduces affinity to PFA, increases affinity to CPHM. 2015 The Journal of biological chemistry Abstract HIV K65R 4 8 RT 27 29 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. Besides the key resistance mutations K65R, Q151M, and M184V, we identified a novel mutation, V111I, in the polymerase domain. 2015 Journal of virology Abstract HIV K65R;M184V;Q151M;V111I 37;54;43;93 41;59;48;98 Pol 107 117 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. Biochemical assays demonstrate that V111I restores the polymerization defects of the K65R and Q151M viruses but negatively affects the fidelity of the HIV-2 RT enzyme. 2015 Journal of virology Abstract HIV K65R;Q151M;V111I 85;94;36 89;99;41 RT 157 159 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. IMPORTANCE: Mutation V111I in the HIV-2 reverse transcriptase enzyme was identified in patients failing therapies containing nucleoside analogues. 2015 Journal of virology Abstract HIV V111I 21 26 RT 40 61 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. Molecular dynamics simulations were performed to analyze the structural changes mediated by V111I. 2015 Journal of virology Abstract HIV V111I 92 97 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. This mutation was significantly associated with mutations K65R and Q151M. 2015 Journal of virology Abstract HIV K65R;Q151M 58;67 62;72 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. This showed that V111I changed the flexibility of the 110-to-115 loop region, which may affect deoxynucleoside triphosphate (dNTP) binding and polymerase activity. 2015 Journal of virology Abstract HIV V111I 17 22 Pol 143 153 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. We show that the V111I change does not strongly affect the sensitivity of HIV-2 to nucleoside analogues but increases the fitness of viruses with drug resistance mutations K65R and Q151M. 2015 Journal of virology Abstract HIV K65R;Q151M;V111I 172;181;17 176;186;22 25355888 Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses. We show that V111I does not strongly affect drug susceptibility but increases the replication capacity of the K65R and Q151M viruses. 2015 Journal of virology Abstract HIV K65R;Q151M;V111I 110;119;13 114;124;18 25355911 Structural basis and distal effects of Gag substrate coevolution in drug resistance to HIV-1 protease. To understand the molecular basis of this protease-substrate coevolution, we solved the crystal structures of drug resistant I50V/A71V HIV-1 protease with p1-p6 substrates bearing coevolved mutations. 2014 Proc Natl Acad Sci U S A Abstract HIV A71V;I50V 130;125 134;129 PR;PR;Gag 42;141;158 50;149;160 25358434 Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket. Some compounds displayed submicromolar activity against the K103N/Y181C resistant mutant strain (such as compound DCS-a4, EC50= 0.65 mum). 2015 Chemical biology & drug design Abstract HIV K103N;Y181C 60;66 65;71 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. The decrease in binding free energies for PR2 relative to PR1 is found to arise from the reduction of the van der Waals interactions induced by the structural adjustment of the triple mutant V32I, I47V and V82I. 2014 Scientific reports Abstract HIV I47V;V32I;V82I 197;191;206 201;195;210 PR;PR 42;58 45;61 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. However, there were no significant differences in cognitive performances between individuals with the C31S motif versus those without the C31S substitution. 2014 Journal of neurovirology Abstract HIV C31S;C31S 102;138 106;142 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Previous animal studies have identified a C31S residue substitution in the C30C31 dicysteine motif of the Tat protein that is associated with reduced neurovirulence in clade C human immunodeficiency virus (HIV). 2014 Journal of neurovirology Abstract HIV C31S 42 46 Tat 106 109 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Results confirm that the C31S dicysteine motif substitution of the Tat protein does not appreciably moderate neuropsychological outcomes in clade C. 2014 Journal of neurovirology Abstract HIV C31S 25 29 Tat 67 70 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. The present study investigated the impact of the Tat C30C31S genetic substitution among individuals residing in South Africa infected with clade C HIV that either exhibited the C30C31 motif (n = 128) or the C31S motif (n = 46). 2014 Journal of neurovirology Abstract HIV C31S 207 211 Tat 49 52 25367908 Antiviral characteristics of GSK1265744, an HIV integrase inhibitor dosed orally or by long-acting injection. GSK1265744 demonstrated activity against SDM clones containing the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature variants (FC less than 6.1), while these mutants had a high FC in the EC50 for RAL (11 to >130). 2015 Antimicrobial agents and chemotherapy Abstract HIV G140S;N155H;Q148H;Q148K;Y143R 120;109;126;102;95 125;114;131;107;100 25371739 Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia. The most common point mutations, which result in Thr55Ala and Pro57Ser amino acid substitutions, were not detected in the Pneumocystis jirovecii sampled from the HIV-negative patients. 2014 Experimental and therapeutic medicine Abstract HIV P57S;T55A 62;49 70;57 25371739 Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia. Two other point mutations, which result in nonsynonymous mutation, Asp90Asn and Glu98Lys, were identified in P. 2014 Experimental and therapeutic medicine Abstract HIV D90N;E98K 67;80 75;88 Asp 67 70 25373632 Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase. Although Elvitegravir (EVG) is a newly developed antiretrovirals drug to treat the acquired immunodeficiency syndrome (AIDS), drug resistance has already been found in clinic, such as E92Q/N155H and Q148H/G140S. 2014 Interdisciplinary sciences, computational life sciences Abstract HIV E92Q;G140S;N155H;Q148H 184;205;189;199 188;210;194;204 AIDS;AIDS 83;119 117;123 25373632 Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase. As full length crystal structure for HIV-1 integrase is still unsolved, we herein use the crystal structure of the full length prototype foamy virus (PFV) in complex with virus DNA and inhibitor Elvitegravir as a template to construct the wild type and E92Q/N155H mutant system of HIV-1 integrase. 2014 Interdisciplinary sciences, computational life sciences Abstract HIV E92Q;N155H 253;258 257;263 IN;IN 43;287 52;296 25373632 Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase. Molecular dynamic simulations was used to revel the binding mode and the drug resistance of the EVG ligand in E92Q/N155H. 2014 Interdisciplinary sciences, computational life sciences Abstract HIV E92Q;N155H 110;115 114;120 25373632 Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase. Several important interactions were discovered between the mutated residues and the residues in the active site of the E92Q/N155H double mutant pattern, and cross correlation and clustering methods were used for detailed analysis. 2014 Interdisciplinary sciences, computational life sciences Abstract HIV E92Q;N155H 119;124 123;129 25378497 Mutations in HIV-1 envelope that enhance entry with the macaque CD4 receptor alter antibody recognition by disrupting quaternary interactions within the trimer. For this purpose, we examined how two independent mutations that enhance mCD4-mediated entry, A204E and G312V, impact antibody recognition in the context of seven different parental HIV-1 Env proteins from diverse subtypes. 2015 Journal of virology Abstract HIV A204E;G312V 94;104 99;109 Env 188 191 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Although the K42E mutation conferred functional gains to integrase mutant viral reverse transcription and integration, only the integration boost depended on the engineered LEDGF/p75 mutant. 2014 Molecular therapy. Methods & clinical development Abstract HIV K42E 13 17 IN;RT 57;80 66;101 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Both K42E and initial reverse-charge mutations in integrase negatively impacted reverse transcription and integration, yet when combined together boosted viral transduction efficiency to ~75% of the wild-type vector in a manner dependent on a complementary LEDGF/p75 variant. 2014 Molecular therapy. Methods & clinical development Abstract HIV K42E 5 9 IN;RT 50;80 59;101 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Here we describe the selection and characterization of the K42E gain-of-function mutation in HIV-1 integrase, which greatly improves the efficiency of this system. 2014 Molecular therapy. Methods & clinical development Abstract HIV K42E 59 63 IN 99 108 25385110 In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. In the resistance selection of subtype A and C viruses, similar mutation development pathways were detected, in which a V106A or V106M mutant was also the starting virus in the pathways. 2015 Antimicrobial agents and chemotherapy Abstract HIV V106A;V106M 120;129 125;134 25385110 In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. In the resistance selection of subtype B virus with DOR, a V106A mutant virus led to two mutation pathways, followed by the emergence separately of either F227L or L234I. 2015 Antimicrobial agents and chemotherapy Abstract HIV F227L;L234I;V106A 155;164;59 160;169;64 25385110 In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. Mutations that are commonly associated with RPV and EFV in clinical settings were also identified in subtype B viruses such as the E138K and K103N mutants, respectively, in this in vitro resistance selection study. 2015 Antimicrobial agents and chemotherapy Abstract HIV E138K;K103N 131;141 136;146 25385110 In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. When the replication capacity of the V106A mutant was compared with that of the wild-type (WT) virus, the mutant virus was 4-fold less fit than the WT virus. 2015 Antimicrobial agents and chemotherapy Abstract HIV V106A 37 42 25386009 High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen. RESULTS: Among the 92 patients analysed, 32 (35%) showed resistance to dolutegravir, in most cases associated with the combination of Q148H/R/K with G140S/A mutations. 2015 The Journal of antimicrobial chemotherapy Abstract HIV G140A;G140S;Q148H;Q148K;Q148R 149;149;134;134;134 156;156;143;143;143 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Based on the MD simulations, N43D mutation affects not only the stability of C34 binding, but also the binding energy of the inhibitor C34. 2014 PloS one Abstract HIV N43D 29 33 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Because N43D mutation may also affect the stable conformation of 6-HB, we introduced S138A second mutation into CHR of gp41 and determined the impact of this mutation. 2014 PloS one Abstract HIV N43D;S138A 8;85 12;90 gp41 119 123 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Because the conformational stability of 6-HB is important to HIV-1 infection, we suggested a hypothetical mechanism for the drug resistance: N43D single mutation not only impact the binding of inhibitor, but also affect the affinity between NHR and CHR of gp41, thus may reduce the rate of membrane fusion; compensatory mutation S138A would induce greater hydrophobic interactions between NHR and CHR, and render the CHR more compatible to NHR than inhibitors. 2014 PloS one Abstract HIV N43D;S138A 141;329 145;334 gp41 256 260 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In addition, mutations on CHR (C-terminal heptad repeat) accompanied NHR mutations of gp41 are noted in many cases, like N43D/S138A double mutation. 2014 PloS one Abstract HIV N43D;S138A 121;126 125;131 gp41 86 90 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In this work, we explored the drug resistant mechanism of N43D mutation and the role of S138A second mutation in drug resistance. 2014 PloS one Abstract HIV N43D;S138A 58;88 62;93 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The binding modes of the wild type gp41 and the two mutants, N43D and N43D/S138A, with the HIV-1 fusion inhibitor C34, a 34-residue peptide mimicking CHR of gp41, were carried out by using molecular dynamics simulations. 2014 PloS one Abstract HIV N43D;N43D;S138A 61;70;75 65;74;80 gp41;gp41 35;157 39;161 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Through the comparative analysis of MD results of the N43D mutant and the N43D/S138A mutant, we found that CHR with S138A mutation shown more favorable affinity to NHR. 2014 PloS one Abstract HIV N43D;N43D;S138A;S138A 54;74;79;116 58;78;84;121 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. CONCLUSIONS: Secondary mutations to R263K following selection with DTG have all led to diminished viral and enzymatic fitness, helping to explain why resistance to DTG in previously drug-naive subjects has never been observed. 2014 Journal of the International AIDS Society Abstract HIV R263K 36 41 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. Conversely, combinations of R263K together with multiple resistance mutations for RAL and/or EVG at positions 92,143, 148 and 155 resulted in even further diminished enzymatic activity that may be incompatible with viral survival. 2014 Journal of the International AIDS Society Abstract HIV R263K 28 33 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. In contrast, a R263K mutation that confers low-level resistance (3-4 fold) to DTG has been selected by DTG in culture. 2014 Journal of the International AIDS Society Abstract HIV R263K 15 20 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. Modelling of the 3-dimensional structure of integrase suggests that R263K is located in a region that may not permit further mutagenesis if secondary mutations at H51Y or E138K are also present. 2014 Journal of the International AIDS Society Abstract HIV E138K;H51Y;R263K 171;163;68 176;167;73 IN 44 53 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. Moreover, integrase that contains R263K together with substitutions at positions 92, 143, 148 and 155 may be enzymatically inactive. 2014 Journal of the International AIDS Society Abstract HIV R263K 34 39 IN 10 19 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. Our group has ascribed the absence of resistance to DTG to the high fitness cost exacted by the R263K mutation and an inability of HIV to generate compensatory mutations. 2014 Journal of the International AIDS Society Abstract HIV R263K 96 101 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. RESULTS: The R263K mutation alone conferred an approximate 3-fold level of resistance to DTG and a 40% loss in viral replicative capacity and recombinant integrase activity. 2014 Journal of the International AIDS Society Abstract HIV R263K 13 18 IN 154 163 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. Secondary mutations selected at positions H51Y or E138K did not individually affect either enzyme activity or DTG resistance, but the combination of R263K together with H51Y or E138K increased DTG resistance to about 7-fold accompanied by a 75% loss in each of viral replication capacity, and both in vitro and in vivo integrase activity. 2014 Journal of the International AIDS Society Abstract HIV E138K;E138K;H51Y;H51Y;R263K 50;177;42;169;149 55;182;46;173;154 IN 320 329 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. The use of the R263K-containing virus to select for resistance to RAL led to the appearance of RAL-containing mutations but the loss of R263K. 2014 Journal of the International AIDS Society Abstract HIV R263K;R263K 15;136 31;141 25394027 The R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound. We also selected for resistance against raltegravir (RAL) using viruses containing the R263K mutation. 2014 Journal of the International AIDS Society Abstract HIV R263K 87 92 25394119 Determinants of HIV-1 drug resistance in treatment-naive patients and its clinical implications in an antiretroviral treatment program in Cameroon. The M184V mutation was the most frequently detected nucleoside reverse transcriptase inhibitor (NRTI) mutation (n=18) followed by TAMs (n=5) and multi-NRTI resistance mutations (n=4). 2014 Journal of the International AIDS Society Abstract HIV M184V 4 9 NRTI;NRTI;NRTI 52;96;151 84;100;155 25394119 Determinants of HIV-1 drug resistance in treatment-naive patients and its clinical implications in an antiretroviral treatment program in Cameroon. The most commonly observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance mutations were K103N (n=10), Y181C (n=7), and G190A (n=6). 2014 Journal of the International AIDS Society Abstract HIV G190A;K103N;Y181C 139;108;122 144;113;127 NRTI;NNRTI 31;75 63;80 25397436 Using dried blood spots collected under field condition to determine HIV-1 diversity and drug resistance mutations in resource limited Tanzania. The mutations detected were Y181C (n=8), K103 (n=4) and G190A (n=1), conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), and M184V (n=1), conferring resistance to lamivudine and emtricitabine. 2014 Journal of the International AIDS Society Abstract HIV G190A;M184V;Y181C 56;156;28 61;161;33 NNRTI;NNRTI 94;143 130;149 25397452 Transmitted drug resistance in women with intrapartum HIV-1 diagnosis: a pilot epidemiological survey in Buenos Aires, Argentina. In 12 patients a genotypic resistance test was performed: two (16.7%) had WHO RAMs corresponding to K103N mutation in both cases, conferring high-level resistance to nevirapine (NVP) and efavirenz. 2014 Journal of the International AIDS Society Abstract HIV K103N 100 105 25397482 Detection of resistance mutations and CD4 slopes in individuals experiencing sustained virological failure. M184V) were explored, but none were significantly associated with the CD4 slope; for these comparisons, a Bonferroni-corrected p-value level was 0.003. 2014 Journal of the International AIDS Society Abstract HIV M184V 0 5 25397483 HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M. Mutations selected in HIV-O can be classified as follows: (1) mutations described for HIV-M such as T97A, Q148R, V151A/I (RAL), T66I, E92Q, E157Q (EVG) and M50I, R263K (DTG) and (2) signature mutations for HIV-O. 2014 Journal of the International AIDS Society Abstract HIV E157Q;E92Q;M50I;Q148R;R263K;T66I;T97A;V151A;V151I 140;134;156;106;162;128;100;113;113 145;138;160;111;167;132;104;120;120 25397483 HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M. None of the HIV-O viruses selected either N155H or Y143C. 2014 Journal of the International AIDS Society Abstract HIV N155H;Y143C 42;51 47;56 25397483 HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M. not described in HIV-M) F121C (HIV-O/B for RAL), V75I (HIV-O/A for RAL) and S153V (HIV-O/A for DTG). 2014 Journal of the International AIDS Society Abstract HIV F121C;S153V;V75I 22;76;49 29;81;53 25397483 HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M. Only the HIV-O/Div selected the Q148R mutation for RAL and R263K+M50I for DTG, as previously described for HIV-M. 2014 Journal of the International AIDS Society Abstract HIV M50I;Q148R;R263K 65;32;59 69;37;64 25397483 HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M. positions L74I, S153A, G163Q and T206S. 2014 Journal of the International AIDS Society Abstract HIV G163Q;L74I;S153A;T206S 23;10;16;33 28;14;21;38 25397483 HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M. The selection of the specific S153V mutation could be explained at the nucleotide level: HIV-O at this position contains an alanine and substitution of alanine to valine (153AGGC 153VGTC) is easier than substitution of alanine to tyrosine (153AGGC 153YTAC), with only a transversion needed instead of one transition plus one transversion. 2014 Journal of the International AIDS Society Abstract HIV S153V 30 35 25397487 Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks. Crucially, we found that both K103N, E138Q are associated with transmission networking within men having sex with men (MSM) and intravenous drug user (IDU) local networks. 2014 Journal of the International AIDS Society Abstract HIV E138Q;K103N 37;30 42;35 25397487 Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks. Phylodynamic analyses revealed that the exponential growth for K103N network started in 2009 (Figure 1) and for the E138Q in 2010. 2014 Journal of the International AIDS Society Abstract HIV E138Q;K103N 116;63 121;68 25397487 Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks. The K103N network included seropositives across Greece, while the latter only from the recent IDU outbreak in Athens metropolitan area (1). 2014 Journal of the International AIDS Society Abstract HIV K103N 4 9 25397487 Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks. The prevalence of K103N and E138Q were significantly increased during 2003-2013. 2014 Journal of the International AIDS Society Abstract HIV E138Q;K103N 28;18 33;23 25397490 Viral escape in the CNS with multidrug-resistant HIV-1. The resistance testing of the CSF-HIV-1 RNA showed two NRTI resistance-associated mutations (M184V and K65R) and one NNRTI resistance-associated mutation (K103N). 2014 Journal of the International AIDS Society Abstract HIV K103N;K65R;M184V 155;103;93 160;107;99 NNRTI;NRTI 117;55 122;59 25397491 Characterization of natural polymorphic sites of the HIV-1 integrase before the introduction of HIV-1 integrase inhibitors in Germany. E157Q considered by HIVdb, ANRS, and GRADE algorithms was the most frequent resistance-associated polymorphism with an overall prevalence of 2.4%. 2014 Journal of the International AIDS Society Abstract HIV E157Q 0 5 25397493 Use of deep sequencing data for routine analysis of HIV resistance in newly diagnosed patients. RESULTS: Using VisibleChek for analysis, we were able to describe the detection of any mutation using Sanger in 37/88 patients, with a total number of 50 Stanford >=5 mutations, K103N and E138A being the most prevalent (n=4). 2014 Journal of the International AIDS Society Abstract HIV E138A;K103N 188;178 193;183 25397494 New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy. Here, we present a case of virological failure in a DTG treated patient based on N155H mutation background. 2014 Journal of the International AIDS Society Abstract HIV N155H 81 86 25397494 New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy. However, there is only rare data available about the impact of N155H in the context of secondary site integrase mutations. 2014 Journal of the International AIDS Society Abstract HIV N155H 63 68 IN 102 111 25397494 New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy. In June 2013, after S119R, N155H and E157Q mutations in viral integrase were detected, the patient received DTG, and RAL was stopped. 2014 Journal of the International AIDS Society Abstract HIV E157Q;N155H;S119R 37;27;20 42;32;25 IN 62 71 25397494 New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy. Since N155H alone is described not to contribute sufficient resistance to DTG, there seems to be a need to re-check viruses with N155H plus minor mutations (like T97A, S119R, S147G and E157Q) potentially contributing to DTG resistance. 2014 Journal of the International AIDS Society Abstract HIV E157Q;N155H;N155H;S119R;S147G;T97A 185;6;129;168;175;162 190;11;134;173;180;166 25397494 New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy. The here documented strain became resistant to DTG without carrying mutations at the described positions 140 and 148, but in the context of integrase N155H. 2014 Journal of the International AIDS Society Abstract HIV N155H 150 155 IN 140 149 25397494 New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy. The impact of a single N155H mutation to DTG resistance is described to be minor. 2014 Journal of the International AIDS Society Abstract HIV N155H 23 28 25397494 New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy. Two new mutations T97A and S147G in the integrase and no other new resistance associated mutations in protease and reverse transcriptase in comparison to the sample analyzed in June 2013 were detected. 2014 Journal of the International AIDS Society Abstract HIV S147G;T97A 27;18 32;22 IN;PR;RT 40;102;115 49;110;136 25397495 Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey. However, thymidine analogue resistance mutations (TAMs) determined two distinct genotypic profiles in the HIV-1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q, and T215F. 2014 Journal of the International AIDS Society Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 174;186;186;180;147;141;199;157 178;193;193;184;152;145;204;162 RT 112 133 25397495 Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey. RESULTS: The patients had TDRMs to NRTIs (K65R, M184V), NNRTIs (K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L) and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M). 2014 Journal of the International AIDS Society Abstract HIV G190A;G190E;G190S;I54V;I84V;K101E;K103N;K103S;K65R;L76V;L90M;M184V;M46L;N83D;V82L;V82T;Y181C;Y181I;Y188H;Y188L 80;80;80;124;150;64;71;71;42;130;156;48;118;144;136;136;91;91;100;100 89;89;89;128;154;69;78;78;46;134;160;53;122;148;142;142;98;98;107;107 NNRTI;NRTI;PI 56;35;113 62;40;116 25397495 Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey. Three patients had NRTIs+NNRTs resistance mutations (M184V+K103N) as multi-class drug resistance. 2014 Journal of the International AIDS Society Abstract HIV K103N;M184V 59;53 64;58 NRTI 19 24 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. Ultra-deep sequencing of integrase showed the selection of Q148R, E138K+Q148K, and N155H variants and phenotypic raltegravir resistance was demonstrated. 2014 Journal of the International AIDS Society Abstract HIV E138K;N155H;Q148K;Q148R 66;83;72;59 71;88;77;64 IN 25 34 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. Ultra-deep sequencing showed selection of N155H, followed by Q95K and V151I variants and phenotypic raltegravir resistance was demonstrated. 2014 Journal of the International AIDS Society Abstract HIV N155H;Q95K;V151I 42;61;70 47;65;75 25397502 Time to virologic failure for patients taking their first antiretroviral regimen and the subsequent resistance profiles. No new PI or II mutations were identified and one new NNRTI (Y181C) mutation was identified. 2014 Journal of the International AIDS Society Abstract HIV Y181C 61 66 NNRTI;PI 54;7 59;9 25397502 Time to virologic failure for patients taking their first antiretroviral regimen and the subsequent resistance profiles. Three patients taking PI-based regimens developed NRTI mutations (M184V, M184I, T215Y). 2014 Journal of the International AIDS Society Abstract HIV M184I;M184V;T215Y 73;66;80 78;71;85 NRTI;PI 50;22 54;24 25397504 Early clinical response and presence of viral resistant minority variants: a proof of concept study. One patient without baseline resistance selected for M184I+E138K+T215I (NGS) after four months of TDF/FTC/RPV therapy. 2014 Journal of the International AIDS Society Abstract HIV E138K;M184I;T215I 59;53;65 64;58;70 25397504 Early clinical response and presence of viral resistant minority variants: a proof of concept study. Single mutations E138K (two cases) and M184V in three distinct patients and V90I+G190E; M184V+A98S; Y215F+V118I+T215I; L210S+T215I+F227L; and A62V+D67G+K70N+188H in the remaining five subjects. 2014 Journal of the International AIDS Society Abstract HIV A62V;A98S;D67G;E138K;F227L;G190E;K70N;L210S;M184V;M184V;T215I;T215I;V118I;V90I;Y215F 142;94;147;17;131;81;152;119;39;88;112;125;106;76;100 146;98;151;22;136;86;156;124;44;93;117;130;111;80;105 25397505 Resistance mutations in protease gene at baseline are not related to virological failure in patients treated with darunavir/ritonavir monotherapy. Twenty-two patients (29%) had some mutations in protease gene, 10 patients (13%) had major mutations and 1 patient had some mutations of resistance for darunavir (I64V). 2014 Journal of the International AIDS Society Abstract HIV I64V 163 167 PR 48 56 25397528 Gag drug resistance mutations in HIV-1 subtype C patients, failing a protease inhibitor inclusive treatment regimen, with detectable lopinavir levels. The following mutations that are associated with PI exposure were present in the data set: G62R (n=6), H219Q (n=11), S737T (n=8), I389T (n=8) and Q474L (n=7). 2014 Journal of the International AIDS Society Abstract HIV G62R;H219Q;I389T;Q474L;S737T 91;103;130;146;117 95;108;135;151;122 PI 49 51 25397528 Gag drug resistance mutations in HIV-1 subtype C patients, failing a protease inhibitor inclusive treatment regimen, with detectable lopinavir levels. These mutations are K436R (n=4), I437V (n=1), L449P (n=5), R452K (n=4) and P453L\T (n=9). 2014 Journal of the International AIDS Society Abstract HIV I437V;K436R;L449P;P453L;R452K 33;20;46;75;59 38;25;51;80;64 25397531 Efficacy of a dual therapy based on darunavir/ritonavir and etravirine in ART-experienced patients. Thirty-nine patients had NNRTI resistance mutations [28 K103N (37.3%), 6 Y181I/C (8%), 3 G190A (4%)] and 29 patients had >=1 primary PI mutations. 2014 Journal of the International AIDS Society Abstract HIV Y181I 73 80 NNRTI;PI 25;133 30;135 25397545 Lamivudine plus darunavir boosted with ritonavir as simplification dual regimen in HIV-infected patients. In eight cases, a previous resistance test showed two to seven secondary mutations in the protease gene, without resistance to DRV/r (one patient with the I84V mutation). 2014 Journal of the International AIDS Society Abstract HIV I84V 155 159 PR 90 98 25397553 Randomized trial of DRV/r or LPV/r QD monotherapy vs maintaining a PI/r-based antiretroviral regimen in persons with suppressed HIV replication. A GRT was performed in 6/14 patients (one not amplifiable; four without mutations; one showed E138A). 2014 Journal of the International AIDS Society Abstract HIV E138A 94 99 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. 2014 Retrovirology Abstract HIV T242N 152 157 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. BACKGROUND: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. 2014 Retrovirology Abstract HIV T242N 124 129 Gag 133 136 HIV infections 140 154 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. 2014 Retrovirology Abstract HIV T242N 98 103 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. 2014 Retrovirology Abstract HIV N242T;T242N;T242N 91;26;264 96;31;269 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. RESULTS: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. 2014 Retrovirology Abstract HIV T242N 13 18 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. 2014 Retrovirology Abstract HIV T242N 56 61 25408842 Picomolar Inhibitors of HIV-1 Reverse Transcriptase: Design and Crystallography of Naphthyl Phenyl Ethers. Promising compounds are reported that show midpicomolar activity against the wild-type virus and sub-20 nM activity against viral variants bearing Tyr181Cys and Lys103Asn mutations in HIV-RT. 2014 ACS medicinal chemistry letters Abstract HIV K103N;Y181C 161;147 170;156 RT 188 190 25411830 Low rate of transmitted drug resistance may indicate low access to antiretroviral treatment in Maranhao State, northeast Brazil. Only single class mutations to NRTI (M184V; T215S) or NNRTI (K103S/N) were detected. 2015 AIDS research and human retroviruses Abstract HIV K103N;K103S;M184V;T215S 61;61;37;44 68;68;42;49 NNRTI;NRTI 54;31 59;35 25414202 G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. Indeed, the F121Y mutation was more resistant to raltegravir than to dolutegravir. 2015 The Journal of antimicrobial chemotherapy Abstract HIV F121Y 12 17 25414202 G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. Interestingly, the F121Y mutation, but not the G118R mutation, displayed differential resistance to raltegravir and dolutegravir. 2015 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 19;47 24;52 25414202 G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. METHODS: Both the F121Y and G118R mutations were introduced by site-directed mutagenesis into the pNL4.3 backbone and studied in cell-based and in vitro assays. 2015 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 18;28 23;33 25414202 G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. The aim of this study was to characterize the susceptibility of two mutations, F121Y and G118R, originally described in patients failing raltegravir-containing regimens, to dolutegravir and raltegravir, and then to compare the resistance of these mutations with that of other well-known mutations involved in raltegravir resistance. 2015 The Journal of antimicrobial chemotherapy Abstract HIV F121Y;G118R 79;89 84;94 2541558 Role of the cysteine-rich region of HIV tat protein on its trans-activational ability. Substitution of either Cys22 with Gly, or Cys34-Gln-Val-Cys with His-Gln-Val-His, and deletion behind Lys50 of the tat protein caused a drastic loss in its activity. 1989 Virus genes Abstract HIV C22G 23 37 Tat 115 118 25418038 Indolylarylsulfones carrying a heterocyclic tail as very potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. Docking studies showed that the methyl group of (R)-11 points toward the cleft created by the K103N mutation, different from the corresponding group of (S)-11. 2014 Journal of medicinal chemistry Abstract HIV K103N 94 99 25421485 Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors. The amino acid substitutions E138Q/R, Y181I/V, and M230L conferred high-level resistance to ETR, while K101P and Y181I/V conferred high-level resistance to RPV. 2015 Antimicrobial agents and chemotherapy Abstract HIV E138Q;E138R;K101P;M230L;Y181I;Y181I;Y181V;Y181V 29;29;103;51;38;113;38;113 36;36;108;56;45;120;45;120 25421485 Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors. The low-level resistance to RPV and ETR conferred by E138K was not significantly enhanced in the presence of M184V/I, unlike for EFV and NVP. 2015 Antimicrobial agents and chemotherapy Abstract HIV E138K;M184I;M184V 53;109;109 58;116;116 25421485 Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors. The more common EFV/NVP resistance-associated substitutions, such as K103N, V106M, and G190A, had no major impact on ETR or RPV susceptibility. 2015 Antimicrobial agents and chemotherapy Abstract HIV G190A;K103N;V106M 87;69;76 92;74;81 25421485 Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors. These included N348I and T369I, amino acid changes in the connection domain that are not generally assessed during resistance testing. 2015 Antimicrobial agents and chemotherapy Abstract HIV N348I;T369I 15;25 20;30 25421485 Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors. Y181C, a major NNRTI resistance-associated amino acid substitution, caused decreased susceptibility to ETR and, to a lesser extent, RPV when combined with other mutations. 2015 Antimicrobial agents and chemotherapy Abstract HIV Y181C 0 5 NNRTI 15 20 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. CONCLUSIONS: Our findings reveal a distinct mechanism of resistance for the H171T IN mutation to ALLINI BI-D and indicate a previously undescribed role of the His171 side chain for binding the inhibitor. 2014 Retrovirology Abstract HIV H171T 76 81 IN 82 84 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. However, the H171T IN substitution only modestly affected IN-LEDGF/p75 binding and allowed HIV-1 containing this substitution to replicate at near WT levels. 2014 Retrovirology Abstract HIV H171T 13 18 IN;IN 19;58 21;60 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. RESULTS: We have investigated the effects of one of the most prevalent substitutions, H171T IN, selected under increasing pressure of ALLINI BI-D. 2014 Retrovirology Abstract HIV H171T 86 91 IN 92 94 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The x-ray crystal structures of BI-D binding to WT and H171T IN CCD dimers coupled with binding free energy calculations revealed the importance of the Ndelta- protonated imidazole group of His171 for hydrogen bonding to the BI-D tert-butoxy ether oxygen and establishing electrostatic interactions with the inhibitor carboxylic acid, whereas these interactions were compromised upon substitution to Thr171. 2014 Retrovirology Abstract HIV H171T 55 60 IN 61 63 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. These results correlated with ~84-fold reduced affinity for BI-D binding to recombinant H171T IN CCD protein compared to its wild type (WT) counterpart. 2014 Retrovirology Abstract HIV H171T 88 93 IN 94 96 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Virus containing the H171T IN substitution exhibited an ~68-fold resistance to BI-D treatment in infected cells. 2014 Retrovirology Abstract HIV H171T 21 26 IN 27 29 25424878 Requirement of HIV-1 Vif C-terminus for Vif-CBF-beta interaction and assembly of CUL5-containing E3 ligase. RESULTS: Here, through immunoprecipitation analysis of Vif C-terminal truncated mutants of various lengths, we identified that CBF-beta binding requires not only certain amino acids (G126A, E134A, Y135A and G138A) in the HCCH region but also the HCCH motif itself, which also affects the Vif-mediated suppression of APOBEC3G/APOBEC3F (A3G/A3F). 2014 BMC microbiology Abstract HIV E134A;G126A;G138A;Y135A 190;183;207;197 195;188;212;202 Vif;Vif 55;288 58;291 25427100 Update on HIV-1 acquired and transmitted drug resistance in Africa. The major nucleoside reverse transcriptase inhibitor mutation in all four African regions was M184V. 2015 AIDS reviews Abstract HIV M184V 94 99 NRTI 10 42 25428920 Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon . The M184V (n = 18) and K103N (n = 10) mutations were most common. 2015 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M184V 23;4 28;9 25453342 A stably expressed llama single-domain intrabody targeting Rev displays broad-spectrum anti-HIV activity. We found that Nb(190) was able to suppress the function of these Rev variants except for the K20N mutant, which was present in only 0.7% of HIV-1 sequence populations (n = 4632). 2014 Antiviral research Abstract HIV K20N 93 97 Rev 65 68 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Here, we compared six HIV vectors carrying different integrases, either wild type or with different mutations (D64V, D167H, Q168A, K186Q+Q214L+Q216L, and RRK262-264AAH) shown to modify integrase enzymatic activity, oligomerization, or interaction with key cellular cofactor of HIV DNA integration as LEDGF/p75 or TNPO3. 2014 Molecular therapy. Nucleic acids Abstract HIV D167H;D64V;K186Q;Q168A;Q214L;Q216L 117;111;131;124;137;143 122;115;136;129;142;148 IN;IN 53;185 63;194 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Surprisingly and most interestingly, we report that an integrase carrying the D167H substitution improves vector transduction efficiency and integration in both HEK-293T and primary CD34+ cells. 2014 Molecular therapy. Nucleic acids Abstract HIV D167H 78 83 IN 55 64 25472016 Genetic barrier to resistance for dolutegravir. Unexpectedly, a mutation rarely selected in this scenario (R263K) induces a fitness cost that prevents HIV-1 from evading drug pressure, and accumulation of further secondary mutations does not occur and has not been able to compensate the replication capacity deficit in the aftermath of the appearance of a single drug resistance mutation. 2015 AIDS reviews Abstract HIV R263K 59 64 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001). 2014 PloS one Abstract HIV K103N 13 18 25482475 In vitro selection of HIV-1 CRF08_BC variants resistant to reverse transcriptase inhibitors. As expected, M184I alone, or with V90I or D67N, decreased 3TC susceptibility by over 1,000-fold. 2015 AIDS research and human retroviruses Abstract HIV D67N;M184I;V90I 42;13;34 46;18;38 25482475 In vitro selection of HIV-1 CRF08_BC variants resistant to reverse transcriptase inhibitors. EFV-associated variations contained two initial mutations (L100I and Y188C) and three other mutations (V106L, F116Y, and A139V). 2015 AIDS research and human retroviruses Abstract HIV A139V;F116Y;L100I;V106L;Y188C 121;110;59;103;69 126;115;65;108;74 25482475 In vitro selection of HIV-1 CRF08_BC variants resistant to reverse transcriptase inhibitors. Initial mutations, in combination with other previously reported substitutions (K20R, D67N, V90I, K101R/E, V106I/A, V108I, F116L, E138R, A139V, V189I, G190A, D218E, E203K, H221Y, F227L, N348I, and T369I) or novel mutations (V8I, S134N, C162Y, L228I, Y232H, E396G, and D404N), developed during NVP selection. 2015 AIDS research and human retroviruses Abstract HIV A139V;C162Y;D218E;D404N;D67N;E138R;E203K;E396G;F116L;F227L;G190A;H221Y;K101E;K101R;K20R;L228I;N348I;S134N;T369I;V106A;V106I;V108I;V189I;V8I;V90I;Y232H 137;236;158;268;86;130;165;257;123;179;151;172;98;98;80;243;186;229;197;107;107;116;144;224;92;250 142;241;163;273;90;135;170;262;128;184;156;177;105;105;84;248;191;234;202;114;114;121;149;227;96;255 25482475 In vitro selection of HIV-1 CRF08_BC variants resistant to reverse transcriptase inhibitors. Phenotypic analyses showed that E138R, Y181C, and G190A contributed high-level resistance to NVP, while L100I and V106L significantly reduced virus susceptibility to EFV. 2015 AIDS research and human retroviruses Abstract HIV E138R;G190A;L100I;V106L;Y181C 32;50;104;114;39 37;55;109;119;44 25482475 In vitro selection of HIV-1 CRF08_BC variants resistant to reverse transcriptase inhibitors. Three different resistance patterns led by initial mutations of Y181C, E138G, and Y188C were detected after the selection with NVP. 2015 AIDS research and human retroviruses Abstract HIV E138G;Y181C;Y188C 71;64;82 76;69;87 25482475 In vitro selection of HIV-1 CRF08_BC variants resistant to reverse transcriptase inhibitors. Y188C was 20-fold less sensitive to both NVP and EFV. 2015 AIDS research and human retroviruses Abstract HIV Y188C 0 5 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. Eight (8) patients had NRTI resistance mutations with NAMS M184V (54.2%) and K65R (8.4%) mutations being the highest followed by TAMs T215Y and K70R (12.5%). 2014 BMC research notes Abstract HIV K65R;K70R;M184V;T215Y 77;144;59;134 81;148;64;139 NRTI 23 27 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. However, for NRTI two patients had TAM T215Y. 2014 BMC research notes Abstract HIV T215Y 39 44 NRTI 13 17 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. In addition, among patients failing second-line (20), six patients (30%) had NNRTI resistance; two patients on K103N and G190A mutations while V106A, Y184V, A98G, Y181C mutations per patient were also detected. 2014 BMC research notes Abstract HIV A98G;G190A;K103N;V106A;Y181C;Y184V 157;121;111;143;163;150 161;126;116;148;168;155 NNRTI 77 82 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. M184V mutation occurred in one patient. 2014 BMC research notes Abstract HIV M184V 0 5 25487655 Structural Basis of Why Nelfinavir-Resistant D30N Mutant of HIV-1 Protease Remains Susceptible to Saquinavir. Although anti-HIV-1 protease drugs nelfinavir (NFV) and saquinavir (SQV) share common functional groups, D30N is a major resistance mutation against NFV but remains susceptible to SQV. 2015 Chemical biology & drug design Abstract HIV D30N 105 109 PR 20 28 25487655 Structural Basis of Why Nelfinavir-Resistant D30N Mutant of HIV-1 Protease Remains Susceptible to Saquinavir. Structural analysis showed that SQV forms two direct hydrogen bonds with the main chain atoms of the residues Asp29 and Asp30 that are not observed in the D30N-NFV complex. 2015 Chemical biology & drug design Abstract HIV D30N 155 159 Asp;Asp 110;120 113;123 25487655 Structural Basis of Why Nelfinavir-Resistant D30N Mutant of HIV-1 Protease Remains Susceptible to Saquinavir. These could be the reasons why D30N is not a drug resistance mutation against SQV. 2015 Chemical biology & drug design Abstract HIV D30N 31 35 25487655 Structural Basis of Why Nelfinavir-Resistant D30N Mutant of HIV-1 Protease Remains Susceptible to Saquinavir. We have determined the crystal structure of D30N mutant-tethered HIV-1 protease in complex with SQV to 1.79 A resolution. 2015 Chemical biology & drug design Abstract HIV D30N 44 48 PR 71 79 25488402 Modulation of HIV protease flexibility by the T80N mutation. An analysis of T80N WAXS data shows that this variant is significantly more rigid than the WT across all length scales. 2015 Proteins Abstract HIV T80N 15 19 25488402 Modulation of HIV protease flexibility by the T80N mutation. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. 2015 Proteins Abstract HIV T80N 13 17 25488402 Modulation of HIV protease flexibility by the T80N mutation. To investigate the potential influence of the T80N mutation on HIVp flexibility, wide-angle X-ray scattering (WAXS) data was measured for a series of HIVp variants. 2015 Proteins Abstract HIV T80N 46 50 25492654 [Investigation of HIV-1 primary drug resistance mutations in antiretroviral therapy-naive cases]. Detected mutations were as follows: M41L, K70E, M184V, L210W and T215C/D/S, responsible for nucleoside RT inhibitor (NRTI) resistance; K103N/S and Y181C, responsible for non-nucleoside RT inhibitor (NNRTI) resistance; M46L and L90M, responsible for protease inhibitor (PI) resistance. 2014 Mikrobiyoloji bulteni Abstract HIV K103N;K103S;K70E;L210W;L90M;M184V;M41L;M46L;T215C;T215D;T215S;Y181C 135;135;42;55;227;48;36;218;65;65;65;147 142;142;46;60;231;53;40;222;74;74;74;152 PR;NNRTI;NRTI;PI;RT;RT 249;199;117;269;103;185 257;204;121;271;105;187 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. In accordance, we found that the gp120 levels in the envelope of N616Q mutant gp41 strains NL4.3, IIIB and HE were severely decreased. 2014 Retrovirology Abstract HIV N616Q 65 70 gp120;gp41;Env 33;78;53 38;82;61 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. In contrast, N616Q gp41 mutant HIV-1ADA contained gp120 levels similar to the gp120 levels in WT HIV-1ADA virus. 2014 Retrovirology Abstract HIV N616Q 13 18 gp41;gp120;gp120 19;50;78 23;55;83 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals. 2014 Retrovirology Abstract HIV K103N;K103N 53;64 58;69 NNRTI 38 43 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). 2014 Retrovirology Abstract HIV M184I;M184T;M184V 196;196;196 205;205;205 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naive population. 2014 Retrovirology Abstract HIV M184I;M184V 28;28 35;35 NRTI 15 19 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs. 2014 Retrovirology Abstract HIV K103N 203 208 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. 2014 Retrovirology Abstract HIV M184I;M184V 0;0 7;7 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. 2014 Retrovirology Abstract HIV K103N 29 34 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Fifty-seven samples had at least one TDR-associated mutation, mainly including L10I/V (6.3%), A71L/T/V (6.3%), V179D/E (5.4%), and V106I (2.7%), with different distributions of TDR-associated mutations by different HIV-1 subtypes and by each year. 2014 BMC infectious diseases Abstract HIV A71L;A71T;A71V;L10I;L10V;V106I;V179D;V179E 94;94;94;79;79;131;111;111 102;102;102;85;85;136;118;118 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Moreover, eight significant co-variation pairs were found between TDR-associated mutations (V179D/E) and seven overlapping polymorphisms in subtype CRF01_AE. 2014 BMC infectious diseases Abstract HIV V179D;V179E 92;92 99;99 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. A 1.9 A resolution crystal structure was solved for PRG48T/L89M bound with saquinavir (PRG48T/L89M-SQV) and compared to the crystal structure of PRWT bound with saquinavir (PRWT-SQV). 2015 Biochemistry Abstract HIV L89M;L89M 59;94 63;98 PR;PR 52;87 54;89 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. HIV drug resistance continues to emerge; consequently, there is an urgent need to develop next generation antiretroviral therapeutics.1 Here we report on the structural and kinetic effects of an HIV protease drug resistant variant with the double mutations Gly48Thr and Leu89Met (PRG48T/L89M), without the stabilizing mutations Gln7Lys, Leu33Ile, and Leu63Ile. 2015 Biochemistry Abstract HIV G48T;L33I;L63I;L89M;L89M;Q7K 257;337;351;287;270;328 265;345;359;291;278;335 PR;PR 199;280 207;282 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Kinetic analyses reveal that PRG48T/L89M and PRWT share nearly identical Michaelis-Menten parameters; however, PRG48T/L89M exhibits weaker binding for IDV (41-fold), SQV (18-fold), APV (15-fold), and NFV (9-fold) relative to PRWT. 2015 Biochemistry Abstract HIV L89M;L89M 36;118 40;122 PR;PR 29;111 31;113 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Our mechanism for PRG48T/L89M-SQV drug resistance proposes that a defective hydrophobic sliding mechanism results in modified conformational dynamics of the protease. 2015 Biochemistry Abstract HIV L89M 25 29 PR;PR 157;18 165;20 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. PRG48T/L89M-SQV assumes a more open conformation relative to PRWT-SQV, as illustrated by the downward displacement of the fulcrum and elbows and weaker interatomic flap interactions. 2015 Biochemistry Abstract HIV L89M 7 11 PR 0 2 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. PRG48T/L89M-SQV has an enlarged active site resulting in the loss of a hydrogen bond in the S3 subsite from Gly48 to P3 of SQV, as well as less favorable hydrophobic packing interactions between P1 Phe of SQV and the S1 subsite. 2015 Biochemistry Abstract HIV L89M 7 11 PR 0 2 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. We also show that the Leu89Met mutation disrupts the hydrophobic sliding mechanism by causing a redistribution of van der Waals interactions in the hydrophobic core in PRG48T/L89M-SQV. 2015 Biochemistry Abstract HIV L89M;L89M 175;22 179;30 PR 168 170 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). CONCLUSIONS: An HIV-1 variant carrying a conservative S40N exchange in p6(Gag) is fully functional in tissue culture demonstrating that neither S40 nor its phosphorylation are required for HIV-1 release and maturation. 2014 Retrovirology Abstract HIV S40N 54 58 Gag;Gag 74;71 77;73 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). HIV-1 derivatives with a conservative S40N or a non-conservative S40F exchange were produced. 2014 Retrovirology Abstract HIV S40F;S40N 65;38 69;42 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Previously published studies showed that an S40F exchange in p6(Gag) severely affected virus infectivity, while we had reported that mutation of all phosphorylatable residues in p6(Gag) had only minor effects. 2014 Retrovirology Abstract HIV S40F 44 48 Gag;Gag;Gag;Gag 64;181;61;178 67;184;63;180 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). The phenotype of the S40F mutation appears to be caused by the bulky hydrophobic residue introduced into a flexible region. 2014 Retrovirology Abstract HIV S40F 21 25 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). The S40F substitution severely affected virus maturation and infectivity as reported before, while the S40N exchange caused no functional defects and the variant was fully infectious in T-cell lines and primary T-cells. 2014 Retrovirology Abstract HIV S40F;S40N 4;103 8;107 25537532 Synthesis and biological evaluation of DAPY-DPEs hybrids as non-nucleoside inhibitors of HIV-1 reverse transcriptase. A series of new DAPY-DPEs hybrids, combined the important pharmacophores of DAPYs and DPEs, has been synthesized and biologically evaluated for their anti-HIV activities against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 and HIV-2 strain ROD in MT-4 cell cultures. 2015 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 225;231 230;236 RT 214 216 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. NGS enabled the detection of additional minor variant DRMs in the infant with K103N. 2015 Journal of clinical virology Abstract HIV K103N 78 83 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. RESULTS: Of 15 infants, tested at a median age of 3.4 months after birth, 2 (13%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (K103N and Y181C) by bulk sequencing, whereas PGM detected 4 (26%) and MiSeq 5 (30%). 2015 Journal of clinical virology Abstract HIV K103N;Y181C 147;157 153;162 NNRTI;NNRTI 86;134 122;139 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. Taken together, W427S gp120 could induce higher level of specific binding and neutralizing Ab production that may be associated with the reduction of non-specific Tfh but strengthening of the memory Tfh. 2014 PloS one Abstract HIV W427S 16 21 gp120 22 27 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. The modified W427S gp120 elicits higher levels of specific binding antibodies as well as nAbs though it produces less Tfh cells. 2014 PloS one Abstract HIV W427S 13 18 gp120 19 24 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. We constructed a gp120 mutant W427S of an HIV-1 primary R5 strain and examined its ability in the elicitation of Ab and the production of Tfh by immunization of BALB/c mice. 2014 PloS one Abstract HIV W427S 30 35 gp120 17 22 25552724 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. Additionally, in integrase inhibitor-experienced patients, only R263K and other previously known integrase resistance substitutions have been reported. 2015 Journal of virology Abstract HIV R263K 64 69 IN;IN 17;97 26;106 25552724 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. By characterizing the G118R substitution, this work also preemptively defines parameters for a potentially important pathway in some non-B HIV subtype viruses treated with dolutegravir and will aid in the inhibition of such a virus, if detected. 2015 Journal of virology Abstract HIV G118R 22 27 25552724 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. In cell-free experiments, the impacts of the H51Y and E138K substitutions on resistance and enzyme efficiency, when present with G118R, were highly dependent on viral subtype. 2015 Journal of virology Abstract HIV E138K;G118R;H51Y 54;129;45 59;134;49 25552724 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. Subtype B and circulating recombinant form AG (CRF02_AG) clonal viruses encoding G118R-bearing integrases were severely restricted in their viral replication capacity, and G118R/E138K-bearing viruses had various levels of resistance to dolutegravir, raltegravir, and elvitegravir. 2015 Journal of virology Abstract HIV E138K;G118R;G118R 178;81;172 183;86;177 IN 95 105 25552724 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. The G118R substitution, previously identified with MK-2048 and raltegravir, may represent the initial substitution in a dolutegravir resistance pathway. 2015 Journal of virology Abstract HIV G118R 4 9 25552724 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. We have found that subtype C integrase proteins have a low enzymatic cost associated with the G118R substitution, mostly at the strand transfer step of integration, compared to either subtype B or recombinant CRF02_AG proteins. 2015 Journal of virology Abstract HIV G118R 94 99 IN 29 38 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. Finally, the RT mutant Y115F displayed lower discrimination against rNTPs due to its increase in binding affinity for non-canonical rNTPs. 2015 Antiviral research Abstract HIV Y115F 23 28 RT 13 15 25558077 Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients. The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;N155S;Q148G;Q148H;Q148K;Q148R;Y143C;Y143G;Y143H;Y143R;Y143S 42;42;59;59;59;59;83;83;83;83;83 49;49;70;70;70;70;96;96;96;96;96 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Although the second binding of TMC114 with flap does increase binding energy for the mutants (V32I-2T and M46L-2T), the considerable entropy loss results in the lower binding Gibbs free energies. 2015 Journal of molecular graphics & modelling Abstract HIV M46L;V32I 106;94 110;98 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. For the single binding (1T) the less binding affinity can be attributed to the entropic loss for both V32I-1T and M46L-1T. 2015 Journal of molecular graphics & modelling Abstract HIV M46L;V32I 114;102 118;106 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. However, for some mutants such as V32I and M46L the TMC114 can bind not only to the active cavity but also to the groove of the flexible flaps. 2015 Journal of molecular graphics & modelling Abstract HIV M46L;V32I 43;34 47;38 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. MM-PBSA calculations explain the binding free energies unfavorable for the M46L and V32I mutants as compared to the WT. 2015 Journal of molecular graphics & modelling Abstract HIV M46L;V32I 75;84 79;88 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The conformational dynamics of HIV-1-pr and the binding of TMC114 to the WT, V32I and M46L mutants were investigated with all-atom molecular dynamic (MD) simulation. 2015 Journal of molecular graphics & modelling Abstract HIV M46L;V32I 86;77 90;81 PR 37 39 25568209 Human immunodeficiency virus type 1 employs the cellular dynein light chain 1 protein for reverse transcription through interaction with its integrase protein. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV-1IN(Q53A/Q252A)) exhibited impaired reverse transcription. 2015 Journal of virology Abstract HIV Q252A;Q53A 63;58 68;62 RT;IN 90;33 111;35 25568209 Human immunodeficiency virus type 1 employs the cellular dynein light chain 1 protein for reverse transcription through interaction with its integrase protein. Through further investigations, we have also detected relatively smaller amounts of particulate CA in DYNLL1-KD cells or in infections with HIV-1IN(Q53A/Q252A) mutant virus. 2015 Journal of virology Abstract HIV Q252A;Q53A 153;148 158;152 Capsid 96 98 25573121 [The efficacy of antiviral therapy and drug resistance analysis among HIV/AIDS patients with heroin addiction in Guangxi Zhuang Autonomous Region]. Among the patients who received antiviral treatment, the mutation frequency of M184V/I, T215Y/F, L210W and T69N/S in heroin abuser group were significantly higher than that in never using drug group (14.9% (11/74) vs 4.4% (3/68), 12.2% (9/74) vs 1.5% (1/68), 12.2% (9/74) vs 1.5% (1/68) and 10.8% (8/74) vs 1.5% (1/68) respectively) (P < 0.05). 2014 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV L210W;M184I;M184V;T215F;T215Y;T69N;T69S 97;79;79;88;88;107;107 102;86;86;95;95;113;113 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. CONCLUSIONS: With multiple approaches and analyses we identified structural and dynamical determinants associated with the changes found in the binding affinity of the M36I variant. 2014 BMC genomics Abstract HIV M36I 168 172 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. The observed impact of M36I, suggest that combination with other non-B subtype polymorphisms, could lead to major effects on the interaction with the 12 known cleavage sites, which should impact the virion maturation. 2014 BMC genomics Abstract HIV M36I 23 27 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. RESULTS: We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. 2014 Retrovirology Abstract HIV K103N;M41L;M46L 107;99;146 112;103;150 RT;PR;RT 116;154;139 137;162;141 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. The majority of site-directed mutations (M46I/M46L in protease and M41L, M41L + T215Y and K103N in RT) decreased viral replicative capacity; only protease mutation L90M did not hamper viral replication. 2014 Retrovirology Abstract HIV M46I;K103N;L90M;M41L;M41L;M46L;T215Y 41;90;164;67;73;46;80 45;95;168;71;77;50;85 PR;PR;RT 54;146;99 62;154;101 25576600 Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012. Additionally, we observed that the transmitted high-fitness-cost mutation M184V was positively associated with the PVL of nonresponding patients carrying M184V (RR, 1.50 per 100 increase in PVL; P < .001). 2015 The Journal of infectious diseases Abstract HIV M184V;M184V 74;154 79;159 25576600 Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012. Such association was absent for K103N (RR, 1.00 per 100 increase in PVL; P = .99) and negative for L90M (RR, 0.75 per 100 increase in PVL; P = .022). 2015 The Journal of infectious diseases Abstract HIV K103N;L90M 32;99 37;103 25576600 Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012. The association between the prevalence of TDR mutations and population viral load (PVL) among treated patients during 1997-2011 was estimated with Poisson regression for all TDR mutations and individually for the most frequent resistance mutations against each drug class (ie, M184V/L90M/K103N). 2015 The Journal of infectious diseases Abstract HIV K103N;L90M;M184V 288;283;277 293;287;282 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Eleven polymorphic mutations (G16E, K20I, L23P, E35D, M36I, N37D/S/T, R57K, L63P, and V82I) were detected in the PR that were subtype or CRF specific while only three mutations (D123N, I135T, and I135V) were identified in the RT. 2015 AIDS research and human retroviruses Abstract HIV D123N;E35D;G16E;I135T;I135V;K20I;L23P;L63P;M36I;N37D;N37S;N37T;R57K;V82I 178;48;30;185;196;36;42;76;54;60;60;60;70;86 183;52;34;190;201;40;46;80;58;68;68;68;74;90 PR;RT 113;226 115;228 25583721 Simian-tropic HIV as a model to study drug resistance against integrase inhibitors. Here, we used a T-cell-tropic SIV/HIV recombinant virus in which the capsid and vif regions of HIV-1 were replaced with their SIV counterparts (simian-tropic HIV-1 [stHIV-1](SCA,SVIF)) to study the impact of a number of drug resistance substitutions in the integrase coding region at positions E92Q, G118R, E138K, Y143R, S153Y, N155H, and R263K on drug resistance, viral infectivity, and viral replication capacity. 2015 Antimicrobial agents and chemotherapy Abstract HIV E138K;E92Q;G118R;N155H;R263K;S153Y;Y143R 307;294;300;328;339;321;314 312;298;305;333;344;326;319 IN;Capsid;Vif 257;69;80 266;75;83 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. Both monomeric and dimeric forms of wild type and V260E mutant are highly stable during the simulated period. 2015 Journal of computer-aided molecular design Abstract HIV V260E 50 55 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. However, the stabilizing pi-stacking interaction between Trp243 and Trp243' at the dimer interface is highly disturbed in CTD-V260E (>6 A apart). 2015 Journal of computer-aided molecular design Abstract HIV V260E 126 131 PI 25 27 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. In addition to this, the dynamics of CTD-wild type and V260E monomers at 498 K was analyzed to elucidate the effect of V260E mutation on CTD folding. 2015 Journal of computer-aided molecular design Abstract HIV V260E;V260E 55;119 60;124 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. In general, V260E mutation affects both multimerization and protein folding with a pronounced effect on protein folding rather than multimerization. 2015 Journal of computer-aided molecular design Abstract HIV V260E 12 17 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. In this study, molecular dynamics simulation techniques were used to unveil the effect of V260E mutation on isolated CTD monomer and dimer. 2015 Journal of computer-aided molecular design Abstract HIV V260E 90 95 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. Increase in SASA and reduction in the number of contacts in CTD-V260E during simulation highlights the instability caused by the mutation. 2015 Journal of computer-aided molecular design Abstract HIV V260E 64 69 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. Mutational studies on isolated CTD and full-length IN have reported V260E mutant as either homo-dimerization defective or affecting the stability and folding of CTD. 2015 Journal of computer-aided molecular design Abstract HIV V260E 68 73 IN 51 53 25586721 Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase. The loss in entropy for dimerization is -30 and -25 kcal/mol for CTD-wt and CTD-V260E respectively signifying a weak hydrophobic interaction and its perturbation in CTD-V260E. 2015 Journal of computer-aided molecular design Abstract HIV V260E;V260E 80;169 85;174 25587020 Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. 2015 The Journal of infectious diseases Abstract HIV M184I;M184V 208;208 214;214 25587020 Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. METHODS: Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing. 2015 The Journal of infectious diseases Abstract HIV K65R;K65R;K70E;M184I;M184V 158;184;193;167;167 163;189;197;173;173 25588315 Estimation of the Binding Free Energy of AC1NX476 to HIV-1 Protease Wild Type and Mutations Using Free Energy Perturbation Method. Residues Asp25-A, Asp29-A, Asp30-A, Ile47-A, Gly48-A, and Val50-A from chain A, and Asp25-B from chain B play a crucial role in the ligand binding. 2015 Chemical biology & drug design Abstract HIV D29A;G48A 18;45 25;52 Asp;Asp;Asp;Asp 9;18;27;84 12;21;30;87 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Compared to wild type hDAT, Y470A and K92M but not Y88F reduced the maximal velocity of [(3)H]DA uptake without changes in the Km. 2015 Journal of neuroimmune pharmacology Abstract HIV K92M;Y470A;Y88F 38;28;51 42;33;55 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Moreover, only Y470A and K92M enhanced DA efflux relative to wild type hDAT, suggesting mutations of these residues differentially modulate transporter conformational transitions. 2015 Journal of neuroimmune pharmacology Abstract HIV K92M;Y470A 25;15 29;20 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The present study examined the functional influences of other substitutions at tyrosine470 (Y470F and Y470A) and tyrosine88 (Y88F) and lysine92 (K92M), two other relevant residues for Tat binding to hDAT, in Tat-induced inhibitory effects on DA transport. 2015 Journal of neuroimmune pharmacology Abstract HIV K92M;Y470A;Y470F;Y88F 145;102;92;125 149;107;98;129 Tat;Tat 184;208 187;211 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Through integrated computational modeling and pharmacological studies, we have demonstrated that mutation of tyrosine470 (Y470H) of human DAT (hDAT) attenuates Tat-induced inhibition of DA uptake by changing the transporter conformational transitions. 2015 Journal of neuroimmune pharmacology Abstract HIV Y470H 122 127 Tat 160 163 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Y470F, Y470A, Y88F and K92M attenuated zinc-induced increase of [(3)H]WIN35,428 binding. 2015 Journal of neuroimmune pharmacology Abstract HIV K92M;Y470A;Y88F;Y470F 23;7;14;0 27;12;18;5 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Y88F and K92M enhanced IC50 values for DA inhibition of [(3)H]DA uptake and [(3)H]WIN35,428 binding but decreased IC50 for cocaine and GBR12909 inhibition of [(3)H]DA uptake, suggesting that these residues are critical for substrate and these inhibitors. 2015 Journal of neuroimmune pharmacology Abstract HIV K92M;Y88F 9;0 13;4 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Y88F, K92M and Y470A attenuated Tat-induced inhibition of DA transport, implicating the functional relevance of these residues for Tat binding to hDAT. 2015 Journal of neuroimmune pharmacology Abstract HIV K92M;Y470A;Y88F 6;15;0 10;20;4 Tat;Tat 32;131 35;134 25626145 Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches. Additionally, 7d demonstrated weak activity against the double mutant HIV-1 strain (K103N + Y181C), and was more efficient than NVP in a RT inhibition assay. 2015 European journal of medicinal chemistry Abstract HIV K103N;Y181C 84;92 90;97 RT 137 139 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. Genetic mutations were also isolated that induce resistance to ARV such as M184V, Y115F, K103N, Y181C, V179E, and G190A. 2015 Global health action Abstract HIV G190A;K103N;M184V;V179E;Y115F;Y181C 114;89;75;103;82;96 119;94;80;108;87;101 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. A modelling study using the server SWISS-MODEL was conducted to explore the possible structure-related drug resistance mechanism of the mutation D404N. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N 145 150 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. CONCLUSIONS: These results indicate that D404N is a novel NNRTI-associated mutation in the HIV-1 subtype CRF08_BC and provides information valuable for the monitoring of clinical RTI resistance. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N 41 46 NNRTI;RT 58;179 63;182 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. Double mutations Y181C/D404N and Y181C/H221Y significantly reduced susceptibility to NNRTIs. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N;H221Y;Y181C;Y181C 23;39;17;33 28;44;22;38 NNRTI 85 91 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. METHODS: Mutation D404N, alone or together with the other reported mutations, was introduced into an HIV-1 CRF08_BC subtype infectious clone by site-directed mutagenesis. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N 18 23 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. RESULTS: Single mutations D404N and H221Y conferred low-level resistance to nevirapine, efavirenz, rilpivirine and zidovudine. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N;H221Y 26;36 31;41 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. The modelling study suggested that the D404N mutation might abolish the hydrogen bonds between residues 404 and K30 in p51 or K431 in p66, leading to impaired RT subunit structure and enhanced drug resistance. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N 39 44 RT 159 161 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. The most pronounced resistance to NNRTIs was observed with the triple mutation Y181C/D404N/H221Y. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N;H221Y;Y181C 85;91;79 90;96;84 NNRTI 34 40 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. This work was designed to determine the effects of a novel mutation, D404N, in the connection subdomain of RT of HIV-1 CRF08_BC subtype on drug resistance, viral replication capacity (RC) and RT activity. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N 69 74 RT;RT 107;192 109;194 25637519 A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs. Virus containing D404N as the only mutation displayed ~50% RC compared with the WT virus. 2015 The Journal of antimicrobial chemotherapy Abstract HIV D404N 17 22 25649362 HIV-1 transmitted drug resistance and genetic diversity among patients from Piaui State, Northeast Brazil. Dual class resistance mutations to NRTI and NNRTI were observed: T215L (NRTI), Y188L (NNRTI) and T215N (NRTI), F227L (NNRTI). 2015 Journal of medical virology Abstract HIV F227L;T215L;T215N;Y188L 111;65;97;79 116;70;102;84 NNRTI;NNRTI;NNRTI;NRTI;NRTI;NRTI 44;86;118;35;72;104 49;91;123;39;76;108 25649362 HIV-1 transmitted drug resistance and genetic diversity among patients from Piaui State, Northeast Brazil. Singleton mutations to protease-inhibitor/PI, nucleoside-reverse-transcriptase-inhibitor/NRTI or non-nucleoside-reverse-transcriptase-inhibitor/NNRTI predominated (8/10): PI mutations (M46L, V82F, L90M); NRTI mutations (M41L, D67N) and NNRTI mutations (K103N/S). 2015 Journal of medical virology Abstract HIV D67N;K103N;K103S;L90M;M41L;M46L;V82F 226;253;253;197;220;185;191 230;260;260;201;224;189;195 RT;RT;PR;NNRTI;NNRTI;NRTI;NRTI;PI;PI 57;112;23;144;236;89;204;42;171 78;133;31;149;241;93;208;44;173 25650933 Alteration of the langerin oligomerization state affects Birbeck granule formation. Although the W264R mutation causes CRD global unfolding, the F241L mutation does not affect the overall structure and gp120 (surface HIV-1 glycoprotein of 120 kDa) binding capacities of isolated Lg-CRD. 2015 Biophysical journal Abstract HIV F241L;W264R 61;13 66;18 gp120 118 123 25650933 Alteration of the langerin oligomerization state affects Birbeck granule formation. As demonstrated by small-angle x-ray scattering comparative analysis of wild-type and mutant forms, the F241L mutation perturbs the oligomerization state and the global architecture of Lg-ECD. 2015 Biophysical journal Abstract HIV F241L 104 109 25650933 Alteration of the langerin oligomerization state affects Birbeck granule formation. Beyond the change of residue itself, the F241L mutation induces relocation of the K200 side chain also located within the interface between protomers of trimeric Lg-ECD, thereby explaining the defective oligomerization of mutant Lg. 2015 Biophysical journal Abstract HIV F241L 41 46 25650933 Alteration of the langerin oligomerization state affects Birbeck granule formation. We investigated at the molecular level the impact of two CRD mutations, W264R and F241L, on langerin structure, function, and BG assembly using a combination of biochemical and biophysical approaches. 2015 Biophysical journal Abstract HIV F241L;W264R 82;72 87;77 25653132 Epidemiological and molecular characteristics of HIV infection among money boys and general men who have sex with men in Shanghai, China. Two CRF01_AE subtype-infected participants (3.8%), a 50years old MB and a 24years old general MSM, harbored viruses with a M46L mutation conferring resistance to protease inhibitors (PI). 2015 Infection, genetics and evolution Abstract HIV M46L 123 127 PR;PI 162;183 170;185 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. CONCLUSION: The frequency of the TDF induced K65R mutation was higher in our setting compared to non-subtype C dominated countries. 2015 PloS one Abstract HIV K65R 45 49 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. RESULTS: Compared to d4T-exposed patients (n = 7), patients failing on a TDF-containing regimen (n = 43) were almost 5 times more likely to present with a K65R mutation (aRR 4.86 95% CI 2.29 - 10.34). 2015 PloS one Abstract HIV K65R 155 159 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Virus from 9 of the 11 patients (82.0%) who developed the Y115F mutation also developed K65R. 2015 PloS one Abstract HIV K65R;Y115F 88;58 92;63 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Y115F was absent in the d4T group, and detected in 13.8% (n = 11) of TDF-exposed patients, p = 0.0007. 2015 PloS one Abstract HIV Y115F 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. N348I may interfere with the initiation of (+)-strand DNA synthesis by reducing polypurine tract (PPT) removal in the presence of nevirapine. 2015 Nucleic acids research Abstract HIV N348I 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The effect of NNRTIs on the RNase H-mediated cleavage of PPT-containing template-primers has been studied with wild-type HIV-1 RT and mutants N348I, T369I, T369V, T376S and N348I/T369I. 2015 Nucleic acids research Abstract HIV N348I;N348I;T369I;T369I;T369V;T376S 142;173;179;149;156;163 147;178;184;154;161;168 NNRTI;RT 14;127 20;129 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The enhancing effects of nevirapine and efavirenz were reduced in RTs carrying mutation N348I, and specially N348I/T369I. 2015 Nucleic acids research Abstract HIV N348I;N348I;T369I 88;109;115 93;114;120 RT 66 69 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The N348I/T369I RT showed reduced ability to generate short RNA products revealing a cleavage window defect. 2015 Nucleic acids research Abstract HIV N348I;T369I 4;10 9;15 RT 16 18 25666155 Combination of the R263K and M184I/V resistance substitutions against dolutegravir and lamivudine decreases HIV replicative capacity. The presence of R263K and M184I/V in a single virus resulted in substantial further decreases in the viral replicative capacity compared to that in the presence of single substitutions alone. 2015 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V;R263K 26;26;16 33;33;21 25666155 Combination of the R263K and M184I/V resistance substitutions against dolutegravir and lamivudine decreases HIV replicative capacity. We investigated the effect of combining the dolutegravir-specific R263K integrase resistance substitution with either M184I or M184V, two reverse transcriptase drug resistance substitutions that are frequently detected in individuals failing therapeutic regimens containing either lamivudine or emtricitabine. 2015 Antimicrobial agents and chemotherapy Abstract HIV M184I;M184V;R263K 118;127;66 123;132;71 RT;IN 138;72 159;81 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. A major drug resistant mutation in RT gene, L74I (NRTI), and two such mutations, K101E and G190A (NNRTI), were observed in two ART naive patients, while M184V was detected in two ART treated patients. 2015 Viruses Abstract HIV G190A;K101E;L74I;M184V 91;81;44;153 96;86;48;158 NNRTI;NRTI;RT 98;50;35 103;54;37 25680310 Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses. The most common TC-DRM present in >=50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). 2015 Clinical microbiology and infection Abstract HIV D67E;D67M;D67N;K103N;L90M;M41L;T215F;T215V;T215Y 53;53;53;79;110;70;61;61;61 59;59;59;84;114;74;68;68;68 PR 116 124 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Yet with substrate coevolution, while the wild-type dynamic behavior is restored in both p1-p6 ((LP) (1'F)p1-p6D30N/N88D) and NC-p1 ((AP) (2) (V)NC-p1V82A) bound proteases, the dynamic behavior of the NC-p1 bound protease variants (NC-p1V82A and (AP) (2) (V)NC-p1V82A) rather resemble those of the proteases bound to the other substrates, which is consistent with experimental studies. 2015 Evolutionary applications Abstract HIV D30N;V82A;V82A;V82A;N88D 111;150;237;263;116 115;154;241;267;120 PR;PR;PR;NC;NC;NC;NC;NC;Gag;Gag 162;213;298;126;145;201;232;258;92;109 171;221;307;128;147;203;234;260;94;111 25691633 Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro. E138K and G140S, as secondary substitutions to Q148H, Q148K, or Q148R, were associated with partial recovery in viral infectivity and/or INSTI resistance. 2015 Antimicrobial agents and chemotherapy Abstract HIV G140S;Q148H;Q148K;Q148R;E138K 10;47;54;64;0 15;52;59;69;5 INSTI 137 142 25691633 Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro. In the E92Q, Y143C, Y143R, and N155H mutants, no secondary substitutions were associated with DTG. 2015 Antimicrobial agents and chemotherapy Abstract HIV E92Q;N155H;Y143C;Y143R 7;31;13;20 11;36;18;25 25691633 Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro. In the Q148H, Q148K, or Q148R mutants, G140S/Q148H, E138K/Q148K, E138K/Q148R, and G140S/Q148R secondary mutations were identified with each INSTI and showed high resistance to RAL or EVG but limited resistance to DTG. 2015 Antimicrobial agents and chemotherapy Abstract HIV E138K;E138K;G140S;G140S;Q148H;Q148H;Q148K;Q148K;Q148R;Q148R;Q148R 52;65;39;82;7;45;14;58;71;24;88 57;70;44;87;12;50;19;63;76;29;93 INSTI 140 145 25691633 Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro. One explanation for this high barrier to resistance is that no additional secondary substitution of E92Q, Y143C, Y143R, or N155H simultaneously increased the fold change in 50% effective concentration (EC50) to DTG and infectivity. 2015 Antimicrobial agents and chemotherapy Abstract HIV E92Q;N155H;Y143C;Y143R 100;123;106;113 104;128;111;118 25691633 Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro. We conducted an in vitro resistance selection study using wild-type HIV-1 and mutants with the E92Q, Y143C, Y143R, Q148H, Q148K, Q148R, and N155H substitutions to assess the DTG in vitro barrier to resistance. 2015 Antimicrobial agents and chemotherapy Abstract HIV E92Q;N155H;Q148H;Q148K;Q148R;Y143C;Y143R 95;140;115;122;129;101;108 99;145;120;127;134;106;113 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. As guided by structure-based and computational studies, removal of the 5-Cl substitution of compound 1 on the catechol aryl ring system led to a new analogue compound 2 that maintains greater potency against Y181C and K103N/Y181C variants and better solubility (510 mug/mL). 2015 Journal of medicinal chemistry Abstract HIV K103N;Y181C;Y181C 218;208;224 223;213;229 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Comparison of the structures reveals that the Y181C mutation destabilizes the binding mode of compound 1 and disrupts the interactions with residues in the pocket. 2015 Journal of medicinal chemistry Abstract HIV Y181C 46 51 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Crystal structures were determined for wild-type, Y181C, and K103N/Y181C RT in complex with both compounds 1 and 2 to understand the structural basis for these findings. 2015 Journal of medicinal chemistry Abstract HIV K103N;Y181C;Y181C 61;67;50 66;72;55 RT 73 75 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Earlier analogues of the catechol diether compound series have picomolar activity against HIV strains with wild-type RT but lose potency against variants with single Y181C and double K103N/Y181C mutations. 2015 Journal of medicinal chemistry Abstract HIV K103N;Y181C;Y181C 183;189;166 188;194;171 RT 117 119 25704090 HIV-1 Vpr suppresses the cytomegalovirus promoter in a CRL4(DCAF1) E3 ligase independent manner. Interestingly, the Vpr mutant A30S/V31S protein also impaired the ability of Vpr to down-regulate transcription of the host UNG2 gene. 2015 Biochemical and biophysical research communications Abstract HIV A30S;V31S 30;35 34;39 Vpr;Vpr 19;77 22;80 25704446 Predicted residual activity of rilpivirine in HIV-1 infected patients failing therapy including NNRTIs efavirenz or nevirapine. Most prevalent RPV-RAMs after nevirapine experience were Y181C and H221Y, whereas L100I+K103N, Y188L and K101E occurred most in efavirenz-experienced patients. 2015 Clinical microbiology and infection Abstract HIV H221Y;K101E;K103N;L100I;Y181C;Y188L 67;105;88;82;57;95 72;110;93;87;62;100 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease. 2015 HIV medicine Abstract HIV D67E;D67G;D67N;G190A;G190E;G190S;K103N;K103S;L90M;M41L;M46I;M46L;T215C;T215D;T215E;T215F;T215I;T215N;T215S;T215V;T215Y 52;52;52;110;110;110;97;97;161;46;150;150;62;62;62;62;62;62;62;62;62 60;60;60;119;119;119;104;104;165;50;156;156;83;83;83;83;83;83;83;83;83 RT;PR 123;169 144;177 25712318 HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 78;64;64;64;148;148;148 83;73;73;73;157;157;157 25712318 HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia. At viraemia <=500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. 2015 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 43;29;29;29;91;91;91 48;38;38;38;100;100;100 25728072 Dolutegravir for the treatment of HIV-2 infection. Six out of 8 failing on raltegravir selected for integrase resistance mutations N155H (4), Y143G (1) and Q148R (1). 2015 Journal of clinical virology Abstract HIV N155H;Q148R;Y143G 80;105;91 85;110;96 IN 49 58 25728072 Dolutegravir for the treatment of HIV-2 infection. Two patients bearing N155H subsequently received dolutegravir. 2015 Journal of clinical virology Abstract HIV N155H 21 26 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Gag mutations I147X in the ISW9 epitope were seen in 43%: (10/23) clade A compared to 5%: (1/21) clade D infected subjects, p=0.007, Fisher's Exact test. 2015 Vaccine Abstract HIV I147X 14 19 Gag 0 3 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. RESULTS: Overall, Gag escape mutations A163X in KF11 were detected in 61% (14/23) A1- infected compared to 5% (1/21) in D-infected subjects (p=0.00015). 2015 Vaccine Abstract HIV A163X 39 44 Gag 18 21 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. CONCLUSIONS: The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N197D 147 152 gp120 165 170 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N197D;N463Q 127;76 132;81 gp120 102 107 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. RESULTS: Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N197D;N301Q 91;97 96;102 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. Analysis of reverse transcriptase revealed M184V (88%), K103N/S (32%), and Y181C/I/V (41%) DRMs, with the latter conferring reduced susceptibility to the salvage therapy candidates etravirine and rilpivirine. 2015 Journal of medical virology Abstract HIV K103N;K103S;M184V;Y181C;Y181I;Y181V 56;56;43;75;75;75 63;63;48;84;84;84 RT 12 33 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. Three patients (5%) had major protease inhibitor (PI) resistance mutations: all three had the V82A mutation, and one patient (Clade J virus) had a concurrent M46I, Q58E, and L76V DRM. 2015 Journal of medical virology Abstract HIV L76V;M46I;Q58E;V82A 174;158;164;94 178;162;168;98 PR;PI 30;50 38;52 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Introduction of either K65K or K66K into HIV-1 containing D67N/K70R reversed the error-prone DNA synthesis at codons 65-67 in RT and improved viral replication fitness, but did not impact RT inhibitor drug susceptibility. 2015 Nucleic acids research Abstract HIV D67N;K65K;K66K;K70R 58;23;31;63 62;27;35;67 RT;RT 126;188 128;190 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. These silent K65K and K66K mutations in the HIV-1 reverse transcriptase (RT) occur in over 35% of drug-experienced individuals and are highly associated with the thymidine analog mutations D67N and K70R, which confer decreased susceptibility to most nucleoside and nucleotide RT inhibitors. 2015 Nucleic acids research Abstract HIV D67N;K65K;K66K;K70R 189;13;22;198 193;17;26;202 RT;RT;RT 50;73;276 71;75;278 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Using Illumina next-generation sequencing, we demonstrate that the D67N/K70R substitutions in HIV-1 RT increase indel frequency by 100-fold at RT codons 65-67, consequently impairing viral fitness. 2015 Nucleic acids research Abstract HIV D67N;K70R 67;72 71;76 RT;RT 100;143 102;145 25769019 Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment. Among the 17 women with quantifiable viral load, median HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). 2015 AIDS research and human retroviruses Abstract HIV M184V 144 149 25777786 Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. 2015 Journal of medical virology Abstract HIV K103N;K219E;K219N;K219Q;K219R;L90M 91;63;63;63;63;117 96;71;71;71;71;121 NNRTI;NRTI;PI 109;84;134 115;89;137 25779585 Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. Although the K65R substitution is more common in subtype C viruses, the impact of subtype variability on NcRTI susceptibility has not been studied. 2015 Antimicrobial agents and chemotherapy Abstract HIV K65R 13 17 25779585 Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. Compound A is a novel nucleotide-competing HIV-1 reverse transcriptase (RT) inhibitor (NcRTI) that selects for a unique W153L substitution that confers hypersusceptibility to tenofovir, while the K65R substitution in RT confers resistance against tenofovir and enhances susceptibility to NcRTIs. 2015 Antimicrobial agents and chemotherapy Abstract HIV K65R;W153L 196;120 200;125 RT;RT;RT 49;72;217 70;74;219 25779585 Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. Steady-state kinetic analysis showed that K65R RTs enhanced the susceptibility to compound A by increasing binding of the inhibitor to the nucleotide binding site of RT in a subtype-independent manner, without significantly discriminating against the natural nucleotide substrate. 2015 Antimicrobial agents and chemotherapy Abstract HIV K65R 42 46 RT;RT 47;166 50;168 25779585 Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. These data highlight the potential utility of NcRTIs, such as compound A, for treatment of infections with K65R substitution-containing viruses, regardless of HIV-1 subtype. 2015 Antimicrobial agents and chemotherapy Abstract HIV K65R 107 111 25779585 Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. We confirmed the hypersusceptibility of K65R substitution-containing RTs to compound A for subtype C, CRF_A/G, and subtype B. 2015 Antimicrobial agents and chemotherapy Abstract HIV K65R 40 44 RT 69 72 25787278 Mechanism of HIV-1 Resistance to Short-Peptide Fusion Inhibitors Targeting the Gp41 Pocket. Two substitutions, E49K and N126K, located, respectively, at the N- and C-heptad repeat regions of gp41, were identified as conferring high resistance to the inhibitors targeting the pocket and cross-resistance to enfuvirtide (T20) and sifuvirtide (SFT). 2015 Journal of virology Abstract HIV E49K;N126K 19;28 23;33 gp41 99 103 25788547 Use of amplification refractory mutation system PCR assay as a simple and effective tool to detect HIV-1 drug resistance mutations. ARMS-PCR's limits of detection for mutations M184V, T215Y/F, K103N, and Y181C were <75 copies/ml, 143 copies/ml, 143 copies/ml, and 836 copies/ml, respectively. 2015 Journal of clinical microbiology Abstract HIV K103N;M184V;T215F;T215Y;Y181C 61;45;52;52;72 66;50;59;59;77 25788547 Use of amplification refractory mutation system PCR assay as a simple and effective tool to detect HIV-1 drug resistance mutations. The ARMS-PCR assay was able to detect M184V, T215Y/F, K103N, and Y181C mutations with sensitivities of 96.8%, 85.7%, 91.3%, and 70%, respectively, and specificities of 90.6%, 95%, 100%, 96.9%, respectively, compared with data on sequencing. 2015 Journal of clinical microbiology Abstract HIV K103N;M184V;T215F;T215Y;Y181C 54;38;45;45;65 59;43;52;52;70 25788547 Use of amplification refractory mutation system PCR assay as a simple and effective tool to detect HIV-1 drug resistance mutations. The results indicated the highest positive predictive value for K103N (100%) and the highest negative predictive value for M184V (97.5%). 2015 Journal of clinical microbiology Abstract HIV K103N;M184V 64;123 69;128 25803373 HIV-1 Antiretroviral Drug Resistance in Pregnant Women in Jamaica: A Preliminary Report. Three minor protease resistant-conferring mutations (A71AT, A71V, A71T) and five mutations conferring high to low-level resistance (K219EK, T69S, K103S, G190A and K103N) were detected in the RT region. 2014 The West Indian medical journal Abstract HIV A71A;A71T;A71T;A71V;G190A;K103N;K103S;K219E;K219K;T69S 53;53;66;60;153;163;146;132;132;140 58;58;70;64;158;168;151;138;138;144 PR;RT 12;191 20;193 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. In contrast, HIV-1NL4-3 mutants E92Q + N155H, G140S + Q148R, and T97A + Y143C showed 2-fold, 4-fold, and no increase in EC50, respectively, relative to the parental strain. 2015 Retrovirology Abstract HIV E92Q;G140S;N155H;Q148R;T97A;Y143C 32;46;39;54;65;72 36;51;44;59;69;77 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Integrase substitutions E92Q, Y143C, E92Q + Y143C, and Q148R conferred relatively low levels of resistance to dolutegravir in HIV-2ROD9 (2- to 6-fold), but Q148K, E92Q + N155H, T97A + N155H and G140S + Q148R resulted in moderate resistance (10- to 46-fold), and the combination of T97A + Y143C in HIV-2ROD9 conferred high-level resistance (>5000-fold). 2015 Retrovirology Abstract HIV E92Q;E92Q;E92Q;G140S;N155H;N155H;Q148K;Q148R;Q148R;T97A;T97A;Y143C;Y143C;Y143C 24;37;163;194;170;184;156;55;202;177;281;30;44;288 28;41;167;199;175;189;161;60;207;181;285;35;49;293 IN 0 9 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. The resistance phenotypes for E92Q + N155H, and G140S + Q148R HIV-2ROD9 were also confirmed in spreading infections of CEM-ss cells. 2015 Retrovirology Abstract HIV E92Q;G140S;N155H;Q148R 30;48;37;56 34;53;42;61 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Although K211I alone showed no AZTMP excision activity, excision efficiency doubled when K211I was present in combination with S345T and E350K. 2015 Retrovirology Abstract HIV E350K;K211I;K211I;S345T 137;9;89;127 142;14;94;132 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Four substitutions in the protease-reverse transcriptase (PR-RT) protein (K211I, I224T, S345T, E350K) are necessary to obtain highly AZT resistant and fully replication competent virus. 2015 Retrovirology Abstract HIV E350K;I224T;K211I;S345T 95;81;74;88 100;86;79;93 RT;PR;PR;RT 35;26;58;61 56;34;60;63 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. I224T is a polymorphism which is not essential for AZT resistance per se, but is important for regaining efficient replication of the resistant virus. 2015 Retrovirology Abstract HIV I224T 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Instead, S345T is responsible for creating an ATP binding site, probably by making an already existing tryptophan more accessible, which in turn can interact with ATP. 2015 Retrovirology Abstract HIV S345T 9 14 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. K211I also decreased nucleotide binding affinity and increased fidelity. 2015 Retrovirology Abstract HIV K211I 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. S345T is the only single substitution variant exhibiting significant AZTMP excision activity. 2015 Retrovirology Abstract HIV S345T 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. We could show by NMR spectroscopy that S345T is responsible for ATP binding, probably by making a tryptophan residue accessible. 2015 Retrovirology Abstract HIV S345T 39 44 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. A dominant R71K mutation in the Nef71-79 occurred in those with HLA-B*07:02 but not B*42:01/02 or B*81:01. 2015 Retrovirology Abstract HIV R71K 11 15 Nef 32 35 25826000 Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam. Y181C, a nevirapine resistance mutation, appeared in two (25%) children 1 and 3 months after birth, respectively. 2015 AIDS research and human retroviruses Abstract HIV Y181C 0 5 25845390 HIV Type 1 Subtype A1 Dominates in Armenia. The prevalence of drug resistance in naive patients was low (1.5%) with the only one mutation K219Q found. 2015 Current HIV research Abstract HIV K219Q 94 99 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Four NNRTI SDRMs:K101E, K103N, Y181C, and G190A:accounted for >80% of NNRTI-associated TDR in all regions and subtypes. 2015 PLoS medicine Abstract HIV G190A;K101E;K103N;Y181C 42;17;24;31 47;22;29;36 NNRTI;NNRTI 5;70 10;75 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. An isoleucine-to-proline change (I559P) in the gp41 ectodomain has been used to stabilize soluble forms of HIV-1 Env trimers for structural characterization and for use as immunogens. 2015 PloS one Abstract HIV I559P 33 38 gp41;Env 47;113 51;116 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Compared with the wild-type Env, the I559P Env was recognized inefficiently by polyclonal sera from HIV-1-infected individuals, by several gp41-directed antibodies, by some antibodies against the CD4-binding site of gp120, and by antibodies that preferentially recognize the CD4-bound Env. 2015 PloS one Abstract HIV I559P 37 42 gp41;gp120;Env;Env;Env 139;216;28;43;285 143;221;31;46;288 HIV infections 100 114 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. In the native membrane-anchored HIV-1BG505 Env, the I559P change modestly decreased proteolytic maturation, increased the non-covalent association of gp120 with the Env trimer, and resulted in an Env conformation distinctly different from that of the wild-type HIV-1BG505 Env. 2015 PloS one Abstract HIV I559P 52 57 gp120;Env;Env;Env;Env 150;43;165;196;272 155;46;168;199;275 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Some of the gp120-associated antigenic differences between the wild-type HIV-1BG505 Env and the I559P mutant were compensated by the SOS disulfide bond between gp120 and gp41, which has been used to stabilize cleaved soluble Env trimers. 2015 PloS one Abstract HIV I559P 96 101 gp120;gp120;gp41;Env;Env 12;160;170;84;225 17;165;174;87;228 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P change completely eliminated the ability of the HIV-1BG505 Env to mediate cell-cell fusion and virus entry, and abolished the capacity of the SOS Env to support virus infection in the presence of a reducing agent. 2015 PloS one Abstract HIV I559P 4 9 Env;Env 69;156 72;159 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. These results suggest that differences exist between the quaternary structures of functional Env spikes and I559P Envs. 2015 PloS one Abstract HIV I559P 108 113 Env;Env 93;114 96;118 25858608 [Resistance profile and genetic barrier of dolutegravir]. Dolutegravir displays in vitro activity against mutant HIV-1 harboring any isolated resistance mutations selected during failures to raltegravir or elvitegravir (Y143C/H/, N155H, Q148H/K/R, E92G/Q, T66A/I/K, T97A, E138A/K, G140A/S). 2015 Enfermedades infecciosas y microbiologia clinica Abstract HIV E138A;E138K;E92G;E92Q;G140A;G140S;N155H;Q148H;Q148K;Q148R;T66A;T66I;T66K;T97A;Y143C;Y143H 214;214;190;190;223;223;172;179;179;179;198;198;198;208;162;162 221;221;196;196;230;230;177;188;188;188;206;206;206;212;169;169 25858608 [Resistance profile and genetic barrier of dolutegravir]. In multitreated patients with widespread resistance including IN resistance, the high efficacy of dolutegravir was confirmed, irrespective of the previous pattern of IN mutations, provided that Q148X associated with other mutations was absent. 2015 Enfermedades infecciosas y microbiologia clinica Abstract HIV Q148X 194 199 IN;IN 62;166 64;168 25858608 [Resistance profile and genetic barrier of dolutegravir]. Its activity is only compromised by Q148X mutations combined with other mutations, particularly > 1 mutation. 2015 Enfermedades infecciosas y microbiologia clinica Abstract HIV Q148X 36 41 25858608 [Resistance profile and genetic barrier of dolutegravir]. The mutations eventually selected (R263K, H51Y and E138K) do not confer significant resistance, and induce a fitness cost that prevents HIV-1 from evading drug pressure. 2015 Enfermedades infecciosas y microbiologia clinica Abstract HIV E138K;H51Y;R263K 51;42;35 56;46;40 25860884 SiRNA-induced mutation in HIV-1 polypurine tract region and its influence on viral fitness. In contrast, introducing the T(-16)A or both mutations into the cPPT rendered the virus(es) incapable of replication, most likely due to the F185L integrase mutation produced by this nucleotide substitution. 2015 PloS one Abstract HIV F185L 141 146 IN 147 156 25876868 [HIV-1 subtype diversity and transmission clusters among men having sex with men who recently got HIV-l infection, in Zhejiang province]. Three surveillance drug resistance mutations (M46I, T215S and G190A) were found in three samples (each sample harbored only one resistance mutation). 2015 Zhonghua liu xing bing xue za zhi Abstract HIV G190A;M46I;T215S 62;46;52 67;50;57 25879488 Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011. RESULTS: Our results show that THDR has been at low level from 2009 to 2011, only K101E and V179D mutation was detected which did not belong to the major HIV-1 drug resistance mutations. 2015 BMC public health Abstract HIV K101E;V179D 82;92 87;97 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. Frequency of K101E was also significantly higher in subtype A (36.5% vs. 2015 Georgian medical news Abstract HIV K101E 13 18 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. Frequent co-occurrence of G190S with Y181C and K101E may limit the use of novel generation NNRTIs in subtype A infected patients with previous exposure to this drug class. 2015 Georgian medical news Abstract HIV G190S;K101E;Y181C 26;47;37 31;52;42 NNRTI 91 97 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. High prevalence of G190S and K101 mutations suggests subtype A specific response to currently approved first-line NNRTIs. 2015 Georgian medical news Abstract HIV G190S 19 24 NNRTI 114 120 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. In 69 samples G190S co-occurred with either K101E or Y181C or with both: 39 genotypes G190S/K101E; 10 genotypes G190S/Y181CI and 20 genotypes G190S/K101E/Y181CI. 2015 Georgian medical news Abstract HIV G190S;K101E;Y181C;Y181I;G190S;G190S;G190S;K101E;K101E;Y181C;Y181C;Y181I 142;148;154;154;14;86;112;44;92;118;53;118 147;153;159;160;19;91;117;49;97;123;58;124 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. Other significant NNRTI mutations included K101E (31.6%, n=61), K103N (30.1%, n=58) and Y181CI (26.9%, n=52). 2015 Georgian medical news Abstract HIV K101E;K103N;Y181C;Y181I 43;64;88;88 48;69;94;94 NNRTI 18 23 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. The most common nucleoside reverse transcriptase inhibitor (NRTI) mutation was M184V - 86.0% (n=166). 2015 Georgian medical news Abstract HIV M184V 79 84 NRTI;NRTI 16;60 48;64 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation was G190S, found in 105 (54.4%) of samples. 2015 Georgian medical news Abstract HIV G190S 86 91 NNRTI;NNRTI 18;66 54;71 25879553 Distinct drug resistance profile of HIV-1 subtype A strain circulating in Georgia. The prevalence of G190S was 62.3% in subtype A viruses compared to 3.8% in non-A variants (p<0.0001). 2015 Georgian medical news Abstract HIV G190S 18 23 25885327 HIV-1 subtype B-infected MSM may have driven the spread of transmitted resistant strains in France in 2007-12: impact on susceptibility to first-line strategies. Additionally, 5/331 strains isolated in 2010-12 had integrase inhibitor (II)-related RAMs (isolated E157Q mutation in all cases). 2015 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 100 105 IN 52 61 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. In contrast, the replication-impaired K65R virus did not induce detectable T-cell responses, likely reflecting the need for adequate replication. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 38 42 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. METHODS: Thirty-six female pigtail macaques received up to 20 repeat low-dose vaginal inoculations with wild-type (WT) SHIVSF162P3 (n = 24) or a clonal derivative with the tenofovir (TFV) K65R drug-resistant mutation (n = 12). 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 186 192 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. PrEP consisted of oral Truvada (n = 6, WT), TFV vaginal gel (n = 6, K65R), or TFV intravaginal ring (n = 6, WT). 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 68 72 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. The remaining animals were PrEP-inexperienced controls (n = 12, WT; n = 6, K65R). 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 75 79 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. The most common mutation was K103N, which confers high-level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). 2015 Virology journal Abstract HIV K103N 29 34 NNRTI;NNRTI 75;124 111;129 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. Antiretroviral drug resistance mutations K103N and E138A were also detected, indicating possible transmission of anti-retroviral drug resistance mutations. 2015 Virology journal Abstract HIV E138A;K103N 51;41 56;46 25892414 Prediction of drug-resistance using genotypic and docking analysis among anti-retroviral therapy naive and first-line treatment failures in Salem, Tamil Nadu, India. The mutations of I135R/T/V/X, L178 I/M, M184V/I, D67N, K70R, and K103N were the most common among these 23 patients. 2015 Current HIV research Abstract HIV D67N;I135R;I135T;I135V;I135X;K103N;K70R;L178I;L178M;M184I;M184V 49;17;17;17;17;65;55;30;30;40;40 53;28;28;28;28;70;59;38;38;47;47 25919760 Genetic Changes in HIV-1 Gag-Protease Associated with Protease Inhibitor-Based Therapy Failure in Pediatric Patients. Major protease resistance mutations (M46I, I54V, and V82A) were identified in eight (40%) patients, as well as Gag cleavage site (CS) mutations (at codons 373, 374, 378, 428, 431, 449, 451, and 453) in nine (45%) patients. 2015 AIDS research and human retroviruses Abstract HIV I54V;M46I;V82A 43;37;53 47;41;57 PR;Gag 6;111 14;114 25919896 Genetic Diversity and Drug Resistance Among Antiretroviral Treatment-Failed Individuals from 2010 to 2012 in Honghe, China. Mutations such as M184V, A62V, T69Ins, K103N, Y181C, and G190A were common among the ART-failed individuals. 2015 AIDS research and human retroviruses Abstract HIV A62V;G190A;K103N;M184V;Y181C 25;57;39;18;46 29;62;44;23;51 25919896 Genetic Diversity and Drug Resistance Among Antiretroviral Treatment-Failed Individuals from 2010 to 2012 in Honghe, China. The frequencies of M184V, A62V, and K103N were 20.5%, 11.0%, and 23.6%, respectively. 2015 AIDS research and human retroviruses Abstract HIV A62V;K103N;M184V 26;36;19 30;41;24 25920233 Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors. Although K156A conferred resistance to diketo acid-branched bis-catechol hybrid inhibitors, neither K156A nor K159A conferred resistance to their monocatechol counterparts, suggesting that bis-catechol moieties direct DCTAs toward K156. 2015 Natural product communications Abstract HIV K156A;K156A;K159A 9;100;110 14;105;115 25920233 Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors. IN K156N, a reported polymorphism associated with resistance to RGV, conferred resistance to L-CA and STI as well. 2015 Natural product communications Abstract HIV K156N 3 8 IN;Capsid 0;95 2;97 25920233 Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors. To investigate the apparent preference L-CA exhibits for interactions with K156, we assayed the potency of several hybrid inhibitors containing combinations of DCTA and STI pharmacophores against recombinant IN K156A or K159A. 2015 Natural product communications Abstract HIV K156A;K159A 211;220 216;225 IN;Capsid 208;41 210;43 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. In one child, the majority species contained M184V in reverse transcriptase linked to L10F, M46I/L, I54V, and V82A in PR and a triple-class drug-resistant variant with these mutations linked to the NNRTI mutation V108I. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV I54V;L10F;M184V;M46I;M46L;V108I;V82A 100;86;45;92;92;213;110 104;90;50;98;98;218;114 RT;NNRTI;PR 54;198;118 75;203;120 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. In the second child, the majority species contained M184V and V82A linked within viral genomes. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;V82A 52;62 57;66 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. CONCLUSION: In some patients, first-line ART had the possibility to provide sufficient treatment effect for over than 72 months, but in long-term treatment, the dominant NNRTI drug resistance mutation K103N could reduced, while the proportion of variants with mutation Y181C or G190A may increased. 2014 AIDS research and therapy Abstract HIV G190A;K103N;Y181C 278;201;269 283;206;274 NNRTI 170 175 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In the sequences of standard genotype HIV drug resistance assay, the frequency of K103N, Y181C and G190A had the similar pattern with that in SGA sequences. 2014 AIDS research and therapy Abstract HIV G190A;K103N;Y181C 99;82;89 104;87;94 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In this assay, we focused on the development of primary drug resistance mutations against Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), K103N, Y181C and G190A. 2014 AIDS research and therapy Abstract HIV G190A;K103N;Y181C 163;146;153 168;151;158 NNRTI;NNRTI 90;138 126;143 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. RESULT: In the SGA sequences, the K103N decreased and vanished, while the frequency of Y181C and G190A increased in individual patient receiving long-term Antiretroviral Therapy (ART). 2014 AIDS research and therapy Abstract HIV G190A;K103N;Y181C 97;34;87 102;39;92 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. This result was not similar with that in vitro study, which state that variant with K103N or Y181C had an equal viral fitness with wild type. 2014 AIDS research and therapy Abstract HIV K103N;Y181C 84;93 89;98 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. We used Single Genome Amplification (SGA) to analyze the frequency of K103N, Y181C and G190A in serial plasma samples of three individual patients. 2014 AIDS research and therapy Abstract HIV G190A;K103N;Y181C 87;70;77 92;75;82 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. Of 15/313 patients who met the criteria for resistance analysis, one developed a darunavir RAM as a mixture with wild-type (I84I/V), without phenotypic resistance to darunavir. 2014 AIDS research and therapy Abstract HIV I84I;I84V 124;124 130;130 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Comparison of the mutants resistance to the known strand transfer inhibitors raltegravir and elvitegravir, and a new inhibitor XZ-259 (a dihydro-1H-isoindol derivative), showed that integrases of both subtypes with the Q148K mutation were insensitive to raltegravir and elvitegravir but were effectively inhibited by XZ-259. 2015 Acta naturae Abstract HIV Q148K 219 224 IN 182 192 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Its negative effect was partially compensated by the secondary mutations E138K and G140S. 2015 Acta naturae Abstract HIV E138K;G140S 73;83 78;88 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Primary substitution G118R had different influence on the activity of proteins of the subtypes A and B, and the compensatory effect of the secondary substitution E138K also depended on the viral subtype. 2015 Acta naturae Abstract HIV E138K;G118R 162;21 167;26 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The mutation Q148K almost equally reduced the activity of integrases of both subtypes. 2015 Acta naturae Abstract HIV Q148K 13 18 IN 58 68 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The substitution G118R slightly reduced the efficiency of IN inhibition by raltegravir and elvitegravir and caused no resistance to XZ_259. 2015 Acta naturae Abstract HIV G118R 17 22 IN 58 60 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. To assess the impact of drug resistance mutations on the activity of IN of HIV-1 subtype A strain FSU-A, which is dominant in Russia, variants of the consensus IN of this subtype containing the primary resistance mutations G118R and Q148K and secondary compensatory substitutions E138K and G140S were prepared and characterized. 2015 Acta naturae Abstract HIV E138K;G118R;G140S;Q148K 280;223;290;233 285;228;295;238 IN;IN 69;160 71;162 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. Most subjects selected the K103N mutation (22% (10/45) of all patients and 66% (10/15) of those with high-level NVP resistance). 2015 Journal of medical virology Abstract HIV K103N 27 32 25956162 Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. Analysis of two cases of virological failure during raltegravir-based therapy showed that the accumulation and the rapid evolution of primary INSTI resistance-associated mutations coincided with the S119R mutation. 2015 Antiviral research Abstract HIV S119R 199 204 INSTI 142 147 25956162 Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. In the present study, we focused on the S119G/R/P/T (S119X) polymorphisms, which are frequently observed in HIV-1 sequences derived from clinical specimens (naive, n=458, 26%). 2015 Antiviral research Abstract HIV S119G;S119P;S119R;S119T;S119X 40;40;40;40;53 51;51;51;51;58 25956162 Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. Notably, the S119R polymorphism contributed to a significant (5.9-fold) increase in dolutegravir resistance caused by G140S/Q148H. 2015 Antiviral research Abstract HIV G140S;Q148H;S119R 118;124;13 123;129;18 25956162 Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. Our in vitro assays revealed that S119G/P/T alone exerted no effect on the susceptibility to INSTIs, whereas S119R enhanced the level of INSTI resistance induced by well-known INSTI resistance-associated mutations (Y143C, Q148H or N155H). 2015 Antiviral research Abstract HIV N155H;Q148H;S119G;S119P;S119R;S119T;Y143C 231;222;34;34;109;34;215 236;227;43;43;114;43;220 INSTI;INSTI;INSTI 93;137;176 99;142;181 25956162 Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. The frequency of the S119X polymorphism together with Q148H/R (n=8, 63%) or N155H (n=12, 83%) was relatively high compared with that of naive group. 2015 Antiviral research Abstract HIV N155H;Q148H;Q148R;S119X 76;54;54;21 81;61;61;26 25956162 Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance. These data highlight the role of the S119X polymorphism in INSTI resistance, and this polymorphism might be linked to the potential treatment outcome with INSTI-based therapy. 2015 Antiviral research Abstract HIV S119X 37 42 INSTI;INSTI 59;155 64;160 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. Although not in the WHO SDRMs list, several minor protease inhibitor resistant mutations listed in the International Antiviral Society-USA panel were identified, of which M36I, H69K, L89M/V/I (each one 100%) and K20R/T (92.5%) can be considered as polymorphic signatures for CRF35_AD.The relatively high rate of TDR mutations in our study raises concerns about the risk of treatment failure in chronically infected IDUs of Sanandaj city. 2015 PloS one Abstract HIV H69K;K20R;K20T;L89I;L89M;L89V;M36I 177;212;212;183;183;183;171 181;218;218;191;191;191;175 PR 50 58 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. The frequency of SDRMs to any class of antiretroviral drugs was 15%, which included mutations to nucleoside reverse transcriptase inhibitors (NRTIs, 10%), with M41L and M184V as the most common (5%), and non-nucleoside reverse transcriptase inhibitors (NNRTIs, 5%), with K103N as the only detected mutation (5%). 2015 PloS one Abstract HIV K103N;M184V;M41L 271;169;160 276;174;164 NNRTI;NRTI;NNRTI;NRTI 204;97;253;142 240;129;259;147 25970090 Change in the Prevalence of HIV-1 and the Rate of Transmitted Drug-Resistant HIV-1 in Haiphong, Northern Vietnam. Nonnucleoside RT inhibitor-resistant mutations, Y181C/I, were detected in three subjects; one had the nucleoside RT inhibitor-resistant mutations L74V and M184V and one had E138K. 2015 AIDS research and human retroviruses Abstract HIV E138K;L74V;M184V;Y181C;Y181I 173;146;155;48;48 178;150;160;55;55 RT;RT 14;113 16;115 25972553 Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A/E Infections. RT181 mutations affected CTL recognition in both subtype A/E and B infections, while the RT Y181C mutation has been accumulating in treatment-naive Vietnamese. 2015 Journal of virology Abstract HIV Y181C 92 97 RT;RT 0;89 2;91 25972553 Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A/E Infections. The results suggest that the Y181C mutation may influence HIV-1 control by CTLs in Vietnam. 2015 Journal of virology Abstract HIV Y181C 29 34 25972553 Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A/E Infections. The Y181C mutation may influence HIV-1 control by the CTLs in Vietnam, since this mutation has been accumulating in treatment-naive Vietnamese. 2015 Journal of virology Abstract HIV Y181C 4 9 25972553 Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A/E Infections. The Y181C mutation was found to be accumulating in treatment-naive Vietnamese infected with the subtype A/E virus. 2015 Journal of virology Abstract HIV Y181C 4 9 25972553 Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A/E Infections. We investigated the effect of nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI)-resistance mutations (Y181C, Y181I, and Y181V) on epitope recognition by CTLs specific for 3 different HIV-1 epitopes (HLA-A*02:01-restricted IV10, HLA-B*35:01-restricted NY9, and HLA-C*12:02-restricted KY9) in subtype B and subtype A/E infections and the accumulation of these mutations in treatment-naive Japanese and Vietnamese. 2015 Journal of virology Abstract HIV Y181C;Y181I;Y181V 111;118;129 116;123;134 NNRTI;NNRTI;RT 30;82;67 65;87;69 25976289 Phylogenetic analysis of HIV-1 subtypes and drug resistance profile among treatment-naive people in Kuwait. A62V and A98G were non-polymorphic resistance-associated mutations (RAMs) detected in the RT region of two and three patients, respectively. 2015 Journal of medical virology Abstract HIV A98G;A62V 9;0 13;4 RT 90 92 25991470 Evidence of Self-Sustaining Drug Resistant HIV-1 Lineages Among Untreated Patients in the United Kingdom. METHODS: We extracted all subtype B HIV-1 pol gene sequences from treatment-naive patients within the United Kingdom HIV Drug Resistance Database sampled between 1997 and 2011 and carrying the most common protease inhibitors, nonnucleoside and nucleotide reverse transcriptase inhibitors TDR mutations, namely, L90M, K103N, and T215Y/F/rev, respectively (n = 1140). 2015 Clinical infectious diseases Abstract HIV K103N;L90M;T215F;T215Y 317;311;328;328 322;315;339;339 RT;PR;Pol;Rev 255;205;42;336 276;213;45;339 25991470 Evidence of Self-Sustaining Drug Resistant HIV-1 Lineages Among Untreated Patients in the United Kingdom. RESULTS: T215rev was present alone in 47% of the sequences (n = 540), K103N in 31% (n = 359), and L90M in 10% (n = 109). 2015 Clinical infectious diseases Abstract HIV K103N;L90M 70;98 75;102 25991470 Evidence of Self-Sustaining Drug Resistant HIV-1 Lineages Among Untreated Patients in the United Kingdom. The remaining sequences contained T215Y or combinations of L90M, K103N, and T215rev. 2015 Clinical infectious diseases Abstract HIV K103N;L90M;T215Y 65;59;34 70;63;39 25995261 A Novel Leu92 Mutant of HIV-1 Reverse Transcriptase with a Selective Deficiency in Strand Transfer Causes a Loss of Viral Replication. Furthermore, when the RT's L92P mutant was introduced into an infectious HIV-1 clone, it lost viral replication, due to inefficient intracellular strand transfers during RTN, thus supporting the in vitro data. 2015 Journal of virology Abstract HIV L92P 27 31 RT 22 24 25995261 A Novel Leu92 Mutant of HIV-1 Reverse Transcriptase with a Selective Deficiency in Strand Transfer Causes a Loss of Viral Replication. Nevertheless, we show here that a specific mutation in HIV-1 RT (L92P) that does not affect the DNA polymerase and RNase H activities abolishes strand transfer. 2015 Journal of virology Abstract HIV L92P 65 69 Pol;RT 100;61 110;63 25995261 A Novel Leu92 Mutant of HIV-1 Reverse Transcriptase with a Selective Deficiency in Strand Transfer Causes a Loss of Viral Replication. We show here for the first time that a single mutation in HIV-1 reverse transcriptase (L92P) selectively abolishes strand transfers without affecting the enzyme's DNA polymerase and RNase H functions. 2015 Journal of virology Abstract HIV L92P 87 91 RT;Pol 64;167 85;177 26003522 P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core. Substitution of positively or negatively charged residues in the distal region of 6-HB with alanines resulted in significant decrease or increase of its binding affinity to P20A, respectively. 2015 Microbes and infection Abstract HIV P20A 173 177 26003522 P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core. The 6-HB with E630K, D632K, or E634K mutation exhibited enhanced binding affinity with P20A, suggesting that P20A blocks HIV-1 fusion through electrostatic interaction with the positively charged residues in the distal region of the gp41 fusion core. 2015 Microbes and infection Abstract HIV D632K;E630K;E634K;P20A;P20A 21;14;31;87;109 26;19;36;91;113 gp41 233 237 26003522 P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core. Using alanine scanning mutagenesis, we investigated the effect of 6-HB surface residue mutations on the binding affinity between P20A and 6-HB. 2015 Microbes and infection Abstract HIV P20A 129 133 26003522 P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core. We previously identified an HIV-1 fusion inhibitor P20A targeting HIV-1 gp41 6-HB fusion core. 2015 Microbes and infection Abstract HIV P20A 51 55 gp41 72 76 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. T215D revertant mutation was transmitted in a large cluster comprising 25 individuals. 2015 PloS one Abstract HIV T215D 0 5 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. Molecular dynamics simulations are performed to investigate the dynamic properties of wild-type HIV-1 protease and its two multi-drug-resistant variants (Flap + (L10I/G48V/I54V/V82A) and Act (V82T/I84V)) as well as their binding with APV and DRV inhibitors. 2015 Scientific reports Abstract HIV L10I;G48V;I54V;V82A;V82T;I84V 162;167;172;177;192;197 166;171;176;181;196;201 PR 102 110 26016726 Characteristics and genotype profiles of antiretroviral-naive patients entering a Southern US HIV outpatient clinic 2009-2012. The antiretroviral class with the most common major mutation was the non-nucleoside reverse transcriptase inhibitors (NNRTIs) where K103N was the most common major NNRTI mutation at presentation. 2016 International journal of STD & AIDS Abstract HIV K103N 132 137 NNRTI;NNRTI;NNRTI 69;118;164 105;124;169 26017662 HIV-1 Group O Resistance Against Integrase Inhibitors. CONCLUSIONS: HIV-O harboring Q148R and N155H shows higher resistance to DTG compared with HIV-M subtype B. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N155H;Q148R 39;29 44;34 26017662 HIV-1 Group O Resistance Against Integrase Inhibitors. In the DTG selections, subtype B yielded S153Y, whereas a natural S153A polymorphism sometimes led to A153V in group O. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV A153V;S153A;S153Y 102;66;41 107;71;46 26017662 HIV-1 Group O Resistance Against Integrase Inhibitors. Site-directed mutagenesis was performed on the pCOM2.5 HIV group 0 infectious clone to ascertain the impact of INSTI resistance substitutions at positions Q148R, N155H, and R263K within integrase on susceptibility to INSTIs and infectiousness. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N155H;Q148R;R263K 162;155;173 167;160;178 IN;INSTI;INSTI 186;111;217 195;116;223 26017662 HIV-1 Group O Resistance Against Integrase Inhibitors. The pCMO2.5/Q148R and pCMO2.5/N155H variants displayed far higher levels of resistance to DTG (>1000 FC) than was seen for group M viruses. 2015 Journal of acquired immune deficiency syndromes (1999) Abstract HIV N155H;Q148R 30;12 35;17 26020400 Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. 2015 Medicine Abstract HIV M46I;Y181C 37;73 41;78 PR;RT 53;92 61;113 26021068 [Indicators of the human immunodeficiency virus drug resistance to antiretroviral drugs in HIV-infected individuals in the Siberian Federal District in 2010-2012]. Among the main drug resistance mutations for the entire period of observation was a high frequency of the occurrence M184V mutation, K101E, K103N, Y181C, and G190S influencing the development of the HIV resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors. 2015 Voprosy virusologii Abstract HIV G190S;K101E;K103N;M184V;Y181C 158;133;140;117;147 163;138;145;122;152 NNRTI 232 268 26038551 Identification of mechanistically distinct inhibitors of HIV-1 reverse transcriptase through fragment screening. The dNTP competing RT inhibitor retains activity against the NRTI-resistant mutants K65R and M184V, demonstrating a drug resistance profile distinct from the nucleotide competing RT inhibitors indolopyridone-1 (INDOPY-1) and 4-dimethylamino-6-vinylpyrimidine-1 (DAVP-1). 2015 Proc Natl Acad Sci U S A Abstract HIV K65R;M184V 84;93 88;98 NRTI;RT;RT 61;19;179 65;21;181 26038551 Identification of mechanistically distinct inhibitors of HIV-1 reverse transcriptase through fragment screening. Three compounds were found to inhibit RNA- and DNA-dependent DNA polymerase activity of HIV-1 RT in the micromolar range while retaining potency against RT variants carrying one of three major NNRTI resistance mutations: K103N, Y181C, or G190A. 2015 Proc Natl Acad Sci U S A Abstract HIV G190A;K103N;Y181C 238;221;228 243;226;233 Pol;NNRTI;RT;RT 65;193;94;153 75;198;96;155 26055365 The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes. In addition, WPR-6 showed excellent antiviral potency against the most prevalent NNRTI-resistant viruses containing the K103N and Y181C mutations. 2015 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 120;130 125;135 NNRTI 81 86 26055365 The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes. The results demonstrated that V106I and Y188L were the two dominant NNRTI-associated resistance mutations detected in the breakthrough viruses. 2015 Antimicrobial agents and chemotherapy Abstract HIV V106I;Y188L 30;40 35;45 NNRTI 68 73 26060058 Association between a naturally arising polymorphism within a functional region of HIV-1 Nef and disease progression in chronic HIV-1 infection. Moreover, introduction of a Met-20-to-Ile mutation in a laboratory strain SF2 Nef resulted in a modest, albeit not statistically significant, increase in HLA class I downregulation activity (p = 0.06). 2015 Archives of virology Abstract HIV M20I 28 41 Nef 78 81 26075306 Short Communication: In Vitro Accumulation of Drug Resistance Mutations in Chimeric Infectious Clones Containing Subtype B or C Reverse Transcriptase and Selected with Tenofovir or Didanosine. Both patterns, M184V+K65R and Q151M+K65R, have a significant impact on NRTI resistance. 2015 AIDS research and human retroviruses Abstract HIV K65R;K65R;M184V;Q151M 21;36;15;30 25;40;20;35 NRTI 71 75 26075306 Short Communication: In Vitro Accumulation of Drug Resistance Mutations in Chimeric Infectious Clones Containing Subtype B or C Reverse Transcriptase and Selected with Tenofovir or Didanosine. Other primary mutations (M184V and Q151M) were selected with ddI treatment in conjunction with K65R only in RTC' viruses. 2015 AIDS research and human retroviruses Abstract HIV K65R;M184V;Q151M 95;25;35 99;31;40 26075306 Short Communication: In Vitro Accumulation of Drug Resistance Mutations in Chimeric Infectious Clones Containing Subtype B or C Reverse Transcriptase and Selected with Tenofovir or Didanosine. The mutation K65R is selected more quickly in RTC' than in RTB' viruses with TDF and ddI, and additional mutations (positions 45, 62, and 68) were selected after K65R fixation. 2015 AIDS research and human retroviruses Abstract HIV K65R;K65R 13;162 17;166 26077516 The prevalence and determinants of drug-resistance-associated mutations in the HIV-1-infected MSM population of Henan Province in China. After antiretroviral therapy (ART), the frequencies of K103N, G190A, Y181C, and V106A mutations were highly elevated. 2015 Archives of virology Abstract HIV G190A;K103N;V106A;Y181C 62;55;80;69 67;60;85;74 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. Combined with the previously constructed infectious clone of HIV-1 CRF07_BC subtype with I132L and T139K/R mutations in RT region, mutated PNL4-3 infectious clones were transfected into 293T cells. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;T139K;T139R 89;99;99 94;106;106 RT 120 122 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. CONCLUSION: The novel drug resistance associated mutations I132L and T139K/R can reduce the drug sensitivity to NNRTIs in subtype B and CRF07_BC, and the replication ability of CRF_07BC declined by I132L mutation. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;I132L;T139K;T139R 59;198;69;69 64;203;76;76 NNRTI 112 118 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. However, compared to wild type BC-WT, I132L/T139R mutations delayed the peak time to day 14 and 21. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;T139R 38;44 43;49 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. In subtype B, I132L increased EC50 by 3.91, 4.61, 6.38, 3.56 fold, T139K increased EC50 by 3.13, 1.78, 2.26, 2.10 fold, T139R increased EC50 by 5.79, 3.99, 5.78, 2.75 fold, respectively. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;T139K;T139R 14;67;120 19;72;125 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. In subtype CRF07_BC, I132L mutation increased EC50 by 2.55, 19.35, 28.05, 6.13 fold, T139K mutation increased EC50 by 4.67, 3.66, 7.35, 3.30 fold, and T139R mutation increased EC50 by 1.82, 4.69, 25.12, 1.89 fold, respectively. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;T139K;T139R 21;85;151 26;90;156 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. OBJECTIVE: To study the drug sensitivity and analyze the replication kinetics of HIV-1 B and CRF07_BC subtypes with I132L or T139K/R mutations. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;T139K;T139R 116;125;125 121;132;132 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. RESULTS: The mutated infectious clones were constructed including PNL4-3-RT-I132L, PNL4-3-RT-T139K and PNL4-3-RT-T139R. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;T139K;T139R 76;93;113 81;98;118 RT;RT;RT 73;90;110 75;92;112 26081708 [Replication kinetic properties of HIV-1 CRF_BC novel drug resistance associated mutations]. The I132L and T139K/R mutations in HIV-1 B and CRF07_BC infectious clones reduced their drug sensitivity to NNRTIs, which accompanied with the increase of EC50 (concentration for 50% of maximal effect). 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV I132L;T139K;T139R 4;14;14 9;21;21 NNRTI 108 114 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. VF was associated with emergence of usual nevirapine mutations (Y181C/I/D, K103N and V106A/I), M184V (n = 16; 12 with lamivudine vs. 2015 PloS one Abstract HIV M184V;Y181I 95;64 100;73 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. VF was associated with emergence of usual nevirapine mutations (Y181C/I/D, K103N and V106A/I), M184V (n = 16; 12 with lamivudine vs. 4 with emtricitabine, p = 0.04), and K65R (n = 7). 2015 PloS one Abstract HIV K65R;K103N;V106A;V106I;Y181C;Y181D 170;75;85;85;64;64 174;80;92;92;73;73 26108607 Analysis of early resistance development at the first failure timepoint in elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate-treated patients. M184V/I in RT was the first mutation to appear in many cases (n = 6) and was then followed by additional mutations in RT and IN. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 0;0 7;7 IN;RT;RT 125;11;118 127;13;120 26108607 Analysis of early resistance development at the first failure timepoint in elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate-treated patients. No case with development of resistance to the IN strand-transfer inhibitor prior to the development of M184V/I was detected. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 103;103 110;110 IN 46 48 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Emetine also blocked HIV-1 infection of RT M184V mutant. 2015 Molecules (Basel, Switzerland) Abstract HIV M184V 43 48 RT 40 42 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC) with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V). 2015 Molecules (Basel, Switzerland) Abstract HIV M184V 210 215 NRTI;RT 165;140 197;142 26111981 Drug resistance mutations 18 months after discontinuation of nevirapine-based ART for prevention of mother-to-child transmission of HIV in Malawi. RESULTS: Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. 2015 The Journal of antimicrobial chemotherapy Abstract HIV M184I 148 153 NNRTI 103 108 26117607 [Primary HIV resistance in Buenos Aires metropolitan area]. Mutations conferring low-level resistance to rilpivirine were found in 3 (3.3%) patients; such mutations were E138A and E138G. 2015 Medicina Abstract HIV E138A;E138G 110;120 115;125 26117607 [Primary HIV resistance in Buenos Aires metropolitan area]. The most frequent mutations were K103N and M41L. 2015 Medicina Abstract HIV K103N;M41L 33;43 38;47 26130028 Diverse mutants of HIV RRE IIB recognize wild-type Rev ARM or Rev ARM R35G-N40V. Despite the essential role of Rev asparagine 40 in recognition, the Rev ARM double-mutant R35G-N40V functions well in a Rev-RRE IIB reporter assay, indicating R35G-N40V uses a distinct recognition strategy. 2015 Journal of molecular recognition Abstract HIV N40V;N40V;R35G;R35G 95;164;90;159 99;168;94;163 Rev;Rev;Rev 30;68;120 33;71;123 26130028 Diverse mutants of HIV RRE IIB recognize wild-type Rev ARM or Rev ARM R35G-N40V. Originating from RRE IIB, as few as one or two substitutions are sufficient to confer specificity to wild-type Rev or Rev R35G-N40. 2015 Journal of molecular recognition Abstract HIV R35G 122 126 Rev;Rev 111;118 114;121 26130028 Diverse mutants of HIV RRE IIB recognize wild-type Rev ARM or Rev ARM R35G-N40V. The diversity of RRE IIB mutants that maintain binding to wild-type Rev ARM and R35G-N40V supports neutral theories of evolution and illustrates paths by which viral RNA-protein interactions can evolve new specificities. 2015 Journal of molecular recognition Abstract HIV N40V;R35G 85;80 89;84 Rev 68 71 26130028 Diverse mutants of HIV RRE IIB recognize wild-type Rev ARM or Rev ARM R35G-N40V. To examine how RRE IIB may evolve specificity to wild-type Rev ARM and R35G-N40V, 10 RRE IIB libraries, each completely randomized in overlapping regions, were screened with wild-type Rev ARM and R35G-N40V using a reporter system based on bacteriophage lambda N antitermination. 2015 Journal of molecular recognition Abstract HIV N40V;N40V;R35G;R35G 76;201;71;196 80;205;75;200 Rev;Rev 59;184 62;187 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. To identify mechanisms of LA resistance, we generated in vitro a mutant HIV-1 NL4.3LAresistant virus, which acquired seven mutations in the HIV-1 envelope glycoproteins: S160N, V170N, Q280H and R389T in gp120 and K77Q, N113D and H132Y in gp41. 2015 PloS one Abstract HIV H132Y;K77Q;N113D;Q280H;R389T;S160N;V170N 229;213;219;184;194;170;177 234;217;224;189;199;175;182 gp120;gp41;Env 203;238;146 208;242;154 26142476 Dolutegravir maintains a durable effect against HIV replication in tissue culture even after drug washout. In addition, we assessed the role of the R263K substitution within the integrase ORF that is associated with low-level resistance to dolutegravir. 2015 The Journal of antimicrobial chemotherapy Abstract HIV R263K 41 46 IN 71 80 26142476 Dolutegravir maintains a durable effect against HIV replication in tissue culture even after drug washout. The R263K substitution did not significantly impact on levels of RT activity after drug washout, suggesting that dolutegravir remained tightly bound to the integrase enzyme despite the presence of this mutation. 2015 The Journal of antimicrobial chemotherapy Abstract HIV R263K 4 9 IN;RT 156;65 165;67 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. 2016 Journal of medical virology Abstract HIV Q151M 80 85 26149983 Characterization of HIV-1 Resistance to Tenofovir Alafenamide In Vitro. In this study, selection of in vitro resistance to both TAF and the parent compound, TFV, led to the emergence of HIV-1 with the K65R amino acid substitution in RT with 6.5-fold-reduced susceptibility to TAF. 2015 Antimicrobial agents and chemotherapy Abstract HIV K65R 129 133 RT 161 163 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. Major protease inhibitor mutations and the reverse transcriptase mutation M184V were detected at VF in virus from 4 and 5 patients, respectively, across both studies. 2015 The open AIDS journal Abstract HIV M184V 74 79 RT;PR 43;6 64;14 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). 2015 PloS one Abstract HIV K103N;Y181C 62;81 67;86 26166507 Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization. Additionally, the single M434I mutation was sufficient for the enhanced neutralization of the virus by NMAbs, autologous plasma IgGs, and heterologous sera relative to that of the parental virus. 2016 Japanese journal of infectious diseases Abstract HIV M434I 25 30 26166507 Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization. The M434I mutation conferred the greatest neutralizing sensitivity among the 4 MVC-resistant mutations. 2016 Japanese journal of infectious diseases Abstract HIV M434I 4 9 26166507 Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization. The MVC-resistant variant acquired 4 sequential mutations in gp120: T297I, M434I, V200I, and K305R. 2016 Japanese journal of infectious diseases Abstract HIV K305R;M434I;T297I;V200I 93;75;68;82 98;80;73;87 gp120 61 66 26166507 Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization. The neutralization sensitivity of the variant greatly increased following its acquisition of the second mutation, M434I, in the C4 region. 2016 Japanese journal of infectious diseases Abstract HIV M434I 114 119 26166507 Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization. The virus with the first resistant mutation, T297I, was sensitive to all NMAbs, whereas the passage control virus was not. 2016 Japanese journal of infectious diseases Abstract HIV T297I 45 50 26166629 Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. The most potent compounds show below 10 nanomolar activity towards wild-type HIV-1 and variants bearing Tyr181Cys and Lys103Asn/Tyr181Cys resistance mutations. 2015 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C;Y181C 118;128;104 127;137;113 26175454 Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection. BACKGROUND: Virologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. 2016 The Journal of infectious diseases Abstract HIV K65R;M184V;T69del 242;262;250 246;267;256 26175454 Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. 2016 The Journal of infectious diseases Abstract HIV K65R;T69del 8;22 12;28 26175454 Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI. 2016 The Journal of infectious diseases Abstract HIV K65R;T69del 17;106 21;112 NRTI 184 188 26175454 Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection. Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations. 2016 The Journal of infectious diseases Abstract HIV K65R;T69del 37;46 41;52 26192603 The use of dried blood spot specimens for HIV-1 drug resistance genotyping in young children initiating antiretroviral therapy. Non-nucleoside reverse transcriptase inhibitor mutations were most commonly detected in both specimen types, particularly Y181C/I and K103N/S. 2015 Journal of virological methods Abstract HIV K103N;K103S;Y181C;Y181I 134;134;122;122 141;141;129;129 NNRTI 0 36 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. We review here the issue of drug resistance against integrase strand transfer inhibitors as well as both pre-clinical and clinical studies that have led to the identification of the R263K mutation in integrase as a signature resistance substitution for dolutegravir. 2015 Viruses Abstract HIV R263K 182 187 IN;IN 52;200 61;209 26198456 Understanding the basis of I50V-induced affinity decrease in HIV-1 protease via molecular dynamics simulations using polarized force field. I50V mutation as one of the most significant mutations occurring in HIV-1 protease will be investigated in this study. 2015 Journal of computational chemistry Abstract HIV I50V 0 4 PR 74 82 26198456 Understanding the basis of I50V-induced affinity decrease in HIV-1 protease via molecular dynamics simulations using polarized force field. In addition, the mechanism governing the decrease in the binding affinity of PI in the presence of I50V mutation was also explored to provide insights pertaining to the design of the next generation of anti-HIV drugs. 2015 Journal of computational chemistry Abstract HIV I50V 99 103 PI 77 79 26198456 Understanding the basis of I50V-induced affinity decrease in HIV-1 protease via molecular dynamics simulations using polarized force field. Molecular dynamics (MD) simulation was utilized to examine the effect of I50V mutation on the binding of two PIs namely indinavir and amprenavir to HIV-1 protease. 2015 Journal of computational chemistry Abstract HIV I50V 73 77 PR;PI 154;109 162;112 26200883 HIV-1 Genetic Diversity and Transmitted Drug Resistance Among Recently Infected Individuals at Men Who Have Sex with Men Sentinel Surveillance Points in Hebei Province, China. The rate of HIV-1 transmitted drug resistance (TDR) mutation (M46L) was 2.08% (1/48). 2015 AIDS research and human retroviruses Abstract HIV M46L 62 66 26205139 Combination of two pathways involved in raltegravir resistance confers dolutegravir resistance. CONCLUSIONS: Combination of N155H, G140S and Q148H mutations originating from two distinct resistance pathways to raltegravir or elvitegravir led to a high level of dolutegravir resistance. 2015 The Journal of antimicrobial chemotherapy Abstract HIV G140S;N155H;Q148H 35;28;45 40;33;50 26205139 Combination of two pathways involved in raltegravir resistance confers dolutegravir resistance. RESULTS: Our data showed that the combination of N155H, G140S and Q148H mutations led to strong resistance to dolutegravir. 2015 The Journal of antimicrobial chemotherapy Abstract HIV G140S;N155H;Q148H 56;49;66 61;54;71 26209397 Expansion of the CRF19_cpx Variant in Spain. Resistance mutations in the RT region were found in all sequences from group A (V139D) and in two sequences from group B (E138A). 2015 Journal of clinical virology Abstract HIV E138A;V139D 122;80 127;85 RT 28 30 26241860 The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon. The currently predominant viral population emerged in the 1980s, from an ancient population which had first developed in the 1950s, and is characterized by higher growth and evolutionary rates, and the natural presence of the Y181C resistance mutation, thought to confer a phenotypic advantage. 2015 PLoS pathogens Abstract HIV Y181C 226 231 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. CONCLUSIONS: The R263K substitution is more deleterious to integrase strand-transfer activity and viral infectiousness in HIV-1 subtype C than in subtype B. 2015 AIDS (London, England) Abstract HIV R263K 17 22 IN 59 68 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. DESIGN AND METHODS: We used cell-free strand transfer assays and tissue culture experiments to characterize the R263K substitution in HIV-1 subtype C integrase in comparison with subtype B. 2015 AIDS (London, England) Abstract HIV R263K 112 117 IN 150 159 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. R263K in HIV-1 subtype C also conferred low levels of resistance against dolutegravir and high levels of cross-resistance against elvitegravir, but not raltegravir. 2015 AIDS (London, England) Abstract HIV R263K 0 5 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. RESULTS: Cell-free biochemical assays showed that the R263K substitution diminished subtype C integrase strand-transfer activity by decreasing the affinity of integrase for target DNA. 2015 AIDS (London, England) Abstract HIV R263K 54 59 IN;IN 94;159 103;168 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. Similarly, both viral infectiousness and replication capacity were reduced by the R263K substitution in tissue culture. 2015 AIDS (London, England) Abstract HIV R263K 82 87 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. The objective of this study was to characterize the R263K substitution in HIV-1 subtype C integrase. 2015 AIDS (London, England) Abstract HIV R263K 52 57 IN 90 99 26244385 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. The R263K substitution in integrase was identified through culture selection as a resistance-associated substitution for dolutegravir and was recently detected in two treatment-experienced participants in the SAILING clinical trial, who experienced dolutegravir-based treatment failure, one of whom was infected by a subtype C virus. 2015 AIDS (London, England) Abstract HIV R263K 4 9 IN 26 35 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. However, viral infectivity was significantly decreased from that of NL4.3IN(N155H/R263K) after the addition of each tertiary mutation, and no increases in levels of DTG resistance were observed. 2015 Journal of virology Abstract HIV N155H;R263K 76;82 81;87 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. Since many patients failing RAL/EVG are given DTG as part of rescue therapy, and given that the N155H substitution often is found in combination with other compensatory resistance mutations in such individuals, we investigated the effects of multiple such substitutions within integrase (IN) on each of integrase function, HIV-1 infectivity, and levels of drug resistance. 2015 Journal of virology Abstract HIV N155H 96 101 IN;IN;IN 277;303;288 286;312;290 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. Therefore, the current study aimed to uncover whether accessory mutations that appear after N155H in response to raltegravir/elvitegravir were compatible with N155H and R263K. 2015 Journal of virology Abstract HIV N155H;N155H;R263K 92;159;169 97;164;174 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. These data support the hypothesis that primary resistance against DTG cannot evolve through RAL/EVG resistance pathways and that the selection of R263K leads HIV into an evolutionary dead-end. 2015 Journal of virology Abstract HIV R263K 146 151 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. This work shows that the compensatory mutations that evolve after N155H under continued DTG or RAL/EVG pressure in patients are unable to improve either enzyme efficiency or viral infectivity in an N155H/R263K background. 2015 Journal of virology Abstract HIV N155H;N155H;R263K 66;198;204 71;203;209 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. To this end, each of the L74M, E92Q, T97A, E157Q, and G163R substitutions were introduced into NL4.3 subtype B HIV-1 vectors harboring N155H and R263K in tandem [termed NL4.3IN(N155H/R263K)]. 2015 Journal of virology Abstract HIV E157Q;E92Q;G163R;L74M;N155H;N155H;R263K;R263K;T97A 43;31;54;25;177;135;183;145;37 48;35;59;29;182;140;188;150;41 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. UNLABELLED: We have previously shown that the addition of the raltegravir/elvitegavir (RAL/EVG) primary resistance mutation N155H to the R263K dolutegravir (DTG) resistance mutation partially compensated for the fitness cost imposed by R263K while also slightly increasing DTG resistance in vitro (K. 2015 Journal of virology Abstract HIV N155H;R263K;R263K 124;137;236 129;142;241 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. We found that the addition of T97A, E157Q, or G163R somewhat improved the affinity of INN155H/R263K for its target DNA substrate, while the presence of L74M or E92Q had a negative effect on this process. 2015 Journal of virology Abstract HIV E157Q;E92Q;G163R;L74M;N155H;R263K;T97A 36;160;46;152;88;94;30 41;164;51;156;93;99;34 IN 86 88 26246578 Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity. We had previously shown that HIV containing the primary raltegravir/elvitegravir resistance substitution N155H could select for R263K under dolutegravir pressure and that this virus was fit and displayed low-level resistance to dolutegravir (Anstett et al., J Virol 89: 4681-4684). 2015 Journal of virology Abstract HIV N155H;R263K 105;128 110;133 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. RESULTS: By examining Env mutants with changes in the ectodomain of the protein (virus ROD14) or the cytoplasmic tail (substitution Y707A) that render the proteins unable to counteract tetherin, we determined that an interaction between Env and tetherin is important for this activity. 2015 Retrovirology Abstract HIV Y707A 132 137 Env;Env 22;237 25;240 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. CONCLUSION: Both the modest resistance conferred by K65R and the high TFV-DP exposure in vaginal lymphocytes, likely explain the observed protection. 2015 Retrovirology Abstract HIV K65R 52 56 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. Here we investigated efficacy of the TFV gel against vaginal transmission of a TFV-resistant SHIV containing the K65R mutation (SHIV162P3K65R) and its relationship to drug levels in vaginal tissues. 2015 Retrovirology Abstract HIV K65R 113 117 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. The findings in this model do not predict complete loss of protection by topical TFV against vaginal exposure to HIV-1K65R viruses and provide a tissue drug target for high efficacy. 2015 Retrovirology Abstract HIV K65R 118 122 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Before bPI, significant variation in Protease and Gag was observed at positions previously associated with PI exposure and resistance including Gag mutations L449P, S451N, and L453P and Protease K20I and L63P. 2015 AIDS research and human retroviruses Abstract HIV K20I;L449P;L453P;L63P;S451N 195;158;176;204;165 199;163;181;208;170 PR;PR;Gag;Gag;PI 37;186;50;144;107 45;194;53;147;109 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Following PI failure, previously described mutations in Protease and Gag were observed, including those at the cleavage sites such as R361K and P453L. 2015 AIDS research and human retroviruses Abstract HIV P453L;R361K 144;134 149;139 PR;Gag;PI 56;69;10 64;72;12 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. At time of virological failure, genotypic resistance-associated mutations were detected in three participants, two with E138K (one alone and one with additional mutations). 2016 Antiviral therapy Abstract HIV E138K 120 125 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. All carried R5-tropic viruses, with evidence of atypical or resistance amino-acidic mutations related to NNRTI-drugs (K103Q in C-cluster, and K101E+E138K in CRF17_BF-cluster). 2015 PloS one Abstract HIV E138K;K101E;K103Q 148;142;118 153;147;124 NNRTI 105 110 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Minor PI mutations including A71T, G48E, G48R, I13V, K20I, K20R, L10I, L10V, L33F, L63P, T74S, V11I, and V32L were detected among the ART-experienced (36.2 vs. 2015 AIDS research and therapy Abstract HIV A71T;G48E;G48R;I13V;K20I;K20R;L10I;L10V;L33F;L63P;T74S;V11I;V32L 29;35;41;47;53;59;65;71;77;83;89;95;105 33;39;45;51;57;63;69;75;81;87;93;99;109 PI 6 8 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. RESULTS: Only IDUs harboured major PI resistance mutations consisting of L90M, M46I and D30 N among 3 (6.4 %) ART-experienced and 1 (3.1 %) -naive individuals. 2015 AIDS research and therapy Abstract HIV D30N;L90M;M46I 88;73;79 93;77;83 PI 35 37 26291050 Prevalence of drug resistance mutations in HAART patients infected with HIV-1 CRF06_cpx in Estonia. Additionally, CRF06_cpx specific mutation E179V and substitutions R32K, K122E, and V200AE were also detected in treatment experienced population. 2016 Journal of medical virology Abstract HIV E179V;K122E;R32K;V200A;V200E 42;72;66;83;83 47;77;70;89;89 26291050 Prevalence of drug resistance mutations in HAART patients infected with HIV-1 CRF06_cpx in Estonia. Sub-population analysis revealed that EFV + 3TC + ddI failed patients had more DRMs compared to EFV + 3TC + ZDV failed patients, especially the ddI DRM L74IV and several additional NNRTI DRMs. 2016 Journal of medical virology Abstract HIV L74I;L74V 152;152 157;157 NNRTI 181 186 26291050 Prevalence of drug resistance mutations in HAART patients infected with HIV-1 CRF06_cpx in Estonia. The most common NRTI mutations were M184V (80%), L74V (31%), L74I (17%), K219E (9%), and M184I (9%), NNRTI mutations were K103N (83%), P225H (14%), L100I (11%), and Y188L (11%), reflecting generally the similar pattern of DRMs to that seen in treatment failed subtype B viruses. 2016 Journal of medical virology Abstract HIV K103N;K219E;L100I;L74I;L74V;M184I;M184V;P225H;Y188L 122;73;148;61;49;89;36;135;165 127;78;153;65;53;94;41;140;170 NNRTI;NRTI 101;16 106;20 26296335 Frequency of transmitted drug resistance mutations among treatment-naive HIV-1-infected individuals at a tertiary care centre in South India. Based on the CPR tool, three strains (2.4 %) had TDRMs, and these were K101E, Y181C and G190A. 2015 Molecular diagnosis & therapy Abstract HIV G190A;K101E;Y181C 88;71;78 93;76;83 26305669 Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in mice. Interestingly, the wild type CyPA markedly increased Gag cellular immunity, but the H54Q and F60A mutants drastically reduced CyPA adjuvant activation. 2016 Human vaccines & immunotherapeutics Abstract HIV F60A;H54Q 93;84 97;88 Gag 53 56 26305669 Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in mice. To investigate the mechanisms of the adjuvant effect, site-directed mutagenesis in CyPA, including active site residues H54Q and F60A resulted in mutants that were co-expressed with Gag in dual cassettes. 2016 Human vaccines & immunotherapeutics Abstract HIV F60A;H54Q 129;120 133;124 Gag 182 185 26305833 Discordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failure. A total of 141 unique mutational patterns were observed, with N155H (25.4%), Q148H (16.2%) and Y143R (8.3%) the most prevalent signature mutations. 2015 Journal of clinical virology Abstract HIV N155H;Q148H;Y143R 62;77;95 67;82;100 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL), 113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255, 17.6%), Q148H/R/K + G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%). 2015 The Journal of antimicrobial chemotherapy Abstract HIV G140A;G140S;N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 175;175;140;163;163;163;203;203;203 182;182;145;172;172;172;212;212;212 IN 116 119 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Comparing subtype B with non-B clades, Q148H/R/K occurred in 42/209 (20.1%) versus 2/46 (4.3%) subjects (P = 0.009) and G140S/A occurred in 36/209 (17.2%) versus 1/46 (2.2%) subjects (P = 0.005). 2015 The Journal of antimicrobial chemotherapy Abstract HIV G140A;G140S;Q148H;Q148K;Q148R 120;120;39;39;39 127;127;48;48;48 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. In addition, four (1.6%) raltegravir recipients showed novel mutations at recognized resistance sites (E92A, S147I, N155D, N155Q) and novel mutations at other integrase positions that were statistically associated with raltegravir exposure (K159Q/R, I161L/M/T/V, E170A/G). 2015 The Journal of antimicrobial chemotherapy Abstract HIV E170A;E170G;E92A;I161L;I161M;I161T;I161V;K159Q;K159R;N155D;N155Q;S147I 263;263;103;250;250;250;250;241;241;116;123;109 270;270;107;261;261;261;261;248;248;121;128;114 IN 159 168 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Reduced occurrence of Q148H/R/K + G140S/A was seen in non-B clades versus subtype B, and was explained by the higher genetic barrier to the G140S mutation observed in all non-B clades analysed. 2015 The Journal of antimicrobial chemotherapy Abstract HIV G140A;G140S;G140S;Q148H;Q148K;Q148R 34;34;140;22;22;22 41;41;145;31;31;31 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. E138K is a common secondary substitution observed with various primary resistance substitutions in RAL- and EVG-treated individuals. 2015 Journal of virology Abstract HIV E138K 0 5 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. HIV drug-resistant mutations in integrase that can arise in individuals treated with elvitegravir commonly include the T66I substitution, whereas R263K is a signature resistance substitution against dolutegravir. 2015 Journal of virology Abstract HIV R263K;T66I 146;119 151;123 IN 32 41 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. In order to determine how different combinations of integrase resistance mutations can influence the outcome of therapy, we report here the effects of the T66I, E138K, and R263K substitutions, alone and in combination, on viral replicative capacity and resistance to integrase inhibitors. 2015 Journal of virology Abstract HIV E138K;R263K;T66I 161;172;155 166;177;159 IN;IN 52;267 61;276 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. Our observations support the use of DTG in second-line therapy for individuals who experience treatment failure with EVG due to the T66I substitution. 2015 Journal of virology Abstract HIV T66I 132 136 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. Our results show that the addition of R263K to the T66I substitution diminishes viral replicative capacity and strand transfer activity while not compromising susceptibility to dolutegravir. 2015 Journal of virology Abstract HIV R263K;T66I 38;51 43;55 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. T66I is a substitution that is common in individuals who have developed resistance against a different INSTI termed elvitegravir (EVG), but it is not known whether these two mutations might be compatible in the context of resistance against DTG or what impact the combination of these substitutions might have on resistance against INSTIs. 2015 Journal of virology Abstract HIV T66I 0 4 INSTI;INSTI 103;332 108;338 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. The addition of the E138K substitution partially compensated for these deficits and resulted in high levels of resistance against EVG but not against DTG or RAL. 2015 Journal of virology Abstract HIV E138K 20 25 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. The combination of the R263K and T66I substitutions decreased HIV-1 infectivity, replicative capacity, and strand transfer activity. 2015 Journal of virology Abstract HIV R263K;T66I 23;33 28;37 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. The R263K substitution seems to be incompatible with the presence of common resistance mutations associated with raltegravir (RAL), a different integrase strand transfer inhibitor (INSTI). 2015 Journal of virology Abstract HIV R263K 4 9 IN;INSTI 144;181 153;186 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. These findings suggest that the presence of the T66I substitution will not compromise the activity of DTG and may also help to prevent the additional generation of the R263K mutation. 2015 Journal of virology Abstract HIV R263K;T66I 168;48 173;52 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. This supports the use of dolutegravir in second-line therapy for patients failing elvitegravir therapy who harbor the T66I resistance substitution. 2015 Journal of virology Abstract HIV T66I 118 122 26311878 The Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance. UNLABELLED: The R263K substitution in integrase has been selected in tissue culture with dolutegravir (DTG) and has been reported for several treatment-experienced individuals receiving DTG as part of salvage therapy. 2015 Journal of virology Abstract HIV R263K 16 21 IN 38 47 26311893 Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers. The addition of a 20-residue flexible linker (FL20) between the gp120 and gp41 ectodomain (gp41ECTO) subunits to make the uncleaved 92UG037.8 gp140-FL20 construct is not sufficient to create a native-like trimer, but a small percentage of native-like trimers were produced when an I559P substitution in gp41ECTO was also present. 2015 Journal of virology Abstract HIV I559P 281 286 gp41;gp41;gp120;gp140;gp41 91;303;64;142;74 95;307;69;147;78 26313923 Synthesis and Antiviral Evaluation of 1-[(2-Phenoxyethyl)oxymethyl] and 6-(3,5-Dimethoxybenzyl) Analogues of HIV Drugs Emivirine and TNK-651. The newly synthesized non-nucleosides were tested for antiviral activity against wild type HIV-1 IIIB as well as the resistant strains N119 (Y181C), A17 (K103N+Y181C), and the triple mutant EFV(R) (K103R+V179D+P225H) in MT-4 cells. 2016 Drug research Abstract HIV K103N;K103R;P225H;V179D;Y181C;Y181C 154;198;210;204;141;160 159;203;215;209;146;165 26317593 A Comparative Insight into Amprenavir Resistance of Mutations V32I, G48V, I50V, I54V, and I84V in HIV-1 Protease Based on Thermodynamic Integration and MM-PBSA Methods. Drug resistance of mutations V32I, G48V, I50V, I54V, and I84V in HIV-1 protease (PR) was found in clinical treatment of HIV patients with the drug amprenavir (APV). 2015 Journal of chemical information and modeling Abstract HIV G48V;I50V;I54V;I84V;V32I 35;41;47;57;29 39;45;51;61;33 PR;PR 71;81 79;83 26322949 One-Step Ligation on RNA Amplification for the Detection of Point Mutations. LRA achieved a limit of specific quantitation of 1:100 (1%), and a limit of specific detection for mutant K103N RNA transcripts among excess wild-type strands of 1:10,000 (0.01%). 2015 The Journal of molecular diagnostics Abstract HIV K103N 106 111 26322949 One-Step Ligation on RNA Amplification for the Detection of Point Mutations. LRA also exhibited good detection threshold of 5 x 10(2) copies/muL K103N RNA transcripts. 2015 The Journal of molecular diagnostics Abstract HIV K103N 68 73 26322949 One-Step Ligation on RNA Amplification for the Detection of Point Mutations. We applied LRA to the detection of a common, clinically relevant HIV-1 reverse transcriptase drug-resistant point mutation, K103N, and compared it with allele-specific PCR and pyrosequencing. 2015 The Journal of molecular diagnostics Abstract HIV K103N 124 129 RT 71 92 26324274 Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase. In this study, the roles of these mutations, in combination with T215Y, were examined to determine whether they affect polymerization and excision by HIV-1 RT. 2015 Antimicrobial agents and chemotherapy Abstract HIV T215Y 65 70 RT 156 158 26324274 Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase. The L210W mutation plays a similar role, but it enhances excision by RTs that carry the T215Y mutation when ATP is present at a low concentration. 2015 Antimicrobial agents and chemotherapy Abstract HIV L210W;T215Y 4;88 9;93 RT 69 72 26324274 Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase. The M41L mutation appears to help restore the DNA polymerization activity of RT containing the T215Y mutation and also enhances AZTMP excision. 2015 Antimicrobial agents and chemotherapy Abstract HIV M41L;T215Y 4;95 8;100 RT 77 79 26324274 Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase. The primary resistance pathway selects for mutations of T215 that change the threonine to either a tyrosine or a phenylalanine (T215Y/F); this resistance pathway involves an ATP-dependent excision mechanism. 2015 Antimicrobial agents and chemotherapy Abstract HIV T215F;T215Y 128;128 135;135 26324274 Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W in HIV-1 Reverse Transcriptase. The T215Y AZT resistance mutation is often accompanied by two other mutations, M41L and L210W. 2015 Antimicrobial agents and chemotherapy Abstract HIV L210W;M41L;T215Y 88;79;4 93;83;9 26351907 The double mutation L109M and R448M of HIV-1 reverse transcriptase decreases fidelity of DNA synthesis by promoting mismatch elongation. Furthermore, we were able to explain the prevalence of transition mutations with the finding that HIV-1 RT variant L109M/R448M preferred misincorporation of C opposite A and elongation of C:A mismatches. 2015 Biological chemistry Abstract HIV L109M;R448M 115;121 120;126 RT 104 106 26355081 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. Moreover, target cells infected with HIV-1-NefE24Q-Q107R were recognized better by HIV-specific T cells than those infected with HIV-1NL4.3 or single Nef mutants. 2015 Journal of virology Abstract HIV E24Q;Q107R 46;51 50;56 Nef;Nef 43;150 46;153 26355081 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. Most notably, we identify a novel escape-driven fitness defect: B*13-driven substitutions E24Q and Q107R in Nef, when present together, substantially impair this protein's ability to downregulate HLA class I. 2015 Journal of virology Abstract HIV E24Q;Q107R 90;99 94;104 Nef 108 111 26355081 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. Single Nef mutations did not affect CD4 or HLA downregulation; however, the Nef double mutant E24Q-Q107R showed 40% impairment in HLA downregulation with no evidence of Nef stability defects. 2015 Journal of virology Abstract HIV E24Q;Q107R 94;99 98;104 Nef;Nef;Nef 7;76;169 10;79;172 26355081 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. The Gag-I437L-mediated replication defect was rescued to wild-type levels by the adjacent K436R mutation. 2015 Journal of virology Abstract HIV I437L;K436R 8;90 13;95 Gag 4 7 26355081 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. We also identify Gag-I147L, the most rapidly and commonly selected B*13-driven substitution in HIV-1, as a putative C-terminal anchor residue mutation in a novel B*13 epitope. 2015 Journal of virology Abstract HIV I147L 21 26 Gag 17 20 26355081 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. We extend our knowledge of the impact of B*13-driven escape on HIV-1 replication by identifying Gag-K436R as a compensatory mutation for the fitness-costly Gag-I437L. 2015 Journal of virology Abstract HIV I437L;K436R 160;100 165;105 Gag;Gag 96;156 99;159 26355081 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. When tested individually, only Gag-I147L and Gag-I437L incurred replicative costs (5% and 17%, respectively), consistent with prior reports. 2015 Journal of virology Abstract HIV I147L;I437L 35;49 40;54 Gag;Gag 31;45 34;48 26355316 MOLECULAR TRACING OF HETEROSEXUAL HIV-1 TRANSMISSION IN GEORGIA. Of these 16 events, viruses from 14 pairs had genetic distance less than 0.015.Mutation A62V was seen in samples from 5 pairs, of them samples from 4 pairs additionally had V77I mutation. 2015 Georgian medical news Abstract HIV A62V;V77I 88;173 92;177 26355570 A phylotype-based analysis highlights the role of drug-naive HIV-positive individuals in the transmission of antiretroviral resistance in the UK. The most commonly transmitted mutations were L90M in the protease gene and K103N, T215D and T215S in reverse transcriptase. 2015 AIDS (London, England) Abstract HIV K103N;L90M;T215D;T215S 75;45;82;92 80;49;87;97 RT;PR 101;57 122;65 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. RESULTS: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers - above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. 2015 AIDS (London, England) Abstract HIV D30N;G190A;G190E;G190S;L90M;M184I;M184V;N88D;N88S 157;182;182;182;171;207;207;163;163 161;191;191;191;176;214;214;169;169 RT;RT 178;203 180;205 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. According to ARV used in these individuals, we focused on the following seven reverse transcriptase inhibitor-resistant mutations: M41L, K65R, K70R, K103N, Y181C, M184V, and T215F/Y. 2015 PloS one Abstract HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y;Y181C 149;137;143;163;131;174;174;156 154;141;147;168;135;181;181;161 RT 78 99 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Phylogenetic analysis indicated that pre-existing K103N and T215I variants had close genetic relationships with high-frequency K103N and T215I observed during treatment. 2015 PloS one Abstract HIV K103N;K103N;T215I;T215I 50;127;60;137 55;132;65;142 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. RESULTS: The use of AS-PCR enabled detection of the drug-resistant mutations, M41L, K103N, Y181C, M184V and T215Y, present as low-frequency populations in five of the six individuals. 2015 PloS one Abstract HIV K103N;M184V;M41L;T215Y;Y181C 84;98;78;108;91 89;103;82;113;96 26372484 The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. CONCLUSION: The DTG-resistant R263K substitution antagonized the development of HIV-1 resistance against RAL while partially facilitating the occurrence of resistance against EVG. 2015 AIDS (London, England) Abstract HIV R263K 30 35 26372484 The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. DESIGN AND METHODS: We performed tissue culture selection experiments using DTG-resistant viruses containing integrase substitutions at positions R263K, H51Y/R263K, E138K/R263K, G118R and H51Y/G118R in the presence of increasing concentrations of either RAL or EVG. 2015 AIDS (London, England) Abstract HIV E138K;G118R;G118R;H51Y;H51Y;R263K;R263K;R263K 165;178;193;188;153;158;171;146 170;183;198;192;157;163;176;151 IN 109 118 26372484 The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. In contrast, resistance against EVG appeared earlier than in wild-type virus in viruses containing the R263K and E138K/R263K DTG-associated resistance substitutions. 2015 AIDS (London, England) Abstract HIV E138K;R263K;R263K 113;103;119 118;108;124 26372484 The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. RESULTS: The presence of the R263K substitution delayed the emergence of resistance against RAL whereas the simultaneous presence of either the H51Y or E138K secondary substitutions in combination with R263K somewhat mitigated this inhibitory effect. 2015 AIDS (London, England) Abstract HIV E138K;H51Y;R263K;R263K 152;144;29;202 157;148;34;207 26372484 The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. The most common substitution in integrase under those circumstances is R263K whereas another substitution that was selected against DTG in tissue culture was G118R. 2015 AIDS (London, England) Abstract HIV G118R;R263K 158;71 163;76 IN 32 41 26378179 Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239. Both viruses and enzymes containing Q148R and G140S Q148R showed moderate levels of resistance against DTG. 2015 Journal of virology Abstract HIV G140S;Q148R;Q148R 46;36;52 51;41;57 26378179 Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239. RAL and EVG showed reduced activity against both viruses and against enzymes containing Q148R, E92Q Y143R, and G140S Q148R. 2015 Journal of virology Abstract HIV E92Q;G140S;Q148R;Q148R;Y143R 95;111;117;88;100 99;116;122;93;105 26378179 Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239. The results show that the G118R and G140S Q148R substitutions decreased Km' and Vmax'/Km' for strand transfer compared to those of the WT. 2015 Journal of virology Abstract HIV G118R;G140S;Q148R 26;36;42 31;41;47 26378179 Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239. To study this at a biochemical level, purified recombinant SIVmac239 wild-type (WT) and E92Q, T97A, G118R, Y143R, Q148R, N155H, R263K, E92Q T97A, E92Q Y143R, R263K H51Y, and G140S Q148R recombinant substitution-containing IN enzymes were produced, and each of the characteristics strand transfer, 3'-processing activity, and INSTI inhibitory constants was assessed in cell-free assays. 2015 Journal of virology Abstract HIV E92Q;E92Q;E92Q;G118R;G140S;H51Y;N155H;Q148R;Q148R;R263K;R263K;T97A;T97A;Y143R;Y143R 88;135;146;100;174;164;121;114;180;128;158;94;140;107;151 92;139;150;105;179;168;126;119;185;133;163;98;144;112;156 INSTI;IN 325;222 330;224 26378179 Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239. We now show that 22 weeks of selection pressure with DTG yielded a mutation at position R263K in SIV, similar to what has been observed in HIV, and that selections with EVG led to emergence of the E92Q substitution, which is a primary INSTI resistance mutation in HIV associated with EVG treatment failure. 2015 Journal of virology Abstract HIV E92Q;R263K 197;88 201;93 INSTI 235 240 26385878 Patterns of HIV-1 Drug-Resistance Mutations among Patients Failing First-Line Antiretroviral Treatment in South India. RESULTS: Of the study patients followed up for 6 months, 23 patients failed first-line therapy and the mutation of I135R/T/V/X, L178 I/M, M184V/I, D67N, K70R, and K103N was most common. 2016 Journal of the International Association of Providers of AIDS Care Abstract HIV D67N;I135R;I135T;I135V;I135X;K103N;K70R;L178I;L178M;M184I;M184V 147;115;115;115;115;163;153;128;128;138;138 151;126;126;126;126;168;157;136;136;145;145 26392486 The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1. BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. 2015 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V;Q151M 115;168;124 119;173;129 RT 133 154 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Two crystal structures of ligand-free PR20 with the D25N mutation of the catalytic aspartate (PR20D25N) revealed three dimers with different flap conformations. 2015 Journal of molecular graphics & modelling Abstract HIV D25N 52 56 PR 38 40 26401032 Interaction between Reverse Transcriptase and Integrase Is Required for Reverse Transcription during HIV-1 Replication. We found that six viral clones bearing such IN substitutions (R231E, W243E, G247E, A248E, V250E, and I251E) were noninfectious. 2015 Journal of virology Abstract HIV A248E;G247E;I251E;R231E;V250E;W243E 83;76;101;62;90;69 88;81;106;67;95;74 IN 44 46 26401720 Prevalence of Transmitted Drug Resistance Mutations in HIV-1-Infected Drug-Naive Patients from Urban and Suburban Regions of Kenya. Among these mutations, L33I was the most prevalent mutation. 2016 AIDS research and human retroviruses Abstract HIV L33I 23 27 26404079 Transmitted drug resistance of HIV-1 strains among individuals attending voluntary counselling and testing in Taiwan. Among the seven major integrase mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R and N155H), only one strain harbouring the Q148R mutation was detected. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E92Q;G140S;N155H;Q148H;Q148K;Q148R;Q148R;S147G;T66I;Y143C;Y143H;Y143R 49;55;94;80;80;80;133;73;43;62;62;62 53;60;99;89;89;89;138;78;47;71;71;71 IN 22 31 26412111 Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE. At failure, two patients without NNRTI RAMs by PS carried minority rilpivirine RAMs K101E and/or E138K; and five additional patients carried other minority NNRTI RAMs V90I, V106I, V179I, V189I, and Y188H. 2016 Journal of medical virology Abstract HIV E138K;K101E;V106I;V179I;V189I;V90I;Y188H 97;84;173;180;187;167;198 102;89;178;185;192;171;203 NNRTI;NNRTI 33;156 38;161 26412111 Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE. Baseline minority nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs M184V and L210W were each detected in one VF (none in responders). 2016 Journal of medical virology Abstract HIV L210W;M184V 94;84 99;89 RT;NRTI 40;73 61;77 26412111 Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE. Linkage analysis showed that E138K and K101E were usually not observed on the same viral genome. 2016 Journal of medical virology Abstract HIV E138K;K101E 29;39 34;44 26412111 Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE. No baseline minority rilpivirine RAMs were detected in VFs; one responder carried 1.9% F227C. 2016 Journal of medical virology Abstract HIV F227C 87 92 26414430 High Prevalence of HIV Low Abundance Drug-Resistant Variants in a Treatment-Naive Population in North Rift Kenya. The most prevalent mutation was NRTI position K219Q/R (11/46, 24%) followed by NRTI M184V (5/46, 11%) and NNRTI K103N (4/46, 9%). 2015 AIDS research and human retroviruses Abstract HIV K103N;K219Q;K219R;M184V 112;46;46;84 117;53;53;89 NNRTI;NRTI;NRTI 106;32;79 111;36;83 26414663 HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey. However, TAMs were divided into three categories and M41L, L210W, and T215Y mutations were found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L + K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in 22 (1.7%) patients, respectively. 2016 AIDS research and human retroviruses Abstract HIV D67N;K219E;K219N;K219N;K219Q;K219R;K70R;L210W;M41L;M41L;M41L;T215C;T215C;T215D;T215D;T215F;T215S;T215S;T215Y 129;141;141;242;141;141;135;59;53;235;252;165;259;165;259;154;165;259;70 133;152;152;247;152;152;139;64;57;239;256;174;268;174;268;159;174;268;75 26414663 HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey. Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M). 2016 AIDS research and human retroviruses Abstract HIV G190A;G190E;G190S;I50V;I54V;I84V;K101E;K101P;K103N;K103S;L100I;L76V;L90M;M46L;N83D;Q58E;V179F;V82A;V82C;V82L;V82T;Y181C;Y181I;Y188H;Y188L;Y188M 165;165;165;261;267;303;116;116;125;125;109;279;313;255;297;273;134;285;285;285;285;152;152;141;141;141 174;174;174;265;271;307;123;123;132;132;114;283;317;259;301;277;139;295;295;295;295;159;159;150;150;150 NNRTI;PR 0;189 35;197 26414663 HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey. Primary drug resistance mutations (K65R, M184V) and thymidine analogue-associated mutations (TAMs) were evaluated together as nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations. 2016 AIDS research and human retroviruses Abstract HIV K65R;M184V 35;41 39;46 NRTI;NRTI 126;173 161;177 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. We estimated that mutations conferring isoniazid and streptomycin resistance in this clone were acquired 50 y prior to the Tugela Ferry outbreak (katG S315T [isoniazid]; gidB 130 bp deletion [streptomycin]; 1957 [95% highest posterior density (HPD): 1937-1971]), with the subsequent emergence of MDR and XDR occurring 20 y (rpoB L452P [rifampicin]; pncA 1 bp insertion [pyrazinamide]; 1984 [95% HPD: 1974-1992]) and 10 y (rpoB D435G [rifampicin]; rrs 1400 [kanamycin]; gyrA A90V [ofloxacin]; 1995 [95% HPD: 1988-1999]) prior to the outbreak, respectively. 2015 PLoS medicine Abstract HIV A90V;D435G;L452P;S315T 474;427;329;151 478;432;334;156 26424460 Baseline HIV-1 resistance, virological outcomes, and emergent resistance in the SECOND-LINE trial: an exploratory analysis. Emergent resistance was associated with the raltegravir group (OR 2.47, 95% CI 1.02-5.99; p=0.05), baseline log10 viral load (1.83, 1.12-2.97; p=0.02), and absence of the Lys65Arg (K65R) or Lys70Glu (K70E) mutation at baseline (3.18, 1.12-9.02; p=0.03). 2015 The lancet. HIV Abstract HIV K65R;K65R;K70E;K70E 171;181;190;200 179;185;198;204 26428230 Characteristics of Transmitted Drug-Resistant HIV-1 in Recently Infected Treatment-Naive Patients in Japan. Common mutations in both groups were M46I/L and T215 revertants. 2016 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M46I;M46L 37;37 43;43 26428230 Characteristics of Transmitted Drug-Resistant HIV-1 in Recently Infected Treatment-Naive Patients in Japan. Furthermore, sequences with these mutations, K103N and D30N/N88D formed clusters on phylogenetic trees. 2016 Journal of acquired immune deficiency syndromes (1999) Abstract HIV D30N;K103N;N88D 55;45;60 59;50;64 26428230 Characteristics of Transmitted Drug-Resistant HIV-1 in Recently Infected Treatment-Naive Patients in Japan. The phylogenetic clustering of cases with M46I/L or T215 revertants suggests that HIV with these mutations have become circulating strains. 2016 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M46I;M46L 42;42 48;48 26438501 Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. 2015 Antimicrobial agents and chemotherapy Abstract HIV E138G;E138Q 13;23 18;28 RT 0 2 26438501 Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. 2015 Antimicrobial agents and chemotherapy Abstract HIV E138G;E138Q 85;14 90;19 RT 20 22 26446597 Genetic Pathway of HIV-1 Resistance to Novel Fusion Inhibitors Targeting the Gp41 Pocket. In this study, the HIV-1 mutants resistant to MTSC22 were selected and characterized, which revealed that the E49K and L57R substitutions at the inhibitor-binding site and the N126K and E136G substitutions at the C-terminal heptad repeat region of gp41 critically determine the resistance phenotype. 2015 Journal of virology Abstract HIV E136G;E49K;L57R;N126K 186;110;119;176 191;114;123;181 gp41 248 252 26446597 Genetic Pathway of HIV-1 Resistance to Novel Fusion Inhibitors Targeting the Gp41 Pocket. Two mutations (E49K and L57R) located at the inhibitor-binding site and two mutations (N126K and E136G) located at the C-terminal heptad repeat region of gp41 were identified as conferring high resistance either singly or in combination. 2015 Journal of virology Abstract HIV E136G;E49K;L57R;N126K 97;15;24;87 102;20;28;93 gp41 154 158 26446597 Genetic Pathway of HIV-1 Resistance to Novel Fusion Inhibitors Targeting the Gp41 Pocket. Unlike E49K and N126K, which enhanced the stability of the endogenous viral six-helical bundle core (6-HB), L57R and E136G conversely destabilized the 6-HB structure. 2015 Journal of virology Abstract HIV E136G;E49K;L57R;N126K 117;7;108;16 122;11;112;21 26446597 Genetic Pathway of HIV-1 Resistance to Novel Fusion Inhibitors Targeting the Gp41 Pocket. While E49K reduced the C-terminal binding of inhibitors via an electrostatic repulsion, L57R dramatically disrupted the N-terminal binding of M-T hook structure and pocket-binding domain. 2015 Journal of virology Abstract HIV E49K;L57R 6;88 10;92 26458150 Prevalence of transmitted HIV-1 drug resistance among young adults attending HIV counselling and testing clinics in Kigali, Rwanda. Two participants (4%) had the K103N non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and one (2%) had the M46L protease inhibitor (PI) mutation. 2016 Antiviral therapy Abstract HIV K103N;M46L 30;121 35;125 NNRTI;PR;NNRTI;PI 36;126;84;146 72;134;89;148 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. METHODS: Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F). 2015 PloS one Abstract HIV K103N;K70R;M184V;T215F;T215Y;Y181C 164;158;178;185;185;171 169;162;183;192;192;176 RT 124 126 26469551 Adaptation of HIV-1 to rhTrim5alpha-mediated restriction in vitro. Furthermore, the escape mutations, predominantly in the capsid and p51 RT, altered viral sensitivity to modified huTrim5alpha R332P and R335G variants, with only a minor effect on the replication capacity in primary PBMCs. 2015 Virology Abstract HIV R332P;R335G 126;136 131;141 Capsid;RT 56;71 62;73 26470965 HIV reverse transcriptase gene mutations in anti-retroviral treatment naive rural people living with HIV/AIDS. The predominant polymorphisms detected were K122E (91.7%), V60I (91.7%), V35T (89%), Q207E (89%), D177E (89%), T200A (86.1%), S48T (83.33%), K173A (80.6%). 2015 Indian journal of medical microbiology Abstract HIV D177E;K122E;K173A;Q207E;S48T;T200A;V35T;V60I 98;44;141;85;126;111;73;59 103;49;146;90;130;116;77;63 26482266 Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants. APOBEC3G/F-associated E138K, M184I and M230I appeared within clonal sequences containing in-frame STOP codons in 2/3 (66%), 5/5 (100%) and 4/4 (100%) of the samples. 2016 Clinical microbiology and infection Abstract HIV E138K;M184I;M230I 22;29;39 27;34;44 26482266 Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants. In a large pan-European case-control study investigating the clinical relevance of pre-existing DRMVs using 454 pyrosequencing, the six most prevalent plasma DRMVs detected corresponded to G-to-A nucleotide mutations (V90I, V106I, V108I, E138K, M184I and M230I). 2016 Clinical microbiology and infection Abstract HIV E138K;M184I;M230I;V106I;V108I;V90I 238;245;255;224;231;218 243;250;260;229;236;222 26482266 Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants. Mutations E138K, M184I and M230I co-occurred in the same sequence as APOBEC3G/F signatures in 3/9 (33%), 5/11 (45%) and 4/8 (50%) of samples, respectively; such linkage was not found for V90I, V106I or V108I. 2016 Clinical microbiology and infection Abstract HIV E138K;M184I;M230I;V106I;V108I;V90I 10;17;27;193;202;187 15;22;32;198;207;191 26482266 Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants. Samples with minority E138K, M184I, and M230I mutations, but not those with V90I, V106I or V108I, were significantly associated with APOBEC3G/F activity (Fisher's P < 0.005), defined as the presence of > 0.5% of sample sequences with an APOBEC3G/F signature. 2016 Clinical microbiology and infection Abstract HIV E138K;M184I;M230I;V106I;V108I;V90I 22;29;40;82;91;76 27;34;45;87;96;80 26482309 Alkyl Amine Bevirimat Derivatives Are Potent and Broadly Active HIV-1 Maturation Inhibitors. However, naturally occurring polymorphisms in the SP1 region of Gag (e.g., SP1-V7A) led to a variable response in some BVM-treated patients. 2016 Antimicrobial agents and chemotherapy Abstract HIV V7A 79 82 SP1;SP1;Gag 50;75;64 53;78;67 26482309 Alkyl Amine Bevirimat Derivatives Are Potent and Broadly Active HIV-1 Maturation Inhibitors. We identified a set of derivatives that are markedly more potent than BVM against an HIV-1 clade B clone (NL4-3) and show robust antiviral activity against a variant of NL4-3 containing the V7A polymorphism in SP1. 2016 Antimicrobial agents and chemotherapy Abstract HIV V7A 190 193 SP1 210 213 26483513 Clinical, virological and phylogenetic characterization of a multiresistant HIV-1 strain outbreak in naive patients in southern Spain. BACKGROUND: We describe the characteristics of an HIV-1 strain with six viral reverse transcriptase mutations (D67N, T69N/D, V118I, V179D, T215S and K219Q), which we have called the Malaga strain. 2016 The Journal of antimicrobial chemotherapy Abstract HIV D67N;K219Q;T215S;T69D;T69N;V118I;V179D 111;149;139;117;117;125;132 115;154;144;123;123;130;137 RT 78 99 26487913 Design, Synthesis, and Biological Evaluation of 1,2-Dihydroisoquinolines as HIV-1 Integrase Inhibitors. Interestingly, these compounds showed similar ST inhibitory activity in G140S mutant, suggesting they can act against resistant strains. 2015 ACS medicinal chemistry letters Abstract HIV G140S 72 77 26487915 Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance. Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavirenz and rilpivirine. 2015 ACS medicinal chemistry letters Abstract HIV K101P 139 144 RT;RT 92;115 113;117 26487915 Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance. Comparison of wild-type structures and a new crystal structure of RT (K101P) in complex with a leading compound confirms that the K101P mutation is not a liability for the catechol diethers while suggesting that key interactions are lost with efavirenz and rilpivirine. 2015 ACS medicinal chemistry letters Abstract HIV K101P;K101P 70;130 75;135 RT 66 68 26487915 Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance. Kinetic data suggests that RT (K101P) variants are as catalytically fit as wild-type and thus can potentially increase in the viral population as more antiviral regimens include efavirenz or rilpivirine. 2015 ACS medicinal chemistry letters Abstract HIV K101P 31 36 RT 27 29 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Observed NRTIs resistance associated mutations were the lamivudine-induced mutation M184V (n = 4) and tenofovir associated mutation K65R (n = 1). 2015 PloS one Abstract HIV K65R;M184V 132;84 136;89 NRTI 9 14 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. The NNRTIs resistance associated mutations were K103N (n = 2), V106M, Y181S, Y188L, V90I, K101E and G190A (n = 1 each). 2015 PloS one Abstract HIV G190A;K101E;K103N;V106M;V90I;Y181S;Y188L 100;90;48;63;84;70;77 105;95;53;68;88;75;82 NNRTI 4 10 26521445 [HPLC enantioseparation, absolute configuration determination and anti-HIV-1 activity of (+/-)-F18 enantiomers]. Further investigation revealed that (R)-F18 and (S)-F18 shared a similar anti-HIV activities, however, (R)-F18 was more potent than (S)-F18 against wild-type virus, K101E mutation and P225H mutation pseudoviruses. 2015 Yao xue xue bao Abstract HIV K101E;P225H 165;184 170;189 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. 2014 Journal of AIDS & clinical research Abstract HIV K65R;K70R 95;46 99;50 NRTI 25 29 26529282 HIV-1 Genetic Diversity and Transmitted Drug Resistance in Antiretroviral Treatment-Naive Individuals from Amapa State, Northern Brazil. Only one TDRM (K103N) was detected in a single patient from our study population. 2016 AIDS research and human retroviruses Abstract HIV K103N 15 20 26537676 Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice. Here, we use cryo-electron tomography to show that, like MIs, the T8I mutation stabilizes the immature-like CA-SP1 lattice. 2016 Journal of virology Abstract HIV T8I 66 69 SP1;Capsid 111;108 114;110 26537676 Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice. In this study, we imaged T8I virions by cryo-electron tomography and showed that T8I mutants, like MI-treated virions, contain an immature CA-SP1 lattice. 2016 Journal of virology Abstract HIV T8I;T8I 25;81 28;84 SP1;Capsid 142;139 145;141 26537676 Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice. These included a Thr-to-Ile substitution at SP1 residue 8 (T8I), which results in impaired CA-SP1 processing. 2016 Journal of virology Abstract HIV T8I 59 62 SP1;SP1;Capsid 44;94;91 47;97;93 26537676 Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice. These results have important implications for the mechanism of action of HIV-1 MIs; they also suggest that T8I may provide a valuable tool for structural definition of the CA-SP1 boundary region, which has thus far been refractory to high-resolution analysis, apparently because of conformational flexibility in this region of Gag. 2016 Journal of virology Abstract HIV T8I 107 110 SP1;Gag;Capsid 175;327;172 178;330;174 26537676 Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice. Thus, the T8I mutation phenocopies PF-46396 treatment in terms of its ability to rescue the replication defect imposed by the MHR mutations and to impede CA-SP1 processing. 2016 Journal of virology Abstract HIV T8I 10 13 SP1;Capsid 157;154 160;156 26537676 Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice. We previously found that T8I, a mutation in SP1, rescues a PF-46396-dependent CA mutant and blocks CA-SP1 cleavage. 2016 Journal of virology Abstract HIV T8I 25 28 SP1;SP1;Capsid;Capsid 44;102;78;99 47;105;80;101 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. 2015 BioMed research international Abstract HIV I54V;I84V;L76V;L90M;M46I;M46L;V82A 48;60;76;54;36;66;42 52;64;80;58;40;70;46 PR 12 20 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). 2015 BioMed research international Abstract HIV K130N;M184V 82;64 87;69 RT 32 53 26546669 Deep analysis of HIV-1 natural variability across HIV-1 variants at residues associated with integrase inhibitor (INI) resistance in INI-naive individuals. Three secondary INI-R changes appeared with variable frequency in INI-naive individuals carrying specific HIV-1 variants: L74M in CRF43_02G (33.3%); T97A in group P (50%), J (33.3%), CRF18_cpx (20%) and F2 (11.5%); and G163RK in CRF44_BF (100%), CRF46_BF (66.7%), CRF17_BF (28.6%), F1 (21.7%), CRF12_BF (16.7%) and CRF29_BF (12.5%). 2016 The Journal of antimicrobial chemotherapy Abstract HIV G163K;G163R;L74M;T97A 219;219;122;149 225;225;126;153 IN;IN 16;66 19;69 26553990 Dynamic allostery governs cyclophilin A-HIV capsid interplay. Remarkably, the CypA loop dynamics of wild-type CA HXB2 assembly is significantly attenuated upon CypA binding, and the dynamics profiles of the A92E and G94D CypA escape mutants closely resemble that of wild-type CA assembly in complex with CypA. 2015 Proc Natl Acad Sci U S A Abstract HIV A92E;G94D 145;154 149;158 Capsid;Capsid 48;214 50;216 26553990 Dynamic allostery governs cyclophilin A-HIV capsid interplay. Through the analysis of backbone (1)H-(15)N and (1)H-(13)C dipolar tensors and peak intensities from 3D MAS NMR spectra of wild-type and the A92E and G94D CypA escape mutants, we demonstrate that assembled CA is dynamic, particularly in loop regions. 2015 Proc Natl Acad Sci U S A Abstract HIV A92E;G94D 141;150 145;154 Matrix;Capsid 104;206 106;208 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. M184V and K103N were the most frequent ADR mutations. 2015 PloS one Abstract HIV K103N;M184V 10;0 15;5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. The most prevalent PDR mutations were M46IL (1.4%), T215 revertants (0.5%), and K103NS (5.5%). 2015 PloS one Abstract HIV K103N;K103S;M46I;M46L 80;80;38;38 86;86;43;43 26559830 Four Amino Acid Changes in HIV-2 Protease Confer Class-Wide Sensitivity to Protease Inhibitors. Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. 2016 Journal of virology Abstract HIV I32V;M76L;V47I 31;47;37 35;51;41 PI 102 104 26559830 Four Amino Acid Changes in HIV-2 Protease Confer Class-Wide Sensitivity to Protease Inhibitors. We constructed HIV-2ROD9 molecular clones encoding the corresponding wild-type HIV-1 amino acids (I32V, V47I, M76L, and I82V) either individually or together (clone PRDelta4) and compared the phenotypic sensitivities (50% effective concentration [EC50]) of mutant and wild-type viruses to nine FDA-approved PI. 2016 Journal of virology Abstract HIV I32V;I82V;M76L;V47I 98;120;110;104 102;124;114;108 PI 307 309 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A) to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs)-naive IDUs. 2015 PloS one Abstract HIV A421V;C316N;C445F;I482L;V494A;V499A 60;53;67;74;81;92 65;58;72;79;86;97 Pol 107 117 26563240 Selection of Rilpivirine-Resistant HIV-1 in a Seroconverter From the SSAT 040 Trial Who Received the 300-mg Dose of Long-Acting Rilpivirine (TMC278LA). Infection with wild-type HIV-1 was confirmed on day 84 after TMC278LA injection, and the K101E mutation was detected on day 115. 2016 The Journal of infectious diseases Abstract HIV K101E 89 94 26563240 Selection of Rilpivirine-Resistant HIV-1 in a Seroconverter From the SSAT 040 Trial Who Received the 300-mg Dose of Long-Acting Rilpivirine (TMC278LA). Plasma-derived HIV-1 clones containing K101E had 4-fold increased resistance to RPV and 4-8-fold increased cross-resistance to etravirine, nevirapine, and efavirenz compared with wild type HIV-1 plasma-derived clones from the same individual. 2016 The Journal of infectious diseases Abstract HIV K101E 39 44 26566057 Efficacy and safety of a switch to rilpivirine-based regimens in treatment-experienced HIV-1-infected patients: a cohort study. Sixteen (6%) patients experienced virological failure, which was associated with the presence of the M184V/I resistance mutation in prior genotypes (P=0.02) and the use of a non-NNRTI as third agent before the switch (P=0.03). 2016 Antiviral therapy Abstract HIV M184I;M184V 101;101 108;108 NNRTI 178 183 26566161 Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study. Baseline minority etravirine RAMs (n) were detected in 8/40 VFs (V90I [2], A98G [1], L100I [1], V106I [1], E138G [1] and Y181C [2]) and 5/38 responders (V90I [3], A98G [1], V106I [1] and E138G [1]). 2016 Antiviral therapy Abstract HIV A98G;A98G;E138G;E138G;L100I;V106I;V106I;V90I;V90I;Y181C 75;163;107;187;85;96;173;65;153;121 79;167;112;192;90;101;178;70;158;126 26566161 Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study. RESULTS: By week 48, 41/101 (40.6%) patients experienced VF; 17/41 (41.5%) VFs and 22/54 (40.8%) responders had >=1 baseline etravirine RAM by PS, mainly A98G, K101E, V106I and G190A. 2016 Antiviral therapy Abstract HIV A98G;G190A;K101E;V106I 154;177;160;167 158;182;165;172 26566161 Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study. The most frequent emerging non-nucleoside reverse transcriptase inhibitor RAMs detected by PS (>=3 VFs; n) were the etravirine RAMs Y181C (8), V90I (3), L100I (3) and E138A (3). 2016 Antiviral therapy Abstract HIV E138A;L100I;V90I;Y181C 167;153;143;132 172;158;147;137 NNRTI 27 63 26568566 Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial). Only one strategy-related genotypic mutation (M184I) was detected. 2016 The Journal of antimicrobial chemotherapy Abstract HIV M184I 46 51 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. Among those genotyped, 50 % had major Protease Inhibitor mutation (M46I commonest) however 87.5 % were still susceptible to darunavir. 2015 BMC infectious diseases Abstract HIV M46I 67 72 PR 38 46 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. All viruses containing RT-M184V were resistant to FTC (>1,000-fold). 2016 Antimicrobial agents and chemotherapy Abstract HIV M184V 26 31 RT 23 25 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. As a follow-up, the in vitro characteristics of mutant HIV-1 containing RT-K65R and/or RT-M184V with IN-Q148R or IN-N155H were also evaluated, alone and in combination, for potential interactions. 2016 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V;N155H;Q148R 75;90;116;104 79;95;121;109 IN;IN;RT;RT 101;113;72;87 103;115;74;89 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. In clinical trials of coformulated elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF), emergent drug resistance predominantly involved the FTC resistance substitution M184V/I in reverse transcriptase (RT), with or without the tenofovir (TFV) resistance substitution K65R, accompanied by a primary EVG resistance substitution (E92Q, N155H, or Q148R) in integrase (IN). 2016 Antimicrobial agents and chemotherapy Abstract HIV E92Q;K65R;M184I;M184V;N155H;Q148R 375;315;216;216;381;391 379;319;223;223;386;396 RT;IN;IN;RT 227;401;412;250 248;410;414;252 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. Mutants with RT-K65R had reduced susceptibility to TFV (3.3- to 3.6-fold). 2016 Antimicrobial agents and chemotherapy Abstract HIV K65R 16 20 RT 13 15 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. Viruses with IN-Q148R or IN-N155H exhibited reduced susceptibility to EVG (137- and 40-fold, respectively) that was not affected by the addition of RT-M184V or RT-K65R/M184V. 2016 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V;M184V;N155H;Q148R 163;168;151;28;16 167;173;156;33;21 IN;IN;RT;RT 13;25;148;160 15;27;150;162 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. We previously reported that the RT-K65R, RT-M184V, and IN-E92Q substitutions lacked cross-class phenotypic resistance and replicative fitness compensation. 2016 Antimicrobial agents and chemotherapy Abstract HIV E92Q;K65R;M184V 58;35;44 62;39;49 IN;RT;RT 55;32;41 57;34;43 26574015 Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions. Without drugs present, the viral fitness of RT and/or IN mutants was diminished relative to that of the wild type in the following genotypic order: wild type > RT-M184V >= IN-N155H IN-Q148R >= RT-M184V + IN-N155H >= RT-M184V + IN-Q148R >= RT-K65R/M184V + IN-Q148R RT-K65R/M184V + IN-N155H. 2016 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;M184V;M184V;M184V;M184V;M184V;N155H;N155H;N155H;Q148R;Q148R;Q148R 242;267;163;196;219;247;272;175;207;283;184;230;258 246;271;168;201;224;252;277;180;212;288;189;235;263 IN;IN;IN;IN;IN;IN;IN;RT;RT;RT;RT;RT;RT 54;172;181;204;227;255;280;44;160;193;216;239;264 56;174;183;206;229;257;282;46;162;195;218;241;266 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. According to the phenotypic resistance performed by recombinant virus strains, VirusT215Y/V179E/Y181C/H221Y exhibited high levels of resistance to EFV (5.57-fold), and T215Y/V179E-containing virus increased 20.20-fold in AZT resistance (p < 0.01). 2015 Virology journal Abstract HIV H221Y;T215Y;V179E;V215Y;Y181C;T215Y;V179E 102;84;90;84;96;168;174 107;89;95;89;101;173;179 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. As for VirusT215Y/K103N/Y181C, only the IC50 of EFV was significantly increased. 2015 Virology journal Abstract HIV K103N;T215Y;V215Y;Y181C 18;12;12;24 23;17;17;29 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. T215Y/K103N resulted in a 26.36-fold increase in EFV (p < 0.01). 2015 Virology journal Abstract HIV K103N;T215Y 6;0 11;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. T215Y/K103N/H221Y significantly increased the resistance to AZT and 3TC. 2015 Virology journal Abstract HIV H221Y;K103N;H221Y;T215Y 13;6;12;0 18;11;17;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. The IC50 for VirusT215Y/V179E/H221Y was similar to that for VirusT215Y/V179E/Y181C. 2015 Virology journal Abstract HIV H221Y;T215Y;T215Y;V179E;V179E;V215Y;V215Y;Y181C 30;18;65;24;71;18;65;77 35;23;70;29;76;23;70;82 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. The IC50 of EFV with T215Y/V179E was lower than with T215Y/K103N (F = 93.10, P < 0.0001). 2015 Virology journal Abstract HIV K103N;T215Y;T215Y;V179E 59;21;53;27 64;26;58;32 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. VirusT215Y/K103N/Y181C/H221Y induced a dramatic IC50 increase of all the four agents (Efavirenz EFV, Zidovudine AZT, Lamivudine 3TC, and Stavudine d4T) (p < 0.01). 2015 Virology journal Abstract HIV H221Y;K103N;T215Y;V215Y;Y181C 24;11;5;5;17 29;16;10;10;22 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. VirusT215Y/V179E/Y181C increased markedly in EFV resistance (p < 0.01). 2015 Virology journal Abstract HIV T215Y;V179E;V215Y;Y181C 5;11;5;17 10;16;10;22 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. With T215Y/K103N, neither H221Y nor Y181C showed a significant increase in EFV resistance, but the interaction between 181 and 221 was statistically significant (F = 38.12, P = 0.0003). 2015 Virology journal Abstract HIV H221Y;K103N;T215Y;Y181C 26;11;5;36 31;16;10;41 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. With T215Y/V179E, Y181C significantly increase in EFV resistance, while the interaction between 181 and 221 in EFV was not statistically significant (F = 1.20, P = 0.3052). 2015 Virology journal Abstract HIV T215Y;V179E;Y181C 5;11;18 10;16;23 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. RESULTS: Fewer patients with the M184V mutation reached immunologic failure criteria than those without: 51 of 151(34%) vs. 2016 Tropical medicine & international health Abstract HIV M184V 33 38 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. The CD4 count decline among patients with the M184V mutation was 2.5 cells/mm(3) /year, whereas in those without M184V it was 14 cells/mm(3) /year (P = 0.1), but the difference in CD4 count decline with and without NNRTI resistance was marginal. 2016 Tropical medicine & international health Abstract HIV M184V;M184V 46;113 51;118 NNRTI 215 220 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. We investigated the association of M184V and NNRTI resistance with WHO immunological failure criteria and CD4 count trends, using chi-square tests and linear mixed models. 2016 Tropical medicine & international health Abstract HIV M184V 35 40 NNRTI 45 50 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. Finally, it was indicated that a water-mediated hydrogen bond between saquinavir and Asp29 in the active site (wild-type, A71V, G73S) facilitates a proper placement of the drug into the binding cavity that favors binding. 2013 Journal of chemical theory and computation Abstract HIV A71V;G73S 122;128 126;132 Asp 85 88 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. In this work, we examine L10I, G48V, L63P, A71V, G73S, V82A, and I84V single mutant HIV-1 PR strains in complexes with saquinavir to elucidate drug-protease interactions and dynamics. 2013 Journal of chemical theory and computation Abstract HIV A71V;G48V;G73S;I84V;L10I;L63P;V82A 43;31;49;65;25;37;55 47;35;53;69;29;41;59 PR;PR 148;90 156;92 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. It was shown that mutations conferring major resistance (G48V, L63P, I84V) did not present these interactions. 2013 Journal of chemical theory and computation Abstract HIV G48V;I84V;L63P 57;69;63 61;73;67 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. It was shown that mutations, which increase the flexibility of the flaps (G48V, L63P, L10I) diminish binding. 2013 Journal of chemical theory and computation Abstract HIV G48V;L10I;L63P 74;86;80 78;90;84 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. Mutants lacking this interaction (G48V, V82A, I84V) demonstrated reduced binding affinities. 2013 Journal of chemical theory and computation Abstract HIV G48V;I84V;V82A 34;46;40 38;50;44 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. The G48V mutation induces structural changes to the protease that reflect upon the drug's binding affinity, as shown by MM-PBSA and thermodynamic integration (TI) calculations (DeltaDeltaGTI = 0.3 kcal/mol; DeltaDeltaGMM-PBSA = 1.2 kcal/mol). 2013 Journal of chemical theory and computation Abstract HIV G48V 4 8 PR 52 60 26587633 A Comparative Molecular Dynamics, MM-PBSA and Thermodynamic Integration Study of Saquinavir Complexes with Wild-Type HIV-1 PR and L10I, G48V, L63P, A71V, G73S, V82A and I84V Single Mutants. The preservation of hydrogen bonds of saquinavir with both the active site and flap residues in the wild-type and certain single mutants (A71V, V82A) is also crucial for effective inhibition. 2013 Journal of chemical theory and computation Abstract HIV A71V;V82A 138;144 142;148 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. Additional neutralization experiments indicate that 882376 is not active against mutant pseudoviruses carrying the amino acid substitutions S375H and S375Y located in the 'Phe43 cavity' which is the major site of CD4 binding, suggesting that this compound may interfere with the interaction between gp120 and CD4. 2015 Bioorganic & medicinal chemistry Abstract HIV S375H;S375Y 140;150 145;155 gp120 299 304 26602836 Short Communication: Population-Based Surveillance of HIV-1 Drug Resistance in Cameroonian Adults Initiating Antiretroviral Therapy According to the World Health Organization Guidelines. Level of DRMs was low (3.77%) versus moderate (7.55%), respectively, following the WHO list (T69D, K103N) versus Stanford HIVdb (T69D, A98G, K103N, K238T), respectively. 2016 AIDS research and human retroviruses Abstract HIV A98G;K103N;K103N;K238T;T69D;T69D 135;99;141;148;93;129 139;104;146;153;97;133 26607225 Genetic determinants of Nef-mediated CD4 and HLA class I down-regulation differences between HIV-1 subtypes B and C. CONCLUSIONS: Our data suggest that these subtype-specific differences may partly contribute to inter-subtype functional differences, and identification of an immune escape mutation - S88G - that impairs Nef function is of relevance to vaccine design. 2015 Virology journal Abstract HIV S88G 183 187 Nef 203 206 26607225 Genetic determinants of Nef-mediated CD4 and HLA class I down-regulation differences between HIV-1 subtypes B and C. Subtype C consensus 20I and subtype B consensus 20M reduced and increased HLA-I down-regulation respectively, and the S88G immune escape mutation (which is significantly more frequent in subtype C than subtype B) reduced CD4 and HLA-I down-regulation. 2015 Virology journal Abstract HIV S88G 118 122 26610114 Study of the Conformational Dynamics of the Catalytic Loop of WT and G140A/G149A HIV-1 Integrase Core Domain Using Reversible Digitally Filtered Molecular Dynamics. In this study, the enhanced sampling technique, Reversible Digitally Filtered Molecular Dynamics (RDFMD), has been applied to the catalytic domain of the WT and G140A/G149A HIV-1 IN enzymes and has highlighted significant differences between the behavior of the catalytic loop which may explain the decrease of activity observed in experimental studies for this mutant. 2009 Journal of chemical theory and computation Abstract HIV G140A;G149A 161;167 166;172 IN 179 181 26613568 Binding Free Energy Calculations of Nine FDA-approved Protease Inhibitors Against HIV-1 Subtype C I36T upward arrowT Containing 100 Amino Acids Per Monomer. In this work, have investigated the binding affinities of nine FDA-approved protease inhibitor drugs against a new HIV-1 subtype C mutated protease, I36T T. 2016 Chemical biology & drug design Abstract HIV I36T 149 153 PR;PR 76;139 84;147 26613568 Binding Free Energy Calculations of Nine FDA-approved Protease Inhibitors Against HIV-1 Subtype C I36T upward arrowT Containing 100 Amino Acids Per Monomer. This and the inhibitor models were employed to generate the inhibitor/I36T T complexes, with the relative positions of the inhibitors being superimposed and aligned using the X-ray crystal structures of the inhibitors/HIV-1 subtype B complexes as a reference. 2016 Chemical biology & drug design Abstract HIV I36T 70 74 26613568 Binding Free Energy Calculations of Nine FDA-approved Protease Inhibitors Against HIV-1 Subtype C I36T upward arrowT Containing 100 Amino Acids Per Monomer. When compared to the binding free energies of the HIV-1 subtype B and subtype C proteases (calculated previously by our group using the same method), it was clear that the I36T T proteases mutations and insertion had a significant negative effect on the binding energies of the non-pepditic inhibitors nelfinavir, darunavir and tipranavir. 2016 Chemical biology & drug design Abstract HIV I36T 172 176 PR;PR 80;179 89;188 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. A single amino acid mutation, W252A, within the thumb domain impaired co-IP between eEF1A and RT, and also significantly reduced the efficiency of late reverse transcription and virus replication when incorporated into infectious HIV-1. 2015 PLoS pathogens Abstract HIV W252A 30 35 RT;RT 152;94 173;96 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Interestingly, HIV-1 with a W252A RT mutation was resistant to didemnin B negative effects showing that didemnin B affects HIV-1 by targeting the RT-eEF1A interaction. 2015 PLoS pathogens Abstract HIV W252A 28 33 RT;RT 34;146 36;148 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. Moreover, the DDE-catalytic motif (D64G/D116G/E152 K) and signature HHCC zinc-binding motifs at codon 12, 16, 40 and 43 were found to be highly conserved. 2015 Journal of translational medicine Abstract HIV D64G;D116G 34;40 39;45 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. Neither major resistance-associated IN mutations (T66I/A/K, E92Q/G, T97A, Y143HCR, S147G, Q148H/R/K, and N155H) nor silent mutations known to change the genetic barrier were observed. 2015 Journal of translational medicine Abstract HIV E92G;E92Q;N155H;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;T97A;Y143C;Y143H;Y143R 60;60;105;90;90;90;83;50;50;50;68;74;74;74 66;66;110;99;99;99;88;58;58;58;72;81;81;81 IN 36 38 26626694 Computing the Amino Acid Specificity of Fluctuations in Biomolecular Systems. We apply the new method to HIV-1 protease in its wild-type form and to a V82F-I84V mutant that shows resistance to protease inhibitors. 2006 Journal of chemical theory and computation Abstract HIV I84V;V82F 78;73 82;77 PR;PR 33;115 41;123 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. I54M, L90M double mutation resulted in a significant reduction in the susceptibility to most of the inhibitors with the exception of tipranavir. 2015 Viruses Abstract HIV L90M;I54M 6;0 10;4 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. Moreover, the treatment-associated resistance mutations (I54M, L90M) were introduced into the modular system, and comparative inhibition assays were performed to determine their effect on the susceptibility of the protease. 2015 Viruses Abstract HIV I54M;L90M 57;63 61;67 PR 214 222 26641303 Molecular Dynamics Simulations of HIV-1 Protease Suggest Different Mechanisms Contributing to Drug Resistance. A decreased interaction energy between protease and Nelfinavir was observed for the D30N mutant giving a plausible explanation for resistance, while the N88S mutation did not significantly affect the interaction energies in the bound form. 2005 Journal of chemical theory and computation Abstract HIV D30N;N88S 84;153 88;157 PR 39 47 26641303 Molecular Dynamics Simulations of HIV-1 Protease Suggest Different Mechanisms Contributing to Drug Resistance. In particular, Asp30 forms more frequently a hydrogen bond with Ser88 in the unbound N88S mutant thus interfering with the Asp30-Nelfinavir interaction. 2005 Journal of chemical theory and computation Abstract HIV N88S 85 89 Asp;Asp 15;123 18;126 26641303 Molecular Dynamics Simulations of HIV-1 Protease Suggest Different Mechanisms Contributing to Drug Resistance. In the present work molecular dynamics simulations of an active-site mutation (D30N) and a nonactive-site mutation (N88S) of HIV-1 protease that both directly confer resistance to the protease inhibitor Nelfinavir but not to Amprenavir were performed and compared to wild-type HIV-protease. 2005 Journal of chemical theory and computation Abstract HIV D30N;N88S 79;116 83;120 PR;PR;PR 131;184;281 139;192;289 26641303 Molecular Dynamics Simulations of HIV-1 Protease Suggest Different Mechanisms Contributing to Drug Resistance. Structural analysis including both ligand-bound and unliganded HIV-1 proteases revealed that the free N88S mutant protease shows significant differences in its hydrogen bonding pattern compared to free or Nelfinavir-bound wild-type protease. 2005 Journal of chemical theory and computation Abstract HIV N88S 102 106 PR;PR;PR 69;114;232 78;122;240 26641303 Molecular Dynamics Simulations of HIV-1 Protease Suggest Different Mechanisms Contributing to Drug Resistance. These findings suggest that different molecular mechanisms contribute to resistance in active-site and nonactive-site mutants and propose a mechanism for the N88S mutant that is based on a shift of the conformational equilibrium of the unbound protease. 2005 Journal of chemical theory and computation Abstract HIV N88S 158 162 PR 244 252 26650686 An in-silico approach aimed to clarify the role of Y181C and K103N HIV-1 reverse transcriptase mutations versus Indole Aryl Sulphones. The effects of two of the most clinically relevant RT mutations (Y181C; K103N) were studied by a computational approach. 2016 Journal of molecular graphics & modelling Abstract HIV K103N;Y181C 72;65 77;70 RT 51 53 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Subtype C- and F1-infected patients displayed the highest levels of reduced viral susceptibility at baseline, respectively 13.2% and 9.3%, mainly due to subtype- and geographic-dependent occurrence of RPV-RAMs E138A and A98G as natural polymorphisms. 2016 AIDS research and human retroviruses Abstract HIV A98G;E138A 220;210 224;215 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. 2015 BMC bioinformatics Abstract HIV K20T;L33F;V77I 120;111;49 124;115;53 PR 70 72 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. RESULTS: Two HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. 2015 BMC bioinformatics Abstract HIV K20T;L33F;L33F;V77I;V77I 146;103;151;96;139 150;107;155;102;145 PR;PR;PR 83;126;17 91;134;19 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. 2015 BMC bioinformatics Abstract HIV V77I 0 4 PR 88 96 26700639 Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 2015 PloS one Abstract HIV K65R;M184I;M184V;Y181C 126;49;49;64 130;56;56;69 26700639 Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda. The high rate of K65R and TAMs could compromise second line regimens including NRTIs. 2015 PloS one Abstract HIV K65R 17 21 NRTI 79 84 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. Protease substitutions I13V, E35D, M36I, R57K, H69K, and L89M, which serve as drug-resistance support mutations in subtype B, were present in the majority of subtype-A1 sequences of the population. 2015 HIV/AIDS (Auckland, N.Z.) Abstract HIV E35D;H69K;I13V;L89M;M36I;R57K 29;47;23;57;35;41 33;51;27;61;39;45 PR 0 8 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. 2015 PloS one Abstract HIV G190A;K103N;K65R;M184V;V106M;Y181C 170;156;112;102;181;163 175;161;116;108;186;168 NRTI;NNRTI;NRTI 35;133;79 67;138;83 26719253 MxB Is Not Responsible for the Blocking of HIV-1 Infection Observed in Alpha Interferon-Treated Cells. Here we showed that the reason why MxB does not block HIV-1-G208R is that MxB does not interact with HIV-1 cores bearing the mutation G208R. 2015 Journal of virology Abstract HIV G208R;G208R 134;60 139;65 26719253 MxB Is Not Responsible for the Blocking of HIV-1 Infection Observed in Alpha Interferon-Treated Cells. To understand this contribution, we used HIV-1 bearing the G208R capsid mutant (HIV-1-G208R), which overcomes the restriction imposed by cells expressing MxB. 2015 Journal of virology Abstract HIV G208R;G208R 59;86 64;91 Capsid 65 71 26719253 MxB Is Not Responsible for the Blocking of HIV-1 Infection Observed in Alpha Interferon-Treated Cells. To understand whether MxB contributes to the HIV-1 restriction imposed by IFN-alpha-treated human cells, we challenged IFN-alpha-treated cells with HIV-G208R and found that MxB does not contribute to the restriction imposed by IFN-alpha-treated cells. 2015 Journal of virology Abstract HIV G208R 152 157 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Although escape mutation K165R was genotypically stable in plasma, it rapidly reverted to wildtype Gag KP9 in both CSF and in microglia cultures. 2016 Journal of neurovirology Abstract HIV K165R 25 30 Gag 99 102 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Insertion of gag K165R into the neurovirulent clone SIV/17E-Fr reduced viral replication in vitro compared to SIV/17E-Fr. 2016 Journal of neurovirology Abstract HIV K165R 17 22 Gag 13 16 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Using a simian immunodeficiency virus (SIV)/macaque model, we examined CNS outcomes in pigtailed macaques expressing the MHC class I allele Mane-A1*084:01 which confers resistance to SIV-induced CNS disease and induces the prototypic viral escape mutation Gag K165R. 2016 Journal of neurovirology Abstract HIV K165R 260 265 Gag 256 259 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. We also found lower cerebrospinal fluid (CSF), but not plasma, viral loads in macaques inoculated with SIV/17E-Fr K165R versus those inoculated with wildtype. 2016 Journal of neurovirology Abstract HIV K165R 114 119 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. In all four cases, K65R, K70E and M184IV were not detected prior to seroconversion, suggesting PrEP-related resistance was selected and not transmitted. 2016 AIDS (London, England) Abstract HIV K65R;K70E;M184I;M184V 19;25;34;34 23;29;40;40 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. We previously reported that PrEP-related mutations (K65R, K70E or M184IV) were detected by 454 sequencing following seroconversion in nine individuals who acquired HIV during the Partners PrEP Study. 2016 AIDS (London, England) Abstract HIV K65R;K70E;M184I;M184V 52;58;66;66 56;62;72;72 26746222 Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD). A specific focus was put on the prevalence of the tenofovir disoproxil fumarate (TDF) signature mutation K65R in HIV-1 RT in relation to the application of TDF within ART. 2016 Medical microbiology and immunology Abstract HIV K65R 105 109 RT 119 121 26746222 Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD). The prevalence of K65R decreased from 2.6 % in 2005 to 0.2 % in 2012 despite increased use of TDF-containing ART. 2016 Medical microbiology and immunology Abstract HIV K65R 18 22 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. 2016 PloS one Abstract HIV G190A;K103N;M184V;Y181C 72;47;61;54 77;52;66;59 26761642 Systematic review to determine the prevalence of transmitted drug resistance mutations to rilpivirine in HIV-infected treatment-naive persons. Pooled results from the Stanford database (n=52,680) correlated with these findings indicating a low prevalence of 8/9 rilpivirine mutations (<0.1%), except for E138A/G/K/Q/R (2.9%, 95% CI 1.8, 4.4). 2016 Antiviral therapy Abstract HIV E138A;E138G;E138K;E138Q;E138R 161;161;161;161;161 174;174;174;174;174 26761642 Systematic review to determine the prevalence of transmitted drug resistance mutations to rilpivirine in HIV-infected treatment-naive persons. Rilpivirine mutations assessed were: L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L. 2016 Antiviral therapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;L100I;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 53;53;53;53;53;100;93;44;44;37;110;110;68;75;75;75;86 66;66;66;66;66;105;98;51;51;42;117;117;73;84;84;84;91 26761642 Systematic review to determine the prevalence of transmitted drug resistance mutations to rilpivirine in HIV-infected treatment-naive persons. The prevalence of E138A/G/K/Q/R mutations is higher (0.7%) and varies according to geographical region and HIV subtype. 2016 Antiviral therapy Abstract HIV E138A;E138G;E138K;E138Q;E138R 18;18;18;18;18 31;31;31;31;31 26761642 Systematic review to determine the prevalence of transmitted drug resistance mutations to rilpivirine in HIV-infected treatment-naive persons. Two mutations were more prevalent: E138A/G/K/Q/R (0.7%, 95% CI 0.2, 1.3) and Y181C/I/V (0.3%, 95% CI 0.2, 0.4). 2016 Antiviral therapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;Y181C;Y181I;Y181V 35;35;35;35;35;77;77;77 48;48;48;48;48;86;86;86 26795727 Novel mutant human immunodeficiency virus type 1 strains with high degree of resistance to cynomolgus macaque TRIMCyp generated by random mutagenesis. Analysis of these mutants revealed that V86A and G116E mutations in the capsid region conferred partial resistance to CM TRIM5alpha without substantial fitness cost when propagated in MT4 cells expressing CM TRIM5alpha. 2016 The Journal of general virology Abstract HIV G116E;V86A 49;40 54;44 Capsid 72 78 26795727 Novel mutant human immunodeficiency virus type 1 strains with high degree of resistance to cynomolgus macaque TRIMCyp generated by random mutagenesis. CM TRIMCyp-resistant viruses were obtained after three rounds of selection in MT4 cells expressing CM TRIMCyp and these were found to contain four amino acid substitutions (H87R, A88G, P90D and P93A) in L4/5. 2016 The Journal of general virology Abstract HIV A88G;H87R;P90D;P93A 179;173;185;194 183;177;189;198 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Enzymatic studies showed that RMNC6 interferes with efavirenz (an approved NNRTI) in its binding to the RT polymerase domain, although NNRTI resistance-associated mutations such as K103N, Y181C and Y188L had a minor impact on RT susceptibility to RMNC6. 2016 PloS one Abstract HIV K103N;Y181C;Y188L 181;188;198 186;193;203 Pol;NNRTI;NNRTI;RT;RT 107;75;135;104;226 117;80;140;106;228 26802545 Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives targeting the entrance channel of NNRTI binding pocket. In particular, the inhibition of IIb against the K103N mutation (EC50 = 49 nM), which confers resistance to a wide variety of NNRTIs, was about 140 times more effective than NVP (EC50 = 6.78 muM), 50 times more than DLV (EC50 = 2.48 muM) and about 3 times more than EFV (EC50 = 0.12 muM), indicating that the newly designed compounds have great potential to be further developed as new anti-HIV-1 agents. 2016 European journal of medicinal chemistry Abstract HIV K103N 49 54 NNRTI 126 132 26803719 Withdrawing inactive NRTIs in HIV-1 subjects with suppressed viraemia: a randomized trial. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine-associated mutations was 3 (IQR: 0-4). 2016 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 51;51 58;58 26804933 Discovery of the Aryl-phospho-indole IDX899, a Highly Potent Anti-HIV Non-nucleoside Reverse Transcriptase Inhibitor. Optimization of the phosphinate aryl substituent led to the discovery of the 3-Me,5-acrylonitrile-phenyl analogue RP-13s (IDX899) having an EC50 of 11 nM against the Y181C/K103N double mutant. 2016 Journal of medicinal chemistry Abstract HIV K103N;Y181C 172;166 177;171 26804933 Discovery of the Aryl-phospho-indole IDX899, a Highly Potent Anti-HIV Non-nucleoside Reverse Transcriptase Inhibitor. Since a major problem associated with NNRTI treatment is the emergence of drug resistant virus, this work focused on optimization of the APhI against clinically relevant HIV-1 Y181C and K103N mutants and the Y181C/K103N double mutant. 2016 Journal of medicinal chemistry Abstract HIV K103N;K103N;Y181C 214;186;208 219;191;213 NNRTI 38 43 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. Sanger sequencing missed the K65R mutation in 30% of samples. 2016 AIDS (London, England) Abstract HIV K65R 29 33 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. By multiple stepwise logistic regression, factors associated with undetectable HIV RNA after 6 months of ART were: having M184V/I (odds ratio [OR] 0.11; 95% confidence interval [CI] 0.02-0.62, p = 0.013), condom use (OR 2.38; 95% CI 1.12-5.06, p = 0.024), and adherence per 5% increase (OR 1.16; 95% CI 1.00-1.35, p = 0.044). 2016 PloS one Abstract HIV M184I;M184V 122;122 129;129 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. Fourteen major mutations of codon 99-191 on the RT gene were selected (K103N, V106A/M, V108I, Q151M, Y181C/I, M184V/I, Y188C/L/H, and G190S/A) at a cost of testing of 35 USD. 2016 PloS one Abstract HIV G190A;G190S;K103N;M184I;M184V;Q151M;V106A;V106M;V108I;Y181C;Y181I;Y188C;Y188H;Y188L 134;134;71;110;110;94;78;78;87;101;101;119;119;119 141;141;76;117;117;99;85;85;92;108;108;128;128;128 RT 48 50 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. The prevalence of each HIVDR mutation were K103N 6.0%, V106I 1.1%, V108I 0.4%, Y181C 2.3%, Y181I 0.7%, Y181V 0.4%, M184V 3.0%, M184I 1.5%, and G190A 2.3%. 2016 PloS one Abstract HIV G190A;K103N;M184I;M184V;V106I;V108I;Y181C;Y181I;Y181V 143;43;127;115;55;67;79;91;103 148;48;132;120;60;72;84;96;108 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. 2016 The Lancet. Infectious diseases Abstract HIV M184I;M184V 90;90 98;98 NNRTI 129 134 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. 2016 The Lancet. Infectious diseases Abstract HIV K65N;K65R;K70E;K70G;K70Q 69;69;79;79;79 75;75;87;87;87 RT;RT 105;128 126;130 26833003 [Analysis of HIV-1 drug resistance among 1 922 individuals experiencing virological failure of first-line antiretroviral therapy in Henan province]. K103N/S was the most commonly emerged NNRTI resistance mutation (34.32% (659)). 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV K103N;K103S 0;0 7;7 NNRTI 38 43 26833003 [Analysis of HIV-1 drug resistance among 1 922 individuals experiencing virological failure of first-line antiretroviral therapy in Henan province]. K65R/N and Q151M complex existed in 23 and 4 patients, respectively. 2015 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV K65N;K65R;Q151M 0;0;11 6;6;16 26833152 Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations. DOR also displayed higher IQs than those of RPV and EFV against other prevalent NNRTI-associated mutants, with the exception of Y188L. 2016 Antimicrobial agents and chemotherapy Abstract HIV Y188L 128 133 NNRTI 80 85 26833152 Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations. DOR displayed IQs of 39, 27, and 25 against the K103N, Y181C, and K103N/Y181C mutants, respectively. 2016 Antimicrobial agents and chemotherapy Abstract HIV K103N;K103N;Y181C;Y181C 48;66;72;55 53;71;77;60 26833152 Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations. DOR exhibits potent antiviral activity against wild-type virus and K103N, Y181C, and K103N/Y181C mutant viruses, with 50% inhibitory concentrations (IC50s) of 12, 21, 31, and 33 nM, respectively, when measured in 100% normal human serum (NHS). 2016 Antimicrobial agents and chemotherapy Abstract HIV K103N;K103N;Y181C;Y181C 67;85;91;74 72;90;96;79 26833152 Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations. No viral breakthrough was observed with DOR, whereas breakthrough viruses were readily detected with RPV and EFV against Y181C and K103N viruses, respectively. 2016 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 131;121 136;126 26833152 Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations. Resistance selections were conducted with K103N, Y181C, G190A, and K103N/Y181C mutants at clinically relevant concentrations of DOR, RPV, and EFV. 2016 Antimicrobial agents and chemotherapy Abstract HIV G190A;K103N;K103N;Y181C;Y181C 56;42;67;73;49 61;47;72;78;54 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. A derivative was created, additionally harboring the TAM K70R and the reversions M151Q as well as R65K since K65R antagonizes excision. 2016 Nucleic acids research Abstract HIV K65R;K70R;M151Q;R65K 109;57;81;98 113;61;86;102 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Although MR-RT harbored the most significant amino acid exchanges T215Y and Q151M of each pathway, it exclusively used AZTTP discrimination, indicating that the two mechanisms are mutually exclusive and that the Q151M pathway is obviously preferred since it confers resistance to most nucleoside inhibitors. 2016 Nucleic acids research Abstract HIV Q151M;Q151M;T215Y 76;212;66 81;217;71 RT 12 14 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In addition, K65R, known to antagonize AZTMP excision in HIV-1 subtype B was present. 2016 Nucleic acids research Abstract HIV K65R 13 17 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. MR-R65K-K70R-M151Q was competent of AZTMP excision, whereas other combinations thereof with only one or two exchanges still promoted discrimination. 2016 Nucleic acids research Abstract HIV K70R;M151Q;R65K 8;13;3 12;18;7 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. We analyzed a multi-drug resistant (MR) HIV-1 reverse transcriptase (RT), subcloned from a patient-derived subtype CRF02_AG, harboring 45 amino acid exchanges, amongst them four thymidine analog mutations (TAMs) relevant for high-level AZT (azidothymidine) resistance by AZTMP excision (M41L, D67N, T215Y, K219E) as well as four substitutions of the AZTTP discrimination pathway (A62V, V75I, F116Y and Q151M). 2016 Nucleic acids research Abstract HIV A62V;D67N;F116Y;K219E;M41L;Q151M;T215Y;V75I 380;293;392;306;287;402;299;386 384;297;397;311;291;407;304;390 RT;RT 46;69 67;71 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. To elucidate this mechanism, we determined the crystal structure of the ligand-free state of a protease with high-level DRV resistance and six DRV resistance-associated mutations (including I47V and I50V), which we generated by in vitro selection. 2016 Frontiers in microbiology Abstract HIV I47V;I50V 190;199 194;203 PR 95 103 26876929 Novel indole sulfides as potent HIV-1 NNRTIs. In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. 2016 Bioorganic & medicinal chemistry letters Abstract HIV K103N 149 154 NNRTI 66 72 26896929 High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo. Direct virus competition assays demonstrated a rank order of wild-type>K65R>V148I mutants in terms of viral fitness. 2016 Virology Abstract HIV K65R;V148I 71;76 75;81 26896929 High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo. In contrast, SIVmac239-Q151N was replication incompetent in vitro and in pigtailed macaques. 2016 Virology Abstract HIV Q151N 23 28 26896929 High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo. In single round in vitro-replication assays, SIVmac239-K65R demonstrated significantly higher fidelity than wild-type, and rapidly reverted to wild-type following infection of macaques. 2016 Virology Abstract HIV K65R 55 59 26896929 High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo. SIVmac239-K65R and SIVmac239-V148I viruses had reduced replication capacity compared to wild-type SIVmac239. 2016 Virology Abstract HIV K65R;V148I 10;29 14;34 26896929 High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo. Thus, we showed that RT mutants, and specifically the common K65R drug-resistance mutation, had impaired replication capacity and higher fidelity. 2016 Virology Abstract HIV K65R 61 65 RT 21 23 26896929 High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo. We investigated the effect of RT mutations K65R, Q151N and V148I on SIV replication and fidelity in vitro, along with SIV replication in pigtailed macaques. 2016 Virology Abstract HIV K65R;Q151N;V148I 43;49;59 47;54;64 RT 30 32 26899538 Time to Viremia for Patients Taking their First Antiretroviral Regimen and the Subsequent Resistance Profiles. One new NNRTI (Y181C) mutation was identified and three patients taking PI-based regimens developed NRTI mutations (M184 V, M184I, and T215Y). 2016 HIV clinical trials Abstract HIV M184I;M184V;T215Y;Y181C 124;116;135;15 129;122;140;20 NNRTI;NRTI;PI 8;100;72 13;104;74 26899540 Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. 2016 HIV clinical trials Abstract HIV E138A;E138G;E138K;E138Q;H221Y;Y181C 56;56;56;56;80;69 67;67;67;67;85;74 26899540 Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. 2016 HIV clinical trials Abstract HIV K103N 23 28 26899540 Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. 2016 HIV clinical trials Abstract HIV M184I;Y181C;Y181Y 42;30;30 47;37;37 26911541 Efficacy and safety of antiretroviral regimens including raltegravir to treat HIV-infected patients with hemophilia. A pattern of resistance to raltegravir was evident, including the primary mutation N155H and the secondary mutation T97A. 2016 Bioscience trends Abstract HIV N155H;T97A 83;116 88;120 26912618 APOBEC3G and APOBEC3F Act in Concert To Extinguish HIV-1 Replication. In the exceptional case, JRCSFvifH42/43D replicated after a prolonged delay with no mutations in vif but instead a V27I mutation in the RNase H coding sequence. 2016 Journal of virology Abstract HIV V27I 115 119 Vif 97 100 26912618 APOBEC3G and APOBEC3F Act in Concert To Extinguish HIV-1 Replication. Unexpectedly, fixation of mutations that replaced H42/43D or W79S in viral RNA lagged behind the appearance of high viral loads. 2016 Journal of virology Abstract HIV W79S 61 65 26917227 Purification and characterization of naturally occurring HIV-1 (South African subtype C) protease mutants from inclusion bodies. In SDS-PAGE, we obtained these HIV proteases as single bands of approximately 11.5, 11.6 and 11.7 kDa for the wild type, I36T Tand L38L N L mutants, respectively. 2016 Protein expression and purification Abstract HIV I36T;L38L 121;131 125;135 PR 35 44 26917227 Purification and characterization of naturally occurring HIV-1 (South African subtype C) protease mutants from inclusion bodies. The enzyme was recovered efficiently (0.25 mg protein/L of Escherichia coli culture) and had high specific activity of 2.02, 2.20 and 1.33 mumol min(-1) mg(-1) at an optimal pH of 5 and temperature of 37C for the wild type, I36T T and L38L N L, respectively. 2016 Protein expression and purification Abstract HIV I36T;L38L 224;235 228;239 26917227 Purification and characterization of naturally occurring HIV-1 (South African subtype C) protease mutants from inclusion bodies. Using recombinant DNA technology, we constructed three recombinant plasmids in pGEX-6P-1 and expressed them containing a sequence encoding wild type HIV protease and two mutants (I36T T contains 100 amino acids and L38L N L contains 101 amino acids). 2016 Protein expression and purification Abstract HIV I36T;L38L 179;215 184;219 PR 153 161 26921800 Transmission dynamics of HIV-1 subtype B in the Basque Country, Spain. The most prevalent mutations for each inhibitor class were PI L90M, NRTI T215D/Y/F, and NNRTI K103N, which were also among the most prevalent resistant variants in the whole dataset. 2016 Infection, genetics and evolution Abstract HIV K103N;L90M;T215D;T215F;T215Y 94;62;73;73;73 99;66;82;82;82 NNRTI;NRTI;PI 88;68;59 93;72;61 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. For example, some mutations, such as V82A, had no effect on IC50, but reduced the slope. 2016 PloS one Abstract HIV V82A 37 41 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. BACKGROUND: K65R is a relatively rare drug resistance mutation (DRM) selected by the NRTIs tenofovir, didanosine, abacavir and stavudine and confers cross-resistance to all NRTIs except zidovudine. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 12 16 NRTI;NRTI 85;173 90;178 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. CONCLUSIONS: A high rate of K65R emergence may suggest that ingesting low doses of lamivudine via breast milk could select for this mutation. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 28 32 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. Factors associated with K65R emergence were assessed using Fisher's exact test and the Wilcoxon rank-sum test. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 24 28 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. Infants with K65R had low baseline CD4 cell counts (P = 0.014), were more likely to have DRMs earlier (<=6 weeks versus >=14 weeks, P = 0.007) and were more likely to have multiclass drug resistance (P = 0.035). 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 13 17 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. K65R emerged in half of the infants by 6 weeks and in the rest by 14 weeks of age. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 0 4 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. K65R had reverted by 3 months after cessation of breastfeeding. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 0 4 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. M184V was the most common mutation associated with K65R emergence. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184V 51;0 55;5 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. None of the mothers at delivery or the infants with a positive genotype at first time of positivity had the K65R mutation. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 108 112 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. OBJECTIVES: In this study we investigated the frequency of emergence of the K65R mutation and factors associated with it in HIV-1-infected infants exposed to low doses of maternal lamivudine, zidovudine and either nevirapine or nelfinavir ingested through breast milk, using specimens collected from the Kisumu Breastfeeding Study. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 76 80 HIV infections 124 138 26953333 Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk. RESULTS: K65R was detected in samples from 6 of the 24 infants (25%) who acquired HIV-1 infection by the age of 6 months. 2016 The Journal of antimicrobial chemotherapy Abstract HIV K65R 9 13 HIV infections 82 97 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Here, we combine genetic and immunological analyses to identify A*24:02-positive individuals likely to have been infected with Y135F-containing HIV-1. 2016 PloS one Abstract HIV Y135F 127 132 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Japan's population features limited HLA diversity which is driving population-level HIV adaptation: for example, >60% of Japanese express HLA-A*24:02 and its associated Nef-Y135F escape mutation represents the population consensus. 2016 PloS one Abstract HIV Y135F 173 178 Nef 169 172 2695931 Recombinant HIV1 protease secreted by Saccharomyces cerevisiae correctly processes myristylated gag polyprotein. A D25E active site variant of the retroviral enzyme exhibited diminished autocatalytic activity when expressed intracellularly or secreted from yeast. 1989 Proteins Abstract HIV D25E 2 6 26972300 Single Active Site Mutation Causes Serious Resistance of HIV Reverse Transcriptase to Lamivudine: Insight from Multiple Molecular Dynamics Simulations. Molecular dynamics simulations, binding free energy calculations, principle component analysis (PCA), and residue interaction network analysis were employed in order to investigate the molecular mechanism of M184I single mutation which played pivotal role in making the HIV-1 reverse transcriptase (RT) totally resistant to lamivudine. 2016 Cell biochemistry and biophysics Abstract HIV M184I 208 213 RT;RT 276;299 297;301 26977119 A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients. In fact, the structural variant of the IL4RA I50V, previously shown to result in enhanced signal transduction, was significantly associated with greater cavity size, and a variant of IL13RA2 was associated with disease in females. 2016 Mediators of inflammation Abstract HIV I50V 45 49 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. However, the hardening effect of disulfide crosslinking (A204C and A14C/E45C) is lower than that of hydrophobic interactions (E45A and E45A/R132T). 2016 Retrovirology Abstract HIV A14C;A204C;E45A;E45A;E45C;R132T 67;57;126;135;72;140 71;62;131;139;76;145 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. We find that hyperstable CA mutant assemblies (A204C, A14C/E45C, E45A and E45A/R132T) are significantly stiffer than WT assemblies. 2016 Retrovirology Abstract HIV A14C;A204C;E45A;E45A;E45C;R132T 54;47;65;74;59;79 58;52;69;78;63;84 Capsid 25 27 26990626 Sensitive sentinel mutation screening reveals differential underestimation of transmitted HIV drug resistance among demographic groups. One-third of K65R was in persons who also had at least one of the other mutations screened. 2016 AIDS (London, England) Abstract HIV K65R 13 17 26990626 Sensitive sentinel mutation screening reveals differential underestimation of transmitted HIV drug resistance among demographic groups. Sensitive screening identified 72% more TDR than conventional sequencing for the five mutations assessed (13.6 vs. 7.9%, P < 0.0001), with K65R having the greatest increase (0-1.7%). 2016 AIDS (London, England) Abstract HIV K65R 139 143 26994843 Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket. Among them, compound 15b was identified as the most potent inhibitor with EC50 values of 0.11 muM and 2.18 muM against wt and K103N/Y181C double mutant HIV-1 strain (RES056), respectively. 2016 European journal of medicinal chemistry Abstract HIV K103N;Y181C 126;132 131;137 26997611 Functional characteristics of the natural polymorphisms of HIV-1 gp41 in HIV-1 isolates from enfuvirtide-naive Korean patients. Moreover, most point mutants showed lower IC50 values for enfuvirtide than the wild type, whereas the L7M substitution resulted in a slightly increased IC50 value. 2016 Archives of virology Abstract HIV L7M 102 105 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. The nonnucleoside reverse transcriptase inhibitor mutation, K103N, was the most common mutation, occurring in 27 (3.8%) of the participants, while nucleoside reverse transcriptase inhibitor (NRTI) SDRMs were detected in 10 (1.4%) of the participants, of whom eight had only a single NRTI SDRM. 2016 AIDS research and human retroviruses Abstract HIV K103N 60 65 NNRTI;NRTI;NRTI;NRTI 4;147;191;283 39;179;195;287 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Infectious molecular HIV-1 clones containing Q148N alone and in combination with G140S demonstrated ~2.4-4.5 reduced elvitegravir susceptibility depending on the virus's genetic context but retained susceptibility to raltegravir and dolutegravir. 2016 AIDS research and human retroviruses Abstract HIV G140S;Q148N 81;45 86;50 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Q148N was associated with a higher replication capacity than Q148H, suggesting that this mutation may be more fit in the absence of selective INSTI therapy. 2016 AIDS research and human retroviruses Abstract HIV Q148H;Q148N 61;0 66;5 INSTI 142 147 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. The integrase strand transfer inhibitor (INSTI)-resistance mutations Q148H/K/R are arguably the most important INSTI-resistance mutations as they represented the first step to high-level dolutegravir cross-resistance. 2016 AIDS research and human retroviruses Abstract HIV Q148H;Q148K;Q148R 69;69;69 78;78;78 IN;INSTI;INSTI 4;41;111 13;46;116 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. This level of reduced elvitegravir susceptibility is lower than that observed with Q148H/K/R and in fact the infected individual responded to an initial treatment regimen containing tenofovir/emtricitabine/elvitegravir/cobicistat. 2016 AIDS research and human retroviruses Abstract HIV Q148H;Q148K;Q148R 83;83;83 92;92;92 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. We describe an individual with transmitted four-class drug resistance whose virus sequence had the previously uncharacterized mutation Q148N. 2016 AIDS research and human retroviruses Abstract HIV Q148N 135 140 27009513 Genotypic Characterization of Human Immunodeficiency Virus Type 1 Derived from Antiretroviral Therapy-Naive Individuals Residing in Sorong, West Papua. Major drug resistance-associated mutations for PR inhibitors were not detected; however, mutations for the RT inhibitors, A62V and E138A, appeared in a few samples, indicating the possible emergence of transmitted HIV-1 drug resistance in Sorong, West Papua. 2016 AIDS research and human retroviruses Abstract HIV A62V;E138A 122;131 126;136 PR;RT 47;107 49;109 27017055 HIV-1 adaptation to low levels of CCR5 results in V3 and V2 loop changes that increase envelope pathogenicity, CCR5 affinity and decrease susceptibility to Maraviroc. Analysis of subtype B sequences showed that N302Y is over-represented in CXCR4 tropic viruses in comparison to CCR5 tropic isolates. 2016 Virology Abstract HIV N302Y 44 49 27017055 HIV-1 adaptation to low levels of CCR5 results in V3 and V2 loop changes that increase envelope pathogenicity, CCR5 affinity and decrease susceptibility to Maraviroc. HIV-1 adaptation in a T cell line expressing low levels of CCR5 resulted in two specific mutations; N302Y and E172K. 2016 Virology Abstract HIV E172K;N302Y 110;100 115;105 27017055 HIV-1 adaptation to low levels of CCR5 results in V3 and V2 loop changes that increase envelope pathogenicity, CCR5 affinity and decrease susceptibility to Maraviroc. The N302Y mutation led to accelerated virus replication, increase in Maraviroc IC50 and an increase in Envelope mediated bystander apoptosis in low CCR5 expressing cells. 2016 Virology Abstract HIV N302Y 4 9 Env 103 111 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. Cell culture selections and phenotypic drug susceptibility assays assessed resistance via the G118R pathway. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G118R 94 99 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. Cell culture selections were used to assess the in vitro progression of the G118R pathway leading to cross-resistance to all integrase inhibitors. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G118R 76 81 IN 125 134 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. CONCLUSIONS: Although resistance to dolutegravir is typically rare, genetic polymorphisms and monotherapy can facilitate the acquisition of G118R. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G118R 140 145 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. In this study, rapid development of the G118R mutation arose following a switch from first-line elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine to dolutegravir monotherapy. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G118R 40 45 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. The appearance of G118R in these two cases and subtype C and CRF02_AG in vitro selections were related to a rare GGA natural polymorphism at codon 118 (1.5% prevalence), facilitating a GGA to AGA transition. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G118R 18 23 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. The G118R mutation also arose in a treatment-experienced patient switched to dolutegravir monotherapy. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G118R 4 9 27029845 Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. The genetic basis for G118R selection and potential phenotypic outcome was ascertained. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G118R 22 27 27031256 Lamivudine Monotherapy: Experience of Medium-term Outcomes in HIV-infected Children Unable to Adhere to Triple Therapy. By preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is occasionally used while awaiting patient readiness for second- or third-line therapy, but this strategy has not been widely studied. 2016 The Pediatric infectious disease journal Abstract HIV M184V 32 37 27033350 Prevalence of Drug Resistance Associated Mutations Among the Anti Retroviral Therapy Exposed HIV-1 Infected Individuals in Manipur, Northeast India. Predominant DRAMs at RT genes were M184V, T215Y, M41L and V108I and H221Y while at PR genes were M46I and I47V. 2016 Current HIV research Abstract HIV H221Y;I47V;M184V;M41L;M46I;T215Y;V108I 68;106;35;49;97;42;58 73;110;40;53;101;47;63 PR;RT 83;21 85;23 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Three of five mutations in PR(S17) correlating with major drug resistance, M46L, G48V, and V82S, and five of 11 natural variations differ from the mutations in two clinically derived extreme mutants, PR20 and PR22 bearing 19 and 22 mutations, respectively. 2016 Biochemistry Abstract HIV G48V;M46L;V82S 81;75;91 85;79;95 PR;PR;PR 200;209;27 202;211;29 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. Antiretroviral-naive adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. 2016 AIDS (London, England) Abstract HIV G190A;K103N;K65R;M184V;Y181C 142;128;160;149;135 147;133;164;154;140 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. Resistance to tenofovir (K65R) was found in 2014 but not in 2006. 2016 AIDS (London, England) Abstract HIV K65R 25 29 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. L228I in combination with Y188C displayed a high level of cross-resistance to both nevirapine (NVP) and efavirenz (EFV). 2016 AIDS research and human retroviruses Abstract HIV Y188C;L228I 26;0 31;5 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. Modeling study suggested that the copresence of Y188C/L228I or A139V/Y232H might induce conformational changes to RT, which might result in reduced drug susceptibility and viral RC due to abolished hydrogen bonding or complex interaction with vicinal residues. 2016 AIDS research and human retroviruses Abstract HIV A139V;L228I;Y188C;Y232H 63;54;48;69 68;59;53;74 RT 114 116 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. Mutations Y188C/L228I, A139V, Y232H, and A139V/Y232H reduced more than 55% of viral RC compared with that of the wild-type (WT) reference virus. 2016 AIDS research and human retroviruses Abstract HIV A139V;A139V;L228I;Y188C;Y232H;Y232H 23;41;16;10;47;30 28;46;21;15;52;35 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. Our results demonstrated that L228I and Y232H were novel accessory nonnucleoside reverse transcriptase inhibitor resistance-related mutations and provided valuable information for clinicians to design more effective treatment to patients infected with HIV-1 subtype CRF08_BC. 2016 AIDS research and human retroviruses Abstract HIV L228I;Y232H 30;40 35;45 NNRTI 67 102 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. Results showed that the novel mutation, L228I, conferred a low-level resistance to etravirine by itself. 2016 AIDS research and human retroviruses Abstract HIV L228I 40 45 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. The copresence of A139V and Y232H induced a moderate level of resistance to NVP and EFV. 2016 AIDS research and human retroviruses Abstract HIV A139V;Y232H 18;28 23;33 27067022 Novel Mutations L228I and Y232H Cause Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Combinational Pattern. To characterize two novel mutations L228I and Y232H in the primer grip of reverse transcriptase (RT) of HIV-1 circulating recombination form 08_BC (CRF08_BC) subtype, both mutant clones were constructed to determine their impacts on viral phenotypic susceptibility and replication capacity (RC). 2016 AIDS research and human retroviruses Abstract HIV L228I;Y232H 36;46 41;51 RT;RT 74;97 95;99 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Compounds 6a, 14c, and 14d showed high potency against the 1b-resistant E138K mutated viral strain as well as good balance between anti-HIV-1 activity and desirable druglike properties. 2016 Journal of medicinal chemistry Abstract HIV E138K 72 77 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. From the perspective of optimizing future NNRTI compounds as clinical trial candidates, computational modeling results provided valuable information about how the R(1) group might provide greater efficacy against the E138K mutant. 2016 Journal of medicinal chemistry Abstract HIV E138K 217 222 NNRTI 42 47 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Three series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new-generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b). 2016 Journal of medicinal chemistry Abstract HIV E138K 154 159 NNRTI 239 275 27074792 An unusual case of underlying rilpivirine resistance in an antiretroviral-naive man with AIDS. His case illustrates the growing importance of archived resistance mutations including the less common E138A mutation, as well as the risk and rapid occurrence of IRIS in AIDS patients initiated on integrase inhibitors. 2016 International journal of STD & AIDS Abstract HIV E138A 103 108 IN 198 207 AIDS 171 175 27074792 An unusual case of underlying rilpivirine resistance in an antiretroviral-naive man with AIDS. We report an antiretroviral treatment (ART)-naive patient with acquired immunodeficiency syndrome (AIDS) (CD4 cell count 20 cells/mm3, viral load 8439 copies/mL), who was infected with HIV-1 sub-type B virus containing a reverse transcriptase mutation, E138A, associated with rilpivirine resistance. 2016 International journal of STD & AIDS Abstract HIV E138A 253 258 RT 221 242 AIDS;AIDS 63;99 97;103 27075671 Resolution of Specific Nucleotide Mismatches by Wild-Type and AZT-Resistant Reverse Transcriptases during HIV-1 Replication. Outcomes for wild-type (WT) RT and an AZT-resistant (AZT(R)) RT containing a thymidine analog mutation set-D67N, K70R, D215F, and K219Q-were compared. 2016 Journal of molecular biology Abstract HIV D215F;D67N;K219Q;K70R 119;107;130;113 124;111;135;117 RT;RT 28;61 30;63 27076106 HIV virological failure and drug resistance in a cohort of Tanzanian HIV-infected adults. Drug resistance mutations were present in 87/115 samples (75.7%); the most common were M184V/I (52.2%) and K103N (35%). 2016 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M184I;M184V 107;87;87 112;94;94 27076656 Deep Sequencing of HIV-1 RNA and DNA in Newly Diagnosed Patients with Baseline Drug Resistance Showed No Indications for Hidden Resistance and Is Biased by Strong Interference of Hypermutation. Despite focused selection of patients with T215 revertants or singleton mutations, deep sequencing failed to identify the resistant T215Y/F or M184V or any other resistance mutation, indicating that in most of these cases there is no hidden resistance and that the virus detected at diagnosis by population sequencing is the original infecting variant. 2016 Journal of clinical microbiology Abstract HIV M184V;T215F;T215Y 143;132;132 148;139;139 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. Although R263K is the most common resistance substitution for the INSTI dolutegravir, an INSTI treatment-experienced individual recently failed dolutegravir-based therapy, with E157Q being the only resistance-associated change reported. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;R263K 177;9 182;14 INSTI;INSTI 66;89 71;94 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. Because Glu157 is thought to lie within the binding site of HIV IN DNA binding inhibitors such as FZ41, we also evaluated DNA binding activity and resistance to IN inhibitors in the presence of E157Q. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 194 199 IN;IN 64;161 66;163 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. CONCLUSIONS: This study shows that E157Q may act as a compensatory mutation for R263K. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;R263K 35;80 40;85 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. Given that different resistance pathways can sometimes synergize to confer high levels of resistance to antiretroviral drugs, we studied the effects of E157Q in association with R263K. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;R263K 152;178 157;183 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. OBJECTIVES: The E157Q substitution in HIV-1 integrase (IN) is a relatively common natural polymorphism associated with HIV resistance to IN strand transfer inhibitors (INSTIs). 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 16 21 IN;INSTI;IN;IN 44;168;55;137 53;174;57;139 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. RESULTS: E157Q alone had little if any effect on the biochemical activity of IN, and partially restored the activity of R263K-containing IN. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;R263K 9;120 14;125 IN;IN 77;137 79;139 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. Since E157Q is a natural polymorphism present in 1%-10% of HIV-positive individuals, it may be of particular importance for patients receiving INSTI therapy. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 6 11 INSTI 143 148 27084918 Polymorphic substitution E157Q in HIV-1 integrase increases R263K-mediated dolutegravir resistance and decreases DNA binding activity. The E157Q/R263K double viral mutant displayed infectiousness in culture equivalent to WT, while increasing resistance to dolutegravir by 10-fold compared with lower-level resistance associated with R263K alone. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;R263K;R263K 4;10;198 9;15;203 27090171 Identification and Characterization of BMS-955176, a Second-Generation HIV-1 Maturation Inhibitor with Improved Potency, Antiviral Spectrum, and Gag Polymorphic Coverage. MI potency was optimized using a panel of engineered reporter viruses containing site-directed polymorphic changes in Gag that reduce susceptibility to bevirimat (including V362I, V370A/M/Delta, and T371A/Delta), leading incrementally to the identification of BMS-955176. 2016 Antimicrobial agents and chemotherapy Abstract HIV T371A;T371Delta;V362I;V370A;V370Delta;V370M 199;199;173;180;180;180 210;210;178;193;193;193 Gag 118 121 27092410 The design of 8-hydroxyquinoline tetracyclic lactams as HIV-1 integrase strand transfer inhibitors. This manuscript describes a number of 8-hydroxyquinoline tetracyclic lactams with exceptional antiviral activity against HIV-1 and little loss of potency against the IN signature resistance mutations Q148K and G140S/Q148H. 2016 European journal of medicinal chemistry Abstract HIV G140S;Q148H;Q148K 210;216;200 215;221;205 IN 166 168 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. In terms of loci, the detection rate of the alleles was greater than 97% for M41L, K65R, M184V and G190A, 91.2% for K101E/Q/P, 91.2% for T215F/Y, 89.9% for K103N/S and 80.5% for L210W. 2016 PloS one Abstract HIV G190A;K101E;K101P;K101Q;K103N;K103S;K65R;L210W;M184V;M41L;T215F;T215Y 99;116;116;116;156;156;83;178;89;77;137;137 104;125;125;125;163;163;87;183;94;81;144;144 27107820 HIV-1 capsid is involved in post-nuclear entry steps. A105S and N74D capsid mutant viruses did not accumulate capsid in the nucleus, irrespective of C-A1 treatment. 2016 Retrovirology Abstract HIV N74D;A105S 10;0 14;5 Capsid;Capsid 15;56 21;62 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. The non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K103N and P225H were more prevalent in both ARV drug-naive and ARV drug-experienced subjects. 2016 PloS one Abstract HIV K103N;P225H 69;79 74;84 NNRTI;NNRTI 52;4 57;40 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. The nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V was more frequent in ARV drug-experienced individuals, while T215YFrev and M41L were more frequent in ARV drug-naive subjects. 2016 PloS one Abstract HIV M184V 63 68 NRTI;NRTI 48;4 52;36 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. The nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V was more frequent in ARV drug-experienced individuals, while T215YFrev and M41L were more frequent in ARV drug-na茂ve subjects. 2016 PloS one Abstract HIV M41L;T215Y 144;130 148;139 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. K103N was the most common EFV-associated RAM (56.5% vs. 2016 PloS one Abstract HIV K103N 0 5 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Y181C was the most common NVP-associated RAM (54.3% vs. 2016 PloS one Abstract HIV Y181C 0 5 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. However, with the exception of E138K, our data suggest that the mutations that reduce the potency of DOR and RPV are non-overlapping. 2016 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138K 31 36 27125365 Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%). 2016 HIV clinical trials Abstract HIV E157Q;F121Y;Q148R;Y143R 172;148;162;155 177;153;167;160 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Although rare, emerging resistance against DTG is often associated with the R263K substitution in integrase. 2016 Retrovirology Abstract HIV R263K 76 81 IN 98 107 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Given the reduced fitness of RTI-resistant viruses, we investigated potential impacts on viral replication of combining R263K and H51Y/R263K with major RTI-resistance substitutions including K65R, L74V, K103N, E138K, and M184I/V. 2016 Retrovirology Abstract HIV E138K;H51Y;K103N;K65R;L74V;M184I;M184V;R263K;R263K 210;130;203;191;197;221;221;135;120 215;134;208;195;201;228;228;140;125 RT;RT 29;152 32;155 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. H51Y/R263K plus a RT mutation, and moderately reduced in double mutants. 2016 Retrovirology Abstract HIV R263K;H51Y 5;0 10;4 RT 18 20 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In-vitro-selected R263K was associated with impaired viral replication capacity, DNA integration, and integrase strand-transfer activity, especially when accompanied by the secondary mutation H51Y. 2016 Retrovirology Abstract HIV H51Y;R263K 192;18 196;23 IN 102 111 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. R263K plus a RT mutation, compared to wild-type and single RT-mutant viruses. 2016 Retrovirology Abstract HIV R263K 0 5 RT;RT 13;59 15;61 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. RESULTS: We combined the R263K or H51Y/R263K with RTI-resistance mutations into the proviral plasmid pNL4.3 and measured the resulting viral infectiousness, replication capacity, and ability to integrate viral DNA into host cells. 2016 Retrovirology Abstract HIV H51Y;R263K;R263K 34;39;25 38;44;30 RT 50 53 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. At Raltegravir failure, N155H was detected in four patients, and other secondary mutations were detected in five patients (71.4 %). 2016 BMC infectious diseases Abstract HIV N155H 24 29 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. CONCLUSION: This is a pilot study that demonstrates the possibility of properly identifying N155H and some secondary mutations 29-53 months after failure. 2016 BMC infectious diseases Abstract HIV N155H 92 97 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. In proviral DNA, N155H was detected by population sequencing in three patients (42.8 %), and UDS demonstrated a 9.77 % relative abundance of N155H in the remaining patient. 2016 BMC infectious diseases Abstract HIV N155H;N155H 17;141 22;146 27181553 CD8 Encephalitis Caused by Persistently Detectable Drug-resistant HIV. Drug resistant testing of the serum and the cerebrospinal fluid (CSF) both demonstrated a M184V mutation. 2016 Internal medicine (Tokyo, Japan) Abstract HIV M184V 90 95 27188354 [The prevalence of primary HIV-1 drug resistance in newly reported HIV infections in Henan]. M184V/I(2.08%)and K103N/S(2.88%)were the most commonly emerged NRTI and NNRTI resistance mutation. 2016 Zhonghua liu xing bing xue za zhi Abstract HIV K103N;K103S;M184I;M184V 18;18;0;0 25;25;7;7 NNRTI;NRTI 72;63 77;67 27208653 High resistance barrier to tenofovir alafenamide is driven by higher loading of tenofovir diphosphate into target cells compared to tenofovir disoproxil fumarate. Using a newly developed virus breakthrough assay with TAF exposure set at physiological concentrations, we show that HIV-1 clinical isolates harboring TFV resistance mutations such as K65R, 3 or 4 thymidine-analog mutations (TAMs), Q151M/K65R, or T69 insertion complex could be inhibited by TAF, but not by TFV when used at clinically relevant concentrations for TDF. 2016 Antiviral research Abstract HIV K65R;K65R;Q151M 184;238;232 188;242;237 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. 2016 Journal of the International AIDS Society Abstract HIV K65R 14 18 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. 2016 Journal of the International AIDS Society Abstract HIV K65R 29 33 27231280 Usefulness of an HIV DNA resistance genotypic test in patients who are candidates for a switch to the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination. Rilpivirine/emtricitabine/tenofovir disoproxil fumarate RAMs studied were K65R, L100I, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C and M230I/L in the RT. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;K65R;L100I;M184I;M184V;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 96;96;96;96;96;152;145;87;87;74;80;129;129;162;162;111;118;118;118;138 109;109;109;109;109;157;150;94;94;78;85;136;136;169;169;116;127;127;127;143 RT 177 179 27235396 The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7. K71me is important for full Tat transactivation, as KMT7 knockdown impaired the transcriptional activity of wild type (WT) Tat but not a Tat K71R mutant. 2016 The Journal of biological chemistry Abstract HIV K71R 141 145 Tat;Tat;Tat 28;123;137 31;126;140 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The binding affinity of Ala82 in V82A decreases relative to Val82 in WT. 2016 International journal of molecular sciences Abstract HIV V82A 33 37 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The drug resistance of D30N can be attributed to the decline in binding affinity of residues 28 and 29. 2016 International journal of molecular sciences Abstract HIV D30N 23 27 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The stable hydrophobic core, including the side chain of Ile54 in the wild type (WT) complex, became unstable in I54M because the side chain of Met54 is flexible with two alternative conformations. 2016 International journal of molecular sciences Abstract HIV I54M 113 117 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. To elucidate the molecular mechanism of drug resistance associated with mutations (D30N, I50V, I54M, and V82A) and inhibitor (GRL-0519) complexes, we have performed five molecular dynamics (MD) simulations and calculated the binding free energies using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. 2016 International journal of molecular sciences Abstract HIV D30N;I50V;I54M;V82A 83;89;95;105 87;93;99;109 27241734 Distinctive Drug-resistant Mutation Profiles and Interpretations of HIV-1 Proviral DNA Revealed by Deep Sequencing in Reverse Transcriptase. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher's exact test, P<0.05). 2016 Biomedical and environmental sciences Abstract HIV M184I;M230I 14;24 19;29 27267005 Structural optimization of pyridine-type DAPY derivatives to exploit the tolerant regions of the NNRTI binding pocket. Additionally, compounds I-8c2 and I-8c3 showed moderate activity against NNRTI resistant strains baring mutations K103N and Y181C with EC50 values of 6.2 muM and 6.8 muM, respectively. 2016 European journal of medicinal chemistry Abstract HIV K103N;Y181C 114;124 119;129 NNRTI 73 78 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. As expected, CypA depletion had no additional effect on the behavior of the P90A mutant but modestly increased the IFN-alpha sensitivity of wild-type virus. 2016 Journal of virology Abstract HIV P90A 76 80 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Interestingly, the infectivity of wild-type or P90A virus could be rescued from the MX2-independent IFN-alpha-induced blocks in THP-1 cells by treatment with cyclosporine (Cs) or its nonimmunosuppressive analogue SDZ-NIM811, indicating that Cs-sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-alpha-induced blocks. 2016 Journal of virology Abstract HIV P90A 47 51 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. We show here that the HIV-1 CA mutations N74D and A105T, both of which allow escape from inhibition by MX2 and the truncated version of cleavage and polyadenylation specific factor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A, all increase sensitivity to IFN-alpha-mediated inhibition. 2016 Journal of virology Abstract HIV A105T;N74D;P90A 50;41;250 55;45;254 Capsid 28 30 27279617 Changes in HIV-1 Capsid Stability Induced by Common Cytotoxic-T-Lymphocyte-Driven Viral Sequence Mutations. The described compensatory mutations L268M and S173A observed in R264K viruses reconstituted the capsid-uncoating half-time. 2016 Journal of virology Abstract HIV L268M;R264K;S173A 37;65;47 42;70;52 Capsid 97 103 27279617 Changes in HIV-1 Capsid Stability Induced by Common Cytotoxic-T-Lymphocyte-Driven Viral Sequence Mutations. The frequently occurring HLA-B57- and HLA-B27-associated CTL escape mutations T242N and R264K resulted in delayed capsid uncoating, suggesting modulation of capsid stability. 2016 Journal of virology Abstract HIV R264K;T242N 88;78 93;83 Capsid;Capsid 114;157 120;163 27294305 Rilpivirine as a Treatment for HIV-infected Antiretroviral-naive Adolescents: Week 48 Safety, Efficacy, Virology and Pharmacokinetics. Eight patients experienced virologic failure, including 5 who developed rilpivirine resistance-associated mutations, mostly E138K, K101E and M230L. 2016 The Pediatric infectious disease journal Abstract HIV E138K;K101E;M230L 124;131;141 129;136;146 27307565 Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected during Virus Passage In Vivo. Nonetheless, revertant viruses that restored the WT CA sequence and hence CA binding to CPSF6 emerged in three out of four A77V-infected animals. 2016 Journal of virology Abstract HIV A77V 123 127 Capsid;Capsid 52;74 54;76 27307565 Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected during Virus Passage In Vivo. Surprisingly, the A77V mutant virus maintained the ability to replicate in monocyte-derived macrophages, primary CD4(+) T cells, and humanized mice at a level comparable to that for the wild-type (WT) virus. 2016 Journal of virology Abstract HIV A77V 18 22 27307565 Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected during Virus Passage In Vivo. The A77V mutation rendered HIV-1 largely independent from TNPO3, NUP358, and NUP153 for infection and altered the integration site preference of HIV-1 without any discernible effects during the late steps of the virus life cycle. 2016 Journal of virology Abstract HIV A77V 4 8 27307565 Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected during Virus Passage In Vivo. To assess the requirement for optimal CPSF6-CA binding during infection of primary cells and in vivo, we utilized a novel CA mutation, A77V, that significantly reduced CA binding to CPSF6. 2016 Journal of virology Abstract HIV A77V 135 139 Capsid;Capsid;Capsid 44;122;168 46;124;170 27307566 Recapitulating Cross-Species Transmission of Simian Immunodeficiency Virus SIVcpz to Humans by Using Humanized BLT Mice. We also identified mutations of SIVcpzMB897 (Env G411R and G413R) and SIVcpzBF1167 (Env H280Q and Q380R) at 14 weeks postinoculation. 2016 Journal of virology Abstract HIV G411R;G413R;H280Q;Q380R 49;59;88;98 54;64;93;103 Env;Env 45;84 48;87 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected in 17 of 26 (65%) patients, 2 (7%) had Thymidine analogue mutations, and 3 (11%) had K65R. 2016 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R 164 168 NNRTI;NNRTI 0;48 36;53 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. KIF5B knockdown also prevents the nuclear entry and infection by HIV-1, but does not exert a similar effect on the N74D or P90A capsid mutants which do not rely on Nup358 for nuclear import. 2016 PLoS pathogens Abstract HIV N74D;P90A 115;123 119;127 Capsid 128 134 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. This interaction between NUP358 and the HIV-1 core is dependent on multiple capsid binding surfaces, as this association is not observed following infection with capsid mutants in which a conserved hydrophobic binding pocket (N74D) or the cyclophilin A binding loop (P90A) is disrupted. 2016 PLoS pathogens Abstract HIV N74D;P90A 226;267 230;271 Capsid;Capsid 76;162 82;168 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. An unidentified mechanism could amplify resistance to rilpivirine conferred by E138K. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K 79 84 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. Analysis of recombinant HIV-1 variants indicated that E138K conferred low-level rilpivirine resistance and that coexistence of I135T/L with E138K amplified the resistance. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K;E138K;I135L;I135T 54;140;127;127 59;145;134;134 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. CONCLUSIONS: I135T/L, escape mutations from HLA-B*51/52-restricted cytotoxic T lymphocytes, which are prevalent in Japan, may predispose HIV-1 to harbour E138K upon failure of rilpivirine-containing ART. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K;I135L;I135T 154;13;13 159;20;20 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. E138K emerged in three patients while other rilpivirine resistance mutations emerged in the other three patients. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K 0 5 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. E138K in HIV-1 reverse transcriptase (RT) is a primary mutation in resistance to rilpivirine, although in vitro experiments showed it confers only <3-fold resistance. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K 0 5 RT;RT 15;38 36;40 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. I135T/L were identified in only three patients with E138K and existed before the introduction of rilpivirine-containing ART. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K;I135L;I135T 52;0;0 57;7;7 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. OBJECTIVES: The objective of this study was to reveal the mechanism amplifying rilpivirine resistance conferred by E138K. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K 115 120 27330069 Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations. The effects of mutations commonly identified with E138K on rilpivirine susceptibility were analysed by using recombinant HIV-1 variants. 2016 The Journal of antimicrobial chemotherapy Abstract HIV E138K 50 55 27333000 Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting. Population sequencing and ultrasensitive allele-specific PCR detected the M184V mutation, but no other TDF- or FTC-associated mutations, including those present as minor variants. 2016 PloS one Abstract HIV M184V 74 79 27334566 Genotypic HIV-1 Drug Resistance Among Patients Failing Tenofovir-Based First-Line HAART in South India. Considering the nature of K65R mutation in increasing susceptibility to AZT and its low prevalence, we conclude that in most patients failing TDF-based first-line therapy, AZT can be considered for second-line therapy followed by TDF itself. 2016 AIDS research and human retroviruses Abstract HIV K65R 26 30 27334566 Genotypic HIV-1 Drug Resistance Among Patients Failing Tenofovir-Based First-Line HAART in South India. Mutational association shows, K65R was negatively associated with TAMs (OR 0.31, p .008), M184V (OR 0.14, p .57), and K70E (OR 0.29, p .02). 2016 AIDS research and human retroviruses Abstract HIV K65R;K70E;M184V 30;118;90 34;122;95 27334566 Genotypic HIV-1 Drug Resistance Among Patients Failing Tenofovir-Based First-Line HAART in South India. The predominant NRTI and NNRTI mutations observed were M184IV (59.9%), K65R (28.1%), and thymidine analogue mutations (TAMs, 29.3%) and K103NS (54.5%), V106AM (39.5%), and Y181CIV (19.8%), respectively. 2016 AIDS research and human retroviruses Abstract HIV K103N;K103S;K65R;M184I;M184V;V106A;V106M;Y181C;Y181I;Y181V 136;136;71;55;55;152;152;172;172;172 142;142;75;61;61;158;158;179;179;179 NNRTI;NRTI 25;16 30;20 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. The most frequent major mutations were K103N, M184V, T215, M41L, D67N at reverse transcriptase gene and M46, I54V and V82A at protease gene. 2016 International journal of environmental research and public health Abstract HIV D67N;I54V;K103N;M184V;M41L;V82A 65;109;39;46;59;118 69;113;44;51;63;122 RT;PR 73;126 94;134 27342546 Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa. RESULTS: At first virological failure, DRM(s) were detected in 87% of participants: K103N (38.7%), G190A (21.8%), Y181C (20.2%), V106M (8.4%), K101E (8.4%), any E138 (7.6%) and V108I (7.6%) associated with NNRTIs, and M184V (69.7%), any thymidine analogue mutation (9.2%), K65R (5.9%) and K70R (5.0%) associated with NRTIs. 2016 The Journal of antimicrobial chemotherapy Abstract HIV G190A;K101E;K103N;K65R;K70R;M184V;V106M;V108I;Y181C 99;143;84;273;289;218;129;177;114 104;148;89;277;293;223;134;182;119 NNRTI;NRTI 206;317 212;322 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). The Vpr activity depends on its N-terminal region, which was disrupted by a single A30L mutation. 2016 Virology Abstract HIV A30L 83 87 Vpr 4 7 27352730 Expansion of the E138A mutation in newly diagnosed HIV-infected patients in Gran Canaria. We studied 25 HIV newly diagnosed patients with the E138A mutation since the year 2010. 2016 Diagnostic microbiology and infectious disease Abstract HIV E138A 52 57 27353350 HIV Drug Resistance in Antiretroviral-Naive Patients in Mexico After 10 Years: Is There a Difference? In both groups, mutations in N88D protease inhibitor were identified, D67N and T69D were found for nucleoside reverse transcriptase inhibitors (NRTIs), and K103N was found for non-nucleoside reverse transcriptase inhibitors. 2016 AIDS research and human retroviruses Abstract HIV D67N;K103N;N88D;T69D 70;156;29;79 74;161;33;83 NNRTI;NRTI;PR;NRTI 176;99;34;144 212;131;42;149 27354282 SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). Furthermore, a C-terminally truncated Vpr mutant and point mutants R80A and Q65R, all of which lack G2 arrest activity, are able to down-regulate MUS81-EME1, suggesting that Vpr-induced G2 arrest is not correlated with MUS81-EME1 down-regulation. 2016 The Journal of biological chemistry Abstract HIV Q65R;R80A 76;67 80;71 Vpr;Vpr 38;174 41;177 27355415 Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia. Resistance mutations in 50 of 73 children with available genotyping at first VF included M184V (56%), >=1 thymidine analogue mutation (TAM; 40%), >=4 TAMs (10%), Q151M (4%), any major LPV mutation (8%), >=6 LPV mutations (2%), and any major ATV mutation (4%). 2016 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;Q151M 89;162 94;167 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. NNRTI TDR increase was associated mainly with K101E, K103N and G190A. 2016 PloS one Abstract HIV G190A;K101E;K103N 63;46;53 68;51;58 NNRTI 0 5 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. NRTI TDR decrease was associated mainly with M184V, K70R and T215Y. 2016 PloS one Abstract HIV K70R;M184V;T215Y 52;45;61 56;50;66 NRTI 0 4 27356854 Rapid In Vitro Evaluation of Antiretroviral Barrier to Resistance at Therapeutic Drug Levels. At high multiples of its CCE Cmin, emtricitabine (FTC) selected for the rapid emergence of M184I/V, a result consistent with resistance emergence in vivo. 2016 AIDS research and human retroviruses Abstract HIV M184I;M184V 91;91 98;98 27367488 The M184I/V and K65R nucleoside resistance mutations in HIV-1 prevent the emergence of resistance mutations against dolutegravir. DESIGN: The objective of this study was to determine the effects of the M184I/V and K65R substitutions in reverse transcriptase on the ability of HIV-1 to become resistant against RAL, EVG or DTG. 2016 AIDS (London, England) Abstract HIV K65R;M184I;M184V 84;72;72 88;79;79 RT 106 127 27367488 The M184I/V and K65R nucleoside resistance mutations in HIV-1 prevent the emergence of resistance mutations against dolutegravir. In such cases, common resistance substitutions in reverse transcriptase that were associated with nucleos(t)ide reverse transcriptase inhibitors included M184I/V and K65R and these occurred together with various mutations in integrase. 2016 AIDS (London, England) Abstract HIV K65R;M184I;M184V 166;154;154 170;161;161 IN;NRTI;RT 225;98;50 234;133;71 27367488 The M184I/V and K65R nucleoside resistance mutations in HIV-1 prevent the emergence of resistance mutations against dolutegravir. METHODS: We performed tissue culture selection experiments using reverse transcriptase inhibitor-resistant viruses containing resistance substitutions at positions K65R, M184I or M184V in the presence of increasing concentrations of RAL, EVG or DTG and monitored changes in integrase sequences by genotyping. 2016 AIDS (London, England) Abstract HIV K65R;M184I;M184V 164;170;179 168;175;184 IN;RT 274;65 283;86 27368990 Antiretroviral drug resistance mutations in naive and experienced patients in Shiraz, Iran, 2014. Among the 40 ART-naive patients, two mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance (two with Y115F and T215I) and three associated with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (two with G190S and Y181C, four with V179T) were found. 2016 Archives of virology Abstract HIV G190S;T215I;V179T;Y115F;Y181C 253;144;280;134;263 258;149;285;139;268 NNRTI;NRTI;NNRTI;NRTI 177;63;225;107 213;95;230;111 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. However, these structures give only a partial sense for the limited inhibition of the 3'-processing reaction by INSTIs and how INSTIs can be modified to overcome drug resistance, notably against the G140S-Q148H double mutation. 2016 Nucleic acids research Abstract HIV G140S;Q148H 199;205 204;210 INSTI;INSTI 112;127 118;133 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. In addition, the G140S-Q148H (SH) mutant integrase, which has a reduced 3'-processing activity, becomes more active and more resistant to inhibition of 3'-processing by RAL and DTG in the absence of the -1 and +1 bases. 2016 Nucleic acids research Abstract HIV G140S;Q148H 17;23 22;28 IN 41 50 27377073 BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial. Seven young people (SCT group, n = 2; CT group, n = 5) had major non-nucleoside reverse transcriptase inhibitor mutations at VL failure, of whom two (n = 1 SCT group, n = 1 CT group) had the M184V mutation. 2016 Health technology assessment (Winchester, England) Abstract HIV M184V 191 196 NNRTI 65 101 27381400 The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity. The R953C mutant shows a 4-fold decrease in discrimination of analog nucleotides relative to the wild type. 2016 Antimicrobial agents and chemotherapy Abstract HIV R953C 4 9 27381400 The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity. The R953C Pol-gamma mutant binding affinity for dCTP is 8-fold less than that of the wild type. 2016 Antimicrobial agents and chemotherapy Abstract HIV R953C 4 9 Pol 10 13 27381400 The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity. We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-gamma) in an HIV-infected patient with mitochondrial toxicity. 2016 Antimicrobial agents and chemotherapy Abstract HIV C2857T;R953C 24;41 30;46 Pol;Pol 51;69 61;72 HIV infections 86 98 27384653 A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability. Interestingly, poor CD4 binding of W69A could be fully restored by introducing a compensatory mutation within layer 2 (S115W). 2016 Journal of virology Abstract HIV S115W;W69A 119;35 124;39 27384653 A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability. Structural studies of HIV-1 gp120 coree W69A/S115W mutant bound to the CD4 peptide mimetic M48U1 and Fab of anti-cluster A antibody N60-i3 revealed no perturbations to the overall structure of the double mutant compared to the wild-type protein but identified higher mobility within the interface between layer 1 and layer 2, the bridging sheet region, and the CD4 binding site.IMPORTANCE HIV-1 Env transitions to the CD4-bound conformation are required for viral entry. 2016 Journal of virology Abstract HIV S115W;W69A 45;40 50;44 gp120;Env 28;395 33;398 27384665 Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. 2016 Journal of virology Abstract HIV P157S;A3T;A3V 109;97;88 114;100;91 SP1;SP1;Gag;Capsid 84;93;166;106 87;96;169;108 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. Lead compound 8 inhibited RT with submicromolar potency (IC50=0.73muM) and also maintained some activity against the clinically important RT mutants K103N and Y181C (IC50=9.2, 3.5muM) in cell-free assays. 2016 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 149;159 154;164 RT;RT 26;138 28;140 27412696 HIV-1 Genetic Diversity and Drug Resistance Mutations Among Treatment-Naive Adult Patients in Suriname. Analysis of drug resistance mutations showed only one transmitted dug resistance mutation (TDRM) (V75M) in a single strain. 2016 AIDS research and human retroviruses Abstract HIV V75M 98 102 27432606 Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients. N155H mutation was detected at failure in one patient. 2016 The Journal of antimicrobial chemotherapy Abstract HIV N155H 0 5 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Amino acid mutations in Tat functional domains included N24K (44%), N29K (58%), and N40K (30%) in CRF02_AG, and N24K in all G subtypes. 2016 Viruses Abstract HIV N24K;N24K;N29K;N40K 56;112;68;84 60;116;72;88 Tat 24 27 27453103 [Drug resistance and influencing factors in adult AIDS patients receiving antiretroviral treatment in Dehong, Yunnan province]. Most of the 82 patients were resistant to NRTIs and NNRTIs, the main mutation loci were M184V and K103N. 2016 Zhonghua liu xing bing xue za zhi Abstract HIV K103N;M184V 98;88 103;93 NNRTI;NRTI 52;42 58;47 27460519 Accumulation of HIV-1 Drug Resistance Mutations After First-Line Immunological Failure to Evaluate the Options of Recycling NRTI Drugs in Second-Line Treatment: A Study from South India. The result shows that predominant nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations were M184V/I (87.3% in FTF and 79% in STF) followed by TAMs (53.4% in FTF and 54.5% in STF). 2017 AIDS research and human retroviruses Abstract HIV M184I;M184V 102;102 109;109 NRTI;NRTI 34;81 69;85 27460548 HIV-1 Vpr increases HCV replication through VprBP in cell culture. We found that the Vpr mutant Q65R, which is deficient in VprBP binding, could not enhance HCV replication. 2016 Virus research Abstract HIV Q65R 29 33 Vpr 18 21 27473196 Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV". With respect to the effect of HIV-1 subtype diversity, analyses of HIV-1 clade C infection among South Africans revealed that clade C infection induced cognitive impairment that was independent of the substitution in HIV-1 Trans-Activator of Transcription (Tat; C31S). 2016 Journal of neurovirology Abstract HIV C31S 262 266 Tat 257 260 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. An IN's substitution, A128T, associated with viral resistance to NCINIs, decreased the NCINI-induced increase of fluorescence, suggesting that A128T reduces the potential for IN over-multimerization. 2016 Journal of virological methods Abstract HIV A128T;A128T 22;143 27;148 IN;IN 3;175 5;177 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. Moreover, E11K and F181T substitutions known to inhibit IN tetramerization also reduced the NCINI-induced fluorescence increase, suggesting that NCINI-induced IN over-multimerization was more likely to occur from tetramer subunits than from dimer subunits. 2016 Journal of virological methods Abstract HIV E11K;F181T 10;19 14;24 IN;IN 56;159 58;161 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). 2017 HIV medicine Abstract HIV K103N;L90M;M41L 40;94;78 45;98;82 27489265 Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. A large increase in the binding of CD4bs and V3-targeting antibodies is observed for the N197Q mutant in trimeric Env, while no changes are observed with monomeric gp120. 2016 Journal of virology Abstract HIV N197Q 89 94 gp120;Env 164;114 169;117 27489265 Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan. While the overall structure and thermostability are not altered, a subtle increase in the flexibility of the variable loops at the trimeric interface of adjacent protomers is evident in the N197Q mutant by hydrogen-deuterium exchange mass spectrometry. 2016 Journal of virology Abstract HIV N197Q 190 195 27501911 Arylazolyl(azinyl)thioacetanilides. Part 20: Discovery of novel purinylthioacetanilides derivatives as potent HIV-1 NNRTIs via a structure-based bioisosterism approach. In addition, LBD-6 showed moderate activity against L100I mutant (EC50=5.64muM) and double mutant strain RES056 (EC50=22.24muM). 2016 Bioorganic & medicinal chemistry Abstract HIV L100I 52 57 27512074 Novel Acylguanidine-Based Inhibitor of HIV-1. SM111-mediated inhibition of HIV-1 was partially overcome by a Vpu I17R mutation alone or a Vpu W22* truncation in combination with Env N136Y. 2016 Journal of virology Abstract HIV I17R;N136Y;W22X 67;136;96 71;141;100 Vpu;Vpu;Env 63;92;132 66;95;135 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Based on our observations, the L189F mutant capsid remains structurally and functionally unchanged and may therefore be the best candidate for use in studies aimed at better understanding the role of the protease in the early postentry events of viral infection or retrovirus-mediated gene transduction. 2016 FEBS open bio Abstract HIV L189F 31 36 PR;Capsid 204;44 212;50 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. However, the effects of other mutations (W23A, A77P, and L189P) were dramatic, as assessed by secondary structure determination or cyclophilin A-binding assay. 2016 FEBS open bio Abstract HIV A77P;L189P;W23A 47;57;41 51;62;45 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Our results indicate that while the introduced mutations changed the cleavage rate at the mutated sites of the capsid protein by HIV-1 protease, some of them caused only negligible or moderate structural changes (A78V, L189F, and L189I). 2016 FEBS open bio Abstract HIV A78V;L189F;L189I 213;219;230 217;224;235 PR;Capsid 135;111 143;117 27530391 Prevalence of integrase inhibitor resistance mutations in Austrian patients recently diagnosed with HIV from 2008 to 2013. One primary mutation was observed (F121Y) in a patient sample from 2012 leading to 5-10-fold reduced susceptibility to raltegravir and elvitegravir. 2017 Infection Abstract HIV F121Y 35 40 27530391 Prevalence of integrase inhibitor resistance mutations in Austrian patients recently diagnosed with HIV from 2008 to 2013. Two patients carried the accessory mutations E138K and G140A, respectively, where both lie on the Q148 pathway. 2017 Infection Abstract HIV E138K;G140A 45;55 50;60 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. A98S polymorphism improves virological response to TDF+FTC-containing HAART. 2016 Journal of global antimicrobial resistance Abstract HIV A98S 0 4 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. A98S was the only mutation significantly correlated with an increased proportion of patients achieving VS at 24 weeks (94.0% vs. 2016 Journal of global antimicrobial resistance Abstract HIV A98S 0 4 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. At concentrations close to the minimal concentration achieved in patient plasma, TDF and FTC exhibited higher potency in the presence of A98S-mutated virus compared with wild-type (IC90,TDF, 8.6+-1.1 vs. 2016 Journal of global antimicrobial resistance Abstract HIV A98S 137 141 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. Docking analysis showed the higher potency of TDF and FTC in the presence of A98S-mutated virus was mainly due to higher binding affinity between drugs and mutated RT compared with wild-type. 2016 Journal of global antimicrobial resistance Abstract HIV A98S 77 81 RT 164 166 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. In the presence of FTC, A98S also partially restored the RT binding affinity impaired by M184V alone. 2016 Journal of global antimicrobial resistance Abstract HIV A98S;M184V 24;89 28;94 RT 57 59 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. The efficacy of FTC, abrogated by M184V, was partially restored by A98S (IC90,FTC, 5169+-5931nM for A98S+M184V vs. 2016 Journal of global antimicrobial resistance Abstract HIV A98S;A98S;M184V;M184V 67;100;34;105 71;104;39;110 27530997 The HIV-1 reverse transcriptase polymorphism A98S improves the response to tenofovir disoproxil fumarate+emtricitabine-containing HAART both in vivo and in vitro. The efficacy of FTC, abrogated by M184V, was partially restored by A98S (IC90,FTC, 5169卤5931nM for A98S+M184V vs. 18477卤12478nM for M184V alone). 2016 Journal of global antimicrobial resistance Abstract HIV M184V 132 137 27532886 Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials. The resistance of DTG is mainly shown in 13 integrase mutations (including T97T/A, E138E/D, V151V/I, N155H, Q148, Y143C/H/R, T66A and E92Q). 2016 PloS one Abstract HIV E138D;E138E;E92Q;N155H;T66A;T97A;T97T;V151I;V151V;Y143C;Y143H;Y143R 83;83;134;101;125;75;75;92;92;114;114;114 90;90;138;106;129;81;81;99;99;123;123;123 IN 44 53 27532886 Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials. The ten major integrase mutations (including N155H, Y143C/R, Q148H/R, Y143Y/H, L74L/M, E92Q, E138E/A, Y143C, Q148Q and Y143S) can reduce the sensitivity of RAL and EVG. 2016 PloS one Abstract HIV E138A;E138E;E92Q;L74L;L74M;N155H;Q148H;Q148Q;Q148R;Y143C;Y143C;Y143H;Y143R;Y143S;Y143Y 93;93;87;79;79;45;61;109;61;102;52;70;52;119;70 100;100;91;85;85;50;68;114;68;107;59;77;59;124;77 IN 14 23 27539349 [Molecular epidemiology and transmission of HIV in Tianjin, 2015]. 5.3% of the NNRTI L100I HIV infectors transmitted the drug-resistant-mutation strain. 2016 Zhonghua liu xing bing xue za zhi Abstract HIV L100I 18 23 NNRTI 12 17 27541578 Design, Synthesis, and Evaluation of Thiophene[3,2-d]pyrimidine Derivatives as HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with Significantly Improved Drug Resistance Profiles. Compound 27 was the most potent; compared with ETV, its antiviral efficacy was 3-fold greater against WT, 5-7-fold greater against Y181C, Y188L, E138K, and F227L+V106A, and nearly equipotent against L100I and K103N, though somewhat weaker against K103N+Y181C. 2016 Journal of medicinal chemistry Abstract HIV E138K;F227L;K103N;K103N;L100I;V106A;Y181C;Y181C;Y188L 145;156;209;247;199;162;131;253;138 150;161;214;252;204;167;136;258;143 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5muM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs. 2016 Bioorganic & medicinal chemistry letters Abstract HIV A128T 227 232 IN 233 235 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. While resistance of one of the Envs to neutralization by autologous plasma antibodies with shorter V1 loop length was found to be correlated with a N332S mutation, resistance to neutralization of rest of the Envs was found to be associated with longer V1 loop length and acquisition of protective N-glycans. 2016 Retrovirology Abstract HIV N332S 148 153 Env;Env 31;208 35;212 27576689 Effects of Hinge-region Natural Polymorphisms on Human Immunodeficiency Virus-Type 1 Protease Structure, Dynamics, and Drug Pressure Evolution. E35D and R57K), x-ray structures reveal an altered network of interactions that replace the salt bridge thus stabilizing the structural integrity between the flap and hinge regions. 2016 The Journal of biological chemistry Abstract HIV R57K;E35D 9;0 13;4 27576689 Effects of Hinge-region Natural Polymorphisms on Human Immunodeficiency Virus-Type 1 Protease Structure, Dynamics, and Drug Pressure Evolution. Here, the impacts of the hinge-region natural polymorphism at residue 35, glutamate to aspartate (E35D), alone and in conjunction with residue 57, arginine to lysine (R57K), are characterized with the goal of understanding how altered salt bridge interactions between the hinge and flap regions are associated with changes in structure, motional dynamics, conformational sampling, kinetic parameters, and inhibitor affinity. 2016 The Journal of biological chemistry Abstract HIV E35D;R57K 98;167 102;171 27576689 Effects of Hinge-region Natural Polymorphisms on Human Immunodeficiency Virus-Type 1 Protease Structure, Dynamics, and Drug Pressure Evolution. The combined results reveal that the single E35D substitution leads to diminished salt bridge interactions between residues 35 and 57 and gives rise to the stabilization of open-like conformational states with overall increased backbone dynamics. 2016 The Journal of biological chemistry Abstract HIV E35D 44 48 27588613 Dolutegravir monotherapy as treatment de-escalation in HIV-infected adults with virological control: DoluMono cohort results. One patient chose to discontinue DTG monotherapy and another developed confirmed virological failure (HIV RNA 538 copies/ml) with new INSTI mutations (Q148H/G140S). 2017 Antiviral therapy Abstract HIV Q148H;G140S 151;157 156;162 INSTI 134 139 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. A mutation in a conserved residue (S40A) that does not reduce Gag interaction with Alix and therefore did not reduce budding efficiency was further investigated. 2016 Retrovirology Abstract HIV S40A 35 39 Gag 62 65 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Whether introduced into the HIV-1 NL4-3 strain genome or a model protease (PR) precursor, S40A reduced production of mature PR. 2016 Retrovirology Abstract HIV S40A 90 94 PR;PR;PR 65;75;124 73;77;126 27603287 In-depth analysis of HIV-1 drug resistance mutations in HIV-infected individuals failing first-line regimens in West and Central Africa. Five additional independently selected mutations (I94L, L109I, V111L, T139R and T165L) were statistically associated with treatment. 2016 AIDS (London, England) Abstract HIV I94L;L109I;T139R;T165L;V111L 50;56;70;80;63 54;61;75;85;68 27603287 In-depth analysis of HIV-1 drug resistance mutations in HIV-infected individuals failing first-line regimens in West and Central Africa. RESULTS: All RTI-DRM from the 2015 International Antiviral Society list, except F227C, and nine mutations from other expert lists were observed to confer extensive resistance and cross-resistance. 2016 AIDS (London, England) Abstract HIV F227C 80 85 RT 13 16 27603287 In-depth analysis of HIV-1 drug resistance mutations in HIV-infected individuals failing first-line regimens in West and Central Africa. The proportion of sequences with multiple mutations and the frequency of all thymidine analog mutations, M184V, certain NNRTIS, I94L and L109I showed substantial increase with time on ART. 2016 AIDS (London, England) Abstract HIV I94L;L109I;M184V 128;137;105 132;142;110 NNRTI 120 125 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Although HLA-B*81:01 was expressed by both grandmother and grand-daughter, autologous virus in each subject encoded an escape mutation L188F within the immunodominant HLA-B*81:01-restricted Gag-specific epitope TL9 (TPQDLNTML, Gag 180-188). 2016 Retrovirology Abstract HIV L188F 135 140 Gag;Gag 190;227 193;230 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. CONCLUSION: These findings suggest alternative sequences of events: the transmission of the uncompensated low fitness L188F to both children, potentially contributing to slow progression in both, consistent with previous studies indicating that disease progression in children can be influenced by the replicative capacity of the transmitted virus; or the transmission of fully compensated virus, and slow progression here principally the result of HLA-independent host-specific factors, yet to be defined. 2016 Retrovirology Abstract HIV L188F 118 123 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Since the transmitted virus can influence paediatric and adult HIV disease progression, we investigated the impact of the L188F mutant on replicative capacity. 2016 Retrovirology Abstract HIV L188F 122 127 HIV diseases 63 74 27624569 Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection. CONCLUSIONS: Although signature InSTI substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, polymorphisms and substitutions conferring low-level resistance to raltegravir and elvitegravir were frequently found in a baseline genotypic test. 2017 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 70;79;79;79;61;61 75;88;88;88;68;68 INSTI 32 37 27624569 Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. 2017 The Journal of antimicrobial chemotherapy Abstract HIV Q95K 64 68 27629070 Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184V 65 71 27630839 Identification of HIV Mutation as Diagnostic Biomarker through Next Generation Sequencing. The common mutations were identified at genome locations 1908 and 2104 as missense and silent mutations respectively, conferring S37N and S3S found on aspartic protease and reverse transcriptase subunits. 2016 Journal of clinical and diagnostic research Abstract HIV S37N 129 133 RT;PR 173;160 194;168 27630839 Identification of HIV Mutation as Diagnostic Biomarker through Next Generation Sequencing. This was especially the case for, missense mutation S37N which could cause an amino acid change in viral proteases thus reducing the binding affinity of some protease inhibitors. 2016 Journal of clinical and diagnostic research Abstract HIV S37N 52 56 PR;PR 105;158 114;166 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Criteria adopted for multi-NRTI resistance mutation were either presence of K65R or 3 or more thymidine analog mutations (TAMs) or presence of M184V along with 2 TAMs.Of the 844 study participants, virological suppression at 1 year was achieved in 87.7% of individuals. 2016 Medicine Abstract HIV K65R;M184V 76;143 80;148 NRTI 27 31 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. K65R mutation was significantly associated with tenofovir (TDF)-based failing regimen (P < 0.001).The study supports early linkage of HIV-infected individuals to the program for ART initiation, adherence improvement, and introduction of viral load monitoring. 2016 Medicine Abstract HIV K65R 0 4 HIV infections 134 146 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. With recent introduction of TDF-based regimen, the emergence of K65R needs to be monitored closely among HIV-1 subtype C-infected Indian population. 2016 Medicine Abstract HIV K65R 64 68 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. A recombinant virus with the BIC-selected M50I/R263K dual mutations in IN exhibited only 2.8-fold reduced susceptibility to BIC compared to wild-type virus. 2016 Antimicrobial agents and chemotherapy Abstract HIV M50I;R263K 42;47 46;52 IN 71 73 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. Vpr and Gag interaction is required to counteract TSG101 overexpression effect since Vpr A30F mutant which is unable to interact with Gag and incorporate into virions, reduced ability to prevent Gag accumulation and to rescue VLP production. 2016 PloS one Abstract HIV A30F 89 93 Vpr;Vpr;Gag;Gag;Gag 0;85;8;134;195 3;88;11;137;198 27654295 HIV-1 Escape from a Peptidic Anchor Inhibitor through Stabilization of the Envelope Glycoprotein Spike. Interestingly, a number of escape viruses acquired substitutions in the C1 domain of the gp120 subunit (A60E, E64K, and H66R) that rendered these viruses dependent on the inhibitor. 2016 Journal of virology Abstract HIV A60E;E64K;H66R 104;110;120 108;114;124 gp120 89 94 27659398 New insights into the interaction between pyrrolyl diketoacids and HIV-1 integrase active site and comparison with RNase H. Importantly, the tested DKAs demonstrated good effectiveness against HIV-1 Raltegravir resistant Y143A and N155H INs, thus showing an interaction pattern with relevant differences if compared with the first generation IN inhibitors. 2016 Antiviral research Abstract HIV N155H;Y143A 107;97 112;102 IN;IN 113;218 116;220 27659733 HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa. After M184V/I (82.7%), K65R was the most common NRTI mutation (45.8%). 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184I;M184V 23;6;6 27;13;13 NRTI 48 52 27659733 HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa. CONCLUSIONS: The introduction of tenofovir-based first-line regimens has dramatically increased the prevalence of K65R mutations in the HIV-1-infected South African population. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 114 118 HIV infections 136 150 27659733 HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa. K103N (48.9%) and V106M (34.9%) were the most common NNRTI mutations. 2017 The Journal of antimicrobial chemotherapy Abstract HIV V106M;K103N 18;0 23;5 NNRTI 53 58 27659733 HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa. The prevalence of K65R increased to 57.5% in patients failing a tenofovir regimen without prior stavudine exposure. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 18 22 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Here, we investigate the mechanism of the two most prevalent NNRTI-associated mutations with K103N or Y181C substitution. 2016 Viruses Abstract HIV K103N;Y181C 93;102 98;107 NNRTI 61 66 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Results showed that the virus and RT with K103N/Y188F substitutions displayed similar resistance levels to the virus and RT with K103N substitution versus NNRTIs. 2016 Viruses Abstract HIV K103N;K103N;Y188F 42;129;48 47;134;53 NNRTI;RT;RT 155;34;121 161;36;123 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. These results suggest that the hydrogen bond between N103 and Y188 may not play an important role in the resistance of the K103N variant to NNRTIs. 2016 Viruses Abstract HIV K103N 123 128 NNRTI 140 146 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Virus and reverse transcriptase (RT) with K103N/Y188F, K103A, or K103E substitutions and with Y181F, Y188F, or Y181F/Y188F substitutions were employed to study the resistance mechanism of the K103N and Y181C mutants, respectively. 2016 Viruses Abstract HIV K103A;K103E;K103N;K103N;Y181C;Y181F;Y181F;Y188F;Y188F;Y188F 55;65;42;192;202;94;111;48;117;101 60;70;47;197;207;99;116;53;122;106 RT;RT 10;33 31;35 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Virus and RT containing Y181F, Y188F, or Y181F/Y188F substitution exhibited either enhanced or similar susceptibility to NNRTIs compared with the wild type (WT) virus. 2016 Viruses Abstract HIV Y181F;Y181F;Y188F;Y188F 24;41;31;47 29;46;36;52 NNRTI;RT 121;10 127;12 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. An analysis of C34-resistant mutations revealed that the I37K mutation in gp41 HR1 is a key mutation for C34 resistance, low infectivity, neutralization sensitivity, epitope exposure, and slow fusion kinetics. 2016 Retrovirology Abstract HIV I37K 57 61 gp41 74 78 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. In the absence of L204I, the effect of N126K was antagonistic to that of I37K. 2016 Retrovirology Abstract HIV I37K;L204I;N126K 73;18;39 77;23;44 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Our observations indicate that the "conformational unmasking" of envelope glycoprotein by an I37K mutation is one of the mechanisms of neutralization sensitivity enhancement. 2016 Retrovirology Abstract HIV I37K 93 97 Env 65 73 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The N126K mutation in the gp41 HR2 domain contributed to C34 resistance and neutralization sensitivity to anti-CD4 binding site antibodies. 2016 Retrovirology Abstract HIV N126K 4 9 gp41 26 30 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The results of a molecular dynamic simulation of the envelope trimer confirmation suggest that an I37K mutation induces the augmentation of structural fluctuations prominently in the interface between gp41 and gp120. 2016 Retrovirology Abstract HIV I37K 98 102 Env;gp120;gp41 53;210;201 61;215;205 27677159 Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. CONCLUSION: The appearance of K65K/K66K in drug-treated individuals was largely independent of TAMs, suggesting alternative factors are likely associated with their emergence. 2016 AIDS (London, England) Abstract HIV K65K;K66K 30;35 34;39 27677159 Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. Here, we investigated the temporal appearance of K65K/K66K relative to TAMs in a HIV-1 cohort, their prevalence over time, and their impact on viral fitness in the context of patient-derived reverse transcriptase sequences. 2016 AIDS (London, England) Abstract HIV K65K;K66K 49;54 53;58 RT 191 212 27677159 Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. OBJECTIVE: Synonymous substitutions K65K/K66K in HIV-1 reverse transcriptase alleviate fitness and fidelity defects in HIV-1 molecular clones harboring thymidine analogue mutations (TAMs); however, their potential for transmission and persistence is unknown. 2016 AIDS (London, England) Abstract HIV K65K;K66K 36;41 40;45 RT 55 76 27677159 Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. RESULTS: The prevalence of K65K/K66K in drug-naive individuals tripled from 11% in 1997 to 37% in 2014 (P < 0.0001, n = 5221), with K66K mainly accounting for the increase. 2016 AIDS (London, England) Abstract HIV K65K;K66K;K66K 27;32;132 31;36;136 27677159 Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. The increasing K65K/K66K prevalence to over a third of treatment-naive individuals in the mostly subtype B DTP cohort and their ability to confer a fitness advantage to multidrug-resistant virus might explain the transmission and persistence of virus harbouring K65K/K66K in untreated individuals, and highlights their role in adaptive HIV-1 evolution. 2016 AIDS (London, England) Abstract HIV K65K;K65K;K66K;K66K 15;262;267;20 19;266;271;24 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. More importantly, we show that at least two of the three clinically relevant drug resistant integrase mutants we tested, N155H and G140S/Q148H, which reduce the enzymatic activity of integrase, can cause the same sorts of aberrant integrations, even in the absence of drugs. 2016 Retrovirology Abstract HIV G140S;N155H;Q148H 131;121;137 136;126;142 IN;IN 92;183 101;192 27697032 Prevalence of HIV-1 Subtypes and Antiretroviral Drug Resistance Mutations in Nepal. DRMs to NVP, K103N and V179D, and to NRTIs were observed at 11.1% (2/18) and 5% (1/20), respectively. 2016 Current HIV research Abstract HIV K103N;V179D 13;23 18;28 NRTI 37 42 27697032 Prevalence of HIV-1 Subtypes and Antiretroviral Drug Resistance Mutations in Nepal. The minor protease inhibitors (PI) associated mutations (A71T/V and T74S) were observed in 5/35 (14.3%) subjects. 2016 Current HIV research Abstract HIV A71T;A71V;T74S 57;57;68 64;64;72 PR;PI 10;31 18;33 27697032 Prevalence of HIV-1 Subtypes and Antiretroviral Drug Resistance Mutations in Nepal. The prevalence of DRMs to rilpivirine for E138A/G was 5.7%. 2016 Current HIV research Abstract HIV E138A;E138G 42;42 49;49 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. Besides, a significant transmission of viruses with drug resistant mutations at V179D/E were found in the networks. 2016 Scientific reports Abstract HIV V179D;V179E 80;80 87;87 27704215 Natural occurrence of NS5B inhibitor resistance-associated variants in Brazilian patients infected with HCV or HCV and HIV. RAVs detected in HCV-1a sequences were V321A (1.6 %), M414V (1.3 %), A421V (21.4-23.7 %), A421G (1.3 %) and Y448H (1.3 %); and in HCV-1b sequences were L159F (16.1 %), C316N (7.1-16.3 %) and A421V (3.2-6.3 %). 2017 Archives of virology Abstract HIV A421G;A421V;A421V;C316N;L159F;M414V;V321A;Y448H 90;69;191;168;152;54;39;108 95;74;196;173;157;59;44;113 27704821 Discovery and Development of the Anti-Human Immunodeficiency Virus Drug, Emtricitabine (Emtriva, FTC). For example, passage studies indicated that the compound rapidly selected for a single resistant mutant, M184V, and that this strain was 500-1000-fold less sensitive to FTC than was wild-type virus. 2016 Accounts of chemical research Abstract HIV M184V 105 110 27722739 Molecular insight on the binding of NNRTI to K103N mutated HIV-1 RT: molecular dynamics simulations and dynamic pharmacophore analysis. In this study, a cumulative 240 ns of molecular dynamic (MD) simulations of WT HIV-1 RT and its corresponding K103N mutated form, complexed with rilpivirine, were performed in solution. 2016 Molecular bioSystems Abstract HIV K103N 110 115 RT 85 87 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Through a series of investigations on the evolution, mutational profile, and phenotype of the virus and the resultant humoral immune response in infected rhesus macaques, we found that the E32K mutation in the Env C1 domain was associated with macaque pathogenesis, and that the electrostatic interactions in Env may favor E32K at the gp120 N terminus and "lock" the binding to heptad repeat 1 of gp41 in the trimer and produce a SHIVenv with increased fitness and pathogenesis during macaque infections. 2016 Virology Abstract HIV E32K;E32K 189;323 193;327 gp120;gp41;Env;Env 335;397;210;309 340;401;213;312 27725181 Membrane Interactions of the Mason-Pfizer Monkey Virus Matrix Protein and Its Budding Deficient Mutants. To address this issue, we compared the structures and membrane affinity of the Mason-Pfizer monkey virus (M-PMV) wild-type MA with its two budding deficient double mutants, that is, T41I/T78I and Y28F/Y67F. 2016 Journal of molecular biology Abstract HIV T41I;T78I;Y28F;Y67F 182;187;196;201 186;191;200;205 Matrix 123 125 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. K103N and M41L were the most frequent SDRMs and were present mostly in proportions >20% in each individual. 2016 PloS one Abstract HIV M41L;K103N 10;0 14;5 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. Moreover, the reverse transcription of HIV-1 mutant bearing capsid G89V showed insensitivity to restriction by TRIM11, indicating that the viral determinant of restriction by TRIM11 might reside on capsid. 2016 Retrovirology Abstract HIV G89V 67 71 RT;Capsid;Capsid 14;60;198 35;66;204 27737783 Development of a phenotypic susceptibility assay for HIV-1 integrase inhibitors. Solely a Q148H+G140S variant presented reduced susceptibility to dolutegravir. 2016 Journal of virological methods Abstract HIV G140S;Q148H 15;9 20;14 27737783 Development of a phenotypic susceptibility assay for HIV-1 integrase inhibitors. While raltegravir resistance profiles presented a high cross-resistance to elvitegravir, dolutegravir maintained in-vitro activity in spite of the Y143R and N155H mutations, confirming the strong activity of dolutegravir against raltegravir-resistant viruses. 2016 Journal of virological methods Abstract HIV N155H;Y143R 157;147 162;152 27742812 Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK. The most common mutations detected at >20% and 2%-20% mutation frequency differed for each drug class, these respectively being: L90M (n = 7) and M46IL (n = 10) for PIs; T215rev (n = 9) and D67GN (n = 4) for NRTIs; and K103N (n = 5) and G190E (n = 2) for NNRTIs. 2017 The Journal of antimicrobial chemotherapy Abstract HIV D67G;D67N;G190E;K103N;L90M;M46I;M46L 190;190;237;219;129;146;146 195;195;242;224;133;151;151 NNRTI;NRTI;PI 255;208;165 261;213;168 27750023 Surveillance of Transmitted Drug Resistance in HIV-1-Infected Youths Aged 16 to 25 Years, a Decade After Scale-up of Antiretroviral Therapy in Hebei, China. All TDR mutations (M46L/I, Y181C, K101E, and G190E) were found only in youths infected with HIV-1 through sexual activity. 2017 AIDS research and human retroviruses Abstract HIV G190E;K101E;M46I;M46L;Y181C 45;34;19;19;27 50;39;25;25;32 27750023 Surveillance of Transmitted Drug Resistance in HIV-1-Infected Youths Aged 16 to 25 Years, a Decade After Scale-up of Antiretroviral Therapy in Hebei, China. TDR mutations resided in CRF01_AE (M46I/L and G190E) and subtype B (Y181C and K101E). 2017 AIDS research and human retroviruses Abstract HIV G190E;K101E;M46I;M46L;Y181C 46;78;35;35;68 51;83;42;42;74 27750153 Discovery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment rearrangement. Especially, 8 displayed outstanding potency against L100I (EC50 = 17 nM with a 2.8-fold resistance ratio) and 18 was relatively more potent to E138K mutant (EC50 = 43 nM with a 4.7-fold resistance ratio). 2017 European journal of medicinal chemistry Abstract HIV E138K;L100I 143;52 148;57 27750153 Discovery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment rearrangement. Furthermore, most compounds maintained high activity agaist various single HIV-1 mutants (L100I, K103N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC50 values in low-micromolar to double-digit nanomolar concentration ranges. 2017 European journal of medicinal chemistry Abstract HIV F227L;E138K;K103N;L100I;V106A;Y181C 148;104;97;90;154;111 153;109;102;95;159;116 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Subtilisin treatment of infected cells demonstrated that the N659D mutant was more tethered at the cell surface. 2016 Viruses Abstract HIV N659D 61 66 27758855 Core Binding Factor beta Protects HIV, Type 1 Accessory Protein Viral Infectivity Factor from MDM2-mediated Degradation. Cycloheximide chase analyses revealed that Vif E88A/W89A, which does not interact with CBFbeta, degraded faster than wild-type Vif in MDM2-proficient cells but not in MDM2-null cells, suggesting that Vif stabilization by CBFbeta is mainly caused by impairing MDM2-mediated degradation. 2016 The Journal of biological chemistry Abstract HIV E88A;W89A 47;52 51;56 Vif;Vif;Vif 43;127;200 46;130;203 27758855 Core Binding Factor beta Protects HIV, Type 1 Accessory Protein Viral Infectivity Factor from MDM2-mediated Degradation. We identified Vif R93E as a Vif variant that does not bind to MDM2, and the virus with this substitution mutation was more resistant to APOBEC3G than the parental virus. 2016 The Journal of biological chemistry Abstract HIV R93E 18 22 Vif;Vif 14;28 17;31 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Of 30 sequences (47.6%) with INSTI-resistant mutations from raltegravir-experienced patients, 17 harboured Q148H/K/R, 8 N155H, and 6 Y143C/R. 2016 Scientific reports Abstract HIV Y143C;Q148H;Q148K;Q148R 133;107;107;107 140;116;116;116 INSTI 29 34 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Of these 12 sequences, 11 harboured Q148H/K/R, one Y143R, and none N155H. 2016 Scientific reports Abstract HIV N155H;Q148H;Q148K;Q148R;Y143R 67;36;36;36;51 72;45;45;45;56 27789684 Pretreatment HIV-1 drug resistance in Argentina: results from a surveillance study performed according to WHO-proposed new methodology in 2014-15. The most common mutation was K103N. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K103N 29 34 27790293 Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans. METHOD: Demographic data were collected from 103 consenting patients; lipoprotein levels were determined and blood samples were successfully genotyped for both apolipoprotein B 2488C>T Xba1 and apolipoprotein B 4154G>A p.Gln4154Lys EcoR1 polymorphisms by real time polymerase chain reaction. 2016 The open AIDS journal Abstract HIV C2488T;G4154A;Q4154K 177;211;211 184;231;231 Pol 265 275 27795333 Rapid Detection of Common HIV-1 Drug Resistance Mutations by Use of High-Resolution Melting Analysis and Unlabeled Probes. The analytical sensitivities of the HRMA assays were 5% of mixed species for K103N and Y181C and 20% for M184V. 2017 Journal of clinical microbiology Abstract HIV K103N;M184V;Y181C 77;105;87 82;110;92 27795333 Rapid Detection of Common HIV-1 Drug Resistance Mutations by Use of High-Resolution Melting Analysis and Unlabeled Probes. When applied to 153 HIV-1 patient specimens previously genotyped by Sanger population sequencing, HRMA correctly assigned drug sensitivity or resistance profiles to 80% of the samples at codon 103 (K103K/N) (Cohen's kappa coefficient [kappa] > 0.6; P < 0.05), 90% at 181 (Y181Y/C) (kappa > 0.74, P < 0.05), and 80% at 184 (M184M/V) (kappa > 0.62; P < 0.05). 2017 Journal of clinical microbiology Abstract HIV K103K;K103N;M184M;M184V;Y181C;Y181Y 198;198;323;323;272;272 205;205;330;330;279;279 27795445 Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the IN Precursor Form with Reverse Transcriptase. Notably, replacement of Tyr15 with phenylalanine was tolerated for all IN functions, demonstrating that a benzene ring of the aromatic side chain is a key moiety for IN assembly and functions. 2017 Journal of virology Abstract HIV Y15F 24 48 IN;IN 71;166 73;168 27798967 Low Rates of Transmitted Drug Resistance Among Newly Identified HIV-1 Seroconverters in Rural Rakai, Uganda. Two individuals had a single non-nucleoside reverse transcriptase inhibitor mutation each, K101E and K103N, and one had a single protease inhibitor mutation, M46I. 2017 AIDS research and human retroviruses Abstract HIV K101E;K103N;M46I 91;101;158 96;106;162 NNRTI;PR 29;129 65;137 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. The primary mutations observed in the study were against nucleoside reverse transcriptase inhibitors (NRTIs) which were M184V (79.45%) and K103N (33.70%) in nonnucleoside reverse transcriptase inhibitors (NNRTIs). 2016 BioMed research international Abstract HIV K103N;M184V 139;120 144;125 NNRTI;NRTI;NNRTI;NRTI 157;57;205;102 192;89;211;107 27834135 Synthesis and biological evaluation of benzophenone derivatives as potential HIV-1 inhibitors. GW678248, is one of the most potent benzophenone derivatives, exhibiting high potency against a panel of HIV-1 virus (wild-type, K103N mutant, Y181C, etc.) at 1 nM/L concentrations. 2016 Medicinal chemistry (Shariqah (United Arab Emirates)) Abstract HIV K103N;Y181C 129;143 134;148 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. An alanine-to-valine substitution at position 84, located in alpha helix 2 of Nef, was sufficient to alter the rate of turnover of an otherwise highly expressed Nef protein. 2016 mSphere Abstract HIV A84V 3 48 Nef;Nef 78;161 81;164 27842871 Trends in drug resistance-associated mutations in a real-life cohort of Italian patients infected with HIV-1. Interestingly, analysis of the integrase gene disclosed an increased resistance to integrase inhibitors, mainly regarding N155H, detected in 32.6% of raltegravir-treated patients in 2012-2014. 2015 Journal of global antimicrobial resistance Abstract HIV N155H 122 127 IN;IN 31;83 40;92 27858889 Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). 2016 Medicine Abstract HIV K103N;Y181C 22;32 27;37 NNRTI;NNRTI 62;111 98;117 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. In comparison to JRFL (E168K), JRCSF Env binds more efficiently to PG9/PGT145 class of V1/V2-directed conformational antibodies. 2016 Retrovirology Abstract HIV E168K 23 28 Env 37 40 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Membrane bound form of modified JRCSF Env containing the N197D mutation binds to CD4-bs-directed neutralizing antibodies better than JRFL, without debilitating its ability to bind quaternary epitope-directed neutralizing antibodies or exposing the CD4i antibody epitopes. 2016 Retrovirology Abstract HIV N197D 57 62 Env 38 41 27875973 Structural Modifications of Diarylpyrimidine-quinolone Hybrids as Potent HIV-1 NNRTIs with an Improved Drug Resistance Profile. A few of these hybrids displayed moderate inhibitory activity against wt HIV-1 replication at submicromolar level, however, all of them lacked inhibitory activity against the double mutant virus (K103N/Y181C), which is the most prevalent NNRTI resistant-associated double mutant observed in the clinic. 2016 Current pharmaceutical design Abstract HIV K103N;Y181C 196;202 201;207 NNRTI 238 243 27875973 Structural Modifications of Diarylpyrimidine-quinolone Hybrids as Potent HIV-1 NNRTIs with an Improved Drug Resistance Profile. The most promising hybrid 5c displayed a significant EC50 value of 0.0096 muM against HIV-1 IIIB and of 0.98 muM against K103N/Y181C. 2016 Current pharmaceutical design Abstract HIV K103N;Y181C 121;127 126;132 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. Additionally, we have identified an HIV-1 capsid mutant, N74D, that is able to escape the restriction in the marmoset B-LCLs. 2016 Scientific reports Abstract HIV N74D 57 61 Capsid 42 48 27895013 Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa. Mutations L100I and K103N were significantly more frequent in samples with >500-fold resistance to DPV compared to samples with a <=500-fold resistance. 2017 Antimicrobial agents and chemotherapy Abstract HIV K103N;L100I 20;10 25;15 27897226 Viral and Host Characteristics of Recent and Established HIV-1 Infections in Kisumu based on a Multiassay Approach. Overall, HIV-1 subtype A (63%), D (15%), C (3%), G (1%) and recombinants (18%), two monophyletic dyads and intrinsic viral mutations (V81I, V81I/V, V108I/V and K101Q) were observed. 2016 Scientific reports Abstract HIV K101Q;V108I;V108V;V81I;V81I;V81V 160;148;148;134;140;140 165;155;155;138;146;146 27900665 Use of Capillary Electrophoresis to Study the Binding Interaction of Aptamers with Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT : Studying the Binding Interaction of Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT with Aptamers by Performing the Capillary Electrophoresis. In addition, RT1t49 could bind specifically with the wild-type, K103N, and double mutants in Escherichia coli lysate. 2017 Applied biochemistry and biotechnology Abstract HIV K103N 64 69 27900665 Use of Capillary Electrophoresis to Study the Binding Interaction of Aptamers with Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT : Studying the Binding Interaction of Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT with Aptamers by Performing the Capillary Electrophoresis. Therefore, we utilized non-equilibrium capillary electrophoresis of equilibrium mixture (NECEEM) to study the interaction of three HIV-1 RTs (wild type, K103N, and double mutant (K103N/Y181C)) with RT1t49 and RT12 aptamers. 2017 Applied biochemistry and biotechnology Abstract HIV K103N;K103N;Y181C 179;153;185 184;158;190 RT;RT 137;209 140;211 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Because the E12A mutant lacks the activities for trimer formation on the basis of the analytical ultra-centrifuge studies on the sedimentation distribution of p17 (Fledderman et al. 2016 PloS one Abstract HIV E12A 12 16 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Furthermore, the analyses of the order parameter revealed that less flexible structures existed at each loop region in E12A. 2016 PloS one Abstract HIV E12A 119 123 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In contrast, the average values of the kinetic rate constants for amide proton exchange for residues located in all loop regions were slightly lower in E12A than in wild type. 2016 PloS one Abstract HIV E12A 152 156 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Interestingly, the structures of the regions including the alpha1-2 loop and helix 5 of E12A exhibited more significant conformational exchanges with the NMR time-scale than those of wild type. 2016 PloS one Abstract HIV E12A 88 92 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The chemical shift perturbation from the comparison between wild type and E12A suggested the existence of an electrostatic interaction in wild type between E12 and H89 (located in helix 4). 2016 PloS one Abstract HIV E12A 74 78 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The dynamic structure of E12A was examined under physiological conditions by both amide proton exchange and relaxation studies. 2016 PloS one Abstract HIV E12A 25 29 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. To test the existence of the salt bridge and stability of the HIV-1 p17 matrix protein, an E12A (mutated at helix 1) was established to abolish possible electrostatic interactions. 2016 PloS one Abstract HIV E12A 91 95 Matrix 72 78 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Under lower pH conditions, for further destabilization, the helix 1 and alpha2-3 loop in E12A became more fluctuating than at physiological pH. 2016 PloS one Abstract HIV E12A 89 93 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Unexpectedly, the studies using urea denaturation indicated that the E12A substitution slightly stabilized the protein. 2016 PloS one Abstract HIV E12A 69 73 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. 2017 Journal of neurovirology Abstract HIV C31C;C31S 102;93 106;97 Tat 89 92 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status. 2017 Journal of neurovirology Abstract HIV C31S 102 106 Tat 98 101 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. 2017 Journal of neurovirology Abstract HIV C31S 4 8 Tat 0 3 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). 2017 Journal of neurovirology Abstract HIV C31C;C31S 115;44 119;48 Tat;Tat 40;97 43;100 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. 2017 Journal of neurovirology Abstract HIV C31S 126 130 Tat 113 116 27917773 Mutations of mtDNA polymerase-gamma and hyperlactataemia in the HIV-infected Zulu population of South Africa. Genomic DNA from 113 samples was used for subsequent allelic discrimination polymerase chain reaction screening for the R964C and E1143G single-nucleotide polymorphisms of POLG1. 2016 South African medical journal Abstract HIV E1143G;R964C 130;120 136;125 Pol;Pol 76;172 86;175 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. The proposed methods are applied to the ACTG 244 clinical trial of HIV infected patients being treated with Zidovudine to examine the effects of antiretroviral treatment switching before and after HIV develops the T215Y/F drug resistance mutation. 2017 Biometrics Abstract HIV T215F;T215Y 214;214 221;221 HIV infections 67 79 27928014 Histidine 375 Modulates CD4 Binding in HIV-1 CRF01_AE Envelope Glycoproteins. We observed that reversion of amino acid 375 to a serine (H375S) resulted in a loss of functionality of both CRF01_AE Envs as measured by a dramatic loss in infectivity and ability to mediate cell-to-cell fusion. 2017 Journal of virology Abstract HIV H375S 58 63 Env 118 122 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). 2016 The American journal of tropical medicine and hygiene Abstract HIV A403C;G145A 314;304 319;310 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. A high incidence of CXCR4-tropic HIV-1 variants and a higher rate of secondary mutations influencing the virus fitness (K20R, L10V, and I) are observed among the virus specimens isolated from newly infected individuals. 2016 BioMed research international Abstract HIV K20R;L10V 120;126 124;130 27959842 [HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area]. The resistance mutations detected in naives were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. 2016 Medicina Abstract HIV K103N 120 125 NRTI 69 101 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. An additional K20R mutation anchors an altered conformation of the hinge loop. 2016 PloS one Abstract HIV K20R 14 18 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Comparable binding affinity of 8000-fold weaker than PR is seen for drug resistant mutant PR20, which bears 3 mutations associated with major resistance to darunavir (I47V, I54L and I84V). 2016 PloS one Abstract HIV I47V;I54L;I84V 167;173;182 171;177;186 PR;PR 53;90 55;92 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Despite its 17 mutations, PRS17 has only one mutation (V82S) in the inhibitor/substrate binding cavity, yet exhibits high resistance to all clinical inhibitors. 2016 PloS one Abstract HIV V82S 55 59 PR 26 28 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Distal mutations A71V, L90M and I93L propagate alterations to the catalytic site of PRS17. 2016 PloS one Abstract HIV A71V;I93L;L90M 17;32;23 21;36;27 PR 84 86 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Flap mutations M46L and G48V in PRS17/DRV complex alter the Phe53 conformation by steric hindrance between the side chains. 2016 PloS one Abstract HIV G48V;M46L 24;15 28;19 PR 32 34 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PRS17, the hinge loop cluster of mutations, E35D, M36I and S37D, contributes to the altered flap dynamics by a mechanism similar to that of PR20. 2016 PloS one Abstract HIV E35D;M36I;S37D 47;53;62 51;57;66 PR;PR 3;143 5;145 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Inhibitor-free PRS17 shows an open flap conformation with a curled tip correlating with G48V flap mutation. 2016 PloS one Abstract HIV G48V 88 92 PR 15 17 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with darunavir resistance, but has 10,000-fold weaker binding affinity relative to the wild type PR. 2016 PloS one Abstract HIV I47V;I50V;I54L;I54M;I84V;L76V 39;45;51;51;67;58 43;49;56;56;71;62 PR;PR 0;181 2;183 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Unlike the L10F mutation in PR20, L10I in PRS17 does not break the inter-subunit ion pair or diminish the dimer stability, consistent with a very low dimer dissociation constant comparable to that of wild type PR. 2016 PloS one Abstract HIV L10F;L10I 11;34 15;38 PR;PR;PR 28;42;210 30;44;212 27993614 Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes. Mutations associated with integrase resistance were observed in seven of the 106 (7%) clinical samples [one sample: Q148K; E138K; G140A; two samples: T97A and four samples: L74I]. 2017 Journal of virological methods Abstract HIV E138K;G140A;L74I;Q148K;T97A 123;130;173;116;150 128;135;177;121;154 IN 26 35 27993614 Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes. Of the four samples with L74I, 3 were subtype G. 2017 Journal of virological methods Abstract HIV L74I 25 29 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. Interestingly, K26R mutation in Vif abolishes degradation of A3G by the proteasome but has no effect at the translational level, indicating these two pathways are independent. 2016 Scientific reports Abstract HIV K26R 15 19 Vif 32 35 27999055 Unravelling the dynamics of selection of multiresistant variants to integrase inhibitors in an HIV-1-infected child using ultra-deep sequencing. At the last timepoint under raltegravir (week 17), Y143R emerged, leading to different resistance mutation patterns: single mutants N155H (47%) and Y143R (24%) and double mutants E92Q + N155H (13%), Y143R + N155H (2%) and E92Q + Y143R (2%). 2017 The Journal of antimicrobial chemotherapy Abstract HIV E92Q;E92Q;N155H;N155H;N155H;Y143R;Y143R;Y143R;Y143R 179;222;132;186;207;51;148;199;229 183;226;137;191;212;56;153;204;234 27999055 Unravelling the dynamics of selection of multiresistant variants to integrase inhibitors in an HIV-1-infected child using ultra-deep sequencing. The double mutant E92Q + N155H, conferring resistance to the entire integrase inhibitor class, including dolutegravir, emerged at week 8 (16%) and became rapidly dominant (57% by week 13). 2017 The Journal of antimicrobial chemotherapy Abstract HIV E92Q;N155H 18;25 22;30 IN 68 77 27999055 Unravelling the dynamics of selection of multiresistant variants to integrase inhibitors in an HIV-1-infected child using ultra-deep sequencing. The major DRM N155H conferring resistance to raltegravir and elvitegravir was detected in 4% of the sequences by week 4 using UDS, whereas it was not detected by Sanger sequencing. 2017 The Journal of antimicrobial chemotherapy Abstract HIV N155H 14 19 27999055 Unravelling the dynamics of selection of multiresistant variants to integrase inhibitors in an HIV-1-infected child using ultra-deep sequencing. The polymorphic substitution M50I was preferentially selected on resistant variants, especially on E92Q + N155H variants. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E92Q;M50I;N155H 99;29;106 103;33;111 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. A relatively nonpolymorphic accessory mutation A98G-12.0% was also common. 2016 BMC research notes Abstract HIV A98G 47 51 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. Also common were the accessory PI mutations L10I-27%, L10V-12.0% and L10F-5.0% that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations. 2016 BMC research notes Abstract HIV L10F;L10I;L10V 69;44;54 73;48;58 PI;PI;PI 31;98;166 33;100;168 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. Seven of the 36 patients on second line ART had major Protease Inhibitor (PI) associated DRMS including; V82A-7.0%, I54V, M46I and L33I (all 5.0%). 2016 BMC research notes Abstract HIV I54V;L33I;M46I;V82A 116;131;122;105 120;135;126;109 PR;PI 54;74 62;76 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The commonest clinically significant major resistance mutations associated with the highest levels of reduced susceptibility or virological response to the relevant Nucleoside Reverse Transcriptase Inhibitor (NRTI) were; the Non-thymidine analogue mutations (Non-TAMS) M184V-20.7% and K65R-8.0%; and the TAMs M41L and K70R (both 8.0%). 2016 BMC research notes Abstract HIV K65R;K70R;M184V;M41L 285;318;267;309 289;322;274;313 NRTI;NRTI 165;209 197;213 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The major Non-NRTI (NNRTI) mutations were K103N-19.0%, G190A-7.0% and Y181C-6.0%. 2016 BMC research notes Abstract HIV G190A;K103N;Y181C 55;42;70 60;47;75 NNRTI;NNRTI 10;20 18;25 28017554 Trends and predictors of HIV-1 acquired drug resistance in Minas Gerais, Brazil: 2002-2012. Resistance to NNRTI increased from 74.4% to 81.6%, mainly because of K103N mutation. 2017 The Brazilian journal of infectious diseases Abstract HIV K103N 69 74 NNRTI 14 19 28017912 Differences in the integrase and reverse transcriptase transmitted resistance patterns in Northern Poland. Clusters of nucleoside reverse transcriptase mutations in subtype D and integrase E157Q variants in subtype B were observed. 2017 Infection, genetics and evolution Abstract HIV E157Q 82 87 NRTI;IN 12;72 44;81 28017912 Differences in the integrase and reverse transcriptase transmitted resistance patterns in Northern Poland. Polymorphisms associated with resistance against integrase inhibitor, mostly E157Q, were found in 21.5% sequences and associated with female (31.91% vs. 2017 Infection, genetics and evolution Abstract HIV E157Q 77 82 IN 49 58 28034359 HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Cross-sectional Design. Among ART-naive patients, 6.7% harbored K103N, 28.6% had IN accessory-mutations (L74I, E157Q) and 26.7% carried CXCR4-tropic viruses. 2016 Current HIV research Abstract HIV E157Q;K103N;L74I 87;40;81 92;45;85 IN 57 59 28034359 HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Cross-sectional Design. At first-line failure, 79.2% harbored DRMs to nucleoside and non-nucleoside RT inhibitors, 33.3% had IN accessory-mutations (L68I, L74I, T97A, E157Q), and 47.4% carried CXCR4-tropic viruses. 2016 Current HIV research Abstract HIV E157Q;L68I;L74I;T97A 143;125;131;137 148;129;135;141 IN;RT 101;76 103;78 28034359 HIV-1 Drug Susceptibility to Potential Second- and Third-Line Antiretroviral Regimens among Cameroonian Patients: Evidence from a Cross-sectional Design. At second-line failure, 91.3% harbored multi-DRMs to PR-RT inhibitors (with 52.2% and 4.3% DRMs to second-generation NNRTIs and darunavir/r, respectively), 27.3% had IN accessory-mutations (L74I, T97A, E157EQ), and 37.5% carried CXCR4-tropic viruses. 2016 Current HIV research Abstract HIV E157E;E157Q;L74I;T97A 202;202;190;196 208;208;194;200 NNRTI;IN;PR;RT 117;166;53;56 123;168;55;58 28076335 Infrequent development of drug resistance in HIV-1-infected treatment-naive subjects after 96 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate. Primary resistance development to ARVs of the regimen occurred in 10 of 24 subjects in the E/C/F/TAF arm, and 8 of 24 subjects in the E/C/F/TDF arm (E/C/F/TAF: M184V/I, n=9; integrase strand-transfer inhibitor resistance-associated mutations [INSTI-RAMs], n=8; K65R/N, n=2; E/C/F/TDF: M184V/I, n=6; INSTI-RAMs, n=5; K65R/N, n=3). 2017 Antiviral therapy Abstract HIV K65N;K65N;K65R;K65R;M184I;M184I;M184V;M184V 261;316;261;316;160;285;160;285 267;322;267;322;167;292;167;292 IN;INSTI;INSTI 174;243;299 183;248;304 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. Genotypic resistance testing was available for 16/22 (72.7%) patients, of which 15 (93.8%) had at least one major mutation, most commonly M184V (81.2%) and K103NS (68.8%). 2017 AIDS research and therapy Abstract HIV K103N;K103S;M184V 156;156;138 162;162;143 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Both ligands inhibited HIV fusion on signaling-deficient CCR5 mutations (Tyr244Ala and Trp248Ala). 2016 Pharmacology research & perspectives Abstract HIV W248A;Y244A 87;73 96;83 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Finally, the efficacy switch mutation (Leu203Phe) - converting small-molecule antagonists/inverse agonists to full agonists biased toward G-protein activation - uncovered that also small-molecule agonists can function as direct HIV-1 cell entry inhibitors. 2016 Pharmacology research & perspectives Abstract HIV L203F 39 48 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Moreover, the steric hindrance CCR5 mutation (Gly286Phe) impaired fusion, presumably by a direct hindrance of gp120 interaction. 2016 Pharmacology research & perspectives Abstract HIV G286F 46 55 gp120 110 115 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. On CCR5 WT, Maraviroc and Aplaviroc inhibited fusion with high potencies (EC 50 values of 91 and 501 nM, respectively), whereas removal of key residues for both antagonists (Glu283Ala) or Maraviroc alone (Tyr251Ala) prevented fusion inhibition, establishing this assay as suitable for screening of HIV entry inhibitors. 2016 Pharmacology research & perspectives Abstract HIV E283A;Y251A 174;205 183;214 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Among them, 7 polymorphisms (L74I, K103N, V106A, Y181C, G190A, T215I and P225H) were known to be drug resistance mutations, 7 polymorphisms (E6D, E35D, S37N, I93L, E169D, T200V and T200E were considered to be potential drug resistance mutations, and 6 polymorphisms (T39A, K43E, S68N, Q197K, T200V and E224D) were newly found to have an association with drug resistance mutations, which formed a complex network of relationships. 2017 PloS one Abstract HIV E169D;E224D;E35D;E6D;G190A;I93L;K103N;K43E;L74I;P225H;Q197K;S37N;S68N;T200E;T200V;T200V;T215I;T39A;V106A;Y181C 164;302;146;141;56;158;35;273;29;73;285;152;279;181;171;292;63;267;42;49 169;307;150;144;61;162;40;277;33;78;290;156;283;186;176;297;68;271;47;54 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Result showed that 20 polymorphisms (E6D, Q18H, E35D, S37N, T39A, K43E, S68N, L74I, I93L, K103N, V106A, E169D, Y181C, G190A, Q197K, T200V, T200E, T215I, E224D and P225H) were strongly associated with AIDS related deaths. 2017 PloS one Abstract HIV E169D;E224D;E35D;E6D;G190A;I93L;K103N;K43E;L74I;P225H;Q18H;Q197K;S37N;S68N;T200E;T200V;T215I;T39A;V106A;Y181C 104;153;48;37;118;84;90;66;78;163;42;125;54;72;139;132;146;60;97;111 109;158;52;40;123;88;95;70;82;168;46;130;58;76;144;137;151;64;102;116 AIDS 200 204 28100618 Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. Conversely, the replacement of His 375 by a serine residue (H375S) within HIV-1 CRF01_AE decreased the efficiency of the ADCC response. 2017 Journal of virology Abstract HIV H375S;H375S 60;31 65;50 28100618 Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. Filling this cavity with a histidine or tryptophan residue in Env with a natural serine residue at this position (S375H/W) increased the susceptibility of HIV-1-infected cells to ADCC. 2017 Journal of virology Abstract HIV S375H;S375W 114;114 121;121 Env 62 65 HIV infections 155 169 28100618 Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to the CD4-bound state. 2017 Journal of virology Abstract HIV S375H;S375W 89;89 96;96 gp120;gp120;Env 105;155;204 110;160;207 28107870 Identifications of drug resistance mutations among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia. RESULTS: DRMs were identified in 35% of patients, among which 46.7% of them showed minor resistance to protease inhibitor with A71V and L10l were the commonest DRMs detected. 2017 Asian Pacific journal of tropical medicine Abstract HIV A71V 127 131 PR 103 111 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. The distributions of M184V/I and M41L mutations differed significantly among three main HIV-1 genotypes identified. 2017 AIDS research and therapy Abstract HIV M184I;M184V;M41L 21;21;33 28;28;37 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. In general, DRMs were more common in subtype-C than in subtype-A and/or subtype-D (nucleoside reverse transcriptase inhibitor mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, and H221Y). 2017 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E138A;H221Y;K101E;K65R;Q151M;V106M;Y181C 168;200;189;136;145;175;182 173;205;194;140;150;180;187 NRTI;NNRTI 83;152 115;157 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. 2017 PloS one Abstract HIV K103N;K103S;M184V;M46I;M46L 64;64;83;102;102 71;71;88;108;108 RT;PR 33;132 54;140 28181034 HIV-1 genetic diversity and transmitted drug resistance frequency among Iranian treatment-naive, sexually infected individuals. All of the identified SDRMs belonged to the non-nucleoside reverse transcriptase inhibitors (NNRTIs) class, including K103 N and V106A, which were found in three patients. 2017 Archives of virology Abstract HIV K103N;V106A 118;129 124;134 NNRTI;NNRTI 44;93 80;99 28181034 HIV-1 genetic diversity and transmitted drug resistance frequency among Iranian treatment-naive, sexually infected individuals. Two minor HIV protease-inhibitor-related mutations (L10I and G73S) were detected in two patients, but these mutations are not included in the WHO SDRMs list. 2017 Archives of virology Abstract HIV G73S;L10I 61;52 65;57 PR 14 22 28195728 Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K. To better understand binding of clinical inhibitors to resistant HIV-1 protease, we used room-temperature joint X-ray/neutron (XN) crystallography to obtain an atomic-resolution structure of the protease triple mutant (V32I/I47V/V82I) in complex with amprenavir. 2017 Journal of medicinal chemistry Abstract HIV V32I;I47V;V82I 219;224;229 223;228;233 PR;PR 71;195 79;203 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. A comparison between pre-existing and emergent T97A patient populations (i.e., in the absence of primary INSTI RAMs) showed no significant differences in EVG or RAL susceptibility in vitro. 2017 PloS one Abstract HIV T97A 47 51 INSTI 105 110 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. During INSTI-based therapy, few patients experienced virologic failure with emergent INSTI RAMs (3%; 122 of 3881 patients), among whom T97A emerged infrequently in the presence (n = 6) or absence (n = 8) of primary INSTI RAMs. 2017 PloS one Abstract HIV T97A 135 139 INSTI;INSTI;INSTI 7;85;215 12;90;220 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Furthermore, among all T97A-containing viruses tested, only 38-44% exhibited reduced susceptibility to EVG and/or RAL (all of low magnitude; <11-fold), while all maintained susceptibility to dolutegravir. 2017 PloS one Abstract HIV T97A 23 38 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, detection of T97A does not affect response to INSTI-based therapy with EVG or RAL. 2017 PloS one Abstract HIV T97A 22 26 INSTI 55 60 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of the patients with pre-existing T97A, 17 had available clinical follow-up: 16 achieved virologic suppression and 1 maintained T97A and INSTI sensitivity without further resistance development. 2017 PloS one Abstract HIV T97A;T97A 34;128 38;132 INSTI 137 142 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Overall, T97A is an infrequent integrase polymorphism that is enriched among non-B HIV-1 subtypes and can confer low-level reduced susceptibility to EVG and/or RAL. 2017 PloS one Abstract HIV T97A 9 13 IN 31 40 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1.4%; 47 of 3367 integrase sequences); most often among non-B (5.3%) than B (0.9%) HIV-1 subtypes. 2017 PloS one Abstract HIV T97A 99 103 INSTI;INSTI;IN 9;38;147 14;43;156 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. 2017 PloS one Abstract HIV T97A 0 4 INSTI;IN;IN 93;17;56 98;26;65 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. These results suggest a very low risk of initiating INSTI-based therapy in patients with pre-existing T97A. 2017 PloS one Abstract HIV T97A 102 106 INSTI 52 57 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. 2017 PloS one Abstract HIV T97A 78 82 INSTI;INSTI 129;176 134;181 28234630 Prevalence of rilpivirine resistance in people starting antiretroviral treatment in Argentina. The most frequent mutations conferring resistance to rilpivirine were: E138A (n=6) and G190A (n=4). 2017 Antiviral therapy Abstract HIV E138A;G190A 71;87 76;92 28254696 Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization. Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). 2017 European journal of medicinal chemistry Abstract HIV E138K 107 112 28275184 RNA-Associated Early-Stage Antiviral Factor Is a Major Component of Lv2 Restriction. Further studies of the viral CA demonstrate that the CA mutation I73V (previously called I207V), a potent determinant for HIV-2, is a weak determinant of susceptibility for HIV-1. 2017 Journal of virology Abstract HIV I207V;I73V 89;65 94;69 Capsid;Capsid 29;53 31;55 28275184 RNA-Associated Early-Stage Antiviral Factor Is a Major Component of Lv2 Restriction. More potent CA determinants for HIV-1 REAF restriction were identified at P38A, N74D, G89V, and G94D. 2017 Journal of virology Abstract HIV G89V;G94D;N74D;P38A 86;96;80;74 90;100;84;78 Capsid 12 14 28275193 Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. We previously identified a disulfide bond, I201C-A433C (DS), which stabilizes Env in the vaccine-desired prefusion-closed state. 2017 Journal of virology Abstract HIV A433C;I201C 49;43 54;48 Env 78 81 28279801 Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness. Drug-resistance related mutations (DRMs) T369V/I and A371V in the connection subdomain (CN) of reverse transcriptase (RT) occur at higher frequencies in the individuals experiencing antiretroviral therapy failure. 2017 Virus research Abstract HIV A371V;T369I;T369V 53;39;39 58;48;48 RT;RT 95;118 116;120 28279801 Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness. Here, we evaluated the effects of T369V/I and A371V on viral fitness, in the presence or in the absence of thymidine analogue resistance-associated mutations (TAMs) and assessed the effect of potential RT structure-related mechanism on change in viral fitness. 2017 Virus research Abstract HIV A371V;T369I;T369V 46;34;34 51;41;41 RT 202 204 28279801 Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness. Mutations T369V/I, A371V, alone or in combination with TAMs were introduced into a modified HIV-1 infectious clone AT1 by site-directed mutagenesis. 2017 Virus research Abstract HIV A371V;T369I;T369V 19;10;10 24;17;17 28279801 Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness. Results showed that T369V/I severely impaired the relative virus fitness, and A371V compensated for the viral fitness reduction caused by TAMs. 2017 Virus research Abstract HIV A371V;T369I;T369V 78;20;20 83;27;27 28279801 Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness. Structural modeling of RT suggests that T369V/I substitutions disrupt powerful hydrogen bonds formed by T369 and V365 in p51 and p66. 2017 Virus research Abstract HIV T369I;T369V 40;40 47;47 RT 23 25 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. CONCLUSIONS: Characteristics frequently observed in CSF escape include HIV-1 infection >15 years, previous LLV, and M184V/I mutations in CSF. 2017 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 116;116 123;123 HIV infections 71 86 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. M184V/I mutations were identified in 74% of CSF samples when plasma levels were <=50 copies per milliliter. 2017 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 0;0 7;7 28328548 Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT. Three participants had TDF/FTC resistance (M184I, K65R), including 2 who received only 4 once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. 2017 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65R;M184I 50;43 54;48 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. K103N-harboring strains were introduced into the therapy-unexposed population via at least 6 independent transmissions epidemiologically linked to the surrounding countries. 2017 Clinical infectious diseases Abstract HIV K103N 0 5 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. NGS did not demonstrate additional minority K103N-variants compared to routine resistance testing. 2017 Clinical infectious diseases Abstract HIV K103N 44 49 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. The prevalence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) reached 45% (95% CI: 27-64%) in 2015, all based on the prevalence of mutation K103N. 2017 Clinical infectious diseases Abstract HIV K103N 167 172 NNRTI;NNRTI 32;81 68;87 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Virological failure of the WHO-recommended first-line NNRTI-based regimen was higher in the presence of K103N. 2017 Clinical infectious diseases Abstract HIV K103N 104 109 NNRTI 54 59 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. A different conformation of the beta3-beta4 hairpin loop in HIV-1 and HIV-2 RTs could probably explain the differential effects of K65R. 2017 Scientific reports Abstract HIV K65R 131 135 RT 76 79 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In HIV-2, resistance to all approved nucleoside analogues is conferred by the combination of RT substitutions K65R, Q151M and M184V. 2017 Scientific reports Abstract HIV K65R;M184V;Q151M 110;126;116 114;131;121 RT 93 95 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Interestingly, in highly divergent HIV-1 RTs, K65R confers several-fold increased accuracy of DNA synthesis. 2017 Scientific reports Abstract HIV K65R 46 50 RT 41 44 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Nucleotide incorporation kinetic analyses of mutant and wild-type (WT) HIV-2 RTs show that the triple-mutant has decreased catalytic efficiency due to the presence of M184V. 2017 Scientific reports Abstract HIV M184V 167 172 RT 77 80 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. We have determined the intrinsic fidelity of DNA synthesis of WT HIV-2 RT and mutants K65R and K65R/Q151M/M184V. 2017 Scientific reports Abstract HIV K65R;M184V;Q151M;K65R 95;106;100;86 99;111;105;90 RT 71 73 28333295 Drug resistance in antiretroviral-naive children newly diagnosed with HIV-1 in Manaus, Amazonas. The most common DRM was E138A (8.5%). 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138A 24 29 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. Naturally occurring, pseudoknot-insensitive viruses were rendered sensitive by the inverse K277R mutation, establishing RT as the genetic locus for aptamer-mediated HIV-1 inhibition. 2017 Nucleic acids research Abstract HIV K277R 91 96 RT 120 122 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. Viruses inhibited by pseudoknot aptamers were rendered insensitive by a naturally occurring R277K variant, providing the first demonstration of aptamer-specific resistance in cell culture. 2017 Nucleic acids research Abstract HIV R277K 92 97 28359840 SAMHD1 is active in cycling cells permissive to HIV-1 infection. Combination of three mutations (S18A, T21A, T25A) significantly prevented SAMHD1 phosphorylation but did not significantly affect HIV-1 replication in the presence of AZT. 2017 Antiviral research Abstract HIV S18A;T21A;T25A 32;38;44 36;42;48 28363735 Evolution of tenofovir-resistant HIV-1 isolates exposed to tenofovir alafenamide dose escalation. Resistance selection experiments using HIV-1 isolates harboring pre-existing tenofovir (TFV)-resistance (K65R, 3TAMs, and Q151M complex) were carried out with the novel tenofovir prodrug tenofovir alafenamide (TAF) as well as with tenofovir (TFV), to investigate the potential for additional resistance development in the presence of TAF or TFV. 2017 Antiviral research Abstract HIV K65R;Q151M 105;122 109;127 28363735 Evolution of tenofovir-resistant HIV-1 isolates exposed to tenofovir alafenamide dose escalation. Two new mutations were found during the selections (L429I, T69I) that were further characterized, and found to have very limited or no role in resistance to TAF or TFV. 2017 Antiviral research Abstract HIV L429I;T69I 52;59 57;63 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. 2017 EBioMedicine Abstract HIV A62V;K65N;K65R;K70E;K70Q;K70T;L74I;S68D;S68G;S68N;V75L;Y115F 38;44;44;62;62;62;72;52;52;52;78;88 42;50;50;70;70;70;76;60;60;60;82;93 NRTI 10 14 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. 2017 EBioMedicine Abstract HIV K65N;K65R;K70E;K70G;K70Q 68;68;82;82;82 74;74;90;90;90 28366604 Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses. Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity. 2017 Vaccine Abstract HIV N277A 41 46 gp160 55 60 28366604 Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses. Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively. 2017 Vaccine Abstract HIV N277A 19 24 28369593 Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. 2017 The Journal of antimicrobial chemotherapy Abstract HIV N155H 70 75 28369593 Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R. 2017 The Journal of antimicrobial chemotherapy Abstract HIV G118R;Q148K;Q148R 224;189;199 229;194;204 28369593 Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). 2017 The Journal of antimicrobial chemotherapy Abstract HIV A153G;A153S;A153S;G140A;G140S;N155H;Q148R;Q91R;Y143C;Y143G 126;126;150;171;171;118;163;198;190;142 133;133;155;178;178;123;168;202;195;147 28369593 Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response. In two of them N155H was replaced by Q148K/R and in another by G118R. 2017 The Journal of antimicrobial chemotherapy Abstract HIV G118R;N155H;Q148K;Q148R 63;15;37;37 68;20;44;44 28369593 Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response. Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. 2017 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Y143G 37;27 42;32 28369593 Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response. Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138A 29 34 28371730 Systematic profiling of substrate binding response to multidrug-resistant mutations in HIV-1 protease: Implication for combating drug resistance. In contrast, the key residue mutations N25D/D29N can completely eliminate (KD=n.d.) or largely reduce (KD=32 and 120muM, respectively) the binding capability of the two peptides, suggesting that these PR residues could be the potential target sites for developing resistance-free anti-HIV agents. 2017 Journal of molecular graphics & modelling Abstract HIV D29N;N25D 44;39 48;43 PR 201 203 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In treatment-experienced individuals, in contrast, rare cases of treatment failure were commonly associated with emergence of an R263K integrase substitution that confers low-level resistance to dolutegravir. 2017 mBio Abstract HIV R263K 129 134 IN 135 144 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In treatment-experienced individuals, the most frequent substitution associated with failure with dolutegravir is R263K in integrase. 2017 mBio Abstract HIV R263K 114 119 IN 123 132 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Prolonged infections with R263K mutant viruses led to less HIV-1 integrated DNA over time compared to wild-type viruses. 2017 mBio Abstract HIV R263K 26 31 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. R263K decreases integration both in cell-free and tissue culture assays. 2017 mBio Abstract HIV R263K 0 5 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The results show that R263K did not decrease reverse transcription. 2017 mBio Abstract HIV R263K 22 27 RT 45 66 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. These tissue culture results help to explain the absence of the R263K substitution in most individuals experiencing failure with DTG and support studies aiming at longitudinally measuring the levels of integrated DNA in individuals treated with this drug.IMPORTANCE Antiretroviral treatment decreases plasma viral RNA, but HIV DNA persists for decades within infected cells. 2017 mBio Abstract HIV R263K 64 69 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. To investigate a potential defect in reverse transcription with R263K, the levels of reverse transcripts were measured by quantitative PCR. 2017 mBio Abstract HIV R263K 64 69 RT 37 58 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. We investigated here how integrated DNA levels evolve over time during prolonged infections with R263K viruses. 2017 mBio Abstract HIV R263K 97 102 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. We report here that R263K progressively diminishes the levels of integrated HIV-1 DNA in tissue culture over multiple cycles of infection. 2017 mBio Abstract HIV R263K 20 25 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 95 99 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 86 90 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 0 4 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P< 0.001). 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 48 52 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 71 75 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R 14 18 NRTI 62 67 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K65R;K65R 26;89 30;93 NRTI 71 75 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. 2017 SAGE open medicine Abstract HIV E138A;M230L;Y181C 106;117;99 111;122;104 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. Drug resistance mutations were found in 121; 37 had L74V/I mutations, with 95% receiving abacavir (ABC)-containing regimens. 2017 The Pediatric infectious disease journal Abstract HIV L74I;L74V 52;52 58;58 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. L74V/I may be more prevalent than previously realized in children failing ABC-containing regimens, even when time on treatment has been short. 2017 The Pediatric infectious disease journal Abstract HIV L74I;L74V 0;0 6;6 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. L74V/I was associated with current ABC usage (P = 0.0001). 2017 The Pediatric infectious disease journal Abstract HIV L74I;L74V 0;0 6;6 28383402 Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice. We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. 2017 Medicine Abstract HIV M184V 100 106 28384058 Analysis of HIV Integrase Resistance in Black Men Who Have Sex with Men in the United States. The most frequently detected mutation was E157Q. 2017 AIDS research and human retroviruses Abstract HIV E157Q 42 47 28392143 Development of a DNA vaccine expressing a secreted HIV-1 gp41 ectodomain that includes the membrane-proximal external region. Two constructs (gp41 DeltaFP and gp41 DeltaFP+I682E) maintained binding by gp41 MPER-specific bnAbs (4E10, Z13e1 and 10E8). 2017 Vaccine Abstract HIV I682E 46 51 gp41;gp41;gp41 16;33;75 20;37;79 28396546 Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT). 2017 Antimicrobial agents and chemotherapy Abstract HIV A62V;F116Y;F77L;V75I;Q151M 37;59;49;43;0 41;64;53;47;5 28396546 Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. 2017 Antimicrobial agents and chemotherapy Abstract HIV Q151M 56 61 NRTI;RT 149;87 154;89 28396546 Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. 2017 Antimicrobial agents and chemotherapy Abstract HIV F116Y 58 63 28396546 Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations. 2017 Antimicrobial agents and chemotherapy Abstract HIV Q151M 20 25 28396546 Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. To understand the structural basis for Q151M and Q151Mc resistance, we systematically determined the crystal structures of the wild-type RT/double-stranded DNA (dsDNA)/dATP (complex I), wild-type RT/dsDNA/ddATP (complex II), Q151M RT/dsDNA/dATP (complex III), Q151Mc RT/dsDNA/dATP (complex IV), and Q151Mc RT/dsDNA/ddATP (complex V) ternary complexes. 2017 Antimicrobial agents and chemotherapy Abstract HIV Q151M;Q151M 39;225 44;230 RT;RT;RT;RT;RT 137;196;231;267;306 139;198;233;269;308 28402970 The Genotyping Resistance Profile of the Pol Gene Detected in Blood of Newly Diagnosed HIV-Positive Men Is Durably Archived in the Gut Whatever the Time of Initiation of cART. In 1 rilpivirine-treated patient, the M230I mutation was detected in PBMC. 2016 Intervirology Abstract HIV M230I 38 43 28402970 The Genotyping Resistance Profile of the Pol Gene Detected in Blood of Newly Diagnosed HIV-Positive Men Is Durably Archived in the Gut Whatever the Time of Initiation of cART. Those mostly detected were related to the resistance to nucleos(t)ide (D67N, L210W, T215A, T69D) and nonnucleoside (K103N, V106I, V179I) inhibitors. 2016 Intervirology Abstract HIV D67N;K103N;L210W;T215A;T69D;V106I;V179I 71;116;77;84;91;123;130 75;121;82;89;95;128;135 28443724 Genetic Diversity of HIV-1 Gene vif Among Treatment-Naive Brazilians. In this study, we explored the correlations of Vif polymorphisms with clinical parameters of the patients and found that mutation K22H is associated with low CD4+ cell counts and higher viral loads. 2017 AIDS research and human retroviruses Abstract HIV K22H 130 134 Vif 47 50 28453836 Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide. At least 1 thymidine-analogue mutations was present in 2.7% of patients with 0.07% harboring T215Y/F and 2.7% harboring T215 revertant mutations (T215rev). 2017 The Journal of infectious diseases Abstract HIV T215F;T215Y 93;93 100;100 28453836 Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide. Only 1 patient had K65R (0.01%) and 7 had M184V/I (0.1%), despite high use of tenofovir disoproxil fumarate (TDF), emtricitabine, and lamivudine and potential transmission of resistance to these drugs. 2017 The Journal of infectious diseases Abstract HIV K65R;M184I;M184V 19;42;42 23;49;49 28453836 Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide. Patients with the combination of M41L + L210W + T215rev showed full human immunodeficiency virus RNA suppression while receiving a TDF- or tenofovir alafenamide-containing regimen. 2017 The Journal of infectious diseases Abstract HIV L210W;M41L 40;33 45;37 28453836 Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide. Results: The presence of TDRMs increased during this period (from 5.2% to 11.4%), primarily driven by an increase in nonnucleoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations (from 0.3% to 7.1%), particularly K103N/S (increase from 0.3% to 5.3%). 2017 The Journal of infectious diseases Abstract HIV K103N;K103S 231;231 238;238 NNRTI;NNRTI;RT 117;169;154 152;174;156 28458918 Transmission fitness of drug-resistant HIV revealed in a surveillance system transmission network. Decreased transmission fitness was demonstrated for twenty-three mutations, including M184V. 2017 Virus evolution Abstract HIV M184V 86 91 28458918 Transmission fitness of drug-resistant HIV revealed in a surveillance system transmission network. K103N, Y181C, and L90M) had transmission fitness that was indistinguishable from or exceeded wild-type fitness, permitting the establishment of large, self-sustaining drug resistance reservoirs. 2017 Virus evolution Abstract HIV L90M;Y181C;K103N 18;7;0 22;12;5 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. Newly synthesized p-cyanovinyl-DAANs (8a-8g) with different R1 side chains plus prior active p-cyanoethyl-DAANs (4a-4c) were evaluated not only for anti-HIV potency against both wild-type HIV virus and rilpivirine-resistant (E138K, E138K+M184I) viral replication, but also for multiple drug-like properties, including aqueous solubility, lipophilicity, and metabolic stability in human liver microsomes and human plasma. 2017 Bioorganic & medicinal chemistry letters Abstract HIV E138K;E138K;M184I 225;232;238 230;237;243 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. This study revealed that both ester and amide R1 substituents led to low nanomolar anti-HIV potency against wild-type and rilpivirine-resistant viral strains (E138K-resistance fold changes<3). 2017 Bioorganic & medicinal chemistry letters Abstract HIV E138K 159 164 28468838 HIV-1 Tat potently stabilises Mdm2 and enhances viral replication. Furthermore, the non-phosphorylatable mutant of Mdm2 (S166A) is unable to support HIV-1 replication. 2017 The Biochemical journal Abstract HIV S166A 54 59 28468838 HIV-1 Tat potently stabilises Mdm2 and enhances viral replication. Moreover, the non-phosphorylatable mutant of Mdm2 (S166A) fails to interact with Tat and shows decreased half-life in the presence of Tat compared with wild-type Mdm2. 2017 The Biochemical journal Abstract HIV S166A 51 56 Tat;Tat 81;134 84;137 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. With dolutegravir, large cluster HIV-1 variants acquired solitary R263K ( n= 7), S153Y ( n= 1) or H51Y ( n= 1) mutations as the dominant quasi-species within 8-12 weeks as compared with small cluster lineages where R263K ( n= 1/6), S153Y (1/6) or WT species (4/6) were observed after 24 weeks. 2017 The Journal of antimicrobial chemotherapy Abstract HIV H51Y;R263K;R263K;S153Y;S153Y 98;66;215;81;232 102;71;220;86;237 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. With elvitegravir, large cluster variants more rapidly acquired first mutations (T66I, A92G, N155H or S147G) by week 8 followed by sequential accumulation of multiple mutations leading to viral escape (>10 muM) by week 24. 2017 The Journal of antimicrobial chemotherapy Abstract HIV A92G;N155H;S147G;T66I 87;93;102;81 91;98;107;85 28481112 Structure-Based Optimization of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with Improved Potency against Resistance-Associated Variants. Compound 25a was exceptionally potent against the whole viral panel, affording 3-4-fold enhancement of in vitro antiviral potency against WT, L100I, K103N, Y181C, Y188L, E138K, and K103N+Y181C and 10-fold enhancement against F227L+V106A relative to the reference drug etravirine (ETV) in the same cellular assay. 2017 Journal of medicinal chemistry Abstract HIV E138K;F227L;K103N;K103N;L100I;V106A;Y181C;Y181C;Y188L 170;225;149;181;142;231;156;187;163 175;230;154;186;147;236;161;192;168 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. In this study, HIV-1 infected patients (n = 120) from North India revealed Ser46Phe (20%) and Ser61Arg (2%) mutations in the Tat variants with a strong interaction toward TAR leading to enhanced transactivation activities. 2017 Frontiers in microbiology Abstract HIV S46F;S61R 75;94 83;102 Tat 125 128 HIV infections 15 29 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Molecular dynamics simulation data verified that the variants with this mutation had a higher binding affinity for TAR than both the wild-type Tat and other variants that lacked Ser46Phe and Ser61Arg. 2017 Frontiers in microbiology Abstract HIV S46F;S61R 178;191 186;199 Tat 143 146 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. L63P and M184V were the dominant mutations observed for the protease (PRO) and reverse transcriptase (RT) encoding genes, respectively. 2017 PloS one Abstract HIV M184V;L63P 9;0 14;4 RT;PR;RT 79;60;102 100;68;104 28494325 HIV-1 integrase inhibitor resistance among treatment naive patients in the West of Scotland. RESULTS: We detected integrase inhibitor resistance (T66I/T) at baseline in one patient sample. 2017 Journal of clinical virology Abstract HIV T66I;T66T 53;53 59;59 IN 21 30 28507107 In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150, Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical Development for the Prevention of HIV-1 Infection. However, MIV-150 genital tract concentrations may be insufficient to inhibit many resistant viruses, including those harboring K103N or Y181C. 2017 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C 127;136 132;141 28520611 Treatment Outcomes of Third-line Antiretroviral Regimens in HIV-infected Thai Adolescents. Genotypes at time of second-line failure (n = 44) were M184V (77%), >=4 thymidine analogue mutations (25%), non-nucleoside reverse transcriptase inhibitor-resistant associated mutation (RAM) (80%), ETR-RAM score >=4 (14%), any lopinavir-RAM (59%) and >=1 major DRV-RAM (41%). 2017 The Pediatric infectious disease journal Abstract HIV M184V 55 60 NNRTI 108 144 28521719 Virological Suppression and Patterns of Resistance Amongst Patients on Antiretroviral Therapy at 4 Nigerian Military Hospitals. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations (K103N or Y188C). 2017 Current HIV research Abstract HIV K103N;M184V;Y188C 176;93;185 182;98;190 NNRTI;NNRTI 110;158 146;163 28525359 I36T upward arrowT mutation in South African subtype C (C-SA) HIV-1 protease significantly alters protease-drug interactions. This variant PR harbours a mutation and insertion (I36T T) at position 36 of the C-SA HIV-1 PR, and did not show a significant difference in the catalytic effect of the HIV-1 PR. 2017 Biological chemistry Abstract HIV I36T 51 56 PR;PR;PR 13;92;175 15;94;177 28533248 Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors. A novel HIV-1 integrase mutation pattern, L74F V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. 2017 Antimicrobial agents and chemotherapy Abstract HIV L74F;V75I 42;47 46;51 IN;IN;INSTI 14;100;138 23;109;144 28533248 Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors. Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153- and 197-fold, respectively). 2017 Antimicrobial agents and chemotherapy Abstract HIV G140S;L74F;N155H;Q148H;V75I 34;12;25;40;17 39;16;30;45;21 INSTI 99 105 28539254 Transmitted drug resistance in patients with acute/recent HIV infection in Brazil. The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. 2017 The Brazilian journal of infectious diseases Abstract HIV K103N 128 133 NNRTI 75 111 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. Six-percent (n=6) had at least one HIVDR mutation, comprising NRTI-associated mutations, (M184V, T69D, T69N and V75I); NNRTI-associated mutations (G190A, K103N, V106M, Y181C) and thymidine analogue associated mutations (D67N, K70R, K219Q, L210W, M41L, T215Y). 2017 The open microbiology journal Abstract HIV D67N;G190A;K103N;K219Q;K70R;L210W;M184V;M41L;T215Y;T69D;T69N;V106M;V75I;Y181C 220;147;154;232;226;239;90;246;252;97;103;161;112;168 224;152;159;237;230;244;95;250;257;101;107;166;116;173 NNRTI;NRTI 119;62 124;66 28566227 Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial. INTERPRETATION: After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. 2017 The lancet. HIV Abstract HIV M184V 238 243 PR;PR;NRTI 53;135;77 61;143;81 28566227 Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per muL, adherence of at least 90%, and no change to ART in the past 3 months. 2017 The lancet. HIV Abstract HIV M184V 81 86 NRTI;PR;NRTI 175;147;220 207;155;224 HIV infections 32 46 28576126 Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee. However, initial lack of adherence and/or differences in pharmacokinetics led to low plasma drug concentrations, which resulted in transient rebound viremia and the emergence of FTC resistance mutations (M184V/I) identical to those observed in HIV-1 infected humans. 2017 Retrovirology Abstract HIV M184I;M184V 204;204 211;211 HIV infections 244 258 28589513 Prevalence of HIV-1 transmitted drug resistance in recently infected, treatment-naive persons in the Southwest of Iran, 2014-2015. Two participants had non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, specifically K103N in one individual and K101EK/K103KN/G190AG in the other. 2017 Archives of virology Abstract HIV G190A;G190G;K101E;K101K;K103K;K103N;K103N 153;153;139;139;146;146;111 159;159;145;145;152;152;116 NNRTI;NNRTI 69;21 74;57 28604824 Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. 2017 PloS one Abstract HIV M184V 261 266 28604824 Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. MATERIALS & METHODS: Participants with documented nonadherence, M184V mutation, CD4+ T cell count >=100 cells/mm3 and VF (HIV-1 plasma RNA >=400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. 2017 PloS one Abstract HIV M184V 64 69 28604824 Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. 2017 PloS one Abstract HIV M184V 89 94 28604824 Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. switching to 3TC/FTC as a "bridging strategy" to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. 2017 PloS one Abstract HIV M184V 118 123 28610923 L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase. Accordingly, M178I mutant of IN failed to interact with IBD. 2017 Biochemical and biophysical research communications Abstract HIV M178I 13 18 IN 29 31 28610923 L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase. In contrast to alanine substitution, L368F mutation showed a ~25% decrease, while V408L and V408F showed wild type binding, to IN. 2017 Biochemical and biophysical research communications Abstract HIV L368F;V408F;V408L 37;92;82 42;97;87 IN 127 129 28610923 L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase. Interestingly, a L368F/V408F double mutant of IBD restored binding to M178I mutant of IN, indicating that altered hydrophobicity in the inter helical loops of IBD might make I365 more accessible for interaction with IN. 2017 Biochemical and biophysical research communications Abstract HIV L368F;M178I;V408F 17;70;23 22;75;28 IN;IN 86;216 88;218 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. 31 DRMs were identified from 27 samples including four protease inhibitors (PIs) accessory DRMs, two PIs major DRMs (M46I), two nucleoside RT inhibitors DRMs (K219R and K70Q), and 23 nonnucleoside RT inhibitors DRMs. 2017 PloS one Abstract HIV K219R;K70Q;M46I 159;169;117 165;173;121 PI;PI;PR;RT;RT 76;101;55;139;197 79;104;63;141;199 28623781 Inhibition activities of catechol diether based non-nucleoside inhibitors against the HIV reverse transcriptase variants: Insights from molecular docking and ONIOM calculations. The binding efficacies of the inhibitors are significantly suppressed by the Y181C and K103N mutations, as revealed by the computed interaction energies at the ONIOM [B3LYP/6-31G(d,p):PM6] level of theory. 2017 Journal of molecular graphics & modelling Abstract HIV K103N;Y181C 87;77 92;82 28627486 The association between detected drug resistance mutations and CD4(+) T-cell decline in HIV-positive individuals maintained on a failing treatment regimen. Among individuals with at least one DRM, we found evidence that any nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance, the reverse transcriptase (RT) mutations M184V, D67N and T215Y as well as the protease mutations V82A and I54V were associated with reduced CD4 declines. 2018 Antiviral therapy Abstract HIV D67N;I54V;M184V;T215Y;V82A 189;247;182;198;238 193;251;187;203;242 RT;RT;PR;NRTI;RT 90;145;219;123;168 111;166;227;127;170 28627486 The association between detected drug resistance mutations and CD4(+) T-cell decline in HIV-positive individuals maintained on a failing treatment regimen. The detection of any non-nucleoside reverse transcriptase inhibitor resistance, the RT mutations V179D and L74V were associated with steeper CD4 declines. 2018 Antiviral therapy Abstract HIV L74V;V179D 107;97 111;102 NNRTI;RT 21;84 57;86 28628334 Chiral Indolylarylsulfone Non-Nucleoside Reverse Transcriptase Inhibitors as New Potent and Broad Spectrum Anti-HIV-1 Agents. The new IASs 8-37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N-Y181C HIV-1 strains. 2017 Journal of medicinal chemistry Abstract HIV K103N;K103N;Y181C;Y181C;Y188L 90;115;97;121;104 95;120;102;126;109 28637235 Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice. The virus from this mouse had mutations E138K, G140S, Q148H, N155H and S230R, was highly resistant to both raltegravir (EC50 of >1000 nM) and dolutegravir (EC50 of 550 nM), and replicated to levels similar to those of control viruses in PBMCs. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;G140S;N155H;Q148H;S230R 40;47;61;54;71 45;52;66;59;76 28637235 Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice. Viruses from raltegravir failing mice developed mutations G140G/S and Q148H/K, and were resistant to both raltegravir (EC50 values of >100 nM) and dolutegravir (EC50 values ranging from 8.8 to 13.3 nM). 2017 The Journal of antimicrobial chemotherapy Abstract HIV G140G;G140S;Q148H;Q148K 58;58;70;70 65;65;77;77 28640909 HIV-Tat regulates macrophage gene expression in the context of neuroAIDS. The K50A Tat-mutation dysregulated expression of these genes without affecting the binding of the Tat complex to their gene sequences. 2017 PloS one Abstract HIV K50A 4 8 Tat;Tat 9;98 12;101 28641707 Analysis of transmitted HIV drug resistance from 2005 to 2015 in Victoria, Australia: a comparison of the old and the new. Compared with 2005-10, during 2011-15 there was a significant decline in the prevalence of the non-nucleoside-associated mutation K103N and the nucleoside-associated mutations at codons M41 and T215. 2017 Sexual health Abstract HIV K103N 130 135 28641707 Analysis of transmitted HIV drug resistance from 2005 to 2015 in Victoria, Australia: a comparison of the old and the new. One patient was detected with a major INI resistance mutation, namely G118R. 2017 Sexual health Abstract HIV G118R 70 75 IN 38 41 28645089 Drug Resistance Mechanism of L10F, L10F/N88S and L90M mutations in CRF01_AE HIV-1 protease: Molecular dynamics simulations and binding free energy calculations. In this work, we examined the effect of non active site mutations L10F, L10F/N88S and L90M with nelfinavir using molecular dynamics simulation and binding free energy calculations. 2017 Journal of molecular graphics & modelling Abstract HIV L10F;L10F;L90M;N88S 66;72;86;77 70;76;90;81 28645089 Drug Resistance Mechanism of L10F, L10F/N88S and L90M mutations in CRF01_AE HIV-1 protease: Molecular dynamics simulations and binding free energy calculations. Our present study shed light on the resistance mechanism of the strongly linked mutation L10F/N88S observed experimentally in AE subtype. 2017 Journal of molecular graphics & modelling Abstract HIV L10F;N88S 89;94 93;98 28645089 Drug Resistance Mechanism of L10F, L10F/N88S and L90M mutations in CRF01_AE HIV-1 protease: Molecular dynamics simulations and binding free energy calculations. The benzamide moiety of nelfinavir shows large positional deviation in L10F and L10F/N88S complexes and the L10F/N88S mutation changes the hydrogen bond between the side chain atoms of 30th residue and the 88th residue. 2017 Journal of molecular graphics & modelling Abstract HIV L10F;L10F;L10F;N88S;N88S 71;80;108;113;85 75;84;112;117;89 28645089 Drug Resistance Mechanism of L10F, L10F/N88S and L90M mutations in CRF01_AE HIV-1 protease: Molecular dynamics simulations and binding free energy calculations. The simulations suggested that the L10F and L10F/N88S mutants decrease the binding affinity of nelfinavir, whereas the L90M mutant increases the binding affinity. 2017 Journal of molecular graphics & modelling Abstract HIV L10F;L10F;L90M;N88S 35;44;119;49 39;48;123;53 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. PI mutations detected were M46I (n=1, 0.9%) and L90M (n=1, 0.9%). 2017 Infection ecology & epidemiology Abstract HIV L90M;M46I 48;27 52;31 PI 0 2 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. Six patients harbouring T215C/D, were linked in a supported phylogenetic cluster. 2017 Infection ecology & epidemiology Abstract HIV T215C;T215D 24;24 31;31 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The most frequent NRTI mutation detected was T215C/D (n=7, 5.7%). 2017 Infection ecology & epidemiology Abstract HIV T215C;T215D 45;45 52;52 NRTI 18 22 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The only NNRTI mutation detected was K103N (n=1, 0.9%). 2017 Infection ecology & epidemiology Abstract HIV K103N 37 42 NNRTI 9 14 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. E138X-containing HIV-1 variants were assessed for in-vitro replication as a surrogate of mutation stability following transmission. 2017 AIDS (London, England) Abstract HIV E138X 0 5 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing human leukocyte antigen (HLA)-B18 where reverse transcriptase-E138X arises as an immune escape mutation. 2017 AIDS (London, England) Abstract HIV E138X;E138X 78;235 83;240 RT;RT 45;213 66;234 HIV infections 118 132 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. METHODS: We analyzed linked reverse transcriptase-E138X/HLA data from 7772 antiretroviral-naive patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global reverse transcriptase-E138X and HLA frequencies from public databases. 2017 AIDS (London, England) Abstract HIV E138A;E138H;E138L;E138X;E138X 50;50;50;50;219 57;57;57;57;224 RT;RT 28;197 49;218 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Notably, reverse transcriptase-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. 2017 AIDS (London, England) Abstract HIV E138X 31 36 RT 9 30 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Regional reverse transcriptase-E138X surveillance should be undertaken before use of rilpivirine PrEP. 2017 AIDS (London, England) Abstract HIV E138X 31 36 RT 9 30 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. RESULTS: Reverse transcriptase-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B18-positive individuals globally (P = 3.5 x 10) and in all HIV-1 subtypes except A. 2017 AIDS (London, England) Abstract HIV E138A;E138G;E138K;E138X 118;118;118;31 127;127;127;36 RT 9 30 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X and B18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman's R = 0.75; P = 7.6 x 10) and in unlinked HIV/HLA data from 43 countries (Spearman's R = 0.34, P = 0.02). 2017 AIDS (London, England) Abstract HIV E138X 22 27 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. This, along with the observation that reverse transcriptase-E138X variants do not confer in-vitro replicative costs, supports their persistence, and ongoing accumulation in circulation over time. 2017 AIDS (London, England) Abstract HIV E138X 60 65 RT 38 59 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. We investigate the global prevalence, B18-linkage and replicative cost of reverse transcriptase-E138X and its regional implications for rilpivirine PrEP. 2017 AIDS (London, England) Abstract HIV E138X 96 101 RT 74 95 28659324 Multimethod Longitudinal HIV Drug Resistance Analysis in Antiretroviral-Therapy-Naive Patients. ART-naive HIV-1-infected patients from Cameroon were subjected to a multimethod HIVDR analysis using amplification-refractory mutation system (ARMS)-PCR, Sanger sequencing, and longitudinal next-generation sequencing (NGS) to determine their profiles for the mutations K103N, Y181C, K65R, M184V, and T215F/Y. 2017 Journal of clinical microbiology Abstract HIV K103N;K65R;M184V;T215F;T215Y;Y181C 269;283;289;300;300;276 274;287;294;307;307;281 HIV infections 10 24 28659324 Multimethod Longitudinal HIV Drug Resistance Analysis in Antiretroviral-Therapy-Naive Patients. Using Sanger sequencing, the overall prevalence of HIVDR mutations was 7.6% (5/66) and included all studied mutations except K65R. 2017 Journal of clinical microbiology Abstract HIV K65R 125 129 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. CONCLUSION: The case reported provides clinical support of previous findings that show that the R77Q and Q3R HIV-1 Vpr variants are associated with patients with delayed disease progression. 2014 JMM case reports Abstract HIV Q3R;R77Q 105;96 108;100 Vpr 115 118 28679441 HIV-1 genetic diversity and primary drug resistance mutations before large-scale access to antiretroviral therapy, Republic of Congo. Two samples (4%) harboring the mutations M230L and Y181C associated with the TAMs M41L and T215Y, respectively, were found. 2017 BMC research notes Abstract HIV M230L;M41L;T215Y;Y181C 41;82;91;51 46;86;96;56 28688977 Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. 2017 Infection, genetics and evolution Abstract HIV E138A;E138Q;K103N;V179D 60;74;67;80 65;79;72;85 28688977 Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions. The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. 2017 Infection, genetics and evolution Abstract HIV E138A;E138Q;K103N;V179D 106;120;113;127 111;125;118;132 NNRTI 78 83 28688977 Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions. The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). 2017 Infection, genetics and evolution Abstract HIV E138A;E138Q;K103N;V179D 60;74;88;105 65;79;93;110 NNRTI 29 34 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. E212A/L213A substitutions decreased the integrase capacity to bind Ku70 in HEK293T cells. 2017 Scientific reports Abstract HIV E212A;L213A 0;6 5;11 IN 40 49 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. Single substitutions within integrase (E212A or L213A) block the interaction with Ku70 thus indicating that the binding site formed by the 200-220 a.a. 2017 Scientific reports Abstract HIV E212A;L213A 39;48 45;53 IN 28 37 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. 2017 PLoS pathogens Abstract HIV N74D 99 103 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. 2017 PLoS pathogens Abstract HIV N74D 193 197 Capsid 206 212 28732792 Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013-2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. 2017 Journal of global antimicrobial resistance Abstract HIV E138A 135 140 NNRTI 189 194 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha). 2017 Scientific reports Abstract HIV S75X 124 128 PI 265 267 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. 2017 Scientific reports Abstract HIV S75X 133 137 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. In addition, the protease inhibitor drug resistance mutations I54V and V82A were identified for the first time in Shandong Province. 2017 PloS one Abstract HIV I54V;V82A 62;71 66;75 PR 17 25 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. M184V was the most frequently found point mutation, conferring resistance to the nucleoside reverse transcriptase inhibitor, while Y181C, G190A, K103N and V179D/E/F were the most frequent point mutations conferring resistance to the non-nucleoside reverse transcriptase inhibitor. 2017 PloS one Abstract HIV G190A;K103N;V179D;V179E;V179F;Y181C;M184V 138;145;155;155;155;131;0 143;150;164;164;164;136;5 NNRTI;NRTI 233;81 269;113 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The most common DRMs were; M184V (51.7%), K103N (50%), V106M (20.6%), D67N (13.3%), K65R (12%). 2017 AIDS research and therapy Abstract HIV D67N;K103N;K65R;M184V;V106M 70;42;84;27;55 74;47;88;32;60 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The proportion of DRM in RNA and DNA were mostly similar with the exception of the thymidine analogue mutations (TAMs) D67N, K70R, K219QE; and K103N which were slightly more prevalent in DNA than RNA. 2017 AIDS research and therapy Abstract HIV D67N;K103N;K219E;K219Q;K70R 117;143;131;131;125 123;148;137;137;129 28795354 Drug resistance mutation profiles of the drug-naive and first-line regimen-treated HIV-1-infected population of Suzhou, China. Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. 2017 Virologica Sinica Abstract HIV K70E;K70N;L76V;V179D;V179E 36;36;5;47;47 42;42;9;54;54 RT 98 100 28795354 Drug resistance mutation profiles of the drug-naive and first-line regimen-treated HIV-1-infected population of Suzhou, China. Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region. 2017 Virologica Sinica Abstract HIV K70E;K70N;L33F;L76V;V179D;V179E 126;126;78;87;137;137 133;133;83;91;144;144 PR;RT 100;153 108;155 28797181 HIV Resistance and Prevention of Mother-to-Child Transmission Regimen in HIV-Infected Infants in Northern Tanzania. The most common HLRMs to NVP were K103 N, Y181C, and Y188 L. 2017 AIDS research and human retroviruses Abstract HIV K103N;Y181C;Y188L 34;42;53 40;47;59 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. The most abundant, albeit, minor-frequency RT TDRM, were the K65R and D67N, while K103N, M184V and T215S were high-frequency mutations. 2017 Journal of the International AIDS Society Abstract HIV D67N;K103N;K65R;M184V;T215S 70;82;61;89;99 74;87;65;94;104 RT 43 45 28802032 Deciphering critical amino acid residues to modify and enhance the binding affinity of ankyrin scaffold specific to capsid protein of human immunodeficiency virus type 1. However, vdW calculation preconized to substitute serine for tyrosine at position 45. 2018 Asian Pacific journal of allergy and immunology Abstract HIV Y45S 50 84 28802032 Deciphering critical amino acid residues to modify and enhance the binding affinity of ankyrin scaffold specific to capsid protein of human immunodeficiency virus type 1. Remarkably, the affinity for the viral CA was significantly enhanced in AnkGAG1D4-S45Y mutant, with no alteration of the target specificity. 2018 Asian Pacific journal of allergy and immunology Abstract HIV S45Y 82 86 Capsid 39 41 28814231 HIV Type 1 Integrase Natural Polymorphisms in Viral Variants Circulating in FSU Countries. The prevalence of minor/ accessory substitutions depended on HIV-1 variants, while the most notable findings were L74I in subtype A6 (93.1%) and E157Q in subtype B (44.0%). 2017 Current HIV research Abstract HIV E157Q;L74I 145;114 150;118 28827354 Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography. Resistance associated with the Tyr181Cys mutation in HIV-1 RT has been a key roadblock in the discovery of nonnucleoside RT inhibitors (NNRTIs). 2017 Proc Natl Acad Sci U S A Abstract HIV Y181C 31 40 NNRTI;RT;RT 136;59;121 142;61;123 28827354 Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography. We report covalent inhibitors of Tyr181Cys RT (CRTIs) that can completely knock out activity of the resistant mutant and of the particularly challenging Lys103Asn/Tyr181Cys variant. 2017 Proc Natl Acad Sci U S A Abstract HIV K103C;K103N;K103Y;Y181C;Y181C 153;153;153;163;33 162;162;162;172;42 RT 43 45 28832412 The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro. Phenotypic analysis showed that E157Q results in minimal changes in RAL and DTG susceptibility. 2017 AIDS (London, England) Abstract HIV E157Q 32 37 28832412 The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro. Six recombinant viruses were constructed containing integrase from clinical HIV-1 isolates found to harbour E157Q as the only integrase strand inhibitor (INSTI) resistance-related mutation. 2017 AIDS (London, England) Abstract HIV E157Q 108 113 IN;IN;INSTI 52;126;154 61;135;159 28832412 The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro. The HIV-1 integrase E157Q natural polymorphism has been reported to cause one case of raltegravir (RAL) and dolutegravir (DTG) failure. 2017 AIDS (London, England) Abstract HIV E157Q 20 25 IN 10 19 28832412 The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro. The previously reported case of E157Q-based resistance must have resulted from combined as yet unidentified integrase polymorphisms. 2017 AIDS (London, England) Abstract HIV E157Q 32 37 IN 108 117 28832412 The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro. Together with data retrieved from the Stanford HIV database, our results indicate that E157Q is not a relevant INSTI resistance mutation per se. 2017 AIDS (London, England) Abstract HIV E157Q 87 92 INSTI 111 116 28835492 HIV-1 Resistance to Dolutegravir Is Affected by Cellular Histone Acetyltransferase Activity. Although no detectable differences in the levels of cell-free acetylation of the wild-type (WT) and mutated R263K enzymes were observed, the inhibition of cellular histone acetyltransferase enzymes sensitized the NL4.3WT virus to DTG, while NL4.3R263K was almost completely unaffected. 2017 Journal of virology Abstract HIV R263K;R263K 246;108 251;113 28835492 HIV-1 Resistance to Dolutegravir Is Affected by Cellular Histone Acetyltransferase Activity. Here we report that regulation of the acetylation of integrase is integral to the replication of HIV in the presence of DTG and that the R263K mutation specifically disrupts this regulation, likely due to enhancement of interactions with the histone deacetylase I complex, as suggested by coimmunoprecipitation assays. 2017 Journal of virology Abstract HIV R263K 137 142 IN 53 62 28835492 HIV-1 Resistance to Dolutegravir Is Affected by Cellular Histone Acetyltransferase Activity. However, resistance against the newest integrase inhibitor, dolutegravir (DTG), is associated with an R263K substitution at the C terminus of integrase that causes resistance through an unknown mechanism. 2017 Journal of virology Abstract HIV R263K 102 107 IN;IN 39;142 48;151 28835492 HIV-1 Resistance to Dolutegravir Is Affected by Cellular Histone Acetyltransferase Activity. When levels of endogenous acetylation were manipulated in virus-producing cells, inhibitors of acetylation enhanced the replication of NL4.3R263K, whereas inhibition of deacetylation greatly diminished the replication of NL4.3WT Taken together, these results point to a pivotal role of acetylation in the resistance mechanism of HIV to some second-generation integrase strand transfer inhibitors, such as DTG.IMPORTANCE This is, to our knowledge, the first report of the influence of posttranslational modifications on HIV drug resistance. 2017 Journal of virology Abstract HIV R263K 140 145 IN 359 368 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. Natural mutant Ser46Phe in the core motif could likely led to conformational change resulting in more hydrogen bond interactions than the wild type Tat making it highly potent transactivator. 2017 Frontiers in microbiology Abstract HIV S46F 15 23 Tat 148 151 28859311 Design, synthesis and antiviral evaluation of novel heteroarylcarbothioamide derivatives as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and RDDP functions. Site-directed mutagenesis experiments showed that, with respect to wt RT, V108A substitution strongly reduced A15 IC50 values (12.6-fold for RNase H inhibition and 4.7-fold for RDDP), while substitution A502F caused a 9.0-fold increase in its IC50 value for RNase H, not affecting the RDDP inhibition, reinforcing the hypothesis of a dual-site inhibition. 2017 Pathogens and disease Abstract HIV A502F;V108A 203;74 208;79 RT 70 72 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). A62V, V90I, K103N, or E138A/G/K/Q; 68-82%) demonstrated virologic suppression at week 48, with no resistance development except for one patient with M184V and pre-existing K103N in the ATV + RTV + FTC/TDF group. 2017 HIV clinical trials Abstract HIV E138A;E138G;E138K;E138Q;K103N;K103N;M184V;V90I;A62V 22;22;22;22;12;172;149;6;0 33;33;33;33;17;177;154;10;4 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Emergent resistance was rare (0% EVG/COBI/FTC/TDF; 1% ATV + RTV + FTC/TDF - 3 with M184V/I in RT). 2017 HIV clinical trials Abstract HIV M184I;M184V 83;83 90;90 RT 94 96 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Pre-existing mutations did not lead to virologic failure; most with the polymorphic primary IN substitution T97A (92%), or with substitutions in RT. 2017 HIV clinical trials Abstract HIV T97A 108 112 IN;RT 92;145 94;147 28899102 Community Based Antiretroviral Treatment in Rural Zimbabwe. Seven participants had sequence data available, and five had drug resistance mutations, K65R, T69N, K101E, K103N, Y181C/I, M184V, and G190A. 2017 AIDS research and human retroviruses Abstract HIV G190A;K101E;K103N;K65R;M184V;T69N;Y181C;Y181I 134;100;107;88;123;94;114;114 139;105;112;92;128;98;121;121 28923862 Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1. In both single and multiple rounds of HIV-1 infections, BIC remained active against the Y143R, N155H, R263K, R263K/M50I, and R263K/E138K mutants (<=4-fold increase in EC50). 2017 Antimicrobial agents and chemotherapy Abstract HIV E138K;M50I;N155H;R263K;R263K;R263K;Y143R 131;115;95;102;109;125;88 136;119;100;107;114;130;93 28923862 Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1. In multiple rounds of infection, the G140S/Q148H combination of substitutions decreased HIV-1 susceptibility to BIC 4.8-fold compared to 16.8- and 7.4-fold for CAB and DTG, respectively. 2017 Antimicrobial agents and chemotherapy Abstract HIV G140S;Q148H 37;43 42;48 28923862 Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1. In single cycle SIV infections, none of the E92Q, T97A, Y143R, or N155H substitutions had a significant effect on susceptibility to BIC (<=4-fold increase in EC50), whereas G118R and R263K conferred ~14-fold and ~6-fold increases in EC50, respectively. 2017 Antimicrobial agents and chemotherapy Abstract HIV E92Q;G118R;N155H;R263K;T97A;Y143R 44;173;66;183;50;56 48;178;71;188;54;61 28942522 HIV-1 genetic diversity, geographical linkages and antiretroviral drug resistance among individuals from Pakistan. The remaining 7% of the sequences contained a major mutation, Y115F, which causes the virus to exhibit low to intermediate resistance against lamivudine and emtricitabine. 2018 Archives of virology Abstract HIV Y115F 62 67 28954995 Generation and characterization of new CCR5-tropic HIV-1rmt clones. We further constructed their variant clones bearing N160K, S304G, or G310R mutation in Env that potentially can change the viruses to better grow. 2017 The journal of medical investigation Abstract HIV G310R;N160K;S304G 69;52;59 74;57;64 Env 87 90 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Furthermore, the viruses produced from cells expressing the D256R/K260E/K263E/E267R mutant restored tRNALys3 packaging efficiency because the mutant exerted a dominant negative effect by preventing WT GAPDH from binding to MA and CA-NTD and improved the reverse transcription. 2016 Biochemistry and biophysics reports Abstract HIV D256R;E267R;K260E;K263E 60;78;66;72 65;83;71;77 RT;Matrix;Capsid 254;223;230 275;225;232 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. In contrast, R58E, Q59A or Q63A of MA, and E76R or R82E of CA-NTD abrogated the interaction with the C-terminal domain of GAPDH. 2016 Biochemistry and biophysics reports Abstract HIV E76R;Q59A;Q63A;R58E;R82E 43;19;27;13;51 47;23;31;17;55 Matrix;Capsid 35;59 37;61 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Multiple-substituted GAPDH mutant (D256R/K260E/K263E/E267R) retained the oligomeric formation with WT GAPDH in HIV-1 producing cells, but the incorporation level of the hetero-oligomer was decreased in viral particles. 2016 Biochemistry and biophysics reports Abstract HIV D256R;E267R;K260E;K263E 35;53;41;47 40;58;46;52 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. The D256R, K263E or E267R mutation of GAPDH led to the loss of the ability to bind to wild-type (WT) MA, and the D256R/K260E double mutation of GAPDH resulted in the loss of detectable binding activity to WT CA-NTD. 2016 Biochemistry and biophysics reports Abstract HIV D256R;D256R;E267R;K260E;K263E 4;113;20;119;11 9;118;25;124;16 Matrix;Capsid 101;208 103;210 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. These findings indicate that the amino acids Asp256, Lys260, Lys263 and Glu267 of GAPDH is essential for the mechanism of tRNALys3-packaging suppression and the D256R/K260E/K263E/E267R mutant of GAPDH acts in a dominant negative manner to suppress tRNALys3 packaging. 2016 Biochemistry and biophysics reports Abstract HIV D256R;E267R;K260E;K263E 161;179;167;173 166;184;172;178 Asp 45 48 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. Cell culture selections with either EFdA or lamivudine using both subtype B and non-B clinical isolates selected the M184I/V substitutions in reverse transcriptase (RT). 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 117;117 124;124 RT;RT 142;165 163;167 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. CONCLUSIONS: These findings help to alleviate concern that EFdA may not be active against viruses that contain both the M184I/V and E138K substitutions in RT. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;M184I;M184V 132;120;120 137;127;127 RT 155 157 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. In other clinical trials that evaluated rilpivirine together with emtricitabine in first-line therapy, the emergence of both the M184I/V and E138K mutations in RT was demonstrated. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;M184I;M184V 141;129;129 146;136;136 RT 160 162 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. METHODS: Recombinant viruses containing the M184I/V and/or E138K substitutions were generated by site-directed mutagenesis and evaluated in tissue culture for susceptibility to various nucleoside compounds, including EFdA. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;M184I;M184V 59;44;44 64;51;51 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. Moreover, the E138K substitution was not generated in these studies under selection pressure with EFdA. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K 14 19 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. Moreover, the M184I/V and E138K substitutions were shown to be compensatory for each other with regard to both efficiency of RT activity and viral replicative capacity. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;M184I;M184V 26;14;14 31;21;21 RT 125 127 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. OBJECTIVES: We wished to determine whether the E138K mutation in HIV RT together with M184I/V would compromise the activity of EFdA. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;M184I;M184V 47;86;86 52;93;93 RT 69 71 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. RESULTS: Susceptibility to EFdA was retained in M184I/V viruses that also contained the E138K substitution. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;M184I;M184V 88;48;48 93;55;55 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. This creates concern that E138K might emerge as a compensatory mutation for M184I/V in the aftermath of the use of EFdA. 2017 The Journal of antimicrobial chemotherapy Abstract HIV E138K;M184I;M184V 26;76;76 31;83;83 28961903 M184I/V substitutions and E138K/M184I/V double substitutions in HIV reverse transcriptase do not significantly affect the antiviral activity of EFdA. Unlike lamivudine, however, EFdA retained significant activity against viruses containing the M184I/V substitutions. 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 94;94 101;101 28972144 Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. Here, we investigated the mechanism for the evolution of a triple IN substitution (T124N/V165I/T174I) that emerges in cell culture with a representative MINI, KF116. 2017 The Journal of biological chemistry Abstract HIV T124N;T174I;V165I 83;95;89 88;100;94 IN 66 68 28972144 Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. Strikingly, the addition of the third IN substitution (V165I) restored polyprotein processing, virus particle maturation, and significant levels of replication capacity. 2017 The Journal of biological chemistry Abstract HIV V165I 55 60 IN 38 40 28972144 Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. The complex evolutionary pathway for the emergence of resistant viruses, which includes the need for the compensatory V165I IN substitution, highlights a relatively high genetic barrier exerted by MINI KF116. 2017 The Journal of biological chemistry Abstract HIV V165I 118 123 IN 124 126 28972144 Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. Two IN substitutions (T124N/T174I) directly weaken inhibitor binding at the dimer interface of the catalytic core domain but at the same time markedly impair HIV-1 replication capacity. 2017 The Journal of biological chemistry Abstract HIV T124N;T174I 22;28 27;33 IN 4 6 28972144 Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. Unexpectedly, T124N/T174I IN substitutions inhibited proteolytic processing of HIV-1 polyproteins Gag and Gag-Pol, resulting in immature virions. 2017 The Journal of biological chemistry Abstract HIV T124N;T174I 14;20 19;25 GagPol;Gag;IN 106;98;26 113;101;28 28972144 Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. We show that HIV-1 NL4-3(IN T124N/V165I/T174I) confers marked (>2000-fold) resistance to KF116. 2017 The Journal of biological chemistry Abstract HIV T124N;T174I;V165I 28;40;34 33;45;39 IN 25 27 28981637 Rates of virological suppression and drug resistance in adult HIV-1-positive patients attending primary healthcare facilities in KwaZulu-Natal, South Africa. DRMs were detected in 89% of 123 specimens with VF, including M184I/V, K103N/S, K65N/R, V106A/M and Y181C. 2017 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K103S;K65N;K65R;M184I;M184V;V106A;V106M;Y181C 71;71;80;80;62;62;88;88;100 78;78;86;86;69;69;95;95;105 28983848 Prevalence of HIV-1 pre-treatment drug resistance in a southern province of Iran, 2016-2017. Although no major protease inhibitor (PI) resistance mutations were detected, the minor mutations L10F and L33F (2.5% each) as well as several highly frequent polymorphic mutations were identified. 2018 Archives of virology Abstract HIV L10F;L33F 98;107 102;111 PR;PI 18;38 26;40 28983848 Prevalence of HIV-1 pre-treatment drug resistance in a southern province of Iran, 2016-2017. D67G (2.4%), a mutation that reduces susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs) was the only detectable TDR mutation in this population. 2018 Archives of virology Abstract HIV D67G 0 4 NRTI;NRTI 55;100 87;105 28983848 Prevalence of HIV-1 pre-treatment drug resistance in a southern province of Iran, 2016-2017. Two other DRMs, including E138A (9.7%) and V179T (4.9%), which confer resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), were also identified. 2018 Archives of virology Abstract HIV E138A;V179T 26;43 31;48 NNRTI;NNRTI 84;133 120;139 28986714 Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. Among treatment-naive, the detected NRTI and NNRTI resistance mutations were V179T, V75 M and E138A. 2018 Archives of virology Abstract HIV E138A;V179T;V75M 94;77;84 99;82;89 NNRTI;NRTI 45;36 50;40 28986714 Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. Regarding NRTI and NNRTI resistance mutations among treated patients, the most frequent mutation (7%) was M184 V, which causes high level resistance to zidovudin and emtricitabine. 2018 Archives of virology Abstract HIV M184V 106 112 NNRTI;NRTI 19;10 24;14 28986714 Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. V179T causes high level resistance to Efavirenze and Nevirapin. 2018 Archives of virology Abstract HIV V179T 0 5 28986714 Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. V75 M causes intermediate resistance to Stavudine. 2018 Archives of virology Abstract HIV V75M 0 5 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. CONCLUSIONS: The rapid fixation, the lack of detectable immune responses and the significant fitness cost of the K43R mutation suggests that it was strongly selected by host factors other than T cell responses and neutralizing antibodies. 2017 Retrovirology Abstract HIV K43R 113 117 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. However, when fitness costs of both mutations were measured by introducing each mutation into their cognate transmitted/founder (T/F) viral genome, the K43R mutation caused a significant fitness loss while the N323tc mutation had little impact on viral fitness. 2017 Retrovirology Abstract HIV K43R 152 156 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The K43R mutation in the gag gene was first detected at day 91 post screening and was fixed in the viral population at day 273 while the synonymous N323tc mutation was first detected at day 177 and fixed at day 670. 2017 Retrovirology Abstract HIV K43R 4 8 Gag 25 28 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. The analysis of reverse transcriptase showed M184V (68.9%), T215YISF (44.8%), K103N (27.6%) and the analysis results of protease revealed G73SC (13.8%) and I47VA (6.9%). 2017 Iranian journal of public health Abstract HIV G73C;G73S;I47A;I47V;K103N;M184V;T215F;T215I;T215S;T215Y 138;138;156;156;78;45;60;60;60;60 143;143;161;161;83;50;68;68;68;68 RT;PR 16;120 37;128 29029095 Identification of novel bifunctional HIV-1 reverse transcriptase inhibitors. Optimization of compound A led to more potent analogues, which retained similar activities against WT and K103N mutant viruses with submicromolar potency in a cell-based assay. 2018 The Journal of antimicrobial chemotherapy Abstract HIV K103N 106 111 29029095 Identification of novel bifunctional HIV-1 reverse transcriptase inhibitors. RESULTS: Compound A displayed equal or greater potency against many common NNRTI-resistant RTs (K103N and Y181C RTs) relative to WT RT. 2018 The Journal of antimicrobial chemotherapy Abstract HIV K103N;Y181C 96;106 102;111 NNRTI;RT;RT;RT 75;91;112;132 80;94;115;134 29040633 Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014. PDR was defined as >=2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. 2017 The Journal of infectious diseases Abstract HIV G190A;K103N;K65R;M184V;Y181C 105;91;123;112;98 110;96;127;118;103 Pol 80 83 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. The most frequent NNRTIs associated mutations were K103N, V106M and Y188C. 2017 PloS one Abstract HIV K103N;V106M;Y188C 51;58;68 56;63;73 NNRTI 18 24 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. The most frequent NRTIs drug resistance associated mutations are mainly the lamivudine-induced mutation M184V which was detected in 4 patients at T1 and showed a 2 fold increase in the following time points (T2: n = 8) and at (T3: n = 12) and the thymidine analogue mutations (such as D67N, K70R and K219E) which were not-detected at baseline T0 and T1 but were increased progressively to 10 at T2 and to 17 at T3. 2017 PloS one Abstract HIV D67N;K219E;K70R;M184V 285;300;291;104 289;305;295;109 NRTI 18 23 29068286 Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana. The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. 2017 Journal of medical microbiology Abstract HIV K103N;M184V 97;55 102;60 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Accordingly, the two latter mutants are highly resistant to dolutegravir while F190Y shows only moderate or no resistance. 2017 Scientific reports Abstract HIV F190Y 79 84 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Indeed, dolutegravir-binding to wild-type and F190Y integrases are comparable while strongly compromised with G187R and S217K. 2017 Scientific reports Abstract HIV F190Y;G187R;S217K 46;110;120 51;115;125 IN 52 62 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. We also compared dolutegravir-binding to PFV F190Y, G187R and S217K mutants, corresponding to HIV-1 F121Y, G118R and G140S/Q148K mutations that confer low-to-high resistance levels against raltegravir/dolutegravir. 2017 Scientific reports Abstract HIV F190Y;G118R;G140S;G187R;Q148K;S217K 45;107;117;52;123;62 50;112;122;57;128;67 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Overall, 7.3% transmitted and 34.3% acquired DRMs were found, including M184V, thymidine analogue mutations (T215F, D67N, K70R, K219Q), NNRTIs (L100I, Y181C, K103N, V108I, Y188L), and PIs (V82L). 2017 Scientific reports Abstract HIV D67N;K103N;K219Q;K70R;L100I;M184V;T215F;V108I;V82L;Y181C;Y188L 116;158;128;122;144;72;109;165;189;151;172 120;163;133;126;149;77;114;170;193;156;177 NNRTI;PI 136;184 142;187 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Twelve subjects [10 with HIV-1 CRF02_AG, 8 treatment-naive and 4 on 3TC-AZT-NVP] showed 3 to 4 mutations in the Gag P2/NC CS: S373Q/T/A, A374T/S/G/N, T375S/A/N/G, I376V, G381S, and R380K. 2017 Scientific reports Abstract HIV A374G;A374N;A374S;A374T;G381S;I376V;R380K;S373A;S373Q;S373T;T375A;T375G;T375N;T375S 137;137;137;137;170;163;181;126;126;126;150;150;150;150 148;148;148;148;175;168;186;135;135;135;161;161;161;161 Gag;NC 112;119 115;121 29077926 No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir. The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). 2018 The Journal of antimicrobial chemotherapy Abstract HIV G73C;M46I 31;48 35;52 PI 19 21 29077927 Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus. A higher risk of VF was independently associated with baseline viral load >100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with >=1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015). 2018 The Journal of antimicrobial chemotherapy Abstract HIV G140A;G140C;G140S;Q148H;Q148K;Q148N;Q148R 199;199;199;179;179;179;179 208;208;208;190;190;190;190 INSTI 158 163 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Historically, in HIV patients, the K65R mutation and thymidine analogue mutations (TAMs) have been reported to rarely coexist. 2018 AIDS research and human retroviruses Abstract HIV K65R 35 39 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In contrast, in the 87 patients failing TDF, drug resistance mutations at S2 included K65R in 56 (64.4%), TAM-1s in 1 (1.1%), and TAM-2s in 25 patients (28.7%). 2018 AIDS research and human retroviruses Abstract HIV K65R 86 90 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Interestingly, 30.4% of patients with K65R in our study developed TAMs. 2018 AIDS research and human retroviruses Abstract HIV K65R 38 42 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. These were exclusively K219E +- D67N and were not predicted to confer a resistance cost to future AZT-containing regimens. 2018 AIDS research and human retroviruses Abstract HIV D67N;K219E 32;23 36;28 29091218 HIV-1 DNA ultra-deep sequencing analysis at initiation of the dual therapy dolutegravir + lamivudine in the maintenance DOLULAM pilot study. At the time of DOLULAM initiation, M184V was observed in DNA NGS in five patients, including one as MRV. 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184V 35 40 29091218 HIV-1 DNA ultra-deep sequencing analysis at initiation of the dual therapy dolutegravir + lamivudine in the maintenance DOLULAM pilot study. Combining all available genotype data, an M184I/V was observed in 17 of 27 (63%) of the patients. 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 42;42 49;49 29091218 HIV-1 DNA ultra-deep sequencing analysis at initiation of the dual therapy dolutegravir + lamivudine in the maintenance DOLULAM pilot study. Conclusions: These first NGS data on HIV DNA at initiation of a switch study showed (i) a high proportion of patients harbouring defective viral genomes, whose mutation M184I is a marker, and (ii) a low number of patients in whom M184V remained as a major viral variant in PBMCs. 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 169;230 174;235 29091218 HIV-1 DNA ultra-deep sequencing analysis at initiation of the dual therapy dolutegravir + lamivudine in the maintenance DOLULAM pilot study. Most M184V were detected in historical RNA genotypes (n = 8 of 11), whereas M184I were exclusively detected in DNA genotypes (n = 10, including 7 as MRV). 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 76;5 81;10 29091218 HIV-1 DNA ultra-deep sequencing analysis at initiation of the dual therapy dolutegravir + lamivudine in the maintenance DOLULAM pilot study. Objectives: A virological substudy was conducted to assess the prevalence of M184I/V mutations at dual therapy initiation using historical DNA/RNA genotypes and baseline DNA genotype obtained by next-generation sequencing (NGS). 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 77;77 84;84 29091218 HIV-1 DNA ultra-deep sequencing analysis at initiation of the dual therapy dolutegravir + lamivudine in the maintenance DOLULAM pilot study. Ten patients displayed defective viral genomes in cellular reservoirs, all including M184I and stop codons. 2017 The Journal of antimicrobial chemotherapy Abstract HIV M184I 85 90 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation. 2017 Viruses Abstract HIV E529D 53 58 NRTI 63 67 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. 2017 Viruses Abstract HIV A435L;A508S;E529D;E529D;L484I;L517I;Q509L;Q524E;S468A;T470S 14;42;73;213;35;56;49;63;21;28 19;47;78;218;40;61;54;68;26;33 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. As a result, L33F appears to act as a molecular anchor, reducing the flexibility of the 30s loop (residues 29-35) and the 80s loop (residues 79-84). 2015 Biochemistry and biophysics reports Abstract HIV L33F 13 17 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. In contrast to other PR L33F DRV complexes, the structure of MDR769 L33F complexed with DRV reported here displays the protease flaps in an open conformation. 2015 Biochemistry and biophysics reports Abstract HIV L33F 24 28 PR;PR 119;21 127;23 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The L33F mutation increases noncovalent interactions in the hydrophobic pocket of the PR compared to the wild-type (WT) structure. 2015 Biochemistry and biophysics reports Abstract HIV L33F 4 8 PR 86 88 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. To identify the structural mechanisms associated with the DRV resistance mutation L33F, we performed X-ray crystallographic studies with a multi-drug resistant HIV-1 protease isolate that contains the L33F mutation (MDR769 L33F). 2015 Biochemistry and biophysics reports Abstract HIV L33F;L33F 82;201 86;205 PR 166 174 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Absence of K65R supports the use of tenofovir-containing regimens as preferred first-line and as suitable drug for second-line combinations, in this setting with significant HIV-1 genetic diversity. 2017 BMC research notes Abstract HIV K65R 11 15 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Overall, 32% (37/116) patients presented >= one major drug resistant mutation(s), with 29% (34/116) to nucleos(t)ide reverse transcriptase inhibitors (67% [29/43] M184V/I, 30% [13/43] T215Y/F, 19% [8/43] V75A/F/I/L/M, 9% [4/43] K70P/R/W, 9% [4/43] K219E/N/Q and 5% [2/43] A62V); 86% (37/43) to non-nulceos(t)ide reverse transcriptase inhibitors (30% [13/43] K103N/S/E, 26% [11/43] Y181C/V/F/L, 2% [1/43] L100I, 2% [1/43] F227L, 2% [1/43] P225H); and 2% (1/43) to protease inhibitors (M46I, I54V, V82S). 2017 BMC research notes Abstract HIV A62V;F227L;I54V;K103E;K103N;K103S;K219E;K219N;K219Q;K70P;K70R;K70W;L100I;M184I;M184V;M46I;P225H;T215F;T215Y;V75A;V75F;V75I;V75L;V75M;V82S;Y181C;Y181F;Y181L;Y181V 272;421;490;358;358;358;248;248;248;228;228;228;404;163;163;484;438;184;184;204;204;204;204;204;496;381;381;381;381 276;426;494;367;367;367;257;257;257;236;236;236;409;170;170;488;443;191;191;216;216;216;216;216;500;392;392;392;392 NRTI;RT;PR 103;312;463 138;333;471 29128646 HIV drug resistance following a decade of the free antiretroviral therapy programme in India: A review. The temporal trend analysis of individual DRM from sequences retrieved during 2004-2014 indicated a rising trend in K65R mutations (p=0.013). 2018 International journal of infectious diseases Abstract HIV K65R 116 120 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. 2017 BMC infectious diseases Abstract HIV M28T;Q30H;Q30R;Y93H 77;87;87;117 83;93;93;121 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. RESULTS: The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). 2017 BMC infectious diseases Abstract HIV A30K;L31F;L31V;M28V;Q30H;Q30R;Y93H;Y93H 167;128;128;93;103;103;139;176 172;135;135;99;109;109;143;180 29136743 [Drug resistance mutations and its associated factors among 579 HIV/AIDS patients experiencing failure of antiretroviral therapy in Jiangsu Province, China]. M184V/I and K103N/Q were the highest frequency of NRTI and NNRTI resistance mutation, the prevalence of M184V/I and K103N/Q were 28.15% and 22.28%, respectively. 2017 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV K103N;K103N;K103Q;K103Q;M184I;M184I;M184V;M184V 12;116;12;116;0;104;0;104 19;123;19;123;7;111;7;111 NNRTI;NRTI 59;50 64;54 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. For all E138A LTNs, the Re was >1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was >1 between 2006 and 2011 and approximately equal to 1 thereafter. 2017 Genes Abstract HIV E138A;E138A 8;85 13;90 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. For the K103N LTN, the Re was >1 between 2008 and the first half of 2013. 2017 Genes Abstract HIV K103N 8 13 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. 2017 Genes Abstract HIV E138A;K103N 10;0 15;5 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. 2017 Genes Abstract HIV E138A;K103N 64;74 70;79 NNRTI 36 41 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. Among these, the frequencies of L101I, T122I, and V201I increased over time, whereas the frequency of M154I decreased. 2017 Virology journal Abstract HIV L101I;M154I;T122I;V201I 32;102;39;50 37;107;44;55 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. Moreover, L101I, T122I, T124A, T125A, M154I, and V201I covaried with non-resistance-associated variants. 2017 Virology journal Abstract HIV L101I;M154I;T122I;T124A;T125A;V201I 10;38;17;24;31;49 15;43;22;29;36;54 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. Some minor INSTI resistance mutations (T124A, V151I, K156 N, T206S, S230 N) and some INSTI-selected mutations (M50I, L101I, T122I, T124 N, T125A, M154I, G193E, V201I) were identified at overall frequencies >5%. 2017 Virology journal Abstract HIV G193E;K156N;L101I;M154I;M50I;S230N;T122I;T124A;T124N;T125A;T206S;V151I;V201I 153;53;117;146;111;68;124;39;131;139;61;46;160 158;59;122;151;115;74;129;44;137;144;66;51;165 INSTI;INSTI 11;85 16;90 29140932 Characteristics of Treatment-experienced HIV-infected African Children and Adolescents Initiating Darunavir and/or Etravirine-based Antiretroviral Treatment. Forty seven patients (98.9%) had HIV genotype results: 41 (87.2%) had >=1 nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistance mutation (RM), predominantly M184V (76.6%; n = 36); 31 (65.9%) had >=1 non-NRTI-RM, including 27 (57.4%) with >=1 ETR-RM; 30 (63.8%) had >=3 protease inhibitor RM, including 20 (42.6%) with >=1 DRV-RM. 2018 The Pediatric infectious disease journal Abstract HIV M184V 167 172 NRTI;NNRTI;PR;NRTI 74;209;279;121 109;217;287;125 29143565 HIV-1 resistance rarely observed in patients using darunavir once-daily regimens across clinical studies. Among 1103 subjects using a nucleos(t)ide reverse transcriptase inhibitor (N[t]RTI) backbone, 10 (0.9%) developed >= 1 N(t)RTI RAM (8 had the emtricitabine RAM M184I/V). 2017 HIV clinical trials Abstract HIV M184I;M184V 160;160 167;167 NRTI;NRTI;NRTI 28;75;119 63;82;126 29152052 Discovery of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the Tolerant Region I of NNIBP. Notably, both compounds showed potent antiviral activity against K103N (EC50 = 0.032 and 0.070 muM) and E138K (EC50 = 0.035 and 0.045 muM, respectively). 2017 ACS medicinal chemistry letters Abstract HIV E138K;K103N 104;65 109;70 29156381 Structure-based methods to predict mutational resistance to diarylpyrimidine non-nucleoside reverse transcriptase inhibitors. Consistent with previous studies, mutation K101P is predicted to confer high-level resistance to DAPYs. 2018 Journal of molecular graphics & modelling Abstract HIV K101P 43 48 29156603 Adding an Artificial Tail-Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile. HP23, the shortest CHR peptide, exhibits better anti-HIV-1 activity than T20, but the HIV-1 strains with E49K mutations in gp41 will become resistant to it. 2017 Molecules (Basel, Switzerland) Abstract HIV E49K 105 109 gp41 123 127 29165086 Association Between LTF Polymorphism and Risk of HIV-1 Transmission Among Zambian Seropositive Mothers. METHODS: LTF T29A and R47K polymorphisms were genotyped, using allelic specific fluorescent probes and real time PCR, in a population comprising 101 HIV-1 positive mothers and 333 children born to seropositive mothers. 2018 Current HIV research Abstract HIV R47K;T29A 22;13 26;17 29165086 Association Between LTF Polymorphism and Risk of HIV-1 Transmission Among Zambian Seropositive Mothers. OBJECTIVES: LTF T29A and R47K genetic variants were analysed in a Zambian population to unravel if these polymorphisms could play a role in HIV-1 mother-to-child HIV-1 transmission. 2018 Current HIV research Abstract HIV R47K;T29A 25;16 29;20 29165086 Association Between LTF Polymorphism and Risk of HIV-1 Transmission Among Zambian Seropositive Mothers. RESULTS: Maternal LTF T29A A/A and A/G genotypes were found to be associated with decreased risk of HIV-1 MTCT, being more frequent among non-transmitter mothers respect to transmitter mothers. 2018 Current HIV research Abstract HIV T29A 22 26 29165086 Association Between LTF Polymorphism and Risk of HIV-1 Transmission Among Zambian Seropositive Mothers. Two polymorphisms, T29A and R47K, in the exon 1 region of the LTF gene (encoding for the lactoferrin protein) were previously described as able to influence the lactoferrin antimicrobial function. 2018 Current HIV research Abstract HIV R47K;T29A 28;19 32;23 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Moreover, the maturation-arresting SP1 mutation T8I also induces helical structure in SP1 and further global dynamical and conformational changes in CA. 2017 Nature communications Abstract HIV T8I 48 51 SP1;SP1;Capsid 35;86;149 38;89;151 29212041 Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains. We used a 96-well expression-screening format to assess the ability of artificial disulfides and Ile559Pro substitution (DS-SOSIP) to produce soluble cleaved-Env trimers; from 180 Env strains, 20 yielded prefusion closed trimers. 2017 Cell reports Abstract HIV I559P 97 106 Env;Env 158;180 161;183 29212076 Resistance-Associated Mutations and Polymorphisms among Integrase Inhibitor-Naive HIV-1 Patients in Kuwait. However, the accessory mutation E157Q was found in 1 patient with CRF02_AG, and the polymorphic mutations L74M/I that may contribute to a reduced susceptibility to INSTIs in the presence of major mutations were observed in 6 (13.3%) patients with non-B subtypes and 1 (12.5%) patient with the B subtype. 2017 Intervirology Abstract HIV E157Q;L74I;L74M 32;106;106 37;112;112 INSTI 164 170 29212937 Experimental Adaptive Evolution of Simian Immunodeficiency Virus SIVcpz to Pandemic Human Immunodeficiency Virus Type 1 by Using a Humanized Mouse Model. Moreover, viral RNA sequencing of MB897-infected humanized mice identified a nonsynonymous mutation in env, a G413R substitution in gp120. 2018 Journal of virology Abstract HIV G413R 110 115 gp120;Env 132;103 137;106 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Together, these modifications further stabilized the resulting SOSIP.v5.2 S306L/R308L trimers in the prefusion state in which V3 is sequestered. 2018 The Journal of biological chemistry Abstract HIV R308L 80 85 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. V3 immunogenicity can be diminished, but not abolished, by reducing the conformational flexibility of trimers via targeted sequence changes, including an A316W substitution in V3, that create the SOSIP.v4.1 and SOSIP.v5.2 variants. 2018 The Journal of biological chemistry Abstract HIV A316W 154 159 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. Finally, a lateral flow enzyme-linked immunosorbent assay (ELISA) differentiates between OLA-labeled products with or without M184V. 2018 Analytical biochemistry Abstract HIV M184V 126 131 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. The first step isothermally amplifies a section of HIV-1 reverse transcriptase containing M184V using a recombinase polymerase amplification (RPA) assay. 2018 Analytical biochemistry Abstract HIV M184V 90 95 RT;Pol 57;116 78;126 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. This work presents a proof-of-concept assay to detect M184V, the most common drug resistance mutation after first-line antiretroviral therapy failure, in a paper format. 2018 Analytical biochemistry Abstract HIV M184V 54 59 29237828 Identification of Novel Structural Determinants in MW965 Env That Regulate the Neutralization Phenotype and Conformational Masking Potential of Primary HIV-1 Isolates. Substituting the sensitizing mutations Y384C and K502N at these positions into several resistant primary Envs resulted in conversion to neutralization-sensitive phenotypes, demonstrating the generalizability of this effect. 2018 Journal of virology Abstract HIV K502N;Y384C 49;39 54;44 Env 105 109 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Any impact of the high prevalence of major accessory mutations, especially E157Q, requires long-term follow-up studies. 2018 AIDS (London, England) Abstract HIV E157Q 75 80 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. One patient had a primary DRMs (0.3%, 1/270), but 17 (6.3%) had one major accessory DRM, of which 12 were E157Q. 2018 AIDS (London, England) Abstract HIV E157Q 106 111 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. The K103N mutation was detected most commonly in 68.9% (31/45) individuals with HIVDR mutations, with 20/26 (76.9%) of treatment naive FSW with detectable resistance having this mutation. 2017 PloS one Abstract HIV K103N 4 9 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. The M184V mutation was found in both FSWs on treatment (12/14, 85.7%) and those defaulting (1/5, 20.0%). 2017 PloS one Abstract HIV M184V 4 9 29253097 ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL. Three participants with VF, had undetected plasma dolutegravir at >=1 time points; the M184V and R263R/K mutations developed in 1 participant. 2018 Clinical infectious diseases Abstract HIV M184V;R263K;R263R 87;97;97 92;104;104 29262955 Lamivudine monotherapy in children and adolescents: The devil is in the detail. Lamivudine monotherapy is a common choice when holding regimens are used, on the premise that the lamivudine-associated M184V resistance mutation reduces viral replication and may maintain clinical and immunological stability compared with discontinuing treatment altogether. 2017 South African medical journal Abstract HIV M184V 120 125 29264355 Observed HIV drug resistance associated mutations amongst naive immunocompetent children in Yaounde, Cameroon. The observed mutations for NRTI were K65R, T215I and K219E (33.0% each) and for NNRTI: V106M, Y181C and Y188H (6.0% each). 2017 Germs Abstract HIV K219E;K65R;T215I;V106M;Y181C;Y188H 53;37;43;87;94;104 58;41;48;92;99;109 NNRTI;NRTI 80;27 85;31 29275329 Amino acid residues in HIV-2 reverse transcriptase that restrict the development of nucleoside analogue resistance through the excision pathway. Here, we demonstrate that mutant M41L/D67N/K70R/S215Y HIV-2 RT lacks ATP-dependent excision activity, and recombinant virus containing this RT remains susceptible to AZT inhibition. 2018 The Journal of biological chemistry Abstract HIV D67N;K70R;M41L;S215Y 38;43;33;48 42;47;37;53 RT;RT 60;140 62;142 29275329 Amino acid residues in HIV-2 reverse transcriptase that restrict the development of nucleoside analogue resistance through the excision pathway. Interestingly, recombinant HIV-2 carrying a mutant D67N/K70R/M73K RT showed 10-fold decreased AZT susceptibility and increased rescue efficiency on AZT- or tenofovir-terminated primers, as compared with the double-mutant D67N/K70R. 2018 The Journal of biological chemistry Abstract HIV D67N;K70R;M73K;D67N;K70R 51;56;61;221;226 55;60;65;225;230 RT 66 68 29275329 Amino acid residues in HIV-2 reverse transcriptase that restrict the development of nucleoside analogue resistance through the excision pathway. Mutations of the excision pathway such as M41L, D67N, K70R, or S215Y (known as thymidine-analogue resistance mutations (TAMs)) are rare in the virus from HIV-2-infected individuals. 2018 The Journal of biological chemistry Abstract HIV D67N;K70R;M41L;S215Y 48;54;42;63 52;58;46;68 29291935 Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains. Among them, the most promising N1-aryl-2-arylthioacetamido-benzimidazoles and N1-aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K. 2018 Bioorganic & medicinal chemistry Abstract HIV E138K;K103N;L100I;Y181C;Y188L 316;292;285;299;306 321;297;290;304;311 NNRTI 219 225 29291935 Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains. The best results were observed for derivatives 29 and 33 active also against the double mutants F227L and V106A. 2018 Bioorganic & medicinal chemistry Abstract HIV F227L;V106A 96;106 101;111 29294588 [Analysis on HIV-1 subtypes and transmission clusters in newly reported HIV/AIDS cases in Yiwu, Zhejiang Province, 2016]. Seven cases with surveillance drug resistant mutations (SDRM) were found, including 5 cases of M46L (3.3%), and one case of F77L or Y181C. 2017 Zhonghua liu xing bing xue za zhi Abstract HIV F77L;M46L;Y181C 124;95;132 128;99;137 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. In this study, we carried out a detailed investigation of this question by using tetherin variants in which one or both sites of N-linked glycosylation were mutated (N65A, N92A, and N65,92A), and chemical inhibitors that prevent glycosylation at specific stages of oligosaccharide were added or modified. 2018 Viruses Abstract HIV N65A;N92A 166;172 170;176 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. The single N-linked glycosylation mutants, N65A and N92A, efficiently inhibited the release of Vpu-defective human immunodeficiency virus type 1 (HIV-1). 2018 Viruses Abstract HIV N65A;N92A 43;52 47;56 Vpu 95 98 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. BACKGROUND: Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. 2018 Retrovirology Abstract HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 230;217;217;217;208;208 235;226;226;226;215;215 IN 44 53 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Half the cases had the G190A resistance mutation. 2018 PloS one Abstract HIV G190A 23 28 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. 2018 PloS one Abstract HIV G190A 86 91 NNRTI 39 75 29321334 Mechanism of HIV-1 Resistance to an Electronically Constrained alpha-Helical Peptide Membrane Fusion Inhibitor. Three mutant viruses, which possessed two (N43K/E49A) or three (Q39R/N43K/N126K and N43K/E49A/N126K) amino acid substitutions in the N- and C-terminal repeat regions of gp41 were identified as conferring high resistance to SC29EK and cross-resistance to the first-generation (T20 and C34) and newly designed (sifuvirtide, MT-SC29EK, and 2P23) fusion inhibitors. 2018 Journal of virology Abstract HIV Q39R;E49A;N126K;N126K;N43K;N43K;N43K;E49A 64;89;74;94;69;84;43;48 68;93;79;99;73;88;47;52 gp41 169 173 29325134 Continued propagation of the CRF19_cpx variant among HIV-positive MSM patients in Spain. Conclusions: We demonstrate that this variant has spread in Spain in recent years among young HIV-positive MSM and we note a recent expansion in southern Spain in patients who carry mutation G190A. 2018 The Journal of antimicrobial chemotherapy Abstract HIV G190A 191 196 29325134 Continued propagation of the CRF19_cpx variant among HIV-positive MSM patients in Spain. We found a larger cluster that grouped nine patients from southern Spain (Malaga and Seville), of which six presented mutation G190A. 2018 The Journal of antimicrobial chemotherapy Abstract HIV G190A 127 132 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. An adapted version of the assay was used to obtain error rates of RNA-dependent DNA synthesis for several RTs, including wild-type HIV-1BH10, HIV-1ESP49, AMV and MLV RTs, and the high-fidelity mutants of HIV-1ESP49 RT K65R and K65R/V75I. 2018 Scientific reports Abstract HIV K65R;K65R;V75I 218;227;232 222;231;236 RT;RT;RT 106;166;215 109;169;217 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Analysis of the RNA-dependent mutational spectra revealed a higher tendency to introduce large deletions at the initiation of reverse transcription by all HIV-1 RTs except the double-mutant K65R/V75I. 2018 Scientific reports Abstract HIV K65R;V75I 190;195 194;199 RT;RT 126;161 147;164 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. A H69D mutation in PR abolished autoprocessing of SigP-containing fusion precursors whereas it only partially suppressed autoprocessing of fusion precursors lacking SigP. 2018 PloS one Abstract HIV H69D 2 6 PR 19 21 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. On the contrary, Q65R mutant of Vpr, which lacks ubiquitination activity, was deficient in both chromatin remodelling and RPA70 loading on to the chromatin. 2018 Retrovirology Abstract HIV Q65R 17 21 Vpr 32 35 29342281 Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen. Conclusions: Assessment of virological response in 39 patients initiating an INI-based regimen with E157Q-mutated virus, in combination with phenotypic analysis, suggests that particular attention should be paid to antiretroviral-naive patients and dolutegravir should be preferentially used in these patients. 2018 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 100 105 IN 77 80 29342281 Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay. 2018 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 0 5 29342281 Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen. Objectives: To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen. 2018 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;E157Q 59;156 64;161 IN;IN;IN;IN 87;204;98;190 96;207;100;192 29342281 Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen. Results: Prevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. 2018 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 27 32 IN;IN 84;66 87;68 29342281 Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. 2018 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 36 41 IN;IN 12;69 15;72 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Further in vitro studies on R263K mutants showed a moderate increase in phenotypic resistance level and a drastic reduction in viral replicative capacity. 2018 Viruses Abstract HIV R263K 28 33 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The aim of this manuscript was to review main in vivo and in vitro knowledge about two particular integrase resistance-associated mutations: R263K and E157Q. 2018 Viruses Abstract HIV E157Q;R263K 151;141 156;146 IN 98 107 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The E157Q mutation is polymorphic, found between 1.7% and 5.6% of viral sequences issued from ART-naive patients depending on the viral subtype; as well as acquired resistance emerging at failure of a raltegravir-based regimen in two case reports. 2018 Viruses Abstract HIV E157Q 4 9 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The R263K mutation was the first mutation rarely found selected at time of virological failure in patients failing a first-line dolutegravir-based treatment. 2018 Viruses Abstract HIV R263K 4 9 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. We reported data on phenotypic resistance level of E157Q mutants and virological response of patients harboring a E157Q virus initiating an INI-based regimen, showing that dolutegravir might be the most recommended INI in such patients. 2018 Viruses Abstract HIV E157Q;E157Q 51;114 56;119 IN;IN 140;215 143;218 29349445 Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored "hydrophobic channel". Against mutant strains Y181C, Y188L and F227L + V106A, Z17 showed double-digit nanomolar inhibitory activity with EC50 values 27 nM, 98 nM and 30 nM, respectively. 2018 Organic & biomolecular chemistry Abstract HIV F227L;V106A;Y181C;Y188L 40;48;23;30 45;53;28;35 29349445 Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored "hydrophobic channel". Notably, Z13 also showed the most potent activity against HIV-1 mutant strains including K103N (EC50 = 10 nM), E138K (EC50 = 22 nM) and RES056 (EC50 = 0.935 muM). 2018 Organic & biomolecular chemistry Abstract HIV E138K;K103N 111;89 116;94 29353724 Discovery of biphenyl-substituted diarylpyrimidines as non-nucleoside reverse transcriptase inhibitors with high potency against wild-type and mutant HIV-1. Compound 4b displayed an EC50 value of 1 nM against HIV-1 IIIB, 1.3 nM against L100I, 0.84 nM against K103 N, 1.5 nM against Y181C, 11 nM against Y188L, 2 nM against E138K, 10 nM against K103 N + Y181C, and almost 110 nM against F227L + V106. 2018 European journal of medicinal chemistry Abstract HIV E138K;F227L;K103N;K103N;L100I;Y181C;Y181C;Y188L 166;229;102;187;79;125;196;146 171;234;108;193;84;130;201;151 29369826 Increase in transmitted drug resistance in migrants from sub-Saharan Africa diagnosed with HIV-1 in Sweden. An MSM transmission cluster dating back to the 1990s with the M41L SDRM was identified. 2018 AIDS (London, England) Abstract HIV M41L 62 66 29373677 Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance. Failure of dolutegravir treatment was observed concomitant with the appearance of N155H-K211R-E212T mutations in the integrase (IN) gene in addition to the polymorphic K156N mutation that was present at baseline in this patient. 2018 The Journal of antimicrobial chemotherapy Abstract HIV E212T;K156N;K211R;N155H 94;168;88;82 99;173;93;87 IN;IN 117;128 126;130 29373677 Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance. Interestingly, the association of only N155H and K156N is sufficient for significant resistance to dolutegravir. 2018 The Journal of antimicrobial chemotherapy Abstract HIV K156N;N155H 49;39 54;44 29373677 Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance. Methods: The impact of N155H-K156N-K211R-E212T mutations was studied in cell-free, culture-based assays and by molecular modelling. 2018 The Journal of antimicrobial chemotherapy Abstract HIV E212T;K156N;K211R;N155H 41;29;35;23 46;34;40;28 29373677 Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance. Results: Cell-free and culture-based assays confirm that selected mutations in the patient, in the context of the polymorphic mutation K156N present at the baseline, lead to high resistance to dolutegravir requiring that the analysis be done at timepoints longer than usual to properly reveal the results. 2018 The Journal of antimicrobial chemotherapy Abstract HIV K156N 135 140 29373677 Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance. This study confirms that a pathway including N155H can be selected in patients treated with dolutegravir with the help of the polymorphic K156N that acts as a secondary mutation that enhances the resistance to dolutegravir. 2018 The Journal of antimicrobial chemotherapy Abstract HIV K156N;N155H 138;45 143;50 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Here, we demonstrate that a Q151M substitution alone at the nucleotide-binding site (N-site) of human immunodeficiency virus type-1 (HIV-1) RT renders HIV-1 highly sensitive to entecavir (ETV), a potent nucleoside analogue RT inhibitor (NRTI) against HBV. 2018 Scientific reports Abstract HIV Q151M 28 33 NRTI;RT;RT 237;140;223 241;142;225 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We thus solved the crystal structures of HIV-1 RTQ151M:DNA complex with bound dGTP or ETV-triphosphate (ETV-TP). 2018 Scientific reports Abstract HIV Q151M 49 54 RT 47 49 29397520 An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L upward arrowN upward arrowL PR mutant. A mutation and insertion designated L38L N L PR was recently reported from subtype of C-SA HIV-1. 2018 Journal of computer-aided molecular design Abstract HIV L38L 36 40 PR 45 47 29397520 An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L upward arrowN upward arrowL PR mutant. AIM analysis showed that the interaction between the QM region of the L38L N L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. 2018 Journal of computer-aided molecular design Abstract HIV L38L 70 74 PR 79 81 29397520 An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L upward arrowN upward arrowL PR mutant. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L N L PR enzyme and FDA approved drugs. 2018 Journal of computer-aided molecular design Abstract HIV L38L 116 120 PR 125 127 29397520 An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L upward arrowN upward arrowL PR mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L N L PR in comparison with subtype C-SA HIV-1 PR. 2018 Journal of computer-aided molecular design Abstract HIV L38L 115 119 PR;PR 124;165 126;167 29410019 Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. During passage with Q148H virus, G140S arose by day 14, followed by G149A and C56S. 2018 Antiviral research Abstract HIV C56S;G140S;G149A;Q148H 78;33;68;20 82;38;73;25 29410019 Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. Signature mutant viruses G140S/Q148H in which C56S and G149A were added acquired further INSTI resistance in conjunction with diminished integration activity, which yielded slower growth under drug-free conditions. 2018 Antiviral research Abstract HIV C56S;G140S;G149A;Q148H 46;25;55;31 50;30;60;36 INSTI 89 94 29410019 Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. Using site-directed mutagenesis, we obtained HIV molecular clones containing mutations encoding C56S and G149A in the integrase-coding region. 2018 Antiviral research Abstract HIV C56S;G149A 96;105 100;110 IN 118 127 29415189 Minority resistant variants are also present in HIV-2-infected antiretroviral-naive patients. The most prevalent MRV was the PI RAM I50V detected in three samples. 2018 The Journal of antimicrobial chemotherapy Abstract HIV I50V 38 42 PI 31 33 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. NGS revealed previously unidentified minority variant protease mutations (G73D, I54T, L89V) in three samples, at frequencies ranging between 2% and 10%. 2018 Journal of clinical virology Abstract HIV G73D;I54T;L89V 74;80;86 78;84;90 PR 54 62 29461980 Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. 2018 The Journal of clinical investigation Abstract HIV I47V 24 28 29461980 Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. 2018 The Journal of clinical investigation Abstract HIV I47V;I47V 203;153 207;201 HIV infections 49 63 29462322 Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa. Accessory mutations occurred at a prevalence of 15.1% at the >=20% threshold (23.1% in subtype A, 8.7% C, 11.6% D, 25% G and 23.8% in recombinants), and included L74I/M (10.4%), Q95K (0.5%), T97A (4%), E157Q (0.7%) and G163R/K (0.7%). 2018 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;G163K;G163R;L74I;L74M;Q95K;T97A 202;219;219;162;162;178;191 207;226;226;168;168;182;195 29462322 Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa. Major INSTI resistance mutations were detected only at <20% threshold, at a prevalence of 2.4% (2.5% in subtype A, 2.4% C, 0% D, 8.3% G and 2.4% in recombinants) and included T66A/I (0.7%), E92G (0.5%), Y143C/S (0.7%), S147G (0.2%) and Q148R (0.5%). 2018 The Journal of antimicrobial chemotherapy Abstract HIV E92G;Q148R;S147G;T66A;T66I;Y143C;Y143S 190;236;219;175;175;203;203 194;241;224;181;181;210;210 INSTI 6 11 29496992 Distinct functions for the membrane-proximal ectodomain region (MPER) of HIV-1 gp41 in cell-free and cell-cell viral transmission and cell-cell fusion. Domain swapping indicated that the disparate W666A phenotypes of the cell-free transmitted/founder viruses are controlled by sequences in variable regions 1, 2, and 4 of gp120. 2018 The Journal of biological chemistry Abstract HIV W666A 45 50 gp120 170 175 29496992 Distinct functions for the membrane-proximal ectodomain region (MPER) of HIV-1 gp41 in cell-free and cell-cell viral transmission and cell-cell fusion. The sequential passaging of an MPER mutant (W672A) in peripheral blood mononuclear cells enabled selection of viral revertants with loss-of-glycan suppressor mutations in variable region 1, suggesting a functional interaction between variable region 1 and the MPER. 2018 The Journal of biological chemistry Abstract HIV W672A 44 49 29496992 Distinct functions for the membrane-proximal ectodomain region (MPER) of HIV-1 gp41 in cell-free and cell-cell viral transmission and cell-cell fusion. We observed contrasting effects on cell-free virus infectivity when W666A was introduced to two transmitted/founder isolates, but both mutants could still mediate cell-cell spread. 2018 The Journal of biological chemistry Abstract HIV W666A 68 73 29496992 Distinct functions for the membrane-proximal ectodomain region (MPER) of HIV-1 gp41 in cell-free and cell-cell viral transmission and cell-cell fusion. Whereas cell-free viruses bearing W666A and I675A substitutions in the MPER lacked infectivity, cell-associated mutant viruses were able to initiate robust spreading infection. 2018 The Journal of biological chemistry Abstract HIV I675A;W666A 44;34 49;39 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Compared to rHIVWT, rHIVV32I was highly susceptible to DRV and had significantly reduced fitness, explaining why V32I did not emerge upon selection of rHIVWT with DRV. 2018 mBio Abstract HIV V32I 113 117 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Here, we show that the preexistence of certain single amino acid substitutions such as V32I, I54M, A71V, and I84V in HIV-1 protease facilitates the development of high-level DRV resistance. 2018 mBio Abstract HIV A71V;I54M;I84V;V32I 99;93;109;87 103;97;113;91 PR 123 131 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. However, wild-type HIVNL4-3 (rHIVWT) failed to acquire V32I and did not develop DRV resistance. 2018 mBio Abstract HIV V32I 55 59 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Interestingly, all in vitro-selected highly DRV-resistant HIV-1 variants acquired V32I but never emerged in wild-type HIV (HIVWT), and V32I itself rendered HIV-1 more sensitive to DRV and reduced viral fitness compared to HIVWT, strongly suggesting that the emergence of V32I plays a critical role in the development of HIV-1's resistance to DRV. 2018 mBio Abstract HIV V32I;V32I;V32I 82;135;271 86;139;275 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The results also show that attention should be paid to the initiation or continuation of DRV-containing regimens in people with HIV-1 containing the V32I substitution.IMPORTANCE Darunavir (DRV) is the only protease inhibitor (PI) recommended as a first-line therapeutic and represents the most widely used PI for treating HIV-1-infected individuals. 2018 mBio Abstract HIV V32I 149 153 PR;PI;PI 206;226;306 214;228;308 HIV infections 322 336 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These results suggest that V32I is a critical amino acid substitution in multiple pathways toward HIV-1's DRV resistance development and elucidate, at least in part, a mechanism of DRV's high genetic barrier to development of drug resistance. 2018 mBio Abstract HIV V32I 27 31 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We also reported that four amino acid substitutions (V32I, L33F, I54M, and I84V) identified in the protease of HIVDRVRP51 are largely responsible for its high-level resistance to DRV. 2018 mBio Abstract HIV I54M;I84V;L33F;V32I 65;75;59;53 69;79;63;57 PR 99 107 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We found that V32I is a key substitution, which rarely occurs, but once it occurs, it predisposes HIV-1 to develop high-level DRV resistance. 2018 mBio Abstract HIV V32I 14 18 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. When two infectious recombinant HIV-1 clones carrying I54M and I84V (rHIVI54M and rHIVI84V, respectively) were selected in the presence of DRV, V32I emerged, and the virus rapidly developed high-level DRV resistance. 2018 mBio Abstract HIV I54M;I84V;V32I 54;63;144 58;67;148 29534929 First discovery of a potential carbonate prodrug of NNRTI drug candidate RDEA427 with submicromolar inhibitory activity against HIV-1 K103N/Y181C double mutant strain. Compound 6 was found to inhibit the wild-type (WT) and K103N/Y181C double mutant HIV-1 strains at nano- and submicromolar concentrations, respectively. 2018 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 55;61 60;66 29546333 Recent and Rapid Transmission of HIV Among People Who Inject Drugs in Scotland Revealed Through Phylogenetic Analysis. Results: All 104 outbreak sequences originated from Scotland and contained E138A and V179E. 2018 The Journal of infectious diseases Abstract HIV E138A;V179E 75;85 80;90 29550516 Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan. In addition, the improvement of the EEV formation via the A34R gene mutation may also be potent in other poxvirus vector-based vaccines against HIV-1 or other pathogens and even cancer in the future. 2018 Antiviral research Abstract HIV A34R 58 62 29550516 Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan. Meanwhile, the application of the A34R mutation on another VV-based HIV-1 vaccine candidate, VTKgpe, also exhibited a similar immune enhancement effect with no enhanced virulence. 2018 Antiviral research Abstract HIV A34R 34 38 29550516 Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan. The results in this study suggested that rVTT-A34Rmut is a potentially improved vaccine vector candidate for human application. 2018 Antiviral research Abstract HIV A34R 46 50 29550516 Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan. The results were consistent with our hypothesis: the A34R mutant-based HIV-1 vaccine candidate rVTT-A34Rmut-Env produced more HIV-1 Env antigen in vitro and in vivo, and thus led to an improved HIV-1 Env-specific T cell immune response, binding antibody, and even the neutralizing antibody response in mice without increased virulence. 2018 Antiviral research Abstract HIV A34R 53 57 Env;Env;Env 108;132;200 111;135;203 29550516 Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan. To this end, an A34R K151E mutant (rVTT-A34Rmut) from VV Tiantan strain (VTT) with robustly increased EEV release was selected to serve as an optimized vaccine vector. 2018 Antiviral research Abstract HIV A34R;K151E 16;21 20;26 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Rilpivirine resistance was strongly associated with K103N especially in combination with other rilpivirine-associated mutations. 2018 Antiviral chemistry & chemotherapy Abstract HIV K103N 52 57 29575910 Short Communication: Characterization of a New HIV-1 Group N Isolate Originating from a Cameroonian Patient. However, the Vpu protein responsible for tetherin antagonism displayed the same amino acid substitutions (E15A, V19A, I25L, and V26L) as other HIV-1/N from Cameroon. 2018 AIDS research and human retroviruses Abstract HIV E15A;I25L;V19A;V26L 106;118;112;128 110;122;116;132 Vpu 13 16 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. Two (14% [95% CI 1.8%-42.8%]) G73S accessory mutations were detected in both transmitter and recipient. 2018 PLoS medicine Abstract HIV G73S 28 34 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Mutation of one strictly conserved RT residue (E300R) delayed reverse transcription and viral core uncoating and strongly inhibited HIV-1 replication in CD4+ T cells. 2018 mBio Abstract HIV E300R 47 52 RT;RT 62;35 83;37 29589465 Genotypic Characterization of Human Immunodeficiency Virus Type 1 Prevalent in Kepulauan Riau, Indonesia. Furthermore, major mutations, including M184V (2.2%) and Y188L (2.2%), were identified in the viral pol gene encoding reverse transcriptase derived from a study participant, suggesting that the prevalence of HIVDR is low in the region. 2018 AIDS research and human retroviruses Abstract HIV M184V;Y188L 40;57 45;62 RT;Pol 118;100 139;103 29595649 Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. All children had wild-type viruses through both Sanger sequencing and UDPS, except for 1 PMTCT-exposed infant harboring minority K103N (8.31%), born to a mother exposed to AZT+3TC+NVP. 2018 Medicine Abstract HIV K103N 129 134 29608685 Dolutegravir-based maintenance monotherapy versus dual therapy with lamivudine: a planned 24 week analysis of the DOLAM randomized clinical trial. Three patients (none previously exposed to integrase inhibitors) prematurely discontinued treatment due to viral failure: dolutegravir/lamivudine (n = 1), no resistance mutations (subject A); dolutegravir (n = 2), N155H, S147G and Q148R resistance mutations (subject B), and E138K, G140S and N155H resistance mutations (subject C). 2018 The Journal of antimicrobial chemotherapy Abstract HIV N155H;N155H;S147G 214;292;221 219;297;226 IN 43 52 29617822 HIV-1 Resistance Dynamics in Patients With Virologic Failure to Dolutegravir Maintenance Monotherapy. INSTI-RAMs (S230R, R263K, N155H, and E92Q+N155H) were detected in 4 patients, no INSTI-RAMs were detected in 4 patients, and sequencing of the integrase gene was unsuccessful in 2 patients. 2018 The Journal of infectious diseases Abstract HIV E92Q;N155H;N155H;R263K;S230R 37;26;42;19;12 41;31;47;24;17 IN;INSTI;INSTI 143;0;81 152;5;86 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. Conclusions: Our data indicate that the S230R substitution is comparable to the previously reported R263K substitution in some respects. 2018 The Journal of infectious diseases Abstract HIV R263K;S230R 100;40 105;45 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. Methods: We evaluated the effect of the S230R substitution in regard to integrase enzyme activity, viral infectivity, replicative capacity, and susceptibility to different INSTIs by biochemical and cell-based assays. 2018 The Journal of infectious diseases Abstract HIV S230R 40 45 IN;INSTI 72;172 81;178 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virologic failure while using DTG monotherapy. 2018 The Journal of infectious diseases Abstract HIV S230R 81 86 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. Resistance levels against DTG, cabotegravir, raltegravir, and elvitegravir in tissue culture were 3.85-, 3.72-, 1.52-, and 1.21-fold, respectively, in virus with the S230R substitution. 2018 The Journal of infectious diseases Abstract HIV S230R 166 171 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. Results: The S230R substitution conferred a 63% reduction in enzyme efficiency. 2018 The Journal of infectious diseases Abstract HIV S230R 13 18 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. S230R virus was 1.29-fold less infectious than wild-type virus but could replicate in PM1 cells without significant delay. 2018 The Journal of infectious diseases Abstract HIV S230R 0 5 29617824 The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors. Virologic failure during DTG monotherapy can occur through the development of the S230R or R263K mutation, without the need for high-level DTG resistance. 2018 The Journal of infectious diseases Abstract HIV R263K;S230R 91;82 96;87 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Genotypic susceptibility score-adjusted central nervous system (CNS) penetration-effectiveness (CPE) values were calculated for CSF escape with M184V/I mutations (n = 34). 2018 Clinical infectious diseases Abstract HIV M184I;M184V 144;144 151;151 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Plasma and CSF M184V/I combined with thymidine-analog mutations were more frequent in CSF escape vs no escape (23% vs 2.3%). 2018 Clinical infectious diseases Abstract HIV M184I;M184V 15;15 22;22 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Reduced CNS ART bioavailability may predispose to CSF escape in patients with M184V/I mutations. 2018 Clinical infectious diseases Abstract HIV M184I;M184V 78;78 85;85 29625416 Molecular dynamics and ligand docking of a hinge region variant of South African HIV-1 subtype C protease. However, the N37T V variant protease displayed a lower degree of anti-correlation. 2018 Journal of molecular graphics & modelling Abstract HIV N37T 13 17 PR 28 36 29625416 Molecular dynamics and ligand docking of a hinge region variant of South African HIV-1 subtype C protease. The mutations affected the thermodynamic landscape of inhibitor binding as there were fewer observable chemical contacts between the N37T V variant protease and lopinavir, atazanavir and darunavir, respectively. 2018 Journal of molecular graphics & modelling Abstract HIV N37T 133 137 PR 148 156 29625416 Molecular dynamics and ligand docking of a hinge region variant of South African HIV-1 subtype C protease. The results indicate that the N37T V hinge region mutation and insertion alter the molecular dynamics of the flap and hinge regions when compared to the wild-type protease. 2018 Journal of molecular graphics & modelling Abstract HIV N37T 30 34 PR 163 171 29625416 Molecular dynamics and ligand docking of a hinge region variant of South African HIV-1 subtype C protease. We performed molecular dynamics simulations and induced fit docking on a wild-type South African HIV-1 subtype C protease and an N37T V hinge region variant. 2018 Journal of molecular graphics & modelling Abstract HIV N37T 129 133 PR 113 121 29627709 Rare emergence of drug resistance in HIV-1 treatment-naive patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks. M184V/I was the most prevalent RAM (1.2% overall). 2018 Journal of clinical virology Abstract HIV M184I;M184V 0;0 7;7 29627709 Rare emergence of drug resistance in HIV-1 treatment-naive patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks. Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-RAMs [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-RAMs [0.9%], K65R/N [0.5%]). 2018 Journal of clinical virology Abstract HIV K65N;K65N;K65R;K65R;M184I;M184I;M184V;M184V 146;207;146;207;111;172;111;172 152;213;152;213;118;179;118;179 INSTI;INSTI 127;188 132;193 29631420 Prevalence of Integrase Strand Transfer Inhibitors Resistance Mutations in Integrase Strand Transfer Inhibitors-Naive and -Experienced HIV-1 Infected Patients: A Single Center Experience. A novel mutation at a recognized resistance site (E92K) was identified in one RAL-experienced patient. 2018 AIDS research and human retroviruses Abstract HIV E92K 50 54 29631420 Prevalence of Integrase Strand Transfer Inhibitors Resistance Mutations in Integrase Strand Transfer Inhibitors-Naive and -Experienced HIV-1 Infected Patients: A Single Center Experience. Among them, 10 harbored N155H, 4 Q148H, 2 Q148R, 2 Y143C/S, and 2 T66A/I/T, respectively. 2018 AIDS research and human retroviruses Abstract HIV T66A;T66I;T66T;Y143C;N155H 66;66;66;51;24 74;74;74;58;29 29631960 The design, synthesis and structure-activity relationships associated with C28 amine-based betulinic acid derivatives as inhibitors of HIV-1 maturation. Compared to the C-28 amide 3, 20 offers a 2- to 4-fold improvement in potency towards the screening viruses, exhibits low shifts in the EC50 values toward the V370A and DeltaV370 viruses in the presence of human serum or human serum albumin, and demonstrates improved potency towards the polymorphic T371A and V362I virus variants. 2018 Bioorganic & medicinal chemistry letters Abstract HIV DeltaV370;T371A;V362I;V370A 169;300;310;159 178;305;315;164 29633077 Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naive individuals. Among the drug-treated individuals, the results showed that K103N in the RT region was the most frequent mutation, found in 67% (6/9) of the cases, followed by M184V with 56% (5/9). 2018 Archives of virology Abstract HIV K103N;M184V 60;160 65;165 RT 73 75 29633077 Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naive individuals. K103N occurred at the highest rate, accounting for 22% (6/27), followed by P225H (7%) and Y188L (4%). 2018 Archives of virology Abstract HIV P225H;Y188L;K103N 75;90;0 80;95;5 29633077 Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naive individuals. Our study revealed that the prevalence of drug resistance was relatively high in Xinjiang and that K103N occurred at the highest rate. 2018 Archives of virology Abstract HIV K103N 99 104 29633077 Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naive individuals. These results suggest that it is important to carry out HIV drug resistance testing, especially for the K103N mutation in the RT region, before and during the treatment process. 2018 Archives of virology Abstract HIV K103N 104 109 RT 126 128 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Among this series, propionitrile (3b2, EC50(IIIB) = 0.020 muM, EC50(E138K) = 0.015 muM, CC50 = 40.15 muM), pyrrolidin-1-ylmethanone (3b8, EC50(IIIB) = 0.020 muM, EC50(E138K) = 0.014 muM, CC50 = 58.09 muM) and morpholinomethanone (3b9, EC50(IIIB) = 0.020 muM, EC50(E138K) = 0.027 muM, CC50 = 180.90 muM) derivatives are the three most promising compounds which are equally potent to the marketed drug Etravirine against E138K mutant strain but with much lower cytotoxicity. 2018 European journal of medicinal chemistry Abstract HIV E138K;E138K;E138K;E138K 419;68;167;264 424;73;172;269 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Evaluations of selected compounds against more drug-resistant strains showed these compounds had advantage of inhibiting E138K mutant virus which is a key drug-resistant mutant to the new generation of NNRTIs. 2018 European journal of medicinal chemistry Abstract HIV E138K 121 126 NNRTI 202 208 29635462 Low prevalence of transmitted HIV-1 drug resistance detected by a dried blood spot (DBS)-based next-generation sequencing (NGS) method in newly diagnosed individuals in Cameroon in the years 2015-16. The NNRTI mutation K103N was most commonly detected (2.7%). 2018 The Journal of antimicrobial chemotherapy Abstract HIV K103N 19 24 NNRTI 4 9 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. In addition, the modelling of PR1 mutant structures containing V32I and L76M substitutions revealed a cooperative mechanism leading to structural deformation of flap-residue 45 that could modify PR2 flexibility. 2018 Scientific reports Abstract HIV L76M;V32I 72;63 76;67 PR;PR 195;30 198;33 29641878 SURVEILLANCE OF HIV-1 DRUG-RESISTANCE MUTATIONS IN THAILAND FROM 1999 TO 2014. However, non-NRTI-associated mutations increased between 1999 and 2007,but have remained constant since, with Y181I/C the most (31.4%) prevalent. 2017 The Southeast Asian journal of tropical medicine and public health Abstract HIV Y181C;Y181I 110;110 117;117 NNRTI 9 17 29641878 SURVEILLANCE OF HIV-1 DRUG-RESISTANCE MUTATIONS IN THAILAND FROM 1999 TO 2014. M184I/V was the most common (53.1%prevalence) RT inhibitor (NRTI) mutation. 2017 The Southeast Asian journal of tropical medicine and public health Abstract HIV M184I;M184V 0;0 7;7 NRTI;RT 60;46 64;48 29641878 SURVEILLANCE OF HIV-1 DRUG-RESISTANCE MUTATIONS IN THAILAND FROM 1999 TO 2014. PRdrug-associated mutations (M36I/L/V, H69K/R and L89I/M/V) previously consideredas CRF01_AE polymorphisms constituted > 90% prevalence in all samples.The launch of antiretroviral treatment influenced the pattern of mutations and theUniversal Coverage Scheme also impacted the rate of development of resistancemutations on a national scale. 2017 The Southeast Asian journal of tropical medicine and public health Abstract HIV H69K;H69R;L89I;L89M;L89V;M36I;M36L;M36V 39;39;50;50;50;29;29;29 45;45;58;58;58;37;37;37 29643244 SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction between the Viral Capsid and Cellular Cyclophilin A. Downregulation of endogenous SUN1 inhibited the nuclear entry of the wild-type virus but not that of the G89A mutant. 2018 Journal of virology Abstract HIV G89A 105 109 29643244 SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction between the Viral Capsid and Cellular Cyclophilin A. Treatment of SUN1-expressing cells with cyclosporine (CsA) significantly reduced the sensitivity of the virus to SUN1, and an HIV-1 mutant containing CA-G89A, which does not interact with cyclophilin A (CypA), was resistant to SUN1 overexpression. 2018 Journal of virology Abstract HIV G89A 153 157 Capsid 150 152 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Interestingly, a CA mutation (N74D) altering virus engagement of host factors involved in nuclear transport does not alter the uncoating site at the NE but reduces the nuclear penetration depth. 2018 Cell host & microbe Abstract HIV N74D 30 34 Capsid 17 19 29651941 Identification of Adjacent NNRTI Binding Pocket in Multi-mutated HIV1- RT Enzyme Model: An in silico Study. METHODS: An in Silico model of HIV-1 RT enzyme with multiple mutations K103N, Y181C and Y188L was developed and evaluated. 2018 Current HIV research Abstract HIV K103N;Y181C;Y188L 71;78;88 76;83;93 RT 37 39 29651941 Identification of Adjacent NNRTI Binding Pocket in Multi-mutated HIV1- RT Enzyme Model: An in silico Study. Mutations Y181C and Y188L prevented NNRTI binding by eliminating aromatic pi interactions offered by tyrosine rings. 2018 Current HIV research Abstract HIV Y181C;Y188L 10;20 15;25 NNRTI;PI 36;74 41;76 29651941 Identification of Adjacent NNRTI Binding Pocket in Multi-mutated HIV1- RT Enzyme Model: An in silico Study. RESULT AND DISCUSSION: K103N mutation narrowed the entrance of NNRTI binding pocket and forbade electrostatic interaction with alpha amino group of LYS103. 2018 Current HIV research Abstract HIV K103N 23 28 NNRTI 63 68 29652972 [Genetic analysis of the mutations in HIV-1 infected population in Ecuador]. Results The most frequent mutations were M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M, V82T/F/A/S/L and L90M in adults and F77L, K103N/S, M46L/I, V82T/F/A/S/L and L90M in children. 2018 Revista chilena de infectologia Abstract HIV D30N;F77L;I54L;I54M;K101E;K101H;K101P;K103N;K103N;K103S;K103S;L90M;L90M;M184I;M184V;M46I;M46I;M46L;M46L;V82A;V82A;V82F;V82F;V82L;V82L;V82S;V82S;V82T;V82T 70;128;84;84;50;50;50;61;134;61;134;109;168;41;41;76;143;76;143;92;151;92;151;92;151;92;151;92;151 74;132;90;90;59;59;59;68;141;68;141;113;172;48;48;82;149;82;149;104;163;104;163;104;163;104;163;104;163 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. CONCLUSIONS: The Q151M and T69i resistance mutations are now very rare in the UK. 2018 AIDS research and therapy Abstract HIV Q151M 17 22 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. 2018 AIDS research and therapy Abstract HIV Q151M;Q151M 23;140 28;145 PR 257 265 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. RESULTS: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. 2018 AIDS research and therapy Abstract HIV Q151M 38 43 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. 2018 AIDS research and therapy Abstract HIV Q151M 113 118 PR 211 219 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations. 2018 AIDS research and therapy Abstract HIV Q151M 4 9 RT;RT 69;154 90;175 29670696 Discovery of Novel Diarylpyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the "NNRTI Adjacent" Binding Site. Especially, 20 showed marked antiviral activity, which was 1.5-fold greater against WT and 1.5- to 3-fold greater against L100I, K103N, Y181C, Y188L, and E138K when compared with ETV. 2018 ACS medicinal chemistry letters Abstract HIV E138K;K103N;L100I;Y181C;Y188L 154;129;122;136;143 159;134;127;141;148 29672676 A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa. The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48. 2018 Clinical infectious diseases Abstract HIV G140S;K65R;Q148R 127;100;137 132;104;142 RT;IN 68;106 89;115 29683855 A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. One patient (D/C/F/TAF) was identified with M184I/V conferring resistance to emtricitabine. 2018 AIDS (London, England) Abstract HIV M184I;M184V 44;44 51;51 29683856 Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination. On day 2, HIV-1 RNA was 27 316 copies/ml, genotyping revealed M184V, K70T, K65R, and K103N mutations, plasma TFV and FTC concentrations were consistent with recent dosing. 2018 AIDS (London, England) Abstract HIV K103N;K65R;K70T;M184V 85;75;69;62 90;79;73;67 29684083 HIV-1 transmission networks across Cyprus (2010-2012). There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with sub-subtype A2 strain, both with PI drug resistance mutation M46L and one from Greece with sub-subtype A1 with non-nucleoside reverse transcriptase inhibitors (NNRTI) drug resistance mutation K103N. 2018 PloS one Abstract HIV K103N;M46L 385;254 390;258 NNRTI;NNRTI;PI 353;304;226 358;340;228 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. K103N was detected in two patients and T68D and T215D in one person each, corresponding to a prevalence of 0%, 1.2%, and 1.2% of TDR to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs), respectively. 2018 PloS one Abstract HIV T215D;T68D;K103N 48;39;0 53;43;5 NRTI;NNRTI;PR;NNRTI;NRTI;PI 163;220;136;231;208;157 195;229;144;237;213;160 29699924 Design, synthesis and biological evaluation of substituted (+)-SG-1 derivatives as novel anti-HIV agents. The result showed that RT- E138K/M184V mutant virus conferred 4.7-9.1-fold resistance to 4c, 4f, 2 and 6b, but only showed slight resistance to 4b (2-fold) which was better than SG-1. 2018 Bioorganic & medicinal chemistry letters Abstract HIV E138K;M184V 27;33 32;38 RT 23 25 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. The most frequent WHO-defined DRMs were NRTI: codon T215 (3.0%), NNRTI: K103N/S (4%), and PI: L90 (1%). 2018 AIDS research and human retroviruses Abstract HIV K103N;K103S 72;72 79;79 NNRTI;NRTI;PI 65;40;90 70;44;92 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. The most frequently detected IAS-USA-defined DRMs by class were NNRTI: K103N/S (4%), NRTI: M41L (1.5%), and PI: L90M (1%). 2018 AIDS research and human retroviruses Abstract HIV K103N;K103S;L90M;M41L 71;71;112;91 78;78;116;95 NNRTI;NRTI;PI 64;85;108 69;89;110 29732907 Prevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana. Prevalence of RPV and ETR highest DRM in the adult ART study (n = 41) were K101E (26.2%), E138A (23.8%), and Y181C (26.2%). 2018 AIDS research and human retroviruses Abstract HIV E138A;K101E;Y181C 90;75;109 95;80;114 29732907 Prevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana. The PMTCT cohort's (n = 127) high prevalence mutations were Y181C (15.7%), E138A (15%), and K101E (11%). 2018 AIDS research and human retroviruses Abstract HIV E138A;K101E;Y181C 75;92;60 80;97;65 29732988 Appearance of Drug Resistance Mutations Among the Dominant HIV-1 Subtype, CRF01_AE in Maumere, Indonesia. The major drug resistance-associated mutations, M184V, K103N, Y188L, and M230I, were found in the RT genes. 2018 Current HIV research Abstract HIV K103N;M184V;M230I;Y188L 55;48;73;62 60;53;78;67 RT 98 100 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. The resistant mutations covered several types, including one type of PI mutations (L33F), six types of NRTI mutations and seven types of NNRTI. 2018 BMC infectious diseases Abstract HIV L33F 83 87 NNRTI;NRTI;PI 137;103;69 142;107;71 29753024 Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase. This study reveals the antiretroviral efficacy of obtained two best ligands and delivers the hits against HIV-1 reverse transcriptase Q151M mutant. 2018 Infection, genetics and evolution Abstract HIV Q151M 134 139 RT 112 133 29753024 Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase. To discover potential hits, we docked 49 antiretroviral analogs (n = 6294) against HIV-1 reverse transcriptase Q151M mutant & its wild-type form and narrow downed their number in three sequential modes of docking using Schrodinger suite. 2018 Infection, genetics and evolution Abstract HIV Q151M 111 116 RT 89 110 29756454 Short Communication: Discordance in Drug Resistance Mutations Between Blood Plasma and Semen or Rectal Secretions Among Newly Diagnosed HIV-1-Infected Thai Men Who Have Sex with Men. Three participants had DRAMs in anogenital compartments that were not detected in blood plasma-one had DRAMs in semen that was not detected in blood plasma (I54FI) and two had DRAMs in rectal secretions that was not detected in blood plasma (I47IM; K70N, L74I, Y115F, M184V, K103N, V108I, and H221Y). 2018 AIDS research and human retroviruses Abstract HIV H221Y;I47I;I47M;I54F;I54I;K103N;K70N;L74I;M184V;V108I;Y115F 293;242;242;157;157;275;249;255;268;282;261 298;247;247;162;162;280;253;259;273;287;266 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. Although it is unclear whether these targets are related to later neutralization breadth development, the G460a target but not N462 glycan appeared more common in macaques with breadth than those without. 2018 Viruses Abstract HIV G460A 106 111 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. The targets of initial autologous neutralizing antibodies, arising between 10 and 20 weeks post infection, were mapped to N462 glycan and G460a in gp120 V5 in GB40 and FF69, respectively. 2018 Viruses Abstract HIV G460A 138 143 gp120 147 152 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Binding to cyclin T1 showed decreased binding of all Ser-16 and Ser-46 Tat mutants with S16D and Tat S46D mutationts showing the strongest effect. 2018 Retrovirology Abstract HIV S16D;S46D 88;101 92;105 Tat;Tat 71;97 74;100 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. HIV-1 proviral transcription was inhibited by Tat alanine mutants and partially restored by S16E mutation. 2018 Retrovirology Abstract HIV S16E 92 96 Tat 46 49 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Pseudotyped HIV-1 with Tat S16E mutation replicated well, and HIV-1 Tat S46E-poorly, but no live viruses were obtained with Tat S16A or Tat S46A mutations. 2018 Retrovirology Abstract HIV S16A;S16E;S46A;S46E 128;27;140;72 132;31;144;83 Tat;Tat;Tat;Tat 23;68;124;136 26;71;127;139 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. TAR RNA binding was affected by Tat Ser-16 alanine mutation. 2018 Retrovirology Abstract HIV S16A 36 50 Tat 32 35 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The results showed that the most frequent amino acid substitutions in RT were L214F (67.6%), I135T (55.9%), and in PR was V15I (41.2%). 2018 Scientific reports Abstract HIV I135T;L214F;V15I 93;78;122 98;83;126 RT;PR 70;115 72;117 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The thymidine analogue mutations, M184V/I and the tenofovir-associated DRMs K65R and K70E/Q/G/N/T accounted for 82.9%, 7.3%, and 1.4% of NRTI-associated TDR, respectively. 2019 Clinical infectious diseases Abstract HIV K65R;K70E;K70G;K70N;K70Q;K70T;M184I;M184V 76;85;85;85;85;85;34;34 80;97;97;97;97;97;41;41 NRTI 137 141 29846602 Prevalence of drug resistance in children recently diagnosed with HIV-1 infection in France (2006-17): impact on susceptibility to first-line strategies. Additionally, 3/60 (5%) strains had integrase inhibitor (INI)-related RAMs (an isolated E157Q mutation, which could mostly affect the susceptibility to raltegravir/elvitegravir rather than that to dolutegravir). 2018 The Journal of antimicrobial chemotherapy Abstract HIV E157Q 88 93 IN;IN 36;57 45;60 29847122 Consistent Prediction of Mutation Effect on Drug Binding in HIV-1 Protease Using Alchemical Calculations. In this study, we analyze ten different protease-inhibitor complexes carrying major resistance-associated mutations (RAMs) G48V, I50V, and L90M using molecular dynamics simulations. 2018 Journal of chemical theory and computation Abstract HIV G48V;I50V;L90M 121;129;139 127;133;143 PR 40 48 29873733 Prevalence and clinical impact of minority resistant variants in patients failing an integrase inhibitor-based regimen by ultra-deep sequencing. Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%). 2018 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148K;Q148R;T97A;Y143C 141;154;154;154;171;186 146;163;163;163;175;191 INSTI 109 114 29875244 HIV-1 Protease Evolvability Is Affected by Synonymous Nucleotide Recoding. However, the WT and MAX virus proteases showed different resistance variant repertoires, with the G16E and V77I substitutions observed only in the WT and the L33F, S37P, G48L, Q58E/K, and L89I substitutions detected only in the MAX virus. 2018 Journal of virology Abstract HIV G16E;G48L;L33F;L89I;Q58E;Q58K;S37P;V77I 98;170;158;188;176;176;164;107 102;174;162;192;182;182;168;111 PR 30 39 29875244 HIV-1 Protease Evolvability Is Affected by Synonymous Nucleotide Recoding. Remarkably, the G48L and L89I substitutions are rarely found in vivo in PI-treated patients. 2018 Journal of virology Abstract HIV G48L;L89I 16;25 20;29 PI 72 74 29875245 HIV-1 gp41 Residues Modulate CD4-Induced Conformational Changes in the Envelope Glycoprotein and Evolution of a Relaxed Conformation of gp120. While all Envs show increased neutralization sensitivity to mimetic CD4 (mCD4), Envs with either the E560K or Q577R HR1 mutation reduced conformational reactivity to CD4 that resisted viral inactivation and triggering to the 6HB. 2018 Journal of virology Abstract HIV E560K;Q577R 101;110 106;115 Env;Env 10;80 14;84 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. Primary INSTIs resistance mutation were absent, however secondary mutations L74IM, T97A were detected in four samples (5.2%). 2018 BMC research notes Abstract HIV L74I;L74M;T97A 76;76;83 81;81;87 INSTI 8 14 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. The most common emergent RAMs to NRTIs were M184V/I (42.3%) and K65R (28.2%), and those to nNRTIs were Y181C (42.3%), K103N (15.5%), G190A/E/Q (12.7%), V179D/E (12.7%), and V108I (9.9%). 2018 Infection and drug resistance Abstract HIV G190A;G190E;G190Q;K103N;K65R;M184I;M184V;V108I;V179D;V179E;Y181C 133;133;133;118;64;44;44;173;152;152;103 142;142;142;123;68;51;51;178;159;159;108 NNRTI;NRTI 91;33 97;38 29894388 Durable suppression of HIV-1 with resistance mutations to integrase inhibitors by dolutegravir following drug washout. DESIGN AND METHODS: MT-2 cells infected with wild-type, R263K or G140S/Q148H HIV-1 clones were treated with DTG, RAL or EVG for 3 days. 2018 AIDS (London, England) Abstract HIV G140S;Q148H;R263K 65;71;56 70;76;61 29894388 Durable suppression of HIV-1 with resistance mutations to integrase inhibitors by dolutegravir following drug washout. Now, we performed DTG, EVG and RAL washout experiments to compare the recovery of viral integration and production of 2-long terminal repeat (LTR) circles using wild-type HIV-1 clones, R263K viruses with low-level resistance to DTG and viruses with G140S/Q148H mutations showing cross-resistance against all currently approved INSTIs. 2018 AIDS (London, England) Abstract HIV G140S;Q148H;R263K 249;255;185 254;260;190 LTR;INSTI;LTR 120;327;142 140;333;145 29894388 Durable suppression of HIV-1 with resistance mutations to integrase inhibitors by dolutegravir following drug washout. RESULTS: Viral integration did not resume for up to 8 days after DTG washout from the wild-type or R263K infections but increased soon after washout of either RAL or EVG. 2018 AIDS (London, England) Abstract HIV R263K 99 104 29894388 Durable suppression of HIV-1 with resistance mutations to integrase inhibitors by dolutegravir following drug washout. With the G140S/Q148H virus, levels of integration were not significantly affected by the presence of either RAL or EVG. 2018 AIDS (London, England) Abstract HIV G140S;Q148H 9;15 14;20 29905958 Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia. From non-nucleoside reverse transcriptase inhibitor mutations, G190S was shown to be the most prevalent (49.4%), followed by K101E (27.10%) and K103N (24.4%). 2019 Journal of medical virology Abstract HIV G190S;K101E;K103N 63;125;144 68;130;149 NNRTI 5 41 29905958 Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia. G190S and K101E were more common in subtype A as compared with non-A viruses (G190S: 54.9% vs 11.3%, P < 0.0001; K101E: 29.8% vs 11.3%, P = 0.005). 2019 Journal of medical virology Abstract HIV G190S;K101E;K101E;G190S 78;10;113;0 83;15;118;5 29905958 Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia. K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed. 2019 Journal of medical virology Abstract HIV K65R 0 4 29905958 Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia. On the other hand, K103N was more frequent in non-A subtypes (43.4%) compared with subtype A (22.2%), P = 0.0008. 2019 Journal of medical virology Abstract HIV K103N 19 24 29905958 Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia. The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%). 2019 Journal of medical virology Abstract HIV K65R;L74V;M184V 91;108;76 95;112;81 NRTI 18 50 29915897 Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Resistance did not emerge to the STR components, with the exception being an emtricitabine resistance-associated mutation (RAM) [M184I/V] in one of seven recipients who experienced virological failure (although M184V was a minority variant at screening in this patient). 2018 Drugs Abstract HIV M184I;M184V;M184V 129;129;211 136;136;216 29929981 Molecular mechanism of HIV-1 resistance to sifuvirtide, a clinical trial-approved membrane fusion inhibitor. Importantly, whereas the V38A and Q52R substitutions disrupted the N-terminal helix of gp41, a single A47I substitution greatly enhanced its thermostability. 2018 The Journal of biological chemistry Abstract HIV A47I;Q52R;V38A 102;34;25 106;38;29 gp41 87 91 29929981 Molecular mechanism of HIV-1 resistance to sifuvirtide, a clinical trial-approved membrane fusion inhibitor. Three primary substitutions (V38A, A47I, and Q52R) located at the inhibitor-binding site of HIV-1's envelope protein (Env) and one secondary substitution (N126K) located at the C-terminal heptad repeat region of the viral protein gp41, which is part of the envelope, conferred high SFT resistance and cross-resistance to the anti-HIV-1 drug T20 and the template peptide C34. 2018 The Journal of biological chemistry Abstract HIV A47I;N126K;Q52R;V38A 35;155;45;29 39;160;49;33 Env;Env;gp41;Env 100;257;230;118 108;265;234;121 29929981 Molecular mechanism of HIV-1 resistance to sifuvirtide, a clinical trial-approved membrane fusion inhibitor. We found that the V38A and Q52R substitutions reduce the binding stabilities of SFT, C34, and MTSFT, but they had no effect on the binding of 2P23 and LP-19; in sharp contrast, the A47I substitution enhanced fusion inhibitor binding. 2018 The Journal of biological chemistry Abstract HIV A47I;Q52R;V38A 181;27;18 185;31;22 29947629 Prediction of the binding mode and resistance profile for a dual-target pyrrolyl diketo acid scaffold against HIV-1 integrase and reverse-transcriptase-associated ribonuclease H. The results demonstrated that only three mutations in HIV-1 IN (Y143C, Q148R and N155H) and two mutations in HIV-1 RNase H (Y501R and Y501W) resulted in a reduction of JMC6F potency, thus indicating their potential role in providing resistance to JMC6F. 2018 Physical chemistry chemical physics Abstract HIV N155H;Q148R;Y143C;Y501R;Y501W 81;71;64;124;134 86;76;69;130;139 IN 60 62 29968678 A substrate selected by phage display exhibits enhanced side-chain hydrogen bonding to HIV-1 protease. The crystal structure of the complex between this substrate and the D25N variant of the protease is reported at a resolution of 1.1 A. 2018 Acta crystallographica. Section D, Structural biology Abstract HIV D25N 68 72 PR 88 96 29973007 [Study on the relationship between HIV drug resistance and CD4(+)T cell counts among antiretroviral therapy patients with low viral load]. The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). 2018 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV M184I;M184V 33;33 40;40 NNRTI 42 47 29973007 [Study on the relationship between HIV drug resistance and CD4(+)T cell counts among antiretroviral therapy patients with low viral load]. The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. 2018 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV V32E;V32L;V82A 18;18;34 24;24;38 PI;PI 26;40 28;42 29973007 [Study on the relationship between HIV drug resistance and CD4(+)T cell counts among antiretroviral therapy patients with low viral load]. The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). 2018 Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] Abstract HIV K103N 19 24 NNRTI 26 31 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The difference was mainly due to the high prevalence of minority K65R and M184I mutations. 2018 African journal of laboratory medicine Abstract HIV K65R;M184I 65;74 69;79 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. BACKGROUND: Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. 2018 Open forum infectious diseases Abstract HIV M184V 228 233 PR 43 51 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. CONCLUSIONS: Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips. 2018 Open forum infectious diseases Abstract HIV M184V 35 40 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (P = .016). 2018 Open forum infectious diseases Abstract HIV M184V;M184V;M184V 100;279;324 105;284;329 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. 2018 Open forum infectious diseases Abstract HIV M184V;M184V 14;224 19;229 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (P = .323). 2018 Open forum infectious diseases Abstract HIV M184V;M184V 109;150 114;155 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. 2018 Open forum infectious diseases Abstract HIV M184V 102 107 29991591 Template-primer binding affinity and RNase H cleavage specificity contribute to the strand transfer efficiency of HIV-1 reverse transcriptase. Although L92P also deleteriously affected the RT's nontemplated nucleotide addition activity, neither nontemplated nucleotide addition activity nor the RT's clamp activities contributed to increased template switching when all tested mutant and WT RTs were considered. 2018 The Journal of biological chemistry Abstract HIV L92P 9 13 RT;RT;RT 46;152;248 48;154;251 29991591 Template-primer binding affinity and RNase H cleavage specificity contribute to the strand transfer efficiency of HIV-1 reverse transcriptase. Now, we found that RTs containing RNase H-inactivating mutations (D443N or E478Q) were devoid of strand transfer activity, whereas enzymes containing F61A or L92P had very low strand transfer activity. 2018 The Journal of biological chemistry Abstract HIV D443N;E478Q;F61A;L92P 66;75;150;158 72;80;154;162 RT 19 22 29991591 Template-primer binding affinity and RNase H cleavage specificity contribute to the strand transfer efficiency of HIV-1 reverse transcriptase. The highest strand transfer efficiencies were obtained with HIV-1ESP49 RT mutants containing the substitutions K358R/A359G/S360A, alone or in combination with V148I or T355A/Q357M. 2018 The Journal of biological chemistry Abstract HIV A359G;K358R;S360A;Q357M;T355A;V148I 117;111;123;174;168;159 122;116;128;179;173;164 RT 71 73 29991591 Template-primer binding affinity and RNase H cleavage specificity contribute to the strand transfer efficiency of HIV-1 reverse transcriptase. The strand transfer defect produced by L92P was attributed to a loss of template-primer binding affinity and, more specifically, to the higher dissociation rate constants (koff) shown by RTs bearing this substitution. 2018 The Journal of biological chemistry Abstract HIV L92P 39 43 RT 187 190 29997209 Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection. The polymorphisms V241I, I257V, P272K, and E297K in reverse transcriptase and I201V in integrase, all relatively uncommon polymorphisms occurring in or adjacent to optimally described HLA-restricted cytotoxic T-lymphocyte epitopes, were associated with reduced RC. 2018 Journal of virology Abstract HIV E297K;I201V;I257V;P272K;V241I 43;78;25;32;18 48;83;30;37;23 RT;IN 52;87 73;96 29997211 Nup153 Unlocks the Nuclear Pore Complex for HIV-1 Nuclear Translocation in Nondividing Cells. Analysis of integration sites in HIV-1 viruses with N57 mutations revealed diminished integration into transcriptionally active genes in a manner resembling that of HIV-1 in CPSF6 knockout cells or that of HIV-1-N74D. 2018 Journal of virology Abstract HIV N74D 212 216 30010985 Accumulation of Multiple Mutations In Vivo Confers Cross-Resistance to New and Existing Integrase Inhibitors. The combination of major integrase inhibitor substitutions G140S/Q148H has been shown to confer high-level resistance to the approved integrase inhibitors raltegravir (RAL) and elvitegravir (EVG) but not necessarily dolutegravir (DTG). 2018 The Journal of infectious diseases Abstract HIV G140S;Q148H 59;65 64;70 IN;IN 25;134 34;143 30010985 Accumulation of Multiple Mutations In Vivo Confers Cross-Resistance to New and Existing Integrase Inhibitors. We assayed recombinant viruses made from patient-derived RNA extracts for resistance phenotype for a panel of viruses containing G140S/Q148H with additional accessory substitutions. 2018 The Journal of infectious diseases Abstract HIV G140S;Q148H 129;135 134;140 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. Five isolates had secondary mutations to protease inhibitors (K20M, L10V, L33I, A71T, A71V). 2018 PloS one Abstract HIV A71T;A71V;K20M;L10V;L33I 80;86;62;68;74 84;90;66;72;78 PR 41 49 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. Isolates from two participants showed mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI) only (M41L, T125C, T125F, M184V), while an isolate from one patient who had received antiretroviral therapy (ART) since 2008 had a mutation associated with resistance to non-NRTI (G190S). 2018 PloS one Abstract HIV G190S;M184V;M41L;T125C;T125F 309;155;135;141;148 314;160;139;146;153 NRTI;NNRTI;NRTI 123;299;78 127;307;110 30021898 SOSIP Changes Affect Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Conformation and CD4 Engagement. Here we compare the impact on the membrane Env conformation of the SOSIP changes with that of the well-characterized changes (L193R and I423A) that shift Env to downstream States 2 and 3. 2018 Journal of virology Abstract HIV I423A;L193R 136;126 141;132 Env;Env 43;154 46;157 30021898 SOSIP Changes Affect Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Conformation and CD4 Engagement. Most structural studies of Env trimers have utilized truncated soluble gp140 Envs stabilized with the I559P and SOS changes. 2018 Journal of virology Abstract HIV I559P 102 107 gp140;Env;Env 71;27;77 76;30;81 30021898 SOSIP Changes Affect Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Conformation and CD4 Engagement. The introduction of an artificial disulfide bond linking the gp120 and gp41 subunits (SOS) in combination with the I559P (IP) change has allowed structural characterization of soluble gp140 (sgp140) trimers. 2018 Journal of virology Abstract HIV I559P 115 120 gp120;gp140;gp41 61;184;71 66;189;75 30021898 SOSIP Changes Affect Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Conformation and CD4 Engagement. The results presented here suggest that the SOSIP changes stabilize Env in a conformation that differs from State 1 but also from the downstream Env conformations stabilized by L193R or I423A.IMPORTANCE The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer is triggered by receptor binding to mediate the entry of the virus into cells. 2018 Journal of virology Abstract HIV I423A;L193R 186;177 191;182 Env;Env;Env;Env 251;68;145;274 259;71;148;277 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. A62V was found to increase the observed lower mutant frequency identified with each of the viruses harboring the MDR mutation complexes in the single-cycle assay. 2018 Viruses Abstract HIV A62V 0 4 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Furthermore, A62V was observed to improve viral fitness of replication-competent MDR viruses. 2018 Viruses Abstract HIV A62V 13 17 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In particular, A62V was observed in various multi-dideoxynucleoside resistant (MDR) mutation complexes, including the Q151M complex (i.e., A62V, V75I, F77L, F116Y, and Q151M), and the T69SSS insertion complex, which has a serine-serine insertion between amino acid positions 69 and 70 (i.e., M41L, A62V, T69SSS, K70R, and T215Y). 2018 Viruses Abstract HIV A62V;A62V;A62V;F116Y;F77L;K70R;M41L;Q151M;Q151M;T215Y;T69SSS;T69SSS;V75I 15;139;298;157;151;312;292;118;168;322;184;304;145 19;143;302;162;155;316;296;123;173;327;190;310;149 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In this study, we hypothesized that A62V could influence replication fidelity and viral fitness with viruses harboring the Q151M and T69SSS MDR mutation complexes. 2018 Viruses Abstract HIV A62V;Q151M;T69SSS 36;123;133 40;128;139 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Taken together, these observations indicate an adaptive role of A62V in virus replication fidelity and viral fitness, which would likely enhance virus persistence during drug-selective pressure. 2018 Viruses Abstract HIV A62V 64 68 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The A62V amino acid substitution in HIV-1 reverse transcriptase (RT) was observed to be associated with multi-drug resistance, but is not known to be a resistance-conferring mutation. 2018 Viruses Abstract HIV A62V 4 8 RT;RT 42;65 63;67 30032194 Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir. Methods: The frequency of eight substitutions associated with decreased susceptibility to fostemsavir (L116P, A204D, S375M/H, M426L, M434I, M475I and V506M), was investigated in 111 gp120 sequences from groups O (n = 100), N (n = 9) and P (n = 2). 2018 The Journal of antimicrobial chemotherapy Abstract HIV A204D;L116P;M426L;M434I;M475I;S375H;S375M;V506M 110;103;126;133;140;117;117;150 115;108;131;138;145;124;124;155 gp120 182 187 30032194 Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir. Results: All HIV-1 group N sequences harboured the three substitutions S375M, M426L and M434I, whereas only 1% and 10% of HIV-1 group O sequences harboured the S375H + M426L and S375H + M434I patterns, respectively. 2018 The Journal of antimicrobial chemotherapy Abstract HIV M426L;M426L;M434I;M434I;S375H;S375H;S375M 78;168;88;186;160;178;71 83;173;93;191;165;183;76 30032194 Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir. The main genetic profile of HIV-1 groups P and O combined S375H with two atypical substitutions (M426S and M434L). 2018 The Journal of antimicrobial chemotherapy Abstract HIV M426S;M434L;S375H 97;107;58 103;112;63 30047788 Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation. All patients had a baseline M184V/I mutation, with 10 (31%) having resistance to TDF; 27 (84%) achieved a VL <200 cp/mL, and 25(78%) had a VL <200 cp/mL at the last reading; 22 (69%) achieved a VL <40 cp/mL. 2019 The Annals of pharmacotherapy Abstract HIV M184I;M184V 28;28 35;35 30047788 Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation. METHODS: This was a single-center chart review of HIV-infected patients receiving daily TDF/FTC plus DRV/r and identified with resistant virus (including, but not limited to, an M184V/I). 2019 The Annals of pharmacotherapy Abstract HIV M184I;M184V 178;178 185;185 HIV infections 50 62 30047788 Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation. These retrospective data suggest that despite the presence of an M184V/I, this combination may be an option in patients seeking a once-daily ARV therapy to improve adherence. 2019 The Annals of pharmacotherapy Abstract HIV M184I;M184V 65;65 72;72 30051758 Exploring the drug resistance mechanism of active site, non-active site mutations and their cooperative effects in CRF01_AE HIV-1 protease: molecular dynamics simulations and free energy calculations. In this work, we have investigated the mechanism of resistance against indinavir (IDV) due to therapy selected active site mutation V82F, non-active site mutations PF82V and their cooperative effects PV82F in subtype AE-protease using molecular dynamics simulations and binding free energy calculations. 2019 Journal of biomolecular structure & dynamics Abstract HIV V82F 132 136 PR 220 228 30051758 Exploring the drug resistance mechanism of active site, non-active site mutations and their cooperative effects in CRF01_AE HIV-1 protease: molecular dynamics simulations and free energy calculations. Large positional deviation of IDV was observed in V82F complex. 2019 Journal of biomolecular structure & dynamics Abstract HIV V82F 50 54 30051758 Exploring the drug resistance mechanism of active site, non-active site mutations and their cooperative effects in CRF01_AE HIV-1 protease: molecular dynamics simulations and free energy calculations. The simulations suggested all the three complexes lead to decrease in binding affinity of IDV, whereas the PF82V complex resulted in an enhanced binding affinity compared to V82F and PV82F complexes. 2019 Journal of biomolecular structure & dynamics Abstract HIV V82F 174 178 30056211 Binding of host factors to stabilized HIV-1 capsid tubes. In this assay, we took advantage of the HIV-1 capsid mutant A14C/E45C protein, which is stabilized by disulfide bonds, and is resistant to washing steps. 2018 Virology Abstract HIV A14C;E45C 60;65 64;69 Capsid 46 52 30060027 Evolution of Protease Inhibitor Resistance in Human Immunodeficiency Virus Type 1 Infected Patients Failing Protease Inhibitor Monotherapy as Second-line Therapy in Low-income Countries: An Observational Analysis Within the EARNEST Randomized Trial. Common PI mutations were M46I, I54V, and V82A. 2019 Clinical infectious diseases Abstract HIV I54V;M46I;V82A 31;25;41 35;29;45 PI 7 9 30060027 Evolution of Protease Inhibitor Resistance in Human Immunodeficiency Virus Type 1 Infected Patients Failing Protease Inhibitor Monotherapy as Second-line Therapy in Low-income Countries: An Observational Analysis Within the EARNEST Randomized Trial. VL changes were modest, mainly driven by nonadherence (P = .006) and PI mutation development (P = .0002); I47A was associated with a larger increase in VL than other mutations (P = .05). 2019 Clinical infectious diseases Abstract HIV I47A 106 110 PI 69 71 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. Major NRTI mutations were detected in 11 patient samples, which included M184V (n = 6), M41L (n=3), D67N (n=2), K219Q (n=3) and T215F (n=2). 2018 The Pan African medical journal Abstract HIV D67N;K219Q;M184V;M41L;T215F 100;112;73;88;128 104;117;78;92;133 NRTI 6 10 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. They included K103N (n = 10), G190A (n = 1), Y181C (n = 1) and Y188L (n = 1). 2018 The Pan African medical journal Abstract HIV G190A;K103N;Y181C;Y188L 30;14;45;63 35;19;50;68 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Accordingly, we performed a proline (P) substitution screen in the gp41 heptad repeat 1 region, identifying other trimer-enhancing Ps, including L555P. 2018 Frontiers in immunology Abstract HIV L555P 145 150 gp41 67 71 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Next, we screened 15 structure-guided potential cysteine pairs in gp140 and found that A501C-L663C ("CC2") forms an inter-protomer disulfide bond that demonstrably increased NFL trimer thermostability. 2018 Frontiers in immunology Abstract HIV A501C;L663C 87;93 92;98 gp140 66 71 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. This P improved trimer integrity compared to I559P in selected properties. 2018 Frontiers in immunology Abstract HIV I559P 45 50 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. M184V was the most frequent and was associated with highlevel resistance to 3TC, FTC, and ABC. 2018 Journal of public health in Africa Abstract HIV M184V 0 5 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Other mutations such as T215F/Y, D67N/E, K70R, and K219Q were associated with intermediate resistance to TDF, AZT, and 3TC. 2018 Journal of public health in Africa Abstract HIV D67E;D67N;K219Q;K70R;T215F;T215Y 33;33;51;41;24;24 39;39;56;45;31;31 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. We showed that the inhibitory effect of a mutant Vpr (H71R), which is unable to arrest the cell cycle, was significantly relieved compared with that of wild-type Vpr, suggesting that Vpr suppresses L1 mobility in a cell cycle dependent manner. 2018 Nucleic acids research Abstract HIV H71R 54 58 Vpr;Vpr;Vpr 49;162;183 52;165;186 30089694 PF74 Reinforces the HIV-1 Capsid To Impair Reverse Transcription-Induced Uncoating. At a PF74 concentration of 10 muM, the mechanical stability of the core is increased to a level similar to that of the intrinsically hyperstable capsid mutant E45A. 2018 Journal of virology Abstract HIV E45A 159 163 Capsid 145 151 30103267 New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T). In all cases but four, M184L and M184T mutations were present during NRTI treatment. 2019 Chemical biology & drug design Abstract HIV M184L;M184T 23;33 28;38 NRTI 69 73 30103267 New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T). Molecular recognition studies on M184L and M184T structures showed both FTC and 3TC thermodynamic profiles unfavorable in comparison with the wild-type sequence, corroborated by molecular dynamic simulations (MDS). 2019 Chemical biology & drug design Abstract HIV M184L;M184T 33;43 38;48 30103267 New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T). Mutations at HIV-1 reverse transcriptase (RT) codon 184 such as M184V confer resistance to two nucleos(t)ide RT inhibitors (NRTI), lamivudine (3TC) and emtricitabine (FTC). 2019 Chemical biology & drug design Abstract HIV M184V 64 69 RT;NRTI;RT;RT 19;124;42;109 40;128;44;111 30103267 New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T). The mutations M184L and M184T have been observed only in TE patients. 2019 Chemical biology & drug design Abstract HIV M184L;M184T 14;24 19;29 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. EVG-resistant viruses (T66I/R263K, T66I/E157Q/R263K, and S153A/R263K) retained residual susceptibility when switched to DTG, BIC or CAB, losing T66I by week 27. 2018 Retrovirology Abstract HIV E157Q;R263K;R263K;R263K;S153A;T66I;T66I;T66I 40;28;46;63;57;23;35;144 45;33;51;68;62;27;39;148 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Here, in vitro drug selections compared the development of resistance to DTG, BIC, CAB, EVG and RAL using clinical isolates from treatment-naive primary HIV infection (PHI) cohort participants (n = 12), and pNL4.3 recombinant strains encoding patient-derived Integrase with (n = 5) and without (n = 5) the E157Q substitution. 2018 Retrovirology Abstract HIV E157Q 306 311 IN 259 268 HIV infections;HIV infections 145;168 166;171 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. However, three CAB selections resulted in Q148R/K followed by secondary mutations conferring high-level cross-resistance to all INSTIs. 2018 Retrovirology Abstract HIV Q148K;Q148R 42;42 49;49 INSTI 128 134 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. One EVG-resistant variant (T66I) acquired L74M/G140S/S147G, L74M/E138K/S147G and H51Y with DTG CAB and BIC, respectively. 2018 Retrovirology Abstract HIV E138K;G140S;H51Y;L74M;L74M;S147G;S147G;T66I 65;47;81;42;60;53;71;27 70;52;85;46;64;58;76;31 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Similarly, most CAB selections (n = 18) resulted in R263K, S153Y, S147G, H51Y, or Q146L solitary mutations. 2018 Retrovirology Abstract HIV H51Y;Q146L;R263K;S147G;S153Y 73;82;52;66;59 77;87;57;71;64 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The development of Q148R/K with CAB can result in high-level cross-resistance to all INSTIs. 2018 Retrovirology Abstract HIV Q148K;Q148R 19;19 26;26 INSTI 85 91 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The E157Q substitution in integrase delayed the advent of resistance to INSTIs. 2018 Retrovirology Abstract HIV E157Q 4 9 INSTI;IN 72;26 78;35 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Two EVG-resistant variants developed resistance to DTG, BIC and CAB through the additional acquisition of E138A/Q148R and S230N, respectively. 2018 Retrovirology Abstract HIV E138A;Q148R;S230N 106;112;122 111;117;127 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. With DTG and BIC, solitary R263K (n = 27), S153F/Y (n = 7) H51Y (n = 2), Q146 R (n = 3) or S147G (n = 1) mutations conferred low-level (< 3-fold) resistance at weeks 36-46. 2018 Retrovirology Abstract HIV Q146R;R263K;S147G;S153F;S153Y 73;27;91;43;43 79;32;96;50;50 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. With EVG, T66I/A, E92G/V/Q, T97A or R263K (n = 16, 3, 2 and 1, respectively) arose by weeks 8-16, followed by 1-4 accessory mutations, conferring high-level resistance (> 100-fold) by week 36. 2018 Retrovirology Abstract HIV E92G;E92Q;E92V;R263K;T66A;T66I;T97A 18;18;18;36;10;10;28 26;26;26;41;16;16;32 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. A single Y86F mutation disrupts SERINC5 and tetherin antagonism but not CXCR4 down-modulation by SIVcol Nef, while mutation of a C-proximal di-leucine motif has the opposite effect. 2018 PLoS pathogens Abstract HIV Y86F 9 13 Nef 104 107 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Unexpectedly, the Y86F change in SIVcol Nef had little if any effect on viral replication and CD4+ T cell depletion in preactivated human CD4+ T cells and in ex vivo infected lymphoid tissue. 2018 PLoS pathogens Abstract HIV Y86F 18 22 Nef 40 43 30137335 Ultra-deep sequencing improves the detection of drug resistance in cellular DNA from HIV-infected patients on ART with suppressed viraemia. However, the detection of RAMs by UDS with a 1% cut-off was significantly higher than that of bulk sequencing for RT codons D67N (65.4% versus 52.3%), M184V (66.2% versus 52.3%), L210W (48.9% versus 36.4%) and T215Y (57.9% versus 42.1%) and PR codons M46I (46% versus 26%), I54L (12.4% versus 3.9%), V82A (44.5% versus 29.9%) and L90M (57.7% versus 42.5%). 2018 The Journal of antimicrobial chemotherapy Abstract HIV D67N;I54L;L210W;L90M;M184V;M46I;T215Y;V82A 124;274;179;330;151;251;210;300 128;278;184;334;156;255;215;304 PR;RT 241;114 243;116 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Here, we report that EFdA and NRTIs with a 4'-ethynyl- or 4'-cyano-moiety exerted activity against HIV-1 with an M184V mutation and multiple NRTI-resistant HIV-1s, whereas NRTIs with other moieties (e.g., 4'-methyl) did not show this activity. 2018 Cell chemical biology Abstract HIV M184V 113 118 NRTI;NRTI;NRTI 30;141;172 35;145;177 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Such interactions were maintained even in the presence of a broad resistance-endowing M184V substitution, thus potently inhibiting drug-resistant HIV-1 strains. 2018 Cell chemical biology Abstract HIV M184V 86 91 30189786 Substituting Generic Lamivudine for Emtricitabine in Virologically Suppressed HIV-Infected Patients. The two groups also showed similar values for CD4 counts, compliance, discontinuation, and M184V mutation; however, a slightly greater proportion of lamivudine patients experienced respiratory symptoms. 2018 Journal of correctional health care Abstract HIV M184V 91 96 30219320 Genome-scale analysis of evolutionary rate and selection in a fast-expanding Spanish cluster of HIV-1 subtype F1. We also found one substitution in Nef (H89F) that was specific to the cluster and experienced positive selection. 2018 Infection, genetics and evolution Abstract HIV H89F 39 43 Nef 34 37 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The most common NRTI mutation found was M184 V; K103 N and A98G were the most common NNRTI mutations seen. 2018 Virology journal Abstract HIV A98G;K103N;M184V 59;48;40 63;54;46 NNRTI;NRTI 85;16 90;20 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Thymidine Analogue Mutations (TAMs) such as M41 L, K70R and T215Y were found in all the groups; the most common of the TAMs found were M41 L and T215Y. 2018 Virology journal Abstract HIV K70R;M41L;M41L;T215Y;T215Y 51;44;135;60;145 55;49;140;65;150 30229661 Integrase Strand Transfer Inhibitor Resistance Mutations in Antiretroviral Therapy-Naive and Treatment-Experienced HIV Patients in South Korea. In the former group, both major INSTI resistance cases involved the nonpolymorphic E92Q mutation in the integrase strand. 2019 AIDS research and human retroviruses Abstract HIV E92Q 83 87 IN;INSTI 104;32 113;37 30229676 Short Communication: An Insertion of Seven Amino Acids in the Envelope Cytoplasmic Tail of HIV-2 Selected During Disease Progression Enhances Viral Replication. Using a molecular clone of the HIV-2ROD reference strain, site-directed mutagenesis experiments allowed the generation of plasmids with the insertion L791TAI or L791QRALTAI in the Env protein. 2019 AIDS research and human retroviruses Abstract HIV L791A;L791A;L791I;L791I;L791L;L791Q;L791R;L791T;L791T 150;161;150;161;161;161;161;150;161 157;172;157;172;172;172;172;157;172 Env 180 183 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. However, the accumulation of an Y135F mutation in NefYF9 out of the 4 epitopes, which is selected by HLA-A*24:02-restricted T cells, affected the ability of YF9-specific T cells to suppress HIV-1 replication. 2018 EBioMedicine Abstract HIV Y135F 32 37 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. INTERPRETATION: These findings indicate that the Y135F mutation is a key factor underlying the detrimental effect of HLA-B*35:01 on disease outcomes in HIV-1 clade B-infected individuals. 2018 EBioMedicine Abstract HIV Y135F 49 54 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. YF9-specific T cells failed to suppress replication of the Y135F mutant in vitro. 2018 EBioMedicine Abstract HIV Y135F 59 64 30277466 A comparison between two dolutegravir-based two-drug regimens as switch strategies in a multicentre cohort of HIV-1-infected patients. In the RPV group, during 371.0 PYFU, there were 5 VF (1 developed non-nucleoside reverse transcriptase inhibitor mutations Y181C and E138Q) and 13 TD. 2019 Antiviral therapy Abstract HIV E138Q;Y181C 133;123 138;128 NNRTI 66 102 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. While mutations G190A and E138A were concurrently found in both compartments, others such as G73S on PR and A62V, M184I, M230I on RT were identified in proviral DNA only. 2018 PloS one Abstract HIV A62V;E138A;G190A;G73S;M184I;M230I 108;26;16;93;114;121 112;31;21;97;119;126 PR;RT 101;130 103;132 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Four HIV-1 protease (PR) inhibitors, clinical inhibitors lopinavir and tipranavir, and two investigational compounds 4 and 5, were studied for their effect on the structure and activity of PR with drug-resistant mutation L76V (PRL76V). 2018 ACS omega Abstract HIV L76V 221 225 PR;PR;PR;PR 11;21;189;227 19;23;191;229 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. One cluster was associated with the G190A mutation and showed onward transmissions at high rate. 2018 PloS one Abstract HIV G190A 36 41 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. Viral subtype B was the most common (81.3%) as well as M184 V/I (85.3%) and K103 codon mutations (65.8%). 2018 BMC infectious diseases Abstract HIV M184I;M184V 55;55 63;63 30325769 The effect of primary drug resistance on CD4+ cell decline and the viral load set-point in HIV-positive individuals before the start of antiretroviral therapy. However, transmitted nucleoside reverse transcriptase inhibitor and protease inhibitor resistance appeared to be weakly associated with lower viral load set points, as were the polymorphic G16E or Q92K protease mutations. 2019 AIDS (London, England) Abstract HIV G16E;Q92K 189;197 193;201 NRTI;PR;PR 21;68;202 53;76;210 30325775 Sexual intermingling of Arab and Jewish MSM in Israel: results of a molecular epidemiology study. Overall, 13.1% (66/502) had TDRM; reverse transcriptase-K103N/S, M184 V, T215S and protease-L90M were the most common. 2019 AIDS (London, England) Abstract HIV K103N;K103S;L90M;M184V;T215S 42;42;83;65;73 63;63;96;71;78 PR;RT 83;34 91;55 30325775 Sexual intermingling of Arab and Jewish MSM in Israel: results of a molecular epidemiology study. Phylogenetic analysis demonstrated AMSM and JMSM clusters including L90M, K103N/S or T215S TDRM. 2019 AIDS (London, England) Abstract HIV K103N;K103S;L90M;T215S 74;74;68;85 81;81;72;90 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Propagation of the P122A and I124A mutants in T-cell lines led to the selection of compensatory mutations within CA. 2018 mBio Abstract HIV I124A;P122A 29;19 34;24 Capsid 113 115 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Transmission electron microscopy and cryo-electron tomography demonstrated that the P122A and I124A mutations induce severe structural defects in the immature Gag lattice and abrogate conical core formation. 2018 mBio Abstract HIV I124A;P122A 94;84 99;89 Gag 159 162 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. While mutations P123A and P125A were relatively well tolerated, mutation of P122 and I124 significantly impaired virus release, caused Gag processing defects, and abolished infectivity. 2018 mBio Abstract HIV P123A;P125A 16;26 21;31 Gag 135 138 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. X-ray crystallography indicated that the P122A and I124A mutations induce subtle changes in the structure of the mature CA lattice which were permissive for in vitro assembly of CA tubes. 2018 mBio Abstract HIV I124A;P122A 51;41 56;46 30346745 Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. Importantly, the boronic acid maintains its hydrogen bonds and its affinity for the drug-resistant D30N variant of HIV-1 protease. 2018 Journal of the American Chemical Society Abstract HIV D30N 99 103 PR 121 129 30364958 Compromise of Second-Line Antiretroviral Therapy Due to High Rates of Human Immunodeficiency Virus Drug Resistance in Mozambican Treatment-Experienced Children With Virologic Failure. M184V and Y181C were the most common mutations. 2020 Journal of the Pediatric Infectious Diseases Society Abstract HIV Y181C;M184V 10;0 15;5 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. Four carried mutations exclusively linked to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (K103N, K103N/S) and one carried mutations to both NNRTIs (G190S, K101E) and nucleoside reverse transcriptase inhibitors (NRTIs) (M184V). 2018 PloS one Abstract HIV G190S;K101E;K103N;K103N;K103S;M184V 161;168;110;103;110;232 166;173;117;108;117;237 NNRTI;NNRTI;NNRTI;NRTI;NRTI 94;153;45;224;179 100;159;81;229;211 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. NGS detection of variants at the 5% level increased detection of K65R in both naive and treated groups. 2019 The Journal of antimicrobial chemotherapy Abstract HIV K65R 65 69 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. One of 607 integrase sequences carried a DRM20% (Q148R). 2019 The Journal of antimicrobial chemotherapy Abstract HIV Q148R 49 54 IN 11 20 30381490 Dolutegravir Monotherapy of Simian Immunodeficiency Virus-Infected Macaques Selects for Several Patterns of Resistance Mutations with Variable Virological Outcomes. Some mutations, such as G118R, previously shown to severely impair the replication capacity in vitro, were associated with more sustained virological and immunological benefits of continued DTG therapy, while other mutations, such as E92Q and G140A/Q148K, were associated with more variable outcomes. 2019 Journal of virology Abstract HIV E92Q;G118R;G140A;Q148K 234;24;243;249 238;29;248;254 30381875 Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors by exploring the structure-activity relationship of solvent-exposed regions I. Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV-1. 2019 Chemical biology & drug design Abstract HIV E138K;K103N 49;39 54;44 30391482 In vitro evaluation of novel reverse transcriptase inhibitors TAF (tenofovir alafenamide) and OBP-601 (2,3-didehydro-3-deoxy-4-ethynylthymidine) against multi-drug resistant primary isolates of HIV-2. With one exception, all resistant viruses had canonical nucleoside reverse transcriptase inhibitors (NRTIs)-associated resistance mutations (K65R, N69S, V111I, Y115F, Q151M and M184V). 2019 Antiviral research Abstract HIV K65R;M184V;N69S;Q151M;V111I;Y115F 141;177;147;167;153;160 145;182;151;172;158;165 NRTI;NRTI 56;101 88;106 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. In contrast, resistances to non-NRTIs (NNRTI, 4.7%) doubled between 2014 and 2016 from 3.2% to 6.4% (ptrend = 0.02) mainly due to the K103N mutation (from 1.7% to 4.1%; ptrend = 0.03) predominantly detected in recently infected German MSM not linked to transmission clusters. 2018 PloS one Abstract HIV K103N 134 139 NNRTI;NNRTI 28;39 37;44 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Reduced susceptibility to recommended first-line therapies was low with 1.0% for PIs, 1.3% for NRTIs and 0.7% for INSTIs, but high for the NNRTIs efavirence (4.9%) and rilpivirine (6.0%) due to the K103N mutation and the polymorphic mutation E138A. 2018 PloS one Abstract HIV E138A;K103N 242;198 247;203 INSTI;NNRTI;NRTI;PI 114;139;95;81 120;145;100;84 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Transmitted INSTI mutations were present in only one case (T66I) and resistance to dolutegravir was not identified at all. 2018 PloS one Abstract HIV T66I 59 63 INSTI 12 17 30409215 Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay. George's, mainly M46I/L and I50 V (associated with PIs), D67 N, K65R, L74I, M184 V/I, and K219Q (NRTIs), and L100I (NNRTIs). 2018 AIDS research and therapy Abstract HIV D67N;I50V;K219Q;K65R;L100I;L74I;M184I;M184V;M46I;M46L 57;28;90;64;109;70;76;76;17;17 62;33;95;68;114;74;84;84;23;23 NNRTI;NRTI;PI 116;97;51 122;102;54 30430843 Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa. The most prevalent SDRMs were K103NS (7.5%), M184VI (2.4%), and V106AM (1.4%). 2019 AIDS research and human retroviruses Abstract HIV K103N;K103S;M184I;M184V;V106A;V106M 30;30;45;45;64;64 36;36;51;51;70;70 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. After switching to second-line ART, nine patients newly acquired the NRTI drug-resistant mutation, M184 V/I. 2018 BMC infectious diseases Abstract HIV M184I;M184V 99;99 107;107 NRTI 69 73 30445408 Torsional flexibility of undecorated catechol diether compound as potent NNRTI targeting HIV-1 reverse transcriptase. In this study, torsional flexibility of an undecorated catechol diether compound in the binding pocket of wild type and mutants (Y181C and K103N/Y181C) HIV-1 RT is investigated by using QM/MM calculations. 2019 Journal of molecular graphics & modelling Abstract HIV K103N;Y181C;Y181C 139;145;129 144;150;135 RT 158 160 30461149 Prevalence and determinants of resistance mutations in HIV-1-infected patients exposed to integrase inhibitors in a large Italian cohort. Overall, the Q148H/K/R plus G140A/C/S and/or E138A/K/T pattern, defining an intermediate level of resistance to DTG, was detected in 70 (15%) cases. 2019 HIV medicine Abstract HIV E138A;E138K;E138T;G140A;G140C;G140S;Q148H;Q148K;Q148R 45;45;45;28;28;28;13;13;13 54;54;54;37;37;37;22;22;22 30461149 Prevalence and determinants of resistance mutations in HIV-1-infected patients exposed to integrase inhibitors in a large Italian cohort. The most frequent INSTI resistance mutation was N155H, followed by Q148H/K/R, G140A/C/S, E138A/K/T and Y143C/H/R. 2019 HIV medicine Abstract HIV E138A;E138K;E138T;G140A;G140C;G140S;N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 89;89;89;78;78;78;48;67;67;67;103;103;103 98;98;98;87;87;87;53;76;76;76;112;112;112 INSTI 18 23 30461149 Prevalence and determinants of resistance mutations in HIV-1-infected patients exposed to integrase inhibitors in a large Italian cohort. Y143R and E138A were more prevalent in viral subtype B versus non-B [5.2 versus 1.5%, respectively (P = 0.04), and 3.1 versus 0%, respectively (P = 0.02)]. 2019 HIV medicine Abstract HIV E138A;Y143R 10;0 15;5 30462235 The HIV-1 reverse transcriptase E138A natural polymorphism decreases the genetic barrier to resistance to etravirine in vitro. CONCLUSIONS: E138A can contribute to reduced response to etravirine through a decreased genetic barrier to resistance. 2019 The Journal of antimicrobial chemotherapy Abstract HIV E138A 13 18 30462235 The HIV-1 reverse transcriptase E138A natural polymorphism decreases the genetic barrier to resistance to etravirine in vitro. However, the interpretation of E138A on etravirine susceptibility is not consistent across different genotypic resistance algorithms. 2019 The Journal of antimicrobial chemotherapy Abstract HIV E138A 31 36 30462235 The HIV-1 reverse transcriptase E138A natural polymorphism decreases the genetic barrier to resistance to etravirine in vitro. OBJECTIVES: The HIV-1 reverse transcriptase (RT) natural polymorphism E138A is included among the mutations with a minor impact on response to etravirine. 2019 The Journal of antimicrobial chemotherapy Abstract HIV E138A 70 75 RT;RT 22;45 43;47 30462235 The HIV-1 reverse transcriptase E138A natural polymorphism decreases the genetic barrier to resistance to etravirine in vitro. The aim of the study was to investigate the effect of E138A on the genetic barrier to resistance to etravirine in vitro. 2019 The Journal of antimicrobial chemotherapy Abstract HIV E138A 54 59 30476106 Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients. Overall, the presence of at least one doravirine resistance-associated mutation (n = 137; 1.4%) or the K103N/Y181C mutations (n = 5; 0.05%) was very rare. 2019 The Journal of antimicrobial chemotherapy Abstract HIV K103N;Y181C 103;109 108;114 30476106 Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients. The most prevalent mutations were V108I (n = 62; 0.6%), Y188L (n = 18; 0.2%), H221Y (n = 18; 0.2%) and Y318F (n = 23; 0.2%). 2019 The Journal of antimicrobial chemotherapy Abstract HIV H221Y;V108I;Y188L;Y318F 78;34;56;103 83;39;61;108 30476106 Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients. We studied the prevalence of doravirine resistance-associated mutations previously identified in vitro: V106A/M, V108I, Y188L, V190S, H221Y, F227C/L/V, M230I/L, L234I, P236L, Y318F and K103N/Y181C. 2019 The Journal of antimicrobial chemotherapy Abstract HIV F227C;F227L;F227V;H221Y;K103N;L234I;M230I;M230L;P236L;V106A;V106M;V108I;V190S;Y181C;Y188L;Y318F 141;141;141;134;185;161;152;152;168;104;104;113;127;191;120;175 150;150;150;139;190;166;159;159;173;111;111;118;132;196;125;180 30476165 Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL). Neither M184V nor integrase resistance mutations were detected after failure or blips. 2019 The Journal of antimicrobial chemotherapy Abstract HIV M184V 8 13 IN 18 27 30477526 Long-term virological outcome in children receiving first-line antiretroviral therapy. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%-K103N and Y181C being the major NNRTI mutations-observed. 2018 AIDS research and therapy Abstract HIV K103N;Y181C 89;99 94;104 NNRTI;NNRTI 43;121 48;126 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. The HIV genotype revealed Met184Val, Leu74Val, Leu100Ile, and Lys103Asn mutations in reverse transcriptase, and the phenotype showed susceptibility to tenofovir disoproxil fumarate and resistance to emtricitabine. 2018 The lancet. HIV Abstract HIV K103N;L100I;L74V;M184V 62;47;37;26 71;56;45;35 RT 85 106 30506751 An in silico pharmacological approach toward the discovery of potent inhibitors to combat drug resistance HIV-1 protease variants. Herein, we strive for compounds that can stifle the function of wild-type (WT) HIV-1 PR along with four major single mutants (I54M, V82T, I84V, and L90M) instigating resistance to the PIs using in silico approach. 2019 Journal of cellular biochemistry Abstract HIV I54M;I84V;L90M;V82T 126;138;148;132 130;142;152;136 PI;PR 184;85 187;87 30513108 Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). 2018 PLoS medicine Abstract HIV K101E;K101P;K219E;K219Q;P225H 169;169;76;76;192 176;176;83;83;197 NNRTI;NNRTI;NRTI;NRTI 152;104;61;17 157;140;65;49 30521379 Blocking Tyr265 nitration of protein phosphatase 2A attenuates nitrosative stress-induced endothelial dysfunction in renal microvessels. To devise an endothelial-targeted anti-PP2Ac nitration strategy, a mimic peptide, tyrosine 265 wild type (Y265WT), conjugated with the cell-penetrating peptide HIV-1 TAT protein (TAT) was synthesized. 2019 FASEB journal Abstract HIV Y265T;Y265W 106;106 112;112 Tat;Tat 166;179 169;182 30525601 Effect of alpha-Methoxy Substitution on the Anti-HIV Activity of Dihydropyrimidin-4(3 H)-ones. The various alpha-methoxy DABO series (12-14) present different SAR at the dihalo benzyl substitution, with the most potent compounds (12d,e and 13c) showing similar (picomolar/nanomolar) anti-HIV-1 potency as the corresponding alpha-methyl analogues against wt HIV-1, and 10-100-fold increased potency (up to low nanomolar) against clinically relevant K103N, Y181C, Y188L, IRLL98, and K103N+Y181C HIV-1 mutant strains, highlighting the importance of the alpha-methoxy substitution to provide highly efficient DABOs as "second generation" NNRTIs. 2019 Journal of medicinal chemistry Abstract HIV K103N;K103N;Y181C;Y181C;Y188L 353;386;360;392;367 358;391;365;397;372 NNRTI 539 545 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Considerable losses of potency were observed against protease variants with I84V and I50V mutations for all three inhibitors. 2019 ACS infectious diseases Abstract HIV I50V;I84V 85;76 89;80 PR 53 61 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The crystal structures revealed an unexpected conformational change in the flap region of I50V protease bound to the analogue with the largest P1' moiety, indicating interdependency between the S1' subsite and the flap region. 2019 ACS infectious diseases Abstract HIV I50V 90 94 PR 95 103 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). 2019 The Journal of antimicrobial chemotherapy Abstract HIV T215F;T215Y 78;69 83;74 30557314 The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. The furin cleavage site of the Env protein was replaced with a flexible linker and an I559P mutation introduced. 2018 PloS one Abstract HIV I559P 86 91 Env 31 34 30560685 Pretreatment HIV Drug Resistance and Virologic Outcomes to First-Line Antiretroviral Therapy in Peru. Blood specimens from ARV-naive individuals were assessed for PDR to NNRTI-based ART by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant within an individual's HIV quasispecies at reverse transcriptase codons M41L, K65R, K103N, Y181C, M184V, and G190A, and by Sanger consensus sequencing (CS). 2019 AIDS research and human retroviruses Abstract HIV G190A;K103N;K65R;M184V;M41L;Y181C 259;234;228;248;222;241 264;239;232;253;226;246 RT;NNRTI 193;68 214;73 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. The most prevalent TDR mutation was K103N (n = 5), with sequences forming transmission clusters of two and three taxa each. 2018 PloS one Abstract HIV K103N 36 41 30567982 Resistance to Second-Generation HIV-1 Maturation Inhibitors. In selection experiments with subtype C HIV-1, we identified mutations at CA residue 230 (CA-V230M) and SP1 residue 1 (SP1-A1V), residue 5 (SP1-S5N), and residue 10 (SP1-G10R). 2019 Journal of virology Abstract HIV A1V;V230M;G10R;S5N 123;93;170;144 126;98;174;147 SP1;SP1;SP1;SP1;Capsid;Capsid 104;119;140;166;74;90 107;122;143;169;76;92 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Here we report >10-fold increase in dolutegravir resistance after the single addition of T97A in 2 individuals with prior INSTI resistance receiving dolutegravir salvage therapy. 2018 Open forum infectious diseases Abstract HIV T97A 89 93 INSTI 122 127 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. HIV integrase mutation T97A emerges after suboptimal therapy with integrase strand transfer inhibitors (INSTIs), but the contribution of T97A to dolutegravir resistance remains uncertain. 2018 Open forum infectious diseases Abstract HIV T97A;T97A 23;137 27;141 INSTI;IN;IN 104;4;66 110;13;75 30569276 Prevalence of HIV-1 transmitted drug resistance and viral suppression among recently diagnosed adults in Sao Paulo, Brazil. One or more TDR (based on the WHO surveillance list) was observed in 10.9% (CI 95%, 8.6-13.6) of the sequences, the most common of which was the K103 N mutation, which confers resistance to first-generation drugs of the non-nucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral drug class. 2019 Archives of virology Abstract HIV K103N 145 151 NNRTI;NNRTI 220;268 256;273 30573649 Double trouble? Gag in conjunction with double insert in HIV protease contributes to reduced DRV susceptibility. An in vitro phenotypic assay showed the L38 N L protease to be susceptible to lopinavir (LPV), atazanavir (ATV) and darunavir in the context of an unrelated Gag. 2019 The Biochemical journal Abstract HIV L38N 40 45 PR;Gag 48;157 56;160 30573649 Double trouble? Gag in conjunction with double insert in HIV protease contributes to reduced DRV susceptibility. However, in the presence of the related Gag, L38 N L showed reduced susceptibility to darunavir while remaining susceptible to LPV and ATV. 2019 The Biochemical journal Abstract HIV L38N 45 50 Gag 40 43 30573649 Double trouble? Gag in conjunction with double insert in HIV protease contributes to reduced DRV susceptibility. Isothermal titration calorimetry showed that 10% less of L38 N L protease was in the active conformation as compared with a reference strain. 2019 The Biochemical journal Abstract HIV L38N 57 62 PR 65 73 30573649 Double trouble? Gag in conjunction with double insert in HIV protease contributes to reduced DRV susceptibility. L38 N L protease displayed a +-50% reduction in K M and k cat The catalytic efficiency (k cat/K M) of L38 N L protease was not significantly different from that of wild type although there was a 42% reduction in specific activity for the variant. 2019 The Biochemical journal Abstract HIV L38N;L38N 0;102 5;107 PR;PR 8;110 16;118 30573649 Double trouble? Gag in conjunction with double insert in HIV protease contributes to reduced DRV susceptibility. We have identified an unusual HIV-1 subtype C variant that contains insertions of leucine and asparagine (L38 N L) in the hinge region of protease at position 38. 2019 The Biochemical journal Abstract HIV L38N 106 112 PR 138 146 30606670 Design, synthesis and biological evaluation of novel acetamide-substituted doravirine and its prodrugs as potent HIV-1 NNRTIs. Besides, 8i and 8k shown moderate activity against the double RT mutant (K103N + Y181C) HIV-1 RES056 strain. 2019 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 73;81 79;86 RT 62 64 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. Furthermore, L10 V/F/I (6.82%), A71V (4.55%), and I54V (4.55%) mutations were common in protease inhibitors (PIs). 2019 Virology journal Abstract HIV A71V;I54V;L10F;L10I;L10V 32;50;13;13;13 36;54;22;22;22 PI;PR 109;88 112;96 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. M184 V/I (26.14%), T69S (11.36%), and T215Y/I (10.23%) mutations were the most common in nucleoside reverse transcriptase inhibitors (NRTIs), and K103 N/R/S (21.59%), V179D/E (20.45%) in Non-NRTIs (NNRTIs). 2019 Virology journal Abstract HIV K103N;K103R;K103S;M184I;M184V;T215I;T215Y;T69S;V179D;V179E 146;146;146;0;0;38;38;19;167;167 156;156;156;8;8;45;45;23;174;174 NNRTI;NRTI;NNRTI;NRTI 198;134;187;89 204;139;196;121 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Meanwhile, both compounds exhibited comparable activities with ETV toward the virus with double mutations F227L+V106A and K103N+Y181C. 2019 Journal of medicinal chemistry Abstract HIV F227L;K103N;V106A;Y181C 106;122;112;128 111;127;117;133 30640198 High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014. The most frequent mutations were K103N/S (48.0%), M184V (37.5%), G190A/S (15.1%), and Y181C/G/V (14.1%). 2019 The Pediatric infectious disease journal Abstract HIV G190A;G190S;K103N;K103S;M184V;Y181C;Y181G;Y181V 65;65;33;33;50;86;86;86 72;72;40;40;55;95;95;95 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. The integrase mutation R263K has been observed in tissue culture experiments and in patients treated with dolutegravir monotherapy in clinical trials. 2019 Open forum infectious diseases Abstract HIV R263K 23 28 IN 4 13 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. We describe the first report of the R263K integrase mutation in a dolutegravir-exposed subtype D-infected individual with vertically acquired HIV. 2019 Open forum infectious diseases Abstract HIV R263K 36 41 IN 42 51 30648556 Active-site deformation in the structure of HIV-1 RT with HBV-associated septuple amino acid substitutions rationalizes the differential susceptibility of HIV-1 and HBV against 4'-modified nucleoside RT inhibitors. The most active RT mutant, HIV-1 RT7MC, carrying Q151M/G112S/D113A/Y115F/F116Y/F160L/I159L was successfully crystallized, and its three-dimensional structure was determined in complex with DNA:dGTP/entecavir-triphosphate (ETV-TP), a potent anti-HBV guanosine analogue RT inhibitor, at a resolution of 2.43 A and 2.60 A, respectively. 2019 Biochemical and biophysical research communications Abstract HIV F116Y;F160L;G112S;Q151M;Y115F 73;79;55;49;67 78;84;60;54;72 RT;RT;RT 16;33;268 18;35;270 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The longest mean survival times were calculated for the NNRTI mutations K103N (5.3 years, 95% CI 4.2-5.6) and E138A/G/K (8.0 years, 95% CI 5.8-10.2 / 7.9 years, 95% CI 5.4-10.3 / 6.7 years, 95% CI 6.7-6.7) and for the NRTI mutation M41L (6.4 years, 95% CI 6.0-6.7).The long persistence of single TDRMs indicates that onward transmission from ART-naive individuals is the main cause for TDR in Germany. 2019 PloS one Abstract HIV E138A;E138G;E138K;K103N;M41L 110;110;110;72;232 119;119;119;77;236 NNRTI;NRTI 56;218 61;222 30651369 The Polar Region of the HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing the gp120-gp41 Association. Furthermore, S532A mutation significantly reduced HIV-1 infectivity and fusogenicity but not Env expression and cleavage. 2019 Journal of virology Abstract HIV S532A 13 18 Env 93 96 30651369 The Polar Region of the HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing the gp120-gp41 Association. Three PR mutations containing S532P substantially reduced gp120 and gp41 association, Env trimer stability, and increased gp120 shedding. 2019 Journal of virology Abstract HIV S532P 30 35 gp120;gp120;gp41;Env;PR 58;122;68;86;6 63;127;72;89;8 30651369 The Polar Region of the HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing the gp120-gp41 Association. Through analyzing the PR sequences of 57,645 HIV-1 isolates, we performed targeted mutagenesis and functional studies of three highly conserved polar residues in the PR (S532P, T534A, and T536A) which have not been characterized previously. 2019 Journal of virology Abstract HIV S532P;T534A;T536A 170;177;188 175;182;193 PR;PR 22;166 24;168 30668734 Detection of pretreatment minority HIV-1 reverse transcriptase inhibitor-resistant variants by ultra-deep sequencing has a limited impact on virological outcomes. The RNA MDRVs corresponded to DNA MDRVs, except for M100I and Y188H. 2019 The Journal of antimicrobial chemotherapy Abstract HIV M100I;Y188H 52;62 57;67 30695102 Viral evolution in the cell-associated HIV-1 DNA during early ART can lead to drug resistance and virological failure in children. Among the nonresponders carrying a resistant virus (86.6%) at virological failure, 26% harbored clinically relevant low-frequency DRMs in the cell-associated DNA at month six (0.5%-20%; K103N, G190A, Y181C, and M184I). 2019 Journal of medical virology Abstract HIV G190A;K103N;M184I;Y181C 193;186;211;200 198;191;216;205 30714528 Molecular Antiretroviral Resistance Markers of Human Immunodeficiency Virus-1 of CRF01_AE Subtype in Bali, Indonesia. Molecular marker mutations, which were found in more than 50% of treatment failure patients, were M184V (100%), T215A/Y/F (88.2%), D67N/G (76.5%), and M41L (58.8%). 2018 Current HIV research Abstract HIV D67G;D67N;M184V;M41L;T215A;T215F;T215Y 131;131;98;151;112;112;112 137;137;103;155;121;121;121 30721060 Exploiting the Tolerant Region I of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Binding Pocket: Discovery of Potent Diarylpyrimidine-Typed HIV-1 NNRTIs against Wild-Type and E138K Mutant Virus with Significantly Improved Water Solubility and Favorable Safety Profiles. Diarylpyrimidine derivatives (DAPYs) exhibit robust anti-HIV-1 potency, although they have been compromised by E138K variant and severe side-effects and been suffering from poor water solubility. 2019 Journal of medicinal chemistry Abstract HIV E138K 111 116 30721060 Exploiting the Tolerant Region I of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Binding Pocket: Discovery of Potent Diarylpyrimidine-Typed HIV-1 NNRTIs against Wild-Type and E138K Mutant Virus with Significantly Improved Water Solubility and Favorable Safety Profiles. The anti-HIV-1 activities of 11c (EC50(WT) = 0.0035 muM, EC50(E138K) = 0.0075 muM) were the same as and 2-fold better than that of the lead etravirine against the wild-type and E138K mutant HIV-1, respectively, with a relative low cytotoxicity (CC50 >= 173 muM). 2019 Journal of medicinal chemistry Abstract HIV E138K;E138K 177;62 182;67 30732150 Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana. HIV-2 drug resistance mutations (M184V, K65R, Y115F) were identified in 1 patient.This study is the first to report HIV-2 viral load and drug resistance mutations in HIV-2 strains from Ghana. 2019 Medicine Abstract HIV K65R;M184V;Y115F 40;33;46 44;38;51 30738756 Mutational analysis of gyrB at amino acids: G481A & D505A in multidrug resistant (MDR) tuberculosis patients. All samples had mutations at Gly481Ala, whereas, 24 samples (45.28%) had mutations at Asp505Ala. 2019 Journal of infection and public health Abstract HIV D505A;G481A 86;29 95;38 Asp 86 89 30738756 Mutational analysis of gyrB at amino acids: G481A & D505A in multidrug resistant (MDR) tuberculosis patients. The 24 samples had mutation in gyrB gene out of 53 (45.28%), on both of positions of amino acids Gly481Ala and Asp505Ala. 2019 Journal of infection and public health Abstract HIV D505A;G481A 111;97 120;106 Asp 111 114 30738756 Mutational analysis of gyrB at amino acids: G481A & D505A in multidrug resistant (MDR) tuberculosis patients. We evaluated mutations in gyrB gene at amino acid positions G481A and D505A of M. 2019 Journal of infection and public health Abstract HIV D505A;G481A 70;60 75;65 30741163 Provincial and national prevalence estimates of transmitted HIV-1 drug resistance in South Africa measured using two WHO-recommended methods. Inclusion of all nine of South Africa's provinces in the 2012 survey enabled calculation of a national TDR point prevalence estimate: TDR to the NNRTI drug class was 5.4% (95% CI 3.7, 7.8%), with K103N and V106M being the most frequently detected mutations. 2019 Antiviral therapy Abstract HIV K103N;V106M 196;206 201;211 NNRTI 145 150 30744272 [Prevalence of antiretroviral drug resistance in treatment-naive injecting drug users infected with HIV-1 in Guangzhou, 2008-2015]. Higher rate of V179E mutation in the non-nucleoside reverse transcriptase region was detected in other subtypes and subtype CRF07_BC. 2019 Zhonghua liu xing bing xue za zhi Abstract HIV V179E 15 20 NNRTI 37 73 30744272 [Prevalence of antiretroviral drug resistance in treatment-naive injecting drug users infected with HIV-1 in Guangzhou, 2008-2015]. The highest mutation rate of E138A was detected in subtype CRF08_BC (3.23%). 2019 Zhonghua liu xing bing xue za zhi Abstract HIV E138A 29 34 30753573 Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). 2019 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Q148H;Q148R;R263K;Y143C;Y143G 57;68;68;97;81;81 62;75;75;102;88;88 INSTI 0 5 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. The envelope protein (Env) contained a flexible glycine linker and I559P mutation. 2019 Journal of virology Abstract HIV I559P 67 72 Env;Env 4;22 12;25 30768160 HIV-1 protease, Gag and gp41 baseline substitutions associated with virological response to a PI-based regimen. All were localized outside Gag cleavage sites (G62D, matrix; N315H, capsid; and Y441S, p1). 2019 The Journal of antimicrobial chemotherapy Abstract HIV G62D;N315H;Y441S 47;61;80 51;66;85 Capsid;Matrix;Gag 68;53;27 74;59;30 30768160 HIV-1 protease, Gag and gp41 baseline substitutions associated with virological response to a PI-based regimen. Among CRF02_AG sequences, I72M and E21D mutations were associated with VF (P = 0.03 for both). 2019 The Journal of antimicrobial chemotherapy Abstract HIV E21D;I72M 35;26 39;30 30768160 HIV-1 protease, Gag and gp41 baseline substitutions associated with virological response to a PI-based regimen. In Gag, mutations associated with VF were G62D, N315H and Y441S (P = 0.005, P = 0.007 and P = 0.0003, respectively). 2019 The Journal of antimicrobial chemotherapy Abstract HIV G62D;N315H;Y441S 42;48;58 46;53;63 Gag 3 6 30768160 HIV-1 protease, Gag and gp41 baseline substitutions associated with virological response to a PI-based regimen. In gp41, the I270T mutation, localized in the cytoplasmic tail, was associated with VF (P = 0.003), and the I4L mutation, in the fusion peptide, was associated with virological success (P = 0.004). 2019 The Journal of antimicrobial chemotherapy Abstract HIV I270T;I4L 13;108 18;111 gp41 3 7 30768160 HIV-1 protease, Gag and gp41 baseline substitutions associated with virological response to a PI-based regimen. Overall, T4A and S37T mutations in protease were identified as being associated with VF (P = 0.02 and P = 0.005, respectively). 2019 The Journal of antimicrobial chemotherapy Abstract HIV S37T;T4A 17;9 21;12 PR 35 43 30769200 Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. 2019 International journal of antimicrobial agents Abstract HIV F227L;G190E;L234I;M230L;V106A;V106A;V106M;V106M;Y188L 90;75;109;68;82;101;82;101;61 95;80;114;73;89;108;89;108;66 30769200 Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. 2019 International journal of antimicrobial agents Abstract HIV K103N;P225H;V106A;V106M;V108I;Y188C;Y188H 92;98;63;63;81;72;72 97;103;70;70;86;79;79 30769200 Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors. Moreover, EFV use (OR = 1.76, 95% CI 1.19-2.58) and ETR use (OR = 1.72, 95% CI 1.10-2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05-0.50). 2019 International journal of antimicrobial agents Abstract HIV Y188L 128 133 30769200 Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors. The most common DOR resistance mutation was Y188L. 2019 International journal of antimicrobial agents Abstract HIV Y188L 44 49 30783503 Aryl Substituted Benzimidazolones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors. A second generation benzimidazolone inhibitor (compound 42) not only showed inhibitory activity against wild-type HIV but also remained active against HIV containing the K103N, Y181C, and K103N/Y181C drug resistance mutations. 2019 ACS medicinal chemistry letters Abstract HIV K103N;K103N;Y181C;Y181C 170;188;194;177 175;193;199;182 30783503 Aryl Substituted Benzimidazolones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors. The first generation benzimidazolone inhibitors were found to be potent inhibitors of wild-type HIV reverse transcriptase but were ineffective in the presence of common resistance mutations such as K103N and Y181C. 2019 ACS medicinal chemistry letters Abstract HIV K103N;Y181C 198;208 203;213 RT 100 121 30788976 Synthesis and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors. Antiviral activities of 20 compounds were measured against wild type human immunodeficiency virus-1 and mutant reverse transcriptase strains (K103N, Y181C) using a cytoprotection assay. 2019 Antiviral chemistry & chemotherapy Abstract HIV K103N;Y181C 142;149 147;154 RT 111 132 30793915 Absence of Integrase Strand Transfer Inhibitor Associated Resistance in Antiretroviral Therapy Naive and Experienced Individuals from Western India. Other accessory mutations were L74IM (34.48%), Q95K (1.72%), and T97A (1.72%). 2019 AIDS research and human retroviruses Abstract HIV L74I;L74M;Q95K;T97A 31;31;47;65 36;36;51;69 30793915 Absence of Integrase Strand Transfer Inhibitor Associated Resistance in Antiretroviral Therapy Naive and Experienced Individuals from Western India. Overall there was absence of major INSTI resistance mutation, however, E157Q (13.79%) emerged as common polymorphic mutation. 2019 AIDS research and human retroviruses Abstract HIV E157Q 71 76 INSTI 35 40 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. Both cases resulted in rise in HIV RNA levels and emergence of M184 V mutation and resistance to elvitegravir and raltegravir. 2019 Journal of the International Association of Providers of AIDS Care Abstract HIV M184V 63 69 30799830 Resistance profile of children and adolescents infected with HIV-1 in urban areas in Togo. The mutations associated with the most frequent NRTIs were M184V, Y181C, and T215Y. 2018 Medecine et sante tropicales Abstract HIV M184V;T215Y;Y181C 59;77;66 64;82;71 NRTI 48 53 30803972 Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants. HIV-2 integrase mutants G140S/Q148R and G140S/Q148H were 34- and 110-fold resistant to bictegravir, respectively; other resistance-associated mutations conferred <=5-fold changes in bictegravir susceptibility. 2019 Antimicrobial agents and chemotherapy Abstract HIV G140S;G140S;Q148H;Q148R 24;40;46;30 29;45;51;35 IN 6 15 30804369 Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation. Knock down of TRIM33 reverts the phenotype of an HIV-1 molecular clone carrying substitution of IN serine 57 to alanine, a mutation known to impair viral DNA integration. 2019 Nature communications Abstract HIV S57A 99 119 IN 96 98 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Competitive fitness experiments indicated that the V142I Vif and LEF-1 binding site mutations created a virus that is better adapted to growing in the presence of A3G than the wild-type virus.IMPORTANCE Although antiretroviral therapy can suppress HIV-1 replication effectively, virus reservoirs persist in infected individuals and virus replication rapidly rebounds if therapy is interrupted. 2019 mBio Abstract HIV V142I 51 56 Vif 57 60 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Here we show that resistance to these agents is dependent on an amino acid substitution in Vif (V142I) and on a point mutation that likely upregulates transcription by modifying the lymphocyte enhancing factor 1 (LEF-1) binding site. 2019 mBio Abstract HIV V142I 96 101 Vif 91 94 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. This docking site is lost when Vif acquires the V142I mutation that leads to inhibitor resistance. 2019 mBio Abstract HIV V142I 48 53 Vif 31 34 30814280 CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. Adaptation of N57A HIV-1LAI selected for a second CA mutation, G94D, which rescued the N57A infectivity defect in HIV-1LAI but not HIV-1NL4-3 The rescue of N57A by G94D in HIV-1LAI is abrogated by CsA treatment in some cell types, demonstrating that this rescue is CypA dependent. 2019 Journal of virology Abstract HIV G94D;G94D;N57A;N57A;N57A 63;164;14;87;156 67;168;18;91;160 Capsid 50 52 30814280 CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. Capsid permeabilization and reverse transcription are altered when N57A is incorporated into HIV-1NL4-3 but not HIV-1LAI The N57A infectivity defect is significantly exacerbated in both virus strains in the presence of cyclosporine (CsA), indicating that N57A infectivity is dependent upon CA interacting with host factor cyclophilin A (CypA). 2019 Journal of virology Abstract HIV N57A;N57A;N57A 67;125;255 71;129;259 RT;Capsid;Capsid 28;0;290 49;6;292 30814280 CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. Here, we show that the N57A mutation confers a postentry infectivity defect that significantly differs in magnitude between the common lab-adapted molecular clones HIV-1NL4-3 (>10-fold) and HIV-1LAI (2- to 5-fold) in multiple human cell lines and primary CD4+ T cells. 2019 Journal of virology Abstract HIV N57A 23 27 30814280 CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. The mutation N57A in the viral CA protein renders HIV-1 cell cycle dependent, allowing examination of HIV-1 infection of nondividing cells. 2019 Journal of virology Abstract HIV N57A 13 17 Capsid 31 33 30814280 CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. We have shown that two widely used HIV-1 molecular clones exhibit significantly different N57A infectivity phenotypes due to fewer than a handful of CA amino acid differences and that these clones are both represented in HIV-infected individuals. 2019 Journal of virology Abstract HIV N57A 90 94 Capsid 149 151 HIV infections 221 233 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Here, we report that in the globally dominant HIV-1 clade C, Tat displays a naturally occurring polymorphism, R57S, in its basic domain, which mediates cellular uptake. 2019 Scientific reports Abstract HIV R57S 110 114 Tat 61 64 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. In decapeptides corresponding to the basic domain, a R57S substitution caused up to a 70% reduction in uptake. 2019 Scientific reports Abstract HIV R57S 53 57 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. The R57S substitution dampened this response. 2019 Scientific reports Abstract HIV R57S 4 8 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Transactivation by Tat-B was significantly reduced by R57S substitution, while that of Tat-C was enhanced by the reciprocal S57R substitution. 2019 Scientific reports Abstract HIV R57S;S57R 54;124 58;128 Tat;Tat 19;87 22;90 30825471 Insight into the mechanism of action of EP-39, a bevirimat derivative that inhibits HIV-1 maturation. Finally, using NMR, we have shown that the interaction of EP-39 with a peptide carrying the SP1-A1V mutation (CA-SP1(A1V)-NC) is almost suppressed in comparison with the wild type peptide. 2019 Antiviral research Abstract HIV A1V;A1V 96;117 99;120 SP1;SP1;NC;Capsid 92;113;122;110 95;116;124;112 30825471 Insight into the mechanism of action of EP-39, a bevirimat derivative that inhibits HIV-1 maturation. We also identified six mutations that confer BVM resistance (CA-A194T, CA-L231F, CA-L231M, SP1-A1V, SP1-S5N and SP1-V7A). 2019 Antiviral research Abstract HIV A194T;A1V;L231F;L231M;S5N;V7A 64;95;74;84;104;116 69;98;79;89;107;119 SP1;SP1;SP1;Capsid;Capsid;Capsid 91;100;112;61;71;81 94;103;115;63;73;83 30825471 Insight into the mechanism of action of EP-39, a bevirimat derivative that inhibits HIV-1 maturation. We found that EP-39-resistant viruses have four mutations within the CA domain (CA-A194T, CA-T200N, CA-V230I, and CA-V230A) and one in the first residue of SP1 (SP1-A1V). 2019 Antiviral research Abstract HIV A194T;A1V;T200N;V230A;V230I 83;165;93;117;103 88;168;98;122;108 SP1;SP1;Capsid;Capsid;Capsid;Capsid;Capsid 156;161;69;80;90;100;114 159;164;71;82;92;102;116 30839042 Targeting the hydrophobic channel of NNIBP: discovery of novel 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs with high potency against wild-type and K103N mutant virus. Among them, meta-methylbenzoate (ZL2, EC50(IIIB) = 0.020 muM, EC50(K103N) = 0.043 muM, CC50 > 241.52 muM), para-methylbenzoate (ZL3, EC50(IIIB) = 0.013 muM, EC50 (K103N) = 0.022 muM, CC50 > 241.52 muM) and para-phenol (ZL7, EC50(IIIB) = 0.014 muM, EC50 (K103N) = 0.054 muM, CC50 = 2.1 muM) derivatives are the three most promising compounds which are superior to the first-line antiretroviral drug efavirenz (EC50(IIIB) = 0.003 muM, EC50 (K103N) = 0.11 muM, CC50 > 6.34 muM) against the K103N mutant strain. 2019 Organic & biomolecular chemistry Abstract HIV K103N;K103N;K103N;K103N;K103N 163;254;439;487;67 168;259;444;492;72 30839042 Targeting the hydrophobic channel of NNIBP: discovery of novel 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs with high potency against wild-type and K103N mutant virus. Interestingly, some compounds displayed remarkable potency in inhibiting K103N mutant virus, a key drug-resistant mutant to NNRTIs. 2019 Organic & biomolecular chemistry Abstract HIV K103N 73 78 NNRTI 124 130 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. [3H]WIN35,428 binding sites were not altered in Y88F/H547A but decreased in Y88F/K92M/H547A. 2019 Scientific reports Abstract HIV H547A;K92M;Y88F;H547A;Y88F 86;81;76;53;48 91;85;80;58;52 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Compared to wild-type hDAT, the Vmax values of [3H]Dopamine uptake were increased by 96% in Y88F/H547A but decreased by 97% in Y88F/K92M/H547A. 2019 Scientific reports Abstract HIV H547A;K92M;Y88F;H547A;Y88F 137;132;127;97;92 142;136;131;102;96 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. This study evaluated the effects of double (Y88F/H547A) and triple (Y88F/K92M/H547A) mutations on basal dopamine uptake, Tat-induced inhibition of DAT function, and dynamic transport process. 2019 Scientific reports Abstract HIV Y88F;H547A;K92M;Y88F;H547A 68;78;73;44;49 72;83;77;48;54 Tat 121 124 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. We have reported that single point mutations on human DAT (hDAT) at tyrosine88 (Y88F), lysine92 (K92M), and histidine547 (H547A) differentially regulate basal dopamine uptake but diminish Tat-induced inhibition of dopamine uptake by changing dopamine transport process. 2019 Scientific reports Abstract HIV H547A;K92M;Y88F 122;97;80 127;101;84 Tat 188 191 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Y88F/H547A displayed an attenuation of zinc-augmented [3H]WIN35,428 binding, increased basal dopamine efflux, and reduced amphetamine-induced dopamine efflux, indicating this mutant alters transporter conformational transitions. 2019 Scientific reports Abstract HIV H547A;Y88F 5;0 10;4 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Y88F/H547A mutant attenuated Tat-induced inhibition of dopamine uptake observed in wild-type hDAT. 2019 Scientific reports Abstract HIV H547A;Y88F 5;0 10;4 Tat 29 32 30859472 Polymorphisms in the APOBEC3G gene of Chinese rhesus macaques affect resistance to ubiquitination and degradation mediated by HIV-2 Vif. According to the predicted structure of the A3G protein, we predicted that the E88K and G212D mutations, both on the surface of the A3G protein, would have a significant effect on Vif-induced A3G degradation. 2019 Archives of virology Abstract HIV E88K;G212D 79;88 83;93 Vif 180 183 30859472 Polymorphisms in the APOBEC3G gene of Chinese rhesus macaques affect resistance to ubiquitination and degradation mediated by HIV-2 Vif. Unexpectedly, another polymorphism L71R, conferred resistance to Vif-mediated ubiquitin degradation, strongly suggesting that L71R might play an important role in antiviral defense mechanisms. 2019 Archives of virology Abstract HIV L71R;L71R 35;126 39;130 Vif 65 68 30861512 Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9-15 Months in 14 Triangular Clinics in Iran, 2015-2016. M184I/V mutation was the most frequent (31.6%) mutation among NRTI-based regimens. 2018 Intervirology Abstract HIV M184I;M184V 0;0 7;7 NRTI 62 66 30861512 Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9-15 Months in 14 Triangular Clinics in Iran, 2015-2016. Moreover, K103E/N was the most frequent (34.2%) NNRTI mutation. 2018 Intervirology Abstract HIV K103E;K103N 10;10 17;17 NNRTI 48 53 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. In an adjusted model including years since suppression, persistent proviral K103N was 2.6 times more likely (95% confidence interval, 1.0-6.4) per log10 higher human immunodeficiency virus RNA at EFV failure. 2019 Open forum infectious diseases Abstract HIV K103N 76 81 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Methods: Participants with virologic failure of EFV-based regimens and drug-resistant viremia with the K103N mutation in plasma ribonucleic acid (RNA) were identified from AIDS Clinical Trials Group (ACTG) studies A364 and A5095. 2019 Open forum infectious diseases Abstract HIV K103N 103 108 AIDS 172 176 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Sanger sequencing of proviral DNA detected K103N as well as additional reverse-transcriptase inhibitor (RTI) mutations. 2019 Open forum infectious diseases Abstract HIV K103N 43 48 RT;RT 71;104 92;107 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Ultradeep sequencing confirmed persistence of K103N in 71% of participants with minimal decay over time. 2019 Open forum infectious diseases Abstract HIV K103N 46 51 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. These mutations included: L109R, Q129R, M133L, S143L and D144E with overall prevalence of 18.9% (95% CI [9.5-34.2]). 2019 PeerJ Abstract HIV L109R;M133L;S143L 26;40;47 31;45;52 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C (p = 0.0013). 2019 BMC infectious diseases Abstract HIV K65R 13 17 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Overall HIVDR-level was 89.11% (90/101), with 83.2% harbouring M184 V (high-level 3TC/FTC-resistance) and only 1.98% (2/101) major HIVDR-mutations to ritonavir-boosted protease-inhibitors (PI/r). 2019 BMC infectious diseases Abstract HIV M184V 63 69 PI;PR 189;168 191;176 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41 L (22.77%), L210 W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)]. 2019 BMC infectious diseases Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 159;189;189;174;72;56;39;39 163;195;195;178;78;61;45;45 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Two (2/18; 11.1%) viruses from children treated with a first-line regimen had INSTI DRMs at codon 138 (E138K and E138T), which is known to harbour major resistance mutations, and also had the accessory mutations L74I, G140K, G140R and G163R. 2019 The Journal of antimicrobial chemotherapy Abstract HIV E138K;E138T;G140K;G140R;G163R;L74I 103;113;218;225;235;212 109;118;223;230;240;216 INSTI 78 83 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D is located near the HIV-1 polymerase active site; M230I is located near the hydrophobic region where NNRTIs bind. 2019 Journal of virology Abstract HIV M230I;G112D 56;0 61;5 NNRTI;Pol 107;32 113;42 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I alone caused a reduction in susceptibility to NNRTIs, while G112D alone did not. 2019 Journal of virology Abstract HIV G112D;M230I 66;0 71;5 NNRTI 52 58 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The G112D/M230I double mutant was less susceptible to NNRTIs than was M230I alone. 2019 Journal of virology Abstract HIV G112D;M230I;M230I 4;10;70 9;15;75 NNRTI 54 60 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The positioning of the nucleic acid is influenced by its interactions with the "primer grip" region and could be influenced by the M230I mutation.IMPORTANCE Although antiretroviral therapy (ART) is highly successful, drug-resistant variants can arise that blunt the efficacy of ART. 2019 Journal of virology Abstract HIV M230I 131 136 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Thus, M230I could directly interfere with NNRTI binding but G112D could not. 2019 Journal of virology Abstract HIV G112D;M230I 60;6 65;11 NNRTI 42 47 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Two mutations, G112D and M230I, were selected in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) by a novel nonnucleoside reverse transcriptase inhibitor (NNRTI). 2019 Journal of virology Abstract HIV G112D;M230I 15;25 20;30 NNRTI;NNRTI;RT;RT 185;138;53;76 190;173;74;78 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. We suggest that the mutations interact with each other via the bound nucleic acid substrate; the nucleic acid forms part of the polymerase active site, which is near G112D. 2019 Journal of virology Abstract HIV G112D 166 171 Pol 128 138 30905695 Effectiveness of switching from protease inhibitors to dolutegravir in combination with nucleoside reverse transcriptase inhibitors as maintenance antiretroviral therapy among HIV-positive patients. The presence of M184V/I mutation and other NRTI resistance-associated mutations (RAMs) did not increase the risk of virological failure in either group. 2019 International journal of antimicrobial agents Abstract HIV M184I;M184V 16;16 23;23 NRTI 43 47 30918485 The Utility of Efavirenz-based Prophylaxis Against HIV Infection. A Systems Pharmacological Analysis. Trough concentrations achieved after 600 mg once daily dosing (median: 2017 ng/mL, 95% CI:445-9830) and after reduced dose (400 mg) efavirenz (median: 1349ng/mL, 95% CI: 297-6553) provided complete protection against wild-type virus and the Y181C mutant, and median trough concentrations provided about 90% protection against the K103N and G190S mutants. 2019 Frontiers in pharmacology Abstract HIV G190S;K103N;Y181C 340;330;241 345;335;246 30918485 The Utility of Efavirenz-based Prophylaxis Against HIV Infection. A Systems Pharmacological Analysis. We predicted that plasma concentrations of 11, 36, 1287 and 1486ng/mL prevent 90% sexual transmissions with wild type and Y181C, K103N and G190S mutants, respectively. 2019 Frontiers in pharmacology Abstract HIV G190S;K103N;Y181C 139;129;122 144;134;127 30928089 Incidence and types of HIV-1 drug resistance mutation among patients failing first-line antiretroviral therapy. RESULTS: 103 cases were successfully amplified, and the main drug resistance mutations in the reverse transcriptase (RT) region were M184V (50.49%), K103N (28.16%), Y181C (25.24%), and K65R (27.18%), while no drug main resistance mutation was found in the protease (PR) region. 2019 Journal of pharmacological sciences Abstract HIV K103N;K65R;M184V;Y181C 149;185;133;165 154;189;138;170 RT;PR;PR;RT 94;256;266;117 115;264;268;119 30937190 Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India. Observed mutations were K219R, L74V, K219N, and Y181C. 2019 AIDS research and treatment Abstract HIV K219N;K219R;L74V;Y181C 37;24;31;48 42;29;35;53 30937190 Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India. The fact that both Y181C isolates are IDUs is important and represents 2/21 (~10%) NNRTI drug resistance. 2019 AIDS research and treatment Abstract HIV Y181C 19 24 NNRTI 83 88 30944182 Effects of the SOS (A501C/T605C) and DS (I201C/A433C) Disulfide Bonds on HIV-1 Membrane Envelope Glycoprotein Conformation and Function. Here we examine two previously reported Env mutants designed to be stabilized in this conformation by the introduction of artificial disulfide bonds: A501C/T605C (called SOS) and I201C/A433C (called DS). 2019 Journal of virology Abstract HIV A433C;A501C;I201C;T605C 185;150;179;156 190;155;184;161 Env 40 43 30946481 The rate of mother-to-child transmission of antiretroviral drug-resistant HIV strains is low in the Swiss Mother and Child HIV Cohort Study. HIV-sDRM (M184V 23%; K103N 4.5%; D67N 13.6%) occurred in 16/22 (73%) after 4 years, half of whom were treatment naïve. 2019 Swiss medical weekly Abstract HIV D67N;K103N;M184V 33;21;10 37;26;16 30946481 The rate of mother-to-child transmission of antiretroviral drug-resistant HIV strains is low in the Swiss Mother and Child HIV Cohort Study. Using stored plasma (n = 66) and mononuclear cell (n = 43) samples from the children, HIV-tDRM (M184V) was identified in 1 of 22 (4.5%) mothers (1/11 treated, 9%) and was followed by HIV-sDRM at 10 months of age. 2019 Swiss medical weekly Abstract HIV M184V 96 101 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. In normal HeLa-P4 cells, infection with HIV-1 bearing the A92E substitution in CA is inhibited by endogenous CypA and was inhibited to the same extent by expression of CypA mutants in CypA-null HeLa-P4 cells. 2019 Retrovirology Abstract HIV A92E 58 62 Capsid 79 81 30951600 Long-Term Safety and Efficacy of Dolutegravir in Treatment-Experienced Adolescents With Human Immunodeficiency Virus Infection: Results of the IMPAACT P1093 Study. HIV-1 genotypic drug resistance testing was available at time of failure from 6 participants; 1 had evolution in integrase resistance with E138T, S147G, and R263K mutations at week 192 and phenotypic dolutegravir resistance of a 5.1-fold change. 2020 Journal of the Pediatric Infectious Diseases Society Abstract HIV E138T;R263K;S147G 139;157;146 144;162;151 IN 113 122 30953643 HIV-1 Nef-GCC185 interaction regulates assembly of cellular protein complexes at TGN targeting MHC-I downregulation. Furthermore, the immunoprecipitations with PACS-2 and GCC185 in the presence or absence of Nef, Nef E4A mutant and Nef with CP-inhibitor divide the functional complex of Nef into Nef-dependent (AP-1 and PI3K) and GCC185-dependent complex (MHC-I and SFK). 2019 Life sciences Abstract HIV E4A 100 103 Nef;Nef;Nef;Nef;Nef;PI 91;96;115;170;179;203 94;99;118;173;182;205 30958309 Drug susceptibility and replication capacity of a rare HIV-1 subtype C protease hinge region variant. Additionally, enzyme assays were performed on the N37T V protease and a wild-type reference protease. 2019 Antiviral therapy Abstract HIV N37T 50 54 PR;PR 57;92 65;100 30958309 Drug susceptibility and replication capacity of a rare HIV-1 subtype C protease hinge region variant. CONCLUSIONS: Collectively, these data suggest that the N37T V mutation and insertion increases viral infectivity and decreases drug susceptibility. 2019 Antiviral therapy Abstract HIV N37T 55 59 30958309 Drug susceptibility and replication capacity of a rare HIV-1 subtype C protease hinge region variant. Furthermore, the N37T V protease displayed reduced catalytic processing compared with the SK154 protease. 2019 Antiviral therapy Abstract HIV N37T 17 21 PR;PR 24;96 32;104 30958309 Drug susceptibility and replication capacity of a rare HIV-1 subtype C protease hinge region variant. In this paper we investigate a South African HIV-1 subtype C Gag-protease that contains a hinge region mutation and insertion (N37T V). 2019 Antiviral therapy Abstract HIV N37T 127 132 PR;Gag 65;61 73;64 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. About half (49.1%, 27/55) of the HIV-1 strains with mutation presented as potential low-level resistant to NNRTI attributed to V179D/E. 2019 BMC infectious diseases Abstract HIV V179D;V179E 127;127 134;134 NNRTI 107 112 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. The most common HIV-1 mutation pattern for NNRTI and NRTI were V179D/E (10.1%, 32/317) and M184 V (2.8%, 9/317), respectively. 2019 BMC infectious diseases Abstract HIV M184V;V179D;V179E 91;63;63 97;70;70 NNRTI;NRTI 43;53 48;57 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Breakthroughs in the structural characterization of the HIV-1 Env trimer have previously been achieved by generating soluble and proteolytically cleaved trimers of gp140 Env that are stabilized by a disulfide bond, an isoleucine-to-proline substitution at residue 559 and a truncation at residue 664 (SOSIP.664 trimers)5,11-18. 2019 Nature Abstract HIV I559P 218 267 gp140;Env;Env 164;62;170 169;65;173 30977467 Evolution of HIV-1 drug resistance after virological failure of first-line antiretroviral therapy in Lusaka, Zambia. M184 mutations increased from 2% to 59% to 71%; K65R from 2% to 11% to 13%; 2 or more thymidine analogue mutations from 1% to 3% to 12%. 2019 Antiviral therapy Abstract HIV K65R 48 52 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). 2019 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M184V;Y181C 38;53;70 43;58;75 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). 2019 The Journal of antimicrobial chemotherapy Abstract HIV D67N;K103N;M184V;T215F;T215I;T215Y 59;29;44;76;76;76 63;34;49;85;85;85 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. It was also found that the drug resistance mutations Q148K/G140S and G118R/E138K significantly reduce the catalytic activity of IN_CRF and its sensitivity to the strand transfer inhibitor raltegravir. 2019 Acta naturae Abstract HIV E138K;G118R;G140S;Q148K 75;69;59;53 80;74;64;58 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Reduction in sensitivity to raltegravir was found to be much stronger in the case of double-mutation Q148K/G140S. 2019 Acta naturae Abstract HIV G140S;Q148K 107;101 112;106 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. Predominant major mutations were N155H (35.1%), Q148H/R (15.8%) and G140A/S (14%). 2019 Revista espanola de quimioterapia Abstract HIV G140A;G140S;N155H;Q148H;Q148R 68;68;33;48;48 75;75;38;55;55 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. The three main mutational pathways were described, with a predominance of N155H. 2019 Revista espanola de quimioterapia Abstract HIV N155H 74 79 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. G118R and G140R confer > 800-fold resistance to CAB and cross-resistance to all licensed integrase inhibitors. 2019 Nature communications Abstract HIV G140R;G118R 10;0 15;5 IN 89 98 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. We show integrase mutations G118R, E92G/Q, or G140R in plasma from 3/6 macaques as early as day 57, and identify G118R and E92Q in viruses from vaginal and rectal fluids. 2019 Nature communications Abstract HIV E92G;E92Q;E92Q;G118R;G118R;G140R 35;35;123;28;113;46 41;41;127;33;118;51 IN 8 17 31050739 New mechanisms of resistance in virological failure to protease inhibitors: selection of non-described protease, Gag and Gp41 mutations. In the gp41 region, the V321I mutation emerged inside the cytoplasmic tail (1 subtype A and 1 subtype B). 2019 The Journal of antimicrobial chemotherapy Abstract HIV V321I 24 29 gp41 7 11 31050739 New mechanisms of resistance in virological failure to protease inhibitors: selection of non-described protease, Gag and Gp41 mutations. Two patients showed the emergence of R286K in the gag region, outside of cleavage sites (2 CRF02_AG). 2019 The Journal of antimicrobial chemotherapy Abstract HIV R286K 37 42 Gag 50 53 31055063 HIV-1 matrix mutations that alter gag membrane binding modulate mature core formation and post-entry events. On the other hand, the L20K mutation, which increases Gag membrane binding, primarily decreased integrated DNA levels without affecting the viral components and morphology. 2019 Virology Abstract HIV L20K 23 27 Gag 54 57 31055063 HIV-1 matrix mutations that alter gag membrane binding modulate mature core formation and post-entry events. The V6R mutation, which decreases Gag membrane binding, modified Gag processing and core morphogenesis and impaired core uncoating, reverse transcription, and viral DNA integration. 2019 Virology Abstract HIV V6R 4 7 RT;Gag;Gag 132;34;65 153;37;68 31080115 Naturally occurring NS5A and NS5B resistant associated substitutions in HCV and HCV/HIV patients in iranian population. Clinically relevant substitutions were included V321A/I, C316Y, S282R and L159F. 2019 Clinics and research in hepatology and gastroenterology Abstract HIV C316Y;L159F;S282R;V321A;V321I 57;74;64;48;48 62;79;69;55;55 31080115 Naturally occurring NS5A and NS5B resistant associated substitutions in HCV and HCV/HIV patients in iranian population. In HCV cases, clinically relevant RASs were L28M followed by M28Vand Q30H and Y93H/N. 2019 Clinics and research in hepatology and gastroenterology Abstract HIV L28M;M28V;Q30H;Y93H;Y93N 44;61;69;78;78 48;65;73;84;84 31080115 Naturally occurring NS5A and NS5B resistant associated substitutions in HCV and HCV/HIV patients in iranian population. In HCV/HIV subjects, clinically relevant RASs were Y93H/N followed by L28M and P58T and M28V/T and Q30R. 2019 Clinics and research in hepatology and gastroenterology Abstract HIV L28M;M28T;M28V;P58T;Q30R;Y93H;Y93N 70;88;88;79;99;51;51 74;94;94;83;103;57;57 31080115 Naturally occurring NS5A and NS5B resistant associated substitutions in HCV and HCV/HIV patients in iranian population. The major S282T mutation was not observed. 2019 Clinics and research in hepatology and gastroenterology Abstract HIV S282T 10 15 31090546 E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection. CONCLUSION: E157Q substitution, reducing raltegravir and elvitegravir activity, was frequently found in acute/recent HIV cases. 2019 AIDS (London, England) Abstract HIV E157Q 12 17 31090546 E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection. Polymorphic substitutions that reduce InSTIs activity have been described, with E157Q being one of the most frequently found. 2019 AIDS (London, England) Abstract HIV E157Q 80 85 INSTI 38 44 31090546 E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection. RESULTS: In six out of 67 consecutive patients (8.95%, 95% confidence interval 4.17-18.19) with acute/recent HIV infection, strains carrying the E157Q InSTI substitution were detected. 2019 AIDS (London, England) Abstract HIV E157Q 145 150 INSTI 151 156 HIV infections 109 122 31090546 E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection. This study aimed to evaluate the prevalence of E157Q substitution in newly diagnosed acute/recent HIV cases and the presence of transmission clusters. 2019 AIDS (London, England) Abstract HIV E157Q 47 52 31091477 Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains. Compound 4b had EC50 values of 3.5 nM and 66 nM against non-nucleoside reverse transcriptase inhibitor-resistant strains bearing the RT E138K and RES056 mutations. 2019 European journal of medicinal chemistry Abstract HIV E138K 136 141 NNRTI;RT 56;133 92;135 31091477 Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains. Moreover, most of the compounds maintained high activity (low-micromolar EC50 values) against strains bearing the reverse transcriptase (RT) E138K mutation. 2019 European journal of medicinal chemistry Abstract HIV E138K 139 146 RT;RT 114;137 135;139 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. Instead, the basic amine at P2 of inhibitor together with mutation V82I induces two alternate conformations for the side chain of Arg8 with new interactions with inhibitor and Leu10. 2019 Biochemical and biophysical research communications Abstract HIV V82I 67 71 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. This study examines the effects of four investigational inhibitors against HIV-1 protease with drug resistant mutations of V32I, I47V and V82I (PRTri) that model the inhibitor-binding site of HIV-2 protease. 2019 Biochemical and biophysical research communications Abstract HIV I47V;V32I;V82I 129;123;138 133;127;142 PR;PR 81;198 89;206 31102693 Follow on-based optimization of the biphenyl-DAPYs as HIV-1 nonnucleoside reverse transcriptase inhibitors against the wild-type and mutant strains. Specifically, compound 30, which had the highest selectivity index (SI = 16094) and the best anti-reverse transcriptase ability (IC50 = 39 nM), displayed marked inhibitory activity (EC50 = 13.5, 9.4, 17.0, 52.0, and 58.2 nM) against WT, K103N, E138K, L100I, Y181C mutants and moderate activity against double mutants. 2019 Bioorganic chemistry Abstract HIV E138K;K103N;L100I;Y181C 244;237;251;258 249;242;256;263 RT 98 119 31109980 An Evolutionary Model-Based Approach To Quantify the Genetic Barrier to Drug Resistance in Fast-Evolving Viruses and Its Application to HIV-1 Subtypes and Integrase Inhibitors. A supplementary analysis for HIV-1 reverse transcriptase inhibitors identified a lower genetic barrier for K65R in subtype C through differential codon usage not reported before. 2019 Antimicrobial agents and chemotherapy Abstract HIV K65R 107 111 RT 35 56 31109980 An Evolutionary Model-Based Approach To Quantify the Genetic Barrier to Drug Resistance in Fast-Evolving Viruses and Its Application to HIV-1 Subtypes and Integrase Inhibitors. While we confirm the lower genetic barrier of subtype B for G140S, we convincingly discard a similar effect previously suggested for G140C. 2019 Antimicrobial agents and chemotherapy Abstract HIV G140C;G140S 133;60 138;65 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. M184V, M41L, D67N, G190A, A98G, and K103N were the most common mutations seen. 2019 Journal of the International Association of Providers of AIDS Care Abstract HIV A98G;D67N;G190A;K103N;M41L;M184V 26;13;19;36;7;0 30;17;24;41;11;5 31119759 Detection of human immunodeficiency virus Type 1 phylogenetic clusters with multidrug resistance mutations among 2011 to 2017 blood donors from the highly endemic Northern Brazilian Amazon. The other two transmission clades comprised only three and two sequences from HEMOAM sharing the E138A NNRTI mutation. 2019 Transfusion Abstract HIV E138A 97 102 NNRTI 103 108 31119759 Detection of human immunodeficiency virus Type 1 phylogenetic clusters with multidrug resistance mutations among 2011 to 2017 blood donors from the highly endemic Northern Brazilian Amazon. This cluster was characterized by NRTI (D67N, T69D, T215S/F/L, K219Q) and NNRTI (K101H, K103 N, G190A) mutations. 2019 Transfusion Abstract HIV D67N;G190A;K101H;K103N;K219Q;T215F;T215L;T215S;T69D 40;96;81;88;63;52;52;52;46 44;101;86;94;68;61;61;61;50 NNRTI;NRTI 74;34 79;38 31141685 A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation. A gp41 substitution, E658K, functions as the major determinant for these properties. 2019 Cell reports Abstract HIV E658K 21 26 gp41 2 6 31146045 Stable level of HIV transmitted drug resistance in Estonia despite significant scale-up of antiretroviral therapy. CONCLUSIONS: TDR remained stable at a moderate level in Estonia, K103N is the main SDRM with only one transmission-pair detected. 2019 Infection, genetics and evolution Abstract HIV K103N 65 70 31146045 Stable level of HIV transmitted drug resistance in Estonia despite significant scale-up of antiretroviral therapy. K103 N (8/15, 53%) was the most common SDRM. 2019 Infection, genetics and evolution Abstract HIV K103N 0 6 31160281 Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase. EFV and RPV bound more tightly to Y181F RT-T/P. 2019 Antimicrobial agents and chemotherapy Abstract HIV Y181F 34 39 RT 40 42 31160281 Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase. Furthermore, inhibitor-bound Y181F RT-T/P was less efficient than the WT complex in incorporating the next correct dNTP, and this could be attributed to increased mobility of Y181F RT on the T/P substrate. 2019 Antimicrobial agents and chemotherapy Abstract HIV Y181F;Y181F 29;175 34;180 RT;RT 35;181 37;183 31160281 Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase. In the presence of saturating concentrations of inhibitor, the Y181C RT-T/P complex incorporated the next correct deoxynucleoside triphosphate (dNTP) more efficiently than the wild-type (WT) complex, and this phenotype correlated with decreased mobility of the RT on the T/P substrate. 2019 Antimicrobial agents and chemotherapy Abstract HIV Y181C 63 68 RT;RT 69;261 71;263 31160281 Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase. Interestingly, we found that the Y181F substitution in RT-which represents a transitional mutation between Y181 and Y181I/V, or a partial revertant-conferred hypersusceptibility to EFV and RPV at both the virus and enzyme levels. 2019 Antimicrobial agents and chemotherapy Abstract HIV Y181F;Y181I;Y181V 33;116;116 38;123;123 RT 55 57 31160281 Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase. Substitutions at residue Y181 in HIV-1 reverse transcriptase (RT), in particular, Y181C, Y181I, and Y181V, are associated with nonnucleoside RT inhibitor (NNRTI) cross-resistance. 2019 Antimicrobial agents and chemotherapy Abstract HIV Y181C;Y181I;Y181V 82;89;100 87;94;105 RT;NNRTI;RT;RT 39;155;62;141 60;160;64;143 31160281 Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase. Using pre-steady-state kinetics, we found that the dissociation constant (Kd ) values for inhibitor binding to the Y181C and Y181I RT-template/primer (T/P) complexes were significantly reduced. 2019 Antimicrobial agents and chemotherapy Abstract HIV Y181C;Y181I 115;125 120;130 RT 131 133 31167922 A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing. A cell-free assay showed that the R143A mutant partially counteracted the capsid-destabilizing activity of PF74, pointing to capsid stabilization as a resistance mechanism for the R143A mutant. 2019 Journal of virology Abstract HIV R143A;R143A 34;180 39;185 Capsid;Capsid 74;125 80;131 31167922 A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing. A single mutation, R143A, in the capsid protein conferred resistance to high concentrations of PF74, without affecting capsid binding to PF74. 2019 Journal of virology Abstract HIV R143A 19 24 Capsid;Capsid 33;119 39;125 31167922 A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing. Imaging assays revealed delayed uncoating kinetics of this T/F variant and the R143A mutant. 2019 Journal of virology Abstract HIV R143A 79 84 31167922 A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing. In monocytic THP-1 cells, the R143A virus, but not the wild-type virus, suppressed cGAS-dependent innate immune activation. 2019 Journal of virology Abstract HIV R143A 30 35 31167922 A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing. We found that a naturally occurring transmitted founder (T/F) variant shares the same properties as the R143A mutant with respect to PF74 resistance and DNA sensing. 2019 Journal of virology Abstract HIV R143A 104 109 31169022 Trends in HIV-1 Drug Resistance Mutations from a U.S. Reference Laboratory from 2006 to 2017. INSTI DRM Q148H/K/R declined from 39.3% (2010) to 13.8% (2017). 2019 AIDS research and human retroviruses Abstract HIV Q148H;Q148K;Q148R 10;10;10 19;19;19 INSTI 0 5 31169022 Trends in HIV-1 Drug Resistance Mutations from a U.S. Reference Laboratory from 2006 to 2017. K103N/S/T declined from 42.5% in 2012 to 36.4% in 2017. 2019 AIDS research and human retroviruses Abstract HIV K103N;K103S;K103T 0;0;0 9;9;9 31169022 Trends in HIV-1 Drug Resistance Mutations from a U.S. Reference Laboratory from 2006 to 2017. M184V/I decreased from 48.3% to 29.4%. 2019 AIDS research and human retroviruses Abstract HIV M184I;M184V 0;0 7;7 31169022 Trends in HIV-1 Drug Resistance Mutations from a U.S. Reference Laboratory from 2006 to 2017. Prevalence of elvitegravir-associated DRMs T66A/I/K, E92Q, S147G, and the dolutegravir-associated DRM R263K increased. 2019 AIDS research and human retroviruses Abstract HIV E92Q;R263K;S147G;T66A;T66I;T66K 53;102;59;43;43;43 57;107;64;51;51;51 31169022 Trends in HIV-1 Drug Resistance Mutations from a U.S. Reference Laboratory from 2006 to 2017. Rilpivirine and etravirine DRMs E138A/Q/R and E138K increased from 4.9% and 0.4% to 9.7% and 1.7%, respectively. 2019 AIDS research and human retroviruses Abstract HIV E138A;E138K;E138Q;E138R 32;46;32;32 41;51;41;41 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. G48V resistance mutation induces curled flap tips in PRS17-D25N structure. 2019 ACS omega Abstract HIV G48V 0 4 PR 53 55 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The loss of beta-branched side chain by V82S mutation initiates a shift in 80's loop and reshapes the S3/S3' subsite, which enhances substrate binding with new hydrogen bonds and van der Waals interactions that are absent in the wild-type structures. 2019 ACS omega Abstract HIV V82S 40 44 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The steric hindrance caused by G48V mutation in the flap of PRS17 contributes to altered binding interactions of P3 Arg, P4' norleucine of CA-p2, and P4 and P3' of p2-NC with the addition of new hydrogen bonds and van der Waals contacts. 2019 ACS omega Abstract HIV G48V 31 35 PR;Capsid;NC 60;139;167 62;141;169 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Amongst the genetic mutations resistant to NNRTIs, G190S mutation was the highest (51.2%), K101HQ mutation was 39.5% and Y181I mutation was 34.9%. 2019 Infection and drug resistance Abstract HIV G190S;K101H;K101Q;Y181I 51;91;91;121 56;97;97;126 NNRTI 43 49 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. In genetic mutations in PIs, M36I and K20R mutations made up 9.3%. 2019 Infection and drug resistance Abstract HIV K20R;M36I 38;29 42;33 PI 24 27 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. In genetic mutations to NRTIs, M184V mutation was 88.4%. 2019 Infection and drug resistance Abstract HIV M184V 31 36 NRTI 24 29 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. In thymidine analogue mutations, K70R mutation was the most common (37.2%), followed by D67N, T215F and T69N mutations (27.9%, 27.9% and 25.6%, respectively). 2019 Infection and drug resistance Abstract HIV D67N;K70R;T215F;T69N 88;33;94;104 92;37;99;108 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. The single point mutations in tetherin at positions L23Y, L24T, and P40T, and triple mutations at {L22S, F44Y, L37I} and {L23T, L37T, T45I}, while single point mutations in Vpu at positions A19H and W23Y and triplet of mutations at {V10K, A11L, A19T}, {V14T, I18T, I26S}, and {A11T, V14L, A15T} have revealed no polar contacts with minimal hydrophobic interactions between Vpu and tetherin, resulting in reduced binding affinity. 2019 Medical sciences (Basel, Switzerland) Abstract HIV A11L;A11T;A15T;A19H;A19T;F44Y;I18T;I26S;L22S;L23T;L23Y;L24T;L37I;L37T;P40T;T45I;V10K;V14L;V14T;W23Y 239;277;289;190;245;105;259;265;99;122;52;58;111;128;68;134;233;283;253;199 243;281;293;194;249;109;263;269;103;126;56;62;115;132;72;138;237;287;257;203 Vpu;Vpu 173;373 176;376 31240860 Lamivudine-based maintenance antiretroviral therapies in patients living with HIV-1 with suppressed HIV RNA: derivation of a predictive score for virological failure. A score of 2 was assigned to non-B viral subtype, 3 to residual viraemia >= 20 copies/mL, >= 10 previous therapeutic lines and African ethnicity, 4 to baseline CD4 count < 200 cells/muL, and 7 to the presence of at least one RAM (excluding M184V). 2019 HIV medicine Abstract HIV M184V 240 245 31240860 Lamivudine-based maintenance antiretroviral therapies in patients living with HIV-1 with suppressed HIV RNA: derivation of a predictive score for virological failure. RESULTS: During a median 2 years of follow-up time, 35 VFs occurred; predictors of VF were baseline residual HIV RNA between 20 and 36 copies/mL, African ethnicity, >= 10 therapeutic lines, the presence of at least one resistance-associated mutation (RAM) for resistance to current drugs (excluding M184V), a non-B viral subtype and a baseline CD4 count < 200 cells/muL. 2019 HIV medicine Abstract HIV M184V 299 304 31242157 HIV-1 Antiretroviral Resistance in Cuba, 2009-2014. K65R and K101E mutations were significantly more frequent in subtype C, L210W in CRF19_cpx, and M47V/I in CRF BGs (20, 23, 24). 2018 MEDICC review Abstract HIV K101E;L210W;M47I;M47V;K65R 9;72;96;96;0 14;77;102;102;4 31255705 Structural and Thermodynamic Analysis of HIV-1 Fusion Inhibition Using Small gp41 Mimetic Proteins. Here, we investigated two covNHR variants differing in two mutations, V10E and Q123R (equivalent to V38E and Q40R in gp41 sequence) that reproduce the effect of HIV-1 mutations associated with resistance to fusion inhibitors, such as T20 (enfuvirtide). 2019 Journal of molecular biology Abstract HIV Q123R;Q40R;V10E;V38E 79;109;70;100 84;113;74;104 gp41 117 121 31255794 HIV-1 drug resistance surveillance among parturient women on anti-retroviral therapy in the Eastern Cape, South Africa: Implications for elimination of mother-to-child transmission. Among the parturient women on EFV-based regimen treatment; 79.1% already had K103 N while nine patients on protease inhibitor-based regimen still harboured K103 N. 2019 Journal of clinical virology Abstract HIV K103N;K103N 77;156 83;162 PR 107 115 31255794 HIV-1 drug resistance surveillance among parturient women on anti-retroviral therapy in the Eastern Cape, South Africa: Implications for elimination of mother-to-child transmission. The majority of the M184 V mutations were observed in parturient women on first line regimen (n = 23; 82.1%). 2019 Journal of clinical virology Abstract HIV M184V 20 26 31255794 HIV-1 drug resistance surveillance among parturient women on anti-retroviral therapy in the Eastern Cape, South Africa: Implications for elimination of mother-to-child transmission. The predominant DRMs were K103 N (n = 43; 74.1%), M184 V (n = 28; 48.3%) and K65R (n = 11; 19%). 2019 Journal of clinical virology Abstract HIV K103N;K65R;M184V 26;77;50 32;81;56 31257432 Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. 2019 The Journal of antimicrobial chemotherapy Abstract HIV K103N;M184I;M184V 64;34;34 69;41;41 NNRTI;NRTI 82;54 88;59 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. A high rate of K65R was identified only in TDF treated patients (35.7%; 50.0%, respectively). 2019 BMC infectious diseases Abstract HIV K65R 15 19 31266578 Characterisation of protease resistance mutations in a South African paediatric cohort with virological failure, 2011 - 2017. The most frequent major PI mutations were V82A (76.2%), M46I/M46L (76.2%), I54V (62.0%) and L76V (33.3%). 2019 South African medical journal Abstract HIV I54V;L76V;M46I;M46L;V82A 75;92;56;56;42 79;96;60;60;46 PI 24 26 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. HIV resistance testing was available for 78% (28/38), of whom 82.1% (23/28) had at least one major drug resistance mutation (DRM), most frequently M184V (70%, 16/23) and K103N (65%, 15/23). 2019 Sexually transmitted infections Abstract HIV K103N;M184V 170;147 175;152 31269034 Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study. In both scenarios, we find comparably high prevalence (~80%) of acquired NNRTI-associated, M184V and K65R mutations. 2019 PloS one Abstract HIV K65R;M184V 101;91 105;96 NNRTI 73 78 31269034 Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study. METHODS: We constructed a stochastic individual-based model and simulated scenarios of ART implementation, either CD4-based (threshold < 500 cells/mL) or Fast-track (81% coverage by 2020), with consideration of major drug-associated mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). 2019 PloS one Abstract HIV K65R;M184V 251;244 255;249 NNRTI;NNRTI 260;308 296;313 31273377 Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring. Tenofovir-resistance mutations K65R and K70G/E or >=3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure. 2019 The Journal of antimicrobial chemotherapy Abstract HIV K65R;K70E;K70G;L210W;M41L 31;40;40;113;104 35;46;46;118;108 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. The compound demonstrates low nanomolar potency against both WT and Y181C HIV-1 RT in in vitro and cellular assays. 2019 Bioorganic & medicinal chemistry letters Abstract HIV Y181C 68 73 RT 80 82 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. The development of efficacious NNRTIs for HIV/AIDS therapy is commonly met with the emergence of drug resistant strains, including the Y181C variant. 2019 Bioorganic & medicinal chemistry letters Abstract HIV Y181C 135 140 NNRTI 31 37 AIDS 46 50 31307042 HIV-1 Integrase Resistance among Highly Antiretroviral Experienced Patients from Morocco. The major INSTI resistance mutations at positions 66, 92, 118, 138, 140, 143, 147, 148, 155, and 263 were absent, while two accessory mutations, L74M/I, known to have no clinical impact to INSTIs in the absence of the major resistance mutations, were detected in three samples (3.84%; two CRF02_AG and one CRF01_AE). 2019 Intervirology Abstract HIV L74I;L74M 145;145 151;151 INSTI;INSTI 10;189 15;195 31311021 HIV-1 Drug Resistance Mutations among Antiretroviral Drug-Experienced Patients in the South of Iran. M184V (40.9%) and K103N (25%), respectively related to NRTI and nonnucleoside reverse-transcriptase inhibitor (NNRTI), were the mutations with the highest frequencies. 2019 Intervirology Abstract HIV K103N;M184V 18;0 23;5 NNRTI;NNRTI;NRTI 64;111;55 99;116;59 31330378 Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors. Before INSTI treatment one patient harboured the major INSTI-RM R263K and three patients the accessory INSTI-RMs T97A. 2020 Journal of global antimicrobial resistance Abstract HIV R263K;T97A 64;113 69;117 INSTI;INSTI;INSTI 7;55;103 12;60;108 31330378 Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors. The major INSTI-RMs that more frequently emerged were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), and Y143C (4.7%). 2020 Journal of global antimicrobial resistance Abstract HIV G140S;N155H;Q148H;Y143C;Y143R 70;55;98;116;84 75;60;103;121;89 INSTI 10 15 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In this study, we investigated the interdependence between the L89V and L90M mutations and their effects on DRV binding. 2019 Biochemistry Abstract HIV L89V;L90M 63;72 67;76 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Molecular dynamics simulations of these DRV-bound protease variants reveal how the L90M mutation induces structural changes throughout the enzyme that undermine the binding interactions. 2019 Biochemistry Abstract HIV L90M 83 87 PR 50 58 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The enzymatic assays revealed that the KY(V89L) variant, with methionine at residue 90, is highly resistant, but its catalytic function is compromised. 2019 Biochemistry Abstract HIV V89L 42 46 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The focus of our investigation is a patient-derived isolate, with 24 mutations that we call "KY"; this variant includes the L89V and L90M mutations. 2019 Biochemistry Abstract HIV L89V;L90M 124;133 128;137 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Three additional KY variants with back-mutations, KY(V89L), KY(M90L), and the KY(V89L/M90L) double mutation, were used to experimentally assess the individual and combined effects of these mutations on DRV inhibition and substrate processing. 2019 Biochemistry Abstract HIV M90L;M90L;V89L;V89L 63;86;53;81 67;90;57;85 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. When a leucine to valine mutation at residue 89 is present simultaneously with the L90M mutation, a rescue of catalytic efficiency is observed. 2019 Biochemistry Abstract HIV L89V;L90M 7;83 47;87 31389026 Antiviral activity of HIV-1 integrase strand-transfer inhibitors against mutants with integrase resistance-associated mutations and their frequency in treatment-naive individuals. Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-naive subjects with no impact on INSTI susceptibility. 2019 Journal of medical virology Abstract HIV E157Q;M50I;S119G;S119P;S119R;S119T 62;39;45;45;45;45 67;43;56;56;56;56 INSTI;INSTI;IN 20;136;90 25;141;92 31389026 Antiviral activity of HIV-1 integrase strand-transfer inhibitors against mutants with integrase resistance-associated mutations and their frequency in treatment-naive individuals. When each combined with major INSTI-R mutation, M50I, S119P, and E157Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir. 2019 Journal of medical virology Abstract HIV E157Q;M50I;S119P 65;48;54 70;52;59 INSTI 30 35 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Herein, we report the effect of nine FDA approved protease inhibitor drugs against a new HIV-1 subtype C mutant protease, E35D G S. 2019 Journal of enzyme inhibition and medicinal chemistry Abstract HIV E35D 122 126 PR;PR 50;112 58;120 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The mutant has five mutations, E35D, two insertions, position 36 (G and S), and D60E. 2019 Journal of enzyme inhibition and medicinal chemistry Abstract HIV D60E;E35D 80;31 84;35 31422059 Dual therapy with ritonavir-boosted protease inhibitor (PI) plus lamivudine versus triple therapy with ritonavir-boosted PI plus two nucleos(t)ide reverse-transcriptase inhibitor in HIV-infected patients with viral suppression. Nineteen patients (3 [3.2%] in dual-therapy and 16 [7.6%] in triple-therapy group) developed virologic failure, with none having emergent M184V resistance-associated mutation. 2019 Journal of microbiology, immunology, and infection Abstract HIV M184V 138 143 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. At week 48, 98% (561/570) of all BIC/FTC/TAF-treated participants versus 98% (213/217) with pre-existing resistance and 96% (52/54) with archived M184V/I had HIV-1 RNA <50 copies/mL. 2019 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 146;146 153;153 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. CONCLUSIONS: Pre-existing resistance substitutions, notably M184V/I, were unexpectedly common among suppressed participants who switched to BIC/FTC/TAF. 2019 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 60;60 67;67 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. High rates of virological suppression were maintained in the overall study population and in those with pre-existing resistance, including M184V/I, for up to 48 weeks of BIC/FTC/TAF treatment with no resistance development. 2019 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 139;139 146;146 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Pre-switch NRTI resistance was detected in 16% (89/543) of BIC/FTC/TAF-treated participants, with M184V or M184I detected by proviral genotyping in 10% (54/543). 2019 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 107;98 112;103 NRTI 11 15 31434039 Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing. Furthermore, some compounds maintained excellent activity against various single HIV-1 mutants (L100I, K103 N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC50 values in low-micromolar concentration ranges. 2019 European journal of medicinal chemistry Abstract HIV F227L;E138K;K103N;L100I;V106A;Y181C 155;111;103;96;161;118 160;116;109;101;166;123 31434039 Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing. Notably, 34 displayed outstanding potency against F227L/V106A (EC50 = 0.094 muM), and also showed exceptional activity against E138K (EC50 = 0.014 muM), L100I (EC50 = 0.011 muM) and K103 N (EC50 = 0.025 muM). 2019 European journal of medicinal chemistry Abstract HIV E138K;F227L;K103N;L100I;V106A 127;50;182;153;56 132;55;188;158;61 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. 2019 BMC infectious diseases Abstract HIV K103N;K103R;V179D 30;49;41 36;54;46 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. 2019 BMC infectious diseases Abstract HIV K103N;K103R;V179D 32;111;103 38;116;108 HIV infections 5 17 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. The most frequent mutations detected were K103N (12.9%), G190A (6.4%) and Y181C (4.8%). 2019 PloS one Abstract HIV G190A;K103N;Y181C 57;42;74 62;47;79 31491787 Lack of HIV-1 integrase inhibitor resistance among 392 antiretroviral-naive individuals in a tertiary care hospital in Beijing, China. Two individuals harbored INSTI accessory mutations E157Q/T97A were detected for the first time. 2019 AIDS (London, England) Abstract HIV E157Q;T97A 51;58 56;61 INSTI 25 30 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation dramatically accelerated the kinetics of reverse transcription and initiation of uncoating of the RGDA/Q112D virus in the presence or absence of IFN-beta, whereas the G94D/G116R mutations affected reverse transcription only in the presence of IFN-beta, most consistent with a mechanism of the disruption of binding to an unknown IFN-beta-regulated host factor. 2019 Journal of virology Abstract HIV G116R;G94D;Q112D;Q4R 189;184;115;4 194;188;125;7 RT;RT 58;214 79;235 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. This variant, called the RGDA/Q112D virus, contains multiple mutations in CA: H87R, A88G, P90D, P93A, and Q112D. 2019 Journal of virology Abstract HIV A88G;H87R;P90D;P93A;Q112D;Q112D 84;78;90;96;25;106 88;82;94;100;35;111 Capsid 74 76 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. To investigate how an IFN-hypersensitive virus can evolve to overcome IFN-beta-mediated blocks targeting the viral capsid, we adapted the RGDA/Q112D virus in IFN-beta-treated cells. 2019 Journal of virology Abstract HIV Q112D 138 148 Capsid 115 121 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We successfully isolated IFN-beta-resistant viruses which contained either a single Q4R substitution or the double amino acid change G94D/G116R. 2019 Journal of virology Abstract HIV G116R;G94D;Q4R 138;133;84 143;137;87 31516033 Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials. In AMBER, the nucleos(t)ide analog reverse transcriptase inhibitor (N(t)RTI) RAM M184I/V was identified in HIV-1 of one participant during D/C/F/TAF treatment. 2020 AIDS research and human retroviruses Abstract HIV M184I;M184V 81;81 88;88 NRTI;NRTI 68;14 75;56 31516033 Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials. M184V was detected pretreatment as a minority variant (9%). 2020 AIDS research and human retroviruses Abstract HIV M184V 0 5 31516033 Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. 2020 AIDS research and human retroviruses Abstract HIV M184I;M184V 22;22 29;29 31518723 Transmitted drug resistance mutations and trends of HIV-1 subtypes in treatment-naive patients: A single-centre experience. Transmitted INSTI mutations (Q148H and G140S) responsible for high-level resistance to raltegravir and elvitegravir and intermediate resistance to dolutegravir and bictegravir were found, for the first time, in two individuals. 2020 Journal of global antimicrobial resistance Abstract HIV G140S;Q148H 39;29 44;35 INSTI 12 17 31521809 Long-term data on the efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multi-centre cohort of HIV-1-infected, virologically suppressed patients. In patients with time of virological suppression <88 months, the rate of VF was higher in the presence of the M184V mutation. 2019 International journal of antimicrobial agents Abstract HIV M184V 110 115 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. A cryo-EM structure of CH235 UCA bound to Man5-enriched CH505.N279K.G458Y.SOSIP.664 revealed interactions of the antibody light chain complementarity determining region 3 (CDR L3) with the engineered Env loops D and V5. 2019 PLoS pathogens Abstract HIV G458Y 68 73 Env 200 203 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Two Env mutations were identified, one in loop D (N279K) and another in V5 (G458Y), that acted synergistically to render autologous CH505 transmitted/founder virus susceptible to neutralization by CH235 UCA. 2019 PLoS pathogens Abstract HIV G458Y;N279K 76;50 81;55 Env 4 7 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. PI and INSTI TDR remained low, with noted E138A prevalence of 2.9%. 2019 Heliyon Abstract HIV E138A 42 47 INSTI;PI 7;0 12;2 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The co-occurrence network revealed that the major resistance pathways N155H and Q148HR share more mutations with each other than with the Y143R pathway, this observation corroborates the fact that the N155H pathway is most commonly converted into Q148HRK than into Y143RCH pathway in patients' isolates. 2019 Frontiers in microbiology Abstract HIV N155H;N155H;Q148H;Q148H;Q148K;Q148R;Q148R;Y143C;Y143H;Y143R;Y143R 70;201;80;247;247;80;247;265;265;138;265 75;206;86;254;254;86;254;272;272;143;272 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The network and the structure analysis also support the hypothesis that the resistance-related E138K mutation may be a mechanism to compensate for mutations in neighbor lysine residues to maintain DNA binding. 2019 Frontiers in microbiology Abstract HIV E138K 95 100 31576459 Circulation of multiple subtypes (A, G and CRFs 02_AG) of human immunodeficiency virus type 1 (HIV-1) in selected districts of Punjab province, Pakistan. Although we screened 18 samples for drug-resistance-associated mutations, except for an accessory mutation (M46K) in the protease (PR) region in one subject, we found a lack of drug-resistance-associated substitutions in the PR region. 2019 Archives of virology Abstract HIV M46K 108 112 PR;PR;PR 121;131;225 129;133;227 31576459 Circulation of multiple subtypes (A, G and CRFs 02_AG) of human immunodeficiency virus type 1 (HIV-1) in selected districts of Punjab province, Pakistan. On the other hand, we found two subjects (2/18) carrying a resistance-associated mutation (V106I) conferring a low level of resistance against non-nucleoside reverse transcriptase inhibitors. 2019 Archives of virology Abstract HIV V106I 91 96 NNRTI 143 179 31584370 Molecular Genetics and the Incidence of Transmitted Drug Resistance Among Pre-Treatment HIV-1 Infected Patients in the Eastern Cape, South Africa. Four major protease inhibitor (PI) related mutations (I54V, V82A/L, L76V and L90M) were observed in seven patients while several other minor and accessory PIs were also identified. 2019 Current HIV research Abstract HIV I54V;L76V;L90M;V82A;V82L 54;68;77;60;60 58;72;81;66;66 PR;PI;PI 11;31;155 19;33;158 31584370 Molecular Genetics and the Incidence of Transmitted Drug Resistance Among Pre-Treatment HIV-1 Infected Patients in the Eastern Cape, South Africa. K103N/S, V106M and M184V were the most common mutations identified among the viral sequences. 2019 Current HIV research Abstract HIV K103N;K103S;M184V;V106M 0;0;19;9 7;7;24;14 31599568 Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. 2020 ACS infectious diseases Abstract HIV E138K;E138K 34;73 39;78 NNRTI 101 106 31599568 Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 2020 ACS infectious diseases Abstract HIV K103N 208 213 31599568 Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. 2020 ACS infectious diseases Abstract HIV E138K;K103N 98;109 103;114 31611362 Comparable In Vitro Activities of Second-Generation HIV-1 Integrase Strand Transfer Inhibitors (INSTIs) on HIV-1 Clinical Isolates with INSTI Resistance Mutations. In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q148H/K/R plus one to two additional INSTI mutations. 2019 Antimicrobial agents and chemotherapy Abstract HIV Q148H;Q148K;Q148R 228;228;228 237;237;237 INSTI;INSTI 82;265 87;270 31617907 Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance. Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K. 2020 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138K;E138T;E92G;E92Q;F121Y;G118R;G140A;G140C;G140S;N155H;Q148H;Q148K;Q148R;R263K;S147G;S230R;T66A;T66I;T66K;Y143C;Y143H;Y143R;Y143S 187;187;187;165;165;180;173;198;198;198;240;229;229;229;257;222;247;155;155;155;209;209;209;209 196;196;196;171;171;185;178;207;207;207;245;238;238;238;262;227;252;163;163;163;220;220;220;220 INSTI;INSTI 31;109 36;114 31619555 SOS and IP Modifications Predominantly Affect the Yield but Not Other Properties of SOSIP.664 HIV-1 Env Glycoprotein Trimers. The prototypic design, designated BG505 SOSIP.664, incorporates an intersubunit disulfide bond (SOS) to covalently link the gp120 and gp41 ectodomain (gp41ECTO) subunits and a point substitution, I559P (IP), to further stabilize the gp41ECTO components. 2019 Journal of virology Abstract HIV I559P 196 201 gp41;gp41;gp120;gp41 151;233;124;134 155;237;129;138 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. H219Q increased viral replication capacity and reduced susceptibility of poorly growing viruses. 2019 PloS one Abstract HIV H219Q 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The first type was in the capsid C-terminal domain and downstream SP1 region (including (Gag numbering) R286K, A326T, T332S/N, I333V and V370A/M). 2019 PloS one Abstract HIV A326T;I333V;R286K;T332N;T332S;V370A;V370M 111;127;102;118;118;137;137 116;132;109;125;125;144;144 Capsid;Gag;SP1 26;89;66 32;92;69 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The second, was an R41G substitution in viral protease that occurred with V362I. 2019 PloS one Abstract HIV R41G;V362I 19;74 23;79 PR 46 54 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The third was seen in the capsid N-terminal domain, within the cyclophilin A binding domain (V218A/M, H219Q and G221E). 2019 PloS one Abstract HIV G221E;H219Q;V218A;V218M 112;102;93;93 117;107;100;100 Capsid 26 32 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Two key substitutions, A364V or V362I, were selected, the latter requiring secondary substitutions to reduce susceptibility to GSK3532795. 2019 PloS one Abstract HIV A364V;V362I 23;32 28;37 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. In this study, we use molecular dynamics (MD) simulations and advanced MD techniques including temperature acceleration and string method in collective variables to study the conformational changes associated with substrate unbinding of both wild-type and F99Y mutant PR. 2019 The journal of physical chemistry. B Abstract HIV F99Y 256 260 PR 268 270 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. The F99Y mutation is shown via MD to decouple the closing of previously unrecognized distal pockets from substrate unbinding. 2019 The journal of physical chemistry. B Abstract HIV F99Y 4 8 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. The results indicate that the major energetic cost in flap opening is disengagement of the two flap-tip Ile50 residues from each other and is not affected by the F99Y mutation. 2019 The journal of physical chemistry. B Abstract HIV F99Y 162 166 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. To determine whether or not the F99Y mutation affects the energetic cost of wide flap opening, we use string method in collective variables to determine the minimum free-energy mechanism for wide flap opening in concert with distal pocket closing. 2019 The journal of physical chemistry. B Abstract HIV F99Y 32 36 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. A high-resolution X-ray crystal structure of PIE12 bound to the Q577R pocket revealed the loss of two hydrogen bonds, the repositioning of neighboring residues, and a small decrease in buried surface area. 2019 Retrovirology Abstract HIV Q577R 64 69 PI 45 47 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Surface plasmon resonance studies demonstrated substantial affinity loss between PIE12-trimer and the Q577R-mutated gp41 pocket. 2019 Retrovirology Abstract HIV Q577R 102 115 gp41 116 120 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The primary resistance mutation, Q577R/N/K, found in the conserved gp41 pocket, substantially decreases inhibitor affinity but also damages viral fitness, and candidate compensatory mutations in gp160 have been identified. 2019 Retrovirology Abstract HIV Q577K;Q577N;Q577R 33;33;33 42;42;42 gp41;gp160 67;195 71;200 31651864 HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. The most common drug resistance-associated mutations in protease inhibitors (PIs), NRTIs and NNRTIs were K20I/R, M184V/I and K103N/KN, respectively. 2019 Medicine Abstract HIV K103K;K103N;K20I;K20R;M184I;M184V 125;125;105;105;113;113 133;133;111;111;120;120 NNRTI;NRTI;PI;PR 93;83;77;56 99;88;80;64 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Conclusions: In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. 2019 Open forum infectious diseases Abstract HIV M184I;M184V 180;180 187;187 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Objective: The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. 2019 Open forum infectious diseases Abstract HIV M184I;M184V 29;29 36;36 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. 2019 Open forum infectious diseases Abstract HIV M184I;M184V 41;41 48;48 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35-4.59 and HR 1.66; 95% CI, 0.81-3.43, respectively). 2019 Open forum infectious diseases Abstract HIV M184I;M184V 76;76 83;83 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. The incidence of VF was 29.8 cases (11.2-79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4-21.8) in patients without documented M184V/I. 2019 Open forum infectious diseases Abstract HIV M184I;M184I;M184V;M184V 107;173;107;173 114;180;114;180 31678241 Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses. A significant trend for increasing prevalence of E138G mutation in CRF55_01B strains over time was observed (p < .001). 2020 Infection, genetics and evolution Abstract HIV E138G 49 54 31678241 Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses. Besides the natural presence of V179D and K103R/V179D in CRF65_cpx, the natural presence of V179E was found in CRF55_01B. 2020 Infection, genetics and evolution Abstract HIV K103R;V179D;V179D;V179E 42;48;32;92 47;53;37;97 31678241 Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses. In all but one of the 228 patients infected with CRF55_01B, NNRTI resistance mutation V179E was present and the combination of V179E and E138G was detected in 14 treatment-naive patients, with a rate of 6.2%. 2020 Infection, genetics and evolution Abstract HIV E138G;V179E;V179E 137;86;127 142;91;132 NNRTI 60 65 31678241 Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses. Most of the sequences containing E138G mutation scattered in the big CRF55_01B cluster, which indicated the rising prevalence of E138G was mainly due to multiple mutation events rather than local transmission clusters of a particular variant containing E138G mutation. 2020 Infection, genetics and evolution Abstract HIV E138G;E138G;E138G 33;129;253 38;134;258 31678241 Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses. Recently, our previous study has demonstrated the natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF65_cpx strains. 2020 Infection, genetics and evolution Abstract HIV K103R;V179D;V179D 84;90;74 89;95;79 NNRTI;NNRTI 184;136 190;171 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. Conversely, a mutation of lysine (K) to isoleucine (I) located in position six (K6I) of the envelope signal peptide was selected by chronic viruses and compared to TF (OR = 3.26, 95% CI (1.76-6.02), p = 0.0001). 2019 Viruses Abstract HIV K6I 80 83 Env 92 100 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The most prevalent聽Nucleoside聽Reverse Transcriptase Inhibitor (NRTI) mutations were聽M184V/I聽(67.3%),聽K219/Q/E聽(22.6%) and聽K65R聽(21.1%). 2019 Viruses Abstract HIV K219E;K219Q 101;101 109;109 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. This mutation of R to I (R841I) in the gp41 cytoplasmic tail (gp41CT), specifically in lentivirus lytic peptides segment 1 (LLP-1), is significantly enriched compared to chronic viruses (OR = 0.2, 95% CI (0.09, 0.44), p = 0.00001). 2019 Viruses Abstract HIV R841I 25 30 gp41 39 43 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. HIV-1 strains encoding Nef K94E and/or H116N display lower infectivity and replication capacity in the presence of SERINC5. 2019 Cell reports Abstract HIV H116N;K94E 39;27 44;31 Nef 23 26 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. We identify 18 Nef polymorphisms associated with differential function, including two CTL escape mutations that contribute to lower SERINC5 downregulation: K94E, driven by HLA-B*08, and H116N, driven by the protective allele HLA-B*57. 2019 Cell reports Abstract HIV H116N;K94E 186;156 191;160 Nef 15 18 31699949 HIV Drug Resistance after Failure of 6 Month First-line Therapy in a Hospital: A Case Series. The common NRTI mutations were M184VI and K65R, while NNRTI mutations were Y181CFGVY, K103N, A98AG, E138GQ and G190AGS. 2019 Acta medica Indonesiana Abstract HIV A98A;A98G;E138G;E138Q;G190A;G190G;G190S;K103N;K65R;M184I;M184V;Y181C;Y181F;Y181G;Y181V;Y181Y 93;93;100;100;111;111;111;86;42;31;31;75;75;75;75;75 98;98;106;106;118;118;118;91;46;37;37;84;84;84;84;84 NNRTI;NRTI 54;11 59;15 31702525 The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naive Children. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. 2019 Current HIV research Abstract HIV D67N;K103N;M184V;T215F;V179F 282;357;339;346;288 286;362;344;351;293 Pol 53 56 HIV infections 91 105 31709935 [Postmortem Molecular Epidemiology of HIV-1 Strains Isolated in Turkey]. Detected mutations were as follows: M41L, T215C, K65R, M184V, responsible for nucleoside reverse transcriptase inhibitor (NRTI) resistance; K103N, Y181C, G190A, responsible for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance; D30N, M46I, responsible for protease inhibitor (PI) resistance. 2019 Mikrobiyoloji bulteni Abstract HIV D30N;G190A;K103N;K65R;M184V;M41L;M46I;T215C;Y181C 244;154;140;49;55;36;250;42;147 248;159;145;53;60;40;254;47;152 NNRTI;NRTI;PR;NNRTI;NRTI;PI 177;78;272;225;122;292 213;110;280;230;126;294 31714421 Brief Report: Incidence of HIV in a Nationwide Cohort Receiving Pre-exposure Prophylaxis for HIV Prevention. Both were infected with viruses containing the M184V mutation. 2019 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 47 52 31718901 Evaluation of modified Vaccinia Ankara-based vaccines against foot-and-mouth disease serotype A24 in cattle. Because the FMDV wild-type 3C protease is detrimental to mammalian cells, one of four FMDV 3C protease variants were utilized: wild-type, or one of three previously reported mutants intended to dampen protease activity (C142T, C142L) or to increase specificity and thereby reduce adverse effects (L127P). 2020 Vaccine Abstract HIV C142L;C142T;L127P 227;220;297 232;225;302 PR;PR;PR 30;94;201 38;102;209 31718901 Evaluation of modified Vaccinia Ankara-based vaccines against foot-and-mouth disease serotype A24 in cattle. Two MVA-BN FMD constructs met the in vitro selection criteria to qualify for clinical studies: MVA-mBN360B (carrying a C142T mutant 3C protease and an HIV frameshift for reduced expression) and MVA-mBN386B (carrying a L127P mutant 3C protease). 2020 Vaccine Abstract HIV C142T;L127P 119;218 124;223 PR;PR 135;234 143;242 31735575 Fragment hopping-based discovery of novel sulfinylacetamide-diarylpyrimidines (DAPYs) as HIV-1 nonnucleoside reverse transcriptase inhibitors. Further optimization on the sulfur led to the sulfinylacetamide-DAPYs exhibiting improved anti-viral activity and a higher selectivity index especially toward the K103N mutant strain. 2020 European journal of medicinal chemistry Abstract HIV K103N 163 168 31735575 Fragment hopping-based discovery of novel sulfinylacetamide-diarylpyrimidines (DAPYs) as HIV-1 nonnucleoside reverse transcriptase inhibitors. The most potent compound 12a displayed EC50 values of 0.0249 muM against WT and 0.0104 muM against the K103N mutant strain, low cytotoxicity (CC50 > 221 muM) and a high selectivity index (SI WT > 8873, SI K103N > 21186). 2020 European journal of medicinal chemistry Abstract HIV K103N;K103N 103;205 108;210 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Nef and Nef-G2A co-immunoprecipitate with HDAC6, whereas the Nef-PPAA mutant showed a reduced interaction with the anti-HIV-1 enzyme. 2019 Frontiers in microbiology Abstract HIV G2A 12 15 Nef;Nef;Nef 0;8;61 3;11;64 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Nef appears to neutralize HDAC6 by an acidic/endosomal-lysosomal processing and does not need the downregulation function, since data obtained with the non-associated cell-surface Nef-G2A mutant - the cytoplasmic location of HDAC6 - together with studies with chemical inhibitors and other Nef mutants, point to this direction. 2019 Frontiers in microbiology Abstract HIV G2A 184 187 Nef;Nef;Nef 0;180;290 3;183;293 31741096 HIV-1 integrase drug-resistance mutations in Iranian treatment-experienced HIV-1-infected patients. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. 2020 Archives of virology Abstract HIV E138K;G140A;Q148R;S147G 69;76;94;83 74;81;99;88 INSTI 46 51 31745412 HIV Drug Resistance among Patients Failing Therapy at a Tertiary Center in Oman: A Case Record Review. M184V/I, K103N/S, and G190A/S/E were the most common mutations detected. 2019 Oman medical journal Abstract HIV G190A;G190E;G190S;K103N;K103S;M184I;M184V 22;22;22;9;9;0;0 31;31;31;16;16;7;7 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. M184V (8.4%, 20/239) and K103N (5.4%, 13/239) were the most prevalent mutations. 2019 PloS one Abstract HIV K103N;M184V 25;0 30;5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The largest TDR cluster of 53 persons with T215S was estimated to originate in the year 1992. 2019 Scientific reports Abstract HIV T215S 43 48 31761656 Heterocycle amide isosteres: An approach to overcoming resistance for HIV-1 integrase strand transfer inhibitors. A series of heterocyclic pyrimidinedione-based HIV-1 integrase inhibitors was prepared and screened for activity against purified integrase enzyme and/or viruses modified with the following mutations within integrase: Q148R, Q148H/G140S and N155H. 2020 Bioorganic & medicinal chemistry letters Abstract HIV G140S;N155H;Q148H;Q148R 231;241;225;218 236;246;230;223 IN;IN;IN 53;130;207 62;139;216 31764077 Genotypic resistance profiles of HIV-2-infected patients from Cape Verde failing first-line antiretroviral therapy. Resistance mutations were found in most patients (11/17; 64.7%) especially I82F (4/7; 57.1%) and M184V (10/17; 58.8%). 2020 AIDS (London, England) Abstract HIV I82F;M184V 75;97 79;102 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Among the Agno interactions, Rab11B, Importin and Crm-1 were first validated biochemically and further characterization was done for Crm-1, using a HIV-1 Rev-M10-like Agno mutant (L33D + E34L), revealing the critical roles of L33 and E34 residues in Crm-1 interaction. 2020 Virology Abstract HIV E34L;L33D 187;180 191;185 Rev 154 157 31767136 Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities. And also, it displayed potent activities against K103 N (EC50 = 0.077 muM), Y181C (EC50 = 0.11 muM), E138K (EC50 = 0.057 muM), and moderate activity against double mutants RES056 (EC50 = 8.7 muM). 2020 European journal of medicinal chemistry Abstract HIV E138K;K103N;Y181C 101;49;76 106;55;81 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. BACKGROUND: M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. 2020 The Journal of infectious diseases Abstract HIV M184I;M184V 12;12 19;19 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. 2020 The Journal of infectious diseases Abstract HIV M184I;M184V 114;114 121;121 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. CONCLUSIONS: Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. 2020 The Journal of infectious diseases Abstract HIV M184I;M184V 66;66 73;73 NNRTI 97 102 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen. 2020 The Journal of infectious diseases Abstract HIV M184I;M184V 33;33 40;40 NNRTI;NNRTI 158;111 163;146 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. In vitro, L74I compensated for defective replication of M184V-mutated virus. 2020 The Journal of infectious diseases Abstract HIV L74I;M184V 10;56 14;69 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). 2020 The Journal of infectious diseases Abstract HIV M184I;M184I;M184V;M184V;L74I 42;80;42;80;0 49;87;49;87;4 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. METHODS: We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. 2020 The Journal of infectious diseases Abstract HIV M184I;M184V 55;55 62;62 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. RESULTS: M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). 2020 The Journal of infectious diseases Abstract HIV M184I;M184V 9;9 16;16 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Virus load was similar in individuals with or without M184I/V (difference in log10 VL, 0.18; 95% confidence interval, .05-.31). 2020 The Journal of infectious diseases Abstract HIV M184I;M184V 54;54 61;61 31776272 HIV-1 Accessory Protein Vpr Interacts with REAF/RPRD2 To Mitigate Its Antiviral Activity. Using Vpr F34I and Q65R viral mutants, we show that nuclear localization and interaction with cullin 4A-DBB1 (DCAF1) E3 ubiquitin ligase are required for REAF degradation by Vpr. 2020 Journal of virology Abstract HIV F34I;Q65R 10;19 14;23 Vpr;Vpr 6;174 9;177 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. A total of 26 clusters containing PDR and a rapidly growing drug resistancerelated cluster containing the E138Q and V179D mutations were identified by genetic transmission network analysis. 2019 Current HIV research Abstract HIV E138Q;V179D 106;116 111;121 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. CONCLUSIONS: These findings identify the contributions of mutations of E560K/D/G in the highly conserved gp41 and highlight Env's high degree of plasticity for virus entry and inhibitor design. 2019 Retrovirology Abstract HIV E560D;E560G;E560K 71;71;71 80;80;80 gp41;Env 105;124 109;127 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560K mutation increased 6HB thermostability and resulted in resistance to N peptide inhibitors, but E560G or E560D as compensatory mutations destabilized the 6HB to reduce inhibitor binding and resulted in increased resistance to C peptide inhibitor, T20. 2019 Retrovirology Abstract HIV E560D;E560G;E560K 110;101;0 115;106;5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. RESULTS: The Glu560Lys/Asp/Gly (E560K/D/G) mutations in HR1 of gp41 that are selected under the pressure of N- and C-peptide inhibitors modified its molecular interactions with HR2 to change 6HB stability and peptide inhibitor binding. 2019 Retrovirology Abstract HIV E560D;E560D;E560G;E560G;E560K;E560K 13;32;13;32;13;32 30;41;30;41;30;41 gp41;Asp 63;23 67;26 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The E560K/D/G mutations changed its interactions with Gln650 (Q650) in HR2 to contribute to the resistance of peptide inhibitors. 2019 Retrovirology Abstract HIV E560D;E560G;E560K 4;4;4 13;13;13 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The molecular modeling analysis of E560K/D/G mutants suggested that position 560 might interact with the residues within two potentially flexible topological layer 1 and layer 2 in the gp120 inner domain to apparently affect the CD4 utilization. 2019 Retrovirology Abstract HIV E560D;E560G;E560K 35;35;35 44;44;44 gp120 185 190 31801862 Impact of Suboptimal APOBEC3G Neutralization on the Emergence of HIV Drug Resistance in Humanized Mice. Prior to treatment, variants with genotypic 3TC resistance (RT-M184I/V) were detected at low levels in over a third of all the animals. 2020 Journal of virology Abstract HIV M184I;M184V 63;63 70;70 RT 60 62 31818716 Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial. The OLA-guided therapy group had pre-ART peripheral blood mononuclear cells evaluated for drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) at codons Lys103Asn, Tyr181Cys, Gly190Ala, and to lamivudine at Met184Val, and when at least one drug-resistant codon was detected in a participant's pre-ART specimen, clinicians were directed to prescribe protease inhibitor-based second-line ART. 2020 The lancet. HIV Abstract HIV G190A;K103N;M184V;Y181C 196;174;228;185 205;183;237;194 NNRTI;NNRTI;PR 157;109;370 162;145;378 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Among all persons sharing DRMs, those sharing K103N were younger (aOR = 0.93, 95% CI 0.88-0.98, P = 0.003). 2020 The Journal of antimicrobial chemotherapy Abstract HIV K103N 46 51 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters). 2020 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K103S 110;110 117;117 31827312 Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data. The proposed methods are applied to analyze the ACTG 244 clinical trial to investigate the effects of antiretroviral treatment switching in HIV-infected patients before and after developing the T215Y antiretroviral drug resistance mutation. 2019 The Canadian journal of statistics Abstract HIV T215Y 194 199 HIV infections 140 152 31830799 HIV-1 Integrase Diversity and Resistance-Associated Mutations and Polymorphisms Among Integrase Strand Transfer Inhibitor-Naive HIV-1 Patients from Cameroon. A total of 18.9% (n = 7/37) of the sequences had RAMs, with only 5.4% (n = 2/37) having major RAMs (Y143R/C/D/G and P145S), against INSTIs. 2020 AIDS research and human retroviruses Abstract HIV P145S;Y143C;Y143D;Y143G;Y143R 116;100;100;100;100 121;111;111;111;111 INSTI 132 138 31830799 HIV-1 Integrase Diversity and Resistance-Associated Mutations and Polymorphisms Among Integrase Strand Transfer Inhibitor-Naive HIV-1 Patients from Cameroon. Accessory RAMs were present in 8.1% (n = 3/37) of the sequences, of which one sequence contained solely E157Q, and another Q95K. 2020 AIDS research and human retroviruses Abstract HIV E157Q;Q95K 104;123 109;127 31830799 HIV-1 Integrase Diversity and Resistance-Associated Mutations and Polymorphisms Among Integrase Strand Transfer Inhibitor-Naive HIV-1 Patients from Cameroon. One patient sequence had three accessory RAMs (G140E, E157Q, and G163R). 2020 AIDS research and human retroviruses Abstract HIV E157Q;G140E;G163R 54;47;65 59;52;70 31833849 Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. In one patient in each arm, an M184I and/or V RAM was detected. 2020 AIDS (London, England) Abstract HIV M184I 31 36 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. One-fifth (21%) had baseline resistance to at least one antiretroviral agent; the K103 N/S mutation was the most common mutation. 2019 BMC public health Abstract HIV K103N;K103S 82;82 90;90 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Here we provide a comprehensive kinetic and structural basis for inhibiting HIV-1 RT by (-)-FTC-TP and (-)-3TC-TP and drug resistance by M184V. 2019 Communications biology Abstract HIV M184V 137 142 RT 82 84 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. M184V RT displays greater (>200-fold) K d for the L-nucleotides and moderately higher (>9-fold) K d for the D-isomers compared to dCTP. 2019 Communications biology Abstract HIV M184V 0 5 RT 6 8 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The M184V RT structure illustrates how the mutation repositions the oxathiolane of (-)-FTC-TP and shifts its triphosphate into a non-productive conformation. 2019 Communications biology Abstract HIV M184V 4 9 RT 10 12 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Treatment with FTC or 3TC primarily selects for the HIV-1 RT M184V/I resistance mutations. 2019 Communications biology Abstract HIV M184I;M184V 61;61 68;68 RT 58 60 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. In in vitro tests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. 2019 Oxidative medicine and cellular longevity Abstract HIV G190S;K103N;K65R;M184V 141;135;68;73 146;140;72;78 Pol 91 101 31889319 Analyses of HIV-1 integrase gene sequences among treatment-naive patients in the Eastern Cape, South Africa. However, E157Q (2.1%), L74M/I (4.2%), and P142T (2.1%) were the observed accessory and polymorphic mutations. 2020 Journal of medical virology Abstract HIV E157Q;L74I;L74M;P142T 9;23;23;42 14;29;29;47 31889319 Analyses of HIV-1 integrase gene sequences among treatment-naive patients in the Eastern Cape, South Africa. Naturally occurring polymorphism observed were E11D, K14R, D25E, V31I, M50I, V72I, P90T, F100Y, L101I, T124A, T125A, K136Q, D167E, V201I, L234I, A265V, A269K, D278A, and S283G. 2020 Journal of medical virology Abstract HIV A265V;A269K;D167E;D25E;D278A;E11D;F100Y;K136Q;K14R;L101I;L234I;M50I;P90T;S283G;T124A;T125A;V201I;V31I;V72I 145;152;124;59;159;47;89;117;53;96;138;71;83;170;103;110;131;65;77 150;157;129;63;164;51;94;122;57;101;143;75;87;175;108;115;136;69;81 31914782 Prevalence of HIV-1 Drug-Resistance Genotypes Among Unique Recombinant Forms from Yunnan Province, China in 2016-2017. Mutations such as M184V/I (35.4%) in NRTIs and K103N/R/S/T (25.4%), V179D/E/T/Y (18.9%), G190A/E/R/S (13.8%), and Y181C (9.2%) in NNRTIs were common among the HIV-1 URF strains relative to other mutations. 2020 AIDS research and human retroviruses Abstract HIV G190A;G190E;G190R;G190S;K103N;K103R;K103S;K103T;M184I;M184V;V179D;V179E;V179T;V179Y;Y181C 89;89;89;89;47;47;47;47;18;18;68;68;68;68;114 100;100;100;100;58;58;58;58;25;25;79;79;79;79;119 NNRTI;NRTI 130;37 136;42 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. In a distal beta-sheet, mutations G73T and A71V coordinate with accessory mutations to bring about shifts that propagate throughout the subunit. 2020 The FEBS journal Abstract HIV A71V;G73T 43;34 47;38 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. In the protease hinge region, the N83D mutation eliminates a hydrogen bond connecting the hinge and core of the protease and increases disorder compared to highly resistant mutants PR with 17 mutations and PR with 20 mutations with similar hinge mutations. 2020 The FEBS journal Abstract HIV N83D 34 38 PR;PR;PR;PR 181;206;7;112 183;208;15;120 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS5B has 22 mutations including only one (I84V) in the inhibitor binding site; however, clinical inhibitors had poor inhibition of PRS5B activity with kinetic inhibition value (Ki ) values of 4-1000 nm or 18- to 8000-fold worse than for wild-type PR. 2020 The FEBS journal Abstract HIV I84V 43 47 PR 248 250 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). One NRTI-associated (M184V/I) and three NNRTI-associated (K103N/S, Y181C/I and G190A/S) mutations had high percentages in ART-naive and ART-treated individuals, and these mutations conferred high-level resistance to 3TC, EFV and/or NVP. 2020 EClinicalMedicine Abstract HIV G190A;G190S;K103N;K103S;M184I;M184V;Y181C;Y181I 79;79;58;58;21;21;67;67 86;86;65;65;28;28;74;74 NNRTI;NRTI 40;4 45;8 31923334 Altered-specificity mutants of the HIV Rev arginine-rich motif-RRE IIB interaction. A double mutant of Rev ARM, R35G-N40 V, uses an unknown strategy to recognize IIB. 2020 Journal of molecular recognition Abstract HIV R35G 28 32 Rev 19 22 31923334 Altered-specificity mutants of the HIV Rev arginine-rich motif-RRE IIB interaction. Affinity measurements in vitro and reporter assay measurements in vivo are consistent with the wild-type Rev ARM and R35G-N40V maintaining their recognition strategies when binding IIB mutants specific to wild-type Rev ARM and R35G-N40V, respectively. 2020 Journal of molecular recognition Abstract HIV N40V;N40V;R35G;R35G 122;232;117;227 126;236;121;231 Rev;Rev 105;215 108;218 31923334 Altered-specificity mutants of the HIV Rev arginine-rich motif-RRE IIB interaction. Here, isothermal titration calorimetry and gel shift assays show that the R35G-N40V-IIB interaction has high affinity and specificity in vitro and a larger unfavorable entropy change upon binding than that of wild-type Rev ARM-IIB. 2020 Journal of molecular recognition Abstract HIV N40V;R35G 79;74 83;78 Rev 219 222 31923334 Altered-specificity mutants of the HIV Rev arginine-rich motif-RRE IIB interaction. In stark contrast with the critical dependence of wild-type Rev on Arg35, Arg39, Asn40, and Arg44, mutational profiling shows R35G-N40V is highly mutable at positions 40 and 44 and dependent on Gly35, Arg38, Arg39, Arg42, and Arg43. 2020 Journal of molecular recognition Abstract HIV N40V;R35G 131;126 135;130 Rev 60 63 31923334 Altered-specificity mutants of the HIV Rev arginine-rich motif-RRE IIB interaction. Some single amino acid mutants of wild-type Rev ARM and R35G-N40V have enhanced specificity, recognizing mutant IIBs yet not wild-type IIB. 2020 Journal of molecular recognition Abstract HIV N40V;R35G 61;56 65;60 Rev 44 47 31926287 Retrospective study on the outcome of two-drug regimens based on dolutegravir plus one reverse transcriptase inhibitor in virologically-suppressed HIV-infected patients. One VF to DTG+RPV occurred because of historical resistance to RPV, accompanied by newly selected G140A and Q148R mutations. 2020 International journal of antimicrobial agents Abstract HIV G140A;Q148R 98;108 103;113 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 2020 HIV medicine Abstract HIV M184I;M184V 178;178 185;185 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. 2020 HIV medicine Abstract HIV M184I;M184V 58;58 65;65 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. 2020 HIV medicine Abstract HIV M184I;M184V 127;127 134;134 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. 2020 HIV medicine Abstract HIV M184I;M184V 42;42 49;49 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In contrast to the effect in the RGDA/Q112D background, the Q4R substitution diminished CA-CPSF6 interaction in an otherwise wild-type virus. 2020 AIDS research and human retroviruses Abstract HIV Q112D;Q4R 33;60 43;63 Capsid 88 90 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Notably, the Q4R substitution restored the CPSF6 interaction of the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Abstract HIV Q112D;Q4R 68;13 78;16 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Our genetic and structural analyses revealed that while either the Q4R or Q112D substitution impaired CA-CPSF6 interaction, the combination of these substitutions restored this interaction. 2020 AIDS research and human retroviruses Abstract HIV Q112D;Q4R 74;67 79;70 Capsid 102 104 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. The Q4R substitution conferred significant IFN-beta resistance to the RGDA/Q112D virus by affecting several properties of the virus, including the sensitivity to myxovirus resistance protein B (MxB), the kinetics of reverse transcription, and the initiation of uncoating. 2020 AIDS research and human retroviruses Abstract HIV Q112D;Q4R 70;4 80;7 RT 216 237 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. To better understand how the Q4R substitution modulated the CA-CPSF6 interaction, we generated a series of CA mutants harboring substitutions at the 4th and 112th residues. 2020 AIDS research and human retroviruses Abstract HIV Q4R 29 32 Capsid;Capsid 60;107 62;109 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We recently identified a Q4R mutation in CA after propagation of an interferon (IFN)-beta-hypersensitive CA mutant, RGDA/Q112D (H87R, A88G, P90D, P93A and Q112D) virus, in IFN-beta-treated cells. 2020 AIDS research and human retroviruses Abstract HIV A88G;H87R;P90D;P93A;Q112D;Q112D;Q4R 134;128;140;146;116;155;25 138;132;144;150;126;160;28 Capsid;Capsid 41;105 43;107 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Alanine scanning revealed decreased inhibition by the aptamer for mutants P420A, L422A and K424A. 2020 Nucleic acids research Abstract HIV K424A;L422A;P420A 91;81;74 96;86;79 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Mutations K103N, Y181C, G190A, M184V and K65R were detected by an oligonucleotide ligation assay (OLA) and confirmed by Sanger and next-generation sequencing (NGS). 2020 EClinicalMedicine Abstract HIV G190A;K103N;K65R;M184V;Y181C 24;10;41;31;17 29;15;45;36;22 31965175 Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2. In IN, 11 nonpolymorphic TSMs occurred in >=4 persons: Q91R, E92AQ, T97A, G140S, Y143G, Q148R, A153G, N155H, H156R, R231 5-amino acid insertions. 2020 The Journal of infectious diseases Abstract HIV A153G;E92A;E92Q;G140S;H156R;N155H;Q148R;Q91R;T97A;Y143G 95;61;61;74;109;102;88;55;68;81 100;66;66;79;114;107;93;59;72;86 IN 3 5 31965175 Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2. In PR, 12 nonpolymorphic TSMs occurred in >=11 persons: V33I, K45R, V47A, I50V, I54M, T56V, V62A, A73G, I82F, I84V, F85L, L90M. 2020 The Journal of infectious diseases Abstract HIV A73G;F85L;I50V;I54M;I82F;I84V;K45R;L90M;T56V;V33I;V47A;V62A 98;116;74;80;104;110;62;122;86;56;68;92 102;120;78;84;108;114;66;126;90;60;72;96 PR 3 5 31965175 Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2. In RT, 9 nonpolymorphic TSMs occurred in >=10 persons: K40R, A62V, K70R, Y115F, Q151M, M184VI, S215Y. 2020 The Journal of infectious diseases Abstract HIV A62V;K40R;K70R;M184I;M184V;Q151M;S215Y;Y115F 61;55;67;87;87;80;95;73 65;59;71;93;93;85;100;78 RT 3 5 31969438 Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice. However, it did not prevent transmission of Y181V HIV-1, which has 30-fold RPV resistance in the viruses used for this study. 2020 Journal of virology Abstract HIV Y181V 44 49 31969438 Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice. RPV LA significantly prevented vaginal transmission of WT HIV-1 and Y181C HIV-1, which is 3-fold resistant to RPV. 2020 Journal of virology Abstract HIV Y181C 68 73 31969438 Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice. Vaginal challenges of wild-type (WT), Y181C, and Y181V HIV-1 were performed in mice left untreated or after RPV PrEP. 2020 Journal of virology Abstract HIV Y181C;Y181V 38;49 43;54 31976534 Prevalence of doravirine-associated resistance mutations in HIV-1-infected antiretroviral-experienced patients from two large databases in France and Italy. In comparison, the prevalence of the common NNRTI mutations V90I, K101E/P, K103N/S, E138A/G/K/Q/R/S, Y181C/I/V and G190A/E/S/Q were higher (8.9%, 7.9%, 28.6%, 12.6%, 14.2% and 8.9%, respectively). 2020 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;E138S;G190A;G190E;G190Q;G190S;K101E;K101P;K103N;K103S;V90I;Y181C;Y181I;Y181V 84;84;84;84;84;84;115;115;115;115;66;66;75;75;60;101;101;101 99;99;99;99;99;99;126;126;126;126;73;73;82;82;64;110;110;110 NNRTI 44 49 31976534 Prevalence of doravirine-associated resistance mutations in HIV-1-infected antiretroviral-experienced patients from two large databases in France and Italy. RESULTS: The frequencies of doravirine-associated resistance mutations (total dataset versus NNRTI-failing patients) were: V106A/M, 0.8% versus 2.6%; V108I, 3.3% versus 9.2%; Y188L, 1.2% versus 2.6%; G190S, 0.3% versus 2.1%; F227C/L/V, 0.5% versus 1.8%; M230I/L, 2.8% versus 0%; L234I, 0.1% versus 0.5%; K103N + Y181C, 3.9% versus 3.9%; K103N + P225H, 2.9% versus 4.7%; and K103N + L100I, 1.7% versus 3.9%, with a significantly higher proportion of these mutations in the NNRTI-failing group (P < 0.05), except for M230I/L and K103N + Y181C. 2020 The Journal of antimicrobial chemotherapy Abstract HIV F227C;F227L;F227V;G190S;K103N;K103N;K103N;K103N;L100I;L234I;M230I;M230I;M230L;M230L;P225H;V106A;V106M;V108I;Y181C;Y181C;Y188L 225;225;225;200;304;337;374;527;382;279;254;515;254;515;345;123;123;150;312;535;175 234;234;234;205;309;342;379;532;387;284;261;522;261;522;350;130;130;155;317;540;180 NNRTI;NNRTI 93;472 98;477 31976534 Prevalence of doravirine-associated resistance mutations in HIV-1-infected antiretroviral-experienced patients from two large databases in France and Italy. The following mutations were considered as resistance mutations: V106A/M, V108I, Y188L, G190S, F227C/L/V, M230I/L, L234I, P236L, K103N + Y181C, K103N + P225H and K103N + L100I. 2020 The Journal of antimicrobial chemotherapy Abstract HIV F227C;F227L;F227V;G190S;K103N;K103N;K103N;L100I;L234I;M230I;M230L;P225H;P236L;V106A;V106M;V108I;Y181C;Y188L 95;95;95;88;144;162;129;170;115;106;106;152;122;65;65;74;137;81 104;104;104;93;149;167;134;175;120;113;113;157;127;72;72;79;142;86 31982483 Failure to bictegravir and development of resistance mutations in an antiretroviral-experienced patient. After several weeks, virological failure was confirmed with 4.01 HIV RNA Log copies/mL and R263K and M184V resistance mutations were detected. 2020 Antiviral research Abstract HIV M184V;R263K 101;91 106;96 31988104 Antiviral Activity of Tenofovir Alafenamide against HIV-1 with Thymidine Analog-Associated Mutations and M184V. Moreover, the presence of the M184V mutation increases TFV susceptibility during TDF- or TAF-based therapy. 2020 Antimicrobial agents and chemotherapy Abstract HIV M184V 30 35 31988104 Antiviral Activity of Tenofovir Alafenamide against HIV-1 with Thymidine Analog-Associated Mutations and M184V. The presence of M184V in TAM-containing HIV-1 SDMs (n = 48) significantly increased TAF sensitivity compared to SDMs without M184V (n = 48). 2020 Antimicrobial agents and chemotherapy Abstract HIV M184V;M184V 16;125 21;130 31988104 Antiviral Activity of Tenofovir Alafenamide against HIV-1 with Thymidine Analog-Associated Mutations and M184V. The susceptibilities to antiviral drugs of site-directed mutants (SDMs) and patient-derived mutants containing combinations of TAMs (M41L, D67N, K70R, L210W, T215Y, and K219Q) with or without the M184V mutation (TAMs+-M184V) were evaluated using either 5-day multicycle (MC; n = 110) or 2-day single-cycle (SC; n = 96) HIV assays. 2020 Antimicrobial agents and chemotherapy Abstract HIV D67N;K219Q;K70R;L210W;M184V;M184V;M41L;T215Y 139;169;145;151;196;212;133;158 143;174;149;156;201;223;137;163 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Glutamine-148 histidine (Q148H) and glycine-140 serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site. 2020 Science (New York, N.Y.) Abstract HIV G140S;G140S;Q148H;Q148H 36;56;0;25 54;61;23;30 INSTI;IN 125;91 130;100 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. The expanded chemical scaffolds of second-generation compounds mediate interactions with the protein backbone that are critical for antagonizing viruses containing the Q148H and G140S mutations. 2020 Science (New York, N.Y.) Abstract HIV G140S;Q148H 178;168 183;173 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Especially, 10i (EC50 = 0.43 muM) was more active to the L100I/K103N double-mutant strain as compared to both NVP (EC50 = 0.76 muM) and EFV (EC50 = 1.08 muM). 2020 European journal of medicinal chemistry Abstract HIV K103N;L100I 63;57 68;62 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. As expected, discriminatory DRMs such as K65R, L74I, and Y115F were noted in Tenofovir (TDF) containing regimens while the Thymidine Analogue Mutations (TAMs) L210W and T215 mutations were in Zidovudine (AZT)-based regimens. 2020 AIDS research and therapy Abstract HIV K65R;L210W;L74I;Y115F 41;157;47;57 45;164;51;62 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. The most prevalent Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutations were M184V/I (67.3%), K219/Q/E (22.6%) and K65R (21.1%). 2020 AIDS research and therapy Abstract HIV K65R;M184I;M184V 122;84;84 126;91;91 NRTI;NRTI 63;19 67;51 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. While K103N (50.8%) and G190A/S/E/G (29.1%) were the most prevalent Non-Nucleoside Reverse Transcriptase Inhibitor (NNTRI) mutations. 2020 AIDS research and therapy Abstract HIV G190A;G190E;G190G;G190S;K103N 24;24;24;24;6 35;35;35;35;11 NNRTI 68 104 32006797 Pharmacophore-fusing design of pyrimidine sulfonylacetanilides as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase. Compound 51 displayed exceptionally potent activity against WT virus (EC50 = 6 nM) and several mutant strains (L100I, EC50 = 8 nM, K103N, EC50 = 6 nM, Y181C, EC50 = 26 nM, Y188L, EC50 = 122 nM, E138K, EC50 = 26 nM). 2020 Bioorganic chemistry Abstract HIV E138K;K103N;L100I;Y181C;Y188L 194;131;111;151;172 199;136;116;156;177 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Neutralization activities targeting V2, CD4bs, V3 and gp120-gp41 interface only became detectable in week 350 plasma from macaques G1015R and G1020R using 25710 env mutants. 2020 Viruses Abstract HIV G1015R;G1020R 131;142 137;148 gp120;gp41;Env 54;60;161 59;64;164 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. When mapped with CAP45 env mutants, only V2 specificity was detected at week 217 and persisted until week 350 in G1015R. 2020 Viruses Abstract HIV G1015R 113 119 Env;Capsid 23;17 26;19 32030406 The algorithm used for the interpretation of doravirine transmitted drug resistance strongly influences clinical practice and guideline recommendations. Further genotype-phenotype studies are necessary to elucidate the role of V106I in doravirine resistance. 2020 The Journal of antimicrobial chemotherapy Abstract HIV V106I 74 79 32030406 The algorithm used for the interpretation of doravirine transmitted drug resistance strongly influences clinical practice and guideline recommendations. METHODS: We used the WHO 2009 list to investigate the prevalence of NNRTI, NRTI and PI TDR, in treatment-naive HIV-1-infected patients, adding mutations E138A/G/K/Q/R, V106I, V108I, V179L, G190Q, H221Y, F227C/L/V, M230IDR, L234I, P236L and Y318F in RT. 2020 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138G;E138K;E138Q;E138R;F227C;F227L;F227V;G190Q;H221Y;L234I;M230I;P236L;V106I;V108I;V179L;Y318F 153;153;153;153;153;203;203;203;189;196;223;214;230;168;175;182;240 166;166;166;166;166;212;212;212;194;201;228;221;235;173;180;187;245 NNRTI;NRTI;PI;RT 68;75;84;249 73;79;86;251 HIV infections 111 125 32030406 The algorithm used for the interpretation of doravirine transmitted drug resistance strongly influences clinical practice and guideline recommendations. V106I detection was not associated with any of the clinical, demographic or virological characteristics of the patients. 2020 The Journal of antimicrobial chemotherapy Abstract HIV V106I 0 5 32030406 The algorithm used for the interpretation of doravirine transmitted drug resistance strongly influences clinical practice and guideline recommendations. V106I, which was detected in 3.8% of the patients, was the main mutation driving these differences. 2020 The Journal of antimicrobial chemotherapy Abstract HIV V106I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. The Y143R/H/C substitutions were the most prevalent, followed by the N155H, and both Q148H/K and G140S/A in the same proportion. 2020 AIDS research and therapy Abstract HIV G140A;G140S;N155H;Q148H;Q148K;Y143C;Y143H;Y143R 97;97;69;85;85;4;4;4 104;104;74;92;92;13;13;13 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. Antiretroviral resistance was detected in 21.5% of 93 pol sequences analyzed, with the M184I/V and K103N mutations that confer high-level resistance to NRTI and NNRTI, respectively, being the most frequent mutations. 2020 PloS one Abstract HIV K103N;M184I;M184V 99;87;87 104;94;94 NNRTI;NRTI;Pol 161;152;54 166;156;57 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. However, the K103N mutant viruses were found only in the East. 2020 PloS one Abstract HIV K103N 13 18 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. BACKGROUND: The rate of S68G mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase has increased and is closely related to the K65R mutation among CRF01_AE-infected patients who failed treatment. 2020 BMC infectious diseases Abstract HIV K65R;S68G 151;24 155;28 RT 85 106 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. CONCLUSIONS: S68G may be a natural polymorphism and compensatory mutation of K65R selected by NRTIs in the CRF01_AE strain of HIV-1. 2020 BMC infectious diseases Abstract HIV K65R;S68G 77;13 81;17 NRTI 94 99 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In these three patients, there was no significant change detected in the half maximal inhibitory concentration for zidovudine, tenofovir, or lamivudine between the K65R and K65R/S68G mutations, as demonstrated by the phenotypic resistance assays. 2020 BMC infectious diseases Abstract HIV K65R;K65R;S68G 164;173;178 168;177;182 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. METHODS: The occurrence of S68G and K65R mutations was evaluated among HIV-1 of various subtypes in the global HIV Drug Resistance Database. 2020 BMC infectious diseases Abstract HIV K65R;S68G 36;27 40;31 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Next-generation sequencing revealed that the S68G mutation occurred following the K65R mutation in three of the four CRF01_AE-infected patients. 2020 BMC infectious diseases Abstract HIV K65R;S68G 82;45 86;49 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. RESULTS: The frequency of the S68G mutation increased by 1.4-9.7% in almost all HIV subtypes and circulating recombinant forms in treatment-experienced patients, except subtype F. 2020 BMC infectious diseases Abstract HIV S68G 30 34 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The impact of the S68G mutation on susceptibility to NRTI and replication fitness was analyzed using pseudovirus phenotypic resistance assays and growth competition assays, respectively. 2020 BMC infectious diseases Abstract HIV S68G 18 22 NRTI 53 57 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The S68G mutation often occurred in conjunction with the K65R mutation among RTI-treated patients, with frequencies ranging 21.1-61.7% in various subtypes. 2020 BMC infectious diseases Abstract HIV K65R;S68G 57;4 61;8 RT 77 80 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The temporal association of S68G and K65R mutations was analyzed through next-generation sequencing in four CRF01_AE-infected patients who failed treatment with tenofovir/lamivudine/efavirenz. 2020 BMC infectious diseases Abstract HIV K65R;S68G 37;28 41;32 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. This mutation does not affect susceptibility to NRTI; however, it improves the replication fitness of K65R mutants. 2020 BMC infectious diseases Abstract HIV K65R 102 106 NRTI 48 52 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. This study deciphers the role of the S68G mutation in the HIV reverse transcriptase of the CRF01_AE strain and provides new evidence for the interpretation of drug-resistant mutations in non-B subtypes of HIV-1. 2020 BMC infectious diseases Abstract HIV S68G 37 41 RT 62 83 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Virus stocks of the K65R and K65R/S68G mutations were mixed with 4:6, 1:1, and 9:1 and cultured for 13 days, the K65R/S68G mutants outgrew those of the K65R mutants irrespective of the input ratio. 2020 BMC infectious diseases Abstract HIV K65R;K65R;K65R;K65R;S68G;S68G 20;29;113;152;34;118 24;33;117;156;38;122 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. We aimed to explore the temporal association of S68G and K65R mutations and disclose the role of the former on susceptibility to nucleotide/nucleoside reverse transcriptase inhibitor (NRTI) and viral replication with the K65R double mutations among CRF01_AE-infected patients who failed treatment. 2020 BMC infectious diseases Abstract HIV K65R;K65R;S68G 57;221;48 61;225;52 NRTI;NRTI 140;184 172;188 32048186 Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV-1. Moreover, all of the diterpenoids shows significant inhibitions against T20-resistan HIV-1 strains, PNL4-3gp41(36G)V38E, N42S and pNL4-3gp41(36G)V38A, N42T. 2020 Natural products and bioprospecting Abstract HIV N42S;N42T;V38A;V38E 121;151;144;114 125;155;149;119 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Additionally, and at a lower level, protease inhibitor (PI)-resistance mutations, M46I, I54 V, V82A, L90 M, and I471 V, were also present in the sequences from antiretroviral therapy (ART)-experienced individuals. 2020 Medicine Abstract HIV I471V;I54V;L90M;M46I;V82A 112;88;101;82;95 118;93;106;86;99 PI;PR 56;36 58;44 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Major nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, M184I/V, D67N, T215F, and K70R/E were found. 2020 Medicine Abstract HIV D67N;K70E;K70R;M184I;M184V;T215F 87;104;104;78;78;93 91;110;110;85;85;98 NRTI;NRTI 50;6 54;38 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, K103N, Y181C, V90I, F227L, and V106A were also prevalent. 2020 Medicine Abstract HIV F227L;K103N;V106A;V90I;Y181C 97;77;108;91;84 102;82;113;95;89 NNRTI;NNRTI 48;0 53;36 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Two NRTI-associated drug resistance mutations (DRMs) (D67N and T69N) were present in sequences from 1 ART-naive individual.HIV-1 subtype CRF02_AG was most frequently detected in this study thus confirming earlier reports of dominance of this subtype in the West-African sub-region and Ghana in particular. 2020 Medicine Abstract HIV D67N;T69N 54;63 59;67 NRTI 4 8 32057044 Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T/L89M by molecular dynamics simulations and free energy analyses. Focusing on the wild type (WT) and G48T/L89M mutated forms of HIV-1 protease (HIV-1 PR) in complex with amprenavir (APV), indinavir (IDV), ritonavir (RTV), and nelfinavir (NFV), we have investigated the conformational dynamics and the resistance mechanism due to the G48T/L89M mutations by conducting a series of molecular dynamics (MD) simulations and free energy (MM-PBSA and solvated interaction energy (SIE)) analyses. 2020 Physical chemistry chemical physics Abstract HIV G48T;G48T;L89M;L89M 35;267;40;272 39;271;44;276 PR;PR 68;84 76;86 32057044 Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T/L89M by molecular dynamics simulations and free energy analyses. The simulation results indicate that alterations in the side-chains of G48T/L89M mutated residues cause the inner active site to increase in volume and induce more curling of the flap tips, which provide the main contributions to weaker binding of inhibitors to the HIV-1 PR. 2020 Physical chemistry chemical physics Abstract HIV G48T;L89M 71;76 75;80 PR 272 274 32065630 M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients. BACKGROUND: M184V/I NRTI resistance mutations can be selected by either lamivudine/emtricitabine or abacavir. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 12;12 19;19 NRTI 20 24 32065630 M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients. CONCLUSIONS: M184V/I as a unique NRTI resistance mutation, regardless of possible selection by regimens containing lamivudine/emtricitabine or abacavir, does not affect the virological response of well-controlled patients who switched to abacavir/lamivudine/dolutegravir for at least 12 months. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 13;13 20;20 NRTI 33 37 32065630 M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients. OBJECTIVES: We assessed the efficacy of abacavir/lamivudine/dolutegravir when used in HIV-infected pretreated patients with an undetectable VL who previously harboured M184V/I as a unique NRTI resistance mutation in a genotypic resistance test and had no resistance to integrase inhibitors. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 168;168 175;175 IN;NRTI 269;188 278;192 HIV infections 86 98 32065630 M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients. PATIENTS AND METHODS: A total of 154 patients with a fully suppressed HIV-1 plasma VL (<50 copies/mL) treated with tenofovir disoproxil fumarate/emtricitabine/boosted PI or abacavir/lamivudine/boosted PI who switched to an abacavir/lamivudine/dolutegravir regimen and had M184V/I as a unique NRTI resistance mutation in their therapeutic history were retrospectively analysed up to 12 months after the switch to abacavir/lamivudine/dolutegravir. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 272;272 279;279 NRTI;PI;PI 292;167;201 296;169;203 32065630 M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients. There are controversies about the use of abacavir/lamivudine/dolutegravir combinations in HIV-1-infected treatment-experienced patients with a fully suppressed HIV viral load (VL) and harbouring M184V/I. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 195;195 202;202 HIV infections 90 104 32071061 Discordance between Etravirine Phenotype and Genotype-Based Predicted Phenotype for Subtype C HIV-1 from First-Line Antiretroviral Therapy Failures in South Africa. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. 2020 Antimicrobial agents and chemotherapy Abstract HIV L100I;M230L;Y181C 10;27;17 15;32;22 32071061 Discordance between Etravirine Phenotype and Genotype-Based Predicted Phenotype for Subtype C HIV-1 from First-Line Antiretroviral Therapy Failures in South Africa. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. 2020 Antimicrobial agents and chemotherapy Abstract HIV K65R 32 36 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Additionally, we experimentally simulated previously reported ETV/3TC resistance for HBV using HIVY115F/F116Y/Q151M with F160M/M184V (L180M/M204V in HBV RT) substituted. 2020 Scientific reports Abstract HIV F116Y;Q151M;Y115F;F160M;M184V 104;110;98;121;127 109;115;103;126;132 RT 153 155 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Here, we show that human immunodeficiency virus type-1 (HIV-1) with HBV-associated amino acid substitutions Y115F/F116Y/Q151M in its RT (HIVY115F/F116Y/Q151M) is highly susceptible to ETV and 3TC. 2020 Scientific reports Abstract HIV F116Y;F116Y;Q151M;Q151M;Y115F;Y115F 114;146;120;152;140;108 119;151;125;157;145;113 RT 133 135 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Structural analysis of RTY115F/F116Y/Q151M/F160M/M184V:DNA:3TC-TP also demonstrated that the loosely bound 3TC-TP is misaligned at the active site to prevent a steric clash with the side chain gamma-methyl of Val184. 2020 Scientific reports Abstract HIV F116Y;F160M;M184V;Q151M;Y115F 31;43;49;37;25 36;48;54;42;30 RT 23 25 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We determined crystal structures for HIV-1 RTY115F/F116Y/Q151M:DNA complexed with 3TC-triphosphate (3TC-TP)/ETV-triphosphate (ETV-TP)/dCTP/dGTP. 2020 Scientific reports Abstract HIV F116Y;Q151M;Y115F 51;57;45 56;62;50 RT 43 45 32081778 High rates of tenofovir failure in a CRF01_AE-predominant HIV epidemic in the Philippines. Higher rates of NRTI, NNRTI, K65R tenofovir resistance, and multi-class resistance were found compared to those reported in literature. 2020 International journal of infectious diseases Abstract HIV K65R 29 33 NNRTI;NRTI 22;16 27;20 32096745 Analysis of Vpr Genetic Variations between Chinese Major Circulating Recombinants CRF01_AE and CRF07_BC. Of note, the R77Q mutation was found in both the most recently Chinese derived CRF07_BC and CRF01_AE Vpr. 2020 Current HIV research Abstract HIV R77Q 13 17 Vpr 101 104 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Deep sequencing of longitudinal plasma samples showed that L228R occurred simultaneously or followed the appearance of Y181C. 2020 BMC infectious diseases Abstract HIV L228R;Y181C 59;119 64;124 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Moreover, two unknown mutations (V75 L and L228R) increased by 19.0 and 11.9% respectively, and they were under positive selection (Ka/Ks > 1, log odds ratio [LOD] > 2) and were associated with several other DRMs (cKa/Ks > 1, LOD > 2). 2020 BMC infectious diseases Abstract HIV L228R;V75L 43;33 48;39 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The mutation rate at 14 sites increased significantly at TF time point compared to baseline, with the most common DRMs comprising G190S/C, K65R, K101E/N/Q, M184 V/I, and V179D/I/A/T/E, ranging from 66.7 to 45.2%. 2020 BMC infectious diseases Abstract HIV G190C;G190S;K101E;K101N;K101Q;K65R;M184I;M184V;V179A;V179D;V179E;V179I;V179T 130;130;145;145;145;139;156;156;170;170;170;170;170 137;137;154;154;154;143;164;164;183;183;183;183;183 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. 2020 The Journal of antimicrobial chemotherapy Abstract HIV L74I 150 154 IN 99 108 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L74I was detected in plasma samples at over 2% frequency in 40% (46/115). 2020 The Journal of antimicrobial chemotherapy Abstract HIV L74I 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). 2020 The Journal of antimicrobial chemotherapy Abstract HIV L74I 0 4 HIV infections 38 57 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The remaining 34 (73.9%) had L74I present at >20% frequency. 2020 The Journal of antimicrobial chemotherapy Abstract HIV L74I 29 33 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Two had Q148K minority variants and two had R263K (one of whom also had L74I). 2020 The Journal of antimicrobial chemotherapy Abstract HIV L74I;Q148K;R263K 72;8;44 76;13;49 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. 2020 The Journal of antimicrobial chemotherapy Abstract HIV L74I 48 52 IN;IN 38;84 47;93 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. 2020 The Journal of antimicrobial chemotherapy Abstract HIV L74I 80 84 IN 38 47 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3%-23.5% of samples). 2020 International journal of molecular sciences Abstract HIV A128T;E138D;E157Q;L74I;L74M;M50I;S119R;S230N;T97A 69;112;62;95;89;76;82;101;56 74;117;67;99;93;80;87;106;60 IN 0 9 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. 2020 International journal of molecular sciences Abstract HIV N155K;T66A 27;18 32;22 INSTI 6 12 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3'-PPT mutations. 2020 International journal of molecular sciences Abstract HIV I72V;I72V;L74M;L74M;T97A;T97A 28;53;33;39;44;58 32;57;37;43;48;62 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. Compound 10p exhibited the best activity against wild-type HIV-1 with an EC50 (50% HIV-1 replication inhibitory concentration) value of 0.027 microM, an acceptable CC50 (50% cytotoxic concentration) value of 36.4 microM, and selectivity index of 1361, with moderate activities against the single mutants (EC50: E138K, 0.17 microM; Y181C, 0.87 microM; K103N, 0.9 microM; L100I, 1.21 microM, respectively), and an IC50 value of 0.059 microM against the RT enzyme, which was six-fold higher than nevirapine (NVP). 2020 Molecules (Basel, Switzerland) Abstract HIV E138K;K103N;L100I;Y181C 311;351;370;331 316;356;375;336 RT 451 453 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. However, polymorphic accessory mutations associated with reduced susceptibility of integrase inhibitors were observed in low frequency; M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%). 2020 Ethiopian journal of health sciences Abstract HIV E157Q;E92G;G140A;G140C;G140S;M50I;S153G;S153Y;T97A 205;171;184;184;184;136;163;163;150 210;175;193;193;193;140;169;169;154 IN 83 92 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. M46I and I47V were the most common mutations for PIs, M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. 2020 PloS one Abstract HIV I47V;K103N;K103S;M184V;M46I 9;108;108;54;0 13;115;115;59;4 NNRTI;NRTI;PI 149;97;49 155;102;52 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. The SDRMs, D67N and D67E, belonged to the NRTIs class in two patients and K103N and V106A belonged to the NNRTIs class in three patients. 2020 PloS one Abstract HIV D67E;D67N;K103N;V106A 20;11;74;84 24;15;79;89 NNRTI;NRTI 106;42 112;47 32125378 Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). 2020 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138K;G140S;Q148H;Q148K;Q148R 73;73;63;52;52;52 80;80;68;61;61;61 IN;IN 0;34 3;36 32126792 Circulating HIV-1 Integrase Genotypes in Tanzania: Implication on the Introduction of Integrase Inhibitors-Based Antiretroviral Therapy Regimen. No major INSTI resistance mutations were found; however, accessory resistance mutations at positions T97A, E157Q, G163E/K, and 128A/T were detected in 5% of subjects. 2020 AIDS research and human retroviruses Abstract HIV E157Q;G163E;G163K;T97A 107;114;114;101 112;121;121;105 INSTI 9 14 32129987 Defective Strand-Displacement DNA Synthesis Due to Accumulation of Thymidine Analogue Resistance Mutations in HIV-2 Reverse Transcriptase. A mutant human immunodeficiency virus type 2 (HIV-2) RT (M41L/D67N/K70R/S215Y) with low strand displacement activity was identified after screening a panel of purified enzymes, including several antiretroviral drug-resistant HIV-1 and HIV-2 RTs. 2020 ACS infectious diseases Abstract HIV D67N;K70R;M41L;S215Y 62;67;57;72 66;71;61;77 RT;RT 241;53 244;55 32129987 Defective Strand-Displacement DNA Synthesis Due to Accumulation of Thymidine Analogue Resistance Mutations in HIV-2 Reverse Transcriptase. In contrast, mutants D67N/K70R/S215Y and M41L/D67N/K70R/S215Y were the most defective RTs in reactions carried out with nicked and gapped substrates. 2020 ACS infectious diseases Abstract HIV D67N;D67N;K70R;K70R;M41L;S215Y;S215Y 21;46;26;51;41;31;56 25;50;30;55;45;36;61 RT 86 89 32129987 Defective Strand-Displacement DNA Synthesis Due to Accumulation of Thymidine Analogue Resistance Mutations in HIV-2 Reverse Transcriptase. In HIV-1, resistance to zidovudine and other thymidine analogues is conferred by different combinations of M41L, D67N, K70R, L210W, T215F/Y, and K219E/Q (designated as thymidine analogue resistance-associated mutations (TAMs)). 2020 ACS infectious diseases Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 113;145;145;119;125;107;132;132 117;152;152;123;130;111;139;139 32129987 Defective Strand-Displacement DNA Synthesis Due to Accumulation of Thymidine Analogue Resistance Mutations in HIV-2 Reverse Transcriptase. Unlike in HIV-2, substitutions M41L/T215Y and D67N/K70R/T215Y/K219Q had no effect on the strand displacement activity of HIV-1BH10 RT. 2020 ACS infectious diseases Abstract HIV D67N;K219Q;K70R;M41L;T215Y;T215Y 46;62;51;31;36;56 50;67;55;35;41;61 RT 131 133 32129987 Defective Strand-Displacement DNA Synthesis Due to Accumulation of Thymidine Analogue Resistance Mutations in HIV-2 Reverse Transcriptase. We show that the strand displacement activity of HIV-2ROD mutants M41L/S215Y and D67N/K70R was only slightly reduced compared to the wild-type RT. 2020 ACS infectious diseases Abstract HIV D67N;K70R;M41L;S215Y 81;86;66;71 85;90;70;76 RT 143 145 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. The combinations N169D+K187E, N169D+S190N, and N169D+A389T resulted in MK1 neutralisation resistance close to that of #818. 2020 Pathogens (Basel, Switzerland) Abstract HIV A389T;K187E;N169D;N169D;N169D;S190N 53;23;17;30;47;36 58;28;22;35;52;41 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. The substitutions N169D and K187E, which added negative charges, and S190N in the V2 region of gp120 and A389T in V4, which created sites for N-glycan, conferred high neutralisation resistance. 2020 Pathogens (Basel, Switzerland) Abstract HIV A389T;K187E;N169D;S190N 105;28;18;69 110;33;23;74 gp120 95 100 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Therefore, N169D is the most important substitution for neutralisation resistance. 2020 Pathogens (Basel, Switzerland) Abstract HIV N169D 11 16 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. On the other hand, it was observed that those two compounds were less effective with EC50 values of 2.77 and 4.87 mumol/L for HIV-1A17 (K103N + Y181C). 2020 Acta pharmaceutica Sinica. B Abstract HIV K103N;Y181C 136;144 142;149 32141388 Presence of V72I, G123S and R127K Integrase Inhibitor polymorphisms could reduce ART effectiveness: a retrospective longitudinal study. Interestingly, patients with polymorphisms G123S and R127K had higher risk of failure at 24 W (respectively, relative risk - RR - 36, IQR 2.1-613, p = 0.01; RR 36, IQR 2.1-613, p = 0.01) and patients with V72I had an higher risk of failure both at 24 W (RR 6.52, IQR 1.29-32.9, p = 0.02) and 48 W (RR 21.1, IQR 1.07-414, p = 0.04).Conclusions: Our study showed that the presence of V72I, G123S and R127K polymorphisms could play a role in reducing InSTI effectiveness. 2020 HIV research & clinical practice Abstract HIV G123S;G123S;R127K;R127K;V72I;V72I 43;388;53;398;205;382 48;393;58;403;209;386 INSTI 448 453 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Interestingly, the second site suppressor capsid mutation R132T was able to rescue the uncoating kinetics of the E45A mutation, despite having a hyperstable capsid. 2020 Virology journal Abstract HIV E45A;R132T 113;58 117;63 Capsid;Capsid 42;157 48;163 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The capsid mutation A92E did not significantly alter uncoating kinetics. 2020 Virology journal Abstract HIV A92E 20 24 Capsid 4 10 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The E45A/R132T mutant virus specifically suggests that disrupted interactions with cellular factors, rather than capsid stability, is responsible for the delayed uncoating kinetics seen in E45A mutant virus. 2020 Virology journal Abstract HIV E45A;E45A;R132T 4;189;9 8;193;14 Capsid 113 119 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Viruses with capsid mutations N74D and E45A decreased the rate of uncoating in CHME3 cells, but did not alter reverse transcription. 2020 Virology journal Abstract HIV E45A;N74D 39;30 43;34 Capsid;RT 13;110 19;131 32154864 Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients. METHODS: Plasma samples from ART-naive or -experienced PLWH, including PI-experienced people, were sequenced and analysed for the presence of capsid variants identified during in vitro resistance selection: L56I, M66I, Q67H, K70N, N74D, N74S and T107N. 2020 The Journal of antimicrobial chemotherapy Abstract HIV K70N;L56I;M66I;N74D;N74S;Q67H;T107N 225;207;213;231;237;219;246 229;211;217;235;241;223;251 Capsid;PI 142;71 148;73 32158555 Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy. Thirty-five (47%) of 74 samples yielded a genotype result, and four (11%) had a major drug resistance mutation: two with K103N and two with V106M. 2020 Southern African journal of HIV medicine Abstract HIV K103N;V106M 121;140 126;145 32160290 Identification of gp120 polymorphisms in HIV-1 B subtype potentially associated with resistance to fostemsavir. A significantly higher prevalence in X4 viruses versus R5 viruses was found only for S375M (0.69% versus 3.93%, P = 0.009) and S375T (16.60% versus 22.11%, P = 0.030). 2020 The Journal of antimicrobial chemotherapy Abstract HIV S375M;S375T 85;127 90;132 32160290 Identification of gp120 polymorphisms in HIV-1 B subtype potentially associated with resistance to fostemsavir. Additionally, the M426R polymorphism had a prevalence of 16.32%. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M426R 18 23 32160290 Identification of gp120 polymorphisms in HIV-1 B subtype potentially associated with resistance to fostemsavir. RESULTS: The prevalence of fostemsavir resistance mutations was as follows: L116Q (0.05%), S375H/M/T (0.55%/1.35%/17.73%, the latter being far less relevant in determining resistance), M426L (7.56%), M434I (4.21%) and M475I (1.65%). 2020 The Journal of antimicrobial chemotherapy Abstract HIV L116Q;M426L;M434I;M475I;S375H;S375M;S375T 76;185;200;218;91;91;91 81;190;205;223;100;100;100 32160290 Identification of gp120 polymorphisms in HIV-1 B subtype potentially associated with resistance to fostemsavir. Some fostemsavirv resistance positions positively and significantly correlated with specific gp120 polymorphisms: S375T with I371V; S375M with L134W, I154V and I323T; M475I with K322A; and M426R with G167N, K192T and S195N. 2020 The Journal of antimicrobial chemotherapy Abstract HIV G167N;I154V;I323T;I371V;K192T;K322A;L134W;M426R;M475I;S195N;S375M;S375T 200;150;160;125;207;178;143;189;167;217;132;114 205;155;165;130;212;183;148;194;172;222;137;119 gp120 93 98 32163527 Doravirine: a new non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection. It has a novel resistance pathway so that it retains in vitro activity against clinically relevant NNRTI viral mutations K103N, Y181C and G190A. 2020 Drugs of today (Barcelona, Spain Abstract HIV G190A;K103N;Y181C 138;121;128 143;126;133 NNRTI 99 104 32168442 [Analysis of HIV-1 (Human immunodeficiency virus-1, Lentivirus, Orthoretrovirinae, Retroviridae) Nef protein polymorphism of variants circulating in the former USSR countries.] RESULTS AND DISCUSSION: The existence of noticeable differences in the prevalence of Nef natural polymorphisms (A32P, E38D, I43V, A54D, Q104K, H116N, Y120F, Y143F, V168M, H192T, V194R, R35Q, D108E, Y135F, E155K, E182M, R184K and F191L), some of which are characteristic mutations for variant A6, was shown. 2019 Voprosy virusologii Abstract HIV A32P;A54D;D108E;E155K;E182M;E38D;F191L;H116N;H192T;I43V;Q104K;R184K;R35Q;V168M;V194R;Y120F;Y135F;Y143F 112;130;191;205;212;118;229;143;171;124;136;219;185;164;178;150;198;157 116;134;196;210;217;122;234;148;176;128;141;224;189;169;183;155;203;162 Nef 85 88 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Importantly, doravirine remains active against K103N viruses in vitro, and limited clinical evidence suggests this to be the case in patients as well. 2020 Drugs in context Abstract HIV K103N 47 52 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Since K103N is by far the most prevalent (<70%) NNRTI substitution found in clinical practice, resistance against doravirine-based antiretroviral therapies is expected to be rare, even for treatment-experienced individuals. 2020 Drugs in context Abstract HIV K103N 6 11 NNRTI 48 53 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. M184V (62.04%), K103N (41.90%) and I54L (3.83%) were the most common observed mutations, respectively, in NRTI-, NNRTI- and PI-associated drug resistance. 2020 Virology journal Abstract HIV I54L;K103N;M184V 35;16;0 39;21;5 NNRTI;NRTI;PI 113;106;124 118;110;126 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Accordingly, depletion of TRIM5alphahu in CD4+ T cells rescues HIV-1 that fail to interact with CypA, such as HIV-1-P90A. 2020 Cell reports Abstract HIV P90A 116 120 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Disruption of CypA-capsid interactions fail to affect HIV-1-A92E/G94D infection, correlating with the loss of TRIM5alphahu binding to HIV-1-A92E/G94D cores. 2020 Cell reports Abstract HIV G94D;G94D;A92E;A92E 65;145;60;140 69;149;64;144 Capsid 19 25 32191306 Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals. Despite the great variability of gp120, the frequency of mutations was low overall and the predominant substitution was S375T, the role of which in reducing fostemsavir efficacy is less substantial. 2020 The Journal of antimicrobial chemotherapy Abstract HIV S375T 120 125 gp120 33 38 32191306 Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals. METHODS: Gp120 sequences from 409 subjects were retrospectively analysed and the presence of the L116P, A204D, S375H/M/T, M426L, M434I and M475I mutations was evaluated. 2020 The Journal of antimicrobial chemotherapy Abstract HIV A204D;L116P;M426L;M434I;M475I;S375H;S375M;S375T 104;97;122;129;139;111;111;111 109;102;127;134;144;120;120;120 gp120 9 14 32191306 Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals. RESULTS: The frequency of mutations was: S375T (13.2%); M426L (6.8%); M434I (2.9%); M475I (2.7%); S375H (1.0%)/M (0.8%) and L116P (0.31%). 2020 The Journal of antimicrobial chemotherapy Abstract HIV L116P;M426L;M434I;M475I;S375H;S375T 124;56;70;84;98;41 129;61;75;89;103;46 32191306 Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals. Statistically significant differences were found at positions 375 (R5/non-R5 strains and B/non-B subtypes) and 426 (B/non-B subtypes); post hoc analysis revealed that significance for position 375 was steered by S375T while for position 426 significance was governed by unusual substitutions, in particular M426R (B/non-B, P < 0.00001). 2020 The Journal of antimicrobial chemotherapy Abstract HIV M426R;S375T 307;212 312;217 32192810 Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity. Here, we relate V1V2 antigenicity to immunogenicity by comparing the immunogenicity profiles of wildtype and K155M immunogens in two mouse models. 2020 Vaccine Abstract HIV K155M 109 114 32192810 Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity. In a second model, we compared the effect of K155M on immunogenicity in the context of gp70 V1V2, gD V1V2 and gp120, examining the effects of scaffold, epitope-focusing and immunization regimen. 2020 Vaccine Abstract HIV K155M 45 50 gp120 110 115 32192810 Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity. K155M variants, especially in the context of a gp120 immunogen, resulted in more robust, durable and cross-reactive antibody responses than wildtype immunogens. 2020 Vaccine Abstract HIV K155M 0 5 gp120 47 52 32192810 Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity. Previously, we identified a V1V2 sequence variant (K155M) that results in enhanced recognition by cross-reactive antibodies recognizing the beta-strand conformation. 2020 Vaccine Abstract HIV K155M 51 56 32192810 Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity. Restriction of the beta-stranded V1V2 conformation in K155M immunogens may thus be associated with the induction of cross-reactive antibody responses thought to be required of a protective HIV-1 vaccine. 2020 Vaccine Abstract HIV K155M 54 59 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. Fifth, we determined the crystal structure of a 6-HB bearing the N126K mutation, which revealed the interhelical and intrahelical interactions underlying the increased thermostability. 2020 Viruses Abstract HIV N126K 65 70 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. First, we show that a single N126K mutation across several HIV-1 isolates conferred mild to moderate cross-resistances. 2020 Viruses Abstract HIV N126K 29 34 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. Fourth, the N126K mutation was verified to enhance the thermal stability of 6-HB conformation. 2020 Viruses Abstract HIV N126K 12 17 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. In this study, the functional and structural relevance of the N126K mutation has been characterized from multiple angles. 2020 Viruses Abstract HIV N126K 62 67 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. Second, the N126K mutation exerted different effects on Env-mediated HIV-1 entry and cell-cell fusion. 2020 Viruses Abstract HIV N126K 12 17 Env 56 59 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. The resistance profiles of various HIV-1 fusion inhibitors were previously characterized, and the secondary mutation N126K in the gp41 CHR was routinely identified during the in vitro and in vivo selections. 2020 Viruses Abstract HIV N126K 117 122 gp41 130 134 32197300 Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors. Third, the N126K mutation did not interfere with the expression and processing of viral Env glycoproteins, but it disrupted the Asn126-based glycosylation site in gp41. 2020 Viruses Abstract HIV N126K 11 16 gp41;Env 163;88 167;91 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. DESIGN: OLA-Simple probes to detect K65R, K103N/S, Y181C, M184V, and G190A were optimized for HIV Mexican sequences. 2020 AIDS (London, England) Abstract HIV G190A;K103N;K103S;K65R;M184V;Y181C 69;42;42;36;58;51 74;49;49;40;63;56 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Further, the protease mutants G40E and G40R are known to have decreased activity and were also subjected to MD simulations. 2020 Scientific reports Abstract HIV G40E;G40R 30;39 34;43 PR 13 21 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. Moreover, these two compounds had EC50 values of 0.06 and 0.08 muM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 muM). 2020 Molecules (Basel, Switzerland) Abstract HIV K103N 78 83 32253032 Thermal stressed human immunodeficiency virus type 1 nucleocapsid protein NCp7 maintains nucleic acid-binding activity. Moreover, both EDTA-treated and H23K + H44K double mutant of NCp7 inhibited first-strand cDNA synthesis, demonstrating that the NA-binding activity of NCp7 at high NC:NA ratios is independent on its zinc-fingers. 2020 Biochemical and biophysical research communications Abstract HIV H23K;H44K 32;39 36;43 NC;NC;NC 61;151;164 63;153;166 32259255 Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. 2020 The Journal of antimicrobial chemotherapy Abstract HIV K103N;Y181C 84;97 89;102 RT 80 82 32259255 Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial). Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). 2020 The Journal of antimicrobial chemotherapy Abstract HIV G190A;K101E;N155H;Q148R;Y143C;Y181C 69;40;143;130;117;54 74;45;148;135;122;59 IN;RT 106;5 115;7 32264923 Multidrug-resistant HIV viral rebound during early syphilis: a case report. A plasma RNA genotype resistance test revealed wild-type virus in the integrase region and protease region (PR), but extensive resistance in the reverse transcriptase (RT) region (M41L, E44D, D67N, K70R, M184V, L210W and T215Y). 2020 BMC infectious diseases Abstract HIV D67N;E44D;K70R;L210W;M184V;M41L;T215Y 192;186;198;211;204;180;221 196;190;202;216;209;184;226 RT;IN;PR;PR;RT 145;70;91;108;168 166;79;99;110;170 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Among the InSTI major RAM two (2.2%) sequences have Y143R and T97A mutations while one sample had T66I. 2020 Frontiers in microbiology Abstract HIV T66I;T97A;Y143R 98;62;52 102;66;57 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Of the 96 PR/RT sequences analyzed, M184V/I (52/96; 54%) had the most frequent RAM nucleoside reverse transcriptase inhibitor (NRTI). 2020 Frontiers in microbiology Abstract HIV M184I;M184V 36;36 43;43 NRTI;NRTI;PR;RT 127;83;10;13 131;115;12;15 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Protease inhibitor (PI) RAMs M46I and V82A were present in 12 (13%) of the sequences analyzed. 2020 Frontiers in microbiology Abstract HIV M46I;V82A 29;38 33;42 PI;PR 20;0 22;8 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The accessory RAM E157Q was identified in two (2.2%). 2020 Frontiers in microbiology Abstract HIV E157Q 18 23 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) RAM was K103N/S (40/96, 42%). 2020 Frontiers in microbiology Abstract HIV K103N;K103S 81;81 88;88 NNRTI;NNRTI 66;18 71;54 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Major PI resistance-associated mutations were identified at two sites including M46L (16.7% of subtype G/UG) and V82L (6.3% of CRF02_AG). 2020 PloS one Abstract HIV M46L;V82L 80;113 84;117 PI 6 8 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Minor PI resistance-associated mutations identified among subtype G/UG are L10V/I (8.3%) and K20I (100%) while L10V/I (50%), K20I (100%), L33F (6.3%) and N88D (6.3%) were identified among CRF02_AG. 2020 PloS one Abstract HIV K20I;K20I;L10I;L10I;L10V;L10V;L33F;N88D 93;125;75;111;75;111;138;154 97;129;81;117;81;117;142;158 PI 6 8 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Other polymorphisms found include; I13V/A, E35Q, M36I/L, N37D/S/E/H, R57K/G, L63T/P/S/Q, C67E/S, H69K/R, K70R, V82I and L89M in the range of 28.6% to 100% among the different subtypes. 2020 PloS one Abstract HIV C67E;C67S;E35Q;H69K;H69R;I13A;I13V;K70R;L63P;L63Q;L63S;L63T;L89M;M36I;M36L;N37D;N37E;N37H;N37S;R57G;R57K;V82I 89;89;43;97;97;35;35;105;77;77;77;77;120;49;49;57;57;57;57;69;69;111 95;95;47;103;103;41;41;109;87;87;87;87;124;55;55;67;67;67;67;75;75;115 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. The leading DRMs observed in the study were M184I/V (59.59%) against NRTIs and K103N (37.55%) against NNRTIs. 2020 BioMed research international Abstract HIV K103N;M184I;M184V 79;44;44 84;51;51 NNRTI;NRTI 102;69 108;74 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Through an unbiased screening approach, called HIV-CRISPR, we show that the CPSF6-binding deficient, N74D HIV-1 capsid mutant is sensitive to restriction mediated by human TRIM34, a close paralog of the well-characterized HIV restriction factor TRIM5alpha. 2020 PLoS pathogens Abstract HIV N74D 101 105 Capsid 112 118 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Through immunofluorescence studies, we show that TRIM34 and TRIM5alpha colocalize to cytoplasmic bodies and are more frequently observed to be associated with infecting N74D capsids than with WT HIV-1 capsids. 2020 PLoS pathogens Abstract HIV N74D 169 173 Capsid;Capsid 174;201 181;208 32294040 Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. 2020 Current HIV research Abstract HIV F214L;R211K;V245A;V245E 44;29;63;63 49;34;70;70 RT 105 107 32294040 Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. 2020 Current HIV research Abstract HIV E35D;G16E;I13I;I13V 50;41;33;33 54;45;39;39 32294040 Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance. 2020 Current HIV research Abstract HIV V179D;V179E 62;62 69;69 32294040 Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. 2020 Current HIV research Abstract HIV V179D;V179E 4;4 11;11 32300784 Characteristics of drug resistance in HIV-1 CRF55_01B from ART-experienced patients in Guangdong, China. Among DRMs, M184V (43.83%) was the most frequent NRTI DRM, followed by K65R (23.46%), and V179E (98.77%) was the most frequent NNRTI DRM, followed by K103N (47.53%) and Y181C (14.81%). 2020 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K65R;M184V;V179E;Y181C 150;71;12;90;169 155;75;17;95;174 NNRTI;NRTI 127;49 132;53 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Also, I54M and L90M may be responsible for asymmetric movement of the protease flaps. 2014 Discoveries (Craiova, Romania) Abstract HIV I54M;L90M 6;15 10;19 PR 70 78 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Our studies suggest I47V is involved in flap opening and the interaction between I47V and V32I tethers the flaps to the active site. 2014 Discoveries (Craiova, Romania) Abstract HIV I47V;I47V;V32I 20;81;90 24;85;94 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. We identify a novel structural role for the I47V, V32I, I54M and L90M major resistance mutations in flap opening and closure of MDR-PR isolates. 2014 Discoveries (Craiova, Romania) Abstract HIV I47V;I54M;L90M;V32I 44;56;65;50 48;60;69;54 PR 132 134 32321820 Impact of HLA-B*52:01-Driven Escape Mutations on Viral Replicative Capacity. A second HLA-B*52:01-associated mutation, K286R, flanking HLA-B*52:01-RI8, was also analyzed. 2020 Journal of virology Abstract HIV K286R 42 47 32321820 Impact of HLA-B*52:01-Driven Escape Mutations on Viral Replicative Capacity. Although selected in HLA-B*52:01-positive subjects often in combination with the V280X variants, this mutation did not act as a compensatory mutant but, indeed, further reduced VRC. 2020 Journal of virology Abstract HIV V280X 81 86 32321820 Impact of HLA-B*52:01-Driven Escape Mutations on Viral Replicative Capacity. Each of these variants reduced viral replicative capacity in C clade viruses, particularly the V280A variant (P < 0.0001 in both the C clade consensus and in the Indian study cohort consensus p24 Gag backbone), which was also associated with significantly higher absolute CD4 counts in the donors (median, 941.5 cells/mm3; P = 0.004). 2020 Journal of virology Abstract HIV V280A 95 100 Gag;p24 196;192 199;195 32321820 Impact of HLA-B*52:01-Driven Escape Mutations on Viral Replicative Capacity. We observed in HLA-B*52:01-positive individuals a higher frequency of V280T, V280S, and V280A variants within RI8 (P = 0.0001). 2020 Journal of virology Abstract HIV V280A;V280S;V280T 88;77;70 93;82;75 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. Two resistance-associated-mutations significantly associated to sub-subtype A6 samples: A62VRT and G190SRT. 2020 Viruses Abstract HIV A62V;G190S 88;99 94;106 32334191 Privileged scaffold inspired design of novel oxime-biphenyl-DAPYs in treatment of HIV-1. Compound 7d was found to be the most potent one against both wild type (EC50 = 12.1 nM) and E138K mutant strains (EC50 = 0.0270 microM). 2020 Bioorganic chemistry Abstract HIV E138K 92 97 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. 2020 BMC infectious diseases Abstract HIV K103R;V179D;V179D 60;66;50 65;71;55 NNRTI 112 118 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients. 2020 BMC infectious diseases Abstract HIV K103R;V179D 29;19 34;24 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. With one exception of V179E, the other 31 strains harbored V179D mutation. 2020 BMC infectious diseases Abstract HIV V179D;V179E 59;22 64;27 32360523 HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform. In the present study polymorphic mutation in the position of K20R, M36I, H69K, L89 M were properly reported in CRF35AD that is dominant in Iranian HIV patients. 2020 Microbial pathogenesis Abstract HIV H69K;K20R;M36I 73;61;67 77;65;71 32360523 HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform. NRTI and NNRTI associated dominant mutations were M184I/V and K103 N. 2020 Microbial pathogenesis Abstract HIV K103N 62 68 NNRTI;NRTI 9;0 14;4 32360523 HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform. NRTI and NNRTI associated dominant mutations were M184I/V and K103 N.High-level resistance to lamivudine (3 TC) and Emtricitabine (FTC) were detected in 34.3% of patients while 53.1% were resistant to Efavirenz (EFV) and Nevirapine (NVP). 2020 Microbial pathogenesis Abstract HIV M184I;M184V 50;50 57;57 NNRTI;NRTI 9;0 14;4 32360523 HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform. The Protease inhibitor (PI) minor and major mutations were not reported but more than 95% of samples had polymorphisms mutation in K20R, M36I, H69K, L89 M positions. 2020 Microbial pathogenesis Abstract HIV H69K;K20R;L89M;M36I 143;131;149;137 147;135;154;141 PI;PR 24;4 26;12 32360523 HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform. The secondary mutations were reported in positions of E157Q, S230 N, and T97A of integrase gene and four samples represent low-level resistance to integrase strand transfer inhibitor (INSTI). 2020 Microbial pathogenesis Abstract HIV E157Q;S230N;T97A 54;61;73 59;67;77 INSTI;IN;IN 184;81;147 189;90;156 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. The V179D/T was found to be very common in the China-Myanmar border region and was involved in half of the transmission clusters formed by HIV-1 drug-resistance strains in this region. 2020 Infection and drug resistance Abstract HIV V179D;V179T 4;4 11;11 32370607 First Detection of a Circulating Recombinant Form of HIV-1 CRF01_AE/08_BC (CRF105_0108) with Drug-Resistant Mutations in Sichuan, China. Three genetic sequences had drug-resistant mutations, E138Q and V179D, indicating that there were low resistance levels to efavirenz (EFV) and nevirapine (NVP) in Liangshan Yi Autonomous Prefecture. 2020 AIDS research and human retroviruses Abstract HIV E138Q;V179D 54;64 59;69 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. DRMs were common, with 28 of 179 (15.6%) specimens carrying DRMs, including the PR N88S and RT K103N mutations, which have been implicated in elevated resistance to antiretroviral drugs. 2020 Scientific reports Abstract HIV K103N;N88S 95;83 100;87 PR;RT 80;92 82;94 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Furthermore, 4 HIV-1 isolates (2.4%, 4/168) had surveillance drug-resistance mutation (SDRM), including 3 nonnucleosidereverse transcriptase inhibitors (NNRTI) SDRMs (1 K101E, 2 K103N) and 1 protease inhibitor (PI) SDRM (M46I). 2020 Scientific reports Abstract HIV M46I 221 225 NNRTI;PI;PR 153;211;191 158;213;199 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Change in free energy for the three mutants indicated different effects, while simulation analysis showed G140S to have the largest affect on protein stability and flexibility. 2020 PloS one Abstract HIV G140S 106 111 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Our findings suggest the G140S mutant has the strongest effect on the HIV-1C IN protein structure and Dolutegravir binding. 2020 PloS one Abstract HIV G140S 25 30 IN 77 79 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. This was further supported by weaker non-bonded pairwise interaction energy and binding free energy values between the drug DTG and E92Q, Y143R and G140S mutants suggesting reduced binding affinity, as indicated by interaction analysis in comparison to the WT. 2020 PloS one Abstract HIV E92Q;G140S;Y143R 132;148;138 136;153;143 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Three mutations known to be associated with Raltegravir, Elvitegravir and Dolutegravir resistance were selected; E92Q, G140S and Y143R, for molecular dynamics simulations. 2020 PloS one Abstract HIV E92Q;G140S;Y143R 113;119;129 117;124;134 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. 2020 Epidemiology and infection Abstract HIV G190A;K103N;K65R;Y188C;Y188F;Y188L 143;119;74;94;94;94 148;124;78;103;103;103 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. 2020 Epidemiology and infection Abstract HIV E138A;E138G;E138K;E138R;V179D;V179E;V179T 2;0;0;0;32;32;32 11;11;11;11;41;41;41 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Using Env chimeras and sequence analysis, we mapped this phenotype to a change Q563R, in the gp41 heptad repeat 1 (HR1) region. 2020 PLoS pathogens Abstract HIV Q563R 79 84 gp41;Env 93;6 97;9 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. We demonstrate that Q563R reduces viral infection by disrupting formation of the gp41 six-helix bundle required for virus-cell membrane fusion. 2020 PLoS pathogens Abstract HIV Q563R 20 25 gp41 81 85 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. We further demonstrate that the Q563R change increases HIV-1 sensitivity to broadly neutralizing antibodies (bNAbs) targeting the gp41 membrane-proximal external region (MPER). 2020 PLoS pathogens Abstract HIV Q563R 32 37 gp41 130 134 32404526 Therapeutic Efficacy and Resistance Selection of a Lipopeptide Fusion Inhibitor in Simian Immunodeficiency Virus-Infected Rhesus Macaques. Moreover, we showed that the resistance mutations greatly reduced the stability of diverse fusion inhibitors with the NHR site, and V562A or V562M in combination with E657G could significantly impair the functionality of viral envelopes (Envs) to mediate SIVmac239 infection and decrease the thermostability of viral six-helical bundle (6-HB) core structure. 2020 Journal of virology Abstract HIV E657G;V562A;V562M 167;132;141 172;137;146 Env;Env 227;238 236;242 32404526 Therapeutic Efficacy and Resistance Selection of a Lipopeptide Fusion Inhibitor in Simian Immunodeficiency Virus-Infected Rhesus Macaques. Sequence analyses revealed that a V562A or V562M mutation in the N-terminal heptad repeat (NHR) and a E657G mutation in the C-terminal heptad repeat (CHR) of SIV gp41 conferred high resistance to LP-52 and cross-resistance to the peptide drug T20 and two newly designed lipopeptides (LP-80 and LP-83). 2020 Journal of virology Abstract HIV E657G;V562A;V562M 102;34;43 107;39;48 gp41 162 166 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). Baseline next-generation sequencing detected lamivudine resistance mutations (M184V/I and/or K65R/E/N) over a 5% threshold in 15/21 (71 4%) and 3/20 (15%) of participants with and without history of lamivudine resistance, respectively. 2020 EBioMedicine Abstract HIV K65E;K65N;K65R;M184I;M184V 93;93;93;78;78 101;101;101;86;86 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. A plasma historical genotypic report (HGR) showing the presence of M184V/I was required for all participants and proviral HIV DNA analysis was conducted prior to enrolment. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 67;67 74;74 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. BACKGROUND: The M184V/I reverse transcriptase mutation, which confers major resistance to lamivudine and emtricitabine, is still quite frequent in people living with HIV. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 16;16 23;23 RT 24 45 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. CONCLUSIONS: Our results suggest that undetected M184V/I should be considered when switching virologically suppressed patients to new regimens, particularly two-drug lamivudine- or emtricitabine-containing combinations. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 49;49 56;56 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. Differential detection of M184V/I was not associated with timing differences between the HGR and proviral HIV DNA sampling, the overall duration of ART, or CD4 cell counts and HIV-1 viral load at baseline. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 26;26 33;33 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. METHODS: We analysed the detection of the M184V/I mutation in a prospective study and compared HIV historical genotypes (plasma) versus integrated HIV DNA (PBMCs) obtained via a validated commercial proviral HIV DNA assay. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 42;42 49;49 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. OBJECTIVES: To compare detectability of M184V/I in historical HIV-1 RNA analyses versus HIV-1 DNA sequencing. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 40;40 47;47 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. RESULTS: All 84 participants had evidence of M184V or M184I in their HGR (100%), whereas the mutation was detected in only 40/84 participants by proviral HIV DNA sequencing analysis (48%). 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 54;45 59;50 32413134 Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs. The underlying presence of the M184V/I mutation may undermine virological outcomes of ART, particularly in the context of proposed treatment with two-drug combinations that include drugs affected by M184V, such as lamivudine. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V;M184V 31;31;199 38;38;204 32430025 Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors. Finally, we show that L76V and N88S changes the hydrogen bond stability of these residues with residues D30/K45 and D30/T31/T74, respectively. 2020 Retrovirology Abstract HIV L76V;N88S 22;31 26;35 32430025 Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors. For the primary mutation L76V, however, the presence of a background mutation M46I in our analysis influences whether the unfavourable effect of L76V on inhibitor binding is sufficient to outweigh the accompanying reduction in catalytic activity of the protease. 2020 Retrovirology Abstract HIV L76V;L76V;M46I 25;145;78 29;149;82 PR 253 261 32430025 Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors. In this study, mutations N88S and L76V, along with three other resistance-associated mutations, M46I, I50L, and I84V, are analysed by means of molecular dynamics simulations to investigate their role in complexes of the protease with different inhibitors and in different background sequence contexts. 2020 Retrovirology Abstract HIV I50L;I84V;L76V;M46I;N88S 102;112;34;96;25 106;116;38;100;29 PR 220 228 32430025 Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors. N88S and L76V, do not only induce resistance to the currently administered drugs, but contrarily induce sensitivity towards other drugs. 2020 Retrovirology Abstract HIV L76V;N88S 9;0 13;4 32430025 Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors. RESULTS: Using these simulations for alchemical calculations to estimate the effects of mutations M46I, I50L, I84V, N88S, and L76V on binding free energies shows they are in general in line with the mutations' effect on [Formula: see text] values. 2020 Retrovirology Abstract HIV I50L;I84V;L76V;M46I;N88S 104;110;126;98;116 108;114;130;102;120 32430025 Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors. We show that distant site mutations L76V and N88S affect the hydrogen bond network in the protease's active site, which offers an explanation for the indirect effect of these mutations on inhibitor binding. 2020 Retrovirology Abstract HIV L76V;N88S 36;45 40;49 PR 90 98 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. M184V mutation associated with high level resistance to lamivudine and emtricitabine was detected in six out of seven patients. 2020 Antiviral chemistry & chemotherapy Abstract HIV M184V 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Pre-existing polymorphic integrase mutation (T97A) was detected in two patients. 2020 Antiviral chemistry & chemotherapy Abstract HIV T97A 45 49 IN 25 34 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Primary mutations (Y143C, N155H, T66I, G118R, E138K) conferring high level resistance to raltegravir were detected in only three patients. 2020 Antiviral chemistry & chemotherapy Abstract HIV E138K;G118R;N155H;T66I;Y143C 46;39;26;33;19 51;44;31;37;24 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. In one case, we detected an NRTI resistance mutation (M184V), in combination with multiple NNRTI resistance mutations. 2020 AIDS research and therapy Abstract HIV M184V 54 59 NNRTI;NRTI 91;28 96;32 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. The most common mutation was K103N (5.6%, 11/197), followed by Y181C (3.6%, 7/197). 2020 AIDS research and therapy Abstract HIV K103N;Y181C 29;63 34;68 32450199 Susceptibility to HIV-1 integrase strand transfer inhibitors (INSTIs) in highly treatment-experienced patients who failed an INSTI-based regimen. The primary INSTI resistance substitutions E138A/K, G140S, Y143C/H/R, Q148H and N155H were detected in 14 of 22 samples and were associated with resistance to one or more INSTIs, with G140S+Q148H present in 11 of 22 samples. 2020 International journal of antimicrobial agents Abstract HIV E138A;E138K;G140S;G140S;N155H;Q148H;Q148H;Y143C;Y143H;Y143R 43;43;184;52;80;190;70;59;59;59 50;50;189;57;85;195;75;68;68;68 INSTI;INSTI 12;171 17;177 32450199 Susceptibility to HIV-1 integrase strand transfer inhibitors (INSTIs) in highly treatment-experienced patients who failed an INSTI-based regimen. Two isolates contained L74M, E138K, G140S and Q148H, or L74M, T97A, S119T, E138K, G140S, Y143R and Q148H, and had high-level resistance to all INSTIs, including BIC and DTG. 2020 International journal of antimicrobial agents Abstract HIV E138K;E138K;G140S;G140S;L74M;L74M;Q148H;Q148H;S119T;T97A;Y143R 29;75;36;82;23;56;46;99;68;62;89 34;80;41;87;27;60;51;104;73;66;94 INSTI 143 149 32464638 In vitro susceptibility to fostemsavir is not affected by long-term exposure to antiviral therapy in MDR HIV-1-infected patients. Among 23/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). 2020 The Journal of antimicrobial chemotherapy Abstract HIV M426L;S375N 120;134 125;139 gp120 12 17 32475121 High Levels of Acquired HIV Drug Resistance Following Virological Nonsuppression in HIV-Infected Women from a High-Risk Cohort in Uganda. The mutation K103N was detected in 62.5% (30/48) of participants, 41.7% (20/48) had M184V/I, 14.6% had K65R, and 12.5% (6/48) had thymidine analog mutations (TAMs). 2020 AIDS research and human retroviruses Abstract HIV K103N;K65R;M184I;M184V 13;103;84;84 18;107;91;91 32493197 Application of Structure-based Methods to Analyze Resistance Mutations for Chemically Diverse Non-Nucleoside Reverse Transcriptase Inhibitors. Based on the determined resistance levels, we analyzed the models and used Molecular Dynamics (MD) to compare the interactions of MIV-150/doravirine with RT wild-type (WT) and RT (K101P). 2020 Current HIV research Abstract HIV K101P 180 185 RT;RT 154;176 156;178 32493197 Application of Structure-based Methods to Analyze Resistance Mutations for Chemically Diverse Non-Nucleoside Reverse Transcriptase Inhibitors. From MD, we found that key interactions were lost with RT (K101P), but were retained with doravirine. 2020 Current HIV research Abstract HIV K101P 59 64 RT 55 57 32493197 Application of Structure-based Methods to Analyze Resistance Mutations for Chemically Diverse Non-Nucleoside Reverse Transcriptase Inhibitors. The DeltaS + DeltaA values for K101P suggest that this mutation confers intermediate/high-level resistance to MIV-150, but remains susceptible to doravirine. 2020 Current HIV research Abstract HIV K101P 31 36 32493197 Application of Structure-based Methods to Analyze Resistance Mutations for Chemically Diverse Non-Nucleoside Reverse Transcriptase Inhibitors. To experimentally validate our findings, we conducted a fluorescence-based reverse transcription assay for MIV-150 with RT (WT) and RT (K101P). 2020 Current HIV research Abstract HIV K101P 136 141 RT;RT;RT 75;120;132 96;122;134 32500372 Retrospective analysis of HIV-1 drug resistance mutations in Suzhou, China from 2009 to 2014. Two of the mutations, M230L and L100I, which confer a high level of resistance efavirenz (EFV) and nevirapine (NVP) used as NNRTIs for first-line antiretroviral therapy (ART), were detected in this study. 2020 Virus genes Abstract HIV L100I;M230L 32;22 37;27 NNRTI 124 130 32522826 Diagnostic Accuracy of Pan-Degenerate Amplification and Adaptation Assay for HIV-1 Drug Resistance Mutation Analysis in Low- and Middle-Income Countries. In a cross-sectional study (June 2018 to September 2019), we evaluated the diagnostic accuracy of a simple and rapid HIVDR assay (the pan-degenerate amplification and adaptation [PANDAA] assay targeting the mutations K65R, K103NS, M184VI, Y181C, and G190A) compared to Sanger sequencing and next-generation sequencing (NGS). 2020 Journal of clinical microbiology Abstract HIV G190A;K103N;K103S;K65R;M184I;M184V;Y181C 250;223;223;217;231;231;239 255;229;229;221;237;237;244 32522826 Diagnostic Accuracy of Pan-Degenerate Amplification and Adaptation Assay for HIV-1 Drug Resistance Mutation Analysis in Low- and Middle-Income Countries. PANDAA showed strong agreement with Sanger sequencing for K65R, K103NS, M184VI, and G190A (kappa > 0.85) and substantial agreement for Y181C (kappa = 0.720). 2020 Journal of clinical microbiology Abstract HIV G190A;K103N;K103S;K65R;M184I;M184V;Y181C 84;64;64;58;72;72;135 89;70;70;62;78;78;140 32522853 Shedding-Resistant HIV-1 Envelope Glycoproteins Adopt Downstream Conformations That Remain Responsive to Conformation-Preferring Ligands. Shedding of gp120, known to severely complicate structural studies, can be prevented by using the uncleaved gp160JR-FL precursor with alterations in the protease cleavage site (R508S/R511S) or by introducing a disulfide bridge between gp120 and gp41 designated "SOS" (A501C/T605C). 2020 Journal of virology Abstract HIV A501C;R508S;R511S;T605C 268;177;183;274 273;182;188;279 PR;gp120;gp120;gp41 153;12;235;245 161;17;240;249 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Especially, compound 26 exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC50 ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR). 2020 Acta pharmaceutica Sinica. B Abstract HIV E138K;K103N;L100I;Y181C;Y188L 141;117;110;124;131 146;122;115;129;136 32539490 HIV-1 Genetic Diversity and High Prevalence of Pretreatment Drug Resistance in Tianjin, China. M64L (0.1%, 1/305) was the sole mutation found against protease inhibitors (PIs). 2020 AIDS research and human retroviruses Abstract HIV M64L 0 4 PI;PR 76;55 79;63 32539490 HIV-1 Genetic Diversity and High Prevalence of Pretreatment Drug Resistance in Tianjin, China. The most frequent mutation pattern against NNRTIs was V179D/E/T (6.9%, 21/305), with M184V (1.0%, 3/305) and K65R (1.0%, 3/305) against nucleoside RT inhibitors (NRTIs). 2020 AIDS research and human retroviruses Abstract HIV K65R;M184V;V179D;V179E;V179T 109;85;54;54;54 113;90;63;63;63 NNRTI;NRTI;RT 43;162;147 49;167;149 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. The HIV-1 capsid is the key determinant of MxB sensitivity and cofactor binding defective HIV-1 capsid mutants P90A (defective for cyclophilin A and Nup358 recruitment) and N74D (defective for CPSF6 recruitment) have reduced dependency on nuclear transport associated cofactors, altered integration targeting preferences and are not restricted by MxB expression. 2020 eLife Abstract HIV N74D;P90A 173;111 177;115 Capsid;Capsid 10;96 16;102 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. Half of the patients (n = 36/71, 51%) harboured genotypic drug resistance, with M184V (n = 18/36, 50%) and K103N (n = 16/36, 44%) being the most prevalent mutations. 2020 PloS one Abstract HIV K103N;M184V 107;80 112;85 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. These clonal variants harboured K95R, R286K and additional mutations in Gag. 2020 The Journal of antimicrobial chemotherapy Abstract HIV K95R;R286K 32;38 36;43 Gag 72 75 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. VESPA analyses identified K95R and R286K (P < 0.01) as signature mutations in Gag present at VF. 2020 The Journal of antimicrobial chemotherapy Abstract HIV K95R;R286K 26;35 30;40 Gag 78 81 32576136 Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study. The most common mutations in NNRTIs, NRTIs and PIs were K103N/KN (64.69%), M184V/MV/I (36.29%) and Q58E/QE (4.93%), respectively. 2020 BMC infectious diseases Abstract HIV K103K;K103N;M184I;M184M;M184V;Q58E;Q58Q 56;56;75;75;75;99;99 64;64;85;85;85;106;106 NNRTI;NRTI;PI 29;37;47 35;42;50 32598265 Application of Molecular Docking for the Development of Improved HIV-1 Reverse Transcriptase Inhibitors. Here, protein-ligand interactions and possible binding modes of novel compounds with the HIV-1 RT binding pocket (the wild-type as well as Y181C and K103N mutants) were obtained and discussed. 2021 Current computer-aided drug design Abstract HIV K103N;Y181C 149;139 154;144 RT 95 97 32601157 HIV-1 Integrase Inhibitors That Are Active against Drug-Resistant Integrase Mutants. Both were superior to DTG, as evidenced by the data obtained with the IN mutant T66I/L74M/E138K/S147G/Q148R/S230N, which was selected by CAB using an EVG-resistant lab strain. 2020 Antimicrobial agents and chemotherapy Abstract HIV E138K;L74M;Q148R;S147G;S230N;T66I 90;85;102;96;108;80 95;89;107;101;113;84 IN 70 72 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. INTERVENTIONS: Patient was initially rapidly started on a dolutegravir based regimen and changed to a protease inhibitor regimen once her genotype reported an S230R mutation. 2020 Medicine Abstract HIV S230R 159 164 PR 102 110 32631509 Discovery of potential dual-target prodrugs of HIV-1 reverse transcriptase and nucleocapsid protein 7. In addition, it showed moderate inhibitory potency (EC50 = 1.329 muM) against the HIV-1 K103N/Y181C double mutant strain (MT-4 cells). 2020 Bioorganic & medicinal chemistry letters Abstract HIV K103N;Y181C 88;94 93;99 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Here, we characterize the mode of action of N'-(2-hydroxy-benzylidene)-3,4,5-trihydroxybenzoylhydrazone (compound 13), an N-acylhydrazone derivative that inhibited viral replication (EC50 = 10 microM), while retaining full potency against the NNRTI-resistant double mutant K103N-Y181C virus. 2020 Viruses Abstract HIV K103N;Y181C 273;279 284;284 NNRTI 243 248 32642769 Persistent low-level viraemia in antiretroviral treatment-experienced patients is not linked to viral resistance or inadequate drug concentrations. The four virological failures were due to three ART interruptions and one incomplete adherence (selection of Y181C RAM). 2020 The Journal of antimicrobial chemotherapy Abstract HIV Y181C 109 114 32643196 Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site. Additional modifications to these compounds at the 4-position, computationally designed to compensate for the Y181C mutation, do not demonstrate improved potency. 2020 Protein science Abstract HIV Y181C 110 115 32643196 Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site. Comparison of 2-naphthyl phenyl ethers bound to Y181C RT reveal that compounds that interact with the invariant W229 are more capable of retaining efficacy against the resistance mutation. 2020 Protein science Abstract HIV Y181C 48 53 RT 54 56 32643196 Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site. Further biochemical and structural work demonstrated differences in potency against the Y181C mutation and binding mode of the compounds. 2020 Protein science Abstract HIV Y181C 88 93 32643196 Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site. One class of developed compounds are the 2-naphthyl phenyl ethers, showing promising efficacy against the Y181C RT mutation. 2020 Protein science Abstract HIV Y181C 106 111 RT 112 114 32653726 High rate of antimicrobial resistance and multiple mutations in the dihydrofolate reductase gene among Streptococcus pneumoniae isolated from HIV-infected adults in a community setting in Tanzania. Co-trimoxazole-resistant isolates carried from 1 to 11 different mutations in the dihydrofolate reductase (DHFR) gene, most commonly Ile100Leu (100%), Glu20Asp (91.8%), Glu94Asp (61.2%), Leu135Phe (57.1%), His26Tyr (53.1%), Asp92Ala (53.1%) and His120Gln (53.1%). 2020 Journal of global antimicrobial resistance Abstract HIV D92A;E20D;E94D;H120Q;H26Y;I100L;L135F 224;151;169;245;206;133;187 232;159;177;254;214;142;196 Asp 224 227 32655148 Impact of Pre-antiretroviral Therapy CD4 Counts on Drug Resistance and Treatment Failure: A Systematic Review. Most frequent resistance mutations included the M184I/V for the nucleoside reverse-transcriptase inhibitors (NRTIs), K103N, and Y181 for the non-NRTIs (NNRTIs), and L90M for the Protease inhibitors. 2020 AIDS reviews Abstract HIV K103N;L90M;M184I;M184V 117;165;48;48 122;169;55;55 NRTI;NNRTI;PR;NNRTI;NRTI 64;141;178;152;109 96;150;186;158;114 32663847 Near Real-Time Identification of Recent Human Immunodeficiency Virus Transmissions, Transmitted Drug Resistance Mutations, and Transmission Networks by Multiplexed Primer ID-Next-Generation Sequencing in North Carolina. The reverse-transcriptase region K103N was the most commonly detected DRM (prevalence, approximately 15%). 2021 The Journal of infectious diseases Abstract HIV K103N 33 38 RT 4 25 32669335 A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. Here, we report a rare leucine-to-phenylalanine escape mutation (L184F) at the base of hypervariable loop 2 (population frequency of 0.0045%) in a 9-month-old perinatally HIV-1-infected infant broad neutralizer. 2020 Journal of virology Abstract HIV L184F 65 70 HIV infections 171 185 32669335 A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. In conclusion, we report a naturally selected viral mutation, L184F, that influenced a change in the conformation of the Env trimer apex as a mechanism of escape from contemporaneous plasma V2 apex-targeted nAbs. 2020 Journal of virology Abstract HIV L184F 62 67 Env 121 124 32669335 A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. The L184F amino acid change led to the acquisition of a relatively open trimeric conformation, often associated with tier 1 HIV-1 isolates and increased susceptibility to neutralization by polyclonal plasma antibodies of weak neutralizers. 2020 Journal of virology Abstract HIV L184F 4 9 32669335 A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. The L184F mutation altered the trimer conformation by modulating intramolecular interactions stabilizing the trimer apex and led to viral escape from autologous plasma bnAbs and known N160 glycan-targeted bnAbs. 2020 Journal of virology Abstract HIV L184F 4 9 32669335 A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. While there was no impact of the L184F mutation on free virus transmission, a reduction in cell-to-cell transmission was observed. 2020 Journal of virology Abstract HIV L184F 33 38 32675772 Brief Report: Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and SWORD-2 Randomized Clinical Trials. Participants with screening HIV-1 RNA <50 copies/mL for >=6 months; no prior virologic failure; and no documented resistance-associated major protease inhibitor, integrase inhibitor, nucleoside reverse transcriptase inhibitor (NRTI), or non-NRTI mutations or integrase resistance-associated substitution R263K were randomly assigned 1:1 to switch to once-daily dolutegravir 50 mg plus rilpivirine 25 mg on day 1 (early-switch group) or to continue their current antiretroviral regimen and, if virologically suppressed at week 48, switch to dolutegravir plus rilpivirine at week 52 (late-switch group) until week 148. 2020 Journal of acquired immune deficiency syndromes (1999) Abstract HIV R263K 304 309 NRTI;IN;IN;NNRTI;PR;NRTI 183;162;259;237;142;227 215;171;268;245;150;231 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. Fifteen (15) PDR mutations were found among four patients the urban settings [6 resistance mutations to NRTIs:[M41L (2), E44D (1), K65R (1), K70E (1), M184V/I (2), K219R (1)] and 6 resistance mutations to NNRTIs: K103N (1), E138A/G (2), V179E (1), M230L (1), K238T (1), P225H (1)] against two (02) mutations found in two patients in the rural setting[2 resistant mutations to NNRTIs: E138A (1) and Y188H (1)]. 2020 PloS one Abstract HIV E138A;E138A;E138G;E44D;K103N;K219R;K238T;K65R;K70E;M184I;M184V;M230L;M41L;P225H;V179E;Y188H 224;384;224;121;213;164;259;131;141;151;151;248;111;270;237;398 231;389;231;125;218;169;264;135;145;158;158;253;115;275;242;403 NNRTI;NNRTI;NRTI 205;376;104 211;382;109 32694410 Tenofovir resistance in early and long-term treated patients on first-line antiretroviral therapy in eight low-income and middle-income countries. Overall, tenofovir resistance was mainly due to K65R or K70E/G/N/A/S/T/Y115F mutations (79%) but also due to thymidine analogue mutations (21%) which arise from exposure to thymidine analogues but causing cross-resistance to TDF. 2020 AIDS (London, England) Abstract HIV K65R;K70A;K70E;K70G;K70N;K70S;K70T;Y115F 48;56;56;56;56;56;56;72 52;72;72;72;72;72;72;76 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. Sequencing confirmed a dominant wild type at month one with dual therapy resistance patterns emerging by month three (M184V and K65R mutations), which is suggestive of protracted PrEP use during an undetected HIV infection. 2020 BMC infectious diseases Abstract HIV K65R;M184V 128;118 132;124 HIV infections 209 222 32701823 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) From Dolutegravir (DTG)+F/TAF or DTG+F/Tenofovir Disoproxil Fumarate (TDF) in the Presence of Pre-existing NRTI Resistance. M184V/I was present in 14% (81/565). 2020 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 0;0 7;7 32701823 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) From Dolutegravir (DTG)+F/TAF or DTG+F/Tenofovir Disoproxil Fumarate (TDF) in the Presence of Pre-existing NRTI Resistance. RESULTS: In total, 83% (470/565) of participants had baseline genotypic data available with NRTI-R detected in 24% (138/565), including 5% (30/565) with K65R/E/N or >=3 thymidine analog mutations and 19% (108/565) with other NRTI-R mutations. 2020 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K65E;K65N;K65R 153;153;153 161;161;161 NRTI;NRTI 92;225 96;229 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. CONCLUSION: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. 2020 Virology journal Abstract HIV E138A;K65R 62;72 67;76 NNRTI;NRTI;RT 134;145;84 140;149;86 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. 2020 Virology journal Abstract HIV E138A;K65R 120;157 125;161 32712537 Bioisosterism-based design and enantiomeric profiling of chiral hydroxyl-substituted biphenyl-diarylpyrimidine nonnucleoside HIV-1 reverse transcriptase inhibitors. Among all the chiral derivatives, (S)-(-)-12a showed the best potency with the antiviral activities against wild-type (WT) and single mutant strains (L100I, K103 N, Y181C, E138K; especially Y188L), and RT enzyme in the low nanomolar concentration range. 2020 European journal of medicinal chemistry Abstract HIV E138K;K103N;L100I;Y181C;Y188L 172;157;150;165;190 177;163;155;170;195 RT 202 204 32712537 Bioisosterism-based design and enantiomeric profiling of chiral hydroxyl-substituted biphenyl-diarylpyrimidine nonnucleoside HIV-1 reverse transcriptase inhibitors. Toward double mutant virus strains (F227L + V106A, RES056), (S)-(-)-12a possessed submicromolar antiviral activities. 2020 European journal of medicinal chemistry Abstract HIV F227L;V106A 36;44 42;49 32715952 Pooled resistance analyses of darunavir once-daily regimens and formulations across 10 clinical studies of treatment-naive and treatment-experienced patients with human immunodeficiency virus-1 infection. Among 3317 patients using nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs; mostly emtricitabine and tenofovir), 13 (0.4%) had >=1 N(t)RTI RAM (10 with M184I/V). 2020 HIV research & clinical practice Abstract HIV M184I;M184V 160;160 167;167 NRTI;NRTI;NRTI 139;74;26 146;82;61 32715952 Pooled resistance analyses of darunavir once-daily regimens and formulations across 10 clinical studies of treatment-naive and treatment-experienced patients with human immunodeficiency virus-1 infection. Among patients receiving D/C/F/TAF (n = 1949), none had post-baseline darunavir, primary PI, or tenofovir RAMs; only two (0.1%) patients developed an emtricitabine RAM, M184V/I. 2020 HIV research & clinical practice Abstract HIV M184I;M184V 169;169 176;176 PI 89 91 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. To further investigate the connection between limited peptide presentation and robust T cell responses, we used CRISPR/Cas9 to generate mice with a point mutation (W97R) in the peptide-binding groove of Ld that results in broader peptide binding. 2020 Frontiers in immunology Abstract HIV W97R 164 168 Capsid 119 121 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. We investigated the effect of this Ld W97R mutation on another robust Ld-restricted response against the IE1 peptide during Murine Cytomegalovirus (MCMV) infection. 2020 Frontiers in immunology Abstract HIV W97R 38 42 32737511 Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV. CONCLUSIONS: Among virally suppressed PLWH, EVG/C/FTC/TAF is effective in maintaining viral suppression at Week 48 despite archived M184V/I mutation with or without TAMs. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 132;132 139;139 32737511 Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV. OBJECTIVES: Real-world experience regarding the effectiveness of co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/C/FTC/TAF) as a switch regimen is sparse among people living with HIV (PLWH) harbouring the M184V/I mutation with or without thymidine analogue-associated mutations (TAMs). 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 242;242 249;249 32737511 Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV. Patients with archived M184V/I mutation (case patients) were matched to controls without M184V/I mutation at a 1:4 ratio. 2020 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184I;M184V;M184V 23;89;23;89 30;96;30;96 32737511 Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV. RESULTS: Overall, 100 case patients with the M184V/I mutation were identified, including 6 (6.0%) with K65R and 13 (13.0%) with at least one TAM, and were matched to 400 controls in terms of gender, age (mean = 40.3 versus 39.7 years) and cumulative exposure duration to tenofovir disoproxil fumarate (median = 146 versus 143 weeks). 2020 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184I;M184V 103;45;45 107;52;52 32737511 Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV. The presence of the K65R mutation or TAMs was not associated with virological non-response. 2020 The Journal of antimicrobial chemotherapy Abstract HIV K65R 20 24 32747359 Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase. Clinically relevant combinations of TAMs, such as M41L/T215Y or D67N/K70R/T215F/K219Q, enhance the ATP-mediated excision of AZT monophosphate (AZTMP) from the 3' end of the primer, allowing DNA synthesis to continue. 2020 Antimicrobial agents and chemotherapy Abstract HIV D67N;K219Q;K70R;M41L;T215F;T215Y 64;80;69;50;74;55 68;85;73;54;79;60 32747359 Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase. In HIV-1, development of resistance to AZT (3'-azido-3'-deoxythymidine) is mediated by the acquisition of thymidine analogue resistance mutations (TAMs) (i.e., M41L, D67N, K70R, L210W, T215F/Y, and K219E/Q) in the viral reverse transcriptase (RT). 2020 Antimicrobial agents and chemotherapy Abstract HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 166;198;198;172;178;160;185;185 170;205;205;176;183;164;192;192 RT;RT 220;243 241;245 32747359 Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase. RNase H inactivation by introducing the active-site mutation E478Q led to the loss of the inhibitory effect shown by NCp9. 2020 Antimicrobial agents and chemotherapy Abstract HIV E478Q 61 66 NC 117 119 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Additionally, we confirmed that the L74I mutation was selected at the early stage of the epidemic and subsequently spread as a founder effect in Russia. 2020 Viruses Abstract HIV L74I 36 40 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Analysis of the genetic barriers determined two positions in which subtype A (A1 and A6) showed a higher genetic barrier (G140C and V151I) compared with subtype B, and one position in which subtypes A1 and B displayed a higher genetic barrier (L74M and L74I) than sub-subtype A6. 2020 Viruses Abstract HIV G140C;L74I;L74M;V151I 122;253;244;132 128;257;249;137 32761071 Human Immunodeficiency Virus (HIV) Drug Resistance, Phylogenetic Analysis, and Superinfection Among Men Who Have Sex with Men and Transgender Women in Sub-Saharan Africa: HIV Prevention Trials Network (HPTN) 075 Study. Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. 2021 Clinical infectious diseases Abstract HIV K103N;M184I;M184V 127;137;137 132;144;144 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%). 2020 PloS one Abstract HIV D67N;K219E;K219Q;K70E;K70N;K70Q;K70R;K70T;T215I;T215T 51;35;35;17;17;17;17;17;68;68 55;41;41;25;25;25;25;25;74;74 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Emergence of these mutations including the NNRTI associated mutations (Y181C and Y188C) may compromise future second- and third-line regimens in the absence of routine HIVDR testing. 2020 PloS one Abstract HIV Y181C;Y188C 71;81 77;86 NNRTI 43 48 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP). 2020 PloS one Abstract HIV K103N 50 55 NNRTI 16 21 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The mutation M184V which confers resistance to NRTI drugs of lamivudine (3TC) and emtricitabine (FTC) was the most common (81%) among NRTI associated mutations followed by K65R (34.5%) which is associated with both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) resistance. 2020 PloS one Abstract HIV K65R;M184V 172;13 176;18 NRTI;NRTI 47;134 51;138 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine. 2020 PloS one Abstract HIV V106A;Y181C;Y188C 64;108;90 69;113;95 NNRTI 48 53 32819562 HIV-1 Nef promotes ubiquitination and proteasomal degradation of p53 tumor suppressor protein by using E6AP. However, Nef mediated reduction in p53 induced apoptosis of H1299 cells was restored when Nef was co-expressed with E6AP-C843A. 2020 Biochemical and biophysical research communications Abstract HIV C843A 121 126 Nef;Nef 9;90 12;93 32819562 HIV-1 Nef promotes ubiquitination and proteasomal degradation of p53 tumor suppressor protein by using E6AP. The p53 ubiquitination and degradation was found to be enhanced by Nef with E6AP but not by Nef with E6AP-C843A, a dominant negative E6AP mutant. 2020 Biochemical and biophysical research communications Abstract HIV C843A 106 111 Nef;Nef 67;92 70;95 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Here, we describe Y44A-inactivating mutation of HIV-2 Tat, studying its effect on capsid production, reverse transcription, and the efficiency of proviral transcription. 2020 International journal of molecular sciences Abstract HIV Y44A 18 22 Capsid;Tat;RT 82;54;101 88;57;122 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Our results indicate that the Y44A mutant HIV-2 Tat inhibited the activity and expression of RT (reverse transcriptase), in addition to diminishing Tat-dependent LTR (long terminal repeat) transactivation. 2020 International journal of molecular sciences Abstract HIV Y44A 30 34 RT;RT;Tat;LTR;Tat;LTR 97;93;48;167;148;162 118;95;51;187;151;165 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. The third GRT showed high-level resistance to NRTI, NNRTI, all PI and all INSTI, with additional mutations (H221HY for NNRTI and S147G for INSTI), and a CCR5-tropic virus with a slightly reduced FPR (57.0%). 2020 Antimicrobial resistance and infection control Abstract HIV H221H;H221Y;S147G 108;108;129 115;115;134 INSTI;INSTI;NNRTI;NNRTI;NRTI;PI 74;139;52;119;46;63 79;144;57;124;50;65 32853364 Accumulation of integrase strand transfer inhibitor resistance mutations confers high-level resistance to dolutegravir in non-B subtype HIV-1 strains from patients failing raltegravir in Uganda. HIV integrase-recombinant virus carrying one primary INSTI DRM (N155H or Y143R/S) was susceptible to dolutegravir but highly resistant to raltegravir and elvitegravir (>50-fold change). 2020 The Journal of antimicrobial chemotherapy Abstract HIV N155H;Y143R;Y143S 64;73;73 70;80;80 INSTI;IN 53;4 58;13 32853364 Accumulation of integrase strand transfer inhibitor resistance mutations confers high-level resistance to dolutegravir in non-B subtype HIV-1 strains from patients failing raltegravir in Uganda. Two patients, one with E138A/G140A/Q148R/G163R and one with E138K/G140A/S147G/Q148K, displayed the highest reported resistance to raltegravir, elvitegravir and even dolutegravir. 2020 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138K;G140A;G140A;G163R;Q148K;Q148R;S147G 23;60;29;66;41;78;35;72 28;65;34;71;46;83;40;77 32863004 Conformational landscape of non-B variants of HIV-1 protease: A pulsed EPR study. Findings show that Subtypes F and H HIV-1 PR adopt a primarily closed conformation in the unbound state with two secondary mutations, D60E and I62V, postulated to be responsible for the increased probability for closed conformation. 2020 Biochemical and biophysical research communications Abstract HIV D60E;I62V 134;143 138;147 PR 42 44 32873061 Prevalence of Antiretroviral Drug Resistance Mutations Among Pretreatment and Antiretroviral Therapy-Failure HIV Patients in Uzbekistan. ART-naive cohort I (PDR) included six samples that contained at least one surveillance drug resistance mutation (SDRM) (2.96%), with the most common being K103N mutation (4/6). 2021 AIDS research and human retroviruses Abstract HIV K103N 155 160 32873061 Prevalence of Antiretroviral Drug Resistance Mutations Among Pretreatment and Antiretroviral Therapy-Failure HIV Patients in Uzbekistan. In ART-experienced patients, cohort II, 77.4% (82/106) of viruses contained at least one mutation against PIs, NRTIs, or NNRTIs, with the most common mutations of M184V/I (49.1%; 52/106), K65R (18.9%; 20/106), K103N (23.6%; 25/106), and G190S (22.6%; 24/106). 2021 AIDS research and human retroviruses Abstract HIV G190S;K103N;K65R;M184I;M184V 237;210;188;163;163 242;215;192;170;170 NNRTI;NRTI;PI 121;111;106 127;116;109 32873064 Genetic Characteristics of HIV-1 CRF12_BF First Identified in Guangdong Province, China. In addition, this CRF12_BF strain was confirmed to contain the non-nucleoside reverse transcriptase inhibitor mutation E138A associated with potential low-level resistance against efavirenz and low-level resistance against rilpivirine by the Stanford University HIV Drug Resistance Database program. 2021 AIDS research and human retroviruses Abstract HIV E138A 119 124 NNRTI 63 99 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. Drug resistance-related major mutation was not detected in protease fragments of pol gene, but two major mutations, K103N (6.67%) and Y181C (6.67%), were detected in reverse transcriptase fragments of pol gene. 2020 Infectious disease reports Abstract HIV K103N;Y181C 116;134 121;139 Pol;Pol;PR;RT 81;201;59;166 84;204;67;187 32878449 Genetic Diversity, Complicated Recombination, and Deteriorating Drug Resistance Among HIV-1-Infected Individuals in Wuhan, China. Among the 93 subjects of antiretroviral therapy (ART)-naive, transmitted drug resistance against non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 23.9%, of which V179D/E was the most frequent mutation, accounting for 18.2%. 2021 AIDS research and human retroviruses Abstract HIV V179D;V179E 174;174 181;181 NNRTI;NNRTI 97;146 133;152 32883642 New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains. Among these, IAS 12 exhibited a remarkable antiviral activity against single and double mutants (K103N EC50 = <0.7 nM; Y181C EC50 = <0.7 nM; Y188L EC50 = 21.3 nM; K103N-Y181C EC50 = 6.2 nM), resulting equally or more active than previuosly reported IAS 6 and some approved anti-HIV-1 drugs. 2020 European journal of medicinal chemistry Abstract HIV K103N;K103N;Y181C;Y181C;Y188L 97;163;119;169;141 103;168;124;174;146 32883642 New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains. Docking and molecular dynamics simulations of compound 12 in complex with WT, Y181C, Y188L, K103N and K103N-Y181C RTs clarified a general binding mode that was consistent with biological results. 2020 European journal of medicinal chemistry Abstract HIV K103N;K103N;Y181C;Y181C;Y188L 92;102;78;108;85 97;107;83;113;90 RT 114 117 32883642 New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains. Kinetic experiments disclosed that derivative 12 preferentially binds WT and K103N-Y181C RTs to binary and ternary complexes, respectively. 2020 European journal of medicinal chemistry Abstract HIV K103N;Y181C 77;83 82;88 RT 89 92 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Gain-of-function experiments using SIVcpzPtt Vif revealed that this barrier could be overcome by a single Vif acidic amino acid substitution (M16E). 2020 PLoS pathogens Abstract HIV M16E 142 146 Vif;Vif 45;106 48;109 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. DOR was rationally designed to address limitations associated with other approved NNRTIs, particularly resistance from common NNRTI resistance-associated mutants containing K103N, Y181C, or G190A reverse transcriptase substitutions. 2020 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G190A;K103N;Y181C 190;173;180 195;178;185 RT;NNRTI;NNRTI 196;82;126 217;88;131 32929472 Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. 2020 The Journal of antimicrobial chemotherapy Abstract HIV E138K;G163R;R263K 49;59;42 54;64;47 INSTI;IN 31;96 36;105 32946725 Drug Resistance Spread in 6 Metropolitan Regions, Germany, 2001-2018(1). Phylogenetic and network analysis elucidated numerous cases of shared drug resistance mutations among genetically linked patients; K103N was the most frequently shared mutation. 2020 Emerging infectious diseases Abstract HIV K103N 131 136 32954411 Prevalence of integrase strand transfer inhibitor resistance mutations in antiretroviral-naive HIV-1-infected individuals in Cameroon. Applying a cut-off of 1%, major DRMs to INSTIs were detected in 13 (5.1%) individuals, but only 1 individual harboured an INSTI DRM (E92G) at a nucleotide frequency >=15%. 2021 The Journal of antimicrobial chemotherapy Abstract HIV E92G 133 137 INSTI;INSTI 40;122 46;127 32964671 Transmitted drug resistance to NRTIs and risk of virological failure in naive patients treated with integrase inhibitors. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). 2021 HIV medicine Abstract HIV M184I;M184V 25;25 32;32 32972239 Molecular Epidemiology of HIV-1 in Jiangsu Province, Southeast China: Genotypes and HIV-1 Transmission Networks Among Newly Diagnosed Men Having Sex with Men in 2017. The transmitted HIV drug resistance rate was 4.0% (31/767), and the most common mutations were E138G (n = 4) and G190A (n = 4). 2021 AIDS research and human retroviruses Abstract HIV E138G;G190A 95;113 100;118 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. In the present study, we use molecular dynamics simulations to understand the impact of the N155H mutation in the HIV-1 integrase structure and dynamics, when alone or in combination with Q148H. 2020 Frontiers in molecular biosciences Abstract HIV N155H;Q148H 92;188 97;193 IN 120 129 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Moreover, mutation N155H and the resistance-related mutation Q148H are mutually exclusive for unknown reasons. 2020 Frontiers in molecular biosciences Abstract HIV N155H;Q148H 19;61 24;66 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. While some resistance-related mutations occur near the inhibitor's binding site, the mutation N155H occurs on the opposite side of the drug-interacting Mg2+ ions, thus, not interacting directly with the drug molecules and currently lacking an explanation for its resistance mechanism. 2020 Frontiers in molecular biosciences Abstract HIV N155H 94 99 32974670 In vitro cross-resistance to doravirine in a panel of HIV-1 clones harbouring multiple NNRTI resistance mutations. As expected, single NNRTI mutations K103N and Y181C did not impair doravirine susceptibility (FC 1.4 and 1.8, respectively), while reduced activity was observed with the single M230L or double K103N/Y181C mutations (FC 7.6 and 4.9, respectively). 2021 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K103N;M230L;Y181C;Y181C 36;193;177;46;199 41;198;182;51;204 NNRTI 20 25 32974670 In vitro cross-resistance to doravirine in a panel of HIV-1 clones harbouring multiple NNRTI resistance mutations. METHODS: In vitro phenotypic susceptibility to doravirine was assessed in 10 clinically derived infectious clones with intermediate- to high-level resistance to rilpivirine, etravirine, efavirenz and nevirapine, and in NL4-3 site-directed mutants harbouring K103N, Y181C, M230L or K103N/Y181C NNRTI mutations. 2021 The Journal of antimicrobial chemotherapy Abstract HIV K103N;K103N;M230L;Y181C;Y181C 258;281;272;287;265 263;286;277;292;270 NNRTI 293 298 32977301 Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility. More encouragingly, 14d2 (RF = 0.4) possessed higher antiresistance profile than ETV (RF = 6.3) and K-5a2 (RF = 3.0) toward the double mutant strain F227L + V106A. 2020 European journal of medicinal chemistry Abstract HIV F227L;V106A 149;157 154;162 32978684 In vivo drug resistance mutation dynamics from the early to chronic stage of infection in antiretroviral-therapy-naive HIV-infected men who have sex with men. Four individuals exhibited additional DRMs (M46I/L; I47A; I54M, L100V) as HIV minority populations (abundance, 2-20%) that emerged during the chronic stage but ephemerally. 2020 Archives of virology Abstract HIV I47A;I54M;L100V;M46I;M46L 52;58;64;44;44 56;62;69;50;50 32978684 In vivo drug resistance mutation dynamics from the early to chronic stage of infection in antiretroviral-therapy-naive HIV-infected men who have sex with men. Three of the 10 subjects exhibited the presence of major (abundance, >= 20%) viral populations carrying DRM at early/acute stage that later, at the chronic stage, dropped drastically (V106M) or remained highly abundant (E138A). 2020 Archives of virology Abstract HIV E138A;V106M 220;184 225;189 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). 2020 PloS one Abstract HIV G190A;K103N;V106M 86;52;68 91;57;73 NNRTI 9 14 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated mutations were M184V (n = 17), K70R (n = 7) and D67N (n = 6). 2020 PloS one Abstract HIV D67N;K70R;M184V 133;116;100 137;120;105 NRTI 10 51 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Three samples (12%) had T69D mutation with at least 1 TAM. 2020 PloS one Abstract HIV T69D 24 28 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. PDR mutation to protease inhibitors was found to be low (only G73S; 2% according to the CPR tool). 2020 Retrovirology Abstract HIV G73S 62 66 PR 16 24 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. The most frequently observed NNRTIs-associated mutations common to both algorithms were K103N (2%), Y188L (2%), K101E (2%), and V106A (2%), while E138A (2%) was observed according to IAS-USA only. 2020 Retrovirology Abstract HIV E138A;K101E;K103N;V106A;Y188L 146;112;88;128;100 151;117;93;133;105 NNRTI 29 35 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. Y115F and M184V (mutations that confer resistance to NRTIs) dual mutations were detected according to both criteria in a single study participant (2%). 2020 Retrovirology Abstract HIV M184V;Y115F 10;0 15;5 NRTI 53 58 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Further studies are needed to determine optimal antiretroviral therapy for patients with the M184V/I mutation. 2020 SAGE open medicine Abstract HIV M184I;M184V 93;93 100;100 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Methods: A retrospective chart review was conducted of 100 treatment-experienced patients harboring the M184V/I mutation seen at an urban HIV clinic. 2020 SAGE open medicine Abstract HIV M184I;M184V 104;104 111;111 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Objectives: The optimal antiretroviral therapy for patients with the M184V/I mutation is not known. 2020 SAGE open medicine Abstract HIV M184I;M184V 69;69 76;76 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Regimens containing less than 3 active agents may maintain virologic suppression in patients with the M184V/I mutation. 2020 SAGE open medicine Abstract HIV M184I;M184V 102;102 109;109 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The primary objective of this study was to determine the efficacy of various antiretroviral therapies in patients with HIV and the M184V/I mutation based on the number of active antiretroviral agents. 2020 SAGE open medicine Abstract HIV M184I;M184V 131;131 138;138 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. CONCLUSION: The accumulation of Pol S653A/T/L escape mutants critically affected the control of HIV-1 by SL9-specific T cells and led to a poor clinical outcome in the subtype A/E-infected individuals having the detrimental HLA-C*15:05 allele. 2021 AIDS (London, England) Abstract HIV S653A;S653L;S653T 36;36;36 45;45;45 Pol 32 35 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. T-cell responders infected with these mutants showed significantly lower CD4 T-cell counts than those with the wild-type virus or Pol S653K/Q mutants, which are not associated with HLA-C*15:05. 2021 AIDS (London, England) Abstract HIV S653K;S653Q 134;134 141;141 Pol 130 133 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. HIV-1 DRM discordance was found in 3/26 (11.5%); 1 had I84IT and another had M46MI in CSF only. 2020 Medicine Abstract HIV I84I;I84T;M46I;M46M 55;55;77;77 60;60;82;82 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. The third had K101E in plasma and V106 M in CSF.Our findings suggest that HIV-1 escape and DRM discordance may occur at lower rates in participants with advanced HIV-disease and CM compared to those with HIV associated neurocognitive impairment. 2020 Medicine Abstract HIV K101E;V106M 14;34 19;40 33041100 DNA adjuvant Amiloride conjunct long immunization interval promote higher antibody responses to HIV-1 gp41 and gp140 immunogens. In the present study, we immunized Balb/c mice using trimeric gp41-expressing plasmid for prime and monomeric gp41 or trimeric gp140 protein as well as a mutant (Q577A) for boost. 2020 Vaccine Abstract HIV Q577A 162 167 gp140;gp41;gp41 127;62;110 132;66;114 33041100 DNA adjuvant Amiloride conjunct long immunization interval promote higher antibody responses to HIV-1 gp41 and gp140 immunogens. Q577A mutant was benefit for trimeric gp140 boost in the production of binding Abs but harmful to inducing neutralizing Abs, while this mutant in monomeric gp41 presented the opposite trend which may be associated with the immunogen structures. 2020 Vaccine Abstract HIV Q577A 0 5 gp140;gp41 38;156 43;160 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Moreover, we found that the ability of TRIM5alpha to stimulate IFN-beta expression in response to recognition of a TRIM5alpha-restricted HIV-1 capsid mutant (P90A) was abrogated in cells lacking autophagy factors. 2020 PLoS pathogens Abstract HIV P90A 158 162 Capsid 143 149 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Stimulation of human macrophage-like cells with the P90A virus protected them against subsequent infection with an otherwise resistant wild type HIV-1 in a manner requiring TRIM5alpha, BECN1, and ULK1. 2020 PLoS pathogens Abstract HIV P90A 52 56 33076683 Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019. Conclusions: In patients with HIV and the M184V mutation, the PI + INI ART has shown a greater decrease in control VL and, thus, a good virological response. 2021 AIDS research and human retroviruses Abstract HIV M184V 42 47 IN;PI 67;62 70;64 33076683 Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019. Introduction: In patients with HIV in antiretroviral treatment (ART) and virological failure to the first-line regimen, establishing a therapeutic regimen after having identified the M184V mutation, which confers ART resistance, represents a dilemma. 2021 AIDS research and human retroviruses Abstract HIV M184V 183 188 33076683 Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019. Methods: A retrospective cohort study was developed based on the information of the HIV program participants with the M184V mutation. 2021 AIDS research and human retroviruses Abstract HIV M184V 118 123 33076683 Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019. Objective: To compare the virological response of the therapeutic regimens prescribed to patients with HIV who presented the M184V mutation in two national hospitals in Lima, Peru, during the years 2008 to 2019, and to determine the risk factors associated with poor virological response. 2021 AIDS research and human retroviruses Abstract HIV M184V 125 130 33101270 The Signature Amino Acid Residue Serine 31 of HIV-1C Tat Potentiates an Activated Phenotype in Endothelial Cells. The natural cysteine to serine variation at position 31 of Tat in HIV-1C disrupts the dicysteine motif attenuating the chemokine function of Tat. 2020 Frontiers in immunology Abstract HIV C31S 12 55 Tat;Tat 59;141 62;144 33105474 Clinical and Public Health Implications of HIV- Genetic Diversity and Drug Resistance Mutations in Angola: A Systematic Review. One DRM in the PIs was found (I54 M), 22 in the nucleoside reverse transcriptase inhibitors (NRTIs), and 18 in the non-nucleoside reverse transcriptase inhibitors (NNRTIs). 2020 AIDS reviews Abstract HIV I54M 30 35 NNRTI;NNRTI;NRTI;NRTI;PI 164;115;93;48;15 170;151;98;80;18 33105474 Clinical and Public Health Implications of HIV- Genetic Diversity and Drug Resistance Mutations in Angola: A Systematic Review. Over the past 40 years, the frequency of the DRM M184V (50-64.3%, p=0.363), G190A (17.2-46.2%, p=0.021), and K103N (34.5-42.3%, p=0.551) increased, while the frequency of Y181C (17.2-7.7%, p=0.289) decreased. 2020 AIDS reviews Abstract HIV G190A;K103N;M184V;Y181C 76;109;49;171 81;114;54;176 33105474 Clinical and Public Health Implications of HIV- Genetic Diversity and Drug Resistance Mutations in Angola: A Systematic Review. The major DRM in the NRTIs was the M184V, whereas the G190A, K103N, and Y181C were the major DRMs in the NNRTIs. 2020 AIDS reviews Abstract HIV G190A;K103N;M184V;Y181C 54;61;35;72 59;66;40;77 NNRTI;NRTI 105;21 111;26 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Among all Vpu variants, three of the variants having serine substitution (serine-52 and serine-56 conversion to isoleucine; S52I and S56I) had lost their functional beta-TrcP binding motif. 2020 BioResearch open access Abstract HIV S52I;S56I 124;133 128;137 Vpu 10 13 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Three-dimensional prediction models revealed that Asp69Val, Ser251Phe, and Ile115Phe caused neutral effects while Thr47Ser and Tyr79produced a deleterious effect reducing VP1 stability. 2020 International journal of molecular sciences Abstract HIV D69V;I115F;S251F;T47S;Y79P 50;75;60;114;127 58;84;69;122;135 Asp 50 53 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. VP1 from two urine specimens had either Thr47Ser or Ile115Phe substitution, whereas VP1 of one plasma contained Asp69Val and Ser251Phe substitutions plus deletion ( ) of Tyr79. 2020 International journal of molecular sciences Abstract HIV D69V;I115F;S251F;T47S 112;52;125;40 120;61;134;48 Asp 112 115 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. According to the epidemiological history and phylogenetic data, in late pregnancy of the mother, the infant's father transmitted HIV-1 to her, and then the mother to the baby, leading to the transmission of V106I as a common mutation of three persons. 2020 Infection and drug resistance Abstract HIV V106I 207 212 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Mother also acquired K101E (41.03%), K103N (27.56%) and minor mutation of V106M (4.30%) after improperly discontinuing antiretroviral regimen of lamivudine (3TC), tenofovir (TDF) and efavirenz (EFV). 2020 Infection and drug resistance Abstract HIV K101E;K103N;V106M 21;37;74 26;42;79 33136738 High Prevalence of HIV-1 Drug Resistance and Dynamics of Transmission Among High-Risk Populations in Port-au-Prince, Haiti. Five clusters (62.5%) had shared DRMs, and K103N and M184V were the main shared mutations. 2020 Journal of acquired immune deficiency syndromes (1999) Abstract HIV K103N;M184V 43;53 48;58 33143751 Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had >= 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. 2020 AIDS research and therapy Abstract HIV M184I;M184V;K65R 155;155;209 162;162;213 NNRTI 110 115 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. A combination of four mutations (S126del, H127del, T122A, and G123E) in the p17 matrix of baseline virus generated a similar 4-fold decrease in susceptibility to LPV but not darunavir. 2020 mBio Abstract HIV G123E;H127del;S126del;T122A 62;42;33;51 67;49;40;56 Matrix 80 86 33166562 HIV-1 gp41 genetic diversity and enfuvirtide resistance-associated mutations among enfuvirtide-naive patients in southern China. One major DRM (L44 M), many secondary DRMs (including N126 K, E137 K, S138A), and lots of polymorphisms were found in the study, which have been proved to elevate resistance to ENF. 2021 Virus research Abstract HIV E137K;L44M;N126K;S138A 62;15;54;70 68;20;60;75 33170745 Determination of reverse transcriptase inhibitor resistance mutations in HIV-1 infected children in Cote d'Ivoire. Frequently encountered resistance mutations were for NRTIs: M184V (88%), TAMs (67%), T215F/I/V/Y (33%), and L74I/V (24%); for NNRTIs: K103N/S (74%), P225H (26%), and G190A/E/Q (24%). 2021 Genome Abstract HIV G190A;G190E;G190Q;K103N;K103S;L74I;L74V;M184V;P225H;T215F;T215I;T215V;T215Y 166;166;166;134;134;108;108;60;149;85;85;85;85 175;175;175;141;141;114;114;65;154;96;96;96;96 NNRTI;NRTI 126;53 132;58 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. A series of biochemical experiments showed that the double mutations Y120F/Q125H, but not either single mutation, impaired Nef's ability to antagonize SERINC5 and was associated with decreasing virion infectivity and viral replication in primary lymphocytes. 2020 Scientific reports Abstract HIV Q125H;Y120F 75;69 80;74 Nef 123 126 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. By breaking down the specific HLA allele-associated mutations, we found that a number of the HLA-B*51:01-associated Y120F and Q125H mutations were most significantly associated with a reduced plasma viral load. 2020 Scientific reports Abstract HIV Q125H;Y120F 126;116 131;121 33175558 Multiple Molecular Dynamics Simulations of the Inhibitor GRL-02031 Complex with Wild Type and Mutant HIV-1 Protease Reveal the Binding and Drug-Resistance Mechanism. On the basis of detail analysis of the simulations, we revealed key characteristics that constitute the drug resistance of four mutation HIV-1 proteases toward GRL-02031: substitution of the side chain in these four mutation residues leads to a change in the distances between the flaps and catalytic sites, thereby reducing the affinity for GRL-02031 with these four mutation proteases, even though the L76V and N88D residues cannot directly contact GRL-02031. 2020 Langmuir Abstract HIV L76V;N88D 404;413 408;417 PR;PR 143;377 152;386 33175558 Multiple Molecular Dynamics Simulations of the Inhibitor GRL-02031 Complex with Wild Type and Mutant HIV-1 Protease Reveal the Binding and Drug-Resistance Mechanism. To elucidate the binding mechanism of HIV-1 protease with promising inhibitor GRL-02031 and further to probe the resistance mechanism associated with mutations (I47V, L76V, V82A, and N88D) to the inhibitor, we applied multiple molecular dynamics (MMD) simulations along with energy analysis by the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and solvated interaction energy (SIE) methodology on specific HIV-1 protease with GRL-0231 complexes. 2020 Langmuir Abstract HIV I47V;L76V;N88D;V82A 161;167;183;173 165;171;187;177 PR;PR 44;427 52;435 33184634 Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. 2021 The Journal of antimicrobial chemotherapy Abstract HIV S153F;S153Y 17;7 22;12 33184634 Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. 2021 The Journal of antimicrobial chemotherapy Abstract HIV R263K;S153F;S153Y 30;10;19 35;15;24 IN 146 155 33184634 Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir. RESULTS: R263K emerged first, followed by the addition of S153F at Week 12. 2021 The Journal of antimicrobial chemotherapy Abstract HIV R263K;S153F 9;58 14;63 33184634 Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir. We confirmed the coexistence of S153F and R263K on single viral genomes. 2021 The Journal of antimicrobial chemotherapy Abstract HIV R263K;S153F 42;32 47;37 33184634 Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. 2021 The Journal of antimicrobial chemotherapy Abstract HIV R263K;S153F 141;131 146;136 IN 147 156 33196554 Simulating HIV Breakthrough and Resistance Development During Variable Adherence to Antiretroviral Treatment. MT-2 cells were infected with wild-type or low frequency M184V HIV-1, exposed to drug combinations, monitored for VB, and rebound virus was deep sequenced. 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V 57 62 33196554 Simulating HIV Breakthrough and Resistance Development During Variable Adherence to Antiretroviral Treatment. RESULTS: Cultures infected with wild-type or low frequency M184V HIV-1 showed no VB with BIC+FTC+TAF at drug concentrations corresponding to Cmin, Cmin - 1, or Cmin - 2 but breakthrough did occur in 26 of 36 cultures at Cmin - 3, where the M184V variant emerged in one culture. 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;M184V 59;240 64;245 33200210 Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study. Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively. 2021 The Journal of antimicrobial chemotherapy Abstract HIV K65E;K65N;K65R;M184I;M184V 67;67;67;52;52 75;75;75;60;60 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. In addition, this case highlights the need for viral load monitoring in patients on dolutegravir-containing regimens in settings with a high prevalence of the M184V/I mutation such as in low-income countries. 2020 Viruses Abstract HIV M184I;M184V 159;159 166;166 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. This case illustrates that dolutegravir-containing triple-therapy should be prescribed with caution to patients with pre-existing M184V/I mutation and poor efficacy of the reverse transcriptase inhibitor backbone. 2020 Viruses Abstract HIV M184I;M184V 130;130 137;137 RT 172 193 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. We describe a rare case of a patient with pre-existing M184V/I mutation and virological failure on a dolutegravir/lamivudine/abacavir regimen with the emergence of integrase strand transfer inhibitor resistance mutations. 2020 Viruses Abstract HIV M184I;M184V 55;55 62;62 IN 164 173 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Mutations associated with antiretroviral drugs include (V82A+I84IV), (L10F+Q58E), (L10F+V82Y), L10FV, L33LF, L89LMV, M184V, E138A, V106I, and V179VD. 2020 Medicine Abstract HIV E138A;I84I;I84V;L10F;L10F;L10F;L10V;L33F;L33L;L89L;L89M;L89V;M184V;Q58E;V106I;V179D;V179V;V82A;V82Y 124;61;61;70;95;83;95;102;102;109;109;109;117;75;131;142;142;56;88 129;66;66;74;100;87;100;107;107;115;115;115;122;79;136;148;148;60;92 33287618 First Assessment of Acquired HIV-1 Drug Resistance and Mutation Patterns in Suriname. The most common DRMs were M184V (23.6%) and K103N (18.8%). 2021 AIDS research and human retroviruses Abstract HIV K103N;M184V 44;26 49;31 33287631 Near Full-Length Genomic Characterization of a Novel HIV-1 B/C Recombinant Form Identified in Guangdong Province, China. In addition, this B/C recombinant strain contained the non-nucleoside reverse transcriptase inhibitor resistance mutation K103N and the integrase strand transfer inhibitor other resistance mutation L74I according to the Stanford University HIV Drug Resistance Database program. 2021 AIDS research and human retroviruses Abstract HIV K103N;L74I 122;198 127;202 NNRTI;IN 55;136 91;145 33300183 Week 96 resistance analyses of the once-daily, single-tablet regimen (STR) darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the phase 3 randomized AMBER and EMERALD trials. M184I/V (emtricitabine RAM) was detected in one patient in each arm of AMBER. 2021 Journal of medical virology Abstract HIV M184I;M184V 0;0 7;7 33314454 A synergy of activity, stability, and inhibitor-interaction of HIV-1 protease mutants evolved under drug-pressure. A clinically-relevant, drug-resistant mutant of HIV-1 protease (PR), termed Flap+(I54V) and containing L10I, G48V, I54V and V82A mutations, is known to produce significant changes in the entropy and enthalpy balance of drug-PR interactions, compared to wild-type PR. 2021 Protein science Abstract HIV G48V;I54V;I54V;L10I;V82A 109;82;115;103;124 113;86;119;107;128 PR;PR;PR;PR 64;224;263;54 66;226;265;62 33314454 A synergy of activity, stability, and inhibitor-interaction of HIV-1 protease mutants evolved under drug-pressure. A similar mutant, Flap+(I54A) , which evolves from Flap+(I54V) and contains the single change at residue 54 relative to Flap+(I54V) , does not. 2021 Protein science Abstract HIV I54A;I54V;I54V 24;57;126 28;61;130 33314454 A synergy of activity, stability, and inhibitor-interaction of HIV-1 protease mutants evolved under drug-pressure. To understand the molecular basis of V54A evolution, we compared nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, isothermal titration calorimetry, and enzymatic assay data from four PR proteins: PR (pWT), Flap+(I54V) , Flap+(I54A) , and Flap+(I54) , a control mutant that contains only L10I, G48V and V82A mutations. 2021 Protein science Abstract HIV G48V;I54A;I54V;L10I;V54A;V82A 318;251;237;312;37;327 322;255;241;316;41;331 PR;PR 208;221 210;223 33314454 A synergy of activity, stability, and inhibitor-interaction of HIV-1 protease mutants evolved under drug-pressure. Yet, how Flap+(I54A) behaves in solution is not known. 2021 Protein science Abstract HIV I54A 15 19 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. BACKGROUND: The ability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) to maintain virologic suppression in participants with M184V and/or M184I resistance mutations from historical genotypic reports when switching from a tenofovir disoproxil fumarate-based or abacavir (ABC)-based regimen was investigated. 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 167;154 172;159 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. CONCLUSIONS: The presence of the resistance mutations M184V/I did not jeopardize the efficacy of switching to E/C/F/TAF in virologically suppressed adults. 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 54;54 61;61 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. METHODS: Virologically suppressed adults with HIV and documented M184V/I on historical genotypic records switched to E/C/F/TAF from a tenofovir disoproxil fumarate-based or ABC-based regimen. 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 65;65 72;72 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. RESULTS: M184V alone was reported in 82.8% of 64 participants; 9.4% and 7.8% had M184I and M184V/I, respectively, and 43.8% had archived M184V/I (baseline DNA). 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184I;M184I;M184V;M184V;M184V 81;91;137;91;137;9 86;98;144;98;144;14 33316353 Conditional activation of an HIV-1 protease attenuated mutant by a leucine zipper dimerization motif. However, introducing T26S (a PR activity-attenuated mutation) into DWzPR strongly impaired Gag cleavage, except when the native C-terminal p6* tetrapeptide remained at the LZ/PR junction. 2021 Virus research Abstract HIV T26S 21 25 Gag;Gag;PR;PR 91;139;29;175 94;141;31;177 33316353 Conditional activation of an HIV-1 protease attenuated mutant by a leucine zipper dimerization motif. LZ insertion at the PR C-terminus still strongly enhanced PR T26S Gag cleavage. 2021 Virus research Abstract HIV T26S 61 65 Gag;PR;PR 66;20;58 69;22;60 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. Among them, no major resistance mutations to INSTIs were identified, and four accessory mutations, including T97A (0.12%, 1/827), A128T (0.24%, 2/827), E157Q (0.85%, 7/827), and G163R (0.24%, 2/827), were found in twelve individuals. 2020 Infection and drug resistance Abstract HIV A128T;E157Q;G163R;T97A 130;152;178;109 135;157;183;113 INSTI 45 51 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. Two patient samples contained the G163R mutation conferring low-level resistance to elvitegravir and raltegravir. 2020 Infection and drug resistance Abstract HIV G163R 34 39 33324386 Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. HPV81 showed an amino-acid substitution within the BC loop (N75Q) and the FGb loop (T315N). 2020 Frontiers in microbiology Abstract HIV N75Q;T315N 60;84 64;89 33340914 Design, synthesis, and evaluation of "dual-site"-binding diarylpyrimidines targeting both NNIBP and the NNRTI adjacent site of the HIV-1 reverse transcriptase. Of note, 14c exhibited potent activity against the single mutant strain E138K (EC50 = 10.6 nM), being comparable with ETR (EC50 = 9.80 nM) and 3.5-fold more potent than that of compound 7 (EC50 = 37.3 nM). 2021 European journal of medicinal chemistry Abstract HIV E138K 72 77 33347449 The genotype distribution, infection stage and drug resistance mutation profile of human immunodeficiency virus-1 among the infected blood donors from five Chinese blood centers, 2014-2017. 48 DRMs were identified from 43 samples, indicating a drug resistance prevalence of 12.1% (43/356), which include seven protease inhibitors (PIs) accessory DRMs (Q58E, L23I and I84M), two PIs major DRMs (M46I, M46L), seven nucleoside RT inhibitors DRMs (D67N, K70Q, K219R and M184L), and 32 non-nucleoside RT inhibitors DRMs (K103N, V179E, K238N, V179D, E138G, G190E, A98G, Y188D and E138A). 2020 PloS one Abstract HIV A98G;D67N;E138A;E138G;G190E;I84M;K103N;K219R;K238N;K70Q;L23I;M184L;M46I;M46L;Q58E;V179D;V179E;Y188D 368;254;384;354;361;177;326;266;340;260;168;276;204;210;162;347;333;374 372;258;389;359;366;181;331;271;345;264;172;281;208;214;166;352;338;379 PR;PI;PI;RT;RT 120;141;188;234;306 128;144;191;236;308 33352387 Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C. Compounds I-7 and I-9 demonstrated higher selectivity towards the Y181C mutant than against the wild-type RT, in nucleotide incorporation inhibition assays. 2021 Bioorganic & medicinal chemistry Abstract HIV Y181C 66 71 RT 106 108 33352387 Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C. Y181C is selected in patients receiving nevirapine, etravirine and rilpivirine, and together with K103N is the most prevalent NNRTI-associated mutation in HIV-infected patients. 2021 Bioorganic & medicinal chemistry Abstract HIV K103N;Y181C 98;0 103;5 NNRTI 126 131 HIV infections 155 167 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. Of the 38 patients diagnosed in 2017 who had both NGS and population sequencing data, none had INSTI resistance-associated mutations by population sequencing; however, NGS detected four more INSTI resistance-associated mutations with low frequencies (G163R 3.25%, S153F 3.21%, S153Y 1.36% and Y143H 2.06%). 2020 Infection and drug resistance Abstract HIV G163R;S153F;S153Y;Y143H 251;264;277;293 257;269;282;298 INSTI;INSTI 95;191 100;196 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. The most common INSTI resistance-associated mutations were G163K (0.4%) and E138A (0.4%). 2020 Infection and drug resistance Abstract HIV E138A;G163K 76;59 81;64 INSTI 16 21 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. Two patients with S153F and S153Y low frequencies mutations started INSTI-based highly active antiretroviral therapy, and none had virological failure by week 48. 2020 Infection and drug resistance Abstract HIV S153F;S153Y 18;28 23;33 INSTI 68 73 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. INSTI DRMs were detected almost exclusively below the 20% detection threshold, most commonly Y143H (0.4%), Q148R (0.4%) and T66I (0.4%). 2021 HIV medicine Abstract HIV Q148R;T66I;Y143H 107;124;93 112;128;98 INSTI 0 5 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. TDR was based on the WHO 2009 surveillance definition with the addition of reverse transcriptase (RT) mutations T215N and E138K, and integrase strand transfer inhibitor (INSTI) surveillance mutations (Stanford HIVdb). 2021 HIV medicine Abstract HIV E138K;T215N 122;112 127;117 INSTI;IN;RT;RT 170;133;75;98 175;142;96;100 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Using the 2% detection threshold, individual DRMs with the highest prevalence were: PI M46IL (5.5%), RT K103NS (3.5%), RT G190ASE (3.1%), T215ISCDVEN (2.5%), RT M41L (2.2%), RT K219QENR (1.7%) and PI D30N (1.6%). 2021 HIV medicine Abstract HIV G190A;G190E;G190S;K103N;K103S;K219E;K219N;K219Q;K219R;D30N;M41L;M46I;M46L;T215C;T215D;T215E;T215I;T215N;T215S;T215V 122;122;122;104;104;177;177;177;177;200;161;87;87;138;138;138;138;138;138;138 129;129;129;110;110;185;185;185;185;204;165;92;92;149;149;149;149;149;149;149 PI;PI;RT;RT;RT;RT 84;197;101;119;158;174 86;199;103;121;160;176 33390085 Detection of Drug Resistance Mutations in the Reverse Transcriptase Gene of HIV-1-Infected North Indian Population Failing First-Line Antiretroviral Therapy "A Follow-Up Cohort Study". Drug resistance mutation M184V (ATG to GTA) (63.15%) associated with lamivudine and abacavir and K103N (AAG or AAA to AAU) (36.84%) associated with efavirenz and nevirapine were predominantly identified in first-line ART failure patients. 2021 AIDS research and human retroviruses Abstract HIV K103N;M184V 97;25 102;30 33390426 A Single Amino Acid Substitution at the HIV-1 Protease Termini Dimer Interface Significantly Reduces Viral Particles Processing Efficiency. We made an alanine substitution for valine 3 (V3) or leucine 97 (L97) at the termini dimer interface and tested their proteolytic activity. 2021 Japanese journal of infectious diseases Abstract HIV V3A 11 44 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. We found that some mutations, such as G123E and H219Q, involve direct interaction with cleavage site residues to influence their local environment, while certain mutations in the matrix domain lead to the enrichment of lipids important for Gag targeting and assembly. 2021 Computational and structural biotechnology journal Abstract HIV G123E;H219Q 38;48 43;53 Matrix;Gag 179;240 185;243 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Q135P in the vif gene is significantly associated with rapid progression to AIDS (p < 0.01). 2021 Journal of ginseng research Abstract HIV Q135P 0 5 Vif 13 16 AIDS 76 80 33462791 HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil. 20% in HIV-1B (p = 0.004), and that of substitution Q63E in HIV-1C was 80% and 20% in HIV-1B (p < 0.0001). 2021 Journal of neurovirology Abstract HIV Q63E 52 56 33462791 HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil. The frequency of C31S and other key point mutations in HIV-1 Tat C in Brazil were similar to those described in Africa, although lower than those in India. 2021 Journal of neurovirology Abstract HIV C31S 17 21 Tat 61 64 33462791 HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil. The frequency of C31S substitution on HIV-1 Tat C in Brazil was 82% vs. 2021 Journal of neurovirology Abstract HIV C31S 17 21 Tat 44 47 33462791 HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil. The frequency of the R57S substitution among the HIV-1C sequences from Brazil was 74% vs. 2021 Journal of neurovirology Abstract HIV R57S 21 25 33462791 HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil. The mutation P60Q was more frequent in HIV-1B than in HIV-1C (55% and 6.12%, respectively, p < 0.0001)). 2021 Journal of neurovirology Abstract HIV P60Q 13 17 33466381 Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation. The MD simulations of Asn425Gly mutant provide a less dynamic gp120 in the presence of NBD-557 without incapacitating the binding enthalpy of NBD-557. 2021 Molecules (Basel, Switzerland) Abstract HIV N425G 22 31 gp120 62 67 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Nonnucleoside RT inhibitors (NNRTIs) can interfere with the initiation of plus-strand DNA synthesis by enhancing PPT removal, while HIV RT connection subdomain mutations N348I and N348I/T369I mitigate this effect by altering RNase H cleavage specificity. 2021 Viruses Abstract HIV N348I;N348I;T369I 180;170;186 185;175;191 NNRTI;RT;RT 29;14;136 35;16;138 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The combination N348I/T369I in HIV-1BH10 RT has a dominant effect on the RNase H cleavage specificity at the PPT/U3 site. 2021 Viruses Abstract HIV N348I;T369I 16;22 21;27 RT 41 43 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. 2021 BMC infectious diseases Abstract HIV K103N;Y181C;Y181I 38;26;26 43;33;33 33480094 Virological response and resistance profile in highly treatment-experienced HIV-1-infected patients switching to dolutegravir plus boosted darunavir in clinical practice. Among 13 non-responding patients for whom a genotypic resistance test result at failure was available, only two (15.4%) accumulated further resistance in integrase (Y143C/H/R; S147G and N155H) and protease (V32I, L33F, I54L). 2021 HIV medicine Abstract HIV I54L;L33F;N155H;S147G;V32I;Y143C;Y143H;Y143R 219;213;186;176;207;165;165;165 223;217;191;181;211;174;174;174 IN;PR 154;197 163;205 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Conversely, Env incorporation can be rescued by a compensatory mutation in the MA trimer interface (Q63R). 2021 The Journal of biological chemistry Abstract HIV Q63R 100 104 Env;Matrix 12;79 15;81 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. In this study, we employed NMR spectroscopy, X-ray crystallography, and sedimentation techniques to characterize the structure and trimerization properties of HIV-1 MA A45E, Q63R, T70R, and L75G mutant proteins. 2021 The Journal of biological chemistry Abstract HIV A45E;L75G;Q63R;T70R 168;190;174;180 172;194;178;184 Matrix 165 167 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Nonconservative mutations in the trimer interface of MA (A45E, T70R, and L75G) were found to impair Env incorporation and infectivity, leading to the hypothesis that MA trimerization is an obligatory step for Env incorporation. 2021 The Journal of biological chemistry Abstract HIV A45E;L75G;T70R 57;73;63 61;77;67 Env;Env;Matrix;Matrix 100;209;53;166 103;212;55;168 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The high-resolution X-ray structure of the unmyristoylated MA Q63R protein revealed hydrogen bonding between the side chains of adjacent Arg-63 and Ser-67 on neighboring MA molecules, providing the first structural evidence for an additional intermolecular interaction in the trimer interface. 2021 The Journal of biological chemistry Abstract HIV Q63R 62 66 Matrix;Matrix 59;170 61;172 33508465 Design and exploration of C-3 benzoic acid bioisosteres and alkyl replacements in the context of GSK3532795 (BMS-955176) that exhibit broad spectrum HIV-1 maturation inhibition. A cyclohexene carboxylic acid provided exceptional inhibition of wild-type, V370A and DeltaV370 mutant viruses in addition to a suitable PK profile following oral dosing to rats. 2021 Bioorganic & medicinal chemistry letters Abstract HIV DeltaV370;V370A 86;76 95;81 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Cryo-tomography reveals that K25A virions have a severe assembly defect that inhibits the formation of mature capsid cones. 2021 PLoS pathogens Abstract HIV K25A 29 33 Capsid 110 116 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Monitoring both the kinetics and morphology of capsids assembled in vitro reveals that while mutation K25A can still form tubes, the ability of IP6 to drive assembly of capsid cones has been lost. 2021 PLoS pathogens Abstract HIV K25A 102 106 Capsid;Capsid 47;169 54;175 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Compared to wild-type hDAT, the maximal velocity (Vmax) of [3H]dopamine uptake was decreased in D381L and Y88F/D206L/H547A, increased in D206L/H547A, and unaltered in D206L. 2021 Journal of neuroimmune pharmacology Abstract HIV D206L;H547A;Y88F;D206L;D206L;D381L;H547A 111;117;106;167;137;96;143 116;122;110;172;142;101;148 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Furthermore, H547A displayed an increase in palmitoylation inhibitor-induced inhibition of dopamine uptake relative to wide-type hDAT, indicating a change in basal palmitoylation in H547A. 2021 Journal of neuroimmune pharmacology Abstract HIV H547A;H547A 13;182 18;187 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. H547A-induced outward-open transport conformational state was further validated by enhanced accessibility to MTSET ([2-(trimethylammonium)ethyl]-methanethiosulfonate) of an inserted cysteine (I159C) on a hDAT background. 2021 Journal of neuroimmune pharmacology Abstract HIV I159C;H547A 192;0 197;5 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Mutational effects of hDAT on the transporter conformation were evidenced by attenuation of zinc-induced increased [3H]WIN35,428 binding in D206L/H547A and Y88F/D206A/H547A and enhanced basal MPP+ efflux in D206L/H547A. 2021 Journal of neuroimmune pharmacology Abstract HIV D206A;H547A;Y88F;D206L;D206L;H547A;H547A 161;167;156;140;207;146;213 166;172;160;145;212;151;218 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Recombinant TatR1 - 86 inhibited dopamine uptake in wild-type hDAT, which was attenuated in either DAT mutants (D206L, D206L/H547A, and Y88F/D206L/H547A) or mutated TatR1 - 86 (K19A and C22G), demonstrating perturbed Tat-DAT interaction. 2021 Journal of neuroimmune pharmacology Abstract HIV D206L;H547A;Y88F;C22G;D206L;D206L;H547A;K19A 141;147;136;186;112;119;125;177 146;152;140;190;117;124;130;182 Tat;Tat;Tat 12;165;217 15;168;220 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. These results demonstrate that Y88F, D206L, and H547A attenuate Tat inhibition while preserving DA uptake, providing insights into identifying targets for improving DAT-mediated dopaminergic dysregulation. 2021 Journal of neuroimmune pharmacology Abstract HIV D206L;H547A;Y88F 37;48;31 42;53;35 Tat 64 67 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. Most cases of TDR were related to resistance to non-nucleoside reverse transcriptase inhibitors (4.87%) and V179E was the most common mutation detected. 2021 BMC infectious diseases Abstract HIV V179E 108 113 NNRTI 48 84 33567378 Identification of novel potent HIV-1 inhibitors by exploiting the tolerant regions of the NNRTIs binding pocket. Compounds 16a1 and 16b1 turned out to be the most potent inhibitors against WT and mutant HIV-1 strains (L100I, K103N, and E138K), with EC50 values ranging from 0.007 muM to 0.043 muM. 2021 European journal of medicinal chemistry Abstract HIV E138K;K103N;L100I 123;112;105 128;117;110 33579120 Drug resistance mutations among virological failure HIV-1 infected patients in Malaysia. The most common mutation for NRTIs was M184V while K103N mutation was detected in the majority of patients who were treated with NNRTIs. 2016 Tropical biomedicine Abstract HIV K103N;M184V 51;39 56;44 NNRTI;NRTI 129;29 135;34 33579120 Drug resistance mutations among virological failure HIV-1 infected patients in Malaysia. The most commonly observed mutations for major PI and minor PI seen among the study population were V82A/T and L10V, respectively. 2016 Tropical biomedicine Abstract HIV L10V;V82A;V82T 111;100;100 115;106;106 PI;PI 47;60 49;62 33592343 Transmitted drug resistance among HIV-1 drug-naive patients in Greece. The most frequent resistance sites were E138A (9.6%), K103N (6.4%), and K101E (2.1%). 2021 International journal of infectious diseases Abstract HIV E138A;K101E;K103N 40;72;54 45;77;59 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). At failure, M184V and major PI mutations were detected in 1/17 and 5/15 patients in the bPI arm and in 2/2 and 0/3 in the bPI+lamivudine arm, respectively. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184V 12 17 PI 28 30 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). BACKGROUND: The ANRS12286/MOBIDIP trial showed that boosted protease inhibitor (bPI) plus lamivudine dual therapy was superior to bPI monotherapy as maintenance treatment in subjects with a history of M184V mutation. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184V 201 206 PR 60 68 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). CONCLUSIONS: Using UDS evidenced that archiving of M184V in HIV-DNA is heterogeneous despite past historical M184V in 96% of cases. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184V;M184V 51;109 56;114 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). Longer duration of first-line treatment, higher plasma viral load at first-line treatment failure and higher baseline HIV-DNA load were associated with the archived M184V. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184V 165 170 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). M184I mutation was always associated with a STOP codon, suggesting defective virus. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184I 0 5 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). OBJECTIVES: We aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF). 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 54;54 61;61 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). RESULTS: M184V and I mutations were detected in HIV-DNA for 173/252 (69%) and 31/252 (12%) of participants, respectively. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184V 9 14 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). The 48 week estimated probability of remaining free from VF was comparable with or without the M184V/I mutation for dual therapy. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 95;95 102;102 33624081 Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial). The proportion of M184V/I variants was described and the association between the M184V/I mutation at 1% of threshold and VF was explored with logistic regression models. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184I;M184V;M184V 18;81;18;81 25;88;25;88 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in < 20% of the population. 2021 BMC infectious diseases Abstract HIV K103N;K65R;M184V;V82A 41;26;32;58 46;30;37;62 RT;PI 8;51 11;53 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n = 13) in protease and K65R (n = 5), K103N (n = 7) and M184V (n = 5) in reverse transcriptase. 2021 BMC infectious diseases Abstract HIV K103N;K65R;M184V;V82A 152;138;170;99 157;142;175;103 PR;RT 125;187 133;208 33635845 Pre-treatment integrase inhibitor resistance is uncommon in antiretroviral therapy-naive individuals with HIV-1 subtype A1 and D infections in Uganda. HLA genotypes A*02:01/05/14, B*44:15, and C*04:07 predicted the presence of L74I, a mutation recently observed in association with long-acting INSTI cabotegravir virologic failure. 2021 AIDS (London, England) Abstract HIV L74I 76 80 INSTI 143 148 33635845 Pre-treatment integrase inhibitor resistance is uncommon in antiretroviral therapy-naive individuals with HIV-1 subtype A1 and D infections in Uganda. Of these, two had E138T (subtype A1), three had E138E/K (subtype D), and one had T66T/I (subtype D). 2021 AIDS (London, England) Abstract HIV E138E;E138K;E138T;T66I;T66T 48;48;18;81;81 55;55;23;87;87 33635848 Drug resistance mutations in HIV provirus are associated with defective proviral genomes with hypermutation. Certain Apolipoprotein B Editing Complex 3-related DRMs including reverse transcriptase gene mutations M184I, E138K, M230I, G190E and protease gene mutations M46I, D30N were enriched in hypermutated sequences but not in intact sequences or plasma sequences. 2021 AIDS (London, England) Abstract HIV D30N;E138K;G190E;M184I;M230I;M46I 164;110;124;103;117;158 168;115;129;108;122;162 RT;PR 66;134 87;142 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. BIC also had a longer t1/2 and maintained longer antiviral activity after drug washout than DTG with the clinically relevant resistance IN mutant G140S+Q148H. 2021 Antimicrobial agents and chemotherapy Abstract HIV G140S;Q148H 146;152 151;157 IN 136 138 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Predominant NNRTIs mutations were K103N (15), Y181C (9), G190A (7), and H221Y (6) NRTIs, M184V (17), Y115F (5) and PIs, I54V (4). 2020 The Pan African medical journal Abstract HIV G190A;H221Y;I54V;K103N;M184V;Y115F;Y181C 57;72;120;34;89;101;46 62;77;124;39;94;106;51 NNRTI;NRTI;PI 12;82;115 18;87;118 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. 2021 Pathogens (Basel, Switzerland) Abstract HIV K103N;M184I;M184V;P225H 114;121;121;132 119;127;127;137 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). 2021 Pathogens (Basel, Switzerland) Abstract HIV K65R 0 4 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. INSTIs TDRM was rare, with only one primary integrase mutation E138K observed in one sample and one secondary mutation E157Q detected in another sample. 2021 Drug design, development and therapy Abstract HIV E138K;E157Q 63;119 68;124 INSTI;IN 0;44 6;53 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Two individuals harbored PIs-resistance mutations: Q58E in one patient and M46I, I54V, V82A, L10F, and Q58E mutations in another patient. 2021 Drug design, development and therapy Abstract HIV I54V;L10F;M46I;Q58E;Q58E;V82A 81;93;75;51;103;87 85;97;79;55;107;91 PI 25 28 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Two samples harbored the T215S, M184V and K70E mutations related to nucleoside RTIs (NRTIs). 2021 Drug design, development and therapy Abstract HIV K70E;M184V;T215S 42;32;25 46;37;30 RT;NRTI 79;85 83;90 33683148 Integrase Strand Transfer Inhibitor Resistance in Integrase Strand Transfer Inhibitor-Naive Persons. Two surveillance DRMs, E138K and R263K occurred in 0.15% and 0.10% of naive sequences, respectively. 2021 AIDS research and human retroviruses Abstract HIV E138K;R263K 23;33 28;38 33693680 No difference in HIV-1 integrase inhibitor resistance between CSF and blood compartments. The HIV-1 integrase sequences from CSF presented resistance mutations for 9/27 (33.3%) and 8/32 (25.0%) for ARV-naive (L74I, n = 3; L74I/M, n = 1; T97A, n = 1; E157Q, n = 4) and ARV-treated (L74I, n = 6; L74M, n = 1; T97A, n = 1; N155H, n = 1) patients, respectively. 2021 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;L74I;L74I;L74I;L74M;L74M;N155H;T97A;T97A 160;119;132;191;132;204;230;147;217 165;123;138;195;138;208;235;151;221 IN 10 19 33722682 Dolutegravir response in antiretroviral therapy naive and experienced patients with M184V/I: Impact in low-and middle-income settings. DISCUSSION: Despite high prevalence of M184V/I in antiretroviral therapy (ART) experienced patients, DTG treatment outcomes will likely not be adversely affected by this mutation. 2021 International journal of infectious diseases Abstract HIV M184I;M184V 39;39 46;46 33722682 Dolutegravir response in antiretroviral therapy naive and experienced patients with M184V/I: Impact in low-and middle-income settings. DTG-based regimens have to great extent been effective at maintaining viral suppression in treatment experienced PLWH carrying M184V/I. 2021 International journal of infectious diseases Abstract HIV M184I;M184V 127;127 134;134 33722682 Dolutegravir response in antiretroviral therapy naive and experienced patients with M184V/I: Impact in low-and middle-income settings. High genetic barrier to the development of resistance associated with DTG and progressive viral suppression in patients switched to DTG-based therapy with M184V/I, may encourage better DTG outcomes and help in curbing increasing levels of HIV drug resistance in LMICs. 2021 International journal of infectious diseases Abstract HIV M184I;M184V 155;155 162;162 33722682 Dolutegravir response in antiretroviral therapy naive and experienced patients with M184V/I: Impact in low-and middle-income settings. Lamivudine and emtricitabine associated M184V/I mutation is highly prevalent in PLWH and the majority of HIV infected individuals receiving DTG regimens may already be carrying M184V/I mutation. 2021 International journal of infectious diseases Abstract HIV M184I;M184I;M184V;M184V 40;177;40;177 47;184;47;184 HIV infections 105 117 33724373 Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial. Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). 2021 The Journal of antimicrobial chemotherapy Abstract HIV K65R;M184V 111;101 115;106 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 56;56 63;63 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. METHODS: We included vertically HIV-infected youths/young adults aged >=10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. 2021 The Journal of antimicrobial chemotherapy Abstract HIV K65E;K65N;K65R;M184I;M184V 210;210;210;195;195 218;218;218;202;202 HIV infections;HIV infections 105;32 119;44 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 34;34 41;41 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. OBJECTIVES: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. 2021 The Journal of antimicrobial chemotherapy Abstract HIV K65E;K65N;K65R;M184I;M184V 57;57;57;42;42 65;65;65;49;49 33754285 (1)H, (13)C and (15)N backbone resonance assignment of HIV-1 Gag (276-432) encompassing the C-terminal domain of the capsid protein, the spacer peptide 1 and the nucleocapsid protein. Here we report the backbone assignment of the protein CACTDW316A, M317A-SP1-NC. 2021 Biomolecular NMR assignments Abstract HIV M317A 66 71 SP1;NC 72;76 75;78 33754285 (1)H, (13)C and (15)N backbone resonance assignment of HIV-1 Gag (276-432) encompassing the C-terminal domain of the capsid protein, the spacer peptide 1 and the nucleocapsid protein. In this work, two mutations, W316A and M317A, that abolish the oligomerization of CA were introduced into the protein. 2021 Biomolecular NMR assignments Abstract HIV M317A;W316A 39;29 44;34 Capsid 82 84 33754285 (1)H, (13)C and (15)N backbone resonance assignment of HIV-1 Gag (276-432) encompassing the C-terminal domain of the capsid protein, the spacer peptide 1 and the nucleocapsid protein. The HIV-1 CACTDW316A, M317A-SP1-NC which contains the C-terminal monomeric mutant of CA, SP1 and NC was produced to study the mechanism of action of HIV-1 maturation inhibitors. 2021 Biomolecular NMR assignments Abstract HIV M317A 22 27 SP1;SP1;NC;NC;Capsid 28;89;32;97;85 31;92;34;99;87 33788308 HIV-1 subtypes and drug resistance in children during antiretroviral therapy in Brazil. The most common primary mutations found were M184V (29.5%), K103N (25%), M41L (9.8%), T215Y (8.3%), and G190A (8.3%). 2021 Journal of medical virology Abstract HIV G190A;K103N;M184V;M41L;T215Y 104;60;45;73;86 109;65;50;77;91 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. We identified the Q148HKR, G140S, Y143R, N155H, S147G, and E138EA major drug resistance mutations and the D232DN, T97TA, E157Q, G163GART accessory mutations. 2021 International journal of environmental research and public health Abstract HIV D232D;D232N;E138A;E138E;E157Q;G140S;G163A;G163G;G163R;G163T;N155H;Q148H;Q148K;Q148R;S147G;T97A;T97T;Y143R 106;106;59;59;121;27;128;128;128;128;41;18;18;18;48;114;114;34 112;112;65;65;126;32;136;136;136;136;46;25;25;25;53;119;119;39 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. Survival analysis showed an accelerated disease progression of individuals infected with HIV-1 carrying arginine or asparagine at position 8 or 157 in Nef, respectively, or the R178G Nef mutation. 2021 Viruses Abstract HIV R178G 177 182 Nef;Nef 151;183 154;186 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The 8R, 157N and R178G Nef mutations were shown to have an effect on disease progression. 2021 Viruses Abstract HIV R178G 17 22 Nef 23 26 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The majority of these Nef mutations had no significant effect on HIV-1 pathogenesis and only the 8R, 157N and R178G mutations were associated with disease course. 2021 Viruses Abstract HIV R178G 110 115 Nef 22 25 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The HIV-1 protease variants were from clinical isolates with a combination of drug resistance mutations; MUT-1 (M46I, I54V, V82A, and L10F), MUT-2 (M46I, I54V, L76V, V82A, L10F, and L33F), and MUT-3 (M46I, I54V, L76V, V82A, L90M, and F53L). 2021 Biomolecules Abstract HIV F53L;I54V;I54V;I54V;L10F;L10F;L33F;L76V;L76V;L90M;M46I;M46I;M46I;V82A;V82A;V82A 234;118;154;206;134;172;182;160;212;224;112;148;200;124;166;218 238;122;158;210;138;176;186;164;216;228;116;152;204;128;170;222 PR 10 18 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. In this study, we established such an assay and validated it using 346 primary HIV-1 isolates from patients enrolled in the Zurich Primary HIV Infection study (ZPHI) and two control viruses, HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V. 2021 Viruses Abstract HIV M184V 227 232 HIV infections 131 152 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. 2021 Viruses Abstract HIV E157Q 53 58 IN 35 44 33832362 E-pharmacophore based screening to identify potential HIV-1 gp120 and CD4 interaction blockers for wild and mutant types. Most importantly, compound NCI-254200 displayed strong communication with key residues of wild type and drug resistance single mutant gp120 (M426L and W427V) even in the dynamic condition, evidenced from MD simulation. 2021 SAR and QSAR in environmental research Abstract HIV M426L;W427V 141;151 147;156 gp120 134 139 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. On the other hand, replacing glycine at residue 10 with threonine in K3016 reduced its MI sensitivity whereas introducing glycine at SP1 10 in place of threonine in IndieC1 and ZM247 significantly enhanced their MI sensitivity. 2021 Retrovirology Abstract HIV G10T 29 65 SP1 133 136 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Serial passaging of the subtype C, K3016 virus strain in the presence of BVM analogs led to identification of two mutant viruses-Gag SP1:A1V and CA:I201V. 2021 Retrovirology Abstract HIV A1V;I201V 137;148 140;153 Capsid;Gag;SP1 145;129;133 147;132;136 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The N9S and S9N mutants had no change in MI-sensitivity. 2021 Retrovirology Abstract HIV N9S;S9N 4;12 7;15 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. While the SP1:A1V mutant was resistant to the MIs, the CA:I120V mutant displayed partial resistance and a MI-dependent phenotype. 2021 Retrovirology Abstract HIV A1V;I120V 14;58 17;63 Capsid;SP1 55;10 57;13 33844760 [Prevalence of transmitted drug resistance in HIV-infected treatment-naive patients in Chile]. The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. 2020 Revista medica de Chile Abstract HIV D67N;E138A;G190A;I84V;K101E;K103N;K70E;L210W;M184V;M41L 57;115;108;133;122;76;63;50;69;44 61;120;113;137;127;81;67;55;74;48 RT;PR 17;141 38;149 33853957 Enhancement of Antibody-Dependent Cellular Cytotoxicity and Phagocytosis in Anti-HIV-1 Human-Bovine Chimeric Broadly Neutralizing Antibodies. The bovine variable region of NC-Cow1 was paired with a human IgG1 Fc region mutated to create the following three variants: G236R/L328R (GRLR) that abrogates Fc-gamma receptor (FcgammaR) binding, and two variants that enhance binding, namely, G236A/S239D/I332E (GASDIE) and G236A/S239D/A330L/I332E (GASDALIE). 2021 Journal of virology Abstract HIV A330L;G236A;G236A;I332E;I332E;S239D;S239D;G236R;L328R 287;244;275;256;293;281;250;125;131 292;249;280;261;298;286;255;130;136 NC 30 32 33855355 Intermittent two-drug antiretroviral therapies maintain long-term viral suppression in real life in highly experienced HIV-infected patients. Resuming the same 2-DR 7 days a week led to viral resuppression in three patients, whereas the M184V mutation emerged in one patient, leading to ART modification. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M184V 95 100 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. A single amino acid mutation (T8I) in SP1 stabilizes the six-helix bundle, allowing to discern the entire CA-SP1 helix connecting to the NC domain. 2021 Communications biology Abstract HIV T8I 30 33 Capsid;NC;SP1;SP1 106;137;38;109 108;139;41;112 33880558 Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants. One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA <50 copies/mL through Week 144. 2021 The Journal of antimicrobial chemotherapy Abstract HIV G140S;Q148H 115;109 120;114 IN 124 133 33883222 Species-Specific Valid Ternary Interactions of HIV-1 Env-gp120, CD4, and CCR5 as Revealed by an Adaptive Single-Amino Acid Substitution at the V3 Loop Tip. Consistently, virions with the G310R substitution exhibited a reduced binding ability to human lymphocyte cells. 2021 Journal of virology Abstract HIV G310R 31 36 33883222 Species-Specific Valid Ternary Interactions of HIV-1 Env-gp120, CD4, and CCR5 as Revealed by an Adaptive Single-Amino Acid Substitution at the V3 Loop Tip. Furthermore, the G310R substitution influenced the gp120-CCR5 interaction in a CCR5-type dependent manner as assessed by MD simulations and an infectivity assay using exogenously expressed CCR5s. 2021 Journal of virology Abstract HIV G310R 17 22 gp120 51 56 33883222 Species-Specific Valid Ternary Interactions of HIV-1 Env-gp120, CD4, and CCR5 as Revealed by an Adaptive Single-Amino Acid Substitution at the V3 Loop Tip. Interestingly, an I198M mutation in human CCR5 restored the infectivity of the G310R virus in human cells. 2021 Journal of virology Abstract HIV G310R;I198M 79;18 84;23 33883222 Species-Specific Valid Ternary Interactions of HIV-1 Env-gp120, CD4, and CCR5 as Revealed by an Adaptive Single-Amino Acid Substitution at the V3 Loop Tip. Molecular dynamics (MD) simulations predicted that the G310R substitution at a site away from the CD4 interaction site selectively impeded the binding ability of gp120 to human CD4. 2021 Journal of virology Abstract HIV G310R 55 60 gp120 162 167 33883222 Species-Specific Valid Ternary Interactions of HIV-1 Env-gp120, CD4, and CCR5 as Revealed by an Adaptive Single-Amino Acid Substitution at the V3 Loop Tip. Virological analyses showed that a G310R substitution at the tip of the gp120 V3 loop selectively abolished the viral replication ability in human cells, despite evoking enhancement of viral replication in macaque cells. 2021 Journal of virology Abstract HIV G310R 35 40 gp120 72 77 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. CONCLUSIONS: Our analysis indicated that all RAM's that resulted in a change in the number of interactions with encompassing residues does not affect DTG binding, while accessory mutations E157Q and D232N could affect DTG binding leading to possible DTG resistance. 2021 BMC infectious diseases Abstract HIV D232N;E157Q 199;189 204;194 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Except for accessory mutant structure E157Q, only one MG contact was made with DTG, while DTG had no MG ion contacts and no DDE motif residue contacts for structure D232N. 2021 BMC infectious diseases Abstract HIV D232N;E157Q 165;38 170;43 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Of these,11.8% (34/287) of the sequences contained five different IN accessory mutations; namely Q95K, T97A, G149A, E157Q and D232N. 2021 BMC infectious diseases Abstract HIV D232N;E157Q;G149A;Q95K;T97A 126;116;109;97;103 131;121;114;101;107 IN 66 68 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. RESULTS: We observed 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) of the sequences having major INSTI RAMs: T66A, Q148H, R263K and N155H. 2021 BMC infectious diseases Abstract HIV N155H;Q148H;R263K;T66A 151;134;141;128 156;139;146;132 INSTI 116 121 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. The interaction analysis revealed that DTG bound to DNA, 2MG ions and DDE motif residues for T66A, T97A, Q148H, N155H and R263K comparable to the WT structure. 2021 BMC infectious diseases Abstract HIV N155H;Q148H;R263K;T66A;T97A 112;105;122;93;99 117;110;127;97;103 33895602 Chemical space exploration of novel naphthyl-carboxamide-diarylpyrimidine derivatives with potent anti-HIV-1 activity. Compound a1 showed exceptionally inhibitory effects with an EC50 value of 3.7 nM against HIV-1 wt strain, and an EC50 of 11 nM targeting mutant E138K. 2021 Bioorganic chemistry Abstract HIV E138K 144 149 33895602 Chemical space exploration of novel naphthyl-carboxamide-diarylpyrimidine derivatives with potent anti-HIV-1 activity. They displayed up to single-digit nanomolar activity against wild-type (WT) and rilpivirine-associated resistant mutant E138K viruses, as well as potent inhibitory ability toward the RT enzyme. 2021 Bioorganic chemistry Abstract HIV E138K 120 125 RT 183 185 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. CONCLUSIONS: In this real-world cohort, the majority of whom had virus with the M184V/I and >= 1 additional NA mutation, switching to DTG functional mono-or dual therapy with a non-cytosine NA resulted in persistent HIV-1 RNA >= 50 copies/mL in 18%. 2021 AIDS research and therapy Abstract HIV M184I;M184V 80;80 87;87 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Historical genotypes indicated that all had an M184V/I, and 23 (59%) had an M184V/I and >= 1 additional NA mutation. 2021 AIDS research and therapy Abstract HIV M184I;M184I;M184V;M184V 47;76;47;76 54;83;54;83 33952315 Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. 2021 Retrovirology Abstract HIV A83V 21 25 Gag 17 20 33965042 Near-point-of-care assay with a visual readout for detection of HIV-1 drug resistance mutations: A proof-of-concept study. Here, we present a proof-of-concept study of a rapid and simple molecular method to detect two major mutations (K103 N, Y181C) conferring resistance to first-line nonnucleoside reverse transcriptase inhibitor regimens. 2021 Talanta Abstract HIV K103N;Y181C 112;120 118;125 NNRTI 163 198 33979774 Design, synthesis and anti-HIV evaluation of novel 5-substituted diarylpyrimidine derivatives as potent HIV-1 NNRTIs. What's more, some compounds also showed low nanomole activity against some mutant strains such as K103N and E138K. 2021 Bioorganic & medicinal chemistry Abstract HIV E138K;K103N 108;98 113;103 34011540 Human Immunodeficiency Virus Type 1 Vpr Mediates Degradation of APC1, a Scaffolding Component of the Anaphase-Promoting Complex/Cyclosome. Interestingly, we found that Vpr encoded by the prototypic HIV-1 NL4.3 does not interact efficiently with APC1 and is unable to mediate its degradation as a result of a N28S-G41N amino acid substitution. 2021 Journal of virology Abstract HIV G41N;N28S 174;169 178;173 Vpr 29 32 34015097 Prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients. The overall prevalence of L74I in integrase and E138A in RT was 13.0% and 3.2%, respectively, and stable over the decade. 2021 The Journal of antimicrobial chemotherapy Abstract HIV E138A;L74I 48;26 53;30 IN;RT 34;57 43;59 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Of the 27 viraemic isolates successfully genotyped, 20 (74.1%) carried DR mutations; most frequent were M184VI (55.6%), K103N (37.1%), thymidine analog mutations (29.6%), Y181CY (22.2%). 2021 Infectious diseases Abstract HIV K103N;M184I;M184V;Y181C;Y181Y 120;104;104;171;171 125;110;110;177;177 34030114 Cantilever-centric mechanism of cooperative non-active site mutations in HIV protease: Implications for flap dynamics. The HP3 PR contained the I13V, I62V, and V77I mutations while HP4 PR contained the same mutations with the addition of the L33F mutation. 2021 Journal of molecular graphics & modelling Abstract HIV I13V;I62V;L33F;V77I 25;31;123;41 29;35;127;45 PR;PR 8;66 10;68 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. PANDAA samples were run on the ABI 7500 Sequence Detection System to genotype the K103N, V106M and M184V HIVDRMs. 2020 AAS open research Abstract HIV K103N;M184V;V106M 82;99;89 87;104;94 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Results: Sanger population sequencing and PANDAA detected K103N mutation in three (2.9%) out of 103 participants.There was no evidence of baseline V106M and M184V mutations observed in our study. 2020 AAS open research Abstract HIV K103N;M184V;V106M 58;157;147 63;162;152 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Among several mutations, M66I causes the most suppression of the GS-6207 antiviral activity (up to ~84,000-fold), and only 83- and 68-fold reductions for PF74 and ZW-1261, respectively. 2021 Viruses Abstract HIV M66I 25 29 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. To minimize the protein-ligand steric clash, the I66 side chain in the M66I-GS-6207 complex switches to a higher free energy conformation from the one adopted in the apo M66I. 2021 Viruses Abstract HIV M66I;M66I 71;170 75;174 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Among candidate NNRTI-SDRMs, six that increased in prevalence were associated with rilpivirine (E138K/Q, V179L, H221Y) or doravirine (F227C/L) resistance. 2021 Viruses Abstract HIV E138K;E138Q;F227C;F227L;H221Y;V179L 96;96;134;134;112;105 103;103;141;141;117;110 NNRTI 16 21 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Among candidate NRTI-SDRMs, there were six tenofovir-associated mutations including three which increased in prevalence (K65N, T69deletion, K70G/N/Q/T). 2021 Viruses Abstract HIV K65N;K70G;K70N;K70Q;K70T 121;140;140;140;140 125;150;150;150;150 NRTI 16 20 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Three candidate PI-SDRMs were accessory darunavir-resistance mutations (L10F, T74P, L89V). 2021 Viruses Abstract HIV L10F;L89V;T74P 72;84;78 76;88;82 PI 16 18 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. With the notable exceptions of I47A and I50L, most PI-SDRMs decreased in prevalence. 2021 Viruses Abstract HIV I47A;I50L 31;40 35;44 PI 51 53 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. 2021 International journal of molecular sciences Abstract HIV K65R 88 92 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). 2021 International journal of molecular sciences Abstract HIV K65R 105 109 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. 2021 International journal of molecular sciences Abstract HIV K65R 26 30 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). 2021 International journal of molecular sciences Abstract HIV K65R 19 23 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. 2021 International journal of molecular sciences Abstract HIV K65R 73 77 RT 78 99 34074135 Surveillance of Pretreatment Drug Resistance Among HIV-Infected Children in Ibadan, Nigeria. Three out of the four mutations were identified as non-nucleoside reverse transcriptase inhibitors DRM (K103N), whereas the fourth had nucleoside reverse transcriptase inhibitors DRM (M184V). 2021 AIDS research and human retroviruses Abstract HIV K103N;M184V 104;184 109;189 NNRTI;NRTI 51;135 87;167 34076480 Biochemical and Structural Properties of Entecavir-Resistant Hepatitis B Virus Polymerase with L180M/M204V Mutations. Crystallography of HIV RTY115F/F116Y/Q151M/F160M/M184V, mimicking HBV RT L180M/M204V, showed that the F115 bulge (F88 in HBV RT) caused by the F160M mutation induced deviated binding of dCTP from its normal tight binding position. 2021 Journal of virology Abstract HIV F116Y;F160M;M184V;Q151M;Y115F;F160M 31;43;49;37;25;143 36;48;54;42;30;148 RT;RT;RT 23;70;125 25;72;127 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). 2021 Revista espanola de quimioterapia Abstract HIV I50V;I85V;L90M;M46I 39;27;48;33 43;31;52;37 PI 14 16 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). 2021 Revista espanola de quimioterapia Abstract HIV G190A;G190E;G190S;K103N 49;49;49;28 58;58;58;33 NNRTI 12 17 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). 2021 Revista espanola de quimioterapia Abstract HIV D67G;M184I;M41L;T215I 104;157;128;77 108;162;132;82 NRTI 14 18 34090079 Exploiting the hydrophobic channel of the NNIBP: Discovery of novel diarylpyrimidines as HIV-1 NNRTIs against wild-type and K103N mutant viruses. Interestingly, few compounds displayed remarkable activity in inhibiting K103N mutant virus with EC50 values ranging from 39 nM to 1.708 microM. 2021 Bioorganic & medicinal chemistry Abstract HIV K103N 73 78 34090079 Exploiting the hydrophobic channel of the NNIBP: Discovery of novel diarylpyrimidines as HIV-1 NNRTIs against wild-type and K103N mutant viruses. Notably, FS2 (EC50(IIIB) = 16 nM, EC50(K103N) = 39 nM, SI = 294) was identified as the most significant compound, which was considerably more potent than nevirapine, lamivudine, and comparable to zidovudine. 2021 Bioorganic & medicinal chemistry Abstract HIV K103N 39 44 34107774 Drug Resistance Mutations in a Population Before Antiretroviral Therapy Initiation in Northern South Africa. The most frequent SDRMs based on drug class were; K103N (7.9%-NNRTI), K65R (2.5%-NRTI), and D30N (0.8%-PI). 2022 AIDS research and human retroviruses Abstract HIV D30N;K103N;K65R 92;50;70 96;55;74 NNRTI;NRTI;PI 62;81;103 67;85;105 34111669 Novel HIV PR inhibitors with C4-substituted bis-THF and bis-fluoro-benzyl target the two active site mutations of highly drug resistant mutant PR(S17). The substituted methoxy P2 group of 2 forms new interactions with G48V mutation, while the modified bis-fluoro-benzyl P1 group of 3 forms a halogen interaction with V82S mutation, contributing to improved inhibition of PRS17. 2021 Biochemical and biophysical research communications Abstract HIV G48V;V82S 66;165 70;169 PR 219 221 34130468 Specific synonymous mutations tightly correlate with HIV-1 co-receptor usage and differentially affect the secondary structure of HIV-1 Env RNA. Additionally, in X4-sequences, gp120 gca303gcu and gua222guc synonymous mutations are positively related to the gp120 S11R and T8A/I codons in V3 protein domain. 2021 Acta virologica Abstract HIV T8A;T8I 127;127 132;132 gp120;gp120 31;112 36;117 34132575 APOBEC3F Constitutes a Barrier to Successful Cross-Species Transmission of Simian Immunodeficiency Virus SIVsmm to Humans. Functional and mutational analyses of human- and monkey-derived alleles revealed that an R128T polymorphism in APOBEC3F contributes to species-specific counteraction by HIV-2 and SIVsmm Vifs. 2021 Journal of virology Abstract HIV R128T 89 94 Vif 186 190 34132575 APOBEC3F Constitutes a Barrier to Successful Cross-Species Transmission of Simian Immunodeficiency Virus SIVsmm to Humans. In addition, a T84S substitution in SIVsmm Vif increased its ability to counteract human APOBEC3F. 2021 Journal of virology Abstract HIV T84S 15 19 Vif 43 46 34132575 APOBEC3F Constitutes a Barrier to Successful Cross-Species Transmission of Simian Immunodeficiency Virus SIVsmm to Humans. Mutational analyses suggest that an R128T substitution in APOBEC3F and a T84S change in Vif contribute to species-specific counteraction by HIV-2 and SIVsmm. 2021 Journal of virology Abstract HIV R128T;T84S 36;73 41;77 Vif 88 91 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. Additionally, E157Q polymorphism was observed in 9.8% and L74I in 11.5% of integrase sequences. 2021 Scientific reports Abstract HIV E157Q;L74I 14;58 19;62 IN 75 84 34151963 HIV-1 non-group M phenotypic susceptibility in vitro to bictegravir and cabotegravir. Around 50% of the strains of this group naturally show a mutation (Y181C) providing them with resistance to NNRTIs and making therapeutic management more difficult. 2021 The Journal of antimicrobial chemotherapy Abstract HIV Y181C 67 72 NNRTI 108 114 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Neutralization assays against BG505.T332N variants confirmed that potent rabbit NAbs targeted previously described glycan holes on BG505 Env and accounted for a significant portion of the autologous NAb response in both the trimer and ferritin NP groups. 2021 mBio Abstract HIV T332N 36 41 Env 137 140 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Three mouse NAbs potently neutralized BG505.T332N by recognizing a glycan epitope centered in the C3/V4 region on BG505 Env, as revealed by electron microscopy (EM), X-ray crystallography, and epitope mapping. 2021 mBio Abstract HIV T332N 44 49 Env 120 123 34175948 Transmitted Drug Resistance Among Human Immunodeficiency Virus (HIV)-1 Diagnoses in the United States, 2014-2018. Continued population-level monitoring of INSTI and NRTI mutations, especially M184V and K65R, is warranted amidst expanding use of second-generation INSTIs and PrEP. 2022 Clinical infectious diseases Abstract HIV K65R;M184V 88;78 92;83 INSTI;INSTI;NRTI 41;149;51 46;155;55 34175948 Transmitted Drug Resistance Among Human Immunodeficiency Virus (HIV)-1 Diagnoses in the United States, 2014-2018. Most individual mutations had a prevalence <1.0% including M184V (0.9%) and K65R (0.1%); K103N was most prevalent (8.6%). 2022 Clinical infectious diseases Abstract HIV K103N;K65R;M184V 89;76;59 94;80;64 34175948 Transmitted Drug Resistance Among Human Immunodeficiency Virus (HIV)-1 Diagnoses in the United States, 2014-2018. TDRM prevalence did not increase or decrease significantly during 2014-2018 overall, for individual drug classes, or for key individual mutations except for M184V (12.9% increase per year; 95% confidence interval, 5.6-20.6%). 2022 Clinical infectious diseases Abstract HIV M184V 157 162 34188990 Idiopathic CD4+ Lymphocytopenia Due to Homozygous Loss of the CD4 Start Codon. Family screening showed that the patient's mother, father, and brother all had a single p.M1V mutation, allowing for deleterious effects to be partially offset by the normal copy of the gene. 2021 Cureus Abstract HIV M1V 88 93 34188990 Idiopathic CD4+ Lymphocytopenia Due to Homozygous Loss of the CD4 Start Codon. Further genetic workup revealed that in the second exon of the CD4 gene, the patient had a homozygous c.1ATG>GTG (p.Met1Val; p.M1V) mutation. 2021 Cureus Abstract HIV M1V;M1V 125;112 130;124 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. We describe a case of treatment-emergent resistance to bictegravir in a person recently diagnosed with human immunodeficiency virus who developed M184V and R263K mutations while on therapy. 2021 Open forum infectious diseases Abstract HIV M184V;R263K 146;156 151;161 34190600 Aromatic Side Chain at Position 412 of SERINC5 Exerts Restriction Activity toward HIV-1 and Other Retroviruses. A series of biochemical analyses revealed that F412A showed steady-state protein expression, localization at the cellular membrane, and incorporation into secreted virus particles to a greater extent than in the wild type. 2021 Journal of virology Abstract HIV F412A 47 52 34190600 Aromatic Side Chain at Position 412 of SERINC5 Exerts Restriction Activity toward HIV-1 and Other Retroviruses. By conducting mutagenesis analyses, we found that the substitution of phenylalanine with alanine at position 412 (F412A) resulted in a >75-fold reduction in SERINC5's restriction function. 2021 Journal of virology Abstract HIV F412A;F412A 114;70 119;112 34190600 Aromatic Side Chain at Position 412 of SERINC5 Exerts Restriction Activity toward HIV-1 and Other Retroviruses. During mutagenesis analyses, we eventually found that the single substitution of phenylalanine with alanine, but not with tyrosine or tryptophan, at position 412 (F412A) resulted in the loss of SERINC5's functions toward diverse retroviruses, whereas F412A showed steady-state protein expression, localization at the cellular membrane, and incorporation into progeny virions to a greater extent than the wild type. 2021 Journal of virology Abstract HIV F412A;F412A 163;251 168;256 34190600 Aromatic Side Chain at Position 412 of SERINC5 Exerts Restriction Activity toward HIV-1 and Other Retroviruses. Moreover, the wild-type SERINC5 restricted infection of lentiviruses pseudotyped with envelopes of murine leukemia viruses, simian immunodeficiency virus, and HIV-2, and F412A abrogated this function. 2021 Journal of virology Abstract HIV F412A 170 175 Env 86 95 34190600 Aromatic Side Chain at Position 412 of SERINC5 Exerts Restriction Activity toward HIV-1 and Other Retroviruses. The F412A substitution also resulted in the loss of SERINC5's function to sensitize HIV-1 neutralization by antibodies recognizing the envelope's membrane proximal region. 2021 Journal of virology Abstract HIV F412A 4 9 Env 135 143 34195923 Prevalence of transmitted HIV-1 drug resistance among treatment-naive individuals in China, 2000-2016. The most frequent mutation was M46L (58, 0.89%), followed by K103N (36, 0.55%), M46I (36, 0.55%), and M184V (26, 0.40%). 2021 Archives of virology Abstract HIV K103N;M184V;M46I;M46L 61;102;80;31 66;107;84;35 34195923 Prevalence of transmitted HIV-1 drug resistance among treatment-naive individuals in China, 2000-2016. While most TDR mutations were associated with reduced relative transmission fitness, mutation M46I was associated with higher relative transmission fitness than the wild-type strain. 2021 Archives of virology Abstract HIV M46I 94 98 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. 2021 Microorganisms Abstract HIV E138K;L74M;E92Q;G140S;G163R;N155H;Q148K;V151I;D64V 174;132;137;180;154;148;186;142;202 179;136;141;185;159;153;191;147;206 IN;IN;IN 81;92;218 90;94;220 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). 2021 BioMed research international Abstract HIV K103N;K103S;M184I;M184V;V82A;V82L;V82M 100;100;28;28;179;179;179 107;107;35;35;187;187;187 NNRTI;NRTI;PR;NNRTI;NRTI;PI 120;48;199;167;93;220 155;80;207;172;97;222 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). 2021 BMC infectious diseases Abstract HIV K65R 86 90 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). 2021 BMC infectious diseases Abstract HIV K65R;M184I;M184V;Y115F 26;39;39;59 30;46;46;64 34253143 Understanding the co-evolutionary molecular mechanisms of resistance in the HIV-1 Gag and protease. Although A431V was shown to coordinate several residues in PR, the L76V PR mutation was found to have a significant role in substrate recognition. 2021 Journal of biomolecular structure & dynamics Abstract HIV A431V;L76V 9;67 14;71 PR;PR 59;72 61;74 34253143 Understanding the co-evolutionary molecular mechanisms of resistance in the HIV-1 Gag and protease. Consequently, a greater binding affinity was observed when the mutated substrate was bound to an L76V-inclusive PR mutant (Gbind: -62.46 +- 5.75 kcal/mol) than without (Gbind: -50.34 +- 6.28 kcal/mol). 2021 Journal of biomolecular structure & dynamics Abstract HIV L76V 97 101 PR 112 114 34253143 Understanding the co-evolutionary molecular mechanisms of resistance in the HIV-1 Gag and protease. Here we showed that distinct changes in PR's active site, flap and elbow regions due to several PR resistance mutations (L10F, M46I, I54V, L76V, V82A) were found to alter LPV and DRV drug binding. 2021 Journal of biomolecular structure & dynamics Abstract HIV I54V;L10F;L76V;M46I;V82A 133;121;139;127;145 137;125;143;131;149 PR;PR 40;96 42;98 34253143 Understanding the co-evolutionary molecular mechanisms of resistance in the HIV-1 Gag and protease. To understand the co-evolutionary molecular mechanisms of resistance in the HIV-1 PR and Gag, we performed 100 ns molecular dynamic simulations on multidrug resistant PR's when bound to LPV, DRV or a mutated A431V NC|p1 Gag cleavage site (CS). 2021 Journal of biomolecular structure & dynamics Abstract HIV A431V 208 213 Gag;Gag;NC;PR;PR 89;220;214;82;167 92;223;216;84;169 34260070 Identification of a new 2-amino acid insertion in the integrase coding region of HIV-1 subtype G isolates. An unreported insertion of a threonine (T) and an asparagine (N) between codon 255 and 256 (S255N_TN) was identified in the IN C-terminal domain of HIV-1 subtype G isolates. 2021 Journal of medical virology Abstract HIV S255N 92 97 IN 124 126 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. The L33F mutation at the HIV-1 resistance mutation site constitutes the interconnection in the largest transmission cluster in the network. 2021 Medicine Abstract HIV L33F 4 8 34278422 Feasibility and clinical relevance of HIV-1 drug resistance testing in patients with low-level viraemia in South Africa. Major PI mutations, including M46I and V82A, were detected in 7.2% (9/125) of patients. 2021 The Journal of antimicrobial chemotherapy Abstract HIV M46I;V82A 30;39 34;43 PI 6 8 34279816 Prevalence of integrase strand transfer inhibitor (INSTIs) resistance mutations in Henan Province, China (2018-2020). The most common major resistance mutation was E138AK (0.5%, 5/999), while the most common accessory resistance mutation was E157Q (1.8%, 18/999). 2021 Infection Abstract HIV E138A;E138K;E157Q 46;46;124 52;52;129 34289404 Dual therapy with dolutegravir plus boosted protease inhibitor as maintenance or salvage therapy in highly experienced people living with HIV. The only patient (1.3%) with virological failure at Week 48 had poor adherence and baseline low-level resistance to darunavir with resistance-associated mutations at M46L, I50V and V82A. 2021 International journal of antimicrobial agents Abstract HIV I50V;M46L;V82A 172;166;181 176;170;185 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Y99H and A128T mutations at the LEDGF/p75 binding pocket render resistance to STP0404. 2021 PLoS pathogens Abstract HIV A128T;Y99H 9;0 14;4 34298060 Structural Insights into the Mechanism of Human T-cell Leukemia Virus Type 1 Gag Targeting to the Plasma Membrane for Assembly. However, G2A-Gag mutant, lacking myristoylation, is diffuse and cytoplasmic. 2021 Journal of molecular biology Abstract HIV G2A 9 12 Gag 13 16 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. In this dataset from clinical practice investigating the impact of past nucleoside reverse-transcriptase inhibitor resistance on this strategy, the combination of M184V/I plus at least 1 thymidine analog-associated mutation significantly increased the risk of VF. 2021 Open forum infectious diseases Abstract HIV M184I;M184V 163;163 170;170 NRTI 72 104 34353064 Evaluation of minor drug-resistant viral variants in patients experiencing virological failure (VF) on a first-line regimen in Fujian Province by high-throughput sequencing. RESULTS: NRTI drug resistant mutations (DRMs) were detected in a high proportion of subjects, with the most common being M184V and TAMs. 2021 Annals of palliative medicine Abstract HIV M184V 121 126 NRTI 9 13 34369051 Dolutegravir in the long term in children and adolescents: frequent virological failure but rare acquired genotypic resistance. M184V/I mutations in the reverse transcriptase gene were newly detected in three people with VF. 2021 HIV medicine Abstract HIV M184I;M184V 0;0 7;7 RT 25 46 34369051 Dolutegravir in the long term in children and adolescents: frequent virological failure but rare acquired genotypic resistance. Resistance to dolutegravir (mutations G118R and E138A in the integrase gene) emerged in one adolescent (0.7% of subjects, 2.3% of those with VF). 2021 HIV medicine Abstract HIV E138A;G118R 48;38 53;43 IN 61 70 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%). 2021 Infection and drug resistance Abstract HIV K65R;M184I;M184V;V179D;V179E 75;26;26;55;55 79;33;33;62;62 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. Overall, 32% were ciswomen, 2% transwomen, and 10% had an M184V/I mutation. 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 58;58 65;65 34402512 Distribution characteristics of drug resistance mutations of HIV CRF01_AE, CRF07_BC and CRF08_BC from patients under ART in Ganzhou, China. The most common DRMs of these three subtypes were K103N and M184V, while the mutation frequencies of M41L, D67N, K70R, K101E, V106M, Y181C, K219E, H221Y and N348I were obviously different among subtypes. 2021 The Journal of antimicrobial chemotherapy Abstract HIV D67N;H221Y;K101E;K103N;K219E;K70R;M184V;M41L;N348I;V106M;Y181C 107;147;119;50;140;113;60;101;157;126;133 111;152;124;55;145;117;65;105;162;131;138 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. Among 37 patients with viral sequences assessed by UDS, the proportion of M184V-positive DRVs significantly decreased between 2016 and 2019 (40% vs 14%, P = .005). 2022 The Journal of infectious diseases Abstract HIV M184V 74 79 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. BACKGROUND: We aimed to assess the kinetics of drug-resistant viral variants (DRVs) harboring the M184V mutation in proviral DNA of long-term virally suppressed patients, and factors associated with DRV persistence. 2022 The Journal of infectious diseases Abstract HIV M184V 98 103 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. CONCLUSIONS: While it decreased over time in HIV DNA, M184V mutation was more frequently persistent in HIV DNA of more treatment-experienced patients with longer past replication under 3TC/FTC. 2022 The Journal of infectious diseases Abstract HIV M184V 54 59 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. M184V-positive patients had a longer history of ART, lower CD4 nadir, and higher pretherapeutic HIV RNA. 2022 The Journal of infectious diseases Abstract HIV M184V 0 5 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. METHODS: Human immunodeficiency virus (HIV) DNA from blood cells stored in 2016 and 2019 was sequenced using Sanger and ultradeep sequencing (SS and UDS; detection threshold 1%) in antiretroviral therapy (ART)-treated patients with HIV RNA < 50 copies/mL for at least 5 years, with past M184V mutation documented in HIV RNA. 2022 The Journal of infectious diseases Abstract HIV M184V 287 292 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. RESULTS: Among 79 patients, by combining SS and UDS, M184V was found to be absent in 26/79 (33%) patients and persistent in 53/79 (67%). 2022 The Journal of infectious diseases Abstract HIV M184V 53 58 34415048 Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients. The persistence of M184V was associated with duration and level of HIV RNA replication under lamivudine/emtricitabine (3TC/FTC; P = .0009 and P = .009, respectively). 2022 The Journal of infectious diseases Abstract HIV M184V 19 24 34419931 Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17. These results suggest that mutation G48V contributes to drug resistance by altering the conformational dynamics of the flaps. 2021 Journal of molecular graphics & modelling Abstract HIV G48V 36 40 34419931 Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17. We have analyzed the effects of a common resistance mutation G48V in the flexible flaps of the protease by assessing the revertant PRS17V48G for changes in enzyme kinetics, inhibition, structure, and dynamics. 2021 Journal of molecular graphics & modelling Abstract HIV G48V 61 65 PR 95 103 34446677 Five Years With Dolutegravir Plus Lamivudine as a Switch Strategy: Much More Than a Positive Finding. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression <88 months. 2021 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184V;M184V 86;156 91;161 34453542 High-level resistance to bictegravir and cabotegravir in subtype A- and D-infected HIV-1 patients failing raltegravir with multiple resistance mutations. However, combinations of primary INSTI-resistance mutations such as E138A/G140A/G163R/Q148R or E138K/G140A/S147G/Q148K led to decreased susceptibility to both cabotegravir (fold change in EC50 values from 429 to 1000x) and bictegravir (60 to 100x), exhibiting a high degree of cross-resistance. 2021 The Journal of antimicrobial chemotherapy Abstract HIV E138A;E138K;G140A;G140A;G163R;Q148K;Q148R;S147G 68;95;74;101;80;113;86;107 73;100;79;106;85;118;91;112 INSTI 33 38 34453542 High-level resistance to bictegravir and cabotegravir in subtype A- and D-infected HIV-1 patients failing raltegravir with multiple resistance mutations. RESULTS: HIV-1 IN-recombinant viruses harbouring single primary mutations (N155H or Y143R/S) or in combination with secondary INSTI mutations (T97A, M50I, L74IM, E157Q, G163R or V151I) were susceptible to both bictegravir and cabotegravir. 2021 The Journal of antimicrobial chemotherapy Abstract HIV E157Q;G163R;L74I;L74M;M50I;N155H;T97A;V151I;Y143R;Y143S 162;169;155;155;149;75;143;178;84;84 167;174;160;160;153;81;147;183;91;91 INSTI;IN 126;15 131;17 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. RESULTS: We found a mutation, a threonine to isoleucine substitution at position 371 (T371I) in Gag, that restored replication competence to an IP6-binding-deficient HIV-1 mutant. 2021 Retrovirology Abstract HIV T371I;T371I 86;32 91;84 Gag 96 99 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. Of the treatment-naive participants, the two most common mutations were RT: E138A (8%) and RT: K219Q (8%). 2021 Frontiers in microbiology Abstract HIV E138A;K219Q 76;95 81;100 RT;RT 72;91 74;93 34488561 Structural effects of HIV-1 subtype C integrase mutations on the activity of integrase strand transfer inhibitors in South African patients. Interestingly, S119T and V151I were only found in patients failing raltegravir (an INSTI drug). 2021 Journal of biomolecular structure & dynamics Abstract HIV S119T;V151I 15;25 20;30 INSTI 83 88 34488561 Structural effects of HIV-1 subtype C integrase mutations on the activity of integrase strand transfer inhibitors in South African patients. Only one INSTI-treated isolate (14.28%) harboured major mutations (G140A + Q148R) as well as the E157Q minor mutation. 2021 Journal of biomolecular structure & dynamics Abstract HIV E157Q;G140A;Q148R 97;67;75 102;73;80 INSTI 9 14 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. 2021 Virology journal Abstract HIV K103N 121 126 34496571 Structure-Based Design and Discovery of Pyridyl-Bearing Fused Bicyclic HIV-1 Inhibitors: Synthesis, Biological Characterization, and Molecular Modeling Studies. Furthermore, molecular modeling studies elucidated the binding modes of compounds 6, 15, 21, and 30 in the binding pocket of WT, E138K, K103N, or Y181C HIV-1 RTs. 2021 Journal of medicinal chemistry Abstract HIV E138K;K103N;Y181C 129;136;146 134;141;151 RT 158 161 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. A novel EFdA resistance mutational pattern that included A114S was identified in the background of M184V. 2021 Antimicrobial agents and chemotherapy Abstract HIV A114S;M184V 57;99 62;104 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. A114S/M184V exhibited higher EFdA resistance (~24-fold) than either M184V (~8-fold) or A114S alone (~2-fold). 2021 Antimicrobial agents and chemotherapy Abstract HIV A114S;A114S;M184V;M184V 87;0;6;68 92;5;11;73 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. Biochemical experiments confirmed decreases in the enzymatic efficiency (kcat/Km) of WT versus A114S (2.1-fold) and A114S/M184V/A502V (6.5-fold) RTs, with no effect of A502V on enzymatic efficiency or specific infectivity. 2021 Antimicrobial agents and chemotherapy Abstract HIV A114S;A502V;M184V;A114S;A502V 116;128;122;95;168 121;133;127;100;173 RT 145 148 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. Regardless of the starting viral sequence, all selected EFdA-resistant variants included the M184V reverse transcriptase (RT) mutation. 2021 Antimicrobial agents and chemotherapy Abstract HIV M184V 93 98 RT;RT 99;122 120;124 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. Remarkably, A114S/M184V and A114S/M184V/A502V resistance mutations were up to 50-fold more sensitive to tenofovir than was WT HIV-1. 2021 Antimicrobial agents and chemotherapy Abstract HIV A114S;A502V;M184V;A114S;M184V 28;40;34;12;18 33;45;39;17;23 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. The rather modest EFdA resistance of M184V or A114S/M184V (8- and 24-fold), their hypersusceptibility to tenofovir, and strong published in vitro and in vivo data suggest that EFdA is an excellent therapeutic candidate for naive, AZT-, FTC/3TC-, and especially tenofovir-treated patients. 2021 Antimicrobial agents and chemotherapy Abstract HIV A114S;M184V;M184V 46;52;37 51;57;42 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. To study EFdA resistance patterns that may emerge in naive or tenofovir (TFV)-, emtricitabine/lamivudine (FTC/3TC)-, or zidovudine (AZT)-treated patients, we performed viral passaging experiments starting with WT, K65R, M184V, or D67N/K70R/T215F/K219Q HIV-1. 2021 Antimicrobial agents and chemotherapy Abstract HIV D67N;K219Q;K70R;T215F;K65R;M184V 230;246;235;240;214;220 234;251;239;245;218;225 34516245 Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains. Using recombinant viruses, we validated the role for M184V as the primary determinant of EFdA resistance; none of the observed connection subdomain (R358K and E399K) or RNase H domain (A502V) mutations significantly contributed to EFdA resistance. 2021 Antimicrobial agents and chemotherapy Abstract HIV A502V;E399K;M184V;R358K 185;159;53;149 190;164;58;155 34523753 Changes in dynamic and static structures of the HIV-1 p24 capsid protein N-domain caused by amino-acid substitution are associated with its viral viability. In addition, the presence of fewer helical structures was observed in M68T and P90T, beyond the broad area from helix 1 to the C-terminal part of helix 4. 2021 Protein science Abstract HIV M68T;P90T 70;79 74;83 34523753 Changes in dynamic and static structures of the HIV-1 p24 capsid protein N-domain caused by amino-acid substitution are associated with its viral viability. Next, compared with P90T, we examined cis-conformation or trans-conformation of wild-type adopted by isomerization at G89-P90. 2021 Protein science Abstract HIV P90T 20 24 34523753 Changes in dynamic and static structures of the HIV-1 p24 capsid protein N-domain caused by amino-acid substitution are associated with its viral viability. Since P90T mutant adopts only a trans-conformation, comparison of chemical shifts and signal intensities between each spectra revealed that the major peaks (about 85%) in the spectrum of wild-type correspond to trans-conformation. 2021 Protein science Abstract HIV P90T 6 10 34523753 Changes in dynamic and static structures of the HIV-1 p24 capsid protein N-domain caused by amino-acid substitution are associated with its viral viability. This is because HIV-1 with a P90T protein, which adopts only a trans-conformation, is associated with non-viability of biological activity. 2021 Protein science Abstract HIV P90T 29 33 34523753 Changes in dynamic and static structures of the HIV-1 p24 capsid protein N-domain caused by amino-acid substitution are associated with its viral viability. Three p24 mutants with amino acid substitutions in capsid N-terminal domain protein were examined: G60W (alpha3-4 loop), M68T (helix 4), and P90T (alpha4-5 loop), which exhibited no viability for biological activity. 2021 Protein science Abstract HIV G60W;M68T;P90T 99;121;141 103;125;145 Capsid;p24 51;6 57;9 34523971 Natural Occurring Polymorphisms in HIV-1 Integrase and RNase H Regulate Viral Release and Autoprocessing. An HIV variant containing a Met-to-Ile change at codon 50 in integrase [HIV(IN:M50I)] was found as an impaired virus. 2021 Journal of virology Abstract HIV M50I;M50I 79;28 83;57 IN;IN 61;76 70;78 34523971 Natural Occurring Polymorphisms in HIV-1 Integrase and RNase H Regulate Viral Release and Autoprocessing. Here, during the evaluation of the roles of naturally emerging nonsynonymous SNPs in HIV RNA, we found that autoprocessing is inhibited by Met-to-Ile change at codon 50 in integrase GagPol. 2021 Journal of virology Abstract HIV M50I 139 168 IN;IN 182;172 188;181 34523971 Natural Occurring Polymorphisms in HIV-1 Integrase and RNase H Regulate Viral Release and Autoprocessing. Other coexisting SNPs, Ser-to-Asn change at codon 17 in integrase or Asn-to-Ser mutation at codon 79 in RNase H, recovered this defect, suggesting that autoprocessing is regulated by not only integrase but also RNase H in GagPol polyprotein. 2021 Journal of virology Abstract HIV N79S;S17N 69;23 100;52 IN;IN;GagPol 56;192;222 65;201;228 34523971 Natural Occurring Polymorphisms in HIV-1 Integrase and RNase H Regulate Viral Release and Autoprocessing. The impaired maturation and replication were rescued by two other VL-associated SNPs, Ser-to-Asn change at codon 17 of integrase and Asn-to-Ser change at codon 79 of RNase H. 2021 Journal of virology Abstract HIV N79S;S17N 133;86 162;115 IN 119 128 34523971 Natural Occurring Polymorphisms in HIV-1 Integrase and RNase H Regulate Viral Release and Autoprocessing. Western blot analysis demonstrated a defect in autoprocessing of GagPol and Gag polyproteins' autoprocessing in the HIV(IN:M50I) particles, although Forster resonance energy transfer (FRET) assay displayed that GagPol containing IN:M50I forms a homodimer with a similar efficiency with GagPol (wild type). 2021 Journal of virology Abstract HIV M50I;M50I 123;232 127;236 Gag;IN;GagPol;GagPol;GagPol;IN 76;120;65;211;286;229 79;122;71;217;292;231 34534138 Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection. One DTG + 3TC participant who did not meet CVW criteria developed M184V at week 132 and R263R/K at week 144, conferring a 1.8-fold change in susceptibility to DTG; non-adherence to therapy was reported. 2022 AIDS (London, England) Abstract HIV M184V;R263K;R263R 66;88;88 71;95;95 34536931 Design, synthesis, and antiviral evaluation of novel piperidine-substituted arylpyrimidines as HIV-1 NNRTIs by exploring the hydrophobic channel of NNIBP. In addition, most of the compounds displayed micromolar activity against K103N and E138K mutant strains, while FT1 (EC50(K103N) = 50 nM, EC50(E138K) = 0.19 microM) still has the most effective activity. 2021 Bioorganic chemistry Abstract HIV E138K;K103N;E138K;K103N 83;73;142;121 88;78;147;126 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. From a panel of mutants, we identified three with increased capsid stability in cells and found that, whilst the M68C/E212C mutant had a 5-fold reduction in reverse transcription, two mutants, A14C/E45C and E180C, were able to reverse transcribe to approximately WT levels in cycling cells. 2021 PLoS pathogens Abstract HIV A14C;E180C;E212C;E45C;M68C 193;207;118;198;113 197;212;123;202;117 RT;Capsid 157;60 178;66 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Furthermore, we observed A14C/E45C mutant capsid in nuclear and chromatin-associated fractions implying that the hyper-stable cores themselves entered the nucleus. 2021 PLoS pathogens Abstract HIV A14C;E45C 25;30 29;34 Capsid 42 48 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Immunofluorescence studies revealed that although the A14C/E45C mutant capsid reached the nuclear pore with the same kinetics as wild type capsid, it was then retained at the pore in association with Nup153. 2021 PLoS pathogens Abstract HIV A14C;E45C 54;59 58;63 Capsid;Capsid 71;139 77;145 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. The most prevalent shared DRMs included V106I (45.35%), V179D (15.1%), and V179E (15.1%). 2021 Frontiers in genetics Abstract HIV V106I;V179D;V179E 40;56;75 45;61;80 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). 2021 Genes Abstract HIV K103N;M184V;T215F;T215Y;V108I;Y181C;Y181I;Y181V 84;58;140;140;172;110;110;110 89;63;147;147;177;119;119;119 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). 2021 Genes Abstract HIV K103N;K219E;K219N;K219Q;K219R;M184V;P225H;Y181C;Y181I;Y181V 50;156;156;156;156;75;128;100;100;100 55;167;167;167;167;80;133;109;109;109 34576162 TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding. These results show that the refolding of R52A Tat was stimulated well at a 0.3 muM TAR RNA concentration; wild-type Tat refolding was essentially abolished because of a reduction in the affinity for TAR RNA at that con centration. 2021 International journal of molecular sciences Abstract HIV R52A 41 45 Tat;Tat 46;116 49;119 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Cell-cell transfer experiments conducted with the Env endocytosis mutant (Y712A) showed increased transfer of Env. 2021 Viruses Abstract HIV Y712A 74 79 Env;Env 50;110 53;113 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. This Y712A Env mutant also exhibited an altered Gag/biotin Env fluorescence ratio during transfer that correlated with decreased productive cell-to-cell infection. 2021 Viruses Abstract HIV Y712A 5 10 Env;Env;Gag 11;59;48 14;62;51 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. Out of 17 new mutations, 14 resulted in virologic failure and included NRTIs (L74I, L74V, T69D, V65R); NNRTIs (A98G, V179E, V179F, V179D, 179F); PIs (I54V3, F53L2, L89T, G48A). 2021 The Pan African medical journal Abstract HIV A98G;G48A;L74I;L74V;L89T;T69D;V179D;V179E;V179F;V65R 111;170;78;84;164;90;131;117;124;96 115;174;82;88;168;94;136;122;129;100 NNRTI;NRTI;PI 103;71;145 109;76;148 34609269 Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. A unique mutation observed frequently in patients treated with nelfinavir is D30N as it is selected exclusively by nelfinavir. 2021 Journal of biomolecular structure & dynamics Abstract HIV D30N 77 81 34609269 Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. D30N mutation also significantly reduces cleavage activity of HIV-1 protease and affects viral fitness. 2021 Journal of biomolecular structure & dynamics Abstract HIV D30N 0 4 PR 68 76 34609269 Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. Here, we have determined crystal structures of D30N HIV-1 protease in unliganded form and in complex with nelfinavir. 2021 Journal of biomolecular structure & dynamics Abstract HIV D30N 47 51 PR 58 66 34609269 Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. The D30N mutation imparts very high resistance to nelfinavir but unlike other primary mutations does not give cross-resistance to the majority of other drugs. 2021 Journal of biomolecular structure & dynamics Abstract HIV D30N 4 8 34609269 Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. The decreased catalytic activity of D30N HIV-1 protease due to altered interaction with the substrates and reduced stability of folding core may be the reason for the reduced replicative capacity of the virus harboring mutant HIV-1 protease.Communicated by Ramaswamy H. 2021 Journal of biomolecular structure & dynamics Abstract HIV D30N 36 40 PR;PR 47;232 55;240 34609269 Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease. These structures provide the rationale for reduced cleavage activity and the molecular basis of drug resistance induced by D30N mutation. 2021 Journal of biomolecular structure & dynamics Abstract HIV D30N 123 127 34622550 Characterization of HIV-1 drug resistance among patients with failure of second-line combined antiretroviral therapy in central Ethiopia. Most common mutations were M184V (57.1%), Y188C (25.7%), M46I/L (25.7%) and V82A/M (25.7%). 2022 HIV medicine Abstract HIV M184V;M46I;M46L;V82A;V82M;Y188C 27;57;57;76;76;42 32;63;63;82;82;47 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. NRTI primary mutations M184 V/I and K65R/E/N were found in 28.8% and 8.9% of subjects respectively, while NNRTI primary mutations K103N/S, G190A, and Y181C were found in 21.0%, 14.6%, and 10.9% of subjects. 2021 Medicine Abstract HIV G190A;K103N;K103S;K65E;K65N;K65R;M184I;M184V;Y181C 139;130;130;36;36;36;23;23;150 144;137;137;44;44;44;31;31;155 NNRTI;NRTI 106;0 111;4 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Only one exhibited reduced susceptibility to TMR and it contained an M426L polymorphism. 2022 AIDS (London, England) Abstract HIV M426L 69 74 34651192 Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). 2021 The Journal of antimicrobial chemotherapy Abstract HIV E138K;E138K;K101E;N155H 96;124;130;149 101;129;135;154 INSTI;NNRTI;NNRTI 158;105;139 163;110;144 34652967 HIV-1 Drug Resistance Among Treatment-Naive Transgenders from India. Mutations M184V, A98G, K103N, G190A, and Y318F associated with resistance to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitors were observed. 2021 AIDS research and human retroviruses Abstract HIV A98G;G190A;K103N;M184V;Y318F 17;30;23;10;41 21;35;28;15;46 NNRTI;NRTI 124;77 160;109 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. One patient had a viral rebound associated with emergence of an F227C reverse transcriptase variant (per chain-termination method sequencing) 14 days postdose; this variant was found in a second participant by ultra-deep sequencing as an emerging minority variant. 2022 Journal of acquired immune deficiency syndromes (1999) Abstract HIV F227C 64 69 RT 70 91 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. HIV-1 p24 and viral load assays were used to verify the biological activity of AnkGAG1D4 and AnkGAG1D4-S45Y as assembly inhibitors. 2021 Biomolecules Abstract HIV S45Y 103 107 p24 6 9 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. However, the intracellular anti-HIV-1 activity of AnkGAG1D4-S45Y has not yet been validated. 2021 Biomolecules Abstract HIV S45Y 60 64 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. In this study, the performance of AnkGAG1D4 and AnkGAG1D4-S45Y in inhibiting wild-type HIV-1 and HIV-1 maturation inhibitor-resistant replication in SupT1 cells was evaluated. 2021 Biomolecules Abstract HIV S45Y 58 62 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. The present data show that the potency of AnkGAG1D4-S45Y was superior to AnkGAG1D4 in interrupting either HIV-1 wild-type or the HIV maturation inhibitor-resistant strain. 2021 Biomolecules Abstract HIV S45Y 52 56 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G118R or R263K increased the rate of dolutegravir dissociation from integrase-DNA complexes versus wild-type but retained prolonged binding. 2022 Antimicrobial agents and chemotherapy Abstract HIV R263K;G118R 9;0 14;5 IN 68 77 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Of participants who received dolutegravir through week 48 plus an additional 110 weeks for this assessment, 6 met CVW criteria with treatment-emergent INSTI resistance-associated substitutions and 1 had R263R/K at baseline but not at CVW. 2022 Antimicrobial agents and chemotherapy Abstract HIV R263K;R263R 203;203 210;210 INSTI 151 156 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Treatment-emergent G118R was detected in 5 participants, occurring with >=2 other integrase substitutions, including R263R/K, in 3 participants and without other integrase substitutions in 2 participants. 2022 Antimicrobial agents and chemotherapy Abstract HIV G118R;R263K;R263R 19;117;117 24;124;124 IN;IN 82;162 91;171 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Continuing evolution after R263K acquisition led to reduced dolutegravir susceptibility and integrase replication capacity. 2022 Antimicrobial agents and chemotherapy Abstract HIV R263K 27 32 IN 92 101 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. G118R and R263K INSTI resistance substitutions, which are distinct to second-generation INSTIs, were detected in adolescents and children with prior virologic failure who received dolutegravir. 2022 Antimicrobial agents and chemotherapy Abstract HIV R263K;G118R 10;0 15;5 INSTI;INSTI 16;88 21;94 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. G118R reduced dolutegravir susceptibility and integrase replication capacity more than R263K and demonstrated greater reduction in susceptibility and integrase replication capacity when present with specific secondary integrase substitutions, including L74M, T66I, and E138E/K. 2022 Antimicrobial agents and chemotherapy Abstract HIV E138E;E138K;L74M;R263K;T66I;G118R 269;269;253;87;259;0 276;276;257;92;263;5 IN;IN;IN 46;150;218 55;159;227 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Structural examination revealed potential mechanisms for G118R- and R263K-mediated INSTI resistance. 2022 Antimicrobial agents and chemotherapy Abstract HIV G118R;R263K 57;68 62;73 INSTI 83 88 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The on-study secondary integrase substitution E157Q or L74I was observed in 2 participants. 2022 Antimicrobial agents and chemotherapy Abstract HIV E157Q;L74I 46;55 51;59 IN 23 32 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The rare INSTI resistance-associated substitution G118R or R263K developed in 6 participants. 2022 Antimicrobial agents and chemotherapy Abstract HIV G118R;R263K 50;59 55;64 INSTI 9 14 34696351 The Zinc Content of HIV-1 NCp7 Affects Its Selectivity for Packaging Signal and Affinity for Stem-Loop 3. Compared to NCp7, 2NCp7 exhibited a much higher Psi-selectivity and SL3-affinity, similar to Gag, whereas 0NCp7 exhibited a lower Psi-selectivity and SL3-affinity, similar to the H23&H44K double mutant of NCp7, indicating that the different RNA-binding property of Gag NC domain and the mature NCp7 may be resulted, at least partially, from their different zinc content. 2021 Viruses Abstract HIV H44K 183 187 Gag;Gag;NC;NC;NC;NC 93;265;12;205;269;294 96;268;14;207;271;296 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Two nonsynonymous mutations (N170D and R267K) were associated with increased levels of immediate early protein 1 (IE-1) and glycoprotein B (gB) HCMV-reactive antibodies, suggesting a higher viral burden. 2021 Microbiology spectrum Abstract HIV N170D;R267K 29;39 35;44 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. The prevalence of TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) is higher than that of other inhibitors, with a relatively high prevalence of three mutations [V179D/E/DE (4.93%), K103N/KN (3.11%), and E138A/G (1.52%)]. 2021 Frontiers in public health Abstract HIV E138A;E138G;K103K;K103N;V179D;V179E 220;220;198;198;178;178 227;227;205;205;188;188 NNRTI;NNRTI 26;75 62;81 34714124 HIV-1 Genetic Diversity and Natural Polymorphisms of the Integrase Gene in Integrase Inhibitor-Naive Patients in Harare, Zimbabwe. No major INSTI resistance mutations were detected; however, the L74I polymorphism was detected in three sequences of the 44 (6.8%). 2021 AIDS research and human retroviruses Abstract HIV L74I 64 68 INSTI 9 14 34714124 HIV-1 Genetic Diversity and Natural Polymorphisms of the Integrase Gene in Integrase Inhibitor-Naive Patients in Harare, Zimbabwe. The subtype C consensus was identical to the global subtype C consensus and varied from the global subtype B consensus at five major positions: T124A, V201I, T218I, D278A, and S283G. 2021 AIDS research and human retroviruses Abstract HIV D278A;S283G;T124A;T218I;V201I 165;176;144;158;151 170;181;149;163;156 34740228 Doravirine: its role in HIV treatment. Doravirine has a high genetic barrier to resistance with retained activity in the presence of single NNRTI mutations K103N, Y181C and G190A. 2022 Current opinion in HIV and AIDS Abstract HIV G190A;K103N;Y181C 134;117;124 139;122;129 NNRTI 101 106 34741606 In vitro analysis of the replicative capacity and phenotypic susceptibility to integrase inhibitors of HIV-2 mutants with integrase insertions. A 231ins GK SDM was resistant to raltegravir and cabotegravir, but remained susceptible to dolutegravir and bictegravir. 2022 The Journal of antimicrobial chemotherapy Abstract HIV 231ins GK 2 11 34741606 In vitro analysis of the replicative capacity and phenotypic susceptibility to integrase inhibitors of HIV-2 mutants with integrase insertions. BACKGROUND: HIV-2 resistance to integrase strand-transfer inhibitors (INSTIs) is characterized by two main pathways: (i) mutations at codons 143, 148 and155; and (ii) amino acid insertion after integrase codon 231 (231ins). 2022 The Journal of antimicrobial chemotherapy Abstract HIV 231ins 215 221 IN;IN;INSTI 32;194;70 41;203;76 34741606 In vitro analysis of the replicative capacity and phenotypic susceptibility to integrase inhibitors of HIV-2 mutants with integrase insertions. CONCLUSIONS: These first data on the newly described resistance pathway 231ins, using site-directed mutagenesis, showed no measurable impact on viral fitness and confirmed the decreased susceptibility to a first-generation INSTI (raltegravir) and cabotegravir. 2022 The Journal of antimicrobial chemotherapy Abstract HIV 231ins 72 78 INSTI 223 228 34741606 In vitro analysis of the replicative capacity and phenotypic susceptibility to integrase inhibitors of HIV-2 mutants with integrase insertions. Resistance to second-generation INSTIs (dolutegravir and bictegravir) occurred for mutants with a 5 amino acid 231ins. 2022 The Journal of antimicrobial chemotherapy Abstract HIV 231ins 111 117 INSTI 32 38 34741606 In vitro analysis of the replicative capacity and phenotypic susceptibility to integrase inhibitors of HIV-2 mutants with integrase insertions. RESULTS: Viruses bearing 231ins did not present impaired replicative capacity, except the 231ins GIRGK mutant. 2022 The Journal of antimicrobial chemotherapy Abstract HIV 231ins;231ins GIRGK 25;90 31;102 34741606 In vitro analysis of the replicative capacity and phenotypic susceptibility to integrase inhibitors of HIV-2 mutants with integrase insertions. The SDM with T97A+N155H, with or without E92Q, was resistant to all INSTIs, except bictegravir. 2022 The Journal of antimicrobial chemotherapy Abstract HIV E92Q;N155H;T97A 41;18;13 45;23;17 INSTI 68 74 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and >=3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). 2022 The Journal of antimicrobial chemotherapy Abstract HIV K65R 0 4 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Overall, 18/168 (11%) had NNRTI mutations including K101E, K103N/S, V106M, V108I, E138A/G, V179D/I/T and H221Y. 2021 Journal of the International AIDS Society Abstract HIV E138A;E138G;H221Y;K101E;K103N;K103S;V106M;V108I;V179D;V179I;V179T 82;82;105;52;59;59;68;75;91;91;91 89;89;110;57;66;66;73;80;100;100;100 NNRTI 26 31 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The E138A mutation was detected in both the DPV (3 of 71 [4.2%]) and PLB arm (5 of 97 [5.2%]) and conferred modest reductions in DPV susceptibility in some reverse transcriptase backgrounds but not others. 2021 Journal of the International AIDS Society Abstract HIV E138A 4 9 RT 156 177 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In resistance studies, the previously identified A364V Gag region mutation was selected under MI pressure in cell culture and during the phase IIa clinical study. 2022 Antimicrobial agents and chemotherapy Abstract HIV A364V 49 54 Gag 55 58 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Virus-like particles containing the A364V mutation exhibited a p25 cleavage rate 9.3 times higher than wild-type particles, providing a possible mechanism for MI resistance. 2022 Antimicrobial agents and chemotherapy Abstract HIV A364V 36 41 34787532 Investigating potency of TMC-126 against wild-type and mutant variants of HIV-1 protease: a molecular dynamics and free energy study. Our study reveals that the flap of PR1 adopts a semi-open conformation due to the mutation I50V or MDR20. 2021 SAR and QSAR in environmental research Abstract HIV I50V 91 95 PR 35 38 34787532 Investigating potency of TMC-126 against wild-type and mutant variants of HIV-1 protease: a molecular dynamics and free energy study. The potency of the inhibitor decreases in the order: wild type PR1 > M46L > MDR20 > I50V > PR2 > V32I > A28S. 2021 SAR and QSAR in environmental research Abstract HIV A28S;I50V;M46L;V32I 104;84;69;97 108;88;73;101 PR;PR 91;63 94;66 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). The performance of the PANDAA assay in screening K65R, K103NS, M184VI, Y181C, and G190A mutations compared to the reference assay, Sanger sequencing was evaluated by Cohen s kappa coefficient on Stata version 14 (StataCorp LP, College Station, TX, USA). 2021 The Pan African medical journal Abstract HIV G190A;K103N;K103S;K65R;M184I;M184V;Y181C 82;55;55;49;63;63;71 87;61;61;53;69;69;76 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). We assessed the performance of a rapid HIV-1 drug resistance assay, the Pan Degenerate Amplification and Adaptation (PANDAA) assay when screening for significant HIV-1 drug resistance mutations (DRMs) such as K65R, K103NS, M184VI, Y181C and G190A. 2021 The Pan African medical journal Abstract HIV G190A;K103N;K103S;K65R;M184I;M184V;Y181C 241;215;215;209;223;223;231 246;221;221;213;229;229;236 34802406 Diversity of HIV-1 Subtypes and Transmitted Drug-resistance Mutations Among Minority HIV-1 Variants in a Turkish Cohort. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates. 2022 Current HIV research Abstract HIV K65R 18 22 34802406 Diversity of HIV-1 Subtypes and Transmitted Drug-resistance Mutations Among Minority HIV-1 Variants in a Turkish Cohort. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. 2022 Current HIV research Abstract HIV I54V;I84V;K103N;K65R;L24I;L74I;L90M;M184I;M184V;M46I;N83D;V82A;M41L 108;84;52;12;96;6;102;29;18;78;72;90;0 112;88;57;16;100;10;106;34;23;82;76;94;4 NNRTI;NRTI;PI 61;46;120 66;50;122 34802406 Diversity of HIV-1 Subtypes and Transmitted Drug-resistance Mutations Among Minority HIV-1 Variants in a Turkish Cohort. Most mutations were found in low-abundance (frequency range: 1.0 % - 4.7 %) HIV-1 variants, except M41L and K103N. 2022 Current HIV research Abstract HIV K103N;M41L 108;99 113;103 34814456 [HIV-1 drug resistance and subtypes in newly reported HIV/AIDS patients before antiretroviral therapy in Taizhou city, 2016-2018]. The resistance mutations of NNRTIs and NRTIs were mainly K103 N (0.7%) and M184I/V (0.5%). 2021 Zhonghua liu xing bing xue za zhi Abstract HIV K103N;M184I;M184V 57;75;75 63;82;82 NNRTI;NRTI 28;39 34;44 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Among NRTI resistance mutations, M184V (73.2%), K219Q (63.4%) and T215 (56.1%) complex were the most mutated positions, while the most common NNRTI resistance mutations were K103N (24.4%), K101E, P225H and V108I 7.5% each. 2021 Infection and drug resistance Abstract HIV K101E;K103N;K219Q;M184V;P225H;V108I 189;174;48;33;196;206 194;179;53;38;201;211 NNRTI;NRTI 142;6 147;10 34826702 Characterization of the membrane penetration-enhancing peptide S19 derived from human syncytin-1 for the intracellular delivery of TAT-fused proteins. In a secondary structure analysis of the mutated S19-TAT peptides in the presence of liposomes mimicking late endosomes (LEs), the CD spectra of V3A and I4A mutants with low uptake activity showed the appearance of an alpha-helix structure, whereas the mutant G5A retained both the uptake activity and the beta-structure. 2022 Biochemical and biophysical research communications Abstract HIV G5A;I4A;V3A 260;153;145 263;156;148 Tat 53 56 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Comparing the sequences of the 14 viruses with that of the defective virus illustrated that only Val-to-Ile change at codon 151 of IN (IN:V151I) existed in the recombinant virus. 2021 Viruses Abstract HIV V151I;V151I 138;97 143;127 IN;IN 131;135 133;137 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. The coexisting Ser-to-Asn change at codon 17 of IN or Asn-to-Ser mutation at codon 79 of RNaseH (RH) compensated the defective IN:M50I phenotype, suggesting that both IN and RH regulate an HIV infectability. 2021 Viruses Abstract HIV M50I;N79S;S17N 130;54;15 134;85;44 IN;IN;IN 48;127;167 50;129;169 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. The result demonstrated that 14 plasma HIVs contained IN:M50I without the compensatory mutations. 2021 Viruses Abstract HIV M50I 57 61 IN 54 56 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. These results demonstrate that a combination of IN:M50I and IN:V151I mutations, but not IN:M50I alone, produces a defective virus. 2021 Viruses Abstract HIV M50I;M50I;V151I 51;91;63 55;95;68 IN;IN;IN 48;60;88 50;62;90 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. This IN:V151I is known as a polymorphic mutation and was derived from HIVNL4.3 backbone. 2021 Viruses Abstract HIV V151I 8 13 IN 5 7 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We have recently reported that a recombinant HIV-1NL4.3 containing Met-to-Ile change at codon 50 of integrase (IN) (IN:M50I) exhibits suppression of the virus release below 0.5% of WT HIV, and the released viral particles are replication-incompetent due to defects in Gag/GagPol processing by inhibition of the initiation of autoprocessing of GagPol polyproteins in the virions and leads to replication-incompetent viruses. 2021 Viruses Abstract HIV M50I;M50I 119;67 123;96 IN;Gag;IN;IN 100;268;111;116 109;271;113;118 34849981 Virological outcomes with dolutegravir plus either lamivudine or two NRTIs as switch strategies: a multi-cohort study. CONCLUSIONS: Lamivudine/dolutegravir maintenance DT showed similar efficacy to dolutegravir-based TT; however, past M184V/I may favour VF. 2022 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 116;116 123;123 34849981 Virological outcomes with dolutegravir plus either lamivudine or two NRTIs as switch strategies: a multi-cohort study. Conversely, in the setting of pre-existing M184V/I, DT showed a trend to increased risk of VF (versus tenofovir-based TT, aHR = 137.50, 95% CI = 4.24-4464.06; versus abacavir-based TT, aHR = 33.88, 95% CI = 1.75-656.47). 2022 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 43;43 50;50 34851643 Multiple Molecular Dynamics Simulations and Free-Energy Predictions Uncover the Susceptibility of Variants of HIV-1 Protease against Inhibitors Darunavir and KNI-1657. Focused on the complexes of wild type (WT) PR and two mutant PRs (V32I/L33F/I54M/V82I and V32I/L33F/I54M/I84 V) with inhibitors Darunavir (DRV) and KNI-1657 (KNI), respectively, we have conducted research on the conformational dynamics and the resistance mechanism caused by residue mutations through multiple molecular dynamics (MD) simulations combined with an energy (MM-PBSA and solvated interaction energy (SIE)) prediction. 2021 Langmuir Abstract HIV V32I;I54M;I54M;L33F;L33F;V32I;V82I 66;76;100;95;71;90;81 70;80;104;99;75;94;85 PR;PR 43;61 45;64 34871089 Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. Through week 240, 16/32 participants (50.0%) experienced virologic failure, including seven who developed treatment-emergent RPV resistance-associated mutations (RAMs [frequently E138K]): all 7 had >=1 treatment-emergent NRTI RAM. 2022 Antimicrobial agents and chemotherapy Abstract HIV E138K 179 184 NRTI 221 225 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. DISCUSSION: Rapid PrEP intensification to ART allowed to achieve high rates of HIV viral suppression despite significant rates of M184V mutation harboured in those newly diagnosed with HIV and reporting recent PrEP exposure. 2022 AIDS (London, England) Abstract HIV M184V 130 135 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. M184V mutation was harboured more commonly in the recent PrEP use group (30% vs. 2022 AIDS (London, England) Abstract HIV M184V 0 5 34890994 Indolylarylsulfones bearing phenylboronic acid and phenylboronate ester functionalities as potent HIV1 non-nucleoside reverse transcriptase inhibitors. Notably, (3-ethylphenyl)boronic acid substituted indole-2-carboxamide maintained excellent activities against the single HIV-1 mutants L100I (EC50 = 7.3 nM), K103N (EC50 = 9.2 nM), as well as the double mutant V106A/F227L (EC50 = 21.1 nM). 2022 Bioorganic & medicinal chemistry Abstract HIV F227L;K103N;L100I;V106A 216;158;135;210 221;163;140;215 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Most of the participants (n = 19) were virologically suppressed at baseline and had one primary INSTI-R substitution, E92G, Y143C/H, S147G, Q148H/K/R, N155S, or R263K, +/-secondary substitutions. 2022 Journal of acquired immune deficiency syndromes (1999) Abstract HIV E92G;N155S;Q148H;Q148K;Q148R;R263K;S147G;Y143C;Y143H 118;151;140;140;140;161;133;124;124 122;156;149;149;149;166;138;131;131 INSTI 96 101 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. One treatment-naive participant had virus with Q148H+G140S that was fully sensitive to bictegravir but only partially to dolutegravir (phenotype <2.5-fold change and >4-fold change, respectively). 2022 Journal of acquired immune deficiency syndromes (1999) Abstract HIV G140S;Q148H 53;47 58;52 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), including in patients with M184V/I substitutions. 2022 Journal of acquired immune deficiency syndromes (1999) Abstract HIV M184I;M184V 135;135 142;142 34919029 Revealing the drug resistance mechanism of saquinavir due to G48V and V82F mutations in subtype CRF01_AE HIV-1 protease: molecular dynamics simulation and binding free energy calculations. In this work, the resistance mechanism against SQV due to active site mutations G48V and V82F in CRF01_AE (AE) protease was explored. 2021 Journal of biomolecular structure & dynamics Abstract HIV G48V;V82F 80;89 84;93 PR 111 119 34919029 Revealing the drug resistance mechanism of saquinavir due to G48V and V82F mutations in subtype CRF01_AE HIV-1 protease: molecular dynamics simulation and binding free energy calculations. The V82F mutant structure also maintains similar intramolecular hydrogen bond interactions as observed in AE-WT.Communicated by Ramaswamy H. 2021 Journal of biomolecular structure & dynamics Abstract HIV V82F 4 8 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. Interestingly, the combined PR-mutant HIV-1 (S534P/T536A or S534P/T536A/T538A) recovered its infectivity and reverted to S534, but maintained the T536A or T538A mutation, suggesting that HIV-1 replication in CD4+ T-cells can tolerate T536A and T538A Env mutations, but not S534P. 2021 Microbiology spectrum Abstract HIV S534P;T536A;T538A;S534P;S534P;T536A;T536A;T536A;T538A;T538A 60;66;72;45;273;51;146;234;155;244 65;71;77;50;278;56;151;239;160;249 Env;PR 250;28 253;30 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. Mutations of three highly conserved residues (S534P, T536A, or T538A) in the PR of HIV-1NL4-3 significantly decrease or eliminate viral infectivity due to defective fusion and increased gp120 shedding. 2021 Microbiology spectrum Abstract HIV S534P;T536A;T538A 46;53;63 51;58;68 gp120;PR 186;77 191;79 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. Sequencing of the env cDNA from cells infected with the recovered HIV-1 revealed that the S534P mutant reverted to serine or threonine at residue 534. 2021 Microbiology spectrum Abstract HIV S534P 90 95 Env 18 21 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. We found that HIV-1 Env containing serine to proline mutation at position 534 (S534P) are incapable of supporting virus-cell and cell-cell fusion. 2021 Microbiology spectrum Abstract HIV S534P;S534P 79;35 84;77 Env 20 23 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. MSM had higher odds of PDR to efavirenz/nevirapine (aOR: 2.0, 95% CI: 1.0-3.7, p = 0.04), reflecting ongoing transmission of mutations such as K103NS and E138A. 2021 Pathogens (Basel, Switzerland) Abstract HIV E138A;K103N;K103S 154;143;143 159;149;149 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. HIV-1 subtype B L74I and L74I/G140R mutants and HIV-1 subtype A6 I74L and I74/G140R mutants remained susceptible to cabotegravir; L74I/Q148R double mutants exhibited reduced susceptibility in HIV-1 subtypes B and A6 (half maximal effective capacity fold change, 4.4 and 4.1, respectively). 2022 Antimicrobial agents and chemotherapy Abstract HIV G140R;G140R;L74I;L74I;L74I;Q148R 78;30;16;25;130;135 83;35;20;29;134;140 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In cabotegravir breakthrough experiments, time to breakthrough was similar between L74 and I74 viruses across HIV-1 subtypes B and A6; Q148R was selected at low cabotegravir concentrations. 2022 Antimicrobial agents and chemotherapy Abstract HIV Q148R 135 140 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Reduced rilpivirine susceptibility was observed across HIV-1 subtypes B and A1 with resistance-associated mutations K101E or E138K (half maximal effective capacity fold change, 2.21 to 3.09). 2022 Antimicrobial agents and chemotherapy Abstract HIV E138K;K101E 125;116 130;121 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Retrospectively, the impact of L74I on in vitro sensitivity and durability of response to cabotegravir in HIV-1 subtype B and A6 backgrounds was studied. 2022 Antimicrobial agents and chemotherapy Abstract HIV L74I 31 35 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Site-directed L74I and mutations observed in participants with CVF were generated in HIV-1 subtype B and a consensus integrase derived from 3 subtype A6 CVF baseline sequences. 2022 Antimicrobial agents and chemotherapy Abstract HIV L74I 14 18 IN 117 126 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Therefore, the L74I integrase polymorphism did not differentially impact in vitro sensitivity to cabotegravir across HIV-1 subtype B and A6 integrase genes (ClinicalTrials.gov identifier: NCT02938520). 2022 Antimicrobial agents and chemotherapy Abstract HIV L74I 15 19 IN;IN 20;140 29;149 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Three participants who received long-acting therapy had confirmed virologic failure (CVF) at Week 48, and all had HIV-1 that was originally classified as subtype A1 and contained the baseline integrase polymorphism L74I; updated classification algorithms reclassified all 3 as HIV-1 subtype A6. 2022 Antimicrobial agents and chemotherapy Abstract HIV L74I 215 219 IN 192 201 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. Six (5.9%) participants experienced virologic failure, two of whom had RPV-associated mutations (K101E and Y181C) and a lamivudine-associated mutation (M184V/I). 2022 Journal of the International AIDS Society Abstract HIV K101E;M184I;M184V;Y181C 97;152;152;107 103;159;159;112 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. In contrast, a V260I mutation and its silent counterpart with a lower effect on ESS2b did not exhibit any differences in the splicing pattern. 2021 International journal of molecular sciences Abstract HIV V260I 15 20 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Results show that the previously described R263K drug-resistance-associated integrase mutation has additionally a severe effect on the ESE2b splicing regulatory element (SRE) in exon 2b, which causes loss of SD2b recognition. 2021 International journal of molecular sciences Abstract HIV R263K 43 48 IN 76 85 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. This was confirmed by an R263R silent mutation with a similar predicted effect on the exon 2b SRE. 2021 International journal of molecular sciences Abstract HIV R263R 25 30 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. This research focused on isolating the potential specific DNA aptamers against K103N/Y181C double mutant HIV-1 RT. 2022 Molecules (Basel, Switzerland) Abstract HIV K103N;Y181C 79;85 84;90 RT 111 113 35019252 [Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1)]. In the CPP-region, there were detected mutations (R53K, Q54H, Q54P, R57G) which were more common in sub-subtype A6 than in subtype B. 2022 Voprosy virusologii Abstract HIV Q54H;Q54P;R53K;R57G 56;62;50;68 60;66;54;72 35019252 [Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1)]. RESULTS AND DISCUSSION: Q54H and Q60H were identified as characteristic substitutions. 2022 Voprosy virusologii Abstract HIV Q54H;Q60H 24;33 28;37 35023287 Comparing effectiveness of first-line antiretroviral therapy between peri-urban and rural clinics in KwaZulu-Natal, South Africa. K103N (59%) and M184V (52%) were the most common mutations, followed by V106M and K65R (31% each). 2022 HIV medicine Abstract HIV K65R;M184V;V106M;K103N 82;16;72;0 86;21;77;5 35028668 Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study. Emergence of Q67H occurred at exposures below the dose used in current Phase 2/3 studies. 2022 The Journal of antimicrobial chemotherapy Abstract HIV Q67H 13 17 35028668 Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study. Post-monotherapy analyses revealed the emergence of CA mutation Q67H at Day 10 in two participants. 2022 The Journal of antimicrobial chemotherapy Abstract HIV Q67H 64 68 Capsid 52 54 35040990 Real-life experience with bictegravir/emtricitabine/tenofovir alafenamide in a large reference clinical centre. In PLWH carrying an M184V/I substitution, OT RNA <50 copies/mL was 89.5% at M6. 2022 The Journal of antimicrobial chemotherapy Abstract HIV M184I;M184V 20;20 27;27 35045265 Antiviral Activity and Resistance Profile of the Novel HIV-1 Non-Catalytic Site Integrase Inhibitor JTP-0157602. Resistance selection experiments of JTP-0157602 led to the emergence of A128T and T174I mutations, which are located at the lens epithelium-derived growth factor/p75 binding pocket of IN. 2022 Journal of virology Abstract HIV A128T;T174I 72;82 77;87 IN 184 186 35061384 Development of Novel Dihydrofuro[3,4-d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C. Especially, for the changeling mutations F227L/V106A and K103N/Y181C, both compounds exhibited remarkably improved activity compared to those of etravirine and rilpivirine. 2022 Journal of medicinal chemistry Abstract HIV F227L;K103N;V106A;Y181C 41;57;47;63 46;62;52;68 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. Additionally, the K103N/S mutation was mainly observed in clustered sequences (6.2% vs 2.8%). 2022 PloS one Abstract HIV K103N;K103S 18;18 25;25 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. Addition of E138K to G140S/Q148H conferred 35.5, 11.6 and 208-fold reduced susceptibility to dolutegravir, bictegravir, and cabotegravir, while addition of T97A to G140S/Q148H conferred 318, 121 and >1000-fold reduced susceptibility to these drugs. 2022 The Journal of antimicrobial chemotherapy Abstract HIV E138K;G140S;G140S;Q148H;Q148H;T97A 12;21;164;27;170;156 17;26;169;32;175;160 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. BACKGROUND: Routine HIV drug resistance genotyping identified an integrase sequence harbouring T97A, E138K, G140S and Q148H, with high predicted resistance to all integrase strand transfer inhibitors (INSTIs). 2022 The Journal of antimicrobial chemotherapy Abstract HIV E138K;G140S;Q148H;T97A 101;108;118;95 106;113;123;99 IN;IN;INSTI 65;163;201 74;172;207 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. Notably, bictegravir EC50 was significantly lower when T97A/E138K/G140S/Q148H was introduced into NL4.3, suggesting that other mutations in the autologous sequence enhanced resistance. 2022 The Journal of antimicrobial chemotherapy Abstract HIV E138K;G140S;Q148H;T97A 60;66;72;55 65;71;77;59 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. RESULTS: Q148H-containing viruses lacking G140S failed to propagate or mutated in vitro, consistent with fitness costs. 2022 The Journal of antimicrobial chemotherapy Abstract HIV G140S;Q148H 42;9 47;14 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. T97A and E138K further enhance the resistance conferred by G140S/Q148H, yielding >300-fold decreased susceptibility to all INSTIs when all four mutations are present. 2022 The Journal of antimicrobial chemotherapy Abstract HIV E138K;G140S;Q148H;T97A 9;59;65;0 14;64;70;4 INSTI 123 129 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. T97A or G140S alone conferred 3.6- to 5.6-fold decreased susceptibility to raltegravir and elvitegravir. 2022 The Journal of antimicrobial chemotherapy Abstract HIV G140S;T97A 8;0 13;4 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. T97A/E138K/G140S/Q148H in the autologous backbone conferred >300-fold reduced susceptibility to all INSTIs. 2022 The Journal of antimicrobial chemotherapy Abstract HIV E138K;G140S;Q148H;T97A 5;11;17;0 10;16;22;4 INSTI 100 106 35061879 Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. Two-mutation combinations conferred low-to-moderate resistance to raltegravir and elvitegravir only, except G140S/Q148H which eliminated raltegravir and elvitegravir activity and conferred 24.6-, 7.9-, and 107.5-fold reduced susceptibility to dolutegravir, bictegravir and cabotegravir. 2022 The Journal of antimicrobial chemotherapy Abstract HIV G140S;Q148H 108;114 113;119 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Molecular network analysis revealed three CRF07_BC clusters with TDR [two with Q58E (29/29) and one with K103N (10/19)]; and five CRF01_AE clusters with TDR [two with M46L (6/6), one with A98G (4/4), one with E138A (3/3), and one with K103R/V179D (3/3)]. 2021 Frontiers in microbiology Abstract HIV A98G;E138A;K103N;K103R;M46L;Q58E;V179D 188;209;105;235;167;79;241 192;214;110;240;171;83;246 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. TDR mutations detected in more than 10 cases were Q58E (n = 51), M46ILV (n = 46), K103N (n = 26), E138AGKQ (n = 25), K103R/V179D (n = 20), and A98G (n = 12). 2021 Frontiers in microbiology Abstract HIV A98G;E138A;E138G;E138K;E138Q;K103N;K103R;M46I;M46L;M46V;Q58E;V179D 143;98;98;98;98;82;117;65;65;65;50;123 147;106;106;106;106;87;122;71;71;71;54;128 35077642 Magnetic Bead Processing Enables Sensitive Ligation-Based Detection of HIV Drug Resistance Mutations. In studies with synthesized nucleic acids based on the well-studied HIV mutation, K103N, the assay successfully differentiated between wild-type and mutant for RNA targets with high specificity. 2022 Analytical chemistry Abstract HIV K103N 82 87 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Eighteen Gag mutations showed a significantly higher prevalence in PI/r-treated isolates compared to ART-naive (p < 0.05): Group 1 (prevalence < 1% in drug-naive): L449F, D480N, L483Q, Y484P, T487V; group 2 (prevalence 1-5% in drug-naive): S462L, I479G, I479K, D480E; group 3 (prevalence >= 5% in drug-naive): P453L, E460A, R464G, S465F, V467E, Q474P, I479R, E482G, T487A. 2022 Scientific reports Abstract HIV D480E;D480N;E460A;E482G;I479G;I479K;I479R;L449F;L483Q;P453L;Q474P;R464G;S462L;S465F;T487A;T487V;V467E;Y484P 261;171;317;359;247;254;352;164;178;310;345;324;240;331;366;192;338;185 266;176;322;364;252;259;357;169;183;315;350;329;245;336;371;197;343;190 Gag;PI 9;67 12;69 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Five Gag mutations (L449F, P453L, D480E, S465F, Y484P) positively correlated (Phi >= 0.2, p < 0.05) with protease-resistance mutations. 2022 Scientific reports Abstract HIV D480E;L449F;P453L;S465F;Y484P 34;20;27;41;48 39;25;32;46;53 PR;Gag 105;5 113;8 35089310 Co-evolution of drug resistance and broadened substrate recognition in HIV protease variants isolated from an Escherichia coli genetic selection system. One highly frequent side chain substitution, E34V, not regarded as a major drug resistance substitution was found in variants obtained under both selective conditions and is suggested to improve protease processing of the synthetic substrate. 2022 The Biochemical journal Abstract HIV E34V 45 49 PR 195 203 35092830 Prevalence of transmitted drug resistance among ART-naive HIV-infected individuals, Beijing, 2015-2018. K103N/KN (NNRTI associated) and M46L/I/IMV/IM/ML (protease inhibitor associated) were the other major resistance mutations. 2022 Journal of global antimicrobial resistance Abstract HIV K103K;K103N;M46I;M46L;M46M;M46V 0;0;32;32;32;32 7;7;48;48;48;48 PR;NNRTI 50;10 58;15 35092830 Prevalence of transmitted drug resistance among ART-naive HIV-infected individuals, Beijing, 2015-2018. The thymidine analogue mutations (TAMs) M41L/LM (4, 0.12%) and non-TAMs mutations M184V/MV/MI (8; 0.24%) were the primary NRTI-associated resistance mutations. 2022 Journal of global antimicrobial resistance Abstract HIV M184I;M184M;M184V;M41L;M41M 82;82;82;38;38 93;93;93;46;46 NRTI 122 126 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. Common mutations in RT were M184V (75%), T215Y (41.1%), K103N (39.3%), M41L (32.1%), D67DN (30.3%), G190A (28.6%) and A98G (26.8%). 2022 The Journal of antimicrobial chemotherapy Abstract HIV A98G;D67D;D67N;G190A;K103N;M184V;M41L;T215Y 118;85;85;100;56;28;71;41 122;90;90;105;61;33;75;46 RT 20 22 35134180 Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations In HIV-2 Integrase: A Phenotypic Analysis Using An Expanded Panel of Site-Directed Mutants. HIV-2-specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterized, significantly increased the EC50 for raltegravir when introduced into one or more mutational backgrounds; mutations E92A/Q, T97A, and G140A/S conferred similar enhancements of dolutegravir resistance. 2022 The Journal of infectious diseases Abstract HIV A153G;E92A;E92A;E92Q;G140A;G140S;H157Q;H157S;Q91R;T97A 47;41;229;229;247;247;58;58;35;237 52;45;235;235;254;254;65;65;39;241 IN 15 24 35134180 Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations In HIV-2 Integrase: A Phenotypic Analysis Using An Expanded Panel of Site-Directed Mutants. HIV-2ROD9 variants encoding G118R alone, or insertions of residues SREGK or SREGR at position 231, were resistant to both INIs. 2022 The Journal of infectious diseases Abstract HIV G118R 28 33 IN 122 126 35134966 Prevalence of doravirine cross-resistance in HIV-infected adults who failed first-line ART in China, 2014-18. High-level resistance was mainly due to Y188L (3.2%) and M230L (2.7%). 2022 The Journal of antimicrobial chemotherapy Abstract HIV M230L;Y188L 57;40 62;45 35134966 Prevalence of doravirine cross-resistance in HIV-infected adults who failed first-line ART in China, 2014-18. The most frequent doravirine-associated resistance mutations were V106M (8.7%), K101E (6.8%) and P225H (5.1%). 2022 The Journal of antimicrobial chemotherapy Abstract HIV K101E;P225H;V106M 80;97;66 85;102;71 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. General consensus suggests that even singleton E138A mutations in HIV reverse transcriptase at baseline are associated with resistance to rilpivirine (RPV). 2022 Clinical case reports Abstract HIV E138A 47 52 RT 70 91 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. We detected 11 pre-existing E138A carriers treated with RPV in the pan European EuResist database. 2022 Clinical case reports Abstract HIV E138A 28 33 35157024 HIV-1 drug resistance profiling using amino acid sequence space cartography. V32I, L10F, and L33F in HIV protease) for the resistance development. 2022 Bioinformatics (Oxford, England) Abstract HIV L10F;L33F;V32I 6;16;0 10;20;4 PR 28 36 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. A discordant protease inhibitor mutation/wild-type T74PT in plasma but not in cerebrospinal fluid indicated poor central nervous system penetration due to the selective pressure of drug therapy. 2022 Journal of medical case reports Abstract HIV T74P;T74T 51;51 56;56 PR 13 21 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. In this study, we investigate how T18A TCR, which is beneficial for a long-term control of HIV in clinic, recognizes immunodominant Gag epitope TL9 (TPQDLTML180-188) from HIV in the context of the antigen presenting molecule HLA-B*81:01. 2022 Frontiers in immunology Abstract HIV T18A 34 38 Gag 132 135 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Remarkably, the CDR3beta in T18A complexes does not contact with TL9 at all but with intensive contacts to HLA-B*81:01. 2022 Frontiers in immunology Abstract HIV T18A 28 32 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The binding kinetic data of T18A TCR revealed that this TCR can recognize TL9 epitope and several mutant versions, which might explain the correlation of T18A TCR with better clinic outcomes despite the relative high mutation rate of HIV. 2022 Frontiers in immunology Abstract HIV T18A;T18A 28;154 32;158 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. We found that T18A TCR exhibits differential recognition for TL9 restricted by HLA-B*81:01. 2022 Frontiers in immunology Abstract HIV T18A 14 18 35190973 Main lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in HIV-1 subtypes C and B. HIV-1C Tat substitution (C30S) did not interfere with the CNS migration of the main lymphocyte subpopulations. 2022 Journal of neurovirology Abstract HIV C30S 25 29 Tat 7 10 35192922 Acquired HIV drug resistance mutations on first-line antiretroviral therapy in Southern Africa: Systematic review and Bayesian evidence synthesis. Patients failing first-line ART including emtricitabine or lamivudine showed high levels of the M184V/I mutation after two years: 75.7% (95% Credibility Interval [CrI] 61.9%-88.9%) if combined with tenofovir, and 72.1% (95% CrI 56.8%-85.9%) with zidovudine. 2022 Journal of clinical epidemiology Abstract HIV M184I;M184V 96;96 103;103 35192922 Acquired HIV drug resistance mutations on first-line antiretroviral therapy in Southern Africa: Systematic review and Bayesian evidence synthesis. With tenofovir disoproxil fumarate, the prevalence of the K65R mutation was 52.0% (95% CrI 32.5%-76.8%) at two years. 2022 Journal of clinical epidemiology Abstract HIV K65R 58 62 35207677 Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort. We excluded patients with HBsAg positivity, evidence of non-nucleoside reverse transcriptase inhibitor (except K103N) and integrase inhibitor mutations, and with a detectable HIV-RNA (>50 copies/mL). 2022 Journal of personalized medicine Abstract HIV K103N 111 116 NNRTI;IN 56;122 92;131 35212226 Hybrid QM/MM Free-Energy Evaluation of Drug-Resistant Mutational Effect on the Binding of an Inhibitor Indinavir to HIV-1 Protease. Here, we present a molecular simulation study on the ligand binding of indinavir, a potent transition state analogue inhibitor, to the wild-type protein and a V82T/I84V drug-resistant mutant of the HIV-1 protease. 2022 Journal of chemical information and modeling Abstract HIV I84V;V82T 164;159 168;163 PR 204 212 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. M184I was the most prevalent clinically important variant, seen in 37% of participants. 2022 Viruses Abstract HIV M184I 0 5 35217069 Novel RNase H Inhibitors Blocking RNA-directed Strand Displacement DNA Synthesis by HIV-1 Reverse Transcriptase. D443N or E478Q) has no significant effect on strand displacement while copying DNA templates, but has a large impact on DNA polymerization in reactions carried out with RNA templates. 2022 Journal of molecular biology Abstract HIV E478Q;D443N 9;0 14;5 35229630 High Rate of HIV-1 Drug Resistance in Antiretroviral Therapy-Failure Patients in Liaoning Province, China. G190S (31.25%) and Y181C (25.78%) mutations were the most common NNRTIs resistance mutations. 2022 AIDS research and human retroviruses Abstract HIV Y181C;G190S 19;0 24;5 NNRTI 65 71 35229630 High Rate of HIV-1 Drug Resistance in Antiretroviral Therapy-Failure Patients in Liaoning Province, China. K65R (29.69%), M184V (28.52%) were the most common NRTIs resistance mutations. 2022 AIDS research and human retroviruses Abstract HIV M184V;K65R 15;0 20;4 NRTI 51 56 35240975 Integrase Strand Transfer Inhibitor (INSTI) Genotypic Resistance Analysis in Treatment-nNaive, INSTI Free Antiretroviral-Experienced and INSTI-Experienced Turkish Patients Infected with HIV-1. Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients. 2022 Current HIV research Abstract HIV E138K;E138K;E138T;E157Q;E192Q;E92Q;G140A;G140A;G140S;N155H;Q148H;Q148R;Q148R;S147G;S147G 28;94;94;135;87;22;35;103;103;128;119;53;119;42;112 33;101;101;140;92;26;40;110;110;133;126;58;126;47;117 35240975 Integrase Strand Transfer Inhibitor (INSTI) Genotypic Resistance Analysis in Treatment-nNaive, INSTI Free Antiretroviral-Experienced and INSTI-Experienced Turkish Patients Infected with HIV-1. Major INSTI-mutations E138K, Y143R, S147G, Q148R, N155H, and E157Q were found in raltegravir. 2022 Current HIV research Abstract HIV E138K;E157Q;N155H;Q148R;S147G;Y143R 22;61;50;43;36;29 27;66;55;48;41;34 INSTI 6 11 35274144 Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression. PBMC DNA deep sequencing performed some months later revealed mutations M184I (14.29%) and M230I (6.25%) in the reverse transcriptase and G163R (9.77%) and S230N (98.8%) in the integrase. 2022 The Journal of antimicrobial chemotherapy Abstract HIV G163R;M184I;M230I;S230N 138;72;91;156 143;77;96;161 RT;IN 112;177 133;186 35274144 Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression. Plasma HIV-1 genotypic deep sequencing (Vela System) revealed the emergence of R263K (79.6%) and S230N (99.4%) mutations in the integrase region (intermediate resistance to dolutegravir, score = 30 Stanford HIVDB 9.0). 2022 The Journal of antimicrobial chemotherapy Abstract HIV R263K;S230N 79;97 84;102 IN 128 137 35274144 Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression. R263K was only found at extremely low levels (0.07%). 2022 The Journal of antimicrobial chemotherapy Abstract HIV R263K 0 5 35274144 Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression. We aim to report, to the best of our knowledge, the first case of selection of the key integrase mutation R263K in a subject treated with this regimen started as a switch strategy with undetectable plasma HIV-1 viraemia. 2022 The Journal of antimicrobial chemotherapy Abstract HIV R263K 106 111 IN 87 96 35277871 Analysis of HIV-1 integrase genotypes and polymorphisms among integrase inhibitors-based antiretroviral treatment naive patients in South Sudan. Major INSTI resistance mutations were absent, however, polymorphic accessory mutations at positions M50ILR (26.6%) and L74I (3.3%) were detected. 2022 Journal of medical virology Abstract HIV L74I;M50I;M50L;M50R 119;100;100;100 123;106;106;106 INSTI 6 11 35290812 Viral resistance to VRC01-like antibodies with mutations in loop D and V5 from an HIV-1 B' subtype infected individual with broadly neutralization activity. For DRVI01-derived viruses, the single N464T change fully produced VRC01-resistant variants; conversely, a single T464N mutation generated VRC01-susceptible variants. 2022 Molecular immunology Abstract HIV N464T;T464N 39;114 44;119 35290812 Viral resistance to VRC01-like antibodies with mutations in loop D and V5 from an HIV-1 B' subtype infected individual with broadly neutralization activity. Site-directed mutagenesis revealed that E279D/R282K/N460A/T464N of gp120 from DRVI01 produced VRC01-susceptible variants. 2022 Molecular immunology Abstract HIV E279D;N460A;R282K;T464N 40;52;46;58 45;57;51;63 gp120 67 72 35293098 Pretreatment drug resistance in people living with HIV: A large retrospective cohort study in Chongqing, China. The predominant DRMs for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were V179D/E/A/DIN (13.60%) and M184V/I (1.44%), respectively, whereas only two major DRMs (M46L and I54L) were identified for protease inhibitors (PIs). 2022 HIV medicine Abstract HIV I54L;M184I;M184V;M46L;V179A;V179D;V179E;V179I;V179N 239;170;170;230;143;143;143;143;143 243;177;177;235;156;156;156;156;156 NNRTI;NRTI;PR;NNRTI;NRTI;PI 25;86;265;74;131;286 61;118;273;80;136;289 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Since this genotype also negatively impacted the development of central nervous system (CNS) lesions in animals infected with the parental source of CL757, we sought to generate a TRIM5alphaTFP/TFP-resistant clone, SIV-804E-CL757-P37S/R98S (CL757-SS), using a similar strategy. 2022 Microbiology spectrum Abstract HIV P37S;R98S 230;235 234;239 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. This P146T substitution in a conserved disordered linker region in the C-terminal domain of capsid (CA-CTD) has been shown to inhibit proper formation of HIV-1 capsid particles. 2022 Microbiology spectrum Abstract HIV P146T 5 10 Capsid;Capsid;Capsid 92;160;100 98;166;102 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. We have previously shown that polymorphisms in the TRIM5alpha B30.2/SPRY domain impact the level of SIVsmm viremia in RM and that amino acid substitutions (P37S/R98S) in the capsid N-terminal domain (CA-NTD) enables the virus to overcome restriction in RMs with the restrictive homozygous TRIM5alphaTFP/TFP genotype. 2022 Microbiology spectrum Abstract HIV P37S;R98S 156;161 160;165 Capsid;Capsid 174;200 180;202 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. We utilized a previous deep mutational scan of HIV-1 protease (PR) to identify variants with 15-45 per cent defects in replication and analysed the biochemical function of eight variants (L10M, L10S, V32C, V32I, A71V, A71S, Q92I, Q92N). 2021 Virus evolution Abstract HIV A71S;A71V;L10M;L10S;Q92I;Q92N;V32C;V32I 218;212;188;194;224;230;200;206 222;216;192;198;228;234;204;210 PR;PR 53;63 61;65 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. Furthermore, one patient having S230R mutation resulted in low-level resistance to RAL, EVG, DTG and BIC. 2022 Pharmacogenomics and personalized medicine Abstract HIV S230R 32 37 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. Two patients have E138A and G163R mutations respectively and both could cause low-level resistance to RAL and EVG. 2022 Pharmacogenomics and personalized medicine Abstract HIV E138A;G163R 18;28 23;33 35301540 Characterization of Human Immunodeficiency Virus (HIV) Infections in Women Who Received Injectable Cabotegravir or Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Prevention: HPTN 084. Nine women in the TDF/FTC arm had nonnucleoside reverse-transcriptase inhibitor resistance; 1 had the nucleoside reverse-transcriptase inhibitor resistance mutation, M184V. 2022 The Journal of infectious diseases Abstract HIV M184V 166 171 NNRTI;NRTI 34;102 69;134 35302390 Molecular characterisation of the pol gene of vertically transmitted HIV-1 strains in children with virological failure. At BL, K103N (5), E138A/G (4) and M184V (3) were the most common mutations. 2022 AIDS research and human retroviruses Abstract HIV E138A;E138G;K103N;M184V 18;18;7;34 25;25;12;39 35302390 Molecular characterisation of the pol gene of vertically transmitted HIV-1 strains in children with virological failure. M184V/I, K103N/S and Y181C were the most commonly occurring mutations, seen in 76%, 51% and 36% children. 2022 AIDS research and human retroviruses Abstract HIV K103N;K103S;M184I;Y181C;M184V 9;9;0;21;0 16;16;7;26;7 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Quantitative PCR and in situ immunofluorescence assays confirm this bias of the K258R mutant virus for integration into centromeric DNA. 2022 Nature communications Abstract HIV K258R 80 85 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R point mutation in HIV-1 IN is also present in databases of latent proviruses found in patients, and may reflect an unappreciated aspect of the establishment of viral latency. 2022 Nature communications Abstract HIV K258R 4 9 IN 34 36 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Viruses carrying the K258R IN mutation exhibit a high frequency of integrations into centromeric alpha satellite repeat sequences, as assessed by deep sequencing, a more than 10-fold increase over wild-type. 2022 Nature communications Abstract HIV K258R 21 26 IN 27 29 35336931 DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks). DT started within 7 days of first specialist consultation in all patients and the same day in 84.1%; 3.4% had baseline resistance mutations (K103N, V106I + E138A, and V108I); 12.5% were lost to follow-up. 2022 Viruses Abstract HIV E138A;K103N;V106I;V108I 156;141;148;167 161;146;153;172 35343783 Functional and Highly Cross-Linkable HIV-1 Envelope Glycoproteins Enriched in a Pretriggered Conformation. Two common polymorphisms, Q114E and Q567K, as well as a known variant, A582T, additively rendered pseudoviruses resistant to cold, soluble CD4, and a CD4-mimetic compound, phenotypes indicative of stabilization of the pretriggered state-1 Env conformation. 2022 Journal of virology Abstract HIV A582T;Q114E;Q567K 71;26;36 76;31;41 Env 239 242 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Loss of Env-EL9 responses was concomitant with selecting K588R + L592R mutations at Env-EL9. 2022 Retrovirology Abstract HIV K588R;L592R 57;65 62;70 Env;Env 8;84 11;87 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. The K588R + L592R escape variant was directly related to HIV-1 increase replicative capacity and stability of Env at the LVC. 2022 Retrovirology Abstract HIV K588R;L592R 4;12 9;17 Env 110 113 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. We analysed viral evolution and immune escape in HLA-B*14:02 restricted CD8 + T -cell epitopes and identified viral evolution at the Env-EL9 epitope selecting the L592R mutation. 2022 Retrovirology Abstract HIV L592R 163 168 Env 133 136 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. GI11 (Gag) was conserved and strong GI11 (Gag)-specific T-cell responses showed cross-reactivity with a dominant variant, M228I, found in 3/12 patients; GI11 (Gag)-specific T-cell responses were positively associated with CD4 T-cell counts (R = 0.716, P = 0.046). 2022 BMC immunology Abstract HIV M228I 122 127 Gag;Gag;Gag 6;42;159 9;45;162 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Interestingly, the GI9 (Pol) epitope was also conserved, but GI9 (Pol)-specific T-cell responses did not influence disease progression (P > 0.05), while a D490G variant identified in one patient did not affect CD4 T-cell counts. 2022 BMC immunology Abstract HIV D490G 155 160 Pol;Pol 24;66 27;69 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs. 2022 Frontiers in cellular and infection microbiology Abstract HIV F277W;S465T 37;91 42;96 gp41 46 50 35393931 HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. 2022 Euro surveillance Abstract HIV E138A;K65R;M184V;V108I 148;70;58;138 153;74;65;143 35394614 HIV-1 subtype C Tat exon-1 amino acid residue 24K is a signature for neurocognitive impairment. The results support a linkage between HIV-1 C Tat N24K polymorphism, proviral load, immunosuppression, and neurocognitive impairment. 2022 Journal of neurovirology Abstract HIV N24K 50 54 Tat 46 49 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. A 100 ns molecular dynamics (MD) simulation and MM-PBSA calculations were performed to study the molecular mechanism of M46I-mutation-based saquinavir resistance. 2022 Viruses Abstract HIV M46I 120 124 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. In conclusion, the M46I mutation induced structural dynamics changes that weaken the protease grip on saquinavir without distorting the active site of the protein. 2022 Viruses Abstract HIV M46I 19 23 PR 85 93 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. M46I, a non-active site mutation in HIV-1 protease has been clinically associated with saquinavir resistance in HIV patients. 2022 Viruses Abstract HIV M46I 0 4 PR 42 50 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The M46I mutation significantly affects the energetics and conformational stability of HIV-1 protease in terms of RMSD, RMSF, Rg, SASA, and hydrogen formation potential. 2022 Viruses Abstract HIV M46I 4 8 PR 93 101 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The predominant open conformation was reduced, but inward flap curling/active site compactness was increased in the presence of saquinavir in M46I HIV-1 protease. 2022 Viruses Abstract HIV M46I 142 146 PR 153 161 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. This mutation significantly decreased van der Waals interaction and binding free energy ( G) in the M46I-saquinavir complex and induced inward flap curling and a wider opening of the flaps for most of the MD simulation period. 2022 Viruses Abstract HIV M46I 100 104 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Analysis of the genetic barrier showed that the Q148H/K/R dolutegravir resistance pathway was less selected in subtype C. 2022 Viruses Abstract HIV Q148H;Q148K;Q148R 48;48;48 57;57;57 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. However, we found E92G in one ART-naive patient specimen and accessory mutations in 20/460 (4.3%) of the specimens. 2022 Viruses Abstract HIV E92G 18 22 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. From the Tat signatures linked to neuropathogenesis, only R57/R57S are involved in Tat-TAR interaction. 2022 Frontiers in microbiology Abstract HIV R57S 62 66 Tat;Tat 9;83 12;86 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. In this study, we attempted to understand the molecular mechanism by which Tat subtype-specific variation, particularly, C31S, R57S, and Q63E influence the Tat-TAR interaction. 2022 Frontiers in microbiology Abstract HIV C31S;Q63E;R57S 121;137;127 125;141;131 Tat;Tat 75;156 78;159 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Subtype-specific Tat protein signatures including C31S, R57S and Q63E present in Tat subtype C has previously been linked to a lowered neuropathophysiology compared to Tat subtype B. 2022 Frontiers in microbiology Abstract HIV C31S;Q63E;R57S 50;65;56 54;69;60 Tat;Tat;Tat 17;81;168 20;84;171 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. Among adult participants, factors associated with preexisting M184 V/I included other resistance, Black race, Hispanic/Latinx ethnicity, lower baseline CD4 cell count, advanced HIV disease, longer duration of antiretroviral therapy, and greater number of prior third agents. 2022 AIDS (London, England) Abstract HIV M184I;M184V 62;62 70;70 HIV diseases 177 188 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. At last on-treatment visit, 98% (179/182) with preexisting M184 V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA <50 copies/mL, with no treatment-emergent resistance to B/F/TAF. 2022 AIDS (London, England) Abstract HIV M184I;M184V 59;59 67;67 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. CONCLUSIONS: M184 V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. 2022 AIDS (London, England) Abstract HIV M184I;M184V 13;13 21;21 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. Most substitutions were M184 V (n = 161) or M184 V/I mixtures (n = 10). 2022 AIDS (London, England) Abstract HIV M184I;M184V;M184V 44;44;24 52;52;30 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. OBJECTIVE: We investigated the prevalence of preexisting M184 V/I and associated risk factors among clinical trial participants with suppressed HIV and evaluated the impact of M184 V/I on virologic response after switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). 2022 AIDS (London, England) Abstract HIV M184I;M184I;M184V;M184V 57;176;57;176 65;184;65;184 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. Other resistance substitutions were often detected in addition to M184 V/I (n = 147). 2022 AIDS (London, England) Abstract HIV M184I;M184V 66;66 74;74 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. Preexisting M184 V/I was identified in 182 (10%), mostly by baseline proviral DNA genotype (n = 167). 2022 AIDS (London, England) Abstract HIV M184I;M184V 12;12 20;20 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. Stepwise selection identified potential risk factors for M184 V/I in a multivariate logistic regression model. 2022 AIDS (London, England) Abstract HIV M184I;M184V 57;57 65;65 35466963 High Efficacy of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in People with Suppressed HIV and Preexisting M184 V/I. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184 V/I. 2022 AIDS (London, England) Abstract HIV M184I;M184V 121;121 129;129 35481647 Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer. Based on this structural model of the monomer, p66L289K and p51 were predicted to form a heterodimer while p66 and p51L289K not. 2022 Protein science Abstract HIV L289K;P51K;P51L;P66K;P66L 50;115;115;47;47 55;123;123;55;55 35481647 Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer. Here, small-angle X-ray scattering (SAXS) with proton paramagnetic relaxation enhancement (PRE), 19 F site-specific NMR, and size exclusion chromatography (SEC) were performed for the p66 monomer with the L289K mutation, p66L289K . 2022 Protein science Abstract HIV L289K;L289K;P66K;P66L 224;205;221;221 229;210;229;229 35481647 Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer. Several single amino acid substitutions in RT, including L289K, decrease p66/p51 dimer affinity, and reduce enzymatic functioning. 2022 Protein science Abstract HIV L289K 57 62 RT 43 45 35481647 Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer. We tested this hypothesis by SEC analysis of p66 and p51 containing L289K in different combinations and clearly demonstrated that L289K substitution in the p51 subunit, but not in the p66 subunit, reduces p66/p51 formation. 2022 Protein science Abstract HIV L289K;L289K 68;130 73;135 35485330 Evaluation of doravirine-based regimen population target in a large Italian clinical center. The most common DOR-related RAM were V106A, Y181V, and Y188L. 2021 Antiviral therapy Abstract HIV V106A;Y181V;Y188L 37;44;55 42;49;60 35485330 Evaluation of doravirine-based regimen population target in a large Italian clinical center. We also analyzed RAM that can possibly interfere with combination therapy (mostly K65R and M184V). 2021 Antiviral therapy Abstract HIV K65R;M184V 82;91 86;96 35485331 Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)-infected patients. The most common DOR resistance mutations observed among the naive patients were A98G and K101E (0.2% each), and those among cART-experienced patients were L100I (2.0%), K101E, V108I, H221Y, and P225H (1.5% each). 2021 Antiviral therapy Abstract HIV A98G;H221Y;K101E;K101E;L100I;P225H;V108I 80;183;89;169;155;194;176 84;188;94;174;160;199;181 35491829 Doravirine and Islatravir Have Complementary Resistance Profiles and Create a Combination with a High Barrier to Resistance. Based on the frequent emergence of F227C, we hypothesized that DOR and ISL would create a combination (DOR/ISL) with a high barrier to resistance. 2022 Antimicrobial agents and chemotherapy Abstract HIV F227C 35 40 35491829 Doravirine and Islatravir Have Complementary Resistance Profiles and Create a Combination with a High Barrier to Resistance. Isolate hypersusceptibility to ISL required F227C, in contrast to zidovudine, an NRTI, which required M184V. 2022 Antimicrobial agents and chemotherapy Abstract HIV F227C;M184V 44;102 49;107 NRTI 81 85 35491829 Doravirine and Islatravir Have Complementary Resistance Profiles and Create a Combination with a High Barrier to Resistance. Six isolates bearing NRTI RAMs (M184V and/or K65R) were resistant to lamivudine (3TC) and emtricitabine (FTC) but not to other approved NRTIs. 2022 Antimicrobial agents and chemotherapy Abstract HIV K65R;M184V 45;32 49;38 NRTI;NRTI 21;136 25;141 35491829 Doravirine and Islatravir Have Complementary Resistance Profiles and Create a Combination with a High Barrier to Resistance. The most common DOR resistance-associated mutation (RAM) detected in 5 of the 7 resistant isolates was F227C. 2022 Antimicrobial agents and chemotherapy Abstract HIV F227C 103 108 35495657 Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters. The most prevalent TDR drug resistance mutations, in both LP and NLP, were K103N/S, T215rev, T215FY, M184I/V, M41I/L, M46I/L, and L90M. 2022 Frontiers in microbiology Abstract HIV K103N;K103S;L90M;M184I;M184V;M41I;M41L;M46I;M46L;T215F;T215Y 75;75;130;101;101;110;110;118;118;93;93 82;82;134;108;108;116;116;124;124;99;99 35502922 Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1. Predefined gp120 substitutions, most commonly M426L or S375N, were emergent on treatment in 24/50 (48%) RC and 33/44 (75%) NRC participants with PDVF, with related increases in temsavir IC50 FC. 2022 Antimicrobial agents and chemotherapy Abstract HIV M426L;S375N 46;55 51;60 gp120 11 16 35502922 Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1. The incidence of PDVF was as expected in this difficult-to-treat patient population and, among RC participants, was comparable regardless of the presence of predefined gp120 amino acid substitutions that potentially influence phenotypic susceptibility to temsavir (S375H/I/M/N/T, M426L, M434I, M475I) or baseline temsavir 50% inhibitory concentration fold change (IC50 FC). 2022 Antimicrobial agents and chemotherapy Abstract HIV M426L;M434I;M475I;S375H;S375I;S375M;S375N;S375T 280;287;294;265;265;265;265;265 285;292;299;278;278;278;278;278 gp120 168 173 35505490 Performance of the GenoType MTBDRsl in a programmatic setting, South Africa. The most common mutation observed in case of fluoroquinolone resistance occurred at the gyrA gene, codon 90 (A90V) (61/158, 38.6%), and the most common mutation in injectable aminoglycoside resistance occurred in the rrs region, A1401G (71/108, 65.7%).CONCLUSION: In HIV-TB-prevalent settings, routine use of the MTBDRsl is more effective when performed directly on smear-positive specimens. 2022 The international journal of tuberculosis and lung disease Abstract HIV A1401G;A90V 229;109 235;113 35509014 Impact of low-level viremia with drug resistance on CD4 cell counts among people living with HIV on antiretroviral treatment in China. Of 1818 patients with VL 50-999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/muL (AOR 3.8, 95% CI 2.6-5.5, p < 0.01) comparing with those without HIVDR. 2022 BMC infectious diseases Abstract HIV K103N;M184I;M184V;V181C;V181I;V181V 115;100;100;132;132;132 120;107;107;141;141;141 35509014 Impact of low-level viremia with drug resistance on CD4 cell counts among people living with HIV on antiretroviral treatment in China. Of 925 patients with VL >= 1000 copies/mL, 495 (53.5%) acquired HIVDR, the most common DRAM were K103N 43.8%, M184I/V 43.2%, M41L 19.0%, D67N/G 16.4%, V181C/I/V 14.5%, G190A/S 13.9% and K101E 13.7% (multidrug resistance: 75.8%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/muL (AOR 5.8, 95% CI 4.6-7.4, p < 0.01) comparing with those without HIVDR. 2022 BMC infectious diseases Abstract HIV D67G;D67N;G190A;G190S;K101E;K103N;M184I;M184V;M41L;V181C;V181I;V181V 137;137;168;168;186;97;110;110;125;151;151;151 143;143;175;175;191;102;117;117;129;160;160;160 35511892 Increased viral load in a hospitalized patient on treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide: A case report and review of the literature. At the time of regimen change (HD 67), a resistance panel showed minor mutations, E157Q and V118I. 2022 American journal of health-system pharmacy Abstract HIV E157Q;V118I 82;92 87;97 7474123 Mutagenic analysis of human immunodeficiency virus type 1 Vpr: role of a predicted N-terminal alpha-helical structure in Vpr nuclear localization and virion incorporation. Furthermore, a single mutation (E25K) located on the hydrophilic face of this predicted alpha-helical structure affected not only virion incorporation but also nuclear localization of Vpr. 1995 Journal of virology Abstract HIV E25K 32 36 Vpr 184 187 7474123 Mutagenic analysis of human immunodeficiency virus type 1 Vpr: role of a predicted N-terminal alpha-helical structure in Vpr nuclear localization and virion incorporation. Interestingly, our results show that two Vpr mutants harboring single amino acid substitutions (L to F at position 23 [L23F] and A30F) on the hydrophobic face of the predicted helix coded for relatively stable proteins that retained their ability to translocate to the nucleus but exhibited dramatic reduction in Vpr incorporation, suggesting that this hydrophobic face might mediate protein-protein interactions required for Vpr virion incorporation but not nuclear localization. 1995 Journal of virology Abstract HIV A30F;L23F 129;119 133;123 Vpr;Vpr;Vpr 41;313;426 44;316;429 7479728 Trans-dominant inhibitory human immunodeficiency virus type 1 protease monomers prevent protease activation and virion maturation. Coexpression of the wt proviral DNA (HIV-gpt) with increasing amounts of the mutant proviral DNA (HIV-gpt D25N) results in a concomitant decrease in proteolytic activity monitored by in vivo viral polyprotein processing. 1995 Proc Natl Acad Sci U S A Abstract HIV D25N 106 110 7479728 Trans-dominant inhibitory human immunodeficiency virus type 1 protease monomers prevent protease activation and virion maturation. The trans-dominant inhibitory activity of a defective protease monomer with the active site Asp-25 changed to Asn was measured by transient transfection. 1995 Proc Natl Acad Sci U S A Abstract HIV D25N 92 113 PR;Asp 54;92 62;95 7486942 K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. Cloned variants of human immunodeficiency virus type 1 that contain the K65R mutation in reverse transcriptase have previously been shown to display approximately 10- to 30-fold resistance against 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and 2',3'-dideoxy-3'-thiacytidine. 1995 Antimicrobial agents and chemotherapy Abstract HIV K65R 72 76 RT 89 110 7486942 K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. Likewise, a chain termination system revealed that mutated recombinant K65R reverse transcriptase displays resistance to PMEA diphosphate, the active metabolite of PMEA, in cell-free enzyme assays. 1995 Antimicrobial agents and chemotherapy Abstract HIV K65R 71 75 RT 76 97 7486942 K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. On the basis of tissue culture studies with both primary T cells and established cell lines, we now report that the K65R mutation confers approximately 12- to 15-fold resistance to 9-(2-phosphonylmethoxyethyl)adenine (PMEA). 1995 Antimicrobial agents and chemotherapy Abstract HIV K65R 116 120 7486942 K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. Parallel studies have shown that the M184V mutation in reverse transcriptase, associated with high-level resistance against the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine, does not confer resistance to PMEA in tissue culture. 1995 Antimicrobial agents and chemotherapy Abstract HIV M184V 37 42 RT 55 76 7486942 K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine. Viruses and enzymes that included both the K65R and M184V mutations were resistant to PMEA and PMEa diphosphate, respectively, but only to the extent conferred by the K65R mutation alone. 1995 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;M184V 43;167;52 47;171;57 7490732 Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepinones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcriptase enzymes. An evaluation, against Y181C RT, of previously described analogs of nevirapine revealed that the 2-chlorodipyridodiazepinone 16 is an effective inhibitor of this mutant enzyme. 1995 Journal of medicinal chemistry Abstract HIV Y181C 23 28 RT 29 31 7490732 Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepinones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcriptase enzymes. In addition, the substitution pattern at C-4, N-5, and N-11 of the dipyridodiazepinone ring system optimum for inhibition of both wild-type and Y181C RT is no longer the 4-methyl-11-cyclopropyl substitution preferred against the wild-type enzyme but rather the 5-methyl-11-ethyl (or 11-cyclopropyl) pattern. 1995 Journal of medicinal chemistry Abstract HIV Y181C 144 149 RT 150 152 7490732 Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepinones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcriptase enzymes. The detailed examination of the structure-activity relationship of 2-substituted dipyridodiazepinones presented below shows that combined activity against the wild-type and Y181C enzymes is achieved with aryl substituents at the 2-position of the tricyclic ring system. 1995 Journal of medicinal chemistry Abstract HIV Y181C 173 178 7490732 Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepinones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcriptase enzymes. The major cause of viral resistance to the potent human immunodeficiency virus type 1 reverse transcriptase (RT) inhibitor nevirapine is the mutation substituting cysteine for tyrosine-181 in RT (Y181C RT). 1995 Journal of medicinal chemistry Abstract HIV Y181C;Y181C 196;163 202;188 RT;RT;RT;RT 86;109;192;202 107;111;194;204 7490732 Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepinones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcriptase enzymes. The more potent 2-substituted dipyridodiazepinones were evaluated against mutant RT enzymes (L100I RT, K103N RT, P236L RT, and E138K RT) that confer resistance to other non-nucleoside RT inhibitors, and compounds 42, 62, and 67, with pyrrolyl, aminophenyl, and aminopyridyl substituents, respectively, at the 2-position, were found to be effective inhibitors of these mutant enzymes also. 1995 Journal of medicinal chemistry Abstract HIV E138K;K103N;L100I;P236L 127;103;93;113 132;108;99;118 RT;RT;RT;RT;RT;RT 81;99;109;119;133;184 83;101;111;121;135;186 7490733 Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 5. 4-Substituted and 2,4-disubstituted analogs of nevirapine. Attempts to combine these results with the recent discovery that 2-substituents enhance activity against the Y181C mutant led to a few compounds with moderate activity against both enzymes. 1995 Journal of medicinal chemistry Abstract HIV Y181C 109 114 7490733 Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 5. 4-Substituted and 2,4-disubstituted analogs of nevirapine. Furthermore certain derivatives appear to inhibit the Y181C mutant RT. 1995 Journal of medicinal chemistry Abstract HIV Y181C 54 59 RT 67 69 7492119 Analysis of mutations at position 184 in reverse transcriptase of human immunodeficiency virus type 1. The variants Met184Ile and Met184Val showed slight reductions in processivity relative to that of the wild-type enzyme; the variants Met184Ala and Met184Leu showed considerable reductions in their processivity. 1995 Antimicrobial agents and chemotherapy Abstract HIV M184A;M184I;M184L;M184V 133;13;147;27 142;22;156;36 7493942 Mutational analysis of the substrate binding pocket of murine leukemia virus protease and comparison with human immunodeficiency virus proteases. Mutations at the predicted S2/S2' subsites of MuLV PR have a strong influence on the substrate specificity of this enzyme, as observed with mutants H37D, V39I, V54I, A57I, and L92I. 1995 The Journal of biological chemistry Abstract HIV A57I;H37D;L92I;V39I;V54I 166;148;176;154;160 170;152;180;158;164 PR 51 53 7493942 Mutational analysis of the substrate binding pocket of murine leukemia virus protease and comparison with human immunodeficiency virus proteases. W53I/Q55G). 1995 The Journal of biological chemistry Abstract HIV Q55G 5 9 7503549 Inactivation of human immunodeficiency virus type 1 reverse transcriptase by oltipraz: evidence for the formation of a stable adduct. Procion yellow H4R was chosen as the dye-ligand chromatography since it was the most potent and selective inhibitor of RT among seventy reactive dyes that were screened. 1995 Archives of biochemistry and biophysics Abstract HIV H4R 15 18 RT 119 121 7503549 Inactivation of human immunodeficiency virus type 1 reverse transcriptase by oltipraz: evidence for the formation of a stable adduct. Thus, HIV-2 RT as well as wild-type, 38Cys-->Ser, 280Cys-->Ser, and the Cys-->Ser double mutant of HIV-1 RT were purified from the lysates of transformed Escherichia coli strain DH5 alpha (A. 1995 Archives of biochemistry and biophysics Abstract HIV C280S;C38S 50;37 62;48 RT;RT 12;105 14;107 7504715 [Reverse transcriptase gene analysis of HIV-1 mutants cultured in the presence of AZT]. Some of the 22 clones also had other mutations at codon 67 (Asp-->Ser), codon 70 (Lys-->Arg) and codon 219 (Lys-->Glu or Gln). 1993 Kansenshogaku zasshi Abstract HIV K219E 97 120 Asp 60 63 7504715 [Reverse transcriptase gene analysis of HIV-1 mutants cultured in the presence of AZT]. The clones of the isolates obtained from the patients (04 or 05) had mutations at only codon 215 Thr-->Tyr) in both the presence and the absence of AZT. 1993 Kansenshogaku zasshi Abstract HIV T215T 93 106 7507182 Rapid phenotypic reversion of zidovudine-resistant feline immunodeficiency virus without loss of drug-resistant reverse transcriptase. Sequence analysis of the reverse transcriptase (RT)-encoding region from the plaque-purified AZT-resistant FIV revealed a single base change at position 2939, resulting in a Glu-to-Lys substitution at amino acid 202 of the RT. 1994 Journal of virology Abstract HIV E202K 174 215 RT;RT;RT 25;48;223 46;50;225 7507184 Resistance to neutralization by broadly reactive antibodies to the human immunodeficiency virus type 1 gp120 glycoprotein conferred by a gp41 amino acid change. A threonine-for-alanine substitution at position 582 in the gp41 transmembrane envelope glycoprotein of the variant virus was responsible for the neutralization-resistant phenotype (M.S. 1994 Journal of virology Abstract HIV A582T 2 52 Env;gp41 79;60 87;64 7507184 Resistance to neutralization by broadly reactive antibodies to the human immunodeficiency virus type 1 gp120 glycoprotein conferred by a gp41 amino acid change. It is shown here that the change of alanine 582 to threonine specifically confers resistance to neutralizing by antibodies directed against both groups of discontinuous, conserved epitopes related to the CD4 binding site on the gp120 exterior envelope glycoprotein. 1994 Journal of virology Abstract HIV A582T 36 60 Env;gp120 243;228 251;233 7507188 Characterization of mutants of human immunodeficiency virus type 1 that have escaped neutralization by a monoclonal antibody to the gp120 V2 loop. Experimental introduction of the Y177H substitution into the RF V2 loop in the context of the NL4-3 molecular clone re-created the G3-4-resistant phenotype. 1994 Journal of virology Abstract HIV Y177H 33 38 7507188 Characterization of mutants of human immunodeficiency virus type 1 that have escaped neutralization by a monoclonal antibody to the gp120 V2 loop. PCR sequencing of the entire gp120 of the wild-type RF virus and the escape mutants showed that amino acid substitutions had occurred only at two positions, Y177H and L179P, both in V2. 1994 Journal of virology Abstract HIV L179P;Y177H 167;157 172;162 gp120 29 34 7507188 Characterization of mutants of human immunodeficiency virus type 1 that have escaped neutralization by a monoclonal antibody to the gp120 V2 loop. The L179P mutant was not viable. 1994 Journal of virology Abstract HIV L179P 4 9 7509000 Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. The most common mutation with monotherapy, tyrosine to cysteine at residue 181, was prevented from emerging by coadministration of AZT, which resulted in the selection of alternative mutations. 1994 Journal of virology Abstract HIV Y181C 43 78 7509144 Viral resistance to the thiazolo-iso-indolinones, a new class of nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Comparison of the deduced amino acid sequences with the wild-type sequence showed an amino acid change at position 181 (Tyr to Cys). 1993 Antimicrobial agents and chemotherapy Abstract HIV Y181C 115 131 7509370 Zidovudine treatment results in the selection of human immunodeficiency virus type 1 variants whose genotypes confer increasing levels of drug resistance. High level resistance to 3'-azido-3'-deoxythymidine (AZT, zidovudine or Retrovir) is conferred by the presence of four or five mutations (Met-41-->Leu; Asp-67-->Asn; Lys-70-->Arg; Thr-215-->Tyr or Phe; Lys-219-->Gln) in the human immunodeficiency virus (HIV) reverse transcriptase. 1994 The Journal of general virology Abstract HIV D67N;K219Q;K70R;M41L;T215P;T215T 152;202;166;138;180;180 164;215;178;150;200;200 RT;Asp 259;152 280;155 7509634 Sensitivity of HIV-1 reverse transcriptase and its mutants to inhibition by azidothymidine triphosphate. A reverse transcriptase containing a set of four mutations (D67N, K70R, T215Y, K219Q) known to cause resistance to AZT in cell culture assays has a ratio of incorporation that is 0.77 +/- 0.03 times the ratio for the wild-type reverse transcriptase opposite one specific template adenosine. 1994 Biochemistry Abstract HIV D67N;K219Q;K70R;T215Y 60;79;66;72 64;84;70;77 RT;RT 2;227 23;248 7509634 Sensitivity of HIV-1 reverse transcriptase and its mutants to inhibition by azidothymidine triphosphate. In contrast, a hybrid mutant containing the same four mutations that cause resistance to AZT and an additional mutation, Y181C, which by itself causes resistance to the non-nucleoside inhibitor L-697,661 [Sardana et al. 1994 Biochemistry Abstract HIV Y181C 121 126 7509800 Kinetic and mutational analysis of human immunodeficiency virus type 1 reverse transcriptase inhibition by inophyllums, a novel class of non-nucleoside inhibitors. A mutant enzyme in which tyrosine 188 was changed to leucine was cross-resistant to both inophyllum B and TIBO R82913, as was HIV type 2 reverse transcriptase. 1994 The Journal of biological chemistry Abstract HIV Y188L 25 60 RT 137 158 7512165 Mutagenic study of codons 74 and 215 of the human immunodeficiency virus type 1 reverse transcriptase, which are significant in nucleoside analog resistance. A combination of the Thr-215-->Trp with the other AZT resistance mutations Lys-70-->Arg and Met-41-->Leu gave additive resistance. 1994 Journal of virology Abstract HIV T215W 21 34 7512165 Mutagenic study of codons 74 and 215 of the human immunodeficiency virus type 1 reverse transcriptase, which are significant in nucleoside analog resistance. A leucine-to-valine substitution at codon 74 has previously been found to confer dideoxynucleoside resistance. 1994 Journal of virology Abstract HIV L74V 2 44 7512165 Mutagenic study of codons 74 and 215 of the human immunodeficiency virus type 1 reverse transcriptase, which are significant in nucleoside analog resistance. The majority of the new mutants were AZT sensitive, whereas the Thr-215-->Trp mutant was partially resistant (threefold less susceptible). 1994 Journal of virology Abstract HIV T215W 64 77 7512165 Mutagenic study of codons 74 and 215 of the human immunodeficiency virus type 1 reverse transcriptase, which are significant in nucleoside analog resistance. The Thr-215-->Phe virus was less AZT resistant than the Thr-215-->Tyr mutant, both on its own and when each was combined with the Met-41-->Leu mutant. 1994 Journal of virology Abstract HIV M41L;T215P;T215T 130;4;56 142;17;69 7513921 Mutational analysis of residue 190 of human immunodeficiency virus type 1 reverse transcriptase. Double mutants, which contain the Gly 190 Glu mutation together with substitutions that confer resistance to other RT inhibitors, were all shown to possess severely diminished polymerase activity. 1994 Virology Abstract HIV G190E 34 45 Pol;RT 176;115 186;117 7513921 Mutational analysis of residue 190 of human immunodeficiency virus type 1 reverse transcriptase. Notably, the RNA-dependent DNA polymerase activity of the Gly 190 Glu mutant enzyme is drastically diminished with respect to the wild-type RT. 1994 Virology Abstract HIV G190E 58 69 Pol;RT 31;140 41;142 7513921 Mutational analysis of residue 190 of human immunodeficiency virus type 1 reverse transcriptase. S-2720 and other members of the quinoline/quinoxaline class of HIV-1-specific nonnucleoside reverse transcriptase inhibitors (NNRTIs) select for a glycine to glutamate substitution at residue 190 (Gly 190 Glu) of the reverse transcriptase (RT), when drug-resistant viruses are generated in cell culture. 1994 Virology Abstract HIV G190E;G190E 147;197 195;208 NNRTI;RT;NNRTI;RT 78;217;126;240 113;238;132;242 7514016 Characterization of HIV-1 strains isolated from patients treated with TIBO R82913. One of these substitutions, that is, I/V179D (from an untreated patient), conferred a sevenfold reduced RT sensitivity to R82913. 1994 AIDS research and human retroviruses Abstract HIV I179D;V179D 37;37 44;44 RT 104 106 7514016 Characterization of HIV-1 strains isolated from patients treated with TIBO R82913. The drug-resistant strain in this patient emerged after 3 weeks of treatment and was due to the Y188L mutation in its RT. 1994 AIDS research and human retroviruses Abstract HIV Y188L 96 101 RT 118 120 7514855 Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine. Four of these clinical samples were also demonstrated to possess the Met-184-->Val mutation, and one of them possessed both the Lys-65-->Arg and Met-184-->Val substitutions. 1994 Antimicrobial agents and chemotherapy Abstract HIV M184V 69 82 7514856 Resistance to 2',3'-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase. Characterization of this virus confirmed that the RT Lys-65-->Arg substitution was necessary and sufficient for a fourfold increase in the ddC 50% inhibitory concentration, as well as for resistance to didanosine (2',3'-dideoxyinosine [ddI]). 1994 Antimicrobial agents and chemotherapy Abstract HIV K65R 53 65 RT 50 52 7514856 Resistance to 2',3'-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase. Lys-65-->Arg and virus resistance to ddC and ddI also developed during therapy in isolates from one ddC-treated patient and two ddI-treated patients. 1994 Antimicrobial agents and chemotherapy Abstract HIV K65R 0 12 7514856 Resistance to 2',3'-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase. Results of mutant enzyme studies are consistent with Lys-65-->Arg leading to changes in binding of the triphosphate forms of these nucleoside analogs to the RT. 1994 Antimicrobial agents and chemotherapy Abstract HIV K65R 53 65 RT 157 159 7515055 Subunit-selective mutagenesis of Glu-89 residue in human immunodeficiency virus reverse transcriptase. Contribution of p66 and p51 subunits to nucleoside analog sensitivity, divalent cation preference, and steady state kinetic properties. The E89G alteration in the human immunodeficiency virus type 1 reverse transcriptase has been shown to confer resistance to nucleoside analogs and a loss of magnesium cation preference (Prasad, V.R., Lowy, I., De Los Santos, T., Chiang, L., and Goff, S.P. 1994 The Journal of biological chemistry Abstract HIV E89G 4 8 RT 63 84 7515055 Subunit-selective mutagenesis of Glu-89 residue in human immunodeficiency virus reverse transcriptase. Contribution of p66 and p51 subunits to nucleoside analog sensitivity, divalent cation preference, and steady state kinetic properties. The wild type reverse transcriptase heterodimer, chimeric reverse transcriptases that contain the E89G alteration in one of the subunits (p66wt/p51m and p66m/p51wt), and the mutant enzyme (p66m/p51m) were prepared. 1994 The Journal of biological chemistry Abstract HIV E89G 98 102 RT;RT 14;58 35;80 7515182 Sensitivity of wild-type human immunodeficiency virus type 1 reverse transcriptase to dideoxynucleotides depends on template length; the sensitivity of drug-resistant mutants does not. Wild-type HIV-1 RT and two nucleoside-resistant variants, Leu74-->Val and Glu89-->Gly, have been analyzed to determine the basis of resistance. 1994 Proc Natl Acad Sci U S A Abstract HIV E89G;L74V 74;58 85;69 RT 16 18 7517553 Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants. HIV-1 mutant that emerged under the latter conditions contained a Cys181-->Ile substitution in their RT [(LC181I)RT]. 1994 Proc Natl Acad Sci U S A Abstract HIV C181I 66 78 RT;RT 101;113 103;115 7517553 Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants. In contrast, cells infected with a virus mutant that expresses a Tyr181-->Cys substitution in its RT [(Y181C)RT] were not protected by nevirapine and TIBO and were only temporarily protected by BHAP. 1994 Proc Natl Acad Sci U S A Abstract HIV Y181C;Y181C 103;65 108;77 RT;RT 98;109 100;111 7517553 Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants. Mutant HIV-1 that expresses a Glu138-->Lys substitution in its RT [(E138K)RT] is resistant to the HIV-1-specific RT inhibitor 2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)pyrimidine (TSAO). 1994 Proc Natl Acad Sci U S A Abstract HIV E138K;E138K 68;30 73;42 RT;RT;RT 63;74;113 65;76;115 7517553 Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants. Since a (Y181F)RT HIV mutant strain was isolated from cells infected with (Y181C)RT HIV-1 and treated with BHAP, we postulate that the Ile codon was derived from a Cys-->Phe transversion mutation (TGT-->TTT), followed by a Phe-->Ile transversion mutation (TTT-->ATT). 1994 Proc Natl Acad Sci U S A Abstract HIV Y181C;Y181F 75;9 80;14 RT;RT 15;81 17;83 7517553 Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants. When recombinant (C181I)RT was evaluated for susceptibility to the HIV-1-specific RT inhibitors, it was resistant to all inhibitors except the HEPT compounds. 1994 Proc Natl Acad Sci U S A Abstract HIV C181I 18 23 RT;RT 24;82 26;84 7517668 Sensitivity of (138 Glu-->Lys) mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors. In contrast, 181 Tyr-->Cys mutated RT lost sensitivity to all HIV-1-specific inhibitors. 1994 Biochemical and biophysical research communications Abstract HIV Y181C 13 26 RT 35 37 7517668 Sensitivity of (138 Glu-->Lys) mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors. There was a close correlation between the sensitivity/resistance pattern of HIV-1-specific inhibitors against mutated (138 Glu-->Lys) recombinant HIV-1 RT and mutant virus strains selected for resistance against TSAO-m3T in cell culture and proven to contain the 138-Lys mutation as the sole mutation within the amino acid 50-270 region of their RT. 1994 Biochemical and biophysical research communications Abstract HIV E138K 119 132 RT;RT 152;346 154;348 7518454 Mutagenesis of the conserved aspartic acid 443, glutamic acid 478, asparagine 494, and aspartic acid 498 residues in the ribonuclease H domain of p66/p51 human immunodeficiency virus type I reverse transcriptase. Expression and biochemical analysis. Analysis of selected D443/D498 double mutants suggested that the destabilization caused by the D498N mutation could be suppressed by the formation of a new hydrogen bond between Asn498 and Asn443. 1994 The Journal of biological chemistry Abstract HIV D498N 95 100 7518454 Mutagenesis of the conserved aspartic acid 443, glutamic acid 478, asparagine 494, and aspartic acid 498 residues in the ribonuclease H domain of p66/p51 human immunodeficiency virus type I reverse transcriptase. Expression and biochemical analysis. The only mutation in the former class was D443A, whereas those in the latter included D443E, E478D, E478Q, D498E, D443A/D498N, D443E/D498N, D443Q/D498N, N494A, N494D, and N494Q. 1994 The Journal of biological chemistry Abstract HIV D443A;D443A;D443E;D443E;D443Q;D498E;D498N;D498N;D498N;E478D;E478Q;N494A;N494D;N494Q 42;114;86;127;140;107;120;133;146;93;100;153;160;171 47;119;91;132;145;112;125;138;151;98;105;158;165;176 7519811 Polymerase chain reaction (PCR) as a diagnostic tool in HIV infection. In an untreated patient we identified an amino acid variant (I/V 179D) involved in a 7-fold reduced sensitivity to TIBO. 1994 Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie Abstract HIV V179D 61 69 7519811 Polymerase chain reaction (PCR) as a diagnostic tool in HIV infection. In HIV-1 isolates from TIBO R82913-treated patients we identified two amino acid mutations (V108I and Y188L) involved in resistance (more than 100-fold reduced sensitivity). 1994 Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie Abstract HIV V108I;Y188L 92;102 98;107 7523383 Resistance of HIV-1 reverse transcriptase against [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2''-dioxide)] (TSAO) derivatives is determined by the mutation Glu138-->Lys on the p51 subunit. When the TSAO-specific resistance mutation Glu138-->Lys was introduced solely in the p51 subunit of the RT p66/p51 heterodimer, the enzyme proved completely resistant to TSAO-m3T but retained full sensitivity to TIBO R82150 and ddGTP. 1994 The Journal of biological chemistry Abstract HIV E138K 43 55 RT 104 106 7524439 Enzymatic properties and sensitivity to inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with Glu-138-->Arg and Tyr-188-->His mutations. As compared to wild type RT, a reduction in catalytic efficiency and turn over number was observed, especially for the Tyr-188-->His mutant. 1994 Antiviral research Abstract HIV Y188H 119 132 RT 25 27 7525567 The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. HIV-1 cross-resistance to ddC/3TC/ddI resulting from the K65R mutation may therefore involve selective alterations in substrate/inhibitor recognition. 1994 The Journal of biological chemistry Abstract HIV K65R 57 61 7525567 The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. The K65R mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) encodes cross-resistance to 2',3'-dideoxycytidine (ddC), 2',3'-dideoxy-3'-thiacytidine (3TC), and 2',3'-dideoxyinosine (ddI). 1994 The Journal of biological chemistry Abstract HIV K65R 4 8 RT;RT 65;88 86;90 7525567 The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. We characterized the in vitro sensitivities of recombinant wild type (wt) and K65R mutant RT to dideoxynucleoside triphosphate (ddNTP) inhibitors, using a variety of primer-templates. 1994 The Journal of biological chemistry Abstract HIV K65R 78 82 RT 90 92 7525567 The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. With a heteropolymeric primer-template, the K65R mutant showed 10-fold reduced sensitivities to ddCTP, 3TCTP, and ddATP, and 4-fold reduced sensitivity to AZTTP, compared to wt. 1994 The Journal of biological chemistry Abstract HIV K65R 44 48 7525567 The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. With poly(rA)-oligo(dT), the K65R mutant showed slight increases in Ki for ddTTP and 3'-azido, 3'-deoxythymidine triphosphate (AZTTP) compared to wt RT, but neither wt nor K65R RT was inhibited by ddCTP or ddATP. 1994 The Journal of biological chemistry Abstract HIV K65R;K65R 29;172 33;176 RT;RT 149;177 151;179 7525567 The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. With poly(rI)-oligo(dC), the K65R mutant showed a 2-fold increase in Km for dCTP and a 20-fold increase in Ki for ddCTP compared to wt, whereas ddATP, ddTTP, and AZTTP failed to inhibit either enzyme. 1994 The Journal of biological chemistry Abstract HIV K65R 29 33 7527086 Resistance to nucleoside analogs of selective mutants of human immunodeficiency virus type 2 reverse transcriptase. We have modified, by site-directed mutagenesis, several of those amino acid residues so that their equivalent substitutions in HIV-1 RT have led to the formation of HIV-1 RT variants with the highest degree of resistance to dideoxynucleoside triphosphates (i.e., Glu-89-->Gly, Leu-74-->Val, and Ser-215-->Tyr [which is comparable to the Thr-215-->Tyr mutation of HIV-1 RT] and the double mutations Glu-89-->Gly/Ser-215-->Tyr and and Leu-74-->Val/Ser-215-->Tyr). 1995 Journal of virology Abstract HIV E89G;G89G;L74V;S215T;S215T;T215T 263;398;433;411;446;337 275;410;445;424;459;350 RT;RT;RT 133;171;369 135;173;371 7529011 Subunit specificity of mutations that confer resistance to nonnucleoside inhibitors in human immunodeficiency virus type 1 reverse transcriptase. However, there was one mutation, E138K, that conferred drug resistance when the mutation was present in the p51 subunit. 1994 Antimicrobial agents and chemotherapy Abstract HIV E138K 33 38 7529011 Subunit specificity of mutations that confer resistance to nonnucleoside inhibitors in human immunodeficiency virus type 1 reverse transcriptase. The corresponding heterodimer with the E138K mutation in the p66 subunit and a wild-type p51 subunit remained sensitive to the inhibitors. 1994 Antimicrobial agents and chemotherapy Abstract HIV E138K 39 44 7530396 Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs. By contrast, the dissociation constants of K296R(1-551) and Wt(1-243) for TAR(1-82) RNA were both about 1 x 10(-7) M. 1995 Virology Abstract HIV K296R 43 48 7530396 Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs. The dissociation constant for VAI RNA was approximately 2 x 10(-9) M for both the K296R(1-551) and Wt(1-243) proteins. 1995 Virology Abstract HIV K296R 82 87 7530396 Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs. The K64E mutation significantly impaired the VAI RNA-binding activity as measured with the full-length double-point mutant PKR protein, K64E/K296R(1-551). 1995 Virology Abstract HIV K296R;K64E;K64E 141;4;136 146;8;140 7530396 Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs. The N-terminal 243 amino acid residue form of PKR [Wt(1-243)] bound VAI RNA with similar affinity as the 551 amino acid residue full-length catalytic mutant [K296R(1-551)]. 1995 Virology Abstract HIV K296R 158 163 7530396 Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs. The N-terminal R-domain truncation Wt(1-243) and the full-length catalytic mutant K296R(21-551) were analyzed for their abilities to bind adenovirus VAI RNA, human immunodeficiency virus TAR RNA, and the synthetic homopolymer pI:pC RNA. 1995 Virology Abstract HIV K296R 82 87 PI 226 228 7530396 Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs. Using a gel-shift competition assay, the dissociation constants of K296R(1-551) and Wt(1-243) for VAI(1-160) RNA and pI:pC RNA were comparable. 1995 Virology Abstract HIV K296R 67 72 PI 117 119 7530932 Inhibition of human immunodeficiency virus type 1 reverse transcriptase by the 5'-triphosphate beta enantiomers of cytidine analogs. By using sequencing analysis, L-ddCTP and L-FddCTP exhibited DNA chain-terminating activities toward the parental HIV-1 RT, whereas they were not a substrate for the mutant M184V HIV-1 RT.L-ddC and L-FddC did not inhibit the mitochondrial DNA content of human cells up to a concentration of 10 microM, whereas D-ddC and D-FddC decreased the mitochondrial DNA content by 90% at concentrations of 1 and 10 microM, respectively. 1994 Antimicrobial agents and chemotherapy Abstract HIV M184V 173 178 RT;RT 120;185 122;187 7530932 Inhibition of human immunodeficiency virus type 1 reverse transcriptase by the 5'-triphosphate beta enantiomers of cytidine analogs. Use of the mutant RT at position 184 (substitution of methionine to valine [M184V]), which is associated with resistance to beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) and beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC), resulted in significant increases (50- to 60-fold) in Ki values for L-ddCTP and L-FddCTP, whereas the elevation in Ki values for D-ddCTP and D-FddCTP was moderate (2-fold). 1994 Antimicrobial agents and chemotherapy Abstract HIV M184V 76 81 RT 18 20 7532595 Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Active HIV-1 RT mutants H235W, D237T, and H235W/D237T/T240K, containing substitutions from HIV-2 RT, were also cloned, expressed, and purified. 1995 FEBS letters Abstract HIV D237T;H235W;T240K;D237T;H235W 48;42;54;31;24 53;47;59;36;29 RT;RT 13;97 15;99 7532595 Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. BHAP-resistant HIV-1 is sensitized to other classes of nonnucleoside RT inhibitors and this has been primarily attributed to a proline-to-leucine substitution at amino acid 236 (P236L) of HIV-1 RT. 1995 FEBS letters Abstract HIV P236L;P236L 178;127 183;176 RT;RT 69;194 71;196 7532595 Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. The HIV-1 RT mutants bearing single (H235W; D237T) or multiple (H235W/D237T/T240K) HIV-2 RT substitutions around the conserved P236 conferred little resistance or sensitization to these RT inhibitors. 1995 FEBS letters Abstract HIV D237T;H235W;T240K;D237T;H235W 70;64;76;44;37 75;69;81;49;42 RT;RT;RT 10;89;186 12;91;188 7532595 Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. These results suggest alterations in the shape of the binding pocket as the mechanism by which the P236L mutation confers resistance to the BHAPs and sensitization to L-697,661. 1995 FEBS letters Abstract HIV P236L 99 104 7532595 Mechanism of resistance to U-90152S and sensitization to L-697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. To understand the basis for the in vitro sensitization-resistance phenomenon, single base pair mutations at amino acid P236 in HIV-1 RT were introduced to obtain P236L, P236T, P236H, P236R, and P236A HIV-1 RT mutants. 1995 FEBS letters Abstract HIV P236A;P236H;P236L;P236R;P236T 194;176;162;183;169 199;181;167;188;174 RT;RT 133;206 135;208 7533854 Characterization of neutralization epitopes in the V2 region of human immunodeficiency virus type 1 gp120: role of glycosylation in the correct folding of the V1/V2 domain. A number of MAbs (C108G, G3-4, 684-238, SC258, 11/68b, 38/66a, 38/66c, 38/62c, and CRA3) that did not bind with high affinity to peptides immunoprecipitated a fusion glycoprotein expressing the V1/V2 domain of HXB2 gp120 in the absence of other human immunodeficiency virus sequences, establishing that their epitopes were fully specified within this region. 1995 Journal of virology Abstract HIV C108G 18 23 gp120 215 220 7533854 Characterization of neutralization epitopes in the V2 region of human immunodeficiency virus type 1 gp120: role of glycosylation in the correct folding of the V1/V2 domain. Both C108G and MAbs directed against conformational epitopes reacted with large fractions of the fully glycosylated molecules but with only small fractions of the incompletely glycosylated molecules. 1995 Journal of virology Abstract HIV C108G 5 10 7533854 Characterization of neutralization epitopes in the V2 region of human immunodeficiency virus type 1 gp120: role of glycosylation in the correct folding of the V1/V2 domain. Mutation of glycosylation site 160 destroyed the C108G epitope but increased the fraction of the molecules that presented the conformational epitopes, while mutation of the highly conserved glycosylation site at position 156 greatly diminished the expression of the conformational epitopes and increased expression of the C108G epitope. 1995 Journal of virology Abstract HIV C108G;C108G 49;322 54;327 7533854 Characterization of neutralization epitopes in the V2 region of human immunodeficiency virus type 1 gp120: role of glycosylation in the correct folding of the V1/V2 domain. These include rodent antibodies directed against linear and conformational epitopes and a chimpanzee MAb, C108G, with extremely potent neutralizing activity directed against a glycan-dependent epitope. 1995 Journal of virology Abstract HIV C108G 106 111 7534421 Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. A set of mutations [Ala-62-->Val(A62V), V75I, F77L, F116Y, and Q151M] in the polymerase domain of reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) confers on the virus a reduced sensitivity to multiple antiretroviral dideoxynucleosides and has been seen in HIV-1 variants isolated from patients receiving combination chemotherapy with 3'-azido-3'-deoxythymidine (AZT) plus 2',3'-dideoxycytidine (ddC) or 2',3'-dideoxyinosine (ddI). 1995 Proc Natl Acad Sci U S A Abstract HIV A62V;A62V;F116Y;F77L;Q151M;V75I 33;20;52;46;63;40 37;32;57;50;68;44 RT;Pol;RT 98;77;121 119;87;123 7534421 Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Detailed analysis of HIV-1 strains isolated at various times during therapy showed that the Q151M mutation developed first in vivo, at the time when the viremia level suddenly increased, followed by the F116Y and F77L mutations. 1995 Proc Natl Acad Sci U S A Abstract HIV F116Y;F77L;Q151M 203;213;92 208;217;97 7535037 New tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione derivatives are potent inhibitors of human immunodeficiency virus type 1 replication and are synergistic with 2',3'-dideoxynucleoside analogs. Whereas an HIV-1 strain containing the Leu-100-->Ile mutation in the RT gene is about 400-fold less susceptible, R86183 still inhibits the replication of an HIV-1 strain containing the Tyr-181-->Cys RT mutation by 50% at a concentration of 130 nM. 1994 Antimicrobial agents and chemotherapy Abstract HIV L100I;Y181C 39;185 52;198 RT;RT 69;199 71;201 7535864 Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity. The catalytic efficiency (kcat) of the HIV-1 protease is decreased 4-fold when threonine 26 is replaced by serine (T26S) and approximately 50-fold when alanine 28 is replaced by serine (A28S). 1995 Journal of virology Abstract HIV A28S;A28S;T26S;T26S 186;152;115;79 190;184;119;113 PR 45 53 7535864 Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity. The results show that virions containing the T26S protease variant, in which only 25% of the protease is active, are very similar to wild-type virions, although slight reductions in infectivity are observed. 1995 Journal of virology Abstract HIV T26S 45 49 PR;PR 50;93 58;101 7535864 Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity. Virions containing the A28S protease variant are not infectious, even though a limited amount of polyprotein processing does occur. 1995 Journal of virology Abstract HIV A28S 23 27 PR 28 36 7535930 Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. A lysine-to-arginine substitution at amino acid 65 (K65R) in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is associated with resistance to 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI), and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC). 1995 Proc Natl Acad Sci U S A Abstract HIV K65R;K65R 52;2 56;50 RT;RT 105;128 126;130 7535930 Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. Both the K65R mutant RT and wild-type RT had similar processive activity. 1995 Proc Natl Acad Sci U S A Abstract HIV K65R 9 13 RT;RT 21;38 23;40 7535930 Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. However, the frequency of dideoxynucleoside triphosphate (ddNTP)-induced chain termination was decreased at certain guanines but not others in reactions catalyzed by K65R RT. 1995 Proc Natl Acad Sci U S A Abstract HIV K65R 166 170 RT 171 173 7535930 Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. The K65R and K65R/M184V RTs showed significantly decreased chain-termination effects during polymerization with the 5'-triphosphates of ddC, 3TC, 2',3'-dideoxyadenosine, and AZT (3'-azido-3'-deoxythymidine) in comparison with wild-type RT. 1995 Proc Natl Acad Sci U S A Abstract HIV K65R;K65R;M184V 4;13;18 8;17;23 RT;RT 24;236 27;238 7535930 Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. These results indicate that decreased chain termination of K65R RT in the presence of ddNTPs is consistent with data obtained in viral replication assays. 1995 Proc Natl Acad Sci U S A Abstract HIV K65R 59 63 RT 64 66 7535930 Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs. To further characterize the molecular basis of such resistance, we expressed the pp6/p51 heterodimer of wild-type RT, K65R mutated RT, and a doubly mutated (K65R/M184V) RT in Escherichia coli and assessed the characteristics of nucleotide incorporation and chain termination in cell-free reverse transcription reactions in the presence and absence of various nucleoside triphosphate analogs. 1995 Proc Natl Acad Sci U S A Abstract HIV K65R;K65R;M184V 118;157;162 122;161;167 RT;RT;RT;RT 288;114;131;169 309;116;133;171 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. However, unlike the wild-type enzyme, the Q151A mutant failed to catalyze the nucleotidyl transferase reaction onto the primer terminus of the covalently immobilized template-primer. 1995 Biochemistry Abstract HIV Q151A 42 47 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. In contrast, p66Q151A/p51WT is indistinguishable from Q151A (mutated in both subunits). 1995 Biochemistry Abstract HIV Q151A;Q151A 16;54 21;59 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. In order to define the role of Gln151 in the polymerase function of HIV-1 RT, we carried out site-directed mutagenesis of this residue by substituting it with a conserved (Q151N) and a nonconserved residue (Q151A). 1995 Biochemistry Abstract HIV Q151A;Q151N 207;172 212;177 Pol;RT 45;74 55;76 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. Most interestingly, the affinity of the Q151A mutant for dNTP substrate remained unchanged with RNA templates, but a significant increase in Km was noted with the DNA template. 1995 Biochemistry Abstract HIV Q151A 40 45 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. Q151N exhibited properties analogous to those of the wild-type enzyme, while Q151A has severely impaired polymerase activity. 1995 Biochemistry Abstract HIV Q151A;Q151N 77;0 82;5 Pol 105 115 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. The binding affinity of Q151A for DNA remained unchanged, as judged by photoaffinity cross-linking. 1995 Biochemistry Abstract HIV Q151A 24 29 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. The effects of the mutation seem to be through Q151 of the p66 catalytic subunit, as p66WTt/p51Q151A retains the wild-type kinetic constants and nucleotidyl transferase activity. 1995 Biochemistry Abstract HIV Q151A 95 100 7539293 Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. The Q151A mutant exhibited a 15-100-fold reduction in kcat with RNA [poly(rC) and poly(rA)] templates, while only a 5-fold reduction could be seen with the DNA [poly(dC)] template. 1995 Biochemistry Abstract HIV Q151A 4 9 7540384 Differential activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives against different human immunodeficiency virus type 1 mutant strains. A series of 23 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives that were highly potent inhibitors of wild-type human immunodeficiency virus type 1 strain IIIB (HIV-1/IIIB) replication in CEM cells were evaluated against a panel of HIV-1 mutant strains containing the replacement of leucine by isoleucine at position 100 (100-Leu-->Ile), 103-Lys-->Asn, 106-Val-->Ala, 138-Glu-->Lys, 181-Tyr-->Cys, 181-Tyr-->Ile, or 188-Tyr-->His in their reverse transcriptase (RT). 1995 Antimicrobial agents and chemotherapy Abstract HIV E138K;K103N;L100I;V106A;Y181C;Y181I 381;351;296;366;396;411 394;364;333;379;409;424 RT;RT 452;475 473;477 7540784 Resistance to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives is generated by mutations at multiple sites in the HIV-1 reverse transcriptase. The virus isolate resistant to NSC 648400 had a single amino acid change in the reverse transcriptase (Y181C) which resulted in cross-resistance to all of the nonnucleoside reverse transcriptase inhibitors evaluated, with the exception of calanolide A. 1995 Virology Abstract HIV Y181C 103 108 NNRTI;RT 159;80 194;101 7540784 Resistance to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives is generated by mutations at multiple sites in the HIV-1 reverse transcriptase. The virus isolate selected in the presence of HEPT exhibited a single amino acid change (P236L) which was not cross-resistant to other nonnucleoside RT inhibitors tested with the exception of the two HEPT derivatives. 1995 Virology Abstract HIV P236L 89 94 RT 149 151 7541135 A molecular sensor system based on genetically engineered alkaline phosphatase. Hybrid proteins were constructed by using wild-type AP and point mutants of AP [Asp-101 --> Ser (D101S) and Asp-153 --> Gly (D153G)]. 1995 Proc Natl Acad Sci U S A Abstract HIV D101S;D101S;D153G;D153G 80;97;108;125 95;102;123;130 Asp;Asp 80;108 83;111 7542860 Novel mutations in reverse transcriptase of human immunodeficiency virus type 1 reduce susceptibility to foscarnet in laboratory and clinical isolates. DNA sequence analysis of RT clones from resistant virus revealed the coexistence of two mutations in all clones: Gln-161 to Leu (CAA to CTA) and His-208 to Tyr (CAT to TAT). 1995 Antimicrobial agents and chemotherapy Abstract HIV H208Y;Q161L 145;113 159;127 Tat;RT 168;25 171;27 7542860 Novel mutations in reverse transcriptase of human immunodeficiency virus type 1 reduce susceptibility to foscarnet in laboratory and clinical isolates. Sequence analysis of six clinical HIV-1 isolates showing reduced susceptibility to foscarnet revealed the Tyr-208 mutation in two, the Leu-161 mutation in one, and a Trp-88-to-Ser or -Gly mutation in four isolates. 1995 Antimicrobial agents and chemotherapy Abstract HIV W88S 166 179 7542860 Novel mutations in reverse transcriptase of human immunodeficiency virus type 1 reduce susceptibility to foscarnet in laboratory and clinical isolates. The Gln-161-to-Leu mutation may affect the structure of the dNTP binding site and its affinity for foscarnet. 1995 Antimicrobial agents and chemotherapy Abstract HIV Q161L 4 18 7543283 Divalent cation modulation of the ribonuclease functions of human immunodeficiency virus reverse transcriptase. Enzyme altered at the p66 residue Glu478 (Glu478-->Gln478), which participates in metal ion binding, is completely inactive in Mg2. 1995 Biochemistry Abstract HIV E478Q 42 57 7544302 Simultaneous mutations at Tyr-181 and Tyr-188 in HIV-1 reverse transcriptase prevents inhibition of RNA-dependent DNA polymerase activity by the bisheteroarylpiperazine (BHAP) U-90152s. Construction and in vitro analysis of double mutants Y181I/Y188L and Y181C/Y188L of HIV-1 RT showed > 150-fold resistance to U-90152S. 1995 FEBS letters Abstract HIV Y181C;Y181I;Y188L;Y188L 69;53;59;75 74;58;64;80 RT 90 92 7544302 Simultaneous mutations at Tyr-181 and Tyr-188 in HIV-1 reverse transcriptase prevents inhibition of RNA-dependent DNA polymerase activity by the bisheteroarylpiperazine (BHAP) U-90152s. The bisheteroarylpiperazine (BHAP) U-90152S, a highly specific inhibitor (IC50, 0.29 +/- 0.01 microM) of HIV-1 RT, inhibited the recombinant Y181I and Y188L HIV-1 RT mutants with IC50 values of 3.6 +/- 0.15 microM and 0.71 +/- 0.02 microM, respectively. 1995 FEBS letters Abstract HIV Y181I;Y188L 141;151 146;156 RT;RT 111;163 113;165 7544302 Simultaneous mutations at Tyr-181 and Tyr-188 in HIV-1 reverse transcriptase prevents inhibition of RNA-dependent DNA polymerase activity by the bisheteroarylpiperazine (BHAP) U-90152s. The replacement of either Tyr-181 or Tyr-188 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) by the corresponding HIV-2 RT amino acids Ile-181 or Leu-188 is known to result in active mutant enzymes (Y181I; Y188L) with virtual loss of sensitivity towards three structural classes of nonnucleoside RT inhibitors; L-697,661, nevirapine, and TIBO R82913. 1995 FEBS letters Abstract HIV Y181I;Y188L 225;232 230;237 RT;RT;RT;RT 92;115;146;322 113;117;148;324 7544345 Site-directed mutagenesis of arginine 72 of HIV-1 reverse transcriptase. Catalytic role and inhibitor sensitivity. Most interestingly, we noted a large difference in the rate constant of the first and second nucleotide incorporation by R72A, suggesting that Arg72 participates in the reaction after the formation of the first phosphodiester bond. 1995 The Journal of biological chemistry Abstract HIV R72A 121 125 7544345 Site-directed mutagenesis of arginine 72 of HIV-1 reverse transcriptase. Catalytic role and inhibitor sensitivity. Support for this proposal is obtained from the observation that the R72A mutant (i) exhibited a pronounced translocation defect in the processivity analysis, (ii) lacked the ability to catalyze pyrophosphorolysis, and (iii) showed complete resistance to phosphonoformate, an analog of PPi.Arg72 is the first residue of HIV-1 RT proposed to be involved in the pyrophosphate binding/removal function of RT. 1995 The Journal of biological chemistry Abstract HIV R72A 68 72 RT;RT 325;401 327;403 7544345 Site-directed mutagenesis of arginine 72 of HIV-1 reverse transcriptase. Catalytic role and inhibitor sensitivity. Two mutant proteins (R72A and R72K) were purified and characterized. 1995 The Journal of biological chemistry Abstract HIV R72A;R72K 21;30 26;34 7545295 Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. I1Y sensitized HLA-A 0201-expressing target cells for wild-type pol-specific CTL lysis as well as wild-type pol. 1995 Proc Natl Acad Sci U S A Abstract HIV I1Y 0 3 Pol;Pol 64;108 67;111 7545295 Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. I1Y stimulated a higher wild-type pol-specific CTL response than wild-type pol in all three donors. 1995 Proc Natl Acad Sci U S A Abstract HIV I1Y 0 3 Pol;Pol 34;75 37;78 7545295 Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. Peripheral blood lymphocytes from three HLA-A2 HIV-seropositive individuals were stimulated in vitro with I1Y and wild-type pol. 1995 Proc Natl Acad Sci U S A Abstract HIV I1Y 106 109 Pol 124 127 7545295 Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. Surprisingly, I1Y significantly increased the HLA-A 0201-peptide complex stability at the cell surface. 1995 Proc Natl Acad Sci U S A Abstract HIV I1Y 14 17 7545295 Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. The peptide with the P1 substitution of tyrosine for isoleucine (I1Y) showed a binding affinity for HLA-A 0201 similar to that of the wild-type pol peptide in a cell lysate assembly assay. 1995 Proc Natl Acad Sci U S A Abstract HIV I1Y 65 68 Pol 144 147 7545295 Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. Thus, I1Y may be an "improved" epitope for use as a CTL-based human immunodeficiency virus vaccine component. 1995 Proc Natl Acad Sci U S A Abstract HIV I1Y 6 9 7545854 Characterisation of foscarnet-resistant strains of human immunodeficiency virus type 1. The reverse transcriptase of foscarnet-resistant strains had unique substitutions Glu89-Lys, Leu92-Ile, or Ser156-Ala, the third being associated with six polymorphic changes. 1995 Virology Abstract HIV E89K;L92I;S156A 82;93;107 91;102;117 RT 4 25 7559526 Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2',3'-dideoxynucleoside 5'-triphosphates. A set of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the polymerase domain of reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1), which confers on the virus a reduced sensitivity to multiple therapeutic dideoxynucleosides (ddNs), has been identified. 1995 The Journal of biological chemistry Abstract HIV A62V;F116Y;F77L;Q151M;V75I 25;43;37;54;31 29;48;41;59;35 RT;Pol;RT 89;68;112 110;78;114 7559526 Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2',3'-dideoxynucleoside 5'-triphosphates. A single mutation, Q151M, which developed first among the five mutations in patients receiving therapy, most profoundly reduced the sensitivity of RT to multiple ddN 5'-triphosphate (ddNTPs). 1995 The Journal of biological chemistry Abstract HIV Q151M 19 24 RT 147 149 7559526 Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2',3'-dideoxynucleoside 5'-triphosphates. Addition of other mutations to Q151M further reduced the sensitivity of RT to ddNTPs. 1995 The Journal of biological chemistry Abstract HIV Q151M 31 36 RT 72 74 7568151 Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo. A catalytically inactive mutant of PKR with a single amino acid substitution (K296R) was found to dimerize in vivo, and a mutant with a deletion of the catalytic domain of PKR retained the ability to dimerize. 1995 Proc Natl Acad Sci U S A Abstract HIV K296R 78 83 7576926 Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959. Molecular analysis of the mutations underlying resistance revealed a multistep mechanism in which an amino acid exchange was common to all resistant isolates, and in all experiments preceded further exchanges at position 90 (leucine to methionine) and/or at position 54 (isoleucine to valine). 1995 AIDS research and human retroviruses Abstract HIV I54V;L90M 267;221 292;247 7576926 Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959. The primary event (Gly-48 to valine) occurs at the hinge of the flaps of the proteinase, thus hampering entry of the inhibitor to the active center and suggesting steric hindrance. 1995 AIDS research and human retroviruses Abstract HIV G48V 19 35 7588629 A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein. A mutant Fyn SH3 with a single amino acid substitution (R96I) in its RT loop had an affinity (KD 380 nM) for Nef comparable with that of Hck SH3. 1995 The EMBO journal Abstract HIV R96I 56 60 Nef;RT 109;69 112;71 7594706 Development of zidovudine resistance mutations in patients receiving prolonged didanosine monotherapy. However, after prolonged ddI monotherapy, mutations associated with zidovudine resistance (M41L, D67N, K70R, and/or T215Y) were detected in HIV-1 isolates from both patients. 1995 The Journal of infectious diseases Abstract HIV D67N;K70R;M41L;T215Y 97;103;91;116 101;107;95;121 7604010 Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120. Apparently, F43I associates with wtCD4 oligomers and interferes with the formation of functional class II MHC binding structures. 1995 Proc Natl Acad Sci U S A Abstract HIV F43I 12 16 7604010 Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120. Expression of F43I results in a dominant negative effect: no class II MHC binding is observed even though wtCD4 expression is preserved. 1995 Proc Natl Acad Sci U S A Abstract HIV F43I 14 18 7604010 Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120. In contrast, F43I does not affect the binding of gp120 to wtCD4, implying that gp120 binds to a CD4 monomer. 1995 Proc Natl Acad Sci U S A Abstract HIV F43I 13 17 gp120;gp120 49;79 54;84 7604010 Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120. To test this possibility, we transfected the F43I CD4 mutant, which is incapable of binding to class II MHC or human immunodeficiency virus (HIV) gp120, into COS-7 cells together with wild-type CD4 (wtCD4). 1995 Proc Natl Acad Sci U S A Abstract HIV F43I 45 49 gp120 146 151 7605797 The amino-terminal peptide of HIV-1 glycoprotein 41 fuses human erythrocytes. Here, a synthetic peptide (FP; 23 amino acid residues 519-541) corresponding to the N-terminus of HIV-1 gp41, and also a FP analog (FP526L/R) with Arg replacing Leu-526, were prepared with solid phase techniques. 1995 Biochimica et biophysica acta Abstract HIV R526L 147 168 gp41 104 108 7605797 The amino-terminal peptide of HIV-1 glycoprotein 41 fuses human erythrocytes. Since the fusogenic potency of FP and FP526L/R parallels earlier gp41 mutagenesis studies showing that substitution of Arg for Leu-526 blocks fusion activity, these data suggest that the N-terminal gp41 domain in intact HIV participates in fusion. 1995 Biochimica et biophysica acta Abstract HIV L526R 119 134 gp41;gp41 65;198 69;202 7618279 Effects of mutations in constant regions 3 and 4 of envelope of simian immunodeficiency virus. Only one of the C4 mutations, 441W-->R, resulted in greatly decreased binding to sCD4 while retaining normal processing of gp160. 1995 Virology Abstract HIV W441R 30 38 gp160 123 128 7618285 Amino acid substitutions in the V3 loop are responsible for adaptation to growth in transformed T-cell lines of a primary human immunodeficiency virus type 1. A T-cell-line-tropic, syncytium-inducing, sCD4- and serum neutralization-sensitive variant (R3H) of the macrophage-tropic, non-syncytium-inducing, sCD4- and serum neutralization-resistant molecular clone HIV-1SF162 was obtained by passage through the T-cell line HUT 78. 1995 Virology Abstract HIV R3H 92 95 7618285 Amino acid substitutions in the V3 loop are responsible for adaptation to growth in transformed T-cell lines of a primary human immunodeficiency virus type 1. Sequence analyses of the V1-V5 regions of envelope gp120 of the variant R3H revealed amino acid substitutions in the V3 (amino acids 307, 312) and V4 (amino acid 390) domains. 1995 Virology Abstract HIV R3H 72 75 Env;gp120 42;51 50;56 7618287 Mutational analysis of the conserved cysteine residues in the simian immunodeficiency virus matrix protein. Substitution of alanine for cysteine 87 had little effect on particle release and Env glycoprotein association. 1995 Virology Abstract HIV C87A 16 39 Env 82 85 7626598 Kinetic characterization and cross-resistance patterns of HIV-1 protease mutants selected under drug pressure. Eleven different recombinant, drug-resistant HIV-1 protease (HIV PR) mutants--R8Q, V32I, M46I, V82A, V82F, V82I, I84V, V32I/I84V, M46I/V82F, M46I/I84V, and V32I/K45I/F53L/A71V/I84V/L89M--were generated on the basis of results of in vitro selection experiments using the inhibitors A-77003, A-84538, and KNI-272. 1995 Biochemistry Abstract HIV A71V;F53L;I84V;K45I;L89M;V32I;I84V;I84V;I84V;M46I;M46I;M46I;R8Q;V32I;V32I;V82A;V82F;V82F;V82I 171;166;176;161;181;156;124;113;146;89;130;141;78;83;119;95;101;135;107 175;170;180;165;185;160;128;117;150;93;134;145;81;87;123;99;105;139;111 PR;PR 51;65 59;67 7636964 In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. A triple protease mutant infectious clone carrying the mutations Met-46-->Ile, Ile-47-->Val, and Ile-50-->Val, however, showed much greater reduction in sensitivity (14- to 20-fold) to VB-11,328 and VX-478. 1995 Journal of virology Abstract HIV M46I 65 77 PR 9 17 7636964 In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. The mutant protease Ile-50-->Val displays a much lower affinity for the inhibitors than the parent enzyme (< or = 80-fold). 1995 Journal of virology Abstract HIV I50V 20 32 PR 11 19 7636964 In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. The protease triply mutated at Met-46-->Ile, Ile-47-->Val, and Ile-50-->Val shows an even greater decrease in inhibitor binding (< or = 270-fold). 1995 Journal of virology Abstract HIV M46I 31 43 PR 4 12 7636964 In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. This is the first observation in HIV protease resistance studies of an Ile-50-->Val mutation, a mutation that appears to arise uniquely against the sulfonamide inhibitor class. 1995 Journal of virology Abstract HIV I50V 71 83 PR 37 45 7636964 In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. When the substitutions observed were introduced as single mutations into an HIV-1 infectious clone (HXB2), only the Ile-50-->Val mutant showed reduced sensitivity (two- to threefold) to VB-11,328 and VX-478. 1995 Journal of virology Abstract HIV I50V 116 128 7636988 Analysis of resistance to human immunodeficiency virus type 1 protease inhibitors by using matched bacterial expression and proviral infection vectors. G48V, L90M, and G48V/L90M exhibited successively less processing in vitro than the wild-type enzyme, and the purified enzymes were 220-, 20-, and 720-fold, respectively, less sensitive to Ro 31-8959. 1995 Journal of virology Abstract HIV G48V;L90M;L90M;G48V 16;21;6;0 20;25;10;4 7636988 Analysis of resistance to human immunodeficiency virus type 1 protease inhibitors by using matched bacterial expression and proviral infection vectors. The reduced enzyme sensitivity correlated directly with the sensitivities of the matched recombinant viruses, in that individual mutations L90M and G48V conferred 2-fold and 4- to 6-fold increases in 50% inhibitory concentration, respectively, whereas G48V/L90M was 8 to 10 times less sensitive to Ro 31-8959. 1995 Journal of virology Abstract HIV G48V;G48V;L90M;L90M 148;252;257;139 152;256;261;143 7636988 Analysis of resistance to human immunodeficiency virus type 1 protease inhibitors by using matched bacterial expression and proviral infection vectors. The utility of this vector system was demonstrated by using protease variants glycine to valine at amino acid 48 (G48V) and leucine to methionine at amino acid 90 (L90M) identified after passage of HIV-1 in the Roche phase II clinical trial protease inhibitor Ro 31-8959 (H. 1995 Journal of virology Abstract HIV G48V;G48V;L90M;L90M 114;78;164;124 118;112;168;162 PR;PR 60;241 68;249 7665551 Three-dimensional structure of a mutant HIV-1 protease displaying cross-resistance to all protease inhibitors in clinical trials. Analysis of mutational effects in the human immunodeficiency virus type-1 (HIV-1) provirus has revealed that as few as four amino acid side-chain substitutions in the HIV-1 protease (M46I/L63P/V82T/I84V) suffice to yield viral variants cross-resistant to a panel of protease inhibitors either in or being considered for clinical trials (Condra, J. 1995 The Journal of biological chemistry Abstract HIV M46I;I84V;L63P;V82T 183;198;188;193 187;202;192;197 PR;PR 173;266 181;274 7665551 Three-dimensional structure of a mutant HIV-1 protease displaying cross-resistance to all protease inhibitors in clinical trials. In the MK639-bound form, the V82T substitution introduces an unfavorable hydrophilic moiety for binding in the active site and the I84V substitution creates a cavity (unoccupied by water) that should lead to a decrease in van der Waals contacts with the inhibitor. 1995 The Journal of biological chemistry Abstract HIV I84V;V82T 131;29 135;33 7665551 Three-dimensional structure of a mutant HIV-1 protease displaying cross-resistance to all protease inhibitors in clinical trials. The role of the M46I and L63P substitutions in drug resistance is not obvious from the crystallographic data, but they induce conformational perturbations (0.9-1.1 A) in the flap domain of the native enzyme and may affect the stability and/or activity of the enzyme unrelated directly to binding. 1995 The Journal of biological chemistry Abstract HIV L63P;M46I 25;16 29;20 7678689 Human immunodeficiency virus type 1-specific [2',5'-bis-O-(tert- butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)-purine analogues show a resistance spectrum that is different from that of the human immunodeficiency virus type 1-specific non-nucleoside analogues. The reverse transcriptase (RT) of HIV-1/TSAO-m1Hx shows a single amino acid change (138-Glu to Lys) that is identical to the amino acid change that has recently been observed in several HIV-1/TSAO-pyrimidine mutant strains. 1993 Molecular pharmacology Abstract HIV E138K 84 98 RT;RT 4;27 25;29 7678690 A single conservative amino acid substitution in the reverse transcriptase of human immunodeficiency virus-1 confers resistance to (+)-(5S)-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5, 1- jk][1,4]benzodiazepin-2(1H)-thione (TIBO R82150). DNA sequencing of cloned resistant RT, combined with site-specific mutational analyses and construction of mutant recombinant proviruses, demonstrated that a single, conservative amino acid substitution (Leu100 to Ile) in HIV-1 RT is responsible for high level R82150 resistance and partial nevirapine resistance. 1993 Molecular pharmacology Abstract HIV L100I 204 217 RT;RT 35;228 37;230 7679098 Biochemical analysis of human immunodeficiency virus-1 reverse transcriptase containing a mutation at position lysine 263. Highly purified mutant enzyme K263S bound natural dNTP substrates and primed polynucleic acid substrates with equal affinity when compared to the wild type reverse transcriptase. 1993 The Journal of biological chemistry Abstract HIV K263S 30 35 RT 156 177 7679098 Biochemical analysis of human immunodeficiency virus-1 reverse transcriptase containing a mutation at position lysine 263. We studied this interaction directly by using site-specific mutagenesis to change lysine 263 to a serine. 1993 The Journal of biological chemistry Abstract HIV K263S 82 104 7679100 Enzymatic analysis of two HIV-1 reverse transcriptase mutants with mutations in carboxyl-terminal amino acid residues conserved among retroviral ribonucleases H. The N494D mutant closely resembles the wild-type RNase H, exhibits an endonuclease activity and a processive RNase H activity, gives rise to small RNA hydrolysis products, and acts in concert with the RT. 1993 The Journal of biological chemistry Abstract HIV N494D 4 9 RT 201 203 7679100 Enzymatic analysis of two HIV-1 reverse transcriptase mutants with mutations in carboxyl-terminal amino acid residues conserved among retroviral ribonucleases H. The Q475E mutant is more defective and resembles the H539N mutant, exhibits a retarded endonuclease activity and an impaired 3'-->5' processive RNA cleavage activity, gives rise to predominantly larger RNA hydrolysis products, is less processive in the presence of competitor substrate, and is defective in its ability to hydrolyze the polypurine tract and homopolymeric hybrids. 1993 The Journal of biological chemistry Abstract HIV H539N;Q475E 53;4 58;9 7679100 Enzymatic analysis of two HIV-1 reverse transcriptase mutants with mutations in carboxyl-terminal amino acid residues conserved among retroviral ribonucleases H. They were expressed as recombinant proteins, purified, and analyzed for their in vitro properties in comparison to the p66 homodimeric wild-type and a previously described H539N mutant. 1993 The Journal of biological chemistry Abstract HIV H539N 172 177 7679100 Enzymatic analysis of two HIV-1 reverse transcriptase mutants with mutations in carboxyl-terminal amino acid residues conserved among retroviral ribonucleases H. Two amino acids highly conserved among all 14 known RT sequences but not in the bacterial RNase H have been mutagenized resulting in the mutant proteins N494D and Q475E. 1993 The Journal of biological chemistry Abstract HIV N494D;Q475E 153;163 158;168 RT 52 54 7680476 Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase. An HIV-1 strain containing the Tyr181-->Cys mutation in the reverse transcriptase region displayed reduced sensitivity. 1993 Proc Natl Acad Sci U S A Abstract HIV Y181C 31 43 RT 60 81 7682649 Kinetics of different human immunodeficiency virus type 1 reverse transcriptases resistant to human immunodeficiency virus type 1-specific reverse transcriptase inhibitors. Mutations Y181C, Y181I, and Y188L led to reduced sensitivity, albeit of varying extents, to all HIV-1-specific RT inhibitors. 1993 Molecular pharmacology Abstract HIV Y181C;Y181I;Y188L 10;17;28 15;22;33 RT 111 113 7682649 Kinetics of different human immunodeficiency virus type 1 reverse transcriptases resistant to human immunodeficiency virus type 1-specific reverse transcriptase inhibitors. The catalytic constant of the Y181I mutant was 6-fold higher and that of the Y188L mutant was 6-fold lower. 1993 Molecular pharmacology Abstract HIV Y181I;Y188L 30;77 35;82 7682649 Kinetics of different human immunodeficiency virus type 1 reverse transcriptases resistant to human immunodeficiency virus type 1-specific reverse transcriptase inhibitors. The kcat of the Y181C mutant was similar to that of the wild-type RT (18 sec-1 x 10(-3)). 1993 Molecular pharmacology Abstract HIV Y181C 16 21 RT 66 68 7682649 Kinetics of different human immunodeficiency virus type 1 reverse transcriptases resistant to human immunodeficiency virus type 1-specific reverse transcriptase inhibitors. The rapid emergence of drug-resistant escape mutants in vitro (cell culture) and in vivo (patients) is predominantly linked to the Y181C mutation. 1993 Molecular pharmacology Abstract HIV Y181C 131 136 7682649 Kinetics of different human immunodeficiency virus type 1 reverse transcriptases resistant to human immunodeficiency virus type 1-specific reverse transcriptase inhibitors. Whereas TIBO displayed a linear mixed-type (noncompetitive) inhibition with respect to the deoxynucleotide substrate when wild-type p66/p51 was used, the pattern of inhibition became competitive or uncompetitive with Y181C or Y181I, respectively. 1993 Molecular pharmacology Abstract HIV Y181C;Y181I 217;226 222;231 7683648 The interaction of illimaquinone, a selective inhibitor of the RNase H activity, with the reverse transcriptases of human immunodeficiency and murine leukemia retroviruses. The above conclusion is further supported by the fact that the RNase H activity of an enzymatically active mutant of HIV-1 RT, in which cysteine 280 was replaced by serine, was substantially more resistant to illimaquinone than the corresponding activity of the wild-type enzyme. 1993 The Journal of biological chemistry Abstract HIV C280S 136 171 RT 123 125 7683706 [Mutations of HIV-1 RT gene isolated from patients treated with AZT]. Some of the 14 clones also had other mutations at codon 67 (Asp-->Asn or Ser), codon 70 (Lys-->Arg) and codon 219 (Lys-->Glu). 1993 Kansenshogaku zasshi Abstract HIV K219E 104 125 Asp 60 63 7683725 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase. 15-18), 1 possesses improved inhibitory potency with respect to the wild-type RT, as well as the K103N and Y181C mutant enzymes. 1993 Journal of medicinal chemistry Abstract HIV K103N;Y181C 97;107 102;112 RT 78 80 7684216 Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Sequence analysis of amplified reverse transcriptase from a patient who had received (-)-BCH-189 therapy for 4 months demonstrated a mixture of the Met-184-to-Val (GTG) mutation and the parental genotype, indicating that the Met-184 mutation can occur in vivo. 1993 Antimicrobial agents and chemotherapy Abstract HIV M184V 148 162 RT 31 52 7685109 A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors. The effects of the P236L RT substitution suggest that emergence of BHAP-resistant virus in vivo could produce a viral population sensitized to inhibition by these other nonnucleoside RT inhibitors. 1993 Proc Natl Acad Sci U S A Abstract HIV P236L 19 24 RT;RT 25;183 27;185 7685109 A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors. This sensitization caused by P236L was also observed in cell culture with BHAP-resistant HIV-1. 1993 Proc Natl Acad Sci U S A Abstract HIV P236L 29 34 7685109 A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors. With both variants, HIV-1 resistance to BHAP RT inhibitors was caused by a RT mutation that results in a proline-to-leucine substitution at amino acid 236 (P236L). 1993 Proc Natl Acad Sci U S A Abstract HIV P236L;P236L 156;105 161;154 RT;RT 45;75 47;77 7685907 Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. All mutants with Met184-->Val were cross-resistant to 3TC and FTC. 1993 Proc Natl Acad Sci U S A Abstract HIV M184V 17 29 7685907 Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Interestingly, when both Met184-->Val and Tyr181-->Cys substitutions were present, highly resistant virus reverted to complete AZT sensitivity. 1993 Proc Natl Acad Sci U S A Abstract HIV M184V;Y181C 25;42 37;54 7685907 Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Similar suppression of AZT resistance was seen with Tyr181-->Cys. 1993 Proc Natl Acad Sci U S A Abstract HIV Y181C 52 64 7685907 Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. The Met184-->Val mutation did not influence nevirapine resistance, but resistance to AZT was suppressed. 1993 Proc Natl Acad Sci U S A Abstract HIV M184V 4 16 7685907 Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. When the mutation Met184-->Val was introduced into the infectious clone HXB2, this change alone accounted for the resistance (> 1000-fold) seen with both 3TC and FTC, and for a 5- to 15-fold reduction in sensitivity to their (+) enantiomers. 1993 Proc Natl Acad Sci U S A Abstract HIV M184V 18 30 7685964 HIV-1-specific reverse transcriptase inhibitors show differential activity against HIV-1 mutant strains containing different amino acid substitutions in the reverse transcriptase. As a rule, the TSAO-resistant HIV-1 strains (138 Glu-->Lys) and TIBO (R82150 or R82913)-resistant HIV-1 strains (Leu 100-->Ile or 103 Lys-->Asn) are sensitive to the other HIV-1-specific RT inhibitors, whereas the amino acid change 181 Tyr-->Cys results in a significant reduction of sensitivity to all classes of the HIV-1-specific RT inhibitors. 1993 Virology Abstract HIV E138K;K103N;L100I;Y181C 45;130;113;232 58;143;127;245 RT;RT 187;333 189;335 7685964 HIV-1-specific reverse transcriptase inhibitors show differential activity against HIV-1 mutant strains containing different amino acid substitutions in the reverse transcriptase. Four TIBO (R82913)-resistant HIV-1 strains contained different amino acid substitutions: 103 Lys-->Asn (strain 2), 100 Leu-->Ile and 138 Glu-->Lys (strain B02), 100 Leu-->Ile and 181 Tyr-->Cys (strain 1), 100 Leu-->Ile and 188 Tyr-->His (strain B22). 1993 Virology Abstract HIV E138K;K103N;L100I;L100I;L100I;Y181C;Y188H 133;89;115;161;205;179;223 146;102;128;174;218;192;236 7685964 HIV-1-specific reverse transcriptase inhibitors show differential activity against HIV-1 mutant strains containing different amino acid substitutions in the reverse transcriptase. The following amino acid substitutions were found: 138 Glu-->Lys (TSAO-T), 181 Tyr-->Cys (nevirapine), 181 Tyr-->Cys (pyridinone), and 100 Leu-->Ile (TIBO R82150). 1993 Virology Abstract HIV E138K;L100I;Y181C;Y181C 51;135;75;103 64;148;88;116 7685995 U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication. Finally, although the RT amino acid substitutions K103N (lysine 103 to asparagine) and Y181C (tyrosine 181 to cysteine), which confer cross-resistance to several nonnucleoside inhibitors, also decrease the potency of U-90152, this drug retains significant activity against these mutant RTs in vitro (IC50s, approximately 8 microgramM). 1993 Antimicrobial agents and chemotherapy Abstract HIV K103N;K103N;Y181C;Y181C 50;57;87;94 55;81;92;118 RT;RT 22;286 24;289 7686904 Fluorimetric analysis of recombinant p15 HIV-1 ribonuclease H. Recombinant p15 RNase H preparations containing mutations at position 478 (Glu478-->Gln478) or 539 (His539 -->Phe539), which are highly conserved between bacterial and retroviral RNases H, were also analyzed. 1993 The Journal of biological chemistry Abstract HIV E478Q 75 90 7687061 Mechanism of resistance of human immunodeficiency virus type 1 to 2',3'-dideoxyinosine. A molecular clone containing the wild-type reverse transcriptase (RT) coding region of human immunodeficiency virus type 1 (HIV-1) was constructed, and site-directed mutagenesis was used to introduce mutations--Leu74-->Val (L74V), T215Y, and the combination L74V/T215Y--into the RT coding region. 1993 Proc Natl Acad Sci U S A Abstract HIV L74V;L74V;L74V;T215Y;T215Y 224;258;211;231;263 228;262;222;236;268 RT;RT;RT 43;66;279 64;68;281 7688467 Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors. HIV-1 RT in which the Glu-138-->Lys substitution was introduced by site-directed mutagenesis and expressed in Escherichia coli could not be purified because of rapid degradation. 1993 Proc Natl Acad Sci U S A Abstract HIV E138K 22 35 RT 6 8 7688467 Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors. However, HIV-1 RT containing the Glu-138-->Arg substitution was stable. 1993 Proc Natl Acad Sci U S A Abstract HIV E138R 33 46 RT 15 17 7688822 Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy. In all cases the Tyr-181-->Cys mutation appeared; the virus showed markedly reduced sensitivity to all HIV-1-specific inhibitors but retained sensitivity to 2',3'-dideoxynucleoside analogs such as zidovudine, ddC, and ddI. 1993 Journal of virology Abstract HIV Y181C 17 30 7688822 Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy. Our findings argue against simultaneous combination of two different nonnucleoside RT inhibitors that are unable to inhibit HIV-1 mutant strains containing the Tyr-181-->Cys mutation when administered as single drugs. 1993 Journal of virology Abstract HIV Y181C 160 173 RT 83 85 7688822 Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy. The mutant viruses showed the following amino acid substitutions in their reverse transcriptase (RT): Leu-100-->Ile for HIV-1/BHAP; Lys-103-->Asn for HIV-1/TIBO; Val-106-->Ala for HIV-1/Nev; and Glu-138-->Lys for HIV-1/TSAO-m3T. 1993 Journal of virology Abstract HIV E138K;K103N;L100I;V106A 195;132;102;162 208;145;115;175 RT;RT 74;97 95;99 7689822 pol mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo. AZT resistance coexisted with ddI resistance following acquisition of Leu-74-->Val in three clinical isolates, indicating that the suppressive effect of Val-74 on the AZT resistance of the virus does not occur in all genetic contexts. 1993 Antimicrobial agents and chemotherapy Abstract HIV L74V 70 82 7689822 pol mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo. Changes in ddATP inhibition of RNA-dependent DNA polymerase activity fully accounted for the ddI resistance of the virus caused by a Leu-74-->Val substitution in RT, including an augmentation by the AZT-selected substitutions Thr-215-->Tyr and Lys-219-->Gln in RT. 1993 Antimicrobial agents and chemotherapy Abstract HIV L74V 133 145 Pol;RT;RT 49;162;261 59;164;263 7692302 Convergent combination therapy can select viable multidrug-resistant HIV-1 in vitro. We found no evidence for 'replication incompatible' combinations of resistance mutations, although a mutation (M184-->V) conferring oxathiolane-cytosine nucleoside resistance in reverse transcriptase completely suppressed AZT resistance in a triple-resistant background. 1993 Nature Abstract HIV M184V 111 119 RT 178 199 7693973 Immune escape by human immunodeficiency virus type 1 from neutralizing antibodies: evidence for multiple pathways. In this report we demonstrate that immune escape via a single-amino-acid substitution (A281V) within a conserved region of the envelope glycoprotein gp120 confers neutralization resistance against a broadly reactive neutralizing antiserum from a seropositive individual. 1993 Journal of virology Abstract HIV A281V 87 92 Env;gp120 127;149 135;154 7693973 Immune escape by human immunodeficiency virus type 1 from neutralizing antibodies: evidence for multiple pathways. We have previously shown that neutralization resistance of an escape mutant with an amino acid substitution in the transmembrane protein (A582T) occurs because of alteration of a conformational epitope that is recognized by neutralizing antibodies directed against the CD4 binding site. 1993 Journal of virology Abstract HIV A582T 138 143 7694068 Human immunodeficiency virus type 1 drug-resistance patterns with different 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives. When HIV-1 strains were selected for resistance against three different HEPT derivatives [i.e., HEPT and its derivatives 5-ethyl-1-ethoxymethyl-6-benzyluracil(E-EBU) and 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil (EBU-dM)], HEPT selected for the mutation 188-Tyr-->His, E-EBU for 181-Tyr-->Cys, and E-EBU-dM for 106-Val-->Ala, in the reverse transcriptase of the mutant viruses. 1993 Molecular pharmacology Abstract HIV Y188H 264 277 RT 343 364 7694651 Structure/function studies of HIV-1(1) reverse transcriptase: dimerization-defective mutant L289K. A central region of primary sequence contains a leucine hepta-repeat motif from leucine 282 to leucine 310 that has been suggested to be involved in dimerization [Baillon, J. 1993 Biochemistry Abstract HIV L282L 80 102 7694651 Structure/function studies of HIV-1(1) reverse transcriptase: dimerization-defective mutant L289K. L289K-p66 was unable to dimerize with itself and wild-type or L289K-p51. 1993 Biochemistry Abstract HIV L289K;L289K 62;0 67;5 7707502 Adaptation of human immunodeficiency virus type 1 to cells expressing a binding-deficient CD4 mutant (lysine 46 to aspartic acid). In cells expressing the wild-type CD4 glycoproteins, the same V2 and V3 residue changes also increased the efficiency of replication of a virus exhibiting decreased receptor-binding ability due to an amino acid change (aspartic acid 368 to glutamic acid) in the gp120 glycoprotein. 1995 Journal of virology Abstract HIV D368E 219 253 gp120 262 267 7707502 Adaptation of human immunodeficiency virus type 1 to cells expressing a binding-deficient CD4 mutant (lysine 46 to aspartic acid). The mutant CD4 (46 K/D) contained a single amino acid change (lysine 46 to aspartic acid) in the CDR2 loop of domain 1, which results in a 15-fold reduction in affinity for the viral gp120 glycoprotein. 1995 Journal of virology Abstract HIV K46D 62 88 gp120 183 188 7726006 Identification of an amino acid substitution involved in the reduction of sensitivity of HIV-1 to an inhibitor of viral proteinase. Substitution of glycine by valine at position 48 of the PR protein was found. 1994 Acta virologica Abstract HIV G48V 16 48 PR 56 58 7745698 Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy. All subjects had evidence of RT T215Y/F mutation in both RNA in plasma and PBMC DNA at baseline. 1995 Journal of virology Abstract HIV T215F;T215Y 32;32 39;39 RT 29 31 7745698 Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy. HIV RNA in plasma demonstrated a significantly higher RT T215Y/F mutant/WT ratio than that of PBMC viral DNA, both at baseline and after ZDV-ddI combination therapy in all subjects. 1995 Journal of virology Abstract HIV T215F;T215Y 57;57 64;64 RT 54 56 7745698 Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy. In all subjects, no significant changes in PBMC DNA viral load and RT T215Y/F or WT levels were seen. 1995 Journal of virology Abstract HIV T215F;T215Y 70;70 77;77 RT 67 69 7745698 Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy. Subjects with a mixture of WT and RT T215Y/F HIV RNA in plasma at baseline demonstrated a decline in RNA levels in plasma after the addition of ddI. 1995 Journal of virology Abstract HIV T215F;T215Y 37;37 44;44 RT 34 36 7745698 Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy. Subjects with only RT T215Y/F RNA present in plasma at baseline remained so and demonstrated no decline in RNA levels in plasma. 1995 Journal of virology Abstract HIV T215F;T215Y 22;22 29;29 RT 19 21 7745698 Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy. The relative amounts of wild-type (WT) sequence, ddI resistance-associated codon changes (reverse transcriptase [RT] gene codon 65 K-->R [RT K65R], RT 174V, RT I135K/T/V, and RT M184I/V), and ZDV resistance-associated codon change (RT T215Y/F) from HIV RNA in plasma and RT T215Y/F from PBMC viral DNA were determined by differential hybridization of PCR products from 10 of 11 subjects. 1995 Journal of virology Abstract HIV I135K;I135T;I135V;K65R;M184I;M184V;T215F;T215F;T215Y;T215Y 160;160;160;141;178;178;235;274;235;274 169;169;169;145;185;185;242;281;242;281 RT;RT;RT;RT;RT;RT;RT;RT 90;113;138;148;157;175;232;271 111;115;140;150;159;177;234;273 7745698 Determination of human immunodeficiency virus RNA in plasma and cellular viral DNA genotypic zidovudine resistance and viral load during zidovudine-didanosine combination therapy. This study suggests that determination of relative amounts of RT T215Y/F and WT species from HIV RNA in plasma at baseline may be predictive of virologic response during ZDV-ddI combination therapy. 1995 Journal of virology Abstract HIV T215F;T215Y 65;65 72;72 RT 62 64 7751690 Human immunodeficiency virus type 1 (HIV-1) viremia changes and development of drug-related mutations in patients with symptomatic HIV-1 infection receiving alternating or simultaneous zidovudine and didanosine therapy. Analyses with nested polymerase chain reaction revealed that the emergence of the didanosine-related position 74 Leu-->Val mutation was significantly blocked in both regimens, while the zidovudine-related mutation at codon 215 was not affected. 1995 The Journal of infectious diseases Abstract HIV L74V 110 122 Pol 21 31 7773792 Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase. Modelling studies predicted that the V82A mutation would result in decreased van der Waals' interactions with the phenyl rings of A-77003 in both S1 and S1' subsites. 1995 Nature structural biology Abstract HIV V82A 37 41 7773792 Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase. We report an analysis of the structure of a Val 82 to Ala mutant of HIV-1 proteinase complexed to A-77003, a C2 symmetry-based inhibitor. 1995 Nature structural biology Abstract HIV V82A 44 57 7796268 Flap opening in HIV-1 protease simulated by 'activated' molecular dynamics. In contrast, similar molecular dynamics simulations on the M46I mutant, which is associated with drug resistance, indicates that this mutation stabilizes the flaps in a closed conformation. 1995 Nature structural biology Abstract HIV M46I 59 63 7815532 Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor. Molecular characterization of the variants shows that an isoleucine-to-valine substitution at position 84 results in a substantial decrease in sensitivity to the drug. 1995 Journal of virology Abstract HIV I84V 57 105 7827064 Effect of point mutations on the kinetics and the inhibition of human immunodeficiency virus type 1 protease: relationship to drug resistance. In these mutants, Val82 was substituted separately by Asn, Glu, Ala, Ser, Asp, and Gln; Asp30 was individually substituted by Phe or Trp; Gly48 by His, Asp, and Tyr, respectively; and Lys45 by Glu. 1995 Biochemistry Abstract HIV K45E 184 196 Asp;Asp;Asp 74;88;152 77;91;155 7831807 Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959. Sequence comparison to wild-type (wt) proteinase demonstrated two amino acid substitutions in the resistant virus, a Gly to Val exchange at position 48 and a Leu to Met exchange at position 90. 1995 Virology Abstract HIV G48V;L90M 117;158 151;192 7853517 The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity. In addition, the P31L mutant did not contain detectable amounts of reverse transcriptase and had an immature core morphology, as determined by electron microscopy. 1995 Journal of virology Abstract HIV P31L 17 21 RT 67 88 7853517 The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity. Mutations that probably alter the structure of NCp7 structure led to the formation of very poorly infectious virus (A30P) or noninfectious virus (P31L and R32G). 1995 Journal of virology Abstract HIV A30P;P31L;R32G 116;146;155 120;151;159 NC 47 49 7853517 The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity. R29S had a wild-type phenotype, and the replacement of 32RKK34 by SSS (S3 mutant) resulted in a decrease by no more than 100-fold of the virus titer. 1995 Journal of virology Abstract HIV R29S 0 4 7884862 Characterization of a human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor. Further genotypic analysis of the protease genes from earlier passages of virus indicated that the A71T mutation emerged prior to the V82A change. 1995 Journal of virology Abstract HIV A71T;V82A 99;134 103;138 PR 34 42 7884862 Characterization of a human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor. Genetic analysis of the protease gene from a drug-resistant variant revealed an Ala-to-Thr change at amino acid residue 71 (A71T) and a Val-to-Ala change at residue 82 (V82A). 1995 Journal of virology Abstract HIV A71T;A71T;V82A;V82A 124;80;169;136 128;122;173;167 PR 24 32 7884862 Characterization of a human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor. Subsequent drug sensitivity assays on the mutant proteases and viruses indicated that the V82A substitution was responsible for most of the resistance observed. 1995 Journal of virology Abstract HIV V82A 90 94 PR 49 58 7884862 Characterization of a human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor. To determine the effects of these mutations on protease and virus drug susceptibility, recombinant protease and proviral HIV type 1 clones containing the single mutations A71T and V82A or double mutation A71T/V82A were constructed. 1995 Journal of virology Abstract HIV A71T;A71T;V82A;V82A 171;204;209;180 175;208;213;184 PR;PR 47;99 55;107 7886951 A side chain at position 48 of the human immunodeficiency virus type-1 protease flap provides an additional specificity determinant. Substitution of glycine with glutamic acid at position 48 of the human immunodeficiency virus protease resulted in an enzyme with reduced activity on one of the protease processing sites in the viral Pol polyprotein precursor. 1995 Virology Abstract HIV G48E 16 57 PR;PR;Pol 94;161;200 102;169;203 7904656 Increase in soluble CD4 binding to and CD4-induced dissociation of gp120 from virions correlates with infectivity of human immunodeficiency virus type 1. A single amino acid substitution in part of the CD4 binding site of gp120 (Gly-427 to Arg) enhanced both spontaneous and CD4-induced shedding of gp120 from virions, while a single change in the fusogenic region of gp41 (Met-7 to Val) affected only CD4-induced shedding. 1994 Journal of virology Abstract HIV G427R;M7V 75;220 89;232 gp120;gp120;gp41 68;145;214 73;150;218 7918387 1H NMR structure and biological studies of the His23-->Cys mutant nucleocapsid protein of HIV-1 indicate that the conformation of the first zinc finger is critical for virus infectivity. In order to more precisely elucidate the structural role of the zinc finger motif, His23 was replaced by Cys in the proximal finger of the peptide (13-64)NCp7 which retains NCp7 activities in vitro. 1994 Biochemistry Abstract HIV H23C 83 108 NC;NC 154;173 156;175 7983762 Identification and characterization of a temperature-sensitive mutant of human immunodeficiency virus type 1 by alanine scanning mutagenesis of the integrase gene. However, during infection at the nonpermissive temperature of 39.5 degrees C, K136A/E138A is capable of only one round of integration. 1995 Journal of virology Abstract HIV E138A;K136A 84;78 89;83 7983762 Identification and characterization of a temperature-sensitive mutant of human immunodeficiency virus type 1 by alanine scanning mutagenesis of the integrase gene. In the ts mutant virus, the lysine at amino acid 136 and the glutamic acid at amino acid 138 of integrase have been replaced with alanines (K136A/E138A). 1995 Journal of virology Abstract HIV K136A;E138A 140;146 145;151 IN 96 105 7983762 Identification and characterization of a temperature-sensitive mutant of human immunodeficiency virus type 1 by alanine scanning mutagenesis of the integrase gene. It is the temperature at which the K136A/E138A virion is synthesized, not the temperature at which infection occurs, which determines the ability of the virus to integrate. 1995 Journal of virology Abstract HIV E138A;K136A 41;35 46;40 7983762 Identification and characterization of a temperature-sensitive mutant of human immunodeficiency virus type 1 by alanine scanning mutagenesis of the integrase gene. We demonstrate that the defect responsible for the ts phenotype of K136A/E138A is localized to a step after proviral formation and integrase protein synthesis but prior to particle maturation. 1995 Journal of virology Abstract HIV E138A;K136A 73;67 78;72 IN 131 140 7983762 Identification and characterization of a temperature-sensitive mutant of human immunodeficiency virus type 1 by alanine scanning mutagenesis of the integrase gene. When K136A/E138A is synthesized at 35 degrees C, it replicates to a similar degree as wild-type virus during infection of CEM cells at 35 degrees C on the basis of syncytium formation, levels of core antigen, and reverse transcriptase activity. 1995 Journal of virology Abstract HIV E138A;K136A 11;5 16;10 RT 213 234 8035491 Role of the major homology region of human immunodeficiency virus type 1 in virion morphogenesis. By contrast, the substitution of arginine 167 with alanine had only a two- to threefold effect on particle yield but led to the formation of aberrant core structures. 1994 Journal of virology Abstract HIV R167A 33 58 8035491 Role of the major homology region of human immunodeficiency virus type 1 in virion morphogenesis. The replacement of tyrosine 164 with alanine substantially impaired viral particle production. 1994 Journal of virology Abstract HIV Y164A 19 44 8068616 The HIV-1 protease as enzyme and substrate: mutagenesis of autolysis sites and generation of a stable mutant with retained kinetic properties. However, one of the mutant proteases, Q7K/L33I/L63I, was highly resistant to autolysis, while retaining the physical properties, specificity, and susceptibility to inhibition of the wild-type enzyme. 1994 Biochemistry Abstract HIV L33I;L63I;Q7K 42;47;38 46;51;41 PR 27 36 8068616 The HIV-1 protease as enzyme and substrate: mutagenesis of autolysis sites and generation of a stable mutant with retained kinetic properties. Q7K/L33I/L63I should find useful application as a stable surrogate of the HIV-1 protease. 1994 Biochemistry Abstract HIV L33I;L63I;Q7K 4;9;0 8;13;3 PR 80 88 8107101 The human immunodeficiency virus type 1 encoded Vpu protein is phosphorylated by casein kinase-2 (CK-2) at positions Ser52 and Ser56 within a predicted alpha-helix-turn-alpha-helix-motif. In addition, we studied phosphorylation of Vpu by endogenous CK-2 following in vitro translation in rabbit reticulocyte lysate of wild-type Vpu or a mutant, Vpum2/6, carrying serine to asparagine changes at amino acid positions 52 and 56. 1994 Journal of molecular biology Abstract HIV S52N 175 230 Vpu;Vpu;Vpu 43;140;157 46;143;160 8107101 The human immunodeficiency virus type 1 encoded Vpu protein is phosphorylated by casein kinase-2 (CK-2) at positions Ser52 and Ser56 within a predicted alpha-helix-turn-alpha-helix-motif. The two CK-2 phosphorylation sites are conserved in all known Vpu sequences and represent the consensus Ser52GlyAsn(Glu/Asp)Ser(Glu/Asp)Gly(Glu/Asp)59. 1994 Journal of molecular biology Abstract HIV S52G;S52N 104;104 115;115 Vpu;Asp;Asp;Asp 62;120;132;144 65;123;135;147 8110758 Proteolytic processing mechanisms of a miniprecursor of the aspartic protease of human immunodeficiency virus type 1. The expression in Escherichia coli and the isolation of a 14-kDa HIV-1 PR "miniprecursor" with Ala28 mutated to serine has permitted study of the mechanism for cleavage at the N-terminus of the protease. 1994 Biochemistry Abstract HIV A28S 95 118 PR;PR 194;71 202;73 8144659 In vitro characterization of nonpeptide irreversible inhibitors of HIV proteases. Comparison of the profiles of inactivation of wild-type HIV-1 protease, HIV-1 PR C95M, and HIV-1 PR C67L as well as HIV-2 protease (which has no cysteine residues) reveals the contribution of Cys-95 to the reactivity of these irreversible inhibitors. 1994 The Journal of biological chemistry Abstract HIV C67L;C95M 100;81 104;85 PR;PR;PR;PR 62;122;78;97 70;130;80;99 8144659 In vitro characterization of nonpeptide irreversible inhibitors of HIV proteases. In contrast, a mutant HIV-1 protease, HIV-1 PR C95M, in which Cys-95 has been replaced by Met, is labeled 50% less than HIV-1 protease and is fully protected by EPNP and U-85548. 1994 The Journal of biological chemistry Abstract HIV C95M 47 51 PR;PR;PR 28;126;44 36;134;46 8157644 Mutational analysis of the substrate binding pockets of the Rous sarcoma virus and human immunodeficiency virus-1 proteases. Substituting I42D, M73V, and A100L produced enzymes with lower activity, whereas a mutant that included both M73V and A100L was as active as wild type. 1994 The Journal of biological chemistry Abstract HIV A100L;A100L;I42D;M73V;M73V 29;118;13;19;109 34;123;17;23;113 8157644 Mutational analysis of the substrate binding pockets of the Rous sarcoma virus and human immunodeficiency virus-1 proteases. Substituting threonine for valine 104 (V104T), S107N, I44V, Q63M or deletion of residues 61-63 produced enzymes that were 2.5-7-fold more active than the wild type RSV PR. 1994 The Journal of biological chemistry Abstract HIV I44V;Q63M;S107N;V104T;V104T 54;60;47;39;13 58;64;52;44;37 PR 168 170 8157644 Mutational analysis of the substrate binding pockets of the Rous sarcoma virus and human immunodeficiency virus-1 proteases. These include I42D and I44V, which contribute to the S2 and S2' subsites. 1994 The Journal of biological chemistry Abstract HIV I42D;I44V 14;23 18;27 8158034 Apparent selection against transmission of zidovudine-resistant human immunodeficiency virus type 1 variants. Two of these patients had a single mutation (Thr215-->Tyr), and 2 had a double mutation (Met41-->Leu and Thr215-->Tyr) that previously has been shown to confer zidovudine resistance. 1994 The Journal of infectious diseases Abstract HIV M41L;T215T;T215T 89;45;105 101;57;117 8254733 Generation and characterization of a human immunodeficiency virus type 1 (HIV-1) mutant resistant to an HIV-1 protease inhibitor. An HIV-1 infectious DNA clone with the I-84-->V mutation also showed reduced sensitivity to this protease inhibitor. 1994 Journal of virology Abstract HIV I84V 39 47 PR 97 105 8254733 Generation and characterization of a human immunodeficiency virus type 1 (HIV-1) mutant resistant to an HIV-1 protease inhibitor. One point mutation (A-->G) at site 2082 of the pol gene that resulted in one amino acid change at site 84 of the protease from isoleucine to valine (I-84-->V) could be detected in the resistant variant. 1994 Journal of virology Abstract HIV I84V 149 157 PR;Pol 113;47 121;50 8301126 Analysis of mutant HLA-A2 molecules. Differential effects on peptide binding and CTL recognition. Most of the mutations resulted in intermediate deleterious effects on binding, with the B pocket mutant F9Y having the most dramatic negative effect on binding for both peptides. 1994 Journal of immunology (Baltimore, Md. Abstract HIV F9Y 104 107 8301126 Analysis of mutant HLA-A2 molecules. Differential effects on peptide binding and CTL recognition. Two of the mutations significantly enhanced binding of both peptides and a peptide-specific effect on binding was seen with the substitution, Y99H, which enhanced binding of the matrix peptide yet diminished binding of the pol peptide. 1994 Journal of immunology (Baltimore, Md. Abstract HIV Y99H 142 146 Matrix;Pol 178;223 184;226 8317093 Evidence for the cooperation of gp120 amino acids 322 and 448 in SIVmac entry. Analysis of site-specific mutants demonstrated that the mutation of V-->I at position 322 can indeed compensate for the 448V-->G mutation, resulting in efficient virus entry and replication by the double mutant. 1993 Virology Abstract HIV V448G 120 128 8317093 Evidence for the cooperation of gp120 amino acids 322 and 448 in SIVmac entry. Envelope glycoprotein with the 448V-->G mutation bound to soluble CD4 in a manner similar to wild type in an in vitro assay and was also translated, processed, and cleaved in a manner similar to wild-type envelope protein. 1993 Virology Abstract HIV V448G 31 39 Env;Env 0;205 8;213 8317093 Evidence for the cooperation of gp120 amino acids 322 and 448 in SIVmac entry. Sequencing of viral DNA from cultures infected with this variant revealed that the original 448V-->G mutation was retained in eight of eight clones analyzed but that six of eight clones analyzed had an additional mutation of V-->I at amino acid 322 of gp120. 1993 Virology Abstract HIV V448G 92 100 gp120 252 257 8317093 Evidence for the cooperation of gp120 amino acids 322 and 448 in SIVmac entry. The substitution of glycine for valine at amino acid 448 in the C4 domain of SIVmac239 envelope glycoprotein gp120 resulted in little or no viral infectivity for CEMX174 cells and rhesus monkey peripheral blood mononuclear cells. 1993 Virology Abstract HIV V448G 20 56 Env;gp120 87;109 95;114 8317093 Evidence for the cooperation of gp120 amino acids 322 and 448 in SIVmac entry. When CEMx174 cells were transfected with 448V-->G mutant proviral DNA and held for longer than 40 days, a variant appeared in one culture that was able to replicate with near wild-type kinetics. 1993 Virology Abstract HIV V448G 41 49 8356803 An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site. An immune-selected point-mutation (HXB2-Env:Ala582(-->Thr)) in the transmembrane protein, gp41, of the human immunodeficiency virus type 1 confers relative insensitivity to neutralization by a number of sera from HIV-1-positive persons. 1993 Virology Abstract HIV A582T 44 58 gp41;Env 90;40 94;43 8356803 An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site. Furthermore, the ability of 10 human HIV-1-positive sera to block the binding of soluble CD4 to mammalian-recombinant gp120 correlated weakly with their differentiation of neutralization between the wild-type and the Env:Ala582(-->Thr)-mutant virus. 1993 Virology Abstract HIV A582T 221 235 gp120;Env 118;217 123;220 8408067 Crystal structures of ribonuclease HI active site mutants from Escherichia coli. coli RNase HI, three mutant proteins, which were completely inactivated by the replacements of three functional residues, Asp10 by Asn (D10N), Glu48 by Gln (E48Q), and Asp70 by Asn (D70N), were crystallized. 1993 The Journal of biological chemistry Abstract HIV D10N;D10N;D70N;D70N;E48Q;E48Q 136;122;182;168;157;143 140;134;186;180;161;155 Asp;Asp 122;168 125;171 8420982 Site-directed mutagenesis of HIV-1 integrase demonstrates differential effects on integrase functions in vitro. Arg-199-->Cys delta, which lacks part of the carboxyl terminus of IN, has impaired strand transfer activity without loss of disintegration activity. 1993 The Journal of biological chemistry Abstract HIV R199C 0 13 IN 66 68 8420982 Site-directed mutagenesis of HIV-1 integrase demonstrates differential effects on integrase functions in vitro. Asp-64-->Val has no demonstrable strand transfer or disintegration activity yet maintains 3' processing activity at a diminished level. 1993 The Journal of biological chemistry Abstract HIV D64V 0 12 Asp 0 3 8466899 Inhibitor binding to the Phe53Trp mutant of HIV-1 protease promotes conformational changes detectable by spectrofluorometry. Investigation of the kinetics of the F53W protease-inhibitor binding by stopped-flow spectrofluorometry revealed a rapid increase in protein fluorescence upon formation of the enzyme-inhibitor complex. 1993 Biochemistry Abstract HIV F53W 37 41 PR 42 50 8466899 Inhibitor binding to the Phe53Trp mutant of HIV-1 protease promotes conformational changes detectable by spectrofluorometry. The Phe53Trp (F53W) mutant of HIV-1 protease was expressed in Escherichia coli and purified from bacterial lysates. 1993 Biochemistry Abstract HIV F53W;F53W 4;14 12;18 PR 36 44 8466899 Inhibitor binding to the Phe53Trp mutant of HIV-1 protease promotes conformational changes detectable by spectrofluorometry. While binding of a potent peptide-analogue inhibitor (Ki = 9 nM) to the wild-type enzyme led to no change in protein fluorescence, a 5-8% increase in fluorescence was observed with the F53W mutant, indicating an enhancement of the Trp fluorescence due to flap movement upon inhibitor binding. 1993 Biochemistry Abstract HIV F53W 185 189 8474175 Assembly-defective point mutants of the human immunodeficiency virus type 1 Gag precursor phenotypically expressed in recombinant baculovirus-infected cells. (ii) The two mutations showed different phenotypes when placed in the N-myristylated context, of which only the L268P mutation abolished extracellular budding and release of Gag particles at the plasma membrane. 1993 Journal of virology Abstract HIV L268P 112 117 Gag 174 177 8474175 Assembly-defective point mutants of the human immunodeficiency virus type 1 Gag precursor phenotypically expressed in recombinant baculovirus-infected cells. Both L268P and L322S mutants had a trans-dominant negative effect on the intracellular assembly of a non-N-myristylated, full-length (Pr55) Gag precursor expressed by a coinfecting recombinant. 1993 Journal of virology Abstract HIV L268P;L322S 5;15 10;20 Gag;PR 140;134 143;136 8474175 Assembly-defective point mutants of the human immunodeficiency virus type 1 Gag precursor phenotypically expressed in recombinant baculovirus-infected cells. The mutations consisted of nonconservative changes involving highly conserved hydrophobic residues in the p24 domain, Leu to Pro at position 268 (L268P) and Leu to Ser at amino acid 322 (L322S). 1993 Journal of virology Abstract HIV L268P;L268P;L322S;L322S 146;118;187;157 151;144;192;185 p24 106 109 8505318 Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions. Conversely, a mutation in HIV-2 protease which changed Lys7 to Gln rendered the protein 3-fold less stable and shifted the position of the initial autoproteolytic cleavage from Phe3-Ser4 to Leu5-Trp6. 1993 The Journal of biological chemistry Abstract HIV K7Q 55 66 PR 32 40 8505318 Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions. From predictions based on known substrates it was concluded that amino acids Lys or Ser in place of Gln at position 7 would prevent cleavage at the Leu5-Trp6 peptide bond, therefore stabilizing the protein. 1993 The Journal of biological chemistry Abstract HIV Q7S 84 117 8523579 Single amino acid substitution in constant region 1 or 4 of gp120 causes the phenotype of a human immunodeficiency virus type 1 variant with mutations in hypervariable regions 1 and 2 to revert. Isolation and genetic characterization of a revertant of this mutant revealed an isoleucine-for-valine substitution at position 84 in constant region 1 and an isoleucine-for-methionine substitution at position 434 in constant region 4. 1996 Journal of virology Abstract HIV M434I;V84I 159;81 213;130 8528137 Human immunodeficiency virus type 1 integrase stabilizes a linearized HIV-1 LTR plasmid in vivo. Integrase point mutations P109S and D116N drastically reduced stabilization whereas T115A and D64A had little or no effect. 1995 Biochemistry and molecular biology international Abstract HIV D116N;D64A;P109S;T115A 36;94;26;84 41;98;31;89 IN 0 9 8528729 Recombinant human immunodeficiency virus type 1 reverse transcriptase is heterogeneous. However, whereas the kinetic constants for dTTP and AZTTP for both T215Y B and T215Y C were similar to those of wt protein, T215Y A exhibited a twofold increase in Km value for dTTP and a 13-fold increase in Ki value for AZTTP with respect to wt protein purified in the same manner. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV T215Y;T215Y;T215Y 67;79;124 72;84;129 8528729 Recombinant human immunodeficiency virus type 1 reverse transcriptase is heterogeneous. Recombinant wild type (wt) and T215Y HIV-1 reverse transcriptase (RT) were isolated using three methods designated A, B, and C. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV T215Y 31 36 RT;RT 43;66 64;68 8528729 Recombinant human immunodeficiency virus type 1 reverse transcriptase is heterogeneous. The Cm values for T215Y RT did not differ from those of the respective wt; however, differences in Cm values were noted depending on how the protein was isolated. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV T215Y 18 23 RT 24 26 8528729 Recombinant human immunodeficiency virus type 1 reverse transcriptase is heterogeneous. We therefore used denaturation as detected by changes in enzyme activity to compare the conformational stability of the three samples of wt and T215Y RT A, B, and C. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV T215Y 144 149 RT 150 152 8540705 Antiviral, metabolic, and pharmacokinetic properties of the isomeric dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol. The reverse transcriptase-coding region of the mutant virus contained a single base change resulting in a change at codon 184 from Met to Val. 1995 Antimicrobial agents and chemotherapy Abstract HIV M184V 122 141 RT 4 25 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. Both the C108G VH and VK genes showed evidence of somatic mutation and antigen selection that apparently occurred in vivo during chronic exposure to HIV-1 and its antigens. 1995 Molecular immunology Abstract HIV C108G 9 14 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. In addition, the JK minigene was used in C108G VK, JK2, is apparently over-represented in anti-HIV-1 mAbs/Fabs; this minigene was used in 61% of the anti-gp120 human Fabs recently described and in three other anti-CD4-binding site human mAbs derived by EBV transformation. 1995 Molecular immunology Abstract HIV C108G 41 46 gp120 154 159 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. Nucleotide and amino acid sequence analyses reveal that C108G VH is most homologous to the human VH3 germline gene, hsigdp33 or V3-43, and the human JH4 minigene. 1995 Molecular immunology Abstract HIV C108G 56 61 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. Perhaps the most significant finding of this study is that the expressed VH and VK genes of chimpanzee mAb C108G are no more divergent from their most homologous human germline genes than are the expressed V genes of several recently characterized human anti-HIV-1 mAbs/Fabs from their apparent human germline genes. 1995 Molecular immunology Abstract HIV C108G 107 112 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. Results show that C108G expresses members of the VH3 and VK1 families, the largest VH and VK families in humans, respectively. 1995 Molecular immunology Abstract HIV C108G 18 23 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. Surprisingly, this somatic mutation was most profound in the CDR3 region of C108G VK; this region shared only 48% nucleotide homology with hsigk1012 contrasted with a homology of 94% over the remainder of these two V gene sequences. 1995 Molecular immunology Abstract HIV C108G 76 81 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. The human germline VK1 gene that is most homologous to C108G VK, hsigk1012, was previously observed in unmutated form in a human autoantibody with anti-i red blood cell antigen specificity and in seven human Fabs and a mAb directed against epitopes overlapping the CD4-binding site of HIV-1 gp120. 1995 Molecular immunology Abstract HIV C108G 55 60 gp120 291 296 8544858 Characterization of the variable regions of a chimpanzee monoclonal antibody with potent neutralizing activity against HIV-1. The variable (V) regions of C108G, a potent neutralizing chimpanzee mAb against a glycan-dependent epitope in the V2 region of HIV-1 gp120, have been characterized for reactivity with human VH and VK family-specific antisera, and their nucleotide sequences have been determined and analysed. 1995 Molecular immunology Abstract HIV C108G 28 33 gp120 133 138 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. However, the Y181C mutation weakens the nucleotide affinity 2-3-fold relative to the wild-type complex. 1996 Biochemistry Abstract HIV Y181C 13 18 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. The decreased affinity of Nevirapine for the mutant enzyme is a consequence of a faster inhibitor dissociation rate from the enzyme complex of Y181C relative to that of the wild-type. 1996 Biochemistry Abstract HIV Y181C 143 148 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. The E.DNA complex of Y181C may be saturated with Nevirapine, and the I.E.DNA complex is capable of a maximum incorporation rate of 0.1 s-1 (a 10-fold faster rate than that of the wild-type I.E.DNA complex). 1996 Biochemistry Abstract HIV Y181C 21 26 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. The overall two-step binding of nucleotide to Y181C in the presence of Nevirapine remains unaffected. 1996 Biochemistry Abstract HIV Y181C 46 51 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. The parameters governing the polymerization mechanism of reverse transcriptase containing the tyrosine to cysteine mutation at position 181 (Y181C) were determined using pre-steady-state techniques. 1996 Biochemistry Abstract HIV Y181C;Y181C 141;94 146;139 RT 57 78 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. The pathway for single nucleotide incorporation catalyzed by Y181C is similar to that determined for wild-type RT where a rate-limiting conformational change precedes fast chemistry and is followed by slow steady-state release of the primer/template. 1996 Biochemistry Abstract HIV Y181C 61 66 RT 111 113 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. The Y181C mutant enzyme binds a 25/45-mer duplex DNA tightly with a Kd of 11 nM. 1996 Biochemistry Abstract HIV Y181C 4 9 8547241 HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. We also determined the parameters governing the mechanism of nonnucleoside inhibitor resistance with Y181C. 1996 Biochemistry Abstract HIV Y181C 101 106 8551567 Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. Multidrug-resistant human immunodeficiency virus type 1 (HIV-1) strains with reverse transcriptase (RT) mutations at codons A62-->V, V75-->I, F77-->L, F116-->Y, and Q151-->M have been reported in patients receiving combination therapy with zidovudine (AZT) and didanosine (ddI). 1996 Journal of virology Abstract HIV A62V;F116Y;F77L;Q151M;V75I 124;151;142;165;133 131;159;149;173;140 RT;RT 77;100 98;102 8551567 Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. Mutation Q151-->M conferred partial resistance to AZT, ddI, zalcitibine, and stavudine, whereas a combination of four mutations conferred increased resistance to AZT, ddI, zalcitibine, and stavudine. 1996 Journal of virology Abstract HIV Q151M 9 17 8551567 Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. Replication experiments showed that clones with mutation F77-->L but without V75-->I (HIV-1(77), HIV-1(77,151), and HIV-1(77,116,151) had attenuated growth compared with that of the original HIV-1NL4-3 strain and strains containing mutations at both positions 75 and 77 (HIV-1(75,77,151) and HIV-1(75,77,116,15)). 1996 Journal of virology Abstract HIV F77L;V75I 57;77 64;84 8551608 Human immunodeficiency virus type 1 integrase mutants retain in vitro integrase activity yet fail to integrate viral DNA efficiently during infection. Mutations in the zinc binding region (H12C, H16V, and H16C), S81R, and a deletion of residues 32 through 275 yield noninfectious particles that synthesize little or no viral DNA following infection, despite wild-type levels of reverse transcriptase activity and viral RNA in the particles. 1996 Journal of virology Abstract HIV H12C;H16C;H16V;S81R 38;54;44;61 42;58;48;65 RT 227 248 8552634 Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. After continued exposure to the drug, mutations at positions so far known to be specific for resistance against nucleoside RT inhibitors (NRTIs) (L74-->V/I and V75-->L/I) were consistently detected in all cultures. 1996 Proc Natl Acad Sci U S A Abstract HIV L74V;V75L 146;160 157;169 NRTI;RT 138;123 143;125 8552634 Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. In one variant, a new mutant (G190-->Q) most likely evolved from preexisting G190-->E mutants. 1996 Proc Natl Acad Sci U S A Abstract HIV G190E;G190Q 77;30 85;38 8552634 Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. The inhibitory activities of the cellular conversion product of 2',3'-dideoxyinosine (ddI, didanosine), 2',3'-dideoxyadenosine (ddA) and of 2',3'-didehydro-3'-deoxythymidine (d4T, stavudine) against these late-passage viruses were shown to be enhanced with the L74-->V/I RT mutant virus as compared with the wild-type (wt) HIV-1MN isolate. 1996 Proc Natl Acad Sci U S A Abstract HIV L74V 261 270 RT 271 273 8552634 Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. The negative charge introduced by the G190-->E substitution was maintained at that site of the pocket by simultaneous selection for V179-->D together with G190-->Q. 1996 Proc Natl Acad Sci U S A Abstract HIV G190E;G190Q;V179D 38;155;132 46;163;140 8552634 Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. The viruses first developed mutations affecting the NNRTI-binding pocket, and five of six strains displayed the RT G190-->E substitution, which is characteristic for HIV-1 resistance against quinoxalines. 1996 Proc Natl Acad Sci U S A Abstract HIV G190E 115 123 NNRTI;RT 52;112 57;114 8558446 Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor. Comparison with the wild-type RT sequence revealed an amino acid change at position 181 (Tyr to Cys). 1996 The Journal of pharmacology and experimental therapeutics Abstract HIV Y181C 84 100 RT 30 32 8568316 Recognition of the highly conserved YMDD region in the human immunodeficiency virus type 1 reverse transcriptase by HLA-A2-restricted cytotoxic T lymphocytes from an asymptomatic long-term nonprogressor. The drug resistance mutation at RT amino acid 184 (M184V), associated with (-)-2'-deoxy-3'-thiacytidine (lamivudine), (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC), and dideoxyinosine resistance, is located within this epitope and abolishes recognition by an established CTL response. 1996 The Journal of infectious diseases Abstract HIV M184V 51 56 RT 32 34 8585767 Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (--)-2',3'-dideoxy-3'-thiacytidine. All HIV-1 strains with the Met184-->Val substitution were profoundly less susceptible to 3TC (1800- to 5500-fold decreased sensitivity) as compared to pretherapy virus strains. 1995 Antiviral research Abstract HIV M184V 27 39 8585767 Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (--)-2',3'-dideoxy-3'-thiacytidine. Genotypic analysis of HIV-1 strains isolated from 6 patients receiving 3TC revealed that as early as 2 months of therapy, HIV-1 developed a Met to Val amino acid substitution at codon 184 (Met184-->Val) in the reverse transcriptase-coding region of the pol gene. 1995 Antiviral research Abstract HIV M184V;M184V 140;189 187;201 RT;Pol 210;253 231;256 8585767 Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (--)-2',3'-dideoxy-3'-thiacytidine. Our data suggest that reversal of such beneficial changes is associated with the Met184-->Val substitution of the pol gene of HIV-1. 1995 Antiviral research Abstract HIV M184V 81 93 Pol 114 117 8590019 Structure of HIV-1 protease with KNI-272, a tight-binding transition-state analog containing allophenylnorstatine. RESULTS: The three-dimensional crystal structure of KNI-272 bound to HIV PR has been determined to 2.0 A resolution and used to analyze structure-activity data and drug resistance for the Arg8-->Gln and ILe84-->Val mutations in HIV PR. 1995 Structure (London, England Abstract HIV R8Q 188 198 PR;PR 73;232 75;234 8593008 Structure-activity and cross-resistance evaluations of a series of human immunodeficiency virus type-1-specific compounds related to oxathiin carboxanilide. A resistant virus isolate containing both Y181C combination with calanolide A, an NNRTI which retains activity against virus with the single Y181C mutation, UC10 rapidly selected a virus isolate with the K103N mutation. 1995 Antimicrobial agents and chemotherapy Abstract HIV K103N;Y181C;Y181C 204;42;141 209;47;146 NNRTI 82 87 8593008 Structure-activity and cross-resistance evaluations of a series of human immunodeficiency virus type-1-specific compounds related to oxathiin carboxanilide. The results with isolates selected in cell culture indicate that the carboxanilide compounds interact with the RT at two vulnerable sites, selecting UC-resistant virus isolates with the Y-to-C mutation at position 181 (Y181C) or the L100I substitution. 1995 Antimicrobial agents and chemotherapy Abstract HIV L100I;Y181C 233;219 238;224 RT 111 113 8619578 Preclinical evaluation of HBY 097, a new nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 replication. An HIV-1MN variant resistant to inhibition by HBY 097 displayed in the reverse transcriptase gene a mutation causing a substitution at position 190 of a glutamic acid for a glycine residue (G190 --> E), which is characteristic for quinoxaline derivatives. 1995 Antimicrobial agents and chemotherapy Abstract HIV G190E 190 200 RT 71 92 8621402 Conformational stability and catalytic activity of HIV-1 protease are both enhanced at high salt concentration. The structural basis of this effect has been explored by several independent methods by using both the wild-type enzyme and its triple mutant (Q7K/L33I/L63I) (Mildner, A. 1996 The Journal of biological chemistry Abstract HIV L33I;L63I;Q7K 147;152;143 151;156;146 8622638 Marked inhibitory activity of non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus type 1 when combined with (-)2',3'-dideoxy-3'-thiacytidine. When used individually, the compounds led to the emergence of HIV-1 strains containing the following mutations in the RT: Glu138 to lysine for TSAO-m3T, Met184 to valine for 3TC, Lys103 to threonine/asparagine for the thiocarboxanilides, and Tyr181 to cysteine for BHAP and MKC-442. 1996 Molecular pharmacology Abstract HIV E138K;M184V;Y181C 122;153;242 138;169;260 RT 118 120 8624762 Evolution of zidovudine resistance-associated genotypes in human immunodeficiency virus type 1-infected patients. In p87, K70R also appeared at 4 months, but T215Y and K219Q were not observed until 18 months and M41L not at all. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV K219Q;K70R;M41L;T215Y 54;8;98;44 59;12;102;49 8624762 Evolution of zidovudine resistance-associated genotypes in human immunodeficiency virus type 1-infected patients. In patient p74, K70R appeared after 4 months, T215Y at 5.5 months, and M41L at 13 months. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV K70R;M41L;T215Y 16;71;46 20;75;51 8624762 Evolution of zidovudine resistance-associated genotypes in human immunodeficiency virus type 1-infected patients. The evolution of the viral population in that patient was dominated by the unique appearance of T215Y and subsequently M41L, with all sequences from the last time point being descended by a single path from the pretreatment samples. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV M41L;T215Y 119;96 123;101 8631811 A soluble active mutant of HIV-1 integrase: involvement of both the core and carboxyl-terminal domains in multimerization. By systematic replacement of hydrophobic residues, we previously identified a single amino acid change (F185K) that dramatically improved the solubility of the catalytic domain of HIV-1 integrase and enabled the structure to be determined by x-ray crystallography. 1996 The Journal of biological chemistry Abstract HIV F185K 104 109 IN 186 195 8638110 Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. (ii) Unlike wild-type HIV, growth of M184V HIV in cell culture in the presence of d4T, AZT, Nevirapine, Delavirdine, or Saquinavir did not select for variants displaying drug resistance. 1996 Science (New York, N.Y.) Abstract HIV M184V 37 42 8638110 Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. (iii) There was an increase in fidelity of nucleotide insertion by the M184V mutant compared with wild-type enzyme. 1996 Science (New York, N.Y.) Abstract HIV M184V 71 76 8638110 Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. Monotherapy with (-)2',3'-dideoxy-3'-thiacytidine (3TC) leads to the appearance of a drug-resistant variant of human immunodeficiency virus-type 1 (HIV-1) with the methionine-184 --> valine (M184V) substitution in the reverse transcriptase (RT). 1996 Science (New York, N.Y.) Abstract HIV M184V;M184V 191;164 196;189 RT;RT 218;241 239;243 8642636 Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication. Certain amino acid substitutions in the reverse transcriptase (RT), including D67N, K70R, T215Y, and K219Q, cause high-level resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine (3'-azidothymidine; AZT) and appear to approximate the template strand of the enzyme-template-primer complex in structural models. 1996 Journal of virology Abstract HIV D67N;K219Q;K70R;T215Y 78;101;84;90 82;106;88;95 RT;RT 40;63 61;65 8642636 Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication. The results confirm that RT mutations D67N, K70R, T215Y, and K219Q affect an enzyme-template-primer interaction in vitro and suggest that such substitutions may affect HIV-1 pathogenesis during therapy by increasing viral replication capacity in cells stimulated after infection. 1996 Journal of virology Abstract HIV D67N;K219Q;K70R;T215Y 38;61;44;50 42;66;48;55 RT 25 27 8643685 Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors. The clone-purified RF (G48V/A71T/V82A) virus, unlike the corresponding defective NL4-3 triple mutant, grew well and displayed cross-resistance to four distinct protease inhibitors. 1996 Proc Natl Acad Sci U S A Abstract HIV G48V;A71T;V82A 23;28;33 27;32;37 PR 160 168 8643685 Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors. The predominant breakthrough virus contained the G48V/A71T/V82A protease mutations. 1996 Proc Natl Acad Sci U S A Abstract HIV A71T;G48V;V82A 54;49;59 58;53;63 PR 64 72 8648209 In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: mutations, kinetics, and frequencies. A Leu90-->Met exchange was the predominant resistance mutation in vivo; Gly48-->Val or doubly mutant virus was rarely observed. 1996 The Journal of infectious diseases Abstract HIV G48V;L90M 72;2 83;13 8648209 In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: mutations, kinetics, and frequencies. There was a good relationship between genotypic analysis of saquinavir resistance and data from virus assays, confirming that Leu90-->Met and Gly48-->Val are the essential exchanges in the proteinase that determine loss of sensitivity to this inhibitor. 1996 The Journal of infectious diseases Abstract HIV G48V;L90M 142;126 153;137 8648704 (Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes. Biochemical and phenotypic characterization of AAP-BHAPresistant HIV-1IIIB variants revealed that high-level resistance to the AAP-BHAPs was mediated by a Gly-190->Glu substitution in RT, which had a deleterious effect on the integrity and enzymatic activity of virion-associated RT heterodimers, as well as the replication capacity of these resistant viruses. 1996 Journal of virology Abstract HIV G190E 155 167 RT;RT 184;280 186;282 8648704 (Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes. Moreover, U-104489 demonstrated potent activity against BHA-P-resistant HIV-1MF harboring the Pro-236->Leu RT substitution and significantly suppressed the replication of clinical isolates of HIV-1 resistant to both delavirdine (BHAP U-90152T) and zidovudine. 1996 Journal of virology Abstract HIV P236L 94 106 RT 107 109 8652558 Role of methionine 184 of human immunodeficiency virus type-1 reverse transcriptase in the polymerase function and fidelity of DNA synthesis. The kinetic parameters governing DNA synthesis directed by RNA and DNA templates indicated that both M184A and M184V mutants are catalytically as efficient as the wild type enzyme. 1996 Biochemistry Abstract HIV M184A;M184V 101;111 106;116 8652558 Role of methionine 184 of human immunodeficiency virus type-1 reverse transcriptase in the polymerase function and fidelity of DNA synthesis. The M184V mutant exhibited a 25-45-fold increase in mismatch selectivity (ratio of k(cat)/K(m) of correct versus incorrect nucleotides) as compared to the WT enzyme. 1996 Biochemistry Abstract HIV M184V 4 9 8652558 Role of methionine 184 of human immunodeficiency virus type-1 reverse transcriptase in the polymerase function and fidelity of DNA synthesis. The nature of error-prone synthesis by the M184A mutant shows an increase in both the mismatch synthesis and extension of the mismatched primer termini. 1996 Biochemistry Abstract HIV M184A 43 48 8652592 Regulation of HIV-1 protease activity through cysteine modification. Recombinant protease mutants (C67A, C95A, and the double mutant C67A,C95A) were prepared to assess the possible role of these cysteines in redox regulation of the enzyme. 1996 Biochemistry Abstract HIV C67A;C67A;C95A;C95A 30;64;69;36 34;70;73;40 PR 12 20 8662780 Contribution of arginine residues in the RP135 peptide derived from the V3 loop of gp120 to its interaction with the Fv fragment of the 0.5beta HIV-1 neutralizing antibody. The mutations R4A, R8A and R11A (which correspond to residues 311, 315, and 318 in gp120 of HIV-1IIIB) reduce the binding free energy by 0.22 (+/- 0. 1996 The Journal of biological chemistry Abstract HIV R11A;R4A;R8A 27;14;19 31;17;22 gp120 83 88 8662909 Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate. In contrast to M184A RT, the Km and kcat values of M184V RT for dNTP substrates were similar to those of wt RT. 1996 The Journal of biological chemistry Abstract HIV M184A;M184V 15;51 20;56 RT;RT;RT 21;57;108 23;59;110 8662909 Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate. Mutations were made in recombinant human immunodeficiency virus type-1 reverse transcriptase (RT) by substituting methionine 184 with alanine (M184A) or valine (M184V), and steady-state and pre-steady-state kinetic constants were determined. 1996 The Journal of biological chemistry Abstract HIV M184A;M184A;M184V 143;114;161 148;141;166 RT;RT 71;94 92;96 8662909 Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate. The Kd and kp values of wt RT and M184V RT for dCTP and cis-5-fluoro-1-[2-(hydroxymethyl)-1, 3-oxathiolan-5-yl]cytosine 5'-triphosphate (1-beta-L-FTCTP) were estimated from pre-steady-state kinetics for single nucleotide incorporation. 1996 The Journal of biological chemistry Abstract HIV M184V 34 39 RT;RT 27;40 29;42 8662909 Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate. The Kd value of M184V RT for 1-beta-L-FTCTP was 19-fold greater than that of wt RT; the kpvalues of the two enzymes were similar. 1996 The Journal of biological chemistry Abstract HIV M184V 16 21 RT;RT 22;80 24;82 8662909 Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate. The Ki values of M184V RT for 1-beta-L-nucleoside analogs were increased 30-500-fold relative to wt RT for both RNA- and DNA-directed synthesis. 1996 The Journal of biological chemistry Abstract HIV M184V 17 22 RT;RT 23;100 25;102 8662909 Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate. The Km values of M184A RT for dNTPs were larger than those of wt RT for RNA-directed synthesis; the kcat values of M184A RT for processive or distributive synthesis were similar. 1996 The Journal of biological chemistry Abstract HIV M184A;M184A 17;115 22;120 RT;RT;RT 23;65;121 25;67;123 8663409 Kinetic characterization of human immunodeficiency virus type-1 protease-resistant variants. For the I50V mutant, the efficiency (kcat/Km) of processing peptides designed to mimic cleavage junctions in the HIV-1 gag-pol polypeptide was decreased up to 25-fold. 1996 The Journal of biological chemistry Abstract HIV I50V 8 12 GagPol 119 126 8663409 Kinetic characterization of human immunodeficiency virus type-1 protease-resistant variants. The triple mutant had a 2-fold higher processing efficiency than the I50V single mutant for peptide substrates with Phe/Pro and Tyr/Pro cleavage sites, suggesting that the M46I and I47V mutations are compensatory. 1996 The Journal of biological chemistry Abstract HIV I47V;I50V;M46I 181;69;172 185;73;176 8663409 Kinetic characterization of human immunodeficiency virus type-1 protease-resistant variants. These analyses support the virological observation that the addition of M46I and I47V mutations on the I50V mutant background enables increased survival of the HIV-1 virus as it replicates in the presence of VX-478. 1996 The Journal of biological chemistry Abstract HIV I47V;I50V;M46I 81;103;72 85;107;76 8663409 Kinetic characterization of human immunodeficiency virus type-1 protease-resistant variants. We have characterized recombinant HIV-1 proteases that contain these mutations either individually (L10F, M46I, I47V, I50V) or in combination (the double mutant L10F/I50V and the triple mutant M46I/I47V/I50V). 1996 The Journal of biological chemistry Abstract HIV I47V;I50V;M46I;I47V;I50V;I50V;L10F;L10F;M46I 198;203;193;112;118;166;100;161;106 202;207;197;116;122;170;104;165;110 PR 40 49 8663586 Protein orientation in the Tat-TAR complex determined by psoralen photocross-linking. We synthesized a 35-amino acid fragment containing arginine-rich RNA-binding domain of Tat (38-72), and replaced Arg57 with Cys to introduce a unique thiol group (-SH) in our model peptide. 1996 The Journal of biological chemistry Abstract HIV R57C 113 127 Tat 87 90 8669892 Inhibition of human immunodeficiency virus type 1 wild-type and mutant reverse transcriptases by the phenyl ethyl thiazolyl thiourea derivatives trovirdine and MSC-127. The prototype compound trovirdine (LY 300046 HCl) and one analogue, MSC-127, have been studied with respect to inhibition of wild-type HIV-1 RT and RT with various mutations known to give rise to resistance to other non-nucleoside RT inhibitors, namely Leu100-->Ile (Ile100), Glu138-->Arg (Arg138), Tyr181-->Cys (Cys181) and Tyr188-->His (His188). 1995 Antiviral research Abstract HIV E138R;L100I;Y181C;Y188H 276;253;299;325 288;265;311;337 RT;RT;RT 141;148;231 143;150;233 8676496 Effects of modifying the tRNA(3Lys) anticodon on the initiation of human immunodeficiency virus type 1 reverse transcription. In this work, the anticodon in a tRNA(3Lys) gene was changed from UUU to CUA (tRNA(3Lys)Su+) or, in addition, G-73 was altered to A (tRNA(3Lys)Su+G73A). 1996 Journal of virology Abstract HIV G73A;G73A 110;146 131;150 8676496 Effects of modifying the tRNA(3Lys) anticodon on the initiation of human immunodeficiency virus type 1 reverse transcription. tRNA(3Lys)Su+G73A has 60% of the wild-type ability to prime RT but competes poorly with wild-type tRNA(3Lys) for priming RT. 1996 Journal of virology Abstract HIV G73A 13 17 RT;RT 60;121 62;123 8676518 Increased polymerase fidelity of E89G, a nucleoside analog-resistant variant of human immunodeficiency virus type 1 reverse transcriptase. The E89G RT was previously shown to be resistant to several ddNTPs and to phosphonoformic acid. 1996 Journal of virology Abstract HIV E89G 4 8 RT 9 11 8676518 Increased polymerase fidelity of E89G, a nucleoside analog-resistant variant of human immunodeficiency virus type 1 reverse transcriptase. To evaluate the possible impact of such mutations on the ability of human immunodeficiency virus RT to selectively incorporate Watson-Crick base-paired deoxynucleotide triphosphates (dNTPs) over incorrectly paired dNTPs, we have measured the fidelity of dNTP insertion by the E89G variant of RT in in vitro reaction mixtures containing synthetic template primers. 1996 Journal of virology Abstract HIV E89G 276 280 RT;RT 97;292 99;294 8680883 Wild-type and transactivation-defective mutants of human immunodeficiency virus type 1 Tat protein bind human TATA-binding protein in vitro. Site-directed mutations within the activation domain of Tat (C22G and P18IS) that abrogate transactivation by Tat in vivo fail to inhibit Tat-TBP binding. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV C22G;P18I;P18S 61;70;70 66;75;75 Tat;Tat;Tat 56;110;138 59;113;141 8681387 Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain. The crystal structure of the conserved core of HIV-1 Nef has been determined in complex with the SH3 domain of a mutant Fyn tyrosine kinase (a single amino acid substitution, Arg-96 to isoleucine), to which Nef binds tightly. 1996 Cell Abstract HIV R96I 175 195 Nef;Nef 53;207 56;210 8692823 A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency. A compensatory mutation in TAR (G28 -> A), designed to reestablish base pairing in the TAR hairpin, restored wild-type Tat responsiveness. 1996 Proc Natl Acad Sci U S A Abstract HIV G28A 32 40 Tat 119 122 8692823 A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency. Cloning of a region corresponding to the 5'-LTR from ACH2, however, identified a point mutation (C37 -> T) in TAR. 1996 Proc Natl Acad Sci U S A Abstract HIV C37T 97 105 LTR 44 47 8692823 A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency. When the (C37 -> T) mutation was introduced in an infectious clone of HIV-1, no viral production was measured in the absence of TNF-alpha, whereas full complementation was observed when the infection was conducted in the presence of TNF-alpha or when a compensatory mutation (G28 -> A) was introduced into TAR. 1996 Proc Natl Acad Sci U S A Abstract HIV C37T;G28A 10;276 18;284 8700148 Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication. They were also highly efficient (EC50 < or = 0.02 microgram/ml) in suppressing the replication of mutant virus strains that contained mutations in their reverse transcriptase that conferred resistance to other non-nucleoside reverse transcriptase inhibitors (i.e., Tyr181 to Cys, Lys103 to Asn, Val106 to Ala, and Leu100 to Ile). 1996 Molecular pharmacology Abstract HIV K103N;L100I;V106A;Y181C 280;314;295;265 293;327;308;278 NNRTI;RT 210;153 246;174 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. Depending on the template/primer (T/P) used, the total incorporation of nucleotides under single processive cycle conditions was 20-50% higher with K65R RT than with wt RT. 1996 The Journal of biological chemistry Abstract HIV K65R 148 152 RT;RT 153;169 155;171 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. However, under single processive cycle conditions, the rate of full-length polymerization product synthesis by K65R RT was about 2-fold higher than that by wt RT. 1996 The Journal of biological chemistry Abstract HIV K65R 111 115 RT;RT 116;159 118;161 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. The K65R mutation in HIV-1 reverse transcriptase (RT) is associated with viral cross-resistance to 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, and 2',3'-dideoxy-3'-thiacytidine. 1996 The Journal of biological chemistry Abstract HIV K65R 4 8 RT;RT 27;50 48;52 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. We also found a decreased rate of T/P dissociation during K65R RT DNA synthesis, which is consistent with the increased processivity of the enzyme. 1996 The Journal of biological chemistry Abstract HIV K65R 58 62 RT 63 65 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. We have found that in vitro DNA synthesis by K65R RT is significantly more processive than that of wild type (wt) RT. 1996 The Journal of biological chemistry Abstract HIV K65R 45 49 RT;RT 50;114 52;116 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. We postulate that the increased processivity of the K65R RT may be a compensatory response to the decreased affinity of this mutant for certain dNTP substrates, allowing normal viral replication kinetics. 1996 The Journal of biological chemistry Abstract HIV K65R 52 56 RT 57 59 8702696 The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. With heteropolymeric T/P, the total incorporation of dNMP by K65R and wt RT was similar under continuous DNA synthesis reaction conditions. 1996 The Journal of biological chemistry Abstract HIV K65R 61 65 RT 73 75 8703945 A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation. A primer-extension assay that allowed determination of DNA elongation by the G190E mutant RT on a heteropolymeric HIV-1 gag-based RNA template showed an overall decrease in DNA polymerization. 1996 Biochemistry Abstract HIV G190E 77 82 Gag;RT 120;90 123;92 8703945 A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation. It is concluded that the deleterious effect of the G190E resistance mutation on both of these RT functions is most likely involved in the observed retarded replication capacity of the AAP-BHAP-(U-104489-) resistant HIV-1. 1996 Biochemistry Abstract HIV G190E 51 56 RT 94 96 8703945 A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation. Selection of the IIIB strain of human immunodeficiency virus type (HIV-1) resistant to the (alkylamino)piperidine-bis(heteroaryl)piperazine (AAP-BHAP) U-104489 results in substitution of a glycine to glutamate at residue 190 (G190E) of reverse transcriptase (RT). 1996 Biochemistry Abstract HIV G190E;G190E 226;189 231;224 RT;RT 236;259 257;261 8703945 A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation. The size distribution of products generated by G190E RT-associated RNase H digestion of RNA from [35S]poly(rA).poly(dT) was markedly distinct from that of the G190A RT and was consistent with the observed reduction in RT-associated RNase H activity of the G190E RT. 1996 Biochemistry Abstract HIV G190A;G190E;G190E 159;47;256 164;52;261 RT;RT;RT;RT 53;165;218;262 55;167;220;264 8703945 A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation. We report here that the G190E mutation in recombinant heterodimeric HIV-1 RT, compared to the wild-type RT (G190) or a G190A control mutant, results in a 40% and 80% reduction in the polymerase and RNase H specific enzymatic activities, respectively. 1996 Biochemistry Abstract HIV G190A;G190E 119;24 124;29 Pol;RT;RT 183;74;104 193;76;106 8703945 A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation. When challenged with unlabeled substrates, the G190E RT was relatively nonprocessive with respect to DNA synthesis and RNA degradation. 1996 Biochemistry Abstract HIV G190E 47 52 RT 53 55 8709096 Pyrrolobenzothiazepinones and pyrrolobenzoxazepinones: novel and specific non-nucleoside HIV-1 reverse transcriptase inhibitors with antiviral activity. In enzyme assay although 16e inhibited HIV-1 RT, it was inactive against the nevirapine-resistant recombinant RT Y181C at 50 microM. 1996 Journal of medicinal chemistry Abstract HIV Y181C 113 118 RT;RT 45;110 47;112 8709193 Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication. Strikingly, the I kappa B alpha (S32A, S36A) transdominant mutant was at least five times as effective as wild-type I kappa B alpha in inhibiting synergistic induction of the HIV-1 LTR. 1996 Journal of virology Abstract HIV S32A;S36A 33;39 37;43 LTR 181 184 8709193 Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication. The synergistic induction of HIV-1 LTR-driven gene expression represented a 50- to 70-fold stimulation and required both an intact HIV-1 enhancer and Tat-TAR element interaction, since mutations in Tat protein (R52Q, R53Q) or in the bulge region of the TAR element that eliminated Tat binding to TAR were unable to stimulate LTR expression. 1996 Journal of virology Abstract HIV R52Q;R53Q 211;217 215;221 LTR;LTR;Tat;Tat;Tat 35;325;150;198;281 38;328;153;201;284 8709193 Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication. Transdominant forms of I kappa B alpha, mutated in critical serine or threonine residues required for inducer-mediated (S32A, S36A) and/or constitutive (S283A, T291A, T299A) phosphorylation of I kappa B alpha were tested for their capacity to block HIV-1 LTR transactivation. 1996 Journal of virology Abstract HIV S283A;S32A;S36A;T291A;T299A 153;120;126;160;167 158;124;130;165;172 LTR 255 258 8709214 Significance of amino acid variation at human immunodeficiency virus type 1 reverse transcriptase residue 210 for zidovudine susceptibility. Amino acid variation at reverse transcriptase (RT) codon 210 (generally Leu-210 to Trp [L210W], TTG-->TGG) is occasionally detected after the initiation of azidothymidine (AZT) therapy. 1996 Journal of virology Abstract HIV L210W;L210W 88;72 93;86 RT;RT 24;47 45;49 8709214 Significance of amino acid variation at human immunodeficiency virus type 1 reverse transcriptase residue 210 for zidovudine susceptibility. In summary, the L210W mutation appears to be of marginal significance, conferring approximately two- to fourfold-reduced sensitivity to AZT compared with similar AZT-resistant genomes with L-210. 1996 Journal of virology Abstract HIV L210W 16 21 8709214 Significance of amino acid variation at human immunodeficiency virus type 1 reverse transcriptase residue 210 for zidovudine susceptibility. The frequency and genetic background of the L210W mutation in vivo were assessed by analyzing sera of AZT-naive and AZT-experienced patients by RT-PCR and DNA sequencing. 1996 Journal of virology Abstract HIV L210W 44 49 RT 144 146 8718851 Crystal structures of complexes of a peptidic inhibitor with wild-type and two mutant HIV-1 proteases. All structures have been determined to 2.3 A resolution and have satisfactory agreement factors: 0.173 for wild type, 0.175 for V82D, and 0.182 for V82N. 1996 Biochemistry Abstract HIV V82D;V82N 128;148 132;152 8718851 Crystal structures of complexes of a peptidic inhibitor with wild-type and two mutant HIV-1 proteases. Crystal structures of the protease of human immunodeficiency virus type 1 (HIV-1) and two mutant proteases, V82D and V82N, have been determined. 1996 Biochemistry Abstract HIV V82D;V82N 108;117 112;121 PR;PR 26;97 34;106 8718851 Crystal structures of complexes of a peptidic inhibitor with wild-type and two mutant HIV-1 proteases. In the V82D crystal structure, a water molecule, which connects the protease flap to the inhibitor, is missing or of low occupancy. 1996 Biochemistry Abstract HIV V82D 7 11 PR 68 76 8718851 Crystal structures of complexes of a peptidic inhibitor with wild-type and two mutant HIV-1 proteases. The V82D mutant possesses these qualities. 1996 Biochemistry Abstract HIV V82D 4 8 8721556 Reduced sensitivity to saquinavir: an update on genotyping from phase I/II trials. Genotypic resistance was defined by the Gly48-->Val and Leu90-->Met exchanges. 1996 Antiviral research Abstract HIV G48V;L90M 40;56 51;67 8756683 Human immunodeficiency virus protease ligand specificity conferred by residues outside of the active site cavity. SB203386 is a potent inhibitor of HIV-1 protease (Ki = 18 nM) but shows decreased inhibition of the HIV-1 protease (Val32Ile, Ile47Val, Val82Ile) triple mutant (Ki = 112 nM) and SIV protease (Ki = 960 nM). 1996 Biochemistry Abstract HIV I47V;V32I;V82I 126;116;136 134;124;144 PR;PR;PR 40;106;182 48;114;190 8756683 Human immunodeficiency virus protease ligand specificity conferred by residues outside of the active site cavity. To gain greater understanding of the structural basis of human immunodeficiency virus (HIV) protease ligand specificity, we have crystallized and determined the structures of the HIV-1 protease (Val32Ile, Ile47Val, Val82Ile) triple mutant and simian immunodeficiency virus (SIV) protease in complex with SB203386, a tripeptide analogue inhibitor containing a C-terminal imidazole substituent as an amide bond isostere. 1996 Biochemistry Abstract HIV I47V;V32I;V82I 205;195;215 213;203;223 PR;PR;PR 92;185;279 100;193;287 8764018 Structural analysis of human immunodeficiency virus type 1 Gag protein interactions, using cysteine-specific reagents. Mutagenesis of C-350 to a serine residue in the mutant C350S (C-350 changed to serine) virtually eliminated particle assembly, attesting to the importance of this region. 1996 Journal of virology Abstract HIV C350S 55 60 8764018 Structural analysis of human immunodeficiency virus type 1 Gag protein interactions, using cysteine-specific reagents. We also examined a C330S mutant, as well as mutants in which cysteines were created midway through the capsid domain or in the C-terminal section of the major homology region. 1996 Journal of virology Abstract HIV C330S 19 24 Capsid 103 109 8764080 Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1. Fully endogenous RT assays showed that viruses containing the M184V substitution were highly resistant to 3TCTP, with an increase in the 50% inhibitory concentration of 250-fold in comparison with wild-type recombinant virus. 1996 Journal of virology Abstract HIV M184V 62 67 RT 17 19 8764080 Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1. Kinetic analysis showed that the Ki values and the Ki/Km ratios for mutated, recombinant M184V human immunodeficiency virus type 1 reverse transcriptase (RT) for (-)2'-dideoxy-3'-thiacytidine triphosphate (3TCTP) were 35-fold higher than the equivalent values for wild-type RT but only about twice as high as the equivalent values for each of the triphosphates of ddC (ddCTP) and ddA (ddATP). 1996 Journal of virology Abstract HIV M184V 89 94 RT;RT;RT 131;154;274 152;156;276 8764985 Mutational studies of human immunodeficiency virus type 1 reverse transcriptase: the involvement of residues 183 and 184 in the fidelity of DNA synthesis. The first mutant, Met 184-->Leu (M184L), displays a marked reduction in both misinsertion and mispair extension, suggesting a fidelity of DNA synthesis significantly higher than that of the wild-type HIV-1 RT. 1996 FEBS letters Abstract HIV M184L;M184L 33;18 38;31 RT 206 208 8764985 Mutational studies of human immunodeficiency virus type 1 reverse transcriptase: the involvement of residues 183 and 184 in the fidelity of DNA synthesis. The second mutant, Tyr 183-->Phe (Y183F), shows a decrease in mispair extension with no significant change in misincorporation. 1996 FEBS letters Abstract HIV T183P;Y183F 19;34 32;39 8764985 Mutational studies of human immunodeficiency virus type 1 reverse transcriptase: the involvement of residues 183 and 184 in the fidelity of DNA synthesis. Thus, the overall pattern of error-proneness of DNA synthesis is: wild-type HIV-1 RT > Y183F > M184L. 1996 FEBS letters Abstract HIV M184L;Y183F 95;87 100;92 RT 82 84 8783803 New arylpyrido-diazepine and -thiodiazepine derivatives are potent and highly selective HIV-1 inhibitors targeted at the reverse transcriptase. An HIV-1 strain containing the 188 Tyr-->His mutation in the reverse transcriptase displayed severely reduced sensitivity to the compounds. 1996 Antiviral research Abstract HIV Y188H 31 44 RT 61 82 8794364 Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet. Highly PFA-resistant HIV- 1 strains were hypersusceptible to AZT; conversely, AZT-resistant strains with M41L and T215Y; M41L, L210W, and T215Y; or M41L, D67N, K70R, and T215Y mutations were 2.2- to 2.5-fold hypersusceptible to PFA. 1996 Journal of virology Abstract HIV D67N;K70R;L210W;M41L;M41L;M41L;T215Y;T215Y;T215Y 154;160;127;105;121;148;114;138;170 158;164;132;109;125;152;119;143;175 8794364 Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet. Phenotypic reversion of AZT resistance by W88S, W88G, E89K, L921, and S156A was associated with a concomitant suppression of PFA resistance. 1996 Journal of virology Abstract HIV E89K;S156A;W88G;W88S 54;70;48;42 58;75;52;46 8794364 Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet. The introduction of the previously identified PFA resistance mutation W to G at codon 88 (W88G), E89K, L92I, or Q161L into an HIV-1 strain having the four known AZT resistance mutations completely reversed high-level AZT resistance. 1996 Journal of virology Abstract HIV E89K;L92I;Q161L;W88G 97;103;112;90 101;107;117;94 8794364 Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet. Two additional PFA resistance mutations, W88S and S156A, partially suppressed AZT resistance. 1996 Journal of virology Abstract HIV S156A;W88S 50;41 55;45 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. Analysis of virion-associated reverse transcriptase activity indicated that the Lys70Arg mutation resulted in an enzyme with 2- to 4-fold decreased susceptibility to ddATP. 1996 Virology Abstract HIV K70R 80 88 RT 30 51 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. Drug susceptibility assays on the virus with Lys70Arg mutation showed a marginal decrease in susceptibility to ddl (1.5- to 2-fold) and about 4- to 6-fold decrease in susceptibility to AZT. 1996 Virology Abstract HIV K70R 45 53 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. Mutations Lys65Glu and Arg72Ser resulted in an impaired RT with greatly diminished functional RT activity. 1996 Virology Abstract HIV K65E;R72S 10;23 18;31 RT;RT 56;94 58;96 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. Sequence and nested PCR analysis of the HIV-1 RT gene revealed that two viral isolates contained the Leu to Val change at codon 74, and three other isolates with reduced susceptibility to ddl each contained changes at codons 65, 70, and 72. 1996 Virology Abstract HIV L74V 101 130 RT 46 48 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. Statistical analysis of the inhibitory concentration for RT activity between pNL4-3 and mutant Lys70Arg viruses obtained in three independent RT inhibition assays was significant (P = 0.05) by student t test paired analysis. 1996 Virology Abstract HIV K70R 95 103 RT;RT 57;142 59;144 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. The AZT-associated Lys70Arg mutation results in an RT enzyme with decreased susceptibility to ddATP. 1996 Virology Abstract HIV K70R 19 27 RT 51 53 8806572 AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. The genetic basis for didanosine (ddl) resistance in human immunodeficiency virus (HIV-1) has previously been shown to be commonly associated with a Leu to Val change at codon 74 in the HIV-1 RT gene. 1996 Virology Abstract HIV L74V 149 178 RT 192 194 8806575 Interaction between the cytoplasmic domains of HIV-1 Vpu and CD4: role of Vpu residues involved in CD4 interaction and in vitro CD4 degradation. Deletion of the C-terminal residues of Vpu, required for CD4 degradation, as well as the double mutation on the casein kinase II phosphorylation sites S52N-S56N, also involved in CD4 degradation, resulted in the loss of interaction with CD4 and in the inability to induce CD4 degradation. 1996 Virology Abstract HIV S52N;S56N 151;156 155;160 Vpu 39 42 8806671 Phosphorylation of HIV-1 Rev protein: implication of protein kinase CK2 and pro-directed kinases. In contrast, a mutation (R14TV-->EED) which suppresses Rev activity dramatically enhances Rev phosphorylation either in vitro by CK2 or in vivo, suggesting that phosphorylation by CK2 could play a role in Rev down-regulation. 1996 Biochemical and biophysical research communications Abstract HIV R14T;R14V 25;25 30;30 Rev;Rev;Rev 55;90;205 58;93;208 8807067 The nucleoside analog-resistant E89G mutant of human immunodeficiency virus type 1 reverse transcriptase displays a broader cross-resistance that extends to nonnucleoside inhibitors. Because the nonnucleoside inhibitor-binding pocket is adjacent to the deoxynucleoside triphosphate substrate-binding site, the impact of the E89G reverse transcriptase has decreased susceptibility to TIBO R82150, nevirapine, and to a lesser extent, delavirdine. 1996 Antimicrobial agents and chemotherapy Abstract HIV E89G 141 145 RT 146 167 8807067 The nucleoside analog-resistant E89G mutant of human immunodeficiency virus type 1 reverse transcriptase displays a broader cross-resistance that extends to nonnucleoside inhibitors. The alteration of a glutamic acid (E) to a glycine (G) amino acid residue at position 89 (E89G alteration) in the human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to several nucleoside analog inhibitors. 1996 Antimicrobial agents and chemotherapy Abstract HIV E89G 90 95 RT 150 171 8809165 Targeting delavirdine/atevirdine resistant HIV-1: identification of (alkylamino)piperidine-containing bis(heteroaryl)piperazines as broad spectrum HIV-1 reverse transcriptase inhibitors. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-BHAPs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). 1996 Journal of medicinal chemistry Abstract HIV P236L;Y181C 275;265 280;270 RT 248 251 8815692 Delavirdine mesylate, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor. The most common genotypic mutations seen to date are K103N and P236L. 1996 Advances in experimental medicine and biology Abstract HIV K103N;P236L 53;63 58;68 8815692 Delavirdine mesylate, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor. The pharmacokinetics are non-linear as DLV is metabolized primarily by cytochrome P4503A in the liver. 1996 Advances in experimental medicine and biology Abstract HIV P4503A 82 88 8825619 Design, synthesis, and resistance patterns of MP-134 and MP-167, two novel inhibitors of HIV type 1 protease. An isoleucine-to-valine substitution at residue 84 (I84V) of the HIV-1 protease confers resistance to MP-134, whereas a glycine-to-valine substitution at residue 48 (G48V) confers resistance to MP-167. 1996 AIDS research and human retroviruses Abstract HIV G48V;G48V;I84V;I84V 166;120;52;3 170;164;56;50 PR 71 79 8834868 Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Consistent with these findings, reductions in susceptibility were observed for recombinant viruses constructed to contain the single I84V change or the double M46I+I84V substitutions. 1996 Antimicrobial agents and chemotherapy Abstract HIV I84V;I84V;M46I 133;164;159 137;168;163 8834868 Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Molecular analysis of the protease from this variant indicated a double change from a Met to Ile at residue 46 and an Ile to Val or Ala at residue 84 (M46I+I84V, A). 1996 Antimicrobial agents and chemotherapy Abstract HIV I84V;M46I;M46I 156;151;86 160;155;110 PR 26 34 8834868 Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Resistance, however, was not detected for recombinant viruses containing other key mutations in HIV-1 protease, including a Val to Ile change at residue 32 or a Val to Ala or Phe at residue 82. 1996 Antimicrobial agents and chemotherapy Abstract HIV V32I 124 155 PR 102 110 8843229 Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype. At study entry, plasma from 4 subjects had human immunodeficiency virus RNA pol T215Y/F mutant and 4 had codon 215 wild type. 1996 The Journal of infectious diseases Abstract HIV T215F;T215Y 80;80 87;87 Pol 76 79 8843229 Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype. No subject developed a pol L74V codon mutation. 1996 The Journal of infectious diseases Abstract HIV L74V 27 31 Pol 23 26 8843229 Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype. Sustained 10-fold decreases in plasma RNA levels were seen only in subjects who initially had 215 wild type RNA, despite the development of a T215Y/F mutation during combination therapy. 1996 The Journal of infectious diseases Abstract HIV T215F;T215Y 142;142 149;149 8853733 Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538). Additional mutations found in more than one patient were I15V, M36I, I84V and I93L. 1996 AIDS (London, England) Abstract HIV I15V;I84V;I93L;M36I 57;69;78;63 61;73;82;67 8853733 Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538). However, at week 78, mutations R8Q, E34K, R57K, L63P and I84V were detected and the treatment benefit was partially lost. 1996 AIDS (London, England) Abstract HIV E34K;I84V;L63P;R57K;R8Q 36;57;48;42;31 40;61;52;46;34 8853733 Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538). Mutation L63P was found both in pre- and post-ritonavir samples. 1996 AIDS (London, England) Abstract HIV L63P 9 13 8853733 Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538). RESULTS: The most frequent amino-acid substitutions occurring upon administration of the protease inhibitor were V82A/F (substrate binding site), I54V (flap region), A71V and L10I. 1996 AIDS (London, England) Abstract HIV A71V;I54V;L10I;V82A;V82F 166;146;175;113;113 170;150;179;119;119 PR 89 97 8853733 Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538). The mutations L10I, I54V, L63P, A71V, V82A/F and I84V correspond to known drug-resistance mutations for ritonavir and other protease inhibitors. 1996 AIDS (London, England) Abstract HIV A71V;I54V;I84V;L10I;L63P;V82A;V82F 32;20;49;14;26;38;38 36;24;53;18;30;44;44 PR 124 132 8856082 A synthetic peptide from the human immunodeficiency virus type-1 integrase exhibits coiled-coil properties and interferes with the in vitro integration activity of the enzyme. Correlated biochemical and spectroscopic results. Here, we report some of the structural and functional properties of two synthetic peptides: integrase-(147-175)-peptide reproducing the residues 147-175 (SQGVVESMNKELK159KIIGQVRDQAEHLKTAY) of the HIV-1 integrase, and [Pro159] integrase-(147-175)-peptide where the lysine 159 is substituted for a proline. 1996 European journal of biochemistry Abstract HIV K159P 264 303 IN;IN;IN 92;202;226 101;211;235 8861970 Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis. Misinsertion fidelity assays revealed that mutants Y115W, Y115A and Y115S had a higher misinsertion efficiency than the wild-type reverse transcriptase. 1996 The EMBO journal Abstract HIV Y115A;Y115S;Y115W 58;68;51 63;73;56 RT 130 151 8861970 Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis. The activity of the variant enzymes having Trp, Ala or Ser instead of Tyr115 was reduced significantly, particularly when poly(rA)484 was used as template. 1996 The EMBO journal Abstract HIV Y115W;Y115A;Y115S 43;43;43 76;76;76 8861970 Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis. The effects observed on the steady state kinetic constants, processivity and fidelity were mediated by the 66 kDa subunit, as demonstrated using chimeric heterodimers with the Y115A substitution in either p66 or p51. 1996 The EMBO journal Abstract HIV Y115A 176 181 8861970 Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis. The substitution of Tyr115 by Phe renders a fully active polymerase, displaying similar kinetic parameters, processivity and misinsertion fidelity of DNA synthesis as the wild-type enzyme. 1996 The EMBO journal Abstract HIV Y115F 20 33 Pol 57 67 8876644 Human immunodeficiency virus (HIV) Nef is an RNA binding protein in cell-free systems. Moreover, a single amino acid replacement, Arg to Gly at position 22 produces a Nef variant deficient in its ability to interact with RNA. 1996 Journal of molecular biology Abstract HIV R22G 43 68 Nef 80 83 8878611 Novel mutation (K70E) in human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to 9-[2-(phosphonomethoxy)ethyl]adenine in vitro. A recombinant virus carrying the K70E mutation was constructed and showed a 10-fold increase in its 50% inhibitory concentrations of PMEA and 2',3'-dideoxy-3'-thiacytidine but showed wild-type susceptibility levels to 2',3'-dideoxycytosine, 2',3'-dideoxyinosine,2',3'-didehydro-2'3'-dideoxythymidine, 3'-azido-3'-deoxythymidine, foscarnet, and two additional phosphonates, 9-[(R)-2-(phosphonomethoxy)propyl]adenine and 9-[2,5-dihydro-5-(phosphonomethoxy)-2-furanyl]adenine. 1996 Antimicrobial agents and chemotherapy Abstract HIV K70E 33 37 8878611 Novel mutation (K70E) in human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to 9-[2-(phosphonomethoxy)ethyl]adenine in vitro. Additionally, the K70E recombinant showed a minor reduction in growth kinetics compared with those of the wild-type virus in vitro. 1996 Antimicrobial agents and chemotherapy Abstract HIV K70E 18 22 8878611 Novel mutation (K70E) in human immunodeficiency virus type 1 reverse transcriptase confers decreased susceptibility to 9-[2-(phosphonomethoxy)ethyl]adenine in vitro. Sequence analyses of these PMEA-selected viruses demonstrated the presence of a novel lysine-to-glutamic acid mutation at amino acid 70 (K70E) in HIV reverse transcriptase. 1996 Antimicrobial agents and chemotherapy Abstract HIV K70E;K70E 137;86 141;135 RT 150 171 8883581 Selection conditions affect the evolution of specific mutations in the reverse transcriptase gene associated with resistance to DMP 266. RESULTS: Passage in MT-2 cells resulted in accumulation of three substitutions in RT (V179D, L1001, Y181C) after 24 passages associated with 1000-fold reduced susceptibility to DMP 266. 1996 AIDS (London, England) Abstract HIV V179D;Y181C 86;100 91;105 RT 82 84 8891168 In vitro selection and molecular characterization of human immunodeficiency virus type 1 with reduced sensitivity to 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). HIV with the K65R mutation inserted by site-directed mutagenesis also had decreased sensitivity to PMEA in H9 cells and a similar cross-resistance profile. 1996 Antiviral research Abstract HIV K65R 13 17 8891168 In vitro selection and molecular characterization of human immunodeficiency virus type 1 with reduced sensitivity to 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). Sequencing of the RT encoding region of each of eight pol clones from resistant isolates revealed a Lys-65-->Arg (K65R) substitution. 1996 Antiviral research Abstract HIV K65R;K65R 114;100 118;112 Pol;RT 54;18 57;20 8891168 In vitro selection and molecular characterization of human immunodeficiency virus type 1 with reduced sensitivity to 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). Thus, HIV can develop decreased sensitivity to PMEA after long-term in vitro exposure and this change is associated with a K65R substitution. 1996 Antiviral research Abstract HIV K65R 123 127 8892962 Possible role of the V3 domain of gp120 in resistance to an amphotericin B derivative (MS8209) blocking human immunodeficiency virus entry. In the V3 domain of gp120, ROD(CEM) differed from ROD10 at two positions (a threonine instead of an isoleucine at position 312 and an arginine instead of a glutamine at position 329), and drug resistance was conferred to HIV-1 by substitution of the ROD(CEM) V3 but not the ROD10 V3. 1996 Journal of virology Abstract HIV Q329R;I312T 134;76 181;126 gp120 20 25 8896496 Multiple drug resistance to nucleoside analogues and nonnucleoside reverse transcriptase inhibitors in an efficiently replicating human immunodeficiency virus type 1 patient strain. Accumulation of drug resistance mutations (mainly V75I, F77L, K103N, F116Y, Q151M, and M184V) eventually resulted in a strain that was genotypically and phenotypically resistant to all tested ddNs and the majority of NNRTIs. 1996 The Journal of infectious diseases Abstract HIV F116Y;F77L;K103N;M184V;Q151M;V75I 69;56;62;87;76;50 74;60;67;92;81;54 NNRTI 217 223 8898668 A phase-I study of the safety, pharmacokinetics, and antiviral activity of combination didanosine and ribavirin in patients with HIV-1 disease. AIDS Clinical Trials Group 231 Protocol Team. The L74V ddI resistance-conferring HIV-I reverse-transcriptase mutation emerged in 53% of the patients. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV L74V 4 8 RT 41 62 8913459 Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection. In addition to the changes at positions 82 and 90, we have identified M46L/I, G48V, and I54V substitutions in isolates derived from indinavir-treated patients. 1996 Antimicrobial agents and chemotherapy Abstract HIV G48V;I54V;M46I;M46L 78;88;70;70 82;92;76;76 8913459 Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection. Patient human immunodeficiency virus type 1 (HIV-1) isolates that are resistant to protease inhibitors may contain amino acid substitutions L10I/V, M46L/I, G-48V, L63P, V82A/F/T, I84V, and L90M in the protease gene. 1996 Antimicrobial agents and chemotherapy Abstract HIV G48V;I84V;L10I;L10V;L63P;L90M;M46I;M46L;V82A;V82F;V82T 156;179;140;140;163;189;148;148;169;169;169 161;183;146;146;167;193;154;154;177;177;177 PR;PR 83;201 91;209 8913470 9-[2-(Phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques. Emergence of virus with fivefold-decreased susceptibility to PMPA occurred in all four PMPA-treated animals and was associated with the development of a lysine-to-arginine substitution at amino acid 65 (K65R mutation) and additional mutations in the reverse transcriptase; however, the clinical implications of this low-level drug resistance are nuclear. 1996 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R 203;153 208;201 RT 250 271 8917470 Expression, characterisation and mutagenesis of the aspartic proteinase from equine infectious anaemia virus. Mutant forms of EIAV proteinase (Thr30-->Asp and Ile54-->Gly) were generated and their ability to interact with substrates and inhibitors was characterised. 1996 European journal of biochemistry Abstract HIV I54G;T30D 49;33 60;45 Asp 41 44 8943242 Mutational anatomy of an HIV-1 protease variant conferring cross-resistance to protease inhibitors in clinical trials. Compensatory modulations of binding and activity. In contrast, the double substitutions of V82T and I84V are detrimental to the ability of the protease to bind and, thereby, to catalyze. 1996 The Journal of biological chemistry Abstract HIV I84V;V82T 50;41 54;45 PR 93 101 8943242 Mutational anatomy of an HIV-1 protease variant conferring cross-resistance to protease inhibitors in clinical trials. Compensatory modulations of binding and activity. Site-specific substitutions of as few as four amino acids (M46I/L63P/V82T/I84V) of the human immunodeficiency virus type 1 (HIV-1) protease engenders cross-resistance to a panel of protease inhibitors that are either in clinical trials or have recently been approved for HIV therapy (Condra, J. 1996 The Journal of biological chemistry Abstract HIV I84V;L63P;M46I;V82T 74;64;59;69 78;68;63;73 PR;PR 131;181 139;189 8943242 Mutational anatomy of an HIV-1 protease variant conferring cross-resistance to protease inhibitors in clinical trials. Compensatory modulations of binding and activity. Two of these mutations (V82T/I84V) are located in, while the other two (M46I/L63P) are away from, the binding cleft of the enzyme. 1996 The Journal of biological chemistry Abstract HIV M46I;V82T;I84V;L63P 72;24;29;77 76;28;33;81 8943242 Mutational anatomy of an HIV-1 protease variant conferring cross-resistance to protease inhibitors in clinical trials. Compensatory modulations of binding and activity. We have found that the double substitutions of M46I and L63P do not affect binding but instead endow the enzyme with a catalytic efficiency significantly exceeding (110-360%) that of the wild-type enzyme. 1996 The Journal of biological chemistry Abstract HIV L63P;M46I 56;47 60;51 8948367 Detection of HIV-1 infection with a green fluorescent protein reporter system. HeLa-CD4 cells transfected with the plasmid pRH1, which encodes GFP-S65T under the control of the HIV-1 LTR promoter, and either co-transfected with a plasmid encoding the HIV-1 tat product or superinfected with HIV-1, expressed high levels of GFP-S65T, which was readily detected by fluorescence microscopy and fluorescence-activated cell-sorting analysis. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV S65T;S65T 68;248 72;252 LTR;Tat;PR 104;178;44 107;181;46 8948367 Detection of HIV-1 infection with a green fluorescent protein reporter system. In the present study, the Aequorea green fluorescent protein S65T variant (GFP-S65T) was used in a reporter system for detecting HIV-1. 1996 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV S65T;S65T 61;79 65;83 8969180 Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex. In contrast, G48V and L90M/G48V proteases had catalytic efficiency (kcat/Km) values with TLNF-PISP, RKIL-FLDG, and AETF-YVDG that were 1/10 to 1/20 the value of WT protease. 1996 The Journal of biological chemistry Abstract HIV G48V;G48V;L90M 27;13;22 31;17;26 PR;PR 32;164 41;172 8969180 Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex. In contrast, the dissociation rate constants for WT, L90M, G48V, and L90M/G48V proteases complexed with saquinavir were 0.0014, 0.019, 0.128, and 0. 1996 The Journal of biological chemistry Abstract HIV G48V;G48V;L90M;L90M 74;59;53;69 78;63;57;73 PR 79 88 8969180 Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex. L90M, G48V, and L90M/G48V proteases have 1/20, 1/160, and 1/1000 the affinity for saquinavir compared to WT protease, respectively. 1996 The Journal of biological chemistry Abstract HIV G48V;G48V;L90M;L90M 21;6;16;0 25;10;20;4 PR;PR 26;108 35;116 8969180 Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex. Mutations in the human immunodeficiency virus (HIV) protease (L90M, G48V, and L90M/G48V) arise when HIV is passaged in the presence of the HIV protease inhibitor saquinavir. 1996 The Journal of biological chemistry Abstract HIV G48V;G48V;L90M;L90M 83;68;62;78 87;72;66;82 PR;PR 52;143 60;151 8969180 Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex. These mutations yield a virus with less sensitivity to the drug (L90M > G48V >> L90M/G48V). 1996 The Journal of biological chemistry Abstract HIV G48V;G48V;L90M;L90M 85;72;65;80 89;76;70;84 8969180 Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex. WT and L90M proteases had similar catalytic constants for these substrates. 1996 The Journal of biological chemistry Abstract HIV L90M 7 11 PR 12 21 8970671 Rational approaches to resistance: using saquinavir. Clinically, G48V is uncommon and the double mutation rare. 1996 AIDS (London, England) Abstract HIV G48V 12 16 8970671 Rational approaches to resistance: using saquinavir. L90M is the predominant mutation in vivo. 1996 AIDS (London, England) Abstract HIV L90M 0 4 8970671 Rational approaches to resistance: using saquinavir. RESISTANCE TO SAQUINAVIR: Resistance to saquinavir in vitro and in vivo is associated with mutations L90M and G48V in HIV protease. 1996 AIDS (London, England) Abstract HIV G48V;L90M 110;101 114;105 PR 122 130 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. In addition to the Ser substitution at Pro-109, P109SR had a second substitution of Ala for Thr at position 125 in integrase. 1996 Journal of virology Abstract HIV P109R;P109S;S109P;T125A 48;48;19;84 54;54;46;111 IN 115 124 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. P109S integrase did not display detectable 3' processing or DNA strand transfer activity, although 5 to 10% of wild-type disintegration activity was detected. 1996 Journal of virology Abstract HIV P109S 0 5 IN 6 15 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. P109S integrase ran as a large aggregate on a size exclusion column, whereas wild-type integrase ran as a monomer and P109S T125A integrase ran as a mixed population. 1996 Journal of virology Abstract HIV P109S;T125A;P109S 118;124;0 123;129;5 IN;IN;IN 6;87;130 15;96;139 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. P109S T125A integrase displayed nearly wild-type levels of 3' processing, DNA strand transfer, and disintegration activities, confirming that T125A is a second-site intragenic suppressor of P109S. 1996 Journal of virology Abstract HIV P109S;T125A;T125A;P109S 190;6;142;0 195;11;147;5 IN 12 21 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. Phenotypically reverted virus was detected 12 weeks after transfection with the integrase mutant carrying the P-109-->S mutation (P109S). 1996 Journal of virology Abstract HIV P109S 130 135 IN 80 89 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. Site-directed mutagenesis was used to show that the P109S T125A genotype was responsible for the P109SR replication phenotype. 1996 Journal of virology Abstract HIV P109R;P109S;P109S;T125A 97;52;97;58 103;57;103;63 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. The T125A substitution also rescued the in vitro enzyme activities of recombinant P109S integrase protein. 1996 Journal of virology Abstract HIV P109S;T125A 82;4 87;9 IN 88 97 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. Unlike the defective P109S virus, the revertant virus (designated P109SR) grew in CD4+ SupT1 cells. 1996 Journal of virology Abstract HIV P109R;P109S;P109S 66;21;66 72;26;72 8970947 Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity. We suggest that the T125A substitution restores integrase function by stabilizing a structural alteration(s) induced by the P109S mutation. 1996 Journal of virology Abstract HIV P109S;T125A 124;20 129;25 IN 48 57 8977101 The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant. The only previously available crystal structure, the F185K mutant of this domain, lacks one of the catalytically important residues, E152, located in a stretch of 12 disordered residues [Dyda et al. 1996 FEBS letters Abstract HIV F185K 53 58 8977101 The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant. We solved the structure and traced the complete active site of the catalytic domain of the human immunodeficiency virus type 1 integrase (HIV-1 IN) with the F185H mutation. 1996 FEBS letters Abstract HIV F185H 157 162 IN;IN 127;144 136;146 8986758 Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding. Crystallographic and thermodynamic analysis showed minimal structural alterations in the F43V and G47S mutant proteins, which have solvent-exposed mutant side chains. 1996 Proc Natl Acad Sci U S A Abstract HIV F43V;G47S 89;98 93;102 8986758 Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding. In contrast, some degree of disorder appears to exist in the folded state of A55F, as a result of mutating a buried side chain. 1996 Proc Natl Acad Sci U S A Abstract HIV A55F 77 81 8986758 Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding. In the present study, we produced soluble versions of three mutant CD4 molecules (F43V, G47S, and A55F) and characterized their structural properties, thermostability, and ability to bind gp120. 1996 Proc Natl Acad Sci U S A Abstract HIV A55F;F43V;G47S 98;82;88 102;86;92 gp120 188 193 8986758 Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding. Real time kinetic measurements of the interaction of the mutant proteins with gp120 showed affinity decreases of 5-fold for G47S, 50-fold for A55F, and 200-fold for F43V. 1996 Proc Natl Acad Sci U S A Abstract HIV A55F;F43V;G47S 142;165;124 146;169;128 gp120 78 83 8986758 Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding. Together, the structural and kinetic data confirm that F43V is a critical residue in gp120 recognition site, which may also include main chain interactions at residue Gly-47. 1996 Proc Natl Acad Sci U S A Abstract HIV F43V 55 59 gp120 85 90 8986949 Additional mutations detected in sequential HIV-1 isolates from ZDV-treated patients. The mutation Thr215Tyr was not observed in a case of highly resistant virus (ZDV IC50 > 6.25 microM), while the mutation Lys70Arg was found in either resistant or sensitive ones. 1997 Journal of medical virology Abstract HIV K70R;T215Y 121;13 129;22 8995604 Infectious properties of human immunodeficiency virus type 1 mutants with distinct affinities for the CD4 receptor. However, one mutation (D457R) caused a decrease in gp160 processing by approximately 80%. 1997 Journal of virology Abstract HIV D457R 23 28 gp160 51 56 8995604 Infectious properties of human immunodeficiency virus type 1 mutants with distinct affinities for the CD4 receptor. The fact that several mutations increased rates of spontaneous viral inactivation (especially D368P) suggests that HIV-1 life spans may be determined by structural stabilities of viral envelope glycoproteins. 1997 Journal of virology Abstract HIV D368P 94 99 Env 185 193 8995629 Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors. Active-site mutations V32I and I84V/A were consistently observed in the protease of highly resistant viruses, along with up to six other mutations. 1997 Journal of virology Abstract HIV I84A;I84V;V32I 31;31;22 37;37;26 PR 72 80 8995629 Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors. Despite these observations, however, most mutations had little effect on viral replication except when the active-site mutations V32I and I84V/A were coexpressed in the protease. 1997 Journal of virology Abstract HIV I84A;I84V;V32I 138;138;129 144;144;133 PR 169 177 8995629 Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors. Furthermore, the double nucleotide mutation I84A rapidly reverted to I84V upon drug removal, confirming its impact on viral fitness. 1997 Journal of virology Abstract HIV I84A;I84V 44;69 48;73 9000632 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. Apparently the Tyr181 --> Cys mutation eliminates favorable contacts of the aromatic ring of the tyrosine and the bou. 1996 Journal of molecular biology Abstract HIV Y181C 15 29 9000632 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. Mutant HIV-1 RT, containing Cys in place of Tyr at position 181 (Tyrl81Cys), is highly resistant to many NNRTIs and HIV-1 variants containing this mutation have been selected in both cell culture and clinical trials. 1996 Journal of molecular biology Abstract HIV Y181C 28 63 NNRTI;RT 105;13 111;15 9000632 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. Some positional changes in the polypeptide backbone of the beta6-beta10-beta9 sheet containing residue 181 are observed when the Tyr181Cys and wild-type complexes are compared, particularlty near residue Val179 of beta9. 1996 Journal of molecular biology Abstract HIV Y181C 129 138 9000632 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. When the structure of the Tyr181Cys mutant HIV-1 RT in complex with 8-Cl TIBO is compared with the corresponding structure containing wild-type HIV-1 RT, the overall conformations of Tyr181Cys and wild-type HIV-1 RT and of the 8-Cl TIBO inhibitors are very similar. 1996 Journal of molecular biology Abstract HIV Y181C;Y181C 26;183 35;192 RT;RT;RT 49;150;213 51;152;215 9021052 The role of genotypic heterogeneity in wild type virus populations on the selection of nonnucleoside reverse transcriptase inhibitor-resistant viruses. Resistant virus populations containing the Y181C amino acid change in the reverse transcriptase were predominantly selected with each of the tested compounds. 1997 Antiviral research Abstract HIV Y181C 43 48 RT 74 95 9030390 Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase. CONCLUSIONS: Resistance to 3TC developed in virtually all subjects treated with this drug, and was associated with the appearance of an M184V mutation in HIV reverse transcriptase. 1996 AIDS (London, England) Abstract HIV M184V 136 141 RT 158 179 9030390 Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase. OBJECTIVE: To measure the extent of HIV resistance to (-)-2',3'-dideoxy-3'-thiacytidine (3TC, lamivudine) within the context of monotherapy and to assess the presence of the M184V substitution in the case of 3TC-resistant viruses. 1996 AIDS (London, England) Abstract HIV M184V 174 179 9030390 Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase. Whether the success of 3TC in clinical trials could be due, in part, to an increase in the fidelity of HIV reverse transcriptase conferred by the M184V substitution was also considered. 1996 AIDS (London, England) Abstract HIV M184V 146 151 RT 107 128 9033399 Comparative enzymatic study of HIV-1 reverse transcriptase resistant to 2',3'-dideoxynucleotide analogs using the single-nucleotide incorporation assay. Determination of the Ki values toward 5'-triphosphates (TP) of various ddNs [3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (D4T), 2',3'-dideoxycytidine (ddC), (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (FddC), 2',3'-dideoxyadenosine (ddA), and 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA)] and 9-(2-phosphonylmethoxyethyl)adenine diphosphate (PMEApp) revealed that RTA62V/V75I/F77L/F116Y/Q151M was insensitive to ddATP, AZTTP, D4TTP, FddATP, and ddCTP, but was sensitive to PMEApp, 3TCTP, and FddCTP. 1997 Biochemistry Abstract HIV A62V;F116Y;F77L;Q151M;V75I 446;461;456;467;451 450;466;460;472;455 RT 444 446 9033399 Comparative enzymatic study of HIV-1 reverse transcriptase resistant to 2',3'-dideoxynucleotide analogs using the single-nucleotide incorporation assay. Employing the single-nucleotide incorporation assay using a heteropolymeric RNA template and DNA primers, we defined enzymatic profiles of recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing a set of five mutations [A62V, V75I, F77L, F116Y, and Q151M] which confers resistance to multiple 2',3'-dideoxynucleosides (ddNs) on HIV-1. 1997 Biochemistry Abstract HIV A62V;F116Y;F77L;Q151M;V75I 258;276;270;287;264 262;281;274;292;268 RT;RT 195;218 216;220 9048541 Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors. Finally, compensatory shifts in the I84V and V82F/ I84V complexes pick up a small number of new contacts, but too few to offset the initial loss of interactions caused by the mutations. 1997 Biochemistry Abstract HIV I84V;I84V;V82F 36;51;45 40;55;49 9048541 Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors. The Ki values of the single mutants are not additive because the side chain of Phe82 rotates out of the S1 subsite in the double mutant (the chi 1 angles of Phe82 and -182 in the V82F and V82F/I84V mutants differ by 90 and 185 degrees, respectively), further reducing the vdw interactions. 1997 Biochemistry Abstract HIV I84V;V82F;V82F 193;179;188 197;183;192 9048541 Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors. The loss of the CD1 atom of Ile84, in the I84V mutant complexes, creates a hole in the S1 subsite, reducing the number of vdw contacts and increasing the Ki values. 1997 Biochemistry Abstract HIV I84V 42 46 9048541 Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors. The V82F mutant binds DMP323 more tightly than wild type because the side chain of Phe82 forms additional vdw and edge-to-face interactions with the P1 group of DMP323. 1997 Biochemistry Abstract HIV V82F 4 8 9048541 Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors. To gain an understanding of how these two residues modulate inhibitor binding, we have measured the Ki values of three recombinant mutant proteases, I84V, V82F, and V82F/I84V, for DMP323 and DMP450, and determined the three-dimensional structures of their complexes to 2.1-1.9 A resolution with R factors of 18.7-19.6%. 1997 Biochemistry Abstract HIV I84V;I84V;V82F;V82F 170;149;155;165 174;153;159;169 PR 138 147 9052722 HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine. After treatment with DLV and ddI alone, isolates from five of seven patients developed Y181C, four in combination with K103N. 1997 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV K103N;Y181C 119;87 124;92 9052722 HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine. Previous studies have shown that the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase mutation Y181C, which confers high-level resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), develops rarely during therapy with NNRTIs plus zidovudine. 1997 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV Y181C 112 117 NNRTI;RT;NNRTI;NNRTI 158;81;206;251 193;102;212;257 9052722 HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine. Thus, in this group of nucleoside-experienced patients, combination therapy with DLV/ddI did not prevent the emergence of Y181C. 1997 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV Y181C 122 127 9052722 HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine. To determine whether didanosine (ddI) is also effective in preventing the emergence of Y181C, we analyzed delavirdine (DLV) susceptibilties and reverse transcriptase sequences of isolates obtained from patients enrolled in a pharmacokinetic study of DLV and ddI. 1997 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV Y181C 87 92 RT 144 165 9055985 A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A. In contrast, SC-52151-resistant variants selected from the monocytotropic strain SF162 had multiple substitutions in the protease gene (I11V, M461, F53L, A71V, and N88D), and the N88D mutation, re-created by oligonucleotide-mediated site-directed mutagenesis in HXB2, did not confer resistance to SC-52151. 1997 Antimicrobial agents and chemotherapy Abstract HIV A71V;F53L;I11V;N88D;N88D 154;148;136;164;179 158;152;140;168;183 PR 121 129 9055985 A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A. Passaging of virus first in SC-55389A alone and then in combination with SC-52151 resulted in the accumulation of more mutations in the protease gene (L10F, D35E, D37M, I47V, 154L, A71V, V82I, and S88D) and in the selection of a variant that was cross-resistant to multiple protease inhibitors. 1997 Antimicrobial agents and chemotherapy Abstract HIV A71V;D35E;D37M;I47V;L10F;S88D;V82I 181;157;163;169;151;197;187 185;161;167;173;155;201;191 PR;PR 136;274 144;282 9055985 A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A. Resistant isolates from both strains consistently had a mutation to serine for asparagine at amino acid 88 (N88S) in the protease gene either alone or in combination with a change to phenylalanine at position 10. 1997 Antimicrobial agents and chemotherapy Abstract HIV N88S;N88S 108;68 112;106 PR 121 129 9055985 A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A. The N88S mutation, recreated by oligonucleotide-mediated site-directed mutagenesis in HXB2, was sufficient to confer resistance to SC-55389A. 1997 Antimicrobial agents and chemotherapy Abstract HIV N88S 4 8 9055985 A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A. The potencies of L735,524 and Ro31-8959 were not reduced when these compounds were assayed against variants with either the N88S or N88D substitution. 1997 Antimicrobial agents and chemotherapy Abstract HIV N88D;N88S 132;124 136;128 9060708 Initial appearance of the 184Ile variant in lamivudine-treated patients is caused by the mutational bias of human immunodeficiency virus type 1 reverse transcriptase. The 184Ile (ATA) variant appears first, but subsequently the 184Val (GTG) variant outcompetes the 184Ile variant. 1997 Journal of virology Abstract HIV T184I 2 10 9079681 Probing structure/function relationships of HIV-1 reverse transcriptase with styrene oxide N2-guanine adducts. In addition, mutants of the polymerase in alpha-helix H (W266A and G262A) alter the termination probabilities caused by these DNA adducts, suggesting that alpha-helix H is a sensitive monitor of modifications in the minor groove of newly synthesized template-primer DNA several bases distal to the 3'-OH. 1997 The Journal of biological chemistry Abstract HIV G262A;W266A 67;57 72;63 Pol 28 38 9087484 Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Both an MT-2 cell-based culture assay and a cell-free virion-associated RT inhibition assay showed that viruses possessing an L74V and/or M184V mutation or a K65R mutation had reduced sensitivity to ddI. 1997 Antimicrobial agents and chemotherapy Abstract HIV K65R;L74V;M184V 158;126;138 162;130;143 RT 72 74 9087484 Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Other amino acid substitutions were found, but only S68G and L210W occurred in more than one patient. 1997 Antimicrobial agents and chemotherapy Abstract HIV L210W;S68G 61;52 66;56 9087484 Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Population-based sequencing of plasma virus showed that 12 of 23 (52%) patients developed known ddI resistance mutations: L74V (7 patients), K65R (2 patients), L74V with M184V (3 patients), and L74V with K65R (1 patient). 1997 Antimicrobial agents and chemotherapy Abstract HIV K65R;K65R;L74V;L74V;L74V;M184V 141;204;122;160;194;170 145;208;126;164;198;175 9087499 Highly potent oxathiin carboxanilide derivatives with efficacy against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus isolates. As a group, the UC compounds were found to be less active against viruses with the L100I, K103N, and Y181C amino acid changes in the RT and, upon in vitro selection, yielded resistant virus with the Y181C mutation in the RT. 1997 Antimicrobial agents and chemotherapy Abstract HIV K103N;L100I;Y181C;Y181C 90;83;101;199 95;88;106;204 RT;RT 133;221 135;223 9094622 Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase. Mutants carrying Gln or Ala for Glu-92 displayed wild-type activities, but substituting Lys for Glu-92 reduced in vitro 3' processing and DNA strand transfer activities 5- to 10-fold and yielded a replication-defective IN active-site mutant viral phenotype. 1997 Journal of virology Abstract HIV E92K 88 102 IN 219 221 9094622 Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase. Substituting Glu for Gln-62 reduced in vitro 3' processing and DNA strand transfer activities 5- to 10-fold without grossly affecting viral replication kinetics, suggesting that HIV-1 can replicate in T-cell lines with less than the wild-type level of IN activity. 1997 Journal of virology Abstract HIV Q62E 13 27 IN 252 254 9108091 Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor. These interactions rationalize observed resistance mutations, notably Pro-236-Leu, which occurs characteristically for BHAPs. 1997 Proc Natl Acad Sci U S A Abstract HIV P236L 70 81 9108685 Spectroscopic investigations of HIV-1 trans-activator and related peptides in aqueous solutions. HIV-1 Tat proteins (wild type and Thr40Lys mutant) and the HIV-1 Tat peptide fragments Tat(32-48) and Tat(32-72) were chemically synthesized. 1997 Biophysical chemistry Abstract HIV T40K 34 42 Tat;Tat;Tat;Tat 6;65;87;102 9;68;90;105 9108685 Spectroscopic investigations of HIV-1 trans-activator and related peptides in aqueous solutions. In fluorescence quenching studies of the full-length Tat protein (Thr40Lys), Trp11 was found to be only partially protected against solvent accessibility. 1997 Biophysical chemistry Abstract HIV T40K 66 74 Tat 53 56 9151827 Effect of mutations in the nucleocapsid protein (NCp7) upon Pr160(gag-pol) and tRNA(Lys) incorporation into human immunodeficiency virus type 1. Cotransfection of COS cells with both P31L DNA and a plasmid coding only for unprocessed Pr160(gag-pol) resulted in the viral incorporation of Pr160(gag-pol) and the rescue of selective packaging of tRNA(Lys) into the virion. 1997 Journal of virology Abstract HIV P31L 38 42 GagPol;GagPol;PR;PR 95;149;89;143 102;156;91;145 9151827 Effect of mutations in the nucleocapsid protein (NCp7) upon Pr160(gag-pol) and tRNA(Lys) incorporation into human immunodeficiency virus type 1. Of 10 mutations tested, only 2 inhibited tRNA(Lys) incorporation: a P31L mutation in the linker region and a deletion which removed both Cys-His boxes and the linker region (deltaK14-T50). 1997 Journal of virology Abstract HIV P31L 68 72 9151827 Effect of mutations in the nucleocapsid protein (NCp7) upon Pr160(gag-pol) and tRNA(Lys) incorporation into human immunodeficiency virus type 1. The P31L mutation prevents the incorporation of Pr160(gag-pol) into the virus. 1997 Journal of virology Abstract HIV P31L 4 8 GagPol;PR 54;48 61;50 9151839 Broad spectrum of in vivo fitness of human immunodeficiency virus type 1 subpopulations differing at reverse transcriptase codons 41 and 215. All 102 clones obtained from the donor and the recipient at the different time points contained the M41L mutation, which is associated with a fourfold reduction in zidovudine sensitivity. 1997 Journal of virology Abstract HIV M41L 100 104 9153194 Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. A V2E mutant has been shown to dominantly interfere with wild-type envelope-mediated syncytium formation and virus infectivity. 1997 The Journal of biological chemistry Abstract HIV V2E 2 5 Env 67 75 9153194 Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. In SDS-polyacrylamide gel electrophoresis the WT peptide formed dimers as well as higher order oligomers, whereas the V2E mutant only formed dimers. 1997 The Journal of biological chemistry Abstract HIV V2E 118 121 9153194 Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. Moreover, the V2E mutant inhibited vesicle fusion induced by the WT peptide, probably by forming inactive heteroaggregates. 1997 The Journal of biological chemistry Abstract HIV V2E 14 17 9153194 Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. The WT, but not the V2E mutant, induced liposome aggregation, destabilization, and fusion. 1997 The Journal of biological chemistry Abstract HIV V2E 20 23 9153194 Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. To understand this phenomenon, a 33-residue peptide (wild type, WT) identical to the N-terminal segment of gp41 and its V2E mutant were synthesized, fluorescently labeled, and characterized. 1997 The Journal of biological chemistry Abstract HIV V2E 120 123 gp41 107 111 9165106 Escape mutants of HIV-1 proteinase: enzymic efficiency and susceptibility to inhibition. The K(i) values determined for one inhibitor (Ro31-8959) showed that its potency towards the V82F, L90M, I84V and G48V mutant proteinases respectively was 2-, 3-, 17- and 27-fold less than against the wild-type proteinase. 1997 Biochimica et biophysica acta Abstract HIV G48V;I84V;L90M;V82F 114;105;99;93 118;109;103;97 9165106 Escape mutants of HIV-1 proteinase: enzymic efficiency and susceptibility to inhibition. The L90M proteinase again showed only marginal changes in its susceptibility to all except one of the inhibitors examined. 1997 Biochimica et biophysica acta Abstract HIV L90M 4 8 9165106 Escape mutants of HIV-1 proteinase: enzymic efficiency and susceptibility to inhibition. The L90M proteinase showed only small changes, whereas the activity of the other mutant enzymes was compromised more severely, particularly towards substrates of the -Aromatic * Pro- and pseudo-symmetrical types. 1997 Biochimica et biophysica acta Abstract HIV L90M 4 8 9165106 Escape mutants of HIV-1 proteinase: enzymic efficiency and susceptibility to inhibition. The proteinases containing mutations of single residues (e.g., G48V, V82F, I84V and L90M) were purified and their catalytic efficiencies relative to that of wild-type proteinase were examined using a polyprotein (recombinant HIV-1 gag) substrate and several series of synthetic peptides based on the -Hydrophobic * Hydrophobic-, -Aromatic * Pro- and pseudo-symmetrical types of cleavage junction. 1997 Biochimica et biophysica acta Abstract HIV G48V;I84V;L90M;V82F 63;75;84;69 67;79;88;73 Gag 231 234 9171288 Analysis of HIV-2 RT mutants provides evidence that resistance of HIV-1 RT and HIV-2 RT to nucleoside analogs involves a repositioning of the template-primer. Analysis of the behavior of HIV-2 RT mutants (Leu74Val, Glu89Gly, Ser215Tyr, Leu74Val/Ser215Tyr and Glu89Gly/Ser215Tyr) in vitro confirms the results obtained with HIV-1 RT: resistance is a function of the length of the template overhang. 1997 Journal of molecular biology Abstract HIV E89G;E89G;E89S;E89Y;L74S;L74V;L74V;L74Y;S215Y;S215Y;S215Y 56;100;100;100;77;46;77;77;86;109;66 64;108;108;108;85;54;85;85;95;118;75 RT;RT 34;170 36;172 9171288 Analysis of HIV-2 RT mutants provides evidence that resistance of HIV-1 RT and HIV-2 RT to nucleoside analogs involves a repositioning of the template-primer. These analyses also suggest that the homolog in HIV-2 RT of one of the mutations that confers resistance to AZT in HIV-1 RT (Thr215Tyr) confers resistance by repositioning of the template-primer. 1997 Journal of molecular biology Abstract HIV T215Y 125 134 RT;RT 54;121 56;123 9174190 In vitro induction of human immunodeficiency virus type 1 variants resistant to 2'-beta-Fluoro-2',3'-dideoxyadenosine. Drug sensitivity assays using recombinant infectious clones confirmed that P119S was directly responsible for the reduced sensitivity of HIV-1 to F-ddA. 1997 Antimicrobial agents and chemotherapy Abstract HIV P119S 75 80 9174190 In vitro induction of human immunodeficiency virus type 1 variants resistant to 2'-beta-Fluoro-2',3'-dideoxyadenosine. Sequence analyses of the passage 18 virus revealed changes in three amino acids in the reverse transcriptase (RT)-encoding region of the pol gene: P to S at codon 119 (P119S; present in 3 of 13 and 28 of 28 molecular clones before and after F-ddA exposure, respectively), V179D (0 of 13 and 9 of 28, respectively), and L214F (9 of 13 and 28 of 28, respectively). 1997 Antimicrobial agents and chemotherapy Abstract HIV L214F;P119S;V179D 319;168;272 324;173;277 RT;Pol;RT 87;137;110 108;140;112 9184138 Structure-based thermodynamic analysis of HIV-1 protease inhibitors. Furthermore, the formalism correctly predicts the observed change in inhibition constant for the complex of A77003 and the resistant protease mutant V82A, for which the high-resolution structure is also available. 1997 Biochemistry Abstract HIV V82A 149 153 PR 133 141 9188646 Subunit-specific mutagenesis of the cysteine 280 residue of the reverse transcriptase of human immunodeficiency virus type 1: effects on sensitivity to a specific inhibitor of the RNase H activity. The cysteine residue at position 280 (C280) is the target for NEM; HIV-1 RT carrying the mutation C280S is resistant to NEM. 1997 Journal of virology Abstract HIV C280S 98 103 RT 73 75 9197980 Synthesis and evaluation of new Reissert analogs as HIV-1 RT inhibitors. 2. Benzo[f]quinoline and pyridine derivatives. The most active products against HIV-1 RT wild type are the ethyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2b, propyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2c, and 2-cyano-1-(2'-furoyl)-1,2-dihydrobenzo[f]quinoline 2n, which maintain their activity against the mutant type P236L, resulting inactive against the Y181C type. 1997 Drug design and discovery Abstract HIV P236L;Y181C 296;334 301;339 RT 39 41 9197981 Synthesis and evaluation of new Reissert analogs as HIV-1 reverse transcriptase inhibitors. 1. Quinoline and quinoxaline derivatives. These compounds are active against the HIV-1 RT mutant type P236L (2f, IC50 = 1.2 microM) and present activity as anti-infective agents in HLT41acZ-1IIIB cells, showing no cytotoxicity at the active concentrations. 1997 Drug design and discovery Abstract HIV P236L 60 65 RT 45 47 9209307 Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. Second, recombinant HIV, that contained the M184V substitution in RT, could not replicate in the presence of d4T, AZT, Nevirapine, Delavirdine or Saquinavir, using previously described protocols for the generation of drug resistance in vitro. 1997 Leukemia Abstract HIV M184V 44 49 RT 66 68 9209307 Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. This apparent contradiction is explained by an increase in the fidelity of the HIV RT, conferred by the M184V mutation, on the basis of the following observations. 1997 Leukemia Abstract HIV M184V 104 109 RT 83 85 9209307 Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. This suggests that increased fidelity of M184V RT may limit variability in the HIV env gene and result in protracted effectiveness of anti-viral immune responsiveness. 1997 Leukemia Abstract HIV M184V 41 46 Env;RT 83;47 86;49 9209307 Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. This was in spite of high-level resistance to this compound and the appearance of the M184V substitution in the HIV reverse transcriptase (RT) gene, responsible for diminished sensitivity to 3TC. 1997 Leukemia Abstract HIV M184V 86 91 RT;RT 116;139 137;141 9209308 Cross-resistance analysis and molecular modeling of nonnucleoside reverse transcriptase inhibitors targeting drug-resistance mutations in the reverse transcriptase of human immunodeficiency virus. Since Y181C and L1001 are the most commonly observed resistance-engendering mutations, RT enzymatic analysis was correlated with molecular modeling to glean information on the structural interactions between these NNRTIs and RT. 1997 Leukemia Abstract HIV Y181C 6 11 NNRTI;RT;RT 214;87;225 220;89;227 9211905 Kinetic analysis of four HIV-1 reverse transcriptase enzymes mutated in the primer grip region of p66. Implications for DNA synthesis and dimerization. However, the affinity for primer-template DNA was reduced 27-fold for mutant p66(W229A)/51 and 23-fold for mutant p66(G231A)/51, and the maximal pre-steady-state rate of nucleotide incorporation, kpol, was reduced 27-fold for p66(W229A)/51 and 70-fold for p66(G231A)/51, respectively. 1997 The Journal of biological chemistry Abstract HIV G231A;G231A;W229A;W229A 118;260;81;230 123;265;86;235 9211905 Kinetic analysis of four HIV-1 reverse transcriptase enzymes mutated in the primer grip region of p66. Implications for DNA synthesis and dimerization. Mutant p66(M230A)/51 revealed no reduced affinity for primer-template but showed a 71-fold reduced affinity for dTTP. 1997 The Journal of biological chemistry Abstract HIV M230A 11 16 9211905 Kinetic analysis of four HIV-1 reverse transcriptase enzymes mutated in the primer grip region of p66. Implications for DNA synthesis and dimerization. Mutation of Y232A showed the smallest effect on polymerase function. 1997 The Journal of biological chemistry Abstract HIV Y232A 12 17 Pol 48 58 9222047 Emergence of resistant variants of HIV in vivo during monotherapy with the proteinase inhibitor saquinavir. Hence, in vivo, the Leu90-->Met but not the Gly48-->Val mutation is necessary, but not sufficient, for phenotypic resistance to saquinavir in HIV. 1997 The Journal of antimicrobial chemotherapy Abstract HIV G48V;L90M 44;20 55;31 9222047 Emergence of resistant variants of HIV in vivo during monotherapy with the proteinase inhibitor saquinavir. In no patient was a Gly48-->Val mutation observed, although this has been associated with resistance in vitro. 1997 The Journal of antimicrobial chemotherapy Abstract HIV G48V 20 31 9222047 Emergence of resistant variants of HIV in vivo during monotherapy with the proteinase inhibitor saquinavir. The Leu90-->Met mutation was observed in five subjects, but a greater than eight-fold phenotypic change in antiviral susceptibility was seen in only two of these. 1997 The Journal of antimicrobial chemotherapy Abstract HIV L90M 4 15 9224818 Development of resistance of human immunodeficiency virus type 1 to dextran sulfate associated with the emergence of specific mutations in the envelope gp120 glycoprotein. The following mutations were found in the gp120 molecule of the DS-resistant HIV-1 strain but not in the wild-type strain: S114N in the V1 loop region; S134N in the V2 loop region; K269E, Q278H, and N293D in the V3 loop region; N323S in the C3 region; a deletion of five amino acids (Phe-Asn-Ser-Thr-Trp) at positions 364-368 in the V4 loop; and R3871 in the CD4 binding domain. 1997 Molecular pharmacology Abstract HIV K269E;N293D;N323S;Q278H;S114N;S134N 181;199;228;188;123;152 186;204;233;193;128;157 gp120 42 47 9235945 Transduction of activation signal that follows HIV-1 binding to CD4 and CD4 dimerization involves the immunoglobulin CDR3-like region in domain 1 of CD4. E91K, E92K, and E87K,D88K mutant CD4 molecules were unable to bind a CD4 synthetic aromatically modified exocyclic, CDR3.AME-(82-89), that mimics the CDR3-like loop structure and binds to native cell surface CD4. 1997 The Journal of biological chemistry Abstract HIV D88K;E87K;E92K;E91K 21;16;6;0 25;22;10;4 9235945 Transduction of activation signal that follows HIV-1 binding to CD4 and CD4 dimerization involves the immunoglobulin CDR3-like region in domain 1 of CD4. Moreover, A2.01-3B cells expressing the E91K,E92K mutant exhibited a lower HIV-1Lai replication. 1997 The Journal of biological chemistry Abstract HIV E91K;E92K 40;45 46;49 9235945 Transduction of activation signal that follows HIV-1 binding to CD4 and CD4 dimerization involves the immunoglobulin CDR3-like region in domain 1 of CD4. Substitutions of negatively charged residues by positively charged residues within the CDR3-like loop either inhibited NF-kappaB translocation after HIV-1 and gp120-anti-gp120 immune complexes binding to E91K,E92K mutants or induced its constitutive activation for E87K,D88K mutants. 1997 The Journal of biological chemistry Abstract HIV D88K;E87K;E87K;E91K;E92K 270;265;265;204;209 274;269;271;210;213 gp120;gp120 159;170 164;175 9237704 Lamivudine-resistant human immunodeficiency virus type 1 variants (184V) require multiple amino acid changes to become co-resistant to zidovudine in vivo. Exposure of human immunodeficiency virus to the nucleoside analogue lamivudine (3TC) rapidly selects for resistant variants with a valine at codon 184 (M184V) in the catalytic site of reverse transcriptase. 1997 The Journal of infectious diseases Abstract HIV M184V 152 157 RT 184 205 9254628 Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC. The affinity of 3-TCTP to the RT-3TC-primer/template complex was not affected by the mutation M184V. 1997 Biochemistry Abstract HIV M184V 94 99 RT 30 32 9254628 Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC. Two mutants of HIV-1 reverse transcriptase (RT) associated with high-level resistance of the virus to AZT (RT-AZT: D67N, K70R, T215Y, K219Q, and M41L) or 3-TC (RT-3TC: M184V) were expressed in Escherichia coli and purified. 1997 Biochemistry Abstract HIV D67N;K219Q;K70R;M184V;M41L;T215Y 115;134;121;168;145;127 119;139;125;173;149;132 RT;RT;RT;RT 21;44;107;160 42;46;109;162 9258355 Synthesis and in vitro activity of long-chain 5'-O-[(alkoxycarbonyl)phosphinyl]-3'-azido-3'-deoxythymidines against wild-type and AZT- and foscarnet-resistant strains of HIV-1. In assays against E89K, 9a-c had mean EC50 values of 0.13, 0.009, and 0.17 microM, whereas the EC50 of PFA was > 1000 microM and that of AZT was 0.009 microM; thus, E89K was highly resistant to PFA but not cross-resistant to either AZT or the lipophilic PFA-AZT conjugates. 1997 Journal of medicinal chemistry Abstract HIV E89K;E89K 18;165 22;169 9258355 Synthesis and in vitro activity of long-chain 5'-O-[(alkoxycarbonyl)phosphinyl]-3'-azido-3'-deoxythymidines against wild-type and AZT- and foscarnet-resistant strains of HIV-1. Lipophilic esters of 3'-azido-3'-deoxy-5'-O-(carboxyphosphinyl)thymidine (PFA-AZT) were synthesized and tested for antiretroviral activity in CD4+ HT4-6C cells infected with either wild-type HIV-1LAI, a PFA-resistant strain encoding a single-point mutation in reverse transcriptase (E89K), or an AZT-resistant clinical isolate (A018-post). 1997 Journal of medicinal chemistry Abstract HIV E89K 283 287 RT 260 281 9261348 Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). Finally, sequence analysis of U5 and PBS regions of proviruses from pHXB2(His-AC-GAC) with wild-type RT revealed considerably more nucleotide substitutions than in viruses derived from pHXB2(His-AC-GAC) containing the M184V mutation in RT after extended in vitro culture. 1997 Journal of virology Abstract HIV M184V 218 223 RT;RT 101;236 103;238 9261348 Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). The initiation of reverse transcription was delayed in viruses derived from pHXB2(His-AC-TGT) with wild-type RT and M184V RT compared to viruses derived from pHXB2(His-AC-GAC). 1997 Journal of virology Abstract HIV M184V 116 121 RT;RT;RT 18;109;122 39;111;124 9261348 Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). The M184V RT mutation was cloned into pHXB2(His-AC-GAC) and pHXB2(His-AC-TGT). 1997 Journal of virology Abstract HIV M184V 4 9 RT 10 12 9261348 Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). To further address this possibility, we used a specific mutation in reverse transcriptase (RT), a methionine-to-valine change in the highly conserved YMDD amino acid motif of HIV-1 RT (M184V), which has been shown in previous studies to influence the fidelity and activity of the enzyme. 1997 Journal of virology Abstract HIV M184V 185 190 RT;RT;RT 68;91;181 89;93;183 9261348 Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). Using an endogenous reverse transcription-PCR assay to analyze the reverse transcription of viruses obtained after transfection, we found that viruses derived from pHXB2(His-AC-GAC) with the wildtype RT were slightly faster in the initiation of reverse transcription than viruses with M184V RT. 1997 Journal of virology Abstract HIV M184V 285 290 RT;RT;RT;RT;RT 20;67;245;200;291 41;88;266;202;293 9261348 Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). Virus derived from pHXB2(His-AC-GAC) with M184V RT had slightly delayed replication compared to the virus from pHXB2(His-AC-GAC) with wild-type RT; in contrast, virus from pHXB2(His-AC-TGT) with M184V RT was severely compromised in replication. 1997 Journal of virology Abstract HIV M184V;M184V 42;195 47;200 RT;RT;RT 48;144;201 50;146;203 9261351 Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr. In contrast, mutation of Leu68 to Ser resulted in a protein that localizes in the cytoplasm while retaining the ability to arrest host cell proliferation. 1997 Journal of virology Abstract HIV L68S 25 37 9261351 Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr. Interestingly, we found that two Vpr mutants harboring single amino acid substitutions (A30L and G75A) retained the ability to translocate to the nucleus but were impaired in the cell cycle arrest function. 1997 Journal of virology Abstract HIV A30L;G75A 88;97 93;101 Vpr 33 36 9261388 Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites. Similarly, rates of replication of viruses with mutations M46L/I, I54V, and V82A in protease were enhanced both in the presence and in the absence of Indinavir when combined with mutations in the gag p7/p1 and the gag p1/p6 cleavage sites. 1997 Journal of virology Abstract HIV I54V;M46I;M46L;V82A 66;58;58;76 70;64;64;80 PR;Gag;Gag;Gag 84;196;214;221 92;199;217;223 9299620 Population dynamics studies of wild-type and drug-resistant mutant HIV in mixed infections. Utilizing this system we studied the fate of mixtures of wild-type and the protease-resistant mutant variant I84V in the presence and absence of the cyclic urea HIV protease inhibitor, DMP 450. 1997 Virology Abstract HIV I84V 109 113 PR;PR 75;165 83;173 9299620 Population dynamics studies of wild-type and drug-resistant mutant HIV in mixed infections. We also examined the dynamics of mixtures of wild-type and the resistant mutant variant, L100I, in the presence and absence of the drug DMP 266. 1997 Virology Abstract HIV L100I 89 94 9315877 Kinetic properties of saquinavir-resistant mutants of human immunodeficiency virus type 1 protease and their implications in drug resistance in vivo. Although the protease activity of G48V, L90M, and G48V/L90M are only about 10, 7, and 3% of that of the wild-type HIV-1 protease in the absence of inhibitor, the resistance tendencies of the three mutants are clearly manifest by relatively less activity loss as inhibitor concentration becomes higher. 1997 Biochemistry Abstract HIV G48V;G48V;L90M;L90M 34;50;40;55 38;54;44;59 PR;PR 13;120 21;128 9315877 Kinetic properties of saquinavir-resistant mutants of human immunodeficiency virus type 1 protease and their implications in drug resistance in vivo. In order to study the basis of resistance of human immunodeficiency virus, type 1 (HIV-1), to HIV-1 protease inhibitor saquinavir, the catalytic and inhibition properties of the wild-type HIV-1 protease and three saquinavir resistant mutants, G48V, L90M, and G48V/L90M, were compared. 1997 Biochemistry Abstract HIV G48V;G48V;L90M;L90M 243;259;264;249 247;263;268;253 PR;PR 100;194 108;202 9325327 Thioltransferase (glutaredoxin) is detected within HIV-1 and can regulate the activity of glutathionylated HIV-1 protease in vitro. Here, we examined diglutathionylated wild type protease (Cys-67-SSG, Cys-95-SSG) and the monoglutathionylated protease mutants (C67A, Cys-95-SSG and C95A, Cys-67-SSG) as potential substrates for thioltransferase (glutaredoxin). 1997 The Journal of biological chemistry Abstract HIV C67A;C95A 128;149 132;153 PR;PR 47;110 55;118 9343170 Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. A novel mutation, Pro225His, consistently appeared in a Val106Ala RT-mutated genetic background. 1997 Journal of virology Abstract HIV P225H;V106A 18;56 27;65 RT 66 68 9343170 Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. Interestingly, site-directed mutagenesis studies revealed that the Pro225His-mutated RT had acquired markedly greater sensitivity to bis(heteroaryl)piperazine (BHAP U-90152) (delavirdine) but not to any of the other NNRTIs. 1997 Journal of virology Abstract HIV P225A;P225D;P225Delta;P225E;P225H;P225M;P225T;P225U 67;67;67;67;67;67;67;67 76;76;76;76;76;76;76;76 NNRTI;RT 216;85 222;87 9343170 Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. The contribution of this mutation to the resistance of the mutant HIV-1 RT to NNRTIs was additive to the resistance caused by the Val106Ala mutation. 1997 Journal of virology Abstract HIV V106A 130 139 NNRTI;RT 78;72 84;74 9343170 Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1. The kinetics of inhibition of the Pro225His mutant RT by the NNRTIs (including BHAP U-90152) was not substantially different from that observed for the wild-type RT. 1997 Journal of virology Abstract HIV P225H 34 43 NNRTI;RT;RT 61;51;162 67;53;164 9343174 Resistance to a drug blocking human immunodeficiency virus type 1 entry (RPR103611) is conferred by mutations in gp41. In the context of LAI gp41, the I84S substitution was sufficient for drug resistance. 1997 Journal of virology Abstract HIV I84S 32 36 gp41 22 26 9343174 Resistance to a drug blocking human immunodeficiency virus type 1 entry (RPR103611) is conferred by mutations in gp41. Its product differed from the parental sequence at two positions in gp41, with changes of arginine 22 to alanine (R22A) and isoleucine 84 to serine (I84S), the gp120 being identical. 1997 Journal of virology Abstract HIV I84S;I84S;R22A;R22A 149;124;114;90 153;147;118;112 gp120;gp41 160;68 165;72 9343245 Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. In a series of experiments, we have shown that (i) a cloned virus with an engineered Leu74Val mutation in RT was attenuated for replication; (ii) a Val-to-Leu revertant of Leu74Val in the pNL4-3 background replicated with an efficiency similar to that of the wild-type virus; (iii) when two isolates from the same patient were compared, a clinical isolate containing mutations Leu74Val and Thr215Tyr was attenuated for replication compared to one in which the Thr215Tyr mutation alone was present; and (iv) the viruses with the Leu74Val mutation showed an 11% loss of fitness in a single passage compared to the wild-type and a mutant virus containing a Lys70Arg mutation. 1997 Journal of virology Abstract HIV K70R;L74V;L74V;L74V;L74V;T215Y;T215Y 654;85;172;377;528;390;460 662;93;180;385;536;399;469 RT 106 108 9343245 Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. In this report, we provide evidence that the ddI-associated Leu74Val mutation confers a replication disadvantage to the virus. 1997 Journal of virology Abstract HIV L74V 60 68 9343245 Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. The decreased replication ability of the Leu74Val mutant virus selected by ddI therapy provides a strong rationale for the lower viral RNA levels observed with ddI therapy compared to zidovudine therapy in clinical trials. 1997 Journal of virology Abstract HIV L74V 41 49 9343245 Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. The Leu-74 to Val (Leu74Val) mutation in human immunodeficiency virus type 1 reverse transcriptase (RT) develops as a consequence of didanosine (ddI) therapy and is associated with a decreased susceptibility to ddI. 1997 Journal of virology Abstract HIV L74V;L74V 19;4 27;17 RT;RT 77;100 98;102 9343245 Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. The loss of fitness for viruses grown in drug-free medium could result in an inability to detect a Leu74Val mutant in clinical isolates obtained post-ddI therapy. 1997 Journal of virology Abstract HIV L74V 99 107 9343254 Susceptibility of human immunodeficiency virus type 1 group O isolates to antiretroviral agents: in vitro phenotypic and genotypic analyses. Phylogenetic analysis of the pol gene showed that these isolates formed a separate cluster within group O, and genotypic analysis revealed a tyrosine-to-cysteine substitution at residue 181. 1997 Journal of virology Abstract HIV Y181C 141 189 Pol 29 32 9358162 Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. Fidelity differences between M184V and wild-type RT were most marked in extension of A:G (49-fold) and A:C (16-fold) mispairs, with only a marginal (3-fold) decrease in the extension of A:A mispairs. 1997 Nucleic acids research Abstract HIV M184V 29 34 RT 49 51 9358162 Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. It was of interest to determine the fidelity of RNA-dependent DNA polymerization (RDDP) of M184V RT compared with wild-type because this step occurs first in reverse transcription; errors made during this step may be copied in subsequent polymerization steps. 1997 Nucleic acids research Abstract HIV M184V 91 96 RT;RT 158;97 179;99 9358162 Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. RT containing a methionine to isoleucine (M184I) mutation showed only slight increases in RDDP fidelity compared with wild-type, ranging from 1.5- to 6-fold increases. 1997 Nucleic acids research Abstract HIV M184I 42 47 RT 0 2 9358162 Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. Using an in vitro mispaired primer extension assay, M184V-mutated RT exhibited 3-49-fold decreased frequency of mispair extension compared with wild-type RT. 1997 Nucleic acids research Abstract HIV M184V 52 57 RT;RT 66;154 68;156 9358162 Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. Viruses containing the M184V substitution are highly resistant to (-)-2'-dideoxy-3'-thiacytidine (3TC) in vitro and in patients treated with 3TC monotherapy. 1997 Nucleic acids research Abstract HIV M184V 23 28 9358162 Higher fidelity of RNA-dependent DNA mispair extension by M184V drug-resistant than wild-type reverse transcriptase of human immunodeficiency virus type 1. We and others have previously found that the fidelity of DNA-dependent DNA polymerization (DDDP) of M184V-mutated HIV-1 RT is significantly higher than that of wild-type RT. 1997 Nucleic acids research Abstract HIV M184V 100 105 RT;RT 120;170 122;172 9359746 Zidovudine-resistant human immunodeficiency virus type 1 strains subcultured in the presence of both lamivudine and quinoxaline HBY 097 retain marked sensitivity to HBY 097 but not to lamivudine. Replication of zidovudine-resistant human immunodeficiency virus type 1 (HIV-1) strains (containing the 41 Met-->Leu and 215 Thr-->Tyr mutations in reverse transcriptase [RT]) was inhibited to a significantly greater extent by the combination of lamivudine and quinoxaline HBY 097 than by either drug alone or even fully suppressed by concomitant HBY 097 and lamivudine administration at relatively low concentrations. 1997 The Journal of infectious diseases Abstract HIV M41L;T215T 104;121 116;134 RT;RT 148;171 169;173 9359746 Zidovudine-resistant human immunodeficiency virus type 1 strains subcultured in the presence of both lamivudine and quinoxaline HBY 097 retain marked sensitivity to HBY 097 but not to lamivudine. The virus recovered after exposure to the drug combinations individually had acquired the 103 Lys-->Arg, 138 Glu-->Lys, 184 Met-->Ile, and 189 Val-->Ile mutations in the genetic zidovudine-resistance background of zidovudine-resistant HIV-1. 1997 The Journal of infectious diseases Abstract HIV E138K;K103R;M184I;V189I 105;90;120;139 118;103;133;152 9369478 Pre-steady-state kinetic characterization of wild type and 3'-azido-3'-deoxythymidine (AZT) resistant human immunodeficiency virus type 1 reverse transcriptase: implication of RNA directed DNA polymerization in the mechanism of AZT resistance. A detailed pre-steady-state kinetic analysis of wild type and the clinically important AZT resistant mutant (D67N, K70R, T215Y, K219Q) HIV-1 reverse transcriptase was conducted to understand the mechanistic basis of drug resistance. 1997 Biochemistry Abstract HIV D67N;K219Q;K70R;T215Y 109;128;115;121 113;133;119;126 RT 141 162 9371337 Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs. L90M had a lower Km than the wild type, whereas the G48V/L90M double mutant had an increased Km compared with that of the wild type, contributing to a 10-fold reduction in the k(cat)/Km. 1997 Antimicrobial agents and chemotherapy Abstract HIV G48V;L90M;L90M 52;57;0 56;61;4 9371337 Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs. The proteinase gene of resistant virus was sequenced, and key mutations (G48V, V82A, I84V, L90M, and G48V/L90M) were introduced into clones used for the expression, purification, and further characterization of the enzyme. 1997 Antimicrobial agents and chemotherapy Abstract HIV G48V;G48V;I84V;L90M;L90M;V82A 73;101;85;106;91;79 77;105;89;110;95;83 9371337 Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs. The resistance of the I84V mutant may be attributed to a loss of van der Waals interactions with the inhibitor, since the larger amino acid side chain involved in the interaction is replaced by a smaller side chain. 1997 Antimicrobial agents and chemotherapy Abstract HIV I84V 22 26 9371337 Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs. Virus with the same mutation is also resistant, although the double mutation L10F/I84V confers even greater resistance. 1997 Antimicrobial agents and chemotherapy Abstract HIV I84V;L10F 82;77 86;81 9371337 Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs. Vitality values were used to show that the enzyme of the I84V mutant is the enzyme most resistant to the two cyclic urea inhibitors DMP 323 and AHA 008. 1997 Antimicrobial agents and chemotherapy Abstract HIV I84V 57 61 9371564 The roles of the human immunodeficiency virus type 1 Pol protein and the primer binding site in the placement of primer tRNA(3Lys) onto viral genomic RNA. In contrast, the elimination of protease activity through a D25A (Asp-->Ala) point mutation in the protease-active site (construct BH10-PR) did cause a drop in the efficiency of tRNA(3Lys) placement. 1997 Journal of virology Abstract HIV D25A 60 64 PR;PR;Asp;PR 32;99;66;136 40;107;69;138 9371564 The roles of the human immunodeficiency virus type 1 Pol protein and the primer binding site in the placement of primer tRNA(3Lys) onto viral genomic RNA. We also generated a mutant within the polymerase-active site of RT (D185H) (Asp-->His) that eliminated RT polymerase activity. 1997 Journal of virology Abstract HIV D185H 68 73 Pol;Pol;Asp;RT;RT 38;106;76;64;103 48;116;79;66;105 9376351 Effect of RNA secondary structure on RNA cleavage catalyzed by HIV-1 reverse transcriptase. Characterization of an RNase H-deficient RT mutant (D443N) shows that RNase H activity is not critical for RT to read through the RNA secondary structure. 1997 Biochemistry Abstract HIV D443N 52 57 RT;RT 41;107 43;109 9398161 Role of glutamine-151 of human immunodeficiency virus type-1 reverse transcriptase in RNA-directed DNA synthesis. Glutamine-151 of HIV-1 RT has been shown to be a catalytically important residue through the characterization of its mutant phenotype Glu151Ala (Sarafianos et al., 1995a). 1997 Biochemistry Abstract HIV E151A 134 143 RT 23 25 9398161 Role of glutamine-151 of human immunodeficiency virus type-1 reverse transcriptase in RNA-directed DNA synthesis. Our results with Q151A suggest that the side chain of Q151 may help stabilize the side chain of R72, and the loss of pyrophosphorolysis activity observed with the Q151 mutant may be the indirect manifestation of this stabilizing effect on R72. 1997 Biochemistry Abstract HIV Q151A 17 22 9398161 Role of glutamine-151 of human immunodeficiency virus type-1 reverse transcriptase in RNA-directed DNA synthesis. Similar properties have been previously reported for a mutant of R72 (R72A) of HIV-1 RT (Sarafianos et al., 1995b). 1997 Biochemistry Abstract HIV R72A 70 74 RT 85 87 9398161 Role of glutamine-151 of human immunodeficiency virus type-1 reverse transcriptase in RNA-directed DNA synthesis. The Q151A mutant was found to be nearly devoid of pyrophosphorolytic activity on a RNA-PBS template-primer. 1997 Biochemistry Abstract HIV Q151A 4 9 9398161 Role of glutamine-151 of human immunodeficiency virus type-1 reverse transcriptase in RNA-directed DNA synthesis. We find that Q151A mutant exhibited a severe reduction in the polymerase activity without any significant effect on the affinity for dNTP substrate. 1997 Biochemistry Abstract HIV Q151A 13 18 Pol 62 72 9405155 Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions. Determination of the rate constants for Nevirapine binding (kon) and dissociation (koff) for the mutant and wild-type enzymes showed that mutations L100I and V106A increased the koff values by 12 and 8.5-fold, respectively, without significantly affecting the kon, whereas mutation K103N decreased the kon 5-fold without increasing the koff. 1997 Journal of molecular biology Abstract HIV K103N;L100I;V106A 282;148;158 287;153;163 9405155 Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions. In addition, mutations L100I and Y181I reduced the catalytic potential of HIV-1 RT. 1997 Journal of molecular biology Abstract HIV L100I;Y181I 23;33 28;38 RT 80 82 9405155 Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions. less sensitive) Y188L < V106A < L100I < K103N < wild-type. 1997 Journal of molecular biology Abstract HIV K103N;L100I;V106A;Y188L 40;32;24;14 45;37;29;21 9405155 Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions. Mutations Y181I and Y188L, on the other hand, conferred resistance to Nevirapine affecting both koff and kon values. 1997 Journal of molecular biology Abstract HIV Y181I;Y188L 10;20 15;25 9405155 Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions. The kinetic parameters governing the inhibition by Nevirapine of the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase have been determined by steady-state kinetic analysis with the wild-type enzyme and with mutant reverse transcriptases containing the single amino acid substitutions L100I, K103N, V106A, V179D, Y181I and Y188L. 1997 Journal of molecular biology Abstract HIV K103N;L100I;V106A;V179D;Y181I;Y188L 311;304;318;325;332;342 316;309;323;330;337;347 RT;RT 116;234 137;256 9405155 Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions. While the mutant V179D was inhibited by Nevirapine as the wild-type enzyme, all the other mutations displayed a 17 to 90-fold reduced sensitivity to the drug in the order: Y181I<(i.e. 1997 Journal of molecular biology Abstract HIV V179D;Y181I 17;172 22;177 9420228 Cells with high cyclophilin A content support replication of human immunodeficiency virus type 1 Gag mutants with decreased ability to incorporate cyclophilin A. Either a point mutation in Gag (P222A) or drugs which bind CyPA decrease virion incorporation of CyPA and interfere with HIV-1 replication. 1998 Journal of virology Abstract HIV P222A 32 37 Gag 27 30 9420228 Cells with high cyclophilin A content support replication of human immunodeficiency virus type 1 Gag mutants with decreased ability to incorporate cyclophilin A. These experiments demonstrated that a higher cellular CyPA content of some cells was able to compensate for the decreased binding affinity of P222A mutant Gag for CyPA, allowing virus replication to occur. 1998 Journal of virology Abstract HIV P222A 142 147 Gag 155 158 9420228 Cells with high cyclophilin A content support replication of human immunodeficiency virus type 1 Gag mutants with decreased ability to incorporate cyclophilin A. We have found that lymphoid cells varied greatly in their CyPA content and that cells with high CyPA content supported the replication of P222A HIV-1 Gag mutants. 1998 Journal of virology Abstract HIV P222A 138 143 Gag 150 153 9425451 Inhibition of HIV-1 replication by a Tat transdominant negative mutant in human peripheral blood lymphocytes from healthy donors and HIV-1-infected patients. It was previously shown that a tat mutant (tat22) where cysteine 22 is substituted by glycine behaves as a transdominant negative mutant in Jurkat T cells lytically or latently infected by HIV-1. 1997 Gene therapy Abstract HIV C22G 56 93 Tat;Tat 31;43 34;46 9436978 HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. A mutant form of Vpr (Vpr F34I) that does not localize at the nuclear envelope, or bind to importin-alpha and nucleoporins, renders HIV-1 incapable of infecting macrophages efficiently. 1998 Genes & development Abstract HIV F34I 26 30 Env;Vpr;Vpr 70;17;22 78;20;25 9436978 HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Vpr F34I, however, still causes a G2 arrest, demonstrating that the dual functions of Vpr are genetically separable. 1998 Genes & development Abstract HIV F34I 4 8 Vpr;Vpr 0;86 3;89 9445075 Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line. Introduction of the H13-->L mutation in a wild-type tat background caused a severe reduction in transcriptional activation. 1998 Journal of virology Abstract HIV H13L 20 27 Tat 52 55 9445075 Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line. One Tat cDNA lacked an ATG initiation codon, while the other contained an H-to-L mutation at amino acid 13 (H13-->L). 1998 Journal of virology Abstract HIV H13L 108 115 Tat 4 7 9450540 Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. A model of saquinavir-resistant mutant protease G48V in complex with saquinavir predicts interactions similar to those found in the G48H crystal. 1997 FEBS letters Abstract HIV G48H;G48V 132;48 136;52 PR 39 47 9450540 Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. The crystal structure of human immunodeficiency virus type 1 (HIV-1) protease mutant G48H with peptidic inhibitor U-89360E is described. 1997 FEBS letters Abstract HIV G48H 85 89 PR 69 77 9464253 A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues. Reasons for the decrease in binding affinities with the two critical mutants (V82T/I84V and 4X) have also been elucidated in detail. 1998 Biochemical and biophysical research communications Abstract HIV I84V;V82T 83;78 87;82 9464253 A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues. Recent experimental findings with HIV-1 protease (HIV-1 PR) mutants containing variations at four residues, M46I, L63P, V82T and I84V, have shown that only mutants containing the latter two exhibit cross resistance to the inhibitors ABT-538 and VX-478. 1998 Biochemical and biophysical research communications Abstract HIV I84V;L63P;M46I;V82T 129;114;108;120 133;118;112;124 PR;PR 40;56 48;58 9464253 A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues. The V82T and I84V modifications in fact concern residues in the active site while the other two are in the flap (M46I) and hinge (L63P) domains of the enzyme. 1998 Biochemical and biophysical research communications Abstract HIV I84V;L63P;M46I;V82T 13;130;113;4 17;134;117;8 9464253 A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues. We have modelled the M46I/L63P, V82T/I84V and M46I/L63P/ V82T/I84V (4X) mutants of HIV-PR and computed their complexation energies with these two inhibitors. 1998 Biochemical and biophysical research communications Abstract HIV L63P;M46I;I84V;I84V;L63P;M46I;V82T;V82T 51;46;37;62;26;21;32;57 55;50;41;66;30;25;36;61 PR 87 89 9468363 Inactivation of a common epitope responsible for the induction of antibody-dependent enhancement of HIV. A conservative W596Y mutation blocks binding of all enhancing human MAb with retention of gp120-gp41 association. 1998 AIDS (London, England) Abstract HIV W596Y 15 20 gp120;gp41 90;96 95;100 9468363 Inactivation of a common epitope responsible for the induction of antibody-dependent enhancement of HIV. A conservative W596Y mutation completely blocked the binding of all human MAb, but had no effect on gp120-gp41 association. 1998 AIDS (London, England) Abstract HIV W596Y 15 20 gp120;gp41 100;106 105;110 9477118 HIV-1 acquires resistance to two classes of antiviral drugs through homologous recombination. Co-transfection of COS-7 cells with an HIV-1 plasmid (pSUM13) carrying five mutations in the reverse transcriptase (RT)-encoding region (A62V, V75I, F77L, F116Y, Q151M), conferring resistance to multiple dideoxynucleoside analogs (ddNs), and another HIV-1 plasmid (pSUM431) carrying five mutations in the protease-encoding region (V321, L33F, K451, 184V, L89M), conferring resistance to protease inhibitors such as KNI-272, readily produced HIV-1 carrying both sets of mutations when propagated in MT-2 cells in the presence of azidothymidine (AZT) and KNI-272. 1997 Antiviral research Abstract HIV A62V;F116Y;F77L;L33F;L89M;Q151M;V75I 137;155;149;337;355;162;143 141;160;153;341;359;167;147 RT;PR;PR;RT 93;305;387;116 114;313;395;118 9491915 Lamivudine resistance of HIV type 1 does not delay development of resistance to nonnucleoside HIV type 1-specific reverse transcriptase inhibitors as compared with wild-type HIV type 1. Our experiments showed that there was no significant delay in virus breakthrough of the M184V mutant as compared with the wild-type virus. 1998 AIDS research and human retroviruses Abstract HIV M184V 88 93 9491915 Lamivudine resistance of HIV type 1 does not delay development of resistance to nonnucleoside HIV type 1-specific reverse transcriptase inhibitors as compared with wild-type HIV type 1. The reverse transcriptase of the M184V mutant has been reported to have a higher fidelity. 1998 AIDS research and human retroviruses Abstract HIV M184V 33 38 RT 4 25 9491915 Lamivudine resistance of HIV type 1 does not delay development of resistance to nonnucleoside HIV type 1-specific reverse transcriptase inhibitors as compared with wild-type HIV type 1. We compared the development of resistance toward BI-RG-587 (nevirapine) and alpha-APA R89439 (loviride) starting from the wild-type HIV-1 strain IIIB and the 3TC-resistant HIV-1 strain containing the M184V mutation. 1998 AIDS research and human retroviruses Abstract HIV M184V 200 205 9491915 Lamivudine resistance of HIV type 1 does not delay development of resistance to nonnucleoside HIV type 1-specific reverse transcriptase inhibitors as compared with wild-type HIV type 1. We therefore conclude that the reported higher fidelity of the M184V mutant does not lead to a delay in the development of resistance to the nonnucleoside reverse transcriptase inhibitors nevirapine and loviride. 1998 AIDS research and human retroviruses Abstract HIV M184V 63 68 NNRTI 141 176 9491916 A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. On increasing drug concentrations (stepwise up to 30 microg/ml) the virus retained the V106A RT mutation but acquired the novel F227L mutation in the RT genome in addition to the L100I, K1O1I, and Y181C mutations. 1998 AIDS research and human retroviruses Abstract HIV F227L;L100I;V106A;Y181C 128;179;87;197 133;184;92;202 RT;RT 93;150 95;152 9491916 A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. Treatment of wild-type human immunodeficiency virus [HIV-1(IIIB)]-infected cell cultures with the thiocarboxanilide UC-781 under low selective pressure (i.e., 0.01 microg/ml) resulted in the emergence of V106A RT mutant virus. 1998 AIDS research and human retroviruses Abstract HIV V106A 204 209 RT 210 212 9499059 Construction and characterization of a temperature-sensitive human immunodeficiency virus type 1 reverse transcriptase mutant. The mutant virus, containing three charged residues within the RT finger domain changed to alanine (K64A, K66A, and D67A), replicated normally at 34.5 but not 39.5 degrees C. 1998 Journal of virology Abstract HIV D67A;K64A;K66A 116;100;106 120;104;110 RT 63 65 9499103 Human immunodeficiency virus replication and genotypic resistance in blood and lymph nodes after a year of potent antiretroviral therapy. A special effort was made to obtain sequences from patients with undetectable plasma RNA, emphasizing the rapidly emerging lamivudine-associated M184V mutation. 1998 Journal of virology Abstract HIV M184V 145 150 9512543 The processivity of DNA synthesis exhibited by drug-resistant variants of human immunodeficiency virus type-1 reverse transcriptase. In the present study we have conducted a comparative analysis of the processivity of DNA synthesis on both DNA and RNA templates of the Leu74Val, Glu89Gly, Tyr183Phe and Met184Leu drug-resistant mutants of HIV-1 RT in comparison with wild-type RT. 1998 Nucleic acids research Abstract HIV E89G;L74V;M184L;Y183F 146;136;170;156 154;144;179;165 RT;RT 212;244 214;246 9512543 The processivity of DNA synthesis exhibited by drug-resistant variants of human immunodeficiency virus type-1 reverse transcriptase. Leu74Val, Glu89Gly, Tyr183Phe, Met184Lue, Met184Val and Met184Ile) show enhanced accuracy of DNA synthesis relative to wild-type HIV-1 RT (as evident from a reduction in the capacity to introduce mispairs and to elongate them). 1998 Nucleic acids research Abstract HIV E89G;L74V;M184E;M184I;M184L;M184U;M184V;Y183F 10;0;31;56;31;31;42;20 18;8;40;65;40;40;51;29 RT 135 137 9514745 Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. The combination of M184V and E89G displayed synergistic resistance against ddCTP but not 3TCTP, while viruses containing only E89G were highly resistant to 3TCTP and displayed low-level resistance to ddCTP. 1998 Journal of molecular biology Abstract HIV E89G;E89G;M184V 29;126;19 33;130;24 9514745 Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. The K65R mutation, that confers low level resistance to both 3TC and ddC, can also restore sensitivity to AZT. 1998 Journal of molecular biology Abstract HIV K65R 4 8 9514745 Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. The M184V mutation, that confers high and low-level resistance to 3TC and ddC, respectively, can restore sensitivity to AZT when introduced into RT against a background of AZT-resistance. 1998 Journal of molecular biology Abstract HIV M184V 4 9 RT 145 147 9514745 Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. To explore this subject further, we have used an endogenous RT reaction to study mutated viruses containing M184V alone or M184V combined with each of the K65R, E89G or both the M41L and T215Y substitutions. 1998 Journal of molecular biology Abstract HIV E89G;K65R;M184V;M184V;M41L;T215Y 161;155;108;123;178;187 165;159;113;128;182;192 RT 60 62 9514745 Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. We now show that viruses containing both M184V and K65R displayed synergistic resistance to 3TC triphosphate (3TCTP), while the same combination yielded the same level of resistance to ddC triphosphate (ddCTP) as that manifested by K65R alone. 1998 Journal of molecular biology Abstract HIV K65R;K65R;M184V 51;232;41 55;236;46 9515572 Retention of marked sensitivity to (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-di hydroquin oxaline-2(1H)-thione (HBY 097) by an azidothymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) strain subcultured in the combined presence of quinoxaline HBY 097 and 2',3'-dideoxy-3'-thiacytidine (lamivudine). An azidothymidine (AZT)-resistant virus strain (HIV-1/AZT) (containing the 67 Asp --> Asn, 70 Lys --> Arg, 215 Thr --> Phe and 219 Lys --> Gln mutations into its reverse transcriptase) was grown in the combined presence of 2',3'-dideoxy-3'-thiacytidine (3TC, lamivudine) and the nonnucleoside reverse transcriptase inhibitor (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-dih ydroquinoxaine-2(1H)-thione (quinoxaline HBY 097). 1998 Biochemical pharmacology Abstract HIV K219Q;T215P 127;107 142;122 NNRTI;RT;Asp 279;162;78 314;183;81 9517942 1,1,3-Trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: a new class of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors with anti-HIV-1 activity. HIV-1 strains containing the L100I, K103N, V106A, E138K, Y181C, or Y188H mutations in their reverse transcriptase (RT) displayed reduced sensitivity to the compounds. 1998 Antimicrobial agents and chemotherapy Abstract HIV E138K;K103N;L100I;V106A;Y181C;Y188H 50;36;29;43;57;67 55;41;34;48;62;72 RT;RT 92;115 113;117 9517942 1,1,3-Trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: a new class of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors with anti-HIV-1 activity. HIV-1-resistant virus containing the V179D mutation in the RT was selected after approximately six passages of HIV-1 (IIIB) in CEM cells in the presence of different concentrations of QM96521. 1998 Antimicrobial agents and chemotherapy Abstract HIV V179D 37 42 RT 59 61 9520304 Construction and characterization of a radio-iodinatable mutant of recombinant human CD4. Moreover, trace-labeled [125I]-F179Y rsCD4(183) has the same affinity for HIV-1 rgp120 as unlabeled WT rsCD4. 1997 Journal of immunological methods Abstract HIV F179Y 31 36 9520304 Construction and characterization of a radio-iodinatable mutant of recombinant human CD4. The improved activity of trace-labeled [125I]-F179Y rsCD4(183) appears to be due to effective competition by Y179 for reactive iodine species that, in WT rsCD4, react with traces of denatured protein and/or with residues critical for activity or conformational integrity. 1997 Journal of immunological methods Abstract HIV F179Y 46 51 9520304 Construction and characterization of a radio-iodinatable mutant of recombinant human CD4. We have generated an iodinatable mutant of rsCD4 by substituting Tyr for Phe(179) in the flexible, solvent-exposed C-terminal region of rsCD4(183), a truncated form of CD4 that consists of the first 183 residues of CD4 and includes the binding sites for HIV-1 gp120 and MHC class II molecules. 1997 Journal of immunological methods Abstract HIV F179Y 65 81 gp120 260 265 9520304 Construction and characterization of a radio-iodinatable mutant of recombinant human CD4. When F179Y rsCD4(183) is iodinated under trace-labeling conditions, the efficiency of 125I incorporation and the percentage of iodinated molecules that are active are much enhanced compared with WT rsCD4. 1997 Journal of immunological methods Abstract HIV F179Y 5 10 9521105 Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant. In order to understand the significance of this difference between HIV-1 protease and homologous, eukaryotic aspartic proteases, we solved the three-dimensional structure of A28S mutant HIV-1 protease in complex with a peptidic inhibitor U-89360E. 1998 Protein science Abstract HIV A28S 174 178 PR;PR;PR 73;118;192 81;127;200 9521105 Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant. The mutation Ala28 to serine in human immunodeficiency virus, type 1, (HIV-1) protease introduces putative hydrogen bonds to each active-site carboxyl group. 1998 Protein science Abstract HIV A28S 13 28 PR 78 86 9521772 Structural basis for specificity of retroviral proteases. The variant has 9 substitutions (S38T, I42D, I44V, M73V, A100L, V104T, R105P, G106V, and S107N) of structurally equivalent residues from HIV-1 protease. 1998 Biochemistry Abstract HIV A100L;G106V;I42D;I44V;M73V;R105P;S107N;S38T;V104T 57;78;39;45;51;71;89;33;64 62;83;43;49;55;76;94;37;69 PR 143 151 9525609 The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity. The appearance, in the reverse transcriptase (RT), of the Q151M mutation in such variants precedes the sequential appearance of three or four additional mutations, resulting in a highly resistant virus. 1998 Journal of virology Abstract HIV Q151M 58 63 RT;RT 23;46 44;48 9525609 The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity. The nucleoside analog resistance mutations in the beta9-beta10 (M184V) and the beta5a (E89G) strands of HIV-1 RT were previously shown to increase the fidelity of deoxynucleoside triphosphate insertion. 1998 Journal of virology Abstract HIV E89G;M184V 87;64 91;69 RT 110 112 9525609 The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity. The overall error rates for the wild-type, the Q151M, and the VILYM RTs were 4.5 x 10(-5), 4.0 x 10(-5), and 2.3 x 10(-5) per nucleotide, respectively. 1998 Journal of virology Abstract HIV Q151M 47 52 RT 68 71 9525609 The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity. The Q151M RT mutant generated new hot spots, which were not observed for wild-type HIV-1 RT previously. 1998 Journal of virology Abstract HIV Q151M 4 9 RT;RT 10;89 12;91 9525609 The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity. Therefore, we have examined wild-type HIV-1BH10 RT and two nucleoside analog-resistant variants, the Q151M and A62V/V75I/F77L/F116Y/Q151M (VILYM) RTs, for their overall forward mutation rates in an M13 gapped-duplex assay that utilizes lacZ alpha as a reporter. 1998 Journal of virology Abstract HIV A62V;F116Y;F77L;Q151M;V75I;Q151M 111;126;121;132;116;101 115;131;125;137;120;106 RT;RT 48;146 50;149 9527805 A mutation at position 190 of human immunodeficiency virus type 1 reverse transcriptase interacts with mutations at positions 74 and 75 via the template primer. The combination of either of the mutations L74V or V75I with the G190E mutation appears to be compensatory and mitigates many of the deleterious effects of the G190E mutation. 1998 Antimicrobial agents and chemotherapy Abstract HIV G190E;G190E;L74V;V75I 65;160;43;51 70;165;47;55 9527805 A mutation at position 190 of human immunodeficiency virus type 1 reverse transcriptase interacts with mutations at positions 74 and 75 via the template primer. The mutation G190E, which is responsible for resistance to certain nonnucleoside inhibitors, results in RT that has significantly less polymerase activity and that is less processive than wild-type RT. 1998 Antimicrobial agents and chemotherapy Abstract HIV G190E 13 18 Pol;RT;RT 135;104;198 145;106;200 9527815 Estimate of the frequency of human immunodeficiency virus type 1 protease inhibitor resistance within unselected virus populations in vitro. Two variants with single mutations responsible for drug resistance (V82A and N88S) were quantifiably isolated after only one round of replication, yielding a crude frequency estimate of at least 1 SC-55389A-resistant variant per 3.5 x 10(5) wild-type infectious units. 1998 Antimicrobial agents and chemotherapy Abstract HIV N88S;V82A 77;68 81;73 9557630 Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants. Overgrowth of these variants suggests that they have better fitness than the original T215Y variant. 1998 Journal of virology Abstract HIV T215Y 86 91 9557630 Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants. Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in successive plasma samples from eight seroconverting patients infected with virus bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV) resistance. 1998 Journal of virology Abstract HIV T215F;T215Y 241;241 248;248 RT;RT 61;84 82;86 9557630 Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants. Three patients had the M41L amino acid change, which persisted. 1998 Journal of virology Abstract HIV M41L 23 27 9557630 Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants. Two patients had both the D67N and the K70R amino acid substitutions; reversion to the wild type was seen at both positions in one of these patients and at codon 70 in the other one. 1998 Journal of virology Abstract HIV D67N;K70R 26;39 30;43 9557659 Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro. The order of relative fitness was wild type > K70R >> T215Y = M41L+T215Y > M41L. 1998 Journal of virology Abstract HIV K70R;M41L;M41L;T215Y;T215Y 46;62;75;54;67 50;66;79;59;72 9557659 Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro. These variants were engineered to contain commonly observed zidovudine resistance mutations in the HIV-1 reverse transcriptase (M41L, K70R, T215Y, and M41L+T215Y). 1998 Journal of virology Abstract HIV K70R;M41L;M41L;T215Y;T215Y 134;128;151;140;156 138;132;155;145;161 RT 105 126 9557676 The role of nucleocapsid and U5 stem/A-rich loop sequences in tRNA(3Lys) genomic placement and initiation of reverse transcription in human immunodeficiency virus type 1. For other linker mutations [R7R10K11 S, R32G, and S3(32-34)], packaging of Pr160(gag-pol) and tRNA(3Lys) was not affected, but genomic placement was, and placement could not be rescued by cotransfection with plasmids coding for either Pr55gag or Pr160(gag-pol). 1998 Journal of virology Abstract HIV R32G 40 44 GagPol;GagPol;PR;PR;PR 81;252;75;235;246 88;259;77;237;248 9557676 The role of nucleocapsid and U5 stem/A-rich loop sequences in tRNA(3Lys) genomic placement and initiation of reverse transcription in human immunodeficiency virus type 1. One mutation in the linker region between the two Cys-His boxes, P31L, prevented packaging of both Pr160(gag-pol) and tRNA(3Lys) and prevented the genomic placement of tRNA(3Lys). 1998 Journal of virology Abstract HIV P31L 65 69 GagPol;PR 105;99 112;101 9557691 T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1alpha contains mutations in the envelope gp120 but does not show a switch in coreceptor use. The SDF-1alpha(res) virus contained the following mutations in the gp120 molecule: N106K in the V1 loop; S134N and F145L in the V2 loop; F245I in the C2 loop; K269E, Q278H, I288V, and N293D in the V3 loop; a deletion of 5 amino acids (FNSTW) at positions 364 to 368 in the V4 loop; and R378T in the CD4 binding domain. 1998 Journal of virology Abstract HIV F145L;F245I;I288V;K269E;N106K;N293D;Q278H;R378T;S134N 115;137;173;159;83;184;166;286;105 120;142;178;164;88;189;171;291;110 gp120 67 72 9557700 The putative alpha helix 2 of human immunodeficiency virus type 1 Vpr contains a determinant which is responsible for the nuclear translocation of proviral DNA in growth-arrested cells. In particular, the Vpr Q65E mutant, which contains a substitution in the second predicted amphipathic alpha-helical structure located in the central region of the protein, is associated with an impairment of the protein nuclear localization and a concomitant reduction of the nuclear transport of proviral DNA. 1998 Journal of virology Abstract HIV Q65E 23 27 Vpr 19 22 9557711 Increased misincorporation fidelity observed for nucleoside analog resistance mutations M184V and E89G in human immunodeficiency virus type 1 reverse transcriptase does not correlate with the overall error rate measured in vitro. Therefore, the overall polymerase fidelities of wild-type, E89G, M184V, and E89G/M184V HIV-1 RTs are similar (less than twofold differences) for DNA-dependent DNA synthesis. 1998 Journal of virology Abstract HIV E89G;E89G;M184V;M184V 59;76;81;65 63;80;86;70 Pol;RT 23;93 33;96 9557711 Increased misincorporation fidelity observed for nucleoside analog resistance mutations M184V and E89G in human immunodeficiency virus type 1 reverse transcriptase does not correlate with the overall error rate measured in vitro. To evaluate the contribution of increased nucleotide insertion and primer extension fidelities on the overall error rate of HIV-1 RT, we have measured the impact of two such mutations, E89G and M184V, on DNA copying fidelity in an M13 phage-based forward mutation assay. 1998 Journal of virology Abstract HIV E89G;M184V 185;194 189;199 RT 130 132 9557711 Increased misincorporation fidelity observed for nucleoside analog resistance mutations M184V and E89G in human immunodeficiency virus type 1 reverse transcriptase does not correlate with the overall error rate measured in vitro. Using this assay, we observed mutation frequencies of 8.60 x 10(-3), 6.26 x 10(-3), 5.53 x 10(-3), and 12.30 x 10(-3) for wild-type, E89G, M184V, and double-mutant E89G/M184V HIV-1 RTs, respectively. 1998 Journal of virology Abstract HIV E89G;E89G;M184V;M184V 133;164;169;139 137;168;174;144 RT 181 184 9557731 Cryoelectron microscopic examination of human immunodeficiency virus type 1 virions with mutations in the cyclophilin A binding loop. Although viral RNA incorporation and protease cleavage of the Gag precursor were not affected by these mutations, cryoelectron microscopy revealed a loss of virion maturation in P231A particles. 1998 Journal of virology Abstract HIV P231A 178 183 PR;Gag 37;62 45;65 9557739 PITALRE, the catalytic subunit of TAK, is required for human immunodeficiency virus Tat transactivation in vivo. A catalytic mutant of PITALRE, D167N, was found to be more efficient than wild-type PITALRE in squelching Tat transactivation. 1998 Journal of virology Abstract HIV D167N 31 36 Tat 106 109 9557739 PITALRE, the catalytic subunit of TAK, is required for human immunodeficiency virus Tat transactivation in vivo. Neither wild-type PITALRE nor D167N was able to squelch transactivation of the human T-cell leukemia type 1 LTR by the Tax protein. 1998 Journal of virology Abstract HIV D167N 30 35 LTR 108 111 9558316 Fidelity of mutant HIV-1 reverse transcriptases: interaction with the single-stranded template influences the accuracy of DNA synthesis. More detailed analysis of DNA-dependent polymerization showed that the D76V mutation conferred an up to 14-fold increase in fidelity of nucleotide insertion and a 9-fold reduced mutation rate in an M13mp2 lacZalpha forward mutation assay. 1998 Biochemistry Abstract HIV D76V 71 75 9558316 Fidelity of mutant HIV-1 reverse transcriptases: interaction with the single-stranded template influences the accuracy of DNA synthesis. Substitution at D76 with positively charged (D76R) and nonpolar (D76V and D76I) residues increased replicational accuracy, while substitutions with negatively charged (D76E) and polar residues (D76S and D76C) had little effect on fidelity. 1998 Biochemistry Abstract HIV D76C;D76E;D76I;D76R;D76S;D76V 203;168;74;45;194;65 207;172;78;49;199;70 9558316 Fidelity of mutant HIV-1 reverse transcriptases: interaction with the single-stranded template influences the accuracy of DNA synthesis. We show here that one of these mutants, D76V, exhibits increased accuracy of copying both DNA and RNA templates in a primer extension assay with biased dNTP pools. 1998 Biochemistry Abstract HIV D76V 40 44 9561202 In vitro selection and characterization of VX-478 resistant HIV-1 variants. By direct PCR analysis of selected viruses, a number of mutations were identified (L10F, M46I, I47V, I50V and I84V) in the protease gene. 1998 Advances in experimental medicine and biology Abstract HIV I47V;I50V;I84V;L10F;M46I 95;101;110;83;89 99;105;114;87;93 PR 123 131 9561202 In vitro selection and characterization of VX-478 resistant HIV-1 variants. For VX-478, significant increases in IC90 and Ki were observed for virus or protease, respectively, containing I50V single mutation or an M46I/I47V/I50V triple mutation. 1998 Advances in experimental medicine and biology Abstract HIV I47V;I50V;M46I;I50V 143;148;138;111 147;152;142;115 PR 76 84 9573250 Structure-based mutational analysis of the C-terminal DNA-binding domain of human immunodeficiency virus type 1 integrase: critical residues for protein oligomerization and DNA binding. Amino acid substitution of residues located in the hydrophobic dimer interface, such as L241A and L242A, results in the loss of oligomerization of IN; consequently, the levels of 3' processing, DNA strand transfer, and intramolecular disintegration are strongly reduced. 1998 Journal of virology Abstract HIV L241A;L242A 88;98 93;103 IN 147 149 9573252 3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants. In addition, the presence of AZT also causes viruses containing the M41L and T215Y substitutions to have diminished sensitivity to other nucleoside analogs (i.e., ddC, ddI, and d4T). 1998 Journal of virology Abstract HIV M41L;T215Y 68;77 72;82 9573252 3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants. Our results suggest that the use of AZT may be contraindicated in those patients for whom resistance to this compound (M41L and/or T215Y) has been demonstrated. 1998 Journal of virology Abstract HIV M41L;T215Y 119;131 124;136 9573252 3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants. This AZT-mediated cross-resistance may help to explain the virological failure of treatment regimens that included ddI plus AZT or ddC plus AZT in situations in which the T215Y and/or M41L mutations were present (F. 1998 Journal of virology Abstract HIV M41L;T215Y 184;171 188;176 9573252 3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants. Through use of PCR amplifications, we discovered an AZT-mediated stimulation of reverse transcription by AZT-resistant viruses carrying the M41L and T215Y mutations that can apparently override the inhibitory effects of AZT-5'-triphosphate. 1998 Journal of virology Abstract HIV M41L;T215Y 140;149 144;154 RT 80 101 9573274 Effects of mutations in residues near the active site of human immunodeficiency virus type 1 integrase on specific enzyme-substrate interactions. The phenotype of IN(Q148L) suggested that Q148 may be involved in interactions with the 5' dinucleotide of the viral DNA end. 1998 Journal of virology Abstract HIV Q148L 20 25 IN 17 19 9573280 A novel polymorphism at codon 333 of human immunodeficiency virus type 1 reverse transcriptase can facilitate dual resistance to zidovudine and L-2',3'-dideoxy-3'-thiacytidine. Genetic mapping and site-directed mutagenesis experiments demonstrated that a polymorphism at codon 333 (Gly to Glu) of human immunodeficiency virus type 1 reverse transcriptase (RT) was critical in facilitating dual resistance in a complex background of AZT and 3TC resistance mutations. 1998 Journal of virology Abstract HIV G333E 100 116 RT;RT 156;179 177;181 9573287 Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. A virologic response beyond 60 days was not observed unless plasma HIV RNA levels were suppressed below 2,000 copies/ml, consistent with estimates from V82A doubling times for selection of a single resistance mutation to dominate the replicating population. 1998 Journal of virology Abstract HIV V82A 152 156 9573287 Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. An L63P/A mutation was commonly present at baseline even in subjects with a durable virologic response. 1998 Journal of virology Abstract HIV L63A;L63P 3;3 9;9 9573287 Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. Doubling times of the V82A mutant virus were estimated to be 2.4 to 4.8 days. 1998 Journal of virology Abstract HIV V82A 22 26 9573287 Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. Ongoing viral replication in the presence of drugs resulted in the appearance of additional genotypic changes, including the L90M saquinavir resistance mutation, and decreased phenotypic susceptibility. 1998 Journal of virology Abstract HIV L90M 125 129 9573287 Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. The concomitant acquisition of an L63P/A mutation with the V82A/F mutation at the time when plasma RNA levels rebounded suggests a role for the L63P/A mutation in improving the fitness of the V82A/F mutation. 1998 Journal of virology Abstract HIV L63A;L63A;L63P;L63P;V82A;V82A;V82F;V82F 34;144;34;144;59;192;59;192 40;150;40;150;65;198;65;198 9573287 Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. The relative fitness of the protease V82A ritonavir resistance mutation and reverse transcriptase T215Y/F zidovudine resistance mutation following drug withdrawal were estimated to be 96 to 98% that of the wild type. 1998 Journal of virology Abstract HIV T215F;T215Y;V82A 98;98;37 105;105;41 RT;PR 76;28 97;36 9573309 Human immunodeficiency virus type 1 protease genotypes and in vitro protease inhibitor susceptibilities of isolates from individuals who were switched to other protease inhibitors after long-term saquinavir treatment. In addition, all six patients who developed the G48V mutation during saquinavir therapy developed the V82A mutation either on continued saquinavir or after a switch to nelfinavir or indinavir. 1998 Journal of virology Abstract HIV G48V;V82A 48;102 52;106 9573309 Human immunodeficiency virus type 1 protease genotypes and in vitro protease inhibitor susceptibilities of isolates from individuals who were switched to other protease inhibitors after long-term saquinavir treatment. In vitro susceptibility assays showed that all 13 isolates with reduced susceptibilities to two or more protease inhibitors had either the G48V or L90M mutation, along with an average of six other protease mutations. 1998 Journal of virology Abstract HIV G48V;L90M 139;147 143;151 PR;PR 104;197 112;205 9573309 Human immunodeficiency virus type 1 protease genotypes and in vitro protease inhibitor susceptibilities of isolates from individuals who were switched to other protease inhibitors after long-term saquinavir treatment. Protease gene sequencing results from patients treated with saquinavir showed significant increases in the frequency of the G48V protease mutation in patients receiving higher doses of the drug. 1998 Journal of virology Abstract HIV G48V 124 128 PR;PR 0;129 8;137 9573309 Human immunodeficiency virus type 1 protease genotypes and in vitro protease inhibitor susceptibilities of isolates from individuals who were switched to other protease inhibitors after long-term saquinavir treatment. Reduced susceptibility to nelfinavir was found in 14 isolates, but only 1 possessed the D30N mutation. 1998 Journal of virology Abstract HIV D30N 88 92 9578482 Helical and coiled-coil-forming properties of peptides derived from and inhibiting human immunodeficiency virus type 1 integrase assessed by 1H-NMR--use of NH temperature coefficients to probe coiled-coil structures. IN-(147-175)-peptide contains four heptad repeats and displays a high propensity for coiled-coil formation while its [P159]IN-(147-175)-peptide analog (Lys159-->Pro in the protein, Lys13-->Pro in the peptide) is unable to form a stable coiled-coil and is devoid of inhibitory activity [Sourgen, F., Maroun, R. 1998 European journal of biochemistry Abstract HIV K13P;K159P 181;152 192;165 IN;IN 0;123 2;125 9593005 Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance. Investigations were done to determine whether the replication kinetics of human immunodeficiency virus (HIV)-1 were altered when the virus acquired a set or subsets of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene conferring resistance to multiple dideoxynucleosides. 1998 The Journal of infectious diseases Abstract HIV A62V;F116Y;F77L;Q151M;V75I 184;202;196;213;190 188;207;200;218;194 Pol 227 230 9603966 Mutating a region of HIV-1 reverse transcriptase implicated in tRNA(Lys-3) binding and the consequences for (-)-strand DNA synthesis. p66 subunits containing K249Q, K311Q, K311E, and a dual R307E/K311E mutation formed a stable dimer with wild type p51. 1998 The Journal of biological chemistry Abstract HIV K249Q;K311E;K311E;K311Q;R307E 24;62;38;31;56 29;67;43;36;61 9603966 Mutating a region of HIV-1 reverse transcriptase implicated in tRNA(Lys-3) binding and the consequences for (-)-strand DNA synthesis. Unlike wild type RT, mutants p66(K311Q)/p51 and p66(K311E)/p51 failed to protect the tRNA anticodon domain from chemical cleavage, indicating a significant structural alteration in the binary RT.tRNA complex. 1998 The Journal of biological chemistry Abstract HIV K311E;K311Q 52;33 57;38 RT;RT 17;192 19;194 9603976 Enhanced binding of azidothymidine-resistant human immunodeficiency virus 1 reverse transcriptase to the 3'-azido-3'-deoxythymidine 5'-monophosphate-terminated primer. Human immunodeficiency virus type 1 is resistant to 3'-azido-3'-deoxythymidine (AZT) when four amino acid substitutions (D67N, K70R, T215F, and K219Q) are present simultaneously in its reverse transcriptase. 1998 The Journal of biological chemistry Abstract HIV D67N;K219Q;K70R;T215F 121;144;127;133 125;149;131;138 RT 185 206 9607827 Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy. A set of five reverse transcriptase mutations, which include Q151M, is known to confer multi-dideoxynucleoside resistance (MDR) in human immunodeficiency virus type 1 (HIV-1). 1998 The Journal of infectious diseases Abstract HIV Q151M 61 66 RT 14 35 9607827 Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy. Q151M was among the first of the substitutions to appear. 1998 The Journal of infectious diseases Abstract HIV Q151M 0 5 9607830 A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection. Studies of viral genotype and phenotype after virus rebound revealed that the initial active site mutation allowing for nelfinavir resistance is mediated by a unique amino acid substitution in the HIV-1 protease D30N, which does not confer in vitro phenotypic cross-resistance to the currently available protease inhibitors. 1998 The Journal of infectious diseases Abstract HIV D30N 212 216 PR;PR 203;304 211;312 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. First, variants of HIV with the M184I substitution appear transiently, followed by viruses containing the M184V substitution, which persist and become the dominant variant for the duration of therapy. 1998 Nucleic acids research Abstract HIV M184I;M184V 32;106 37;111 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Interestingly, the M184I variant RT displays significantly altered error specificity, both in terms of error rate at specific sites and in the overall ratio of substitution to frameshift mutations in the entire target. 1998 Nucleic acids research Abstract HIV M184I 19 24 RT 33 35 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Of the nucleoside analog resistance mutations studied using the forward assay, the M184I variant has shown the greatest increase in fidelity observed to date. 1998 Nucleic acids research Abstract HIV M184I 83 88 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Recent studies have shown that 3TC resistance mutations, including M184I, increase the nucleotide insertion and mispair extension fidelity. 1998 Nucleic acids research Abstract HIV M184I 67 72 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Therefore, we have examined the effects of the M184I mutation on the overall polymerase fidelity of HIV-1 RT via an M13-based forward mutation assay. 1998 Nucleic acids research Abstract HIV M184I 47 52 Pol;RT 77;106 87;108 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. This represents a 4-fold increase in fidelity over wild-type HIV-1Hxb2RT (7.0 x 10(-5) per nucleotide) and a 2.5-fold increase in fidelity over the M184V variant (4.3 x 10(-5) per nucleotide). 1998 Nucleic acids research Abstract HIV M184V 148 153 9611256 The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. We found the overall error rate of the M184I variant of HIV-1 RT to be 1.7 x 10(-5) per nucleotide. 1998 Nucleic acids research Abstract HIV M184I 39 44 RT 62 64 9619801 The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors. M184V per se is not expected to compromise subsequent treatment with NRTI such as didanosine-stavudine or combinations containing abacavir. 1998 AIDS (London, England) Abstract HIV M184V 0 5 NRTI 69 73 9619801 The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors. OBJECTIVE: To investigate the prevalence and magnitude of M184V-mediated changes in susceptibility to zalcitabine, didanosine, stavudine and abacavir (1592U89 succinate) in a cohort of lamivudine-treated patients. 1998 AIDS (London, England) Abstract HIV M184V 58 63 9619801 The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors. There were no other genotypic changes in addition to M184V known to be associated with abacavir resistance. 1998 AIDS (London, England) Abstract HIV M184V 53 58 9621042 Role of the SH3-ligand domain of simian immunodeficiency virus Nef in interaction with Nef-associated kinase and simian AIDS in rhesus macaques. To test the significance of the PxxP motif of Nef for viral pathogenesis, each proline was mutated to an alanine to produce the viral clone SIVmac239-P104A/P107A. 1998 Journal of virology Abstract HIV P104A;P107A 150;156 155;161 Nef 46 49 9622549 New alkenyldiarylmethanes with enhanced potencies as anti-HIV agents which act as non-nucleoside reverse transcriptase inhibitors. Thus, ADAM II could serve as an adjunct therapy to AZT and NNRTIs that select for L100I resistance mutations. 1998 Journal of medicinal chemistry Abstract HIV L100I 82 87 NNRTI 59 65 9624472 S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. 1998 Antimicrobial agents and chemotherapy Abstract HIV Y181C 164 169 NNRTI 132 137 9624472 S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. 1998 Antimicrobial agents and chemotherapy Abstract HIV F227L;L234I 168;177 173;182 9624498 Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human immunodeficiency virus strains. Among a large panel of drug-resistant HIV type 1 variants, only the K65R virus was resistant to PMPA. 1998 Antimicrobial agents and chemotherapy Abstract HIV K65R 68 72 9624498 Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human immunodeficiency virus strains. Among a panel of seven primary clinical isolates from patients with diverse treatment histories, only one isolate showed reduced susceptibility to PMPA and was found to carry three mutations (M41L, T69N, R73K) in its reverse transcriptase catalytic domain. 1998 Antimicrobial agents and chemotherapy Abstract HIV M41L;R73K;T69N 192;204;198 196;208;202 RT 217 238 9624498 Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human immunodeficiency virus strains. K65R virus also showed reduced susceptibility to bis(poc)PMPA, although the prodrug could still inhibit these viruses at submicromolar, nontoxic concentrations. 1998 Antimicrobial agents and chemotherapy Abstract HIV K65R 0 4 9628735 Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and antiviral potency. Four of the five mutations studied (V82F, V82A, I84V, and V82F/I84V) had been identified as conferring resistance during in vitro selection using a protease inhibitor. 1998 Biochemistry Abstract HIV I84V;I84V;V82A;V82F;V82F 63;48;42;36;58 67;52;46;40;62 PR 148 156 9628735 Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and antiviral potency. Much larger changes compared to wild type were observed for the double mutation V82F/I84V both for Ki (10-2000-fold) and for IC90 (0.7-377-fold). 1998 Biochemistry Abstract HIV I84V;V82F 85;80 89;84 9628735 Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and antiviral potency. The single mutations V82F and I84V caused changes with various inhibitors ranging from 0.3- to 86-fold in Ki and from 0.1- to 11-fold in IC90. 1998 Biochemistry Abstract HIV I84V;V82F 30;21 34;25 9632373 Nonsymmetric P2/P2' cyclic urea HIV protease inhibitors. Structure-activity relationship, bioavailability, and resistance profile of monoindazole-substituted P2 analogues. However, the resistance profiles of these compounds were inadequate, especially against the double (I84V/V82F) and ritonavir-selected mutant viruses. 1998 Journal of medicinal chemistry Abstract HIV I84V;V82F 100;105 104;109 9634074 A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152. An explanation for the markedly increased sensitivity of the P225H mutant HIV-1 RT to BHAP and not to the other NNRTIs was provided by the unique features of the X-ray structure of the RT-BHAP complex. 1998 The Journal of general virology Abstract HIV P225H 61 66 NNRTI;RT;RT 112;80;185 118;82;187 9634074 A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152. Construction of both recombinant viruses and recombinant RTs containing the V106A, P225H and V106A+P225H mutations revealed that P225H was indeed responsible for the marked potentiation of the antiviral activity of BHAP against the P225H single-mutant virus and the V106A+P225H double-mutant virus when compared to wild-type and V106A single-mutant viruses, respectively. 1998 The Journal of general virology Abstract HIV P225H;P225H;P225H;P225H;P225H;V106A;V106A;V106A;V106A 83;99;129;232;272;76;93;266;329 88;104;134;237;277;81;98;271;334 RT 57 60 9634074 A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152. Surprisingly, the addition of the P225H mutation to the V106A RT mutant genetic background resensitized the V106A RT mutant virus to the non-nucleoside RT inhibitor (NNRTI) BHAP U-90152, but not to other NNRTIs. 1998 The Journal of general virology Abstract HIV P225H;V106A;V106A 34;56;108 39;61;113 NNRTI;NNRTI;RT;RT;RT 166;204;62;114;152 171;210;64;116;154 9634074 A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152. Two mutant virus strains in which the novel P225H mutation appeared in a V106A reverse transcriptase (RT)-mutated genetic background upon treatment of human immunodeficiency virus type 1 (HIV-1) with quinoxaline S-2720 were isolated. 1998 The Journal of general virology Abstract HIV P225H;V106A 44;73 49;78 RT;RT 79;102 100;104 9643373 Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. In contrast, M184V-containing HIV first showed escape between days 25 and 32 and sequence analysis revealed an aspartate-to-tyrosine change at amino acid 5 in V3 (N5Y; AAC --> TAC) in two of six clones at day 36 and in five of five clones at day 55. 1998 AIDS research and human retroviruses Abstract HIV D5Y;M184V;N5Y 111;13;163 155;18;166 9643373 Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. In contrast, the N5Y substitution seen with M184V-containing HIV-1 is an A --> T transversion in V3. 1998 AIDS research and human retroviruses Abstract HIV M184V;N5Y 44;17 49;20 9643373 Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. Sequence analysis revealed an arginine-to-lysine change within the GPGR epitope in the V3 loop (R20K, AGA --> AAA) in six of six clones sequenced after day 36. 1998 AIDS research and human retroviruses Abstract HIV R20K 96 100 9643373 Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. The escape mutation in the wild type is consistent with the G --> A hypermutation observed in wild-type HIV-1, recently shown to cause an initial M184I change (before M184V) in 3TC-treated patients. 1998 AIDS research and human retroviruses Abstract HIV M184I;M184V 146;167 151;172 9643373 Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) encodes high-level resistance to the (-)-enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) and low-level resistance to each of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). 1998 AIDS research and human retroviruses Abstract HIV M184V 4 9 RT;RT 70;93 91;95 9643373 Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. To assess the effect of this substitution on genetic variation in the HIV env region, we cultured both M184V-containing and wild-type BH10 in MT-4 cells in the presence of the neutralizing monoclonal antibody 447-52D, targeted to the GPGR epitope within the V3 loop of gp120. 1998 AIDS research and human retroviruses Abstract HIV M184V 103 108 gp120;Env 269;74 274;77 9657675 Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of human immunodeficiency virus type-1 reverse transcriptase is compensated by Met to Val substitution within the same motif. Curiously, the double mutant did not exhibit any synergistic effect in regard to fidelity of DNA synthesis as might be expected since both the single mutations (Y183F, M184V) exhibited enhanced fidelity compared to the wild-type enzyme. 1998 Biochemistry Abstract HIV M184V;Y183F 168;161 173;166 9657675 Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of human immunodeficiency virus type-1 reverse transcriptase is compensated by Met to Val substitution within the same motif. However, the fidelity of DNA synthesis by the Y183F and Y183A mutants was increased significantly compared to the wild-type enzyme. 1998 Biochemistry Abstract HIV Y183A;Y183F 56;46 61;51 9657675 Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of human immunodeficiency virus type-1 reverse transcriptase is compensated by Met to Val substitution within the same motif. In an attempt to understand the function of Tyr183 in the catalytic mechanism, we generated mutants of this residue (Y183F and Y183A) and subjected them to in-depth analysis. 1998 Biochemistry Abstract HIV Y183A;Y183F 127;117 132;123 9657675 Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of human immunodeficiency virus type-1 reverse transcriptase is compensated by Met to Val substitution within the same motif. The loss of dNTP binding as well as decreased processivity of DNA synthesis exhibited by the Y183F mutant was also compensated by mutation at the second site. 1998 Biochemistry Abstract HIV Y183F 93 98 9658084 Human immunodeficiency virus type 1 replication is modulated by host cyclophilin A expression levels. In contrast, A224E mutant virus is dead in H9 T cells, although replication is rescued by cyclosporine or by expression in cis of a Gag mutant that decreases cyclophilin A-affinity. 1998 Journal of virology Abstract HIV A224E 13 18 Gag 132 135 9658084 Human immunodeficiency virus type 1 replication is modulated by host cyclophilin A expression levels. The A224E Gag mutant has no effect on cyclophilin A affinity but renders HIV-1 replication cyclosporine resistant in Jurkat T cells. 1998 Journal of virology Abstract HIV A224E 4 9 Gag 10 13 9658084 Human immunodeficiency virus type 1 replication is modulated by host cyclophilin A expression levels. The observation that disruption of the Gag-cyclophilin A interaction rescues A224E mutant replication in H9 cells prompted experiments which revealed that, relative to Jurkat cells, H9 cells express greater quantities of cyclophilin A. 1998 Journal of virology Abstract HIV A224E 77 82 Gag 39 42 9658084 Human immunodeficiency virus type 1 replication is modulated by host cyclophilin A expression levels. The resulting larger quantity of cyclophilin A shown to be packaged into virions produced by H9 cells is presumably disruptive to the A224E mutant virion core. 1998 Journal of virology Abstract HIV A224E 134 139 9658134 Kinetics of antiviral activity by human immunodeficiency virus type 1-specific cytotoxic T lymphocytes (CTL) and rapid selection of CTL escape virus in vitro. TCC108-mediated inhibition of virus replication in peripheral blood mononuclear cells caused rapid selection of a virus with a mutation (69E-->K) in the Rev(67-75) CTL epitope which abolished recognition by TCC108 cells. 1998 Journal of virology Abstract HIV E69K 137 144 Rev 153 156 9660994 Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from AIDS patients after prolonged adefovir dipivoxil therapy. In vitro experiments demonstrated that either a K65R or a K70E mutation in HIV reverse transcriptase (RT) was selected in the presence of adefovir, conferring a 16- or 9-fold decrease in susceptibility to adefovir, respectively. 1998 Antimicrobial agents and chemotherapy Abstract HIV K65R;K70E 48;58 52;62 RT;RT 79;102 100;104 9660994 Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from AIDS patients after prolonged adefovir dipivoxil therapy. Viruses from two of the eight patients developed the K70E mutation while the patients were on therapy, but none of the viruses from patients developed the K65R RT substitution. 1998 Antimicrobial agents and chemotherapy Abstract HIV K65R;K70E 155;53 159;57 RT 160 162 9664204 Nelfinavir. A review of its therapeutic efficacy in HIV infection. A unique mutation at codon 30 (D30N) of the protease gene confers resistance to nelfinavir, but HIV with D30N mutation remains fully susceptible to indinavir, ritonavir and saquinavir in vitro. 1998 Drugs Abstract HIV D30N;D30N 31;105 35;109 PR 44 52 9678492 Analysis of HIV-1 Tat effects in Xenopus laevis embryos. Both Tat and Tat-C37S were found to be localized mainly in the nucleus. 1998 Journal of biomedical science Abstract HIV C37S 17 21 Tat;Tat 5;13 8;16 9678492 Analysis of HIV-1 Tat effects in Xenopus laevis embryos. The specificity of Tat effects was demonstrated by injecting a 'loss of function' mutant (Tat-C37S), lacking a single cysteine residue, which did not yield any effect. 1998 Journal of biomedical science Abstract HIV C37S 94 98 Tat;Tat 19;90 22;93 9685235 Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 7. 8-Arylethyldipyridodiazepinones as potent broad-spectrum inhibitors of wild-type and mutant enzymes. In particular, the mutation of residue 181 from tyrosine to cysteine (Y181C) is associated with resistance to most reported nonnucleoside inhibitors. 1998 Journal of medicinal chemistry Abstract HIV Y181C;Y181C 70;39 75;68 9685235 Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 7. 8-Arylethyldipyridodiazepinones as potent broad-spectrum inhibitors of wild-type and mutant enzymes. Introduction of an arylethyl substituent at the 8-position of the tricyclic dipyridodiazepinone skeleton confers enhanced potency against Y181C RT. 1998 Journal of medicinal chemistry Abstract HIV Y181C 138 143 RT 144 146 9685236 Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 8. 8-Aryloxymethyl- and 8-arylthiomethyldipyridodiazepinones. The most potent compounds were further evaluated against a panel of clinically significant mutant RT enzymes (K103N, V106A, G190A, P236L) and in cytotoxicity and in vitro metabolism assays. 1998 Journal of medicinal chemistry Abstract HIV G190A;K103N;P236L;V106A 124;110;131;117 129;115;136;122 RT 98 100 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. Genotypic analyses of samples from patients enrolled in a phase I/II clinical trial of adefovir dipivoxil demonstrated that the K70E RT mutation developed in two of 29 patients during extended therapy. 1998 Molecular pharmacology Abstract HIV K70E 128 132 RT 133 135 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. In single-cycle processivity studies, the M184V mutant was, as expected, notably impaired. 1998 Molecular pharmacology Abstract HIV M184V 42 47 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. Previous in vitro experiments have shown that HIV-1 recombinant viruses expressing either a K65R or a K70E mutation in reverse transcriptase (RT) have reduced sensitivity to PMEA and that the K70E mutant also has impaired replication capacity in vitro. 1998 Molecular pharmacology Abstract HIV K65R;K70E;K70E 92;102;192 96;106;196 RT;RT 119;142 140;144 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. The K70E mutant was also slightly impaired, whereas the K65R mutant was slightly more processive than wild-type. 1998 Molecular pharmacology Abstract HIV K65R;K70E 56;4 60;8 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. The Ki values for the K65R mutant were increased from wild-type by 2-5-fold against a variety of inhibitors, whereas the Ki values for the M184V mutant were increased 12-fold specifically for 2', 3'-dideoxy-3'-thiacytidine (3TC) triphosphate. 1998 Molecular pharmacology Abstract HIV K65R;M184V 22;139 26;144 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. The Ki values for the K70E mutant were increased for PMEA diphosphate and 3TC triphosphate by 2-3-fold. 1998 Molecular pharmacology Abstract HIV K70E 22 26 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. These results with recombinant K70E RT are consistent with the reduced in vitro replication capacity of the K70E RT mutant of HIV-1 and further demonstrate that the K70E mutation confers minor PMEA and 3TC resistance to HIV-1. 1998 Molecular pharmacology Abstract HIV K70E;K70E;K70E 31;108;165 35;112;169 RT;RT 36;113 38;115 9687570 Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. To further investigate the molecular mechanisms involved in the resistance to PMEA, we cloned, expressed, and purified HIV-1 RT enzymes carrying either the K65R or K70E and, for comparison, the M184V mutation. 1998 Molecular pharmacology Abstract HIV K65R;K70E;M184V 156;164;194 160;168;199 RT 125 127 9696850 In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. Further selection at a 3.0 microM inhibitor concentration resulted in an additional change at residue 47 (V47A), as well as reversion at residue 32 back to the wild-type sequence. 1998 Journal of virology Abstract HIV V47A 106 110 9696850 In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. Selection of viral variants with increasing concentrations of ABT-378 revealed a sequential appearance of mutations in the protease gene: I84V-L10F-M46I-T91S-V32I-I47V. 1998 Journal of virology Abstract HIV I47V;I84V;L10F;M46I;T91S;V32I 163;138;143;148;153;158 167;142;147;152;157;162 PR 123 131 9696850 In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. The p7/p1 mutation appeared very late during the selection process and was strongly associated with the emergence of the additional change at residue 47 (V47A) and the reversion at residue 32 back to the wild-type sequence. 1998 Journal of virology Abstract HIV V47A 154 158 9696874 Mutations in the primer grip of human immunodeficiency virus type 1 reverse transcriptase impair proviral DNA synthesis and virion maturation. Among a series of RT mutant viruses, three (M230A, L234D, and W239A) were found to be noninfectious or very poorly infectious. 1998 Journal of virology Abstract HIV L234D;M230A;W239A 51;44;62 56;49;67 RT 18 20 9696874 Mutations in the primer grip of human immunodeficiency virus type 1 reverse transcriptase impair proviral DNA synthesis and virion maturation. Interestingly, assembly and maturation of mutant virus M230A were similar to those of the wild type, while mutants L234D and W239A showed impaired maturation. 1998 Journal of virology Abstract HIV L234D;M230A;W239A 115;55;125 120;60;130 9696874 Mutations in the primer grip of human immunodeficiency virus type 1 reverse transcriptase impair proviral DNA synthesis and virion maturation. The immature morphology of RT mutants L234D and W239A is due at least in part to premature cleavage of the gag-pol precursor, prior to virion budding, indicating that intracellular stability of Pr160(gag-pol) is of key importance during virus assembly. 1998 Journal of virology Abstract HIV L234D;W239A 38;48 43;53 GagPol;GagPol;PR;RT 107;200;194;27 114;207;196;29 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. Consistent with these observations, and from a mechanistic standpoint, both E89G-containing as well as doubly mutated RT had decreased dissociation constants from a complex consisting of RT and template-primer, in comparison with either wt RT or M184V-containing RT. 1998 The Journal of biological chemistry Abstract HIV E89G;M184V 76;246 80;251 RT;RT;RT;RT 118;187;240;263 120;189;242;265 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. In addition, certain mutations in RT that confer resistance to nucleoside analogs, such as M184V, are located near the polymerase active site. 1998 The Journal of biological chemistry Abstract HIV M184V 91 96 Pol;RT 119;34 129;36 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. Similar findings were obtained with the doubly mutated RT, although enzyme containing only the M184V mutation had lower processivity than wt. 1998 The Journal of biological chemistry Abstract HIV M184V 95 100 RT 55 57 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. The substitution of a glycine for glutamic acid at position 89 in human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT) (E89G) confers resistance to several nucleoside and non-nucleoside inhibitors of RT. 1998 The Journal of biological chemistry Abstract HIV E89G;E89G 133;22 137;62 RT;RT;RT 105;128;213 126;130;215 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. Thus, the E89G substitution is a dominant determinant in regard to each of the koff values from an RT.template/primer complex, RT processivity, and specific patterns of pausing during DNA polymerization. 1998 The Journal of biological chemistry Abstract HIV E89G 10 14 RT;RT 99;127 101;129 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. To characterize further these substitutions, we performed processivity assays alongside an analysis of pausing profiles with wild-type (wt) RT and recombinant RTs containing substitutions at E89G, M184V, or both. 1998 The Journal of biological chemistry Abstract HIV E89G;M184V 191;197 195;202 RT;RT 140;159 142;162 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. Viruses containing the E89G mutation synthesized longer strand DNA products than either wt viruses or viruses containing only the M184V mutation in endogenous RT assays. 1998 The Journal of biological chemistry Abstract HIV E89G;M184V 23;130 27;135 RT 159 161 9705331 Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing. We now show that E89G RT has higher processivity than wt enzyme as well as a different pattern of pausing sites. 1998 The Journal of biological chemistry Abstract HIV E89G 17 21 RT 22 24 9718121 Impaired fitness of foscarnet-resistant strains of human immunodeficiency virus type 1. In replication kinetics assays, the recombinant strains HX89K, HX92I, and HX156A (encoding RT mutations E89K, L92I, and S156A, respectively, in the HXB2-D genetic background) replicated to lower titers than the wild-type parent in the absence of drug, and the degree of replication impairment increased as PFA resistance increased. 1998 AIDS research and human retroviruses Abstract HIV E89K;L92I;S156A 104;110;120 108;114;125 RT 91 93 9718121 Impaired fitness of foscarnet-resistant strains of human immunodeficiency virus type 1. PFA-resistant strains LAI 92I and LAI 156A (encoding RT mutations L92I and S156A, respectively) were replication impaired in comparison to the wild-type parent LAI to a similar degree as observed for strains in the HXB2D background. 1998 AIDS research and human retroviruses Abstract HIV L92I;S156A 66;75 70;80 RT 53 55 9718121 Impaired fitness of foscarnet-resistant strains of human immunodeficiency virus type 1. These results show that the RT mutations E89K, L92I and S156A, observed in PFA-resistant strains selected in cell culture, reduce replication competence. 1998 AIDS research and human retroviruses Abstract HIV E89K;L92I;S156A 41;47;56 45;51;61 RT 28 30 9742239 The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency. In an effort to investigate the basis for this discrepancy, we have examined whether the increases in misinsertion fidelity observed for E89G and M184V RTs are accompanied by an increase in mispair extension fidelity. 1998 Nucleic acids research Abstract HIV E89G;M184V 137;146 141;151 RT 152 155 9742239 The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency. The relative efficiencies with which the wild type, E89G, M184V and M184V/E89G HIV-1 RTs extend model template-primer duplexes containing 3'-OH terminal mismatches were measured. 1998 Nucleic acids research Abstract HIV E89G;E89G;M184V;M184V 74;52;58;68 78;56;63;73 RT 85 88 9742239 The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency. These results suggest that amino acid substitutions that increase the fidelity of dNTP insertion do not necessarily increase misextension fidelity, and that the decreased misextension fidelity may counterbalance the increases in misinsertion fidelity observed for E89G and M184V RTs. 1998 Nucleic acids research Abstract HIV E89G;M184V 264;273 268;278 RT 279 282 9742239 The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency. Two nucleoside analog resistance mutations in HIV-1 reverse transcriptase (RT), E89G and M184V, were previously shown to increase the dNTP insertion fidelity of HIV-1 RT. 1998 Nucleic acids research Abstract HIV E89G;M184V 80;89 84;94 RT;RT;RT 52;75;167 73;77;169 9748354 Pyrimidine thioethers: a novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV. A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. 1998 Journal of medicinal chemistry Abstract HIV P236L 195 200 RT;RT;RT 114;137;148 135;139;150 9748354 Pyrimidine thioethers: a novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. 1998 Journal of medicinal chemistry Abstract HIV P236L 242 247 RT 248 250 9753473 Drug-resistant HIV-1 proteases identify enzyme residues important for substrate selection and catalytic rate. Crystal structures of the RSV PR R10K, I44V, I71V, and Il08V mutant enzymes presented here indicate that each of these substitutions has little effect on the overall structure of the respective enzymes. 1998 Biochemistry Abstract HIV I44V;I71V;R10K 39;45;33 43;49;37 PR 30 32 9753473 Drug-resistant HIV-1 proteases identify enzyme residues important for substrate selection and catalytic rate. In a parallel study, the individual mutations R10K, L12V, I44V, A60M, I71V, and I108V were introduced into RSV PR. 1998 Biochemistry Abstract HIV A60M;I108V;I44V;I71V;L12V;R10K 64;80;58;70;52;46 68;85;62;74;56;50 PR 111 113 9753473 Drug-resistant HIV-1 proteases identify enzyme residues important for substrate selection and catalytic rate. Mutants containing R8K, V32I, V82T, I84V, G48V/L90M, or V82T/I84V substitutions were analyzed for differences in substrate preference and catalytic efficiency using a set of single amino acid substituted HIV-1 CA-NCa cleavage site peptides. 1998 Biochemistry Abstract HIV G48V;I84V;I84V;L90M;R8K;V32I;V82T;V82T 42;36;61;47;19;24;30;56 46;40;65;51;22;28;34;60 Capsid 210 212 9753473 Drug-resistant HIV-1 proteases identify enzyme residues important for substrate selection and catalytic rate. Only the R8K and V32I mutants showed significant differences in subsite selection compared to wild-type enzyme. 1998 Biochemistry Abstract HIV R8K;V32I 9;17 12;21 9753473 Drug-resistant HIV-1 proteases identify enzyme residues important for substrate selection and catalytic rate. The RSV R10K substitution significantly altered substrate specificity and catalytic rate, compared to wild-type, in a manner similar to that of the HIV-1 R8K mutant. 1998 Biochemistry Abstract HIV R10K 8 12 9756769 Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Although the appearance of D30N was occasionally associated with concurrent or sequential emergence of other changes (e.g., at residues 35, 36, 46, 71, 77, and 88), genotypic changes associated with phenotypic resistance to other protease inhibitors were not observed (e.g., at residues 48, 50, 82, and 84) or were only rarely observed (e.g., at residue 90). 1998 Antimicrobial agents and chemotherapy Abstract HIV D30N 27 31 PR 230 238 9756769 Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Nucleotide sequence analysis of protease genes from plasma HIV type 1 (HIV-1) RNA revealed a unique aspartic acid (D)-to-asparagine (N) substitution at residue 30 (D30N) in 25 of 55 patients treated with nelfinavir for a median of 13 weeks. 1998 Antimicrobial agents and chemotherapy Abstract HIV D30N 164 168 PR 32 40 9756769 Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Similar results were observed in phenotypic assays utilizing HIV-1 NL4-3, which contained the D30N substitution alone or in combination with substitutions at other residues (e.g., residues 46, 71, and 88). 1998 Antimicrobial agents and chemotherapy Abstract HIV D30N 94 98 9760256 Implication of the tRNA initiation step for human immunodeficiency virus type 1 reverse transcriptase in the mechanism of 3'-azido-3'-deoxythymidine (AZT) resistance. A pre-steady-state kinetic analysis was used to examine the binding and incorporation of 2'-deoxythymidine 5'-triphosphate (dTTP) and 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) by wild-type HIV-1 reverse transcriptase and a clinically important AZT-resistant mutant form of the enzyme (D67N, K70R, T215Y, K219Q) utilizing a physiologically relevant RNA 18-mer/RNA 36-mer primer-template substrate. 1998 Biochemistry Abstract HIV D67N;K219Q;K70R;T215Y 294;313;300;306 298;318;304;311 RT 204 225 9765445 Analysis of pol gene heterogeneity, viral quasispecies, and drug resistance in individuals infected with group O strains of human immunodeficiency virus type 1. A Gly98 to Glu RT substitution identified in the treated patient suggests a possible reversion of a nonnucleoside RT inhibitor-resistant phenotype. 1998 Journal of virology Abstract HIV G98E 2 14 RT;RT 15;114 17;116 9765445 Analysis of pol gene heterogeneity, viral quasispecies, and drug resistance in individuals infected with group O strains of human immunodeficiency virus type 1. Amino acid substitutions (i.e., Phe-77 to Leu, Lys-101 to Glu, and Val-106 to Iso) associated with antiretroviral resistance were identified in RT clones from HIV-1 group O-infected patients not subjected to drug therapy or treated with unrelated drugs. 1998 Journal of virology Abstract HIV F77L 32 45 RT 144 146 9765445 Analysis of pol gene heterogeneity, viral quasispecies, and drug resistance in individuals infected with group O strains of human immunodeficiency virus type 1. Antiretroviral treatment also selected for specific substitutions, M184V and T215Y in the RT coding region, conferring resistance to 3'-dideoxy-3'-thiacytidine and zidovudine, respectively. 1998 Journal of virology Abstract HIV M184V;T215Y 67;77 72;82 RT 90 92 9768622 Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients. HIV-1 resistance to ATV was detected in 41% of patients and was most commonly associated with RT mutations K103N and Y181C. 1998 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV K103N;Y181C 107;117 112;122 RT 94 96 9768622 Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients. In contrast, the Y181C mutation was not detected in ATV-resistant isolates obtained from patients enrolled in ACTG 199, a study of ATV given in combination with zidovudine. 1998 Journal of acquired immune deficiency syndromes and human retrovirology Abstract HIV Y181C 17 22 9779795 Predicting structural effects in HIV-1 protease mutant complexes with flexible ligand docking and protein side-chain optimization. Flexible ligand docking and optimization of mobile protein side-chains have been performed to predict structural effects in the V32I/I47V/V82I HIV-1 protease mutant bound with the SB203386 ligand and in the V82A HIV-1 protease mutant bound with the A77003 ligand. 1998 Proteins Abstract HIV I47V;V32I;V82I;V82A 133;128;138;207 137;132;142;211 PR;PR 149;218 157;226 9780274 Resistance mutations in protease and reverse transcriptase genes of human immunodeficiency virus type 1 isolates from patients with combination antiretroviral therapy failure. The most commonly observed PR mutations were L10I, V82A/T/F, and L90M. 1998 The Journal of infectious diseases Abstract HIV L10I;L90M;V82A;V82F;V82T 45;65;51;51;51 49;69;59;59;59 PR 27 29 9790666 Counteracting HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with XV638 and SD146, cyclic urea amides with broad specificities. We now report the structures of the three active-site mutant proteases V82F, I84V, and V82F/I84V in complex with XV638 and SD146, two P2 analogues of DMP323 that are 8-fold more potent against the wild type and are able to inhibit a broad panel of drug-resistant variants [Jadhav, P. 1998 Biochemistry Abstract HIV I84V;I84V;V82F;V82F 77;92;71;87 81;96;75;91 PR 61 70 9797252 Coresistance to zidovudine and foscarnet is associated with multiple mutations in the human immunodeficiency virus type 1 reverse transcriptase. Six of these mutations were nonpolymorphic (T39A, V108I, K166R, K219R, K223Q, and L228R). 1998 Antimicrobial agents and chemotherapy Abstract HIV K166R;K219R;K223Q;L228R;T39A;V108I 57;64;71;82;44;50 62;69;76;87;48;55 9811701 Mutational analysis of residues in the coiled-coil domain of human immunodeficiency virus type 1 transmembrane protein gp41. We found that mutations of leucine to arginine or glutamic acid in position 556 and of alanine to arginine in position 558 resulted in undetectable levels of Env expression. 1998 Journal of virology Abstract HIV A558R 87 122 Env 158 161 9813120 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. Gly190Glu) when compared with other non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, alpha-APA and TIBO. 1998 Journal of molecular biology Abstract HIV G190E 0 9 NNRTI;RT 66;51 72;53 9813120 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. Loss of important protein-inhibitor interactions may account for the reduced potency of HBY 097 against the Tyr188Leu HIV-1 RT mutant. 1998 Journal of molecular biology Abstract HIV Y188L 108 117 RT 124 126 9813120 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex. 1998 Journal of molecular biology Abstract HIV Y188L 137 146 RT 153 155 9813120 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HBY 097 at 3.3 A resolution. 1998 Journal of molecular biology Abstract HIV Y188L 40 49 RT 56 58 9814869 Multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 strains isolated from patients from different European countries. A new mutation, S68G, was frequently associated with MddNR. 1998 AIDS (London, England) Abstract HIV S68G 16 20 9814869 Multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 strains isolated from patients from different European countries. DESIGN AND METHODS: Blood samples from patients after > or = 6 months of treatment with multiple ddN were screened for the MddNR mutation Q151M. 1998 AIDS (London, England) Abstract HIV Q151M 138 143 9814869 Multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 strains isolated from patients from different European countries. Viruses typically contained amino acid substitutions V75F, F77L, F116Y and Q151M in the RT gene. 1998 AIDS (London, England) Abstract HIV F116Y;F77L;Q151M;V75F 65;59;75;53 70;63;80;57 RT 88 90 9818151 Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors. The nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851 were selected as our next generation of cyclic urea HIV protease inhibitors because they achieve 8 h trough blood levels in dog, with a 10 mg/kg dose, at or above the protein-binding-adjusted IC90 value for the worst single mutant--that containing the Ile84-->Val mutation. 1998 Chemistry & biology Abstract HIV I84V 308 319 PR 112 120 9819361 A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple nucleoside inhibitors. Known drug resistance mutations were also observed in these strains, with T215Y appearing in all strains. 1998 The Journal of clinical investigation Abstract HIV T215Y 74 79 9824322 Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120. Here we show that the D373K envelope protein is processed and incorporated into virus particles, but that D373K virions have no detectable infectivity (below 0.1% relative to wild type). 1998 AIDS research and human retroviruses Abstract HIV D373K;D373K 22;106 27;111 Env 28 36 9824322 Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120. We have introduced the same mutation into the HIV-1 isolate LAV-I(BRU), in which the mutation is denoted D373K. 1998 AIDS research and human retroviruses Abstract HIV D373K 105 110 9824322 Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120. When D373K and the wild-type envelope gene were cotransfected in 293 cells at a 4:1 ratio, the resultant infectivity of the HIV-1 supernatant was reduced more than 100-fold. 1998 AIDS research and human retroviruses Abstract HIV D373K 5 10 Env 29 37 9835502 Patterns of resistance and cross-resistance to human immunodeficiency virus type 1 reverse transcriptase inhibitors in patients treated with the nonnucleoside reverse transcriptase inhibitor loviride. The most common genotypic change was the K103N substitution. 1998 Antimicrobial agents and chemotherapy Abstract HIV K103N 41 46 9835502 Patterns of resistance and cross-resistance to human immunodeficiency virus type 1 reverse transcriptase inhibitors in patients treated with the nonnucleoside reverse transcriptase inhibitor loviride. The range of phenotypic resistance in samples containing the K103N substitution could not be predicted from a genotypic analysis of known NNRTI resistance-associated mutations. 1998 Antimicrobial agents and chemotherapy Abstract HIV K103N 61 66 NNRTI 138 143 9835502 Patterns of resistance and cross-resistance to human immunodeficiency virus type 1 reverse transcriptase inhibitors in patients treated with the nonnucleoside reverse transcriptase inhibitor loviride. The Y181C substitution was detected in one isolate which was resistant to loviride and delavirdine but sensitive to efavirenz, HBY-097, and tivirapine. 1998 Antimicrobial agents and chemotherapy Abstract HIV Y181C 4 9 9835523 An Escherichia coli expression assay and screen for human immunodeficiency virus protease variants with decreased susceptibility to indinavir. One substitution, W6R, is also frequently found by the screen and has not been reported elsewhere. 1998 Antimicrobial agents and chemotherapy Abstract HIV W6R 18 21 9835523 An Escherichia coli expression assay and screen for human immunodeficiency virus protease variants with decreased susceptibility to indinavir. The discovered HIV protease variants contain amino acid substitutions commonly associated with indinavir resistance in clinical isolates, including the substitutions L90M, L63P, I64V, V82A, L24I, and I54T. 1998 Antimicrobial agents and chemotherapy Abstract HIV I54T;I64V;L24I;L63P;L90M;V82A 200;178;190;172;166;184 204;182;194;176;170;188 PR 19 27 9835523 An Escherichia coli expression assay and screen for human immunodeficiency virus protease variants with decreased susceptibility to indinavir. The highly sensitive system detects the contributions of single substitutions such as I84V, L90M, and L63P. 1998 Antimicrobial agents and chemotherapy Abstract HIV I84V;L63P;L90M 86;102;92 90;106;96 9835523 An Escherichia coli expression assay and screen for human immunodeficiency virus protease variants with decreased susceptibility to indinavir. The L63P substitution, which is also associated with indinavir resistance, increases the stability of the isolated protease relative to that of the native HXB2 protease. 1998 Antimicrobial agents and chemotherapy Abstract HIV L63P 4 8 PR;PR 115;160 123;168 9837947 Functional analysis of amino acid residues constituting the dNTP binding pocket of HIV-1 reverse transcriptase. The K219A, Y115F, and Q151M mutants had no influence on the fidelity; Y183A, Y183F, K65A, and Q151N mutants exhibited higher fidelity on both RNA and DNA templates, while Y115A was less error-prone selectively on a DNA template. 1998 The Journal of biological chemistry Abstract HIV K219A;K65A;Q151M;Q151N;Y115A;Y115F;Y183A;Y183F 4;84;22;94;171;11;70;77 9;88;27;99;176;16;75;82 9840288 On the role of the second coding exon of the HIV-1 Tat protein in virus replication and MHC class I downregulation. Cell surface expression of the MHC protein was analyzed in T cells infected with the wild-type LAI virus and the replication-competent Q72stop mutant. 1998 AIDS research and human retroviruses Abstract HIV Q72X 135 142 9840288 On the role of the second coding exon of the HIV-1 Tat protein in virus replication and MHC class I downregulation. This Q72stop mutant displays reduced transcriptional activity of approximately 54% in transient LTR-CAT transfection assays. 1998 AIDS research and human retroviruses Abstract HIV Q72X 5 12 LTR 96 99 9840288 On the role of the second coding exon of the HIV-1 Tat protein in virus replication and MHC class I downregulation. To test the contribution of the second Tat-coding exon to virus replication, the Q72stop mutation was also introduced in the infectious pLAI molecular clone. 1998 AIDS research and human retroviruses Abstract HIV Q72X 81 88 Tat 39 42 9841827 Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro. Additionally, HIV from 8 patients developed the M184V RT mutation because of concomitant lamivudine use. 1999 The Journal of infectious diseases Abstract HIV M184V 48 53 RT 54 56 9841827 Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro. In growth kinetics studies, expression of the M184V RT mutation resulted in attenuated viral growth in peripheral blood mononuclear cell cultures. 1999 The Journal of infectious diseases Abstract HIV M184V 46 51 RT 52 54 9843396 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. The D67N/K70R/T215F/K219Q mutant showed an increased rate of pyrophosphorolysis (the reverse reaction of DNA synthesis) of chain-terminated DNA; this enhanced pyrophosphorolysis was due to the D67N/K70R mutations. 1998 Biochemistry Abstract HIV D67N;K219Q;K70R;T215F;D67N;K70R 4;20;9;14;193;198 8;25;13;19;197;202 9843396 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. The D67N/K70R/T215F/K219Q mutant showed increased DNA polymerase processivity; this resulted from decreased template/primer dissociation from RT, and was due to the T215F/K219Q mutations. 1998 Biochemistry Abstract HIV D67N;K219Q;K70R;T215F;K219Q;T215F 4;20;9;14;171;165 8;25;13;19;176;170 Pol;RT 54;142 64;144 9843396 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. The D67N/K70R/T215F/K219Q mutant was less sensitive to AZTTP (IC50 approximately 300 nM) than wt RT (IC50 approximately 100 nM) in the presence of 0.5 mM pyrophosphate. 1998 Biochemistry Abstract HIV D67N;K219Q;K70R;T215F 4;20;9;14 8;25;13;19 RT 97 99 9843396 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. The multiple mutations associated with high-level AZT resistance (D67N, K70R, T215F, K219Q) arise in two separate subdomains of the viral reverse transcriptase (RT), suggesting that these mutations may contribute differently to overall resistance. 1998 Biochemistry Abstract HIV D67N;K219Q;K70R;T215F 66;85;72;78 70;90;76;83 RT;RT 138;161 159;163 9843396 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. We compared wild-type RT with the D67N/K70R/T215F/K219Q, D67N/K70R, and T215F/K219Q mutant enzymes. 1998 Biochemistry Abstract HIV D67N;K219Q;K70R;T215F;D67N;K219Q;K70R;T215F 34;50;39;44;57;78;62;72 38;55;43;49;61;83;66;77 RT 22 24 9847302 Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein. Cotransfection experiments with Y36S-L41P and wild-type proviral DNAs revealed that the mutant Gag dominantly blocked the incorporation of Env by wild-type Gag. 1999 Journal of virology Abstract HIV L41P;Y36S 37;32 41;36 Env;Gag;Gag 139;95;156 142;98;159 9847302 Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein. However, one exception, Y36F, was 300-fold as infectious the wild type. 1999 Journal of virology Abstract HIV Y36F 24 28 9847302 Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein. In contrast to the single-substitution mutants, a virus with two substitutions in this region of p6(Gag), Y36S-L41P, could not infect susceptible cells. 1999 Journal of virology Abstract HIV L41P;Y36S 111;106 115;110 Gag;Gag 100;97 103;99 9847302 Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein. These results show that the Y36S-L41P p6(Gag) mutation dramatically blocks the incorporation of HIV-1 Env, presumably acting late in assembly and early during budding. 1999 Journal of virology Abstract HIV L41P;Y36S 33;28 37;32 Env;Gag;Gag 102;41;38 105;44;40 9847302 Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein. This mutant could be complemented with surface glycoproteins from vesicular stomatitis virus and murine leukemia virus, showing that the inability to incorporate Env was the lethal defect for the Y36S-L41P virus. 1999 Journal of virology Abstract HIV L41P;Y36S 201;196 205;200 Env 162 165 9852086 Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase. Recombinant viruses harboring the Y318F or Y318W mutation in the RT showed a similar resistance/sensitivity pattern to NNRTIs as their corresponding 318 mutant recombinant RTs. 1998 The Journal of biological chemistry Abstract HIV Y318F;Y318W 34;43 39;48 NNRTI;RT;RT 119;65;172 125;67;175 9852086 Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase. The Y318F mutant RT retained substantial sensitivity to the majority of NNRTIs tested, whereas the Y318W mutant RT showed varying degrees of resistance to NNRTIs. 1998 The Journal of biological chemistry Abstract HIV Y318F;Y318W 4;99 9;104 NNRTI;NNRTI;RT;RT 72;155;17;112 78;161;19;114 9852086 Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase. Using site-directed mutagenesis, six mutant RTs were constructed bearing the mutations Y318H, Y318K, Y318L, Y318C, Y318W, and Y318F. 1998 The Journal of biological chemistry Abstract HIV Y318C;Y318F;Y318H;Y318K;Y318L;Y318W 108;126;87;94;101;115 113;131;92;99;106;120 RT 44 47 9852086 Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase. We found that only the Y318W and Y318F mutant RTs retained substantial RT activity, whereas the catalytic activities of the Y318K, Y318C, Y318H, and Y318L RT mutants were less than 5% of the wild-type activity. 1998 The Journal of biological chemistry Abstract HIV Y318C;Y318F;Y318H;Y318K;Y318L;Y318W 131;33;138;124;149;23 136;38;143;129;154;28 RT;RT;RT 46;71;155 49;73;157 9865962 Solution structure of the His12 --> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium. In contrast to the wild-type domain, however, which exists in two interconverting conformational states arising from different modes of coordination of the two histidine side chains to the metal, the cadmium complex of the His12 --> Cys mutant exists in only a single form at low pH. 1998 Protein science Abstract HIV H12C 223 236 9865962 Solution structure of the His12 --> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium. The solution structure of His12 --> Cys mutant of the N-terminal zinc binding domain (residues 1-55; IN(1-55)) of HIV-1 integrase complexed to cadmium has been solved by multidimensional heteronuclear NMR spectroscopy. 1998 Protein science Abstract HIV H12C 26 39 IN;IN 120;101 129;103 9882317 Conserved cysteines of the human immunodeficiency virus type 1 protease are involved in regulation of polyprotein processing and viral maturation of immature virions. In support of this, C67A C95A virions processed Gag up to fivefold faster than wild-type virions in the absence of a reducing agent. 1999 Journal of virology Abstract HIV C67A;C95A 20;25 24;29 Gag 48 51 9882317 Conserved cysteines of the human immunodeficiency virus type 1 protease are involved in regulation of polyprotein processing and viral maturation of immature virions. To this end, we generated four HIV-1 molecular clones: the wild type, containing both cysteine residues; a protease mutant in which the cysteine at position 67 was replaced by an alanine (C67A); a C95A protease mutant; and a double mutant (C67A C95A). 1999 Journal of virology Abstract HIV C67A;C67A;C67A;C95A;C95A 188;240;136;197;245 192;245;186;201;249 PR;PR 107;202 115;210 9890944 A critical site in the core of the CCR5 chemokine receptor required for binding and infectivity of human immunodeficiency virus type 1. Conversely, the R163G mutant of AGM CCR5 was substantially strengthened as a coreceptor for HIV-1 and had improved R5 gp120 binding affinity relative to the wild-type AGM CCR5. 1999 The Journal of biological chemistry Abstract HIV R163G 16 21 gp120 118 123 9890944 A critical site in the core of the CCR5 chemokine receptor required for binding and infectivity of human immunodeficiency virus type 1. Whereas 2D7 antibody binding to CCR5 was unaffected by the G163R mutation, it was prevented by a conservative ECL2 substitution (K171R), shared between rhesus and AGM CCR5s. 1999 The Journal of biological chemistry Abstract HIV K171R 129 134 9925514 Genetic variation and susceptibilities to protease inhibitors among subtype B and F isolates in Brazil. and Brazilian subtype B consensus in eight positions (I15V, E35D, M36I, R41K, R57K, Q61N, L63P, and L89M). 1999 Antimicrobial agents and chemotherapy Abstract HIV E35D;I15V;L63P;L89M;M36I;Q61N;R41K;R57K 60;54;90;100;66;84;72;78 64;58;94;104;70;88;76;82 9925514 Genetic variation and susceptibilities to protease inhibitors among subtype B and F isolates in Brazil. The frequency of critical PI resistance substitutions (amino acid changes D30N, V82A/F/T, I84V, N88D, and L90M) among Brazilian isolates is very low (mean, 2.5%), and the associated secondary substitutions (amino acid positions 10L, 20K, 36M, 46M, 48G, 54I, 63P, 71A, and 77A) are infrequent. 1999 Antimicrobial agents and chemotherapy Abstract HIV D30N;I84V;L90M;N88D;V82A;V82F;V82T 74;90;106;96;80;80;80 78;94;110;100;88;88;88 PI 26 28 9925516 A rapid non-culture-based assay for clinical monitoring of phenotypic resistance of human immunodeficiency virus type 1 to lamivudine (3TC). Mixing experiments showed a detection threshold of 10% 3TC-resistant virus (M184V) in a background of WT HIV-1. 1999 Antimicrobial agents and chemotherapy Abstract HIV M184V 76 81 9925516 A rapid non-culture-based assay for clinical monitoring of phenotypic resistance of human immunodeficiency virus type 1 to lamivudine (3TC). Under our assay conditions, we found that 5 microM 3TC-TP inhibited RT activity from wild-type (WT), zidovudine-resistant, or nevirapine-resistant HIV-1 but not from HIV-1 carrying either the M184V mutation or multidrug (MD) resistance mutations (77L/116Y/151M or 62V/75I/77L/116Y/151M). 1999 Antimicrobial agents and chemotherapy Abstract HIV M184V 192 197 RT 68 70 9927728 Molecular basis for the enantioselectivity of HIV-1 reverse transcriptase: role of the 3'-hydroxyl group of the L-(beta)-ribose in chiral discrimination between D- and L-enantiomers of deoxy- and dideoxy-nucleoside triphosphate analogs. The results showed that the 3'-hydroxyl group of the L-(beta)-2'-deoxyribose moiety caused an unfavourable steric hindrance with critic residues in the HIV-1 RT active site and this steric barrier was increased by the Y181I mutation. 1999 Nucleic acids research Abstract HIV Y181I 218 223 RT 158 160 9952382 Codon 215 mutations in human immunodeficiency virus-infected pregnant women. Swiss Collaborative 'HIV and Pregnancy' Study. Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine. 1999 The Journal of infectious diseases Abstract HIV T215F;T215Y 34;34 41;41 9952383 Antiviral activity of the human immunodeficiency virus type 1-specific nonnucleoside reverse transcriptase inhibitor HBY 097 alone and in combination with zidovudine in a phase II study. HBY 097/2001 Study Group. Fewer patients receiving combination therapy with high-dose HBY 097 developed the K103N variant (P<.01). 1999 The Journal of infectious diseases Abstract HIV K103N 82 87 9952383 Antiviral activity of the human immunodeficiency virus type 1-specific nonnucleoside reverse transcriptase inhibitor HBY 097 alone and in combination with zidovudine in a phase II study. HBY 097/2001 Study Group. Genotypic analysis of resistance development revealed reverse transcriptase K103N variants in most patients, which was associated with less durable efficacy of HBY 097 treatment. 1999 The Journal of infectious diseases Abstract HIV K103N 76 81 RT 54 75 9973178 Biochemical characterization of HIV-1 reverse transcriptases encoding mutations at amino acid residues 161 and 208 involved in resistance to phosphonoformate. (TIBO R82150), the mutant RTs Q161L and Q161L/H208Y were resistant to 3'-azido-3'-deoxythymidine triphosphate (AZTTP) and as susceptible as the wt enzyme to Nevirapine and TIBO R82150. 1998 Biochemical pharmacology Abstract HIV H208Y;Q161L;Q161L 46;30;40 51;35;45 RT 26 29 9973178 Biochemical characterization of HIV-1 reverse transcriptases encoding mutations at amino acid residues 161 and 208 involved in resistance to phosphonoformate. Like the wild-type (wt) enzyme, mutant rRTs H208Y and Q161L/H208Y showed a preference for Mg2+ over Mn2+, whereas the Q161L rRT preferred Mn2. 1998 Biochemical pharmacology Abstract HIV H208Y;H208Y;Q161L;Q161L 60;44;54;118 65;49;59;123 9973178 Biochemical characterization of HIV-1 reverse transcriptases encoding mutations at amino acid residues 161 and 208 involved in resistance to phosphonoformate. Mutations at amino acid residues 161 (Q161L) and 208 (H208Y) of the reverse transcriptase (RT) have been identified in HIV-1 variants which are resistant to phosphonoformate (PFA). 1998 Biochemical pharmacology Abstract HIV H208Y;Q161L 54;38 59;43 RT;RT 68;91 89;93 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Another nonsynonymous mutation, AGA to GGA (R264G), has not been detected in patients, but was engineered into the LAI strain of HIV. 2001 The Journal of experimental medicine Introduction HIV R264G 44 49 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. argued that R264G should be preferentially selected if CTLs exerted a significant selection pressure on the virus 14. 2001 The Journal of experimental medicine Introduction HIV R264G 12 17 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In two previously described patients, the mutation K (AAA) for R (AGA) at residue 264 (R264K) occurred late in the infection and coincided with disease progression 7. 2001 The Journal of experimental medicine Introduction HIV R264K 87 92 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Substitution of either lysine (K) or glycine (G) for arginine (R) at gag residue 264 (R264K and R264G) results in an epitope that binds poorly to HLA-B2705, thus forming unstable complexes 7 14. 2001 The Journal of experimental medicine Introduction HIV R264G;R264K 96;86 101;92 Gag 69 72 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. The interaction of the arginine (R) residue at position 2 of this and other HLA-B2705-restricted epitopes with the B pocket of the HLA-B2705 plays a crucial role in stabilizing the MHC-peptide complexes 9 10 11 12 13. 2001 The Journal of experimental medicine Introduction HIV R2R 20 60 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Furthermore, amongst a series of NRTI-resistant HIV-1 RT variants, only the K65R RT mutant displayed a significant (5-fold) level of resistance to RT1t49. 2005 AIDS research and therapy Introduction HIV K65R 76 80 NRTI;RT;RT 33;54;81 37;56;83 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. In order to address this notion, we previously used a phenotypic screen based on the in situ detection of RNA-dependent DNA polymerase activity of HIV-1 RT expressed within bacterial colonies, and isolated two variants of recombinant HIV-1 RT bearing the substitutions N255D or N265D, both of which displayed in vitro resistance to the DNA aptamer RT1t49. 2005 AIDS research and therapy Introduction HIV N255D;N265D 269;278 274;283 Pol;RT;RT 124;153;240 134;155;242 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. In support of this view, we have further demonstrated that all three mutants (the N255D, N265D and the double mutant (Dbl) RTs containing both mutations) are defective for processive DNA-dependent DNA polymerase activity (DDDP), although N265D retained processive polymerization activity on RNA templates. 2005 AIDS research and therapy Introduction HIV N255D;N265D;N265D 82;89;238 87;94;243 Pol;RT 201;123 211;126 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Alteration of each of the three sequences such as Q214L/Q216L, K215A/K219A, W235E, K236A/K240A, K244A/E246A, RRE263-5AAH resulted in loss of viral replication. 2005 Retrovirology Introduction HIV E246A;K215A;K219A;K236A;K240A;K244A;Q214L;Q216L;W235E 102;63;69;83;89;96;50;56;76 107;68;74;88;94;101;55;61;81 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. However, in attempt to analyze the effect of these mutants during HIV-1 replication, other studies did not reveal the importance of these IN mutants (K186Q and Q214/216L) for viral nuclear import; rather they appear to be required for reverse transcription, integration or undefined post-nuclear entry steps. 2005 Retrovirology Introduction HIV K186Q 150 156 RT;IN 235;138 256;140 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Previous report has suggested an atypical bipartite NLS (186KRK and 211KELQKQITK) by showing that IN mutants K186Q and Q214/216L in these regions lost the protein nuclear localization and their inability to bind to karyopherin alpha in vitro . 2005 Retrovirology Introduction HIV K186Q 109 114 IN 98 100 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. have examined the most severely affected mutant in this set, F61W, for its effect on the melting of the +2 and +3 using the permanganate sensitivity assay. 2006 Nucleic acids research Introduction HIV F61W 61 65 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In other words, substitutions with maximal stabilization, such as F61W led to minimal strand displacement, while those that did not stabilize the terminal base pair ahead of the active site were maximally active in strand displacement synthesis (e.g. 2006 Nucleic acids research Introduction HIV F61W 66 70 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In the present study, we have investigated the effect of substitutions F61L, F61W, F61Y and F61A on HIV replication. 2006 Nucleic acids research Introduction HIV F61A;F61L;F61W;F61Y 92;71;77;83 96;75;81;87 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In vitro studies were performed to evaluate whether recombinant mutant RTs display RNase H defects, which showed that F61Y RT was indeed defective in RNase H-mediated removal of PPT RNA from plus DNA, while F61A was defective for both the generation of PPT RNA primer and its removal. 2006 Nucleic acids research Introduction HIV F61A;F61Y 207;118 211;122 RT;RT 71;123 74;125 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Since the formation of 5'-LTR is accomplished via strand displacement synthesis, we analyzed 2-LTR circle junctions, as surrogate for linear viral DNA, from cells infected with the wild-type, F61L, F61W and F61Y mutants. 2006 Nucleic acids research Introduction HIV F61L;F61W;F61Y 192;198;207 196;202;211 LTR;LTR 26;95 29;98 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Those studies indeed confirm that F61W mutant is deficient in melting the two bases ahead of the active site. 2006 Nucleic acids research Introduction HIV F61W 34 38 16956392 HIV-2 Protease resistance defined in yeast cells. In a recent report, where five primary HIV-2 isolates obtained from two different infected individuals at different time points were tested for PI activity, it has been shown that neither I36V, V46I nor V71L modified the susceptibility of HIV-2 Protease to PIs. 2006 Retrovirology Introduction HIV I36V;V46I;V71L 188;194;203 192;198;207 PR;PI;PI 245;144;257 253;146;260 16956392 HIV-2 Protease resistance defined in yeast cells. Nevertheless, the few reported data establish that i) the natural nucleotide polymorphism of the HIV-2 Protease includes amino acid substitutions that are associated with drug resistance in HIV-1, and ii) comparison between the Protease sequences of treated and untreated HIV-2 infected individuals reveals a number of mutations under some PI-selective pressure such as K7R, V20I/A, I36V, V46I, I54L/M, V62A/T, V71L, I82F, I84V/L, 90LM, and L99F. 2006 Retrovirology Introduction HIV I36V;I54L;I54M;I82F;I84L;I84V;K7R;L99F;V20A;V20I;V46I;V62A;V62T;V71L 383;395;395;417;423;423;370;441;375;375;389;403;403;411 387;401;401;421;429;429;373;445;381;381;393;409;409;415 PR;PR;PI 103;228;340 111;236;342 16956392 HIV-2 Protease resistance defined in yeast cells. Results, obtained from functional test on the ability of those PI to inhibit viral replication showed that amino acid substitutions such as : T12P, G17Q, R72A, M76V, I54M, I82F, V47A, K45R confer a resistant phenotype. 2006 Retrovirology Introduction HIV G17Q;I54M;I82F;K45R;M76V;R72A;T12P;V47A 148;166;172;184;160;154;142;178 152;170;176;188;164;158;146;182 PI 63 65 17192195 Generation and characterization of a stable cell population releasing fluorescent HIV-1-based Virus Like Particles in an inducible way. In this regard, it was recently demonstrated that the Nef palmitoylation produced by mutating the Gly 3 to Cys increases the raft localization up to 12-fold compared with wt Nef. 2006 BMC biotechnology Introduction HIV G3C 98 110 Nef;Nef 54;174 57;177 17192195 Generation and characterization of a stable cell population releasing fluorescent HIV-1-based Virus Like Particles in an inducible way. This was indeed the case of the HIV-1 Nef double mutant V153L, E177G we recently described, whose strong raft localization leads to a virion incorporation about 100-fold more efficient than its wt counterpart. 2006 BMC biotechnology Introduction HIV E177G;V153L 63;56 68;61 Nef 38 41 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Because there are some important differences in the amino acid sequence of HIV-1 and SIV RT which affect susceptibilities and the mutational patterns to antiviral drugs, it is unclear to what extent these findings from the SIV model regarding the in vivo emergence, virulence and clinical implications of K65R viral mutants during tenofovir treatment can be extrapolated to HIV-1 RT. 2007 Retrovirology Introduction HIV K65R 305 309 RT;RT 89;380 91;382 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Further experiments in one animal that suppressed K65R viremia to undetectable levels demonstrated that, similarly to the findings in the SIVmac251 model, both CD8+ cell-mediated antiviral immune responses and continued tenofovir therapy were important to obtain maximal suppression of RT-SHIV viremia. 2007 Retrovirology Introduction HIV K65R 50 54 RT 286 288 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Further experiments, using in vivo CD8+ cell depletions and treatment interruption, revealed that this suppression of K65R viremia depended on strong CD8+ cell-mediated immune responses, but that continued tenofovir therapy was also still necessary. 2007 Retrovirology Introduction HIV K65R 118 122 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. However, a lower virologic success rate has been observed when tenofovir was used in specific combinations with other drugs with overlapping resistance profile (e.g., lamivudine, didanosine and abacavir), and the K65R mutation was found in approximately 50% of patients with a less-than-desired virologic response on such regimens. 2007 Retrovirology Introduction HIV K65R 213 217 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. However, even when K65R viremia was not suppressed, continued tenofovir treatment was, surprisingly, associated with clinical benefits (i.e., disease-free survival) that were larger than predicted based on viral RNA levels and standard immune markers. 2007 Retrovirology Introduction HIV K65R 19 23 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. In the absence of tenofovir treatment, these K65R SIV isolates replicated in vivo to high levels and induced a disease course indistinguishable from that of wild-type virus. 2007 Retrovirology Introduction HIV K65R 45 49 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. In the presence of tenofovir treatment, however, disease-free survival was improved significantly, and some animals were able to suppress viremia of K65R virus to low or undetectable levels for 4 to more than 10 years. 2007 Retrovirology Introduction HIV K65R 149 153 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. It is also unclear whether the detection of K65R HIV-1 mutants is a valid criterion for withdrawing tenofovir from the patient's regimen, as it is possible that tenofovir still exerts some residual antiviral activity in vivo against replication of K65R HIV-1. 2007 Retrovirology Introduction HIV K65R;K65R 44;248 48;252 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Many tenofovir-containing regimens induce strong and long-lasting suppression of viremia in the majority of persons, with a low occurrence of the K65R mutation; the emergence of K65R mutants in such patients was not always associated with a viral rebound. 2007 Retrovirology Introduction HIV K65R;K65R 146;178 150;182 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Prolonged tenofovir monotherapy of macaques infected with virulent SIVmac251 resulted in the emergence of mutants with the K65R mutation in RT. 2007 Retrovirology Introduction HIV K65R 123 127 RT 140 142 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Tenofovir (9-[2-(phosphonomethoxy)propyl]adenine; PMPA) is a commonly used antiretroviral compound which selects for the K65R mutation in reverse transcriptase (RT); this mutation is associated with a 2- to 5-fold reduced in vitro susceptibility to tenofovir. 2007 Retrovirology Introduction HIV K65R 121 125 RT;RT 138;161 159;163 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The current report is the first one to demonstrate that during prolonged tenofovir therapy, RT-SHIV infected animals developed first K70E mutants, which were then replaced by K65R mutants. 2007 Retrovirology Introduction HIV K65R;K70E 175;133 179;137 RT 92 94 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. This is also true for K65R viral mutants. 2007 Retrovirology Introduction HIV K65R 22 26 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. This suggests that maintaining tenofovir as part of HAART, particularly when CD8+ cell-mediated immune responses are good and no better therapies are available, may still offer clinical benefits to persons infected with K65R mutants. 2007 Retrovirology Introduction HIV K65R 220 224 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Thus, a long-term study was performed to address the following questions through sequential experiments: (i) does in vivo passage of RT-SHIV lead to higher or more consistent virulence, (ii) does prolonged tenofovir treatment initiated during chronic RT-SHIV infection lead to the emergence of K65R viral mutants, (iii) what are the clinical implications of K65R mutants, and (iv) what is the role of CD8+ cells and continued tenofovir treatment in controlling viremia of K65R RT-SHIV? 2007 Retrovirology Introduction HIV K65R;K65R;K65R 294;358;472 298;362;476 RT;RT;RT 133;251;477 135;253;479 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Thus, a long-term study was performed to address the following questions through sequential experiments: (i) does in vivo passage of RT-SHIV lead to higher or more consistent virulence, (ii) does prolonged tenofovir treatment initiated during chronic RT-SHIV infection lead to the emergence of K65R viral mutants, (iii) what are the clinical implications of K65R mutants, and (iv) what is the role of CD8+ cells and continued tenofovir treatment in controlling viremia of K65R RT-SHIV. 2007 Retrovirology Introduction HIV K65R;K65R;K65R 294;358;472 298;362;476 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. While the K65R mutation reduces replication fitness of HIV-1 in vitro relative to wild-type virus, it is unclear to which extent this can be extrapolated to virus replication fitness in vivo, especially when K65R is accompanied by other mutations in RT; some mutations may be compensatory (to improve replicative capacity), while the combination of K65R with certain other drug-selected mutations may be deleterious for viral replicative capacity (e.g., L74V, certain thymidine-analogue mutations), or may restore viral susceptibility to other compounds of the drug regimen. 2007 Retrovirology Introduction HIV K65R;K65R;K65R;L74V 10;208;349;454 14;212;353;458 RT 250 252 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Since mutation of Asp51 to alanine has shown to be critical for proper capsid formation and subsequent replication of the virus, we extended the above findings and examined amino acid substitutions of this invariable residue to asparagine, glutamate, and glutamine. 2007 Retrovirology Introduction HIV D51A 18 34 Capsid;Asp 71;18 77;21 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. The study showed that mutation of Asp51 to alanine to be lethal. 2007 Retrovirology Introduction HIV D51A 34 50 Asp 34 37 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Two of the three mutants (D51E and D51N) were stable in vitro as was evidenced by forming highly polymerized capsid tubular structures that were closely resembling wild type structure, however, the infectivity and in vivo morphological structures of all three mutants were severely affected. 2007 Retrovirology Introduction HIV D51E;D51N 26;35 31;39 Capsid 109 115 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. We show that a variant of this epitope with an L to M substitution at position 6 (L6M) frequently arises as a CTL escape variant. 2007 The Journal of experimental medicine Introduction HIV L6M;L6M 82;47 85;80 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. In this animal model, the SP1/A1V mutant had viral replication and thymocyte depletion kinetics similar to WT HIV-1. 2007 PloS one Introduction HIV A1V 30 33 SP1 26 29 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Finally, a recent study reported that A371V in the connection domain and Q509L in the RNase H domain of HIV-1 RT were selected in combination with TAMs when virus was passaged under increasing concentrations of AZT. 2007 PLoS medicine Introduction HIV A371V;Q509L 38;73 43;78 RT 110 112 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In addition to changes in the connection domain, the mutations H539N and D549N in the RNase H domain have been shown to increase AZT resistance in a WT genetic background and in combination with TAMs. 2007 PLoS medicine Introduction HIV D549N;H539N 73;63 78;68 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In this study, we evaluated the in vivo relevance and role in drug resistance of a common RT connection domain mutation, N348I, using a variety of complementary approaches. 2007 PLoS medicine Introduction HIV N348I 121 126 RT 90 92 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Mutational studies revealed the presence of several connection domain mutations, including E312Q, G335C/D, N348I, A360I/V, V365I, and A376S, that were associated with AZT resistance. 2007 PLoS medicine Introduction HIV A360I;A360V;A376S;E312Q;G335C;G335D;N348I;V365I 114;114;134;91;98;98;107;123 121;121;139;96;105;105;112;128 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The impact of N348I on decreased susceptibility to AZT and NNRTIs was determined in cell culture-based assays and further confirmed in biochemical studies with recombinant RT. 2007 PLoS medicine Introduction HIV N348I 14 19 NNRTI;RT 59;172 65;174 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The prevalence of N348I was evaluated in treated versus therapy-naive individuals; its order of appearance relative to other drug resistance mutations was determined; and its association with virological failure was compared with other TAMs. 2007 PLoS medicine Introduction HIV N348I 18 23 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. These include the G333D/E polymorphism that facilitates dual AZT/3TC resistance in viruses that contain both thymidine analogue mutations (TAMs) and M184V and the Y318F mutation that confers NNRTI resistance. 2007 PLoS medicine Introduction HIV G333D;G333E;M184V;Y318F 18;18;149;163 25;25;154;168 NNRTI 191 196 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. We have shown recently that four point mutations involving the amino acids 211 (K211I), 224 (I224T) 345 (S345T) and 350 (E350K) located in the PR-RT gene are involved in AZT resistance of SFVmac. 2008 Nucleic acids research Introduction HIV E350K;I224T;K211I;S345T 121;93;80;105 126;98;85;110 PR;RT 143;146 145;148 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. In this study we genetically characterized protease inhibitor resistant variants carrying the protease L90M mutation before they reached readily detectable frequencies. 2008 Retrovirology Introduction HIV L90M 103 107 PR;PR 43;94 51;102 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. L90M allele specific amplification and sequencing of the resulting PCR product allowed us to compare an upstream linked region of early minority L90M variants with those of co-replicating dominant L90 viruses and to the L90M viruses which later came to dominate the plasma quasispecies. 2008 Retrovirology Introduction HIV L90M;L90M;L90M 145;220;0 149;224;4 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. L90M is one of the most common protease-inhibitor resistance mutations and is selected primarily by the protease-inhibitors saquinavir, nelfinavir, and indinavir, at least one of which was received by each of the patients in this study. 2008 Retrovirology Introduction HIV L90M 0 4 PR;PR 31;104 39;112 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Primary drug resistance mutations that alone confers moderate resistance such as V82A and L90M are initially selected followed by the addition of secondary mutations often located outside of the active site of the PR, such as L10I, M36I, M46I, L63P, or A71V leading to higher levels of resistance. 2008 Retrovirology Introduction HIV A71V;L10I;L63P;L90M;M36I;M46I;V82A 253;226;244;90;232;238;81 257;230;248;94;236;242;85 PR 214 216 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The L90M mutation, which is not located near the enzyme' s active site, is thought to displaces L24, which is adjacent to the catalytic residue D25, reducing the volume of the substrate cleft or protease dimer stability decreasing susceptibility to most protease inhibitors. 2008 Retrovirology Introduction HIV L90M 4 8 PR;PR 195;254 203;262 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Using Bayesian evolutionary analysis to sample alternative phylogenetic trees we determined that in a significant fraction of patients the early and later L90M carrying variants appear to have distinct origins, and therefore to have been originally selected on different genetic backbones. 2008 Retrovirology Introduction HIV L90M 155 159 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Both changes are particularly interesting since they are located in close proximity of the known M41L drug resistance mutation. 2008 Retrovirology Introduction HIV M41L 97 101 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. HIV-1 develops these TAMs by two distinct pathways: the TAM-1 pathway consisting of T215Y, M41L, L210W and sometimes D67N or the TAM-2 pathway including T215F, K70R, K219Q/E and D67N. 2008 Retrovirology Introduction HIV D67N;D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 117;178;166;166;160;97;91;153;84 121;182;173;173;164;102;95;158;89 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. In this study we have investigated which mechanisms explain the appearance of the E40F and K43E substitutions during NRTI-treatment by generating a panel of site directed mutants and analysing their replication capacity as well as their drug sensitivities. 2008 Retrovirology Introduction HIV E40F;K43E 82;91 86;95 NRTI 117 121 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Multiple studies have identified mutations at (at least) six codons in the reverse transcriptase (RT) enzyme (thymidine analogue associated mutations (TAMs); M41L, D67N, K70R, L210W, T215Y/F and K219Q/E) that can cause a decrease in Zidovudine susceptibility. 2008 Retrovirology Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 164;195;195;170;176;158;183;183 168;202;202;174;181;162;190;190 RT;RT 75;98 96;100 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The appearance of a lysine to glutamic acid change at position 43 (K43E) is strongly associated with NRTI-treatment. 2008 Retrovirology Introduction HIV K43E;K43E 67;20 71;65 NRTI 101 105 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The glutamic acid to phenylalanine change at codon 40 (E40F) is the result of as much as three transversions and is absent in the untreated population. 2008 Retrovirology Introduction HIV E40F;E40F 55;4 59;53 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The K43E does not decrease Zidovudine susceptibility but increases RC, when combined with E40F, acting as a compensatory mutation. 2008 Retrovirology Introduction HIV E40F;K43E 90;4 94;8 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. These mutations include the K20R, V35M, T39A, E40F, K43E/Q/N, A98G, K122E, G196E, E203K/D, H208Y, D218E, H221Y, K223E/Q and L228H/R changes. 2008 Retrovirology Introduction HIV A98G;D218E;E203D;E203K;E40F;G196E;H208Y;H221Y;K122E;K20R;K223E;K223Q;K43E;K43N;K43Q;L228H;L228R;T39A;V35M 62;98;82;82;46;75;91;105;68;28;112;112;52;52;52;124;124;40;34 66;103;89;89;50;80;96;110;73;32;119;119;60;60;60;131;131;44;38 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. This mutation has an even higher association with NRTI treatment when compared to specific known drug-resistance mutations such as M41L, K219E and K65R (Stanford HIV Drug Resistance database). 2008 Retrovirology Introduction HIV K219E;K65R;M41L 137;147;131 142;151;135 NRTI 50 54 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. We have demonstrated that the E40F change results in an increase in Zidovudine resistance and a decrease in RC. 2008 Retrovirology Introduction HIV E40F 30 34 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). Evidence that deletion of such genes provides a route for improvement of MVA immunogenicity is provided by reports of augmented protective mouse CD8+ T cell responses elicited by MVA lacking B15R, encoding an IL-1beta binding protein, and A41L, encoding a chemokine binding protein of unknown specificity. 2008 PloS one Introduction HIV A41L 239 243 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). Recombination-mediated genetic engineering (recombineering) of this construct permits more rapid generation of mutants for analysis than can be achieved by traditional methods, with the possible exception of host-range selection on rabbit cells using K1L . 2008 PloS one Introduction HIV K1L 251 254 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. A recent study on N348I provided evidence to link diminished RNase H cleavage and increased rates of excision. 2008 The Journal of biological chemistry Introduction HIV N348I 18 23 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Here we show that N348I and A360V compromise binding of transiently formed DNA RNA hybrids selectively in the context of RNase H-competent complexes. 2008 The Journal of biological chemistry Introduction HIV A360V;N348I 28;18 33;23 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. In addition, A371V and Q509L in the RNase H domain emerge under the selective pressure of AZT in cell culture. 2008 The Journal of biological chemistry Introduction HIV A371V;Q509L 13;23 18;28 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Most importantly, many of these mutations, including mutations N348I, A360I/V, and A371V, in the connection domain of HIV-1 RT were identified in clinical samples of HIV-infected individuals. 2008 The Journal of biological chemistry Introduction HIV A360I;A360V;A371V;N348I 70;70;83;63 77;77;88;68 RT 124 126 HIV infections 166 178 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. N348I was also shown to confer low level resistance to AZT and NNRTIs in the absence of TAMs. 2008 The Journal of biological chemistry Introduction HIV N348I 0 5 NNRTI 63 69 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The rare G333D/E polymorphisms have been associated with dual resistance to AZT and other NRTIs, and few connection mutations, including Y318F and N348I, have been linked to decreased susceptibility to NNRTIs. 2008 The Journal of biological chemistry Introduction HIV G333D;G333E;N348I;Y318F 9;9;147;137 16;16;152;142 NNRTI;NRTI 202;90 208;95 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. This region includes polymerase domain mutations M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E, which are referred to as thymidine analogue-associated mutations (TAMs). 2008 The Journal of biological chemistry Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 55;87;87;61;67;49;74;74 59;94;94;65;72;53;81;81 Pol 21 31 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. To address this problem, we have focused on the study of connection domain mutations A360V and N348I. 2008 The Journal of biological chemistry Introduction HIV A360V;N348I 85;95 90;100 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. G48V is one of the primary drug resistant mutations selected during treatment with saquinavir. 2008 Journal of molecular biology Introduction HIV G48V 0 4 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. I50V arises in treatment with amprenavir, and also confers resistance to darunavir. 2008 Journal of molecular biology Introduction HIV I50V 0 4 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. In this study, PR variants with the individual flap mutations G48V, I50V, I54V and I54M were analyzed to gain insight into their role in the development of drug resistance. 2008 Journal of molecular biology Introduction HIV G48V;I50V;I54M;I54V 62;68;83;74 66;72;87;78 PR 15 17 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Mutations I54M and I54L are frequent in clinical isolates resistant to darunavir. 2008 Journal of molecular biology Introduction HIV I54L;I54M 19;10 23;14 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Mutations of I54M and I54V are commonly observed during therapy with multiple PR inhibitors. 2008 Journal of molecular biology Introduction HIV I54M;I54V 13;22 17;26 PR 78 80 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Previously, the crystal structure of the double mutant G48V/L90M with saquinavir was analyzed, and we reported the structure of the PRI50V mutant with darunavir. 2008 Journal of molecular biology Introduction HIV G48V;L90M 55;60 59;64 PR 132 134 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Previously, we have analyzed the structures, activities, inhibition and stability of PR variants with the single substitutions of flap residues M46L, G48V, I50V, and F53L. 2008 Journal of molecular biology Introduction HIV F53L;G48V;I50V;M46L 166;150;156;144 170;154;160;148 PR 85 87 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In the present study, we took advantage of early post-entry defects reported for HIV-1 mutants bearing S109A, S149A and S178A substitutions in CA to investigate the functional role of the CA shell in early steps of replication. 2008 Retrovirology Introduction HIV S109A;S149A;S178A 103;110;120 108;115;125 Capsid;Capsid 143;188 145;190 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. S109A resulted in drastic alteration of core assembly and incomplete Gag precursor cleavage. 2008 Retrovirology Introduction HIV S109A 0 5 Gag 69 72 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Surprisingly, we found that when pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G), S149A and S178A, but not S109A, became competent for 2-LTR circle formation and established productive infection of the host cell. 2008 Retrovirology Introduction HIV S109A;S149A;S178A 128;103;113 133;108;118 LTR 158 161 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The most commonly identified enfuvirtide resistance mutations include G36D or S, V38A, M or E, Q40H and N43D. 2008 Journal of acquired immune deficiency syndromes (1999) Introduction HIV G36D;N43D;Q40H;V38A 70;104;95;81 74;108;99;85 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. The most common NVP resistance mutation detected in infants after SD NVP is Y181C, although other mutations are also seen. 2008 The Journal of infectious diseases Introduction HIV Y181C 76 81 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Additional mutations have been reported (L74M, E92Q, E138K, G140S/A and G163R). 2008 Biochemistry Introduction HIV E138K;E92Q;G140A;G140S;G163R;L74M 53;47;60;60;72;41 58;51;67;67;77;45 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. For elvitegravir, T66I and E92Q are the two mutations that contribute the most to resistance (37- and 36-fold reduced susceptibility to elvitegravir, respectively). 2008 Biochemistry Introduction HIV E92Q;T66I 27;18 31;22 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. For raltegravir the two main mutations are N155H or Q148H/R/K with 10- and 25-fold in vivo resistance, respectively. 2008 Biochemistry Introduction HIV N155H;Q148H;Q148K;Q148R 43;52;52;52 48;61;61;61 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Other mutations reported for elvitegravir are H51Y, T66I, Q95K, E138K, Q146P, S147G and E157Q. 2008 Biochemistry Introduction HIV E138K;E157Q;H51Y;Q146P;Q95K;S147G;T66I 64;88;46;71;58;78;52 69;93;50;76;62;83;56 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. An unusual second binding site for DRV was observed in the two high-resolution crystal structures of complexes with HIV-1 PR mutants with the single substitutions of V32I (0.84 A) and M46L (1.22 A). 2008 Journal of medicinal chemistry Introduction HIV M46L;V32I 184;166 188;170 PR 122 124 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. Here, we report on solution measurements of enzyme inhibition kinetics for an optimized wild-type HIV-1 PR denoted PRWT and the V32I mutant PR (PRV32I) with three PIs: DRV, amprenavir (APV), and saquinavir (SQV) (Figure 1c). 2008 Journal of medicinal chemistry Introduction HIV V32I 128 132 PI;PR;PR;PR 163;104;140;144 166;106;142;146 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. Introduction of the V32I mutation significantly reduces the PR activity for this substrate based on the p2-NC cleavage site of the viral polyprotein substrate (Table 1). 2008 Journal of medicinal chemistry Introduction HIV V32I 20 24 NC;PR 107;60 109;62 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. The difference in relative activity on the two substrates is likely due to differences in the peptide sequences, which suggests mutation V32I is deleterious for correct polyprotein processing and viral replication. 2008 Journal of medicinal chemistry Introduction HIV V32I 137 141 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. Therefore, the V32I mutation is likely to induce resistance to the three tested PIs. 2008 Journal of medicinal chemistry Introduction HIV V32I 15 19 PI 80 83 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. Because of the crucial structural and functional roles exhibited by the two conserved aspartyl residues Asp25 and Asp29 of HIV-1 protease, we have now systematically examined the effect of individual substitution mutations (D25N or D29N) on the binding of selected PIs (DRV, ATV, SQV, RTV, APV) based on DSC analyses and compared them to the binding of one tightbinding symmetric inhibitor (DMP323) and 2 substrate mimetics (RPB and Ac-PEP). 2009 Proteins Introduction HIV D25N;D29N 224;232 229;236 PR;Asp;Asp;PI 129;104;114;265 137;107;117;268 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. For example, the D25N mutation increases the ligand dissociation constant of PRD25N/DRV by a factor of ~106 relative to PR/DRV. 2009 Proteins Introduction HIV D25N;D25N 17;79 21;83 PR;PR 77;120 79;122 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. Subtle mutation of the Asp29 or Arg87 residue increases the dimer dissociation constant (Kd), R87K mutation exerting a dramatic effect (> 104) on Kd compared with a D29N (> 102) mutation. 2009 Proteins Introduction HIV D29N;R87K 165;94 169;98 Asp 23 26 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. By contrast, the mutations M41L, D67N, K70R, L210W, T215F/Y and K219Q/E - typically referred to as thymidine analog mutations (TAMs) - augment the ability of HIV-1 RT to excise the chain-terminating NRTI-monophosphate from a prematurely terminated DNA chain. 2008 AIDS (London, England) Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 33;64;64;39;45;27;52;52 37;71;71;43;50;31;59;59 NRTI;RT 199;164 203;166 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. The K65R, K70E, L74V, Q151M and M184V mutations primarily increase the selectivity of RT for the incorporation of a natural dNTP substrate over a NRTI-triphosphate. 2008 AIDS (London, England) Introduction HIV K65R;K70E;L74V;M184V;Q151M 4;10;16;32;22 8;14;20;37;27 NRTI;RT 146;86 150;88 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Additional studies revealed that the IN-induced lethal phenotype may be related to the catalytic activity of IN as an IN catalytic mutant (D116A) was unable to induce the lethal phenotype in yeast. 2008 Retrovirology Introduction HIV D116A 139 144 IN;IN;IN 37;109;118 39;111;120 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Furthermore, our data also indicated that this replication defect was partially complemented by the IN class I catalytic mutant D64E. 2008 Retrovirology Introduction HIV D64E 128 132 IN 100 102 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. By comparison, A371V in combination with the same TAMs did not augment AZT resistance, although high-level AZT resistance was observed with viruses containing D67N, K70R, T215F, A371V, and Q509L. 2008 Biochemistry Introduction HIV A371V;A371V;D67N;K70R;Q509L;T215F 15;178;159;165;189;171 20;183;163;169;194;176 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. demonstrated that the mutations H539N and D549N in the RNase domain significantly increase AZT resistance alone and in combination with thymidine analogue mutation (TAMs). 2008 Biochemistry Introduction HIV D549N;H539N 42;32 47;37 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. H539N and D549N, however, have not been reported to be selected by AZT. 2008 Biochemistry Introduction HIV D549N;H539N 10;0 15;5 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In the current study, we sought to address this issue by determining the mechanism(s) by which Q509L in HIV-1 RT increases AZT resistance when combined with D67N, K70R, and T215F. 2008 Biochemistry Introduction HIV D67N;K70R;Q509L;T215F 157;163;95;173 161;167;100;178 RT 110 112 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Site-directed mutagenesis studies demonstrated that Q509L increased AZT resistance 7.4-fold when combined with D67N, K70R, and T215F. 2008 Biochemistry Introduction HIV D67N;K70R;Q509L;T215F 111;117;52;127 115;121;57;132 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. This study identified two novel mutations in the connection domain (A371V) and RNase H domain (Q509L) of RT that were selected in combination with D67N, K70R, and T215F. 2008 Biochemistry Introduction HIV A371V;D67N;K70R;Q509L;T215F 68;147;153;95;163 73;151;157;100;168 RT 105 107 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Another cardiac-targeted TG expressed a mutant (Y955C) of the DNA polymerase-gamma (pol-gamma) uniquely responsible for mtDNA replication. 2009 Laboratory investigation; a journal of technical methods and pathology Introduction HIV Y955C 48 53 Pol;Pol 66;84 76;87 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Overexpression of native TK2, and two mutants of TK2 (H121N and I212N; known to cause 'inherited mtDNA depletion syndromes') were used. 2009 Laboratory investigation; a journal of technical methods and pathology Introduction HIV H121N;I212N 54;64 60;69 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Y955C is the commonest, most severe autosomal dominant POLG mutation. 2009 Laboratory investigation; a journal of technical methods and pathology Introduction HIV Y955C 0 5 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. Here, we show that the isolated HTH motif continues to fulfill three of the major functions of the whole parental enzyme: i) it recognizes the U5LTR extremity of viral DNA at the attachment-processing site in a specific manner i.e., it preserves its viral DNA binding property; ii) it self-associates and associates to IN i.e., it reproduces some of the enzyme oligomerisation behavior, and iii) it binds to the IBD of LEDGF but not to its Asp366Asn-IBD variant lacking the essential Asp366 residue i.e., it maintains its ability to interact with specific partners. 2009 PloS one Introduction HIV D366D;D366I;D366N 440;440;440 449;449;449 Asp;Asp;IN 440;484;319 443;487;321 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. It has been logically preferred to the native wt sequence (Table 1a) because it is the Phe185Lys variant that was used in the various crystallizations and co-crystallizations so far reported. 2009 PloS one Introduction HIV F185K 87 96 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. The peptide dealt with in this work represents the sequence found in the IN-CC Phe185Lys variant (Table 1a). 2009 PloS one Introduction HIV F185K 79 88 IN 73 75 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. The Phe185Lys mutation is not expected to affect the interactions with LTR and LEDGF IBD. 2009 PloS one Introduction HIV F185K 4 13 LTR 71 74 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. (ii) In most cases, the Q148H mutation occurs simultaneously with the G140S mutation. 2009 Nucleic acids research Introduction HIV G140S;Q148H 70;24 75;29 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Accordingly, the in vitro activity of the G140S/Q148H mutant can reach a wild-type level of activity while the single mutant Q148H cannot. 2009 Nucleic acids research Introduction HIV G140S;Q148H;Q148H 42;48;125 47;53;130 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Finally, we found that the G140S/Q148H mutant was much more resistant than the N155H mutant. 2009 Nucleic acids research Introduction HIV G140S;N155H;Q148H 27;79;33 32;84;38 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In particular, we investigated the effect of the G140S/Q148H double mutation, by constructing both the Q148H and G140S single mutants as well as the double mutant. 2009 Nucleic acids research Introduction HIV G140S;G140S;Q148H;Q148H 49;113;55;103 54;118;60;108 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Others mutations, such as the E92 and E157Q, have also been described. 2009 Nucleic acids research Introduction HIV E157Q 38 43 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Our kinetic study reveals that Q148H is a catalytic mutant blocked in an inactive conformation. 2009 Nucleic acids research Introduction HIV Q148H 31 36 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The G140S mutation did not confer strong resistance, but restored the replication capability of the Q148H mutant. 2009 Nucleic acids research Introduction HIV G140S;Q148H 4;100 9;105 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The G140S mutation induces a conformational transition compatible with activity. 2009 Nucleic acids research Introduction HIV G140S 4 9 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The Q148H mutation may be present as a single mutation at the beginning of the treatment, but the G140S mutation appears after a few weeks of treatment. 2009 Nucleic acids research Introduction HIV G140S;Q148H 98;4 103;9 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We found that the Q148H mutation caused resistance to RAL when present alone. 2009 Nucleic acids research Introduction HIV Q148H 18 23 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We investigated the impact of the two main genetic resistance pathways (N155H and G140S/Q148H), on viral replication and the catalytic properties of recombinant INs. 2009 Nucleic acids research Introduction HIV G140S;N155H;Q148H 82;72;88 87;78;93 IN 161 164 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Four mutations at the dimeric interface (W184A and M185A at the helix 2 region and Q155N and E159D at the MHR) were carefully selected to examine the effect of specific single point mutation on the association force, structural stability, and folding of CTDs of the CA protein (Table 1). 2009 Biomacromolecules Introduction HIV E159D;M185A;Q155N;W184A 93;51;83;41 98;56;88;47 Capsid 266 268 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Four mutations were used in the simulations: W184A and M185A located in helix 2 region, and Q155N and E159D located in major homology region (MHR). 2009 Biomacromolecules Introduction HIV E159D;M185A;Q155N;W184A 102;55;92;45 107;60;97;50 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. reported that conservative mutation of two invariant residues at the major homology region (MHR) of the CTDs (Q155N and E159D) significantly abolished viral replication. 2009 Biomacromolecules Introduction HIV E159D;Q155N 120;110 125;116 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. They found that only M39A and A42D at the NTDs and W184A at the CTDs severely attenuated the formation of cylindrical capsid, thus reducing virus infectivity. 2009 Biomacromolecules Introduction HIV A42D;M39A;W184A 30;21;51 34;25;56 Capsid 118 124 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. A possible alternative and third pathway, Y143R/C, also exists. 2009 Retrovirology Introduction HIV Y143C;Y143R 42;42 49;49 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. G140S was not documented by Rhee et al. 2009 Retrovirology Introduction HIV G140S 0 5 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. However, both G140S mutations in our study occurred in samples from previously ARV-treated individuals, suggesting that previous therapy may result in reduced INI efficacy, and further supporting IN sequencing in patients contemplating INI therapy initiation. 2009 Retrovirology Introduction HIV G140S 14 19 IN;IN;IN 159;236;196 162;239;198 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. However, in a small study conducted at Westmead Hospital, Sydney, Australia, G140S was detected in 2 INI-naive patients, as were the other accessory mutations: L74I/M (n = 8), T97A (n = 2), V151I (n = 3) and I203M (n = 4). 2009 Retrovirology Introduction HIV G140S;I203M;L74I;L74M;T97A;V151I 77;208;160;160;176;190 82;213;166;166;180;195 IN 101 104 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. In contrast, isolated L74A/I/M has no effect on in vitro resistance while G140S is associated with an in vitro 5-10 fold decrease in susceptibility (Personal communication with Merck Sharp & Dohme). 2009 Retrovirology Introduction HIV G140S;L74A;L74I;L74M 74;22;22;22 79;30;30;30 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. in their review of the Stanford HIV Database in only 3 isolates (each with a single primary INI mutation N155H, Q148H and Q148K). 2009 Retrovirology Introduction HIV N155H;Q148H;Q148K 105;112;122 110;117;127 IN 92 95 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. M154I, V165I and M185L) positively associated with specific RT mutations (F227L and T215Y) in samples from treated individuals. 2009 Retrovirology Introduction HIV F227L;M185L;T215Y;V165I;M154I 74;17;84;7;0 80;22;89;12;5 RT 60 62 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. Several IN polymorphisms (S24N, D25E, T112I, S119P, T125A, K136Q, V201I, L234I and S283G) were present in all three patients, suggesting that they were readily transmitted. 2009 Retrovirology Introduction HIV D25E;K136Q;L234I;S119P;S24N;S283G;T112I;T125A;V201I 32;59;73;45;26;83;38;52;66 36;64;78;50;30;88;43;57;71 IN 8 10 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. T97A, V151I, G163R, I203M and S230N) remains unknown. 2009 Retrovirology Introduction HIV G163R;I203M;S230N;V151I;T97A 13;20;30;6;0 18;25;35;11;4 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. These occur in one of two main pathways, either N155H or Q148H/K/R. 2009 Retrovirology Introduction HIV N155H;Q148H;Q148K;Q148R 48;57;57;57 53;66;66;66 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. This mutation is not only responsible for partial RAL resistance but also restores viral fitness when combined with the Q148R/H mutation. 2009 Retrovirology Introduction HIV Q148H;Q148R 120;120 127;127 19203393 HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. We are aware of possibly two additional isolates, one from an Australian isolate bearing N155H in an INI-naive patient. 2009 Retrovirology Introduction HIV N155H 89 94 IN 101 104 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Although subtype C viruses harbour a unique KKK nucleotide motif, amino acid polymorphisms and codon bias at position 65 cannot explain the differential acquisition of K65R in subtype C variants. 2009 Retrovirology Introduction HIV K65R 168 172 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In contrast, K65R is present in only 1.8% of subtype B HIV-1 infected patients failing d4T based regimens in the Stanford HIV Resistance Database (accessed Dec 11, 2008) and is only common in patients failing TFV-containing regimens (up to15%). 2009 Retrovirology Introduction HIV K65R 13 17 HIV infections 55 69 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In this work, we have characterized the enzymatic properties of recombinant B and wild-type RTs as well as RTs harboring the K65R and K65R/M184V mutations. 2009 Retrovirology Introduction HIV K65R;K65R;M184V 125;134;139 129;138;144 RT;RT 92;107 95;110 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Our laboratory has described the facilitated selection of K65R in subtype C in cell culture. 2009 Retrovirology Introduction HIV K65R 58 62 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Recent clinical studies show the preferential emergence of K65R in subtype C-infected patients failing d4T/ddI based regimens in Botswana (30%), and d4T/3TC-based regimens in South Africa and Malawi (7-20%). 2009 Retrovirology Introduction HIV K65R 59 63 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The present study was designed to determine if variations in enzymatic function might be responsible for the higher propensity of K65R to occur in subtype C. 2009 Retrovirology Introduction HIV K65R 130 134 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The RT mutation K65R can be selected by each of tenofovir (TFV), ddI, ddC, ABC and d4T and yields decreased susceptibility to all clinically used NRTIs except ZDV. 2009 Retrovirology Introduction HIV K65R 16 20 NRTI;RT 146;4 151;6 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. In apparent contradiction with this hypothesis, a mutant in which domain A had been inactivated by four mutations (m4-CVN, containing mutations Lys3Asn, Thr7Ala, Glu23Ile, Asn93Ala) inhibits HIV-1 envelope-mediated fusion with activity indistinguishable from wt CV-N. 2009 Biopolymers Introduction HIV E23I;K3N;N93A;T7A 162;144;172;153 170;151;180;160 Env 197 205 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. In this work, we introduced mutations to the hinge region designed to restore multivalency to the P51G-m4-CVN construct through the formation of an obligated domain-swapped dimer. 2009 Biopolymers Introduction HIV P51G 98 102 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Mutations that augment the flexibility of the hinge region, such as P51G, result in a stabilization of the monomer form. 2009 Biopolymers Introduction HIV P51G 68 72 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Mutations that introduce further constraints, such as S52P, DeltaQ50, and P51S-S52P, result in almost exclusive formation of the domain-swapped dimer. 2009 Biopolymers Introduction HIV P51S;S52P;S52P 74;54;79 78;58;83 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. P51G-m4-CVN bound gp120 with affinity almost three orders of magnitude weaker than CV-N. 2009 Biopolymers Introduction HIV P51G 0 4 gp120 18 23 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The constructs, S52P-m4-CVN and DeltaQ50-m4-CVN, contain two copies of domain B presented on the same side of the dimer (Figure 1B). 2009 Biopolymers Introduction HIV S52P 16 20 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The critical role of multivalency was supported by independent and complementary work on a monomeric domain B knockout mutant, CV-NmutDB, which contains several mutations that abolish binding in domain B as well as the P51G mutation that stabilizes the monomeric form. 2009 Biopolymers Introduction HIV P51G 219 223 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The domain-swapped dimer of P51G-m4-CVN can be obtained in 50% yields by partial unfolding in 2M guanidinium and slow refolding by dialysis at millimolar concentrations; once separated from the monomer by gel filtration, the dimer can be kept as metastable form at low temperatures. 2009 Biopolymers Introduction HIV P51G 28 32 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The high-resolution X-ray structures of the free and dimannose bound forms of P51G-m4-CVN confirmed the presence of a single-functional carbohydrate-binding domain (Figure 1A) and showed changes in the hinge region that explained the observed stabilization of the monomeric form. 2009 Biopolymers Introduction HIV P51G 78 82 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. To clarify these issues, we previously designed a mutant, P51G-m4-CVN, which like m4-CVN contains the four mutations that abolish binding in domain A, and an additional mutation in the hinge region, P51G, which stabilizes the monomeric form. 2009 Biopolymers Introduction HIV P51G;P51G 58;199 62;203 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. The high proportion of positively selected amino acids in this protein implies that the region contains multiple HLA epitopes as suggested by the significant correlations of K4R with B*1302 (P=0.0008) and S9N with A*7401 (P=0.0002). 2009 AIDS (London, England) Introduction HIV K4R;S9N 174;205 177;208 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Interestingly, some of these mutations appear to depend upon the presence of specific mutations in PR: Mutation A431V is mostly observed in PI-resistant viruses carrying mutations V82A and/or M46I in PR. 2009 PLoS pathogens Introduction HIV A431V;M46I;V82A 112;192;180 117;196;184 PI;PR;PR 140;99;200 142;101;202 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. It is, however, seen with significantly higher frequency in resistant viruses carrying the I84V mutation in PR and also specifically seen in resistant viruses carrying the I50V PR mutation, in association with L449F. 2009 PLoS pathogens Introduction HIV I50V;I84V;L449F 172;91;210 176;95;215 PR;PR 108;177 110;179 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Mutation L449F is frequently seen in viruses with mutation I84V in PR. 2009 PLoS pathogens Introduction HIV I84V;L449F 59;9 63;14 PR 67 69 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. recently reported the emergence of viruses carrying mutations K436E and I437V (Figure 1) within the SP2 linker peptide of Gag following in vitro selection for HIV-1 resistance to an experimental PI. 2009 PLoS pathogens Introduction HIV I437V;K436E 72;62 77;67 SP2;Gag;PI 100;122;195 103;125;197 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Selective reversion of mutations A431V or I437V in a subset of these recombinant viruses produced a strong reduction in resistance, but only a minor effect on replication capacity. 2009 PLoS pathogens Introduction HIV A431V;I437V 33;42 38;47 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Substitution P453L is a polymorphism found in some inhibitor-naive viruses. 2009 PLoS pathogens Introduction HIV P453L 13 18 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. The most frequently observed cleavage site mutations in this region are substitution A431V, located at position P2 of the NC-SP2 cleavage site, mutation L449F at position P1' of the SP2-P6 cleavage site, and mutations K436R and I437V, situated immediately downstream of the NC-SP2 site. 2009 PLoS pathogens Introduction HIV A431V;I437V;K436R;L449F 85;228;218;153 90;233;223;158 SP2;SP2;SP2;NC;NC;Gag 125;182;277;122;274;186 128;185;280;124;276;188 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. The most common mutations selected by single-dose nevirapine include K103N, Y181C, and G190A. 2009 The Journal of infectious diseases Introduction HIV G190A;K103N;Y181C 87;69;76 92;74;81 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. One potentially important trend observed in HIV-2-infected patients is the frequent emergence of mutations that encode the K65R and Q151M substitutions in reverse transcriptase (RT) (figure A1 in appendix A, which appears only in the electronic version of the Journal). 2009 The Journal of infectious diseases Introduction HIV K65R;Q151M 123;132 127;137 RT;RT 155;178 176;180 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. These changes are substantially more common in HIV-2 than in HIV-1 and often appear together with M184V in bulk sequences obtained from individuals who have received NRTI therapy. 2009 The Journal of infectious diseases Introduction HIV M184V 98 103 NRTI 166 170 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. 20 high-scoring library compounds failed to yield any actives, a viable core was identified that did lead to anti-HIV agents, which were potent against WT virus, but inactive towards the Y181C variant. 2009 Journal of chemical information and modeling Introduction HIV Y181C 187 192 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Consequently, as reported here, virtual screening has been performed to seek leads that show activity against both wild-type HIV as well as a variant that encodes the Y181C mutation. 2009 Journal of chemical information and modeling Introduction HIV Y181C 167 172 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. In addition, to enhance the possibility of finding robust leads that could adapt to alternative RT structures, a conventional RT structure and one for a Y181C mutant were included in the virtual screening. 2009 Journal of chemical information and modeling Introduction HIV Y181C 153 158 RT;RT 96;126 98;128 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. In particular, though some of the NNRTIs are effective against the troublesome Lys103Asn (K103N) variant, the Tyr181Cys (Y181C) mutation has been consistently problematic. 2009 Journal of chemical information and modeling Introduction HIV K103N;K103N;Y181C;Y181C 79;90;110;121 88;95;119;126 NNRTI 34 40 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. It was originally thought that the Y181-down orientation was associated with weak inhibitors; however, our interest in this binding mode was reignited in 2005 by the report of the 2be2 structure and its ligand, R221239, which is a very potent NNRTI against both WT HIV (IC50 = 2 nM) and a Tyr181Cys variant (IC50 = 5 nM). 2009 Journal of chemical information and modeling Introduction HIV Y181C 289 298 NNRTI 243 248 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. More than two million compounds were screened in the docking calculations using three crystal structures of RT, a conventional WT structure, one with an alternative conformation for Y181, and a structure of Y181C RT. 2009 Journal of chemical information and modeling Introduction HIV Y181C 207 212 RT;RT 108;213 110;215 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. So, the idea was that other ligands that are well-accommodated in the 2be2 structure and that avoid contact with Tyr181 might also be effective towards Y181C variants. 2009 Journal of chemical information and modeling Introduction HIV Y181C 152 157 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. The conventional 1rt4 structure, which was used in a prior docking exercise, and the high-resolution (2.5-A) 1jla structure containing the Y181C mutation were chosen. 2009 Journal of chemical information and modeling Introduction HIV Y181C 139 144 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Though only nine compounds were ultimately purchased and assayed, one compound shows low-micromolar activity against both viral strains, while two others show similar activity against either the WT or Y181C strain. 2009 Journal of chemical information and modeling Introduction HIV Y181C 201 206 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Early virological failure on a nucleoside reverse transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen is associated with emergence of the M184V mutation and an NNRTI resistance mutation in approximately 50-75% of patients in resource-rich settings. 2009 AIDS (London, England) Introduction HIV M184V 183 188 NNRTI;NRTI;NNRTI;NNRTI;NRTI 85;31;132;205;75 120;63;137;210;79 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. also recently reported that the A360V and A371V mutations are frequently observed in AZT-treated patients. 2009 Antiviral research Introduction HIV A360V;A371V 32;42 37;47 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. For example, the polymorphism G333D/E does not confer drug resistance by itself, but has been reported to contribute significantly to dual AZT-lamivudine (3TC) resistance when combined with EEMs and M184V. 2009 Antiviral research Introduction HIV G333D;G333E;M184V 30;30;199 37;37;204 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. In contrast, one of the connection subdomain mutations, N348I, is associated with resistance to both nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) and appears to be induced by regimens containing AZT, didanosine (ddI) and/or nevirapine (NVP). 2009 Antiviral research Introduction HIV N348I 56 61 NNRTI;NRTI;RT;RT 168;127;112;153 174;132;114;155 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Recently, it has been shown that the N348I mutation decreases the efficiency of RNase H cleavage and increases excision of AZT from AZT-terminated primer/templates, in the presence of the pyrophosphate donor ATP. 2009 Antiviral research Introduction HIV N348I 37 42 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Similarly, A371V and Q509L, which were selected in the background of D67N and K70R by high concentrations of AZT in vitro, show strong resistance to AZT and weak cross-resistance to 3TC, abacavir (ABC) and tenofovir (TNF/PMPA) in the presence of EEMs. 2009 Antiviral research Introduction HIV A371V;D67N;K70R;Q509L 11;69;78;21 16;73;82;26 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. The excision mechanism is associated with mutations at the polymerase domain, including M41L, D67N, K70R, L210W, T215F/Y and K219E/Q (excision-containing mutations, EEMs, also known as thymidine analogue-associated mutations [TAMs]). 2009 Antiviral research Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 94;125;125;100;106;88;113;113 98;132;132;104;111;92;120;120 Pol 59 69 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. This is now changing, as more attention is being focused on such substitutions, following recent publications from us and others showing that at least one connection subdomain mutation, N348I, contributes to multi-class drug resistance. 2009 Antiviral research Introduction HIV N348I 186 191 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. With the exception of N348I, the clinical relevance of these mutations remains to be clarified. 2009 Antiviral research Introduction HIV N348I 22 27 19436623 Role of atazanavir in the treatment of HIV infection. Accordingly, the risk for developing severe hyperbilirubinemia was as high as 24% in subjects with MDR1 wild-type alleles but as low as 0% in those homozygous for the 3435C > T polymorphism. 2009 Therapeutics and clinical risk management Introduction HIV C3435T 167 176 19436623 Role of atazanavir in the treatment of HIV infection. By contrast, mutation L76V, selected under virologic failure with other PIs, produces hypersusceptibility to ATV. 2009 Therapeutics and clinical risk management Introduction HIV L76V 22 26 PI 72 75 19436623 Role of atazanavir in the treatment of HIV infection. In patients taking ATV 400 mg qd, the 3435C > T polymorphism has been associated with lower ATV plasma levels and lower serum bilirubin levels. 2009 Therapeutics and clinical risk management Introduction HIV C3435T 38 47 19436623 Role of atazanavir in the treatment of HIV infection. In PI-naive patients, the most frequent mutation at failure under ATV is I50L, while in PI-experienced patients mutations I84V and N88S are more commonly selected. 2009 Therapeutics and clinical risk management Introduction HIV I50L;I84V;N88S 73;122;131 77;126;135 PI;PI 3;88 5;90 19436623 Role of atazanavir in the treatment of HIV infection. In this situation, the resistance barrier may be confined to a single key mutation (eg, I50L). 2009 Therapeutics and clinical risk management Introduction HIV I50L 88 92 19436623 Role of atazanavir in the treatment of HIV infection. Lankisch et al examined the effects of different polymorphisms in UGT1A1 (UGT1A1*28), UGT1A3 (-66) and UGT1A7 (-57T > G, W208R, N129K and R131K) genes on the risk of hyperbilirubinemia in patients treated with ATV. 2009 Therapeutics and clinical risk management Introduction HIV N129K;R131K;W208R 128;138;121 133;143;126 19436623 Role of atazanavir in the treatment of HIV infection. Mutations more significant to be included in the GIQ model are the following: L10F/I/V, K20M/R, L24I, D30N, V32I, L33F, M36I/L, I47V/A, G48V, I50V, I50L, F53L, I54V/L/A/M/T/S, L63P, A71V/T, G73S, V77I, V82A/F/T, I84V, N88D/S and L90M. 2009 Therapeutics and clinical risk management Introduction HIV A71T;A71V;D30N;F53L;G48V;G73S;I47A;I47V;I50L;I50V;I54A;I54L;I54M;I54S;I54T;I54V;I84V;K20M;K20R;L10F;L10I;L10V;L24I;L33F;L63P;L90M;M36I;M36L;N88D;N88S;V32I;V77I;V82A;V82F;V82T 182;182;102;154;136;190;128;128;148;142;160;160;160;160;160;160;212;88;88;78;78;78;96;114;176;229;120;120;218;218;108;196;202;202;202 188;188;106;158;140;194;134;134;152;146;174;174;174;174;174;174;216;94;94;86;86;86;100;118;180;233;126;126;224;224;112;200;210;210;210 19436623 Role of atazanavir in the treatment of HIV infection. Of note, I50L is only selected under ATV pressure and it causes higher susceptibility to other PIs such as amprenavir, darunavir, indinavir, lopinavir (LPV), nelfinavir (NFV) and saquinavir (SQV). 2009 Therapeutics and clinical risk management Introduction HIV I50L 9 13 PI 95 98 19436623 Role of atazanavir in the treatment of HIV infection. The 2677G > T polymorphism has recently been suggested as the possible candidate. 2009 Therapeutics and clinical risk management Introduction HIV G2677T 4 13 19436623 Role of atazanavir in the treatment of HIV infection. The C3435T polymorphism is a silent change and thus it is unlikely that it directly influences the expression of the MDR1 gene. 2009 Therapeutics and clinical risk management Introduction HIV C3435T 4 10 19436623 Role of atazanavir in the treatment of HIV infection. The prevalence of I50L in large HIV drug resistance mutation databases is generally very low. 2009 Therapeutics and clinical risk management Introduction HIV I50L 18 22 19436623 Role of atazanavir in the treatment of HIV infection. This list include changes at positions 10, 16, 20, 24, 32, 33, 34, 36, 46, 48, 50, 53, 54, 60, 62, 64, 71, 73, 82, 84, 85, 88, 90 and 93, although the only changes considered as major mutations are I50L, I84V and N88S. 2009 Therapeutics and clinical risk management Introduction HIV I50L;I84V;N88S 198;204;213 202;208;217 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Resistance to nevirapine (NVP) is of particular concern because single nucleotide polymorphisms that cause amino acid changes, such as K103N and Y181C, are associated with high levels of resistance. 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K103N;Y181C 135;145 140;150 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Detailed analysis using previously described mutations within the C-terminus identified a single point mutation, R90K, which can prevent the IL-12 blockade. 2009 PloS one Introduction HIV R90K 113 117 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Among the 108 non-B samples analyzed previously, 82 (75.9%) had N42S (vs. 2009 AIDS research and human retroviruses Introduction HIV N42S 64 68 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. ENF susceptibility results were obtained for five of six samples with ENF resistance mutations in HR1 and for 21/26 additional samples with N42S. 2009 AIDS research and human retroviruses Introduction HIV N42S 140 144 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Five samples with E137K and one sample with S138A also had N42S; one sample with E137K also had N42S and L44M. 2009 AIDS research and human retroviruses Introduction HIV E137K;E137K;L44M;N42S;N42S;S138A 18;81;105;59;96;44 23;86;109;63;100;49 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. HIV from another sample that had N42S + L44M without E137K (#0171) had a fold change IC50 of 1.3 (susceptible. 2009 AIDS research and human retroviruses Introduction HIV E137K;L44M;N42S 53;40;33 58;44;37 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. L44M was detected in three men who had no evidence of resistance to other antiretroviral drugs. 2009 AIDS research and human retroviruses Introduction HIV L44M 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. none in EXPLORE), seven (6.5%) had E137K (vs. 2009 AIDS research and human retroviruses Introduction HIV E137K 35 40 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. One man had two ENF resistance mutations: L43K and L45M; that man also had resistance to all three NNRTIs (nevirapine, delavirdine, and efavirenz). 2009 AIDS research and human retroviruses Introduction HIV L43K;L45M 42;51 46;55 NNRTI 99 105 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Polymorphisms in the HR2 region (e.g., N126K, E137K, and S138A) may increase the fitness of HIV-1 viruses that have ENF resistance mutations in HR1. 2009 AIDS research and human retroviruses Introduction HIV E137K;N126K;S138A 46;39;57 51;44;62 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. The HIV from that sample (#0168) had the HR1 ENF resistance mutations N42S + L44M, as well as the HR2 accessory mutation E137K, and had a fold change IC50 of 24. 2009 AIDS research and human retroviruses Introduction HIV E137K;L44M;N42S 121;77;70 126;81;74 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. The HR2 accessory mutations, E137K and S138A, were detected in 27 (15.4%) and 15 (8.6%) of the 175 EXPLORE samples, respectively; four samples had both E137K and S138A. 2009 AIDS research and human retroviruses Introduction HIV E137K;E137K;S138A;S138A 29;152;39;162 34;157;44;167 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. The mutations analyzed included (1) mutations in HR1 that are associated with a >10-fold reduction in most clinical isolates and site-directed mutants (major mutations: G36D/E, V38A/E, Q40H, and N43D), (2) other ENF resistance mutations in HR1 (G36S/V, I37V, V38G/M, N42T, N43K, L44M, and L45M), (3) N42S, a natural polymorphism in HR1 that has been associated with ENF hypersusceptibility, and (4) HR2 accessory mutations (N126K, E137K, and S138A). 2009 AIDS research and human retroviruses Introduction HIV E137K;G36D;G36E;G36S;G36V;I37V;L44M;L45M;N126K;N42T;N43D;N43K;Q40H;S138A;V38A;V38E;V38G;V38M 431;169;169;245;245;253;279;289;424;267;195;273;185;442;177;177;259;259 436;175;175;251;251;257;283;293;429;271;199;277;189;447;183;183;265;265 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. The N42S polymorphism was detected in 28 (16%) of the 175 samples, including two samples that also had L44M, one of which also had E137K (see below). 2009 AIDS research and human retroviruses Introduction HIV E137K;L44M;N42S 131;103;4 136;107;8 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Two of the six samples that had minor ENF resistance mutations also had genotypic evidence of resistance to other antiretroviral drugs: one sample with V38G also had genotypic evidence of resistance to three other classes of antiretroviral drugs (NRTIs, NNRTIs, and PIs), and one sample with N43K and L45M also had genotypic evidence of NNRTI resistance. 2009 AIDS research and human retroviruses Introduction HIV L45M;N43K;V38G 301;292;152 305;296;156 NNRTI;NNRTI;NRTI;PI 254;337;247;266 260;342;252;269 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Using the Stanford HIV Resistance Database as a reference, we identified minor HR1 mutations associated with reduced susceptibility to ENF in 6 (3.4%) of 175 samples from men in the EXPLORE cohort (V38G, N43K, L44M, and L45M). 2009 AIDS research and human retroviruses Introduction HIV L44M;L45M;N43K;V38G 210;220;204;198 214;224;208;202 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. V38G was detected in samples from two men, one of whom also had resistance to nucleoside reverse transcriptase inhibitors (NRTIs; zidovudine and stavudine, with possible resistance to didanosine and tenofovir), nonnucleoside reverse transcriptase inhibitors (NNRTIs; nevirapine, delavirdine, and efavirenz), and protease inhibitors (PIs; indinavir, saquinavir, ritonavir, and nelfinavir, with possible resistance to amprenavir, fosamprenavir, lopinavir, and atazanavir). 2009 AIDS research and human retroviruses Introduction HIV V38G 0 4 NNRTI;NRTI;PR;NNRTI;NRTI;PI 211;78;312;259;123;333 246;110;320;265;128;336 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. We also detected the N42S hypersusceptibility mutation in 28 (16%) of the 175 samples; this is similar to the rate of detection of N42S in other cohorts of ENF-naive individuals with subtype B HIV infection. 2009 AIDS research and human retroviruses Introduction HIV N42S;N42S 21;131 25;135 HIV infections 193 206 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. We detected E137K in 27 (15.4%) of the samples and detected S138A in 15 (8.6%) of the samples; four samples had both of these polymorphisms. 2009 AIDS research and human retroviruses Introduction HIV E137K;S138A 12;60 17;65 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Eight infants had mutations detected by ViroSeq [Y181C (n = 4), K103N (n = 1), V106M (n = 1), Y188C (n = 1), and V179D+K103R (n = 1)], and four infants had resistance detected by LigAmp only (all with Y181C, at 1.2%, 1.4%, 3.5%, and 7.8%; one infant also had G190A at 1.9%). 2009 AIDS research and human retroviruses Introduction HIV G190A;K103N;K103R;V106M;V179D;Y181C;Y181C;Y188C 259;64;119;79;113;49;201;94 264;69;124;84;118;54;206;99 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. For samples with subtype A or D HIV, PCR products produced in the ViroSeq system were also tested using the LigAmp assay (assay cutoffs for mutation detection: 0.5% for K103N, 1.0% for Y181C, 0.5% for G190A). 2009 AIDS research and human retroviruses Introduction HIV G190A;K103N;Y181C 201;169;185 206;174;190 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. In contrast, LigAmp detected K103N and G190A in a higher proportion of infants than ViroSeq (K103N: 23.6% vs. 2009 AIDS research and human retroviruses Introduction HIV G190A;K103N;K103N 39;29;93 44;34;98 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Most of the infants who had resistance detected at 6 or 12 months had Y181C. 2009 AIDS research and human retroviruses Introduction HIV Y181C 70 75 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. The median levels of the mutations (% of the viral population) were Y181C: 19.8% (range: 1.4-90.6%), K103N: 3.5% (range: 0.5-100%), and G190A: 2.2% (range: 0.7-19.6%). 2009 AIDS research and human retroviruses Introduction HIV G190A;K103N;Y181C 136;101;68 141;106;73 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. The proportion of infants who had K103N, Y181C, or G190A detected by LigAmp (33/72 = 45.8%) was similar to the proportion of infants who had resistance detected by ViroSeq (36/80 = 45.0%, p = 0.563). 2009 AIDS research and human retroviruses Introduction HIV G190A;K103N;Y181C 51;34;41 56;39;46 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. The two assays detected Y181C in a similar proportion of infants (LigAmp: 40.3%, ViroSeq: 35.0%, p = 0.157). 2009 AIDS research and human retroviruses Introduction HIV Y181C 24 29 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Thirty-six (45.0%) of the 80 infants had at least one NVP resistance mutation detected; the mutations identified were Y181C (n = 28), K103N (n = 9), Y188C (n = 3), G190A (n = 30), V106A (n = 2), V106M (n = 2), and K101E (n = 1); 10 infants had two or more NVP resistance mutations detected. 2009 AIDS research and human retroviruses Introduction HIV G190A;K101E;K103N;V106A;V106M;Y181C;Y188C 164;214;134;180;195;118;149 169;219;139;185;200;123;154 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. This is surprising, since Y181C fades from detection rapidly in Ugandan women after sdNVP, particularly among those with subtype A infection. 2009 AIDS research and human retroviruses Introduction HIV Y181C 26 31 HIV infections 121 140 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Two (25%) infants had resistance detected by both ViroSeq and LigAmp (one with G190A and one with Y181C) and two infants had resistance mutations detected by LigAmp only (both with Y181C, at 1.7% and 4.7%). 2009 AIDS research and human retroviruses Introduction HIV G190A;Y181C;Y181C 79;98;181 84;103;186 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Also, no apparent reversion to wild type at mutated codon M184V has been detected during virus propagation in the absence of drug. 2009 Antiviral research Introduction HIV M184V 58 63 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Although each are clinically important, K65R and L74V rarely occur on the same virus genome (Winters et al., 1997), and Stanford HIV drug resistance database (web site: http://hivdb.stanford.edu) confirm this rarity. 2009 Antiviral research Introduction HIV K65R;L74V 40;49 44;53 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Among 23 patients who received 1-2 years of 2',3'-dideoxyinosine (ddI) therapy, only one showed the presence of K65R and L74V on the same genome. 2009 Antiviral research Introduction HIV K65R;L74V 112;121 116;125 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Analysis of clinical data on the risks and incidence of K65R and L74V mutations on virologic responses have revealed that if suboptimal HAART is used, infected persons with K65R experienced significantly higher rates of virologic suppression than did those with L74V mutation. 2009 Antiviral research Introduction HIV K65R;K65R;L74V;L74V 56;173;65;262 60;177;69;266 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Analysis of the Marseille database containing 8,866 sequences from 3,720 patients revealed the coexistence of K65R and L74V in only two clones. 2009 Antiviral research Introduction HIV K65R;L74V 110;119 114;123 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Appropriate assays for direct comparison of the replication kinetics and RT processivity of the viruses with K65R and L74V will be needed to understand the overall impact of multidrug resistance mutations in viral suppression. 2009 Antiviral research Introduction HIV K65R;L74V 109;118 113;122 RT 73 75 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Based upon these observations, theoretically, it could be predicted that RT containing double mutation 65R and 74V would be significantly less processive than M184V RT. 2009 Antiviral research Introduction HIV M184V 159 164 RT;RT 73;165 75;167 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Could it be that an assay of 'C incorporation rather than "T" would better explain the clinical phenotype? It should be noted however, that in contrast to a decrease in processivity for M184V and K65R+L74V virion-associated RTs observed by us, no change in the processivity of 65R+74V RT was observed by. 2009 Antiviral research Introduction HIV K65R;L74V;M184V 196;201;186 200;205;191 RT;RT 224;285 227;287 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. For example passaging of HIVIAI in the presence of nucleoside reverse transcriptase inhibitors (NRTI), P-D-dioxolane guanine (DXG) or DAPD (Amdoxovir ), results in the selection of K65R or L74V, but both mutations were not selected together. 2009 Antiviral research Introduction HIV K65R;L74V 181;189 185;193 NRTI;NRTI 51;96 83;100 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. In a recent study, investigators demonstrated that under low dNTP concentration K65R RT exhibits lower activity in single-cycle processivity assay which is in agreement with our observation of a decreased processivity of K65R compared to WTRT. 2009 Antiviral research Introduction HIV K65R;K65R 80;221 84;225 RT 85 87 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. In contrast 3TC-selected M184V mutation is prevalent during clinical trials with combination therapy where 3TC or FTC is one of the component of regimen. 2009 Antiviral research Introduction HIV M184V 25 30 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. In recent years, several investigators have addressed the issue of clinical benefits in relation to nucleoside analog mutations K65R, L74V and M184V. 2009 Antiviral research Introduction HIV K65R;L74V;M184V 128;134;143 132;138;148 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. In this study, in vitro RT processivity of "T" nucleotides was used to compare "fitness" of the 65R+74V double mutant relative to WT, M184V and K65R, L74V, single mutants. 2009 Antiviral research Introduction HIV K65R;L74V;M184V 144;150;134 148;154;139 RT 24 26 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. It is widely believed that such synergistic drug interaction arises from the fact that certain combinations of drug resistance mutations are particularly detrimental for the enzyme, which leads to a less fit virus as shown by our group and others for RT variants containing mutations K65R, L74V and M184V ( and). 2009 Antiviral research Introduction HIV K65R;L74V;M184V 284;290;299 288;294;304 RT 251 253 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. On the other hand K65R RT has largest fidelity increase reported so far for RT mutants. 2009 Antiviral research Introduction HIV K65R 18 22 RT;RT 23;76 25;78 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Repositioning of finger region, beta4-beta3, in response to the changing L74V caused shifting of R72 and K65. 2009 Antiviral research Introduction HIV L74V 73 77 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. RT mutation M184V appears to be quite stable under therapy, however, upon discontinuation of lamivudine (3TC), 100% reversion to WT phenotype occurs after several months. 2009 Antiviral research Introduction HIV M184V 12 17 RT 0 2 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Since a major component of HAART, such as tenofovir disoproxil fumarate (TDF) can select for the RT mutation K65R while several nucleoside analogs (ddI, ddC, ABC) select for L74V (St.), our observations that the 65R and 74V mutations are mutually exclusive and results in an RT with severely reduced enzyme activity, may be clinically relevant. 2009 Antiviral research Introduction HIV K65R;L74V 109;174 113;178 RT;RT 97;275 99;277 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Since our assay showed similar decrease in M184V RT as observed previously by, a direct comparison of 65R+74V and other mutant RTs was performed. 2009 Antiviral research Introduction HIV M184V 43 48 RT;RT 49;127 51;130 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Since the combination of mutations in the background of K65R may have a more positive impact on viral suppression than those with L74V, it will be difficult to rule out the role of other mutation(s) involved with viral suppression in this scenario. 2009 Antiviral research Introduction HIV K65R;L74V 56;130 60;134 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Studies have clearly indicated that the presence of M184V during clinical trials lead to the maintenance of viral suppression and improved immunological profile even in the presence of 3TC or FTC. 2009 Antiviral research Introduction HIV M184V 52 57 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. The decreased processivity observed for L74V and M184V RTs were similar to those seen previously. 2009 Antiviral research Introduction HIV L74V;M184V 40;49 44;54 RT 55 58 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. The major goal of our study was to compare in vitro processivity of RTs containing a stable mutation M184V and an unstable double mutant 65R+74V. 2009 Antiviral research Introduction HIV M184V 101 106 RT 68 71 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. The role of M184V in viral suppression and overall clinical benefits has been studied by various investigators. 2009 Antiviral research Introduction HIV M184V 12 17 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. This work, as well as previous crystallographic and modeling studies, suggests M184V most likely causes resistance to specific drugs due to increased steric hindrance by beta-branched amino acids and can also cause repositioning of template-primer. 2009 Antiviral research Introduction HIV M184V 79 84 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Through this extended secondary structure mechanism the volume change associated with L74V is expected to alter absolute positioning of residue 65 as well as template positioning. 2009 Antiviral research Introduction HIV L74V 86 90 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. To eliminate the possibility of reversion during reverse transcription in mutant K65R+L74V virus, we used primary human embryonic kidney cells (293), R which are non-permissive for HIV-1 infection. 2009 Antiviral research Introduction HIV K65R;L74V 81;86 85;90 RT 49 70 HIV infections 181 196 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Under the assay conditions, the maximum lengths for cDNA synthesized by WT, 65R, 74V, 65R+74V and M184V RTs were 66, 60, 62, 42 and 37 nucleotides respectively. 2009 Antiviral research Introduction HIV M184V 98 103 RT 104 107 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. Unfortunately, the homopolymer processivity assays may not be enough to distinguish stability of mutant M184V observed during clinical trials with the rare mutant 65R+74V. 2009 Antiviral research Introduction HIV M184V 104 109 19555722 Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V. While M184V RT is associated with increased fidelity, L74V RT does not show significant increase in fidelity. 2009 Antiviral research Introduction HIV L74V;M184V 54;6 58;11 RT;RT 12;59 14;61 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. As seen in figure 4, V38E and V38A along with G36D replicated faster and to higher levels than WT. 2009 AIDS research and human retroviruses Introduction HIV G36D;V38A;V38E 46;30;21 50;34;25 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. Env glycoprotein that is defective in cell to cell fusion but capable of virus infection (W596M) has been shown to replicates faster than WT virus. 2009 AIDS research and human retroviruses Introduction HIV W596M 90 95 Env 0 3 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. Furthermore the replication kinetics of V38M was also similar to WT. 2009 AIDS research and human retroviruses Introduction HIV V38M 40 44 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. Furthermore, the Enfuvirtide resistant virus G36D (G547D based on Env numbering) was shown to be reduced in its bystander apoptosis inducing potential. 2009 AIDS research and human retroviruses Introduction HIV G36D;G547D 45;51 49;57 Env 66 69 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. However, in another study by Descamps et al G36D was associated with increased CD4 counts although not statistically significant. 2009 AIDS research and human retroviruses Introduction HIV G36D 44 48 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. In our assay V38E was found to be most resistant to Enfuvirtide and the least pathogenic raising the possibility that perhaps new generation of gp41 inhibitors may be able to select even more divergent and attenuated viruses. 2009 AIDS research and human retroviruses Introduction HIV V38E 13 17 gp41 144 148 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. In the case of Enfuvirtide resistant viruses also, we saw that while cell to cell fusion was severely affected especially for mutant V38E, the virus was still capable of infection. 2009 AIDS research and human retroviruses Introduction HIV V38E 133 137 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. It is thus not surprising that the mutant with the most resistance to Enfuvirtide (V38E) was the poorest inducer of cell to cell fusion and apoptosis. 2009 AIDS research and human retroviruses Introduction HIV V38E 83 87 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. On the other hand, the replication kinetics of V38M seemed to be strikingly similar to WT consistent with its apoptosis inducing capacity and decreased CD4 counts in vivo. 2009 AIDS research and human retroviruses Introduction HIV V38M 47 51 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. Recently it has been reported that V38E mutation is selected in vitro in response to the second generation fusion inhibitor T1249 exposure. 2009 AIDS research and human retroviruses Introduction HIV V38E 35 39 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. The degree of resistance was in the order WTV38M>V38A>G36D>V38E. 2009 AIDS research and human retroviruses Introduction HIV G36D;V38A;V38E;V38M 50;45;55;40 54;49;59;44 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. The other mutants V38A and G36D were found to be intermediate inducers of apoptosis in our experiments. 2009 AIDS research and human retroviruses Introduction HIV G36D;V38A 27;18 31;22 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. These results further support the argument that V38A/E and G36D mutants may be less pathogenic in vivo. 2009 AIDS research and human retroviruses Introduction HIV G36D;V38A;V38E 59;48;48 63;54;54 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. This is an interesting observation as V38M has been shown to be associated negatively with CD4 counts in patients. 2009 AIDS research and human retroviruses Introduction HIV V38M 38 42 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. V38E was found to be the most resistant with an IC50 of 2097.84 +- 60.54 nM while V38M was the least resistance with an IC50 of 46.69 +- 29.90 nM (Table 1). 2009 AIDS research and human retroviruses Introduction HIV V38M;V38E 82;0 86;4 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. We find that one such mutant V38E was the poorest inducer of apoptosis, while V38M was capable of apoptosis induction almost 60% of WT. 2009 AIDS research and human retroviruses Introduction HIV V38E;V38M 29;78 33;82 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. While V38A/E have been associated with increased CD4 counts in a study by Aquaro et al, the increase in counts associated with G36D was not statistically significant. 2009 AIDS research and human retroviruses Introduction HIV G36D;V38A;V38E 127;6;6 131;12;12 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. More recently the K65R mutation has also been reported in non-subtype B patients receiving non-TDF-containing first-line antiretroviral regimens This finding has significant implications for second and third line ART regimen choices in resource-limited settings, where TDF is often reserved for use due to its relatively high cost and resultant sustainability considerations. 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K65R 18 22 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Responses to these TDF-containing second or third line regimens among patients in whom K65R developed while on first line therapy may thus be significantly impacted. 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K65R 87 91 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The K65R mutation is selected by tenofovir, didanosine, abacavir and possibly stavudine usage, and causes a variable loss of susceptibility to tenofovir (TDF), didanosine and abacavir depending on the presence of thymidine analogue mutations (TAM). 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K65R 4 8 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. We describe preliminary results from these genotype analyses and provide a more detailed description of mutational and clinical characteristics in a smaller cohort of patients in which the K65R mutation was observed. 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K65R 189 193 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. K103N reduces susceptibility to efavirenz and nevirapine by ~20-fold and ~50-fold, respectively, but has no effect on susceptibility to the most recently approved NNRTI, etravirine. 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K103N 0 5 NNRTI 163 168 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The RT mutation K103N is the most commonly occurring NNRTI-resistance mutation in patients with acquired and transmitted NNRTI resistance. 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K103N 16 21 NNRTI;NNRTI;RT 53;121;4 58;126;6 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. To determine whether minority etravirine-resistance variants are present in patient samples, we performed ultra-deep pyrosequencing (UDPS; 454 Life Sciences, a Roche Company, FLX technology) of plasma samples from treatment-naive and NNRTI-experienced patients for whom direct PCR sequencing detected K103N but no other major NNRTI-resistance mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K103N 301 306 NNRTI;NNRTI 234;326 239;331 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. Efavirenz plasma exposure is increased in patients with the homozygous G516T genotype of CYP2B6. 2009 The Journal of antimicrobial chemotherapy Introduction HIV G516T 71 76 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. Studies on the differences between subtypes B and C relating to genetic variations at NNRTI resistance-associated positions have shown that mutation at positions such as V106M and A98S is more common for patients with subtype C than B. 2009 The Journal of antimicrobial chemotherapy Introduction HIV A98S;V106M 180;170 184;175 NNRTI 86 91 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. The C1459T polymorphism has been reported not to affect efavirenz exposure. 2009 The Journal of antimicrobial chemotherapy Introduction HIV C1459T 4 10 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. The G516T genotype is more common in African Americans than in European Americans and this has been reported to cause greater efavirenz exposure, although there is considerable overlap between racial/ethnic populations. 2009 The Journal of antimicrobial chemotherapy Introduction HIV G516T 4 9 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. 2) and evaluation of their activity against wild-type RT and K103N and Y181C mutant RT enzymes. 2009 Beilstein journal of organic chemistry Introduction HIV K103N;Y181C 61;71 66;76 RT;RT 54;84 56;86 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. On the basis of molecular modeling analysis on the wild-type (WT) and Y181C HIV-1 RT, it was found that the dipyridodiazepinone derivatives containing an unsubstituted lactam nitrogen and a 2-chloro-8-arylthiomethyl moiety, when compared with 9. 2009 Beilstein journal of organic chemistry Introduction HIV Y181C 70 75 RT 82 84 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Among the most frequent in treatment-experienced populations are M184V and TAMs, and less frequent but positively associated are M184V with K65R; in contrast, K65R and TAMs or K65R and L74V are rarely present together. 2009 The Journal of biological chemistry Introduction HIV K65R;K65R;K65R;L74V;M184V;M184V 140;159;176;185;65;129 144;163;180;189;70;134 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Here we report the crystal structures of ternary complexes of K65R mutant RT dsDNA with TFV-DP or the natural substrate dATP. 2009 The Journal of biological chemistry Introduction HIV K65R 62 66 RT 74 76 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Interestingly, K65R also has a reduced rate of excision of NRTIs that is most pronounced for AZT and results in a counteraction of the incorporation and excision resistance mechanisms that restores full AZT susceptibility. 2009 The Journal of biological chemistry Introduction HIV K65R 15 19 NRTI 59 64 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R causes reduced susceptibility to TFV disoproxil fumarate and all other NRTIs with the exception of AZT. 2009 The Journal of biological chemistry Introduction HIV K65R 0 4 NRTI 76 81 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R emerges in response to treatment with tenofovir (TFV) disoproxil fumarate, abacavir, didanosine (ddI), or stavudine and has recently been shown to have increased frequency in subtype C HIV-1. 2009 The Journal of biological chemistry Introduction HIV K65R 0 4 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R is further able to discriminate against all NRTIs by having an even slower incorporation rate than the natural substrates. 2009 The Journal of biological chemistry Introduction HIV K65R 0 4 NRTI 49 54 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R results in a virus with reduced fitness that is attributed to a slower rate of incorporation (kpol) for the natural dNTP substrates. 2009 The Journal of biological chemistry Introduction HIV K65R 0 4 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Mutations M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N, which are primary resistance mutations for AZT and stavudine, are called thymidine analog mutations (TAMs), AZTr, or excision-enhancing mutations. 2009 The Journal of biological chemistry Introduction HIV D67N;K219E;K219N;K219Q;K70R;L210W;M41L;T215F;T215Y 16;48;48;48;22;28;10;35;35 20;57;57;57;26;33;14;42;42 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Q151M causes NRTI multidrug resistance that is often accompanied by several secondary mutations and termed the Q151M complex. 2009 The Journal of biological chemistry Introduction HIV Q151M;Q151M 111;0 116;5 NRTI 13 17 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Several modeling studies have proposed that the K65R mutation alters the positioning and binding of the NRTI-TP or surrounding amino acid residues or that the conformational mobility of the K65R-containing fingers loop is reduced, however, there is no universal agreement on the structural basis for the broad effects of the K65R mutation. 2009 The Journal of biological chemistry Introduction HIV K65R;K65R;K65R 48;190;325 52;194;329 NRTI 104 108 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R crystal structures presented here show how this mutation restricts the structural adaptability of the enzyme by forming a molecular platform involving the conserved residue Arg72; the platform may discriminate against the incorporation of NRTIs, interfere with the binding of ATP as an excision substrate, and interact with other NRTI resistance mutations. 2009 The Journal of biological chemistry Introduction HIV K65R 4 8 NRTI;NRTI 248;339 253;343 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The most relevant crystal structures available for analyzing K65R are of wild-type HIV-1 RT dsDNA in complexes with dTTP or TFV-DP. 2009 The Journal of biological chemistry Introduction HIV K65R 61 65 RT 89 91 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. These structures provide the basic framework for understanding DNA polymerization and binding of TFV-DP to RT, but they do not explain the effects of the K65R mutation on polymerization, excision, or TFV resistance. 2009 The Journal of biological chemistry Introduction HIV K65R 154 158 RT 107 109 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. confirmed this observation, several other groups did not find any association of the R77Q substitution with the prognosis of disease progression. 2009 PloS one Introduction HIV R77Q 85 89 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Nevertheless, an initial study has reported that a single substitution at the position Arg77 of HIV-1 Vpr (Arg77Gln) was found in a higher frequency in vpr alleles from long-term non-progressors (LTNPs) than in patients with AIDS. 2009 PloS one Introduction HIV R77Q 107 115 Vpr;Vpr 102;152 105;155 AIDS 225 229 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. HIV-1 carrying the substitution of Ala for Lys-273 grew like the WT in Jurkat T cells, dispensing an obvious role for this highly conserved tail residue in virus replication. 2009 Retrovirology Introduction HIV K273A 35 50 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. Thus, one goal of this study was to evaluate the solubility-enhancing F185K CCD mutation for its potential effects on the in vitro activities of tail deletion mutant enzymes. 2009 Retrovirology Introduction HIV F185K 70 75 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. A total of 13 mutations were initially identified as etravirine RAMs, including V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V and G190A/S (Table 5). 2008 Future HIV therapy Introduction HIV A98G;K101E;K101P;L100I;V90I 86;99;99;92;80 90;106;106;97;84 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. In a multivariate analysis, the total number of baseline NRTI and/or NNRTI mutations, and not K103N or Y181C in particular, predicted virologic response. 2008 Future HIV therapy Introduction HIV K103N;Y181C 94;103 99;108 NNRTI;NRTI 69;57 74;61 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. In vitro studies suggest that etravirine selects for L100I, V179F/I, Y181C, G190E, M230L and Y318F, which may contribute to etravirine resistance (FC >10). 2008 Future HIV therapy Introduction HIV G190E;M230L;Y181C;Y318F 76;83;69;93 81;88;74;98 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Initial drug development employed a parallel screening strategy of candidate compounds from the diarylpyrimidines, testing their activity against both wild-type HIV-1 as well as single and double mutants (including K101E + K103N and K103N + Y181C). 2008 Future HIV therapy Introduction HIV K101E;K103N;K103N;Y181C 215;223;233;241 220;228;238;246 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. More recently, further statistical analysis of the pooled 24-week DUET data expanded the original list of 13 etravirine RAMs to 17 with the addition of K101H, E138A, V179T and M23L (Table 5). 2008 Future HIV therapy Introduction HIV E138A;K101H;M23L;V179T 159;152;176;166 164;157;180;171 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Of the mutations that had most significantly affected response to etravirine in the DUET trials, Y181C was present in 17.5% of the isolates, G190S in less than 2.5%, and V179F was not found in any isolates. 2008 Future HIV therapy Introduction HIV G190S;V179F;Y181C 141;170;97 146;175;102 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Other in vitro mutations of unknown clinical significance include V189I, E194G, L234I and T386A. 2008 Future HIV therapy Introduction HIV E194G;L234I;T386A;V189I 73;80;90;66 78;85;95;71 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Patients with prior nevirapine exposure had significantly more etravirine RAMs (0.66 +- 0.92 vs 0.43 +- 0.78; p < 0.001) and a higher prevalence of the Y181C mutation (23.7 vs 8.7%; p < 0.001) than those who had used efavirenz. 2008 Future HIV therapy Introduction HIV Y181C 152 157 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. The inflexible chemical structure of older NNRTIs prevents them from interacting effectively with the viral reverse transcriptase once certain single mutations in the drugs binding pocket develop (particularly the K103N mutation). 2008 Future HIV therapy Introduction HIV K103N 214 219 RT;NNRTI 108;43 129;49 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. The mutations with the highest weights were Y181I and Y181V, followed by L100I, K101P, Y181C and M230L (Table 5). 2008 Future HIV therapy Introduction HIV K101P;L100I;M230L;Y181C 80;73;97;87 85;78;102;92 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. V90I, A98G/S, L100I, K101E/H/N/P/Q/R, K103H/N/R/S/T, V106A/I/M, V108I, E138A/G/K/Q, V179A/D/E/F/G/I/T, Y181C/F/I/V, Y188C/F/H/L, V189I, G190A/C/E/Q/R/S, H221Y, P225H, F227C/L, M230I/L, P236L, K238N/T, Y318F, N348I/T. 2008 Future HIV therapy Introduction HIV V108I 64 69 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Viral rebound correlated with baseline thymidine-associated mutations and/or M184V, as well as the number of baseline NNRTI mutations. 2008 Future HIV therapy Introduction HIV M184V 77 82 NNRTI 118 123 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. In solution, the intra-subunit salt-bridge between R87 and D29 was shown to be crucial for dimer stability of the mature PR; both the D29N and R87K mutants increased the dimer dissociation constant. 2010 Proteins Introduction HIV D29N;R87K 134;143 138;147 PR 121 123 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. Substitutions G86A and G86S were introduced into PR to construct mutants, termed PRG86A and PRG86S. 2010 Proteins Introduction HIV G86A;G86S 14;23 18;27 PR;PR;PR 49;81;92 51;83;94 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. The largest structural changes were observed in PRG86S/DRV at residues 66 through 69, correlating with significant side chain rearrangements in the alpha-helix. 2010 Proteins Introduction HIV G86S 50 54 PR 48 50 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. Thus, the mutation of R87K increases dissociation of the dimer resulting in drastically reduced catalytic activity. 2010 Proteins Introduction HIV R87K 22 26 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. We previously demonstrated that the R87 side chain is critical for the monomer-dimer equilibrium of the mature PR, and even a conservative mutation, R87K, drastically alters dimer formation. 2010 Proteins Introduction HIV R87K 149 153 PR 111 113 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. Our previous study of HIV-1 gag in a large HIV-1-infected cohort (N=431) identified three positively selected (PS) amino acids, V7I and I34L in the p17 region of gag (unpublished) and K403R in the p7 region of gag. 2010 Journal of immunological methods Introduction HIV I34L;K403R;V7I 136;184;128 140;189;131 Gag;Gag;Gag 28;162;210 31;165;213 HIV infections 43 57 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. The K403R mutation was found to be significantly associated with A*0301 after multiple test corrections in and following reanalysis of the raw data, the V7I and I34L mutations were also found to be associated with A*0301. 2010 Journal of immunological methods Introduction HIV I34L;K403R;V7I 161;4;153 165;9;156 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. This study sought to investigate post-partum drug resistance in ARV-naive women who received PLAT in the US between 1998 and 2005, using population-based sequencing of plasma virus and allele-specific PCR testing for the M184V, K103N and D30N mutations, associated with high-level resistance to lamivudine and emtricitabine, nevirapine and efavirenz, and nelfinavir, respectively. 2010 AIDS (London, England) Introduction HIV D30N;K103N;M184V 238;228;221 242;233;226 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Additionally, the major resistance mutations Q148H/RK and N155S have been shown to reduce replicative capacity. 2009 Antiviral therapy Introduction HIV N155S;Q148H;Q148K;Q148R 58;45;45;45 63;53;53;53 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Another pathway through Y143C has been described more recently. 2009 Antiviral therapy Introduction HIV Y143C 24 29 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Elvitegravir, which remains in the final stages of clinical development, is additionally associated with T66I and E92Q in primary resistance. 2009 Antiviral therapy Introduction HIV E92Q;T66I 114;105 118;109 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Major genetic pathways to integrase resistance, initially through N155H and shifting to Q148H/K/R-G140S or directly to Q148H/K/R-G140S, have been reported. 2009 Antiviral therapy Introduction HIV G140S;G140S;Q148H;Q148H;Q148K;Q148K;Q148R;Q148R;N155H 98;129;88;119;88;119;88;119;66 103;134;97;128;97;128;97;128;71 IN 26 35 19959414 The use of integrase inhibitors in treatment-experienced patients. A genotypic resistance test could be performed in 38 of these patients of whom 35 selected resistance mutations in the integrase gene following the N155H or the Q148H/R/K path almost always associated with one additional mutation. 2009 European journal of medical research Introduction HIV N155H;Q148H;Q148K;Q148R 148;161;161;161 153;170;170;170 IN 119 128 19959414 The use of integrase inhibitors in treatment-experienced patients. Overall, by week 96 resistance tests were available for 112 raltegravir treated patients of whom 73% had integrase mutations at one of the three positions (Y143C/H/R, Q148H/K/R N155H) almost always in combination with at least one other mutation. 2009 European journal of medical research Introduction HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 177;167;167;167;156;156;156 182;176;176;176;165;165;165 IN 105 114 19959414 The use of integrase inhibitors in treatment-experienced patients. The N155H or the Q148H/R/K alone are associated with high or intermediate levels of resistance that became of very high level when additional mutations are selected. 2009 European journal of medical research Introduction HIV N155H;Q148H;Q148K;Q148R 4;17;17;17 9;26;26;26 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. In studies where triple regimens of tenofovir, abacavir and lamivudine or tenofovir, didanosine and lamivudine were given to antiretroviral-naive subjects, the majority of subjects experiencing virological failure (VF) selected for M184V and K65R. 2010 The Journal of antimicrobial chemotherapy Introduction HIV K65R;M184V 242;232 246;237 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K65R can be selected in vivo by the drugs tenofovir and abacavir but its frequency appears to be highly dependent on the other drugs used within the regimen. 2010 The Journal of antimicrobial chemotherapy Introduction HIV K65R 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. M41L, D67N, K70R, L210W, T215F/Y and K219Q/E), such that they are rarely detected in vivo in the same sample by population sequencing. 2010 The Journal of antimicrobial chemotherapy Introduction HIV D67N;K219E;K219Q;K70R;L210W;T215F;T215Y;M41L 6;37;37;12;18;25;25;0 10;44;44;16;23;32;32;4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Prior HIV analysis by PG and by population phenotypic analysis of samples from COL40263 subjects with VF had demonstrated that selection of resistance via the TAM pathway was preferred to selection via the K65R pathway, suggesting that inclusion of zidovudine in the tenofovir/abacavir/lamivudine regimen could modulate selection to favour selection of TAMs. 2010 The Journal of antimicrobial chemotherapy Introduction HIV K65R 206 210 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. the mutation K65R and the thymidine analogue mutations (TAMs; i.e. 2010 The Journal of antimicrobial chemotherapy Introduction HIV K65R 13 17 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Using this more sensitive methodology we hoped to determine whether there was additional resistance to study drugs undetected by PG at baseline or at the time of VF that could have impacted the selection pathway, and whether the mutational antagonism between K65R and TAMs, as suggested by the in vitro data, would result in detection of clonal variants in these VF samples that would contain either K65R or TAMs, but not both. 2010 The Journal of antimicrobial chemotherapy Introduction HIV K65R;K65R 259;400 263;404 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. According to the International AIDS Society-USA drug resistance mutations update, the presence of 3 or more TAMs inclusive of M41L and L210W is expected to give a reduced in vivo response to tenofovir. 2010 AIDS (London, England) Introduction HIV L210W;M41L 135;126 140;130 AIDS 31 35 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Accordingly, at least 1 in 10 HIV infected individuals will have Y181C prior to etravirine exposure, particularly in patients failing first line antiretroviral therapies in resource poor settings due to the continued use of nevirapine. 2010 AIDS (London, England) Introduction HIV Y181C 65 70 HIV infections 30 42 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Accordingly, in this study we determined whether N348I alone, or in combination with TAMs or Y181C, decreased susceptibility to tenofovir or etravirine. 2010 AIDS (London, England) Introduction HIV N348I;Y181C 49;93 54;98 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Accordingly, the acquisition of N348I in HIV-1 RT may significantly impact both first and second line antiretroviral therapies in resource poor settings. 2010 AIDS (London, England) Introduction HIV N348I 32 37 RT 47 49 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. As reported previously, HIV-1 containing N348I conferred no significant increase in tenofovir EC50 compared to the corresponding WT strain (Table 1). 2010 AIDS (London, England) Introduction HIV N348I 41 46 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. By comparison, Y181C conferred 2.2-fold resistance to etravirine (p=0.02, n=4) while K103N did not confer a significant change in etravirine susceptibility compared to WT. 2010 AIDS (London, England) Introduction HIV K103N;Y181C 85;15 90;20 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. By contrast, when N348I was combined with Y181C, etravirine susceptibility was decreased 6.4-fold (p=0.02, n=4) relative to WT virus, and 2.9-fold (p=0.03, n=4) relative to Y181C HIV-1 (NL/181)(Table 1). 2010 AIDS (London, England) Introduction HIV N348I;Y181C;Y181C 18;42;173 23;47;178 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Consistent with this finding, the Y181C/N348I double mutation also significantly decreased etravirine susceptibility at the enzyme level (data not shown). 2010 AIDS (London, England) Introduction HIV N348I;Y181C 40;34 45;39 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Decreased susceptibility to tenofovir in vitro and in vivo is associated with the K65R mutation or the presence of three or more TAMs (e.g. 2010 AIDS (London, England) Introduction HIV K65R 82 86 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Furthermore, the prevalence of Y181C and K103N is 11% and 22%, respectively. 2010 AIDS (London, England) Introduction HIV K103N;Y181C 41;31 46;36 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. However, when combined with M41L and T215Y (NL/2AZT), N348I decreased tenofovir susceptibility by 1.7-fold (p=0.014, n=4) compared to WT. 2010 AIDS (London, England) Introduction HIV M41L;N348I;T215Y 28;54;37 32;59;42 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. In our study, N348I was selected by antiretroviral treatments that included AZT or the combination of AZT and nevirapine. 2010 AIDS (London, England) Introduction HIV N348I 14 19 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. In this regard, A371V and Q509L in the connection and RNase H domains, respectively, and mutations located at residues that form part of the RNase H primer grip potentiate resistance to tenofovir in cell culture based assays when combined with TAMs. 2010 AIDS (London, England) Introduction HIV A371V;Q509L 16;26 21;31 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. M41L and T215Y) and N348I, which may result in reduced in vivo drug efficacy. 2010 AIDS (London, England) Introduction HIV N348I;T215Y;M41L 20;9;0 25;14;4 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. N348I also increased tenofovir resistance when combined with M41L, L210W and T215Y (HX/3AZT) by 6.0-fold compared to WT (p= 0.009, n=5) and 3-fold compared to the HX/3AZT strain (p=0.008, n=4). 2010 AIDS (London, England) Introduction HIV L210W;M41L;T215Y;N348I 67;61;77;0 72;65;82;5 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. N348I has also been reported to confer resistance to didanosine and delavirdine and its emergence in a Japanese cohort was primarily associated with AZT and/or didanosine containing therapies. 2010 AIDS (London, England) Introduction HIV N348I 0 5 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. N348I is highly prevalent in RT inhibitor (RTI)-experienced patients, occurs early in therapy usually prior to the appearance of recognized thymidine analogue mutations (TAMs), and is associated with an increase in viremia. 2010 AIDS (London, England) Introduction HIV N348I 0 5 RT;RT 43;29 46;31 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. N348I is not a polymorphism. 2010 AIDS (London, England) Introduction HIV N348I 0 5 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. N348I was introduced by site directed mutagenesis into the background of wild-type (WT), K103N, Y181C, M41L/L210Y and M41L/L210W/T215Y expressing RT genes of the pNL4.3 (NL) or HXB-2 (HX) infectious molecular clones. 2010 AIDS (London, England) Introduction HIV L210W;M41L;T215Y;K103N;L210Y;M41L;Y181C;N348I 123;118;129;89;108;103;96;0 128;122;134;94;113;107;101;5 RT 146 148 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Our data (Table 1) demonstrate that N348I (NL/348) alone conferred a 1.6-fold decrease (p=0.019, n=4) in etravirine susceptibility compared to the corresponding WT strain. 2010 AIDS (London, England) Introduction HIV N348I 36 41 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Similarly, we have shown that N348I enhances resistance to etravirine in the context of Y181C, a mutation that is associated with reduced virological response in vivo. 2010 AIDS (London, England) Introduction HIV N348I;Y181C 30;88 35;93 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Since the presence of three or more NNRTI mutations V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V and G190A/S results in no response to etravirine treatment, the presence of two of these NNRTI mutations and N348I at baseline may also reduce etravirine efficacy in vivo. 2010 AIDS (London, England) Introduction HIV A98G;G190A;G190S;K101E;K101P;L100I;N348I;V106I;V179D;V179F;V90I;Y181C;Y181I;Y181V 58;110;110;71;71;64;215;80;87;87;52;96;96;96 62;117;117;78;78;69;220;85;94;94;56;105;105;105 NNRTI;NNRTI 36;195 41;200 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Surprisingly, etravirine activity is not compromised by the K103N mutation. 2010 AIDS (London, England) Introduction HIV K103N 60 65 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Taken together, our in vitro data warrant studies to determine the clinical significance of the appearance of a pre-existing N348I mutation in regimens containing tenofovir or etravirine. 2010 AIDS (London, England) Introduction HIV N348I 125 130 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Taken together, these data demonstrate that N348I confers a small decrease in susceptibility to etravirine and significantly potentiates etravirine resistance in the context of Y181C but not K103N. 2010 AIDS (London, England) Introduction HIV K103N;N348I;Y181C 191;44;177 196;49;182 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. Taken together, these data demonstrate that N348I decreases tenofovir susceptibility in the presence of TAMs, and notably this effect is observed with less than three TAMs. 2010 AIDS (London, England) Introduction HIV N348I 44 49 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. To date, it has not been established if N348I can reduce susceptibility to tenofovir or etravirine and compromise drug activity in treatment-experienced patients. 2010 AIDS (London, England) Introduction HIV N348I 40 45 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. We recently identified the N348I mutation in the connection domain of the human immunodeficiency type I (HIV-1) reverse transcriptase (RT) that confers resistance to both zidovudine (AZT) and nevirapine. 2010 AIDS (London, England) Introduction HIV N348I 27 32 RT;RT 112;135 133;137 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. When combined with K103N, no decrease in etravirine susceptibility was observed compared with K103N alone, while a small decrease in etravirine susceptibility was seen compared to WT (p=0.019, n=5)(Table 1). 2010 AIDS (London, England) Introduction HIV K103N;K103N 19;94 24;99 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. On the other hand, previous studies showed that continuation of lamivudine after emerging of the M184V mutation had somewhat benefit on immunological response and clinical progression in patients who had limited options of salvage regimens. 2009 AIDS research and therapy Introduction HIV M184V 97 102 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Furthermore, mutations in residue 170 Asparagine (N), located in the newly described surface contact of C3d, altered the interaction with CR2 in a competition binding assay. 2010 Immunology letters Introduction HIV N170N 34 52 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Two clusters of amino acid residues important for the C3d-CR2 interaction were identified (cluster I: 36 Aspartate (D), 37 Glutamate (E) and 39E; cluster II: 160E, 162 Lysine (K), 163D, 164 Isoleucine (I), 166E and 167E). 2010 Immunology letters Introduction HIV E37E;I164I;K162K 120;186;164 136;204;178 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. In comparison to wildtype Vpu, the S52A mutant was strongly impaired in its ability to counteract tetherin, permitting viral release only at low levels of tetherin expression. 2010 Retrovirology Introduction HIV S52A 35 39 Vpu 26 29 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. These results may explain why HIV-1 encoding S52A Vpu caused CD4+ T-cell depletion and replicated with wildtype-like efficiency in lymphoid cells and HLT ex vivo, but not in macrophages that express higher levels of tetherin. 2010 Retrovirology Introduction HIV S52A 45 49 Vpu 50 53 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Although it is a very new anti-HIV drug, raltegravir-resistant mutants of HIV integrase, such as E92Q/N155H and G140S/Q148H in the catalytic core domain, have already been identified in patients. 2010 Journal of molecular biology Introduction HIV E92Q;G140S;N155H;Q148H 97;112;102;118 101;117;107;123 IN 78 87 20096702 A dynamic model of HIV integrase inhibition and drug resistance. This protocol was used to create dynamic models of the wild type, E92Q/N155H, and G140S/Q148H drug-resistant mutants of the catalytic core domain of HIV integrase. 2010 Journal of molecular biology Introduction HIV E92Q;G140S;N155H;Q148H 66;82;71;88 70;87;76;93 IN 153 162 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Furthermore, the T477A compensatory substitution was also effective at restoring infectivity to some p51 RNH mutants that never recovered infectivity during repeated passage. 2010 Retrovirology Introduction HIV T477A 17 22 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. However, in one case, the recovered virus maintained the mutated protease recognition sequence (F440V), but now possessed a single additional amino acid substitution, T477A, distal to the normal the p51 RNH cleavage site between F440 and Y441. 2010 Retrovirology Introduction HIV F440V;T477A 96;167 101;172 PR 65 73 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In all cases, the addition of the T477A substitution resulted in virions containing seemingly wild-type levels of heterodimeric p66/p51 RT despite the continued presence of mutations in the p51 RNH protease recognition sequence. 2010 Retrovirology Introduction HIV T477A 34 39 PR;RT 198;136 206;138 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In the present work we examined in detail the effect of the conservative T477A substitution on alleviating the detrimental phenotypic effect of the F440V mutation in the p51 RNH protease recognition sequence. 2010 Retrovirology Introduction HIV F440V;T477A 148;73 153;78 PR 178 186 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Interestingly, the T477A substitution also alleviated the phenotypic impact of many other mutations in the p51 RNH cleavage region, despite the fact that this compensatory substitution did not normally arise in revertants of these mutant viruses. 2010 Retrovirology Introduction HIV T477A 19 24 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. We propose that when the p51 RNH junction is mutated, the T477A compensatory substitution may enable HIV-1 PR-mediated proteolytic processing of RT p66 at another site close to the normal proteolytic cleavage point, thereby enabling formation of an RT heterodimer refractory to additional proteolytic degradation. 2010 Retrovirology Introduction HIV T477A 58 63 PR;RT;RT 107;145;249 109;147;251 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Accordingly, in this study our primary goal was to analyze the effects of N348I on the AZT-MP excision phenotype using recombinant purified RTs that contained K70R, Y181C or K70R/Y181C. 2010 AIDS (London, England) Introduction HIV K70R;K70R;N348I;Y181C;Y181C 159;174;74;165;179 163;178;79;170;184 RT 140 143 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. By contrast, the N348I mutation in HIV-1 RT indirectly increases AZT resistance by decreasing the frequency of secondary ribonuclease H (RNase H) cleavages that significantly reduce the RNA/DNA duplex length of the template/primer (T/P) and diminish the efficiency of AZT-MP excision. 2010 AIDS (London, England) Introduction HIV N348I 17 22 RT 41 43 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. For example, substitutions at RT codons 44, 118, 207, 208 and 333 have been associated with increased AZT resistance in viruses that carry both TAMs and M184V. 2010 AIDS (London, England) Introduction HIV M184V 153 158 RT 30 32 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. From a clinical perspective, the efficacy of these regimens can also be attributed to a higher genetic barrier to resistance due to the ddI and 3TC resistance mutations (L74V and M184V, respectively) antagonizing the AZT-associated resistance mutations (e.g. 2010 AIDS (London, England) Introduction HIV L74V;M184V 170;179 175;184 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. However, recent investigations into the biochemical mechanisms by which N348I in RT confers AZT resistance raised additional questions as to whether this mutation may also compensate for the antagonism between TAMs and Y181C (described below). 2010 AIDS (London, England) Introduction HIV N348I;Y181C 72;219 77;224 RT 81 83 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Initially, we hypothesized that N348I was selected early in therapy failure because the mutation decreased susceptibility to both AZT and nevirapine and accordingly provided a simple genetic pathway to resistance that involved only a single nucleotide change. 2010 AIDS (London, England) Introduction HIV N348I 32 37 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. It is not known, however, if the Y181C mutation also antagonizes the N348I AZT resistance phenotype. 2010 AIDS (London, England) Introduction HIV N348I;Y181C 69;33 74;38 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. N348I appears early in therapy and was found to be highly associated with TAMs, M184V/I and the NNRTI resistance mutations K103N, Y181C/I, and G190A/S. 2010 AIDS (London, England) Introduction HIV G190A;G190S;K103N;M184I;M184V;Y181C;Y181I;N348I 143;143;123;80;80;130;130;0 150;150;128;87;87;137;137;5 NNRTI 96 101 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. N348I was also found to be significantly associated with therapies that contained AZT and nevirapine. 2010 AIDS (London, England) Introduction HIV N348I 0 5 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Recently, we identified the N348I mutation in HIV-1 RT that confers both AZT and NNRTI resistance. 2010 AIDS (London, England) Introduction HIV N348I 28 33 NNRTI;RT 81;52 86;54 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. The Y181C mutation directly antagonizes this ATP-mediated excision activity of RT containing TAMs. 2010 AIDS (London, England) Introduction HIV Y181C 4 9 RT 79 81 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. A composite retrospective analysis of data from patients receiving a TDF + ABC regimen revealed a success rate of 86% when the regimen contained AZT, compared with 62% when it did not, and no K65R mutations were observed in subjects on regimens containing AZT. 2009 HIV therapy Introduction HIV K65R 192 196 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. A synergistic fitness interaction has been observed for K65R and Y181C mutations. 2009 HIV therapy Introduction HIV K65R;Y181C 56;65 60;70 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. A total of four NRTI-containing regimens, including TDF coformulated Trizivir have been recently proposed as a more stable regimen that may offset the development of K65R, while representing TAM-sparing regimens. 2009 HIV therapy Introduction HIV K65R 166 170 NRTI 16 20 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Abacavir/3TC (Epzicom ; GlaxoSmithKline, NC, USA) with lopinavir has been used extensively as an alternate NRTI regimen with a favorable resistance profile that includes K65R. 2009 HIV therapy Introduction HIV K65R 170 174 NRTI;NC 107;41 111;43 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Accelerated risk for the development of K65R in the developing world. 2009 HIV therapy Introduction HIV K65R 40 44 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Although no direct head-to-head comparisons of subtype C versus B have been conducted clinically, the available data suggest that an HIV-1 subtype plays an associative role in the accelerated development of K65R resistance. 2009 HIV therapy Introduction HIV K65R 207 211 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Altogether, ddI, NVP and triple NRTI therapy may be associated with higher frequencies of selection of K65R. 2009 HIV therapy Introduction HIV K65R 103 107 NRTI 32 36 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. At least this way, K65R is not likely to be selected, even in the presence of Y181C and/or G190A, and AZT will remain active against M184V viruses. 2009 HIV therapy Introduction HIV G190A;K65R;M184V;Y181C 91;19;133;78 96;23;138;83 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Barrier to K65R selection is dependent on NRTI & NNRTI regimens. 2009 HIV therapy Introduction HIV K65R 11 15 NNRTI;NRTI 49;42 54;46 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Careful avoidance of coadministration of TDF with ABC or ddI in first-line treatment regimens and genotypic resistance testing for NNRTIs has led to decreasing trends in K65R appearance (<2% of the treated population) in the years following 2005. 2009 HIV therapy Introduction HIV K65R 170 174 NNRTI 131 137 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Cell culture studies, site-directed mutagenesis and enzymatic studies have begun to unravel the novel molecular mechanisms that may account for the more rapid appearance of K65R in subtype C. 2009 HIV therapy Introduction HIV K65R 173 177 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Clinical studies and large genotypic databases show a low incidence of K65R resistance in drug-naive and treatment-experienced patients. 2009 HIV therapy Introduction HIV K65R 71 75 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Development of K65R in subtype C occurred regardless of regimen, including TDF, d4T, ddI, ABC, TDF + 3TC and d4T + ddI. 2009 HIV therapy Introduction HIV K65R 15 19 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Facilitated development of K65R in non-B subtype infections. 2009 HIV therapy Introduction HIV K65R 27 31 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Highly potent TDF/FTC and ABC/3TC coformulated regimens with EFV or protease inhibitors prevent the advent of K65R resistance and are the drug combinations of choice in resource-rich settings. 2009 HIV therapy Introduction HIV K65R 110 114 PR 68 76 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In addition, AZT and d4T may also select for the more rarely observed Q151M nucleoside analog mutational (NAM) pathway (Q151M, A62V, V75I, F77L and F116Y), which confers broad-spectra NRTI resistance. 2009 HIV therapy Introduction HIV A62V;F116Y;F77L;Q151M;Q151M;V75I 127;148;139;70;120;133 131;153;143;75;125;137 NRTI 184 188 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In addition, high rates of virological failure have been observed for once-daily TDF/3TC/NVP regimens with K65R in subtype B and non-B subtype infections. 2009 HIV therapy Introduction HIV K65R 107 111 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In addition, there is a strong negative association of K65R with the M184V, L74V and K70E mutations, conferring resistance to 3TC/FTC, ddI and TDF, respectively. 2009 HIV therapy Introduction HIV K65R;K70E;L74V;M184V 55;85;76;69 59;89;80;74 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In addition, three single point mutations, K65R, Q151M and M184V, can confer high-level cross-class resistance to all commercially available NRTIs for HIV-2 infections. 2009 HIV therapy Introduction HIV K65R;M184V;Q151M 43;59;49 47;64;54 NRTI 141 146 HIV infections 151 167 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In several clinical studies involving a triple-NRTI regimen without AZT, 24-92% of patients identified as treatment failures had a virus with the K65R mutation. 2009 HIV therapy Introduction HIV K65R 146 150 NRTI 47 51 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In the case of the subtype C sequence, a homopolymeric stretch of adenine bases is present and ends at the exact nucleotide that is responsible for the AAG to AGG transition that gives rise to K65R. 2009 HIV therapy Introduction HIV K65R 193 197 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In this regard, retrospective analysis has revealed significant intersubtype differences in the acquisition of NVP resistance in mothers and infected children, involving K103N or Y181C in 69, 36, 19 and 21% of women with subtype C, D, A and CRF02_AG infections, respectively. 2009 HIV therapy Introduction HIV K103N;Y181C 170;179 175;184 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In this regard, the acquisition of resistance to NNRTIs is somewhat unique, in that single point mutations, including K103N, Y181C and V106M, arise within days or weeks and confer more than 100-1000-fold resistance. 2009 HIV therapy Introduction HIV K103N;V106M;Y181C 118;135;125 123;140;130 NNRTI 49 55 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Indeed, combining AZT with K65R-selecting drugs may be useful in preventing the evolution of K65R resistance. 2009 HIV therapy Introduction HIV K65R;K65R 27;93 31;97 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Indeed, the barrier to K65R selection is very low, requiring a single transition of AAG AGG in subtype C and, AAA AGA in subtype B and other non-C subtypes. 2009 HIV therapy Introduction HIV K65R 23 27 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Intensified virological response can be observed with K65R in the presence of the M184V mutation. 2009 HIV therapy Introduction HIV K65R;M184V 54;82 58;87 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Introduction of the 64/65 nucleotide polymorphisms of subtype C into subtype B HIV-1 accelerates the selection of the K65R mutation in subtype B to levels observed for subtype C. 2009 HIV therapy Introduction HIV K65R 118 122 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. K65R development in subtype C HIV-1. 2009 HIV therapy Introduction HIV K65R 0 4 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. K65R has been reported to occur in 20% of patients receiving TDF at some point during their treatment. 2009 HIV therapy Introduction HIV K65R 0 4 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. K65R reduces enzymatic excision of chain-terminating thymidine analogs. 2009 HIV therapy Introduction HIV K65R 0 4 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Moreover, recent findings in the COL40263 study looking at a ABC/3TC/ZDV + TDF-combined regimen, found that therapeutic failure was more likely to occur via the TAM pathway rather than K65R. 2009 HIV therapy Introduction HIV K65R 185 189 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Only one out of 90 patients who failed therapy in clinical studies using three or four NRTIs, which included AZT, had the K65R mutation and this person had received only once-daily AZT. 2009 HIV therapy Introduction HIV K65R 122 126 NRTI 87 92 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Preferential selection of K65R in subtype C HIV-1 may be attenuated by silent mutations at codons 70, 210 and 219, implicated in the TAM-resistance pathway. 2009 HIV therapy Introduction HIV K65R 26 30 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Resistance to TDF is rarely selected through the point mutation K65R (AAA AGA) in reverse transcriptase (RT). 2009 HIV therapy Introduction HIV K65R 64 68 RT;RT 82;105 103;107 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Similarly, a reduced selection of the K65R mutation was observed when AZT was added to an ABC-containing regimen. 2009 HIV therapy Introduction HIV K65R 38 42 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Single-genome sequence analysis demonstrates a negative association of K65R with TAMs (T215Y/F + >=2 TAMs) on the same genome, except when facilitated with Q151M complex mutations. 2009 HIV therapy Introduction HIV K65R;Q151M;T215F;T215Y 71;156;87;87 75;161;95;95 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Surprisingly, the development of K65R is strongly NRTI regimen-dependent. 2009 HIV therapy Introduction HIV K65R 33 37 NRTI 50 54 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. TAMs counterbalance K65R by decreasing enzymatic discrimination of d-nucleotide analogs and by increasing rates of nucleoside excision. 2009 HIV therapy Introduction HIV K65R 20 24 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Testing for minority K65R and M184V species using ultrasensitive allele-specific PCR may be important in ascribing the role of resistance in virological failure to K65R-selecting drugs. 2009 HIV therapy Introduction HIV K65R;K65R;M184V 21;164;30 25;168;35 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The 23% incidence of K65R in the Malawi study was associated with a d4T/3TC/NVP first-line regimen. 2009 HIV therapy Introduction HIV K65R 21 25 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The accumulation of secondary/compensatory mutations following acquisition of K65R is rare and quite distinct from the observed step-wise accumulation of TAMs. 2009 HIV therapy Introduction HIV K65R 78 82 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The DART studies in Uganda and Zimbabwe using TDF/3TC/AZT regimens show low K65R development. 2009 HIV therapy Introduction HIV K65R 76 80 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The development of K65R and Q151M may be facilitated for HIV-2 variants originating from West Africa (Senegal and Portugal), harboring NNRTI mutations (K101A, V106I, V179I, Y181I, Y188L and G190A) and TAMs/NAMs (T69N, V75I, V118I, L210N, T215S and K219E) as natural polymorphisms. 2009 HIV therapy Introduction HIV G190A;K101A;K219E;K65R;L210N;Q151M;T215S;T69N;V106I;V118I;V179I;V75I;Y181I;Y188L 190;152;248;19;231;28;238;212;159;224;166;218;173;180 195;157;253;23;236;33;243;216;164;229;171;222;178;185 NNRTI 135 140 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The development of K65R between subtypes may be explained by the nucleotide sequence dissimilarities that exist in subtype-specific templates (Figure 2). 2009 HIV therapy Introduction HIV K65R 19 23 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The first reported study demonstrated that 30% of Botswanan patients failing ddI- or d4T-based regimens developed K65R within 8 months of treatment. 2009 HIV therapy Introduction HIV K65R 114 118 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The higher propensity for K65R selection in subtype C, relative to other subtypes, may be related to differences in the poly-adenine stretches within the RT template spanning codons 63-68 (Figure 2). 2009 HIV therapy Introduction HIV K65R 26 30 RT 154 156 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The incidence of K65R in genotyped persons failing treatment was 7, 9, 14, 23 and 30% in clinical studies in Thailand, Senegal, South Africa, Malawi and Botswana, respectively. 2009 HIV therapy Introduction HIV K65R 17 21 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The K65R mutation is associated with reduced viral replication capacity and fitness, similar to the 3TC/FTC-associated M184V mutation - hallmarks that can be demonstrated at the enzymatic level. 2009 HIV therapy Introduction HIV K65R;M184V 4;119 8;124 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The K65R mutation is rarely selected with an overall incidence in 2-5% in genotyped patients, despite the increasing use of TDF and ABC since 2001. 2009 HIV therapy Introduction HIV K65R 4 8 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The K65R pathway may be associated with the NAM pathway, which is associated with the Q151M, A62V, V75I, F77L and F116Y mutations. 2009 HIV therapy Introduction HIV A62V;F116Y;F77L;K65R;Q151M;V75I 93;114;105;4;86;99 97;119;109;8;91;103 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The K65R resistance pathway has a favorable resistance profile conferring low- to intermediate-level phenotypic resistance to most NRTIs while hypersensitizing viruses to AZT. 2009 HIV therapy Introduction HIV K65R 4 8 NRTI 131 136 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The long duration of this study (36 months), as compared with the Thai, Kenyan and South African studies, clearly demonstrate the dangers of d4T-based regimens in accelerating the development of resistance, including the K65R pathway. 2009 HIV therapy Introduction HIV K65R 221 225 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The low incidence and high genetic barrier to K65R selection in drug-naive and treatment-experienced patients may be attributed to multiple factors including: impaired K65R viral replicative capacity, viral fitness constraints imposed by K65R in the presence of M184V - conferring resistance to 3TC and FTC, counter-selection of K65R- and TAM-resistance pathways, regimen potency and viral subtype (Figures 1 & 2). 2009 HIV therapy Introduction HIV K65R;K65R;K65R;K65R;M184V 46;168;238;329;262 50;172;242;333;267 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The low incidence and rapid disappearance of K65R is important with respect to second-line and salvage treatment options. 2009 HIV therapy Introduction HIV K65R 45 49 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The low incidence of the K65R mutation in drug-naive and treatment-experienced patients cannot be directly attributed to its' high genetic barrier. 2009 HIV therapy Introduction HIV K65R 25 29 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The M184V mutation can confer 0.7-1.0 log-fold diminution in viral load in the presence of other NRTIs. 2009 HIV therapy Introduction HIV M184V 4 9 NRTI 97 102 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The M184V mutation, conferring high-level resistance to 3TC and FTC, develops rapidly in approximately 50% of treated persons but remains a clinical benefit. 2009 HIV therapy Introduction HIV M184V 4 9 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The mechanism underlying the increased emergence of K65R and the unanticipated interaction between TDF + ABC and TDF + ddI, remain unclear. 2009 HIV therapy Introduction HIV K65R 52 56 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The most common coselected mutation is Q151M and the Q151M-NAM resistance pathway, which confers a reduced susceptibility to all NRTIs, with the exception of 3TC and TDF. 2009 HIV therapy Introduction HIV Q151M;Q151M 39;53 44;58 NRTI 129 134 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The mutation S68G appears to partially compensate for the replication defect associated with K65R. 2009 HIV therapy Introduction HIV K65R;S68G 93;13 97;17 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The presence of K65R and Q151M counter-selects M184V and confers more resistance than either of the single mutations alone. 2009 HIV therapy Introduction HIV K65R;M184V;Q151M 16;47;25 20;52;30 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The rapid selection of K65K/R and M184M/I/V as minority species emerging on separate clones underestimated resistance to TDF, ABC and ddI in phenotypic assays. 2009 HIV therapy Introduction HIV K65K;K65R;M184I;M184M;M184V 23;23;34;34;34 29;29;43;43;43 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The rapid selection of K65R in subtype C strains (AAG AGG), as compared with the slow evolution of K65R in subtype B (AAA AGA), cannot be explained by codon usage. 2009 HIV therapy Introduction HIV K65R;K65R 23;99 27;103 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The replicative compromise conferred by K65R is reflected by the strong selective pressure driving its rate of disappearance/reversion upon treatment interruption - K65R (1 month) > M184I/V (3 months) > TAMs (4-6 months) and Q151-NAMs (5.6 months). 2009 HIV therapy Introduction HIV K65R;K65R;M184I;M184V 40;165;182;182 44;169;189;189 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The rising incidence of K65R from 0.4 to 3.6% between 1998 and 2003 was linked to ddI therapy. 2009 HIV therapy Introduction HIV K65R 24 28 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The selection of K65R is negatively associated with K103N. 2009 HIV therapy Introduction HIV K103N;K65R 52;17 57;21 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The severe compromise in replicative fitness imposed by K65R contributes to the bidirectional phenotypic antagonism between K65R and TAM pathways. 2009 HIV therapy Introduction HIV K65R;K65R 56;124 60;128 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The slow rates of NVP clearance lead to a rapid appearance and retention of NNRTI mutations, which can facilitate the emergence of K65R resistance in developing countries where NVP is extensively used. 2009 HIV therapy Introduction HIV K65R 131 135 NNRTI 76 81 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The use of triple nucleoside analog combinations facilitates the selection of K65R. 2009 HIV therapy Introduction HIV K65R 78 82 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. There is clinical and tissue culture evidence to indicate an accelerated risk in developing the K65R mutation in subtype C infections. 2009 HIV therapy Introduction HIV K65R 96 100 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. There was a lower incidence of the K65R and L74V in ABC regimens containing AZT than in those without. 2009 HIV therapy Introduction HIV K65R;L74V 35;44 39;48 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. There was also a strong association for K65R selection with nevirapine (NVP) and the Y181C/G190A/S mutations associated with non-NRTI (NNRTI) resistance. 2009 HIV therapy Introduction HIV G190A;G190S;Y181C;K65R 91;91;85;40 98;98;90;44 NNRTI;NNRTI 125;135 133;140 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. These regimens may be suboptimal and fail to adequately achieve viral suppression, leading to a more rapid emergence of K65R resistance in non-B subtypes. 2009 HIV therapy Introduction HIV K65R 120 124 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. These studies were terminated after unexpectedly early failure rates (30-60%) occurred in association with K65R resistance. 2009 HIV therapy Introduction HIV K65R 107 111 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. This caveat of phenotypic assays should be recognized for K65R-selecting drugs, including TDF, ABC, d4T and ddI. 2009 HIV therapy Introduction HIV K65R 58 62 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. This drug combination led to rapid treatment failure by either K65R or TAM pathways. 2009 HIV therapy Introduction HIV K65R 63 67 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. This facilitated selection of K65R in subtype C is a grave concern, given that this subtype accounts for 50% of the worldwide pandemic. 2009 HIV therapy Introduction HIV K65R 30 34 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. This is based on viral regimen potency, intracellular half-life, single-drug dosing, the low risk of K65R development and a more favorable phenotypic resistance profile. 2009 HIV therapy Introduction HIV K65R 101 105 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. This second-generation NRTI showed improved antiviral activity against infections harboring TAMs (D67N, K70R and T215Y) and NAMs (Q151M). 2009 HIV therapy Introduction HIV D67N;K70R;Q151M;T215Y 98;104;130;113 102;108;135;118 NRTI 23 27 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Tissue culture selections of virus isolates from Botswana and Ethiopia confirmed the facilitated development of K65R in subtype C relative to subtype B. 2009 HIV therapy Introduction HIV K65R 112 116 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Two distinct TAM (TAM-1 and -2) pathways lead to the stepwise accumulation of major (M41L, K70R and T215Y/F), minor/secondary (D67N and L210W) and compensatory (E44D, V118I and H208Y) mutations that confer a 5-500-fold reduced susceptibility to AZT and broad cross-resistance between NRTIs (Figure 1). 2009 HIV therapy Introduction HIV D67N;E44D;H208Y;K70R;L210W;M41L;T215F;T215Y;V118I 127;161;177;91;136;85;100;100;167 132;165;182;95;141;89;107;107;172 NRTI 284 289 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Ultrasensitive PCR detection procedures identified minority NNRTI species (K103N or Y181C) in 70-87% of persons with subtype C, as compared with 42% of persons with subtype A/AE infections. 2009 HIV therapy Introduction HIV K103N;Y181C 75;84 81;89 NNRTI 60 65 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Virological failure was initially associated with the rapid emergence of M184V and K65R on separate viral genomes. 2009 HIV therapy Introduction HIV K65R;M184V 83;73 87;78 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Virological failure was linked to the synergistic selection of K65R, Y181C and/or G190A resistance. 2009 HIV therapy Introduction HIV G190A;K65R;Y181C 82;63;69 87;67;74 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Viruses harboring the K65R mutation show. 2009 HIV therapy Introduction HIV K65R 22 26 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. When subtype B RT was used to synthesize DNA on the subtype B template containing the K65 homopolymeric region, a ladder of pausing events was observed that started at codon 65 and ended at codon 67, which may be important for the selection of D67N associated with the TAM-1 pathway (Figure 2). 2009 HIV therapy Introduction HIV D67N 244 248 RT 15 17 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. When subtype C RT was used to synthesize DNA on the subtype C template containing the K65 homopolymeric region, strong pausing was seen at the exact nucleotide position responsible for K65R development. 2009 HIV therapy Introduction HIV K65R 185 189 RT 15 17 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. While M184V and K65R may prevail in patients, these mutations markedly compromise viral replicative capacity. 2009 HIV therapy Introduction HIV K65R;M184V 16;6 20;11 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. While one report disputed a facilitated selection of K65R in subtype C in early TDF trials, recent clinical studies demonstrates a higher incidence of K65R in subtype A and C infections receiving d4T- and ddI-based regimens. 2009 HIV therapy Introduction HIV K65R;K65R 53;151 57;155 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. While the K65R mutation is often considered the TDF resistance mutation, it also arises with other nucleoside analogs, including abacavir (ABC), didanosine (ddI), d4T and amdoxovir. 2009 HIV therapy Introduction HIV K65R 10 14 20227665 Flexible use of nuclear import pathways by HIV-1. CA mutant T54A/N57A efficiently delivers its viral genome to the nucleus of nondividing cells but fails to integrate. 2010 Cell host & microbe Introduction HIV N57A;T54A 15;10 19;14 Capsid 0 2 20227665 Flexible use of nuclear import pathways by HIV-1. For example, CA mutant Q63A/Q67A is impaired for nuclear entry and retains elevated levels of PIC-associated CA protein. 2010 Cell host & microbe Introduction HIV Q63A;Q67A 23;28 27;32 Capsid;Capsid 13;109 15;111 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Mutations at sites L33Q, V38E, Q40K, and Q41R are particularly detrimental (Table 1). 2010 Biochemistry Introduction HIV L33Q;Q40K;Q41R;V38E 19;31;41;25 23;35;45;29 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. A pseudo wild type protease, which bears six point mutations (Q7K, L33I, N37S, L63I, C67A, and C95A) compared to the NL4-3 protease, has been previously optimized for NMR and kinetic studies of protease maturation. 2010 Retrovirology Introduction HIV C67A;C95A;L33I;L63I;N37S;Q7K 85;95;67;79;73;62 89;99;71;83;77;65 PR;PR;PR 19;123;194 27;131;202 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Biochemical analyses indicate that the mature H69E protease displayed a slightly lower catalytic activity comparable to the wild type protease. 2010 Retrovirology Introduction HIV H69E 46 50 PR;PR 51;134 59;142 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. However, in vitro autoprocessing of H69E precursor is drastically delayed, suggesting that H69E mutation may interfere with productive folding of the precursor. 2010 Retrovirology Introduction HIV H69E;H69E 36;91 40;95 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Interestingly, H69E mutation in the context of NL4-3 derived protease only demonstrated a moderate inhibitory effect on protease maturation. 2010 Retrovirology Introduction HIV H69E 15 19 PR;PR 61;120 69;128 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Mutations Q7K, L33I, L63I minimize autoproteolysis; C67A and C95A prevent cysteine-thiol oxidation. 2010 Retrovirology Introduction HIV C67A;C95A;L33I;L63I;Q7K 52;61;15;21;10 56;65;19;25;13 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. In addition to previously described LEDGF/p75-binding defective IN mutants V165A, A179P, KR186,7AA, this study also identified several new IN mutants, including K159P, V176A and I203P, which reside in alpha4 to alpha6 helices of IN that lost the ability to bind to both chromatin and LEDGF/p75. 2010 Virology journal Introduction HIV A179P;I203P;K159P;V165A;V176A 82;178;161;75;168 87;183;166;80;173 IN;IN;IN 64;139;229 66;141;231 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Interestingly, we also found that several IN mutations, H171A, L172A and EH170,1AA, within the loop region 170EHLK173 of IN, impaired the interaction with LEDGF/p75, but retained chromatin binding ability. 2010 Virology journal Introduction HIV H171A;L172A 56;63 61;68 IN;IN 42;121 44;123 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Recently, by using a cell-based chromatin binding assay and co-immunoprecipitation (co-IP), we have identified three IN mutations (V165A, A179P, KR186,7AA) that impaired binding to host chromatin and LEDGF/p75. 2010 Virology journal Introduction HIV A179P;V165A 138;131 143;136 IN 117 119 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Only one study has identified a subject with intrinsic 4E10 resistance that correlated with a natural polymorphism in the epitope sequence (F673L), though another study identified phenotypically resistant virus without genotypic changes in the MPER regions. 2010 PloS one Introduction HIV F673L 140 145 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. As observed for the K65R variant, virus containing the L74V mutation remained sensitive to zidovudine. 2010 Antiviral therapy Introduction HIV K65R;L74V 20;55 24;59 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. DXG has shown good activity in vitro against HIV-1 strains resistant to lamivudine or emtricitabine (M184V/I) and strains containing zidovudine/stavudine-resistant thymidine analogue mutations (TAMs), including the 69SS double insert. 2010 Antiviral therapy Introduction HIV M184I;M184V 101;101 108;108 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. On the basis of the favourable mutational resistance mechanisms, counter-selection of K65R and TAMs, and synergistic antiviral activity, it is expected that coadministration of zidovudine with amdoxovir could delay the emergence of NRTI resistance and prolong treatment response. 2010 Antiviral therapy Introduction HIV K65R 86 90 NRTI 232 236 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. Previous reports suggest that the K65R mutation, which confers cross-resistance to DXG and amdoxovir, can revert zidovudine-resistant virus to zidovudine-sensitive virus. 2010 Antiviral therapy Introduction HIV K65R 34 38 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. Retrospective analyses of clinical databases of patient genotypes also demonstrate the negative association of K65R with specific TAMs. 2010 Antiviral therapy Introduction HIV K65R 111 115 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. Selection studies showed a delayed emergence of HIV-1-resistant viruses to DXG, which was associated with K65R or L74V mutations in MT-2 cells. 2010 Antiviral therapy Introduction HIV K65R;L74V 106;114 110;118 20386073 Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. The bidirectional phenotypic antagonism between the K65R and TAM pathways has been elucidated previously, demonstrating that K65R reduces the enzymatic excision of chain-terminating analogues, such as zidovudine, and that TAMs counteract K65R-mediated resistance by reducing the selectivity of the virus to incorporate natural substrate over the nucleoside analogue. 2010 Antiviral therapy Introduction HIV K65R;K65R;K65R 52;125;238 56;129;242 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K101E and G190S are also of interest because they are associated with HIV-1 resistance to the next-generation NNRTI, etravirine (Picchio, G., Vingerhoets, J., Staes, M., Tambuyzer, L., Bacheler, L., Pattery, T., de Bethune, M. 2010 Virology Introduction HIV G190S;K101E 10;0 15;5 NNRTI 110 115 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K101E has been observed in patients failing NNRTIs, including EFV, and most often occurs in combination with other known NNRTI-resistance mutations. 2010 Virology Introduction HIV K101E 0 5 NNRTI;NNRTI 44;121 50;126 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K101E in combination with either K103N or G190S increases EFV resistance more than 10-fold. 2010 Virology Introduction HIV G190S;K103N;K101E 42;33;0 47;38;5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K103N is the most frequently observed NNRTI-resistance mutation in patients failing EFV-containing regimens. 2010 Virology Introduction HIV K103N 0 5 NNRTI 38 43 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. One example of this type of mutation is L74V, which confers resistance to the nucleoside analogs abacavir and didanosine and improves the replication fitness of the NNRTI-resistant mutants G190E and K103N+L100I. 2010 Virology Introduction HIV G190E;K103N;L100I;L74V 189;199;205;40 194;204;210;44 NNRTI 165 170 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Other NNRTI resistance mutations, such as G190S, confer similar or greater degrees of EFV resistance compared to K103N, but develop uncommonly in patient isolates. 2010 Virology Introduction HIV G190S;K103N 42;113 47;118 NNRTI 6 11 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Uncommonly occurring NNRTI resistance mutations introduced into a laboratory strain cause substantially greater reductions in replication fitness than K103N, as measured in cell culture in the absence and presence of drug, suggesting that replication fitness influences the likelihood of a mutant emerging during treatment failure of an NNRTI-containing regimen. 2010 Virology Introduction HIV K103N 151 156 NNRTI;NNRTI 21;337 26;342 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We further explored the effects of K101E on HIV-1 replication fitness and EFV resistance alone and in combination with G190S, and evaluated the ability of other RT mutations to modulate these effects. 2010 Virology Introduction HIV G190S;K101E 119;35 124;40 RT 161 163 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Specific polymorphisms at SP1 residues 7 and 8 (SP1-V7A, -V7M, -T8Delta and -T8N) were shown to be sufficient to confer decreased BVM susceptibility, while other mutations at SP1 residues 6 and 8 (SP1-Q6A, -Q6H and -T8A) retained sensitivity. 2010 Retrovirology Introduction HIV Q6H;T8A;T8N;V7M;Q6A;V7A 207;216;77;58;201;52 210;219;80;61;204;55 SP1;SP1;SP1;SP1 26;48;175;197 29;51;178;200 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The in vitro selected BVM-resistance mutations map to three highly conserved residues at the extreme C-terminus of CA (CA-H226Y, L231M and L231F) and the first and third residues of SP1 (SP1-A1V, A3V and A3T). 2010 Retrovirology Introduction HIV A1V;A3T;A3V;H226Y;L231F;L231M 191;204;196;122;139;129 194;207;199;127;144;134 SP1;SP1;Capsid;Capsid 182;187;115;119 185;190;117;121 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In a previous work, we reported how patients who had failed to respond to therapies under RAL-containing regimens presented the N155H mutation, which was then replaced over time by the Y143C/H/R mutations. 2010 PloS one Introduction HIV N155H;Y143C;Y143H;Y143R 128;185;185;185 133;194;194;194 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In vitro, several mutations have been introduced into the IN gene and activities of mutants have been determined (T66I, L74M, E92Q, F121Y, Q148K, S153Y, N155H). 2010 PloS one Introduction HIV E92Q;F121Y;L74M;N155H;Q148K;S153Y;T66I 126;132;120;153;139;146;114 130;137;124;158;144;151;118 IN 58 60 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Q148H is rescued by the G140S mutation. 2010 PloS one Introduction HIV G140S;Q148H 24;0 29;5 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The most frequent primary RAL resistance mutations emerging in vivo at virological failure (VF) in the IN gene are Q148H/R/K, N155H, and to a lesser extent Y143C/H/R. 2010 PloS one Introduction HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 126;115;115;115;156;156;156 131;124;124;124;165;165;165 IN 103 105 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The Q148H mutation, which leads to a decreased activity of IN, confers a higher level of resistance to RAL than G140S or N155H. 2010 PloS one Introduction HIV G140S;N155H;Q148H 112;121;4 117;126;9 IN 59 61 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. We describe here the genetic pathways and the dynamics of emergence of the Y143C/R mutations in HIV-1 integrase, and the impact of these mutations on the enzymatic functions of the integrase in the presence or absence of RAL. 2010 PloS one Introduction HIV Y143C;Y143R 75;75 82;82 IN;IN 102;181 111;190 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Here we have begun to explore the biological basis for conservation of V3 sequence by creating an I309L substitution in a panel of eleven diverse, patient-derived subtype C Envs that includes recently transmitted viruses and defined autologous Nab escape variants. 2010 Virology Introduction HIV I309L 98 103 Env 173 177 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Standard population genotyping identified M184V/I in all participants, but K65R in only 10/20. 2010 Antiviral therapy Introduction HIV K65R;M184I;M184V 75;42;42 79;49;49 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. (1)) retains activity against HIV-1 containing the single key NNRTI mutations K103N, V106A or L100I. 2010 Letters in drug design & discovery Introduction HIV K103N;L100I;V106A 78;94;85 83;99;90 NNRTI 62 67 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. For example, the G190E mutations introduce a bulky side-chain which may prevent NNRTI binding by sterically interfering with functional groups, such as the cyclopropyl ring of nevirapine. 2010 Letters in drug design & discovery Introduction HIV G190E 17 22 NNRTI 80 85 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. For example, the Y181C mutation eliminates pi-stacking interactions between this residue and the aromatic ring of the NNRTI pharmacophore. 2010 Letters in drug design & discovery Introduction HIV Y181C 17 22 NNRTI;PI 118;43 123;45 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. Mutations associated with resistance to NNRTIs include L100I, K101E, K103N, V106A, V108I, V179D, Y181C, Y188C/L/H, G190A/E/S, M230L, P236L and Y318F. 2010 Letters in drug design & discovery Introduction HIV G190A;G190E;G190S;K101E;K103N;L100I;M230L;P236L;V106A;V108I;V179D;Y181C;Y188C;Y188H;Y188L;Y318F 115;115;115;62;69;55;126;133;76;83;90;97;104;104;104;143 124;124;124;67;74;60;131;138;81;88;95;102;113;113;113;148 NNRTI 40 46 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. The N-aminoimidazoles (NAIMs) have also been reported to inhibit replication of the WT virus as well as an HIV-1 strain that contained both the K103N and Y181C mutations. 2010 Letters in drug design & discovery Introduction HIV K103N;Y181C 144;154 149;159 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Our results revealed that correct dNTP insertion was enhanced over incorrect for the K65A mutant via a decreased incorporation efficiency for the incorrect dNTP. 2010 Journal of molecular biology Introduction HIV K65A 85 89 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. We, and others, have previously demonstrated that deletion of the entire beta3- beta4 loop, or a K65A substitution, leads to an increased fidelity through an increase in dNTP selection stringency. 2010 Journal of molecular biology Introduction HIV K65A 97 101 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. (ii) Observational studies have suggested that K65R emerges in a higher proportion of individuals infected with subtype C who develop virologic failure following combination antiretroviral (ARV) therapy than in those infected with subtype B viruses. 2010 PloS one Introduction HIV K65R 47 51 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. (iii) Two laboratories have described preferential RT pausing at the nucleotide position responsible for the AAG-to-AGG K65R mutation during positive-strand DNA synthesis of a subtype C, but not a subtype B, nucleotide template . 2010 PloS one Introduction HIV K65R 120 124 RT 51 53 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. (iii) Two laboratories have described preferential RT pausing at the nucleotide position responsible for the AAG-to-AGG K65R mutation during positive-strand DNA synthesis of a subtype C, but not a subtype B, nucleotide template. 2010 PloS one Introduction HIV K65R 120 124 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The HIV-1 reverse transcriptase (RT) mutation K65R is one of the most important HIV-1 drug resistance mutations. 2010 PloS one Introduction HIV K65R 46 50 RT;RT 10;33 31;35 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Three lines of evidence suggest that K65R may be more likely to emerge in subtype C than subtype B viruses from individuals with virologic failure: (i) K65R has been reported to emerge more rapidly during in vitro passage of subtype C than in subtype B viruses in the presence of tenofovir. 2010 PloS one Introduction HIV K65R;K65R 37;150 41;156 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. We performed ultra-deep pyrosequencing (UDPS; 454 Life Sciences/Roche, Branford, CT) to ascertain whether K65R can be detected in minority HIV-1 variants from ARV-naive individuals infected with subtype C viruses. 2010 PloS one Introduction HIV K65R 106 110 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. In our screening, 2 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR, with IC50 values of 0.46, 1.52, and 1.45 nM respectively. 2010 Bioorganic & medicinal chemistry letters Introduction HIV K101E 99 104 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. In the further evaluation of 2, we discovered that it retained its nanomolar activity against drug-resistant HIV strains including NL4-3 (K101E) and RTMDR (Table 2). 2010 Bioorganic & medicinal chemistry letters Introduction HIV K101E 138 143 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. K101E tends to decrease viral susceptibility to all nucleoside RT inhibitors, while RTMDR is a multiple RT inhibitor-resistant strain, which is insensitive to AZT, ddI, nevirapine, and other NNRTIs. 2010 Bioorganic & medicinal chemistry letters Introduction HIV K101E 0 5 NNRTI;RT;RT 191;63;104 197;65;106 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. In this study, the binding of DRV was investigated with wild-type HIV-1 protease and two drug-resistant variants: FLAP+ (Figure 1B) with L10I, G48V, I54V, V82A which are a combination of flap and active site mutations, and ACT (Figure 1C) with V82T, I84V which are active site mutations. 2010 Journal of chemical theory and computation Introduction HIV G48V;I54V;I84V;L10I;V82A;V82T 143;149;250;137;155;244 147;153;254;141;159;248 PR 72 80 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. As the name indicates these mutations are usually seen in patients who have failed and later interrupted therapy with zidovudine (AZT) or stavudine (d4T), which leads to "reversion" of the resistance mutations T215Y and T215F, but nothing precludes that they may be present as minority variants before therapy. 2010 PloS one Introduction HIV T215F;T215Y 220;210 225;215 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. This region includes the following important and well-defined drug resistance mutations to nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs): L210W, T215Y/F and K219Q/E associated with resistance to zidovudine (AZT) and stavudine (d4T); M184I/V associated with resistance to lamivudine (3TC) and emtricitabine (FTC); and Y181C/I/V, Y188C/L/H and G190S/A associated with resistance to nevirapine (NVP), efavirenz (EFV) and etravirin (ETR). 2010 PloS one Introduction HIV G190A;G190S;K219E;K219Q;L210W;M184I;M184V;T215F;T215Y;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 371;371;186;186;167;262;262;174;174;346;346;346;357;357;357 378;378;193;193;172;269;269;181;181;355;355;355;366;366;366 NNRTI;NRTI;RT;RT 158;117;102;143 164;122;104;145 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Thus, only M184I, T215A and T215I were found at very low levels. 2010 PloS one Introduction HIV M184I;T215A;T215I 11;18;28 16;23;33 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. We also studied so called T215 reversion mutations (T215A/C/D/E/G/H/I/L/N/S/V). 2010 PloS one Introduction HIV T215A;T215C;T215D;T215E;T215G;T215H;T215I;T215L;T215N;T215S;T215V 52;52;52;52;52;52;52;52;52;52;52 77;77;77;77;77;77;77;77;77;77;77 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Data from clinical trials show that RAL resistance involves IN mutations Y143C, Q148H or R or K or N155H, together with associated secondary mutations that result in higher levels of resistance. 2010 Journal of acquired immune deficiency syndromes (1999) Introduction HIV N155H;Q148H;Y143C 99;80;73 104;85;78 IN 60 62 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The N155H mutant generally emerges first, and is eventually replaced by Q148H mutants, usually in combination with G140S. 2010 Journal of acquired immune deficiency syndromes (1999) Introduction HIV G140S;N155H;Q148H 115;4;72 120;9;77 20655872 Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. Recently, there has been interest in the A18H mutant of Vpu, viral protein 'u' of HIV-1, that induces highly selective H+ conductance not present in the wild type and that is blocked by rimantadine. 2011 Biochimica et biophysica acta Introduction HIV A18H 41 45 Vpu 56 59 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Conservative mutations of hydrophobic residues are common in PI resistance, including V32I, I50V, I54V/M, I84V and L90M that are the focus of this study. 2010 The FEBS journal Introduction HIV I50V;I54M;I54V;I84V;L90M;V32I 92;98;98;106;115;86 96;104;104;110;119;90 PI 61 63 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Drug resistant mutations V32I, I50V, I54V/M, and I84V belong to the inner cluster around the active site, while L90M is in the outer cluster. 2010 The FEBS journal Introduction HIV I50V;I54M;I54V;I84V;L90M;V32I 31;37;37;49;112;25 35;43;43;53;116;29 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. I54V in combination with other mutations, especially V82A, decreases the susceptibility to PI therapy. 2010 The FEBS journal Introduction HIV V82A;I54V 53;0 57;4 PI 91 93 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. I84V, which is located in the active site cavity, significantly reduces drug susceptibility to APV. 2010 The FEBS journal Introduction HIV I84V 0 4 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. L90M is commonly found during PI treatment and is resistant to all currently used PIs, with major effects on NFV and SQV. 2010 The FEBS journal Introduction HIV L90M 0 4 PI;PI 30;82 32;85 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Multi-drug-resistant mutation V32I, which alters a residue in the active site cavity, appears in about 20% of patients treated with APV and is associated with high levels of drug resistance to lopinavir (LPV)/ritonavir. 2010 The FEBS journal Introduction HIV V32I 30 34 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Mutation I54V appears in resistance to IDV, LPV, nelfinavir (NFV) and SQV. 2010 The FEBS journal Introduction HIV I54V 9 13 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. PR with mutation I50V shows 9-fold worse inhibition by DRV relative to wild type enzyme, and 50- and 20- fold decreased inhibition by indinavir (IDV) and SQV. 2010 The FEBS journal Introduction HIV I50V 17 21 PR 0 2 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Unlike Ile50, Ile54 does not directly interact with APV, but mutations of Ile54 are frequent in APV resistance and the I54M mutation causes 6-fold increased IC50. 2010 The FEBS journal Introduction HIV I54M 119 123 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. In fact several biochemical defects in the M184I mutant RT have been reported. 2010 Virology Introduction HIV M184I 43 48 RT 56 58 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Structural studies also demonstrated that the M184I mutation alters the template-primer interactions of RT, which explains its reduced processivity. 2010 Virology Introduction HIV M184I 46 51 RT 104 106 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. The beta-branched side chain of isoleucine in M184I reduces the binding affinity of RT for dNTP substrates and raises its Kd approximately 50-fold (from 1 microM of WT RT Kd to 56 microM). 2010 Virology Introduction HIV M184I 46 51 RT;RT 84;168 86;170 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. The HIV-1 vectors harbored the RT mutants, V148I and Q151N, which are defective in binding to dNTPs and thus fail to synthesize proviral DNA in cells with low dNTP concentrations, such as macrophages. 2010 Virology Introduction HIV Q151N;V148I 53;43 58;48 RT 31 33 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. The transient nature of the M184I mutation is likely due to its limited replicational fitness, compared to the M184V mutation. 2010 Virology Introduction HIV M184I;M184V 28;111 33;116 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. This RT mutation appears consistently in 3TC therapy, and ultimately results in a M184V mutation. 2010 Virology Introduction HIV M184V 82 87 RT 5 7 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Thus M184I RT exhibits a severely decreased activity at low dNTP concentrations, whereas M184V RT, which displays WT levels of dNTP binding affinity, remains enzymatically active at both the low and high dNTP concentrations found in macrophages and activated CD4+ T cells, respectively. 2010 Virology Introduction HIV M184I;M184V 5;89 10;94 RT;RT 11;95 13;97 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Thus, it would be reasonable to assume that the cPPT becomes more critical for HIV-1 replication in macrophages where the viral replication kinetics are slow due to limited dNTP pools, and during the delayed replication of HIV-1 vector containing partially defective RT mutations such as Q151N and V148I. 2010 Virology Introduction HIV Q151N;V148I 288;298 293;303 RT 267 269 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. We have identified a specific compensatory relationship between the viral resistance of M184I HIV-1 RT and its dependence on the cPPT and cellular dNTP concentrations. 2010 Virology Introduction HIV M184I 88 93 RT 100 102 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. We generated the SVGmu-pseudotyped lentiviral vectors packaged with the defective integrase containing a D64V point mutation. 2010 Vaccine Introduction HIV D64V 105 109 IN 82 91 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. A third pathway having a Y143R/C mutation has been observed in a smaller patient population. 2010 Biochemistry Introduction HIV Y143C;Y143R 25;25 32;32 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. HIV-1 containing the N155H mutation has a similar replication capacity (~70%) of wild type (wt) HIV-1. 2010 Biochemistry Introduction HIV N155H 21 26 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In most patients, mutations in IN responsible for RAL failure are represented in two independent genetic pathways; N155H and Q148H/R/K accounting for a severe loss (10-25 fold) in susceptibility to RAL with additional secondary mutations. 2010 Biochemistry Introduction HIV N155H;Q148H;Q148K;Q148R 115;125;125;125 120;134;134;134 IN 31 33 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In the patients enrolled for elvitegravir (EVG) studies, T66I, E92Q, Q148R and N155H mutations are primary contributors to EVG resistance. 2010 Biochemistry Introduction HIV E92Q;N155H;Q148R;T66I 63;79;69;57 67;84;74;61 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. We established that MK-2048 is equally active against IN possessing the RAL resistant N155H mutation in comparison to wt IN. 2010 Biochemistry Introduction HIV N155H 86 91 IN;IN 54;121 56;123 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. With N155H IN, the assembly of SC and concerted integration were delayed relative to wt IN suggesting a possible biochemical mechanism why IN is partially defective in HIV-1 possessing this mutation. 2010 Biochemistry Introduction HIV N155H 5 10 IN;IN;IN 11;88;139 13;90;141 20852643 Structural basis of HIV-1 resistance to AZT by excision. The mutations commonly associated with excision-mediated AZT resistance are M41L, D67N, K70R, L210W, T215Y, T215F, K219Q and K219E. 2010 Nature structural & molecular biology Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 94;137;127;100;106;76;120;113 98;142;132;104;111;80;125;118 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. In addition we showed that IIQ/VTR83-85 and T89A substitutions in the pNL4.3-Vpr77-92 sequence, inhibits PP2A1 binding and apoptosis. 2010 PloS one Introduction HIV T89A 44 48 Vpr 77 80 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. A single dose of NVP administered during delivery in pregnant women to prevent mother from transmitting HIV to their babies was able to select K103N mutant strains, which could persist as minority quasispecies for as long as five years after drug exposure. 2009 Journal of medical case reports Introduction HIV K103N 143 148 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Although selection of the K103N mutation is associated with moderately but significantly reduced in vitro fitness, strains bearing K103N in vivo tend to persist even in the absence of additional drug pressure. 2009 Journal of medical case reports Introduction HIV K103N;K103N 26;131 31;136 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. As efavirenz (EFV) and nevirapine (NVP) have a much longer plasma half-life than their companion nucleoside reverse transcriptase inhibitors (NRTIs), residual NNRTI monotherapies associated with structured or non-structured therapy interruptions may favor K103N selection. 2009 Journal of medical case reports Introduction HIV K103N 256 261 NRTI;NNRTI;NRTI 97;159;142 129;164;147 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. First generation NNRTIs have a low genetic barrier and the K103N mutation is able to confer class resistance after selection. 2009 Journal of medical case reports Introduction HIV K103N 59 64 NNRTI 17 23 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. In this report, we describe the case of a 55-year-old HIV-infected man, for whom a quickly selected and long-term persisting K103N mutation was detected after a time of exposure to EFV as short as three weeks. 2009 Journal of medical case reports Introduction HIV K103N 125 130 HIV infections 54 66 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. K103N persistence, however, is more frequently observed as a minority quasispecies, often undetectable in GRT (Genotypic antiretroviral Resistance Testing) assays performed at standard conditions. 2009 Journal of medical case reports Introduction HIV K103N 0 5 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Persistence of NNRTI-induced mutations, and particularly persistence of the K103N mutation, has also been observed in patients on treatment interruptions after failure of NNRTI-based regimens, as well as in patients on failing protease inhibitor (PI)-based regimens after previous NNRTI failures. 2009 Journal of medical case reports Introduction HIV K103N 76 81 PR;NNRTI;NNRTI;NNRTI;PI 227;15;171;281;247 235;20;176;286;249 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. The K103N bearing strain persisted as the dominant quasispecies for over three years in the absence of any further drug pressure, as documented by a GRT assay performed at the end of a long-lasting treatment interruption. 2009 Journal of medical case reports Introduction HIV K103N 4 9 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. In HIV-1-infected patients failing an INI-containing regimen, three distinct resistance pathways involving Y143R, Q148H/R/K or N155 H have been described. 2010 Retrovirology Introduction HIV N155H;Q148H;Q148K;Q148R;Y143R 127;114;114;114;107 133;123;123;123;112 IN 38 41 HIV infections 3 17 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. RAL resistance is not well documented for HIV-2, although cases of therapy failure have been associated with the emergence of variants carrying the Y143C, Q148K/R, or N155 H mutations, including Y143Y+T97A or Q148K, or Q148R+G140 S. 2010 Retrovirology Introduction HIV G140S;N155H;Q148K;Q148K;Q148R;Q148R;T97A;Y143C;Y143Y 225;167;155;209;155;219;201;148;195 231;173;162;214;162;224;205;153;200 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The N155 H substitution in conjunction with secondary mutations conferred HIV-2 strains a 37-fold increase in RAL IC50 , suggesting that HIV-2 can embrace the N155 H resistance pathway, although recent data suggest that this mutational pathway might be favored in the IN context of group B strains. 2010 Retrovirology Introduction HIV N155H;N155H 4;159 10;165 IN 268 270 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The Q148 H mutation in combination with the G140 S secondary mutation confers the highest level of resistance to RAL (> 1000-fold) together with the highest replicative capacity in vitro . 2010 Retrovirology Introduction HIV G140S;Q148H 44;4 50;10 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Resistance to ENF occurs due to amino acid substitutions within the HR-1 region of gp41 at amino acids 36-45 of HIV-1 gp41 with G36D, G36S, G36V, G36E, V38A, V38M, V38E, Q40H, N42T, and N43D being the most common ENF resistant mutations. 2010 PLoS computational biology Introduction HIV G36D;G36E;G36S;G36V;N42T;N43D;Q40H;V38A;V38E;V38M 128;146;134;140;176;186;170;152;164;158 132;150;138;144;180;190;174;156;168;162 gp41;gp41 83;118 87;122 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. We consider only the V38A mutant because this single substitution in HIV-1 gp41 is the most frequently observed in drug resistant virus and data on the population size of mutants with V38A are available. 2010 PLoS computational biology Introduction HIV V38A;V38A 21;184 25;188 gp41 75 79 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. However, in vitro studies have suggested that acyclovir may directly inhibit HIV-1 replication, with acyclovir exposure selecting for a single-base pair mutation in HIV-1 reverse transcriptase (RT) that results in an amino acid substitution at codon 75 (V75I) that confers resistance to the anti-HIV-1 effect of acyclovir. 2011 The Journal of infectious diseases Introduction HIV V75I 254 258 RT;RT 171;194 192;196 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. Two other mutations (T69N and M184I) were also detected in a minority of sequences in these in vitro experiments. 2011 The Journal of infectious diseases Introduction HIV M184I;T69N 30;21 35;26 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. Using a highly-sensitive oligonucleotide ligation assay (OLA), we screened for the V75I mutation in plasma samples from 168 HIV-1 infected persons from Botswana, Kenya, Peru, and the US exposed to daily acyclovir or valacyclovir for periods of 8 weeks to 24 months. 2011 The Journal of infectious diseases Introduction HIV V75I 83 87 HIV infections 124 138 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Several of the Vpu mutants tested (Vpu-I17A, -A18F, -W22L, and -S23L) effectively co-localized with BST-2, enhanced virion release, and down-regulated BST-2 from the cell surface. 2011 Virology Introduction HIV A18F;I17A;S23L;W22L 46;39;64;53 50;43;68;57 Vpu;Vpu 15;35 18;38 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The Vpu mutant A18H inefficiently enhanced virion release, inefficiently down-regulated BST-2 from the cell surface, appeared to be trapped in the ER, and co-localized poorly with BST-2, although it was able to down-regulate CD4 from the cell surface. 2011 Virology Introduction HIV A18H 15 19 Vpu 4 7 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Two of these mutants, Vpu-W22L and -S23L, were previously evaluated for their ion channel activity. 2011 Virology Introduction HIV S23L;W22L 36;26 40;30 Vpu 22 25 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-S23L was reportedly defective, indicating that ion channel activity may be unrelated to BST-2 antagonism. 2011 Virology Introduction HIV S23L 4 8 Vpu 0 3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. We could recapitulate the A18H phenotype in the case of wild type Vpu using the fungal metabolite brefeldin A (BFA) to block egress of Vpu from the ER, or by appending an ER-retention signal to the C-terminus of Vpu. 2011 Virology Introduction HIV A18H 26 30 Vpu;Vpu;Vpu 66;135;212 69;138;215 21248851 Atomic-level modelling of the HIV capsid. Elimination of the charge is expected to favor pentamer formation, and indeed, mutation of Arg18 into alanine promotes assembly of highly curved particles (cones, spheres, spirals, short capped cylinders). 2011 Nature Introduction HIV R18A 91 109 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Another example of the exclusion mechanism is the multi-drug resistant (MDR) HIV-1 RT known as Q151M complex (Q151Mc). 2011 PloS one Introduction HIV Q151M 95 100 RT 83 85 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Biochemical studies with K65R RT have demonstrated that this enzyme decreases the incorporation rate of these NRTIs. 2011 PloS one Introduction HIV K65R 25 29 NRTI;RT 110;30 115;32 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Here we report the identification of unique HIV clinical isolates that have acquired the K70Q mutation in the background of Q151Mc during TFV-DF-containing therapy. 2011 PloS one Introduction HIV K70Q 89 93 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Increased excision of NRTIs is imparted by Excision Enhancement Mutations, typically M41L, D67N, K70R, T215Y/F, L210W, and K219E/Q (also known as Thymidine Associated Mutations, or TAMs). 2011 PloS one Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 91;123;123;97;112;85;103;103 95;130;130;101;117;89;110;110 NRTI 22 27 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. K65R is another mutation near the polymerase active site that confers NRTI resistance through the exclusion mechanism. 2011 PloS one Introduction HIV K65R 0 4 Pol;NRTI 34;70 44;74 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Q151M by itself causes intermediate- to high-level resistance to zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), and low level resistance to abacavir (ABC) without reducing viral fitness. 2011 PloS one Introduction HIV Q151M 0 5 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Specifically, K65R RT has reduced susceptibility to the acyclic nucleotide analog, TFV and other NRTIs, including ddI, ddC, ABC, FTC and 3TC. 2011 PloS one Introduction HIV K65R 14 18 NRTI;RT 97;19 102;21 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. The crystal structure of K65R RT in complex with DNA and TFV diphosphate (TFV-DP) revealed that R65 forms a molecular platform with the conserved residue R72, and the platform enhances the ability of K65R RT to discriminate NRTIs from dNTPs. 2011 PloS one Introduction HIV K65R;K65R 25;200 29;204 NRTI;RT;RT 224;30;205 229;32;207 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. This mechanism is exemplified by the resistance of the M184V RT mutant to lamivudine (3TC) and emtricitabine (FTC) due to steric clash between the beta-branched Val or Ile at position 184 and the oxathiolane ring of the inhibitors. 2011 PloS one Introduction HIV M184V 55 60 RT 61 63 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. This RT contains the Q151M mutation together with a cluster of four additional mutations (A62V/V75I/F77L/F116Y). 2011 PloS one Introduction HIV A62V;F116Y;F77L;V75I;Q151M 90;105;100;95;21 94;110;104;99;26 RT 5 7 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. While the K65R mutation appeared in several patients treated for more than 18 months with TFV-DF, no patient developed multi-NRTI resistance through appearance of Q151Mc. 2011 PloS one Introduction HIV K65R 10 14 NRTI 125 129 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Additionally, virion-associated RT containing K65R+L74I mutations showed increased processivity in a single round of reverse transcription in comparison to K65R+L74V. 2011 Virology journal Introduction HIV K65R;K65R;L74I;L74V 46;156;51;161 50;160;55;165 RT;RT 117;32 138;34 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Analysis of database (Monogram Biosciences, South San Francisco, CA) have shown that thymidine analogue mutations (TAMs) and M184V are the most common (>25%) followed by L74V/I (11%) and K65R (3.3%) mutations during clinical trials. 2011 Virology journal Introduction HIV K65R;L74I;L74V;M184V 187;170;170;125 191;176;176;130 Capsid 65 67 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Interesting observation regarding the absence of selection of K65R and L74V in the same virus by Bazmi et al. 2011 Virology journal Introduction HIV K65R;L74V 62;71 66;75 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Interestingly, prevalence of these mutations in relation to M184V is strikingly low. 2011 Virology journal Introduction HIV M184V 60 65 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Reverse transcriptase (RT) mutations K65R and L74V/I are selected by several antiretroviral drugs and play important roles in drug susceptibility and/or maintenance of viral load during treatment of HIV-1-infected individuals. 2011 Virology journal Introduction HIV K65R;L74I;L74V 37;46;46 41;52;52 RT;RT 0;23 21;25 HIV infections 199 213 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Similar to K65R+L74V, K65R+L74I is also rarely observed in the absence of other mutations. 2011 Virology journal Introduction HIV K65R;K65R;L74I;L74V 11;22;27;16 15;26;31;20 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The selection of K65R and L74V on the same genome is extremely rare. 2011 Virology journal Introduction HIV K65R;L74V 17;26 21;30 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. This study showed that K65R and L74V were selected during passaging of HIV-1 LAI in the presence of DXG albeit in different viral genome. 2011 Virology journal Introduction HIV K65R;L74V 23;32 27;36 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. To delineate the differences between valine and isoleucine changes at codon 74 in the background of K65R, we created site directed mutants and performed replication kinetics assays in PBM cells and MT-2 cells, and in vitro RT processivity assays. 2011 Virology journal Introduction HIV K65R 100 104 RT 223 225 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We hypothesized that L74I in combination with K65R will have a more profound effect on RT resulting in a highly crippled virus. 2011 Virology journal Introduction HIV K65R;L74I 46;21 50;25 RT 87 89 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We show here that in contrast to our hypothesis, the L74I change leads to a replication competent virus in the background of K65R. 2011 Virology journal Introduction HIV K65R;L74I 125;53 129;57 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We subsequently demonstrated that mutations K65R and L74V are mutually exclusive and a R K reversion occurs at RT codon 65 during replication of virus in peripheral blood mononuclear (PBM) cells in the absence of drugs. 2011 Virology journal Introduction HIV K65R;L74V 44;53 48;57 RT 111 113 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Using this virus as a model system, in this study, we have compared the pathogenicity of WT and V38E mutant in the humanized mice and find that while both viruses replicate to similar levels and induce immune activation, V38E mutant is compromised in its ability to induce a progressive CD4 T cell loss consequent to its failure to induce bystander apoptosis. 2011 Virology journal Introduction HIV V38E;V38E 96;221 100;225 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. We have previously characterized a HIV variant with a single amino acid mutation in the gp41 (V38E) that exhibited deficiency in cell-to-cell fusion activity and apoptosis induction in vitro as well as increased Enfuvirtide resistance. 2011 Virology journal Introduction HIV V38E 94 98 gp41 88 92 21276267 Interplay between HIV entry and transportin-SR2 dependency. An HIV-1 strain with a mutation in CA (N74D) was capable of escaping this phenotype. 2011 Retrovirology Introduction HIV N74D 39 43 Capsid 35 37 21276267 Interplay between HIV entry and transportin-SR2 dependency. To our surprise, the phenotype of the N74D CA mutant virus appeared to be dependent on the viral entry route. 2011 Retrovirology Introduction HIV N74D 38 42 Capsid 43 45 21276267 Interplay between HIV entry and transportin-SR2 dependency. We compared wild type and VSV-G pseudotyped viral vectors and studied the N74D CA mutant which was reported to be independent of TRN-SR2. 2011 Retrovirology Introduction HIV N74D 74 78 Capsid 79 81 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. In contrast, MK-2048 and L-841,411 efficiently produced the ISD complex with N155H. 2011 Journal of molecular biology Introduction HIV N155H 77 82 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. RAL-resistant IN mutant N155H formed the ISD complex at ~25% level of wild type (wt) IN produced in the presence of RAL. 2011 Journal of molecular biology Introduction HIV N155H 24 29 IN;IN 14;85 16;87 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Mixtures of wild-type and variants T215Y in RT, L10F, I54V and V82A in PR appeared 6 months after the first mixture at position 184 was detected. 2011 PloS one Introduction HIV I54V;L10F;T215Y;V82A 54;48;35;63 58;52;40;67 PR;RT 71;44 73;46 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The authors reported a faster rate of reversion for primary resistance mutations (K70R, M184I/V, T215Y/F in RT, and D30N, M46I/L, V82A, L90M in PR) compared to secondary mutations (M41L, D67N, T69D/N, L210W, K219Q/E in RT and L10I/V, L63P, A71V/T, V77I in PR). 2011 PloS one Introduction HIV A71T;A71V;D30N;D67N;K219E;K219Q;K70R;L10I;L10V;L210W;L63P;L90M;M184I;M184V;M41L;M46I;M46L;T215F;T215Y;T69D;T69N;V77I;V82A 240;240;116;187;208;208;82;226;226;201;234;136;88;88;181;122;122;97;97;193;193;248;130 246;246;120;191;215;215;86;232;232;206;238;140;95;95;185;128;128;104;104;199;199;252;134 PR;PR;RT;RT 144;256;108;219 146;258;110;221 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? As example, M184V/I, the most prevalent NRTI-mutations selected under 3TC or FTC in the reverse transcriptase, do for instance revert partially the effect of thymidine-analogue mutation- (TAM) on resistance. 2011 AIDS research and therapy Introduction HIV M184I;M184V 12;12 19;19 RT;NRTI 88;40 109;44 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? K65R and L74V are further mutations which can confer hypersusceptibility or resensitization to AZT. 2011 AIDS research and therapy Introduction HIV L74V;K65R 9;0 13;4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Thus, for deep salvage therapy situations in patients with strongly limited therapy options, it might be of advantage to maintain these drugs in treatment regimens to preserve L76V in the current replicating virus in combination with a "resensitized" drug ATV or SQV. 2011 AIDS research and therapy Introduction HIV L76V 176 180 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. A second possible site of protein-protein activation includes the highly conserved Nef residue R106 at the N-terminal end of alpha-helix 2 The R106A mutation severely reduces Nef-induced PAK2 activation, but like the AQVALR mutation, it is not specific for PAK2 activation. 2011 Journal of neuroimmune pharmacology Introduction HIV R106A 143 148 Nef;Nef 83;175 86;178 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Demonstration of Nef, AP-2, and the cytoplasmic tail of CD4 in a tripartite complex required a Y4H system. 2011 Journal of neuroimmune pharmacology Introduction HIV Y4H 95 98 Nef 17 20 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Partial reductions in the process are observed for Nefs with P72A/P75A and E62A/E63A/E64A/E65A mutations. 2011 Journal of neuroimmune pharmacology Introduction HIV E62A;E63A;E64A;E65A;P72A;P75A 75;80;85;90;61;66 79;84;89;94;65;70 Nef 51 55 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. These assumptions made it possible to design the appropriate tests, with Y4H for Nef-CD4 and MHCIct-NefLLAA for Nef-MHCI, to demonstrate ternary interactions. 2011 Journal of neuroimmune pharmacology Introduction HIV Y4H 73 76 Nef;Nef 81;112 84;115 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Unlike the mutations AQVALR and R106A, this third class of mutations is highly specific for PAK2 activation. 2011 Journal of neuroimmune pharmacology Introduction HIV R106A 32 37 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. For example, connection domain mutation N348I has been observed to emerge early with failure of zidovudine(ZDV)/lamivudine(3TC)/nevirapine(NVP) and reduces sensitivity to ZDV, didanosine, NVP, efavirenz (EFV), delavirdine, tenofovir and etravirine either as a single mutation or in the context of polymerase domain resistance mutations. 2011 Journal of acquired immune deficiency syndromes (1999) Introduction HIV N348I 40 45 Pol 297 307 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. Other connection domain mutations, including G333D/E, G335C/D, A360I/V, A365I and A376S have been shown to decrease ZDV susceptibility in the presence of thymidine analog mutations (TAMs), and mutation T369I increases resistance to NNRTI in the presence of NNRTI-resistance mutations. 2011 Journal of acquired immune deficiency syndromes (1999) Introduction HIV A360I;A360V;A365I;A376S;G333D;G333E;G335C;G335D;T369I 63;63;72;82;45;45;54;54;202 70;70;77;87;52;52;61;61;207 NNRTI;NNRTI 232;257 237;262 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Compared to its parent, CC1/85, the CC101.6 isolate contains an amino acid change in V3, H308P, that renders it up to 4-fold less sensitive to such small molecules as AD101 and VCV. 2011 Virology Introduction HIV H308P 89 94 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Mutagenesis studies on clones derived from the D101.12 isolate show that strong resistance to VCV can be conferred when the H308P sequence change in V3 is combined with specific changes in the N-terminal region of gp41, including, but not limited to, the FP. 2011 Virology Introduction HIV H308P 124 129 gp41 214 218 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The resistance phenotype of isolate CC101.19, for example, has been attributed to four substitutions in V3 (K305R, H308P, A316V and G321E), with the proline at position 308 being the most critical determinant of resistance. 2011 Virology Introduction HIV A316V;G321E;H308P;K305R 122;132;115;108 127;137;120;113 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. We show here that two different gp41 lineages co-exist in the D101.12 isolate and clones derived from it, together with at least the H308P substitution in V3. 2011 Virology Introduction HIV H308P 133 138 gp41 32 36 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Additionally, the effect of the mutation on the autocatalytic processing of the precursor, which is required for onset of the catalytic activity characteristic of the mature, dimeric enzyme, was assessed in vitro, and the effect of a second mutation, M46I, was examined in the precursor containing both mutations. 2011 Biochemistry Introduction HIV M46I 251 255 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Instead, mutants containing L76V exhibit increased susceptibility to these drugs. 2011 Biochemistry Introduction HIV L76V 28 32 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. L76V, generally accompanied by other mutations, is considered a major mutation providing 2-6-fold decreased susceptibility to darunavir (DRV), fosamprenavir, indinavir (IDV), and lopinavir (LPV). 2011 Biochemistry Introduction HIV L76V 0 4 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Presence of L76V as a single mutation was shown to hamper viral replication severely. 2011 Biochemistry Introduction HIV L76V 12 16 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The L76V mutation has become more prevalent in datasets of HIV-1 mutants observed in patients. 2011 Biochemistry Introduction HIV L76V 4 8 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. We constructed PR with the single mutation of L76V in order to investigate its effect on the structure, stability and activity of the enzyme. 2011 Biochemistry Introduction HIV L76V 46 50 PR 15 17 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. For example, a single amino acid change in human TRIM5alpha (TRIM5alphahu), R332P, renders the protein capable of binding the HIV-1 capsid, causing it to behave like rhesus TRIM5alpha (TRIM5alpharh) with regard to HIV-1 restriction. 2011 PLoS pathogens Introduction HIV R332P 76 81 Capsid 132 138 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. Triple-drug regimens containing lamivudine (3TC) and NNRTI commonly fail with M184V plus one or more NNRTI-associated mutations and subsequent accumulation of thymidine analogue mutations (TAM) and/or, more infrequently, one or more members of the Q151M multinucleoside resistance complex. 2011 International health Introduction HIV M184V;Q151M 78;248 83;253 NNRTI;NNRTI 53;101 58;106 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Combination of Gag and Env mutants Y164A/R515A was the most potent at suppressing WT HIV. 2011 Virology Introduction HIV R515A;Y164A 41;35 46;40 Env;Gag 23;15 26;18 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Elucidation of the mechanism of inhibition demonstrated that Y164A/R515A acted at multiple steps of the virus life cycle, including assembly and release as well as entry and post-entry of the progeny virions. 2011 Virology Introduction HIV R515A;Y164A 67;61 72;66 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. In the gag gene we used the MA mutant 1GA, and CA mutants Q155N and Y164A because of their ability to retain interaction with WT Gag but not be rescued to produce virions, while for the env gene we selected the cleavage-defective (R515A) or fusion-defective Env mutant V513E (also known as the 41.2 mutant) and a combination thereof. 2011 Virology Introduction HIV Q155N;R515A;V513E;Y164A 58;231;269;68 63;236;274;73 Env;Env;Gag;Gag;Matrix;Capsid 186;258;7;129;28;47 189;261;10;132;30;49 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Interestingly, the inhibition mediated by R515A was partially attributed to the Env cytoplasmic tail. 2011 Virology Introduction HIV R515A 42 47 Env 80 83 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. However, few data are available on the evolution and genetic linkage of C-terminal mutations in the context of Q151M MDR complex, especially in non-B subtypes. 2011 Retrovirology Introduction HIV Q151M 111 116 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. In this study, we performed a detailed analysis of sequential samples collected from a patient in the CHAP2 cohort study who had developed resistance via the Q151M pathway to dissect the intrapatient viral population dynamics in the context of full-length RT. 2011 Retrovirology Introduction HIV Q151M 158 163 RT 256 258 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. It is believed that the Q151M MDR complex occurs infrequently because the Q151 to M mutation requires a 2-bp change (CAG to ATG), and the two possible intermediate changes of Q151L (CAG to CTG) and Q151K (CAG to AAG) significantly reduce viral replication capacity in vitro and are seldom observed in vivo . 2011 Retrovirology Introduction HIV Q151K;Q151L;Q151M 198;175;24 203;180;29 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. N348I confers resistance by reducing RNase H activity which allows more time for the excision or dissociation of the RT inhibitors. 2011 Retrovirology Introduction HIV N348I 0 5 RT 117 119 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Some of these mutations, such as N348I in the connection subdomain, have been reported to have a prevalence of 10-20% in treatment-experienced individuals. 2011 Retrovirology Introduction HIV N348I 33 38 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The N348I mutation is associated with M184V and TAMs, and increases resistance to NRTIs such as AZT, as well as the NNRTI NVP. 2011 Retrovirology Introduction HIV M184V;N348I 38;4 43;9 NNRTI;NRTI 116;82 121;87 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The Q151M complex has been identified in up to 19% of patients failing therapy containing stavudine (d4T) as part of ART rollout in the developing world, particularly where treatment is given without virological monitoring, thus allowing long term viraemia whilst on first-line therapy. 2011 Retrovirology Introduction HIV Q151M 4 9 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The Q151M MDR complex is composed of the Q151M mutation, which is normally the first to appear, followed by at least two of the following four mutations: A62V, V75I, F77L and F116Y. 2011 Retrovirology Introduction HIV A62V;F116Y;F77L;Q151M;Q151M;V75I 154;175;166;4;41;160 158;180;170;9;46;164 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The Q151M MDR complex was initially described to develop during long-term NRTI-containing combination therapy or NRTI therapy with zidovudine (AZT) and/or didanosine (ddI); however, it is now rarely observed in resource-rich countries, where more potent cART is used. 2011 Retrovirology Introduction HIV Q151M 4 9 NRTI;NRTI 74;113 78;117 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The Q151M MDR is important because it has been shown to confer resistance to almost all NRTIs with the exception of TDF. 2011 Retrovirology Introduction HIV Q151M 4 9 NRTI 88 93 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The replicative capacity of a Q151L-containing virus was shown to improve in the presence of S68G and M230I mutations suggesting that compensatory mutations could favour the emergence of the Q151M MDR complex. 2011 Retrovirology Introduction HIV M230I;Q151L;Q151M;S68G 102;30;191;93 107;35;196;97 21569500 Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. Tat RSS activity is genetically separable from Tat transcriptional activity by K51A substitution in the double-stranded RNA binding domain. 2011 Retrovirology Introduction HIV K51A 79 83 Tat;Tat 0;47 3;50 21569500 Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. The delay in HIV-1 replication by Tat K51A substitution can be complemented by TBSV P19 and rice hoja blanca virus non-structural protein 3 (NS3). 2011 Retrovirology Introduction HIV K51A 38 42 Tat 34 37 21569500 Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. Translation of virion structural protein is exacerbated by K51A substitution in the Tat RNA binding domain (HIV-1NL4-3RSS). 2011 Retrovirology Introduction HIV K51A 59 63 Tat 84 87 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. examined viral fitness in 8 clinical isolates compared with HIVNL4-3, however none of these isolates contained the D30N mutation. 2010 The open medical informatics journal Introduction HIV D30N 115 119 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The D30N has been identified to biochemically alter viral protease activity in heterologous cleavage studies. 2010 The open medical informatics journal Introduction HIV D30N 4 8 PR 58 66 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The D30N mutation in the protease (PR) gene involves a GAT to AAT mutation that is well-characterized and specific to the protease inhibitor nelfinavir (NFV). 2010 The open medical informatics journal Introduction HIV D30N 4 8 PR;PR;PR 25;122;35 33;130;37 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The M184V mutation in the reverse transcriptase (RT) gene, which causes primary resistance to lamuvidine (3TC), has been extensively studied and is common in treated patients. 2010 The open medical informatics journal Introduction HIV M184V 4 9 RT;RT 26;49 47;51 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Viral isolates with the M184V mutation in RT have lower RC than viral isolates without the mutation. 2010 The open medical informatics journal Introduction HIV M184V 24 29 RT 42 44 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. In contrast to adults where K103N predominates, the predominant mutation among infants is Y181C. 2011 AIDS (London, England) Introduction HIV K103N;Y181C 28;90 33;95 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. We ascertained resistance using both standard genotyping and more sensitive AS-PCR methods for the Y181C and K103N mutations. 2011 AIDS (London, England) Introduction HIV K103N;Y181C 109;99 114;104 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. A single nucleotide (nt) mutation is required for both subtype B (AAA AGA) (Figure 1A) and subtype C (AAG AGG) (Figure 1B) viruses to develop the K65R mutation. 2011 PloS one Introduction HIV K65R 146 150 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Another recent report suggests that high-fidelity enzymes used in DNA amplification reactions as well as HIV-1 RT can also erroneously produce K65R. 2011 PloS one Introduction HIV K65R 143 147 RT 111 113 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. However, these data cannot confirm that the transcripts produced at the pause site contain K65R or some other mutational byproduct, or that the mutations produced may generate viable virus. 2011 PloS one Introduction HIV K65R 91 95 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In addition, numerous clinical studies have also demonstrated higher rates of K65R development ranging between 9 and 30% in subtype C-infected individuals who failed treatment. 2011 PloS one Introduction HIV K65R 78 82 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In contrast, thymidine analogue mutations (TAMs) do not have the discriminatory properties of K65R and, as a result, are mutually exclusive with the latter and are rarely found on the same viral genome. 2011 PloS one Introduction HIV K65R 94 98 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. K65R is also responsible for reductions in: viral fitness, natural dNTP incorporation, N(t)RTI incorporation, and N(t)RTI excision. 2011 PloS one Introduction HIV K65R 0 4 NRTI;NRTI 87;114 94;121 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. K65R-associated treatment failures are uncommon and usually develop at rates between 0 and 3%. 2011 PloS one Introduction HIV K65R 0 4 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The current manuscript extends our previous results by providing an additional mechanistic basis for the hyper-presence of K65R in subtype C HIV-1. 2011 PloS one Introduction HIV K65R 123 127 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The data showed that a strong pause site was present at the exact nt position responsible for K65R development during positive double-stranded DNA ((+)dsDNA) synthesis from the negative single-stranded DNA ((-)ssDNA) intermediate template. 2011 PloS one Introduction HIV K65R 94 98 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The K65R mutation in HIV-1 RT is responsible for varying levels of reduced phenotypic susceptibility to most approved nucleotide and nucleoside reverse transcriptase inhibitors (N(t)RTIs). 2011 PloS one Introduction HIV K65R 4 8 NRTI;NRTI;RT 133;178;27 165;186;29 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. These data provide mechanistic insight into K65R development in subtype C and are important in understanding the development of drug resistance in subtype C-infected patients. 2011 PloS one Introduction HIV K65R 44 48 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. To explore this discrepancy, biochemical analysis of the RT enzymes derived from both subtypes were performed and showed that they are very similar; the subtype origin of RT cannot explain the discrepancies observed with respect to K65R development. 2011 PloS one Introduction HIV K65R 232 236 RT;RT 57;171 59;173 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. To investigate whether these polymorphisms in the viral templates might be involved in the preferential acquisition of K65R, we studied DNA synthesis from viral RNA and DNA templates derived from either subtype B or C HIV-1. 2011 PloS one Introduction HIV K65R 119 123 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. We also evaluated the products of such dislocation that can yield both frameshift mutants in the pre-realignment phase and full-length K65R-containing transcripts in the post-realignment phase. 2011 PloS one Introduction HIV K65R 135 139 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. We now show that the production of transcripts containing the mutagenic G nt at the middle position of codon 65 by HIV-1 RT is facilitated on subtype C templates and that template site-specific dislocation is the underlying mechanism responsible for the higher rates of K65R development. 2011 PloS one Introduction HIV K65R 270 274 RT 121 123 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. We recently showed that subtype C HIV-1 developed the K65R mutation more readily than subtype B viruses in tissue culture. 2011 PloS one Introduction HIV K65R 54 58 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. When two silent nt polymorphisms at codons 64 and 65 of the subtype C RT sequence were introduced into a wild-type NL4-3 virus of subtype B origin in cell culture, the resultant virus behaved like a subtype C virus in terms of K65R development. 2011 PloS one Introduction HIV K65R 227 231 RT 70 72 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. The pre-existence of resistance mutations can significantly diminish effectiveness of subsequent ARV therapy; for example, transmitted K103N mutations are associated with increased regimen failure and poorer outcomes on non-nucleoside reverse transcriptase inhibitors (NNRTIs). 2011 PloS one Introduction HIV K103N 135 140 NNRTI;NNRTI 220;269 256;275 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The lysine (K) to asparagine (N) mutation at codon 103 (K103N) in particular confers great resistance to efavirenz. 2011 PloS one Introduction HIV K103N 56 61 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We also investigated whether the pharmacokinetics variability of efavirenz influenced the emergence of K103N mutants and analyzed the impact of emergent K103N mutants on the subsequent virological response to combined antiretroviral therapy (cART). 2011 PloS one Introduction HIV K103N;K103N 103;153 108;158 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We have now evaluated the performances of allele-specific real-time PCR and ultra-deep pyrosequencing for detecting the emergence of minor virus populations harboring the K103N mutation in patients in the intermittent arm receiving efavirenz. 2011 PloS one Introduction HIV K103N 171 176 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. The K103N and M184V mutations were chosen, because they are commonly transmitted drug resistance mutations. 2011 PloS one Introduction HIV K103N;M184V 4;14 9;19 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Some of these mutations, such as the S138A substitution, have been suggested to confer some resistance per se , but others do not or only modestly impact the level of resistance. 2011 PloS one Introduction HIV S138A 37 42 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. found K103N as the most common resistance mutation in patients failing regimens containing tenofovir, FTC and efavirenz or zidovudine, 3TC and EFV. 2011 PloS one Introduction HIV K103N 6 11 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. K103N and Y188L confer high-level resistance to NVP and EFV, while Y181C/I/V and G190A mainly reduce susceptibility to NVP. 2011 PloS one Introduction HIV G190A;Y181C;Y181I;Y181V;Y188L;K103N 81;67;67;67;10;0 86;76;76;76;15;5 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. M184V and K103N/Y181C were seen in >10% of patients failing antiretroviral therapy in British Columbia, Canada during 1996 to 2003. 2011 PloS one Introduction HIV K103N;Y181C;M184V 10;16;0 15;21;5 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. The presence of the M184V mutation results in >100-fold decreased susceptibility to both drugs. 2011 PloS one Introduction HIV M184V 20 25 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. A conservative substitution of Tyr183 to Phe183 resulted in 70% loss of polymerase activity and a significant increase in the fidelity of DNA synthesis. 2011 Biochemistry Introduction HIV Y183F 32 48 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Here we investigated three patients for whom conventional viral population genotyping identified an N155H to Q148H pathway switch. 2011 AIDS (London, England) Introduction HIV N155H;Q148H 100;109 105;114 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Specifically, the N155H pathway is commonly replaced by the Q148H/R/K pathway, resulting in reduced susceptibility to RAL and improved viral replication capacity. 2011 AIDS (London, England) Introduction HIV N155H;Q148H;Q148K;Q148R 18;60;60;60 23;69;69;69 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Three codons can mutate to generate primary resistance mutations, which encode Y143R/C/H, Q148H/R/K, and N155H. 2011 AIDS (London, England) Introduction HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 105;90;90;90;79;79;79 110;99;99;99;88;88;88 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. 10 nM EC50 values, against both WT HIV-1 and variants containing the Y181C RT mutation. 2011 Journal of the American Chemical Society Introduction HIV Y181C 69 74 RT 75 77 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. For the Y181C variant, the 1s9e structure was also used as the starting point and the tyrosine was manually modified to cysteine. 2011 Journal of the American Chemical Society Introduction HIV Y181C 8 13 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. However, similar to nevirapine, 1 and 2 show no activity against virus encoding the Tyr181Cys (Y181C) mutation in the reverse transcriptase enzyme. 2011 Journal of the American Chemical Society Introduction HIV Y181C;Y181C 84;95 93;100 RT 118 139 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. Most first-generation NNRTIs including nevirapine and delavirdine do not have useful activity towards Y181C containing variants, while efavirenz, etravirine, and rilpivirine retain 1-10 nM potency. 2011 Journal of the American Chemical Society Introduction HIV Y181C 102 107 NNRTI 22 28 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The expectation has been that the inactivity towards the Y181C variant stems largely from loss of the favorable contact between Tyr181 and the ODMA group. 2011 Journal of the American Chemical Society Introduction HIV Y181C 57 62 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. By comparing these isolates with IN mutants generated by single-site mutagenesis, we demonstrate that G140S/Q148R and N155H are sufficient to confer resistance to RAL, whereas Y143C mutation is not. 2011 Retrovirology Introduction HIV G140S;N155H;Q148R;Y143C 102;118;108;176 107;123;113;181 IN 33 35 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Secondary resistance mutations, such as G140S, which have little or no direct effect on drug susceptibility per se, increase phenotypic resistance or viral fitness. 2011 Retrovirology Introduction HIV G140S 40 45 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The third pathway, involving the Y143R/C mutation, is less frequently observed and was identified after the N155 and Q148 pathways. 2011 Retrovirology Introduction HIV Y143C;Y143R 33;33 40;40 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The virological failure of RAL-based treatment in HIV-1 infection is associated primarily with the initial, independent development of the principal N155H and Q148H/K/R pathways, either alone or together with other resistance mutations. 2011 Retrovirology Introduction HIV N155H;Q148H;Q148K;Q148R 149;159;159;159 154;168;168;168 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. We show also that N155H and Y143C mutations have antagonistic effects. 2011 Retrovirology Introduction HIV N155H;Y143C 18;28 23;33 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. Our experimental data also explain how crystallization conditions, as well as the single amino-acid substitution A182T between the RAV-1 IN CCD and the well-studied RSV-A (strain Schmidt-Ruppin A) IN CCD, can favor either dimeric form during crystal growth. 2011 PloS one Introduction HIV A182T 113 118 IN;IN 137;197 139;199 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. By contrast, there is some discrepancy in the literature in regard to the mechanisms associated with nevirapine resistance: one study has suggested it is due to decreased inhibitor binding, while other studies suggest that it may also be due to the decreased RNase H cleavage phenotype of the N348I HIV-1 RT. 2011 Retrovirology Introduction HIV N348I 293 298 RT 305 307 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Furthermore, N348I can compensate for the antagonism of thymidine analog mutations (TAMs) by the L74V, Y181C or M184V mutations. 2011 Retrovirology Introduction HIV L74V;M184V;N348I;Y181C 97;112;13;103 101;117;18;108 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. In this regard, the N348I mutation in the connection domain of HIV-1 RT has received significant attention in the last 4 years. 2011 Retrovirology Introduction HIV N348I 20 25 RT 69 71 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Previous biochemical studies demonstrated that N348I in HIV-1 RT indirectly increases AZT resistance by decreasing the frequency of secondary ribonuclease H (RNase H) cleavages that significantly reduce the RNA/DNA duplex length of the template/primer (T/P) and diminish the efficiency of AZT-monophosphate (MP) excision. 2011 Retrovirology Introduction HIV N348I 47 52 RT 62 64 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Therefore, it is not evident how N348I in HIV-1 RT impacts the RNase H cleavage of the enzyme or decreases drug susceptibility. 2011 Retrovirology Introduction HIV N348I 33 38 RT 48 50 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Overall, our findings support the use of raltegravir for HIV-2 treatment and demonstrate that the Q148R and N155H changes alone are sufficient for phenotypic resistance to raltegravir in HIV-2. 2011 AIDS (London, England) Introduction HIV N155H;Q148R 108;98 113;103 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. recently reported that Q148R and N155H individually improve the ability of purified HIV-2 integrase to catalyze strand transfer in the presence of raltegravir, whereas the Y143C change alone had no impact on raltegravir sensitivity. 2011 AIDS (London, England) Introduction HIV N155H;Q148R;Y143C 33;23;172 38;28;177 IN 90 99 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Specific amino acid changes that are known to confer raltegravir resistance in HIV-1 have been observed in integrase sequences from raltegravir-treated HIV-2 patients; these commonly include Q148R, N155H and, to a lesser extent, Y143C. 2011 AIDS (London, England) Introduction HIV N155H;Q148R;Y143C 198;191;229 203;196;234 IN 107 116 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. HIV envelope mutations that impact neutralization susceptibility at distal sites had been reported prior to this study and more recently although these amino acid changes typically did not demonstrate the magnitude and/or breadth of the effects caused by the T569A and I675V changes. 2011 Virology Introduction HIV I675V;T569A 269;259 274;264 Env 4 12 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Specifically, two changes in gp41, a T to A at position 569 (T569A) and an I to V change at position 675 (I675V) increased neutralization sensitivity to a variety of NAbs, including those that target gp41 as well as those that recognize distal sites in gp120. 2011 Virology Introduction HIV I675V;I675V;T569A;T569A 106;75;61;37 111;104;66;59 gp120;gp41;gp41 253;29;200 258;33;204 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. The T569A and I675V changes showed similar effects on neutralization sensitivity when introduced into other envelope variants, including variants from different subtypes. 2011 Virology Introduction HIV I675V;T569A 14;4 19;9 Env 108 116 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Other work on CA residues S108, S149, and S178, which have the potential to be phosphorylated, showed that an S149A mutant has low infectivity and is only partially defective in other assays. 2011 Virology Introduction HIV S149A 110 115 Capsid 14 16 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Thus, despite the instability of P147L and S149A cores, these mutants retain an ability to undergo reverse transcription (albeit less efficiently than WT) and can assemble conical cores that resemble those of WT virions. 2011 Virology Introduction HIV P147L;S149A 33;43 38;48 RT 99 120 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Two mutants (P147L and S149A), while poorly infectious, have a novel, attenuated phenotype. 2011 Virology Introduction HIV P147L;S149A 13;23 19;28 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Two mutants (S146A and T148A) behave like WT, whereas three other mutants (Y145A, I150A, and L151A) are noninfectious and exhibit severe defects in core assembly and stability and viral DNA synthesis in infected cells. 2011 Virology Introduction HIV I150A;L151A;S146A;T148A;Y145A 82;93;13;23;75 87;98;19;28;80 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Using a hyperstable capsid mutant, E45A, we further show intact HIV-1 cores released into the cytoplasm after membrane fusion. 2011 Structure (London, England Introduction HIV E45A 35 39 Capsid 20 26 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. With regard to subtype, in subjects infected with HIV-1 subtype B, the thymidine analogue mutations pathway 1 or TAM-1 (including mutations M41L, L210W and T215Y) is probably more frequent than the TAM-2 pathway (including mutations D67N, K70R, T215F and K219E/Q), although systematic studies of these pathways have not been done. 2011 PloS one Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 233;255;255;239;146;140;245;156 237;262;262;243;151;144;250;161 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Overall, the data indicate that mutant Q105N elicits greater CD4bs-specific antibody responses when formulated with the adjuvant Quil A. 2012 Vaccine Introduction HIV Q105N 39 44 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. This report focuses on the head-to-head comparison of the ability of MPL and Quil A to promote CD4bs-specific antibody responses in mice immunized with the engineered mutant Q105N compared to gp120wt. 2012 Vaccine Introduction HIV Q105N 174 179 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. M184I, for example, is a transient 3TC resistant mutation, ultimately resulting in M184V. 2012 Virology Introduction HIV M184V;M184I 83;0 88;5 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The M184I mutation was also found to change the tropism of an HIV-1 vector, preventing it from transducing human macrophages. 2012 Virology Introduction HIV M184I 4 9 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The requirement of a certain volume in the active site of RT for an incoming dNTP would represent unique mechanism of substrate binding; unlike the mutation Q151N, that decreases the dNTP binding through a loss of interaction or M184I, which results in a steric clash with the incoming dNTP. 2012 Virology Introduction HIV M184I;Q151N 229;157 234;162 RT 58 60 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. We have shown that the M184I mutation also alters the binding of RT to dNTPs, raising the Kd to 56muM, which is similar to the Kd value of MuLV RT. 2012 Virology Introduction HIV M184I 23 28 RT;RT 65;144 67;146 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. We observed a similar outcome with Q151N, a non-clinical RT mutation (light blue). 2012 Virology Introduction HIV Q151N 35 40 RT 57 59 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. All studies are in agreement that mutation of Pro-35 with Ala disrupts the interaction of Vpr with CypA, which is consistent with a conformational change in the hydrophobic core. 2011 BMC structural biology Introduction HIV P35A 46 61 Vpr 90 93 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Mutation of Arg-80 with Ala may cause a change in the folded structure of full-length Vpr or, could in theory, alter the structure of a specific novel C-terminal binding region of Vpr to CypA. 2011 BMC structural biology Introduction HIV R80A 12 27 Vpr;Vpr 86;180 89;183 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. reported that mutation of the C-terminal residue Arg-80 with Ala also prevented coimmunoprecipitation of Vpr with CypA. 2011 BMC structural biology Introduction HIV R80A 49 64 Vpr 105 108 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. A71V mutation in the cantilever region is distant from active site, and has a profound effect on the binding of ligand to the active site through H-bond propagation from the site of mutation. 2012 The journal of physical chemistry. B Introduction HIV A71V 0 4 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. As for other approved PIs, several HIV-pr mutants were demonstrated to have drug resistance over the TMC114, like D30N and I50V, whereas L90M is well adapted by the TMC114. 2012 The journal of physical chemistry. B Introduction HIV D30N;I50V;L90M 114;123;137 118;127;141 PI;PR 22;39 25;41 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. As for the other previous studies, the present results also show that the single mutant I50V decreases the binding affinity of I50V-HIV-pr to TMC, resulting in a drug resistance. 2012 The journal of physical chemistry. B Introduction HIV I50V;I50V 88;127 92;131 PR 136 138 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For both the apo and complexed HIV-pr, the analysis indicates many intriguing effects due to double mutant, I50L/A71V. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L 113;108 117;112 PR 35 37 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. However, although both of the residues are present in two critical locations and their effect on a few other PIs were previously discussed, for the double mutation I50L/A71V there is little information regarding its importance in drug resistance mechanism for the TMC114. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L 169;164 173;168 PI 109 112 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In the present study, to facilitate the investigation of drug resistance mechanism and to obtain information about the binding of TMC114 to the WT and mutant HIV-pr, MD simulations have been performed first for three inhibitor-free (apo) WT, I50V and I50L/A71V HIV-proteases as well as the three inhibitor-bound HIV-proteases. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L;I50V 256;251;242 260;255;246 PR;PR;PR 265;316;162 274;325;164 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. It is interesting to note that the double mutant I50L/A71V increases the binding affinity, and as a result of the stronger binding the I50L/A71V may be well adapted by the TMC114. 2012 The journal of physical chemistry. B Introduction HIV A71V;A71V;I50L;I50L 54;140;49;135 58;144;53;139 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. It was found that loss of H-bonds between Asp30 and TMC114 drives the drug resistance in D30N, whereas for I50V it is the increased polar solvation energies for the two residues Asp30' and Val50'. 2012 The journal of physical chemistry. B Introduction HIV D30N;I50V 89;107 93;111 Asp;Asp 42;178 45;181 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Mutation I50L is a signature mutation for atazanavir (ATV) resistance, and has increased susceptibility to other inhibitors with the presence of other primary and secondary resistance mutations. 2012 The journal of physical chemistry. B Introduction HIV I50L 9 13 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Mutation I50V and the double mutation I50L/A71V are considered as two of the most key residue mutations of the HIV-pr drug resistance to inhibitors in clinical use. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L;I50V 43;38;9 47;42;13 PR 115 117 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The average flap tip - active site, flap -flap distances and curling behavior of the TriCa angles suggest a closer movement of flaps in the double mutant as compared to WT and I50V, probably making the active site volume smaller. 2012 The journal of physical chemistry. B Introduction HIV I50V 176 180 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The drug resistance mechanism of such mutants was explored at the molecular level with all-atomistic MD simulation combined with molecular mechanics-Poisson/Boltzmann surface area (MM-PBSA) for the binding energies of TMC114 to D30N and I50V mutants. 2012 The journal of physical chemistry. B Introduction HIV D30N;I50V 228;237 232;241 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The flap curling and opening events in I50L/A71V-HIV-pr are more stable than WT and I50V mutant. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L;I50V 44;39;84 48;43;88 PR 53 55 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The primary objectives for the binding energy calculation are to gain an insight into whether the double mutant I50L/A71V provides drug resistance to TMC114, and then to analyze the detailed interaction mechanism at a molecular level. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L 117;112 121;116 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The resistance of the inhibitor GRL-98065, an analog of TMC114 just aniline group replaced by a 1,3-benzodioxole group, to mutants I50V and V82A was attributed to a higher entropic contribution than in the wild type (WT) HIV-pr, and the reduced van der Waals may be responsible to the drug resistance of I84V to GRL-98065. 2012 The journal of physical chemistry. B Introduction HIV I50V;I84V;V82A 131;304;140 135;308;144 PR 225 227 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. There is a flip-flop of the interaction between the catalytic Asp25 OD1/OD2 atoms and O18 of TMC114, which may be due to the effect of the mutation A71V from the double mutant, where the change from Ala to Val modifies the H-bonding pattern between the four anti-parallel beta-sheets connecting Asp25 site to Val71. 2012 The journal of physical chemistry. B Introduction HIV A71V 148 152 Asp;Asp 62;295 65;298 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Thus, the double mutation (I50L/A71V) effect of the two important residues Ile50 and Ala71 on HIV-pr structure and its difference from the single mutation (I50V) influence, prompt us to investigate the changes in binding affinity of the inhibitor TMC114 to the protease. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L;I50V 32;27;156 36;31;160 PR;PR 261;98 269;100 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. With isothermal titration calorimetry, Yanchunas et al showed that protease enzymes containing I50L/A71V exhibit increased binding to seven inhibitors relative to wild-type HIV-pr, being parallel to the increased susceptibility of recombinant viruses with this mutation. 2012 The journal of physical chemistry. B Introduction HIV A71V;I50L 100;95 104;99 PR;PR 67;177 75;179 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. A large proportion of these patients harboured mutations associated with cross-resistance to most NRTIs (K65R [19%], Q151M [19%] and/or thymidine analogue mutations (TAMs) [56%]), limiting the potential future use of fully susceptible NRTIs. 2012 Antiviral therapy Introduction HIV K65R;Q151M 105;117 110;122 NRTI;NRTI 98;235 103;240 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Furthermore, K65R has been observed in a high frequency, which is linked to nucleotide changes in HIV-1 subtype C. 2012 Antiviral therapy Introduction HIV K65R 13 17 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. In this setting, consistent resistance data from ART centres reflect a maximum of 39% complex drug resistance patterns (defined as the presence of either K65R and/or Q151M and/or 2 or more thymidine analogue mutations). 2012 Antiviral therapy Introduction HIV K65R;Q151M 154;166 158;171 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The high level of NRTI resistance, due to mutations K65R, Q151M and TAMs would weaken second-line regimens, containing a boosted PI as the only active ARV. 2012 Antiviral therapy Introduction HIV K65R;Q151M 52;58 56;63 NRTI;PI 18;129 22;131 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Despite virological failure, specific mutations (the cluster V38A+N140I) have been associated with an increase in CD4+ T cell counts. 2012 Retrovirology Introduction HIV N140I;V38A 66;61 71;65 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. However, the mutation V38A in the context of a 140N or 140T change did not alter Env functions, underscoring the importance of the Env genetic background in the modulation of the cytopathic effects of the HIV-1 Env glycoproteins. 2012 Retrovirology Introduction HIV V38A 22 26 Env;Env;Env 81;131;211 84;134;214 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Our results indicate that the primary gp41 Env proteins, with both V38A and N140I changes, induced lower levels of single-cell death and depletion of CD4+ T cells, although they retained cell-to-cell fusion activity. 2012 Retrovirology Introduction HIV N140I;V38A 76;67 81;71 gp41;Env 38;43 42;46 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. The most common drug resistance mutation pattern by standard HIV genotyping in patients experiencing virologic failure on an initial regimen of Tenofovir/Emtricitabine (TDF/FTC) plus a ritonavir boosted protease inhibitor (PI/r) is a solitary reverse transcriptase (RT) M184V mutation or no resistance mutations. 2012 PloS one Introduction HIV M184V 268 275 RT;PR;PI;RT 243;203;223;266 264;211;225;268 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A second pattern includes D67N, K70R, T215F and K219Q/E (TAM-2 pathway). 2012 PloS one Introduction HIV D67N;K219E;K219Q;K70R;T215F 26;48;48;32;38 30;55;55;36;43 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Consistent with this observation, mechanistic analyses suggest that this mutation may compensate for the antagonism of TAMs by M184V/I and Y181C. 2012 PloS one Introduction HIV M184I;M184V;Y181C 127;127;139 134;134;144 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. For example, the G333D/E, G335C, N348I, A360V/I, T369V and A371V mutations have all be shown to augment AZT resistance alone or in combination with TAMs. 2012 PloS one Introduction HIV A360I;A360V;A371V;G333D;G333E;G335C;N348I;T369V 40;40;59;17;17;26;33;49 47;47;64;24;24;31;38;54 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. For example, Yap et al reported that the N348I mutation is highly associated with TAMs, the lamivudine mutation M184V/I, and the non-nucleoside inhibitor resistance mutations K103N and Y181C/I. 2012 PloS one Introduction HIV K103N;M184I;M184V;N348I;Y181C;Y181I 175;112;112;41;185;185 180;119;119;46;192;192 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Resistance was conferred by mutations in the polymerase domain of RT that included D67N, K70R, T215Y/F and K219Q. 2012 PloS one Introduction HIV D67N;K219Q;K70R;T215F;T215Y 83;107;89;95;95 87;112;93;102;102 Pol;RT 45;66 55;68 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Subsequently, two additional AZT resistance mutations were identified: M41L and L210W. 2012 PloS one Introduction HIV L210W;M41L 80;71 85;75 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected participants selects the A371V, Q509L or other mutations in the connection or RNase H domains of RT. 2012 PloS one Introduction HIV A371V;Q509L 114;121 119;126 RT 186 188 HIV infections 74 88 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The most common combination of mutations selected includes M41L, L210W and T215Y and excludes K70R (TAM-1 pathway). 2012 PloS one Introduction HIV K70R;L210W;M41L;T215Y 94;65;59;75 98;70;63;80 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Two novel mutations - A371V in the connection domain and Q509L in the RNase H domain - were selected in combination with D67N, K70R and T215F that together conferred greater than 100-fold AZT resistance. 2012 PloS one Introduction HIV A371V;D67N;K70R;Q509L;T215F 22;121;127;57;136 27;125;131;62;141 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. For this purpose, we developed, evaluated and applied highly sensitive allele-specific PCR (ASPCR) assays enabling the detection and quantification of three key mutations for AZT resistance (K70R, T215Y and T215F), the two most common NVP-associated resistance mutations (K103N and Y181C) and the most frequent 3TC-selected mutation M184V in the pol open reading frame with a detection limit of <1%. 2012 PloS one Introduction HIV K103N;K70R;M184V;T215F;T215Y;Y181C 272;191;333;207;197;282 278;195;338;212;202;287 Pol 346 349 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. However, N88D is common in association with D30N, which exerts a synergistic effect on resistance to NFV, and the double mutant shows 260-fold increased Ki value for NFV compared to wild-type. 2012 Journal of medicinal chemistry Introduction HIV D30N;N88D 44;9 48;13 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Lastly, mutation of N88D alone is associated primarily with resistance to nelfinavir (NFV). 2012 Journal of medicinal chemistry Introduction HIV N88D 20 24 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Mutations of V82A/T/F/S/L are very common in PI resistance and show reduced susceptibility to all the clinical PIs except DRV. 2012 Journal of medicinal chemistry Introduction HIV V82A;V82F;V82L;V82S;V82T 13;13;13;13;13 25;25;25;25;25 PI;PI 45;111 47;114 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Similarly, L76V mutation shows decreased susceptibility for APV, DRV and LPV. 2012 Journal of medicinal chemistry Introduction HIV L76V 11 15 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Two of the mutations, I47V and V82A, are located inside the inhibitor binding site (Figure 1B). 2012 Journal of medicinal chemistry Introduction HIV I47V;V82A 22;31 26;35 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. (2011) showed that an average of 34% of South African children under the age of 24 months had developed non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, in particular the Y181C mutation, when they were previously exposed to single dose nevirapine (sdNVP). 2012 PloS one Introduction HIV Y181C 189 194 NNRTI;NNRTI 104;152 140;157 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In the present study, we identified second-site substitutions in CA that restore the ability of HIV-1 mutants containing unstable (P38A) or hyperstable (E45A) capsids to replicate in T cells. 2012 Retrovirology Introduction HIV E45A;P38A 153;131 157;135 Capsid;Capsid 159;65 166;67 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. One of the mutants, Q63A/Q67A, resulting in unstable capsids in vitro, was competent for reverse transcription but impaired for nuclear import. 2012 Retrovirology Introduction HIV Q63A;Q67A 20;25 24;29 RT;Capsid 89;53 110;60 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Four V3 substitutions (K305R, H308P, A316V and G321E) were, for example, responsible for the resistant phenotype of isolate CC101.19 when the CCR5-using virus CC1/85 was cultured with the small molecule CCR5 inhibitor AD101. 2012 Virology Introduction HIV A316V;G321E;H308P;K305R 37;47;30;23 42;52;35;28 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Here, we have studied the pathway including the F519I change. 2012 Virology Introduction HIV F519I 48 53 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Here, we report that the G516V change is critical to VCV resistance, although it must be accompanied by either M518V or F519I to have a substantial impact. 2012 Virology Introduction HIV F519I;G516V;M518V 120;25;111 125;30;116 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. However, the FP changes were then accompanied by a substitution in the inner domain of gp120, T244A, that is part of a beta-sandwich structure involved in gp41 interactions. 2012 Virology Introduction HIV T244A 94 99 gp120;gp41 87;155 92;159 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The D101.12 escape mutants contained at least one substitution in V3 (H308P) as well as either of the following combinations of substitutions within and immediately downstream of the gp41 fusion peptide (FP): G514V+V535M or M518V+F519L+V535M. 2012 Virology Introduction HIV F519L;G514V;H308P;M518V;V535M;V535M 230;209;70;224;215;236 235;214;75;229;220;241 gp41 183 187 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The emergence of the T244A change counters the VCV-resistance phenotype created by the FP substitutions. 2012 Virology Introduction HIV T244A 21 26 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The phenylalanine (F) residue at position 519 can change either to isoleucine (I) or to leucine (L) depending on the resistance pathway. 2012 Virology Introduction HIV F519F 0 48 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. We have also described a VCV escape pathway for viruses from the D1/85.16 lineage that involved no V3 changes; instead, resistance mapped to three conservative substitutions in the FP: G516V, M518V and F519I. 2012 Virology Introduction HIV F519I;G516V;M518V 202;185;192 207;190;197 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. H221Y was recently found as an NNRTIs mutation which confers resistance to NVP. 2012 AIDS research and treatment Introduction HIV H221Y;H221Y 2;0 6;5 NNRTI 31 37 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. However, the impact of H221Y on NNRTI susceptibility has been poorly characterized, and the interaction of H221Y with other mutations is yet indistinct. 2012 AIDS research and treatment Introduction HIV H221Y;H221Y 23;107 28;112 NNRTI 32 37 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Our previous study showed that the virus carrying K103N/Y181C/H221Y mutation combination could replicate stably in vitro in absence of drugs. 2012 AIDS research and treatment Introduction HIV H221Y;K103N;Y181C 62;50;56 67;55;61 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Several of these mutations, particularly K101E/P and M230L, have been associated with significant resistance to multiple NNRTIs. 2012 AIDS research and treatment Introduction HIV K101E;K101P;M230L 41;41;53 48;48;58 NNRTI 121 127 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. The objective of this study is to clarify the impact of H221Y by itself and combination with other mutations on drug resistance to NVP. 2012 AIDS research and treatment Introduction HIV H221Y 56 61 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. There are four types of NNRTIs-resistant mutations: (1) Primary mutation: these mutations emerge earliest during therapy and cause high-level resistance to one or more NNRTIs, including K103N/S, Y181C/I/V, V106A/M, Y188L/C/H, and G190A/S/E. 2012 AIDS research and treatment Introduction HIV G190A;G190E;G190S;K103N;K103S;V106A;V106M;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 230;230;230;186;186;206;206;195;195;195;215;215;215 239;239;239;193;193;213;213;204;204;204;224;224;224 NNRTI;NNRTI 24;168 30;174 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. These mutations, such as K101Q and V179I, often occur with other primary mutations. 2012 AIDS research and treatment Introduction HIV K101Q;V179I 25;35 30;40 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. This type of mutation consists of A98G, K101Q, V108I, and V179D/E. 2012 AIDS research and treatment Introduction HIV A98G;K101Q;V108I;V179D;V179E 34;40;47;58;58 38;45;52;65;65 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. The dhps mutation at codon 581 is linked with a high rate of therapeutic failure and the emergence of the dhps triple mutant allele (A437G/K540E/A581G) has been confirmed in Tanzania, and the prevalence is increasing. 2012 Malaria journal Introduction HIV A437G;A581G;K540E 133;145;139 138;150;144 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. A cyclobutyl analog of cytosine triphosphate was found to be effective against WT and the M184V drug resistant form of HIV-1 RT. 2012 Bioorganic & medicinal chemistry letters Introduction HIV M184V 90 95 RT 125 127 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. Compound 5 was also more efficiently incorporated compared to the clinically available tenofovir diphosphate 2 with both the wild type and K65R mutant forms of HIV-1 RT. 2012 Bioorganic & medicinal chemistry letters Introduction HIV K65R 139 143 RT 166 168 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. One such mutation is K65R, which causes resistance against tenofovir (TFV or PMPA). 2012 Bioorganic & medicinal chemistry letters Introduction HIV K65R 21 25 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. Recent work has been performed to solve the crystal structures of wild type and the K65R mutant of RT in the presence of a primer-template and dATP or TFV-DP. 2012 Bioorganic & medicinal chemistry letters Introduction HIV K65R 84 88 RT 99 101 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. Similar to the natural substrate and TFV-DP, the K65R mutation greatly decreases the rate of incorporation perhaps in the same manner, through the restriction of the R72 and its interaction with the phosphonate group present in the cyclobutyl compound. 2012 Bioorganic & medicinal chemistry letters Introduction HIV K65R 49 53 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. Upon administration of tenofovir to infected persons, a drug resistant form of HIV-1 RT may arise containing a K65R mutation. 2012 Bioorganic & medicinal chemistry letters Introduction HIV K65R 111 115 RT 85 87 22595174 Pre-steady state kinetic analysis of cyclobutyl derivatives of 2'-deoxyadenosine 5'-triphosphate as inhibitors of HIV-1 reverse transcriptase. We determined the pre-steady state kinetic parameters for the natural substrate dATP, 1, tenofovir diphosphate 2, and the most promising cyclobutyl compound, 5 using the K65R mutant form of HIV-1 RT, as shown in Table 2. 2012 Bioorganic & medicinal chemistry letters Introduction HIV K65R 170 174 RT 196 198 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. From a molecular point of view, it has been demonstrated that the RT KKK nucleotide motif at codons 64, 65, 66 in reverse transcriptase of subtype C HIV-1 appears to lead to template pausing that facilitates the selection of K65R, even in isolates from untreated patients. 2012 PloS one Introduction HIV K65R 225 229 RT;RT 114;66 135;68 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Moreover, it has also been shown that the KKK motif in this subtype can lead to PCR-induced K65R. 2012 PloS one Introduction HIV K65R 92 96 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Regarding K65R, similar studies carried out in the same context of failure on a first-line regimen including d4T, AZT or dideoxyinosine (ddI) showed a prevalence of 4% in a South African population where subtype C was predominant, 10.9% in CRF02_AG plus G viruses in Nigeria, 14% in subtype C isolates from South Africa, 24% in Malawi with subtype C viruses and up to 30% in Botswana. 2012 PloS one Introduction HIV K65R 10 14 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Since we had the prevalence of K65R by the Sanger sequencing method, we investigated K65R variants by ultradeep pyrosequencing (UDPS) in the same samples as those already used for bulk sequencing and sought whether UDPS provided additional knowledge to the Sanger results. 2012 PloS one Introduction HIV K65R;K65R 31;85 35;89 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. TAMs and K65R are known to induce partial or full resistance to TDF. 2012 PloS one Introduction HIV K65R 9 13 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. The aim of the present study was to clarify the prevalence of K65R in these subtype C isolates from patients failing on a first line including d4T or AZT. 2012 PloS one Introduction HIV K65R 62 66 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. We and others have shown that subtype C HIV-1 isolates from Indian patients who fail on first-line HAART composed of stavudine (d4T) or zidovudine (AZT) plus lamivudine (3TC) plus nevirapine (NVP) or efavirenz (EFV) and according to WHO clinical and/or immunological criteria exhibit numerous drug resistance mutations (DRMs) to nucleoside reverse transcriptase inhibitors (NRTIs) and to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the reverse transcriptase (RT) part of the viral genome, including thymidine-associated mutations (TAMs) and K65R (the prevalence of which was around 8% in our series). 2012 PloS one Introduction HIV K65R 557 561 NNRTI;NRTI;RT;NNRTI;NRTI;RT 388;329;452;437;374;475 424;361;473;443;379;477 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. In this report, we have generated a representative three dimensional model of HIV-1 Nef, which was used to predict structural alterations in a HIV-1 Nef SMR-V66A mutant. 2012 Journal of molecular modeling Introduction HIV V66A 157 161 Nef;Nef 84;149 87;152 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. In this study, we sought to determine the virologic outcomes and rate of K65R emergence amongst patients with virologic failure after initiating TDF-containing ART as first-line treatment in a clinic in Durban, South Africa. 2012 AIDS (London, England) Introduction HIV K65R 73 77 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. In vitro studies provide some evidence for more rapid selection of K65R in subtype C virus. 2012 AIDS (London, England) Introduction HIV K65R 67 71 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. The K65R mutation has been reported in 7-15% of patients failing d4T-, ddI- or zidovudine-(AZT) containing first or second-line ART in South Africa, where subtype C accounts for most HIV-1 infections, compared to 2-5% of patients in parts of the world where infection with subtype B dominates. 2012 AIDS (London, England) Introduction HIV K65R 4 8 HIV infections 183 199 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. The reverse transcriptase (RT) mutation K65R results in a four-fold decrease in TDF susceptibility and is selected by TDF, didanosine (ddI), d4T and abacavir (ABC). 2012 AIDS (London, England) Introduction HIV K65R 40 44 RT;RT 4;27 25;29 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. In a series of studies, we demonstrated previously that prolonged tenofovir monotherapy of macaques infected with virulent SIVmac251 or RT-SHIV resulted invariably in the emergence of viral mutants with a K65R mutation in reverse transcriptase. 2012 Retrovirology Introduction HIV K65R 205 209 RT;RT 222;136 243;138 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Such control of viremia was never observed in untreated animals infected with these wild-type or K65R viruses. 2012 Retrovirology Introduction HIV K65R 97 101 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. We report that although one animal gradually lost control on K65R virus replication while still on tenofovir therapy, the other animals resembled long-term non-progressors because their immune system continued to control virus replication even after withdrawal of tenofovir therapy. 2012 Retrovirology Introduction HIV K65R 61 65 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. According to the Stanford HIV Drug Resistance Database (http://hivdb.stanford.edu/; accessed on July 6th, 2012), the frequency of R284K in HIV-1 group M - subtype B RTs found in naive patients is estimated at 1.9%, while this figure goes up to 4.1% when the analysis is carried out with sequences from NRTI-treated individuals. 2012 Retrovirology Introduction HIV R284K 130 135 NRTI;RT 302;165 306;168 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. and Europe showed the significantly higher prevalence of R284K in the treated population and its association with the accumulation of TAMs. 2012 Retrovirology Introduction HIV R284K 57 62 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Enzymological studies provide evidence on the role of R284K as a polymorphism that enhances primer rescue by promoting DNA synthesis after NRTI excision. 2012 Retrovirology Introduction HIV R284K 54 59 NRTI 139 143 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Examples are E312Q, G335C/D, N348I, A360I/V, V365I and A376S in the HIV-1 RT connection subdomain, and Q509L, H539N and D549N in the RNase H domain. 2012 Retrovirology Introduction HIV A360I;A360V;A376S;D549N;E312Q;G335C;G335D;H539N;N348I;Q509L;V365I 36;36;55;120;13;20;20;110;29;103;45 43;43;60;125;18;27;27;115;34;108;50 RT 74 76 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. However, combinations of M41L, D67N, K70R, L210W, T215F/Y and K219E/Q increase ATP-mediated excision of chain-terminating NRTIs (reviewed in ref.). 2012 Retrovirology Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 31;62;62;37;43;25;50;50 35;69;69;41;48;29;57;57 NRTI 122 127 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In this work, we show that R284K is associated with TAM1 mutations in patients failing treatment with tenofovir/emtricitabine-based therapies. 2012 Retrovirology Introduction HIV R284K 27 32 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Mutations such as M184V or M184I conferring resistance to lamivudine or emtricitabine are known to affect nucleotide discrimination. 2012 Retrovirology Introduction HIV M184I;M184V 27;18 32;23 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. N348I or A360V) or its affinity for short RNA/DNA duplexes (e.g. 2012 Retrovirology Introduction HIV A360V;N348I 9;0 14;5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. P272A, R277K and T286A) altered the HIV-1 replication capacity in the presence and in the absence of TAMs, such as M41L and T215Y. 2012 Retrovirology Introduction HIV M41L;R277K;T215Y;T286A;P272A 115;7;124;17;0 119;12;129;22;5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Sequence analysis of HIV-1 isolates from patients receiving long-term therapy with AZT and/or d4T revealed that thymidine analogue resistance mutations (TAMs) acting through the excision mechanism associated in two different clusters: TAM1 (M41L, L210W and T215Y) and TAM2 (D67N, K70R, K219E/Q, and sometimes T215F). 2012 Retrovirology Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 274;286;286;280;247;241;309;257 278;293;293;284;252;245;314;262 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Studies with recombinant HIV-1 have shown that the amino acid substitutions K43E, Q207D and F214L influence the viral replication capacity in the presence of TAMs. 2012 Retrovirology Introduction HIV F214L;K43E;Q207D 92;76;82 97;80;87 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Early work from our lab investigating the influence of Lys65Arg mutations on overall mutation rates and error specificity indicated a qualitative defect in both misinsertion and mismatch extension as seen by a reduction in extension products on the gel based minus dNTP assay. 2012 The FEBS journal Introduction HIV K65R 55 63 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Further investigation into the influence of mutations at Lys65 show that a Lys65Arg mutation conserves polymerase activity similar to wild type, whereas a non-conservative substitution. 2012 The FEBS journal Introduction HIV K65R 75 83 Pol 103 113 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. In the present study, we have investigated the potential role of Lys66 residue in RT fidelity by creating substitutions Lys66Arg, Lys66Ala, Lys66Asn, and Lys66Thr and testing them for both misinsertion and mismatch extension efficiencies. 2012 The FEBS journal Introduction HIV K66A;K66N;K66R;K66T 130;140;120;154 138;148;128;162 RT 82 84 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Leu74Val mutations have shown up to a 6-fold reduction in misinsertion frequency, and a 15-26-fold reduction in mismatch extension frequency. 2012 The FEBS journal Introduction HIV L74V 0 8 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Lys65Ala) results in reduced RT catalytic efficiency (kcat/Km) as well as decreased affinity for dNTP. 2012 The FEBS journal Introduction HIV K65A 0 8 RT 29 31 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Mutations identified among patient isolates at this position include: Lys66Arg, Lys66Asn, Lys66Thr, and Lys66Glu. 2012 The FEBS journal Introduction HIV K66E;K66N;K66R;K66T 104;80;70;90 112;88;78;98 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. showed that the mutation Val75Ile increased the mismatch extension fidelity 3-fold while showing no apparent effect on misinsertion fidelity. 2012 The FEBS journal Introduction HIV V75I 25 33 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. The increased fidelity of the Lys65Ala mutation appears to be directly due to a cumulative effect of a reduction in kpol and increased dNTP Kd in both misinsertion and mismatch extension. 2012 The FEBS journal Introduction HIV K65A 30 38 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. Drug resistant mutation I47V is located in the flexible flap and interacts with inhibitor. 2012 Biochemistry Introduction HIV I47V 24 28 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. Multi-drug-resistant mutation V32I appears in about 20% of patients treated with amprenavir and is associated with high levels of drug resistance to lopinavir/ritonavir. 2012 Biochemistry Introduction HIV V32I 30 34 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. Mutation I47V is associated with resistance to darunavir, lopinavir, tipranavir and ritonavir in therapy. 2012 Biochemistry Introduction HIV I47V 9 13 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. The crystal structures of wild type HIV-1 PR (PRWT) and its mutants containing the single substitutions of I47V (PRI47V) and V32I (PRV32I) were refined at the near-atomic resolutions of 1.2 to 1.4 A and, by serendipity, illustrate three different steps in the hydrolytic reaction. 2012 Biochemistry Introduction HIV I47V;V32I 107;125 111;129 PR;PR;PR 42;113;131 44;115;133 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. In cell-free RT assays the M184V mutant virus exhibits altered enzymatic properties. 2012 Viruses Introduction HIV M184V 27 32 RT 13 15 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. In M184V mutant enzyme, the process of polymerization becomes more accurate; fewer viral variants are produced; and adaptation to environmental stimuli is impaired. 2012 Viruses Introduction HIV M184V 3 8 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Lamivudine (3TC) Resistance:The M184V Substitution. 2012 Viruses Introduction HIV M184V 32 37 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. M184V mutant HIV has been shown to be hypersusceptible to ADV (as well as its successor, tenofovir) in vitro. 2012 Viruses Introduction HIV M184V 0 5 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Since 3TC is known to exert selective pressure on M184V, we would expect inhibition of reversal to wild-type at position 184. 2012 Viruses Introduction HIV M184V 50 55 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The M184V substitution confers the highest level of resistance (up to 1000-fold) for any NRTI that has been described to date. 2012 Viruses Introduction HIV M184V 4 9 NRTI 89 93 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. We hypothesize that if 3TC pressure is withdrawn and at the same time an NNRTI is introduced, then the M184V mutant strains will be at a competitive disadvantage to the more "fit" and "flexible" wild-type variants, which can adapt to the new drug more easily. 2012 Viruses Introduction HIV M184V 103 108 NNRTI 73 78 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. When ADV is added in the absence of 3TC, does ADV select for wild-type virus at position 184? Does the reversal to wild-type virus at position 184 (M184V-reversal) facilitate the development of NVP resistance? 2012 Viruses Introduction HIV M184V 148 153 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. When ADV is added in the absence of 3TC, does ADV select for wild-type virus at position 184? Does the reversal to wild-type virus at position 184 (M184V-reversal) facilitate the development of NVP resistance? . 2012 Viruses Introduction HIV M184V 148 153 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. When HIV-1 is exposed to the NRTI lamivudine (3TC) at inhibitory concentrations, resistant HIV variants carrying the RT substitution M184V (ATGaGTG) emerge rapidly. 2012 Viruses Introduction HIV M184V 133 138 NRTI;RT 29;117 33;119 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. These additional changes cooperate with Y143C, Q148R and N155H to produce more substantial declines in drug susceptibility. 2012 PloS one Introduction HIV N155H;Q148R;Y143C 57;47;40 62;52;45 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. We previously showed that the single amino acid changes Q148R and N155H in HIV-2 integrase confer moderate resistance to raltegravir, whereas the Y143C change had a minimal effect on raltegravir sensitivity. 2012 PloS one Introduction HIV N155H;Q148R;Y143C 66;56;146 71;61;151 IN 81 90 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. E138K and G140S are secondary mutations that develop following the detection of Q148K/R, restoring viral infectivity and replication kinetics. 2012 PloS one Introduction HIV G140S;Q148K;Q148R;E138K 10;80;80;0 15;87;87;5 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. E92Q is also associated with another integrase-inhibitor, elvitegravir. 2012 PloS one Introduction HIV E92Q 0 4 IN 37 46 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Post-raltegravir-therapy evolution of raltegravir-associated DRMs in plasma samples is relatively well-characterized, with reports showing Q148H/K/R+G140S and N155H emerged before Y143R/H/C. 2012 PloS one Introduction HIV G140S;Q148H;Q148K;Q148R;N155H;Y143C;Y143H;Y143R 149;139;139;139;159;180;180;180 154;148;148;148;164;189;189;189 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Well-characterized mutations in the HIV-1 int region that confer high levels of resistance to raltegravir include E92Q, Y143R/H/C, Q148H/K/R and N155H. 2012 PloS one Introduction HIV E92Q;N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 114;145;131;131;131;120;120;120 118;150;140;140;140;129;129;129 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Many resistance mutations have already been characterized including three multi-drug resistance profiles (insertions at codon 69, Q151M-mediated multinucleoside resistance and thymidine analogue mutations (TAM)). 2012 PloS one Introduction HIV Q151M 130 135 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Q151M-associated mutations confer resistance to all nucleoside reverse transcriptase inhibitors (NRTIs) except for tenofovir. 2012 PloS one Introduction HIV Q151M 0 5 NRTI;NRTI 52;97 84;102 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Two distinct TAM resistance pathways can be observed: TAM-1 (M41L, T210W and T215Y) and TAM-2 (D67N, K70R, T215F and K219Q). 2012 PloS one Introduction HIV D67N;K219Q;K70R;M41L;T210W;T215F;T215Y 95;117;101;61;67;107;77 99;122;105;65;72;112;82 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. We could observe a different mutational pattern upon ZDV exposure for subtype B RT variants (TAM-1 pathway; Q151M complex mutations) as compared to subtype C RT variants (TAM-2 pathway). 2012 PloS one Introduction HIV Q151M 108 113 RT;RT 80;158 82;160 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Additionally, a cohort of treatment-naive patients from Mali, West Africa, 71% of whom where CRF02_AG, showed a high prevelance for CN polymorhisms A371V (63%), G335D (76%) and E399D (11%). 2013 Virology Introduction HIV A371V;E399D;G335D 148;177;161 153;182;166 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Associations of these and other CN mutations with drug exposure and TAMs has also been confirmed through other subtype-B-infected patient cohorts and in vitro studies Recently, CN mutation A360V was shown to be selected in subtype-B-infected patients receiving AZT monotherapy. 2013 Virology Introduction HIV A360V 189 194 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Eight novel mutations, E312Q, G335C/D, N348I, A360I/V, V365I, and A376S, were identified within the CN of RT that significantly contributed to AZT resistance, and these mutations were further found to decrease RNase H activity, leading to decreased susceptibility to AZT. 2013 Virology Introduction HIV A360I;A360V;A376S;E312Q;G335C;G335D;N348I;V365I 46;46;66;23;30;30;39;55 53;53;71;28;37;37;44;60 RT 106 108 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Furthermore, 10% of treatment naive subtype C-infected patients from Southern Brazil were shown to already contain CN mutations (for example, T369I and A376S), suggesting that drug therapy may already be compromised in patients harboring CN polymorphisms associated with drug treatment. 2013 Virology Introduction HIV A376S;T369I 152;142 157;147 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Recent data from the Lampang Cohort of CRF01_AE patients failing d4T, 3TC and NVP therapy showed that CN mutations N348I and E399D were associated with treatment failure, and in vitro studies for CRF01_AE viruses containing N348I and A371V in the presence of TAMs also showed enhanced NRTI drug resistance. 2013 Virology Introduction HIV A371V;E399D;N348I;N348I 234;125;115;224 239;130;120;229 NRTI 285 289 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. The recent OPTIMA trial also identified CN mutations Y318F, G333D/E, G335D, N348I, V365I, A371V and A376S as positively associated with treatment experience in a 345 subtype-B-infected patient cohort. 2013 Virology Introduction HIV A371V;A376S;G333D;G333E;G335D;N348I;V365I;Y318F 90;100;60;60;69;76;83;53 95;105;67;67;74;81;88;58 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. We further analyzed 450 subtype B isolates from the Stanford University HIV Drug Resistance Database and showed that 9 CN mutations (I326V, R358K, G359S, A360T, A360V, K366R, A371V, K390R and A400T) and 6 RH mutations (I506L, K512R, K527N, K530R, and Q457K) were positively associated with NRTI or AZT monotherapy exposure. 2013 Virology Introduction HIV A360T;A360V;A371V;A400T;G359S;I326V;I506L;K366R;K390R;K512R;K527N;K530R;Q457K;R358K 154;161;175;192;147;133;219;168;182;226;233;240;251;140 159;166;180;197;152;138;224;173;187;231;238;245;256;145 NRTI 290 294 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. We have previously reported that CN mutation A400T in CRF01_AE is an important determinant for AZT resistance in CRF01_AE patients containing TAMs. 2013 Virology Introduction HIV A400T 45 50 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Using a panel of recombinant INs that carry the Y143R, N155H and G140S-Q148H mutations, we reported that elvitegravir (EVG, Gilead Sciences), dolutegravir (DTG, ViiV Healthcare/Shionogi) and MK-0536 (Merck & Co.) retain high efficacy against these RAL-resistant mutants. 2013 ACS chemical biology Introduction HIV G140S;N155H;Q148H;Y143R 65;55;71;48 70;60;76;53 IN 29 32 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. 4'-Ed4T induced a resistant virus harboring three mutations (P119S, T165A, and M184V) on day 81 (4'-ethynylstavudine81D), yet 4'-ethynylstavudine still retained sufficient anti-HIV-1 activity against this mutant. 2013 Current pharmaceutical design Introduction HIV M184V;P119S;T165A 79;61;68 84;66;73 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. 4'-ethynylstavudine also induced a virus harboring the M184V mutation on day 26 (4'-Ed4T26D), which was 1.7-fold less susceptible to the compound. 2013 Current pharmaceutical design Introduction HIV M184V 55 60 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. 4'-ethynylstavudine was 6.7-, 10-, and 2.9-fold less active against A012D and the M184V mutants of HXB-2 and NL4-3 compared to the wild-type, respectively (Table 5). 2013 Current pharmaceutical design Introduction HIV M184V 82 87 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. A012D contains four NRTI-associated mutations (NAMs) (D67K, K70R, T215F and K219Q), which confer a high level (210-fold) resistance to zidovudine. 2013 Current pharmaceutical design Introduction HIV D67K;K219Q;K70R;T215F 54;76;60;66 58;81;64;71 NRTI 20 24 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Among the mutations, N348I and A360V in the connection domain contribute to increasing resistance to zidovudine. 2013 Current pharmaceutical design Introduction HIV A360V;N348I 31;21 36;26 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Compared with wild type virus, variants with single RT mutations (P119S or T165A) did not show resistance to 4'-ethynylstavudine, however, the M184V and P119S/T165A/M184V strains conferred 3- and 5-fold resistance, respectively. 2013 Current pharmaceutical design Introduction HIV M184V;P119S;T165A;M184V;P119S;T165A 165;153;159;143;66;75 170;158;164;148;72;80 RT 52 54 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Could the previously observed 130-fold resistance of the P119S/T165A/M184V virus to 4'-ethynylstavudine be due to additional mutations in the RT and/or outside the RT sequence, or that this virus is either difficult to recover from storage due to a poor replication capacity? Based on recent studies and the structural modeling of interaction of HIV RT-primer complex and 4'-Ed4TTP, a virus with a high degree of resistance to 4'-ethynylstavudine (e.g., more that 50-fold resistance, highly resistant to 4'-ethynylstavudine) will be difficult to develop. 2013 Current pharmaceutical design Introduction HIV M184V;P119S;T165A 69;57;63 74;62;68 RT;RT;RT 142;164;350 144;166;352 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. In fact, nevirapine (NVP) was 55- and 70-fold less active against the K103N mutants of HXB-2 and NL4-3, respectively (Table 5). 2013 Current pharmaceutical design Introduction HIV K103N 70 75 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Lamivudine induced a virus harboring the M184V mutation on day 29 (3TC29D), and the mutant was completely resistant to lamivudine (Table 7). 2013 Current pharmaceutical design Introduction HIV M184V 41 46 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. M184V could affect the binding of incoming dNTP due to a gap created between the polymerase and the DNA minor groove of the nascent base pair leading to 3 to 5-fold resistance to 4'-Ed4T. 2013 Current pharmaceutical design Introduction HIV M184V 0 5 Pol 81 91 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Moreover, the strains carrying the K65R or the Q151M complex were still susceptible to 4'-ethynylstavudine. 2013 Current pharmaceutical design Introduction HIV K65R;Q151M 35;47 39;52 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. presented above, M184V mutation was observed on the 26th day and two additional mutations (P119S and T165A) of HIV RT were found on day 81. 2013 Current pharmaceutical design Introduction HIV M184V;P119S;T165A 17;91;101 22;97;106 RT 115 117 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The K103N mutation confers a high level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). 2013 Current pharmaceutical design Introduction HIV K103N 4 9 NNRTI;NNRTI 54;103 90;109 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The K65R mutation confers resistance to tenofovir and some NRTIs and, the Q151M complex (A62V, V75I, F77L, F116Y, and Q151M) confers resistance to most of the clinically approved NRTIs. 2013 Current pharmaceutical design Introduction HIV A62V;F116Y;F77L;K65R;Q151M;Q151M;V75I 89;107;101;4;74;118;95 93;112;105;8;79;123;99 NRTI;NRTI 59;179 64;184 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The M184V and triple (M184V/P119S/T165A) mutants were reported to confer 3-5-fold and 130-fold resistance to 4'-ethynylstavudine, respectively. 2013 Current pharmaceutical design Introduction HIV M184V;P119S;T165A;M184V 22;28;34;4 27;33;39;9 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The M184V mutation in reverse transcriptase (RT) also confers a high level resistance to lamivudine. 2013 Current pharmaceutical design Introduction HIV M184V 4 9 RT;RT 22;45 43;47 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The N348I and A360V mutations confer resistance to zidovudine by increasing excision of incorporated zidovudine through RNase H-dependent and independent mechanism. 2013 Current pharmaceutical design Introduction HIV A360V;N348I 14;4 19;9 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The N348I mutation was reported to be highly correlated with the M184V/I mutation. 2013 Current pharmaceutical design Introduction HIV M184I;M184V;N348I 65;65;4 72;72;9 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The P119S/M184V and T165A/M184V variants showed about 4-fold resistance to 4'-ethynylstavudine. 2013 Current pharmaceutical design Introduction HIV M184V;M184V;P119S;T165A 10;26;4;20 15;31;9;25 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. The purified RT with P119S/M184V and T165A/M184V mutations were inhibited by 4'-Ed4TTP with 8 to13-fold less efficiency than wild type RT. 2013 Current pharmaceutical design Introduction HIV M184V;M184V;P119S;T165A 27;43;21;37 32;48;26;42 RT;RT 13;135 15;137 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Therefore, the P119S, T165A, and M184V mutations were engineered into NL4-3 background to assess the contribution of each of these mutations to drug resistance, RT activity, and viral growth. 2013 Current pharmaceutical design Introduction HIV M184V;P119S;T165A 33;15;22 38;20;27 RT 161 163 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. These residues are highly conserved, and mutations at this pocket (A114M, A114L, Y115Q, F160A, F160L, and M184F) except M184V and M184A caused complete loss of RT activity. 2013 Current pharmaceutical design Introduction HIV A114L;A114M;F160A;F160L;M184A;M184F;M184V;Y115Q 74;67;88;95;130;106;120;81 79;72;93;100;135;111;125;86 RT 160 162 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. This compound has several additional advantages as a promising anti-HIV-1 agent: 1) it is a better substrate for human thymidine kinase than stavudine, 2) it is very much more resistant to catabolism by thymidine phosphorylase, and 3) its anti-HIV activity is enhanced in the presence of a major mutation K103N, associated with resistance non-nucleoside reverse transcriptase inhibitors. 2013 Current pharmaceutical design Introduction HIV K103N 305 310 NNRTI 339 375 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. This was puzzling as the P119S and/or T165A have not been observed previously in HIV-1-infected individuals. 2013 Current pharmaceutical design Introduction HIV P119S;T165A 25;38 30;43 HIV infections 81 95 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. We surmise that clinical resistance to 4'-ethynylstavudine will be difficult to emerge in clinical studies with relevant dosage which will suppress M184V mutant virus, prerequisite for developing highly 4'-ethynylstavudine resistant virus if the initial resistance selection holds. 2013 Current pharmaceutical design Introduction HIV M184V 148 153 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. When the previous HIV resistant strain (P119S/T165A/M184V), with 130-fold resistance to 4'-ethynylstavudine, was recovered by Prof. 2013 Current pharmaceutical design Introduction HIV M184V;P119S;T165A 52;40;46 57;45;51 23092278 From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. While zidovudine, stavudine, didanosine, and lamivudine were 440-, 8.4-, 14- and 2.8-fold less active against the Q15M mutant of HXB-2, respectively, 4'-ethynyl-stavudine retained potent anti-HIV-1 activity against the mutants harboring the Q151M or K65R mutation (Table 5). 2013 Current pharmaceutical design Introduction HIV K65R;Q151M;Q15M 250;241;114 254;246;118 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. In the present study, we have tested the SWCNTs as inhibitors in WT as well as in three primary mutants (I50VPR, V82APR and I84VPR) of HIV-1-PR by docking the SWCNT in the active site region, and then performed all-atom molecular dynamics (MD) simulations for the complexes. 2012 Journal of molecular graphics & modelling Introduction HIV I50V;I84V;V82A 105;124;113 111;130;119 PR 141 143 23144597 Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation. Flap+ is a multi-drug-resistant HIV-1 protease variant with a combination of flap and active site mutations (L10I, G48V, I54V, and V82A) that occur simultaneously in sequences of patients undergoing drug therapy (Figure 1). 2012 Journal of chemical theory and computation Introduction HIV G48V;I54V;L10I;V82A 115;121;109;131 119;125;113;135 PR 38 46 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. found that introducing the T216I and R132T suppressor mutations in HIV CA restored infectivity to both the P38A and the E45A mutant viruses. 2013 Virology Introduction HIV E45A;P38A;R132T;T216I 120;107;37;27 124;111;42;32 Capsid 71 73 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. In an in vitro uncoating assay, the P38A mutation rendered the HIV CA core unstable, but the E45A mutation resulted in a hyperstable core. 2013 Virology Introduction HIV E45A;P38A 93;36 97;40 Capsid 67 69 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Early virological failure on a nucleoside reverse transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen is associated with emergence of the M184V mutation and an NNRTI resistance mutation in approximately 50-75% of patients in resource-rich settings. 2012 PloS one Introduction HIV M184V 183 188 NNRTI;NRTI;NNRTI;NNRTI;NRTI 85;31;132;205;75 120;63;137;210;79 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Additionally, the effect of individual mutations I54V versus I54A on inhibitor binding is compared. 2013 ACS chemical biology Introduction HIV I54A;I54V 61;49 65;53 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Analysis of patient sequences in the Stanford HIV drug resistance database revealed that I54A also shares many of the mutations frequently observed together with I54V (detailed analysis in Supplementary Information). 2013 ACS chemical biology Introduction HIV I54A;I54V 89;162 93;166 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. As mentioned previously, the binding of Flap+(I54V) to both APV and DRV was enthalpically unfavorable, and these reactions were entirely driven by the entropy of binding (Table 1). 2013 ACS chemical biology Introduction HIV I54V 46 50 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. As with APV, only the Flap+(I54V) variant had an unfavorable binding enthalpy to DRV. 2013 ACS chemical biology Introduction HIV I54V 28 32 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Besides G48V or I54V, Flap+(I54V) has an additional active site mutation V82A, as does Flap+(I54A). 2013 ACS chemical biology Introduction HIV G48V;I54A;I54V;I54V;V82A 8;93;16;28;73 12;97;20;32;77 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Binding thermodynamics of the two Flap+ variants and three single mutants (I54V, I54A, G48V) were measured by isothermal titration calorimetry for the protease inhibitors saquinavir (SQV), amprenavir (APV), and darunavir (DRV) (Table 1. 2013 ACS chemical biology Introduction HIV G48V;I54A;I54V 87;81;75 91;85;79 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Both G48V and V82A are associated with SQV resistance. 2013 ACS chemical biology Introduction HIV G48V;V82A 5;14 9;18 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Both single I54 mutants caused about a 2-fold affinity lost, while G48V decreased DRV susceptibility 16-fold. 2013 ACS chemical biology Introduction HIV G48V 67 71 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Curiously, as we previously reported, Flap+(I54V) exhibits extreme entropy-enthalpy compensation with respect to wild-type enzyme, regardless of the inhibitor bound. 2013 ACS chemical biology Introduction HIV I54V 44 48 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. DRV binding to I54V and I54A mutants had comparable free energies, -14.8 and -14.7 kcal mol-1, respectively, yet with varied enthalpic and entropic contributions. 2013 ACS chemical biology Introduction HIV I54A;I54V 24;15 28;19 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Flap+(I54V) is a drug resistant protease variant containing a combination of active site and flap mutations (L10I/G48V/I54V/V82A) (Figure 1) that often occur together in treated patients. 2013 ACS chemical biology Introduction HIV G48V;I54V;L10I;V82A;I54V 114;119;109;124;6 118;123;113;128;10 PR 32 40 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Flap+(I54V) was also unique in being the only variant which had an unfavorable binding enthalpy to both APV and DRV, while all other variants bound with favorable enthalpy and entropy (Table 1). 2013 ACS chemical biology Introduction HIV I54V 6 10 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. G48V and I54V altered the enthalpy and entropy of binding to APV by less than 1 kcal mol-1. 2013 ACS chemical biology Introduction HIV I54V;G48V 9;0 13;4 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Hence, mutations in Flap+(I54V) cooperatively altered the binding thermodynamics for both APV and DRV binding, yielding solely entropy-driven inhibitor binding by this variant. 2013 ACS chemical biology Introduction HIV I54V 26 30 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Hence, the combination of mutations in the variants studied here, Flap+(I54V) and Flap+(I54A) (L10I/G48V/I54A/V82A), are clinically relevant and correlated. 2013 ACS chemical biology Introduction HIV G48V;I54A;L10I;V82A;I54A;I54V 100;105;95;110;88;72 104;109;99;114;92;76 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Hence, the observed cooperativity of G48V and I54V mutations is most likely caused by their effects on flap dynamics. 2013 ACS chemical biology Introduction HIV G48V;I54V 37;46 41;50 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Here, we found I54A to similarly impair SQV binding, decreasing affinity 47-fold relative to wild-type protease. 2013 ACS chemical biology Introduction HIV I54A 15 19 PR 103 111 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. However, I54V in the Flap+ background results in a much larger effect than a simple addition of individual mutations. 2013 ACS chemical biology Introduction HIV I54V 9 13 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. However, the enthalpy and entropy of binding to the same inhibitor for Flap+(I54V) changed by 11 and 10 kcal mol-1, respectively. 2013 ACS chemical biology Introduction HIV I54V 77 81 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. However, the enthalpy of binding to APV was 10 kcal mol changed by 11 and 10 kcal mol-1 less favorable for Flap+(I54V) than for Flap+(I54A), and the entropy of binding was 10 kcal mol-1 more favorable (Figure 2). 2013 ACS chemical biology Introduction HIV I54A;I54V 134;113 138;117 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. However, these dramatic changes in the enthalpy and entropy of binding for Flap+(I54V) are not due to the V82A mutation, because these changes are much less pronounced for the binding of the same inhibitors to Flap+(I54A), which contains the same additional mutation. 2013 ACS chemical biology Introduction HIV I54A;I54V;V82A 216;81;106 220;85;110 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. I54A has a PI susceptibility profile similar to I54V, unlike other substitutions such as I54L and I54M. 2013 ACS chemical biology Introduction HIV I54L;I54M;I54V;I54A 89;98;48;0 93;102;52;4 PI 11 13 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. I54V mutation may be destabilizing this minor conformation, further restricting the conformational range of the flaps. 2013 ACS chemical biology Introduction HIV I54V 0 4 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. I54V on the other hand, caused a 1.9-fold decrease in affinity. 2013 ACS chemical biology Introduction HIV I54V 0 4 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. In contrast, the enthalpic and entropic components of binding contributed approximately equally to the free energy of binding between Flap+(I54A) and APV or DRV. 2013 ACS chemical biology Introduction HIV I54A 140 144 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. In most of the patients with known preceding sequences, I54A evolves from I54V (Table S1). 2013 ACS chemical biology Introduction HIV I54A;I54V 56;74 60;78 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. In striking contrast, however, Flap+(I54V) lost 3-fold affinity to APV binding, even though G48V alone did not have any considerable effect on binding affinity (0.9-fold relative to WT). 2013 ACS chemical biology Introduction HIV G48V;I54V 92;37 96;41 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. In the present letter, the extraordinary thermodynamic behavior of Flap+(I54V) is compared with that of Flap+(I54A). 2013 ACS chemical biology Introduction HIV I54A;I54V 110;73 114;77 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. In the WT protease background, single mutations I54A and I54V had the opposite effect on APV susceptibility, with I54V rendering the enzyme hyper-susceptible by 0.3-fold. 2013 ACS chemical biology Introduction HIV I54A;I54V;I54V 48;57;114 52;61;118 PR 10 18 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Interestingly, Flap+(I54V) binding to APV and DRV had relative enthalpic and entropic contributions similar to WT protease binding to the first-generation inhibitor SQV. 2013 ACS chemical biology Introduction HIV I54V 21 25 PR 114 122 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Similarly, in the case of DRV, the enthalpy of binding to Flap+(I54V) was 9 kcal mol-1 less favorable and the entropy of binding was 9 kcal mol-1 more favorable than binding to Flap+(I54A). 2013 ACS chemical biology Introduction HIV I54A;I54V 183;64 187;68 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. The change in flap dynamics due to I54V and G48V mutations has recently been confirmed for unliganded Flap+(I54V) by MD and NMR studies. 2013 ACS chemical biology Introduction HIV G48V;I54V;I54V 44;35;108 48;39;112 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. The changes in thermodynamic parameters with respect to WT protease (Figure 2) further illustrate that the combined effect of mutations in Flap+(I54V) is greater than a simple summation of the changes induced by the individual mutations G48V and I54V. 2013 ACS chemical biology Introduction HIV G48V;I54V;I54V 237;145;246 241;149;250 PR 59 67 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. The entropy-driven binding and the large cooperative entropy enhancement upon simultaneous G48V/I54V mutations could, in theory, be due to either enhancement of solvation entropy or conformational dynamics. 2013 ACS chemical biology Introduction HIV G48V;I54V 91;96 95;100 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. There are significant differences in the enthalpy and entropy of binding, despite only small differences between the free energy of binding to any inhibitor for Flap+(I54V) and Flap+(I54A), only 0.2 and 0.6 kcal mol changed by 11 and 10 kcal mol-1 for APV and DRV, respectively. 2013 ACS chemical biology Introduction HIV I54A;I54V 183;167 187;171 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. These drastic differences between Flap+(I54V) and Flap+(I54A) clearly indicate that relatively small changes at Ile54 can alter binding of inhibitors. 2013 ACS chemical biology Introduction HIV I54A;I54V 56;40 60;44 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. This cooperative effect of mutations in Flap+(I54V) has also been observed for APV binding. 2013 ACS chemical biology Introduction HIV I54V 46 50 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. This cooperative effect was also observed for binding DRV: Flap+(I54V) had a larger change in enthalpy and entropy with respect to WT (14.1 and -13.1, kcal mol-1, respectively) than the sum of the changes observed for G48V or I54V (Figure 2). 2013 ACS chemical biology Introduction HIV G48V;I54V;I54V 218;65;226 222;69;230 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. This decrease in SQV affinity in Flap+(I54A) is consistent with an approximately additive effect of single mutations I54A and G48V. 2013 ACS chemical biology Introduction HIV G48V;I54A;I54A 126;39;117 130;43;121 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Thus, the extreme entropy-enthalpy compensation previously reported for Flap+(I54V) is not due to any individual mutation or a simple additive effect of these mutations, but rather a result of cooperative effects when both flap mutations, G48V and I54V, simultaneously occur. 2013 ACS chemical biology Introduction HIV G48V;I54V;I54V 239;78;248 243;82;252 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. Two mutations in the flap region, G48V and I54V, have been well correlated with drug resistance to multiple inhibitors, even though Ile54 does not contact either substrates or inhibitors. 2013 ACS chemical biology Introduction HIV G48V;I54V 34;43 38;47 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. When Flap+(I54V) is compared with Flap+(I54A), the extreme entropy-enthalpy compensation and considerable amount of the cooperativity is lost upon shortening of the side chain not in contact with the inhibitors. 2013 ACS chemical biology Introduction HIV I54A;I54V 40;11 44;15 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. When these same Ile54 mutations were present in the background of Flap+ variants, SQV binding affinity was impaired by 3 orders of magnitude (880 and 170-fold for Flap+(I54A) and Flap+(I54V), respectively). 2013 ACS chemical biology Introduction HIV I54A;I54V 169;185 173;189 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Major mutations remain uncommon in the antiretroviral treatment naive patients; so far only a few cases of transmitted drug resistance (Q148H, G140S and N155H mutations) have been described . 2012 BMC infectious diseases Introduction HIV G140S;N155H;Q148H 143;153;136 148;158;141 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. On the other hand, polymorphic mutations in the central core domain positions have been observed in up to 34% of the published sequences and 56% of the patients with recently acquired infection ; some of these naturally occurring variants have been observed in patients failing raltegravir and elvitegravir (L74M, T97A, S119G/R, E157Q, G163K/R), with notable the frequency variation across the subtypes . 2012 BMC infectious diseases Introduction HIV E157Q;G163K;G163R;L74M;S119G;S119R;T97A 330;337;337;309;321;321;315 335;344;344;313;328;328;319 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Virologic failure has been associated with major, signature mutations within the catalytic domain of the enzyme, and include Y143R/C, N155H Q148K/R/H integrase sequence variants associated with significant susceptibility reduction both to RAL and elvitegravir (EVG) . 2012 BMC infectious diseases Introduction HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 134;140;140;140;125;125 139;149;149;149;132;132 IN 150 159 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. In this study we determine the ability of TDRTIs to block reverse transcription by the multi-drug resistant N348I HIV-1 RT as well as other NRTI resistant RTs, D67N/K70R/L210Q/T215F (resistant to AZT by the excision mechanism) D67N/K70R/L210Q/T215F/N348I, and A62V/V75I/F77L/F116Y/Q151M (multidrug resistant to AZT and dideoxynucleotide RT inhibitors). 2012 Cellular and molecular biology (Noisy-le-Grand, France) Introduction HIV A62V;D67N;D67N;F116Y;F77L;K70R;K70R;L210Q;L210Q;N348I;Q151M;T215F;T215F;V75I;N348I 260;160;227;275;270;165;232;170;237;249;281;176;243;265;108 264;164;231;280;274;169;236;175;242;254;286;181;248;269;113 RT;NRTI;RT;RT;RT 58;140;120;155;337 79;144;122;158;339 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Moreover, the N348I mutation increased nucleic acid binding affinity, enhanced processivity and lowered the catalytic turnover rate of the natural substrate. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Introduction HIV N348I 14 19 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Recently, using transient-state kinetic experiments we established the mechanism of NNRTI resistance of HIV-1 RT containing the N348I mutation at the connection subdomain of the enzyme. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Introduction HIV N348I 128 133 NNRTI;RT 84;110 89;112 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The most significant of these mutations is N348I, which confers moderate resistance to both NRTIs and NNRTIs, and is present in a significant number of clinical isolates, especially in the presence of other NRTI mutations. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Introduction HIV N348I 43 48 NNRTI;NRTI;NRTI 102;92;207 108;97;211 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. D30N is a major mutation that is associated with resistance to nelfinavir (NFV). 2013 Journal of medicinal chemistry Introduction HIV D30N 0 4 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. I50V also has a significant effect in destabilizing the PR dimer. 2013 Journal of medicinal chemistry Introduction HIV I50V 0 4 PR 56 58 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. In order to study the molecular basis for the potency of inhibitor 1 against drug resistant viral strains, crystal structures of inhibitor 1 complexes with PR mutants bearing single substitutions of R8Q, D30N, I50V, I54M and V82A (PRR8Q, PRD30N, PRI50V, PRI54M and PRV82A) were analyzed. 2013 Journal of medicinal chemistry Introduction HIV D30N;I50V;I54M;R8Q;V82A 204;210;216;199;225 208;214;220;202;229 PR;PR;PR;PR;PR;PR 156;231;238;246;254;265 158;233;240;248;256;267 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Indeed, PR with I50V mutation exhibits significantly reduced inhibition by indinavir, SQV, and DRV. 2013 Journal of medicinal chemistry Introduction HIV I50V 16 20 PR 8 10 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutation of I50V to a shorter side chain is expected to reduce the binding affinity for inhibitors. 2013 Journal of medicinal chemistry Introduction HIV I50V 12 16 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. R8Q was one of the first resistant mutants identified in the laboratory for an investigational inhibitor. 2013 Journal of medicinal chemistry Introduction HIV R8Q 0 3 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. The mutation V82A in the active site cavity can eliminate interactions with inhibitor, and also exhibits a shift of its main chain atoms to adapt to inhibitor. 2013 Journal of medicinal chemistry Introduction HIV V82A 13 17 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Therefore, it is of particular interest to test how the R8Q mutation affects the binding of inhibitor 1. 2013 Journal of medicinal chemistry Introduction HIV R8Q 56 59 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. These mutations, with the exception of R8Q, are common in drug resistant clinical isolates. 2013 Journal of medicinal chemistry Introduction HIV R8Q 39 42 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. This intersubunit ionic interaction was eliminated in the mutant with the single substitution of R8Q. 2013 Journal of medicinal chemistry Introduction HIV R8Q 97 100 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. A particularly troublesome mutation has been Tyr181Cys (Y181C), which often arises quickly in patients who begin NNRTI therapy. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C;Y181C 45;56 54;61 NNRTI 113 118 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. For 1f, the potency towards the WT and Y181C variant form of HIV-1 are essentially the same, in sharp contrast to the case for the parent 1b. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 39 44 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. For the Y181C HIV-1 variant, it was gratifying that the qualitative predictions from the MC/FEP calculations were confirmed. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 8 13 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. However, as illustrated for the case with R = ethyl in Figure 1, it was expected that a group such as ethyl or propyl might constructively occupy the space vacated by the Tyr181 to Cys181 change. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 171 187 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. In comparison to 2a, addition of the ethyl group provides a 5-fold activity boost against the WT virus and a 50-fold gain against the Y181C-bearing variant. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 134 139 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. In summary, further study of oxazoles 1 as NNRTIs has focused on optimization of the 4-R group to yield greater potency against strains of HIV-1 containing the Tyr181Cys mutation in the reverse transcriptase enzyme. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 160 169 RT;NNRTI 186;43 207;49 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. Indeed, there is pronounced improvement in the activity towards the Y181C-containing virus peaking with the ethyl and isopropyl analogs 1e and 1f with EC50s of 7 nM. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 68 73 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. Specifically, 1a (R = X = H) has an EC50 of 13 nM towards wild-type HIV-1, but shows no activity towards a Y181C-containing strain. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 107 112 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. The cyclopropyl compound is less active against the WT virus by a factor of 5 and 200-fold less active towards the Y181C variant. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 115 120 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. The first generation drugs, nevirapine and delavirdine, are inactive towards HIV-1 strains with this mutation, and the second-generation efavirenz is debilitated by Y181C when combined with Lys103Asn. 2013 Bioorganic & medicinal chemistry letters Introduction HIV K103N;Y181C 190;165 199;170 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. The MC/FEP calculations were carried out for both the WT and Y181C variant of HIV-RT with MCPRO; the resultant relative free energies of binding are summarized in Table 1. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 61 66 RT 82 84 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. The strategy was to seek improved Y181C activity, even if there is some loss of WT activity. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 34 39 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. The X = Cl analog 1b fares only a little better with EC50s of 6 nM for the WT virus and 420 nM for the Y181C variant. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 103 108 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. The Y181C variant has always been problematic and it has required deliberate efforts to overcome. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 4 9 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. The Y181C variant was generated manually from the WT structure and all complexes were relaxed with short conjugate gradient minimizations. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 4 9 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. Then, the results for the Y181C variant are striking with the prediction that there would be significantly greater gain than for the WT enzyme and that peak binding should occur for R = isopropyl. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 26 31 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. There is also improvement in potency towards the challenging K103N/Y181C double mutant. 2013 Bioorganic & medicinal chemistry letters Introduction HIV K103N;Y181C 61;67 66;72 23298809 Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. Thus, the expectation was that for R = Et and i-Pr, the WT activity should be good relative to R = H, but there should be significantly greater gains in potency towards the Y181C-bearing virus. 2013 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 173 178 PR 48 50 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. A lysine to arginine mutation at position 65 of the RT (K65R), which confers a two- to four-fold decrease in susceptibility to tenofovir, is included on all drug resistance lists and has historically been considered the classic tenofovir-associated mutation. 2012 Journal of the International AIDS Society Introduction HIV K65R;K65R 56;2 60;44 RT 52 54 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. K65R may be more likely to develop in subtype C, due to the nucleic acid variation surrounding this codon. 2012 Journal of the International AIDS Society Introduction HIV K65R 0 4 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. The reported prevalence of transmitted K65R is low. 2012 Journal of the International AIDS Society Introduction HIV K65R 39 43 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. We determined the prevalence of K65R and other mutations associated with tenofovir resistance by direct examination of RT sequences from treatment-naive individuals across different HIV-1 subtypes and recombinant forms. 2012 Journal of the International AIDS Society Introduction HIV K65R 32 36 RT 119 121 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Firstly, in the MONARK study, assessing lopinavir monotherapy in antiretroviral-naive patients, the prevalence of the L76V in case of virological failure was 9.4% in this study and all patients displaying L76V-mutated viruses at failure were infected with CRF02_AG recombinant. 2013 PloS one Introduction HIV L76V;L76V 118;205 122;209 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. However, a novel resistance pathway involving the protease mutation L76V was recently described both in antiretroviral-naive patients and in antiretroviral-experienced patients. 2013 PloS one Introduction HIV L76V 68 72 PR 50 58 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. However, few data are available on the impact of the viral subtype on the selection of the L76V mutation. 2013 PloS one Introduction HIV L76V 91 95 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In a study assessing genotypic resistance profiles in 57 patients living in Cameroon, all infected with HIV-1 "non-B" subtypes, the prevalence of the L76V was 8.8%. 2013 PloS one Introduction HIV L76V 150 154 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In addition, the L76V is associated with an in vitro hypersusceptibility to saquinavir, atazanavir, and tipranavir. 2013 PloS one Introduction HIV L76V 17 21 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Some studies reported a high prevalence of L76V in "non-B" subtypes, particularly in the CRF02_AG recombinant. 2013 PloS one Introduction HIV L76V 43 47 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The aim of the study was to describe the L76V protease mutation in term of prevalence, patients characteristics, and PI RAM clustering with the L76V mutation in the context of HIV-1 B subtype and HIV-1 "non-B" subtypes. 2013 PloS one Introduction HIV L76V;L76V 41;144 45;148 PR;PI 46;117 54;119 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The L76V is a drug resistance mutation associated with resistance to lopinavir, darunavir, fosamprenavir and indinavir. 2013 PloS one Introduction HIV L76V 4 8 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The prevalence of the L76V mutation in PI-resistant viruses was found about 3.3% in two large databases of clinical sequences, with no viral subtype sub-analysis. 2013 PloS one Introduction HIV L76V 22 26 PI 39 41 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Among these residues, N43D in the N-HR is one of the representative mutations for resistance to T-20. 2013 The international journal of biochemistry & cell biology Introduction HIV N43D 22 26 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. E137K, a C-HR mutation located in the T-20 sequence, improved replication kinetics and enhanced affinity to N-HR, indicating that E137K acts as a secondary mutation. 2013 The international journal of biochemistry & cell biology Introduction HIV E137K;E137K 130;0 135;5 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Furthermore, the I37N and L33S mutations appeared to act as primary mutations for wild-type and T-20-resistant HIV-1, respectively. 2013 The international journal of biochemistry & cell biology Introduction HIV I37N;L33S 17;26 21;30 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. In this case, we designed a variant of C34 carrying a secondary escape mutation, N126K, selected for the induction of C34 resistance and also present in HIV-1 isolates from T-20 experienced patients. 2013 The international journal of biochemistry & cell biology Introduction HIV N126K 81 86 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Interestingly, most variants show impaired replication fitness, and thus often go on to acquire secondary mutations, such as S138A, in the C-HR region of gp41 that corresponds to the sequence of T-20. 2013 The international journal of biochemistry & cell biology Introduction HIV S138A 125 130 gp41 154 158 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Introducing the E137K change into the T-20S138A (T-20E137K/S138A) resulted into a peptide inhibitor effective against T-20S138A-resistant variants, suggesting that secondary or compensatory mutations can be widely applicable to the design of next generation peptide-based inhibitors that are active against HIV-1 resistant to earlier generation fusion-targeting drugs. 2013 The international journal of biochemistry & cell biology Introduction HIV E137K;S138A;E137K;S138A 53;122;16;59 58;127;21;64 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. To preempt this escape strategy, we have previously designed a peptide analog of T-20 with the S138A change incorporated in it (T-20S138A. 2013 The international journal of biochemistry & cell biology Introduction HIV S138A;S138A 132;95 137;100 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Using circular dichroism (CD) and structural analyses, we also demonstrated that the S138A change provided increased stability to the six-helix bundle. 2013 The international journal of biochemistry & cell biology Introduction HIV S138A 85 90 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We and others have recently demonstrated that S138A functions as secondary resistance mutation and enhances resistance to T-20 by restoring impaired replication kinetics of T-20-resistant variants that contain primary mutations in the N-HR region, most notably N43D. 2013 The international journal of biochemistry & cell biology Introduction HIV N43D;S138A 261;46 265;51 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. At the same time, this switch would obviate the problem of initiating therapy with an rilpivirine-based regimen at high viral loads and presumably avoid the problem of M184I/E138K drug resistance in such populations. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV E138K;M184I 174;168 179;173 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. E138K is known to confer resistance against all members of the non-NRTI family of drugs, including etravirine and rilpivirine, but the appearance of E138K has not commonly been seen for other non-NRTIs except in tissue culture studies. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV E138K;E138K 149;0 154;5 NNRTI;NNRTI 63;192 71;201 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. Furthermore, patients with virologic failure on rilpivirine in ECHO and THRIVE did not have K103N mutations, and this finding is not unexpected because rilpivirine does not select for the K103N mutation in tissue culture. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV K103N;K103N 92;188 97;193 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. However, these two agents have a low barrier to the development of resistance, because a single mutation within this pocket (eg, K103N) can render both drugs ineffective. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV K103N 129 134 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. In contrast, other mutations such as Y181C that diminish sensitivity to efavirenz and nevirapine can also cause cross-resistance to rilpivirine. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV Y181C 37 42 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. In general, rilpivirine-treated patients also had higher rates of virologic failure than efavirenz-treated patients in the Phase III ECHO and THRIVE trials, ie, 10% versus 6%, and Table 2 shows that the most common mutations among the rilpivirine failures were E138K and M184I. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV E138K;M184I 261;271 266;276 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. Information is lacking in regard to the use of rilpivirine in combination with protease inhibitors, integrase inhibitors, and other classes of antiretrovirals, and tissue culture data indicate that rilpivirine is unaffected by some of the resistance-associated mutations, including K103N, that markedly impair the activity of efavirenz and nevirapine. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV K103N 282 287 IN;PR 100;79 109;87 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. It also follows that rilpivirine should be expected to be useful in patients who possess K103N at baseline due to transmitted resistance. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV K103N 89 94 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. Nonetheless, it does not appear likely that patients who fail a first-line rilpivirine-based regimen with the E138K mutation will be able to benefit from etravirine if the latter drug is included in a second-line regimen. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV E138K 110 115 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. Seemingly, the E138K mutation can compensate for the fitness deficits of both M184I and M184V, thus restoring the replicative capacity of viruses containing M184I/V together with E138K, and the absence of M184V in the ECHO and THRIVE trials seems attributable to the stabilization effect of E138K on viruses containing M184I, thus obviating the need for development of the M184V mutation. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV E138K;E138K;E138K;M184I;M184I;M184I;M184V;M184V;M184V;M184V 15;179;291;78;157;319;88;157;205;373 20;184;296;83;164;324;93;164;210;378 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. Subsequently, M184V develops because of an independent substitution within the same triplet codon (ATG to GTG), and viruses containing M184V then outcompete those containing M184I because of superior replication fitness. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV M184I;M184V;M184V 174;14;135 179;19;140 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. The basis for the emergence of resistance with rilpivirine seems to be that both the M184V and M184I mutations can impair HIV replicative fitness, with M184I usually arising first, because it derives from a G to A (ATG to ATA) hypermutation. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV M184I;M184I;M184V 95;152;85 100;157;90 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. The number of virologic failures after 192 weeks remained low, ie, 11% of patients in the rilpivirine group and 9% in the efavirenz arm (P = 0.7), and the M184V mutation associated with resistance to lamivudine and emtricitabine was not present in any of the efavirenz patients but was found in 33% of patients in the rilpivirine failure group. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV M184V 155 160 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. These findings also explain the higher levels of treatment failure among rilpivirine-treated patients in the ECHO and THRIVE clinical trials, although other work suggests that viruses containing both the E138K and M184I viruses do not have high replicative fitness. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV E138K;M184I 204;214 209;219 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. Virologic failure due to resistance was rare in the C204 dose-ranging study referred to above (ie, 6% of rilpivirine-treated patients versus 7% of efavirenz-treated patients), and the proportion of individuals with treatment-emergent non-nucleoside reverse transcriptase inhibitor mutations was similar (ie, 53% and 50% in the rilpivirine and efavirenz arms, respectively) among failures in the two study arms, with E138K and K103N being the most common mutations. 2013 HIV/AIDS (Auckland, N.Z.) Introduction HIV E138K;K103N 416;426 421;431 NNRTI 234 270 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. However, in vitro drug selection experiments performed in our laboratory have identified a R263K mutation within the integrase coding region as a resistance mutation when subtype B viruses were cultivated in the presence of DTG and also showed that H51Y commonly emerged as a secondary mutation . 2013 Retrovirology Introduction HIV H51Y;R263K 249;91 253;96 IN 117 126 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In addition, H51Y was detected in highly treatment-experienced patients failing EVG-containing regimens . 2013 Retrovirology Introduction HIV H51Y 13 17 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In contrast, H51Y on its own did not affect any of these various activities. 2013 Retrovirology Introduction HIV H51Y 13 17 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In view of the possibility that H51Y and R263K may define a unique resistance pathway against DTG, our results provide an explanation for the absence of drug resistance mutations in drug-naive patients who have been treated with DTG. 2013 Retrovirology Introduction HIV H51Y;R263K 32;41 36;46 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. We show here that the H51Y mutation in combination with R263K increased resistance to DTG, over that conferred by R263K alone, and was accompanied by a dramatic decrease in integrase strand transfer enzymatic activity, viral replicative fitness, and the ability of HIV DNA to integrate into host cell genomes. 2013 Retrovirology Introduction HIV H51Y;R263K;R263K 22;56;114 26;61;119 IN 173 182 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In addition, other mutants such as M230I and M230L were prone to introduce tandem repeat deletions, particularly in the presence of biased dNTP concentrations. 2013 Nucleic acids research Introduction HIV M230I;M230L 35;45 40;50 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In previous studies, we demonstrated that substituting Ile for Val75 in HIV-1 group O and group M RTs increased their fidelity around 2-fold, as determined with an M13mp2 lacZalpha-based forward mutation assay. 2013 Nucleic acids research Introduction HIV V75I 55 68 RT 98 101 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In some cases, amino acid substitutions at those positions could affect slippage of the template or primer strands and result in altered frameshift error rates, as observed with mutants E89G, G262A or W266A. 2013 Nucleic acids research Introduction HIV E89G;G262A;W266A 186;192;201 190;197;206 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Modest reductions in accuracy were also observed with MLV vectors carrying other RNase H primer grip mutations such as S557A, A558V and Q559L. 2013 Nucleic acids research Introduction HIV A558V;Q559L;S557A 126;136;119 131;141;124 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. One round of replication experiments carried out ex vivo showed that the primer grip mutation Y501W produces a 4-fold increase in mutant frequency compared with the wild-type HIV-1 RT, although another mutation in the same region (I505A) had no effect on the mutation rate. 2013 Nucleic acids research Introduction HIV I505A;Y501W 231;94 236;99 RT 181 183 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Overall error rates of 1.4 x 10-4, 5.5 x 10-5 and 2.9 x 10-5 were obtained for wild-type BH10 (BH10_WT), O_WT and mutant O_V75I RTs, respectively. 2013 Nucleic acids research Introduction HIV V75I 123 127 RT 128 131 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Sequence analysis of progeny virus revealed that mutations induced by Y586F were frequently observed at adenine-thymine tracts. 2013 Nucleic acids research Introduction HIV Y586F 70 75 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Here we investigate the extent and mechanism of resistance of the HIV-1 CA mutant V86M to R332G-R335G TRIM5alphahu and other mutants of the v1 domain. 2013 Retrovirology Introduction HIV R332G;R335G;V86M 90;96;82 95;101;86 Capsid 72 74 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The mechanism of HIV-1 resistance to TRIM5alpharh conferred by V86M CA was not addressed in this study. 2013 Retrovirology Introduction HIV V86M 63 67 Capsid 68 70 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The mutation V86M in the CypA-binding loop of HIV-1 CA has been identified as conferring partial resistance to TRIM5alpharh. 2013 Retrovirology Introduction HIV V86M 13 17 Capsid 52 54 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. All of them showed a conserved S61A substitution that led to enhanced intracellular stability and higher virus release activity. 2013 PloS one Introduction HIV S61A 31 35 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. D30N occurs specifically in response to nelfinavir treatment, whereas M36I and A71V, along with other non-active site substitutions, appear as a result of selective pressure of treatments using various protease inhibitors. 2013 Biochemistry Introduction HIV A71V;M36I;D30N 79;70;0 83;74;4 PR 202 210 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. In particular, SDSL-DEER was used to understand the effects of the accumulation of primary, D30N, and secondary mutations M36I and A71V on the flap conformational sampling of WT subtype B HIV-1 PR. 2013 Biochemistry Introduction HIV A71V;D30N;M36I 131;92;122 135;96;126 PR 194 196 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Specifically, a site-specific cysteine residue is incorporated into the aqueous solvent-exposed flap sites (e.g., K55C and K55C') for chemical modification with an EPR-active spin probe (Figure 1B), where inter-spin distance in the 20-60 A range can readily be studied by DEER. 2013 Biochemistry Introduction HIV K55C;K55C 123;114 127;118 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Recently, we characterized a clinically derived HIV-1 protease (PR20) bearing 20 mutations [Q7K, L10F, I13V, I15V, D30N, V32I, L33F, E35D, M36I, S37N, I47V, I54L, Q58E, I62V, L63P, A71V, I84V, N88D, L89T and L90M] and extremely resistant to all clinical protease inhibitors (PIs). 2013 Journal of medicinal chemistry Introduction HIV A71V;D30N;E35D;I13V;I15V;I47V;I54L;I62V;I84V;L10F;L33F;L63P;L89T;L90M;M36I;N88D;Q58E;Q7K;S37N;V32I 181;115;133;103;109;151;157;169;187;97;127;175;199;208;139;193;163;92;145;121 185;119;137;107;113;155;161;173;191;101;131;179;203;212;143;197;167;95;149;125 PR;PR;PI;PR 54;254;275;64 62;262;278;66 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Forced viral evolution was used to examine how the gp120-gp41 complex adapts to overcome a mutation (K601D in the DSR) that causes defective gp120-gp41 association. 2013 PLoS pathogens Introduction HIV K601D 101 107 gp120;gp120;gp41;gp41 51;141;57;147 56;146;61;151 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The defective phenotype was restored by second site mutations leading to the loss of PNGSs at V1 positions 136 and 142, the former operating in conjunction with L494I in C5 of gp120 and the latter requiring D601N in the DSR. 2013 PLoS pathogens Introduction HIV D601N;L494I 207;161 212;166 gp120 176 181 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Surprisingly, inactivation of Vpu significantly increased the infectious capability of Gag mutant (L30E) viruses by augmenting Env incorporation. 2013 PloS one Introduction HIV L30E 99 103 Vpu;Env;Gag 30;127;87 33;130;90 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. We have examined whether Vpu plays any role in the MA-Env cross-talk, especially in context with Gag MA L30E mutation which is known to diminish Env association with detergent resistant membranes (DRM), incorporation into virions and infectivity. 2013 PloS one Introduction HIV L30E 104 108 Vpu;Env;Env;Gag;Matrix;Matrix 25;54;145;97;51;101 28;57;148;100;53;103 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. A D601H pseudoreversion in the DSR operated in conjunction with D674E in the MPER to improve gp120-gp41 association and to enable efficient viral spread in culture. 2013 Retrovirology Introduction HIV D601H;D674E 2;64 7;69 gp120;gp41 93;99 98;103 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The revertant W596L/K601H (WL/KH) and W596L/K61H/D674E (WL/KH/DE) viruses exhibited increased sensitivity to the broadly neutralizing MPER-directed MAbs 2F5 and 4E10. 2013 Retrovirology Introduction HIV D674E;K61H;W596L;K601H;W596L 49;44;38;20;14 54;48;43;25;19 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. To this end, we forced the evolution of a DSR mutant virus with disrupted gp120 association, HIV-1AD8-W596L/K601D (WL/KD), by sequential passage in U87.CD4.CCR5 cells. 2013 Retrovirology Introduction HIV K601D;W596L 108;102 113;107 gp120 74 79 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Randomized controlled trials have shown that the key substitutions in patients failing atazanavir-containing regimens are I50L and N88S. 2013 The Journal of antimicrobial chemotherapy Introduction HIV I50L;N88S 122;131 126;135 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. Binding orientations and favorable interactions of ligands against the wild-type (WT) and three different mutation strains; Y212R (equivalent to Y143R HIV-1 IN), N224H (equivalent to N155H HIV-1 IN) and S217H (equivalent to G140S/Q148H HIV-1 IN) of PFV IN were predicted. 2013 Bioinformation Introduction HIV G140S;N155H;N224H;Q148H;S217H;Y143R;Y212R 224;183;162;230;203;145;124 229;188;167;235;208;150;129 IN;IN;IN;IN 157;195;242;253 159;197;244;255 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The secondary mutation at position G140 (G140S) combined with primary mutation Q148K/R/H significantly enhanced drug resistance. 2013 Bioinformation Introduction HIV G140S;Q148H;Q148K;Q148R 41;79;79;79 46;88;88;88 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The two primary resistance pathways involved mutations of the amino acids at Q148 (Q148K/R/H) or N155 (N155/H) whereas a third primary mutation pathway at Y143 (Y143C/R) was less commonly found . 2013 Bioinformation Introduction HIV Q148H;Q148K;Q148R;Y143C;Y143R 83;83;83;161;161 92;92;92;168;168 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. A recent study conducted in Durban, South Africa reported that among 33 patients with virologic failure while receiving a TDF-containing ART regimen, 23 (70%) had the K65R mutation, suggesting an unusually high prevalence of TDF resistance at treatment failure. 2013 Antiviral therapy Introduction HIV K65R 167 171 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Furthermore, use of stavudine (d4T) selects for the K65R mutation in a higher proportion of patients with subtype C HIV than may have been expected from the subtype B experience. 2013 Antiviral therapy Introduction HIV K65R 52 56 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. However, knowledge related to K65R development during treatment with TDF remains limited in settings in which subtype C HIV predominate and results differ widely . 2013 Antiviral therapy Introduction HIV K65R 30 34 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. In addition, it is unclear whether there are specific risk factors for the K65R development during treatment failure while on TDF. 2013 Antiviral therapy Introduction HIV K65R 75 79 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. In addition, there may be a higher percentage of minority K65R quasi-species among ART-naive individuals infected with subtype C compared to subtype B. 2013 Antiviral therapy Introduction HIV K65R 58 62 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. In order to further examine the selection of K65R in a subtype C population, we described HIV drug resistance, including the prevalence of minority K65R, K70E, and M184V species, and associations with resistance, including prior receipt of either d4T or zidovudine (AZT), among patients at the time of virological failure on a TDF-containing ART regimen. 2013 Antiviral therapy Introduction HIV K65R;K65R;K70E;M184V 45;148;154;164 49;152;158;169 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Subtype C HIV-1, the subtype that predominates in southern Africa and India, has been reported to develop the principle TDF-associated drug resistance mutation, K65R in the HIV reverse transcriptase, more rapidly than other subtypes during in vitro selection. 2013 Antiviral therapy Introduction HIV K65R 161 165 RT 177 198 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. This is in contrast to a report on K65R prevalence at virologic failure from an international collaboration of mostly European cohorts in which the proportion of subtype C HIV with the K65R was 16.2% and a study from multiple African sites in which the prevalence was 27.7%. 2013 Antiviral therapy Introduction HIV K65R;K65R 35;185 39;189 23792096 Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance. Although drug resistance is relatively less likely to develop against LPV compared to other HIV-1 protease inhibitors, resistance mutations, including 32I, 47A, 46I, L33F, I54V, V82A, I84V, and L90M, or combinations among L76V, M46I, and V82A in the protease, and A431V in gag are responsible for reduced efficacy of LPV. 2013 Biochemical and biophysical research communications Introduction HIV A431V;I54V;I84V;L33F;L76V;L90M;M46I;V82A;V82A 264;172;184;166;222;194;228;178;238 269;176;188;170;226;198;232;182;242 PR;PR;Gag 98;250;273 106;258;276 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. An example of this type of resistance is conferred by the M184V mutation, which decreases HIV susceptibility to lamivudine (3TC) and emtricitabine (FTC). 2013 Retrovirology Introduction HIV M184V 58 63 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. In an effort to investigate the effect of EFdA against drug-resistant strains of HIV-1 we found that RT mutation K65R confers hypersusceptibility to EFdA. 2013 Retrovirology Introduction HIV K65R 113 117 RT 101 103 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Recent crystallographic data suggest that the K65R mutation disrupts the interaction between the side chains of 65R and 72R resulting in structural changes that lead to NRTI resistance. 2013 Retrovirology Introduction HIV K65R 46 50 NRTI 169 173 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The excision reaction is facilitated by Excision Enhancement Mutations (EEMs), typically M41L, D67N, K70R, T215Y/F, L210W, and K219E/Q, which are also known as Thymidine Associated Mutations (TAMs) because they were historically linked to resistance to thymidine analogs AZT and d4T. 2013 Retrovirology Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 95;127;127;101;116;89;107;107 99;134;134;105;121;93;114;114 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The K65R mutation in HIV-1 RT is the signature mutation selected during tenofovir-based therapy. 2013 Retrovirology Introduction HIV K65R 4 8 RT 27 29 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Understanding the molecular basis of K65R hypersusceptibility to EFdA may lead to new and more effective combination therapies. 2013 Retrovirology Introduction HIV K65R 37 41 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Viruses carrying K65R have reduced susceptibility to tenofovir and other NRTIs, but remain susceptible to zidovudine (AZT). 2013 Retrovirology Introduction HIV K65R 17 21 NRTI 73 78 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We carried out a series of biochemical experiments to elucidate the mechanism of this phenomenon and we propose here that K65R increases the susceptibility to EFdA mainly by suppressing the ATP- or PPi-dependent repair of EFdA-MP-terminated DNA. 2013 Retrovirology Introduction HIV K65R 122 126 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Surprisingly, the previously identified E45A CA mutant, which exhibits hyperstable cores in vitro, exhibited efficient staining of viral-associated RNA through cores in vitro and accelerated staining kinetics in vivo, suggestive of a permeable capsid. 2013 Retrovirology Introduction HIV E45A 40 44 Capsid;Capsid 244;45 250;47 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. One of these viruses, designated HIV-1V3-M5, contains a set of five mutations I304V/F312W/T314A/E317D/I318V in the V3 loop (from Cys293 to Cys327). 2013 PloS one Introduction HIV E317D;F312W;I304V;I318V;T314A 96;84;78;102;90 101;89;83;107;95 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. The highest mutation frequencies were M184V for RT inhibitor resistance and L63P for PI resistance. 2010 Boletin de la Asociacion Medica de Puerto Rico Introduction HIV L63P;M184V 76;38 80;43 PI;RT 85;48 87;50 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Another PR mutation, L90M, elucidates an HLA-A*02 restricted epitope spanning the PR positions 76-84 by inducing an appropriate proteasomal cleavage site. 2013 PloS one Introduction HIV L90M 21 25 PR;PR 8;82 10;84 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. For example, the HIV-1 protease (PR) resistance mutation M46I is a CTL escape mutation of an HLA-A*02 restricted epitope, but also serves as a resistance mutation to the PIs, tripanavir and atazanavir. 2013 PloS one Introduction HIV M46I 57 61 PR;PI;PR 23;170;33 31;173;35 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Furthermore, using computational tools that predict HLA binding affinity and proteasomal cleavage, a potential causative immunological component was discovered that could possibly drive the diminished frequency of L90M in the B*15, B*48 and A*32 subtypes. 2013 PloS one Introduction HIV L90M 214 218 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Here, it was discovered that there are possible interactions between a common and important protease inhibitor resistance mutation, L90M, and the HLA subtypes B*15, B*48 and potentially A*32. 2013 PloS one Introduction HIV L90M 132 136 PR 92 100 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. In the case of the HLA-B*44 restricted PR 34-42 epitope EEMNLPGRW, the escape mutation PR D35E is predicted by the MHC binding predictor, NetMHCPan, to have a dramatic negative impact on peptide affinity to HLA-B*4402, possibly diminishing the presentation potential of the epitope on HLA-B*4402. 2013 PloS one Introduction HIV D35E 90 94 PR;PR 39;87 41;89 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. This research provide support, at least in principle, that the HLA genotype could provide a protective component and that appropriate protease inhibitors for which L90M is a preferred mutation should be considered in patients matching the HLA subtypes B*15, B*48 and A*32. 2013 PloS one Introduction HIV L90M 164 168 PR 134 142 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Using the aforementioned data correlating relating amino acid substitutions with HLA subtype, patients were assigned HLA subtypes and the frequencies of L90M were compared between sequence sets of patients that are HLA B*15/B*48/A*32 positive and those that are not. 2013 PloS one Introduction HIV L90M 153 157 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. d4T/ddI dual therapy has been associated with the occurrence of Q151M and K65R, as well as young age, low CD4+ T-cell count, high HIV RNA viral load (VL) and experience of more than two ARV regimens before resistance genotyping testing. 2013 PloS one Introduction HIV K65R;Q151M 74;64 78;69 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. K65R confers resistance to stavudine (d4T) and TDF and possibly to lamivudine/emtricitabine (3TC/FTC), didanosine (ddI) and abacavir (ABC), while Insert69 confers resistance to all NRTIs available today. 2013 PloS one Introduction HIV K65R 0 4 NRTI 181 186 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Q151M confers resistance to all NRTIs, except tenofovir (TDF). 2013 PloS one Introduction HIV Q151M 0 5 NRTI 32 37 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Q151M, K65R substitutions, and insertions at codon 69 (Insert69) in the reverse transcriptase encoding region of HIV-1 genome confer resistance to a large range of nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and are thus called multi-nucleos(t)ide resistance (MNR) mutations. 2013 PloS one Introduction HIV K65R;Q151M 7;0 11;5 NRTI;RT;NRTI 164;72;212 199;93;217 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. In a Ugandan study, the K103N mutation was relatively more frequent in C subtype- infected women failing NNRTI-based therapy than in both A and D subtypes. 2013 BMC infectious diseases Introduction HIV K103N 24 29 NNRTI 105 110 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. The G190A/S mutation was considered a common polymorphism in Israeli C subtype patients, but not in Indian C subtype individuals. 2013 BMC infectious diseases Introduction HIV G190A;G190S 4;4 11;11 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Accessory mutations such as L10I, L63P and A71V have been shown to increase the thermal stability and pH tolerance of a drug resistant PR bearing the destabilizing active-site mutation I84V. 2013 Biochemistry Introduction HIV A71V;I84V;L10I;L63P 43;185;28;34 47;189;32;38 PR 135 137 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Next, using differential scanning calorimetry, we investigate several properties relating to the stability of PR20 such as 1) whether the enhanced stability of PR20 relative to PR results from inter-monomer interactions or a more stable monomer fold, 2) if specific mutations L33F and L63P at sites of autoproteolysis selected under drug pressure in PR20 affect both autoproteolysis and stability and 3) whether an entropically stabilized PR dimer as a single-chain construct influences binding affinity to inhibitors. 2013 Biochemistry Introduction HIV L33F;L63P 276;285 280;289 PR;PR;PR;PR;PR 110;160;177;350;439 112;162;179;352;441 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. These include ANAM-11, which bears 11 mutations including L63P, and mutant I50L/A71V showing Tm increases of 4.8 C and ~2 C, respectively, relative to wild type. 2013 Biochemistry Introduction HIV A71V;I50L;L63P 80;75;58 84;79;62 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. Importantly, non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance mutations (mainly K103N) were not found in the first study but were detected in the last two studies. 2013 Journal of the International AIDS Society Introduction HIV K103N 98 103 NNRTI;NNRTI 13;62 49;67 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. In addition, in the ART-experienced, INSTI-naive SAILING study, 16 patients in the RAL group had typical treatment-emergent RAL resistance with high fold-changes to RAL, and 2 patients receiving DTG developed the IN substitution R263K, which conferred fold-changes of <2. 2013 PloS one Introduction HIV R263K 229 234 INSTI;IN 37;213 42;215 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. In our efforts to structurally rationalize DTG's distinct resistance and dissociation kinetics profiles, we constructed wild-type, Q148R, Q148K, Q148H/G140S and N155H HIV-1 IN models in complex with U5 LTR DNA using carefully selected structural data from wild-type and mutant PFV intasomes as well as Tn5 transposase to model key missing active-site elements from a selected structure of the HIV-1 IN catalytic core. 2013 PloS one Introduction HIV G140S;N155H;Q148H;Q148K;Q148R 151;161;145;138;131 156;166;150;143;136 LTR;IN;IN 202;173;399 205;175;401 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Indeed, DTG's antiviral activity against the single IN mutants mentioned remains comparable to its activity against wild-type HIV-1 and has only a 2.6-fold increase in resistance against the Q148H/G140S IN mutant virus compared with >130- and >890-fold increases for RAL and EVG, respectively. 2013 PloS one Introduction HIV G140S;Q148H 197;191 202;196 IN;IN 52;203 54;205 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Owing to the work of Hare et al, crystal structures of the wild-type, S217H and N224H prototype foamy virus (PFV) intasomes are now available, and many of these are in complex with 1 of several IN inhibitors, including DTG, RAL and EVG, providing the first molecular views into the likely architecture of the HIV-1 IN catalytic site when bound to viral DNA and inhibitor. 2013 PloS one Introduction HIV N224H;S217H 80;70 85;75 IN;IN 194;315 196;317 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. Unlike most PI drugs, resistance to the NNRTIs nevirapine and efavirenz requires only a single mutation at the K103N codon and even a single dose of NNRTI monotherapy can result in resistance. 2013 PloS one Introduction HIV K103N 111 116 NNRTI;NNRTI;PI 40;149;12 46;154;14 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. For example, issues with efavirenz include its daily dosage of 600 mg, poor activity towards HIV-1 variants containing the commonly occurring Lys103Asn (K103N) mutation in RT, and neurological side effects. 2013 Journal of the American Chemical Society Introduction HIV K103N;K103N 142;153 151;158 RT 172 174 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. The difluoro analog 4 is also extremely potent at 0.32 nM, has good potency towards variant strains containing the Y181C (16 nM) and K103N/Y181C (85 nM) mutations, and shows low cytotoxicity towards the T-cells (CC50 = 45 microM). 2013 Journal of the American Chemical Society Introduction HIV K103N;Y181C;Y181C 133;115;139 138;120;144 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Also, the N348I/T369I combination reduces the susceptibility of NNRTIs, and reduces replication capacity of RT. 2014 Proteins Introduction HIV N348I;T369I 10;16 15;21 NNRTI;RT 64;108 70;110 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Here, we report an MD study of RT-DNA, RT-DNA-nevirapine(NVP), and N348I/T369I mutant RT-DNA-NVP complexes. 2014 Proteins Introduction HIV N348I;T369I 67;73 72;78 RT;RT;RT 31;39;86 33;41;88 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The connection mutations N348I or T369I in combination with primary EEMs or NNRTI-resistance mutations enhance NRTI or NNRTI resistance, respectively. 2014 Proteins Introduction HIV N348I;T369I 25;34 30;39 NNRTI;NNRTI;NRTI 76;119;111 81;124;115 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Therefore, understanding of (i) the overall structural consequence of the connection mutations N348I and T369I on RT, and (ii) how these spatially distant mutations trigger NNRTI and NRTI resistance have important functional implications. 2014 Proteins Introduction HIV N348I;T369I 95;105 100;110 NNRTI;NRTI;RT 173;183;114 178;187;116 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. At a very early phase of primary HIV-1 infection, a Tyr-to-Phe mutation at the 2nd position of the Nef134-10 epitope (Y135F; Nef134-10(2F)) is frequently selected. 2013 Scientific reports Introduction HIV Y135F 118 123 Nef;Nef 99;125 102;128 HIV infections 33 48 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. In the small number of patients without Y135F mutation, F139L mutation was selected. 2013 Scientific reports Introduction HIV F139L;Y135F 56;40 61;45 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Since a wild type specific TCR showed a substantial affinity to the epitope with F139L mutation (Nef134-10(6L)), we also solved the crystal structure of the pHLA/TCR interaction between them. 2013 Scientific reports Introduction HIV F139L 81 86 Nef 97 100 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. Consistently, double mutation of P90A and RT D185E, but not IN D116N, suppressed IP10 induction. 2013 Nature Introduction HIV D116N;D185E;P90A 63;45;33 68;50;37 IN;RT 60;42 62;44 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. Given that CA mutation N74D prevents recruitment of CPSF6 we hypothesized that CPSF6 depletion would induce WT HIV-1 to trigger IFN responses in MDM. 2013 Nature Introduction HIV N74D 23 27 Capsid 11 13 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. HIV-1 capsid (CA) mutant N74D cannot recruit CPSF6 and is insensitive to depletion of HIV-1 cofactors Nup358 and TNPO3 suggesting it may utilize alternate cofactors for nuclear entry. 2013 Nature Introduction HIV N74D 25 29 Capsid;Capsid 6;14 12;16 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. Infection by HIV-1 CA N74D, RT D185E double mutant did not stimulate IP-10 expression whereas infection with HIV-1 double mutant CA N74D, IN D116N induced IP10 expression comparable to the WT virus. 2013 Nature Introduction HIV D116N;D185E;N74D;N74D 141;31;22;132 146;36;26;136 IN;Capsid;Capsid;RT 138;19;129;28 140;21;131;30 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. Intriguingly, both N74D and P90A CA mutants replicated in indicator cell lines GHOST and HeLa TZM-bl to WT levels (Extended Data. 2013 Nature Introduction HIV N74D;P90A 19;28 23;32 Capsid 33 35 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. Our data suggest that DNA synthesized by HIV-1 mutants is insensitive to TREX1 degradation, either through nature or location, and in the case of HIV-1 CA P90A, is detected by cGAS leading to cGAMP production. 2013 Nature Introduction HIV P90A 155 159 Capsid 152 154 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. Since HIV-1 N74D is unable to appropriately utilize nuclear pore components and has retargeted integration properties, we hypothesized that the HIV-1 CA mutant P90A, which fails to interact with the cyclophilins CypA and nuclear pore component Nup358, and also has retargeted integration, might also trigger innate sensors. 2013 Nature Introduction HIV P90A 160 164 Capsid 150 152 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. This possibility is consistent with the different integration site targeting preferences of the two mutants with HIV-1 N74D and P90A integrating into lower gene density or higher gene density regions of chromatin respectively, as compared to wild type virus. 2013 Nature Introduction HIV P90A 128 132 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. We find MDM infection by HIV-1 N74D, P90A or WT were equally increased by SIVmac VLP encoding Vpx, suggesting that mutant viruses were not specifically Vpx sensitive (Extended Data. 2013 Nature Introduction HIV P90A 37 41 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. We hypothesise that viral DNA produced by reverse transcription is the target for innate sensing of both HIV-1 CA mutants N74D and P90A in MDM. 2013 Nature Introduction HIV N74D;P90A 122;131 126;135 RT;Capsid 42;111 63;113 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. We used a biological assay to test for cGAMP production in MDM infected by HIV-1 N74D and P90A. 2013 Nature Introduction HIV P90A 90 94 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. Both CD4 independence and neutralization sensitivity were conferred by D470N/E84K mutations in Env that arose in these animals, indicating that these are linked phenotypes resulting from a common structural basis. 2013 Retrovirology Introduction HIV D470N;E84K 71;77 76;81 Env 95 98 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In this report, we confirm that the S40F mutation results in defects in particle maturation. 2013 Retrovirology Introduction HIV S40F 36 40 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Notwithstanding, it was recently reported that the substitution of F for S at residue 40, a mutation that does not alter the sequence of the overlapping pol frame where the viral PR is encoded, results in a loss of infectivity due to inefficient cleavage at the capsid-spacer p1 (CA-SP1) junction. 2013 Retrovirology Introduction HIV S40F 67 88 Capsid;Pol;SP1;Capsid;PR 262;153;283;280;179 268;156;286;282;181 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. When Tsg101-PTAP interaction is disrupted, e.g., in the Gag mutant (P7L) where Leu has been substituted for Pro7, budding becomes dependent on L domain-2 in p6 (LY36PX2S40L; where X are highly, but not absolutely, conserved amino acids. 2013 Retrovirology Introduction HIV L7P;P7L 79;68 112;71 Gag;Gag 56;157 59;159 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. Our data demonstrate that RV by itself has activity against viruses with the M184V mutation, unlike what has been shown with wild type HIV-1 or with HIV-1 carrying thymidine/adenosine analog resistance mutations. 2014 AIDS (London, England) Introduction HIV M184V 77 82 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. The cytosine analogs lamivudine (3TC) and emtricitabine (FTC) select for the M184V mutation, which confers high-level drug resistance (100 to 1000-fold). 2014 AIDS (London, England) Introduction HIV M184V 77 82 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. Thus, we tested the hypothesis that reduction of dNTP levels with RV might impair the replication of HIV-1 carrying the M184V mutation. 2014 AIDS (London, England) Introduction HIV M184V 120 125 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Additional mutations within or flanking the TW10 epitope can have a compensatory effect and partially restore the fitness cost associated with the T242N mutation. 2013 PloS one Introduction HIV T242N 147 152 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Furthermore, an association between disease progression and the presence of 2 or more of the compensatory mutations H219Q, I223V, M228I, N252H and G248X was observed. 2013 PloS one Introduction HIV G248X;H219Q;I223V;M228I;N252H 147;116;123;130;137 152;121;128;135;142 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. The T242N escape mutation in the HLA-B*57/58:01 restricted TW10 epitope in Gag impairs viral replication, which can explain the protective effect of this HLA type even after escape from CTL responses has occurred. 2013 PloS one Introduction HIV T242N 4 9 Gag 75 78 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. For PR:substrate coevolution in LP1'Fp1-p6D30N/N88D or SP3Np1-p6D30N/N88D variants, however, no experimentally determined structures have been reported so far. 2012 Journal of chemical theory and computation Introduction HIV D30N;D30N;N88D;N88D 42;64;69;47 46;68;73;51 Gag;Gag;PR 40;62;4 42;64;6 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In the NC-p1 cleavage site, Ala in the P2 position mutates to a Val in response to the V82A multidrug-resistance PR mutation (AP2VNC-p1V82A). 2012 Journal of chemical theory and computation Introduction HIV V82A;V82A 135;87 139;91 NC;PR 7;113 9;115 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. Replicative capacity assays showed that the D30N/N88D viruses with the compensatory mutations in p1-p6 do not have improved fitness relative to viruses with mutations in the PR alone. 2012 Journal of chemical theory and computation Introduction HIV D30N;N88D 44;49 48;53 Gag;PR 100;174 102;176 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The p1-p6 cleavage site mutates predominantly at the P1' or P3' positions associated with the PR double mutation D30N/N88D (LP1'Fp1-p6D30N/N88D and SP3'Np1-p6D30N/N88D), which is a signature of nelfinavir treatment. 2012 Journal of chemical theory and computation Introduction HIV D30N;D30N;D30N;N88D;N88D;N88D 134;158;113;139;163;118 138;162;117;143;167;122 Gag;Gag;Gag;PR 7;132;156;94 9;134;158;96 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The structural basis for PR-substrate coevolution in AP2VNC-p1V82A variant came from analyzing the crystal structures of inactive D25N WT (WT) and V82A HIV-1 PR in complex with their respective WT and AP2V mutant NC-p1 substrates. 2012 Journal of chemical theory and computation Introduction HIV V82A;D25N;V82A 62;130;147 66;134;151 NC;PR;PR 213;25;158 215;27;160 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. V82A virus has an even lower replicative capacity in combination with mutations at Gag 431, which corresponds to Ala-P2 of NC-p1 cleavage site, compared to those without this mutation. 2012 Journal of chemical theory and computation Introduction HIV V82A 0 4 Gag;NC 83;123 86;125 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Interestingly, Vif mutants that do not bind Cul5, including Vif His108Ala, are structurally different from Vif wild-type and mutants that do bind Cul5. 2014 Retrovirology Introduction HIV H108A 64 73 Vif;Vif;Vif 15;60;107 18;63;110 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. As a result, it is reasonable to speculate that the presence of M50I could compromise DTG activity in INSTI-naive patients as well as contribute to cross-resistance in treatment-experienced patients. 2014 Retrovirology Introduction HIV M50I 64 68 INSTI 102 107 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. As such, tissue culture selection studies with this drug have revealed the emergence of the R263K mutation in the integrase of HIV subtypes B and circulating recombinant form CRF02_A/G viruses . 2014 Retrovirology Introduction HIV R263K 92 97 IN 114 123 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Here, we present the biochemical characterization of the M50I substitution alone and in combination with the primary resistance mutation R263K in subtype B integrase. 2014 Retrovirology Introduction HIV M50I;R263K 57;137 61;142 IN 156 165 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. However, the R263K mutation has been found in INSTI-naive ART-experienced patients receiving DTG treatment who have failed therapy with this drug . 2014 Retrovirology Introduction HIV R263K 13 18 INSTI 46 51 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In addition, this polymorphism has been observed in combination with R263K in a patient who subsequently failed treatment with RAL . 2014 Retrovirology Introduction HIV R263K 69 74 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In previous studies, the M50I polymorphism has been found in 10-25% of INSTI-naive patients . 2014 Retrovirology Introduction HIV M50I 25 29 INSTI 71 76 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Our results demonstrate that the M50I polymorphism does not restore the loss in HIV-1 infectivity associated with R263K and confers moderate resistance to DTG when combined with the latter resistance mutation. 2014 Retrovirology Introduction HIV M50I;R263K 33;114 37;119 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. R263K has been shown to confer low levels of resistance to DTG while decreasing viral fitness . 2014 Retrovirology Introduction HIV R263K 0 5 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The same selection study also revealed multiple secondary mutations including the M50I polymorphism in subtype B integrase . 2014 Retrovirology Introduction HIV M50I 82 86 IN 113 122 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. The most common resistance profiles identified include the M184V mutation (associated with nucleoside reverse transcriptase inhibitors; NRTIs), followed by the K103N mutation (associated with non-nucleoside reverse transcriptase inhibitors; NNRTIs). 2014 AIDS research and therapy Introduction HIV K103N;M184V 160;59 165;64 NNRTI;NRTI;NNRTI;NRTI 192;91;241;136 228;123;247;141 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. Thymidine analogue mutations (TAMs) and the K65R mutation were less common. 2014 AIDS research and therapy Introduction HIV K65R 44 48 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. HIV-1 viruses bearing either the A92E or G94D CA mutation are defective for replication in HeLa or H9 T cells, but disruption of the CypA-CA interaction rescued infectivity of these mutants in these cells. 2014 Retrovirology Introduction HIV A92E;G94D 33;41 37;45 Capsid;Capsid 46;138 48;140 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. How CypA promotes HIV-1 infection or contributes to the block to A92E or G94D mutant virus replication in certain cell lines is not well understood. 2014 Retrovirology Introduction HIV A92E;G94D 65;73 69;77 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In addition, N74D and A105T render WT HIV-1 dependent on CypA-CA binding in H9 and HeLa cells, host cells that do not otherwise require CypA for WT HIV-1 replication. 2014 Retrovirology Introduction HIV A105T;N74D 22;13 27;17 Capsid 62 64 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Interestingly, CA mutations N74D and A105T have no effect on the CA-CypA interaction, but, when encoded in cis, either mutant will rescue the infectivity defect of the A92E mutant. 2014 Retrovirology Introduction HIV A105T;A92E;N74D 37;168;28 42;172;32 Capsid;Capsid 15;65 17;67 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. More specifically, it is not clear at which step of HIV-1 replication CypA inhibits A92E and G94D mutant viruses. 2014 Retrovirology Introduction HIV A92E;G94D 84;93 88;97 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Serial passage of HIV-1 in CD4+-HeLa cells, in the presence of a competitive inhibitor of the CA-CypA interaction, selected for HIV-1 CA mutants A92E and G94D. 2014 Retrovirology Introduction HIV A92E;G94D 145;154 149;158 Capsid;Capsid 94;134 96;136 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The relevance of the CA-CypA interaction for HIV-1 replication has been demonstrated using multiple experimental approaches, including disruption of binding with the competitive inhibitor cyclosporine A (CsA), CA mutants G89V and P90A, CypA mutants in the active site, and depletion of endogenous CypA by gene knock-out or RNA knock-down. 2014 Retrovirology Introduction HIV G89V;P90A 221;230 225;234 Capsid;Capsid 21;210 23;212 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. When infecting 293 T, HOS, TE671, or Jurkat T cells, A92E and G94D render HIV-1 replication independent of CypA. 2014 Retrovirology Introduction HIV A92E;G94D 53;62 57;66 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Certain HIV-1 viral capsid mutants, such as N74D, were not impaired by Nup358 knockdown in HeLa cells and interact poorly with Nup358Cyp in vitro; however they remained puzzlingly sensitive to TRIM-Nup358Cyp. 2014 PLoS pathogens Introduction HIV N74D 44 48 Capsid 20 26 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Cyclosporine (Cs) treatment or certain mutations in the cyclophilin binding loop of HIV-1 capsid (e.g., G89V), both of which abrogate CypA binding, impair HIV-1 infectivity. 2014 PLoS pathogens Introduction HIV G89V 104 108 Capsid 90 96 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. In CypA knockout (PPIA -/-) Jurkat CD4+ human T cells, wild type HIV-1 and G89V viruses are equally impaired and Cs does not have additive effect, which suggested that among the sixteen human cyclophilin domain-containing proteins, only CypA has a functionally relevant interaction with the HIV-1 capsid. 2014 PLoS pathogens Introduction HIV G89V 75 79 Capsid 297 303 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. By contrast, the major T-20 resistance mutations were not detected in the gp41 HR1 region, and the S138A substitution combined with mutations in the HR1 region was not detected in the HR2 regions of the Korean HIV isolates (Table 2). 2014 Journal of Korean medical science Introduction HIV S138A 99 104 gp41 74 78 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. In addition, many of the FPs in Korean HIV-1 isolates had L7M substitutions near the FLGFL motif. 2014 Journal of Korean medical science Introduction HIV L7M 58 61 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. In addition, minor mutations associated with reduced susceptibility to T-20 have been reported in several countries as follows: N42S (23%), L44M (2.5%), G36S (0.5%), and S138A (4%) in Spain; N43K (1.8%), L44M (2.5%), E137K (10%), and S138A (2.5%) in Brazil; N42S (16.4%) and E137K (25%) in Italy; and L44M (1.7%), N42S (16%), E137K (15.4%), S138A (8.6%), N42S/S137A (0.5%), and N42S/L44M/E137K (0.5%) in the USA. 2014 Journal of Korean medical science Introduction HIV E137K;L44M;N42S;E137K;E137K;E137K;G36S;L44M;L44M;L44M;N42S;N42S;N42S;N42S;N43K;S137A;S138A;S138A;S138A 388;383;378;217;275;326;153;140;204;301;128;258;314;355;191;360;170;234;341 393;387;382;222;280;331;157;144;208;305;132;262;318;359;195;365;175;239;346 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. In our study, the naturally acquired T-20 resistance mutation was L45M substitutions (n=2, 1.2%); and the N42S substitution (n=21, 12.9%) associated with enhanced T-20 susceptibility was more frequently detected in the HR1 region of HIV-1 gp41 from 163 naive HIV-1 isolates. 2014 Journal of Korean medical science Introduction HIV L45M;N42S 66;106 70;110 gp41 239 243 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. Recent studies have shown that mutations with a polar residue inserted into this motif, such as V2E and L9R substitutions, reduced its fusogenic activity significantly. 2014 Journal of Korean medical science Introduction HIV L9R;V2E 104;96 107;99 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. Recently, it has also been reported that T-20 resistance is greatly increased by a combined mutation of HR1 with secondary and/or compensatory mutations in the HR2 region (N126K, E137K, S138A). 2014 Journal of Korean medical science Introduction HIV E137K;N126K;S138A 179;172;186 184;177;191 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. Several mutations (N126K, E137K, and S138A) in the HR2 domain contributed to enhanced viral fusion activity and reduced the susceptibility to T-20. 2014 Journal of Korean medical science Introduction HIV E137K;N126K;S138A 26;19;37 31;24;42 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. T-20 can restrict HIV-1 replication in an efficient manner, but several T-20 resistance mutations have been reported in HR1 as follows: G36D/S, I37V, V38A/M/E, Q39R, Q40H, N42S/T/D/E, N43D/K/S, L44M, L45M, G36S/L44M, G36S/V38M, V38A/N42D, V38A/N42T, V38E/N42S, N42T/N43S and N42T/N43K. 2014 Journal of Korean medical science Introduction HIV G36D;G36S;G36S;G36S;I37V;L44M;L44M;L45M;N42D;N42D;N42E;N42S;N42S;N42T;N42T;N42T;N42T;N43D;N43K;N43K;N43S;N43S;Q39R;Q40H;V38A;V38A;V38A;V38E;V38E;V38M;V38M 136;136;206;217;144;194;211;200;172;233;172;172;255;172;244;261;275;184;184;280;184;266;160;166;150;228;239;150;250;150;222 142;142;210;221;148;198;215;204;182;237;182;182;259;182;248;265;279;192;192;284;192;270;164;170;158;232;243;158;254;158;226 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. Table 1 shows that the dominant mutation was a T-insertion mutation (n=122, 74.8%), while an L7M substitution near the FLGFL motif was also frequent in HIV-1-infected patients (n=139, 85.3%). 2014 Journal of Korean medical science Introduction HIV L7M 93 96 HIV infections 152 166 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. The minor T-20 resistance mutations detected in the gp41 HR2 region were N126K (1.2%) and E137K (6.7%) in the HIV-1 B subtype only. 2014 Journal of Korean medical science Introduction HIV E137K;N126K 90;73 95;78 gp41 52 56 24616600 Characterization of Gp41 polymorphisms in the fusion peptide domain and T-20 (Enfuvirtide) resistance-associated regions in Korean HIV-1 isolates. The N42S mutation has been detected more frequently in subtype non-B isolates than subtype B isolates (73.3% vs 6.8%; P< 0.001), whereas the L45M mutation has been detected only rarely in subtype B isolates (1.2%). 2014 Journal of Korean medical science Introduction HIV L45M;N42S 141;4 145;8 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. In the present study, we sought to identify a cell-specific host factor that restricts this class of mutants in a CypA-dependent manner, using A92E as a representative example. 2014 PloS one Introduction HIV A92E 143 147 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Passage of HIV-1 in HeLa-CD4+ cells in the presence of CsA led to selection of CsA-resistant CA mutants A92E and G94D. 2014 PloS one Introduction HIV A92E;G94D 104;113 108;117 Capsid 93 95 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. We did not identify a gene responsible for reduced infectivity of A92E mutant in non-permissive cell lines. 2014 PloS one Introduction HIV A92E 66 70 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. We selected 26 genes with at least 3-fold higher expression in non-permissive cell lines, knocked them down individually in a non-permissive cell line, and analyzed the effects on CsA-dependent infection by HIV-1-A92E. 2014 PloS one Introduction HIV A92E 213 217 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. As in HIV-1 the association T97A/Y143C does not confer resistance to DTG, extreme caution must be taken when extrapolating HIV-1 knowledge to HIV-2. 2014 PloS one Introduction HIV T97A;Y143C 28;33 32;38 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Corroborating this is the fact that, at this time, it is still unknown whether the combination H51Y/R263K, that confers some level of resistance to DTG in HIV-1, could be relevant as a mutational pathway leading to HIV-2 resistance. 2014 PloS one Introduction HIV H51Y;R263K 95;100 99;105 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Information on its efficiency against HIV-2 strains bearing integrase inhibitor resistance mutations is still limited, but phenotypic assays carried out with HIV-2 clinical isolates from patients treated with RAL showed that mutations T97A/Y143C, G140S/Q148R or G140T/Q148R/N155H conferred moderate resistance to DTG (7-18-fold increase of the EC50). 2014 PloS one Introduction HIV G140T;N155H;Q148R;G140S;Q148R;T97A;Y143C 262;274;268;247;253;235;240 267;279;273;252;258;239;245 IN 60 69 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. On the other hand, the N155H-Y143C and N155H-Q148R replacements seem to define mutually exclusive pathways to RAL resistance in HIV-2. 2014 PloS one Introduction HIV N155H;N155H;Q148R;Y143C 23;39;45;29 28;44;50;34 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Overall, three major resistance pathways have been identified and shown to elicit high-level raltegravir and elvitegravir resistance in HIV-2: i) N155H/E92Q, ii) Q148R/G140S, and iii) Y143C/E92Q or Y143C/T97A. 2014 PloS one Introduction HIV E92Q;E92Q;G140S;N155H;Q148R;T97A;Y143C;Y143C 152;190;168;144;160;204;182;198 156;194;173;151;167;208;189;203 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. The specific amino acid changes that are known to confer RAL resistance in HIV-1 have also been shown to develop in RAL-treated HIV-2 patients: N155H, Q148K/R and, to a lesser extent, Y143C. 2014 PloS one Introduction HIV N155H;Q148K;Q148R;Y143C 144;151;151;184 149;158;158;189 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. In order to further investigate the molecular mechanisms of high-level resistance, we have determined the crystal structures of PRP51 bearing the inactivating mutation D25N (PRP51-D25N) to abolish self-degradation (autoproteolysis) for sample handing during crystallization. 2014 ACS chemical biology Introduction HIV D25N;D25N 168;180 172;184 PR;PR 128;174 130;176 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Two structures were obtained for PRP51-D25N: a DRV-bound structure (PRP51-D25N/DRV) and a ligand-free structure (PRP51-D25N). 2014 ACS chemical biology Introduction HIV D25N;D25N;D25N 39;74;119 43;78;123 PR;PR;PR 33;68;113 35;70;115 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. When the D25N mutation was introduced into wild-type PR, the affinity for DRV was decreased by about 106-fold, while no substantial changes were observed in the crystal structures. 2014 ACS chemical biology Introduction HIV D25N 9 13 PR 53 55 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. In rhesus macaque studies investigating oral FTC/TDF PrEP, breakthrough infections following rectal exposure showed FTC-selected DR mutations M184V/I. 2014 The Journal of infectious diseases Introduction HIV M184I;M184V 142;142 149;149 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. It must be noted, that analysis of the ECHO and THRIVE clinical data indicated that the presence of V90I, V106I, V179I and V189I was not associated with virological failure; therefore, these mutations are not likely to be associated with RPV resistance in vivo . 2014 Journal of the International AIDS Society Introduction HIV V106I;V179I;V189I;V90I 106;113;123;100 111;118;128;104 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Major RPV resistance-associated mutations have been included in the International AIDS Society-USA (IAS-USA) guidelines with K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L, as well as the recently added Y188L, defined as associated with key resistance. 2014 Journal of the International AIDS Society Introduction HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 134;134;134;134;134;174;167;125;125;184;184;149;156;156;156;223 147;147;147;147;147;179;172;132;132;191;191;154;165;165;165;228 AIDS 82 86 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Moreover, in numerous in vivo and in vitro studies, other candidate drug resistance mutations have been identified, including V90I, L100I, K101H/T, V106L, E138S,V179F/D/G/I/T, V189, G190A/E/S, F227L and M230V. 2014 Journal of the International AIDS Society Introduction HIV E138S;V179D;V179F;V179G;V179I;V179T;F227L;G190A;G190E;G190S;K101H;K101T;L100I;M230V;V106L;V90I 155;161;161;161;161;161;193;182;182;182;139;139;132;203;148;126 160;174;174;174;174;174;198;191;191;191;146;146;137;208;153;130 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. One of the characteristic features of this substance is the distinct drug resistance profile with full activity retained in the presence of the commonly transmitted and efavirenz-selected K103N mutation. 2014 Journal of the International AIDS Society Introduction HIV K103N 188 193 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Although RPV has been reported to have higher in vitro genetic barrier to resistance, at least 17 single substitutions in HIV-1 RT (L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, and M230I/L) have been associated with a decreased virologic response to this NNRTI. 2014 Antiviral research Introduction HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;L100I;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 148;148;148;148;148;195;188;139;139;132;206;206;163;170;170;170;181 161;161;161;161;161;200;193;146;146;137;213;213;168;179;179;179;186 NNRTI;RT 280;128 285;130 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Collectively, our data shows that the E138A mutation in HIV-1 RT is ~3-fold more common in naive- and RTI-experienced isolates from individuals infected with subtype C, compared to those infected with other subtypes, in 4 independent datasets. 2014 Antiviral research Introduction HIV E138A 38 43 RT;RT 102;62 105;64 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Consistent with these findings, an analysis of 2578 sequences (majority subtype C) from both naive and RTI-experienced (but with no prior exposure to RPV or etravirine (ETR)) HIV-1-infected individuals in the Lancet Laboratories (South African) database revealed that 206 (8%), 43 (1.7%), 29 (1.1%) and 23 (0.9%) harbored the E138A, G, K or Q mutations, respectively (data not shown). 2014 Antiviral research Introduction HIV E138A 326 331 RT 103 106 HIV infections 175 189 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. E138A was also found to reduce susceptibility to ETR, but did not significantly reduce susceptibility to NVP or EFV in either subtype B or C. 2014 Antiviral research Introduction HIV E138A 0 5 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. E138A was also more common in subtype C than B sequences from RTI-experienced HIV-1-infected individuals in the Stanford University and BC Centre databases (p < 0.01 in both databases) (Table 1), but its frequency was not higher in either subtype B or C sequences from individuals who had NRTI, but not NNRTI, containing regimens or those who received both NRTI- and NNRTI containing regimens (Table 1). 2014 Antiviral research Introduction HIV E138A 0 5 NNRTI;NNRTI;NRTI;NRTI;RT 303;367;289;357;62 308;372;293;361;65 HIV infections 78 92 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. For example, the V106M RT substitution, which confers resistance to the NNRTIs efavirenz (EFV) and nevirapine (NVP), has been reported more frequently in subtype C viruses than in subtype B. 2014 Antiviral research Introduction HIV V106M 17 22 NNRTI;RT 72;23 78;25 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. However, in the WHO TDR surveys, E138A was also more frequently observed in subtype A (6.0 %; p = 0.02), but not in subtypes D (0 %), G (5.9 %; p = 0.22), CRF01 (0.4 %), CRF02 (2.0 %), CRF06 (0 %), CRF07 (0 %), CRF08 (2.6 %) and CRF11 (0 %) (Supplementary Table 1). 2014 Antiviral research Introduction HIV E138A 33 38 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In contrast to E138A, the frequencies of other substitutions at codon 138 (i.e., E138G/K/Q) were similar in both subtypes B and C. 2014 Antiviral research Introduction HIV E138A;E138G;E138K;E138Q 15;81;81;81 20;90;90;90 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In subtype C RT, the E138G/K/Q/R mutations reduced susceptibility to RPV and ETR (range: 2.7-6.8-fold). 2014 Antiviral research Introduction HIV E138G;E138K;E138Q;E138R 21;21;21;21 32;32;32;32 RT 13 15 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In the BC database, E138A was present in 76/3320 (2.3%) subtype B sequences compared to 6/101 (5.9%) subtype C sequences (p=0.03). 2014 Antiviral research Introduction HIV E138A 20 25 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In the context of subtype C RT, the E138A substitution reduces virus susceptibility to RPV. 2014 Antiviral research Introduction HIV E138A 36 41 RT 28 30 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In the Stanford University database, E138A was present in 350/17481 (2.0%) subtype B sequences and in 415/6795 (6.1%) subtype C sequences from RTI-naive HIV-1-infected individuals (p<0.0001). 2014 Antiviral research Introduction HIV E138A 37 42 RT 143 146 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In the Stanford University HIV Database, E138K and E138Q were also more common in subtype C than B isolates from RTI-experienced individuals, although their overall frequencies (1.0% and 1.1%, respectively) were lower than E138A (6.1%). 2014 Antiviral research Introduction HIV E138A;E138K;E138Q 223;41;51 228;46;56 RT 113 116 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. In the WHO TDR surveys, E138A was not observed in subtype B sequences, but was present in 97/1296 (7.5%) subtype C sequences (p<0.01). 2014 Antiviral research Introduction HIV E138A 24 29 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Interestingly, the E138K/Q/R mutations in HIV-1 subtype C had noticeable effects on NVP and EFV susceptibility (2.3 to 7.1-fold). 2014 Antiviral research Introduction HIV E138K;E138Q;E138R 19;19;19 28;28;28 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Of note, in the Stanford University database E138A was not more common in treatment-naive sequences of other subtypes, including subtypes A (3.2%), D (2.3%), F (3.6%), G (1.7%), CRF01 (0.4%) or CRF02 (2.3%). 2014 Antiviral research Introduction HIV E138A 45 50 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Taken together, these data indicate that E138A is polymorphic and does not appear to be strongly selected by prior RTI exposure. 2014 Antiviral research Introduction HIV E138A 41 46 RT 115 118 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. The E138A mutation reduced susceptibility to RPV by 5.6-fold in HIV-1 subtype B and by 2.9-fold in HIV-1 subtype C, respectively. 2014 Antiviral research Introduction HIV E138A 4 9 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. The E138G/K/Q/R mutations in HIV-1 subtype B reduced susceptibility to RPV and ETR but, with the exception of E138Q which decreased susceptibility to NVP 3.0-fold, had no impact on susceptibility to either NVP or EFV. 2014 Antiviral research Introduction HIV E138G;E138K;E138Q;E138Q;E138R 4;4;4;110;4 15;15;15;115;15 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. The higher frequency of E138A in subtype C may also compromise the efficacy of RPV-LA as a PrEP agent in sub-Saharan Africa, although additional studies are warranted to assess this possibility. 2014 Antiviral research Introduction HIV E138A 24 29 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. Therefore, we introduced the E138A, E138G, E138K, E138Q and E138R mutations into subtype C RT, as described previously, and assessed virus susceptibility to RPV, ETR, EFV and NVP in P4/R5 cells (Table 2). 2014 Antiviral research Introduction HIV E138A;E138G;E138K;E138Q;E138R 29;36;43;50;60 34;41;48;55;65 RT 91 93 24746459 E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings. We found that the E138A substitution in HIV-1 RT occurs more frequently in subtype C than B sequences from both treatment-naive and -experienced individuals (Table 1). 2014 Antiviral research Introduction HIV E138A 18 23 RT 46 48 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. By combining REST with lambda-hopping (replica exchange between neighboring lambda windows), the consistency of binding free energies was found to improve markedly for two problematic cases, namely, the binding of p-xylene and benzene to lysozyme L99A, which requires the correct conformational ensemble of side chain dihedral angles in the protein to achieve FEP results that are independent of the starting conformation, and the sampling of ring flips in ligands bound to thrombin. 2014 Journal of chemical theory and computation Introduction HIV L99A 247 251 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. In particular, 1b (R = H, X = Cl) has an EC50 of 6 nM toward wild-type HIV-1 and 420 nM toward the Y181C variant. 2014 Journal of chemical theory and computation Introduction HIV Y181C 99 104 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. In what follows, we describe the implementation of REST within MCPRO, benchmark the performance of the combined REST/flip method in the isopropyl to ethyl FEP transformation in the wild-type protein, and, finally, present activity predictions of seven analogs of 1b toward the wild-type and Y181C strains. 2014 Journal of chemical theory and computation Introduction HIV Y181C 291 296 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. These inhibitors are an important component of treatment against HIV infection, but patients who begin NNRTI therapy often develop the Y181C mutation, thus rendering common drugs inactive. 2014 Journal of chemical theory and computation Introduction HIV Y181C 135 140 NNRTI 103 108 HIV infections 65 78 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. We apply the combined REST/flip methodology to the optimization of non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs), with a particular view to enhancing potency against the Tyr181Cys (Y181C) mutant form. 2014 Journal of chemical theory and computation Introduction HIV Y181C;Y181C 190;201 199;206 RT;NNRTI 102;125 123;131 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Two exceptions to this pattern were G84D and D104A, which had a stronger effect on the Vif-CUL5 interaction than on the Vif-CBF-beta interaction. 2014 PloS one Introduction HIV D104A;G84D 45;36 50;40 Vif;Vif 87;120 90;123 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. These studies noted very similar reverse transcriptase (RT) resistance patterns as compared to adults, with M184V and K103N being the most prevalent mutations. 2014 PloS one Introduction HIV K103N;M184V 118;108 123;113 RT;RT 33;56 54;58 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. Furthermore, MINIs inhibited the HIV-1 variant with the A128T IN substitution, which confers resistance to the majority of ALLINIs. 2014 PLoS pathogens Introduction HIV A128T 56 61 IN 62 64 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. In particular, A128T substitution is most common and has been shown to confer marked resistance to the majority of ALLINIs. 2014 PLoS pathogens Introduction HIV A128T 15 20 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. At last, we analyze the potential interaction between sits 181 and 221 in the background of K101Q. 2014 BMC infectious diseases Introduction HIV K101Q 92 97 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. H221Y, which had been believed to emerge in NRTI-treatment patients and considered to be polymorphism , proved to be a novel mutation correlated with NNRTI-resistance in 2003. 2014 BMC infectious diseases Introduction HIV H221Y 0 5 NNRTI;NRTI 150;44 155;48 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Here, we are focused on defining the role of K101Q, Y181C, H221Y emerging in different patterns. 2014 BMC infectious diseases Introduction HIV H221Y;K101Q;Y181C 59;45;52 64;50;57 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, it had been certified that the frequency of H221Y significantly increased in NNRTI-treatment failing patients compared with drug-naive and NRTI-treated NNRTI-naive patients . 2014 BMC infectious diseases Introduction HIV H221Y 53 58 NNRTI;NNRTI;NRTI 86;161;148 91;166;152 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, the common NNRTI mutations were K103N and Y181C whose roles in NNRTI-resistance have been clarified . 2014 BMC infectious diseases Introduction HIV K103N;Y181C 41;51 46;56 NNRTI;NNRTI 20;72 25;77 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. It was demonstrated that K101Q with H221Y as an unreported HIV-1 RT mutation pattern was associated with phenotypic resistance to the NNRTI class . 2014 BMC infectious diseases Introduction HIV H221Y;K101Q 36;25 41;30 NNRTI;RT 134;65 139;67 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Moreover, H221Y was strongly associated with the use of NVP and showed positive interactions with Y181C . 2014 BMC infectious diseases Introduction HIV H221Y;Y181C 10;98 15;103 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. With an unusual GPEK sequence instead of the typical GPGR crown motif in V3 of the envelope glycoprotein, ZP6248 used GPR15 very efficiently, while the V3 crown mutant E314G could enable ZP6248 to infect CCR5+ cells, suggesting that V3 plays an important role in GPR15 tropism. 2014 PloS one Introduction HIV E314G 168 173 Env 83 91 24909578 Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia. Furthermore, presence of the I164L substitution in dhfr or the A581G substitution in dhps is associated with reduced efficacy of SP in vitro and in vivo. 2014 Malaria journal Introduction HIV A581G;I164L 63;29 68;34 24909578 Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia. One study of the general community in Macha, Zambia in 2006 found the quintuple marker in 6.5% of samples, and no I164L mutations, compared to the absence of these markers in 2000 in the same community. 2014 Malaria journal Introduction HIV I164L 114 119 24909578 Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia. The quintuple mutant haplotype, consisting of the N51I, C59R, S108N substitutions in dhfr and the A437G and K540E substitutions in dhps is a marker for SP treatment failure in non-pregnant patients. 2014 Malaria journal Introduction HIV A437G;C59R;K540E;N51I;S108N 98;56;108;50;62 103;60;113;54;67 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. HIV-1 resistance to AZT is associated with selection of the thymidine analog mutations (TAMs) M41L, D67N, K70R, L210W, T215F/Y and K219Q/E in RT. 2014 The Biochemical journal Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 100;131;131;106;112;92;119;119 104;138;138;110;117;98;126;126 RT 142 144 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. The effects of the single secondary mutations, L63P, on the conformational sampling of subtype B (LAI) sequence was also investigated because it is a common natural polymorphism contained within the PRE sequence. 2014 FEBS letters Introduction HIV L63P 47 51 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. In HIV-1 CRF01_AE infection, the RT mutations T69N and V75M were seen more frequently than in HIV-1 subtype B. 2014 PloS one Introduction HIV T69N;V75M 46;55 50;59 RT 33 35 HIV infections 3 27 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K103N and Y181C are the major nucleoside reverse transcriptase inhibitors (NNRTI) mutations selected under nevirapine (NVP) prophylaxis which is still used in low resource settings as a core component of interventions to prevent mother-to-child HIV-1 transmission (pMTCT). 2014 Journal of virological methods Introduction HIV Y181C;K103N 10;0 15;5 NRTI;NNRTI 30;75 62;80 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The purpose of this study was to compare the concordance and quantity of the Y181C and K103N mutations detected by AS-PCR and UDPS methodologies in the cohort of infants undergoing switch to nevirapine-based ART mentioned above and to assess the utility of the more rapid, and cheaper AS-PCR assays in settings where this has been optimized. 2014 Journal of virological methods Introduction HIV K103N;Y181C 87;77 92;82 25101529 2014 Update of the drug resistance mutations in HIV-1. The following mutations have been added to existing classes or drugs: K65E/N has been added to the bars for the nucleoside and nucleotide analogue reverse transcriptase inhibitors (nRTIs) abacavir, didanosine, emtricitabine, lamivudine, stavudine, and tenofovir; L100I has been added to the bar for the nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) rilpivirine; and F121Y has been added to the bars for the integrase strand transfer inhibitors (InSTIs) dolutegravir, elvitegravir, and raltegravir. 2014 Topics in antiviral medicine Introduction HIV F121Y;K65E;K65N;L100I 383;70;70;263 388;76;76;268 RT;RT;IN;INSTI;NNRTI;NRTI 147;326;424;462;359;181 168;347;433;468;364;186 25108107 A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF. 1), was co-crystallized with four clinically relevant variants of MDR769 HIV-1 protease, I10V, A82F, A82S and A82T. 2014 Journal of molecular graphics & modelling Introduction HIV A82F;A82S;A82T;I10V 95;101;110;89 99;105;114;93 PR 79 87 25108107 A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF. The multidrug-resistant (MDR)-769 HIV-1 protease consists of amino acid substitutions: L10I, M36V, M46L, I54V, I62V, L63P, A71V, V82A, I84V and L90M. 2014 Journal of molecular graphics & modelling Introduction HIV A71V;I54V;I62V;I84V;L10I;L63P;L90M;M36V;M46L;V82A 123;105;111;135;87;117;144;93;99;129 127;109;115;139;91;121;148;97;103;133 PR 40 48 25136270 Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease. This variant Flap+ (L10I/G48V/I54V/V82A) was derived as a combination of mutations that simultaneously occur in patient sequences. 2014 Journal of chemical theory and computation Introduction HIV G48V;I54V;L10I;V82A 25;30;20;35 29;34;24;39 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. M184V causes high-level resistance to lamivudine and emtricitabine and low-level resistance to didanosine and abacavir. 2014 Journal of the International AIDS Society Introduction HIV M184V 0 5 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. M184V is another important mutation which is also the most commonly occurring NRTI RAM. 2014 Journal of the International AIDS Society Introduction HIV M184V 0 5 NRTI 78 82 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Q151M is usually accompanied by the mutations A62V, V75I, F77L and F116Y. 2014 Journal of the International AIDS Society Introduction HIV A62V;F116Y;F77L;V75I;Q151M 46;67;58;52;0 50;72;62;56;5 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. The presence of TAMs, 69Ins, Q151M and M184V at first-line ART failure can compromise treatment options for second-line therapy. 2014 Journal of the International AIDS Society Introduction HIV M184V;Q151M 39;29 44;34 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. The Q151M complex affects all approved NRTIs except for tenofovir. 2014 Journal of the International AIDS Society Introduction HIV Q151M 4 9 NRTI 39 44 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. There are two TAM pathways: type I (M41L, L210W and T215Y) and type II (D67N, K70R, T215F and K219Q/E); the former conferring higher levels of resistance and cross-resistance. 2014 Journal of the International AIDS Society Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 72;94;94;78;42;36;84;52 76;101;101;82;47;40;89;57 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Three drug resistance patterns including thymidine analogue-associated mutations (TAMs), 69 Insertion (69Ins) and Q151M complex are associated with multi-NRTI drug resistance. 2014 Journal of the International AIDS Society Introduction HIV Q151M 114 119 NRTI 154 158 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. We investigated the patterns and factors associated with multi-NRTI RAMs, defined as the presence of either Q151M; 69Ins; >=2 TAMs; or M184V+>=1 TAM, at first-line failure in an Asian HIV cohort where stavudine use was predominant, and evaluated the impact of these RAMS on virological responses at 12 months after switch to second-line ART. 2014 Journal of the International AIDS Society Introduction HIV M184V;Q151M 135;108 140;113 NRTI 63 67 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. When present with TAMS, M184V can increase resistance to abacavir. 2014 Journal of the International AIDS Society Introduction HIV M184V 24 29 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. 3TC treatment of HIV-1 infected patients selects for drug-resistant variants with sequential mutation at position 184 from Met to Ile, followed by Ile to Val. 2014 PloS one Introduction HIV M184I 114 133 HIV infections 17 31 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The M184V substitution is associated with high-level resistance to 3TC and K65R mutation confers intermediate to high-level resistance to the 3TC. 2014 PloS one Introduction HIV K65R;M184V 75;4 79;9 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Though the hydrochloride salt of FNC did show good suppression to NRTI-resistant viral strains, the antiviral activity decreased upon M184V mutation of HIV-1. 2014 PloS one Introduction HIV M184V 134 139 NRTI 66 70 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. We previously reported that the Tat protein in 88% of HIV-1C isolates worldwide have a C31S polymorphism, which disrupts a dicysteine motif that is highly conserved (99%) in all the other clades. 2014 PloS one Introduction HIV C31S 87 91 Tat 32 35 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. We, along with several other groups, have shown that the C31S polymorphism in HIV-1 Tat-C is also responsible for a compromised ability of Tat to induce proinflammatory chemokines/cytokines and to cause direct neurotoxicity. 2014 PloS one Introduction HIV C31S 57 61 Tat;Tat 84;139 87;142 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. has an EC50 of 6 nM towards the wild-type protein, but 420 nM towards the variant strain bearing the Y181C mutation. 2015 Biochimica et biophysica acta Introduction HIV Y181C 101 106 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. The Y181C variant was generated manually from the wild-type structure. 2015 Biochimica et biophysica acta Introduction HIV Y181C 4 9 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. This class of molecules is an important component of anti-HIV treatment; however, patients who begin NNRTI treatment often develop the Tyr181Cys (Y181C) mutation, which renders many agents inactive. 2015 Biochimica et biophysica acta Introduction HIV Y181C;Y181C 135;146 144;151 NNRTI 101 106 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We further demonstrate that K103N, a clinically observed mutant that confers viral resistance to EFV, does not affect NNRTI binding but instead directly targets and prevents this allosteric mechanism. 2014 Nucleic acids research Introduction HIV K103N 28 33 NNRTI 118 123 25239368 Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C. Also, the probes for detection of V106M and G190A were not optimized for Zimbabwean HIV variants as indeterminate OLA results appeared to be caused by a variety of polymorphisms that could not be readily incorporated into new probes. 2014 Journal of virological methods Introduction HIV G190A;V106M 44;34 49;39 25239368 Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C. An economical oligonucleotide ligation assay (OLA) was developed to detect mutations generally associated with HIV-DR to NVP (K103N, Y181C, V106M and G190A) and other antiretrovirals (ARVs). 2014 Journal of virological methods Introduction HIV G190A;K103N;V106M;Y181C 150;126;140;133 155;131;145;138 25239368 Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C. Concordant OLA results between the two laboratories were as follow: K103N (100%), V106M (39/40; 97.5%); Y181C, (38/40; 95%), and G190A (100%). 2014 Journal of virological methods Introduction HIV G190A;K103N;V106M;Y181C 129;68;82;104 134;73;87;109 25239368 Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C. DNA was extracted from the DBS using Chelex-100 and HIV pol was amplified by nested PCR and tested with OLA probes for NVP-associated mutations K103N, Y181C, V106M and G190A designed using HIV subtype C sequences published in the Los Alamos National Laboratory (LANL) HIV database (http://www.hiv.lanl.gov/content/index) and are referred to in this paper as "generic probes". 2014 Journal of virological methods Introduction HIV G190A;K103N;V106M;Y181C 168;144;158;151 173;149;163;156 Pol 56 59 25239368 Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C. The objective of this study was to transfer the OLA to a Zimbabwean laboratory, optimize OLA reagents to detect the four NVP-resistance mutations (K103N, Y181C, V106M and G190A) in Zimbabwean infants, and validate the performance of the Zimbabwe-specific OLA reagents in the Zimbabwean laboratory for potential use in the detection of NVP resistant mutations in infants infected through MTCT. 2014 Journal of virological methods Introduction HIV G190A;K103N;V106M;Y181C 171;147;161;154 176;152;166;159 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Altogether, these observations suggest that R263K may represent an evolutionary dead-end that could explain the scarcity of virological failures and resistance mutations in individuals treated with DTG. 2014 Viruses Introduction HIV R263K 44 49 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Further studies have shown that secondary mutations in integrase at positions H51Y and E138K that are associated with R263K failed to restore viral fitness. 2014 Viruses Introduction HIV E138K;H51Y;R263K 87;78;118 92;82;123 IN 55 64 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Moreover, the use of DTG to treat patients who had previously failed multiple drugs but who were naive to INSTIs resulted in treatment failure in relatively few individuals, only two of whom developed the R263K mutation. 2014 Viruses Introduction HIV R263K 205 210 INSTI 106 112 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Because it is also well established that phosphorylation can generally trigger ubiquitination, these cumulative results prompted us to investigate the interaction of S40F mutant Gag with the ubiquitin proteasome system (UPS). 2014 Viruses Introduction HIV S40F 166 170 Gag 178 181 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Here we show that the S40F mutation specifically leads to the formation of a hydrophobic patch on the C-terminal alpha-helix of p6 which consequently enhances the membrane interaction of Gag. 2014 Viruses Introduction HIV S40F 22 26 Gag;Gag 187;128 190;130 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. However, and unlike l-domain mutants, the exchange of Ser-40 to Phe (S40F) causes no defect in virus release, but specifically induces Gag-containing membrane protrusions resembling filopodia. 2014 Viruses Introduction HIV S40F;S40F 69;54 73;67 Gag 135 138 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In addition, the S40F mutation interferes with the Nedd4 ubiquitin ligase mediated virus release. 2014 Viruses Introduction HIV S40F 17 21 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Moreover, the ALIX-interacting protein syntenin, which is known to bind both K48- and K63-linked polyubiquitin, has been speculated to play a role in the process of S40F-mediated filopodia formation. 2014 Viruses Introduction HIV S40F 165 169 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. This augmented membrane association of the S40F mutant is accompanied, similar to the mutation of the PTAP l-domain, by increased K48-linked polyubiquitination of Gag and, thus, enhances its entry into the UPS. 2014 Viruses Introduction HIV S40F 43 47 Gag 163 166 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Certain mutations, including those at positions G367R and D368R in the CD4 binding site (CD4bs) of gp120, may cause the virus to become non-infectious. 2014 Virology journal Introduction HIV D368R;G367R 58;48 63;53 gp120 99 104 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Here, we report that some env mutants may perform differently in cell-free versus cell-to-cell transmission and that a G367R mutant can spontaneously revert in some T cell lines. 2014 Virology journal Introduction HIV G367R 119 124 Env 26 29 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. In this manuscript, we show that the defectiveness of the G367R mutation is more severe in the context of free virus than cell-associated virus, but only in certain types of cells. 2014 Virology journal Introduction HIV G367R 58 63 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Interestingly, interleukin 2 (IL2) can block G367R reversion in MT2 cells but not in SupT1 cells, while PMA is able to inhibit reversion in both cell types, suggesting that complex mechanisms are involved in the reversion process. 2014 Virology journal Introduction HIV G367R 45 50 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. We also report that G367R reversion was slowed or inhibited by HIV entry inhibitors, such as the gp120 binding agent DS003 and the CXCR4 antagonist AMD3100, as well as by inhibitors of endocytosis at sub-toxic concentrations. 2014 Virology journal Introduction HIV G367R 20 25 gp120 97 102 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. We have previously documented that a substitution in Env at position G367R can result in viral non-infectiousness and that this deficit can be rescued by recombination. 2014 Virology journal Introduction HIV G367R 69 74 Env 53 56 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. Although K65R is selected by nucleotide reverse transcriptase inhibitor tenofovir (TDF) usually, it can be selected by d4T. 2014 PloS one Introduction HIV K65R 9 13 RT 40 61 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. As an initial approach, we focused on designing an assay for six major DR mutations: M41L, K65R, K70R, K103N, M184V and T215Y/F. 2014 PloS one Introduction HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y 103;91;97;110;85;120;120 108;95;101;115;89;127;127 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K103N is highly associated with EFV and NVP resistance. 2014 PloS one Introduction HIV K103N 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K65R is associated multi-nucleoside and nucleotide DR. 2014 PloS one Introduction HIV K65R 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. M184V is highly associated with 3TC and emtricitabine (FTC) resistance, and reduce the susceptibility to 3TC by 200-fold. 2014 PloS one Introduction HIV M184V 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. M41L, K70R, T215F/Y are examples of thymidine analogue mutations (TAMs) and associated with AZT and d4T (HIV Drug resistance database, Stanford University, http://hivdb.stanford.edu/index.html). 2014 PloS one Introduction HIV K70R;T215F;T215Y;M41L 6;12;12;0 10;19;19;4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. The K103N mutation reduces susceptibility to NVP by 50-flod, and EFV by 20-fold. 2014 PloS one Introduction HIV K103N 4 9 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. For this purpose, the most prominent NNRTI mutations, K103N and Y181C, were investigated by a highly sensitive AS-PCR and the results were compared with direct population sequencing. 2014 PloS one Introduction HIV K103N;Y181C 54;64 59;69 NNRTI 37 42 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. A nucleotide is added to the end of the misaligned primer, the primer and template strands realign, and the resulting point mutation leads to the K65R substitution (see Figure 2). 2014 Viruses Introduction HIV K65R 146 150 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Accumulation of the K65R mutation has been shown to decrease the overall catalytic efficiency of HIV-1 RT up to 3-fold, almost entirely due to a reduced rate of incorporation (kpol). 2014 Viruses Introduction HIV K65R 20 24 RT 103 105 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Additionally, and a further reason for the rarity of TAMs and K65R together in a clinical setting, the antagonistic effect of K65R and TAM was shown to be bidirectional; the presence of the TAM mutations increases sensitivity to tenofovir in viruses containing the K65R substitution. 2014 Viruses Introduction HIV K65R;K65R;K65R 62;126;265 66;130;269 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Although K65R confers cross-resistance only to NRTIs other than AZT, it actually increases the susceptibility of virus containing the TAM mutations i.e., K65R is antagonistic to resistance via TAMs. 2014 Viruses Introduction HIV K65R;K65R 9;154 13;158 NRTI 47 52 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Although the steric restraint imposed by the stacked guanidinium planes suggests a mechanism for resistance to nucleoside analogs, it does not explain the antagonistic relationship between K65R and the TAM mutations. 2014 Viruses Introduction HIV K65R 189 193 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Antagonism of K65R with other NRTI-Resistance Mutations. 2014 Viruses Introduction HIV K65R 14 18 NRTI 30 34 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Biochemical and structural studies of this variant of RT have yielded important insights into how M184V alteration confers discrimination between the normal dNTP substrate and the NRTI analog, 3TC triphosphate (3TCTP) through the exclusion mechanism. 2014 Viruses Introduction HIV M184V 98 103 NRTI;RT 180;54 184;56 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Clinical Prevalence of K65R. 2014 Viruses Introduction HIV K65R 23 27 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Data from this study shows that while K65R was present in 82% of genomes without TAMs, and at low frequency in the presence of <3 TAMs; no sequences were identified with K65R, T215F/Y and >= 2 TAMs in the absence of the Q151M multi-drug resistant complex. 2014 Viruses Introduction HIV K65R;K65R;Q151M;T215F;T215Y 38;170;220;176;176 42;174;225;183;183 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Even with tenofovir treatment, the occurrence of K65R in the patient population is typically below 5%; however, as described below, this frequency is increased depending on HIV-1 subtype, geographical location and treatment regimen. 2014 Viruses Introduction HIV K65R 49 53 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Excluding subjects that likely had the mutation as a result of a transmitted resistant variant, 35.7% (10 of 28) of patients with subtype C HIV-1 infection had a low level of K65R variants, compared to only 2.2% (2 of 92) in subtype B. 2014 Viruses Introduction HIV K65R 175 179 HIV infections 140 155 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Further, the K65R substitution has an effect on polymerase fidelity; incorporation of an incorrect nucleotide into a nascent DNA chain requires both misinsertion and the extension of the resulting mismatched primer. 2014 Viruses Introduction HIV K65R 13 17 Pol 48 58 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Furthermore, it was shown that it was the nucleotide sequence surrounding the K65R codon, in particular a polyadenine stretch terminating at the position which is mutated in the lysine to arginine substitution, that is responsible for the difference in selection. 2014 Viruses Introduction HIV K65R 78 82 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Given the importance of the K65 residue in HIV-1 RT function and the observed reduced fitness of K65R mutants, it is no surprise that compensatory mutations would evolve to counteract this defect. 2014 Viruses Introduction HIV K65R 97 101 RT 49 51 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. have shown that K65R mutant virus can be inhibited 70-times more efficiently by EFdA than by TDF. 2014 Viruses Introduction HIV K65R 16 20 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. However in another study of HIV-1 subtype C pediatric patients from Botswana, all of whom had failed first-line therapy, K65R was observed at a low frequency (<5%). 2014 Viruses Introduction HIV K65R 121 125 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. However, analysis of the structure demonstrates that the K65R-R72 guanidinium stacking, the basis of the mechanism for K65R dependent resistance to NRTI, would interfere with the positioning of ATP by Arg70. 2014 Viruses Introduction HIV K65R;K65R 57;119 61;123 NRTI 148 152 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. However, as was the case for K65R prevalence following treatment, the situation in treatment-naive patients is also complicated; in a second study that aggregated mutation rates from a series of studies of treatment-naive patients, K65R was found to be very rare (0.1%) and, interestingly, differences in prevalence between subtypes was not significant. 2014 Viruses Introduction HIV K65R;K65R 29;232 33;236 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In a finding that could indicate that subtype differences can inform treatment choices, it was discovered that the K65R mutation is selected rapidly in subtype C viruses in cell culture as a result of tenofovir treatment. 2014 Viruses Introduction HIV K65R 115 119 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In a situation that mirrors that found in the subtype B virus, the presence of TAMs also reduces selection of K65R in the subtype C virus (although not to the extent seen in subtype B). 2014 Viruses Introduction HIV K65R 110 114 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In addition to the increased frequency of the K65R substitution as a result of drug pressure, there is evidence that the mutation may be more prevalent in drug-naive subtype C infected patients than in patients infected with subtype B. 2014 Viruses Introduction HIV K65R 46 50 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In addition, the decrease in tenofovir susceptibility of the K65R mutant has been associated with a reduction in RT processivity in vitro. 2014 Viruses Introduction HIV K65R 61 65 RT 113 115 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In Europe and the USA, the K65R mutation is rarely observed clinically, although its frequency has increased over the last decade in parallel with the increased usage of tenofovir, as K65R is clinically associated with tenofovir resistance. 2014 Viruses Introduction HIV K65R;K65R 27;184 31;188 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In one study, virus from 50% of patients (4/8) who developed the K65R mutation following tenofovir treatment also contained at least one of the A62V or S68G mutations; however, in all patients with the K65R virus, viremia did not return to the pre-treatment baseline, potentially reflecting the effect of K65R on viral fitness. 2014 Viruses Introduction HIV A62V;K65R;K65R;K65R;S68G 144;65;202;305;152 148;69;206;309;156 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In the K65R mutant RT, both the R72 and R65 residues are restrained due to the guanidinium stacking of the arginines, and an additional stacking interaction between the R72 guanidinium and the incoming base (see Figure 1). 2014 Viruses Introduction HIV K65R 7 11 RT 19 21 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. In vitro experiments with purified recombinant RT carrying the K65R mutation recapitulated cross-resistance to the dideoxynucleoside inhibitors, and showed only a modest effect on AZT resistance. 2014 Viruses Introduction HIV K65R 63 67 RT 47 49 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Indeed, as described below, the K65R mutation is antagonistic to resistance occurring through post-incorporation excision. 2014 Viruses Introduction HIV K65R 32 36 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Interestingly, the K65R mutation appeared instead to cause hypersusceptibility by decreasing the rate of excision of EFdA from the primer termini. 2014 Viruses Introduction HIV K65R 19 23 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Investigations into the mechanistic basis of this hypersusceptibility showed the K65R mutation did not significantly enhance the susceptibility to EFdA either by affecting its incorporation or by affecting enzyme translocation on EFdA-MP-terminated template/primers. 2014 Viruses Introduction HIV K65R 81 85 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. It is now known that K65R is associated with resistance to most of the NRTI drugs, including Abacavir (ABC), Emtricitabine (FTC), Lamivudine (3TC), Stavudine (d4T) and, in particular, Tenofovir. 2014 Viruses Introduction HIV K65R 21 25 NRTI 71 75 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. K65R Confers Hypersusceptibility to other NRTIs. 2014 Viruses Introduction HIV K65R 0 4 NRTI 42 47 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Other substitutions have been described (K65E and K65N), but are much less common than K65R. 2014 Viruses Introduction HIV K65E;K65N;K65R 41;50;87 46;54;91 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Q151 is mutated to methionine (Q151M) in response to treatment with dideoxynucleoside analogs and usually occurs in combination with A62V, V75I, F77L, and F116Y mutations. 2014 Viruses Introduction HIV A62V;F116Y;F77L;Q151M;V75I 133;155;145;31;139 137;160;149;36;143 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Several mutations (the thymidine analog mutations, TAM) are required for high-level AZT resistance by excision, and include M41L, D67N, K70R, T215F or Y and K219E or Q. 2014 Viruses Introduction HIV D67N;K219E;K70R;M41L;T215F 130;157;136;124;142 134;162;140;128;147 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Some studies show extensive selection of K65R in subtype C virus following treatment with didanosine (up to 30% K65R) following failure of first-line treatment with a combination NRTI/NNRTI combination therapy. 2014 Viruses Introduction HIV K65R;K65R 41;112 45;116 NNRTI;NRTI 184;179 189;183 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Studies using purified and virion associated RTs on stretches of homopolymeric and heteropolymeric templates show decreased processivity for K65R RT under limiting substrate concentrations. 2014 Viruses Introduction HIV K65R 141 145 RT;RT 45;146 48;148 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The association of Q151M and other Q151M complex mutations with K65R, T215F/Y and other TAMs suggests that the Q151M complex is necessary to confer NRTI resistance in the presence of K65R and TAM antagonism. 2014 Viruses Introduction HIV K65R;K65R;Q151M;Q151M;Q151M;T215F;T215Y 64;183;19;35;111;70;70 68;187;24;40;116;77;77 NRTI 148 152 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The decreased rate of excision is attributed to the conformational constraints of K65R and Arg72, as described in the following section. 2014 Viruses Introduction HIV K65R 82 86 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The K65R has been shown in vitro to decrease the rate of pyrophosphorolysis and is predicted to reduce ATP-mediated excision of AZTMP. 2014 Viruses Introduction HIV K65R 4 8 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The K65R mutant enzyme primarily confers resistance through the exclusion (discrimination) mechanism. 2014 Viruses Introduction HIV K65R 4 8 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The K65R mutation, which perturbs the geometry of the nucleotide bound in the active site, while retaining the stabilization of the cognate nucleotide required for polymerization, was identified in samples from patients who had undergone treatment with the 2'-3'dideoxynucleoside inhibitor ddC. 2014 Viruses Introduction HIV K65R 4 8 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The K65R substitution, although conservative in nature, has the effect of reducing the steric flexibility of the RT active site by the formation of a molecular platform through the stacking of the guanidinium planes of the R65 and R72 residues. 2014 Viruses Introduction HIV K65R 4 8 RT 113 115 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The mechanism of nucleoside analog resistance mediated through K65R mutation, however, is exclusively through selection against incorporation, rather than an increase in excision. 2014 Viruses Introduction HIV K65R 63 67 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The Q151M complex consists of five mutations (Q151M/A62V/V75I/F77L/F116Y), of which Q151M is one of the primary mutations to emerge. 2014 Viruses Introduction HIV A62V;F116Y;F77L;Q151M;V75I;Q151M;Q151M 52;67;62;46;57;4;84 56;72;66;51;61;9;89 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The Q151M complex of mutations confers resistance to multiple NRTIs by allowing the enzyme to discriminate against the NRTI analogs. 2014 Viruses Introduction HIV Q151M 4 9 NRTI;NRTI 62;119 67;123 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The simplest explanation for the finding was that differences between the amino acid sequence of the RTs from the two subtypes of HIV-1 may be responsible for the difference in mutation selection (such as presence of compensatory mutations in subtype C to overcome the inherent reduction in RT activity due to the K65R substitution). 2014 Viruses Introduction HIV K65R 314 318 RT;RT 101;291 104;293 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The structural basis for both the broad dideoxynucleotide resistance and the AZT resistance antagonism by K65R has been elucidated. 2014 Viruses Introduction HIV K65R 106 110 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The structural data suggests that the reduced polymerization rate of the K65R mutant could be due to this steric constraint. 2014 Viruses Introduction HIV K65R 73 77 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Therefore, it is not surprising that the K65R mutation occurs very rarely in conjunction with the TAM mutations given that there is no enhanced NRTI resistance as a result of K65R. 2014 Viruses Introduction HIV K65R;K65R 41;175 45;179 NRTI 144 148 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. These substitutions also play a role in NRTI resistance through a decrease in binding affinity (Km) for dNTP substrates, reduced phosphorolysis and catalytic efficiency, however, are presumably less frequent as they have an even more dramatic effect on viral fitness than K65R. 2014 Viruses Introduction HIV K65R 272 276 NRTI 40 44 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. This bidirectional antagonism has been demonstrated most recently in a study using single genome sequencing, whereby plasma samples with K65R mutation in the presence of TAMs were sequenced. 2014 Viruses Introduction HIV K65R 137 141 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. This class of mutations is exemplified by M184V, Q151M and K65R mutations. 2014 Viruses Introduction HIV K65R;M184V;Q151M 59;42;49 63;47;54 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. This lack of linkage between TAMs and K65R in vivo aligns with the functional antagonism of the mutants for each other as shown by biochemical studies. 2014 Viruses Introduction HIV K65R 38 42 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. This mechanism for the reduction in the rate of polymerization (kpol) is distinct from that of other NRTI resistance mutations, such as M184V that confer resistance by decreasing the binding affinity of the enzyme for the inhibitor. 2014 Viruses Introduction HIV M184V 136 141 NRTI 101 105 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Thus, the K65R mutation appears to reduce the efficiency with which AZT is removed from the primer terminus. 2014 Viruses Introduction HIV K65R 10 14 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Thus, the treatment regimen would be expected to influence the selection of K65R; initial treatment with AZT followed by tenofovir may result in a lower K65R frequency than the use of tenofovir as a front-line therapeutic. 2014 Viruses Introduction HIV K65R;K65R 76;153 80;157 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Two mutations in particular, A62V and S68G, have been found in association with K65R sequence databases and in vivo. 2014 Viruses Introduction HIV A62V;K65R;S68G 29;80;38 33;84;42 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Two of the canonical TAM mutations, K70R and T215Y, form a new ATP binding pocket, which is not present in the wild-type enzyme. 2014 Viruses Introduction HIV K70R;T215Y 36;45 40;50 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Ultimately, the stacking interaction between the R65, R72 and base of the incoming nucleotide is hypothesized to impose such a steric constraint that NRTIs cannot achieve the conformation necessary for incorporation in virus carrying the K65R mutation. 2014 Viruses Introduction HIV K65R 238 242 NRTI 150 155 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Ultra-deep sequencing was used to determine the proportion of a patient's viral load that contained the K65R substitution. 2014 Viruses Introduction HIV K65R 104 108 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. When the nucleotide sequence of lacZalpha mutants thus generated by K65R was analyzed, a uniform reduction in most types of RT errors, including substitutions and frameshifts, was noted. 2014 Viruses Introduction HIV K65R 68 72 RT 124 126 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. While K65R emerged after 12 weeks in subtype C, it was not detected in subtype B virus treated with the same regimen for up to 75 weeks. 2014 Viruses Introduction HIV K65R 6 10 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. While the double (A62V/K65R, S68G/K65R) or triple mutants (A62V/K65R/S68G) do not grossly affect NRTI (TFV, FTC, 3TC, ddI or d4T) susceptibility, they appear to improve the viral fitness by restoring the nucleotide incorporation efficiency (kpol/Kd) to wild type levels, and partially restoring NRTI excision. 2014 Viruses Introduction HIV A62V;K65R;S68G;A62V;K65R;K65R;S68G 59;64;69;18;23;34;29 63;68;73;22;27;38;33 NRTI;NRTI 97;295 101;299 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Work from our group demonstrated that the efficiency of both these steps of misincorporation are reduced by the K65R mutation; the initial misinsertion showing a decreased catalytic rate, and primer misextension, through decreased nucleotide binding. 2014 Viruses Introduction HIV K65R 112 116 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. APV is a potent inhibitor and efficiently inhibits the activity of PR1 (Figure 1C and D), but some mutations (V32I, I47V and V82I) in PR2 produce natural resistance to APV. 2014 Scientific reports Introduction HIV I47V;V32I;V82I 116;110;125 120;114;129 PR;PR 134;67 137;70 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Collectively these studies provided initial evidence of reduced neuropathogenesis in clade C secondary to the C31S substitution. 2014 Journal of neurovirology Introduction HIV C31S 110 114 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Interestingly, recently reported that the C31S motif substitution of the Tat protein is not conserved ubiquitously in South Africa. 2014 Journal of neurovirology Introduction HIV C31S 42 46 Tat 73 76 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Neuroimaging studies of HIV-infected adolescents and adults in South Africa also reveal abnormalities in the cortical gray and subcortical brain regions, suggesting that despite the reported presence of the Tat C31S substitution, individuals infected with clade C HIV exhibit significant brain abnormalities. 2014 Journal of neurovirology Introduction HIV C31S 211 215 Tat 207 210 HIV infections 24 36 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Numerous subsequent laboratory studies revealed reduced astrogliosis, reduced activation of proinflammatory cytokines, decreased augmentation of tumor necrosis factor (TNF), and less severe cognitive impairment in mice with the C31S substitution. 2014 Journal of neurovirology Introduction HIV C31S 228 232 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. The C31S substitution resulted in reduced monocyte chemotaxis, and was referenced as a potential biological explanation for the lower incidence of HAD reported in clade C. 2014 Journal of neurovirology Introduction HIV C31S 4 8 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. The present study examined this important question among patients infected with clade C inclusive with or without the C31S Tat substitution. 2014 Journal of neurovirology Introduction HIV C31S 118 122 Tat 123 126 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. These results help to explain the high level of cognitive impairment and neuroimaging abnormalities in South Africa but the findings do not explain the high rate of cognitive impairment previously reported in India where the C31S substitution is present in more than 90 percent of cases. 2014 Journal of neurovirology Introduction HIV C31S 225 229 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. To date no study has directly examined cognitive status among individuals based on the presence or absence of the C31S substitution within the same cohort. 2014 Journal of neurovirology Introduction HIV C31S 114 118 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Using virus evolution, we selected for the novel K42E mutation in IN that increased the efficiency of the customized transduction system to ~75% of the level of WT HIV-1. 2014 Molecular therapy. Methods & clinical development Introduction HIV K42E 49 53 IN 66 68 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Now, many mutations are identified, single mutations like G36D/S, V38A/M, Q40H, N42S/T/D/E, N43D/K/S, L44M and L45M have been generally showed to reduce the sensitivity of ENF. 2014 PloS one Introduction HIV G36D;G36S;L44M;L45M;N42D;N42E;N42S;N42T;N43D;N43K;N43S;Q40H;V38A;V38M 58;58;102;111;80;80;80;80;92;92;92;74;66;66 64;64;106;115;90;90;90;90;100;100;100;78;72;72 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The aims of this work is to: 1, explore the changes on energy and structure between wild type and mutation type(N43D) of gp41; 2, explore the role of CHR compensatory mutation S138A by energy and structural analysis; 3, hypothesize mechanisms of drug resistance induced by N43D single mutation and N43D/S138 double mutation. 2014 PloS one Introduction HIV N43D;N43D;N43D;S138A 112;273;298;176 116;277;302;181 gp41 121 125 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, the fitness costs of the T242N and other T cell escape mutations have been exclusively studied in unrelated heterologous viral backbones, in which the presence of unknown compensatory mutations can significantly affect the interpretation of results. 2014 Retrovirology Introduction HIV T242N 34 39 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Moreover, since fitness costs of the T242N mutation have not been studied in transmitted/founder (T/F) viral genomes, it remains unknown how the context of different T/F genomes affect its fitness impact, especially in the cognate T/F viruses from which the T242N mutation was selected or in the transmitted T242N mutants. 2014 Retrovirology Introduction HIV T242N;T242N;T242N 37;258;308 42;263;313 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The T242N mutation in the HLA-B*57/5801-restricted TW10 epitope in Gag p24240-249 (TSTLQEQIGW) has been widely studied for its impact on viral fitness, pathogenesis, and disease progress as well as the repair of its fitness costs by compensatory mutations in heterologous viral backbones. 2014 Retrovirology Introduction HIV T242N 4 9 Gag 67 70 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. To fully understand the impact of the T242N mutation on viral fitness, we now investigated its fitness costs and the compensation in four additional T/F viruses. 2014 Retrovirology Introduction HIV T242N 38 43 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Using an unmodified infectious T/F molecular clone (CH77) from which the T242N was selected in vivo, we previously reported that the T242N mutation had a significant fitness cost in its cognate T/F virus but the fitness loss could be fully repaired by the compensatory mutations in the same TW10 epitope. 2014 Retrovirology Introduction HIV T242N;T242N 73;133 78;138 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Consequently, BI-1001 was unable to promote aberrant multimerization of recombinant A128T IN, whereas it maintained its ability to inhibit IN-LEDGF/p75 binding in vitro. 2014 Retrovirology Introduction HIV A128T 84 89 IN;IN 90;139 92;141 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Here, we have investigated the mechanism of resistance for the H171T IN mutation. 2014 Retrovirology Introduction HIV H171T 63 68 IN 69 71 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Interestingly, crystallographic studies have revealed that BI-1001 is still able to bind A128T IN CCD by maintaining all hydrogen bonding interactions, but that the quinoline ring bridging the two IN subunits was slightly shifted compared with the wild type (WT) protein. 2014 Retrovirology Introduction HIV A128T 89 94 IN;IN 95;197 97;199 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Of these, HIV-1 bearing the single amino acid H171T substitution was found to be one of the most prominent mutations persisting at the highest concentration of BI-D tested. 2014 Retrovirology Introduction HIV H171T 46 51 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Of these, the A128T IN substitution was the most prevalent mutation with HIV-1NL4-3(A128T IN) displaying marked resistance to respective ALLINI compounds. 2014 Retrovirology Introduction HIV A128T;A128T 14;84 19;89 IN;IN 20;90 22;92 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Our findings show that unlike A128T, the H171T IN substitution causes resistance to BI-D by reducing the binding affinity of the inhibitor to IN. 2014 Retrovirology Introduction HIV A128T;H171T 30;41 35;46 IN;IN 47;142 49;144 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Our structural studies have elucidated a previously undescribed role of the His171 side chain for hydrogen bonding with BI-D tert-butoxy ether oxygen, which is compromised upon the H171T substitution. 2014 Retrovirology Introduction HIV H171T 181 186 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Selection of HIV-1 variants in the presence of ALLINI BI-D (Additional file 1: Figure S1), a more potent analog of BI-1001, did not result in the A128T mutation but instead revealed several amino acid changes near the inhibitor binding sites including Y99H, L102F, A/T124D, and H171T. 2014 Retrovirology Introduction HIV A124D;A128T;H171T;L102F;T124D;Y99H 265;146;278;258;265;252 272;151;283;263;272;256 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Since LEDGF/p75 lacks a tert-butoxy moiety, the H171T substitution has minimal effects on IN-LEDGF/p75 binding and accordingly, HIV-1NL4-3(H171T IN), replicated in cells at WT levels. 2014 Retrovirology Introduction HIV H171T;H171T 48;139 53;144 IN;IN 90;145 92;147 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. These findings have uncovered the structural and mechanistic basis for H171T IN resistance to BI-D and are expected to facilitate in the development of second generation ALLINIs with increased potency and decreased potential to evolve drug resistance. 2014 Retrovirology Introduction HIV H171T 71 76 IN 77 79 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. It is also the case of the triple substitutions LQ (K186Q, Q214L, and Q216L) or N (R262A, R263A, and K264H), either impairing IN binding to importin-alpha1 (ref.) or TNPO3 (refs.) and resulting in lack of HIV DNA integration. 2014 Molecular therapy. Nucleic acids Introduction HIV K186Q;K264H;Q214L;Q216L;R262A;R263A 52;101;59;70;83;90 57;106;64;75;88;95 IN 126 128 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Moreover, the surprising hyperintegrative phenotype of a D167H mutant IN is further studied in more detail. 2014 Molecular therapy. Nucleic acids Introduction HIV D167H 57 62 IN 70 72 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Of these mutations, the D64V substitution is the most used in studies with NILV. 2014 Molecular therapy. Nucleic acids Introduction HIV D64V 24 28 25488402 Modulation of HIV protease flexibility by the T80N mutation. CD and tryptophan fluorescence spectroscopy data indicate that there is very little difference between the apo structures of the WT and T80N mutant forms. 2015 Proteins Introduction HIV T80N 137 141 25488402 Modulation of HIV protease flexibility by the T80N mutation. In the earliest MD simulations of the T80N mutant it was noted that there was decreased conformational mobility in the flap regions that open to allow substrate access to the enzymatic site and close over bound compounds . 2015 Proteins Introduction HIV T80N 38 42 25488402 Modulation of HIV protease flexibility by the T80N mutation. The ligand-bound crystal structure of HIVp incorporating the T80N mutation is also essentially unchanged from the WT structure with an rms deviation between all pairs of Calpha atoms of 0.6 A but HIVp containing the T80N mutation is devoid of enzymatic activity and cannot support viral replication . 2015 Proteins Introduction HIV T80N;T80N 61;216 65;220 25488402 Modulation of HIV protease flexibility by the T80N mutation. These results are compared with MD simulations of the WT protein and the T80N variant. 2015 Proteins Introduction HIV T80N 73 77 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. However, the mutation N674D had appeared in the context of virus selected in the presence of CBAs (HHA+2G12), containing not only the N674D mutation in gp41 but also 3 additional N-glycosylation site mutations in gp120 (N160, N339 and N386 -according to HIV-1HXB2 amino acid numbering). 2014 Retrovirology Introduction HIV N674D;N674D 22;134 27;139 gp120;gp41 213;152 218;156 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. A change from a methionine to valine or isoleucine at position 184 (M184V/I) in reverse transcriptase (RT) is the most frequently observed resistance mutation in patients experiencing treatment failure but is only rarely observed in untreated, newly diagnosed individuals using population-based sequencing assays. 2014 Retrovirology Introduction HIV M184I;M184V 68;68 75;75 RT;RT 80;103 101;105 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Accordingly, the M184V variant can be detected as a minority species in recently infected individuals using very sensitive assays, which is suggestive of reversion to wild type. 2014 Retrovirology Introduction HIV M184V 17 22 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Contrary to M184V, the frequently observed RT mutation K103N has a similar prevalence in treated and untreated patients. 2014 Retrovirology Introduction HIV K103N;M184V 55;12 60;17 RT 43 45 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. In addition, diminished transmission efficacy of the M184V variant has been suggested based on mathematical modeling and a macaque SHIV model. 2014 Retrovirology Introduction HIV M184V 53 58 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. K103N has been described to have a modest effect on viral RC, and can persist for years after transmission to a new host. 2014 Retrovirology Introduction HIV K103N 0 5 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. M184V/I causes high level resistance against the nucleoside reverse transcriptase inhibitors lamivudine and emtricitabine, but at the same time considerably decreases the processivity of reverse transcriptase (RT) resulting in a reduced viral replication capacity (RC). 2014 Retrovirology Introduction HIV M184I;M184V 0;0 7;7 NRTI;RT;RT 49;187;210 81;208;212 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The low prevalence of the M184V mutation in therapy-naive individuals may be explained by the reduced RC of this mutant, which can directly impair transmission efficacy and/or lead to reversion of M184V in the new host. 2014 Retrovirology Introduction HIV M184V;M184V 26;197 31;202 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The objective of this study was to investigate the transmission efficacy of the HIV-1 M184V/I RT variants. 2014 Retrovirology Introduction HIV M184I 86 94 RT 94 96 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The presence of K103N causes high levels of resistance against the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine. 2014 Retrovirology Introduction HIV K103N 16 21 NNRTI 67 103 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. These results clearly imply a role for HIV RC in transmission efficacy and provide an additional explanation for the low prevalence of HIV M184V/I in therapy naive individuals. 2014 Retrovirology Introduction HIV M184I;M184V 139;139 146;146 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. We used an HIV transmission model containing primary human DCs to compare the transmission efficacy of HIV harboring M184V/I to wild type HIV. 2014 Retrovirology Introduction HIV M184I;M184V 117;117 124;124 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. When HIV variants harboring M184V are transmitted to a new host, rapid reversion of the M184V variant has been documented (reviewed in). 2014 Retrovirology Introduction HIV M184V;M184V 28;88 33;93 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. With this virus panel, we demonstrated that the M184V/I variants were less efficiently transmitted to CCR5+ Jurkat T cells by both LCs and DCs, which was due to the lower RC of the M184V/I variants in both DC subsets. 2014 Retrovirology Introduction HIV M184I;M184I;M184V;M184V 48;181;48;181 55;188;55;188 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. An analysis of the database facilitated the determination of a previously uncharacterized, SQV/RTV resistant variant, Gly48Thr/Leu89Met (PRG48T/L89M). 2015 Biochemistry Introduction HIV G48T;L89M;L89M 118;127;144 126;135;148 PR 137 139 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. by showing that disulfide cross-links (Gly16Cys/Leu38Cys) that exert a conformational restraint on the hydrophobic core compromise protease activity, and that activity can be largely restored through reduction of the cross-links. 2015 Biochemistry Introduction HIV G16C;G16L;L38C 39;39;48 47;47;56 PR 131 139 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Gly48Val, a primary mutation, occurs in response to SQV treatment and less often from IDV and LPV treatment- and confers high-level resistance to SQV, intermediate-level resistance to ATV, and low-level resistance to NFV, IDV, and LPV.- Gly48Met occurs in patients who have received multiple PIs and results in a similar resistance profile as Gly48Val.- Gly48Ala/Ser/Thr/Gln/Leu are extremely rare PR mutations that occur primarily in viruses containing multiple PI-resistance mutations and appear to have similar but weaker effects on PI susceptibility than do Gly48Val and Gly48Met. 2015 Biochemistry Introduction HIV G48A;G48M;G48M;G48Q;G48S;G48T;G48V;G48V;G48V 354;237;575;354;354;354;0;343;562 378;245;583;378;378;378;8;351;570 PI;PI;PI;PR 292;463;536;398 295;465;538;400 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Here we report on the cocrystal structure of HIV-1 PR with the double mutation Gly48Thr/Leu89Met bound with saquinavir (SQV) (PRG48T/L89M-SQV) in the active site cavity. 2015 Biochemistry Introduction HIV G48M;G48T;L89M;L89M 79;79;88;133 87;87;96;137 PR;PR 51;126 53;128 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Leu89Val, a secondary mutation, is an accessory mutation and is located outside the active site in the hydrophobic core of PR and occurs in response to treatment with IDV, NFV, FPV, and DRV. 2015 Biochemistry Introduction HIV L89V 0 8 PR 123 125 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The side chains of 7 of the 19 residues in the hydrophobic core of PRG48T/L89M-SQV as defined by Foulkes-Murzycki et al. 2015 Biochemistry Introduction HIV L89M 74 78 PR 67 69 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. This enhances the deleterious effects of the primary mutation, Gly48Thr, on inhibitor binding. 2015 Biochemistry Introduction HIV G48T 63 71 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. We propose that the modified vdw interactions result in a defective hydrophobic sliding mechanism, leading to the inability of PRG48T/L89M-SQV to achieve a fully closed conformation, thus resulting in an expanded active site and weaker flap interactions. 2015 Biochemistry Introduction HIV L89M 134 138 PR 127 129 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. A recent study found good correlation of Roche 454 sequencing for K103N and Y181C, when screening PMTCT exposed children (less than 2 years of age) prior to cART initiation. 2015 Journal of clinical virology Introduction HIV K103N;Y181C 66;76 71;81 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. In the present study, we examined the ability of the Env gp120 with W427S of an HIV-1 primary R5 strain in Ab elicitation and in Tfh amount, function and memory in immunized BALB/c mice to try to clarify the Tfh responses and immune memory induced by Env immunization to facilitate the understanding about its weak immunogenicity. 2014 PloS one Introduction HIV W427S 68 73 gp120;Env;Env 57;53;251 62;56;254 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. It has been found that the CD4BS core including residues 425-430 overlaps a B cell superantigen site and we investigated whether the modified Env with W427S, aborting CD4 binding but maintaining the binding ability to CD4BS Abs, could reduce interference of superantigen property. 2014 PloS one Introduction HIV W427S 151 156 Env 142 145 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. An amino acid substitution at this position (Y115F) for HIV-1 RT has also been associated with low-level resistance to several nucleoside reverse transcriptase inhibitors (NRTI). 2015 Antiviral research Introduction HIV Y115F 45 50 NRTI;NRTI;RT 127;172;62 159;176;64 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. Y115F) decreases RT's ability to discriminate rNTPs from dNTPs, which warrants further pre-steady state kinetic investigation. 2015 Antiviral research Introduction HIV Y115F 0 5 RT 17 19 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. An increased free energy for the polar solvation contributes to the drug resistance for the V32I mutant to amprenavir. 2015 Journal of molecular graphics & modelling Introduction HIV V32I 92 96 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. However, M46L mutation in the flexible flap does not directly contact with an inhibitor bound in the active site cleft, while the main chain atoms of Met46 may form H-bonds with substrate analogs. 2015 Journal of molecular graphics & modelling Introduction HIV M46L 9 13 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. In the current study, to explore the drug resistance behavior of the two mutants V32I and M46L HIV-1-pr to the inhibitor TMC114 and to differentiate the binding affinities of the double TMC114 bound complex (2T) from that of single TMC114 bound complex (1T), MD simulations have been performed for five different inhibitor bound complexes: WT-1T, V32I-1T and M46L-1T HIV-1-pr as well as for V32I-2T and M46L-2T HIV-1-pr. 2015 Journal of molecular graphics & modelling Introduction HIV M46L;M46L;M46L;V32I;V32I;V32I 90;359;403;81;347;391 94;363;407;85;351;395 PR;PR;PR 101;373;417 103;375;419 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. It was found that, the mutations D30N and I50V results in the drug resistance to TMC114; however the changes due to mutations V82A, I84V and L90M are well adapted by TMC114. 2015 Journal of molecular graphics & modelling Introduction HIV D30N;I50V;I84V;L90M;V82A 33;42;132;141;126 37;46;136;145;130 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Mutations V32I and M46L are considered as two of the most multi-drug-resistant mutations of the HIV-1-pr drug resistance to inhibitors in clinical use. 2015 Journal of molecular graphics & modelling Introduction HIV M46L;V32I 19;10 23;14 PR 102 104 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Our previous studies on binding Gibbs free energies for WT, I50V single mutant and I50L/A71V double mutant showed that I50V decreases the binding affinity for TMC114, while the double mutant I50L/A71V increases the binding affinity and may be well adapted to accommodate the TMC114 in the active site. 2015 Journal of molecular graphics & modelling Introduction HIV A71V;A71V;I50L;I50L;I50V;I50V 88;196;83;191;60;119 92;200;87;195;64;123 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. performed MD simulation studies combined with MM-PBSA to investigate the binding energies of TMC114 to D30N and I50V mutants. 2015 Journal of molecular graphics & modelling Introduction HIV D30N;I50V 103;112 107;116 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The average flap-flap distance and flap tip - active site distances are believed to be longer for the M46L-2T HIV-1-pr complex as compare to the WT-1T and V32I-2T complexes suggesting a higher mobility in M46L-2T, possibly making the active site volume larger. 2015 Journal of molecular graphics & modelling Introduction HIV M46L;M46L;V32I 102;205;155 106;209;159 PR 116 118 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The resistance of inhibitor amprenavir, which is an analog of TMC114 to mutant V32I, I50V and I84V with an increase in the energetic contribution from the van der Waals interactions, was also explained in another study by Kar et al. 2015 Journal of molecular graphics & modelling Introduction HIV I50V;I84V;V32I 85;94;79 89;98;83 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Therefore M46L mutation can affect the binding affinity indirectly either by reducing the hydrophobic interactions or by strengthening interactions with a substrate. 2015 Journal of molecular graphics & modelling Introduction HIV M46L 10 14 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. They found that, loss of H-bonds between Asp30 and TMC114 drives the drug resistance in D30N, while for I50V it is the increased polar solvation energies between TMC114 and two residues Asp30' and Val50'. 2015 Journal of molecular graphics & modelling Introduction HIV D30N;I50V 88;104 92;108 Asp;Asp 41;186 44;189 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. utilized the crystallographic study to analyze the effectiveness of TMC114 to HIV-1-pr, with highly drug resistant mutants D30N, I50V, V82A, I84V, and L90M. 2015 Journal of molecular graphics & modelling Introduction HIV D30N;I50V;I84V;L90M;V82A 123;129;141;151;135 127;133;145;155;139 PR 84 86 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. V32I mutation is located in the active site region, which can directly contribute to the drug resistance by unfavorable interactions with an inhibitor because isoleucine is larger than valine. 2015 Journal of molecular graphics & modelling Introduction HIV V32I 0 4 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. A previous study investigated the role of the PR M36I polymorphism on the interaction with the inhibitor nelfinavir. 2014 BMC genomics Introduction HIV M36I 49 53 PR 46 48 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Among these polymorphisms, M36I is widely found in non-B proteases; some authors suggest that it might be considered a genetic marker for HIV-1 group M non-B subtypes. 2014 BMC genomics Introduction HIV M36I 27 31 PR 57 66 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Binding free energies calculated from the MD trajectories with MM-PBSA revealed that for the majority of complexes, the M36I proteases have a decreased affinity against the substrates when compared to the WT (B-subtype) PR. 2014 BMC genomics Introduction HIV M36I 120 124 PR;PR 125;220 134;222 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. designed a PR variant (A28S/D30F/G48R) with altered specificity for one of the substrate-cleavage sites, showing that understanding protein-protein specific contacts one is able to engineer a more stable complex. 2014 BMC genomics Introduction HIV A28S;D30F;G48R 23;28;33 27;32;37 PR 11 13 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Herein, we performed a set of molecular dynamics simulations (50 ns) to better understand the interactions between PR (B-subtype or M36I) and six different natural substrates. 2014 BMC genomics Introduction HIV M36I 132 136 PR 115 117 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Nonetheless, there are two exceptions: the complexes with RT-RH, with equivalent affinity, and the RH-IN substrate, with an increased affinity for the M36I PR. 2014 BMC genomics Introduction HIV M36I 151 155 IN;PR;RT 102;156;58 104;158;60 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Therefore, there is still a need for structural studies evaluating the impact of the PR M36I polymorphism regarding its interaction with natural substrates. 2014 BMC genomics Introduction HIV M36I 88 92 PR 85 87 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. A worrying trend is the increased prevalence of non-nucleoside RT inhibitor (NNRTI) related mutations in newly diagnosed patients, as single NNRTI mutations, such as the frequently observed K103N mutation, can result in high levels of resistance against first generation NNRTIs. 2014 Retrovirology Introduction HIV K103N 190 195 NNRTI;NNRTI;NNRTI;RT 77;141;271;63 82;146;277;65 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Especially thymidine analogue mutations (TAMs) M41L and T215 variants, that have been selected by drugs extensively used in the past, are often observed in newly diagnosed patients. 2014 Retrovirology Introduction HIV M41L 45 51 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In protease, M46I/L and L90M are the most frequently observed TDRM. 2014 Retrovirology Introduction HIV L90M;M46I;M46L 24;13;13 28;19;19 PR 3 11 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Indeed, follow-up of untreated individuals diagnosed with a drug resistant HIV variant revealed that certain mutations with a detrimental effect on the viral RC, such as M184V in RT, after transmission to a new host often revert rapidly in the plasma. 2014 Retrovirology Introduction HIV M184V 170 175 RT 179 181 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. When present in combination with other protease drug resistance mutations, both M46I/L and L90M are related to reduced susceptibility to several protease inhibitors (PIs). 2014 Retrovirology Introduction HIV L90M;M46I;M46L 91;80;80 95;86;86 PR;PR;PI 39;145;166 47;153;169 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. One good example of this is the V106M polymorphism in the RT of subtype C viruses inducing resistance to NNRTIs. 2015 AIDS research and human retroviruses Introduction HIV V106M 32 37 NNRTI;RT 105;58 111;60 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. For example, we have demonstrated that mutating tyrosine470 to histidine of hDAT attenuates Tat-mediated inhibition of DA uptake and leads to alteration of transporter conformational transitions. 2015 Journal of neuroimmune pharmacology Introduction HIV Y470H 48 72 Tat 92 95 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. In the current study, we investigated the role of additional substitutions at Tyr470 and other predicted potential Tat binding residues, Tyr88 and Lys92 of hDAT in Tat-induced decrease of DA translocation by generating points mutations Tyr470F (Y470F-hDAT), Tyr470A-hDAT (Y470A-hDAT), Tyr88Phe (Y88F-hDAT), Lys92Met (K92M-hDAT) and assessing their variability in function, surface expression, interaction with ligands and underlying mechanism for these alterations. 2015 Journal of neuroimmune pharmacology Introduction HIV K92M;K92M;Y470A;Y470A;Y470D;Y470Delta;Y470F;Y470H;Y470T;Y88F;Y88F 307;317;272;258;258;258;245;258;258;285;295 315;321;277;264;264;264;250;264;264;293;299 Tat;Tat 115;164 118;167 25617150 Synthesis, HIV-1 RT inhibitory, antibacterial, antifungal and binding mode studies of some novel N-substituted 5-benzylidine-2,4-thiazolidinediones. Thus, the therapeutic efficacy of NNRTIs is mainly restricted due to development of viral resistance to NNRTIs associated with mutations that include K103N, L100I and Y188L, and with the development of second generation NNRTIs, the search for a more suitable NNRTI, which blocks the replication of all existing resistant viral strains and retains potency for longer periods of time by modifying the existing drug classes or by incorporating appropriate substitutions in the newer chemical scaffolds, according to the pharmacophoric requirements using multi-disciplinary approaches is the call of the day. 2015 Daru Introduction HIV K103N;L100I;Y188L 150;157;167 155;162;172 NNRTI;NNRTI;NNRTI;NNRTI 34;104;220;259 40;110;226;264 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. have already emphasized the context by which PMTCT led to resistance mutations induced by nevirapine (NVP; V8IV, K103N, V179E, and Y181C). 2015 Global health action Introduction HIV K103N;V179E;V8I;V8V;Y181C 113;120;107;107;131 118;125;111;111;136 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. A third study showed a K65R prevalence of 23%, which is substantially lower compared to the other two studies. 2015 PloS one Introduction HIV K65R 23 27 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Of particular concern, the K65R mutation leads to cross-resistance to most of the nucleoside reverse transcriptase inhibitors (NRTIs) and therefore jeopardizes the effectiveness of second line regimens. 2015 PloS one Introduction HIV K65R 27 31 NRTI;NRTI 82;127 114;132 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. One study demonstrated that more than 65% of the TDF exposed patients developed the K65R mutation, whereas the second study found K65R to be prevalent in 46% of the patients treated with TDF. 2015 PloS one Introduction HIV K65R;K65R 84;130 88;134 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Both amino acid substitutions confer increased affinity for the template-primer, while N348I reduces the association rate of the RT and nevirapine. 2015 Nucleic acids research Introduction HIV N348I 87 92 RT 129 131 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. During (+)-strand DNA synthesis, nevirapine and efavirenz facilitate the premature removal of the PPT by favoring its binding in a polymerase-independent orientation, although it has been shown that the presence of N348I could attenuate the effects of nevirapine. 2015 Nucleic acids research Introduction HIV N348I 215 220 Pol 131 141 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Furthermore, HIV-1 clones carrying RT mutations N348I and T369I show high-level resistance to both drugs and moderate resistance to efavirenz, although the presence of both mutations confers a severe fitness defect. 2015 Nucleic acids research Introduction HIV N348I;T369I 48;58 53;63 RT 35 37 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. K103N or Y181C) (reviewed in). 2015 Nucleic acids research Introduction HIV Y181C;K103N 9;0 14;5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. N348I has a detrimental effect on the RNase H activity of the RT. 2015 Nucleic acids research Introduction HIV N348I 0 5 RT 62 64 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Our study provides mechanistic insight into how the double-mutant N348I/T369I in HIV-1 RT could affect PPT removal and RNase H cleavage specificity in the absence or presence of NNRTIs. 2015 Nucleic acids research Introduction HIV N348I;T369I 66;72 71;77 NNRTI;RT 178;87 184;89 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Specifically, mutations away from the NNRTI binding pocket such as N348I, T369I or V and A376S confer low-to-moderate levels of resistance to nevirapine and delavirdine in phenotypic assays carried out with recombinant HIV-1. 2015 Nucleic acids research Introduction HIV A376S;N348I;T369I 89;67;74 94;72;79 NNRTI 38 43 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The increased prevalence of N348I and A376S in treated patients has been related to previous exposure to nevirapine while the presence of those mutations has been associated with an increased risk of virological failure. 2015 Nucleic acids research Introduction HIV A376S;N348I 38;28 43;33 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. In the presence of D30N/N88D mutations in the protease, the coevolutionary mutation LP1'F at the p1-p6 cleavage site provides a better fit within the dynamic substrate envelope. 2015 Evolutionary applications Introduction HIV D30N;N88D 19;24 23;28 Env;PR;Gag 168;46;100 176;54;102 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Similarly, in NC-p1, the compensatory AP2V substitution occurs in the presence of V82A mutation in the protease. 2015 Evolutionary applications Introduction HIV V82A 82 86 PR;NC 103;14 111;16 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Two examples of this evolutionary interplay between substrate and enzyme are the coevolution of p1-p6 substrate cleavage site with D30N/N88D protease mutations (Bally et al.) and the coevolution of NC-p1 substrate cleavage site with V82A protease mutation (Doyon et al.). 2015 Evolutionary applications Introduction HIV D30N;N88D;V82A 131;136;233 135;140;237 PR;PR;NC;Gag 141;238;198;99 149;246;200;101 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Although flexible diarylpyrimidine inhibitors (DAPYs) etravirine and rilpivirine maintain potency over Y181C variants, several first-generation inhibitors, such as nevirapine and efavirenz, suffer from ~63- and 12-fold changes in potency against RT (Y181C) compared with RT (WT). 2015 Journal of medicinal chemistry Introduction HIV Y181C;Y181C 103;250 108;255 RT;RT 246;271 248;273 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Among several variants identified in the clinic, mutations at the Y181 position are highly prevalent and exist as single variants, such as RT (Y181I), RT (Y181V), and RT (Y181C), as well as the double variant RT (K103N/Y181C). 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C;Y181I;Y181V 213;171;219;143;155 218;176;224;148;160 RT;RT;RT;RT 139;151;167;209 141;153;169;211 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. As observed in all six structures, the protein backbone interaction with Lys/Asn103 is retained with the uracil. 2015 Journal of medicinal chemistry Introduction HIV K103N 77 83 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Changes in potency against the RT (K103N/Y181C) variant are dramatic as well for nevirapine and efavirenz, as observed in the decrease in potency by 625- and 1176-fold, respectively. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C 35;41 40;46 RT 31 33 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Despite the loss of a pi-pi stacking interaction caused by the Y181C mutation, crystal structures of RT (WT), RT (Y181C), and RT (K103N/Y181C) in complex with 2 reveal that the inhibitor maintains the same conformation. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C;Y181C 130;63;114;136 135;68;119;141 PI;PI;RT;RT;RT 22;25;101;110;126 24;27;103;112;128 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Encouragingly, the elimination of the 5-Cl from the catechol ring significantly improves both compound solubility and performance against Y181C and K103N/Y181C resistant variants of RT. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 148;138;154 153;143;159 RT 182 184 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In addition to being highly soluble, the compound retains better potency against both the Y181C and K103N/Y181C variants of RT. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 100;90;106 105;95;111 RT 124 126 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In addition, the uracil ring of 1 in the RT (Y181C) and RT (K103N/Y181C) structures is slightly rotated and prevents the formation of key hydrogen bonds that were previously formed in the RT (WT):1 crystal structure. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 60;45;66 65;50;71 RT;RT;RT 41;56;188 43;58;190 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In antiviral assays, EC50 values increase from 55 pM to 49 nM for viral strains containing RT with the single Y181C mutation and 220 nM for viral strains containing double mutation K103N/Y181C. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 181;110;187 186;115;192 RT 91 93 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In contrast to compound 1, the modified analogue maintains activity for wild-type, Y181C, and K103N/Y181C RT variants in the low- to midnanomolar range. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 94;83;100 99;88;105 RT 106 108 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Noticeably, 1 shifts in the RT (Y181C) and RT (K103N/Y181C) structures because of the elimination of a pi-pi stacking interaction between Tyr181 (replaced with Cys181) and the catechol aryl ring. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 47;32;53 52;37;58 PI;PI;RT;RT 103;106;28;43 105;108;30;45 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. There are several research groups that use a multidisciplinary approach in designing new NNRTIs with better pharmacological and resistance profiles.- Previously, we have reported the computational design, synthesis, antiviral activity, and wild-type crystal structures for potent analogues of wild-type RT known as the catechol diethers.- Although our leading catechol diether derivative compound 1 has picomolar potency against the wild-type RT enzyme, potency is lost for the single Y181C and K103N/Y181C variants. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 495;485;501 500;490;506 NNRTI;RT;RT 89;303;443 95;305;445 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. This analogue was synthesized and evaluated for solubility and activity against HIV-1 virus containing wild-type, Y181C, and K103N/Y181C variants of RT. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 125;114;131 130;119;136 RT 149 151 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. This dramatic change in potency between wild-type and mutant forms of the RT enzyme warrants the investigation of RT (Y181C) and RT (K103N/Y181C) structures in complex with our leading catechol diether compound. 2015 Journal of medicinal chemistry Introduction HIV K103N;Y181C;Y181C 133;118;139 138;123;144 RT;RT;RT 74;114;129 76;116;131 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. To elucidate the interactions maintained or lost with the mutant enzymes, we determined additional crystal structures of RT (WT), RT (Y181C), and RT (K103N/Y181C) in complex with compound 2 as well as crystal structures of RT (Y181C) and RT (K103N/Y181C) in complex with compound 1. 2015 Journal of medicinal chemistry Introduction HIV K103N;K103N;Y181C;Y181C;Y181C;Y181C 150;242;134;156;227;248 155;247;139;161;232;253 RT;RT;RT;RT;RT 121;130;146;223;238 123;132;148;225;240 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Effects of the A163X are partially compensated for by a subsequent S165N substitution. 2015 Vaccine Introduction HIV A163X;S165N 15;67 20;72 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. In subjects with presenting alleles, chronic infection is dominated by the HLA-B*57-restricted KF11 response and consequent A146X escape mutations that impair virus replicative ability. 2015 Vaccine Introduction HIV A146X 124 129 HIV infections 37 54 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Reversion of the transmitted T242N to wild-type sequence implies that this mutation affects virus fitness. 2015 Vaccine Introduction HIV T242N 29 34 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. The TW10 response dominates in acute HIV infection of HLA B*57 and B*5801 subjects yielding T242N mutations that are associated with lower viral loads over time. 2015 Vaccine Introduction HIV T242N 92 97 HIV infections 37 50 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Consistent with the ability of silent mutations to reverse RT pausing observed in biochemical assays due to the TAMs D67N/K70R, we demonstrate that K65K and K66K decrease the frequency of deleterious insertion and deletion mutations. 2015 Nucleic acids research Introduction HIV D67N;K65K;K66K;K70R 117;148;157;122 121;152;161;126 RT 59 61 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Emergence of drug-resistant viruses containing the TAMs D67N/K70R in these subtypes creates a run of eight A nucleotides in the RNA template between nucleotides 2742 and 2749 (relative to HXB2) of RT. 2015 Nucleic acids research Introduction HIV D67N;K70R 56;61 60;65 RT 197 199 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. In addition to nonsynonymous or 'amino acid changing' TAMs, we have previously shown that synonymous RT mutations, namely K65K and K66K, in HIV-1 subtype B are more prevalent in cART-experienced compared to naive individuals and are strongly co-selected with TAMs. 2015 Nucleic acids research Introduction HIV K65K;K66K 122;131 126;135 RT 101 103 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. In this study, we investigated whether K65K and K66K affect viral fitness as well as susceptibility to RT inhibitors in the context of TAMs. 2015 Nucleic acids research Introduction HIV K65K;K66K 39;48 43;52 RT 103 105 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. L210W and K219Q/E that potentiate ZDV resistance in the context of other TAMs. 2015 Nucleic acids research Introduction HIV K219E;K219Q;L210W 10;10;0 17;17;5 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Possible advantages to viruses harboring K65K or K66K are that they increase fitness of HIV-1 subtype B strains and/or decrease their susceptibility to antiviral drugs. 2015 Nucleic acids research Introduction HIV K65K;K66K 41;49 45;53 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. The emergence of the K65K/K66K silent mutations during drug therapy supports the notion that these mutations confer a replicative advantage. 2015 Nucleic acids research Introduction HIV K65K;K66K 21;26 25;30 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. The presence of the K65K or K66K silent mutations disrupts this homopolymeric A region, and we have demonstrated that these mutations alleviate recombinant HIV-1 RT pausing during cDNA synthesis of this region in vitro, although the impact of our biochemical findings on HIV-1 replication is unknown. 2015 Nucleic acids research Introduction HIV K65K;K66K 20;28 24;32 RT 162 164 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. These polymorphisms are reported to be associated with a more rapid selection of the K65R TFV-resistance mutation in HIV-1 subtype C compared to subtype B. 2015 Nucleic acids research Introduction HIV K65R 85 89 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. This increased selection of K65R is mediated by a template-dependent dislocation mechanism during plus-strand DNA synthesis occurring on a homopolymeric run of six A-nucleotides at RT codons 63-65. 2015 Nucleic acids research Introduction HIV K65R 28 32 RT 181 183 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Amino acid sequence alignments of the polymerase domains of SFVmac and HIV-1 revealed that the SFVmac AZT resistance mutations do not correspond to the ones obtained with highly AZT-resistant HIV-1 RT (M41L, D67N, K70R, T215Y/F and K219Q/E). 2015 Retrovirology Introduction HIV D67N;K219E;K219Q;K70R;M41L;T215F;T215Y 208;232;232;214;202;220;220 212;239;239;218;206;227;227 Pol;RT 38;198 48;200 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Comparison of the AZT resistance mutations selected in HIV-1 and SFVmac shows that in SFVmac no exchange to an aromatic amino acid homologous to T215Y/F occurs. 2015 Retrovirology Introduction HIV T215F;T215Y 145;145 152;152 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In HIV-1 the amino acid exchange T215Y/F is crucial for binding of ATP in the AZT resistant mutant RT. 2015 Retrovirology Introduction HIV T215F;T215Y 33;33 40;40 RT 99 101 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In SFVmac PR-RT four amino acid exchanges (K211I, I224T, S345T, E350K) are necessary to confer high resistance against AZT. 2015 Retrovirology Introduction HIV E350K;I224T;K211I;S345T 64;50;43;57 69;55;48;62 PR;RT 10;13 12;15 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. The aromatic amino acid exchange T215F/Y in the resistant protein allows binding of ATP in site II and the formation of pi-pi stacking interactions with the adenine ring of ATP, necessary for AZTMP excision. 2015 Retrovirology Introduction HIV T215F;T215Y 33;33 40;40 PI;PI 120;123 122;125 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. We have shown previously that the amino acid exchange I224T is important for viral fitness but not for AZT resistance per se. 2015 Retrovirology Introduction HIV I224T 54 59 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. The mutation principally responsible for this protective effect is the above-mentioned HLA-B*81:01-driven T186S variant that fails to yield replicating virus stocks in studies of C clade virus. 2015 Retrovirology Introduction HIV T186S 106 111 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Here we investigate the impact of the I559P change on the conformation and function of the membrane-anchored Env from the primary HIV-1BG505 strain, from which the crystallized SOSIP.664 Env trimers were derived. 2015 PloS one Introduction HIV I559P 38 43 Env;Env 109;187 112;190 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P change was found to stabilize soluble SOS gp140 trimers, and the I559P alteration has been combined with the SOS disulfide bond and deletion of the membrane-proximal gp41 region to produce soluble gp140 SOSIP.664 glycoproteins. 2015 PloS one Introduction HIV I559P;I559P 4;75 9;80 gp140;gp140;gp41 52;207;176 57;212;180 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. To attempt to destabilize the pre-hairpin intermediate and produce Envs in the mature, unliganded state, the helix-breaking isoleucine-to-proline change (I559P) has been introduced into the gp41 ectodomain. 2015 PloS one Introduction HIV I559P 154 159 gp41;Env 190;67 194;71 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. We also investigate the conformation of the gp120 core in the HIV-1BG505 Env by studying the phenotypes of a mutant, S375W, that predisposes gp120 to assume the CD4-bound state. 2015 PloS one Introduction HIV S375W 117 122 gp120;gp120;Env 44;141;73 49;146;76 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. Finally, because the mechanisms of T cell induction are unknown, but could be dose dependent, could involve antigen-presentation through non-classical pathways that are independent of viral replication, and because persons receiving PrEP may be exposed to HIV variants with drug-resistance mutations, we evaluated the virus-specific responses in animals exposed to a replication-impaired virus with a K65R mutation, given at a higher dose than the wild type virus. 2015 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K65R 401 405 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Among the NNRTI drug mutation, K103N, Y181C and G190A are the most common mutation associated with resistance to NVP. 2014 AIDS research and therapy Introduction HIV G190A;K103N;Y181C 48;31;38 53;36;43 NNRTI 10 15 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Even in the patients before ART, Low frequencies of K103N and Y181C are significantly associated with an increased risk of virologic failure. 2014 AIDS research and therapy Introduction HIV K103N;Y181C 52;62 57;67 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In this essay, we retrospectively studied the development of K103N, Y181C and G190A in long-term ART. 2014 AIDS research and therapy Introduction HIV G190A;K103N;Y181C 78;61;68 83;66;73 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In vitro study, K103N, Y181C and G190A could not provide significant fitness reduction to HIV viruses, variant with these mutations had similar viral replication fitness with the wild type variant. 2014 AIDS research and therapy Introduction HIV G190A;K103N;Y181C 33;16;23 38;21;28 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. All these data suggest that the G118R substitution is most characteristic for non-B subtypes of HIV-1 and that the presence of this substitution can lead to patient insensitivity to all IN inhibitors approved for therapeutic use. 2015 Acta naturae Introduction HIV G118R 32 37 IN 186 188 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. However, investigation of the DTG effect on HIV-1 isolates from patients insensitive to RAL and EVG showed that Q148H/K/R substitutions in the integrase structure lead to some resistance to DTG. 2015 Acta naturae Introduction HIV Q148H;Q148K;Q148R 112;112;112 121;121;121 IN 143 152 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. However, only two substitutions, G118R and R263K, proved to be responsible for the virus resistance to DTG . 2015 Acta naturae Introduction HIV G118R;R263K 33;43 38;48 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. In most cases, this mutation occurs in combination with secondary mutations, most frequently G140S/A and E138K/A. 2015 Acta naturae Introduction HIV E138A;E138K;G140A;G140S 105;105;93;93 112;112;100;100 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. In this study we continued the investigation of the role of drug resistance mutations and meticulously compared the effect of the primary mutation Q148K and the secondary mutations E138K and G140S on the activity of INA and INB. 2015 Acta naturae Introduction HIV E138K;G140S;Q148K;E138K;G140S;Q148K 182;192;148;181;191;147 187;197;153;186;196;152 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It is important to note that this virus isolate, containing the G118R substitution in the IN gene, was resistant not only to RAL, but also to EVG and DTG. 2015 Acta naturae Introduction HIV G118R 64 69 IN 90 92 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Moreover, the secondary substitution E138K had a compensatory effect on INB only. 2015 Acta naturae Introduction HIV E138K 37 42 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Mutations Q148H/R/K lead to RAL- and EVG-resistance in different HIV-1 subtypes. 2015 Acta naturae Introduction HIV Q148H;Q148K;Q148R 10;10;10 19;19;19 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Secondary and tertiary mutations (G140A/C/S, L74I and E138A/K/T) further enhance the resistance. 2015 Acta naturae Introduction HIV E138A;E138K;E138T;G140A;G140C;G140S;L74I 54;54;54;34;34;34;45 63;63;63;43;43;43;49 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Substitution G118R slightly reduced the efficiency of IN inhibition by RAL and EVG, this effect was more pronounced in the case of INB, and did not affect the sensitivity of INs to XZ-259. 2015 Acta naturae Introduction HIV G118R 13 18 IN;IN 54;174 56;177 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The fact that the G118R mutation is associated with the lack of sensitivity to RAL in patients infected with the CRF02_A/G strain has recently been demonstrated. 2015 Acta naturae Introduction HIV G118R 18 23 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The G118R substitution reduced the efficiency of 3'-processing for both integrases by 5 times, but it differently affected the enzymes of different strains in the strand transfer reaction: INA activity decreased more significantly than INB activity. 2015 Acta naturae Introduction HIV G118R 4 9 IN 72 82 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The Q148K mutation dramatically decreased the activity of enzymes of both viral subtypes in both reactions: 3'-processing and strand transfer. 2015 Acta naturae Introduction HIV Q148K 4 9 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The same study demonstrated that the E138K mutation was a secondary compensatory substitution for G118R. 2015 Acta naturae Introduction HIV E138K;G118R 37;98 42;103 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. This decrease was partially restored by the secondary mutations E138K and G140S. 2015 Acta naturae Introduction HIV E138K;G140S 64;74 69;79 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Thus, in vitro selection of DTG-resistant strains of HIV-1 subtypes B, C, and A/G demonstrated that only the R263K substitution was common to all subtypes; the G118R substitution was found only in the subtypes A/G and C . 2015 Acta naturae Introduction HIV G118R;R263K 160;109 165;114 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Variants containing a number of amino acid substitutions in IN (H51Y, L101I, G118R, T124A, S153F/Y, R263K) were found during selection of HIV-1 strains resistant to DTG in a lymphocytes culture . 2015 Acta naturae Introduction HIV G118R;H51Y;L101I;R263K;S153F;S153Y;T124A 77;64;70;100;91;91;84 82;68;75;105;98;98;89 IN 60 62 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. We also described the activity of the INA mutants containing the primary G118R substitution and compensatory E138K substitution for the first time. 2015 Acta naturae Introduction HIV E138K;G118R 109;73 114;78 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. We characterized the catalytic activity of INA and its variants containing two major combinations of RALand EVG-resistance mutations: E92Q, V151I, N155H, G163R, L74M (mutant 1), and Q148K, E138K, G140S (mutant 2) . 2015 Acta naturae Introduction HIV E138K;E92Q;G140S;G163R;L74M;N155H;Q148K;V151I 189;134;196;154;161;147;182;140 194;138;201;159;165;152;187;145 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. XZ- 259 effectively inhibited the RAL- and EVG-resistant IN forms containing substitution Q148K. 2015 Acta naturae Introduction HIV Q148K 90 95 IN 57 59 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. indicated that the small structure difference of APV and DRV inhibitors lead to apparently different binding affinities towards WT HIV-1 PR and its two multi-drug-resistant (MDR) variants, namely Flap+ (L10I/G48V/I54V/V82A) and Act (V82T/I84V). 2015 Scientific reports Introduction HIV G48V;I54V;L10I;V82A;I84V;V82T 208;213;203;218;238;233 212;217;207;222;242;237 PR 137 139 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. Kinetic experiments show that the L90M, G48V, and L90M/G48V variants could reduce the binding affinity of inhibitors, which is caused by an increase in dissociation rates. 2015 Scientific reports Introduction HIV G48V;G48V;L90M;L90M 40;55;34;50 44;59;38;54 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. reported that the protease variant with mutation sites in 80 s loops (V82F/I84V) shows more frequent and rapid flap curling than wild-type (WT) HIV-1 PR does. 2015 Scientific reports Introduction HIV I84V;V82F 75;70 79;74 PR;PR 18;150 26;152 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. Similarly, the I50V mutation in flap regions selected by APV shows more flexible flaps, and single mutation distant from flap regions such as L63P or L10I can increase the flexibility of flap regions as well. 2015 Scientific reports Introduction HIV I50V;L10I;L63P 15;150;142 19;154;146 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. The detailed analysis reveals the origin of the amplified structural flexibility of the Act variant: the hydrophobic interactions between flaps and 80 s (80's) loop residues (mainly I50-I84' and I50'-I84) along with the hydrophobic interactions between the two flaps play important roles in maintaining the closed conformation of HIV-1 PR; the double mutation of the 80 s (80's) loop residues (V82T/I84V) weakens the hydrophobic interactions between flap and 80 s (80's) loop regions and thus destabilize the closed conformation. 2015 Scientific reports Introduction HIV I84V;V82T 399;394 403;398 PR 336 338 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. K65R mutation is associated with resistance to all NRTIs except zidovudine (AZT); M184V confers resistance to abacavir (ABC), emtricitabine (FTC), and lamivudine (3TC), whereas Y181C mutation confers resistance to all NNRTIs. 2015 Molecules (Basel, Switzerland) Introduction HIV M184V;Y181C;K65R 82;177;0 87;182;4 NNRTI;NRTI 218;51 224;56 26166629 Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. A methyl group is expected to better fill the space vacated upon the Tyr181Cys exchange than a fluorine. 2015 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 69 78 26166629 Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. Assays tested activity against wild-type HIV-1 and the most common clinically observed viral variants, which contain Tyr181Cys (Y181C) and Lys103Asn (K103N) point mutations in the reverse transcriptase enzyme. 2015 Bioorganic & medicinal chemistry letters Introduction HIV K103N;K103N;Y181C;Y181C 139;150;117;128 148;155;126;133 RT 180 201 26166629 Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. Overall, 3 is among the best examples with EC50 values of 0.31, 46, and 24 nM towards wild-type HIV-1, and virus containing the Y181C mutation and the particularly challenging K103N/Y181C double variant. 2015 Bioorganic & medicinal chemistry letters Introduction HIV K103N;Y181C;Y181C 176;128;182 181;133;187 26166629 Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. The indolizine 4 shows excellent potency towards the wild-type virus and the double variant, low cytotoxicity, and good aqueous solubility; however, it and the other 6:5 bicyclics are oddly much less active towards the Y181C single variant. 2015 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 219 224 26166629 Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. The naphthyl azines 8c and 8f are particularly notable; they have sub-10 nM potency towards wild-type HIV-1 and viral variants containing the clinically important Y181C and K103N/Y181C mutations, greater activity than efavirenz particularly towards the K103N-bearing variant, normal cytotoxicity, and solubility that is ca. 2015 Bioorganic & medicinal chemistry letters Introduction HIV K103N;K103N;Y181C;Y181C 173;253;163;179 178;258;168;184 26192603 The use of dried blood spot specimens for HIV-1 drug resistance genotyping in young children initiating antiretroviral therapy. Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most commonly detected in DBS and plasma, particularly Y181C/I (28% and 27%) and K103N/S (15% and 13%) respectively (Figure 1). 2015 Journal of virological methods Introduction HIV K103N;K103S;Y181C;Y181I 155;155;129;129 162;162;136;136 NNRTI;NNRTI 0;48 36;53 26192603 The use of dried blood spot specimens for HIV-1 drug resistance genotyping in young children initiating antiretroviral therapy. Only one specimen was predicted to be resistant to protease inhibitors (PI) due to the presence of major and minor PI mutations (L10F, M46I, I54V, L76V and V82A) while 8 specimens had minor PI mutations (A71T (n=3), L10I/V (n=3) and M46L/T (n=2)). 2015 Journal of virological methods Introduction HIV A71T;I54V;L10F;L10I;L10V;L76V;M46I;M46L;M46T;V82A 204;141;129;216;216;147;135;233;233;156 209;145;133;222;222;151;139;239;239;160 PR;PI;PI;PI 51;72;115;190 59;74;117;192 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Although substitutions at positions M50I, H51Y or E138K emerged under DTG pressure after R263K, none of these was able to restore viral replicative capacity to wild-type levels. 2015 Viruses Introduction HIV E138K;H51Y;M50I;R263K 50;42;36;89 55;46;40;94 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. For example, one treatment-naive participant in the dose-ranging SPRING-1 clinical trial who was treated with a suboptimal 10 mg dose of DTG and who failed therapy developed the M184M/V substitution in RT, showing that the ability of 50 mg DTG to prevent the emergence of drug resistance against the NRTIs that are co-administered with it is dose-dependent. 2015 Viruses Introduction HIV M184M;M184V 178;178 185;185 NRTI;RT 300;202 305;204 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Furthermore, there is a high degree of likelihood that DTG will remain active against the latter viruses because of the very long dissociative half-life between DTG and integrase protein, very tight binding between DTG and integrase, and because the level of resistance against DTG that is conferred by the R263K/H51Y substitutions is relatively slight. 2015 Viruses Introduction HIV H51Y;R263K 313;307 317;312 IN;IN 169;223 178;232 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Hence, withdrawal of therapy for reasons that relate to either non-adherence or a treatment interruption would be expected to yield mostly WT viruses and replication-competent drug-resistant viruses but not viruses containing the R263K/H51Y DTG-resistant viruses that have been shown to have vastly diminished replicative capacity and integrase activity. 2015 Viruses Introduction HIV H51Y;R263K 236;230 240;235 IN 335 344 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Importantly, the M184I substitution was transiently detected within the HIV integrated DNA from one individual undergoing RAL intensification, an observation that confirmed that RAL use does not protect against the emergence of viruses that are resistant against NRTIs. 2015 Viruses Introduction HIV M184I 17 22 NRTI 263 268 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. In contrast, very few patients in the DTG arm developed new drug resistance although the viral isolates from two individuals with protocol-defined virological failure (PDVF) after 24 weeks of treatment were found to have developed a R263K integrase substitution or a R263K/R mixture. 2015 Viruses Introduction HIV R263K;R263K;R263R 233;267;267 238;274;274 IN 239 248 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. In particular, the combination of N155H in integrase with M184M/I/V in reverse transcriptase was commonly observed. 2015 Viruses Introduction HIV M184I;M184M;M184V;N155H 58;58;58;34 67;67;67;39 RT;IN 71;43 92;52 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Less frequently, the K65R substitution in RT was found in combination with M184I/V and integrase resistance mutations. 2015 Viruses Introduction HIV K65R;M184I;M184V 21;75;75 25;82;82 IN;RT 87;42 96;44 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184I/V were the most common resistance mutations in this study. 2015 Viruses Introduction HIV M184V;M184I 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Moreover, R263K also inhibited the ability of HIV to develop of resistance against RT inhibitors such as 3TC, an observation that helps to explain the excellent clinical trial results obtained to date with DTG. 2015 Viruses Introduction HIV R263K 10 15 RT 83 85 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Nor did the R263K/R mixture further evolve towards a pure R263K population. 2015 Viruses Introduction HIV R263K;R263K;R263R 12;58;12 19;63;19 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. One of them possessed an integrase V151V/I mixed population that was not phenotypically resistant against DTG while the other possessed substitutions at positions T97A and E138T/A and was shown to have high levels of resistance against DTG. 2015 Viruses Introduction HIV E138A;E138T;T97A;V151I;V151V 172;172;163;35;35 179;179;167;42;42 IN 25 34 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Resistance mutations that were found in viral isolates from treatment-naive participants who experienced treatment failure during the initial dose-ranging Protocol 004 clinical trial were: L74L/M, V151I, N155H, Y143R and S230R in integrase (IN) and M184M/I/V and K65K/R in RT (Table 1). 2015 Viruses Introduction HIV K65K;K65R;L74L;L74M;M184I;M184M;M184V;N155H;S230R;V151I;Y143R 263;263;189;189;249;249;249;204;221;197;211 269;269;195;195;258;258;258;209;226;202;216 IN;IN;RT 230;241;273 239;243;275 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Site-directed mutagenesis confirmed that R263K confers low-level resistance to DTG and work with recombinant integrase enzyme containing R263K showed that this substitution decreases the affinity of the integrase protein for DNA and its ability to perform strand transfer. 2015 Viruses Introduction HIV R263K;R263K 41;137 46;142 IN;IN 109;203 118;212 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. The growth of R263K-containing viruses in tissue culture for more than four years has not yet led to the identification of any additional compensatory substitution that might be able to reverse the consequences of R263K. 2015 Viruses Introduction HIV R263K;R263K 14;214 19;219 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. The presence of the R263K substitution (2/4) amongst viral isolates from individuals who experienced PDVF in this study was in agreement with previous work that had selected R263K in tissue culture with DTG over 20 weeks. 2015 Viruses Introduction HIV R263K;R263K 20;174 25;179 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. The virus from one of the individuals who experienced RAL-based treatment failure was found to possess only the M184V resistance substitution, in the absence of any mutation in the integrase coding sequence, whereas the other viruses were found to be resistant against both integrase and RT inhibitors. 2015 Viruses Introduction HIV M184V 112 117 IN;IN;RT 181;274;288 190;283;290 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. This result might also be explained by the fact that a further decrease in viral replicative capacity occurs when the R263K substitution in integrase and the M184I/V substitutions in RT are combined in the same virus, compared to the presence of either substitution alone. 2015 Viruses Introduction HIV M184I;M184V;R263K 158;158;118 165;165;123 IN;RT 140;183 149;185 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Tissue culture assays with viruses containing R263K revealed that this mutation compromised each of viral infectivity, viral replicative capacity, and integration of viral DNA in both cell lines and in primary human peripheral mononuclear cells (PBMCs). 2015 Viruses Introduction HIV R263K 46 51 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Under such circumstances, extensive genotypic characterisation of resistant strains from two large clinical studies, i.e., Studies 102 and 103, revealed the emergence of the T66I, E92Q, T97A, Q148R and N155H resistance mutations in integrase, mostly in combination with the M184I/V substitutions in RT. 2015 Viruses Introduction HIV E92Q;M184I;M184V;N155H;Q148R;T66I;T97A 180;274;274;202;192;174;186 184;281;281;207;197;178;190 IN;RT 232;299 241;301 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. When the protease inhibitor darunavir (DRV) was used in combination with RAL in the NEAT/ANRS143 clinical trial, only the N155H resistance mutation in integrase was found, in the absence of any mutation in PR. 2015 Viruses Introduction HIV N155H 122 127 IN;PR;PR 151;9;206 160;17;208 26241860 The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon. Group O natural polymorphism also has an impact on treatment options, since most strains naturally present the Y181C mutation in the Reverse Transcriptase (RT) conferring resistance to Efavirenz and Nevirapine (first generation Non Nucleoside RT Inhibitors, NNRTIs). 2015 PLoS pathogens Introduction HIV Y181C 111 116 RT;NNRTI;RT;RT 133;258;156;243 154;264;158;245 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. A K65R mutation in the reverse transcriptase gene of HIV-1, which confers low-level (~2-5 fold) resistance to TFV, has been documented in patients failing TFV-containing regimens and may increase exposure of uninfected persons to TFV-resistant HIV-1K65R viruses. 2015 Retrovirology Introduction HIV K65R 2 6 RT 23 44 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. Furthermore, the K65R mutation is known to have a high fitness cost to viral replication, and thus is often rapidly outgrown by the more fit wild-type virus. 2015 Retrovirology Introduction HIV K65R 17 21 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. Here, we expand the use of the macaque model to evaluate the efficacy of topically delivered TFV from a gel against a TFV-resistant SHIV containing the K65R mutation that recapitulates the resistance and fitness profile of HIV-1 with the K65R mutation. 2015 Retrovirology Introduction HIV K65R;K65R 152;238 156;242 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. The K65R mutation is also observed in persons virologically failing while on stavudine (d4T)-containing therapy, a first-line regimen extensively implemented in early treatment programs in the developing world. 2015 Retrovirology Introduction HIV K65R 4 8 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. The reversion of K65R can be facilitated by insufficient drug pressure through inconsistent product use and low systemic TFV exposures, which could underestimate clinical K65R-related TFV failures. 2015 Retrovirology Introduction HIV K65R;K65R 17;171 21;175 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. This model was further used to evaluate the efficacy of FTC/TDF against drug-resistant SHIV containing either K65R or the emtricitabine-associated M184V mutation. 2015 Retrovirology Introduction HIV K65R;M184V 110;147 114;152 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. At the C terminus, 17/23 patients had amino acid changes versus consensus M including mutations L449P, S451N, and P453L that previously were associated with PI exposure and/or resistance. 2015 AIDS research and human retroviruses Introduction HIV L449P;P453L;S451N 96;114;103 101;119;108 PI 157 159 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. E12K, described as accelerating the emergence of resistance in concert with other Gag mutations, was the most frequent, present in 21/23 patients, and is in fact the consensus amino acid in most non-B subtypes. 2015 AIDS research and human retroviruses Introduction HIV E12K 0 4 Gag 82 85 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. For example, the R76K mutation has previously been described as affecting PI susceptibility but here selection from an R/K mix pre-PI to each of Q and R at failure was observed in different patients, as well as R76K, K76R/K, and K76R in three other patients. 2015 AIDS research and human retroviruses Introduction HIV K76K;K76R;K76R;R76K;R76K 217;217;229;17;211 223;223;233;21;215 PI;PI 74;131 76;133 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. In patient 15, the A431V mutation developed in the NC/p1 cleavage site at failure with major mutation V82A, a coevolution that is frequently observed. 2015 AIDS research and human retroviruses Introduction HIV A431V;V82A 19;102 24;106 NC 51 53 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Mutation P453L was present in 4/11 subtype A patients, but again is not a consensus residue in subtypes A, C, or D. 2015 AIDS research and human retroviruses Introduction HIV P453L 9 14 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Of note, mutations M36I and H69K were present in all subtype A and C patient viruses and I93L was present in all subtype C viruses, and were consensus residues in each subtype, respectively. 2015 AIDS research and human retroviruses Introduction HIV H69K;I93L;M36I 28;89;19 32;93;23 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Of particular interest, two CSMs developed in two separate patients at the time of failure:R361K (in two subtype A patients:1 and 3) and P453L (in subtype A patient 8 and subtype C patient 17). 2015 AIDS research and human retroviruses Introduction HIV P453L;R361K 137;91 142;96 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Of particular relevance to this study were mutations associated with resistance to boosted lopinavir: L10I (three subtype A patients), L10V (one subtype A), K20R (five subtype As and 1 subtype C), L33V (one subtype D), L63P (one subtype A, two subtype Cs, and three subtype Ds). 2015 AIDS research and human retroviruses Introduction HIV K20R;L10I;L10V;L33V;L63P 157;102;135;197;219 161;106;139;201;223 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Other common mutations included L10V (observed in four patients), G16E (four patients), and K20R (six patients), none of which was a consensus residue in subtype A, C, or D. 2015 AIDS research and human retroviruses Introduction HIV G16E;K20R;L10V 66;92;32 70;96;36 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. The cleavage site mutation S451N was found in 7/23 patients (4/7 subtype C, 2/5 subtype D, and 1/11 subtype A), but is not a consensus residue in these subtypes. 2015 AIDS research and human retroviruses Introduction HIV S451N 27 32 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. The development of Y79F at failure was present in two patients, although F79Y was also observed in a third, and T81A was also observed at failure in a single patient. 2015 AIDS research and human retroviruses Introduction HIV F79Y;T81A;Y79F 73;112;19 77;116;23 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. The L449P mutation was present in all patients infected with subtype A (n = 11), in keeping with the finding of another study reporting P as the consensus amino acid at position 449 in subtype A. 2015 AIDS research and human retroviruses Introduction HIV L449P 4 9 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. The major LPV resistance mutation I54V developed at failure in two patients (6 and 8) and V82A in two additional patients (4 and 15). 2015 AIDS research and human retroviruses Introduction HIV I54V;V82A 34;90 38;94 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. The presence of minor resistance mutations in protease in non-B subtypes has been widely reported: 63P is the consensus residue in subtype D, L10I is present in 19% of subtype A sequences, and K20R is present in 22% of subtype A and 15% of subtype Cs. 2015 AIDS research and human retroviruses Introduction HIV K20R;L10I 193;142 197;146 PR 46 54 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. To our knowledge R361K has not been previously linked to PI resistance or exposure, but P453L has been associated with PI exposure in vitro, in vivo, and with PI resistance. 2015 AIDS research and human retroviruses Introduction HIV P453L;R361K 88;17 93;22 PI;PI;PI 57;119;159 59;121;161 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. Two patients developed a new minor resistance mutation at failure (patient 3, K20R and 4, L10I) and two patients had mutations at minor resistance position 63, though to different residues (16 to I and 11 to S). 2015 AIDS research and human retroviruses Introduction HIV K20R;L10I 78;90 82;94 26258548 Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. were also common with R76K in 13/23 patients (6/11 subtype A, 4/7 subtype C, and 3/5 subtype D) and Y79F in 10/23 patients (3/11 subtype A, 4/7 subtype C, and 3/5 subtype D); in fact, 76K is the consensus residue in subtype D viruses. 2015 AIDS research and human retroviruses Introduction HIV R76K;Y79F 22;100 26;104 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Three genotypic resistance pathways were identified: N155H (+-E92Q), Q148H/R/K (+-G140S) and Y143R (+-T97A). 2015 The Journal of antimicrobial chemotherapy Introduction HIV E92Q;G140S;N155H;Q148H;Q148K;Q148R;T97A;Y143R 62;82;53;69;69;69;102;93 66;87;58;78;78;78;106;98 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In this study, we used AS-PCR to analyze expression dynamics of eight drug resistance mutations (M41L, K65R, K70R, K103N, Y181C, M184V and T215F/Y) during the clinical course of ARV-treated individuals with documented virologic failures and drug-resistant HIV-1. 2015 PloS one Introduction HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y;Y181C 115;103;109;129;97;139;139;122 120;107;113;134;101;146;146;127 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Low-frequency K103N was detected by highly-sensitive method for 6 to 12 month after the mutation was no longer detectable by bulk sequencing. 2015 PloS one Introduction HIV K103N 14 19 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Here; we have explored the conformational variation for the PR20 mutant with the inactivating D25N mutation (PR20D25N). 2015 Journal of molecular graphics & modelling Introduction HIV D25N 94 98 PR 60 62 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Introduction of the D25N mutation into wild-type PR in experimental systems increased the equilibrium dimer dissociation constant by more than 100-fold and decreased the binding affinity of DRV by about 106 fold; although no significant alteration was observed in the inhibitor-bound dimer structure. 2015 Journal of molecular graphics & modelling Introduction HIV D25N 20 24 PR 49 51 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Recently; for example; the effects of single mutations V32I and M46L were studied by molecular dynamics in. 2015 Journal of molecular graphics & modelling Introduction HIV M46L;V32I 64;55 68;59 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. The D25N mutation is commonly introduced to prevent autoproteolytic degradation when studying the protease structure. 2015 Journal of molecular graphics & modelling Introduction HIV D25N 4 8 PR 98 106 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. The effect of the D25N mutation was evaluated in the MD simulations for comparison with the experimental studies. 2015 Journal of molecular graphics & modelling Introduction HIV D25N 18 22 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. ASPCR was performed for the most common and frequent key resistance mutations: K70R selected early and transiently by AZT and T215Y/F selected by AZT, K103N and Y181C selected by NVP, and the M184V mutation selected by 3TC. 2015 PloS one Introduction HIV K103N;K70R;M184V;T215F;T215Y;Y181C 151;79;192;126;126;161 156;83;197;133;133;166 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. High level and complex profile of HIV-1 drug resistance mutations including Q151M and thymidine analogue mutations (TAMs) in individuals with first-line ART failure and increased prevalence of transmitted drug resistance (TDR) mutations have been reported in recent years, despite more promising initial observations from Africa. 2015 PloS one Introduction HIV Q151M 76 81 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Finally, we analyzed the role of H221Y in resistance to commonly used drugs in China (Efavirenz EFV, Zidovudine AZT, Lamivudine 3TC, and Stavudine d4T) and the interactions between H221Y and Y181C. 2015 Virology journal Introduction HIV H221Y;H221Y;Y181C 33;181;191 38;186;196 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. H221Y is reported to be strongly associated with drug therapy, but its role is not clear. 2015 Virology journal Introduction HIV H221Y 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Results of HIV-1 drug resistance surveillance in patients who fail first-line antiretroviral therapy showed H221Y usually accompanied the position mutations of T215Y, K103N, Y181 of RT. 2015 Virology journal Introduction HIV H221Y;K103N;T215Y 108;167;160 113;172;165 RT 182 184 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. This hypothesis is based on the rapid loss of the M184V mutation in the absence of selective pressure from taking antiretroviral agents. 2016 Tropical medicine & international health Introduction HIV M184V 50 55 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. We hypothesized that the detection of M184V compared to no detectable M184V would be associated with less immunologic failure and a less steep CD4 count decline during viremia. 2016 Tropical medicine & international health Introduction HIV M184V;M184V 38;70 43;75 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. I54M and L90M single mutations were not found to have a disruptive effect on the secondary or tertiary structure. 2015 Viruses Introduction HIV L90M;I54M 9;0 13;4 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. Of the treatment-associated mutations observed in HIV-2 protease, I54M and L90M have been shown to be implicated in the reduced susceptibility to certain protease inhibitors in phenotypic assays, but as far as we know, their effects have never been characterized in association with all of the inhibitors, neither enzymatically nor in cell culture. 2015 Viruses Introduction HIV I54M;L90M 66;75 70;79 PR;PR 56;154 64;162 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. The effects of I54M and L90M single mutations have already been described based on the amprenavir complexes of HIV-1 PR and its drug resistant mutants, but to the best of our knowledge, there are no structural data available for I54M and/or L90M mutants of HIV-2 PR. 2015 Viruses Introduction HIV I54M;I54M;L90M;L90M 15;229;24;241 19;233;28;245 PR;PR 117;263 119;265 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. In the present study, we have scrutinized the behavior of the minor mutation V77I along with co-occurring mutations L33F and K20T and have considered the two types of mutants, a double mutant, V77I-L33F (DBM) and a triple mutant, V77I-L33F-K20T (TPM); according to their actual prevalence (Table 1). 2015 BMC bioinformatics Introduction HIV K20T;K20T;L33F;L33F;L33F;V77I;V77I;V77I 125;240;116;198;235;77;193;230 129;244;120;202;239;81;197;234 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. K20T is the most prominent mutation occurring at the 20th residue and has been found to co-occur with V77I in subtype B population. 2015 BMC bioinformatics Introduction HIV V77I;K20T 102;0 106;4 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. L23I, D30N, E35G, M46I/L/V, G48V, I54L, G73S/T/C/A, T74S, V82A/F/S/T, I84V, N88D/S and L90M are other mutations correlated to NFV resistance. 2015 BMC bioinformatics Introduction HIV D30N;E35G;G48V;G73A;G73C;G73S;G73T;I54L;I84V;L90M;M46I;M46L;M46V;N88D;N88S;T74S;V82A;V82F;V82S;V82T;L23I 6;12;28;40;40;40;40;34;70;87;18;18;18;76;76;52;58;58;58;58;0 10;16;32;50;50;50;50;38;74;91;26;26;26;82;82;56;68;68;68;68;4 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. L33F co-occurs with V77I in large number of HIV-1 subtype B infected patient samples, as reported in Stanford's HIV Drug Resistance Database. 2015 BMC bioinformatics Introduction HIV V77I;L33F 20;0 24;4 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. L33F is a major mutation present in the active site of the protease, which results in reduced susceptibility towards NFV in the presence of other mutations. 2015 BMC bioinformatics Introduction HIV L33F 0 4 PR 59 67 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. L33I is a less commonly occurring mutation with similar effects to L33F, while L33V mutation has not been related to any kind of drug resistance in PI therapy. 2015 BMC bioinformatics Introduction HIV L33F;L33V;L33I 67;79;0 71;83;4 PI 148 150 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. The other mutations which were co-occurring with DBM and TPM included major mutations like- M46IL, I54MV, I84V, L90M, N88S, V32I, I47V, V82AS, D30N, G48V; and accompanied by minor mutations like- L10I, I13V, L63P, A71V, L89M, I93L, E35DN, I15V, D60E, L24I etc. 2015 BMC bioinformatics Introduction HIV A71V;D30N;D60E;E35D;E35N;G48V;I13V;I15V;I47V;I54M;I54V;I84V;I93L;L10I;L24I;L63P;L89M;L90M;M46I;M46L;N88S;V32I;V82A;V82S 214;143;245;232;232;149;202;239;130;99;99;106;226;196;251;208;220;112;92;92;118;124;136;136 218;147;249;237;237;153;206;243;134;104;104;110;230;200;255;212;224;116;97;97;122;128;141;141 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. V77I is one of the important non active site secondary mutations in HIV-PR, causing resistance against Nelfinavir (NFV). 2015 BMC bioinformatics Introduction HIV V77I 0 4 PR 72 74 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Also, the SIV Gag K165R escape mutation was archived in latent proviral DNA and was present in resting CD4+ T cells, indicating that the replication competent SIV bearing the escape mutation persisted in latent reservoirs such as the brain. 2016 Journal of neurovirology Introduction HIV K165R 18 23 Gag 14 17 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Correspondingly, longitudinal CSF and plasma SIV RNA sequencing revealed the development of a canonical escape in SIV Gag KP9 (K165R) following the emergence of Mane-A1*084:01/Gag KP9 tetramer-specific CTLs, demonstrating that CTL-mediated immunologic pressure was driving the escape. 2016 Journal of neurovirology Introduction HIV K165R 127 132 Gag;Gag 118;176 121;179 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. In the case of SIV Gag K165R escape, pronounced loss of fitness was demonstrated by rapid reversion to wildtype in animals that did not respond to KP9 (Mane-A1*084:01-negative animals); however, the development of rapid and significant development of the compensatory mutation V145A reduced the fitness defect of K165R. 2016 Journal of neurovirology Introduction HIV K165R;K165R;V145A 23;313;277 28;318;282 Gag 19 22 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. In this study, we engineered the gag K165R point mutation into the neurovirulent molecular clone SIV/17E-Fr. 2016 Journal of neurovirology Introduction HIV K165R 37 42 Gag 33 36 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Reversion to wildtype SIV Gag KP9 in animals inoculated with SIV/17E-Fr K165R also only occurred in the CSF. 2016 Journal of neurovirology Introduction HIV K165R 72 77 Gag 26 29 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. The main goal of this study was to evaluate the potential fitness cost of SIV Gag K165R, an escape mutation that develops as the result of CTL-mediated immune pressure associated with the known neuroprotective MHC class I allele Mane-A1*084:01. 2016 Journal of neurovirology Introduction HIV K165R 82 87 Gag 78 81 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. We show that inoculation of Mane-A1*084:01-positive pigtailed macaques with SIV/17E-Fr K165R resulted in lowered CSF viral loads compared to macaques inoculated with wildtype SIV/17E-Fr. 2016 Journal of neurovirology Introduction HIV K165R 87 92 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. Among 121 seroconverters from the Partners PrEP Study, a randomized, placebo-controlled trial of FTC/TDF and TDF as PrEP, we previously reported detection of PrEP-related mutations (K65R, K70E and/or M184IV) by ultra-deep sequencing in 9 individuals at the time HIV seroconversion was first detected. 2016 AIDS (London, England) Introduction HIV K65R;K70E;M184I;M184V 182;188;200;200 186;192;206;206 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. Another remarkable finding of our study was that, in addition to identifying K65R, additional resistance mutations detected with MiSeq relative to Sanger mainly affected the predicted susceptibility to the second-generation NNRTIs ETR and RPV, but did not largely influence viral susceptibility to other ARVs, including AZT. 2016 AIDS (London, England) Introduction HIV K65R 77 81 NNRTI 225 231 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. Considering Sanger and deep sequencing results together and assuming that none of the 5 subjects not evaluable by MiSeq had the K65R mutation, a conservative estimate of the overall prevalence of K65R mutation was 69.6%, a 10.1% increase in prevalence relative to Sanger sequencing. 2016 AIDS (London, England) Introduction HIV K65R;K65R 129;197 133;201 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. However, its efficacy is diminished in the presence of the K65R mutation. 2016 AIDS (London, England) Introduction HIV K65R 59 63 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. K65R mutation was found in 8 of the 27 samples evaluable by MiSeq (29.6%) at frequencies in the virus population ranging 1.3% to 32.5%. 2016 AIDS (London, England) Introduction HIV K65R 0 4 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. Plasma samples from those with no K65R mutation by Sanger sequencing were reanalysed at the irsiCaixa AIDS Research Institute in Badalona, Spain using MiSeq Illumina (Illumina Inc. 2016 AIDS (London, England) Introduction HIV K65R 34 38 AIDS 102 106 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. Sanger sequencing detected K65R mutation in 47 out of 79 samples (59.5%). 2016 AIDS (London, England) Introduction HIV K65R 27 31 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. The fitness cost of the K65R mutation, however, makes K65R mutants wane and thus might be missed by Sanger methods. 2016 AIDS (London, England) Introduction HIV K65R;K65R 24;54 28;58 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. To date, rates of virological failure to first-line TDF regimens and transmission of K65R mutants have remained low according to Sanger sequencing estimates. 2016 AIDS (London, England) Introduction HIV K65R 85 89 26807968 Treatment options after virological failure of first-line tenofovir-based regimens in South Africa: an analysis by deep sequencing. Using Sanger sequencing, previous studies reported the emergence of K65R mutation in 23 to 69.7% of participants developing virological failure to 1st-line TDF regimens. 2016 AIDS (London, England) Introduction HIV K65R 68 72 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. In individuals receiving tenofovir, HIV-1 develops phenotypically and clinically significant resistance usually as a result of one mutation at position 65 (lysine to arginine; K65R) in the reverse transcriptase (RT) gene. 2016 The Lancet. Infectious diseases Introduction HIV K65R;K65R 176;152 180;177 RT;RT 189;212 210;214 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Among these, Q151M is the most important mutation. 2016 Nucleic acids research Introduction HIV Q151M 13 18 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Amongst the 45 amino acid exchanges in the MR-RT compared to the CRF02_AG WT RT, TAMs for the excision pathway as well as discrimination mutations from the Q151M MDR complex, and in addition K65R are present. 2016 Nucleic acids research Introduction HIV K65R;Q151M 191;156 195;161 RT;RT 46;77 48;79 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Excision of the incorporated inhibitor is due to five primary resistance substitutions (M41L, D67N, K70R, T215F/Y and K219Q/E) also called TAMs because they emerge upon treatment with the thymidine analogs AZT and stavudine (d4T). 2016 Nucleic acids research Introduction HIV D67N;K219E;K219Q;K70R;M41L;T215F;T215Y 94;118;118;100;88;106;106 98;125;125;104;92;113;113 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Furthermore, treatment with d4T appears to be directly associated with Q151M and in addition K65R. 2016 Nucleic acids research Introduction HIV K65R;Q151M 93;71 97;76 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. However, transient kinetic analyses showed that the combination of TAMs and K65R also decreases the ability of the RT to discriminate against NRTIs. 2016 Nucleic acids research Introduction HIV K65R 76 80 NRTI;RT 142;115 147;117 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In HIV-1 subtype B a sixth TAM, L210W, often occurs together with M41L and T215Y and contributes substantially to high-level AZT resistance. 2016 Nucleic acids research Introduction HIV L210W;M41L;T215Y 32;66;75 37;70;80 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In HIV-2, AZT discrimination is characterized by the mutations A62V, V75I, F77I, F116Y and Q151M. 2016 Nucleic acids research Introduction HIV A62V;F116Y;F77I;Q151M;V75I 63;81;75;91;69 67;86;79;96;73 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Moreover, MR-RT harbors the G190E mutation conferring resistance against NNRTIs, whereas several of the other exchanges have been identified as compensatory mutations in subtype B RT which help to improve the replication capacity of the virus. 2016 Nucleic acids research Introduction HIV G190E 28 33 NNRTI;RT;RT 73;13;180 79;15;182 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Q151M alone or the Q151M MDR complex also emerge in HIV-1 upon treatment with inhibitors that are poor substrates for the excision reaction, since Q151M confers multi-NRTI resistance to most NRTIs and nucleotide RT inhibitors (NtRTIs), except tenofovir disoproxil fumarate (TDF). 2016 Nucleic acids research Introduction HIV Q151M;Q151M;Q151M 19;147;0 24;152;5 NRTI;NRTI;RT 167;191;212 171;196;214 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Q151M has been detected in HIV-1 upon combination chemotherapy with AZT plus didanosine (ddI) or ddC. 2016 Nucleic acids research Introduction HIV Q151M 0 5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Q151M is usually the first mutation to appear followed by at least two additional amino acid exchanges of the Q151M MDR complex. 2016 Nucleic acids research Introduction HIV Q151M;Q151M 110;0 115;5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Similar to HIV-2, Q151M in HIV-1 appears to impede the incorporation of AZTTP rather than enhancing the excision of incorporated AZTMP. 2016 Nucleic acids research Introduction HIV Q151M 18 23 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Structural analyses of a K65R RT indicate that the guanidinium planes of K65R and the conserved residue R72 are stacked, thereby forming a molecular platform which restricts rotation of both residues. 2016 Nucleic acids research Introduction HIV K65R;K65R 25;73 29;77 RT 30 32 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The major TAM T215Y results in pi-pi stacking of the aromatic rings of ATP and Tyr and it is thus essential for AZTMP excision. 2016 Nucleic acids research Introduction HIV T215Y 14 19 PI;PI 31;34 33;36 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Thus the mutation pattern is also called Q151M multi-drug resistance (MDR) complex. 2016 Nucleic acids research Introduction HIV Q151M 41 46 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Thus, in the context of TAMs, K65R leads to a counteraction of excision and discrimination, resulting in AZT susceptibility. 2016 Nucleic acids research Introduction HIV K65R 30 34 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. While Q151M and K65R are positively associated to each other, the occurrence of K65R antagonizes nucleotide excision caused by TAMs since it interferes with ATP binding, necessary for NRTI excision. 2016 Nucleic acids research Introduction HIV K65R;K65R;Q151M 16;80;6 20;84;11 NRTI 184 188 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. The latest International AIDS Society (IAS)-USA panel list shows 11 mutations associated with DRV resistance: V11I, V32I, L33F, I47V, I50V, I54M/L, T74P, L76V, I84V, and L89V (Wensing et al.,). 2016 Frontiers in microbiology Introduction HIV I47V;I50V;I54L;I54M;I84V;L33F;L76V;L89V;T74P;V11I;V32I 128;134;140;140;160;122;154;170;148;110;116 132;138;146;146;164;126;158;174;152;114;120 AIDS 25 29 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. We obtained a variant with high-level resistance to DRV, which carries I47V and I50V in the PR region. 2016 Frontiers in microbiology Introduction HIV I47V;I50V 71;80 75;84 PR 92 94 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Furthermore, the presence of Y135F in the infecting HIV-1 strain may signal the presence of other unknown A*24:02-associated escape mutations in other viral epitopes that might also compromise CTL responses to the incoming HIV strain. 2016 PloS one Introduction HIV Y135F 29 34 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. If this were the case, infection of A*24:02-expressing persons (representing the majority of Japanese individuals) by Y135F-containing HIV-1 (representing the majority of Japanese HIV strains) could bring about graver prognosis than infection by Y135-containing virus. 2016 PloS one Introduction HIV Y135F 118 123 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. In theory, CTL responses to these epitopes in A*24:02-expressing persons may differ depending on whether the individual is infected with HIV-1 harboring wild-type (Y135) versus escaped (Y135F) form at this residue: in particular, initial CTL responses to these epitopes in the latter case might be reduced or absent. 2016 PloS one Introduction HIV Y135F 186 191 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Indeed, one of the most well-characterized HLA class I-associated escape mutations in HIV, a tyrosine to phenylalanine mutation at Nef codon 135 (Y135F) that is reproducibly selected in A*24:02-expressing individuals represents the population consensus sequence in Japan, whereas the global HIV subtype B consensus is the wild-type tyrosine (Y135) (http://www.hiv.lanl.gov/). 2016 PloS one Introduction HIV Y135F 146 151 Nef 131 134 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Our analysis suggested more rapid CD4 decline in A*24:02-expressing individuals inferred to have been infected with Y135F-containing HIV-1. 2016 PloS one Introduction HIV Y135F 116 121 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. To investigate this, we identified A*24:02-expressing individuals likely to have been infected with escaped (Y135F) versus wild-type (Y135) HIV-1, from within our well-characterized chronic HIV-1 infection cohort, and compared these two groups with respect to their longitudinal HIV-1 clinical outcomes. 2016 PloS one Introduction HIV Y135F 109 114 HIV infections 182 205 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Comparing the wild type with these hyperstable mutants provides insight into the stabilizing effect of disulfide bonds (A204C and A14C/E45C) compared with hydrophobic interactions (E45A and E45A/R132T). 2016 Retrovirology Introduction HIV A14C;A204C;E45A;E45A;E45C;R132T 130;120;181;190;135;195 134;125;186;194;139;200 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Finally, we measured the stiffness of wild-type and E45A viral cores (i.e., of filled capsids) purified from virus particles. 2016 Retrovirology Introduction HIV E45A 52 56 Capsid 86 93 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. A baseline genotypic resistance test revealed the nucleoside reverse transcriptase inhibitor-resistance mutations L210W and T215D that were interpreted as causing intermediate resistance to zidovudine and low-level resistance to tenofovir; the non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistance mutations K101P and K103S that were interpreted as causing high-level resistance to each of the NNRTIs; and the protease inhibitor-resistance mutations D30N, L33F, I54V, N88D, and L90M that were interpreted as causing intermediate or high-level resistance to each of the PIs except darunavir. 2016 AIDS research and human retroviruses Introduction HIV D30N;I54V;K101P;K103S;L210W;L33F;L90M;N88D;T215D 462;474;320;330;114;468;490;480;124 466;478;325;335;119;472;494;484;129 NNRTI;NRTI;PR;NNRTI;NNRTI;PI 244;50;422;292;406;581 280;82;430;297;412;584 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Although the patient's genotypic resistance test was reported as being associated with intermediate resistance to raltegravir and elvitegravir based on the presence of G140S, no change to therapy was made because of the patient's virological and immunological response to therapy. 2016 AIDS research and human retroviruses Introduction HIV G140S 168 173 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Among the site-directed mutants, Q148N had a higher replication capacity than Q148H (88% vs. 2016 AIDS research and human retroviruses Introduction HIV Q148H;Q148N 78;33 83;38 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. In 2015, we created a panel of infectious molecular clones to assess the effect of the novel mutation Q148N on INSTI susceptibility. 2016 AIDS research and human retroviruses Introduction HIV Q148N 102 107 INSTI 111 116 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. It also contained a recombinant infectious molecular clone from the patient's August 2014 sample and clones in which G140S alone and G140S and Q148N were independently mutated back to the wild type residues at these positions. 2016 AIDS research and human retroviruses Introduction HIV G140S;G140S;Q148N 117;133;143 122;138;148 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Q148N +- G140S was associated with 2.4- to 4.5-fold reduced susceptibility to elvitegravir but not to raltegravir or dolutegravir (Table 1). 2016 AIDS research and human retroviruses Introduction HIV G140S;Q148N 9;0 14;5 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. The panel included site-directed HIV-1 mutants containing G140S+Q148N, Q148N alone, G140S+Q148H, and Q148H alone. 2016 AIDS research and human retroviruses Introduction HIV G140S;G140S;Q148H;Q148H;Q148N;Q148N 58;84;90;101;64;71 63;89;95;106;69;76 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. The test revealed G140S, a nonpolymorphic accessory INSTI-resistance mutation, and Q148N, a previously uncharacterized mutation in the INSTI-binding pocket of integrase enzyme. 2016 AIDS research and human retroviruses Introduction HIV G140S;Q148N 18;83 23;88 IN;INSTI;INSTI 159;52;135 168;57;140 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. This level of INSTI resistance was lower than that observed with Q148H alone (19-fold reduced raltegravir susceptibility and 5.5-fold reduced elvitegravir susceptibility) or Q148H+G140S (>150-fold reduced susceptibility to raltegravir and elvitegravir and 3.4-fold reduced dolutegravir susceptibility). 2016 AIDS research and human retroviruses Introduction HIV G140S;Q148H;Q148H 180;65;174 185;70;179 INSTI 14 19 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. Fifteen of the participants had mutations only to NNRTI (K103N, Y181C, G190A), and three had mutations to NNRTI plus lamivudine (M184V). 2016 AIDS (London, England) Introduction HIV G190A;K103N;M184V;Y181C 71;57;129;64 76;62;134;69 NNRTI;NNRTI 50;106 55;111 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. Fifty-eight had mutations to NNRTI, two had only lamivudine mutations, and two had only tenofovir (K65R) mutations. 2016 AIDS (London, England) Introduction HIV K65R 99 103 NNRTI 29 34 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. Finally, although OLA for K65 was not performed among all 386 participants in 2006, pyrosequencing performed on the 54 participants with subsequent virologic failure found no K65R in this cohort. 2016 AIDS (London, England) Introduction HIV K65R 175 179 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. K65R was evaluated by OLA in 2014 and pyrosequencing was performed on enrollment plasma from those with subsequent virologic treatment failure in 2006. 2016 AIDS (London, England) Introduction HIV K65R 0 4 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. OLA examined point mutations at K103N, Y181C, G190A, and M184V across all specimens. 2016 AIDS (London, England) Introduction HIV G190A;K103N;M184V;Y181C 46;32;57;39 51;37;62;44 27058353 Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya. The study only surveyed drug resistant mutations at codons K103N, Y181C, G190A, M184V, and K65R, which has the potential to underestimate, not overestimate the prevalence of PDR. 2016 AIDS (London, England) Introduction HIV G190A;K103N;K65R;M184V;Y181C 73;59;91;80;66 78;64;95;85;71 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Guided by the prior SAR results, we designed and synthesized three new series (6, 13, and 14) of DAAN derivatives and evaluated them against HIV-1 wild-type virus and the E138K variant, which contains the most frequent mutation conferring resistance to 1b, as well as other resistant viral strains. 2016 Journal of medicinal chemistry Introduction HIV E138K 171 176 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. On the other hand, lead 3b had high antiresistance potency, with especially low resistance fold changes (FC = 1.1-2.1) for K101E and E138K viral strains resistant to new drugs 1a and 1b, respectively, compared with that for wild-type NL4-3 virus. 2016 Journal of medicinal chemistry Introduction HIV E138K;K101E 133;123 138;128 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. In this study, we established a multiplex assay for detecting the drug resistance mutations at 8 loci (M41L, K65R, K101E/Q/P, K103N/S, M184V, G190A, L210W and T215F/Y), which are associated with resistance to commonly used nucleoside reverse transcriptase inhibitors (NRTIs) and Non-nucleoside reverse transcriptase inhibitors (NNRTIs) based on the automated MassARRAY system (Sequenom). 2016 PloS one Introduction HIV G190A;K101E;K101P;K101Q;K103N;K103S;K65R;L210W;M184V;M41L;T215F;T215Y 142;115;115;115;126;126;109;149;135;103;159;159 147;124;124;124;133;133;113;154;140;107;166;166 NNRTI;NRTI;NNRTI;NRTI 279;223;328;268 315;255;334;273 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Capsid Mutations Q63/Q67A and T54A/N57A show delayed uncoating and are defective in nuclear import and integration. 2016 Retrovirology Introduction HIV Q67A;N57A;T54A 21;35;30 25;39;34 Capsid 0 6 27107820 HIV-1 capsid is involved in post-nuclear entry steps. For example, certain mutations in the capsid protein (E45A, R132A, Q219A), which perturb core stability, impair reverse transcription. 2016 Retrovirology Introduction HIV E45A;Q219A;R132A 54;67;60 58;72;65 RT;Capsid 112;38 133;44 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. According to the ECHO and THRIVE studies, E138K was the most frequently selected mutation (45%) detected in ARVnaive patients who have failed RPV therapy which is also often seen with M184I (34%), confering resistance to both lamivudine (3TC) and emtricitabine (FTC). 2016 PloS one Introduction HIV E138K;M184I 42;184 47;189 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. A partial list of NNRTI resistance mutations include: L100I, K103N, V106A, E138K, Y181C, Y188L, and H221Y; these mutations can occur singly, or in combinations. 2016 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K;H221Y;K103N;L100I;V106A;Y181C;Y188L 75;100;61;54;68;82;89 80;105;66;59;73;87;94 NNRTI 18 23 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. DOR loses potency against a number of NNRTI-resistant mutants; however, DOR is generally effective against mutants that reduce the potency of RPV, although DOR did lose some potency against E138K. 2016 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K 190 195 NNRTI 38 43 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. However, in clinical trials individuals on an ETR containing regimen who experienced virological failure were infected with viruses that had a combination of RT mutations including V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, and G190A/S. 2016 Journal of acquired immune deficiency syndromes (1999) Introduction HIV A98G;G190A;G190S;K101E;K101P;L100I;V106I;V179D;V179F;V90I;Y181C;Y181I;Y181V 187;240;240;200;200;193;209;216;216;181;225;225;225 191;247;247;207;207;198;214;223;223;185;234;234;234 RT 158 160 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. In addition, viruses that grew out in an in vitro selection with RPV or a compound closely related to RPV had the RT mutations K101E or E40K, D67E, V111A, E138K, Y181C, and M230I, respectively. 2016 Journal of acquired immune deficiency syndromes (1999) Introduction HIV D67E;E138K;E40K;K101E;M230I;V111A;Y181C 142;155;136;127;173;148;162 146;160;140;132;178;153;167 RT 114 116 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. In clinical trials that involved RPV and two NRTIs, the RT resistance mutations E138K and M184I/V were selected. 2016 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K;M184I;M184V 80;90;90 85;97;97 NRTI;RT 45;56 50;58 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Each of K65R, L74V and M184I/V are major NRTI-related mutations. 2016 Retrovirology Introduction HIV K65R;L74V;M184I;M184V 8;14;23;23 12;18;30;30 NRTI 41 45 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. However, none of the latter could compensate for the loss in replicative capacity conferred by R263K and, in fact, had the effect of further decreasing viral replication, integrase strand-transfer activity and levels of integrated DNA, even though the addition of H51Y to R263K increased resistance to DTG to about sevenfold, as measured by the PhenoSense Integrase Replication Assay (7-10). 2016 Retrovirology Introduction HIV H51Y;R263K;R263K 264;95;272 268;100;277 IN;IN 171;357 180;366 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. However, the combined effects of DTG- and RT-resistance mutations have not been well studied until now, although it is known that the combination of M184I/V and R263K in the same virus further decreased viral replication compared to either mutation alone and no DTG or lamivudine cross-class resistance was observed. 2016 Retrovirology Introduction HIV M184I;M184V;R263K 149;149;161 156;156;166 RT 42 44 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In addition, the emergence of R263K as a secondary substitution has been documented in tissue culture under EVG selection pressure as well as in a Phase two clinical trial of the antiviral activity of EVG. 2016 Retrovirology Introduction HIV R263K 30 35 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In second-line treatment of INSTI-naive patients, a R263K mutation commonly emerged but this substitution causes only about a twofold change in IC50, suggesting that the impact on DTG susceptibility is very low. 2016 Retrovirology Introduction HIV R263K 52 57 INSTI 28 33 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In the phase 3 102 and 103 clinical studies of a once daily pill of EVG/cobicistat/FTC/TFV, the K65R and M184I/V substitutions were detected, separately or in combination, before the emergence of IN mutations in some patients undergoing treatment failure. 2016 Retrovirology Introduction HIV K65R;M184I;M184V 96;105;105 100;112;112 IN 196 198 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. K65R, L74V, K103N, E138K, and M184I/V. 2016 Retrovirology Introduction HIV E138K;K103N;L74V;M184I;M184V;K65R 19;12;6;30;30;0 24;17;10;37;37;4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. L74V has been selected by didanosine and ABC and can confer high-level resistance against these drugs. 2016 Retrovirology Introduction HIV L74V 0 4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. More recently, we have shown that the T66I/R263K combination severely impaired both integrase strand-transfer activity and viral replicative capacity. 2016 Retrovirology Introduction HIV R263K;T66I 43;38 48;42 IN 84 93 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Now, we have studied the effect of R263K or H51Y-R263K in the presence of other clinically relevant RT mutations. 2016 Retrovirology Introduction HIV H51Y;R263K;R263K 44;35;49 48;40;54 RT 100 102 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Of the above, K103N is a major mutation associated with resistance to efavirenz and etravirine; both NNRTIs are known to reduce plasma levels of DTG, thereby limiting their use in co-administration with DTG. 2016 Retrovirology Introduction HIV K103N 14 19 NNRTI 101 107 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Similar impacts on viral replicative capacity and DTG resistance in tissue culture and biochemical assays were observed when the E138K or M50I substitutions were introduced into R263K viruses. 2016 Retrovirology Introduction HIV E138K;M50I;R263K 129;138;178 134;142;183 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Tenofovir, ABC, lamivudine and didanosine can select for K65R, while lamivudine and emtricitabine select for M184I/V. 2016 Retrovirology Introduction HIV K65R;M184I;M184V 57;109;109 61;116;116 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The absence of clinical impact of the R263K mutation has meant that patients harbouring this substitution might be able to remain on DTG therapy. 2016 Retrovirology Introduction HIV R263K 38 43 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The absence of compensatory secondary mutations for R263K is also consistent with the observation that many major RAL- and EVG-resistance substitutions such as G140S, Q148R, E92Q, N155H and Y143R are incompatible with the simultaneous presence of R263K in terms of both integrase strand-transfer activity and viral replication capacity. 2016 Retrovirology Introduction HIV E92Q;G140S;N155H;Q148R;R263K;R263K;Y143R 174;160;180;167;52;247;190 178;165;185;172;57;252;195 IN 270 279 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The E138K substitution in RT has been selected in patients treated with rilpivirine and efavirenz and has resulted in cross-resistance to NNRTIs. 2016 Retrovirology Introduction HIV E138K 4 9 NNRTI;RT 138;26 144;28 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The H51Y/R263K and M50I/R263K viruses may confer similar levels of DTG resistance (about sevenfold resistance against DTG as measured in TZM-bl cells by luciferase assay) while the level of resistance is only about 4.3-fold for the E138K/R263K virus. 2016 Retrovirology Introduction HIV E138K;H51Y;M50I;R263K;R263K;R263K 232;4;19;9;24;238 237;8;23;14;29;243 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The R263K substitution was also selected in vitro, and this was followed by the appearance of such secondary substitutions as H51Y, M50I, and E138K. 2016 Retrovirology Introduction HIV E138K;H51Y;M50I;R263K 142;126;132;4 147;130;136;9 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The T66I/R263K virus was slightly more susceptible to DTG when viruses containing R263K alone were studied but highly resistant to EVG, which explains the emergence of this combination with EVG but not DTG. 2016 Retrovirology Introduction HIV R263K;R263K;T66I 9;82;4 14;87;8 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. We previously showed that R263K-containing viruses possess modestly reduced viral replication capacity (about 70 % compared to WT). 2016 Retrovirology Introduction HIV R263K 26 31 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Few studies on acquired resistance, prior to TDF incorporation in first-line regimens, report first-line resistance in 13 to 94%, with low (13%) K65R levels. 2016 Journal of the International AIDS Society Introduction HIV K65R 145 149 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. The TDF signature reverse transcriptase (RT) resistance mutation K65R, which decreases susceptibility to all nucleoside RT inhibitors (NRTIs) except AZT, has been found to vary by subtype and geographical region upon failure of a TDF-containing first-line regimen: 0 to 6% in subtype A (Europe), 0 to 17% in subtype B (USA and Europe), 12 to 70% in subtype C (South Africa), and 57 to 59% in subtype G and circulating recombinant form (CRF) 02_AG (Nigeria). 2016 Journal of the International AIDS Society Introduction HIV K65R 65 69 RT;NRTI;RT;RT 18;135;41;120 39;140;43;122 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. Among all these mutations, D30N is associated with resistance to nelfinavir (NFV). 2016 International journal of molecular sciences Introduction HIV D30N 27 31 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. D30N also alters the inhibitor binding in the PR-DRV complex. 2016 International journal of molecular sciences Introduction HIV D30N 0 4 PR 46 48 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. In this work, we are interested in the drug resistance mechanics about D30N, I50V, I54M, and V82A mutations. 2016 International journal of molecular sciences Introduction HIV D30N;I50V;I54M;V82A 71;77;83;93 75;81;87;97 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The mutation V82A can decrease the binding affinity. 2016 International journal of molecular sciences Introduction HIV V82A 13 17 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. To obtain information about the binding of GRL-0519 to WT and mutations, MD simulations have been successfully carried out to study the binding mechanics of GRL-0519 and WT and the molecular mechanism of drug resistance reduced by mutations D30N, I50V, I54M, and V82A. 2016 International journal of molecular sciences Introduction HIV D30N;I50V;I54M;V82A 241;247;253;263 245;251;257;267 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Similarly, CA mutant A105T is not restricted by CPSF6-358. 2016 Journal of virology Introduction HIV A105T 21 26 Capsid 11 13 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Some HIV-1 mutants carrying changes in CA, including N74D or P90A, have been shown to induce IFN-beta secretion in MDMs or dendritic cells as a result of cyclic GMP-AMP synthase (cGAS)-mediated recognition of reverse transcription intermediates, indicating that the capsid shell may ordinarily shield viral DNA from recognition by innate immune sensors. 2016 Journal of virology Introduction HIV N74D;P90A 53;61 57;65 RT;Capsid;Capsid 209;266;39 230;272;41 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. The cyclophilin-binding loop CA mutant P90A binds with reduced affinity to peptidylprolyl cis-trans isomerase A, also known as cyclophilin A (CypA), and is resistant to CypA-mediated isomerization of the G89-P90 peptide bond in CA. 2016 Journal of virology Introduction HIV P90A 39 43 Capsid;Capsid 29;228 31;230 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. The HIV-1 CA mutant N74D escapes inhibition by a truncated version of cleavage and polyadenylation specific factor 6 (CPSF6-358) and does not bind a CPSF6-derived peptide in vitro. 2016 Journal of virology Introduction HIV N74D 20 24 Capsid 10 12 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. While HIV-1 CA mutants can escape inhibition by ectopically expressed MX2, we now demonstrate that the infectivities of the HIV-1 CA mutants N74D, A105T, and P90A are hypersensitive to IFN-alpha-induced suppression compared to wild-type virus. 2016 Journal of virology Introduction HIV A105T;N74D;P90A 147;141;158 152;145;162 Capsid;Capsid 12;130 14;132 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Critically, this cytoplasmic trafficking of Nup358 and its association with viral cores is perturbed by mutations which disrupt the hydrophobic binding pocket in assembled CA (N74D) and mutations which disrupt the conserved Cyp binding loop on CA (P90A). 2016 PLoS pathogens Introduction HIV N74D;P90A 176;248 180;252 Capsid;Capsid 172;244 174;246 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. The functional relevance of this interaction was demonstrated by the observation that KIF5B depletion inhibits nuclear import of the viral genome in a CA dependent manner, as N74D and P90A CA mutants are not sensitive to KIF5B depletion. 2016 PLoS pathogens Introduction HIV N74D;P90A 175;184 179;188 Capsid;Capsid 151;189 153;191 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. However, the N155H and SH mutants, which emerge in patients treated with RAL, confer cross-resistance to EVG. 2016 Nucleic acids research Introduction HIV N155H 13 18 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. In a previous study, we compared EVG to RAL and showed that EVG retains potency against the RAL-specific mutant Y143R. 2016 Nucleic acids research Introduction HIV Y143R 112 117 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. The crystal structures also suggested that the N155H and SH mutations indirectly impact the binding of INSTIs in the intasome by altering the conformation of the IN active site. 2016 Nucleic acids research Introduction HIV N155H 47 52 INSTI;IN 103;162 109;164 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Using recombinant enzymes and oligonucleotides mimicking the ends of the retroviral DNA, IN mutants have been extensively characterized and RAL resistance can be recapitulated with three primary mutants: Y143R, N155H and G140S-Q148H (SH). 2016 Nucleic acids research Introduction HIV G140S;N155H;Q148H;Y143R 221;211;227;204 226;216;232;209 IN 89 91 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. While DTG effectively inhibits the Y143R and N155H mutants, the SH double mutant still reduces DTG potency by about 5- to 6-fold. 2016 Nucleic acids research Introduction HIV N155H;Y143R 45;35 50;40 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. All of the compounds experienced some potency loss against the mutants, although they all maintained some activity against the K103N mutant. 2016 Bioorganic & medicinal chemistry letters Introduction HIV K103N 127 132 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. Both drugs selected for mutations on RT, as the V108I mutant emerged after 69 weeks of treatment with 8 and E138K arose after 39 weeks of treatment with 9 (Supp. 2016 Bioorganic & medicinal chemistry letters Introduction HIV E138K;V108I 108;48 113;53 RT 37 39 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. Compounds 8 and 9 also demonstrated some activity against the Y181C and E138K mutants. 2016 Bioorganic & medicinal chemistry letters Introduction HIV E138K;Y181C 72;62 77;67 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. However, none of the compounds inhibited the V108I mutant selected by 8, indicating that there may be conserved binding features among all three molecules that are disrupted by this mutation. 2016 Bioorganic & medicinal chemistry letters Introduction HIV V108I 45 50 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. It did demonstrate some potency against the Y181C RT mutant in the cell-free assay (IC50 = 6.69 muM, data not shown), but was inactive against the K103N, V108I, and E138 K forms of the enzyme. 2016 Bioorganic & medicinal chemistry letters Introduction HIV E138K;K103N;V108I;Y181C 165;147;154;44 171;152;159;49 RT 50 52 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. The three most active compounds against wild type RT were tested against two clinically prominent NNRTI-resistant mutants, K103N and Y181C, as well as the two mutants selected by compounds 8 and 9, V108I and E38K. 2016 Bioorganic & medicinal chemistry letters Introduction HIV E38K;K103N;V108I;Y181C 208;123;198;133 212;128;203;138 NNRTI;RT 98;50 103;52 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. The V108I mutant is associated with resistance to first generation NNRTI (nevirapine (NVP) and efavirenz (EFV)), while the E138K mutant emerges with second generation of drugs (etravirine and rilpivirine), suggesting that the structural differences between 8 and 9 result in different binding characteristics. 2016 Bioorganic & medicinal chemistry letters Introduction HIV E138K;V108I 123;4 128;9 NNRTI 67 72 27390064 Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors. The V108I mutant is known to shift the position of residue Y188, which may directly affect binding of the 7-azaindole core, as that RT mutant was resistant to inhibition at the highest tested concentration of all three compounds. 2016 Bioorganic & medicinal chemistry letters Introduction HIV V108I 4 9 RT 132 134 27473196 Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV". Paul identified significant impairments in cognitive function in HIV-positive individuals compared to HIV-negative individuals independent of the Tat mutation (C31S). 2016 Journal of neurovirology Introduction HIV C31S 160 164 Tat 146 149 27473196 Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV". Tat from Clade C virus has a polymorphism at C31S. 2016 Journal of neurovirology Introduction HIV C31S 45 49 Tat 0 3 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. It is of note, however, that RAL-resistant HIV-1 variants selected with RAL, that have acquired both Q148/H/K and/or N155H substitutions in IN, are cross-resistant to EVG. 2016 Journal of virological methods Introduction HIV N155H 117 122 IN 140 142 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. Recently, the French PRIMO cohort study detected isolated E157Q mutations in 1.5% of baseline samples 16. 2017 HIV medicine Introduction HIV E157Q 58 63 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. Although these compounds and many others have shown promising inhibitory activity, various resistance mutations, including the A128T IN mutation, have been observed for many of the reported quinoline-based ALLINIs. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 127 132 IN 133 135 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. As predicted by the computational docking model, the five-membered indole ring structure of 5c mitigates the repulsion induced by the A128T mutation by tilting the aromatic ring away from the 128 residue of subunit 1, thus maintaining similar activities against both the WT and A128T proteins. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T;A128T 134;278 139;283 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. Due to the similarity in activity to the quinoline-based ALLINIs, 5c was also screened against the single amino-acid A128T substitution in HIV-1 IN that confers marked resistance to quinoline-based inhibitors, including BI-1001. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 117 122 IN 145 147 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. In contrast, very similar binding orientations of 5c have been observed in both the wild type and A128T CCD-CCD (Figure 3C) crystal structures. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 98 103 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. In sharp contrast to BI-1001, 5c promoted aberrant multimerization of both wild type and the A128T mutant INs with similar IC50 values (Figure 2). 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 93 98 IN 106 109 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. Likewise, 5c also showed similar inhibition of 3'-processing activity in both the wild type and A128T mutant with IC50 values of 3.2 and 0.9 muM, respectively. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 96 101 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. The five-membered indole ring, however, allows this class of compounds to avoid steric and electrostatic repulsions by the A128T substitution that leads to marked resistance to many quinoline-based ALLINIs. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 123 128 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. To understand the structural basis for the mode of action of indole-based compounds the crystal structures of 5c bound to both the wild type and A128T IN CCDs have been solved. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 145 150 IN 151 153 27568085 Indole-based allosteric inhibitors of HIV-1 integrase. While the key acetic acid and aryl substituents are predicted to overlay well in both the quinoline and indole systems, a slight "tilt" of the indole aromatic ring away from the A128 residue relative to the quinoline ring system is observed, suggesting that the indole analogues may not interact with that site or be affected by the A128T mutation which confers marked resistance to quinoline-based ALLINI analogues. 2016 Bioorganic & medicinal chemistry letters Introduction HIV A128T 333 338 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. As shown in Table 4, knocking out of these glycan residues was found to be correlated significantly with increased susceptibility of the NLR-2007.J12 Env (N139A/N142A/N145gA, N145lA/N147A) with longer V1 loop to PGT121 and PGT128 mAbs by >20 and >35 folds respectively. 2016 Retrovirology Introduction HIV N139A;N142A;N147A 155;161;182 160;166;187 Env 150 153 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. As shown in Table 4, while HIV-1 NLR-2007.J12 expressing V1 region of HIV-1 NLR-2007.J48 (S332N) (shorter V1 loop) became sensitive to both PGT121 and PGT128 mAbs; HIV-1 NLR-2007.J48 (S332N) containing V1 loop of the HIV-1 NLR-2007.J12 Env became resistant to the PGT121 and PGT128 mAbs by >17 and >100-fold respectively. 2016 Retrovirology Introduction HIV S332N;S332N 90;184 95;189 Env 236 239 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. However, a 2.42 and >5-fold reduction in neutralization of the two Env-pseudotyped viruses (25711-2.4 and CAP239.G3) with N301A and N332A substitutions in V3 respectively compared to their wild types were observed (Table 2B). 2016 Retrovirology Introduction HIV N301A;N332A 122;132 127;137 Env;Capsid 67;106 70;108 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. However, only 1.9-fold increase in neutralization of NLR-2007.J12 (N139A/N142A/N145gA, N145lA/N147A) to autologous plasma antibodies was observed. 2016 Retrovirology Introduction HIV N139A;N142A;N147A 67;73;94 72;78;99 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. In order to determine whether longer V1 loop length was associated with neutralization resistance of autologous Envs to N332 directed neutralizing antibodies, we next exchanged the V1 domain between HIV-1 NLR-2007.J48 (S332N) and HIV-1 NLR-2007.J12 and examined susceptibility to the INDO-SA 2007 plasma, PGT121 and PGT128 mAbs. 2016 Retrovirology Introduction HIV S332N 219 224 Env 112 116 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. In summary, our data provide evidence that the circulating HIV-1 clade C in this elite neutralizer escaped the neutralization by the autologous plasma in this patient via three distinct mechanisms: (1) due to a N332S mutation (2) by increasing V1 loop length and (3) incorporation of protective N-glycan residues in V1 loop. 2016 Retrovirology Introduction HIV N332S 211 216 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. Thus, while the N332S mutation mediated neutralization resistance of HIV-1 NLR-2007.J48 Env, the other contemporaneous Envs despite naturally expressing N332 were found not to be susceptible to N332-specific neutralizing antibodies including PGT121 and PGT128, possibly due to attaining a distinct conformation that prevented accessing the N332 glycan epitope by these potent neutralizing antibodies. 2016 Retrovirology Introduction HIV N332S 16 21 Env;Env 88;119 91;123 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. Upon substituting the naturally occurring serine residue with a glycan at the 332 position (S332N), the sensitivity of the HIV-1 NLR-2007.J48 Env to autologous plasma, PGT121 and PGT128 mAbs was found to increase by 10, >80 and >100 folds respectively (Table 4). 2016 Retrovirology Introduction HIV S332N 92 97 Env 142 145 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. In the context of the NL4-3 strain of HIV-1, S40A altered sensitivity to the protease (PR) inhibitor Indinavir (IDV). 2016 Retrovirology Introduction HIV S40A 45 49 PR;PR 77;87 85;89 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The alanine (A) substitution (S40A), where TCC = S to GCC = A, in contrast, had a less deleterious effect on Gag processing, polyubiquitination or particle maturation morphology but altered the sequence at the p6*/PR cleavage site in the overlapping pol frame. 2016 Retrovirology Introduction HIV S40A 30 34 Pol;Gag;Gag;PR 250;109;210;214 253;112;212;216 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The S40A change in the gag frame is accompanied by an F to C change at the N-terminus of PR in the overlapping pol frame resulting in GTVSFN (or S) C/PQITLWQ. 2016 Retrovirology Introduction HIV S40A 4 8 Pol;Gag;PR 111;23;89 114;26;91 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The substitution of F (S40F), where TCC = S to TTC = F, does not alter the sequence of the overlapping pol frame (TTC = F in the WT to TTT = F) but had an impact on several aspects of gag function. 2016 Retrovirology Introduction HIV S40F 23 27 Pol;Gag 103;184 106;187 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Two substitutions that occurred at the same residue, S40F and S40A, were further investigated by engineering the individual substitutions into an HIV genome (pNL4-3). 2016 Retrovirology Introduction HIV S40A;S40F 62;53 66;57 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Additionally K65R mutation selected by TDF, ABC, d4T, and DDI impart resistance to all NRTI except AZT. 2016 Medicine Introduction HIV K65R 13 17 NRTI 87 91 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Conventionally, mutations like K69 Insertion, Q151M complex and multiple TAMs reduce susceptibility to all currently available NRTI. 2016 Medicine Introduction HIV Q151M 46 51 NRTI 127 131 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. In combination with TAMs, M184V also reduces susceptibility to ABC and DDI. 2016 Medicine Introduction HIV M184V 26 31 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. In one of the prior large study involving genotyping of 138 patients with failure from South India, M184V and Y181C emerged as most common NRTI and NNRTI mutations, respectively. 2016 Medicine Introduction HIV M184V;Y181C 100;110 105;115 NNRTI;NRTI 148;139 153;143 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. In subtype C-infected Indian population, K69 Insertion and Q151M are seldom reported and common mutations responsible for multi-NRTI resistance includes, K65R and multiple TAMs with or without M184V. 2016 Medicine Introduction HIV K65R;M184V;Q151M 154;193;59 158;198;64 NRTI 128 132 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. M184V is selected by 3TC/FTC and reduces susceptibility to these drugs by 100-fold. 2016 Medicine Introduction HIV M184V 0 5 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. A hypothesis has been proposed to elucidate the resistance mechanism from the K103N substitution. 2016 Viruses Introduction HIV K103N 78 83 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. A relatively rare mutation of Y188L was also identified in viruses from patients who have failed with NNRTI-containing regimens. 2016 Viruses Introduction HIV Y188L 30 35 NNRTI 102 107 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Another prevalent NNRTI-resistant mutation is Y181C substitution, which is present in 15%-25% of NNRTI-resistant viruses. 2016 Viruses Introduction HIV Y181C 46 51 NNRTI;NNRTI 18;97 23;102 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. As a result, it is hypothesized that the resistance of Y181C and Y188L RT mutations is attributed to the loss of pi-pi stacking of aromatic rings between the residues and NNRTIs. 2016 Viruses Introduction HIV Y181C;Y188L 55;65 60;70 NNRTI;PI;PI;RT 171;113;116;71 177;115;118;73 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Comparison of the structures between the unliganded WT and K103N RT reveal a network of hydrogen bonds in the K103N mutant that is not present in the WT enzyme. 2016 Viruses Introduction HIV K103N;K103N 59;110 64;115 RT 65 67 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Examination of the structures of the K103N RT/NNRTI complexes shows that the K103N substitution induces only minor positional adjustments of the NNRTIs and residues in the binding pocket:when compared with structures of wild type (WT) RT/NNRTI complexes. 2016 Viruses Introduction HIV K103N;K103N 37;77 42;82 NNRTI;NNRTI;NNRTI;RT;RT 46;145;238;43;235 51;151;243;45;237 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. In particular, a hydrogen bond in the unliganded K103N RT (but not in WT RT) was observed between N103 and Y188. 2016 Viruses Introduction HIV K103N 49 54 RT;RT 55;73 57;75 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Instead, electrostatic interaction may play a more important role in conferring the resistance of the K103N mutant/RT to the first-generation NNRTIs. 2016 Viruses Introduction HIV K103N 102 107 NNRTI;RT 142;115 148;117 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Moreover, Y181F, Y188F, and Y181F/Y188F mutant RTs were generated to directly test the significance of pi-pi stacking on the NNRTIs' affinity to the binding pocket. 2016 Viruses Introduction HIV Y181F;Y181F;Y188F;Y188F 10;28;17;34 15;33;22;39 NNRTI;PI;PI;RT 125;103;106;47 131;105;108;50 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. No hydrogen bond between F188 and N103 can be formed with the Y188F/K103N substitutions, as there is no hydroxyl group in phenylalanine. 2016 Viruses Introduction HIV K103N;Y188F 68;62 73;67 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The K103N mutant is the most common mutation associated with NNRTIs, which is estimated to be present in 40%-60% of NNRTI-resistant viruses. 2016 Viruses Introduction HIV K103N 4 9 NNRTI;NNRTI 61;116 67;121 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The purpose of this study was to investigate the mechanism of resistance conferred by the two most prevalent NNRTI mutations with K103N and Y181C substitutions. 2016 Viruses Introduction HIV K103N;Y181C 130;140 135;145 NNRTI 109 114 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Therefore, the K103N substitution will reduce the affinity to NNRTIBP, if NNRTIs rely on the hydrophobic interactions for their potencies. 2016 Viruses Introduction HIV K103N 15 20 NNRTI 74 80 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. To determine if the hydrogen bond between N103 and Y188 contributes to the resistance of K103N substitution, the tyrosine (Y) at 188 was replaced with phenylalanine (P). 2016 Viruses Introduction HIV K103N;Y188Y 89;110 94;135 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. To facilitate the development of better NNRTIs, it is important to understand the resistance mechanisms of the prevalent mutations; especially those arising from the K103N and Y181C substitutions in RT. 2016 Viruses Introduction HIV K103N;Y181C 166;176 171;181 NNRTI;RT 40;199 46;201 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Y188L was shown to be highly resistant to first-generation NNRTIs such as EFV and NVP. 2016 Viruses Introduction HIV Y188L 0 5 NNRTI 59 65 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Along with neutralization sensitivity, we have identified a mutation (I37K) in the gp120-gp41 interactive region of gp41 HR1 that has a global impact on the different antigenic sites on the HIV-1 envelope. 2016 Retrovirology Introduction HIV I37K 70 74 Env;gp120;gp41;gp41 196;83;89;116 204;88;93;120 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. Two of these mutants, N155H and G140S/Q148H, also had, relative to WT HIV-1, a reduced susceptibility to EVG, and to other INSTIs. 2016 Retrovirology Introduction HIV G140S;N155H;Q148H 32;22;38 37;27;43 INSTI 123 129 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. We tested the effects of three IN mutations, Y143R, N155H, and the double mutation G140S/Q148H, all of which reduce the susceptibility of HIV-1 to RAL, on viral DNA integration. 2016 Retrovirology Introduction HIV G140S;N155H;Q148H;Y143R 83;52;89;45 88;57;94;50 IN 31 33 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. This clone encodes an Env protein with a full cytoplasmic tail (158 amino acids) and does not harbor the I312T or V536L substitutions observed in the ROD10 molecular clone. 2016 Viruses Introduction HIV I312T;V536L 105;114 110;119 Env 22 25 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. With one or two major mutations, such as Q148HKR +- G140SA, N155H +- E92Q or Y143CR +- T97A, a marked reduction of viral susceptibility to raltegravir and elvitegravir has been observed. 2016 Scientific reports Introduction HIV E92Q;G140A;G140S;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143R 69;52;52;60;41;41;41;87;77;77 73;58;58;65;48;48;48;91;83;83 27790293 Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans. On the other hand, the EcoR1 restriction site exists due to a change in guanidine to adenine at exon 29 (GAA AAA), leading to the substitution of glutamine for lysine at position 4154 in the ApoB polypeptide product (p.Gln4154Lys). 2016 The open AIDS journal Introduction HIV K4154Q;Q4154K 146;217 183;229 27790293 Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans. This base change creates a cutting site for the restriction endonuclease Xba1 and the polymorphism is known as APOB 2488C>T Xba1 polymorphism (-7673C T). 2016 The open AIDS journal Introduction HIV C2488T 116 123 27790293 Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans. This nucleotide change leads to loss of the EcoR1 restriction site and the polymorphism is known as APOB 4154G>A polymorphism (-2669G A). 2016 The open AIDS journal Introduction HIV G4154A 105 112 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. As JRCSF Env is efficiently cleaved and can bind preferentially to all the different classes of quaternary epitope-dependent but glycan directed bNAbs when expressed on the cell surface, it may be better suited for use as a platform for designing immunogen due to its ability to bind to bNAbs targeting the trimer-specific V2 "cap" while retaining its ability to bind CD4-bs-directed bNAbs through the N197D mutation. 2016 Retrovirology Introduction HIV N197D 402 407 Env 9 12 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. JRCSF (N197D) appears to bind more efficiently to CD4-bs-directed NAbs than JRFL while JRCSF binds to PG9/PGT145 class of antibodies more efficiently than JRFL (E168K). 2016 Retrovirology Introduction HIV E168K;N197D 161;7 166;12 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Purified BG505SOSIP.664 (MPER deleted and contains the T332N substitution) forms a cleaved, trimeric, native-like Env protein that binds preferentially to bNAbs but generally not to non-NAbs. 2016 Retrovirology Introduction HIV T332N 55 60 Env 114 117 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. This problem has been circumvented by generating SOSIP versions (containing A501C, T605C, I559P mutations in BG505) of the cleaved, C-terminus truncated Env glycoprotein to aa664 and purifying the trimeric form. 2016 Retrovirology Introduction HIV A501C;I559P;T605C 76;90;83 81;95;88 Env 153 156 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. An E12A mutant that was designed to eliminate this salt bridge was tested for trimer formation and virus release efficiency. 2016 PloS one Introduction HIV E12A 3 7 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. E12A retained similar efficiency for virus release compared to wild-type (WT) protein, whereas the E12A mutation abolished trimer-forming activity, even in the presence of a myristyl group at the N-terminus. 2016 PloS one Introduction HIV E12A;E12A 99;0 103;4 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Furthermore, more significant conformational exchanges were observed at the alpha1-2 loop and helix 5 in E12A compared to WT. 2016 PloS one Introduction HIV E12A 105 109 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Importantly, the existence of a more flexible motion at the regions of each loop for WT, compared to that of E12A, was observed through order parameter analyses. 2016 PloS one Introduction HIV E12A 109 113 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In addition, fluctuations on a slower time scale were monitored by phase-modulated clean chemical exchange (CLEANEX-PM) for the quick exchange of amide protons using E12A as well as L85A. 2016 PloS one Introduction HIV E12A;L85A 166;182 170;186 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In the present study, first of all, the interaction between E12 and H89 in the p17 structure was confirmed by the chemical shift perturbation studies using E12A and L85A. 2016 PloS one Introduction HIV E12A;L85A 156;165 160;169 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. It was concluded that the formation of the trimer of p17 was either promoted by the flexible motions existing at loop regions in the WT protein or interrupted by unfavorable conformational exchanges in E12A. 2016 PloS one Introduction HIV E12A 202 206 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Next, the dynamic structure of E12A was analyzed by T1, T2, and heteronuclear NOE experiments. 2016 PloS one Introduction HIV E12A 31 35 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The exposure of a myristyl group, which can be correlated to membrane-binding activity, has been tested using mutants including V7R, L8A, L8I, and L21K. 2016 PloS one Introduction HIV L21K;L8A;L8I;V7R 147;133;138;128 151;136;141;131 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Behaviorally, mice injected with C31S perform better on memory tests compared to mice injected with C31C virus, revealing a functional benefit of the HIV-C Tat polymorphism. 2017 Journal of neurovirology Introduction HIV C31C;C31S 100;33 104;37 Tat 156 159 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Further, since structural MRI and DTI are not confounded by the same limitations inherent in neuropsychological testing (e.g., participant effort), the methods provide a robust approach to determine the relevance of the Tat C31S polymorphism in patient samples. 2017 Journal of neurovirology Introduction HIV C31S 224 228 Tat 220 223 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. More recently, our group compared cognitive performances between HIV-C individuals with and without the Tat C31S polymorphism and reported no significant differences in the cognitive phenotype or severity of cognitive impairment by Tat status. 2017 Journal of neurovirology Introduction HIV C31S 108 112 Tat;Tat 104;232 107;235 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. The present study examined the neurovirulence of the two HIV-C Tat variants (C31C and C31S) using structural MRI and DTI. 2017 Journal of neurovirology Introduction HIV C31C;C31S 77;86 82;90 Tat 63 66 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. The reduced neurovirulence of HIV-C has been attributed to a naturally occurring cysteine to serine substitution at position 31 (C31S) in the HIV-C Tat protein that is highly conserved in HIV-C. 2017 Journal of neurovirology Introduction HIV C31S;C31S 129;81 133;127 Tat 148 151 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. The Tat C31S substitution results in reduced monocyte chemotaxis, astrogliosis, pro-inflammatory cytokines, and neuronal damage when compared to assays using HIV-B with a C31C Tat motif. 2017 Journal of neurovirology Introduction HIV C31C;C31S 171;8 175;12 Tat;Tat 4;176 7;179 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. We predicted that if present, the biological relevance of C31S would be defined by a unique neuroimaging signature on volumetric and diffusion indices. 2017 Journal of neurovirology Introduction HIV C31S 58 62 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. ACTG 244 began enrollment in February 1994, and among the 289 enrollees, 284 were dispensed ZDV, of whom 57 developed T215Y/F. 2017 Biometrics Introduction HIV T215F;T215Y 118;118 125;125 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. ACTG 244 enrolled subjects receiving ZDV monotherapy and monitored their HIV in plasma bi-monthly for the T215Y/F mutation. 2017 Biometrics Introduction HIV T215F;T215Y 106;106 113;113 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. ACTG 244 was a randomized, double-blind trial that evaluated the clinical utility of monitoring HIV infected patients taking Zidovudine (ZDV) monotherapy for occurrence of the T215Y/F ZDV resistance mutation. 2017 Biometrics Introduction HIV T215F;T215Y 176;176 183;183 HIV infections 96 108 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. An additional reason is that the time to develop the T215Y/F mutation introduces informative censoring, and thus our analysis of the second randomization strategy that only includes subjects who did not develop the mutation avoids making a false assumption of non-informative censoring. 2017 Biometrics Introduction HIV T215F;T215Y 53;53 60;60 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. First, we examine the effects of switching treatments following detection of the T215Y/F mutation. 2017 Biometrics Introduction HIV T215F;T215Y 81;81 88;88 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. In addition, Section 7.1 focuses on the treatment comparison in subjects who acquired the T215Y/F mutation; the time of the second randomization is treated as the censoring time for the 137 subjects who did not develop the mutation and were randomized at the interim review. 2017 Biometrics Introduction HIV T215F;T215Y 90;90 97;97 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. In this section, we examine the effects of this switching of treatments before the T215Y/F mutation was detected. 2017 Biometrics Introduction HIV T215F;T215Y 83;83 90;90 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. Let S1 be the time from study entry until the first randomization based on occurrence of the T215Y/F mutation (the treatment switching time), where we set S1 = 3 years, a number longer than the study duration, for subjects who did not experience the mutation. 2017 Biometrics Introduction HIV T215F;T215Y 93;93 100;100 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. Of the 227 subjects who remained on ZDV treatment without the T215Y/F mutation, 137 were still taking ZDV at the time of the interim review and were randomized to ZDV+ddI (n=69) or ZDV+ddI+NVP (n=68); the remaining 90 subjects went off treatment prior to the interim review. 2017 Biometrics Introduction HIV T215F;T215Y 62;62 69;69 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. T215Y/F mutation status was determined by RT-PCR and was measured at study entry and every 8 weeks thereafter, with variability in visit dates across individuals. 2017 Biometrics Introduction HIV T215F;T215Y 0;0 7;7 RT 42 44 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. The 90 subjects who were off treatment prior to the interim review without having the T215Y/F mutation are censored at the time of drop-off. 2017 Biometrics Introduction HIV T215F;T215Y 86;86 93;93 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. The estimated switching-treatment effects and 95% confidence intervals are above zero, suggesting that switching to ZDV+ddI or ZDV+ddI+NVP improves CD4 counts for patients who had not yet developed the T215Y/F drug resistance mutation. 2017 Biometrics Introduction HIV T215F;T215Y 202;202 209;209 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. The main reason for the separate analyses rather than a single combined analysis is that the study populations for inference are fundamentally different, given the large impact of the T215F/Y drug resistance mutation on CD4 cell count. 2017 Biometrics Introduction HIV T215F;T215Y 184;184 191;191 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. Then U1(t) = t - S1 is the time elapsed from the T215Y/F mutation-based treatment randomization. 2017 Biometrics Introduction HIV T215F;T215Y 49;49 56;56 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. This analysis excludes subjects who developed the T215Y/F mutation to allow answering the study question for the sub-population without the mutation and because the time to develop T215Y/F likely introduces dependent censoring. 2017 Biometrics Introduction HIV T215F;T215F;T215Y;T215Y 50;181;50;181 57;188;57;188 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. ZDV+ddI+NVP in subjects taking ZDV who did not have the T215Y/F mutation. 2017 Biometrics Introduction HIV T215F;T215Y 56;56 63;63 27918612 Generalized semiparametric varying-coefficient model for longitudinal data with applications to adaptive treatment randomizations. ZDV+ddI+NVP in subjects who acquired the T215Y/F mutation, and the second comparing ZDV+ddI vs. 2017 Biometrics Introduction HIV T215F;T215Y 41;41 48;48 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Solution NMR studies were carried out to investigate the open-closed flap conformation of the inhibitor free PRS17 bearing an active site D25N mutation. 2016 PloS one Introduction HIV D25N 138 142 PR 109 111 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. In addition, we identified a mutation in Vif, K26R, which abolishes degradation of A3G by the proteasome but has no effect on the translational repression of A3G, demonstrating that these two pathways are independent. 2016 Scientific reports Introduction HIV K26R 46 50 Vif 41 44 28195728 Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K. In a few instances, however, drug resistant mutations lead to possible formation of unfavorable interactions, with a stark example of saquinavir-specific substitution G48V. 2017 Journal of medicinal chemistry Introduction HIV G48V 167 171 28195728 Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K. In this work, we report a room temperature XN structure of the PR triple mutant variant V32I/I47V/V82I (referred to as PRTM henceforth) in complex with APV at pH 6.0 (PDB ID 5T8H), and compare it to the room temperature XN structure of PRWT-APV complex and to the low temperature PRTM-APV X-ray structure. 2017 Journal of medicinal chemistry Introduction HIV I47V;V32I;V82I 93;88;98 97;92;102 PR 63 65 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Across multiple clinical studies, T97A has been periodically co-selected in the presence of primary INSTI RAMs by RAL and EVG. 2017 PloS one Introduction HIV T97A 34 38 INSTI 100 105 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. As a secondary INSTI RAM, T97A further reduces INSTI susceptibility and/or rescues viral fitness in association with Y143C/R, Q148H+G140S, or N155H. 2017 PloS one Introduction HIV G140S;N155H;Q148H;T97A;Y143C;Y143R 132;142;126;26;117;117 137;147;131;30;124;124 INSTI;INSTI 15;47 20;52 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Depending on subtype, T97A generally pre-exists in 1-5% of INSTI-naive HIV-infected individuals with some exceptions (subtype A: 5-10%; subtype J: 33%; group P: 50%), yet has also been associated with emergent INSTI resistance in patients experiencing virologic failure on RAL or EVG. 2017 PloS one Introduction HIV T97A 22 26 INSTI;INSTI 59;210 64;215 HIV infections 71 83 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, despite the fact that some patients may harbor T97A before INSTI-based treatment, little is known about the clinical and prognostic implications of this naturally occurring resistance-associated integrase polymorphism. 2017 PloS one Introduction HIV T97A 56 60 IN;INSTI 204;68 213;73 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In rare cases, T97A has also been selected alone (i.e., in the absence of primary INSTI RAMs) by RAL and EVG, which led us to previously consider T97A alone as a special case of primary INSTI RAM that requires additional integrase mutations (Fig 1). 2017 PloS one Introduction HIV T97A;T97A 15;146 19;150 IN;INSTI;INSTI 221;82;186 230;87;191 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In this study, the prevalence of T97A was evaluated as a pre-existing or emergent integrase mutation relative to its impact on INSTI susceptibility and treatment outcome in HIV-infected patients enrolled on EVG- or RAL-based regimens. 2017 PloS one Introduction HIV T97A 33 37 IN;INSTI 82;127 91;132 HIV infections 173 185 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Indeed, while T97A alone confers low-level to no effect on EVG and RAL susceptibility, respectively, additional integrase polymorphism(s) such as V72I, L74M, and/or G163R may serve a role to further reduce INSTI susceptibility before or during INSTI-based treatment. 2017 PloS one Introduction HIV G163R;L74M;T97A;V72I 165;152;14;146 170;156;18;150 IN;INSTI;INSTI 112;206;244 121;211;249 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. T97A has also been selected by DTG in TE patients with pre-existing primary RAL RAMs. 2017 PloS one Introduction HIV T97A 0 4 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The T97A integrase mutation is an HIV-1 integrase polymorphism of interest to clinicians considering INSTI-based therapy for HIV-infected patients under their care. 2017 PloS one Introduction HIV T97A 4 8 IN;IN;INSTI 9;40;101 18;49;106 HIV infections 125 137 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. This is particularly important as T97A could change the guideline recommendation for pre-treatment integrase genotyping to include all patients, regardless of suspected INSTI transmitted drug resistance. 2017 PloS one Introduction HIV T97A 34 38 IN;INSTI 99;169 108;174 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Whether the appearance of T97A is natural or transmitted, it is currently unclear if HIV-infected patients with pre-existing T97A are at risk to delayed virologic suppression or earlier virologic failure and the development of INSTI resistance. 2017 PloS one Introduction HIV T97A;T97A 26;125 30;129 INSTI 227 232 HIV infections 85 97 28328548 Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT. M184I/V drug resistance mutations, which confer resistance to FTC, are seen more commonly in the setting of PrEP than the K65R mutation, which confers resistance to TDF. 2017 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K65R;M184I;M184V 122;0;0 126;7;7 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. We noted a worrying rise in the detection of NNRTI-mutation K103N, which compromises the efficacy of the WHO-recommended first-line regimen. 2017 Clinical infectious diseases Introduction HIV K103N 60 65 NNRTI 45 50 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Although the RT mutation K65R seems to be selected in HIV-1 and HIV-2 after exposure to tenofovir and other NRTIs, our results suggest that there is limited functional equivalence between Lys65 in both HIV RTs. 2017 Scientific reports Introduction HIV K65R 25 29 NRTI;RT;RT 108;13;206 113;15;209 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. An estimated prevalence of 9% has been reported for the combination of K65R, Q151M and M184V in a European cohort of HIV-2-infected patients treated with antiretroviral drugs. 2017 Scientific reports Introduction HIV K65R;M184V;Q151M 71;87;77 75;92;82 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. As previously shown in HIV-1, K65R arises in HIV-2-infected patients exposed to tenofovir and other NRTIs, while M184V confers high-level resistance to approved cytidine analogues. 2017 Scientific reports Introduction HIV K65R;M184V 30;113 34;118 NRTI 100 105 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. By themselves, amino acid substitutions K65R, Q151M or M184V in HIV-1 RT confer reduced catalytic efficiency of nucleotide analogue incorporation (review). 2017 Scientific reports Introduction HIV K65R;M184V;Q151M 40;55;46 44;60;51 RT 70 72 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Consistently with those findings, mutant HIV-1 with RT substitutions K65R or M184V show delayed replication kinetics in comparison with the wild-type (WT) virus. 2017 Scientific reports Introduction HIV K65R;M184V 69;77 73;82 RT 52 54 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Furthermore, the error rates of mutant RTs K65R and K65R/Q151M/M184V were similar to those obtained with the WT HIV-2 RT, using an M13mp2 lacZalpha forward mutation assay. 2017 Scientific reports Introduction HIV K65R;M184V;Q151M;K65R 52;63;57;43 56;68;62;47 RT;RT 39;118 42;120 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. HIV-1 RTs with Arg65 instead of Lys showed decreased nucleotide incorporation rates (kpol) in pre-steady-state kinetic assays. 2017 Scientific reports Introduction HIV R65K 15 35 RT 6 9 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In addition, K65R confers low-level resistance to didanosine and moderate to high-level resistance to lamivudine and emtricitabine in HIV-2 strains. 2017 Scientific reports Introduction HIV K65R 13 17 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In agreement with enzymatic data, K65R produced a 3.3-fold mutant frequency reduction in single round of replication assays, using an HIV-1NL43 vector containing the lacZ gene. 2017 Scientific reports Introduction HIV K65R 34 38 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In our study, we have examined the effects of K65R, Q151M and M184V on nucleotide incorporation, using pre-steady-state kinetics. 2017 Scientific reports Introduction HIV K65R;M184V;Q151M 46;62;52 50;67;57 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In the case of M184V, the fitness defect is more pronounced at low dNTP concentrations and is expected to be more relevant for viruses replicating in non-dividing cells (e.g. 2017 Scientific reports Introduction HIV M184V 15 20 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. K65R can be selected in vitro after HIV-2 exposure to increasing doses of tenofovir and produces a 2- to 7-fold decrease in viral susceptibility to the drug. 2017 Scientific reports Introduction HIV K65R 0 4 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. L74V, E89G, V111I, S215Y, L74V/S215Y and E89G/S215Y), whose effects were evaluated for a small subset of misincorporations or mispairs using nucleotide discrimination assays. 2017 Scientific reports Introduction HIV E89G;E89G;L74V;S215Y;S215Y;S215Y;V111I;L74V 6;41;26;19;31;46;12;0 10;45;30;24;36;51;17;4 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. None of the studied residues were part of the complex conferring multi-NRTI resistance, although sometimes V111I appears as an accessory mutation that compensates for the lower fitness of classwide NRTI-resistant HIV-2. 2017 Scientific reports Introduction HIV V111I 107 112 NRTI;NRTI 71;198 75;202 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Other studies have shown that K65R produces a >8-fold increase in the intrinsic fidelity of the HIV-1 RT, an effect that has been demonstrated with RTs of highly divergent HIV-1 group M (subtype B) and group O strains. 2017 Scientific reports Introduction HIV K65R 30 34 RT;RT 102;148 104;151 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Phenotypic studies using recombinant HIV-2 have shown that Q151M alone confers high-level resistance to AZT (zidovudine), and moderate- to low-level resistance to stavudine, abacavir, didanosine and emtricitabine. 2017 Scientific reports Introduction HIV Q151M 59 64 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. RT substitutions K65R and Q151M are frequently identified in virus obtained from treated HIV-2-infected patients, and the presence of both changes together with M184V confers classwide NRTI resistance. 2017 Scientific reports Introduction HIV K65R;M184V;Q151M 17;161;26 21;166;31 NRTI;RT 185;0 189;2 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Unexpectedly, and unlike in the case of HIV-1 RTs, K65R had a relatively small impact on misinsertion and mispair extension ratios suggesting only subtle effects on the fidelity of HIV-2 RT. 2017 Scientific reports Introduction HIV K65R 51 55 RT;RT 46;187 49;189 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Unlike HIV-1, HIV-2 does not develop resistance to nucleoside RT inhibitors (NRTIs) through the excision pathway (involving amino acid substitutions M41L, D67N, K70R, L210W, T215F/Y and K219E/Q in the viral RT), but relies exclusively on nucleotide discrimination. 2017 Scientific reports Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 155;186;186;161;167;149;174;174 159;193;193;165;172;153;181;181 NRTI;RT;RT 77;62;207 82;64;209 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. We show that WT and mutant HIV-2 RTs have reduced nucleotide binding affinities in comparison with the equivalent HIV-1 enzymes, while M184V was found to be responsible for the reduced catalytic efficiency of the triple mutant K65R/Q151M/M184V. 2017 Scientific reports Introduction HIV K65R;M184V;Q151M;M184V 227;238;232;135 231;243;237;140 RT 33 36 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. F1Pk aptamers fail to inhibit RT from most other subtypes when tested against a panel of phylogenetically diverse RTs in biochemical assays, and a single point mutation (R277K) was sufficient to abolish inhibition by F1Pk aptamers. 2017 Nucleic acids research Introduction HIV R277K 170 175 RT;RT 30;114 32;117 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. In support of this idea, RT mutations N255D and N265D, which confer resistance to DNA aptamer RT1t49 in enzymatic assays, were shown to induce processivity defects and to impair replication when introduced into viruses. 2017 Nucleic acids research Introduction HIV N255D;N265D 38;48 43;53 RT 25 27 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. It is not known, however, whether K65R/N and K70E/G/Q represent the full spectrum of NRTI-associated mutations in individuals receiving a WHO-recommended first-line TDF-containing regimen. 2017 EBioMedicine Introduction HIV K65N;K65R;K70E;K70G;K70Q 34;34;45;45;45 40;40;53;53;53 NRTI 85 89 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. We recently performed a meta-analysis which showed that between 20% to 60% of individuals with VF on a TDF-containing regimen developed genotypic evidence of TDF resistance defined as the presence of either K65R/N or K70E/G/Q in the HIV-1 reverse transcriptase (RT) gene (TenoRes Study). 2017 EBioMedicine Introduction HIV K65N;K65R;K70E;K70G;K70Q 207;207;217;217;217 213;213;225;225;225 RT;RT 239;262 260;264 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Altogether, those results suggest that R263K preferentially emerges upon ab initio DTG pressure and also points toward the potential involvement of residual replication in the emergence of drug resistance (discussed in reference). 2017 mBio Introduction HIV R263K 39 44 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. As remarkable was the absence of R263K in viruses isolated from individuals who experienced failure with DTG monotherapy. 2017 mBio Introduction HIV R263K 33 38 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Here we investigated how the defect in integration associated with R263K affects HIV-1 DNA levels during prolonged infections in tissue culture. 2017 mBio Introduction HIV R263K 67 72 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In addition, treatment failure in such individuals was associated with the presence of various RAL/EVG resistance substitutions that predated DTG use, most notably at positions Q148 and N155H. 2017 mBio Introduction HIV N155H 186 191 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In contrast to resistance pathways that develop with RAL or EVG, we found no compensatory mutation for R263K under DTG selective pressure. 2017 mBio Introduction HIV R263K 103 108 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In treatment-experienced INSTI-naive individuals, DTG failure can be associated with the emergence of the R263K integrase substitution, whereas INSTI-experienced individuals can experience failure with a variety of mutations commonly associated with RAL or EVG failure. 2017 mBio Introduction HIV R263K 106 111 IN;INSTI;INSTI 112;25;144 121;30;149 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Molecular modeling further suggested that R263K indirectly alters the conformation of the integrase catalytic site through a cascade of amino acid interactions. 2017 mBio Introduction HIV R263K 42 47 IN 90 99 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Our results show that R263K does not affect reverse transcription and leads to a progressive decline in HIV-1 integrated DNA over time in prolonged infections. 2017 mBio Introduction HIV R263K 22 27 RT 44 65 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Short-term infections (24 to 72 h) have confirmed that R263K reduces the levels of integrated HIV type 1 (HIV-1) DNA compared to wild-type (WT) virus. 2017 mBio Introduction HIV R263K 55 60 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. We have extensively characterized the R263K substitution and showed that it decreases HIV integrase strand transfer activity at least in part by decreasing integrase DNA binding activity as measured in cell-free assays. 2017 mBio Introduction HIV R263K 38 43 IN;IN 90;156 99;165 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. For reasons that are not entirely clear, it seems that the genetic barrier to K65R development is not as low as with some other NRTIs and NNRTIs. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 78 82 NNRTI;NRTI 138;128 144;133 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. However, additional data to support the reported subtype-dependent selection of K65R is needed especially if it can clearly distinguish between the influence of subtype, exposure groups and ethnicity. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 80 84 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. It is well established that the M184V mutation develops quickly in patients failing on emtricitabine/lamivudine, which is not the case for K65R even though it requires only a single nucleotide A-G change at reverse transcriptase (RT) codon 65 to cause the lysine to arginine amino acid change. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R;M184V 139;32 143;37 RT;RT 207;230 228;232 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. K65R is the signature mutation associated with tenofovir resistance and also confers significant cross-resistance to abacavir, didanosine and stavudine. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 0 4 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Some retrospective cohort studies that have looked at factors associated with the emergence of K65R have identified subtype C to be a predictive factor. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 95 99 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Subtype C viruses are more likely to develop K65R mutations in patients with virological failure than other HIV-1 subtypes. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 45 49 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The low prevalence of K65R seen in clinical trials and in various resistance databases would support the premise that K65R does not develop that easily in settings where virological failure is well controlled. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R;K65R 22;118 26;122 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The UK national database is well placed to differentiate between these factors as it collects diverse HIV resistance and subtype data typical of the UK HIV epidemic and the aim of this study was to undertake a direct comparative analysis and to determine whether K65R is detected more frequently in subtype C viruses at virological failure. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 263 267 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The wide variation in K65R prevalence is most likely explained by different standards of care, with slower switching after virological failure allowing for greater accumulation of drug resistance to all classes. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 22 26 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. There is also strong mechanistic evidence for the facilitated development of the K65R mutation based on the viral template in the codon 64, 65 and 66 RT region found in subtype C. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 81 85 RT 150 152 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Worryingly a recent worldwide multicentre retrospective cohort study in patients with treatment failure on tenofovir and NNRTI-based regimens found the K65R prevalence to range from below 20% in Europe and North America to 50% in sub-Saharan Africa. 2017 The Journal of antimicrobial chemotherapy Introduction HIV K65R 152 156 NNRTI 121 126 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. As ABC usage in children has become more widespread, mutations, such as L74V/I, which confer resistance to the drug will become more relevant. 2017 The Pediatric infectious disease journal Introduction HIV L74I;L74V 72;72 78;78 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. However, there are limited data available on L74V/I mutations among children receiving ABC-based ART, especially when routine virologic monitoring is not available. 2017 The Pediatric infectious disease journal Introduction HIV L74I;L74V 45;45 51;51 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. Furthermore, these same DAANs also inhibited the E138K+M184I viral strain with resistance FCs ranging from 1.4 to 6.3, better than or similar to that of 2 in the same assay. 2017 Bioorganic & medicinal chemistry letters Introduction HIV E138K;M184I 49;55 54;60 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. In summary, this study revealed the following findings: (1) the R1 carbonyl conjugated with the central ring (B-ring) can be from an ester or amide for low nanomolar potency against both HIV-1 wild-type and 2-resistant (E138K, E138K+M184I) viral strains replication; (2) although compounds with ester-R1 groups exhibited slightly higher potency, amide-R1 side chains are considered superior because of improved aqueous solubility, lipophilicity, and metabolic stability; (3) short N-substituents on the amide-R1 side chain are favored for better drug-like properties. 2017 Bioorganic & medicinal chemistry letters Introduction HIV E138K;E138K;M184I 220;227;233 225;232;238 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. Next, selected highly potent compounds (EC50(wt) < 10 nM) were tested against the NL4-3 variants with E138K and double-mutated E138K+M184I drug resistant genotypes. 2017 Bioorganic & medicinal chemistry letters Introduction HIV E138K;E138K;M184I 102;127;133 107;132;138 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. Recently, our structure-activity relationship (SAR) and molecular modeling studies on a series of p-cyanoethyl-DAAN compounds revealed that the R1 substituent can also be altered to provide activity against the drug-resistant E138K variant, a major mutation conferring resistance to 2. 2017 Bioorganic & medicinal chemistry letters Introduction HIV E138K 226 231 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. Specifically, a carbonyl group in this substituent conjugated with the B-ring is likely a necessary structure for improved activity against the drug-resistant E138K variant. 2017 Bioorganic & medicinal chemistry letters Introduction HIV E138K 159 164 28465101 Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus. The new p-cyanovinyl-DAAN compounds 8a-8g, plus prior lead 3 and three related p-cyanoethyl-DAANs (4a-4c), were evaluated in parallel against wild-type and resistant viral strains E138K and E138K+M184I resistant to new-generation NNRTI drug 2. 2017 Bioorganic & medicinal chemistry letters Introduction HIV E138K;E138K;M184I 180;190;196 185;195;201 NNRTI 230 235 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Dolutegravir is far less prone to the development of resistance in first-line therapy with isolated reported cases of the emergence of R263K, N155H or G118R. 2017 The Journal of antimicrobial chemotherapy Introduction HIV G118R;N155H;R263K 151;142;135 156;147;140 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. However, the rapid acquisition of R263K or S153Y mutations with dolutegravir compromised viral replicative competence and hindered viral breakthrough. 2017 The Journal of antimicrobial chemotherapy Introduction HIV R263K;S153Y 34;43 39;48 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Resistance to elvitegravir and raltegravir occurs via several mutational pathways, including: (i) N155H or G140A/G148RHQ pathways conferring raltegravir and elvitegravir cross-resistance; (ii) T66I or E92Q/G elvitegravir-specific pathways; or (iii) the Y143R/H/C raltegravir-specific resistance pathway. 2017 The Journal of antimicrobial chemotherapy Introduction HIV E92G;E92Q;G140A;G148H;G148Q;G148R;N155H;T66I;Y143C;Y143H;Y143R 201;201;107;113;113;113;96;191;253;253;253 207;207;112;120;120;120;103;197;262;262;262 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Here, we report the differential ability of Tat variants with Ser46Phe mutation to significantly enhanced LTR transactivation (P < 0.05) compared to wild-type and other Tat variants that lack this mutation. 2017 Frontiers in microbiology Introduction HIV S46F 62 70 LTR;Tat;Tat 106;44;169 109;47;172 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. However, a novel Ser46Phe mutation is prevalent among North Indian population. 2017 Frontiers in microbiology Introduction HIV S46F 17 25 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Molecular dynamics (MDs) simulation data confirmed that Ser46Phe mutation exhibits a strong binding with TAR. 2017 Frontiers in microbiology Introduction HIV S46F 56 64 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. In a recent study on acquired ARV drug resistance mutations in treatment experienced patients in Zimbabwe, 11 of 108 (10%) patients had primary drug resistance mutations, with the mutation M184V occurring most frequently. 2017 The open microbiology journal Introduction HIV M184V 189 194 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. TAMs result in multi-nucleoside resistance, K103N and Y181C mutations cause high-level resistance to efavirenz (EFV) and nevirapine (NVP), whilst M184V causes high-level resistance to lamivudine (3TC) and rapidly emerges in patients on 3TC regimens. 2017 The open microbiology journal Introduction HIV K103N;M184V;Y181C;K103N;M184V;Y181C 45;147;55;44;146;54 50;152;60;49;151;59 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. The most commonly occurring mutations were the NNRTI mutation K103N (1.8%), thymidine analog mutation (TAM): M41L (1.6%) and NRTI mutation M184V (1.2%). 2017 The open microbiology journal Introduction HIV K103N;M184V;M41L 62;139;109 67;144;113 NNRTI;NRTI 47;125 52;129 28576126 Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee. Interestingly, this was not the case in Cotton where both M184I (ATG to ATA) and M184V (ATG to GTA) were observed at viral rebound, but M184I remained the predominant mutation. 2017 Retrovirology Introduction HIV M184I;M184I;M184V 58;136;81 63;141;86 28576126 Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee. This analysis revealed the emergence of M184V and M184I mutations in the conserved YMDD motif of the viral reverse transcriptase (RT) nine months after the onset of therapy. 2017 Retrovirology Introduction HIV M184I;M184V 50;40 55;45 RT;RT 107;130 128;132 28576126 Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee. Viruses containing the M184I (ATG to ATA) mutation usually emerge first, but are rapidly outcompeted by viruses containing the M184V (ATG to GTG) mutation due to their enhanced replication fitness. 2017 Retrovirology Introduction HIV M184I;M184V 23;127 28;132 28604824 Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. Once the M184V mutation develops, no additional mutations occur with further use of 3TC or FTC monotherapy. 2017 PloS one Introduction HIV M184V 9 14 28604824 Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. The rationale for this strategy is as follows: 1) 3TC or FTC are components of the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone of most first line cART regimens, 2) 3TC and FTC have minimal side effects, 3) the M184V resistance mutation, resulting in high-level drug resistance to both 3TC and FTC, develops rapidly in the setting of nonadherence and is present in many treatment-experienced children and adolescents with PA-HIV, 4) the M184V resistant mutation reduces viral fitness, and has been associated with a reduction in viral load of approximately 0.5 log10 c/mL, and 5) it does not confer significant cross-resistance to other NRTIs and increases susceptibility of HIV to other antiretroviral (ARV) drugs [e.g., tenofovir disproxil fumarate (TDF), zidovudine (AZT)]. 2017 PloS one Introduction HIV M184V;M184V 236;462 241;467 RT;NRTI;NRTI 105;138;662 126;142;667 28640909 HIV-Tat regulates macrophage gene expression in the context of neuroAIDS. We also demonstrated that a mutation of Tat, substitute lysine 50 for alanine, K50A, altered the expression of these genes, suggesting that lysine 50 of Tat is regulating C5, CRLF2, APBA1, and BDNF. 2017 PloS one Introduction HIV A50K;K50A 56;79 77;83 Tat;Tat 40;153 43;156 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. As rilpivirine PrEP will presumably fail to protect against infection by reverse transcriptase-E138X-containing strains, establishing their regional prevalence is paramount. 2017 AIDS (London, England) Introduction HIV E138X 95 100 RT 73 94 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. However, no previous study has characterized reverse transcriptase-E138X prevalence and its association with HLA-B*18 frequency across HIV-1 subtypes and global populations. 2017 AIDS (London, England) Introduction HIV E138X 67 72 RT 45 66 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. However, whereas HIV-1 variants resistant to tenofovir disoproxil fumarate are still relatively uncommon in most areas, and integrase-resistant variants rarer still, rilpivirine-resistant variants, in particular those with mutations at the 138th position of HIV-1 reverse transcriptase (E138X), occur naturally at a significant frequency in some areas. 2017 AIDS (London, England) Introduction HIV E138X 287 292 RT;IN 264;124 285;133 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. In light of recent studies demonstrating ongoing adaptation of HIV-1 to HLA class I, we combine in-vitro experiments with analyses of host and viral genetic data to test the hypothesis that differential global reverse transcriptase-E138X frequencies reflect the B*18-mediated selection and subsequent stable transmission of these variants in human populations, and interpret our observations in context of the regional implications for the use of rilpivirine as PrEP. 2017 AIDS (London, England) Introduction HIV E138X 232 237 RT 210 231 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Indeed, reverse transcriptase-E138X was previously shown to be significantly enriched among HIV-1 subtype B-infected individuals carrying the human leukocyte antigen (HLA) class I-B*18 allele; reverse transcriptase-E138X variants were later confirmed to be HLA-B*18-restricted CD8+ cytotoxic T-lymphocyte escape mutations occurring at the second (HLA/peptide anchor) position of a B*18-restricted cytotoxic T-lymphocyte epitope spanning HIV-1 reverse transcriptase codons 137-144. 2017 AIDS (London, England) Introduction HIV E138X;E138X 30;215 35;220 RT;RT;RT 8;193;443 29;214;464 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. Among long-term non-progressors (LTNPs), found a high frequency of the R77Q mutation, and this Vpr mutation impaired apoptosis both in vivo and in vitro. 2014 JMM case reports Introduction HIV R77Q 71 75 Vpr 95 98 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. Mutations such as R73A, R77A and R80A abolish the ability of Vpr to induce apoptosis in T-lymphocytes. 2014 JMM case reports Introduction HIV R73A;R77A;R80A 18;24;33 22;28;37 Vpr 61 64 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. The Q3R mutation occurs at the N terminus of Vpr. 2014 JMM case reports Introduction HIV Q3R 4 7 Vpr 45 48 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Certain CA point mutations, such as N74D, are independent of Nup358, Nup153, CPSF6 and TNPO3 for infection, and show a different integration site selection compared to wild type virus. 2017 PLoS pathogens Introduction HIV N74D 36 40 Capsid 8 10 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Compound libraries are screened to find selective hits that inhibit WT more than N74D. 2017 PLoS pathogens Introduction HIV N74D 81 85 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Here, using this novel screening approach, we found that the cardiac glycoside digoxin inhibits WT more potently than N74D virus. 2017 PLoS pathogens Introduction HIV N74D 118 122 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. The WT virus expresses GFP whereas N74D expresses mCherry. 2017 PLoS pathogens Introduction HIV N74D 35 39 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. To gain greater insight into these steps of the HIV-1 life cycle, we have taken advantage of the differences between wild type (WT) and N74D mutant CA to design a novel high through put screening assay whereby CD4+ T-cells are co-infected with WT and N74D single cycle HIV-1 vectors, which are identical except for the CA point mutation. 2017 PLoS pathogens Introduction HIV N74D;N74D 136;251 140;255 Capsid;Capsid 148;319 150;321 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. We found that WT virus, but not N74D virus, preferentially integrates into such genes and is affected by their repression. 2017 PLoS pathogens Introduction HIV N74D 32 36 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Here, we demonstrate that a single arginine (R) to glycine (G) mutation at position 76 in the refp17 backbone, as in S75X, is sufficient to induce dramatic changes in protein folding and stability, making p17 mutant capable of activating Akt and promoting B-cell proliferation. 2017 Scientific reports Introduction HIV S75X 117 121 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. In this study, we investigated the aa substitutions, the structural bases and the molecular mechanisms responsible for opposite effects in modulating B-cell growth between a vp17 derived from a Ugandan HIV-1 strain (subtype A1), named S75X, and the wild type p17 (reference p17, refp17; from clone BH10 of the clade B isolate). 2017 Scientific reports Introduction HIV S75X 235 239 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Specifically, V106M (NNRTI), K65R (NRTI) and N348I are more common among subtype C strains compared to other group M strains. 2017 AIDS research and therapy Introduction HIV K65R;N348I;V106M 29;45;14 33;50;19 NNRTI;NRTI 21;35 26;39 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. In particular, Arg52, Agr56, and Arg57 are critically important for transactivation (Edwards et al.,), while any changes in these mutations namely Arg52Gly, Arg56Gln, Arg57Gly, Ser62Gly, and Thr64Asp could lead to reduced TAR interaction and decreased viral transactivation (Pantano et al.,; Turk et al.,). 2017 Frontiers in microbiology Introduction HIV R52G;R56Q;R57G;S62G;T64D 147;157;167;177;191 155;165;175;185;199 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. Natural mutant Ser46Phe exhibited more hydrogen bond interactions with TAR than the wild type Tat (that lacked Ser46Phe) by molecular docking. 2017 Frontiers in microbiology Introduction HIV S46F;S46F 15;111 23;119 Tat 94 97 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Deep sequencing analyses did not detect additional resistance development but revealed key mutations at baseline, such as the polymorphic primary T97A substitution in IN. 2017 HIV clinical trials Introduction HIV T97A 146 150 IN 167 169 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. In this study, we show that amino acids Asp256, Lys260, Lys263 and Glu267 of GAPDH interact with MA and CA-NTD domain of Pr55gag and the D256R/K260E/K263E/E267R mutant of GAPDH acts as a dominant negative inhibitor of tRNALys3 packaging. 2016 Biochemistry and biophysics reports Introduction HIV D256R;E267R;K260E;K263E 137;155;143;149 142;160;148;154 Asp;Matrix;Capsid;PR 40;97;104;121 43;99;106;123 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. In this study, we found that the earliest mutation K43R in the gag gene in CH0131 was strongly selected and rapidly predominated in the viral population within 6 months of infection. 2017 Retrovirology Introduction HIV K43R 51 55 Gag 63 66 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Our findings define a new approach to study the binding properties of DTG to IN and reach deeper insight into the mechanisms of drug resistance mutations such as G187R, F190Y and S217K (equivalent to G118R, F121Y and G140S/Q148K mutations, respectively, in INHIV). 2017 Scientific reports Introduction HIV F121Y;F190Y;G118R;G140S;G187R;Q148K;S217K 207;169;200;217;162;223;179 212;174;205;222;167;228;184 IN 77 79 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Recently, we have identified and characterized two novel single mutations, G118R and F121Y, originally described in patients failing RAL-containing regimens, that also confer resistance against DTG, however, to different extents (G118R>>F121Y). 2017 Scientific reports Introduction HIV F121Y;F121Y;G118R;G118R 85;237;75;230 90;242;80;236 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Also common were associated DRMs K70E and Y115F. 2018 AIDS research and human retroviruses Introduction HIV K70E;Y115F 33;42 37;47 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. As expected, M184I/V was the most common NRTI mutation, present in 82.6% of patients at S1 and 96.8% at S2. 2018 AIDS research and human retroviruses Introduction HIV M184I;M184V 13;13 20;20 NRTI 41 45 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. As expected, patients failing AZT-based therapy did not develop mutations K65R, K70E, L74V, or Y115F, and only rarely were DRMs from the Q151M complex seen. 2018 AIDS research and human retroviruses Introduction HIV K65R;K70E;L74V;Q151M;Y115F 74;80;86;137;95 78;84;90;142;100 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Based on drug availability to the program, 3TC was prescribed more frequently in patients enrolling in the year 2008 and later, so a logistic regression model was used to determine whether year of ART start or time on treatment could explain the differences in the emergence of K65R. 2018 AIDS research and human retroviruses Introduction HIV K65R 278 282 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Based on significant previous research of DRMs, TAMs have been described to associate into one of two distinct pathways: TAM-1 (M41L, L210W, T215Y) or TAM-2 (D67N, K70R, T215F, K219E/Q). 2018 AIDS research and human retroviruses Introduction HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 158;177;177;164;134;128;170;141 162;184;184;168;139;132;175;146 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. examined 167 Indian patients with immunological failure on TDF-based 1L regimen, all with subtype C infection, and found TAMs, some coexisting with K65R. 2018 AIDS research and human retroviruses Introduction HIV K65R 148 152 HIV infections 90 109 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. For all TAMs, with the exception of K219E, D67N, and K70R, there was no acquisition from S1 to S2 in patients on TDF, whereas the mean acquisition rates of individual TAMs in the patients on AZT varied from 0.005 mutations per month to 0.019 mutations per month. 2018 AIDS research and human retroviruses Introduction HIV D67N;K219E;K70R 43;36;53 47;41;57 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. However, in the 31 patients with no K65R present at S2, 6 had intermediate or high-level resistance to AZT: 4 were caused by TAM-2 DRMs, 1 by T215Y, and 1 by Q151M-complex mutations Q151M, A62V, V75I, F77L, F116Y. 2018 AIDS research and human retroviruses Introduction HIV A62V;F116Y;F77L;K65R;Q151M;Q151M;T215Y;V75I 189;207;201;36;158;182;142;195 193;212;205;40;163;187;147;199 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. However, other groups have reported similar results: Etiebet et al., looking at Nigerian patients failing 1L regimen, found that 2 of 23 patients with TDF exposure had K219E, in a population with predominantly subtypes G and CRF02_AG. 2018 AIDS research and human retroviruses Introduction HIV K219E 168 173 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. However, three males in the study exhibited the K65R, K219E +- D67N pattern. 2018 AIDS research and human retroviruses Introduction HIV D67N;K219E;K65R 63;54;48 67;59;52 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In comparing the observed versus expected frequencies of individual mutations, K219E was 26% more likely to appear with K65R than expected in both S1 and S2 samples in patients on TDF. 2018 AIDS research and human retroviruses Introduction HIV K219E;K65R 79;120 84;124 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In conclusion, contrary to widespread thought that TAMs do not develop in the presence of K65R, our study found that nearly one-third of patients with K65R developed TAM-2s. 2018 AIDS research and human retroviruses Introduction HIV K65R;K65R 90;151 94;155 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In contrast, K219E developed significantly more quickly in patients on TDF (mean of 0.017 mutations per month) than in patients on AZT (0.006 mutations per month). 2018 AIDS research and human retroviruses Introduction HIV K219E 13 18 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In patients failing an AZT-containing regimen, TAMs were the most common DRMs after M184I/V. 2018 AIDS research and human retroviruses Introduction HIV M184I;M184V 84;84 91;91 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In patients failing TDF-based therapy, the predominant NRTI DRM aside from M184I/V was K65R, which was present in 45/87 (51.7%) S1 and 56/87 (64.4%) S2 patients. 2018 AIDS research and human retroviruses Introduction HIV K65R;M184I;M184V 87;75;75 91;82;82 NRTI 55 59 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In the 56 patients with K65R present at S2, none of the TAMs (K219E +- D67N) were predicted to cause resistance to the AZT component of a potential 2L regimen. 2018 AIDS research and human retroviruses Introduction HIV D67N;K219E;K65R 71;62;24 75;68;28 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In this population, Y181C was more common in NVP-exposed patients, whereas K103N, V108I, and P225H were more common in EFV-exposed patients (p < .001). 2018 AIDS research and human retroviruses Introduction HIV K103N;P225H;V108I;Y181C 75;93;82;20 80;98;87;25 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. In viruses lacking K65R, the TAMs observed included a broader array of primarily TAM-2, including K219E, D67N, K70R, T215F, and K219Q, and in one patient with TAM-1, T215Y. 2018 AIDS research and human retroviruses Introduction HIV D67N;K219E;K219Q;K65R;K70R;T215F;T215Y 105;98;128;19;111;117;166 109;103;133;23;115;122;171 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. It is also worth noting that in the cases of the patients harboring TAMs that coexist with K65R, the distinct patterns seen in the TDF-treated patients differ markedly from those in AZT-treated patients. 2018 AIDS research and human retroviruses Introduction HIV K65R 91 95 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. K65R emerged more often by S2 in patients on a regimen in which the 1L TDF regimen contained 3TC (16/19, 84.2%) than FTC (14/32, 43.8%) (p = .005). 2018 AIDS research and human retroviruses Introduction HIV K65R 0 4 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Our finding of a relatively high frequency of K219E in patients with K65R was surprising. 2018 AIDS research and human retroviruses Introduction HIV K219E;K65R 46;69 51;73 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Previous research has shown that TAMs and K65R rarely coexist on the same genome. 2018 AIDS research and human retroviruses Introduction HIV K65R 42 46 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. TAMs were observed in 23.8% of samples at S1 and 29.0% of samples at S2, in those without K65R. 2018 AIDS research and human retroviruses Introduction HIV K65R 90 94 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. The collection and testing of paired samples from each patient also gave us the unique opportunity to closely examine the evolution of DRMs, including thymidine analogue mutations (TAMs) and K65R. 2018 AIDS research and human retroviruses Introduction HIV K65R 191 195 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. The most common mutations detected were Y181C, K103N, G190A, A98G, K101E, V108I, H221Y, M230L, and P225H. 2018 AIDS research and human retroviruses Introduction HIV A98G;G190A;H221Y;K101E;K103N;M230L;P225H;V108I;Y181C 61;54;81;67;47;88;99;74;40 65;59;86;72;52;93;104;79;45 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. There was no significant difference in the prevalence of M184I/V at S1 or S2 between patients failing FTC or 3TC, or between patients with TDF or AZT exposure. 2018 AIDS research and human retroviruses Introduction HIV M184I;M184V 57;57 64;64 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. These findings come from a mixture of countries and subtypes, including a small number from the same clinics described in this article, so direct comparisons are not possible; however, the predominant TAMs seemed to be D67N, K219E, and M41L. 2018 AIDS research and human retroviruses Introduction HIV D67N;K219E;M41L 219;225;236 223;230;240 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. This was not true of other TAMs present in patients on 1L TDF, such as T215Y, D67N, K70R, T215F, or K219Q. 2018 AIDS research and human retroviruses Introduction HIV D67N;K219Q;K70R;T215F;T215Y 78;100;84;90;71 82;105;88;95;76 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. When controlling for both, K65R was still less likely to appear in patients on FTC than on 3TC (p = .004). 2018 AIDS research and human retroviruses Introduction HIV K65R 27 31 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. When K65R was present, the only TAMs detected were K219E +- D67N in 7/45 (15.6%) S1 samples and in 17/56 (30.4%) S2 samples. 2018 AIDS research and human retroviruses Introduction HIV D67N;K219E;K65R 60;51;5 64;56;9 29084434 Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy. Without performing single-genome sequencing, we cannot verify that these TAMs coexist on the same virus with K65R, but in terms of the potential clinical importance of the patterns, they are all present in the same patient at levels detectable by population sequencing (~20%). 2018 AIDS research and human retroviruses Introduction HIV K65R 109 113 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Clinical isolates previously obtained from the Wayne State University Infectious Disease Clinic in Detroit, MI contain major drug resistance mutations L33F, I47V, I50V, I54M, L76V, V82I/F, and I84F as well as nonpolymorphicaccessory mutations L10V/G, V11I, I13V, K20T/R, L33I/M, K43T, F53L, A71L, T74P, and L89V. 2015 Biochemistry and biophysics reports Introduction HIV A71L;F53L;I13V;I47V;I50V;I54M;I84F;K20R;K20T;K43T;L10G;L10V;L33F;L33I;L33M;L76V;L89V;T74P;V11I;V82F;V82I 291;285;257;157;163;169;193;263;263;279;243;243;151;271;271;175;307;297;251;181;181 295;289;261;161;167;173;197;269;269;283;249;249;155;277;277;179;311;301;255;187;187 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. L33F is selected for in patients on a ritonavir pharmacokinetic boosted darunavir (DRV/r) regimen, is associated with DRV/r resistance, has greatly increased in prevalence since the year 2000, and has direct influence on inhibitor-interacting residues. 2015 Biochemistry and biophysics reports Introduction HIV L33F 0 4 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. L33F was initially identified as an accessory mutation to I54L/M, V32I+I47V, and I84V/I but is now recognized as a nonpolymorphic major drug resistance mutation. 2015 Biochemistry and biophysics reports Introduction HIV I47V;I54L;I54M;I84I;I84V;V32I;L33F 71;58;58;81;81;66;0 75;64;64;87;87;70;4 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. To further investigate the role of the L33F mutation, we created a recombinant MDR769 L33F PR and performed X-ray crystallographic studies. 2015 Biochemistry and biophysics reports Introduction HIV L33F 39 43 PR 91 93 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. We hypothesize that reduced flexibility of the 30s and 80s loops due to molecular anchoring properties of L33F may contribute to drug resistance. 2015 Biochemistry and biophysics reports Introduction HIV L33F 106 110 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Resistance to NNRTIs was the most prevalent (16.9%), and our previous analysis revealed that the majority (89%) of NNRTI-resistant viruses (E138A, K103N, and V179D) for subtype A1 belonged to monophyletic clusters (local transmission networks (LTNs)). 2017 Genes Introduction HIV E138A;K103N;V179D 140;147;158 145;152;163 NNRTI;NNRTI 14;115 20;120 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Specifically, 85.7% of sequences with K103N, and 82.7% with E138A belonged to one and four LTNs, respectively, suggesting that the viruses with the most prevalent NNRTI resistance mutations spread as a result of onward transmission. 2017 Genes Introduction HIV E138A;K103N 60;38 65;43 NNRTI 163 168 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Furthermore, propagation of replication-defective, PF96-dependent MHR, and SP1 mutants generated the T8I mutation in SP1 as a second-site compensatory mutation, and the T8I variant was found to affect CA-SP1 processing. 2017 Nature communications Introduction HIV T8I;T8I 101;169 104;172 SP1;SP1;SP1;Capsid 75;117;204;201 78;120;207;203 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Here, we used an integrated approach, combining MAS NMR, solution NMR, cryo-EM, and molecular dynamics (MD) simulations to investigate how the MI BVM interferes with CA maturation, and how the T8I mutation in the SP1 region influences the structure and dynamics of the CA-SP1 maturation intermediate. 2017 Nature communications Introduction HIV T8I 193 196 SP1;SP1;Matrix;Capsid;Capsid 213;272;48;166;269 216;275;50;168;271 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In the CA-SP1(T8I) mutant, the motions in SP1 are greatly reduced and the helical content is increased. 2017 Nature communications Introduction HIV T8I 14 17 SP1;SP1;Capsid 10;42;7 13;45;9 29176596 Quenching protein dynamics interferes with HIV capsid maturation. T8I corrects assembly defects of MI-dependent MHR mutations, seemingly phenocopying the effect of MI binding by stabilizing the immature lattice. 2017 Nature communications Introduction HIV T8I 0 3 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The experimental isotropic solid-state NMR chemical shifts of tubular CA-SP1(T8I) assemblies are in excellent agreement with those calculated from MD trajectories of a CTD-SP1(T8I) hexamer. 2017 Nature communications Introduction HIV T8I;T8I 77;176 80;179 SP1;SP1;Capsid 73;172;70 76;175;72 29176596 Quenching protein dynamics interferes with HIV capsid maturation. We demonstrate by MAS NMR that the SP1 region is stabilized in a helical conformation in CA-SP1(T8I) tubular assemblies and that structural changes are induced throughout the entire CA domain. 2017 Nature communications Introduction HIV T8I 96 99 SP1;SP1;Matrix;Capsid;Capsid 35;92;18;89;182 38;95;20;91;184 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. This A316W substitution is included in the next-generation SOSIP.v4 design that we now routinely apply to new Env trimers. 2018 The Journal of biological chemistry Introduction HIV A316W 5 10 Env 110 113 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Two hydrophobic mutations in the V3 loop of BG505 SOSIP trimers, S306L and R308L, that increased the stability of BG505 SOSIP immunogens, further reduced binding of V3 non-NAbs to the trimers and severely impaired V3-directed, tier 1A NAb responses in vaccinated rabbits. 2018 The Journal of biological chemistry Introduction HIV R308L;S306L 75;65 80;70 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We previously identified a stabilizing mutation within the V3 region, A316W, that increases hydrophobic packing of the V3 loop, effectively sequestering the V3 loop in its prefusion conformation in the hydrophobic pocket underneath the V1V2 domains. 2018 The Journal of biological chemistry Introduction HIV A316W 70 75 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. The assay currently detects the most common drug resistance mutation, M184V, and can be adapted to detect other high-impact mutations. 2018 Analytical biochemistry Introduction HIV M184V 70 75 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. In addition, evidence from KwaZulu Natal found that amongst adults who had recently been diagnosed (<= 24 months), 7.1% had some form of resistant mutation, with the most common NNRTI mutation being K103N (27, 3.8%). 2017 PloS one Introduction HIV K103N 199 204 NNRTI 178 183 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. We employed glycosylation-site tetherin mutants (N65A, N92A, and N65,92A) and chemical inhibitors of the glycosylation pathway. 2018 Viruses Introduction HIV N65A;N92A 49;55 53;59 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. For instance, raltegravir resistance mutations Q148H/K/R and N155H show a high level of cross-resistance with elvitegravir, but elvitegravir susceptibility is unaffected by Y143 mutations, a difference that is beautifully explained by crystal structures of the intasome in presence of raltegravir or elvitegravir. 2018 Retrovirology Introduction HIV N155H;Q148H;Q148K;Q148R 61;47;47;47 66;56;56;56 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Resistance is commonly associated with selection of one of the signature raltegravir resistance mutations Y143C/R/H, Q148H/K/R or N155H. 2018 Retrovirology Introduction HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 130;117;117;117;106;106;106 135;126;126;126;115;115;115 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. The G140S plus Q148H combination is considered the most resistant variant and has little effect on viral replication. 2018 Retrovirology Introduction HIV G140S;Q148H 4;15 9;20 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. The resistance patterns observed in HIV-1 patients on a raltegravir containing regimen are very diverse and Q148H/K/R (usually with G140A/C/S and/or E138A/K) and N155H (often together with E92Q or V151I) mutations are observed more frequently than Y143 mutations. 2018 Retrovirology Introduction HIV E138A;E138K;E92Q;G140A;G140C;G140S;N155H;Q148H;Q148K;Q148R;V151I 149;149;189;132;132;132;162;108;108;108;197 156;156;193;141;141;141;167;117;117;117;202 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. These observations were corroborated by in vitro analysis of resistance profiles which also uncovered two atypical INSTI resistance mutations (G118R and F121Y) that confer pan-INSTI resistance. 2018 Retrovirology Introduction HIV F121Y;G118R 153;143 158;149 INSTI;INSTI 115;176 120;181 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. However, in HIV-1 RTs, antiretroviral drug resistance-associated mutations such as K65R or the combination of K65R and V75I were shown to increase fidelity of DNA-dependent DNA synthesis to levels similar to those obtained with oncoretroviral RTs. 2018 Scientific reports Introduction HIV K65R;K65R;V75I 83;110;119 87;114;123 RT;RT 18;243 21;246 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. In the present study, we have determined the intrinsic fidelity of RNA-dependent DNA synthesis of several RTs that showed diverse error rates in DNA-dependent DNA polymerization assays, ranging from around 1.4 x 10-4 in the case of HIV-1BH10 RT to 1.2 x 10-5 for MLV RT or ~6.3 x 10-6 for HIV-1 group O (ESP49 strain) RT mutants K65R (O_K65R) and K65R/V75I (O_K65R/V75I). 2018 Scientific reports Introduction HIV K65R;K65R;K65R;K65R;V75I;V75I 329;347;337;360;352;365 333;351;341;364;356;369 RT;RT;RT;RT 106;242;267;318 109;244;269;320 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. The mature PRs released from different fusion tags demonstrated distinct self-degradation properties and H69D point mutation displayed different effects on precursor autoprocessing activity when fused to different tags. 2018 PloS one Introduction HIV H69D 105 109 PR 11 14 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Furthermore, cellular ubiquitination by Vpr is also required for DDR activation: the Q65R mutant of Vpr, which cannot bind DDB1/VprBP, an adaptor protein for Cul4 E3-ligase, is defective for the G2/M checkpoint activation and cellular ubiquitination. 2018 Retrovirology Introduction HIV Q65R 85 89 Vpr;Vpr 40;100 43;103 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. A case report in an highly cART-experienced patient has shown that mutation E157Q was rapidly selected and archived in intracellular HIV DNA within a short term of eight weeks of low-level replication under a RAL-based treatment. 2018 Viruses Introduction HIV E157Q 76 81 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. A case report of a non virological response to a DTG-based regimen, in a patient infected with a E157Q-mutated virus, has been described despite adequate DTG plasma concentrations. 2018 Viruses Introduction HIV E157Q 97 102 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. A few additional VF occurred in the SAILING trial after W48 and R263K mutation was detected in one of them. 2018 Viruses Introduction HIV R263K 64 69 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. A recent Italian study carried out in vitro phenotypic assays on six clinical samples harbouring E157Q-mutated viruses including three subtype B and three CRF02_AG recombinant, showing they were all susceptible to DTG and to RAL, except one at the limit of the biological cut-off for RAL. 2018 Viruses Introduction HIV E157Q 97 102 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. A recent study of the French ANRS AC11 virology network assessed the virological outcome of 39 INI-naive patients with E157Q-mutated virus initiating an INI-based regimen. 2018 Viruses Introduction HIV E157Q 119 124 IN;IN 95;153 98;156 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. A recent study of the French ANRS AC11 virology network conducted on 8528 integrase sequences from INI-naive patients showed that the overall prevalence of E157Q polymorphism was 2.7% and its distribution among HIV-1 subtypes was 1.7%, 5.6% and 2.2% in B, CRF02_AG and others non-B subtypes, respectively. 2018 Viruses Introduction HIV E157Q 156 161 IN;IN 74;99 83;102 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. assessed susceptibility to EVG of a E157Q recombinant molecular clone showing a small reduction in EVG susceptibility with a FC of 6.3. 2018 Viruses Introduction HIV E157Q 36 41 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. assessed the impact of adding the M184I/V mutation to a R263K-mutated virus on viral replicative capacity. 2018 Viruses Introduction HIV M184I;M184V;R263K 34;34;56 41;41;61 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. E157Q emergence in integrase has also been observed in the case of VF under a RAL-based treatment in two case reports. 2018 Viruses Introduction HIV E157Q 0 5 IN 19 28 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. E157Q integrase mutation is of interest too, since it is both polymorphic, with variable prevalence in INI-naive patients depending on the viral subtype, but also selected at virological failure (VF) of a RAL-based regimen in two case reports and described in a case report of a non virological response to a DTG-based regimen. 2018 Viruses Introduction HIV E157Q 0 5 IN;IN 6;103 15;106 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. E157Q Integrase Mutation. 2018 Viruses Introduction HIV E157Q 0 5 IN 6 15 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. First In Vitro Data on R263K Mutant. 2018 Viruses Introduction HIV R263K 23 28 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. First In Vivo Data on R263K Mutation Selection. 2018 Viruses Introduction HIV R263K 22 27 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. First studies reported on the M50I integrase polymorphism, since it was selected in culture secondary to the R263K mutation. 2018 Viruses Introduction HIV M50I;R263K 30;109 34;114 IN 35 44 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Further in vitro experiments performed in this study, including biochemical cell-free assays performed with purified integrase enzyme containing R263K mutation, showed a slight decrease in 3'processing and strand transfer activities compared to the wild-type virus. 2018 Viruses Introduction HIV R263K 145 150 IN 117 126 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Furthermore, in these selection experiments, S153Y and S153T substitutions were observed in combination with R263K in one subtype B and in one subtype C virus, respectively. 2018 Viruses Introduction HIV R263K;S153T;S153Y 109;55;45 114;60;50 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Furthermore, Mark Wainberg and his team conducted several studies regarding in vitro characteristics of R263K integrase mutants. 2018 Viruses Introduction HIV R263K 104 109 IN 110 119 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Furthermore, the E157Q-R263K double-mutant also displayed enhanced DTG resistance by 10-fold compared with lower-level resistance associated with R263K mutation alone. 2018 Viruses Introduction HIV E157Q;R263K;R263K 17;23;146 22;28;151 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. However, the addition of H51Y is accompanied by dramatic decreases in both enzymatic activity and viral replication. 2018 Viruses Introduction HIV H51Y 25 29 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. However, to date, the double-mutant E157Q-R263K has not yet been described in vivo at VF of an INI-based regimen. 2018 Viruses Introduction HIV E157Q;R263K 36;42 41;47 IN 95 98 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. However, we observed a slight increase of FC to EVG at 1.9 and 2.4 in the presence of E157Q in B and CRF02_AG contexts, respectively. 2018 Viruses Introduction HIV E157Q 86 91 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In a recent study, we carried out phenotypic assays using E157Q mutant generated in the subtype B context, but also in the CRF02_AG context. 2018 Viruses Introduction HIV E157Q 58 63 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In a second study based on nine patients experiencing a VF under a RAL-based treatment, E157Q mutation was one of the four different resistance mutations profiles identified at VF. 2018 Viruses Introduction HIV E157Q 88 93 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In a study based on 92 recently diagnosed, but chronically-infected, cART-naive patients, no R263K was detected by Sanger sequencing technology and was found in two samples in minority proportion only when using ultra-deep sequencing technology. 2018 Viruses Introduction HIV R263K 93 98 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In addition, R263K site-directed mutant analyses using MT4 cells in a 5-day assay with cell tier glow readout showed a FC of 2.1, 0.8 and 10.6 for DTG, RAL and EVG, respectively. 2018 Viruses Introduction HIV R263K 13 18 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In both cases the R263K mutation was selected with a plasma viral load at failure comprised between 3 and 4 log10 c/mL. 2018 Viruses Introduction HIV R263K 18 23 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In contrast, in vitro experiments showed that, in the presence of R263K mutation, resistance selection to EVG appeared earlier than in wild-type virus. 2018 Viruses Introduction HIV R263K 66 71 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In the first report of in vitro selection under DTG pressure conducted in primary human cells, the R263K substitution in integrase was identified through culture selection after 20 weeks as a DTG resistance-associated mutation. 2018 Viruses Introduction HIV R263K 99 104 IN 121 130 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In the opposite way, in vitro the presence of the R263K delayed the emergence of RAL resistance-associated mutations, whereas the simultaneous presence of either the H51Y or E138K substitutions in combination with R263K somewhat mitigated this inhibitory effect. 2018 Viruses Introduction HIV E138K;H51Y;R263K;R263K 174;166;50;214 179;170;55;219 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In the study of Anstett et al., L74M, E92Q, T97A, E157Q and G163R resistance mutations were introduced into NL4.3 subtype B HIV-1 vectors harboring N155H and R263K in tandem. 2018 Viruses Introduction HIV E157Q;E92Q;G163R;L74M;N155H;R263K;T97A 50;38;60;32;148;158;44 55;42;65;36;153;163;48 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In the study of Quashie et al., site-directed mutagenesis analysis showed that R263K did confer very low-level resistance to DTG (Fold Change (FC) = 1.06), a slight increased for EVG (FC = 1.75) and no change for RAL (FC = 0.63). 2018 Viruses Introduction HIV R263K 79 84 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In this latter, VF occurred at week 120 with a viral load of 622 c/mL and R263K was detected added to A49G and S230R integrase mutations. 2018 Viruses Introduction HIV A49G;R263K;S230R 102;74;111 106;79;116 IN 117 126 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In this manuscript, we have reviewed main in vivo and in vitro knowledge about two integrase resistance-associated mutations: R263K and E157Q. 2018 Viruses Introduction HIV E157Q;R263K 136;126 141;131 IN 83 92 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In this study, the E157Q site-directed mutants did not show an increased phenotypic resistance level to DTG or RAL both in B and CRF02_AG subtypes contexts. 2018 Viruses Introduction HIV E157Q 19 24 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In Vitro Characterization of R263K Mutants. 2018 Viruses Introduction HIV R263K 29 34 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In vitro characterization of the E157Q-mutated virus issued from this clinical sample has shown that integrase strand-transfer activity was 3-fold greater compared to wild-type virus and that IC50 value was increased, leading to a FC equal to 9. 2018 Viruses Introduction HIV E157Q 33 38 IN 101 110 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. In Vivo Selection of E157Q Mutation at Virological Failure. 2018 Viruses Introduction HIV E157Q 21 26 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Integrase E157Q substitution has been described as a polymorphism present in 2.4% of viral sequences obtained from cART-naive patients in the ARCA Italian database and in 5.0% in the last French transmitted drug resistance survey study. 2018 Viruses Introduction HIV E157Q 10 15 IN 0 9 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Interestingly, E157Q mutation is able to partially restore decrease in integrase enzymatic activity caused by the R263K substitution, thereby acting as a possible secondary, compensatory mutation. 2018 Viruses Introduction HIV E157Q;R263K 15;114 20;119 IN 71 80 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Interestingly, regarding both INI currently under development, BIC and CAB, they remained active against R263K-M50I and R263K-E138K double-mutants with less than <=4-fold increase in phenotypic resistance level. 2018 Viruses Introduction HIV E138K;M50I;R263K;R263K 126;111;105;120 131;115;110;125 IN 30 33 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. It has been shown that R263K mutants display a low viral replicative capacity. 2018 Viruses Introduction HIV R263K 23 28 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. More recently, it has been shown that in both single and multiple rounds of HIV-1 infections, bictegravir (BIC) and cabotegravir (CAB), two INIs currently under development, remained active against R263K mutant. 2018 Viruses Introduction HIV R263K 198 203 IN 140 144 HIV infections 76 92 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. One virus displayed R263K as a single mutation and phenotypic analysis of this clinical isolate showed a FC to DTG and RAL of 1.12 and 0.96, respectively, with a reduced viral replicative capacity equal to 33%. 2018 Viruses Introduction HIV R263K 20 25 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Phenotypic Analysis of E157Q Mutants. 2018 Viruses Introduction HIV E157Q 23 28 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Prevalence of E157Q in cART-Naive Patients. 2018 Viruses Introduction HIV E157Q 14 19 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Prevalence of R263K among cART-Naive Patients. 2018 Viruses Introduction HIV R263K 14 19 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. R263K and HIV Viral Subtype. 2018 Viruses Introduction HIV R263K 0 5 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. R263K and Potential Compensatory Mutations. 2018 Viruses Introduction HIV R263K 0 5 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. R263K Integrase Mutation. 2018 Viruses Introduction HIV R263K 0 5 IN 6 15 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. R263K mutation is interesting because this mutation was selected in vivo at failure of a DTG-based regimen and only displayed a moderate increase in phenotypic resistance level. 2018 Viruses Introduction HIV R263K 0 5 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Regarding its prevalence, R263K mutation is very rare in cART-naive patients, in the French epidemiological transmitted drug resistance survey conducted in patients in primary infection with a prevalence of 0.9% (n = 2/233 patients). 2018 Viruses Introduction HIV R263K 26 31 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Selection of R263K Mutation and What Behind: In Vitro Data. 2018 Viruses Introduction HIV R263K 13 18 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. showed that the presence of R263K mutation did confer a decreased integration in cell culture without altering reverse transcription step. 2018 Viruses Introduction HIV R263K 28 33 RT 111 132 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. showed that the T66I substitution emerged from a wild-type virus but also from a R263K mutant and from a E138K-R263K double-mutant virus under RAL or EVG pressure. 2018 Viruses Introduction HIV E138K;R263K;R263K;T66I 105;81;111;16 110;86;116;20 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Similarly, H51Y integrase mutation also emerged secondary to R263K mutation in DTG selection experiments. 2018 Viruses Introduction HIV H51Y;R263K 11;61 15;66 IN 16 25 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. So, in vitro characteristics of H51Y single- and H51Y-R263K double-mutants were studied showing that the addition of H51Y to R263K increased phenotypic resistance level to DTG with a FC of 16.5, whereas H51Y alone did not confer resistance to this drug. 2018 Viruses Introduction HIV H51Y;H51Y;H51Y;H51Y;R263K;R263K 32;49;117;203;54;125 36;53;121;207;59;130 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. So, the H51Y mutation is also not a compensatory mutation to the R263K. 2018 Viruses Introduction HIV H51Y;R263K 8;65 12;70 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Structural modeling suggested that the R263K mutation affects integrase-DNA interactions and in vitro integrase-DNA binding assays confirmed these data (Figure 1). 2018 Viruses Introduction HIV R263K 39 44 IN;IN 62;102 71;111 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The addition of the E138K substitution to the T66I-R263K double-mutant partially compensated for these deficits and resulted in a high level of resistance against EVG but not against DTG or RAL. 2018 Viruses Introduction HIV E138K;R263K;T66I 20;51;46 25;56;50 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The aim of this study was to assess the effects of the T66I and E138K substitutions, alone and in combination with R263K, on viral replicative capacity and resistance to INI. 2018 Viruses Introduction HIV E138K;R263K;T66I 64;115;55 69;120;59 IN 170 173 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The findings showed that M50I polymorphism in combination with R263K increased resistance to DTG in tissue culture and in biochemical assays but did not restore viral replicative capacity of the R263K mutant. 2018 Viruses Introduction HIV M50I;R263K;R263K 25;63;195 29;68;200 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The N155H is one of the major resistance pathway to the first-generation INI, and is often associated with secondary resistance mutations. 2018 Viruses Introduction HIV N155H 4 9 IN 73 76 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The presence of R263K decreased HIV-1 subtype C infectiousness by 70% compared to wild-type, whereas R263K in subtype B only resulted in a 40% decrease. 2018 Viruses Introduction HIV R263K;R263K 16;101 21;106 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The R263K substitution was reported at VF in a subtype C-infected participant in the SAILING clinical trial. 2018 Viruses Introduction HIV R263K 4 9 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The second virus harbored the V260I mutation added to the R263K, this double-mutant resulted in a FC to DTG and RAL of 1.93 and 1.12, respectively. 2018 Viruses Introduction HIV R263K;V260I 58;30 63;35 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. The single mutant V260I did not confer DTG or RAL FC increase. 2018 Viruses Introduction HIV V260I 18 23 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Their results showed that the presence of M184I or M184V with R263K further decreased viral infectiousness and replicative capacity compared to the effects of the individual mutations alone. 2018 Viruses Introduction HIV M184I;M184V;R263K 42;51;62 47;56;67 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. They found that the addition of T97A, E157Q or G163R mutation somewhat improved the affinity of the double-mutant N155H-R263K for its target DNA substrate, while the presence of L74M or E92Q had a negative effect on this step. 2018 Viruses Introduction HIV E157Q;E92Q;G163R;L74M;N155H;R263K;T97A 38;186;47;178;114;120;32 43;190;52;182;119;125;36 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. They showed that the addition of R263K to the T66I substitution did not significantly compromise susceptibility to DTG, while decreasing both viral replicative capacity and strand-transfer activity. 2018 Viruses Introduction HIV R263K;T66I 33;46 38;50 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. They showed that the presence of the E92Q or N155H resistance mutations was compatible with the emergence of R263K, whereas no R263K selection was observed in presence of G140S-Q148R, E92Q-N155H, G140S, Y143R and Q148R resistance mutations. 2018 Viruses Introduction HIV E92Q;E92Q;G140S;G140S;N155H;N155H;Q148R;Q148R;R263K;R263K;Y143R 37;184;171;196;45;189;177;213;109;127;203 41;188;176;201;50;194;182;218;114;132;208 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. This could participate to the drastic reduction of the viral replicative capacity observed in case of the presence of the R263K mutation. 2018 Viruses Introduction HIV R263K 122 127 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. This work showed that the compensatory mutations, that evolve after N155H selection under continued DTG or RAL/EVG pressure, are unable to improve enzyme efficiency, resistance level or viral infectivity in an N155H-R263K background. 2018 Viruses Introduction HIV N155H;N155H;R263K 68;210;216 73;215;221 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Thus, E157Q polymorphism does not seem to impact phenotypic susceptibility to RAL or DTG, in contrast a potential low-level resistance, especially in the context of CRF02_AG recombinant, was observed for EVG. 2018 Viruses Introduction HIV E157Q 6 11 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Thus, in vitro characteristics of a R263K site-directed mutant in the subtype C context was assessed showing a significant decrease in strand-transfer activity for the R263K integrase protein to a greater extent than observed in subtype B. 2018 Viruses Introduction HIV R263K;R263K 36;168 41;173 IN 174 183 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Thus, prolonged infections with R263K mutants led to a progressive decline in integrated HIV-1 DNA over time. 2018 Viruses Introduction HIV R263K 32 37 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Thus, some genotypic resistance profiles seem to prevent emergence of the R263K DTG resistance-associated mutation. 2018 Viruses Introduction HIV R263K 74 79 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Thus, taking into account all the data, in case of E157Q polymorphism, the most recommended INI might be DTG in such patients; EVG should not be considered due to potential low-level resistance, especially in the context of CRF02_AG recombinant and RAL seems adequate with unmounted IC50 but with the caveat that selection of E157Q has been described at VF in two case reports. 2018 Viruses Introduction HIV E157Q;E157Q 51;326 56;331 IN 92 95 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. Thus, the R263K substitution appears to be more deleterious in subtype C than in subtype B. 2018 Viruses Introduction HIV R263K 10 15 29346270 Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations. To date, very few data are available regarding virological response of patients displaying E157Q-mutated virus, only represented by case reports that limit their interpretation. 2018 Viruses Introduction HIV E157Q 91 96 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Based on the structures of RTQ151M together with the results of the antiviral assay, possible mechanisms of ETV-TP action on HIV-1/HBV RT and of the reported ETV resistance are discussed. 2018 Scientific reports Introduction HIV Q151M 29 34 RT;RT 27;135 29;137 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. In this study, we showed that the Q151M mutation of HIV-1 RT confers high ETV and EFdA sensitivity upon HIV-1. 2018 Scientific reports Introduction HIV Q151M 34 39 RT 58 60 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Notably, HIV-1 RT Q151M is a critical mutation that confers multi-NRTI resistance, accompanied by A62V, V75I, F77L, and F116Y mutations (Q151M-complex). 2018 Scientific reports Introduction HIV F116Y;F77L;Q151M;Q151M 120;110;18;137 125;114;23;142 NRTI;RT 66;15 70;17 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Recently, the structures of HIV-1 RTQ151M and RTQ151M-complex have been reported and suggest that Q151M leads to conformational perturbation of the HIV-1 RT N-site. 2018 Scientific reports Introduction HIV Q151M;Q151M;Q151M 36;48;98 41;53;103 RT;RT;RT 34;46;154 36;48;156 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The HIV-1 RTQ151M further enabled crystal structure analysis of HIV-1 RT in complex with ETV-TP. 2018 Scientific reports Introduction HIV Q151M 12 17 RT;RT 10;70 12;72 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. In two other patients, both of whom received darunavir monotherapy and had no prior PI exposure, L90M was the sole protease mutation detected; this is rarely selected de novo by darunavir and is a relatively common transmitted mutation. 2018 Journal of clinical virology Introduction HIV L90M 97 101 PR;PI 115;84 123;86 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. It appears therefore that only a single PI monotherapy patient (described below, patient A) experienced a loss of drug options due to a mutation (I50L) selected by study drug. 2018 Journal of clinical virology Introduction HIV I50L 146 150 PI 40 42 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The most DRV-resistant isolate, HIV-1DRVRP51, had acquired four major amino acid substitutions in its protease (V32I, L33F, I54M, and I84V), which have been shown to be responsible for the DRV resistance of HIV-1DRVRP51. 2018 mBio Introduction HIV I54M;I84V;L33F;V32I 124;134;118;112 128;138;122;116 PR 102 110 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The present data not only explain the mechanisms of DRV's high genetic barrier well but also suggest that the initiation or continuation of DRV-containing regimens in individuals harboring HIV-1 variants with a V32I substitution must be carefully considered and monitored. 2018 mBio Introduction HIV V32I 211 215 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We demonstrate that one of the four critical amino acid substitutions, V32I, serves as a key substitution, which rarely occurs in in vitro selection attempts, but once it occurs, it predisposes HIV-1 to develop high-level DRV resistance. 2018 mBio Introduction HIV V32I 71 75 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. For example, in an RT-SHIV-infected macaque intravenously administered TMC278LA, the RPV-associated mutation E138Q was selected 17 weeks after the second TMC278 injection and conferred low level (4-fold) RPV resistance. 2018 Antiviral chemistry & chemotherapy Introduction HIV E138Q 109 114 RT 19 21 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. HIV-1LAI with different, single NNRTI mutants maintained susceptibility to RPV, except for HIV-1 with Y181I and the double mutant K101P/V179I. 2018 Antiviral chemistry & chemotherapy Introduction HIV K101P;V179I;Y181I 130;136;102 135;141;107 NNRTI 32 37 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. In vitro analyses of NNRTI resistance mutations in both subtype B and C HIV-1 laboratory variants showed that >20-fold resistance to RPV was achieved by the NNRTI mutations Y181I/V and/or K101P. 2018 Antiviral chemistry & chemotherapy Introduction HIV K101P;Y181I;Y181V 188;173;173 193;180;180 NNRTI;NNRTI 21;157 26;162 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. This was low enough to allow breakthrough infection of wild-type virus but high enough to subsequently select NNRTI resistance with K101E. 2018 Antiviral chemistry & chemotherapy Introduction HIV K101E 132 137 NNRTI 110 115 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Domain mapping revealed that the thumb and connection domains of HIV-1 RT are important for binding to eEF1A, and mutagenesis of the RT thumb domain showed that the W252A and L303A mutations significantly impair binding to eEF1A. 2018 mBio Introduction HIV L303A;W252A 175;165 180;170 RT;RT 71;133 73;135 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Among these mutations, E138K in RT is not only the most common NNRTI resistance associated mutation found in patients who failed RPV-containing regimens but also the earliest mutation for ETR resistance in all subtypes in vitro. 2018 European journal of medicinal chemistry Introduction HIV E138K 23 28 NNRTI;RT 63;32 68;34 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Besides, E138K mutation also confers phenotypic resistance to Nevirapine (NVP) and Efavirenz (EFV). 2018 European journal of medicinal chemistry Introduction HIV E138K 9 14 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Therefore, the broad cross-resistance against nearly all of the approved NNRTIs make the development of E138K must be avoided whenever possible. 2018 European journal of medicinal chemistry Introduction HIV E138K 104 109 NNRTI 73 79 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Thus, we designed a novel series of nicotinamide derivatives based on the L-6b11 template which is the best compound from our last series, hoping to acquire better potency especially against the E138K strain. 2018 European journal of medicinal chemistry Introduction HIV E138K 195 200 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. (1991) compared PR1 structures with PR2 models and found that the differences in PR1 and PR2 affinity for two PIs were due in part to a V32I substitution. 2018 Scientific reports Introduction HIV V32I 136 140 PR;PR;PR;PR;PI 36;89;16;81;110 39;92;19;84;113 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. (2012) compared PR1 mutants containing these three mutations (V32I, I47V, and V82I) with PR1 and PR2 wild-type structures in terms of global biochemical properties and their interactions with APV. 2018 Scientific reports Introduction HIV I47V;V32I;V82I 68;62;78 72;66;82 PR;PR;PR 97;16;89 100;19;92 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. (2016), who reported the opposite observation by incorporating four HIV-1-like mutations, I32V, V47I, L76M, and I82V, into a wild-type PR2. 2018 Scientific reports Introduction HIV I32V;I82V;L76M;V47I 90;112;102;96 94;116;106;100 PR 135 138 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Several studies have focused on the link between the differences of PR1 and PR2 affinity and certain amino acid changes (V32I, M46I, I47V, L76M, and V82I) between PR1 and PR2 binding sites. 2018 Scientific reports Introduction HIV I47V;L76M;M46I;V32I;V82I 133;139;127;121;149 137;143;131;125;153 PR;PR;PR;PR 76;171;68;163 79;174;71;166 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. The structural comparison of PR1 mutants and PR1 and PR2 wild-type structures suggested a cooperative movement induced by the substitutions V32I and L76M, which induces the structural change observed at residue 45_B in PR2. 2018 Scientific reports Introduction HIV L76M;V32I 149;140 153;144 PR;PR;PR;PR 53;219;29;45 56;222;32;48 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. We speculated that the particular conformation of residue 45_B in PR2 and the substitutions M46I and I47V could modify the flexibility of PR2, impacting PI binding. 2018 Scientific reports Introduction HIV I47V;M46I 101;92 105;96 PR;PR;PI 66;138;153 69;141;155 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. However, a relatively high prevalence of Q151M has been observed in more recent studies of patients failing ART from LMICs (ranging 2-14% in these studies). 2018 AIDS research and therapy Introduction HIV Q151M 41 46 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Likewise the Q151M mutation causes intermediate/high-level resistance to zidovudine (ZDV), didanosine (DDI), stavudine (D4T), and abacavir (ABC) and low level resistance to tenofovir (TDF), lamivudine (3TC) and emtricitabine (FTC). 2018 AIDS research and therapy Introduction HIV Q151M 13 18 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. The T69i mutation has been linked to DDI use whilst for Q151M an association with D4T has been observed, and most reports of the mutations occurring in Europe date to 10 or more years ago when the use of these drugs was still widespread. 2018 AIDS research and therapy Introduction HIV Q151M 56 61 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. This paper reports changes in the prevalence of multi-drug resistance mutations Q151M and T69i in the UK-HDRD over time and evaluates outcomes in affected patients. 2018 AIDS research and therapy Introduction HIV Q151M 80 85 29683856 Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination. In that case, if the patient was not fully adherent to PrEP when exposed to HIV in the past, the patient could have developed the NRTI-resistant mutations (M184V, K70T, and K65R) through the selective pressure of FTC/TDF prophylaxis after acquiring a virus carrying the K103N mutation. 2018 AIDS (London, England) Introduction HIV K103N;K65R;K70T;M184V 270;173;163;156 275;177;167;161 NRTI 130 134 29683856 Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination. On day 2, his HIV-1 RNA was 27 316 copies/ml, and genotyping (by population sequencing) subsequently revealed significant mutations in the reverse transcriptase gene, including M184V [which reduces susceptibility to lamivudine (3TC) / emtricitabine (FTC)], K65R (which reduces susceptibility to TDF), K70T (which reduces susceptibility to TDF and FTC/3TC), and the K103N mutation (which reduces susceptibility to efavirenz and nevirapine). 2018 AIDS (London, England) Introduction HIV K103N;K65R;K70T;M184V 365;257;301;177 370;261;305;182 RT 139 160 29683856 Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination. The NRTI-resistance mutations, with their negative impact on viral fitness, are less commonly transmitted than the K103N mutation. 2018 AIDS (London, England) Introduction HIV K103N 115 120 NRTI 4 8 29683856 Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination. The reverse transcriptase gene also harbored two polymorphisms (V90I and V179I), and there were no mutations in the protease-encoding gene. 2018 AIDS (London, England) Introduction HIV V179I;V90I 73;64 78;69 RT;PR 4;116 25;124 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. A similar finding was observed in Croatia, which borders Slovenia, where a TDR prevalence of an alarming 22% was assessed, primarily due to the onward transmission of T215S revertant mutation. 2018 PloS one Introduction HIV T215S 167 172 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. It has been postulated that if these levels continue to increase, it could compromise the effectiveness of some therapeutic regimens, and since transmitted non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, especially K103N/S, can persist for years in the absence of drug selection pressure, these NNRTI mutations are of special concern. 2018 AIDS research and human retroviruses Introduction HIV K103N;K103S 233;233 240;240 NNRTI;NNRTI;NNRTI 156;204;313 192;209;318 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Analysis of Tat binding to cyclin T1 showed decreased binding of all mutants and Tat S16D and Tat S46D were having the strongest effect. 2018 Retrovirology Introduction HIV S16D;S46D 85;98 89;102 Tat;Tat;Tat 12;81;94 15;84;97 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Co-expression of Flag-tagged Tat S16A or Tat S46A mutants failed to activate integrated HIV-1 provirus with defective Tat. 2018 Retrovirology Introduction HIV S16A;S46A 33;45 37;49 Tat;Tat;Tat 29;41;118 32;44;121 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Phosphorylation of Tat by PKR enhanced Tat binding to TAR RNA and alanine mutations in Ser-62, Thr-64 and Ser-68 reduced Tat-mediated HIV-1 transcription activation. 2018 Retrovirology Introduction HIV A62S 66 93 Tat;Tat;Tat 19;39;121 22;42;124 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. TAR RNA binding was analyzed and found to be only affected by Tat S16A mutation. 2018 Retrovirology Introduction HIV S16A 66 70 Tat 62 65 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. To analyze functional consequences of Ser-16 and Ser-46 phosphorylation, we analyzed transcriptional activity of HIV-1 proviral DNA containing Ser-16 and Ser-46 alanine and phosphorylation-mimicking glutamic acid mutations which showed complete inhibition of transcription by alanine mutations and partial restoration of transcription by S16E mutation and poor restoration by S46E mutation. 2018 Retrovirology Introduction HIV S16E;S46A;S46E 338;154;376 342;168;380 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. We also analyzed nuclear localization of Tat using EGFP-fused alanine and glutamic acid mutants of Ser-16 and Ser-46, which showed deficiency in nuclear localization for Tat S46E. 2018 Retrovirology Introduction HIV S46E 174 178 Tat;Tat 41;170 44;173 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. We also assembled pseudotyped viruses from mutant pNL4-3 Luc vectors that showed partial and weak compensation by Tat S16E and Tat S46E mutations, respectively. 2018 Retrovirology Introduction HIV S16E;S46E 118;131 122;135 Tat;Tat 114;127 117;130 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. We were not able to assemble proviruses with Tat S16A or Tat S46A mutations. 2018 Retrovirology Introduction HIV S16A;S46A 49;61 53;65 Tat;Tat 45;57 48;60 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. INSTIs resistance mutations in IN sequences were interpreted using the Stanford HIVdb Program (Version September 23,2016) and screened for the presence of additional changes in 17 positions (V72I, T112I, S119PRTG, T124A, T125K, A128T, Q146K, M154I, K156N, V165I, V201I, I203M,T206S, S230N, D232N, V249I and C280Y) previously related to INIs resistance in vitro and frequently reported by different studies. 2018 BMC research notes Introduction HIV A128T;C280Y;D232N;I203M;K156N;M154I;Q146K;S119G;S119P;S230N;T112I;T124A;T125K;T206S;V165I;V201I;V249I;V72I 228;307;290;270;249;242;235;204;204;283;197;214;221;276;256;263;297;191 233;312;295;275;254;247;240;212;212;288;202;219;226;281;261;268;302;195 INSTI;IN;IN 0;336;31 6;340;33 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. Moreover, there were three amino acid substitutions of unknown significance at position 163 that were encountered in subtype B and CRF02-A/G strains: G163E, G163T and G163Q. 2018 BMC research notes Introduction HIV G163E;G163Q;G163T 150;167;157 155;172;162 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. None of the primary amino acid mutations in IN positions 66, 92, 140, 143, 147, 148 and 155 listed in the Stanford resistance algorithm were found in this study, while secondary mutations L74IM and T97A associated with drug resistance to RAL and EVG were observed only in four patients (5.2%) (Additional file 1). 2018 BMC research notes Introduction HIV L74I;L74M;T97A 188;188;198 193;193;202 IN 44 46 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. Other mutations in IN positions not included in Stanford list but frequently reported in regards to INIs resistance in vitro V72I, T112I, S119PRT, T124A, K156N, V165I, V201I, I203M,T206S and S230N have been detected with different frequencies. 2018 BMC research notes Introduction HIV I203M;K156N;S119P;S230N;T112I;T124A;T206S;V165I;V201I;V72I 175;154;138;191;131;147;181;161;168;125 180;159;145;196;136;152;186;166;173;129 IN;IN 100;19 104;21 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. Regarding DTG R263K resistance mutation, no strain from our study exhibited this mutation, whereas the L101I and T124A mutations were found in 26 and 12 strains, respectively. 2018 BMC research notes Introduction HIV L101I;R263K;T124A 103;14;113 108;19;118 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. The L74I was observed in two strains, a subtype B (KU609297) and a subtype A (KU609282). 2018 BMC research notes Introduction HIV L74I 4 8 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. The L74M was observed in one subtype B strain (KU609337) and T97A was observed in one CRF02_AG strain (KU609303). 2018 BMC research notes Introduction HIV L74M;T97A 4;61 8;65 29884219 Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. The substitutions detected in more than 95% of samples were D10E, G123S, R127K and N232D, none of which is ascribed to INI resistance. 2018 BMC research notes Introduction HIV D10E;G123S;N232D;R127K 60;66;83;73 64;71;88;78 IN 119 122 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. For instance, a transmitted M184V mutation can quickly revert to wild-type due to diminished viral fitness. 2018 African journal of laboratory medicine Introduction HIV M184V 28 33 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The most common non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were K103N (58.1%), Y181C (41.9%) and G190A (6.5%), and the most frequent nucleoside reverse transcriptase inhibitor (NRTI) mutation was M184V (61.3%). 2018 African journal of laboratory medicine Introduction HIV G190A;K103N;M184V;Y181C 119;86;218;101 124;91;223;106 NNRTI;NRTI;NNRTI;NRTI 16;155;64;199 52;187;69;203 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Interestingly, the ANRS12286/MOBIDIP trial showed the superiority of DT with lamivudine plus bPI as compared with bPI monotherapy in a population of patients virologically suppressed on a second-line regimen of 2NRTI plus bPI, carrying the M184V mutation in many cases. 2018 Open forum infectious diseases Introduction HIV M184V 240 245 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Previous selection of M184V may impact clinical decisions to implement lamivudine-containing DT, yet a direct comparison of efficacy in patients harboring or not harboring the M184V mutation has not been performed. 2018 Open forum infectious diseases Introduction HIV M184V;M184V 22;176 27;181 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The M184V mutation is associated with high-level in vitro resistance to lamivudine but also with reduced viral replication capacity. 2018 Open forum infectious diseases Introduction HIV M184V 4 9 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. This study aimed at comparing the virological efficacy of lamivudine-based maintenance DT in clinical practice patients with suppressed viral load, with (M184V+) or without (M184V-) a history of M184V detection. 2018 Open forum infectious diseases Introduction HIV M184V;M184V;M184V 154;174;195 160;179;200 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. An initial study reported that the A62V mutation alone increases HIV-1 mutant frequencies, and causes a minor decrease in virus fitness. 2018 Viruses Introduction HIV A62V 35 39 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. HIV-1 reverse transcriptase (RT), which is the enzyme responsible for converting the single-stranded viral RNA genome into double-stranded DNA, was previously observed to acquire the A62V amino acid substitution, which is known to be associated with multi-drug resistance but is not a resistance-conferring mutation. 2018 Viruses Introduction HIV A62V 183 187 RT;RT 6;29 27;31 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In particular, A62V is normally seen in different mutational arrangements, located mostly on the flexible beta3-beta4 loop region of the fingers sub-domain of HIV-1 RT, including the multi-dideoxynucleoside resistant (MDR) Q151M complex (i.e., A62V, V75I, F77L, F116Y, and Q151M) and the T69SSS insertion complex, which has a serine-serine insertion between the amino acid positions 69 and 70 (i.e., M41L, A62V, T69SSS, K70R, and T215Y). 2018 Viruses Introduction HIV A62V;A62V;A62V;F116Y;F77L;K70R;M41L;Q151M;Q151M;T215Y;T69SSS;T69SSS;V75I 15;244;406;262;256;420;400;221;273;430;288;412;250 19;248;410;267;260;424;404;228;278;435;294;418;254 RT 165 167 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In this study, we sought to determine the role of A62V in HIV-1 viral mutagenesis and fitness in the context of clinically relevant drug-resistant mutations. 2018 Viruses Introduction HIV A62V 50 54 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Notably, the inclusion of A62V in the context of various MDR mutation complexes improved viral fitness in the presence of AZT. 2018 Viruses Introduction HIV A62V 26 30 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The inclusion of the A62V substitution increased the observed lower mutant frequencies with each of the HIV-1 MDR complex mutants. 2018 Viruses Introduction HIV A62V 21 25 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The Q151M complex and the T69SSS insertion complex confer resistance to most of the NRTIs currently used for treatment including didanosine, zalcitabine, stavudine, and zidovudine (AZT), while the Q151M complex additionally confers resistance to lamivudine and abacavir. 2018 Viruses Introduction HIV Q151M;Q151M;T69SSS 4;197;26 9;202;32 NRTI 84 89 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. These observations together implicate an adaptive role for A62V in enhancing virus persistence during drug-selective pressure. 2018 Viruses Introduction HIV A62V 59 63 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. To do this, we first used a single-cycle assay to assess the mutant frequency of the HIV-1 MDR complex mutants (i.e., the Q151M complex and the T69SSS insertion complex) in the presence or absence of the A62V substitution. 2018 Viruses Introduction HIV A62V;Q151M;T69SSS 204;122;144 208;127;150 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. First, we performed a proline substitution screen across the gp41 HR1 region identifying a new proline substitution (L555P) that improves the generation of stable trimers in some contexts. 2018 Frontiers in immunology Introduction HIV L555P 117 122 gp41 61 65 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Second, using structure-guided design, we screened 15 cysteine pairs at different positions, identifying a new cysteine pair A501C-L663C ("CC2") that forms a stabilizing inter-protomer disulfide bond that is compatible with most TD CC+ substitutions. 2018 Frontiers in immunology Introduction HIV A501C;L663C 125;131 130;136 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The original NFL trimer design contains the I559P mutation as well to disfavor the post-fusion state. 2018 Frontiers in immunology Introduction HIV I559P 44 49 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The SOSIPs are proteolytically cleaved by cellular furins to gp120 and gp41 subunits, covalently linked by an engineered intra-protomer disulfide bond A501C-T605C (SOS). 2018 Frontiers in immunology Introduction HIV A501C;T605C 151;157 156;162 gp120;gp41 61;71 66;75 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. These trimers also contain a I559P substitution in the gp41 heptad repeat 1 (HR1) region to generate well-ordered oligomers and, as well, require expression of exogenous furin for conformational integrity. 2018 Frontiers in immunology Introduction HIV I559P 29 34 gp41 55 59 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. This design uses a flexible linker (two copies of Gly4-Ser, "G4S") to replace the natural cleavage site. 2018 Frontiers in immunology Introduction HIV G4S;G4S 61;50 64;58 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. BIC and DTG showed high barriers to in vitro resistance in MT-2 cells, with emergent M50I and R263K conferring low-fold resistance in the nM range. 2018 Retrovirology Introduction HIV M50I;R263K 85;94 89;99 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Drug resistance is associated with the accumulation of primary resistance substitutions and relevant compensatory substitutions along several pathways including the (1) N155H and G140A/G148R/H/Q pathways conferring high level cross-resistance to RAL and EVG; (2) the T66I or E92Q/G pathways leading to resistance to EVG; or (3) the Y143R/H/C RAL-specific resistance pathway. 2018 Retrovirology Introduction HIV G140A;G148H;G148Q;G148R;E92G;E92Q;T66I;Y143C;Y143H;Y143R 179;185;185;185;275;275;267;332;332;332 184;194;194;194;281;281;271;341;341;341 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In addition, recombinant strains of HIV-1 with integrase derived from clinical isolates assessed the impact of E157Q substitution on emergent resistance to relevant INSTIs was assessed at weeks 8, 16, 24 and 46. 2018 Retrovirology Introduction HIV E157Q 111 116 IN;INSTI 47;165 56;171 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In cell culture selections with DTG, the emergence of singleton R263K, S153Y or H51Y mutations confers low-level resistance (< 3-fold resistance) and contributes to a significant negative impact on viral replicative fitness. 2018 Retrovirology Introduction HIV H51Y;R263K;S153Y 80;64;71 84;69;76 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Interestingly, R263K-containing viruses do not seem able to acquire compensatory substitutions that might increase levels of resistance. 2018 Retrovirology Introduction HIV R263K 15 20 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. One patient acquired virus with the Q148R mutation, conferring phenotypic resistance to RAL, EVG and CAB, in association with the K103N, E138G, and K238T, conferring cross-resistance to non-nucleoside RT inhibitors (NNRTIs). 2018 Retrovirology Introduction HIV E138G;K103N;K238T;Q148R 137;130;148;36 142;135;153;41 NNRTI;RT 216;201 222;203 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Similarly, at week 48 in the Phase 2 Latte study, the injectable long-acting formulation of CAB and RIL was non-inferior to efavirenz on a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone with one virological failure in injectable CAB/RIL arm harbouring viruses acquiring the INSTI-associated Q148R mutation with the E138Q NNRTI-resistant mutation. 2018 Retrovirology Introduction HIV E138Q;Q148R 332;308 337;313 NRTI;INSTI;NNRTI;NRTI 144;291;338;188 176;296;343;192 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Two of these individuals acquired the R263K mutation that had previously been selected in culture by DTG to confer low-level resistance. 2018 Retrovirology Introduction HIV R263K 38 43 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Moreover, we found that nine amino acid substitutions, namely, M41L, D67Delta, T69G, K70R, L74I, V75T, M184V, T215F, and K219Q (in HIV-1EFdAR), were associated with EFdA resistance. 2018 Cell chemical biology Introduction HIV K219Q;K70R;L74I;M184V;M41L;T215F;T69G;V75T 121;85;91;103;63;110;79;97 126;89;95;108;67;115;83;101 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. reported that a moderate resistance of HIV-1 against EFdA (22-fold change compared with that against wild-type HIV-1 [HIV-1WT]) was associated with three amino acid substitutions (I142V, T165R, and M184V) in the RT-encoding gene. 2018 Cell chemical biology Introduction HIV I142V;M184V;T165R 180;198;187 185;203;192 RT 212 214 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Only Y135F mutation within NefYF9 out of the 4 epitopes, which selected by HLA-A*24:02-restircted T cells, impaired an ability of YF9-specific T cells to suppress HIV-1 replication in vivo and in vitro. 2018 EBioMedicine Introduction HIV Y135F 5 10 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Clinical inhibitor 2 was selected because L76V is associated with an eightfold increase in resistance to this PI as inferred from genotype-phenotype data. 2018 ACS omega Introduction HIV L76V 42 46 PI 110 112 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Inclusion of L76V in mutants bearing three other resistance mutations is associated with two- and eightfold increase in resistance to 1 and 2, respectively, and an eightfold increase in susceptibility to 6. 2018 ACS omega Introduction HIV L76V 13 17 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Mutation L76V is associated with clinical resistance to 1, fosamprenavir, 2, and indinavir; however, it is also linked with increased susceptibility to first-generation inhibitor saquinavir (6), atazanavir, and 3. 2018 ACS omega Introduction HIV L76V 9 13 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Previous studies of PR with the single mutation of L76V (PRL76V) showed about 100-fold worse inhibition by 1 compared to wild-type PR (PRWT) as assessed by isothermal titration calorimetry, although another group using an enzyme inhibition assay reported only 1.5-fold loss in potency. 2018 ACS omega Introduction HIV L76V 51 55 PR;PR;PR 20;57;131 22;59;133 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. The results show that these chemically diverse inhibitors lose potency against PRL76V, and suggest that local rearrangements in the hydrophobic core because of mutation L76V act to decrease the effectiveness of the inhibitors. 2018 ACS omega Introduction HIV L76V 169 173 PR 79 81 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. A recent study from the city of Sao Paulo10 on patients who failed first-line therapy between 2013 and 2015 found a higher prevalence of the M184 V/I mutation (74.3%) and K103 codon (56.7%), similar to that found in other Brazilian states. 2018 BMC infectious diseases Introduction HIV M184I;M184V 141;141 149;149 30346745 Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. Because the boronic acid moiety of 1 is anticipated to interact with Asp30, we suspected that D30N HIV-1 protease, which is a common variant that endows resistance, could compromise the affinity of boronic acid 1. 2018 Journal of the American Chemical Society Introduction HIV D30N 94 98 PR;Asp 105;69 113;72 30346745 Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. For example, the D30N substitution entices darunavir to form a water-bridge between its aniline nitrogen and the nascent asparagine, diminishing affinity by 30-fold. 2018 Journal of the American Chemical Society Introduction HIV D30N 17 21 30346745 Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. Remarkably, the affinity of boronic acid 1 for the D30N variant (Ki = 0.4 +- 0.3 pM) is indistinguishable from that for wild-type HIV-1 protease. 2018 Journal of the American Chemical Society Introduction HIV D30N 51 55 PR 136 144 30346745 Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. To understand the basis for the extraordinary affinity and resiliency of boronic acid 1, we determined the X-ray crystal structures of its complexes with both wild-type HIV-1 protease and the D30N variant. 2018 Journal of the American Chemical Society Introduction HIV D30N 192 196 PR 175 183 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. In four of the five prior published cases of HIV acquisition despite high PrEP adherence, the virus demonstrated an M184V mutation in reverse transcriptase (RT) conferring resistance to FTC, and three of these viruses also had resistance mutations conferring reduced susceptibility to TDF (K70R or K65R) (Table 1). 2018 The lancet. HIV Introduction HIV K65R;K70R;M184V 298;290;116 302;295;121 RT;RT 134;157 155;159 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Most of the patient-derived sequences bear a constellation of secondary mutations as well as primary mutations at the active site that confer DRV resistance, notably including I50V and I84V. 2019 ACS infectious diseases Introduction HIV I50V;I84V 176;185 180;189 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Mutations at I50 are often selected together with A71V mutation, which is distal from the active site but compensates for the loss of enzymatic fitness. 2019 ACS infectious diseases Introduction HIV A71V 50 54 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The hydrophobic residues I84, V82 and I50 that form the S1' pocket where the P1' moiety binds [Figure 1] (as well as the S1 pocket, as the protease is a homodimer) are all highly variable, and mutations are implicated in many instances of drug resistance, commonly mutating to I84V, V82I, and I50V in multi-mutant protease variants. 2019 ACS infectious diseases Introduction HIV I50V;I84V;V82I 293;277;283 297;281;287 PR;PR 139;314 147;322 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Thermodynamics and structural studies of DRV binding to I50V/L and A71V mutations have revealed significant loss of van der Waals (vdW) contacts between the inhibitor and protease underlying loss of binding affinity. 2019 ACS infectious diseases Introduction HIV A71V;I50L;I50V 67;56;56 71;62;62 PR 171 179 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. In a previous study, the virological outcomes of various tenofovir-based first-line regimens were similar when comparing 17 patients with M41L and 248 subjects with WT virus. 2019 The Journal of antimicrobial chemotherapy Introduction HIV M41L 138 142 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. More recently, investigators at Gilead Sciences merged data from a variety of clinical trials and reported that virological responses to 48 weeks of tenofovir-based first-line regimens were not diminished among 205 patients harbouring >=1 TAM, including 76 subjects with revertants of T215Y or T215F (T215rev. 2019 The Journal of antimicrobial chemotherapy Introduction HIV T215F;T215Y 294;285 299;290 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. However, the contribution of T97A to DTG resistance in the presence of other INSTI mutations has not been well described. 2018 Open forum infectious diseases Introduction HIV T97A 29 33 INSTI 77 82 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. T97A is an accessory mutation frequently co-selected with additional drug resistance mutations (DRMs) including Q148H and G140S in individuals failing raltegravir (RAL) or elvitegravir (EVG) therapy and contributes substantially to resistance to these first-generation INSTIs. 2018 Open forum infectious diseases Introduction HIV G140S;Q148H;T97A 122;112;0 127;117;4 INSTI 269 275 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. The T97A mutation emerged in both cases and was accompanied by a substantial decrease in DTG susceptibility. 2018 Open forum infectious diseases Introduction HIV T97A 4 8 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Even in naive patients, low frequencies of K103N and Y181C variants can lead to an increased risk of virologic failure. 2019 Journal of medicinal chemistry Introduction HIV K103N;Y181C 43;53 48;58 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. However, 3 exhibited weaker efficacy toward the particularly challenging double-mutation variant strain RES056 (K103N+Y181C) (EC50 = 30.6 nM) compared with ETV (EC50 = 17.0 nM). 2019 Journal of medicinal chemistry Introduction HIV K103N;Y181C 112;118 117;123 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. In particular, the K103N and Y181C mutations are prevalent in clinical HIV-1 isolates. 2019 Journal of medicinal chemistry Introduction HIV K103N;Y181C 19;29 24;34 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. A number of additional mutations observed in patients can increase DTG resistance, including L74M and E138K. 2019 Open forum infectious diseases Introduction HIV E138K;L74M 102;93 107;97 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. Dolutegravir monotherapy in naive patients, on the other hand, is associated with more frequent selection of drug resistance mutations such as R263K, G118R, S230, and possibly resistance mutations outside the integrase gene. 2019 Open forum infectious diseases Introduction HIV G118R;R263K 150;143 155;148 IN 209 218 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. DTG appears to have a high genetic barrier to resistance, unlike the other drugs within the INSTI class, raltegravir and elvitegravir, which select for major resistance mutations such as N155H, Y143H/R/C, G140A/S, and Q148H/R/K. 2019 Open forum infectious diseases Introduction HIV G140A;G140S;N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 205;205;187;218;218;218;194;194;194 212;212;192;227;227;227;203;203;203 INSTI 92 97 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. In low-middle-income settings, R263K and other DTG resistance mutations may be more common where patients remain on failing regimens for longer periods of time and use alternate NRTIs temporarily due to stockouts or undisclosed ARV use, thereby accumulating multi-NRTI resistance. 2019 Open forum infectious diseases Introduction HIV R263K 31 36 NRTI;NRTI 178;264 183;268 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. Most reports of the R263K mutation stem from subtype B-infected individuals in high-income settings treated with ABC/3TC/DTG or DTG monotherapy. 2019 Open forum infectious diseases Introduction HIV R263K 20 25 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. The integrase mutation R263K confers moderate resistance to DTG with a significant reduction of in vitro replication fitness. 2019 Open forum infectious diseases Introduction HIV R263K 23 28 IN 4 13 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. However, the landscape of antiretrovirals is changing continuously and new mutations such as E138A/G/K/Q/R (that confers resistance to the NNRTI rilpivirine (RPV), approved in 2011) are therefore not covered by this list. 2019 PloS one Introduction HIV E138A;E138G;E138K;E138Q;E138R 93;93;93;93;93 106;106;106;106;106 NNRTI 139 144 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. In our study, the analysis of TDRMs was therefore based on the Stanford HIVdb SDRM list, which is updated regularly and includes all mutations in the WHO SDRM list apart from F53Y and V85I in protease. 2019 PloS one Introduction HIV F53Y;V85I 175;184 179;188 PR 192 200 30788976 Synthesis and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors. K103N and Y181C for NNRTIs), continuous effort has identified a number of new NNRTI drug candidates. 2019 Antiviral chemistry & chemotherapy Introduction HIV Y181C;K103N 10;0 15;5 NNRTI;NNRTI 20;78 26;83 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. In this communication, we have examined the consequences of the naturally occurring R57S substitution on Tat uptake by bystander cells via a wider dissemination of inflammation through activation of proinflammatory genes. 2019 Scientific reports Introduction HIV R57S 84 88 Tat 105 108 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. This R57S substitution reduces the number of CPP basic residues (arginine or lysine) from eight in non-clade C Tat proteins to seven in Tat-C. 2019 Scientific reports Introduction HIV R57S 5 9 Tat;Tat 111;136 114;139 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. We and others have shown that a naturally occurring polymorphism in Tat, a cysteine to serine substitution at residue 31 (C31S) significantly reduces its neuropathogenic potential, diminishing Tat's ability to recruit MPs, its neurotoxicity and its pro-inflammatory function. 2019 Scientific reports Introduction HIV C31S;C31S 122;75 126;120 Tat;Tat 68;193 71;196 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. We explored the effect of R57S substitution on the uptake of full-length Tat proteins, using a transcellular transactivation assay where we show a significant reduction. 2019 Scientific reports Introduction HIV R57S 26 30 Tat 73 76 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. For example, DA uptake is decreased in K92M and increased in H547A, respectively; however Y88F mutant preserves basal DA uptake. 2019 Scientific reports Introduction HIV H547A;K92M;Y88F 61;39;90 66;43;94 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Single point mutations of hDAT at tyrosine88 (to phenylalanine, Y88F), lysine 92 (to methionine, K92M), histidine547 (to alanine, H547A) differentially alter basal DA uptake but attenuate the Tat inhibitory effects on DA transport. 2019 Scientific reports Introduction HIV H547A;K92M;Y88F 130;97;64 135;101;68 Tat 192 195 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Therefore, this study investigated the mutational effects of Y88F/H547A and Y88F/K92M/H547A on basal DAT function, Tat inhibitory effect on DA uptake, and dynamic DA transport process. 2019 Scientific reports Introduction HIV H547A;K92M;Y88F;H547A;Y88F 86;81;76;66;61 91;85;80;71;65 Tat 115 118 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Studies of drug resistance mutations (DRMs) in plasma virus ribonucleic acid (RNA) by Sanger consensus sequencing frequently identify mutations associated with nonnucleoside reverse-transcriptase inhibitors (NNRTIs); most often K103N, followed by G190S, V106A/M, Y181C, Y188L, and P225H. 2019 Open forum infectious diseases Introduction HIV G190S;K103N;P225H;V106A;V106M;Y181C;Y188L 247;228;281;254;254;263;270 252;233;286;261;261;268;275 NNRTI;NNRTI 160;208 195;214 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. To evaluate the retention and decay of DRMs after the emergence of plasma resistance, we identified participants with known dates of failure of an EFV-based regimen with the K103N mutation in plasma RNA by population sequencing. 2019 Open forum infectious diseases Introduction HIV K103N 174 179 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. Among other commonly detected vaccine-escape mutants are: P120Q, Q129H, F134Y/L, S143L and D144A/E. 2019 PeerJ Introduction HIV F134L;F134Y;S143L 72;72;81 79;79;86 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. In such situations, 3TC could be recycled as part of the NRTI-backbone in SLC because it selects for the M184 V mutation, which decreases viral replication and increases susceptibility to AZT and TDF for potential use in SLC with PI/r. 2019 BMC infectious diseases Introduction HIV M184V 105 111 NRTI;PI 57;230 61;232 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Of note, failure on TDF leads to viral hyper-susceptibility to AZT (due to K65R mutation) while failure on AZT leads to possible cross-resistance to TDF. 2019 BMC infectious diseases Introduction HIV K65R 75 79 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Compound 13 is similar to RPV in terms of its therapeutic index and its antiretroviral efficacy against a panel of HIV-1 mutants containing RT mutations, including L100I, K103N, V106A, E138K, Y181C, Y188L, H221Y, and K103N/Y181C. 2019 Journal of virology Introduction HIV E138K;H221Y;K103N;K103N;L100I;V106A;Y181C;Y181C;Y188L 185;206;171;217;164;178;192;223;199 190;211;176;222;169;183;197;228;204 RT 140 142 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. E138K was the mutation present at the highest frequency. 2019 Journal of virology Introduction HIV E138K 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Here we report that HIV-1 replicating in the presence of compound 13 coselected two mutations in RT (G112D and M230I), which were analyzed using biochemical and virological assays to understand their role(s) in drug susceptibility and their effects on HIV-1 replication. 2019 Journal of virology Introduction HIV G112D;M230I 101;111 107;116 RT 97 99 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. In those trials, the viruses in participants who failed RPV-containing therapies had the RT mutations L100I, K101E, K103N, V108I, E138K/R, Y181C, and/or M230L. 2019 Journal of virology Introduction HIV E138K;E138R;K101E;K103N;L100I;M230L;V108I;Y181C 130;130;109;116;102;153;123;139 137;137;114;121;107;158;128;144 RT 89 91 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. 4a, b):the unliganded HIV-1JR-FL Env labelled in V4-A1 of gp120 and on Arg542TAG in the alpha6 helix of gp41 (alpha6-Arg542TAG) largely exhibited a high-FRET state. 2019 Nature Introduction HIV R542A;R542G;R542T 71;71;71 80;80;80 gp120;gp41;Env 58;104;33 63;108;36 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Here we measured Env conformational dynamics using a click-labelled unnatural amino acid at residue 542 (Arg542TAG) within gp41, in combination with the A1 enzymatic labelling tag in the gp120 V4 region (V4-A1) (Extended Data. 2019 Nature Introduction HIV R542A;R542G;R542T 105;105;105 114;114;114 gp120;gp41;Env 187;123;17 192;127;20 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. HIV-1JR-FL with the Env labelled at Asn136 in V1 and V4-A1 or with the Env labelled at Arg542TAG in alpha6 and V4-A1 was immobilized and continuously monitored over 60 min, after addition of eCD4-Ig(Q40A, mim2) (100 mug ml-1). 2019 Nature Introduction HIV Q40A;R542A;R542G;R542T 199;87;87;87 203;96;96;96 Env;Env 20;71 23;74 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. To understand the predominance of the state-2 conformation in BG505 sgp140 SOSIP.664, we introduced the SOSIP changes (that is, the disulfide bond and I559P substitution):both separately and in combination:into the native HIV-1BG505 Env. 2019 Nature Introduction HIV I559P 151 156 Env 233 236 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. We further monitored how HIV-1 Env is progressively activated by the potent bifunctional inhibitor eCD4-Ig(Q40A, mim2). 2019 Nature Introduction HIV Q40A 107 111 Env 31 34 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. Different pathways against first-generation InSTIs were identified whose primary mutations include the substitutions N155H, Q148K/R/H, and Y143R/C. 2019 Revista espanola de quimioterapia Introduction HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 117;124;124;124;139;139 122;133;133;133;146;146 INSTI 44 50 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. An additional concern is the lack of information on the mutations selected with CAB in vivo and their potential impact on resistance to other INSTIs, as only two cases of CAB resistance have been reported in HIV-infected patients treated with CAB, both mediated by integrase mutation Q148R. 2019 Nature communications Introduction HIV Q148R 284 289 IN;INSTI 265;142 274;148 HIV infections 208 220 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. We show selection of integrase mutations G118R, G140R, and E92Q/G with CAB-LA, and demonstrate phenotypic resistance to CAB and cross-resistance to all licensed integrase inhibitors including raltegravir (RAL), elvitegravir (EVG), DTG, and bictegravir (BIC). 2019 Nature communications Introduction HIV E92G;E92Q;G118R;G140R 59;59;41;48 65;65;46;53 IN;IN 21;161 30;170 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. HIV-1 PR with drug resistant mutations V32I, I47V and V82I (PRTri) has been evaluated as a model for inhibition of HIV-2 PR to overcome the problem of autoproteolysis of HIV-2 PR. 2019 Biochemical and biophysical research communications Introduction HIV I47V;V32I;V82I 45;39;54 49;43;58 PR;PR;PR 6;121;176 8;123;178 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. Moreover, the individual mutations of V32I, I47V and V82I are associated with resistance to one or more clinical inhibitors. 2019 Biochemical and biophysical research communications Introduction HIV I47V;V32I;V82I 44;38;53 48;42;57 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In the current study, we use structural and kinetic studies on PR, PRS17-D25N, and PRS17 with substrate analogues CA-p2 (R-V-L-r-F-E-A-Nle) and p2-NC (Ace-T-I-Nle-r-Nle-Q-R) to evaluate differences in substrate recognition between PRS17 and wild-type PR. 2019 ACS omega Introduction HIV D25N 73 77 NC;Capsid;PR;PR;PR;PR;PR 147;114;63;67;83;231;251 149;116;65;69;85;233;253 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. A study has shown that a single point mutation in tetherin T45I was successful in rendering tetherin resistant to Vpu-mediated depletion, while numerous other studies dealing with identification of interacting points between the two proteins have put forth positions crucial for binding and mutations in them affecting their binding potential. 2019 Medical sciences (Basel, Switzerland) Introduction HIV T45I 59 63 Vpu 114 117 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. The lamivudine (3TC, an NRTI drug) mutation M184V and the efavirenz (EFV) and nevirapine (NVP) (two NNRTI drugs) mutations K103N and 181C are frequently observed in cases of virological failure. 2019 Sexually transmitted infections Introduction HIV K103N;M184V 123;44 128;49 NNRTI;NRTI 100;24 105;28 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. A newer generation of NNRTIs was developed in an effort to successfully target drug resistant forms, including Y181C, which evade inhibition by early generation NNRTIs. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 111 116 NNRTI;NNRTI 22;161 28;167 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Analysis of key interactions reveals the conservation of hydrogen bonding and van der Waals forces between the WT and Y181C structures. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 118 123 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Clear electron density was observed at the NNRTI binding pocket, allowing unambiguous determination of the orientation and positioning of the 2-cyanoindolizine catechol diether scaffold of Compound 1 for both the WT RT and Y181C structures (Figure 3). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 223 228 NNRTI;RT 43;216 48;218 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Comparison of van der Waals sphere visualization of the WT and Y181C structures shows that WT RT packs more tightly around Compound 1 compared to Y181C RT (Supplemental Figure 3). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C;Y181C 63;146 68;151 RT;RT 94;152 96;154 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Despite the shifting of the ethoxy uracil ring in our Y181C RT:Compound 1 structure, we see that both WT and Y181C RT contain three hydrogen bonds between the uracil ring and the L103/P236 residues, further suggesting that the interaction involving the halogen helps position the ethoxy uracil ring to preserve favorable interaction with its neighboring residues. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C;Y181C 54;109 59;114 RT;RT 60;115 62;117 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Effective inhibition of WT and Y181C HIV-infected cells suggests that Compound 1 has potent inhibitory activity against WT and Y181C strains of HIV-1. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C;Y181C 31;127 36;132 HIV infections 37 49 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Further, this flexibility may explain why the Y181C mutation does not necessarily result in a loss of potency with the catechol diether series of NNRTIs. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 46 51 NNRTI 146 152 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. However, in place of the lost tyrosine, we see compensatory van der Waals interactions in our Y181C structure. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 94 99 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Importantly, superimposition of our two reported structures show that the Y181C mutation in the p66 subunit did not cause large scale conformational changes in the RT fold, and thus, analysis of intermolecular interactions between RT and our compound of interest at the NNRTI binding pocket can be accounted for the difference in potencies observed in our steady state kinetic assays. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 74 79 NNRTI;RT;RT 270;164;231 275;166;233 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Importantly, the EC50 values from our viral infectivity assay for both WT and Y181C strains were comparable to the IC50 values observed in our in vitro enzymatic assay (Figure 2, Supplemental Figure 2). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 78 83 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. In a similar sense, in our Y181C RT:Compound 1 crystal structure, the binding pocket offers a higher level of conformational freedom by the NNRTI, possibly explaining how the flexibility of the binding pocket allows improved binding of the NNRTI, leading to the maintenance of high potency in a drug resistant mutant of RT despite the loss of stacking interaction and van der Waals interaction upon mutation of Y181. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 27 32 NNRTI;NNRTI;RT;RT 140;240;33;320 145;245;35;322 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. In order to determine the relative potencies of Compound 1 against WT RT and Y181C RT, a biochemical inhibition assay was used that utilizes PicoGreen, a fluorescent dye that detects formation of dsDNA, dsRNA, and hybrid RNA-DNA strands, as reported previously (Figure 2A; experimental methods available in Supplementary Data). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 77 82 RT;RT 70;83 72;85 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. In order to determine the structural basis of Compound 1 inhibition of both WT and Y181C RT, the crystal structure of each construct in complex with the inhibitor was solved (PDB: 6DTX and 6DTW, respectively; experimental methods available in Supplementary Data). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 83 88 RT 89 91 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. In our present structures, we find that the 6-fluorine substituent on the indolizine ring makes close contact with sidechain carbons of P95 for both WT RT and Y181C structures. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 159 164 RT 152 154 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. One specific RT mutation wherein a tyrosine residue in the NNRTI pocket is mutated to a cysteine (Y181C) is among the most prevalent drug resistant mutation, observed to rapidly emerge after administration of NNRTIs including nevirapine, delavirdine, and other first-generation NNRTIs. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 98 103 NNRTI;NNRTI;NNRTI;RT 59;209;278;13 64;215;284;15 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Our previous assays suggested very potent activity on WT strains of HIV-1 IIIB but less effective on a clinical isolate (HIV-1 N119) containing the nevirapine-resistant Y181C mutation. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 169 174 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Remarkably, Compound 1 maintains high potency against Y181C RT, with an IC50 value of 5.5 +- 1.1 nM (Figure 2C). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 54 59 RT 60 62 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Such a compensatory interaction likely results in conservation of the energetic stability of Compound 1 binding in the NNRTI pocket, and this may explain the similar potencies of Compound 1 against WT and Y181C RT in our steady state RT assays. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 205 210 NNRTI;RT;RT 119;211;234 124;213;236 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Surprisingly, in the structure of Compound 1 in complex with Y181C RT, we find that the interatomic distance between the fluorine and the Cgamma of P95 is a nearly identical 3.5 A, indicating that the NNRTI maintains close contact with P95 despite the Y181C mutation (Figure 7B). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C;Y181C 61;252 66;257 NNRTI;RT 201;67 206;69 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. The current study utilized molecular clones of HIV-1 pNL4-3 containing WT or Y181C mutation. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 77 82 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. The IC50 and EC50 values, in biochemical and cellular assays, of Compound 1 against WT and Y181C RT are remarkably similar, and structural data suggest that several critical NNRTI-RT interactions are maintained with the Y181C mutant to rationalize the in vitro and cellular potency. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C;Y181C 91;220 96;225 NNRTI;RT;RT 174;97;180 179;99;182 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. The root-mean-square deviation (RMSD) values after superimposition of the NNRTI binding pocket of WT RT:Compound 1 and Y181C RT:Compound 1 was 0.765 A, suggesting that the fold of the three-dimensional structure around the NNRTI binding pocket are well conserved in both structures. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 119 124 NNRTI;NNRTI;RT;RT 74;223;101;125 79;228;103;127 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. The Y181C mutation abrogates this stacking interaction by replacement of an aromatic side chain with a cysteine. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 4 9 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Three backbone hydrogen bonds still exist between K103/P236 and the uracil ring for both structures, suggesting that the Y181C mutation does not cause significant loss of interactions between the NNRTI and RT (Figure 5). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 121 126 NNRTI;RT 196;206 201;208 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Thus, in light of drug resistant mutations such as Y181C, these NNRTIs can no longer bind as effectively. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 51 56 NNRTI 64 70 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. Upon examining the overlay of our two structures, we observe that the Y181C mutation slightly shifts the catechol ring closer to the side chain of V179 similar to previously reported crystal structures of catechol diether compounds. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 70 75 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. We determined two crystal structures where Compound 1 was crystallized with WT and Y181C mutant RT. 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C 83 88 RT 96 98 31281023 Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase. We observed a concentration-dependent inhibition of HIV-1 infection for both WT and Y181C mutant RT, and an EC50 of 3.2 nM for Y181C, similar to the WT EC50 of 4.7 nM, was determined (Figure 1B, Supplemental Figure 2). 2019 Bioorganic & medicinal chemistry letters Introduction HIV Y181C;Y181C 84;127 89;132 RT 97 99 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. As DRV binds wild-type (WT) sequences of HIV-1 protease with high affinity (<5pM), binding assays are generally not adequately sensitive to detect the relative impact of the L89V and L90M single amino acid substitutions. 2019 Biochemistry Introduction HIV L89V;L90M 174;183 178;187 PR 47 55 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. As with most other primary resistance-associated mutations in HIV-1 protease, L90M alone is not known to confer resistance against DRV. 2019 Biochemistry Introduction HIV L90M 78 82 PR 68 76 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Both the L89V and L90M mutations are present in the KY variant protease sequence, so constructs containing back-mutations at each of these residues were purified. 2019 Biochemistry Introduction HIV L89V;L90M 9;18 13;22 PR 63 71 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. However, the L90M mutation has previously been reported to alter the geometry of the main chain of the D25 residue, causing a slight dislocation of the catalytic residue, thereby altering the protein-ligand interactions and dimer stability. 2019 Biochemistry Introduction HIV L90M 13 17 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In this study, we focus on a pair of amino acid substitutions within the protease, L89V and L90M, where non-additivity has been previously reported in HIV-1 subtypes B and G without being extensively characterized. 2019 Biochemistry Introduction HIV L89V;L90M 83;92 87;96 PR 73 81 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Likewise, the L90M mutation is associated with resistance to a variety of protease inhibitors, including atazanavir, indinavir, lopinavir, saquinavir, nelfinavir and darunavir. 2019 Biochemistry Introduction HIV L90M 14 18 PR 74 82 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. One such example is the A71V mutation, a secondary mutation that, when observed in conjunction with I50V/L, acts to restore a balance between catalytic efficiency and inhibitor binding. 2019 Biochemistry Introduction HIV A71V;I50L;I50V 24;100;100 28;106;106 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Primary drug resistant mutations, such as I50V and I84V, occur proximal to the active site and impact inhibitor binding by altering the direct interactions between the protease and inhibitor. 2019 Biochemistry Introduction HIV I50V;I84V 42;51 46;55 PR 168 176 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The L89V mutation in HIV-1 protease is a so-called accessory mutation that is present in patient-derived isolates and is associated with resistance to DRV inhibition. 2019 Biochemistry Introduction HIV L89V 4 8 PR 27 35 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The L90M mutation also has been shown to confer resistance to nelfinavir by perturbing the catalytic residues and the sidechain of residue 84, leading to a loss of affinity with the inhibitor. 2019 Biochemistry Introduction HIV L90M 4 8 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The non-additivity of the L89V and L90M mutations in subtype B has been noted on the basis of a significant positive correlation between the two mutations in a large sample of HIV-1 protease sequences derived from subjects treated with a variety of protease inhibitors, suggesting an enhanced beneficial effect of the double mutant on the fitness of the virus under treatment by these drugs. 2019 Biochemistry Introduction HIV L89V;L90M 26;35 30;39 PR;PR 182;249 190;257 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. These constructs are referred to as KY(V89L) and KY(M90L), respectively, along with a construct that had both mutations reversed, KY(V89L/M90L) that is henceforth referred to as "KY(DM)" for the sake of nomenclature compactness (Figure 1A). 2019 Biochemistry Introduction HIV M90L;M90L;V89L;V89L 52;138;39;133 56;142;43;137 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. To study the interdependence of the L89V and L90M mutations, the consensus HIV-1 protease variant from a patient-derived isolate that exhibits little susceptibility to DRV inhibition provided a useful reference. 2019 Biochemistry Introduction HIV L89V;L90M 36;45 40;49 PR 81 89 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The variant has the following mutations; E35D, I36G, two insertions at position 35 (G and S), and D60E and is referred to as E35D G S (Figure S1) with the upward arrows showing positions of insertions. 2019 Journal of enzyme inhibition and medicinal chemistry Introduction HIV D60E;E35D;E35D;I36G 98;41;125;47 102;45;129;51 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. This mutant is also different from the I36T T mutant as bears to insertions compared to just one from the former. 2019 Journal of enzyme inhibition and medicinal chemistry Introduction HIV I36T 39 43 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. An interesting property of this RGDA/Q112D virus is its behavior in cells coinfected with Sendai virus (SeV). 2019 Journal of virology Introduction HIV Q112D 37 42 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. As SeV attenuates a type I IFN-induced antiviral state, we hypothesized that the RGDA/Q112D mutant is hypersensitive to type I IFN. 2019 Journal of virology Introduction HIV Q112D 86 91 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Coinfection of target cells with SeV enhanced the infectivity of the RGDA/Q112D virus but not that of the wild-type (WT) virus. 2019 Journal of virology Introduction HIV Q112D 74 79 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Importantly, the Q4R mutation accelerated the kinetics of the completion of reverse transcription and the initiation of uncoating of the RGDA/Q112D virus, whereas the reverse transcription kinetics of the RGDA/Q112D virus were also accelerated by the G94D/G116R mutations. 2019 Journal of virology Introduction HIV G116R;G94D;Q112D;Q112D;Q4R 256;251;142;210;17 261;255;147;215;20 RT;RT 76;167 97;188 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In this study, we used this RGDA/Q112D virus as a tool to study the interplay between HIV-1 CA and type I IFN-mediated restriction. 2019 Journal of virology Introduction HIV Q112D 33 38 Capsid 92 94 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Specifically, it was reported that the CypA binding-deficient CA mutant (the P90A mutant) and the CPSF6 binding-deficient CA mutant (the N74D and A105T mutant) are more sensitive than wild-type (WT) CA to IFN alpha (IFN-alpha) in monocyte-derived THP-1 cells. 2019 Journal of virology Introduction HIV A105T;N74D;P90A 146;137;77 151;141;81 Capsid;Capsid;Capsid 62;122;199 64;124;201 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We first demonstrate that the RGDA/Q112D virus is indeed highly sensitive to IFN-beta in Jurkat T cells. 2019 Journal of virology Introduction HIV Q112D 35 40 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We found that a single Q4R mutation or the double substitutions G94D/G116R in CA emerged during adaptation and conferred IFN-beta resistance upon transfer to the parental RGDA/Q112D virus. 2019 Journal of virology Introduction HIV G116R;G94D;Q112D;Q4R 69;64;176;23 74;68;181;26 Capsid 78 80 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We next performed adaptation of the RGDA/Q112D virus in IFN-beta-treated Jurkat cells to ask how a highly IFN-beta-sensitive virus evolves to overcome capsid-targeting restriction by type I IFN. 2019 Journal of virology Introduction HIV Q112D 41 46 Capsid 151 157 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We recently reported that one mutant virus, called the RGDA/Q112D virus, which contains the H87R, A88G, P90D, P93A, and Q112D changes in CA, was highly resistant to cynomolgus monkey (CM) TRIMCyp. 2019 Journal of virology Introduction HIV A88G;H87R;P90D;P93A;Q112D;Q112D 98;92;104;110;60;120 102;96;108;114;65;125 Capsid 137 139 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The inferred unmutated common ancestor (UCA) of the CH235/CH235.12 lineage, referred to here as CH235 UCA2, exhibits micromolar affinity binding and weak neutralizing activity against an early autologous CH505 Env that differs from the transmitted-founder (TF) Env by a single N279K change, suggesting that this variant (also called M5) initiated the lineage. 2019 PLoS pathogens Introduction HIV N279K 277 282 Env;Env 210;261 213;264 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. In the early stages of therapy, the mutation N155H tends to appear and can be later substituted by either the Y143R or Q148HKR pathway after prolonged treatment. 2019 Frontiers in microbiology Introduction HIV N155H;Q148H;Q148K;Q148R;Y143R 45;119;119;119;110 50;126;126;126;115 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Subsequent reports identified Gag V362I (15.4% of the subtype B Los Alamos National Labs [LANL] database) as another major polymorphic variant conferring reduced bevirimat susceptibility. 2019 PloS one Introduction HIV V362I 34 39 Gag 30 33 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. We examine the link between DP closing and substrate unbinding by studying both WT and F99Y mutant PR. 2019 The journal of physical chemistry. B Introduction HIV F99Y 87 91 PR 99 101 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Expanding on our earlier work that selected for viral resistance to PIE12-trimer, here we describe the biochemical, structural, and functional properties of the primary PIE12-trimer resistance mutations (Q577R/N/K). 2019 Retrovirology Introduction HIV Q577K;Q577N;Q577R 204;204;204 213;213;213 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Through comprehensive characterization of the genotype of our PIE12-trimer resistant viral populations via next-generation sequencing, we identify potential compensatory mutations in HIV Env that restore fitness in the context of Q577R/N/K. 2019 Retrovirology Introduction HIV Q577K;Q577N;Q577R 230;230;230 239;239;239 Env 187 190 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Furthermore, the 2015 changes in the French National Agency for AIDS Research resistance algorithms highlighted the risk of the impaired efficacy of ABC in the presence of the M184V/I mutation, as previously observed for 3TC. 2019 Open forum infectious diseases Introduction HIV M184I;M184V 176;176 183;183 AIDS 64 68 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Thus, the clinical decision to switch to an ABC/3TC/DTG regimen could be influenced by a patient having evidence of harboring a M184V/I mutation, which leads to 3TC resistance and may potentially impair the effectiveness of both 3TC and, to a lesser extent ABC, thus resulting in a treatment representing functional DTG monotherapy. 2019 Open forum infectious diseases Introduction HIV M184I;M184V 128;128 135;135 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. We conducted a prospective study using data from 5 large HIV cohorts in four European countries (France, Italy, the Netherlands and Switzerland) to assess the efficacy of the ABC/3TC/DTG regimen in virologically-suppressed, ART-experienced patients, with or without a previously documented M184V/I mutation. 2019 Open forum infectious diseases Introduction HIV M184I;M184V 290;290 297;297 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Several Nef mutations are reported to impair its ability to antagonize SERINC5, including G2A, D123A, and LL165AA, which block myristoylation, dimerization, and interaction with AP-2 trafficking complexes, respectively; however, while HIV-1 nef exhibits extensive genetic diversity, these mutations are rare in circulating viral strains (all >99% conserved; HIV Sequence Database, https://www.hiv.lanl.gov). 2019 Cell reports Introduction HIV D123A;G2A 95;90 100;93 Nef;Nef 8;241 11;244 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. For example, studies have shown, subtype C may acquire the tenofovir-related mutation K65R more rapidly when compared to subtype B, while mutations associated with resistance to rilpivirine are rare in infected patients with HIV-1 subtypes CRF01-A/E failing a first-line NNRTI-containing regimen. 2019 PloS one Introduction HIV K65R 86 90 NNRTI 271 276 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The majority of persons were infected with HIV-1 subtype B (89%) and phylogenetic inference identified eight local transmission clusters (TC), among which the largest TC harboured T215S mutation and consisted of 19 Croatian patients. 2019 Scientific reports Introduction HIV T215S 180 185 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The most frequently found mutation was the revertant T215S (14.4%), associated with resistance to nucleoside analogues reverse transcriptase inhibitors (NRTIs), while TDR associated with resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was detected in three persons (2.4%) and primary resistance to protease inhibitors (PIs) was not reported during that study period. 2019 Scientific reports Introduction HIV T215S 53 58 NNRTI;RT;PR;NNRTI;NRTI;PI 201;119;321;250;153;342 237;140;329;256;158;345 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Among Agno targets, interaction of Agno with Rab11B, Importin and Exportin/Crm-1 was validated by protein-protein interaction studies and further characterized for Agno-Crm-1 interaction using a HIV-1 Rev-M10 like mutant of Agno, (L33D + E34L) in the viral background. 2020 Virology Introduction HIV E34L;L33D 238;231 242;236 Rev 201 204 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. For example, early studies showed that in patients receiving 3TC monotherapy, or dual therapy with AZT/3TC, VL did not return to baseline despite the development of M184V. 2020 The Journal of infectious diseases Introduction HIV M184V 165 170 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. M184V/I are the most commonly occurring drug-resistant mutations in persons with acquired resistance to first-generation NNRTI-containing regimens. 2020 The Journal of infectious diseases Introduction HIV M184I;M184V 0;0 7;7 NNRTI 121 126 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Therefore, to understand the relationship between M184I/V and VL in the era of tenofovir-based cART in which thymidine analog mutations (TAMs) were not present, and also in the context of limited or no access to VL monitoring, we studied individuals failing the WHO-recommended first-line regimen of TDF/XTC/NNRTI across a range of settings. 2020 The Journal of infectious diseases Introduction HIV M184I;M184V 50;50 57;57 NNRTI 308 313 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Among them, a glutamic acid to glycine substitution, a glutamic acid to aspartic acid substitution and a glutamic acid to lysine substitution at position 560 (E560G, E560D, and E560K, respectively) in HR1 (according to HXB2 numbering) were found from a patient under T20 therapy. 2019 Retrovirology Introduction HIV E560D;E560G;E560K;E560K 166;159;177;105 171;164;182;157 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. And the E560K substitution was also found under IZN36 peptide selection. 2019 Retrovirology Introduction HIV E560K 8 13 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Interestingly, the resistance mutations occurred under N peptide inhibitor N36 and N44 selections by two pathways, either E560K mutation in HR1 or a glutamic acid to lysine substitution at position 648 (E648K) in HR2. 2019 Retrovirology Introduction HIV E560K;E648K;E648K 122;203;149 127;208;201 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The former two substitutions (E560G and E560D) were also found in cell cultures under the selection pressure of T20 in vitro (our unpublished data) and one mutation E560K was found from resistance cultures to N peptide inhibitors, respectively. 2019 Retrovirology Introduction HIV E560D;E560G;E560K 40;30;165 45;36;170 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The molecular modeling analysis also revealed the possible conformational changes of the E560K/D/G mutations indicating that the residue at the position 560 could regulate Env conformations through interactions with gp120 and HR2 of gp41. 2019 Retrovirology Introduction HIV E560D;E560G;E560K 89;89;89 98;98;98 gp120;gp41;Env 216;233;172 221;237;175 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The mutation E560K conferred resistance to N36 and IZN36 through increasing endogenous 6HB stability, but E560G or E560D as compensatory mutations destabilized the 6HB to reduce inhibitor binding and resulted in increased resistance to T20. 2019 Retrovirology Introduction HIV E560D;E560G;E560K 115;106;13 120;111;18 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. To investigate the property and resistance mechanisms of these substitutions at position 560 in HR1, we constructed HIV-1 LAI pseudoviruses bearing Env with mutations E560K/D/G. 2019 Retrovirology Introduction HIV E560D;E560G;E560K 167;167;167 176;176;176 Env 148 151 31827312 Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data. ACTG 244 enrolled HIV-infected patients receiving zidovudine (ZDV) monotherapy, and monitored them every eight weeks for occurrence of the 215 (T215Y/F) ZDV resistance mutation. 2019 The Canadian journal of statistics Introduction HIV T215F;T215Y 144;144 151;151 HIV infections 18 30 31827312 Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data. ACTG 244 enrolled HIV-infected patients taking zidovudine (ZDV) monotherapy and monitored their HIV in plasma every eight weeks for presence of the T215Y/F ZDV resistance mutation. 2019 The Canadian journal of statistics Introduction HIV T215F;T215Y 148;148 155;155 HIV infections 18 30 31827312 Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data. In conclusion, switching to the combination therapies based on the T215Y mutation has positive benefits as compared to continuing with ZDV monotherapy ZDV even after drug-resistant virus was detected. 2019 The Canadian journal of statistics Introduction HIV T215Y 67 72 31827312 Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data. Let S1 be the time between the dates of study entry and the first randomization triggered by occurrence of the T215Y/F mutation, such that U1(t) = t - S1 is the follow-up time starting at the date of the first randomization. 2019 The Canadian journal of statistics Introduction HIV T215F;T215Y 111;111 118;118 31827312 Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data. Of 289 enrolled participants, 5 were randomized but went off study before taking any medication, 284 were dispensed ZDV, and 57 developed T215Y/F during follow-up, of whom 49 were randomized to ZDV (n = 17), ZDV+ddI (n = 15), or ZDV+ddI+NVP (n = 17). 2019 The Canadian journal of statistics Introduction HIV T215F;T215Y 138;138 145;145 31827312 Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data. The observed P -values shown in the second block of Table 5 suggests that switching to the combination therapies ZDV+ddI and ZDV+ddI+NVP both improve CD4 counts for patients without having yet developed the T215Y drug resistance mutation. 2019 The Canadian journal of statistics Introduction HIV T215Y 207 212 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. As a single amino acid residue mutation, M184V confers very high resistance to FTC and 3TC as compared to WT (>500-fold). 2019 Communications biology Introduction HIV M184V 41 46 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Both in vitro and in vivo experiments have shown that FTC and 3TC primarily select for resistance mutations, M184V or M184I. 2019 Communications biology Introduction HIV M184I;M184V 118;109 123;114 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Furthermore, binary (M184V-DNA), and ternary structures with (-)-FTC-TP and dCTP were determined to better understand the mechanism by which the M184V mutation confers resistance to NRTIs. 2019 Communications biology Introduction HIV M184V;M184V 21;145 26;150 NRTI 182 187 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Herein, using the same DNA construct, we report the pre-steady-state kinetic analysis with WT RT and M184V to determine the incorporation efficiency of both (+)- and (-)-enantiomers of FTC-TP and 3TC-TP compared to dCTP in addition to crystal structures of WT RT in complex with dsDNA (RT-DNA) bound to either, (-)-FTC-TP, (-)-3TC-TP, (+)-FTC-TP, or dCTP. 2019 Communications biology Introduction HIV M184V 101 106 RT;RT;RT 94;260;286 96;262;288 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. M184V arises from a two nucleotide change but it outcompetes M184I and is observed in most patients with virologic failure resulting from FTC or 3TC treatment. 2019 Communications biology Introduction HIV M184I;M184V 61;0 66;5 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Several groups have explored whether M184V confers NRTI resistance by reducing binding affinities of these L-nucleotide analogs by the HIV-1 RT or whether it affects the rates of L-nucleotide analog incorporation. 2019 Communications biology Introduction HIV M184V 37 42 NRTI;RT 51;141 55;143 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. suggested that the M184V mutation primarily affects the rate of incorporation of the L-nucleotide analogs. 2019 Communications biology Introduction HIV M184V 19 24 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The M184I mutation will often emerge first, possibly because it results from a single nucleotide change. 2019 Communications biology Introduction HIV M184I 4 9 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The M184V mutation has been shown to have multiple effects on RT activity and resistance. 2019 Communications biology Introduction HIV M184V 4 9 RT 62 64 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The mechanism of M184V resistance to FTC and 3TC has been debated in the literature. 2019 Communications biology Introduction HIV M184V 17 22 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. These comprehensive kinetic and structural studies provide the most definitive insights into the binding modes of oxathiolane analogs and the mechanism of NRTI resistance achieved by the M184V mutation of HIV-1 RT. 2019 Communications biology Introduction HIV M184V 187 192 NRTI;RT 155;211 159;213 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. using gel shift assays, demonstrated reduced rates of L-nucleotide analog incorporation by the M184V mutant with no effect on their binding. 2019 Communications biology Introduction HIV M184V 95 100 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. While M184V provides resistance to FTC and 3TC, it can concurrently lead to an increased susceptibility to TDF, stavudine, and azidothymidine (AZT), and can slow the resistance development against these NRTIs. 2019 Communications biology Introduction HIV M184V 6 11 NRTI 203 208 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Major mutations produce drug resistance by three general molecular mechanisms: mutations of residues in the inhibitor binding site can directly alter PR-PI interactions; some distal mutations confer drug resistance by altering dimerization via changes in inter-subunit interactions; and other distal mutations, such as L76V, can destabilize the dimer and decrease PI potency by creating structural rearrangements in key locations of the protease. 2020 The FEBS journal Introduction HIV L76V 319 323 PR;PI;PI;PR 437;153;364;150 445;155;366;152 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Mutation N83D is classified solely as a major resistance mutation for TPV. 2020 The FEBS journal Introduction HIV N83D 9 13 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Two mutations in PRS5B have a major association with drug-resistance (M46L and I84V), while nine are classified as minor drug resistance mutations (L10I, V11I, M36I, I54V, I62V, I63P, I64V, A71V, and G73T). 2020 The FEBS journal Introduction HIV A71V;G73T;I54V;I62V;I63P;I64V;I84V;L10I;M36I;M46L;V11I 190;200;166;172;178;184;79;148;160;70;154 194;204;170;176;182;188;83;152;164;75;158 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). In addition, we report high percentages of one NRTI (M184V/I) and three NNRTI (K103N/S, Y181C/I and G190A/S) mutations in ART-naive and ART-treated individuals, which confer high-level resistance to 3TC, EFV and/or NVP. 2020 EClinicalMedicine Introduction HIV G190A;G190S;K103N;K103S;M184I;M184V;Y181C;Y181I 100;100;79;79;53;53;88;88 107;107;86;86;60;60;95;95 NNRTI;NRTI 72;47 77;51 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. 3TC monotherapy is also associated with better short-term outcomes than complete treatment interruption amongst PLHIV with M184V 11. 2020 HIV medicine Introduction HIV M184V 123 128 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. However, although there are some small case series 16, evidence is lacking for a protective effect of the M184V mutation from large cohort studies. 2020 HIV medicine Introduction HIV M184V 106 111 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. However, there has been a history of continuing 3TC/FTC in antiretroviral therapy (ART) regimens for some PLHIV with M184V/I because of the potential benefits of maintaining this mutation 5, 6 linked to impaired viral fitness and the finding that 3TC seems to retain some antiviral effect even in the presence of the M184V mutation 7. 2020 HIV medicine Introduction HIV M184I;M184V;M184V 117;117;317 124;124;322 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. One small randomized trial found that continuation of 3TC in PLHIV failing a 3TC-containing regimen was not associated with any difference in change in viral load (VL) or CD4 cell count, but that continued presence of the M184V mutation was associated with a reduced rate of change of the viral sequence 12. 2020 HIV medicine Introduction HIV M184V 222 227 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. One study found that boosted protease inhibitor (bPI) plus 3TC dual maintenance therapy for virally suppressed PLHIV with M184V at prior failure demonstrated an acceptably low failure rate at 48 weeks (3.0%), whereas bPI monotherapy did not (failure rate 24.8%) 8. 2020 HIV medicine Introduction HIV M184V 122 127 PR 29 37 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The HIV-1 reverse transcriptase M184V/I mutation has historically been common in people living with HIV (PLHIV) experiencing virological failure on regimens that contain lamivudine (3TC) or emtricitabine (FTC). 2020 HIV medicine Introduction HIV M184I;M184V 32;32 39;39 RT 10 31 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The question of whether there is a benefit of maintaining 3TC/FTC in PLHIV with the M184V/I mutation remains relevant, particularly as there is current interest in dual-therapy regimens (including some containing 3TC/FTC). 2020 HIV medicine Introduction HIV M184I;M184V 84;84 91;91 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. There is also some in vitro evidence that M184V is associated with higher replication fidelity 13 and may delay or prevent the emergence of resistance to other ART drugs 14, 15. 2020 HIV medicine Introduction HIV M184V 42 47 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Through the analysis of UK HIV cohort data, we aimed to investigate whether 3TC/FTC use demonstrates any association with viral suppression or the occurrence of additional major drug resistance mutations (DRMs) following the detection of the M184V/I mutation. 2020 HIV medicine Introduction HIV M184I;M184V 242;242 249;249 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Furthermore, the Q4R substitution significantly restored interaction of the RGDA/Q112D virus with CPSF6, as shown by decreased resistance of the RGDA/Q112D virus to the inhibitory effect of a truncated form of CPSF6, CSPF6-358. 2020 AIDS research and human retroviruses Introduction HIV Q112D;Q112D;Q4R 81;150;17 86;155;20 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Furthermore, we were able to demonstrate that one SIVcpz strain, which possesses both the Q4R and Q112E substitutions, requires both substitutions to maintain CA-CPSF6-358 interaction. 2020 AIDS research and human retroviruses Introduction HIV Q112E;Q4R 98;90 103;93 Capsid 159 161 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Importantly, either the single or double mutation was sufficient to confer IFN-beta resistance to the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Introduction HIV Q112D 107 112 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In the present study, we tested the effect of the CA Q4R substitution on CSPF6 interaction by the wild-type (WT) virus. 2020 AIDS research and human retroviruses Introduction HIV Q4R 53 56 Capsid 50 52 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Nonetheless, it remained unclear how the Q4R substitution modulated CSPF6-358 resistance in the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Introduction HIV Q112D;Q4R 101;41 106;44 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Strikingly, the Q4R substitution decreased CSPF6 interaction by the WT virus, suggesting an opposite effect of this substitution compared with that on the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Introduction HIV Q112D;Q4R 160;16 165;19 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. The binding process includes an interaction with CPSF6 through the CA N-terminal domain (NTD) as well as through the CA C-terminal domain (CTD); specifically, mutations in the respective CA domains, such as N57A or N74D (NTD) or K182R (CTD), have been shown to reduce CPSF6 binding by HIV-1 CA. 2020 AIDS research and human retroviruses Introduction HIV K182R;N57A;N74D 229;207;215 234;211;219 Capsid;Capsid;Capsid;Capsid 67;117;187;291 69;119;189;293 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. The CA proteins of the adapted viruses exhibited either a single change, resulting in a Q4R substitution, or a double mutation, resulting in G94D/G116R substitutions. 2020 AIDS research and human retroviruses Introduction HIV G116R;G94D;Q4R 146;141;88 151;145;91 Capsid 4 6 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. The results suggested that the Q4R substitution permits the formation of a salt bridge between R4 and D112 in the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Introduction HIV Q112D;Q4R 119;31 124;34 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We recently reported that one CA mutant virus, RGDA/Q112D (H87R, A88G, P90D, P93A, and Q112D), is hypersensitive to interferon (IFN)-beta. 2020 AIDS research and human retroviruses Introduction HIV A88G;H87R;P90D;P93A;Q112D;Q112D 65;59;71;77;52;87 69;63;75;81;57;92 Capsid 30 32 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. We found that tenofovir+lamivudine+efavirenz had superior virologic outcomes compared to nevirapine-based regimens, including among ARV-naive or ARV-experienced individuals and those with wild-type virus or PDR; and while the most common NNRTI mutation, K103N, when detected as a single mutation increased virologic failure with nevirapine-based-ART, it did not increase virologic failure with tenofovir+lamivudine+efavirenz. 2020 EClinicalMedicine Introduction HIV K103N 254 259 NNRTI 238 243 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. An exception is Thr138: in HIV-1, E138T potentiates resistance of Q148H-containing viruses. 2020 Science (New York, N.Y.) Introduction HIV E138T;Q148H 34;66 39;71 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. As a start, we analyzed respective side chains in our SIVrcm Q148H/G140S intasome structure. 2020 Science (New York, N.Y.) Introduction HIV G140S;Q148H 67;61 72;66 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Concordantly, reverting Thr138 to Glu decreased DTG and BIC resistance of Q148H/G140S SIVrcm to the levels observed with HIV-1 Q148H/G140S. 2020 Science (New York, N.Y.) Introduction HIV G140S;G140S;Q148H;T138E;Q148H 80;133;74;24;127 85;138;79;37;132 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Further work will be required to unravel long-range interactions involved in boosting INSTI resistance by secondary changes such as E138T and L74M/T97A. 2020 Science (New York, N.Y.) Introduction HIV E138T;L74M;T97A 132;142;147 137;146;151 INSTI 86 91 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. However, in contrast to DTG, analogue 1 was ~80-fold less effective against HIV-1 Q148H/G140S. 2020 Science (New York, N.Y.) Introduction HIV G140S;Q148H 88;82 93;87 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. In particular, Q148H/G140S changes in HIV-1 IN are associated with complete or partial loss of efficacy across the entire drug class. 2020 Science (New York, N.Y.) Introduction HIV G140S;Q148H 21;15 26;20 IN 44 46 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Moreover, T97A/L74M, which increase resistance of Q148H/G140S HIV-1 to second-generation INSTIs, exerted the same effect on SIVrcm. 2020 Science (New York, N.Y.) Introduction HIV G140S;L74M;Q148H;T97A 56;15;50;10 61;19;55;14 INSTI 89 95 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Q148H/G140S changes in IN rendered HIV-1 and SIVrcm significantly resistant to RAL, by a factor of >2000, whereas EC50 values of the second-generation INSTIs BIC and DTG increased similarly ~5- to-8-fold against HIV-1 and 40 to 73-fold against SIVrcm. 2020 Science (New York, N.Y.) Introduction HIV G140S;Q148H 6;0 11;5 INSTI;IN 151;23 157;25 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. This extended network, which may form a proton wire, is expected to reinforce Ser140 as a hydrogen bond donor for its interaction with His148 Ndelta1, explaining why the E138T substitution can enhance the resistance of Q148H/G140S HIV-1. 2020 Science (New York, N.Y.) Introduction HIV E138T;G140S;Q148H 170;225;219 175;230;224 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. To prevent DNA binding to the target binding groove, which would occlude INSTI occupancy, the intasomes were prepared using A119D IN that precludes target DNA capture without affecting IN active site function. 2020 Science (New York, N.Y.) Introduction HIV A119D 124 129 INSTI;IN;IN 73;130;185 78;132;187 32001525 Structural basis of second-generation HIV integrase inhibitor action and viral resistance. To visualize the impact of the Q148H/G140S substitutions on drug binding, we imaged mutant SIVrcm intasomes in complex with BIC to a local resolution of 2.8 A (figs S7-8, S17A, table S1). 2020 Science (New York, N.Y.) Introduction HIV G140S;Q148H;S17A 37;31;171 42;36;175 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. Despite their use, at virologic failure, it appears that TDF/3TC-containing regimens fail with M184V plus K65R whereas AZT-containing regimens fail with the occurrence of Thymidine Analog Mutations (TAMs). 2020 AIDS research and therapy Introduction HIV K65R;M184V 106;95 110;100 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. Furthermore, resistance to NRTIs, NNRTIs, and PIs vary among the different subtypes for example the K65R mutation develops much faster in subtype C than other subtypes. 2020 AIDS research and therapy Introduction HIV K65R 100 104 NNRTI;NRTI;PI 34;27;46 40;32;49 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. A preliminary study on CRF01_AE-infected patients, conducted in China by our research team, found that the frequency of the S68G mutation showed a 5.5% increase in patients who failed treatment. 2020 BMC infectious diseases Introduction HIV S68G 124 128 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Moreover, the S68G mutation demonstrated a close link with the K65R mutation (unpublished data). 2020 BMC infectious diseases Introduction HIV K65R;S68G 63;14 67;18 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The role of the S68G mutation in drug resistance and its relationship with the K65R mutation has yet to be elucidated. 2020 BMC infectious diseases Introduction HIV K65R;S68G 79;16 83;20 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Thus, we conducted this study to: 1) explore the frequency of S68G mutation and K65R/S68G double mutation occurrence among various subtypes of HIV-1 worldwide; 2) ascertain the temporal association of S68G and K65R mutations among patients infected with CRF01_AE who failed treatment; and 3) understand the role of the S68G mutation in susceptibility to NRTI and viral replication when combined with the K65R mutation. 2020 BMC infectious diseases Introduction HIV K65R;K65R;K65R;S68G;S68G;S68G;S68G 80;210;404;62;85;201;319 84;214;408;66;89;205;323 NRTI 354 358 32048186 Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV-1. More important, these compounds still displayed significant inhibitions against T20-resistant HIV-1 strains, pNL4-3gp41(36G)V38E, N42S and pNL4-3gp41(36G)V38A, N42T. 2020 Natural products and bioprospecting Introduction HIV N42S;N42T;V38A;V38E 130;160;153;123 134;164;158;128 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Previous research in Ghana has shown low prevalence (5%) of drug resistance, with some studies reporting no transmitted drug resistance mutations, while others observed only minor mutations L10I, L10 V, V11I, and E35G in 4 patients and V179E in another. 2020 Medicine Introduction HIV E35G;L10I;L10V;V11I;V179E 213;190;196;203;236 217;194;201;207;241 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Two major drug resistance mutations (M184 V and Y181C) in 1 patient and M46L another were observed in the threshold survey. 2020 Medicine Introduction HIV M184V;M46L;Y181C 37;72;48 44;76;53 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. 3TC is also approved as an anti-HIV-1 agent, and M184V in HIV-1 RT, which corresponds to M204V in HBV RT, has also been reported as an amino acid substitution responsible for 3TC resistance in HIV-1. 2020 Scientific reports Introduction HIV M184V 49 54 RT;RT 64;102 66;104 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Accordingly, we assumed that crystallographic studies of HIV-1 RT containing HBV-associated amino acids at the N-site should also provide important clues for understanding the mechanism of 3TC/ETV resistance caused by common M204V/I in HBV RT (M184V/I in HIV-1 RT). 2020 Scientific reports Introduction HIV M184I;M184V 244;244 252;252 RT;RT;RT 63;240;261 65;242;263 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Furthermore, we determined a series of crystal structures for HIV-1 RTF115Y/Y116F/Q151M:DNA in complex with 3TC-triphosphate (3TC-TP) and ETV-triphosphate (ETV-TP), and with their reference natural substrates dCTP and dGTP, respectively. 2020 Scientific reports Introduction HIV F115Y;Q151M;Y116F 70;82;76 75;87;81 RT 68 70 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Here, we report the acquisition of 3TC/ETV resistance using HIV-1 with three HBV-associated amino acid substitutions (F115Y/Y116F/Q151M) in the RT N-site. 2020 Scientific reports Introduction HIV F115Y;Q151M;Y116F 117;130;124 123;135;129 RT 144 146 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. These structures provide a basis for understanding the common structural mechanism of the acquisition of resistance to 3TC and ETV conferred by the M184V/I and should aid in structure-based drug design to develop new agents effective against drug-resistant HBV. 2020 Scientific reports Introduction HIV M184I;M184V 148;148 155;155 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We recently reported that the HBV-associated Q151M mutation alone in HIV-1 RT renders HIV-1 highly sensitive to ETV, and we determined the crystal structure of HIV-1 RTQ151M:DNA complexed with ETV-triphosphate (ETV-TP). 2020 Scientific reports Introduction HIV Q151M;Q151M 168;45 173;50 RT;RT 75;166 77;168 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. For example, V90I and V179E occurred more frequently after treatment with etravirine (ETR) and rilpivirine (RPV) in non-B HIV-1 compared to subtype B HIV-1. 2020 BMC infectious diseases Introduction HIV V179E;V90I 22;13 27;17 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. A good example is G118R in integrase, a polymorphism that confers significant integrase strand transfer inhibitor (INSTI) resistance. 2020 The Journal of antimicrobial chemotherapy Introduction HIV G118R 18 23 IN;IN;INSTI 27;78;115 36;87;120 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. A recent report suggested that methionine at residue 74 was in closer proximity to T97 and F121 as compared with leucine at position 74 in a modelled subtype C integrase and, of note, L74F was found to contribute to high-level dolutegravir resistance when combined with major mutations G140S and Q148H. 2020 The Journal of antimicrobial chemotherapy Introduction HIV G140S;L74F;Q148H 286;184;296 291;188;301 IN 160 169 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. All three had L74I in integrase at both baseline and at VF. 2020 The Journal of antimicrobial chemotherapy Introduction HIV L74I 14 18 IN 22 31 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. At VF the major integrase mutation Q148R occurred in two and G140R in one. 2020 The Journal of antimicrobial chemotherapy Introduction HIV G140R;Q148R 61;35 66;40 IN 16 25 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. In the Stanford Resistance Database (https://hivdb.stanford.edu) L74I is reported to be observed in 3%-20%, depending on subtype. 2020 The Journal of antimicrobial chemotherapy Introduction HIV L74I 63 69 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L74I and L74M are assessed together and combined prevalences are often reported as they have both been shown to enhance integrase inhibitor resistance when present with major INSTI mutations. 2020 The Journal of antimicrobial chemotherapy Introduction HIV L74M;L74I 9;0 13;4 IN;INSTI 120;175 129;180 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The L74M variant has been included as a minor mutation for the first-generation INSTI raltegravir in the IAS-USA drug resistance mutations list (https://www.iasusa.org/wp-content/uploads/2019/09/27-3-111.pdf), but the L74I variant is not recognized as a resistance-associated mutation. 2020 The Journal of antimicrobial chemotherapy Introduction HIV L74I;L74M 218;4 222;8 INSTI 80 85 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The Stanford Resistance Database includes L74I in combination with other integrase mutations. 2020 The Journal of antimicrobial chemotherapy Introduction HIV L74I 42 46 IN 73 82 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. We aimed to determine the prevalence of INSTI resistance, as well as the prevalence and dynamics of L74I, in this setting. 2020 The Journal of antimicrobial chemotherapy Introduction HIV L74I 100 104 INSTI 40 45 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. The most promising compound DB02 exhibited potent anti-HIV-1 activity against laboratory adapted strains and primary isolated strains (EC50s (concentrations inhibiting virus replication by 50%) range from 2.40 to 41.8 nmol/L), along with an improved sensitivity against K103N or Y181C than S-DABOs26. 2020 Acta pharmaceutica Sinica. B Introduction HIV K103N;Y181C 270;279 275;284 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. We also observed differential uncoating kinetics for the mutant N74D in a HeLa cell line engineered to express TRIM-CypA. 2020 Virology journal Introduction HIV N74D 64 68 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. We found that the E45A and N74D mutations uncoated slower than wildtype virus, while the mutation A92E uncoated faster than wildtype in OMK cells. 2020 Virology journal Introduction HIV A92E;E45A;N74D 98;18;27 102;22;31 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Across those clinical isolates (no subtype information was provided), DOR displayed a good antiviral activity with fold changes in EC50<9 against most single mutant viruses, including A98G, E138A/G/K/Q, G190A, K101E/P, K103N/S, L100I, P236L, V106M, V108I, V197D, V90I, Y181C/V, and Y188H/C. 2020 Drugs in context Introduction HIV A98G;E138A;E138G;E138K;E138Q;G190A;K101E;K101P;K103N;K103S;L100I;P236L;V106M;V108I;V197D;V90I;Y181C;Y181V;Y188C;Y188H 184;190;190;190;190;203;210;210;219;219;228;235;242;249;256;263;269;269;282;282 188;201;201;201;201;208;217;217;226;226;233;240;247;254;261;267;276;276;289;289 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Another substitution, K101E, was detected in one patient who had a virological failure in a phase II DOR dose-ranging study, although the virus bearing this mutation did not confer significant resistance against DOR in vitro. 2020 Drugs in context Introduction HIV K101E 22 27 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Both second-generation inhibitors were selected for their retained antiretroviral activity against a single K103N substitution. 2020 Drugs in context Introduction HIV K103N 108 113 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. DOR exhibited <3-fold change in EC50 against K103N, Y181C, or double mutant K103N/Y181C strains. 2020 Drugs in context Introduction HIV K103N;K103N;Y181C;Y181C 45;76;52;82 50;81;57;87 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. F227C or Y318F alone may be linked to clinical resistance against DOR. 2020 Drugs in context Introduction HIV Y318F;F227C 9;0 14;5 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Finally, substitutions that disrupt the NNRTI-binding pocket, such as Y188L and M230L, confer pan-resistance against all NNRTIs. 2020 Drugs in context Introduction HIV M230L;Y188L 80;70 85;75 NNRTI;NNRTI 40;121 45;127 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Importantly, preliminary clinical data obtained from a small number of participants (n=9) indicated that DOR could be used efficaciously to suppress viral replication for 96 weeks in individuals infected with K103N or G190A viruses. 2020 Drugs in context Introduction HIV G190A;K103N 218;209 223;214 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. In almost all cases, DOR selected first for V106A/M substitutions. 2020 Drugs in context Introduction HIV V106A;V106M 44;44 51;51 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. It is thus possible that the F227L substitution per se may confer only low-level resistance against DOR. 2020 Drugs in context Introduction HIV F227L 29 34 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Most importantly, DOR was active against the most prevalent NNRTI-resistance mutations K103N, Y181C, and G190A. 2020 Drugs in context Introduction HIV G190A;K103N;Y181C 105;87;94 110;92;99 NNRTI 60 65 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Mutations that emerged secondary to V106A/M included F227L/C/V or L234I. 2020 Drugs in context Introduction HIV F227C;F227L;F227V;L234I;V106A;V106M 53;53;53;66;36;36 62;62;62;71;43;43 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Notably, resistance against DOR was most commonly diagnosed with several concomitant substitutions, whereas unique K103N substitutions were found in half of the participants who had mutations in the EFV arm of the DRIVE-AHEAD trial, which may suggest that the dynamics of DOR resistance mutations in vivo seem to be more diverse and complicated than expected. 2020 Drugs in context Introduction HIV K103N 115 120 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Of note, the viral breakthroughs described earlier were observed when selections were made with 3x EC95 of DOR; however, at 10x EC95, only F227C was selected. 2020 Drugs in context Introduction HIV F227C 139 144 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Other in vitro studies confirmed that viruses bearing both V106A and F227L substitutions reduced DOR susceptibility >500-fold. 2020 Drugs in context Introduction HIV F227L;V106A 69;59 74;64 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Other single substitutions including G190E/S, V106A, Y188L, and M230L reduced DOR susceptibility >10-fold. 2020 Drugs in context Introduction HIV G190E;G190S;M230L;V106A;Y188L 37;37;64;46;53 44;44;69;51;58 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Other substitutions such as V106M, V108I, V179D, Y188H, or P236L conferred less than 10-FC against DOR. 2020 Drugs in context Introduction HIV P236L;V106M;V108I;V179D;Y188H 59;28;35;42;49 64;33;40;47;54 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Other substitutions such as Y181C (NVP) or G190A (NVP, EFV) display various degrees of cross resistance against different NNRTIs, regardless of their novelty. 2020 Drugs in context Introduction HIV G190A;Y181C 43;28 48;33 NNRTI 122 128 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Resistance to previous NNRTIs is heterogeneous, with resistance against first-generation NNRTIs (NVP and EFV) being often associated with the highly fit K103N substitution, whereas resistance against second-generation NNRTIs (ETR and RPV) is often linked to substitutions at position E138 together with the M184I NRTI-resistance substitution. 2020 Drugs in context Introduction HIV K103N;M184I 153;307 158;312 NNRTI;NNRTI;NNRTI;NRTI 23;89;218;313 29;95;224;317 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Since DOR and ISL belong to two different drug classes and given that F227C increases the in vitro susceptibility of HIV-1 to ISL, this combination is expected to provide a combined high genetic barrier against the development of resistance. 2020 Drugs in context Introduction HIV F227C 70 75 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Supporting phenotypic testing, when DOR selections were initiated with K103N, Y181C, or K103N/Y181C viruses, they did not lead to the development of further RT mutations, an observation that may justify the use of DOR against these substitutions. 2020 Drugs in context Introduction HIV K103N;K103N;Y181C;Y181C 71;88;78;94 76;93;83;99 RT 157 159 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. The double mutant viruses V106A/L234I (subtype B) and V108I/L234I (subtype A) eventually acquired a third mutation to give triple mutant viruses V106A/L234I/F227L (subtype B) and V108I/L234I/V106A(I) that both conferred over 150-fold decreases in DOR susceptibility. 2020 Drugs in context Introduction HIV F227L;L234I;L234I;V106A;V106A;V108I;L234I;L234I;V106A;V108I 157;151;185;145;191;179;32;60;26;54 162;156;190;150;196;184;37;65;31;59 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. The G190S, Y188L, and M230L substitutions confer >95-fold resistance. 2020 Drugs in context Introduction HIV G190S;M230L;Y188L 4;22;11 9;27;16 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. The highest levels of reduction in DOR susceptibility were associated with V106A or Y188L or each of these two mutations in combination with at least one secondary mutation, such as V106A/G190A/F227L, Y188L/K103N, Y188L/V106I, and E138K/Y181C/M230L. 2020 Drugs in context Introduction HIV E138K;F227L;G190A;M230L;V106A;Y181C;K103N;V106A;V106I;Y188L;Y188L;Y188L 231;194;188;243;182;237;207;75;220;84;201;214 236;199;193;248;187;242;212;80;225;89;206;219 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. These cell-based observations are in agreement with biochemical assays that showed that DOR exhibits potent inhibitory activity against wild-type, K103N, and Y181C recombinant reverse transcriptase enzymes with half-inhibitory concentrations (IC50s) of 12.2, 9.7, and 9.7 nM, respectively. 2020 Drugs in context Introduction HIV K103N;Y181C 147;158 152;163 RT 176 197 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. V106A is a non-polymorphic substitution selected by NVP, while V106M is commonly selected by both NVP and EFV from subtype C viruses. 2020 Drugs in context Introduction HIV V106M;V106A 63;0 68;5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. M184V is the most commonly occurring NRTI ADR mutation. 2020 Virology journal Introduction HIV M184V 0 5 NRTI 37 41 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. The next most common ADR mutation is the K103N mutation (associated with non-nucleoside reverse transcriptase inhibitors; NNRTIs) which cause high-level resistance to nevirapine (NVP) and variable resistance to efavirenz (EFV). 2020 Virology journal Introduction HIV K103N 41 46 NNRTI;NNRTI 73;122 109;128 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Depletion of TRIM5alphahu expression in Jurkat and CD4+ T cells rescued HIV-1 infection of viruses that cannot interact with CypA, such as HIV-1-P90A. 2020 Cell reports Introduction HIV P90A 145 149 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. In agreement with our hypothesis that CypA protects the core from TRIM5alphahu, infection of PBMCs and CD4+ T cells by HIV-1-A92E viruses was insensitive to the disruption of CypA-capsid interactions. 2020 Cell reports Introduction HIV A92E 125 129 Capsid 180 186 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Infection of HIV-1-A92E/G94D viruses was not affected by disruption of CypA-capsid interactions, which correlates with the loss of TRIM5alphahu binding to HIV-1 cores bearing the A92E/G94D mutation. 2020 Cell reports Introduction HIV A92E;G94D;G94D;A92E 179;24;184;19 183;28;188;23 Capsid 76 82 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Interestingly, TRIM5alphahu does not bind to HIV-1 cores bearing the capsid mutant A92E (HIV-1-A92E) or G94D (HIV-1-G94D). 2020 Cell reports Introduction HIV A92E;G94D;A92E;G94D 83;104;95;116 87;108;99;120 Capsid 69 75 32192810 Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity. In earlier work, we previously reported an HIV-1 V1V2 sequence variant K155M (HxB2 numbering, hereafter referred to as K-M) located in the conserved V1 beta-strand of the V1V2 beta-barrel that alters V1V2 antigenicity. 2020 Vaccine Introduction HIV K155M 71 76 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. In this study, we have further improved the OLA-Simple assay in two areas: validated probes for detection of K65R - a major resistance mutation to tenofovir, which is an NRTI widely used with NNRTIs or dolutegravir, and exploited an in-house software program to automatically quantify signal and classify results from lateral flow tests. 2020 AIDS (London, England) Introduction HIV K65R 109 113 NNRTI;NRTI 192;170 198;174 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. Moreover, an OLA-Simple kit that detects the NRTI mutation M184V and NNRTI mutations K103N, Y181C, and G190A was clinically validated across multiple HIV-1 subtypes, showing 99.6% sensitivity and 98.2% specificity compared to Sanger sequencing. 2020 AIDS (London, England) Introduction HIV G190A;K103N;M184V;Y181C 103;85;59;92 108;90;64;97 NNRTI;NRTI 69;45 74;49 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. G40E and G40R are among several single missense mutations in the elbow region of both the monomers of the HIV-1 protease, which results in the production of non-infectious virus particles due to decrease in the protease activity upon substitution. 2020 Scientific reports Introduction HIV G40R;G40E 9;0 13;4 PR;PR 112;211 120;219 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Thus, the single mutations (G40E and G40R) in both the monomers cause the protease dimer to be relatively rigidified. 2020 Scientific reports Introduction HIV G40E;G40R 28;37 33;41 PR 74 82 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. We, therefore considered the mutants of HIV-1 protease (G40E and G40R) based on these experimental mutational data and subjected them to MD simulations to examine the effect of mutations on the flexibility of the protease. 2020 Scientific reports Introduction HIV G40E;G40R 56;65 61;69 PR;PR 46;213 54;221 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Further, both the HIV-1 P90A capsid mutant and the HIV-1 N74D capsid mutant, referred to hereafter as P90A and N74D respectively, have been shown to be hypersensitive to the effects of IFN, suggesting that one or more IFN-induced restriction factors block infection of these capsid mutant viruses. 2020 PLoS pathogens Introduction HIV N74D;P90A 111;102 115;106 Capsid;Capsid;Capsid 29;62;275 35;68;281 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Further, we find that TRIM34 requires TRIM5alpha to inhibit N74D while inhibition of P90A occurs independent of TRIM34. 2020 PLoS pathogens Introduction HIV N74D;P90A 60;85 64;89 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Here we use this approach to identify capsid-targeting restrictions that target the P90A and N74D HIV-1 capsid mutants. 2020 PLoS pathogens Introduction HIV N74D;P90A 93;84 97;88 Capsid;Capsid 38;104 44;110 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Single amino acid mutations in the HIV-1 capsid protein, for example N74D for CPSF6 and P90A for CypA, abrogate binding to these host factors. 2020 PLoS pathogens Introduction HIV N74D;P90A 69;88 73;92 Capsid 41 47 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. While the CypA-binding deficient P90A mutant becomes more sensitive to TRIM5alpha restriction, the CPSF6-binding deficient N74D mutant becomes sensitive to a novel restriction by the TRIM5alpha paralog, TRIM34. 2020 PLoS pathogens Introduction HIV N74D;P90A 123;33 127;37 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. The DetMDRs also contain previously identified non-polymorphic accessory mutations L10V/G, V11I, I13V, K20T/R, L33F/I/M, K43T, F53L, A71L, T74P, and L89V. 2014 Discoveries (Craiova, Romania) Introduction HIV A71L;F53L;I13V;K20R;K20T;K43T;L10G;L10V;L33F;L33I;L33M;L89V;T74P;V11I 133;127;97;103;103;121;83;83;111;111;111;149;139;91 137;131;101;109;109;125;89;89;119;119;119;153;143;95 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. The DetMDRs differ from isolates previously studied by our group in that these contain the major drug resistance mutations L33F, I47V, I50V, I54M, L76V, V82I/F, and I84F not present in the previous cohort (Table 1). 2014 Discoveries (Craiova, Romania) Introduction HIV I47V;I50V;I54M;I84F;L33F;L76V;V82F;V82I 129;135;141;165;123;147;153;153 133;139;145;169;127;151;159;159 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. These studies provide insight into the structural changes that lead to multidrug resistance; in particular, we identify previously unreported roles for the I47V, V32I, I54M, L90M mutations in protease flap dynamics (Figure 1). 2014 Discoveries (Craiova, Romania) Introduction HIV I47V;I54M;L90M;V32I 156;168;174;162 160;172;178;166 PR 192 200 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Additionally, V179D/E mutation distributed in 26 networks, suggesting that several independent CRF01_AE strains with V179D/E were involved in ongoing transmission in Shanghai. 2020 BMC infectious diseases Introduction HIV V179D;V179D;V179E;V179E 14;117;14;117 21;124;21;124 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. For example, most of the HIV-1 O group viruses are considered to be naturally resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) due to the presence of the Y181C mutation. 2020 BMC infectious diseases Introduction HIV Y181C 174 179 NNRTI;NNRTI 91;139 126;145 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. However, the combination of V179D and K103R acts synergistically to reduce EFV and NVP susceptibility by about 10- to 15-fold, leading to intermediate resistance to EFV and NVP. 2020 BMC infectious diseases Introduction HIV K103R;V179D 38;28 43;33 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. K103R is also a polymorphic mutation and, alone, has no effect on reduction in phenotypic susceptibility to NNRTIs. 2020 BMC infectious diseases Introduction HIV K103R 0 5 NNRTI 108 114 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. reported that CRF01_AE subtype-related resistance to fostemsavir, an attachment inhibitor, appeared to be associated with the natural presence of substitutions S375H and M475I. 2020 BMC infectious diseases Introduction HIV M475I;S375H 170;160 175;165 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. reported that the proportion of V179D/E among Shanghai CRF01_AE was 7.1%, which was higher than all other China CRF01_AE. 2020 BMC infectious diseases Introduction HIV V179D;V179E 32;32 39;39 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Selective acquisition of G190S, which causes higher levels of EFV and NVP resistance than K103N, in HIV-1 subtype A from Russia is another example of a distinct genetic barrier to resistance among different subtypes. 2020 BMC infectious diseases Introduction HIV G190S;K103N 25;90 30;95 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. The V106M mutation, which confers high-level resistance to efavirenz (EFV) and nevirapine (NVP), is preferentially selected by EFV in subtype C viruses compared with subtype B viruses. 2020 BMC infectious diseases Introduction HIV V106M 4 9 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. This observation suggested that the high prevalence of V179D/E was a concern. 2020 BMC infectious diseases Introduction HIV V179D;V179E 55;55 62;62 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. V179D is a common polymorphic mutation that scored by the Stanford HIV Drug Resistance Database as conferring potential low-level resistance to NNRTIs including EFV, NVP, etravirine (ETR), and rilpivirine (RPV). 2020 BMC infectious diseases Introduction HIV V179D 0 5 NNRTI 144 150 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. V179D mutation occurred most frequently in CRF01_AE and subtype F isolates, with a rate of 1.7 and 4.1%, respectively. 2020 BMC infectious diseases Introduction HIV V179D 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Genetic resistance pathways including primary mutations at codons Y143C/H/R, Q148H/K/R or N155H together with one or more additional associated secondary mutations at L74M, E92Q, T97A, E138E/A/K or G140S/A, has been reported to result in higher levels of resistance with RAL treatment. 2020 PloS one Introduction HIV E138A;E138E;E138K;E92Q;G140A;G140S;L74M;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143H;Y143R 185;185;185;173;198;198;167;90;77;77;77;179;66;66;66 194;194;194;177;205;205;171;95;86;86;86;183;75;75;75 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. On its own, the Y143R non-polymorphic mutation reduces RAL susceptibility by ~20-fold, but has no effect on DTG susceptibility. 2020 PloS one Introduction HIV Y143R 16 21 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. On the other hand, EVG specific resistance pathways involve IN mutations T66I/A/K, E92Q/G and S147G pathways. 2020 PloS one Introduction HIV E92G;E92Q;S147G;T66A;T66I;T66K 83;83;94;73;73;73 89;89;99;81;81;81 IN 60 62 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The E92Q mutation alone reduces EVG susceptibility to >20-fold and results in limited (<5-fold) cross-resistance to RAL. 2020 PloS one Introduction HIV E92Q 4 8 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The E92Q mutation is also selected in vitro by DTG and reduces DTG susceptibility by ~1.5-fold. 2020 PloS one Introduction HIV E92Q 4 8 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Additionally, we evaluate the effect of this single Q563R substitution on Env conformation and recognition by MPER-targeted bNAbs. 2020 PLoS pathogens Introduction HIV Q563R 52 57 Env 74 77 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Here we demonstrate that the Q563R change reduces HIV-1 infectivity by disrupting viral membrane fusion, and that Envs harboring this alteration are dependent on gp41-targeted antibodies to overcome this viral defect. 2020 PLoS pathogens Introduction HIV Q563R 29 34 gp41;Env 162;114 166;118 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. In the course of characterizing the longitudinal evolution of Env in a subject exhibiting a broadly neutralizing antibody response to HIV-1, we have identified a naturally occurring Env variant containing a Q563R change in gp41. 2020 PLoS pathogens Introduction HIV Q563R 207 212 gp41;Env;Env 223;62;182 227;65;185 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Notably, the amino acid residue glutamine (Q) at position 563 (HXB2 numbering) in HR1 interacts with isoleucine (I) at positions 642 and 646 of HR2. 2020 PLoS pathogens Introduction HIV I642I;Q563Q 98;29 135;64 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Previous reports also show that changing Q563 to alanine (Q563A) modestly reduces viral fusion, whereas alteration to arginine (Q563R) causes a dramatic loss of infectivity. 2020 PLoS pathogens Introduction HIV Q563A;Q563R 58;128 63;133 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). In said study, 265 virologically suppressed participants- 96% of whom had a historical genotype detecting the M184V mutation- were randomized to either boosted protease inhibitor monotherapy or to lamivudine plus boosted protease inhibitor. 2020 EBioMedicine Introduction HIV M184V 110 115 PR;PR 160;221 168;229 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). This is the first clinical trial specifically designed to address the efficacy of lamivudine and dolutegravir as dual therapy for maintenance of viral suppression in patients with historical lamivudine resistance as long as M184V/I and/or K65R/E/N mutations are not found on proviral DNA population sequencing prior to dual therapy initiation. 2020 EBioMedicine Introduction HIV K65E;K65N;K65R;M184I;M184V 239;239;239;224;224 247;247;247;231;231 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Although they could effectively inhibit most of the RT-resistant mutations caused by the first-generation NNRTIs, they generally failed to suppress the most refractory mutations E138K and RES056 (K103N + Y181C). 2020 Acta pharmaceutica Sinica. B Introduction HIV E138K;K103N;Y181C 178;196;204 183;202;209 NNRTI;RT 106;52 112;54 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. K103N and Y181C are the two most prevalent mutations in vivo, which elicited frequently resistance to NVP and EFV. 2020 Acta pharmaceutica Sinica. B Introduction HIV Y181C;K103N 10;0 15;5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. Patients failing an NNRTI-based first-line regimen with genotypic drug resistance mutations typically present with M184V/I, K65R, and/or thymidine analogue mutations (TAMs) and K103N, V106M/A and/or Y181C as the most prevalent NRTI and NNRTI mutations, respectively. 2020 PloS one Introduction HIV K103N;K65R;M184I;M184V;V106A;V106M;Y181C 177;124;115;115;184;184;199 182;128;122;122;191;191;204 NNRTI;NNRTI;NRTI 20;236;227 25;241;231 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. Re-suppression has been observed in patients with major genotypic drug resistance mutations particularly those failing an NNRTI-based first-line regimen with M184V and K103N. 2020 PloS one Introduction HIV K103N;M184V 168;158 173;163 NNRTI 122 127 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. Here, we describe a case of pretreatment resistance in a patient newly diagnosed with HIV-1-infection found to have the accessory S230R mutation before initiating DTG, emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF). 2020 Medicine Introduction HIV S230R 130 135 HIV infections 86 101 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. Samples from untreated individuals from sub-Saharan Africa revealed a 2.4% prevalence of major INSTI associated mutations (including S230R), all detected at a frequency threshold <20%. 2020 Medicine Introduction HIV S230R 133 138 INSTI 95 100 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. In vitro selection experiments indicated that substitutions in the 74 position combined with major mutations (G140A/C/S, Q148 H/K/R) and other accessory mutations (V75I, T97A) can significantly reduce susceptibility to INSTI, whereas this mutation alone has minimal impact on INSTI susceptibility or HIV-1 replication capacity. 2020 Viruses Introduction HIV G140A;G140C;G140S;Q148H;Q148K;T97A;V75I 110;110;110;121;121;170;164 119;119;119;131;131;174;168 INSTI;INSTI 219;276 224;281 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Interestingly, these patients were all from Russia and had an HIV infection with subtype A and the L74I mutation before the treatment initiation. 2020 Viruses Introduction HIV L74I 99 103 HIV infections 62 75 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The efficacy outcomes in this study were similar to those of the ATLAS study, which had 2 treatment experience participants with the L74I mutation from the Russian Federation with virological failure after therapy containing CAB. 2020 Viruses Introduction HIV L74I 133 137 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The L74I mutation is located in the catalytic core domain and is part of the hydrophobic cluster including L63, T97, F100/Y100, L101, L113/I113, and F121 near the active site of integrase. 2020 Viruses Introduction HIV L74I 4 8 IN 178 187 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The L74I substitution in integrase has been described as a polymorphic mutation in a low but substantial proportion (21%) of subtype A sequences; however, according to previous studies in Russia and the former Soviet Union (FSU) countries, the prevalence of this mutation varied from 93% to 100%. 2020 Viruses Introduction HIV L74I 4 8 IN 25 34 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. In that study, we did not identify any potential compensatory mutations that allowed for regain of function in the presence of the H196Q variant leading to this variant being only fleetingly detected and eventually replaced by escape mutations with less significant impacts on important Nef functions. 2020 PloS one Introduction HIV H196Q 131 136 Nef 287 290 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Not surprisingly, the H196Q variant selectively disrupted Nef functions that rely on interactions with AP-2, such as downregulation of tetherin, CD4, and CD28 and disrupted Nef's ability to reduce SERINC5-mediated reductions of viral infectivity, while having no impact on MHC-I downregulation, a function that does not rely on AP-2 interactions. 2020 PloS one Introduction HIV H196Q 22 27 Nef;Nef 58;173 61;176 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Though selection eventually favored changes of the first position in MW9, specifically M195I or M195V, an H196Q (second position in MW9) substitution was initially favored in several animals. 2020 PloS one Introduction HIV H196Q;M195I;M195V 106;87;96 111;92;101 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Although previous studies have focused on the Cys-rich domain of Tat in HIV-1 and SIV, the effect of Y44A substitution in the first domain of HIV-2 Tat remains to be elucidated. 2020 International journal of molecular sciences Introduction HIV Y44A 101 105 Tat;Tat 65;148 68;151 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Among them, we found that Y44A mutation completely inactivated HIV-2 Tat. 2020 International journal of molecular sciences Introduction HIV Y44A 26 30 Tat 69 72 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Here, we present a sequence- and structure-based mutation analysis supported by in vitro characterization of the Y44A mutant HIV-2 Tat protein. 2020 International journal of molecular sciences Introduction HIV Y44A 113 117 Tat 131 134 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. It was previously reported that the transcription activation function of HIV-1 Tat can be abolished upon Y26A and SIV (simian immunodeficiency virus) Tat by Y55A amino acid substitutions. 2020 International journal of molecular sciences Introduction HIV Y26A;Y55A 105;157 109;161 Tat;Tat 79;150 82;153 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. On a similar note, Y55A mutation in the Cys-rich domain of SIV Tat protein was also reported to inactivate the protein. 2020 International journal of molecular sciences Introduction HIV Y55A 19 23 Tat 63 66 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The effects of protein inactivation on viral capsid production, RT activity, and transduction efficiency were compared to those of the wild-type and Y55A mutant proteins. 2020 International journal of molecular sciences Introduction HIV Y55A 149 153 Capsid;RT 45;64 51;66 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The results of our study indicate that Y44A mutation in the N-terminal Pro-rich domain severely limits the transactivation function of HIV-2 Tat protein. 2020 International journal of molecular sciences Introduction HIV Y44A 39 43 Tat 141 144 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. While wild-type Tat stimulates the activity of RT, Nullbasic Tat mutations; where the entire basic domain is replaced by Gly and Ala residues, and Y47D substitution, were found to hinder Tat-mediated transactivation, extinguish reverse transcription, and inhibit the activity of Rev. 2020 International journal of molecular sciences Introduction HIV Y47D 147 151 RT;Rev;Tat;Tat;Tat;RT 228;279;16;61;187;47 249;282;19;64;190;49 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Although RT E138K was observed as with the other subtypes, it was followed by RT K101E to yield the unique double substitution RT E138K/K101E instead of E138K/L100I. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K;E138K;E138K;K101E;K101E;L100I 12;130;153;81;136;159 17;135;158;86;141;164 RT;RT;RT 9;78;127 11;80;129 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Among these, only the RT Y188L substitution was shown to confer high-level (>100-fold change) DOR resistance. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV Y188L 25 30 RT 22 24 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. By contrast, under the same conditions, RT substitutions L100I and K103N were the major substitutions associated with EFV, and E138K and K101P substitutions were the 2 most common resistance pathways in selection studies with RPV. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K;K101P;K103N;L100I 127;137;67;57 132;142;72;62 RT 40 42 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. DOR was rationally designed to address limitations associated with other approved NNRTIs, such as resistance from common NNRTI resistance-associated substitutions in reverse transcriptase (RT), eg, K103N, Y181C, and G190A, the central nervous system (CNS) toxicity observed with efavirenz (EFV), and the food requirement and high baseline viral load exclusion associated with rilpivirine (RPV). 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV G190A;K103N;Y181C 216;198;205 221;203;210 RT;NNRTI;NNRTI;RT 166;82;121;189 187;88;126;191 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Eight participants had the RT K103N substitution, and 2 participants had the RT G190A substitution. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV G190A;K103N 80;30 85;35 RT;RT 27;77 29;79 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Furthermore, DOR shows >5-fold more potent activity than RPV against viruses with the RT Y181C substitution in the presence of 100% normal human serum. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV Y181C 89 94 RT 86 88 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. In vitro studies have shown that DOR has >50-fold improved potency compared with EFV against viruses with the RT K103N substitution. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K103N 113 118 RT 110 112 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. No viral breakthrough was observed with DOR for any mutant, whereas breakthrough viruses were readily detected with RPV against RT Y181C, K103N/Y181C, and E138K mutants and with EFV against RT K103N and K103N/Y181C containing variants. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K;K103N;K103N;K103N;Y181C;Y181C;Y181C 155;138;193;203;131;144;209 160;143;198;208;136;149;214 RT;RT 128;190 130;192 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Resistance selections were conducted with the K103N, Y181C, G190A, E138K, and K103N/Y181C mutant viruses using clinically relevant concentrations of DOR, RPV, and EFV. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K;G190A;K103N;K103N;Y181C;Y181C 67;60;46;78;53;84 72;65;51;83;58;89 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Results with subtype A virus were similar to those observed with subtype B; the major resistance pathway started with the development of the RT V106A mutant at a lower DOR concentration, followed by the RT F227L mutant as DOR concentrations increased. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV F227L;V106A 206;144 211;149 RT;RT 141;203 143;205 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. The development of resistance was characterized by the selection of RT mutants with the V106A substitution, followed by the emergence of substitutions of F227L or L234I with escalating DOR concentrations. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV F227L;L234I;V106A 154;163;88 159;168;93 RT 68 70 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. The IQ values against RT substitutions K103N, Y181C, and K103N/Y181C mutants were 39, 27, and 25, respectively, for DOR, whereas RPV displayed IQ values of 4.6, 1.4, and 0.8, respectively, and EFV showed IQ values of 2.5, 60, and 1.9, respectively. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K103N;K103N;Y181C;Y181C 39;57;46;63 44;62;51;68 RT 22 24 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. The RT Y188L substitution is uncommon among patients for whom NNRTI therapy has failed, possibly because it requires 2 base changes (TTA [tyrosine] to TTA [leucine] or CTT [leucine]) and is associated with low viral replication capacity. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV Y188L 7 12 NNRTI;RT 62;4 67;6 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. The V106A, V106A/L234I, and V106A/L234I/V108I resistance-associated substitutions, which demonstrated 10-fold (single substitution) and >150-fold (double and triple substitutions) resistance to DOR, were susceptible to RPV and EFV, showing <6-fold resistance; the V106A/F227L mutant, which was >150-fold resistant to DOR, exhibited 22-fold resistance to EFV. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV L234I;V106A;V108I;F227L;L234I;V106A;V106A;V106A 34;28;40;270;17;4;11;264 39;33;45;275;22;9;16;269 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. This was followed by the emergence of Y188H/C or V179D and Y188C or L100I substitutions, respectively. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV L100I;V179D;Y188C;Y188C;Y188H 68;49;38;59;38 73;54;45;64;45 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Two resistance pathways were identified with DOR in the selection studies in subtype C virus: RT substitution V106A followed by F227I, and V106M followed by F227C. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV F227C;F227I;V106A;V106M 157;128;110;139 162;133;115;144 RT 94 96 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Two resistance pathways were observed with EFV in RT starting with L100I or V106M. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV L100I;V106M 67;76 72;81 RT 50 52 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. With RPV, RT substitution E138K was the first major resistance pathway, followed by L100I at a higher RPV concentration; as RPV concentrations further increased, the triple mutant E138K/L100I/V108I emerged. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E138K;L100I;V108I;E138K;L100I 180;186;192;26;84 185;191;197;31;89 RT 10 12 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. With the exception of Y188L, DOR also exhibited higher IQ values than RPV and EFV against the top 11 most prevalent NNRTI resistance-associated mutants. 2020 Journal of acquired immune deficiency syndromes (1999) Introduction HIV Y188L 22 27 NNRTI 116 121 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Here, we use information from the cryo-EM STC structure of the HIV-1 IN to build models of cSSC of the wild-type (WT) IN, the N155H variant, and the double mutant N155H+Q148H. 2020 Frontiers in molecular biosciences Introduction HIV N155H;N155H;Q148H 126;163;169 131;168;174 IN;IN 69;118 71;120 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Moreover, experiments with the N224H mutant of the PFV showed that the mutant only binds one ion in the active site. 2020 Frontiers in molecular biosciences Introduction HIV N224H 31 36 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. suggested that the mutation N155H causes resistance by perturbing the arrangement of Mg2+ in the active site. 2020 Frontiers in molecular biosciences Introduction HIV N155H;N155H 29;28 34;33 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The simulations were used to better understand the resistance mechanisms of N155H, as well as the reasons why N155H and Q148H are mutually exclusive. 2020 Frontiers in molecular biosciences Introduction HIV N155H;N155H;Q148H 76;110;120 81;115;125 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. There are three commonly frequent resistance pathways among the resistance mutations: N155H, Q148HRK, and Y143HC; interestingly, N155H and Q148HRK are mutually exclusive. 2020 Frontiers in molecular biosciences Introduction HIV N155H;N155H;Q148H;Q148H;Q148K;Q148K;Q148R;Q148R;Y143C;Y143H 86;129;93;139;93;139;93;139;106;106 91;134;100;146;100;146;100;146;112;112 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. This observation raises questions about the resistance mechanism behind the N155H variant since the mutated residue does not interact directly with the drug molecules. 2020 Frontiers in molecular biosciences Introduction HIV N155H 76 81 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Additionally, the M184V/I mutation occurs in the YMDD motif of reverse transcriptase (RT) causing structural changes close to the catalytic site in the enzyme which reduce RNA primer usage and decrease viral fitness through slowing viral replication. 2020 SAGE open medicine Introduction HIV M184I;M184V 18;18 25;25 RT;RT 63;86 84;88 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Although the presence of the M184V/I mutation confers high-level resistance to both 3TC and FTC, the reduction in viral replication fitness may allow for the use of less than three fully active agents while maintaining virologic suppression. 2020 SAGE open medicine Introduction HIV M184I;M184V 29;29 36;36 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. For example, many patients with the M184V/I mutation are prescribed a multiple tablet regimen containing three active agents (two NNRTs, bPI, and INSTI) based on limited prospective data indicating efficacy of this regimen. 2020 SAGE open medicine Introduction HIV M184I;M184V 36;36 43;43 INSTI 146 151 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. For most patients with the M184V/I mutation, the use of three active requires the use of more complex, multiple tablet regimens, especially in the setting of additional resistance mutations. 2020 SAGE open medicine Introduction HIV M184I;M184V 27;27 34;34 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. However, patients with major resistance, including M184V/I, are excluded from these trials. 2020 SAGE open medicine Introduction HIV M184I;M184V 51;51 58;58 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Prescribing practices vary for patients harboring the M184V/I mutation due to its effects on viral replication and NRTI susceptibilities and based on whether patients have additional resistance mutations. 2020 SAGE open medicine Introduction HIV M184I;M184V 54;54 61;61 NRTI 115 119 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Secondary objectives of the study included assessing efficacy of ART in maintaining CD4 count >200 cells/mm3 based on the number of active agents and characterizing prescribing practices for ART in patients with an M184V/I mutation. 2020 SAGE open medicine Introduction HIV M184I;M184V 215;215 222;222 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Some practitioners opt to continue 3TC or FTC in the setting of M184V/I as treatment-experienced patients have been found to experience less virologic failure and preservation of CD4 count with continuation of 3TC despite the presence of resistance. 2020 SAGE open medicine Introduction HIV M184I;M184V 64;64 71;71 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The DHHS guidelines suggest the following possible regimens for patients with the M184V/I mutation only and virologic failure: (a) continuation of same regimen, (b) bPI with two NRTIs, (c) integrase strand transfer inhibitor (INSTI) with two NRTIs, or (d) a bPI with an INSTI. 2020 SAGE open medicine Introduction HIV M184I;M184V 82;82 89;89 IN;INSTI;INSTI;NRTI;NRTI 189;226;270;178;242 198;231;275;183;247 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The M184V/I mutation also reduces susceptibilities to abacavir (ABC) and didanosine (ddI), while increasing susceptibility to zidovudine (ZDV/AZT) and tenofovir (TAF/TDF). 2020 SAGE open medicine Introduction HIV M184I;M184V 4;4 11;11 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The MOBIDIP study found that continuation of 3TC with a boosted protease inhibitor (bPI) after treatment failure in patients with the M184V mutation led to significantly less virologic failure compared with bPI monotherapy. 2020 SAGE open medicine Introduction HIV M184V 134 139 PR 64 72 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The nucleoside reverse transcriptase inhibitor (NRTI) mutation, M184V/I, is most commonly selected by two NRTIs, lamivudine (3TC) and emtricitabine (FTC) and confers high-level resistance to both agents. 2020 SAGE open medicine Introduction HIV M184I;M184V 64;64 71;71 NRTI;NRTI;NRTI 4;48;106 36;52;111 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The optimal ART for patients with the M184V/I mutation is not known. 2020 SAGE open medicine Introduction HIV M184I;M184V 38;38 45;45 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The primary objective of this study was to assess virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the ARV regimen. 2020 SAGE open medicine Introduction HIV M184I;M184V 102;102 109;109 33101270 The Signature Amino Acid Residue Serine 31 of HIV-1C Tat Potentiates an Activated Phenotype in Endothelial Cells. Several previous reports, including from our laboratory, suggested a neuroprotective function for the natural polymorphism of C31>S in HIV-1C Tat. 2020 Frontiers in immunology Introduction HIV C31S 126 131 Tat 142 145 33101270 The Signature Amino Acid Residue Serine 31 of HIV-1C Tat Potentiates an Activated Phenotype in Endothelial Cells. The results from the study suggested that the C31S substitution does not confer decreased impairment in cognitive performance. 2020 Frontiers in immunology Introduction HIV C31S 46 50 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. A major disadvantage of EFV is the low genetic barrier that certain single amino acid mutation, such as K103N, V106M, can cause a high level of drug resistance. 2020 Infection and drug resistance Introduction HIV K103N;V106M 104;111 109;116 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. For example, our group previously reported the emergence of T81A in Gag that appeared to correlate with reduced susceptibility to the modern PI lopinavir in a subtype AG-infected individual in France. 2020 mBio Introduction HIV T81A 60 64 Gag;PI 68;141 71;143 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Indeed, recent literature demonstrates that two CTL escape mutations, K94E and H116N, observed in elite controllers impair to some extent Nef's ability to internalize SERINC5. 2020 Scientific reports Introduction HIV H116N;K94E 79;70 84;74 Nef 138 141 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Here we describe a rare case of a patient with a pre-existing M184V/I mutation who failed on the ABC/3TC/DTG regimen with the emergence of resistance to all currently licensed INSTIs including the second-generation INSTIs DTG and bictegravir (BIC). 2020 Viruses Introduction HIV M184I;M184V 62;62 69;69 INSTI;INSTI 176;215 182;221 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Recently, a prospective study using data from five large HIV cohorts in four European countries assessed the efficacy of the ABC/3TC/DTG regimen in virologically suppressed, treatment-experienced patients and found no evidence for an impact of previously acquired M184V/I mutation on the incidence of virological failure. 2020 Viruses Introduction HIV M184I;M184V 264;264 271;271 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. The M184V/I mutation is one of the most common NRTI-associated mutations in HIV-1 infected patients and typically selected in patients failing on lamivudine (3TC) or emtricitabine (FTC) containing regimen. 2020 Viruses Introduction HIV M184I;M184V 4;4 11;11 NRTI 47 51 HIV infections 76 90 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. The presence of M184V/I reduces the susceptibility to these drugs by more than 100-fold and additionally causes an impaired efficacy to abacavir (ABC). 2020 Viruses Introduction HIV M184I;M184V 16;16 23;23 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. M184V/I mutations are common nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, documented in 23%-80% of people living with HIV (PLWH) experiencing virologic failure. 2021 Journal of acquired immune deficiency syndromes (1999) Introduction HIV M184I;M184V 0;0 7;7 NRTI;NRTI 29;73 61;77 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. M184V/I mutations decrease virus susceptibility to lamivudine (3TC), emtricitabine (FTC), and abacavir (ABC) but increase susceptibility to tenofovir in vitro. 2021 Journal of acquired immune deficiency syndromes (1999) Introduction HIV M184I;M184V 0;0 7;7 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. We investigated E/C/F/TAF to maintain virologic suppression in PLWH with a historical genotypic report of M184V/I when switching from TDF- or ABC-based regimens. 2021 Journal of acquired immune deficiency syndromes (1999) Introduction HIV M184I;M184V 106;106 113;113 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. However, nevirapine had no effect on PPT removal in reactions carried out with HIV-1 RT containing the drug resistance-associated substitution K103N. 2021 Viruses Introduction HIV K103N 143 148 RT 85 87 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. In a previous study, we showed that amino acid substitutions in the connection subdomain of HIV-1 RT such as N348I and T369I affect the rigidity of a hypothetical hinge connecting the DNA polymerase (residues 1-330) and the RNase H (residues 440-560) domains in the 66-kDa subunit of HIV-1 RT. 2021 Viruses Introduction HIV N348I;T369I 109;119 114;124 Pol;RT;RT 188;98;290 198;100;292 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. In addition, N348I, T369I and A376S are amino acid changes that confer resistance to nonnucleoside RT inhibitors (NNRTIs) such as nevirapine, delavirdine and efavirenz, despite being located away from the NNRTI binding site (reviewed in refs.). 2021 Viruses Introduction HIV A376S;N348I;T369I 30;13;20 35;18;25 NNRTI;NNRTI;RT 114;205;99 120;210;101 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. N348I and A376S were found with increased prevalence in nevirapine-treated patients with a higher risk of virological failure. 2021 Viruses Introduction HIV A376S;N348I 10;0 15;5 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. N348I/T369I and to a lesser extent N348I interfere with plus-strand DNA synthesis by reducing PPT removal efficiency in the presence of nevirapine and efavirenz. 2021 Viruses Introduction HIV N348I;T369I;N348I 35;6;0 40;11;5 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. PPT removal by the double-mutant N348I/T369I RT was rather inefficient since this enzyme had an impaired ability to produce short RNA products. 2021 Viruses Introduction HIV N348I;T369I 33;39 38;44 RT 45 47 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Similar effects were also reported for mutant RTs bearing single amino-acid substitutions in the connection subdomain such as T369I, T369V and T376S, and selected in patients treated with NNRTIs. 2021 Viruses Introduction HIV T369I;T369V;T376S 126;133;143 131;138;148 NNRTI;RT 188;46 194;49 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. In another study, biochemical and pull-down experiments suggested that the Q63R mutation promoted interaction with gp41CT; this mutation did not alter the organization of MA on a membrane monolayer. 2021 The Journal of biological chemistry Introduction HIV Q63R 75 79 Matrix 171 173 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. In this report, we employed NMR spectroscopy, X-ray crystallography, and analytical ultracentrifugation (AUC) techniques to characterize the structure and trimerization properties of HIV-1 MA mutants that have been shown to impair Env incorporation (L75G, A45E, and T70R) or suppress Env incorporation defects (Q63R). 2021 The Journal of biological chemistry Introduction HIV A45E;L75G;Q63R;T70R 256;250;311;266 260;254;315;270 Env;Env;Matrix 231;284;189 234;287;191 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. It was also shown that substitution of residue Gln63 with Arg suppressed Env incorporation defects of the L13E, E17K, L31E, V35E, or E99V MA mutations and of a gp41CT mutation that has the same phenotype. 2021 The Journal of biological chemistry Introduction HIV E17K;E99V;L13E;L31E;Q63R;V35E 112;133;106;118;47;124 116;137;110;122;61;128 Env;Matrix 73;138 76;140 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. It was suggested that the Q63R mutation may stabilize the trimer structure such that MA lattices, which form large hexamer holes, are favored over those that feature small hexamer holes. 2021 The Journal of biological chemistry Introduction HIV Q63R 26 30 Matrix 85 87 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Point mutations in MA (L13E, E17K, L31E, V35E, or E99V) were found to impair Env incorporation in HIV-1 particles. 2021 The Journal of biological chemistry Introduction HIV E17K;E99V;L13E;L31E;V35E 29;50;23;35;41 33;54;27;39;45 Env;Matrix 77;19 80;21 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The X-ray structure of myr(-)MA Q63R protein revealed hydrogen bonding between the side chains of adjacent Arg63 and Ser67 on neihbouring MA molecules located in the trimer interface. 2021 The Journal of biological chemistry Introduction HIV Q63R 32 36 Matrix;Matrix 29;138 31;140 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. However, a second molecular dynamics study found the opposite, with mutation K25A reducing rather than increasing the energy barrier to nucleotide import. 2021 PLoS pathogens Introduction HIV K25A 77 81 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Mutant K25A was found to increase the energy barrier and encourage dNTP movement out of the capsid. 2021 PLoS pathogens Introduction HIV K25A 7 11 Capsid 92 98 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Mutant K25I virions were non-viable and production was severely reduced, although budding virions appeared morphologically similar to wild-type, while in another study K25A/R/E/C/L Gag mutants were seen to assemble with comparable efficiency. 2021 PLoS pathogens Introduction HIV K25A;K25C;K25E;K25I;K25L;K25R 168;168;168;7;168;168 180;180;180;11;180;180 Gag 181 184 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Nevertheless, the inability of those K25A capsids that do assemble to undergo efficient reverse transcription suggests it is also required for dNTP import. 2021 PLoS pathogens Introduction HIV K25A 37 41 RT;Capsid 88;42 109;49 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Purified K25A virions are also less able to utilize dNTPs to synthesize DNA in vitro. 2021 PLoS pathogens Introduction HIV K25A 9 13 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 2016a), our recent study showed that the Vmax values of [3H]DA uptake are increased in double mutant (Y88F/H547A) and decreased in triple mutant (Y88F/K92M/H547A). 2021 Journal of neuroimmune pharmacology Introduction HIV H547A;K92M;Y88F;H547A;Y88F 156;151;146;107;102 161;155;150;112;106 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 2016a), which can be assessed by the accessibility of an inserted cysteine into position 159 residue. 2021 Journal of neuroimmune pharmacology Introduction HIV ins 159C 57 92 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Based on this theory, inserting a cysteine in position 159 alongside the H547A mutation will allow the evaluation of transporter conformational states in the H547A mutant. 2021 Journal of neuroimmune pharmacology Introduction HIV H547A;H547A 73;158 78;163 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Both Y88F and H547A attenuate the inhibitory effects of Tat on DAT function. 2021 Journal of neuroimmune pharmacology Introduction HIV H547A;Y88F 14;5 19;9 Tat 56 59 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. For example, single point mutation of hDAT at tyrosine88 (to phenylalanine, Y88F) preserves normal DA uptake, whereas DA uptake is decreased in mutation of hDAT at lysine92 (to methionine, K92M) and increased in hDAT mutation at histidine547 (to alanine, H547A). 2021 Journal of neuroimmune pharmacology Introduction HIV H547A;K92M;Y88F 255;189;76 260;193;80 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. In support of the Tat-DAT interaction model, we generated mutations on the Tat protein at lysine19 residue (to alanine, K19A) to further demonstrate these key residues at Tat interacting with DAT. 2021 Journal of neuroimmune pharmacology Introduction HIV K19A 120 124 Tat;Tat;Tat 18;75;171 21;78;174 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The accessibility of the inserted cysteine in position 159 to a compound [2-(trimethylammonium) ethyl] methanethiosulfonate (MTSET) was highly dependent upon whether the transporter was in an outward- or inward-facing conformation. 2021 Journal of neuroimmune pharmacology Introduction HIV ins 159C 25 58 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Therefore, the addition of MTSET to a DAT construct with a mutated cysteine 159 (Ile159Cys) has been shown to result in an reduction in DA uptake, allowing the use of specific DA uptake as a functional measure for I159C reactivity. 2021 Journal of neuroimmune pharmacology Introduction HIV I159C;I159C 81;214 90;219 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Thus, the current study determined the palmitoylation-mediated transport capacity in H547A using an engineered cysteine in position 159 in the hDAT-H547A mutant that renders the transporter more reactive to inactivation to MTSET or 2-bromopalmitate (2-BP), a palmitoylation inhibitor. 2021 Journal of neuroimmune pharmacology Introduction HIV H547A;H547A 85;148 90;153 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. We have recently reported that H547A enhanced DAT uptake in a protein kinase C (PKC)-dependent manner, indicating that the mutation of hDAT at His547 alters basal PKC activity. 2021 Journal of neuroimmune pharmacology Introduction HIV H547A 31 36 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. Studies have shown that even in adherent patients, those with pre-existing Y181C mutants have a triple higher risk of virological failure on an efavirenz-based cART regimen. 2021 BMC infectious diseases Introduction HIV Y181C 75 80 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. A recent work using explicit solvent molecular dynamics simulations of WT and G140S+Q148H bound with BIC and a compound without a bicyclic ring system and containing 2,4-difluorobenzyl also shows the importance of additional interactions with the IN beta4-alpha2 loop. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 78;84 83;89 IN 247 249 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. A wider distribution of the atomic displacements in the case of this truncated analog compared to BIC in WT and G140S+Q148H supports the importance of this additional anchoring interaction. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 112;118 117;123 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. BIC also dissociated more slowly than DTG from the resistant mutant G140S+Q148H IN-DNA complex, which is consistent with the greater in vitro activity of BIC than of other INSTIs against this mutant. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 68;74 73;79 INSTI;IN 172;80 178;82 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. Compounds 1 and 2 showed more resistance to G140S+Q148H than BIC, and the orientation of the bicyclic ring system (compound 2 versus BIC) had a larger impact on mutant activity than the differences in the benzyl tail (compound 1 versus BIC). 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 44;50 49;55 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. Even though very low levels of replication were observed under constant BIC pressure, BIC was able to maintain >80% of suppression of the G140S+Q148H virus after 8 days of its washout. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 138;144 143;149 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. Here, the dissociation half-life (t1/2) of BIC and other INSTIs were determined from wild-type (WT) and the clinically relevant G140S+Q148H drug-resistant mutant IN bound to IN-DNA complexes in vitro. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 128;134 133;139 INSTI;IN;IN 57;162;174 63;164;176 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. In previous washout experiments, G140S+Q148H-containing virus was able to resume replication and integration after washout of RAL or EVG. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 33;39 38;44 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. Likewise, cases of failure with emergent M184V and R263K were reported for DTG-plus-lamivudine dual therapy in the clinical trials GEMINI and ACTG5353. 2021 Antimicrobial agents and chemotherapy Introduction HIV M184V;R263K 41;51 46;56 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. The clinically relevant G140S+Q148H confers high-level resistance to RAL and EVG, 4.3-fold reduced susceptibility to DTG, and 2.1-fold reduced susceptibility to BIC. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 24;30 29;35 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. The dissociation of INSTIs from G140S+Q148H mutant IN-DNA complexes was also studied and showed that BIC had a t1/2 of 5.7 +- 0.4 h compared to 1.9 +- 0.2 h for DTG. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 32;38 37;43 INSTI;IN 20;51 26;53 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. The G140S+Q148H mutations cause varied degrees of resistance to INSTIs. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 4;10 9;15 INSTI 64 70 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. The t1/2 values of compounds 1 and 2 from G140S+Q148H IN were also different from those of BIC and DTG. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 42;48 47;53 IN 54 56 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. There was high-level resistance to RAL and EVG with G140S+Q148H mutants, resulting in an insufficient level of binding of these INSTIs to IN-DNA complexes for determination of dissociation kinetics. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 52;58 57;63 INSTI;IN 128;138 134;140 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. To probe the impact of the longer t1/2 of BIC compared with other INSTIs in cells where all cellular intasome components are present, we used HIV-1 strain NL4.3 containing WT or G140S+Q148H to infect MT-2 cells and treated with BIC or other INSTIs. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 178;184 183;189 INSTI;INSTI 66;241 72;247 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. To understand the longer t1/2 of BIC from HIV-1 IN-DNA complexes compared with that of DTG, molecular models of the INSTIs using cryo-EM structures of BIC with simian immunodeficiency virus (SIV)rcm IN (WT and G140S+Q148H mutant) or HIV-1 IN, viral DNA (vDNA) and BIC were generated. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 210;216 215;221 INSTI;IN;IN;IN 116;48;199;239 122;50;201;241 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. To understand the reduced susceptibility of INSTIs to WT and G140S+Q148H IN, t1/2 values were determined by a scintillation proximity assay as described in Hightower et al. 2021 Antimicrobial agents and chemotherapy Introduction HIV G140S;Q148H 61;67 66;72 INSTI;IN 44;73 50;75 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. A study on HIV-1 drug-resistance patterns in Nairobi identified M184V, K65R, T215Y and K70R mutations conferring resistance to NRTIs and K103N, G190A, V106A, Y184V, A98G, Y181C mutations conferring resistance to NNRTIs. 2020 The Pan African medical journal Introduction HIV A98G;G190A;K103N;K65R;K70R;M184V;T215Y;V106A;Y181C;Y184V 165;144;137;71;87;64;77;151;171;158 169;149;142;75;91;69;82;156;176;163 NNRTI;NRTI 212;127 218;132 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. At the coastal region of Kenya, L90M, M46I and D30N mutations conferring resistance to PIs were identified among out-patients injecting drug users. 2020 The Pan African medical journal Introduction HIV D30N;L90M;M46I 47;32;38 51;36;42 PI 87 90 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. As a consequence, they have a higher risk of selecting and accumulating resistance mutations, among others, M184V/I and/or K65R/E/N in the HIV reverse transcriptase. 2021 The Journal of antimicrobial chemotherapy Introduction HIV K65E;K65N;K65R;M184I;M184V 123;123;123;108;108 131;131;131;115;115 RT 143 164 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Furthermore, patients with a long history of ART exposure, such as vertically HIV-infected adolescents who have received many regimens throughout their lives, often present resistance mutations to these drugs (M184V/I and/or K65R/E/N), and it is unknown whether these simplification strategies are safe in patients with many lines of treatment and previous failures. 2021 The Journal of antimicrobial chemotherapy Introduction HIV K65E;K65N;K65R;M184I;M184V 225;225;225;210;210 233;233;233;218;218 HIV infections 78 90 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Some studies in adults have found that M184V/I, as a unique resistance mutation, did not increase the risk of virological failure in an initial follow-up period in well-controlled patients who switched to a regimen of the dual combination of dolutegravir/lamivudine. 2021 The Journal of antimicrobial chemotherapy Introduction HIV M184I;M184V 39;39 46;46 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. The objective of our study was to determine the prevalence of resistance mutations to lamivudine and emtricitabine in proviral DNA (pDNA) in youths with perinatal HIV under ART who were lamivudine and/or emtricitabine experienced, virologically suppressed for at least 1 year before sampling and carrying M184V/I and/or K65R/E/N in their historic plasma genotypes. 2021 The Journal of antimicrobial chemotherapy Introduction HIV K65E;K65N;K65R;M184I;M184V 320;320;320;305;305 328;328;328;312;312 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. Research has shown that the most reported major HIV-1 PI resistance mutations in patients failing second-line therapy in South Africa are I54V, V82A, and M46I. 2021 Biomolecules Introduction HIV I54V;M46I;V82A 138;154;144 142;158;148 PI 54 56 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. Research shows that the emergence of V32I, L33F, I47A, I50V, L76V, and 184V under drug pressure during LPV therapy may confer cross-resistance to DRV. 2021 Biomolecules Introduction HIV I47A;I50V;L33F;L76V;V32I 49;55;43;61;37 53;59;47;65;41 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The major HIV-1 PI resistance mutations that affect the efficacy of boosted LPV regimen are V32I, L33F, M46I/L, I47V/A, I50V, I54V/T/A/L/M, L76V, V82A/F/T/S, I84V. 2021 Biomolecules Introduction HIV I47A;I47V;I50V;I54A;I54L;I54M;I54T;I54V;I84V;L33F;L76V;M46I;M46L;V32I;V82A;V82F;V82S;V82T 112;112;120;126;126;126;126;126;158;98;140;104;104;92;146;146;146;146 118;118;124;138;138;138;138;138;162;102;144;110;110;96;156;156;156;156 PI 16 18 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The major PI mutations are M46I and I54V found in the flap region, L76V located in the central beta-sheet that forms one of the active site's borders, the V82A mutation, which is found in the active site; and the L90M and L33F mutations in the HIV-1 PR hydrophobic core. 2021 Biomolecules Introduction HIV I54V;L33F;L76V;L90M;M46I;V82A 36;222;67;213;27;155 40;226;71;217;31;159 PI;PR 10;250 12;252 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The minor drug resistance mutations are L10F located around the fulcrum, and the F53L:a flap mutation. 2021 Biomolecules Introduction HIV F53L;L10F 81;40 85;44 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. The assay was validated using 346 primary HIV-1 isolates from the Zurich Primary HIV-1 Infection Study (ZPHI) and two control viruses, HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V. 2021 Viruses Introduction HIV M184V 171 176 HIV infections 73 96 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. INSTI-naive highly treatment-experienced patients failing DTG cART have been found to have a virus with DRMs including G118R, D67N; H51H/Y, G118R, E138E/K, and less commonly R263R/K, V260I, R263R, N155H, G118R, and E138E. 2021 Viruses Introduction HIV D67N;E138E;E138E;E138K;G118R;G118R;G118R;H51H;H51Y;N155H;R263K;R263R;R263R;V260I 126;147;215;147;119;140;204;132;132;197;174;174;190;183 130;154;220;154;124;145;209;138;138;202;181;181;195;188 INSTI 0 5 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. Here we report the structures of two types of immature Gag assemblies bearing the T8I mutation: one from purified Gag assemblies made in bacterial cells where the Gag polyprotein was expressed; the other from purified VLPs produced in mammalian cells. 2021 Communications biology Introduction HIV T8I 82 85 Gag;Gag;Gag 55;114;163 58;117;166 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. The T8I mutation was found to promote the assembly of the Gag lattice and stabilize the alpha-helical conformation of CA-SP1. 2021 Communications biology Introduction HIV T8I 4 7 SP1;Gag;Capsid 121;58;118 124;61;120 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. We further investigated the effect of T8I mutation on Gag processing, demonstrating that PR-mediated cleavage at both SP1 boundaries was impaired. 2021 Communications biology Introduction HIV T8I 38 41 SP1;Gag;PR 118;54;89 121;57;91 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Computational modelling of RAMs against INSTIs, across different HIV-1 subtypes compared to subtype B, showed that the presence of M50I in subtypes A and C, L74I in subtypes A and CRF02_AG, G163R in CRF01_AE, and V165I in subtypes F and CRF01_AE are associated with a lower genetic barrier to resistance in non-B clades. 2021 BMC infectious diseases Introduction HIV G163R;L74I;M50I;V165I 190;157;131;213 195;161;135;218 INSTI 40 46 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Mutations that confer resistance to INSTIs (for example G140S, Q148H and N155H) have been structurally mapped in close proximity to the IN catalytic active site. 2021 BMC infectious diseases Introduction HIV G140S;N155H;Q148H 56;73;63 61;78;68 INSTI;IN 36;136 42;138 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. In both the GEMINI and TANGO studies, patients with baseline nucleoside reverse transcriptase inhibitor (NRTI) resistance include those with M184V/I and integrase strand transfer inhibitor (INSTI) resistance were excluded. 2021 AIDS research and therapy Introduction HIV M184I;M184V 141;141 148;148 NRTI;IN;INSTI;NRTI 61;153;190;105 93;162;195;109 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Prior reports have demonstrated a high prevalence of nucleoside reverse transcriptase inhibitor (NRTI) resistance and M184V/I mutation among treatment-experienced adults in LMICs, especially among those failing first-line NRTI plus NNRTI therapy and those failing second-line NRTI plus protease inhibitor (PI) therapy. 2021 AIDS research and therapy Introduction HIV M184I;M184V 118;118 125;125 NRTI;PR;NNRTI;NRTI;NRTI;NRTI;PI 53;286;232;97;222;276;306 85;294;237;101;226;280;308 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Though studies from high-income settings have demonstrated high suppression rates with the use of DTG-based regimens in the setting of pre-existing NRTI resistance including among those with an active or archived M184V/I mutation, little is currently known about the efficacy of switching to DTG-based functional mono or dual therapy in LMICs and other settings where the availability of cumulative resistance tests and complete ARV drug histories may be more limited. 2021 AIDS research and therapy Introduction HIV M184I;M184V 213;213 220;220 NRTI 148 152 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. M184V is a major NRTI mutation selected for under tenofovir and lamivudine. 2020 AAS open research Introduction HIV M184V 0 5 NRTI 17 21 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Major non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, such as K103N and V106M, are selected when HIV is exposed to nevirapine (NVP) and efavirenz, which is still used in both low and high resource settings as part of patient management. 2020 AAS open research Introduction HIV K103N;V106M 80;90 85;95 NNRTI;NNRTI 6;54 42;59 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Among them, M66I causes the greatest reduction in GS-6207 antiviral activity by up to ~84,000-fold compared to WT HIV-1 CA. 2021 Viruses Introduction HIV M66I 12 16 Capsid 120 122 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The molecular mechanism of resistance imparted by M66I and its differential effects on the binding of these antivirals is not immediately obvious from the crystal structures of the CA-compound complexes. 2021 Viruses Introduction HIV M66I 50 54 Capsid 181 183 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. This study provides mechanistic insight into the differential effects of the M66I resistance mutation against the HIV-1 capsid-targeting compounds and could help to inform the design of a new generation of antivirals with improved resistance profiles. 2021 Viruses Introduction HIV M66I 77 81 Capsid 120 126 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. To understand the detailed mechanisms of HIV-1 drug resistance through the M66I CA mutation at the atomic level, we applied MD free energy simulations in explicit solvent to study the energetics, thermodynamics, and conformational dynamics of the binding of different antivirals at the shared compound-binding site. 2021 Viruses Introduction HIV M66I 75 79 Capsid 80 82 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Using an analysis that decomposes the absolute binding free energy into contributions from two receptor conformational macrostates, we found that the free energy of the protein side chain reorganization plays a dominant role in determining the mechanism of M66I resistance to GS-6207. 2021 Viruses Introduction HIV M66I 257 261 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Among the surveillance drug-resistance mutations (SDRM), K65R is commonly associated with tenofovir (TDF) resistance and different prevalence rates of this mutation have been reported in several Brazilian cities. 2021 International journal of molecular sciences Introduction HIV K65R 57 61 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. K65R is acquired in B and several other HIV-1 subtypes by the AAA AGA substitution while in subtype C the involved substitution is AAG AGG, which has been associated with higher probability of C subtype viruses to acquire this mutation. 2021 International journal of molecular sciences Introduction HIV K65R 0 4 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. The crystal structure of M4H2K1 bound to a BG505 gp120 core at 4.3-A resolution delineated key antibody interactions with the C2/C3/V4/V5 epitope, which were confirmed in TZM-bl neutralization assays against a panel of BG505.T332N mutant viruses. 2021 mBio Introduction HIV T332N 225 230 gp120 49 54 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Three selected rabbit NAbs were tested against a panel of glycan hole variants of BG505.T332N and found to target glycan holes at 241/289 and 465. 2021 mBio Introduction HIV T332N 88 93 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. BIC/FTC/TAF has also been proven efficacious in sustaining viral suppression in individuals with documented M184V/I mutations. 2021 Open forum infectious diseases Introduction HIV M184I;M184V 108;108 115;115 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. We describe a case of treatment-emergent resistance to BIC in a person recently diagnosed with HIV who developed M184V (RT) and R263K (INI) mutations while on BIC therapy. 2021 Open forum infectious diseases Introduction HIV M184V;R263K 113;128 118;133 IN;RT 135;120 138;122 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. The main drug resistance mutations (DRMs) to TDF/FTC include K65R and M184I/V, but the global incidence was rather low in HIV ART-naive patients. 2021 BMC infectious diseases Introduction HIV K65R;M184I;M184V 61;70;70 65;77;77 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. The Stanford drug resistance database showed the incidence of K65R (1.6-3.0%) and M184I/V (30-63%) among eight common HIV-1 subtypes in NRTI-treated patients. 2021 BMC infectious diseases Introduction HIV K65R;M184I;M184V 62;82;82 66;89;89 NRTI 136 140 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Although M184V/I is well recognized as the key resistance mutation for 3TC, thymidine analog-associated mutations (TAMs) variably decrease susceptibility to all nucleoside reverse-transcriptase inhibitors (NRTIs), including 3TC. 2021 Open forum infectious diseases Introduction HIV M184I;M184V 9;9 16;16 NRTI;NRTI 161;206 193;211 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. However, long-term follow-up data about the incidence and predictors of virological failure (VF) are still lacking, with some observational reports suggesting worse virological outcomes for patients starting the DT with a shorter time of virological suppression and the presence of M184V/I at historical genotype. 2021 Open forum infectious diseases Introduction HIV M184I;M184V 282;282 289;289 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Studies with the Env endosomal recycling mutant (Y712A) virus showed the prominent accumulation of Env at the site of cell-cell contact, although with decreased Gag and increased Env translocation across VSs. 2021 Viruses Introduction HIV Y712A 49 54 Env;Env;Env;Gag 17;99;179;161 20;102;182;164 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. These mutations included M184V, K65R,D67N,K70R,K219Q,Q151M, T215F, M41L, T69N, V75M, M41L, T69N, V75M, D67G, V75M, M184I, T215N, M41LM, T215N, K219N,210W, T215Y as NRTIs; K103N/S, Y181C/Y/I/V, G190A/S, L100I,V179T, V106I/A, V108I, P225H, M230L, K238T, P225H, F227L as NNRTIs; M46I/L, D30N,M46I,V82F,L90M as PIs. 2021 The Pan African medical journal Introduction HIV D30N;D67G;D67N;F227L;G190A;G190S;K103N;K103S;K219N;K219Q;K238T;K65R;K70R;L100I;L90M;M184I;M184V;M230L;M41L;M41L;M41L;M41M;M46I;M46I;M46L;P225H;P225H;Q151M;T215F;T215N;T215N;T215Y;T69N;T69N;V106A;V106I;V108I;V179T;V75M;V75M;V75M;V82F;Y181C;Y181I;Y181V;Y181Y 284;103;37;259;193;193;171;171;143;47;245;32;42;202;299;115;25;238;67;129;85;129;276;289;276;231;252;53;60;122;136;155;73;91;215;215;224;208;79;97;109;294;180;180;180;180 288;107;41;264;200;200;178;178;148;52;250;36;46;207;303;120;30;243;71;134;89;134;282;293;282;236;257;58;65;127;141;160;77;95;222;222;229;213;83;101;113;298;191;191;191;191 NNRTI;NRTI;PI 268;164;307 274;169;310 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. Preclinical studies demonstrated MK-8507 has high antiviral potency, has a half-maximal inhibitory concentration (IC50) of approximately 50 nM, and shows only modest changes in activity to the most prevalent NNRTI-associated resistance mutations (eg, K103N, Y181C). 2022 Journal of acquired immune deficiency syndromes (1999) Introduction HIV K103N;Y181C 251;258 256;263 NNRTI 208 213 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. An evaluation of the binding activity and affinity using an enzyme linked immunosorbent assay (ELISA)-modified method and bio-layer interferometry (BLI) showed that substitution of serine (S) at position 45 with tyrosine (Y), forming AnkGAG1D4-S45Y, leads to increased affinity against the HIV-1 capsid domain. 2021 Biomolecules Introduction HIV S45S;S45Y 178;244 209;248 Capsid 296 302 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. However, in studies of dolutegravir treatment in ART-experienced, INSTI-naive individuals, there have been a small number of participants failing treatment with the uncommon INSTI resistance substitutions G118R and R263K. 2022 Antimicrobial agents and chemotherapy Introduction HIV G118R;R263K 205;215 210;220 INSTI;INSTI 66;174 71;179 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. For example, in the p51-p66 cleavage site the F440V mutation reduces replication capacity but a compensatory mutation, T477A, restores function by allowing increased flexibility and cleavage at a different site. 2022 The Journal of antimicrobial chemotherapy Introduction HIV F440V;T477A 46;119 51;124 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Also concerning is the high prevalence of the polymorphism E138A, which occurs naturally in 5% of treatment-naive HIV-1-subtype C-positive individuals and is selected by other DAPY-class NNRTIs causing 3-fold resistance to etravirine and rilpivirine. 2021 Journal of the International AIDS Society Introduction HIV E138A 59 64 NNRTI 187 193 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. In vitro studies found the L100I/K103N combination to confer the highest level of cross-resistance to DPV. 2021 Journal of the International AIDS Society Introduction HIV K103N;L100I 33;27 38;32 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The impact of circulating resistance strains or the E138A mutation on DVR protective efficacy is not known. 2021 Journal of the International AIDS Society Introduction HIV E138A 52 57 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. As a result of this, additional groups in the study were dosed with GSK'254 for 7 days, and no further emergent A364V was observed. 2022 Antimicrobial agents and chemotherapy Introduction HIV A364V 112 117 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. However, in a phase IIa study assessing GSK'795 monotherapy, participants with HIV-1 containing certain more complex Gag polymorphisms at baseline, such as V362I/V370A, displayed reduced antiviral sensitivity to GSK'795. 2022 Antimicrobial agents and chemotherapy Introduction HIV V362I;V370A 156;162 161;167 Gag 117 120 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. However, the A364A/V mutation emerged in 4 of the 6 participants receiving GSK'254 at this dose by day 11, with 1 of the 4 participants also exhibiting phenotypic resistance. 2022 Antimicrobial agents and chemotherapy Introduction HIV A364A;A364V 13;13 20;20 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In a phase IIa study, the MI bevirimat was efficacious; however, it was ineffective against viruses containing Gag polymorphisms such as V362I and other fairly common polymorphisms between amino acids 369 through 371 of the Gag protein. 2022 Antimicrobial agents and chemotherapy Introduction HIV V362I 137 142 Gag;Gag 111;224 114;227 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Over 10-day treatment with GSK'795 monotherapy ranging from 10 to 120 mg/kg of body weight, Gag polymorphisms were again detected that conferred reduced susceptibility to GSK'795, and an A364V mutation which was previously observed to confer resistance to the MI bevirimat was emergent. 2022 Antimicrobial agents and chemotherapy Introduction HIV A364V 187 192 Gag 92 95 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). Briefly, the PANDAA assay is an allelic discrimination test designed with differentially labeled TaqMan probes to discriminate wild-type DNA (K65, M184, K103, Y181 and G190) from the DRMs (substitution at a specific codon position by the mutant amino acid known as K65R, M184VI, K103NS, Y181C and G190A). 2021 The Pan African medical journal Introduction HIV G190A;K103N;K103S;K65R;M184I;M184V;Y181C 297;279;279;265;271;271;287 302;285;285;269;277;277;292 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). Several groups have developed point mutation assays (PMAs) that detect key DRMs (K65R and M184V for NRTIs; and K103NS, V106AM, Y181C, and G190A for NNRTIs) which are found in 98.8% of patients failing NNRTI-based 1st line regimens. 2021 The Pan African medical journal Introduction HIV G190A;K103N;K103S;K65R;M184V;V106A;V106M;Y181C 138;111;111;81;90;119;119;127 143;117;117;86;95;125;125;132 NNRTI;NNRTI;NRTI 148;201;100 154;206;105 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Of 700 individuals with tenofovir resistance, 578 (83%) had M184V/I mutation, 543 (78%) had major NNRTI resistance, and 457 (65%) had both. 2021 Infection and drug resistance Introduction HIV M184I;M184V 60;60 67;67 NNRTI 98 103 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Studies conducted in Ethiopia indicated that the prevalence of VF range from 5.3% to 18% among HIV/AIDS patients who were on ART for a median time of 6-24 months, while the dominant reported drug resistance mutations on RT gene were M184V, K103I, and no mutations reported on protease inhibitors associated gene. 2021 Infection and drug resistance Introduction HIV K103I;M184V 240;233 245;238 PR;RT 276;220 284;222 AIDS 99 103 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Although these mutations: IN:M50I, RH:N79S and IN:S17N, were reported NOPs mutations, we presumed that a particular ART might facilitate the emergence of the mutations and affect susceptibility to integrase inhibitor, since IN:M50I is reported as a mutation associated with resistance to dolutegravir (DTG), which enhances resistance of a mutant carrying R263K mutation to DTG, but not resistance to the drug by itself. 2021 Viruses Introduction HIV M50I;M50I;N79S;R263K;S17N 29;227;38;355;50 33;231;42;360;54 IN;IN;IN;IN 197;26;47;224 206;28;49;226 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. If a particular treatment which increases frequency of the emergence of M50I were identified, it would have a clinical advantage in designing therapies targeting the integrase. 2021 Viruses Introduction HIV M50I 72 76 IN 166 175 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Subsequently, we found that a mutant containing Met-to-Ile change at codon 50 in IN (IN:M50I) was a defect in infection/replication caused by interruption of the initiation of autoprocess step; however, due to the coexisting other NOPs, Asn-to-Ser change at codon 79 in RH (RH:N79S), or Ser to Asn mutation at codon 17 in IN (IN:S17N), the impaired replication was restored. 2021 Viruses Introduction HIV M50I;M50I;N79S;N79S;S17N;S17N 88;48;277;237;329;287 92;77;281;266;333;318 IN;IN;IN;IN 81;85;322;326 83;87;324;328 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Therefore, although the molecular mechanism of suppressing the initiation step is still unclear, we concluded that IN:M50I mutation is a lethal mutation, and RH:N79S and IN:S17N mutations are compensatory mutations for IN:M50I mutation. 2021 Viruses Introduction HIV M50I;M50I;N79S;S17N 118;222;161;173 122;226;165;177 IN;IN;IN 115;170;219 117;172;221 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We expected that variants containing the IN:M50I mutation should possess at least one of the compensatory mutations; however, 14 samples in the 529 isolates encoded only IN:M50I change. 2021 Viruses Introduction HIV M50I;M50I 44;173 48;177 IN;IN 41;170 43;172 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We report here that Val-to-Ile mutation at codon 151 of IN, IN:V151I, plays a key role in the defect in the initiation of autoprocess step. 2021 Viruses Introduction HIV V151I;V151I 63;20 68;52 IN;IN 56;60 58;62 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Primary INSTI drug resistance reported in surveillance studies are mainly substitutions that cause resistance to RAL and EVG (T66A/I, E92Q, Y143C/H/R, S147G, Q148H/K/R, and N155H pathways) and R263K, which confers low-level reduced susceptibility to EVG, DTG, and bictegravir (BIC). 2022 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E92Q;N155H;Q148H;Q148K;Q148R;R263K;S147G;T66A;T66I;Y143C;Y143H;Y143R 134;173;158;158;158;193;151;126;126;140;140;140 138;178;167;167;167;198;156;132;132;149;149;149 INSTI 8 13 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Specifically, compared with DTG, BIC has greater in vitro activity against variants with G140/Q148 mutations accompanied by 1-2 additional substitutions and variants with the E92Q/N155H combination. 2022 Journal of acquired immune deficiency syndromes (1999) Introduction HIV E92Q;N155H 175;180 179;185 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. This efficacy also extends to VS patients with certain nucleos(t)ide reverse transcriptase inhibitor (NRTI) substitutions, including M184V/I and thymidine analog substitutions. 2022 Journal of acquired immune deficiency syndromes (1999) Introduction HIV M184I;M184V 133;133 140;140 NRTI;NRTI 55;102 90;106 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. Of note, T536A mutant remained the same in all 6 clones derived from M1/VSV-G but reverted to WT T536 in all 6 clones derived from M3/VSV-G infection. 2021 Microbiology spectrum Introduction HIV T536A 9 14 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. One clone (1/18, ~5.6%) derived from M1/VSV-G infection revealed a P534T mutation. 2021 Microbiology spectrum Introduction HIV P534T 67 72 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. Our previous analysis showed that T536A variant also exists with a low frequency in 57,645 HIV-1 Env sequences from the Los Alamos National Laboratory HIV Sequence Database. 2021 Microbiology spectrum Introduction HIV T536A 34 39 Env 97 100 34935422 Reverted HIV-1 Mutants in CD4(+) T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein. We characterized three PR mutants containing S534P/T536A, S534P/T536A/T538A or S534P, named M1, M3 or M4, respectively. 2021 Microbiology spectrum Introduction HIV S534P;T536A;T538A;S534P;S534P;T536A 58;64;70;45;79;51 63;69;75;50;84;56 PR 23 25 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. All 3 participants had treatment-emergent INSTI resistance mutations of either G140R (n = 1) or Q148R (n = 2) and exhibited >5-fold reduced susceptibility to cabotegravir versus the reference virus. 2022 Antimicrobial agents and chemotherapy Introduction HIV G140R;Q148R 79;96 84;101 INSTI 42 47 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. All 3 participants with CVF were from Russia and had the integrase polymorphism L74I at baseline. 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I 80 84 IN 57 66 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Although L74I has not been observed in association with INSTI resistance (https://hivdb.stanford.edu/dr-summary/resistance-notes/INSTI/), the L74M mutation in combination with INSTI resistance-associated mutations (RAMs) T66I/K, E92V, Y143C, or N155H reduced susceptibility 14- to >200-fold to raltegravir or elvitegravir. 2022 Antimicrobial agents and chemotherapy Introduction HIV E92V;L74I;L74M;N155H;T66I;T66K;Y143C 229;9;142;245;219;219;235 233;13;146;250;227;227;240 INSTI;INSTI;INSTI 56;129;176 61;134;181 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. An updated classification algorithm reclassified the HIV-1 subtype identified in the FLAIR participants with CVF as subtype A6, which is not surprising given the prevalence of L74I in HIV-1 subtype A6 viruses from individuals in Russia. 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I 176 180 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Furthermore, L74M in combination with E92Q was found in an individual with CVF after raltegravir treatment. 2022 Antimicrobial agents and chemotherapy Introduction HIV E92Q;L74M 38;13 42;17 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Given the reported INSTI resistance associated with the L74 position and the clustering of CVF among participants with the HIV-1 subtype that was previously reported as A1 and the L74I polymorphism in FLAIR, the possibility existed of a potential association between L74I and CVF, although the majority of participants with the baseline L74I polymorphism maintained virologic suppression at Week 48 (50/54; 93%) (; https://hivdb.stanford.edu/dr-summary/resistance-notes/INSTI/). 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I;L74I;L74I 180;267;337 184;271;341 INSTI;INSTI 19;470 24;475 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In addition, each participant had treatment-emergent NNRTI resistance mutations E138K, E138E/A/K/T, or K101E (n = 1 each), with the latter 2 participants showing >2-fold reduced susceptibility to rilpivirine versus the reference virus. 2022 Antimicrobial agents and chemotherapy Introduction HIV E138A;E138E;E138K;E138K;E138T;K101E 87;87;80;87;87;103 98;98;85;98;98;108 NNRTI 53 58 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In addition, the ability of cabotegravir to suppress replication of viruses of HIV-1 subtypes B and A6 with or without L74I was evaluated. 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I 119 123 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In the LANL database, L74I is present in only 5% (8 of 149) of integrase genes in HIV-1 subtype A1 isolates but is present in 92% (70 of 76) of integrase genes in HIV-1 subtype A6 isolates (http://www.hiv.lanl.gov/). 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I 22 26 IN;IN 63;144 72;153 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In this study, the relationship between L74I and HIV-1 subtype on sensitivity to cabotegravir and rilpivirine as well as the durability of response to cabotegravir was probed. 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I 40 44 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. L74I is particularly prevalent in individuals from Russia and former Soviet Union countries, where it is present in 93% to 100% of HIV-1 subtype A isolates. 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I 0 4 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. L74M alone has minimal impact on INSTI resistance. 2022 Antimicrobial agents and chemotherapy Introduction HIV L74M 0 4 INSTI 33 38 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. L74M in combination with integrase mutations at positions 140 and 148 reduced susceptibility 6- to 12-fold to bictegravir, 10- to 12-fold to dolutegravir, and 53- to 220-fold to cabotegravir. 2022 Antimicrobial agents and chemotherapy Introduction HIV L74M 0 4 IN 25 34 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. The L74I polymorphism occurs in only 7% (404 of 5754) of integrase genes from isolates in the current Los Alamos National Laboratory (LANL) database of HIV sequences (http://www.hiv.lanl.gov/). 2022 Antimicrobial agents and chemotherapy Introduction HIV L74I 4 8 IN 57 66 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Here, we analyzed two antiviral drug-resistance-associated mutations, V260I and R263K, located within the C-terminal domain of integrase. 2021 International journal of molecular sciences Introduction HIV R263K;V260I 80;70 85;75 IN 127 136 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. The aim of this study was to evaluate the influence of the V260I and R263K mutations on the alternative splicing of HIV-1 mRNA. 2021 International journal of molecular sciences Introduction HIV R263K;V260I 69;59 74;64 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. A high prevalence of NNRTIs drug mutations was found in K103N, V106M, Y181C, and G190A. 2022 Molecules (Basel, Switzerland) Introduction HIV G190A;K103N;V106M;Y181C 81;56;63;70 86;61;68;75 NNRTI 21 27 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. informed that the mutation of K103N was detected in patients on efavirenz (EFV) more than nevirapine (NVP) treatment. 2022 Molecules (Basel, Switzerland) Introduction HIV K103N 30 35 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. K103N/ Y181C double mutations were associated with resistance to EFV and NVP NNRTI inhibitors. 2022 Molecules (Basel, Switzerland) Introduction HIV Y181C;K103N 7;0 12;5 NNRTI 77 82 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. reported NVP induced K103N, Y181C, and G190A mutations. 2022 Molecules (Basel, Switzerland) Introduction HIV G190A;K103N;Y181C 39;21;28 44;26;33 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. This research aimed to isolate potential specific anti-HIV-1 RT DNA aptamers against K103N/Y181C double mutant (KY) HIV-1 RT. 2022 Molecules (Basel, Switzerland) Introduction HIV K103N;Y181C 85;91 90;96 RT;RT 61;122 63;124 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. While Y181C was detected with NVP more than EFV. 2022 Molecules (Basel, Switzerland) Introduction HIV Y181C 6 11 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Following the Stanford algorithm (mutation list), minor resistance mutations (L10F, V11I, K20TV, L23I, L33F, K43T, F53L, Q58E, A71IL, G73STCA, T74P, N83D, and L89V) are assumed to have ancillary roles such as compensation for lower efficiency of proteolysis caused by major mutations; major resistance mutations (V32I, M46IL, I47VA, G48VM, I50VL, I54VTALM,L76V,V82ATFS, I84V,N88S, L90M) tend to confer high levels of resistance to one or multiple PI/r and develop early in patient treatment. 2022 Scientific reports Introduction HIV A71I;A71L;F53L;G48M;G48V;G73A;G73C;G73S;G73T;I47A;I47V;I50L;I50V;I54A;I54L;I54M;I54T;I54V;I84V;K20T;K20V;K43T;L10F;L23I;L33F;L76V;L89V;L90M;M46I;M46L;N83D;N88S;Q58E;T74P;V11I;V32I;V82A;V82F;V82S;V82T 127;127;115;333;333;134;134;134;134;326;326;340;340;347;347;347;347;347;370;90;90;109;78;97;103;356;159;381;319;319;149;375;121;143;84;313;361;361;361;361 132;132;119;338;338;141;141;141;141;331;331;345;345;355;355;355;355;355;374;95;95;113;82;101;107;360;163;385;324;324;153;379;125;147;88;317;368;368;368;368 PI 447 449 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. E138A was not previously included in the surveillance drug resistance mutation (SDRMs) list recommended by the World Health Organization (WHO) for the surveillance of transmitted HIV drug resistance. 2022 Clinical case reports Introduction HIV E138A 0 5 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. HIV-1 sub-subtype A6, which caused the HIV-1 epidemic in Russia, is responsible for more than 70% of HIV-infections in this region and presents with E138A polymorphic mutations in around 4%-8% of viruses, depending on the geographical region. 2022 Clinical case reports Introduction HIV E138A 149 154 HIV infections 101 115 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Our investigation of the available information on the effect of singleton polymorphic E138A mutations on RPV activity as part of first-line ART regimens provided conflicting information; so, we undertook a small study of our own to determine more localized recommendations. 2022 Clinical case reports Introduction HIV E138A 86 91 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Phenotype studies have shown that E138A mutation decreases viral susceptibility to RPV by approximately 2-fold. 2022 Clinical case reports Introduction HIV E138A 34 39 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. The aim of this study was to evaluate the virological efficacy of first-line ART regimens using RPV in HIV-1 patients with pre-existing E138A mutations in their reverse transcriptase gene. 2022 Clinical case reports Introduction HIV E138A 136 141 RT 161 182 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. The HIV Drug Resistance Stanford database defines E138A as a polymorphic mutation weakly associated with reduced susceptibility to etravirine (ETR) and RPV, whereas the French HIV Resistance database (ANRS) defines E138A viruses as fully resistant to RPV. 2022 Clinical case reports Introduction HIV E138A;E138A 50;215 55;220 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. This data means that it is generally accepted that the presence of E138A at baseline may be an indicator for subsequent ART failure. 2022 Clinical case reports Introduction HIV E138A 67 72 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Thus, in countries where HIV genotypic resistance testing (GRT) is performed before ART initiation, the presence of E138A is a counter-indicator for the use of RPV as a first-line regimen. 2022 Clinical case reports Introduction HIV E138A 116 121 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. By comparing the p-HLA structures before and after binding to the TCR, we identify the structural basis for T18A TCR recognition of HLA-B*81:01/TL9 complex and discuss the role of the unique TCR recognition in immune control of HIV. 2022 Frontiers in immunology Introduction HIV T18A 108 112 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. In this current study, we introduced the P37S and R93S (SS) single amino acid mutations to our neurotropic clone, CL757. 2022 Microbiology spectrum Introduction HIV P37S;R93S 41;50 45;54 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Interestingly, this substitution in CL757-WT, P146T, lies in a highly conserved disordered linker domain of SIV-capsid which has been shown to be critical for the proper formation of the HIV-1 capsid structure. 2022 Microbiology spectrum Introduction HIV P146T 46 51 Capsid;Capsid 112;193 118;199 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Introduction of the P37S and R93S amino acid substitutions to E543-3 and the related viral strain SIVsmmE660 (E660) allowed for better virus acquisition and more efficient replication in the presence of the restrictive TRIM5alphaTFP/TFP genotype following repetitive intrarectal challenge. 2022 Microbiology spectrum Introduction HIV P37S;R93S 20;29 24;33 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Two single amino acid mutations, P37S and R93S, found in the capsid N-terminal domain (CA-NTD), as well as amino acid substitutions 87 to 91 in the CypA binding loop (GPLPA), also in the CA-NTD, were identified as being associated with escape from TRIM5alphaTFP and TRIM5alphaCyp alleles, respectively. 2022 Microbiology spectrum Introduction HIV P37S;R93S 33;42 37;46 Capsid;Capsid;Capsid 61;87;187 67;89;189 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. This study found that the T26S mutation reduced MA-CA cutting to 25 per cent of wild-type levels and supported robust infection in cell culture, while the A28S mutation reduced cutting to about 2 per cent of wild type and resulted in non-infectious viral particles. 2021 Virus evolution Introduction HIV A28S;T26S 155;26 159;30 Matrix;Capsid 48;51 50;53 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The integration bias of the K258R mutant virus was further confirmed using quantitative PCR and in situ immunofluorescence assays. 2022 Nature communications Introduction HIV K258R 28 33 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R mutation has also been observed in databases of latent proviruses suggesting an unappreciated role in establishing viral latency. 2022 Nature communications Introduction HIV K258R 4 9 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Viruses carrying the K258R mutation in the IN protein integrate into centromeric alpha satellite repeat sequences at more than ten times the frequency observed for WT virus, as assessed by next generation sequencing (NGS) of integration sites. 2022 Nature communications Introduction HIV K258R 21 26 IN 43 45 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. Results demonstrated that 1) neutralization sensitivity was associated with evolution of the targeted domain of neutralization, not the entire envelope protein, 2) immune escape mutants gained greater resistance to bNAbs targeting different epitopes, and 3) the site (residue 465 in V5) and mutation (F277W in gp41) may be associated with immune escape. 2022 Frontiers in cellular and infection microbiology Introduction HIV F277W 301 307 Env;gp41 143;310 151;314 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Another study reported M46I as a major HIV-protease mutation in the Icelandic population. 2022 Viruses Introduction HIV M46I 23 27 PR 43 51 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Based on recently published clinical facts (a high abundance or the most prevalent mutation associated with saquinavir treatment and a greater transmission potential) on M46I-mutation-mediated saquinavir resistance in HIV patients, we considered only the M46I mutation (primary mutation) in the present study. 2022 Viruses Introduction HIV M46I;M46I 170;255 174;259 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Canducci et al., (2011) showed that a single mutation (M46I) imposed a 4.4-fold change in saquinavir resistance in mutated protease-infected CD4+ T cells in comparison to wild-type protease-infected cells. 2022 Viruses Introduction HIV M46I 55 59 PR;PR 123;181 131;189 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. It has been reported that the M46I mutation decreases the SQ interaction (1.13 times) with the protease. 2022 Viruses Introduction HIV M46I 30 34 PR 95 103 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. M46I is a non-active site mutation that occurs in the flap region of the protease. 2022 Viruses Introduction HIV M46I 0 4 PR 73 81 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Recently, a clinical study on antiretroviral treatment-naive patients in the Turkish population found the M46I mutation in high abundance. 2022 Viruses Introduction HIV M46I 106 110 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The detailed mechanism of M46I mutation in the SQ-protease interaction has not yet been established. 2022 Viruses Introduction HIV M46I 26 30 PR 50 58 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The present study was designed to provide an insight into the energetics and structural conformation changes in WT (wild-type protease), SQ-WT (saquinavir-bound wild-type protease), MI (M46I mutation-carrying protease), and SQ-MI (saquinavir-bound M46I protease) systems in a compressive mode by performing a molecular dynamics simulation approach. 2022 Viruses Introduction HIV M46I;M46I 186;248 191;252 PR;PR;PR;PR 126;171;209;253 134;179;217;261 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The study also indicated M46I as one of the most prevalent mutations related to SQ treatment in HIV patients. 2022 Viruses Introduction HIV M46I 25 29 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The study reported by Bastys et al., (2020) studied the effect of M46I and other background mutation(s) on the drug resistance potential of N88S and L76V and primary mutations in HIV-1 protease. 2022 Viruses Introduction HIV L76V;M46I;N88S 149;66;140 153;70;144 PR 185 193 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The study reported that individuals infected with a virus containing the M46I mutation in the protease accounted for increased rates of disease transmission. 2022 Viruses Introduction HIV M46I 73 77 PR 94 102 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Q148H and G140S, which confer resistance to RAL and EVG and cross-resistance to DTG, appear more frequently in subtype B than in non-B subtypes. 2022 Viruses Introduction HIV G140S;Q148H 10;0 15;5 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Similarly, R263K is mainly present in subtype B, while G118R has a pathway in selecting DTG resistance in non-B subtype viruses. 2022 Viruses Introduction HIV G118R;R263K 55;11 60;16 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Further, a Q63E mutation present in Tat subtype C was shown to contribute to higher transcriptional activation in human CD4 T cells. 2022 Frontiers in microbiology Introduction HIV Q63E 11 15 Tat 36 39 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. In a previous review done by our group, Tat protein signatures C31S, R57S, and Q63E present in Tat subtype C were reported to differentially affect mechanisms related to the development of HAND. 2022 Frontiers in microbiology Introduction HIV C31S;Q63E;R57S 63;79;69 67;83;73 Tat;Tat 40;95 43;98 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. The following HLA class I-peptide complexes were synthesized: B2705 (C67S) gag 263-272 (KRWIILGLNK), B2705 gag 263-272 (KRWIIMGLNK), A201 gag 77-85 (SLYNTVATL), A201 pol 476-484 (ILKEPVHGV), B35 nef 78-85 (VPLRPMTY), B35 gag 260-268 (PPIPVGDIY), B35 gp120 42-52 (vpvwkeatttl), B7 nef 128-137 (TPGPGVRYPL), B7 gag 148-156 (SPRTLNAWV), B8 gag 24-31 (GGKKKYKL), B8 nef 89-97(FLKEKGGL), B8 nef 13-20 (WPTVRERM), A11 pol 325-333 (AIFQSSMTK), and A11 nef 75-86 (QVPLRPMTYK). 2001 The Journal of experimental medicine Method HIV C67S 69 73 gp120;Pol;Pol;Nef;Nef;Nef;Nef;Nef;Gag;Gag;Gag;Gag;Gag;Gag 250;166;412;195;280;362;386;445;75;107;138;221;309;337 255;169;415;198;283;365;389;448;78;110;141;224;312;340 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Control reactions were carried out using an RNase H-defective mutant of RT, E478Q showing no cleavage of the RNA:DNA duplex. 2005 AIDS research and therapy Method HIV E478Q 76 81 RT 72 74 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Reactions, initiated by the addition of 25ng of each RT (corresponding to 10, 79, 16 and 28 units respectively for wild type, N255D, N265D and Dbl) were incubated at 37 C for 15 min. 2005 AIDS research and therapy Method HIV N255D;N265D 126;133 131;138 RT 53 55 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. To investigate the effect of IN mutants on viral replication, different mutants KK215,9AA, KK240.4AE, RK263,4AA or D64E were introduced into CMV-Vpr-RT-IN expressor by PCR-based method as described above and using a 5'-primer corresponding to a sequence in RT gene and including a natural NheI site (5'-GCAGCTAGCAGGGAGACTAA-3'), a 3'-primer (3'-IN-stop-PstI, 5'- CTGTTCCTGCAGCTAATCCTCATCCTG-3') and the complementary oligonucleotide primers containing desired mutations. 2005 Retrovirology Method HIV D64E 115 119 Vpr;IN;IN;IN;RT;RT 145;29;152;345;149;257 148;31;154;347;151;259 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Characterization of the substituted HIV-1 IN proteins confirmed that the 3CS/F185H/W131D/F139D derivative was the most soluble among them, and had properties comparable to the wild-type protein. 2006 Retrovirology Method HIV F139D;F185H;W131D 89;77;83 94;82;88 IN 42 44 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Construction of plasmid pET28b, encoding 6XHis - HIV-1 IN - 3CS (C56S, C65S, C280S), was previously reported. 2006 Retrovirology Method HIV C280S;C56S;C65S 77;65;71 82;69;75 IN 55 57 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The four DNA constructs specified the following substitutions: 3CS/F185H, 3CS/F185K, 3CS/F185H/W131D/F139D, and 3CS/F185K/W131D/F139D. 2006 Retrovirology Method HIV F139D;F139D;F185H;F185K;W131D;W131D;F185H;F185K 101;128;89;116;95;122;67;78 106;133;94;121;100;127;72;83 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The sIN-expressing backbone plasmid was then utilized for subsequent site-directed mutagenesis, as per the manufacturer's (Stratagene) instructions, to generate the following CTD substituted full-length sIN derivatives: F223A, R224A, Y226A, W243A, K244A, R262A, I267A, I268A, and I267A/I268A. 2006 Retrovirology Method HIV F223A;I267A;I267A;I268A;I268A;K244A;R224A;R262A;W243A;Y226A 220;262;280;269;286;248;227;255;241;234 225;267;285;274;291;253;232;260;246;239 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Using this plasmid backbone, site-directed mutagenesis (QuikChange Site-Directed Mutagenesis Kit, Stratagene) was utilized to introduce mutations encoding the amino acid substitutions F185H and/or F185K, as well as W131D and F139D, which were previously found to increase HIV-1 IN solubility. 2006 Retrovirology Method HIV F139D;F185H;F185K;W131D 225;184;197;215 230;189;202;220 IN 278 280 16956392 HIV-2 Protease resistance defined in yeast cells. pRS316Gal1/10 vectors harbouring viral Proteases from infected individuals were used as DNA template for nucleotide sequence with primers GAL (TGCATAACCACTTTAACT), hybridising with the 5' upstream region to the viral gene, and M13F (GTTTTCCCAGTCACGACG) hybridising with the 3' downstream region to the viral gene. 2006 Retrovirology Method HIV M13F 227 231 PR 39 48 16956392 HIV-2 Protease resistance defined in yeast cells. The first PCR, produced a DNA fragment coding for a truncated protease starting at its 14th amino acid and carrying the D25A mutation. 2006 Retrovirology Method HIV D25A 120 124 PR 62 70 16956392 HIV-2 Protease resistance defined in yeast cells. The genetically inactivated HIV-2ROD Protease (D25A) was constructed by 3 consecutive PCR reactions on HIV-2ROD clone14. 2006 Retrovirology Method HIV D25A 47 51 PR 37 45 16956392 HIV-2 Protease resistance defined in yeast cells. The L90M mutant was constructed by PCR using the primers Fwd and 3-90LM. 2006 Retrovirology Method HIV L90M 4 8 16956392 HIV-2 Protease resistance defined in yeast cells. The L99F HIV-2 Protease was constructed by PCR using the primers Fwd and pL99F. 2006 Retrovirology Method HIV L99F 4 8 PR 15 23 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. The cells grown up to 75% confluence were transfected with Tat expression vectors, including wild type Tat, S16A, S46A, and S16A/S46A mutant Tat plasmids using the calcium phosphate method. 2006 Retrovirology Method HIV S16A;S16A;S46A;S46A 108;124;114;129 112;128;118;133 Tat;Tat;Tat 59;103;141 62;106;144 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. The S16A and S46A mutations of the sequence of Tat were made according to the Quick-Change site-directed mutagenesis protocol of Stratagene, using the appropriate primers and templates. 2006 Retrovirology Method HIV S16A;S46A 4;13 8;17 Tat 47 50 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. These included the G431R, G431E and G431A mutations in the C4 region in combination with the gp41 wild-type GIV-SNY or mutant GIA-SKY. 2006 Retrovirology Method HIV G431A;G431E;G431R 36;26;19 41;31;24 gp41 93 97 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. For production of pHR vectors, pHR-VPR or pHR-VPR(R80A) was cotransfected with pCMVDeltaR8.2DeltaVPR, and pHCMV-VSVG by calcium phosphate-mediated transfection. 2006 PLoS pathogens Method HIV R80A 50 54 Vpr;Vpr 35;46 38;49 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. Constructs encoding N-terminal HA-tagged wild type and dominant-negative RSK2 (K100A) were provided by M. 2007 PloS one Method HIV K100A 79 84 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. Greenberg (Harvard Medical School, Boston, Massachusetts, USA), dominant-negative IKKalpha (K44M) by W. 2007 PloS one Method HIV K44M 92 96 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. Nuclear extracts from Cos7 cells transfected with Tat/FLAG, Tat F38A/FLAG, or vector alone were immunoprecipitated with alpha-RSK2 antibodies as described above. 2007 PloS one Method HIV F38A 64 68 Tat;Tat 50;60 53;63 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. O'Mahony (Gladstone Institute of Virology and Immunology, San Francisco, California, USA), dominant-negative MSK1 (R102A) and HA-tagged RSK2 and deletion mutants by M. 2007 PloS one Method HIV R102A 115 120 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. The Tat-FLAG construct served as template for site-directed mutagenesis (Stratagene) to generate the F38A mutation. 2007 PloS one Method HIV F38A 101 105 Tat 4 7 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. In addition, the model was also adjusted on use of nelfinavir at baseline and on the number of PI mutations (L10IRVF, K20RM, M36I, A71VT, G73SA, V82AFTS, L90M) found to be associated with the virological response in univariate analyses in this subset of patients. 2007 PLoS medicine Method HIV A71T;A71V;G73A;G73S;K20M;K20R;L10F;L10I;L10R;L10V;L90M;M36I;V82A;V82F;V82S;V82T 131;131;138;138;118;118;109;109;109;109;154;125;145;145;145;145 136;136;143;143;123;123;116;116;116;116;158;129;152;152;152;152 PI 95 97 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. In the original virus population of IVS-1, a mixture at amino acid R464R/K in p6gag was present, and a virus clone containing the wild-type codon at position 464 was picked. 2007 PLoS medicine Method HIV R464K;R464R 67;67 74;74 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Primary protease resistance-associated mutations were defined as any change versus wild-type at positions 23, 24, 30, 32, 46, 47, 48, 50, 54, 82, 84, 88, and 90 in the viral protease, with the following exceptions: I54V and N88D (not reported to occur without other primary mutations) and V82I (known polymorphism in PI-naive patients). 2007 PLoS medicine Method HIV I54V;N88D;V82I 215;224;289 219;228;293 PR;PR;PI 8;174;317 16;182;319 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Sequence analysis confirmed the generation of a recombinant HIV Gag clone of IVS-1 containing the K436E+I437T amino acid substitution. 2007 PLoS medicine Method HIV I437T;K436E 104;98 109;103 Gag 64 67 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Since the IVS-34 virus stock contained the K43T amino acid change in the viral protease, a virus stock from an earlier passage was used for the generation of this particular clone. 2007 PLoS medicine Method HIV K43T 43 47 PR 79 87 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. The recombinant HIV Gag clone of IVS-32 contained the I437V amino acid change. 2007 PLoS medicine Method HIV I437V 54 59 Gag 20 23 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. The recombinant HIV Gag clone of IVS-34 contained the I437T and an A15T change in p6pol. 2007 PLoS medicine Method HIV A15T;I437T 67;54 71;59 Gag 20 23 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. To generate the A128T or E170G single mutants and double mutants, site-directed mutagenesis was performed using the Kirsch and Joly method. 2007 PLoS pathogens Method HIV A128T;E170G 16;25 21;30 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. To generate the A128T, E170G, and A128T/E170G IN mutated viruses, site-directed mutagenesis was performed using the Kirsch and Joly method. 2007 PLoS pathogens Method HIV A128T;A128T;E170G;E170G 16;34;23;40 21;39;28;45 IN 46 48 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Real-time polymerase chain reaction (PCR) for sensitive detection of K65R and K70E in plasma RT-SHIV RNA. 2007 Retrovirology Method HIV K65R;K70E 69;78 73;82 Pol;RT 10;93 20;95 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Sensitive testing for the K65R and K70E mutations was performed using real-time PCR-based methodologies as described previously. 2007 Retrovirology Method HIV K65R;K70E 26;35 30;39 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The K70E test used the mutation-specific primer 70E.REV with the primer 70.FWD and probe 70.2P. 2007 Retrovirology Method HIV K70E 4 8 Rev 52 55 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The reactions for detecting the K65R mutation involved the mutation-specific primer HIV-RT 65R.FWD with the primer 65R.REV and FAM-labeled probes mixture, 1P (80%) and 2P (20%). 2007 Retrovirology Method HIV K65R 32 36 Rev;RT 119;88 122;90 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. This RT-SHIV stock had the T to C substitution at position 8 of the SIV tRNA primer binding site, which is necessary for rapid replication of RT-SHIV in vivo . 2007 Retrovirology Method HIV T8C 27 60 RT;RT 5;142 7;144 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. To evaluate the interplay of the mutations during emergence, the positive mutation-specific amplicons were directly sequenced using the primers 65-118SEQ.1R (5'-CTA GGT ATG GTA AAT GCA GTA TAC TTC CT) and RT-SEQ.2F (5'-AAG GAA GGG AAA ATT TCA AAA ATT GGG CC) for the K65R amplicon and K70E amplicon, respectively. 2007 Retrovirology Method HIV K65R;K70E 267;285 271;289 RT 205 207 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. NNRTI-selected mutations included A98G, L100I, K101E/P/N/H, K103N/S, V106A/M, V108I, V179D/E, Y181C/I/V, Y188L/C/H, G190A/S/E/Q, P225H, F227L, M230L, P236L, and K238T. 2007 PLoS computational biology Method HIV A98G;F227L;G190A;G190E;G190Q;G190S;K101E;K101H;K101N;K101P;K103N;K103S;K238T;L100I;M230L;P225H;P236L;V106A;V106M;V108I;V179D;V179E;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 34;136;116;116;116;116;47;47;47;47;60;60;161;40;143;129;150;69;69;78;85;85;94;94;94;105;105;105 38;141;127;127;127;127;58;58;58;58;67;67;166;45;148;134;155;76;76;83;92;92;103;103;103;114;114;114 NNRTI 0 5 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. NRTI-selected mutations included T39A, M41L, K43E/Q/N, E44D/A, A62V, K65R, D67N/G/E, T69D/N/S/insertion, K70R, L74V/I, V75I/M/T/A, F77L, V90I, K104N, Y115F, F116Y, V118I, Q151M, M184V/I, E203K, H208Y, L210W, T215Y/F/D/C/E/S/I/V, D218E, K219Q/E/N/R, H221Y, K223Q, and L228H/R. 2007 PLoS computational biology Method HIV A62V;D218E;D67E;D67G;D67N;E203K;E44A;E44D;F116Y;F77L;H208Y;H221Y;K104N;K219E;K219N;K219Q;K219R;K223Q;K43E;K43N;K43Q;K65R;K70R;L210W;L228H;L228R;L74I;L74V;M184I;M184V;M41L;Q151M;T215C;T215D;T215E;T215F;T215I;T215S;T215V;T215Y;T39A;T69D;T69N;T69S;V118I;V75A;V75I;V75M;V75T;V90I;Y115F 63;229;75;75;75;187;55;55;157;131;194;249;143;236;236;236;236;256;45;45;45;69;105;201;267;267;111;111;178;178;39;171;208;208;208;208;208;208;208;208;33;85;85;85;164;119;119;119;119;137;150 67;234;83;83;79;192;61;61;162;135;199;254;148;247;247;247;247;261;53;53;53;73;109;206;274;274;117;117;185;185;43;176;227;227;227;227;227;227;227;227;37;93;93;93;169;129;129;129;129;141;155 NRTI 0 4 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. PI-selected mutations included L10I/V/F/R, V11I, K20R/M/I/T, L23I, L24I, D30N, V32I, L33F/I, E34Q, E35G, M36I/V, K43T, M46I/L/V, G48V/M, I50V/L, F53L, I54V/M/L/T/A/S, K55R, Q58E, L63P, I66F, C67F, A71V/T/I, V72L, G73S/T/C/A, T74A/P/S, L76V, V77I, V82A/T/F/S/L/M, I84V/A/C, I85V, N88D/S/T/G, L89V, L90M, T91S, Q92R/K, I93L, and C95F. 2007 PLoS computational biology Method HIV A71I;A71T;A71V;C67F;C95F;D30N;E34Q;E35G;F53L;G48M;G48V;G73A;G73C;G73S;G73T;I50L;I50V;I54A;I54L;I54M;I54S;I54T;I54V;I66F;I84A;I84C;I84V;I85V;I93L;K20I;K20M;K20R;K20T;K43T;K55R;L10F;L10I;L10R;L10V;L23I;L24I;L33F;L33I;L63P;L76V;L89V;L90M;M36I;M36V;M46I;M46L;M46V;N88D;N88G;N88S;N88T;Q58E;Q92K;Q92R;T74A;T74P;T74S;T91S;V11I;V32I;V72L;V77I;V82A;V82F;V82L;V82M;V82S;V82T 197;197;197;191;327;73;93;99;145;129;129;213;213;213;213;137;137;151;151;151;151;151;151;185;263;263;263;273;317;49;49;49;49;113;167;31;31;31;31;61;67;85;85;179;235;291;297;105;105;119;119;119;279;279;279;279;173;309;309;225;225;225;303;43;79;207;241;247;247;247;247;247;247 205;205;205;195;331;77;97;103;149;135;135;223;223;223;223;143;143;165;165;165;165;165;165;189;271;271;271;277;321;59;59;59;59;117;171;41;41;41;41;65;71;91;91;183;239;295;301;111;111;127;127;127;289;289;289;289;177;315;315;233;233;233;307;47;83;211;245;261;261;261;261;261;261 PI 0 2 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Q151M-associated mutations included A62V, V75I, F77L, F116Y, and Q151M. 2007 PLoS computational biology Method HIV A62V;F116Y;F77L;Q151M;V75I;Q151M 36;54;48;65;42;0 40;59;52;70;46;5 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Recently described accessory NRTI mutations included T39A, K43E/Q/N, E44D/A, V118I, E203K, H208, D218E, H221Y, K223Q, and L228H/R. 2007 PLoS computational biology Method HIV D218E;E203K;E44A;E44D;H221Y;K223Q;K43E;K43N;K43Q;L228H;L228R;T39A;V118I 97;84;69;69;104;111;59;59;59;122;122;53;77 102;89;75;75;109;116;67;67;67;129;129;57;82 NRTI 29 33 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. These mutations included the Type I TAMs M41L, L210W, and T215Y, and the Type II TAMs D67N, K70R, T215F, and K219Q/E. 2007 PLoS computational biology Method HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 86;109;109;92;47;41;98;58 90;116;116;96;52;45;103;63 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. pCDNA3.1-Ubiquitin K48R was provided by M. 2007 Virology journal Method HIV K48R 19 23 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. pHR-VPR-IRES-GFP (herein referred to as pHR-VPR), pHR-VPR(R80A)-IRES-GFP and pHR-GFP, were produced and titered as previously described. 2007 Virology journal Method HIV R80A 58 62 Vpr;Vpr;Vpr 4;44;54 7;47;57 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. The Q65R mutation in Vpr was made in pHR-VPR using Quikchange II XL (Stratagene). 2007 Virology journal Method HIV Q65R 4 8 Vpr;Vpr 21;41 24;44 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. The three HIV-1 CAp24 mutants, D51N, D51E, and D51Q, in the pET11a-CA vector were then engineered by site-directed mutagenesis using the Stratagene's QuickChange Site Directed Mutagenesis Kit (Stratagene) as recommended by the manufacturer. 2007 Retrovirology Method HIV D51E;D51N;D51Q 37;31;47 41;35;51 Capsid;Capsid 16;67 18;69 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Afterward, cells were harvested, stained with PE-labeled B2705 KK10 or L6M pentamers and CD8 APC antibodies, and subjected to flow cytometric analysis using a FACSCalibur instrument. 2007 The Journal of experimental medicine Method HIV L6M 71 74 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. MDDCs generated as described above were matured for 16-20 h in the presence of HLA-B27 KK10 WT or L6M pentamers and then mixed with allogenic CFSE-labeled PBMCs. 2007 The Journal of experimental medicine Method HIV L6M 98 101 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. PBMCs (106/ml) were stained with 0.25 muM CFSE and incubated for 6 d in the presence of the KK10 WT or L6M peptide. 2007 The Journal of experimental medicine Method HIV L6M 103 106 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Recombinant HLA-B27 KK10 WT or L6M tetramers (obtained from the National Institutes of Health [NIH]/National Institute of Allergy and Infectious Diseases tetramer core facility) at a concentration of 2mg/ml in 10 mM sodium acetate, pH 4.6, were individually immobilized (600 resonance units) to a CM5 sensor chip (BIAcore) using standard amine coupling methods. 2007 The Journal of experimental medicine Method HIV L6M 31 34 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. To characterize the binding affinity between HLA-B27 KK10 WT or L6M complexes and ILT4 in a cell-free system, SPR experiments were performed using a BIAcore 3000 SPR instrument (BIAcore) in 10 mM Hepes buffer containing 150 mM sodium chloride, 3.4 mM EDTA, and 0.005% (vol/vol) surfactant P-20 at 25 C. 2007 The Journal of experimental medicine Method HIV L6M 64 67 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Most of the yeast and mammalian expression plasmids used in this study have been described previously, except plasmids for expression of the Vpr mutants with L23F and K27M substitutions; the Vpr mutant with the R80A substitution was kindly provided by E. 2007 Retrovirology Method HIV K27M;L23F;R80A 167;158;211 171;162;215 Vpr;Vpr 141;191 144;194 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Mutations (L23F, K27M) were thus performed using pUC19-VprYU-2 as a matrix by site-directed mutagenesis with specific primers: L23F-F ACACTAGAG CTTTTTGAGGAGCTTAAG, L23F-R CTTAAGCTCCTCAAAAAGCTCTAGTGT, K27M-F CTTTTAGAGGAGCTTATGAGAGAAGCTGTTAG, K27M-R CTAACAGCTTCTCTCATAA GCTCCTCTAAAAG. 2007 Retrovirology Method HIV K27M;K27M;K27M;L23F;L23F;L23F 17;200;241;11;127;164 21;204;245;15;131;168 Matrix 68 74 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Since one variant contained several point mutations (L23F, L67Q, and R73G; see on. 2007 Retrovirology Method HIV L23F;L67Q;R73G 53;59;69 57;63;73 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. The L23F and K27M mutants were constructed by PCR-mediated site-directed mutagenesis using specific primers containing the desired mutations. 2007 Retrovirology Method HIV K27M;L23F 13;4 17;8 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Bevirimat-resistant NL4-3 SP1/A1V (also designated as A364V based on the full Gag sequence) was supplied by Panacos Pharmaceuticals. 2007 PloS one Method HIV A1V;A364V 30;54 33;59 SP1;Gag 26;78 29;81 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Stocks of NL4-3 and SP1/A1V were prepared by transfection of 293T cells and collection of supernatants on days 2 or 3. 2007 PloS one Method HIV A1V 24 27 SP1 20 23 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The AZT-resistant (M41L, T215Y) R5X4 clinical HIV-1 isolate JD was kindly provided by Mike McCune and prepared by cocultivation of patient peripheral blood mononuclear cells (PBMCs) and expansion in phytohemagglutinin (PHA)-activated PBMCs. 2007 PloS one Method HIV M41L;T215Y 19;25 23;30 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. To determine the effect of bevirimat on CA maturation of protease inhibitor-resistant HIV-1, Western blot analysis was performed on HIV-1 NL4-3 and NL4-3 PRI54V+V82A virions collected from transfected 293T cells treated with 20 microM bevirimat as described above using a p24 specific monoclonal antibody (AIDS Reagent Program). 2007 PloS one Method HIV V82A 161 165 PR;p24;Capsid;PR 57;272;40;154 65;275;42;156 AIDS 306 310 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. We introduced the I54V and V82A protease inhibitor resistance substitutions into the protease gene of HIV-1 NL4-3 by site-directed mutagenesis to produce NL4-3 PRI54V+V82A. 2007 PloS one Method HIV I54V;I54V;V82A;V82A 18;162;167;27 22;166;171;31 PR;PR;PR 32;85;160 40;93;162 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Analysis of Drug Treatment Associated with Emergence of N348I. 2007 PLoS medicine Method HIV N348I 56 61 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Association of N348I and TAMs with Changes in Viral Load. 2007 PLoS medicine Method HIV N348I 15 20 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Association of N348I with Key Drug Resistance Mutations. 2007 PLoS medicine Method HIV N348I 15 20 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. For the analysis of the association of N348I and TAMs with changes in viral load, the DeltapVL values were assessed for normality as determined visually by normal probability plots and by the one-sample Kolmogorov-Smirnov goodness-of-fit test. 2007 PLoS medicine Method HIV N348I 39 44 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In the descriptive analysis used to determine which antiretroviral drug treatment was associated with the emergence of N348I, categorical variables were compared using the Chi-square or Fisher Exact test, and continuous variables were compared using the Wilcoxon rank-sum test. 2007 PLoS medicine Method HIV N348I 119 124 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Neither N348I nor other key drug resistance mutations, as defined by the IAS-USA guidelines, were detected in the viral genomes at the start of antiretroviral therapy. 2007 PLoS medicine Method HIV N348I 8 13 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Pattern of Appearance of N348I Early in Drug Therapy. 2007 PLoS medicine Method HIV N348I 25 30 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Statistical analyses of the prevalence of mutations from codons 240 to 400 in drug-naive compared to drug-treated individuals and the association of N348I with key drug resistance mutations were performed using the Chi-square test. 2007 PLoS medicine Method HIV N348I 149 154 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The analysis excluded sequencing data that were not performed up to codon 400 and did not account for other IAS-USA defined RT or PI drug resistance mutations that may have been selected with N348I or TAMs. 2007 PLoS medicine Method HIV N348I 192 197 PI;RT 130;124 132;126 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The analysis was performed for N348I and for each of the TAMs: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E. 2007 PLoS medicine Method HIV D67N;K219E;K219Q;K70R;L210W;M41L;N348I;T215F;T215Y 69;101;101;75;81;63;31;88;88 73;108;108;79;86;67;36;95;95 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The last on-therapy sample from a total of 3,569 patients was analysed for the association of N348I with key drug resistance mutations (n = 161) compared to the prevalence of key mutations in the absence of N348I (n = 3,408). 2007 PLoS medicine Method HIV N348I;N348I 94;207 99;212 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The M41L, L210W, T215Y, and N348I mutations were introduced into WT HIV-1LAI RT by site-directed mutagenesis using the QuikChange Mutagenesis kit. 2007 PLoS medicine Method HIV L210W;M41L;N348I;T215Y 10;4;28;17 15;8;33;22 RT 77 79 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The time in days after initiation of antiretroviral therapy of the first appearance of N348I and key drug resistance mutations was determined. 2007 PLoS medicine Method HIV N348I 87 92 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. To determine which antiretroviral drug treatment was associated with the emergence of N348I, an explanatory logistic regression model was developed for identifying which patient characteristics were most influential in the emergence of N348I during antiretroviral therapy. 2007 PLoS medicine Method HIV N348I;N348I 86;236 91;241 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Where N348I appeared at a time point immediately following its first appearance, any new key mutations, which had not appeared previously, were also recorded. 2007 PLoS medicine Method HIV N348I 6 11 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. mt3: (D24A) K211I, S345T, E350K. 2008 Nucleic acids research Method HIV K211I;D24A;E350K;S345T 12;6;26;19 17;10;31;24 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. mt4: (D24A) K211I, I224T, S345T, E350K. 2008 Nucleic acids research Method HIV K211I;D24A;E350K;I224T;S345T 12;6;33;19;26 17;10;38;24;31 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. The activities of the mutants were compared to wild-type PR-RT either without or with the PR D24A mutation (WT and WT*, respectively). 2008 Nucleic acids research Method HIV D24A 93 97 PR;PR;RT 57;90;60 59;92;62 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. Thus the AZT-resistant mutants also contain the D24A mutation in the PR. 2008 Nucleic acids research Method HIV D24A 48 52 PR 69 71 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. To avoid degradation of the PR-RT by autocatalytic activity of the PR, a mutant enzyme was constructed harboring an active site mutation in the PR region (D24A), which leads to an inactive PR. 2008 Nucleic acids research Method HIV D24A 155 159 PR;PR;PR;PR;RT 28;67;144;189;31 30;69;146;191;33 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. The annealed oligonucleotides consisted of 5' GAT CTG TAT CCT TTA GCT TCC CTC AGA TCA CTC TTT GGC AGC GA 3', 5' CCC CTC GTC ACA ATA AAG ATA GGG GGG CAA TTA AAG GAA GCT CTA TTA GAT T 3', 5' CCG GAA TCT AAT AGA GCT TCC TTT AAT TGC CCC CCT ATC TTT ATT GTG ACG A 3', 5' GGG GTC GCT GCC AAA GAG TGA TCT GAG GGA AGC TAA AGG ATA CA 3' and were used to fuse Vpr in frame to PR at the Bgl II site while maintaining the PR cleavage site and inserting a T26S mutation (ACA changed to TCC) thereby creating a BspEI site. 2007 Retrovirology Method HIV T26S 443 447 Vpr;Tat;Gag;Gag;Capsid;PR;PR 350;54;286;298;322;366;410 353;57;289;301;324;368;412 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. 611 nucleotides (HXB2 position 1903 to 2513) were included in the phylogenetic analysis to accommodate nucleotide sequence unavailable from the shorter L90M specific amplicons and low quality sequence data immediately adjacent to the sequencing primer. 2008 Retrovirology Method HIV L90M 152 156 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Amplification of L90M variants from E. 2008 Retrovirology Method HIV L90M 17 21 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. coli colonies was performed by touching a sterile toothpick to each colony and the toothpick then rubbed on the inside of a L90M specific PCR reaction mixture followed by only eight cycle of L90M specific PCR amplification (using AK90m and AKG3). 2008 Retrovirology Method HIV L90M;L90M 124;191 128;195 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Input DNA into the L90M specific PCR consisted of PCR DNA generated from either plasmids or from cDNA from clinical samples using the nested PCR generic gag-pro primers. 2008 Retrovirology Method HIV L90M 19 23 Gag 153 156 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. L90M specific amplification products generated with AK90m and AKG3 were purified using Quiagen PCR product purification kit and sequenced using primer AKG3. 2008 Retrovirology Method HIV L90M 0 4 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. pAK90M has the L90M mutation (methionine codon 90 = ATG) while pAKL90 is wild type L90 (leucine codon 90 = TTG). 2008 Retrovirology Method HIV L90M 15 19 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. pAKL90 and pAK90M also differ at 15 nucleotides positions within the fragment amplified by the L90M specific PCR. 2008 Retrovirology Method HIV L90M 95 99 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Second round PCR DNA was purified using Quiagen PCR product purification columns, diluted 1:100 in water and 10 mul of dilution was used as input for the L90M selective PCR. 2008 Retrovirology Method HIV L90M 154 158 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Selective amplification of minority variant carrying L90M protease mutation. 2008 Retrovirology Method HIV L90M 53 57 PR 58 66 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The L90M specific amplicons were 689 nucleotides. 2008 Retrovirology Method HIV L90M 4 8 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The L90M specific primer was AK90m (AAAGTGCAACCAATCTGACCAT HXB2 positions 2520-2542) used together with AKG3 (ACCCGGCCATAAAGCAAG HXB2 positions 1853-1871) in a final PCR reaction volume of 50 mul containing 10 mM Tris-HCl pH 9.0, 50 mM KCl, 2.5 mM MgCl2, 0.1% triton-X100, 2.5 mM of each dNTP, 15 pmol of each primer and 3.5 U Hot start Taq polymerase. 2008 Retrovirology Method HIV L90M 4 8 Pol 341 351 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Analysis of E40F and K43E prevalence and associations. 2008 Retrovirology Method HIV E40F;K43E 12;21 16;25 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Genotyping revealed that the increase in RNA load was associated with the appearance of M41L, L210W and T215Y. 2008 Retrovirology Method HIV L210W;M41L;T215Y 94;88;104 99;92;109 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Later on, a further increase in HIV-1 RNA level was observed and the viral genotype showed the appearance of the E40F and K43E changes. 2008 Retrovirology Method HIV E40F;K43E 113;122 117;126 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. This patient was treated with Lamivudine (3TC) monotherapy and selected the M184V change. 2008 Retrovirology Method HIV M184V 76 81 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To change the E40F substitution to wild type in the patient A-derived virus clone (Pat A-WT40) primer 40E-RT (5'-GAA ATT TGT ACA GAG TTG GAA GAG G-3', nucleotides 2655-2679) was used. 2008 Retrovirology Method HIV E40F 14 18 RT 106 108 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To delete the K43E substitution from the patient A-derived virus clone (Pat A-WT43), the corresponding plasmid was amplified with as third primer 43K-RT (5'-ACA TTT TTG GAA AAG GAA GGA AA-3', nucleotides 2664-2686). 2008 Retrovirology Method HIV K43E 14 18 RT 150 152 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To determine the influence of the E40F and/or K43E amino acid substitutions, these changes were introduced in a wild type reference strain (HIV-1 HXB2) and a virus clone harbouring the M41L and T215Y amino acid changes. 2008 Retrovirology Method HIV E40F;K43E;M41L;T215Y 34;46;185;194 38;50;189;199 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To introduce the E40F change in the M41L+215Y reference plasmid primers 40F-RT1 (5' GAA ATT TGT ACA TAG CTG GAA AAG G-3', nucleotides 2655-2679), 40F-RT2 5' GAA ATT TGT ACA TTG CTG GAA AAG G-3', nucleotides 2655-2679) and 40F-RT3new 5' GAA ATT TGT ACA TTT CTG GAA AAG GA-3', nucleotides 2655-2680) were used. 2008 Retrovirology Method HIV E40F;M41L 17;36 21;40 RT;RT;RT 76;150;226 78;152;228 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To introduce the K43E change in respectively the wild type plasmid, the plasmid containing M41L+T215Y or the M41L+T215Y+E40F plasmid, the primers HXB2-43E (5' ACA GAG ATG GAA GAG GAA GGG AAA A-3', nucleotides 2664-2688), 43E-RT (5' ACA GAG CTG GAA GAG GAA GGG AAA A-3', nucleotides 2664-2688) and 43E-RTA (5' ACA TTT CTG GAA GAG GAA GGG AA-3', nucleotides 2664-2686) were used. 2008 Retrovirology Method HIV E40F;K43E;M41L;M41L;T215Y;T215Y 120;17;91;109;96;114 124;21;95;113;101;119 RT 225 227 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). Figure 1 shows the plasmid construct used to generate a recombinant virus (referred to as MVA-BAC-parent) containing the entire sequence of the BAC vector pBELO-BAC11 at the Deletion III locus of MVA (between the remnants of A51R and A56R) together with a GFP reporter gene driven by the p4B late promoter from Fowlpox virus. 2008 PloS one Method HIV A51R;A56R;A51R;A56R 226;235;225;234 230;239;229;238 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. WT RT refers to the wild type enzyme, and "TAMs" refers to mutants that contain the following amino acid substitutions: M41L, D67N, L210W, and T215Y. 2008 The Journal of biological chemistry Method HIV D67N;L210W;M41L;T215Y 128;134;122;145 132;139;126;150 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. As such, it will be referred to as the "21-bp hybrid duplex." The hybrid was incubated with 100 nm WT RT and TAMs/A360V/N348I, respectively, in a buffer containing 50 mm NaCl and 50 mm Tris-HCl, pH 7.8. 2008 The Journal of biological chemistry Method HIV A360V;N348I 114;120 119;125 RT 102 104 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. TAMs/A360V contains in addition to these four changes the A360V connection domain mutation. 2008 The Journal of biological chemistry Method HIV A360V;A360V 5;58 10;63 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. TAMs/E478Q and TAMs/A360V/N348I/E478Q are equivalent, RNase H-negative mutants (supplemental. 2008 The Journal of biological chemistry Method HIV A360V;E478Q;N348I;E478Q 20;32;26;5 25;37;31;10 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The same nomenclature is applied to the other mutants used in this study: TAMs/N348I and TAMs/A360V/N348I. 2008 The Journal of biological chemistry Method HIV A360V;N348I;N348I 94;100;79 99;105;84 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. The assay cutoff for mutation detection was 0.5% for K103N and G190A, and 1.0% for Y181C. 2008 The Journal of infectious diseases Method HIV G190A;K103N;Y181C 63;53;83 68;58;88 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The optimized HIV-1 PR clone with mutations Q7K, L33I, and L63I to diminish the autoproteolysis of the PR, as well as mutations C67A and C95A to prevent cysteine-thiol oxidation was used as the initial template for adding drug resistant mutations. 2008 Journal of molecular biology Method HIV C67A;C95A;L33I;L63I;Q7K 128;137;49;59;44 132;141;53;63;47 PR;PR 20;103 22;105 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. To quantify the proportion of mutant sequences contained within each specimen, 5 microl of the RT-PCR products were added to PCR reactions that permitted nonselective amplification of HR-1-coding sequences or selective amplification of sequences containing the V38A mutation. 2008 Journal of acquired immune deficiency syndromes (1999) Method HIV V38A 261 265 RT 95 97 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. The 303 samples in the mutant group were tested for minority mutations not detected by conventional genotyping, which included 222 for L90M, 101 for M41L, 251 for K70R, 202 for K103N, 200 for Y181C, 260 for M184V, and 209 for 215Y/F mutations. 2008 PLoS medicine Method HIV K103N;K70R;L90M;M184V;M41L;Y181C 177;163;135;207;149;192 182;167;139;212;153;197 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. We tested these samples for three treatment-relevant reverse transcriptase (RT) mutations, K103N, Y181C, and M184V. 2008 PLoS medicine Method HIV K103N;M184V;Y181C 91;109;98 96;114;103 RT;RT 53;76 74;78 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. Wild-type virus samples were tested for eight mutations: L90M in PR; and M41L, K70R, K103N, Y181C, M184V, and T215Y/F in RT. 2008 PLoS medicine Method HIV K103N;K70R;L90M;M184V;M41L;T215F;T215Y;Y181C 85;79;57;99;73;110;110;92 90;83;61;104;77;117;117;97 PR;RT 65;121 67;123 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. PCR products generated in the ViroSeq system were also analyzed using the LigAmp assay to detect and quantify HIV variants with NVP resistance mutations (K103N=AAC, 0.5% assay cutoff; Y181C=TGT, 1% assay cutoff; G190A=GCA, 0.5% assay cutoff). 2008 The Journal of infectious diseases Method HIV G190A;K103N;Y181C 212;154;184 217;160;189 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. The LigAmp assay was performed as previously described, with the following exception: for Y181C detection, two upstream oligonucleotides were used because of sequence diversity at the oligonucleotide binding site. 2008 The Journal of infectious diseases Method HIV Y181C 90 95 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Molecular clones carrying the Asn-269 (T271I), Asn-342 (N342Y) or the Asn-269/Asn-342 double mutant (Delta2N) were transfected into 293T cells using Superfect (QIAGen) and recovered by co-culture with MYA-1 cells at 72 hrs post-transfection. 2008 Retrovirology Method HIV N342Y;T271I 56;39 61;44 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The FL4 strain of FIV lacks sites for N-linked glycosylation at Asn-269 due to a threonine to isoleucine switch at 271 (T271I), and Asn-342 due to an asparagine to tyrosine substitution at 342 (N342Y). 2008 Retrovirology Method HIV N342Y;N342Y;T271I;T271I 194;150;120;81 199;192;125;118 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. The impacts of the L23F mutation in the first alpha-helix, the DeltaQ44 deletion in the second helix and the I60A and L67A mutations in the third alpha-helix [54-77] on the 3D structure of Vpr have been investigated by in silico procedure. 2008 Retrovirology Method HIV I60A;L23F;L67A 109;19;118 113;23;122 Vpr 189 192 18809675 Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. A T-20-sensitive NL4-3 D36G (NL4-3G) was altered by site-directed mutagenesis to match the consensus sequence at amino acid position 36 (aspartic acid replaced by glycine) of gp41. 2008 The Journal of biological chemistry Method HIV D36G 24 28 gp41 178 182 18809675 Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. pNL4-3 from the AIDS Reagent Program contains an unexpected variant DIV (G36D) mutation in gp41, which confers 8-fold resistance to T-20 in vitro. 2008 The Journal of biological chemistry Method HIV G36D 74 78 gp41 92 96 AIDS 16 20 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. In addition, we have used QuikChange site-directed mutagenesis to generate the Env mutant DS17(N283T), in which the N283 residue present in the DS17 clone was mutated to T. 2008 Retrovirology Method HIV N283T 95 100 Env 79 82 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. To evaluate the role of N283 in various Env backgrounds, the Env mutants pSV-BR(N283T) and pSV-SPL(T283N) where the N283 present in the brain Env was mutated to T and the T283 present in the spleen Env was mutated to N, respectively, were created using QuikChange site-directed mutagenesis (Stratagene, La Jolla, CA) following manufacturer's instructions. 2008 Retrovirology Method HIV N283T;T283N 80;99 85;104 Env;Env;Env;Env;Capsid 40;61;142;198;313 43;64;145;201;315 18925934 Peptide P5 (residues 628-683), comprising the entire membrane proximal region of HIV-1 gp41 and its calcium-binding site, is a potent inhibitor of HIV-1 infection. The envelope proteins of the two other viruses, T20-1 and T20-2, as well as the virus populations from which they were derived, expressed the V38A resistance mutation. 2008 Retrovirology Method HIV V38A 142 146 Env 4 12 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In the quantitative analysis, L63P and M36I were not counted as minor mutations for subtypes B and F1, respectively, as they represent frequent polymorphisms found in those respective subtypes. 2009 Infection, genetics and evolution Method HIV L63P;M36I 30;39 34;43 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Mutations D30N (NFV), V32I (LPV), M46I/L (IDV/RTV), I47V/A (LPV/RTV), G48V (SQV), I50L/V (APV), V82A/F/T/S (LPV/IDV/RTV), I84V (APV/IDV/RTV) and L90M (SQV/NFV) were considered as major resistance mutations and were analyzed separately for each PI as well as quantitatively all together. 2009 Infection, genetics and evolution Method HIV D30N;G48V;I47A;I47V;I50L;I50V;I84V;L90M;M46I;M46L;V32I;V82A;V82F;V82S;V82T 10;70;52;52;82;82;122;145;34;34;22;96;96;96;96 14;74;58;58;88;88;126;149;40;40;26;106;106;106;106 PI 244 246 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Mutations L10F/I/R/V, K20M/R, L24I, L33F, M36I, F53L, I54V/L/A/M/T/S, L63P, A71V/T, G73C/S/T/A, V77I and N88D/S were considered as minor resistance mutations and were also analyzed separately and together as a group. 2009 Infection, genetics and evolution Method HIV A71T;A71V;F53L;G73A;G73C;G73S;G73T;I54A;I54L;I54M;I54S;I54T;I54V;K20M;K20R;L10F;L10I;L10R;L10V;L24I;L33F;L63P;M36I;N88D;N88S;V77I 76;76;48;84;84;84;84;54;54;54;54;54;54;22;22;10;10;10;10;30;36;70;42;105;105;96 82;82;52;94;94;94;94;68;68;68;68;68;68;28;28;20;20;20;20;34;40;74;46;111;111;100 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. D67N/K70R/T215F/K219Q (TAM67) and TAM67/K65R HIV-1 RT were generated by site-directed mutagenesis of WT HIV-1LAI RT. 2008 AIDS (London, England) Method HIV K219Q;K70R;T215F;K65R;D67N 16;5;10;40;0 21;9;15;44;4 RT;RT 51;113 53;115 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Reactions were initiated by the addition of 50 nM wild-type (WT) or mutant (TAM67 or TAM67/K65R) HIV-1 RT. 2008 AIDS (London, England) Method HIV K65R 91 95 RT 103 105 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. The mutations we examined, by drug category were: lamivudine (184I/V); any other nucleoside reverse transcriptase inhibitors (41L, 62V, 65R, 67N, 69D or insertion, 70R, 74V, 75I, 151M, 210W, 215F/Y or 219E/Q); any non-nucleoside reverse transcriptase inhibitors (100I, 103N, 106A/M, 108I, 181C/I, 188C/H/L, 190A/S, P225H, M230L or 236L); and any protease-inhibitors (30N, 33F, 46I/L, 48V, 50L/V, 54V/L/M, 82A/F/S/T, 84V, or 90M). 2008 AIDS (London, England) Method HIV M230L;P225H 322;315 327;320 NNRTI;NRTI;PR 214;81;346 250;113;354 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. Four G190A isolates from a large transmission cluster (n=27), (GenBank accession numbers EU375798-EU375801), were assessed for baseline susceptibility to nevirapine (NVP), efavirenz (EFV), etravirine (ETV) and TMC-120. 2008 AIDS (London, England) Method HIV G190A 5 10 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. HP16 cells harboring either p424-Gal1-IN wild type or p424-Gal1-IN encoding the V165P, A179P or KR186,7AA mutants were grown at 30 C in IN-non-inducible (Trp-, 2% raf+) media to a cell density of 0.25 A600. 2008 Retrovirology Method HIV A179P;V165P 87;80 92;85 IN;IN;IN 38;64;136 40;66;138 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. To test the effects of different IN mutants on viral infection, cDNAs encoding the IN mutants, including V165A, A179P, KR186,7AA or D64E, were introduced into the SVCMV-Vpr-RT-IN expressor by PCR-based method as described before. 2008 Retrovirology Method HIV A179P;D64E;V165A 112;132;105 117;136;110 Vpr;IN;IN;IN;RT 169;33;83;176;173 172;35;85;178;175 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. An expression construct for HIV-1 IN 1-288 residues (p28bIN-3CS-F185H) was also obtained from the laboratory of Dr. 2009 Journal of molecular biology Method HIV F185H 64 69 IN 34 36 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. The IN sequence encodes 4 substitutions (C56S, C65S, C280S, and F185H) to increase solubility and a six amino acid His-tag separated from the N-terminus of IN by a thrombin cleavage site. 2009 Journal of molecular biology Method HIV C280S;C56S;C65S;F185H 53;41;47;64 58;45;51;69 IN;IN 4;156 6;158 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. The resulting plasmid, pGEMPAC-SphALQYLA, was used to change the leucine at position 148 to an alanine using oligonucleotides (sense strand shown) 5'-ACCAGGTACCAGCCGCACAGTACTTAGCAC-3' and the Quick- Change Mutagenesis Kit (Stratagene) according to the manufacturer's instructions. 2009 Virology Method HIV L148A 65 102 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. The serine to alanine substitution at position 147 of Vif was introduced using oligonucleotides (only sense strand shown) 5'-AAGTACCAGGTACCAGCCCTACAGTACTTA-3' and the Quick-Change Mutagenesis Kit (Stratagene) according to the manufacturer's instructions. 2009 Virology Method HIV S147A 4 50 Vif 54 57 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Multiple lines for each TG were previously generated for native TK2 TG, TK2 mutant (H121N and I212N) TGs and Y955C pol-gamma mutant TG. 2009 Laboratory investigation; a journal of technical methods and pathology Method HIV H121N;I212N;Y955C 84;94;109 90;99;114 Pol 115 118 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. NVP-R was defined by mutations present at the following amino acid sites: L100I, K101E/P, K103N/S, V106A/M, V108I, Y181C/I/V, Y188C/L/H, or G190A/S/E based on recommendations from International AIDS Society-USA Drug Resistance Mutations and Stanford University drug-resistance database. 2009 PloS one Method HIV G190A;G190E;G190S;K101E;K101P;K103N;K103S;L100I;V106A;V106M;V108I;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 140;140;140;81;81;90;90;74;99;99;108;115;115;115;126;126;126 149;149;149;88;88;97;97;79;106;106;113;124;124;124;135;135;135 AIDS 194 198 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. The mutant IBD is the Asp366Asn version of the former. 2009 PloS one Method HIV D366N 22 31 Asp 22 25 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. The peptides HTHi and wt HTHi reproduce the sequences of the HTHi motifs in the IN-Phe185Lys variant and in wt IN respectively. 2009 PloS one Method HIV F185K;I185K;N185K 83;83;83 92;92;92 IN;IN 80;111 82;113 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. F12 harbors these mutations together with the G140S/Q148H double mutation in the F4 background. 2009 Nucleic acids research Method HIV G140S;Q148H 46;52 51;57 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In parallel, the E92Q, G140S, Q148H, N155H and G140S/Q148H mutations were obtained by site-directed mutagenesis from pET-15b, containing the WT sequence. 2009 Nucleic acids research Method HIV E92Q;G140S;G140S;N155H;Q148H;Q148H 17;23;47;37;30;53 21;28;52;42;35;58 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The F4 polymorphism consists of eight mutations with respect to the 'laboratory' WT pNL43 IN: K7Q, E11D, L101I, K127R, I135V, I200L, V201I, I220L. 2009 Nucleic acids research Method HIV E11D;I135V;I200L;I220L;K127R;K7Q;L101I;V201I 99;119;126;140;112;94;105;133 103;124;131;145;117;97;110;138 IN 90 92 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The introduction of the entire sequence of the IN gene with the G140S/Q148H mutation from the patient into the pNL43 context did not result in a productive infection, suggesting that other viral proteins of the patient were required for efficient replication (data not shown). 2009 Nucleic acids research Method HIV G140S;Q148H 64;70 69;75 IN 47 49 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We studied the E92Q, G140S, Q148H, N155H and G140S/Q148H mutations in a pNL43 background. 2009 Nucleic acids research Method HIV E92Q;G140S;G140S;N155H;Q148H;Q148H 15;21;45;35;28;51 19;26;50;40;33;56 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. All pretreatment plasma (viral RNA) and cell pellet (proviral DNA) samples were tested for the presence of the K103N mutation by allele-specific real-time PCR (AS-PCR). 2009 Clinical infectious diseases Method HIV K103N 111 116 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. PCR products were tested for the K103N mutation as described elsewhere. 2009 Clinical infectious diseases Method HIV K103N 33 38 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. The genotype was determined for samples with the K103N mutation by population sequencing. 2009 Clinical infectious diseases Method HIV K103N 49 54 19149765 Analysis and characterization of dimerization inhibition of a multi-drug-resistant human immunodeficiency virus type 1 protease using a novel size-exclusion chromatographic approach. PRT26A (autoproteolysis-resistant and monomeric HIV-1 PR) T26A (N15-labelled) monomeric PR was a gift from Dr John Louis [NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases), NIH (National Institutes of Health), Bethesda, MD, U.S.A.] and refolded as described previously. 2009 The Biochemical journal Method HIV T26A 56 62 PR;PR;PR 0;54;88 2;56;90 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Mutant DNA constructs K65R and K65R+M184V were generated by Quick-change Mutagenesis Kit (Strategene). 2009 Retrovirology Method HIV K65R;K65R;M184V 22;31;36 26;35;41 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Polymorphisms within subtype C RT differ from subtype B as follows: V35T, T39E, S48T, K166R, K173T, D177E, T200A, Q207E, R211K, L214F, V245K, T286A, E291D, I293V, R356K, G359T, T376A, T377Q, K390R, T403A, E404D, V435P, A437V, N460D, V466I, T468S, D471E, Y483Q, L491S, Q512K, K527Q, K530R, A534S. 2009 Retrovirology Method HIV A437V;A534S;D177E;D471E;E291D;E404D;G359T;I293V;K166R;K173T;K390R;K527Q;K530R;L214F;L491S;N460D;Q207E;Q512K;R211K;R356K;S48T;T200A;T286A;T376A;T377Q;T39E;T403A;T468S;V245K;V35T;V435P;V466I;Y483Q 219;289;100;247;149;205;170;156;86;93;191;275;282;128;261;226;114;268;121;163;80;107;142;177;184;74;198;240;135;68;212;233;254 224;294;105;252;154;210;175;161;91;98;196;280;287;133;266;231;119;273;126;168;84;112;147;182;189;78;203;245;140;72;217;238;259 RT 31 33 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Subtype B RTs containing mutations K65R and K65R+M184V were generated as described previously. 2009 Retrovirology Method HIV K65R;K65R;M184V 35;44;49 39;48;54 RT 10 13 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Using the same gel-based system as described, we evaluated the efficiency of initiation of (-)ssDNA synthesis by subtype C WT RT and mutant RTs harboring mutations K65R and K65R/M184V. 2009 Retrovirology Method HIV K65R;K65R;M184V 164;173;178 168;177;183 RT;RT 126;140 128;143 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. After washing plates three times with PBST, 0.5-log10 serial dilutions of CV-N, m4-CVN, P51G-m4-CVN monomer and dimer to a final concentration in the 0.01 muM to 1 iM range were added to triplicate wells (100 mul/well) and incubated for 1 h. 2009 Biopolymers Method HIV P51G 88 92 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Binding of wt CV-N, S52P-m4-CVN, and DeltaQ50-m4-CVN to glycosylated soluble gp120 was assessed by ELISA as previously described. 2009 Biopolymers Method HIV S52P 20 24 gp120 77 82 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Construction of DeltaQ50-m4-CVN and S52P-m4-CVN Plasmids. 2009 Biopolymers Method HIV S52P 36 40 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. DeltaQ50-m4-CVN and S52P-m4-CVN plasmids were transformed by heat pulse into E. 2009 Biopolymers Method HIV S52P 20 24 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Expression and Purification of DeltaQ50-m4-CVN and S52P-m4-CVN. 2009 Biopolymers Method HIV S52P 51 55 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Melting temperatures for DeltaQ50-m4-CVN and S52P-m4-CVN primers are 73.8 C and 75 C, respectively. 2009 Biopolymers Method HIV S52P 45 49 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Oligomerization STATE of DeltaQ50-m4-CVN and S52P-m4-CVN. 2009 Biopolymers Method HIV S52P 45 49 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The anti-HIV activity of DeltaQ50-m4-CVN and S52P-m4CVN was evaluated using a modified XTT assay, using wt CV-N and P51G-m4-CVN as controls. 2009 Biopolymers Method HIV P51G;S52P 116;45 120;49 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The constructs used in this study (S52P-m4-CVN, DeltaQ50-m4-CVN, and wt CV-N) contained a eight amino acid sequence attached to the C terminus (LEHHHHHH), which comprises the His-tag. 2009 Biopolymers Method HIV S52P 35 39 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The forward/reverse primers for DeltaQ50 and S52P are as follows: . 2009 Biopolymers Method HIV S52P 45 49 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The forward/reverse primers for DeltaQ50 and S52P are as follows. 2009 Biopolymers Method HIV S52P 45 49 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The oligomerization state of AQ50-m4-CVN and S52P-m4-CVN proteins was determined by size-exclusion chromatography on a Superdex peptide 10/300 GL high-performance column. 2009 Biopolymers Method HIV S52P 45 49 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The starting point of cloning DeltaQ50-m4-CVN and S52P-m4-CVN genes is m4-CVN plasmid, which was constructed by sequentially introducing mutations into the pET-26b(+) (wt CV-N) background (Novagen). 2009 Biopolymers Method HIV S52P 50 54 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. To construct DeltaQ50-m4-CVN and S52P-m4-CVN plasmids, mutations were introduced into m4-CVN vector by using QuikChange II site-directed mutagenesis kit (Stratagene) with forward/reverse primers. 2009 Biopolymers Method HIV S52P 33 37 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. A second genotyping performed one month after HAART showed K101E, G190A, and T215F. 2009 PloS one Method HIV G190A;K101E;T215F 66;59;77 71;64;82 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Analyses for the M50-P50 sequences were performed with and without codon 101 to avoid the effect of convergent evolution of the K101E substitution. 2009 PloS one Method HIV K101E 128 133 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Another test performed 13 months after HAART initiation revealed the persistence of G190A and K101E and the accumulation of various NRTI mutations (Table 1). 2009 PloS one Method HIV G190A;K101E 84;94 89;99 NRTI 132 136 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Her baseline genotyping test before ARV therapy showed the K101E RT mutation. 2009 PloS one Method HIV K101E 59 64 RT 65 67 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. In order to evaluate whether the NNRTI primary mutation, G190A, was already presented in the child's quasispecies before the introduction of ARV, we analyzed the child's sample before the initiation of therapy. 2009 PloS one Method HIV G190A 57 62 NNRTI 33 38 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. First, to remove and replace the cleavage site mutations (A431V, I437V) of the patient-derived Gag-PR-RT fragment with the wild type pNL4-3 amino acid pattern and second, to add these mutations in the recombinant viruses containing the patient-derived PR-RT fragment. 2009 PLoS pathogens Method HIV A431V;I437V 58;65 63;70 Gag;PR;PR;RT;RT 95;99;252;102;255 98;101;254;104;257 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. Because of sequence polymorphisms, 5 samples could not be analyzed for the Y181C mutation, and 4 samples could not be analyzed for the G190A mutation. 2009 The Journal of infectious diseases Method HIV G190A;Y181C 135;75 140;80 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. One discrepancy between allele-specific PCR and LigAmp analysis was noted for 1 woman (LT2049) in whom a low level of K103N-resistant virus was detected by LigAmp analysis but not by allele-specific PCR. 2009 The Journal of infectious diseases Method HIV K103N 118 123 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. To confirm results of LigAmp analysis, real-time allele-specific PCR was performed to identify the K103N resistance mutation in plasma samples from South Africa; 0.5 mL of plasma was used for this analysis in accordance with the method described elsewhere. 2009 The Journal of infectious diseases Method HIV K103N 99 104 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. An analogous assay was performed using a variant strain of the virus that encodes the Y181C mutant form of HIV-RT. 2009 Journal of chemical information and modeling Method HIV Y181C 86 91 RT 111 113 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Additionally, K101E and G190E were also included as NNRTI mutations. 2009 AIDS (London, England) Method HIV G190E;K101E 24;14 29;19 NNRTI 52 57 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Factors associated with the emergence of K65R and K70E, pan-nucleoside resistance mutations (69 insertion, Q151M complex with K65R and K70E), and the presence of three or more TAM mutations were evaluated using logistic regression. 2009 AIDS (London, England) Method HIV K65R;K65R;K70E;K70E;Q151M 41;126;50;135;107 45;130;54;139;112 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. NNRTI mutations included K103N, Y181C, Y181I, G190A, G190S, V108I, Y188L, V106M, P225H, and K103NS. 2009 AIDS (London, England) Method HIV G190A;G190S;K103N;K103N;K103S;P225H;V106M;V108I;Y181C;Y181I;Y188L 46;53;25;92;92;81;74;60;32;39;67 51;58;30;98;98;86;79;65;37;44;72 NNRTI 0 5 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. NRTI mutations included K65R and K70E (associated with TDF resistance), thymidine analog mutations (TAMs) M41L, D67N, K70R, L210W, T215Y, T215F, K219Q, and K219E, and multinucleoside mutations, including the 69 insertion complex and the 151 complex. 2009 AIDS (London, England) Method HIV D67N;K219E;K219Q;K65R;K70E;K70R;L210W;M41L;T215F;T215Y 112;156;145;24;33;118;124;104;138;131 116;161;150;28;37;122;129;110;143;136 NRTI 0 4 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Samples with M184V, M184I, and M184V/I were considered to have 3TC and emtricitabine (FTC) resistance. 2009 AIDS (London, England) Method HIV M184I;M184I;M184V;M184V 31;20;13;31 38;25;18;38 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Virus with 69 insertion or Q151M complex with K65R or K70E were considered pan-nucleoside resistant by genotype. 2009 AIDS (London, England) Method HIV K65R;K70E;Q151M 46;54;27 50;58;32 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. The SYBYL and O programs were used to prepare molecular model of the complexes of HIV-1 RT in complex with RNA/DNA (Protein Data Bank code number 1HYS), and containing mutations A376S, N348I and Q509L that were introduced manually into the original 1HYS structure. 2009 Antiviral research Method HIV A376S;N348I;Q509L 178;185;195 183;190;200 RT 88 90 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Allele-Specific PCR to Detect K103N and Y181C Mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 30;40 35;45 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Construction of Wild Type, K103N, and Y181C RNA Standards. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 27;38 32;43 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Each RT-PCR was performed in 25 muL with final reagent concentrations of 4 ng/muL each of primers RT1 and RT4 or RT18 and RT21 and 1x Reaction Mix (Invitrogen) to which 0.5 muL SuperScript III RT/Platinum Taq mix (Invitrogen) and 5 muL of either extracted viral RNA, no-template controls, or RNA standards (either K103N, Y181C, or wild type) were added. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 314;321 319;326 RT;RT;RT;RT;RT;RT 5;98;106;113;122;193 7;100;108;115;124;195 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. For allele-specific amplification, the forward primer was the same as for total HIV copy PCR, but the reverse primer was replaced by K103N-rev-mut (5'-CCACATCCAGTACTGTTACTGATTTG-3') for amplification of K103N mutants and replaced by Y181C-Q23-2-sm (5'-ACATACAAGTCATCCATGTATTGAC-3') for amplification of Y181C mutants. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;K103N;Y181C;Y181C 133;203;233;303 138;208;238;308 Rev 139 142 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Parallel reactions of total HIV copy, K103N allele-specific, and Y181C allele-specific real-time PCR were performed on the same first-round PCR product using SYBR green detection on an ABI prism 7900HT. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 38;65 43;70 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Subsequently, site-directed mutagenesis was performed to independently introduce K103N (AAC) and Y181C (TGT). 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 81;97 86;102 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. The proportion of drug-resistant virus was calculated for each reaction, and if it was below the lower limit of the assay (0.2% for K103N and 2% for Y181C. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 132;149 137;154 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. The quantities of total and drug-resistant HIV copies was estimated by comparing the cycle threshold values of samples of interest with those from 104 to 10-1 copies per microliter serial dilutions of either wild type, K103N, or Y181C standard RNA template. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 219;229 224;234 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Wild type, K103N, or Y181C RNA standards were quantified by ultraviolet spectroscopy diluted to 104 copies per microliter in carrier RNA and stored at -80 C until use. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;Y181C 11;21 16;26 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. First, the template plasmid, Q77R p98CN009.8, was amplified using 2 PCR reactions with the four primers listed in Table 5 . 2009 PloS one Method HIV Q77R 29 33 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. The Q77R amino acid substitution was constructed using PCR amplification with primers encoding the mutation listed in Table 4 . 2009 PloS one Method HIV Q77R 4 8 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. The pNL4-3-DeltaE-EGFP based mutants (Y271A, G273A, I274A, K275A, V276A, R277A) and pLAI2 based mutants (Y271A and I274A) were constructed by site-directed mutagenesis using QuikChange II XL Site-Directed Mutagenesis Kit (Stratagene, USA) according to manufacturer's instruction. 2009 PloS one Method HIV G273A;I274A;I274A;K275A;R277A;V276A;Y271A;Y271A 45;52;115;59;73;66;38;105 50;57;120;64;78;71;43;111 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Clinical data on each patient with the K65R mutation was recorded from standardized electronic forms which capture demographic, clinical, laboratory and therapeutic information at baseline and at each visit. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R 39 43 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Finally, we describe immunologic and virologic outcomes among patients with the K65R mutation, who were switched to second line ART. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R 80 84 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. We also compared genotypic mutation patterns among patients with and without the K65R mutation and among patients with the K65R mutation on standard first line ART which did not contain TDF to those on TDF-containing first line ART. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R;K65R 81;123 85;127 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. We describe HIV-1 subtype and drug resistance mutation characteristics in a cohort of eligible patients and further characterize nucleoside reverse transcriptase inhibitor (NRTI) mutations in the subset with the K65R mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R 212 216 NRTI;NRTI 129;173 161;177 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Etravirine-resistance mutations were defined as mutations associated in the DUET studies with a decreased virological response to etravirine: V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S, and M230L. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV A98G;E138A;G190A;G190S;K101E;K101H;K101P;L100I;M230L;V106I;V179D;V179F;V179T;V90I;Y181C;Y181I;Y181V 148;179;208;208;161;161;161;154;221;172;186;186;186;142;197;197;197 152;184;215;215;170;170;170;159;226;177;195;195;195;146;206;206;206 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. L100I, K101E/P, K103N/S, V106A/M, Y181C/I/V, V179F, Y188C/H/L, G190A/S/E/Q and M230L were defined as major NNRTI resistance mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV G190A;G190E;G190Q;G190S;K101E;K101P;K103N;K103S;M230L;V106A;V106M;V179F;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L;L100I 63;63;63;63;7;7;16;16;79;25;25;45;34;34;34;52;52;52;0 74;74;74;74;14;14;23;23;84;32;32;50;43;43;43;61;61;61;5 NNRTI 107 112 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Patient samples were characterized according to the following criteria: (i) presence of the RT mutation K103N, (ii) ARV treatment history, (iii) plasma HIV-1 RNA level and (iv) availability of a cryopreserved sample. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N 104 109 RT 92 94 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Samples with acquired and transmitted K103N were studied only if they lacked other major NNRTI resistance mutations or known etravirine-resistance mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N 38 43 NNRTI 89 94 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The mutations V90I, A98G, V106I, E138A, and V179D/T were considered to be less important indicators of etravirine resistance because they are polymorphic (particularly V90I and V106I) and have not been shown to have a phenotypic effect on etravirine susceptibility. 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV A98G;E138A;V106I;V106I;V179D;V179T;V90I;V90I 20;33;26;177;44;44;14;168 24;38;31;182;51;51;18;172 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Two types of samples meeting study criteria were identified: (i) samples from ARV-naive patients containing the K103N mutation ("transmitted K103N") and (ii) samples obtained from patients receiving a failing NNRTI-containing regimen ("acquired K103N"). 2009 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;K103N;K103N 141;245;112 146;250;117 NNRTI 209 214 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Crystals of K65R RT dsDNA dATP were obtained by soaking the crystals of K65R RT dsDNA TFV-DP in the well solution containing 10 mm dATP for 10 min. 2009 The Journal of biological chemistry Method HIV K65R;K65R 12;72 16;76 RT;RT 17;77 19;79 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Crystals of K65R RT dsDNA TFV-DP complex were stabilized in crystallization buffer containing 12% polyethylene glycol 8000 and then cryoprotected by dipping in the respective transfer solution containing 25% glycerol for ~5 s and cryocooled in liquid N2. 2009 The Journal of biological chemistry Method HIV K65R 12 16 RT 17 19 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Cycles of model building and refinement using one of the three data sets yielded the final structure of K65R RT dsDNA TFV-DP (Table 1). 2009 The Journal of biological chemistry Method HIV K65R 104 108 RT 109 111 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. For the biochemical studies, wild-type and K65R mutant heterodimeric p66/p51 HIV-1 RT were expressed and purified as described. 2009 The Journal of biological chemistry Method HIV K65R 43 47 RT 83 85 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R HIV-1 RT was expressed in Escherichia coli and purified, as reported earlier. 2009 The Journal of biological chemistry Method HIV K65R 0 4 RT 11 13 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Pre-steady state constants (kpol) were determined using dATP (Roche Applied Science) or dATP-alpha-S (Sp isomer) (Biolog, Bremen, Germany) at 5 times the Kd value (200 mum for wild-type RT and 75 mum for K65R RT) and 100 nm active wild-type or K65R RT with a KinTek rapid quench-flow apparatus as described. 2009 The Journal of biological chemistry Method HIV K65R;K65R 204;244 208;248 RT;RT;RT 186;209;249 188;211;251 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The 27:20-mer dsDNA was cross-linked to K65R RT at the p66 C258 site, the cross-linked primer was extended with a dideoxy-G at the 3'-end through RT polymerization, the cross-linked K65R RT dsDNA complex was purified using Ni2+-nitrilotriacetic acid and heparin columns in tandem, and the purified complex was concentrated to ~10 mg/ml. 2009 The Journal of biological chemistry Method HIV K65R;K65R 40;182 44;186 RT;RT;RT 45;146;187 47;148;189 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The coordinates and structure factors for the crystal structures of K65R mutant RT dsDNA TFV-DP and K65R mutant RT dsDNA dATP complexes are available from the Protein Data Bank with accession codes 3JSM and 3JYT, respectively. 2009 The Journal of biological chemistry Method HIV K65R;K65R 68;100 72;104 RT;RT 80;112 82;114 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The DNA 19-mer primer (5'-GTCCCTGTTCGGGCGCCAC) and 36-mer template D36A (5'-TCTCTATGTGTGGCGCCCGAACAGGGACCTGAAAGC) were used in the study. 2009 The Journal of biological chemistry Method HIV D36A 67 71 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R mutation is present on the p66 subunit only, which also contains a mutation Q258C for cross-linking with the nucleic acid. 2009 The Journal of biological chemistry Method HIV K65R;Q258C 4;85 8;90 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R RT dsDNA dATP complex was obtained by soaking the crystals of K65R RT dsDNA TFV-DP in crystallization solution containing 10 mm dATP for 10 min. 2009 The Journal of biological chemistry Method HIV K65R;K65R 4;71 8;75 RT;RT 9;76 11;78 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R RT dsDNA model from the K65R RT dsDNA TFV-DP structure was used to determine the structure of the K65R RT dsDNA dATP complex. 2009 The Journal of biological chemistry Method HIV K65R;K65R;K65R 4;33;107 8;37;111 RT;RT;RT 9;38;112 11;40;114 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R RT dsDNA sample was co-crystallized with TFV-DP by hanging drop vapor diffusion against the well solution containing 50 mm Bistris propane, pH 6.4, 100 mm ammonium sulfate, 5% (v/v) glycerol, 5% (w/v) sucrose, 10% (w/v) polyethylene glycol 8000, and 20 mm MgCl2 (or MnCl2). 2009 The Journal of biological chemistry Method HIV K65R 4 8 RT 9 11 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The mutation C280S is present in both subunits. 2009 The Journal of biological chemistry Method HIV C280S 13 18 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Three different data sets, each to 3 A resolution, were collected from three crystals of K65R RT dsDNA TFV-DP; two crystals grew in the presence of MgCl2, and one grew in the presence of MnCl2. 2009 The Journal of biological chemistry Method HIV K65R 89 93 RT 94 96 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. An HIV-1 protease construct containing five mutations that retard autoproteolysis and avoid cysteine-thiol oxidation (Q7K, L33I, L63I, C67A and C95A), termed PR, was used. 2010 Proteins Method HIV C67A;C95A;L33I;L63I;Q7K 135;144;123;129;118 139;148;127;133;121 PR;PR 9;158 17;160 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. The G86A and G86S mutations were introduced into the PR template to generate PRG86A and PRG86S, respectively, using the QuikChange mutagenesis protocol (Stratagene, La Jolla, CA). 2010 Proteins Method HIV G86A;G86S 4;13 8;17 Capsid;PR;PR;PR 175;53;77;88 177;55;79;90 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. The V7I and I34L were both found to be significant in this study even though they missed the adjusted p value cutoff in the previous study. 2010 Journal of immunological methods Method HIV I34L;V7I 12;4 16;7 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Bar graphs were used to display the accumulation of mutations (any NNRTI, M184V/I, or any TAM) at detection of viremia and at 6, 12, and 18 months of persistent viremia on first-line cART for patients with multiple resistance tests at least one of which was >=12 months after first detection of viremia. 2009 Clinical infectious diseases Method HIV M184I;M184V 74;74 81;81 NNRTI 67 72 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Logistic regression was used to identify variables associated with the presence of i) NNRTI resistance and ii) the M184V/I mutation at first detection of viremia and to evaluate associations with resuppression within 6 months of detecting viremia among subjects with an HIV RNA result within this time frame. 2009 Clinical infectious diseases Method HIV M184I;M184V 115;115 122;122 NNRTI 86 91 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Thymidine associated mutations (TAMs) were M41L, D67N, K70R, L210W, T215Y/F, K219Q/E and multi-NRTI mutations included TAMS, K65R, and L74V. 2009 Clinical infectious diseases Method HIV D67N;K219E;K219Q;K65R;K70R;L210W;L74V;M41L;T215F;T215Y 49;77;77;125;55;61;135;43;68;68 53;84;84;129;59;66;139;47;75;75 NRTI 95 99 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. For M184V and K103N mutations, the multivariate analysis models were built using forward selection technique. 2010 AIDS (London, England) Method HIV K103N;M184V 14;4 19;9 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Mutant-specific primers ([HXB2:2319-2340] 5'-CTATTAGATACAGGAGCAAATA-3' for D30N; [HXB2:3078-3098] 5'- GACATAGTTATCTATCAATICG-3' for M184V; [HXB22884-2858] 5'-CCCACATCCAGTACTGTTACTGATTGG-3' for the K103N AAC allele; and [HXB22884-2858] 5'-CCACATCCAGTACTGTTACTGATTCA-3' for the K103N AAT allele) included the target codon in its 3' end and an intentional mismatch at positions -3 or -2, relative to the 3' end. 2010 AIDS (London, England) Method HIV D30N;K103N;K103N;M184V 75;197;276;132 79;202;281;137 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Non-specific primers ([HXB2:2319-2339] 5'-CTATTAGATACAGGAGCAGAT-3' for D30N; [HXB2:3078-3098] 5-GACATAGTTATCTATCAATAC-3' for M184V; and [HXB22884-2859] 5'-CCCACATCCAGTACTGTTACTGATTT-3 for both AAC and AAT K103N alleles) were similar to the former, but ended just before the target base pair and did not include intentional mismatches. 2010 AIDS (London, England) Method HIV D30N;K103N;M184V 71;205;125 75;210;130 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Odds of developing M184V or K103N were evaluated using the Generalized Estimating Equations model (SAS procedure GENMOD). 2010 AIDS (London, England) Method HIV K103N;M184V 28;19 33;24 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. The antiparallel primer ([HXB2:2592-2571] 5'-CTGGCTTTAATTTTACTGGTAC-3' for D30N; [HXB2:3277-3258] 5'-GGCTGTACTGTCCATTTATC-3' for M184V; and [HXB22757-2785] 5'-AAATGGAGAAAATTAGTAGATTTCAGAGA-3' for both AAC and AAT K103N alleles) was common for each pair of mutant-specific and non-specific reactions. 2010 AIDS (London, England) Method HIV D30N;K103N;M184V 75;213;129 79;218;134 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Variables associated with the selection of M184V, K103N and D30N mutations were investigated using Chi-square, Fisher's exact test or F-test, as needed. 2010 AIDS (London, England) Method HIV D30N;K103N;M184V 60;50;43 64;55;48 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Finally, Vpu mutants were constructed with the unmodified and corresponding L63A amino acid substitution in Vpu proteins from: a) subtype A2, strain 94CY017 (VpuSA2EGFPL64A); b)subtype B YU-2, (VpuSBYU-2EGFPL64A, initiation codon corrected); c) subtype C, strain BW16B01 (VpuSCEGFPL69A; d) subtype D, strain U88822 (VpuSDEGFPL64A) and e) subtype H, strain 90CR056 (VpuSHEGFPL63A). 2010 Virology Method HIV L63A 76 80 Vpu;Vpu 9;108 12;111 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. NRTI and non-NRTI (NNRTI) resistance mutations were analysed as per the current IAS-USA Drug Resistance Mutations group guidelines , except that NNRTI mutations solely associated with etravirine resistance were not included, and the non-IAS-USA-defined mutations D67G and S68 (any) and T215 reversion mutations were included in the analysis. 2010 The Journal of antimicrobial chemotherapy Method HIV D67G 263 267 NNRTI;NNRTI;NNRTI;NRTI 9;19;145;0 17;24;150;4 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. Inclusion criteria were as follows: (1) HIV-1 infected patients >18 years of age, (2) failed NNRTI-based antiretroviral therapy with M184V, thymidine analogue mutations (TAMs) and NNRTI-associated mutations and (3) had plasma HIV-1 RNA >1,000 copies/mL. 2009 AIDS research and therapy Method HIV M184V 133 138 NNRTI;NNRTI 93;180 98;185 HIV infections 40 54 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Four different C3d mutants were generated (C3d R162A, C3d D163A, C3d N170R and C3d D163A-N170R) using the next set of oligo primers: FRT880S 5'-atcgcactgcaggaagccgcggacatctgtgagggg-3', FRT881AS 5'cccctcacagatgtccgcggcttcctgcagtgcgat-3'(to generate C3d R162A); FRT882S 5'-ctgcaggaagccagggccatctgtgaggggcagatc-3', FRT883AS 5'-gatctgcccctcacagatggccctggcttcctgcag-3' (to generate C3d D163A); FRT884S 5'-tgtgaggggcaggtcagaagccttcctgggagc-3', FRT885AS 5'-gctcccaggaaggcttctgacctgcccctcaca-3' (to generate C3d R170R) (Table 1). 2010 Immunology letters Method HIV D163A;D163A;D163A;N170R;N170R;R162A;R162A;R170R 58;83;381;69;89;47;252;504 63;88;386;74;94;52;257;509 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. The double mutant (C3d D163A-N170R) was generated by introducing the N170R substitution on the initially generated C3d D163A. 2010 Immunology letters Method HIV D163A;D163A;N170R;N170R 23;119;29;69 28;124;34;74 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Site directed mutagenesis was utilized to introduce the S52A change in NL4-3 Vpu. 2010 Retrovirology Method HIV S52A 56 60 Vpu 77 80 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Splice overlap extension PCR was used to introduce mutation S52A in HIV-1 NL4-3 vpu and the element was subcloned by using the unique restriction sites StuI in env and the PflmI site just downstream of the pol gene, respectively. 2010 Retrovirology Method HIV S52A 60 64 Pol;Vpu;Env 206;80;160 209;83;163 20096702 A dynamic model of HIV integrase inhibition and drug resistance. During the first round of experiments with AutoDock4.0 that involved the four wild type targets and the ten targets of the G140S/Q148H mutant present in the QR2 subsets with a QH2 = 0.84, the charges on the magnesium ions and on the oxygen atoms of the DDE motif that coordinate them were derived from Quantum Mechanical simulations (QM) with Gaussian03. 2010 Journal of molecular biology Method HIV G140S;Q148H 123;129 128;134 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. A post-hoc analysis in the random cohort compared the mean change in viral load at day 14 on study from baseline in subjects with no NNRTI resistance mutations to subjects with low-abundant Y181C and to subjects with bulk resistance using the Wilcoxon rank sum test. 2010 The Journal of infectious diseases Method HIV Y181C 190 195 NNRTI 133 138 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Based on the random subcohort, the prevalence of baseline minority K103N and/or Y181C mutants was estimated; the prevalence of each minority variant was compared between virologic failures and non-failures using the Fisher's exact test. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 67;80 72;85 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Detection of K103N and Y181C mutants using allele-specific PCR. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 13;23 18;28 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. In a post-hoc analysis, all subjects with low-level Y181C mutants at baseline and experiencing virologic failure were evaluated for the presence of resistance by population sequencing at time of failure. 2010 The Journal of infectious diseases Method HIV Y181C 52 57 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Summary statistics of the demographics of subjects in the random subcohort by pre-existing minority K103N and/or Y181C mutants, population resistance, or no NNRTI resistance are described, as well as for additional subjects with virologic failure. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 100;113 105;118 NNRTI 157 162 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. The primary outcome measure for the case-cohort study was the occurrence of virologic failure; the primary variable of interest was presence or absence of minority K103N and/or Y181C variants in the pre-treatment samples. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 164;177 169;182 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. To identify pre-treatment minority K103N and Y181C variants, blinded pre-treatment plasma samples with no NNRTI resistance detected by population sequencing, were reanalyzed using ASPCR. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 35;45 40;50 NNRTI 106 111 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Using an exact test for homogeneity of odds ratios, the prevalence of Y181C mutants was compared between virologic failures and non-failures across the following subgroups: subjects with or without the K103N mutation, 4-drug or 3-drug EFV-based treatment, and screening HIV-1 RNA level. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 202;70 207;75 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Weighted Cox proportional hazards models were used to estimate the risk of virologic failure in the presence and absence of minority K103N and/or Y181C mutants at baseline among subjects without NNRTI resistance mutations by population sequencing. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 133;146 138;151 NNRTI 195 200 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. Allele-specific PCR was performed as published with the following modifications: 250-1800microl of plasma containing >=10,000 HIV-1 RNA copies were analyzed at codons 103 and 181 using 3 discriminatory primers for 3 different mutant alleles (AAC and AAT for K103N and TGT for Y181C). 2010 The Journal of infectious diseases Method HIV K103N;Y181C 258;276 263;281 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. For single-genome sequencing analyses, a total of 27 subjects (15 NNRTI-naive and 12 NNRTI-experienced) were randomly selected from enrollees meeting the following criteria: i) entry sample negative for NNRTI-resistance mutations by standard genotype analysis (ViroSeq platform; Celera, Alameda, CA); ii) reached a protocol-defined virologic failure endpoint by study week 24, and iii) the virologic failure sample had one or more major NNRTI-resistance mutations (L100I, K101E, K103N, V106A or M, V108I, Y181C or I, Y188C, H, or L, G190A or S, P225H, or P236L) detected by standard genotype (ViroSeq). 2010 The Journal of infectious diseases Method HIV G190A;K101E;K103N;L100I;P225H;P236L;V106A;V108I;Y181C;Y188C 533;472;479;465;545;555;486;498;505;517 538;477;484;470;550;560;491;503;510;522 NNRTI;NNRTI;NNRTI;NNRTI;Capsid 66;85;203;437;296 71;90;208;442;298 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. The association between NNRTI experience and the detection of K103N or Y181C was determined using a Fisher's exact test. 2010 The Journal of infectious diseases Method HIV K103N;Y181C 62;71 67;76 NNRTI 24 29 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In order to assess the incorporation of the Pr160Gag-Pol polyprotein precursor into recombinant virions, we also prepared a second set of HIV-1 clones containing the D25A inactivating mutation in the PR coding region to prevent proteolytic processing of Pr160Gag-Pol. 2010 Retrovirology Method HIV D25A 166 170 Pol;Pol;PR;PR;PR 53;263;44;200;254 56;266;46;202;256 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In our previous study, we used pSVC21-BH10 to prepare ten different variants mutated in the RT p51 RNH cleavage site (amino acid residues 437-443), namely A437I, V442S, F440W, F440V, T439S/V442G, Y441I/V442K, F440A, F440A/Y441A, F440W/Y441W, and E438N. 2010 Retrovirology Method HIV A437I;E438N;F440A;F440A;F440V;F440W;F440W;T439S;V442G;V442K;V442S;Y441A;Y441I;Y441W 155;246;209;216;176;169;229;183;189;202;162;222;196;235 160;251;214;221;181;174;234;188;194;207;167;227;201;240 RT 92 94 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. We introduced the mutation T477A into each of these p51 RNH cleavage site mutants as well as into the wild-type clone using the Quick Change Site-Directed Mutagenesis kit protocol (Stratagene, La Jolla, CA). 2010 Retrovirology Method HIV T477A 27 32 Capsid 204 206 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. The K103N, G190A, and Y181C NNRTI resistance mutations were tested using oligonucleotides designed for the CRF01_AE subtype prevalent in Thailand. 2010 Clinical infectious diseases Method HIV G190A;K103N;Y181C 11;4;22 16;9;27 NNRTI 28 33 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. The K70R, L74V, Y181C, M184V and N348I mutations were introduced into the wild-type (WT) p6HRT-Prot prokaryotic expression vector by site-directed mutagenesis using the QuikChange mutagenesis kit (Stratagene La Jolla, CA). 2010 AIDS (London, England) Method HIV K70R;L74V;M184V;N348I;Y181C 4;10;23;33;16 8;14;28;38;21 Capsid 218 220 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. The WT, K70R, Y181C, N348I, K70R/Y181C, K70R/Y181C/N348I, K70R/L74V, K70R/L74V/N348I, K70R/M184V, K70R/M184V/N348I HIV-1 RTs were purified as described previously. 2010 AIDS (London, England) Method HIV K70R;K70R;K70R;L74V;M184V;N348I;N348I;N348I;Y181C;K70R;K70R;K70R;K70R;L74V;M184V;N348I;Y181C;Y181C 40;69;98;74;103;51;79;109;45;8;28;58;86;63;91;21;14;33 44;73;102;78;108;56;84;114;50;12;32;62;90;67;96;26;19;38 RT 121 124 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. This refined gp41 model of the complete inner coiled-coil with the wildtype sequence then served as a master template for construction of L33Q, L33S, G36V, I37K, V38E, Q40H, and Q40K point mutations (3 a.a. 2010 Biochemistry Method HIV G36V;I37K;L33Q;L33S;Q40H;Q40K;V38E 150;156;138;144;168;178;162 154;160;142;148;172;182;166 gp41 13 17 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Multiple D21, D30, E34, E35 and F99 substitutions were introduced into a pGEX-3X derived plasmid expressing GST-p6pol-PRpse-FLAG H69E was generated in a previous report. 2010 Retrovirology Method HIV H69E 129 133 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The Quikchange II Multi-Site directed mutagenesis kit (Stratagene) was used to create the G680W reversion mutant and the constructs SVPC5-KGQI, SVPC5-KWKI, and SVPC5-NRQL. 2010 PloS one Method HIV G680W 90 95 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. Banked plasma-poor whole blood specimens collected from women immediately prior to initiating NVP-ART were retrospectively assessed for three HIV-1 pol mutations conferring high-level resistance to nevirapine (K103N, Y181C, and G190A). 2010 Clinical infectious diseases Method HIV G190A;K103N;Y181C 228;210;217 233;215;222 Pol 148 151 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. Two PCR-amplicons from each participant were evaluated in duplicate by OLA for mutations in three codons (K103N, Y181C and G190A) associated with resistance to NVP, using reagents adapted to HIV-1 CRF01_AE viruses. 2010 Clinical infectious diseases Method HIV G190A;K103N;Y181C 123;106;113 128;111;118 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. M230L was introduced into wild-type pNL4-3 using the primers: 5'-CCT TTG GCT GGG TTA TGA ACT CCA TC-3' (forward) and 5'-GAT GGA GTT CAT AAC CCA GCC AAA GG-3' (reverse). 2010 Virology Method HIV M230L 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Mutagenic primers were as follows: L74V, 5'-CAG TAC TAA ATG GAG AAA AGT AGT AGA TTT CAG AGA AC3' (forward) and 5' GTT CTC TGA AAT CTA CTA CTT TTC TCC ATT TAG TAC TG 3' (reverse); K101E, 5'-GCA GGG TTA GAA AAG AAA AAA TCA G-3' (forward) and 5'-CTG ATT TTT TCT TTT CTA ACC CTG C-3' (reverse); M41L, 5'-GCA TTA GTA GAA ATT TGT ACA GAA TTG GAA AAG GAA GG-3' (forward) and 5' CC TTC CTT TTC CAA TTC TGT ACA AAT TTC TAC TAA TGC-3' (reverse); and T215Y, 5'-GTG GGG ATT TTA CAC ACC AGA CAA AAA AC-3' (forward) and 5'-GT TTT TTG TCT GGT GTG TAA AAT CCC CAC-3' (reverse). 2010 Virology Method HIV K101E;L74V;M41L;T215Y 179;35;291;440 184;39;295;445 Gag 60 63 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. One stored sample identified as having K101E+G190S on bulk sequence was further evaluated. 2010 Virology Method HIV G190S;K101E 45;39 50;44 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The K101E+G190S and G190S mutants were also evaluated for EFV-dependent stimulation of replication using a modification of a previously published HIV replication fitness assay in which infected cells are detected by flow cytometry using antibodies directed against a virus-expressed Thy 1 reporter gene. 2010 Virology Method HIV G190S;G190S;K101E 10;20;4 15;25;9 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The K101E+G190S and G190S mutants were subcloned into the pAT2 vector, using silent XmaI and XbaI sites flanking reverse transcriptase, as previously described. 2010 Virology Method HIV G190S;G190S;K101E 10;20;4 15;25;9 RT 113 134 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The L74V, K101E, and M41L+T215Y mutations were introduced into pNL4-3XX containing wild-type or G190S RT sequences, as previously described. 2010 Virology Method HIV G190S;K101E;L74V;M41L;T215Y 96;10;4;21;26 101;15;8;25;31 RT 102 104 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Virus stocks derived by transient transfection of 293 cells were used to infect PM1 cells using inocula designed to give similar levels of replication in the no-drug control (5 ng p24 per million cells for G190S and 50 ng p24 per million cells for K101E+G190S). 2010 Virology Method HIV G190S;G190S;K101E 206;254;248 211;259;253 p24;p24 180;222 183;225 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Point mutations at SP1 residues 6-8 (SP1/6-8) were introduced into the infectious HIV-1 molecular clone pNL4-3 by using site-directed mutagenesis to generate pNL4-3 SP1-Q6A, Q6H, V7A, V7 M, T8A and T8Delta. 2010 Retrovirology Method HIV Q6H;T8A;V7A;V7M;Q6A 174;190;179;184;169 177;193;182;188;172 SP1;SP1;SP1 19;37;165 22;40;168 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. We followed-up the 50 mutations of resistance present at 32 positions: associated with in vitro or in vivo resistance to HIV-1 integrase inhibitors: H51Y, T66I/A/K, V72I, L74I/A/M, E92Q, T97A, T112I, F121Y, T125K, A128T, E138 K/A/D, G140R/C/H, Y143C/H/R, Q146K/P, S147G, Q148K/R/H, V151I, S153Y/A, M154I, N155S/H, K156N, E157Q, K160D/N, G163 R/K, V165I, V201I, I203M, T206S, S230N/R, V249I, R263K, C280Y. 2010 PloS one Method HIV A128T;C280Y;E138A;E138K;E157Q;E92Q;F121Y;G140C;G140H;G140R;G163K;G163R;H51Y;I203M;K156N;K160D;K160N;L74A;L74I;L74M;M154I;N155H;N155S;Q146K;Q146P;Q148H;Q148K;Q148R;R263K;S147G;S153A;S153Y;S230N;S230R;T112I;T125K;T206S;T66A;T66I;T66K;T97A;V151I;V165I;V201I;V249I;V72I;Y143C;Y143H;Y143R 214;398;221;221;321;181;200;233;233;233;337;337;149;361;314;328;328;171;171;171;298;305;305;255;255;271;271;271;391;264;289;289;375;375;193;207;368;155;155;155;187;282;347;354;384;165;244;244;244 219;403;231;231;326;185;205;242;242;242;345;345;153;366;319;335;335;179;179;179;303;312;312;262;262;280;280;280;396;269;296;296;382;382;198;212;373;163;163;163;191;287;352;359;389;169;253;253;253 IN 127 136 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Of these, L100I, K101P, Y181C/I/V and M230L were considered to be major etravirine RAMs based on their marked effect on etravirine susceptibility. 2010 The Journal of antimicrobial chemotherapy Method HIV K101P;L100I;M230L;Y181C;Y181I;Y181V 17;10;38;24;24;24 22;15;43;33;33;33 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The complete list of etravirine RAMs was defined as V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S and M230L. 2010 The Journal of antimicrobial chemotherapy Method HIV A98G;E138A;G190A;G190S;K101E;K101H;K101P;L100I;M230L;V106I;V179D;V179F;V179T;V90I;Y181C;Y181I;Y181V 58;89;118;118;71;71;71;64;130;82;96;96;96;52;107;107;107 62;94;125;125;80;80;80;69;135;87;105;105;105;56;116;116;116 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. These mutations included: (i) 46 non-polymorphic NNRTI-selected mutations at 28 positions (I94L, A98G, L100I, K101E/H/N/P, K102N, K103H/N/S/T, S105T, V106A/M, E138Q, T139R, I178F, V179F, Y181C/I/V, Y188C/H/L, G190A/C/E/Q/S, H221C/Y, K223T, P225H, F227L/Y, M230L, Y232H, L234I, P236L, D237E, K238N/T, V241M, Q242L and Y318F); and (ii) several polymorphic mutations that have been associated with decreased susceptibility to one or more NNRTIs (V108I) or are included in the etravirine resistance-associated mutations (RAMs) (V90I, V106I, E138A and V179D/T). 2010 The Journal of antimicrobial chemotherapy Method HIV A98G;D237E;E138A;E138Q;F227L;F227Y;G190A;G190C;G190E;G190Q;G190S;H221C;H221Y;I178F;I94L;K101E;K101H;K101N;K101P;K102N;K103H;K103N;K103S;K103T;K223T;K238N;K238T;L100I;L234I;M230L;P225H;P236L;Q242L;S105T;T139R;V106A;V106I;V106M;V108I;V179D;V179F;V179T;V241M;V90I;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L;Y232H;Y318F 97;284;537;159;247;247;209;209;209;209;209;224;224;173;91;110;110;110;110;123;130;130;130;130;233;291;291;103;270;256;240;277;307;143;166;150;530;150;443;547;180;547;300;524;187;187;187;198;198;198;263;317 101;289;542;164;254;254;222;222;222;222;222;231;231;178;95;121;121;121;121;128;141;141;141;141;238;298;298;108;275;261;245;282;312;148;171;157;535;157;448;554;185;554;305;528;196;196;196;207;207;207;268;322 NNRTI;NNRTI 49;435 54;441 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. We also examined the extent to which the 52 NNRTI-selected mutations covaried with mutations at 12 major nucleoside reverse transcriptase inhibitor (NRTI) resistance positions, including M41L, K65R, D67N, T69S_SS, K70E, K70R, L74V, L74I, V75M/T, Y115F, Q151M, M184V/I, L210W, T215F and T215Y. 2010 The Journal of antimicrobial chemotherapy Method HIV D67N;K65R;K70E;K70R;L210W;L74I;L74V;M184I;M184V;M41L;Q151M;T215F;T215Y;T69S;V75M;V75T;Y115F 199;193;214;220;269;232;226;260;260;187;253;276;286;205;238;238;246 203;197;218;224;274;236;230;267;267;191;258;281;291;209;244;244;251 NRTI;NNRTI;NRTI 105;44;149 137;49;153 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. We performed multidimensional scaling on the pairwise association data using a matrix D of dissimilarity coefficients (JD = 1 - J, where J is the Jaccard similarity coefficient) for the 22 mutations found in the significantly positively associated pairs (corrected P < 0.05): A98G, L100I, K101E, K101H, K101P, K102N, K103N, K103S, V106A, V106I, V106M, V108I, V179D, V179F, Y181C, Y188L, G190A, G190S, H221Y, P225H, F227L and K238T. 2010 The Journal of antimicrobial chemotherapy Method HIV A98G;F227L;G190A;G190S;H221Y;K101E;K101H;K101P;K102N;K103N;K103S;K238T;L100I;P225H;V106A;V106I;V106M;V108I;V179D;V179F;Y181C;Y188L 276;415;387;394;401;289;296;303;310;317;324;425;282;408;331;338;345;352;359;366;373;380 280;420;392;399;406;294;301;308;315;322;329;430;287;413;336;343;350;357;364;371;378;385 Matrix 79 85 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. To generate I309L mutations, PCR-directed site mutagenesis was performed using two overlapping primers that contained the mutated sequence for each Env using a strategy similar to that described in. 2010 Virology Method HIV I309L 12 17 Env 148 151 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Samples were available for 9/10 patients who had both M184V and K65R mutations detected by standard genotype, either with or without wild-type as a mixture. 2010 Antiviral therapy Method HIV K65R;M184V 64;54 68;59 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Briefly, recombinant HIV-1 virus-like particles (WT HIV-1(VSV-G) and S16A/P17A HIV-1(VSV-G)) were produced by cotransfection of 293T cells with pHCMV-G and pNL4-3Deltaenv or pNL4-3Deltaenv carrying the S16A/P17A mutation (pNL4-3Deltaenv(S16A/P17A)) as described in Ref. 2010 The Journal of biological chemistry Method HIV P17A;P17A;P17A;S16A;S16A;S16A 74;207;242;69;202;237 78;211;246;73;206;241 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Jurkat and CEM cells (1 x 105) were exposed to the HEK293 cell-derived WT virus or S16A/P17A variant (100 ng of p24 antigen) for 2 h at 37 C, washed with PBS(-), and cultured for 96 h. 2010 The Journal of biological chemistry Method HIV P17A;S16A 88;83 92;87 p24 112 115 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The mutant viruses (HIVNL4-3(S16A/P17A), HIVNL4-3DeltaenvWT, and HIVNL4-3Deltaenv(S16A/P17A)) were produced by the transient transfection of HEK293 cells using pNL4-3(S16A/P17A) or pNL4-3Deltaenv and pNL4-3Deltaenv(S16A/P17A) with the pNL4-3-based env expression vector. 2010 The Journal of biological chemistry Method HIV S16A;S16A;P17A;P17A;P17A;P17A;S16A;S16A 29;167;34;87;172;220;82;215 33;171;38;91;176;224;86;219 Env 248 251 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The overlayered gradient was then centrifuged at 100,000 x g in a Swing Rotor P65ST (HitachiKoki Co., Ltd.) for 2 h at 4 C. 2010 The Journal of biological chemistry Method HIV P65S;P65T 78;78 83;83 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The purified CA cores (2 ng) were resuspended in the uncoating assay buffer (50 mm NaH2PO4, pH 7.2, 150 mm NaCl, 200 mum sodium orthovanadate) and incubated with 0.114 mug/mul GST-Pin1, 0.114 mug/mul heat-denatured GST-Pin1, 0.114 mug/mul GST-Pin1 treated with juglone (molar ratio of GST-Pin1:juglone = 1:10; juglone was preincubated with GST-Pin1 at 37 C for 1 h and then removed by gel filtration) or 0.114 mug/mul GST-Pin1(W34A/K63A) at 37 C for 1 h. 2010 The Journal of biological chemistry Method HIV W34A;K63A 428;433 432;437 Capsid;PI;PI;PI;PI;PI;PI 13;180;219;243;289;344;423 15;182;221;245;291;346;425 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The relative percentage of disassembly efficiency (RPDE) is given by RPDE (%) = 100 x (CAS/CAT)/(CASC/CATC), where CAS is the concentration of the CA protein in the supernatant, CAT is the concentration of total CA protein in the supernatant plus pellet in the disassembly experiments of the CA core using boiled, juglone-treated GST-Pin1, or GST-Pin1(W34A/K63A); CASC is the concentration of the CA protein in the supernatant; and CATC is the concentration of total CA protein in the supernatant plus pellet in the control experiment using GST-Pin1. 2010 The Journal of biological chemistry Method HIV W34A;K63A 352;357 356;361 Capsid;Capsid;Capsid;Capsid;Capsid;Capsid;PI;PI;PI 115;147;212;292;397;467;334;347;545 117;149;214;294;399;469;336;349;547 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. To examine whether the infectivity defect of the S16A/P17A variant is linked to a dysfunction of uncoating, MAGIC-5 (4.5 x 106) cells were seeded in 60-cm2 flasks and the next day incubated with either 5 ml of WT HIV-1(VSV-G) or 5 ml of S16A/P17A HIV-1(VSV-G) incubated at 37 C for 4 h after 30 min of incubation at 4 C. 2010 The Journal of biological chemistry Method HIV P17A;P17A;S16A;S16A 54;242;49;237 58;246;53;241 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. The wild-type (WT), K103N, and Y181C HIV-1RTs (subtype B, LAI) were purified as described previously. 2010 Letters in drug design & discovery Method HIV K103N;Y181C 20;31 25;36 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. with the mutation K65R) in viruses from NRTI-treated individuals. 2010 PloS one Method HIV K65R 18 22 NRTI 40 44 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. For the ACT mutant, both mutated residues (V82T, I84V) have fewer atoms than the wild type. 2010 Journal of chemical theory and computation Method HIV I84V;V82T 49;43 53;47 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. We also used one-way ANOVA to test the differences in viral load among the T242X mutations with or without compensatory mutations in the HLA_B*57/*58-positive or -negative groups. 2010 PloS one Method HIV T242X 75 80 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Resultant constructs were designated G116E-GFP, 4/5S6/7S-GFP, and 4/5SG116E6/7S-GFP, respectively. 2010 Retrovirology Method HIV G116E 37 42 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Resultant constructs were designated NL-G116E and NL-G116EvifS, respectively (Figure 1). 2010 Retrovirology Method HIV G116E;G116E 40;53 45;58 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The differences in percent infection between WT-GFP and G116E-GFP, or 4/5S6/7S-GFP and 4/5SG116E6/7S-GFP were statistically evaluated by using the unpaired t test. 2010 Retrovirology Method HIV G116E 56 61 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The G116E substitution was also introduced into NL4-3 and NL-SVR (renamed NL-vifS in this report) by site-directed mutagenesis with the PCR-mediated overlap primer extension method. 2010 Retrovirology Method HIV G116E 4 9 Vif 77 80 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The structure of the N-terminal domain of the HIV-1 CA protein (PDB number 1GWP) was used as a template for building the domain model with the G116E substitution. 2010 Retrovirology Method HIV G116E 143 148 Capsid 52 54 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. To construct the lentivector expressing GFP under the control of cytomegalovirus promoter, we replaced the Eco RI-Apa I fragment corresponding to MA and CA of the pMDLg/p.RRE packaging vector with that of NL-G116E, and designated the resultant construct as pMDLg/p.RRE-G116E. 2010 Retrovirology Method HIV G116E;G116E 208;269 213;274 Matrix;Capsid 146;153 148;155 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. To construct the wild type and mutant HIV-1 clones expressing green fluorescence protein (GFP), the 1.3 kb BssHII-ApaI fragment of NL-G116E, NL-4/5S6/7SvifS, or NL-4/5SG116E6/7SvifS, which corresponds to the MA and CA, was transferred to NL-Nhe GFP, in which the env gene was interrupted; and the GFP gene was inserted into the nef region. 2010 Retrovirology Method HIV G116E 134 139 Nef;Env;Matrix;Capsid 328;263;208;215 331;266;210;217 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. To introduce a glycine (G)- to-glutamic acid (E) substitution at the 116th position of CA (G116E) into NL-4/5S6/7SvifS, the 0.5 kb SpeI-ApaI fragment, which corresponds to the N-terminus of the CA including the 116th position and L6/7, of pTopo-MA-CAd42 was transferred into NL-4/5S6/7SvifS to generate NL-4/5SG116E6/7SvifS. 2010 Retrovirology Method HIV G116E 91 96 Matrix;Capsid;Capsid;Capsid 245;87;194;248 247;89;196;250 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. The HIV-1 PR and mutants were constructed with five mutations Q7K, L33I, L63I, C67A, and C95A to prevent cysteine-thiol oxidation and diminish autoproteolysis. 2010 The FEBS journal Method HIV C67A;C95A;L33I;L63I;Q7K 79;89;67;73;62 83;93;71;77;65 PR 10 12 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Also it is unlikely that the delayed reverse transcription of the M184I mutant might eventually catch up to a WT level of the reverse transcription at later time points, because the preintegration (PIC) of HIV has a half-life of 1 day, Following imaging, HLFs were trypsinized and monitored for GFP expression by fluorescent activated cell sorting using the FL-1 channel of a FACS Caliber (Becton Dickinson). 2010 Virology Method HIV M184I 66 71 RT;RT 37;126 58;147 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Altering the ratio of WT and M184I RT packaged in a virion. 2010 Virology Method HIV M184I 29 34 RT 35 37 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. The M184I mutation was generated in a similar fashion as previously described. 2010 Virology Method HIV M184I 4 9 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. To produce vectors with varying concentrations of packaged RT, 293FT cells were transfected with the following amounts of WT (-) cPPT to M184I (-) cPPT vector DNA: 0:25, 2.5:22.5, 12.5:12.5, 22.5:2.5, and 25microg: 0microg. 2010 Virology Method HIV M184I 137 142 RT 59 61 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. The packaging plasmid pMDLg/pRRE was modified to introduce the D64V point mutation in the integrase encoding region through PCR-based mutagenesis. 2010 Vaccine Method HIV D64V 63 67 IN 90 99 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. The same protocol was employed to make the integration-deficient vectors except that the mutated pMDLg/pRRE containing the D64V point mutation was used for transfection. 2010 Vaccine Method HIV D64V 123 127 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. IN mutants N155H and Q148H were constructed in the pNY clone, expressed, and purified similar to wt IN. 2010 Biochemistry Method HIV N155H;Q148H 11;21 16;26 IN;IN 0;100 2;102 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. The G913A substitution was made to the pNL4-3 and the pNLDeltaSL1 vectors to generate pNL-913 and pNLDeltaSL1-913, respectively, by the QuikChange II XL Site-Directed Mutagenesis Kit (Agilent). 2010 Retrovirology Method HIV G913A 4 9 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. Using similar approach, the C1907T substitution was made to pNL4-3 and pNLDeltaSL1 to generate pNL-1907 and pNLDeltaSL1-1907, respectively. 2010 Retrovirology Method HIV C1907T 28 34 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The complete IN coding sequences of the 53 sequenced HIV-2 samples are available in Genbank under the accession numbers GU966535 through GU966581 group A and HM771234 through HM771239 for group B; the ROD-Q91R+I175M double mutant Genbank accession number is HM771240. 2010 Retrovirology Method HIV I175M;Q91R 210;205 215;209 IN 13 15 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. HIV (HXB2) viral stocks containing either the WT protease gene or mutations coding for single amino acid substitutions (I54V, V82A, or L90M) of the protease gene were produced as follows: Mutant PR coding sequences were generated from a pGEM vector containing the HIV-1 LAI (clone HXB2) PR and RT coding sequence, using the QuikChange Site-Directed Mutagenesis Kit (Stratagene, Foster City, CA) and high-performance liquid chromatography-purified primers (Genset Oligos). 2010 PLoS pathogens Method HIV I54V;L90M;V82A 120;135;126 124;139;130 PR;PR;Capsid;PR;PR;RT 49;148;391;195;287;294 57;156;393;197;289;296 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. K20R sense: 5'-GGGCAACTAAGGGAAGCTCTA-3', anti-sense: 5'-TAGAGCTTCCCTTAGTTGCCC-3'; D25G sense: 5'-AGGAAGCTCTATTAGGTACAGGAGCAGATGA-3', anti-sense: 5'-TCATCTGCTCCTGTACCTAATAGAGCTTCCT; T26S sense: 5'-GAAGCTCTATTAGATAGTGGAGCAGATGATACA-3'; anti-sense: 5'-TGTATCATCTGCTCCACTATCTAATAGAGCTTC-3'; I54V sense: 5'-GGAATTGGAGGTCTTATCAAAGTAAGA-3; anti-sense: 5'-TCTTACTTTGATAAGACCTCCAATTCC-3'; I54V sense: 5'-ATTGGAGGTTTTGTCAAAGTAAGACAG-3', anti-sense: 5'-CTGTCTTACTTTGACAAAACCTCCAAT-3'; L63P sense: 5'-GTAAGACAGTATGATCAGATACCCATAGAAATCTGTGGAC-3'; anti-sense: 5'-GTCCACAGATTTCTATGGGTATCTGATCATACTGTCTTAC-3'; V82A sense: 5'-GTAGGACCTACACCTGCCAACATAATTGGAAG-3'; anti-sense: CTTCCAATTATGTTGGCAGGTGTAGGTCCTAC-3'; L90M sense: 5'-TAATTGGAAGAAATCTGATGACTCAGATTGGTTG-3';and anti-sense: 5'-CAACCAATCTGAGTCATCAGATTTCTTCCAATTA-3'. 2010 PLoS pathogens Method HIV D25G;I54V;I54V;L63P;L90M;T26S;V82A;K20R 82;287;380;474;695;181;594;0 86;291;384;478;699;185;598;4 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. The PR mutants, L10I, K20R, D25G, T26S, D30N, I54V, L63P, V82A and L90M were created on the pEYFP-C1PR plasmid with the Quick-Exchange Site-directed Mutagenesis Kit (Stratagene, La Jolla, CA). 2010 PLoS pathogens Method HIV D25G;D30N;I54V;K20R;L10I;L63P;L90M;T26S;V82A 28;40;46;22;16;52;67;34;58 32;44;50;26;20;56;71;38;62 Capsid;PR 188;4 190;6 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Before ENF interruption, subjects P1, P2 and P3 were treated with ENF for 27, 33 and 39 weeks, respectively, and each of them had the V38A mutation as the predominant virus population (more than 85% frequency). 2010 PLoS computational biology Method HIV V38A 134 138 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Further, loss of V38A mutation at rate mur, can lead to any of a variety of viral variants that we include in the drug sensitive population. 2010 PLoS computational biology Method HIV V38A 17 21 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Lastly, virus variants carrying the V38A mutation may also carry other mutations, such as compensatory mutations or other drug resistance mutations, which may affect the fitness of the drug-resistant population as well as its level of drug resistance. 2010 PLoS computational biology Method HIV V38A 36 40 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Moreover, the data have taken only V38A mutants into account with other mutants being included in the "wild-type". 2010 PLoS computational biology Method HIV V38A 35 39 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. We obtained wild-type and V38A mutant viral load and CD4+ T cell data from Department of Medicine, University of California-San Francisco, CA, USA, San Francisco General Hospital, San Francisco, CA, USA and Section of Retroviral Therapeutics, Brigham and Women's Hospital and Division of AIDS, Harvard Medical School, Boston, MA, USA. 2010 PLoS computational biology Method HIV V38A 26 30 Matrix;Capsid;Capsid 326;139;195 328;141;197 AIDS 288 292 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Whether the V38A mutation in gp41 affects viral production remains unclear. 2010 PLoS computational biology Method HIV V38A 12 16 gp41 29 33 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. For all three cohorts, detection of the V75I mutation was performed using a highly sensitive OLA (http://depts.washington.edu/idimmweb/faculty/frenkel/OLAmanual1305april04.pdf) for HIV-1 subtypes A, B, C and D, developed using two differentially modified genotype-specific probes (5'-Digoxigenin-AYAGCACTAARTGGAGRAAATTAG-3' for wild-type, and 5'-Fluorescein-AYAGCACTAARTGGAGRAAATTAA-3' for mutant) and a biotin labeled common probe (5'-phosphate-TAGATTTYAGRGARCTCAATAAAAGA-Biotin-3'). 2011 The Journal of infectious diseases Method HIV V75I 40 44 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. Samples with OD values greater than or equal to the 2% mutant control were considered positive for a G to A mutation encoding V75I, while samples with negative reactions for both the mutant and wild-type genotypes were defined as "indeterminate," which implied genetic polymorphisms within 2-3 bases of the ligation site. 2011 The Journal of infectious diseases Method HIV V75I 126 130 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. for the resistance associated mutation M184V seventeen combinations VM and eight combinations MV were reported. 2010 PloS one Method HIV M184V 39 44 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Ideal helices of BST-2 (LLGIGILVLLIIVILGVPLIIF) and Vpu-WT (MVPIIVAIVA10 LVVAIIIAIV20 VWSIVIIEYR30 KI, GenBank: AAB59750.1, www.ncbi.nlm.nih.gov) and the mutant Vpu-A18H containing the TMDs of the respective proteins were created using integrated protein builder of MOE (www.chemcomp.com). 2011 Virology Method HIV A18H 165 169 Vpu;Vpu 52;161 55;164 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Modeling interaction potential of BST-2 and Vpu-A18H. 2011 Virology Method HIV A18H 48 52 Vpu 44 47 21248851 Atomic-level modelling of the HIV capsid. Soluble, disulfide-crosslinked pentamers of HIV-1NL4-3 CA (containing either N21C/A22C/W184A/M185A or P17C/R18L/T19C/W184A/M185A mutations) were prepared by sequential dialysis of purified protein. 2011 Nature Method HIV A22C;M185A;M185A;N21C;P17C;R18L;T19C;W184A;W184A 82;93;123;77;102;107;112;87;117 86;98;128;81;106;111;116;92;122 Capsid 55 57 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Homogenous populations of both double mutant viruses, K65R+L74V and K65R+L74I were produced in 293T cells. 2011 Virology journal Method HIV K65R;K65R;L74I;L74V 54;68;73;59 58;72;77;63 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In order to quantify reversion rates, various ratios of wild type cDNA (K65) and mutated K65R cDNA were mixed and sequenced; peak heights were measured for both nucleotides and percentage reversion was calculated according to our previously published protocols. 2011 Virology journal Method HIV K65R 89 93 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Mutagenic oligonucleotide pNL74I 5'-GAAATCTACTATTT TTCTCCAT-3' was used to create L74I mutation in the background of NL4-3 (wild type) and NL4-3 containing K65R mutation. 2011 Virology journal Method HIV K65R;L74I 156;82 160;86 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Mutants K65R, L74V, and K65R+L74V that have been previously analyzed for replication capacity and in vitro RT processivity were used as controls. 2011 Virology journal Method HIV K65R;K65R;L74V;L74V 8;24;14;29 12;28;18;33 RT 107 109 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Statistical analysis was conducted to determine the differences in processivity between WT and mutant viruses or among mutant viruses K65R+L74V and K65R+L74I during a single processivity cycle. 2011 Virology journal Method HIV K65R;K65R;L74I;L74V 134;148;153;139 138;152;157;143 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We have demonstrated previously that RT containing K65R+L74V is highly unstable and a rapid R K reversion occurs at RT codon 65. 2011 Virology journal Method HIV K65R;L74V 51;56 55;60 RT;RT 37;116 39;118 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. However one mouse in the V38E and WT group was lost at 2 and 4 weeks respectively during bleeding. 2011 Virology journal Method HIV V38E 25 29 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Total of four mice per group were infected with either WT or V38E virus. 2011 Virology journal Method HIV V38E 61 65 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Virus stocks were prepared with molecular clones of the WT virus or V38E mutant as described previously. 2011 Virology journal Method HIV V38E 68 72 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. WT virus contains the Lai ENV in NL4-3 backbone and the mutant V38E was generated by site directed mutagenesis and have been described previously. 2011 Virology journal Method HIV V38E 63 67 Env 26 29 21276267 Interplay between HIV entry and transportin-SR2 dependency. Plasmid pNL4-3 N74D CA was created by digesting pNL4-3.Luc.R-E- N74D CA with BssHII and SpeI and cloning this fragment into pNL4-3 digested with BssHII and SpeI. 2011 Retrovirology Method HIV N74D 64 68 Capsid;Capsid 20;69 22;71 21276267 Interplay between HIV entry and transportin-SR2 dependency. The construct pNL4-3.Luc.R-E- N74D CA encoding a N74D CA mutant reporter virus was a kind gift of Dr. 2011 Retrovirology Method HIV N74D;N74D 30;49 34;53 Capsid;Capsid 35;54 37;56 21276267 Interplay between HIV entry and transportin-SR2 dependency. We measured equal ratios of wild type and N74D mutant virus in both the pseudotyped and replication competent virus stocks using both the Innogenetics p24 ELISA and the RT activity kit. 2011 Retrovirology Method HIV N74D 42 46 p24;RT 151;169 154;171 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. Recombinant wt HIV IN (pNY strain) and IN possessing the single N155H drug-resistant mutation were used in this study. 2011 Journal of molecular biology Method HIV N155H 64 69 IN;IN 19;39 21;41 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The final list of mutations included M41L, E44D, D67N, T69D, K70R, L74V, L100I, K103N, V108I, V118I, Y181C, M184V, G190A, L210W, T215F, T215Y and K219Q in RT; and L33F, L33I, M46I, M46L, G48V, V82A, V82F, V82L, V82S, I84A, I84C, L90M in PR. 2011 PloS one Method HIV D67N;E44D;G190A;G48V;I84A;I84C;K103N;K219Q;K70R;L100I;L210W;L33F;L33I;L74V;L90M;M184V;M41L;M46I;M46L;T215F;T215Y;T69D;V108I;V118I;V82A;V82F;V82L;V82S;Y181C 49;43;115;187;217;223;80;146;61;73;122;163;169;67;229;108;37;175;181;129;136;55;87;94;193;199;205;211;101 53;47;120;191;221;227;85;151;65;78;127;167;173;71;233;113;41;179;185;134;141;59;92;99;197;203;209;215;106 PR;RT 237;155 239;157 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Group A: ATV and/or SQV (no selection pressure on L76V) 2011 AIDS research and therapy Method HIV L76V 50 54 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Group A: ATV and/or SQV (no selection pressure on L76V). 2011 AIDS research and therapy Method HIV L76V 50 54 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Group B: LPV or APV plus ATV or SQV (maintained selection pressure on L76V) 2011 AIDS research and therapy Method HIV L76V 70 74 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Group B: LPV or APV plus ATV or SQV (maintained selection pressure on L76V). 2011 AIDS research and therapy Method HIV L76V 70 74 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Group C: LPV or APV plus other drugs (maintained selection pressure on L76V) 2011 AIDS research and therapy Method HIV L76V 71 75 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Group C: LPV or APV plus other drugs (maintained selection pressure on L76V). 2011 AIDS research and therapy Method HIV L76V 71 75 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? HIV strains of 46 intensely pretreated (34 showed NRTI/NNRTI/PI resistance/12 showed NRTI/PI resistance) and one naive with transmitted mutation, L76V-positive patients derived from 24 centres throughout Germany between 1999-2009 were retrospectively analysed for HIV-resistance patterns and success of follow-up therapy. 2011 AIDS research and therapy Method HIV L76V 146 150 NNRTI;NRTI;NRTI;PI;PI 55;50;85;61;90 60;54;89;63;92 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? In this cohort, only patients with major L76V positive population were included. 2011 AIDS research and therapy Method HIV L76V 41 45 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Amino acid exchanges at Ser-40 in p6 were introduced by site-directed mutagenesis using oligonucleotides containing the indicated changes (S40F, DeltaYP, and DeltaPTAP) and the Quick Change site directed mutagenesis kit (Stratagene). 2011 Retrovirology Method HIV S40F 139 143 Gag 34 36 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Although mutation of either P72A or P75A would be expected to cripple Nef binding to a SH3 domain, these singly mutated Nefs only exhibit a partial loss of function. 2011 Journal of neuroimmune pharmacology Method HIV P72A;P75A 28;36 32;40 Nef;Nef 70;120 73;124 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. An early report that the R106L mutation prevented Nef from activating PAK2 was interpreted as this arginine being critical for PAK2 activation. 2011 Journal of neuroimmune pharmacology Method HIV R106L 25 30 Nef 50 53 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Another commonly used mutation, G2A, prevents myristoylation. 2011 Journal of neuroimmune pharmacology Method HIV G2A 32 35 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. As previously discussed subtype E Nefs have arginine at position 191 and introduction of F191R into the subtype B Nef from HIV-1SF2 debilitates PAK2 activation. 2011 Journal of neuroimmune pharmacology Method HIV F191R 89 94 Nef;Nef 34;114 38;117 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. At a minimum, the E160A mutation is also needed. 2011 Journal of neuroimmune pharmacology Method HIV E160A 18 23 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Based on the 99% conservation of R106, we tested the conservative mutation R106K as a more stringent test of the significance of this arginine for several Nef functions. 2011 Journal of neuroimmune pharmacology Method HIV R106K 75 80 Nef 155 158 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Doubt has been cast on a role for a SH3 binding protein in MHCI downregulation by studies with the CEM T cell line by comparing the AXXA mutation with the single mutations P72A, P75A, and P78A. 2011 Journal of neuroimmune pharmacology Method HIV P72A;P75A;P78A 172;178;188 176;182;192 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. F191I or F191A. 2011 Journal of neuroimmune pharmacology Method HIV F191A;F191I 9;0 14;5 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Finally, the fact that the EDAA mutation is phenotypically the same as D175E, is potentially useful for experimental systems where HIV-1 is replicating and capable of reverting point mutations. 2011 Journal of neuroimmune pharmacology Method HIV D175E 71 76 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Finally, the mutations of phenylalanine-191 to isoleucine (F191I) that was introduced as a specific mutation of PAK2 activation and aspartate-123 to glutamate (D123E) for investigating multiple Nef phenotypes will be discussed. 2011 Journal of neuroimmune pharmacology Method HIV D123E;D123E;F191I;F191I 160;132;59;26 165;158;64;57 Nef 194 197 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. For AAAA, AXXA, and R106A, phenotypic equivalence with conservative mutations is not the case and for M20A and for LLAA it has not been tested. 2011 Journal of neuroimmune pharmacology Method HIV M20A;R106A 102;20 106;25 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. For example D123G is completely defective for CD4 downregulation, MHCI downregulation, and enhancement of infectivity. 2011 Journal of neuroimmune pharmacology Method HIV D123G 12 17 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. For these reasons P72A, P75A, P78A and R77A mutations are preferred to the AXXA mutation for investigating the mechanism of MHCI downregulation. 2011 Journal of neuroimmune pharmacology Method HIV P72A;P75A;P78A;R77A 18;24;30;39 22;28;34;43 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Given the multiple defects exhibited by the R106L mutant, an alternate hypothesis is that there is a general disruption of Nef structure. 2011 Journal of neuroimmune pharmacology Method HIV R106L 44 49 Nef 123 126 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. In contrast to the R106A mutant which is inactive for PAK2 activation and enhancement of virion infectivity R106K is partially active for PAK2 activation and fully functional for enhancement of infectivity. 2011 Journal of neuroimmune pharmacology Method HIV R106A;R106K 19;108 24;113 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. In contrast,, assayed for the presence of dimers by intracellular cross-linking by formaldehyde and found no impact of mutating aspartate-123 to arginine on the level of Nef dimers. 2011 Journal of neuroimmune pharmacology Method HIV D123R 128 153 Nef 170 173 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. In the case of PAK2 activation, this has been done for P72A, P75A and R77E and indeed all of these singly mutated Nefs do completely lose their PAK2 activation capacity. 2011 Journal of neuroimmune pharmacology Method HIV P72A;P75A;R77E 55;61;70 59;65;74 Nef 114 118 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. It is also unclear why the R105E and R105E/R106E mutations do not completely disrupt dimerization as the pair of D123/R105 salt bridges in the dimerization model are converted to D123/E105. 2011 Journal of neuroimmune pharmacology Method HIV R105E;R105E;R106E 27;37;43 32;42;48 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. It would be expected that D123E would fail to block the enhanced Hck activation by the Nef/estrogen receptor hormone binding domain chimera, but the results of Walk et al suggest that this conservative mutation would block CD4 downregulation, MHCI downregulation, and PAK2 activation. 2011 Journal of neuroimmune pharmacology Method HIV D123E 26 31 Nef 87 90 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. M20A eliminated the ability of Nef to downregulate MHCI in infected CEM cells, but had no effect on CD4 downregulation or the infectivity of HIV-1 virions in single-round replication assays. 2011 Journal of neuroimmune pharmacology Method HIV M20A 0 4 Nef 31 34 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. made the remarkable observation that the D175E mutant displayed a severely reduced binding to the AP-2 gamma-sigma1 hemicomplex in the yeast three hybrid system (Y3H). 2011 Journal of neuroimmune pharmacology Method HIV D175E;Y3H 41;162 46;165 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Moreover, the conservative D123E mutant and the drastic D123R mutant have the exact same phenotype. 2011 Journal of neuroimmune pharmacology Method HIV D123E;D123R 27;56 32;61 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Nonetheless, the Nef mutant P78A fully abrogates MHCI downregulation. 2011 Journal of neuroimmune pharmacology Method HIV P78A 28 32 Nef 17 20 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Other striking mutations that abrogate MHCI downregulation that are discussed below are D123E and P78. 2011 Journal of neuroimmune pharmacology Method HIV D123E 88 93 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. R106A. 2011 Journal of neuroimmune pharmacology Method HIV R106A 0 5 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Similar to the R106A mutant, the R106K mutation was partially functional for CD4 downregulation and for MHCI downregulation. 2011 Journal of neuroimmune pharmacology Method HIV R106A;R106K 15;33 20;38 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Similarly, the P75A gave a 20 fold reduction in KD. 2011 Journal of neuroimmune pharmacology Method HIV P75A 15 19 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Since the Nef-Hck interaction has been described in great detail it is expected that P72A, P75A, R77A, but not P78A should cripple the MHCI signaling pathway. 2011 Journal of neuroimmune pharmacology Method HIV P72A;P75A;P78A;R77A 85;91;111;97 89;95;115;101 Nef 10 13 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Subsequently, internalization studies suggested that M20A resulted in enhanced recycling of MHCI at the plasma membrane. 2011 Journal of neuroimmune pharmacology Method HIV M20A 53 57 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The D123N, D123A, D123V, R105E, and R105E/R106E mutations decrease BiFC by 97%, 70%, 53%, 50%, and 71% respectively, but all of the aspartate mutations and the double arginine mutation are completely defective for CD4 downregulation and HIV-1 replication in modified U87MG astroglioma cells. 2011 Journal of neuroimmune pharmacology Method HIV D123A;D123N;D123V;R105E;R105E;R106E 11;4;18;25;36;42 16;9;23;30;41;47 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The designation, AXXA, refers to a double mutation of critical prolines in the SH3 binding domain of Nef (P72A/P75A). 2011 Journal of neuroimmune pharmacology Method HIV P72A;P75A 106;111 110;115 Nef 101 104 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The drastic mutations of V74D and R77E also obliterated binding. 2011 Journal of neuroimmune pharmacology Method HIV R77E;V74D 34;25 38;29 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The effort directed to the M20A mutation has been minimal relative to other mutations that negate MHCI downregulation. 2011 Journal of neuroimmune pharmacology Method HIV M20A 27 31 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The extreme mutation R106L is fully defective for MHCI and CD4 downregulation. 2011 Journal of neuroimmune pharmacology Method HIV R106L 21 26 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The F191I mutation is the most studied of the six mutations. 2011 Journal of neuroimmune pharmacology Method HIV F191I 4 9 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The finding of Wiskerchen and Cheng-Mayer that the P69A mutant of Nef does not activate PAK2 suggests an SH3 domain protein different from Hck is involved. 2011 Journal of neuroimmune pharmacology Method HIV P69A 51 55 Nef 66 69 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The KD's for these interactions have not been reported, and it remains to be determined if these proteins bind to Nef with the D175E mutation. 2011 Journal of neuroimmune pharmacology Method HIV D175E 127 132 Nef 114 117 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The phenotype of the R105E mutant was not tested. 2011 Journal of neuroimmune pharmacology Method HIV R105E 21 26 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The previously discussed M20A which appears to be specific for MHCI downregulation needs to be carefully investigated. 2011 Journal of neuroimmune pharmacology Method HIV M20A 25 29 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The standard designations for these mutations are M20A, AAAA and AXXA, R106A and EDAA, and LLAA. 2011 Journal of neuroimmune pharmacology Method HIV M20A;R106A 50;71 54;76 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. These remarkable findings in which D123E (BLOSUM62 score, +2) has the exact same phenotype as mutations with BLOSUM62 scores ranging from -1 to -4, implies a unique role for D123 in Nef function. 2011 Journal of neuroimmune pharmacology Method HIV D123E 35 40 Nef 182 185 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. This last Nef phenotype is also lost with the E160A mutation. 2011 Journal of neuroimmune pharmacology Method HIV E160A 46 51 Nef 10 13 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Thus, three obvious mutations for Nef to test for a SH3 domain protein requirement in a given Nef function are the single mutations, P72A, P75A, and R77A. 2011 Journal of neuroimmune pharmacology Method HIV P72A;P75A;R77A 133;139;149 137;143;153 Nef;Nef 34;94 37;97 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Unlike the other signature mutations discussed above, it is known that a single conservative mutation D175E gives the same fully defective phenotype as the double alanine mutation. 2011 Journal of neuroimmune pharmacology Method HIV D175E 102 107 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The ~4-fold resistance of CC101.6 compared to its parent virus stems largely from an H308P polymorphism in the V3 region that presumably allows for improved exploitation of lower levels of free CCR5. 2011 Virology Method HIV H308P 85 90 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. 10 mul PR L76V at a final concentration of 34 nM from active site titration with SQV was mixed with 100 mul of reaction buffer [100 mM MES (4-morpholineethanesulfonic acid), pH 5.6, 400 mM NaCl, 1 mM ethylenediaminetetraacetic acid, and 5% glycerol] at 26 C. 2011 Biochemistry Method HIV L76V 10 14 PR 7 9 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. A second construct, containing two mutations, M46I and L76V, in the PR domain of TFR-PR was also made using TFR-PRL76V as the template. 2011 Biochemistry Method HIV L76V;L76V;M46I 55;114;46 59;118;50 PR;PR;PR 68;85;112 70;87;114 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The HIV-1 PR (Genbank HIVHXB2CG) clone optimized for structural and biochemical studies contains mutations Q7K, L33I and L63I to minimize autoproteolysis, and C67A and C95A to prevent cysteine-thiol oxidation. 2011 Biochemistry Method HIV C67A;C95A;L33I;L63I;Q7K 159;168;112;121;107 163;172;116;125;110 PR 10 12 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The L76V mutation was introduced in this PR template as well as the template encoding a PR precursor mimetic in which the full-length transframe region (TFR) is fused to the N-terminus of PR (TFR-PR) by use of the appropriate oligonucleotide primers using the QuikChange protocol (Stratagene, La Jolla, CA) and verified by DNA sequencing. 2011 Biochemistry Method HIV L76V 4 8 Capsid;PR;PR;PR;PR 303;41;88;188;196 305;43;90;190;198 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The precursor was folded by addition of 5.66 volumes of 5 mM sodium acetate buffer, pH 5.3, with or without added DRV, to TFR-PRL76V in 12 mM HCl, to give a final pH of 4.5. 2011 Biochemistry Method HIV L76V 128 132 PR 126 128 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Thus, remnants of the unprocessed precursor TFR-PRL76V and TFR-PRM46I/L76V were purified as described. 2011 Biochemistry Method HIV L76V 70 74 PR;PR 48;63 50;65 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. 18 microM rhesus or human TRIM5alpha CC-SPRY proteins were added to a solution of isolated HIV-1 A14C/E45C or P207C/T216C cores (~11 microg/ml). 2011 PLoS pathogens Method HIV E45C;P207C;T216C;A14C 102;110;116;97 106;115;121;101 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Briefly, 30 microl P207C/T216C or A14C/E45C CA were preassembled in the presence of 50 microM DTT under the conditions described above. 2011 PLoS pathogens Method HIV A14C;E45C;P207C;T216C 34;39;19;25 38;43;24;30 Capsid 44 46 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. HIV-1 viruses were produced by transient transfection of sixty dishes of 6x106 293T cells with 10 microg plasmid DNA (using 10 microg of HIV-1 construct R9, R9.Env-, or R9.A14C/E45C) using polyethylenimine (3.6 microg/ml, Polysciences) in each 10 cm dish. 2011 PLoS pathogens Method HIV E45C;A14C 177;172 181;176 Env 160 163 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Quantification of A14C/E45C and P207C/T216C cores in the presence of human and rhesus TRIM5alpha CC-SPRY. 2011 PLoS pathogens Method HIV A14C;E45C;P207C;T216C 18;23;32;38 22;27;37;43 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. Samples collected at 14 weeks, 6 months, and 12 months of age were analyzed using the LigAmp assay to detect the K103N mutation (assay cutoff: 0.5% K103N) and the Y181C mutation (assay cut-off: 1% Y181C). 2011 AIDS (London, England) Method HIV K103N;K103N;Y181C;Y181C 113;148;163;197 118;153;168;202 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. For cloning the Gag-Y164A and Env-R515A mutants into a lentiviral vector, we first amplified the Y164A Gag region from our NL4-3 based vectors and used TOPO cloning to insert the Gag region into the ViraPower Lentiviral expression systems (Invitrogen) to generate pLenti-Y164A. 2011 Virology Method HIV R515A;Y164A;Y164A;Y164A 34;20;97;271 39;25;102;276 Env;Gag;Gag;Gag 30;16;103;179 33;19;106;182 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Subsequently the Env region from R515A Env vector was cut with EcoR1 Xho1 and subcloned downstream of the Gag region to generate pLenti-Y164A/R515A. 2011 Virology Method HIV R515A;R515A;Y164A 33;142;136 38;147;141 Env;Env;Gag 17;39;106 20;42;109 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Y795S/LL799HQ/Y802SFP - 5'GGAAGCCCTCAAACTTGGTGGAATCACCAACAGTCTTGGAGTCAGG3'. 2011 Retrovirology Method HIV Y795S 0 5 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Y795S/LL799HQ/Y802SRP - 5'CCTGACTCCAAGACTGTTGGTGATTCCACCAAGATTTGAGGGCTTCC3'. 2011 Retrovirology Method HIV Y795S 0 5 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The study was powered to detect a difference in the D30N groups (D30N and D30N + M184V) versus control (wild-type). 2010 The open medical informatics journal Method HIV D30N;D30N;D30N;M184V 52;65;74;81 56;70;78;86 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Thy/liv implants (n=5 mice per group) were infected by direct injection of 100 infectious units of either wild type HIV-1NL4-3 or HIV-1 NL4-3 containing the D30N, the M184V, or both the D30N and M184V mutations or were mock infected with medium alone. 2010 The open medical informatics journal Method HIV D30N;D30N;M184V;M184V 157;186;167;195 161;190;172;200 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Viral mutants were generated by the introduction of the D30N and M184V mutations into a molecularly cloned strain of HIV (HIV-1NL4-3) by site-directed mutagenesis. 2010 The open medical informatics journal Method HIV D30N;M184V 56;65 60;70 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. AS-PCR for K103N and Y181C. 2011 AIDS (London, England) Method HIV K103N;Y181C 11;21 16;26 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. PCR products were further tested for the K103N mutation using an allele-specific-PCR assay, as previously described. 2011 AIDS (London, England) Method HIV K103N 41 46 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. Additionally, the baseline sample from delivery (supposed to contain HIV-1 wild type only) had to be amplifiable in order to establish an individual cut-off in the ASPCR for detection of NVP-resistant virus; quantification of drug-resistant HIV-1 variants carrying the K103N and/or the Y181C mutation in the pol gene were done by ASPCR assays as previously described. 2011 PloS one Method HIV K103N;Y181C 269;286 274;291 Pol 308 311 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. For this purpose, the maximum proportion of K103N or Y181C ever observed during the observation period of an individual was used as the presence of both mutations on the same genome cannot be excluded; this approach underestimates the total proportion of NVP-resistant virus in case the 2 mutations are located on different HIV-1 genomes. 2011 PloS one Method HIV K103N;Y181C 44;53 49;58 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. The detection limits for the 3 mutations as estimated from plasmid DNA controls were 0.019% K103N (AAC), 0.013% K103N (AAT) and 0.29% Y181C (TGT) in the presence of wild-type HIV-1. 2011 PloS one Method HIV K103N;K103N;Y181C 92;112;134 97;117;139 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. The proportions of K103N (codon AAC) and K103N (codon AAT) mutants were summed to obtain the total proportion of virus harboring the K103N mutation. 2011 PloS one Method HIV K103N;K103N;K103N 19;41;133 24;46;138 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. For subtypes B and C, the Subtype B-1MM-2 primer and Subtype C-1MM-2 primers, respectively, were used to give rise to K65R-containing transcripts. 2011 PloS one Method HIV K65R 118 122 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. It is important to note that the terminal "A" of the Subtype C-1MM-2A primer was not underlined because it is responsible for the production of wild-type, K65K-containing products as opposed to products with mutagenic nt insertions. 2011 PloS one Method HIV K65K 155 159 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Nt in parentheses represent potential sites of K65R development and dislocation. 2011 PloS one Method HIV K65R 47 51 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Primer-dependent and independent K65R production and template dislocation experiments. 2011 PloS one Method HIV K65R 33 37 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Primer-independent and dependent generation of K65R, K65T and K65I and template dislocation. 2011 PloS one Method HIV K65I;K65R;K65T 62;47;53 66;51;57 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. These reactions were carried out under conditions similar to those described above with the exception of the addition of 10 microM of dGTP only (Invitrogen, Carlsbad, CA, USA) as opposed to all four nt in the primer-dependent K65R generation assays. 2011 PloS one Method HIV K65R 226 230 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. To ensure that the dislocation reaction was specific to the generation of the K65R mutation, primers were used that contained each of the three other possible nt at the mutagenic position at the 3' end, such that mismatching with the template sequence would occur to yield K65K, K65T or K65I-containing transcripts in a primer-dependent manner. 2011 PloS one Method HIV K65I;K65K;K65R;K65T 287;273;78;279 291;277;82;283 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. To evaluate whether the erroneous incorporation of the other nt alternatives would influence dGTP incorporation and K65R production, we also performed the primer-independent DNA synthesis experiments in the presence of dCTP and dTTP, to yield K65T- and K65I-containing transcripts, respectively. 2011 PloS one Method HIV K65I;K65R;K65T 253;116;243 257;120;247 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. To study the generation of K65R in a primer-dependent manner, the primers used contained a mutagenic G at their 3' end in order to yield K65R-containing transcripts. 2011 PloS one Method HIV K65R;K65R 27;137 31;141 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. To study the template-derived generation of K65R in a primer-independent manner, we used primers that did not contain mutagenic nt but instead used only dGTP to exclusively yield transcripts containing the mutagenic nt. 2011 PloS one Method HIV K65R 44 48 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. A plot of the measured values versus the input was linear across a wide range of K103N mutants frequencies. 2011 PloS one Method HIV K103N 81 86 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. At least 2500 reads reliably detects minor K103N mutants when they accounted for over 1.5% of the quasispecies. 2011 PloS one Method HIV K103N 43 48 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Our assay detects K103N mutants down to a frequency of 0.01%. 2011 PloS one Method HIV K103N 18 23 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Reciprocal validation of allele-specific PCR and ultra-deep pyrosequencing was also performed by quantifying in parallel mixtures of wild-type and K103N mutants with known proportions of K103N by the two methods. 2011 PloS one Method HIV K103N;K103N 147;187 152;192 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The sensitivity of our allele-specific PCR assay to detect K103N mutants was assessed on mixtures of wild-type and K103N mutants. 2011 PloS one Method HIV K103N;K103N 59;115 64;120 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. Anti-HIV replication assay against NL4-3 (K101E) and RTMDR strains in TZM-bl cell lines. 2011 European journal of medicinal chemistry Method HIV K101E 42 47 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. NL4-3 (K101E) or RTMDR at a multiplicity of infection (MOI) of 0.001 was used to infect TZM-bl cells. 2011 European journal of medicinal chemistry Method HIV K101E 7 12 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. HIV-1 quantification, resistance testing, and AS-PCR for detection and quantification of minority drug-resistant HIV-1 variants harboring K103N and/or M184V mutations were performed as described previously. 2011 PloS one Method HIV K103N;M184V 138;151 143;156 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Experimental biases due to the recombination event with two different amplicons were excluded by verifying that HR1-HR2 and full Env recombinant viruses produced from HXB2 and from an otherwise identical HXB2-derived double mutant carrying the G36S+V38M mutations in gp41 (HXB2-SIM) featured similar IC50 and infectivity levels (data not shown). 2011 PloS one Method HIV G36S;V38M 244;249 248;253 gp41;Env 267;129 271;132 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. An OLA was performed on all amplicons derived from plasma and PBMC using probes that detect mutations associated with high-level drug-resistance to NFV, codons D30N (AAT) and L90M (ATG), nucleoside reverse transcriptase inhibitors (NRTI) at codons K70R (AGA), M184V (GTG), and T215F/Y (TTC, TAC), and non-nucleoside reverse transcriptase inhibitors (NNRTI) at codons K103N (AAC), Y181C (TGT), and G190A (GCA) as described. 2011 Journal of acquired immune deficiency syndromes (1999) Method HIV D30N;G190A;K103N;K70R;L90M;M184V;T215F;T215Y;Y181C 160;397;367;248;175;260;277;277;380 164;402;372;252;179;265;284;284;385 NNRTI;NRTI;NNRTI;NRTI 301;187;350;232 337;219;355;236 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. The following isolates were used as control reference viruses in each experiment: HXB2, xxBRUpitt, and HIV-1SUM 9 as WT viruses; M184Vpitt as 3TC-resistant virus carrying the M184V mutation. 2011 PloS one Method HIV M184V 175 180 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. X403-4 and X82-5 are NVP-resistant isolates carrying the Y181C or K103N/Y181C mutations, respectively. 2011 PloS one Method HIV K103N;Y181C;Y181C 66;57;72 71;62;77 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. Analogous assays were performed using a variant HIV strain that encodes the Tyr181Cys (Y181C) mutation of HIV-RT. 2011 Journal of the American Chemical Society Method HIV Y181C;Y181C 76;87 85;92 RT 110 112 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Single (E92Q, T97A, G140S, Q148R, Y143C, N155H) and double (G140S/Q148R, Y143C/N155H, E92Q/Y143C and T97A/Y143C) mutations were introduced into the HIV-2 wild-type N1 sequence by mutagenesis using the QuickChange II site-directed mutagenesis kit (Agilent Technologies, Santa Clara, USA) according to the manufacturer instructions. 2011 Retrovirology Method HIV E92Q;E92Q;G140S;G140S;N155H;N155H;Q148R;Q148R;T97A;T97A;Y143C;Y143C;Y143C;Y143C 8;86;20;60;41;79;27;66;14;101;34;73;91;106 12;90;25;65;46;84;32;71;18;105;39;78;96;111 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. Expression and purification of RAV-1 IN CCD and RAV-1 IN CCD mutants (A182T, H103A, H103A/182T) 2011 PloS one Method HIV A182T;H103A;H103A 70;77;84 75;82;89 IN;IN 37;54 39;56 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. Expression and purification of RAV-1 IN CCD and RAV-1 IN CCD mutants (A182T, H103A, H103A/182T). 2011 PloS one Method HIV A182T;H103A;H103A 70;77;84 75;82;89 IN;IN 37;54 39;56 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. pETG10a-INRAV1CCD, pETG10a-INRAV1CCDA182T, pETG10a-INRAV1CCDH103A and pETG10a-INRAV1CCDH103A/A182T were introduced into E. 2011 PloS one Method HIV A182T;A182T;H103A;H103A 93;36;60;87 98;41;65;92 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. pETG10a-INRAV1CCDH103C was introduced in E. 2011 PloS one Method HIV H103C 17 22 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. The pETG10a-INRAV1CCDA182T, pETG10a-INRAV1CCDH103A, pETG10a-INRAV1CCDH103A/A182T, pETG10a-INRAV1CCDH103C and pET30a-INRAV1-H130C sequences were created by site-directed mutagenesis (Stratagene QuickChange kit) using pETG10a-INRAV1CCD and pET30a-INRAV1 as a template for the following mutagenic primers (mutations are shown as lowercase letters): 5'-GTTCCCCCTGTTTGCTggtGGGGATTCTTTTCATAAAG-3' (F-A182T), 5'-CTTTATGAAAAGAATCCCCaccAGCAAACAGGGGGAAC-3' (R-A182T); 5'-GCCGTGGCCCAATGagcTTGTGCAGCAACCG-3' (F-H103A), 5'-CGGTTGCTGCACAAgctCATTGGGCCACGGC-3' (R-H103A) and 5'- GCCGTGGCCCAATGacaTTGTGCAGCAACCG-3' (F-H103C), 5'- CGGTTGCTGCACAAtgtCATTGGGCCACGGC-3' (R-H103C). 2011 PloS one Method HIV A182T;A182T;A182T;H103A;H103A;H103C;H103C;H130C 75;394;450;499;548;601;651;123 80;399;455;504;553;606;656;128 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Next, we introduced the N348I/A/Q/E/R/L mutations into the p51 subunit of HIV-1 RT, and carried out energy minimizations as described above. 2011 Retrovirology Method HIV N348A;N348E;N348I;N348L;N348Q;N348R 24;24;24;24;24;24 39;39;39;39;39;39 RT 80 82 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. The N348A, N348E, N348L, N348Q and N348R mutations were introduced into the wild-type (WT) p6HRT-Prot prokaryotic expression vector by site-directed mutagenesis using the QuikChange mutagenesis kit (Stratagene La Jolla, CA). 2011 Retrovirology Method HIV N348A;N348E;N348L;N348Q;N348R 4;11;18;25;35 9;16;23;30;40 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In viruses HXB2, PR-1 and PR-2, Gag substitutions V362I, A364V, S368N and V370A were introduced by site-directed mutagenesis. 2011 Retrovirology Method HIV A364V;S368N;V362I;V370A 57;64;50;74 62;69;55;79 Gag;PR;PR 32;17;26 35;19;28 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. A silent mutation was introduced into the human Tnp3 cDNA to make it resistant to shRNA targeting by QuickChange II XL (Stratagene) following the manufacturer's instruction with primers C498A forward CGAATTGGAGCTAATCGGCGAACAGAAATTATAGAAGATTTG and C498A reverse CAAATCTTCTATAATTTCTGTTCGCCGATTAGCTCCAATTCG. 2011 PLoS pathogens Method HIV C498A;C498A 186;247 191;252 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Plasmids encoding RT in which one or two amino acid residues were substituted (L100I, K103N, V106A, Y181C, Y188L, G190A and K103N/Y181C) were constructed by amplifying the gene in two fragments using the oligonucleotides listed in Table S1. 2011 Bioorganic & medicinal chemistry Method HIV G190A;K103N;K103N;L100I;V106A;Y181C;Y181C;Y188L 114;86;124;79;93;100;130;107 119;91;129;84;98;105;135;112 RT 18 20 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. RT genes containing mutations K103N and G190A were inserted into a pBRP-HR vector, other mutant genes were subcloned into pET-21d-2c. 2011 Bioorganic & medicinal chemistry Method HIV G190A;K103N 40;30 45;35 RT 0 2 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. Drug resistant XMRV RT mutants Q190M and K103R (equivalent to HIV-1 Q151M RT and K65R) were generated by site-directed mutagenesis using forward and reverse primers 2 and 3. 2012 Nucleic acids research Method HIV K65R;K103R;Q190M 81;41;31 85;46;36 RT;RT 20;74 22;76 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. # U08453), and a derivative of AN1 (subtype B, sequence available at http://ubik.mullins.microbiol.washington.edu/HIV/Doria-Rose2005/) harboring a N201Q substitution that enhances binding to alpha4beta7. 2011 PloS one Method HIV N201Q 147 152 21932031 1H, 15N, and 13C resonance assignments for a monomeric mutant of the HIV-1 capsid protein. For 15N/13C labeling of HIV1CA, bacteria were grown in medium P040, with 25 mM 15N NH4Cl and 0.4% 13C glucose and all the inorganic salts in P5052N. 2012 Biomolecular NMR assignments Method HIV P5052N 141 147 21932031 1H, 15N, and 13C resonance assignments for a monomeric mutant of the HIV-1 capsid protein. Peter Prevelige, Jr) encoding W184A/M185A HIV-1 CA was used. 2012 Biomolecular NMR assignments Method HIV M185A;W184A 36;30 41;35 Capsid 48 50 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. At weeks 3 and 6, mice were boosted subcutaneously with wt gp120 or N448Q gp120 (5 mug per animal) along with adjuvant QS21 (20 mug per animal), provided by Agenus Inc., Lexington, MA in a total volume of 100 mul at two separate sites in the back of each mouse. 2011 Vaccine Method HIV N448Q 68 73 gp120;gp120;Matrix 59;74;181 64;79;183 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Recombinant gp120 proteins of HIV-1 BH10 (a molecular clone of LAI) with the wild-type sequence or with N448Q or N448E mutations were generated in transfected CHO-L761h cells as described previously. 2011 Vaccine Method HIV N448E;N448Q 113;104 118;109 gp120 12 17 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. For HIV-2 Y143C, Q148R, N155H and Q148R with N155H, mutations were introduced into a pol-spanning Hind III subclone of pROD9 (pBS-RODH3, HIV-2 nucleotides 1457-5787). 2011 AIDS (London, England) Method HIV N155H;N155H;Q148R;Q148R 24;45;17;34 29;50;22;39 Pol 85 88 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. The N155H HIV-1 replacement was initially constructed in an Apa I-Eco R1 subclone of pNL4-3 (pBS-pol, HIV-1 nucleotides 2010-5743). 2011 AIDS (London, England) Method HIV N155H 4 9 Pol 97 100 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. P147L, S149A poorly infectious, infectivity rescued by VSV-G, attenuated phenotype. 2011 Virology Method HIV S149A;P147L 7;0 12;5 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. WT and mutant (Y145A, P147L, S149A, and I150A) CA proteins were expressed in E. 2011 Virology Method HIV I150A;P147L;S149A;Y145A 40;22;29;15 45;27;34;20 Capsid 47 49 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Y145A, I150A, L151A noninfectious, severe defects in core morphology and stability. 2011 Virology Method HIV I150A;L151A;Y145A 7;14;0 12;19;5 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Wild-type and E45A HIV-1 particles were produced by transfecting 293T cells with three plasmids: pL-VSV-G (a kind gift from M. 2011 Structure (London, England Method HIV E45A 14 18 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. The double mutation G140S/Q148H was constructed by using the previously generated Q148H mutant and the appropriate oligonucleotides for the second mutation, G140S. 2012 Chemical biology & drug design Method HIV G140S;G140S;Q148H;Q148H 20;157;26;82 25;162;31;87 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. The following sense with cognate antisense (not shown) oligonucleotides (Integrated DNA Technologies, Coralville, IA) were used in the mutagenesis: Y143R, 5'-GCAGGAATTTGGCATTCCCCGCAATCCCCAAAGTCAAGGA-3'; N155H, 5'-CCAAAGTCAAGGAGTAATAGAATCTATGCATAAAGAATTAAAGAAAATTATAGGACA-3'; G140S, 5'-GGGGATCAAGCAGGAATTTAGCATTCCCTACAATC-3'; Q148H, 5'-CATTCCCTACAATCCCCAAAGTCATGGAGTAATAGAATCTA-3'. 2012 Chemical biology & drug design Method HIV G140S;N155H;Q148H;Y143R 275;203;325;148 280;208;330;153 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Using this construct as the wild-type template, the following HIV-1 integrase-resistant mutants were prepared via the QuikChange II XL (Stratagene, La Jolla, CA) site-directed mutagenesis protocol: Y143R, N155H, and G140S/Q148H. 2012 Chemical biology & drug design Method HIV G140S;N155H;Q148H;Y143R 216;205;222;198 221;210;227;203 IN;Capsid 68;158 77;160 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. RT mutations were identified from the International AIDS Society USA Drug (IAS-USA) mutation tables, spring 2008 (http://www.iasusa.org/resistance_mutations): M41L, K65R, D67N, insertion 69, K70R/E, L74I/V, L100I, K103N, V106A/M, V108I, Q151M, Y181I/C, M184V, Y188C/L, G190A/S, L210W, T215Y/F, K219Q/E, P225H and M230L. 2011 PloS one Method HIV D67N;G190A;G190S;K103N;K219E;K219Q;K65R;K70E;K70R;L100I;L210W;L74I;L74V;M184V;M230L;M41L;P225H;Q151M;T215F;T215Y;V106A;V106M;V108I;Y181C;Y181I;Y188C;Y188L 171;269;269;214;294;294;165;191;191;207;278;199;199;253;313;159;303;237;285;285;221;221;230;244;244;260;260 175;276;276;219;301;301;169;197;197;212;283;205;205;258;318;163;308;242;292;292;228;228;235;251;251;267;267 RT 0 2 AIDS 52 56 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. The only additions to this list since that time are K101H, E138A, and M230L, all etravirine-associated changes and K101P associated with resistance to NVP, EFV and etravirine. 2011 PloS one Method HIV E138A;K101H;K101P;M230L 59;52;115;70 64;57;120;75 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Construction, expression and purification of JR-FL gp120wt and Q105N. 2012 Vaccine Method HIV Q105N 63 68 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. For the analysis of sera from the head-to-head comparison between gp120wt and Q105N, sera were serially diluted (starting at 1:50) and incubated on plates for 1 h. 2012 Vaccine Method HIV Q105N 78 83 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Mutant Q105N was generated by QuikChange mutagenesis (Agilent Technologies) using mutant DeltaN2mCHO as template. 2012 Vaccine Method HIV Q105N 7 12 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. The sequence of the Q105N mutant was verified by DNA sequencing. 2012 Vaccine Method HIV Q105N 20 25 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. To assess the antigenic profile of Q105N, microtiter plates were coated with Q105N at 2 mug/ml (in PBS) and serially diluted mAbs (F105, b6, b12, b13, VRC01, VRC03, CD4-IgG2, B4e8 and 2G12) assessed for binding starting at 5 mug/ml. 2012 Vaccine Method HIV Q105N;Q105N 35;77 40;82 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. To facilitate recombinant protein purification, the sequences for JR-FL gp120wt and mutant Q105N were appended with a C-terminal 8-HIS tag by standard PCR. 2012 Vaccine Method HIV Q105N 91 96 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. 293FTs (Invitrogen) were transfected with A114S, A114C, A114V or WT pD3HIV-GFP and pVSV-G. 2012 Virology Method HIV A114C;A114S;A114V 49;42;56 54;47;61 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Briefly 100nM of a 5' end 32P-labeled 23-mer extend-T primer and 200nM of cold primer were annealed to a 38-mer RNA template and extended with 100nM WT or A114C RT in presence of 800muM dTTP for single round incorporation and rapidly quenched with EDTA at different time points using the Kintek RFQ3 machine. 2012 Virology Method HIV A114C 155 160 RT 161 163 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The construction of the A114S, A114C, and A114V mutants were carried out using a site directed mutagenesis kit (Stragene). 2012 Virology Method HIV A114C;A114S;A114V 31;24;42 36;29;47 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. To determine the concentration of active WT and A114C RT, single-turnover burst assays were performed as described before. 2012 Virology Method HIV A114C 48 53 RT 54 56 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Mutated recombinant IN Q168L, IN W131A, IN K188Q, IN Y194E, IN Y194F were obtained by site-directed mutagenesis of the pINSD.His plasmid. 2011 Retrovirology Method HIV K188Q;Q168L;W131A;Y194E;Y194F 43;23;33;53;63 48;28;38;58;68 IN;IN;IN;IN;IN 20;30;40;50;60 22;32;42;52;62 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. The synthesis, purification and molecular characterization of synthetic Vpr1-96 (sVpr), the C-terminal peptides Vpr75-90 , Vpr69-78, Vpr75-84, Vpr81-90 and Vpr87-96 and the mutants Vpr75-90 (R76Q, V83I, T84I), Vpr75-90 (R76Q, V83I, R80A, T84I), Vpr75-90 (R80A) were performed as described in detail elsewhere and the purities were checked by HPLC, MALDI-MS and positive ion ESI-MS. 2011 BMC structural biology Method HIV R76Q;R76Q;R80A;R80A;T84I;T84I;V83I;V83I 191;220;232;255;203;238;197;226 195;224;236;259;207;242;201;230 Vpr;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr 72;112;123;133;143;156;181;210;245 75;115;126;136;146;159;184;213;248 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. 1T3R for the WT HIV-pr, 2F8G for the I50V mutant, and 3EM6 for the I50V/A71V double mutant HIV-pr. 2012 The journal of physical chemistry. B Method HIV A71V;I50V;I50V 74;39;69 78;43;73 PR;PR 21;97 23;99 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Biochemical analyses of recombinant HIV-1 RT containing A360V. 2012 PloS one Method HIV A360V 56 61 RT 42 44 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. HIV-1 RTs containing the A360V, TAM-1 or TAM-1/A360V mutations were purified to homogeneity as described previously. 2012 PloS one Method HIV A360V;A360V 47;25 52;30 RT 6 9 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Production of site-directed mutants containing A360V. 2012 PloS one Method HIV A360V 47 52 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The A360V mutation was also introduced by site-directed mutagenesis (QuickChange II Site-Directed Mutagenesis Kit; Agilent, La Jolla, CA) into the backbone of wildtype HIV-1 RT and into RTs that contained the D67N/K70R or M41L/L210W/T215Y (TAM-1) mutations in the p6HRT plasmid. 2012 PloS one Method HIV L210W;M41L;T215Y;A360V;D67N;K70R 228;223;234;4;210;215 233;227;239;9;214;219 Capsid;RT;RT 135;175;187 137;177;190 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Drug-resistant HIV-1 variants carrying the K103N (AAC) mutation and the K103N (AAT) mutation were summed to obtain the total proportion of virus carrying the K103N mutation. 2012 PloS one Method HIV K103N;K103N;K103N 43;72;158 48;77;163 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. In total, seven ASPCR assays were performed per sample: two AZT mutations confering high level resistance (T215Y, T215F) and one early AZT mutation (K70R) confering only low level resistance but indicating for emergence of AZT-resistance; additionally the two most common NVP-selected resistance mutations (K103N and Y181C) and the most frequent 3TC-selected mutation M184V were analysed (details in Materials and Methods S1). 2012 PloS one Method HIV K103N;K70R;M184V;T215F;T215Y;Y181C 307;149;368;114;107;317 313;153;373;119;112;322 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. The ubiquitin encoding plasmid, CMV2-Flag-UbK48R, was engineered by PCR amplification of K48R ubiquitin to include flanking NotI and EcoRI restriction sites and ligated into the N-terminal Flag expression vector pFlag-CMV-2 (Sigma, St. 2012 Virology Method HIV K48R 89 93 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Ubiquitin K48R was detected using anti-Flag mAb (Sigma). 2012 Virology Method HIV K48R 10 14 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. HIV-1 PR point mutants (I47V, L76V, V82A and N88D) were constructed using optimized HIV-1 PR template with Quikchange site-directed mutagenesis kit (Stratagene). 2012 Journal of medicinal chemistry Method HIV I47V;L76V;N88D;V82A 24;30;45;36 28;34;49;40 PR;PR 6;90 8;92 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. The HIV-1 PR (GenBank HIVHXB2CG) gene was cloned into pET11a expression vector (Novagen) and further optimized to restrict autoproteolysis (Q7K, L33I and L63I) and cysteine-thiol oxidation (C67A and C95A). 2012 Journal of medicinal chemistry Method HIV C67A;C95A;L33I;L63I;Q7K 190;199;145;154;140 195;203;149;158;143 PR 10 12 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The PR20/SQV crystal structure was solved by molecular replacement with the structure of PR mutant I50V in complex with DRV (2F8G) using MOLREP. 2012 Biochemistry Method HIV I50V 99 103 PR;PR 4;89 6;91 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. The following resistance mutations were scored: to nucleoside reverse transcriptase inhibitors (NRTIs): M41L, K65R, D67N/G/E, T69D/insertion, K70R/E, L74V/I, V75M/T/A/S, F77L, Y115F, F116Y, Q151M, M184V/I, L210W, T215Y/F/I/S/C/D/V/E, K219Q/EN/R; to non-nucleoside reverse transcriptase inhibitors (NNRTIs): L100I, K101E/P, K103N/S, V106A/M, V179F, Y181C/I/V, Y188C/L/H, G190A/S/E, P225H, M230L; and to protease inhibitors (PIs): L23I, L24I, D30N, V32I, M46I/L, G48V/M, I50L/V, F53L/Y, I54V/L/M/A/T/S, G73S/T/C/A, L76V, V82A/T/F/S/C/M/L, N83D, I84V/A/C, N88D/S, L90M. 2012 PloS one Method HIV D30N;D67E;D67G;D67N;F116Y;F53L;F53Y;F77L;G190A;G190E;G190S;G48M;G48V;G73A;G73C;G73S;G73T;I50L;I50V;I54A;I54L;I54M;I54S;I54T;I54V;I84A;I84C;I84V;K101E;K101P;K103N;K103S;K219E;K219N;K219Q;K219R;K65R;K70E;K70R;L100I;L210W;L23I;L24I;L74I;L74V;L76V;L90M;M184I;M184V;M230L;M41L;M46I;M46L;N83D;N88D;N88S;P225H;Q151M;T215C;T215D;T215E;T215F;T215I;T215S;T215V;T215Y;T69D;V106A;V106M;V179F;V32I;V75A;V75M;V75S;V75T;V82A;V82C;V82F;V82L;V82M;V82S;V82T;Y115F;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 441;116;116;116;183;477;477;170;370;370;370;461;461;501;501;501;501;469;469;485;485;485;485;485;485;543;543;543;314;314;323;323;234;234;234;234;110;142;142;307;206;429;435;150;150;513;561;197;197;388;104;453;453;537;553;553;381;190;213;213;213;213;213;213;213;213;126;332;332;341;447;158;158;158;158;519;519;519;519;519;519;519;176;348;348;348;359;359;359 445;124;124;124;188;483;483;174;379;379;379;467;467;511;511;511;511;475;475;499;499;499;499;499;499;551;551;551;321;321;330;330;244;244;244;244;114;148;148;312;211;433;439;156;156;517;565;204;204;393;108;459;459;541;559;559;386;195;232;232;232;232;232;232;232;232;130;339;339;346;451;168;168;168;168;535;535;535;535;535;535;535;181;357;357;357;368;368;368 NNRTI;NRTI;PR;NNRTI;NRTI;PI 249;51;402;298;96;423 285;83;410;304;101;426 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Complete assignments of the 2D 1H-15 N HSQC spectra for the E45A, R132T and E45A/R132T mutant proteins were obtained unambiguously by direct comparison with the spectrum of wild-type protein since the spectra of the mutants are essentially identical to that of wild-type, except for few resonances arising from amino acids around the mutation sites. 2012 Retrovirology Method HIV E45A;E45A;R132T;R132T 60;76;66;81 64;80;71;86 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Following identification of additional mutations by DNA sequencing of the PCR products, the corresponding SpeI-ApaI fragments were transferred into R9.E45A or R9.P38A proviral clones. 2012 Retrovirology Method HIV E45A;P38A 151;162 155;166 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Most of the E45A protein was present in the flow-through. 2012 Retrovirology Method HIV E45A 12 16 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. R9 clones encoding mutations E45A and P38A in CA were previously described and were the generous gift of Dr. 2012 Retrovirology Method HIV E45A;P38A 29;38 33;42 Capsid 46 48 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The assignment of the P38A mutant spectra were less straightforward since more (~ 20) resonances exhibited changes > 0.1 ppm from the wild type. 2012 Retrovirology Method HIV P38A 22 26 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The individual single R132T and T216I mutants were constructed by transferring the mutant SpeI-ApaI segments into the wild-type R9 plasmid. 2012 Retrovirology Method HIV R132T;T216I 22;32 27;37 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. F519I specifies a preferred use of the unoccupied, high-VCV affinity form of CCR5. 2012 Virology Method HIV F519I 0 5 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. G516V allows both double FP mutants to use VCV-CCR5 complexes for entry. 2012 Virology Method HIV G516V 0 5 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. T244A appears to counter the VCV-resistance phenotype created by the FP changes. 2012 Virology Method HIV T244A 0 5 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The clonal viruses listed in Table 1 were designed to investigate individually and in pair-wise combinations the effects of three FP changes (G516V, M518V, F519I) on the VCV-resistant phenotype of the D1/85.16 lineage. 2012 Virology Method HIV F519I;G516V;M518V 156;142;149 161;147;154 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The G516V change is critical to VCV resistance in PBMC and TZM-bl cells. 2012 Virology Method HIV G516V 4 9 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. To have a substantial impact, G516V must be accompanied by either M518V or F519I. 2012 Virology Method HIV F519I;G516V;M518V 75;30;66 80;35;71 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Different mutation profiles were created including K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, K101Q, V179D/Y181C/H221Y, V179D/Y181C, V179D/H221Y, V179D, K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y, and K103N. 2012 AIDS research and treatment Method HIV H221Y;H221Y;H221Y;K101Q;K103N;V179D;Y181C;Y181C;Y181C;H221Y;H221Y;H221Y;K101Q;K101Q;K101Q;K103N;K103N;K103N;V179D;V179D;V179D;Y181C;Y181C;Y181C 63;115;167;51;155;103;57;109;161;89;141;193;70;83;96;174;187;204;122;135;148;76;128;180 68;120;172;56;160;108;62;114;166;94;146;198;75;88;101;179;192;209;127;140;153;81;133;185 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Genotype-resistant results of these patients showed all samples contained three NNRTIs mutations (Y181C/H221Y plus another mutation) which conferred resistance to NVP. 2012 AIDS research and treatment Method HIV H221Y;Y181C 104;98 109;103 NNRTI 80 86 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Ltd.) with mutagenic primers: 221Y H, 5'-ACAAAAAACATCAGAAA GAACCTCCAT-3' (H221-F (C-6/P-110)), 5'-ACAAAAAACATCAGAAAGAACCCCC-3' (H221-F(P-22)), 5'-CTGGTGTGGTAAATCCCCACCT-3' (H221-R(C-6-2)), 5'-CTGGTGTGTAAAACCCCCACCTTAAC-3' (H221-R (P-22)), and 5'-CTGGTGT GTAAAATCCCCACCTCAA-3' (H221-R(P-110)); 181C Y, 5'-ATAGTTATC TATC AATACATGGATGATTTGTATGT-3' (Y181-F(C-6/P-110)829), 5'-ATGGAAATCT ATCAATACATGGATGATTTGT-3' (Y181-F(P-22-6)829), 5'-GTCTGGATTTTGTTTTCTAAAAGGCTC-3' (Y181-R 828). 2012 AIDS research and treatment Method HIV Y181F;Y181F;Y181R 346;409;464 353;416;471 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Several clones from each transformation were sequenced, and 3 clones containing 3 different NNRTIs mutation profiles, including K101Q/Y181C/H221Y, V179D/Y181C/H221Y, and K103N/Y181C/H221Y, were selected. 2012 AIDS research and treatment Method HIV H221Y;H221Y;H221Y;K101Q;K103N;V179D;Y181C;Y181C;Y181C 140;159;182;128;170;147;134;153;176 145;164;187;133;175;152;139;158;181 NNRTI 92 98 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. In all epidemiological models, SP use in pregnancy was considered the primary exposure of interest and the (1) dhfr (N51I/C59R/S108N), (2) dhps (A437G/K540E), or (3) combined dhfr/dhps genotypes as three separate outcomes. 2012 Malaria journal Method HIV C59R;N51I;S108N;A437G;K540E 122;117;127;145;151 126;121;132;150;156 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. ARV resistance was defined by mutations at the following positions: M41L, A62V, K65R, D67N, T69ins, K70R, L74VI, Y115F, F116Y, Q151M, M184VI, T210W, T215YF and K219QE for Nucleoside Reverse Transcriptase Inhibitors (NRTI), L100I, K101EP, K103NS, V106AM, Y181CIV, Y188CLH, G190ASC, and M230L for Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI), and D30N, V32I, M46IL, I47VA, G48VM, I50LV, I54VTALM, L76V, V82AFTS, I84V, N88S, and L90M for Protease Inhibitors (PI)."Any resistance" was defined by the presence of any of the mutations cited above. 2012 Journal of acquired immune deficiency syndromes (1999) Method HIV A62V;D30N;D67N;F116Y;G190A;G190C;G190S;G48M;G48V;I47A;I47V;I50L;I50V;I54A;I54L;I54M;I54T;I54V;I84V;K101E;K101P;K103N;K103S;K219E;K219Q;K65R;K70R;L100I;L74I;L74V;L76V;L90M;M184I;M184V;M230L;M41L;M46I;M46L;N88S;Q151M;T210W;T215F;T215Y;T69ins;V106A;V106M;V32I;V82A;V82F;V82S;V82T;Y115F;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 74;356;86;120;272;272;272;382;382;375;375;389;389;396;396;396;396;396;421;230;230;238;238;160;160;80;100;223;106;106;406;437;134;134;285;68;368;368;427;127;142;149;149;92;246;246;362;412;412;412;412;113;254;254;254;263;263;263 78;360;90;125;279;279;279;387;387;380;380;394;394;404;404;404;404;404;425;236;236;244;244;166;166;84;104;228;111;111;410;441;140;140;290;72;373;373;431;132;147;155;155;98;252;252;366;419;419;419;419;118;261;261;261;270;270;270 NNRTI;NRTI;PR;NNRTI;NRTI;PI 295;171;446;344;216;467 331;203;454;349;220;469 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. As a control, we used two subtype C MJ4 plasmids, one wild type and one bearing K65R (both provided by Mark Wainberg's group in Montreal). 2012 PloS one Method HIV K65R 80 84 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Positions studied were codon 65 and codon 70, which was chosen as a TAM position in NRTI-treated patients leading to K70R, because it has been frequently observed in the studied isolates and because 70R is considered to be a DRM and not at all a substitution potentially related to polymorphism. 2012 PloS one Method HIV K70R 117 121 NRTI 84 88 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Univariate and multivariate logistic regression were used to identify variables associated with the presence of K65R. 2012 AIDS (London, England) Method HIV K65R 112 116 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. For comparison of peptide pools one-way ANOVA with Bonferroni's multiple comparison test was employed to assess differences between responses to W61D, IIIB and SF33. 2012 Retrovirology Method HIV W61D 145 149 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Animals were inoculated intravenously or orally with virulent uncloned SIVmac251, the K65R-containing virus SIVmac385 (which is derived from SIVmac251), or RT-SHIV as described in their original studies. 2012 Retrovirology Method HIV K65R 86 90 RT 156 158 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Real-time PCR for sensitive detection of K65R viral mutants. 2012 Retrovirology Method HIV K65R 41 45 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. The real-time PCR methodology to quantitate K65R mutants of SIV and RT-SHIV has been described previously . 2012 Retrovirology Method HIV K65R 44 48 RT 68 70 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. F16W was made by changing nucleotides 1967-1968 (5'-tc-3') to 5'-gg-3'. 2013 Virus research Method HIV F16W 0 4 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The concentrations of all proteins, except for the W37A and F16A/W37A aromatic mutants, were determined using an extinction coefficient of 6050 M-1 cm-1 at 280 nm. 2013 Virus research Method HIV F16A;W37A;W37A 60;51;65 64;55;69 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The concentrations of W37A and F16A/W37A, which lack tryptophan residues, were determined by amino acid analysis. 2013 Virus research Method HIV F16A;W37A;W37A 31;22;36 35;26;40 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The F16A mutation was introduced by changing nucleotides 1965-1968 (5'-tttc-3') to 5'-cgca-3', which altered the codon at position 16 from Phe to Ala in NC and also introduced an Fsp I restriction site at position 1963 that was used for tracking the mutation. 2013 Virus research Method HIV F16A;F16A 4;131 8;149 NC 153 155 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The F16W/W37F and F16A/W37A mutations were generated by consecutive mutagenesis of the requisite plasmids. 2013 Virus research Method HIV F16A;F16W;W37A;W37F 18;4;23;9 22;8;27;13 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The W37A mutation was incorporated by changing nucleotides 2029-2030 (5'-tg-3') to 5'-gc-3' and the W37F mutation changed nucleotides 2030-2031 (5'-gg-3') to 5'-tt-3'. 2013 Virus research Method HIV W37A;W37F 4;100 8;104 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. All GRFT samples were measured in 40 mM sodium phosphate buffer (pH 6.9), except for the Triple mutant D30A/D70A/D112A which also include 50 mM NaCl. 2012 Molecular pharmaceutics Method HIV D112A;D30A;D70A 113;103;108 118;107;112 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. For the D30A/D70A/D112A triple mutation, in some preps a slight variation was used. 2012 Molecular pharmaceutics Method HIV D112A;D30A;D70A 18;8;13 23;12;17 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. Single site mutations of GRFT (D30A, D70A, D112A) were made using the Stratagene QuikChange Site-Directed Mutagenesis or using a standard thermocycling strategy. 2012 Molecular pharmaceutics Method HIV D112A;D30A;D70A 43;31;37 48;35;41 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. The triple mutation of GRFT (D30A/D70A/D112A) was made using a standard thermocycling strategy and all mutants were confirmed by DNA sequencing. 2012 Molecular pharmaceutics Method HIV D112A;D30A;D70A 39;29;34 44;33;38 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. To monitor possible mass action in the oligomerization behavior of GRFT, the data were measured in intensity mode both at 0.3 and 0.9 OD at 230 and 280 nm (0.3, 0.6, 0.9 at 230 nm for the Triple mutant D30A/D70A/D112A), giving access to a wide concentration range. 2012 Molecular pharmaceutics Method HIV D112A;D30A;D70A 212;202;207 217;206;211 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Independent variables assessed in both univariate and multivariate analyses were CD4 count, HIV RNA, first-line failure, subtype CRF02_AG, and presence of G335D, A371V or 'other CD' mutation. 2012 Journal of acquired immune deficiency syndromes (1999) Method HIV A371V;G335D 162;155 167;160 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. The CD mutations considered were E312Q, Y318F, G333D/E, G335C/D, N348I, A360I, A360V, V365I, A371V, A376S, and E399G. 2012 Journal of acquired immune deficiency syndromes (1999) Method HIV A360I;A360V;A371V;A376S;E312Q;E399G;G333D;G333E;G335C;G335D;N348I;V365I;Y318F 72;79;93;100;33;111;47;47;56;56;65;86;40 77;84;98;105;38;116;54;54;63;63;70;91;45 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Thymidine analogue mutations (TAMs) were defined as M41L, D67N, K70R, L210W, T215F/Y, K219E/Q. 2012 Journal of acquired immune deficiency syndromes (1999) Method HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 58;86;86;64;70;52;77;77 62;93;93;68;75;56;84;84 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. However, in the preincubation buffer, active RT and template-primers D38/25PGA or D38T/25PGA were present at concentrations of 7-20 nM and 60 nM, respectively. 2012 Retrovirology Method HIV D38T 82 86 RT 45 47 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Mutagenic primers 5 -GCTGAGACAACATCTGTGGAGGTGGGGACTTACC-3 and 5 -GGTAAGTCCCCACCTCCACAGATGTTGTCTCAGC-3 were used to introduce L210W in plasmid p66RTB(LY). 2012 Retrovirology Method HIV L210W 127 132 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Synthetic oligonucleotides 21P, 25PGA, 31Trna, D38, D38rna, D38T, D38Trna and ProLac110 were obtained from Life Technologies. 2012 Retrovirology Method HIV D38T;D38T 60;66 64;72 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The competition between tenofovir-DP and dATP was analyzed with template-primer D38T/25PGA. 2012 Retrovirology Method HIV D38T 80 84 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The mutation R284K was added with primers 5 -GTAAACTCCTTAAAGGAACCAAAGCACTAAC-3 and 5 - GTTAGTGCTTTGGTTCCTTTAAGGAGTTTAC-3 . 2012 Retrovirology Method HIV R284K 13 18 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The plasmid p66RTB contains the nucleotide sequence encoding for the 66-kDa subunit of HIV-1BH10 RT, and p66RTB(LY) encodes a p66 derivative with thymidine analogue resistance mutations M41L and T215Y. 2012 Retrovirology Method HIV M41L;T215Y 186;195 190;200 RT 97 99 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Following cleavage of this intermediate construct with BsmB I, a double stranded DNA adapter, designed to restore the deleted sequence as well as to include a change in the triplet codon at position 66 (AAA) to either CGC (Lys66Arg), GCG (Lys66Ala), AAC (Lys66Asn) or ACC (Lys66Thr), was ligated into the BsmB I-digested plasmid. 2012 The FEBS journal Method HIV K66A;K66N;K66R;K66T 239;255;223;273 247;263;231;281 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. 0.8 to 400 nM or 3.1 to 400 nM 17b IgG was injected for a chip containing WT, E370A and M475A, and another chip containing WT, T257A and D474A gp120, respectively, in duplicate, to probe for the conformational effect of the mutations on gp120. 2013 Proteins Method HIV D474A;E370A;M475A;T257A 137;78;88;127 142;83;93;132 gp120;gp120 143;237 148;242 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. 17b was mixed with increasing concentrations of KR21 from 20 nM to 20 muM (T257A, D474A) or 2.5 nM to 40 muM (E370A, M475A) and injected over immobilized gp120 mutants for 5 min. 2013 Proteins Method HIV D474A;E370A;M475A;T257A 82;110;117;75 87;115;122;80 gp120 154 159 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. 8 mutants that showed some resistance to PT inhibition, 2 additional mutants based on criteria 3 (V255A) and 1 (V430A) and 1 mutant that showed no effect were further screened for KR21 direct binding and CD4 inhibition by an SPR on-chip capture method previously employed to study binding of IL5 mutants without pre-purification of proteins from expression supernatant. 2013 Proteins Method HIV V255A;V430A 98;112 103;117 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. All mutants were tested with KR21, except for N98A and N99A which had been previously tested with UM24 and were not re-tested in the current assay. 2013 Proteins Method HIV N98A;N99A 46;55 50;59 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. CD4 was injected over WT, K421A and E370A gp120 at different concentrations and 250 nM concentration was chosen for further competition studies with KR21 since this concentration resulted in more than 50 RUs of analyte bound to surface after association for all mutants and would yield high signals for competition measurements (not shown). 2013 Proteins Method HIV E370A;K421A 36;26 41;31 gp120 42 47 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Experiment was done in duplicate (triplicate for E370 and M475A) and average IC50s were reported. 2013 Proteins Method HIV M475A 58 63 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Peptide and CD4 were mixed such that concentration of CD4 was constant (35 nM) and that of KR21 varied from 6 nM to 100 muM (2.5 nM to 20 muM for E370A and M475A). 2013 Proteins Method HIV E370A;M475A 146;156 151;161 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Purified WT, T257A, D474A, E370A and M475A gp120 were immobilized on a Biacore CM5 chip using amide coupling following activation with EDC/NHS (Biacore manual, GE). 2013 Proteins Method HIV D474A;E370A;M475A;T257A 20;27;37;13 25;32;42;18 gp120 43 48 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The following forward primers and their reverse complements were used (in the 5'-3' direction): M95A: gagaacttcaacgcctggaagaacaac, K97A: aacttcaacatgtgggcgaacaacatggtggag, N98A: caacatgtggaaggccaacatggtggag, N99A: catgtggaagaacgccatggtggagcag, V101A: gtgggctaacaacatggcggagcagatgcacg, E102A: agaacaacatggtggcgcagatgcacgagga, K421A: ctgccctgccggatcgctcagatcatcaacatgtggc, V430A: catgtggcaggaggccggcaaggccatg, D474A: ggcccggcggcggcgccatgcgggacaactg R476A: ggcggcgacatggccgacaactggcgg, R480A: cgggacaactgggccagcgagctgtac (Invitrogen), T257A: cccgtggtgagcgcccagctgctgctg, E370A: ggcgaccccgccatcgtgacccac, I371A: ggcgaccccgaggccgtgacccacagc, V372A: gaccccgagatcgccacccacagcttc, M426A: cagatcatcaacgcctggcaggaggtg, M475A: ggcggcggcgacgcccgggacaactgg, V120A; ctgaagccctgcgccaagctgaccccc, K121A: gaagccctgcgtggccctgacccccctg, L122A: ccctgcgtgaaggccacccccctgtgc, V255A: catccggcccgtggcaagcacccagctg (IDTDNA). 2013 Proteins Method HIV D474A;E102A;E370A;I371A;K121A;K421A;K97A;L122A;M426A;M475A;M95A;N98A;N99A;R476A;R480A;T257A;V101A;V120A;V255A;V372A;V430A 408;285;568;601;781;325;131;818;673;709;96;172;208;447;483;532;244;745;854;637;371 413;290;573;606;786;330;135;823;678;714;100;176;212;452;488;537;249;750;859;642;376 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The T257A and D474A inhibition assays were done with 1 muM 17b Fab as we had used this analyte to be free of avidity effects in our direct binding assays, and it gave a robust binding signal (>50 RU) at 1 muM concentration for the mutants tested. 2013 Proteins Method HIV D474A;T257A 14;4 19;9 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. These mixtures were injected over the immobilized gp120 at 50 mul/min (5 mul/min for E370A and M475A) flow rate for 5 minutes. 2013 Proteins Method HIV E370A;M475A 85;95 90;100 gp120 50 55 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Thus 400 nM 17b IgG was used in the later assay with E370A and M475A in order to increase the signal from binding. 2013 Proteins Method HIV E370A;M475A 53;63 58;68 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The issue of whether 3TC precludes V184M reversal can be approached by means of a 2-by-2 table and Fisher's exact test. 2012 Viruses Method HIV V184M 35 40 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. There were no mutations but V184M reversal (and two other reversals) for the No drug regimen. 2012 Viruses Method HIV V184M 28 33 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Plasmids encoding amino changes Y143C, Q148R and N155H were generated as previously described. 2012 PloS one Method HIV N155H;Q148R;Y143C 49;39;32 54;44;37 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Out of the eight patients with DRMs, five of them developed at least one of the three major raltegravir resistance pathways (Y143R/C/H, Q148H/R/K and/or N155H/S), had longitudinal paired plasma and PBMC samples available, and had samples that could be successfully amplified and sequenced. 2012 PloS one Method HIV N155H;N155S;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 153;153;136;136;136;125;125;125 160;160;145;145;145;134;134;134 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Primary raltegravir-associated DRMs were defined to be E92Q, Y143R/C/H, Q148H/R/K, and N155H/S (HXB2 int amino acid coordinates), according to the International AIDS Society guidelines. 2012 PloS one Method HIV E92Q;N155H;N155S;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 55;87;87;72;72;72;61;61;61 59;94;94;81;81;81;70;70;70 AIDS 161 165 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Secondary raltegravir-associated DRMs were defined to be E92V, Q95K, T97A, F121Y, E138A/K, G140A/C/S, S147G, V151A/I/L, M154I/L, E157Q, and G163K/R, and linkages examined were T97A and Y143C/R, E138A/K and Q148H/K/R, G140S and Q148H/K/R, and G163K/R and N155H (consensus B definitions), according to Stanford University HIV-1 Drug Resistance Database. 2012 PloS one Method HIV E138A;E138A;E138K;E138K;E157Q;E92V;F121Y;G140A;G140C;G140S;G140S;G163K;G163K;G163R;G163R;M154I;M154L;N155H;Q148H;Q148H;Q148K;Q148K;Q148R;Q148R;Q95K;S147G;T97A;T97A;V151A;V151I;V151L;Y143C;Y143R 82;194;82;194;129;57;75;91;91;91;217;140;242;140;242;120;120;254;206;227;206;227;206;227;63;102;69;176;109;109;109;185;185 89;201;89;201;134;61;80;100;100;100;222;147;249;147;249;127;127;259;215;236;215;236;215;236;67;107;73;180;118;118;118;192;192 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Several differences could be observed between RTB' and RTC' (V35T, E36A, T39D, K43R, S48T, Q102K, D121Y, K122E, C162S, K173N, Q174K, D177E, T200A, Q207E, R211K); however, none of these differences were previously associated with NRTI resistance (Table 1). 2012 PloS one Method HIV C162S;D121Y;D177E;E36A;K122E;K173N;K43R;Q102K;Q174K;Q207E;R211K;S48T;T200A;T39D;V35T 112;98;133;67;105;119;79;91;126;147;154;85;140;73;61 117;103;138;71;110;124;83;96;131;152;159;89;145;77;65 NRTI 229 233 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Several differences in the RT gene sequence could be observed between these isolates (V35T, E36A, T39D, K43R, S48T, V90F, Q102R, D121Y, K122E, D123N, S134I, I135T, C162S, E169K, K173N, Q174K, D177E, T200A, Q207E, R211K, and F214L); none of them were previously related to NRTI resistance (Table 1). 2012 PloS one Method HIV C162S;D121Y;D123N;D177E;E169K;E36A;F214L;I135T;K122E;K173N;K43R;Q102R;Q174K;Q207E;R211K;S134I;S48T;T200A;T39D;V35T;V90F 164;129;143;192;171;92;224;157;136;178;104;122;185;206;213;150;110;199;98;86;116 169;134;148;197;176;96;229;162;141;183;108;127;190;211;218;155;114;204;102;90;120 NRTI;RT 272;27 276;29 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Vectors pHL[B-TAMs] and pHL[C-TAMs] were created by introducing NRTI resistance mutations D67N, K70R, T215Y/F, and K219Q into pHL[B-WT] and pHL[C-WT], respectively. 2013 Virology Method HIV D67N;K219Q;K70R;T215F;T215Y 90;115;96;102;102 94;120;100;109;109 NRTI 64 68 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Etravirine resistance was calculated using weighted scores, where L100I, K101P, Y181C/I/V result in the greatest impaired clinical response. 2013 AIDS (London, England) Method HIV K101P;L100I;Y181C;Y181I;Y181V 73;66;80;80;80 78;71;89;89;89 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Thymidine analog mutations (TAMs) included M41L, D67N, K70R, L210W, T215F/Y, K219E/Q) that were further designated as TAM 1 (M41-L210-T215Y) or TAM 2 (D67-K70-T215F-K219). 2013 AIDS (London, England) Method HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y;T215F;T215Y 49;77;77;55;61;43;68;68;159;134 53;84;84;59;66;47;75;75;164;139 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The gag amplicon was amplified by the primers A1-lower: 5' Acry-AGGGGTCGTTGCCAAAGAGTGA-3' (nt 2260-2281) and A1-upper: 5'-CACAGGAACAAGCAGCCAGGTC-3', and the amplicons were annealed with the sequencing primer C1548A: 5'-AAGGGGAAGTGATATAGCAGGATCTACTAGTA-3' (nt 1482-1513) to detect the T242N mutation or G1562A: 5'-TATAGCAGGATCTACTAGTACCCTTCAGGAACAA-3' (nt 1494-1527) to detect the V247I mutation. 2012 Retrovirology Method HIV C1548A;G1562A;T242N;V247I 208;302;284;380 214;308;289;385 Gag 4 7 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The tat/env fragment was amplified by using the PCR primers R-lower: 5' Acry-GGAAGCACCCAGGAAGTCAGC-3' (nt 5862-5882) and R-upper: 5'-GTATCCTCTGATGGGAGGGGCATA-3' (nt 7527-7550), and the amplicons were annealed with the sequencing primer Rev7: 5'-ATGCTACTTACTGCTTTGGTAGAGGCGCTTGATTA-3' (nt 6022-6056) to detect the I64T mutation or the sequencing primer Rev13: 5'-CCTCCTGAGGAATGGTTAAAGACTAT-3' (nt 7299-7324) to detect the R355K mutation. 2012 Retrovirology Method HIV I64T;R355K 313;421 317;426 Rev;Rev;Tat;Env 236;352;4;8 239;355;7;11 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The PDB entries are: 1T3R for the wild type (WT), 2F8G for the I50VPR, 2QD7 for the V82APR, and 2NNP for the I84VPR mutants. 2012 Journal of molecular graphics & modelling Method HIV I50V;I84V;V82A 63;109;84 69;115;90 23144597 Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation. As described above, Flap+ contains additional mutations of L10I, G48V, I54V, and V82A, and was expressed and purified similar to that of the WT. 2012 Journal of chemical theory and computation Method HIV G48V;I54V;L10I;V82A 65;71;59;81 69;75;63;85 23144597 Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation. For this experiment, protease that contains mutations at the primary auto-proteolysis site and at cysteine sites (Q7K, L33I, L63I, C67A and C95A) wasused, with the amino acid sequence: PQITL WKRPL VTIRI GGQLK EALLD TGADD TVIEE MNLPG KWKPK MIGGI GGFIK VRQYD QIIIE IAGHK AIGTV LVGPT PVNII GRNLL TQIGA TLNF. 2012 Journal of chemical theory and computation Method HIV C67A;C95A;L33I;L63I;Q7K 131;140;119;125;114 135;144;123;129;117 PR 21 29 23144597 Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation. The initial coordinates of the Flap+ variant were also from 1HHP and 2HB4, with the mutations (L10I, G48V, I54V, and V82A) modeled in using geometry in the AMBER package. 2012 Journal of chemical theory and computation Method HIV G48V;I54V;L10I;V82A 101;107;95;117 105;111;99;121 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Site-directed mutagenesis was then conducted with Phusion Site-directed Mutagenesis Kit(New England Biolabs) and the following mutations were introduced: D123E, V292I, K366R, T369A, T369V, A371V and I375V. 2012 PloS one Method HIV A371V;D123E;I375V;K366R;T369A;T369V;V292I 190;155;200;169;176;183;162 195;160;205;174;181;188;167 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Jurkat E6-1 cells were transduced at a MOI of 0.1 with retroviral vectors carrying the native HSP90AB1 gene and a catalytically inactive mutant of HSP90AB1E42A+D88A, as described previously. 2013 Virology Method HIV D88A 160 164 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Native HSP90AB1 and catalytically inactive mutant HSP90AB1E42A+D88A were cloned into a murine leukemia virus (MLV)-based retrovirus expression vector, as described earlier. 2013 Virology Method HIV D88A 63 67 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Overexpression of both native HSP90AB1 and the catalytically inactive mutant HSP90AB1E42A+D88A was compared on transduced Jurkat E6-1 cell lysates by immunoblotting. 2013 Virology Method HIV D88A 90 94 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. The I54V and V82A PR-mutant HIV clone has been described earlier. 2013 Virology Method HIV I54V;V82A 4;13 8;17 PR 18 20 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. The transduced Jurkat E6-1 cells were inoculated at a MOI of 0.05 with WT HIV and CA-mutant HIV, and the PR-mutant HIV PRI54V+V82A served as a positive control for rescue of reduced infectivity of the mutant viruses. 2013 Virology Method HIV V82A 126 130 Capsid;PR;PR 82;105;119 84;107;121 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. All protease genes, including wild type (WT), contained the polymorphism L63P. 2013 ACS chemical biology Method HIV L63P 73 77 PR 4 12 23252515 Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease. The synthetic gene for the wild-type (WT) HIV-1 protease sequence was made using codons optimized for protein expression in Escherichia coli; the gene also included a substitution of Q7K to prevent autoproteolysis. 2013 ACS chemical biology Method HIV Q7K 183 186 PR 48 56 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. 100 nM of 5'Cy3-Td43/Pd20 was incubated with 600 nM WT or N348I RT in a buffer containing 120 mM sodium cacodylate (pH 7), 20 mM NaCl, 6 mM MgCl2, and either of 5 muM ddATP or 1 muM EFdA-TP, to allow quantitative chain-termination. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Method HIV N348I 58 63 RT 64 66 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. 20 nM of purified Td31/Pd18-EFdA-MP or Tr31/Pd18-EFdA-MP were incubated with 60 nM WT, N348I, D67N/K70R/L210Q/T215F or D67N/K70R/L210Q/T215F/N348I RT in the presence of 3.5 mM ATP, 100 muM dATP, 0.5 muM dTTP, and 10 muM ddGTP in RT buffer and 10 mM MgCl2. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Method HIV D67N;D67N;K70R;K70R;L210Q;L210Q;N348I;T215F;T215F;N348I 94;119;99;124;104;129;141;110;135;87 98;123;103;128;109;134;146;115;140;92 RT;RT 147;229 149;231 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. RNase H assays were performed by incubating the RNA/DNA duplex5'Cy3-Tr35/Pd25 or 5'Cy3-Tr35/Pd25-ddAMP or 5'Cy3-Tr35/Pd25-EFdA-MP (50 nM) with WT or N348I RT (50 nM) in RT buffer at 37 C with MgCl2 (6 mM). 2012 Cellular and molecular biology (Noisy-le-Grand, France) Method HIV N348I 149 154 RT;RT 155;169 157;171 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. A previously published standardized adherence questionnaire (PACTG P1042S) was used at the time of cross-sectional analysis to systematically measure adherence based on information provided by parents and caregivers. 2013 BMC infectious diseases Method HIV P1042S 67 73 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The OLA was conducted according to the NIH protocol for mutations at HIV-1B protease positions D30N, I50V, V82A, V82S, V82T, I84V, N88D, and L90M as well as reverse transcriptase positions K103N, Y181C, K65R, T215F, T215Y, M184V, and Q151M. 2013 BMC infectious diseases Method HIV D30N;I50V;I84V;K103N;K65R;L90M;M184V;N88D;Q151M;T215F;T215Y;V82A;V82S;V82T;Y181C 95;101;125;189;203;141;223;131;234;209;216;107;113;119;196 99;105;129;194;207;145;228;135;239;214;221;111;117;123;201 RT;PR 157;76 178;84 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. In order to prevent PR autoproteolysis, a PR clone (Genbank HIVHXB2CG) engineered with five mutations (Q7K, L33I, L63I, C67A and C95A) was used as a template. 2013 Journal of medicinal chemistry Method HIV C67A;C95A;L33I;L63I;Q7K 120;129;108;114;103 124;133;112;118;106 PR;PR 20;42 22;44 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutants (R8Q, D30N, I50V, I54M and V82A) were generated by using the Quick-Change mutagenesis kit (Stratagene, La Jolla, CA). 2013 Journal of medicinal chemistry Method HIV D30N;I50V;I54M;R8Q;V82A 14;20;26;9;35 18;24;30;12;39 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Tenofovir-associated resistance mutations included K65R, T69 insertion, K70E and >=3 thymidine-analogue mutations (TAMs; M41L, D67N, K70R, L210W, T215F/Y, K219Q/E), inclusive of either M41L or L210W. 2012 Journal of the International AIDS Society Method HIV D67N;K219E;K219Q;K65R;K70E;K70R;L210W;L210W;M41L;M41L;T215F;T215Y 127;155;155;51;72;133;139;193;121;185;146;146 131;162;162;55;76;137;144;198;125;189;153;153 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Average linkage hierarchical agglomerative cluster analysis was performed to investigate if the protease mutations pairwise associated with the L76V mutation raised in specific evolutionary pathways, as previously described. 2013 PloS one Method HIV L76V 144 148 PR 96 104 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Frequency of the L76V mutation was surveyed in the clinical laboratory database of 2 clinical centers in Paris, France (Pitie-Salpetriere and Bichat-Claude Bernard Hospitals) and 1 in Rome, Italy (University of Rome "Tor Vergata"). 2013 PloS one Method HIV L76V 17 21 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In our study, samples with at least one of the major PI RAM of the IAS-USA list as follows: D30N, V32I, M46I/L, I47A/V, G48V, I50L/V, I54L/M, Q58E, T74P, L76V, V82A/F/L/T/S, N83D, I84V, N88S, L90M were considered as PI-resistant issued from PI-experienced patients. 2013 PloS one Method HIV D30N;G48V;I47A;I47V;I50L;I50V;I54L;I54M;I84V;L76V;L90M;M46I;M46L;N83D;N88S;Q58E;T74P;V32I;V82A;V82F;V82L;V82S;V82T 92;120;112;112;126;126;134;134;180;154;192;104;104;174;186;142;148;98;160;160;160;160;160 96;124;118;118;132;132;140;140;184;158;196;110;110;178;190;146;152;102;172;172;172;172;172 PI;PI;PI 53;216;241 55;218;243 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In the case of multiple samples from the same patient we only taking into account the first chronological sample harboring the L76V mutation. 2013 PloS one Method HIV L76V 127 131 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The association of the L76V mutation with other PI RAM was assessed in a subset of 1,956 subtype B and 481 subtypes "non-B" sequences obtained from patients failing their last PI-based regimen, with a full-length protease sequence available at the time of failure, including sequences without L76V mutation. 2013 PloS one Method HIV L76V;L76V 23;293 27;297 PR;PI;PI 213;48;176 221;50;178 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. To identify significant patterns of pairwise correlations between the L76V mutation and specific PI RAM observed in isolates from PI-experienced patients, we calculated the binomial correlation coefficient (phi) and its statistical significance for each pair of mutations. 2013 PloS one Method HIV L76V 70 74 PI;PI 97;130 99;132 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. The R332G, R335G and R332G-R335G mutations were described before. 2013 Virus research Method HIV R332G;R332G;R335G;R335G 4;21;11;27 9;26;16;32 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Briefly, murine leukemia virus envelope-pseudotyped viruses bearing the integrase H51Y and R263K mutations and a luciferase reporter gene were used to inoculate human embryonic kidney HEK-293 cells. 2013 Retrovirology Method HIV H51Y;R263K 82;91 86;96 IN;Env 72;31 81;39 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. pNL4.3IN(R263K) has been described previously . 2013 Retrovirology Method HIV R263K 9 14 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. To study the H51Y mutation and the H51Y/R263K combination, pNL4.3IN(H51Y) and pNL4.3IN(H51Y/R263K) were generated by site-directed mutagenesis using H51Y primers (sense: 5'-CTAAAAGGGGAAGCCATGTATGGACAAGTAGACTGTA-3' and antisense: 5'-TACAGTCTACTTGTCCATACATGGCTTCCCCTTTTAG-3'), and the QuickChange II XL Site-Directed mutagenesis kit (Stratagene). 2013 Retrovirology Method HIV H51Y;H51Y;H51Y;H51Y;H51Y;R263K;R263K 13;35;68;87;149;40;92 17;39;72;91;153;45;97 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. In particular for mutations M41L, M184V, and T215Y there are differences in Phenosense predictions compared with AVG. 2013 PLoS computational biology Method HIV M184V;M41L;T215Y 34;28;45 39;32;50 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Mutant HIV-1 group O RTs bearing the substitution D443N were obtained with the mutagenic primers 5'-GAAACCTATTATGTAAATGGAGCAGCTA-3' and 5'-TAGCTGCTCCATTTACATAATAGGTTTC-3'. 2013 Nucleic acids research Method HIV D443N 50 55 RT 21 24 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. O_WT RT and mutant derivatives V75I, V75I/E478Q and E478Q were obtained as previously described. 2013 Nucleic acids research Method HIV E478Q;E478Q;V75I;V75I 42;52;31;37 47;57;35;41 RT 5 7 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The amino acid change E478Q was introduced in the BH10 RT by using the mutagenic primers 5'-AAATCAGAAAACTCAGTTACAAGCAA-3' and 5'-TTGCTTGTAACTGAGTTTTCTGATTT-3'. 2013 Nucleic acids research Method HIV E478Q 22 27 RT 55 57 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The templates used were derivatives of the plasmid p66RTB containing the wild-type RT-coding sequences of the HIV-1BH10 (BH10) strain, an HIV-1ESP49 group O isolate or a previously described derivative of this clone with the V75I substitution. 2013 Nucleic acids research Method HIV V75I 225 229 RT 83 85 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Cells were plated in 12-well plates at 3x105 cells/well and infected with HIV-1NL-GFP WT or V86M vectors. 2013 Retrovirology Method HIV V86M 92 96 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. It was also assumed that chemical shifts for G89 in 15 N HIV1caN V86M did not change dramatically. 2013 Retrovirology Method HIV V86M 65 69 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. pMIP-TRIM5alphahu with the mutation R332G-R335G has been described, and additional mutants have been described as well. 2013 Retrovirology Method HIV R332G;R335G 36;42 41;47 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Uniformly 15 N-labeled CAN domain of HIV1 V86M (15 N HIV1caN V86M) was expressed and purified as per 15 N HIV1caN. 2013 Retrovirology Method HIV V86M 61 65 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Gp120 (WT and S375A) was immobilized on a CM5 chip using standard NHS/amine conjugation. 2013 Biochemistry Method HIV S375A 14 19 gp120 0 5 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. The S375A mutation was produced and purified as reported previously . 2013 Biochemistry Method HIV S375A 4 9 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The envs encoding the gp160 sequences corresponding to strains 14/00/4 and CM243(N610Q) were cloned into pRepX following similar procedures. 2013 PloS one Method HIV N610Q 81 86 gp160;Env 22;4 27;8 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. There were five groups of three animals each: the groups were wild type gp140 (CM243), N610/615/624/636Q, N615Q, N610/615Q and N610Q. 2013 PloS one Method HIV N610Q;N615Q 127;106 132;111 gp140 72 77 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Seven stabilized (Q7K, L33I, L63I) and inactive (D25N) constructs (Bsi) with engineered labeling sites (K55C) were made using the QuikChange site-directed mutagenesis kit by Stratagene: D30N, M36I, A71V, D30N/M36I, D30N/A71V, M36I/A71V, and D30N/M36I/A71V. 2013 Biochemistry Method HIV A71V;D30N;M36I;A71V;A71V;A71V;D25N;D30N;D30N;D30N;K55C;L33I;L63I;M36I;M36I;M36I;Q7K 251;241;246;198;220;231;49;186;204;215;104;23;29;192;209;226;18 255;245;250;202;224;235;53;190;208;219;108;27;33;196;213;230;21 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The buffer pH used for wild-type (WT) subtype B (Bsi), D30N, M36I, A71V, D30N/M36I, D30N/A71V, M36I/A71V, and D30N/M36I/A71V, respectively are as follows: 8.85, 9.00, 8.82, 8.80, 8.95, 8.98, 8.85, and 8.88. 2013 Biochemistry Method HIV A71V;D30N;M36I;A71V;A71V;A71V;D30N;D30N;D30N;M36I;M36I;M36I 120;110;115;67;89;100;55;73;84;61;78;95 124;114;119;71;93;104;59;77;88;65;82;99 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The C67A and C95A mutations have been utilized in numerous X-ray crystallography studies and do not alter kinetic parameters, protein stability or dimer dissociation compared to the unmutated sequence. 2013 Biochemistry Method HIV C67A;C95A 4;13 8;17 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Phytohemagglutinin-stimulated PBMCs were infected with equivalent amounts of wild type (WT) and K601D-mutated HIV-1AD8 (according to RT activity) in parallel and maintained in culture for 10 days. 2013 PLoS pathogens Method HIV K601D 96 101 RT 133 135 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Sequential passage of cell-free K601D virus in PBMC. 2013 PLoS pathogens Method HIV K601D 32 37 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Wild type, T138N/L494I/K601N and DeltaN139INN/K601N virus stocks were adjusted such that ~2x106 relative light units (RLU) were obtained following a 48 h-infection of TZM-bl cells, a HeLa cell line expressing CD4 and CCR5 and harbouring integrated copies of the luciferase and beta-galactosidase genes under control of the HIV-1 promoter (obtained from J. 2013 PLoS pathogens Method HIV K601N;L494I;T138N;K601N 23;17;11;46 28;22;16;51 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. A vesicular stomatitis virus (VSV-G) expression vector was co-transfected with following plasmids (WT, DeltaVpu, L30E and L30E-DeltaVpu) in 3:1 ratio in 293T cells using Lipofectamine method. 2013 PloS one Method HIV L30E;L30E 113;122 117;126 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Molecular variants of pNL-AD8 (WT), L30E, DeltaVpu and L30E-DeltaVpu were further constructed by converting the env start codon into a stop codon (ATG to TAA) to give rise WTDeltaEnv, L30EDeltaEnv, DeltaVpuDeltaEnv and L30E-DeltaVpuDeltaEnv backbones, respectively. 2013 PloS one Method HIV L30E;L30E;L30E 36;55;219 40;59;223 Env 112 115 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. The point substitution (L30E) in gag matrix (MA) was introduced by PCR using internal primers carrying specific L30E substitution and outer primers having unique 5' BssHII and 3' SphI restriction sites. 2013 PloS one Method HIV L30E;L30E 24;112 28;116 Matrix;Gag;Matrix 37;33;45 43;36;47 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. These molecular constructs have been referred as DeltaVpu and L30E-DeltaVpu throughout the study. 2013 PloS one Method HIV L30E 62 66 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. To introduce Vpu start codon mutation in pNL-AD8 wild-type (WT) and pNL-AD8L30E, internal primer pair was designed containing a single nucleotide substitution replacing ATG (methionine) with ATA (isoleucine) and outer primer pair containing 5' EcoRI and 3' BamHI restriction sites. 2013 PloS one Method HIV L30E 75 79 Vpu 13 16 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. CHO cells expressing hDAT and Y470H-hDAT were plated on 6 well plates at a density of 105 cells/well. 2013 Journal of neuroimmune pharmacology Method HIV Y470H 30 35 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. For the competitive inhibition experiment, cells transfected with hDAT and Y470H-hDAT were incubated in KRH buffer containing 50 mul of [3H]WIN 35,428 (5 nM, final concentration, specific activity, 85 Ci/mmol) and ZnCI2 (10 muM) using our published method. 2013 Journal of neuroimmune pharmacology Method HIV Y470H 75 80 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Haley E Melikian, University of Massachusetts) was used as a template to generate Y470H-hDAT using a QuikChange site-directed mutagenesis Kit (Agilent Tech, Santa Clara CA). 2013 Journal of neuroimmune pharmacology Method HIV Y470H 82 87 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Mutation in hDAT (tyrosine to histidine, Y470H-hDAT) was generated based on WT hDAT sequence (NCBI, cDNA clone MGC:164608 IMAGE:40146999) by site-directed mutagenesis. 2013 Journal of neuroimmune pharmacology Method HIV Y470H 41 46 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To determine the effect of Tat on DA uptake, cells transfected with WT or Y470H-hDAT were preincubated with each concentration of [3H]DA in the presence or absence of the concentrations of released Tat or Tat1-86 (350 nM). 2013 Journal of neuroimmune pharmacology Method HIV Y470H 74 79 Tat;Tat;Tat 27;198;205 30;201;208 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To determine whether decreased DA uptake in Y470H-hDAT is due to a reduction of cell surface DAT, biotinylation assays were performed as described previously. 2013 Journal of neuroimmune pharmacology Method HIV Y470H 44 49 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To determine whether mutated hDAT alters the maximal velocity (Vmax) or Michaelis-Menten constant (Km) of [3H]DA uptake, kinetic analyses were conducted in WT hDAT versus Y470H-hDAT in the presence or absence of recombinant Tat1-86. 2013 Journal of neuroimmune pharmacology Method HIV Y470H 171 176 Tat 224 227 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Twenty four hours after transfection, [3H]DA uptake in CHO cells transfected with wild type hDAT (WT hDAT) and Y470H-hDAT was performed in KRH buffer using a modified procedure as reported previously. 2013 Journal of neuroimmune pharmacology Method HIV Y470H 111 116 23660583 Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay. Amplicons from plasmid controls and specimens were tested in duplicate by SPX- and MPX-OLA using validated HIV subtype B- and subtype C-specific probes for detection of drug-resistance mutations K65R, M184V, K103N, V106M, Y181C, and G190A. 2013 Journal of virological methods Method HIV G190A;K103N;K65R;M184V;V106M;Y181C 233;208;195;201;215;222 238;213;199;206;220;227 23660583 Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay. Indeterminate results in SPX-OLA were defined in this study as reactions with a mutant OD less than the 2% mutant control (or 5% mutant control for subtype B K65R and Y181C) and a wild-type result less than 0.5 OD. 2013 Journal of virological methods Method HIV K65R;Y181C 158;167 162;172 23660583 Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay. Mutant was detected at >=2% for all codons tested except for K103N and Y181C, which had a lower limit of detection of 5% mutant. 2013 Journal of virological methods Method HIV K103N;Y181C 61;71 66;76 23660583 Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay. OLA probes used detected mutations associated with high-level drug-resistance in HIV pol encoding reverse transcriptase, including K65R and M184V selected by nucleoside reverse transcriptase inhibitors (NRTI), and K103N, V106M, Y181C, and G190A selected by non-nucleoside reverse transcriptase inhibitors (NNRTI) (Table 1). 2013 Journal of virological methods Method HIV G190A;K103N;K65R;M184V;V106M;Y181C 239;214;131;140;221;228 244;219;135;145;226;233 NNRTI;NRTI;RT;NNRTI;NRTI;Pol 257;158;98;306;203;85 293;190;119;311;207;88 23660583 Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay. The lower limit of detection of mutations across all codons tested was at a concentration of 2% except for subtype B K65R and Y181C, which were sensitive to a concentration of 5% mutant. 2013 Journal of virological methods Method HIV K65R;Y181C 117;126 121;131 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. Deoxyribopolynucleotides encoding inactivated IN (IN_in: D64V) and inactivated elvitegravir-resistant IN (IN_in_e3: H51Y, D64V, E92Q, S147G, E157Q, K160Q) were obtained by site-directed mutagenesis of IN_a gene. 2013 PloS one Method HIV D64V;D64V;E157Q;E92Q;H51Y;K160Q;S147G 57;122;141;128;116;148;134 61;126;146;132;120;153;139 IN;IN 46;102 48;104 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. For the detection of gp120, the membrane was incubated overnight at 4 C with 1 mug/ml M318T in 5% skim milk TBS-T. 2013 Frontiers in microbiology Method HIV M318T 86 91 gp120 21 26 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Mutants F277V and N295S, which have point mutations at amino acid residues 277 and 295 of Env, respectively, were constructed by PCR mutagenesis using the SIVmac316 plasmid as template. 2013 Frontiers in microbiology Method HIV F277V;N295S 8;18 13;23 Env 90 93 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Proviral DNA samples were extracted from cells using a QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany) after 8, 17, 20, 23, and 26 passages as well as from P26C cells obtained after 26 passages in the absence of Fab-B404. 2013 Frontiers in microbiology Method HIV P26C 160 164 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. The changes from phenylalanine (TTC) to valine (GTC) in F277V and asparagine (AAT) to serine (AGT) in N295S were introduced using primers F277VFw (5'-TTG GTT TGG CGT CAA TGG TAC TAG GGC-3'), F277VRv (5'-GTA CCA TTG ACG CCA AAC CAA G-3'), N295SFw (5'-GGC AAT AGT AGT AGA ACC ATA ATT AG-3'), and N295SRv (5'-AAT TAT GGT TCT ACT ACT ATT GCC-3'). 2013 Frontiers in microbiology Method HIV F277V;N295S 56;102 61;107 Tat 310 313 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. The Fab clones B404 and K8, isolated from an SIV-infected macaque, and murine MAb M318T were used to examine the sensitivity of viruses to antibody-mediated neutralization in TZM-bl cells as described previously. 2013 Frontiers in microbiology Method HIV M318T 82 87 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations that we assessed included K103N, Y181C, Y181I, G190A, G190S, V108I, Y188L, V106M, K103NS, K101E and G190E. 2013 Journal of the International AIDS Society Method HIV G190A;G190E;G190S;K101E;K103N;K103N;K103S;V106M;V108I;Y181C;Y181I;Y188L 112;165;119;155;91;147;147;140;126;98;105;133 117;170;124;160;96;153;153;145;131;103;110;138 NNRTI;NNRTI 0;48 36;53 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Nucleoside reverse transcriptase inhibitor (NRTI) mutations included in this analysis were as follows: M184V, M184I and M184V/I for lamivudine (3TC) and emtricitabine (FTC) resistance; K65R and K70E, associated with tenofovir (TDF) resistance; thymidine analogue mutations (TAMs) M41L, D67N, K70R, L210W, T215Y, T215F, K219Q, and K219 E, associated with resistance to multiple NRTIs; and multinucleoside mutations, including the 69 insertion complex and 151 complex. 2013 Journal of the International AIDS Society Method HIV D67N;K219E;K219Q;K65R;K70E;K70R;L210W;M184I;M184I;M184V;M184V;M41L;T215F;T215Y 286;330;319;185;194;292;298;120;110;103;120;278;312;305 290;336;324;189;198;296;303;127;115;108;127;284;317;310 NRTI;NRTI;NRTI 0;44;377 32;48;382 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Tenofovir resistance was defined as the presence of three or more TAMs, two of which included 41, 210, and 215 mutations; or the presence of K65R or 69 insertion site mutations. 2013 Journal of the International AIDS Society Method HIV K65R 141 145 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The structure corresponding to Y143R mutation of HIV-1 IN was obtained by modifying the WT structure of PFV IN bound to raltegravir (3OYA). 2013 Bioinformation Method HIV Y143R 31 36 IN;IN 55;108 57;110 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The X-ray crystal structures of WT, N224H (corresponding to N155H HIV-1 IN) and S217H (corresponding to G140S/Q148H HIV-1 IN) PFV IN/DNA intasome retrieved from Protein Data Bank with pdb code 3OYA, 3OYN, and 3OYL, respectively, were used for docking study. 2013 Bioinformation Method HIV G140S;N155H;N224H;Q148H;S217H 104;60;36;110;80 109;65;41;115;85 IN;IN;IN 72;122;130 74;124;132 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Subtype C allele-specific PCR (AS-PCR) assays were used to detect low-level K65R, K70E, and M184V mutations. 2013 Antiviral therapy Method HIV K65R;K70E;M184V 76;82;92 80;86;97 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. The delta cycle thresholds (DeltaCT) and the mutation frequency cutoffs were 8.0 and >=2% for K65R, 7.0 and >=0.3% for K70E, and 8.5 and >=0.5% for M184V. 2013 Antiviral therapy Method HIV K65R;K70E;M184V 94;119;148 98;123;153 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. We assessed for association between treatment site, duration on treatment, CD4 count, HIV RNA, prior NRTI exposure, sex, and age and presence of the K65R, M184V, or any major NNRTI mutation, based on the IAS-USA list of drug resistance mutations, using non-parametric methods; either the Wilcoxon rank sum test or Fisher's exact test, as appropriate. 2013 Antiviral therapy Method HIV K65R;M184V 149;155 153;160 NNRTI;NRTI 175;101 180;105 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. The expression plasmid pcDNA3.1day/V5HisTOPO (Invitrogen) and Env PCR products of CC1/85, BaL, III B, 85.6 viruses and selected mutants (V169M in V2, L317W in V3 and I408T in V4) in single, double and triple combinations were digested with HindIII and Xho1 restriction enzymes (Invitrogen), purified and ligated with T4 DNA Ligase (Invitrogen). 2013 AIDS research and therapy Method HIV I408T;L317W;V169M 166;150;137 171;155;143 Env 62 65 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. IID-IN mutants were introduced into a previously described vector encoding IN fused to YFP using QuickChange Lightening site-directed mutagenesis kit (Stratagene) and the following primers for each mutant: H12Y (Forward 5'-GCCCAAGATGAATATGAGAAATATCACAGTAATTGGAGAGCAATGGC-3') (Reverse 5'-GCCATTGCTCTCCAATTACTGTGATATTTCTCATATTCATCTTGGGC-3'); Q137R (Forward 5'-GGGCGGGAATCAAGCGGGAATTTGGAATTCCC-3') (Reverse 5'-GGGAATTCCAAATTCCCGCTTGATTCCCGCCC-3'); K71R (Forward 5'-CATTTAGAAGGACGAGTTATCCTGGTAGCAGTTCATGTAGCC-3') (Reverse 5'-GGCTACATGAACTGCTACCAGGATAACTCGTCCTTCTAAATG-3'); S147G (Forward 5'-CCCTACAATCCCCAAGGTCAAGGAGTAGTAGAATCTATG-3') (Reverse 5'-CATAGATTCTACTACTCCTTGACCGTTGGGATTGTAGGG-3'); K111E (Forward 5'-GGAAGATGGCCAGTAGAAACAATACATACAGACAATGGC-3') (Reverse 5'-GCCATTGTCTGTATGTATTGTTTCTACTGGCCATCTTCC-3'). 2013 Retrovirology Method HIV H12Y;K111E;K71R;Q137R;S147G 206;688;445;340;569 210;693;449;345;574 IN;IN 4;75 6;77 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. 100 nM of 5'-Cy3-Td43/Pd30 was incubated with 600 nM WT or K65R HIV-1 RT in a buffer containing 120 mM sodium cacodylate (pH 7), 20 mM NaCl, 6 mM MgCl2, and 1 muM EFdA-TP, to allow quantitative chain-termination. 2013 Retrovirology Method HIV K65R 59 63 RT 70 72 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. 20 nM of purified Td31/Pd18-P0-EFdA-MP was incubated at 37 C with 60 nM WT or K65R HIV-1 RT in the presence of 150 muM PPi, 100 muM dATP, 0.5 muM dTTP, and 10 muM ddGTP in RT buffer and 6 mM MgCl2. 2013 Retrovirology Method HIV K65R 78 82 RT;RT 89;172 91;174 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. 20 nM of purified Td31/Pd18-P0-EFdA-MP was incubated with 60 nM WT or K65R HIV-1 RT in the presence of 3.5 mM ATP, 100 muM dATP, 0.5 muM dTTP, and 10 muM ddGTP in RT buffer and 10 mM MgCl2. 2013 Retrovirology Method HIV K65R 70 74 RT;RT 81;163 83;165 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. A molecular model of EFdA-TP in the active site of K65R HIV RT was made using PDB ID 3JYT as a starting model (K65R HIV RT in complex with dATP). 2013 Retrovirology Method HIV K65R;K65R 51;111 55;116 RT;RT 60;120 62;122 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. K65R RT mutation was introduced by site-directed mutagenesis as described previously. 2013 Retrovirology Method HIV K65R 0 4 RT 5 7 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Reactions were carried out in RT buffer, 6 mM MgCl2, 100 nM Td26/Pd18-P5 or Td31/Pd18-P0 or Td31A/Pd21 (Table 3) and 10 nM WT or K65R HIV-1 RT in a final volume of 20 mul and stopped at indicated reaction times. 2013 Retrovirology Method HIV K65R 129 133 RT;RT 30;140 32;142 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Single nucleotide incorporation of dATP and EFdA-TP by WT and K65R RTs. 2013 Retrovirology Method HIV K65R 62 66 RT 67 70 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. SYBYL was also used to add the 2-fluoro and 4'-ethynyl groups to dATP in the K65R complex. 2013 Retrovirology Method HIV K65R 77 81 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. To monitor primer extension, the DNA/DNA hybrid (20 nM) was incubated at 37 C with WT or K65R HIV-1 RT (20 nM) in a buffer containing 50 mM Tris (pH 7.8) and 50 mM NaCl (RT buffer). 2013 Retrovirology Method HIV K65R 89 93 RT;RT 100;170 102;172 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. HIV-1 RT wild type (WT) protein (p66/p51 dimer, NL4-3), (specific activity = 5400 U/mg), patient RT isolate, K101E+G190S+M41L +T215Y, (D10) (specific activity = 7500 U/mg) were expressed and purified in our laboratory as previously described . 2013 Biochemistry Method HIV G190S;K101E;M41L;T215Y 115;109;121;127 120;114;125;132 RT;RT 6;97 8;99 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Similarly, PCR mutagenesis was used to create pNLdVdE-luc containing the RT mutation D443N. 2013 Retrovirology Method HIV D443N 85 90 RT 73 75 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The pNLdVdE-luc plasmid had the following CA amino acid substitutions introduced by via cloning from other HIV-1NL4-3 vectors or PCR mutagenesis: E45A, E45A/R132T, K203A, or 5Mut. 2013 Retrovirology Method HIV E45A;E45A;K203A;R132T 146;152;164;157 150;156;169;162 Capsid 42 44 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The vector was cotransfected with either WT or E45A pcHelpDeltaVif , a kind gift from Dr. 2013 Retrovirology Method HIV E45A 47 51 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. The 176-bp DNA fragments containing single mutations (I304V, F312W, T314A, E317D, or I318V) were subcloned into a cloning vector by overlapping PCR using primers tagged with a mutated tail. 2013 PloS one Method HIV E317D;F312W;I304V;I318V;T314A 75;61;54;85;68 80;66;59;90;73 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Different RT mutations at the same residue were pooled, including the NRTI-resistance mutations D67NG, K70EGQ, L74VI, M184VI, T215YF, K219QE and the NNRTI-resistance mutations K101EH, K103NS, Y188LCH, and G190ASEQ. 2013 PloS one Method HIV D67G;D67N;G190A;G190E;G190Q;G190S;K101E;K101H;K103N;K103S;K219E;K219Q;K70E;K70G;K70Q;L74I;L74V;M184I;M184V;T215F;T215Y;Y188C;Y188H;Y188L 96;96;205;205;205;205;176;176;184;184;134;134;103;103;103;111;111;118;118;126;126;192;192;192 101;101;213;213;213;213;182;182;190;190;140;140;109;109;109;116;116;124;124;132;132;199;199;199 NNRTI;NRTI;RT 149;70;10 154;74;12 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. The following non-polymorphic ARV-selected mutations were classified as drug resistance mutations (DRM): (i) the NRTI resistance mutations M41L, A62V, K65RN, D67NG, T69D, T69 insertions, T69 deletion, K70REGQ, L74VI, V75MT, F77L, Y115F, F116Y, Q151M, M184VI, L210W, T215YFSDCIV, and K219QENR; (ii) the NNRTI resistance mutations A98G, L100I, K101EPH, K103NS, V106MA, E138KGQ, V179DEFT, Y181CIV, Y188LCH, G190ASEQ, H221Y, P225H, F227LC, M230L, and K238T; and (iii) the PI resistance mutations L10F, V11I, L23I, L24I, D30N, L33F, M46IL, I47VA, G48VM, I50V, I54VMLATS, G73STCA, T74P, L76V, V82ATFSCML, I84V, N88DS, L89V, L90M. 2013 PloS one Method HIV A62V;A98G;D30N;D67G;D67N;E138G;E138K;E138Q;F116Y;F227C;F227L;F77L;G190A;G190E;G190Q;G190S;G48M;G48V;G73A;G73C;G73S;G73T;H221Y;I47A;I47V;I50V;I54A;I54L;I54M;I54S;I54T;I54V;I84V;K101E;K101H;K101P;K103N;K103S;K219E;K219N;K219Q;K219R;K238T;K65N;K65R;K70E;K70G;K70Q;K70R;L100I;L10F;L210W;L23I;L24I;L33F;L74I;L74V;L76V;L89V;L90M;M184I;M184V;M230L;M41L;M46I;M46L;N88D;N88S;P225H;Q151M;T215C;T215D;T215F;T215I;T215S;T215V;T215Y;T69D;T74P;V106A;V106M;V11I;V179D;V179E;V179F;V179T;V75M;V75T;V82A;V82C;V82F;V82L;V82M;V82S;V82T;Y115F;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 145;329;516;158;158;367;367;367;237;428;428;224;404;404;404;404;542;542;566;566;566;566;414;535;535;549;555;555;555;555;555;555;599;342;342;342;351;351;283;283;283;283;447;151;151;201;201;201;201;335;492;259;504;510;522;210;210;581;612;618;251;251;436;139;528;528;605;605;421;244;266;266;266;266;266;266;266;165;575;359;359;498;376;376;376;376;217;217;587;587;587;587;587;587;587;230;386;386;386;395;395;395 149;333;520;163;163;374;374;374;242;434;434;228;412;412;412;412;547;547;573;573;573;573;419;540;540;553;564;564;564;564;564;564;603;349;349;349;357;357;291;291;291;291;452;156;156;208;208;208;208;340;496;264;508;514;526;215;215;585;616;622;257;257;441;143;533;533;610;610;426;249;277;277;277;277;277;277;277;169;579;365;365;502;384;384;384;384;222;222;597;597;597;597;597;597;597;235;393;393;393;402;402;402 NNRTI;NRTI;PI 302;113;468 307;117;470 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. The following protease mutations were considered LPV/r-resistance mutations: L10F, L24I, V32I, L33F, M46IL, I47A, I50V, I54MLV, L76V, V82ATSFMC, I84V, L89V, L90M. 2013 PloS one Method HIV I47A;I50V;I54L;I54M;I54V;I84V;L10F;L24I;L33F;L76V;L89V;L90M;M46I;M46L;V32I;V82A;V82C;V82F;V82M;V82S;V82T 108;114;120;120;120;145;77;83;95;128;151;157;101;101;89;134;134;134;134;134;134 112;118;126;126;126;149;81;87;99;132;155;161;106;106;93;143;143;143;143;143;143 PR 14 22 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. The Q151M complex of mutations was defined as Q151M alone or in combination with one or more of the following mutations: A62V, V75I, F77L, and F116Y. 2013 PloS one Method HIV A62V;F116Y;F77L;Q151M;Q151M;V75I 121;143;133;4;46;127 125;148;137;9;51;131 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Thymidine analogue mutations (TAMs) were defined as M41L, D67NG, K70R, L210W, T215YF, and K219QE. 2013 PloS one Method HIV D67G;D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 58;58;90;90;65;71;52;78;78 63;63;96;96;69;76;56;84;84 23840857 Functional complementation of a model target to study Vpu sensitivity. Mutations that make the F-MLV Env binding defective (D84K) or fusion defective (L493V) were described earlier and the mutations were introduced into the F-MLV or F-MLV/GaLV construct by Overlap Extension PCR. 2013 PloS one Method HIV D84K;L493V 53;80 57;85 Env 30 33 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Underlined and in bold the mutated N276 D. 2013 PloS one Method HIV N276D 35 41 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Finally, we conducted sensitivity analyses removing patients with M184V, those with non-B subtype, and CD4 <200 cells/mm3 at the first resistance test, as these factors increase the likelihood that a patient had prior unrecorded ART exposure. 2013 The Journal of infectious diseases Method HIV M184V 66 71 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Mutations with individual frequencies >=10 (and T215F) were analyzed individually, and those with lower frequencies were grouped by drug class, with the exception of T215 revertants, which were grouped together. 2013 The Journal of infectious diseases Method HIV T215F 48 53 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Equations 1, 2, 3, 4 and 5 represent L90M frequency estimators trained from the V82A, I54V, A71V, M46I and I84V sets respectively. 2013 PloS one Method HIV A71V;I54V;I84V;L90M;M46I;V82A 92;86;107;37;98;80 96;90;111;41;102;84 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Evaluation revealed the models were good general predictors of L90M substitution frequency. 2013 PloS one Method HIV L90M 63 67 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. For each model, the frequency of L90M. 2013 PloS one Method HIV L90M 33 37 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Linear model to predict expected L90M frequency. 2013 PloS one Method HIV L90M 33 37 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Linear models for the estimation of L90M frequency given a set of frequencies for co-occurring mutations were constructed. 2013 PloS one Method HIV L90M 36 40 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. P(L90M) was calculated by a linear addition of the intercept together with the values produced by the other terms. 2013 PloS one Method HIV L90M 2 6 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The terms were chosen by observing frequently occurring combinations of PI resistance mutations listed in the hivDB together with L90M. 2013 PloS one Method HIV L90M 130 134 PI 72 74 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Where is the expected frequency of L90M and denote the mutation under which the model was trained. 2013 PloS one Method HIV L90M 36 40 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. KS13-IN-T174I, KS13-IN-L241A, and KS13-IN-K258A carrying point mutations in the IN coding region were generated by site-directed mutagenesis (Catalog No. 2013 PloS one Method HIV K258A;L241A;T174I 42;23;8 47;28;13 IN;IN;IN;IN 5;20;39;80 7;22;41;82 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. WT and IN-T174I mutant KS13/X4 viruses produced in the presence and absence of 1 microM GS-B were concentrated 40-fold. 2013 PloS one Method HIV T174I 10 15 IN 7 9 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Constructs used for the first time are PR20K7Q, PR20T26A, PRL33F/L63P, PRT26A/L33F/L63P, PRL33F/E34D/L63P, ScPR and ScPRD25N. 2013 Biochemistry Method HIV E34D;L33F;L33F;L63P;L63P;L63P 96;78;91;83;101;65 100;82;95;87;105;69 PR;PR;PR 58;71;89 60;73;91 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. Sequences were analyzed to identify mutations associated with reduced susceptibility to protease and RT inhibitors, as reported by the International AIDS Society-USA in 2010: RT-M41L, A62V, K65R, D67N, 69 insert, K70R, L74V,V75I, F77L, L100I, K101P, K103N, V106A, V106M, V108I, Y115F, F116Y, Q151M, Y181C, Y181I, M184V, M184I, Y188C, Y188L, Y188H, G190A, G190S, L210W, T215Y, T215F, K219Q, K219E and P225H; protease-D30N, V32I, M46I, M46L, I47A, I47V, G48V, I50L, I50V, I54L, I54M, Q58E, L76V, V82A, V82F, V82L, V82S, V82T, N83D, I84V, N88S and L90M. 2013 Journal of the International AIDS Society Method HIV A62V;D30N;D67N;F116Y;F77L;G190A;G190S;G48V;I47A;I47V;I50L;I50V;I54L;I54M;I84V;K101P;K103N;K219E;K219Q;K65R;K70R;L100I;L210W;L74V;L76V;L90M;M184I;M184V;M41L;M46I;M46L;N83D;N88S;P225H;Q151M;Q58E;T215F;T215Y;V106A;V106M;V108I;V32I;V75I;V82A;V82F;V82L;V82S;V82T;Y115F;Y181C;Y181I;Y188C;Y188H;Y188L 184;416;196;285;230;348;355;452;440;446;458;464;470;476;530;243;250;390;383;190;213;236;362;219;488;545;320;313;178;428;434;524;536;400;292;482;376;369;257;264;271;422;224;494;500;506;512;518;278;299;306;327;341;334 188;420;200;290;234;353;360;456;444;450;462;468;474;480;534;248;255;395;388;194;217;241;367;223;492;549;325;318;182;432;438;528;540;405;297;486;381;374;262;269;276;426;228;498;504;510;516;522;283;304;311;332;346;339 PR;PR;RT;RT 88;407;101;175 96;415;103;177 AIDS 149 153 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. A Q148R and Q148K IN-DNA model were built using the PFV DNA from 3S3M, however an inhibitor was purposely not docked into their active sites. 2013 PloS one Method HIV Q148K;Q148R 12;2 17;7 IN 18 20 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For the Q148R HIV-1 IN model, residue Q148 of the wild-type IN model was mutated to Arg, then its rotameric state set to match that of the equivalent Tn5 transposase residue, R322, from PDB entry 1MUS. 2013 PloS one Method HIV Q148R 8 13 IN;IN 20;60 22;62 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Here, however, the active-site loop, first helical turn of the alpha4 helix and Mg2+-bound conformations of D64, D116 and E152 were modeled from those of S217H PFV IN in PDB entry 3S3N. 2013 PloS one Method HIV S217H 154 159 IN 164 166 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. HIV-1 IN-DNA complexes were also constructed using the Q148H/G140S and N155H IN models, but here only DTG was docked into the active site. 2013 PloS one Method HIV G140S;N155H;Q148H 61;71;55 66;76;60 IN;IN 6;77 8;79 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Lastly, the N155H IN-DNA-DTG model was assembled based on the DTG-bound, PFV N224H intasome in 3S3O. 2013 PloS one Method HIV N155H;N224H 12;77 17;82 IN 18 20 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. More specifically, the PFV IN template included residues S209-K228 to model HIV-1 IN residues G140-K160, thus capturing the metal-bound conformation of HIV-1 IN residue E152 as well as the structural disturbances expected at the alpha4 helix due to the N155H substitution. 2013 PloS one Method HIV N155H 253 258 IN;IN;IN 27;82;158 29;84;160 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The N155H HIV-1 IN model was constructed with its active-site loop and a significant portion of the alpha4 helix modeled from those of N224H PFV IN in PDB entry 3S3O. 2013 PloS one Method HIV N155H;N224H 4;135 9;140 IN;IN 16;145 18;147 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Q148H/G140S HIV-1 IN model was constructed following the same approach used to build the wild-type IN model. 2013 PloS one Method HIV G140S;Q148H 10;4 15;9 IN;IN 22;103 24;105 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Q148H/G140S IN-DNA-DTG model was assembled based on the DTG-bound, PFV S217H intasome in 3S3N, with the exception of the two 3' adenylate conformations published for the PFV DNA. 2013 PloS one Method HIV G140S;Q148H;S217H 10;4;75 15;9;80 IN 16 18 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Q148K HIV-1 IN model was built in similar fashion to the Q148R IN model. 2013 PloS one Method HIV Q148K;Q148R 4;61 9;66 IN;IN 16;67 18;69 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The use of S217H PFV IN was important in modeling the structural disturbances expected at the active-site loop from the Q148H/G140S substitutions. 2013 PloS one Method HIV G140S;Q148H;S217H 126;120;11 131;125;16 IN 21 23 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. This positioned Q148R to form an ionic interaction with the side chain of E152 similar to the equivalent Tn5 transposase residues R322 and E326, respectively. 2013 PloS one Method HIV Q148R 16 21 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Wild-type, Q148R, Q148K, Q148H/G140S and N155H models of the HIV-1 IN dimeric catalytic core were constructed starting from the HIV-1 IN structure in 2B4J, which was taken from the RCSB Protein Data Bank (PDB; www.pdb.org). 2013 PloS one Method HIV G140S;N155H;Q148H;Q148K;Q148R 31;41;25;18;11 36;46;30;23;16 IN;IN 67;134 69;136 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. either PI/r or NNRTI) and the new emergence of M184V mutations. 2013 PloS one Method HIV M184V 47 52 NNRTI;PI 15;7 20;9 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. The latter mutation was selected due to its low genetic barrier and the widespread use of M184V selecting drugs in Switzerland. 2013 PloS one Method HIV M184V 90 95 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. LAINeffs -1, LAINeffs -13 and LAINefP72A/P75A infected groups each shared a common donor with the LAI infected group. 2013 Retrovirology Method HIV P75A 41 45 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. None of the groups (Naive, LAI, LAINeffs -1, LAINeffs -13 and LAINefP72A/P75A) had significantly different engraftment levels compared to any of the other groups (p >= 0.1535). 2013 Retrovirology Method HIV P75A 73 77 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Stocks of LAI, LAINeffs, LAINeffs -1, LAINeffs -13 and LAINefP72A/P75A were prepared and titered as we previously described. 2013 Retrovirology Method HIV P75A 66 70 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. The site directed mutations of nef in pLAINeffs -1, pLAINeffs -13 and pLAINefP72A/P75A were subcloned into pLXSN, a retroviral vector for transduction of CEM T cells and into pcDNA3.1 for transfection into 293T cells. 2013 Retrovirology Method HIV P75A 82 86 Nef 31 34 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. A recent kinetic study in the absence of a nucleic acid has experimentally demonstrated a reduced binding of nevirapine to RT by N348I mutation. 2014 Proteins Method HIV N348I 129 134 RT 123 125 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. However, crystal structure of RT-DNA-NVP and N348I/T369I RT-DNA-NVP did not contain active site metal ions (Mg2+), pertaining to the experimental observations that no metal ion binds to the catalytic aspartate when RT is complexed with an NNRTI. 2014 Proteins Method HIV N348I;T369I 45;51 50;56 NNRTI;RT;RT;RT 239;30;57;215 244;32;59;217 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The crystal structure of RT-DNA-NVP (PDB: 3V81) that represents a polymerase incompetent state served as a ternary complex for our simulation study, and the clinically relevant connection subdomain mutations N348I and T369I were introduced computationally into the crystal structure of RT-DNA-NVP complex to generate the starting model of the N348I/T369I RT-DNA-NVP complex. 2014 Proteins Method HIV N348I;N348I;T369I;T369I 208;343;218;349 213;348;223;354 Pol;RT;RT;RT 66;25;286;355 76;27;288;357 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The mutated residue Q258C and the nonstandard nucleotide bases engineered for cross-linking were reverted to standard residue and nucleotide, respectively. 2014 Proteins Method HIV Q258C 20 25 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. DeltaRT and DeltaIN infectious clones were generated by making mutant RT D185E, or IN D116N using site directed mutagenesis (Stratagene). 2013 Nature Method HIV D116N;D185E 86;73 91;78 IN;RT 83;70 85;72 24196705 HIV-1 evades innate immune recognition through specific cofactor recruitment. The CCR5-tropic Wild type NL4.3 (Ba-L Env) or NL4.3 (Ba-L Env) bearing CA mutations P90A or N74D were derived from an infectious clone of NL4.3 by cloning the Env gene from HIV-1 Ba-L between unique EcoR1 and BamH1 sites to replace the NL4.3 Env gene. 2013 Nature Method HIV N74D;P90A 92;84 96;88 Env;Env;Env;Env;Capsid 38;58;159;242;71 41;61;162;245;73 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. A pET11a plasmid containing DNA for a monomeric HIV-1 CA, p24-W184A/M185A, with a C-terminal His tag was transformed into Rosetta 2 (DE3) cells (EMD) for protein expression. 2013 Retrovirology Method HIV M185A;W184A 68;62 73;67 p24;Capsid 58;54 61;56 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Both CTD (W184A/M185A) protein and stapled peptides were exhaustively dialyzed against 25 mM sodium phosphate buffer (pH 7.3) prior to experimental measurements. 2013 Retrovirology Method HIV M185A;W184A 16;10 21;15 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Env pseudotyped viruses were generated by cotransfecting 293T cells with an Env-defective pNL4-3 derivative (pNL4-3/KFS) and HIV-1 Env expression vector pIIINL4env, pIIINL4env-V120Q/A327P, or VSV-G expression vector pHCMV-G. 2013 Retrovirology Method HIV A327P;V120Q 182;176 187;181 Env;Env;Env 0;76;131 3;79;134 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. In a typical experiment, the ITC injection syringe was loaded with 625 muM CTD (W184A/M185A) protein, dissolved in the dialysis buffer. 2013 Retrovirology Method HIV M185A;W184A 86;80 91;85 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. PBMCs isolated from healthy donors were activated by phytohemagglutinin (PHA) and were infected with RT-normalized WT- and V120Q/A327P mutant viruses and replication was carried out in the presence of 30 M NYAD-36, -66, or -67. 2013 Retrovirology Method HIV A327P;V120Q 129;123 134;128 RT 101 103 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Staple peptides were dissolved in 100% DMSO and titrated into the monomeric HIV-1 CA, p24-W184A/M185A, in a buffer containing 50 mM NaOAc [pH 5.5] 5 mM DTT with 10%D2O. 2013 Retrovirology Method HIV M185A;W184A 96;90 101;95 p24;Capsid 86;82 89;84 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. The binding affinity between CTD (W184A/M185A) and NYAD-36, NYAD-66 or NYAD-67 was measured by ITC at 30 C using a Microcal titration calorimeter (MicroCal VP-ITC). 2013 Retrovirology Method HIV M185A;W184A 40;34 45;39 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. The CTD mutant (W184A/M185A) was generated from pET14b-C-CA using Stratagene's QuikChange Site-Directed Mutagenesis Kit following the manufacture's protocol. 2013 Retrovirology Method HIV M185A;W184A 22;16 27;21 Capsid 57 59 24268781 Link between primate lentiviral coreceptor usage and Nef function. Mutations of I123L and L146F were inserted into the SIVmac239 Nef structure and displayed using the program PyMOL (http://www.pymol.org). 2013 Cell reports Method HIV I123L;L146F 13;23 18;28 Nef 62 65 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. All of these inactive PR variants have D25N mutation that has been shown to minimally alter the overall structure of the PR complexes. 2012 Journal of chemical theory and computation Method HIV D25N 39 43 PR;PR 22;121 24;123 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. For example, LP1'Fp1-p6D30N/N88D denotes a complex of D30N/N88D PR variant with the LP1T mutant of the p1-p6 cleavage site, where LP1'F refers to a Leu-to-Phe mutation at P1' position of the cleavage site. 2012 Journal of chemical theory and computation Method HIV D30N;D30N;N88D;N88D 23;54;28;59 27;58;32;63 Gag;Gag;PR 21;106;64 23;108;66 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. HIV-1 PR (WT, V82A, or D30N/N88D) and the cleavage site (AP2V, LP1'F, or SP3'N) variants in a PR:substrate complex are designated by a subscript and a superscript to the name of the cleavage site. 2012 Journal of chemical theory and computation Method HIV D30N;N88D;V82A 23;28;14 27;32;18 PR;PR 6;94 8;96 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The crystal structures of WTp1-p6WT and WTNC-p1WT and AP2VNC-p1V82A variants were used as the starting structures in the MD simulations (PDB ID: 1KJF, 1TSU, 1TSQ). 2012 Journal of chemical theory and computation Method HIV V82A 63 67 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. This D25N mutation is not associated with drug-resistance; therefore, we refer to D25N as WT throughout the paper for simplicity in nomenclature. 2012 Journal of chemical theory and computation Method HIV D25N;D25N 5;82 9;86 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Briefly, mutation-specific primers were designed for seven reverse transcriptase inhibitor resistance mutations, M41L, K65R, K70R, K103N, Y181C, M184V, and T215F/Y. 2013 PloS one Method HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y;Y181C 131;119;125;145;113;156;156;138 136;123;129;150;117;163;163;143 RT 59 80 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Fifty-five samples with protease M46I were obtained from 20 individuals and 22 samples with M46L were obtained from 12 individuals. 2013 PloS one Method HIV M46I;M46L 33;92 37;96 PR 24 32 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. For this study, new primers for the detection of M46I and M46L protease inhibitor mutations were constructed as described before. 2013 PloS one Method HIV M46I;M46L 49;58 53;62 PR 63 71 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Furthermore, to compensate for the spectrum of polymorphisms present, mixtures of three uniquely designed forward primers were required to detect M46L. 2013 PloS one Method HIV M46L 146 150 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. HXB2-M46I, HXB2-M46L and HXB2 (wild-type) plasmids were used in the preliminary selection of primer mixtures that provided the greatest sensitivity and specificity. 2013 PloS one Method HIV M46I;M46L 5;16 9;20 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In order to analyze the relationship between M46I/L-positive amplicon sequences and bulk sequences, we extended the M46I/L-positive amplicon by using the PRO2L reverse primer (Table S1B), which allowed sequencing from PR codon 47 to RT codon 36 of these M46I/L-positive amplicons (270 bp). 2013 PloS one Method HIV M46I;M46I;M46I;M46L;M46L;M46L 45;116;254;45;116;254 51;122;260;51;122;260 PR;RT 218;233 220;235 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In the case of L90M amplicon analysis, 209 bp DNA fragments extending from amino acid 20 in PR to amino acid 89 in PR were represented in the phylogenetic tree. 2013 PloS one Method HIV L90M 15 19 PR;PR 92;115 94;117 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M46I and M46L mutant clones for plasmid development were constructed by site-directed mutagenesis using HXB2 as a template. 2013 PloS one Method HIV M46L;M46I 9;0 13;4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M46I/L primers for real-time-PCR. 2013 PloS one Method HIV M46I;M46L 0;0 6;6 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. These constructs were used as positive control to verify the M46I/L primers and probes. 2013 PloS one Method HIV M46I;M46L 61;61 67;67 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. To evaluate cutoff values of M46I and M46L in patient samples, PR-RT sequences derived from ART-naive patients were analyzed by real-time PCR. 2013 PloS one Method HIV M46I;M46L;M46I;M46L 30;39;29;38 34;43;33;42 PR;RT 63;66 65;68 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. To evaluate whether additional information on resistance mutations could be gained from the real-time PCR assays, we performed bulk sequencing (BigDye reagent, Prism 3130xl analyzer, Applied Biosystems) of the products from M46I/L or L90M-specific reactions to assess mutation linkage. 2013 PloS one Method HIV L90M;M46I;M46L 234;224;224 238;230;230 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. To insert M46I or M46L mutations into HXB2, PCR with KODplus was performed using a pair of complementary primers (M46I-forward primer : GAA GAT GGA AAC CAA AAA TaA TAG GGG GAA TTc GAG G, M46L(ttg)-forward primer : GAA GAT GGA AAC CAA AAt TGA TAG GGG GAA TTG GAG G , M46L(ctg)-forward primer : GAA GAT GGA AAC CAA AAc TGA TAG GGG GAA TTG GAG G), and reverse primer : CTG GCA AAC TCA TTT CTT CTA ATA CTG TAT CAT CTG CTC C). 2013 PloS one Method HIV M46I;M46I;M46L;M46L;M46L 10;114;18;187;266 14;118;22;191;270 Tat 402 405 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Harvested cells containing Cul5-NTD (residues 1 to 393 with two point mutations, V341R, L345D, and) were lysed in lysis buffer (1X PBS and 0.25 mM TCEP). 2014 Retrovirology Method HIV L345D;V341R 88;81 93;86 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Plasmids were transformed or co-transformed into Escherichia coli NiCo21(DE3) cells(New England Biolabs C2529H) according to manufacturer's protocol. 2014 Retrovirology Method HIV C2529H 104 110 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Briefly, 30,000 cells per well were infected with the WT, M50I, R263K, or M50I/R263K viruses in the presence of serial dilutions of DTG, RAL, or EVG in 96-well plates (Corning). 2014 Retrovirology Method HIV M50I;M50I;R263K;R263K 58;74;64;79 62;78;69;84 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The Km values for the INBWT, INBM50I, INBR263K, INBM50I/R263K enzymes were 3.745, 8.997, 11.40 and 9.660, respectively. 2014 Retrovirology Method HIV R263K 56 61 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The pNL4.3INB(M50I) and pNL4.3INB(M50I/R263K) replication-competent HIV-1 plasmids were generated using the QuickChange II XL Site-Directed mutagenesis kit. 2014 Retrovirology Method HIV M50I;M50I;R263K 14;34;39 18;38;44 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The pNL4.3INB(R263K) plasmid has been described previously . 2014 Retrovirology Method HIV R263K 14 19 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The primers used for the M50I mutation were: sense, 5'-CTAAAAGGGGAAGCCATACATGGACAAGTAGACTG-3' and antisense, 5'-CAGTCTACTTGTCCATGTATGGCTTCCCCTTTTAG-3'. 2014 Retrovirology Method HIV M50I 25 29 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The strand-transfer activity of the wild-type, M50I, R263K, and M50I/R263K integrase subtype B proteins were measured using a microtiter plate assay as previously described . 2014 Retrovirology Method HIV M50I;M50I;R263K;R263K 47;64;53;69 51;68;58;74 IN 75 84 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. The double mutant E138K + Q148K was made by using the Q148K mutant and the appropriate oligonucleotide to introduce the second mutation, E138K. 2014 Journal of medicinal chemistry Method HIV E138K;E138K;Q148K;Q148K 18;137;26;54 23;142;31;59 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. The double mutant G140A + Q148K was made by using the Q148K mutant and the appropriate oligonucleotide to introduce the second mutation, G140A. 2014 Journal of medicinal chemistry Method HIV G140A;G140A;Q148K;Q148K 18;137;26;54 23;142;31;59 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. The double mutant G140S + Q148H was constructed by using the previously generated Q148H mutant and the appropriate oligonucleotide to introduce the second mutation, G140S. 2014 Journal of medicinal chemistry Method HIV G140S;G140S;Q148H;Q148H 18;165;26;82 23;170;31;87 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. The following sense with cognate antisense (not shown) oligonucleotides (Integrated DNA Technologies, Coralville, IA) was used in the mutagenesis: G118R, 5'-GTACATACAGACAATCGCAGCAATTTCACCAGTAC-3'; E138K, 5'-GGCGGGGATCAAGCAGAAATTTGGCATTCCCTA-3'; G140A, 5'-GGGGATCAAGCAGGAATTTGCCATTCCCTACAATC-3'; G140S, 5'-GGGGATCAAGCAGGAATTTAGCATTCCCTACAATC-3'; Y143R, 5'-GCAGGAATTTGGCATTCCCCGCAATCCCCAAAGTCAAGGA-3'; Q148H, 5'-CATTCCCTACAATCCCCAAAGTCATGGAGTAATAGAATCTA-3'; Q148K, 5'-CATTCCCTACAATCCCCAAAGTAAAGGAGTAATAGAATCTATGAA-3'; and N155H, 5'-CCAAAGTCAAGGAGTAATAGAATCTATGCATAAAGAATTAAAGAAAATTATAGGACA-3'. 2014 Journal of medicinal chemistry Method HIV E138K;G118R;G140A;G140S;N155H;Q148H;Q148K;Y143R 197;147;245;295;520;400;456;345 202;152;250;300;525;405;461;350 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Using that construct as the wild-type template, we prepared the following IN-resistant mutants via the QuikChange II XL (Stratagene, La Jolla, CA) site-directed mutagenesis protocol: G118R, Y143R, Q148H, Q148K, N155H, G140S + Q148H, G140A + Q148K, and E138K + Q148K. 2014 Journal of medicinal chemistry Method HIV E138K;G118R;G140A;G140S;N155H;Q148H;Q148H;Q148K;Q148K;Q148K;Y143R 252;183;233;218;211;197;226;204;241;260;190 257;188;238;223;216;202;231;209;246;265;195 IN;Capsid 74;143 76;145 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. 24 hours later, the confluent cells were incubated with 10 ml of Env- HIV-1, pseudotyped with VSV G, and bearing either WT or A92E mutant CA, in presence of 5 muM CsA for 30 min at 4 C and then shifted to 37 C. 2014 Retrovirology Method HIV A92E 126 130 Env;Capsid 65;138 68;140 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Hela clone 3D and MT4 cells expressing hT5Cyp or hT5Cyp-H436Q were seeded onto T75 flasks. 2014 Retrovirology Method HIV H436Q 56 61 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. hT5Cyp and hT5Cyp-H436Q viral vectors were previously described. 2014 Retrovirology Method HIV H436Q 18 23 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. p8.9NdSB bearing G89V, G89V/A92E, P90A, P90A/A92E, A92E, A92E/A105T and A105T in the CA sequence were previously described. 2014 Retrovirology Method HIV A105T;A105T;A92E;A92E;A92E;A92E;G89V;G89V;P90A;P90A 62;72;28;45;51;57;17;23;34;40 67;77;32;49;55;61;21;27;38;44 Capsid 85 87 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. First stage PCR for the construction of the G196R and K275R double mutant was performed using the completed K275R construct as the DNA template and the G196R-mutF/mutR mutagenesis primers. 2014 PloS one Method HIV G196R;G196R;K275R;K275R 44;152;54;108 49;157;59;113 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. First stage PCR utilized the wild type 5'-RT-SHIV half clone as the DNA template for construction of both the G196R mutant and the K275R mutant; the mutagenesis primers were G196R:mutF/mutR and K275R:mutF/mutR respectively. 2014 PloS one Method HIV G196R;G196R;K275R;K275R 110;174;131;194 115;179;136;199 RT 42 44 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Infectious RT-SHIVs containing G196R, K275R, and both G196R and K275R, mutations in reverse transcriptase (RT) were produced by site-directed PCR mutagenesis of the RT-SHIV 5'-half clone. 2014 PloS one Method HIV G196R;G196R;K275R;K275R 31;54;38;64 36;59;43;69 RT;RT;RT;RT 84;11;107;165 105;13;109;167 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. RT-SHIV used in this study contained the T to C substitution at position 8 of the SIV tRNA primer binding site, which is necessary for rapid replication of RT-SHIV. 2014 PloS one Method HIV T8C 41 74 RT;RT 0;156 2;158 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. To evaluate stability of the G196R mutation, RT-SHIV-196R was serially passaged in rhesus PBMC. 2014 PloS one Method HIV G196R 29 34 RT 45 47 24520823 Human protein Staufen-2 promotes HIV-1 proliferation by positively regulating RNA export activity of viral protein Rev. One such hStau-2 mutant, carrying the mutations Q314R, A318F and K319E, was found defective in binding Rev. 2014 Retrovirology Method HIV A318F;K319E;Q314R 55;65;48 60;70;53 Rev 103 106 24520823 Human protein Staufen-2 promotes HIV-1 proliferation by positively regulating RNA export activity of viral protein Rev. The mutant region containing Q314R, A318F and K319E mutations were generated by overlap PCR using Stau-2Mut FP and Stau-2Mut RP (Additional file 7: Table S1) and cloned into SalI and XbaI site of pCMV-Sport 1 (Invitrogen, USA). 2014 Retrovirology Method HIV A318F;K319E;Q314R 36;46;29 41;51;34 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Among the protease inhibitor resistance mutations, the I50V, I54M, and I84V were associated with resistance to darunavir. 2014 AIDS (London, England) Method HIV I50V;I54M;I84V 55;61;71 59;65;75 PR 10 18 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. In this study, HIV-2 resistance mutations were identified using the list generated by the 'Collaborative HIV and Anti-HIV Drug Resistance Network', leading to the following mutations in reverse transcriptase - K65R, D67G/N, N69S/T, K70N/R, L74V, V111I, Y115F, M184I/V, Q151M, S215A/C/F/L/Y, K223R; and in protease - V47A, G48V, I50V, I54L/M, V62A, I82F, I84V, L90M, L99F. 2014 AIDS (London, England) Method HIV D67G;D67N;G48V;I50V;I54L;I54M;I82F;I84V;K223R;K65R;K70N;K70R;L74V;L90M;L99F;M184I;M184V;N69S;N69T;Q151M;S215A;S215C;S215F;S215L;S215Y;V111I;V47A;V62A;Y115F 216;216;322;328;334;334;348;354;291;210;232;232;240;360;366;260;260;224;224;269;276;276;276;276;276;246;316;342;253 222;222;326;332;340;340;352;358;296;214;238;238;244;364;370;267;267;230;230;274;289;289;289;289;289;251;320;346;258 RT;PR 186;305 207;313 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Parental and engineered cells were challenged with HIV-1luc, HIV-1luc with the N74D capsid mutation, FIVluc, and NB-MLVluc at two vector inputs. 2014 PLoS pathogens Method HIV N74D 79 83 Capsid 84 90 24603872 Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy. Patients with more than one darunavir resistance-associated mutation or with known major integrase resistance-associated mutations (N155H, Q148H/R/K, Y143C/R, and G140S) were excluded from the study. 2014 PloS one Method HIV G140S;N155H;Q148H;Q148K;Q148R;Y143C;Y143R 163;132;139;139;139;150;150 168;137;148;148;148;157;157 IN 89 98 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. A92E CA mutant was subcloned from HIV-1 proviral DNA construct R9 by transfer of ApaI-SpeI or BssHII-SpeI restriction fragments into HIV-GFP, an envelope-defective pNL4-3-based HIV-1 reporter virus clone encoding green fluorescent protein (GFP) in place of Nef. 2014 PloS one Method HIV A92E 0 4 Env;Nef;Capsid 145;257;5 153;260;7 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. The next day, monolayers were inoculated with VSV-G-pseudotyped HIV-GFP-A92E in the presence or absence of CsA (5 muM). 2014 PloS one Method HIV A92E 72 76 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Crystals of PRP51 (including the D25N mutation) complexed with clinical inhibitors DRV and SQV were obtained by the hanging-drop vapor-diffusion method at RT using 24 well VDX plates (Hampton Research, Aliso Viejo, CA, USA). 2014 ACS chemical biology Method HIV D25N 33 37 Capsid;PR;RT 215;12;155 217;14;157 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Screening Kit I solutions (Hampton Research, Aliso Viejo, CA, USA) gave good crystals of PRP51 complexed with DRV (0.1 M HEPES sodium pH 7.5, 0.8 M potassium sodium tartrate tetrahydrate) and crystals of PRP51-D25N grown in the presence of SQV (0.1 M imidazole pH 6.5, 1.0 M sodium acetate trihydrate). 2014 ACS chemical biology Method HIV D25N 210 214 Capsid;PR;PR 58;89;204 60;91;206 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The PRP51 construct contains 14 mutations (L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, and L89M) plus three other mutations Q7K to minimize autoproteolysis and C67A and C95A to prevent cysteine-induced aggregation. 2014 ACS chemical biology Method HIV C67A;C95A;I15V;I54M;I84V;K20R;K70Q;L10I;L24I;L33F;L63P;L89M;M36I;M46L;Q7K;V32I;V82I 194;203;49;91;115;55;103;43;61;73;97;125;79;85;158;67;109 198;207;53;95;119;59;107;47;65;77;101;129;83;89;161;71;113 PR 4 6 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The structure coordinates and factors have been deposited in the Protein Data Bank with access codes 4NPT for PRP51-D25N-DRV and 4NPU for PRP51-D25N. 2014 ACS chemical biology Method HIV D25N;D25N 116;144 120;148 PR;PR 110;138 112;140 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. To eliminate autoproteolysis, the inactivating mutation of D25N was introduced using the QuikChange II Site-Directed Mutagenesis Kit and confirmed by DNA sequencing. 2014 ACS chemical biology Method HIV D25N 59 63 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. South San Francisco CA) for drug susceptibility profiles; an AS-PCR-based quantitative minor variant assay (qMVA) as the primary analysis targeting rt K65R, K70E, M184V, and M184I; and 454 GS-FLX Titanium single-amplicon deep sequencing (Roche Applied Sciences, Pleasanton, CA) for confirmatory analysis. 2014 The Journal of infectious diseases Method HIV K65R;K70E;M184I;M184V 151;157;174;163 155;161;179;168 Capsid;Capsid;RT 20;274;148 22;276;150 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. We defined the BCO for each DR site, template (TRUGENE or HBA), and assay primer set (qMVA and 454 sequencing) using panels of 12 subtype B and 9 subtype C samples from individuals infected prior to the general availability of antiretroviral drugs, selecting for K65R, K70E, and M184V/I (Supplementary Methods). 2014 The Journal of infectious diseases Method HIV K65R;K70E;M184I;M184V 263;269;279;279 267;273;286;286 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. RPV resistance-associated mutations were divided into key resistance mutations (K101E/P, E138A/G/K/Q/R, V179L,Y181C/I/V, Y188L, H221Y, F227C and M230I/L) based on the IAS-USA drug resistance mutations list update 2013 and potential drug resistance mutations (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the clinical trial and in vitro data with the exclusion of mutations not associated with virological failure. 2014 Journal of the International AIDS Society Method HIV V179L;Y181C;Y181I;Y181V;E138A;E138G;E138K;E138Q;E138R;E138S;F227C;F227L;G190A;G190E;G190S;H221Y;K101E;K101H;K101P;K101T;L100I;M230I;M230L;M230V;V179D;V179F;V179G;V179T;Y188L 104;111;110;110;89;89;89;89;89;275;135;306;295;295;295;128;80;266;80;266;259;145;145;316;282;282;282;282;121 109;119;119;119;102;102;102;102;102;280;140;311;304;304;304;133;87;273;87;273;264;152;152;321;293;293;293;293;126 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. A Glu to Cys (E275C) mutation was introduced into the YU-2 gp120 backbone using the QuikChange site-directed mutagenesis protocol (Stratagene). 2014 Biochemistry Method HIV E275C 14 19 gp120 59 64 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Maleimide-PEG2-biotin (hereafter MPB, Pierce) was used as a general-purpose sulfhydryl-directed biotinylation reagent and reacted in parallel with and similar to AE21 with WT or E275C gp120. 2014 Biochemistry Method HIV E275C 178 183 gp120 184 189 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Purified gp120 (E275C or WT) was exchanged into reaction buffer [filtered and degassed 0.1 M PBS (pH 6.9) with 10 mM EDTA]. 2014 Biochemistry Method HIV E275C 16 22 gp120 9 14 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The following primer set was used for E275C: 5'-GATCGTGATCCGGAGCTGTAACTTCACCAACAACG-3' (forward) and 5'-CGTTGTTGGTGAAGTTACAGCTCCGGATCACGATC-3' (reverse). 2014 Biochemistry Method HIV E275C 38 43 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. To control for the different amounts of product captured on such a surface and E275C-immobilized surfaces, signals were normalized to the maximal signal from injection of 200 nM mAb D7324. 2014 Biochemistry Method HIV E275C 79 84 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Plasmids phVif G84A, G84D, V85S, S86A, I87A, E88A, W89A, G84A/SIEW86-89AAAA(84/86-89), E88A/W89A(88/89), L102A, A103S, D104A, Q105A, L106A and I107A were derived from phVif-HA by site-directed mutagenesis. 2014 PloS one Method HIV A103S;D104A;E88A;E88A;G84A;G84A;G84D;I107A;I87A;L102A;L106A;Q105A;S86A;V85S;W89A;W89A 112;119;45;87;15;57;21;143;39;105;133;126;33;27;51;92 117;124;49;91;19;61;25;148;43;110;138;131;37;31;55;96 24831260 Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. Sequences were assembled with Sequencher (version 4.9; Gene Codes Corp, Ann Arbor, Ml) and submitted to the Stanford University HIV Drug Resistance Database (version 6.3.0; http://hivdb.stanford.edu on August 21, 2013) to identify "major" INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, and N155H). 2015 Antiviral therapy Method HIV E92Q;G140S;N155H;Q148H;Q148K;Q148R;S147G;T66I;Y143C;Y143H;Y143R 262;268;308;293;293;293;286;256;275;275;275 266;273;313;302;302;302;291;260;284;284;284 INSTI 239 244 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. The A128T CCD protein was concentrated to 8.5 mg/ml and crystallized at room temperature (20 C) using the hanging drop vapor diffusion method. 2014 PLoS pathogens Method HIV A128T 4 9 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. The HIV-1 IN CCD (residues 50-212 containing the F185K substitution) and its A128T mutant were expressed and purified as described. 2014 PLoS pathogens Method HIV A128T;F185K 77;49 82;54 IN 10 12 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. The structures were refined to 2.05 A for KF115 bound to the CCD, 2.20 A for KF116 bound to the CCD, and 2.37 A for KF116 bound to the A128T CCD. 2014 PLoS pathogens Method HIV A128T 135 140 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. BG505 SOSIP.664 gp140 was constructed by introducing several sequence modifications (all numbering is based on the HxB2 sequence): A501C and T605C, to create a disulfide bond between gp120 and gp41ECTO); I559P in gp41ECTO, to increase trimer stability; REKR (HXB2 Env amino-acid residues 508-511) changed to RRRRRR (R6) at the cleavage site between gp120 and gp41ECTO, to promote proteolytic processing by furin); T332N in gp120, to allow the binding of bNAbs that depend on glycan-332; a stop codon at gp41ECTO residue 664, to improve trimer solubility and homogeneity). 2014 Retrovirology Method HIV A501C;I559P;T332N;T605C 131;204;414;141 136;209;419;146 gp41;gp41;gp41;gp41;gp120;gp120;gp120;gp140;Env 193;213;359;503;183;349;423;16;264 197;217;363;507;188;354;428;21;267 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Data on neutralization of BG505.T332N pseudovirus by IgG NAbs from previous studies and in addition by Fabs, obtained by the same method, were converted to logarithmic relative infectivities and modeled with an unconstrained sigmoid function with a variable slope, to allow us to identify the persistent fractions, PF. 2014 Retrovirology Method HIV T332N 32 37 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Furthermore, to allow capture by antibody D7324, substitutions R500K and G507Q were introduced into the C5 region. 2014 Retrovirology Method HIV G507Q;R500K 73;63 78;68 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Neutralization of the sequence-matched BG505.T332N pseudovirus, reported elsewhere for IgG, was performed here with Fabs in the same Tzm-bl assay. 2014 Retrovirology Method HIV T332N 45 50 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. SOS.R6 is fully cleaved, contains the intermolecular SOS bond but lacks the I559P modification; WT.SEKS has the natural REKR cleavage site replaced by the non-scissile motif SEKS, but lacks the SOS and I559P changes; SOS.SEKS has the non-scissile motif, contains the SOS change but lacks I559P; IP.SEKS has the non-scissile motif, contains the I559P change but lacks SOS; SOSIP.SEKS has the non-scissile motif, and contains the SOS and I559P changes. 2014 Retrovirology Method HIV I559P;I559P;I559P;I559P;I559P 76;202;288;344;436 81;207;293;349;441 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The BG505 env gene (BG505.W6M.ENV.C2, GenBank accession numbers ABA61516 and DQ208458) is derived from a neonatal subtype A HIV-1 founder virus. 2014 Retrovirology Method HIV W6M 26 29 Env;Env 10;30 13;33 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The IP.R6 construct that is fully cleaved, contains the I559P change but lacks the intermolecular SOS bond; this construct and WT.R6 were not studied here as their subunits dissociate. 2014 Retrovirology Method HIV I559P 56 61 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The monomeric BG505 gp120 construct was created by introducing a stop codon into the SOSIP.664 gp140 gene at residue 512; the cleavage site was reverted to wild-type (REKR); C501 was reverted to A501; and the L111A substitution was introduced to prevent gp120 dimerization. 2014 Retrovirology Method HIV L111A 209 214 gp120;gp120;gp140 20;254;95 25;259;100 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Although we constructed the single mutation (H221Y) virus as mentioned above to clarify the contribution of H221Y to resistance, the virus was low virus titer. 2014 BMC infectious diseases Method HIV H221Y;H221Y 45;108 50;113 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Amplification of viral genome was performed using a nested PCR procedure, and patient-derived HIV-1 RT fragment carrying K101Q/Y181C/H221 replaced the partner sequence (2843 nt-3485 nt, 643 bp) in pNL4-3 pol to construct the first clone as previously described . 2014 BMC infectious diseases Method HIV K101Q;Y181C 121;127 126;132 Pol;RT 204;100 207;102 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. So we did not obtain a reliable result of single H221Y. 2014 BMC infectious diseases Method HIV H221Y 49 54 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Then, site-directed mutagenesis was carried out to obtain another three HIV-1 clones separately harboring K101Q/Y181C, K101Q/H221Y and K101Q. 2014 BMC infectious diseases Method HIV H221Y;K101Q;K101Q;K101Q;Y181C 125;106;119;135;112 130;111;124;140;117 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. Eight YU2.6248V3 Ala mutants were generated (G306A, V307A, E314A, K315A, V316A, Y317A, F318A and S322A). 2014 PloS one Method HIV E314A;F318A;G306A;K315A;S322A;V307A;V316A;Y317A 59;87;45;66;97;52;73;80 64;92;50;71;102;57;78;85 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. Thus, both the deletion at position 24 and a mutation at position 25 (E322S) were also introduced. 2014 PloS one Method HIV del 24;E322S 15;70 38;75 24909578 Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia. Specifically, mutations on the S108N, N51I, C59R, and I164L positions of the dhfr gene, and A437G, K540E, and A581G positions of the dhps gene were targeted. 2014 Malaria journal Method HIV A437G;A581G;C59R;I164L;K540E;N51I;S108N 92;110;44;54;99;38;31 97;115;48;59;104;42;36 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. Myc-TAK1 K34R, K158R, K209R and Flag-Vpr S79A were generated using PCR-based mutagenesis. 2014 Retrovirology Method HIV K158R;K209R;S79A 15;22;41 20;27;45 Vpr 37 40 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. The pNLENY1-S79A was generated with PCR-based mutagenesis using primers listed in Additional file 1: Table S1. 2014 Retrovirology Method HIV S79A 12 16 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Briefly, 1.106 C8166 cells were transfected using the Amaxa Nucleofector Technology (Lonza, Verviers, Belgium) with 10 microg of the plasmid pNL4.3-DeltaEnv-EGFP, together with 2 microg of isolated PCR product of the envelope of HIV-1, containing the N260Q mutation. 2014 PloS one Method HIV N260Q 251 256 Env 217 225 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. For intracellular staining experiments, 293T cells were seeded in 8-well chamber slides (Ibidi, Beloeil, QC) and transfected with pNL4.3DeltaGagDeltaPol_EGFP WT or N260Q gp120 constructs as described above. 2014 PloS one Method HIV N260Q 164 169 gp120 170 175 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Mutation N260Q, alone or in combination with mutation S128N in gp120 were also introduced in vectors pNL4.3DeltaGagDeltaPol_EGFP and pMQ, using the same strategy as described above. 2014 PloS one Method HIV N260Q;S128N 9;54 14;59 gp120 63 68 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. Briefly, C38V/C280S/L560C p66RT was co-expressed with C38V/C280S p51 RT in bacteria using the pDUET prokaryotic vector. 2014 The Biochemical journal Method HIV C280S;C38V;L560C;C280S;C38V 14;9;20;59;54 19;13;25;64;58 RT 69 71 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. All samples for DEER spectroscopy also contain the D25N mutation and K55C for labeling. 2014 FEBS letters Method HIV D25N;K55C 51;69 55;73 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Buffers were adjusted to pH 9.06 for PRE and POST and pH 9.39 for L63P. 2014 FEBS letters Method HIV L63P 66 70 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Given that the L63P construct contains only one mutation compared to subtype B, assignments were made based upon previously published results. 2014 FEBS letters Method HIV L63P 15 19 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. L63P for NMR studies did not contain the K55C mutation. 2014 FEBS letters Method HIV K55C;L63P 41;0 45;4 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. PRE and POST also contain the C67A and C95A mutations. 2014 FEBS letters Method HIV C67A;C95A 30;39 34;43 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Relaxation measurements were performed on 15N L63P at 600 MHz and 700 MHz as described previously. 2014 FEBS letters Method HIV L63P 46 50 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. The L63P construct was generated using site-directed mutagenesis kit (Strategene) and made within the subtype B background of a pentamutated protease containing the stabilizing mutations Q7K, L33I, L63I and substitution of native cysteines to alanine: C67A, C95A. 2014 FEBS letters Method HIV C67A;C95A;L33I;L63I;L63P;Q7K 252;258;192;198;4;187 256;262;196;202;8;190 PR 141 149 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The gag amplicon was amplified by the primers A1-lower (5' Acry-AGGGGTCGTTGCCAAAGAGTGA-3'; nt 2260-2281) and A1-upper (5'-CACAGGAACAAGCAGCCAGGTC-3') and the amplicons were annealed with the sequencing primer C1548A (5'-AAGGGGAAGTGATATAGCAGGATCTACTAGTA-3'; nt 1482-1513) to detect the T242N mutation or G1562A (5'-TATAGCAGGATCTACTAGTACCCTTCAGGAACAA-3'; nt 1494-1527) to detect the V247I mutation, or G1566C (5'-CAGGATCTACTAGTACCCTTCAGGAACAAGTAG-3'; nt-1499-1531) to detect the G248A mutation. 2014 PloS one Method HIV C1548A;G1562A;G1566C;G248A;T242N;V247I 208;302;399;476;284;380 214;308;405;481;289;385 Gag 4 7 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The tat/env fragment was amplified by using the PCR primers R-lower (5' Acry-GGAAGCACCCAGGAAGTCAGC-3'; nt 5862-5882) and R-upper (5'-GTATCCTCTGATGGGAGGGGCATA-3'; nt 7527-7550), and the amplicons were annealed with the sequencing primer Rev7 (5'-ATGCTACTTACTGCTTTGGTAGAGGCGCTTGATTA-3'; nt 6022-6056) to detect the I64T mutation or the sequencing primer Rev13 (5'-CCTCCTGAGGAATGGTTAAAGACTAT-3'; nt 7299-7324) to detect the R355K mutation. 2014 PloS one Method HIV I64T;R355K 313;421 317;426 Rev;Rev;Tat;Env 236;352;4;8 239;355;7;11 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Analysis of synthetic plasmid mixtures and treatment-naive samples confirmed a detection cut-off of 0.2% for the minor variant of K103N and 0.35% for the Y181C assay. 2014 Journal of virological methods Method HIV K103N;Y181C 130;154 135;159 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. AS-PCR for K103N and Y181C. 2014 Journal of virological methods Method HIV K103N;Y181C 11;21 16;26 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. PCR products were tested for K103N and Y181C by AS-PCR as part of a previously published study. 2014 Journal of virological methods Method HIV K103N;Y181C 29;39 34;44 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Unusual polymorphisms at the 103 position (K103R and K103T) were shown not to compromise the K103N assay, but polymorphisms at the 181 position (Y181F/S) produced false positive results so the one sample with this polymorphism was excluded from analysis. 2014 Journal of virological methods Method HIV K103N;K103R;K103T;Y181F;Y181S 93;43;53;145;145 98;49;58;152;152 25108107 A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF. Expression and purification of MDR769 HIV-1 protease variants (I10V, A82F, A82S and A82T) was performed as described previously. 2014 Journal of molecular graphics & modelling Method HIV A82F;A82S;A82T;I10V 69;75;84;63 73;79;88;67 PR 44 52 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. Amplicons from baseline and virologic failure were tested by an OLA for point mutations conferring resistance to NNRTI (K103N, Y181C and G190A) and 3TC (M184V). 2014 Journal of acquired immune deficiency syndromes (1999) Method HIV G190A;K103N;M184V;Y181C 137;120;153;127 142;125;158;132 NNRTI 113 118 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Sensitivity analysis was performed by including K65R in our definition of multi-NRTI RAMs as this mutation is associated with reduced virological response to tenofovir, didanosine, abacavir and stavudine. 2014 Journal of the International AIDS Society Method HIV K65R 48 52 NRTI 80 84 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Furthermore, the structures of RT with mutations (M184V/I) were also modeled using Discovery Studio 3.1. 2014 PloS one Method HIV M184I;M184V 50;50 57;57 RT 31 33 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Laboratory adaptive strains, including HIV-1IIIB, HIV-1RF, HIV-1 reverse transcriptase (RT) resistant strain, HIV-1LAI-M184V and HIV-1L74V, fusion inhibitor resistant strain pNL4-3gp41 (36G) V38A/N42T, HIV proteaseGene Mutants HIV-1RF/V82F/184V and HIV-1L10R/M46I/L63P/V82T/I84V were kindly donated by NIH. 2014 PloS one Method HIV M46I;M184V 259;119 263;124 RT;RT 65;88 86;90 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The binding mode of compounds FNC and 3TC to RT of wild type and mutant forms (M184V/I) was predicted by the program POSIT of OpenEye (http://www.eyesopen.com/). 2014 PloS one Method HIV M184I;M184V 79;79 86;86 RT 45 47 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. Multidrug resistance was defined as the presence of K65R, Q151M, or at least three TAMs. 2014 PloS one Method HIV K65R;Q151M 52;58 56;63 25174641 Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. Based on our previous surveillance study showing a lack (0%) of significant macrolide-resistant mutations (A2058G or A2059G) among 105 strains of T. 2014 Journal of the International AIDS Society Method HIV A2058G;A2059G 107;117 113;123 25174641 Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. pallidum harbouring an A2058G or A2059G point mutation was investigated using restriction fragment length polymorphism (RFLP). 2014 Journal of the International AIDS Society Method HIV A2058G;A2059G 23;33 29;39 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. The genes for K103N, E138D/K101R and K101R/K103N/E138D RT were cloned into HIV-1LAI. 2014 Nucleic acids research Method HIV E138D;K101R;K103N;E138D;K101R;K103N 49;37;43;21;27;14 54;42;48;26;32;19 RT 55 57 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Briefly, untreated Jurkat cells were infected through spinoculation with NL4-3-IRES-EGFP, NL4-3-IRES-EGFP-IN(R263K), NL4-3-IRES-EGFP-IN(E138K), NL4-3-IRES-EGFP-IN(E138K/R263K), and NL4-3-IRES-EGFP-RT(M184V) cell-free viral particles, using 600 ng p24 per million cells for 2 h at 1200 g, after which cells were washed twice with PBS and cultured for 7 days in the presence of 1 muM DRV to ensure single-round replication. 2014 Viruses Method HIV E138K;E138K;M184V;R263K;R263K 136;163;200;109;169 141;168;205;114;174 p24;IN;IN;IN;RT 247;106;133;160;197 250;108;135;162;199 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Briefly, untreated Jurkat cells were infected through spinoculation with NL4-3-IRES-EGFP, NL4-3-IRES-EGFP-IN(R263K), NL4-3-IRES-EGFP-IN(E138K), NL4-3-IRES-EGFP-IN(E138K/R263K), and NL4-3-IRES-EGFP-RT(M184V) cell-free viral particles, using 600 ng p24 per million cells for 2 h at 1200 g, after which cells were washed twice with PBS and cultured for 72 h. 2014 Viruses Method HIV E138K;E138K;M184V;R263K;R263K 136;163;200;109;169 141;168;205;114;174 p24;IN;IN;IN;RT 247;106;133;160;197 250;108;135;162;199 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Primers used for the generation of pNL4-3-IRES-EGFP-IN(R263K) have been previously reported. 2014 Viruses Method HIV R263K 55 60 IN 52 54 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. The following construct containing a mutation in the reverse transcriptase (RT) gene was created by site directed mutagenesis: pNL4-3-IRES-EGFP-RT(M184V), as described previously. 2014 Viruses Method HIV M184V 147 152 RT;RT;RT 53;76;144 74;78;146 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. The following constructs containing mutations in the integrase gene were created by site-directed mutagenesis: pNL4-3-IRES-EGFP-IN(R263K), pNL4-3-IRES-EGFP-IN(E138K), pNL4-3-IRES-EGFP-IN(E138K/R263K). 2014 Viruses Method HIV E138K;E138K;R263K;R263K 159;187;131;193 164;192;136;198 IN;IN;IN;IN 53;128;156;184 62;130;158;186 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. The following primers were used for mutagenesis: IN E138K: sense: GGCGGGGATCAAGCAGAAATTTGGCATTCCCTA, antisense: TAGGGAATGCCAAATTTCTGCTTGATCCCCGCC. 2014 Viruses Method HIV E138K 52 57 IN 49 51 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. To limit the number of sequences, we first excluded sequences having more than one DRM (other than A62V) and having ambiguous nucleotides at more than 1% of positions. 2014 AIDS (London, England) Method HIV A62V 99 103 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. HeLa-Kb cells transfected with syngag plasmids coding for Gag wt, Gag-SL wt, PTAP-SL, S40F-SL, or S40F/ PTAP-SL were detached and seeded in triplicates into 96 well plates, in concentrations ranging from 50,000 to 150 cells/well. 2014 Viruses Method HIV S40F;S40F 87;99 91;103 Gag;Gag 58;66 61;69 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Introduction of the S40F mutation in the syngag background was achieved by site-directed mutagenesis using the primer pair 5'-ctg tac ccc ctg acc ttc ctg agg agc ctg ttc ggc-3', the S40A mutation by using the primer pair 5'-ctg tac ccc ctg acc gcc ctg agg agc ctg ttc ggc-3', and the Y36A mutation with the primer pair 5'-cga caa gga gct ggc ccc cct gac c-3'. 2014 Viruses Method HIV S40A;S40F;Y36A 182;20;284 186;24;288 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Synthesis and purification of synthetic p6 fragments, p6(23-52)S40F, p6(23-52)S40N and p6(23-52)S40D were performed as described in detail elsewhere. 2014 Viruses Method HIV S40D;S40F;S40N 96;63;78 100;67;82 Gag;Gag;Gag;Gag 40;54;69;87 42;56;71;89 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The crosspeaks observed in the 2D 1H NOESY spectrum of p6(23-52)S40F were assigned and integrated using Sparky NMR Analysis version 3.1.1.4. 2014 Viruses Method HIV S40F 64 68 Gag 55 57 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The MA G2A mutation was introduced by using the primer pair 5'-aga agg aga gag atg gct gcg aga gcg tcg gta-3'. 2014 Viruses Method HIV G2A 7 10 Gag;Matrix 75;4 78;6 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The NL4-3 derived expression constructs pNLenv1 and p R harboring the S40F and PTAP mutations have been previously described, the S40F/ PTAP double mutant has been established analogously. 2014 Viruses Method HIV S40F;S40F 70;131 74;135 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40D mutation was introduced by using the primer pair 5'-act gta tcc ttt agc cga cct cag atc act ctt-3', the S40N mutation using the primer pair 5'-act gta tcc ttt agc caa cct cag atc act ctt-3', and the N-ctrl construct using the primer pair 5'-act gta tcc ttt agc cag cct cag atc act ctt-3'. 2014 Viruses Method HIV S40D;S40N 4;113 8;117 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. 104 293 T or TZM-bl cells infected with pseudotyped G367R virus in a donor coculture were mixed with 5x104 target cells. 2014 Virology journal Method HIV G367R 52 57 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. A defective env G367R mutant virus was produced by transfecting a proviral plasmid, that contained a mutation at position G367R in the CD4 binding site of gp 120, and that has been generated by PCR based site directed mutagenesis. 2014 Virology journal Method HIV G367R;G367R 16;122 21;127 Env 12 15 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Alternatively, 105 MT4 cells infected with pseudotyped G367R virus in a donor coculture were mixed with 2-4x105 MT2 cells. 2014 Virology journal Method HIV G367R 55 60 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. G367R mutant viruses and VSV-G pseudotyped viruses were generated in 293 T cells by transfection from the proviral plasmids with lipofectamine 2000 as recommended by the manufacturer (Invitrogen). 2014 Virology journal Method HIV G367R 0 5 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Based on observed transition points in the trends of M184I/V, emtricitabine and lamivudine, a time lag of 2 years was assumed between the numbers of prescriptions and their effect on M184I/V frequency. 2014 PloS one Method HIV M184I;M184I;M184V;M184V 53;183;53;183 60;190;60;190 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Multiple logistic regression controlling for lamivudine was used to estimate the association between the M184I/V mutation and emtricitabine over the time interval 2005-2011. 2014 PloS one Method HIV M184I;M184V 105;105 112;112 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Thus, the frequency of M184I/V from the years 2005-2011 was hypothesized to be associated with the number of prescriptions of emtricitabine from 2003-2009. 2014 PloS one Method HIV M184I;M184V 23;23 30;30 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. The PS1 primer set produced a 547 bp amplicon that was used to detect M41L, K65R, K70R, and K103N, and the PS2 primer set produced a 512 bp amplicon that was used to detect K103N, M184V, and T215Y/F. 2014 PloS one Method HIV K103N;K103N;K65R;K70R;M184V;M41L;T215F;T215Y 92;173;76;82;180;70;191;191 97;178;80;86;185;74;198;198 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Construction of K103N & Y181C plasmid controls. 2014 PloS one Method HIV K103N;Y181C 16;24 21;29 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Detection and quantification of K103N and Y181C mutants by AS-PCR. 2014 PloS one Method HIV K103N;Y181C 32;42 37;47 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Mutant specific primers refer to primers for the K103N-AAC, K103N-AAT or Y181C-TGT alleles that specifically amplify the mutant sequences. 2014 PloS one Method HIV K103N;K103N;Y181C 49;60;73 54;65;78 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The non-specific primers and mutant specific primers for K103N and Y181C mutants were designed by choosing the maximum consensus sequence from alignments of 598 HIV-1 subtype B and C sequences available from the Los Alamos National Laboratories HIV sequence database (www.hiv.lanl.gov). 2014 PloS one Method HIV K103N;Y181C 57;67 62;72 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The three desired single-mutant plasmids used as standards, K103N-AAC, K103N-AAT, and Y181C-TGT were created using mutagenic primer sequences containing the following substitutions: K103N (AAA AAC, AAA AAT) and Y181C (TAT TGT). 2014 PloS one Method HIV K103N;K103N;K103N;Y181C;Y181C 60;71;182;86;211 65;76;187;91;216 Tat 218 221 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. A total of 224 Xhosa-speaking individuals were enrolled in the study including 174 seropositive individuals (C30C31 motif n = 128, C31S motif n = 46) and 50 seronegative individuals similar in ethnicity, age, language, and education. 2014 Journal of neurovirology Method HIV C31S 131 135 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Nucleotide sequences were translated into amino acid sequences and the C30C31 motif or C31S mutation for each patient was noted. 2014 Journal of neurovirology Method HIV C31S 87 91 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Similar MANCOVA models were fitted to compare HIV positive individuals with and without the C31S defect and to test whether viral factors and immune status significantly predicted each multivariate neuropsychological construct. 2014 Journal of neurovirology Method HIV C31S 92 96 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The final selected complex of wild type was denoted as WT, complex of N43D mutation and C34 was denoted as N43D single mutant, while the complex of N43D mutation and C34 with S138A mutation was denoted as N43D/S138A double mutant. 2014 PloS one Method HIV N43D;N43D;N43D;N43D;S138A;S138A 70;107;148;205;175;210 74;111;152;209;180;215 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The mutations of N43D in receptor and S138A in ligand C34 were constructed by the Biopolymer module in Sybyl, version 7.3 (Sybyl Molecular Modeling Software, Tripos Associates, Inc., St. 2014 PloS one Method HIV N43D;S138A 17;38 21;43 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The subsequent WT, N43D mutant and N43D/S138A mutant complex MD simulations were conducted as the same procedures mentioned above. 2014 PloS one Method HIV N43D;N43D;S138A 19;35;40 23;39;45 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The wild type gp41 5-Helix receptor was denoted as WT, the 5-Helix with N43D mutation was named as N43D. 2014 PloS one Method HIV N43D;N43D 72;99 76;103 gp41 14 18 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. A previously described HTRF-based assay was modified to monitor LEDGF/p75 binding to WT and H171T INs. 2014 Retrovirology Method HIV H171T 92 97 IN 98 101 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. A Superdex 200 10/300 GL column (GE Healthcare) was used to analyze multimeric forms of recombinant WT and H171T INs in buffer containing 20 mM HEPES (pH 6.8), 750 mM NaCl, 10 mM MgSO4, 0.2 mM EDTA, 5 mM BME, 5% glycerol and 200 muM ZnCl2. 2014 Retrovirology Method HIV H171T 107 112 IN 113 116 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Briefly, C-terminally FLAG-tagged LEDGF/p75 (0.01 - 100 nM) was titrated in the binding buffer (25 mM Tris, pH 7.4, 150 mM NaCl, 2 mM MgCl2, 0.1% Nonidet P-40, 1 mg/ml BSA) containing 10 nM N-terminally 6XHis WT or H171T HIV-1 IN. 2014 Retrovirology Method HIV H171T 215 220 IN 227 229 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Briefly, DMSO, 0.12 muM BI-D, or 10 muM BI-D was incubated with 200 nM WT or H171T IN. 2014 Retrovirology Method HIV H171T 77 82 IN 83 85 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. For LEDGF/p75 dependent integration assays, 100 nM WT or H171T IN was incubated with 50 nM Cy-5 labeled donor, 10 nM biotinylated target DNA and 50 nM or 100 nM LEDGF/p75. 2014 Retrovirology Method HIV H171T 57 62 IN 63 65 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. LEDGF/p75 independent assays were executed by incubating 400 nM WT or H171T IN with 50 nM Cy-5 labeled donor DNA and 10 nM biotinylated target DNA. 2014 Retrovirology Method HIV H171T 70 75 IN 76 78 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Recombinant H171T IN CCD (50-212) containing the F185K solubilizing substitution was prepared to ~8 mg/ml and grown at 4 C using hanging drop vapor diffusion method. 2014 Retrovirology Method HIV F185K;H171T 49;12 54;17 IN 18 20 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The H171T substitution was introduced into the IN coding region of pNLX.Luc.R-, pNL4-3.Luc.Env- and pNL4-3/Xmal using PCR-site directed mutagenesis (Agilent) and verified by dideoxy sequencing. 2014 Retrovirology Method HIV H171T 4 9 Env;IN 91;47 94;49 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. WT and H171T HIV-1 IN CCD (residues 50-212) containing the F185K mutation were expressed in E. 2014 Retrovirology Method HIV F185K;H171T 59;7 64;12 IN 19 21 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. WT HIV-1 IN, H171T HIV-1 IN and LEDGF/p75 recombinant proteins with 6xHis or FLAG tags were expressed in E. 2014 Retrovirology Method HIV H171T 13 18 IN;IN 9;25 11;27 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. WT or H171T 6xHis-CCD 4 mug/mL in HBS-P, (GE Healthcare) was immobilized on the chip to 4400 response units (RU). 2014 Retrovirology Method HIV H171T 6 11 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Cells were transduced with 50 vRNAc of vector particles carrying a WT or a D167H IN. 2014 Molecular therapy. Nucleic acids Method HIV D167H 75 80 IN 81 83 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Plasmid p8.91_D64V was a kind gift from DB. 2014 Molecular therapy. Nucleic acids Method HIV D64V 14 18 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Plasmid p8.91_N was described earlier, plasmids p_8.91_LQ, p8.91_Q168A, p8.91_D167H, and p8.91_D64V_D167H were constructed by inserting a SwaI-AflII synthesized DNA fragments (Genescript, Piscataway, NJ) from p8.91 containing a large part of the integrase and including LQ, Q168A, D167H, or D64V and D167H substitutions. 2014 Molecular therapy. Nucleic acids Method HIV D167H;D167H;D167H;D64V;Q168A;D167H;D64V;Q168A 281;300;100;291;274;78;95;65 286;305;105;295;279;83;99;70 IN 246 255 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Ten thousand HEK-293T cells were transduced with vector pTrip PGK-Pac/CMV-Gfp carrying WT or mutants IN (D167H, Q168A, N, or LQ) at MOI of 100, 300, 900, and 2,700 viral RNA copies/cell (vRNAc/cell). 2014 Molecular therapy. Nucleic acids Method HIV D167H;Q168A 105;112 110;117 IN 101 103 25488402 Modulation of HIV protease flexibility by the T80N mutation. MD simulations extending to 100 ns were run on both WT and T80N HIVp structures. 2015 Proteins Method HIV T80N 59 63 25488402 Modulation of HIV protease flexibility by the T80N mutation. Three-dimensional molecular envelopes for HIVp were determined from observed data from HIVp (WT) and HIVp (T80N) and from the WAXS profile calculated on the basis of atomic coordinates (1F7A) using programs from the ATSAS suite for the analysis of solution x-ray scattering data. 2015 Proteins Method HIV T80N 107 111 Env 28 37 25488402 Modulation of HIV protease flexibility by the T80N mutation. WT included a substitution of Q7K to prevent autoproteolysis . 2015 Proteins Method HIV Q7K 30 33 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. In replication competition experiments, DCs were infected with 100 ng p24 of both HIV-WT and HIV-M184T. 2014 Retrovirology Method HIV M184T 97 102 p24 70 73 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The mutation resulting in amino acid change K103N was introduced in HXB2 by site-directed mutagenesis using the previously described vector system with addition of primer K103N (5'-GTTACTGATTTGTTCTTTTTTAACCC-'3). 2014 Retrovirology Method HIV K103N;K103N 44;171 49;176 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The site-directed mutants M184V, M184I and M184T were previously generated in the background of HXB2. 2014 Retrovirology Method HIV M184I;M184T;M184V 33;43;26 38;48;31 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Crystal structures of PRG48T/L89M bound with saquinavir (PRG48T/L89M-SQV) (PDB ID code 4QGI) and HIV PR bound with saquinavir (PRWT-SQV) (PDB code 1HXB) were superimposed on all Calpha atoms using the LSQAB alignment program in the CCP4 software package. 2015 Biochemistry Method HIV L89M;L89M 29;64 33;68 PR;PR;PR 22;57;101 24;59;103 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Data was collected using an RU-H3R rotating Cu anode (lambda = 1.5148 A) operating at 50 kV and 22 mA utilizing an R-Axis IV+2 image plate detector (Rigaku, USA). 2015 Biochemistry Method HIV H3R 31 34 Matrix 99 101 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. For HIV B Gly48Thr/Leu89Met, 50 mug/L of kanamycin was added. 2015 Biochemistry Method HIV G48T;L89M 10;19 18;27 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. For the HIV B Gly48Thr/Leu89Met variant the codon optimized DNA containing the desired mutations was synthesized (DNA 2.0), subcloned in the expression vector, pJExpress, and sequenced by DNA 2.0. 2015 Biochemistry Method HIV G48T;L89M 14;23 22;31 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. HIV B and HIV B Gly48Thr/Leu89Met protease constructs were transformed into the E. 2015 Biochemistry Method HIV G48T;L89M 16;25 24;33 PR 34 42 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The initial coordinates and sequence for PRWT-SQV and PRG48T/L89M-SQV were obtained from the X-ray crystal structures PDB ID code 1HXB and PDB ID code 4QGI, respectively. 2015 Biochemistry Method HIV L89M 61 65 PR 54 56 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The Michaelis-Menten constants kcat, Km, and kcat/Km, as well as the inhibition constant, Ki, were determined for PRWT and PRG48T/L89M, as previously described. 2015 Biochemistry Method HIV L89M 130 134 PR 123 125 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The PRG48T/L89M buffer was exchanged to 50 mM sodium acetate, 1 mM EDTA, and 1 mM DTT, pH 4.7 during concentration to 3.5 mg/mL. 2015 Biochemistry Method HIV L89M 11 15 PR 4 6 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. The W427S mutant was constructed using mutagenesis kit as described previously. 2014 PloS one Method HIV W427S 4 9 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. For Y115F RT, a 24-mer DNA primer (5'-TCAGGTCCCTGTTCGGGCGCCACT) was annealed to a 36-mer DNA template (5'-TCTCTAGCAGTGGCGCCCGAACAGGGACCTGAAAGC), and this P/T pair was used to measure dGTP single nucleotide incorporation. 2015 Antiviral research Method HIV Y115F 4 9 RT 10 12 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. The Y115F mutation was introduced into the p66 subunit using a QuikChange Site-Directed Mutagenesis Kit from Agilent Technologies. 2015 Antiviral research Method HIV Y115F 4 9 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The PDB entries are: 1T3R for the WT, 2HS1 for the V32I mutant and 2HS2 for the M46L mutant structures. 2015 Journal of molecular graphics & modelling Method HIV M46L;V32I 80;51 84;55 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Construction of M36I PR models. 2014 BMC genomics Method HIV M36I 16 20 PR 21 23 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. To obtain the M36I PR structures in complex with each substrate, we carried out comparative modeling using each corresponding WT-PR crystallographic structures complex as a template. 2014 BMC genomics Method HIV M36I 14 18 PR;PR 19;129 21;131 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Baseline patient-derived viral protease genes harboring M46I, M46L, L90M or I54V + V82A + L90M or the N-terminus of RT containing M41L, M41L + T69S + L210E + T215S or K103N were introduced into HXB2 using the same vector system. 2014 Retrovirology Method HIV I54V;K103N;L210E;L90M;L90M;M41L;M41L;M46I;M46L;T215S;T69S;V82A 76;167;150;68;90;130;136;56;62;158;143;83 80;172;155;72;94;134;140;60;66;163;147;87 PR;RT 31;116 39;118 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Mutations M46I, M46L and L90M in protease and M41L, M41L + T215Y and K103N in RT were introduced in HXB2 by site-directed mutagenesis using the previously described vector systems CP-MUT and NRT-MUT and the following primers: M46I 5'-GGA AAC CAA AAA TAA TAG GG-3' (HXB2 nucleotides 2380-2396), M46L 5'-GGA AAC CAA AAC TGA TAG GG-3' (HXB2 nucleotides 2380-2396), L90M 5'-GAA ATC TGA TGA CTC AGA TTG-3' (HXB2 nucleotides 2511-2532), M41L 5'-ATT TGT ACA GAG CTG GAA AAG GAA G-3' (HXB2 nucleotides 2658-2682), K103N 5'-GTT ACT GAT TTG TTC TTT TTT AAC CC-3' (HXB2 nucleotides 2844-2869), T215Y 5'-TGTCTG GTG TGTAAA GTCCCCACC-3' (HXB2 nucleotides 3181-3204). 2014 Retrovirology Method HIV K103N;K103N;L90M;L90M;M41L;M41L;M41L;M46I;M46I;M46L;M46L;T215Y;T215Y 69;506;25;362;46;52;431;10;226;16;294;59;583 74;511;29;366;50;56;435;14;230;20;298;64;588 PR;Gag;RT 33;451;78 41;454;80 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. The RC of either the SDM-viruses or the patient-derived viruses was compared to the RC of control viruses (WT, HIV-M184V, -M184I and -M184T). 2014 Retrovirology Method HIV M184I;M184T;M184V 123;134;115 128;139;120 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Mutations in hDAT at Tyr88 and Tyr470 (tyrosine to phenylalanine, Y88F-hDAT and Y470F-hDAT) are expected to destroy the hydrogen bond only. 2015 Journal of neuroimmune pharmacology Method HIV Y470F;Y88F 80;66 85;70 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Since methionine is nearly isosteric with lysine, substitution at Lys92 (lysine to methionine, K92M-hDAT) should abolish the hydrogen bound with minimal perturbations to the native structure of the transporter. 2015 Journal of neuroimmune pharmacology Method HIV K92M 95 99 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Substitution of tyrosine at 470 with alanine or tryptophan (Y470A-hDAT and Y470W-hDAT) is expected to eliminate both hydrogen bond and cation-pi interactions that is similar to Y470H-hDAT, but with different spatial effects on structural organization of the transporter. 2015 Journal of neuroimmune pharmacology Method HIV Y470A;Y470A;Y470H;Y470W 60;16;177;75 65;44;182;80 PI 142 144 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. We have reported that Y470H-hDAT significantly increased DA efflux compared to WT hDAT. 2015 Journal of neuroimmune pharmacology Method HIV Y470H 22 27 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Wild-type (WT) HIV-1BH10 RT and mutant K103N were obtained as previously described. 2015 Nucleic acids research Method HIV K103N 39 44 RT 25 27 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. A representative set of conformations of all wild-type protease-substrate complexes, p1-p6D30N, p1-p6D30N/N88D, LP1'Fp1-p6D30N/N88D, NC-p1V82A, and AP2VNC-p1V82A, generated from MD simulation trajectories of eleven ns production phase are clustered separately to group the 'redundant' conformations and examine the unique conformers. 2015 Evolutionary applications Method HIV D30N;D30N;D30N;V82A;V82A;N88D;N88D 90;101;122;138;157;106;127 94;105;126;142;161;110;131 PR;NC;Gag;Gag;Gag 55;133;88;99;120 63;135;90;101;122 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. For example, LP1'Fp1-p6D30N denotes a complex of D30N protease variant with the LP1'F mutant of the p1-p6 cleavage site, where LP1'F refers to a Leu-to-Phe mutation at P1' position of the cleavage site. 2015 Evolutionary applications Method HIV D30N;D30N 23;49 27;53 PR;Gag;Gag 54;21;103 62;23;105 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The structures of p1-p6D30N, p1-p6D30N/N88D, LP1'Fp1-p6D30N/N88D, NC-p1V82A, and AP2VNC-p1V82A variants are modeled in silico based on their wild-type structures and simulated by MD simulations. 2015 Evolutionary applications Method HIV D30N;D30N;D30N;V82A;V82A;N88D;N88D 23;34;55;71;90;39;60 27;38;59;75;94;43;64 NC;Gag;Gag;Gag 66;21;32;53 68;23;34;55 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Throughout this article, the wild-type HIV-1 protease (WT), the HIV-1 protease mutants (D30N, D30N/N88D, or V82A), and the cleavage site (LP1'F or AP2V) variants in a protease-substrate complex are designated by a subscript and a superscript to the name of the cleavage site. 2015 Evolutionary applications Method HIV D30N;D30N;N88D;V82A 88;94;99;108 92;98;103;112 PR;PR;PR 45;70;167 53;78;175 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Diffraction data for all crystals were collected at Brookhaven NSLS on beamline X29A. 2015 Journal of medicinal chemistry Method HIV X29A 80 84 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Final clones for the RT (Y181C) and RT (K103N/Y181C) were verified by DNA sequencing. 2015 Journal of medicinal chemistry Method HIV K103N;Y181C;Y181C 40;25;46 45;30;51 RT;RT 21;36 23;38 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. For the RT (K103N/Y181C):1 complexes, crystals were first obtained using cocrystallization then dehydrated using similar methods described previously. 2015 Journal of medicinal chemistry Method HIV K103N;Y181C 12;18 17;23 RT 8 10 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. For the RT (Y181C):1, RT (Y181C):2, and RT (K103N/Y181C):2 complexes, crystal soaking techniques were used to obtain the C2 crystal forms. 2015 Journal of medicinal chemistry Method HIV K103N;Y181C;Y181C;Y181C 44;12;26;50 49;17;31;55 RT;RT;RT 8;22;40 10;24;42 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Initially, the RT (Y181C) and RT (K103N/Y181C) enzymes were cocrystalized with low concentrations of rilpivirine (1-5 muM). 2015 Journal of medicinal chemistry Method HIV K103N;Y181C;Y181C 34;19;40 39;24;45 RT;RT 15;30 17;32 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Recombinant RT (WT), RT (Y181C), and RT (K103N) enzymes were expressed and purified to homogeneity using methods described previously. 2015 Journal of medicinal chemistry Method HIV K103N;Y181C 41;25 46;30 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The first cycle of mutagenesis was used to create the single (Y181C) mutation, and a second cycle of mutagenesis was used to create the double (K103N/Y181C) mutation. 2015 Journal of medicinal chemistry Method HIV K103N;Y181C;Y181C 144;62;150 149;67;155 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The pCR 2.1-topo vector containing the single Y181C p66 insert and K103N/Y181C p66 insert were digested with NdeI and XhoI, then ligated back into the original RT52A vector. 2015 Journal of medicinal chemistry Method HIV K103N;Y181C;Y181C 67;46;73 72;51;78 RT 160 162 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The RT (K103N/Y181C):1 crystals were then dehydrated to reduce solvent content. 2015 Journal of medicinal chemistry Method HIV K103N;Y181C 8;14 13;19 RT 4 6 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. To obtain a standard interpretation across tests, HIV-1 transmitted drug resistance was defined according to the World Health Organization (WHO) 2009 surveillance list, with the addition of T215N (a revertant of T215F/Y omitted from the list) and E138K (a nonpolymorphic rilpivirine-associated mutation). 2015 HIV medicine Method HIV E138K;T215F;T215N;T215Y 247;212;190;212 252;219;195;219 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Selection for flowcytometry evaluations was based on cell availability, presence of A163G mutations in the KF11epitope and/or possession of HLA B*57 or B*5801 alleles. 2015 Vaccine Method HIV A163G 84 89 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Mutagenic oligonucleotide 'RH1' (5'-AAAGAAAAAAAACAGTACTAGATGGAGAAAATTAGTAGATTTCAG-3') was used to introduce the TAMs D67N (GAC- AAC) and K70R (AAA-AGA) in the RT coding region to generate the construct pHIVTAM. 2015 Nucleic acids research Method HIV D67N;K70R 117;137 121;141 RT 159 161 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. pHIVTAM was used as the template to generate pHIVTAMK65K and pHIVTAMK66K containing D67N/K70R and the additional silent mutation at codon 65 (AAA to AAG) and codon 66 (AAA to AAG), using the oligonucleotides 'RH3' (5'-CCAGTATTTGCCATAAAGAAGAAAAACAGTACTAGATGGAG-3') and 'RH2' (5'-AAGAAAAAGAACAGTACTAGATGGAGAAAATTAGTAGATTTCAG-3'), respectively. 2015 Nucleic acids research Method HIV D67N;K70R 84;89 88;93 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. 2D [1H-15N] HSQC experiments were recorded in the absence and presence of ATP (21 mM) (Jena Bioscience, Jena, Germany) with RTshort-WT, RTshort-mt4 and RTshort-mt4-T345S in binding buffer [50 mM Tris/HCl pH 6.725 C, 150 mM NaCl, 6 mM MgCl2, 0.5 mM DTT] with 10% (v/v) D2O at 298 K. 2015 Retrovirology Method HIV T345S 164 169 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. SFVmac RTshort-WT, -mt4 and -mt4-T345S, coding for amino acid residues 107-368 of the PR-RT, were cloned into the vector pET-GB1a (G. 2015 Retrovirology Method HIV T345S 33 38 PR;RT 86;89 88;91 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. T215 mutations other than T215Y/F were called T215 revertants because they often emerge in individuals initially infected with a virus containing T215Y/F. 2015 PLoS medicine Method HIV T215F;T215F;T215Y;T215Y 26;146;26;146 33;153;33;153 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Thymidine-analog mutations (TAMs) were defined as the NRTI SDRMs M41L, D67N/G/E, K70R, L210W, T215Y/F/S/C/D/E/I/V, and K219Q/E/N/R. 2015 PLoS medicine Method HIV D67E;D67G;D67N;K219E;K219N;K219Q;K219R;K70R;L210W;M41L;T215C;T215D;T215E;T215F;T215I;T215S;T215V;T215Y 71;71;71;119;119;119;119;81;87;65;94;94;94;94;94;94;94;94 79;79;79;130;130;130;130;85;92;69;113;113;113;113;113;113;113;113 NRTI 54 58 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. PBMCs were limiting and were unavailable at other time points or from the IVR-tenofovir and vaginal tenofovir gel with SHIVSF162P3-K65R studies. 2015 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R 131 135 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. SHIVSF162P3-K65R virus has 10-fold less infectivity compared to SHIVSF162P3, based on virus infectivity to particle ratio, described in. 2015 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R 12 16 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. SHIVSF162P3-K65R virus has a K65R mutation in the reverse transcriptase enzyme, rendering the virus partially resistant to tenofovir. 2015 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R;K65R 29;12 33;16 RT 50 71 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. The vaginal tenofovir gel study with SHIVSF162P3-K65R virus included six pigtail macaques in the PrEP-treated and six in the control arms. 2015 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R 49 53 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. Vaginal tenofovir gel (1%, delivering 30 mg tenofovir in a 3 mL volume) or a placebo gel were administered to the animals 30 minutes prior to vaginal virus challenges at an adjusted dose of 500 TCID50 SHIVSF162P3-K65R to compensate for lower infectivity, twice weekly for up to 20 challenges. 2015 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R 213 217 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. For any patients with the M184V/I RAM present at screening, emtricitabine or lamivudine could be included as a third (not fully active) N[t]RTI for the purpose of maintaining M184V/I. 2014 AIDS research and therapy Method HIV M184I;M184I;M184V;M184V 26;175;26;175 33;182;33;182 NRTI 136 143 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. Patients were required to have plasma VL >=1000 HIV-1 RNA copies/ml (Amplicor HIV-1 Monitor Test, version 1.5, Roche Diagnostics, Basel, Switzerland) at screening, eGFRCG >=80 ml/min, genotypic sensitivity to the two investigator-selected N[t]RTIs (GenoSure MG assay, Monogram Biosciences, South San Francisco, CA, USA), and none of the following darunavir RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V or L89V. 2014 AIDS research and therapy Method HIV I47V;I50V;I54L;I54M;I84V;L33F;L76V;L89V;T74P;V11I;V32I 382;388;400;394;418;376;412;426;406;364;370 386;392;404;398;422;380;416;430;410;368;374 NRTI;Capsid 239;312 247;314 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Activated PBMCs (3 x 106 cells) were infected by spinoculation with HIV or HIV M184V at 105 relative luciferase units. 2015 Molecules (Basel, Switzerland) Method HIV M184V 79 84 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. GHOST cells were infected with 15 ng of p24 antigen of HIV or HIV M184V in the presence of increasing concentrations of emetine, during an adsorption period of 16 h at 37 C/5% CO2. 2015 Molecules (Basel, Switzerland) Method HIV M184V 66 71 p24 40 43 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. HIV-1 virus stocks were produced in HEK-293T cells by transfection using FuGENE HD (Promega) with pNL4-3-Luc (HIV) or pNL4-3-Luc M184V (HIV-M184V), following the recommendations of the manufacturer. 2015 Molecules (Basel, Switzerland) Method HIV M184V;M184V 140;129 145;134 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. The NRTI-resistant mutation M184V was introduced in the RT gene of HIV luciferase proviral clone by the QuikChange Site-Directed Mutagenesis kit (Strategene). 2015 Molecules (Basel, Switzerland) Method HIV M184V 28 33 NRTI;RT 4;56 8;58 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. A NVP RAM was considered if at least one of the following genetic changes in reverse transcriptase was detected: A98G, K101E, K101H, K101P, K103N, V106A, V106M, V108I, Y181C, Y181V, Y188L and G190A. 2015 PloS one Method HIV A98G;G190A;K101E;K101H;K101P;K103N;V106A;V106M;V108I;Y181C;Y181V;Y188L 113;192;119;126;133;140;147;154;161;168;175;182 117;197;124;131;138;145;152;159;166;173;180;187 RT 77 98 26241860 The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon. Distribution of the natural Y181C mutation. 2015 PLoS pathogens Method HIV Y181C 28 33 26241860 The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon. To investigate the distribution of the natural 181C resistance mutation, we used the sequences from the 100 NNRTI-naive patients and studied the association between clade and Y181C residue by using a chi-squared test. 2015 PLoS pathogens Method HIV Y181C 175 180 NNRTI 108 113 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. The K65R substitution in SHIV162P3 confers ~5-fold reduction in susceptibility to TFV and was introduced by site-directed mutagenesis with two nucleotide changes (AAA CGA) to minimize reversion of K65R in vivo. 2015 Retrovirology Method HIV K65R;K65R 4;199 8;203 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Dolutegravir resistance categories were as follows: (i) no resistance, absence of Q148H/R/K; (ii) low-level resistance, Q148H/R/K in the absence of G140S/A/C, L74I and E138A/K/T; (iii) intermediate-level resistance, Q148H/R/K with one of the mutations G140S/A/C, L74I or E138A/K/T; and (iv) high-level resistance, Q148H/R/K with two or three of the mutations G140S/A/C, L74I and E138A/K/T. 2015 The Journal of antimicrobial chemotherapy Method HIV E138A;E138A;E138A;E138K;E138K;E138K;E138T;E138T;E138T;G140A;G140A;G140A;G140C;G140C;G140C;G140S;G140S;G140S;L74I;L74I;L74I;Q148H;Q148H;Q148H;Q148H;Q148K;Q148K;Q148K;Q148K;Q148R;Q148R;Q148R;Q148R 168;271;379;168;271;379;168;271;379;148;252;359;148;252;359;148;252;359;159;263;370;82;120;216;314;82;120;216;314;82;120;216;314 177;280;388;177;280;388;177;280;388;157;261;368;157;261;368;157;261;368;163;267;374;91;129;225;323;91;129;225;323;91;129;225;323 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Major RAMs comprised T66A/I/K, E92Q/G/V, F121Y, G140S/A/C, Y143H/R/C/K, S147G, Q148H/R/K and N155H/S/T. 2015 The Journal of antimicrobial chemotherapy Method HIV E92G;E92Q;E92V;F121Y;G140A;G140C;G140S;N155H;N155S;N155T;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;Y143C;Y143H;Y143K;Y143R 31;31;31;41;48;48;48;93;93;93;79;79;79;72;21;21;21;59;59;59;59 39;39;39;46;57;57;57;102;102;102;88;88;88;77;29;29;29;70;70;70;70 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. According to the specificity of the primers, T215F primer cross reacted with T215L/I/ L/V, and T215Y primer with T215D/N /Y (S1 Table). 2015 PloS one Method HIV T215D;T215F;T215I;T215L;T215V;T215N;T215Y 113;45;77;77;77;113;95 120;50;89;89;89;120;100 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Briefly, mutation-specific primers were designed for seven reverse transcriptase inhibitor resistance mutations, M41L, K65R, K70R, K103N, Y181C, M184V, and T215F/Y (S1 Table). 2015 PloS one Method HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y;Y181C 131;119;125;145;113;156;156;138 136;123;129;150;117;163;163;143 RT 59 80 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. The T215I-positive amplicons were similarly analyzed with amplicons spanning codon 215 to 101. 2015 PloS one Method HIV T215I 4 9 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. To avoid possible bias by K103N and T215I mutation in the phylogenetic analysis, K103N and T215I codon positions were removed from the sequences before analysis. 2015 PloS one Method HIV K103N;K103N;T215I;T215I 26;81;36;91 31;86;41;96 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. To evaluate the genetic relationship between minority-level K103N variants detected by AS-PCR and those detected by bulk sequencing, amplicons from AS-PCR reactions that yielded positive results were sequenced and phylogenetic trees were constructed. 2015 PloS one Method HIV K103N 60 65 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. To increase the genetic sequence information for phylogenetic analyses, we extended the K103N-specific amplicon to the 181-184.REV reverse primer, which allowed amplification of RT codons 103 to 220 (336 bp) (S1 Table). 2015 PloS one Method HIV K103N 88 93 Rev;RT 127;178 130;180 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Plasmid DNA encoding PR (subtype B of group M) with 20 mutations Q7K; L10F; I13V; I15V; D30N; V32I; L33F; E35D; M36I; S37N; I47V; I54L; Q58E; I62V; L63P; A71V; I84V; N88D; L89T and L90M (termed PR20) cloned between the Nde1 and BamH1 sites of pET11a vector (Novagen; San Diego; CA) was used to introduce the D25N mutation by the Quick-Change mutagenesis kit (Stratagene). 2015 Journal of molecular graphics & modelling Method HIV A71V;D25N;D30N;E35D;I13V;I15V;I47V;I54L;I62V;I84V;L10F;L33F;L63P;L89T;L90M;M36I;N88D;Q58E;Q7K;S37N;V32I 154;308;88;106;76;82;124;130;142;160;70;100;148;172;181;112;166;136;65;118;94 158;312;92;110;80;86;128;134;146;164;74;104;152;176;185;116;170;140;68;122;98 Capsid;PR;PR 278;21;194 280;23;196 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Preparation of PR20 with D25N mutation. 2015 Journal of molecular graphics & modelling Method HIV D25N 25 29 PR 15 17 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. By analysing five samples of recombinant wild-type virus NL4.3 with viral loads ranging from 103 to 109 copies/ml, we found the highest error rate for unknown drug resistance mutations detected in our sample panel to be 0.25% for E138K. 2015 PloS one Method HIV E138K 230 235 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. HIV-1 subtype A-, D-, and C-specific ASPCR was established for seven resistance-associated key mutations selected by AZT (K70R, T215Y/F), 3TC (M184V), and NVP (K103N, Y181C) with detection limits below 1% as described by Hauser et al. 2015 PloS one Method HIV K103N;K70R;M184V;T215F;T215Y;Y181C 160;122;143;128;128;167 165;126;148;135;135;172 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. M19921) and a mutant pNL4.3 derived clone that harbours seven resistance mutations in the RT (M41L, A62V, A98G, K103N, V118I, L210W, T215Y). 2015 PloS one Method HIV A62V;A98G;K103N;L210W;M41L;T215Y;V118I 100;106;112;126;94;133;119 104;110;117;131;98;138;124 RT 90 92 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. The lowest proportion quantified was 0.32% T215Y in the 0.5% mixture. 2015 PloS one Method HIV T215Y 43 48 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. To compare directly UDS and ASPCR for six known key resistance mutations analysed by ASPCR (K70R, K103N, Y181C, M184V, T215Y/F), we also permitted a cut-off of less than 1% if at least 10 mutant reads balanced between the forward and reverse directions were present. 2015 PloS one Method HIV K103N;K70R;M184V;T215F;T215Y;Y181C 98;92;112;119;119;105 103;96;117;126;126;110 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. Samples positive for the K65R mutation were retested by allele-specific PCR (ASP). 2014 Journal of AIDS & clinical research Method HIV K65R 25 29 Asp 77 80 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. The primers for K65R ASP were, K65wt 5'-CTCCARTATTTGCCATAAAACA-3', K65R 5'-CTCCARTATTTGCCATAAAACG-3' and K65REV 5' TATTCCTAATTGAACYTCCCA-3'. 2014 Journal of AIDS & clinical research Method HIV K65E;K65R;K65R;K65R;K65V 105;105;16;67;105 111;111;20;71;111 Asp 21 24 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Site-directed mutagenesis was carried out to reverse H221Y and/or Y181C of pMD-18 T, which harbored T215Y/V179E/Y181C/H221Y and T215Y/K103N/Y181C/H221Y, respectively. 2015 Virology journal Method HIV H221Y;H221Y;K103N;T215Y;T215Y;V179E;Y181C;Y181C;H221Y;Y181C 118;146;134;100;128;106;112;140;53;66 123;151;139;105;133;111;117;145;58;71 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. The following mutations were introduced into RT of recombinant pNL4-3 plasmids: T215Y/V179E/Y181C/H221Y, T215Y/V179E/Y181C, T215Y/V179E/H221Y, T215Y/V179E, T215Y/K103N/Y181C/H221Y, T215Y/K103N/Y181C, T215Y/K103N/H221Y, and T215Y/K103N. 2015 Virology journal Method HIV H221Y;H221Y;H221Y;H221Y;K103N;K103N;K103N;T215Y;T215Y;T215Y;T215Y;T215Y;T215Y;V179E;V179E;V179E;Y181C;Y181C;Y181C;Y181C;K103N;T215Y;T215Y;V179E 98;136;174;212;162;187;206;80;105;124;156;181;200;86;111;130;92;117;168;193;229;143;223;149 103;141;179;217;167;192;211;85;110;129;161;186;205;91;116;135;97;122;173;198;234;148;228;154 RT 45 47 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. We used quantitative data hypothesis testing in a factorial design to analyze the role of H221Y and the interactions between 181 and 221. 2015 Virology journal Method HIV H221Y 90 95 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. Assessment of the M184V mutation and NNRTI resistance were selected prior to data analysis. 2016 Tropical medicine & international health Method HIV M184V 18 23 NNRTI 37 42 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. The M184V mutation was selected because its presence suggests continued selective pressure from partial or complete ART adherence. 2016 Tropical medicine & international health Method HIV M184V 4 9 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. We included presence of either the M184V mutation or any NNRTI resistance and HIV RNA level as fixed effects and cohort as a random effect. 2016 Tropical medicine & international health Method HIV M184V 35 40 NNRTI 57 62 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. The ENV pseudotyped genes of BG505.T332N, KNH1144 and B41 were kindly provided by Dr. 2015 Bioorganic & medicinal chemistry Method HIV T332N 35 40 Env 4 7 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. A stock of HIV-1NL4.3 and the same strain with a mutated RT gene, HIV-1 NL4.3-pol-W252A, were generated by transfection into HEK293T cells of the corresponding proviral DNA using Lipofectamine 2000 (Invitrogen, Carlsbad, CA) according to the manufacturer's recommendations. 2015 PLoS pathogens Method HIV W252A 82 87 Pol;Capsid;RT 78;221;57 81;223;59 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Briefly, TZM-bl cells were incubated with HIV-1NL4.3 or HIV-1NL4.3-pol-W252A (equivalent to 500 ng CA) at 4 C for 2 h to allow virus attachment. 2015 PLoS pathogens Method HIV W252A 71 76 Pol;Capsid 67;99 70;101 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. HEK293T were treated with 0.8 nM Did B or same volume of DMSO for 2 h at 37 C and then incubated with same amount (equivalent to Cap24), DNAseI treated VSV-G pseudotyped HIV-1NL4.3 or HIV-1 NL4.3-pol-W252A stock for 2 h at 4 C with polybrene (80 mug/mL) and then incubated at 37 C for 4 h. 2015 PLoS pathogens Method HIV W252A 200 205 Pol;Capsid 196;129 199;131 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Mutagenesis of W252A and T253A was undertaken in silico with the individual p51 and p66 subunits, and the p51/p66 heterodimer, independently. 2015 PLoS pathogens Method HIV T253A;W252A 25;15 30;20 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. An HIV-2 protease coding sequence identical to the wild-type, yet harboring the I54M and L90M mutations (A162G, C268A) was synthesized and ligated into pET11a expression plasmid utilizing GenScript services (GenScript USA Inc., Piscataway, NJ, USA). 2015 Viruses Method HIV A162G;C268A;I54M;L90M 105;112;80;89 110;117;84;93 PR 9 17 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Evidence of transmitted HIV-1 drug resistance (TDR) was defined by the presence of at least one surveillance drug resistance mutation (SDRM) from the consensus genotypic definition of Bennett et al., including major RVP-RAMs L100I+K103N, Y181C/I/V, Y188L, and M230L, and minor RPV-RAMs L100I, K103S, V106A, V179F, and G190A/E/S. 2016 AIDS research and human retroviruses Method HIV G190A;G190E;G190S;K103N;K103S;L100I;L100I;M230L;V106A;V179F;Y181C;Y181I;Y181V;Y188L 318;318;318;231;293;225;286;260;300;307;238;238;238;249 327;327;327;236;298;230;291;265;305;312;247;247;247;254 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. In addition, we defined a list of minor RPV-RAMs that have been observed in in vitro or in vivo selection studies and are included in one or more of clinically widely used genotypic resistance interpretation algorithms ANRS (V24), Rega (V9.1.0), and HIVdb (V7.0.1), encompassing V90I, A98G, L100I/V, K101H/Q/T, K103R/S, V106A/I, V108I, E138S, V179D/E/F/I/T, Y181F/G/S, Y188F, V189I, G190A/C/E/Q/S/T/V, and M230V. 2016 AIDS research and human retroviruses Method HIV A98G;E138S;G190A;G190C;G190E;G190Q;G190S;G190T;G190V;K101H;K101Q;K101T;K103R;K103S;L100I;L100V;M230V;V106A;V106I;V108I;V179D;V179E;V179F;V179I;V179T;V189I;V90I;Y181F;Y181G;Y181S;Y188F 285;336;383;383;383;383;383;383;383;300;300;300;311;311;291;291;406;320;320;329;343;343;343;343;343;376;279;358;358;358;369 289;341;400;400;400;400;400;400;400;309;309;309;318;318;298;298;411;327;327;334;356;356;356;356;356;381;283;367;367;367;374 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Major RPV resistance-associated mutations (RPV-RAMs) were defined based on data from the clinical trials, phenotypic RPV resistance analyses, and package inserts: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, M230I/L, and the mutational combination of L100I+K103N. 2016 AIDS research and human retroviruses Method HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;K103N;L100I;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 172;172;172;172;172;219;212;163;163;275;269;226;226;187;194;194;194;205 185;185;185;185;185;224;217;170;170;280;274;233;233;192;203;203;203;210 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Second, to evaluate the reproducibility of a monophyletic cluster of sequences containing E138A, 20 maximum likelihood trees with each including 200 sequences randomly selected from this large dataset were constructed using PhyML. 2016 AIDS research and human retroviruses Method HIV E138A 90 95 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. The origin of E138A in subtype C-infected treatment-naive patients was further investigated by phylogenetic analysis and transmission ratio calculation. 2016 AIDS research and human retroviruses Method HIV E138A 14 19 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. The transmission ratio of E138A was calculated by dividing its prevalence in treatment-naive patients by the prevalence in treatment-experienced patients and interpreted following Winand et al. 2016 AIDS research and human retroviruses Method HIV E138A 26 31 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. For the RT and protease, different mutations at the same position (e.g., M184V and M184I) were treated as separate DRMs despite the fact that some POC assays may be designed to detect multiple amino acids at the same position. 2015 PloS one Method HIV M184I;M184V 83;73 88;78 PR;RT 15;8 23;10 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Generation of the escape neurovirulent clone SIV/17E-Fr K165R. 2016 Journal of neurovirology Method HIV K165R 56 61 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Primary macaque cells (lymphocytes, macrophages, and microglia) and CEMx174 cells were infected in duplicate with either SIV/17E-Fr alone (MOI=0.05), SIV/17E-Fr K165R alone (MOI=0.05), or a 50:50 mixture of wildtype SIV/17E-Fr (MOI=0.025) and SIV/17E-Fr K165R (MOI=0.025) in 6 well plates or 25-cm2 flasks. 2016 Journal of neurovirology Method HIV K165R;K165R 161;254 166;259 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Six macaques were intravenously inoculated with either SIV/17E-Fr or SIV/17E-Fr K165R (groups 1 and 2, Table 1) at a dose of AID50 10,000. 2016 Journal of neurovirology Method HIV K165R 80 85 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. We constructed an infectious SIV molecular clone containing the K165R escape mutation by designing synthetic oligonucleotides with an A to G point mutation to modify the KP9 segment of Gag in the SIV/17E-Fr plasmid to K165R using the QuikChange Site-directed Mutagenesis kit (Stratagene, Agilent Technologies ). 2016 Journal of neurovirology Method HIV K165R;K165R 64;218 69;223 Gag 185 188 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. The selected specimens included HIV subtypes A (N = 8), C (N = 1), D (N = 5), AE (N = 9) and G (N = 3), and one or more drug resistance mutations at four codons in HIV reverse transcriptase (K103N, Y181C, G190A and M184V) spanning a wide range of frequencies in each subjects' HIV population. 2016 PloS one Method HIV G190A;K103N;M184V;Y181C 205;191;215;198 210;196;220;203 RT 168 189 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. Two mul of diluted DNA were added to 20mul reaction mixture containing: 0.67U of thermostable Ampligase ligase (Epicentre Technology, A3210K, Madison, WI), 12.5mM KCl, 1mM NAD (Sigma, 7004, St. 2016 PloS one Method HIV A3210K 134 140 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Briefly, in 100 muL reaction volume containing 50 mM Tris-HCl buffer pH 7.8, 6 mM MgCl2, 1 mM DTT, 80 mM KCl, fix amount of enzymes according to a linear range of dose-response curve: 20 ng of WT RT; 37.5 ng V106A RT; 75 ng V108A RT; 100 ng E224A RT; 100 RT ng A502F RT; 37.5 ng A508V RT, and increasing concentrations (from 0 to 500 nM) of hybrid RNA/DNA 5'-GAUCUGAGCCUGGGAGCU-Fluorescin-3'/ 5'-Dabcyl-AGCTCCCAGGCTCAGATC-3'. 2016 PloS one Method HIV A502F;A508V;E224A;V106A;V108A 261;279;241;208;224 266;284;246;213;229 RT;RT;RT;RT;RT;RT;RT 196;214;230;247;255;267;285 198;216;232;249;257;269;287 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. HIV RT-associated RNase H activity was measured as described in 100 muL reaction volume containing 50 mM Tris-HCl buffer pH 7.8, 6 mM MgCl2, 1 mM dithiothreitol (DTT), 80 mM KCl, 0.25 muM hybrid RNA/DNA 5'-GAUCUGAGCCUGGGAGCU-Fluorescin-3' (HPLC, dry, QC: Mass Check) (available from Metabion) 5'-Dabcyl-AGCTCCCAGGCTCAGATC-3'(HPLC, dry, QC: Mass Check), increasing concentrations of inhibitors, whose dilution were made in water, and different amount of enzymes according to a linear range of dose-response curve: 20 ng of WT RT; 60 ng K103N RT; 37.5 ng V106A RT; 75 ng V108A RT; 5 ng Y181C RT; 50 ng Y188A RT; 30 ng Y188L RT; 100 ng E224A RT; 37.5 ng P225A RT; 20 ng P226A RT; 18 ng F227A RT; 30 ng L228A RT; 30 ng W229A RT; 10 ng M230A RT; 30 ng G231A RT; 62.5 ng N474A RT; 1 mug Y501A RT; 100 ng A502F RT; 37.5 ng A508V RT; 38 ng HIV-1 group O RT. 2016 PloS one Method HIV A502F;A508V;E224A;F227A;G231A;K103N;L228A;M230A;N474A;P225A;P226A;V106A;V108A;W229A;Y181C;Y188A;Y188L;Y501A 798;816;633;683;747;535;699;731;765;651;667;553;569;715;584;600;616;781 803;821;638;688;752;540;704;736;770;656;672;558;574;720;589;605;621;786 RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT 4;525;541;559;575;590;606;622;639;657;673;689;705;721;737;753;771;787;804;822;846 6;527;543;561;577;592;608;624;641;659;675;691;707;723;739;755;773;789;806;824;848 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. RNA-dependent DNA polymerase (RDDP) activity was measured as described in 25 muL volume containing 60 mM Tris-HCl buffer pH 8.1, 8 mM MgCl2, 60 mM KCl, 13 mM DTT, 2.5 muM poly(A)-oligo(dT), 100 muM dTTP, increasing concentrations of inhibitors, whose dilution were made in water, and different amounts of enzymes according to a linear range of dose-response curve: 6 ng wt RT; 30 ng K103N RT; 12 ng V106ART; 19 ng V108A RT; 1.51.5 ng Y181C RT; 45 ng Y188A RT; 15 ng Y188L RT; 30 ng E224A RT; 15 ng P225A RT; 18 ng P226A RT; 23 ng F227A RT; 15 ng L228A RT; 30 ng W229A RT; 30 ng M230A RT; 15 ng G231A RT; 15 ng N474A RT; 15 ng Y501A RT; 15 ng A502F RT; 19 ng A508V RT; 38 ng HIV-1 group O RT. 2016 PloS one Method HIV A502F;A508V;E224A;F227A;G231A;K103N;L228A;M230A;N474A;P225A;P226A;V106A;V108A;W229A;Y181C;Y188A;Y188L;Y501A 642;658;482;530;594;383;546;578;610;498;514;399;414;562;434;450;466;626 647;663;487;535;599;388;551;583;615;503;519;406;419;567;439;455;471;631 Pol;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT;RT 18;373;389;420;440;456;472;488;504;520;536;552;568;584;600;616;632;648;664;688 28;375;391;422;442;458;474;490;506;522;538;554;570;586;602;618;634;650;666;690 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. This region was selected to cover 14 mutations (K103N, V106A/M, V108I, Q151M, Y181C/I, M184V/I, Y188C/L/H, and G190S/A) contributing to NRTI and/or NNRTI resistance. 2016 PloS one Method HIV G190A;G190S;K103N;M184I;M184V;Q151M;V106A;V106M;V108I;Y181C;Y181I;Y188C;Y188H;Y188L 111;111;48;87;87;71;55;55;64;78;78;96;96;96 118;118;53;94;94;76;62;62;69;85;85;105;105;105 NNRTI;NRTI 148;136 153;140 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the RT gene. 2016 The Lancet. Infectious diseases Method HIV K65N;K65R;K70E;K70G;K70Q 69;69;79;79;79 75;75;87;87;87 RT 105 107 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Our secondary outcomes were resistance to first generation NNRTI (efavirenz and nevirapine), defined as specific mutations at aminoacid positions 100, 103, 106, 108, 181, 188, 190, and 225, and cytosine analogue resistance, defined as presence of M184V/I. 2016 The Lancet. Infectious diseases Method HIV M184I;M184V 247;247 254;254 NNRTI 59 64 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. Mutagenesis was performed to obtain an inactive D25N PR mutant. 2016 Frontiers in microbiology Method HIV D25N 48 52 PR 53 55 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. M46I, I54V, V82A, M46I\N88S, G48V\I54V, M46I\V82T\I84V, and G48V\I54V\V82A mutations were introduced into the PR coding region, and K103N, Y181C, K103N\Y181C, K101Q, K101Q\Y181C, K101Q\H221Y, K101Q\H221Y\Y181C, V179E\T215Y, V179E\Y181C\T215Y, V179E\H221Y\T215Y, V179E\Y181C\H221Y\T215Y, K103N\Y181C\T215Y, K103N\H221Y\T215Y, K103N\H221Y\Y181C\T215Y, and M41L\L210W\T215Y\K103N\K238T mutations were introduced into the RT coding region. 2016 PloS one Method HIV G48V;G48V;H221Y;H221Y;H221Y;H221Y;H221Y;H221Y;I54V;I54V;I54V;I84V;K101Q;K101Q;K101Q;K101Q;K103N;K103N;K103N;K103N;K103N;K103N;K238T;L210W;M41L;M46I;M46I;N88S;T215Y;T215Y;T215Y;T215Y;T215Y;T215Y;T215Y;T215Y;V179E;V179E;V179E;V179E;V82A;V82A;V82T;Y181C;Y181C;Y181C;Y181C;Y181C;Y181C;Y181C;Y181C;M46I 29;60;185;198;249;274;312;331;34;65;6;50;166;179;192;159;146;287;306;325;371;132;377;359;354;18;40;23;217;236;255;280;299;318;343;365;211;224;243;262;70;12;45;152;172;204;230;268;293;337;139;0 33;64;190;203;254;279;317;336;38;69;10;54;171;184;197;164;151;292;311;330;376;137;382;364;358;22;44;27;222;241;260;285;304;323;348;370;216;229;248;267;74;16;49;157;177;209;235;273;298;342;144;4 PR;RT 110;418 112;420 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. BirA substrate peptide (BSP)-tagged forms of the A*24:02 heavy chain and beta2 microglobulin (beta2m) were expressed, refolded with peptides (Nef134-10 [RYPLTFGWCF], Nef134-10(Y135F) [RFPLTFGWCF], Nef134-8 [RYPLTFGW], Nef134-8(Y135F) [RFPLTFGW]) (Sigma-Genosys) and purified as described. 2016 PloS one Method HIV Y135F;Y135F 176;227 181;232 Nef;Nef;Nef;Nef 142;166;197;218 145;169;200;221 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. CTL clones T26-102, dually specific for Nef134-8(Y135) and Nef134-8(Y135F), and C1-28, dually specific for Nef134-10(Y135) and Nef134-10(Y135F), were previously established from A*24:02-positive HIV-1-infected individuals. 2016 PloS one Method HIV Y135F;Y135F 68;137 73;142 Nef;Nef;Nef;Nef 40;59;107;127 43;62;110;130 HIV infections 195 209 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Minigene Nef expression vectors pmNef-hRluc-EGFP and pmNef(Y135F)-hRluc-EGFP encoded SF2 Nef codons 123-153 (with or without Y135F, respectively) fused to the N-terminus of Renilla Luciferase. 2016 PloS one Method HIV Y135F;Y135F 59;125 64;130 Nef;Nef 9;89 12;92 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Their specificity and cross-reactivity were verified by dual-tetramer staining with Tet-8(Y135)-APC and Tet-8(Y135F)-PE for T26-102, or Tet-10(Y135)-APC and Tet-10(Y135F)-PE for C1-28. 2016 PloS one Method HIV Y135F;Y135F 110;164 115;169 26977119 A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients. Genetic variants of the IL4, IL13, IL4R, IL13RA1, and IL13RA2 were selected due to evidence of association with and functional significance in the TH2-related condition asthma (IL4-589, rs2243250; IL13-1112, rs1800925; IL4R I50V, rs1805010; IL13RA1, rs2495636) and tissue pathology (IL13RA2, rs5946040). 2016 Mediators of inflammation Method HIV I50V 224 228 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Pseudovirion particles were produced by transfection of human embryonic kidney (HEK) 293T cells with the DeltaEnv HIV-1 genome vector containing either the WT or E45A CA mutant sequence, using a method previously described. 2016 Retrovirology Method HIV E45A 162 166 Capsid 167 169 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Purified recombinant WT and mutant HIV-1 capsid proteins (E45A, E45A/R132T, A204C and A14C/E45C) were restored from lyophilized form by resuspension in storage buffer (20 mM Tris-HCl at pH 8.0, 40 mM NaCl, 60 mM beta-mercaptoethanol) to a final concentration of 160 muM and self-assembled using a method previously described. 2016 Retrovirology Method HIV A14C;A204C;E45A;E45A;E45C;R132T 86;76;58;64;91;69 90;81;62;68;95;74 Capsid 41 47 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Additionally, a suitable R1 side chain oriented toward the interface between the HIV-1 RT p66 and p51 subdomains could overcome the drug resistance of E138 K. 2016 Journal of medicinal chemistry Method HIV E138K 151 157 RT 87 89 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Hetero atoms, such as O or N, in certain R1 substituents could provide additional interactions with the amino acids on interfaces between p66 and p51 subdomains of the RT enzyme via H-bonds or other forces to increase potency against the E138K mutation and improve molecular physicochemical properties, as well as related druglike properties. 2016 Journal of medicinal chemistry Method HIV E138K 238 243 RT 168 170 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. The crystal structures of wild-type and E138K mutant HIV-1 RT in complex with 1b (PDB entry 3MEC) and nevirapine (PDB entry 2HNY), respectively, were downloaded from the RCSB Protein Data Bank for use in this modeling study. 2016 Journal of medicinal chemistry Method HIV E138K 40 45 RT 59 61 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. These limited structural optimizations should provide a better understanding of how structure affects potency against HIV-1 wild-type and resistant viral strains, especially for the E138K mutation, as well as other drug properties, with the aim of discovering and developing potential new NNRTI drug candidates. 2016 Journal of medicinal chemistry Method HIV E138K 182 187 NNRTI 289 294 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Thus, modification of this R1 group could provide an interaction between it and the mutated K138, or other preserved amino acid(s) nearby or on the interface between p66 and p51 subdomains, to possibly overcome mutated E138K resistance. 2016 Journal of medicinal chemistry Method HIV E138K 219 224 27075671 Resolution of Specific Nucleotide Mismatches by Wild-Type and AZT-Resistant Reverse Transcriptases during HIV-1 Replication. To construct an AZTR RT-containing version of pCMVDeltaR8.2, the following amino acid substitutions that confer resistance to AZT: D67N, K70R, T215F, and K219Q were introduced into an HIV reverse transcriptase (RT) gene fragment using overlap extension PCR, sequenced, and used to replace wild-type sequences between AgeI and BclI in pCMVDeltaR8.2 to produce pCBN103-18, which contains an AZT-resistant (AZTR) RT gene. 2016 Journal of molecular biology Method HIV D67N;K219Q;K70R;T215F 131;154;137;143 135;159;141;148 RT;RT;RT;RT 188;21;211;410 209;23;213;412 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. Plasmid isolation and construction of plasmid containing M184V mutation. 2016 PloS one Method HIV M184V 57 62 27107820 HIV-1 capsid is involved in post-nuclear entry steps. C-terminally His-tagged HIV-1 CA A14C/E45C/W184A/M185A quadruple mutant was expressed in E. 2016 Retrovirology Method HIV A14C;E45C;M185A;W184A 33;38;49;43 37;42;54;48 Capsid 30 32 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Jurkat cells expressing T5Cyp S322 and H126Q have been previously described. 2016 Retrovirology Method HIV H126Q 39 44 27107820 HIV-1 capsid is involved in post-nuclear entry steps. The A105S and the N74D mutation were introduced into pCMV R8.2 using the QuikChange II XL Kit (Stratagene) as previously described. 2016 Retrovirology Method HIV A105S;N74D 4;18 9;22 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Viral vectors were produced by Fugene transfection in 293T cells using plasmids pCMV R8.2 and pMD.G as described above and used to infect Jurkat hT5Cyp S322 or H126Q cells. 2016 Retrovirology Method HIV H126Q 160 165 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. RT-RAMs were identified and analyzed by using the Stanford Drug Resistance Database for V90I, A98G, L100I/V, K101E/P/Q/H/N, K103N/S/T/Q/E/H/R, V106A/M/I, V108I, E138A/K/Q/G/R, V179D/E/T/F/L, Y181C/I/V/S/F/G, M184I, Y188C/H/L/F, G190A/S/E/Q/C/V/T, H221Y, P225H, F227C/L, M230L/I, P236L, K238T/N, Y318F and N348I. 2016 PloS one Method HIV A98G;E138A;E138G;E138K;E138Q;E138R;F227C;F227L;G190A;G190C;G190E;G190Q;G190S;G190T;G190V;H221Y;K101E;K101H;K101N;K101P;K101Q;K103E;K103H;K103N;K103Q;K103R;K103S;K103T;K238N;K238T;L100I;L100V;M184I;M230I;M230L;N348I;P225H;P236L;V106A;V106I;V106M;V108I;V179D;V179E;V179F;V179L;V179T;V90I;Y181C;Y181F;Y181G;Y181I;Y181S;Y181V;Y188C;Y188F;Y188H;Y188L;Y318F 94;161;161;161;161;161;261;261;228;228;228;228;228;228;228;247;109;109;109;109;109;124;124;124;124;124;124;124;286;286;100;100;208;270;270;305;254;279;143;143;143;154;176;176;176;176;176;88;191;191;191;191;191;191;215;215;215;215;295 98;174;174;174;174;174;268;268;245;245;245;245;245;245;245;252;122;122;122;122;122;141;141;141;141;141;141;141;293;293;107;107;213;277;277;310;259;284;152;152;152;159;189;189;189;189;189;92;206;206;206;206;206;206;226;226;226;226;300 RT 0 2 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. pNL4.3, pNL43R263K, pNL4.3H51Y/R263K, pNL4.3M184I, pNL4.3M184V, pNL4.3R263K-M184I, pNL4.3R263K-M184V, pNL4.3K65R, pNL4.3L74V, pNL4.3K103N, and pNL4.3E138K were previously constructed using site-directed mutagenesis. 2016 Retrovirology Method HIV M184I;M184V;R263K 76;95;31 81;100;36 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Similar methods were employed to produce these plasmids: pNL4.3R263K-K65R, pNL4.3H51Y/R263K-K65R, pNL4.3R263K/L74V, pNL4.3H51Y-R263K/L74V, pNL4.3R263K-K103N, pNL4.3H51Y/R263K-K103N, pNL4.3R263K-E138K, pNL4.3H51Y/R263K-E138K, pNL4.3H51Y/R263K-M184I, and pNL4.3H51Y/R263K-M184V. 2016 Retrovirology Method HIV R263K;R263K;E138K;E138K;K103N;K103N;K65R;K65R;L74V;L74V;M184I;M184V;R263K;R263K;R263K;R263K;R263K;R263K 145;188;194;218;151;175;69;92;110;133;242;270;86;127;169;212;236;264 150;193;199;223;156;180;73;96;114;137;247;275;91;132;174;217;241;269 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Analyses were therefore designed to (1) describe virologic failure and resistance in each group, (2) explore predictors of failure and resistance in the two groups as the data and sample sizes allow, and (3) examine HIV-1 subtype and associated potential genotypic pathways and mutation correlation for the development of resistance (including specifically K65R). 2016 Journal of the International AIDS Society Method HIV K65R 357 361 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Fisher's exact and Wilcoxon rank sum tests were used to compare demographic and clinical covariates of several patient subgroups: those with and without VL>40 copies/mL stratified by group; and those with and without K65R, stratified by group, among participants with genotypes. 2016 Journal of the International AIDS Society Method HIV K65R 217 221 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. To evaluate potential impacts of subtype-specific codon usage on K65R selection, we compared nucleic acids at codons 64 to 66 in subtypes A, B, C and D sequences from ART-naive or TDF-treated patients, derived from: (1) Stanford database (33) and (2) AMPATH (prior and current studies). 2016 Journal of the International AIDS Society Method HIV K65R 65 69 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The PDB IDs are 3OK9, 4HDB, 4HDP, 4HE9, and 4HDF for WT, D30N, I50V, I54M, and V82A, respectively. 2016 International journal of molecular sciences Method HIV D30N;I50V;I54M;V82A 57;63;69;79 61;67;73;83 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. p8.9NDSB wildtype (WT) and capsid mutants N74D and P90A was kindly provided by Jeremy Luban(University of Massachusetts Medical School). 2016 PLoS pathogens Method HIV N74D;P90A 42;51 46;55 Capsid 27 33 27333000 Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting. Detection and quantification of drug resistance mutations M184V, K70E and K65R when present as minor variants was performed using allele-specific PCR as described elsewhere. 2016 PloS one Method HIV K65R;K70E;M184V 74;65;58 78;69;63 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). The DeltaVpr and Vpr A30L, F34I, W54R, Q65R, and H71R mutations were created in pH and pH-AD8 using QuikChange II XL Site-Directed Mutagenesis Kit from Agilent Technologies, and the specific mutations were verified by DNA sequencing. 2016 Virology Method HIV A30L;F34I;H71R;Q65R;W54R 21;27;49;39;33 25;31;53;43;37 Vpr 17 20 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. Site-directed mutagenesis was performed to introduce AA(s) substitutions (E11K, K186E, E11K plus K186E, D116A, V165A, F181T, or A128T) into the pBiFC-INs using PrimeSTAR Max. 2016 Journal of virological methods Method HIV A128T;D116A;E11K;E11K;F181T;K186E;K186E;V165A 128;104;74;87;118;80;97;111 133;109;78;91;123;85;102;116 IN 150 153 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. In this report, the term 'transmitted drug resistance mutations' (TDRMs) is used to describe (a) for pol, the presence of one or more mutations from the World Health Organisation (WHO) 2009 surveillance list 19 with the addition of E138K, a mutation known to cause resistance to the second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, and all changes at codon T215 as they are likely to be ancestrally related to T215F or Y mutations 20; (b) for integrase, the presence of mutations from the IAS-USA 2013 list or accessory mutations reported by the Stanford HIVdb algorithm v7.0 (HIV Drug Resistance Database, Stanford University, Stanford, CA). 2017 HIV medicine Method HIV E138K;T215F 232;446 237;451 NNRTI;IN;NNRTI;Pol;Capsid 301;479;348;101;674 336;488;353;104;676 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The construction of HIV-1 PR coding region containing five stabilizing mutations (Q7K, L33I, L63I, C67A, and C95A) was described previously 44, 45. 2016 FEBS open bio Method HIV C67A;C95A;L33I;L63I;Q7K 99;109;87;93;82 103;113;91;97;85 PR 26 28 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Plasmids encoding pNL4-3 Env, pNL4-3-S40A or pNL4-3-S40F, and l-maltose binding protein (MBP)-FLAG-p6*-PR-HA have been previously described. 2016 Retrovirology Method HIV S40A;S40F 37;52 41;56 Env;Gag;PR 25;99;103 28;101;105 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. T186S, L188F, L188F/T190I mutations of HIV-1 Gag sequence were introduced into the HIV-1 subtype B NL4-3 plasmid (pNL4-3) and a patient-derived subtype C HIV-1 Gag-protease sequence (SK-254, GenBank accession number HM593258) respectively by using QuikChange Lightning site-directed mutagenesis kit (Agilent technologies) along with custom-designed mutagenesis forward and reversed primers. 2016 Retrovirology Method HIV L188F;L188F;T190I;T186S 7;14;20;0 12;19;25;5 PR;Gag;Gag 164;45;160 172;48;163 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. The customised former primers are (mutated codons shown in bold): 5'-G CAA ATG GTA CAC CAA GCC ATA TCA CCT AGA ACT TTG AAT G-3' (SK-254 Gag T147I); 5'-AA ATA GCA TGG ATG ACT AGT A AC CCA CCT ATC CCA GTG GGA G-3' (SK-254 Gag G252S/V256I); 5'-ACA CAA GAT GTA AAA AAT TGG ATG ACA GAT ACC TTG TTG GTC CAA-3' (SK-254 Gag E319D); 5'-C ATT TTA AGG GCA TTA GGA CCA GGA GCT ACG TTA GAA GAA ATG ATG ACA GCA TG-3' (SK-254 Gag A340G/S342T) Hence, the p24 Gag in this modified SK-254 sequence (SK-254(M)) is the same as Consensus C. 2016 Retrovirology Method HIV A340G;E319D;G252S;S342T;T147I;V256I 415;316;224;421;140;230 420;321;229;426;145;235 p24;Gag;Gag;Gag;Gag;Gag 439;136;220;312;411;443 442;139;223;315;414;446 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. The forward primers are shown as follows (mutated codons shown in bold): 5'-CC CCA CAA GAT TTA AAT AGC ATG CTA AAC ACA GTG GG-3' (NL4-3 Gag T186S); 5'-CA CAA GAT TTA AAT ACC ATG TTC AAC ACA GTG GGG GGA CAT CA-3' (NL4-3 Gag L188F); 5'-CCA CAA GAT TTA AAT ACC ATG TTC AAC ATA GTG GGG GGA CAT CAA GCA G-3' (NL4-3 Gag L188F/T190I); 5'-CC CCA CAA GAT TTA AAC AGC ATG CTA AAT ACA GTG GG-3' (SK-254 Gag T186S); 5'-CA CAA GAT TTA AAC ACC ATG TTC AAT ACA GTG GGG GGA CAT CA-3' (SK-254 Gag L188F); 5'-CCA CAA GAT TTA AAC ACC ATG TTC AAT ATA GTG GGG GGA CAT CAA GCA G-3' (SK-254 Gag L188F/T190I). 2016 Retrovirology Method HIV L188F;L188F;L188F;L188F;T186S;T186S;T190I;T190I 223;314;480;572;140;396;320;578 228;319;485;577;145;401;325;583 Gag;Gag;Gag;Gag;Gag;Gag;Capsid;Capsid;Capsid;Capsid 136;219;310;392;476;568;151;206;407;462 139;222;313;395;479;571;153;208;409;464 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. The other mutations Q182S, T190A, T190I, T186S/Q182S, T186S/T190A, and T186S/T190I were kindly engineered and provided by Dr. 2016 Retrovirology Method HIV Q182S;Q182S;T186S;T186S;T186S;T190A;T190A;T190I;T190I 20;47;41;54;71;27;60;34;77 25;52;46;59;76;32;65;39;82 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Multi-NRTI resistance mutations were defined as either presence of K65R or 3 or more TAMs or presence of M184V along with 2 TAMs. 2016 Medicine Method HIV K65R;M184V 67;105 71;110 NRTI 6 10 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant viruses encoding RT mutation K103N, Y181C, Y188L, or L100I/Y181C were constructed by site-directed mutagenesis. 2016 Antimicrobial agents and chemotherapy Method HIV K103N;L100I;Y181C;Y181C;Y188L 97;121;104;127;111 102;126;109;132;116 NNRTI;NNRTI;RT 4;51;85 39;56;87 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The NRTI-resistant viruses encoding RT mutation M184V were constructed by site-directed mutagenesis. 2016 Antimicrobial agents and chemotherapy Method HIV M184V 48 53 NRTI;RT 4;36 8;38 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The nucleoside reverse transcriptase inhibitor (NRTI)-resistant viruses encoding reverse transcriptase (RT) mutation K65R were obtained from Mark Wainberg (McGill AIDS Center, Montreal, Canada). 2016 Antimicrobial agents and chemotherapy Method HIV K65R 117 121 NRTI;RT;NRTI;RT 4;81;48;104 36;102;52;106 AIDS 163 167 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The protease inhibitor (PI)-resistant mutant viruses encoding mutations in the HIV-1 protease-coding sequence, L10F/M46I/I50V, I84V/L90M, G48V/I54V/V82S, and G48V/V82A/L90M, were produced in electroporated SupT1 cells via homologous recombination. 2016 Antimicrobial agents and chemotherapy Method HIV G48V;G48V;I50V;I54V;L10F;L90M;M46I;V82A;V82S;I84V;L90M 138;158;121;143;111;168;116;163;148;127;132 142;162;125;147;115;172;120;167;152;131;136 PR;PR;PI 4;85;24 12;93;26 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The virus 6TAMs, containing six resistance mutations in HIV-1 RT (M41L, D67N, K70R, L210W, T215Y, and K219Q) that confer resistance to thymidine analogs, was constructed by cloning a PCR-amplified RT-encoding fragment from HIV-infected patient-derived plasma. 2016 Antimicrobial agents and chemotherapy Method HIV D67N;K219Q;K70R;L210W;M41L;T215Y 72;102;78;84;66;91 76;107;82;89;70;96 RT;RT 62;197 64;199 HIV infections 223 235 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. HeLa cells (4 x 104) were seeded overnight on cover glass in 12-well plates before transfection for 48 h with 0.8 mug of pCAGGS/Gag and 1.5 mug of pCAGGS/eCFP-TSG101 without/with 0.5 mug of pCAGGS/HA-Vpr, 0.5 mug of pCAGGS/HA-Vpr A30F, or 0.5 mug of pCAGGS/Vif-HA plasmids. 2016 PloS one Method HIV A30F 230 234 Vif;Vpr;Vpr;Gag 257;200;226;128 260;203;229;131 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. VLPs were produced by transfection of HEK293T cells (8.3 x 105 in 6-well plates) with 0.8 mug of pCAGGS/Gag and 1.5 mug of pCAGGS/FLAG-TSG101, either without/with the indicated amount of pCAGGS/Vpr or pCAGGS/Vpr A30F plasmids for 48 h (see the Figures). 2016 PloS one Method HIV A30F 212 216 Vpr;Vpr;Gag 194;208;104 197;211;107 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Full-length WT and two mutant RT proteins (K103N and Y181C) were expressed in Escherichia coli BL21 (DE3) cells and purified as described previously. 2016 Viruses Method HIV K103N;Y181C 43;53 49;58 RT 30 32 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Plasmids to express mutant envelopes, pCXN-JR-FLV38A, pCXN-JR-FLQ40H, pCXN-JR-FLN43D, pCXN-JR-FLC34r (I37K/N126K/L204I), pCXN-JR-FLSC34r (I37K/R46K/Q52R/Q56R/N126K/S138A/E151K/K154N/L204I/L210F), and pCXN-JR-FLSC34EKr (Q41R/N43K/A96D/N126K/V182I/P203S/L204I/H258Q/A312T) were constructed by oligonucleotide-based site-directed mutagenesis with pCXN-JR-FL (kindly provided by Dr. 2016 Retrovirology Method HIV A312T;A96D;E151K;H258Q;I37K;I37K;K154N;L204I;L204I;L204I;L210F;N126K;N126K;N126K;N43K;P203S;Q41R;Q52R;Q56R;R46K;S138A;V182I 264;229;170;258;102;138;176;113;182;252;188;107;158;234;224;246;219;148;153;143;164;240 269;233;175;263;106;142;181;118;187;257;193;112;163;239;228;251;223;152;157;147;169;245 Env 27 36 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Single and double mutants of C34r mutations, I37K, N126K, and L204I, were constructed by PCR and subsequent homologous recombination using the GeneArt seamless cloning an assembly enzyme mix (Invitrogen). 2016 Retrovirology Method HIV I37K;L204I;N126K 45;62;51 49;67;56 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The extracellular portion of the HIV-1JR-FL gp41 structures with and without an I37K mutation were constructed by using the homology modeling method with Molecular Operating Environment (Chemical Computing Group Inc., Montreal, QC, Canada). 2016 Retrovirology Method HIV I37K 80 84 gp41 44 48 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Env sequences from HIV-2 wild type (WT), Env 1-749 and Env N659D were amplified with primers including the restriction sites HindIII and NheI (for env WT and env N659D: 5'-AAGCTTATGATGAATCAGCTGCTTATTGCC-3'; 5'-GCTAGCCAGGAGGGCGATTTCTG-3', and for env 1-749: 5'-GCTAGCGGGCCAGTATCTGTCTCCAC-3' reverse primer) by taking care to remove the stop codon in the env sequence in order to enable the correct expression of the fused protein. 2016 Viruses Method HIV N659D;N659D 59;162 64;167 Env;Env;Env;Env;Env;Env;Env 0;41;55;147;158;246;353 3;44;58;150;161;249;356 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. HEK293T cells (5 x 105) were co-transfected with the following combination of constructed expression plasmids: 500 ng of plasmid expressing BST-2-Clover fusion protein and 1 mug of plasmid expressing Env-mRuby2 (or Env 1-749-mRuby2 or Env N659D-mRuby2) fusion proteins. 2016 Viruses Method HIV N659D 239 244 Env;Env;Env 200;215;235 203;218;238 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Besides these three major mutations, the integrase substitutions with a Stanford HIVdb score 10 to at least one INSTI were included, such as H51Y, T66A/I/K, L74M, E92G/Q/V, Q95K, T97A, F121Y, E138A/K, G140S/C/A, Y143G/K/S/A, P145S, Q146P, S147G, V151A/L, S153F/Y, N155S/T, E157Q, G163 K/R, S230R, and R263K. 2016 Scientific reports Method HIV E138A;E138K;E157Q;E92G;E92Q;E92V;F121Y;G140A;G140C;G140S;G163K;G163R;H51Y;L74M;N155S;N155T;P145S;Q146P;Q95K;R263K;S147G;S153F;S153Y;S230R;T66A;T66I;T66K;T97A;V151A;V151L;Y143A;Y143G;Y143K;Y143S 194;194;275;165;165;165;187;203;203;203;282;282;143;159;266;266;227;234;175;303;241;257;257;292;149;149;149;181;248;248;214;214;214;214 201;201;280;173;173;173;192;212;212;212;290;290;147;163;273;273;232;239;179;308;246;264;264;297;157;157;157;185;255;255;225;225;225;225 IN;INSTI 41;114 50;119 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Some amino acid substitutions (H51L/R, L74V, P145R, V151I, and S230N) that have been described in more than 2% of the study population in previous studies or this study were also included for analysis. 2016 Scientific reports Method HIV H51L;H51R;L74V;P145R;S230N;V151I 31;31;39;45;63;52 37;37;43;50;68;57 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. The major INSTI mutations, which have been determined having a marked reduction of viral susceptibility to raltegravir and elvitegravir, include Y143C/H/R, Q148H/K/R, and N155H. 2016 Scientific reports Method HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 171;156;156;156;145;145;145 176;165;165;165;154;154;154 INSTI 10 15 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Backbone resonance assignments for the two mutants of p17 (E12A and L85A) were independently made at 25 C using 3D CBCA(CO)NH, HNCACB, HNCO, HN(CA)CO, HNCA, and HN(CO)CA. 2016 PloS one Method HIV E12A;L85A 59;68 64;72 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In the case of the dynamic structure of E12A at pH 5.5, isotropic tumbling was assumed for the calculation. 2016 PloS one Method HIV E12A 40 44 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In the model-free approach, assuming anisotropic tumbling, the internal mobility of residues was characterized by the order parameter S2 for the dynamics of WT and E12A at pH 7. 2016 PloS one Method HIV E12A 164 168 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Recombinant WT p17 protein and two mutants, E12A and L85A, were produced for NMR studies. 2016 PloS one Method HIV E12A;L85A 44;53 48;57 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The average values of the rate constants for the fast exchangeable amide protons were calculated to compare the exchange rates between WT and E12A at pH 7. 2016 PloS one Method HIV E12A 142 146 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Chi-square tests were used to compare the percentage of individuals with detectable viral load and percentage of individuals on cART between the C31S and C31C groups. 2017 Journal of neurovirology Method HIV C31C;C31S 154;145 158;149 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. For the C31S and the C31C groups, t tests were conducted to compare average CD4 counts, log10 viral load, duration of infection (in months), and self-reported depression using the CES-D. 2017 Journal of neurovirology Method HIV C31C;C31S 21;8 25;12 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. HIV+ individuals included 37 individuals with HIV-C with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls. 2017 Journal of neurovirology Method HIV C31C;C31S 136;65 140;69 Tat;Tat 61;118 64;121 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Nucleotide sequences were translated into amino acid sequences and the C30C31 motif or C31S mutation was recorded. 2017 Journal of neurovirology Method HIV C31S 87 91 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. These analyses were repeated to compare C31S and C31C individuals. 2017 Journal of neurovirology Method HIV C31C;C31S 49;40 53;44 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. In particular, the Wayne test accurately predicted the PZA resistance of our two most prevalent mutations (13/14 in agreement for D49N and 4/4 in agreement for T135P) and our wild-type isolates (52/55 in agreement). 2016 The American journal of tropical medicine and hygiene Method HIV D49N;T135P 130;160 134;165 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. Mutations K26R and H42/H43-N were generated in the pcDNAhVif plasmid by Quick-Change Site-directed Mutagenesis (Agilent Technologies). 2016 Scientific reports Method HIV K26R 10 14 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. pCMV-hA3G SL1 (deletion of nucleotides 112 to 297, 112-297), SL2 ( 1-128 and 199-297), SL3 ( 1-207), SL1SL2 ( 199-297) and SL2SL3 ( 1-127) were generated by Quick-Change Site-directed Mutagenesis (Agilent Technologies) based on the secondary structure model of the 5'-UTR of hA3G mRNA and deletions were confirmed by DNA sequencing (GATC Biotech, Germany). 2016 Scientific reports Method HIV del 112 15 43 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. DNA sequencing of CD4 revealed a N64I mutation, which however had no influence on the fusion capacity of CD4 and it was therefore used. 2016 Pharmacology research & perspectives Method HIV N64I 33 37 28195728 Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K. The PRTM has substitutions V32I, I47V and V82I associated with drug resistance, which are in addition to five stabilizing substitutions Q7K, L33I, L63I, C67A and C95A. 2017 Journal of medicinal chemistry Method HIV C67A;C95A;I47V;L33I;L63I;Q7K;V32I;V82I 153;162;33;141;147;136;27;42 157;166;37;145;151;139;31;46 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. All patients that withdrew consent and/or had the T97A integrase mutation at a non-protocol-defined virologic failure visit(s) have been excluded from previously reported efficacy analyses and thus were excluded from treatment outcome analyses described in this report. 2017 PloS one Method HIV T97A 50 54 IN 55 64 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. All patients with the T97A integrase mutation at protocol-defined virologic failure visit(s) have been previously reported in study-specific resistance analysis populations. 2017 PloS one Method HIV T97A 22 26 IN 27 36 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Fisher's exact test was used to compare the frequency of the T97A integrase mutation between patient populations. 2017 PloS one Method HIV T97A 61 65 IN 66 75 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, due to the limited number of patients with the T97A integrase mutation, all patients were included in phenotypic resistance analyses irrespective of protocol-defined status. 2017 PloS one Method HIV T97A 56 60 IN 61 70 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. On-treatment analyses of integrase sequences considered only the first confirmed protocol-defined virologic failure visit with persistent (no change from pre-treatment integrase sequence) or emergent (change from pre-treatment integrase sequence) T97A integrase mutation, irrespective of preceding or concurrent resistance to other co-administered antiretrovirals. 2017 PloS one Method HIV T97A 245 251 IN;IN;IN;IN 25;168;227;252 34;177;236;261 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Primary INSTI RAMs against EVG and/or RAL were based on IAS-USA Guidelines of RAMs with some modifications to remove secondary INSTI RAMs (i.e., L74M, F121Y, E138A/K, and G140A/S) (Fig 1). 2017 PloS one Method HIV E138A;E138K;F121Y;G140A;G140S;L74M 158;158;151;171;171;145 165;165;156;178;178;149 INSTI;INSTI 8;127 13;132 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Sequences of the entire integrase gene derived from HIV-infected patients screened and/or enrolled across multiple clinical studies (Table 1) were analyzed for pre-existence or emergence of the T97A mutation using the HIV-1NL4-3 (subtype B) integrase sequence as a reference. 2017 PloS one Method HIV T97A 194 198 IN;IN 24;241 33;250 HIV infections 52 64 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. To determine the background sequencing error rate, DNA plasmids of HXB2 and HXB2 with site-directed mutant K103N were included, directly and after nested PCR. 2017 Clinical infectious diseases Method HIV K103N 107 112 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. 2017 Scientific reports Method HIV K65R 93 97 RT;RT 38;133 59;155 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Mutations found in the triple mutant K65R/Q151M/M184V were orderly added starting from mutant K65R, and then introducing mutation Q151M, and finally M184V. 2017 Scientific reports Method HIV K65R;M184V;Q151M;K65R;M184V;Q151M 37;48;42;94;149;130 41;53;47;98;154;135 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The mutagenic primers used were: 5'-CATTTGCAATCAAGAGAAAGGACAAAAAC-3' and 5'-GTTTTTGTCCTTTCTCTTGATTGCAAAT-3' for K65R, 5'-TAAAGTCTTGCCAATGGGATGGAAGGGA-3' and 5'-TCCCTTCCATCCCATTGGCAAGACTTTA-3' for Q151M, and 5'-ATTATCATTCAGTACGTGGATGATATCT-3' and 5'-AGATATCATCCACGTACTGAATGATAAT-3' for M184V. 2017 Scientific reports Method HIV K65R;M184V;Q151M 112;285;196 116;290;201 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. The F1Pk and 6/5AL aptamers and arbitrary control were 5'-end labeled with 32P-ATP and polynucleotide kinase, then added to solutions containing various concentrations of subtype B RT or the R277K point mutant (0, 0.1, 0.3, 1, 3, 10, 100 or 300 nM final concentrations) in binding buffer (140 mM KCl, 1 mM MgCl2, 50 mM Tris-HCl, pH 7.5). 2017 Nucleic acids research Method HIV R277K 191 196 RT 181 183 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Because of the possibility that some individuals may have received a thymidine analog before receiving a TDF-containing regimen, as such switches may not have always reported, we excluded from our analysis individuals with sequences containing one or more canonical thymidine analogue mutations (TAMs) - M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E. 2017 EBioMedicine Method HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 310;342;342;316;322;304;329;329 314;349;349;320;327;308;336;336 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The mutational covariates included number of TRAMs, number of NRTI-associated TRAMs, number of NNRTI-associated TRAMs, M184V, K65R, K70E/Q/T/N, and K65R in combination with its mutational partners (defined as mutations with which K65R was significantly correlated in our covariation analysis). 2017 EBioMedicine Method HIV K65R;K65R;K65R;K70E;K70N;K70Q;K70T;M184V 126;148;230;132;132;132;132;119 130;152;234;142;142;142;142;124 NNRTI;NRTI 95;62 100;66 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The generation of the R263K and H51Y/R263K integrase and K65R reverse transcriptase mutants from pNL4.3 has been described previously. 2017 mBio Method HIV H51Y;K65R;R263K;R263K 32;57;22;37 36;61;27;42 RT;IN 62;43 83;52 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The R263K dolutegravir resistance-associated substitution progressively decreases HIV-1 integration. 2017 mBio Method HIV R263K 4 9 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. If the K65R mutation was ever detected (including as a mixture with WT) in an individual patient, the complete ART history until the first sample with this mutation was considered; if K65R was never detected, the patient's complete ART history until the last sample was considered. 2017 The Journal of antimicrobial chemotherapy Method HIV K65R;K65R 7;184 11;188 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Interaction terms between subtype and current NRTI exposure were fitted to examine if the effect of subtype on the likelihood of detection of K65R depended on the specific NRTI being prescribed; subtype B and subtypes non-B/C were grouped for this analysis. 2017 The Journal of antimicrobial chemotherapy Method HIV K65R 142 146 NRTI;NRTI 46;172 50;176 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Multivariate logistic regression models were fitted to assess the association between viral subtype and the detection of K65R, adjusting for ART history as described above. 2017 The Journal of antimicrobial chemotherapy Method HIV K65R 121 125 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Patients were considered eligible for the analysis if the following criteria were met: (i) clinical care was received at a centre participating in the UK Collaborative HIV Cohort (UK CHIC) Study (detailed clinical and demographic data, including a complete ART history, are provided by these centres to which resistance test results are regularly linked); (ii) at least one (non-WT) resistance test had been conducted after ART initiation; (iii) K65R had not been detected in any tests conducted prior to ART initiation; and (iv) viral subtype could be assigned based on the nucleotide sequence from a resistance test (see section below). 2017 The Journal of antimicrobial chemotherapy Method HIV K65R 444 450 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The propensity for subtype C to develop K65R appears to be due to polymorphisms at positions 64 and 65 rather than any other subtype characteristic. 2017 The Journal of antimicrobial chemotherapy Method HIV K65R 40 44 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The specific NRTIs were chosen a priori on the basis that they were known to select for K65R (tenofovir, abacavir, didanosine and stavudine) or to protect against the development of K65R (zidovudine) due to antagonistic mutational interactions. 2017 The Journal of antimicrobial chemotherapy Method HIV K65R;K65R 88;182 92;186 NRTI 13 18 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. In particular, a list of 50 NNRTI resistance-associated mutations (RAMs) was compiled (including G190T) for analysis of NNRTI resistance. 2017 SAGE open medicine Method HIV G190T 97 102 NNRTI;NNRTI 28;120 33;125 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. Association of antiretroviral and L74V/I mutations were assessed by the Fisher's exact test. 2017 The Pediatric infectious disease journal Method HIV L74I;L74V 34;34 40;40 28383402 Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice. Among VF patients we examined the frequency of common resistance mutations: K103N, M184 V/I, K65R, and thymidine analog mutations. 2017 Medicine Method HIV K103N;K65R;M184I;M184V 76;93;83;83 81;97;91;91 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. TatC (lack Ser46Phe) and Tat variants (TatN12, TatD60, TatVT6) were cloned into: (a) mammalian expression vector pCMV-myc vector (Clonetech) under the CMV promoter for functional studies, and (b) prokaryotic expression vector pGEX-4T-2 (Invitrogen) to obtain GST-tagged proteins. 2017 Frontiers in microbiology Method HIV S46F 11 19 Tat;Tat;Tat 25;39;47 28;42;50 28604824 Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. Participants were (perinatally or non perinatally) HIV-infected children, adolescents, and young adults >=8 to <25 years old, on a non-NNRTI (non-nucleoside reverse transcriptase inhibitor) regimen for at least 6 months, with documented nonadherence (e.g., self-report or pharmacy report, despite documented interventions to improve nonadherence), M184V resistance mutation at or prior to screening on standard, clinically available genotyping assays, absolute CD4+ T cell count >=100 cells/mm3, and VF (defined as HIV-1 plasma RNA >=400 copies/mL on at least two occasions including screening at least 2 months after initiating the regimen and within 6 months of study entry). 2017 PloS one Method HIV M184V 348 353 NNRTI;NNRTI 142;135 178;140 HIV infections 51 63 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Analyses of reverse transcriptase-E138X and HLA-B*18 frequencies were limited to countries with a minimum of 100 HIV-1 sequences; 43 countries were thus represented in both reverse transcriptase-E138X and HLA data sets. 2017 AIDS (London, England) Method HIV E138X;E138X 34;195 39;200 RT;RT 12;173 33;194 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Differences in p24 Gag production by wild-type versus reverse transcriptase-E138X-containing HIV-1 strains in the viral replication assay was assessed using student's t-test. 2017 AIDS (London, England) Method HIV E138X 76 81 RT;p24;Gag 54;15;19 75;18;22 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Plasma HIV-1 RNA-derived reverse transcriptase sequences linked to high-resolution HLA-B typing data from 7647 chronically HIV-infected, ART-naive individuals from 15 established contemporary cohorts in Canada, United States, Mexico, Belize, Guatemala, Honduras, Nicaragua, Panama, United Kingdom, Uganda, Botswana, South Africa, Japan, Vietnam, and Australia, and one published study including 125 HLA-B locus typed, chronically HIV-infected, ART-naive individuals from France (retrieved via a PubMed search of English language articles published between 2010 and 2015 using keywords 'HIV' and 'resistance' that yielded 6803 articles, of which only this one featured linked reverse transcriptase-E138X and B*18 frequency data) were analyzed with respect to reverse transcriptase-E138X and HLA-B*18 carriage. 2017 AIDS (London, England) Method HIV E138X;E138X 697;780 702;785 RT;RT;RT 25;675;758 46;696;779 HIV infections;HIV infections 123;430 135;442 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X and human leukocyte antigen-B*18 frequencies in global cohorts (linked analysis) 2017 AIDS (London, England) Method HIV E138X 22 27 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X and human leukocyte antigen-B*18 frequencies in global cohorts (linked analysis). 2017 AIDS (London, England) Method HIV E138X 22 27 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X and human leukocyte antigen-B*18 frequencies in global databases (unlinked analysis) 2017 AIDS (London, England) Method HIV E138X 22 27 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X and human leukocyte antigen-B*18 frequencies in global databases (unlinked analysis). 2017 AIDS (London, England) Method HIV E138X 22 27 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. The association between reverse transcriptase-E138X and B*18 carriage in all study cohorts, overall and stratified by HIV-1 subtype, was assessed using Fisher's exact test. 2017 AIDS (London, England) Method HIV E138X 46 51 RT 24 45 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. The correlation between reverse transcriptase-E138X prevalence and HLA-B*18 frequency was evaluated using Spearman's rank correlation. 2017 AIDS (London, England) Method HIV E138X 46 51 RT 24 45 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. To delineate the effect of reverse transcriptase-E138X on viral replication capacity, recombinant HIV-1's were produced in the subtype B NL4-3 reference backbone (HIV-1NL4-3) and single-strain HIV-1 replication assays were performed as described in. 2017 AIDS (London, England) Method HIV E138X 49 54 RT 27 48 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. To further delineate the effect of reverse transcriptase-E138X, competitive HIV-1 replication assays were also performed. 2017 AIDS (London, England) Method HIV E138X 57 62 RT 35 56 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Unlinked reverse transcriptase-E138X and HLA-B*18 frequencies were additionally retrieved from the Stanford University HIV Drug Resistance and Allele Frequencies databases, respectively, using custom Python web scripts. 2017 AIDS (London, England) Method HIV E138X 31 36 RT 9 30 28679441 HIV-1 genetic diversity and primary drug resistance mutations before large-scale access to antiretroviral therapy, Republic of Congo. In addition, one sample (CgCHU38) from a patient attending the Centre Hospitalier et Universitaire de Brazzaville (CHU-B) and subtyped as G in all 3 regions has the mutations Y181C, M41L and T215Y. 2017 BMC research notes Method HIV M41L;T215Y;Y181C 182;191;175 186;196;180 28679441 HIV-1 genetic diversity and primary drug resistance mutations before large-scale access to antiretroviral therapy, Republic of Congo. Other minor mutations were also found, and the most prevalent were at positions V35 (98%), D177 (76%), V60 (62%), Q174 (58%), D123 (50%), T39 (48%), V135 (34%), K173 (33%), K13R (26%), D121 (24%) and other less prevalent mutations. 2017 BMC research notes Method HIV K13R 173 177 28679441 HIV-1 genetic diversity and primary drug resistance mutations before large-scale access to antiretroviral therapy, Republic of Congo. Regarding the reverse transcriptase segment, the following resistance-related mutation, M230L (n = 1, 2%), which is associated with a high level of resistance to delavirdine and nevirapine and causes an intermediate resistance to efavirenz and etravirine, was observed in one sample from Pointe-noire (CgAS23) involving the genomic complex structure gagCRF37/envA/polCRF37/A/CRF37. 2017 BMC research notes Method HIV M230L 88 93 RT 14 35 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Cells were exposed to VSV-G pseudotyped HIV-1 LAIDeltaenv WT (25 ng CAp24/106 cells) or mutant N74D (50 ng CAp24/106 cells), for 3 hours at 37 C. 2017 PLoS pathogens Method HIV N74D 95 99 Capsid;Capsid 68;107 70;109 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. For infections, 13ml of 1G5 cells (~0.9x106/ml) were mixed with 2ml NL4-3 (WT or N74D). 2017 PLoS pathogens Method HIV N74D 81 85 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Three flasks containing Jurkat cells (30 mls at 0.8x106/ml) were independently infected with VSV-G pseudotyped LAIDeltaenv WT or N74D at an MOI of 0.2 in the presence of DMSO or 400nM digoxin. 2017 PLoS pathogens Method HIV N74D 129 133 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. WT and N74D viruses were pre-mixed at 4 C at a ratio to have approximately 10% of cells infected with each virus. 2017 PLoS pathogens Method HIV N74D 7 11 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Purified endotoxin-free recombinant HIV-1 matrix protein p17, S75X and p17R76G were produced as previously described. 2017 Scientific reports Method HIV S75X 62 66 Matrix 42 48 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Raji cells, starved for 24 hours by serum deprivation, were stimulated or not with refp17, p17R76G and S75X (0.05, 0.1, 0.5 mug/ml) for 5 min, then lysed and prepared for KinexTM Antibody Microarray (KAM-850) according to manufacturer's instructions (Kinexus Bioinformatics Corporation). 2017 Scientific reports Method HIV S75X 103 107 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The lysates of cells stimulated with refp17, p17R76G and S75X (0.1 mug/ml) for 5 min were sent to Kinexus Bioinformatics Corporation for processing by Kinex KAM-850 Antibody Microarray, which contains 517 pan-specific and 337 phoshpo-site-specific probes, which recognize different epitopes on 466 proteins. 2017 Scientific reports Method HIV S75X 57 61 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The mutated matrix protein p17R76G, in which the arginine in position 76 was replaced by a glycine, was generated from p17 sequence by using Quick Change Site-directed mutagenesis Kit (Stratagene). 2017 Scientific reports Method HIV R76G 49 98 Matrix 12 18 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The structures of refp17 were obtained from the Protein Data Bank (PDB) code 1TAM, whereas homology modeling (Modeler) was used to obtain the structures of S75X and p17R76G. 2017 Scientific reports Method HIV S75X 156 160 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Primary INSTI-R substitutions assessed were T66A/I/K, E92G/Q, T97A, Y143C/H/R, S147G, Q148H/K/R, and N155H/S in IN. 2017 HIV clinical trials Method HIV E92G;E92Q;N155H;N155S;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;T97A;Y143C;Y143H;Y143R 54;54;101;101;86;86;86;79;44;44;44;62;68;68;68 60;60;108;108;95;95;95;84;52;52;52;66;77;77;77 INSTI;IN 8;112 13;114 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Primary NNRTI-R substitutions assessed were V90I, A98G, L100I, K101E/H/P, K103N/S, V106A/I/M, V108I, E138A/G/K/Q/R, V179D/F/L/T, Y181C/I/V, Y188C/H/L, G190A/E/Q/S, H221Y, P225H, F227C, and M230I/L in RT. 2017 HIV clinical trials Method HIV A98G;E138A;E138G;E138K;E138Q;E138R;F227C;G190A;G190E;G190Q;G190S;H221Y;K101E;K101H;K101P;K103N;K103S;L100I;M230I;M230L;P225H;V106A;V106I;V106M;V108I;V179D;V179F;V179L;V179T;V90I;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 50;101;101;101;101;101;178;151;151;151;151;164;63;63;63;74;74;56;189;189;171;83;83;83;94;116;116;116;116;44;129;129;129;140;140;140 54;114;114;114;114;114;183;162;162;162;162;169;72;72;72;81;81;61;196;196;176;92;92;92;99;127;127;127;127;48;138;138;138;149;149;149 NNRTI;RT 8;200 13;202 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Primary NRTI-R substitutions assessed were M41L, A62V, K65R, D67N, T69 insertions, K70E/R, L74I/V, V75I, F77L, Y115F, F116Y, Q151M, M184V/I, L210W, T215F/Y, and K219E/N/Q/R in RT. 2017 HIV clinical trials Method HIV A62V;D67N;F116Y;F77L;K219E;K219N;K219Q;K219R;K65R;K70E;K70R;L210W;L74I;L74V;M184I;M184V;M41L;Q151M;T215F;T215Y;V75I;Y115F 49;61;118;105;161;161;161;161;55;83;83;141;91;91;132;132;43;125;148;148;99;111 53;65;123;109;172;172;172;172;59;89;89;146;97;97;139;139;47;130;155;155;103;116 NRTI;RT 8;176 12;178 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Primary PI-R substitutions assessed were D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54L/M, Q58E, T74P, L76V, V82A/F/L/S/T, I84V, N88S, and L90M in PR. 2017 HIV clinical trials Method HIV D30N;G48V;I47A;I47V;I50L;I50V;I54L;I54M;I84V;L33F;L76V;L90M;M46I;M46L;N88S;Q58E;T74P;V32I;V82A;V82F;V82L;V82S;V82T 41;75;67;67;81;81;89;89;129;53;109;145;59;59;135;97;103;47;115;115;115;115;115 45;79;73;73;87;87;95;95;133;57;113;149;65;65;139;101;107;51;127;127;127;127;127 PI;PR 8;153 10;155 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Secondary INSTI-R substitutions assessed were M50I, H51Y, L68I/V, V72A/N/T, L74M, Q95K/R, G118R, S119P/R/T, F121C/Y, A128T, E138A/K, G140A/C/S, P145S, Q146I/K/L/P/R, V151A/L, S153A/F/Y, E157K/Q, G163K/R, E170A, and R263K in IN. 2017 HIV clinical trials Method HIV A128T;E138A;E138K;E157K;E157Q;E170A;F121C;F121Y;G118R;G140A;G140C;G140S;G163K;G163R;H51Y;L68I;L68V;L74M;M50I;P145S;Q146I;Q146K;Q146L;Q146P;Q146R;Q95K;Q95R;R263K;S119P;S119R;S119T;S153A;S153F;S153Y;V151A;V151L;V72A;V72N;V72T 117;124;124;186;186;204;108;108;90;133;133;133;195;195;52;58;58;76;46;144;151;151;151;151;151;82;82;215;97;97;97;175;175;175;166;166;66;66;66 122;131;131;193;193;209;115;115;95;142;142;142;202;202;56;64;64;80;50;149;164;164;164;164;164;88;88;220;106;106;106;184;184;184;173;173;74;74;74 INSTI;IN 10;224 15;226 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. For the yeast-two-hybrid (Y2H) analysis, the HIV-1 protein or GAPDH coding regions were cloned into the EcoRI and BamHI sites of pGBKT7 or pGADT7, respectively (Clontech Laboratories, Inc.). 2016 Biochemistry and biophysics reports Method HIV Y2H 26 29 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The K43R and N323tc mutants were obtained by introducing each mutation into the cognate T/F IMC as previously described. 2017 Retrovirology Method HIV K43R 4 8 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. INPFV mutants (D128N, D185N, E221A, G187R, F190Y and S217K) were constructed using the QuikChange Lightning site-directed mutagenesis kit (Agilent) according to manufacturer's instructions. 2017 Scientific reports Method HIV D128N;D185N;E221A;F190Y;G187R;S217K 15;22;29;43;36;53 20;27;34;48;41;58 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. The full-length wt INPFV, the three single mutants of the catalytic triad (D128N, D185N, E221A) and RAL/DTG-resistant mutants (G187R, F190Y, S217K) were expressed using E. 2017 Scientific reports Method HIV D128N;D185N;E221A;F190Y;G187R;S217K 75;82;89;134;127;141 80;87;94;139;132;146 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Analysis of pol sequences showed that 11 of these 32 subjects (34.3%) were infected with viruses harboring major DRMs, including major resistance mutations to NRTIs such as D67N, K70R, M184V, K219Q/E, T215F, and T69N; and major resistance mutations to NNRTIs such as Y181C, K103N, V106A/M, P225H, Y188L, H221Y, V108I, L100I (Tables 2 and 3). 2017 Scientific reports Method HIV D67N;H221Y;K103N;K219E;K219Q;K70R;L100I;M184V;P225H;T215F;T69N;V106A;V106M;V108I;Y181C;Y188L 173;304;274;192;192;179;318;185;290;201;212;281;281;311;267;297 177;309;279;199;199;183;323;190;295;206;216;288;288;316;272;302 NNRTI;NRTI;Pol 252;159;12 258;164;15 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Analysis of the P2/NC Gag cleavage site showed the following mutations: S373A/T/Q/P, A374T/S/N/G/P/V/H/Q, T375S/G/N/A/P/H/I, I376V/M/A, M377L, M378I/L/V, R380K/G, G381S/N, and N382K. 2017 Scientific reports Method HIV A374G;A374H;A374N;A374P;A374Q;A374S;A374T;A374V;G381N;G381S;I376A;I376M;I376V;M377L;M378I;M378L;M378V;N382K;R380G;R380K;S373A;S373P;S373Q;S373T;T375A;T375G;T375H;T375I;T375N;T375P;T375S 85;85;85;85;85;85;85;85;163;163;125;125;125;136;143;143;143;176;154;154;72;72;72;72;106;106;106;106;106;106;106 104;104;104;104;104;104;104;104;170;170;134;134;134;141;152;152;152;181;161;161;83;83;83;83;123;123;123;123;123;123;123 Gag;NC 22;19 25;21 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Eleven of these 12 subjects with >=3 mutations in the Gag P2/NC cleavage site also had secondary PIs resistance mutations, including 10 subjects with K20I (Table 5). 2017 Scientific reports Method HIV K20I 150 154 Gag;NC;PI 54;61;97 57;63;100 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Four subjects on ART also had viruses harboring the NNRTIs secondary mutations V179D, A98G, E138A, V179E, and F227L, including subject NA2CMR151 who had both A98G and the major NNRTI resistance mutation Y181C. 2017 Scientific reports Method HIV A98G;A98G;E138A;F227L;V179D;V179E;Y181C 86;158;92;110;79;99;203 90;162;97;115;84;104;208 NNRTI;NNRTI 52;177 58;182 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K103N was the most frequent NNRTIs resistance mutation detected and was present in 4 of the 8 naive patients (50%) (Table 3). 2017 Scientific reports Method HIV K103N 0 5 NNRTI 28 34 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. M184V was the most frequent NRTIs resistance mutation and was detected in 3 of the 8 patients (37.5%) (Table 3). 2017 Scientific reports Method HIV M184V 0 5 NRTI 28 33 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Most of the subjects with major resistance mutation to NRTIs and/or NNRTIs harbored viruses that also had secondary resistance mutations to PIs: L10I, V11I, K20V, and K20I (Table 2). 2017 Scientific reports Method HIV K20I;K20V;L10I;V11I 167;157;145;151 171;161;149;155 NNRTI;NRTI;PI 68;55;140 74;60;143 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Naive subjects showed some mutations in the P2/NC cleavage site that were absent in ART-experienced patients, including S373P, A374G/V/H/Q, T375P/H/I, I376A, M377L, and M378L/V. 2017 Scientific reports Method HIV A374G;A374H;A374Q;A374V;I376A;M377L;M378L;M378V;S373P;T375H;T375I;T375P 127;127;127;127;151;158;169;169;120;140;140;140 138;138;138;138;156;163;176;176;125;149;149;149 NC 47 49 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. None of the 4 subjects on second line ART harbored viruses with major resistance mutation to PIs, but one of these subjects (NACMR039) harbored viruses with major resistance mutations to both NRTIs and NNRTIs, and a minor/secondary resistance mutation to PIs (K20I) (Table 2). 2017 Scientific reports Method HIV K20I 260 264 NNRTI;NRTI;PI;PI 202;192;93;255 208;197;96;258 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Of the subjects analyzed, 16 (11.67%), 8 (5.83%), and 1 (0.72%) harbored viruses with T375A, S373Q, and S373P mutations respectively in the P2/NC cleavage site. 2017 Scientific reports Method HIV S373P;S373Q;T375A 104;93;86 109;98;91 NC 143 145 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Other major NNRTIs resistance mutations detected included Y181C, V108I, P225H, L100I, K101E, and Y188L (Table 3). 2017 Scientific reports Method HIV K101E;L100I;P225H;V108I;Y181C;Y188L 86;79;72;65;58;97 91;84;77;70;63;102 NNRTI 12 18 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Other major NRTIs resistance mutations detected included the multidrug resistance mutation T69D, the thymidine analogue mutation (TAM) T215F, and the non-TAMs K65R and Y115F (Table 3). 2017 Scientific reports Method HIV K65R;T215F;T69D;Y115F 159;133;91;168 163;140;95;173 NRTI 12 17 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Overall, M184V and K103N were the most prevalent NRTIs and NNRTIs transmitted or acquired DRMs, both for subjects infected with HIV-1 CRF02_AG and those infected with non-CRF02_AG subtypes (Table 3). 2017 Scientific reports Method HIV K103N;M184V 19;9 24;14 NNRTI;NRTI 59;49 65;54 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Six of the 11 subjects with major DRMs harbored viruses with the thymidine analogue mutations (TAMs) D67N, K70R, K219E/Q, and T215F (Tables 2 and 3). 2017 Scientific reports Method HIV D67N;K219E;K219Q;K70R;T215F 99;113;113;107;126 105;120;120;111;131 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Subject NA2CMR151 harbored viruses with both the Gag cleavage site mutations S373Q, T375G, I376V, G381S; the major NRTIs resistance mutations T69N, K70R, M184V, K219Q; the major NNRTIs resistance mutation Y181C, and the secondary NNRTIs resistance mutations A98G. 2017 Scientific reports Method HIV A98G;G381S;I376V;K219Q;K70R;M184V;S373Q;T375G;T69N;Y181C 258;98;91;161;148;154;77;84;142;205 262;103;96;166;152;159;82;89;146;210 NNRTI;NNRTI;NRTI;Gag 178;230;115;49 184;236;120;52 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Subject NA2CMR176 harbored viruses with both Gag cleavage site mutations A374T, T375G, I376V, G381S, the major NRTIs resistance mutations M184V, and the major NNRTIs resistance mutation Y188L. 2017 Scientific reports Method HIV A374T;G381S;I376V;M184V;T375G;Y188L 73;94;87;138;80;186 78;99;92;143;85;191 NNRTI;NRTI;Gag 159;111;45 165;116;48 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Subject NACMR050 harbored viruses with both Gag cleavage site mutation T375A and the secondary NNRTI resistance mutation V179E. 2017 Scientific reports Method HIV T375A;V179E 71;121 76;126 NNRTI;Gag 95;44 100;47 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. The R380G mutation was present only in subjects on ART. 2017 Scientific reports Method HIV R380G 4 9 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. These transmitted DRMs included major resistance mutations to NRTIs such as M184V, T69D, T215F, K65R, and Y115F; and major resistance mutations to non-Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NNRTIs) such as Y181C, K103N, P225H, V108I, K101E, Y188L, E138Q, and L100I (Table 2). 2017 Scientific reports Method HIV E138Q;K101E;K103N;K65R;L100I;M184V;P225H;T215F;T69D;V108I;Y115F;Y181C;Y188L 265;251;230;96;276;76;237;89;83;244;106;223;258 270;256;235;100;281;81;242;94;87;249;111;228;263 RT;NNRTI;NRTI 173;207;62 194;213;67 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Known and novel mutations were identified by comparing with NRTI-associated RNase H mutations previously identified from subtype B drug-resistance studies: K451R, D460N, L469F, T470N, T473A, N474A, Q475A, K476A/N, D488E, L491S, Q500A, Y501A/F, I505A, I506L, Q509L, K512Q, K527N, K530R, H539N, V518I, E529D, Q547K, D549N, A554S and K558E/R. 2017 Viruses Method HIV A554S;D460N;D488E;D549N;E529D;H539N;I505A;I506L;K451R;K476A;K476N;K512Q;K527N;K530R;K558E;K558R;L469F;L491S;N474A;Q475A;Q500A;Q509L;Q547K;T470N;T473A;V518I;Y501A;Y501F 321;163;214;314;300;286;244;251;156;205;205;265;272;279;331;331;170;221;191;198;228;258;307;177;184;293;235;235 326;168;219;319;305;291;249;256;161;212;212;270;277;284;338;338;175;226;196;203;233;263;312;182;189;298;242;242 NRTI 60 64 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. MDR769 L33F contains all mutations seen in MDR769 as well as the additional mutation L33F. 2015 Biochemistry and biophysics reports Method HIV L33F 85 89 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. MDR769 L33F is based on the previously studied multi-drug resistant variant 769, MDR769, which contains the mutations Q7K, L10I, M36V, M46L, I54V, I62V, L63P, A71V, V82T, I84V, L90M. 2015 Biochemistry and biophysics reports Method HIV A71V;I54V;I62V;I84V;L10I;L63P;L90M;M36V;M46L;Q7K;V82T 159;141;147;171;123;153;177;129;135;118;165 163;145;151;175;127;157;181;133;139;121;169 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Subsequent structures containing a PI were phased using the apo L33F structure as a search model. 2015 Biochemistry and biophysics reports Method HIV L33F 64 68 PI 35 37 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The structure of the apo L33F model was determined at a resolution of 1.50 A. 2015 Biochemistry and biophysics reports Method HIV L33F 25 29 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Specifically, we analyzed four LTNs including sequences with E138A (N = 22, 38, 50 and 38 for clusters 1, 2, 3, and 4, respectively) and one with K103N (N = 48) (Table 1). 2017 Genes Method HIV E138A;K103N 61;146 66;151 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. The study population corresponded to patients for whom viral sequences carried the most prevalent NNRTI resistance mutations (E138A and K103N) and were found to belong within monophyletic clusters (LTNs) as previously described. 2017 Genes Method HIV E138A;K103N 126;136 132;141 NNRTI 98 103 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. 26, September 2016), HIV-GRADE (http://www.hiv-grade.de, version January 16, 2017), and Rega (https://rega.kuleuven.be/cev/avd/software/rega-algorithm, v9.0.1, October 29, 2013) were considered: A49G, H51Y, V54I, L68IV, L74I, E92V, Q95K, H114Y, G118R, S119R, T124A, A128T, E138T, G140C, Y143AGS, P145S, Q146IKLPR, Q148EG, V151AIL, S153FY, N155ST, K156 N, E157Q, G163KR, T206S, S230GNR, D232N, V260I. 2017 Virology journal Method HIV A128T;A49G;D232N;E138T;E157Q;E92V;G118R;G140C;G163K;G163R;H114Y;H51Y;K156N;L68I;L68V;L74I;N155S;N155T;P145S;Q146I;Q146K;Q146L;Q148E;Q148G;Q95K;S119R;S153F;S153Y;S230G;S230N;S230R;T124A;T206S;V151A;V151I;V151L;V260I;V54I;Y143A;Y143G;Y143S 266;195;386;273;355;226;245;280;362;362;238;201;347;213;213;220;339;339;296;303;303;303;314;314;232;252;331;331;377;377;377;259;370;322;322;322;393;207;287;287;287 271;199;391;278;360;230;250;285;368;368;243;205;353;218;218;224;345;345;301;312;312;312;320;320;236;257;337;337;384;384;384;264;375;329;329;329;398;211;294;294;294 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. Major INSTI resistance mutations (T66I, E92Q, F121Y, Y143CHR, S147G, Q148HKR, N155H) that confer substantial phenotypic resistance to at least one of the currently approved INSTI as well as minor INSTI resistance mutations (T66AK, L74 M, E92G, T97A, E138AK, G140AS, R263K) that increase INSTI resistance and/or viral replication capacity were identified according to the IAS-list. 2017 Virology journal Method HIV E138A;E138K;E92G;E92Q;F121Y;G140A;G140S;L74M;N155H;Q148H;Q148K;Q148R;R263K;S147G;T66A;T66I;T66K;T97A;Y143C;Y143H;Y143R 250;250;238;40;46;258;258;231;78;69;69;69;266;62;224;34;224;244;53;53;53 256;256;242;44;51;264;264;236;83;76;76;76;271;67;229;38;229;248;60;60;60 INSTI;INSTI;INSTI;INSTI 6;173;196;287 11;178;201;292 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. Moreover, INSTI-selected mutations that were observed in vitro or in vivo were investigated: M50I, G59E, I60L, I72A, Q95T, L101IY, T112S, F121Y, T122I, T125A, E138D, Y143K, Q148N, M154I, I162M, G163E, Q177R, G193E, V201I, I203M, I204T. 2017 Virology journal Method HIV E138D;F121Y;G163E;G193E;G59E;I162M;I203M;I204T;I60L;I72A;L101I;L101Y;M154I;M50I;Q148N;Q177R;Q95T;T112S;T122I;T125A;V201I;Y143K 159;138;194;208;99;187;222;229;105;111;123;123;180;93;173;201;117;131;145;152;215;166 164;143;199;213;103;192;227;234;109;115;129;129;185;97;178;206;121;136;150;157;220;171 INSTI 10 15 29176596 Quenching protein dynamics interferes with HIV capsid maturation. A helical tube of mature-like CA(A92E)-SP1 NL4-3 was constructed by docking the MDFF-derived hexameric structure (PDB: 3J34), using Chimera, into the density of hexamer of tubes with (-8, 14) symmetry. 2017 Nature communications Method HIV A92E 33 37 SP1;Capsid 39;30 42;32 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Construction of an immature-like lattice of CA(A92E)-SP1 was performed by docking monomeric HIV-1 CTD (PDB: 2KOD) into the cryo-EM density derived from authentic virions (EMDB: 2706). 2017 Nature communications Method HIV A92E 47 51 SP1;Capsid 53;44 56;46 29176596 Quenching protein dynamics interferes with HIV capsid maturation. For CA CTD-SP1(T8I) mutant, 5860 frames were extracted from 0-15 mus MD trajectory. 2017 Nature communications Method HIV T8I 15 18 SP1;Capsid 11;4 14;6 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Full-length CA(A92E)-SP1 NL4-3 proteins (3.95 mg/ml) were diluted to 2.2 mg/ml in high salt buffer (1 M NaCl, 50 mM Tris pH 8.0) and incubated at 37 C for 1 h for tubular assembly. 2017 Nature communications Method HIV A92E 15 19 SP1;Capsid 21;12 24;14 29176596 Quenching protein dynamics interferes with HIV capsid maturation. MAS NMR spectra of tubular assemblies of CA NL4-3, CA-SP1(T8I) NL4-3, CA(A92E) NL4-3, and CA(A92E)-SP1 NL4-3 were acquired at 20.0 T, operating at Larmor frequencies of 850.4 MHz (1H), 213.8 MHz (13C), and 86.2 MHz (15N). 2017 Nature communications Method HIV A92E;A92E;T8I 73;93;58 77;97;61 SP1;SP1;Matrix;Capsid;Capsid;Capsid;Capsid 54;99;0;41;51;70;90 57;102;2;43;53;72;92 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Some experiments of CA-SP1(T8I) NL4-3 assemblies were performed at 14.1 T, with Larmor frequencies of 600.8 MHz (1H), 150.8 MHz (13C), and 60.8 MHz (15N). 2017 Nature communications Method HIV T8I 27 30 SP1;Capsid 23;20 26;22 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Spectra of CA-SP1(T8I) NL4-3 tubular assemblies were assigned by a sequential walk, using a combination of 2D CORD/direct-CORD, 2D/3D NCACX, 2D/3D NCOCX, 3D CONCA, and 2D J-INADEQUATE experiments. 2017 Nature communications Method HIV T8I 18 21 SP1;Capsid 14;11 17;13 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The CA(A92E) mutation was used since in previous work we showed that the A to E change prevents the tubes from aggregating, resulting in higher resolution cryo-EM data than for the WT CA, and attenuates the CypA loop dynamics. 2017 Nature communications Method HIV A92E 7 11 Capsid;Capsid 4;184 6;186 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The following sequence variants/mutants were studied: WT CA NL4-3, CA(A92E) NL4-3, WT CA HXB2, CA(A92E)-SP1 NL4-3, WT CA-SP1 HXB2, and CA-SP1(T8I) NL4-3; where (A92E) and (T8I) designate mutations in the CA and SP1 regions, respectively; NL4-3 and HXB2 refer to strain variants. 2017 Nature communications Method HIV A92E;A92E;A92E;T8I;T8I 70;98;161;172;142 74;102;165;175;145 SP1;SP1;SP1;SP1;Capsid;Capsid;Capsid;Capsid;Capsid;Capsid;Capsid 104;121;138;211;57;67;86;95;118;135;204 107;124;141;214;59;69;88;97;120;137;206 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The temperature rung and associated weights were calculated using the Park method, and are presented in Supplementary Tables 4 and 5 for WT and the T8I mutant, respectively. 2017 Nature communications Method HIV T8I 148 151 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Tubular assemblies of CA and CA(A92E)-SP1 NL4-3 and WT CA-SP1 HXB2 were prepared from 32 mg/ml protein solutions in 25 mM phosphate buffer (pH 5.5), containing 1 M NaCl. 2017 Nature communications Method HIV A92E 32 36 SP1;SP1;Capsid;Capsid;Capsid 38;58;22;29;55 41;61;24;31;57 29176596 Quenching protein dynamics interferes with HIV capsid maturation. WT CA NL4-3 and CA-SP1(T8I) NL4-3 tubes were pre-assembled from 26 mg/ml protein solutions in 25 mM phosphate buffer (pH 5.5), containing 2.4 M NaCl, followed by incubation at 37 C for 1 h and 4 C overnight. 2017 Nature communications Method HIV T8I 23 26 SP1;Capsid;Capsid 19;3;16 22;5;18 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The following sequence changes to the SOSIP.664 introduce additional stability: E64K plus A316W to generate SOSIP.v4.1 and E64K plus A316W and the A73C-A561C intersubunit disulfide bond to make SOSIP.v5.2. 2018 The Journal of biological chemistry Method HIV A316W;A316W;A561C;A73C;E64K;E64K 90;133;152;147;80;123 95;138;157;151;84;127 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The V3 peptide was based on the sequence of the BG505 SOSIP immunogen, either unmodified (CTRPNNNTRKSIRIGPQAFYATGDIIGDIRQAHC) or including the S306L, R308L, and A316W changes highlighted in bold (CTRPNNNTRKLILIGPQWFYATGDIIGDIRQAHC). 2018 The Journal of biological chemistry Method HIV A316W;R308L;S306L 161;150;143 166;155;148 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We used BG505 SOSIP.D7324 and SOSIP.v5.2 S306L/R308L trimers (1 mug/ml) to quantify trimer binding titers in rabbit sera and BG505 V3 peptide to quantify anti-V3 titers (see below). 2018 The Journal of biological chemistry Method HIV R308L;S306L 47;41 52;46 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. Synthetic ligation products purchased from Integrated DNA Technologies (IDT) were run in adjacent lanes for a size comparison (WT: 5'-dig-AGACATAGTTATCTATCAATACATGGATGATTTGTATGTAGGATC-bio-3'; M184V: 5'-FAM- AGACATAGTTATCTATCAATACGTGGATGATTTGTATGTAGGATC-bio-3'). 2018 Analytical biochemistry Method HIV M184V 192 197 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. The selected primers amplify a 338-base-pair region (nt 2810 to 3147) of the pol gene that contains the resistance mutations M184V, K103N, Y181C, and V106M. 2018 Analytical biochemistry Method HIV K103N;M184V;V106M;Y181C 132;125;150;139 137;130;155;144 Pol 77 80 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. To assess the specificity of the integrated assay, samples containing 105 copies of wild type only DNA or M184V mutant only DNA were added as input to the RPA reaction and run through the integrated assay as described above. 2018 Analytical biochemistry Method HIV M184V 106 111 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. Two separate stocks were used, one encoding the sequence for wild type HIV-1 and other encoding the sequence that includes the M184V drug resistance mutation. 2018 Analytical biochemistry Method HIV M184V 127 132 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Additionally, if the M50I/R263K mutation was present, we termed it as intermediate resistance to BIC. 2018 AIDS (London, England) Method HIV M50I;R263K 21;26 25;31 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. For BIC, the presence of E138K/Q148R, G140S/Q148R or N155H/Q148R was interpreted as high level resistance. 2018 AIDS (London, England) Method HIV E138K;G140S;N155H;Q148R;Q148R;Q148R 25;38;53;31;44;59 30;43;58;36;49;64 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. For CAB, the presence of E138A/Q148R, E138K/Q148K, E138K/Q148R, G140C/Q148R, G140S/Q148R, or Q148R/N155H was interpreted as high-level resistance. 2018 AIDS (London, England) Method HIV E138A;E138K;E138K;G140C;G140S;N155H;Q148K;Q148R;Q148R;Q148R;Q148R;Q148R 25;38;51;64;77;99;44;31;57;70;83;93 30;43;56;69;82;104;49;36;62;75;88;98 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. M50I was present in seven of the sequences from the HIV-1B (n=3) and the HIV-1C (n=4) strains. 2018 AIDS (London, England) Method HIV M50I 0 4 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. PCR-based mutagenesis was used to introduce Ala substitutions at either one or both of two Asn residues (N65A, N92A, and N65,92A) that are targets for N-linked glycosylation. 2018 Viruses Method HIV N65A;N92A 105;111 109;115 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Heterodimeric (p66/p51) wild-type (WT) RTs of HIV-1 group M strain BH10 (HIV-1BH10), HIV-1 group O strain ESP49 (HIV-1ESP49) and HIV-1ESP49 mutants K65R and K65R/V75I (O_K65R and O_K65R/V75I, respectively) were obtained as previously described. 2018 Scientific reports Method HIV K65R;K65R;K65R;K65R;V75I;V75I 148;157;170;181;162;186 152;161;174;185;166;190 RT 39 42 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. MLV and AMV RTs were obtained from Promega (catalogue #M170A and #M5101, respectively). 2018 Scientific reports Method HIV M170A 55 60 RT 12 15 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. The purified RNA was used as template in reverse transcription reactions carried out with WT AMV, MLV, HIV-1BH10 and HIV-1ESP49 RTs, and mutant O_K65R and O_K65R/V75I RTs. 2018 Scientific reports Method HIV K65R;K65R;V75I 146;157;162 150;161;166 RT;RT;RT 41;128;167 62;131;170 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. HEK293T cells transfected with L-MBP-p6*-F56C-PRL63P-HA encoding plasmid grown in 3 x T175 flasks were collected by trypsin-EDTA treatment followed by a brief centrifugation (1000 x g for 5 min). 2018 PloS one Method HIV F56C 41 45 Gag;PR 37;46 39;48 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. After the 2 days of transfection, cells were cross-linked with 1% paraformaldehyde for 10 min, followed by quenching with 0.125 M glycine for 5 min at room temperature. 2018 Retrovirology Method HIV G5M 128 143 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Briefly, HEK293T cells were co-transfected with pLenti6, pLP1-D64A, pLP2, and pLP-VSV-G using Lipofectamine 2000 transfection reagent. 2018 Retrovirology Method HIV D64A 62 66 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. For FRAP assay, newly established cell lines: Mit-23 with H2B(Wt)-GFP or H2B(K120R)-GFP, HT1080vRxt-Vpr-Wt or -Q65R with H2B(Wt)-GFP, in which pEF-Bos-H2B-GFP was stably transduced to Mit-23 or HT1080vRxt-Vpr, were treated with Dox (3 mug/ml) for 1.5 days. 2018 Retrovirology Method HIV K120R;Q65R 77;111 82;115 Vpr;Vpr 100;205 103;208 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Antiviral assays (p24 assay) using wild-type HIV-1 (HIV-1WT) and replicable HIV-1 variants (HIV-1Q151M, HIV-1Q151M/Y115F/F116Y, and HIV-1Q151M/I63V/L74V) were also conducted as previously described. 2018 Scientific reports Method HIV F116Y;L74V;Y115F 121;148;115 126;152;120 p24 18 21 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. For preparation of the RTQ151M:DNA:dGTP and RTQ151M:DNA:ETV-TP ternary complex, the crystals were further soaked briefly in the same cryoprotectant solution supplemented with 2.4 mM dGTP/ETV-TP. 2018 Scientific reports Method HIV Q151M;Q151M 25;46 30;51 RT;RT 23;44 25;46 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Recombinant HIV-1 RTWT and RTQ151M were overexpressed by E. 2018 Scientific reports Method HIV Q151M 29 34 RT 27 29 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. RTQ151M:DNA complex formation. 2018 Scientific reports Method HIV Q151M 2 7 RT 0 2 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The atomic coordinates and structure factor amplitudes of the RTQ151M:DNA, RTQ151M:DNA:ETV-TP, and RTQ151M:DNA:dGTP complexes have been deposited in the RCSB Protein Data Bank (http://www.rcsb.org) under accession codes 5XN0, 5XN1, and 5XN2, respectively. 2018 Scientific reports Method HIV Q151M;Q151M;Q151M 64;77;101 69;82;106 RT;RT;RT 62;75;99 64;77;101 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The DNA and purified RTQ151M were mixed and incubated overnight at 4 C. 2018 Scientific reports Method HIV Q151M 23 28 RT 21 23 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The previously established 38-mer hairpin DNA aptamer was employed for the structural study of the RTQ151M:DNA:dGTP/ETV-TP ternary complex with 3 base substitutions to accommodate dGTP and ETV-TP at the N-site. 2018 Scientific reports Method HIV Q151M 101 106 RT 99 101 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The RT activity of HIV-1 RTWT and RTQ151M was determined using ELISA and PCR methods. 2018 Scientific reports Method HIV Q151M 36 41 RT;RT 4;34 6;36 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Mechanism of darunavir (DRV)'s high genetic barrier to HIV-1 resistance: a key V32I substitution in protease rarely occurs, but once it occurs, it predisposes HIV-1 to develop DRV resistance. 2018 mBio Method HIV V32I 79 83 PR 100 108 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Additional subtype C resistance-associated C-terminal mutations/polymorphisms observed were G335D (86%), A371V (19%) and A376S (12%). 2018 Antiviral chemistry & chemotherapy Method HIV A371V;A376S;G335D 105;121;92 110;126;97 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. From the treatment-naive group, eight individuals had G335D and one individual had A376S. 2018 Antiviral chemistry & chemotherapy Method HIV A376S;G335D 83;54 88;59 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. In total, 94 of 100 samples from patients failing ARV treatment also carried HIV-1 NRTI resistane mutations including M184V (82%), K65R (35%), L74I (19%), M41L (17%) or D67N (17%). 2018 Antiviral chemistry & chemotherapy Method HIV D67N;K65R;L74I;M184V;M41L 169;131;143;118;155 173;135;147;123;159 NRTI 83 87 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Plasma samples contained a median of 3 [Q1-Q3: 2-4] NNRTI-associated drug resistance mutations which included A98G, L100I, K101E/H, K103N/S, V106M, V108I, E138A/K, V179D/E Y181C, Y188L/C, G190A, H221Y, P225H, F227L, and M230L. 2018 Antiviral chemistry & chemotherapy Method HIV A98G;E138A;E138K;F227L;G190A;H221Y;K101E;K101H;K103N;K103S;L100I;M230L;P225H;V106M;V108I;V179D;V179E;Y181C;Y188C;Y188L 110;155;155;209;188;195;123;123;132;132;116;220;202;141;148;164;164;172;179;179 114;162;162;214;193;200;130;130;139;139;121;225;207;146;153;171;171;177;186;186 NNRTI 52 57 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Resistance mutations in the connection and RNAse H domains of RT spanning amino acids 320-560 included Y318F (3%) and N348I (14%). 2018 Antiviral chemistry & chemotherapy Method HIV N348I;Y318F 118;103 123;108 RT 62 64 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. The most frequent EFV and NVP resistance mutations were K103N in 55 of 100 samples (55%), V106M (44%) and G190A (26%). 2018 Antiviral chemistry & chemotherapy Method HIV G190A;K103N;V106M 106;56;90 111;61;95 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. After one mixture (M184M/V) was identified in a recipient partner (PIC 90629), specimens from two later time points were evaluated to assess the intrahost dynamics of the M184V mutation over time and determine whether this mixture arose from a single transmitted variant and evolution in the recipient or from initial infection by two transmitted variants. 2018 PLoS medicine Method HIV M184M;M184V;M184V 19;19;171 26;26;176 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. After mutagenesis of the pGSHIV-1NL4.3 shuttle vector, the pGCHIV-1NL4.3 shuttle vector and HIV-1NL4.3 were digested with EcoRI and SphI and the mutated shuttle fragment was ligated into digested HIV-1NL4.3 to construct HIV-1NL4.3-pol-E297R, -E298R, and -E300R. 2018 mBio Method HIV E297R;E298R;E300R 235;243;255 240;248;260 Pol 231 234 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Biosensors with eEF1A1 bound were incubated in 90 nM WT or E300R RTp51/p66 heterodimer purified from E. 2018 mBio Method HIV E300R 59 64 RT 65 67 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Purification of WT and E300R mutant RTp51/p66 heterodimer from E. 2018 mBio Method HIV E300R 23 28 RT 36 38 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E300R mutation was introduced into p6HRT-PROT by inverse PCR with Phusion polymerase (New England Biolabs), and the mutation was confirmed by sequencing. 2018 mBio Method HIV E300R 4 9 Pol 78 88 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The primers used to generate p6HRT-PROT-E300R were as follows: forward, 5'-CGTCTAGAACTGGCAGAAAACAGA-3'; reverse, 5'-TGCTTCTTCTGTTAGTGGTATTACTT-3'. 2018 mBio Method HIV E300R 40 45 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The WT or E300R mutant p6HRT-PROT expression vector and the pDM1.1 vector were cotransformed into E. 2018 mBio Method HIV E300R 10 15 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. WT or E300R HIV-1 virions (~20 ng) were used in an ERT assay as previously described. 2018 mBio Method HIV E300R 6 11 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. HIV-1 (IIIB, K103 N/Y181C (RES056), F227L/V106A, L100I, K103 N, E138K, Y181C, and Y188L) or HIV-2 (ROD) stock (50 muL at 100-300 CCID50) (50% cell culture infectious dose) or culture medium was added to either the infected or mock-infected wells of the microtiter tray. 2018 European journal of medicinal chemistry Method HIV E138K;F227L;K103N;L100I;V106A;Y181C;Y181C;Y188L 64;36;56;49;42;20;71;82 69;41;62;54;47;25;76;87 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Mass spectra were taken on a LC Autosampler Device: Standard G1313A instrument. 2018 European journal of medicinal chemistry Method HIV G1313A 61 67 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. The two representative compounds 3b8 and 3b9 were docked into the NNRTIs binding pocket in WT (PDB code: 3MEC, crystal complex with ETR) and E138K mutated (PDB code: 2HNZ, crystal complex with PETT-2 as a phenethylthiazolylthiourea derivative) RT using the Surflex-Dock of SYBYL-X 2.0. 2018 European journal of medicinal chemistry Method HIV E138K 141 146 NNRTI;RT 66;244 72;246 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. cluster 3), the number of mutant structures in cluster 3 with the mutation L76M divided by the number of mutant structures in cluster 3. 2018 Scientific reports Method HIV L76M 75 79 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. L76M) and a given cluster (e.g. 2018 Scientific reports Method HIV L76M 0 4 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. For N74D/CA mutant, the time of uncoating at the NE was measured as the interval between single particle arrival/docking at the nuclear membrane and loss of CypA-DsRed. 2018 Cell host & microbe Method HIV N74D 4 8 Capsid 9 11 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. For the N74D/CA mutant, IN complexes that remained associated with the NE after uncoating and subsequent disappearance of a fraction of these complexes were quantified. 2018 Cell host & microbe Method HIV N74D 8 12 IN;Capsid 24;13 26;15 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. The pHIV-eGFP (NL4.3 R-E- eGFP) and N74D-eGFP plasmids were a gift from Dr. 2018 Cell host & microbe Method HIV N74D 36 40 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. The pR9DeltaEnv vector containing the WT CA or CA mutations E45A, and K203A was described previously. 2018 Cell host & microbe Method HIV E45A;K203A 60;70 64;75 Capsid;Capsid 41;47 43;49 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. VSV-G pseudotyped pHIV-eGFPDeltaEnv particles containing WT/CA or the N74D/CA mutant were co-labeled with INsfGFP and CypA-DsRed and used to infect the cells at MOI of 0.2. 2018 Cell host & microbe Method HIV N74D 70 74 Capsid;Capsid 60;75 62;77 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Few data are available before this period, as resistance testing was not widely available, with no recorded observations of either Q151M or T69i mutations. 2018 AIDS research and therapy Method HIV Q151M 131 136 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Multivariable Cox regression was used to investigate the factors associated with successful viral suppression following detection of either the Q151M or T69i mutation. 2018 AIDS research and therapy Method HIV Q151M 144 149 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Presence or absence of the K65R mutation was also included as a predictor, and analyses were also conducted including the respective accessory mutations for Q151M and T69i. 2018 AIDS research and therapy Method HIV K65R;Q151M 27;157 31;162 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. To investigate the association between Q151M and 69i and mortality, we carried out a matched cohort analysis of comparable patients in whom ART data were available. 2018 AIDS research and therapy Method HIV Q151M 39 44 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. 293T cells were transfected with pAd.CMV link 1 Flag-Tat WT, Tat S16A or Tat S46A mutant expressing plasmids using Lipofectamine and Plus reagents (Life Technologies). 2018 Retrovirology Method HIV S16A;S46A 65;77 69;81 Tat;Tat;Tat 53;61;73 56;64;76 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. CEM T cells were infected with pseudotyped viruses pNL4-3.Luc.R-E with WT Tat and Tat S16A, S16E, S46A and S46E mutants. 2018 Retrovirology Method HIV S16A;S16E;S46A;S46E 86;92;98;107 90;96;102;111 Tat;Tat 74;82 77;85 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. pAd.CMV link 1 Tat plasmids expressing WT Tat, TatS16A, Tat S16D, Tat S46A and Tat S46D were generated as previously described. 2018 Retrovirology Method HIV S16D;S46A;S46D 60;70;83 64;74;87 Tat;Tat;Tat;Tat;Tat;Tat 15;42;47;56;66;79 18;45;50;59;69;82 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. To analyze Tat ubiquitination in vivo, 293T cells grown in 6-well plates were co-transfected with 1 mug/well of pCI-His-hUbi plasmid (Addgene) and 1.5 mug/well of WT Flag-Tat, Flag-Tat S16A, Flag-Tat S16D, Flag-Tat S46A, Flag-Tat S46D or Flag-Tat K71A plasmid using Lipofectamine as described above. 2018 Retrovirology Method HIV K71A;S16A;S16D;S46A;S46D 247;185;200;215;230 251;189;204;219;234 Tat;Tat;Tat;Tat;Tat;Tat;Tat 11;171;181;196;211;226;243 14;174;184;199;214;229;246 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. To mutate Tat lysine 71 which is the subject of ubiquitination, an alanine mutant (K71A) was generated in pCMV Link 1 Tat vector using TCAGACTCATCAGGCTTCTCTATCAGCGCAATCCCTACCC (forward) and GGGTAGGGATTGCGCTGATAGAGAAGCCTGATGAGTCTGA (reverse) primers following the above mentioned procedure. 2018 Retrovirology Method HIV K71A 83 87 Tat;Tat 10;118 13;121 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Whole cell lysates from 293T cells grown in 6-well plates and transfected with 2 mug/well of plasmids expressing WT Flag-Tat, Flag-Tat S16A or Flag-Tat S46A were added to the beads in TAK buffer (50 mM Tris-HCl pH 8.0, 5 mM MgCl2, 5 mM MnCl2, 10 muM ZnSO4, 1 mM DTT, 100 mM NaCl) and rotated for 2 h at 4 C. 2018 Retrovirology Method HIV S16A;S46A 135;152 139;156 Tat;Tat;Tat 121;131;148 124;134;151 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. A subset of the NRTI-associated SDRMs were classified as thymidine analogue mutations (TAMs) including M41L, D67N/G, K70R, L210W, T215Y/F, K219Q/E/R/N, and the T215 revertants T215C/D/E/I/S/V (which evolve from T215F/Y in the absence of selective drug pressure). 2019 Clinical infectious diseases Method HIV D67G;D67N;K219E;K219N;K219Q;K219R;K70R;L210W;M41L;T215C;T215D;T215E;T215F;T215F;T215I;T215S;T215V;T215Y;T215Y 109;109;139;139;139;139;117;123;103;176;176;176;130;211;176;176;176;130;211 115;115;150;150;150;150;121;128;107;191;191;191;137;218;191;191;191;137;218 NRTI 16 20 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. Several additional DRMs not on the SDRM list were analyzed including (1) the primarily tenofovir disoproxil fumarate (TDF)-selected DRMs A62V, K65N, and K70G/N/Q/S/T and (2) the primarily rilpivirine (RPV)-selected DRMs E138A/G/K/Q, of which E138A is polymorphic, occurring in 1%-4% of viruses from ART-naive individuals. 2019 Clinical infectious diseases Method HIV A62V;E138A;E138A;E138G;E138K;E138Q;K65N;K70G;K70N;K70Q;K70S;K70T 137;220;242;220;220;220;143;153;153;153;153;153 141;231;247;231;231;231;147;165;165;165;165;165 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Secondary objectives were to compare time to virological blips between the 2 groups and time to virological failure between the DT group (overall and with M184V+) and the bPI monotherapy group. 2018 Open forum infectious diseases Method HIV M184V 155 160 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The occurrence of M184V was assessed using historical genotypic resistance tests (hGRTs); that is, any detection of this mutation in any previous resistance test was scored as positive. 2018 Open forum infectious diseases Method HIV M184V 18 23 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The primary objective of the study was to compare time to virological failure and time to treatment discontinuation between the M184V- and M184V+ groups. 2018 Open forum infectious diseases Method HIV M184V;M184V 128;139 133;144 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. We performed sensitivity analyses considering M184V only in the last available genotypic resistance tests and a different definition of virological failure (HIV-RNA >50 copies/mL in 2 consecutive determinations or a single determination >=1000 copies/mL) and of virological blips (single HIV-RNA between 51 and 999 copies/mL not confirmed at the subsequent determination). 2018 Open forum infectious diseases Method HIV M184V 46 51 30056211 Binding of host factors to stabilized HIV-1 capsid tubes. Point mutations, A14C and E45C were introduced using the QuikChange II site-directed mutagenesis kit (Stratagene) according to the manufacturer's instructions. 2018 Virology Method HIV A14C;E45C 17;26 21;30 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The parental NFL contains a proline substitution at residue 559 (I559P) to facilitate trimer formation. 2018 Frontiers in immunology Method HIV I559P 65 70 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. To construct pAIP-Vpr WT or pAIP-Vpr H71R, a DNA fragment encoding Vpr WT or H71R was amplified from pcDNA3-HA-Vpr WT or pcDNA3-HA-Vpr H71R by TKs Gflex DNA polymerase (TAKARA) and the following pair of primers: 5'-TCTCTCCCCATCTAGATGGAACAAGCCCCAGAAGAC-3' (Forward), 5'-GCGTTTAAACGGATCCTAGGATCTACTGGCTCCATT-3' (Reverse). 2018 Nucleic acids research Method HIV H71R;H71R;H71R 37;77;135 41;81;139 Pol;Vpr;Vpr;Vpr;Vpr;Vpr 157;18;33;67;111;131 167;21;36;70;114;134 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. To construct pcDNA3-HA-Vpr WT, pcDNA3-HA-Vpr H71R, or pEGFP-Vpr, a DNA fragment encoding HIV-1 Vpr was amplified from pCMX Vpr96 by PCR using KOD-Plus DNA polymerase and the following pairs of primers: HA-Vpr WT, 5'-CGGGATCCAAGATGGAACAAGCCCCAGAAG-3' (Forward), 5'-CCGGCGGCCGCCTAGGATCTACTGGCTCCA-3' (Reverse); HA-Vpr H71K, 5'-CGGGATCCAAGATGGAACAAGCCCCAGAAG-3' (Forward), 5'-CCG GCGGCCGCCTAGGATCTACTGGCTCCATTTCTTGCTCTCCTCTGTCGAGTAACGCCTATTCTGCTATGTCGACACCCAATTCTGAAACGGATAAACA-3' (Reverse); EGFP-Vpr, 5'-CGCTCGAGAAGATGGAACAAGCCCCAGAAG-3' (Forward), 5'-CGGGATCCCTAGGATCTACTGGCTCCATTT-3' (Reverse). 2018 Nucleic acids research Method HIV H71K;H71R 316;45 320;49 Pol;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr 155;23;41;60;95;123;205;312;494 165;26;44;63;98;126;208;315;497 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Clinical plasma samples were also obtained from treatment-naive persons harboring the WT (n = 5) or E157Q (n = 5) substitution in integrase. 2018 Retrovirology Method HIV E157Q 100 105 IN 130 139 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Human SERINC5 mutants L350A and I352A, as well as frog and zebrafish orthologs and frog/human SERINC5 chimeras were described before. 2018 PLoS pathogens Method HIV I352A;L350A 32;22 37;27 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Mutant Nef variants (SIVcol Y86F, Y87F Nef) were generated by mutating TAT (Tyr86) to TTC (Phe) and TAC (Tyr87) to TTC (Phe). 2018 PLoS pathogens Method HIV Y86F;Y87F 28;34 32;38 Nef;Nef;Tat 7;39;71 10;42;74 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Recombinant HIV-1 clones (HIV-1K65R, HIV-1A114V, HIV-1Y115A, HIV-1F160A, HIV-1M184V HIV-1D185A HIV-1T215F HIV-1D67del/T69G/K70R/L74I/V75T [HIV-167-75], and HIV-1D67del/T69G/K70R/L74I/V757T/M184V/T215F [HIV-167-75,184,215]) were propagated using HIV-1NL4-3-based infectious clones generated using QuikChange II XL Site-Directed Mutagenesis Kit (Agilent Technologies, Santa Clara, CA). 2018 Cell chemical biology Method HIV K70R;K70R;L74I;L74I;M184V;T215F;T69G;T69G;V757T;V75T 123;173;128;178;189;195;118;168;183;133 127;177;132;182;194;200;122;172;188;137 Capsid 379 381 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. PRWT and PRL76V proteins contain optimizing mutations Q7K/L33I/L63I to reduce autoproteolysis and C67A/C95A to prevent thiol bond formation. 2018 ACS omega Method HIV L33I;L63I;Q7K;C67A;C95A 58;63;54;98;103 62;67;57;102;107 PR 9 11 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Crystals of the P122A and I124A CA grew at 18 C in hanging drops containing 5 mg/ml of protein, 6% to 9% polyethylene glycol (PEG) 3350, 2% to 6% glycerol, sodium iodide, and sodium cacodylate. 2018 mBio Method HIV I124A;P122A 26;16 31;21 Capsid 32 34 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. For collection of immature HIV-1 WT and PPIP mutant particles, molecular clones bearing the Asp25Asn mutation that inactivates PR were used. 2018 mBio Method HIV D25N 92 100 Asp;PR 92;127 95;129 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. For expression and purification of CA proteins, P122A and I124A mutations were introduced into the pET11a HIV-1 CA Escherichia coli expression plasmid kindly provided by C. 2018 mBio Method HIV I124A;P122A 58;48 63;53 Capsid;Capsid 35;112 37;114 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A and I124A CA were cloned without fusion tags in the pET11a plasmid. 2018 mBio Method HIV I124A;P122A 10;0 15;5 Capsid 16 18 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A, PDB ID 6AXR; I124A, PDB ID 6AXW. 2018 mBio Method HIV I124A;P122A 20;0 25;5 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. WT and I124A virions and PR- derivatives of WT, P122A, I124A, and T58S/T107I/P122A virions were imaged by cryo-ET as described previously. 2018 mBio Method HIV P122A;T107I;T58S;I124A;I124A;P122A 77;71;66;7;55;48 82;76;70;12;60;53 PR 25 27 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. A Q7K mutation was included to prevent autoproteolysis. 2019 ACS infectious diseases Method HIV Q7K 2 5 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. In short, the protease variant genes (I50V, V82I, I84V) were constructed using QuikChange site-directed mutagenesis (Genewiz) onto NL4-3 WT protease on a pET11a plasmid with codon optimization for protein expression in Escherichia coli. 2019 ACS infectious diseases Method HIV I50V;I84V;V82I 38;50;44 42;54;48 PR;PR 14;140 22;148 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. TAMs comprised the RT mutations M41L, D67N/G/E, K70R, L210W, T215Y/F/rev and K219Q/E/N/R; T215rev comprised any change from T215 other than T215Y and T215F. 2019 The Journal of antimicrobial chemotherapy Method HIV D67E;D67G;D67N;K219E;K219N;K219Q;K219R;K70R;L210W;M41L;T215F;T215F;T215Y;T215Y 38;38;38;77;77;77;77;48;54;32;61;150;61;140 46;46;46;88;88;88;88;52;59;36;72;155;72;145 Rev;RT 69;19 72;21 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. TDR mutations were defined according to the WHO 2009 surveillance list, with the addition of any unlisted change at position T215 and the non-polymorphic RT mutation E138K. 2019 The Journal of antimicrobial chemotherapy Method HIV E138K 166 171 RT 154 156 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. The remaining 311 (4.5%) subjects were excluded owing to the presence of other forms of TDR, most commonly the NNRTI mutation K103N. 2019 The Journal of antimicrobial chemotherapy Method HIV K103N 126 131 NNRTI 111 116 30557314 The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. The CAP256 SU gp160 sequence was modified as follows (Fig 1A): the native leader sequence was removed, the furin cleavage site was replaced with a flexible linker sequence (FL), and an I548P mutation equivalent to the I559P in the SOSIP trimers was introduced to promote trimerisation of gp41. 2018 PloS one Method HIV I548P;I559P 185;218 190;223 gp160;gp41;Capsid 14;288;4 19;292;6 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. A G1313A standard LC autosampler (Agilent) was used to collect samples for measurement of mass spectra. 2019 Journal of medicinal chemistry Method HIV G1313A 2 8 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. 1A: the native leader (signal peptide [SP]) was removed and replaced with the human tissue plasminogen activator (TPA) leader sequence, the furin cleavage site was replaced with a flexible linker sequence (FL), and an I548P mutation equivalent to the I559P in the SOSIP trimers was introduced to improve the trimerization of gp41. 2019 Journal of virology Method HIV I548P;I559P 218;251 223;256 gp41 325 329 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. A transfer vector was created in which, in between flanking sequences of the MVA G1L-I8R locus, a selection cassette containing eGFP under the control of the VACV p7.5 promoter, K1L under the control of the VACV pSS promoter, and TPA-gp150-FL-IP under the control of the VACV mH5 promoter were inserted to form the plasmid Shuttle and Selection for Pox Expression (pSSPEx) CAP256 gp150-FL-IP. 2019 Journal of virology Method HIV I8R;K1L 85;178 88;181 Capsid 373 375 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. Serum from selected animals and time points were also tested against CAP256 SU K169E, BG505 N332_CAP256 V1V2-loop, CAP84_CAP256 V1V2-loop and a Tier 2 global panel (X1632, 398F1, 25710, BJX2000, CE0217, CE1176, CH119, CNE8, CNE55, TRO.11, X2278, and 246F3). 2019 Journal of virology Method HIV K169E 79 84 Capsid 69 71 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. This plasmid allows for positive selection of integration into MVA via K1L selection in RK13 cells and identification of recombinant virus by eGFP expression. 2019 Journal of virology Method HIV K1L 71 74 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. Three days after infection and transfection, cells were freeze-thawed and the viral lysate was passaged in RK13 cells, a cell line permissive to MVA in the presence of K1L expression. 2019 Journal of virology Method HIV K1L 168 171 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Cells were maintained as described in the section on the reverse transcriptase assay procedure and were infected using 2 x 105 cpm reverse transcriptase units per well either with single-virus stock or a combination of wild-type and variant viruses (V142I Vif mutant virus or cloned RN18 analog-resistant virus). 2019 mBio Method HIV V142I 250 256 RT;RT;Vif 57;131;256 78;152;259 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. C20 microglia were exposed for 24 h, to equivalent inputs of HeLa cell media containing Tat protein (Tat-B*, Tat-B* R57S, Tat-C or Tat-C S57R or empty vector) as described above for cytokine expression. 2019 Scientific reports Method HIV R57S;S57R 116;137 120;141 Tat;Tat;Tat;Tat;Tat 88;101;109;122;131 91;104;112;125;134 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Furthermore, to endow the Tat-B proteins with the same antibody epitope as Tat-C, to facilitate equal antibody recognition during ELISA, mutations were created in plasmids coding for Tat-B-WT and Tat-B-R57S at amino acid residues 7 (Arg to Asn) and 12 (Lys to Asn) respectively using site directed mutagenesis (5'GCCATGGAGCCAGTAGATCCTAACCTAGAGCCCTGGAATCATCCAGGAAGCCAGCC3'). 2019 Scientific reports Method HIV K12N;R57S;R7N 249;202;230 264;206;244 Tat;Tat;Tat;Tat 26;75;183;196 29;78;186;199 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Site-directed mutagenesis was used to create codon 57 substitutions in each tat gene, to express Tat-B-R57S (5'-GGAGACAGCGACGAAGCACTCCTCAAGACAGTC3') or Tat-C-S57R (5'AGACAGCGACGAAGAGCTCCTCCAAGCAG3'). 2019 Scientific reports Method HIV R57S;S57R 103;158 107;162 Tat;Tat;Tat 76;97;152 79;100;155 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Two other substitutions, a W11A (5'-TCCTAGACTAGAGCCCGCGAAGCATCCAGGAAGC3') and a triple alanine substitution in residues 49-RKK-51 (5'AGGCTTAGGCATCTCCTATGGCGCGGCGGCGCGGAGACAGCGACGAAGAACT-3') were introduced in the HIV-1B tat gene. 2019 Scientific reports Method HIV W11A 27 31 Tat 220 223 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Double (H547A/Y88F) and triple (H547A/Y88F/K92M) mutations were generated based on the wild type hDAT (WT hDAT) sequence (NCBI, cDNA clone MGC: 164608 IMAGE: 40146999) by site-directed mutagenesis. 2019 Scientific reports Method HIV H547A;K92M;Y88F;H547A;Y88F 32;43;38;8;14 37;47;42;13;18 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Intact PC12 cells transfected with WT or Y88F/H547A were preincubated with or without PMA for 30 min at 37 C followed by additional 8 min incubation with six concentrations of mixed [3H]DA as described above. 2019 Scientific reports Method HIV H547A;Y88F 46;41 51;45 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Single mutants, Y88F, K92M, and H547A, are expected to abolish hydrogen bonds between hDAT and Tat. 2019 Scientific reports Method HIV H547A;K92M;Y88F 32;22;16 37;26;20 Tat 95 98 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. The cell suspensions from WT hDAT or Y88F/H547A mutant were then preincubated with or without recombinant Tat1-86 (rTat1-86, 140 nM, final concentration, Diatheva, Fano, Italy) at room temperature for 20 min followed by additional 8 min incubation with a mixed [3H]DA uptake (0.05 microM, final concentration). 2019 Scientific reports Method HIV H547A;Y88F 42;37 47;41 Tat 106 109 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. To confirm whether Y88F/H547A-induced increase in Vmax was dependent on PKC regulatory mechanism, the Vmax of [3H]DA uptake was measured in the presence or absence of 1 microM PMA, a PKC activator (Tocris, Bristol, UK) as the previous reports. 2019 Scientific reports Method HIV H547A;Y88F 24;19 29;23 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. To determine the effect of amphetamine (AMPH) on Y88F/H547A-mediated transporter conformational transitions, Vmax or Km of [3H]DA uptake in WT and Y88F/H547A was determined in the presence or absence of 1 microM AMPH (Sigma-Aldrich, St. 2019 Scientific reports Method HIV H547A;H547A;Y88F;Y88F 54;152;49;147 59;157;53;151 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. All had consented to continued participation in the ACTG Longitudinal Linked Randomized Trials (ALLRT) protocol, and 28 were successfully suppressed on LPV/r regimens after viral failure with K103N. 2019 Open forum infectious diseases Method HIV K103N 192 197 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Nucleoside reverse-transcriptase inhibitor DRMs included M41I/L, D67N/E, K70R, M184V, T215Y/F/C/S, K219Q/E; NNRTI DRM included K103N, Y181C, G190A/S/R, L100I, K101E, V106I/M, Y188H/C/L, M230I/L. 2019 Open forum infectious diseases Method HIV D67E;D67N;G190A;G190R;G190S;K101E;K103N;K219E;K219Q;K70R;L100I;M184V;M230I;M230L;M41I;M41L;T215C;T215F;T215S;T215Y;V106I;V106M;Y181C;Y188C;Y188H;Y188L 65;65;141;141;141;159;127;99;99;73;152;79;186;186;57;57;86;86;86;86;166;166;134;175;175;175 71;71;150;150;150;164;132;106;106;77;157;84;193;193;63;63;97;97;97;97;173;173;139;184;184;184 NRTI;NNRTI 0;108 32;113 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Repeated measures logistic regression (generalized estimating equations) was used to identify factors associated with detectable K103N, or other DRMs, in proviral DNA. 2019 Open forum infectious diseases Method HIV K103N 129 134 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Twenty-nine participants were selected on an EFV-based regimen, with a K103N mutation in plasma RNA by population sequencing from ACTG 364 and 5095. 2019 Open forum infectious diseases Method HIV K103N 71 76 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The G112D and M230I mutations were introduced into the p66 coding region using the Multi-Quik change kit (Agilent Technologies) as per the manufacturer's instructions. 2019 Journal of virology Method HIV G112D;M230I 4;14 9;19 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. A twofold molar excess of Alexa Fluor 488-C5-maleimide was then added to the resuspended CA K158C tubes, allowed to react for 1 min and unreacted dye was then quenched by the addition 2-mercaptoethanol to a final concentration of 25 mM. 2019 Retrovirology Method HIV K158C 92 97 Capsid 89 91 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. AF647-CypA A25D binding was imaged by time-lapse total internal reflection fluorescence microscopy (sequential acquisition, 491 nm and 561 nm laser, 20 ms exposure time, one frame per second) after injecting perfringolysin O (200 nM) in VLP imaging buffer (50 mM HEPES pH 7.0, 100 mM NaCl) supplemented with an oxygen quenching system to reduce photobleaching (2 mM trolox, 2.5 mM protocatechuic acid, 0.25 U mL-1 protocatechuate-3,4-dioxygenase). 2019 Retrovirology Method HIV A25D 11 15 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. After induction with 1 mM IPTG and expression at 37 C for 3 h, the cells were harvested by centrifugation, resuspended in cold purification buffer, whereby the buffer composition depended on the mutations because these result in changes of the isoelectric point of the protein: 25 mM HEPES, pH 7.6 [wild type CypA] or pH 7.2 [CypA A25D]; 50 mM MES, pH 6.8 [CypA K27D and CypA K30D]; 50 mM Bicine, pH 8.9 [CypA P29K]; each buffer was supplemented with 1 mM DTT, 0.02% NaN3, 1 mg/mL lysozyme and "Complete" protease inhibitor. 2019 Retrovirology Method HIV A25D;K27D;K30D;P29K 332;363;377;411 336;367;381;415 PR 506 514 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Briefly, biotinylated CA K158C and biotinylated CA hexamer (assembled from CA A14C/E45C/W184A/M185A) were immobilized in separate flow channels of a CM5 sensor chip modified with streptavidin. 2019 Retrovirology Method HIV A14C;E45C;M185A;W184A;K158C 78;83;94;88;25 82;87;99;93;30 Capsid;Capsid;Capsid 22;48;75 24;50;77 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. CA K158C (7.36 mg/ml in 25 mM sodium phosphate buffer, pH 7, 0.02% NaN3, 2 mM DTT) was assembled for 15 min on ice after addition of solid NaCl to a final concentration of 2.5 M. 2019 Retrovirology Method HIV K158C 3 8 Capsid 0 2 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. CA K158C was labeled with Alexa Fluor 488-C5-maleimide at the engineered cysteine residue (Thermo Fisher) after assembly into CA tubes to avoid modification of native cysteine residues. 2019 Retrovirology Method HIV K158C 3 8 Capsid;Capsid 0;126 2;128 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. CypA mutants K27D and K30D were further purified by gel filtration. 2019 Retrovirology Method HIV K27D;K30D 13;22 17;26 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. CypA solutions (0.1-20 mM) were prepared with AF647-CypA (1 muM) and unlabeled CypA (added to make up the desired final concentration) in VLP imaging buffer were assessed, whereby the concentration of the AF647-CypA A25D was used at a maximum concentration of 1 microM. 2019 Retrovirology Method HIV A25D 216 220 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Expression and purification of CA mutants with engineered cysteine residues for cross-linking tubes (CA A14C/E45C) and for site-specific labeling (CA K158C) was carried out using published methods for the purification of CA. 2019 Retrovirology Method HIV A14C;E45C;K158C 104;109;150 108;113;155 Capsid;Capsid;Capsid;Capsid 31;101;147;221 33;103;149;223 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Pooled fractions containing CypA were adjusted in pH (pH 5.8 [wild type CypA]; pH 5.1 [CypA A25D]; pH 6.1 [CypA P29K]) using 1% v/v acetic acid prior to centrifugation at 43,000g, 4 C for 1 h. 2019 Retrovirology Method HIV A25D;P29K 92;112 96;116 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. The coding sequence for human CypA (wild type and mutants A25D, K27D, P29K and K30D) was amplified from the corresponding constructs for mammalian expression (see below) by PCR and cloned into a pET-21 vector using the XhoI and NdeI restriction sites to generate a construct for expression of CypA without purification tags. 2019 Retrovirology Method HIV A25D;K27D;K30D;P29K 58;64;79;70 62;68;83;74 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. The supernatant was injected onto HiTrap SP HP columns (2 x 5 mL connected in series, GE Healthcare) equilibrated with SP buffer, whereby the buffer composition depended on the mutation: 25 mM sodium phosphate, pH 5.8 [wild type CypA]; 50 mM sodium acetate, pH 5.1 [CypA A25D]; 50 mM BIS-TRIS, pH 6.1 [CypA P29K]; each buffer supplemented with 1 mM DTT, 0.02% NaN3. 2019 Retrovirology Method HIV A25D;P29K 271;307 275;311 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Then the flow cell was filled with CA tube assembly mixture (15 muL, delivered at 30 muL/min) containing CA-K158C-AF488 (4 muM), CA A14C/E45C (76 muM) in assembly buffer (50 mM Tris, pH 8, 500 mM NaCl; NaCl was added just before flowing the mixture into the flow channel) and incubated for 25 min to allow the growth of CA tubes on the modified surface. 2019 Retrovirology Method HIV A14C;E45C;K158C 132;137;108 136;141;113 Capsid;Capsid;Capsid;Capsid 35;105;129;320 37;107;131;322 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. TIRF imaging of CypA A25D binding to capsids in permeabilized viral particles. 2019 Retrovirology Method HIV A25D 21 25 Capsid 37 44 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Uniform 15N/13C labeling of wild type CypA and CypA mutants A25K, P29D and P29K was performed by growth in modified minimal medium using 15NH4Cl and 13C6 glucose as the sole nitrogen and carbon sources, respectively. 2019 Retrovirology Method HIV A25K;P29D;P29K 60;66;75 64;70;79 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Wild type CypA and mutants A25D and P29K were further purified by cation exchange chromatography. 2019 Retrovirology Method HIV A25D;P29K 27;36 31;40 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. 2h, bottom), which carry the clickable unnatural amino acid TCO* at position Ser401TAG in V4 and the Q3 tag in V1, were produced by transfecting an engineered amberless full-length HIV-1BG505 Q23 DeltaRT genome, an Env mutant that carries a single amber codon at position Ser401TAG, and a bi-cistronic plasmid that carries the amber suppressor tRNA and PylRSAF (1/3 of the amount of the plasmid that encodes the gene for Env). 2019 Nature Method HIV S401A;S401A;S401G;S401G;S401T;S401T 77;272;77;272;77;272 86;281;86;281;86;281 Env;Env 215;421 218;424 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Clickable HIV-1JR-FL virus (V1-Asn136TAG V4-A1) was produced by transfecting an amberless Q23 backbone DeltaEnv DeltaRT and a JR-FL Env mutant that carries a single amber codon at position Asn136TAG in V1 and the A1 tag in V4 (Extended Data. 2019 Nature Method HIV N136A;N136G;N136T;N136A;N136G;N136T 189;189;189;31;31;31 198;198;198;40;40;40 Env 132 135 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. For example, HIV-1BG505 viruses labelled at Ser401TAG in V4 and V1-Q3 (Extended Data. 2019 Nature Method HIV S401A;S401G;S401T 44;44;44 53;53;53 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Only the V1 and V4 loops, the Q3 and A1 peptides, the linkers, the fluorophores and the solvent were allowed to move; the positions of all core SOS and I559P trimer atoms were fixed. 2019 Nature Method HIV I559P 152 157 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Our system is based on an amber suppressor tRNA and the Y306A Y384F mutant of the Methanosarcina mazei pyrrolysine aminoacyl-tRNA-synthetase (PylRSAF) that accepts the clickable unnatural amino acid transcyclooct-2-ene lysine (TCO*, Sichem). 2019 Nature Method HIV Y306A;Y384F 56;62 61;67 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Tagged HIV-1BG505 Env mutants that contain A501C and T605C (SOS), I559P or SOS and I559P, and HIV-1JR-FL SOS virus were prepared using the same ratio 40:1 of non-tagged Env SOS (or I559P, or SOS and I559P) to Env mutant SOS (or I559P, or SOS and I559P) and double-tagged with V1-Q3 and V4-A1. 2019 Nature Method HIV A501C;I559P;I559P;I559P;I559P;I559P;I559P;T605C 43;66;83;181;199;228;246;53 48;71;88;186;204;233;251;58 Env;Env;Env 18;169;209 21;172;212 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. The infectivity of HIV-1BG505 or HIV-1JR-FL with wild-type or mutant Env that carries SOS, I559P or SOS and I559P mutations:or amber-suppressed Env:was determined using a vector containing an HIV-1 long terminal repeat that expresses a Gaussia luciferase reporter. 2019 Nature Method HIV I559P;I559P 91;108 96;113 LTR;Env;Env 198;69;144 218;72;147 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Consensus IN_CRF and IN_A proteins and those with the mutations Q148K/G140S and G118R/E138K were expressed in Escherichia coli strain Rosetta (DE3) (Novagen) and purified according to . 2019 Acta naturae Method HIV E138K;G118R;G140S;Q148K;E138K;G118R;G140S;Q148K 87;81;71;65;86;80;70;64 92;86;76;70;91;85;75;69 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The vector pET_15b_IN_CRF with the consensus IN_CRF sequence was obtained from the vector pET- 15b_IN_CRF* by sequential site-directed mutagenesis, resulting in the amino acid substitutions I32V and I259V. 2019 Acta naturae Method HIV I259V;I32V;I259V;I32V 200;191;199;190 205;195;204;194 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The vectors encoding IN_CRF with substitutions Q148K/G140S and G118R/E138K were prepared by site-directed mutagenesis of the plasmid pET_15b_ IN_CRF using a QuikChange II Site-Directed mutagenesis kit (Agilent Technologies, USA). 2019 Acta naturae Method HIV E138K;G118R;G140S;Q148K 69;63;53;47 74;68;58;52 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. RT-SHIV contains a T to C substitution at position 8 of the SIV tRNA primer binding site that improves replication. 2019 Nature communications Method HIV T8C 19 52 RT 0 2 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Single E92G/Q, G140R, Q124R, A122T, G118R, I72T, I110V, and I250V or double E92Q + G140R and G118R + A122T mutations were introduced into the SIV IN region using site-directed mutagenesis (SDM). 2019 Nature communications Method HIV A122T;A122T;E92G;E92Q;E92Q;G118R;G118R;G140R;G140R;I110V;I250V;I72T;Q124R 29;101;7;7;76;36;93;15;83;49;60;43;22 34;106;13;13;80;41;98;20;88;54;65;47;27 IN 146 148 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. The clone for triple mutant PRTri (V32I, I47V and V82I) includes optimizing mutations of Q7K, L33I, and L63I to decrease autoproteolysis, and C67A, C95A to eliminate cysteine-thiol oxidation. 2019 Biochemical and biophysical research communications Method HIV C67A;C95A;I47V;L33I;L63I;Q7K;V32I;V82I 142;148;41;94;104;89;35;50 146;152;45;98;108;92;39;54 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Crystals of inhibitor-free PRS17-D25N were obtained from 1.95 M sodium chloride and 0.1 M bis-Tris pH 7.5. 2019 ACS omega Method HIV D25N 33 37 PR 27 29 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Synthetic genes encoding the 99 amino acid protein named PRS17 and its active-site mutant PRS17-D25N (DNA2.0, Menlo Park, CA) were cloned in pJ414 vector flanked by Nde1 and BamHI sites and transformed into Escherichia coli BL-21 (DE3, Stratagene). 2019 ACS omega Method HIV D25N 96 100 Capsid;PR;PR 122;57;90 124;59;92 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The crystal structures of PRS17 active-site mutant PRS17-D25N and the substrate analogue complexes PR/CA-p2, PRS17/CA-p2, PRS17-P41/p2-NC, and PRS17-P61/p2-NC were solved by molecular replacement using PHASER. 2019 ACS omega Method HIV D25N 57 61 NC;NC;Capsid;Capsid;PR;PR;PR;PR;PR;PR 135;156;102;115;26;51;99;109;122;143 137;158;104;117;28;53;101;111;124;145 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The previously solved crystal structure of active PRS17 (5T2E) was used as the starting model for PRS17 active-site mutant PRS17-D25N. 2019 ACS omega Method HIV D25N 129 133 PR;PR;PR 50;98;123 52;100;125 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The PRS17/CA-p2 complex was refined using REFMAC, while the PRS17-D25N and PRS17/p2-NC complexes were initially refined by SHELX-2014 and switched to REFMAC during later cycles of refinement. 2019 ACS omega Method HIV D25N 66 70 NC;Capsid;PR;PR;PR 84;10;4;60;75 86;12;6;62;77 31269034 Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study. Prevalence of acquired drug resistance mutations represents the number of HIV-positive individuals with virological non-suppression and majority virus harboring acquired NNRT-class, K65R and/or M184V mutations (occurring as single or multiple drug-resistant viral variants/mutants), divided by the number of HIV-positive individuals with virological non-suppression and acquired drug-resistant majority virus, at a given time. 2019 PloS one Method HIV K65R;M184V 182;194 186;199 31269034 Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study. The following drug resistance mutations (associated with antiretrovirals) are modeled: i) Nucleoside reverse transcriptase (NRTI)-associated signature mutations :M184V (XTC), K65R (TDF) and the thymidine analogue mutations / TAMs (AZT); ii) Non-nucleoside reverse transcriptase (NNRTI)-associated class mutations (EFV/NVP); and iii) Protease inhibitor (PI)-associated class mutations (LPV). 2019 PloS one Method HIV K65R;M184V 175;162 179;167 NNRTI;NRTI;PR;NNRTI;NRTI;PI 241;90;333;279;124;353 277;122;341;284;128;355 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. A homology model of KY that has previously been reported was used to construct models for KY(V89L), KY(M90L), and KY(DM). 2019 Biochemistry Method HIV M90L;V89L 103;93 107;97 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. A Q7K mutation was included to prevent autoproteolysis. 2019 Biochemistry Method HIV Q7K 2 5 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Cleavage of p55 polyprotein by the HIV-1 protease of interest (NL4-3, KY, or KY(V89L)) was monitored by SDS-PAGE of cleavage products. 2019 Biochemistry Method HIV V89L 80 84 PR 41 49 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Darunavir was used as a negative control for the KY and KY(V89L) experiments. 2019 Biochemistry Method HIV V89L 59 63 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Diffraction quality crystals of NL4-3, NL4-3(L89V), and NL4-3(L90M) were flash frozen under a cryostream when mounting the crystal to a Saturn 944 x-ray detector (Rigaku, USA). 2019 Biochemistry Method HIV L89V;L90M 45;62 49;66 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. DRV was incubated for 1 hour with 0.35 nM HIV-1 protease for NL4-3 WT and NL4-3(L89V), 1 nM for NL4-3(L90M) and NL4-3(DM), and 5 nM for the KY variants prepared in 2X assay buffer [100 mM sodium acetate at pH 5.5 and 200 mM sodium chloride]. 2019 Biochemistry Method HIV L89V;L90M 80;102 84;106 PR 48 56 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. For the simulations of the wild-type protease and its close relatives, high resolution crystal structures of NL4-3, NL4-3(L89V), NL4-3(L90M) and NL4-3(DM) co-crystallized with DRV were used (PDB: 6DGX, 6OOU, 6OOS, 6OOT) with crystallographic water molecules included. 2019 Biochemistry Method HIV L89V;L90M 122;135 126;139 PR 37 45 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Gag cleavage by the protease of interest was monitored at 2, 5, 10, 15, 20, 30, 45, and 60 minutes for NL4-3 and 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, and 180 minutes for KY and KY(V89L). 2019 Biochemistry Method HIV V89L 182 186 PR;Gag 20;0 28;3 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The expression, isolation, and purification of NL4-3, NL43(L89V), NL4-3(L90M), NL4-3(DM), and KY variants used for all assays were carried out as previously described. 2019 Biochemistry Method HIV L89V;L90M 59;72 63;76 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The reaction was immediately initiated by the addition of 5 muL of 120 nM of HIV-1 protease (NL4-3, NL4-3(L89V), NL43(L90M), NL4-3(DM), and the KY variants) using a PerkinElmer EnVision plate reader. 2019 Biochemistry Method HIV L89V;L90M 106;118 110;122 PR 83 91 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. WT, KY or KY V89L), 2 muM of protease were added to 48.2 muM of p55 Gag polyprotein. 2019 Biochemistry Method HIV V89L 13 17 PR;Gag 29;68 37;71 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Briefly, C-SA HIV protease and mutant E35D G S were cloned in pGEX-6P-1 and expressed in Escherichia coli BL21 (DE3) pLysS. 2019 Journal of enzyme inhibition and medicinal chemistry Method HIV E35D 38 42 PR 18 26 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Enzymatic activity of the HIV-1 C-SA and mutant (E35D G S) protease was measured by following the hydrolysis of the HIV-PR chromogenic substrate, Lys-Ala-Arg-Val-Nle-nPhe-Glu-Ala-Nle-NH2 as reported before. 2019 Journal of enzyme inhibition and medicinal chemistry Method HIV E35D 49 54 PR;PR 59;120 67;122 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Inhibition constants, Ki, for the inhibitors (Amprenavir, APV; Atazanavir, ATV; Darunavir, DRV, Indinavir, IDV; Nelfinavir, NFV; Lopinavir, LPV; Ritonavir, RTV; Saquinavir, SQV; Tipranavir, TPV) against E35D G S were obtained at 37 C. 2019 Journal of enzyme inhibition and medicinal chemistry Method HIV E35D 203 207 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Molecular docking was performed using the AutoDock software in order to ensure that the inhibitors are in an accurate orientation in the active site of E35D G S mutant relative to the wild-type. 2019 Journal of enzyme inhibition and medicinal chemistry Method HIV E35D 152 156 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The homology structure prediction of E35D G S variant was generated using SWISS-MODEL. 2019 Journal of enzyme inhibition and medicinal chemistry Method HIV E35D 37 41 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The model prediction of the E35D G S variant was made using the PDB ID 3U71 structure of the South African wild-type HIV-1 subtype-C as a template and this was based on the highest sequence identity of 95.96%. 2019 Journal of enzyme inhibition and medicinal chemistry Method HIV E35D 28 32 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Primary INSTI resistance (-R) substitutions were T66I/A/K, E92Q/G, T97A, F121Y, Y143R/H/C, S147G, Q148H/K/R, N155H/S and R263K in IN. 2019 The Journal of antimicrobial chemotherapy Method HIV E92G;E92Q;F121Y;N155H;N155S;Q148H;Q148K;Q148R;R263K;S147G;T66A;T66I;T66K;T97A;Y143C;Y143H;Y143R 59;59;73;109;109;98;98;98;121;91;49;49;49;67;80;80;80 65;65;78;116;116;107;107;107;126;96;57;57;57;71;89;89;89 INSTI;IN 8;130 13;132 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Primary NNRTI-R substitutions were L100I, K101E/P, K103N/S, V106M/A, V108I, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188C/H/L, G190A/E/Q/S, H221Y, P225H, F227C and M230L/I in RT. 2019 The Journal of antimicrobial chemotherapy Method HIV E138A;E138G;E138K;E138Q;E138R;F227C;G190A;G190E;G190Q;G190S;H221Y;K101E;K101P;K103N;K103S;L100I;M230I;M230L;P225H;V106A;V106M;V108I;V179L;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 76;76;76;76;76;147;120;120;120;120;133;42;42;51;51;35;157;157;140;60;60;69;91;98;98;98;109;109;109 89;89;89;89;89;152;131;131;131;131;138;49;49;58;58;40;164;164;145;67;67;74;96;107;107;107;118;118;118 NNRTI;RT 8;168 13;170 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Primary NRTI-R substitutions were M41L, K65R/E/N, D67N, T69 insertions, K70E/R, L74V/I, Y115F, Q151M, M184V/I, L210W, T215Y/F and K219E/Q/N/R in RT. 2019 The Journal of antimicrobial chemotherapy Method HIV D67N;K219E;K219N;K219Q;K219R;K65E;K65N;K65R;K70E;K70R;L210W;L74I;L74V;M184I;M184V;M41L;Q151M;T215F;T215Y;Y115F 50;130;130;130;130;40;40;40;72;72;111;80;80;102;102;34;95;118;118;88 54;141;141;141;141;48;48;48;78;78;116;86;86;109;109;38;100;125;125;93 NRTI;RT 8;145 12;147 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Primary PI-R substitutions were D30N, V32I, M46I/L, I47V/A, G48V, I50V/L, I54M/L, Q58E, T74P, L76V, V82A/F/L/S/T, N83D, I84V, N88S and L90M in PR. 2019 The Journal of antimicrobial chemotherapy Method HIV D30N;G48V;I47A;I47V;I50L;I50V;I54L;I54M;I84V;L76V;L90M;M46I;M46L;N83D;N88S;Q58E;T74P;V32I;V82A;V82F;V82L;V82S;V82T 32;60;52;52;66;66;74;74;120;94;135;44;44;114;126;82;88;38;100;100;100;100;100 36;64;58;58;72;72;80;80;124;98;139;50;50;118;130;86;92;42;112;112;112;112;112 PI;PR 8;143 10;145 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Secondary INSTI-R substitutions were M50I, H51Y, L68V/I, V72A/N/T, L74M, Q95K/R, G118R, S119P/R/T, F121C, A128T, E138K/A, G140A/C/S, P145S, Q146R/I/K/L/P, V151L/A, S153A/F/Y, E157K/Q, G163K/R and E170A in IN. 2019 The Journal of antimicrobial chemotherapy Method HIV A128T;E138A;E138K;E157K;E157Q;E170A;F121C;G118R;G140A;G140C;G140S;G163K;G163R;H51Y;L68I;L68V;L74M;M50I;P145S;Q146I;Q146K;Q146L;Q146P;Q146R;Q95K;Q95R;S119P;S119R;S119T;S153A;S153F;S153Y;V151A;V151L;V72A;V72N;V72T 106;113;113;175;175;196;99;81;122;122;122;184;184;43;49;49;67;37;133;140;140;140;140;140;73;73;88;88;88;164;164;164;155;155;57;57;57 111;120;120;182;182;201;104;86;131;131;131;191;191;47;55;55;71;41;138;153;153;153;153;153;79;79;97;97;97;173;173;173;162;162;65;65;65 INSTI;IN 10;205 15;207 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. HIV-Gag-iGFPDeltaEnv and psPAX2 were used as described by Mamede et al., and the CA sequences of both plasmids were mutated: RGDA/Q112D, RGDA/Q112D+Q4R, and RGDA/Q112D+G94D/G116R. 2019 Journal of virology Method HIV G116R;G94D;Q112D;Q112D;Q112D;Q4R 173;168;162;130;142;148 178;172;167;135;147;151 Gag;Capsid 4;81 7;83 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Jurkat cells infected with the RGDA/Q112D virus were harvested for DNA extraction at 92 days after infection. 2019 Journal of virology Method HIV Q112D 36 41 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The cells were then infected with 100 ng (p24) of the NL-VifS virus encoding the RGDA/Q112D mutation. 2019 Journal of virology Method HIV Q112D 86 91 p24;Vif 42;57 45;60 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Additionally, E64K and A316W mutations were introduced into the gp120 to stabilize the pre-CD4 bound conformation and prevent V3 loop exposure. 2019 PLoS pathogens Method HIV A316W;E64K 23;14 28;18 gp120 64 69 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. CH505TF.N279K.G458Y.SOSIP.664 was stabilized using a BG505 chimeric design where the CH505TF gp120 was grafted into the BG505 SOSIP gp140 sequence resulting in 29 amino acid changes from the parental CH505TF sequence. 2019 PLoS pathogens Method HIV G458Y;N279K 14;8 19;13 gp120;gp140 93;132 98;137 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. N279K and G458Y mutations were added to this SOSIP design in various combinations. 2019 PLoS pathogens Method HIV G458Y;N279K 10;0 15;5 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The sequences were replaced with those of the CH505TF.N279K.G458Y.SOSIP.664 trimer and CH235 UCA2, respectively using Coot. 2019 PLoS pathogens Method HIV G458Y;N279K 60;54 65;59 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. To prepare Env complexes, CH505TF.N279K.G458Y.SOSIP.664 at a final concentration of 1 mg/ml was incubated with 4-5-fold molar excess of the CH235 UCA2 Fab fragments for 30-60 minutes. 2019 PLoS pathogens Method HIV G458Y;N279K 40;34 45;39 Env 11 14 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Luciferase reporter variants of NL4-3 (RepRluc Gag P373S) contained the Renilla luciferase (Rluc) gene in the nef locus as previously described. 2019 PloS one Method HIV P373S 51 56 Nef;Gag 110;47 113;50 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. MT-2 cells (0.1 x 106 cells/mL) were infected with RepRluc Gag P373S or reporter-free Gag variants at a MOI of 0.01. 2019 PloS one Method HIV P373S 63 68 Gag;Gag 59;86 62;89 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Participants with a history of genotypic/phenotypic drug resistance to protease inhibitors (PIs) or with HIV-1 genotypic drug resistance to PIs at baseline (including D30N, M46I/L, I47V/A, G48V, I50L, I54M/L, Q58E, T74P, L76V, V82A/F/L/T/S, N83D, I84V, N88S, or L90M) were excluded, despite any reported effects of PI resistance or resistance markers on GSK3532795 susceptibility (15). 2019 PloS one Method HIV D30N;G48V;I47A;I47V;I50L;I54L;I54M;I84V;L76V;L90M;M46I;M46L;N83D;N88S;Q58E;T74P;V82A;V82F;V82L;V82S;V82T 167;189;181;181;195;201;201;247;221;262;173;173;241;253;209;215;227;227;227;227;227 171;193;187;187;199;207;207;251;225;266;179;179;245;257;213;219;239;239;239;239;239 PR;PI;PI;PI 71;92;140;315 79;95;143;317 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The Gag P373S substitution was included to better represent the subtype B clinical population: S373 is near the SP1 cleavage site and is present in 60% of subtype B isolates. 2019 PloS one Method HIV P373S 8 13 SP1;Gag 112;4 115;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Virus stocks used to initiate selection were generated by transfecting 293T cells (Lipofectamine PLUS kit, Invitrogen) with proviral DNA clones of NL4-3 Gag P373S (hereafter referred to as wild-type) and NL4-3 Gag P373S with additional defined Gag amino acid substitutions introduced by site-directed mutagenesis. 2019 PloS one Method HIV P373S;P373S 157;214 162;219 Gag;Gag;Gag 153;210;244 156;213;247 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. The protein, originally in an inactive form through a D25N mutation, was un-mutated to the wild-type using the VMD Mutator plugin. 2019 The journal of physical chemistry. B Method HIV D25N 54 58 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. A Q577R mutant version was generated via site-directed mutagenesis using the QuikChange protocol (Stratagene). 2019 Retrovirology Method HIV Q577R 2 7 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Coordinates for the PIE12/IQN17-Q577R complex structure are available at the protein data bank (PDB code: 6PSA). 2019 Retrovirology Method HIV Q577R 32 37 PI 20 22 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. KG-PIE12 was crystallized in complex with Se-Met-IQN17-Q577R (1:1.1 IQN17:KG-PIE12, 10 mg/mL total in water) at 21 C in Hampton Research condition SaltRx HT B4 (1.8 M ammonium citrate dibasic, 0.1 M sodium acetate trihydrate, pH 4.6) by sitting-drop vapor diffusion. 2019 Retrovirology Method HIV Q577R 55 60 PI;PI 3;77 5;79 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. SelMet-IQN17-Q577R and HIV C34 were synthesized on a PS3 peptide synthesizer (Protein Technologies, Inc.) at 80 micromol scale on NovaPEG Rink Amide LL resin (Novabiochem) and Rink Amide AM resin LL (Novabiochem), respectively, via Fmoc-SPPS and were purified by RP-HPLC. 2019 Retrovirology Method HIV Q577R 13 18 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Stocks (~ 50 nM) of biotinylated IZN36 (WT and Q577R mutant) were prepared in running buffer in the presence of 1.2x molar excess of HIV C34 and captured on the surface to a density of 100-200 RUs. 2019 Retrovirology Method HIV Q577R 47 52 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The IQN17-Q577R/PIE12 structure was determined by molecular replacement using PHASER with PIE12-IQN17 (PDB structure 3L37) as the search model. 2019 Retrovirology Method HIV Q577R 10 15 PI;PI 16;90 18;92 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The point mutants (CGG for Q577R, AAG for Q577K and AAC for Q577N) were introduced using the Q5 site-directed mutagenesis kit with primers designed using NEBuilder software (NEB). 2019 Retrovirology Method HIV Q577K;Q577N;Q577R 42;60;27 47;65;32 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The Q577K forward primer was CAAACAGCTCAAGGCAAGAATCC, and the reverse primer was the same as that for Q577N. 2019 Retrovirology Method HIV Q577K;Q577N 4;102 9;107 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The Q577N forward and reverse primers were CAAACAGCTCAACGCAAGAATCCTGG and ATGCCCCAGACTGTGAGT. 2019 Retrovirology Method HIV Q577N 4 9 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The Q577R forward and reverse primers were CAAACAGCTCCGGGCAAGAATCC and ATGCCCCAGACTGTGAGTT. 2019 Retrovirology Method HIV Q577R 4 9 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The Q577R, Q577N and Q577K point mutant viral vectors were generated by excising the env region of the WT pNL4-3 genome using XhoI and EcoRI (NEB) and ligating into pET20b (Novagen), a shuttle vector we used for mutagenesis. 2019 Retrovirology Method HIV Q577K;Q577N;Q577R 21;11;4 26;16;9 Env 85 88 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. As initial attempts at the weighting procedure yielded 2 groups that were exceedingly heterogenous (Supplementary Figure 1S), we performed the final weighted analysis only on the subpopulation of the 580 patients who had failed on an ART regimen prior to ABC/3TC/DTG initiation, with and without a documented M184V/I mutation. 2019 Open forum infectious diseases Method HIV M184I;M184V 309;309 316;316 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Information on thymidine analogue mutations (TAMs; M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E) before the switch to ABC/3TC/DTG also was obtained. 2019 Open forum infectious diseases Method HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 57;89;89;63;69;51;76;76 61;96;96;67;74;55;83;83 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. The presence of M184V/I mutations was established by the cumulative resistance profile available before the switch to ABC/3TC/DTG, including resistance tests performed before any treatment was started for a fraction of patients. 2019 Open forum infectious diseases Method HIV M184I;M184V 16;16 23;23 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. The primary objective was to explore the effectiveness of ABC/3TC/DTG among treatment-experienced patients with or without a documented M184V/I mutation. 2019 Open forum infectious diseases Method HIV M184I;M184V 136;136 143;143 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. The propensity scores were then converted to the inverse proportional weights where the weight was set as equal to 1/e(x) for individuals with M184V/I and 1/[1- e(x)] for individuals without the mutation. 2019 Open forum infectious diseases Method HIV M184I;M184V 143;143 150;150 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. To calculate the weights, we used multivariate logistic regression modeling of the likelihood of a patient having the M184V/I mutation to calculate the propensity score (e(x)), which indicates the calculated probability of each patient having the M184V/I mutation based on the following confounders: age; sex; body mass index; race; VL before the first antiretroviral regimen above or below 100 000 copies/mL; CD4 nadir; number of TAMs from pre-ABC/3TC/DTG genotypes; transmission route; years of HIV infection; months of viral suppression before the switch to ABC/3TC/DTG; and previous protease or integrase inhibitor exposure. 2019 Open forum infectious diseases Method HIV M184I;M184I;M184V;M184V 118;247;118;247 125;254;125;254 IN;PR 599;587 608;595 HIV infections 497 510 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. With regards to the propensity score distributions, we observed an improved overlap between the M184V/I and non-M184V/I population when restricted to those with previous VF, which led to a convergence in their characteristics (Supplementary Figure 1S, Supplementary Table S1). 2019 Open forum infectious diseases Method HIV M184I;M184I;M184V;M184V;M184I;M184I;M184V;M184V 97;113;97;113;96;112;96;112 104;120;104;120;103;119;103;119 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Point mutations were introduced into nef sequences using overlap extension PCR, including G2A substitutions in both reference clones that served as negative controls. 2019 Cell reports Method HIV G2A 90 93 Nef 37 40 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Wild-type NL4.3 served as a positive control, while strains encoding G2A or premature stop codons at positions 31 and 33 (referred to as DeltaNef) were used as negative controls for infectivity and replication assays. 2019 Cell reports Method HIV G2A 69 72 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. HEK-293T cells (3 x 105 in a 6-well plates) were co-transfected with different plasmids using PEI25k to express the tagged proteins: HA-wt-HDAC6 (1 mug), wt-Nef-EGFP (0.5 mug), Nef-G2A-EGFP (0.5 mug), and Nef-PPAA-EGFP (0.5 mug). 2019 Frontiers in microbiology Method HIV G2A 181 184 Nef;Nef;Nef 157;177;205 160;180;208 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Vectors for expression of full-length wild-type (wt) or mutated HIV-1Lai-Nef were constructed in the pRcCMV plasmid, and Nef mutants (Nef-G2A; Nef-E160A, Nef-EA; Nef-LL164-5/AA, Nef-LLAA; and Nef-P72xxP75/A, Nef-PPAA) were generated by PCR-directed mutagenesis using appropriate primers as described. 2019 Frontiers in microbiology Method HIV E160A;G2A 147;138 152;141 Nef;Nef;Nef;Nef;Nef;Nef;Nef;Nef;Nef 73;121;134;143;154;162;178;192;208 76;124;137;146;157;165;181;195;211 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Bluescript KS-JCV Mad-1 Agno L33D + E34L mutant was generated with Ouik Change mutagenesis kit using a Bluescript KS-JCV Mad-1 WT plasmid as template and specific oligonucleotides. 2020 Virology Method HIV E34L;L33D 36;29 40;33 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Briefly, the plasmid constructs (Bluescript KS-JCV Mad-1 WT, Bluescript KS-JCV Mad-1 Agno mutant (L33D + E34L) were digested with BamHI to liberate the inserts from the vector (Bluescript KS+). 2020 Virology Method HIV E34L;L33D 105;98 109;103 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. GST-Agno L33D + E34L mutant was generated with Quik Change mutagenesis kit using pGEX-1lambdat-JCVAgno as a template and specific mutagenic oligos. 2020 Virology Method HIV E34L;L33D 16;9 20;13 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Transfection/infection of SVG-A cells were carried out in SVG-A cells by using Bluescript KS-JCV Mad-1 WT and Bluescript KS-JCV Mad-1 Agno mutant (L33D + E34L) as described under replication assays above. 2020 Virology Method HIV E34L;L33D 154;147 158;152 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Two micrograms of either GST alone or GST-Agno or GST-Agno mutant (L33D + E34L immobilized on glutathione-4B Sepharose beads (Glutathione Sepharose 4B, GE healthcare, catalog no. 2020 Virology Method HIV E34L;L33D 74;67 78;72 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Because some individuals may have been exposed to thymidine analogs before TDF-containing regimens, we excluded individuals with sequences containing TAMs:M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E. 2020 The Journal of infectious diseases Method HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 161;193;193;167;173;155;180;180 165;200;200;171;178;159;187;187 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Estimates of the standard error in each study were calculated by dividing the pooled estimate of the standard deviation by the square root of the number of patients with/without M184I/V in any given study. 2020 The Journal of infectious diseases Method HIV M184I;M184V 178;178 185;185 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Next, we used Fisher's exact test to identify mutations associated with M184I/V. 2020 The Journal of infectious diseases Method HIV M184I;M184V 72;72 79;79 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. To assess whether M184I/V was associated with VL failure independently of other mutations, we performed a separate analysis in which we used a mixed linear regression model adjusting for study as a random effect and other mutations associated with increased VL (which were identified by forward stepwise variable selection). 2020 The Journal of infectious diseases Method HIV M184I;M184V 18;18 25;25 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. To quantify the impact of M184I/V on VL, we calculated mean log10 VL in each study according to M184I/V. 2020 The Journal of infectious diseases Method HIV M184I;M184I;M184V;M184V 26;96;26;96 33;103;33;103 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We graphically compared the distribution of log10 VLs according to presence of M184I/V mutation both within and across studies. 2020 The Journal of infectious diseases Method HIV M184I;M184V 79;79 86;86 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We repeated this process in subgroups of patients defined by several baseline characteristics: presence of K65R mutation, presence of major NNRTI mutations, choice of NRTI, choice of NNRTI, categories of baseline CD4 count (< and >200 cells/mm3), and categories of baseline VL (< and >100 000 copies per mL). 2020 The Journal of infectious diseases Method HIV K65R 107 111 NNRTI;NNRTI;NRTI 140;183;167 145;188;171 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Env-expressing plasmids pCMV/R-Env with E560K, E560D or E560G were created by overlapped PCR using pCMV/R-Env(LAI) wild type (Genebank No. 2019 Retrovirology Method HIV E560D;E560G;E560K 47;56;40 52;61;45 Env;Env;Env 0;31;106 3;34;109 31818716 Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial. Peripheral blood mononuclear cells were evaluated for NNRTI and NRTI drug resistance mutations, K103N, Y181C, G190A, and K65R, and M184V, using a quantitative OLA. 2020 The lancet. HIV Method HIV G190A;K103N;K65R;M184V;Y181C 110;96;121;131;103 115;101;125;136;108 NNRTI;NRTI 54;64 59;68 31818716 Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial. We classified participants prospectively as positive for ART resistance if any one of the HIV pol codons K103N, Y181C, G190A, or M184V had the drug-resistant genotype detected by OLA at >=10% frequency within the individual's viral quasispecies. 2020 The lancet. HIV Method HIV G190A;K103N;M184V;Y181C 119;105;129;112 124;110;134;117 Pol 94 97 31818716 Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial. We evaluated K65R in all pre-ART specimens retrospectively as tenofovir became more available concomitantly with efavirenz. 2020 The lancet. HIV Method HIV K65R 13 17 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. The proportion of patients with M184 V/I, K103 N/S, and K65R mutations, as well as the presence of thymidine analogue mutations (TAMs) were also reported. 2019 BMC public health Method HIV K103N;K103S;K65R;M184I;M184V 42;42;56;32;32 50;50;60;40;40 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Crystals of the binary WT and M184V RT-DNA complex were grown by hanging drop vapor diffusion over a mother liquor containing 2-4% PEG 4000, 100 mM MES (pH = 6.0), and 10 mM MgSO4 at either 4 or 20 C. 2019 Communications biology Method HIV M184V 30 35 RT 36 38 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Molecular replacement was performed by the refinement package Phenix using the starting model PDB code 3KK1 (ternary complex) for WT and M184V structures. 2019 Communications biology Method HIV M184V 137 142 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Site-directed mutagenesis to generate the M184V the mutation in both p66 and p51 subunits was performed using the QuickChange II kit (Stratagene, La Jolla, CA) according to manufacturer's protocol. 2019 Communications biology Method HIV M184V 42 47 Capsid 156 158 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The molecular replacement for the structure of binary M184V RT-DNA was determined using PDB code 3KJV (binary complex) as the starting model. 2019 Communications biology Method HIV M184V 54 59 RT 60 62 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The X in the primer sequence represents N2-cystamine-deoxyguanosine which covalently cross-links to Q258C in the p66 subunit. 2019 Communications biology Method HIV Q258C 100 105 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. Mutations M184V and K65R conferring resistance to nucleoside RT inhibitors (NRTI) and K103N and G190S conferring resistance to nonnucleoside RT inhibitors (NNRTI) were introduced into p6HRT_A by site-directed mutagenesis (Evrogen) generating plasmids p6HRT_An (65/184) and p6HRT_Ann (103/190), respectively. 2019 Oxidative medicine and cellular longevity Method HIV G190S;K103N;K65R;M184V 96;86;20;10 101;91;24;15 NNRTI;NRTI;RT;RT 156;76;61;141 161;80;63;143 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Mutation Q7K was introduced to reduce autoproteolysis and C67A and C95A to eliminate cysteine thiol crosslinking. 2020 The FEBS journal Method HIV C67A;C95A;Q7K 58;67;9 62;71;12 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. For cases of M184V/I with clinical data available, we conducted time-to-event analyses for the outcomes of subsequent viral suppression and appearance of first new major DRM. 2020 HIV medicine Method HIV M184I;M184V 13;13 20;20 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. People with viral suppression prior to ART regimen change after detection of the M184V/I mutation or in whom there were no VL measurements after ART change were not included. 2020 HIV medicine Method HIV M184I;M184V 81;81 88;88 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. PLHIV were included in whom a change in ART regimen (or first-line initiation) was recorded within 1 year of detection of M184V/I, with 3TC/FTC in the new regimen being the primary predictor of interest. 2020 HIV medicine Method HIV M184I;M184V 122;122 129;129 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The prevalence of the M184V/I DRM was assessed in relation to calendar time stratified by whether PLHIV were recorded as ART-naive or ART-experienced. 2020 HIV medicine Method HIV M184I;M184V 22;22 29;29 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The rationale for the latter subgroup division is the reported link between M184V/I and TFV sensitivity, and the fact that tenofovir disoproxil fumarate (TDF) became the most common choice of NRTI towards the end of the timeframe considered. 2020 HIV medicine Method HIV M184I;M184V 76;76 83;83 NRTI 192 196 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. The OLA detected mutations conferring high-level resistance to NVP/EFV (K103N, Y181C, G190A), 3TC (M184V) and beginning in 2010 to TDF (K65R) using probes optimized for HIV type-1 subtypes A, D and C. 2020 EClinicalMedicine Method HIV G190A;K103N;K65R;M184V;Y181C 86;72;136;99;79 91;77;140;104;84 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. The complex structure was obtained from the Protein Data Bank (WT RT: 1TL1, Y181C RT: 1JLB, K103N-Y181C double-mutated RT: 5VQY, L100I-K103N double-mutated RT: 2ZE2). 2020 European journal of medicinal chemistry Method HIV K103N;K103N;L100I;Y181C;Y181C 92;135;129;76;98 97;140;134;81;103 RT;RT;RT;RT 66;82;119;156 68;84;121;158 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Macaques G1015R and G1020R were intrarectally infected with SHIV1157ipd3N4 and followed up for over seven years, with detectable viral loads throughout the infection. 2020 Viruses Method HIV G1015R;G1020R 9;20 15;26 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Viral RNA was extracted from the plasma samples from G1015R using QiaAmp Viral RNA Mini kit (Qiagen; Valencia, CA, USA), followed by reverse transcription with superscript III reverse transcriptase (Invitrogen, Grand Island, NY, USA). 2020 Viruses Method HIV G1015R 53 59 RT;RT;Capsid 133;176;111 154;197;113 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Four patients infected with CRF01_AE who failed treatment and carried the K65R and S68G double mutations were selected from a large-scale long-term ART cohort at the First Affiliated Hospital, China Medical University (Shenyang, China) (Additional file 1: Figure S1). 2020 BMC infectious diseases Method HIV K65R;S68G 74;83 78;87 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Occurrence of S68G and K65R/S68G mutations among various subtypes of HIV-1. 2020 BMC infectious diseases Method HIV K65R;S68G;S68G 23;14;28 27;18;32 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Patient-derived PCR products containing the K65R/S68G double mutations were cloned into a pNL4-3-DeltaE-Luc plasmid through a ApaI/AgeI double-enzyme digestion and T4 ligation strategy to produce the pNL4-3-DeltaE-Luc K65R/S68G clone. 2020 BMC infectious diseases Method HIV K65R;K65R;S68G;S68G 44;218;49;223 48;222;53;227 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. PR genes and RT genes of the pNL4-3-wildtype plasmid were replaced by patient-derived genes containing K65R/S68G double mutations through an ApaI/AgeI double-enzyme digestion and T4 ligation strategy to produce the pNL4-3-wildtype K65R/S68G mutant infectious clone. 2020 BMC infectious diseases Method HIV K65R;K65R;S68G;S68G 103;231;108;236 107;235;112;240 PR;RT 0;13 2;15 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Pseudoviruses were packaged in 293 T cells with plasmid VSVG and co-transfection of the K65R/S68G clone or K65R/S68G clone. 2020 BMC infectious diseases Method HIV K65R;K65R;S68G;S68G 88;107;93;112 92;111;97;116 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Subsequently, the S68G mutation was reversed to wild-type through in vitro site-directed mutagenesis using primers G68S-F (5'-AAGAGAAAGGACAGTACCAAATGGAGAAAG-3') and G68S-R(5'-TCTCCATTTGGTACTGTCCTTTCTCTTTAT-3') to produce the pNL4-3-DeltaE-Luc K65R clone. 2020 BMC infectious diseases Method HIV G68S;G68S;K65R;S68G 115;165;243;18 119;169;247;22 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Subsequently, the S68G mutation was reverted to wild type through in vitro site-directed mutagenesis to produce the pNL4-3-wildtype K65R mutant infectious clone. 2020 BMC infectious diseases Method HIV K65R;S68G 132;18 136;22 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The chi-squared test was used to evaluate the frequency of S68G mutation between RTI-naive and -treated individuals, and the K65R/S68G double mutation among HIV-1 subtypes. 2020 BMC infectious diseases Method HIV K65R;S68G;S68G 125;59;130 129;63;134 RT 81 84 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The K65R mutant and K65R/S68G mutant viral stocks were produced via transfection of 293 T cells, and cultured at 37 C in an atmosphere of 5% CO2 for 48 h. 2020 BMC infectious diseases Method HIV K65R;K65R;S68G 4;20;25 8;24;29 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The K65R/S68G mutants and K65R mutants viral stocks were diluted and mixed at a 4:6, 1:1, and 9:1 ratio, respectively. 2020 BMC infectious diseases Method HIV K65R;K65R;S68G 4;26;9 8;30;13 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The nonparametric t-test was used to analyze differences in FC between K65R alone and K65R/S68G double mutants. 2020 BMC infectious diseases Method HIV K65R;K65R;S68G 71;86;91 75;90;95 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The prevalence of S68G mutation and K65R/S68G double mutation among various subtypes of HIV-1 was analyzed in reverse transcriptase inhibitor (RTI)-naive and RTI-treated individuals from the HIV Drug Resistance Database of Stanford University (https://hivdb.stanford.edu/cgi-bin/MutPrevBySubtypeRx.cgi; version of 19 April 2019). 2020 BMC infectious diseases Method HIV K65R;S68G;S68G 36;18;41 40;22;45 RT;RT;RT 110;143;158 131;146;161 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Antiviral assays using HIV-1WT and replication-competent HIV-1 variants (HIVQ151M, HIV3MB, HIV3MB/M184V, and HIV3MB/F160M/M184V) were also conducted, as previously described. 2020 Scientific reports Method HIV F160M;M184V;M184V 116;122;98 121;127;103 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Crystals of HIV-1 RT3MB:DNA and RT3MB/F160M/M184V:DNA binary complexes were obtained by the hanging-drop vapor diffusion method at 20 C with 24-well crystallization plates. 2020 Scientific reports Method HIV F160M;M184V 38;44 43;49 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. The mature p66-p51 heterodimeric HIV-1 RTs (HIV-1 RTWT, RTQ151M, RT3MB, RT3MB/M184V, and RT3MB/F160M/M184V) were produced using E. 2020 Scientific reports Method HIV F160M;M184V;Q151M;M184V 95;101;58;78 100;106;63;83 RT;RT 39;56 42;58 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. The model refinement was performed with the program REFMAC5 in the CCP4 program package, using the atomic model of RTQ151M:DNA:ETV-TP ternary complex (PDB code, 5XNL), excluding solvents and ligands as a starting model. 2020 Scientific reports Method HIV Q151M 117 122 RT 115 117 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. The resultant RT3MB:DNA and RT3MB/F160M/M184V:DNA binary complexes were loaded on HiLoad 16/600 Superdex 200 pg gel-filtration column (GE Healthcare) with buffer containing 10 mM Tris-HCl pH 8.0 and 50 mM NaCl. 2020 Scientific reports Method HIV F160M;M184V 34;40 39;45 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Longitudinal plasma samples between baseline and TF from four cases with Y181C and L228R mutations were selected. 2020 BMC infectious diseases Method HIV L228R;Y181C 83;73 88;78 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Temporal analysis of Y181C/ L228R mutations by deep sequencing. 2020 BMC infectious diseases Method HIV L228R;Y181C 28;21 33;26 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The presence and frequency of IAS-USA resistance-associated mutations in integrase, in addition to L74I, was assessed. 2020 The Journal of antimicrobial chemotherapy Method HIV L74I 99 103 IN 73 82 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. These included N133S, S147G (V1 region), N169D, K187E, S190N (V2 region), N237T, D282N, S294F (C2 region), A389T (V4 region), T437A (C4 region), and T463P (V5 region). 2020 Pathogens (Basel, Switzerland) Method HIV A389T;D282N;K187E;N133S;N169D;N237T;S147G;S190N;S294F;T437A;T463P 107;81;48;15;41;74;22;55;88;126;149 112;86;53;20;46;79;27;60;93;131;154 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. C8166 cells were infected with HIV-1A17, HIV-174V or HIV-1RF/V82F/184V, and PHA-stimulated PBMCs were incubated with HIV-1WAN or HIV-1TC-1 in RPMI-1640 at different serial dilutions of the compounds with a MOI of 0.1. 2020 Acta pharmaceutica Sinica. B Method HIV V82F 61 65 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. In addition, wild-type strains HIV-1IIIB and HIV-1Ba-L, and HIV-1 resistant strains HIV-1A17, HIV-174V and HIV-1RF/V82F/184V were obtained from the NIH AIDS Research and Reference Reagent Program (Bethesda, Maryland, ME, USA). 2020 Acta pharmaceutica Sinica. B Method HIV V82F 115 119 AIDS 152 156 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. The mixture was vortexed for 10 min at 750 rpm (Microporous Quick Shaker QB-9002, Changzhou, China) and centrifuged at 6000 rpm (Thermo Scientific Changzhou Multifuge X3R Centrifuge, Waltham, MA, USA) for 10 min. 2020 Acta pharmaceutica Sinica. B Method HIV X3R 167 170 Matrix 192 194 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. pET-11a vectors were used to express the HIV-1 capsid protein containing the A14C and E45C mutations. 2020 Cell reports Method HIV A14C;E45C 77;86 81;90 Capsid 47 53 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Point mutations P90A, A92E and G94D were introduced using the QuikChange II site-directed mutagenesis kit (Stratagene) according to the manufacturer's instructions. 2020 Cell reports Method HIV A92E;G94D;P90A 22;31;16 26;35;20 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Recombinant human immunodeficiency virus-1 (HIV-1) strains such as HIV-1-G89V, HIV-1-P90A, HIV-1-A92E and HIV-1-G94D expressing GFP and pseudotyped with VSV-G were prepared as previously described. 2020 Cell reports Method HIV A92E;G89V;G94D;P90A 97;73;112;85 101;77;116;89 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. This study generated the following new plasmids: pET11A-A14C/E45C/A92E, pET11A-A14C/E45C/G94D, HIV-1-P90A, HIV-1-G89V, HIV-1-A92E and HIV-1-G94D. 2020 Cell reports Method HIV A14C;A14C;A92E;E45C;E45C;G94D;A92E;G89V;G94D;P90A 56;79;66;61;84;89;125;113;140;101 60;83;70;65;88;93;129;117;144;105 32192810 Induction of cross-reactive HIV-1 specific antibody responses by engineered V1V2 immunogens with reduced conformational plasticity. Site-directed mutagenesis to introduce the K155M mutation in each was performed following the QuikChange site-directed mutagenesis protocol (Agilent). 2020 Vaccine Method HIV K155M 43 48 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. A database containing HIVDR profiles from 2412 individuals initiating first-line ART in Mexico City genotyped by MiSeq was used to select 60 plasma specimens enriched for mutations K65R, K103N/S, Y181C, M184V, and G190A. 2020 AIDS (London, England) Method HIV G190A;K103N;K103S;K65R;M184V;Y181C 214;187;187;181;203;196 219;194;194;185;208;201 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. OLA-Simple probes designed to detect K65R, K103N/S, Y181C, M184V, and G190A across multiple subtypes were modified to include polymorphisms observed frequently in pol sequences from individuals initiating an NNRTI/NRTI regimen in Mexico City between September 2017 and March 2018. 2020 AIDS (London, England) Method HIV G190A;K103N;K103S;K65R;M184V;Y181C 70;43;43;37;59;52 75;50;50;41;64;57 NNRTI;NRTI;Pol 208;214;163 213;218;166 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. As can be seen, the frequency of cluster sampling is stabilized from ~100 ns onwards in G40R and WT-free HIV-1 protease simulations (3 sets) and 130 ns onwards in G40E and Protease:RIT complex simulation, indicating equilibration of the MD trajectories. 2020 Scientific reports Method HIV G40E;G40R 163;88 167;92 PR;PR 111;172 119;180 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The residue glycine at position 40 in each monomer of HIV-1 protease was mutated to residue glutamate in G40E mutant and residue arginine in G40R mutant by using the mutation tool in the DeepView software. 2020 Scientific reports Method HIV G40E;G40R 105;141 109;145 PR 60 68 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The RMSD values and centre of mass (COM) distance between the monomers of protease for the G40E, G40R and WT-free HIV-1 protease are also stable throughout the simulation. 2020 Scientific reports Method HIV G40E;G40R 91;97 95;101 PR;PR 74;120 82;128 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. To build the initial structure of the mutants (G40E and G40R) of HIV-1 protease, the crystallographic structure of the wild-type HIV-1 protease (PDB ID: 1HXW) obtained from the Protein Data Bank (PDB) (www.rcsb.org) was taken as a reference. 2020 Scientific reports Method HIV G40E;G40R 47;56 52;60 PR;PR 71;135 79;143 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. To check the convergence of the trajectory of the G40E, G40R, Protease:RIT complex and 3 sets of WT-free HIV-1 protease, the variation of the sampling frequency of the first two most populated clusters was determined using gromos method, with respect to simulation time with an RMSD cut-off of 0.22 nm, 0.20 nm and 0.27 nm respectively. 2020 Scientific reports Method HIV G40E;G40R 50;56 54;60 PR;PR 62;111 70;119 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. The luciferase envelope-defective reporter proviral N74D plasmid was cloned from pLAI GFP3* N74D by BssHI and SalI digest and cloned into BruLuc2deltaEnv. 2020 PLoS pathogens Method HIV N74D;N74D 52;92 56;96 Env 15 23 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. The P90A CA mutation was introduced into pLAI GFP3 using standard cloning procedures as described previously. 2020 PLoS pathogens Method HIV P90A 4 8 Capsid 9 11 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. The pLAI GFP3* WT, pLAI GFP3* N74D, pLAI GFP3* A77V and pLAI GFP3* N57A proviruses were provided by Masahiro Yamashita and are described in. 2020 PLoS pathogens Method HIV A77V;N57A;N74D 47;67;30 51;71;34 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. All three isolates contain the L33F, M46I, and I84V major drug resistance mutations and the I13V accessory mutation. 2014 Discoveries (Craiova, Romania) Method HIV I13V;I84V;L33F;M46I 92;47;31;37 96;51;35;41 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Both E92Q and G140S mutations have been reported to reduce susceptibility of DTG ~1.5-fold and up to 10-fold respectively. 2020 PloS one Method HIV E92Q;G140S 5;14 9;19 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. For the WT system, 157 potassium ions (K) and 81 chloride ions (Cl) were added, for the mutant Y143R system we added 156 K and 81 Cl ions, while for the mutant system G140S we added 157 K and 81 Cl ions and for the mutant system E92Q we added 156 K and 81 Cl ions. 2020 PloS one Method HIV E92Q;G140S;Y143R 229;167;95 233;172;100 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The WT and three mutant systems (E92Q, G140S and Y143R) were prepared by uploading the atomic coordinates of the Protein-DNA-MG-DTG complexes to the CHARMM-GUI interface. 2020 PloS one Method HIV E92Q;G140S;Y143R 33;39;49 37;44;54 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). We compared the frequency of resistance mutations detected by next-generation sequencing and proviral bulk genotyping, and we analyzed the percentage of participants with M184V/I and/or K65R/E/N detected by next-generation sequencing at 1%, 5%, 10% and 20% thresholds at study entry. 2020 EBioMedicine Method HIV K65E;K65N;K65R;M184I;M184V 186;186;186;171;171 194;194;194;178;178 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. A G1313A Standard LC Autosampler (Agilent, Palo Alto, CA, USA) was used to collect samples for measurement of mass spectra. 2020 Acta pharmaceutica Sinica. B Method HIV G1313A 2 8 Capsid 54 56 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. The X-ray crystal structure of HIV-1 WT RT (PDB code: 6c0n), HIV-1 K103N RT (PDB code: 6c0o) and HIV-1 RES056 RT (PDB code: 6c0r), respectively corresponding to the X-ray crystallographic structure of the WT, K103N and RES056 RT in complex with the NNRTIs K-5a2 were chosen to build up the initial models for compound 26. 2020 Acta pharmaceutica Sinica. B Method HIV K103N 209 214 NNRTI;RT;RT;RT;RT 249;40;73;110;226 255;42;75;112;228 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. N348I) that may impact on ARV drug susceptibility. 2020 PloS one Method HIV N348I 0 5 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. The RT-associated RNase H activity of wt and mutated HIV RTs was measured as described, in 100 microL reaction volume containing 50 mM Tris HCl pH 7.8, 6-mM MgCl2, 1-mM dithiothreitol (DTT), 80-mM KCl, hybrid RNA/DNA (5'-GTTTTCTTTTCCCCCCTGAC-3'-fluorescein, 5'-CAAAAGAAAAGGGGGGACUG-3'-dabcyl, from Metabion, Planegg, Germany) and different amounts of enzymes according to a linear range of dose-response curve (60 ng of wt RT; 60 ng R448A RT; 160 ng R557A RT; 600 ng Q475A RT). 2020 Viruses Method HIV Q475A;R448A;R557A 467;433;450 472;438;455 RT;RT;RT;RT;RT;RT 4;57;423;439;456;473 6;60;425;441;458;475 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Triplicate wells of 96-well plates containing serial dilutions of drugs were seeded with 3 x 104 MT4 cells and infected with HIV-1 NL4.3 wt or with the HIV-1 NL4-3 K103N-Y181C strain at multiplicity of infection (MOI) of 0.003 or 100 culture infective dose (CCID50) calculated using the Reed and Muench method. 2020 Viruses Method HIV Y181C;K103N 170;164 175;169 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. Generation of Ld W97R Mutant Mouse by CRISPR/Cas9. 2020 Frontiers in immunology Method HIV W97R 17 21 Capsid 45 47 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. Ld W97R mutant mice were generated in our lab (described below). 2020 Frontiers in immunology Method HIV W97R 3 7 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Average transfection efficiencies were as follows: 33.7% for wildtype, 33.5% for H196Q, and 36.9% for H196Q / E191R with background fluorescence of approximately 4% in the untransfected control. 2020 PloS one Method HIV E191R;H196Q;H196Q 110;81;102 115;86;107 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. For CD4 downmodulation experiments, A66 cells were transfected with Nef variants (wildtype, H196Q, and H196Q / E191R) using the Amaxa 4D-Nucleofector Protocol with the CA-137 program and SF cell line reagent in 20 ul Nucleocuvette strips. 2020 PloS one Method HIV E191R;H196Q;H196Q 111;92;103 116;97;108 Nef;Capsid 68;168 71;170 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. To generate the H196Q mutation alone, we used the following mutagenesis primers using the QuikChange II Site-Directed Mutagenesis Kit (Agilent); F: GCA TTA TTT AAT GCA GCC AGC TCA AAC TTC CC, and R: GGG AAG TTT GAG CTG GCT GCA TTA AAT AAT GC and to generate the E191R mutation on the backbone that already contained the H196Q variant, we used the following mutagenesis primers; F: GGC ACA GGA GGA TGA GAG GCA TTA TTT AAT GCA GC, and R: GCT GCA TTA AAT AAT GCC TCT CAT CCT CCT GTG CC. 2020 PloS one Method HIV E191R;H196Q;H196Q 262;16;320 267;21;325 Gag;Gag 211;401 214;404 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The typical drugs that were available in public health facilities offering third line ART at the time of the study included the NNRTI etravarine (rilpivarine and doravarine were not yet available) and the NRTIs lamivudine and emtricitabine (for M184V mutations). 2020 PloS one Method HIV M184V 245 250 NNRTI;NRTI 128;205 133;210 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. At ~50% confluency, cells were infected with 2 ng (normalized for p27) of wild-type and Y44A Tat mutant HIV-2 pseudovirions, in 200 microL serum- and antibiotic-free media, supplemented with 8 microg/mL polybrene. 2020 International journal of molecular sciences Method HIV Y44A 88 92 Tat 93 96 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Dot-blotting of the cell lysate was performed as follows: GHOST(3) cells were transduced with 5 ng (normalized for p27) of wild-type or Y44A/Y55A mutant Tat HIV-2 pseudovirions as described previously. 2020 International journal of molecular sciences Method HIV Y44A;Y55A 136;141 140;145 Tat 153 156 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. In order to detect intracellularly expressed Tat and RT, cells were transfected with 10 microg of HIV-2 CGP plasmid coding for either the wild-type or Y44A mutant Tat. 2020 International journal of molecular sciences Method HIV Y44A 151 155 Tat;Tat;RT 45;163;53 48;166;55 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The following mutagenesis primers were used: Y44A_forward primer: 5'-CTC TCT CAG CTA GCC CGA CCC CTA GAA AC-3', Y44A_reverse primer: 5'-GT TTC TAG GGG TCG GGC TAG CTG AGA GAG-3'Y55A_forward primer: 5'-CA TGC AAT AAC TCA TGC GCC TGT AAG CGA TGC TGC TAC CAT TG-3', and Y55A_reverse primer: 5'-CA ATG GTA GCA GCA TCG CTT ACA GGC GCA TGA GTT ATT GCA TG-3'. 2020 International journal of molecular sciences Method HIV Y44A;Y44A;Y55A;Y55A 45;112;267;177 49;116;271;181 Capsid;Capsid 201;291 203;293 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. To generate the Y44A and Y55A mutations in HIV-2 Tat protein, HIV-2 tat gene, encoded by the HIV-2 CGP vector, was modified by site-directed mutagenesis using QuikChange Lightning Multi Site-Directed Mutagenesis Kit and QuikChange II XL Site-Directed Mutagenesis Kit (Agilent Technologies, Santa Clara, CA, USA), respectively. 2020 International journal of molecular sciences Method HIV Y44A;Y55A 16;25 20;29 Tat;Tat;Capsid 49;68;303 52;71;305 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. After refining the models using protein refinement tools, SIVcpzPtt MB897 Vif derivatives (M16E, M16A, M16D and M16Q) were generated based on the model of SIVcpzPtt MB897 Vif using Build Mutant protocol in Discovery Studio. 2020 PLoS pathogens Method HIV M16A;M16D;M16E;M16Q 97;103;91;112 101;107;95;116 Vif;Vif 74;171 77;174 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. The IMCs of SIVcpzPtt MB897 derivatives, M16E and E2X (vif-deleted) were generated by mutagenesis/overlap extension PCR using the primers listed in S4 Table. 2020 PLoS pathogens Method HIV E2X;M16E 50;41 53;45 Vif 55 58 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. The virus supernatant of SIVcpzPtt MB897 WT, M16E and E2X (vif-deleted) derivatives were inoculated into SupT11-CCR5 (parental) and SupT11-CCR5-gA3G cells at multiplicity of infection (MOI) 0.1. 2020 PLoS pathogens Method HIV E2X;M16E 54;45 57;49 Vif 59 62 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Although 1 participant who discontinued at week 4 because of physician decision was shown to have an RT V106I substitution, the virus remained susceptible to DOR. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV V106I 104 109 RT 101 103 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Among these, 5 isolates showed RT V106 (V106I, V106V/I, V106A, and V106M/T) substitutions in combination with one or more of A98A/G, H221H/Y, P225P/H, F227 (as F227C or F227C/R), or Y318Y/F RT substitutions, and 1 had genotypic resistance conferred through a Y188L substitution alone. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV A98A;A98G;F227C;F227C;F227R;H221H;H221Y;P225H;P225P;V106A;V106I;V106I;V106M;V106T;V106V;Y188L;Y318F;Y318Y 125;125;160;169;169;133;133;142;142;56;47;40;67;67;47;259;182;182 131;131;165;176;176;140;140;149;149;61;54;45;74;74;54;264;189;189 RT;RT 31;190 33;192 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Among those with PDVF who were tested, 2 DOR-treated participants developed resistance to DOR: 1 with RT V106I, H221Y, and F227C substitutions who discontinued at week 24 because of noncompliance and 1 with RT V106A/P225Y or V106A/P225H double substitution who was lost to follow-up after week 84. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV F227C;H221Y;P225H;P225Y;V106A;V106A;V106I 123;112;231;216;210;225;105 128;117;236;221;215;230;110 RT;RT 102;207 104;209 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. No phenotypic resistance to DOR was observed, but 1 isolate had RT E138E/G, V179D, and A62V substitutions and showed phenotypic resistance to EFV. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV A62V;E138E;E138G;V179D 87;67;67;76 91;74;74;81 RT 64 66 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. None of these participants had RT K103N, Y181C, or G190A substitutions at baseline. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV G190A;K103N;Y181C 51;34;41 56;39;46 RT 31 33 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Of the 4 participants who discontinued for other reasons and were tested, 1 who discontinued because of nonadherence exhibited viral resistance to DOR (RT V106I, H221Y, and F227C substitutions) and FTC (RT M184V). 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV F227C;H221Y;M184V;V106I 173;162;206;155 178;167;211;160 RT;RT 152;203 154;205 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. One isolate displayed the Y318Y/F DOR resistance-associated RT substitution but did not show phenotypic resistance. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV Y318F;Y318Y 26;26 33;33 RT 60 62 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. One participant who was nonadherent met PDVF criteria at week 24 and exhibited the RT G190A substitution; this participant also showed resistance to EFV and nevirapine at both baseline and time of PDVF (Tables 2 and 3). 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV G190A 86 91 RT 83 85 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Overall, 4% (n = 24/656) of participants entered the trial with RT K103N, Y181C, and/or G190A substitutions. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV G190A;K103N;Y181C 88;67;74 93;72;79 RT 64 66 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. The participant in the baseline group who received ritonavir-boosted darunavir, FTC, and TDF displayed an RT M184M/I substitution. 2020 Journal of acquired immune deficiency syndromes (1999) Method HIV M184I;M184M 109;109 116;116 RT 106 108 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The consensus sequence of the HIV-1 integrase of subtype B (UniProt accession code: B9VIC1) was used as reference to build the structure of the cSSC of each system (WT, N155H, and N155H+Q148H) through comparative modeling. 2020 Frontiers in molecular biosciences Method HIV N155H;N155H;Q148H 169;180;186 174;185;191 IN 36 45 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. A convenience sample of 100 patients that were seen at the clinic between 1 September 2014 and 31 August 2017 were included in the study if they were HIV-infected, 18-89 years of age, on ART, and with at least an M184V/I mutation documented via genotypic resistance tests. 2020 SAGE open medicine Method HIV M184I;M184V 213;213 220;220 HIV infections 150 162 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Both 3TC and FTC were assigned a GSS of 0 in the presence of an M184V/I mutation. 2020 SAGE open medicine Method HIV M184I;M184V 64;64 71;71 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. The Pol S653A, S653T, S653L, S653K, or S653Q mutation was inserted into the 93JP-NH1 plasmid containing a Pol region between ApaI and Af1II sites. 2021 AIDS (London, England) Method HIV S653A;S653K;S653L;S653Q;S653T 8;29;22;39;15 13;34;27;44;20 Pol;Pol 4;106 7;109 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Media containing VSV-G pseudotyped lentiviral vectors expressing HIV1 WT or HIV1-P90A or N-MLV was added to infect cells in a total volume of 100 muL in the presence of polybrene. 2020 PLoS pathogens Method HIV P90A 81 85 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. THP1 control and the different THP1 KO cells were seeded into 96 well plates at a density of 50000 cells/well, differentiated with PMA, then primed with VSV-G pseudotyped HIV-mCherry (at a CrFK MOI of 3) or VSV-G pseudotyped HIV-mCherry CA P90A (at a CrFK MOI of 3) or VSV-G pseudotyped N-MLV-mCherry (at a CrFK MOI of 0.5), 24h later media was removed, washed and challenged with different dilutions of VSV-G pseudotyped HIV1-WT-GFP tagged (CrFK MOI of 2 was used as the starting dilution). 2020 PLoS pathogens Method HIV P90A 240 244 Capsid 237 239 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Three part, single cycle VSV-G-pseudotyped N-MLV, HIV1 WT and recombinant HIV-1 strain (HIV-1 CA P90A) were produced by co-transfecting 15 mug lentivector genome plasmid (pLVX-mcherry), 10 mug gag-pol plasmid (pCIG3-N for N-MLV, WT and P90A HIV-1 capsid; kindly provided by Edward Campbell) and 5 mug VSV-G plasmid. 2020 PLoS pathogens Method HIV P90A;P90A 97;236 101;240 GagPol;Capsid;Capsid 193;247;94 200;253;96 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. Key exclusion criteria included presence of NRTI resistance mutations K65R, T69 insertion, K70E, or Q151M mutation complex and any primary integrase strand transfer inhibitor or protease inhibitor (PI) resistance mutations. 2021 Journal of acquired immune deficiency syndromes (1999) Method HIV K65R;K70E;Q151M 70;91;100 74;95;105 IN;PR;NRTI;PI 139;178;44;198 148;186;48;200 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. Participants were adults with HIV and virologic suppression (HIV-1 RNA <50 copies per milliliter for >=6 months before screening, measured at least twice using the same assay) who received a stable antiretroviral regimen (for >=6 consecutive months before screening) containing FTC/TDF or ABC/3TC plus an allowed antiretroviral agent with documented M184V and/or M184I mutations (based on historical plasma genotypic assays [by Sanger sequencing]), without (part 1) or with/without (part 2) 1 or 2 thymidine analog-associated mutations (TAMs). 2021 Journal of acquired immune deficiency syndromes (1999) Method HIV M184I;M184V 363;350 368;355 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. As in a previous paper from START reporting the results of locally performed Sanger sequencing, TDR was based on the WHO 2009 surveillance list with the addition of RT mutations T215N and E138K. 2021 HIV medicine Method HIV E138K;T215N 188;178 193;183 RT 165 167 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. INSTI mutations, which are not included on this list, were defined as those on the Stanford HIVdb surveillance DRM list, namely T66AIK, E92Q, F121Y, G140ACS, Y143CHR, S147G, Q148HKR and N155HS. 2021 HIV medicine Method HIV E92Q;F121Y;G140A;G140C;G140S;N155H;N155S;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;Y143C;Y143H;Y143R 136;142;149;149;149;186;186;174;174;174;167;128;128;128;158;158;158 140;147;156;156;156;192;192;181;181;181;172;134;134;134;165;165;165 INSTI 0 5 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. A single subunit of the MA-CA-SP1 was subsequently used to refine interactions with the G123E mutant, whereas two adjacent subunits were used for interactions with the H219Q mutant. 2021 Computational and structural biotechnology journal Method HIV G123E;H219Q 88;168 93;173 SP1;Matrix;Capsid 30;24;27 33;26;29 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Atomistic MD simulations were performed to understand the role of the H219Q mutations on CypA binding and Q199H on CA oligomerisation. 2021 Computational and structural biotechnology journal Method HIV H219Q;Q199H 70;106 75;111 Capsid 115 117 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Double mutants E138K/M184I and E138K/M184V were prepared from the single-mutant E138K HIV-1 RT, previously described. 2021 Viruses Method HIV E138K;E138K;E138K;M184I;M184V 15;31;80;21;37 20;36;85;26;42 RT 92 94 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Mutant G344E/D345P/ins346F of HIV-2EHO RT was prepared with mutagenic oligonucleotides containing the nucleotide changes required to introduce G344E and D345P substitutions in the presence of the insertion of Phe346, and the template RT-coding region encoding the HIV-2EHO RT with the 346F insertion alone. 2021 Viruses Method HIV D345P;G344E;D345P;G344E 13;7;153;143 18;12;158;148 RT;RT;RT 39;234;273 41;236;275 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Quadruple mutants E138K/M184I/N348I/T369I and E138K/M184V/N348I/T369I were obtained after introducing mutations E138K and M184I/V in sequential order, using as template the plasmid p66RTB containing the p66-coding sequence of mutant N348I/T369I HIV-1BH10 RT. 2021 Viruses Method HIV E138K;E138K;M184I;M184V;N348I;N348I;T369I;T369I;E138K;M184I;M184V;N348I;T369I 18;46;24;52;30;58;36;64;112;122;122;233;239 23;51;29;57;35;63;41;69;117;129;129;238;244 RT 255 257 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The mutant H342Y/G344E/D345P/ins346F/V351T was derived from mutant G344E/D345P/ins346F, after introducing mutations H342Y and V351T in sequential order with the mutagenic primers indicated in the Supplementary Table S1. 2021 Viruses Method HIV D345P;D345P;G344E;G344E;H342Y;V351T;H342Y;V351T 23;73;17;67;11;37;116;126 28;78;22;72;16;42;121;131 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. WT HIV-1BH10 RT and mutants N348I and N348I/T369I and HIV-1 group O RTs (WT HIV-1ESP49 RT and mutant T355A/Q357M/K358R/A359G/S360A (5M)) were obtained as heterodimers composed of subunits of 66 and 51 kDa, containing poly-histidine tags at the C-terminus of p66. 2021 Viruses Method HIV A359G;K358R;Q357M;S360A;T355A;N348I;N348I;T369I 119;113;107;125;101;28;38;44 124;118;112;130;106;33;43;49 RT;RT;RT 13;68;87 15;71;89 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The A45E, T70R, Q63R and L75G MA mutant constructs were generated using a QuickChange Lightning site-directed mutagenesis kit (Agilent Technologies). 2021 The Journal of biological chemistry Method HIV A45E;L75G;Q63R;T70R 4;25;16;10 8;29;20;14 Matrix 30 32 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The HIV-1 myr(-)MA Q63R protein used in the crystallization trials was at 20 mg/ml in a buffer containing 10 mM Tris.HCl (pH 8), 1 mM EDTA, 2 mM beta-mercaptoethanol, and 50 mM NaCl. 2021 The Journal of biological chemistry Method HIV Q63R 19 23 Matrix 16 18 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Briefly, CA structures were self-assembled using a mixture of CA A204C/A92E (for cross-linking and increased solubility, respectively) and AF647-labelled CA K158C and then captured on the surface of a coverslip. 2021 PLoS pathogens Method HIV A204C;A92E;K158C 65;71;157 70;75;162 Capsid;Capsid;Capsid 9;62;154 11;64;156 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Plasmid pET11a bearing HIV-1 CA pentamer mutant (N21C/A22C/W184A/MA815A) was transformed into E. 2021 PLoS pathogens Method HIV A22C;N21C;W184A 54;49;59 58;53;64 Matrix;Capsid 65;29 67;31 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. A combination of C90A/C306A/H547A was generated as E2C/H547A hDAT for MTSET-insensitive control for H547A. 2021 Journal of neuroimmune pharmacology Method HIV C306A;C90A;H547A;H547A;H547A 22;17;28;55;100 27;21;33;60;105 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. A triple mutation of the two cysteine90 and 306 residues to alanine and aspartic acid151 to cysteine on WT hDAT was generated as E2C-I159C hDAT (C90A/C306A/I159C) for MTSET-sensitive construct. 2021 Journal of neuroimmune pharmacology Method HIV C306A;C90A;I159C;D151C;E2C;I159C 150;145;156;72;129;133 155;149;161;100;132;138 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. HEK293 cells were grown in poly-d-lysine coated plates at a density of 1 x 105 cells/cm2 were transfected with different E2C-associated hDAT background constructs: E2C hDAT, E2C-I159C hDAT, E2C/H547A hDAT, E2C-I159C/H547A or E2C-I159A/H547A. 2021 Journal of neuroimmune pharmacology Method HIV E2C;E2C;E2C;H547A;H547A;H547A;I159A;I159C;I159C 121;164;174;194;216;235;229;178;210 124;167;177;199;221;240;234;183;215 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. In addition, the combination of mutations on Tyr88, Asp206, and His547 (tyrosine88 to phenylalanine and aspartic acid 206 to leucine and histidine 547 to alanine, Y88F/D206L/H547A) were predicted to eliminate three hydrogen bonds from the Tat-hDAT complex. 2021 Journal of neuroimmune pharmacology Method HIV D206L;H547A;Y88F;D206L;H547A;Y88F 168;174;163;104;137;72 173;179;167;132;161;100 Tat;Asp 239;52 242;55 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Intact PC12 cells in 24-well plates transiently expressing WT hDAT or H547A were washed twice with 1x KRH buffer. 2021 Journal of neuroimmune pharmacology Method HIV H547A 70 75 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Previous studies show 0.5 mM MTSET for 10 min exhibiting a 40 % inhibition on E2C-I159C. 2021 Journal of neuroimmune pharmacology Method HIV E2C;I159C 78;82 81;87 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Recombinant HIV-1 transactivator of transcription (Tat1-86, REP0002a) protein and its mutant Tat protein at cysteine22 residue (substituted to glycine, C22G) and at lysine19 residue (substituted to alanine, K19A) were purchased from Diatheva (Fano, Italy). 2021 Journal of neuroimmune pharmacology Method HIV C22G;K19A 152;207 156;211 Tat;Tat 51;93 54;96 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The combination of hDAT mutations on Asp206 and His547 (Aspartic acid 206 to leucine and histidine 547 to alanine, D206L/H547A) were predicted to eliminate two hydrogen bonds between Tat and hDAT. 2021 Journal of neuroimmune pharmacology Method HIV D206L;D206L;H547A;H547A 115;56;121;89 120;85;126;113 Tat;Asp 183;37 186;40 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. To determine whether H547A-enhanced DA transport is mediated by changing transporter conformation, two combinations of C90A/C306A/I159C/H547A and C90A/C306A/I159A/H547A were generated as E2C-I159C/H547A and E2C-I159A/H547A for positive and negative controls for MTSET sensitive background, respectively. 2021 Journal of neuroimmune pharmacology Method HIV C306A;C306A;C90A;C90A;H547A;H547A;I159A;I159C;H547A;H547A;H547A;I159A;I159C 124;151;119;146;136;163;157;130;21;197;217;211;191 129;156;123;150;141;168;162;135;26;202;222;216;196 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. To determine whether the H547A-induced increase in Vmax was due to a palmitoylation-mediated mechanism, kinetic analysis of [3H]DA uptake in WT hDAT and H547A was performed in the presence or absence of 15 muM 2-BP, a palmitoylation inhibitor. 2021 Journal of neuroimmune pharmacology Method HIV H547A;H547A 25;153 30;158 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Two extracellular cysteine90 and cysteine306 residues on WT hDAT were mutated to alanine as E2C hDAT (C90A/C306A hDAT), rendering the E2C hDAT MTSET-insensitive background. 2021 Journal of neuroimmune pharmacology Method HIV C306A;C90A;E2C;E2C 107;102;92;134 112;106;95;137 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Inclusion criteria included vertically HIV-infected youths and young adults aged 10 years and older at patient selection time, under ART and virologically suppressed with HIV-1 RNA <50 copies/mL for >=1 year before sampling, lamivudine-and/or emtricitabine-experienced, and carrying M184V/I and/or K65R/E/N in their historic plasma samples, as indicated in Figure 1. 2021 The Journal of antimicrobial chemotherapy Method HIV K65E;K65N;K65R;M184I;M184V 298;298;298;283;283 306;306;306;290;290 HIV infections 39 51 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. The presence of M184V/I and K65R/E/N was analysed by the HIVdb Program Genotypic Resistance Interpretation Algorithm v8.9-1 (Stanford University, USA). 2021 The Journal of antimicrobial chemotherapy Method HIV K65E;K65N;K65R;M184I;M184V 28;28;28;16;16 36;36;36;23;23 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. To analyse the prevalence of resistance changes M184V/I and/or K65R/E/N to lamivudine and emtricitabine in pDNA of study population, genomic DNA was extracted from available PBMCs obtained from the Spanish HIV BioBank using QIAamp DNA Blood Mini Kit (QIAGEN) according to manufacturer's protocol. 2021 The Journal of antimicrobial chemotherapy Method HIV K65E;K65N;K65R;M184I;M184V 63;63;63;48;48 71;71;71;55;55 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. We considered three timepoints: point 1 referred to the collection time of historic plasma carrying M184V; point PBMCs referred to PBMCs sampling time; and 31 December 2019 was the last evaluation. 2021 The Journal of antimicrobial chemotherapy Method HIV M184V 100 105 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The S163C, R178G and double mutants were created from NL4-3 Nef with site-directed mutagenesis. 2021 Viruses Method HIV R178G;S163C 11;4 16;9 Nef 60 63 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. AS-PCR was performed using primers IN_K65_fw (5'-TCCAGTATTTGCCATAAAGIA-3') or IN_K65R_fw (5'-CCAGTATTTGCCATAAAGIG-3'), and pol_3206_rv (5'-TTTGTCTGGTGTGGTAAATCCCCAC-3'). 2021 Viruses Method HIV K65R 81 85 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. Based on viral copy numbers of each variant, the replication capacity percentages were calculated to determine the competition kinetics of HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V. 2021 Viruses Method HIV K65R;M184V 170;175 174;180 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. For the dual-competition infections, HIV-1 JR-CSFWT was combined with HIV-1 JR-CSFK65R_M184V at a 1:1 ratio for a combined MOI of 0.001 and added to 2 x 106 mixed donor, 3-way stimulated, CD8-depleted PBMCs. 2021 Viruses Method HIV M184V 87 92 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. For the parallel infections, HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V, were added separately to tubes containing 2 x 106 mixed donor, 3-way stimulated, CD8-depleted PBMCs. 2021 Viruses Method HIV M184V 65 70 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. HEK293T cells were transfected with mixtures containing serum-free DMEM (no FBS, no PenStrep), 25 microg of plasmid (pJR-CSFWT or pJR-CSFK65R_M184V) and 2 microg of polyethylenimine (PEI) per microg of DNA. 2021 Viruses Method HIV M184V 142 147 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. In addition, for dual-competition infection data acquisition, the viral copy numbers of HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V in the mixtures were separately measured with allele-specific polymerase chain reaction (AS-PCR). 2021 Viruses Method HIV M184V 124 129 Pol 192 202 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. The K65R and M184V mutations were introduced into the pJR-CSFWT plasmid using the QuikChange XL Site-Directed Mutagenesis Kit (Agilent Technologies, Inc., Santa Clara, CA, USA) with sdm_M184V_fw (5'-CCAGACATAATTATCTATCAATACGTGGATGATTTGTATGTAGGATCTG-3'), sdm_M184V_rv (5'-CAGATCCTACATACAAATCATCCACGTATTGATAGATAATTATGTCTGG-3'), sdm_K65R_fw (5'-CTCCAGTATTTGCCATAAAGAGAAAAGACAGTACTAAATGGAG-3') and sdm_K65R_rv (5'-CTCCATTTAGTACTGTCTTTTCTCTTTATGGCAAATACTGGAG-3'), following the manufacturer's protocol. 2021 Viruses Method HIV K65R;K65R;K65R;M184V;M184V;M184V 4;330;398;13;186;258 8;334;402;18;191;263 Capsid 168 170 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. The validity of the K65R_M184V AS-PCR protocol was evaluated and confirmed as previously described. 2021 Viruses Method HIV M184V 25 30 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. To evaluate parallel and dual competition infections, the viral titers were determined for HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V and were used to calculate the amount of virus stock required for a multiplicity of infection (MOI) of 0.001. 2021 Viruses Method HIV M184V 127 132 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. The mutations of interest included: T66A/I/K, E92Q, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H and R263K. 2021 Viruses Method HIV E138A;E138K;E138T;E92Q;G118R;G140A;G140C;G140S;N155H;Q148H;Q148K;Q148R;R263K;S147G;T66A;T66I;T66K;Y143C;Y143H;Y143R 59;59;59;46;52;70;70;70;110;99;99;99;120;92;36;36;36;81;81;81 68;68;68;50;57;79;79;79;115;108;108;108;125;97;44;44;44;90;90;90 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Briefly, HEK-293T cells were transfected with HIV-1 DNAs (HIV-1 subtype B clone NL4-3 WT, HIV-1 subtype C clone K3016 WT and its mutants SP1: A1V CA:I201V, SP1:N9S, SP1:G10T and SP1:N9S/G10T, HIV-1 subtype C clone IndieC1 WT and its mutants SP1:S9N, SP1:T10G, and SP1:S9N/T10G, HIV-1 subtype C clone ZM247 WT and its mutants SP1:S9N, SP1:T10G and SP1:S9N/T10G), as mentioned above. 2021 Retrovirology Method HIV A1V;G10T;I201V;T10G;T10G;N9S;S9N;S9N 142;186;149;272;355;182;268;351 145;190;154;276;359;185;271;354 SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;Capsid 137;156;165;178;241;250;264;325;334;347;146 140;159;168;181;244;253;267;328;337;350;148 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. HEK-293 T cells were transfected with HIV-1 DNAs (HIV-1 subtype B clone NL4-3, HIV-1 subtype C clone K3016 WT and its mutants SP1: A1V, SP1:I201V, SP1:N9S, SP1:G10T, SP1:N9S/G10T, HIV-1 subtype C clone IndieC1 WT and its mutants SP1:S9N, SP1:T10G, SP1:S9N/T10G, HIV-1 subtype C clone ZM247 WT and its mutants SP1:S9N, ZM247 SP1:T10G, ZM247 SP1:S9N/T10G) (3 microg) using Lipofectamine 2000 (Invitrogen catalog number: 11668-019) following manufacturer's recommendations, whereas HUT-R5 T-cells were transfected with HIV-1 DNAs using DEAE-dextran as described previously. 2021 Retrovirology Method HIV A1V;G10T;T10G;T10G;N9S;S9N;S9N 131;174;256;348;170;252;344 134;178;260;352;173;255;347 SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1 126;136;147;156;166;229;238;248;309;324;340 129;139;150;159;169;232;241;251;312;327;343 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. HEK-293T cells were transfected K3016 WT or its mutants-SP1:N9S, SP1:G10T, SP1:N9S/G10T, IndieC1 WT or its mutants- SP1:S9N, SP1:T10G, SP1:S9N/T10G, ZM247 WT or its mutants-SP1:S9N, SP1:T10G, SP1:S9N/T10G, and cultured in the presence of serial dilution of the BVM analog. 2021 Retrovirology Method HIV G10T;T10G;T10G;N9S;S9N;S9N 83;143;200;79;139;196 87;147;204;82;142;199 SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1 56;65;75;116;125;135;173;182;192 59;68;78;119;128;138;176;185;195 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. HEK-293T cells were transfected with HIV-1 DNAs (HIV-1 subtype B clone NL4-3, HIV-1 subtype C clone K3016 WT and its mutants SP1: A1V, SP1:I201V, SP1:N9S, SP1:G10T, SP1:N9S/G10T, HIV-1 subtype C clone IndieC1 WT, and its mutants SP1:S9N, SP1:T10G, SP1:S9N/T10G, HIV-1 subtype C clone ZM247 WT, and its mutants SP1:S9N, SP1:T10G, SP1:S9N/T10G as mentioned above. 2021 Retrovirology Method HIV A1V;G10T;T10G;T10G;N9S;S9N;S9N 130;173;256;337;169;252;333 133;177;260;341;172;255;336 SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1 125;135;146;155;165;229;238;248;310;319;329 128;138;149;158;168;232;241;251;313;322;332 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Synthetic complementary oligonucleotides used were: K3016 SP1: A1V; 5'-GGCAAGGGTGTTGGTTGAGGCAATGAGCC-3', K3016 CA: I201V; 5'-GCGAACCCAGATTGTAAGATCGTTTTAAGAGGATTAGGACC-3', K3016 SP1:N9S 5'-GCTGAGGCAATGAGCCAAGCAAACAGTGGAAACATAATG-3',K3016 SP1: G10T 5'-CTCTGCATCATTATGTTTGTATTGTTTGCTTGGCTCATTGCCTC-3', K3016 SP1: N9S/G10T 5'-GGCAATGAGCCAAGCAAACAGTACAAACATAATGATGCAGA-3', IndieC1 SP1: S9N 5'-CAATGAGCCAAGCAAACAATACCATACTGATGCAGAG-3', IndieC1 SP1: T10G 5'-GCTTCTCTGCATCAGTATGCCACTGTTTGCTTGGCTCATT-3', IndieC1 SP1: S9N/G10T 5'-TGAGGCAATGAGCCAAGCAAACAATGGCATACTGAT-3', ZM247 SP1: S9N 5'-GCAATGAGCCAAGCAAACAACACAAACATAATGATGCAG-3', ZM247 SP1: T10G 5'-TTTCTCTGCATCATTATGTTTCCGCTGTTTGCTTGGCTCATTGC-3', ZM247 SP1: S9N/T10G 5'-GCTGAGGCAATGAGCCAAGCAAACAACGGAAACATAATG-3'. 2021 Retrovirology Method HIV A1V;G10T;G10T;G10T;I201V;N9S;S9N;S9N;S9N;S9N;T10G;T10G;T10G 63;242;314;513;115;310;381;509;573;703;443;635;707 66;246;318;517;120;313;384;512;576;706;447;639;711 SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;SP1;Capsid 58;177;237;305;376;438;504;568;630;698;111 61;180;240;308;379;441;507;571;633;701;113 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. For kinetic analysis of Gag WT and T8I cleavage, 3.3 muM of HIV-1 PR was added to the Gag assembly mixture and incubated at 37 C, at different time points, 4ul of the digestion reaction mixture was taken out and mixed with NuPAGE LDS Sample Buffer (Invitrogen) to stop the reaction, and then subjected to NuPAGE Novex 4-12% Bis-Tris gel (Invitrogen) for cleavage products analysis and visualized by Coomassie blue staining. 2021 Communications biology Method HIV T8I 35 38 Gag;Gag;PR 24;86;66 27;89;68 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. PR digestion experiments with recombinant WT and T8I assemblies were performed by the addition of various concentrations of PR to the Gag WT assembly mixture and T8I cell lysate which was pre-treated and diluted to 2 mg/ml, and incubated at 37 C for 2 h. 2021 Communications biology Method HIV T8I;T8I 49;162 52;165 Gag;PR;PR 134;0;124 137;2;126 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Patients with the following baseline mutations associated with reduced susceptibility to DTG: T66K, E92Q, G118R, E138 K/A/T, G140 S/A/C, Q148 H/R/K, N155H and R263K were excluded. 2021 AIDS research and therapy Method HIV E138A;E138K;E92Q;G118R;G140A;G140S;N155H;Q148H;Q148R;R263K;T66K 113;113;100;106;125;125;149;137;137;159;94 123;123;104;111;135;135;154;147;147;164;98 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. As of fact, the mutation V75VI often occurs along with the multi-resistance Q151M, but when alone its clinical significance is uncertain so was not considered in the definition of drug resistance (http://hivdb.stanford.edu). 2021 Infectious diseases Method HIV Q151M;V75I;V75V 76;25;25 81;30;30 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. In samples collected between 2014 and 2015, the following mutations were detected in the main cohort; K103N, G190A and L90M . 2020 AAS open research Method HIV G190A;K103N;L90M 109;102;119 114;107;123 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. PANDAA qPCR reactions for detecting drug-resistant point mutations K103N, M184V, V106M were performed on an ABI 7500 real-time PCR System (Applied Biosystems). 2020 AAS open research Method HIV K103N;M184V;V106M 67;74;81 72;79;86 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. The different protocols (K103N, V106M and M184V) were performed separately, each with a corresponding set of standards. 2020 AAS open research Method HIV K103N;M184V;V106M 25;42;32 30;47;37 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The anti-HIV-1 activity of PF74 and ZW-1261 against the WT and M66I HIV-1 viruses was examined in TZM-GFP cells. 2021 Viruses Method HIV M66I 63 67 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The FEP+ program from the Schrodinger Suite 2020-4 was also used to calculate the relative binding free energies of the wild-type and mutant M66I. 2021 Viruses Method HIV M66I 141 145 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The metadynamics module implemented in the Desmond software package was used to explore the complex free-energy surface of thedihedral of the I66 in the apo structure of the M66I mutant. 2021 Viruses Method HIV M66I 174 178 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The mutation M66I in the capsid region was introduced into this vector by site-directed mutagenesis. 2021 Viruses Method HIV M66I 13 17 Capsid 25 31 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The structure of the M66I-GS-6207 complex corresponded to the final state () of the FEP simulation. 2021 Viruses Method HIV M66I 21 25 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The structure of the M66I-GS-6207 complex used in the MD simulation in Figure 5 was obtained from FEP simulations using the FEP+ program from the Schrodinger Suite that mutated MET66 into ILE. 2021 Viruses Method HIV M66I;M66I 21;177 25;191 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Twenty-four hours post treatment, cells were exposed to WT or M66I HIV-1 (Multiplicity Of Infection (MOI) = 1). 2021 Viruses Method HIV M66I 62 66 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. WT and M66I HIV-1NL4-3 viruses were generated by transfecting HEK 293FT cells in a T75 flask with 10 microg of the pNL4-3 vector and FuGENE HD Transfection Reagent (Promega, Madison, WI, USA). 2021 Viruses Method HIV M66I 7 11 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. T215 mutations other than T215Y/F were called T215 revertants because they often emerge in individuals initially infected with a virus containing T215Y/F. 2021 Viruses Method HIV T215F;T215F;T215Y;T215Y 26;146;26;146 33;153;33;153 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Tenofovir-associated mutations were defined as A62V, K65R/N/E, S68G/N/D, T69 deletions, and K70E/Q/N/T/S/G. 2021 Viruses Method HIV A62V;K65E;K65N;K65R;K70E;K70G;K70N;K70Q;K70S;K70T;S68D;S68G;S68N 47;53;53;53;92;92;92;92;92;92;63;63;63 51;61;61;61;106;106;106;106;106;106;71;71;71 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Thymidine-analog mutations were defined as the NRTI-SDRMs M41L, D67N/G/E, K70R, L210W, T215Y/F/S/C/D/E/I/V, and K219Q/E/N/R. 2021 Viruses Method HIV D67E;D67G;D67N;K219E;K219N;K219Q;K219R;K70R;L210W;M41L;T215C;T215D;T215E;T215F;T215I;T215S;T215V;T215Y 64;64;64;112;112;112;112;74;80;58;87;87;87;87;87;87;87;87 72;72;72;123;123;123;123;78;85;62;106;106;106;106;106;106;106;106 NRTI 47 51 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. All sequences having the K65R were separated by subtype and used to query local and public databases to identify highly related HIV-1 sequences. 2021 International journal of molecular sciences Method HIV K65R 25 29 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Minimum spanning network analysis of the sequences identified in transmission clusters with more than one K65R mutant was performed with PHYLOViZ. 2021 International journal of molecular sciences Method HIV K65R 106 110 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Phylogenetic Analysis of K65R Sequences and Transmission Clusters. 2021 International journal of molecular sciences Method HIV K65R 25 29 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. The wildtype sequence (NPYNTPVFAIKKKDSTKWRKLVD) and the sequence with the K65R mutation (NPYNTPVFAIKRKDSTKWRKLVD) were used to generate all possible peptides sequences overlapping position 65 and ranging from eight to 12 amino acids. 2021 International journal of molecular sciences Method HIV K65R 74 78 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. In the final analyses we have also included the L74M integrase polymorphism as included in the IAS 2019 drug resistance update. 2021 Scientific reports Method HIV L74M 48 52 IN 53 62 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. A T332N mutation was introduced into BG505 Env to produce the BG505.T332N clone. 2021 mBio Method HIV T332N;T332N 2;68 7;73 Env 43 46 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Fusion peptide (FP) probes were created by fusing the FP motif, AVGIGAVFL, to an FR or 1TD0 subunit with a 5GS (G4S) linker. 2021 mBio Method HIV G4S 112 115 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Other BG505.T332N mutants were created by introducing mutations as previously described. 2021 mBio Method HIV T332N 12 17 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Raltegravir-resistant IN_a variants with two patterns of primary resistance to RAL: L74M, E92Q, V151I, N155H, G163R (IN_a_r1) and E138K, G140S, Q148K (IN_a_r2), and their variants inactivated by mutation D64V (IN_in_r1 and IN_in_r2) were generated by site-directed mutagenesis of pETIN_a using the QuikChange II Site-Directed Mutagenesis kit (Agilent Technologies, Santa Clara, CA, USA) with generation of plasmids pETIN_a_r1, pETIN_a_r2, pETIN_in_r1, and pETIN_in_r2, respectively. 2021 Microorganisms Method HIV D64V;E138K;E92Q;G140S;G163R;L74M;N155H;Q148K;V151I 204;130;90;137;110;84;103;144;96 208;135;94;142;115;88;108;149;101 Capsid 378 380 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. The pol region was amplified by nested PCR with initial primer G17S (AAAAAGGGCTGTTGTTGGTGGAATGTGGA)/MMRTR6 (TTTTACATTAGTGTGGG) and MMRTR5 (TAAATTTGATATGTCCATTG)/MMRT10 (CAGGCTAATTTTTTAGGGAA) generating a final fragment of 1478 bp (positions 2077-3574 relative to HXB2). 2021 BioMed research international Method HIV G17S 63 67 Pol 4 7 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. HIV-1 IN CCD (F185H) Expression, Purification, Crystallization, and X-ray Crystallography. 2021 PLoS pathogens Method HIV F185H 14 19 IN 6 8 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. p89.6 plasmid was applied for Quickchange kit (Invitrogen) to create Y99H single, A128T single, Y99H/A128T double mutants as well as two natural variants (A124N and T125A), and these 89.6 variant viruses were generated by transfecting 293T cells and culturing the produced viruses in CEMx174 cells. 2021 PLoS pathogens Method HIV A124N;A128T;A128T;T125A;Y99H;Y99H 155;82;101;165;69;96 161;87;106;170;73;100 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Passages 4 and 14 viral supernatant collected were selected to illustrate the effect of single mutation (Y99H, passage 4) and double mutations (Y99H and A128T). 2021 PLoS pathogens Method HIV A128T;Y99H;Y99H 153;105;144 158;109;149 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. The HIV-1 IN CCD (residues 50-212) containing the F185H mutation was expressed and purified as described. 2021 PLoS pathogens Method HIV F185H 50 55 IN 10 12 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. The role of any non-TAM was not specifically studied because of the low number of patients harboring the K65R/E/N mutation (the only other non-TAM associated with decreased susceptibility to 3TC) and its collinearity with M184V/I. 2021 Open forum infectious diseases Method HIV K65E;K65N;K65R;M184I;M184V 105;105;105;222;222 113;113;113;229;229 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. The variables expressing NRTI RAMs were identified as follows: (1) presence versus absence of any NRTI RAM; (2) presence versus absence of at least 1 TAM (M41L, D67N, K70R, L210W, T215Y/F, K219Q/E); (3) presence versus absence of M184V/I (with or without other RAMs); (4) presence versus absence of M184V/I not associated with TAMs; (5) presence versus absence of M184V/I combined with at least 1 TAM. 2021 Open forum infectious diseases Method HIV D67N;K219E;K219Q;K70R;L210W;M184I;M184I;M184I;M184V;M184V;M184V;M41L;T215F;T215Y 161;189;189;167;173;230;299;364;230;299;364;155;180;180 165;196;196;171;178;237;306;371;237;306;371;159;187;187 NRTI;NRTI 25;98 29;102 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. Participants had an estimated glomerular filtration rate (eGFR) >=50 mL per minute (calculated by the Cockcroft-Gault equation) and no documented history of resistance to INSTIs or tenofovir (TFV) resistance defined as K65R/E/N mutations, >=3 thymidine analog mutations, or T69 insertions (See Appendix, Supplemental Digital Content, http://links.lww.com/QAI/B674). 2021 Journal of acquired immune deficiency syndromes (1999) Method HIV K65E;K65N;K65R 219;219;219 227;227;227 INSTI 171 177 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. We performed subgroup analyses of the participants with plasma HIV-1 RNA <50 copies/mL at week 24 based on age, sex, baseline NRTI resistance, and specifically baseline M184V/I resistance. 2021 Journal of acquired immune deficiency syndromes (1999) Method HIV M184I;M184V 169;169 176;176 NRTI 126 130 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Images were acquired every 1 min for 90 min using a 60X RING-TIR-FM objective (Olympus Apo N 60X 1.49 Oil) with an exposure time of 100 ms, 10% Transmission A488 nm laser. 2021 Retrovirology Method HIV N60X 91 96 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Primers used for mutagenesis include: K359A F: 5'-CCGGCCATGCTGCAAGAGTTTTG; K359A R: 5'-CAAAACTCTTGCAGCATGGCCGG; T371I F: 5'-GCAATGAGCCAAGTAATAAATCCAGCTACC; T371I R: 5'-GGTAGCTGGATTTATTACTTGGCTCATTGC; P289S F: 5'-CATAAGACAAGGAAGTAAGGAACCCTTTAGAG; P289S R: 5'-CTCTAAAGGGTTCCTTACTTCCTTGTCTTATG; R57G F: 5'-TCAAAGTAGGACAGTATGATC; R57G R: 5'-GATCATACTGTCCTACTTTGA. 2021 Retrovirology Method HIV K359A;K359A;P289S;P289S;R57G;R57G;T371I;T371I 38;75;200;246;292;326;112;156 43;80;205;251;296;330;117;161 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. WT control or IPMK KO 293T cells were seeded at 2.5 x 105 cells/well in a 24 well plate and transfected with 625 ng of HIV-1WT, HIV-1K359A, or HIV-1K359A/T371I proviral plamids. 2021 Retrovirology Method HIV T371I 154 159 34576162 TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding. Tat (R52A) and Tat (R53A) were constructed by the PCR overlapping mutagenesis of the Tat gene. 2021 International journal of molecular sciences Method HIV R52A;R53A 5;20 9;24 Tat;Tat;Tat 0;15;85 3;18;88 34576162 TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding. The mutants and reporter-fused forms included Tat (R52A), Tat (R53A), Tat (R52A)-EGFP, and Tat (R53A)-EGFP. 2021 International journal of molecular sciences Method HIV R52A;R52A;R53A;R53A 51;75;63;96 55;79;67;100 Tat;Tat;Tat;Tat 46;58;70;91 49;61;73;94 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. For the construction of Gag-iCherry BAP-V4/Y712A, the NheI/BamHI fragment containing the mutation was cloned. 2021 Viruses Method HIV Y712A 43 48 Gag 24 27 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. HIV Env BAP-V4, BAP-V4-fluorescent variants (Gag-iGFP, Gag-iCherry, Gag-iCerulean) or endocytic mutants (BAP-V4-Y712A and BAP-V4-LL855A) were nucleofected into J-BirA cells or co-nucleofected with BirA plasmid into Jurkat cells. 2021 Viruses Method HIV Y712A 112 117 Env;Gag;Gag;Gag 4;45;55;68 7;48;58;71 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. The endocytic mutants BAP-V4-Y712A and BAP-V4-LL855A were generated by overlap extension PCR, and the fragment was inserted between NheI and BamHI and between BamHI and XhoI, respectively, and confirmed by sequencing. 2021 Viruses Method HIV Y712A 29 34 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. To study the VS transfer of the HIV Gag-iCherry BAP-V4/Y712A mutant, the wild type and tyrosine mutant were nucleofected into J-BirA cells, and the assay was performed as indicated above with some modifications. 2021 Viruses Method HIV Y712A 55 60 Gag 36 39 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. Inclusion criteria included diagnosis of HIV-1 infection >=3 months before screening, plasma HIV-1 RNA >=10,000 copies/mL, CD4+ T-cell count >200/mm3, no evidence of NNRTI-associated resistance mutations (eg, K103N, Y181C, and V108I) appearing in the Stanford University HIV Drug Resistance Database, and no evidence of active hepatitis C or hepatitis B infection. 2022 Journal of acquired immune deficiency syndromes (1999) Method HIV K103N;V108I;Y181C 209;227;216 214;232;221 NNRTI 166 171 HIV infections 41 56 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Each VSV-G pseudotyped lentiviral vector included VSVG-CGW-Myr (+) AnkGAG1D4-EGFP, VSVG-CGW-Myr (+) AnkGAG1D4-S45Y-EGFP, and VSVG-CGW-Myr (+) AnkA32D3-EGFP. 2021 Biomolecules Method HIV S45Y 110 114 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Generation of SupT1 Cells Stably Expressing Ankyrin Protein, AnkGAG1D4-EGFP, AnkGAG1D4-S45Y-EGFP, and AnkA32D3-EGFP by Lentiviral Gene Transferring Method. 2021 Biomolecules Method HIV S45Y 87 91 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. In order to compare the function of AnkGAG1D4 and AnkGAG1D4-S45Y in HIV-1 MIR virus production, HIV-1 NL4-3 MIRCAI201V was generated. 2021 Biomolecules Method HIV S45Y 60 64 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. A similar procedure was used for the G118R mutant residue in chain C. 2022 Antimicrobial agents and chemotherapy Method HIV G118R 37 42 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. A similar procedure was used for the R263K mutant residue in chain C. 2022 Antimicrobial agents and chemotherapy Method HIV R263K 37 42 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. A similar procedure was used for the R263K mutant residue of chain C. 2022 Antimicrobial agents and chemotherapy Method HIV R263K 37 42 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. For G118R residues in chains A and C, a localized Prime calculation was executed to optimize the interaction of G118R with both E92 and the 3' hydroxy of the tDNA terminal thymidine. 2022 Antimicrobial agents and chemotherapy Method HIV G118R;G118R 4;112 9;117 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The "Select Rotamer" function was then used to select a conformation of the G118R mutant residue that best interacted with the 3' hydroxy of the tDNA terminal thymidine (base 11) in chain G, while forming a hydrogen bonding network with E92 in chain A of the HIV-1 integrase catalytic core. 2022 Antimicrobial agents and chemotherapy Method HIV G118R 76 81 IN 265 274 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The "Select Rotamer" function was then used to select a conformation of the R263K mutant residue that best interacted with the 5' phosphate of the vDNA adenosine (base 18) in chain F while maintaining a conformation similar to the wild-type R263 amino acid side chain. 2022 Antimicrobial agents and chemotherapy Method HIV R263K 76 81 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The "Select Rotamer" function was used to select a conformation of the R263K mutant residue in chain A from the model in which R263K best interacted with both N144 and Q146 in chain A while maintaining a conformation similar to the wild-type R263 amino acid side chain. 2022 Antimicrobial agents and chemotherapy Method HIV R263K;R263K 71;127 76;132 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The protein/substrate complex with mutations of the R263 residue was constructed from the HIV-1 intasome structure (PDB ID 5U1C) in a manner similar to that for the G118R mutant protein. 2022 Antimicrobial agents and chemotherapy Method HIV G118R 165 170 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The resulting coordinates for both R263K homology models were captured in Maestro software, and the hydrogens were removed from both proteins and substrates. 2022 Antimicrobial agents and chemotherapy Method HIV R263K 35 40 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The resulting R263K homology model was then used as a starting geometry for the construction of a second R263K model containing an alternate conformation of this residue. 2022 Antimicrobial agents and chemotherapy Method HIV R263K;R263K 14;105 19;110 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Wild-type and R263K, G118R, or G118R/E138K mutant integrase-DNA-bead complexes were formed, and unbound protein was removed. 2022 Antimicrobial agents and chemotherapy Method HIV E138K;G118R;G118R;R263K 37;21;31;14 42;26;36;19 IN 50 59 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. A similar procedure was used for the L74M mutant residue in chain C. 2022 Antimicrobial agents and chemotherapy Method HIV L74M 37 41 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The "Select Rotamer" function was then used to select a conformation of the L74M mutant residue in chain A that best interacted with the surrounding residues while maintaining a conformation similar to the wild-type L74 amino acid side chain. 2022 Antimicrobial agents and chemotherapy Method HIV L74M 76 80 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The protein/substrate complex containing the triple mutant L74M V75A G118R was constructed using the procedure described above using our previously generated HIV-1 intasome G118R homology model as the initial HIV-1 intasome structural template. 2022 Antimicrobial agents and chemotherapy Method HIV G118R;G118R;L74M;V75A 69;173;59;64 74;178;63;68 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The protein/substrate complexes involving amino acid changes at L74 and V75 were constructed as previously described using either the HIV-1 intasome structure (Protein Data Bank [PDB] ID 5U1C) or our G118R HIV-1 intasome homology model. 2022 Antimicrobial agents and chemotherapy Method HIV G118R 200 205 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. QuickChange Lightning Multisite or QuickChange II XL (Agilent) site-directed mutagenesis kits were used to sequentially revert E138A and other NNRTI mutations to wild type. 2021 Journal of the International AIDS Society Method HIV E138A 127 132 NNRTI 143 148 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Single colonies containing E138A were isolated from bulk-cloned plasma-derived plasmid preparations. 2021 Journal of the International AIDS Society Method HIV E138A 27 32 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. MT-2 cells were infected at an MOI of 0.005 (low MOI) or 0.05 (high MOI) in 80 nM GSK'254 or GSK'795 with variants of RepRlucNL4-3GagP373S (WT V370A, V362I, or V370M). 2022 Antimicrobial agents and chemotherapy Method HIV V362I;V370A;V370M 150;143;160 155;148;165 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. NL4-3GagP373S (WT) and the SDM NL4-3 GagP373SV370A (V370A) were used to start the selections. 2022 Antimicrobial agents and chemotherapy Method HIV V370A 52 57 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. pNLRepRlucP373S (the P373S change is in the Gag gene and converts an outlier polymorphism in the NL4-3 gene to the prevalent amino acid in the population) plasmids containing SDMs in Gag or gag/pr regions from clinical isolates were transfected into HEK 293T cells, and the supernatant containing recombinant virus was harvested after 4 to 5 days. 2022 Antimicrobial agents and chemotherapy Method HIV P373S 21 26 Gag;Gag;Gag;PR 44;183;190;194 47;186;193;196 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. These variants were selected as parent virus based on common WT and V370A expression in HIV-1 subtypes (47% WT and ~36% V370A as indicated by the LANL HIV sequence database (https://www.hiv.lanl.gov/content/index). 2022 Antimicrobial agents and chemotherapy Method HIV V370A;V370A 68;120 73;125 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). Additional DRMs only detected by Sanger to NRTIs (L74I, D67N, K70E and K219R) and NNRTIs (V106M, K101E and P225H) were described using the Stanford HIV database. 2021 The Pan African medical journal Method HIV D67N;K101E;K219R;K70E;L74I;P225H;V106M 56;97;71;62;50;107;90 60;102;76;66;54;112;95 NNRTI;NRTI 82;43 88;48 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). The PANDAA assay differentiates the wild type allele 2 (labeled VIC) and the individual allele 1 (labeled FAM) coding for each DRM (K65R, K103NS, M184VI, Y181C, and G190A). 2021 The Pan African medical journal Method HIV G190A;K103N;K103S;K65R;M184I;M184V;Y181C 165;138;138;132;146;146;154 170;144;144;136;152;152;159 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). The results for each sample were classified by the detection of DRMs as either wild-type or mutant at codon K65R, Y181C, M184VI, K103NS and G190A. 2021 The Pan African medical journal Method HIV G190A;K103N;K103S;K65R;M184I;M184V;Y181C 140;129;129;108;121;121;114 145;135;135;112;127;127;119 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Due to abnormal sizes of M50I mutant (the diameters of the mutant particles were 190~300 nm, while those of Wt were 110~130 nm, and in this current study, the mutant previously used is renamed mNL(IN:M50I) as described in Section 3.1 below) with a defective autoprocessing of Gag and GagPol polyproteins (lacking of the cleaved mature forms of MA (p17), CA (p24), PR, RT, and IN in the virus particles), we could not find an appropriate internal control for WB. 2021 Viruses Method HIV M50I;M50I 25;200 29;204 p24;Gag;IN;IN;Matrix;Capsid;PR;RT 358;276;197;376;344;354;364;368 361;279;199;378;346;356;366;370 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. To predict IN:M50I and IN:V151I structure in IN and RH fusion protein, an assembled structure was also constructed using AIDA program. 2021 Viruses Method HIV M50I;V151I 14;26 18;31 IN;IN;IN 11;23;45 13;25;47 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We did not focus on minor variants for this study as our goal was to define the combination IN:M50I with a compensatory mutation. 2021 Viruses Method HIV M50I 95 99 IN 92 94 34871089 Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. Patients with previously documented HIV-2 infection, with active AIDS, and with documented genotypic evidence of >=1 NNRTI resistance-associated mutation (RAM) from a predefined list of the following NNRTI RAMs at screening were excluded: A98G, L100I, K101E, K101P, K101Q, K103H, K103N, K103S, K103T, V106A, V106M, V108I, E138A, E138G, E138K, E138Q, E138R, V179D, V179E, V179T, Y181C, Y181I, Y181V, Y188C, G190A, G190C, G190E, G190Q, G190S, G190T, P225H, F227C, Y188H, Y188L, M230I, M230L, P236L, K238N, K238T, and Y318F. 2022 Antimicrobial agents and chemotherapy Method HIV A98G;E138A;E138G;E138K;E138Q;E138R;F227C;G190A;G190C;G190E;G190Q;G190S;G190T;K101E;K101P;K101Q;K103H;K103N;K103S;K103T;K238N;K238T;L100I;M230I;M230L;P225H;P236L;V106A;V106M;V108I;V179D;V179E;V179T;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L;Y318F 239;322;329;336;343;350;455;406;413;420;427;434;441;252;259;266;273;280;287;294;497;504;245;476;483;448;490;301;308;315;357;364;371;378;385;392;399;462;469;515 243;327;334;341;348;355;460;411;418;425;432;439;446;257;264;271;278;285;292;299;502;509;250;481;488;453;495;306;313;320;362;369;376;383;390;397;404;467;474;520 NNRTI;NNRTI 117;200 122;205 AIDS;HIV infections 65;36 69;51 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. DNA fragments encoding PR/RT from the NL4-3 clone (HIV-1 subtype B) or the 92UG037 reference strain (HIV-1 subtype A1) with or without K101E, E138A, E138K, or E138T RT mutations were synthesized and ligated into replication-defective proviral vectors at Monogram Biosciences. 2022 Antimicrobial agents and chemotherapy Method HIV E138A;E138K;E138T;K101E 142;149;159;135 147;154;164;140 PR;RT;RT 23;26;165 25;28;167 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Full-length NL4-3 proviral vectors and chimeric ConA6 integrase gene-containing proviral vectors in the NL4-3 backbone, with or without L74I integrase mutations, were used to prepare virus stocks as previously described. 2022 Antimicrobial agents and chemotherapy Method HIV L74I 136 140 IN;IN 54;141 63;150 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Mutations (L74I, G140R, Q148R, and I74L) were introduced into the NL4-3 or ConA6 parental vectors by site-directed mutagenesis using the Q5 site-directed mutagenesis kit (New England Biolabs, Ipswich, MA). 2022 Antimicrobial agents and chemotherapy Method HIV G140R;I74L;L74I;Q148R 17;35;11;24 22;39;15;29 Matrix 201 203 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Variants with or without I74L integrase mutations were constructed using site-directed mutagenesis. 2022 Antimicrobial agents and chemotherapy Method HIV I74L 25 29 IN 30 39 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. We excluded individuals with prior evidence of NNRTI-associated resistance mutations based on the IAS-USA HIV drug-resistance mutations list (2019) (V90I, A98G, L100I, K101E/H/P/Q/R/N, K103N/S, V106A/M/I, V108I, E138K/A/G/Q/R, V179D/F/L/T, Y181C/I/V, Y188L/C/H, G190A/S/E,H221Y, P225H, F227L/C/R, M230L/I and L234I). 2022 Journal of the International AIDS Society Method HIV G190A;G190E;G190S;H221Y;A98G;E138A;E138G;E138K;E138Q;E138R;F227C;F227L;F227R;K101E;K101H;K101N;K101P;K101Q;K101R;K103N;K103S;L100I;L234I;M230I;M230L;P225H;V106A;V106I;V106M;V108I;V179D;V179F;V179L;V179T;V90I;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 262;262;262;272;155;212;212;212;212;212;286;286;286;168;168;168;168;168;168;185;185;161;309;297;297;279;194;194;194;205;227;227;227;227;149;240;240;240;251;251;251 271;271;271;277;159;225;225;225;225;225;295;295;295;183;183;183;183;183;183;192;192;166;314;304;304;284;203;203;203;210;238;238;238;238;153;249;249;249;260;260;260 NNRTI 47 52 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Proviral plasmids pNL4-3 V260I, R263K, and R263R were generated by an overlapping-PCR technique (PCR1 with primers a + b, PCR2 with primers c + d, PCR 3 with PCR 1 and 2 as a template using primer a + d) using their respective primer pairs (Table 1). 2021 International journal of molecular sciences Method HIV R263K;R263R 32;43 37;48 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. The respective wildtype and mutated fragments of HIV-1 exon 2/2b were added at their authentic position between SD2 or SD2b, by using primer pairs #5941/#6040 (V260I), #5941/#6042 (V260V silent), #5941/#6041 (R263K) and #5941/#6043 (R263R silent). 2021 International journal of molecular sciences Method HIV R263K;R263R;V260I;V260V 209;233;160;181 214;239;165;187 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. T18A TCR were bacterially expressed and refolded as previously described. 2022 Frontiers in immunology Method HIV T18A 0 4 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The HIV Gag p24 TL9 peptide (TPQDLNTML180-188), the escape variant Q182S, Q182T, T186S, and Q182S/T186S TL9 peptide were synthesized at > 95% purity, were synthesized at GL Biochem corporation and confirmed by high-performance liquid chromatography. 2022 Frontiers in immunology Method HIV Q182S;Q182S;Q182T;T186S;T186S 67;92;74;81;98 72;97;79;86;103 p24;Gag 12;8 15;11 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The T18A in complexes with HLA B*81:01 and Gag TL9 peptide was crystallized in the presence of 0.2 M Potassium chloride, 0.05 M HEPES, 35% v/v Pentaerythritol propoxylate (5/4 PO/OH), pH 7.5. 2022 Frontiers in immunology Method HIV T18A 4 8 Gag 43 46 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The T18A TCR was fixed on the streptavidin-coated flow-cell surface of a SA sensor chip and the pMHC complexes were used as analyte. 2022 Frontiers in immunology Method HIV T18A 4 8 35207677 Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort. Furthermore, we excluded people with the following mutations for NNRTI: L100I, K101E/H/NP/Q, E138A/G/K/Q/R, V179L, Y181C/F/G/I/S/V, Y188L, G190A/C/E/Q/S/T/V, H221Y, F227C/L, and M230L. 2022 Journal of personalized medicine Method HIV E138A;E138G;E138K;E138Q;E138R;F227C;F227L;G190A;G190C;G190E;G190Q;G190S;G190T;G190V;H221Y;K101E;K101H;K101N;K101P;K101Q;L100I;M230L;V179L;Y181C;Y181F;Y181G;Y181I;Y181S;Y181V;Y188L 93;93;93;93;93;165;165;139;139;139;139;139;139;139;158;79;79;79;79;79;72;178;108;115;115;115;115;115;115;132 106;106;106;106;106;172;172;156;156;156;156;156;156;156;163;91;91;91;91;91;77;183;113;130;130;130;130;130;130;137 NNRTI 65 70 35207677 Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort. Therefore, we considered eligible for treatment with long-acting CAB/RPV, PWH with an undetectable HIV-RNA (<50 copies/mL) for at least 12 months, who are HBsAg negative, and who do not have evidence of NNRTI (except K103N) or Integrase Strand Transfer Inhibitor (INSTI) mutations. 2022 Journal of personalized medicine Method HIV K103N 217 222 IN;INSTI;NNRTI 227;264;203 236;269;208 35207677 Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort. We also excluded PWH with the following INSTI mutations: T66I, E92Q, G118R, G140S, Y143A/C/G/H/K/R/S, S147G, Q148H/K/N/R, N155H/S/T, and R263K. 2022 Journal of personalized medicine Method HIV E92Q;G118R;G140S;N155H;N155S;N155T;Q148H;Q148K;Q148N;Q148R;R263K;S147G;T66I;Y143A;Y143C;Y143G;Y143H;Y143K;Y143R;Y143S 63;69;76;122;122;122;109;109;109;109;137;102;57;83;83;83;83;83;83;83 67;74;81;131;131;131;120;120;120;120;142;107;61;100;100;100;100;100;100;100 INSTI 40 45 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. The following primer sets were used to introduce mutations: P37S forward, 5'-GGC AGA GGT AGT GTC AGG ATT TCA AGC G-3'; reverse, 5'-CGC TTG AAA TCC TGA CAC TAC CTC TGC C-3'; R98S forward, 5'-GCA. 2022 Microbiology spectrum Method HIV P37S;R98S 60;173 64;177 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. To construct SIVsmm804E-CL757-S37-S98 (CL757-SS) full-length clone, amino acid substitutions "P37S" and "R98S" were introduced into CL757-WT capsid using a QuikChange II Site-Directed Mutagenesis kit (Agilent) according to the manufacturer's instructions. 2022 Microbiology spectrum Method HIV P37S;R98S 94;105 98;109 Capsid 141 147 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. The Q7K mutation was introduced to prevent autoproteolysis; the resulting construct is referred to as 'WT HIV-1 PR' throughout the manuscript. 2021 Virus evolution Method HIV Q7K 4 7 PR 112 114 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Binding of K258R IN to selected protein binding partners was confirmed by co-immunoprecipitation monitored by Western blot. 2022 Nature communications Method HIV K258R 11 16 IN 17 19 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Either WT HIV-1 IN or IN harboring the K258R mutation was cloned into a mammalian expression vector (pJET). 2022 Nature communications Method HIV K258R 39 44 IN;IN 16;22 18;24 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Enriched peptides immunoprecipitated by WT and K258R mutant IN were further subjected to gene ontology analysis performed with gProfiler software. 2022 Nature communications Method HIV K258R 47 52 IN 60 62 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. HeLa cells were grown on 12 mm circle coverslips (Electron Microscopy Sciences) for 24 h, exposed to mock supernatants or those containing WT or K258R IN mutant HIV-1 at an MOI of 10 for 16 h, fixed with 4% PFA for 10 min at room temperature (RT), and permeabilized with 0.5% Triton X-100 for 10 min. 2022 Nature communications Method HIV K258R 145 150 IN;RT 151;243 153;245 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Based on autologous viral sequences, we designed peptides for Gag-DA9 (298DRFYKTLRA306), Env-EL9 (584ERYLKDQQL592) and for the observed Env-EL9 variants at positions L592R (ERYLKDQQR) and K588R + L592R (ERYLRDQQR). 2022 Retrovirology Method HIV K588R;L592R;L592R 188;166;196 193;171;201 Env;Env;Gag 89;136;62 92;139;65 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. To study the role of the mutations in Env-EL9 epitope, R592L and K588R were introduced into an Env-expression plasmid containing the L592R mutation to generate WT pseudovirus (584ERYLKDQQL592), and escape + compensatory (ESC + COM) (K588R + L592R). 2022 Retrovirology Method HIV K588R;K588R;L592R;L592R;R592L 65;233;133;241;55 70;239;138;246;60 Env;Env 38;95 41;98 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. We evaluated the Gp160 stability for the WT amino acidic sequence, the sequence with the escape mutation L592R (ESC variant) and, the sequence with both the escape L592R and compensatory K588R mutations (ESC + COM variant). 2022 Retrovirology Method HIV K588R;L592R;L592R 187;105;164 192;110;169 gp160 17 22 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. To introduce the M46I mutation, the mutagenesis module of PyMol software was utilized. 2022 Viruses Method HIV M46I 17 21 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. 52 wk after acquiring infection, 96% of his viral sequences carried the R264K sequence (1/25 had R264I) and all had M268. 2001 The Journal of experimental medicine Result HIV R264I;R264K 97;72 102;77 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Approximately 20 mo after presentation the R264G mutation was found in all sequences. 2001 The Journal of experimental medicine Result HIV R264G 43 48 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. As described previously 7, the hemophiliac patients 007 and 025 had w/t epitope sequences with R264 and L268; however, L268M occurred relatively early in the course of infection (online supplemental Table SI). 2001 The Journal of experimental medicine Result HIV L268M 119 124 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Both have HLA-B2705, but did not select R264K during the study period. 2001 The Journal of experimental medicine Result HIV R264K 40 45 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. However, it is also apparent from the phylogenetic tree that at least one K264R reversion mutation has occurred. 2001 The Journal of experimental medicine Result HIV K264R 74 79 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. If, for example, the fixation of R264G in patient RT occurred between 0.9 and 2.4 yr after enrolment, as is compatible with the phylogenetic analysis, then this fixation event took no more than ~18 mo. 2001 The Journal of experimental medicine Result HIV R264G 33 38 RT 50 52 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In each patient when the R264K mutant was first detected, a majority of the preceding viruses sampled had M268. 2001 The Journal of experimental medicine Result HIV R264K 25 30 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In the first sample available for sequencing, collected 12 wk after initial presentation, all proviral sequences showed the R264K mutation and M268. 2001 The Journal of experimental medicine Result HIV R264K 124 129 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In the sequences where this occurred, but not in the escape sequences, there was an increasing frequency of the other reversion mutation M268L (online supplemental Table SI, and. 2001 The Journal of experimental medicine Result HIV M268L 137 142 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In this patient, the R264K mutation may have arisen four times, but never reaches fixation (i.e., 100% frequency), perhaps because antiviral therapy was given after that time which altered the selection pressure on viral evolution. 2001 The Journal of experimental medicine Result HIV R264K 21 26 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In this subject, K264 occurred in association with T280S and R286K in all sequences. 2001 The Journal of experimental medicine Result HIV R286K;T280S 61;51 66;56 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Patient 025 also had detectable HLA-B27 gag-specific CTLs before the appearance of the R264K mutation. 2001 The Journal of experimental medicine Result HIV R264K 87 92 Gag 40 43 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Selection of R264K and R264G Mutants. 2001 The Journal of experimental medicine Result HIV R264G;R264K 23;13 28;18 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Similarly, the R264G mutation appears only in the context of the amino acid residues L268 and E260D. 2001 The Journal of experimental medicine Result HIV E260D;R264G 94;15 99;20 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Subsequently, each developed the R264K mutation as disease progressed with increasing viral loads and falling CD4+ counts (7; online supplemental Table SI, and. 2001 The Journal of experimental medicine Result HIV R264K 33 38 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Such observations suggest that although L268 and R264 are intimately related, they are not in direct linkage; the rise of M268L is not simply due to it being linked to a selectively favored K264R virus. 2001 The Journal of experimental medicine Result HIV K264R;M268L 190;122 195;127 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. The phylogenetic analysis also supports the selection of R264K in patients 007 and 777. 2001 The Journal of experimental medicine Result HIV R264K 57 62 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. These data, along with a review of the Los Alamos database (Table ), indicate that R264K mutation occurs rarely in subtype B viruses. 2001 The Journal of experimental medicine Result HIV R264K 83 88 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. These mutations at codons 280 and 286 are not seen in any of the four HLA-B27-positive patients with R264K and L268M, but are commonly seen in subtype A viruses 20. 2001 The Journal of experimental medicine Result HIV L268M;R264K 111;101 116;106 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. This mutation was always associated with L268, and a E260D mutation in the NH2-terminal flanking region of the epitope, at this and at all subsequent time points. 2001 The Journal of experimental medicine Result HIV E260D 53 58 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. This was confirmed by tetramer staining but responses became undetectable as measured by tetrameric complexes, bulk culture, and peptide generated cell lines 1 yr after the rise to fixation of the R264K mutation. 2001 The Journal of experimental medicine Result HIV R264K 197 202 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Two amino acid changes have occurred on this branch: E260D and R264G. 2001 The Journal of experimental medicine Result HIV E260D;R264G 53;63 58;68 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. When effective antiretroviral therapy was started 16 wk after presentation, the viral load fell and the R264K mutation persisted. 2001 The Journal of experimental medicine Result HIV R264K 104 109 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. When the viral load was high and the CTL response was undetectable, the epitope sequences partially reverted from K264 to w/t (K264R). 2001 The Journal of experimental medicine Result HIV K264R 127 132 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. As expected, the presence of mutations associated with resistance to non nucleoside reverse transcriptase inhibitors (NNRTIs), only revealed by sequencing analysis showed VI 081 (associated with a reduced drug sensitivity to efavirenz plus nevirapine), V118I (associated with moderate phenotypic lamivudine resistance) and the presence of K103N (key mutation for all the NNRIs) plus Y181C (with variable effects on susceptibility to efavirenz, besides resistance to nevirapine). 2001 BMC microbiology Result HIV K103N;V118I;Y181C 339;253;383 344;258;388 NRTI;NNRTI 73;118 105;124 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. In our experimental conditions, K70R mutation (a mixed pattern showing the presence of WT and MU), the first mutation to appear in zidovudine treated patients, was revealed only by LIPA. 2001 BMC microbiology Result HIV K70R 32 36 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. In particular, the most frequent substitutions, by genotyping analysis, are present at codon 36 [M36I alone (7 cases) or associated with L10V (2 cases)], at codon 63 [L63P alone (5 cases) or associated with V77I (2 cases)] and at codon 77 [V77I (5 cases)], while L10V was always found in association with A71V or M36I. 2001 BMC microbiology Result HIV A71V;L10V;L10V;L63P;M36I;M36I;V77I;V77I 305;137;263;167;97;313;207;240 309;141;267;171;101;317;211;244 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. LIPA showed V82A mutation (a mixed pattern showing the presence of WT and MU) correlated with resistance to indinavir and ritonavir, (Table 1) and "indeterminate" results (I50/I54, and L90) were observed in three and two cases respectively. 2001 BMC microbiology Result HIV V82A 12 16 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. Moreover, nine viral samples gave indeterminate results by LIPA, showing codons lacking different amino acid positions (association of M41L + T69K70 + L74V75: 1 case, F214T215: 1 case, M184V: 1 case, T69K70: 2 cases and L74V75: 4 cases). 2001 BMC microbiology Result HIV M184V;M41L 185;135 190;139 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. As shown in Table 1, E630Q, S641G, and N651I mutations were found distinctively in the CHR region of MT-4/17-3-6, but all of these residues were placed on the outer side, which had no direct interaction with the inner NHR coils. 2005 Biochemical and biophysical research communications Result HIV E630Q;N651I;S641G 21;39;28 26;44;33 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. However, by the focusing on the L565M mutation in the inner and central moiety, which would be not affected by the other regions, we found that this mutation might be an important factor for the resistance of MT-4/17-3-6 to peptide inhibitors with respect to coiled-coil formation and cell fusion. 2005 Biochemical and biophysical research communications Result HIV L565M 32 37 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. Just beside H564, the L565M mutation was found in MT-4/17-3-6 compared with MT-4/LAI. 2005 Biochemical and biophysical research communications Result HIV L565M 22 27 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. S641G and N651I were adjacent to Y638 and Q650. 2005 Biochemical and biophysical research communications Result HIV N651I;S641G 10;0 15;5 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. Therefore, it was thought that the L565M mutation would be a major factor affecting the coiled-coil stabilization by these bridges, and the binding of peptide fusion inhibitors might be distinctively disturbed by this stabilization in MT-4/17-3-6. 2005 Biochemical and biophysical research communications Result HIV L565M 35 40 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. These large intra-subtype differences can be explained by our model, which showed that the L565M mutation could stabilize the coiled-coil without affecting the structure of the protein widely. 2005 Biochemical and biophysical research communications Result HIV L565M 91 96 16054592 L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. We tentatively optimized another virtual model with mutation of only L565M from MT-4/LAI, and also found similar Y638-H564 hydrogen bonds as in the MT-4/17-3-6 model (data not shown). 2005 Biochemical and biophysical research communications Result HIV L565M 69 74 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Each of the single mutants, N255D and N265D, and the double mutant RTs were tested for their sensitivity to a selected set of NRTIs (AZTTP, ddATP, ddCTP, d4TTP and 3TCTP) or the NNRTIs (nevirapine and delavirdine). 2005 AIDS research and therapy Result HIV N255D;N265D 28;38 33;43 NNRTI;NRTI;RT 178;126;67 184;131;70 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. However, in vitro biochemical experiments do show some resistance to AZTTP and it has been suggested this is due to K65R decreasing the rate of AZTMP excision. 2005 AIDS research and therapy Result HIV K65R 116 120 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. However, with respect to the DNA aptamer RT10 and the single RNA aptamer tested (Rknot1.1), the N255D mutant was similar to wild type, while both N265D and Dbl mutants were significantly resistant. 2005 AIDS research and therapy Result HIV N255D;N265D 96;146 101;151 RT 41 43 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. In contrast, both N255D and Dbl mutant RTs were hypersensitive (10-fold) to DNA aptamer RT8, while the N265D mutant displayed wild type levels of sensitivity (Table 1). 2005 AIDS research and therapy Result HIV N255D;N265D 18;103 23;108 RT;RT 39;88 42;90 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. In contrast, mutations shown to confer resistance to multiple NRTIs, including E89G, K65R and M184V displayed low levels of resistance to RT1t49 (2-5 fold), with K65R displaying the highest level of resistance (5-fold). 2005 AIDS research and therapy Result HIV E89G;K65R;K65R;M184V 79;85;162;94 83;89;166;99 NRTI 62 67 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. In each of these cases, the N265D mutation conferred a greater degree of resistance compared to the N255D mutation. 2005 AIDS research and therapy Result HIV N255D;N265D 100;28 105;33 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. K65R is known to cause resistance to all clinically approved NRTIs except AZT in patients. 2005 AIDS research and therapy Result HIV K65R 0 4 NRTI 61 66 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. The similarity between resistance profiles of N255D and N265D mutant RTs to both DNA aptamers (RT1t49, RT26, RT4, RT6) suggest that the residues N255 and N265 are important contacts for several classes of DNA aptamers. 2005 AIDS research and therapy Result HIV N255D;N265D 46;56 51;61 RT;RT;RT;RT 69;103;109;114 72;105;111;116 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. These results indicate that although the N255D and Dbl mutant RTs possess residual polymerase-dependent RNase H activity under single cycle cleavage conditions, the specificity of cleavage under such conditions has not been retained. 2005 AIDS research and therapy Result HIV N255D 41 46 Pol;RT 83;62 93;65 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Together, these results indicate that both aptamer resistance mutations N255D and N265D result in a severe reduction of HIV-1 RT mediated RNase H cleavage under challenged conditions. 2005 AIDS research and therapy Result HIV N255D;N265D 72;82 77;87 RT 126 128 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Unlike the previous challenged RNase H reactions (Figure 1), N255D, N265D, and Dbl mutant RTs were able to make comparable amounts of polymerase-dependent RNase H cleavage products (Figure 2). 2005 AIDS research and therapy Result HIV N255D;N265D 61;68 66;73 Pol;RT 134;90 144;93 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Variants of HIV-1 RT shown to confer resistance to AZT (T215Y/M41L) and ddI and ddC (L74V) were sensitive to inhibition by RT1t49 (Table 3). 2005 AIDS research and therapy Result HIV L74V;M41L;T215Y 85;62;56 89;66;61 RT 18 20 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. We investigated whether the aptamer-resistance mutations, N255D and N265D, would affect the sensitivity of HIV-1 RT to other DNA and RNA aptamers directed to HIV-1 RT. 2005 AIDS research and therapy Result HIV N255D;N265D 58;68 63;73 RT;RT 113;164 115;166 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. While there appeared to be a limited cleavage by both N255D and Dbl mutants, products formed were altered in size compared to wild type products (Figure 1A, lane 1 vs. 2005 AIDS research and therapy Result HIV N255D 54 59 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Based on these results, we reasoned that these IN C-terminal mutants blocked infection mostly by affecting earlier steps of HIV-1 life cycle, such as reverse transcription and/or viral DNA nuclear import steps, which are different from the action of D64E mutant on viral DNA integration. 2005 Retrovirology Result HIV D64E 250 254 RT;IN 150;47 171;49 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. In agreement with the finding by MAGI assay described in figure 3, the Luc activity detected in KK215,9AA, KK240,4AE and RK263,4AA mutant samples were approximately 13%, 5% and 36% of level of D64E mutant infection. 2005 Retrovirology Result HIV D64E 193 197 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. In order to specifically investigate the effect of IN mutants on early steps during HIV-1 infection prior to integration, an IN class I mutant D64E was also included as control. 2005 Retrovirology Result HIV D64E 143 147 IN;IN 51;125 53;127 HIV infections 84 99 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. In the wt, D64E and RK263,4AA virus-infected samples, there were respectively 70%, 72% and 68% of viral DNA associated with nuclear fractions. 2005 Retrovirology Result HIV D64E 11 15 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Interestingly, results showed that the IN mutant D64E virus infection induced the highest level of beta-Gal positive cells, whereas infection with viruses containing IN mutants KK215,9AA, KK240,4AE or RK263,4AA yielded much lower levels of beta-Gal positive cells, which only reached approximately 11%, 5% or 26% of the level of D64E virus infection. 2005 Retrovirology Result HIV D64E;D64E 49;329 53;333 IN;IN 39;166 41;168 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. It indicates that, even though the IN mutant D64E virus is defective for integrating viral DNA into host genome, tat expression from nucleus-associated and unintegrated viral DNAs can activate HIV-1 LTR-driven beta-Gal expression in HeLa-CD4-CCR5-LTR-beta-Gal cells. 2005 Retrovirology Result HIV D64E 45 49 LTR;LTR;Tat;IN 199;247;113;35 202;250;116;37 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Results showed that the D64E mutant infection in dividing C8166 T cells induced 14.3 x 104 RLU of luc activity. 2005 Retrovirology Result HIV D64E 24 28 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Results showed that the number of infected cells (beta-Gal positive cells) for D64E mutant reached approximately 14% of the wild type level (data not shown). 2005 Retrovirology Result HIV D64E 79 83 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. the Luc activity detected in cells infected by HIV-1 envelope competent KK215,9AA, KK240,4AE and RK263,4AA mutant viruses were approximately 13.5%, 6% and 29% of level of D64E mutant infection. 2005 Retrovirology Result HIV D64E 171 175 Env 53 61 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. there was no viral DNA integration detected in D64E mutant (lanes 3 to 4) and in all three C-terminal mutant infection samples (lanes 5 to 10), although similar levels of cellular beta-globin gene were detected in each sample. 2005 Retrovirology Result HIV D64E 47 51 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. This level of luc activity detected in D64E mutant infection is mostly due to nef gene expression from the unintegrated DNA. 2005 Retrovirology Result HIV D64E 39 43 Nef 78 81 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. To test the infectivity of different IN mutant viruses in HeLa-CD4-CCR5-LTR-beta-Gal cells, we first compared the infectivity of VSV-G pseudotyped wild type virus and the D64E mutant virus. 2005 Retrovirology Result HIV D64E 171 175 LTR;IN 72;37 75;39 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. A nested PCR approach allowed us to obtain products even from F61Y virus infected cells (where real-time PCR did not detect any products), but we were unable to recover any sequences for F61A mutant. 2006 Nucleic acids research Result HIV F61A;F61Y 187;62 191;66 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Among the four F61 mutants, F61L displayed some replication capability although it was at least 14 times less than the wild type (Figure 2B) at peak level. 2006 Nucleic acids research Result HIV F61L 28 32 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Among the mutants, F61L virus produced sequences with a distribution similar to wild type, with close to 50% consensus sequences. 2006 Nucleic acids research Result HIV F61L 19 23 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Amplified DNA was cloned and ~25 clones each for wild-type, F61L, F61W and F61Y mutant viruses were sequenced. 2006 Nucleic acids research Result HIV F61L;F61W;F61Y 60;66;75 64;70;79 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. At 2 h post infection, F61W was able to synthesize late RT products as efficiently as F61L. 2006 Nucleic acids research Result HIV F61L;F61W 86;23 90;27 RT 56 58 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. At 24 h post-infection, the copy number of 2-LTR circle DNA synthesized by wild type was 95, which is ~5 times higher than F61L and ~16 times more than that of F61W. 2006 Nucleic acids research Result HIV F61L;F61W 123;160 127;164 LTR 45 48 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. At 48 h post infection, wild-type virus was able to form 2-LTR circle DNA ~10 and ~27 times higher than F61L and F61W, respectively. 2006 Nucleic acids research Result HIV F61L;F61W 104;113 108;117 LTR 59 62 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. At day 8, the average p24 value of wild type was 1040 ng/ml and F61L and F61W produced only 72 and 10 ng/ml of p24 (Figure 2B and inset within this figure). 2006 Nucleic acids research Result HIV F61L;F61W 64;73 68;77 p24;p24 22;111 25;114 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Both F61A and F61Y failed to produce any detectable amounts of p24 protein. 2006 Nucleic acids research Result HIV F61A;F61Y 5;14 9;18 p24 63 66 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. F61A virus was non-infectious, while the infectivity of F61L, F61W and F61Y were 8.5, 2.5 and 0.6% that of wild type (Figure 2A). 2006 Nucleic acids research Result HIV F61L;F61W;F61Y;F61A 56;62;71;0 60;66;75;4 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. F61W was also replication defective with very low amount of p24 production through 20 days. 2006 Nucleic acids research Result HIV F61W 0 4 p24 60 63 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. For F61W mutant virus, 40% of the sequences had either large or partial deletions (Figure 4). 2006 Nucleic acids research Result HIV F61W 4 8 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. However, for mutants F61L and F61W, just as in the case of -ssDNA and gag DNA intermediates, the level of 2-LTR circle DNA was lower than wild type at 24 and 48 h post-infection, while F61A and F61Y mutants failed to make any 2-LTR circle DNA (Figure 3). 2006 Nucleic acids research Result HIV F61A;F61L;F61W;F61Y 185;21;30;194 189;25;34;198 LTR;LTR;Gag 108;228;70 111;231;73 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In order to evaluate the influence of F61 substitutions (F61L, F61W, F61Y and F61A) on HIV replication, molecular clones bearing these mutations were constructed to generate virus particles. 2006 Nucleic acids research Result HIV F61A;F61L;F61W;F61Y 78;57;63;69 82;61;67;73 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Interestingly, F61A mutant also displayed enhanced cleavage at +6 position of the U3. 2006 Nucleic acids research Result HIV F61A 15 19 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Mutants F61L, F61W and F61Y all show significant cleavage at this position, but are reduced 5- to 10-fold compared with wild-type levels. 2006 Nucleic acids research Result HIV F61L;F61W;F61Y 8;14;23 12;18;27 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. No p24 protein was detected in the culture supernatants of F61A and F61Y viruses. 2006 Nucleic acids research Result HIV F61A;F61Y 59;68 63;72 p24 3 6 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Of these three RT mutants, F61Y indeed shows the lowest level of cleavage, while F61A appears to be severely compromised (Figure 5D and Table 1). 2006 Nucleic acids research Result HIV F61A;F61Y 81;27 85;31 RT 15 17 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Similar to the -ssDNA, the amount of gag DNA synthesis increased from 2 to 24 h for wild-type, F61L, F61W and F61Y (Figure 3) whereas F61A failed to synthesize significant amount late RT products even at 24 h. 2006 Nucleic acids research Result HIV F61A;F61L;F61W;F61Y 134;95;101;110 138;99;105;114 Gag;RT 37;184 40;186 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The amount of 2-LTR circle DNA formed by wild type, F61L and F61W increased from 24 to 48 h (Figure 3), though the level of increase was much higher for wild type. 2006 Nucleic acids research Result HIV F61L;F61W 52;61 56;65 LTR 16 19 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The efficiency of -ssDNA DNA synthesis was in the order of wild-type>F61L>F61W>F61Y>F61A. 2006 Nucleic acids research Result HIV F61A;F61L;F61W;F61Y 84;69;74;79 88;73;78;83 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The F61A RT mutant was most compromised with 6% cleavage efficiency compared to wild-type HIV-1 RT. 2006 Nucleic acids research Result HIV F61A 4 8 RT;RT 9;96 11;98 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The presence of only one species of sequences with unprocessed PPT suggests that the F61Y RT may be defective in its ability to remove the PPT primer RNA (also see Discussion). 2006 Nucleic acids research Result HIV F61Y 85 89 RT 90 92 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The results show that mutants F61L, F61W and F61Y display mild reductions in cleavage at position -1 (Figure 5A and B and Table 1) with efficiencies of cleavage being 77, 68 and 50% of wild type (at 3 min). 2006 Nucleic acids research Result HIV F61L;F61W;F61Y 30;36;45 34;40;49 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The slow replication of F61W mutant is in partial agreement with a previous study, in which the F61W mutant virus displayed delayed replication kinetics. 2006 Nucleic acids research Result HIV F61W;F61W 24;96 28;100 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Virological analysis described above suggested a possible defect in the ability of F61Y RT-associated RNase H to efficiently remove the PPT primer from plus strand DNA. 2006 Nucleic acids research Result HIV F61Y 83 87 RT 88 90 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. We PCR amplified a 188 bp fragment around the U5-U3 junction from cells infected with wild-type, F61L, F61W and F61Y mutant viruses. 2006 Nucleic acids research Result HIV F61L;F61W;F61Y 97;103;112 101;107;116 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Although all of the substituted IN proteins displayed similar -2 processing activity and mAb33 binding affinity (data not shown), we elected to utilize the 3CS/F185H/W131D/F139D-encoding construct for further mutagenesis studies because this protein exhibited the highest solubility. 2006 Retrovirology Result HIV F139D;F185H;W131D 172;160;166 177;165;171 IN 32 34 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Furthermore, unlike sIN and the other derivatives, I267A and I267A/I268A have very similar Kd values for model viral and host DNA. 2006 Retrovirology Result HIV I267A;I267A;I268A 51;61;67 56;66;72 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Interestingly, the greatest reductions were seen with Ala substitution of the hydrophobic residues, Y226A, I267A, and I268A. 2006 Retrovirology Result HIV I267A;I268A;Y226A 107;118;100 112;123;105 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Only the R224A and K244A derivatives retained significant joining activity compared to the sIN, indicating that the epitope residues are important for protein function. 2006 Retrovirology Result HIV K244A;R224A 19;9 24;14 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Proteins with substitutions in the non-epitope residues W243A and R262A were more defective. 2006 Retrovirology Result HIV R262A;W243A 66;56 71;61 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The additional I268A substitution did not appear to alter the binding affinity of I267A. 2006 Retrovirology Result HIV I267A;I268A 82;15 87;20 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The best yield of purified soluble protein was obtained with the 3CS/F185H/W131D/F139D derivative: approximately 40 mg per liter of culture, after cleavage of the 6XHis tag and the final purification step of Heparin column chromatography. 2006 Retrovirology Result HIV F139D;F185H;W131D 81;69;75 86;74;80 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The data in Figure 3 show that the processing products obtained with the I267A derivative were strikingly different from the parental sIN. 2006 Retrovirology Result HIV I267A 73 78 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The dissociation kinetics of the I267A and I267A/I268A derivatives with all three model DNA substrates were altered compared to sIN; the fast dissociation was absent and only the slow dissociation kinetics were observed (data not shown). 2006 Retrovirology Result HIV I267A;I267A;I268A 33;43;49 38;48;54 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The I267A/I268A derivative is also less specific, but its nuclease activity appeared to diminish with distance from the 3'-end. 2006 Retrovirology Result HIV I267A;I268A 4;10 9;15 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The K244A derivative was largely unaffected in mAb33 binding, consistent with the variable results observed in our previous NMR studies. 2006 Retrovirology Result HIV K244A 4 9 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The Kd values for proteins containing F223A, R224A, Y226A, or K244A substitutions are comparable to that of the parental sIN with respect to all the model DNA substrates. 2006 Retrovirology Result HIV F223A;K244A;R224A;Y226A 38;62;45;52 43;67;50;57 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The most significant change was observed with the I267A and I267A/I268A substituted proteins, which showed more than a 2-fold increase in binding affinity compared with sIN. 2006 Retrovirology Result HIV I267A;I267A;I268A 50;60;66 55;65;71 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The mutations that were introduced for this purpose encoded proteins with the following additional substitutions: 3CS/F185H, 3CS/F185K, 3CS/F185H/W131D/F139D, and 3CS/F185K/W131D/F139D. 2006 Retrovirology Result HIV F139D;F139D;F185H;F185K;W131D;W131D;F185H;F185K 152;179;140;167;146;173;118;129 157;184;145;172;151;178;123;134 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The non-epitope substitution R262A derivative binds mAb33 as well as the parental protein sIN, as expected from previous NMR studies, while W243A, which may be involved in dimer interactions, is compromised for antibody binding. 2006 Retrovirology Result HIV R262A;W243A 29;140 34;145 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The R224A, and F223A sIN proteins were less seriously compromised for mAb33 binding. 2006 Retrovirology Result HIV F223A;R224A 15;4 20;9 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. W243 is believed to play a role in a CTD dimer interaction that may be compromised in the W243A derivative. 2006 Retrovirology Result HIV W243A 90 95 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. We therefore chose to analyze these residues in greater detail by generating both of the single substitutions, I267A and I268A, as well as the doubly substituted sIN protein, I267A/I268A. 2006 Retrovirology Result HIV I267A;I267A;I268A;I268A 111;175;121;181 116;180;126;186 16956392 HIV-2 Protease resistance defined in yeast cells. Among the 9 mutations observed in the MRT-8 Protease (4 conservative and 5 non-conservative), we focused on the 90th residue since the L90M substitution has already been classified as a major mutation in HIV-1 which confers resistance to SQV and LPV, and has been suggested to be associated with resistance to a yet undefined PI in HIV-2 Protease. 2006 Retrovirology Result HIV L90M 135 139 PR;PR;PI 44;338;326 52;346;328 16956392 HIV-2 Protease resistance defined in yeast cells. At the same time we created and tested the ROD L99F mutant, since this mutation was proposed to confer PI resistance in a study that scored the emergence of mutations in infected individuals failing an anti-protease containing regime, and no functional data of this suggested resistance is available. 2006 Retrovirology Result HIV L99F 47 51 PR;PI 207;103 215;105 16956392 HIV-2 Protease resistance defined in yeast cells. Conversely, the Phe residue in position 99 did not modify the respondent character of the Protease to either of the tested PIs (IC50HIV-2ROD L99F/IC50HIV-2RODwt = 0.67 for LPV and 0.98 for SQV). 2006 Retrovirology Result HIV L99F 141 145 PR;PI 90;123 98;126 16956392 HIV-2 Protease resistance defined in yeast cells. The galactose induced cell death was found to be directly linked to the protease enzyme activity, since when the Asp residue of the active site of the viral enzyme was modified to Ala (D25A mutant), the inactive Protease expressed in transformed cells (Fig 1C, lane 3) did not induce cell death when grown on galactose (Fig 1B). 2006 Retrovirology Result HIV D25A 185 190 PR;PR;Asp 72;212;113 80;220;116 16956392 HIV-2 Protease resistance defined in yeast cells. The HIV-2ROD Protease was mutated and the resultant ROD L90M mutant was tested for its susceptibility to LPV and SQV in yeast as was performed for HIV-2 Proteases from infected individuals. 2006 Retrovirology Result HIV L90M 56 60 PR;PR 13;153 21;162 16956392 HIV-2 Protease resistance defined in yeast cells. The results obtained, presented in Table 4, show that the L90M mutant have lost sensitivity to SQV but not to LPV (IC50HIV-2ROD L90M/IC50HIV-2RODwt = 3.7 and 0.75 respectively). 2006 Retrovirology Result HIV L90M;L90M 58;128 62;132 16956392 HIV-2 Protease resistance defined in yeast cells. When this HIV-2ROD Protease harbours amino acid substitutions known to be involved in HIV-2 PI resistance such as K45R, I54M, or M76V, cell growth, in spite of the presence of the inhibitors, was strongly arrested achieving in some cases only 4% of normal growth (Table 1) demonstrating a tight correlation between resistance, defined in physiological conditions, and loss of susceptibility, defined in our experimental system. 2006 Retrovirology Result HIV I54M;K45R;M76V 120;114;129 124;118;133 PR;PI 19;92 27;94 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. 9 had undetectable HIV RNA levels (less than 40 copies/ml) by the Roche Amplicor assay (Roche Diagnostics) within the last 6 months and had no evidence of K103N on a standard HIV genotype (Quest Diagnostics) within the last 5 years. 2006 AIDS research and therapy Result HIV K103N 155 160 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. An HLA-A2-restricted RT epitope including the lamivudine-associated M184V mutation has been characterized. 2006 AIDS research and therapy Result HIV M184V 68 73 RT 21 23 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. By this method, we found the region around mutation K103N to be reactive to T cells in 3 of the 10 subjects using 18-mer 103N mutant peptides in an initial screen. 2006 AIDS research and therapy Result HIV K103N 52 57 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. In another study, epitopes incorporating M41L, L74V, M184V and T215Y in RT were demonstrated by ELISPOT. 2006 AIDS research and therapy Result HIV L74V;M184V;M41L;T215Y 47;53;41;63 51;58;45;68 RT 72 74 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. In November 2005, K103N was detected on a standard genotype, at which time the viral load was 5,100 copies/ml. 2006 AIDS research and therapy Result HIV K103N 18 23 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. Such monotherapy can result in the rapid selection of K103N. 2006 AIDS research and therapy Result HIV K103N 54 59 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. The emergence of K103N and other drug resistant variants may be a dynamic process influenced by patient-specific anti-HIV CTL activity. 2006 AIDS research and therapy Result HIV K103N 17 22 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. The K103N mutation is a common cause of RT NNRTI drug resistance. 2006 AIDS research and therapy Result HIV K103N 4 9 NNRTI;RT 43;40 48;42 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. The tenth, subject 2, had a recent viral load of 2,000 copies/ml on a non-NNRTI based regimen and had evidence of circulating K103N by genotype 8 months prior to the study. 2006 AIDS research and therapy Result HIV K103N 126 131 NNRTI 74 79 16970827 Cytotoxic T cell recognition of an HIV-1 reverse transcriptase variant peptide incorporating the K103N drug resistance mutation. We next verified and characterized an epitope incorporating K103N in subject 6705A using PBMCs obtained 12 months after the initial ELISPOT assay. 2006 AIDS research and therapy Result HIV K103N 60 65 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. HIV-1 transcription induction by the Tat S16A mutant was approximately 75% that of WT Tat. 2006 Retrovirology Result HIV S16A 41 45 Tat;Tat 37;86 40;89 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. Neither S16A nor S46A mutants of Tat efficiently induced HIV-1 viral production. 2006 Retrovirology Result HIV S16A;S46A 8;17 12;21 Tat 33 36 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. the Tat S16A mutant and Tat S46A mutant were about 2-3 fold less phosphorylated. 2006 Retrovirology Result HIV S16A;S46A 8;28 12;32 Tat;Tat 4;24 7;27 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. These data indicate that the S16A and S46A mutations of Tat interfere with the ability of Tat to activate integrated HIV-1 provirus, and prevent Tat phosphorylation during one round of viral replication. 2006 Retrovirology Result HIV S16A;S46A 29;38 33;42 Tat;Tat;Tat 56;90;145 59;93;148 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. We determined whether mutations of Tat S16A and/or S46A have an effect on the ability of Tat to induce HIV-1 transcription from an integrated HIV-1 provirus. 2006 Retrovirology Result HIV S16A;S46A 39;51 43;55 Tat;Tat 35;89 38;92 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. while transactivation by the Tat S46A mutant was about 2 times lower than with the WT Tat. 2006 Retrovirology Result HIV S46A 33 37 Tat;Tat 29;86 32;89 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. For HIV-2/I73V[Env42S] a 9.3 fold increase in infection of TZM-LNCX2 cells compared to HIV-2[Env42] was observed, indicating the escape from Lv2-mediated restriction due the single amino acid change in the capsid protein. 2006 Retrovirology Result HIV I73V 10 14 Capsid;Env;Env 206;15;93 212;18;96 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. Furthermore, the only 2 fold increase of human TRIM5alpha mRNA in TZM-huTRIM5alpha cells is sufficient to confer a maximal restriction, even for the Lv2-insensitive HIV-2/I73V variant. 2006 Retrovirology Result HIV I73V 171 175 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. However, since the restriction of HIV-2/I73V[Env42S] on TZM-huTRIM5alpha cells was not changed compared to HIV-2[Env42S] one can conclude again that the Lv2-insensitive HIV-2/I73V remains restricted by human TRIM5alpha. 2006 Retrovirology Result HIV I73V;I73V 40;175 44;179 Env;Env 45;113 48;116 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. The challenge experiments with HIV-2 envelope protein Env42S pseudotyped HIV-2 particles (HIV-2[Env42S] and HIV-2/I73V[Env42S]) however confirmed again our previous observation that the Lv2-mediated restriction is entry route dependent. 2006 Retrovirology Result HIV I73V 114 118 Env;Env;Env;Env 37;54;96;119 45;57;99;122 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. The proviral ROD/A-DeltaenvRen plasmid (encoding isoleucine at position 73 of the capsid protein, shown to cause a Lv2-sensitive phenotype in the context of the molecular clone HIV-2MCR) was mutagenized to exchange isoleucine at position 73 to valine resulting in a Lv2-insensitive HIV2ROD variant (HIV-2/I73V) similar to HIV-2MCN . 2006 Retrovirology Result HIV I73V 305 309 Capsid 82 88 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. The viral capsid of HIV-1 is the main target for the antiviral effect, since certain mutations in the capsid protein (for example exchange of glycine to valine or alanine at position 89, G89V and G89A respectively) have been shown to confer resistance to TRIM5alpha mediated restriction. 2006 Retrovirology Result HIV G89A;G89V 196;187 200;191 Capsid;Capsid 10;102 16;108 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. This result is in agreement with earlier studies using CRFK cells expressing human TRIM5alpha after challenge with VSV-G pseudotyped HIV-2ROD but shows in addition that the Lv2-insensitive HIV-2/I73V remains restricted by human TRIM5alpha. 2006 Retrovirology Result HIV I73V 196 200 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. Using increasing infectious doses to challenge TZM-huTRIM5alpha cells a 3.4 and 4.8 fold restriction of VSV-G pseudotyped HIV-2 and HIV-2/I73V particles could be determined. 2006 Retrovirology Result HIV I73V 138 142 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Addition of T20 similarly reduces the fusogenicity of the GIA-SKY mutant (shaded bars), although the effect is more modest than that of the G431R reversion as we only used 20 ng/ml of T20. 2006 Retrovirology Result HIV G431R 140 145 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Evolution culture 2 showed a single amino acid change A221V in the C2 region of gp120. 2006 Retrovirology Result HIV A221V 54 59 gp120 80 85 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. G431R had the same effect on Env function in the context of wild-type and this mutant was totally inhibited by T20 as it does not contain the GIA T20-resistance mutation. 2006 Retrovirology Result HIV G431R 0 5 Env 29 32 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. G431R prevents an early gp41 conformational switch by counteracting hyper-fusogenicity. 2006 Retrovirology Result HIV G431R 0 5 gp41 24 28 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. However, when an alternative neutral amino acid (alanine which is the most analogous amino acid to the endogenous glycine; G431A) was introduced into the wild-type virus, replication and syncytia formation was re-established. 2006 Retrovirology Result HIV G431A 123 128 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Introduction of the negatively charged glutamic acid (G431E) completely abolished viral replication of the wild-type, both with and without T20, as observed in the context of the GIA-SKY virus. 2006 Retrovirology Result HIV G431E 54 59 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Introduction of the positive arginine (G431R) resulted in increased replication of the wild-type in the absence of T20. 2006 Retrovirology Result HIV G431R 39 44 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Most importantly, we also measured reduced Env function for the GIA-SKY-G431R revertant and this inhibition was also observed in the presence of T20. 2006 Retrovirology Result HIV G431R 72 77 Env 43 46 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Of most interest were evolution cultures 1, 4 and 5 that all acquired the same point mutation (G431R; all identical codon changes GGA-to-AGA), with no changes elsewhere in the Env protein. 2006 Retrovirology Result HIV G431R 95 100 Env 176 179 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. One change was observed in HR1 (Q567R) and 3 partial changes in the cytoplasmic tail (CT), N750N/T, Y762Y/C and Q799Q/H. 2006 Retrovirology Result HIV N750N;N750T;Q567R;Q799H;Q799Q;Y762C;Y762Y 91;91;32;112;112;100;100 98;98;37;119;119;107;107 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The combined results of the reduced sensitivity to sCD4 and increased sensitivity to D5-IgG1 suggest that the G431R mutation partially restores gp41 function of the Env protein by modulating the Env-CD4 interaction and 6-helix bundle formation. 2006 Retrovirology Result HIV G431R 110 115 gp41;Env;Env 144;165;195 148;168;198 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The G431R mutation is positioned in the C4 region of gp120, which plays a critical role in CD4 and co-receptor engagement. 2006 Retrovirology Result HIV G431R 4 9 gp120 53 58 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The G431R mutation rescues the T20-dependent virus. 2006 Retrovirology Result HIV G431R 4 9 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The G431R mutation was introduced into the GIA-SKY molecular clone and tested for its impact on viral replication and T20 resistance/dependence. 2006 Retrovirology Result HIV G431R 4 9 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The GIA-SKY-G431R revertant is resistant to T20 because it still contains the crucial T20-resistance mutation GIA. 2006 Retrovirology Result HIV G431R 12 17 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The GIA-SKY-G431R revertant was able to replicate in the absence of T20, confirming that the G431R mutation in gp120 is sufficient for the loss of the T20-dependent phenotype. 2006 Retrovirology Result HIV G431R;G431R 12;93 17;98 gp120 111 116 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. This result is consistent with the idea that both the exogenous T20 peptide and the endogenous G431R mutation have a moderating impact on the hyper-fusogenic GIA-SKY Env mutant. 2006 Retrovirology Result HIV G431R 95 100 Env 166 169 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. To test this, we measured the sensitivity of the wild-type (GIV-SNY) and revertant (GIA-SKY-G431R) viruses to the soluble form of CD4 (sCD4), using a standard virus replication assay to mimic the evolutionary setting. 2006 Retrovirology Result HIV G431R 92 97 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We constructed the molecular clone GIA-SKY-G431E and tested the ability of this mutant to replicate with and without T20. 2006 Retrovirology Result HIV G431E 43 48 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We further wanted to analyse the gp41 structure of GIA-SKY-G431R revertant and see if this virus is more sensitive to HR1 inhibitors, which would suggest that gp41 is in an "open" or "loose" conformation. 2006 Retrovirology Result HIV G431R 59 64 gp41;gp41 33;159 37;163 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We have shown that GIA-SKY replication in the absence of T20 is facilitated by the introduction of the G431R mutation in the gp120 C4 region. 2006 Retrovirology Result HIV G431R 103 108 gp120 125 130 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We measured dramatically reduced fusion activity (syncytia and luciferase counts) for the GIA-SKY-G431R revertant compared to the GIA-SKY mutant (black bars). 2006 Retrovirology Result HIV G431R 98 103 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We next tested the effect of G431R and G431E on the wild-type virus (GIV-SNY). 2006 Retrovirology Result HIV G431E;G431R 39;29 44;34 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We next tested the hypothesis that the G431R mutation in the GIA-SKY-G431R revertant represents a compensatory mutation that reduces or controls the structural transition in the GIA-SKY Env protein. 2006 Retrovirology Result HIV G431R;G431R 39;69 44;74 Env 186 189 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We propose that G431R negatively affects the Env/CD4 interaction as a means to prevent the abortive premature switch of the 6-helix bundle. 2006 Retrovirology Result HIV G431R 16 21 Env 45 48 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We therefore decided to investigate this revertant (GIA-SKY-G431R) in more detail. 2006 Retrovirology Result HIV G431R 60 65 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. We thus propose that the G431R mutation may offer a similar mechanistic check as the T20 peptide and preserve a pre-fusion intermediate necessary for correct gp41 conformational changes. 2006 Retrovirology Result HIV G431R 25 30 gp41 158 162 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. As a control, we used isogenic vectors expressing a mutant form of Vpr, pHR-VPR(R80A), wherein Vpr(R80A) is defective in induction of G2 arrest and apoptosis. 2006 PLoS pathogens Result HIV R80A;R80A 80;99 84;103 Vpr;Vpr;Vpr 67;76;95 70;79;98 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. Because the fusion with carboxyl-terminal GFP turns Vpr(R80A), a nonproaptotic protein, into an apoptotic one, it appears that the induction of apoptosis by Vpr-GFP represents a gain-of-function phenotype and is not representative of the biology of wild-type Vpr. 2006 PLoS pathogens Result HIV R80A 56 60 Vpr;Vpr;Vpr 52;157;259 55;160;262 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. Both Vpr-GFP and Vpr(R80A)-GFP were able to induce apoptosis. 2006 PLoS pathogens Result HIV R80A 21 25 Vpr;Vpr 5;17 8;20 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. Since Vpr(R80A) that is not fused to GFP is unable to induce apoptosis (Figures 1 and 2), we expected that the introduction of the R80A substitution in the Vpr-GFP fusion protein [Vpr(R80A)-GFP] would also result in a protein devoid of apoptosis induction. 2006 PLoS pathogens Result HIV R80A;R80A;R80A 10;131;184 14;135;188 Vpr;Vpr;Vpr 6;156;180 9;159;183 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. Surprisingly, Vpr(R80A)-GFP is also capable of inducing apoptosis. 2006 PLoS pathogens Result HIV R80A 18 22 Vpr 14 17 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. The Apo/G2M ratios were 0.83 for wild-type Vpr, 0.91 for Vpr(R77Q), and 0.92 for Vpr(I74A). 2006 PLoS pathogens Result HIV I74A;R77Q 85;61 89;65 Vpr;Vpr;Vpr 43;57;81 46;60;84 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. The levels of apoptosis, as judged by staining with FITC-VAD-FMK, were very similar between wild-type Vpr, Vpr(R77Q), and Vpr(I74A) and the levels of G2 arrest were also similar. 2006 PLoS pathogens Result HIV I74A;R77Q 126;111 130;115 Vpr;Vpr;Vpr 102;107;122 105;110;125 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. The Vpr mutants, R77Q and I74A, were separately constructed in the background of pHR-VPR-R (which encodes HIV-1NL4-3 vpr). 2006 PLoS pathogens Result HIV I74A;R77Q 26;17 30;21 Vpr;Vpr;Vpr 4;85;117 7;88;120 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. Therefore, we were unable to find any detectable differences in the functions of Vpr(R77Q) or Vpr(I74A) when compared with Vpr(R77). 2006 PLoS pathogens Result HIV I74A;R77Q 98;85 102;89 Vpr;Vpr;Vpr 81;94;123 84;97;126 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. These substitutions include Q3R, R77Q, and I47A. 2006 PLoS pathogens Result HIV I47A;Q3R;R77Q 43;28;33 47;31;37 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. To generate an appropriate control, we introduced the R80A mutation in the fusion construct, to generate Vpr(R80A)-GFP, and tested its ability to induce apoptosis (Figure 6C). 2006 PLoS pathogens Result HIV R80A;R80A 54;109 58;113 Vpr 105 108 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Changes at codon 436 (K436R/N) were present in only a few patient isolates and could not be evaluated. 2007 PLoS medicine Result HIV K436N;K436R 22;22 29;29 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. In IVS-1 there was an adjacent K436E amino acid change. 2007 PLoS medicine Result HIV K436E 31 36 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. In three of the experiments we observed an A431V amino acid substitution in the NC/p1 cleavage site, combined with known resistance substitutions in protease (V32I, M46I/L, I54V, V82A/F, and I84V). 2007 PLoS medicine Result HIV A431V;I54V;I84V;M46I;M46L;V32I;V82A;V82F 43;173;191;165;165;159;179;179 48;177;195;171;171;163;185;185 PR;NC 149;80 157;82 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Interestingly, all three viruses contained mutations in the C-terminal region of the viral gag gene at amino acid position 437 in the p1-coding region of gag (I437T/V). 2007 PLoS medicine Result HIV I437T;I437V 159;159 166;166 Gag;Gag 91;154 94;157 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. No amino acid changes in the viral protease sequence were observed, with the exception of a single K43T change in IVS-34. 2007 PLoS medicine Result HIV K43T 99 103 PR 35 43 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Of the clinical samples demonstrating a I437V substitution, 60% also presented a primary protease mutation at position 82 (p = 0.020), which indicates that this particular Gag mutation is also associated with a reduced virological response when present in combination with mutations in protease itself. 2007 PLoS medicine Result HIV I437V 40 45 PR;PR;Gag 89;286;172 97;294;175 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. The I437V substitution, in contrast, which was prevalent in 5% of all baseline isolates, was significantly associated with lack of virological response (p = 0.018 in univariate analysis; p = 0.031 in multivariate analysis). 2007 PLoS medicine Result HIV I437V 4 9 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. This A431V change, when introduced into a wild-type reference strain, conferred 3.8-fold reduced susceptibility to ritonavir (IC50 of 7.3 nM [wild-type] as compared to 28 nM [A431V mutant]). 2007 PLoS medicine Result HIV A431V;A431V 5;175 10;180 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. This analysis demonstrated a 37% prevalence of the A431V substitution at baseline, which was not associated with lack of virological response during subsequent PI therapy. 2007 PLoS medicine Result HIV A431V 51 56 PI 160 162 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. This resulted in the generation of three clones containing the following changes compared to wild-type HXB2: IVS-1 (436E+437T), IVS-32 (437V), and IVS-34 (437T and A15T in p6pol). 2007 PLoS medicine Result HIV A15T 164 168 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. This substitution, when introduced into a wild-type reference strain, did not cause an increase in resistance to RO033-4649 (IC50 of 27 nM for both wild-type and the K43T mutant). 2007 PLoS medicine Result HIV K43T 166 170 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. To test whether the PI resistance conferred by A431V was associated with a change in processing efficiency at this site, we investigated the relative turnover by wild-type protease of a decapeptide corresponding to either the wild-type HXB2 NC/p1 (ERQAN/FLGKI) or the mutant NC/p1 (ERQVN/FLGKI) cleavage site sequence. 2007 PLoS medicine Result HIV A431V 47 52 PR;NC;NC;PI 172;241;275;20 180;243;277;22 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. We observed an increased rate of peptide cleavage for the NC/p1 peptide containing the ritonavir resistance-associated A431V substitution (relative turnover of 0.18 [wild-type] as compared to 0.35 [for the mutant]; Table 2). 2007 PLoS medicine Result HIV A431V 119 124 NC 58 60 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. 4D) of distorted, aberrant and immature-like E98A virus particles as compared to the wild-type control may thus suggest that the E98 is important for proper protein conformation that is necessary for intermolecular CA-CA interactions. 2007 Retrovirology Result HIV E98A 45 49 Capsid;Capsid 215;218 217;220 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Although small percentage of virus with aberrant core was present, the majority of EM images of NL4-3 and E187G showed a mixture of both mature particles of normal morphology and immature particles. 2007 Retrovirology Result HIV E187G 106 111 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Briefly, cells were pre-incubated at 4 C for 1 h and exposed to equal amounts of DNaseI treated E98A or wild-type virus. 2007 Retrovirology Result HIV E98A 96 100 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. EM images of the three types of particles (NL4-3, E98A, and E187G) were categorized by the presence of three different core structures: aberrant, immature, and mature dense conical structure. 2007 Retrovirology Result HIV E187G;E98A 60;50 65;54 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. However, in contrast to the E187G and wild-type, we found that the E98A virions were non-infectious in permissive CD4 positive H9 cells. 2007 Retrovirology Result HIV E187G;E98A 28;67 33;71 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. In contrast, images of E98A showed mostly aberrant and immature particles. 2007 Retrovirology Result HIV E98A 23 27 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. In contrast, we found that viral DNA synthesis in cells infected with E98A virus was completely absent, suggesting that the E98A mutation interferes with an early stage in the viral replication cycle. 2007 Retrovirology Result HIV E98A;E98A 70;124 74;128 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. In this study, we investigated the effects associated with two single amino acid substitution mutations, the E98A and E187G respectively, having quite opposite intra molecular CA contacts with other CA residues. 2007 Retrovirology Result HIV E187G;E98A 118;109 123;113 Capsid;Capsid 176;199 178;201 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Since the E98A mutation is located C-terminal to the CypA-binding site and CypA has been suggested to disrupt CA-CA interactions following cell entry of the virus, we tested whether the reason for the diminished viral replication may be due to the lack of CypA incorporation in to the budding particle. 2007 Retrovirology Result HIV E98A 10 14 Capsid;Capsid 110;113 112;115 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Surprisingly, although proviral DNAs in H9 cells infected with E98A virus were not detected, a low level of Tat-induced luciferase activity was detected in a single-cell-cycle infectivity assay with TZM-bl cells. 2007 Retrovirology Result HIV E98A 63 67 Tat 108 111 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. The fact that WB analysis of the E98A mutant did not show any defect in proteolytic processing of Gag indicates that the mutation may affect the later stage of virus replication, possibly post-processing. 2007 Retrovirology Result HIV E98A 33 37 Gag 98 101 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Therefore, it is possible to speculate that the E98A mutation may rather be involved in inter-molecular CA-CA interaction or with other possible cellular factors involved in this process. 2007 Retrovirology Result HIV E98A 48 52 Capsid;Capsid 104;107 106;109 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. To elaborate this notion, the ability of mutant E98A virus binding and internalization was also determined on CD4+ TZM-bl cells, essentially as described elsewhere. 2007 Retrovirology Result HIV E98A 48 52 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Viral DNA production by E187G mutant virion was at a level similar to that for wild-type pNL4-3. 2007 Retrovirology Result HIV E187G 24 29 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. We determined by ELISA that cells transfected with the E98A mutant released approximately 15% higher p24 than cells transfected with the control vector. 2007 Retrovirology Result HIV E98A 55 59 p24 101 104 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. We observed that mutant E98A virions could bind and internalize into the target cells, indicating that there is no defect at this level of the virus replication cycle. 2007 Retrovirology Result HIV E98A 24 28 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. We observed that virion release was un-affected in both E98A and E187G mutants, as judged by the presence of the intermediate and fully processed Gag proteins. 2007 Retrovirology Result HIV E187G;E98A 65;56 70;60 Gag 146 149 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. After 21 passages (#21), two mutations, V38A and S113N, were also found in the gp120 encoding regions of the selected virus population; however, they were present in only 25% and 50% of the virus population, respectively. 2007 PLoS pathogens Result HIV S113N;V38A 49;40 54;44 gp120 79 84 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. At an IN concentration of 30 nM, the fluorescent signal of the IN-WT and IN-A128T enzymes increased upon increasing MBP-Delta325 concentrations (from 30 to 300 nM) until a plateau was reached. 2007 PLoS pathogens Result HIV A128T 76 81 IN;IN;IN 6;63;73 8;65;75 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Binding of IN-A128T and IN-E170G to MBP-Delta325 was reduced 2-fold and 3-fold, respectively. 2007 PLoS pathogens Result HIV A128T;E170G 14;27 19;32 IN;IN 11;24 13;26 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Both A128T and E170G IN Mutations Are Necessary and Together Sufficient for Viral Rescue. 2007 PLoS pathogens Result HIV A128T;E170G 5;15 10;20 IN 21 23 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Both C-terminal His-tagged WT INs (IN-WT) and IN containing the A128T mutation (IN-A128T) were able to pull down LEDGF/p75, MBP-IBD, and MBP-Delta325. 2007 PLoS pathogens Result HIV A128T;A128T 64;83 69;88 IN;IN;IN;IN 30;35;46;80 33;37;48;82 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. But upon overexpression of E170G-INs or mRFP-A128T/E170G-INs in HeLaP4 eGFP-Delta325 cells, cytoplasmic relocalisation was less explicit. 2007 PLoS pathogens Result HIV A128T;E170G;E170G 45;27;51 50;32;56 IN;IN 33;57 36;60 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Compared to the negative control, cross-correlation of eGFP-Delta325 or eGFP-LEDGF/p75(K150A) with WT mRFP-INs was readily detected (p < 0.01), indicating that both proteins interact with WT IN in the cytoplasm of the living cell (Figure 6). 2007 PLoS pathogens Result HIV K150A 87 92 IN;IN 107;191 110;193 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Confocal imaging suggests a decreased affinity of mRFP-A128T/E170G-IN for eGFP-Delta325 and LEDGF/p75. 2007 PLoS pathogens Result HIV A128T;E170G 55;61 60;66 IN 67 69 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Confocal Imaging Suggests a Decreased Affinity of mRFP-A128T/E170G-INs for eGFP-Delta325 and LEDGF/p75. 2007 PLoS pathogens Result HIV A128T;E170G 55;61 60;66 IN 67 70 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. HeLaP4 eGFP-Delta325 or HeLaP4 cells overexpressing eGFP-LEDGF/p75(K150A) were transfected with plasmids encoding WT or double mutant mRFP-INs. 2007 PLoS pathogens Result HIV K150A 67 72 IN 139 142 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. However, at the same MOI, NL4.3 A128T/E170G replication remained 10-fold lower. 2007 PLoS pathogens Result HIV E170G;A128T 38;32 43;37 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. However, mRFP-E170G-INs and mRFP-A128T/E170G-INs were more dispersed throughout the cell, although some residual nuclear localization could be observed. 2007 PLoS pathogens Result HIV A128T;E170G;E170G 33;14;39 38;19;44 IN;IN 20;45 23;48 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. However, replication levels of A128T/E170G virus were 10-fold lower in the Jurkat p75- cells, whereas no significant reduction of HIV-1 replication was observed in the BC Jurkat cells for any of the strains used. 2007 PLoS pathogens Result HIV A128T;E170G 31;37 36;42 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. However, this increase was significantly lower when the cells were infected with NL4.3 A128T/E170G virus. 2007 PLoS pathogens Result HIV E170G;A128T 93;87 98;92 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Identical results were obtained for mRFP-A128T-INs. 2007 PLoS pathogens Result HIV A128T 41 46 IN 47 50 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. In line with these results and to further strengthen our model that the A128T/E170 virus is still capable of interacting with LEDGF/p75 in vivo, we speculated that poor replication of the double mutant virus in WT cells could be rescued by overexpression of LEDGF/p75. 2007 PLoS pathogens Result HIV A128T 72 77 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. In the control HeLaP4 eGFP-Delta325 D366A cells, expressing interaction-defective eGFP-Delta325 (Figure S3B), the A128T/E170G fusion protein was also present throughout the cell, reflecting the loss of interaction. 2007 PLoS pathogens Result HIV A128T;E170G 114;120 119;125 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. In the control MT-4 eGFP cells, replication kinetics of the double mutant NL4.3 A128T/E170G was decreased 2-fold in comparison to the WT HIV-1 NL4.3. 2007 PLoS pathogens Result HIV E170G;A128T 86;80 91;85 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Indeed, upon overexpression of eGFP-LEDGF/p75, a remarkable relocalization of the mutant A128T/E170G IN to the nucleus was observed (Figure S3C), which suggests that high levels of LEDGF/p75 can overcome the loss in affinity. 2007 PLoS pathogens Result HIV A128T;E170G 89;95 94;100 IN 101 103 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Measuring total HIV-1 DNA after four passages pointed to a rescue in the number of proviruses in the 293T eGFP-Delta325 for the NL4.3 A128T/E170G virus in comparison with WT virus (Figure S2F). 2007 PLoS pathogens Result HIV E170G;A128T 140;134 145;139 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Moreover, viral replication of the NL4.3 A128T/E170G virus was inhibited 10-fold more than that of WT virus in MT-4 p75- cells. 2007 PLoS pathogens Result HIV E170G;A128T 47;41 52;46 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. No breakthrough of the mutant NL4.3 A128T/E170G virus was detected up to 10 d postinfection in MT-4 p75- cells (MOI 0.5) (Figure 7B). 2007 PLoS pathogens Result HIV E170G;A128T 42;36 47;41 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. No fluorescent signal above background could be detected for the IN-E170G and the IN-A128T/E170G mutants. 2007 PLoS pathogens Result HIV A128T;E170G;E170G 85;68;91 90;73;96 IN;IN 65;82 67;84 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. On the contrary, almost no interaction was detected with the E170G or A128T/E170G double mutation. 2007 PLoS pathogens Result HIV A128T;E170G;E170G 70;61;76 75;66;81 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. On the other hand, the number of 2-LTR circles decreased 4-fold for the NL4.3 A128T, NL4.3 E170G, and NL4.3 A128T/E170G virus compared with WT NL4.3 (Figure S2B). 2007 PLoS pathogens Result HIV E170G;A128T 114;108 119;113 LTR 35 38 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Replication kinetics of the double mutant NL4.3 A128T/E170G and the single mutant NL4.3 E170G were decreased 4-fold relative to the replication of WT NL4.3 as evaluated by p24 measurements. 2007 PLoS pathogens Result HIV E170G;A128T 54;48 59;53 p24 172 175 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Selection up to 21 passages (#21) in MT-4 eGFP-Delta325 cells resulted in a virus population with 100% of the strains containing both the A128T and the E170G mutation in the IN coding region. 2007 PLoS pathogens Result HIV A128T;E170G 138;152 143;157 IN 174 176 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Similar results were obtained with mRFP-A128T-INs. 2007 PLoS pathogens Result HIV A128T 40 45 IN 46 49 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Still, interaction of IN-A128T/E170G to MBP-Delta325 (300 nM) was reduced 8-fold compared with IN-WT. 2007 PLoS pathogens Result HIV A128T;E170G 25;31 30;36 IN;IN 22;95 24;97 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Substituting alanine for threonine at position 128, and performing a structure energy minimization, resulted in a slightly decreased binding affinity of IN for IBD, with an increase in binding energy from -68.02 to -61.03 kcal/mol. 2007 PLoS pathogens Result HIV T128A 13 50 IN 153 155 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Substituting glutamic acid for glycine at position 170 has a more drastic effect. 2007 PLoS pathogens Result HIV G170E 13 54 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The control cells overexpress the D366A mutant of eGFP-Delta325 known to be defective for interaction with HIV-1 IN. 2007 PLoS pathogens Result HIV D366A 34 39 IN 113 115 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The cross-correlation signal for the interaction of A128T/E170G mRFP-INs with eGFP-Delta325 was more affected than that for interaction with full-length LEDGF/p75, suggesting that the mutations in viral IN differentiate between Delta325 and full-length LEDGF/p75. 2007 PLoS pathogens Result HIV A128T;E170G 52;58 57;63 IN;IN 69;203 72;205 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The highly reduced interaction of MBP-Delta325 with IN-E170G and IN-A128T/E170G was analyzed in more detail with different IN and MBP-Delta325 concentrations using AlphaScreen technology (Figure 5B). 2007 PLoS pathogens Result HIV A128T;E170G;E170G 68;55;74 73;60;79 IN;IN;IN 52;65;123 54;67;125 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The IN-A128T enzyme displayed a 3-fold reduction in overall enzymatic activity. 2007 PLoS pathogens Result HIV A128T 7 12 IN 4 6 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The IN-E170G and the IN-A128T/E170G IN mutants both displayed a 2-fold reduction in overall enzymatic activity compared with IN-WT. 2007 PLoS pathogens Result HIV A128T;E170G;E170G 24;7;30 29;12;35 IN;IN;IN;IN 4;21;36;125 6;23;38;127 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Therefore, the K150A NLS mutation was introduced in LEDGF/p75 to overcome the nuclear localization, and measurements were done in the cytoplasm of the cell. 2007 PLoS pathogens Result HIV K150A 15 20 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. These cell lines were used to compare replication of WT NL4.3 virus and A128T/E170G NL4.3 virus (Figure S5B). 2007 PLoS pathogens Result HIV A128T;E170G 72;78 77;83 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. These data suggest a reduced affinity of mRFP-A128T/E170G-INs for the eGFP-Delta325 fusion protein. 2007 PLoS pathogens Result HIV A128T;E170G 46;52 51;57 IN 58 61 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. These results clearly indicate that the affinity of the double mutant IN-A128T/E170G to MBP-Delta325 is highly reduced. 2007 PLoS pathogens Result HIV A128T;E170G 73;79 78;84 IN 70 72 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. These selection experiments identified the mutations A128T, W131G, K156N, and G163E that mapped to the same regions in the IN gene. 2007 PLoS pathogens Result HIV A128T;G163E;K156N;W131G 53;78;67;60 58;83;72;65 IN 123 125 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. This experiment again suggests that poor replication of the IN mutants in WT cells is due to reduced affinity for LEDGF/p75 and that the A128T/E170 IN mutant virus still exploits LEDGF/p75 in vivo. 2007 PLoS pathogens Result HIV A128T 137 142 IN;IN 60;148 62;150 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. This suggests a reduced affinity of the mRFP-A128T/E170G-INs for LEDGF/p75. 2007 PLoS pathogens Result HIV A128T;E170G 45;51 50;56 IN 57 60 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. To analyze the rescue of viral replication by real-time quantitative PCR, 293T eGFP-Delta325 cells and control 293T eGFP-Delta325 D366A cells were infected with WT VSV NL4.3 or VSV NL4.3 A128T/E170G. 2007 PLoS pathogens Result HIV E170G;A128T 193;187 198;192 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. To evaluate the importance of the described mutations for the observed resistant phenotype, these mutations were cloned in the HIV-1 NL4.3 molecular clone (pNL4.3) as single or double mutants (pNL4.3 A128T, pNL4.3 E170G, and pNL4.3 A128T/E170G, respectively). 2007 PLoS pathogens Result HIV E170G;A128T 238;232 243;237 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. When a higher amount of IN (300 nM) was incubated with increasing MBP-Delta325 concentrations (from 30 to 300 nM), fluorescent signal could also be detected for the IN-E170G and the IN-A128T/E170G mutants. 2007 PLoS pathogens Result HIV A128T;E170G;E170G 185;168;191 190;173;196 IN;IN;IN 24;165;182 26;167;184 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Whereas the double mutant NL4.3 A128T/E170G rescued HIV-1 replication in MT-4 eGFP-Delta325 cells, the single mutants NL4.3 A128T and NL4.3 E170G could only partially restore viral replication. 2007 PLoS pathogens Result HIV E170G;A128T 38;32 43;37 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. By 12 weeks of treatment, K70E became undetectable prior to or coinciding with the establishment of the K65R mutation in 10 of the 12 animals. 2007 Retrovirology Result HIV K65R;K70E 104;26 108;30 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Coinciding with the detection of K70E and K65R mutants. 2007 Retrovirology Result HIV K65R;K70E 42;33 46;37 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Due to its high sensitivity for detecting low-frequency mutants, the real-time PCR assay detected the K65R mutation prior to its detection by population genotyping in 11 animals (table 1). 2007 Retrovirology Result HIV K65R 102 106 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Five weeks later, virus could be isolated again from PBMC, and this virus had the K65R and the same other RT mutations (including S68N) that were also detected during the viral rebound of the CD8+ depletion experiment (table 1). 2007 Retrovirology Result HIV K65R;S68N 82;130 86;134 RT 106 108 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. For all 12 animals, the K65R mutation became detectable in plasma viral RNA within 2 to 12 weeks of treatment (median time, 4 weeks). 2007 Retrovirology Result HIV K65R 24 28 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Further sequencing of the plasma RNA revealed that this K70E virus had also G196R, but not S68N; although it did not have I178M, this K70E virus therefore resembled the virus that was detected early after the start of tenofovir treatment (see table 1, week 24 isolate). 2007 Retrovirology Result HIV G196R;I178M;K70E;K70E;S68N 76;122;56;134;91 81;127;60;138;95 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Population sequencing of virus isolates from PBMC revealed that the 2 most frequent mutations that emerged sequentially early after tenofovir therapy were a lysine to glutamic acid mutation at codon 70 (K70E; AAA to GAA) followed by the K65R mutation (AAA to AGA)(table 1). 2007 Retrovirology Result HIV K65R;K70E;K70E 237;203;157 241;207;201 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Real-time PCR performed on the plasma sample collected 9 weeks after tenofovir withdrawal (which had a viral load of 910 RNA copies per ml) revealed K70E but no K65R. 2007 Retrovirology Result HIV K65R;K70E 161;149 165;153 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Real-time RT-PCR revealed that the plasma viral RNA at peak viremia consisted exclusively of K65R viral mutants, with no detection of the K70E mutation or wild-type sequence; this plasma viral RNA had also the S68N and G196R mutations; virus isolated from PBMC at peak viremia also had the expected K65R mutation, with relatively few other RT mutations compared to virus isolated 4 years earlier (table 1). 2007 Retrovirology Result HIV G196R;K65R;K65R;K70E;S68N 219;93;299;138;210 224;97;303;142;214 RT;RT 10;340 12;342 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Selection of K70E followed by K65R mutation in RT during prolonged tenofovir monotherapy. 2007 Retrovirology Result HIV K65R;K70E 30;13 34;17 RT 47 49 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Sequencing of mutation-specific amplicons revealed that the codon 68 mutations were associated with K65R sequences and not K70E. 2007 Retrovirology Result HIV K65R;K70E 100;123 104;127 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Similarly to our previous studies in tenofovir-treated SIVmac251-infected macaques, we investigated if this suppressed viremia of K65R virus in animal 30577 during prolonged tenofovir treatment was due to (i) a replication-impaired phenotype of the K65R mutant in this animal, (ii) strong CD8+ cell-mediated antiviral immune responses, and/or (iii) residual antiviral activity of the tenofovir regimen. 2007 Retrovirology Result HIV K65R;K65R 130;249 134;253 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. the codon 68 mutations may thus represent mutations that compensate for the replicative fitness cost of K65R, as has been suggested for HIV-1. 2007 Retrovirology Result HIV K65R 104 108 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The K65R mutation resulted in approximately 5-fold reduced in vitro susceptibility to tenofovir (data not shown). 2007 Retrovirology Result HIV K65R 4 8 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The mutations most commonly observed (sometimes transiently) after the detection of K65R included K20R (3 animals), M41L (3 animals), S68G/K/N (12 animals), K70H/N/T/Q (9 animals), W88S (6 animals), Y115F (9 animals), F116W (6 animals), V118I (3 animals), I178M (6 animals), L214F (11 animals), and K219Q/R/E/N/D/H/G (7 animals) (table 1). 2007 Retrovirology Result HIV F116W;I178M;K20R;K219D;K219E;K219G;K219H;K219N;K219Q;K219R;K65R;K70H;K70N;K70Q;K70T;L214F;M41L;S68G;S68K;S68N;V118I;W88S;Y115F 218;256;98;299;299;299;299;299;299;299;84;157;157;157;157;275;116;134;134;134;237;181;199 223;261;102;316;316;316;316;316;316;316;88;167;167;167;167;280;120;142;142;142;242;185;204 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The remaining animal, number 30577, became a long-term survivor with undetectable viremia, even though its virus had the K65R mutation in RT. 2007 Retrovirology Result HIV K65R 121 125 RT 138 140 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The tenofovir regimen was increased for most animals at 40 weeks of infection from 10 to 20 mg/kg to determine if higher drug levels would reduce viremia or select for other patterns of RT mutations that have previously been reported to give higher levels of in vitro resistance to tenofovir, such as T69S-insertion mutations. 2007 Retrovirology Result HIV T69S 301 305 RT 186 188 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Thus, continued tenofovir therapy was required to maintain optimal suppression of K65R and K70E viremia in this animal. 2007 Retrovirology Result HIV K65R;K70E 82;91 86;95 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V75I/L, E194K, G196R, L214F) were already present in some viruses obtained prior to tenofovir therapy, and most have previously been described in RT-SHIV isolates obtained from untreated macaques. 2007 Retrovirology Result HIV E194K;G196R;L214F;V75I;V75L 8;15;22;0;0 13;20;27;6;6 RT 146 148 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. When both K65R and K70E were detected in plasma viral RNA samples, direct sequencing of the mutation-specific real-time PCR amplicons demonstrated that the 2 mutations were on separate genomes. 2007 Retrovirology Result HIV K65R;K70E 10;19 14;23 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. While population genotyping of DNA from PBMC-derived virus isolates detected K70E mutants in only 10 animals, the real-time PCR method detected K70E mutants in plasma RNA of all 12 animals within 1 to 4 weeks (median 2 weeks) of tenofovir treatment. 2007 Retrovirology Result HIV K70E;K70E 77;144 81;148 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. A62V, K65R, and Y115F are mutations that cluster with Q151M but may also occur with Type II (but not Type I) TAMs. 2007 PLoS computational biology Result HIV K65R;Q151M;Y115F;A62V 6;54;16;0 10;59;21;4 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Among the top 40 associated mutation pairs, there were only three positive associations between Type I and II TAMs (M41L, L210W, and T215Y with D67N). 2007 PLoS computational biology Result HIV D67N;L210W;M41L;T215Y 144;122;116;133 148;127;120;138 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. D67N is a Type II TAM that can also occur with Type I TAMs, and it therefore occurs between Type I TAMs and Type II TAMs in terms of the second principal component. 2007 PLoS computational biology Result HIV D67N 0 4 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Finally, the lower-left part of the figure contains a cluster with seven of the 11 mutations recently reported to be associated with phenotypic and clinical resistance to the newest PI, darunavir (V32I, L33F, I47V, I50V, I54L/M, and L76V). 2007 PLoS computational biology Result HIV I47V;I50V;I54L;I54M;L33F;L76V;V32I 209;215;221;221;203;233;197 213;219;227;227;207;237;201 PI 182 184 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. For example, M46I/L were each significantly associated with L10I, L24I, V32I, L33F, I54V, V82A, and L90M. 2007 PLoS computational biology Result HIV I54V;L10I;L24I;L33F;L90M;M46I;M46L;V32I;V82A 84;60;66;78;100;13;13;72;90 88;64;70;82;104;19;19;76;94 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. For example, the first row shows that among persons with both I54V and V82A in whom an earlier sequence contained only one of these two mutations was available, I54V occurred first in nine (26%) of 34 people, and V82A occurred first in 25 (74%) of 34 people (p < 0.01). 2007 PLoS computational biology Result HIV I54V;I54V;V82A;V82A 62;161;71;213 66;165;75;217 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. However, M46I was uniquely associated with F53L, G73S/T, V82F/T, I84V, and N88S. 2007 PLoS computational biology Result HIV F53L;G73S;G73T;I84V;M46I;N88S;V82F;V82T 43;49;49;65;9;75;57;57 47;55;55;69;13;79;63;63 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. I54V was significantly associated with L10F, L24I, L33F, M46I/L, G48V, F53L, V82A/F/T, I84V, and L90M. 2007 PLoS computational biology Result HIV F53L;G48V;I84V;L10F;L24I;L33F;L90M;M46I;M46L;V82A;V82F;V82T;I54V 71;65;87;39;45;51;97;57;57;77;77;77;0 75;69;91;43;49;55;101;63;63;85;85;85;4 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. In addition to the five accessory mutations in Table 2 (K43E, E44D, V118I, H208Y, and D218E), other NRTI mutations that consistently followed TAMs included the known treatment-selected mutations T69D and T69N. 2007 PLoS computational biology Result HIV D218E;E44D;H208Y;K43E;T69D;T69N;V118I 86;62;75;56;195;204;68 91;66;80;60;199;208;73 NRTI 100 104 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. In contrast, I54L/M were significantly associated only with L33F, M46I, I47V, I84V, and L90M. 2007 PLoS computational biology Result HIV I47V;I54L;I54M;I84V;L33F;L90M;M46I 72;13;13;78;60;88;66 76;19;19;82;64;92;70 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. In contrast, the accessory mutation L63P preceded L90M in 160 of 172 persons, and the accessory mutations L10I and A71V preceded the major mutation I84V in 51 of 59 and 35 of 38 persons, respectively. 2007 PLoS computational biology Result HIV A71V;I84V;L10I;L63P;L90M 115;148;106;36;50 119;152;110;40;54 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. In contrast, the fourth row shows that among persons with both A71V and L90M, each of the mutations was as likely to occur first (26 of 51 versus 25 of 51; p = NS). 2007 PLoS computational biology Result HIV A71V;L90M 63;72 67;76 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. In contrast, two less common mutations at this position (K219N/R) were positively associated with Type I TAMs. 2007 PLoS computational biology Result HIV K219N;K219R 57;57 64;64 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. K219Q/E were Type II TAMs that cluster with other Type II TAMs. 2007 PLoS computational biology Result HIV K219E;K219Q 0;0 7;7 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. L74V was associated with the NNRTI-resistance mutations L100I, K103N, and Y181C, whereas L74I was associated with M41L. 2007 PLoS computational biology Result HIV K103N;L100I;L74I;M41L;Y181C;L74V 63;56;89;114;74;0 68;61;93;118;79;4 NNRTI 29 34 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. N88D was positively associated with D30N and negatively associated with M46I, whereas N88S was negatively associated with D30N and positively associated with M46I. 2007 PLoS computational biology Result HIV D30N;D30N;M46I;M46I;N88S;N88D 36;122;72;158;86;0 40;126;76;162;90;4 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Positively associated mutation pairs consisted primarily of Type I or II thymidine analog mutations (TAMs; as defined in Methods); accessory NRTI mutations that occurred in combination with Type I or II TAMs (K43E, E44D, V118I, H208Y, D218E); and Q151M-associated mutations (V75I, F77L, F116Y). 2007 PLoS computational biology Result HIV D218E;E44D;F116Y;F77L;H208Y;K43E;Q151M;V118I;V75I 235;215;287;281;228;209;247;221;275 240;219;292;285;233;213;252;226;279 NRTI 141 145 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. T69D was associated with both Type I and Type II TAMs, whereas T69N was associated only with Type II TAMs. 2007 PLoS computational biology Result HIV T69N;T69D 63;0 67;4 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The first principal component accounted for 10% of the total inertia and separates the nelfinavir-resistance mutations D30N and N88D from the main group of PI-resistance mutations. 2007 PLoS computational biology Result HIV D30N;N88D 119;128 123;132 PI 156 158 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The first principal component accounts for 13% of the total inertia and separates the TAMs from the Q151M-associated mutations, whereas the second principal component accounts for 9% of the total inertia and separates the Type I and Type II TAMs. 2007 PLoS computational biology Result HIV Q151M 100 105 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The major mutation L90M preceded the accessory mutation G73S in 31 of 34 persons for whom temporal data were available. 2007 PLoS computational biology Result HIV G73S;L90M 56;19 60;23 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The mutations included in this analysis were the 22 positively associated mutations in Table 1 and 13 additional clinically relevant PI-resistance mutations (L10F, V32I, L33F, I47V, I50V/L, F53L, I54L/M, Q58E, L76V, V82T, and N88S). 2007 PLoS computational biology Result HIV F53L;I47V;I50L;I50V;I54L;I54M;L10F;L33F;L76V;N88S;Q58E;V32I;V82T 190;176;182;182;196;196;158;170;210;226;204;164;216 194;180;188;188;202;202;162;174;214;230;208;168;220 PI 133 135 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The mutations included in this analysis were the 23 positively associated mutations in Table 2 and 11 additional clinically relevant NRTI-resistance mutations (K65R, A62V, T69ins, L74I/V, V75M, Y115F, M184V, and K219R/E/N). 2007 PLoS computational biology Result HIV A62V;K219E;K219N;K219R;K65R;L74I;L74V;M184V;T69ins;V75M;Y115F 166;212;212;212;160;180;180;201;172;188;194 170;221;221;221;164;186;186;206;178;192;199 NRTI 133 137 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The non-TAM mutations, M184V and L74V, demonstrated no clustering with other NRTI-associated mutations. 2007 PLoS computational biology Result HIV L74V;M184V 33;23 37;28 NRTI 77 81 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The second principal component accounted for 7% of the total inertia and separates V82A-associated mutations (I54V, L24I, and M46L) from L90M-associated mutations (M46I, G73S, and I84V). 2007 PLoS computational biology Result HIV G73S;I54V;I84V;L24I;L90M;M46I;M46L;V82A 170;110;180;116;137;164;126;83 174;114;184;120;141;168;130;87 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The strongest significant association between an NRTI and an NNRTI mutation was between L74V and Y181C (J = 0.17, Z = 8.9, unadjusted p < 1 x 10-11). 2007 PLoS computational biology Result HIV L74V;Y181C 88;97 92;102 NNRTI;NRTI 61;49 66;53 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. The Type I TAM, T215Y, clustered with other Type I TAMs, whereas the Type II TAM, T215F, clustered with other Type II TAMs. 2007 PLoS computational biology Result HIV T215F;T215Y 82;16 87;21 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. V75I was associated with Q151M-associated mutations, whereas V75M was positively associated with the Type I TAMs. 2007 PLoS computational biology Result HIV Q151M;V75M;V75I 25;61;0 30;65;4 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. As a negative control, we performed a parallel experiment in which pHR-Vpr(R80A) was replaced by a vector expressing GFP only (see Additional file 3 for cell cycle profile data). 2007 Virology journal Result HIV R80A 75 79 Vpr 71 74 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Cells were either incubated with epoxomicin, DMSO, or transfected with Ub(K48R) or empty vector. 2007 Virology journal Result HIV K48R 74 78 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Co-transduction of even small amounts of Vpr(R80A) vector resulted in strong reduction of Vpr induced G2 arrest, whereas transduction with equivalent infectious units of pHR-GFP had no effect. 2007 Virology journal Result HIV R80A 45 49 Vpr;Vpr 41;90 44;93 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. If this were true, then Vpr(R80A) should act as a dominant-negative mutant, and interfere with the function of wild-type Vpr by competing for binding to DCAF1. 2007 Virology journal Result HIV R80A 28 32 Vpr;Vpr 24;121 27;124 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. In agreement with the epoxomicin results, over-expression of Ub(K48R) also very effectively abolished the induction of G2 arrest in Vpr-expressing cells (Figure 1). 2007 Virology journal Result HIV K48R 64 68 Vpr 132 135 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. In order to generate a more appropriate negative control for IP experiments, we constructed the mutation Vpr(Q65R), which disrupts a leucine-rich region required for binding to DCAF1. 2007 Virology journal Result HIV Q65R 109 113 Vpr 105 108 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. In separate experiments, we also detected an interaction between Vpr - and also Vpr(R80A) - and myc-tagged cullin 4a (data not shown). 2007 Virology journal Result HIV R80A 84 88 Vpr;Vpr 65;80 68;83 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Our results are inconsistent with the previous model in that (a) the function of the DDB1/DDB2 complex in recognizing DNA damage does not require DCAF1, whereas Vpr induced G2 arrest does; (2) Vpr is unable to directly associate with DDB1; instead, Vpr binds to DCAF1; (3) the ability of the DDB1/DDB2 complex to bind to damaged DNA does not require a functional UPS, whereas Vpr function does; and (4) Vpr(R80A), although incapable of inducing G2 arrest, still interacts with DDB1. 2007 Virology journal Result HIV R80A 407 411 Vpr;Vpr;Vpr;Vpr;Vpr 161;193;249;376;403 164;196;252;379;406 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Since the inactive mutant, Vpr(R80A), binds to DDB1 and DCAF1 with similar efficiency as wild-type Vpr, we conclude that binding to DCAF1/DDB1 is not sufficient for Vpr function. 2007 Virology journal Result HIV R80A 31 35 Vpr;Vpr;Vpr 27;99;165 30;102;168 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. The inability of Vpr(R80A) to induce G2 arrest could, therefore, be due to lack of recruitment of a potential target for ubiquitination. 2007 Virology journal Result HIV R80A 21 25 Vpr 17 20 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Thus, we constructed the double mutant, Vpr(Q65R, R80A). 2007 Virology journal Result HIV Q65R;R80A 44;50 48;54 Vpr 40 43 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. To test the previous idea, we co-infected cells with a constant amount of pHR-Vpr vector (MOI = 1.0) and decreasing amounts of Vpr(R80A) (MOIs of 1, 0.5 and 0.25), and then assessed the cell cyle profile in these cultures (Figure 4). 2007 Virology journal Result HIV R80A 131 135 Vpr;Vpr 78;127 81;130 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Vpr(Q65R, R80A) did not behave as a dominant-negative protein (Figure 4; see also Additional file 3). 2007 Virology journal Result HIV Q65R;R80A 4;10 8;14 Vpr 0 3 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Vpr(Q65R, R80A) was, as expected, unable to bind DCAF (data not shown), or to induce G2 arrest (Figure 4). 2007 Virology journal Result HIV Q65R;R80A 4;10 8;14 Vpr 0 3 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Vpr(Q65R) failed to associate with DDB1 (Figure 3, panel B, lane 8), DCAF1 (Figure 3, panel D, lane 6), and also failed to induce G2 arrest (Figure 4). 2007 Virology journal Result HIV Q65R 4 8 Vpr 0 3 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Vpr(R80A) acts as a dominant-negative protein. 2007 Virology journal Result HIV R80A 4 8 Vpr 0 3 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Vpr(R80A), while unable to induce G2 arrest, has an intact LR domain, which explains its ability to bind DCAF1 (Figure 3). 2007 Virology journal Result HIV R80A 4 8 Vpr 0 3 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. We demonstrated co-immunoprecipitation of Vpr and, separately, Vpr(R80A), with DDB1 (Figure 3, panel B, lanes 6 and 7). 2007 Virology journal Result HIV R80A 67 71 Vpr;Vpr 42;63 45;66 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. We resorted to two different methods of proteasome inhibition: incubation with epoxomicin, and over-expression of a dominant-negative ubiquitin mutant, Ub(K48R) that blocks formation of polyubiquitin chain conjugates. 2007 Virology journal Result HIV K48R 155 159 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. We then hypothesized that if the dominant-negative activity of Vpr(R80A) stems from its ability to bind to DCAF1, then introducing the Q65R mutation in Vpr(R80A) would abolish the dominant-negative activity. 2007 Virology journal Result HIV Q65R;R80A;R80A 135;67;156 139;71;160 Vpr;Vpr 63;152 66;155 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. We transfected a Flag-DCAF1 construct along with either HA-Vpr or HA-Vpr(R80A), a Vpr mutant that is incapable of inducing G2 arrest and, 48 hours later, we immunoprecipitated Flag-DCAF1 from cell extracts. 2007 Virology journal Result HIV R80A 73 77 Vpr;Vpr;Vpr 59;69;82 62;72;85 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. When immunoprecipitates obtained with anti-HA antibody (specific for HA-Vpr) were analyzed by WB for the presence of Flag-DCAF1 (Figure 3, panel A), the presence of a reactive band of the expected molecular weight was evident both for HA-Vpr(R80A) (lane 5) and HA-Vpr (lane 6). 2007 Virology journal Result HIV R80A 242 246 Vpr;Vpr;Vpr 72;238;264 75;241;267 17668043 Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals. Importantly, HIV-1 NL4-3 replication in these mice was genetically stable over the 21-day infection period; there was no evidence of the RT M184V substitution in viral RNA amplified by RT-PCR and sequenced from 32 of 32 Thy/Liv implants collected from mice treated with 3TC in these seven experiments (data not shown). 2007 PloS one Result HIV M184V 140 145 RT;RT 137;185 139;187 17668043 Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals. We reported the activity of the 3TC analog dOTC against 3TC-resistant HIV-1 NL4-3/M184V in the SCID-hu Thy/Liv model. 2007 PloS one Result HIV M184V 82 87 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. A limited number of immature-like viruses and occasionally mature-like viruses but with aberrant cores were observed with the D51E mutant. 2007 Retrovirology Result HIV D51E 126 130 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Additionally, the D51N virions showed a large pool of intra-vesicular viruses that were deficient of the electron dense core structure. 2007 Retrovirology Result HIV D51N 18 22 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. As shown in Figure 4, an increase in sample turbidity was observed for both D51N and D51E mutant CAp24 proteins. 2007 Retrovirology Result HIV D51E;D51N 85;76 89;80 Capsid 97 99 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. As shown in Figure 5, long tubular structures were observed in both D51N and D51E mutant CAp24 proteins induced by addition of 2.0 M NaCl solution. 2007 Retrovirology Result HIV D51E;D51N 77;68 81;72 Capsid 89 91 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. As shown in Figure 6A, the CAp24 antigen levels in the culture supernatant of D51N and D51Q transfected cells were negligible in all three cell lines, whereas the virus production of the D51E mutant was reduced by 2- to 6-fold as compared to the wild type. 2007 Retrovirology Result HIV D51E;D51N;D51Q 187;78;87 191;82;91 Capsid 27 29 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Further reduction or absence of cell-associated CAp24 of the D51N and D51Q mutants was observed in both 293T and COS7 cells. 2007 Retrovirology Result HIV D51N;D51Q 61;70 65;74 Capsid 48 50 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. However, the level of this protein in both D51N and D51Q mutants was significantly reduced relative to the wild type and D51E mutant, correlating with the lower intracellular CAp24 levels. 2007 Retrovirology Result HIV D51E;D51N;D51Q 121;43;52 125;47;56 Capsid 175 177 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. In contrast, no structure that resembled CAp24 tubular formation was observed with the D51Q mutant CAp24 protein under the same conditions. 2007 Retrovirology Result HIV D51Q 87 91 Capsid;Capsid 41;99 43;101 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. In marked contrast, the rate of sample turbidity increase for the D51Q mutant CAp24 was higher than for the wild type control. 2007 Retrovirology Result HIV D51Q 66 70 Capsid 78 80 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. The D51N and D51Q mutant virions showed mostly particles devoid of the typical HIV-1 core structure (Figure 9, panel D51N and D51Q). 2007 Retrovirology Result HIV D51N;D51N;D51Q;D51Q 4;117;13;126 8;121;17;130 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. The relative intracellular level of the Pr55Gag precursor in all mutants was comparable to that of the wild type, whilst the D51N and D51Q mutants displayed somewhat reduced levels of the CAp24. 2007 Retrovirology Result HIV D51N;D51Q 125;134 129;138 Capsid;PR 188;40 190;42 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. We investigated the effects of three HIV-1 CAp24 mutants carrying the D51N, D51E, and D51Q mutations for viral protein expression by initially transfecting HeLa-tat cells. 2007 Retrovirology Result HIV D51E;D51N;D51Q 76;70;86 80;74;90 Tat;Capsid 161;43 164;45 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Whereas no CAp24 was detected with the D51N mutant, significantly reduced level of this protein was observed with the D51Q mutant in both 293T and COS7 cells. 2007 Retrovirology Result HIV D51N;D51Q 39;118 43;122 Capsid 11 13 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Whereas the D51Q mutant displayed a slightly reduced amount of CAp24, the level of processed CAp24 proteins in the D51N mutant was significantly reduced relative to the wild type and the D51E CAp24 mutant. 2007 Retrovirology Result HIV D51E;D51N;D51Q 187;115;12 191;119;16 Capsid;Capsid;Capsid 63;93;192 65;95;194 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. While the Tat-induced luciferase activity could not be detected in cells infected with mutant D51N and D51Q virions, only a subtle amount of luciferase activity was observed repeatedly in cells infected with the D51E virions (Figure 7). 2007 Retrovirology Result HIV D51E;D51N;D51Q 212;94;103 216;98;107 Tat 10 13 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. With HeLa-tat III cells (Figure 3), the levels of CAp24 detected with the D51N and D51Q were largely identical with those in HeLa-tat cells detected with a rabbit anti-CAp24 antibody (Figure 2B). 2007 Retrovirology Result HIV D51N;D51Q 74;83 78;87 Tat;Tat;Capsid;Capsid 10;130;50;168 13;133;52;170 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. A strong recognition of the KK10 L6M variant was also detected by cross-sectional analysis of five additional subjects with chronic HIV-1 infection harboring the L6M mutation in their autologous viral sequence. 2007 The Journal of experimental medicine Result HIV L6M 162 165 HIV infections 124 147 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Although the use of recombinant ILT4 in a dimer form precludes assessment of the affinity between HLA-B2705 and naturally occurring, monomeric ILT4, this observation corresponds to a sixfold increase in apparent affinity for the interaction involving the L6M mutation relative to that of the WT. 2007 The Journal of experimental medicine Result HIV L6M 255 258 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Because stimulation with L6M pentamers had an inhibitory effect on DC maturation, we subsequently determined whether peptide-loaded APCs would have a similar effect. 2007 The Journal of experimental medicine Result HIV L6M 25 28 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. In contrast, the KK10 L6M variant and the variants with combined mutations at position 2 and 6 (R2K/L6M, R2T/L6M) were only very poorly recognized during primary HIV-1 infection compared with either the KK10 WT sequence or the KK10 variants with amino acid changes at position 2 only. 2007 The Journal of experimental medicine Result HIV L6M;L6M;R2K;R2T 100;109;96;105 103;112;99;108 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Mutations at position 2 in this epitope, which typically occur late during the disease and subsequent to the L6M mutation, are also strongly associated with HLA-B2705 expression and have been shown to reduce binding to HLA-B2705. 2007 The Journal of experimental medicine Result HIV L6M 109 112 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. The most frequent HLA-B2705-associated mutation in this epitope involves an L to M amino acid substitution at position 6 (L6M), which does not substantially affect the binding avidity to the restricting HLA molecule, peptide processing, or viral fitness, but may alter the interaction with TCR contact residues. 2007 The Journal of experimental medicine Result HIV L6M;L6M 122;76 125;120 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. The recognition of the L6M variant in these individuals was at least partially mediated by newly generated KK10-specific CD8+ T cell clones with cross-reactive TCRs that had almost identical capacities to recognize the KK10 WT and the KK10 L6M variant. 2007 The Journal of experimental medicine Result HIV L6M 23 26 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. To confirm an antigenic peptide variant-specific binding mechanism between ILT4 and HLA-B27-KK10 complexes, these receptor-ligand interactions were further analyzed using recombinant proteins (ILT4-IgG dimers and HLA-B2705 KK10 WT/L6M tetramers) and surface plasmon resonance (SPR) experiments. 2007 The Journal of experimental medicine Result HIV L6M 231 234 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. To determine if the B2705-KK10 L6M-mediated inhibition of DC maturation would translate into functional impairments of these cells, we next used MDDCs matured in the presence of HLA-B2705-KK10 WT or L6M pentamers to perform mixed lymphocyte reactions with CFSE-labeled allogenic T cells. 2007 The Journal of experimental medicine Result HIV L6M 199 202 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. To determine if the L6M mutation in the KK10 epitope, in addition to altering binding to the TCR, also affects recognition by other HLA class I receptors expressed on lymphocytes, monocytes/macrophages, or DCs, we stained PBMCs from chronically HIV-1-infected, treatment-naive, and HLA-B2705- individuals with HLA-B2705 pentamers refolded with the KK10 WT or KK10 L6M peptides. 2007 The Journal of experimental medicine Result HIV L6M 20 23 HIV infections 245 259 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Using interferon gamma ELISPOT assays, we found that in addition to the KK10 WT peptide, KK10 variants with amino acid substitutions at position 2 (R2K or R2T) were still recognized by CD8+ T cells during primary infection, although the avidity of recognition decreased by ~10-fold and might be weaker when the variant peptide is naturally presented. 2007 The Journal of experimental medicine Result HIV R2K;R2T 148;155 152;158 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Again, both Vpr-L23F and -K27M mutants failed to concentrate at the NE and predominantly localized in the cytoplasm as a diffuse staining. 2007 Retrovirology Result HIV K27M;L23F 26;16 30;20 Vpr 12 15 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. As controls, the Vpr-R80A and -R90K variants, which still accumulated at the NE. 2007 Retrovirology Result HIV R80A;R90K 21;31 25;35 Vpr 17 20 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. As previously reported, Vpr-F34I displayed a nucleocytoplasmic distribution. 2007 Retrovirology Result HIV F34I 28 32 Vpr 24 27 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. both Vpr-L23F and -K27M were efficiently packaged into purified virions, but a slight difference in the level of incorporation was repeatedly observed. 2007 Retrovirology Result HIV K27M;L23F 19;9 23;13 Vpr 5 8 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Consistent with previous observations, the Vpr-F34I mutant was partially altered for the G2-arrest activity, while the Vpr-A30L mutant was completely defective. 2007 Retrovirology Result HIV A30L;F34I 123;47 127;51 Vpr;Vpr 43;119 46;122 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Conversely, the levels of replication of the Vpr-L23F and -K27M mutant viruses were similar to that of the wt virus in MDMs from another donor. 2007 Retrovirology Result HIV K27M;L23F 59;49 63;53 Vpr 45 48 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. DNA Sequencing of clone 11 revealed 3 substitutions within the VprLai primary sequence (Leu23Phe, Leu67Gln and Arg73Gly), while clone 35 contained a single substitution (Lys27Met). 2007 Retrovirology Result HIV K27M;L23F;L67Q;R73G 170;88;98;111 178;96;106;119 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Finally, the relationship between the Vpr docking at the NE and HIV-1 replication in non-dividing cells was explored by analyzing the impact of the hCG1-binding deficient Vpr-L23F and -K27M mutations on viral replication in primary macrophages. 2007 Retrovirology Result HIV K27M;L23F 185;175 189;179 Vpr;Vpr 38;171 41;174 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. In contrast to the wt Vpr-GFP fusion, both Vpr-L23F and -K27M equally distributed between the cytoplasm and the nucleus. 2007 Retrovirology Result HIV K27M;L23F 57;47 61;51 Vpr;Vpr 22;43 25;46 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. In contrast with published observations, we found that Vpr-A30L was distributed between the nucleus and the cytoplasm and failed to concentrated at the NE. 2007 Retrovirology Result HIV A30L 59 63 Vpr 55 58 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. In contrast, other Vpr mutants with substitutions in the third alpha-helix or in the C-terminal flexible basic region of the protein, such as Vpr-W54R, -R80A and -R90K, were concentrated at the NE as efficiently as the wt Vpr-GFP fusion. 2007 Retrovirology Result HIV R80A;R90K;W54R 153;163;146 157;167;150 Vpr;Vpr;Vpr 19;142;222 22;145;225 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. In contrast, the L67Q and R73G Vpr mutants still interacted with both hCG1 and UNG2. 2007 Retrovirology Result HIV L67Q;R73G 17;26 21;30 Vpr 31 34 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. In order to explore whether substitutions in the first alpha-helix had a general impact on the localization of Vpr, the cellular distribution of two other Vpr mutants (Vpr-A30L and -F34I) was also analyzed. 2007 Retrovirology Result HIV A30L;F34I 172;182 176;186 Vpr;Vpr;Vpr 111;155;168 114;158;171 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Interestingly, the Vpr-induced pro-apoptotic activity of all the Vpr mutants, including Vpr-L23F and -K27M, strictly paralleled the results obtained in the cell cycle experiments (compare. 2007 Retrovirology Result HIV K27M;L23F 102;92 106;96 Vpr;Vpr;Vpr 19;65;88 22;68;91 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. one can note that the levels of incorporation were sufficient, at least in donor 3, for efficient replication of the Vpr-L23F and -K27M mutant viruses. 2007 Retrovirology Result HIV K27M;L23F 131;121 135;125 Vpr 117 120 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Similar replication kinetics were observed for wt HIV-1YU-2, HIV-1DeltaVpr, and the Vpr-L23F and -K27M mutant viruses (data not shown). 2007 Retrovirology Result HIV K27M;L23F 98;88 102;92 Vpr 84 87 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Since a functional link was reported between the targeting at the NE and the Vpr-induced cell cycle arrest, the G2-arrest activity of the Vpr-L23F and Vpr-K27M mutants was first assessed in T lymphocytes. 2007 Retrovirology Result HIV K27M;L23F 155;142 159;146 Vpr;Vpr;Vpr 77;138;151 80;141;154 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. The L23F and K27M mutations were thus introduced into the vpr gene of the macrophage-tropic HIV-1YU-2 molecular clone. 2007 Retrovirology Result HIV K27M;L23F 13;4 17;8 Vpr 58 61 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. the L23F and K27M substitutions were sufficient to abrogate hCG1 binding without significant alteration of binding to UNG2. 2007 Retrovirology Result HIV K27M;L23F 13;4 17;8 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. The Vpr-L23F and -K27M mutant viruses exhibited differential replication abilities according to the donor. 2007 Retrovirology Result HIV K27M;L23F 18;8 22;12 Vpr 4 7 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. The Vpr-L23F mutant was affected but retained about 50% of the activity measured for the wt protein, while the Vpr-K27M mutant was more severely affected leading to a residual G2-arrest activity. 2007 Retrovirology Result HIV K27M;L23F 115;8 119;12 Vpr;Vpr 4;111 7;114 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. These results reveal that the L23F and K27M Vpr variants are specifically altered for the binding to hCG1. 2007 Retrovirology Result HIV K27M;L23F 39;30 43;34 Vpr 44 47 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Used as controls, the VprR90K mutant, which is known to abolish Vpr-induced G2-arrest, still bound both to hCG1 and UNG2, while the W54R mutant, which is deficient for binding to UNG2, still interacted with hCG1. 2007 Retrovirology Result HIV W54R 132 136 Vpr;Vpr 22;64 25;67 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. While these results confirm that the absence of Vpr expression consistently affects HIV-1 replication in primary macrophages, the Vpr-L23F and -K27M mutations lead to a replication defect in macrophages from most of the donors. 2007 Retrovirology Result HIV K27M;L23F 144;134 148;138 Vpr;Vpr 48;130 51;133 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. As expected, the CA precursor (p25) of NL4-3 PRI54V+V82A was incompletely cleaved (64% cleavage) whereas the p25 of WT NL4-3 was cleaved to completion (Figure 7A). 2007 PloS one Result HIV V82A 52 56 Capsid;PR 17;45 19;47 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. As expected, the SP1/A1V mutant was resistant to bevirimat treatment but fully sensitive to 3TC (Figure 3). 2007 PloS one Result HIV A1V 21 24 SP1 17 20 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Comparison of NL4-3 and SP1/A1V kinetics by area-under-the curve analysis showed SP1/A1V to have 90% the area-under-the curve of NL4-3 for viral RNA, 74% for p24, and 79-99.9% for the parameters of thymocyte depletion shown in Figure 5B. 2007 PloS one Result HIV A1V;A1V 28;85 31;88 p24;SP1;SP1 158;24;81 161;27;84 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. For all nine mice, there was a mean of 44% WT and 56% A1V clones. 2007 PloS one Result HIV A1V 54 57 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Further support for the lack of impaired replication capacity of the SP1/A1V mutant was provided by virus competitions performed by coinfecting Thy/Liv implants with a mixture of equivalent infectious units (500 50% tissue-culture infectious doses each) of WT NL4-3 and SP1/A1V and collecting them 21 or 28 days after coinoculation. 2007 PloS one Result HIV A1V;A1V 73;274 76;277 SP1;SP1 69;270 72;273 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. In addition, there was no evidence of reversion to the WT alanine in SP1/A1V-infected implants at day 28. 2007 PloS one Result HIV A1V 73 76 SP1 69 72 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. In mixing experiments, one genome had to be present at 10-20% of the total for the minor species to be detected as a peak (the A-to-V substitution in SP1 is conferred by a C-to-T mutation at nucleotide 1880) in the sequencing chromatogram. 2007 PloS one Result HIV C1880T 172 206 SP1 150 153 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Interestingly, p25 cleavage of NL4-3 PRI54V+V82A was even more impaired in the presence of 20 microM bevirimat (29% cleavage). 2007 PloS one Result HIV V82A 44 48 PR 37 39 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. recently reported more rapid cleavage of CA-SP1 as a possible mechanism for resistance of SP1/A1V in an in vitro particle assembly system. 2007 PloS one Result HIV A1V 94 97 SP1;SP1;Capsid 44;90;41 47;93;43 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. that cleavage of the CA precusor (p25) to mature CA is significantly perturbed in bevirimat-resistant HIV-1 NL4-3 SP1/A1V, it is possible that this CA-SP1 cleavage site mutation could still affect replication capacity as a result of more subtle defects in CA maturation. 2007 PloS one Result HIV A1V 118 121 SP1;SP1;Capsid;Capsid;Capsid;Capsid 114;151;21;49;148;256 117;154;23;51;150;258 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The A1V Substitution in SP1 Does Not Affect HIV-1 Replication Capacity in the SCID-hu Thy/Liv Mouse Model. 2007 PloS one Result HIV A1V 4 7 SP1 24 27 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The clonal analysis showed 8-23% A1V sequences for these three implants, and the percentages for the other implants were in agreement with the relative proportions of the genomes in the chromatograms. 2007 PloS one Result HIV A1V 33 36 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The mean IC50 for NL4-3 PRI54V+V82A was 0.010+-0.0032 nM (n = 7; range: 0.0031-0.024), which was 140 times lower than for WT NL4-3 (1.4+-0.47 nM; range: 0.18-3.0). 2007 PloS one Result HIV V82A 31 35 PR 24 26 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The more rapid processing of CA-SP1 in the SP1/A1V mutant was confirmed in pulse-chase experiments by Adamson et al., who also showed the extent of CA-SP1 processing does not correlate with bevirimat resistance. 2007 PloS one Result HIV A1V 47 50 SP1;SP1;SP1;Capsid;Capsid 32;43;151;29;148 35;46;154;31;150 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. To determine whether bevirimat resistance might confer a fitness disadvantage to the virus in the SCID-hu Thy/Liv mouse model, we compared the replication capacity of SP1/A1V to WT NL4-3 in mice at weekly intervals after inoculation and found no evidence for impaired replication capacity of the SP1/A1V mutant (Figure 5). 2007 PloS one Result HIV A1V;A1V 171;300 174;303 SP1;SP1 167;296 170;299 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. We anticipated that this might render NL4-3 PRI54V+V82A hypersensitive to bevirimat compared to WT NL4-3, and this was shown to be the case in PHA-activated PBMCs (Figure 8). 2007 PloS one Result HIV V82A 51 55 PR 44 46 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. We reasoned that this might synergize with bevirimat activity, so we treated WT- and protease-mutant (PRI54V+V82A)-transfected 293T cells with bevirimat, and subjected supernatant virions to Western blot analysis of p25 cleavage. 2007 PloS one Result HIV V82A 109 113 PR;PR 85;102 93;104 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. We surmised that the three coinfected samples with only the A1V genome seen in the chromatogram might have WT genome below the level of detection, so we performed colony sequencing to obtain more precise percentages. 2007 PloS one Result HIV A1V 60 63 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Accordingly, we compared the AZT susceptibility of HIV-1 containing M184V and TAMs (M41L and T215Y) (NL/2AZT + 184) and HIV-1 containing M184V, TAMs, and N348I (NL/2AZT + 184 + 348). 2007 PLoS medicine Result HIV M184V;M184V;M41L;N348I;T215Y 68;137;84;154;93 73;142;89;159;98 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Although N348I did not appear to confer 3TC resistance by itself, when combined with M41L and T215Y (NL/2AZT + 348), it conferred a 3.3-fold and 1.8-fold decrease in 3TC susceptibility compared to the WT (p = 0.005, n = 5) and NL/2AZT (p = 0.008, n = 5) viruses, respectively (Table 4). 2007 PLoS medicine Result HIV M41L;N348I;T215Y 85;9;94 89;14;99 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Appearance of N348I Is Associated with a Concomitant Increase in Viral Load at Least Equivalent to That Seen with TAMs. 2007 PLoS medicine Result HIV N348I 14 19 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. As expected, M184V conferred high-level resistance to 3TC. 2007 PLoS medicine Result HIV M184V 13 18 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Association of N348I with Known RT Drug Resistance Mutations. 2007 PLoS medicine Result HIV N348I 15 20 RT 32 34 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Association of N348I with Specific Drug Treatment. 2007 PLoS medicine Result HIV N348I 15 20 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Because M184V appears with N348I and TAMs during virological failure (Figure 2), it is possible that N348I might be involved in facilitating dual AZT/3TC resistance in viruses that harbour both TAMs and M184V. 2007 PLoS medicine Result HIV M184V;M184V;N348I;N348I 8;203;27;101 13;208;32;106 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Because N348I is highly associated with TAMs (Figure 1), we also introduced N348I into molecular clones that contained M41L and T215Y (NL/2AZT + 348) or M41L, L210W, and T215Y (HX/3AZT + 348) and assayed for AZT susceptibility (Table 4). 2007 PLoS medicine Result HIV L210W;M41L;M41L;N348I;N348I;T215Y;T215Y 159;119;153;8;76;128;170 164;123;157;13;81;133;175 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Biochemical Mechanisms of AZT Resistance by Recombinant HIV-1 RT Containing N348I. 2007 PLoS medicine Result HIV N348I 76 81 RT 62 64 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. By contrast, on the RNA/DNA T/P, the 3AZT + N348I enzyme synthesised greater amounts of full-length DNA product than any of the other enzymes (Figure 3B). 2007 PLoS medicine Result HIV N348I 44 49 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Figure 3A shows that in the presence of 3 mM ATP, the 3AZT and 3AZT + N348I RTs synthesised significantly greater amounts of full-length DNA on the DNA/DNA T/P than either the WT or N348I enzymes. 2007 PLoS medicine Result HIV N348I;N348I 70;182 75;187 RT 76 79 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Furthermore, N348I also conferred EFV and NVP resistance at the enzyme level (Table 6). 2007 PLoS medicine Result HIV N348I 13 18 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, because N348I was not polymorphic and was also the most prevalent mutation in the RT connection domain, we concentrated on characterising its role in RTI drug resistance. 2007 PLoS medicine Result HIV N348I 17 22 RT;RT 159;91 162;93 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, combined treatment with AZT and NVP was associated with a 2.62-fold increased risk in the emergence of N348I compared with treatment regimens containing neither drug (Table 2). 2007 PLoS medicine Result HIV N348I 112 117 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, no significant differences were noted between the 3AZT and 3AZT+N348I enzymes (Figure 3A). 2007 PLoS medicine Result HIV N348I 73 78 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, on the RNA/DNA T/P, the 3AZT + N348I enzyme exhibited a greater capacity to excise AZT-MP than the 3AZT enzyme (Figure 4B). 2007 PLoS medicine Result HIV N348I 40 45 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, the impact of N348I on enhancing 3TC resistance in the context of M184V in either the absence or presence of the TAM combination M41L and T215Y could not be assessed as the 3TC IC50 values were beyond the detectable limits of our assay (Table 4). 2007 PLoS medicine Result HIV M184V;M41L;N348I;T215Y 75;138;23;147 80;142;28;152 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In comparison, mutations such as K65R, K70E, L74V, Q151M, and M184V increase the selectivity of RT for incorporation of natural deoxynucleoside triphosphate substrate versus the NRTI-triphosphate. 2007 PLoS medicine Result HIV K65R;K70E;L74V;M184V;Q151M 33;39;45;62;51 37;43;49;67;56 NRTI;RT 178;96 182;98 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In contrast, there was a negative association with N348I and treatment initiation taking place between 2000 and 2003 (OR 0.58, 95% CI 0.35-0.98) or between 2003 and 2005 (OR 0.27, 95% CI 0.10-0.78) relative to patients starting before 2000, perhaps due to the fact that prescription of combination therapy with AZT and NVP has been less frequent after the year 2000. 2007 PLoS medicine Result HIV N348I 51 56 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In general, N348I appeared at the same time as M184V/I and before the appearance of TAMs (Figure 2). 2007 PLoS medicine Result HIV M184I;M184V;N348I 47;47;12 54;54;17 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In order to determine whether N348I appears early in drug therapy and its pattern of emergence with respect to key drug resistance mutations, we performed an analysis on samples from a subset of patients in the Centre's database who had neither N348I nor other IAS-USA-resistance mutations present at baseline and for whom complete treatment history and viral data were known. 2007 PLoS medicine Result HIV N348I;N348I 30;245 35;250 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. M184V suppresses phenotypic resistance conferred by TAMs, although the effect decreases with an increase in the number of TAMs. 2007 PLoS medicine Result HIV M184V 0 5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Moreover, the appearance of N348I was observed during virological failure (viral loads 283-591,000 copies/ml, median 3,600). 2007 PLoS medicine Result HIV N348I 28 33 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I also potentiated NVP resistance conferred by K103N, although we could not determine the exact level of enhancement as the IC50 value was greater than what could be measured in our assay. 2007 PLoS medicine Result HIV K103N;N348I 51;0 56;5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I also usually appeared at the same time as key NNRTI resistance mutations (Figure 2). 2007 PLoS medicine Result HIV N348I 0 5 NNRTI 52 57 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I Confers Decreased Susceptibility to NNRTIs. 2007 PLoS medicine Result HIV N348I 0 5 NNRTI 42 48 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I Confers Reduced Susceptibility to AZT in a WT Backbone and When Combined with TAMs. 2007 PLoS medicine Result HIV N348I 0 5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I Decreases 3TC Susceptibility in the Context of TAMs. 2007 PLoS medicine Result HIV N348I 0 5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I Does Not Counteract Antagonism between M184V and TAMs. 2007 PLoS medicine Result HIV M184V;N348I 45;0 50;5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I Is Prevalent in Patients after Antiretroviral Therapy. 2007 PLoS medicine Result HIV N348I 0 5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I was highly associated with several key drug resistance mutations, including M184V/I (p = 6.6 x 10-45) the TAMs M41L (p = 1.8 x 10-14), D67N (p = 7.7 x 10-10), K70R (p = 1.4 x 10-10), T215Y/F (p = 6.0 x 10-21), K219Q/E (p = 8.0 x 10-4), and L210W (p = 0.002), and the NNRTI resistance mutations K103N (p = 1.1 x 10-19), V108l (p = 8.4 x 10-13), Y181C/I (p = 4.7 x 10-13) and G190A/S (p = 8.0 x 10-9) (Figure 1). 2007 PLoS medicine Result HIV D67N;G190A;G190S;K103N;K219E;K219Q;K70R;L210W;M184I;M184V;M41L;T215F;T215Y;Y181C;Y181I;N348I 141;380;380;300;216;216;165;246;82;82;117;189;189;350;350;0 145;387;387;305;223;223;169;251;89;89;121;196;196;357;357;5 NNRTI 273 278 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I was ranked as the ninth most prevalent mutation of a total of 39 RT codons evaluated and was more common than several "key" RTI mutations that are used in genotypic resistance analyses; i.e. 2007 PLoS medicine Result HIV N348I 0 5 RT;RT 130;71 133;73 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I, a mutation located in the connection domain of the RT, increased in prevalence from below 1% in samples from untreated individuals to greater than 12% in the discovery test and independent validation subsets of samples from treated individuals (p = 7.7 x 10-12) (Table 1). 2007 PLoS medicine Result HIV N348I 0 5 RT 58 60 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Nevertheless, any possible potentiating effect of N348I on 3TC resistance is unlikely to be clinically relevant given the high level of resistance conferred by M184V alone. 2007 PLoS medicine Result HIV M184V;N348I 160;50 165;55 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Notably, N348I was the first mutation that was observed in two patients (patients 5 and 16, with viral loads of 1,120 and 591,000 copies/ml, respectively) indicating an association with virological failure. 2007 PLoS medicine Result HIV N348I 9 14 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Notably, when N348I was combined with K103N, we observed a significant potentiation of EFV resistance by N348I (7.5-fold) (p = 0.005, n = 5), resulting in HIV-1 that was highly resistant to EFV (226-fold) (Table 5). 2007 PLoS medicine Result HIV K103N;N348I;N348I 38;14;105 43;19;110 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Of the 31 patients fitting these criteria, we observed that N348I tended to appear in plasma virus relatively early after initiation of antiretroviral therapy. 2007 PLoS medicine Result HIV N348I 60 65 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Other variables associated with increased risk of emergence of N348I following multivariate analysis included increased adherence and physician's experience. 2007 PLoS medicine Result HIV N348I 63 68 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Our analysis demonstrated that the appearance of N348I was associated with a significant median increase in pVL of 0.23 log10 copies/ml (p < 0.001) and that this increase was at least as large as the DeltapVL associated with each of the individual TAMs: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E (Table 3). 2007 PLoS medicine Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;N348I;T215F;T215Y 260;292;292;266;272;254;49;279;279 264;299;299;270;277;258;54;286;286 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Our data show that each of the four recombinant enzymes (WT, N348I, 3AZT, and 3AZT + N348I) was equally sensitive to inhibition by AZT-TP (Table 6), suggesting that N348I does not confer AZT resistance by a discrimination phenotype. 2007 PLoS medicine Result HIV N348I;N348I;N348I 61;85;165 66;90;170 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Pattern of Emergence of N348I Early in Drug Therapy. 2007 PLoS medicine Result HIV N348I 24 29 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Remarkably, viruses harbouring N348I conferred significant decrease in NVP (7.4-fold) (p = 0.005, n = 5) and EFV (2.5-fold) (p = 0.005, n = 5) susceptibilities (Table 5). 2007 PLoS medicine Result HIV N348I 31 36 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Similar to previous studies, K103N conferred resistance to both NVP (96-fold) and EFV (30-fold) (Table 5). 2007 PLoS medicine Result HIV K103N 29 34 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Since N348I is also highly associated with key mutations that confer NNRTI resistance (Figures 1 and 2), we investigated whether N348I could decrease susceptibility to NVP and EFV. 2007 PLoS medicine Result HIV N348I;N348I 6;129 11;134 NNRTI 69 74 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Taken together, these data demonstrate that N348I, alone and in combination with TAMs, confers AZT resistance. 2007 PLoS medicine Result HIV N348I 44 49 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Taken together, these data suggest that the N348I mutation augments the AZT excision phenotype on an RNA/DNA T/P but not on a DNA/DNA T/P. 2007 PLoS medicine Result HIV N348I 44 49 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The 3AZT and 3AZT + N348I RT were more efficient at excising AZT-MP and rescuing DNA synthesis than either the WT or N348I enzymes on a DNA/DNA T/P, but no significant differences were noted between the 3AZT and 3AZT/N348I enzymes (Figure 4A). 2007 PLoS medicine Result HIV N348I;N348I;N348I 20;117;217 25;122;222 RT 26 28 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The association of N348I with several baseline predictor variables was analysed. 2007 PLoS medicine Result HIV N348I 19 24 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The association of predictor variables with N348I was analysed by multivariate logistic regression analysis. 2007 PLoS medicine Result HIV N348I 44 49 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The data did not demonstrate a significant increase in the AZT IC50 for NL/2AZT + 184 + 348 compared with NL/2AZT + 184 (1.3-fold, p > 0.2, n = 3) (Table 4), suggesting that N348I does not counteract the antagonistic effects of M184V on phenotypic AZT resistance. 2007 PLoS medicine Result HIV M184V;N348I 228;174 233;179 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The impact of N348I on AZT susceptibility was examined by introducing this mutation by site-directed mutagenesis into the molecular clones HXB-2 (HX/348) and NL4.3 (NL/348) in order to evaluate the effect of N348I in two genetically distinct WT backbones. 2007 PLoS medicine Result HIV N348I;N348I 14;208 19;213 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. These data are consistent with a previous report demonstrating that TAMs confer decreased susceptibility to 3TC and indicate that N348I further potentiates 3TC resistance in the context of TAMs. 2007 PLoS medicine Result HIV N348I 130 135 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. These data clearly demonstrate that N348I not only confers AZT resistance but also decreases susceptibility to NNRTIs. 2007 PLoS medicine Result HIV N348I 36 41 NNRTI 111 117 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. These data demonstrate that treatment with AZT compared with treatment that did not consist of either AZT or NVP was associated with an increased risk for N348I, while there was no increased risk for N348I with NVP treatment compared with treatment with neither AZT nor NVP (Table 2). 2007 PLoS medicine Result HIV N348I;N348I 155;200 160;205 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. These data indicate that the appearance of N348I is associated with an increase in viral load that is at least as large as that observed with any of the IAS-USA-defined TAMs. 2007 PLoS medicine Result HIV N348I 43 48 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. This analysis showed that the N348I mutation, alone and in combination with 3AZT, significantly decreased RNase H cleavage activity; and in particular, decreased formation of a secondary cleavage product that reduced the RNA template to 17 nucleotides (the corresponding RNA/DNA duplex length is reduced to ten nucleotides) (Figure 4C). 2007 PLoS medicine Result HIV N348I 30 35 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. To define the biochemical mechanism by which the N348I mutation in HIV-1 RT confers resistance to AZT, we designed and performed independent experiments that assessed whether N348I, alone or in combination with M41L, L210W, and T215Y (3AZT), conferred AZT resistance by a discrimination or excision phenotype. 2007 PLoS medicine Result HIV L210W;M41L;N348I;N348I;T215Y 217;211;49;175;228 222;215;54;180;233 RT 73 75 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. To determine the potential in vivo significance of N348I, we examined whether the appearance of N348I was associated with an increase in viral load and compared this with the changes in viral load associated with each of the other TAMs (Table 3). 2007 PLoS medicine Result HIV N348I;N348I 51;96 56;101 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. To determine whether N348I was associated with the presence of other IAS-USA-defined RTI resistance mutations, we analysed the last on-therapy sample from 161 patients with N348I compared with 3,408 without N348I. 2007 PLoS medicine Result HIV N348I;N348I;N348I 21;173;207 26;178;212 RT 85 88 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. To further determine the role of N348I in the AZT excision phenotype, we next evaluated the ability of the WT or mutant RT to excise AZT-MP from the 3' terminus of the primer and to rescue DNA synthesis, as described previously. 2007 PLoS medicine Result HIV N348I 33 38 RT 120 122 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. While all TAMs were significantly associated with N348I, there was a stronger association with mutations at codons 41, 67, 70, and 215 that emerge early in drug therapy compared with mutations at codons 210 and 219 that tend to appear late in therapy. 2007 PLoS medicine Result HIV N348I 50 55 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. Four mutations were necessary to confer high resistance to the virus: K211I, I224T, S345T and E350K. 2008 Nucleic acids research Result HIV E350K;I224T;K211I;S345T 94;77;70;84 99;82;75;89 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. Furthermore, the activity of mt3 is reduced to ~38% of WT activity, whereas the additional mutation I224T of mt4 helps this enzyme to regain activity (80% of WT). 2008 Nucleic acids research Result HIV I224T 100 105 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. Our results indicate that the D24A mutation of the WT* does not interfere with polymerization activities. 2008 Nucleic acids research Result HIV D24A 30 34 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. The KD-values obtained show that there is no significant difference in substrate binding affinities of WT and mutant enzymes, implying that neither the D24A mutation nor the AZT-resistance mutations influence substrate binding. 2008 Nucleic acids research Result HIV D24A 152 156 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. This data indicates that the additional I224T change of mt4 is not important for the AZT-resistance mechanism but is necessary to improve the polymerization efficiency. 2008 Nucleic acids research Result HIV I224T 40 45 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. Thus, we decided to analyze a triple mutant PR-RT lacking the I224T mutation [mt3; (D24A), K211I, S345T and E350K] as well as the quadruple mutant harboring I224T [mt4; (D24A), K211I, I224T, S345T and E350K]. 2008 Nucleic acids research Result HIV D24A;D24A;E350K;E350K;I224T;I224T;I224T;K211I;K211I;S345T;S345T 84;170;108;201;62;157;184;91;177;98;191 88;174;113;206;67;162;189;96;182;103;196 PR;RT 44;47 46;49 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. To avoid autoprocessing of the PR domain, the enzymes also contained a D24A amino acid exchange in the active site of the PR. 2008 Nucleic acids research Result HIV D24A 71 75 PR;PR 31;122 33;124 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. In addition, when the T26S mutant PR was used, replacing the wt PR, we were able to obtain equivalent or higher (3 fold) titers than those obtained with the wt PR. 2007 Retrovirology Result HIV T26S 22 26 PR;PR;PR 34;64;160 36;66;162 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. In searching the literature, we chose a PR mutant with an altered active site in which Asp-Thr-Gly was changed to Asp-Ser-Gly (T26S). 2007 Retrovirology Result HIV T26S 127 131 Asp;Asp;PR 87;114;40 90;117;42 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. In this study 293T cells were transfected with the 7 plasmid system, in which the lentiviral GFP vector, Rev, Tat, VSV-G, Gag, and Vpr-RT/IN DNA amounts remained constant, while the concentrations of either the wt protease (Vpr-wt PR, shown in blue) or mutant protease (Vpr-T26S PR, shown in red) expression plasmids varied. 2007 Retrovirology Result HIV T26S 274 278 PR;PR;Rev;Vpr;Vpr;Vpr;Tat;Gag;IN;PR;PR;RT 214;260;105;131;224;270;110;122;138;231;279;135 222;268;108;134;227;273;113;125;140;233;281;137 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. The T26S mutation was included in the construction of the PR expression vector in which PR was fused to Vpr, leaving only 15 bases before PR for protease processing. 2007 Retrovirology Result HIV T26S 4 8 PR;Vpr;PR;PR;PR 145;104;58;88;138 153;107;60;90;140 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. These titers were obtained after optimizing transfections for variations in total DNA concentration and for molar differences in plasmids used to generate virus for the 6 (Gag-PR and Vpr-RT/IN-Vif) and 7 (Gag, Vpr-T26S PR, and Vpr-RT/IN-Vif) plasmid systems. 2007 Retrovirology Result HIV T26S 214 218 Vif;Vif;Vpr;Vpr;Vpr;Gag;Gag;IN;IN;PR;PR;RT;RT 193;237;183;210;227;172;205;190;234;176;219;187;231 196;240;186;213;230;175;208;192;236;178;221;189;233 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. We consequently continued to optimize DNA concentrations further improving viral titers produced with the 7 plasmid system, using the T26S mutant PR in place of the wt PR. 2007 Retrovirology Result HIV T26S 134 138 PR;PR 146;168 148;170 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. A protocol was first designed and tested for the specific amplification of minority L90M mutants starting from PCR products generated using generic gag-pro nested PCR (see material and methods). 2008 Retrovirology Result HIV L90M 84 88 Gag 148 151 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Alternatively, evidence for a single mutation event leading to both the early and the late L90M mutation was seen for two patients (p >= 0.95; patients 4334, 1124) while the phylogenetic evidence was inconclusive for the remaining eight patients (p: >0.05 to <0.95; patients 597, 1329, 7071, 1834, 1527, 1391, 2091, 1134). 2008 Retrovirology Result HIV L90M 91 95 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. and the later dominant L90M populations. 2008 Retrovirology Result HIV L90M 23 27 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Bayesian analysis for monophyletic origin of L90M carrying variants. 2008 Retrovirology Result HIV L90M 45 49 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. coli plasmids and the presence of the L90M mutation determined using the L90M specific primers. 2008 Retrovirology Result HIV L90M;L90M 38;73 42;77 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. For nine patients only a single time point showed the presence of low-frequency L90M mutants. 2008 Retrovirology Result HIV L90M 80 84 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Generic gag-pol amplification products from plasma samples available from earlier time points (negative for L90M by direct PCR population sequencing) were then tested using the L90M specific primers. 2008 Retrovirology Result HIV L90M;L90M 108;177 112;181 GagPol 8 15 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. In order to investigate whether the two or more sequences carrying the L90M mutation (the early minority and the later dominant variants) were originally derived from a single virus within each patient, we investigated the probability that the L90M associated sequences formed a monophyletic clade with respect to sequences lacking the L90M mutation within each patient cluster. 2008 Retrovirology Result HIV L90M;L90M;L90M 71;244;336 75;248;340 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. In order to measure the specificity of our L90M targeting PCR primer we first tested two plasmids (pAKL90 and pAK90M) encoding the w.t. 2008 Retrovirology Result HIV L90M 43 47 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Intermediate time points were available for another 6 patients and the generic gag-pro and L90M specific PCR products, when generated from these samples, were also directly sequenced. 2008 Retrovirology Result HIV L90M 91 95 Gag 79 82 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. L90 and mutant L90M codons respectively. 2008 Retrovirology Result HIV L90M 15 19 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Our analysis indicated that the L90M mutations evolved on more than one occasion in at least 5 patients (p <= 0.05; patients 1174, 1317, 1125, 6501, 608). 2008 Retrovirology Result HIV L90M 32 36 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. PCR primers were designed and tested to specifically amplify variants carrying the protease drug resistance mutation L90M present at low frequencies within quasispecies dominated by wild type viruses. 2008 Retrovirology Result HIV L90M 117 121 PR 83 91 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Relative to other L90M targeting primers tested the deletion of the 4th base and mismatching of the 5th base significantly reduced background annealing to the w.t. 2008 Retrovirology Result HIV L90M 18 22 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Selective amplification of variant carrying L90M mutation. 2008 Retrovirology Result HIV L90M 44 48 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Sequencing confirmed, through the detection of all 15 internal mutations distinguishing pAK90M from pAKL90, that the L90M specific primers had specifically amplified the L90M variant at the highest dilutions. 2008 Retrovirology Result HIV L90M;L90M 117;170 121;174 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The early presence of low frequency L90M variants was detected in fifteen of the forty-five patients. 2008 Retrovirology Result HIV L90M 36 40 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The early time point amplicons generated using the L90M specific primer were also directly sequenced to determine the consensus sequence of these minority L90M populations. 2008 Retrovirology Result HIV L90M;L90M 51;155 55;159 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The L90M mutation being located near the extremity of the protease gene also allowed linkage of early L90M mutations with other upstream protease polymorphisms. 2008 Retrovirology Result HIV L90M;L90M 4;102 8;106 PR;PR 58;137 66;145 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The L90M specific primer AK90m was designed with its three 3' end nucleotides complementary to the L90M methionine codon (ATG). 2008 Retrovirology Result HIV L90M;L90M 4;99 8;103 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The later time point generic gag-pro sequences invariably confirmed the dominance of the L90M mutation which was detectable by direct population sequencing while the earlier time point only showed w.t. 2008 Retrovirology Result HIV L90M 89 93 Gag 29 32 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The presence of L90M DNA could still be detected after a 1000 fold dilution while the L90 DNA target generated only a shorter non-specific fragment at the highest L90M dilutions. 2008 Retrovirology Result HIV L90M;L90M 16;163 20;167 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The sequence of the L90M plasmid subclones were also compared to those derived by sequencing the L90M specific amplicons derived from the generic gag-pol PCR. 2008 Retrovirology Result HIV L90M;L90M 20;97 24;101 GagPol 146 153 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The sequence polymorphisms distinguishing the L90M specific amplicons from their respective majority population sequences were similar to those detected in the L90M positive plasmid subclones (data not shown). 2008 Retrovirology Result HIV L90M;L90M 46;160 50;164 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. These PCR product log dilutions were then tested using the L90M specific primer pair (AKG3 and AK90m). 2008 Retrovirology Result HIV L90M 59 63 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. These plasmids were purified and the presence of the L90M mutations confirmed by plasmid insert sequencing. 2008 Retrovirology Result HIV L90M 53 57 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. These results further support the specificity of detection of minority L90M variants using our allele specific PCR protocol. 2008 Retrovirology Result HIV L90M 71 75 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. To analyze the early evolution of L90M longitudinally collected plasma samples from 45 patients who developed L90M (as detected by direct PCR population sequencing) were obtained. 2008 Retrovirology Result HIV L90M;L90M 34;110 38;114 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. To confirm that the amplicons generated from the highest pAK90M PCR DNA dilutions (1:200 and 1:1000) were indeed derived from the minority L90M variant they were purified and directly sequenced. 2008 Retrovirology Result HIV L90M 139 143 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. To further evaluate the discriminatory capability of the L90M specific primer AK90m and more closely mimic conditions using clinical samples serial dilutions of the L90M PCR products were mixed with a constant amount of L90 PCR products. 2008 Retrovirology Result HIV L90M;L90M 57;165 61;169 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. To further substantiate the specificity of our L90M specific amplifications we analyzed the second PCR round generic gag-pro PCR products from two plasma samples in which the L90M variants were detected only using L90M specific primers. 2008 Retrovirology Result HIV L90M;L90M;L90M 47;175;214 51;179;218 Gag 117 120 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Two colony PCRs from 608 and one from 1391 were L90M positive. 2008 Retrovirology Result HIV L90M 48 52 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Up to 104 fold dilutions of the L90M generic gag-pro PCR products could be amplified while none of the L90 generic gag-pro PCR products was amplified (Fig 1B). 2008 Retrovirology Result HIV L90M 32 36 Gag;Gag 45;115 48;118 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. We targeted the protease L90M mutation as a frequently selected primary drug resistant mutation providing measurable levels of resistance to all currently approved protease inhibitors. 2008 Retrovirology Result HIV L90M 25 29 PR;PR 16;164 24;172 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. white) from each subcloning were replica plated and the presence of L90M in their inserts tested by colony PCR (see materials and methods). 2008 Retrovirology Result HIV L90M 68 72 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Again, we found that the introduction of the K43E change in the M41L+T215Y+E40F virus did not lead to a significant change in Zidovudine resistance (Table 3), indicating that the effect of K43E (in the presence of E40F) is compensatory on the viral RC. 2008 Retrovirology Result HIV E40F;E40F;K43E;K43E;M41L;T215Y 75;214;45;189;64;69 79;218;49;193;68;74 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Also the K43E change was found in 5.3% of samples with other resistance mutations but only 0.1% of samples with no predicted resistance (OR = 52, p < 0.0001). 2008 Retrovirology Result HIV K43E 9 13 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Association between E40F and K43E. 2008 Retrovirology Result HIV E40F;K43E 20;29 24;33 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Association of the E40F and K43E changes with NRTI-treatment and resistance. 2008 Retrovirology Result HIV E40F;K43E 19;28 23;32 NRTI 46 50 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Both mutations are co-varying with TAM-1 pathway mutations and therefore we determined the effect of the E40F and K43E changes on thymidine analogue resistance (Zidovudine) in a set of clinically relevant reference viruses (Table 3). 2008 Retrovirology Result HIV E40F;K43E 105;114 109;118 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Changing the mutant K43E codon to the wild type codon in the Pat A virus clone (Pat A-WT43) resulted in a reduction of viral RC. 2008 Retrovirology Result HIV K43E 20 24 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. clearly indicating that the K43E change has a compensatory role in this patient-derived virus clone. 2008 Retrovirology Result HIV K43E 28 32 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Effect of E40F change on RC. 2008 Retrovirology Result HIV E40F 10 14 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Effect of K43E change on RC. 2008 Retrovirology Result HIV K43E 10 14 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Furthermore, a virus clone containing the N-terminal part of RT of a patient-derived virus isolate (Pat A) containing both E40F and K43E changes was made. 2008 Retrovirology Result HIV E40F;K43E 123;132 127;136 RT 61 63 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. HIV-1 strains harbouring E40F and/or K43E showed the strongest association with all TAM-1 pathway mutations (M41L, L210W and T215Y). 2008 Retrovirology Result HIV E40F;K43E;L210W;M41L;T215Y 25;37;115;109;125 29;41;120;113;130 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. In addition, we determined its effect in the wild type reference virus or the recombinant virus M41L+T215Y. 2008 Retrovirology Result HIV M41L;T215Y 96;101 100;106 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. In one out of four experiments the presence of the K43E change could lead to the acquisition of a change at position 215 (T-to-I, Table 4). 2008 Retrovirology Result HIV K43E 51 55 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Indeed, replication competition experiments showed that the addition of K43E resulted in an increase in viral RC. 2008 Retrovirology Result HIV K43E 72 76 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Indeed, the introduction of the E40F change in the background of M41L and T215Y resulted in a gradual reduction of the M41L+T215Y+E40F, indicating that the E40F change results in a clear decrease in RC. 2008 Retrovirology Result HIV E40F;E40F;E40F;M41L;M41L;T215Y;T215Y 32;130;156;65;119;74;124 36;134;160;69;123;79;129 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Interestingly, the E40F substitution change showed the highest association with K43E (OR of 38.2 and phi-value of 0.287, p < 0.0001). 2008 Retrovirology Result HIV E40F;K43E 19;80 23;84 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Introducing the wild type amino acid at codon 43 in the Pat A-virus clone (Pat A-WT43) could lead to a change of the E40F amino acid change (E40F/L) in one out of four experiments. 2008 Retrovirology Result HIV E40F;E40F;E40L 117;141;141 121;147;147 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Introduction of the K43E change did not lead to a change in IC50 for Zidovudine in the viruses that were tested. 2008 Retrovirology Result HIV K43E 20 24 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Likewise, K43Q (resistant virus: 3.3%; OR: 23, p < 0.0001) and K43N (resistant virus: 1.8%; OR: 11; p < 0.0001) were found predominantly in association with other resistance mutations. 2008 Retrovirology Result HIV K43N;K43Q 63;10 67;14 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Mutations from the TAM-2 pathway (D67N, K70R, T215F and K219Q/E) were only weakly or even negatively associated with the E40F and K43E changes, with the exception of the D67N substitution, which has also been associated with the TAM-1 pathway. 2008 Retrovirology Result HIV D67N;D67N;E40F;K219E;K219Q;K43E;K70R;T215F 34;170;121;56;56;130;40;46 38;174;125;63;63;134;44;51 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The introduction of the E40F change in the background of M41L and T215Y resulted in a 14-fold further increase in Zidovudine-resistance when compared to the M41L+T215Y double mutant. 2008 Retrovirology Result HIV E40F;M41L;M41L;T215Y;T215Y 24;57;157;66;162 28;61;161;71;167 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The K43E change was found in 84% of all E40F-containing viruses. 2008 Retrovirology Result HIV E40F;K43E 40;4 44;8 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The presence of E40F was limited to samples that contained additional (RTI) resistance-associated mutations (0.6%; Odds ratio: 363; p < 0.0001) however the frequency of E40D was not significantly different in predicted ARV-resistant and ARV-sensitive samples. 2008 Retrovirology Result HIV E40D;E40F 169;16 173;20 RT 71 74 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. These assays did not reveal any effect of the K43E change in the wild type or the M41L+T215Y background. 2008 Retrovirology Result HIV K43E;M41L;T215Y 46;82;87 50;86;92 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. This may indicate that in the absence of the positive effect of the K43E change on RC, the virus can improve its RC by removal of the E40F change. 2008 Retrovirology Result HIV E40F;K43E 134;68 138;72 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To better understand the role of the E40F and K43E substitutions we analyzed the frequencies of these substitutions in the Quest Diagnostics reference laboratory database containing more than 160,000 (RT) sequences from patients across the United States (1/1/1999-12/31/2005). 2008 Retrovirology Result HIV E40F;K43E 37;46 41;50 RT 201 203 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To determine if the K43E change has a compensatory role by increasing the viral RC, replication competition experiments were performed using a panel of site-directed mutants. 2008 Retrovirology Result HIV K43E 20 24 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To determine if the K43E change is indeed compensatory for the deleterious effect of the E40F mutation on viral RC, the additional effect of K43E in the background of M41L+T215Y+E40F was determined. 2008 Retrovirology Result HIV E40F;E40F;K43E;K43E;M41L;T215Y 89;178;20;141;167;172 93;182;24;145;171;177 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. We also noted a positive association between K43E and amino acid changes E44A, V118I, H208Y, K219N/R and V75M (data not shown; p values were highly significant at an FDR level of 0.01 in all cases). 2008 Retrovirology Result HIV E44A;H208Y;K219N;K219R;K43E;V118I;V75M 73;86;93;93;45;79;105 77;91;100;100;49;84;109 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. We determined whether the E40F change causes resistance at the cost of reducing replicative capacity by performing competition experiments. 2008 Retrovirology Result HIV E40F 26 30 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. We hypothesized that the K43E substitution could be compensatory for the E40F substitution, since these changes are highly associated with each other (Table 2). 2008 Retrovirology Result HIV E40F;K43E 73;25 77;29 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. We investigated the association of the E40F and K43E changes with each other and with the known thymidine associated mutations (M41L, D67N, K70R, L210W, T215Y/F and K219Q/E; Table 2). 2008 Retrovirology Result HIV D67N;E40F;K219E;K219Q;K43E;K70R;L210W;M41L;T215F;T215Y 134;39;165;165;48;140;146;128;153;153 138;43;172;172;52;144;151;132;160;160 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). In only one case (the A46R deletion), was any mutation detected: a primer-derived single nucleotide deletion in the intergenic region downstream of the insertion. 2008 PloS one Result HIV A46R 22 26 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). MVA-BAC clone #26 was selected for shotgun sequencing at eightfold coverage, resulting in a single contig (excluding the repeat regions), and was found to be identical to the Acambis/Bavarian Nordic strain, with the exception of a 6 bp insertion in the non-essential gene F7L . 2008 PloS one Result HIV F7L 272 275 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. A recent study has shown that the connection domain mutation G333D can increase substrate binding under steady-state conditions. 2008 The Journal of biological chemistry Result HIV G333D 61 66 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. A360V and N348I Reduce RNase H Activity and Mediate the Accumulation of Truncated Substrates:N348I-containing mutant enzymes were shown to reduce RNase H activity. 2008 The Journal of biological chemistry Result HIV N348I;N348I;A360V 10;93;0 15;98;5 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. A360V appears to compensate for this deficit, whereas N348I shows no significant effect on substrate binding in this context. 2008 The Journal of biological chemistry Result HIV N348I;A360V 54;0 59;5 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. A360V usually appeared late in therapy, on average 2.5 years after the onset of antiretroviral treatment, and typically appeared after TAMs selection. 2008 The Journal of biological chemistry Result HIV A360V 0 5 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Accumulation of Transiently Formed DNA RNA Hybrids:As a consequence of the diminished RNase H activity with A360V and N348I, medium sized fragments (e.g. 2008 The Journal of biological chemistry Result HIV A360V;N348I 108;118 113;123 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Also, the same effect is seen when comparing TAMs/A360V/N348I with TAMs/A360V/N348I/E478Q, which shows that the loss of RNase H activity enhances the rescue reaction. 2008 The Journal of biological chemistry Result HIV A360V;A360V;E478Q;N348I;N348I 50;72;84;56;78 55;77;89;61;83 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Connection Domain Mutations A360V and N348I Increase ATP-mediated Excision on DNA RNA Substrates:The combination of A360V and N348I, when present against a background of TAMs was shown to amplify resistance to AZT but not to d4T. 2008 The Journal of biological chemistry Result HIV A360V;A360V;N348I;N348I 28;116;38;126 33;121;43;131 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Effect of N348I and A360V on HIV-1 RT Processivity:Differences in substrate binding in polymerase-competent complexes are generally low, although A360V appears to correct for the modest deficiency of TAMs. 2008 The Journal of biological chemistry Result HIV A360V;A360V;N348I 20;146;10 25;151;15 Pol;RT 87;35 97;37 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Formation of the full-length product is much higher with TAMs/A360V/N348I/E478Q, which shows that the contribution to increases in rescue of DNA synthesis is in part RNase H-independent. 2008 The Journal of biological chemistry Result HIV A360V;E478Q;N348I 62;74;68 67;79;73 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Furthermore, A360V was highly correlated with various mutations considered to be part of the TAMs cluster; for example, of the samples with A360V, 35% were associated with M41L, 21% with D67N, 30% with K70R, 17% with L210W, 42% with T215Y/F, and 17% with K219Q/E. 2008 The Journal of biological chemistry Result HIV A360V;A360V;D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 13;140;187;255;255;202;217;172;233;233 18;145;191;262;262;206;222;176;240;240 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. However, marked increases in AZT-MP excision and rescue of DNA synthesis with TAMs/N348I and TAMs/A360V/N348I were observed. 2008 The Journal of biological chemistry Result HIV A360V;N348I;N348I 98;104;83 103;109;88 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. In addition, the comparison of TAMs/A360V/N348I/E478Q with TAMs/E478Q points to a strong RNase H-independent component. 2008 The Journal of biological chemistry Result HIV A360V;E478Q;N348I;E478Q 36;48;42;64 41;53;47;69 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. In contrast, less than 20% of samples with the A360T had TAMs. 2008 The Journal of biological chemistry Result HIV A360T 47 52 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. In this experiment, we compared WT RT with TAMs/A360V/N348I that showed a severe reduction in RNase H cleavage. 2008 The Journal of biological chemistry Result HIV A360V;N348I 48;54 53;59 RT 35 37 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. In Vivo Prevalence of A360V:The in vivo prevalence of mutations in the connection domain of RT was studied in a large cohort of individuals from British Columbia, Canada, as a function of exposure to antiretroviral selection pressure. 2008 The Journal of biological chemistry Result HIV A360V 22 27 RT 92 94 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Like the N348I mutation, A360V was observed in less than 1% of the untreated population (n = 15 of 1606) and increased to 8.5% after treatment (n = 205 of 2422). 2008 The Journal of biological chemistry Result HIV A360V;N348I 25;9 30;14 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. N348I Increases PPi-mediated Excision of AZT-MP:At this point, our data show that both factors (i) reduced RNase H activity and (ii) increased processivity correlate with increases in ATP-dependent excision of AZT-MP and rescue of DNA synthesis when TAMs and connection domain mutations are combined. 2008 The Journal of biological chemistry Result HIV N348I 0 5 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Other mutations (A360I and A360S) were observed only rarely. 2008 The Journal of biological chemistry Result HIV A360I;A360S 17;27 23;32 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Our data show that the N348I mutant confers increases in PPi-mediated rescue of AZT-terminated DNA synthesis when compared with WT RT and TAMs (supplemental. 2008 The Journal of biological chemistry Result HIV N348I 23 28 RT 131 133 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Overall, the efficiency of RNase H cleavage follows the order WT RT > TAMs > TAMs/A360V > TAMs/N348I > TAMs/A360V/N348I, which correlates inversely with the respective efficiencies of excision. 2008 The Journal of biological chemistry Result HIV A360V;N348I;A360V;N348I 108;114;82;95 113;119;87;100 RT 65 67 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Processive DNA synthesis is then increased in the following order: TAMs/A360V < TAMs/N348I < TAMs/A360V/N348I. 2008 The Journal of biological chemistry Result HIV A360V;N348I;A360V;N348I 98;104;72;85 103;109;77;90 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. TAMs/A360V showed a moderate 3.6-fold increase in Kd values, TAMs/N348I showed an 8.8-fold increase, and RNase H activity is hardly detectable when both mutations were combined with TAMs. 2008 The Journal of biological chemistry Result HIV A360V;N348I 5;66 10;71 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The A360V mutation appeared in over 120 TAM contexts, but the most common TAM patterns in which it appeared consisted of M41L/215Y or M41L/L210W/T215Y. 2008 The Journal of biological chemistry Result HIV L210W;M41L;T215Y;A360V;M41L 139;134;145;4;121 144;138;150;9;125 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The data show that enzymes containing TAMs/A360V and TAMs/N348I, respectively, increased full-length product formation when compared with TAMs. 2008 The Journal of biological chemistry Result HIV A360V;N348I 43;58 48;63 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The effects of A360V are by far not as pronounced as seen with N348I. 2008 The Journal of biological chemistry Result HIV A360V;N348I 15;63 20;68 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The efficiency of excision showed the following order in a time course: WT RT < TAMs < TAMs/A360V/N348I. 2008 The Journal of biological chemistry Result HIV A360V;N348I 92;98 97;103 RT 75 77 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The efficiency of rescue of DNA synthesis follows the order WT RT < TAMs < TAMs/A360V < TAMs/N348I < TAMs/A360V/N348I. 2008 The Journal of biological chemistry Result HIV A360V;N348I;A360V;N348I 106;112;80;93 111;117;85;98 RT 63 65 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The increase in prevalence at codon 360 was driven in part by a modest increase in the prevalence of a common polymorphism A360T, but predominantly by an increase in the A360V substitution. 2008 The Journal of biological chemistry Result HIV A360T;A360V 123;170 128;175 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The RT enzymes containing TAMs alone or TAMs/A360V did not show significant differences in full-length product formation. 2008 The Journal of biological chemistry Result HIV A360V 45 50 RT 4 6 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The same result was obtained with the short hybrid substrate, which helps to explain why connection domain mutations N348I and A360V do not amplify resistance to d4T (supplemental. 2008 The Journal of biological chemistry Result HIV A360V;N348I 127;117 132;122 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Thus, the subtle increases in substrate binding in the polymerase-competent mode translate into increases in processive DNA synthesis with A360V-containing enzymes. 2008 The Journal of biological chemistry Result HIV A360V 139 144 Pol 55 65 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. To address this, we introduced the RNase H-negative E478Q mutation against a background of TAMs and TAMs/A360V/N348I. 2008 The Journal of biological chemistry Result HIV A360V;N348I;E478Q 105;111;52 110;116;57 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. To test whether these effects can be seen independently of TAMs, which do not appear to improve binding and usage of PPi, we conducted the same experiment with the single mutations A360V and N348I, respectively. 2008 The Journal of biological chemistry Result HIV A360V;N348I 181;191 186;196 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Unexpectedly, N348I-containing enzymes can likewise increase processive DNA synthesis, although these enzymes do not appear to increase nucleic acid binding in this context. 2008 The Journal of biological chemistry Result HIV N348I 14 19 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. When comparing TAMs with TAMs/E478Q, we observed increases in ATP-dependent rescue of AZT-terminated DNA synthesis. 2008 The Journal of biological chemistry Result HIV E478Q 30 35 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. A greater proportion of SD NVP-experienced women had detectable K103N at 12 months. 2008 The Journal of infectious diseases Result HIV K103N 64 69 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Analysis of samples collected at 6 and 12 months was limited to women who had detectable K103N at the prior study visit. 2008 The Journal of infectious diseases Result HIV K103N 89 94 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Fifteen women who had K103N detected at 6 months had a 12-month sample available for analysis. 2008 The Journal of infectious diseases Result HIV K103N 22 27 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Forty women who had K103N detected at 6 weeks had a 6-month sample available for analysis. 2008 The Journal of infectious diseases Result HIV K103N 20 25 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Her baseline (pre-NVP) sample in the RP study was collected 7-8 months later; that sample had 33.5% K103N. 2008 The Journal of infectious diseases Result HIV K103N 100 105 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. In two infants, the same mutation was detected at 6 weeks and 6 months (one with V106M and one with Y181C). 2008 The Journal of infectious diseases Result HIV V106M;Y181C 81;100 86;105 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. In two samples, mutations detected with ViroSeq were not detected with LigAmp (one sample had nucleotide polymorphisms at the LigAmp oligonucleotide binding sites; one sample used an alternative codon for Y181C). 2008 The Journal of infectious diseases Result HIV Y181C 205 210 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Infant samples from 6 weeks of age were also analyzed using the LigAmp assay to detect and quantify K103N, Y181C, and G190A. 2008 The Journal of infectious diseases Result HIV G190A;K103N;Y181C 118;100;107 123;105;112 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. K103N was detected in only 3 (3.4%) of 89 women, one SD NVP-experienced woman and two SD NVP-naive women. 2008 The Journal of infectious diseases Result HIV K103N 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. One infant, who had K103N+Y181C at 6 weeks, had Y181C detected at 6 months. 2008 The Journal of infectious diseases Result HIV K103N;Y181C;Y181C 20;26;48 25;31;53 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. One SD NVP-naive woman had 1.6% K103N prior to delivery in the RP study; that woman had received an extra dose of NVP 12 days prior to delivery due to premature labor. 2008 The Journal of infectious diseases Result HIV K103N 32 37 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. The median level of K103N detected was slightly higher in the SD NVP-experienced group, however the difference was not statistically significant (Table 2). 2008 The Journal of infectious diseases Result HIV K103N 20 25 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. The mutations detected by LigAmp were present at levels less than 10% with one exception: G190A was detected at 60% in one infant. 2008 The Journal of infectious diseases Result HIV G190A 90 95 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. The other SD NVP-naive woman, who had no prior history of SD NVP exposure, had 0.7% K103N. 2008 The Journal of infectious diseases Result HIV K103N 84 89 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. There was no significant difference in the proportion of SD NVP-naive women versus SD NVP-experienced women with detectable K103N at 6 months. 2008 The Journal of infectious diseases Result HIV K103N 124 129 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Using this assay, K103N was detected in 26 (45.6%) of 57 SD NVP-naive women and 15 (45.5%) of 33 SD NVP-experienced women (Table 2). 2008 The Journal of infectious diseases Result HIV K103N 18 23 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. We also used the LigAmp assay for analysis of K103N in these samples. 2008 The Journal of infectious diseases Result HIV K103N 46 51 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. We examined persistence of K103N among women who had K103N detected at 6 weeks (Table 2). 2008 The Journal of infectious diseases Result HIV K103N;K103N 27;53 32;58 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Also, the absence of large structural changes in the saquinavir complex agrees with the rarity of the I50V mutation during resistance to saquinavir. 2008 Journal of molecular biology Result HIV I50V 102 106 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Analysis of the available structures of these flap mutants with saquinavir or darunavir showed the largest changes in PRG48V/L90M-SQV and PRI50V-DRV relative to the corresponding wild type complexes. 2008 Journal of molecular biology Result HIV L90M 125 129 PR;PR 118;138 120;140 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Hence, darunavir is likely to be a better drug for patients carrying HIV PR with the G48V mutation selected by saquinavir treatment, while saquinavir may be better for resistant HIV with the I50V mutation. 2008 Journal of molecular biology Result HIV G48V;I50V 85;191 89;195 PR 73 75 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. However, no significant reduction in inhibitor interactions was observed in the structures of PRI54V-DRV, PRI54V-SQV and PRI54M-SQV. 2008 Journal of molecular biology Result HIV I54M;I54V 123;108 127;112 PR;PR;PR 94;106;121 96;108;123 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. However, PRG48V was more susceptible to darunavir than saquinavir, in agreement with the presence of G48V in clinical isolates failing saquinavir therapy. 2008 Journal of molecular biology Result HIV G48V 101 105 PR 9 11 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. However, the crystal structure of the double mutant PRG48V/L90M with SQV (1FB7) shows that saquinavir moves to accommodate the bigger side chain of Val48, giving rise to weaker interactions than in the PR-SQV structure. 2008 Journal of molecular biology Result HIV L90M 59 63 PR;PR 52;202 54;204 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Importantly, saquinavir showed reduced inhibition and hydrogen bond interactions for mutants containing G48V and less change with PRI50V, while the opposite is seen for darunavir, in excellent agreement with the resistance data and despite the reduced activity of these mutants. 2008 Journal of molecular biology Result HIV G48V 104 108 PR 130 132 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. In summary, the I54M mutation caused larger structural changes than I54V in the flap and in the interactions with darunavir, which is consistent with the more frequent occurrence of mutation I54M compared to I54V in the treatment with amprenavir and darunavir. 2008 Journal of molecular biology Result HIV I54M;I54M;I54V;I54V 16;191;68;208 20;195;72;212 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Moreover, the flap tip has shifted towards Met54 by 0.5 A at the carbonyl O of Gly51, because there is more space due to the absence of the beta-branched methyl group of Ile in Met54. 2008 Journal of molecular biology Result HIV I54M 170 182 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. On the other hand, the G48V mutation is not considered to be resistant to darunavir, although potentially repulsive protease-inhibitor contacts were observed in the new structure of PRG48V-DRV. 2008 Journal of molecular biology Result HIV G48V;G48V 23;184 27;188 PR;PR 116;182 124;184 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. On the other hand, the mutation I54V introduces a smaller side chain, so the 80's loop has shifted towards Val54 by 0.6 A at the carbonyl O of Pro79' in only one subunit of PRI54V-DRV. 2008 Journal of molecular biology Result HIV I54V 32 36 PR 173 175 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. PRI50V was inhibited more effectively by saquinavir than by darunavir, in agreement with the presence of the I50V mutation in HIV isolates resistant to darunavir and its rarity in saquinavir treatment. 2008 Journal of molecular biology Result HIV I50V 109 113 PR 0 2 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Replacing Gly48 by Val in PRG48V is expected to disrupt the interactions with neighboring residues on the flap, and possibly alter the interactions with the inhibitor, thus destabilizing the flap and reducing the affinity for inhibitor. 2008 Journal of molecular biology Result HIV G48V 10 22 PR 26 28 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Saquinavir appeared to adapt better than darunavir to the changes caused by I54M and I54V, which is consistent with the increased prevalence of both mutations in HIV isolates showing resistance to darunavir. 2008 Journal of molecular biology Result HIV I54M;I54V 76;85 80;89 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The 80's loop shows intrinsic flexibility as described previously for atomic resolution structures of saquinavir complexes with wild type PR and mutants V82A and I84V and a 9X mutant with indinavir. 2008 Journal of molecular biology Result HIV I84V;V82A 162;153 166;157 PR 138 140 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The hydrogen bond between Gly48 and saquinavir was absent in the structure of PRG48V/L90M-SQV, consistent with the 90-fold reduced inhibition. 2008 Journal of molecular biology Result HIV L90M 85 89 PR 78 80 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The loss of hydrogen bond interactions with inhibitor in PRI50V appears to provide resistance to darunavir, and in PRG48V/L90M to provide resistance to saquinavir, as suggested in previous studies. 2008 Journal of molecular biology Result HIV L90M 122 126 PR;PR 57;115 59;117 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The role of Ile/Val50 in binding of indinavir or darunavir has been described previously. 2008 Journal of molecular biology Result HIV I50V 16 21 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. The wild type HIV-1 PR in these studies contains mutations Q7K, L33I, and L63I to diminish autoproteolysis and C67A and C95A to prevent cysteine-thiol oxidation, and showed almost identical kinetic parameters, stability and dimer dissociation as the unmutated wild type PR. 2008 Journal of molecular biology Result HIV C67A;C95A;L33I;L63I;Q7K 111;120;64;74;59 115;124;68;78;62 PR;PR 20;270 22;272 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Therefore, the mutations of flap residues Ile50 and Phe53 adversely affect the PR dimer stability, while mutations G48V and I54V/M had no significant effect on the dimer stability in this assay. 2008 Journal of molecular biology Result HIV G48V;I54M;I54V 115;124;124 119;130;130 PR 79 81 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. These structural changes and reduced protease-inhibitor interactions, including loss of a hydrogen bond, explain why G48V is a primary mutation observed in isolates that are resistant to saquinavir. 2008 Journal of molecular biology Result HIV G48V 117 121 PR 37 45 18597780 Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir. Unlike in PRI54M-DRV, the tip of the flap had no significant change in PRI54V-DRV relative to the wild type PR structure. 2008 Journal of molecular biology Result HIV I54V 73 77 PR;PR;PR 10;71;108 12;73;110 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Accordingly, the infectivity rescue observed for the VSV-G-S149A and VSV-G-S178A viruses cannot be ascribed to an overestimation due to the use of saturating doses of VSV-G-WT. 2008 Retrovirology Result HIV S149A;S178A 59;75 64;80 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. All viruses tested were thus competent for fusion with the target cell membrane and inhibition of replication observed for S109A, S149A and S178A mutants occurred at a post-fusion step, as previously proposed. 2008 Retrovirology Result HIV S109A;S149A;S178A 123;130;140 128;135;145 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Altogether these data indicate that the S178A mutation does not compromise the ability of CA to assemble in vivo. 2008 Retrovirology Result HIV S178A 40 45 Capsid 90 92 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Altogether, our data indicate that infection through the endocytic pathway restored the ability of S149A and S178A mutants to produce 2-LTR DNA. 2008 Retrovirology Result HIV S149A;S178A 99;109 104;114 LTR 136 139 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Analyzing cell free virions normalized according to RTase activity (Figure 6B), the expected ratio of Gag precursor, p41 intermediate and mature CA were observed for S149A and S178A virions as compared to WT. 2008 Retrovirology Result HIV S149A;S178A 166;176 171;181 Gag;Capsid 102;145 105;147 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. As expected, 2-LTR circles could not be amplified from cells infected with VSV-G-S109A. 2008 Retrovirology Result HIV S109A 81 86 LTR 15 18 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. As shown in Figure 5A and 5B, the presence of normal-sized mature virions was observed in preparations of WT, S149A and S178A particles. 2008 Retrovirology Result HIV S149A;S178A 110;120 115;125 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Cone shaped structures were also predominantly observed from preparations of S178A cores and more rarely from S149A samples. 2008 Retrovirology Result HIV S149A;S178A 110;77 115;82 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Consistent with infectivity assays, 2-LTR DNA was produced efficiently in cells infected with VSV-G-S149A and VSV-G-S178A. 2008 Retrovirology Result HIV S149A;S178A 100;116 105;121 LTR 38 41 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Due to the aberrant morphology of the structures purified, the S109A mutant was excluded from subsequent experiments. 2008 Retrovirology Result HIV S109A 63 68 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Finally, level of first strand transfer DNA was significantly decreased and full-length minus strand DNA synthesis was almost abolished in cells infected with S109A viruses indicating that early reverse transcription was drastically reduced in these cells. 2008 Retrovirology Result HIV S109A 159 164 RT 195 216 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Finally, replication of VSV-G-S149A and VSV-G-S178A was abolished when MAGIC-5B cells were maintained in the presence of 20 muM AZT indicating that LTR-transactivation is not due to a pseudo-transduction artefact. 2008 Retrovirology Result HIV S149A;S178A 30;46 35;51 LTR 148 151 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Following VSV-G incorporation, RT efficiency was increased by 11 and 15-fold in cells infected with WT and S178A viruses respectively (Figure 3D). 2008 Retrovirology Result HIV S178A 107 112 RT 31 33 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. For testing similar effects, S109A, S149A and S178A mutants pseudotyped with VSV-G envelope were generated by co-transfection of proviral clones with a plasmid expressing VSV-G. 2008 Retrovirology Result HIV S109A;S149A;S178A 29;36;46 34;41;51 Env 83 91 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Formation of 2-LTR DNA was next investigated in cells infected with VSV-G-S149A or VSV-G-S178A viruses (figure 3E). 2008 Retrovirology Result HIV S149A;S178A 74;89 79;94 LTR 15 18 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Having demonstrated that VSV-G incorporation rescues infectivity of S149A and S178A mutant particles, we investigated the ability of these pseudotyped mutants to synthesize proviral DNA. 2008 Retrovirology Result HIV S149A;S178A 68;78 73;83 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Hence, Gag maturation is compromised by S109A mutation in CA. 2008 Retrovirology Result HIV S109A 40 45 Gag;Capsid 7;58 10;60 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Impact of S109A, S149A and S178A mutations on core recognition by TRIM family restriction factors. 2008 Retrovirology Result HIV S109A;S149A;S178A 10;17;27 15;22;32 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In cells infected with the S178A mutant, first-strand transfer, full-length minus strand and second-strand transfer DNAs copies ranged from 70 to 95% levels quantified from cells infected by WT viruses. 2008 Retrovirology Result HIV S178A 27 32 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, RT progression remained dramatically impaired in cells infected with VSV-G-S109A viruses. 2008 Retrovirology Result HIV S109A 88 93 RT 13 15 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, RT was found most drastically altered in cells infected with S149A virus, as synthesis of full-length minus strand and second-strand transfer DNAs was reduced by nearly 70% compared to control conditions. 2008 Retrovirology Result HIV S149A 74 79 RT 13 15 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, S109A particles displayed a significant decrease in size. 2008 Retrovirology Result HIV S109A 13 18 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, S109A virions presented an accumulation of unprocessed Gag and processing intermediates, including p41 and p25. 2008 Retrovirology Result HIV S109A 13 18 Gag 68 71 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, S149A and S178A mutants produced different levels of second-strand transfer DNA and were impaired in their ability to produce 2-LTR circles. 2008 Retrovirology Result HIV S149A;S178A 13;23 18;28 LTR 141 144 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, S149A particles displayed mild morphological defects characterized by irregularly shaped cores. 2008 Retrovirology Result HIV S149A 13 18 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, VSV-G-S109A viruses remained weakly infectious. 2008 Retrovirology Result HIV S109A 19 24 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In these cells, beta-galactosidase activity was observed to be dramatically enhanced when S149A or S178A particles were delivered to the cell by the endocytic pathway [Additional file 2]. 2008 Retrovirology Result HIV S149A;S178A 90;99 95;104 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In these conditions, infectivity of MLV Env-S109A and MLV Env-S149A was comparable to that of the corresponding mutants expressing HIV Env. 2008 Retrovirology Result HIV S109A;S149A 44;62 49;67 Env;Env;Env 40;58;135 43;61;138 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In vivo assembly and maturation of S109A, S149A and S178A mutant viruses. 2008 Retrovirology Result HIV S109A;S149A;S178A 35;42;52 40;47;57 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Indeed, beta-galactosidase activity generated in MAGIC-5B cells was found to be 2% vs 4.3% for MLV Env-S109A and non pseudotyped S109A viruses respectively or 6% vs 4% for MLV Env-S149A and non-pseudotyped S149A viruses respectively when compared to WT virus expressing the corresponding envelope glycoproteins. 2008 Retrovirology Result HIV S109A;S109A;S149A;S149A 103;129;180;206 108;134;185;211 Env;Env;Env 288;99;176 296;102;179 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Infectivity of S149A and S178A mutants is restored when delivered to the host cell through the endocytic pathway. 2008 Retrovirology Result HIV S149A;S178A 15;25 20;30 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Infectivity of S149A and S178A mutants was efficiently restored following VSV-G incorporation. 2008 Retrovirology Result HIV S149A;S178A 15;25 20;30 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Infectivity of S178A mutant was found slightly increased when pseudotyped with MLV Env (19% compared to 13% observed for MLV Env-S178A and non pseudotyped S178A viruses respectively). 2008 Retrovirology Result HIV S178A;S178A;S178A 15;129;155 20;134;160 Env;Env 83;125 86;128 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Interestingly, pseudotyping with VSV-G significantly restored infectious properties of S149A and S178A mutants to levels observed for VSV-G-WT viruses. 2008 Retrovirology Result HIV S149A;S178A 87;97 92;102 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Interestingly, RT efficiency was enhanced by 38-fold when S149A viral particles contained VSV-G. 2008 Retrovirology Result HIV S149A 58 63 RT 15 17 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. MAGIC-5B cells were next infected with S149A or S178A viruses expressing either VSV-G or HIV Env using doses adjusted to generate comparable levels of strong-stop DNA copies in the infected cells as defined by qPCR experiments. 2008 Retrovirology Result HIV S149A;S178A 39;48 44;53 Env 93 96 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Moreover, progression of RT from early to late steps was stimulated upon incorporation of VSV-G for all viruses studied, with a stronger effect observed for the S149A mutant. 2008 Retrovirology Result HIV S149A 161 166 RT 25 27 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. On the contrary, aberrant aggregates, but no core, were isolated from S109A mutants. 2008 Retrovirology Result HIV S109A 70 75 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Preparations of WT, S149A and S178A cores were then incubated for 2 h at 37 C in conditions that were previously reported to allow core destabilisation. 2008 Retrovirology Result HIV S149A;S178A 20;30 25;35 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. S109A mutant was unable to accomplish RT. 2008 Retrovirology Result HIV S109A 0 5 RT 38 40 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Similar incubation of S178A core particles revealed an increased dissociation rate. 2008 Retrovirology Result HIV S178A 22 27 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Similar RT efficiency was observed in cells infected with VSV-G-S149A, VSV-G-S178A or VSV-G-WT viruses (Figure 3D). 2008 Retrovirology Result HIV S149A;S178A 64;77 69;82 RT 8 10 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. The presence of unambiguous cone-shaped nucleoids was observed in WT and S178A viruses. 2008 Retrovirology Result HIV S178A 73 78 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. The S149A mutation generates subtle core morphological defects despite efficient maturation of CA. 2008 Retrovirology Result HIV S149A 4 9 Capsid 95 97 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. These data confirm replication defects previously reported for S109A, S149A and S178A mutants. 2008 Retrovirology Result HIV S109A;S149A;S178A 63;70;80 68;75;85 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. These results are consistent with data obtained from the biochemical and morphological analyses of entire S109A particles. 2008 Retrovirology Result HIV S109A 106 111 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. This stimulation was also observed for VSV-G-S109A, despite proviral DNA synthesis remaining dramatically inefficient. 2008 Retrovirology Result HIV S109A 45 50 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. To evaluate the impact of S109A, S149A and S178A mutations on core integrity, Cos7 cells were infected with increasing amounts of VSV-G pseudotyped WT or S109A or S149A or S178A virions and challenged with a fixed amount (200 ng CA protein defined by anti-CA ELISA assay) of an HIV-1 reporter virus bearing a GFP sequence in place of the nef gene (HIV-1R7-GFP). 2008 Retrovirology Result HIV S109A;S109A;S149A;S149A;S178A;S178A 26;154;33;163;43;172 31;159;38;168;48;177 Nef;Capsid;Capsid 338;229;256 341;231;258 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Unexpectedly, ERT level was increased by 2.5 fold for the S149A mutant. 2008 Retrovirology Result HIV S149A 58 63 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Viruses were produced by transfection experiments of 293T cells with pNL4.3 or S109A, S149A and S178A mutated molecular clones and used to infect the MAGIC-5B indicator cell line (Figure 2A). 2008 Retrovirology Result HIV S109A;S149A;S178A 79;86;96 84;91;101 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. VSV-G pseudotyping of S149A and S178A mutants rescues 2-LTR circle formation. 2008 Retrovirology Result HIV S149A;S178A 22;32 27;37 LTR 56 59 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. VSV-G-pseudotyped S109A, S149A and S178A viruses (referred below as VSV-G-S109A, VSV-G-S149A and VSV-G-S178A respectively) were normalized for RTase content and used in single-round infectivity assays of the MAGIC-5B cell line (Figure 2C). 2008 Retrovirology Result HIV S109A;S109A;S149A;S149A;S178A;S178A 18;74;25;87;35;103 23;79;30;92;40;108 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. We next examined the capacity of S109A, S149A and S178A mutants to saturate the TRIM family proteins. 2008 Retrovirology Result HIV S109A;S149A;S178A 33;40;50 38;45;55 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. We thus took advantage of these characteristics to evaluate the impact of S109A, S149A and S178A substitutions on structural properties of the corresponding cores. 2008 Retrovirology Result HIV S109A;S149A;S178A 74;81;91 79;86;96 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. When mutant cores were assayed, no significant variation in uncoating efficiency was observed for S149A cores compared to WT (Figure 7B). 2008 Retrovirology Result HIV S149A 98 103 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. When S109A viruses were examined, no core was observed and viruses contained aggregates that were acentric and presented a lobular aspect. 2008 Retrovirology Result HIV S109A 5 10 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. When similar experiments were performed saturating Cos7 cells with increasing amounts of S109A, S149A, S178A viruses, GFP expression levels remained extremely reduced, indicating that TRIM5alpha-mediated restriction of HIV-1R7-GFP replication could not be overcome by the presence in the infected cells, of cores bearing S109A, S149A or S178A mutations. 2008 Retrovirology Result HIV S109A;S109A;S149A;S149A;S178A;S178A 89;321;96;328;103;337 94;326;101;333;108;342 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Additional plasma samples available from subject 3 showed that during the second enfuvirtide interruption the V38A population decayed rapidly after a minimal lag time, declining to below the threshold of detection nearly eleven weeks after enfuvirtide was discontinued. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 110 114 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. After an initial lag of 6 to 12 weeks during which the viral population appeared to be unchanged the V38A mutant population decayed at variable rates. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 101 105 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. As plasma HIV-1 RNA levels subsequently rebounded, the percent of V38A mutant virus increased in parallel, reaching approximately 52% before the end of the enfuvirtide pulse. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 66 70 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Clonal analysis of HR-1 sequences from plasma HIV-1 RNA performed 16 weeks after the interruption showed persistence of the V38A mutation in none of 8 clones (0%) from subject 1, 2 of 8 clones (25%) for subject 2 and 5 of 9 clones (56%) from subject 3 (Table 1). 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 124 128 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Decay of V38A mutant populations during enfuvirtide interruption. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 9 13 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. For example, in subject 3, the initial reduction in plasma HIV-1 RNA was accompanied by an increase in the proportion of V38A mutant from below the limit of detection to about 7%. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 121 125 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. In the absence of enfuvirtide, the V38A mutant was approximately 25% to 65% less fit than wild type. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 35 39 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Increases in the proportion of virus carrying the V38A mutation were detectable within 1 week of the enfuvirtide pulse, and were associated with the rebound in plasma HIV-1 RNA. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 50 54 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. It is noteworthy that for subject 3 the V38A mutant appeared to have a greater fitness disadvantage relative to wild-type during the second enfuvirtide interruption. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 40 44 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Re-emergence of V38A during enfuvirtide pulse therapy. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 16 20 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The relative fitness difference between the V38A mutant and wild-type virus was calculated for each subject (Table 2). 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 44 48 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The time to near-complete replacement of mutant virus by wild type virus appeared to correlate with the duration of ENF treatment prior to the PTI: in subject 1, who received enfuvirtide for 27 weeks, the V38A mutants declined to less than 5% of the viral population by 12 weeks after PTI; in subject 2, who received 33 weeks of enfuvirtide, the V38A population declined to less than 5% by week 22; in subject 3, who received 39 weeks of enfuvirtide, the V38A population declined to less than 5% by week 24. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A;V38A;V38A 205;346;455 209;350;459 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The V38A mutation remained detectable by allele-specific PCR at low levels (approximately 1%) in the viral quasispecies of each subject for 9 to 19 months following enfuvirtide interruption, but had fallen below the limit of detection by clonal analysis. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 4 8 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The V38A mutation was present in 85% or more of the viral quasispecies at the start of the enfuvirtide interruption in all three subjects. 2008 Journal of acquired immune deficiency syndromes (1999) Result HIV V38A 4 8 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. As was seen with the wild-type virus group, the TAMs M41L and K70R were the most common low-frequency mutations. 2008 PLoS medicine Result HIV K70R;M41L 62;53 66;57 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. For the three mutant virus samples positive for M184V, clonal analysis found the mutation to be at frequencies of 5.5%, 1.4%, and 0.6% (DeltaCTs of 7.8, 7.5, and 8.4 cycles, respectively) (sequences submitted to GenBank [http://www.ncbi.nlm.nih.gov/Genbank/index.html], accession numbers EU439613-EU439615). 2008 PLoS medicine Result HIV M184V 48 53 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. Four samples (2% overall) had the following mutations to two drug classes: L90M+M184V, L90M+Y181C, Y181C+T215F, and L90M+M41L+K70R. 2008 PLoS medicine Result HIV K70R;L90M;L90M;L90M;M184V;M41L;T215F;Y181C;Y181C 126;75;87;116;80;121;105;92;99 130;79;91;120;85;125;110;97;104 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. Of the two individuals who had resistance mutations at baseline and maintained virus suppression during the 48-wk course of the study, one person had K103N and the other Y181C; both had been treated with the ABC+3TC+EFV regimen. 2008 PLoS medicine Result HIV K103N;Y181C 150;170 155;175 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. One participant who experienced failure within 2 mo had both the K103N and the M184V mutations, which confer resistance to two drugs in the regimen, EFV and 3TC, respectively. 2008 PLoS medicine Result HIV K103N;M184V 65;79 70;84 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. One participant who had detectable Y181C at baseline experienced virologic rebound with wild-type virus by week 12. 2008 PLoS medicine Result HIV Y181C 35 40 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. One-half of the K70R mutations (5/10) were in samples that also had M41L. 2008 PLoS medicine Result HIV K70R;M41L 16;68 20;72 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. The bulk genotypes of these three specimens revealed only one resistance-associated mutation for each: K70R, K219Q, and K103S, respectively. 2008 PLoS medicine Result HIV K103S;K219Q;K70R 120;109;103 125;114;107 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. The remaining resistance mutation assays identified eight (4%) K103N, seven (3.5%) L90M, three (1.5%) Y181C, two (1.5%) M184V, one (0.5%) T215Y, and four (2%) T215F samples. 2008 PLoS medicine Result HIV K103N;L90M;M184V;T215F;T215Y;Y181C 63;83;120;159;138;102 68;87;125;164;143;107 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. The two individuals with minority K103N and Y181C who successfully suppressed virus had baseline VLs of 104.11 and 103.70 copies/ml, respectively. 2008 PLoS medicine Result HIV K103N;Y181C 34;44 39;49 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. We found that the K70R thymidine analog mutation (TAM) was the most prevalent minority mutation (10/205, 5%), followed by the M41L TAM, which was found in nine samples (4.5%). 2008 PLoS medicine Result HIV K70R;M41L 18;126 22;130 18666824 Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. We identified minority mutations in a total of 30 (10%) samples, which added 6/222 (3%) samples with L90M, 9/101 (9%) with M41L, 14/251 (6%) with K70R, 2/202 (1%) with K103N, 8/200 (4%) with Y181C, 6/260 (2%) with M184V, 10/209 (5%) with T215Y, and 13/209 (6%) with T215F. 2008 PLoS medicine Result HIV K103N;K70R;L90M;M184V;M41L;T215F;T215Y;Y181C 168;146;101;214;123;266;238;191 173;150;105;219;127;271;243;196 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. Among infants who had one or more of these mutations detected, the median level of each of the three NVP resistance mutations (proportion of the viral population with the mutation) was as follows: for infants who were HIV-infected at birth: K103N=4.4%, Y181C=25%, and G190A=3%; for infants who were diagnosed with HIV infection at 2 or 6 weeks of age: K103N=5.4%, Y181C=2.6%, and G190A=18.7%. 2008 The Journal of infectious diseases Result HIV G190A;G190A;K103N;K103N;Y181C;Y181C 268;380;241;352;253;364 273;385;246;357;258;369 HIV infections;HIV infections 314;218 327;230 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. Analysis of K103N, Y181C, and G190A using the LigAmp assay. 2008 The Journal of infectious diseases Result HIV G190A;K103N;Y181C 30;12;19 35;17;24 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. For the 44 samples tested with both ViroSeq and LigAmp, 31 (91.2%) of the 34 K103N, Y181C, and G190A mutations detected by ViroSeq were also detected by LigAmp; two K103N mutations and one Y181C mutation were encoded by unusual nucleotide codons and were not detected by LigAmp. 2008 The Journal of infectious diseases Result HIV G190A;K103N;Y181C;Y181C 95;165;84;189 100;170;89;194 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. In contrast, 7 (87.5%) of the 8 late-infected infants had at least one mutation detected by LigAmp (4 had K103N, 1 had G190A, 1 had K103N+Y181C, and 1 had K103N+G190A, Figure 1D). 2008 The Journal of infectious diseases Result HIV G190A;G190A;K103N;K103N;K103N;Y181C 119;161;106;132;155;138 124;166;111;137;160;143 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. In the extended NVP arm, detection of any NVP resistance mutation (K103N, Y181C, or G190A) was not associated with the number of NVP doses received (median of 14 doses among those with at least one mutation detected vs. 2008 The Journal of infectious diseases Result HIV G190A;K103N;Y181C 84;67;74 89;72;79 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. In the SD NVP arm, one (16.7%) of six infants had a NVP resistance mutation detected by ViroSeq (Y181C), and two additional infants had a NVP resistance mutation detected by LigAmp only (both with Y181C, at 1.4% and 3.5%, Figure 1C). 2008 The Journal of infectious diseases Result HIV Y181C;Y181C 97;197 102;202 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. not detected) were the same for all but one of the 42 infants who had results from both assays; one infant had Y181C detected by ViroSeq as a mixture, but did not have phenotypic resistance detected. 2008 The Journal of infectious diseases Result HIV Y181C 111 116 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. Only 1 (12.5%) of the 8 infants analyzed had NVP resistance detected by ViroSeq (one infant diagnosed at 14 weeks in the extended NVP arm had the K103N mutation). 2008 The Journal of infectious diseases Result HIV K103N 146 151 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. There was only one infant who had NVP resistance that was detected by LigAmp only (1.4% Y181C, with no resistance detected by ViroSeq or PhenoSense). 2008 The Journal of infectious diseases Result HIV Y181C 88 93 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. We compared the portion of infants who had Y181C, K103N, or G190A detected by LigAmp in the two study arms. 2008 The Journal of infectious diseases Result HIV G190A;K103N;Y181C 60;50;43 65;55;48 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. We used a point mutation assay, LigAmp, to detect and quantify HIV variants with the K103N, Y181C, and G190A NVP resistance mutations. 2008 The Journal of infectious diseases Result HIV G190A;K103N;Y181C 103;85;92 108;90;97 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Among mutations selected by raltegravir or elvitegravir that have not been shown to directly reduce susceptibility, L74R, Q95K, E138A/K, and H183P were conserved, whereas V54I, L68V, L74M, T97A, V151I, G163R, and I203M were present in approximately 1% to 2% of isolates from untreated persons (Figure 1). 2008 Retrovirology Result HIV E138A;E138K;G163R;H183P;I203M;L68V;L74M;L74R;Q95K;T97A;V151I;V54I 128;128;202;141;213;177;183;116;122;189;195;171 135;135;207;146;218;181;187;120;126;193;200;175 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Among the CCD mutations shown to directly reduce raltegravir or elvitegravir susceptibility - H51Y, T66I, E92Q, F121Y, G140S, Y143C/H/R, Q146P, S147G, Q148H/R/K, S153Y, N155H/S, and E157Q - only positions 153 and 157 are polymorphic (prevalence >= 0.5%) with S153A and E157Q each present in 1% of sequences (Figures 1). 2008 Retrovirology Result HIV E157Q;E157Q;E92Q;F121Y;G140S;H51Y;N155H;N155S;Q146P;Q148H;Q148K;Q148R;S147G;S153A;S153Y;T66I;Y143C;Y143H;Y143R 182;269;106;112;119;94;169;169;137;151;151;151;144;259;162;100;126;126;126 187;274;110;117;124;98;176;176;142;160;160;160;149;264;167;104;135;135;135 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. E157Q, which decreases raltegravir and elvitegravir susceptibility, was associated with K160Q/T in subtypes A, B, C, and CRF02 and with K156N in three unrelated subtype D isolates. 2008 Retrovirology Result HIV K156N;K160Q;K160T;E157Q 136;88;88;0 141;95;95;5 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. E92G (n = 2), E92D (n = 1), and E92A (n = 1) were present in four isolates. 2008 Retrovirology Result HIV E92A;E92D;E92G 32;14;0 36;18;4 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. F121S (n = 2) and F121L (n = 1) were present in three isolates. 2008 Retrovirology Result HIV F121L;F121S 18;0 23;5 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Finally, the uncommon polymorphism K156N, another accessory INI-resistance mutation is due solely to the presence of this mutation in 9% of subtype B and 5% of subtype D sequences. 2008 Retrovirology Result HIV K156N 35 40 IN 60 63 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. For example, the uncommon polymorphism F139Y is due solely to the presence of this mutation in 8% of subtype A sequences. 2008 Retrovirology Result HIV F139Y 39 44 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. G140E was present in one subtype G isolate. 2008 Retrovirology Result HIV G140E 0 5 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. group M variants at these positions include K14R in 31% of sequences and K160R/Q in 2% of sequences. 2008 Retrovirology Result HIV K14R;K160Q;K160R 44;73;73 48;80;80 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. In contrast, the other uncommon polymorphisms in the alpha4 helix including V151I, S153A, M154I/L, I162V, G163E/K/R, and V165I were not found to covary with each other or with other integrase mutations. 2008 Retrovirology Result HIV G163E;G163K;G163R;I162V;M154I;M154L;S153A;V151I;V165I 106;106;106;99;90;90;83;76;121 115;115;115;104;97;97;88;81;126 IN 182 191 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Of these interacting residues, R20K, K34R, and T206S occurred in 4%, 2%, and 16% of group M sequences, respectively, whereas Q209 and E212 were invariant among group M sequences. 2008 Retrovirology Result HIV K34R;R20K;T206S 37;31;47 41;35;52 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Of these mutations, S230N has been reported in 2.0% of untreated isolates. 2008 Retrovirology Result HIV S230N 20 25 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. R263K (n = 2) and R263G (n = 1) were present in three isolates. 2008 Retrovirology Result HIV R263G;R263K 18;0 23;5 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Six otherwise normal isolates, however, contained the active site mutation E152K. 2008 Retrovirology Result HIV E152K 75 80 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. T66A (n = 2) and T66S (n = 1) were present in three subtype C isolates. 2008 Retrovirology Result HIV T66S;T66A 17;0 21;4 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. T66P was present as part of an electrophoretic mixture in one subtype B and one subtype F isolate. 2008 Retrovirology Result HIV T66P 0 4 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The conservative substitution D232E has also been observed in 2.0% of untreated isolates. 2008 Retrovirology Result HIV D232E 30 35 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The flexible loop, which is generally poorly resolved in crystallographic structures, is completely conserved in group M sequences with the exception of F139Y, which occurred in 12 subtype A infected persons. 2008 Retrovirology Result HIV F139Y 153 158 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The INI-resistance mutation H51Y was present in one subtype A isolate; H51Q (n = 3) and H51P (n = 2) were present in five isolates. 2008 Retrovirology Result HIV H51P;H51Q;H51Y 88;71;28 92;75;32 IN 4 7 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The INI-resistance mutation S147G was present in one CRF01_AE isolate and in one subtype C isolate; S147R was present in one subtype B isolate. 2008 Retrovirology Result HIV S147G;S147R 28;100 33;105 IN 4 7 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The INI-resistance mutation, N155H was present in one subtype B isolate; N155D was present in one subtype D isolate. 2008 Retrovirology Result HIV N155D;N155H 73;29 78;34 IN 4 7 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The INI-resistance mutations Q148H (subtype G) and Q148K (CRF02_AG) were each present in one isolate. 2008 Retrovirology Result HIV Q148H;Q148K 29;51 34;56 IN 4 7 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The nonpolymorphic mutation R263K has been shown to reduce elvitegravir susceptibility by five-fold. 2008 Retrovirology Result HIV R263K 28 33 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The remaining pairs of residues that were associated in two or more subtypes included S119R and A91T/E in subtypes B, C, and CRF02; S119G and T122I in subtypes B and D; K219N and N222K in subtypes C and CRF02, and T124A and S283G in subtypes A and C. 2008 Retrovirology Result HIV A91E;A91T;K219N;N222K;S119G;S119R;S283G;T122I;T124A 96;96;169;179;132;86;224;142;214 102;102;174;184;137;91;229;147;219 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. The uncommon polymorphism V151I which appears to be an accessory INI-resistance mutation is due solely to the presence of this mutation in 10% of subtype B sequences. 2008 Retrovirology Result HIV V151I 26 31 IN 65 68 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. These residues were nonpolymorphic, with the exceptions of the conservative mutations V151I, K156N, and K156R, each of which occurred in 1% of sequences (Figure 1). 2008 Retrovirology Result HIV K156N;K156R;V151I 93;104;86 98;109;91 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Whereas K215N/R, K219N/Q, R269K, and R284G are reported polymorphisms, the remaining positively charged residues were nonpolymorphic. 2008 Retrovirology Result HIV K215N;K215R;K219N;K219Q;R269K;R284G 8;8;17;17;26;37 15;15;24;24;31;42 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Y143H was present in three subtype C isolates and one subtype D isolate. 2008 Retrovirology Result HIV Y143H 0 5 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Y226C/D/F/H, S230N/R, and D232N have been selected in vitro or in vivo by raltegravir and/or elvitegravir. 2008 Retrovirology Result HIV D232N;S230N;S230R;Y226C;Y226D;Y226F;Y226H 26;13;13;0;0;0;0 31;20;20;11;11;11;11 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Among all IN mutants, the F121Y mutant was the most deficient for ST, while retaining normal 3'-P (see Figure 5A). 2008 Biochemistry Result HIV F121Y 26 31 IN 10 12 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Clear example is the E92Q mutant, which has a ST activity that reached level similar to WT with precleaved substrate, whereas it was only around 50% with full-length substrate (compare panels E and A in Figure 5). 2008 Biochemistry Result HIV E92Q 21 25 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Densitometry tracing for the Q148K mutant (Figure 5C) shows this non-processive reaction product (which does not lead to ST) resulting from excision of the last base at the 3'-end of the DNA. 2008 Biochemistry Result HIV Q148K 29 34 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Figure 7A shows a representative experiment demonstrating increased inhibitory effect of elvitegravir on 3'-P mediated by the E92Q mutant. 2008 Biochemistry Result HIV E92Q 126 130 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Figure 8B shows a representative experiments performed with the E92Q mutant. 2008 Biochemistry Result HIV E92Q 64 68 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. For all the mutant enzymes except E92Q both drugs gave similarly weak inhibition as for the WT IN. 2008 Biochemistry Result HIV E92Q 34 38 IN 95 97 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Integrase Q148K displayed the most resistant profile, demonstrating a 77-fold increase for elvitegravir and 27-fold for raltegravir. 2008 Biochemistry Result HIV Q148K 10 15 IN 0 9 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Mutations L74M and F121Y did not contribute to integrase resistance to the drug. 2008 Biochemistry Result HIV F121Y;L74M 19;10 24;14 IN 47 56 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Only one mutant (L74M) appeared normal for both 3'-P and ST. 2008 Biochemistry Result HIV L74M 17 21 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Only two of the mutants L74M and F121Y preserved the same sensibility to the compound as wild-type IN. 2008 Biochemistry Result HIV F121Y;L74M 33;24 38;28 IN 99 101 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Representative 3'-P products for the defective Q148K mutant are shown in Figure 5B-C. 2008 Biochemistry Result HIV Q148K 47 52 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Similar results were obtained with the T66I mutant and wild-type IN, and with elvitegravir. 2008 Biochemistry Result HIV T66I 39 43 IN 65 67 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. T66I, Q148K, S153Y and N155H were at least two-fold more sensitive to raltegravir than to elvitegravir (see numbers above bars in panels D and E). 2008 Biochemistry Result HIV N155H;Q148K;S153Y;T66I 23;6;13;0 28;11;18;4 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The E92Q mutation enhances 3'-P inhibition by raltegravir and elvitegravir. 2008 Biochemistry Result HIV E92Q 4 8 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The L74M mutant was the only one whose ST and 3'-P activities were close to WT IN. 2008 Biochemistry Result HIV L74M 4 8 IN 79 81 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The next most resistance integrase was T66I with 11- and 4.6-fold resistance for elvitegravir and raltegravir, respectively. 2008 Biochemistry Result HIV T66I 39 43 IN 25 34 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The only mutation that markedly impacted 3'-P was Q148K. 2008 Biochemistry Result HIV Q148K 50 55 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The Q148K mutant IN was almost completely unable to catalyze 3'-P. 2008 Biochemistry Result HIV Q148K 4 9 IN 17 19 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The ranking order for the most defective mutants for ST in the dual 3'-P and ST assay was: Q148K < S153Y < T66I < F121Y < N155H < E92Q. 2008 Biochemistry Result HIV E92Q;F121Y;N155H;Q148K;S153Y;T66I 130;114;122;91;99;107 134;119;127;96;104;111 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. These results demonstrate that the E92Q mutation renders IN more resistant to both raltegravir and elvitegravir with regard to ST but sensitize the enzyme to both drugs with respect to 3'-P. 2008 Biochemistry Result HIV E92Q 35 39 IN 57 59 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. This was particularly relevant for the Q148K mutant whose defective 3'-P activity precluded ST determination with the full-length substrate. 2008 Biochemistry Result HIV Q148K 39 44 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Three mutants are selectively defective for ST (F121Y, E92Q and N155H). 2008 Biochemistry Result HIV E92Q;F121Y;N155H 55;48;64 59;53;69 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Together these experiments demonstrate that only one of the mutants, Q148K is severely defective for both 3'-P and ST. 2008 Biochemistry Result HIV Q148K 69 74 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Two mutants (T66I and S153Y) are partially defective for both 3'-P and ST. 2008 Biochemistry Result HIV S153Y;T66I 22;13 27;18 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. We next expressed and analyzed the activity of integrase mutants reported in literature as drug-resistant: T66I, L74M, E92Q, F121Y, Q148K, S153Y, N155H. 2008 Biochemistry Result HIV E92Q;F121Y;L74M;N155H;Q148K;S153Y;T66I 119;125;113;146;132;139;107 123;130;117;151;137;144;111 IN 47 56 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Accordingly, the data suggest that the N-linked glycosylation site ablated by the T271I mutation either contributes to the binding site on FIV Env for CD134, or constrains the conformation of Env such that it may only interact with native feline CD134. 2008 Retrovirology Result HIV T271I 82 87 Env;Env 143;192 146;195 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Effect of the T271I and N342Y mutations on receptor usage by GL8 and CPG41. 2008 Retrovirology Result HIV N342Y;T271I 24;14 29;19 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Effect of the T271I and N342Y mutations on sensitivity to virus neutralising antibody. 2008 Retrovirology Result HIV N342Y;T271I 24;14 29;19 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Given that the T271I and N342Y substitutions were uncommon amongst field isolates and present in neither the F14 and 34TF10 molecular clones, nor the parent biological isolate of FIV Petaluma (not shown), we hypothesised that these mutations may have either been acquired during the process of cell culture adaptation, or amplified from an initial quasispecies during cell culture. 2008 Retrovirology Result HIV N342Y;T271I 25;15 30;20 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. If the T271I mutation conferred enhanced usage of the CRD1 chimera as a receptor then we would predict that direct transfection of the T271I mutant into AH927-FX4P cells expressing the CRD1 chimera would result in enhanced syncytium formation compared to the wild type. 2008 Retrovirology Result HIV T271I;T271I 7;135 12;140 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. If the T271I or N342Y mutations conferred CD134-independence, enhanced CXCR4 expression alone would be sufficient to promote viral entry. 2008 Retrovirology Result HIV N342Y;T271I 16;7 21;12 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. In contrast, introduction of the T271I and Delta2N Envs partially restored the ability of the viruses to use the CRD1 chimera (significant enhancement, t-test). 2008 Retrovirology Result HIV T271I 33 38 Env 51 55 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. in the syncytial assay, the Delta2N mutant Envs showed a marked reduction in syncytia formation compared with the T271I mutants. 2008 Retrovirology Result HIV T271I 114 119 Env 43 47 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Incorporation of the T271I and N342Y mutations into primary isolates of FIV. 2008 Retrovirology Result HIV N342Y;T271I 31;21 36;26 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Introduction of the T271I mutation enhanced syncytia formation in both CD134 and CRD1 chimera expressing cells. 2008 Retrovirology Result HIV T271I 20 25 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. It is possible that glycosylation at these sites protects the virus from virus neutralising antibody (VNA), thus the sensitivity of HIV(FIV) pseudotypes bearing the wild type GL8 Env or the T271I, N342Y and Delta2N mutants to sera from 8 cats infected with GL8 (4 years post-infection) was compared. 2008 Retrovirology Result HIV N342Y;T271I 197;190 202;195 Env 179 182 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Neither the T271 nor the N342Y mutation enhanced or reduced sensitivity to AMD3100 although it was notable that GL8 was significantly more sensitive to antagonism by AMD3100 than CPG41 (at 0.1 mug/ml AMD3100 there was a 100-fold reduction in GL8 entry compared with 5-fold for CPG41), suggesting that CPG41 has a higher affinity for CXCR4 per se. 2008 Retrovirology Result HIV N342Y 25 30 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Neither the WT nor the T271I and N342Y Envs support infection through human CD134 ( and data not shown), however, significant (albeit weak) binding of the WT, T271I and N342Y Fc-SU proteins to human CD134-expressing MCC was detected. 2008 Retrovirology Result HIV N342Y;N342Y;T271I;T271I 33;169;23;159 38;174;28;164 Env 39 43 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Of these substitutions, T271I and N342Y ablated potential sites for N-linked glycosylation in SU. 2008 Retrovirology Result HIV N342Y;T271I 34;24 39;29 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. revealed a significantly more marked enhancement of infection with the T271I and Delta2N viruses than with the WT or N342Y viruses. 2008 Retrovirology Result HIV N342Y;T271I 117;71 122;76 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Similar results were observed with both the GL8 and CPG41 series of Envs indicating that in the presence of the N342Y mutation the enhancement of syncytium formation conferred by T271I was lessened. 2008 Retrovirology Result HIV N342Y;T271I 112;179 117;184 Env 68 72 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. stably expressing full-length feline CD134 (CD134) or a chimeric receptor bearing feline CD134 CRD1 in the context of human CD134 (CRD1), or transduced with vector only (CON) were infected with HIV (FIV) luciferase pseudotypes bearing the wild type (WT), T271I, N342Y or Delta2N Envs derived from GL8 and CPG41 and viral entry was assessed. 2008 Retrovirology Result HIV N342Y;T271I 262;255 267;260 Env 279 283 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Surprisingly, while HIV (FIV) pseudotypes bearing the GL8 and CPG41 Delta2N Envs behaved essentially the same as the pseudotypes bearing the T271I mutant Envs in the entry assay. 2008 Retrovirology Result HIV T271I 141 146 Env;Env 76;154 80;158 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. T271I and N342Y are predicted to lie in a region of FIV SU which may be analogous to the area at the base of the HIV V1 and V2 stem. 2008 Retrovirology Result HIV N342Y;T271I 10;0 15;5 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. T271I does not induce CD134-independence. 2008 Retrovirology Result HIV T271I 0 5 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The addition of exogenous feline or human CXCR4 alone did not enhance infection of the control cells mediated by either the GL8 or CPG41 Envs significantly, irrespective of whether WT, T271I, N342Y or Delta2N. 2008 Retrovirology Result HIV N342Y;T271I 192;185 197;190 Env 137 141 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The cells were then infected with HIV(FIV) luciferase pseudotypes bearing the GL8 and CPG41 Envs (wild type (WT), T271I, N342Y or Delta2N double mutant) and infectivity assayed. 2008 Retrovirology Result HIV N342Y;T271I 121;114 126;119 Env 92 96 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The data are consistent with the T271I mutation removing the requirement of the viral Env for determinants in CRD2, and thus improving its ability to utilise the CRD1 chimaera as an effective viral receptor. 2008 Retrovirology Result HIV T271I 33 38 Env 86 89 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The data suggest that the T271I and N342Y mutations do not alter the affinity of the CXCR4 interaction significantly. 2008 Retrovirology Result HIV N342Y;T271I 36;26 41;31 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The N342Y Envs induced fewer, and smaller syncytia in CD134-expressing cells than the WT Envs and few syncytia in the CRD1-expressing cells. 2008 Retrovirology Result HIV N342Y 4 9 Env;Env 10;89 14;93 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The N342Y mutants behaved ostensibly the same as the WT Envs, demonstrating a marked preference for CD134 over the CRD1 chimera. 2008 Retrovirology Result HIV N342Y 4 9 Env 56 60 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The potential site for N-linked glycosylation targeted by the N342Y mutation was unique to FL4 (in comparison with 35 published amino acid sequences) while the N-linked glycosylation site targeted by the T271I mutation was absent in only three other sequences (n = 34); Aomori 1 and 2 (two related Japanese isolates) and FC2. 2008 Retrovirology Result HIV N342Y;T271I 62;204 67;209 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The predicted N-linked glycosylation sites ablated by the T271I and N342Y mutations are highly conserved among field isolates of FIV and reinstated rapidly (as early as 1 month post-infection) following in vivo replication of mutant virus. 2008 Retrovirology Result HIV N342Y;T271I 68;58 73;63 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The T271I and N342Y mutations were reproduced in molecular clones of FIV GL8 and a chimeric molecular clone bearing the CPG41 Env in the GL8 backbone by site-directed mutagenesis. 2008 Retrovirology Result HIV N342Y;T271I 14;4 19;9 Env 126 129 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. There was no consistent difference in sensitivity to VNA between the WT and the T271I, N342Y and Delta2N mutants, suggesting that this region is not a major target for the humoral response to wild type virus. 2008 Retrovirology Result HIV N342Y;T271I 87;80 92;85 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. These data would suggest that the specificity of receptor binding of the GL8 Env may be dependent on intermolecular interactions in the tertiary complex of the native trimeric Env on virions and accordingly that the T271I mutation modulates this interaction. 2008 Retrovirology Result HIV T271I 216 221 Env;Env 77;176 80;179 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. To address the latter possibility, we examined the sensitivity of viral pseudotypes bearing the WT, T271I or N342Y Envs to the CXCR4 antagonist AMD3100. 2008 Retrovirology Result HIV N342Y;T271I 109;100 114;105 Env 115 119 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Unique amino acid substitutions in SU were identified at T271I, N342Y, W347R and F388L (amino acid numbering is relative to F14). 2008 Retrovirology Result HIV F388L;N342Y;T271I;W347R 81;64;57;71 86;69;62;76 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. We asked whether the T271I, N342Y substitutions were observed in field isolates by comparing the FL4 sequence with published sequences using the BLAST search program. 2008 Retrovirology Result HIV N342Y;T271I 28;21 33;26 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. We next asked whether the T271I or N342Y mutations conferred CD134-independence upon the GL8 and CPG41 Envs. 2008 Retrovirology Result HIV N342Y;T271I 35;26 40;31 Env 103 107 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. We next examined the predicted locations of T271I and N342Y substitutions on the FIV SU protein, comparing the locations with schematic structural models for FIV SU and HIV SU based on predictive algorithms for secondary structure, disulphide bond architecture and informed by the solved crystal structure of HIV Env. 2008 Retrovirology Result HIV N342Y;T271I 54;44 59;49 Env 313 316 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. We therefore asked whether GL8 Fc-SU fusion proteins (proteins that exist primarily as dimers) derived from the WT, T271I or N342Y Envs (trimeric on the native virions) would display the receptor binding properties of their respective parent viruses. 2008 Retrovirology Result HIV N342Y;T271I 125;116 130;121 Env 131 135 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. We therefore compared the ability of the GL8 and CPG41 WT, T271I, N342Y and Delta2N Envs to induce syncytium formation in AH927 cells expressing CD134, the CRD1 chimera or vector only. 2008 Retrovirology Result HIV N342Y;T271I 66;59 71;64 Env 84 88 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. where GL8 WT infection of MCC-CRD1 was 300-fold less efficient, whereas infection with the T271I and Delta2N mutants was reduced by only 27 and 47-fold respectively, suggesting that the presence of the T271I mutation, but not the N342Y mutation, facilitated the interaction between the GL8 Env and CRD1 of CD134. 2008 Retrovirology Result HIV N342Y;T271I;T271I 230;91;202 235;96;207 Env 290 293 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. WT, T271I or N342Y GL8 Env Fc-SUs bound to feline CD134 expressing MCC cells. 2008 Retrovirology Result HIV N342Y;T271I 13;4 18;9 Env 23 26 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. A very low transfer efficiency was found for L23F, DeltaQ44 and L67A, indicating that these Vpr mutants failed to oligomerize even at or near the nuclear envelope. 2008 Retrovirology Result HIV L23F;L67A 45;64 49;68 Env;Vpr 154;92 162;95 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Among the eight mutants, four of them, namely Q3R, W54G, R77Q and R90K, showed a staining pattern similar to that of the wild type fusion proteins with an accumulation at the nuclear rim (compare with Figure 4, panel A2). 2008 Retrovirology Result HIV Q3R;R77Q;R90K;W54G 46;57;66;51 49;61;70;55 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Furthermore, a small but significant FRET was observed between I60A-Vpr-eGFP and its red counterpart (6% in the whole cell; 7% inside the nucleus- figure 5C) even though the I60A-Vpr-eGFP mutant lost its ability to accumulate at the nuclear envelope. 2008 Retrovirology Result HIV I60A;I60A 63;174 67;178 Env;Vpr;Vpr 241;68;179 249;71;182 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. In line with this result, transfection of I60A-Vpr-eGFP with wild type Vpr-mCherry restored up to 100% of the nuclear rim staining of the I60AVpr-eGFP mutant (data not shown). 2008 Retrovirology Result HIV I60A;I60A 42;138 46;142 Vpr;Vpr 47;71 50;74 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Interestingly, this different staining pattern of L23F-Vpr-eGFP and DeltaQ44-Vpr-eGFP compared to the wild type was also found with L23F-Vpr and DeltaQ44-Vpr using immunostaining methodology, indicating that eGFP does not interfere with Vpr distribution. 2008 Retrovirology Result HIV L23F;L23F 50;132 54;136 Vpr;Vpr;Vpr;Vpr;Vpr 55;77;137;154;237 58;80;140;157;240 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Moreover, the W54G mutant was shown to be critical for the interaction with cellular UNG (Uracil DNA glycosilase) and its virion incorporation. 2008 Retrovirology Result HIV W54G 14 18 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. On the contrary, the Vpr L23F, DeltaQ44, I60A and L67A mutants have lost their ability to accumulate at the nuclear rim. 2008 Retrovirology Result HIV I60A;L23F;L67A 41;25;50 45;29;54 Vpr 21 24 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Several amino acids (L23, Q44, I60 and L67) located in the three alpha-helices were changed to F (L23F) or A (I60A, L67A) or deleted (DeltaQ44). 2008 Retrovirology Result HIV I60A;L23F;L67A 110;98;116 114;102;120 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Such an important nuclear envelope localization rescue was not observed with the L23F, DeltaQ44 and L67A Vpr-eGFP mutants. 2008 Retrovirology Result HIV L23F;L67A 81;100 85;104 Env;Vpr 26;105 34;108 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. The L23F and DeltaQ44 Vpr mutants retained their ability to translocate to the nucleus but were poorly incorporated into virions. 2008 Retrovirology Result HIV L23F 4 8 Vpr 22 25 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. The Q3R and R77Q mutants were shown to be impaired in their proapoptotic activity and to be associated with long-term non-progressive HIV-1 infection while the R90K mutant failed to cause the G2/M cell arrest. 2008 Retrovirology Result HIV Q3R;R77Q;R90K 4;12;160 7;16;164 18809675 Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. Finally, to determine whether the superior pharmacokinetics of PC-1505 would require less frequent dosing compared with T-20, we compared the activities of both drugs following dosing every fourth (Q4D) or seventh (Q7D) day and beginning 1 day before or 3 days after inoculation . 2008 The Journal of biological chemistry Result HIV Q4D;Q7D 200;217 203;220 18809675 Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. With the Q4D and Q7D dosing regimens, T-20 caused no significant reduction in HIV-1 RNA or p24, nor did it protect from thymocyte depletion. 2008 The Journal of biological chemistry Result HIV Q4D;Q7D 9;17 12;20 p24 92 95 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. As shown in Figure 5 and Table 5, pseudotypes containing the BR, BR(N283T), BS and Bv1v3 Env were significantly less sensitive to inhibition by BMS-378806 than those with SPL, SPL(T283N), SB, Sv1v3 or Sv1v2 (as demonstrated by non-linear regression analysis with a sigmoidal dose-response model and estimation of IC50 values), while Bv1v2 displayed again an intermediate sensitivity. 2008 Retrovirology Result HIV N283T;T283N 68;180 73;185 Env 89 92 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. As shown in Table 1, statistical analysis of relative infection in the presence of low levels of CD4, irrespective of the levels of CCR5, using the non-parametric Mann-Whitney test (SPSS), indicated that BR, BS, Bv1v3 and BR(N283T) all had statistically significant higher infectivity than SPL, SB and SPL(T283N), as well as than Bv1v2 (except for Bv1v3). 2008 Retrovirology Result HIV N283T;T283N 225;306 230;311 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. As shown in Table 4, we estimated the amount of time needed for each Env to cause the luciferase activity in cell lysates to reach two arbitrary thresholds, 1.0E+4 and 1.0E+5 RLU/second, and found that, in agreement with the differences in fusion efficiency indicated above, BR, BR(N283T), BS and Bv1v3 were able to reach these thresholds in a remarkably shorter time than SPL, SPL(T283N) and SB, while again Bv1v2, DS17, DS17(N283T) and BaL showed an intermediate phenotype. 2008 Retrovirology Result HIV N283T;T283N;N283T 282;382;427 287;387;432 Env 69 72 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Background-subtracted luciferase activity (used as reporter gene) data presented in Figure 3 demonstrated that BR, BR(N283T), BS and Bv1v3 mediated fusion more efficiently than SPL, SPL(T283N) and SB, while Bv1v2, DS17, DS17(N283T) and BaL (a well-characterized, macrophage-tropic Env used as a control) showed an intermediate level of fusion. 2008 Retrovirology Result HIV N283T;T283N;N283T 118;186;225 123;191;230 Env 281 284 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Contrary to Dunfee et al., we did not observe a role for N283 in determining macrophage tropism in these particular Env backgrounds, since the T283N change did not confer macrophage tropism to the SPL Env and the N283T change did not alter the macrophage tropism of the BR or DS17 Env. 2008 Retrovirology Result HIV N283T;T283N 213;143 218;148 Env;Env;Env 116;201;281 119;204;284 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Finally, since there is the potential that the env genes amplified by PCR from total DNA isolated from brain tissue might not fully represent a truly replicating virus present in that tissue, we decided to similarly characterize several env genes obtained by PCR from microglial cells that had been infected with HIV-1DS-br , a viral isolate recovered through co-cultivation of brain tissue derived from an adult, demented AIDS patient with normal MDMs; in addition, one of these clones (DS17) was mutated to generate DS17(N283T) to test as well the potential role of N283 in an additional Env background. 2008 Retrovirology Result HIV N283T 523 528 Env;Env;Env 47;237;590 50;240;593 AIDS 423 427 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Furthermore, we have also constructed chimeric Env containing only the brain-derived V1/V2 region in the context of the spleen Env and vice versa (Bv1v2 and Sv1v2, respectively), and we have also generated the mutant Env SPL(T283N) and BR(N283T) to evaluate the potential role of N283 vs. 2008 Retrovirology Result HIV N283T;T283N 239;225 244;230 Env;Env;Env 47;127;217 50;130;220 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. However, DS17 and DS17(N283T) displayed a mixed phenotype since they had intermediate fusogenicity with low CD4 dependence but a lack of increased avidity for CD4 (as indicated by the sensitivity to inhibition by the anti-CD4 mAb). 2008 Retrovirology Result HIV N283T 23 28 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. However, inhibition experiments with T-1249 and T-1249-BR (Figure 4) demonstrated that pseudotypes with BR, BS, Bv1v3, Bv1v2 and BR(N283T) Env, as well as those with DS17, DS17(N283T) and BaL, were less sensitive than those with SPL and SB Env. 2008 Retrovirology Result HIV N283T;N283T 132;177 137;182 Env;Env 139;240 142;243 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. In addition, the Bv1v3 chimera and the BR(N283T) mutant displayed a similar phenotype to BR and BS, with low CD4 dependence and reduced sensitivity to the anti-CD4 mAb, while the phenotype of the SPL(T283N) mutant was identical to that of SPL and SB. 2008 Retrovirology Result HIV N283T;T283N 42;200 47;205 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. In addition, the mutant Env generated in the background of the DS17 env clone, DS17(N283T), had an identical phenotype to the parental DS17 Env in both CD4 dependence and sensitivity to anti-CD4 mAb. 2008 Retrovirology Result HIV N283T 84 89 Env;Env;Env 24;68;140 27;71;143 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Infection with wild-type BR and BS chimera resulted in luciferase activities 1000-fold above mock infection, and greater than a 100-fold increase was observed with the Bv1v3 chimera, the BR(N283T) mutant and the DS17 and DS17(N283T). 2008 Retrovirology Result HIV N283T;N283T 190;226 195;231 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Similarly, the time needed for the luciferase activity to increase from the lower to the higher threshold reflected the higher fusogenic capacity of BR, BR(N283T), BS and Bv1v3 when compared to SPL, SPL(T283N) and SB, since the former required approximately half the time than the later (Table 4). 2008 Retrovirology Result HIV N283T;T283N 156;203 161;208 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. We then compared all possible pairs and found that dose-response curves for BR, BS, Bv1v3 and BR(N283T) were statistically different from the curves for SPL, SB, SPL(T283N) and Bv1v2, since the null hypothesis of a single best fit curve for the two data sets could be rejected (Table 2). 2008 Retrovirology Result HIV N283T;T283N 97;166 102;171 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. We thus evaluated wild-type, chimeric and mutant Env and found that BR, BS, BR(N283T), DS17 and DS17(N283T) had greater sensitivity to inhibition than SPL, SB, Bv1v3, Bv1v2 and BaL (Figure 6). 2008 Retrovirology Result HIV N283T;N283T 79;101 84;106 Env 49 52 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Although mutations K20T, L63P, and N88S were present with increased frequency in subtype F1 from treated patients compared to untreated individuals (p = 0.0002, p = 0.001, and p = 0.004, respectively), the same differences were not observed when comparing subtype B from treated and untreated groups. 2009 Infection, genetics and evolution Result HIV K20T;L63P;N88S 19;25;35 23;29;39 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. As can be observed in Table 3, I84V was present with increased frequency in subtype B compared with F1. 2009 Infection, genetics and evolution Result HIV I84V 31 35 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. By 36 months, 16% of subtype B strains already carried L90M versus 5% of subtype F1 (p < 0.05). 2009 Infection, genetics and evolution Result HIV L90M 55 59 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Conversely, mutations I54V and V77I were significantly more prevalent in subtype B-infected children. 2009 Infection, genetics and evolution Result HIV I54V;V77I 22;31 26;35 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Conversely, mutations L10V, K20M, L33F, M36I, G73S, and N88D were significantly more prevalent in subtype B viruses from treated patients compared to untreated individuals (p = 0.002, p = 0.005, p = 0.02, p < 0.0001, p = 0.0005, and p = 0.02, respectively), but this was not true for subtype F1. 2009 Infection, genetics and evolution Result HIV G73S;K20M;L10V;L33F;M36I;N88D 46;28;22;34;40;56 50;32;26;38;44;60 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In agreement with previous analyses, 13.3% (15/113) of subtype B-infected patients under IDV, RTV and/or APV for an average time of 21.6 months presented I84V, while only 2.6% (3/117) of the subtype F1 isolates under 26.4 months of exposure to these PI, showed that mutation (p = 0.002). 2009 Infection, genetics and evolution Result HIV I84V 154 158 PI 250 252 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In agreement with previous analyses, the only significant difference (p = 0.008) was for the prevalence of I84V in subtype B (18.9%, 10/53 strains) and F1 (4.6%, 4/88) strains from patients matched for the same treatment time with IDV, RTV and/or APV. 2009 Infection, genetics and evolution Result HIV I84V 107 111 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In the global dataset, D30N was only seen in isolates from patients treated with NFV and I84V in patients treated with IDV, RTV and/or APV. 2009 Infection, genetics and evolution Result HIV D30N;I84V 23;89 27;93 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In untreated patients, mutations L10V, K20R, and M36I were significantly more frequent in subtype F1 isolates, while mutations L63P, A71T, and V77I were more prevalent in subtype B isolates. 2009 Infection, genetics and evolution Result HIV A71T;K20R;L10V;L63P;M36I;V77I 133;39;33;127;49;143 137;43;37;131;53;147 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Mutation G73S was more prevalent in subtype Binfected adults. 2009 Infection, genetics and evolution Result HIV G73S 9 13 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Ninety-seven percent of isolates with V82A/F/T/S mutations were from patients treated with IDV, RTV and/or LPV, and 89% of those with L90M were from patients treated with NFV and/or SQV. 2009 Infection, genetics and evolution Result HIV L90M;V82A;V82F;V82S;V82T 134;38;38;38;38 138;48;48;48;48 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Of note, M46I was more frequent than M46L in subtype B isolates, while M46L was more frequent than M46I in subtype F1 isolates (Table 3). 2009 Infection, genetics and evolution Result HIV M46I;M46I;M46L;M46L 9;99;37;71 13;103;41;75 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Only V82L was present with increased frequency in subtype B (6.7%) and F1 (8.3%, not shown) isolates from children compared to subtype B (0%) and F1 (0.8%) isolates from adults (Table 2). 2009 Infection, genetics and evolution Result HIV V82L 5 9 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. The major protease mutations V32I and I47V/A and the minor mutations L10R, I54M, and G73C/T/A were not observed in subtype B and F1 viruses from treated or untreated patients in this study (Tables 2 and 3). 2009 Infection, genetics and evolution Result HIV G73A;G73C;G73T;I47A;I47V;I54M;L10R;V32I 85;85;85;38;38;75;69;29 93;93;93;44;44;79;73;33 PR 10 18 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. To avoid confounding effects of the selection of L90M by NFV, SQV and other PI, it was possible to restrict this analysis to patients exclusively subjected to NFV as the unique PI over time. 2009 Infection, genetics and evolution Result HIV L90M 49 53 PI;PI 76;177 78;179 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Twenty-one percent (21/102) of subtype B-infected patients under NFV for an average time of 18.7 months presented D30N, while only 9.6% (10/104) of the subtype F1 isolates under 19.6 months of NFV exposure, showed that mutation (p = 0.02). 2009 Infection, genetics and evolution Result HIV D30N 114 118 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Accordingly, we were also interested in the ability of RT enzymes containing TAMs and K65R. 2008 AIDS (London, England) Result HIV K65R 86 90 RT 55 57 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. As described above, silent mutations at codons 65 and 66 in the RT gene are highly associated with TAMs, and in particular D67N. 2008 AIDS (London, England) Result HIV D67N 123 127 RT 64 66 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Furthermore, the silent AAA to AAG change at codon 65 in combination with the D67N and K70R (template RH3) had minimal effect of the overall polymerization pattern of the enzyme. 2008 AIDS (London, England) Result HIV D67N;K70R 78;87 82;91 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. However, on templates that included the K65R mutation (RH4), TAM67/K65R RT exhibited a very strong tendency to pause at codons 65, 66 and 67. 2008 AIDS (London, England) Result HIV K65R;K65R 67;40 71;44 RT 72 74 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. However, when the K65 or K66 AAA to AAG mutations were added to the background of the D67N and K70R mutational changes (templates RH3 and RH2, respectively), these pausing and/or dissociation events were largely alleviated (Figures 3A, 3C). 2008 AIDS (London, England) Result HIV D67N;K70R 86;95 90;99 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. In comparison with WT and TAM67 HIV-1 RT, the TAM67/K65R enzyme exhibited a decreased tendency to pause at codons 66 and 67 on the RH1 template. 2008 AIDS (London, England) Result HIV K65R 52 56 RT 38 40 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. In particular, at position 67 of the RT, 7% of wild-type D67 samples had the 65K and/or 66K silent mutations, compared with over 80% of samples with the D67N substitution (p<<0.001). 2008 AIDS (London, England) Result HIV D67N 153 157 RT 37 39 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Interestingly, for both RT enzymes, the introduction of the K65R mutation (AAA to AGA) into the RNA template (template RH4) also alleviated the replication block resulting from the 67 and 70 mutational changes (Figure 3B, 3C). 2008 AIDS (London, England) Result HIV K65R 60 64 RT 24 26 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Interestingly, the introduction of silent mutation into templates with 67N/70R/K65R mutations does not alleviate the block experienced by RT with K65R+TAMs. 2008 AIDS (London, England) Result HIV K65R;K65R 79;146 83;150 RT 138 140 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. K65R) and TAMs has previously been reported at the genomic, viral and enzyme level in subtype B RT, indicating that the virus cannot readily accommodate both TAMs and K65R in RT. 2008 AIDS (London, England) Result HIV K65R;K65R 167;0 171;4 RT;RT 96;175 98;177 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Note that the amino acid substitution K65R has been implicated in resistance to many of these agents, and is itself antagonistic to TAMs. 2008 AIDS (London, England) Result HIV K65R 38 42 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Silent Mutations Compensate for Replication Block of D67N/K70R. 2008 AIDS (London, England) Result HIV D67N;K70R 53;58 57;62 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. TAM67/K65R RT) to copy RNA templates that contained codon changes at positions 65, 66, 67 and 70 (Figure 3D). 2008 AIDS (London, England) Result HIV K65R 7 11 RT 11 13 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. To address a possible mechanism by which the silent mutations at codons 65 and 66 in the HIV-1 RT gene might affect virus replication, we assessed the ability of recombinant HIV-1 RT that was WT or contained the TAMs D67N, K70R, T215F and K219Q (TAM67 RT) to copy RNA templates that spanned codons 62 to 77 in RT and included different combinations of mutations at codons 65 (AAA, AGA, AAG), 66 (AAA, AAG), 67 (GAC, AAC) and 70 (AAA, AGA). 2008 AIDS (London, England) Result HIV D67N;K219Q;K70R;T215F 217;239;223;229 221;244;227;234 RT;RT;RT;RT 95;180;252;310 97;182;254;312 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Together, these results suggest that mutations at codons 65 and 66 in the RNA template compensate for a replication block triggered by the D67N/K70R mutations. 2008 AIDS (London, England) Result HIV D67N;K70R 139;144 143;148 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Under steady-state kinetic conditions, both the WT and TAM67 RTs exhibited a stronger tendency to pause/dissociate at codons 65 and 66 on RNA templates containing the D67N/K70R mutations (template RH1) in comparison to the wild-type sequence (Figure 3A, 3C). 2008 AIDS (London, England) Result HIV D67N;K70R 167;172 171;176 RT 61 64 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. All 27 patients harboured the G190A and A98S mutations. 2008 AIDS (London, England) Result HIV A98S;G190A 40;30 44;35 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. As shown, viral variants harbouring mutations to NRTIs, including revertants at codon 215 (T215C/D/I/N/S), thymidine analogue mutations, and M184V, as well as to PIs were less frequent in clustered transmissions. 2008 AIDS (London, England) Result HIV M184V;T215C;T215D;T215I;T215N;T215S 141;91;91;91;91;91 146;104;104;104;104;104 NRTI;PI 49;162 54;165 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. In addition, cluster C represents an MDR transmission network, wherein all four PHIs harboured K103N and three of the four also harboured L10I, I54V, A71V, V82A/I/T, I84I/V, and L90M. 2008 AIDS (London, England) Result HIV A71V;I54V;I84I;I84V;K103N;L10I;L90M;V82A;V82I;V82T 150;144;166;166;95;138;178;156;156;156 154;148;172;172;100;142;182;160;164;164 HIV infections 80 84 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. K103N, V108I, G190A, associated with resistance to NNRTIs. 2008 AIDS (London, England) Result HIV G190A;V108I;K103N 14;7;0 19;12;5 NNRTI 51 57 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. L90M, V82I, that have limited impact on drug susceptibility and viral replicative capacity. 2008 AIDS (London, England) Result HIV V82I;L90M 6;0 10;4 19005274 Transmission networks of drug resistance acquired in primary/early stage HIV infection. Such forward transmission of NNRTI resistance in clusters was independent of the G190A mutation (Fig, 1). 2008 AIDS (London, England) Result HIV G190A 81 86 NNRTI 29 34 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Approximately 10% of the KR186, 7AA IN bound chromatin and the association of the V165A and A179P IN with chromatin was also reduced to approximately 70% of the wild type level. 2008 Retrovirology Result HIV A179P;V165A 92;82 97;87 IN;IN 36;98 38;100 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. HIV-1 encoding the lethal phenotype-defective IN mutations are replication defective and the defect can be partially complemented by the IN D64E mutant. 2008 Retrovirology Result HIV D64E 140 144 IN;IN 46;137 48;139 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. If true, the complementation with the D64E mutant may restore the infecting ability of these lethal phenotype-defective IN mutants. 2008 Retrovirology Result HIV D64E 38 42 IN 120 122 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. In order to confirm that the wild type IN and the D64E and K136A mutants were indeed associated with the chromatin, the chromatin-bound P1 fractions were further treated with DNase and salt to release the chromatin-bound proteins into the soluble fraction (S2). 2008 Retrovirology Result HIV D64E;K136A 50;59 54;64 IN 39 41 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. In order to further identify the critical amino acid(s) or motif(s) in IN important in the induction of the lethal phenotype, various IN mutants, including F1A, K136A, K159P, V165A, A179P, KR186,7AA, KK215,9AA and RK263,4AA, were introduced into HP16 yeast cells. 2008 Retrovirology Result HIV A179P;F1A;K136A;K159P;V165A 182;156;161;168;175 187;159;166;173;180 IN;IN 71;134 73;136 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. In parallel, the VSV-G-pseudotyped wild type virus (vINwt) and the IN class I mutant D64E virus (vD64E) were also included as controls. 2008 Retrovirology Result HIV D64E 85 89 IN 67 69 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. In particular, cells transformed with the IN mutants V165A, A179P or KR186,7AA had growth rate similar to the yeast cells transformed with empty vector, indicating that these three mutations, all located in the C-terminal region of the IN catalytic core domain, are unable to induce the lethal phenotype in the HP16 yeast strain. 2008 Retrovirology Result HIV A179P;V165A 60;53 65;58 IN;IN 42;236 44;238 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Interestingly, all three IN mutants (V165A, A179P, KR186,7AA) which lost their chromatin-binding ability failed to interact with LEDGF/p75. 2008 Retrovirology Result HIV A179P;V165A 44;37 49;42 IN 25 27 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Interestingly, when C8166 cells were infected with viruses containing two different IN mutant proteins, such as D64E/V165A, D64E/A179P, or D64E/KR186,7AA, the luc values were much higher than infection with D64E or V165A virus. 2008 Retrovirology Result HIV A179P;D64E;D64E;D64E;D64E;V165A;V165A 129;112;124;139;207;117;215 134;116;128;143;211;122;220 IN 84 86 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Interestingly, when C8166 cells were infected with VSV-G-pseudotyped viruses containing the chromatin binding-defective IN mutants, the levels of luc activity were similar to the D64E mutant virus throughout the 6-day period. 2008 Retrovirology Result HIV D64E 179 183 IN 120 122 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Moreover, like the wild type IN, the D64E/D116A mutant induced the lethal phenotype in a dose-dependent manner in the presence of galactose. 2008 Retrovirology Result HIV D116A;D64E 42;37 47;41 IN 29 31 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Nevertheless, the data presented here indicate that the lethal phenotype-defective mutations and the D64E substitution affect different steps during the viral replication. 2008 Retrovirology Result HIV D64E 101 105 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Of note, the complementation level of D64E for A179P and KR186,7AA mutants was lower than that of V165A mutant. 2008 Retrovirology Result HIV A179P;D64E;V165A 47;38;98 52;42;103 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Previous studies have indicated that the catalytic activity of IN may be required for IN-induced lethality in yeast since introduction of an IN catalytic mutant (D116A) was not lethal in the yeast strain AB2. 2008 Retrovirology Result HIV D116A 162 167 IN;IN;IN 63;86;141 65;88;143 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Results showed that up to 20-25% of the wild type IN and mutants D64E and K136A were detected in the chromatin-bound P1 fraction. 2008 Retrovirology Result HIV D64E;K136A;D64E;K136A 66;75;65;74 70;80;69;79 IN 50 52 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Similar to what was observed in yeast cells, the V165A, A179P and KR186,7AA mutants were exclusively present in the non chromatin-bound S1 fraction. 2008 Retrovirology Result HIV A179P;V165A 56;49 61;54 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Since the V165A, A179P and KR186,7AA IN mutants, but not class I mutant D64E, failed to both induce yeast lethality and associate with chromatin, it is tempting to postulate that the lethal phenotype-defective mutations affect a different step in the HIV-1 replication than the D64E mutant. 2008 Retrovirology Result HIV A179P;D64E;D64E;V165A 17;72;278;10 22;76;282;15 IN 37 39 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. the D64E and V165A mutant viruses only induced a basal level of luc activity. 2008 Retrovirology Result HIV D64E;V165A 4;13 8;18 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. The infection of the class I mutant D64E virus resulted only in a basal level of luc activity that was approximately 104-fold lower than the wild type. 2008 Retrovirology Result HIV D64E 36 40 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. These differences may be due to the fact that the non-conservative substitutions in A179P or KR186,7AA mutants profoundly affect the functions of IN, including its catalytic activity. 2008 Retrovirology Result HIV A179P 84 89 IN 146 148 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. These results indicate that, like the class I D64E mutant virus, the chromatin binding-deficient V165A, A179P and KR186,7AA mutant viruses were replication defective in C8166 cells. 2008 Retrovirology Result HIV A179P;D64E;V165A 104;46;97 109;50;102 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. These results were further supported by the observation that there was no complementation between V165A and KR186,7AA mutants when they were co-incorporated in the virus. 2008 Retrovirology Result HIV V165A 98 103 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. To test whether the IN catalytic mutants could induce the lethal phenotype in HP16 yeast strain, we first introduced the class I IN mutants D64E, D116A and the double mutant (D64E/D116A) into yeast strain HP16 and determined their effect on yeast growth. 2008 Retrovirology Result HIV D116A;D116A;D64E;D64E 146;180;140;175 151;185;144;179 IN;IN 20;129 22;131 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Total viral DNA synthesis during infections with the V165A-, A179P- and KR186,7AA-containing viruses was similar to that following infection with the wild type and D64E mutant viruses. 2008 Retrovirology Result HIV A179P;D64E;V165A 61;164;53 66;168;58 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. A second HIV-1 IN that contains a K211S substitution, also in the 3CSF185H background, cleaved the HIV-1 U5 but not the ASV U3 or MLV U5 substrates. 2009 Journal of molecular biology Result HIV K211S 34 39 IN 15 17 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. As previously reported, the G163R Q164V V165L chimera in the 3CSF185H background cleaved both HIV-1 U5 and ASV U3 LTR end substrates (Figure 2). 2009 Journal of molecular biology Result HIV G163R;Q164V;V165L 28;34;40 33;39;45 LTR 114 117 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. D229I S230E was unique among these mutants in that it possessed more 3' processing activity towards the HIV-1 substrate than 3CSF185H IN (Figure 3A). 2009 Journal of molecular biology Result HIV S230E;D229I 6;0 11;5 IN 134 136 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. HIV-1 IN with a T125S substitution resulted in an enzyme that increased its 3' processing reaction relative to 3CSF185H (126%, SD=11.7). 2009 Journal of molecular biology Result HIV T125S 16 21 IN 6 8 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. In contrast, Q44N, L68E E69P, D229I S230E, and D253N maintained the ability to cleave the HIV-1 substrate, and gained the ability to cleave the ASV substrates to different extents (Figure 3). 2009 Journal of molecular biology Result HIV D229I;D253N;E69P;L68E;Q44N;S230E 30;47;24;19;13;36 35;52;28;23;17;41 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. In the case of the V72W IN mutant, which has reduced 3' processing of HIV-1 substrates (79 % compared to wild-type, SD=8.6), second site substitutions at F121, T125, and V151 have been reported. 2009 Journal of molecular biology Result HIV V72W 19 23 IN 24 26 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. Of the chimeras tested, S39T K42H, Y227I, N254D, K258T R262S showed decreased or no activity with HIV-1 substrates and did not cleave the ASV substrates (data not shown). 2009 Journal of molecular biology Result HIV K258T;K42H;N254D;R262S;S39T;Y227I 49;29;42;55;24;35 54;33;47;60;28;40 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. Several amino acid changes introduced into the HIV-1 IN (L68E and E69P, V72W, and H171K and L172Q) that alter 3' processing disrupt the strand transfer activity towards the HIV-1 substrates. 2009 Journal of molecular biology Result HIV E69P;H171K;L172Q;L68E;V72W 66;82;92;57;72 70;87;97;62;76 IN 53 55 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. The activity of the Q221S mutant in both 3' end processing and strand transfer was similar to that of K211S (data not shown). 2009 Journal of molecular biology Result HIV K211S;Q221S 102;20 107;25 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. The chimeras were assembled in a 3CSF185H background, an enzyme with four amino acid substitutions (C56S, C65S, C280S, and F185H) to improve solubility. 2009 Journal of molecular biology Result HIV C280S;C56S;C65S;F185H 112;100;106;123 117;104;110;128 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. The K211S mutant showed near wild-type 3' processing while the K219S mutant still had 3' processing activity towards a HIV-1 substrate though less than wild type (Figure 5). 2009 Journal of molecular biology Result HIV K211S;K219S 4;63 9;68 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. Thus, the K219S enzyme lost the ability to strand transfer with a decrease in 3' processing while the K211S and the Q221S mutants had no detectable affect on either activity. 2009 Journal of molecular biology Result HIV K211S;K219S;Q221S 102;10;116 107;15;121 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. Twelve of the fifteen amino acid exchanges that affect LTR recognition in the processing reaction were combined into a single construct (V72W S153R K160D I161R G163R Q164V V165L H171K L172Q D229I S230E D253N) and purified from the soluble fraction. 2009 Journal of molecular biology Result HIV D229I;D253N;G163R;H171K;I161R;K160D;L172Q;Q164V;S153R;S230E;V165L;V72W 190;202;160;178;154;148;184;166;142;196;172;137 195;207;165;183;159;153;189;171;147;201;177;142 LTR 55 58 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. We therefore assembled HIV-1 IN mutants with K211S, K219S, and Q221S, substitutions, respectively. 2009 Journal of molecular biology Result HIV K211S;K219S;Q221S 45;52;63 50;57;68 IN 29 31 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. When tested in the strand transfer assay using pre-processed HIV-1 LTR DNA, we observed that the K211S mutant was as active as wild-type while the K219S mutant was inactive. 2009 Journal of molecular biology Result HIV K211S;K219S 97;147 102;152 LTR 67 70 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. When the V72W and T125S substitutions were combined into the same enzyme, the resultant chimera had a 3' processing activity equivalent to 3CSF185H (97%, SD=2.0). 2009 Journal of molecular biology Result HIV T125S;V72W 18;9 23;13 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. As shown in Figure 4, the vif mutations were stable from one to three weeks post-inoculation for all three macaques inoculated with SHIVVifAAQYLA, but by 4 weeks post-inoculation the S147A amino acid substitution changed to a threonine in two of the macaques RPL10 and RAK10. 2009 Virology Result HIV S147A 183 188 Vif 26 29 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. DNA from lymphoid organs obtained at necropsy from RAK10 and RPL10 also showed the A147T mutation whereas macaque RCS10 maintained S147A amino acid substitution. 2009 Virology Result HIV A147T;S147A 83;131 88;136 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. The L148A substitution was found to be stable during the course of infection for all three macaques and in lymphoid organs analyzed at necropsy. 2009 Virology Result HIV L148A 4 9 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. At 0.3 mM ATP, the AZTR/Q509L RT was more efficient at excising AZT-MP than the AZTR enzyme, and this increase in excision efficiency was driven predominantly by an increase in the burst concentration and not by an increase in rate (Table 2). 2008 Biochemistry Result HIV Q509L 24 29 RT 30 32 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. At 3 mM ATP, there was no difference in excision activity between the AZTR/Q509L and AZTR enzymes. 2008 Biochemistry Result HIV Q509L 75 80 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Because RT dissociates and rebinds to TRNA16/PAZT to generate TRNA10/PAZT, we hypothesized that Q509L might decrease the efficiency of this cleavage by directly affecting the binding interactions involved. 2008 Biochemistry Result HIV Q509L 96 101 RT 8 10 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. By comparison, TAMs, which include M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E, increase the ability of HIV-1 RT to excise a chain-terminating NRTI-monophosphate (NRTI-MP) from a DNA chain. 2008 Biochemistry Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 41;73;73;47;53;35;60;60 45;80;80;51;58;39;67;67 NRTI;NRTI;RT 145;165;112 149;169;114 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. By contrast, differences in AZT-MP excision between the AZTR and AZTR/Q509L enzymes were evident on the RNA/DNA T/P at low but not high concentrations of ATP (Figure 1B). 2008 Biochemistry Result HIV Q509L 70 75 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Cumulative Effect of Q509L in Assays That Evaluate Multiple AZT-TP Incorporation and AZT-MP Excision Events. 2008 Biochemistry Result HIV Q509L 21 26 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Figure 2A shows autoradiograms of the RNase H products generated during ATP-mediated excision assays by WT, AZTR, and AZTR/Q509L RT. 2008 Biochemistry Result HIV Q509L 123 128 RT 129 131 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. However, as described above, the rate of appearance of the TRNA10/PAZT significantly decreased for AZTR/Q509L RT compared with the WT and AZTR enzymes (Figure 4B). 2008 Biochemistry Result HIV Q509L 104 109 RT 110 112 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In comparison with the other two enzymes, AZTR/Q509L RT accumulated more cleavage product with RNA/DNA duplex length of 15 or 16 nucleotides. 2008 Biochemistry Result HIV Q509L 47 52 RT 53 55 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In the experiments described below, we examined both the discrimination and excision pheno-types to elucidate the mechanism(s) by which Q509L confers zidovudine resistance. 2008 Biochemistry Result HIV Q509L 136 141 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In the presence of 3 mM ATP, the AZTR/Q509L was significantly more efficient than the AZTR enzyme in synthesizing the full-length product on the RNA/DNA T/P (Figure 3) but not DNA/DNA T/P (data not shown). 2008 Biochemistry Result HIV Q509L 38 43 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. It should also be noted that the efficiency of AZTMP excision by AZTR/Q509L RT on the 10 nucleotide duplex was significantly greater than that of either WT or AZTR enzymes (Figure 2C), indicating a second mechanism whereby Q509L enhances AZT-MP excision. 2008 Biochemistry Result HIV Q509L;Q509L 70;223 75;228 RT 76 78 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Our analyses of RNase H activity (Figure 2) demonstrated that Q509L in RT decreases the formation of a secondary RNase H cleavage product that reduces the RNA template to 19 nucleotides (nt) and the RNA/DNA T/P duplex length to 10 nt. 2008 Biochemistry Result HIV Q509L 62 67 RT 71 73 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Since all three enzymes exhibited similar IC50 values, we must conclude that Q509L does not affect the binding interaction between RT and TRNA16/PAZT when the enzyme is bound in a polymerase- or excision-competent mode. 2008 Biochemistry Result HIV Q509L 77 82 Pol;RT 180;131 190;133 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The concentrations of trap required to inhibit 50% of the enzyme's excision activity were calculated to be 47 +- 35 nM, 58 +- 37 nM, and 65 +- 20 nM trap for the WT, AZTR, and AZTR/Q509L RTs, respectively (Figure 5). 2008 Biochemistry Result HIV Q509L 181 186 RT 187 190 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The concentrations of trap required to inhibit 50% of the enzyme's RNase H activity were calculated to be 4.5 +- 0.4 muM, 4.2 +- 1.4 muM, and 2.2 (0.8 muM trap for the WT, AZTR, and AZTR/Q509L RTs, respectively (Figure 5). 2008 Biochemistry Result HIV Q509L 187 192 RT 193 196 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The data described above suggested to us that Q509L did not exert a direct effect on ATP-mediated excision because there was no change in the rates at which HIV-1 RT unblocked the AZT-MP chain-terminated primer on either DNA/DNA or RNA/DNA T/P. 2008 Biochemistry Result HIV Q509L 46 51 RT 163 165 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The data from these experiments show that the initial rates of RNase H cleavage were similar for the WT, AZTR, and AZTR/Q509L enzymes (Figure 4A). 2008 Biochemistry Result HIV Q509L 120 125 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The data show that each of the three recombinant enzymes was equally sensitive to inhibition by AZT-TP (Table 1), indicating that Q509L does not confer zidovudine resistance via a discrimination phenotype. 2008 Biochemistry Result HIV Q509L 130 135 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The efficiency of AZT-MP excision by AZTR/Q509L RT was identical to that of the AZTR enzyme on DNA/DNA T/P, and this result was independent of the ATP concentration used in the assay (Figure 1A; Table 2). 2008 Biochemistry Result HIV Q509L 42 47 RT 48 50 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The enzymes included in this study were WT RT, D67N/K70R/T215F (AZTR) RT, and AZTR/Q509L RT. 2008 Biochemistry Result HIV D67N;K70R;T215F;Q509L 47;52;57;83 51;56;62;88 RT;RT;RT 43;70;89 45;72;91 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The finding that Q509L significantly decreases the formation of this 10 nucleotide duplex provides one mechanism by which this mutation enhances AZT-MP excision. 2008 Biochemistry Result HIV Q509L 17 22 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The lower IC50 value for the AZTR/Q509L RT implies that this enzyme is more sensitive to inhibition by trap and therefore likely dissociates more readily from the TRNA16/PAZT substrate. 2008 Biochemistry Result HIV Q509L 34 39 RT 40 42 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The mutations K65R, K70E, L74V, Q151 M, and M184V increase the selectivity of RT for incorporation of the natural dNTP substrate versus the NRTI-triphosphate (NRTI-TP). 2008 Biochemistry Result HIV K65R;K70E;L74V;M184V;Q151M 14;20;26;44;32 18;24;30;49;38 NRTI;NRTI;RT 140;159;78 144;163;80 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The results show that no cleavage products are formed that have RNA/DNA duplexes less than 15-nt for either the WT RT (Figure 4C) or for the AZTR and AZTR/Q509L enzymes (data not shown). 2008 Biochemistry Result HIV Q509L 155 160 RT 115 117 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. There was also a significant decrease in the rate of appearance of a cleavage event that reduces the RNA/DNA duplex length to 10 nucleotides (Figure 2A,B); the apparent rate constants for this RNase cleavage event were calculated to be 0.034 min-1, 0.036 min-1, and 0.016 min-1for the WT, AZTR, and AZTR/Q509L RTs, respectively. 2008 Biochemistry Result HIV Q509L 304 309 RT 310 313 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. These results reinforce the findings described in Figure 1 and further demonstrate that the Q509L mutation augments zidovudine resistance on an RNA/DNA T/P but not a DNA/DNA T/P. 2008 Biochemistry Result HIV Q509L 92 97 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Thus, these studies did not inform if Q509L also affected the primary RNase H cleavage event, which occurs in the millisecond time range, or the sequence of cleavage and T/P dissociation events that generate the 19 nt RNA product. 2008 Biochemistry Result HIV Q509L 38 43 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. To determine whether Q509L directly altered the efficiency of AZT-MP excision, we investigated the ability of WT and mutant RTs to excise AZT-MP from chain-terminated DNA/DNA and RNA/DNA T/P at both high (3 mM) and low (0.3 mM) concentrations of ATP (Figure 1). 2008 Biochemistry Result HIV Q509L 21 26 RT 124 127 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. To determine whether the Q509L mutation affects the ability of RT to discriminate against the incoming nucleotide analogue, we determined the concentration of AZT-TP required to inhibit the incorporation of dTTP into the homopolymeric poly(rA)-oligo(dT)18 T/P by WT or mutant enzymes under steady-state assay conditions. 2008 Biochemistry Result HIV Q509L 25 30 RT 63 65 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. A variation occurred in the case of H121N TGs. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N 36 41 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Additive ultrastructural damage to Y955C TGs following AZT-HAART was not easily discernable. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 35 40 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Alternatively, mutant TK2 TGs (H121N and I212N) alone also exhibited increased mtDNA in myocardial extracts at 3 weeks, in this case independent of AZT-HAART treatment. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N;I212N 31;41 37;46 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. At 10 weeks, mtDNA density for vehicle-treated H121N TGs resembled that of WTs, however, AZT-HAART-treated H121N TGs exhibited decreased mtDNA density (46%) compared to AZT-HAART-treated WT controls. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N;H121N 47;107 52;112 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Exceptions included the vehicle-treated native TK2 TGs in which mtDNA density increased at 10 weeks compared to 3 weeks (P<0.05) and H121N TGs in which mtDNA density decreased at 10 weeks compared to 3 weeks (P<0.001). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N 133 138 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. H121N and I212N TK2 mutant TGs had relatively few changes following AZT-HAART treatment, whereas native TK2 TGs demonstrated irregular shaped mitochondria with less prominent, truncated cristae that resembled that of WTs undergoing similar treatment (Figure 6b). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV I212N;H121N 10;0 15;5 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. H121N mutant TK2 had no effect. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N 0 5 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. However, both vehicle- and all AZT-HAART-treated mutant TGs (Y955C, H121N, and I212N) exhibited significant changes. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N;I212N;Y955C 68;79;61 73;84;66 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. I212N mutant TK2 TGs exhibited LVH, independent of AZT-HAART (Figure 4a). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV I212N 0 5 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. I212N TK2 TGs continued to demonstrate increased mtDNA abundance as a transgenic effect, independent of AZT-HAART (Figure 3b). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV I212N 0 5 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. In addition, Y955C LVH was further exacerbated by AZT-HAART (Figure 4a), suggesting a synergy of effects induced by both the transgene and NRTI treatment. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 13 18 NRTI 139 143 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. In contrast, H121N and I212N mtDNA densities increased (60-90%) over WTs. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N;I212N 13;23 18;28 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. In contrast, H121N TGs exhibited control levels of mtDNA in both vehicle- and AZT-HAART-treated cohorts compared to WT littermates at 10 weeks (Figure 3b). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N 13 18 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Likewise, Y955C TGs exhibited LVH with the greatest change in LV mass among all the TG cohorts. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 10 15 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. LVEDD increased in H121N and I212N TGs when combined with AZT-HAART (Figure 5b). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N;I212N 19;29 24;34 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. The absolute decrease in mtDNA abundance induced in the Y955C TGs (vehicle treated) worsened over time (0.5 at 3 weeks to 0.3 at 10 weeks;~19% change). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 56 61 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. The exception was Y955C (Figure 5a) where LV dysfunction and LV dilation occurred early and persisted to 10 weeks. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 18 23 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. This resembled findings in I212N TGs in which increased mtDNA density at 10 weeks persisted (P<0.001). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV I212N 27 32 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Unlike the increase in mtDNA that resulted in TK2 native and mutant TGs, Y955C TGs consistently demonstrated significantly decreased mtDNA abundance in myocardial extracts (<50%, P<0.05) compared to WTs at both 3 and 10 weeks (Figure 3a and b). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 73 78 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Vehicle- and AZT-HAART-treated Y955C TGs each exhibited decreased mtDNA density (63-79%). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 31 36 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Vehicle-treated TK2 TGs (native TK2, and H121N or I212N mutants) exhibited mitochondria of normal size with essentially no detectable changes when compared to WTs (Figure 6a). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV H121N;I212N 41;50 46;55 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Vehicle-treated Y955C TGs exhibited increased mitochondrial number, irregular shape, and sparse fragmented cristae (Figure 6a). 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 16 21 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Y955C TG cardiac mtDNA density decreased further (P<0.001) at 10 weeks. 2009 Laboratory investigation; a journal of technical methods and pathology Result HIV Y955C 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. Among infants diagnosed in the first six weeks of life, the predominant mutations detected by standard population sequencing in SWEN and SD-NVP groups were Y181C (41% of 17 vs. 2009 PloS one Result HIV Y181C 156 161 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. In the event of late-breastfeeding transmission, Y188C/H was the most common mutation present and was found at similar frequencies for infants in the SWEN and SD-NVP groups (50% of 4 vs. 2009 PloS one Result HIV Y188C;Y188H 49;49 56;56 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. K103N was the most common mutation in three of these four women (75%; Table 3). 2009 PloS one Result HIV K103N 0 5 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. 4c) was prepared for this purpose and titrated by both the wt and the Asp366Asn mutated LEDGF IBD protein ligands. 2009 PloS one Result HIV D366N 70 79 Asp 70 73 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. The bi-helix motif we focus on (alpha4 helix-turn-alpha5 helix) occurs in the peptide segment from Gly-149 to Lys-186 of the IN-Phe185Lys variant. 2009 PloS one Result HIV F185K;I185K;N185K 128;128;128 137;137;137 IN 125 127 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Again, our results clearly demonstrate that the Q148H mutant was more strongly affected than other mutants, as shown by the significant decrease in the amount of integrated DNA forms and the simultaneous accumulation of 2-LTR circles. 2009 Nucleic acids research Result HIV Q148H 48 53 LTR 222 225 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Consistent with the quantification results obtained for the different DNA forms (Figure 3), only the production of p24 by the WT in the presence of RAL and by the Q148H mutant was severely impaired (p24 production decreased by 25- and 6-fold, respectively) (Figure 4). 2009 Nucleic acids research Result HIV Q148H 163 168 p24;p24 115;199 118;202 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Figure 4 also confirms the resistance of G140S/Q148H as shown by the limited effect of RAL on the p24 production of the double mutant. 2009 Nucleic acids research Result HIV G140S;Q148H 41;47 46;52 p24 98 101 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. G140S and E92Q mutants had slightly higher IC50 values (30 nM) than the WT. 2009 Nucleic acids research Result HIV E92Q;G140S 10;0 14;5 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. G140S rescues the catalytic defect due to the Q148H mutation. 2009 Nucleic acids research Result HIV Q148H;G140S 46;0 51;5 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. However, the Q148H and G140S mutations significantly decreased viral infectivity (3-fold and 2-fold less beta-galactosidase expression for Q148H and G140S, respectively, as compared with the WT level), probably because of a defect in the integration process. 2009 Nucleic acids research Result HIV G140S;G140S;Q148H;Q148H 23;149;13;139 28;154;18;144 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In contrast to G140S and G140S/Q148H, the single mutant Q148H appears to be more severely impaired than the other mutants, with a 3'-processing activity increasing only slightly to 35%, after up to 50 h of incubation, with concomitant decrease in the yield of strand transfer (Figure 5C). 2009 Nucleic acids research Result HIV G140S;G140S;Q148H;Q148H 15;25;31;56 20;30;36;61 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In fact, after normalization by the 3'-processing activity, we found that the strand transfer efficiency was 6.5%, 2.2% and 5.5% for WT, Q148H and G140S/Q148H mutants, respectively (Figure 5C). 2009 Nucleic acids research Result HIV G140S;Q148H;Q148H 147;137;153 152;142;158 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In parallel, we also obtained recombinant proteins encoding the entire IN sequence, as found in patients with the double G140S/Q148H mutation. 2009 Nucleic acids research Result HIV G140S;Q148H 121;127 126;132 IN 71 73 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In sharp contrast, RAL had only a slight effect on the DNA synthesis of the G140S/Q148H mutant (DNA synthesis was reduced by 1.2-fold at 64 h after infection), confirming the strong resistance of this double mutant. 2009 Nucleic acids research Result HIV G140S;Q148H 76;82 81;87 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In sharp contrast, the N155H, Q148H and G140S/Q148H mutants had much higher IC50 values, at 130, 450 and >1000 nM, respectively. 2009 Nucleic acids research Result HIV G140S;N155H;Q148H;Q148H 40;23;30;46 45;28;35;51 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Interestingly, the combination of these two mutations in the same virus resulted in levels of viral infectivity similar to those of the WT and much higher than obtained with the Q148H and G140S single mutations. 2009 Nucleic acids research Result HIV G140S;Q148H 188;178 193;183 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Interestingly, the kinetics of processing for the G140S and G140S/Q148H, although delayed in time as compared to the WT (t1/2 = 20.8 h for mutants, t1/2 = 4.1 h for WT), showed that these two mutants were able to reach WT levels of activity (Figure 5C). 2009 Nucleic acids research Result HIV G140S;G140S;Q148H 50;60;66 55;65;71 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Interestingly, two other mutations of the catalytic loop (G149A and G149A/G140A) display similar post DNA-binding defects. 2009 Nucleic acids research Result HIV G140A;G149A;G149A 74;58;68 79;64;73 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. It is important to note that both proteins, WT and G140S/Q148H, in the patient background displayed stronger activity than INs in the NL-43 context. 2009 Nucleic acids research Result HIV G140S;Q148H 51;57 56;62 IN 123 126 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Moreover, Figure 3B clearly shows the better fitness of G140S/Q148H in comparison to the single-mutant Q148H. 2009 Nucleic acids research Result HIV G140S;Q148H;Q148H 56;62;103 61;67;108 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Moreover, quantification of the product of the strand transfer reaction indicated that, under conditions in which the 3'-processing levels of the G140S/Q148H reached the WT levels, the yields of strand transfer are similar for the WT and the double mutant. 2009 Nucleic acids research Result HIV G140S;Q148H 146;152 151;157 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. N155H or E92Q or G140S/Q148H) into a WT pNL43 background. 2009 Nucleic acids research Result HIV E92Q;G140S;Q148H;N155H 9;17;23;0 13;22;28;5 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Our activity data after 3 h of incubation highlight some discrepancies between in vitro and ex vivo results, particularly for the G140S/Q148H double mutant virus, which replicated as well as the WT virus, despite the lower activity of the corresponding recombinant IN. 2009 Nucleic acids research Result HIV G140S;Q148H 130;136 135;141 IN 265 267 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. qPCR quantification showed the kinetics of total viral DNA accumulation to be similar for the WT and all mutants, with the exception of the Q148H virus, for which smaller amount of viral DNA were detected. 2009 Nucleic acids research Result HIV Q148H 140 145 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Remarkably, RAL had only a small effect on the levels of 2-LTR circles and integrated forms with the G140S/Q148H double mutant (Figure 3E). 2009 Nucleic acids research Result HIV G140S;Q148H 101;107 106;112 LTR 59 62 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The apparent discrepancy between beta-Gal assays and integration quantification of the G140S mutant will be further discuss in the next section. 2009 Nucleic acids research Result HIV G140S 87 92 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The effect of the Q148H mutation which strongly impairs this transition is reversed by adding the G140S mutation. 2009 Nucleic acids research Result HIV G140S;Q148H 98;18 103;23 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The G140S/Q148H double mutation is one of the main profiles identified in patients resistant to RAL. 2009 Nucleic acids research Result HIV G140S;Q148H 4;10 9;15 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The two single mutations, N155H and E92Q, neither disrupt the early steps of replication nor expression of integrated DNA, as shown by the corresponding beta-galactosidase levels, which were similar to the WT. 2009 Nucleic acids research Result HIV E92Q;N155H 36;26 40;31 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Thus, IN mutations have no crucial consequences for the dynamics of viral replication, except the for the Q148H mutant, which displayed high levels of 2-LTR circle accumulation related to an integration defect. 2009 Nucleic acids research Result HIV Q148H 106 111 LTR;IN 153;6 156;8 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Two main profiles were identified, one based on the N155H mutation and the other based on the G140S/Q148H mutations, which seemed to be present together in most cases. 2009 Nucleic acids research Result HIV G140S;N155H;Q148H 94;52;100 99;57;105 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Two other constructs with single G140S or Q148H mutations were analyzed in parallel. 2009 Nucleic acids research Result HIV G140S;Q148H 33;42 38;47 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Under the same conditions, the activities of the Q148H, G140S and G140S/Q148H were severely impaired, with the degree of impairment as follows: Q148H < < G140S/Q148H G140S < WT (Figure 5). 2009 Nucleic acids research Result HIV G140S;G140S;G140S;G140S;Q148H;Q148H;Q148H;Q148H 56;66;154;168;49;72;144;160 61;71;159;173;54;77;149;165 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Viral DNA synthesis levels were similar in the presence and absence of RAL for both the WT and the G140S/Q148H mutant (Figure 3A), confirming the absence of RAL effect on the reverse transcription step. 2009 Nucleic acids research Result HIV G140S;Q148H 99;105 104;110 RT 175 196 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We investigated the role of the G140 and Q148 residues in the resistance, by producing recombinant INs harboring either the G140S or the Q148H mutation, and the G140S/Q148H double mutant. 2009 Nucleic acids research Result HIV G140S;G140S;Q148H;Q148H 124;161;137;167 129;166;142;172 IN 99 102 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We performed the same experiment for the WT and the G140S/Q148H mutant in the presence of 500 nM RAL (a concentration 50 times higher than the IC50 value for the WT). 2009 Nucleic acids research Result HIV G140S;Q148H 52;58 57;63 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We then studied the effect of the Q148H and/or G140S mutations on 3'-processing and strand transfer activities using recombinant proteins. 2009 Nucleic acids research Result HIV G140S;Q148H 47;34 52;39 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Despite having K103N mutations detected before treatment, 7 women (36.8%) attained and sustained viral suppression; 1 was lost to follow-up. 2009 Clinical infectious diseases Result HIV K103N 15 20 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Detection of K103N mutations by AS-PCR before treatment was a strong predictor of inadequate virologic response (table 4). 2009 Clinical infectious diseases Result HIV K103N 13 18 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Eleven (57.9%) of 19 women who were either exposed or unexposed to sdNVP and who had K103N mutations detected by AS-PCR in either viral DNA or RNA had inadequate virologic response; 3 did not experience viral suppression (viral load, <50 copies/mL), and 8 experienced initial suppression followed by rebound (viral load, >400 copies/mL). 2009 Clinical infectious diseases Result HIV K103N 85 90 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. K103N mutations were also detected by AS-PCR in 9 (15.0%) of 60 sdNVP-unexposed women before treatment; they were detected in viral RNA for 8 women (13.3%) and in viral DNA for 3 women (5.0%). 2009 Clinical infectious diseases Result HIV K103N 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. K103N mutations were detected by AS-PCR in 10 (10.6%) of 94 sdNVP-exposed women before they commenced treatment; the mutations were detected in viral RNA for 10 women (10.6%) and in viral DNA for 3 women (3.2%). 2009 Clinical infectious diseases Result HIV K103N 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Of all 30 women who experienced an inadequate virologic response, 11 (36.7%) had K103N mutations detected before the commencement of treatment, and only 1 woman (3.3%), who had been exposed to sdNVP, had another major NNRTI-related mutation (Y181C) detected before treatment (table 5). 2009 Clinical infectious diseases Result HIV K103N;Y181C 81;242 86;247 NNRTI 218 223 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Poor adherence determined at the time of viral rebound or at the last visit if viral suppression occurred was significantly associated with inadequate viral response (42.1% of such women had poor adherence), compared with sustained viral suppression (20.9% of such women had poor adherence), among women who did not have K103N mutations detected before the commencement of treatment (P = .046). 2009 Clinical infectious diseases Result HIV K103N 321 326 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Samples with the highest percentages of K103N mutations detected by AS-PCR also had K103N mutations detected by population sequencing (table 3). 2009 Clinical infectious diseases Result HIV K103N;K103N 40;84 45;89 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. The association between pretreatment presence of the K103N mutation and inadequate virologic response remained after adjustment for viral load and CD4 cell count. 2009 Clinical infectious diseases Result HIV K103N 53 58 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. The cumulative probability of inadequate virologic response by week 78 was 0.609 among women with pretreatment K103N mutations and 0.151 among those without (P < .001). 2009 Clinical infectious diseases Result HIV K103N 111 116 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. The M184V mutation was more common among sdNVP-unexposed women than sdNVP-exposed women (9 of 12 vs. 2009 Clinical infectious diseases Result HIV M184V 4 9 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. There continued to be no association between sdNVP exposure and inadequate virologic response after adjustment for pretreatment viral load, CD4 cell count, and K103N mutation presence. 2009 Clinical infectious diseases Result HIV K103N 160 165 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. There was a nonsignificant association between the presence of the K103N mutation and lower CD4 cell counts and higher viral loads before treatment. 2009 Clinical infectious diseases Result HIV K103N 67 72 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Because patients in our cohort were exclusively treated with indinavir during the study, we focused on HIV-2 PR mutations K7R, I54M, V62A, I82F, L90M, and L99F, which have been associated with phenotypic PI resistance to indinavir in previous, albeit limited, studies. 2009 Clinical infectious diseases Result HIV I54M;I82F;K7R;L90M;L99F;V62A 127;139;122;145;155;133 131;143;125;149;159;137 PI;PR 204;109 206;111 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Eight of 23 patients had virus strains with PI mutations (K7R, I54M, V62A, I82F, L90M, and L99F) suggestive of indinavir resistance; 4 of these patients had virus strains that harbored multiple PI mutations (K7R-L99F, K7K/R/G-I54M-I82I/F, I82I/F-L99L/F, and V62A-L99F) (table 2). 2009 Clinical infectious diseases Result HIV I54M;I82F;I82F;I82I;I82I;K7G;K7K;K7R;L99F;L99L;I54M;I82F;K7R;K7R;L90M;L99F;L99F;L99F;V62A;V62A 226;231;239;231;239;218;218;218;246;246;63;75;58;208;81;91;212;263;69;258 230;237;245;237;245;225;225;225;252;252;67;79;61;211;85;95;216;267;73;262 PI;PI 44;194 46;196 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Five patients had virus strains with the M184V mutation at the initial genotyping at study entry, and 5 had virus strains that developed the mutation during the follow-up period. 2009 Clinical infectious diseases Result HIV M184V 41 46 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E) were not found, with the exception of K70R, which was present in a strain from 1 patient (in conjunction with K65R, Q151M, and 219E, the latter of which is commonly present in wild-type HIV-2 in ARV therapy naive patients). 2009 Clinical infectious diseases Result HIV D67N;K219E;K219Q;K65R;K70R;K70R;L210W;M41L;Q151M;T215F;T215Y 53;85;85;204;59;132;65;47;210;72;72 57;92;92;208;63;136;70;51;215;79;79 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. In HIV-1, the M184I mutation produces high-level in vitro resistance to 3TC and FTC and low-level resistance to didanosine and abacavir, has been reported in virus strains in both ARV therapy-naive and ARV-treated HIV-2-infected patients, and appears to be under selective pressure to 3TC in HIV-2 in vitro. 2009 Clinical infectious diseases Result HIV M184I 14 19 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Mutations K65R, Q151M, and M184V in RT have previously been shown to be associated with phenotypic NRTI resistance in HIV-2. 2009 Clinical infectious diseases Result HIV K65R;M184V;Q151M 10;27;16 14;32;21 NRTI;RT 99;36 103;38 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Naturally occurring HIV-2 PR polymorphisms that are associated with PI resistance in HIV-1 were common; major (V32I/L, M46I/V, and I47V) and minor (L10V/I, E35G/R, Q58E, A71V/I, and G73A/T) PI resistance mutations were found in all 23 patients. 2009 Clinical infectious diseases Result HIV A71I;A71V;E35G;E35R;G73A;G73T;I47V;L10I;L10V;M46I;M46V;Q58E;V32I;V32L 170;170;156;156;182;182;131;148;148;119;119;164;111;111 176;176;162;162;188;188;135;154;154;125;125;168;117;117 PI;PI;PR 68;190;26 70;192;28 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Of the 7 patients with multiclass drug-resistant virus, 3 had virus strains in which both NRTI and PI mutations emerged during the follow-up period, and 1 patient had a virus strains with RT M184V and PR I54M mutations at study entry that developed K7K/R/G and I82I/F mutations during the follow-up period. 2009 Clinical infectious diseases Result HIV I54M;I82F;I82I;K7G;K7K;K7R;M184V 204;261;261;249;249;249;191 208;267;267;256;256;256;196 NRTI;PI;PR;RT 90;99;201;188 94;101;203;190 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Polymorphisms of unclear significance for drug resistance in HIV-2 were also found in HIV-2 RT at known resistance codon positions: Q151I (in a strain from 1 patient) and Q151R (in a strain from 1 patient). 2009 Clinical infectious diseases Result HIV Q151I;Q151R 132;171 137;176 RT 92 94 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. reported the appearance of codon change Q151I (together with M41I and M184V) in an HIV-2 strain from a patient treated with AZT and 3TC who had virus with evidence of phenotypic resistance. 2009 Clinical infectious diseases Result HIV M184V;M41I;Q151I 70;61;40 75;65;45 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The canonical HIV-1 nonnucleoside reverse-transcriptase inhibitor mutations Y181I and Y188L were found in virus strains from all HIV-2- infected patients. 2009 Clinical infectious diseases Result HIV Y181I;Y188L 76;86 81;91 NNRTI 20 55 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The contribution of individual HIV-2 PR mutations that confer phenotypic resistance to PIs have not been delineated; however, the emergence of mutations (K7R, G17N, K45R, M46I, V47A, I54M, V62A, I64V, V71I, I82F/L, I84V, L90M, and L99F) in PR in HIV-2 from individuals receiving PI-based therapy have been observed in previous studies. 2009 Clinical infectious diseases Result HIV G17N;I54M;I64V;I82F;I82L;I84V;K45R;K7R;L90M;L99F;M46I;V47A;V62A;V71I 159;183;195;207;207;215;165;154;221;231;171;177;189;201 163;187;199;213;213;219;169;157;225;235;175;181;193;205 PI;PI;PR;PR 87;279;37;240 90;281;39;242 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The HIV-2 RT Q151M mutation, which confers multinucleoside resistance (to AZT, didanosine, stavudine, and FTC) was found in virus strains from 2 (9%) of 23 patients (both mutations were present at study entry). 2009 Clinical infectious diseases Result HIV Q151M 13 18 RT 10 12 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The M184I mutation (together with M184V) emerged in a virus strain from 1 patient. 2009 Clinical infectious diseases Result HIV M184I;M184V 4;34 9;39 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The RT K65R mutation, which confers resistance to 3TC, FTC, and didanosine, was also found in strains from 2 patients (1 patient also had virus with the Q151M mutation, and both mutations were present at study entry; the other patients had virus with a mixed K65K/R population emerge during the follow-up period). 2009 Clinical infectious diseases Result HIV K65K;K65R;K65R;Q151M 259;259;7;153 265;265;11;158 RT 4 6 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The RT mutation M184V, which confers high-level resistance to 3TC and emtricitabine (FTC) in HIV-2, was found in 10 (43%) of 23 patients (table 2). 2009 Clinical infectious diseases Result HIV M184V 16 21 RT 4 6 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The V111I polymorphism, which is commonly found in RT in strains in ARV therapy-naive patients but has been reported to be associated with the Q151M resistance mutation, was found in virus strains from both patients with Q151M mutations (patients H2A2 and H2A24), in a strain from 1 patient with only an M184V mutation (patient H2A15), and in a strain from 1 patient with no RT mutations (wild-type; patient H2A5). 2009 Clinical infectious diseases Result HIV M184V;Q151M;Q151M;V111I 304;143;221;4 309;148;226;9 RT;RT 51;375 53;377 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Two patients who were married (patients H2A14 and H2A25) were infected with closely linked strains, although only 1 partner was infected with virus with evidence of ARV resistance (M184M/V mutation) (figure 2). 2009 Clinical infectious diseases Result HIV M184M;M184V 181;181 189;189 19149765 Analysis and characterization of dimerization inhibition of a multi-drug-resistant human immunodeficiency virus type 1 protease using a novel size-exclusion chromatographic approach. PRMDR contains multiple drug-resistant mutations (L10I, K45R, I54V, L63P, A71V, V82T, L90M and I93L) and is highly resistant to a number of active-site inhibitors, although it remains sensitive to the experimental active-site inhibitor JE-2147. 2009 The Biochemical journal Result HIV A71V;I54V;I93L;K45R;L10I;L63P;L90M;V82T 74;62;95;56;50;68;86;80 78;66;99;60;54;72;90;84 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. also observed that HIV capsid assembly is abolished when the sole Trp184 is mutated to Ala. 2009 Biomacromolecules Result HIV W184A 66 90 Capsid 23 29 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Consistent with the rmsd analysis, W184A mutant also displayed the largest residue-based root-mean-square fluctuation (RMSF) as compared to the wild-type (Figure 2b), in which the RMSF was used to assess the local dynamical variation of each individual residue. 2009 Biomacromolecules Result HIV W184A 35 40 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Figure 2 shows the backbone root-mean-square deviation (RMSD) for the wild-type (146-231) and mutants W184A and M185A. 2009 Biomacromolecules Result HIV M185A;W184A 112;102 117;107 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Figures 6a-c show the intermolecular distances of four identical residue pairs at the dimeric interface between E180I-E180II, Q192I-Q192II, W184I-W184II, or A184I-A184II, and M185I-M185II or A185I-A185II, where I and II represent different monomeric CTDs. 2009 Biomacromolecules Result HIV A184I;A185I;E180I;M185I;Q192I;W184I 163;197;118;175;126;140 168;202;123;180;131;145 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Gamble and co-workers found that Q155N and E159D mutants can block HIV-1 replication, indicating that the distinct motifs in the CA could perform the same function. 2009 Biomacromolecules Result HIV E159D;Q155N 43;33 48;38 Capsid 129 131 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Impact of Mutations at the Helix 2 Region (W184A and M185A) on the Structure and Dynamics of the CA Dimer. 2009 Biomacromolecules Result HIV M185A;W184A 53;43 58;49 Capsid 97 99 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Impact of Mutations at the MHR Region (Q155N and E159D) on the Structure and Dynamics of the CA Dimer. 2009 Biomacromolecules Result HIV E159D;Q155N 49;39 54;45 Capsid 93 95 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. In contrast, for the mutant W184A, all four residue-pair distances experienced large fluctuations, quickly increasing within the first 10 ns, which indicated that they lost their original contacts at the helix2I-helix2II interface (Figure 6b). 2009 Biomacromolecules Result HIV W184A 28 33 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. In contrast, the M185A substitution caused no gross perturbation of the whole dimeric structure, only subtle changes in the interaction sites (Figure 3c). 2009 Biomacromolecules Result HIV M185A 17 22 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Interestingly, although Glu159 is far from the interface between the MHR and helix 2 motifs and does not interact with Ala194 and Asn195, a replacement of Glu159 with Asp is likely to allosterically perturb interactions near the turn region, with the bent turn shifting slightly away from the MHR-helix2 interface. 2009 Biomacromolecules Result HIV E159D 155 170 Asp 167 170 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Interestingly, although residue Glu159 is far from the helix 2 region and is not involved in any contact with residues in the helix 2, E159D also led to the loss of two hydrogen bonds and potential van der Waals interactions within the MHR region (Figure 4c). 2009 Biomacromolecules Result HIV E159D 135 140 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Interestingly, although the W184A mutant tended to disrupt the dimeric interface, it imposes a little influence on the local secondary structures since all helices were still well preserved during the simulations. 2009 Biomacromolecules Result HIV W184A 28 33 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. It is reasonable to expect that substitutions at positions of 155 and 159, other than Q155N and E159D, will lead to even larger structural perturbation in the loop due to the large differences of molecular size and hydrophobicity of sidechains. 2009 Biomacromolecules Result HIV E159D;Q155N 96;86 101;91 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. It should be noted that in the M185A mutant, Trp184 still dominated a large number of interactions with Val181, Thr188, and Leu189 at the dimeric interface of the M185A. 2009 Biomacromolecules Result HIV M185A;M185A 31;163 36;168 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. M185A displayed some distance fluctuation between Q192I-Q192II, but no significant difference was observed between the wild-type and the mutant M185A (Figure 6c), primarily due to that short Met185 did not involve many interactions with its neighboring residues. 2009 Biomacromolecules Result HIV M185A;Q192I;M185A 144;56;0 149;61;5 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. reported that the binding affinity of a capsid assembly inhibitor (CAI) for the M185A mutant was reduced but not completely abolished in ELISAs. 2009 Biomacromolecules Result HIV M185A 80 85 Capsid 40 46 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Similar allosteric effects on the HIV-1 protease flap that is a target for drug design have also been observed.- Substitutions of conserved Gln155 by Asn and Glu159 by Asp only result in subtle changes in the initial structures at the MHR because Gln vs Asn and Glu vs Asp have similar molecular size and hydrophobicity; thus, it is expected that these mutations would neither introduce large new interactions, nor alter backbone conformation. 2009 Biomacromolecules Result HIV E159D;Q155N 158;140 171;153 PR;Asp;Asp 40;168;269 48;171;272 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The average interaction energies for the last 20 ns were -131.8 +- 10.2, -87.9 +- 9.1, -85.4 +- 7.3, -90.9 +- 10.2, -62.3 +- 14.0, and -63.5 +- 8.4 cal/mol for the wild-type (146-231), wild-type (151-231), W184A, M185A, Q155N, and E159D, respectively (Table 2 and Figure 8). 2009 Biomacromolecules Result HIV E159D;M185A;Q155N;W184A 231;213;220;206 236;218;225;211 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The loss of hydrogen bonding and side chain contacts between the MHR and helix 2 regions strongly affects the structural fluctuation of the local turn region (residues 155-159), as indicated by RMSF values rising from 1.81 A (wild-type) to 4.47 A (Q155N; Figure 4b). 2009 Biomacromolecules Result HIV Q155N 248 253 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The Q155N mutant quickly lost interactions with Asn195 and Ala194 at the helix 2 region, as indicated by the continuous increase in pairwise residue distances; however, the interactions between Asn155 and Glu159 were well conserved (Figure 6e). 2009 Biomacromolecules Result HIV Q155N 4 9 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The Q155N substitution significantly disrupted the hydrogen-bond network of residue 155 with Ala194, Asn195, and Glu159, decreasing from nine (wild-type) to three (Q155N; Figure 5b). 2009 Biomacromolecules Result HIV Q155N;Q155N 4;164 9;169 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The RMSDs of both the wild-type and M185A mutant were maintained at 2.8 and 3.1 A for 20 ns, respectively (Figure 2a and Table 1), indicating that (i) both sequences were considerably stable and (ii) replacement of Met185 with Ala has a little influence on the overall stability of dimeric CTDs. 2009 Biomacromolecules Result HIV M185A;M185A 36;215 41;230 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The wild-type (146-231) has the most favorable, lowest interaction energy consistent with previous structural analysis, whereas the Q155N and E159D mutants have comparable unfavorable free energies. 2009 Biomacromolecules Result HIV E159D;Q155N 142;132 147;137 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. There was no apparent difference in the RMSF between the wild-type and the M185A mutant. 2009 Biomacromolecules Result HIV M185A 75 80 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. These results suggest that the most critical interaction at the dimeric interaction is W184I-W184II; whereas M185I-M185II interaction has little effect on stabilization of the dimer interface. 2009 Biomacromolecules Result HIV M185I;W184I 115;93 120;98 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Unlike Trp184, structural analysis of M185A does not show a significant difference from the wild-type 146-231, but the binding free energy of the dimeric complex lost ~40.9 kcal/mol as compared to the wild-type, implying that some interactions could be lost upon the mutation. 2009 Biomacromolecules Result HIV M185A 38 43 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. When the large Trp was replaced by the Ala at position 184, the smaller residue can not attain sufficient packing interactions with its neighboring residues, leading to the increase of the structural flexibility of the dimeric interface due to the loss of interactions. 2009 Biomacromolecules Result HIV W184A 15 58 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. 2E show that release from the pausing site at position +5 was compromised with K65R RT, while the K65R+M184V RT was severely impaired in release from the +3 pausing site. 2009 Retrovirology Result HIV K65R;K65R;M184V 79;98;103 83;102;108 RT;RT 84;109 86;111 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. 4B) terminated primers, the subtype C WT RT mutants K65R and K65R+M184V RT showed impaired excision efficiency compared with WT. 2009 Retrovirology Result HIV K65R;K65R;M184V 52;61;66 56;65;71 RT;RT 41;72 43;74 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. All mutant enzymes were significantly impaired in specific activity compared with wild-type enzyme, with K65R exhibiting only 46%-50% of wild-type activity and K65R+M184V RT exhibiting only 30% of wild-type activity. 2009 Retrovirology Result HIV K65R;K65R;M184V 105;160;165 109;164;170 RT 171 173 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. As a result, the order of susceptibility of subtype C RTs to TFV-DP was WT > K65R+M184V > K65R. 2009 Retrovirology Result HIV K65R;K65R;M184V 77;90;82 81;94;87 RT 54 57 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. As dNTP concentration decreased, K65R RT showed less extension than WT enzyme; the difference was more pronounced in reactions with the lowest dNTP concentration. 2009 Retrovirology Result HIV K65R 33 37 RT 38 40 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. At high dNTP concentration (200 muM), K65R RT showed similar activity as WT, while the double mutant K65R+M184V RT was impaired in primer extension. 2009 Retrovirology Result HIV K65R;K65R;M184V 38;101;106 42;105;111 RT;RT 43;112 45;114 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. ATP-mediated excision of TFV-or ZDV-terminated primer was decreased by 2.6-and 3.1-fold for K65R and K65R+M184V RTs, respectively (TFV 23%, ZDV 15% at 30 min) compared to WT RT (TFV 60%, ZDV 47% at 30 min). 2009 Retrovirology Result HIV K65R;K65R;M184V 92;101;106 96;105;111 RT;RT 112;174 115;176 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Calculations of IC50s for TFV-DP showed that subtype C K65R RT displayed a 9.8-fold decreased susceptibility to TFV-DP compared with WT RT. 2009 Retrovirology Result HIV K65R 55 59 RT;RT 60;136 62;138 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. For the double mutant K65R/M184V, the Km value for dATP was significantly increased compared to that of WT (P <= 0.01) and the Ki value for TFV-DP was also increased compared to WT (P <= 0.01). 2009 Retrovirology Result HIV K65R;M184V 22;27 26;32 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. However, the Ki value of K65R RT for TFV-DP was significantly increased compared to that of WT (P <= 0.01). 2009 Retrovirology Result HIV K65R 25 29 RT 30 32 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In cell culture assays, subtype C K65R viruses, like subtype B K65R viruses, exhibited lower replication capacity and addition of M184V enhanced this effect. 2009 Retrovirology Result HIV K65R;K65R;M184V 34;63;130 38;67;135 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In our cell-free assay with subtype C RTs harbouring K65R and K65R/M184V, we also observed impaired efficiency of (-)ssDNA synthesis; the decrease in product formation was most pronounced at earlier time points. 2009 Retrovirology Result HIV K65R;K65R;M184V 53;62;67 57;66;72 RT 38 41 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In pilot time-course experiments, we also performed reactions at high dNTP concentration (100 muM-200 muM), and observed that the double mutant enzyme showed reduced efficiency in ssDNA synthesis; in contrast K65R RT showed similar efficiency as WT (data not shown). 2009 Retrovirology Result HIV K65R 209 213 RT 214 216 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In this study, we determined the efficiencies of incorporation of TFV-DP using subtype C WT and mutant K65R and K65R+M184V RTs in gel-based assays using the 19D/57D primer/template system. 2009 Retrovirology Result HIV K65R;K65R;M184V 103;112;117 107;116;122 RT 123 126 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Mutant K65R/M184V RT displayed maximal decrease in product formation and accumulation at the +3 and +5 pausing sites. 2009 Retrovirology Result HIV K65R;M184V 7;12 11;17 RT 18 20 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Previous cell culture assays showed that viruses of subtypes A/E, B, C harboring K65R exhibited similar 6.5 to 10-fold resistance to TFV. 2009 Retrovirology Result HIV K65R 81 85 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Similar results were obtained with subtype B RT WT and K65R and K65R+M184V mutant RTs (data not shown). 2009 Retrovirology Result HIV K65R;K65R;M184V 55;64;69 59;68;74 RT;RT 45;82 47;85 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The observation of diminished activity associated with K65R mutant RTs of both subtypes is in agreement with results obtained previously with subtype B K65R RT. 2009 Retrovirology Result HIV K65R;K65R 55;152 59;156 RT;RT 67;157 70;159 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The order of efficiency of (-)ssDNA synthesis was WT > K65R >> K65R+M184V. 2009 Retrovirology Result HIV K65R;K65R;M184V 55;63;68 59;67;73 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The reduced efficiency of initiation of (-)ssDNA synthesis and tRNA primer usage, associated with subtype B RTs harboring K65R and K65R+M184V is a mechanism responsible for the diminished replicative fitness of viruses containing these substitutions (Fig 2A). 2009 Retrovirology Result HIV K65R;K65R;M184V 122;131;136 126;135;141 RT 108 111 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The simultaneous presence of K65R and M184V resensitized these enzymes for TFV-DP by 5-fold compared to WT RT. 2009 Retrovirology Result HIV K65R;M184V 29;38 33;43 RT 107 109 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The steady state Km value of K65R RT for dATP was slightly elevated (0.51 muM to 0.64 muM) compared to WT RT, suggesting that subtype C K65R RT binds to and incorporates the natural dATP substrate with an efficiency similar to or slightly reduced to that of WT RT. 2009 Retrovirology Result HIV K65R;K65R 29;136 33;140 RT;RT;RT;RT 34;106;141;261 36;108;143;263 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. To determine the effects of mutations K65R and K65R+M184V in subtype C RTs on TFV-binding and incorporation, we measured the steady-state kinetic constant Km for dATP and inhibition constant Ki for TFV-DP (Table 1). 2009 Retrovirology Result HIV K65R;K65R;M184V 38;47;52 42;51;57 RT 71 74 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. A second group, formed by P51G-m4-CVN and CVNMutDB, can only form one interaction with gp120 per molecule. 2009 Biopolymers Result HIV P51G 26 30 gp120 87 92 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Additional S52P or DeltaQ50 mutations to m4-CVN further destabilize the protein to 39.5 C and 32.5 C, respectively. 2009 Biopolymers Result HIV S52P 11 15 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Binding of S52P-m4-CVN and DeltaQ50-m4-CVN to its viral target, gp120, was measured in an ELISA experiment (see Figure 3). 2009 Biopolymers Result HIV S52P 11 15 gp120 64 69 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Co-injection experiments with monomeric and dimeric wt CV-N, separated by gel filtration chromatography, demonstrated that S52P-m4-CVN and DeltaQ50-m4-CVN coeluted with the dimeric form of wt CV-N, and are distinct from the monomeric form (data not shown). 2009 Biopolymers Result HIV S52P 123 127 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Each contains a single carbohydrate-binding domain (B and A, respectively) and the P51G mutation in the hinge region, resulting in a higher barrier for conversion to dimer. 2009 Biopolymers Result HIV P51G 83 87 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. For comparison, monomeric P51G-m4-CVN is completely inactive at the concentration range tested (0.01 nM-1 muM); note that loss of activity was observed at concentrations higher than those conducive to binding of gp120. 2009 Biopolymers Result HIV P51G 26 30 gp120 212 217 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. However, one should keep in mind that DeltaQ50-m4-CVN and S52P-m4-CVN exhibit thermal unfolding profiles with midpoints close to 38 C. 2009 Biopolymers Result HIV S52P 58 62 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. In contrast, mutating a proline in the hinge region to glycine results in monomers, as seen in P51G-m4-CVN and [P51G]CV-N. 2009 Biopolymers Result HIV P51G;P51G 95;112 99;116 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Mutations in the hinge region and in domain A are additive, resulting in a significant destabilization of S52P-m4-CVN and DeltaQ50-m4-CVN compared to wt CV-N. 2009 Biopolymers Result HIV S52P 106 110 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Note that P51G-m4-CVN and CVNMutDB contain different intact domains (B and A, respectively), yet display similar impairment of function. 2009 Biopolymers Result HIV P51G 10 14 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. On the basis of the evidence presented here, we concluded that the hinge region mutations S52P and DeltaQ50 affect the oligomerization state consistently on the background of wt CV-N and on m4-CVN, resulting in the formation of domain-swapped dimers. 2009 Biopolymers Result HIV S52P 90 94 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. S52P-m4-CVN and DeltaQ50-m4-CVN are Dimers in Solution. 2009 Biopolymers Result HIV S52P 0 4 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The binding observed differs between two groups of CV-N analogs: a first group, comprising wt CV-N, m4-CVN, and dimeric P51G-m4-CVN, which can form multidentate inter actions with gp120 through different mechanisms, bind gp120 with subnanomolar EC50. 2009 Biopolymers Result HIV P51G 120 124 gp120;gp120 180;221 185;226 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The circular dichroism (CD) spectra of S52P-m4-CVN and DeltaQ50-m4-CVN each display a minimum at 206 nm and maximum at 192 nm. 2009 Biopolymers Result HIV S52P 39 43 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The domain-swapped form of CV-N, which is a metastable state in wild type, is stabilized relative to the monomer by mutations S52P and DeltaQ50: hinge region mutants S52P-CVN and DeltaQ50-CVN result in the formation of obligate domain-swapped dimers, as verified by NMR. 2009 Biopolymers Result HIV S52P;S52P 126;166 130;170 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The extent of destabilization observed follows the same trend observed for S52P and AQ50 on the background of wt CV-N, with DeltaTms of ~ -7 C and -11 C, respectively. 2009 Biopolymers Result HIV S52P 75 79 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The oligomerization states of recombinant S52P-m4-CVN and DeltaQ50-m4-CVN in solution were evaluated by size-exclusion chromatography. 2009 Biopolymers Result HIV S52P 42 46 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. The results obtained for S52P-m4-CVN and DeltaQ50-m4-CVN are intermittent between these two groups, suggesting a multivalent effect. 2009 Biopolymers Result HIV S52P 25 29 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. These mutants bind gp120 with much higher EC50, reflecting weaker interactions (~ 180 nM for P51G-m4-CVN, above 1 muM for CVNMutDB). 2009 Biopolymers Result HIV P51G 93 97 gp120 19 24 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Thus, the difference in activity relative to wt CV-N could be due to partial unfolding of DeltaQ50-m4-CVN and S52P-m4-CVN in the conditions of the experiments. 2009 Biopolymers Result HIV S52P 110 114 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. We introduced S52P and DeltaQ50 on m4-CVN to restore multivalency to the construct. 2009 Biopolymers Result HIV S52P 14 18 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Weak activity was observed at the highest concentration tested (1 muM) for S52P-m4-CVN, but the EC50 value could not be determined. 2009 Biopolymers Result HIV S52P 75 79 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. However, none of the 104 samples had a mutation pattern predictive of reduced protease inhibitor susceptibility, and only three samples had a mutation used for genotypic surveillance of transmitted protease inhibitor drug resistance: one subtype A sample had I47V, one subtype D sample had F53L, and one subtype A1 sample had N88D. 2009 AIDS (London, England) Result HIV F53L;I47V;N88D 290;259;326 294;263;330 PR;PR 78;198 86;206 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. Seven of the 104 samples (6.7%) had a mutation associated with NRTI resistance (one mutation in each sample: M41L (n = 2), E44D (n = 3), V118V/I (n = 1), K219K/R (n = 1)), and one sample had a mutation associated with NNRTI resistance (E138A). 2009 AIDS (London, England) Result HIV E138A;E44D;K219K;K219R;M41L;V118I;V118V 236;123;154;154;109;137;137 241;127;161;161;113;144;144 NNRTI;NRTI 218;63 223;67 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. The mutations M41L (detected in two subtype D samples) and K219K/R (detected in one subtype A1 sample) were the only mutations identified that are among those used for genotypic surveillance of transmitted NRTI drug resistance. 2009 AIDS (London, England) Result HIV K219K;K219R;M41L 59;59;14 66;66;18 NRTI 206 210 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Although exclusion of codon 101 from the analysis failed to show such linkage, M50_13B_K101E still remained at the base of the mother cluster, as one of the sequences from the mother most similar to the child cluster (Figure 2B). 2009 PloS one Result HIV K101E 87 92 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Among P50 sequences the mutations A98S, K101E, I135T and E138A were observed in all isolates. 2009 PloS one Result HIV A98S;E138A;I135T;K101E 34;57;47;40 38;62;52;45 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. In seven of these sequences the G190A mutation was present. 2009 PloS one Result HIV G190A 32 37 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. K101E was found in one sequence. 2009 PloS one Result HIV K101E 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. M50 sequences also showed mutations A98S, I135T and E138A. 2009 PloS one Result HIV A98S;E138A;I135T 36;52;42 40;57;47 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. NNRTI-resistant V106A and K103N variants were seen in two sequences, Y181C and Y188C in two sequences, and Y188H in five sequences. 2009 PloS one Result HIV K103N;V106A;Y181C;Y188C;Y188H 26;16;69;79;107 31;21;74;84;112 NNRTI 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. None of 344 NNRTI sensitive clones from M50 sequenced showed the K101E mutation. 2009 PloS one Result HIV K101E 65 70 NNRTI 12 17 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Other polymorphisms (L100I, L100S, V106A) were observed in individual sequences but were not associated with G190A mutation. 2009 PloS one Result HIV G190A;L100I;L100S;V106A 109;21;28;35 114;26;33;40 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Taken together, all phylogenetic evidences suggest that M50_13B_K101E, the only viral sequence from the mother carrying K101E, share common ancestry with viruses circulating in P50. 2009 PloS one Result HIV K101E;K101E 120;64 125;69 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The Bayesian MCMC analysis revealed that the cluster from the mother harboring sequence M50_13B_K101E was indeed more closely-related to the child cluster (Figure 3). 2009 PloS one Result HIV K101E 96 101 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The K101E-containing variant from the mother (M50_13B_K101E) showed phylogenetic evidence of common ancestry with the child cluster, as seen by the net formed by both clusters (Figure 2A). 2009 PloS one Result HIV K101E;K101E 4;54 9;59 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. ELISPOT assays for A*7401-positive patient samples confirmed two epitopes overlapping the region containing the positively selected residue S9N (Table 2). 2009 AIDS (London, England) Result HIV S9N 140 143 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. For example, four out of five samples tested recognized KIWPSSKGR (KR9c) or KLWPSNKGR (KR9s) containing I5L at anchor position 2, three of which responded to both peptides (Table 3a). 2009 AIDS (London, England) Result HIV I5L 104 107 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Further analysis of the positively selected amino acids at positions 5 and 7 of p1 showed that I5L was also significantly correlated with B*1302 (Ile Leu, P=0.0108), and P7S was significantly associated with A*30 (Pro Ser; P=0.009), suggesting that this region contains epitopes of multiple HLA alleles. 2009 AIDS (London, England) Result HIV I5L;P7S 95;170 98;173 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Our previous study identified four positively selected amino acid residues in the p1 spacer protein by Quasi analysis and two of the positively selected residues, K4R and S9N, were significantly correlated with B*1302 (Lys Arg, P=0.0008) and A*7401 (Ser Asp, P=0.0002), respectively. 2009 AIDS (London, England) Result HIV K4R;S9N 163;171 166;174 Asp 254 257 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Peptides LGKIWPSSK (LK9c) and LGKIWPSNK (LK9s) with the S9N mutation in anchor position 8 were tested with PBMCs from 14 patients. 2009 AIDS (London, England) Result HIV S9N 56 59 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Peptides RQANFLGKI (RI9c) and RQANFLGRI (RI9s) contain K4R at anchor residue 8. 2009 AIDS (London, England) Result HIV K4R 55 58 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Peptides WPSSKGRPG (WG9c) and WSSNKGRPG (WG9s) contain P7S in anchor position 2. 2009 AIDS (London, England) Result HIV P7S 55 58 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. The two types of epitopes can be seen among three B*1302 epitopes or six epitope variants overlapping the region with the positively selected residues K4R and I5L (Table 2). 2009 AIDS (London, England) Result HIV I5L;K4R 159;151 162;154 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Therefore, the peptide variants RQANFLGKI (RI9c) and RQANFLGRI (RI9s) belong to type I epitope, whereas peptides GKIWPSSKG (GG9c) and GRIWPSNKG (GG9s) with K4R at anchor position 2 represent the type II epitope. 2009 AIDS (London, England) Result HIV K4R 156 159 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Two epitopes for the A*30 group were identified by ELISPOT assays for the region containing the P7S mutation. 2009 AIDS (London, England) Result HIV P7S 96 99 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. A slightly different and less clear picture was seen with virus VIS18, where the IC50 effect of reversion of A431V was relatively modest, in particular with IDV, and where this effect did not seem to be quite as pronounced as that seen with the XS clone. 2009 PLoS pathogens Result HIV A431V 109 114 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. As seen in Figure 5, the reversion of mutations A431V or I437V in BS clones from patients VIS13 and VIS16 resulted in a strong decrease in the IC50 of the three PIs tested, corresponding to a loss of resistance. 2009 PLoS pathogens Result HIV A431V;I437V 48;57 53;62 PI 161 164 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Coherent with this observation, when mutations A431V and I437V were introduced in the XS clones, a strong increase in IC50 was seen, back to levels close to those seen with the BS clones. 2009 PLoS pathogens Result HIV A431V;I437V 47;57 52;62 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. For virus VIS13BS, which carried all patient-derived Gag sequences including mutation A431V, fully processed NC amounted to ~80% of all NC-reactive products in the presence of 0,5 microM LPV (Figure 7C). 2009 PLoS pathogens Result HIV A431V 86 91 Gag;NC;NC 53;109;136 56;111;138 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Having established that the determinants in Gag able to exert an enhancing effect on HIV-1 RC and resistance to PIs are essentially restricted to the NC-SP2-p6 region, we sought to evaluate the precise role of NC-SP2 mutations A431V and I437V in this phenomenon. 2009 PLoS pathogens Result HIV A431V;I437V 227;237 232;242 SP2;SP2;Gag;NC;NC;Gag;PI 153;213;44;150;210;157;112 156;216;47;152;212;159;115 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. In VIS13, reversion of A431V from VIS13BS reduced RC by about half, a reduction that was strikingly lower than that seen with VIS13XS. 2009 PLoS pathogens Result HIV A431V 23 28 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. In VIS16, the change in RC produced by reversion of I437V was again marginal, but in this virus, only a small change in RC was seen when comparing the BS and the XS clone. 2009 PLoS pathogens Result HIV I437V 52 57 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. In VIS18, the reversion of A431V from VIS18BS did not significantly change RC, contrasting with the strong reduction in RC seen in VIS18XS. 2009 PLoS pathogens Result HIV A431V 27 32 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Individual role of NC-SP2 cleavage site mutations A431V and I437V in the ability of patient-derived Gag sequences to enhance RC and resistance. 2009 PLoS pathogens Result HIV A431V;I437V 50;60 55;65 SP2;Gag;NC 22;100;19 25;103;21 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Interestingly, mutations A431V and I437V were found to be mutually exclusive in these 6 viruses, which was also the case in the 20 other patients of the ANRS 109 study (data not shown). 2009 PLoS pathogens Result HIV A431V;I437V 25;35 30;40 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Introducing the A431V mutation into this background reverted the NC/NC-SP2 ratio yielding a NC processing profile comparable to that of VIS13BS at all LPV concentrations. 2009 PLoS pathogens Result HIV A431V 16 21 SP2;NC;NC;NC 71;65;68;92 74;67;70;94 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Mutation A431V, at the P2' position of the NC-SP2 cleavage site was found in 4 viruses. 2009 PLoS pathogens Result HIV A431V 9 14 SP2;NC 46;43 49;45 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Mutation I437V, immediately downstream of that cleavage site, was found in 2 viruses, and mutation L449H, at the P1 position of the SP2-p6 cleavage site was found in one virus, in association with the A431V mutation. 2009 PLoS pathogens Result HIV A431V;I437V;L449H 201;9;99 206;14;104 SP2;Gag 132;136 135;138 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Nonetheless, introduction of A431V in VIS18XS produced a strong and significant increase in IC50 to all 3 tested drugs, to levels comparable to those seen with VIS18BS. 2009 PLoS pathogens Result HIV A431V 29 34 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Reversion of A431V in VIS13BS (clone VISBS431A) produced a clear change in this pattern with NC-SP2 amounting to ~65% of all NC-reactive species at 2,5 microM LPV (Figure 7C). 2009 PLoS pathogens Result HIV A431V 13 18 SP2;NC;NC 96;93;125 99;95;127 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. We therefore selected XS clones from 3 patients and introduced the A431V (seen in VIS13 and VIS18 viruses) or the I437V (seen in VIS16) mutations into the NL4-3-derived Gag sequences, yielding the VIS13XS431V, the VIS16XS437V and the VIS18XS431V mutants (Figure 4). 2009 PLoS pathogens Result HIV A431V;I437V 67;114 72;119 Gag 169 172 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. A sensitive, sequence-specific assay, LigAmp, was used to screen virus released after activation of resting CD4+ T cells for the presence of 3 major nevirapine resistance mutations: K103N, Y181C, and G190A (table 2). 2009 The Journal of infectious diseases Result HIV G190A;K103N;Y181C 200;182;189 205;187;194 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. For patient LT1020, LigAmp analysis indicated that virus isolated from the latent reservoir contained both the K103N and G190A resistance mutations (figure 3A). 2009 The Journal of infectious diseases Result HIV G190A;K103N 121;111 126;116 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. For resistant viruses that persisted in both compartments, it appears that the fitness cost of the K103N mutation was sufficiently low such that mutant viruses could continue to replicate over a prolonged period. 2009 The Journal of infectious diseases Result HIV K103N 99 104 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. Four clusters of viruses containing the K103N resistance mutation were revealed by phylogenetic analysis. 2009 The Journal of infectious diseases Result HIV K103N 40 45 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. In addition, a single viral clone containing the G190A resistance mutation was identified among viruses released from the latent reservoir. 2009 The Journal of infectious diseases Result HIV G190A 49 54 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. One K103N-containing viral sequence appears to be ancestral to all other viral sequences isolated from patient LT1020 (asterisk in figure 3B), indicating that this patient could have been infected by virus containing the K103N resistance mutation. 2009 The Journal of infectious diseases Result HIV K103N;K103N 4;221 9;226 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. One wild-type viral sequence clusters with a group of K103N-containing viral sequences, suggesting that it is a revertant sequence (located at the bottom of the phylogenetic tree). 2009 The Journal of infectious diseases Result HIV K103N 54 59 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. The K103N and G190A mutations were not present in the same viral genome, indicating that they arose independently in response to nevirapine. 2009 The Journal of infectious diseases Result HIV G190A;K103N 14;4 19;9 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. The K103N mutation was identified most frequently, followed by the G190A mutation. 2009 The Journal of infectious diseases Result HIV G190A;K103N 67;4 72;9 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. The same nevira-pine resistance mutation (K103N) identified in a previous analysis of plasma virus after single-dose nevirapine was identified among virus from the latent reservoir for 2 women in our study. 2009 The Journal of infectious diseases Result HIV K103N 42 47 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. The Y181C resistance mutation was not identified among any samples (table 3). 2009 The Journal of infectious diseases Result HIV Y181C 4 9 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. This wild-type viral sequence has 3 unique polymorphisms that distinguish it from the rest of the sequences in this clade, 1 of which resulted in the disappearance of the K103N mutation. 2009 The Journal of infectious diseases Result HIV K103N 171 176 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. Viruses containing the K103N resistance mutation were readily detected among viruses released from the latent reservoir and in plasma. 2009 The Journal of infectious diseases Result HIV K103N 23 28 19338474 Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1. Viruses with the K103N mutation composed 28% of the latent reservoir sequences analyzed and 23% of the plasma sequences analyzed. 2009 The Journal of infectious diseases Result HIV K103N 17 22 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. 3.1 +- 0.3 mumol/L, for Q151M and Q151M+3, respectively), indicating that A62V, F77L, and Y116F do not enhance AZT resistance in HIV-2. 2009 The Journal of infectious diseases Result HIV A62V;F77L;Q151M;Q151M;Y116F 74;80;24;34;90 78;84;29;39;95 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Although A62V, F77L, and Y116F increase the level of Q151M-mediated AZT resistance in HIV-1, the Q151M and Q151M+3 variants of HIV-2ROD exhibited comparable sensitivity to the drug (mean EC50 [+-SD], 5.2 +- 2.3 vs. 2009 The Journal of infectious diseases Result HIV A62V;F77L;Q151M;Q151M;Q151M;Y116F 9;15;53;97;107;25 13;19;58;102;112;30 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. As a result, the HIV-2ROD mutant that contained K65R, Q151M, and M184V showed >=40-fold resistance to AZT, ddI, 3TC, and FTC; >10-fold resistance to ABC; and 4-5-fold resistance to d4T and PMPA. 2009 The Journal of infectious diseases Result HIV K65R;M184V;Q151M 48;65;54 52;70;59 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. As observed for Q151M HIV-2ROD, the Q151M variant of HIV-2ROD/UC2 was highly resistant to AZT (a 30-fold increase in EC50, compared with that of WT HIV-2ROD-UC2; the mean EC50 values [+-SD] were 0.071 +- 0.2 and 2.1 +- 0.2 mumol/L for WT and Q151M HIV-2ROD/UC2, respectively). 2009 The Journal of infectious diseases Result HIV Q151M;Q151M;Q151M 16;36;242 21;41;247 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Finally, in the HIV-2ROD mutant that contained K65R, Q151M, and M184V we observed greater-than-additive increases in the levels of resistance to ddI and ABC, compared with the resistance levels of the single- or double-amino acid variants (table 1). 2009 The Journal of infectious diseases Result HIV K65R;M184V;Q151M 47;64;53 51;69;58 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Importantly, the addition of either K65R or M184V together with Q151M conferred robust resistance to 3TC and FTC without substantially reducing the level of Q151M-mediated AZT resistance; the HIV-2ROD mutants that contained K65R and Q151M and the mutants that contained Q151M and M184V showed >=70-fold resistance to 3TC and FTC, as well as 29-fold and 56-fold resistance to AZT, respectively (table 1). 2009 The Journal of infectious diseases Result HIV K65R;K65R;M184V;M184V;Q151M;Q151M;Q151M;Q151M 36;224;44;280;64;157;233;270 40;228;49;285;69;162;238;275 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. In comparison with WT HIV-2 RT, Q151M HIV-2 RT exhibited a 15-fold increase in the IC50 for AZT-5'-triphosphate. 2009 The Journal of infectious diseases Result HIV Q151M 32 37 RT;RT 28;44 30;46 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. In contrast to HIV-1NL4-3, HIV-2ROD mutants that harbored M41L, T215Y, or both substitutions showed no detectable resistance to AZT in the single-cycle assay (<2-fold increase in EC50 relative to WT HIV-2ROD) (figure A3 in appendix A, which appears only in the electronic version of the Journal). 2009 The Journal of infectious diseases Result HIV M41L;T215Y 58;64 62;69 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. K65R imparted 38-fold resistance to 3TC and 85-fold resistance to FTC, as well as 4-fold resistance to ddI. 2009 The Journal of infectious diseases Result HIV K65R 0 4 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Over multiple trials, Q151M HIV-2ROD exhibited a mean EC50 for AZT that was 43-fold greater than that for WT HIV-2ROD, whereas the mean EC50 for Q151M HIV-1NL4-3 was only 4-fold greater than that for WT HIV-1NLA-3 (table 1). 2009 The Journal of infectious diseases Result HIV Q151M;Q151M 22;145 27;150 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Q151M had no statistically significant effect on viral sensitivity to PMPA, 3TC, or ABC, but it imparted 5-7-fold resistance to d4T, ddI, and FTC, compared with that of the WT (table 1). 2009 The Journal of infectious diseases Result HIV Q151M 0 5 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Surprisingly, the dose-response profile of Q151M HIV-2ROD was comparable to that of the highly resistant Q151M/A62V/V75I/F77L/F116Y (Q151M+4) HIV-1NL4-3 mutant (figure A2 in appendix A, which appears only in the electronic version of the Journal). 2009 The Journal of infectious diseases Result HIV A62V;F116Y;F77L;Q151M;V75I;Q151M;Q151M 111;126;121;105;116;43;133 115;131;125;110;120;48;137 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Taken together with our cell culture data (table 1), these results demonstrate that the combination of Q151M with either K65R or M184V is sufficient to produce dual resistance to AZT and 3TC in HIV-2. 2009 The Journal of infectious diseases Result HIV K65R;M184V;Q151M 121;129;103 125;134;108 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Taken together, these data demonstrate that Q151M alone is sufficient to produce high-level AZT resistance in HIV-2. 2009 The Journal of infectious diseases Result HIV Q151M 44 49 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. The combination of K65R and Q151M conferred high-level resistance to AZT-5'-triphosphate (an 83-fold increase) and substantial resistance to 3TC-5'-triphosphate (a 7-fold increase) (table 2). 2009 The Journal of infectious diseases Result HIV K65R;Q151M 19;28 23;33 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. The frequency with which K65R, Q151M, and M184V appear together in HIV-2 RT suggests that these replacements define a genetic pathway leading to escape from NRTI-based regimens (figure A1 in appendix A, which appears only in the electronic version of the Journal). 2009 The Journal of infectious diseases Result HIV K65R;M184V;Q151M 25;42;31 29;47;36 NRTI;RT 157;73 161;75 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. The M184V substitution conferred >200-fold resistance to both 3TC and FTC. 2009 The Journal of infectious diseases Result HIV M184V 4 9 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. These findings demonstrate that, in HIV-2ROD, the combination of K65R, Q151M, and M184V confers classwide NRTI resistance, with high-level resistance to AZT, ddI, 3TC, FTC, and ABC. 2009 The Journal of infectious diseases Result HIV K65R;M184V;Q151M 65;82;71 69;87;76 NRTI 106 110 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. This mutant is genetically equivalent to Q151M+4 HIV-1NL4-3 because HIV-2ROD encodes an isoleucine at RT codon 75 that is highly conserved in HIV-2 sequences from treatment-naive patients. 2009 The Journal of infectious diseases Result HIV Q151M 41 46 RT 102 104 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. This result differs substantially from the outcome observed for HIV-1, in which M184V suppresses TAM-mediated AZT resistance by impairing the primer-unblocking activity of RT. 2009 The Journal of infectious diseases Result HIV M184V 80 85 RT 172 174 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. To assess the effects of other replacements that are commonly associated with Q151M in HIV-1, we constructed an A62V/F77L/F116Y/Q151M (Q151M+3) variant of HIV-2ROD. 2009 The Journal of infectious diseases Result HIV A62V;F116Y;F77L;Q151M;Q151M;Q151M 112;122;117;128;78;135 116;127;121;133;83;139 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. To determine whether this outcome was specific to the ROD isolate of HIV-2, we replaced the RT-encoding region of pROD9 (RT codons 14-542) with an equivalent region from the HIV-2UC2-encoding plasmid pUC2 and introduced mutations encoding Q151M into the resultant molecular clone. 2009 The Journal of infectious diseases Result HIV Q151M 239 244 RT;RT 92;121 94;123 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. To further examine the potential for dual AZT-3TC resistance in HIV-2, we quantified the effects of K65R and Q151M on the incorporation of analogue-5'-monophosphate by purified HIV-2 RT. 2009 The Journal of infectious diseases Result HIV K65R;Q151M 100;109 104;114 RT 183 185 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. We also measured the susceptibilities of Q151M-, K65R-, and M184V-containing variants of HIV-2ROD to other NRTIs used in antiretroviral therapy. 2009 The Journal of infectious diseases Result HIV K65R;M184V;Q151M 49;60;41 53;65;46 NRTI 107 112 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. We constructed HIV-1NL4 3 and HIV-2ROD variants encoding 2 pivotal replacements in the TAM series (M41L and T215Y) and compared their sensitivities to AZT. 2009 The Journal of infectious diseases Result HIV M41L;T215Y 99;108 104;113 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. We initially introduced point mutations encoding the Q151M replacement into HIV-2ROD and tested the susceptibility of the resulting variant to AZT. 2009 The Journal of infectious diseases Result HIV Q151M 53 58 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. We therefore examined the individual and combined effects of K65R, Q151M, and M184V on NRTI sensitivity in HIV-2 (table 1). 2009 The Journal of infectious diseases Result HIV K65R;M184V;Q151M 61;78;67 65;83;72 NRTI 87 91 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Among the purchased compounds, 3 shows low-micromolar activity towards both the WT and Y181C-variant HIV-1, while 4 has 7.5-muM activity against the Y181C form, and 5 is a 4.8-muM NNRTI towards the WT virus. 2009 Journal of chemical information and modeling Result HIV Y181C;Y181C 87;149 92;154 NNRTI 180 185 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. For example, 1 and 2 bear some resemblance to PNU142721, which has 1-nM potency towards WT HIV-1, though only 1-muM activity towards a Y181C variant. 2009 Journal of chemical information and modeling Result HIV Y181C 135 140 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Fundamentally, the present virtual screening exercise provided three compounds that are suitable starting points for lead optimization of NNRTIs that are expected to be active against both WT HIV-1 and Y181C RT variants. 2009 Journal of chemical information and modeling Result HIV Y181C 202 207 NNRTI;RT 138;208 144;210 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. In view of the small number of purchased compounds and the prior difficulties in obtaining activity against the Y181C variant, the present virtual screening approach was very successful. 2009 Journal of chemical information and modeling Result HIV Y181C 112 117 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. The lowest XP score is for 4 with the 1jla structure, which is consistent with its activity towards the Y181C variant (Table 2). 2009 Journal of chemical information and modeling Result HIV Y181C 104 109 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. The similarity is apparent when the compounds are aligned as in Scheme 3, which reflects the conformation of PNU142721 in the 1ikx crystal structure with K103N HIV-RT. 2009 Journal of chemical information and modeling Result HIV K103N 154 159 RT 164 166 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. This reinforces the sense that targeting the 1jla and 2be2 structures is appropriate for seeking NNRTIs that do not gain binding affinity via interaction with Tyr181 and are, therefore, resilient to the Y181C mutation. 2009 Journal of chemical information and modeling Result HIV Y181C 203 208 NNRTI 97 103 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. This structure is 1rt4-like, having Y181 and Y188 both "up", and the ligand's furanopyridine moiety is well-stacked with the phenol of Y181, likely accounting for the loss in activity towards the Y181C mutant. 2009 Journal of chemical information and modeling Result HIV Y181C 196 201 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. A CD4 cell count of less than 100 cells/mul was strongly associated with emergence of K65R or K70E, pan-nucleoside resistance, and the emergence of three or more TAMs (Table 3). 2009 AIDS (London, England) Result HIV K65R;K70E 86;94 90;98 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Among patients with exposure to NVP but not to EFV (n =85), the most common mutations were Y181C (55%) and G190A (26%). 2009 AIDS (London, England) Result HIV G190A;Y181C 107;91 112;96 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Among those with exposure to both NVP and EFV (n =9), K103N (33%) and G190A (33%) mutations were the most common. 2009 AIDS (London, England) Result HIV G190A;K103N 70;54 75;59 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Compared with those with ZDV exposure, the emergence of the K65R, Q151M, and K70E mutations was more common in those exposed only to d4T: K65R (24 vs. 2009 AIDS (London, England) Result HIV K65R;K65R;K70E;Q151M 60;138;77;66 64;142;81;71 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Eighteen patients developed virus with the Q151M mutation, and in 15 patients, the Q151M mutation was associated with either K65R or K70E. 2009 AIDS (London, England) Result HIV K65R;K70E;Q151M;Q151M 125;133;43;83 129;137;48;88 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Fifteen patients (16%) had virus with M184V and NNRTI mutations only. 2009 AIDS (London, England) Result HIV M184V 38 43 NNRTI 48 53 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. In spite of no known exposure to TDF, 23% (22/94) of patients acquired virus with the K70E (n =4) or K65R mutations (n =18). 2009 AIDS (London, England) Result HIV K65R;K70E 101;86 105;90 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. In total, 16 patients had pan-nucleoside-resistant virus, on the basis of the presence of the K65R or K70E mutation in association with the Q151M complex or the presence of a 69 insertion. 2009 AIDS (London, England) Result HIV K65R;K70E;Q151M 94;102;140 98;106;145 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Only two of 30 patients who had ever received ZDV developed either K65R/K70E or pan-nucleoside resistance mutations. 2009 AIDS (London, England) Result HIV K65R;K70E 67;72 71;76 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. The M184Vor M184I mutation was present in virus from 77 patients (81%), although never as the only mutation. 2009 AIDS (London, England) Result HIV M184I 12 17 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. The most common mutation pattern was M184V and NNRTI mutations with one or more TAMs, which occurred in 56% of patients. 2009 AIDS (London, England) Result HIV M184V 37 42 NNRTI 47 52 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. The most frequent NNRTI mutations were Y181C (55%), G190A (30%), K103N (28%), K101E (15%), Y188L (8%), V106M (7%), Y181I (6%), K103N/S (2%), P225H (1%), G190S (1%), and G190E (1%). 2009 AIDS (London, England) Result HIV G190A;G190E;G190S;K101E;K103N;K103N;K103S;P225H;V106M;Y181C;Y181I;Y188L 52;169;153;78;65;127;127;141;103;39;115;91 57;174;158;83;70;134;134;146;108;44;120;96 NNRTI 18 23 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. The most frequent TAMs were T215 F/Y (73%), D67N (53%), K70R (36%), M41L (36%), K219 Q/E (23%), and L210W (23%). 2009 AIDS (London, England) Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 44;80;80;56;100;68;28;28 48;88;88;60;105;72;36;36 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Univariate and multivariate analyses were performed to look for associations with the emergence of pan-nucleoside resistance, at least three TAMS, or either K65R or K70E. 2009 AIDS (London, England) Result HIV K65R;K70E 157;165 161;169 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Y181C was significantly more common among NVP-only-exposed patients (55 vs. 2009 AIDS (London, England) Result HIV Y181C 0 5 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. ZDV use was strongly protective for the emergence of K65R or K70E. 2009 AIDS (London, England) Result HIV K65R;K70E 53;61 57;65 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Among these isolates, 6 contained the known RTI-associated resistant mutations, D67N (n=2), K238S (n=2) (http://www.hiv.lanl.gov/content/index), V108I/K238S (n=1) and V106A/V108I/K238S (n=1), and thus were excluded from further analysis. 2009 Antiviral research Result HIV K238S;V106A;V108I;D67N;K238S;K238S;V108I 179;167;173;80;92;151;145 184;172;178;84;97;156;150 RT 44 47 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Further, the combination of A371V and G335D commonly observed in non-B isolates also showed no resistance to AZT, 3TC or ABC (0.7-, 1.0- and 1.1-fold increase in susceptibility as compared to wild-type HIV, respectively). 2009 Antiviral research Result HIV A371V;G335D 28;38 33;43 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Furthermore, the prevalence of V365I in treated and untreated patients in the Stanford HIV Drug Resistance Database is comparable (3.7 and 3.6 %, respectively). 2009 Antiviral research Result HIV V365I 31 36 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. However, HIV-1 protease mutations D30N and M36I that are responsible for resistance to NFV and HIV-1 RT D67N mutation that is responsible for AZT resistance eventually emerged. 2009 Antiviral research Result HIV D30N;D67N;M36I 34;104;43 38;108;47 PR;RT 15;101 23;103 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. However, other studies have shown that combined with EEMs, A371V can confer strong resistance to AZT and has also been recently reported to be associated with weak cross-resistance to 3TC, TNF/PMPA and ABC. 2009 Antiviral research Result HIV A371V 59 64 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. However, V365I may not be clinically relevant, since generally at least 3-fold resistance is required for assigning 3TC resistance in vivo. 2009 Antiviral research Result HIV V365I 9 14 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. In our cohort, ABC inhibits efficiently the clinical isolates that contain the A371V substitution in the absence of EEMs (n=13) either in a subtype B, or non-B background (median fold increase was 0.9-fold, data not shown). 2009 Antiviral research Result HIV A371V 79 84 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. In our cohort, in the absence of EEM mutations, A371V had no significant effect on drug resistance (Table 1). 2009 Antiviral research Result HIV A371V 48 53 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. In the treatment-naive patients of our cohort that were infected with subtype B (n=101), the frequencies of all mutations associated with AZT-resistance were comparable to those (treatment-naive) deposited in the Stanford HIV Drug Resistance Database, except for that of A360T. 2009 Antiviral research Result HIV A360T 271 276 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Isolates with the V365I substitution (n=4 in subtype B) showed slightly reduced susceptibility to 3TC (2.3-fold). 2009 Antiviral research Result HIV V365I 18 23 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Marginal viral suppression was observed in one patient who was infected by HIV-1 carrying A376S and who received combination therapy containing AZT. 2009 Antiviral research Result HIV A376S 90 95 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Moreover, the G335D/A371V combination was observed in 9 (56.3%) of the non-B isolates. 2009 Antiviral research Result HIV A371V;G335D 20;14 25;19 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. None of the clinical isolates of our cohort had the G333D, G335C, N348I, A360I/V, and Q509L mutations. 2009 Antiviral research Result HIV A360I;A360V;G333D;G335C;N348I;Q509L 73;73;52;59;66;86 80;80;57;64;71;91 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Notably, clinical isolates from treatment-naive patients from our cohort with HIV carrying the E312N, G335E/N or A376V substitutions displayed rather enhanced susceptibility (over 5-fold) to AZT and NVP, AZT, 3TC and NVP, and AZT and NVP, respectively (Table 1). 2009 Antiviral research Result HIV A376V;E312N;G335E;G335N 113;95;102;102 118;100;109;109 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Other polymorphisms, including E312A/D/N/T, G335E/N/S, A360S/T, A371T, A376T/V and Q509H, were widely observed in all subtypes in our cohort as well as in the Stanford HIV Drug Resistance Database. 2009 Antiviral research Result HIV A360S;A360T;A371T;A376T;A376V;E312A;E312D;E312N;E312T;G335E;G335N;G335S;Q509H 55;55;64;71;71;31;31;31;31;44;44;44;83 62;62;69;78;78;42;42;42;42;53;53;53;88 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Q509L, which has been reported to enhance cross resistance to NRTIs in the presence of EEMs, conferred little resistance to at least AZT, 3TC and TNF/PMPA in this study. 2009 Antiviral research Result HIV Q509L 0 5 NRTI 62 67 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. The G335D and A371V substitutions were more prevalent in the non-B, rather than in the B isolates of our cohort. 2009 Antiviral research Result HIV A371V;G335D 14;4 19;9 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. The results shown in Table 2 confirm that in the absence of RTI resistance mutations, most substitutions in the connection subdomain and RNase H domain (with the exception of N348I, A376S and Q509L) show no significant resistance to AZT, 3TC, TNF/PMPA, NVP or efavirenz (EFV) (less than 3-fold), suggesting that these mutations act as secondary mutations and may enhance resistance that is caused by primary mutations and/or may somehow improve replication kinetics impaired by the primary mutations. 2009 Antiviral research Result HIV A376S;N348I;Q509L 182;175;192 187;180;197 RT 60 63 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. The treatment-naive patients were classified in four groups; (A) patients who were infected by HIV-1 that carried one or two of the CD substitutions E312Q, G333E, G335D, V365I, A371V or A376S and who subsequently received combination therapy that contained AZT (n=8); (B) patients who were infected by HIV-1 that carried the above CD substitutions and who subsequently received combination therapy that did not contain AZT (n=13); (C) patients who were infected by HIV-1 that did not carry any of the above CD substitutions and who subsequently received combination therapy containing AZT (n=16); and (D) patients who were infected by HIV-1 that did not carry the above CD substitutions and who subsequently received combination therapy that did not contain AZT (n=24). 2009 Antiviral research Result HIV A371V;A376S;E312Q;G333E;G335D;V365I 177;186;149;156;163;170 182;191;154;161;168;175 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Unlike N348I that confers dual resistance to NRTIs and NNRTIs, A376S and Q509L provided only NVP resistance. 2009 Antiviral research Result HIV A376S;N348I;Q509L 63;7;73 68;12;78 NNRTI;NRTI 55;45 61;50 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. In fact, mutating human residue 30 (V30G) moderately reduced its Vpu sensitivity (from 78 to 15 fold) whereas mutating residue 45 (T45I) had a similar impact as mutating all 4 residues (5 fold versus 4 fold rescue on Vpu expression). 2009 PLoS pathogens Result HIV T45I;V30G 131;36 135;40 Vpu;Vpu 65;217 68;220 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. We obtained similar results when the experiment was carried out using the human single point mutant of tetherin T45I demonstrating that this single mutation can render tetherin insensitive to Vpu (Figure 5). 2009 PLoS pathogens Result HIV T45I 112 116 Vpu 192 195 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. We therefore made a human quadruple tetherin mutant I26V, V30G, I36L, T45I and tested its antiviral activity and sensitivity to HIV-1 Vpu. 2009 PLoS pathogens Result HIV I26V;I36L;T45I;V30G 52;64;70;58 56;68;74;62 Vpu 134 137 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. All 5 women with K103N resistance mutations were in the ZDV/sdNVP arm, whereas there were no women with detectable K103N viral variants in the HAART arm. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;K103N 17;115 22;120 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Eight of the 9 women (89%) in the ZDV/sdNVP arm with low levels of Y181C at 3 months posttreatment had detectable levels of Y181C at 12 months posttreatment. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C;Y181C 67;124 72;129 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. For each replicate, we set the proportion of resistance to zero if it was below the lower limit of the assay as defined by replicate testing of wild-type controls: 0.2% and 2% for the K103N and Y181C assays, respectively. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C 184;194 189;199 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. For example, the results for duplicate Y181C assays on virus from patient 569 were below detection (set to zero) for duplicate 1 and 2.2% for duplicate 2. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 39 44 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Frequency of K103N and Y181C Resistance Mutations Detected by Allele-Specific PCR. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C 13;23 18;28 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. In 1 woman (ID# 654), levels were variable over time, but K103N was consistently detected in both #654 and in #629 at 3, 6, and 12 months post-ZDV/sdNVP. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 58 63 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. In most cases, the levels of Y181C were quite stable at all 3 time points, varying at most by ~3-fold over time but showing no evidence of consistent decline. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 29 34 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. In the 5 women with detectable K103N mutations at 3 months posttreatment, K103N levels fell below detection in 3 of the women, whereas the other 2 women (40%) still had detectable K103N mutations at 12 months posttreatment (Table 4). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;K103N;K103N 31;74;180 36;79;185 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. In women treated with HAART, 1 of the 2 women with previously detectable Y181C mutations still had detectable levels of Y181C variants when follow-up ended, 6 months after treatment cessation (Table 5). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C;Y181C 73;120 78;125 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. K103N mutations were detected by allele-specific PCR in 5 of the 27 women (19%) included here (Table 2). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 0 5 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Nine of 16 women (56%) in the ZDV/sdNVP arm and 2 of 11 women (18%) in the HAART arm had viral variants with detectable levels of Y181C. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 130 135 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Only 2 of the women had detectable levels of both K103N and Y181C mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C 50;60 55;65 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. The frequency of detectable K103N and/or Y181C viral variants 3 months after treatment cessation in the ZDV/sdNVP arm was 75%, whereas only 18% in the HAART arm (Table 2). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C 28;41 33;46 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. The levels of K103N detected by allele-specific PCR ranged from 0.8% to 3% of total virus, and levels of Y181C ranged from 1.1% to 14.2% (Table 1). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C 14;105 19;110 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Therefore, in 2 cases in which a sample had replicate results both above and below the lower limit for a single allele-specific assay, the average reported is less than the 2% lower limit for Y181C (Table 1). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 192 197 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Therefore, we report the estimated proportion of Y181C virus in that patient to be 1.1%: the average of the duplicate tests. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 49 54 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. We used allele-specific PCR to examine low levels of K103N and Y181C viral variants in the samples from 3 months after treatment cessation. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C 53;63 58;68 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. We used allele-specific PCR to examine whether the low levels of K103N and Y181C viral variants detected at 3 months after treatment cessation were also present at 6 or 12 months posttreatment. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C 65;75 70;80 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Y181C mutations were detected by allele-specific PCR in 11 of the 27 women (41%) (Table 2). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 0 5 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. 98.78% of all analyzed sequences contained R (arginine) in position 90 indicating that this amino acid is highly conserved. 2009 PloS one Result HIV R90R 40 73 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. A specific signal was obtained in DC lysates transfected with the full length Vpr ( Figure 5 , panel B) however, the expression levels of the truncated Vpr or R90K mutant are decreased dramatically by comparison. 2009 PloS one Result HIV R90K 159 163 Vpr;Vpr 78;152 81;155 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Although all Vpr RNAs are translated in the DC, both the truncated form and the R90K mutant are rapidly degraded and the lack of their expression persistence may explain their non-interference with IL-12 secretion. 2009 PloS one Result HIV R90K 80 84 Vpr 13 16 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. At least two reports link the R77Q substitution in Vpr with long-term non-progression (LTNP) of HIV-infected patients. 2009 PloS one Result HIV R77Q 30 34 Vpr 51 54 HIV infections 96 108 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. C-terminal deletion or R90K mutation leads to Vpr protein degradation via ubiquitin-dependent pathway. 2009 PloS one Result HIV R90K 23 27 Vpr 46 49 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Expression of AXXLL and R77Q Vpr RNAs was confirmed in vitro (Data not shown). 2009 PloS one Result HIV R77Q 24 28 Vpr 29 32 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Given than none of the mutations tested above demonstrated any impact on IL-12 secretion, we next created a new series of mutations within the C-terminal region: R90K as well as deletion of the last three amino acid residues, eliminating both S94 and S96 (DeltaSRS). 2009 PloS one Result HIV R90K 162 166 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. If the R77 residue is responsible for the IL-12 suppression it is expected that Q77 would relieve the IL-12 suppression and the reverse mutation Q77R will have the opposite effect. 2009 PloS one Result HIV Q77R 145 149 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. In addition continuous suppression of IL-12 in the DC electroporated with the AXXLL and R77Q Vpr RNA indirectly suggests lack of those mutations on the expression of Vpr in DC. 2009 PloS one Result HIV R77Q 88 92 Vpr;Vpr 93;166 96;169 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. In addition, we created the reverse substitution, Q77R in the p98CN009.8 background. 2009 PloS one Result HIV Q77R 50 54 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. In order to confirm that proteins were expressed from wild-type, truncated and R90K mutant RNAs we conducted studies using Western blot analysis. 2009 PloS one Result HIV R90K 79 83 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. In the presence of lactacystin, there was an accumulation of the Vpr-specific signals using lysates of DC electroporated with truncated Vpr or the R90K mutant. 2009 PloS one Result HIV R90K 147 151 Vpr;Vpr 65;136 68;139 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. In the presence of the inhibitor of ubiquitin-mediated degradation, the levels of the truncated form of Vpr and the R90K mutant are elevated. 2009 PloS one Result HIV R90K 116 120 Vpr 104 107 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. More interestingly, cultures of DC electroporated with R90K Vpr had levels of IL-12 comparable to those observed using the C-terminal Vpr truncation or in the complete absence of Vpr RNA (GFP control). 2009 PloS one Result HIV R90K 55 59 Vpr;Vpr;Vpr 60;134;179 63;137;182 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Of all amino acid substitutions tested in position 90, only the R90K relieves the suppression of IL-12. 2009 PloS one Result HIV R90K 64 68 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. R90 and R90K were also used in the same experiment as controls ( Figure 6 ). 2009 PloS one Result HIV R90K 8 12 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Since amino acid 77 is not involved, it was not surprising that the reverse mutant Q77R did not differ from the wild-type p98CN009.8 and suppressed IL-12 secretion as well. 2009 PloS one Result HIV Q77R 83 87 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. The HIV clone, p98CN009.8, contains Vpr with a Glutamine (Q) in position 77 and we used it to prepare Vpr RNA encoding Q77. 2009 PloS one Result HIV Q77Q 44 78 Vpr;Vpr 36;102 39;105 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. The R90 residue is highly conserved in Vpr and R90K is the only substitution tested which relieves the IL-12 suppression. 2009 PloS one Result HIV R90K 47 51 Vpr 39 42 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. The R90K and DeltaSRS mutants were created in the background of the p98CN009.8 clone. 2009 PloS one Result HIV R90K 4 8 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. These data clearly show that a single conservative amino acid substitution, R90K, in full length Vpr prevents the IL- 12 blockade in DC. 2009 PloS one Result HIV R90K 76 80 Vpr 97 100 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. These data indicated that the presence of the C-terminal truncation or R90K mutation do not impact on the ability of the ribosomal machinery to translate Vpr RNAs. 2009 PloS one Result HIV R90K 71 75 Vpr 154 157 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. In 10 patients a combination of V184M and at least one mutation conferring to NNRTI-class resistance was observed. 2009 AIDS research and therapy Result HIV V184M 32 37 NNRTI 78 83 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. In one patient the multi-drug resistant Q151M mutation was seen and two patients carried virus with a K65R mutation, all three combined with V184M (Table S2; Additional File 2). 2009 AIDS research and therapy Result HIV K65R;Q151M;V184M 102;40;141 106;45;146 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. Overall, the V184M was most commonly observed (n = 12), followed by K103N (n = 9). 2009 AIDS research and therapy Result HIV K103N;V184M 68;13 73;18 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. A total of 10 individuals (9.0%), all taking d4T, had developed the K65R mutation, limiting future use of ddI, tenofovir and abacavir, without having had exposure to any of these medications (Table 4). 2009 Antiviral therapy Result HIV K65R 68 72 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. According to the genotypic resistance interpretation algorithm four (4.0%) more people were likely to have intermediate resistance to 3TC and FTC due to the presence of K65R (Table 4). 2009 Antiviral therapy Result HIV K65R 169 173 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Despite this cohort having no prior NNRTI exposure, there were two individuals with single NNRTI mutations (1.7%), one Y181C and one G190A, In contrast to the RT, in the protease inhibitor region there were a number of mutations which occurred frequently, though these were not expected to cause drug resistance. 2009 Antiviral therapy Result HIV G190A;Y181C 133;119 138;124 PR;NNRTI;NNRTI;RT 170;36;91;159 178;41;96;161 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. In this group, those with the K65R did not have a significantly higher mean viral load than those without. 2009 Antiviral therapy Result HIV K65R 30 34 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. In total, 97 individuals (88%) had one or more therapy-limiting NNRTI mutations (table 3), including K103N (55%), V106M (31%) and Y181C (10%) and probable drug susceptibility according to the genotypic interpretation algorithm was poor (Table 4). 2009 Antiviral therapy Result HIV K103N;V106M;Y181C 101;114;130 106;119;135 NNRTI 64 69 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. One individual (0.8%) had a K65R mutation, denoting probable reduced sensitivity to tenofovir and abacavir, and 3 had the V118I mutation (2.5%). 2009 Antiviral therapy Result HIV K65R;V118I 28;122 32;127 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. presenting with the M184V mutation (n=6, 5.4%), or NNRTIs alone (n=20, 18%). 2009 Antiviral therapy Result HIV M184V 20 25 NNRTI 51 57 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Six (5.5%) individuals had both the K65R and the M184V mutations. 2009 Antiviral therapy Result HIV K65R;M184V 36;49 40;54 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The M184V, conferring resistance to 3TC and emtricitabine (FTC), was the most common single mutation (n=86, 78%) and emerged rapidly in failure (Figure 1a). 2009 Antiviral therapy Result HIV M184V 4 9 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The most frequent protease mutations remained M36I (86%), L63P (60%), H69K (94%) and L89I/M (82%), similar to the consensus sequence noted for clade C (differing amino acids compared to clade B subtypes at positions M361, R41K, H69K AND L89M). 2009 Antiviral therapy Result HIV H69K;H69K;L63P;L89I;L89M;L89M;M36I;R41K 70;228;58;85;237;85;46;222 74;232;62;91;241;91;50;226 PR 18 26 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The most frequent protease mutations were L89I/M (89%), H69K (88%), L63P (52%) and M36I (87%). 2009 Antiviral therapy Result HIV H69K;L63P;L89I;L89M;M36I 56;68;42;42;83 60;72;48;48;87 PR 18 26 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The ratio of V106M/K103N in patients failing EFV therapy was 0.5. 2009 Antiviral therapy Result HIV K103N;V106M 19;13 24;18 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The Y181C emerged more frequently in those failing nevirapine (8 of 25, 32%) than efavirenz (3 of 85, 3.5%, p=0.0004). 2009 Antiviral therapy Result HIV Y181C 4 9 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. There was no significant difference in the emergence of K103N whether nevirapine (9 of 25, 36%) or efavirenz (51 of 85, 60%) was taken (p=0.229).There was no significant difference in the emergence of V106M by drug. 2009 Antiviral therapy Result HIV K103N;V106M 56;201 61;206 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. all products of the Gag-Pol polyprotein, IN p32, PR p11 and CA p24, were detected in the mutants Y271A and I274A at a level similar to that of the wild type pseudoviral particles. 2009 PloS one Result HIV I274A;Y271A 107;97 112;102 GagPol;p24;IN;Capsid;PR 20;63;41;60;49 27;66;43;62;51 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. However, the formation of homodimer in mutant Y271A was markedly reduced and a higher order oligomer appeared, which might be tetramer according to its molecular weight, while mutant I274A existed as at least two higher order oligomers, which were likely tetramer and octamer based on their molecular weights. 2009 PloS one Result HIV I274A;Y271A 183;46 188;51 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. In the presence of indinavir, however, both RT p66 and p55 were markedly reduced in the wild type virus but became detectable in mutant Y271A viral particles, while RT p66 was also detectable in mutant I274A virus. 2009 PloS one Result HIV I274A;Y271A 202;136 207;141 RT;RT 44;165 46;167 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Mutants Y271A and I274A were undetectable in U373-MAGI-CXCR4CEM cells. 2009 PloS one Result HIV I274A;Y271A 18;8 23;13 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Mutations Y271A and I274A did not affect Pr160gag-pol expression and transportation. 2009 PloS one Result HIV I274A;Y271A 20;10 25;15 Pol;PR 50;41 53;43 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. RT activity and RT proteins were undetectable in pseudoviral particles of mutants Y271A and I274A. 2009 PloS one Result HIV I274A;Y271A 92;82 97;87 RT;RT 0;16 2;18 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. The Gag-Pol polyprotein was incorporated into mutant virions of Y271A and I274A, but the RT was degraded by viral protease. 2009 PloS one Result HIV I274A;Y271A 74;64 79;69 PR;GagPol;RT 114;4;89 122;11;91 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. The RT activity recovered from mutants Y271A and I274A were almost unnoticeable, as compared with that of wild type. 2009 PloS one Result HIV I274A;Y271A 49;39 54;44 RT 4 6 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. These results suggested that the Y271A and I274A RTs were degraded after incorporation of Gag-Pol polyprotein into the virions, which might be attributed to the activity of viral protease. 2009 PloS one Result HIV I274A;Y271A 43;33 48;38 PR;GagPol;RT 179;90;49 187;97;52 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. This result was further confirmed using wild type, Y271A and I274A live viruses (data not shown). 2009 PloS one Result HIV I274A;Y271A 61;51 66;56 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. To confirm the above results, replication of wild type, Y271A and I274A live viruses was further monitored in U373-MAGI-CXCR4CEM and MT2 cells. 2009 PloS one Result HIV I274A;Y271A 66;56 71;61 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. To investigate whether the precursor Gag-Pol polyprotein was indeed incorporated into pseudoviral particles of mutants Y271A and I274A, products of the Gag-Pol polyprotein, integrase (IN), protease (PR) and p24, in wild type and mutant pseudoviral particles were examined by Western blotting. 2009 PloS one Result HIV I274A;Y271A 129;119 134;124 IN;PR;GagPol;GagPol;p24;IN;PR 173;189;37;152;207;184;199 182;197;44;159;210;186;201 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. To study if the RTs in the viral particles of Y271A and I274A mutants were degraded by proteolysis that made them undetectable, pseudoviruses of wild type and mutants were generated in the presence or absence of indinavir, a highly specific inhibitor of HIV-1 protease. 2009 PloS one Result HIV I274A;Y271A 56;46 61;51 PR;RT 260;16 268;19 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. When Jurkat cells were infected with the wild type and mutant pseudoviruses (250 ng p24 virus/5x105 cells), viral replication was almost completely inhibited in the mutants Y271A and I274A, while replication of other mutants did not show significant difference as compared to that of the wild type. 2009 PloS one Result HIV I274A;Y271A 183;173 188;178 p24 84 87 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Y271A and I274A mutations abrogated viral replication. 2009 PloS one Result HIV I274A;Y271A 10;0 15;5 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Y271A and I274A substitutions affected dimer-formation of RT. 2009 PloS one Result HIV I274A;Y271A 10;0 15;5 RT 58 60 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. The most frequent mutations were M184I/V (n = 14; 64%), conferring resistance to lamivudine, and K103N (n = 6; 27%), Y181C (n = 6; 27%) and G190A (n = 6; 27%), conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). 2009 BMC infectious diseases Result HIV G190A;K103N;M184I;M184V;Y181C 140;97;33;33;117 145;102;40;40;122 NNRTI;NNRTI 185;234 221;240 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. 24/37 (64.9%) patients with K65R were on TDF-containing first line ART. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 28 32 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. A comparison of drug resistance mutations between patients with (n =37) and without (n=301) the K65R mutation was also performed. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 96 100 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. A variety of NRTI mutations were observed in association with the K65R mutation [Table 2] with some notable differences between patients with and without TDF in their first line ART regimen. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 66 70 NRTI 13 17 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Among 21 patients primarily on TDF containing ART, the following mutations were observed: M184V, M184I, S68G, A62V and Y115F and K219E. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV A62V;K219E;M184I;M184V;S68G;Y115F 110;129;97;90;104;119 114;134;102;95;108;124 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Among patients with the K65R mutation, the median duration of ART therapy prior to the first genotypic test was 13.4 months (range 6.4-45.2 months), the median time between detection of failure and first genotypic test was 5.72 months (range 0-26.2) and the median viral load and CD4+ cell count at the time of genotypic testing was 70,469.5 copies/ml (range 2318-1,037,171) and 84 cells/mm3 (range 4-469) respectively. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 24 28 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Among the 13 patients on non-TDF ART, the following NRTI mutations were observed in association with the K65R mutation: Q151M, F77L, F116Y, V75I, M184V, K219R, T69del and S68G. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV F116Y;F77L;K219R;K65R;M184V;Q151M;S68G;T69del;V75I 133;127;153;105;146;120;171;160;140 138;131;158;109;151;125;175;166;144 NRTI 52 56 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Mutations that occurred significantly more commonly in patients on non-TDF ART than those on TDF containing ART included Q151M complex mutations (p <0.05), and the combination of K219R and T69del mutations, which always appeared together [6/13 (46.2%) vs. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K219R;Q151M;T69del 179;121;189 184;126;195 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. TAMs were very infrequent among both groups of patients with the K65R mutation and there were no significant differences between them (p>0.05). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 65 69 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The following mutations were observed in significantly more patients with K65R: S68G, A62V, Y115F, Q151M complex, T69del and K219R [all p<0.01]. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV A62V;K219R;K65R;Q151M;S68G;T69del;Y115F 86;125;74;99;80;114;92 90;130;78;104;84;120;97 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The K65R mutation was detected in 37/338 (10.9%) patients. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 4 8 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The most common NNRTI mutations included: Y181C (168, 49.7%), K103N (123, 36.4%), G190A (89, 26.3%), A98G (66, 19.5%), K101E (59, 17.5%), V108I (52, 15.4%), and V90I (41, 12.1%). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV A98G;G190A;K101E;K103N;V108I;V90I;Y181C 101;82;119;62;138;161;42 105;87;124;67;143;165;47 NNRTI 16 21 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The most common NRTI mutations observed were M184V (301, 89.1%), K70R (91, 26.9%), D67N (75, 22.2%), T215Y (61, 18.0%), T215F (51, 15.1%), M41L (46, 13.6%), K219Q (45, 13.3%), S68G (43, 12.7%), and K65R (37, 10.9%). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV D67N;K219Q;K65R;K70R;M184V;M41L;S68G;T215F;T215Y 83;157;198;65;45;139;176;120;101 87;162;202;69;50;143;180;125;106 NRTI 16 20 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The most prevalent HIV-1 subtype among patients with K65R was CRF02_AG (21/37; 56.8%). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 53 57 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The remaining 13(35.1%) patients with K65R had only received a combination of stavudine or zidovudine, lamivudine, and nevirapine and had no documented prior exposure to tenofovir. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 38 42 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The S68G mutation was also seen more frequently in patients on non-TDF ART but this finding was not significant [9/13 (69.2%) vs. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV S68G 4 8 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. There was one reported death in our K65R cohort with no further information. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 36 40 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. For PIs, L90M appeared most often (n=6), followed by I84V (n=3). 2009 Antiviral therapy Result HIV I84V;L90M 53;9 57;13 PI 4 7 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. K103N was detected in 19 subjects (7.5%), making it the most commonly detected mutation. 2009 Antiviral therapy Result HIV K103N 0 5 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. K65R was detected only once. 2009 Antiviral therapy Result HIV K65R 0 4 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. Less frequently seen NNRTI SDRMs included Y181C (n=3), G190A/S (n=2), and Y188L (n=1). 2009 Antiviral therapy Result HIV G190A;G190S;Y181C;Y188L 55;55;42;74 62;62;47;79 NNRTI 21 26 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. M184V was seen only in samples from two recently infected individuals. 2009 Antiviral therapy Result HIV M184V 0 5 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. M46I, F53L, and G73S were each seen in only two samples each. 2009 Antiviral therapy Result HIV F53L;G73S;M46I 6;16;0 10;20;4 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. Seven recently infected subjects harbored T215C or T215D revertant mutations, which represent the first back-mutation away from T215Y. 2009 Antiviral therapy Result HIV T215C;T215D;T215Y 42;51;128 47;56;133 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. The most common TAM was M41L, occurring in 5 cases; D67N and K219Q were each present in 3 samples. 2009 Antiviral therapy Result HIV D67N;K219Q;M41L 52;61;24 56;66;28 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. 40 of the 42 (3.1% of the total) patients with the RT mutation K103N had no other detectable drug-resistance mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 63 68 RT 51 53 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Among the 12 samples with NNRTI-resistance mutations, seven had a total of 11 major etravirine-resistance mutations including L100I (n=2), K101E (n=2), Y181C (n=2), G190A/S (n=5). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;G190S;K101E;L100I;Y181C 165;165;139;126;152 172;172;144;131;157 NNRTI 26 31 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. By SGRT, 437 (41%) of these patients had a plasma sample containing K103N obtained while receiving a failing NNRTI-containing regimen including 160 patients (15%) whose virus samples exhibited no other major NNRTI-resistance mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 68 73 NNRTI;NNRTI 109;208 114;213 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Five samples had one or more NRTI or NNRTI-resistance mutation including 30062 which had four NRTI-resistance mutations: M184V+L210W+T215Y+219Q and 8048 had one NRTI-resistance mutation K65R and one NNRTI-resistance mutation P225H. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R;L210W;M184V;P225H;T215Y 186;127;121;225;133 190;132;126;230;138 NNRTI;NNRTI;NRTI;NRTI;NRTI 37;199;29;94;161 42;204;33;98;165 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Four samples had a total of five accessory etravirine-resistance mutations (V90I, V106I, V179D) including two of the seven with major mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV V106I;V179D;V90I 82;89;76 87;94;80 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Furthermore, the overall number of nonpolymorphic etravirine-resistance mutations were significantly higher among those with acquired vs transmitted K103N (13 vs 0 mutations; p=0.02; Wilcoxon Rank Sum Test). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 149 154 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. However, there was no significant difference in the number of polymorphic etravirine-resistance mutations (V90I, V106I, and V179D) between those with acquired and transmitted K103N (4/20 vs 2/13; p=NS). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;V106I;V179D;V90I 175;113;124;107 180;118;129;111 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. In addition to K103N, the RT sequence from one patient had the accessory NNRTI-resistance mutation P225H. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;P225H 15;99 20;104 NNRTI;RT 73;26 78;28 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. In conclusion, significantly more patients with acquired K103N than with transmitted K103N were infected with viruses containing nonpolymorphic etravirine-resistance mutations (7/20 vs. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;K103N 57;85 62;90 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. NNRTI-Experiencing Patients with Virus Samples Containing Acquired K103N Mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 67 72 NNRTI 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. No NNRTI-resistance mutations as high as 0.5% with the exception of K103S (a likely K103N revertant) which was detected in 0.6% and 0.9% of reads from samples 8048 and 28010, respectively. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;K103S 84;68 89;73 NNRTI 3 8 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. One patient (8048) was treated with LPV in combination with d4T + abacavir for seven years but was poorly adherent and eventually developed the LPV resistance mutations (I54V and V82A). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV I54V;V82A 170;179 175;183 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Previously Untreated Patients with Virus Samples Containing Transmitted K103N. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 72 77 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Six of the patients with transmitted K103N (16387, 22138, 25590, 27791, 27834, 30074) were treated with a regimen containing ritonavir-boosted atazanavir (n=4) or lopinavir (n=2) in combination with TDF + 3TC, FTC or ddI. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 37 42 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Ten of the 12 samples had a total of 14 non-etravirine resistance mutations including V108I (n=6), P225H (n=3), K101N (n=1), Y188C (n=1). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV K101N;P225H;V108I;Y188C 112;99;86;125 117;104;91;130 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The accessory NNRTI-resistance mutations P225H (n=3), V108I (n=1), A98G (n=1), and H221Y (n=1) were detected in six of the samples. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV A98G;H221Y;P225H;V108I 67;83;41;54 71;88;46;59 NNRTI 14 19 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The polymorphic etravirine-associated mutations V90I and V106I were each detected in one sample. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV V106I;V90I 57;48 62;52 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The sample from PID 30062 - which contained four NRTI-resistance mutations - also had the following minority protease inhibitor (PI) resistance mutations: M46I (0.8%), I84V (0.9%), and L90M (0.9%) (data not shown). 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV I84V;L90M;M46I 168;185;155 172;189;159 PR;NRTI;PI 109;49;129 117;53;131 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Twelve samples had established NRTI-resistance mutations including M184V/I in 9 samples and T215F/Y in 6 samples. 2009 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V;T215F;T215Y 67;67;92;92 74;74;99;99 NRTI 31 35 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. A88V conferred sensitivity to restriction. 2009 Nature structural & molecular biology Result HIV A88V 0 4 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Also, mutation between arginine and histidine (in R69H (DH)) preserves the positive charge, whereas switching between aspartic acid and asparagine (in D66N (NR)) results in loss of a negative charge and is therefore considerably more destabilizing. 2009 Nature structural & molecular biology Result HIV D66N;R69H 151;50 155;54 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. First, we compared binding of RhTC CypA (NH) and the individual CypA mutants D66N (NR) and R69H (DH) to HIV-1 and HIV-2 capsids (CAN domain) by ITC. 2009 Nature structural & molecular biology Result HIV D66N;R69H 77;91 81;95 Capsid 120 127 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Mutation D66N disrupts a bifurcated hydrogen bond with the main chain nitrogen atoms of residues 73 and 74 that constrains the conformation of loop64-74. 2009 Nature structural & molecular biology Result HIV D66N 9 13 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Next, we attempted to address why HIV-2 binds CypA weakly and how D66N and R69H increase affinity. 2009 Nature structural & molecular biology Result HIV D66N;R69H 66;75 70;79 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Next, we tested the single mutation R69H (DH) and found that it broadened CypA binding specificity by maintaining micromolar binding to HIV-1 CAN and also conferring micromolar binding to HIV-2 CAN. 2009 Nature structural & molecular biology Result HIV R69H 36 40 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. The CypA domain of RhTC has two coding mutations (D66N and R69H) with respect to the parental CypA gene. 2009 Nature structural & molecular biology Result HIV D66N;R69H 50;59 55;63 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. The HIV-2 and RhTC structures suggest that HIV-1 and HIV-2 have alternative loop conformations caused by a conserved deletion in position CA 88 and that these different loop conformations are differentiated by a new active site conformation in RhTC caused by the D66N and R69H mutations. 2009 Nature structural & molecular biology Result HIV D66N;R69H 263;272 267;276 Capsid 138 140 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. The second single mutation, D66N (NR), switched the binding specificity of CypA from HIV-1 CAN to HIV-2 CAN. 2009 Nature structural & molecular biology Result HIV D66N 28 32 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. thus, the M88A mutant behaved similarly to an M group HIV-1. 2009 Nature structural & molecular biology Result HIV M88A 10 14 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. To address the effects of RhTC mutations D66N and R69H, we solved the structure of its CypA domain to 1.5-A resolution. 2009 Nature structural & molecular biology Result HIV D66N;R69H 41;50 45;54 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. To show that these changes are not context dependent, we made the reciprocal M88A mutant in O group MVP5180 and showed that this abolished restriction by RhTC (NH) and mutant NR, while maintaining restriction by DH and CypTC (DR). 2009 Nature structural & molecular biology Result HIV M88A 77 81 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. To test whether variation in position CA 88 is sufficient to alter sensitivity to RhTC, we made a single A88V mutation in a HIV-1 M group virus. 2009 Nature structural & molecular biology Result HIV A88V 105 109 Capsid 38 40 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. Additionally, two HIV-1 RT mutants, K103N and Y181C, were used and analyzed by mutating positions 103 and 181 of the wild-type structure through the use of the Sybyl 7.2 program. 2009 Beilstein journal of organic chemistry Result HIV K103N;Y181C 36;46 41;51 RT 24 26 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. Compound 5, without methoxy substituent, was found to be slightly more potent than 6 except for Y181C mutant RT. 2009 Beilstein journal of organic chemistry Result HIV Y181C 96 101 RT 109 111 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. For 6, H-bond interaction between a hydrogen atom of the methoxy group of 6 and an oxygen atom of backbone Lys104 revealed a longer bond length (3.58 A) in the Y181C binding pocket as compared to the WT binding pocket (2.14 A). 2009 Beilstein journal of organic chemistry Result HIV Y181C 160 165 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. For 9, stronger attractive interactions with the backbone oxygen atoms of Val179 and Tyr188 in the Y181C binding pocket were formed as compared with the WT binding pocket. 2009 Beilstein journal of organic chemistry Result HIV Y181C 99 104 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. However, 9 showed better potency against the Y181C mutant RT compared to the other two compounds. 2009 Beilstein journal of organic chemistry Result HIV Y181C 45 50 RT 58 60 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. In the case of the docked conformations of 5, 6 and 9 in the K103N binding pocket, the H-bond interactions with the backbone atom of Asn103 were still detected, but their H-bond interactions with Val106 were lost. 2009 Beilstein journal of organic chemistry Result HIV K103N 61 66 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. In the wild-type and K103N binding sites, the docked orientations of 5, 6 and 9 are similar to that of nevirapine. 2009 Beilstein journal of organic chemistry Result HIV K103N 21 26 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. In the Y181C binding pocket, it was found that the docked conformation of 5 had a different orientation compared to 6 and 9. 2009 Beilstein journal of organic chemistry Result HIV Y181C 7 12 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. In the Y181C binding site, except for 5, the orientations of the others were similar to nevirapine orientation. 2009 Beilstein journal of organic chemistry Result HIV Y181C 7 12 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. Interestingly, 5 and 6 were found to be about four times more potent against WT-RT than 9, and they provided comparable activity against K103N mutant RT. 2009 Beilstein journal of organic chemistry Result HIV K103N 137 142 RT;RT 80;150 82;152 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. The GoldScores of 5, 6 and 9 were higher than those of nevirapine by 17.61-24.56, 9.52-15.00 and 15.33-21.06 in the WT, K103N, and Y181C binding pockets, respectively. 2009 Beilstein journal of organic chemistry Result HIV K103N;Y181C 120;131 125;136 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. The results from the biological testing of all compounds synthesized, compared with nevirapine (1) and 9, against the wild-type RT together with K103N and Y181C mutant RT are shown in Table 1. 2009 Beilstein journal of organic chemistry Result HIV K103N;Y181C 145;155 150;160 RT;RT 128;168 130;170 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. A comparison of the crystal structures of the RT ternary complexes suggests that the stacking of the guanidinium groups of K65R and the conserved Arg72 imposes a constraint on adaptability of both of the amino acid residues. 2009 The Journal of biological chemistry Result HIV K65R 123 127 RT 46 48 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Amino acid residues K65R, Arg72, and Tyr115, which interact with TFV-DP, are clearly defined in the electron density map. 2009 The Journal of biological chemistry Result HIV K65R 20 24 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Biochemical studies showed that the K65R mutation can cause drug resistance to NRTIs and reduce both the nucleotide incorporation and excision by RT. 2009 The Journal of biological chemistry Result HIV K65R 36 40 NRTI;RT 79;146 84;148 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Comparison of the wild type and K65R mutant structures shows similar RT conformation, mode of dsDNA-binding, and crystal packing; the root mean square deviation for all Calpha atoms is ~0.5 A when both structures are overlaid. 2009 The Journal of biological chemistry Result HIV K65R 32 36 RT 69 71 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. In all studies, the K65R mutant shows a modest decrease in the incorporation rate (kpol) for dATP (4.5-fold) without a significant change in the binding affinity (Kd). 2009 The Journal of biological chemistry Result HIV K65R 20 24 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. In the TFV-DP-bound K65R RT structure, Arg72 has a rotameric conformation (rotamer-2) that is analogous to the orientation of Arg72 in the wild-type RT dsDNA TFV-DP structure but distinct from a common R72 rotamer (rotamer-1) in dATP-, dTTP-, and AZTppppA-bound RT dsDNA structures4; the two distinct rotameric conformations of Arg72 differ by ~1.6 A at the position of Nepsilon. 2009 The Journal of biological chemistry Result HIV K65R 20 24 RT;RT;RT 25;149;262 27;151;264 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R RT is resistant to TFV-DP and ddATP because the mutation dramatically decreases the incorporation of these analogs (>20-fold). 2009 The Journal of biological chemistry Result HIV K65R 0 4 RT 5 7 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R showed a comparably slower kpol for incorporation of dATP and dATP-alpha-S by 4.2- and 4.9-fold, respectively. 2009 The Journal of biological chemistry Result HIV K65R 0 4 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Our attempt to co-crystallize dATP with the 27:21-mer dsDNA cross-linked K65R mutant RT produced crystals that had a shape similar to the rodlike crystals of K65R RT dsDNA TFV-DP complex; however, the crystals of the dATP complex did not grow to a size suitable for diffraction studies. 2009 The Journal of biological chemistry Result HIV K65R;K65R 73;158 77;162 RT;RT 85;163 87;165 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Ternary Complex of K65R Mutant RT dsDNA dATP. 2009 The Journal of biological chemistry Result HIV K65R 19 23 RT 31 33 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Ternary Complex of K65R Mutant RT dsDNA TFV-DP. 2009 The Journal of biological chemistry Result HIV K65R 19 23 RT 31 33 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The adenine bases and the triphosphates of TFV-DP and dATP superimpose when the two ternary complex structures of K65R mutant RT are compared. 2009 The Journal of biological chemistry Result HIV K65R 114 118 RT 126 128 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The crystal structure of K65R RT 27:21-mer dsDNA TFV-DP (supplemental. 2009 The Journal of biological chemistry Result HIV K65R 25 29 RT 30 32 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The elemental effect for wild-type and K65R RT was investigated (Table 3). 2009 The Journal of biological chemistry Result HIV K65R 39 43 RT 44 46 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The guanidinium plane of K65R is stacked with the guanidinium plane of Arg72 with an approximate distance of 3.8 A between the two guanidinium planes. 2009 The Journal of biological chemistry Result HIV K65R 25 29 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The major difference between wild-type and the K65R RT structures is at the beta3-beta4 fingers loop. 2009 The Journal of biological chemistry Result HIV K65R 47 51 RT 52 54 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The mutated residue K65R has an orientation similar to Lys65 in the wild-type RT dsDNA TFV-DP and wild-type RT dsDNA dTTP structures where one of the guanidinium Neta nitrogens interacts with the gamma-phosphate oxygen (N . 2009 The Journal of biological chemistry Result HIV K65R 20 24 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The other guanidinium Neta nitrogen of K65R interacts with the oxygen atom linking the beta- and gamma-phosphates of TFV-DP, which mimics the interaction of K65 with TFV-DP in the wild-type RT dsDNA TFV-DP structure. 2009 The Journal of biological chemistry Result HIV K65R 39 43 RT 190 192 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The overall structure of K65R RT dsDNA dATP complex is similar to that of K65R RT dsDNA TFV-DP complex. 2009 The Journal of biological chemistry Result HIV K65R;K65R 25;74 29;78 RT;RT 30;79 32;81 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The presence of only one metal ion at the active site of the current structure was confirmed by determining the crystal structure of K65R RT dsDNA TFV-DP with Mn2+ ions (supplemental. 2009 The Journal of biological chemistry Result HIV K65R 133 137 RT 138 140 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The side chain of K65R also has two rotameric conformations, depending on whether dATP or TFV-DP is bound. 2009 The Journal of biological chemistry Result HIV K65R 18 22 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The ternary complex of K65R RT crystallized in a crystal form similar to that of wild-type RT dsDNA TFV-DP. 2009 The Journal of biological chemistry Result HIV K65R 23 27 RT;RT 28;91 30;93 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. These different rotamers facilitate better stacking of the guanidinium planes of K65R and Arg72 in the two structures. 2009 The Journal of biological chemistry Result HIV K65R 81 85 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Three independent pre-steady state analyses of K65R incorporation of dATP versus the NRTIs TFV-DP and ddATP (the active metabolite of ddI) are summarized in Table 2. 2009 The Journal of biological chemistry Result HIV K65R 47 51 NRTI 85 90 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Thus, the elemental effect observed for wild-type and K65R mutant HIV-1 RT was 1.0 and 1.1, respectively (Table 3), supporting the hypothesis that the K65R mutation slows the rate-limiting conformational step for nucleotide incorporation, probably by conformational restriction by the K65R/Arg72 molecular platform rather than the chemical step of incorporation. 2009 The Journal of biological chemistry Result HIV K65R;K65R;K65R 54;151;285 58;155;289 RT 72 74 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. To obtain a better understanding of how the K65R mutation helps RT discriminate between TFV-DP and dATP, we also determined the crystal structure of the K65R mutant RT dsDNA dATP complex. 2009 The Journal of biological chemistry Result HIV K65R;K65R 44;153 48;157 RT;RT 64;165 66;167 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Among all ARV-treated patients, 76.4% harbored M184V and 31.3% harbored K70R, both of which result from a A G transition. 2005 Journal of the International AIDS Society Result HIV K70R;M184V 72;47 76;52 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Among major resistance mutations, 47% of PI-treated patients harbored the L90M mutation, which results from a T A transversion. 2005 Journal of the International AIDS Society Result HIV L90M 74 78 PI 41 43 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Among NNRTI-treated patients, 33.3% harbored the Y181C mutation, which results from a A G transition. 2005 Journal of the International AIDS Society Result HIV Y181C 49 54 NNRTI 6 11 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Another high-prevalence mutation was T215Y (33.3% of patients), which is a result of both C A and A T transversions. 2005 Journal of the International AIDS Society Result HIV T215Y 37 42 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. G190A occurred in 25% of patients (G C) as did V108I (G A). 2005 Journal of the International AIDS Society Result HIV V108I;G190A 47;0 52;5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. In contrast, only 14.7% harbored D30N and 11.7% harbored M46I, both of which result from a G A transition. 2005 Journal of the International AIDS Society Result HIV D30N;M46I 33;57 37;61 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. arguing against a deleterious impact of the R77Q substitution on Vpr functions. 2009 PloS one Result HIV R77Q 44 48 Vpr 65 68 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. As expected, LTNP-04-2 Vpr, containing the Q65R substitution, failed to induce G2-arrest when compared to VprLai. 2009 PloS one Result HIV Q65R 43 47 Vpr 23 26 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Furthermore, a similar phenotype was observed when the R77Q substitution was introduced in VprLai. 2009 PloS one Result HIV R77Q 55 59 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. In addition, Vpr LTNP-04-2 contained the Q65R substitution within the leucine-rich domain of Vpr, recently shown as deleterious for Vpr binding to the DCAF1 subunit of the Cul4a/DDB1 E3 ligase. 2009 PloS one Result HIV Q65R 41 45 Vpr;Vpr;Vpr 13;93;132 16;96;135 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. In contradiction with some reports, we show that the R77Q substitution, found in the sequence of some vpr alleles from LTNPs, does not abolish the pro-apoptotic activity of Vpr. 2009 PloS one Result HIV R77Q 53 57 Vpr;Vpr 102;173 105;176 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Instead, our data suggest that this substitution have a null to moderate positive impact on this activity, in agreement with recent reports showing that introduction of the R77Q mutation in HIV-1NL4-3 Vpr results in a functional protein. 2009 PloS one Result HIV R77Q 173 177 Vpr 201 204 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Interestingly, the Vpr LTNP-04-2 protein, containing the Q65R substitution, as well as the VprLai-GFP Q65R mutant, failed to accumulate at the NE. 2009 PloS one Result HIV Q65R;Q65R 57;102 61;106 Vpr 19 22 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Interestingly, vpr alleles from LTNP-86 and LTNP-04 samples all contained a R77Q substitution, previously reported as deleterious for Vpr proapoptotic activity, whereas LTNP-96 showed an Arg at this position. 2009 PloS one Result HIV R77Q 76 80 Vpr;Vpr 15;134 18;137 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Interestingly, Vpr variants containing the R77Q substitution, namely LTNP-86 and LTNP-04-1, were even slightly more efficient for G-2 arrest and pro-apoptotic activities than those containing an Arg77, including LTNP-96 and PR-1 as well as the prototypic VprLai. 2009 PloS one Result HIV R77Q 43 47 Vpr;PR 15;224 18;226 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Like VprLai and VprLai-R77Q, primary Vpr proteins with an Arg or a Gln similarly bound to these cellular proteins. 2009 PloS one Result HIV R77Q 23 27 Vpr 37 40 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Moreover, PR-3 showed a L64P substitution also described as precluding G2-arrest. 2009 PloS one Result HIV L64P 24 28 PR 10 12 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Moreover, we now report that this mutation, in both a primary Vpr variant and the VprLai Q65R mutant, abrogates Vpr docking at the NE, raising the possibility of a functional link between Vpr accumulation at the NE and its cytostatic activity. 2009 PloS one Result HIV Q65R 89 93 Vpr;Vpr;Vpr 62;112;188 65;115;191 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. One original finding of the present study relies on the identification, in the context of the natural infection, of a Vpr variant harboring the Q65R substitution previously reported as deleterious for DCAF1 binding and consequently for Vpr-induced cell cycle arrest. 2009 PloS one Result HIV Q65R 144 148 Vpr;Vpr 118;236 121;239 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. Regarding the vpr sequences isolated from the progressor patient, PR-2 had a substitution of Ser79 in Gly which is predicted to affect Vpr phosphorylation and its G2-arrest activity. 2009 PloS one Result HIV S79G 93 105 Vpr;Vpr;PR 14;135;66 17;138;68 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. that might be consequent to the presence of the structurally destabilizing L64P mutation, the reduced activity of PR-2 may be related to the S79G substitution, previously shown as deleterious for this activity. 2009 PloS one Result HIV L64P;S79G 75;141 79;145 PR 114 116 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. the Q77R substitution of LTNP-86 and LNTP-04-1 resulted in a slightly reduced ability to induce apoptosis, whereas the R77Q LTNP-96 mutant was more active than the parental variant. 2009 PloS one Result HIV Q77R;R77Q 4;119 8;123 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. To further analyze the influence of the R77Q substitution on the proapoptotic activity of Vpr in the context of the LTNP alleles, we performed a detailed reverse mutational analysis. 2009 PloS one Result HIV R77Q 40 44 Vpr 90 93 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. While no variant had substitution of the Trp54 residue required for UNG2 binding, LTNP-04-2 naturally contained the Q65R substitution and failed to interact with DCAF1, confirming the crucial role of this residue in mediating Vpr/DCAF1 interaction in the context of a primary Vpr variant. 2009 PloS one Result HIV Q65R 116 120 Vpr;Vpr 226;276 229;279 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. Some clade C sequences harbor Ala in place of Asp-278 and numerous clades as well as SIVcpz carry Gly at position 283 (Figure 1); the remaining residues by contrast show little or no sequence variation. 2009 Retrovirology Result HIV D278A 30 53 Asp 46 49 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. The CCD F185K mutation, which dramatically increases the solubility of the HIV-1 protein, was tested in some constructs to assess its potential affects on IN activities in vitro. 2009 Retrovirology Result HIV F185K 8 13 IN 155 157 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. The F185K solubility mutation marginally impacted activity, generally yielding 20-25% reductions when compared to the same protein lacking the CCD change (Figure 3B). 2009 Retrovirology Result HIV F185K 4 9 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. Though others noted that the F185K substitution ablated Mg2+-dependent integration of preprocessed oligonucleotide donor DNA into heterologous target DNA, our reaction conditions failed to reveal an affect of the solubilizing mutation on full-length IN activity in the presence of LEDGFp75 (Figure 5A, lane 6; panels B and C). 2009 Retrovirology Result HIV F185K 29 34 IN 250 252 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. We furthermore conclude that the C-terminal 9 amino acids of HIV-1 IN can be removed without dramatically effecting Mg2+-based single end or concerted DNA integration activities (Figures 3, 4, 5)., We highlight these derivatives as potential candidates for structural biology studies despite the approximate 20-25% reductions in IN1-279 and IN1-276 activities brought on by the F185K change. 2009 Retrovirology Result HIV F185K 378 383 IN 67 69 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Another mutation not associated with drug resistance at position 75 in RT (V75L) was detected first in every subpopulation at week 13 in animal M03250 prior to EFV treatment. 2009 Retrovirology Result HIV V75L 75 79 RT 71 73 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. As in macaque M03250, the V75L and L214F mutations were observed in M04008. 2009 Retrovirology Result HIV L214F;V75L 35;26 40;30 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. At the same time, 6 variants containing K103N (AAC) or K103N (AAT) were detected, which formed 4 subpopulations. 2009 Retrovirology Result HIV K103N;K103N 40;55 45;60 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. At week 17, 81% of subpopulations had the V75L mutation and by week 39, all the subpopulations contained V75L (Additional file 2). 2009 Retrovirology Result HIV V75L;V75L 42;105 46;109 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. At week 39, 5 of 14 subpopulations carried K103N (3 with AAT and 2 with AAC), together accounting for about 35% of the total sequences obtained at week 39 (Additional file 2). 2009 Retrovirology Result HIV K103N 43 48 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. EFV resistance mutations (K103N) initially were observed at week 17, the first sample after EFV monotherapy: an AAC allele (sub5, Figures 3 and 4) and an AAT allele (sub6, Figures 3 and 4). 2009 Retrovirology Result HIV K103N 26 31 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. For example, 5 of the 17 minor subpopulations carried K103N by week 17 (Additional file 2). 2009 Retrovirology Result HIV K103N 54 59 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. For example, only one minor subpopulation with K103N at week 17 (sub7) was present at week 39. 2009 Retrovirology Result HIV K103N 47 52 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. However, none became dominant before the emergence and expansion (to about 75% of the virus population) of the double mutant K103N/M184I (resistant to both EFV and FTC), beginning at week 23 and coincident with the onset of virologic failure. 2009 Retrovirology Result HIV K103N;M184I 125;131 130;136 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. In contrast to macaques M03250 and M04008, only one subpopulation containing V75L was found in M04007 (week 17, 5%) (data not shown), and L214F was not seen at all. 2009 Retrovirology Result HIV L214F;V75L 138;77 143;81 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. In the neighbor joining tree, subpopulations containing K103N(AAC)/K65R or K103N(AAC)/M184I and several others containing K103N(AAC) formed a cluster. 2009 Retrovirology Result HIV K103N;K103N;K103N;K65R;M184I 56;75;122;67;86 61;80;127;71;91 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. In total, 5 of 9 subpopulations contained K103N at week 24, all existing as minor subpopulations. 2009 Retrovirology Result HIV K103N 42 47 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Overall, at week 23, 6 weeks after the initiation of ART, 11 out of 23 subpopulations contained K103N and 4 out of 23 subpopulations contained K65R (3 as K65R/K103N). 2009 Retrovirology Result HIV K103N;K103N;K65R;K65R 96;159;143;154 101;164;147;158 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Several subpopulations containing K103N(AAT) and K103N(AAC) formed another cluster (Figure 1). 2009 Retrovirology Result HIV K103N;K103N 34;49 39;54 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Subpopulations containing the drug resistance mutations K103N (AAC and AAT) formed 5 clusters in the phylogeny (Figure 1 Clusters A-E), indicating that they emerged independently. 2009 Retrovirology Result HIV K103N 56 61 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Subpopulations with a single K103N mutation (without linkage to another drug resistance mutation) were 30% of all viral populations of week 23 (Additional file 1) and none was the dominant subpopulation (Figure 3). 2009 Retrovirology Result HIV K103N 29 34 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The earliest subpopulations containing the EFV resistance mutation K103N were observed at week 17 in both clusters A (AAA to AAC)) and B (AAA to AAT)) and at week 17.5 in clusters C, D, and E (Figure 1). 2009 Retrovirology Result HIV K103N 67 72 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The initial K103N subpopulations in M04008 did not persist, but rather new variants containing K103N appeared and replaced previous subpopulations. 2009 Retrovirology Result HIV K103N;K103N 12;95 17;100 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The same was true at weeks 22 and 23 for a variant carrying two drug resistance mutations: K65R/K103N(AAC) (Figure 3, sub7), encoding resistance to TNF as well as EFV. 2009 Retrovirology Result HIV K103N;K65R 96;91 101;95 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The subpopulation that led to virologic failure in this macaque carried the linked drug resistant mutations K103N(AAC)/M184I. 2009 Retrovirology Result HIV K103N;M184I 108;119 113;124 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The subpopulations containing only K103N were 2.7% of the population at this week, declining from 30.1% at week 23 (Additional file 1), a result of the takeover by the doubly resistant subpopulation 8. 2009 Retrovirology Result HIV K103N 35 40 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Therefore, we used 454 pyrosequencing to increase the sensitivity of detecting the V75L mutation in the viral inoculum. 2009 Retrovirology Result HIV V75L 83 87 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. This data show that V75L emerged after inoculation. 2009 Retrovirology Result HIV V75L 20 24 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Throughout the entire treatment history the dominant subpopulation in M04008 was a wild type virus variant (Figure 5, sub4), although there was an apparent but not statistically significant increase in the overall K103N mutant frequency during the course of treatment. 2009 Retrovirology Result HIV K103N 214 219 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. V75L first appeared at week 13 (Additional file 2) and was found in 79% of subpopulations present at this time point. 2009 Retrovirology Result HIV V75L 0 4 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. We obtained 10,836 pol sequences from the virus challenge stock by 454 pyrosequencing and none contained the V75L mutation (data not shown). 2009 Retrovirology Result HIV V75L 109 113 Pol 19 22 19890215 CYP2C19 genetic variants affect nelfinavir pharmacokinetics and virologic response in HIV-1-infected children receiving highly active antiretroviral therapy. Similarly, there were significant differences in the frequencies of ABCB1-G2677T (P < 0.001) and ABCB1-C1236T genotypes (P < 0.001) in black, non-Hispanic, compared with others. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV C1236T;G2677T 103;74 109;80 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. Crystallographic studies of the inhibitor complexes of G86S and G86S mutants. 2010 Proteins Result HIV G86S;G86S 55;64 59;68 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. Enzymatic activity of G86A/S mutants. 2010 Proteins Result HIV G86A;G86S 22;22 28;28 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. G86S mutation causes more pronounced effects than G86A mutation in solution. 2010 Proteins Result HIV G86A;G86S 50;0 54;4 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. It is plausible that the large change in R87 backbone amide chemical shift is caused by loss of the salt bridge, and as a result, the active site is more flexible or open in the G86A mutant in complex with DMP323. 2010 Proteins Result HIV G86A 178 182 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. NMR studies reveal local structural perturbations caused by G86A mutation. 2010 Proteins Result HIV G86A 60 64 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. Perturbations of the chemical shifts were observed in the entire alpha-helical region (residues 86 to 93) and in the region from residues 64 to 72 in PRG86S/DMP323 as well as around the mutation site, indicating more pronounced conformational changes with the G86S mutation compared to that of G86A. 2010 Proteins Result HIV G86A;G86S;G86S 294;260;152 298;264;156 PR 150 152 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. The G86S mutation produced larger structural changes: the beta-sheet-like interaction of the amide of N88 with the carbonyl oxygen of D29 was greatly weakened by elongation to 3.7 A, and a slight elongation of 0.3 A appeared for the hydrogen bond between the amide of S86 and hydroxyl side chain of T31. 2010 Proteins Result HIV G86S 4 8 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. To understand the chemical shift perturbation caused by G86S mutation in more detail, backbone chemical shifts of PRG86S in the presence of DMP323 were assigned, and compared with those of PR (Figure 3B). 2010 Proteins Result HIV G86S 56 60 PR;PR 114;189 116;191 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. A few peptides within the I34L region had elevated binding to A*0301 (Table 2 and figure 3c) compared to the rest of the I34L peptides, however they did not make the 30% cutoff so additional testing was not carried out. 2010 Journal of immunological methods Result HIV I34L;I34L 26;121 30;125 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. All 50 overlapping 9-mer peptides designed to span the amino acid positions under selective pressure (V7I, I34L, and K403R) in the p17 and p7 region of HIV-1 gag were screened for their ability to bind HLA-A*0301 under optimal conditions (Table 2). 2010 Journal of immunological methods Result HIV I34L;K403R;V7I 107;117;102 111;122;105 Gag 158 161 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. Most of the peptides have a t1/2 less than 1 hour, however AKNCRAPRK (R402K of p7) had the highest stability with a t1/2 of 17.954 hours (Figure 3 and Table 3). 2010 Journal of immunological methods Result HIV R402K 70 76 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. Re-analysis of A*0301 associations with three PS residues identified two more significant associations; V7I (p = 0.0158) and I34L (p = 0.0096) in the p17 region of gag (Table 1) and confirmed previously reported associations of K403R (p = 0.0046) in the p7 region of gag. 2010 Journal of immunological methods Result HIV I34L;K403R;V7I 125;228;104 129;233;107 Gag;Gag 164;267 167;270 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. The K403R region of p7 contained 5 "hits" above 30%: LARNCRAPR (LR9s), AKNCRAPRK (AK9c), ARNCRAPRK (AK9s), KNCRAPRKK (KK9c), and RNCRAPRKK (RK9s) (Figure 1a). 2010 Journal of immunological methods Result HIV K403R 4 9 19903485 Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach. The V7I region of p17 contained two "hits" for A*0301, RASVLSGGK (RAK9c) and RASILSGGK (RAK9s) (Figure 1b). 2010 Journal of immunological methods Result HIV V7I 4 7 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. For lamivudine, at detection of viremia 43% (3/7) had the M184V/I mutation, by 6 months 44% (4/9), by 12 months 57% (8/14), and by 18 months 80% (12/15). 2009 Clinical infectious diseases Result HIV M184I;M184V 58;58 65;65 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Higher weight at cART initiation (p=0.02), modified WHO CD4 failure criteria (p=0.06), and HIV RNA at cART initiation (p=0.03) were associated with a reduced odds of the M184V/I mutation. 2009 Clinical infectious diseases Result HIV M184I;M184V 170;170 177;177 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. In unadjusted analysis, the presence of an NNRTI mutation and the M184V/I mutation at first detection of viremia were both associated with higher HIV RNA at cART initiation (Table 3). 2009 Clinical infectious diseases Result HIV M184I;M184V 66;66 73;73 NNRTI 43 48 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. NNRTI mutations were most common, 42/68 (62%), followed by the M184V/I mutation, 25/68 (37%)(Table 2). 2009 Clinical infectious diseases Result HIV M184I;M184V 63;63 70;70 NNRTI 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Of the patients achieving resuppression despite detectable resistance, all had NNRTI resistance mutations: K103N (8), V106M (5), P225H (1), or G190A (1). 2009 Clinical infectious diseases Result HIV G190A;K103N;P225H;V106M 143;107;129;118 148;112;134;123 NNRTI 79 84 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Results from multivariate modeling for the M184V/I including weight and baseline HIV RNA were as follows: HIV RNA at baseline, compared to < 4.6 log10 c/mL; 4.6-4.9 c/mL, odds ratio (OR) 2.7 (0.64-11); and >4.9 c/mL, OR 5.9 (1.4-26), p trend=0.04; weight per 10kg increase, OR 0.44 (0.23-0.83), p=0.01. 2009 Clinical infectious diseases Result HIV M184I;M184V 43;43 50;50 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Sex, age, CD4 count, NNRTI agent, modified WHO CD4 failure criteria, and WHO stage at cART initiation were not associated with the presence of either NNRTI mutations or the M184V/I mutation (all, p>0.1). 2009 Clinical infectious diseases Result HIV M184I;M184V 173;173 180;180 NNRTI;NNRTI 21;150 26;155 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Delta Cts between mutant and wild-type DNA equivalents were > 10 cycles for the D30N and M184V assays and > 17 cycles for the K103N assays. 2010 AIDS (London, England) Result HIV D30N;K103N;M184V 80;126;89 84;131;94 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. In the multivariate analysis (Table 4), the variables significantly associated with selection of M184V were exposure to dual versus triple-drug PLAT (OR=19.64, 95%CI=2.47-156.25, p<0.01), and duration of zidovudine exposure (OR =1.29, 95%CI=1.03-1.63, p=0.03, per additional month). 2010 AIDS (London, England) Result HIV M184V 97 102 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. In the univariate analysis (Table 3), postpartum detection of the M184V mutation was more likely in women who had all HIV-1 RNA levels > 400 copies/mL during PLAT (OR= 2.65, 95%CI=1.02-6.87, p=0.05) relative to those who remaining aviremic through delivery, and in those with longer exposure to zidovudine (OR=1.25, 95%CI=1.01-1.54, p=0.04, per each additional month). 2010 AIDS (London, England) Result HIV M184V 66 71 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Mutations associated with resistance to nucleoside analogues (NAMs) were also more frequent among women exposed only to dual-drug PLAT (M41L, 5.0%; D67N, 5.0%; K70R, 10.0; and T215Y, 5.0%) than in those treated with 3 drugs (M41L, 1.1%; D67N, 1.1%; K70R, 1.1%; L210F, 1.1%; K219Q, 1.1%). 2010 AIDS (London, England) Result HIV D67N;D67N;K219Q;K70R;K70R;L210F;M41L;M41L;T215Y 148;237;274;160;249;261;136;225;176 152;241;279;164;253;266;140;229;181 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Of note, other factors such as presence of resistance mutations before starting PLAT, the first available CD4+ count during pregnancy, use of hard drugs before delivery, alcoholism before delivery, ethnicity, or age at delivery, were not associated with the postpartum detection of the M184V or K103N mutations. 2010 AIDS (London, England) Result HIV K103N;M184V 295;286 300;291 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. One D30N mutation detected at baseline was not found post-partum. 2010 AIDS (London, England) Result HIV D30N 4 8 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Proportion measurements were linear down to at least 1% for the D30N and M184V assays and to 0.01% for the K103N ASPCR assays. 2010 AIDS (London, England) Result HIV D30N;K103N;M184V 64;107;73 68;112;78 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. The ASPCR testing confirmed the detection of the D30N mutation in one out of 87 women exposed to nelfinavir (1.1% [95% CI: 0.03%-6.24%]) and allowed detection of this mutation in two women out of 27 (7.4%) that did not receive nelfinavir during PLAT. 2010 AIDS (London, England) Result HIV D30N 49 53 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. The M184V mutation, conversely, was less likely to be observed in women who received triple-drug PLAT including either nelfinavir or nevirapine (OR=0.06, 95%CI=0.007-0.44, p=0.006), relative to dual therapy only; in those treated with triple-drug PLAT including nelfinavir (OR=0.06, 95% CI=0.008-0.46, p=0.007) or nevirapine (OR=0.04, 95% CI=0.003-0.48, p=0.01), relative to dual therapy alone; and in those treated with triple-drug PLAT including nelfinavir, relative to any other regimen (OR=0.25, 95%CI=1.01-1.54, p=0.04). 2010 AIDS (London, England) Result HIV M184V 4 9 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Univariate factors associated with postpartum detection of K103N were nevirapine exposure (OR=7.35, 95%CI=1.48-36.5, p=0.01), and longer exposure to zidovudine (OR=1.40, 95%CI=1.02-1.91, p=0.04) or to the combination of zidovudine and lamivudine (OR=1.42, 95%CI=1.04-1.94, p=0.03). 2010 AIDS (London, England) Result HIV K103N 59 64 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Using ASPCR, the K103N mutation was detected in three out of eight women exposed to nevirapine (37.5% [95 CI: 8.5%-75.5%]), including the two cases detected through population sequencing, and in 8 out of 106 women not exposed to nevirapine (7.5%) (p=0.029). 2010 AIDS (London, England) Result HIV K103N 17 22 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Using ASPCR, the K103N mutation was detected postpartum in 1 woman harboring this mutation before treatment and in 2/24 (8.3%) women who did not have this mutation before starting PLAT. 2010 AIDS (London, England) Result HIV K103N 17 22 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Using ASPCR, the M184V mutation was detected postpartum in 2/5 (40%) women with M184V present by population sequencing at baseline and in 15/20 (75%) women who did not have this mutation before treatment. 2010 AIDS (London, England) Result HIV M184V;M184V 17;80 22;85 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Using population sequencing of plasma viruses, the M184V/I mutation was detected postpartum in 65.0% of women receiving dual PLAT throughout pregnancy compared to 28.7% of women treated with 3 drugs (p=0.004). 2010 AIDS (London, England) Result HIV M184I;M184V 51;51 58;58 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Using population sequencing of plasma viruses, the postpartum rates of NNRTI resistance among the eight women receiving nevirapine were: 25% [95% CI: 3.2%-65.1%] for K103N (2 cases), and 12.5%% [95% CI: 0.3%-52.7%] for Y188C (1 case). 2010 AIDS (London, England) Result HIV K103N;Y188C 166;219 171;224 NNRTI 71 76 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Using population sequencing, each of the D30N and L90M mutations were detected in one out of 87 women receiving nelfinavir during PLAT (1.1% [95% CI: 0.03%-6.24%] for each mutation). 2010 AIDS (London, England) Result HIV D30N;L90M 41;50 45;54 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Using the mean plus 3 standard deviations of 20 negative control repeats (wild-type laboratory viral constructs), the detection threshold of the ASPCR was calculated at: 0.1%, 0.4% and 0.003% for the D30N, M184V and K103N ASPCR assays, respectively. 2010 AIDS (London, England) Result HIV D30N;K103N;M184V 200;216;206 204;221;211 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Variables associated with selection of K103N were nevirapine use during pregnancy (OR=9.75, 95%CI=1.62-58.84, p=0.01) and length of dual-PLAT zidovudine + lamivudine exposure (OR =1.46, 95%CI=1.05- 2.02, p=0.02, per additional month). 2010 AIDS (London, England) Result HIV K103N 39 44 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. When including the results from the ASPCR analysis for D30N, M184V and K103N mutations, 72 women (63.2%) had at least 1 resistance mutation detected postpartum, 12 women (10.5%) had dual-class resistance, and 2 (1.7%) women had triple-class resistance after delivery. 2010 AIDS (London, England) Result HIV D30N;K103N;M184V 55;71;61 59;76;66 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Alterations of genetic and mutational barrier to resistance were observed for the most common polymorphism and HLA-B57/*5801-associated T125A as well, described in more detail below. 2009 Antiviral therapy Result HIV T125A 136 141 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Although both changes are single nucleotide step mutations, G193E predicts a reduced mutational barrier to the resistance change according to the Blosum62 scoring matrix, which is based on observed frequencies of different amino acid substitutions over short evolutionary periods in closely related proteins across all natural proteins (E193R score =0 versus G193R score =-2). 2009 Antiviral therapy Result HIV E193R;G193E;G193R 337;60;359 343;65;364 Matrix 163 169 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Although G163E is at the p6 position of the same epitope and is associated with drug resistance and HLA-A*3303 carriage in the reference associations dataset, none of the HLA-A*3303-positive individuals within the study population had G163E (Figure 4). 2009 Antiviral therapy Result HIV G163E;G163E 9;235 14;240 Gag 25 27 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Although the drug resistance change T125K is a minimum single nucleotide exchange, A125K is at least a two-step mutation. 2009 Antiviral therapy Result HIV A125K;T125K 83;36 88;41 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. E157Q at the p1 of the known HLA-A*3303-restricted ER9 epitope (ELKKIIGQVR) is strongly associated with HLA-A*3303 in the reference associations dataset and this was also a significant association within the study dataset (P<0.005). 2009 Antiviral therapy Result HIV E157Q 0 5 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Furthermore, the change required for drug resistance from alanine to lysine (for example, A125K) is scored as a rarely tolerated mutational event (score =-1) in the blosum62 scoring matrix compared with the relatively frequent and therefore permissible exchange between threonine and alanine (for example, T125A; score =0). 2009 Antiviral therapy Result HIV A125K;T125A 90;306 95;311 Matrix 182 188 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. HLA-A*0206 was rare in our study cohorts; however, the only individual carrying this allele had V72I in their autologous integrase sequence. 2009 Antiviral therapy Result HIV V72I 96 100 IN 121 130 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Notably, G193E is an HLA-B*2705-associated polymorphism at p8 of the Epi-pred predicted epitope KRKGGIGGY (Figure 4) and distinct from the resistance change G193R. 2009 Antiviral therapy Result HIV G193E;G193R 9;157 14;162 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Of the 38 major and minor integrase inhibitor resistance associated codons, 44, 61, 66, 92, 121, 140, 143, 147, 148, 155, 226 and 263 were the only positions absolutely conserved across all 342 sequences and these included six primary resistance-associated mutations for raltegravir and elvitegravir (T66I, E92Q, G140S, Y143C/H/R Q148H/R/K and N155S/H). 2009 Antiviral therapy Result HIV E92Q;G140S;N155H;N155S;Q148H;Q148K;Q148R;T66I;Y143C;Y143H;Y143R 307;313;344;344;330;330;330;301;320;320;320 311;318;351;351;339;339;339;305;329;329;329 IN 26 35 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Q148K-G140S double mutants were not detected. 2009 Antiviral therapy Result HIV G140S;Q148K 6;0 11;5 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. T125A association with HLA-B57/*5801 has been observed in several studies and within our subtype-B-infected individuals, 17 individuals carried the HLA-B*5701, 1 carried the HLA-B*5703 and 6 carried the HLA-B*5801 allele. 2009 Antiviral therapy Result HIV T125A 0 5 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. T125A was the most common natural polymorphism at a drug resistance-associated codon in the study. 2009 Antiviral therapy Result HIV T125A 0 5 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. The frequency of T125A differed significantly between subtype B and non-subtype B (21.5% in subtype B and 89.9% in non-subtype B sequences; P<0.001) and was present among a range of non-subtype B subtypes, including A1, C, CRF01, CRF02, CRF06, CRF14 and intersubtype recombinants. 2009 Antiviral therapy Result HIV T125A 17 22 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. The T125A polymorphism was present in 11 (48%) of these 23 individuals compared with 38 (17%) in 220 not carrying the HLA-B57/* 5801 alleles. 2009 Antiviral therapy Result HIV T125A 4 9 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. There were 18 codons at which at least one sequence contained a (non-primary) drug resistance-associated mutation and in nine of these codons, the prevalence of the resistance mutation exceeded 5% in either the SHCS or WAHCS (M50I prevalence 18.0% and 14.8%, V72I 52.2% and 58.8%, T112I 5.6% and 6.3%, S119G 6.2% and 7.3%, K156N 5.7% and 8.0%, G163A/E/Q/T/R 5.1% and 4.4%, V201I 48.1% and 46.8%, T206S 15.6% and 9.3%, and S230N 9.4% and 6.2% for the SHCS and the WAHCS, respectively; Figure 2A). 2009 Antiviral therapy Result HIV G163A;G163E;G163Q;G163R;G163T;K156N;M50I;S119G;S230N;T112I;T206S;V201I;V72I 344;344;344;344;344;323;226;302;422;281;396;373;259 357;357;357;357;357;328;231;307;427;286;401;378;263 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. These seven sites were L74I/M at the C terminus of HLA-B*1510-restricted THLEGKIIL, 91 at p9 of YIEAEVIPA with unknown restriction, T97A at p2 of HLA-A*2601-restricted ETGQETAY, 126 at p9 of HLA-A*3002-restricted KIQNFRYY, 128 at p2 of HLA-A2-restricted AKAACWWAGI, 143 at p9 of HLA-B*1503-restricted KQEFGIPY and 165 at p2 of HLA-A*0205-restricted QVRDQAEHL. 2009 Antiviral therapy Result HIV L74I;L74M;T97A 23;23;132 29;29;136 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Two of these polymorphisms, V72I and V201I, were the most common integrase inhibitor resistance mutations present in pretreatment sequences (Figure 2A) and in both cases, isoleucine was associated with a significantly higher VL than valine (P=0.025, mean delta log10 VL=0.21 at codon 72; P=0.00003, mean delta log10 VL=0.39 at codon 201). 2009 Antiviral therapy Result HIV V201I;V72I 37;28 42;32 IN 65 74 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. V72I is associated with carriage of HLA-A*0206 alleles in population analyses and an HLA-A*0206 epitope (HLEGKVILV) is predicted to span positions 67-75 by the Epi-pred prediction programme. 2009 Antiviral therapy Result HIV V72I 0 4 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. Among NNRTI mutations, Y181C was the predominant, followed by K103N and G190A with similar distribution between groups. 2009 Antiviral therapy Result HIV G190A;K103N;Y181C 72;62;23 77;67;28 NNRTI 6 11 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. In total, 63% in group A and 74% in group B had thymidine analogue mutations (TAMs), with M41L and T215Y significantly (P<0.05) higher in group B (Table 2). 2009 Antiviral therapy Result HIV M41L;T215Y 90;99 94;104 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. K65R was only found among patients failing d4T-containing regimens in both the groups. 2009 Antiviral therapy Result HIV K65R 0 4 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. Overall, 26% of patients in group A and 51%in group B had developed high-level NRTI cross-resistance in terms of coselecting TAMs, K65R and Q151M (Table 2). 2009 Antiviral therapy Result HIV K65R;Q151M 131;140 135;145 NRTI 79 83 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. The frequency of K65R mutation was higher in group B (P=0.10), whereas other nucleoside analogue mutations (NAMs) was evenly distributed. 2009 Antiviral therapy Result HIV K65R 17 21 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. At 48 hours, cells were fixed and examined by confocal microscopy As shown in Figure 3, VpuEGFP or VpuL63AEGFP were predominantly localized in intracellular compartments, suggesting that the L63A mutation did not drastically alter its intracellular expression in cells. 2010 Virology Result HIV L63A 191 195 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. L63A, V68A mutants have a slower turnover in transfected 293 cells. 2010 Virology Result HIV V68A;L63A 6;0 10;4 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Vpu L63A but not V68A affects CD4 degradation. 2010 Virology Result HIV L63A;V68A 4;17 8;21 Vpu 0 3 19949656 Antiretroviral genotypic resistance mutations in HIV-1 infected Korean patients with virologic failure. M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (17/41, 41.5%) and M46I/L (14/41, 34.2%). 2009 Journal of Korean medical science Result HIV M184I;M184V;M46I;M46L;T215F;T215Y 0;0;92;92;65;65 7;7;98;98;72;72 19949656 Antiretroviral genotypic resistance mutations in HIV-1 infected Korean patients with virologic failure. M41L, I54V, D30N, and V82A/T/S were observed in more than 10 patients and K103N (10/41, 24.4%) was the most frequently observed NNRTI associated mutation. 2009 Journal of Korean medical science Result HIV D30N;I54V;K103N;V82A;V82S;V82T;M41L 12;6;74;22;22;22;0 16;10;79;30;30;30;4 NNRTI 128 133 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Although it is common for M184V mutations to be selected along with TAMs in subjects failing on regimens containing zidovudine and lamivudine, in this study a relatively small number of subjects had virus with M184V at VF (3/14 by PG, 7/14 by CG). 2010 The Journal of antimicrobial chemotherapy Result HIV M184V;M184V 26;210 31;215 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. At baseline, Subject 5 had viral clones containing K103N with or without T215A, or with Y188L resistance mutations, while at VF clones with one or more of the following mutations: M41L, D67N, K70R, M184V, Y188L, T215F or L, and K219E were detected, but K103N and T215A were not. 2010 The Journal of antimicrobial chemotherapy Result HIV D67N;K103N;K103N;K219E;K70R;M184V;M41L;T215A;T215A;T215F;Y188L;Y188L 186;51;253;228;192;198;180;73;263;212;88;205 190;56;258;233;196;203;184;78;268;217;93;210 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. At failure, virus from five of these seven subjects contained TAMs with or without M184V (Subjects 5, 8, 9, 10 and 14) or K65R (Subject 2). 2010 The Journal of antimicrobial chemotherapy Result HIV K65R;M184V 122;83 126;88 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. At VF, Subject 1 population sequencing revealed only K65K/R, and only clones with the K65R mutation were observed at the first timepoint (with or without Y115F and S68 mutations), but at the later timepoint TAM-containing clones (one clone with D67N + L210W + T215F and another clone with T215A) were also detected in addition to K65R-containing clones. 2010 The Journal of antimicrobial chemotherapy Result HIV D67N;K65K;K65R;K65R;K65R;L210W;T215A;T215F;Y115F 245;53;53;86;330;252;289;260;154 249;59;59;90;334;257;294;265;159 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. By PG at VF, virus from seven subjects had selected for TAMs or for TAMs plus an M184V mutation. 2010 The Journal of antimicrobial chemotherapy Result HIV M184V 81 86 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. For example, Subjects 5 and 9 had HIV with T215A reversion mutations at baseline, but not at VF (where T215F was detected in virus from both subjects). 2010 The Journal of antimicrobial chemotherapy Result HIV T215A;T215F 43;103 48;108 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. For Subject 2, K70E was detected by CG at baseline, followed by selection of K65R at failure. 2010 The Journal of antimicrobial chemotherapy Result HIV K65R;K70E 77;15 81;19 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. However, when analysed by CG, low-abundance viral species containing resistance mutations were detected in three of these four subjects at VF (L210W for Subject 8, Y188L for Subject 12 and M184I for Subject 13). 2010 The Journal of antimicrobial chemotherapy Result HIV L210W;M184I;Y188L 143;189;164 149;194;169 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. In 6/7 of these subjects, CG revealed additional TAMs or M184V that were not detected by PG. 2010 The Journal of antimicrobial chemotherapy Result HIV M184V 57 62 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. In the remaining subject (Subject 5), 5/6 TAMs plus M184V were already detected by PG at VF. 2010 The Journal of antimicrobial chemotherapy Result HIV M184V 52 57 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Interestingly, although Subject 8 had low-abundance viral species containing the L210W mutation by VF, a different TAM (K219Q) had been detected at baseline by CG. 2010 The Journal of antimicrobial chemotherapy Result HIV K219Q;L210W 120;81 125;86 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Interestingly, Subject 2 also had viral clones with M184V alone at baseline; however, M184V was not detected at failure. 2010 The Journal of antimicrobial chemotherapy Result HIV M184V;M184V 52;86 57;91 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Interestingly, when utilizing the more sensitive method of clonal analysis, at the last study visit examined by CG four of the VF subjects had virus with TAMs but no viral clones that also contained the M184V mutation (Subjects 1, 4, 8 and 14). 2010 The Journal of antimicrobial chemotherapy Result HIV M184V 203 208 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K103R, Y181H and G190E) from archived drug-resistant virus were also detected in some baseline samples by CG. 2010 The Journal of antimicrobial chemotherapy Result HIV G190E;Y181H;K103R 17;7;0 22;12;5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Mutations detected by CG at baseline that could have impacted response to one or more study drugs included mutations at T215, K70E, D67G, M184V and the multi-NRTI Q151M-associated mutations A62V and F77L. 2010 The Journal of antimicrobial chemotherapy Result HIV A62V;D67G;F77L;K70E;M184V;Q151M 190;132;199;126;138;163 194;136;203;130;143;168 NRTI 158 162 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Seven of the VF subjects at baseline had resistance mutation-containing low-abundance viral species (including one of more of the following: A62V, F77L, K70E, T215A, T215S, D67G, M184V or K219Q) with the potential to impact response to one or more study drugs. 2010 The Journal of antimicrobial chemotherapy Result HIV A62V;D67G;F77L;K219Q;K70E;M184V;T215A;T215S 141;173;147;188;153;179;159;166 145;177;151;193;157;184;164;171 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The L210W and M184I mutations were treatment emergent for Subjects 8 and 13, respectively, while the NNRTI mutation Y188L that was observed by CG at VF for Subject 12 had also been detected at baseline by CG (but not by PG). 2010 The Journal of antimicrobial chemotherapy Result HIV L210W;M184I;Y188L 4;14;116 9;19;121 NNRTI 101 106 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The only subject with TAMs detected at baseline who did not have detectable TAMs at failure was Subject 6, who had only a very low incidence of T215S (1/128 clones) at baseline. 2010 The Journal of antimicrobial chemotherapy Result HIV T215S 144 149 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The T215F variant was much more commonly detected than T215Y. 2010 The Journal of antimicrobial chemotherapy Result HIV T215F;T215Y 4;55 9;60 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The Y188L NNRTI mutation and unusual amino acid mutations at NNRTI resistance sites that might reflect reversion of NNRTI mutations (e.g. 2010 The Journal of antimicrobial chemotherapy Result HIV Y188L 4 9 NNRTI;NNRTI;NNRTI 10;61;116 15;66;121 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Two subjects with baseline wild-type virus by PG selected for the K65R mutation at VF. 2010 The Journal of antimicrobial chemotherapy Result HIV K65R 66 70 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. No polymorphisms overlapped with the list of PRAMs; however, 87 (10%) sequences contained one or more PRAMs (median = 2, range = 1-4), with L90M encountered most frequently (3.6%), and 47 sequences (5.3% of total) harbored more than 1 PRAM, with 50 (5.7%) sequences being resistant to protease inhibitor. 2010 AIDS (London, England) Result HIV L90M 140 144 PR 285 293 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. There were six differences between the consensus sequence inferred from our dataset and the subtype B consensus sequence (I13V, E35D, M36I, R41K, H69K and L89M). 2010 AIDS (London, England) Result HIV E35D;H69K;I13V;L89M;M36I;R41K 128;146;122;155;134;140 132;150;126;159;138;144 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. Q151M and L74V were found in 7 (18%) and 2 (5%), respectively. 2009 AIDS research and therapy Result HIV L74V;Q151M 10;0 14;5 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. The frequencies of thymidine analogue associated mutations (TAMs) were 17 (43%) D67N, 16 (40%) T215FY, 8 (20%) M41L, 6 (15%) K60R, 6 (15%) L210W, 2 (5%) K219Q. 2009 AIDS research and therapy Result HIV D67N;K219Q;K60R;L210W;M41L;T215F;T215Y 80;153;125;139;111;95;95 84;158;129;144;115;101;101 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Additionally, double substitutions at positions 162 and 170 (D163A-N170R) were engineered in a single molecule. 2010 Immunology letters Result HIV D163A;N170R 61;67 66;72 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Consistent with this report, Envgp120 fused to C3d D163A and N170R had a reduced, albeit not significantly, binding affinity for sCR2 (30% and 60% reduction, respectively). 2010 Immunology letters Result HIV D163A;N170R 51;61 56;66 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Envgp120-C3d2 with wild-type and individual mutant C3d proteins (R162A, D163A, N170R) were tested for the binding affinity to immobilized murine sCR2. 2010 Immunology letters Result HIV D163A;N170R;R162A 72;79;65 77;84;70 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. In the murine C3d, however, the R162A mutation neither impaired nor enhanced the binding affinity for sCR2 compared to wild-type C3d. 2010 Immunology letters Result HIV R162A 32 37 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Interestingly, similar to the binding assay results, the combined mutations at residues 162 and 170 (Envgp120-C3d2 D163A-N170R) reduced the anti-Env titers by 87% (1:200). 2010 Immunology letters Result HIV N170R;D163A 121;115 126;120 Env 145 148 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Mutation K162A in the human C3d molecule was reported to enhance the binding avidity of C3d for CR2. 2010 Immunology letters Result HIV K162A 9 14 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Mutations D163A and N170R have both been reported to reduce the binding affinity for CR2 in the human molecules. 2010 Immunology letters Result HIV D163A;N170R 10;20 15;25 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. There was a significant reduction on the binding affinity of the double mutant D163A-N170R for sCR2 (90% reduction) (p<0.05). 2010 Immunology letters Result HIV D163A;N170R 79;85 84;90 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. These substitutions included an R for A substitution at residue 162 (R162A), D for A at position 163 (D163A) and N for R at residue 170 (N170R). 2010 Immunology letters Result HIV A162R;A163D;D163A;N170R;R162A;R170N 32;77;102;137;69;113 67;100;107;142;74;135 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. As expected, HIV-1 Vpu S52A replicated as efficiently as WT HIV-1 in cultures of primary blood lymphocytes, whereas Vpu-defective HIV-1 showed attenuated and delayed replication kinetics (Additional file 3. 2010 Retrovirology Result HIV S52A 23 27 Vpu;Vpu 19;116 22;119 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. At these levels of tetherin expression the S52A Vpu enhanced p24 release as efficiently as the wildtype Vpu protein. 2010 Retrovirology Result HIV S52A 43 47 p24;Vpu;Vpu 61;48;104 64;51;107 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Expression of wildtype Vpu resulted in about 50% reduction in the number of tetherin expressing cells, whereas the S52A Vpu degraded tetherin in only about 20% of cells. 2010 Retrovirology Result HIV S52A 115 119 Vpu;Vpu 23;120 26;123 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. For functional analyses, we generated untagged and AU1-tagged forms of the wildtype and S52A HIV-1 NL4-3 Vpus and verified their expression by Western blot analysis. 2010 Retrovirology Result HIV S52A 88 92 Vpu 105 109 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Furthermore, electroporation of Jurkat T-cells with the proviral constructs and increasing amounts of tetherin expression plasmids confirmed that in T-cells the ability of Vpu S52A to enhance HIV-1 release also decreases in a tetherin-expression dependent manner (Additional file 3. 2010 Retrovirology Result HIV S52A 176 180 Vpu 172 175 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Furthermore, the levels of cell surface tetherin in infected cells expressing S52A Vpu were significantly lower than in cells infected with HIV-1 containing an entirely defective vpu gene. 2010 Retrovirology Result HIV S52A 78 82 Vpu;Vpu 83;179 86;182 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. In contrast, the S52A Vpu was inactive in both assays. 2010 Retrovirology Result HIV S52A 17 21 Vpu 22 25 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. In sum, the S52A change severely attenuates the ability of Vpu to enhance HIV-1 release with increasing levels of tetherin expression. 2010 Retrovirology Result HIV S52A 12 16 Vpu 59 62 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Individual or combined deletions in nef and vpu significantly reduced CD4+ T-cell depletion irrespectively of the viral coreceptor tropism, whereas the S52A mutation in Vpu had no significant effect. 2010 Retrovirology Result HIV S52A 152 156 Nef;Vpu;Vpu 36;44;169 39;47;172 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Moreover, the S52A change as well as inactivation of Vpu impaired the ability of HIV-1 to down-modulate CD4 to the same extent. 2010 Retrovirology Result HIV S52A 14 18 Vpu 53 56 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Moreover, Vpu as well as the S52A mutant had similar minor effects on the levels of cell surface tetherin in MDM. 2010 Retrovirology Result HIV S52A 29 33 Vpu 10 13 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Most importantly, these findings demonstrated that the S52A Vpu is capable of enhancing virion release from HeLa derived P4-CCR5 cells that express relatively low levels of tetherin. 2010 Retrovirology Result HIV S52A 55 59 Vpu 60 63 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Most remarkably, the S52A mutation in Vpu impaired the replicative capacity of HIV-1 in macrophages as severely as the complete lack of Vpu function. 2010 Retrovirology Result HIV S52A 21 25 Vpu;Vpu 38;136 41;139 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. The latter constructs were generated because Nef is known to down-modulate CD4 and to enhance viral infectivity and replication and may thus bias possible effects of the S52A change in Vpu. 2010 Retrovirology Result HIV S52A 170 174 Nef;Vpu 45;185 48;188 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. The S52A change in Vpu impairs HIV-1 replication in macrophages. 2010 Retrovirology Result HIV S52A 4 8 Vpu 19 22 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. The S52A mutation in Vpu does not impair HIV-1 replication and cytopathicity in lymphoid tissue ex vivo. 2010 Retrovirology Result HIV S52A 4 8 Vpu 21 24 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. The S52A Vpu enhanced the release of progeny virions with similar efficiency, whereas Nef had no significant effect. 2010 Retrovirology Result HIV S52A 4 8 Nef;Vpu 86;9 89;12 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. The S52A Vpu is only able to antagonize tetherin at low expression levels. 2010 Retrovirology Result HIV S52A 4 8 Vpu 9 12 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Therefore, the wildtype like phenotype of HIV-1 Vpu S52A in HLT might be due to low tetherin expression levels in the relevant HIV-1 tissue target cells. 2010 Retrovirology Result HIV S52A 52 56 Vpu 48 51 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Therefore, we speculated that Vpu S52A might be able to enhance HIV-1 release at low levels of tetherin expression. 2010 Retrovirology Result HIV S52A 34 38 Vpu 30 33 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. These results show that mutation of S52A is sufficient to entirely disrupt the effect of Vpu on CD4 and establish at a single cell level that an intact CK-II phosphorylation site as well as active CK-II are important for degradation of tetherin by Vpu. 2010 Retrovirology Result HIV S52A 36 40 Vpu;Vpu 89;248 92;251 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. This result was in line with our hypothesis that Vpu S52A can overcome relatively low levels of tetherin expression, because our P4-CCR5 cells expressed tetherin in a range comparably to unstimulated PBMCs (Additional file 2). 2010 Retrovirology Result HIV S52A 53 57 Vpu 49 52 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Thus, Vpu S52A down-modulates tetherin from HIV-1 infected T-cells, albeit with lower efficiency than wildtype Vpu. 2010 Retrovirology Result HIV S52A 10 14 Vpu;Vpu 6;111 9;114 HIV infections 44 58 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Thus, Vpu S52A might be differentially active in the enhancement of particle release from primary T-cells and monocyte-derived macrophages (MDM) because it is only able to counteract tetherin at low expression levels. 2010 Retrovirology Result HIV S52A 10 14 Vpu 6 9 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Thus, Vpu S52A might be impaired in the enhancement of particle release from infected MDM, because it is not able to counteract tetherin at high expression levels. 2010 Retrovirology Result HIV S52A 10 14 Vpu 6 9 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Thus, we finally wanted to challenge the hypothesis that Vpu S52A might be impaired in the enhancement of particle release from infected MDM, because it is not able to counteract high tetherin expression levels. 2010 Retrovirology Result HIV S52A 61 65 Vpu 57 60 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. To investigate the effect of the S52A mutation in Vpu on HIV-1 release we constructed CXCR4(X4)- and CCR5(R5)-tropic HIV-1 NL4-3 mutants carrying this change alone or in combination with a disrupted nef gene. 2010 Retrovirology Result HIV S52A 33 37 Nef;Vpu 199;50 202;53 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. To study the effect of the S52A change in Vpu on HIV-1 replication and cytopathicity, we infected HLT ex vivo with the X4 and R5 NL4-3 variants. 2010 Retrovirology Result HIV S52A 27 31 Vpu 42 45 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. To test whether the S52A change affects tetherin degradation by Vpu, we generated an N-terminally eCFP-tagged version of tetherin. 2010 Retrovirology Result HIV S52A 20 24 Vpu 64 67 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Vpu S52A impairs tetherin and CD4 degradation in transfected 293T cells. 2010 Retrovirology Result HIV S52A 4 8 Vpu 0 3 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Vpu S52A promotes virus release from HeLa-derived cells. 2010 Retrovirology Result HIV S52A 4 8 Vpu 0 3 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Vpu S52A still degraded tetherin to some extent in cells co-transfected with Vpu and tetherin expression plasmids (Figures 1D and 1E). 2010 Retrovirology Result HIV S52A 4 8 Vpu;Vpu 0;77 3;80 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. We co-transfected 293T cells with WT, Vpu-defective, and Vpu S52A expressing proviral constructs and different amounts of tetherin ranging from 100 ng (1:50; ratio transfected tetherin:provirus) to 10 ng (1:500); and we measured cellular as well as released p24 by a quantitative Western blot two days later. 2010 Retrovirology Result HIV S52A 61 65 p24;Vpu;Vpu 258;38;57 261;41;60 20096702 A dynamic model of HIV integrase inhibition and drug resistance. 4-5, our models predict a marked reduction in conformational flexibility for the G140S/Q148H mutant. 2010 Journal of molecular biology Result HIV G140S;Q148H 81;87 86;92 20096702 A dynamic model of HIV integrase inhibition and drug resistance. 8) likely affected the observed differences in raltegravir accessibility between the wild type and G140S/Q148H mutant. 2010 Journal of molecular biology Result HIV G140S;Q148H 99;105 104;110 20096702 A dynamic model of HIV integrase inhibition and drug resistance. A similar relationship exists between G140S and mutations at Q148, where G140S appears to mitigate, in part, the fitness loss associated with Q148 mutations. 2010 Journal of molecular biology Result HIV G140S;G140S 38;73 43;78 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Consequently, the new modeling protocol was applied to three different variants of the catalytic core domain of HIV integrase: the wild type, the E92Q/N155H drug-resistant mutant, and the G140S/Q148H drug-resistant mutant. 2010 Journal of molecular biology Result HIV E92Q;G140S;N155H;Q148H 146;188;151;194 150;193;156;199 IN 116 125 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Conversely, the E92Q/N155H mutant displayed much more flexibility in the 140s loop than the wild type, as reflected in the RMSD trends displayed in. 2010 Journal of molecular biology Result HIV E92Q;N155H 16;21 20;26 20096702 A dynamic model of HIV integrase inhibition and drug resistance. During clinical studies of raltegravir, three pathways to resistance have been observed involving residues N155H, Q148H/K/R, and Y143C/R. 2010 Journal of molecular biology Result HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 107;114;114;114;129;129 112;123;123;123;136;136 20096702 A dynamic model of HIV integrase inhibition and drug resistance. E92Q has been shown to enhance the raltegravir resistance associated with N155H when both appear on the same clone. 2010 Journal of molecular biology Result HIV N155H;E92Q 74;0 79;4 20096702 A dynamic model of HIV integrase inhibition and drug resistance. E92Q is associated with resistance to both raltegravir and elvitegravir. 2010 Journal of molecular biology Result HIV E92Q 0 4 20096702 A dynamic model of HIV integrase inhibition and drug resistance. In the full ensemble of G140S/Q148H mutant targets, only 3 of the 52 mutant conformations (i.e., 6%) produced the primary binding mode. 2010 Journal of molecular biology Result HIV G140S;Q148H 24;30 29;35 20096702 A dynamic model of HIV integrase inhibition and drug resistance. It is important to note that the G140S and Q148H mutations are present in the 140s loop, unlike the E92Q and N155H mutations, which are part of the predicted drug-binding site. 2010 Journal of molecular biology Result HIV E92Q;G140S;N155H;Q148H 100;33;109;43 104;38;114;48 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Possibly as a consequence of this increased fitness, over longer periods of therapy, viruses containing G140S/Q148H tend to expand to replace other resistance mutations, even where the E92Q/N155H mutation has previously predominated. 2010 Journal of molecular biology Result HIV E92Q;G140S;N155H;Q148H 185;104;190;110 189;109;195;115 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Raltegravir's predicted binding mode against the G140S/Q148H mutant is displayed in. 2010 Journal of molecular biology Result HIV G140S;Q148H 49;55 54;60 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Representative ensembles of conformations of the wild type and G140S/Q148H mutant were utilized in docking experiments with AutoDock4. 2010 Journal of molecular biology Result HIV G140S;Q148H 63;69 68;74 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Since N155H is a primary mutation that confers raltegravir-resistance in clinical trials, properly modeling the dynamic interactions that control the orientation of residue 155 is very important. 2010 Journal of molecular biology Result HIV N155H 6 11 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Since one of the most raltegravir-resistant mutants involves replacing one of the flanking glycine residues with a much more constrained serine residue (i.e., G140S), it is reasonable to expect this mutant to display different structural preferences in the dynamics of its 140s loop. 2010 Journal of molecular biology Result HIV G140S 159 164 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Since this side-chain has flipped in the G140S/Q148H mutant system, only the N atom of H67's side-chain is near raltegravir. 2010 Journal of molecular biology Result HIV G140S;Q148H 41;47 46;52 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The binding mode raltegravir displayed against the G140S/Q148H mutant is similar to the primary mode that it displayed against the wild type, but this mode was produced by a much smaller percentage of the mutant's conformations. 2010 Journal of molecular biology Result HIV G140S;Q148H 51;57 56;62 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The G140S/Q148H mutant displayed a much tighter distribution of the distance between the beta carbons of residues 148 and 152 than the other two systems [data not shown]. 2010 Journal of molecular biology Result HIV G140S;Q148H 4;10 9;15 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The RMSD data agreed with the other types of measurements, which indicated the G140S/Q148H mutant displayed very little variation in the conformation of the 140s loop during MD. 2010 Journal of molecular biology Result HIV G140S;Q148H 79;85 84;90 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The wild type's MD simulation displayed a moderate amount of flexibility in this critical loop, while the E92Q/N155H mutant displayed much more dynamic flexibility than the other two systems. 2010 Journal of molecular biology Result HIV E92Q;N155H 106;111 110;116 20096702 A dynamic model of HIV integrase inhibition and drug resistance. This hypothesis agrees well with the observation that, under raltegravir selection pressure, E92Q/N155H and G140S/Q148H are selected independently and most likely employ different, mutually exclusive mechanisms to resist raltegravir. 2010 Journal of molecular biology Result HIV E92Q;G140S;N155H;Q148H 93;108;98;114 97;113;103;119 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. A post-hoc analysis of the baseline characteristics of subjects with low-abundance Y181C mutants in the randomly sampled subcohort showed no differences between virologic failures and non-failures regarding screening HIV-1 RNA levels, CD4+ T-cell counts, or race/ethnicity (not shown). 2010 The Journal of infectious diseases Result HIV Y181C 83 88 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. A significant association with the detection of minority K103N mutants and an increased risk of virologic failure was not detected (P=0.22), but the direction of the effect was similar (HR=1.58, 95% CI=0.76, 3.28). 2010 The Journal of infectious diseases Result HIV K103N 57 62 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Among adherent subjects, the presence of minority Y181C by ASPCR had an increased risk of virologic failure compared to those that were sensitive by both population sequencing and ASPCR (HR=3.45, 95% CI= 1.90, 6.26; P<0.001); among non-adherent subjects, the presence of minority Y181C did not show a significantly increased risk of virologic failure (HR=1.39, 95% CI= 0.58, 3.29, P=0.46). 2010 The Journal of infectious diseases Result HIV Y181C;Y181C 50;280 55;285 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Among subjects in the random cohort with available sequencing and day 14 viral load data, the mean change in viral load at day 14 on study from baseline was not significantly different between subjects with low-abundant Y181C and subjects with no NNRTI resistance mutations (P=0.97); a significantly smaller mean change in viral load at day 14 from baseline was detected in subjects with bulk resistance (mean change=-1.53 log 10copies/mL) as compared to subjects with no NNRTI resistance mutations (mean change=-2.06 log 10copies/mL) (difference: 0.52, 95% CI=0.13,0.91 copies/mL, P=0.01). 2010 The Journal of infectious diseases Result HIV Y181C 220 225 NNRTI;NNRTI 247;472 252;477 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Among subjects in the random subcohort in whom minority NNRTI-resistant variants were detected, the median (interquartile range) levels of mutants were: K103N, AAC allele= 0.012% (0.008%-0.116%); K103N, AAT allele= 0.013% (0.005%-0.053%); and Y181C=0.060% (0.048%-0.089%). 2010 The Journal of infectious diseases Result HIV K103N;K103N;Y181C 153;196;243 158;201;248 NNRTI 56 61 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Among subjects with wild-type HIV-1 by population sequencing, detection of low-abundance Y181C mutants by ASPCR was associated with an increased risk of virologic failure (HR=2.54, 95% CI= 1.53, 4.20). 2010 The Journal of infectious diseases Result HIV Y181C 89 94 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. As previously reported, the prevalence of pre-treatment NNRTI resistance by population sequencing in the randomly sampled subcohort was 5%; this included 6 subjects with K103N alone, 2 with K103N together with a second NNRTI resistance mutation (other than Y181C), 0 with Y181C alone, and 1 with both K103N and Y181C by population sequencing at baseline. 2010 The Journal of infectious diseases Result HIV K103N;K103N;K103N;Y181C;Y181C;Y181C 170;190;301;257;272;311 175;195;306;262;277;316 NNRTI;NNRTI 56;219 61;224 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Detection thresholds were: K103N (AAC) = 0.003%, K103N (AAT) = 0.001% and Y181C = 0.03%. 2010 The Journal of infectious diseases Result HIV K103N;K103N;Y181C 27;49;74 32;54;79 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Following these observations we chose to examine whether low-abundant Y181C mutants impacted initial declines (to day 14) in HIV-1 RNA level upon treatment initiation. 2010 The Journal of infectious diseases Result HIV Y181C 70 75 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Further modeling suggested an interaction between baseline presence of low-abundance Y181C mutants and recent adherence (P=0.08), showing that in the presence of recent non-adherence, the effect of minority Y181C was diminished (Figure 4). 2010 The Journal of infectious diseases Result HIV Y181C;Y181C 85;207 90;212 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. In exploratory analyses, we were unable to define a threshold level of Y181C mutants that distinguished failures and non-failures with high sensitivity and specificity (not shown). 2010 The Journal of infectious diseases Result HIV Y181C 71 76 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. K103N minority mutants were as frequent in non-failures as failures in the random subcohort with respect to Y181C minority mutants (Figure 3). 2010 The Journal of infectious diseases Result HIV Y181C;K103N 108;0 113;5 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Low-abundance K103N and/or Y181C mutants and virologic failure. 2010 The Journal of infectious diseases Result HIV K103N;Y181C 14;27 19;32 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Low-abundant K103N and/or Y181C mutants and viral dynamics. 2010 The Journal of infectious diseases Result HIV K103N;Y181C 13;26 18;31 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. No resistance mutations were detected in 27 (41.5%), K103N was detected in 25 (38.5%), Y181C in 5 (7.7%) and K101E in 4 (6.2%); 2 of these 4 [3.1%] also had the K103N mutation (Table 2). 2010 The Journal of infectious diseases Result HIV K101E;K103N;K103N;Y181C 109;53;161;87 114;58;166;92 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Note, an additional 4 subjects had only ASPCR data for K103N or Y181C, but not both (2 and 2, respectively). 2010 The Journal of infectious diseases Result HIV K103N;Y181C 55;64 60;69 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Of note, the levels of Y181C and K103N mutants detected in individual samples were all below 1% (Figure 2 and data not shown). 2010 The Journal of infectious diseases Result HIV K103N;Y181C 33;23 38;28 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Of the 183 subjects assayed for the presence of pre-existing low-abundance K103N and/or Y181C mutants using ASPCR, variants carrying the K103N, Y181C, or both were detected in 8 (4.4%), 54 (29.5%) and 11 (6%) subjects, respectively. 2010 The Journal of infectious diseases Result HIV K103N;K103N;Y181C;Y181C 75;137;88;144 80;142;93;149 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Of the 185 subjects in the random subcohort, 58% of virologic failures compared to 29% of non-failures had low-abundance Y181C mutants at baseline (P=0.001). 2010 The Journal of infectious diseases Result HIV Y181C 121 126 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Pre-existing low-abundance K103N mutants were detected less often than Y181C variants. 2010 The Journal of infectious diseases Result HIV K103N;Y181C 27;71 32;76 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Similar results were obtained when repeating this analysis using the presence of any minority variant (either K103N or Y181C) (data not shown). 2010 The Journal of infectious diseases Result HIV K103N;Y181C 110;119 115;124 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Sixty-five subjects with low-abundance Y181C mutants at baseline experienced virologic failure and had a viral genotype (by population sequencing) available at the time of virologic failure. 2010 The Journal of infectious diseases Result HIV Y181C 39 44 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. The relative prevalence of Y181C mutants in subjects with virologic failure compared to subjects without virologic failure was similar across subgroups defined by presence or absence of the K103N mutation, assignment to the 4-drug or 3-drug arm, and screening HIV-1 RNA level (Figure 3). 2010 The Journal of infectious diseases Result HIV K103N;Y181C 190;27 195;32 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. A significant association was found between NNRTI-experience and Y181C variants at mutant cutoff frequencies >0.5% (5/22 versus 3/72, P=0.016) and >1% (5/22 versus 3/72, P=0.016). 2010 The Journal of infectious diseases Result HIV Y181C 65 70 NNRTI 44 49 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. A trend for association was found between NNRTI-experience and K103N at frequencies >0.5% (4/24 versus 4/71, P = 0.11) and >1% (3/24 versus 2/7, P = 0.10). 2010 The Journal of infectious diseases Result HIV K103N 63 68 NNRTI 42 47 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. By contrast, baseline sequences from NNRTI-naive subject 5N and 12N containing P225H and L100I, respectively, did not cluster with the predominant resistant variants at failure (Fig 2B-C). 2010 The Journal of infectious diseases Result HIV L100I;P225H 89;79 94;84 NNRTI 37 42 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. By contrast, Y181C variants were not significantly associated with either protocol-defined virologic failure or change in HIV-1 RNA from entry to week 24 (table 2), although the average reduction in HIV-1 was lower for those with >1% Y181C (-0.4 log10 copies/ml) versus those with <=1.0% mutant (-1.1 log10 copies/ml). 2010 The Journal of infectious diseases Result HIV Y181C;Y181C 13;234 18;239 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. For NNRTI-experienced subject 3E, entry sequences containing K101E showed a trend toward clustering (bootstrap value 46) with failure sequences containing L100I/K101E/Y188L or L100I/K101E/G190A (figure 2E). 2010 The Journal of infectious diseases Result HIV G190A;K101E;K101E;L100I;L100I;Y188L;K101E 188;161;182;155;176;167;61 193;166;187;160;181;172;66 NNRTI 4 9 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. In addition, allele-specific PCR could not be obtained in 4 subjects for Y181C and 3 for K103N, leaving 95 subjects evaluated for K103N and 94 for Y181C (table 2). 2010 The Journal of infectious diseases Result HIV K103N;K103N;Y181C;Y181C 89;130;73;147 94;135;78;152 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. In subject 7N from the NNRTI-naive group (Fig 2A), a baseline sequence containing K103N clustered closely (bootstrap value 96) with sequences at failure containing K103N linked to Y188C or M230L. 2010 The Journal of infectious diseases Result HIV K103N;K103N;M230L;Y188C 82;164;189;180 87;169;194;185 NNRTI 23 28 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. K103N at >0.5% frequency was also significantly associated with inferior HIV-1 RNA response, although the strength of association was lower (P = 0.006). 2010 The Journal of infectious diseases Result HIV K103N 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. K103N at frequencies >1.0% was strongly associated with inferior HIV-1 RNA response from baseline to week 24 by intent-to-treat (ITT) analysis (P <0.001; table 2). 2010 The Journal of infectious diseases Result HIV K103N 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. K103N at frequencies >1% was also associated with protocol-defined virologic failure in both on-treatment (P = 0.036) and ITT analyses (P = 0.053). 2010 The Journal of infectious diseases Result HIV K103N 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. NNRTI-experienced subject 5E had two distinct populations of sequences at entry, one wildtype and one containing several linked NNRTI-resistance mutations (K101E/Y181C/G190A). 2010 The Journal of infectious diseases Result HIV G190A;K101E;Y181C 168;156;162 173;161;167 NNRTI;NNRTI 0;128 5;133 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. Specifically, K103N >1.0% was associated with a rise in HIV-1 RNA of 0.5 log10 copies/ml, whereas K103N <=1.0% was associated with a decrease in HIV-1 RNA of 1.1 log10 copies/ml. 2010 The Journal of infectious diseases Result HIV K103N;K103N 14;98 19;103 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. To 13 illustrate, patient 8E had sequences at entry and failure containing K103N, but these were not closely related (figure 2F). 2010 The Journal of infectious diseases Result HIV K103N 75 80 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. To further assess if minor populations of NNRTI-resistant variants were more frequent in the NNRTI-experienced patients and associated with virologic failure, baseline samples from 103 subjects (76 NNRTI-naive and 27 NNRTI-experienced) with negative standard genotype for NNRTI resistance were tested using allele-specific PCR for mutants K103N and Y181C. 2010 The Journal of infectious diseases Result HIV K103N;Y181C 339;349 344;354 NNRTI;NNRTI;NNRTI;NNRTI;NNRTI 42;93;198;217;272 47;98;203;222;277 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Addition of the T477A substitution to the p51 RNH cleavage site mutants resulted in virions with elevated levels of p66 RT at RTV concentrations less than 0.1 muM and p66/p51 RT in the absence of RTV, suggesting relatively normal processing and proteolytic stability of RT. 2010 Retrovirology Result HIV T477A 16 21 RT;RT;RT 120;175;270 122;177;272 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. and the presence of T477A did not alter virion incorporation of Pr160gag-pol possessing inactive PR (data not shown). 2010 Retrovirology Result HIV T477A 20 25 Pol;PR;PR 73;64;97 76;66;99 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Effect of the RT T477A substitution on infectivity and virion RT content of p51 RNH cleavage site mutants. 2010 Retrovirology Result HIV T477A 17 22 RT;RT 14;62 16;64 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Effect of the RT T477A substitution on intravirion processing of the Pr160Gag-Pol polyprotein. 2010 Retrovirology Result HIV T477A 17 22 Pol;PR;RT 78;69;14 81;71;16 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. However, introduction of this substitution into a molecular clone of the F440V p51 RNH cleavage site mutant HIV-1 resulted in a significant increase in infectivity of this mutant virus. 2010 Retrovirology Result HIV F440V 73 78 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In order to validate the role of T477A in the reversion phenotype of F440V, we introduced this amino acid substitution into HIV-1 clones containing a variety of other p51 RNH cleavage site mutations that we previously showed to be detrimental to proper RT processing, as well as into wild-type HIV-1. 2010 Retrovirology Result HIV F440V;T477A 69;33 74;38 RT 253 255 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Interestingly, the T477A substitution also significantly improved the infectivity. 2010 Retrovirology Result HIV T477A 19 24 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Introduction of the T477A mutation into a wild-type HIV-1 background had no effect on virus replication. 2010 Retrovirology Result HIV T477A 20 25 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Table 1) and replication kinetics of 3 out of 6 other p51 RNH cleavage site mutants (data not shown) that originally showed severe attenuations in infectivity, despite the fact that this compensatory substitution arose only during passage of the F440V mutant. 2010 Retrovirology Result HIV F440V 246 251 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Table 1) as well as a considerable acceleration in viral spread (data not shown), thereby validating the compensatory nature of the T477A substitution in the context of the F440V p51 RNH cleavage site mutation. 2010 Retrovirology Result HIV F440V;T477A 173;132 178;137 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The impact of the T477A substitution was not due to increased virion incorporation of Pr160gag-pol, as normal levels of PR were present in all mutant viruses. 2010 Retrovirology Result HIV T477A 18 23 Pol;PR;PR 95;86;120 98;88;122 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The p51 RNH cleavage site mutants that showed improved infectivity due to the presence of the T477A substitution also showed significantly increased virion levels of RT. 2010 Retrovirology Result HIV T477A 94 99 RT 166 168 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. These virions produced in the presence of RTV concentrations above 0.1 muM showed higher molecular weight Gag-Pol polyprotein intermediate profiles similar to those seen in virions lacking the T477A substitution, due to RTV inhibition of normal viral polyprotein processing. 2010 Retrovirology Result HIV T477A 193 198 GagPol 106 113 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. To better evaluate the effect of p51 RNH cleavage site mutations in the absence and in the presence of the T477A substitution on the formation of mature RT p66/p51 heterodimers, we compared the intravirion accumulation of Pr160Gag-Pol polyprotein proteolytic processing intermediates by preparing virions in the presence of increasing concentrations of the HIV-1 PR inhibitor ritonavir (RTV). 2010 Retrovirology Result HIV T477A 107 112 Pol;PR;PR;RT 231;222;363;153 234;224;365;155 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Wild-type virions with or without the T477A substitution showed similar RTV dose-dependent diminutions in Pr55Gag and Pr160Gag-Pol proteolytic processing as assessed by decreasing levels of RT p66/p51 and Gag p24, and increasing levels of higher molecular weight polyproteins reactive with either RT-specific or Gag-p24-specific antibodies. 2010 Retrovirology Result HIV T477A 38 43 Pol;p24;p24;Gag;Gag;PR;PR;RT;RT 127;209;316;205;312;106;118;190;297 130;212;319;208;315;108;120;192;299 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. After a median antepartum zidovudine duration of 10.4 weeks in both groups and an additional 4 weeks postpartum zidovudine-plus-didanosine in PHPT-4, new NRTI resistance mutations were detected by consensus sequencing in five PHPT-4 subjects (2.3%; four K70R and one D67N+K70R) and two PHPT-2 controls (0.9%; one D67N, one K70R) (Table 4). 2010 Clinical infectious diseases Result HIV D67N;D67N;K70R;K70R;K70R 267;313;254;272;323 271;317;258;276;327 NRTI 154 158 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. Five PHPT-4 subjects and eight PHPT-2 controls had minor NNRTI mutations in postpartum samples (V179D, K101E, V106I, or V90I). 2010 Clinical infectious diseases Result HIV K101E;V106I;V179D;V90I 103;110;96;120 108;115;101;124 NNRTI 57 62 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. One PHPT-4 subject and two PHPT-2 controls already had NRTI resistance mutations detected at baseline (two T69N, one M41L). 2010 Clinical infectious diseases Result HIV M41L;T69N 117;107 121;111 NRTI 55 59 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. Using OLA, the K103N, G190A or Y181C mutations were detected postpartum in four (1.8%) PHPT-4 subjects versus 42 (18.9%) controls. 2010 Clinical infectious diseases Result HIV G190A;K103N;Y181C 22;15;31 27;20;36 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. a finding that is consistent with the notion that N348I in HIV-1 RT impacts the efficiency of the AZT-MP excision reaction by RNase H-dependent mechanism. 2010 AIDS (London, England) Result HIV N348I 50 55 RT 65 67 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Accordingly, N348I in HIV-1 RT compensates for the antagonism between TAMs and Y181C. 2010 AIDS (London, England) Result HIV N348I;Y181C 13;79 18;84 RT 28 30 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Accordingly, the assay window was not significantly large enough to reproducibly measure AZT resistance, antagonism of K70R by Y181C, and the subsequent recovery of the AZT resistance phenotype by introduction of the N348I mutation. 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C 119;217;127 123;222;132 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. As described previously, Y181C HIV-1 RT unblocked AZT-MP chain-terminated primers inefficiently on both DNA/DNA and RNA/DNA T/Ps (Fig.1B, 1C). 2010 AIDS (London, England) Result HIV Y181C 25 30 RT 37 39 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. As expected, N348I decreased the formation of the polymerase-independent RNase H cleavage product that reduced the RNA/DNA duplex to 10 nucleotides in length for both the K70R/M184V (Fig.5A) and K70R/L74V (Fig.5B) RTs. 2010 AIDS (London, England) Result HIV K70R;K70R;L74V;M184V;N348I 171;195;200;176;13 175;199;204;181;18 Pol;RT 50;214 60;217 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. As expected, Y181C also antagonized the ability of K70R RT to excise AZT-MP and recover DNA synthesis, although this defect was more pronounced on an RNA/DNA T/P than on a DNA/DNA T/P (Fig.1B, 1C). 2010 AIDS (London, England) Result HIV K70R;Y181C 51;13 55;18 RT 56 58 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. As reported previously, N348I significantly reduced the frequency of a polymerase-independent cleavage event that decreases the RNA/DNA duplex to 10 nucleotides. 2010 AIDS (London, England) Result HIV N348I 24 29 Pol 71 81 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Because the mechanism by which N348I in HIV-1 RT confers AZT resistance is different from that conferred by TAMs (described in Introduction), we hypothesized that Y181C might not antagonize the excision activity of N348I HIV-1 RT and, accordingly, that N348I may compensate for the Y181C-mediated antagonism of TAMs. 2010 AIDS (London, England) Result HIV N348I;N348I;N348I;Y181C;Y181C 31;215;253;163;282 36;220;258;168;287 RT;RT 46;227 48;229 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. By contrast, both the Y181C and K70R/Y181C enzymes were less efficient in generating full-length DNA product. 2010 AIDS (London, England) Result HIV K70R;Y181C;Y181C 32;22;37 36;27;42 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Consistent with previously published data, the introduction of either the L74V or the M184V mutations into HIV-1 RT containing K70R dramatically decreased the ATP-mediated AZT-MP excision activity of HIV-1 RT (Fig.4). 2010 AIDS (London, England) Result HIV K70R;L74V;M184V 127;74;86 131;78;91 RT;RT 113;206 115;208 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Furthermore, K70R in HIV-1 RT is associated with a strong ATP-mediated excision phenotype in vitro. 2010 AIDS (London, England) Result HIV K70R 13 17 RT 27 29 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. HIV-1 containing K70R did not confer significant resistance to AZT in these assays. 2010 AIDS (London, England) Result HIV K70R 17 21 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. However, in viruses that contained both K70R and T215Y (EC50 = 0.94 +- 0.13 microM, n = 5; 4.1-fold AZT resistance; p = 0.009), the introduction of the N348I mutation clearly compensated for the antagonism of the AZT-resistance phenotype by Y181C: the EC50 value for inhibition of replication of K70R/T215Y/Y181C/N348I HIV-1 by AZT (1.3 +- 0.5 microM, n = 4) was increased 2.8-fold relative to the K70R/T215Y/Y181C virus (EC50 = 0.46 +- 0.14 microM, n = 5; p = 0.032). 2010 AIDS (London, England) Result HIV K70R;K70R;N348I;T215Y;T215Y;Y181C;Y181C;K70R;N348I;T215Y;Y181C 296;398;313;301;403;307;409;40;152;49;241 300;402;318;306;408;312;414;44;157;54;246 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. However, the N348I mutation completely alleviated the antagonism of K70R by L74V (Fig.4B) and partially compensated for the antagonism of K70R by M184V (Fig.4A). 2010 AIDS (London, England) Result HIV K70R;K70R;L74V;M184V;N348I 68;138;76;146;13 72;142;80;151;18 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. In comparison with the WT enzyme, the K70R and Y181C mutations had minimal impact on the RNase H activity of RT. 2010 AIDS (London, England) Result HIV K70R;Y181C 38;47 42;52 RT 109 111 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. In the presence of 3 mM ATP, the N348I and K70R enzymes were significantly more efficient than WT enzyme in synthesizing full-length DNA product. 2010 AIDS (London, England) Result HIV K70R;N348I 43;33 47;38 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. In the RNase H activity experiments described above, we only assessed the activity of enzymes that contained both K70R and a mutation antagonistic to K70R. 2010 AIDS (London, England) Result HIV K70R;K70R 114;150 118;154 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. In this regard, the K70R mutation is one of the first TAMs to appear under AZT drug pressure. 2010 AIDS (London, England) Result HIV K70R 20 24 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Introduction of the N348I mutation into K70R/Y181C RT, however, significantly reduced the frequency of this polymerase-independent cleavage event. 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C 40;20;45 44;25;50 Pol;RT 108;51 118;53 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Introduction of the N348I mutation into RT containing K70R/Y181C RT increased the enzymes excision activity on the RNA/DNA T/P but not on the DNA/DNA T/P (Fig.1B, 1C). 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C 54;20;59 58;25;64 RT;RT 40;65 42;67 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. K70R) because we were interested to determine how N348I influenced the interplay between TAMs and Y181C at the onset of resistance development. 2010 AIDS (London, England) Result HIV N348I;Y181C;K70R 50;98;0 55;103;4 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Matthias Gotte and Vinay Pathak, have demonstrated that the N348I mutation in HIV-1 RT increases AZT resistance by decreasing the frequency of secondary RNase H cleavages that significantly reduce the RNA/DNA duplex length of the T/P and diminish the efficiency of AZT-MP excision. 2010 AIDS (London, England) Result HIV N348I 60 65 RT 84 86 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. N348I in HIV-1 RT also compensates for the antagonism of K70R by L74V and M181V. 2010 AIDS (London, England) Result HIV K70R;L74V;M181V;N348I 57;65;74;0 61;69;79;5 RT 15 17 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. N348I in HIV-1 RT compensates for the antagonism of K70R by Y181C. 2010 AIDS (London, England) Result HIV K70R;Y181C;N348I 52;60;0 56;65;5 RT 15 17 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Previous biochemical studies suggested that this phenotype was due to the Y181C mutation decreasing the AZT-MP excision activity of both WT and D67N/K70R/T215F/K219Q HIV-1 RT by directly impacting ATP binding and/or the rate of AZT-MP excision. 2010 AIDS (London, England) Result HIV D67N;K219Q;K70R;T215F;Y181C 144;160;149;154;74 148;165;153;159;79 RT 172 174 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Previous studies have demonstrated that the NRTI discrimination mutations L74V and M184V antagonize the AZT-MP excision phenotype of RT containing TAMs. 2010 AIDS (London, England) Result HIV L74V;M184V 74;83 78;88 NRTI;RT 44;133 48;135 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Taken together, these data show that the Y181C mutation does not antagonize the ability of N348I to excise AZT-MP via an RNase H-dependent mechanism in HIV-1 RT containing K70R. 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C 172;91;41 176;96;46 RT 158 160 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Taken together, these findings demonstrate that neither L74V nor M184V antagonizes the ability of N348I in HIV-1 RT to excise AZT-MP via an RNase H-dependent mechanism. 2010 AIDS (London, England) Result HIV L74V;M184V;N348I 56;65;98 60;70;103 RT 113 115 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. The EC50 value for inhibition of replication of K70R HIV-1 by AZT (0.27 +- 0.04 microM, n = 6) was increased only 1.2-fold relative to the WT virus (EC50 = 0.23 +- 0.04 microM, n = 6). 2010 AIDS (London, England) Result HIV K70R 48 52 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. the N348I mutation partially compensated for the antagonism between K70R and Y181C: more final DNA synthesis product was evident for the K70R/Y181C/N348I RT compared to the WT, Y181C and K70R/Y181C RTs. 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C;K70R;K70R;N348I;Y181C;Y181C;Y181C 137;148;142;68;187;4;77;177;192 141;153;147;72;191;9;82;182;197 RT;RT 154;198 156;201 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. The Y181C mutation in RT increases HIV-1 sensitivity to AZT even when multiple TAMs are co-selected on the same genome. 2010 AIDS (London, England) Result HIV Y181C 4 9 RT 22 24 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. Therefore, N348I in HIV-1 RT can also compensate for the antagonism of TAMs by L74V and M184V. 2010 AIDS (London, England) Result HIV L74V;M184V;N348I 79;88;11 83;93;16 RT 26 28 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. To determine whether L74V- or M184V-mediated antagonism of TAMs could also be rescued by the N348I mutation, we compared the AZT-MP excision and RNase H activities of K70R/L74V HIV-1 RT with K70R/L74V/N348I HIV-1 RT and K70R/M184V HIV-1 RT with K70R/M184V/N348I HIV-1 RT (Fig.4, Fig.5). 2010 AIDS (London, England) Result HIV K70R;K70R;L74V;M184V;N348I;N348I;K70R;K70R;L74V;L74V;M184V;M184V;N348I 191;245;196;250;201;256;167;220;21;172;30;225;93 195;249;200;255;206;261;171;224;25;176;35;230;98 RT;RT;RT;RT 183;213;237;268 185;215;239;270 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. To investigate this hypothesis, we examined the ability of recombinant HIV-1 RT containing combinations of Y181C, K70R and N348I to excise AZT-MP using established biochemical assay systems. 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C 114;123;107 118;128;112 RT 77 79 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. We also assessed the susceptibility of HIV-1 containing K70R, K70R/Y181C or K70R/Y181C/N348I to AZT in a TZM-bl indicator cell line. 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C;K70R;K70R;Y181C 76;87;81;56;62;67 80;92;86;60;66;72 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. We first examined the ability of WT, K70R, Y181C, K70R/Y181C, and K70R/Y181C/N348I HIV-1 RT to excise AZT-MP and rescue DNA synthesis from chain-terminated DNA/DNA and RNA/DNA T/Ps (Fig.1). 2010 AIDS (London, England) Result HIV K70R;N348I;Y181C;K70R;K70R;Y181C;Y181C 66;77;71;37;50;43;55 70;82;76;41;54;48;60 RT 89 91 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. we show that the observed in the formation of the polymerase-independent RNase H cleavage product that reduced the RNA/DNA duplex to 10 nucleotides by N348I RT relative to the WT RT is not significantly impacted by the introduction of the Y181C, L74V or M184V mutations. 2010 AIDS (London, England) Result HIV L74V;M184V;N348I;Y181C 246;254;151;239 250;259;156;244 Pol;RT;RT 50;157;179 60;159;181 20174661 HIV drug resistance surveillance using pooled pyrosequencing. Except for K20R which was detected by pyrosequencing only, 17 clinical, minor protease DR mutations were detected by both methods with extremely high concordance across a broad range of rates ( Figure 5 ). 2010 PloS one Result HIV K20R 11 15 PR 78 86 20174661 HIV drug resistance surveillance using pooled pyrosequencing. The L33I was detected in only two Sanger reads and correspondingly the majority of the pyrosequencing reads containing the same mutation cluster around those two sequences ( Figure 6b ). 2010 PloS one Result HIV L33I 4 8 20174661 HIV drug resistance surveillance using pooled pyrosequencing. The M46L and I84V mutations overwhelmingly clustered with the appropriate Sanger sequences that had the mixtures identified on the electropherograms ( Figure 3 ). 2010 PloS one Result HIV I84V;M46L 13;4 17;8 20174661 HIV drug resistance surveillance using pooled pyrosequencing. There are six clusters of pyrosequencing reads that cluster around the six L33V mutant sequences detected by Sanger sequencing ( Figure 6a ). 2010 PloS one Result HIV L33V 75 79 20174661 HIV drug resistance surveillance using pooled pyrosequencing. Two of these TDR mutations: M46L and I84V, detected at frequencies of 0.29% and 0.34% respectively, were also found in two Sanger sequences as mixed base calls ( Figure 2 ). 2010 PloS one Result HIV I84V;M46L 37;28 41;32 20227665 Flexible use of nuclear import pathways by HIV-1. As expected, infection by the N74D mutant was essentially unimpaired by mCPSF6-358 expression or TNPO3 depletion. 2010 Cell host & microbe Result HIV N74D 30 34 20227665 Flexible use of nuclear import pathways by HIV-1. As shown before, nondividing cells expressing mCPSF6-358 strongly restricted infection by wild-type HIV-1 but not N74D HIV-1. 2010 Cell host & microbe Result HIV N74D 114 118 20227665 Flexible use of nuclear import pathways by HIV-1. By contrast, CPSF6-358 co-purified more efficiently with wild-type versus N74D CA-NC cores (Figure 5D, left panel), at an average difference of 3.9-fold over four trials (data not shown). 2010 Cell host & microbe Result HIV N74D 74 78 NC;Capsid 82;79 84;81 20227665 Flexible use of nuclear import pathways by HIV-1. By contrast, infection by HIVNLdE CA N74D-luc/VSV-G was unaffected by the combination of cell-cycle arrest and mCPSF6-358 (Figure 4B). 2010 Cell host & microbe Result HIV N74D 37 41 Capsid 34 36 20227665 Flexible use of nuclear import pathways by HIV-1. By contrast, N74D HIV-1 infection was more strongly diminished in cells transfected with siRNAs for NUP85 or NUP155, and it was also impaired in cells transfected with siRNA to NUP160. 2010 Cell host & microbe Result HIV N74D 13 17 20227665 Flexible use of nuclear import pathways by HIV-1. Consistent with past reports, both E45A and Q63A/Q67A HIV-1 were impaired approximately 30-fold and 15-fold, respectively, in the infection of aphidicolin-treated control HeLa cells (Figure 6G). 2010 Cell host & microbe Result HIV E45A;Q63A;Q67A 35;44;49 39;48;53 20227665 Flexible use of nuclear import pathways by HIV-1. CPSF6-358-expressing cells were first infected with increasing amounts of wild-type and N74D HIV-1NLdE-luc. 2010 Cell host & microbe Result HIV N74D 88 92 20227665 Flexible use of nuclear import pathways by HIV-1. E45A HIV-1 infection was reduced 275-fold relative to dividing cells expressing mCPSF6-358, and Q63A/Q67A HIV-1 infection was decreased nearly 230-fold compared to cycling counterparts (Figure 6G). 2010 Cell host & microbe Result HIV Q63A;Q67A;E45A 96;101;0 100;105;4 20227665 Flexible use of nuclear import pathways by HIV-1. E45A or Q63A/Q67A mutation of CA impairs HIV-1 infection of cell-cycle arrested cells. 2010 Cell host & microbe Result HIV Q63A;Q67A;E45A 8;13;0 12;17;4 Capsid 30 32 20227665 Flexible use of nuclear import pathways by HIV-1. Even infection with HIVIN/D116N-HSA/VSV-G, which is deficient in integration and thus produces higher levels of 2-LTR circular vDNA, made far fewer circles in cells expressing mCPSF6-358 (Figure 3B). 2010 Cell host & microbe Result HIV D116N 26 31 LTR 114 117 20227665 Flexible use of nuclear import pathways by HIV-1. Having demonstrated that the N74D mutation allowed HIV-1 to escape the mCPSF6-358 block to nuclear entry, we asked whether any of the recently described host factors implicated in the nuclear transport of HIV-1 PICs were CA-dependent. 2010 Cell host & microbe Result HIV N74D 29 33 Capsid 221 223 20227665 Flexible use of nuclear import pathways by HIV-1. In comparison, CPSF6-300 purified with wild-type and N74D CA-NC complexes at an equal efficiency (Figure 5D, middle panel) in this and other experiments. 2010 Cell host & microbe Result HIV N74D 53 57 NC;Capsid 61;58 63;60 20227665 Flexible use of nuclear import pathways by HIV-1. In marked contrast to N74D HIV-1, mCPSF6-358 expression in the growth arrested HeLa cells strongly restricted infection by either E45A or Q63A/Q67A HIV-1. 2010 Cell host & microbe Result HIV E45A;N74D;Q63A;Q67A 130;22;138;143 134;26;142;147 20227665 Flexible use of nuclear import pathways by HIV-1. Indeed E45A or Q63A/Q67A HIV-1 was not restricted in dividing cells expressing mCPSF6-358 (Figure 6G). 2010 Cell host & microbe Result HIV E45A;Q63A;Q67A 7;15;20 11;19;24 20227665 Flexible use of nuclear import pathways by HIV-1. Infection with N74D HIV-1 was relatively unaffected by TNPO3 or RANBP2 depletion. 2010 Cell host & microbe Result HIV N74D 15 19 20227665 Flexible use of nuclear import pathways by HIV-1. Interestingly, N74D CA-NC complexes more efficiently precipitated rhTRIM5alpha (about two-fold) than wild-type CA-NC complexes in four separate trials (data not shown). 2010 Cell host & microbe Result HIV N74D 15 19 NC;NC;Capsid;Capsid 23;114;20;111 25;116;22;113 20227665 Flexible use of nuclear import pathways by HIV-1. Like N74D HIV-1, depletion of NUP155 or NUP160 impaired FIV infection whereas depletion of NUP153 was tolerated (Figure 6D, right panel). 2010 Cell host & microbe Result HIV N74D 5 9 HIV-FIV coinfections 56 69 20227665 Flexible use of nuclear import pathways by HIV-1. N74D HIV-1 infection was again decreased in cells depleted of NUP155 and NUP160. 2010 Cell host & microbe Result HIV N74D 0 4 20227665 Flexible use of nuclear import pathways by HIV-1. Not only were they TNPO3-independent, E45A and Q63A/Q67A HIV-1 were less affected by siRNA targeting of NUP155 than N74D HIV-1. 2010 Cell host & microbe Result HIV E45A;N74D;Q63A;Q67A 38;116;47;52 42;120;51;56 20227665 Flexible use of nuclear import pathways by HIV-1. Pre-infection with N74D HIV-1NL4dE-luc did not saturate the CPSF6-358 block to wild-type HIV-1. 2010 Cell host & microbe Result HIV N74D 19 23 20227665 Flexible use of nuclear import pathways by HIV-1. Sequence analysis of vDNA isolated from cells freshly infected with the resistant stock revealed a AAT -> GAT mutation in codon 74 of CA, causing an N74D change in the protein. 2010 Cell host & microbe Result HIV N74D 149 153 Capsid 134 136 20227665 Flexible use of nuclear import pathways by HIV-1. Similar to N74D HIV-1, FIV was unimpaired in the infection of cells depleted of TNPO3 (Figure 6D, middle panel). 2010 Cell host & microbe Result HIV N74D 11 15 20227665 Flexible use of nuclear import pathways by HIV-1. Similar to the uncloned resistant isolate, HIV-1NL4-3 CA N74D/BaL was neither impaired for infection or replication in HUT-R5.mCPSF6-358 cells (not shown). 2010 Cell host & microbe Result HIV N74D 57 61 Capsid 54 56 20227665 Flexible use of nuclear import pathways by HIV-1. Supporting such a model, challenge of 293T cells expressing human CPSF6-358 with increasing amounts of virus resulted in saturation of the block such that wild-type HIV-1 infected the restrictive cells as well as it did control cells, or as well as N74D HIV-1 infected CPSF6-358-expressing cells (Figure 5A). 2010 Cell host & microbe Result HIV N74D 249 253 HIV infections;HIV infections 165;254 179;268 20227665 Flexible use of nuclear import pathways by HIV-1. The ability of the N74D mutant to evade mCPSF6-358 restriction suggested that the antiviral protein might directly target wild-type CA protein. 2010 Cell host & microbe Result HIV N74D 19 23 Capsid 132 134 20227665 Flexible use of nuclear import pathways by HIV-1. The course of reverse transcription was measured using quantitative PCR (qPCR) in 293T cells expressing wild-type mCPSF6 or mCPSF6-358 after infection with wild-type HIV-HSA/VSV-G or HIVIN/D116N-HSA/VSV-G, the latter vector encoding IN with an inactivating mutation (Figure 3B). 2010 Cell host & microbe Result HIV D116N 189 194 RT;IN 14;233 35;235 20227665 Flexible use of nuclear import pathways by HIV-1. The infection profiles of E45A and Q63A/Q67A HIV-1 were distinct. 2010 Cell host & microbe Result HIV E45A;Q63A;Q67A 26;35;40 30;39;44 20227665 Flexible use of nuclear import pathways by HIV-1. The observation that infection with the N74D mutant was independent of TNPO3 suggested that this virus was transported to the nuclear pore by a pathway different from wild-type HIV-1, and thus might interact with different pore components. 2010 Cell host & microbe Result HIV N74D 40 44 20227665 Flexible use of nuclear import pathways by HIV-1. The single-cycle vector carrying the N74D mutation (HIVNLdE CA N74D-luc/VSV-G) also infected cells expressing an empty vector or mCPSF6-358 equally well; whereas the wild-type virus was restricted about 10-fold by mCPSF6-358 (Figure 4B). 2010 Cell host & microbe Result HIV N74D;N74D 37;63 41;67 Capsid 60 62 20227665 Flexible use of nuclear import pathways by HIV-1. These data collectively implied a reduced dependence of E45A and Q63A/Q67A HIV-1 on the nuclear pore for infection, or, stated differently, an inefficient interaction by these HIV-1 mutants with the nuclear pore complex. 2010 Cell host & microbe Result HIV E45A;Q63A;Q67A 56;65;70 60;69;74 20227665 Flexible use of nuclear import pathways by HIV-1. These data demonstrated that the N74D CA mutation was necessary and sufficient for HIV-1 resistance to mCPSF6-358. 2010 Cell host & microbe Result HIV N74D 33 37 Capsid 38 40 20227665 Flexible use of nuclear import pathways by HIV-1. TNPO3-independence by E45A and Q63A/Q67A HIV-1 prompted further examination of their NUP requirements in siRNA-treated cells. 2010 Cell host & microbe Result HIV E45A;Q63A;Q67A 22;31;36 26;35;40 20227665 Flexible use of nuclear import pathways by HIV-1. To assay for binding of CPSF6-358 to CA, we prepared wild-type and N74D CA-NC complexes in vitro. 2010 Cell host & microbe Result HIV N74D 67 71 NC;Capsid;Capsid 75;37;72 77;39;74 20227665 Flexible use of nuclear import pathways by HIV-1. Together, these data indicate that the karyopherin and nuclear pore requirements for wild-type and N74D HIV-1 vary due to a single residue change in CA, and karyopherin use by HIV-1 may be cell-cycle independent. 2010 Cell host & microbe Result HIV N74D 99 103 Capsid 149 151 20227665 Flexible use of nuclear import pathways by HIV-1. Transient expression of CPSF6-300 in 293T cells did not impair wild-type HIV-1 infection; by contrast, transient transfection of constructs expressing CPSF6-358 and even a full-length splice variant, CPSF6(72), restricted wild-type but not N74D HIV-1 (Figure 5C). 2010 Cell host & microbe Result HIV N74D 240 244 20227665 Flexible use of nuclear import pathways by HIV-1. Under these experimental conditions (see Supplemental Text for Figure 6), NUP153 depletion of HeLa cells also modestly impaired N74D HIV-1 infection. 2010 Cell host & microbe Result HIV N74D 128 132 20227665 Flexible use of nuclear import pathways by HIV-1. Unlike wild-type HIV-1, E45A or Q63A/Q67A HIV-1 infection was unaffected by reduced levels of TNPO3 in stable knockdown cells (Figure 6E). 2010 Cell host & microbe Result HIV E45A;Q63A;Q67A 24;32;37 28;36;41 20227665 Flexible use of nuclear import pathways by HIV-1. We next tested cells transiently depleted of NUP153, NUP155, and NUP160, factors whose depletion more significantly affected either wild-type or N74D HIV-1 infection. 2010 Cell host & microbe Result HIV N74D 145 149 HIV infections 150 165 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. A physical explanation may involve the fact that as a result of the shape of the 6-12 Lennard-Jones potential, Coulombic attractions (I37K, Q40K) lead to greater losses in DeltaDeltaEvdw than Coulombic repulsions (V38E). 2010 Biochemistry Result HIV I37K;Q40K;V38E 134;140;214 138;144;218 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Although L33S and L33Q are neutral there are significant changes both in size and polarity. 2010 Biochemistry Result HIV L33Q;L33S 18;9 22;13 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Although the correlation is high, the magnitudes of the computed FR values are, with the exception of L33S, systematically overpredicted by ca. 2010 Biochemistry Result HIV L33S 102 106 Capsid 140 142 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Although V38E share peaks with I37K and Q40K within the L33-L45 region (Figure 11a S35, V38, N42, and L45 positions) the magnitude of unfavorable changes at these sites is smaller. 2010 Biochemistry Result HIV I37K;Q40K;V38E 31;40;9 35;44;13 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. An additional MD simulation was run for I37K which employed a different random seed number in an attempt to yield a trajectory with improved equilibrium/convergence statistics. 2010 Biochemistry Result HIV I37K 40 44 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. As all mutations except L33S result in a larger sidechain the offset could be related to size and associated entropic terms not included in the calculations. 2010 Biochemistry Result HIV L33S 24 28 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. As L33S and L33Q are both polar mutations similarities in DeltaDeltaEcoul profiles are not unexpected. 2010 Biochemistry Result HIV L33Q;L33S 12;3 16;7 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. As shown in Figure 7 simulation convergence was additionally assessed by plotting autocorrelation functions (ACF) and block averaged standard errors of the mean (BASEM) for the DeltaGbind calcd time-series from T20 with wildtype gp41, as well as seven gp41 mutants (L33Q, L33S, G36V, I37K, V38E, Q40H, Q40K). 2010 Biochemistry Result HIV G36V;I37K;L33Q;L33S;Q40H;Q40K;V38E 278;284;266;272;296;302;290 282;288;270;276;300;306;294 gp41;gp41 229;252 233;256 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. BASEM curves for similarly reveal I37K as an outlier in terms of poorly converged error estimates. 2010 Biochemistry Result HIV I37K 34 38 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Champagne et al reported four T20 substitutions L152A, D153A, W155A, and A156Q each of which resulted in a loss of binding with wildtype gp41. 2010 Biochemistry Result HIV A156Q;D153A;L152A;W155A 73;55;48;62 78;60;53;67 gp41 137 141 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Comparison of DeltaDeltaEvdw for charged mutations reveals that the shapes of all three curves are generally similar with the exception that relative to V38E, mutations I37K and Q40K (Figure 11b green, blue, vs red lines) both show significant energetic losses in the contiguous region between residues L33 and L45 (Figure 11b). 2010 Biochemistry Result HIV I37K;Q40K;V38E 169;178;153 173;182;157 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Comparison of the key Coulombic changes for L33S and L33Q (Figure 11d orange vs yellow lines). 2010 Biochemistry Result HIV L33Q;L33S 53;44 57;48 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Favorable interactions here involving Leu residues are consistent with the authors' suggestion that clinically observed secondary S138A mutation (or other non-aromatic hydrophobic substitutions) compensates for losses resulting from the commonly observed N43D mutation through increased favorable packing with L44 and L45. 2010 Biochemistry Result HIV N43D;S138A 255;130 259;135 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. For position D153, although favorable packing is not significant (Figure 12 y-axis), the strong salt bridge with R31 noted earlier would be disrupted by D153A, and, as postulated by Champagne et al, affinity would likely be lost as a result of the mutation. 2010 Biochemistry Result HIV D153A 153 158 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. For V38E, intermolecular repulsions which occurs as a result of the change to a negative residue leads to large losses in favorable DeltaDeltaEcoul (Table 3 column C) and a corresponding unfavorable solvent-mediated electrostatic energy DeltaDeltaGelec (Table 3 column F). 2010 Biochemistry Result HIV V38E 4 8 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. For V38E, the differential footprint for van der Waals energy is much flatter (Figure 11a red line) which leads to small (1.06 kcal/mol) unfavorable changes (Table 3 column B) in steric packing compared with I37K (13.85 kcal/mol) or Q40K (20.18 kcal/mol). 2010 Biochemistry Result HIV I37K;Q40K;V38E 208;233;4 212;237;8 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Further, despite the opposite charge, V38E shows a FR change which minimally differs by only ca. 2010 Biochemistry Result HIV V38E 38 42 Capsid 93 95 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Given the relatively weak initial interaction observed between T128 and gp41 (Figure 12 y-axis blue ellipsoid), the experimentally observed increase in binding energy for T128I analog is likely a function of increased favorable packing with adjacent hydrophobic Leu residues in the gp41 range 54-57. 2010 Biochemistry Result HIV T128I 171 176 gp41;gp41 72;282 76;286 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Here, glutamine is more polar than serine which could explain the accentuated unfavorable DeltaDeltaEcoul effects of the L33Q mutation as compared to L33S at positions Q40, Q41, R46 (Figure 11d orange vs yellow lines). 2010 Biochemistry Result HIV L33Q;L33S 121;150 125;154 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Here, V38E introduces a negative charge on gp41 (3 red spheres), which is proximal to a total of seven Glu and Asp residues on T20, (Figure 10a red sticks) thus leading to repulsion between negatively charged sidechains (red line, Figure 10b). 2010 Biochemistry Result HIV V38E 6 10 gp41;Asp 43;111 47;114 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. However, additional losses for L33Q relative to L33S are observed in a cluster of four hydrophobic residues at locations A22, M24, T25, and L26, likely related to suboptimal packing of the more bulky glutamine side chain relative to serine. 2010 Biochemistry Result HIV L33Q;L33S 31;48 35;52 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. However, experimentally (see Table 1) the Q40K mutation is much more detrimental than I37K. 2010 Biochemistry Result HIV I37K;Q40K 86;42 90;46 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. I37K and Q40K mutations show the corresponding opposite effect (dark and light blue lines, Figure 10b) by which introduction of positively charged gp41 residues (Figure 10a blue spheres) leads to dramatic favorable energetic increases with nearby negative T20 residues (Figure 10a red sticks). 2010 Biochemistry Result HIV Q40K;I37K 9;0 13;4 gp41 147 151 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In contrast, prior experimental studies have suggested T20 C-terminal residues may not interact with gp41. 2010 Biochemistry Result HIV T20C 55 60 gp41 101 105 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In contrast, Q40H reveals no change in DeltaDeltaEvdw at position 40. 2010 Biochemistry Result HIV Q40H 13 17 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In contrast, the profile for V38E shows the opposite effect (Figure 11b red line). 2010 Biochemistry Result HIV V38E 29 33 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In general, Coulombic profiles for Q40H and G36V (Figure 11d magenta and purple lines) show fewer per-residue losses and are also somewhat flatter compared to L33S and L33Q (Figure 11d orange and yellow lines) which could play a role in these mutations being less detrimental. 2010 Biochemistry Result HIV G36V;L33Q;L33S;Q40H 44;168;159;35 48;172;163;39 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In particular, the two mutations yielding the largest losses (Table 3 column G, DeltaH-bond) are for Q40H and Q40K which is consistent with the Q40 being the strongest H-bonding residue in the peptide binding interface (see Figure 8). 2010 Biochemistry Result HIV Q40H;Q40K 101;110 105;114 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In support of this argument, differential changes in DeltaDeltaEvdw localized to the mutations sites show no loss in energy at I37K (Figure 11a green line) compared with Q40K (Figure 11a blue line). 2010 Biochemistry Result HIV I37K;Q40K 127;170 131;174 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Interestingly, differential footprints show significant energy loss for L33S at position 33 while L33Q shows only minimal change (Figure 11c orange vs yellow line). 2010 Biochemistry Result HIV L33Q;L33S 98;72 102;76 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Interestingly, the ACF results for T20 with I37K show a distinctly different trend (green solid arrow), in comparison to other trajectories, which is an indication this one simulation is not in reasonable equilibrium or as well-behaved. 2010 Biochemistry Result HIV I37K 44 48 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Likewise, gains at position 36 for van der Waals as a result of G36V (Figure 11c magenta line) are physically reasonable given the increase in size and hydrophobicity. 2010 Biochemistry Result HIV G36V 64 68 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Losses localized to position 33 are consistent with L33S leading to reduction in size for serine relative to either glutamine or leucine. 2010 Biochemistry Result HIV L33S 52 56 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Nevertheless, despite the L33S offset in comparison with the other results in Figure 9, use of the gp41 model to predict relative FR energies leads to good overall agreement with experiment. 2010 Biochemistry Result HIV L33S 26 30 gp41 99 103 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Notably, the calculations correctly predict that L33Q and Q40K have the largest loss of binding. 2010 Biochemistry Result HIV L33Q;Q40K 49;58 53;62 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Only the L33S-wildtype change does not lead to a loss in steric packing. 2010 Biochemistry Result HIV L33S 9 13 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Overall, the simulation results suggest that DeltaDeltaGFR is dominated by losses in favorable steric packing for I37K and Q40K vs losses in favorable electrostatic energy for V38E as a result of large changes in Coulombic attraction or repulsion. 2010 Biochemistry Result HIV I37K;Q40K;V38E 114;123;176 118;127;180 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Q40K and I37K are analogous in that both result in a replacement of a neutral residue with a positively charged residue and, due to the residue per turn ratio of the gp41 coiled-coil alpha helices, the mutations are in similar locations (see Figure 10a). 2010 Biochemistry Result HIV I37K;Q40K 9;0 13;4 gp41 166 170 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Stated another way, negatively charged T20 is pulled towards positive mutations on gp41 (I37K and Q40K) which affects DeltaDeltaEvdw more significantly (more unfavorable changes to DeltaDeltaEvdw) than repulsion as a result of the negatively charged mutation (V38E). 2010 Biochemistry Result HIV I37K;Q40K;V38E 89;98;260 94;102;264 gp41 83 87 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. T20 has an overall net formal charge of -5 and in the case of I37K and Q40K the resultant added positive charge leads to large Coulombic attraction directly at the site of the mutations (Figure 11b green and blue lines). 2010 Biochemistry Result HIV I37K;Q40K 62;71 66;75 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. The mutations L33S and L33Q both represent nonpolar to polar mutations occurring at the same location on gp41 and originating from the same wildtype residue. 2010 Biochemistry Result HIV L33Q;L33S 23;14 27;18 gp41 105 109 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. The net effect is positively charged mutations (Q40K, I37K) yield the most negative DeltaDeltaGelec values in contrast to the negatively charged mutation (V38E) which yields the most positive DeltaDeltaGelec value (Table 3 column F). 2010 Biochemistry Result HIV I37K;Q40K;V38E 54;48;155 58;52;159 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. The same study also reported that a T128I substitution on T20 resulted in an increase in binding. 2010 Biochemistry Result HIV T128I 36 41 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. The significant Coulombic attractions for I37K and Q40K seen in Figure 11b appear to be coupled to the large losses in favorable van der Waals energy seen in the DeltaDeltaEvdw footprints (Figure 11a). 2010 Biochemistry Result HIV I37K;Q40K 42;51 46;55 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. The simulations also correctly predict that changes in nonpolar energy are smallest for L33S which is the only mutation that results in a less bulky sidechain relative to wildtype (Table 3 column E, DeltaDeltaGnonpolar = 0.06 kcal/mol). 2010 Biochemistry Result HIV L33S 88 92 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Therefore, changes in binding as a result of mutations at L33 are due solely to differences in the final state in contrast to Q40K and I37K for which FR appears to be primarily a function of differences originating in the initial state. 2010 Biochemistry Result HIV I37K;Q40K 135;126 139;130 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. This latter case is probably related to the fact noted above that L33S is the only mutation which leads to a smaller sidechain. 2010 Biochemistry Result HIV L33S 66 70 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. To further validate the model seven additional MD simulations of the same length were performed to compute the energetic effects of L33Q, L33S, G36V, I37K, V38E, Q40H, and Q40K for comparison with experiment (Figure 9, Table 3). 2010 Biochemistry Result HIV G36V;I37K;L33Q;L33S;Q40H;Q40K;V38E 144;150;132;138;162;172;156 148;154;136;142;166;176;160 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. As shown in Figure 3, VLPs produced by H69Q mutant displayed a p24 pattern similar to the wild-type control; and both H69N and H69E showed partial Gag processing activities. 2010 Retrovirology Result HIV H69E;H69N;H69Q 127;118;39 131;122;43 p24;Gag 63;147 66;150 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Based on these observations, we suggested that cysteine 95 is the primary residue facilitating protease autoprocessing and the subsequent Gag processing; L63 and C67 can also rescue the H69E inhibitory effect to a less extent probably because of the fact that they are in the close proximity to H69 residue in primary sequence. 2010 Retrovirology Result HIV H69E 186 190 PR;Gag 95;138 103;141 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. C95 and other residues dampened the inhibitory effect of H69E on protease autoprocessing. 2010 Retrovirology Result HIV H69E 57 61 PR 65 73 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Charge substitutions of several residues did not rescue inhibition of H69E on protease maturation. 2010 Retrovirology Result HIV H69E 70 74 PR 78 86 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Consistent with our previous report, VLPs produced by wtpse H69E contained predominantly the full length Gag polyprotein and no processed p24, indicating lack of mature protease activity (Figure 2, lane 3). 2010 Retrovirology Result HIV H69E 60 64 PR;p24;Gag 169;138;105 177;141;108 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Consistent with the partial Gag processing activities, H69E and H69N VLPs contained reduced amounts of mature protease as well as partially processed intermediates. 2010 Retrovirology Result HIV H69E;H69N 55;64 59;68 PR;Gag 110;28 118;31 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Given that there are six point mutations between NL4-3 and wtpse protease, our data suggested that the inhibitory effect of H69E on protease autoprocessing is influenced by other residues. 2010 Retrovirology Result HIV H69E 124 128 PR;PR 65;132 73;140 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. H69D mutation abolishes protease autoprocessing even in the context of NL4-3 PR backbone. 2010 Retrovirology Result HIV H69D 0 4 PR;PR 24;77 32;79 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. H69E mutation displayed different effects under two different contexts. 2010 Retrovirology Result HIV H69E 0 4 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. H69E mutation significantly inhibits protease maturation (lane 3). 2010 Retrovirology Result HIV H69E 0 4 PR 37 45 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In addition to H69E mutation, a previous study using bacterially expressed Gag-Pol precursor demonstrated inhibition of protease autoprocessing by H69D; whereas changes to R, L, Y, N, and Q, individually, did not impair protease autoprocessing. 2010 Retrovirology Result HIV H69D;H69E 147;15 151;19 PR;PR;GagPol 120;220;75 128;228;82 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In contrast, H69D VLPs only contained the full length p55 precursor; no processed intermediates or p24 were detected (Figure 3 lane 4), which resembled the D25N negative control. 2010 Retrovirology Result HIV D25N;H69D 156;13 160;17 p24 99 102 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In contrast, wtpse H69E/A95C mutant, which contains single amino acid reversion at residue 95, showed a relative Gag processing activity close to NL4-3 H69E mutant, indicating that C95 could facilitate autoprocessing. 2010 Retrovirology Result HIV A95C;H69E 24;19 28;23 Gag 113 116 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In D25N, H69D, and wtpse H69E VLPs, minimal or no mature protease was detected; and the full length Gag-PR precursor appeared to be the predominant product. 2010 Retrovirology Result HIV D25N;H69D;H69E 3;9;25 7;13;29 PR;Gag;PR 57;100;104 65;103;106 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In order to define residues that rescued protease autoprocessing in the NL4-3 H69E construct, we engineered a panel of H69E proviruses replacing the six point mutations in the wtpse backbone with the corresponding NL4-3 amino acids individually or in combination (Figure 1B) and tested their Gag processing efficiencies to evaluate autoprocessing activities (Figure 2). 2010 Retrovirology Result HIV H69E 119 123 PR;Gag 41;292 49;295 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In our previous report, H69E and other mutations were constructed in the context of a pseudo wild type (wtpse) protease sequence, in which H69E significantly impedes precursor autoprocessing. 2010 Retrovirology Result HIV H69E;H69E 24;139 28;143 PR 111 119 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In the absence of any protease activity, as with D25N mutant, the full length Gag polyprotein (p55) is the predominant product in transfected cells and the released VLPs (Figure 2 lane 10). 2010 Retrovirology Result HIV D25N 49 53 PR;Gag 22;78 30;81 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. In VLPs produced from H69Q, mature protease was the primary form similar to the wild type control. 2010 Retrovirology Result HIV H69Q 22 26 PR 35 43 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Interestingly, the double mutation I63L/A67C also demonstrated rescued Gag processing to a less extent (Figure 2 lane 6). 2010 Retrovirology Result HIV A67C;I63L 40;35 44;39 Gag 71 74 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. It is interesting that H69D mutation displays a more drastic inhibitory effect than H69E considering the carboxyl side chain of aspartic acid is only shorter by one methyl group (-CH2) than that of glutamic acid. 2010 Retrovirology Result HIV H69D;H69E 23;84 27;88 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Mutations Q7K, L33I, and L63I are known to minimize autoproteolysis; and C67A/C95A mutations prevent aggregation of E. 2010 Retrovirology Result HIV C67A;C95A;L33I;L63I;Q7K 73;78;15;25;10 77;82;19;29;13 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. One speculation is that positively charged side chains of the parental residues (H69 or K69) interact with another negatively charged residue to facilitate proper folding; and the carbonyl group of H69E disrupts the electrostatic interaction. 2010 Retrovirology Result HIV H69E 198 202 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Our previous study also suggested that H69E mutation inhibits in vitro autoprocessing probably by affecting proper precursor folding. 2010 Retrovirology Result HIV H69E 39 43 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Out of a total of 12 constructs (E21K, E21Q, D31K, D31N, E34K, E35K, E34K/E35K, F99K, F99N, F99Q, F99H, F99A), none of them reversed the inhibitory effect of H69E on protease maturation (not all the mutants are shown here) and many of them further suppressed autoprocess activity (Figure 4, lanes 4-9). 2010 Retrovirology Result HIV D31K;D31N;E21K;E21Q;E34K;E34K;E35K;E35K;F99A;F99H;F99K;F99N;F99Q;H69E 45;51;33;39;57;69;63;74;104;98;80;86;92;158 49;55;37;43;61;73;67;78;108;102;84;90;96;162 PR 166 174 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Quantitative analysis demonstrated relative Gag processing efficiencies following an order of wt H69Q > H69N, H69E >> H69D in VLPs produced from transfected mammalian cells (Figure 3B). 2010 Retrovirology Result HIV H69D;H69E;H69N;H69Q 120;112;106;99 124;116;110;103 Gag 44 47 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. The wtpse H69E mutants carrying NL4-3 Q7, L33/N37 demonstrated a phenotype very similar to the wtpse H69E, suggesting that these residues contributed minimally to the rescue effect. 2010 Retrovirology Result HIV H69E;H69E 10;101 14;105 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. To compare H69E with H69D for their effects on protease maturation under the same context, we engineered a panel of mutations changing the parental H69 to D, N and Q individually in the pNL-PR backbone. 2010 Retrovirology Result HIV H69D;H69E 21;11 25;15 PR;PR 47;190 55;192 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. To further understand the inhibition mechanism of H69E on protease autoprocessing, we first sought to examine the effects of H69E in the context of NL4-3 protease. 2010 Retrovirology Result HIV H69E;H69E 50;125 54;129 PR;PR 58;154 66;162 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. We chose to mutate five surface residues (four acidic acids plus F99 that is in close proximity to H69) individually in the H69E context to examine whether a neutral or positively charged residue at these positions could rescue protease autoprocessing by complementing mutations. 2010 Retrovirology Result HIV H69E 124 128 PR 228 236 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. We quantified the ratio of p24 to total p24-containing proteins as a measure of relative Gag processing efficiency to indirectly reflect autoprocessing activity, and our data demonstrated that wtpse H69E mutation had <5% of the wild type processing activity. 2010 Retrovirology Result HIV H69E 199 203 p24;p24;Gag 27;40;89 30;43;92 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Altogether, uncoupled chromatin- and LEDGF-binding affinities were observed for IN mutants H171A, L172A and EK170,1AA, with strong binding affinity to chromatin but dramatically impaired contact with LEDGF/p75. 2010 Virology journal Result HIV H171A;L172A 91;98 96;103 IN 80 82 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Besides the previously reported IN mutants, V165A, A179P, KR186,7AA and a class I mutant D64/D116AA, several new YFP-IN mutants were generated by site-directed mutagenesis. 2010 Virology journal Result HIV D116A;A179P;V165A 93;51;44 98;56;49 IN;IN 32;117 34;119 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. By contrast, mutants K136A, H171A, L172A, I182A and I203A were still able to associate with chromatin. 2010 Virology journal Result HIV H171A;I182A;I203A;K136A;L172A 28;42;52;21;35 33;47;57;26;40 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. In parallel, the 293T cells transfected with the YFP-IN V165A mutant, which has been shown to be defective of chromatin binding, was used as a negative control. 2010 Virology journal Result HIV V165A 56 61 IN 53 55 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Indeed, this region overlaps with the interface for LEDGF-binding in the crystal study, and some IN mutants within this region, such as E170A, H171A, and LK172,3AA, have been shown to be impaired in the ability to bind LEDGF/p75. 2010 Virology journal Result HIV E170A;H171A 136;143 141;148 IN 97 99 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Interestingly, several IN mutants including V165A, L172A, V176A, A179P, KR186,7AA, I203P lost their interaction with LEDGF. 2010 Virology journal Result HIV A179P;I203P;L172A;V165A;V176A 65;83;51;44;58 70;88;56;49;63 IN 23 25 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Interestingly, two IN mutants, H171A and L172A, that showed differential binding abilities to chromatin and to LEDGF/p75 are located in the CCD loop region 170EHLK173 of IN, a connector that links helices alpha4 and alpha5. 2010 Virology journal Result HIV H171A;L172A 31;41 36;46 IN;IN 19;170 21;172 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Interestingly, we noted that IN mutants, H171A and L172A, displayed a drastically reduced interaction with LEDGF/p75 but still retained the interaction with chromatin. 2010 Virology journal Result HIV H171A;L172A 41;51 46;56 IN 29 31 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Meanwhile, the mutagenic studies have highlighted the importance of E170A, H171A, LK172,3AA for LEDGF/p75 interaction. 2010 Virology journal Result HIV E170A;H171A 68;75 73;80 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Meanwhile, the mutants K159P, H171A, and I200A showed reduced affinity for LEDGF/p75. 2010 Virology journal Result HIV H171A;I200A;K159P 30;41;23 35;46;28 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Our data showed that, in addition to the previously described IN mutants (V165A, A179P, KR186,7AA) K159P, V176A, A179I, I203P were also severely impaired for host chromatin binding. 2010 Virology journal Result HIV A179I;A179P;I203P;K159P;V165A;V176A 113;81;120;97;74;106 118;86;125;104;79;111 IN 62 64 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Our previous study showed that three IN CCD mutants V165A, A179P, KR186,7AA, which cannot bind LEDGF/p75, lack the ability to bind to host chromatin. 2010 Virology journal Result HIV A179P;V165A 59;52 64;57 IN 37 39 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Results revealed a strong interaction between T7-LEDGF and YFP-IN wild type and mutants D64E/D116A, K136A, I182A, F185A, I203A. 2010 Virology journal Result HIV D116A;D64E;F185A;I182A;I203A;K136A 93;88;114;107;121;100 98;92;119;112;126;105 IN 63 65 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. The chromatin binding affinity of F185A and I200A was reduced by approximately 60% of wild type IN. 2010 Virology journal Result HIV F185A;I200A 34;44 39;49 IN 96 98 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. All infant envelopes had a W680G substitution and were highly resistant to mAb 4E10 (IC50>100 microg/mL). 2010 PloS one Result HIV W680G 27 32 Env 11 20 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Both W680 and W680R clones were sensitive to 4E10 (IC50 3.3 microg/mL and 6.6 microg/mL, respectively). 2010 PloS one Result HIV W680R 14 19 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. By this time, the distribution of MPER substitutions had changed; only 1 clone out of 15 had a W680G substitution (IC50>50 microg/mL), while the remaining Envs had either a W (9/15 clones) or an R (5/15 clones) at position 680. 2010 PloS one Result HIV W680G 95 100 Env 155 159 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Examination of the entire MPER did not reveal any additional mutations associated with 4E10 sensitivity in the W680R Envs. 2010 PloS one Result HIV W680R 111 116 Env 117 121 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. One maternal clone had a W672R substitution in addition to a W680G mutation and was highly resistant to 4E10 (IC50>100 microg/mL) 2010 PloS one Result HIV W672R;W680G 25;61 30;66 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. One maternal clone had a W672R substitution in addition to a W680G mutation and was highly resistant to 4E10 (IC50>100 microg/mL). 2010 PloS one Result HIV W672R;W680G 25;61 30;66 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Previously published in vitro mutagenesis data showed that a W680A substitution resulted in a marginal increase in 4E10 resistance at the IC50 level, but greatly increased resistance at the IC90 . 2010 PloS one Result HIV W680A 61 66 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Since our W680G Envs also contain a small, hydrophobic substitution at this position, we tested the Envs from subject 16M for T20 susceptibility. 2010 PloS one Result HIV W680G 10 15 Env;Env 16;100 20;104 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Some of the previously described F673L Envs also had substitutions in the lentiviral lytic peptide - 2 (LLP-2) domain of the gp41 cytoplasmic tail. 2010 PloS one Result HIV F673L 33 38 gp41;Env 125;39 129;43 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The 4E10-resistant clone had the F673L substitution previously described by Gray et al. 2010 PloS one Result HIV F673L 33 38 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The majority of the Env clones (36/47) detected in Subject 16M possessed a glycine at position 680 instead of the usual tryptophan (W680G) and all tested clones were resistant to mAb 4E10 (IC50>100 microg/mL). 2010 PloS one Result HIV W680G 132 137 Env 20 23 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The majority of the maternal envs (12/14) in this subject had a W680R substitution, with a minor fraction (2/14) possessing the wild-type W680. 2010 PloS one Result HIV W680R 64 69 Env 29 33 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The remaining clones had either a wild-type W (2/47) or a W680R (9/47) substitution at this position (Figure 2A). 2010 PloS one Result HIV W680R 58 63 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The variations in 4E10 susceptibility in subject 12M's Env containing W680R are consistent with a model in which residues outside the MPER are critical for high-level resistance mediated by position 680. 2010 PloS one Result HIV W680R 70 75 Env 55 58 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The W680 Envs from this subject also had a very rare I684L substitution in the membrane-spanning domain (present in both maternal and infant W680 Envs). 2010 PloS one Result HIV I684L 53 58 Env;Env 9;146 13;150 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The W680G Envs from this subject were ~2-fold more susceptible to T20 than Envs with either a W or R at position 680. 2010 PloS one Result HIV W680G 4 9 Env;Env 10;75 14;79 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The W680G mutation was associated with a K at position 677, a Q at position 683, and an I at position 686. 2010 PloS one Result HIV W680G 4 9 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The W680R Envs had a wide range of susceptibility to 4E10 (IC50 11 to >50 microg/mL), suggesting that position 680 was not the sole determinant of 4E10 sensitivity for this subject. 2010 PloS one Result HIV W680R 4 9 Env 10 14 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The W680R mutation was associated with a charged residue at position 677 (K) and an uncharged residue at position 683 (Q). 2010 PloS one Result HIV W680R 4 9 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. The W680R mutation was associated with an N at position 677, a Q at position 683, and an L at position 686. 2010 PloS one Result HIV W680R 4 9 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. These substitutions (E783A, T784I, G789V, T792L) were not present in any of the envs from our subject. 2010 PloS one Result HIV E783A;G789V;T784I;T792L 21;35;28;42 26;40;33;47 Env 80 84 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. To confirm that the W680G substitution in subject-pair 16 was essential for conferring the 4E10-resistant phenotype, we conducted site-directed mutagenesis to revert an infant envelope to the wild type (G680W). 2010 PloS one Result HIV G680W;W680G 203;20 208;25 Env 176 184 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. At least one of the three resistance mutations was detected at NVP-ART initiation in 26% of the 148 women exposed to sdNVP with OLA results: 13% with the K103N mutation, 5% with the Y181C, and 19% with the G190A. 2010 Clinical infectious diseases Result HIV G190A;K103N;Y181C 206;154;182 211;159;187 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. The OLA was indeterminate for all three codons in one woman, excluded from analysis (Figure 1), and for a single codon in four other women (one at position 103, one 181, and two 190 including one with an identified K103N mutation). 2010 Clinical infectious diseases Result HIV K103N 215 220 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. Virologic failure was also increased (Table 2) with the detection by OLA of each of the three mutations (K103N and Y181C: P<.0001; G190A: P=.001); a viral load above the median at enrollment during pregnancy (4.58 log10 copies/mL) or at initiation of NVP-ART (4.77 log10 copies/mL) (P=.004 and .01, respectively); a CD4 cell count below the median (183 cells/uL) during pregnancy (P=.02) but not at initiation of NVP-ART (median 153 cells/uL, P=.61); and with an interval of less than 6 months between delivery and NVP-ART initiation (P<.0001). 2010 Clinical infectious diseases Result HIV G190A;K103N;Y181C 131;105;115 136;111;120 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. 2A and B), consistent with the hypothesis that the property of EFV-dependent growth stimulation contributes to the improved fitness of K101E+G190S relative to G190S in 400 and 600 nM EFV. 2010 Virology Result HIV G190S;G190S;K101E 141;159;135 146;164;140 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. 6A) and (M41L+T215Y) improved replication fitness in the absence of EFV. 2010 Virology Result HIV M41L;T215Y 9;14 13;19 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Because p24 concentrations of independent cultures may not be directly comparable, we used growth competition assays to confirm that NL4-3 virus with the D10 RT sequence was more fit than G190S in the presence of EFV concentrations associated with drug-dependent stimulation of replication. 2010 Virology Result HIV G190S 188 193 p24;RT 8;158 11;160 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. but still remained substantially less fit than G190S in an NL4-3 backbone. 2010 Virology Result HIV G190S 47 52 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Drug susceptibility assays indicated that the L74V mutation abolished the EFV-dependent growth stimulation of (K101E+G190S), without reducing its degree of EFV resistance. 2010 Virology Result HIV G190S;K101E;L74V 117;111;46 122;116;50 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Effects of the nucleoside resistance mutation L74V on the replication fitness, EFV resistance, and EFV-dependent stimulation of (K101E+G190S) 2010 Virology Result HIV G190S;K101E;L74V 135;129;46 140;134;50 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Effects of the nucleoside resistance mutation L74V on the replication fitness, EFV resistance, and EFV-dependent stimulation of (K101E+G190S). 2010 Virology Result HIV G190S;K101E;L74V 135;129;46 140;134;50 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Effects of the nucleoside resistance mutations M41L+T215Y on the replication fitness, EFV resistance, and EFV-dependent stimulation of K101E+G190S. 2010 Virology Result HIV G190S;K101E;M41L;T215Y 141;135;47;52 146;140;51;57 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. However, the ([M41L+T215Y] + [K101E+G190S]) quadruple mutant in an NL4-3 RT backbone became less fit compared to K101E+G190S at higher concentrations of EFV (PRR=0.85+-0.03 at 400 nM EFV), suggesting that (M41L+T215Y) reduces the EFV-dependent stimulation and/or EFV resistance of (K101E+G190S). 2010 Virology Result HIV G190S;G190S;G190S;K101E;K101E;K101E;M41L;M41L;T215Y;T215Y 36;119;288;30;113;282;15;206;20;211 41;124;293;35;118;287;19;210;25;216 RT 73 75 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. However, the presence of (M41L+T215Y) in the D10 background did not fully suppress EFV-dependent growth stimulation of (K101E+G190S). 2010 Virology Result HIV G190S;K101E;M41L;T215Y 126;120;26;31 131;125;30;36 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Identification of a clinical RT sequence containing K101E+G190S that has improved fitness compared to K101E+G190S in an NL4-3 backbone. 2010 Virology Result HIV G190S;G190S;K101E;K101E 58;108;52;102 63;113;57;107 RT 29 31 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. In addition, polymorphism(s) in D10 limit the suppressive effect of (M41L+T215Y) on the EFV-dependent growth stimulation conferred by (K101E+G190S). 2010 Virology Result HIV G190S;K101E;M41L;T215Y 141;135;69;74 146;140;73;79 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. In order to better understand how K101E augments the relative fitness of G190S in the presence of EFV, we performed drug resistance assays, in which PM1 cells were infected separately by each mutant, and supernatant p24 antigen concentration was measured after six days of growth in different concentrations of EFV. 2010 Virology Result HIV G190S;K101E 73;34 78;39 p24 216 219 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. In order to determine the impact of RT backbone sequences on the properties of the K101E+G190S double mutant, we constructed a pNL4-3 clone containing an RT sequence derived from patient plasma (clone D10), which contained K101E+G190S. 2010 Virology Result HIV G190S;G190S;K101E;K101E 89;229;83;223 94;234;88;228 RT;RT 36;154 38;156 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. In order to further study the role of other RT coding sequences on the phenotypes of the D10 clinical RT sequence, we separately back-mutated the (M41L+T215Y) and K101E mutations in the D10 RT to the corresponding wild-type sequences. 2010 Virology Result HIV K101E;M41L;T215Y 163;147;152 168;151;157 RT;RT;RT 44;102;190 46;104;192 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. In order to understand the effects of the nucleoside resistance mutations M41L+T215Y present in the D10 RT, we introduced these two mutations into NL4-3 containing K101E+G190S. 2010 Virology Result HIV G190S;K101E;M41L;T215Y 170;164;74;79 175;169;78;84 RT 104 106 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. In the absence of EFV, L74V substantially improved the replication fitness of (K101E+G190S) in an NL4-3 RT backbone in the absence of drug. 2010 Virology Result HIV G190S;K101E;L74V 85;79;23 90;84;27 RT 104 106 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. In the absence of EFV, NL4-3 virus containing the D10 RT sequence was somewhat more fit than K101E+G190S in an NL4-3 RT backbone. 2010 Virology Result HIV G190S;K101E 99;93 104;98 RT;RT 54;117 56;119 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K101E reduces the replication fitness of G190S, except in the presence of high EFV concentrations. 2010 Virology Result HIV G190S;K101E 41;0 46;5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. No reduction in fitness of the L74V + (K101E+G190S) triple mutant relative to (K101E+G190S) was observed in the presence of increasing EFV concentrations, as was seen with the ([M41L+T215Y] + [K101E+G190S]) mutant (PRR of triple = 1.40+-0.16 at 1200 nM EFV). 2010 Virology Result HIV G190S;G190S;G190S;K101E;K101E;K101E;L74V;M41L;T215Y 45;85;199;39;79;193;31;178;183 50;90;204;44;84;198;35;182;188 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Of interest is that at least one clinical isolate in that study also contained K101E and G190S. 2010 Virology Result HIV G190S;K101E 89;79 94;84 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Of interest is that removal of (M41L+T215Y) enhanced the degree of EFV-dependent stimulation relative to the original D10 RT sequence, indicating that these nucleoside resistance mutations did have some suppressive effect on EFV-dependent stimulation when combined with (K101E+G190S) in the D10 backbone. 2010 Virology Result HIV G190S;K101E;M41L;T215Y 277;271;32;37 282;276;36;42 RT 122 124 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Since K101E has been observed in combination with G190S in patients failed EFV, we wanted to determine the effect of the addition of K101E on the replication of G190S. 2010 Virology Result HIV G190S;G190S;K101E;K101E 50;161;6;133 55;166;11;138 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Studies using PHA- and IL-2-stimulated primary human PBMCs confirmed that the properties of the K101E+G190S mutant are also observed in primary cells (data not shown). 2010 Virology Result HIV G190S;K101E 102;96 107;101 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Surprisingly, when reviewing the drug resistance data, we found that the K101E+G190S double mutant's replication was 2.0 - 2.5 fold higher in 200 - 800 nM of EFV than in the absence of drug. 2010 Virology Result HIV G190S;K101E 79;73 84;78 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The above studies suggested that RT polymorphisms present in the D10 clinical RT sequence allowed the persistence of the EFV-dependent stimulation of virus replication conferred by (K101E+G190S) despite the presence of (M41L+T215Y). 2010 Virology Result HIV G190S;K101E;M41L;T215Y 188;182;220;225 193;187;224;230 RT;RT 33;78 35;80 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The combination of K101E and G190S reduced replication fitness in the absence of EFV to a much greater extent than either mutation alone (PRR=0.57+-0.06 versus G190S), but the fitness deficit of the double mutant relative to G190S was reversed at concentrations of EFV exceeding 200 nM. 2010 Virology Result HIV G190S;G190S;G190S;K101E 29;160;225;19 34;165;230;24 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The IC50 of K101E+G190S was substantially higher than either single mutant, as expected from the results of growth competition assays in the presence of EFV (Table 1). 2010 Virology Result HIV G190S;K101E 18;12 23;17 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The K101E mutation alone-reduced HIV-1 replication fitness by 20% compared to wild type (PRR=0.81+-0.05) and had slightly increased fitness relative to G190S (PRR=1.07+-0.01). 2010 Virology Result HIV G190S;K101E 152;4 157;9 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The K101E+G190S mutant in an NL4-3 backbone demonstrates EFV-dependent stimulation of virus replication. 2010 Virology Result HIV G190S;K101E 10;4 15;9 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The magnitude of improvement in relative fitness was greater than conferred by the addition of (M41L+T215Y), since the L74V + (K101E+G190S) triple mutant's fitness was as good as, if not better than, G190S alone in the absence of EFV. 2010 Virology Result HIV G190S;G190S;K101E;L74V;M41L;T215Y 133;200;127;119;96;101 138;205;132;123;100;106 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The peak p24 concentration for the K101E+G190S double mutant in 400 nM EFV was almost ten-fold greater than the p24 concentration of G190S in a similar concentration of EFV. 2010 Virology Result HIV G190S;G190S;K101E 41;133;35 46;138;40 p24;p24 9;112 12;115 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The phenotype of EFV-dependent stimulation of virus replication was abolished by mutating K101E to wild-type. 2010 Virology Result HIV K101E 90 95 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. There are no published reports of NNRTIs stimulating HIV-1 replication, although the M230L mutant was reported to display this property in presented but unpublished work (Huang W., Parkin N.T., Lie, Y.S., et al. 2010 Virology Result HIV M230L 85 90 NNRTI 34 40 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. These data indicate that L74V fully compensates for the replication fitness impairment conferred by K101E in combination with G190S. 2010 Virology Result HIV G190S;K101E;L74V 126;100;25 131;105;29 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. These studies demonstrated that in the D10 clinical RT backbone, K101E reduced replication fitness. 2010 Virology Result HIV K101E 65 70 RT 52 54 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. This clinical RT sequence also contained the nucleoside resistance mutations M41L+T215Y, in addition to 28 coding changes in RT compared to NL4-3 (Table 2). 2010 Virology Result HIV M41L;T215Y 77;82 81;87 RT;RT 14;125 16;127 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. This hypothesis was confirmed by drug susceptibility assays showing that (M41L+T215Y) reduced the EFV IC50 of (K101E+G190S) in an NL4-3 RT backbone (Table 1, p<0.0001) and abolished the EFV-dependent stimulation of viral growth phenotype of (K101E+G190S). 2010 Virology Result HIV G190S;G190S;K101E;K101E;M41L;T215Y 117;248;111;242;74;79 122;253;116;247;78;84 RT 136 138 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Thus, the polymorphisms in D10 appear to augment the EFV-dependent growth stimulation conferred by K101E, but do not directly contribute to EFV-dependent growth stimulation in the absence of this mutation. 2010 Virology Result HIV K101E 99 104 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Thus, the presence of (M41L+T215Y) at least partially explains the improved fitness of NL4-3 containing the D10 RT relative to NL4-3 (K101E+G190S) in the absence of drug, but is not consistent with the observed stimulation of replication of the D10-NL4-3 virus by EFV. 2010 Virology Result HIV G190S;K101E;M41L;T215Y 140;134;23;28 145;139;27;33 RT 112 114 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Using this assay, concentrations of EFV that stimulated replication of K101E+G190S, as defined by p24 antigen production, also increased the number of infected cells compared to the no drug control (data not shown). 2010 Virology Result HIV G190S;K101E 77;71 82;76 p24 98 101 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We also evaluated whether another nucleoside resistance mutation, L74V, might affect the replication of (K101E+G190S), since L74V has been shown to improve the replication fitness of at least two other NNRTI-resistant mutants, G190E and (K103N+L100I). 2010 Virology Result HIV G190E;G190S;K101E;K103N;L100I;L74V;L74V 227;111;105;238;244;66;125 232;116;110;243;249;70;129 NNRTI 202 207 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We also measured replication of the G190S and K101E+G190S mutants using a previously published replication assay in which a reporter gene product expressed by HIV-infected cells is detected by flow cytometry. 2010 Virology Result HIV G190S;G190S;K101E 36;52;46 41;57;51 HIV infections 159 171 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We compared the relative fitness of recombinant viruses carrying K101E or G190S alone and in combination, in an NL4-3 backbone, using multiple-cycle growth competition assays in PM1 cells. 2010 Virology Result HIV G190S;K101E 74;65 79;70 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We confirmed that the M230L mutant in an NL4-3 backbone does replicate better in the presence of low concentrations of EFV than in the absence of drug; the magnitude of EFV-dependent stimulation is similar to that observed with K101E+G190S, although the peak of growth stimulation occurred at a much lower EFV concentration than K101E+G190S (10 nM vs. 2010 Virology Result HIV G190S;G190S;K101E;K101E;M230L 234;335;228;329;22 239;340;233;334;27 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We have previously shown that the relative fitness of G190S is 40% reduced relative to wild type. 2010 Virology Result HIV G190S 54 59 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We observed that M41L+T215Y improved the replication fitness of the NNRTI-resistant K101E+G190S NL4-3 mutant, although the quadruple mutant still had substantially reduced fitness compared to G190S alone. 2010 Virology Result HIV G190S;G190S;K101E;M41L;T215Y 90;192;84;17;22 95;197;89;21;27 NNRTI 68 73 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. With this level of stimulation, the p24 values of the D10 clone exceeded those of the G190S mutant beginning at an EFV concentration of 200 nM (compare. 2010 Virology Result HIV G190S 86 91 p24 36 39 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Although the SP1-A1T change has not previously been reported in association with BVM resistance, it maps to the same residue as the robust SP1-A1V BVM-resistance mutation. 2010 Retrovirology Result HIV A1T;A1V 17;143 20;146 SP1;SP1 13;139 16;142 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. At the 50 ng/ml BVM concentration, the SP1-V7M virus was capable of replicating, albeit with a significant delay, without acquiring additional amino acid substitutions. 2010 Retrovirology Result HIV V7M 43 46 SP1 39 42 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. However, at the 1 mug/ml concentration, detectable replication was even further delayed and was accompanied by the acquisition of an SP1-A1T substitution. 2010 Retrovirology Result HIV A1T 137 140 SP1 133 136 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. However, in a repeat experiment, replication emerged after 68 days in culture and was accompanied by acquisition of the SP1-A3V mutation (data not shown). 2010 Retrovirology Result HIV A3V 124 127 SP1 120 123 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. However, virus infectivity was clearly inhibited when the WT, SP1-Q6A, -Q6H and -T8A viruses were generated in the presence of BVM. 2010 Retrovirology Result HIV Q6H;T8A;Q6A 72;81;66 75;84;69 SP1 62 65 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. In a repeat experiment, the same pattern of replication and mutation acquisition was observed for the V7M mutant, except that at 1 mug/ml BVM a CA-V230I substitution and the previously characterized SP1-A3V mutation were detected when virus replication emerged after 29 days in culture (data not shown). 2010 Retrovirology Result HIV V230I;V7M;A3V 147;102;203 152;105;206 SP1;Capsid 199;144 202;146 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. In agreement with our previous studies, the SP1-A1V mutant was fully resistant to BVM as it replicated with WT kinetics independent of BVM concentration and did not acquire additional mutations. 2010 Retrovirology Result HIV A1V 48 51 SP1 44 47 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. In contrast, BVM treatment did not reduce the ability of SP1-A1V or -V7A viruses to infect TZM-bl cells. 2010 Retrovirology Result HIV A1V;V7A 61;69 64;72 SP1 57 60 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. In contrast, CA-SP1 processing in SP1-V7A BVM-treated samples was similar to that seen in untreated WT or SP1-A1V samples. 2010 Retrovirology Result HIV A1V;V7A 110;38 113;41 SP1;SP1;SP1;Capsid 16;34;106;13 19;37;109;15 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Infectivity of viruses harboring the SP1-V7M and -T8Delta mutations was only moderately inhibited when produced in the presence of BVM. 2010 Retrovirology Result HIV V7M 41 44 SP1 37 40 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Interestingly, intermediate levels of CA-SP1 processing were observed in SP1-V7M and -T8Delta virions produced from BVM-treated cells. 2010 Retrovirology Result HIV V7M 77 80 SP1;SP1;Capsid 41;73;38 44;76;40 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Interestingly, the CA-V230I substitution occurs frequently in HIV-1 isolates and therefore could represent an additional Gag polymorphism associated with BVM resistance. 2010 Retrovirology Result HIV V230I 22 27 Gag;Capsid 121;19 124;21 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. No replication was detectable for the SP1-Q6A and -Q6H mutants in the presence of either 50 ng/ml or 1 mug/ml BVM. 2010 Retrovirology Result HIV Q6H;Q6A 51;42 54;45 SP1 38 41 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Point mutations at SP1/6-8 were introduced into the infectious HIV-1 molecular clone pNL4-3 to generate pNL4-3 SP1-Q6A, -Q6H, -V7A, -V7 M, -T8A and -T8Delta. 2010 Retrovirology Result HIV Q6H;T8A;V7A;Q6A 121;140;127;115 124;143;130;118 SP1;SP1 19;111 22;114 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Replication of SP1-T8Delta was significantly delayed at the 50 ng/ml BVM concentration and was only detected upon acquisition of the SP1-A1V BVM-resistance mutation. 2010 Retrovirology Result HIV A1V 137 140 SP1;SP1 15;133 18;136 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Similar levels of CA-SP1 were observed in the SP1-Q6A, -Q6H and -T8A BVM-treated samples. 2010 Retrovirology Result HIV Q6H;T8A;Q6A 56;65;50 59;68;53 SP1;SP1;Capsid 21;46;18 24;49;20 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The CA-V230I substitution has previously been reported to be acquired in the context of a CA-L231 MBVM-resistance mutation combined with a mutant PR when propagated in the presence of BVM. 2010 Retrovirology Result HIV V230I 7 12 Capsid;Capsid;PR 4;90;146 6;92;148 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The SP1-T8A virus did not replicate at 50 ng/ml BVM; however, replication of this mutant was detected at 1 mug/ml BVM at day 45 posttransfection and was accompanied by acquisition of the SP1-A3V mutation. 2010 Retrovirology Result HIV A3V;T8A 191;8 194;11 SP1;SP1 4;187 7;190 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The SP1-V7A mutation exhibited resistance to BVM as its replication was only moderately delayed with increasing BVM concentration and it replicated without acquiring additional mutations. 2010 Retrovirology Result HIV V7A 8 11 SP1 4 7 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The SP1-V7A substitution has not been observed in previous in vitro BVM-resistance selection studies. 2010 Retrovirology Result HIV V7A 8 11 SP1 4 7 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. This panel includes both alanine-scanning mutations across the residues of interest and several observed Gag polymorphisms (SP1-Q6H, -V7A, -V7 M, -T8A, and -T8Delta). 2010 Retrovirology Result HIV T8A;V7A;Q6H 147;134;128 150;137;131 SP1;Gag 124;105 127;108 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Virus release efficiency was not significantly affected, with the exception of the SP1-V7A mutant cultured in the absence of drug, where a 3-fold reduction in virus release efficiency was observed (data not shown). 2010 Retrovirology Result HIV V7A 87 90 SP1 83 86 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. WT pNL4-3, which contains the QVT motif at SP1/6-8, was used as a BVM-susceptible virus and the previously characterized SP1-A1V mutant served as a prototypical BVM-resistant virus. 2010 Retrovirology Result HIV A1V 125 128 SP1;SP1 43;121 46;124 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. WT virus was fully inhibited at 1 mug/ml BVM but developed BVM resistance after 47 days in the presence of 50 ng/ml BVM by acquisition of an SP1-V7A mutation. 2010 Retrovirology Result HIV V7A 145 148 SP1 141 144 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. A Student test that was used to derive P values showed there are not statistical differences between the IN WT and Y143C, and Y143R. 2010 PloS one Result HIV Y143C;Y143R 115;126 120;131 IN 105 107 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. All three enzymes, IN WT, IN Y143C and IN Y143R, were sensitive to RAL (Figure 4A) with an IC50 for 3'-end processing of 0.4 microM, 0.9 microM (FC = 2.25) and 1.2 microM respectively (FC = 3). 2010 PloS one Result HIV Y143C;Y143R 29;42 34;47 IN;IN;IN 19;26;39 21;28;41 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Clonal analysis also showed that the T97A and G163R mutations could be present in association with Y143R but could also be selected in the absence of Y143R (in patients 2 and 3). 2010 PloS one Result HIV G163R;T97A;Y143R;Y143R 46;37;99;150 51;41;104;155 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. IC50 was around 0.3 microM for IN WT and IN Y143C (Figure 5). 2010 PloS one Result HIV Y143C 44 49 IN;IN 31;41 33;43 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In all three patients, the initial selection of the N155H mutation was followed by its disappearance and replacement by a pattern comprising the Y143H/R/C mutations with other mutations (T97A in 3 patients, L74M in 2 patients and G163R and S230R in one patient each); RAL was stopped between months 6 and 12 in patient 1, with disappearance of the selected mutations. 2010 PloS one Result HIV G163R;L74M;N155H;S230R;T97A;Y143C;Y143H;Y143R 230;207;52;240;187;145;145;145 235;211;57;245;192;154;154;154 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In all three patients, the replacement over time of the N155H pattern by the Y143R/C pattern was confirmed by clonal sequences (Table S1). 2010 PloS one Result HIV N155H;Y143C;Y143R 56;77;77 61;84;84 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In order to study the dynamics of replacement and the linkage between mutations in patients presenting a switch from the N155H to the Y143C/H/R pattern, we cloned and sequenced the viral populations from the three patients at baseline RAL and during follow-up. 2010 PloS one Result HIV N155H;Y143C;Y143H;Y143R 121;134;134;134 126;143;143;143 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In particular for enzymes concentrations below 400 nM, the activity of the mutants was decreased in comparison to that of the wild-type enzyme, with a slightly lower activity for mutation Y143R (Figure 3). 2010 PloS one Result HIV Y143R 188 193 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In patient 1, N155H was present in 39% of clones at M1 and in 9% of clones at M3, whereas Y143C was absent at M1 and present in 91% of clones at M3. 2010 PloS one Result HIV N155H;Y143C 14;90 19;95 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In patient 2, the percentages of clones with the N155H/R mutations and with the Y143C mutation were respectively 84% and 9% at M3, and 0% and 66% at M6. 2010 PloS one Result HIV N155H;N155R;Y143C 49;49;80 56;56;85 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In patient 3, the N155H mutation was detected only at M3 and in 72% of clones, whereas Y143R was present only at M6 and in 47% of clones. 2010 PloS one Result HIV N155H;Y143R 18;87 23;92 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In samples with the Y143C/H/R mutations, the median baseline RAL FC was 24.83 (range 5.87-51.95) and the median baseline EVG FC was 3 (range 1.56-9.57). 2010 PloS one Result HIV Y143C;Y143H;Y143R 20;20;20 29;29;29 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Mutations Y143C and Y143R were introduced into the IN gene and recombinant enzymes were expressed and purified according to standard procedures used in the laboratory. 2010 PloS one Result HIV Y143C;Y143R 10;20 15;25 IN 51 53 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. On the contrary, the Y143R mutation conferred a decreased sensitivity to RAL (FC = 2). 2010 PloS one Result HIV Y143R 21 26 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. On the other hand, the strand transfer activities of the mutant enzymes were severely impaired, since only 30% (IN Y143C) and 50% (IN Y143R) of the activity of the wild type was measured at a concentration of 250 nM of enzyme (Figure 2B). 2010 PloS one Result HIV Y143C;Y143R 115;134 120;139 IN;IN 112;131 114;133 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Several polymorphic mutations previously related to INI resistance were present at D0: V72I was present in patients 1 and 3, V151I in patient 2, and I203M in patient 1. 2010 PloS one Result HIV I203M;V151I;V72I 149;125;87 154;130;91 IN 52 55 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The strand transfer function of the mutant recombinant integrases (particularly Y143C) in the concerted integration reaction was not as defective as when the same enzymes were used in the strand transfer reaction with pre-processed DNA. 2010 PloS one Result HIV Y143C 80 85 IN 55 65 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The two samples with the N155H had low RAL FC (1.07 and 1.72) and low EVG FC (2. 2010 PloS one Result HIV N155H 25 30 20453629 Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa. Among the 35 viremic patients failing a second-line regimen, 29% (n=10), 54% (n=19) and 6% (n=2) patients had mutations associated with NRTI resistance (mainly M184V/I, n=9), NNRTI resistance (mainly K103N, n=15), and major PI mutations respectively. 2010 AIDS (London, England) Result HIV K103N;M184I;M184V 200;160;160 205;167;167 NNRTI;NRTI;PI 175;136;224 180;140;226 20453629 Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa. Of the 94 viremic patients on the first-line regimen, 64% (n=60), 81% (n=76), and 2% (n=2) had evidence of NRTI, NNRTI, and PI resistance respectively; M184V/I and K103N were the most prevalent mutations (62% (n=58) and 48% (n=45) respectively), and 16% (n=15) had TAMs. 2010 AIDS (London, England) Result HIV K103N;M184I;M184V 164;152;152 169;159;159 NNRTI;NRTI;PI 113;107;124 118;111;126 20453629 Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa. The two patients with PI mutations harboured either Q58E, L90M or N88S. 2010 AIDS (London, England) Result HIV L90M;N88S;Q58E 58;66;52 62;70;56 PI 22 24 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Although V179F covaried with Y181C, it is not shown in Figure 2 because it occurred too uncommonly to be accurately placed by multidimensional scaling. 2010 The Journal of antimicrobial chemotherapy Result HIV V179F;Y181C 9;29 14;34 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Among the sequences from 782 women treated with a single dose of nevirapine, the most frequently observed mutations were K103N (28%), Y181C (15%), Y188C (6%), G190A (5%) and E138A (4%). 2010 The Journal of antimicrobial chemotherapy Result HIV E138A;G190A;K103N;Y181C;Y188C 174;159;121;134;147 179;164;126;139;152 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Another notable, though weaker, positive correlation exists between K65R and Y181C. 2010 The Journal of antimicrobial chemotherapy Result HIV K65R;Y181C 68;77 72;82 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Figure 1a shows the 16 mutations that occurred significantly more commonly in efavirenz-exposed individuals (L100I, K101P, K103N, V106I/M, V108I, V179D, Y188H/L, G190E/S/Q, P225H, F227Y, M230L and K238T), and Figure 1b shows the 12 that occurred significantly more commonly in nevirapine-exposed individuals (A98G, K101E, K103S, V106A, E138A, T139R, Y181C/I/V, Y188C, G190A and H221Y). 2010 The Journal of antimicrobial chemotherapy Result HIV A98G;E138A;F227Y;G190A;G190E;G190Q;G190S;H221Y;K101E;K101P;K103N;K103S;K238T;L100I;M230L;P225H;T139R;V106A;V106I;V106M;V108I;V179D;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 309;336;180;368;162;162;162;378;315;116;123;322;197;109;187;173;343;329;130;130;139;146;350;350;350;361;153;153 313;341;185;373;171;171;171;383;320;121;128;327;202;114;192;178;348;334;137;137;144;151;359;359;359;366;160;160 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. G190A (n = 9), Y181C (n = 8), V108I (n = 6), K101E (n = 4), H221Y (n = 4) and F227L (n = 4) were the most common mutations among these 29 pairs. 2010 The Journal of antimicrobial chemotherapy Result HIV F227L;H221Y;K101E;V108I;Y181C;G190A 78;60;45;30;15;0 83;65;50;35;20;5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. L100I was significantly associated with K103N, and K101P was significantly associated with K103S. 2010 The Journal of antimicrobial chemotherapy Result HIV K101P;K103N;K103S;L100I 51;40;91;0 56;45;96;5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. M230L was most strongly associated with K103N (P = 0.003 uncorrected, not significant following correction for multiple comparisons). 2010 The Journal of antimicrobial chemotherapy Result HIV K103N;M230L 40;0 45;5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Sequences from 213 individuals (27%) had at least one etravirine RAM, including 118 (15%) with at least one major etravirine RAM (115 with Y181C, 1 with L100I and 1 with both). 2010 The Journal of antimicrobial chemotherapy Result HIV L100I;Y181C 153;139 158;144 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The 57 clusters could be characterized as follows: (i) 3 clusters of five mutations: A98G/K101E/V108I/Y181C/G190A, K101E/V108I/Y181C/G190A/H221Y and K103H/V108I/Y181C/G190A/H221Y, each of which contains within it 5 clusters of four mutations and 10 clusters of three mutations (n = 48); (ii) 3 additional clusters of four mutations: K101H/V108I/Y181C/G190A, K101N/K103H/Y181C/G190A and V108I/G190A/H221Y/F227L, each of which contains 4 clusters of three mutations (n = 15); and (iii) 7 additional clusters of three mutations: K101E/Y181C/G190S, K101H/Y181C/G190S, K103N/E138Q/K238T, S105T/V106A/F227L, V106A/G190A/F227L, V106M/G190A/F227L and V179F/Y181C/G190A. 2010 The Journal of antimicrobial chemotherapy Result HIV A98G;E138Q;F227L;F227L;F227L;F227L;G190A;G190A;G190A;G190A;G190A;G190A;G190A;G190A;G190A;G190S;G190S;H221Y;H221Y;H221Y;K101E;K101E;K101E;K101H;K101H;K101N;K103H;K103H;K103N;K238T;S105T;V106A;V106A;V106M;V108I;V108I;V108I;V108I;V108I;V179F;Y181C;Y181C;Y181C;Y181C;Y181C;Y181C;Y181C;Y181C 85;570;404;595;614;633;108;133;167;351;376;392;608;627;655;538;557;139;173;398;90;115;526;333;545;358;149;364;564;576;583;589;602;621;96;121;155;339;386;643;102;127;161;345;370;532;551;649 89;575;409;600;619;638;113;138;172;356;381;397;613;632;660;543;562;144;178;403;95;120;531;338;550;363;154;369;569;581;588;594;607;626;101;126;160;344;391;648;107;132;166;350;375;537;556;654 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The first principal coordinate accounts for 36% of the total inertia and separates the predominantly nevirapine-selected mutations A98G, K101E, V108I, Y181C, G190A and H221Y from the other NNRTI resistance mutations. 2010 The Journal of antimicrobial chemotherapy Result HIV A98G;G190A;H221Y;K101E;V108I;Y181C 131;158;168;137;144;151 135;163;173;142;149;156 NNRTI 189 194 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The major etravirine RAM Y181C was significantly associated with G190A, H221Y, V108I, A98G, G190S and V179F. 2010 The Journal of antimicrobial chemotherapy Result HIV A98G;G190A;G190S;H221Y;V108I;V179F;Y181C 86;65;92;72;79;102;25 90;70;97;77;84;107;30 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The most common mutations in sequences from efavirenz-experienced individuals were K103N (72% of the sequences), L100I (14%), P225H (11%), V108I (11%), G190A (9.5%), Y188L (9.3%), G190S (7.2%), K101E (7.2%) and V106M (7.0%). 2010 The Journal of antimicrobial chemotherapy Result HIV G190A;G190S;K101E;K103N;L100I;P225H;V106M;V108I;Y188L 152;180;194;83;113;126;211;139;166 157;185;199;88;118;131;216;144;171 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The most common mutations in sequences from nevirapine-experienced individuals were Y181C (46% of the sequences), K103N (43%), G190A (26%), H221Y (12%) and K101E (11%). 2010 The Journal of antimicrobial chemotherapy Result HIV G190A;H221Y;K101E;K103N;Y181C 127;140;156;114;84 132;145;161;119;89 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The NNRTI-associated mutation A98G was also strongly positively correlated (corrected P < 0.01) with the thymidine analogue mutations M41L, D67N, L210W and T215F/Y. 2010 The Journal of antimicrobial chemotherapy Result HIV A98G;D67N;L210W;M41L;T215F;T215Y 30;140;146;134;156;156 34;144;151;138;163;163 NNRTI 4 9 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The remaining six triplets contain K103N in combination with a pair of covarying mutations. 2010 The Journal of antimicrobial chemotherapy Result HIV K103N 35 40 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The second principal coordinate accounts for 25% of the total inertia and separates out V106A and F227L. 2010 The Journal of antimicrobial chemotherapy Result HIV F227L;V106A 98;88 103;93 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The strongest positive correlations were between the NRTI mutations L74V/I and the NNRTI mutations Y181C and L100I. 2010 The Journal of antimicrobial chemotherapy Result HIV L100I;L74I;L74V;Y181C 109;68;68;99 114;74;74;104 NNRTI;NRTI 83;53 88;57 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The third principal component accounts for 15% of the total inertia and separates K103N and its associated mutations (L100I, P225H and K238T) from G190S and Y188L. 2010 The Journal of antimicrobial chemotherapy Result HIV G190S;K103N;K238T;L100I;P225H;Y188L 147;82;135;118;125;157 152;87;140;123;130;162 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Y188C was the only mutation to occur significantly more frequently among the single-dose nevirapine sequences (6%) than among the full dataset of 1510 nevirapine-experienced individuals (2%). 2010 The Journal of antimicrobial chemotherapy Result HIV Y188C 0 5 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Each wildtype Env and its I309L mutant displayed comparable replication kinetics and p24 levels (Fig 2A and Suppl. 2010 Virology Result HIV I309L 26 31 p24;Env 85;14 88;17 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. For 9 of the 11 Envs, I309L resulted in an increase in sensitivity compared against wildtype at the highest concentration of sCD4 (100nM). 2010 Virology Result HIV I309L 22 27 Env 16 20 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. I309L was created in a representative panel of diverse subtype C Envs. 2010 Virology Result HIV I309L 0 5 Env 65 69 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. If I309L induces conformationally based changes in gp120 that increase exposure of the CD4bs, we hypothesized that other Env domains could also be affected. 2010 Virology Result HIV I309L 3 8 gp120;Env 51;121 56;124 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. In 6 of the 11 Envs, there was an increase in sensitivity to anti-V3 mediated neutralization with the I309L mutation. 2010 Virology Result HIV I309L 102 107 Env 15 19 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Nevertheless, using p24 level at day 13 post-infection for comparison, the I309L Envs overall replicated to moderately higher levels than their wildtype counterparts. 2010 Virology Result HIV I309L 75 80 p24;Env 20;81 23;85 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Overall the difference between the wildtype and I309L Envs reached the borderline of statistical significance in a paired analysis. 2010 Virology Result HIV I309L 48 53 Env 54 58 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Overall, however, infectivity of JC.10 cells was decreased by approximately 10-fold for all Envs, compared to the JC.53 cells (high CCR5, high CD4), suggesting that the wildtype and I309L Envs were equally dependent on CCR5 for entry into JC.10 cells. 2010 Virology Result HIV I309L 182 187 Env;Env 92;188 96;192 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Overall, viral infectivity was significantly lower with the I309L mutation at both 100nM and 20nM concentrations of sCD4. 2010 Virology Result HIV I309L 60 65 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Ten of the eleven Envs, with and without I309L, were transferred into a replication competent NL4.3 proviral backbone and used to infect PBMC enriched for CD4 T cells by CD8 depletion. 2010 Virology Result HIV I309L 41 46 Env 18 22 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L Envs required higher concentrations of anti-CD4 to inhibit infection (with a higher IC50) than wildtype, confirming their more efficient utilization of the CD4 receptor. 2010 Virology Result HIV I309L 4 9 Env 10 14 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L mutation confers increased entry into a cell line expressing low CD4. 2010 Virology Result HIV I309L 4 9 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L mutation confers increased sensitivity to sCD4. 2010 Virology Result HIV I309L 4 9 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L mutation did not, therefore, "pre-trigger" the coreceptor binding domain, leading to CD4 independence, as has been described for subtype B Envs carrying non-consensus residues at position 309. 2010 Virology Result HIV I309L 4 9 Env 149 153 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L mutation does not decrease replication in primary CD4 T cells. 2010 Virology Result HIV I309L 4 9 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L mutation leads to a moderate enhancement of replication in monocyte-derived macrophages. 2010 Virology Result HIV I309L 4 9 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L mutation moderately increased sensitivity to monoclonal antibodies directed against V3 and a CD4-induced epitope. 2010 Virology Result HIV I309L 4 9 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L mutation was created in the V3 domain of each of the 11 Envs. 2010 Virology Result HIV I309L 4 9 Env 66 70 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The I309L substitution, however, led to an almost universal increase in sCD4 sensitivity, although the magnitude varied between Envs (Fig 5A). 2010 Virology Result HIV I309L 4 9 Env 128 132 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. There was one pair of Envs from subject 221 for which the I309L did appear to decrease infectivity, although this effect may be due to an inherent property of the V3 loop (perhaps the D321, see. 2010 Virology Result HIV I309L 58 63 Env 22 26 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Therefore, this time point was used to compare the overall replication between paired sets of wildtype and I309L mutant Envs. 2010 Virology Result HIV I309L 107 112 Env 120 124 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. These cell lines were infected with pseudoviruses created by expressing the wildtype or I309L mutant Envs with an HIV-1 env-deficient backbone that encodes luciferase. 2010 Virology Result HIV I309L 88 93 Env;Env 101;120 105;123 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. These later Envs allowed us to evaluate the effects of the I309L mutation specifically within Envs known to have adapted to Nab immune pressure during natural infection. 2010 Virology Result HIV I309L 59 64 Env;Env 12;94 16;98 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. This result demonstrates that I309L-containing Envs are replication competent in activated CD4 T cells, and suggests that the strong conservation of I309 is not due to a detrimental effect on viral replication, at least as measured by this in vitro assay. 2010 Virology Result HIV I309L 30 35 Env 47 51 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Thus, although both I309L and wildtype Envs were inefficient at infecting cells with limiting levels of CD4, the I309L Envs consistently had higher relative infectivity, suggesting more efficient binding to CD4 and/or increased exposure of the CD4bs. 2010 Virology Result HIV I309L;I309L 20;113 25;118 Env;Env 39;119 43;123 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. To ensure that the I309L mutation had not reverted, the V3 domain of each mutant virus was sequenced using virion-associated RNA in supernatant collected at day 10 during one experiment (data not shown). 2010 Virology Result HIV I309L 19 24 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Under the condition of high CD4 and limited CCR5, there was no statistically significant difference between the wildtype and I309L Envs in ability to enter the JC.10 cells (Fig 4A). 2010 Virology Result HIV I309L 125 130 Env 131 135 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. We next investigated whether the I309L Envs were also more susceptible to sCD4-triggering of the coreceptor binding site, which contains an epitope recognized by the monoclonal antibody 17b. 2010 Virology Result HIV I309L 33 38 Env 39 43 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. We therefore evaluated whether I309L altered in vitro replication in MDM cultures. 2010 Virology Result HIV I309L 31 36 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. We therefore evaluated whether the I309L change would be detrimental to replication in activated CD4 T cells. 2010 Virology Result HIV I309L 35 40 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. When CD4 levels were reduced, however, the I309L containing Envs consistently had higher relative infectivity in the RC.49 cells, ranging from a 1.1- to an 18.6-fold increase over the matched wildtype Env. 2010 Virology Result HIV I309L 43 48 Env;Env 60;201 64;204 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Each sample had both K65R and M184V; six samples had 65R present as a mixture with wild-type K65, and three of these six contained a mixture of 184V with wild-type M184. 2010 Antiviral therapy Result HIV K65R;M184V 21;30 25;35 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Five of 13 sequences had K70E from Patient #5. 2010 Antiviral therapy Result HIV K70E 25 29 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. For ddI, TNV, and ABC, the mean IC50 values for K65R/M184V double-mutants were significantly higher than for M184V single-mutants (p <0.001). 2010 Antiviral therapy Result HIV K65R;M184V;M184V 48;53;109 52;58;114 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. K65R was detected in 105 (51%) sequences. 2010 Antiviral therapy Result HIV K65R 0 4 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. K65R/M184I double-mutant and wild-type were detected only once each. 2010 Antiviral therapy Result HIV M184I;K65R 5;0 10;4 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Of the 204 sequences, 179 (88%) contained M184V and 22 (11%) contained M184I. 2010 Antiviral therapy Result HIV M184I;M184V 71;42 76;47 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Of twelve clones studied, five were M184V single-mutants, one was a M184I single-mutant, and six were K65R/M184V double-mutants. 2010 Antiviral therapy Result HIV K65R;M184I;M184V;M184V 102;68;36;107 106;73;41;112 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Samples were further categorized as having "pure" M184V and K65R (three samples) or as M184V and a "mixture" of K65R and wild-type K65 (six samples). 2010 Antiviral therapy Result HIV K65R;K65R;M184V;M184V 60;112;50;87 64;116;55;92 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Specifically, for K65R/M184V double-mutants versus M184V single-mutants, the mean IC50 for ddI was 14.29+-4.93 muM (fold-resistance=3.8) versus 5.11+-2.68 muM (fold-resistance=1.4), for TNV 7.10+-3.37 muM (fold-resistance=1.6) versus 2.37+-0.91 muM (fold-resistance=0.5) and for ABC 68.25+-18.37 muM (fold-resistance=7.7) versus 20.78+-7.41 muM (fold-resistance=2.4). 2010 Antiviral therapy Result HIV K65R;M184V;M184V 18;23;51 22;28;56 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. The K65R single-mutant was detected in only 2/204 (1%) sequences. 2010 Antiviral therapy Result HIV K65R 4 8 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. The K65R/M184V double-mutant was detected in 8/9 patients. 2010 Antiviral therapy Result HIV K65R;M184V 4;9 8;14 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. The most common sequence was the K65R/M184V double-mutant in 102/204 (50%), followed by M184V single-mutant in 77/204 (38%), and M184I single-mutant in 21/204 (10%). 2010 Antiviral therapy Result HIV K65R;M184I;M184V;M184V 33;129;38;88 37;134;43;93 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. 2b), although the core yield of the S16A/P17A variant from HEK293 cells was very similar to that of WT HIV-1, and the phenotypes of the CA core were normal. 2010 The Journal of biological chemistry Result HIV P17A;S16A 41;36 45;40 Capsid 136 138 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. 4c, p < 0.01) and catalytically inactived the W34A/K63A Pin1 mutant. 2010 The Journal of biological chemistry Result HIV K63A;W34A 51;46 55;50 PI 56 58 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Assuming that glutamic acid mimics the negative charge of phosphorylated Ser16 in only a fraction of the CA protein in a viral core, the results obtained for S16E or S16A suggest that phosphorylation at Ser16 plays a critical role in maintaining viral infectivity. 2010 The Journal of biological chemistry Result HIV S16A;S16E 166;158 170;162 Capsid 105 107 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Furthermore, the levels of the CA protein in the supernatants from MAGIC-5 cells incubated with the S16A/P17A mutant virus were lower than those detected in the cells infected with WT virus. 2010 The Journal of biological chemistry Result HIV P17A;S16A 105;100 109;104 Capsid 31 33 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Furthermore, to determine whether the lack of infectivity of S16A/P17A was due to a defect in the reverse transcription process, we carried out a viral entry assay and quantitative real time PCR analysis using primers designed to specifically amplify early or late products of reverse transcription. 2010 The Journal of biological chemistry Result HIV P17A;S16A 66;61 70;65 RT;RT 98;277 119;298 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. However, compared with WT, S16A/P17A produced the same level of the early (R/U5) form of the viral cDNA product. 2010 The Journal of biological chemistry Result HIV P17A;S16A 32;27 36;31 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. In contrast, the S16A variant had a decreased infectivity. 2010 The Journal of biological chemistry Result HIV S16A 17 21 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Purified CA cores were diluted with an uncoating assay buffer and incubated with GST-Pin1, heat-denatured, inhibitor-treated, or W34A/K63A GST-Pin1. 2010 The Journal of biological chemistry Result HIV K63A;W34A 134;129 138;133 Capsid;PI;PI 9;85;143 11;87;145 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The amounts of pelletable CA cores in the cells infected with the S16A/P17A mutant virus increased against those detected in the cells infected with WT virus. 2010 The Journal of biological chemistry Result HIV P17A;S16A 71;66 75;70 Capsid 26 28 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The results showed that the S16E variant had the same infectivity as the wild type. 2010 The Journal of biological chemistry Result HIV S16E 28 32 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The S16A/P17A variant also had a markedly decreased infectivity in MAGIC-5 cells. 2010 The Journal of biological chemistry Result HIV P17A;S16A 9;4 13;8 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The S16T variant showed a remarkably decreased infectivity compared with the WT virus. 2010 The Journal of biological chemistry Result HIV S16T 4 8 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The viral entry assay indicated that the entry levels of S16A/P17A and WT were the same because the amounts of S16A/P17A CA protein in subcellular fractions were very similar to that of WT CA protein. 2010 The Journal of biological chemistry Result HIV P17A;P17A;S16A;S16A 62;116;57;111 66;120;61;115 Capsid;Capsid 121;189 123;191 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. These results suggest that the infectivity defect of the S16A/P17A variant is linked to a dysfunction of the uncoating process. 2010 The Journal of biological chemistry Result HIV P17A;S16A 62;57 66;61 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. To examine whether the phenotype of the S16A variant was specific to the selected amino acid changes, we produced another variant with a phosphorylatable amino acid residue, changing Ser to Thr (S16T). 2010 The Journal of biological chemistry Result HIV S16A;S16T 40;195 44;199 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. To further examine whether the infectivity defect of the S16A/P17A variant is linked to a dysfunction of uncoating, cell-based fate-of-capsid uncoating assay developed by Sodroski's group was performed. 2010 The Journal of biological chemistry Result HIV P17A;S16A 62;57 66;61 Capsid 135 141 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. To further investigate why Ser16 in a fraction of the CA protein in the virion needs to be phosphorylated, we generated another variant (S16A/P17A) because single-point mutations of Ser16 in the Ser16-Pro17 motif may provide an alternate binding site for conventional peptidyl-prolyl cis-trans isomerases, such as cyclophilins, or FK-506-binding proteins, which catalyze the cis-trans isomerization of Xaa-Pro peptide bonds (where Xaa is the preceding amino acid) in oligopeptides or proteins. 2010 The Journal of biological chemistry Result HIV P17A;S16A 142;137 146;141 Capsid 54 56 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. To study the role of the phosphorylated Ser16 that precedes Pro, we replaced Ser16 with glutamic acid (S16E) or alanine (S16A) to mimic phosphorylated or unphosphorylated Ser, respectively. 2010 The Journal of biological chemistry Result HIV S16A;S16E;S16E 121;103;77 125;107;101 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Considering specific TDRs that could impact virologic response to the N(t)RTI backbone, TDF/FTC, used in the study, 9 (6.4%) of the subjects had M184V/I identified by UDS at baseline. 2010 PloS one Result HIV M184I;M184V 145;145 152;152 NRTI 70 77 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Of the 141 subjects with a UDS result, 35 (24.8%) had a nucleoside(tide) reverse transcriptase inhibitor N(t)RTI(s) TDR; 26 of these had a thymidine analog mutation (TAM), 9 had a M184V/I, and 2 had a variant with a K65R. 2010 PloS one Result HIV K65R;M184I;M184V 216;180;180 220;187;187 RT;NRTI 73;105 94;112 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Seven of 9 M184V/I were at <20% levels and were not detected by standard genotyping. 2010 PloS one Result HIV M184V 11 18 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Six of the 9 experienced VF; 4 of these also had TAMs, and 1 had K65R+TAMs (Table 3). 2010 PloS one Result HIV K65R 65 69 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Sixteen subjects (11.3%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) TDR; of these, 15 had one or more of K103N, Y181C/I or G190A/E. 2010 PloS one Result HIV G190A;G190E;K103N;Y181C;Y181I 139;139;121;128;128 146;146;126;135;135 NNRTI;NNRTI 29;77 65;82 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Specific TDR patterns and levels for subjects with a M184V/I and K65R are shown in Table 4. 2010 PloS one Result HIV K65R;M184I;M184V 65;53;53 69;60;60 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Three (2.1%) subjects had M184V and multiple TAMs, and all were VF; 2 subjects had a K65R at baseline by UDS (1 VF and 1 VS) (Table 3). 2010 PloS one Result HIV K65R;M184V 85;26 89;31 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. For example, whereas the IC50 for nevirapine was increased >75-fold for both Y181C and K103N HIV-1 RT relative to the WT enzyme, the IC50 values for all of the NAIM analogs against the Y181C and K103N RTs was decreased less than 2-fold relative to the WT enzyme. 2010 Letters in drug design & discovery Result HIV K103N;K103N;Y181C;Y181C 87;195;77;185 92;200;82;190 RT;RT 99;201 101;204 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. In this regard, the orientation of the phenyl groups as hydrophobic moieties into the hydrophobic pockets of NNRTI-BP and the imidazole nucleus as the hydrophilic moiety oriented towards the least hydrophobic portion may be responsible for the observed activity of this analog against RTs containing Y181C or K103N. 2010 Letters in drug design & discovery Result HIV K103N;Y181C 309;300 314;305 NNRTI;RT 109;285 114;288 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. Surprisingly, and in contrast to nevirapine, all of the NAIMs analogs retained good activity against HIV-1 RT containing either the K103N or Y181C mutations. 2010 Letters in drug design & discovery Result HIV K103N;Y181C 132;141 137;146 RT 107 109 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. For utilization of dGTP, the K65A substitution caused a greater fold change in kpol compared to wild-type. 2010 Journal of molecular biology Result HIV K65A 29 33 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. From the more conservative G:T mismatch K65R and K65A again showed a small reduction in kpol compared to the wild-type enzyme. 2010 Journal of molecular biology Result HIV K65A;K65R 49;40 53;44 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. However, in absolute terms, the K65R RT is considerably less efficient at misinsertion compared to the wild-type enzyme (WT(kpol/Kd)Incorrect / K65R(kpol/Kd)Incorrect = 2.5 to 3.6-fold), largely due to the reduction in kpol (Table 1). 2010 Journal of molecular biology Result HIV K65R;K65R 32;144 36;148 RT 37 39 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. However, the influence of the substitutions on the dNTP Kd was dramatic, leading to a decrease in affinity of 13-fold and 52-fold respectively for K65R and K65A (Table 2). 2010 Journal of molecular biology Result HIV K65A;K65R 156;147 160;151 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. However, the positioning was not grossly altered in the K65A and K65R RT mutants compared to the wild-type (Figure 4). 2010 Journal of molecular biology Result HIV K65A;K65R 56;65 60;69 RT 70 72 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. In a comparison between matched (A:T, Table 1) and mismatched primer termini (A:G, Table 2), it can be seen that the wild-type enzyme discriminates against the mismatched primer terminus largely on the basis of a reduced kpol; however, with the K65R and K65A substitutions the effect of increased Kd for dNTP (decreased affinity) becomes an increasingly important factor in the discrimination. 2010 Journal of molecular biology Result HIV K65A;K65R 254;245 258;249 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. In order to examine the role of lysine 65 on replication fidelity, we employed recombinant, purified HIV-1 RT with either a K65R or K65A substitution, and compared them to the wild-type enzyme in fidelity assays. 2010 Journal of molecular biology Result HIV K65A;K65R 132;124 136;128 RT 107 109 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. On the G:T mismatched termini the wild type and K65R enzymes were also mostly in a -17 position; however, this effect was less pronounced with the K65A substitution. 2010 Journal of molecular biology Result HIV K65A;K65R 147;48 151;52 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Overall, the K65A mutation caused an increase in misinsertion fidelity of between 2 and 4-fold compared to the wild-type enzyme. 2010 Journal of molecular biology Result HIV K65A 13 17 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Pre-steady state kinetic measurements were used to quantify the differences in extension, and it was demonstrated that from the A:G mismatch the K65R mutant did not alter kpol, and with the K65A mutant, the reduction in kpol was modest (4.5-fold compared to wild-type). 2010 Journal of molecular biology Result HIV K65A;K65R 190;145 194;149 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Qualitative experiments showed, as previously demonstrated, that the K65A substitution resulted in an RT that was far less efficient at dNTP misinsertion than the wild-type enzyme (Figure 1), particularly in the misinsertion of dCMP and dTMP opposite a template thymine. 2010 Journal of molecular biology Result HIV K65A 69 73 RT 102 104 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Qualitatively, it was clear that both the conservative (K65R) and nonconservative (K65A) substitutions greatly reduced the efficiency of mismatch primer extension from an A:G mismatch (Figure 2), with K65A having a greater effect. 2010 Journal of molecular biology Result HIV K65A;K65A;K65R 83;201;56 87;205;60 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Selection against the pyrimidine nucleotides was mostly at the level of dNTP binding; the effect of the K65A substitution was to increase the Kd of the incorrect dNTP (for dCTP, the Kd was increased 166-fold for wild type and 515-fold in K65A compared to the correct dNTP), with only a minor effect on kpol relative to the wild-type (Table 1). 2010 Journal of molecular biology Result HIV K65A;K65A 104;238 108;242 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The fold change in kpol from correct dNTP insertion for WT was 67-fold and for K65A, it was 132-fold whilst the Kd fold change from correct dNTP was similar for the two enzymes (83-fold and 104-fold for wild-type and K65A respectively, see Table 1). 2010 Journal of molecular biology Result HIV K65A;K65A 79;217 83;221 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The K65R substitution had a less defined effect on misinsertion fidelity. 2010 Journal of molecular biology Result HIV K65R 4 8 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The nucleotide Kd was also increased for the K65A enzyme, but to a much more modest extent (2.5-fold compared to wild-type). 2010 Journal of molecular biology Result HIV K65A 45 49 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Utilizing a template purine, a greater fold-reduction in catalytic efficiency (kpol/Kd) was observed for misinsertion of the pyrimidine nucleotides (dCMP and TMP) by K65A, as compared to misinsertion of dGMP (Table 1). 2010 Journal of molecular biology Result HIV K65A 166 170 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Although limiting dilution sequencing did not detect K65R, it did detect each of the other 33 nucleotide and three amino acid mutations that were present in more than 1.0% of UDPS reads in these two samples. 2010 PloS one Result HIV K65R 53 57 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Among the subtype B samples, K65R was detected in more than 1.0% of reads in a sample with a complex mixture of KKK nucleotide variants including AAA-AAG-AAA (the second-most common subtype C pattern) in 38% of reads, AAG-AAA-AAA (the most common subtype B pattern) in 7% of reads, and an uncommon pattern AAG-AAG-AAA in 50% of reads. 2010 PloS one Result HIV K65R 29 33 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Among the subtype C samples, K65R was detected in at least 1.0% of reads in eight samples, including 7 of 11 with the most common subtype C pattern and the one sample with the second-most common subtype C pattern. 2010 PloS one Result HIV K65R 29 33 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Clonal analysis of two subtype C viruses for which more than 2.0% of UPDS reads contained K65R. 2010 PloS one Result HIV K65R 90 94 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Despite the fact that the K65R reads in this subtype B sample (1.1% of all reads) were encoded by AAA-AGA-AAA, there were no reads with the closest wildtype variant, AAA-AAA-AAA. 2010 PloS one Result HIV K65R 26 30 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Figure 1 shows that UDPS detected K65R in a higher proportion of sequence reads of subtype C plasma samples than in subtype B plasma samples (1.04% vs. 2010 PloS one Result HIV K65R;K65R 35;34 39;38 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. For eight of the 16 repeated subtype C samples, the proportion of reads with K65R was >1.0% in each of the duplicate runs and for seven of the 16 repeated subtype C samples, the proportion of reads with K65R was <1.0% on both runs. 2010 PloS one Result HIV K65R;K65R 77;203 81;207 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. For plasmid clones with a subtype C nucleotide pattern, UDPS detected K65R in a mean 1.1% of reads (range 0.7-1.3). 2010 PloS one Result HIV K65R 70 74 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. In contrast, for plasmid clones with a subtype B nucleotide pattern, UDPS detected K65R in a mean of 0.2% reads (range 0.1-0.3). 2010 PloS one Result HIV K65R 83 87 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. In contrast, the four clones with the two most common subtype B KKK patterns had K65R in a median of 0.15% of reads (range 0.1%-0.3%; P = 0.007; Wilcoxan Rank Sum Test). 2010 PloS one Result HIV K65R 81 85 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. K65R was detected in at least 1.0% of reads in 8/18 (44%) subtype C samples and in 1/27 (3.7%) subtype B samples (p = 0.01; Fisher's Exact Test). 2010 PloS one Result HIV K65R 0 4 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Of the four subtype C samples with the most commonly reported subtype B KKK nucleotide variant (AAG-AAA-AAA), none had K65R in 1.0% or more of reads. 2010 PloS one Result HIV K65R 119 123 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Similarly, although 57 of 3613 UDPS reads of sample 9635 had K65R, none of the 254 limiting dilution clones we sequenced of this sample had the mutation (p = 0.02, Fisher's Exact Test). 2010 PloS one Result HIV K65R 61 65 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Table 2 shows the dominant wildtype KKK nucleotide patterns in the UDPS reads of the 18 subtype C and 27 subtype B viruses and the KRK nucleotide patterns for those samples in which K65R was present in at least 1.0% of UDPS reads. 2010 PloS one Result HIV K65R;K65R 183;182 187;186 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Table 3 shows that, although 133 of 5186 UDPS reads of sample SCR268 had K65R, none of 265 limiting dilution clones of the same sample had the mutation (p = 0.001; Fisher's Exact Test). 2010 PloS one Result HIV K65R 73 77 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Table 4 shows that a median of 1.2% of 454 UDPS reads (range: 0.7%-1.3%) of the eight clones with the two most common subtype C KKK patterns had K65R. 2010 PloS one Result HIV K65R;K65R 146;145 150;149 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Taken together, the limiting dilution and molecular cloning sequencing results strongly suggest that PCR error was responsible for the subsequent frequent false positive detection of K65R by UDPS of subtype C samples. 2010 PloS one Result HIV K65R 183 187 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The median proportion of reads with K65R was similar in the forward (0.93%) and reverse (1.2%) UDPS reads. 2010 PloS one Result HIV K65R 36 40 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The proportion of K65R clones was 16-fold to 80-fold lower in the samples amplified using PfuUltra II Fusion than in the samples amplified with Taq/Pwo (Table 4 footnote). 2010 PloS one Result HIV K65R 18 22 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The proportion of UDPS reads containing K65R appeared to be entirely dependant on the KKK pattern in the sample. 2010 PloS one Result HIV K65R 40 44 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The subtype from which the surrounding viral sequence was derived did not significantly influence the number of reads with K65R. 2010 PloS one Result HIV K65R 123 127 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. To determine whether the high frequency of K65R reads in subtype C viruses reflected a natural occurrence of this mutation at low levels in subtype-C-infected individuals or a technical artifact of either PCR or UDPS, we performed clonal dideoxynucleotide sequencing on the two subtype C viruses with the highest proportions of K65R reads. 2010 PloS one Result HIV K65R;K65R 43;328 47;332 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Viruses with the wildtype KKK motif were obtained from NRTI-naive individuals and viruses with the K65R mutation from NRTI-treated individuals. 2010 PloS one Result HIV K65R 99 103 NRTI;NRTI 55;118 59;122 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. For the ACT double mutant V82T, I84V, the relative binding free energy was also calculated by the more rigorous and computationally more intensive thermodynamic integration method. 2010 Journal of chemical theory and computation Result HIV I84V;V82T 32;26 36;30 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. Overall there was a decrease in the vdW interaction energy between the protease and DRV, mostly on the 4- amino phenyl side, as the volume of the binding pocket was effectively enlarged as the mutations within the active site were to smaller residues (V82A in Flap+ and I84V in ACT). 2010 Journal of chemical theory and computation Result HIV I84V;V82A 270;252 274;257 PR 71 79 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. As described above, T242X had a high reversion rate. 2010 PloS one Result HIV T242X 20 25 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. At the K76X site restricted by A*02, the mutation rate was calculated as 3/3 ( = 1.0), three K76K-A*02-positive contact cases divided by three K76R-A*02-negative index cases. 2010 PloS one Result HIV K76K;K76R;K76X 93;143;7 97;147;11 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Both had very high CD4 cell counts of >500 cell/microL and very low viral loads of less than 104 copies/mL, which is in distinct contrast to the remaining six B*57/*58-negative spouses who lacked T242N (median plasma viral load, 5.39 log copies/mL), and supports the results of the recent study by Chopera et al. 2010 PloS one Result HIV T242N 196 201 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Conversely, F79X (A*24), K76X (A*02), and T242X (B*58) had mutation rates of 1.00 and the former two had low reversion rates. 2010 PloS one Result HIV F79X;K76X;T242X 12;25;42 16;29;47 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Five of the 23 B*57/*58-positive subjects did not carry T242X, and there was no statistically significant difference in their plasma viral loads or CD4 cell counts, i.e., in terms of the presence or absence of T242X in these patients (data not shown). 2010 PloS one Result HIV T242X;T242X 56;210 61;215 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. For instance, at the S9X site restricted by B*13, which was selected by non-dominant amino acid, the mutation rate was calculated as 5/11 ( = 0.45), five S9T-B*13-positive contact cases divided by 11 S9S-B*13-negative index cases. 2010 PloS one Result HIV S9T;S9X 154;21 157;24 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. However, because the T242N escape mutation is known to emerge within the first three months of infection in B*57-positive subjects, it is unlikely that these six contact cases had acquired the wild-type T242 virus, but instead, the transmitted T242N probably reverted after its transmission to these recipients. 2010 PloS one Result HIV T242N;T242N 21;244 26;249 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. However, the roles of T242N and the compensatory mutations in CRF01_AE infections are unknown. 2010 PloS one Result HIV T242N 22 27 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Interestingly, T242X (B*58) was outstanding in that both its mutation rate and reversion rate were very high. 2010 PloS one Result HIV T242X 15 20 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. It was recently reported that the transmission of viruses with attenuating CTL escape mutations, particularly T242N from B*57-restricted CTL, is associated with better early clinical outcomes in HLA-unmatched recipients. 2010 PloS one Result HIV T242N 110 115 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Its reversion rate was calculated as 4/6 ( = 0.67), four S9S-B*13-negative contact cases divided by six S9T-B*13-positive index cases (see supplementary data for details of the mutation and reversion sequence variations, Table S2). 2010 PloS one Result HIV S9S;S9T 57;104 60;107 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Moreover, several mutations within the cyclophilin A binding loop, such as H219 and M228, have been shown to compensate to some extent for the reduced viral replicative capacity caused by T242N. 2010 PloS one Result HIV T242N 188 193 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Only two B*57/*58-negative spouses carried the T242N mutation at the time of sampling. 2010 PloS one Result HIV T242N 47 52 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. P255X (A*11) and I223X (B*13) scored reversion rates of 1.00 and both had low mutation rates. 2010 PloS one Result HIV I223X;P255X 17;0 22;5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Several studies have demonstrated that the T242N substitution affects viral replicative fitness in vitro and it is believed to contribute to the protective effect of these alleles against the progression of HIV disease. 2010 PloS one Result HIV T242N 43 48 HIV diseases 207 218 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Some HLA-associated amino acid variations were located at anchor positions of binding peptides: A*24-associated F79X, B*40-associated E93X, and B*58-associated V485X (Table 1). 2010 PloS one Result HIV E93X;F79X;V485X 134;112;160 138;116;165 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T242N mutations and transmission. 2010 PloS one Result HIV T242N 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. The reversion rate was calculated as 1/13 ( = 0.077), one K76R-A*02-negative contact case divided by 13 K76K-A*02-positive index cases. 2010 PloS one Result HIV K76R;K76K 58;104 62;108 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. The vast majority of T242X mutations were T242N, known as an escape mutation from CTL (TSTLQEQIGW: TW10), restricted by the protective HLA alleles B*57 and B*5801 in the setting of clade B and C infections. 2010 PloS one Result HIV T242N;T242X 42;21 47;26 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. We identified three other patients without the B*57/B*58 alleles who carried viruses with T242N, and they all had very low viral loads of less than 104 copies/mL (data not shown). 2010 PloS one Result HIV T242N 90 95 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. We then stratified the B57*/*58-positive patients with T242X according to the presence/absence of the described compensatory mutations. 2010 PloS one Result HIV T242X 55 60 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. The most frequent RT mutations were M184V (n = 11), conferring resistance to lamivudine and emtricitabine, and Y181C (n = 4), G190A/S (n = 4) and K103N (n = 4), conferring resistance to NNRTIs. 2010 The Journal of antimicrobial chemotherapy Result HIV G190A;G190S;K103N;M184V;Y181C 126;126;146;36;111 133;133;151;41;116 NNRTI;RT 186;18 192;20 20578491 Virologic and immunologic outcomes in HIV-infected Cambodian children after 18 months of highly active antiretroviral therapy (HAART). However, mutations associated with resistance to lamivudine (M184V) and to non-nucleoside reverse transcriptase inhibitors (Y181C and G190A) were detected in samples collected from both children at 18 months. 2010 The Southeast Asian journal of tropical medicine and public health Result HIV G190A;M184V;Y181C 134;61;124 139;66;130 NNRTI 75 111 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. 2j, lane 3) and A42C/T54C (lane 9) had enriched 6-mer bands, indicating that these cysteine pairs were within favorable disulfide bonding distance. 2010 Journal of molecular biology Result HIV A42C;T54C 16;21 20;25 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. A series of follow-up experiments showed that: (1) the in vitro crosslinking efficiency of A14C/E45C could be driven essentially to completion by performing the assembly reactions in stoichiometric amounts of betaME (data not shown; but see. 2010 Journal of molecular biology Result HIV A14C;E45C 91;96 95;100 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. A14C/E45C crosslinked with at least 90% efficiency and was therefore selected for further analysis (see below). 2010 Journal of molecular biology Result HIV E45C;A14C 5;0 9;4 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Addition of dimer interface mutations to A14C/E45C gave soluble hexamers. 2010 Journal of molecular biology Result HIV A14C;E45C 41;46 45;50 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Although the N21C/A22C spheres lacked strict icosahedral symmetry, this result supports the finding that retroviral CA hexamers and pentamers are quasi-equivalent, i.e., the same (or overlapping) protein surfaces are used to create both capsomers. 2010 Journal of molecular biology Result HIV A22C;N21C 18;13 22;17 Capsid 116 118 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. As expected, the negative control, Q13C/E45C, migrated as a single band corresponding to the non-crosslinked monomer, consistent with the prediction based on the cryoEM model. 2010 Journal of molecular biology Result HIV E45C;Q13C 40;35 44;39 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. As for the CC1 construct, soluble A42C/T54C assemblies were obtained by the addition of the W184A and M185A mutations to the CTD; the A42C/T54C/W184A/M185A construct is hereinafter referred to as CC2. 2010 Journal of molecular biology Result HIV A42C;M185A;T54C;W184A;A42C;M185A;T54C;W184A 134;150;139;144;34;102;39;92 138;155;143;149;38;107;43;97 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Because the CTD-CTD interface does not directly stabilize the hexamer, the W184A and M185A mutations were not expected to affect formation of the crosslinked A14C/E45C hexamers. 2010 Journal of molecular biology Result HIV A14C;E45C;M185A;W184A 158;163;85;75 162;167;90;80 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Characterization of CA A14C/E45C hexamers. 2010 Journal of molecular biology Result HIV A14C;E45C 23;28 27;32 Capsid 20 22 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Four mutants assembled into tubes that appeared similar in morphology to the wildtype tubes (Q13C/E45C. 2010 Journal of molecular biology Result HIV E45C;Q13C 98;93 102;97 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. In contrast to the wildtype background, addition of these mutations to A14C/E45C produced constructs that remained competent for assembly. 2010 Journal of molecular biology Result HIV A14C;E45C 71;76 75;80 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Many of these assemblies were single-layered (data not shown), suggesting that the W184A mutation may have altered the native curvature of the hexameric lattice, by changing the packing geometry at the dimerization interface. 2010 Journal of molecular biology Result HIV W184A 83 88 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Note that these constructs contain mutations at or near Arg18 (Fig.1a and Table 1), and therefore the highly curved and closed particles presumably arose by the incorporation of pentamers into the assembling hexagonal lattices, in analogy to the R18A and R18L mutants. 2010 Journal of molecular biology Result HIV R18A;R18L 246;255 250;259 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Of the constructs that assembled into wildtype-like tubes, A14C/E45C. 2010 Journal of molecular biology Result HIV A14C;E45C 59;64 63;68 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Structure of crosslinked HIV-1 CA A14C/E45C/W184A/M185A (CC1) 2010 Journal of molecular biology Result HIV A14C;E45C;M185A;W184A 34;39;50;44 38;43;55;49 Capsid 31 33 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Structure of crosslinked HIV-1 CA A14C/E45C/W184A/M185A (CC1). 2010 Journal of molecular biology Result HIV A14C;E45C;M185A;W184A 34;39;50;44 38;43;55;49 Capsid 31 33 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Structure of crosslinked HIV-1 CA A42C/T54C/W184A/M185A (CC2) 2010 Journal of molecular biology Result HIV A42C;M185A;T54C;W184A 34;50;39;44 38;55;43;49 Capsid 31 33 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Structure of crosslinked HIV-1 CA A42C/T54C/W184A/M185A (CC2). 2010 Journal of molecular biology Result HIV A42C;M185A;T54C;W184A 34;50;39;44 38;55;43;49 Capsid 31 33 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Taken together, these results indicated that the engineered disulfide bond stabilized the A14C/E45C hexamer both in vitro and in authentic virions, and did not disrupt the native architecture or surface properties of the hexameric capsid lattice. 2010 Journal of molecular biology Result HIV A14C;E45C 90;95 94;99 Capsid 231 237 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. The A14C/E45C construct also assembled readily even at low nanomolar concentrations (data not shown). 2010 Journal of molecular biology Result HIV A14C;E45C 4;9 8;13 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. The A14C/E45C/M185A mutant was prone to aggregation (but also assembled; data not shown) and was therefore not analyzed further. 2010 Journal of molecular biology Result HIV A14C;E45C;M185A 4;9;14 8;13;19 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. The A14C/E45C/W184A construct assembled into mixtures of tubes and flat sheets, which crosslinked into 6-mers with ~100% efficiency (data not shown). 2010 Journal of molecular biology Result HIV A14C;E45C;W184A 4;9;14 8;13;19 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. The A14C/E45C/W184A/M185A construct (hereinafter referred to as CC1) also formed tubes. 2010 Journal of molecular biology Result HIV A14C;E45C;M185A;W184A 4;9;20;14 8;13;25;19 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. The N21C/A22C construct was a notable outlier: its SDS-PAGE profile showed an enriched 5-mer band, with essentially no 6-mer band. 2010 Journal of molecular biology Result HIV A22C;N21C 9;4 13;8 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. The remainder of the constructs formed highly curved particles (i.e., spheres, small rods, cones, and spirals) similar to the previously described R18A and R18L HIV-1 CA mutants. 2010 Journal of molecular biology Result HIV R18A;R18L 147;156 151;160 Capsid 167 169 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Thus, it was not possible to disassemble the crosslinked tubes and crystallize the A14C/E45C hexamers. 2010 Journal of molecular biology Result HIV A14C;E45C 83;88 87;92 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. To obtain discrete, soluble A14C/E45C hexamers for crystallization, we disrupted the CTD-CTD linkages by introducing the W184A and M185A mutations into helix 9, thereby preventing further polymerization of the crosslinked hexamers into tubes or other capsid-like particles. 2010 Journal of molecular biology Result HIV A14C;E45C;M185A;W184A 28;33;131;121 32;37;136;126 Capsid 251 257 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. Tubes composed of crosslinked CA A14C/E45C were hyperstable. 2010 Journal of molecular biology Result HIV A14C;E45C 33;38 37;42 Capsid 30 32 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. We first focused on the A14C/E45C construct, because it assembled into wildtype-like tubes and crosslinked efficiently into 6-mers. 2010 Journal of molecular biology Result HIV A14C;E45C 24;29 28;33 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. We speculate that within the N21C/A22C particles, the engineered cysteines may be partly oxidized in the hexamers and completely oxidized in the pentamers. 2010 Journal of molecular biology Result HIV A22C;N21C 34;29 38;33 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. We tested the W184A and M185A mutations singly and in combination. 2010 Journal of molecular biology Result HIV M185A;W184A 24;14 29;19 20600115 Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. We therefore revisited the A42C/T54C mutant for further analysis: this construct displayed a ladder of 1 to 6-mers on SDS-PAGE. 2010 Journal of molecular biology Result HIV A42C;T54C 27;32 31;36 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. A G116E substitution affects viral sensitivity to CM TRIM5alpha-mediated restriction in a single-round infection assay. 2010 Retrovirology Result HIV G116E 2 7 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. As expected, the lentivector with the G116E substitution showed reduced suppression by CM TRIM5alpha compared with the wild type CA (Figures 5C and 5D). 2010 Retrovirology Result HIV G116E 38 43 Capsid 129 131 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Because the replicative capability of NL-4/5S6/7SvifS in human cells was lower than that of the wild type virus as described above, it was highly likely that the infectivity of 4/5S6/7S-GFP would also be lower than those of WT-GFP and G116E-GFP. 2010 Retrovirology Result HIV G116E 235 240 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Consistent with the results that NL-G116E could replicate in human cells expressing CM TRIM5alpha (Figure 4B), the GFP-expressing virus with the G116E substitution was more resistant to CM TRIM5alpha-mediated restriction than the wild type virus, while both viruses were completely restricted by Rh TRIM5alpha (Figure 5A, Figure 5B left). 2010 Retrovirology Result HIV G116E;G116E 36;145 41;150 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Furthermore, when we used TRIM5alpha knockout Jurkat cells, we also failed to detect the difference in sensitivity to human TRIM5alpha between the wild type and G116E virus (data not shown). 2010 Retrovirology Result HIV G116E 161 166 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. In particular, the virus with SIVmac L4/5 and L6/7 tended to contain increased amount of p55 Gag precursors (lane 6, bottom); however, addition of G116E substitution did not facilitate the cleavage of Gag (lane 7). 2010 Retrovirology Result HIV G116E 147 152 Gag;Gag 93;201 96;204 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. In the case of TK-ts13, cells stably expressing human TRIM5alpha in which TRIM5alpha expression is in more physiological levels; however, the difference in sensitivity to human TRIM5alpha between the wild type and G116E lentivector was not observed (Figure 5C and 5D). 2010 Retrovirology Result HIV G116E 214 219 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Notably, the loops being flexible parts of the protein are slightly repositioned in the modeled structure with G116E substitution (Figure 7A and 7B). 2010 Retrovirology Result HIV G116E 111 116 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Nucleotide sequence analysis of the resultant clones revealed that 6 out of 6 independent clones carried a single nucleotide substitution at the 347th position of the CA region, resulting in a G-to-E substitution at the 116th position of the CA (G116E). 2010 Retrovirology Result HIV G116E 246 251 Capsid;Capsid 167;242 169;244 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. On the contrary, the GFP-expressing virus with G116E was more sensitive to humanTRIM5alpha expressed from the SeV in CEMss cells than the wild type virus (Figure 5B, right). 2010 Retrovirology Result HIV G116E 47 52 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The fragment of NL-G116E, NL-4/5S6/7SvifS, or NL-4/5SG116E6/7SvifS corresponding to the MA and CA was transferred to an env-deleted HIV-1 genomic clone, which express GFP after infection. 2010 Retrovirology Result HIV G116E 19 24 Env;Matrix;Capsid 120;88;95 123;90;97 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The growth of the NL4-3 virus was not affected by human TRIM5alpha, while that of NL-G116E was slightly suppressed by human TRIM5alpha. 2010 Retrovirology Result HIV G116E 85 90 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Therefore, we used higher input doses of 4/5S6/7S-GFP and 4/5SG116E6/7S-GFP than those of WT-GFP and G116E-GFP. 2010 Retrovirology Result HIV G116E 101 106 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. These data suggest that the rescued replicative capability of NL-4/5S6/7SvifSd42 in human cells (Figure 2) was the result, at least partly, of the acquisition of the G116E substitution in the CA. 2010 Retrovirology Result HIV G116E 166 171 Capsid 192 194 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. These results in the single-round infection assay clearly confirmed our results in the live virus replication experiments showing that the G116E substitution conferred resistance against CM-TRIM5alpha-mediated restriction. 2010 Retrovirology Result HIV G116E 139 144 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. These results indicated that the effect of G116E substitution is virtually negligible at physiological levels of endogenous human TRIM5alpha, although this substitution increases the susceptibility of HIV-1 to human TRIM5alpha. 2010 Retrovirology Result HIV G116E 43 48 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. These results suggest that the viruses with G116E substitution were more sensitive to human TRIM5alpha although the G116E substitution occurred during long-term cultivation of human cells infected with NL-4/5S6/7SvifS. 2010 Retrovirology Result HIV G116E;G116E 44;116 49;121 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. To clarify the impact of the single G-to-E substitution in CA on virus growth in the presence of CM TRIM5alpha, we next introduced a G116E substitution in NL-vifS to generate NL-G116EvifS. 2010 Retrovirology Result HIV G116E 133 138 Vif;Capsid 158;59 161;61 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. To determine whether the single amino acid substitution at the 116th position of the CA improved the replicative capability of NL-4/5S6/7SvifS in human cells, we introduced the G116E mutation into NL-4/5S6/7SvifS. 2010 Retrovirology Result HIV G116E 177 182 Capsid 85 87 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. To examine the effect of G116E substitution in cells with more physiological levels of TRIM5alpha expression, we established TK-ts13 hamster cells stably expressing CM or human TRIM5alpha and inoculated lentivector expressing GFP under the cytomegalovirus promoter into these cells. 2010 Retrovirology Result HIV G116E 25 30 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. To exclude any possible effect of SIVmac vif in NL-G116EvifS on TRIM5alpha-mediated restriction, we constructed NL-G116E, a virus with a single amino acid substitution at the 116th position of the CA only (Figure 4B). 2010 Retrovirology Result HIV G116E;G116E 115;51 120;56 Vif;Capsid 41;197 44;199 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. While both the GFP-expressing viruses with the 4/5S6/7S (4/5S6/7S-GFP and 4/5SG116E6/7S-GFP) were resistant to CM TRIM5alpha, an additional effect of the G116E substitution was not observed (Figure 5B, left). 2010 Retrovirology Result HIV G116E 154 159 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. All patients developed the M184V mutation, four patients developed T215Y and three developed L210W. 2010 PloS one Result HIV L210W;M184V;T215Y 93;27;67 98;32;72 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. At this time, the M184I mutation had increased from 0.08% to 0.27% in patient 2 and from 0.08% to 63% in patient 5. 2010 PloS one Result HIV M184I 18 23 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Finally, none of the 10 most common variants during treatment interruption had the M184V mutation, which was present in multiple variants during treatment failure. 2010 PloS one Result HIV M184V 83 88 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. However, after prolonged treatment interruption the prevalence of the resistance mutations rapidly decreased and after five month the M184V mutation was undetectable and the T215Y present at 0.10% (Table 5). 2010 PloS one Result HIV M184V;T215Y 134;174 139;179 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. However, during prolonged 3TC containing treatment the M184V variants were completely replaced by the M184V-T215Y variants, suggesting that the M184V-T215Y variants were more fit during selection pressure from 3TC, d4T and ddI. 2010 PloS one Result HIV M184V;M184V;M184V;T215Y;T215Y 55;102;144;108;150 60;107;149;113;155 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. However, it should be noted that M184V was observed, but the levels of this mutation were not above the statistically derived cut-off value, because the error rate was comparably high for this mutation (median cut-off value 0.17%) (Table 2). 2010 PloS one Result HIV M184V 33 38 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. However, the M184I mutation was completely replaced by M184V after 8 months of 3TC treatment in patient 2 and 3 years in patient 5. 2010 PloS one Result HIV M184I;M184V 13;55 18;60 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. However, the rate of decay of M184V varied and after 3-8 months the mutation was not detectable in virus from plasma. 2010 PloS one Result HIV M184V 30 35 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In contrast, patient 2 and 4 had undetectable levels of M184V already 3 and 6 months after 3TC interruption, respectively (Table 5). 2010 PloS one Result HIV M184V 56 61 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In patient 1 and 4 low frequencies of M184V were found 1 and 3 months after treatment interruption, respectively, representing 2.3% and 3.9% (Table 5). 2010 PloS one Result HIV M184V 38 43 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In patient 6 the level of resistance was still high 2 weeks after treatment interruption when M184V and T215Y was found in 98.5% and 99.3% of the quasispecies, respectively (Table 5. 2010 PloS one Result HIV M184V;T215Y 94;104 99;109 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In the remaining two patients who developed the T215Y mutation (patients 5 and 6), no gradual increase was observed and a prevalence of 99.9% was seen after 5 to 13 months of treatment. 2010 PloS one Result HIV T215Y 48 53 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In the three remaining patients no detectable levels of M184I was observed in the first available sample after start of 3TC therapy, which was obtained between 9 month to 2 years (patients 1, 3 and 4) after start of therapy. 2010 PloS one Result HIV M184I 56 61 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In two of the four patients (patients 1 and 3) the T215Y mutation also increased gradually from 78 and 90.3% after approximately 16 months of AZT-containing treatment to 99.9% 12 months and 19 months later, respectively. 2010 PloS one Result HIV T215Y 51 56 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Instead, in these patients the M184V mutation dominated and was found in 99.5-99.9% of the virus population (Table 4). 2010 PloS one Result HIV M184V 31 36 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. It is interesting to note that several different M184V-T215Y variants co-existed, suggesting that they did not all arise through recombination but by convergent selection on these sites. 2010 PloS one Result HIV M184V;T215Y 49;55 54;60 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Nine months after 3TC introduction variants that only had the M184V mutation co-existed with variants with linked M184V and T215Y mutations. 2010 PloS one Result HIV M184V;M184V;T215Y 62;114;124 67;119;129 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. No detectable pre-existence of the M184V, T215Y/F and NNRTI resistance mutations. 2010 PloS one Result HIV M184V;T215F;T215Y 35;42;42 40;49;49 NNRTI 54 59 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. None of the five individuals had significant levels of Y181C/I/V, M184V, Y188C/L/H, G190S/A, L210W, T215Y/F and K219E before treatment (Table 3). 2010 PloS one Result HIV G190A;G190S;K219E;L210W;M184V;T215F;T215Y;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 84;84;112;93;66;100;100;55;55;55;73;73;73 91;91;117;98;71;107;107;64;64;64;82;82;82 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Our results show that T215A and T215I not only evolve following treatment interruption in patients with failing therapy, but also can exist as minority variants prior to any therapy. 2010 PloS one Result HIV T215A;T215I 22;32 27;37 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Significant preexistence of the M184I, T215A and T215I mutations. 2010 PloS one Result HIV M184I;T215A;T215I 32;39;49 37;44;54 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Since this patient did not develop the T215Y/F mutations despite a failing AZT containing regimen, we cannot exclude problems with adherence. 2010 PloS one Result HIV T215F;T215Y 39;39 46;46 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. The M184I mutation confers high-level of resistance (about 1000-fold) to 3TC and during treatment failure it is known to appear transiently before being replaced by M184V. 2010 PloS one Result HIV M184I;M184V 4;165 9;170 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. The M184I resistance mutation was detected in the virus populations from four of five patients (patients 1, 2, 3, and 5) at levels that ranged from 0.07% to 0.09% (Table 3). 2010 PloS one Result HIV M184I 4 9 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. The M184V mutation increased in prevalence during failing 3TC-containing regimen in all patients and finally constituted between 99.5% and 99.9% of the viral quasispecies. 2010 PloS one Result HIV M184V 4 9 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Thus, the M184V resistance mutations decreased quickly after treatment interruption in all five patients. 2010 PloS one Result HIV M184V 10 15 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Thus, we did not detect significant pre-treatment levels of the three important NRTI resistance mutations (M184V, T215Y and T215F) nor the three important NNRTI mutations (Y181C/I/V, Y188C/L/H and G190S/A). 2010 PloS one Result HIV G190A;G190S;M184V;T215F;T215Y;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 197;197;107;124;114;172;172;172;183;183;183 204;204;112;129;119;181;181;181;192;192;192 NNRTI;NRTI 155;80 160;84 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Transient increase of M184I during treatment failure. 2010 PloS one Result HIV M184I 22 27 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. We also investigated the levels of preexisting T215 reversion mutations (T215A/C/D/E/G/H/I/L/N/S/V) and found that four of five patients had preexisting levels of T215A and/or T215I that ranged from 0.05% to 0.11% (Table 3), whereas we did not detect any of the other 215 reversion mutations. 2010 PloS one Result HIV T215A;T215A;T215C;T215D;T215E;T215G;T215H;T215I;T215I;T215L;T215N;T215S;T215V 73;163;73;73;73;73;73;73;176;73;73;73;73 98;168;98;98;98;98;98;98;181;98;98;98;98 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. By contrast, introduction of L74M into a N155H backbone further reduced viral fitness in the absence of drug, but resulted in increased fitness in the presence of drug. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV L74M;N155H 29;41 33;46 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. By contrast, the E92Q/N155H mutant was fitter than the E138K/Q148H mutant both in the absence and presence of 5.0 microM RAL (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;E92Q;N155H;Q148H 55;17;22;61 60;21;27;66 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Compared to WT, the N155H mutation conferred 19-fold resistance, and the Q148H(R) (K) mutations conferred 7- to 22-fold resistance to raltegravir. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;Q148H 20;73 25;78 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Fitness of N155H mutants. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H 11 16 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Fitness of the Q148H(R)(K) mutants. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV Q148H 15 20 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. However, the E138K/Q148H mutant was less fit than G140S/Q148H in the absence and presence of drug. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;G140S;Q148H;Q148H 13;50;19;56 18;55;24;61 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In the absence of drug, the relative fitness difference for WT versus N155H was 3.4-fold, whereas in the presence of drug the N155H mutant had a relative fitness that was 2.0-fold greater than wild-type (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;N155H 70;126 75;131 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In the presence of raltegravir, the E138K/Q148H had a 3.0-fold relative fitness advantage over the Q148H mutant. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;Q148H;Q148H 36;42;99 41;47;104 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In these experiments, the N155H recombinants were substantially less fit than WT in the absence of raltegravir and more fit than WT in presence of 5.0 microM RAL. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H 26 31 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In these experiments, the Q148H recombinant was substantially less fit than N155H both in the absence and presence of 5.0 microM RAL. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;Q148H 76;26 81;31 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In these experiments, the Q148H/G140S recombinant was substantially fitter than E92Q/N155H both in the absence and presence of raltegravir (Fig.2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E92Q;G140S;N155H;Q148H 80;32;85;26 84;37;90;31 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Introduction of E92Q or G163R into an N155H backbone resulted in a virus with greater fitness than N155H mutant both in the absence and presence of RAL. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E92Q;G163R;N155H;N155H 16;24;38;99 20;29;43;104 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Introduction of either E138K or G140S into a Q148H backbone increased viral fitness both in the absence and presence of raltegravir. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;G140S;Q148H 23;32;45 28;37;50 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Relative fitness of Q148H versus N155H mutants. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;Q148H 33;20 38;25 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Similarly the Q148K and R mutants were less fit than WT in the absence of RAL and more fit than WT in the presence of drug (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV Q148K 14 19 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Similarly, the E138K/Q148H mutant was fitter than the L74M/N155H mutant both in the absence and presence of 5.0 microM RAL (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;L74M;N155H;Q148H 15;54;59;21 20;58;64;26 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Similarly, the G140S/Q148H mutant had a relative fitness advantage of over Q148H. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV G140S;Q148H;Q148H 15;21;75 20;26;80 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The addition of secondary mutations E138K or G140S to Q148H resulted in 36- and 245-fold raltegravir resistance, respectively. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;G140S;Q148H 36;45;54 41;50;59 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The addition of secondary mutations L74M or E92Q to N155H resulted in 28- and 55-fold resistance, respectively, but addition of G163R did not result in any substantial change in raltegravir resistance. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E92Q;G163R;L74M;N155H 44;128;36;52 48;133;40;57 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The N155H mutant had a 5.7-fold relative fitness advantage over the L74M/N155H mutant in the absence of raltegravir, whereas in the presence of RAL the L74M/N155H mutant had a 2.1-fold relative fitness advantage (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV L74M;L74M;N155H;N155H;N155H 68;152;4;73;157 72;156;9;78;162 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The N155H mutant had a relative fitness advantage over the Q148H mutant of 3.4-fold in absence of raltegravir, and a 2.4-fold advantage in the presence of drug (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;Q148H 4;59 9;64 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The Q148H/G140S mutant had a relative fitness advantage of 2.9-fold over the E92Q/N155H mutant in absence of drug, and 3.9-fold in the presence of 5.0 microM raltegravir (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E92Q;G140S;N155H;Q148H 77;10;82;4 81;15;87;9 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The Q148R and Q148K mutants were fitter than the N155H mutant in absence of drug, but less fit in the presence of 5.0 microM RAL (data not shown). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;Q148K;Q148R 49;14;4 54;19;9 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The relative fitness difference for E92Q/N155H versus N155H was 2.8-fold in absence of drug, and 6.7-fold in the presence of RAL. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E92Q;N155H;N155H 36;41;54 40;46;59 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The relative fitness difference for G140S/Q148H versus E138K/Q148H was 3.7-fold in absence of drug, and 3.1-fold in the presence of RAL (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;G140S;Q148H;Q148H 55;36;42;61 60;41;47;66 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The relative fitness difference for N155H/G163R versus N155H was 3.4-fold in absence of drug, and 2.1-fold in the presence of RAL. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV G163R;N155H;N155H 42;36;55 47;41;60 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The relative fitness difference for WT versus Q148H was 13.7-fold in absence of raltegravir, whereas the mutant had a 1.8-fold relative fitness advantage over WT in the presence of drug (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV Q148H 46 51 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The relative replicative fitness of Q148H(R)(K) mutants was compared to WT in growth competitions assays. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV Q148H 36 41 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The relative replicative fitness of recombinant viruses carrying the N155H mutation was compared to WT in growth competitions assays. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H 69 74 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. To determine how the secondary RAL resistance mutations L74M, E92Q and G163R affect the fitness of N155H mutants, we compared the relative replicative fitness of the N155H mutants to that of the L74M/N155H, E92Q/N155H or N155H/G163R double mutants. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E92Q;E92Q;G163R;G163R;L74M;L74M;N155H;N155H;N155H;N155H;N155H 62;207;71;227;56;195;99;166;200;212;221 66;211;76;232;60;199;104;171;205;217;226 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. To determine the effect of the secondary raltegravir resistance mutations E138K and G140S on the fitness of the Q148H mutant, we compared the relative replicative fitness of the Q148H mutant to that of double mutants E138K/Q148H and G140S/Q148H. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;E138K;G140S;G140S;Q148H;Q148H;Q148H;Q148H 74;217;84;233;112;178;223;239 79;222;89;238;117;183;228;244 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. To help understand why the N155H mutant usually emerges before the Q148H mutant, we compared the relative replicative fitness of recombinant viruses carrying the Q148H and N155H mutations in growth competitions assays. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;N155H;Q148H;Q148H 27;172;67;162 32;177;72;167 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. We then compared the fitness of various Q148H and N155H double-mutants to each other in pair-wise growth competition assays. 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV N155H;Q148H 50;40 55;45 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. When competed against each other in the presence of raltegravir, the N155H/G163R mutant showed 2.1-fold greater fitness than the L74M/N155H mutant and the E92Q/N155H mutant in turn had a 3.7-fold relative fitness advantage over the N155H/G163R mutant (Table 2). 2010 Journal of acquired immune deficiency syndromes (1999) Result HIV E92Q;G163R;G163R;L74M;N155H;N155H;N155H;N155H 155;75;238;129;69;134;160;232 159;80;243;133;74;139;165;237 20649426 Effect of acyclovir on HIV-1 set point among herpes simplex virus type 2-seropositive persons during early HIV-1 infection. None of the samples had mutations at the following positions in HIV-1 reverse transcriptase that have been associated with acyclovir selection in vitro: V75I, T69N, W71X, R72X, Q151M, and M184V. 2010 The Journal of infectious diseases Result HIV M184V;Q151M;R72X;T69N;V75I;W71X 188;177;171;159;153;165 193;182;175;163;157;169 RT 70 91 20655872 Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. Interestingly, the A18H mutation converts Vpu to a highly selective proton channel that has amantadine sensitivity and also doubles the number of hydrophilic residues facing the pore. 2011 Biochimica et biophysica acta Result HIV A18H 19 23 Vpu 42 45 20655872 Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. The A18H mutation converts Vpu from a non-selective channel to a highly selective H+ channel that is sensitive to rimantadine. 2011 Biochimica et biophysica acta Result HIV A18H 4 8 Vpu 27 30 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. A lower resolution (2.6 A) crystal structure has been reported for the SQV complex with the double mutant PRG48V/L90M, in which Met90 showed interactions similar to those seen in the structure of PRL90M-APV. 2010 The FEBS journal Result HIV L90M;L90M 113;198 117;202 PR;PR 106;196 108;198 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. In contrast to PRI54M, mutation I54V substitutes the shorter Val in PRI54V. 2010 The FEBS journal Result HIV I54V 32 36 PR;PR 15;68 17;70 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Mutation I50V is associated strongly with resistance to APV, but not to SQV. 2010 The FEBS journal Result HIV I50V 9 13 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Mutation I54M introduces a longer side chain, and the nearby main chain atoms have shifted relative to their positions in the wild type PR. 2010 The FEBS journal Result HIV I54M 9 13 PR 136 138 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Mutation of Leu90 to Met substituted a longer side chain and introduced new van der Waals contacts with residues Asp25-Thr26. 2010 The FEBS journal Result HIV L90M 12 24 Asp 113 116 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Mutation of Thr80 to Val80, which eliminates the C-H O interaction with Ile50 Cdelta1, significantly reduces the catalytic activity and binding affinity of SQV. 2010 The FEBS journal Result HIV T80V 12 26 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Overall, the Ile54 to Met mutation improved contacts within the hydrophobic cluster, although the interatomic distances to residues 79-80/79'-80' were increased. 2010 The FEBS journal Result HIV I54M 13 25 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. The mutation I54V decreased the hydrophobic interactions within the flaps and with Pro79, however, PRI54V showed similar Ki value and only 3-fold reduced activity relative to the wild type enzyme. 2010 The FEBS journal Result HIV I54V 13 17 PR 99 101 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. 4D), and were transduced with the M184I (+) and (-) cPPT vectors. 2010 Virology Result HIV M184I 34 39 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. As seen in Figure 4B, the M184I (+) cPPT vector exhibited a high resistance to 3TC, and only a minimal decrease in transduction was seen with this vector even at 750 microM 3TC. 2010 Virology Result HIV M184I 26 31 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. As seen in Figure 5B, upon dC treatment, the M184I (-) cPPT vector gained a strong resistance to 3TC. 2010 Virology Result HIV M184I 45 50 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. As shown in Figure 2A, the M184I mutant vector showed ~70% transduction efficiency in dividing HLFs, which is only slightly reduced when compared to WT (~80%, Figure 1B). 2010 Virology Result HIV M184I 27 32 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. As shown in Figure 2B and 2C, a drastic decrease in the 2LTR copy number in the M184I (-) cPPT vector was observed, compared to the M184I (+) cPPT vector in nondividing HLFs, while the copy number of the late product synthesized from the 3' PPT was not affected by the cPPT deletion. 2010 Virology Result HIV M184I;M184I 80;132 85;137 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. As shown in Figure 4A, HLFs treated with 500microM 3TC, which is ~300 times higher than the previously published IC50 values of the WT RT HIV-1, still maintained efficient transduction levels with the M184I (+) cPPT vector, confirming the high 3TC resistance of the M184I RT. 2010 Virology Result HIV M184I;M184I 201;266 206;271 RT;RT 135;272 137;274 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. As shown in Figure 5A, both M184I (+) and (-) cPPT vectors displayed strong 3TC resistance, and thus the 3TC sensitization activity of the cPPT mutation could be effectively eliminated by the 1mM dN treatment (Figure 5A). 2010 Virology Result HIV M184I 28 33 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Basically, the M184I (-) cPPT vector almost failed to transduce nondividing HLF (<2%), supporting that the cPPT inactivation and M184I RT mutation additively reduced the vector transduction in nondividing HLFs. 2010 Virology Result HIV M184I;M184I 15;129 20;134 RT 135 137 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Briefly, these hybrid vectors were prepared by transfecting 293FT cells with varying ratios of WT to M184I RT packaging plasmids, and used to transduce serum-starved HLFs. 2010 Virology Result HIV M184I 101 106 RT 107 109 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Dividing HLFs were pre-treated with varying concentrations of 3TC, and these cells were transduced with an equal p24 level of the (+) and (-) cPPT M184I vectors. 2010 Virology Result HIV M184I 147 152 p24 113 116 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Effect of specific cellular dNTP pool changes on the 3TC sensitization property of the M184I (-) cPPT vector. 2010 Virology Result HIV M184I 87 92 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. First, we characterized the transduction of the M184I HIV-1 with respect to cell division, cellular dNTP concentration and inactivation of the cPPT primer. 2010 Virology Result HIV M184I 48 53 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. First, we measured the 3TC sensitivity of the M184I (+) and (-) vectors in the HLFs with elevated pools of all four dNTPs. 2010 Virology Result HIV M184I 46 51 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. For this test, we treated HLFs with 1mM dC alone or a mixture of dG, dT and dA, and measured the 3TC sensitivity of the M184I (-) cPPT. 2010 Virology Result HIV M184I 120 125 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. However, the reduced activity of M184I RT was rescued by increasing the dNTP concentration. 2010 Virology Result HIV M184I 33 38 RT 39 41 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. However, when the cellular dNTP pools were elevated by the dN treatment (Figure 2A), both (+) and (-) cPPT M184I vector significantly gained transduction efficiency, supporting that the dNTP concentration increase can at least partially compensate for both M184I and cPPT mutations. 2010 Virology Result HIV M184I;M184I 107;257 112;262 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Importantly, we have previously reported that the M184I RT displays a significantly reduced dNTP binding affinity when compared to the wild type (WT) RT. 2010 Virology Result HIV M184I 50 55 RT;RT 56;150 58;152 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. In contrast, a large transduction decrease was clearly observed at 500 microM of 3TC in the M184I (-) cPPT vector, suggesting that the cPPT inactivation counteracts the strong 3TC resistance of the M184I RT mutation. 2010 Virology Result HIV M184I;M184I 92;198 97;203 RT 204 206 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. In contrast, the M184I (-) cPPT vector displayed a significant decrease in its resistance to 3TC. 2010 Virology Result HIV M184I 17 22 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. In contrast, when increasing the remaining other three dNTPs, the M184I (-) cPPT vector remained sensitive to 3TC, demonstrating that a high concentration of only cellular dCTP abolishes the 3TC sensitivity of the M184I vector gained by the cPPT inactivation. 2010 Virology Result HIV M184I;M184I 66;214 71;219 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. In nondividing cells, the cPPT mutation in the M184I vector caused a 3-fold further decrease in transduction (Figure 2A), while the WT RT vector showed a 7.7-fold decrease (Figure 1B). 2010 Virology Result HIV M184I 47 52 RT 135 137 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. In nondividing HLFs, the transduction of the M184I vector decreased 7.3-fold (to 8%), compared to the dividing cells (Figure 2A), and this is contrasted to the WT RT vector which displayed a similar transduction efficiency in both dividing (~80%) and nondividing HLFs (~70%) (Figure 1B). 2010 Virology Result HIV M184I 45 50 RT 163 165 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Indeed, both the M184I (+) and (-) cPPT vectors showed very similar IC50 values for AZT and NEV. 2010 Virology Result HIV M184I 17 22 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Indeed, the M184I vectors with higher ratios of co-packaged WT RT protein, exhibited an increased number of GFP expressing cells (Figure 3A), and thus a higher transduction efficiency (Figure 3B). 2010 Virology Result HIV M184I 12 17 RT 63 65 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. It was predicted that co-packaging of the WT HIV-1 RT together with the M184I RT within the same capsid could rescue the biochemical defects induced by the M184I RT mutation. 2010 Virology Result HIV M184I;M184I 72;156 77;161 Capsid;RT;RT;RT 97;51;78;162 103;53;80;164 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. M184I RT displays reduced polymerase activity and is clinically relevant due to its 3TC resistance. 2010 Virology Result HIV M184I 0 5 Pol;RT 26;6 36;8 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. M184I RT has been previously shown to have a high resistance to 3TC due to the steric hindrance between the isoleucine of RT and 3TC. 2010 Virology Result HIV M184I 0 5 RT;RT 6;122 8;124 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Next, we examined a 3TC dose dependence of with the M184I RT (+) and (-) cPPT vectors. 2010 Virology Result HIV M184I 52 57 RT 58 60 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Next, we investigated if the cPPT inactivation, which further reduced the transduction efficiency of the M184I vector in nondividing HLFs, directly impacted proviral DNA synthesis kinetics. 2010 Virology Result HIV M184I 105 110 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Next, we investigated possible mechanistic explanations of the 3TC sensitization effect of the cPPT inactivation in M184I vector. 2010 Virology Result HIV M184I 116 121 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Next, we investigated the effects of the cPPT mutation and cellular dNTP concentrations on the transduction of the HIV-1 vector bearing the M184I RT variant. 2010 Virology Result HIV M184I 140 145 RT 146 148 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Next, we tested if the reduced transduction of the M184I RT (-) cPPT vector in nondividing HLFs could be rescued by introducing WT RT molecules into the virion of the M184I vector. 2010 Virology Result HIV M184I;M184I 51;167 56;172 RT;RT 57;131 59;133 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Next, we tested if the same drug sensitization in the M184I (-) cPPT vector could be observed with AZT or Nevirapine. 2010 Virology Result HIV M184I 54 59 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Rescue of the M184I (-) cPPT mutation by WT RT molecules. 2010 Virology Result HIV M184I 14 19 RT 44 46 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Roles of the cPPT and cellular dNTP pools in a HIV-1 vector harboring the 3TC resistant M184I RT mutant. 2010 Virology Result HIV M184I 88 93 RT 94 96 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Since M184I (+) cPPT vector displays a high 3TC resistance, we were only able to determine the IC25 value, the drug concentration yielding 25% inhibition (Figure 4B). 2010 Virology Result HIV M184I 6 11 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. The cPPT mutation in the M184I vector induced a 2.6-fold transduction decrease in dividing cells, and this reduction is also very similar to the reduction observed with the WT vector (Figure 1B). 2010 Virology Result HIV M184I 25 30 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Therefore, it is apparent that the elevation of the cellular dNTP could significantly compensate the replicational delay induced by the M184I mutation and low dNTP concentration of the nondividing cells, leading to a larger increase (6.6x) of the M184I vector transduction efficiency in the nondividing cells treated with dNs, compared to the WT RT vector (1.5x, Figure 1B). 2010 Virology Result HIV M184I;M184I 136;247 141;252 RT 346 348 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. These data confirm that the cause of the decreased transduction efficiency of the M184I vector in nondividing cells was due to delayed reverse transcription resulting from the decreased polymerase kinetic activity of M184I RT, especially at low cellular dNTP pools found in nondividing cells. 2010 Virology Result HIV M184I;M184I 82;217 87;222 RT;Pol;RT 135;186;223 156;196;225 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. These data demonstrate that the drug sensitization effect of cPPT inactivation is exclusive to 3TC and the M184I (-) cPPT vector. 2010 Virology Result HIV M184I 107 112 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. They were transduced with M184I (+) and (-) cPPT vectors with the same p24 level (2.77x105 pg) used for the WT RT vectors in Figure 1B. 2010 Virology Result HIV M184I 26 31 p24;RT 71;111 74;113 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. This mutant appears transiently but consistently during 3TC treatment and ultimately results in M184V. 2010 Virology Result HIV M184V 96 101 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. This suggests that the sensitivity of the M184I (-) cPPT vector is exclusive to 3TC. 2010 Virology Result HIV M184I 42 47 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. To test this we investigated the effect of the cPPT mutation on the sensitivity of the M184I vector to 3TC. 2010 Virology Result HIV M184I 87 92 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. We prepared hybrid HIV-1 vectors, which have been previously described, harboring both WT and M184I RT molecules in different ratios within the same virion. 2010 Virology Result HIV M184I 94 99 RT 100 102 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. In order to confirm the integration deficiency afforded by the D64V point mutation, we generated the SVGmu-enveloped IDLV with FUGW as the transfer vector backbone (designated as FUGW/SVGmu(IN-)). 2010 Vaccine Result HIV D64V 63 67 IN 190 192 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. In this study, we introduced the D64V point mutation into the catalytic domain of the integrase gene. 2010 Vaccine Result HIV D64V 33 37 IN 86 95 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. The reduction of integration was approximately 432 folds (calculated as [IN(+) No (LV)]/[IN (No LV)]), consistent with the previous report showing that the D64V mutation can markedly reduce transgene integration by thousand-folds. 2010 Vaccine Result HIV D64V 160 164 IN;IN 73;91 75;93 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. A similar pattern was observed with N155H and Q148H using RDS 1997 and RDS 2197 (data not shown). 2010 Biochemistry Result HIV N155H;Q148H 36;46 41;51 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. All three inhibitors were able to trap SC and H-SC formed with N155H (Figure 7A) and Q148H (Figure 7B) to varying degrees after incubation for 3 h at 37 C. 2010 Biochemistry Result HIV N155H;Q148H 63;85 68;90 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Concerted integration catalyzed by Q148H was found to be resistant to all of the inhibitors to various degrees (Figure 8B). 2010 Biochemistry Result HIV Q148H 35 40 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Even though Q148H had significantly lower concerted integration activity than wt IN, the same trend of trapping SC by STIs appears to also occur (Figure 7B). 2010 Biochemistry Result HIV Q148H 12 17 IN 81 83 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Expectedly, Q148H had high resistance to RAL (16-fold) and EVG (20-fold) as compared to wt IN (Figure 8C). 2010 Biochemistry Result HIV Q148H 12 17 IN 91 93 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Formation of Trapped SC Produced by N155H and Q148H in the Presence of MK-2048, RAL, or EVG. 2010 Biochemistry Result HIV N155H;Q148H 36;46 41;51 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. HIV-1 carrying the N155H mutation in IN, replicates at ~70% efficiency relative to wt virus. 2010 Biochemistry Result HIV N155H 19 24 IN 37 39 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In addition with N155H, the total conversion of SC and H-SC to STC (Figure 6D) was slower in comparison to wt IN (Figure 6C). 2010 Biochemistry Result HIV N155H 17 22 IN 110 112 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In confirmation, the formation of FS products with N155H also followed similar delayed kinetics relative to wt IN (Figure 6E). 2010 Biochemistry Result HIV N155H 51 56 IN 111 113 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In contrast, N155H displayed overall slower assembly kinetics for SC and H-SC (Figures 6B and 6D). 2010 Biochemistry Result HIV N155H 13 18 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In contrast, the quantity of CHS products produced by Q148H was ~60 to 70% of wt IN level suggesting that this single 3'-OH processing step necessary for strand transfer was not severely affected under our assay conditions. 2010 Biochemistry Result HIV Q148H 54 59 IN 81 83 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In multiple experiments, formation of FS products by Q148H was delayed and reduced to ~30% level relative to wt IN upon incubation up to 3 h at 37 C (Supporting Information Figure S1). 2010 Biochemistry Result HIV Q148H 53 58 IN 112 114 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In multiple experiments, the N155H nucleoprotein complexes were generally delayed showing a maximum combined quantity for these two complexes between ~45 to 90 min (Figure 6D). 2010 Biochemistry Result HIV N155H 29 34 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In summary, MK-2048 is equally effective against wt IN and N155H for inhibition of concerted integration. 2010 Biochemistry Result HIV N155H 59 64 IN 52 54 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In summary, similar qualitative patterns for trapping of SC by STIs with wt, N155H, and Q148H IN were observed. 2010 Biochemistry Result HIV N155H;Q148H 77;88 82;93 IN 94 96 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In summary, the Q148H substitution decreased the ability of IN to promote concerted integration. 2010 Biochemistry Result HIV Q148H 16 21 IN 60 62 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In vivo, HIV-1 with the Q148H mutation possesses ~30% infectivity and ~15% replication capacity of wt virus. 2010 Biochemistry Result HIV Q148H 24 29 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. IN with a Q148H Mutation Possesses Markedly Reduced Concerted Integration Activity. 2010 Biochemistry Result HIV Q148H 10 15 IN 0 2 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. IN with the N155H Mutation Possesses Slower Assembly Properties for SC and Concerted Integration Kinetics than wt IN. 2010 Biochemistry Result HIV N155H 12 17 IN;IN 0;114 2;116 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. MK-2048 had a similar IC50 value for N155H (42 +- 3 nM) as wt IN (42 +- 5 nM) for inhibition of FS products (Table 1)(Figure 8A). 2010 Biochemistry Result HIV N155H 37 42 IN 62 64 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. MK-2048 was modestly active against Q148H with only a 2-fold higher IC50 value for inhibition of FS products. 2010 Biochemistry Result HIV Q148H 36 41 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. N155H is a primary mutation in IN that arises in patients undergoing RAL and EVG therapy. 2010 Biochemistry Result HIV N155H 0 5 IN 31 33 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Quantitative Analysis for Inhibition of Concerted Integration with N155H and Q148H. 2010 Biochemistry Result HIV N155H;Q148H 67;77 72;82 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The IC50 values for inhibition of FS products with N155H were 68 +- 15 nM and 87 +- 7.5 nM for RAL and EVG, respectively (Table 1). 2010 Biochemistry Result HIV N155H 51 56 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The N155H substitution provides greater resistance to EVG (10-fold) than RAL (3-fold) in comparison to wt IN (Table 1), as reported earlier. 2010 Biochemistry Result HIV N155H 4 9 IN 106 108 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The overall catalytic activity for strand transfer with recombinant IN with the Q148H mutation using LTR oligonucleotides as substrates was also ~30% of wt IN, after normalization of decreased 3'-processing activity. 2010 Biochemistry Result HIV Q148H 80 85 LTR;IN;IN 101;68;156 104;70;158 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The relative resistant profile of these inhibitors along with RDS 1997 and RDS 2197 against N155H as compared to wt IN were illustrated in Figure 8C. 2010 Biochemistry Result HIV N155H 92 97 IN 116 118 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The results suggest that the N155H mutation affects the ability of IN to properly assemble SC in a timely fashion and thus affect concerted integration which is at ~70% of wt levels. 2010 Biochemistry Result HIV N155H 29 34 IN 67 69 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Thus, the initial stage of STC formation by N155H (Figure 6D) was also delayed compared to wt IN (Figure 6B). 2010 Biochemistry Result HIV N155H 44 49 IN 94 96 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. We compared the assembly properties of SC using wt and N155H IN (Figure 6). 2010 Biochemistry Result HIV N155H 55 60 IN 61 63 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. We determined the resistance profile of N155H and Q148H against a spectrum of inhibitors including MK-2048, RAL, and EVG by studying their effect on forming trapped SC (Figure 7) and concerted integration activity (Figure 8). 2010 Biochemistry Result HIV N155H;Q148H 40;50 45;55 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. We quantitatively determined the interactions of MK-2048, RAL, and EVG with N155H and Q148H (Figure 8). 2010 Biochemistry Result HIV N155H;Q148H 76;86 81;91 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. A G913A substitution (NL4-3 numbering) was found in the matrix (MA) of NLDeltaSL1-D22, leading to an E42K amino acid change in the protein, and a C1907T substitution was found in the SP1 of NLDeltaSL1-D14, corresponding to a P10L substitution. 2010 Retrovirology Result HIV C1907T;E42K;G913A;P10L 146;101;2;225 152;105;7;229 Matrix;SP1;Matrix 56;183;64 62;186;66 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. It will be interesting to find out if the SP1 (T12I) revertant of the SL1-deleted BH10 also use similar mechanism to exclude spliced RNA from encapsidation and restore infectivity. 2010 Retrovirology Result HIV T12I 47 51 SP1 42 45 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. NL4-3 carrying the G913A (NL-913) or C1907T (NL-1907) mutation or both (NL-913/1907) was included for comparison. 2010 Retrovirology Result HIV C1907T;G913A 37;19 43;24 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. The mutant vectors were identical to the NLDeltaSL1 sequence, except that NLDeltaSL1-913 contained a G913A substitution in the MA gene, NLDeltaSL1-1907 had a C1907T mutation in the SP1 region and NLDeltaSL1-913/1907 harbored both mutations. 2010 Retrovirology Result HIV C1907T;G913A 158;101 164;106 SP1;Matrix 181;127 184;129 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. These results are consistent with a previous study demonstrating that HIV-1 of the BH10 strain acquires mutations in the MA (V35I) and SP1 (T12I) domains to compensate for the SL1 deletion. 2010 Retrovirology Result HIV T12I;V35I 140;125 144;129 SP1;Matrix 135;121 138;123 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. To verify the contribution of mutations G913A and C1907T to the enhanced infectivity of the SL1 mutant, we performed site-directed mutagenesis of NLDeltaSL1 to generate NLDeltaSL1-913, NLDeltaSL1-1907 and NLDeltaSL1-913/1907 strains. 2010 Retrovirology Result HIV C1907T;G913A 50;40 56;45 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. In contrast the IIQ/VTR83-85 substitutions or the single residue replacement (I84P) corresponding to DPT-Vpr2 and Vpr4 peptides respectively prevented detection of any PP2A1 subunit in the pull down samples. 2010 PloS one Result HIV I84P 78 82 Vpr;Vpr 105;114 108;117 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. M184V mutations were detected as early as 1.5 months of failure and at nearly every time point (39 of 40) tested. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 0 5 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. Mutations predicted to confer resistance to etravirine (E138A, Y181C, G190A) were present in five of the nine children with samples available in the first six months of failure; two of the seven children with samples in the seven to 12 month range had two etravirine associated mutations. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV E138A;G190A;Y181C 56;70;63 61;75;68 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. 3 positions were fully polymorphic with respect to the ROD reference (I180V/T, and D222N/K and L250I/V) independently of treatment experience, as previously described; and 3 positions were highly polymorphic: N30K/Q (100% of treatment-naive samples and 93% of the treatment-experienced samples), S39T/A (94% of the treatment-naive samples and 100% of the treatment-experienced samples) and I133V/A/T (84% of the treatment-naive samples and 100% of the treatment-experienced samples) (Figure 1). 2010 Retrovirology Result HIV D222K;D222N;I133A;I133T;I133V;I180T;I180V;L250I;L250V;N30K;N30Q;S39A;S39T 83;83;390;390;390;70;70;95;95;209;209;296;296 90;90;399;399;399;77;77;102;102;215;215;302;302 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. AA 34, a Lys in HIV-1, is involved in PIC binding; Arg was found at position 34 in the majority (42/45) of HIV-2 strains, and supported variability to the conserved R34K in 3 sequences. 2010 Retrovirology Result HIV R34K 165 169 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. After successive increases of RAL concentration, a variant carrying the Q91R and I175M mutations emerged in the population. 2010 Retrovirology Result HIV I175M;Q91R 81;72 86;76 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Although the Q91R substitution has been described previously as a IN polymorphism, this is the first time, to our knowledge, that these mutations are associated with resistance to RAL. 2010 Retrovirology Result HIV Q91R 13 17 IN 66 68 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. As shown in Figure 2, the Q91R and I175M substitutions conferred substantial phenotypic resistance to RAL in vitro with a 13.2-fold increase in mean IC50 (Mean IC50 ROD: 0.00395 nM, IC50 range: 0.0036-0.0043 nM; Mean IC50 ROD-Q91R + I175M: 0.0424 nM, IC50 range: 0.0358-0.054 nM). 2010 Retrovirology Result HIV I175M;I175M;Q91R;Q91R 35;233;26;226 40;238;30;230 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. At sampling time, in 2007, RAL was not commercially available, and HIV-2 patients were not included in RAL phase II-III clinical trials, arguing against the hypothesis that the N155 H mutation emerged as a resistance mutation per se or that an INI-resistant strain was transmitted. 2010 Retrovirology Result HIV N155H 177 183 IN 244 247 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Because the HIV-2 IN naturally harbors the AA that were mutated in HIV-1 IN under RTI pressure (V165 in HIV-1 is I165 in HIV-2, M154L in HIV-1 is I154 in HIV-2), it is possible that the HIV-2 IN sequence is naturally more prone to support the changes in RT induced by the emergence of RTI resistance mutations. 2010 Retrovirology Result HIV M154L 128 133 RT;RT;IN;IN;IN;RT 82;285;18;73;192;254 85;288;20;75;194;256 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Conservative polymorphisms S138T and A153 S were detected in 12% and 6% of all sequences respectively, but mutations S138A/K and A153Y, associated with decreased susceptibility to RAL and/or to EVG, were never detected. 2010 Retrovirology Result HIV A153S;A153Y;S138A;S138K;S138T 37;129;117;117;27 43;134;124;124;32 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Further experiments to assess the replicative capacity of these viruses would be required to assess the impact of Q96H/C/Y substitutions in the genetic context of HIV-2. 2010 Retrovirology Result HIV Q96C;Q96H;Q96Y 114;114;114 122;122;122 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. I175V and I175T polymorphisms were detected in samples from 4 patients and 1 patient respectively, but the I175M mutation was never detected (Figure 1). 2010 Retrovirology Result HIV I175M;I175T;I175V 107;10;0 112;15;5 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. In such a model, a positive charge at residue 91 could compromise the affinity between RAL and the enzymatic pocket and the I175M substitution may emerge to facilitate access of RAL to the enzymatic pocket. 2010 Retrovirology Result HIV I175M 124 129 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. It is possible that the genetic context of the ROD strain, or its relative replicative capacity in the presence of RAL, might favor the emergence of strains harboring the Q91R+I175M mutations over other resistance pathways including the Q148 H/R/K and/or N155 H substitutions. 2010 Retrovirology Result HIV I175M;N155H;Q148H;Q148R;Q91R 176;255;237;237;171 181;261;247;247;175 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Mutations V72I and V201I have been described to be selected in HIV-1 IN under EVG selective pressure in vitro , but their weight on compromising the response to EVG of patients infected with HIV-2 remains to be ascertained. 2010 Retrovirology Result HIV V201I;V72I 19;10 24;14 IN 69 71 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. No mutation described to be associated with INI-resistance in HIV-1 or HIV-2 was detected in our cohort, except for a N155 H substitution in the viral sequence from one treatment-experienced, INI-naive patient (Figure 1). 2010 Retrovirology Result HIV N155H 118 124 IN;IN 44;192 47;195 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Other polymorphisms previously described to favor the initiation of reverse transcription in HIV-2, such as the K127E and/or the V204I substitutions within IN, or to increase viral fitness, such as the RT V197I mutation were not detected in sequences from these patients, nor from any other patient. 2010 Retrovirology Result HIV K127E;V197I;V204I 112;205;129 117;210;134 RT;IN;RT 68;156;202 89;158;204 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Other resistance-associated mutations present in that sample included RT mutations M184V and S215Y, and PR mutations V33I, I50V, I54M and I89V. 2010 Retrovirology Result HIV I50V;I54M;I89V;M184V;S215Y;V33I 123;129;138;83;93;117 127;133;142;88;98;121 PR;RT 104;70 106;72 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Polymorphisms M154T and H157R at neighboring positions were detected only in the sample from this patient, and their impact is unknown. 2010 Retrovirology Result HIV H157R;M154T 24;14 29;19 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Presumably the presence of this mutation will compromise INI-based regimens, as the N155 H substitution has been associated with RAL-based therapy failure in HIV-2. 2010 Retrovirology Result HIV N155H 84 90 IN 57 60 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Q96 H was detected in sequences from 2 patients for which longitudinal samples were available: one patient maintained the Q96 H substitution after NRTI+PI-based therapy whereas the other patient evolved to a Q96C/Y mixture. 2010 Retrovirology Result HIV Q96C;Q96H;Q96H;Q96Y 208;0;122;208 214;5;127;214 NRTI;PI 147;152 151;154 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The phenotypic impact of the Q91R and I175M mutations on susceptibility to RAL was assessed in vitro using an MTT assay as described previously. 2010 Retrovirology Result HIV I175M;Q91R 38;29 43;33 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The Q91R mutation was detected in one isolate from one treatment-naive patient, and AA I175 was wild-type in that sample. 2010 Retrovirology Result HIV Q91R 4 8 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The Q96 H mutation has been described to increase infectivity in HIV-1 and in HIV-2 by improving specific interactions with other viral components comprising the initiation complex and thereby increasing the initiation of reverse transcription. 2010 Retrovirology Result HIV Q96H 4 9 RT 222 243 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. This variant outgrew an earlier transient variant harboring the I84I/R + L99L/I substitutions when cultured in the presence of 0.027 nM RAL, as well as the parental wild-type ROD strain when RAL concentration was increased to 0.082 nM. 2010 Retrovirology Result HIV I84I;I84R;L99I;L99L 64;64;73;73 70;70;79;79 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Viral replicative capacity did not seem to be affected by the Q91R and I175M mutations as the double mutant virus reached the same viral titer as the wild type virus in the absence of RAL pressure. 2010 Retrovirology Result HIV I175M;Q91R 71;62 76;66 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Altogether, these data confirm the underlying observation that the DAMs I54V and V82A cause less cell death than either WT HIV PR, or the other non-DAM mutants tested, confirming the reduced ability of protease containing DAMs to kill infected cells. 2010 PLoS pathogens Result HIV I54V;V82A 72;81 76;85 PR;PR 202;127 210;129 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. By contrast, D30N, F53L, and L90M all produced Casp8p41:gag-pol cleavage ratios greater than WT protease (Figure 8B). 2010 PLoS pathogens Result HIV D30N;F53L;L90M 13;19;29 17;23;33 PR;GagPol 96;56 104;63 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Casp8p41 content was greatest in HXB2 WT infected cells and in the L90M non-DAM infected cells. 2010 PLoS pathogens Result HIV L90M 67 71 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Consistent with our in vitro data infection with HIV containing the DAM mutations I54V or V82A resulted in reduced generation of Casp8p41. 2010 PLoS pathogens Result HIV I54V;V82A 82;90 86;94 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Consistent with the premise that mutations in HIV protease will reduce the ability of HIV protease to kill infected cells, protease containing V82A or I54V induced less apoptosis in infected cells than either WT or L90M (Figure 10A). 2010 PLoS pathogens Result HIV I54V;L90M;V82A 151;215;143 155;219;147 PR;PR;PR 50;90;123 58;98;131 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Expression of YFP alone or YFP with catalytically inactive YFP D25G PR resulted in minimal loss of transmembrane potential. 2010 PLoS pathogens Result HIV D25G 63 67 PR 68 70 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. For this we chose the DAMs I54V, V82A, and the non-DAMs K20R, L63P, D30N and L90M. 2010 PLoS pathogens Result HIV D30N;I54V;K20R;L63P;L90M;V82A 68;27;56;62;77;33 72;31;60;66;81;37 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. In addition, we introduced the control mutations of active site dead D25G, and T26S which has been shown to have reduced protease catalytic and cytotoxic activity. 2010 PLoS pathogens Result HIV D25G;T26S 69;79 73;83 PR 121 129 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. In contrast, YFP-PR fusions containing the DAMs I54V, V82A caused a lesser degree of transmembrane potential loss than WT-PR, that was similar to that of catalytically impaired T26S (Figure 3B). 2010 PLoS pathogens Result HIV I54V;T26S;V82A 48;177;54 52;181;58 PR;PR 17;122 19;124 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Infection with HXB2 containing the non-discordance associated mutation L90M caused a similar degree of loss of total cell viability, whereas infections with HXB2 containing the discordance associated mutations I54V or V82A caused significantly less loss of total cell viability. 2010 PLoS pathogens Result HIV I54V;L90M;V82A 210;71;218 214;75;222 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Mirroring the results of TMRE staining, I54V and V82A had reduced generation of active caspase 3 and caspase 3 activity than WT protease, while K20R, L63P, D30N, L90M, generated similar levels of active caspase 3 and of caspase 3 activity as WT (Figure 4A, 4B, 4C). 2010 PLoS pathogens Result HIV D30N;I54V;K20R;L63P;L90M;V82A 156;40;144;150;162;49 160;44;148;154;166;53 PR 128 136 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Of interest this trend was also observed in the uninfected cells, with less uninfected cell killing being observed with I54V, and a trend towards less death in the V82A protease mutant (Figure 10B). 2010 PLoS pathogens Result HIV I54V;V82A 120;164 124;168 PR 169 177 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Of interest, the two mutations (I54V and V82A) that are over represented in the discordant subjects had reduced cleavage of the Casp8p41 substrate compared to WT protease or D30N, F53L, or L90M, suggesting that these mutations have a selective impairment in the ability to generate Casp8p41, and therefore, an impairment in the ability to induce Casp8p41-dependent death (Figure 8A). 2010 PLoS pathogens Result HIV D30N;F53L;I54V;L90M;V82A 174;180;32;189;41 178;184;37;193;45 PR 162 170 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Strikingly, expression of YFP-L63P PR, YFP-D30N PR, YFP-K20R-PR, or YFP-L90M PR caused high degrees of transmembrane potential loss, similar to WT Protease. 2010 PLoS pathogens Result HIV D30N;K20R;L63P;L90M 43;56;30;72 47;60;34;76 PR;PR;PR;PR;PR 147;35;48;61;77 155;37;50;63;79 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Strikingly, only the I54V and V82A DAM mutations produced a ratio of Casp8p41:gag-pol cleavage that was significantly less than the ratio that was produced by WT HIV protease. 2010 PLoS pathogens Result HIV I54V;V82A 21;30 25;34 PR;GagPol 166;78 174;85 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. The putative impairment in cytotoxic activity of I54V and V82A were next assessed by an independent measure of death, generation of active caspase 3, and consequent caspase 3 activity. 2010 PLoS pathogens Result HIV I54V;V82A 49;58 53;62 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Therefore, if our model holds, the impaired cell killing associated with I54V and V82A protease expression, should be associated with less Casp8p41 production. 2010 PLoS pathogens Result HIV I54V;V82A 73;82 77;86 PR 87 95 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. These differences in total cell viability occurred despite similar levels of viral replication as reflected by similar levels of P24 antigen present in the culture supernatants, from the infections with the L90M, V82A, or I54V virus infections (Figure 9B). 2010 PLoS pathogens Result HIV I54V;L90M;V82A 222;207;213 226;211;217 p24 129 132 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. TUNEL staining confirmed these observations (Figure 5A, 5B) seen with TMRE staining and caspase 3 activity assays; the DAMs I54V, and V82A are associated with reduced induction of cell death compared to WT or the non-DAMs L63P, D30N, L90M, or K20R. 2010 PLoS pathogens Result HIV D30N;I54V;K20R;L63P;L90M;V82A 228;124;243;222;234;134 232;128;247;226;238;138 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. We have presented evidence that the DAM mutations I54V and V82A, have an impaired ability to cleave procaspase 8 relative to gag-pol. 2010 PLoS pathogens Result HIV I54V;V82A 50;59 54;63 GagPol 125 132 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. We tested WT HIV protease or the following point mutations: D25G (active site dead), T26S (catalytically impaired), D30N, F53L, or L90M; or the DAMs I54V and V82A produced in E-coli. 2010 PLoS pathogens Result HIV D25G;D30N;F53L;I54V;L90M;T26S;V82A 60;116;122;149;131;85;158 64;120;126;153;135;89;162 PR 17 25 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Whereas expression of YFP WT protease in primary CD4 T cells resulted in a significant proportion of Casp8p41 positive cells, expression of either I54V or V82A resulted in significantly less Casp8p41 positivity than K20R, L63P, D30N, or L90M (Figure 7A, 7B). 2010 PLoS pathogens Result HIV D30N;I54V;K20R;L63P;L90M;V82A 228;147;216;222;237;155 232;151;220;226;241;159 PR 29 37 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. YFP positive primary CD4 T cells containing I54V or V82A protease had significantly fewer apoptotic cells than YFP positive primary CD4 T cells containing WT, K20R, L63P, D30N or L90M protease (Figure 6). 2010 PLoS pathogens Result HIV D30N;I54V;K20R;L63P;L90M;V82A 171;44;159;165;179;52 175;48;163;169;183;56 PR;PR 57;184 65;192 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. By consensus genotyping, no US or Peru samples had the V75I substitution. 2011 The Journal of infectious diseases Result HIV V75I 55 59 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. No cases of T69N or M184I were observed. 2011 The Journal of infectious diseases Result HIV M184I;T69N 20;12 25;16 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. No cases of the V75I substitution were detected (95% confidence interval: 0-2.2%). 2011 The Journal of infectious diseases Result HIV V75I 16 20 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. OLA testing for the HIV-1 RT V75I mutation was performed on plasma samples from 168 HIV-1/HSV-2 dually-infected persons exposed to daily acyclovir or valacyclovir for between 8 weeks and 24 months, including 14 persons from the US, 31 from Peru, and 123 from Botswana/Kenya (Table 1). 2011 The Journal of infectious diseases Result HIV V75I 29 33 RT 26 28 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. Only two US samples had mutations conferring resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors (NRTIs or NNRTIs) - one with M184V and one with K103N; both of these mutations were present in enrollment visit samples, prior to acyclovir/valacyclovir exposure. 2011 The Journal of infectious diseases Result HIV K103N;M184V 168;149 173;154 NNRTI;NNRTI;NRTI 73;130;121 108;136;126 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. Sequence analysis of these seven samples demonstrated no cases of the GTA ATA substitution encoding V75I (Table 2). 2011 The Journal of infectious diseases Result HIV V75I 100 104 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. Analyzing the PLS regression equation further reveals that the over-predicted FDS for isolate 75739 versus AZT (shown as the AZT-75739 encircled point in bottom right corner of Figure 1) arises mainly due to an F77L mutation. 2010 PloS one Result HIV F77L 211 215 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. E.g., a pathway that the virus uses often to escape from thymidine analogs is by the mutation T215Y (or T215F), followed by M41L, which in turn is followed by L210W. 2010 PloS one Result HIV L210W;M41L;T215F;T215Y 159;124;104;94 164;128;109;99 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. Figure 3 presents screenshots of outputs from the web page, illustrating the predicted susceptibilities for two patterns of mutations: K65R+M184V (Panel A) and M41L+L210W+T215Y (Panel B). 2010 PloS one Result HIV K65R;L210W;M184V;M41L;T215Y 135;165;140;160;171 139;170;145;164;176 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. For example, mutations L210W and T215Y/F are the most deleterious for the thymidine analogues AZT and d4T, although they also reduce the susceptibility to the other NRTIs. 2010 PloS one Result HIV L210W;T215F;T215Y 23;33;33 28;40;40 NRTI 165 170 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. For example, mutations M184V/I and K65R, which are the most deteriorating for 3TC and FTC, lead to significant increase in susceptibility to AZT, thus suggesting a benefit of combining these inhibitors. 2010 PloS one Result HIV K65R;M184I;M184V 35;23;23 39;30;30 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. In contrast, some other mutations, such as Q151M exert similar influence on most of NRTIs (except on 3TC and FTC). 2010 PloS one Result HIV Q151M 43 48 NRTI 84 89 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. Moreover, the RT of isolate 75739 contains several atypical mutations, such as T215H, which is not present in any of the work-set sequences. 2010 PloS one Result HIV T215H 79 84 RT 14 16 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. On the other hand, the RT variant that harbors the triple mutation M41L+L210W+T215Y is highly resistant to AZT, while it shows an unchanged susceptibility to ddC and ddI. 2010 PloS one Result HIV L210W;M41L;T215Y 72;67;78 77;71;83 RT 23 25 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. Similarly, in three of the four virus isolates that were predicted falsely to be susceptible to 3TC, genotyping along with the wild type amino acid M identified also the mutant M184V. 2010 PloS one Result HIV M184V 177 182 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. Similarly, mutation M184V/I confers high resistance to the two structurally very similar inhibitors 3TC and FTC; it also affects susceptibility to ABC, DDC, and DDI, but is unimportant or even beneficial for AZT, d4T, and TDF. 2010 PloS one Result HIV M184I;M184V 20;20 27;27 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. We can there see that the double mutant K65R+M184V is highly resistant to 3TC and FTC, while it shows essentially unchanged susceptibility to d4T and TDF and is hypersusceptible to AZT. 2010 PloS one Result HIV K65R;M184V 40;45 44;50 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Accordingly, Vpu-A18H co-localized with BST-2 to a lesser degree than did wild type Vpu or the other Vpu mutants (Figure 3B, which shows quantitative image analysis and comparison of the Pearson coefficient of correlation between the signals for Vpu and BST-2). 2011 Virology Result HIV A18H 17 21 Vpu;Vpu;Vpu;Vpu 13;84;101;246 16;87;104;249 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. All of the Vpu TMD mutant-proteins exhibited similar cellular distributions and appeared to co-localize to a high degree with BST-2, with the exception of Vpu-A18H (Figure 3A). 2011 Virology Result HIV A18H 159 163 Vpu;Vpu 11;155 14;158 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. All other structures of BST-2/Vpu-A18H were above -300 kcal/mol. 2011 Virology Result HIV A18H 34 38 Vpu 30 33 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Although Vpu-I17A and Vpu-A18H have not been characterized for ion-channel activity, the proximity of the mutations to a hinge region or kink in the middle of the alpha-helical Vpu TMD suggested that these mutations might alter channel activity. 2011 Virology Result HIV A18H;I17A 26;13 30;17 Vpu;Vpu;Vpu 9;22;177 12;25;180 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. BFA caused wild type Vpu to adopt a similar sub-cellular distribution to Vpu-A18H and to co-localize more closely with calnexin (Figure 4A). 2011 Virology Result HIV A18H 77 81 Vpu;Vpu 21;73 24;76 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Complementation of DeltaVpu with Vpu-A18H resulted in a fractional p24 release of only 7.1%, a 1.7-fold enhancement relative to DeltaVpu alone (Figure 2A). 2011 Virology Result HIV A18H 37 41 p24;Vpu 67;33 70;36 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. However, the phenotype of Vpu-A18H could be due not only to mislocalization but also to a reduced ability to interact with BST-2. 2011 Virology Result HIV A18H 30 34 Vpu 26 29 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Immunofluorescence microscopy confirmed that Vpu-KKDQ exhibited an ER-like distribution and co-localized to an extent with calnexin; this distribution was similar to Vpu-A18H (Figure 6A). 2011 Virology Result HIV A18H 170 174 Vpu;Vpu 45;166 48;169 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Immunoprecipitation data indicated that the interaction between BST-2 and Vpu-KKDQ or Vpu-A18H was reduced relative to wild type Vpu (Figure 6F). 2011 Virology Result HIV A18H 90 94 Vpu;Vpu;Vpu 74;86;129 77;89;132 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In contrast, Vpu-A18F down-regulated BST-2 with an efficiency similar to the wild type (Figure 6B and D). 2011 Virology Result HIV A18F 17 21 Vpu 13 16 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In contrast, Vpu-A18F down-regulated CD4 with efficiency similar to wild type Vpu (Figure 6C and D). 2011 Virology Result HIV A18F 17 21 Vpu;Vpu 13;78 16;81 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In contrast, Vpu-A18F enhanced virion release by 6-fold, an activity almost equal to that of wild type Vpu (Figure 6E). 2011 Virology Result HIV A18F 17 21 Vpu;Vpu 13;103 16;106 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In contrast, Vpu-A18F exhibited a sub-cellular distribution more typical of the endosomal system and was similar to wild type Vpu (Figure 6A). 2011 Virology Result HIV A18F 17 21 Vpu;Vpu 13;126 16;129 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In contrast, Vpu-A18H essentially failed to down-regulate surface BST-2 (Figure 4B). 2011 Virology Result HIV A18H 17 21 Vpu 13 16 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In contrast, Vpu-S23L was previously characterized as defective for ion-channel activity. 2011 Virology Result HIV S23L 17 21 Vpu 13 16 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In support of the latter possibility, the Vpu-A18F protein also interacted somewhat less efficiently with BST-2 (Figure 3C), although its subcellular localization appeared normal (Figure 6A). 2011 Virology Result HIV A18F 46 50 Vpu 42 45 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Most interestingly, Vpu-A18H was dramatically impaired in the down-regulation of surface BST-2. 2011 Virology Result HIV A18H 24 28 Vpu 20 23 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Overall, these simulations indicated that Vpu-A18H has the potential to interact with BST-2 via its TMD, although the interaction is likely to be somewhat less stable than in the case of wild type Vpu. 2011 Virology Result HIV A18H 46 50 Vpu;Vpu 42;197 45;200 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Similar levels of down-regulation of surface BST-2 were achieved with the expression of the Vpu TMD mutant-proteins Vpu-I17A, -W22L, and -S23L (Figure 1C). 2011 Virology Result HIV I17A;S23L;W22L 120;138;127 124;142;131 Vpu;Vpu 92;116 95;119 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The data also indicated that the A18H substitution impairs the activity of Vpu as a BST-2 antagonist. 2011 Virology Result HIV A18H 33 37 Vpu 75 78 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The decreased ability of wild type Vpu to enhance virion release in the presence of BFA, along with phenotype of the Vpu-A18H mutant, suggests that the confinement of Vpu to the ER inhibits its ability to antagonize BST-2. 2011 Virology Result HIV A18H 121 125 Vpu;Vpu;Vpu 35;117;167 38;120;170 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The expression of Vpu-2/6, which contains two substitutions (S52N and S56N) in the DSGXXS motif within the cytoplasmic domain, resulted in an intermediate down-regulation of surface BST-2 expression consistent with previous findings (Figure 1A and C). 2011 Virology Result HIV S52N;S56N 61;70 66;74 Vpu 18 21 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The majority of cells expressing Vpu-A18H showed surface BST-2 levels comparable to those observed in cells transfected with the empty vector, although modest down-regulation of surface BST-2 was detectable at high expression (GFP) levels (Figure 1A and data not shown). 2011 Virology Result HIV A18H 37 41 Vpu 33 36 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The next most stable BST-2/Vpu-A18H assembly had a minimum distance of 13 A and a potential energy of -323.1 kcal/mol. 2011 Virology Result HIV A18H 31 35 Vpu 27 30 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The packing of BST-2 with wild type Vpu in these simulations was driven by contact of hydrophobic residues (Figure 7C), whereas in the lowest energy structure of BST-2/Vpu-A18H the histidine faces the backbone of BST-2 (Figure 7D). 2011 Virology Result HIV A18H 172 176 Vpu;Vpu 36;168 39;171 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The previous experiments suggested that confinement of Vpu to the ER, either through chemical means (BFA) or mutagenesis (A18H), results in impaired antagonism of BST-2. 2011 Virology Result HIV A18H 122 126 Vpu 55 58 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The TMDs maintained a stable helical conformation throughout a short 10 ns MD simulation after generating the ideal helices; the RMSD values leveled off after an initial rise within the first 1000 ps and remained in a range of 0.1 to 0.2 nm for BST-2 and 0.15 and 3.0 nm for the Vpu and Vpu-A18H helices (Supplemental Figure 1). 2011 Virology Result HIV A18H 291 295 Vpu;Vpu 279;287 282;290 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. These microscopic data supported the conclusion that Vpu-A18H mislocalizes to the ER, as does wild type Vpu in BFA-treated cells. 2011 Virology Result HIV A18H 57 61 Vpu;Vpu 53;104 56;107 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. This mislocalization might explain Vpu-A18H's impaired down-regulation of cell-surface BST-2, its inability to enhance virion release, and its reduced interaction with BST-2. 2011 Virology Result HIV A18H 39 43 Vpu 35 38 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. This reduced interaction could be solely the consequence of the mislocalization of Vpu-A18H, or the A18H substitution might also directly impair a putative direct interaction with the BST-2 TMD. 2011 Virology Result HIV A18H;A18H 87;100 91;104 Vpu 83 86 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Three of the generated substitutions exhibited frequencies of less than 1% [A18H (0%), W22L (0%), and S23L (0.06%)], while the I17A substitution appeared as a naturally occurring polymorphism with a frequency of 8.2%. 2011 Virology Result HIV A18H;I17A;S23L;W22L 76;127;102;87 80;131;106;91 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. To assess whether the Vpu-A18H TMD was intrinsically impaired in its potential to interact with the TMD of BST-2, we performed molecular dynamic (MD) simulations on the individual TMDs within hydrated lipid bilayers followed by a packing protocol to generate dimeric assemblies (Figure 7). 2011 Virology Result HIV A18H 26 30 Vpu 22 25 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. To confirm that the distribution of Vpu-A18H was consistent with residence in the ER, we co-stained cells for Vpu and calnexin, a calcium-binding protein located primarily in the ER. 2011 Virology Result HIV A18H 40 44 Vpu;Vpu 36;110 39;113 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. To evaluate the contribution of Vpu TMD domain residues, four Vpu TMD mutant-proteins were initially generated: Vpu-I17A, -A18H, -W22L, and -S23L. 2011 Virology Result HIV A18H;I17A;S23L;W22L 123;116;141;130 127;120;145;134 Vpu;Vpu;Vpu 32;62;112 35;65;115 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. To further explore the nature of the impaired antagonism of BST-2 exhibited by Vpu-A18H, co-immunoprecipitation was performed to measure the degree of interaction between the Vpu proteins and BST-2. 2011 Virology Result HIV A18H 83 87 Vpu;Vpu 79;175 82;178 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. To investigate the inability of the A18H mutant to down-regulate surface BST-2 expression and enhance virion release, we examined the subcellular distribution of the protein, as well as the other Vpu mutant-proteins characterized above, using immunofluorescence microscopy. 2011 Virology Result HIV A18H 36 40 Vpu 196 199 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. To resolve this, we tested two more Vpu mutants, Vpu-KKDQ and Vpu-A18F. 2011 Virology Result HIV A18F 66 70 Vpu;Vpu;Vpu 36;49;62 39;52;65 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18F is a single residue mutant that we thought might localize normally but interact poorly with BST-2. 2011 Virology Result HIV A18F 4 8 Vpu 0 3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18H and calnexin both exhibited a ring-like perinuclear and reticular cytoplasmic distribution, and the two proteins co-localized substantially (Figure 4A). 2011 Virology Result HIV A18H 4 8 Vpu 0 3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18H enhanced fractional p24 release by 2.6-fold in the absence of BFA and had almost no activity in the presence of BFA (Figure 4C; compare "DeltaVpu+BFA" to "A18H Vpu+BFA"). 2011 Virology Result HIV A18H;A18H 164;4 168;8 p24;Vpu;Vpu 29;0;169 32;3;172 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18H enhances virion release inefficiently. 2011 Virology Result HIV A18H 4 8 Vpu 0 3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18H exhibited a ring-like perinuclear as well as a reticular cytoplasmic distribution, consistent with residence in the ER, including the nuclear envelope. 2011 Virology Result HIV A18H 4 8 Env;Vpu 151;0 159;3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18H exhibits a cellular distribution consistent with residence in the endoplasmic reticulum and a reduced interaction with BST-2. 2011 Virology Result HIV A18H 4 8 Vpu 0 3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18H inefficiently down-regulates the expression of BST-2 at the cell surface. 2011 Virology Result HIV A18H 4 8 Vpu 0 3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-I17A, -A18H, -W22L, and -S23L all exhibited CD4 down-regulation similar to or better than wild type Vpu (Figure 1D). 2011 Virology Result HIV A18H;I17A;S23L;W22L 11;4;29;18 15;8;33;22 Vpu;Vpu 0;104 3;107 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-I17A, -W22L, -S23L, and Vpu 2/6 co-immunoprecipitated with BST-2 to the same extent as wild type Vpu, while Vpu-A18H exhibited a reduced interaction (Figure 3C). 2011 Virology Result HIV A18H;I17A;S23L;W22L 116;4;18;11 120;8;22;15 Vpu;Vpu;Vpu;Vpu 0;28;101;112 3;31;104;115 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-KKDQ was defective for the down-regulation of BST-2, appearing even more impaired than Vpu-A18H (Figure 6B and D). 2011 Virology Result HIV A18H 95 99 Vpu;Vpu 0;91 3;94 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-KKDQ was minimally impaired for the down-regulation of CD4, appearing less impaired than Vpu-A18H (Figure 6C and D). 2011 Virology Result HIV A18H 97 101 Vpu;Vpu 0;93 3;96 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-W22L was previously characterized as a functional ion-channel, although the durations between the open and closed conformations in artificial lipid bilayers were prolonged compared to the wild type Vpu. 2011 Virology Result HIV W22L 4 8 Vpu;Vpu 0;202 3;205 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. We also evaluated the capacity of Vpu-KKDQ and Vpu-A18F to down-regulate CD4 from the cell surface. 2011 Virology Result HIV A18F 51 55 Vpu;Vpu 34;47 37;50 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. We evaluated the capacity of Vpu-KKDQ and Vpu-A18F to down-regulate BST-2 from the cell surface. 2011 Virology Result HIV A18F 46 50 Vpu;Vpu 29;42 32;45 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Western blot confirmed that each of these Vpu mutants was expressed, although Vpu-KKDQ was expressed at levels slightly lower than that of the wild type (Figure 6F and Figure 3C regarding Vpu-A18F). 2011 Virology Result HIV A18F 192 196 Vpu;Vpu;Vpu 42;78;188 45;81;191 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. When the DeltaVpu provirus was co-transfected with plasmids expressing either wild type Vpu or the Vpu mutant-proteins, the fractional release of p24 was 29.2% for wild type Vpu, 28.8% for Vpu-I17A, 24.9% for Vpu-W22L, and 33.3% for Vpu-S23L, indicating a 6- to 8-fold enhancement of virion release (Figure 2A). 2011 Virology Result HIV I17A;S23L;W22L 193;237;213 197;241;217 p24;Vpu;Vpu;Vpu;Vpu;Vpu;Vpu 146;88;99;174;189;209;233 149;91;102;177;192;212;236 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. 5), and to a lesser extent in K70Q or Q151Mc RTs (not shown). 2011 PloS one Result HIV K70Q 30 34 RT 45 48 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Both Q151Mc and K70Q/Q151Mc enzymes incorporate dATP faster than WT (17.9 and 14.6 s-1, respectively vs. 2011 PloS one Result HIV K70Q 16 20 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Collectively, these results rule out the possibility that K70Q/Q151Mc becomes resistant to TFV through the excision mechanism. 2011 PloS one Result HIV K70Q 58 62 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Comparison of these models showed a significant repositioning of residue 65 in Q151Mc/K70Q. 2011 PloS one Result HIV K70Q 86 90 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Different mutations at this site have been previously implicated in NRTI resistance, suggesting that the observed K70Q mutation may be involved in the increased resistance to TFV-DF. 2011 PloS one Result HIV K70Q 114 118 NRTI 68 72 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Furthermore, K70Q is observed in 0.5% of the clinical samples from patients infected with HIV-1 Q151M. 2011 PloS one Result HIV K70Q 13 17 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Hence, the catalytic efficiency ratio of dATP incorporation remains similar for all enzymes (kpol-dATP/KD-dATP ratios for WT, K70Q, Q151Mc, and K70Q/Q151Mc were 2.4, 2.2, 3.3, and 2.9 microM-1 s-1, respectively). 2011 PloS one Result HIV K70Q;K70Q 126;144 130;148 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. In addition, HIV-1K70Q/Q151Mc displayed 5-fold increased resistance to TFV-DF compared to HIV-1Q151Mc. 2011 PloS one Result HIV K70Q 18 22 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. In addition, the ATP-based rescue activity of WT RT was saturated at lower concentrations of ATP than K70Q, Q151Mc, and K70Q/Q151Mc RTs (the apparent KD-ATP for WT, K70Q, Q151Mc and K70Q/Q151Mc were 0.4, 0.7, 2.3, and 3.1 mM, respectively), suggesting that a better binding of ATP may contribute to the slightly enhanced excision activity of WT RT. 2011 PloS one Result HIV K70Q;K70Q;K70Q;K70Q 102;120;165;182 106;124;169;186 RT;RT;RT 49;132;345 51;135;347 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. In addition, the turnover rates of TFV incorporation by the WT and K70Q enzymes were comparable (kpol-TFV were 2.8 and 3.1 s-1, respectively). 2011 PloS one Result HIV K70Q 67 71 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. In fact, excision enhancement due to the presence of ATP measured as [IC50 with ATP]/[IC50 without ATP] was similar for all enzymes, including the WT RT (from 2.7-fold to 2.9-fold for WT, K70Q, Q151Mc, and K70Q/Q151Mc RTs) (Table 1). 2011 PloS one Result HIV K70Q;K70Q 188;206 192;210 RT;RT 150;218 152;221 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. K70Q is rarely observed in treatment-naive patients (0.04%), but appears more often in clinical samples from NRTI-treated patients (0.1%, p<0.0001 compared with the frequency of K70Q in treatment-naive patients) but not NNRTI-treated patients. 2011 PloS one Result HIV K70Q;K70Q 178;0 182;4 NNRTI;NRTI 220;109 225;113 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Molecular dynamics simulations on the control structural coordinates of the WT RT/DNA/TFV-DP crystal structure did not cause any significant structural changes, suggesting that the modeling protocols do not alter the structures in ways that are not related to the K70Q or Q151Mc mutations. 2011 PloS one Result HIV K70Q 264 268 RT 79 81 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Notably, this isolate showed an increase in resistance to TFV-DF in the absence of the canonical TFV resistance mutation (K65R) and in the presence of Q151Mc mutations. 2011 PloS one Result HIV K65R 122 126 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Our extension assays in the absence of ATP (no-excision conditions) showed that addition of the K70Q mutation to Q151Mc HIV-1 RT enhances resistance to TFV-DP. 2011 PloS one Result HIV K70Q 96 100 RT 126 128 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. The addition of the K70Q mutation to Q151Mc also reduced the kpol for TFV-DP. 2011 PloS one Result HIV K70Q 20 24 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. The K70Q and K70Q/Q151Mc enzymes had more than 4.5-fold reduced affinity for TFV than the WT enzyme (KD-TFV values were 8.6 and 8.9 microM compared to 1.9 microM). 2011 PloS one Result HIV K70Q;K70Q 4;13 8;17 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. The net effect of these changes was a significant reduction in the TFV-DP incorporation efficiencies of the mutant enzymes compared to the WT enzyme (kpol-TFV/KD-TFV ratios for WT, K70Q, Q151Mc, and K70Q/Q151Mc were 1.47, 0.36, 0.3, and 0.11 microM-1 s-1, respectively; Table 2). 2011 PloS one Result HIV K70Q;K70Q 181;199 185;203 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. The results reveal that K70Q, Q151Mc, and K70Q/Q151Mc RTs have increased kpol-dATP as well as KD-dATP. 2011 PloS one Result HIV K70Q;K70Q 24;42 28;46 RT 54 57 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. The selectivity values demonstrate that the K70Q/Q151Mc enzyme favors incorporation of dNTP over TFV-DP 26.3 times compared to 1.6 times by the WT enzyme, leading to a 16.4-fold resistance to TFV (defined as selectivitymutant/selectivityWT; Table 2). 2011 PloS one Result HIV K70Q 44 48 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. There have been no previous reports on a possible role of K70Q in NRTI resistance. 2011 PloS one Result HIV K70Q 58 62 NRTI 66 70 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. This resistance is more than twice the TFV resistance of Q151Mc and 4 times the TFV resistance of K70Q. 2011 PloS one Result HIV K70Q 98 102 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. To determine whether the K70Q mutation causes TFV resistance through the excision mechanism we measured the susceptibility of WT and mutant RTs to inhibition by TFV in the presence or absence of ATP. 2011 PloS one Result HIV K70Q 25 29 RT 140 143 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. To determine whether the resistance by K70Q/Q151Mc is caused by an increased preference of physiological dATP substrate over TFV-DP, we carried out pre-steady state transient kinetic analyses of WT, K70Q, Q151Mc, and K70Q/Q151Mc enzymes. 2011 PloS one Result HIV K70Q;K70Q;K70Q 39;199;217 43;203;221 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. To examine the effect of K70Q on drug susceptibility we generated a series of HIV variants with mutations at RT codon 70 (Figure 2A and also Table S2). 2011 PloS one Result HIV K70Q 25 29 RT 109 111 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. We find that the ATP-based rescue activity of WT RT is not slower, but 1.5-, 2.5-, and 3-fold faster than that of K70Q, Q151Mc, and K70Q/Q151Mc RTs, respectively. 2011 PloS one Result HIV K70Q;K70Q 114;132 118;136 RT;RT 49;144 51;147 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. WT RT incorporated TFV-DP most efficiently, followed by K70Q>Q151Mc>K70Q/Q151Mc enzymes. 2011 PloS one Result HIV K70Q 68 72 RT 3 5 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. A Leu Ile change at RT codon 74 leads to a replication competent virus in the background of K65R (K65R+L74I) in PBM cells. 2011 Virology journal Result HIV K65R;K65R;L74I 92;98;103 96;102;107 RT 20 22 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. As largest cDNA band was 48 +- 6 nt for K65R+L74V RTs, we compared the densities for the largest group of bands (43-48) for all three RTs. 2011 Virology journal Result HIV K65R;L74V 40;45 44;49 RT;RT 50;134 53;137 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. As reverse transcription reactions with 6 mul of lysates resulted in most prominent cDNA band density with all three RTs (WT, K65R+L74V, K65R+L74I), we calculated statistical differences from lanes designated 6 in Figure 5. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 126;137;142;131 130;141;146;135 RT;RT 3;117 24;120 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. As shown in chromatogram (Figure 4), at RT codon 65 a significant increased R K reversion was observed for K65R+L74V virus in comparison to K65R+L74I viruses. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 107;140;145;112 111;144;149;116 RT 40 42 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. At low MOI of 0.001, no measurable growth (RT activity) of K65R+L74V viruses was noted until day 14 (Figure 1A). 2011 Virology journal Result HIV K65R;L74V 59;64 63;68 RT 43 45 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Based upon the RT activity (Figures 1A, 1B and 1C) the replication capacity of point mutants in three different MOIs (0.001, 0.01, 0.1) were: K65R (0.66, 0.57, 0.53), L74V (0.72, 0.81, 0.78), and L74I (0.79, 0.91, 0.82). 2011 Virology journal Result HIV K65R;L74I;L74V 142;196;167 146;200;171 RT 15 17 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Based upon the RT activity (Figures 1A, 1B and 1C), the relative replication capacities of double mutants with respect to WT virus on day 12 in three independent assays were: K65R+L74V [MOI 0.01, RC (0.10, 0.13, 0.11); MOI 0.1, RC (0.14, 0.16, 0.15), and K65R+L74I (MOI 0.01, RC (0.37, 0.42, 0.39); MOI 0.1, RC (0.40, 0.47, 0.44)]. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 175;255;260;180 179;259;264;184 RT 15 17 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Clearly, WT RT synthesized increased cDNA molecules resulting in a significant increase in densities of this group of bands (43-48) in comparison to K65R+L74V (p = 0.00007) and K65R+L74I (p = 0.0001). 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 149;177;182;154 153;181;186;158 RT 12 14 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Comparing extent of R K reversion on day 28 revealed a 19.8% and 66.2% reversion for K65R+L74I and K65R+L74V viruses respectively. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 85;99;90;104 89;103;94;108 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Comparison of R K reversion dynamics at codon 65 for doubly mutant K65R+L74V and K65R+L74I. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 67;81;86;72 71;85;90;76 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Comparison of replication kinetics plot revealed that the L I but not L V change at RT codon 74 in the background of K65R results in a replication competent virus. 2011 Virology journal Result HIV K65R 117 121 RT 84 86 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Control viruses with point mutations, K65R and L74V replicated inefficiently compared to wild type virus, as shown previously but replicated better than the double mutant K65R+L74I (Figure 2). 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 38;171;176;47 42;175;180;51 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Figure 4 shows that the reversion dynamics for K65R+L74I is clearly different than K65R+L74V viruses. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 47;83;52;88 51;87;56;92 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. However significant increase in the densities for larger bands (13-36) synthesized with K65R+L74I RT was obtained. 2011 Virology journal Result HIV K65R;L74I 88;93 92;97 RT 98 100 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. However, a significant increase in the densities of bands 25-30 was observed for WT RT in comparison to RTs of double mutants (WT/K65R+L74V, p = 0.001; WT/K65R+L74I, p = 0.01). 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 130;155;160;135 134;159;164;139 RT;RT 84;104 86;107 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In contrast to this K65R+L74V viruses showed a longer lag period and initiation of replication resulted in R K reversion as shown previously (5) (Figures 1A, 1B, 1C and 1D). 2011 Virology journal Result HIV K65R;L74V 20;25 24;29 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In contrast, K65R+L74I virus appears to be replication competent (Figure 1) and no visible reversion at RT codon 65 was observed until day 24 (8.8% reversion). 2011 Virology journal Result HIV K65R;L74I 13;18 17;22 RT 104 106 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In contrast, K65R+L74I viruses show a lag period of 5 days similar to WT and point mutants K65R, L74V and L74I. 2011 Virology journal Result HIV K65R;K65R;L74I;L74I;L74V 13;91;18;106;97 17;95;22;110;101 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In summary, K65R+L74I virus showed a shorter lag period (similar to WT and point mutants), increased RC and increased RT processivity in comparison to K65R+L74V viruses, suggesting a different structural constraint on RT with L I change. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 12;151;17;156 16;155;21;160 RT;RT 118;218 120;220 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Increased in vitro processivity of K65R+L74I RT in comparison to K65R+L74V RT. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 35;65;40;70 39;69;44;74 RT;RT 45;75 47;77 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. It should be emphasized, however, that K65R+L74V is a non-viable virus and R K reversion is related to the initiation of replication, suggesting this RT prefers natural dNTP 'A' (AAA, Lys) over 'G' (AGA, Arg) nucleotide for the survival of the virus. 2011 Virology journal Result HIV K65R;L74V 39;44 43;48 RT 150 152 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. No measurable RT activity was obtained until day 14 for the viruses with K65R+L74V mutations. 2011 Virology journal Result HIV K65R;L74V 73;78 77;82 RT 14 16 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Our analyses of comparative replication kinetics and in vitro processivity demonstrated that the improved replication capacity of K65R+L74I virus was due to an increase in the processivity of RT containing K65R+L74I mutant. 2011 Virology journal Result HIV K65R;K65R;L74I;L74I 130;206;135;211 134;210;139;215 RT 192 194 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Previous studies analyzing the risks and incidence of K65R and L74V mutations in the largest single clinic cohort in Europe (The Chelsea and Westminster HIV cohort) have demonstrated that the risk of developing L74V or K65R mutation during HAART was 4.5 and 2.8 cases per 100 person/year, respectively. 2011 Virology journal Result HIV K65R;K65R;L74V;L74V 54;219;63;211 58;223;67;215 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Similarly, RCs based on antigen p24 amount (Figure 1D) were: K65R (0.48), L74V (0.86), and L74I (0.90). 2011 Virology journal Result HIV K65R;L74I;L74V 61;91;74 65;95;78 p24 32 35 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Since the initiation of viral replication for K65R+L74V virus was observed after day 10, we compared RCs of two double mutant viruses on day 12. 2011 Virology journal Result HIV K65R;L74V 46;51 50;55 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Since visible reversion in sequence-chromatogram of K65R+L74V virus was observed on day 19, we performed population cloning for RNA isolated on days 19, 24 and 28 for both mutants. 2011 Virology journal Result HIV K65R;L74V 52;57 56;61 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The decreased frequency of selection of K65R and L74V and the rare occurrence of K65R+L74V on the same HIV genome may be related to the observed attenuation of the virus in the presence of these mutations. 2011 Virology journal Result HIV K65R;K65R;L74V;L74V 40;81;49;86 44;85;53;90 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The largest cDNA band for WT, K65R+L74V and K65R+L74I viruses were 66 +- 6, 48 +- 6, 54 +- 8 respectively. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 30;44;49;35 34;48;53;39 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The observed attenuated phenotype of viruses containing point mutations K65R and L74V was in agreement with previous documentations. 2011 Virology journal Result HIV K65R;L74V 72;81 76;85 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The paired analysis by student t-test showed a significant increase (p = 0.0004) in RC of K65R+L74I viruses in comparison to K65R+L74V viruses. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 90;125;95;130 94;129;99;134 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The pattern of growth curve (sigmoid) obtained with K65R+L74I viruses was similar to WT and point mutants in PBM cells. 2011 Virology journal Result HIV K65R;L74I 52;57 56;61 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The rapid reversion of K65R+L74V viruses is also in agreement with the observation that K65R+L74V virus has a longer lag period and abrupt initiation of replication coincides with the detection of R K revertants in PBM cells during replication of the virus. 2011 Virology journal Result HIV K65R;K65R;L74V;L74V 23;88;28;93 27;92;32;97 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The RCs for K65R+L74V and K65R+L74I viruses were 0.09 and 0.38 respectively based upon antigen p24 values of day 12 (Figure 1D). 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 12;26;31;17 16;30;35;21 p24 95 98 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The relative RCs were: WT > L74I > L74V > K65R > K65R + L74I > K65R + L74V. 2011 Virology journal Result HIV K65R;K65R;K65R;L74I;L74I;L74V;L74V 42;49;63;28;56;35;70 46;53;67;32;60;39;74 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The replication kinetics pattern in Figures 1B, 1C and 1D indicate a longer lag period of 10 days for the viruses with K65R+L74V mutations when infections were done at 0.01 and 0.1 MOIs. 2011 Virology journal Result HIV K65R;L74V 119;124 123;128 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The sequence analysis of 20 independent clones at each time point revealed that the rate of reversion was significantly high for K65R+L74V viruses in comparison to K65R+L74I viruses. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 129;164;169;134 133;168;173;138 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. These results demonstrated that the L I change at RT codon 74 improves the replication capacity of the K65R+L74I virus. 2011 Virology journal Result HIV K65R;L74I 103;108 107;112 RT 50 52 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. These results suggest that L74I change in the background of K65R leads to an RT which is much more stable as compared to RT with the K65R+L74V mutations. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 60;133;27;138 64;137;31;142 RT;RT 77;121 79;123 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Thus, L I change at RT codon 74 resulted in an increased processivity of RT with K65R mutation. 2011 Virology journal Result HIV K65R 81 85 RT;RT 20;73 22;75 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. To delineate the mechanisms involved in improved replication kinetics of K65R+L74I viruses in comparison to K65R+L74V viruses, we analyzed processivity of virion-associated RTs containing K65R+L74V, and K65R+L74I mutations in in vitro processivity assays. 2011 Virology journal Result HIV K65R;K65R;K65R;K65R;L74I;L74I;L74V;L74V 73;108;188;203;78;208;113;193 77;112;192;207;82;212;117;197 RT 173 176 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Viruses with L74I mutation replicated similar to L74V viruses. 2011 Virology journal Result HIV L74I;L74V 13;49 17;53 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We also performed paired student t-test analysis to determine increased density of cDNA bands synthesized by K65R+L74I RT in comparison to K65R+L74V RT. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 109;139;114;144 113;143;118;148 RT;RT 119;149 121;151 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We found no significant difference among densities of bottom six (1-6) bands between WT and K65R+L74V RTs (p = 0.38) and WT and K65R+L74I (p = 0.49) by paired student t-test analysis. 2011 Virology journal Result HIV K65R;K65R;L74I;L74V 92;128;133;97 96;132;137;101 RT 102 105 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We have previously demonstrated that L V substitution at RT codon 74 in the background of K65R results in a highly attenuated virus. 2011 Virology journal Result HIV K65R 90 94 RT 57 59 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We have recently shown that RT with K65R+L74V mutation has a significant decrease in in vitro RT processivity as compared to WT and RTs containing point mutations K65R and L74V. 2011 Virology journal Result HIV K65R;K65R;L74V;L74V 36;163;41;172 40;167;45;176 RT;RT;RT 28;94;132 30;96;135 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We observed slight increase in the RCs of L74I viruses as compared to L74V viruses in different assays but no statistical significance was noted. 2011 Virology journal Result HIV L74I;L74V 42;70 46;74 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Although the CCR5 expression in WT infection was somewhat higher than V38E mutant the results were not statistically significant (Figure 7C). 2011 Virology journal Result HIV V38E 70 74 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. As shown in Figure 1A, on days 3 and 5 post infection, numerous p24+ cells were seen in both WT and V38E virus infected cells, confirming infection. 2011 Virology journal Result HIV V38E 100 104 p24 64 67 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Both WT and V38E viruses mediate immune activation in CD8 cells. 2011 Virology journal Result HIV V38E 12 16 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. CCR5 upregulation in CD8 T cells is similar for WT and V38E infection. 2011 Virology journal Result HIV V38E 55 59 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Correlation of CD4 decline and HLADR (Figure 6A and 6B) or PD-1 (Figure 6C and 6D) expression on CD8 cells was determined for both the WT virus as well as V38E mutant. 2011 Virology journal Result HIV V38E 155 159 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Hence the V38E virus was both genotypically and more importantly phenotypically identical to the input virus. 2011 Virology journal Result HIV V38E 10 14 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Here again we saw that V38E, in fact, replicates much better than the WT virus (Figure 1G), consistent with our hypothesis that gp41 mutants with reduced cell-to-cell fusion activity are unable to induce bystander apoptosis and hence have more targets available for infection. 2011 Virology journal Result HIV V38E 23 27 gp41 128 132 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. However this correlation was not seen in the V38E infected groups (P > 0.05) (Figure 6B and 6D) where CD8 T cell immune activation is seen in the absence of significant CD4 decline. 2011 Virology journal Result HIV V38E 45 49 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Immune activation correlates with CD4 decline in WT virus but not V38E mutant. 2011 Virology journal Result HIV V38E 66 70 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. In a repeat of the study in a larger set of mice consisting of 6 mice per group the results were identical (Additional file 1, Figure S1), confirming the differential loss of CD4 cells in WT versus V38E infections. 2011 Virology journal Result HIV V38E 198 202 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. In fact, viral titers in the culture supernatants, determined by RT activity, was higher for V38E virus than WT on day 7 (Figure 1D). 2011 Virology journal Result HIV V38E 93 97 RT 65 67 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. In striking contrast, apoptotic cells were almost undetectable in the spleens of V38E virus infected mice (Figure 3B), even in the presence of similar levels of p24+ cells as in the WT group. 2011 Virology journal Result HIV V38E 81 85 p24 161 164 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Infection of activated CD4+ PBMCs with WT or V38E virus showed robust replication by both viruses. 2011 Virology journal Result HIV V38E 45 49 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. More importantly, we found that HLA-DR and PD-1 upregulation was seen in both the WT and V38E infected groups. 2011 Virology journal Result HIV V38E 89 93 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Quantitative analysis of at least 6 images from 2 different slides from each mouse confirmed that while both WT and V38E virus showed similar levels of p24 staining consistent with our cell line data and plasma viremia, there was little to no apoptosis in V38E infected mice (Figure 3C), suggesting that a single point mutation in gp41 (V38E) is enough to abrogate bystander apoptosis but not virus replication. 2011 Virology journal Result HIV V38E;V38E;V38E 116;256;337 120;260;341 gp41;p24 331;152 335;155 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Sequence analysis of proviral DNA also confirmed that the V38E virus had not reverted to WT virus after 8 weeks of infection and that there were no other changes in the gp41 region (Figure 4C). 2011 Virology journal Result HIV V38E 58 62 gp41 169 173 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Taken together, these findings suggest that V38E mutant is replication competent, yet deficient in inducing bystander apoptosis due to the limited fusion activity of the gp41 glycoprotein. 2011 Virology journal Result HIV V38E 44 48 gp41 170 174 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. The Enfuvirtide resistance of the V38E mutant was also confirmed in TZM cell line assay (Figure 1F). 2011 Virology journal Result HIV V38E 34 38 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. The fact that under similar experimental conditions V38E mutant failed to induce apoptosis in bystander cells suggests that bystander cell apoptosis induced by HIV infection is dependent on gp41 function. 2011 Virology journal Result HIV V38E 52 56 gp41 190 194 HIV infections 160 173 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. The limited CD4 decline in V38E infected group also suggests that immune activation and CD4 decline are probably not interdependent in the humanized mouse model. 2011 Virology journal Result HIV V38E 27 31 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. The recovered virus from each of the V38E virus infected mice showed lack of syncytia formation in contrast to WT virus that induced numerous syncytia (Figure 4B). 2011 Virology journal Result HIV V38E 37 41 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. The replication potential of V38E virus in PBMCs also suggested that it would be possible to conduct our studies in humanized mice to test the pathogenesis of the mutant. 2011 Virology journal Result HIV V38E 29 33 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. These findings suggest that CCR5 upregulation also does not vary between WT and V38E infections although a difference at the later stages of the infection beyond 20 weeks cannot be ruled out. 2011 Virology journal Result HIV V38E 80 84 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. To address this issue, we infected SupT1 cells with either WT or V38E virus and subsequently determined bystander cell death during active virus replication. 2011 Virology journal Result HIV V38E 65 69 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. To test the hypothesis that HIV Env mediated bystander apoptosis and CD4 decline are dependent on gp41 function, we used V38E mutant in comparison to WT virus. 2011 Virology journal Result HIV V38E 121 125 gp41;Env 98;32 102;35 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. V38E Env glycoprotein is restricted in bystander apoptosis induction in coculture experiments where Env expressing cells (Hela-Env) are cocultured with CD4 and CXCR4 expressing target cells (SupT1). 2011 Virology journal Result HIV V38E 0 4 Env;Env;Env 5;100;127 8;103;130 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. V38E mutant is attenuated in inducing CD4 decline in humanized mice. 2011 Virology journal Result HIV V38E 0 4 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. V38E mutant replicates in humanized mice without reverting to WT. 2011 Virology journal Result HIV V38E 0 4 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. V38E virus fails to induce bystander apoptosis in SupT1 cells even in the presence of active viral replication. 2011 Virology journal Result HIV V38E 0 4 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. We infected the BLT mice with 50,000 TCID50 of either WT or V38E virus and followed them for virus replication and CD4 decline, by measurement of CD4 T cell percentage from before infection to 8 weeks post infection. 2011 Virology journal Result HIV V38E 60 64 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. We next asked whether the replication potential of V38E virus is restricted to cell lines like SupT1 where the receptor and coreceptors are relatively high or the same phenomenon is also true for PBMCs. 2011 Virology journal Result HIV V38E 51 55 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. While peak viremia occurred in both WT and V38E infected mice by 6 weeks, the decline in CD4 counts was significantly higher in WT infected mice compared to V38E virus infected mice (Figure 2A). 2011 Virology journal Result HIV V38E;V38E 43;157 47;161 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. While the preceding data supports the hypothesis, we wanted to make sure that the V38E mutant had not reverted to WT in the 8-week infection period. 2011 Virology journal Result HIV V38E 82 86 21276267 Interplay between HIV entry and transportin-SR2 dependency. After membrane fusion (HIV-1 and measles virus envelope) or pH-independent endocytosis (MLVampho envelope), the N74D CA mutant still requires TRN-SR2 for infection of HeLaP4 cells. 2011 Retrovirology Result HIV N74D 112 116 Env;Env;Capsid 47;97;117 55;105;119 21276267 Interplay between HIV entry and transportin-SR2 dependency. Although we observed previously (Figure 4D) that the TRN-SR2 dependent phenotype of HIV-1 is more pronounced in prolonged multiple round infections, pseudotyping of the wild type and N74D CA mutant reporter viruses with different viral envelopes obliged single round infection experiments. 2011 Retrovirology Result HIV N74D 183 187 Env;Capsid 236;188 245;190 21276267 Interplay between HIV entry and transportin-SR2 dependency. As these findings suggest, the difference in TRN-SR2 dependency displayed by the N74D CA mutant in the multiple round compared with the single round infections was dependent on the envelope proteins; we investigated prolonged multiple round replication of the HIV-1 N74D CA mutant carrying a wild type envelope using HeLaP4 cells stably depleted of TRN-SR2 knockdown. 2011 Retrovirology Result HIV N74D 81 85 Env;Env;Capsid;Capsid 181;302;86;271 189;310;88;273 21276267 Interplay between HIV entry and transportin-SR2 dependency. HeLaP4 cells transiently depleted of TRN-SR2 and control cells were challenged with the differently pseudotyped WT and N74D CA mutant reporter viruses and infectivity was measured using the Fluc reporter protein activity as readout. 2011 Retrovirology Result HIV N74D 119 123 Capsid 124 126 21276267 Interplay between HIV entry and transportin-SR2 dependency. However, when the viral particles were pseudotyped with the HIV-1 envelope (Figure 6A), the MLVampho envelope (Figure 6B) or the measles virus envelope (Figure 6C), the N74D CA mutant was still dependent on TRN-SR2 (50% inhibition of infection in TRN-SR2 depleted cells), although not as dependent as the wild type virus (80-90% inhibition of infection). 2011 Retrovirology Result HIV N74D 169 173 Env;Env;Env;Capsid 66;101;143;174 74;109;151;176 21276267 Interplay between HIV entry and transportin-SR2 dependency. In repeated experiments using viruses carrying the HIV-1 envelope, we consistently observed a 1.5- to 3-fold higher infectivity of the N74D CA mutant measured via beta-galactosidase activity (data not shown). 2011 Retrovirology Result HIV N74D 135 139 Env;Capsid 57;140 65;142 21276267 Interplay between HIV entry and transportin-SR2 dependency. In repeated infection experiments, the VSV-G pseudotyped N74D mutant virus consistently displayed 5- to 10-fold higher luciferase counts than pseudotyped wild type virus (data not shown). 2011 Retrovirology Result HIV N74D 57 61 21276267 Interplay between HIV entry and transportin-SR2 dependency. In these experiments, the pseudotyped N74D CA mutant virus again proved to be more infectious than the wild type reporter virus (typically 10- to 15-fold). 2011 Retrovirology Result HIV N74D 38 42 Capsid 43 45 21276267 Interplay between HIV entry and transportin-SR2 dependency. Infection by the N74D CA mutant was inhibited 40% on average in the shTR3 cells, and 35% on average in the shTR4 cells (Figure 5D). 2011 Retrovirology Result HIV N74D 17 21 Capsid 22 24 21276267 Interplay between HIV entry and transportin-SR2 dependency. Interestingly, after normalization of the virus stocks based on p24 measurements (PerkinElmer, HIV-1 p24 ELISA kit), the VSV-G pseudotyped N74D CA mutant virus appeared 5-fold more infectious (compare Figures 3A and 3B). 2011 Retrovirology Result HIV N74D 139 143 p24;p24;Capsid 64;101;144 67;104;146 21276267 Interplay between HIV entry and transportin-SR2 dependency. Nevertheless, a prominent alteration in the TRN-SR2 dependency of the N74D CA mutant was observed when using the VSV-G envelope (complete insensitivity to TRN-SR2 knockdown, Figure 3B) or the HIV-1 envelope (intermediate sensitivity to TRN-SR2 knockdown, Figure 3D). 2011 Retrovirology Result HIV N74D 70 74 Env;Env;Capsid 119;198;75 127;206;77 21276267 Interplay between HIV entry and transportin-SR2 dependency. Next, we infected the HeLaP4 cells stably depleted of TRN-SR2 and control cells with two different dilutions of replication competent HIV-1 NL4-3 and N74D CA mutant virus normalized for p24 values (and RT activity) (Figures 5C and 5D). 2011 Retrovirology Result HIV N74D 150 154 p24;Capsid;RT 186;155;202 189;157;204 21276267 Interplay between HIV entry and transportin-SR2 dependency. Next, we wondered whether the inhibition of the N74D CA mutant by stable TRN-SR2 knockdown in the multiple round infection experiments could be mirrored in single round infection assays. 2011 Retrovirology Result HIV N74D 48 52 Capsid 53 55 21276267 Interplay between HIV entry and transportin-SR2 dependency. Subsequently, we infected HeLaP4 cells transiently depleted of TRN-SR2 with replication competent wild type and N74D mutant viruses. 2011 Retrovirology Result HIV N74D 112 116 21276267 Interplay between HIV entry and transportin-SR2 dependency. The infectivity of the VSV-G pseudotyped wild type and N74D CA mutant luciferase reporter viruses was measured by Fluc activity. 2011 Retrovirology Result HIV N74D 55 59 Capsid 60 62 21276267 Interplay between HIV entry and transportin-SR2 dependency. The N74D CA mutant was 2.5-fold more infectious than wild type HIV-1 in these experiments, corresponding to the increase in infectivity we observed in the experiments using transient siRNA-mediated knockdown of TRN-SR2 (Figures 3C and 3D). 2011 Retrovirology Result HIV N74D 4 8 Capsid 9 11 21276267 Interplay between HIV entry and transportin-SR2 dependency. The N74D mutant again yielded higher beta-galactosidase counts (compare Figures 3C and 3D), although the difference in infectivity was less pronounced (1.5-fold higher infectivity than wild type virus) than with the VSV-G pseudotyped N74D CA mutant (5- to 10-fold higher infectivity than wild type virus, compare Figures 3A and 3B). 2011 Retrovirology Result HIV N74D;N74D 4;234 8;238 Capsid 239 241 21276267 Interplay between HIV entry and transportin-SR2 dependency. The replication of both the HIV-1 wild type virus and the HIV-1 N74D CA mutant was severely impaired up to 10 days post infection in both shTR3 and shTR4 HeLaP4 cell lines stably depleted of TRN-SR2, although the N74D CA mutant was somewhat less sensitive to TRN-SR2 knockdown (10-fold inhibition in the shTR3 HeLaP4 cells compared to shSCR cells) than the wild type virus (70-fold inhibition in the shTR3 expressing cells compared to shSCR cells). 2011 Retrovirology Result HIV N74D 213 217 Capsid;Capsid 69;218 71;220 21276267 Interplay between HIV entry and transportin-SR2 dependency. The stable TRN-SR2 knockdown and control cell lines were challenged with wild type HIV-1 NL4-3 and N74D CA mutant virus in a multiple-round infection (Figure 4D), with the inocula normalized for p24 content. 2011 Retrovirology Result HIV N74D 99 103 p24;Capsid 195;104 198;106 21276267 Interplay between HIV entry and transportin-SR2 dependency. These results point to a partial TRN-SR2 dependency of the N74D CA mutant virus when carrying the HIV-1 envelope. 2011 Retrovirology Result HIV N74D 59 63 Env;Capsid 104;64 112;66 21276267 Interplay between HIV entry and transportin-SR2 dependency. To investigate whether endocytosis in general renders the HIV-1 N74D CA mutant insensitive to TRN-SR2 knockdown, we produced wild type and N74D CA mutant NL4-3 luciferase reporter virus pseudotyped with the HIV-1 envelope glycoproteins, VSV-G, or viral envelopes derived from the measles virus, amphotropic MLV or Ebola virus. 2011 Retrovirology Result HIV N74D 139 143 Env;Env;Capsid;Capsid 213;253;69;144 221;262;71;146 21276267 Interplay between HIV entry and transportin-SR2 dependency. To test this hypothesis, we infected HeLaP4 cells transiently depleted of TRN-SR2 with VSV-G pseudotyped wild type and N74D CA mutant luciferase reporter viruses (Figures 3A and 3B) or with replication competent HIV-1 NL4-3 wild type and N74D mutant virus (Figures 3C and 3D). 2011 Retrovirology Result HIV N74D;N74D 119;238 123;242 Capsid 124 126 21276267 Interplay between HIV entry and transportin-SR2 dependency. We confirmed the TRN-SR2 independent phenotype of the VSV-G pseudotyped N74D CA mutant (Figure 3B) in comparison to the pseudotyped wild type virus (75% reduction of viral infectivity on average in the TRN-SR2 knockdown cells compared to the mismatch siRNA transfected cells) (Figure 3A). 2011 Retrovirology Result HIV N74D 72 76 Capsid 77 79 21276267 Interplay between HIV entry and transportin-SR2 dependency. We observed that both HIV-1 NL4-3 WT virus (Figure 3C) and the N74D CA mutant (Figure 3D) required TRN-SR2 for efficient infection of HeLaP4 cells (average reduction of infectivity of 80% and 50% in TRN-SR2 knockdown cells, respectively), although the N74D CA mutant virus was less sensitive to TRN-SR2 depletion. 2011 Retrovirology Result HIV N74D;N74D 63;252 67;256 Capsid;Capsid 68;257 70;259 21276267 Interplay between HIV entry and transportin-SR2 dependency. We tested the infectivity of VSVG-pseudotyped wild type and N74D CA mutant virus, or replication competent wild type and N74D CA mutant viruses in single-round infection experiments in the HeLaP4 cells stably depleted of TRN-SR2 and in control cells. 2011 Retrovirology Result HIV N74D;N74D 60;121 64;125 Capsid;Capsid 65;126 67;128 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. A similar reduction in the formation of the ISD complex with RAL was obtained if wt IN and N155H IN were used from the HIV IIIB strain (data not shown) In summary, the results suggest that IN possessing the N155H mutation lacks the capacity to efficiently form the ISD complex in the presence of RAL but efficiently forms the ISD with MK-2048 and L-841,411 to which N155H IN is susceptible. 2011 Journal of molecular biology Result HIV N155H;N155H;N155H 91;207;366 96;212;371 IN;IN;IN;IN 84;97;189;372 86;99;191;374 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. A similar reduction was obtained with N155H even when incubation was increased to 3 h (data not shown). 2011 Journal of molecular biology Result HIV N155H 38 43 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. Formation of the ISD complex with RAL resistant IN mutant N155H depends upon the susceptibility to a particular STI. 2011 Journal of molecular biology Result HIV N155H 58 63 IN 48 50 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. In contrast, both L-841,411 and MK-2048 effectively formed the ISD complex with N155H at various inhibitor concentrations. 2011 Journal of molecular biology Result HIV N155H 80 85 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. MK-2048 inhibits both wt IN and N155H concerted integration activity with an IC50 value of 42 nM +- 3. 2011 Journal of molecular biology Result HIV N155H 32 37 IN 25 27 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. One primary resistant mutation occurs through the N155H pathway. 2011 Journal of molecular biology Result HIV N155H 50 55 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. Production of the ISD complex with the N155H mutant in the presence of RAL was reduced to approximately one-third the level of wt IN. 2011 Journal of molecular biology Result HIV N155H 39 44 IN 130 132 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. RAL resistance primarily occurs through several independent pathways containing mutations in IN (N155H and Q148H/K/R), with secondary mutations generally producing larger reductions in RAL susceptibility. 2011 Journal of molecular biology Result HIV N155H;Q148H;Q148K;Q148R 97;107;107;107 103;116;116;116 IN 93 95 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. RAL-resistant IN mutant N155H had a ~70% decreased capacity to produce the ISD complex in the presence of RAL in comparison to wt IN suggesting that the IN-single DNA complex has biological relevant properties. 2011 Journal of molecular biology Result HIV N155H 24 29 IN;IN;IN 14;130;153 16;132;155 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. The IC50 value to inhibit concerted integration catalyzed by IN containing the N155H mutation with RAL is ~3-fold higher than observed with wt IN. 2011 Journal of molecular biology Result HIV N155H 79 84 IN;IN 61;143 63;145 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. The IC50 values for RAL to inhibit wt IN and N155H IN concerted integration activities were 21 +- 4 nM and 68 +- 15 nM, respectively; the IC50 values for MK-2048 were 42 +- 5 and 42 +- 3 nM, respectively. 2011 Journal of molecular biology Result HIV N155H 45 50 IN;IN 38;51 40;53 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. The N155H mutation in HIV IN causes an increase susceptibility to L-841,411. 2011 Journal of molecular biology Result HIV N155H 4 9 IN 26 28 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. The N155H mutation in HIV IN decreased the capacity of RAL and MK-2048 to form the ISD complex but did not modulate L-841,411 ability to form and stabilize this complex. 2011 Journal of molecular biology Result HIV N155H 4 9 IN 26 28 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. The replication capacity of HIV containing the N155H mutation is ~70% of wt HIV which is similar to the specific activity for concerted integration activity of IN containing the N155H mutation in comparison to wt IN. 2011 Journal of molecular biology Result HIV N155H;N155H 47;178 52;183 IN;IN 160;213 162;215 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. The results suggest that a subtle structural change has occurred in IN via the N155H mutation affecting binding of RAL but did not significantly affect the ability of IN to promote concerted and CHS integration, or the replication capacity of the virus containing this mutation. 2011 Journal of molecular biology Result HIV N155H 79 84 IN;IN 68;167 70;169 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. There was a ~60% reduction in the formation of ISD with N155H in comparison to wt IN, both at 60 nM. 2011 Journal of molecular biology Result HIV N155H 56 61 IN 82 84 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. Under non-saturating (0.5 microM) and saturating (5 microM) concentrations of RAL for 2 h at 37 C, N155H was not able to efficiently form the ISD complex. 2011 Journal of molecular biology Result HIV N155H 99 104 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. We determined that IN containing the N155H mutation had a decreased capacity to form the ISD complex in the presence of RAL as compared to wt IN. 2011 Journal of molecular biology Result HIV N155H 37 42 IN;IN 19;142 21;144 21295584 HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex. We introduced the N155H mutation into the wt IN NY clone which does not contain any natural polymorphism for RAL resistance (data not shown) as observed in IN inhibitor-naive patients The specific activity of N155H for concerted integration is ~70% of wt IN using a 1.6 kb blunt-ended U5 DNA substrate. 2011 Journal of molecular biology Result HIV N155H;N155H 18;209 23;214 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Among the most prevalent mutations, reversion of M184V was associated with the largest DeltaRC. 2011 PloS one Result HIV M184V 49 54 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Among those 3 mutations, M184V had the fastest rate of reversion with 40% of patients showing dominant viral strains without this mutation after 2 months of STI. 2011 PloS one Result HIV M184V 25 30 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Figure 4-B shows the association between baseline RC and RC change after 2 months of STI for the mutation M184V. 2011 PloS one Result HIV M184V 106 111 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. In comparison, M41L and T215Y had a rate of reversion of 32% and 23% respectively within the same time period. 2011 PloS one Result HIV M41L;T215Y 15;24 19;29 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. In this latter tree, M184V was found to be the first mutation to revert. 2011 PloS one Result HIV M184V 21 26 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. More than 50% of the patients who still had M184V and L74V at 2 months saw an outgrowth of variants without those mutations. 2011 PloS one Result HIV L74V;M184V 54;44 58;49 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Notably, the mutation K103N had a high rate of reversion at both timepoints, with a reversion rate of 62% over the duration of the STI. 2011 PloS one Result HIV K103N 22 27 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Of all mutations studied, T215F showed the fastest reversion rate between baseline and 2 months, with 41% of the patients reversing this mutation (Table 1). 2011 PloS one Result HIV T215F 26 31 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Other mutations that were less frequent but associated with a large increase in RC included E44D, T69D, D67N, and 2 Non-Nucleoside RT inhibitors (NNRTI) mutations (namely V108I and Y181C). 2011 PloS one Result HIV D67N;E44D;T69D;V108I;Y181C 104;92;98;171;181 108;96;102;176;186 NNRTI;RT 146;131 151;133 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The emergence of viral strains without the mutation slowed down for other mutations, such as L210W, which reverted in 22% of the samples between baseline and 2 months, and in 14% between 2 and 4 months. 2011 PloS one Result HIV L210W 93 98 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The loss of M41L was most closely associated with the loss of several mutations, including L210W (0.96), T215Y (0.91), T69D (0.89) and V118I (0.78). 2011 PloS one Result HIV L210W;M41L;T215Y;T69D;V118I 91;12;105;119;135 96;16;110;123;140 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The most prevalent mutations at baseline were M41L (73.8% of patients), M184V, and T215Y (69%, 66.7% respectively). 2011 PloS one Result HIV M184V;M41L;T215Y 72;46;83 77;50;88 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The mutation M184V was most likely to revert concurrently with E44D, T69D, L210W and T215Y. 2011 PloS one Result HIV E44D;L210W;M184V;T215Y;T69D 63;75;13;85;69 67;80;18;90;73 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The rate of reversion of Y181C increased from 9% to 33%. 2011 PloS one Result HIV Y181C 25 30 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The reversion of mutations D67N and T215F was associated with K219Q. 2011 PloS one Result HIV D67N;K219Q;T215F 27;62;36 31;67;41 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The tree separated into two branches, one branch supported by M41L, T215Y and L210W, another branch containing K103N, T215F and K219Q. 2011 PloS one Result HIV K103N;K219Q;L210W;M41L;T215F;T215Y 111;128;78;62;118;68 116;133;83;66;123;73 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Viruses that reverted M184V between baseline and 2 months of STI and with baseline RC below 50% showed a median RC change of 82% (IQR = 55% - 108.7%), while viruses with baseline RC above 50% showed a median RC change of 39.5% (IQR = 21.5% - 46.7). 2011 PloS one Result HIV M184V 22 27 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? acquisition of L90M). 2011 AIDS research and therapy Result HIV L90M 15 19 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? At first, the impact of L76V on ATV- and SQV-resistance characteristics was assessed before and after establishment of the mutation. 2011 AIDS research and therapy Result HIV L76V 24 28 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Clinical outcome and follow-up in patients with L76V-adapted therapy. 2011 AIDS research and therapy Result HIV L76V 48 52 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Considering the effect of L76V on susceptibility for ATV and SQV, the big question was obviously, how this mutation might affect the therapeutic option and strategy for patients with a narrow margin of remaining active drugs. 2011 AIDS research and therapy Result HIV L76V 26 30 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Despite similar response rates at first, a sustained therapy success with virus suppression still below 50 copies/mL at week 96 and longer was predominantly achieved in group B patients where the selection pressure on L76V was constantly maintained by the drugs LPV or APV (Table 1, lower rows). 2011 AIDS research and therapy Result HIV L76V 218 222 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Due to the manifestation of the L76V mutation as well as other minor mutations at resistance-relevant sites in the course of treatment, genotype-based interpretation tools predicted intermediate or mostly complete resistance against all PIs including ATV and SQV and the majority of NRTIs and NNRTIs resulting in an active drug score (ADS) of <= 1.0 for the failing regimen (Figure 1). 2011 AIDS research and therapy Result HIV L76V 32 36 NNRTI;NRTI;PI 293;283;237 299;288;240 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Figure 2 supports this hypothesis on a variety of other patients harbouring HIV populations with L76V mutation. 2011 AIDS research and therapy Result HIV L76V 97 101 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? However, in particular, the copresence of the protease mutation L90 M was notably associated with high ATV and SQV resistance factors (Figure 2; #4, #26, #21). 2011 AIDS research and therapy Result HIV L90M 64 69 PR 46 54 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? In a further aspect, genotypic and phenotypic resistance data of 10 patients, all L76V positive, was assessed in order to analyze if these observed resensitizing effects represent ubiquitous drug resistance patterns. 2011 AIDS research and therapy Result HIV L76V 82 86 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? In most cases L76V appeared to be associated with a variety of other resistance relevant protease mutations without effecting the resensitizing effect. 2011 AIDS research and therapy Result HIV L76V 14 18 PR 89 97 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L90 M and further compensatory changes over the time (Figure 2; #4, #21, #26), making it crucial to suppress the virus completely and monitor viral load in close intervals. 2011 AIDS research and therapy Result HIV L90M 0 5 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? More interestingly, due to a loss of selection pressure on the L76V mutation, it was then undetectable in those patients who failed therapy, resulting in a decrease of the ADS below <2.0 (Table 3). 2011 AIDS research and therapy Result HIV L76V 63 67 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Patients with protease gene mutation L76V show increased susceptibility for Atazanavir and Saquinavir. 2011 AIDS research and therapy Result HIV L76V 37 41 PR 14 22 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Sufficient virus suppression below the detection limit was initially observed in 50% of group A (ATV and/or SQV without L76V-selecting drug) and 67% of group B (ATV and/or SQV plus L76V-selecting drug LPV or APV) within the first weeks of follow-up therapy. 2011 AIDS research and therapy Result HIV L76V;L76V 120;181 124;185 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Table 1 shows the L76V-adjusted follow-up therapies that were administered after resistance prediction results. 2011 AIDS research and therapy Result HIV L76V 18 22 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? These results additionally indicate benefits for patients with L76V-selecting drugs in combination with L76V-"resensitized" drugs. 2011 AIDS research and therapy Result HIV L76V;L76V 63;104 67;108 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? While L76V was undetectable in patients where no L76V-selecting drug was applied, it persisted in group B and group C where selection pressure on mutation L76V was maintained (Table 3). 2011 AIDS research and therapy Result HIV L76V;L76V;L76V 6;49;155 10;53;159 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. 293T cells were cotransfected with plasmids encoding ALIX and either HIV-1DeltaPTAP or HIV-1DeltaPTAP/S40F. 2011 Retrovirology Result HIV S40F 102 106 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. As described above, the S40F mutation increases the ratio of p25 to mature p24. 2011 Retrovirology Result HIV S40F 24 28 p24 75 78 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. As shown in Figure 8B, the S40F mutation had no influence on Env incorporation into virus particles. 2011 Retrovirology Result HIV S40F 27 31 Env 61 64 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. As we observed a deficiency in CA processing of p25 to p24 in the virions containing the S40F mutation (Figure 9), we investigated whether this defect in virus core assembly is a consequence of imperfect CA processing. 2011 Retrovirology Result HIV S40F 89 93 p24;Capsid;Capsid 55;31;204 58;33;206 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Considering this limitation in mutating p6, we wanted proof that the non-conservative S40F exchange does not disturb the secondary structure of p6 in the respective region. 2011 Retrovirology Result HIV S40F 86 90 Gag;Gag 40;144 42;146 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Consistent with previous results, the S40F mutation reduced the infectivity of released virions by ~5-fold (Figure 6B, 1 and 3). 2011 Retrovirology Result HIV S40F 38 42 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Defect in CA maturation of the S40F mutant can be rescued by mutation in the CA-SP1 cleavage site. 2011 Retrovirology Result HIV S40F 31 35 SP1;Capsid;Capsid 80;10;77 83;12;79 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Furthermore, the A1V/S40F mutant displayed a similar CA processing compared to the wt. 2011 Retrovirology Result HIV A1V;S40F 17;21 20;25 Capsid 53 55 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. However, in the case of the S40F mutant, introducing the A1V mutation largely improves virus core assembly (Figure 10B). 2011 Retrovirology Result HIV A1V;S40F 57;28 60;32 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. However, overexpression of ALIX did not restore the infectivity of the S40F mutant virions (Figure 6A, lane 4 lower panel), indicating that the loss of infectivity induced by mutation of Ser-40 occurs independently of the ALIX-p6 interaction. 2011 Retrovirology Result HIV S40F 71 75 Gag 227 229 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. However, quantification of the CA processing products p25 and p24 revealed a significant reduction in the processing rate of p25 to p24 for the S40F mutant (Figure 4C). 2011 Retrovirology Result HIV S40F 144 148 p24;p24;Capsid 62;132;31 65;135;33 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. In agreement with our biochemical data, accumulation of virions tethered at the cell membrane, a phenotype commonly observed for L-domain mutants in p6, was not observed for the S40F mutant (data not shown). 2011 Retrovirology Result HIV S40F 178 182 Gag 149 151 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. In contrast to the DeltaYP mutation, in the presence of the S40F mutation, overexpression of ALIX still efficiently rescued the release of the HIV-1DeltaPTAP mutant (Figure 6A, lane 4 upper panel). 2011 Retrovirology Result HIV S40F 60 64 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. In contrast, CA processing of the HIV-1DeltaPTAP/S40F mutant was further impaired, compared to the HIV-1DeltaPTAP mutant, and was not rescued by overexpression of ALIX (Figure 7A). 2011 Retrovirology Result HIV S40F 49 53 Capsid 13 15 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. In order to determine whether the ALIX mediated rescue of the HIV-1DeltaPTAP variant of the S40F is still comparable to the control, we measured the requirement of ALIX for HIV-1DeltaPTAP release at varying ALIX concentrations. 2011 Retrovirology Result HIV S40F 92 96 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Indeed, the phenotype observed for CA5 by analyzing the core structures of this mutant clearly resembles that of the S40F mutant (Figure 9A). 2011 Retrovirology Result HIV S40F 117 121 Capsid 35 37 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Introducing the A1V mutation enhances the specific infectivity of the virions of the otherwise attenuated S40F mutant to almost wt levels (Figure 10C), indicating that the deficiency in CA processing is the major determinant for the reduced infectivity of the S40F mutant. 2011 Retrovirology Result HIV A1V;S40F;S40F 16;106;260 19;110;264 Capsid 186 188 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. It was further reported that mutation of either Leu-41 or Leu-44 directly adjacent to Ser-40 exhibit a similar phenotype to that observed for the S40F mutant in terms of CA processing. 2011 Retrovirology Result HIV S40F 146 150 Capsid 170 172 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Moreover, the CA5 mutant, in which CA processing is blocked completely, shows the same phenotype as that of the S40F mutant, further supporting the notion that Ser-40 governs the processing of CA by a yet unidentified mechanism. 2011 Retrovirology Result HIV S40F 112 116 Capsid;Capsid;Capsid 14;35;193 16;37;195 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Next, we examined the effects of the S40F mutation on assembly, release, and virion morphology by thin-section electron microscopy (Figure 9). 2011 Retrovirology Result HIV S40F 37 41 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Parallel cultures of HeLa cells were transfected with the env-deleted HIV-1NL4-3 subgenomic expression vector pNLenv1, encoding either wt p6 or the S40F mutant. 2011 Retrovirology Result HIV S40F 148 152 Env;Gag 58;138 61;140 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Purified virus stocks of wt HIV-1NL4-3 and the S40F mutant were generated in 293T cells and normalized for p24 content. 2011 Retrovirology Result HIV S40F 47 51 p24 107 110 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. S40F mutation reduces specific infectivity of the virions. 2011 Retrovirology Result HIV S40F 0 4 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Since Ser-40 is located directly adjacent to Leu-41, we wanted to exclude that the reduced replication capacity and infectivity of the S40F mutant is due to reduced Env incorporation. 2011 Retrovirology Result HIV S40F 135 139 Env 165 168 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Subsequent determination of virus release by Western blot (Figure 7A) showed that in the presence of the S40F mutation similar amounts of ALIX were required to stimulate virus release (Figure 7A and 7B). 2011 Retrovirology Result HIV S40F 105 109 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Substitution of Ser-40 with Phe did not change the position or number of residues included in the C-terminal helix compared with wt sp623-52, and their structures appear to be similar. 2011 Retrovirology Result HIV S40F 16 31 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Taken together, the data indicate that the interaction of p6 with ALIX is not affected by replacing the conserved Ser-40 by Phe, and the phenotype induced by this mutation occurs independently of the ALIX mediated L-domain function of p6 in this region. 2011 Retrovirology Result HIV S40F 114 127 Gag;Gag 58;235 60;237 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The A1V mutation alone enhances the specific infectivity of the virons by 4-fold (Figure 10C). 2011 Retrovirology Result HIV A1V 4 7 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The A1V mutation had only marginal effects on the core morphology of wt HIV-1. 2011 Retrovirology Result HIV A1V 4 7 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The A1V mutation in the SP1, which previously was identified to confer resistance to the CA-maturation inhibitor Bevirimat, enhances the affinity of the viral protease to the CA-SP1 cleavage site. 2011 Retrovirology Result HIV A1V 4 7 PR;SP1;SP1;Capsid;Capsid 159;24;178;89;175 167;27;181;91;177 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The amount of MA and NC proteins in S40F mutant viruses was similar to that of wt virions, indicating that maturation of these Gag proteins is not affected by the S40F mutation (Figure 8A). 2011 Retrovirology Result HIV S40F;S40F 36;163 40;167 Gag;NC;Matrix 127;21;14 130;23;16 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The observation of NHi - NHi+1, NHi - NHi+2, alphaHi - NHi+ 2, alphaHi - NHi+ 3, alphaHi - NHi+ 4 and alphaHi - betaHi + 3 NOEs, which are indicative of helical secondary structure, showed that, similarly to wt sp623-52, sp623-52S40F has a preference for an alpha-helical structure involving residues Ile-31 - Asp-48 under hydrophobic membranous conditions (50% aqueous trifluorethanol (TFE) solution). 2011 Retrovirology Result HIV S40F 229 233 Asp 310 313 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The only possibility to leave the pol-ORF unaffected was to exchange Ser-40 for Phe, creating the mutant S40F. 2011 Retrovirology Result HIV F40S;S40F 69;105 83;109 Pol 34 37 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The S40F mutation again substantially increases the amount of virions containing aberrant, irregularly shaped virus cores. 2011 Retrovirology Result HIV S40F 4 8 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The S40F mutation does neither affect cleavage of Gag products, other than CA, nor incorporation of Env. 2011 Retrovirology Result HIV S40F 4 8 Env;Gag;Capsid 100;50;75 103;53;77 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. The S40F mutation was cloned into a variant of HIV-1NL4-3 where the PTAP motif was replaced by LIRL (HIV-1DeltaPTAP ). 2011 Retrovirology Result HIV S40F 4 8 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Therefore, virion structure of the A1V mutants was analyzed by thin-section electron microscopy. 2011 Retrovirology Result HIV A1V 35 38 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. This prompted us to investigate, whether restoring the CA processing by introducing specific mutations into the CA-SP1 cleavage site can rescue the defects in core assembly and infectivity induced by the S40F mutation. 2011 Retrovirology Result HIV S40F 204 208 SP1;Capsid;Capsid 115;55;112 118;57;114 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. This was further supported by the notion that the infectivity of the S40F mutant virions was substantially reduced and could not be restored by overexpression of ALIX (Figure 7C). 2011 Retrovirology Result HIV S40F 69 73 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Thus, the A1V mutation in SP1 was introduced into the HIV-1NL4-3 backbone in combination with the S40F mutation in p6. 2011 Retrovirology Result HIV A1V;S40F 10;98 13;102 SP1;Gag 26;115 29;117 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. To ascertain whether the S40F mutation alters the C-terminal helix of p6, the synthetic (s)p623-52S40F peptide was characterised by 1H NMR spectroscopy. 2011 Retrovirology Result HIV S40F;S40F 98;25 102;29 Gag 70 72 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. To further uncouple the phenotype induced by S40F mutation from the underlying L-domain function of the ALIX binding site, we investigated whether ALIX can rescue the infectivity of the S40F mutant in the context of a functional PTAP motif. 2011 Retrovirology Result HIV S40F;S40F 45;186 49;190 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. To this end, 293T cells were co-tranfected with HIV-1 encoding either wt p6 or the S40F mutant and ALIX. 2011 Retrovirology Result HIV S40F 83 87 Gag 73 75 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Western blot analysis of purified virions revealed that, by introducing the A1V mutation, CA processing is substantially enhanced in both, the wt and the S40F mutant virions (Figure 10A). 2011 Retrovirology Result HIV A1V;S40F 76;154 79;158 Capsid 90 92 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. While overexpression of ALIX had no significant influence on the infectivity of wt HIV-1 (Figure 6B, 2), ALIX also could not restore the reduced infectivity of the S40F mutant (Figure 6B, 4). 2011 Retrovirology Result HIV S40F 164 168 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. A baseline DNA sample was not available for patient 3, but the P145S mutations was absent from 25 integrase clones obtained from plasma virus at week 4. 2011 AIDS (London, England) Result HIV P145S 63 68 IN 98 107 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. Among the patients with a genotype result, three [7.7%, 95% confidence interval (CI) 1.6-20.9%] had INSTI resistance associated mutations consisting of N155H in two and P145S in one; all three were enrolled in the switch arm. 2011 AIDS (London, England) Result HIV N155H;P145S 152;169 157;174 INSTI 100 105 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. Plasma HIV-1 RNA levels for the two patients with N155H mutant virus remained below 200 copies/ml at months 34 and 17, respectively, on continued raltegravir treatment. 2011 AIDS (London, England) Result HIV N155H 50 55 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. The N155H mutation was detected in samples from two patients (#1 and #2) and the P145S mutation in one patient (#3). 2011 AIDS (London, England) Result HIV N155H;P145S 4;81 9;86 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. The N155H mutation was not detected in proviral DNA from PBMC obtained at entry from either patient. 2011 AIDS (London, England) Result HIV N155H 4 9 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. All of the pre-therapy mutations listed in Table 1 were also identified in the failure sample from the same patient except for one patient who did not have R358K in the failure sample. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV R358K 156 161 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. Only K103N and M184I/V were significantly more frequent at failure than pre-therapy (unadjusted p=0.001 and p=0.016, respectively). 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;M184I;M184V 5;15;15 10;22;22 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. Pre-therapy mutations associated with virologic failure, unadjusted for multiple comparisons, were E6D (p=0.023), K103R (p=0.046) and Q174K (p=0.015) in the polymerase domain and Q334H in the connection domain (p=0.045) [Table 2]. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV E6D;K103R;Q174K;Q334H 99;114;134;179 102;119;139;184 Pol 157 167 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. 3C) or two changes, M518V and F519L (Pattern II, 10/13 clones. 2011 Virology Result HIV F519L;M518V 30;20 35;25 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. 3D), with the H308P change being the only common feature among their V3 and gp120 sequences. 2011 Virology Result HIV H308P 14 19 gp120 76 81 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Among the Pattern-II clones, 5/13 contained the N406K change in V4 (data not shown). 2011 Virology Result HIV N406K 48 53 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Among the three clones with gp41 sequence Pattern I, one (R14) possessed only the H308P change, one had the K305R and H308P substitutions, while the third, lambda60, harbored all four V3 changes. 2011 Virology Result HIV H308P;H308P;K305R 82;118;108 87;123;113 gp41 28 32 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. An infectious clone derived from the fully resistant D101.12 isolate, D101.12 cl.14 (= R14), retained the H308P change in V3 that was also present in the CC101.6 input virus but had no other V3 changes compared to the parental isolate, CC1/85. 2011 Virology Result HIV H308P 106 111 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. And, as noted above, the R14 clone contained only the H308P change. 2011 Virology Result HIV H308P 54 59 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Approximately half (5/13) of the D101.12 clones contained all four of the resistance-associated V3 changes, but others possessed only three (3/13), two (4/13), or one of them (1/13); the H308P change was, however, invariably present in all the D101.12 clones. 2011 Virology Result HIV H308P 187 192 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. As noted above, most D101.12 clones were of gp41 sequence Pattern II, for which the important changes were M518V and F519L in the FP, together with the downstream V535M substitution. 2011 Virology Result HIV F519L;M518V;V535M 117;107;163 122;112;168 gp41 44 48 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Finally, the reversion-culture isolates consistently retained two of the four resistance-associated V3 changes (K305R and A316V), but the G321E change was consistently absent (i.e., it had reverted to the cognate parental sequence, 321G). 2011 Virology Result HIV A316V;G321E;K305R 122;138;112 127;143;118 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Hence when a proline is present at position 308, the V535M substitution reinforces the effects of the Pattern-I change in the FP (G514V), but not the Pattern-II changes (M518V, F519L). 2011 Virology Result HIV F519L;G514V;M518V;V535M 177;130;170;53 182;135;175;58 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Hence, the S+(G514V) virus, like S+(V535M), remained VCV sensitive. 2011 Virology Result HIV G514V;V535M 14;36 19;41 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. However, although the H308P change itself only modestly affects VCV sensitivity, it has a substantial influence on the outcome of additional V3 substitutions in this genetic context. 2011 Virology Result HIV H308P 22 27 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. In contrast to the reference X4 and R5X4 viruses (NL4-3 and CC2/86, respectively), the fully resistant clone R14 and the engineered resistant virus R14/S+(G514V, V535M) did not produce detectable amounts of p24 in CCR5-Delta32/Delta32 PBMC. 2011 Virology Result HIV G514V;V535M 155;162 160;167 p24 207 210 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. In contrast, making the same V535M change in R14/S (i.e., in the context of the H308P change in V3) caused a rightward shift of the dose-response curve, just as it did in PBMC. 2011 Virology Result HIV H308P;V535M 80;29 85;34 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. in the absence of H308P), they have a more pronounced effect than the combined Pattern-II changes (M518V, F519L, V535M), as manifested by the lower MPI value. 2011 Virology Result HIV F519L;H308P;M518V;V535M 106;18;99;113 111;23;104;118 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Introducing the Pattern II gp41 changes into the R14/S chimera, and hence in the context of the H308P change in V3, created a virus, R14/S+(M518V, F519L, V535M), that was only partially resistant. 2011 Virology Result HIV F519L;H308P;M518V;V535M 147;96;140;154 152;101;145;159 gp41 27 31 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Introducing the two Pattern-I gp41 changes (G514V + V535M) into the R14/S chimera that also harbors the H308P substitution mimicked the fully resistant phenotype of clone R14. 2011 Virology Result HIV G514V;H308P;V535M 44;104;52 50;109;57 gp41 30 34 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Introducing the V535M substitution, which is common to both gp41 patterns, into the parental clone S had no effect on the VCV infection-inhibition curve and the resulting MPI and IC50 values. 2011 Virology Result HIV V535M 16 21 gp41 60 64 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Most Pattern II clones (4/13) contained all four V3 substitutions, three had three changes (although not consistently in the same combination), while another three possessed the K305R and H308P changes. 2011 Virology Result HIV H308P;K305R 188;178 193;183 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Of note is that the resistance-relevant proline at residue 308 was absent from the reversion isolates, and although a change arose at this position, it was not to the dominant parental histidine, but to a new amino acid, threonine (i.e., P308T). 2011 Virology Result HIV P308T 238 243 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Of note, however, is that viruses harboring the gp41 Pattern-I changes, G514V and V535M, were more sensitive to the fusion inhibitor enfuvirtide (T20) than other viruses from this lineage, irrespective whether the H308P change in gp120 was present or not (SI. 2011 Virology Result HIV G514V;H308P;V535M 72;214;82 77;219;87 gp120;gp41 230;48 235;52 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Other changes were also evident at V3 positions adjacent to the first two established resistance-associated substitutions, although only the second of those changes (I309R) had become stabilized by passage 19. 2011 Virology Result HIV I309R 166 171 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Outside of V3, all three Pattern-I clones had lost a potential N-linked glycosylation site in the V4 region as a result of an N406K substitution (data not shown). 2011 Virology Result HIV N406K 126 131 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The dose-response curve for this virus was shifted to the left, similarly to the effect of the Pattern-I FP change creating the S+(G514V) virus (IC50 = 0.13 nM for both viruses). 2011 Virology Result HIV G514V 131 136 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The extent of replication with AMD3465, relative to its absence, did not differ between the VCV-sensitive viruses (S and R14/S) and -resistant viruses (R14 and R14/S+(G514V, V535M)), Mann-Whitney U two-tailed test for pooled replicates of each category, p=1.0. 2011 Virology Result HIV G514V;V535M 167;174 172;179 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The fully resistant phenotype of clone R14 was again mimicked by the introduction of the two Pattern-I gp41 changes (G514V + V535M) into the R14/S chimera. 2011 Virology Result HIV G514V;V535M 117;125 123;130 gp41 103 107 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The fully resistant R14 clone contains the H308P change in V3, but no other changes in this region, together with the Pattern-I gp41 substitutions, V535M + G514V. 2011 Virology Result HIV G514V;H308P;V535M 156;43;148 161;48;153 gp41 128 132 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The further addition of the V535M change to R14/S, creating the R14/S+(G514V, V535M) mutant made the virus replication-competent and rendered it fully resistant. 2011 Virology Result HIV G514V;V535M;V535M 71;28;78 76;33;83 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The further addition of V535M to make the triple mutant, S+(M518V, F519L, V535M) created a virus that was weakly resistant; its dose response curve was shifted rightward (IC50 = 0.71 nM), but with an MPI of 92 compared to 73 for S+(G514V, V535M). 2011 Virology Result HIV F519L;G514V;M518V;V535M;V535M;V535M 67;232;60;24;74;239 72;237;65;29;79;244 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The G514V and V535M changes generate robust resistance on both cell types when they are introduced together into the S clone, as does the single G514V change when it is made in the context of R14/S but not S (Table 3). 2011 Virology Result HIV G514V;G514V;V535M 4;145;14 9;150;19 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The high w value for R14 on TZM-bl cells, which indicates efficient use of the VCV-CCR5 complex, is largely reproduced for the R14/S+(G514V) and R14/S+(G514V, V535M) mutants and partly so for R14/S+(M518V, F519L, V535M) and R14/S+(M518V, F519L). 2011 Virology Result HIV F519L;F519L;G514V;G514V;M518V;M518V;V535M;V535M 206;238;134;152;199;231;159;213 211;243;139;157;204;236;164;218 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The inhibition plateau of this triple mutant was ~1.5-fold higher than that of the double mutant R14/S+(M518V, F519L) virus (MPI = 82 vs. 2011 Virology Result HIV F519L;M518V 111;104 116;109 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The introduction of the H308P single residue change into a parental, inhibitor-sensitive clone is known to confer low-level (~3-fold) resistance to AD101 and VCV. 2011 Virology Result HIV H308P 24 29 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The introduction of the two FP changes into the parental S clone created a VCV-sensitive virus, S+(M518V, F519L). 2011 Virology Result HIV F519L;M518V 106;99 111;104 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The Pattern-I change adds a bulky hydrophobic side-chain (G514V), whereas the other FP changes involve semi-conservative substitutions. 2011 Virology Result HIV G514V 58 63 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The R14/S+(G514V) single mutant was consistently able to replicate in TZM-bl cells, which contrasts with its replication-incompetence in PBMC (data not shown). 2011 Virology Result HIV G514V 11 16 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The resulting MPI values of 93 and 91 for R14/S+(M518V, F519L) and R14/S+(M518V, F519L, V535M) were comparable to that of R14/S, but the corresponding IC50 values of 1.0 nM and 1.9 nM were lower (Table 2). 2011 Virology Result HIV F519L;F519L;M518V;M518V;V535M 56;81;49;74;88 61;86;54;79;93 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The S+(G514V) single mutant and the S+(G514V, V535M) double mutant had similar MPI and IC50 values. 2011 Virology Result HIV G514V;G514V;V535M 7;39;46 12;44;51 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The S+(M518V, F519L) double mutant and the S+(M518V, F519L+V535M) triple mutant had similar MPI (>98) and IC50 (2.2 nM and 4.1 nM, respectively) values, the latter being ~7-fold lower than for S. 2011 Virology Result HIV F519L;F519L;M518V;M518V;V535M 14;53;7;46;59 19;58;12;51;64 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The same V535M change in the R14/S chimera created a virus, R14/S+(V535M), with a slightly higher IC50 value (0.45 nM vs. 2011 Virology Result HIV V535M;V535M 9;67 14;72 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The V535M change enhances the usage of VCV-CCR5 complexes for viruses with gp41-Pattern I sequences, but when it was added to the Pattern II-derived virus R14/S+(M518V, F519L) it reduced the w-value from 0.57 to 0.18. 2011 Virology Result HIV F519L;M518V;V535M 169;162;4 174;167;9 gp41 75 79 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The V535M substitution is common to all D101.12 isolates and clones, irrespective of which gp41 sequence pattern was present. 2011 Virology Result HIV V535M 4 9 gp41 91 95 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The VCV dose-response curve for R14/S+(G514V) was very similar to those of R14 and R14/S+(G514V, V535M), as were the corresponding MPI (85 vs. 2011 Virology Result HIV G514V;G514V;V535M 39;90;97 44;95;102 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The weak resistance of the R14/S chimera, which is attributable to the H308P change, is mainly manifested by the small (~6%), but consistent, level of replication that occurs at VCV concentrations as high as 5 muM (MPI = 94 for R14/S and 100 for S. 2011 Virology Result HIV H308P 71 76 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. There was also a new substitution (F317I) in the D101.12R19 virus, located adjacent to the third of the resistance-associated V3 changes, A316V. 2011 Virology Result HIV A316V;F317I 138;35 143;40 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. These two gp41 mutations are, however, necessary, but not sufficient, to confer resistance, since their insertion into the sensitive clone S resulted in only a partially resistant virus; hence, the MPI value of the engineered S+(G514V, V535M) mutant was reduced from 100 to 73. 2011 Virology Result HIV G514V;V535M 229;236 234;241 gp41 10 14 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. These types of profile were reproduced when the two fully resistant viruses, R14 and R14/S+(G514V, V535M), were included in the same eight experiments, each performed using PBMC from the same donor pair. 2011 Virology Result HIV G514V;V535M 92;99 97;104 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Thus, one or more of the three FP changes (G514V, M518V, F519L), but not V535M. 2011 Virology Result HIV F519L;G514V;M518V;V535M 57;43;50;73 62;48;55;78 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Thus, the R14/S chimera was only weakly resistant to VCV, which is consistent with its possession of the H308P change in V3. 2011 Virology Result HIV H308P 105 110 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Thus, the three later-arising V3 changes (K305R, A316V and G321E) confer complete resistance when introduced into a weakly resistant clone that contains proline at residue 308, but they have no effect on VCV sensitivity when the residue at this position is the predominant histidine. 2011 Virology Result HIV A316V;G321E;K305R 49;59;42 54;64;47 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Thus, the uncloned D101.12 isolate had all four resistance-associated V3 substitutions (K305R, H308P, A316V and G321E), but while the first two changes were fixed, the other two were unstable. 2011 Virology Result HIV A316V;G321E;H308P;K305R 102;112;95;88 107;117;100;93 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Thus, the VCV dose-response curve for R14/S+(G514V, V535M) was almost completely coincident with that of the reference, VCV-resistant clone R14. 2011 Virology Result HIV G514V;V535M 45;52 50;57 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Thus, when the gp41 Pattern-I changes (G514V + V535M) are combined in the context of the parental clone S. 2011 Virology Result HIV G514V;V535M 39;47 45;52 gp41 15 19 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. To further examine the genetics of resistance of the D101.12 isolate, we introduced the gp41 substitutions highlighted by the sequence analysis into both the parental, VCV-sensitive clone S and the weakly resistant R14/S chimera that contains the H308P change in V3. 2011 Virology Result HIV H308P 247 252 gp41 88 92 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Two clearly distinct patterns of gp41 sequences were apparent: A valine to methionine substitution at position 535 of the gp41 ectodomain (V535M) was present in all resistant isolates and clones, but it was accompanied by either a single G514V change in the FP (Pattern I, 3/13 clones. 2011 Virology Result HIV G514V;V535M;V535M 238;139;65 243;144;114 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Two distinct genetic lineages are apparent in gp41, together with a minimum of one (H308P), and up to all four, of the resistance-associated mutations in the gp120 V3 region. 2011 Virology Result HIV H308P 84 89 gp120;gp41 158;46 163;50 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. We can infer from these results that the full resistance of the R14 clone must, therefore, be attributable to the influence of the Pattern-I gp41 changes, acting in concert with the H308P change in V3. 2011 Virology Result HIV H308P 182 187 gp41 141 145 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. When only the G514V change was made in the S clone, the VCV dose-response curve was shifted to the left, resulting in a 6-fold lower IC50 value (0.13 nM vs. 2011 Virology Result HIV G514V 14 19 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. When the same G514V mutation was engineered in the context of the H308P change, the resulting R14/S+(G514V) virus was difficult to grow; it replicated sufficiently for its response to VCV to be properly quantifiable in only 3/11 of PBMC-based infection-inhibition assays. 2011 Virology Result HIV G514V;G514V;H308P 14;101;66 19;106;71 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. When we modeled the data set, derived from a single pair of PBMC donors, that displayed the most pronounced VCV-mediated infectivity enhancement, we obtained w values of 1.5 +- 0.11 for R14 and 1.6 +- 0.051 for R14/S+(G514V, V535M) (R2=0.81 and 0.87, respectively). 2011 Virology Result HIV G514V;V535M 218;225 223;230 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. with a high w value) were R14/S+(G514V, V535M) and R14/S+(M518V, F519L). 2011 Virology Result HIV F519L;G514V;M518V;V535M 65;33;58;40 70;38;63;45 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. 4F) under conditions where LPV inhibits processing of the single mutant TFR-PRL76V. 2011 Biochemistry Result HIV L76V 78 82 PR 76 78 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Autoprocessing of PRL76V and PRM46I/L76V Precursors. 2011 Biochemistry Result HIV L76V 36 40 PR;PR 18;29 20;31 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Autoprocessing was assessed in vitro with a precursor comprising the 56-amino acid TFR fused to the N-terminus of the PR domain containing the L76V mutation (TFR-PRL76V). 2011 Biochemistry Result HIV L76V 143 147 PR;PR 118;162 120;164 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. By contrast, in vitro phenotype assays found the mutation L76V in PR derived from clinical samples to be associated with enhanced susceptibility to SQV and resistance to DRV and LPV. 2011 Biochemistry Result HIV L76V 58 62 PR 66 68 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. For example, Tm values for ATV resistant mutant I50L/A71V and multi-drug resistant mutant V82F/I84V were both higher than the values observed for PR by 2.2 and 4 C, respectively. 2011 Biochemistry Result HIV A71V;I50L;I84V;V82F 53;48;95;90 57;52;99;94 PR 146 148 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. However, in many, if not most, DRV resistant clinical isolates, a single resistance mutation does not occur alone but is associated with other mutations such as M46I and L90M, which are selected along with L76V in clinical settings. 2011 Biochemistry Result HIV L76V;L90M;M46I 206;170;161 210;174;165 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. However, limited quantities of the precursor TFR-PRM46I/L76V could be obtained for comparison with TFR-PRL76V under the same conditions. 2011 Biochemistry Result HIV L76V;L76V 56;105 60;109 PR;PR 49;103 51;105 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. In PRL76V, Lys45 and Ile47 show reduced interactions with Val76, suggesting that M46I may indirectly compensate for the destabilizing effects of L76V. 2011 Biochemistry Result HIV L76V;M46I 145;81 149;85 PR 3 5 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. In the absence of inhibitors, TFR-PRM46I/L76V undergoes autoprocessing significantly faster. 2011 Biochemistry Result HIV L76V 41 45 PR 34 36 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Interestingly, however, TFR-PRM46I/L76V almost completely evades inhibition. 2011 Biochemistry Result HIV L76V;M46I 35;30 39;34 PR 28 30 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. L76V is associated with resistance to the inhibitors LPV, DRV, APV, and IDV, which form hydrogen bond interactions with Gly27, Asp29 and/or Asp30 near the catalytic Asp25, as well as the conserved water-mediated interactions with Ile50/50'. 2011 Biochemistry Result HIV L76V 0 4 Asp;Asp;Asp 127;140;165 130;143;168 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. NFV is the only exception with no direct flap interactions, however, susceptibility to NFV is less strongly associated with the L76V mutation compared to other drugs. 2011 Biochemistry Result HIV L76V 128 132 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Notably, although PRL76V shows a much slower rate of autoprocessing of its precursor relative to the wild type, in agreement with reported defective viral replication, the rate is increased upon introduction of M46I. 2011 Biochemistry Result HIV M46I 211 215 PR 18 20 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. On the other hand, inhibitors ATV, SQV and TPV, for which mutants containing L76V show increased susceptibility, all form direct or water-mediated hydrogen bond interactions with Gly48, while TPV is unique in forming direct, instead of water-mediated, hydrogen bonds with the amides of Ile50 and 50'. 2011 Biochemistry Result HIV L76V 77 81 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The additional M46I mutation has no effect on inhibition by 6 muM SQV or DRV. 2011 Biochemistry Result HIV M46I 15 19 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The mutation of leucine 76 to valine gives a shorter side chain, which results in the loss of several van der Waals contacts. 2011 Biochemistry Result HIV L76V 16 36 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The observed structural changes provide insight into the effects of combining mutation L76V with M46I, which has been reported to contribute strongly to competence of the virus to replicate and its clinical resistance to LPV. 2011 Biochemistry Result HIV L76V;M46I 87;97 91;101 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The properties of this mutant are discussed in relation to the interactions of the nine clinical inhibitors in order to understand why the L76V mutation is associated with increased resistance to some drugs while retaining effective binding affinity for other clinical inhibitors. 2011 Biochemistry Result HIV L76V 139 143 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. The single mutation L76V severely compromises viral replication in cell cultures, whereas coexistence of another mutation, M46I, was found to increase resistance to LPV while also partially restoring the ability of the virus to replicate. 2011 Biochemistry Result HIV L76V;M46I 20;123 24;127 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Thus, altered contacts with flap residues 45 and 47 associated with mutation L76V may partially diminish the binding affinity of LPV and contribute to resistance to this drug while having less effect on the other drugs. 2011 Biochemistry Result HIV L76V 77 81 21446746 The L76V drug resistance mutation decreases the dimer stability and rate of autoprocessing of HIV-1 protease by reducing internal hydrophobic contacts. Unfortunately, it was not possible to isolate the mature PRM46I/L76V because of its rapid autoproteolysis and very poor accumulation during its expression. 2011 Biochemistry Result HIV L76V 64 68 PR 57 59 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. A14C/E45C and P207C/T216C cores were isolated from virions in high yield (average of 44% of virion-associated CA, vs. 2011 PLoS pathogens Result HIV E45C;P207C;T216C;A14C 5;14;20;0 9;19;25;4 Capsid 110 112 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Although very few, a small number of P207C/T216C cores were observed in TRIM5alpharh treated samples, presumably due to low levels of spontaneous crosslinking of isolated P207C/T216C cores at the trimer interface. 2011 PLoS pathogens Result HIV P207C;P207C;T216C;T216C 37;171;43;177 42;176;48;182 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Both oxidized and non-oxidized P207C/T216C CA tubular assemblies bound TRIM5alpharh CC-SPRY, without any significant difference between them. 2011 PLoS pathogens Result HIV P207C;T216C 31;37 36;42 Capsid 43 45 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Despite the extensive CA hexameric crosslinking in A14C/E45C cores, incubation with TRIM5alpharh CC-SPRY resulted in a dramatic loss of intact cores observed by cryoEM, compared to the samples treated with the same amount of human TRIM5alpha CC-SPRY. 2011 PLoS pathogens Result HIV A14C;E45C 51;56 55;60 Capsid 22 24 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Following incubation with TRIM5alpharh CC-SPRY, crosslinked A14C/E45C CA assemblies exhibited only a slight reduction in CA hexamers. 2011 PLoS pathogens Result HIV A14C;E45C 60;65 64;69 Capsid;Capsid 70;121 72;123 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. For this purpose, we purified cores from the HIV-1 CA mutants A14C/E45C and P207C/T216C for two reasons; first, the mutant cores appeared to be more stable through the isolation procedure, and second, A14C/E45C and P207C/T216C cores bear the same cysteine mutations that we used for the in vitro analysis described in the previous section. 2011 PLoS pathogens Result HIV A14C;A14C;E45C;E45C;P207C;P207C;T216C;T216C 62;201;67;206;76;215;82;221 66;205;71;210;81;220;87;226 Capsid 51 53 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Importantly, the use of two mutants, A14C/E45C and P207C/T216C, containing engineered disulfide bonds, allowed us to assign the site of TRIM5alpharh action to the inter-hexamer interface (vs. 2011 PLoS pathogens Result HIV A14C;E45C;P207C;T216C 37;42;51;57 41;46;56;62 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. In contrast, no significant reduction in the number of P207C/T216C cross-linked cores was seen upon TRIM5alpharh incubation. 2011 PLoS pathogens Result HIV P207C;T216C 55;61 60;66 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. In previous work, we showed that introduction of a pair of cysteines, P207C/T216C, at the pseudo three-fold inter-hexamer interface, efficiently cross-linked three neighboring CA molecules into trimers upon oxidation. 2011 PLoS pathogens Result HIV P207C;T216C 70;76 75;81 Capsid 176 178 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Nonetheless, we tested for this possibility using a A14C/E45C CA double cysteine mutant, which can cross-link CA within hexamers. 2011 PLoS pathogens Result HIV A14C;E45C 52;57 56;61 Capsid;Capsid 62;110 64;112 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. S6, compare lanes 2 & 5), compared to the dramatic reduction of the trimer in the P207C/T216C CA assemblies. 2011 PLoS pathogens Result HIV P207C;T216C 82;88 87;93 Capsid 94 96 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. S6, lanes 2&8) in the oxidized A14C/E45C CA assemblies were observed by SDS-PAGE, possibly due to the CA CTD dimer interaction. 2011 PLoS pathogens Result HIV A14C;E45C 31;36 35;40 Capsid;Capsid 41;102 43;104 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. S7, -oxidizer), a four-fold decrease in the number of P207C/T216C cores was seen upon TRIM5alpharh treatment, compared to incubation with TRIM5alphahu. 2011 PLoS pathogens Result HIV P207C;T216C 54;60 59;65 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Several CA mutants, including A92E, which was used in our previous structural study, and the E45A mutant, which produces hyperstable capsids, were analyzed. 2011 PLoS pathogens Result HIV A92E;E45A 30;93 34;97 Capsid;Capsid 133;8 140;10 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. Such cross-linked P207C/T216C CA tubular assemblies are expected to contain stronger hexamer-hexamer interactions, stabilizing the lattice. 2011 PLoS pathogens Result HIV P207C;T216C 18;24 23;29 Capsid 30 32 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. The CA protein in A14C/E45C cores was readily cross-linked into hexamers, as shown by non-reducing SDS-PAGE analysis. 2011 PLoS pathogens Result HIV A14C;E45C 18;23 22;27 Capsid 4 6 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. The CA tubular assemblies carrying the capsid-stabilizing E45A mutation also experienced structural damage by TRIM5alpharh, but to a lesser degree. 2011 PLoS pathogens Result HIV E45A 58 62 Capsid;Capsid 39;4 45;6 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. The effect of TRIM5alpharh CC-SPRY binding to A92E CA tubular assemblies was similar to that observed with wild-type CA. 2011 PLoS pathogens Result HIV A92E 46 50 Capsid;Capsid 51;117 53;119 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. The P207C/T216C mutant assembles into tubular structures very similar to the wild-type CA. 2011 PLoS pathogens Result HIV P207C;T216C 4;10 9;15 Capsid 87 89 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. We further tested this possibility by measuring the cross-linking efficiency of P207C/T216C CA assembly after TRIM5alpharh CC-SPRY treatment. 2011 PLoS pathogens Result HIV P207C;T216C 80;86 85;91 Capsid 92 94 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. Of the 16 infants with HIV drug resistance mutations at 6 mo, 13 (81%) had at least one NRTI resistance mutation (M184 I/V [n = 12], K65R [n = 2], and D67G [n = 1]), and six (38%) had NNRTI resistance mutations (K103N [n = 2], Y181 [n = 2], and G190A [n = 2]) (sequences submitted to GenBank, http://www.ncbi.nlm.nih.gov/Genbank/index.html, accession numbers HM164112-HM164123, HM164127-HM164128, and HM164130-HM164131) (Table 3). 2011 PLoS medicine Result HIV D67G;G190A;K103N;K65R;M184I;M184V 151;245;212;133;114;114 155;250;218;137;123;123 NNRTI;NRTI 184;88 189;92 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. At 14 weeks of age, 82 (75.9%) of 108 infants had NVP resistance detected with the ViroSeq assay and 78 (72.2%) had K103N and/or Y181C detected with the LigAmp assay (P=0.45, McNemar's test, Figure 1A). 2011 AIDS (London, England) Result HIV K103N;Y181C 116;129 121;134 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. extended NVP+ZDV study arms who had detectable K103N or Y181C at either 6 or 12 months (P=1.0 at 6 months, P=0.43 at 12 months, Fisher's exact test, Figure 1B). 2011 AIDS (London, England) Result HIV K103N;Y181C 47;56 52;61 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. Five infants had NVP resistance mutations other than K103N and Y181C detected by ViroSeq at 14 weeks (V106A, Y188C/L, G190A) in the absence of K103N or Y181C. 2011 AIDS (London, England) Result HIV G190A;K103N;K103N;V106A;Y181C;Y181C;Y188C;Y188L 118;53;143;102;63;152;109;109 123;58;148;107;68;157;116;116 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. Nineteen (66.5%) of the 29 infants who were included in the analysis still had K103N and/or Y181C detected at 12 months of age (Figure 1B). 2011 AIDS (London, England) Result HIV K103N;Y181C 79;92 84;97 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. There was no significant difference in the level of K103N or Y181C detected in the infants in these two groups at the 6- or 12-month visits (data not shown). 2011 AIDS (London, England) Result HIV K103N;Y181C 52;61 57;66 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. Thirty-eight (82.6%) of the 46 infants still had K103N and/or Y181C detected at 6 months of age. 2011 AIDS (London, England) Result HIV K103N;Y181C 49;62 54;67 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. Three of the four infants did not have any NVP resistance mutations detected in the 6-month sample; in one infant, G190A was detected. 2011 AIDS (London, England) Result HIV G190A 115 120 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. We next used the LigAmp assay to analyze persistence of K103N and Y181C in infants who had those mutations detected at 14 weeks of age. 2011 AIDS (London, England) Result HIV K103N;Y181C 56;66 61;71 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. 20%; P < 0.01), with M41L/LM mutations being the most strongly associated (38% vs. 2011 International health Result HIV M41L;M41M 21;21 28;28 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. Of the NRTI mutations, M184V was the predominant mutation (65%), followed by TAMs (44; 48%). 2011 International health Result HIV M184V 23 28 NRTI 7 11 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. Y181C (37%) was the predominant NNRTI mutation, followed by K103N (26%) and G190A (18%). 2011 International health Result HIV G190A;K103N;Y181C 76;60;0 81;65;5 NNRTI 32 37 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. 1A, all of the Gag mutants were capable of inhibiting WT virus, with pNL4-3/Y164A being the most potent and pNL4-3/1GA being the least. 2011 Virology Result HIV Y164A 76 81 Gag 15 18 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. 2A, the MA mutant 1GA and the CA mutants Q155N and Y164A (consistent with ) were severely defective in virus release by themselves. 2011 Virology Result HIV Q155N;Y164A 41;51 46;56 Matrix;Capsid 8;30 10;32 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. 3B, both V513E and R515A Env mutants were severely defective in cell-to-cell fusion and consequently apoptosis induction when compared to WT Env. 2011 Virology Result HIV R515A;V513E 19;9 24;14 Env;Env 25;141 28;144 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. 4A, the 1GA mutant most significantly affected membrane localization of WT Gag (diffuse staining) followed by Y164A and Q155N. 2011 Virology Result HIV Q155N;Y164A 120;110 125;115 Gag 75 78 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. 6B, the dominant negative effect of HIV CTDel/R515A was significantly less than R515A in virus cell fusion assays. 2011 Virology Result HIV R515A;R515A 46;80 51;85 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. 7B) were expanded in vitro and subsequently transduced with either a lentiviral vector expressing GFP (TyEFeGFP) or the Y164A/R515A DN mutant. 2011 Virology Result HIV R515A;Y164A 126;120 131;125 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. 7E and S5D) showed significantly reduced virus replication over time with the lentivirus vector expressing the Y164A/R515A mutant when compared to cells transduced with TyEFeGFP vector in 2 independent experiments. 2011 Virology Result HIV R515A;Y164A 117;111 122;116 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. A similar defect was also seen with the Y164A Gag mutant but to a lesser extent. 2011 Virology Result HIV Y164A 40 45 Gag 46 49 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Among the Env mutants, both Lai/V513E and Lai/R515A effectively inhibited WT with the former being a slightly better inhibitor. 2011 Virology Result HIV R515A;V513E 46;32 51;37 Env 10 13 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. As anticipated, the R515A mutation has no effect on release of WT virus from cells. 2011 Virology Result HIV R515A 20 25 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. As shown in Fig.7A, expression from the lentivirus expressing Gag-Y164A alone was significantly reduced compared to the lentivirus expressing Gag and Env Y164A/R515A together presumably due to lack of Rev protein and Rev responsive element (RRE) that functions in regulating the transport of the full-length and partially spliced HIV RNAs out of the nucleus. 2011 Virology Result HIV R515A;Y164A;Y164A 160;66;154 165;71;159 Rev;Rev;Env;Gag;Gag 201;217;150;62;142 204;220;153;65;145 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. First we looked at the mechanism of R515A mediated inhibition of WT virus infectivity by examining whether it interfered with gp160 processing. 2011 Virology Result HIV R515A 36 41 gp160 126 131 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. For these ex vivo studies we cloned the Gag-Y164A and Env-R515A mutant into a lentivirus vector. 2011 Virology Result HIV R515A;Y164A 58;44 63;49 Env;Gag 54;40 57;43 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. For this purpose we chose the R515A mutation with the uncleaved Env as a potential therapeutic candidate for combination with various Gag mutants because, unlike the V513E mutant, R515A is not processed into gp120 and gp41 subunits of the Env glycoprotein and hence is not likely to induce toxic side effects due to release of soluble gp120. 2011 Virology Result HIV R515A;R515A;V513E 30;180;166 35;185;171 gp120;gp120;gp41;Env;Env;Gag 208;335;218;64;239;134 213;340;222;67;242;137 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. For this purpose, we infected Jurkat T cells with equal RT cpm of virus derived from HeLa cells transfected with different ratios of WT and Y164A/R515A mutant. 2011 Virology Result HIV R515A;Y164A 146;140 151;145 RT 56 58 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Having seen that the CTDel/R515A is partially restored in infectivity, we looked at its DN inhibitory potential in virus cell fusion assays. 2011 Virology Result HIV R515A 27 32 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. However, the R515A mutant displayed severely defective gp160 processing, as levels of gp120 were markedly reduced both in cell and viral lysates. 2011 Virology Result HIV R515A 13 18 gp120;gp160 86;55 91;60 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Interestingly, the Env/V513E mutant was more potent than Env/R515A in inhibiting WT Env mediated cell-to-cell fusion. 2011 Virology Result HIV R515A;V513E 61;23 66;28 Env;Env;Env 19;57;84 22;60;87 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Interestingly, the levels of virion-associated gp120 were also substantially reduced in cotransfections consisting of WT + R515A DNA. 2011 Virology Result HIV R515A 123 128 gp120 47 52 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. On the other hand, as expected, the R515A Env mutant showed punctuate PM Gag staining pattern suggesting that it had no effect on WT Gag membrane localization. 2011 Virology Result HIV R515A 36 41 Env;Gag;Gag 42;73;133 45;76;136 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Real time PCR for early reverse transcription products using env gene primers, showed that the R515A mutant was severely defective in initiation. 2011 Virology Result HIV R515A 95 100 RT;Env 24;61 45;64 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. S1, the 1GA Gag mutant was severely defective in PM localization as evident by diffuse cytosolic Gag staining as opposed to punctuate PM Gag staining pattern for WT Gag, while the CA mutants Q155N and Y164A showed lower, yet significant defects in membrane recruitment. 2011 Virology Result HIV Q155N;Y164A 191;201 196;206 Gag;Gag;Gag;Gag;Capsid 12;97;137;165;180 15;100;140;168;182 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. S3, all the DN Gag mutants but not Env mutant R515A were defective in virion release (as determined by released RT activity) but all the Gag and Env mutants were defective in virus infectivity (luciferase activity. 2011 Virology Result HIV R515A 46 51 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Since the R515A Env could only be minimally rescued with VSV-G, we speculated that defects in Gag/Env dissociation post-fusion may be responsible for the apparent post-entry defects. 2011 Virology Result HIV R515A 10 15 Env;Env;Gag 16;98;94 19;101;97 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Taken together, these findings suggest that the Env mutant R515A is multifunctional by affecting WT Env processing, cell-to-cell fusion and bystander apoptosis in addition to inhibiting virus infection. 2011 Virology Result HIV R515A 59 64 Env;Env 48;100 51;103 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. the 1:8, 1:16 and 1:32 Y164A/R515A: WT derived virus replicated with WT kinetics or better. 2011 Virology Result HIV R515A;Y164A 29;23 34;28 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The 1GA and the Q155N mutants also showed varying degrees of defects for early reverse transcription products but to a lesser extent. 2011 Virology Result HIV Q155N 16 21 RT 79 100 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The cytoplasmic tail partially contributes to the inhibitory effect of R515A Env. 2011 Virology Result HIV R515A 71 76 Env 77 80 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The Env mutant R515A affects gp160 processing, cell-to-cell fusion and apoptosis mediated by WT HIV Env. 2011 Virology Result HIV R515A 15 20 gp160;Env;Env 29;4;100 34;7;103 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The Env R515A mutant is severely defective in early stages of reverse transcription. 2011 Virology Result HIV R515A 8 13 RT;Env 62;4 83;7 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The fact that VSV-G complementation assays failed to rescue R515A virus suggests defects in a post-entry step, raising questions regarding the mechanism by which the R515A Env affects virus uncoating. 2011 Virology Result HIV R515A;R515A 60;166 65;171 Env 172 175 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The lentivirus Y164A/R515A inhibits HIV replication in MDMs derived from transduced stem cells. 2011 Virology Result HIV R515A;Y164A 21;15 26;20 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The transduction efficiency was ~19% and ~16% for the TyEFeGFP versus Y164A/R515A mutant respectively, as assessed by GFP and HIV p24 expression. 2011 Virology Result HIV R515A;Y164A 76;70 81;75 p24 130 133 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. These data suggest that the DN inhibitory effect of R515A Env is partially dependent on the cytoplasmic tail. 2011 Virology Result HIV R515A 52 57 Env 58 61 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. This could be due to the fact that incorporation of R515A inhibits bystander apoptosis thereby making more cells available for virus replication consistent with previous findings of. 2011 Virology Result HIV R515A 52 57 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. This is most likely due to the saturating anti-HIV activity of the Gag mutants Y164A and Q155N by themselves in our cotransfection assays. 2011 Virology Result HIV Q155N;Y164A 89;79 94;84 Gag 67 70 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. This phenomenon was more pronounced for the Y164A mutant compared to the 1GA and Q155N mutants. 2011 Virology Result HIV Q155N;Y164A 81;44 86;49 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. To test this, we constructed a tail-deleted version of HIV R515A (CTDel/R515A) and looked at its infectivity in TZM cells in the presence or absence of VSV-G. 2011 Virology Result HIV R515A;R515A 59;72 64;77 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. To this end, we chose the MA mutant 1GA, known to be defective in Gag plasma membrane binding and Q155N and Y164A mutations in the major homology region (MHR) of the HIV CA as potential candidates for DN HIV-1 inhibition. 2011 Virology Result HIV Q155N;Y164A 98;108 103;113 Gag;Matrix;Capsid 66;26;170 69;28;172 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. while HIV R515A and CTDel/R515A were severely impaired in infectivity assays in TZM cells, the infectivity of CTDel/R515A but not R515A alone could be rescued partially when complemented with VSV-G. 2011 Virology Result HIV R515A;R515A;R515A;R515A 10;26;116;130 15;31;121;135 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. With respect to the Env glycoprotein, we selected the cleavage-defective mutant R515A and the fusion-defective mutant V513E (the 41.2 mutant). 2011 Virology Result HIV R515A;V513E 80;118 85;123 Env 20 23 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. A significant number of sequences (15 to 12,361) were available for analysis in each subgroup, except for connection subdomain and RNase H domain of Q151M-containing subtype C sequences, in which there was only one sample sequenced beyond the DNA pol domain. 2011 Retrovirology Result HIV Q151M 149 154 Pol 247 250 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Accessory mutations in the DNA pol domain of RT have previously been demonstrated in the route to acquisition of Q151M MDR complex in subtype B viruses. 2011 Retrovirology Result HIV Q151M 113 118 Pol;RT 31;45 34;47 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. At most we observed a 1.3-fold change in susceptibility to d4T at 4 or 17 months leading us to conclude that Q151M is the main contributor to d4T resistance in the Q151M MDR complex. 2011 Retrovirology Result HIV Q151M;Q151M 109;164 114;169 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. C-terminal mutations are not associated with decreased susceptibility of Q151M-containing viruses to NRTIs in patient P66. 2011 Retrovirology Result HIV Q151M 73 78 NRTI 101 106 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Connection subdomain mutations in patient P66 partially restore replicative fitness of Q151M MDR-containing viruses. 2011 Retrovirology Result HIV Q151M 87 92 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Dynamics of emergence and genetic linkage of Q151M MDR complex mutations. 2011 Retrovirology Result HIV Q151M 45 50 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Genetic linkage analysis of the single genomes at 4, 17 and 37 months showed that the patient acquired the Q151M MDR mutations in the order: A62V, V75I and finally Q151M (Table 1). 2011 Retrovirology Result HIV A62V;Q151M;Q151M;V75I 141;107;164;147 145;112;169;151 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. However, the mutation was present in only one out of 33 single genomes at 17 months but none of the 31 single genomes at 37 months when the Q151M mutation emerged (Table 1). 2011 Retrovirology Result HIV Q151M 140 145 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. In addition, the analysis showed that drug resistance mutation T69N was genetically linked to Q151M MDR mutations and was acquired prior to Q151M. 2011 Retrovirology Result HIV Q151M;Q151M;T69N 94;140;63 99;145;67 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. In addition, the recombinant viruses expressing patient-derived RTs exhibited decreased susceptibilities to NRTIs FTC of >79-fold at 4 months and AZT of >15-fold at 37 months (Table 3) but remained susceptible to TDF even after the acquisition of the Q151M mutation at 37 months (Figure 3D) with no significant increases in IC50 values (P > 0.18). 2011 Retrovirology Result HIV Q151M 251 256 NRTI;RT 108;64 113;67 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. In contrast, two of these codon positions, namely 48 and 174, were not associated with the acquisition of Q151M in subtype B infected patients, but an additional two others were, namely 102 and 197 (P <= 0.029). 2011 Retrovirology Result HIV Q151M 106 111 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Interestingly, codon positions 386 and 403 in connection subdomain were also significantly associated with the acquisition of Q151M in subtype B infected individuals (P <= 0.018). 2011 Retrovirology Result HIV Q151M 126 131 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Intrapatient viral genetic diversity in the route to acquisition of Q151M MDR complex. 2011 Retrovirology Result HIV Q151M 68 73 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Next, we determined if the 20 accessory mutations that we identified in patient P66 were present in other patients who had developed resistance via the Q151M pathway. 2011 Retrovirology Result HIV Q151M 152 157 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Of note, the N348I mutation was identified in the connection subdomain of all single genomes at 4 months. 2011 Retrovirology Result HIV N348I 13 18 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Similarly, the coevolved C-terminal region did not contribute to 3TC resistance, including the previously identified N348I mutation at 4 months, neither did they contribute to the decreases in susceptibility to ABC, ddI or FTC (Figure 3C and 3D and Table 3). 2011 Retrovirology Result HIV N348I 117 122 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The correlation between the progressive increments in the frequency of these mutations and the sequential acquisition of the Q151M MDR mutations suggested that they could be facilitating the emergence of the Q151M MDR complex. 2011 Retrovirology Result HIV Q151M;Q151M 125;208 130;213 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The decrease in NVP susceptibility associated with the C-terminal domain at 4 months is likely due to the presence of the N348I mutation in the connection subdomain which disappears at later time points. 2011 Retrovirology Result HIV N348I 122 127 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The effect on susceptibility to 3TC was probably due to M184I/V mutations which were seen by 4 months. 2011 Retrovirology Result HIV M184I;M184V 56;56 63;63 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The emergence and presence of mutations in DNA pol domain, connection subdomain and RNase H domain were assessed by SGS, and their genetic linkage to Q151M MDR mutations was determined. 2011 Retrovirology Result HIV Q151M 150 155 Pol 47 50 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The emergence of Q151M after the secondary mutations A62V and V75I is rare. 2011 Retrovirology Result HIV A62V;Q151M;V75I 53;17;62 57;22;66 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The patient-derived RT at 4 months had already developed the M184I mutation which is known to affect viral replicative fitness. 2011 Retrovirology Result HIV M184I 61 66 RT 20 22 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The patient-derived RT exhibited a 23-fold increase in 3TC IC50 values at 4 months which did not increase at 17 and 37 months despite the acquisition of the Q151M MDR mutations (Table 3). 2011 Retrovirology Result HIV Q151M 157 162 RT 20 22 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The patient-derived RTs remained d4T-susceptible until the development of the Q151M mutation at 37 months, when there was a significant increase (~16-fold) in IC50 values compared to wild-type RT (Figure 3B; P < 0.002). 2011 Retrovirology Result HIV Q151M 78 83 RT;RT 20;193 23;195 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The Q151M MDR mutations were also genetically linked to NRTI mutations M184IV and L210F, and NNRTI mutations E138A, Y181I and H221Y (Table 1). 2011 Retrovirology Result HIV E138A;H221Y;L210F;M184I;M184V;Q151M;Y181I 109;126;82;71;71;4;116 114;131;87;77;77;9;121 NNRTI;NRTI 93;56 98;60 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The susceptibility to TDF could probably be influenced by the presence of M184V which has been shown to increase HIV-1 sensitivity to TDF. 2011 Retrovirology Result HIV M184V 74 79 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The virus expressing the full-length patient-derived RT containing the Q151M mutation at 37 months demonstrated ~42% replicative capacity of full-length patient-derived RT at 4 months (P < 0.0001; Figure 2E). 2011 Retrovirology Result HIV Q151M 71 76 RT;RT 53;169 55;171 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. These data indicate that some of the accessory mutations identified in the DNA pol domain and connection subdomain of patient P66 are highly prevalent in patients who develop resistance through the Q151M pathway and that they could be playing an important role in the acquisition of the Q151M MDR. 2011 Retrovirology Result HIV Q151M;Q151M 198;287 203;292 Pol 79 82 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. This indicates that the identified accessory mutations could be playing an important role in the evolution and development of the Q151M MDR. 2011 Retrovirology Result HIV Q151M 130 135 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. This showed that eight out of the 12 codon positions identified in the DNA pol domain of patient P66 were significantly associated with the sequences containing the Q151M mutation compared to RTI-treatment naive sequences. 2011 Retrovirology Result HIV Q151M 165 170 Pol;RT 75;192 78;195 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. This suggests a serial founder effect in the development of Q151M MDR. 2011 Retrovirology Result HIV Q151M 60 65 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. This suggests that the Q151M mutation, as well as being the main determinant of drug resistance in the Q151M MDR complex, also has a more significant effect on virus replication fitness that is partially restored by mutations in the connection subdomain. 2011 Retrovirology Result HIV Q151M;Q151M 23;103 28;108 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Thus, unlike d4T the cumulative acquisition of mutations on the route to Q151M MDR complex results in a parallel cumulative decrease in susceptibilities to ABC and ddI. 2011 Retrovirology Result HIV Q151M 73 78 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. We compared mutation frequencies in subtype B or C samples from RTI-treatment naive patients and Q151M-containing patient samples on the Stanford University HIV drug resistance database. 2011 Retrovirology Result HIV Q151M 97 102 RT 64 67 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. We initially determined the development of Q151M MDR complex using SGS of full-length RT gene in the four sequential samples collected from patient P66 at 4, 17, 28 and 37 months. 2011 Retrovirology Result HIV Q151M 43 48 RT 86 88 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. We investigated the emergence of the Q151M MDR complex in one of the two patients in the CHAP2 cohort study who had developed resistance via the Q151M pathway. 2011 Retrovirology Result HIV Q151M;Q151M 37;145 42;150 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. We, therefore, determined whether accessory mutations developed in this subtype C HIV-1 virus and whether the C-terminal region of RT played a role in the emergence of the Q151M MDR complex. 2011 Retrovirology Result HIV Q151M 172 177 RT 131 133 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Among them, 17 had a prevalence > 10% in X4-predicted viruses (the known S11KR and E25KRQ, and I12V, H13ST, A19V, F20VY, Y21H, I27TV, Q32KR, H34Y), suggesting that within the V3 region, many more mutations are associated with CXCR4 usage (Figure 1a). 2011 Retrovirology Result HIV A19V;E25K;E25Q;E25R;F20V;F20Y;H13S;H13T;H34Y;I12V;I27T;I27V;Q32K;Q32R;S11K;S11R;Y21H 108;83;83;83;114;114;101;101;141;95;127;127;134;134;73;73;121 112;89;89;89;119;119;106;106;145;99;132;132;139;139;78;78;125 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Among them, 5 mutations had a prevalence > 10% in X4-predicted viruses (V69I, A96T, S129N, D163N and A189S) (Figure 1b). 2011 Retrovirology Result HIV A189S;A96T;D163N;S129N;V69I 101;78;91;84;72 106;82;96;89;76 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. An exception was represented by the A96Ngp41 mutation that was positively correlated with T22AV3 (phi = 0.22; P = 0.030; both associated with CCR5-usage) and negatively correlated with the known S11KR mutations (phi = -0.17; P = 0.018). 2011 Retrovirology Result HIV S11K;S11R 195;195 200;200 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. As a first analysis, we confirmed in our dataset that the classical V3 positions 11 and 25 (consistent with previous observations), wild-type amino acid at position 11, S11S, and E25D mutation were significantly associated with R5-tropic viruses, while mutations S11KR and E25KRQ were significantly associated with CXCR4 co-receptor usage (Figure 1a). 2011 Retrovirology Result HIV E25D;E25K;E25Q;E25R;S11K;S11R;S11S 179;273;273;273;263;263;169 183;279;279;279;268;268;173 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Beyond these mutations, the wild type amino acid at 13 gp41 positions were also significantly associated with the R5-prediction (Q52Q, N126N, L134L, Q142Q, D153D, L181L, V190V, F206F, A212A, R250R, E280E, N287N and G314G) (Figure 1b). 2011 Retrovirology Result HIV A212A;D153D;E280E;F206F;G314G;L134L;L181L;N126N;N287N;Q142Q;Q52Q;R250R;V190V 184;156;198;177;215;142;163;135;205;149;129;191;170 189;161;203;182;220;147;168;140;210;154;133;196;175 gp41 55 59 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Consequently, we could speculate that gp41 A30T, L34M, A96NT, S129DQN, N140IT, N195K and L210P mutations may act together (directly or indirectly) with specific V3 signatures, via allosteric effects on the gp120/gp41 complex. 2011 Retrovirology Result HIV A96N;A96T;L210P;L34M;N140I;N140T;N195K;S129D;S129N;S129Q 55;55;89;49;71;71;79;62;62;62 60;60;94;53;77;77;84;69;69;69 gp120;gp41;gp41 206;38;212 211;42;216 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. In our dataset, the mutation N7K has been found only in X4-predicted viruses (prevalence 9.5%; P = 0.002) (Figure 1a). 2011 Retrovirology Result HIV N7K 29 32 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. In our study, these 2 mutations, A30T and L34M, were both 100% associated to CXCR4-tropic viruses (Table 1). 2011 Retrovirology Result HIV A30T;L34M 33;42 37;46 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. In particular, the topology of the dendrogram suggests the existence of a cluster associated with R5-usage and involving S11S, E25D, and T22A in the V3 and A96N and S129DQ in gp41 (bootstrap = 0.88) (Figure 2). 2011 Retrovirology Result HIV A96N;E25D;S11S;S129D;S129Q;T22A 156;127;121;165;165;137 160;131;125;171;171;141 gp41 175 179 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. In particular, we identified 13 gp41 mutations whose prevalence was significantly higher in R5-using than in X4-using viruses: 7 of them had a prevalence > 10% in R5-predicted viruses (A69N, E110K, S129D, R209L, F241L, V267A, and I270T). 2011 Retrovirology Result HIV A69N;E110K;F241L;I270T;R209L;S129D;V267A 185;191;212;230;205;198;219 189;196;217;235;210;203;224 gp41 32 36 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. In this work, it has been shown that mutations at N-terminus of gp41, such as A30T and L34M, are strongly associated with co-receptor phenotype in two independent datasets (444 and 1916 patients screened, respectively). 2011 Retrovirology Result HIV A30T;L34M 78;87 82;91 gp41 64 68 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Indeed, Huang et colleagues have shown that mutations in the fusion peptide and cytoplasmic tail of gp41 contribute to CXCR4 use by a dual-tropic clone, while a single G515V mutation (according to HXB2 gp140 numbering) in gp41-fusion-peptide of another dual-tropic clone was sufficient to confer CXCR4 use to the R5-tropic original clone. 2011 Retrovirology Result HIV G515V 168 173 gp140;gp41;gp41 202;100;222 207;104;226 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Moreover, the novel identified V3 mutations T22A in the R5-predicted viruses, and I12V, A19V, Y21H and H34Y in the X4-predicted viruses were also confirmed (P < 0.05). 2011 Retrovirology Result HIV A19V;H34Y;I12V;T22A;Y21H 88;103;82;44;94 92;107;86;48;98 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Seven of them had a prevalence > 10% in R5-predicted viruses (the known E25D, and H13P, G15A, R18Q, F20L, Y21F and T22A). 2011 Retrovirology Result HIV E25D;F20L;G15A;H13P;R18Q;T22A;Y21F 72;100;88;82;94;115;106 76;104;92;86;98;119;110 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. Similarly, S129DQgp41, associated with CCR5-usage and localized in the gp41 HR2 domain, established negative correlation with the S11KR, strongly associated with CXCR4-usage, (phi = -0.21; P = 0.041) (Table 1). 2011 Retrovirology Result HIV S11K;S11R 130;130 135;135 gp41 71 75 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. The classical R5-tropic determinants S11S and E25D were found with high prevalence in NSI-sequences (73.6% and 64.1%, respectively, versus 34% and 11%, respectively, in SI-sequences; P < 0.05), while the classical X4-tropic mutations S11KR and E25KRQ were found with high prevalence in SI-sequences (40.6% and 51.6%, respectively, versus 2% and 11%, respectively, in NSI-sequences; P < 0.05). 2011 Retrovirology Result HIV E25D;E25K;E25Q;E25R;S11K;S11R;S11S 46;244;244;244;234;234;37 50;250;250;250;239;239;41 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. This involves the V3 mutations T8I, S11KR, F20IVY, G24EKR, E25KQR, Q32KR along with the gp41 mutations A30T, A189S, N195K, L210P (bootstrap = 0.84) (Figure 2). 2011 Retrovirology Result HIV A189S;A30T;E25K;E25Q;E25R;F20I;F20V;F20Y;G24E;G24K;G24R;L210P;N195K;Q32K;Q32R;S11K;S11R;T8I 109;103;59;59;59;43;43;43;51;51;51;123;116;67;67;36;36;31 114;107;65;65;65;49;49;49;57;57;57;128;121;72;72;41;41;34 gp41 88 92 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. As with 902, a majority of the cells expressing the Y712C-containing mutants exhibited much higher levels of surface staining with b12 and 2G12, although the absolute increase differed (approximately 8 and 10-fold for Y, respectively). 2011 Retrovirology Result HIV Y712C 52 57 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. By inserting the Y712C mutation into WT Env, the MFI Index value of the Y mutant increased to 447% of WT. 2011 Retrovirology Result HIV Y712C 17 22 Env 40 43 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Direct comparison of the two panels indicates that the Y712C mutation did not affect the fusogenicity of the Env mutants in the context of cell-cell fusion, with the Y mutant maintaining 96% fusion activity compared to WT. 2011 Retrovirology Result HIV Y712C 55 60 Env 109 112 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. In each case, cells expressing the YE mutant showed the smallest increase in Env surface expression of the Y712C-containing mutants relative to WT. 2011 Retrovirology Result HIV Y712C 107 112 Env 77 80 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. In Figure 3, the Env mutants have been separated into two series, those containing the WT Y712 motif and those containing the Y712C mutation. 2011 Retrovirology Result HIV Y712C 126 131 Env 17 20 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. In Figure 4A, the flow cytometry dot plots of mAb 902 stained cells reveal a distinct shift in the staining pattern between the WT Y712 panels and the Y712C panels, with a greater proportion of the cells staining and with higher intensity in the latter, consistent with increased levels of surface expression. 2011 Retrovirology Result HIV Y712C 151 156 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Introduction of the L765H/Y768S mutations into the env sequence generated mutant A. 2011 Retrovirology Result HIV L765H;Y768S 20;26 25;31 Env 51 54 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Introduction of the Y712C mutation to WT and the Env mutants A, B, C, D, and E resulted in the generation of the Y, YA, YB, YC, YD, and YE mutants. 2011 Retrovirology Result HIV Y712C 20 25 Env 49 52 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Meanwhile, the mutant S2 (Y768S) exhibited only 45% WT efficiency of virus entry. 2011 Retrovirology Result HIV Y768S 26 31 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Mutagenesis of the first two pins (L765H and Y768S) in the three-pin motif LxxY768xxL, which binds to AP2, at the N-terminus of LLP2 resulted in 62% and 63% the fusogenicity of WT for mutants A and YA, respectively. 2011 Retrovirology Result HIV L765H;Y768S 35;45 41;50 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Mutations in S1 (L765H), S2 (Y768S), S3 (LLLI774SHSN), and S4 (LL784HQ) are located in the N-terminus (S1, S2), middle (S3) and C-terminus (S4) of the LLP2 motif. 2011 Retrovirology Result HIV L765H;Y768S 17;29 22;34 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Once again, the samples have been separated into two series: those containing the WT Y712 motif and those containing the Y712C mutation. 2011 Retrovirology Result HIV Y712C 121 126 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Subsequent mutagenesis of the third pin (L771S) and the LL774LI776 motifs resulted in a significant decrease in fusion compared to WT, with B and YB reducing fusogenicity to 41% and 35% of WT respectively. 2011 Retrovirology Result HIV L771S 41 46 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The addition of the Y712C mutation facilitated gp41 incorporation in mutant YB and YC, compared to their non-Y712C counterparts, while mutants YD and YE showed similar gp41 levels to their non-Y712 counterparts. 2011 Retrovirology Result HIV Y712C;Y712C 20;109 25;114 gp41;gp41 47;168 51;172 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The integrity of the LLP2 motif appeared most important for Env fusogenicity since mutants S2 (Y768S) and S3 (LLLI774SHSN) retained the lowest level of cell-cell fusogenicity, 64.7% and 67.8% of WT, respectively. 2011 Retrovirology Result HIV Y768S 95 100 Env 60 63 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The loss of hydrophobicity in mutants S1 (L765H), S3 (LLLI774SHSN), and S4 (LL784HQ) significantly reduced the single-round viral infection to 66.5%, 16.6%, and 59.2% of WT. 2011 Retrovirology Result HIV L765H 42 47 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The results indicate that all of the Env CD mutants maintained at least WT levels of surface expression, while introduction of the Y712C mutation into the CD resulted in an increase in glycoprotein cell surface expression, following immunostaining with all three antibodies. 2011 Retrovirology Result HIV Y712C 131 136 Env 37 40 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The staining patterns for both antibodies are similar to that observed with mAb 902, with a majority of the Y712WT mutant-expressing cells exhibiting MFI indices similar to WT Env, although for 2G12 a 3-4-fold increase in surface staining was observed for mutants B-E. 2011 Retrovirology Result HIV Y712T;Y712W 108;108 114;114 Env 176 179 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The subsequent addition of L771S/LLLI774SHSN to mutant A results in mutant B, the addition of LL784HQ to mutant B results in mutant C, the additional changes of Y795S/LL799HQ/Y802S to mutant C produce mutant D, and LL814AA/LL855AA was combined with mutant D to create mutant E. 2011 Retrovirology Result HIV Y795S;Y802S;L771S 161;175;27 166;180;32 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The Y712C mutation reduced the level of gp120 and gp41 incorporation to 49% and 73% that of WT, respectively. 2011 Retrovirology Result HIV Y712C 4 9 gp120;gp41 40;50 45;54 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. This increase was reflected in the MFI Index values of the other mutants containing the Y712C, including YA at 563%, YB at 396%, YC at 563%, YD at 409%, and YE at 194%. 2011 Retrovirology Result HIV Y712C 88 93 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. While the Y712C substitution in mutant Y had little effect on cell-cell fusion, the infectivity of viruses pseudotyped with this Env was 47% that of WT, and the remaining Y712C-containing mutants were reduced in virus entry by more than 94% compared to WT. 2011 Retrovirology Result HIV Y712C;Y712C 10;171 15;176 Env 129 132 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Cellular depletion of CD4 bearing thymocytes which is indicative of viral pathogenesis, primarily in the CD4+CD8+ population, was observed in mice infected with wild type HIV-1 NL4-3 and the M184V containing strains within 5 weeks following infection. 2010 The open medical informatics journal Result HIV M184V 191 196 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. HIV-1NL4-3 wild type, HIV-1NL4-3 with the D30N mutation, HIV-1NL4-3 with the M184V mutation, and HIV-1NL4-3 containing both the D30N and M184V mutations all had a titer of 300 picograms per infectious unit, indicating that the presence of the mutation in the drug resistant viruses did not affect initial viral infectivity. 2010 The open medical informatics journal Result HIV D30N;D30N;M184V;M184V 42;128;77;137 46;132;82;142 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. In fact, mice infected with strains containing the D30N mutation (including the double mutant) were not statistically different from the mock infected mice in terms of percent total CD4+ thymocytes. 2010 The open medical informatics journal Result HIV D30N 51 55 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Infection of mice with HIV-1NL4-3 containing the M184V mutation produced similar viral kinetics as the wild type virus. 2010 The open medical informatics journal Result HIV M184V 49 54 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Mice harboring HIV-1NL4-3 containing the D30N mutant strains had significantly lower levels of HIV RNA than the wildtype or M184V alone groups (P=0.001). 2010 The open medical informatics journal Result HIV D30N;M184V 41;124 45;129 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Mice infected with HIV-1NL4-3 containing the D30N or D30N+M184V mutation, however, had barely detectable viral DNA at all three time points. 2010 The open medical informatics journal Result HIV D30N;D30N;M184V 45;53;58 49;57;63 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Mice infected with the M184V mutation alone had a profound depletion in thymocytes compared to mock infected mice (p=0.027) and was not significantly different from the depletion found in mice infected with wildtype virus, indicating that the D30N is primarily responsible for the attenuated virulence. 2010 The open medical informatics journal Result HIV D30N;M184V 243;23 247;28 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Seven weeks post inoculation, we found profound CD4+ thymocyte depletion in the mice infected with wild-type virus or the virus containing the M184V mutation alone. 2010 The open medical informatics journal Result HIV M184V 143 148 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The average cumulative area under the curve was not significantly different for M184V versus wildtype. 2010 The open medical informatics journal Result HIV M184V 80 85 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The differences in percent total thymocytes between mock and the two D30N groups were not significant at any time point (even without adjusting for multiple comparisons). 2010 The open medical informatics journal Result HIV D30N 69 73 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The level of depletion in these two groups was significantly greater than the level of depletion found in mice infected with strains that included the D30N mutation (p=0.001). 2010 The open medical informatics journal Result HIV D30N 151 155 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The model found that the D30N mutation had the largest decrease in RC relative to other resistance-associated mutations suggesting that this mutation may have clinical benefit in prolonging disease progression by conferring a RC defect. 2010 The open medical informatics journal Result HIV D30N 25 29 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. There was no statistically significant difference in HIV DNA levels between the D30N and the D30N+M184V infected group at any time point. 2010 The open medical informatics journal Result HIV D30N;D30N;M184V 80;93;98 84;97;103 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Thy/liv implants were initially infected with equivalent amounts of infectious units of wild type, D30N-containing, M184V-containing, and both D30N and M184V containing HIV-1NL4-3 in parallel and the effects of the virus were examined at 3, 5, and 7 weeks following infection. 2010 The open medical informatics journal Result HIV D30N;D30N;M184V;M184V 99;143;116;152 103;147;121;157 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. To assess the effects the in silico identified D30N PR and the previously implicated M184V RT mutation in infectivity of HIV-1 we assessed viral titers of molecularly clones variants of HIV-1NL4-3 containing these mutations in a standard limiting dilution assay. 2010 The open medical informatics journal Result HIV D30N;M184V 47;85 51;90 PR;RT 52;91 54;93 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. We found that the virus containing the M184V mutation displayed slightly delayed replication kinetics while the viruses containing the D30N alone and in combination with M184V and the double mutant had a more dramatic decrease in viral replication as compared to the wild-type virus. 2010 The open medical informatics journal Result HIV D30N;M184V;M184V 135;39;170 139;44;175 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. All of the samples positive for K103N by population sequencing were similarly positive by AS-PCR, with a median quantitative value of 87.8% (IQR, 54.3-99.5), whereas for the samples only positive on AS-PCR it was 1.1% (IQR, 0.6-5.0) (Figure 2). 2011 AIDS (London, England) Result HIV K103N 32 37 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. An additional sample with an unusual K103T polymorphism had a quantitative AS-PCR value of 0.9 for K103N. 2011 AIDS (London, England) Result HIV K103N;K103T 99;37 104;42 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. As expected, NNRTI mutations were most prevalent and were present in 27% (69/255) of samples: 20% had Y181C and 5% K103N (Figure 1). 2011 AIDS (London, England) Result HIV K103N;Y181C 115;102 120;107 NNRTI 13 18 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Detection of Y181C and K103N minority populations by AS-PCR. 2011 AIDS (London, England) Result HIV K103N;Y181C 23;13 28;18 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. However analysis of the K103N mutation showed that there was a significant decline with age that was particularly apparent in the first 6 months suggesting that minority K103N variants do not persist as long as Y181C in infants. 2011 AIDS (London, England) Result HIV K103N;K103N;Y181C 24;170;211 29;175;216 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Interestingly, the ratio of all Y181C-containing samples detected only by population sequencing relative to those detected by either method (52/77, 68%) was significantly higher than the ratio of all K103N-containing samples detected only by population sequencing (13/34, 38.2%), p=0.006. 2011 AIDS (London, England) Result HIV K103N;Y181C 200;32 205;37 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Nineteen samples had major NRTI mutations, specifically K219E/Q (n=8), L74V (n=7), K70E (n=3), D67N (n=2) and L210W (n=1). 2011 AIDS (London, England) Result HIV D67N;K219E;K219Q;K70E;L210W;L74V 95;56;56;83;110;71 99;63;63;87;115;75 NRTI 27 31 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. NNRTI minor mutations were also detected, specifically E138A (n=20), V179D (n=7), V90I (n=3) and A98G (n=1), as well as the NNRTI-associated polymorphisms K101Q/T (n=3), E138G/S (n=3), V179A (n=2), H221Y (n=2) and L234P (n=1). 2011 AIDS (London, England) Result HIV A98G;E138A;E138G;E138S;H221Y;K101Q;K101T;L234P;V179A;V179D;V90I 97;55;170;170;198;155;155;214;185;69;82 101;60;177;177;203;162;162;219;190;74;86 NNRTI;NNRTI 0;124 5;129 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. No samples had both K103N and Y181C detected by population sequence, and only 12 (4.7%) had both mutations detected by either method. 2011 AIDS (London, England) Result HIV K103N;Y181C 20;30 25;35 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Of the 5 samples that were positive for AS-PCR 18-24 months post-exposure to sdNVP but wild-type by sequencing, 3 were Y181C positive and 2 were K103N positive. 2011 AIDS (London, England) Result HIV K103N;Y181C 145;119 150;124 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. One sample had both K103N and Y188C by population genotype, otherwise multiple major NNRTI mutations were not found. 2011 AIDS (London, England) Result HIV K103N;Y188C 20;30 25;35 NNRTI 85 90 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Other major NNRTI mutations V106M, Y188C and G190A were found in a small proportion of infants under 12 months but were absent in older children. 2011 AIDS (London, England) Result HIV G190A;V106M;Y188C 45;28;35 50;33;40 NNRTI 12 17 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Other NRTI-associated mutations detected included T69A/N/S (n=21), V75L, V118I and T215A/I. 2011 AIDS (London, England) Result HIV T215A;T215I;T69A;T69N;T69S;V118I;V75L 83;83;50;50;50;73;67 90;90;58;58;58;78;71 NRTI 6 10 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Similar to K103R, this polymorphism falls out of the primer binding region and thus the low positive AS-PCR value was assumed to reflect the presence of K103N. 2011 AIDS (London, England) Result HIV K103N;K103R 153;11 158;16 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Specifically 8 samples were positive for Y181C by population sequence and K103N by AS-PCR, 2 samples were positive for K103N by population sequence and Y181C by AS-PCR, and 2 samples were positive for both mutations by AS-PCR. 2011 AIDS (London, England) Result HIV K103N;K103N;Y181C;Y181C 74;119;41;152 79;124;46;157 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The G190A and Y188C mutations were each detected in 2 samples and V106I/M in 1 sample. 2011 AIDS (London, England) Result HIV G190A;V106I;V106M;Y188C 4;66;66;14 9;73;73;19 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The K103N mutation was detected in an additional 8% (21/255) of samples by AS-PCR. 2011 AIDS (London, England) Result HIV K103N 4 9 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The major PI mutations M46I/L and I47V were present in 4 samples, and minor PI mutations L10I/V, V11I, A71T, I85V, and N88D were also detected. 2011 AIDS (London, England) Result HIV A71T;I47V;I85V;L10I;L10V;M46I;M46L;N88D;V11I 103;34;109;89;89;23;23;119;97 107;38;113;95;95;29;29;123;101 PI;PI 10;76 12;78 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The PI mutation T74S was found in 29 samples, and 1 sample had an insertion at position 35 in protease. 2011 AIDS (London, England) Result HIV T74S 16 20 PR;PI 94;4 102;6 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The polymorphism K103R was detected by population sequencing in 4 samples, and did not appear to affect the assay in that all 4 samples were negative by AS-PCR. 2011 AIDS (London, England) Result HIV K103R 17 22 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The Y181C mutation was detected by AS-PCR in all 52 samples that were positive by sequencing as well as an additional 10% (25/250) that were wild-type by sequencing. 2011 AIDS (London, England) Result HIV Y181C 4 9 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The Y181C mutation was most common at all time-points and only Y181C and K103N persisted until 18 months. 2011 AIDS (London, England) Result HIV K103N;Y181C;Y181C 73;4;63 78;9;68 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. This indicates that K103N occurred mostly as a minority species and hence the K103N AS-PCR was particularly useful at revealing additional samples harboring this mutation. 2011 AIDS (London, England) Result HIV K103N;K103N 20;78 25;83 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Two samples had the polymorphisms Y181F/S in the primer binding regions which interfered with the AS-PCR assay giving false positive results, and were excluded from analysis. 2011 AIDS (London, England) Result HIV Y181F;Y181S 34;34 41;41 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. 10) the development of Y181C preceded the emergence of K103N. 2011 PloS one Result HIV K103N;Y181C 55;23 60;28 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. 19), the drug-resistant HIV-1 variant (100% Y181C) which had emerged early at week 1 persisted throughout the whole observation period and was still present at month 12 (18-month sample was missing). 2011 PloS one Result HIV Y181C 44 49 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. 9), the resistant virus population being 10% (Y181C) at month 3 was not detectable at month 6 and month 15 but re-emerged and constituted the majority of the HIV-1 population at month 18; this woman was infected with subtype C and had started NVP-containing ART 6 months after NVP-SD intake. 2011 PloS one Result HIV Y181C 46 51 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. 9/18 (50%) women with resistance formation exhibited the K103N and the Y181C mutation in their viral population. 2011 PloS one Result HIV K103N;Y181C 57;71 62;76 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. In the remaining 9/18 women with resistance formation the resistant virus carried either the K103N (n = 7) or the Y181C (n = 2) mutation during the observation period. 2011 PloS one Result HIV K103N;Y181C 93;114 98;119 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. Whenever population-based sequencing detected HIV-1 variants carrying the K103N and/or Y181C mutation, the ASPCR assays indicated the presence of these mutations as well. 2011 PloS one Result HIV K103N;Y181C 74;87 79;92 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. A comparison of primer and template sequences shows that similar mechanisms of primer/template misalignment, slippage and dislocation are the likely cause of the elevated rates of K65R with the subtype C template (Figure 3C). 2011 PloS one Result HIV K65R 180 184 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. All of the transcripts that resulted from dislocation and subsequent realignment contained K65R. 2011 PloS one Result HIV K65R 91 95 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. As stated, the 0MM1 primers did not contain a mutagenic nt at the 3' position and dGTP was the only nt provided to ensure production of K65R-containing transcripts. 2011 PloS one Result HIV K65R 136 140 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. As with the primer-dependent assays, the different purification activities of the enzymes used are likely contributors to the relatively minor differences in K65R-transcript production when subtype B RT is directly compared to subtype C RT. 2011 PloS one Result HIV K65R 158 162 RT;RT 200;237 202;239 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Dislocation specificity and generation of K65K, K65T and K65I. 2011 PloS one Result HIV K65I;K65K;K65T 57;42;48 61;46;52 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. However, DNA synthesis did not occur as quickly as with synthesis of K65K because a mismatch was required for DNA synthesis to proceed beyond the +1 position on the template. 2011 PloS one Result HIV K65K 69 73 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Importantly, K65R and K65N are the only known N(t)RTI resistance-associated mutations at codon 65 of RT. 2011 PloS one Result HIV K65N;K65R 22;13 26;17 NRTI;RT 46;101 53;103 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In contradistinction to the major differences obtained between the use of templates of subtype B or C origin in formation of K65R transcripts, the relatively minor differences obtained with subtype B vs. 2011 PloS one Result HIV K65R 125 129 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In the primer-independent reaction, dislocation that occurs with realignment yields a 2 nt product at the P+2nt position that contains intact K65R transcripts (Figure 8D). 2011 PloS one Result HIV K65R 142 146 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. K65T and K65I are very rare and viruses harboring either of these mutations remain fully susceptible to N(t)RTIs and NNRTIs. 2011 PloS one Result HIV K65I;K65T 9;0 13;4 NRTI;NNRTI 104;117 112;123 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. K65T production was next evaluated with the addition of a C at the 3'-end of the primer with BWT RT on both the subtype B and C templates (Figure 9B). 2011 PloS one Result HIV K65T 0 4 RT 97 99 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Nearly identical patterns to the BWT RT-mediated DNA synthesis were obtained with CWT RT for each of K65K (Figure S3A), K65T (Figure S3B), and K65I (Figure S3C). 2011 PloS one Result HIV K65I;K65K;K65T 143;101;120 147;105;124 RT;RT 37;86 39;88 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Over time, production of P+1nt products seems to level off as a result of realignment to form additional P+2nt products that contain the K65R mutation. 2011 PloS one Result HIV K65R 137 141 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Primer-dependent generation of K65R and template dislocation. 2011 PloS one Result HIV K65R 31 35 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Primer-independent K65R production and template dislocation. 2011 PloS one Result HIV K65R 19 23 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Similarly, production of K65I, resulting from the presence of a T at the 3'-end of the primer, was similar for both templates, without any evidence of dislocation (Figure 9C). 2011 PloS one Result HIV K65I 25 29 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Subtype B and C RT Sequence Analysis and Generation of K65R. 2011 PloS one Result HIV K65R 55 59 RT 16 18 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The 13 nt product formed more slowly than was the case for K65K due to the nt mismatch between the primer and template strands. 2011 PloS one Result HIV K65K 59 63 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The former did not show significant differences in regard to K65R mutagenesis. 2011 PloS one Result HIV K65R 61 65 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The levels of pre and post-realignment products following dislocation can shed light on the proportion of transcripts that contain the K65R mutation or that harbor a -1 frameshift mutation during primer-dependent transcription from the subtype C template. 2011 PloS one Result HIV K65R 135 139 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. This suggests that non-realigned products (P+1nt products) might eventually realign to produce more K65R-containing transcripts (P+2nt products). 2011 PloS one Result HIV K65R 100 104 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Thus, misalignment would result in dislocation to produce either transcripts with a -1 nt frameshift mutation (FL-1nt band) or, upon subsequent primer/template realignment, transcripts containing the K65R mutation (FL band). 2011 PloS one Result HIV K65R 200 204 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. To ensure the template-specific and enzyme-independent nature of both K65R production and primer/template dislocation on the subtype C template, similar experiments were performed using wild-type subtype C (CWT) RT. 2011 PloS one Result HIV K65R 70 74 RT 212 214 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. We first evaluated wild-type K65K production by using an A base at the 3'-end of the primer with BWT RT on both the subtype B and C templates. 2011 PloS one Result HIV K65K 29 33 RT 101 103 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. When comparing the subtype B and C primers and templates in the primer-independent setting, dislocation occurred only with the subtype C template at the exact location of K65R-development (Figure 4C), probably because the dislocation allowed the primer and template to misalign, permitting dGTP to correctly bind opposite the C to yield the P+1nt product. 2011 PloS one Result HIV K65R 171 175 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. With the subtype B template, no pausing was seen and a distinct, 13 nt DNA product band containing K65R was observed at the full-length (FL) position. 2011 PloS one Result HIV K65R 99 103 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Among the 46 ARV-resistant patients, 25 also harboured the M184V mutation conferring resistance to 3TC/FTC; among them, eight patients were also resistant to the other NRTI drug in their regimen because of the high number of TAMs (n = 4), or the presence of the Q151M (n = 1) or the K65R (n = 3) mutation. 2011 Journal of the International AIDS Society Result HIV K65R;M184V;Q151M 283;59;262 287;64;267 NRTI 168 172 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Importantly, eight patients were already predicted to be resistant to etravirine, the new NNRTI, either because they harboured the single Y181V mutation (n = 3) or due to the presence of both Y181C and H221Y mutations (n = 5). 2011 Journal of the International AIDS Society Result HIV H221Y;Y181C;Y181V 202;192;138 207;197;143 NNRTI 90 95 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. In seven patients, the presence of one or two NRTI mutations (M41L, D67N) was also seen, but this had not yet resulted in drug resistance. 2011 Journal of the International AIDS Society Result HIV D67N;M41L 68;62 72;66 NRTI 46 50 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. The presence of the K65R also means that tenofovir (TDF) will not be effective when used in the second-line regime, and the Q151M mutation commonly confers multi-drug resistance to NRTIs (AZT, ABC, ddI and d4T). 2011 Journal of the International AIDS Society Result HIV K65R;Q151M 20;124 24;129 NRTI 181 186 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Two patients had virus mutations indicative of the TAM-1 profile (M41L, L210W, T215S), and two of the TAM-2 profile (D67N, K70R, T215F, K219Q/R/E). 2011 Journal of the International AIDS Society Result HIV D67N;K219E;K219Q;K219R;K70R;L210W;M41L;T215F;T215S 117;136;136;136;123;72;66;129;79 121;145;145;145;127;77;70;134;84 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. V106A/M, K101E and Y188C/L were noted in four, three and two patients, respectively. 2011 Journal of the International AIDS Society Result HIV K101E;V106M;Y188C;Y188L;V106A 9;0;19;19;0 14;7;26;26;7 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. DRM to both NRTI and NNRTI were found in 11/36 (30.5%) of EFV recipients, with the combination of M184V and K103N being most prevalent. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;M184V 108;98 113;103 NNRTI;NRTI 21;12 26;16 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. Four participants had at least one thymidine-associated mutation (TAM) - two recipients of ZDV+ddI had D67N + K70R, another ZDV+ddI recipient had K70R alone. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV D67N;K70R;K70R 103;110;146 107;114;150 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. K103N was the most commonly detected in 9 (25%) participants, V106M in 6 (16.7%), and G190S/A +/- Y188C/L in 6 (16.7%). 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;G190S;V106M;Y188C;Y188L;K103N 86;86;62;98;98;0 93;93;67;105;105;5 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. No Y181C mutation was detected. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 3 8 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. Of the 32 individuals who never received EFV, 6 (18.8%, CI: 7.2-36.4%) had NRTI-associated mutations; five had M184V and one with K70R. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K70R;M184V 130;111 134;116 NRTI 75 79 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. One participant who received EFV+d4T+3TC had four RT mutations (A62V, K65R, M184V, and K219E) in addition to two NNRTI-associated mutations. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV A62V;K219E;K65R;M184V 64;87;70;76 68;92;74;81 NNRTI;RT 113;50 118;52 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. The most common was M184V, found in 14 of 40 (35.0%) 3TC-recipients. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 20 25 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. The N348I mutation of the connection domain of RT was detected in two participants; both also had NNRTI mutations. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV N348I 4 9 NNRTI;RT 98;47 103;49 21698125 Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe. Some sequences contained recently described mutations that may reduce the susceptibility to etravirine; E28K (0.84%), V90I (0.42%) and E138Q (0.42%). 2011 PloS one Result HIV E138Q;E28K;V90I 135;104;118 140;108;122 21698125 Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe. The mutations present were PR I85V in Subtype C Drug Resistance (SCR) patient identity number 423 (SCR423), and RT Y181C in SCR541 selected by PIs and NNRTIs respectively. 2011 PloS one Result HIV I85V;Y181C 30;115 34;120 NNRTI;PI;PR;RT 151;143;27;112 157;146;29;114 21698125 Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe. The specimen with the Y181C mutation also had the nucleoside reverse transcriptase inhibitor (NRTI) selected mutation, T69A. 2011 PloS one Result HIV T69A;Y181C 119;22 123;27 NRTI;NRTI 50;94 82;98 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Adding stabilized weights to the model exposed a greater deleterious effect of M184X on pVL ( units) when uncompensated by K103X and/or K219X. 2011 PloS one Result HIV K103X;K219X;M184X 124;137;79 129;142;84 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. An interaction term between D67 and K219, which was encountered in the preceding model on CD4, was also statistically significant in this model of pVL with the presence of K219X diminishing the effect of D67X on pVL by about 0.6 units. 2011 PloS one Result HIV D67X;K219X 205;173 209;178 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Based on the results of the preceding section, we focussed on the compensated and uncompensated effects of M184X on baseline pVL, and of D67X on both pVL and . 2011 PloS one Result HIV D67X;M184X 137;107 141;112 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Consequently, the multinomial outcome comprised 1445, 19 and 15 cases for the respective levels 0, 1 and 2 (i.e., wildtype, uncompensated M184X, and M184X compensated by K103X and/or K219X). 2011 PloS one Result HIV K103X;K219X;M184X;M184X 171;184;139;150 176;189;144;155 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. D67X and K219X were each associated with significantly lower baseline CD4 (; Table 3); both sets of SDRMs are thymidine analog mutations (TAMs) conferring resistance to NRTIs. 2011 PloS one Result HIV K219X;D67X 9;0 14;4 NRTI 169 174 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. For both pVL and CD4, the effects of D67X compensated by K219X became statistically significant and reversed sign relative to the unadjusted models (Table 4). 2011 PloS one Result HIV D67X;K219X 37;57 41;62 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. For instance, interactions between M184X and either K103X or K219X were associated with a compensatory increase in pVL ( and , respectively; Figure 5). 2011 PloS one Result HIV K103X;K219X;M184X 52;61;35 57;66;40 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. In addition, there was a significant interaction effect between D67X and K219X associated with a compensatory increase by about 2.5 units (; Figure 5). 2011 PloS one Result HIV D67X;K219X 64;73 68;78 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. In an unweighted univariate linear model, M184X was significantly associated with a decline in pVL in the absence of K103X and/or K219X (Table 4). 2011 PloS one Result HIV K103X;K219X;M184X 119;132;42 124;137;47 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. K103X and K219X were assumed to be interchangeable with respect to their compensatory interactions with M184X. 2011 PloS one Result HIV K219X;M184X;K103X 10;104;0 15;109;5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. M184X was significantly associated with an approximately ten-fold lower pVL at baseline (; Table 3). 2011 PloS one Result HIV M184X 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. M46X and L210X were also significantly associated with lower baseline pVL and D67X was associated with greater pVL . 2011 PloS one Result HIV D67X;L210X;M46X 79;9;0 83;14;4 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Similarly, a decline in pVL associated with M46X was compensated by T215X . 2011 PloS one Result HIV M46X;T215X 44;68 48;73 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Similarly, re-weighting linear models resulted in larger estimated effects of uncompensated D67X on both baseline CD4 (2.1 units ) and pVL (2.5-fold increase; Table 4). 2011 PloS one Result HIV D67X 92 96 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Stabilized weights adjusting for the conditional probability of carrying D67X ranged from 0.006 to 12.3 with a mean of 1.003. 2011 PloS one Result HIV D67X 73 77 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Stabilized weights adjusting for the conditional probability of carrying M184X ranged from 0.02 to 18.72 with a mean of 1.016. 2011 PloS one Result HIV M184X 73 78 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. The presence or absence of SDRMs at each position was represented by a binary variable (herein denoted by appending an 'X' to the amino acid positional notation, e.g., M46X = {0,1}). 2011 PloS one Result HIV M46X 168 172 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Allele-specific real-time PCR and direct sequencing detected K103N mutants at the same time in the 3 other patients (patients 17, 18, and 19). 2011 PloS one Result HIV K103N 61 66 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Allele-specific real-time PCR detected minor K103N mutants in 9 more patients than did direct sequencing; the frequency of K103N mutants was <0.1% in 7 of them, and 1% and 2.8% in the 2 others. 2011 PloS one Result HIV K103N;K103N 45;123 50;128 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. An average of 3592 analyzable reads was obtained per sample, which enable minor K103N variants accounting for 1.4% of the quasispecies to be detected. 2011 PloS one Result HIV K103N 80 85 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. By contrast, the emergence of K103N mutations in the other 8 patients with >0.1% K103N mutants resulted in treatment failure in 3 of them; the remaining 5 maintained a virological response to cART during on-therapy periods (plasma virus load <=400 copies/mL). 2011 PloS one Result HIV K103N;K103N 30;81 35;86 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. By contrast, treatment failure did not occur in 5 patients despite the presence of K103N mutants: the frequency of K103N mutants remained quite low (maximum 1% and 2.8%) in patients 12 and 14, it was high (48.4%) in another (patient 16) who was also given indinavir in addition to efavirenz and lamivudine, and the frequencies of K103N mutants were high (24.9%, and 84.7%) in the remaining 2 patients (patients 13 and 18) who were given only two nucleoside reverse transcriptase inhibitors plus efavirenz. 2011 PloS one Result HIV K103N;K103N;K103N 83;115;330 88;120;335 NRTI 446 478 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Detection of K103N mutations by allele-specific real-time PCR. 2011 PloS one Result HIV K103N 13 18 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Detection of K103N mutations by ultra-deep pyrosequencing. 2011 PloS one Result HIV K103N 13 18 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Impact of variations in the pharmacokinetics of efavirenz on K103N mutation emergence. 2011 PloS one Result HIV K103N 61 66 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Influence of emergent K103N mutations on the subsequent virological response to cART. 2011 PloS one Result HIV K103N 22 27 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. It had no influence on the virological response to cART in the 7 patients whose frequency of K103N mutants remained <0.1% without further selection. 2011 PloS one Result HIV K103N 93 98 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. K103N mutants were abundant in 2 patients (patients 17 and 19) who were on stavudine, didanosine, and efavirenz, one from the end of the first off-therapy period (99.6%) and the other from the end of the second (85.5%); they experienced treatment failure thereafter. 2011 PloS one Result HIV K103N 0 5 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. K103N mutants were detected at the end of an off-therapy period in 15 of the 19 analyzable patients by allele-specific real-time PCR, but in only 6 of these 19 patients by direct sequencing. 2011 PloS one Result HIV K103N 0 5 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Lastly, the initial frequency of K103N mutants was above 10% in 2 of the 15 patients (Table 1). 2011 PloS one Result HIV K103N 33 38 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The absolute numbers of drug-resistant copies in patients with low frequencies of K103N mutants who experienced subsequent selection of their mutated virus populations were 1.54 log10 (0.24%, patient 13), 3.65 log10 (1.9%, patient 15), 3.97 log10 (5.8%, patient 16), and 3.04 log10 (5% ; patient 17) per mL plasma when first detected by allele-specific real-time PCR (Table 2). 2011 PloS one Result HIV K103N 82 87 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The allele-specific real-time PCR to detect K103N mutations could not be performed in 2 patients (harboring wild-type viruses by direct sequencing) because of amplification failure. 2011 PloS one Result HIV K103N 44 49 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The frequencies and copy numbers of K103N mutants quantified in parallel by allele-specific real-time PCR and ultra-deep pyrosequencing were strongly correlated (rho = 0.79 P<0.001, and rho = 0.89 P<0.0001, respectively). 2011 PloS one Result HIV K103N 36 41 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The frequencies of K103N mutants in these latter 3 patients were 5% (at week 8), 99.6% (at week 8), and 24.9% (at week 72) when they were detected by both methods. 2011 PloS one Result HIV K103N 19 24 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The frequencies of K103N mutants were 0.24%, 1.9%, and 5.8% in these 3 patients when they were first detected by allele-specific real-time PCR at week 40, and they increased to 84.7%, 29.9%, and 11% when detected later by direct sequencing. 2011 PloS one Result HIV K103N 19 24 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The frequency of K103N mutants in the quasispecies remained below 0.1% throughout follow-up in 7 of these 15 patients, without further selection. 2011 PloS one Result HIV K103N 17 22 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The gradual emergence of K103N mutants was first detected by allele-specific real-time PCR during the third off-therapy period (1.9% at week 40), and the mutated population was then selected at each cycle until the virus population was almost totally mutated (91.9%) at week 88. 2011 PloS one Result HIV K103N 25 30 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The initial frequency of K103N mutants was 0.1-1% in 2 of the 15 patients, and further increased to become predominant in one of them. 2011 PloS one Result HIV K103N 25 30 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The initial frequency of K103N mutants was 1-10% in 4 of the 15 patients, with further selection in 3 of them. 2011 PloS one Result HIV K103N 25 30 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The K103N mutants detected by allele-specific real-time PCR in 6 patients were also detected by direct sequencing (Table 1). 2011 PloS one Result HIV K103N 4 9 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The median efavirenz half-life was 32 hours (CI95 [28.7-75.3]) in patients harboring no or few (<0.1%) K103N mutants (n = 11), and 50.5 hours (CI95 [45.1-99.6]) in patients in whom allele-specific real-time PCR detected a significant frequency (>0.1%) of K103N mutants (n = 8) (P = 0.04). 2011 PloS one Result HIV K103N;K103N 103;255 108;260 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The number of K103N copies per mL of plasma was calculated by multiplying the proportion of K103N mutants by the plasma virus load. 2011 PloS one Result HIV K103N;K103N 14;92 19;97 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The presence of the K103N mutation was assessed by ultra-deep pyrosequencing in 11 of the patients for whom enough plasma samples were available. 2011 PloS one Result HIV K103N 20 25 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Ultra-deep pyrosequencing did not detect the K103N mutants that were detected by allele-specific real-time PCR at the same stage in 5 samples (frequencies of 0.03%, 0.05%, 0.1%, 1%, and 1.7%), but higher frequencies were detected by both methods with good agreement (Table 2). 2011 PloS one Result HIV K103N 45 50 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We analyzed the impact of emergent K103N mutants on the subsequent virological response to cART in the 15 patients in whom K103N mutants had been detected by allele-specific real-time PCR. 2011 PloS one Result HIV K103N;K103N 35;123 40;128 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. After carefully analyzing the mutations of these resistant viral strains, we discovered that one single mutation M184V may lead to the substantially reduced antiviral activity of 11. 2011 European journal of medicinal chemistry Result HIV M184V 113 118 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. In our screening, 11 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR, with EC50 values of 0.086, 0.15, and 0.11 nM, respectively. 2011 European journal of medicinal chemistry Result HIV K101E 100 105 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. In the further evaluation of 11, we discovered that it retained its sub-nanomolar activity against drug-resistant HIV strains NL4-3 (K101E) and RTMDR (Table 2). 2011 European journal of medicinal chemistry Result HIV K101E 133 138 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. K101E tends to decrease viral susceptibility to all nucleoside RT inhibitors, while RTMDR is a multiple RT inhibitor-resistant strain, which is insensitive to AZT, ddI, nevirapine, and other NNRTIs. 2011 European journal of medicinal chemistry Result HIV K101E 0 5 NNRTI;RT;RT 191;63;104 197;65;106 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. NRTI resistant viruses with D67N or M184V mutation are markedly resistant to compound 10. 2011 European journal of medicinal chemistry Result HIV D67N;M184V 28;36 32;41 NRTI 0 4 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. This M184V mutation in RT was discovered previously to be 3TC treatment-associated, and it was also found that the M184V mutation increases the HIV sensitivity to AZT in AZT-resistant viruses, suggesting that compound 11 may be used in combination with AZT to reduce the influence of resistance issues. 2011 European journal of medicinal chemistry Result HIV M184V;M184V 5;115 10;120 RT 23 25 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. At baseline, the M184V mutation was detected in three and the K103N mutation in four patients at low frequencies; patient 115 harbored both variants (figure 1; table 1). 2011 PloS one Result HIV K103N;M184V 62;17 67;22 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Baseline characteristics were similar between patients with and without minority K103N and/or M184V HIV-1 variants prior to early ART in terms of viral load at baseline (median [range] HIV-1 RNA copies/ml plasma: 5.0x104 [3.6x103-3.6x106] vs. 2011 PloS one Result HIV K103N;M184V 81;94 86;99 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. During this time, the K103N mutation was once not detectable (individually calculated detection limit based on the viral load for this time point: 0.03%). 2011 PloS one Result HIV K103N 22 27 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. In addition, the first two time points after treatment interruption were also negative for the K103N mutation, however, the individually calculated detection limits were higher for these samples compared with the following time points due to lower viral loads (0.36% and 0.09%, respectively). 2011 PloS one Result HIV K103N 95 100 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. In patient 123, the K103N mutation reappeared 2.2 months after treatment interruption and fluctuated between 0.06 and 0.52% within the following 15 months in the absence of ART. 2011 PloS one Result HIV K103N 20 25 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. In patient 141, the M184V mutation was not present prior to early ART, but appeared in 2/5 samples after treatment interruption. 2011 PloS one Result HIV M184V 20 25 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. In patient 174, the K103N mutation reappeared in one of five time points. 2011 PloS one Result HIV K103N 20 25 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. In total, 43 and 45 longitudinal samples after treatment interruption were measured by AS-PCR for the mutations K103N and M184V in patients with and without these variants at low frequencies prior to early ART, respectively. 2011 PloS one Result HIV K103N;M184V 112;122 117;127 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Minority K103N and/or M184V HIV-1 variants were previously detected at the earliest available time point during acute or recent HIV-1 infection and before initiation of ART in 15 of 109 patients included in the ZPHI between March 2002 and December 2007. 2011 PloS one Result HIV K103N;M184V 9;22 14;27 HIV infections 128 143 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Reinitiation of ART was efficient to suppress viremia below detectable limits within a few weeks in all patients who reinitiated ART independent of the detection of minority K103N and/or M184V HIV-1 variants during treatment interruption (figure 1). 2011 PloS one Result HIV K103N;M184V 174;187 179;192 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. The K103N mutation was detected during treatment interruption in two patients harboring this mutation at low frequencies prior to early ART (figure 1). 2011 PloS one Result HIV K103N 4 9 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. The K103N mutation was neither detected during treatment interruption in the other two patients harboring this variant nor in the 13 patients not harboring minority K103N HIV-1 variants during primary HIV-1 infection. 2011 PloS one Result HIV K103N;K103N 4;165 9;170 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. The M184V mutation was detected three times in two patients (figure 1): In patient 162, this variant was present at baseline and reappeared once in the last of eight samples during treatment interruption. 2011 PloS one Result HIV M184V 4 9 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Thus, six patients with and 11 patients without minority K103N and/or M184V HIV-1 variants prior to early ART were studied. 2011 PloS one Result HIV K103N;M184V 57;70 62;75 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. 3 and Table S1), suggestive that the relative contribution of the S138A substitution to infectivity rescue might also involve other determinants. 2011 PloS one Result HIV S138A 66 71 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. All intermediate and late Env clones (weeks 59 and 94) carried the N43D mutation with the N126K substitution, although in contrast to patient C, phenotypic resistance levels did not increase further under prolonged treatment. 2011 PloS one Result HIV N126K;N43D 90;67 95;71 Env 26 29 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. All the pre-treatment viral env clones from patient B carried the N42S polymorphism (Table S1). 2011 PloS one Result HIV N42S 66 70 Env 28 31 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Among the polymorphisms previously described to modulate viral infectivity, compensatory mutation S138A was detected in 5/9 escape Envs from patient B, in 9/10 intermediate and late escape Envs from patient D (but in none of the early escape Envs) and in all viral escape clones from patient E (Table S1). 2011 PloS one Result HIV S138A 98 103 Env;Env;Env 131;189;242 135;193;246 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. At later time points, only the V38A mutation was detected associated with the L44M resistance mutation. 2011 PloS one Result HIV L44M;V38A 78;31 82;35 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Early resistance mutations (G36D and N42S+N43D) conferred high level resistance (>100-fold) and persisted throughout treatment. 2011 PloS one Result HIV G36D;N42S;N43D 28;37;42 33;41;46 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. For patient C, 4/5 early escape viruses carried the G36D substitution and one clone carried the V38A mutation. 2011 PloS one Result HIV G36D;V38A 52;96 56;100 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. For patient C, all late (week 129) clones were extremely tightly related and emerged from the branch grouping early G36D variants (clones 27.3, 27.4, 27.6) rather than from the early V38A variant or from the intermediate V38A+L45M variants. 2011 PloS one Result HIV G36D;L45M;V38A;V38A 116;226;183;221 120;230;187;225 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. For patient D, 3/5 early env clones carried the N43D resistance mutation and one infectious clone carried the N42D+N43S mutations. 2011 PloS one Result HIV N42D;N43D;N43S 110;48;115 114;52;119 Env 25 28 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. For patient E, the impact of E137K is difficult to evaluate as only intermediate clones were recovered and as gains in viral infectivity seem to map to env determinants outside of HR1-HR2. 2011 PloS one Result HIV E137K 29 34 Env 152 155 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. In all patients, however, the RIs of variants carrying the S138A mutation were comparable to those of variants carrying wild-type S138. 2011 PloS one Result HIV S138A 59 64 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. In contrast, the N126K compensatory mutation in patient D viruses was detected exclusively in on-treatment viral sequences, pointing to it as a presumed contributor to the parallel infectivity gains of HR1-HR2 and full Env recombinants. 2011 PloS one Result HIV N126K 17 22 Env 219 222 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Other mutations included substitutions N125D (patients A, B and C), N125S and N126K (patient D) and E137K (patient E) (Table S1). 2011 PloS one Result HIV E137K;N125D;N125S;N126K 100;39;68;78 105;44;73;83 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Taken together, our data suggest that both compensatory mutations within HR1-HR2 (N126K for patient D, yet unidentified determinants for patient C) and the env genetic context (patients A, B and E) contribute to increased viral infectivity. 2011 PloS one Result HIV N126K 82 88 Env 156 159 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. The N125D/S polymorphisms within HR2 were detected in both baseline and escape clones, arguing against them playing a pivotal role in restoring infectivity. 2011 PloS one Result HIV N125D;N125S 4;4 11;11 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. The N43D mutants were 2 to 6-fold more resistant than the N42D+N43S double mutant for both HR1-HR2 and full Env recombinants. 2011 PloS one Result HIV N42D;N43D;N43S 58;4;63 62;8;67 Env 108 111 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. The V38A (patient C) and N43D (patient D) mutations conferred higher resistance than the G36D (patient C) or N42D+N43S (patient D) mutations respectively, and at intermediate and late time points, the early G36D and N42D+N43S variants were outcompeted by V38A or the N43D variants. 2011 PloS one Result HIV G36D;G36D;N42D;N42D;N43D;N43D;N43S;N43S;V38A;V38A 89;207;109;216;25;267;114;221;4;255 93;211;113;220;29;271;118;225;8;259 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. The V38A variant featured 4-fold (full Env) and 6-fold (HR1-HR2) higher resistance than the early G36D clones. 2011 PloS one Result HIV G36D;V38A 98;4 102;8 Env 39 42 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. These observations suggest that the higher level of resistance conferred by the V38A or the N43D mutations drove the selection of Envs between early and intermediate/late time points. 2011 PloS one Result HIV N43D;V38A 92;80 96;84 Env 130 134 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. In addition, OLA detected 4 resistance mutations in 4 women that were not detected by sequencing, including the mutations encoding K103N, Y181C, M184V, and K70R. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;K70R;M184V;Y181C 131;156;145;138 136;160;150;143 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. K103N was detected in 3/8 (38%), one also had Y181C, and G190A was detected in a fourth participant. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;Y181C;K103N 57;46;0 62;51;5 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. M184V was detected in the majority of women randomized to NFV 6/8 (75%, 95%CI 35-97) compared to only 1/8 (13%, 95%CI 0-53) given NVP, P=0.04. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 0 5 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. New resistance mutations were detected in specimens from 4 of these (3/5 NFV and 1/3 NVP), including Participant #10 with L90M and K70R present at entry and newly detected M184V (Table 2). 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K70R;L90M;M184V 131;122;172 135;126;177 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. Several mutations associated with drug resistance that were not evaluated by OLA were detected by consensus sequencing, including M41L, V118I, E138A, and L210W. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV E138A;L210W;M41L;V118I 143;154;130;136 148;159;134;141 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. She had ART-associated suppression of viral replication, but subsequently her virus rebounded with the L90M and K70R mutations and M184V was newly detected. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K70R;L90M;M184V 112;103;131 116;107;136 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The L90M mutation was estimated at 100% in both her pre-ART plasma and PBMC, highly suggestive of transmitted drug-resistance. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV L90M 4 8 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The new NRTI mutations included M184V associated with resistance to 3TC/FTC, and K70R and T215Y associated with resistance to thymidine analogs. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K70R;M184V;T215Y 81;32;90 85;37;95 NRTI 8 12 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The T215 codon was indeterminate in plasma virus by OLA, suggestive of a transitional mutation, which by consensus sequencing was T215D. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV T215D 130 135 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The woman assigned to NFV (Participant #10, Figure 2), had mutations conferring resistance to two classes of ARV at enrollment (L90M and K70R) and selected M184V during study ART. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV K70R;L90M;M184V 137;128;156 141;133;161 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The woman assigned to NVP (Participant #12, Figure 2), had T215Y by OLA at low concentrations in her enrollment PBMC. 2011 Journal of acquired immune deficiency syndromes (1999) Result HIV T215Y 59 64 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Conversely, 52 were enzymatically resistant to 3TC with 51 strains harboring M184V. 2011 PloS one Result HIV M184V 77 82 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Enzymatic NVP resistance was associated with the presence of K103N, Y181C/I, Y188L, G190A/Q, or K238N in 88 of the 91 samples. 2011 PloS one Result HIV G190A;G190Q;K103N;K238N;Y181C;Y181I;Y188L 84;84;61;96;68;68;77 91;91;66;101;75;75;82 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Figure 1B shows that the mean DeltaCt for NVP seen in 83 WT isolates was 7.42+-3.18 (range 0.235-15.9) compared to a mean DeltaCt value of 0.484+-0.963 (range -1.85-2.15) seen in 28 NVP-resistant samples carrying K103N, Y181C/I, Y188L, or G190A/Q (P<0.0001). 2011 PloS one Result HIV G190A;G190Q;K103N;Y181C;Y181I;Y188L 239;239;213;220;220;229 246;246;218;227;227;234 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. For instance, all 55 samples that had M184V were classified as 3TC-resistant while all 28 samples carrying NVP-associated mutations were considered NVP-resistant. 2011 PloS one Result HIV M184V 38 43 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. In three of the four strains with reduced enzymatic susceptibility to 3TC in the absence of 184I/V we found the mutation V118I which has been previously associated with low-level enzymatic resistance to 3TC-TP. 2011 PloS one Result HIV V118I 121 126 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. No NVP resistance mutation had been found in 95, one had a mixed genotype K103 K/N and 6 contained the mutations K103N, G190A, or Y188L. 2011 PloS one Result HIV G190A;K103K;K103N;K103N;Y188L 120;74;74;113;130 125;82;82;118;135 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Of 110 samples categorized sensitive for 3TC by Amp-RT only one had the mutation M184V, the corresponding DeltaC of 2.79 was only slightly above the cut-off (Figure 2A). 2011 PloS one Result HIV M184V 81 86 RT 52 54 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Of the 74 samples with phenotypic resistance to 3TC, 70 (94%) had the M184 V or M184I mutations. 2011 PloS one Result HIV M184I;M184V 80;70 85;76 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Of the 8 samples that had an M184 M/V mixture, 5 were Amp-RT resistant and 3 had DeltaCt values below 4.1. 2011 PloS one Result HIV M184M;M184V 29;29 37;37 RT 58 60 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Of the 99 samples 3TC-sensitive by Amp-RT, 94 (96%) were genotypically WT, 3 had a mixture of M184 M/V, and 2 showed M184 V. 2011 PloS one Result HIV M184M;M184V;M184V 94;94;117 102;102;123 RT 39 41 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Of the other remaining 9 samples, 2 had the K103N mutation and a DeltaCt value close to the assay cut-off (3.8 and 3.4), and 7 had mixtures of WT and mutant genotypes. 2011 PloS one Result HIV K103N 44 49 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. On the other hand the NVP-resistant strain Y188C X403-4 resulted in a mean of 8.4 (range 6.9-9.7) for 3TC and 1.9 (range 1.3-2.7) for NVP. 2011 PloS one Result HIV Y188C 43 48 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. The mean DeltaCt for 3TC in 56 WT isolates was 6.2+-2.5 (range 0.29-11.2) and was significantly higher (P<0.0001) than the mean DeltaCt seen in the 55 3TC-resistant isolates that had the M184V mutation (0.2+-0.8, range -1.6-2.1, Figure 1A). 2011 PloS one Result HIV M184V 187 192 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. The two samples with M184 V had DeltaCt values of 2.7 and 2.8, which were close to the assay cut-off (2.66). 2011 PloS one Result HIV M184V 21 27 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. 1) indicate that both Q91A and Q91N mutant enzymes are severely impaired in their polymerase activity in relation to the wild-type enzyme on both RNA and DNA templates. 2011 Biochemistry Result HIV Q91A;Q91N 22;31 26;35 Pol 82 92 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. 2) indicates that Q91N substitution confers higher resistance on the ddNTP analogs. 2011 Biochemistry Result HIV Q91N 18 22 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. A second substitution at position 184 (M184V) improved the affinity for these analogs with lower Ki and IC50 values as compared to the single mutants. 2011 Biochemistry Result HIV M184V 39 44 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. An E89G substitution reportedly confers multiple resistances to ddNTPs in cell-free analysis. 2011 Biochemistry Result HIV E89G;E89G 4;3 8;7 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. As compared to the wild-type as well as the Q91A/M184V and Q91N/M184V mutants, Q91N mutant seems to be more discriminatory for incorporation of dNTP, as well as the extension of primers, once a misinsertion has taken place. 2011 Biochemistry Result HIV M184V;M184V;Q91A;Q91N;Q91N 49;64;44;59;79 54;69;48;63;83 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. As depicted in Figure 5, Q91A, Q91N, and Q91A/M184V derivatives were much less efficient in the catalysis of pyrophosphorolysis activity on both DNA and RNA templates. 2011 Biochemistry Result HIV M184V;Q91A;Q91A;Q91N 46;25;41;31 51;29;45;35 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. As expected both Q91A and Q91N displayed higher Ki and IC50 values as compared to M184V and the wild type enzyme. 2011 Biochemistry Result HIV M184V;Q91A;Q91N 82;17;26 87;21;30 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. As expected, M184V mutant displayed kinetic behavior similar to the wild type enzyme. 2011 Biochemistry Result HIV M184V 13 18 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. As shown in Figure 4, none of the mutant RT derivatives have incorporated rNTPs as much as seen by wild-type RT, although extent of rNTP incorporation by Q91N/M184V mutant derivative was similar to the wild type enzyme. 2011 Biochemistry Result HIV M184V;Q91N 159;154 164;158 RT;RT 41;109 43;111 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. have reported a concomitant increase in the processivity of the mutant enzyme D76N, K70R, T215F, and K219Q to compensate for the increased pyrophosphorolysis, which they attribute to alterations T215F and K219Q. 2011 Biochemistry Result HIV D76N;K219Q;K219Q;K70R;T215F;T215F;D76N;K219Q;K219Q;K70R;T215F;T215F 79;102;206;85;91;196;78;101;205;84;90;195 83;107;211;89;96;201;82;106;210;88;95;200 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. have reported such enhanced pyrophosphorolysis in HIV-1 RT due to mutations D76N/K70R in the high-level resistance mutants D76N, K70R, T215F, and K219Q. 2011 Biochemistry Result HIV D76N;D76N;K219Q;K70R;K70R;T215F 76;123;146;81;129;135 80;127;151;85;133;140 RT 56 58 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. If use of rNTP as compared to that of dNTP can be taken as a function of enzyme fidelity, then this result supports our earlier observation that Q91N exhibits increased fidelity. 2011 Biochemistry Result HIV Q91N 145 149 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. In contrast, the Q91N and Q91N/M184V double mutant showed no significant change in their Km value for dGTP substrate with 2-3 fold decrease in their catalytic efficiency on poly rA template and 5-10 fold decrease on poly rC template. 2011 Biochemistry Result HIV M184V;Q91N;Q91N 31;17;26 36;21;30 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. In the case of Q91N, comparison of the lane representing synthesis in the absence of ddNTP. 2011 Biochemistry Result HIV Q91N 15 19 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Interestingly, the extent of primer extension exhibited by Q91N mutant was greatly reduced as compared to the wild-type enzyme. 2011 Biochemistry Result HIV Q91N 59 63 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. It is possible that the observed resistance to ddNTP of Q91A and Q91N mutant enzymes could be due to increased pyrophosphorolysis activity, which can generate 3'-OH by cleaving the ddNTP-terminated primer. 2011 Biochemistry Result HIV Q91A;Q91N;Q91A;Q91N 57;66;56;65 61;70;60;69 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Most interestingly, the deleterious effect of the mutation was reduced when the M184V mutation was introduced in addition to Q91A, while the Q91N/M184V mutant showed activity similar to that of the wild-type enzyme. 2011 Biochemistry Result HIV M184V;M184V;Q91A;Q91N 80;146;125;141 85;151;129;145 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Mutant enzymes such as M184V, E89G, and M184L have been shown to exhibit higher enzyme fidelity than does the wild-type enzyme. 2011 Biochemistry Result HIV E89G;M184L;M184V 30;40;23 34;45;28 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Notably, the observed "pausing" pattern of Q91N mutant enzyme is similar on both RNA and DNA templates. 2011 Biochemistry Result HIV Q91N 43 47 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Of the four mutant derivatives studied in this work, Q91N/M184V, independent of the template used, was comparable to wild-type enzyme in its pyrophosphorolysis activity. 2011 Biochemistry Result HIV M184V;Q91N 58;53 63;57 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Of the two mutant enzymes, Q91N mutant enzyme seems to be more discriminatory than is the WT enzyme. 2011 Biochemistry Result HIV Q91N 27 31 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Polymerase activity of the Q91A seems to be severely impaired, leaving the enzyme almost defective; Q91N mutant enzyme also shows much less activity. 2011 Biochemistry Result HIV Q91A;Q91N 27;100 31;104 Pol 0 10 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Q91N mutant seems to pause more frequently and accumulate shorter products, although the degree of initial primer use is similar to that by the wild-type enzyme. 2011 Biochemistry Result HIV Q91N 0 4 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Resistant variants containing an M184I alteration in RT gene appear transiently and then are replaced by those with M184V alteration. 2011 Biochemistry Result HIV M184I;M184V 33;116 38;121 RT 53 55 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Similar 5-10 fold increase in KmdGTP for Q91A and Q91A/M184V mutants was noted on homopolymeric poly-rC.dG18 template with corresponding 27-32 fold decrease in the catalytic efficiency. 2011 Biochemistry Result HIV M184V;Q91A;Q91A 55;41;50 60;45;54 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The double mutants at positions 91 and 184 were Q91N/M184V and Q91A/M184V. 2011 Biochemistry Result HIV M184V;M184V;Q91A;Q91N 53;68;63;48 58;73;67;52 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The kinetic parameters of the mutant derivatives of Q91 determined using homopolymeric poly-rA.dT18 and poly-rC.dG18 templates indicated a drastic reduction in the utilization of substrate (higher KmdTTP) by both Q91A and its double mutant derivative Q91A/M184V while Q91N and its double mutant derivative, Q91N/M184V displayed KmdTTP similar to the wild type enzyme A 10-12 fold increase in Km for dTTP for the Q91A and Q91A/M184V mutants on the homopolymeric poly-rA.dT18 template was noted with corresponding 21- and 43-fold decrease in the catalytic efficiency, respectively (Table 2). 2011 Biochemistry Result HIV M184V;M184V;M184V;Q91A;Q91A;Q91A;Q91A;Q91N;Q91N 256;312;426;213;251;412;421;268;307 261;317;431;217;255;416;425;272;311 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The M184V mutant higher Ki values for ddTTP and ddGTP as compared to the wild type enzyme but lower than the single and double mutants. 2011 Biochemistry Result HIV M184V 4 9 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The polymerase activity of double mutants Q91A/M184V and Q91N/184V was significantly improved on both the template primers. 2011 Biochemistry Result HIV M184V;Q91A;Q91N 47;42;57 52;46;61 Pol 4 14 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The Q91N mutant derivative of RT seems to be more discriminatory than are the Q91A/M184V and Q91N/M184V double mutant derivatives for both the DNA and RNA templates. 2011 Biochemistry Result HIV M184V;M184V;Q91A;Q91N;Q91N 83;98;78;4;93 88;103;82;8;97 RT 30 32 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The results shown in Table 1 indicate that polymerase activity of Q91A mutant is only 8-12% of the WT activity on both the heteromeric and homopolymeric TP whereas Q91N retained 30% activity with the heteromeric U5-PBS TP while 56% activity was observed with the homopolymeric poly rA/dT TP. 2011 Biochemistry Result HIV Q91A;Q91N 66;164 70;168 Pol 43 53 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. These results suggest that the substitution has affected the enzyme activity in a manner similar to that affected by E89G or Y183F alteration. 2011 Biochemistry Result HIV E89G;Y183F 117;125 121;130 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. This M184V mutation has also been shown to confer low-level resistance on ddI and ddC. 2011 Biochemistry Result HIV M184V;M184V 6;5 11;10 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Thus it is possible that the decreased polymerase activity of both Q91A and Q91N may be due to subtle changes in the dNTP binding pocket. 2011 Biochemistry Result HIV Q91A;Q91N 67;76 71;80 Pol 39 49 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Thus it was interesting to examine whether Q91A and Q91N mutations, either separately or in the presence of double mutation M184V, influence these functions of the enzyme. 2011 Biochemistry Result HIV M184V;Q91A;Q91N 124;43;52 129;47;56 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. While Q91A/M184V double mutant also shows resistance to ddNTPs, Q91N/M184V double mutant shows sensitivity similar to the wild-type enzyme. 2011 Biochemistry Result HIV M184V;M184V;Q91A;Q91N 11;69;6;64 16;74;10;68 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. A different lineage derived from the same ancestral group emerged at month 5 and acquired the Q148H + G140S mutations, which persisted there-after. 2011 AIDS (London, England) Result HIV G140S;Q148H 102;94 107;99 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. A few substitutions show potential significance, including Y143H in all participants and Q148R in participant 3. 2011 AIDS (London, England) Result HIV Q148R;Y143H 89;59 94;64 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. After 3 months of therapy, N155H, Q148K, and Q148R all coexisted (Figs 2a and 3b). 2011 AIDS (London, England) Result HIV N155H;Q148K;Q148R 27;34;45 32;39;50 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. At month 12, Q148H was the majority but N155H was still detectable, whereas Y143R was not. 2011 AIDS (London, England) Result HIV N155H;Q148H;Y143R 40;13;76 45;18;81 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. By month 4, only the N155H variants were detected, whereas by month 8 Y143R, Q148H, and N155H all were detected. 2011 AIDS (London, England) Result HIV N155H;N155H;Q148H 21;88;77 26;93;82 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Each of the collections of DRMs (N155H, Q148R, and Q148H + G140S) was found on both backgrounds. 2011 AIDS (London, England) Result HIV G140S;N155H;Q148H;Q148R 59;33;51;40 64;38;56;45 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Even though the most common substitution at position 148 at month 3 encodes Q148R, it does not occur together with any accessory mutations at codon 138 or 140. 2011 AIDS (London, England) Result HIV Q148R 76 81 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Following correction for multiple comparisons, Y143H attained significance in both patient 1 and 3, but no other positions survived the test for multiple comparisons. 2011 AIDS (London, England) Result HIV Y143H 47 52 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. However, after correction for multiple comparisons, only Y143H in participant 3 maintained significance. 2011 AIDS (London, England) Result HIV Y143H 57 62 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. However, for the G140S mutation, the codon is directly adjacent to the polymorphic codon 139, so in this case, recombination would need to break exactly between the two codons to generate the observed genotypes. 2011 AIDS (London, England) Result HIV G140S 17 22 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. In all three patients, N155H, which was the first DRM to arise after Raltegravir therapy, as well as Q148H, which was the majority primary DRM after pathway switch, were not significantly enriched in the pretreatment samples. 2011 AIDS (London, England) Result HIV N155H;Q148H 23;101 28;106 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. In patient 1 at month 3 after initiating treatment, N155H predominated, though there were rare variants with Q148R and Q148H present (Figs 2a and 3a). 2011 AIDS (London, England) Result HIV N155H;Q148H;Q148R 52;119;109 57;124;114 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. In patient 3, three clusters were detected at time 0, one of which went on to give rise to the N155H drug-resistant lineages by month 3. 2011 AIDS (London, England) Result HIV N155H 95 100 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. In the pyrosequence data, the majority of early primary mutations encoded N155H in all three patients, whereas the majority of later primary mutations encoded Q148H, confirming the pathway switch inferred from population genotyping. 2011 AIDS (London, England) Result HIV N155H;Q148H 74;159 79;164 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Patient 2 also showed N155H switching to Q148H + G140S, but N155H was still detected at low abundance even after 8 months of therapy and a complex collection of intermediateswere detected over the period sampled. 2011 AIDS (London, England) Result HIV G140S;N155H;N155H;Q148H 49;22;60;41 54;27;65;46 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Patient 2 was the only participant in whom Y143R and N155H were detectable at later time-points. 2011 AIDS (London, England) Result HIV N155H;Y143R 53;43 58;48 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Population genotyping with Sanger sequencing identified N155H as one of the first integrase DRMs to appear, but later the Q148H mutant predominated. 2011 AIDS (London, England) Result HIV N155H;Q148H 56;122 61;127 IN 82 91 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Q148H replaced N155H after 5 months. 2011 AIDS (London, England) Result HIV N155H;Q148H 15;0 20;5 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Some but not all of the Q148H codons were associated with G140S (middle of month 3 panel in Figs 2a and 3a). 2011 AIDS (London, England) Result HIV G140S;Q148H 58;24 63;29 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. The Q148K + E138K combination was evident at month 3, and though this combination is reported to be a potent RAL escape variant, it was not detected subsequently. 2011 AIDS (London, England) Result HIV E138K;Q148K 12;4 17;9 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Thus, independent mutation to generate the G140S substitution on the two backgrounds seems more likely. 2011 AIDS (London, England) Result HIV G140S 43 48 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. We also detected T97A, an accessory mutation for Y143R, and L74M and E92Q, accessory mutations for N155H, from the forward read sets (data not shown). 2011 AIDS (London, England) Result HIV E92Q;L74M;N155H;T97A;Y143R 69;60;99;17;49 73;64;104;21;54 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. As noted above, 1 and 2 show no activity against the Y181C strain, though the CC50 for 1 is low (100-200 nM), which would mask any activity above that level. 2011 Journal of the American Chemical Society Result HIV Y181C 53 58 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. At this point, improvement in the CC50 values and the activity towards the Y181C variant need to be addressed. 2011 Journal of the American Chemical Society Result HIV Y181C 75 80 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. In addition, the fold-change (ratio of Y181C to WT activities) of only a factor of 2 for 36 and its greater potency towards the Y181C variant than for the reference NNRTIs, efavirenz and etravirine, are notable. 2011 Journal of the American Chemical Society Result HIV Y181C;Y181C 39;128 44;133 NNRTI 165 171 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. It also fills the space much better in this region for the Y181C variant (Figure 6, right) than for 1 or 2. 2011 Journal of the American Chemical Society Result HIV Y181C 59 64 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The cyclopropylpyrimidine 35 was found to perform similarly to its pyridine analog 19, while 6-fold gains in potency were obtained with 36 over 20 for both the WT virus and Y181C variant. 2011 Journal of the American Chemical Society Result HIV Y181C 173 178 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The first Y181C results for the thiomethylpyrimidine 17 and the cyclopropyl analog 19 were very encouraging with EC50 values of 250 and 160 nM. 2011 Journal of the American Chemical Society Result HIV Y181C 10 15 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The remaining issue is the performance of the designs incorporating the 3-cyanovinylphenoxy group on the troublesome Tyr181Cys-containing variant form of HIV-1. 2011 Journal of the American Chemical Society Result HIV Y181A;Y181C;Y181Delta;Y181G;Y181I;Y181N;Y181O;Y181T 117;117;117;117;117;117;117;117 126;126;126;126;126;126;126;126 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The resultant EC50 values for 36 of 2.5 nM (WT) and 4.9 nM (Y181C) are striking given the starting point of the original phenoxy compound 3. 2011 Journal of the American Chemical Society Result HIV Y181C 60 65 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The triazine 31 corresponding to 1 does show weak antiviral activity towards the Y181C variant (12.5 muM). 2011 Journal of the American Chemical Society Result HIV Y181C 81 86 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. Then, addition of the 5-Cl group in 20 achieved a significant milestone with EC50 values below 50 nM towards both the WT virus and the Y181C variant. 2011 Journal of the American Chemical Society Result HIV Y181C 135 140 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. All group A viruses harbored a Q148R resistance mutation, associated with G140S in two cases (patients T3 and T4) and G140A in two others (patients T5 and T7; Table 2). 2011 Retrovirology Result HIV G140A;G140S;Q148R 118;74;31 123;79;36 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Biochemical studies have demonstrated that Q148R, N155H and Y143C are primary resistance mutations giving rise to HIV-1 resistance whereas G140S/A and E92Q are secondary resistance mutations increasing resistance and viral fitness. 2011 Retrovirology Result HIV E92Q;G140A;G140S;N155H;Q148R;Y143C 151;139;139;50;43;60 155;146;146;55;48;65 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Both enzymes were active in vitro, suggesting that the impairment of the catalytic activity of the T2 IN (E92Q/Y143C) was not directly related to the presence of these mutations (Figure 6A). 2011 Retrovirology Result HIV E92Q;Y143C 106;111 110;116 IN 102 104 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. By contrast, introduction of the G140S mutation into the Q148R background yielded a protein that was highly resistant to RAL. 2011 Retrovirology Result HIV G140S;Q148R 33;57 38;62 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. By contrast, introduction of the Y143C mutation did not lead to significant resistance of the protein in vitro, suggesting that Y143C is not a primary RAL resistance mutation in HIV-2 IN. 2011 Retrovirology Result HIV Y143C;Y143C 33;128 38;133 IN 184 186 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. By contrast, the N155H mutation had no significant effect on IN activity. 2011 Retrovirology Result HIV N155H 17 22 IN 61 63 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. By contrast, the resistance level increased when E92Q was introduced into a Y143C resistant background (IC50 = 370 nM), suggesting that the concomitant presence of the two mutations was necessary for this significant increase in resistance. 2011 Retrovirology Result HIV E92Q;Y143C 49;76 53;81 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Comparison with the HIV-2 group A reference sequence ROD showed that all five group A sequences displayed the following polymorphisms V19I, R34K, S39T, A41T, T60V, I133V, I180V, I201T, E207D at positions that were previously showed to be subject to variation. 2011 Retrovirology Result HIV A41T;E207D;I133V;I180V;I201T;R34K;S39T;T60V;V19I 152;185;164;171;178;140;146;158;134 156;190;169;176;183;144;150;162;138 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Consistent with this hypothesis, the catalytic activity of the Y143C/N155H recombinant mutant was strongly increased by the addition of 10% DMSO (data not shown), probably because DMSO may help to stabilize partially folded conformations of proteins. 2011 Retrovirology Result HIV N155H;Y143C 69;63 74;68 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Finally, it has been suggested that the T97A mutation is involved in resistance to RAL. 2011 Retrovirology Result HIV T97A 40 44 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. HIV-2 IN harboring the mutation Q148R had a much lower level of catalytic activity (<10% wild-type levels) than the wild-type enzyme (Figure 3). 2011 Retrovirology Result HIV Q148R 32 37 IN 6 8 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. However, introduction of the Y143C mutation into an N155H background significantly decreased resistance levels, by one order of magnitude (IC50 = 290 nM) with respect to the resistant N155H-containing IN (Figure 5B). 2011 Retrovirology Result HIV N155H;N155H;Y143C 52;184;29 57;189;34 IN 201 203 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Introduction of the N155H mutation into the wild-type background also resulted in a high level of resistance (Figure 5B), with a fold-change with respect to the wild-type enzyme similar to that for the clinical isolate harboring the E92A/T97A/N155H triple mutation, which confirmed the identification of N155H as a primary resistance mutation for HIV-1 IN. 2011 Retrovirology Result HIV E92A;N155H;T97A;N155H;N155H 233;243;238;20;304 237;248;242;25;309 IN 353 355 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Introduction of the secondary mutation G140S into the Q148R background resulted in the partial recovery (up to 30% of wild-type levels) of IN catalytic activity, which was strongly impaired by the Q148R mutation. 2011 Retrovirology Result HIV G140S;Q148R;Q148R 39;54;197 44;59;202 IN 139 141 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Like Y143C, E92Q alone did not confer significant resistance to RAL in vitro. 2011 Retrovirology Result HIV E92Q;Y143C 12;5 16;10 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. N155H mutation, in conjunction with secondary substitutions at positions 92 and 97, increased the IC50 by a factor of about 50, whereas the IC50 was not reached for the G140S/Q148R double mutant, for concentrations up to 1 muM. 2011 Retrovirology Result HIV G140S;Q148R;N155H 169;175;0 174;180;5 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Nevertheless, IN harboring the T97A substitution has higher levels of activity, suggesting that T97A may increase the fitness of resistant viral mutants. 2011 Retrovirology Result HIV T97A;T97A 31;96 35;100 IN 14 16 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. One group B sequence harbored the N155H resistance mutation (patient T1), and another had the Y143C resistance mutation (patient T2) (Table 2). 2011 Retrovirology Result HIV N155H;Y143C 34;94 39;99 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Population sequencing results suggested that resistant viruses could harbor both the Y143C and 155H mutations. 2011 Retrovirology Result HIV Y143C 85 90 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Several substitutions, G27E, G70E, G82R, E92Q, and Q124R, were also detected in the Y143C-mutated virus, including one (E92Q) known to be associated with RAL resistance. 2011 Retrovirology Result HIV E92Q;E92Q;G27E;G70E;G82R;Q124R;Y143C 41;120;23;29;35;51;84 45;124;27;33;39;56;89 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The G140S mutant retained full activity and was as susceptible to RAL as the wild-type reference N1 enzyme (Figure 5A). 2011 Retrovirology Result HIV G140S 4 9 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The G140S/Q148R double mutant was more strongly impaired, displaying only 30% control levels of activity, and E92Q/Y143C mutant activity was barely detectable under standard conditions in vitro, indicating a functional defect. 2011 Retrovirology Result HIV E92Q;G140S;Q148R;Y143C 110;4;10;115 114;9;15;120 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The introduction of T97A into the Y143C background did not lead to detectable IN resistance in vitro (Figure 6B), ruling out a direct role for this mutation in RAL resistance. 2011 Retrovirology Result HIV T97A;Y143C 20;34 24;39 IN 78 80 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The mutant enzymes harboring the E92A/T97A/N155H (T1) and G140S/Q148R (T3) mutations retained sufficient strand transfer activity for tests of their susceptibility to RAL, whereas this was not the case for enzymes with E92Q/Y143C (T2) mutations. 2011 Retrovirology Result HIV E92A;N155H;T97A;E92Q;G140S;Q148R;Y143C 33;43;38;219;58;64;224 37;48;42;223;63;69;229 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The N155H-containing enzyme displayed about 60% the activity of the control in vitro, within the range of variation for wild-type enzymes. 2011 Retrovirology Result HIV N155H 4 9 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The N155H-mutated virus also harbored the E92A and T97A mutations known to be associated with RAL resistance. 2011 Retrovirology Result HIV E92A;N155H;T97A 42;4;51 46;9;55 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The Q148R-containing enzyme only had low levels of activity precluding precise evaluation of its resistance but preliminary studies with high protein concentrations suggested that this enzyme was not susceptible to RAL. 2011 Retrovirology Result HIV Q148R 4 9 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The recombinant enzymes harboring the N155H, Y143C, G140S and G140S/Q148R mutations were assayed for susceptibility to RAL. 2011 Retrovirology Result HIV G140S;G140S;N155H;Q148R;Y143C 52;62;38;68;45 57;67;43;73;50 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The solubility of the Y143C/N155H recombinant IN was also lower than that of the other HIV-2 INs, suggesting that proteins carrying both these mutations were unable to adopt an appropriate conformation. 2011 Retrovirology Result HIV N155H;Y143C 28;22 33;27 IN;IN 46;93 48;96 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The two B viruses differed from the EHO reference sequence by identical variations at the following residues: N17G, R34K, S56A, V72I, I84V, A129V, I133V, E146Q, T180V, I201L, L213F, T215A, R224Q, D240E and N270H. 2011 Retrovirology Result HIV A129V;D240E;E146Q;I133V;I201L;I84V;L213F;N17G;N270H;R224Q;R34K;S56A;T180V;T215A;V72I 140;196;154;147;168;134;175;110;206;189;116;122;161;182;128 145;201;159;152;173;138;180;114;211;194;120;126;166;187;132 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The two group B recombinant enzymes amplified from clinical isolates T1 and T2 at the time of virological failure contained E92A/Q mutations. 2011 Retrovirology Result HIV E92A;E92Q 124;124 130;130 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. These observations suggest that the Y143C and N155H mutations are mutually exclusive in a context of natural selection. 2011 Retrovirology Result HIV N155H;Y143C 46;36 51;41 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Thus both the N155H- and G140S/Q148R-containing enzymes were much less susceptible to RAL in vitro than the wild-type N1 HIV-2 IN, confirming that these mutations were the cause of viral resistance to RAL. 2011 Retrovirology Result HIV G140S;N155H;Q148R 25;14;31 30;19;36 IN 127 129 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Thus, the G140S and Q148R mutations play the same role in the resistance of IN to RAL as in the HIV-1 integrase. 2011 Retrovirology Result HIV G140S;Q148R 10;20 15;25 IN;IN 102;76 111;78 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. We determined whether the roles of these mutations were similar in HIV-2, by producing and purifying three recombinant IN sequences corresponding to clinical isolates T1 (N155H; R1), T2 (Y143C; R2) and T3 (G140S/Q148R; R3). 2011 Retrovirology Result HIV G140S;N155H;Q148R;Y143C 206;171;212;187 211;176;217;192 IN 119 121 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. We investigated the contribution of each individual mutation to RAL resistance, by introducing G140S, Q148R, N155H and Y143C single mutations and the G140S/Q148R double mutation into the HIV-2 wild-type IN N1 sequence by site-directed mutagenesis. 2011 Retrovirology Result HIV G140S;G140S;N155H;Q148R;Q148R;Y143C 95;150;109;102;156;119 100;155;114;107;161;124 IN 203 205 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. We investigated the role of the E92 mutation by preparing the E92Q single mutant and the E92Q/Y143C double mutant in the wild-type N1 background. 2011 Retrovirology Result HIV E92Q;E92Q;Y143C 62;89;94 66;93;99 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. We tested this hypothesis, by producing a T97A-containing IN. 2011 Retrovirology Result HIV T97A 42 46 IN 58 60 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. As a control, the A182T mutant of RAV-1 IN CCD (termed RAV-1 IN CCDA182T), corresponding to the RSV-A IN CCD sequence, was purified and the crystallization conditions for both RAV-1 IN CCD and RSV-A IN CCD were tested; that is, a MES buffer at pH 6.0 and a citrate buffer at pH 6.2, respectively. 2011 PloS one Result HIV A182T 18 23 IN;IN;IN;IN;IN 40;61;102;182;199 42;63;104;184;201 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. The A182T substitution mostly affects the side-chain orientation of the neighboring Arg179 of the alpha4-alpha5 loop. 2011 PloS one Result HIV A182T 4 9 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. The A182T substitution, which also occurs between the Schmidt-Ruppin strains B and A of RSV IN, does not affect the tertiary structure of avian INs. 2011 PloS one Result HIV A182T 4 9 IN;IN 92;144 94;147 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. The H103C mutant. 2011 PloS one Result HIV H103C 4 9 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. This fragment differs by a single residue from the CCD of RSV-A IN (A182T substitution), for which numerous crystal structures have been solved. 2011 PloS one Result HIV A182T 68 73 IN 64 66 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. Thus, the A182T substitution influences crystal assembly via Arg179 and, either large tetragonal crystals or tiny hexagonal microcrystals are observed for RAV-1 IN CCDA182T, whereas only hexagonal crystals are obtained for RAV-1 IN CCD. 2011 PloS one Result HIV A182T 10 15 IN;IN 161;229 163;231 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Accordingly, the mechanisms by which N348I decreases RT RNase H activity and drug susceptibility cannot be inferred from this structure. 2011 Retrovirology Result HIV N348I 37 42 RT 53 55 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Accordingly, we generated by site directed mutagenesis six HIV-1 RT constructs that contained the N348I, N348A, N348Q, N348L, N348E or N348R mutations. 2011 Retrovirology Result HIV N348A;N348E;N348I;N348L;N348Q;N348R 105;126;98;119;112;135 110;131;103;124;117;140 RT 65 67 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. As predicted by the molecular modelling studies, the N348A and N348Q mutations had minimal impact on the ATP-mediated excision activity of the enzyme (Figures 3A, B). 2011 Retrovirology Result HIV N348A;N348Q 53;63 58;68 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. As reported previously, N348I significantly reduced the frequency of a polymerase-independent cleavage event that decreases the RNA/DNA duplex to 10 nucleotides (Figure 4B). 2011 Retrovirology Result HIV N348I 24 29 Pol 71 81 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. As such, their enzyme preparations may have been contaminated by p66N348I/p51N348I RT generated by bacterial proteases, thus complicating data analysis. 2011 Retrovirology Result HIV N348I 68 73 PR;RT 109;83 118;85 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Because the p66 subunit of RT can be cleaved to p51 by bacterial proteases, one cannot exclude the possibility that the purified enzymes prepared by Schuckman and co-workers were not contaminated by p66N348I/p51N348I HIV-1 RT. 2011 Retrovirology Result HIV N348I 202 207 PR;RT;RT 65;27;223 74;29;225 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. By contrast, the N348A and N348Q enzymes retained near WT-like RNase H cleavage activities. 2011 Retrovirology Result HIV N348A;N348Q 17;27 22;32 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. By contrast, the polymerase activities of the N348E and N348R RTs were decreased significantly compared to the WT enzyme, and accordingly they were excluded from subsequent analyses. 2011 Retrovirology Result HIV N348E;N348R 46;56 51;61 Pol;RT 17;62 27;65 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. By contrast, when N348L was present in p51 only, HIV-1 RT exhibited 5.7-fold nevirapine resistance. 2011 Retrovirology Result HIV N348L 18 23 RT 55 57 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. By contrast, when N348L was present in the p51 subunit only, the mutant enzyme exhibited robust AZT-MP excision activity (Figure 3B). 2011 Retrovirology Result HIV N348L 18 23 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. By contrast, when N348L was present only in the p51 subunit, the mutant enzyme showed an RNase H phenotype similar to the enzyme that contained the N348L mutation in both subunits (Figure 4B, C). 2011 Retrovirology Result HIV N348L;N348L 18;148 23;153 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Consistent with the observed increase in AZT-MP excision activity, the N348L mutation also significantly decreased the frequency of this polymerase-independent cleavage event. 2011 Retrovirology Result HIV N348L 71 76 Pol 137 147 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Furthermore, they reported approximately ~ 2-2.7 -fold resistance when the N348I mutation was present in both subunits; ~ 1.9-2-fold when present in p66 only; and 2.7-3.1-fold when present in p51 only (see Table three in). 2011 Retrovirology Result HIV N348I 75 80 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. However, it should be noted that HIV-1 RTs that contained the N348I and N348L mutations showed fold-changes in nevirapine resistance (8.6- and 11.4-fold, respectively) that were greater than those calculated for the N348A (3.4-fold) or N348Q (2.4-fold) HIV-1 RTs. 2011 Retrovirology Result HIV N348A;N348I;N348L;N348Q 216;62;72;236 221;67;77;241 RT;RT 39;259 42;262 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. However, the N348A and N348Q mutations also yielded nevirapine resistance. 2011 Retrovirology Result HIV N348A;N348Q 13;23 18;28 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. However, when N348I was present only in the p66 subunit, the mutant enzyme exhibited AZT-MP excision activity that was similar to the WT RT (Figure 3B). 2011 Retrovirology Result HIV N348I 14 19 RT 137 139 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. If nevirapine resistance was due to the mutation in both subunits, one would expect a higher fold-resistance for the p66N348I/p51N348I RT compared to the p66N348I/p51WT or p66WT/p51N348I enzymes. 2011 Retrovirology Result HIV N348I;N348I;N348I 120;157;181 125;162;186 RT 135 137 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. In this regard, we successfully purified the p66N348I/p51WT, p66N348A/p51WT, p66N348Q/p51WT and p66WT/p51N348L enzymes. 2011 Retrovirology Result HIV N348A;N348L;N348Q 64;105;80 69;110;85 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Interestingly, previous studies have demonstrated that N348I confers nevirapine resistance on both RNA/DNA and DNA/DNA T/P substrates, suggesting that factors in addition to RNase H cleavage impact nevirapine binding. 2011 Retrovirology Result HIV N348I 55 60 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Interestingly, when the N348A, N348Q or N348I mutations were present in the p66 subunit only, RT susceptibility to nevirapine was similar to that of the WT enzyme (Table 1). 2011 Retrovirology Result HIV N348A;N348I;N348Q 24;40;31 29;45;36 RT 94 96 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Interestingly, when the N348I mutation was present only in the p66 subunit, the observed RNase H cleavage pattern was similar to that of the WT enzyme (Figure 4C). 2011 Retrovirology Result HIV N348I 24 29 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. It should be noted, however, that the fold-change in nevirapine resistance was lower for the p66WT/p51N348L RT (5.7-fold) compared to p66N348L/p51N348L RT (11.4-fold). 2011 Retrovirology Result HIV N348L;N348L 102;137 107;142 RT;RT 108;152 110;154 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. N348I and N348L) also confer the highest levels of nevirapine resistance, thus providing additional support for a link between RNase H cleavage and NNRTI resistance. 2011 Retrovirology Result HIV N348L;N348I 10;0 15;5 NNRTI 148 153 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Our results show that the N348A, N348I, N348Q and N348L mutations confer nevirapine resistance when present in both the p66 and p51 subunits of HIV-1 RT. 2011 Retrovirology Result HIV N348A;N348I;N348L;N348Q 26;33;50;40 31;38;55;45 RT 150 152 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Previous biochemical studies demonstrated that N348I in HIV-1 RT indirectly increases AZT resistance by decreasing the frequency of secondary RNase H cleavages that significantly reduce the RNA/DNA duplex length of the T/P and diminish the efficiency of AZT-MP excision. 2011 Retrovirology Result HIV N348I 47 52 RT 62 64 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. reported that the N348I mutation in either subunit caused nevirapine resistance. 2011 Retrovirology Result HIV N348I 18 23 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Taken together, these data show that the N348I or N348L mutations in the p51 subunit of HIV-1 RT are responsible for the observed decreased RNase H cleavage and increased AZT-MP excision phenotypes. 2011 Retrovirology Result HIV N348I;N348L 41;50 46;55 RT 94 96 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Taken together, these modelling studies suggest that the N348I mutation in the context of the p51 subunit of HIV-1 RT may decrease the enzyme's RNase H activity via an altered interaction with the RNA template. 2011 Retrovirology Result HIV N348I 57 62 RT 115 117 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. The DNA polymerase activities of N348A, N348I, N348L and N348Q were found to be similar to that of the WT enzyme. 2011 Retrovirology Result HIV N348A;N348I;N348L;N348Q 33;40;47;57 38;45;52;62 Pol 8 18 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. The repositioning of this loop in the N348I RT is likely due to the bulky side-chain of isoleucine disrupting the network of interactions between this residue and Y342. 2011 Retrovirology Result HIV N348I 38 43 RT 44 46 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. When the N348I mutation is introduced into the p51 subunit in this structure by molecular modelling (Figure 1D), the position of the beta14-beta15 loop is shifted such that P345 and F346 no longer contact the RNA template. 2011 Retrovirology Result HIV N348I 9 14 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. who also reported that the N348I mutant in the p51 subunit conferred the decreased RNase H/increased AZT-MP excision phenotype. 2011 Retrovirology Result HIV N348I 27 32 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Again, mutations A364V and V370A conferred > 150-fold resistance but, interestingly, mutations V362I and S368N, which demonstrated only low-level resistance in the background of HXB2 and PR-1, also resulted in the fully resistant phenotype when introduced in PR-2 (see Additional file 2, compare panels C and E with D and F). 2011 Retrovirology Result HIV A364V;S368N;V362I;V370A 17;105;95;27 22;110;100;32 PR;PR 187;259 189;261 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Although the absolute cleavage efficiency of PR-2 was lower compared to HXB2, the relative increase in processing caused by adding mutation V362I or A364V was approximately 50% greater for the PR-2 protease than for the HXB2 protease (Table 6). 2011 Retrovirology Result HIV A364V;V362I 149;140 154;145 PR;PR;PR;PR 198;225;45;193 206;233;47;195 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. For both proteases, processing of the peptide with mutation A364V was one order of magnitude faster compared to V362I. 2011 Retrovirology Result HIV A364V;V362I 60;112 65;117 PR 9 18 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In all 58 isolates at least one of the following mutations was found: Gag V362I, A364V, S368N or V370A/L. 2011 Retrovirology Result HIV A364V;S368N;V362I;V370A;V370L 81;88;74;97;97 86;93;79;104;104 Gag 70 73 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In contrast to viruses with WT proteases, viruses with PI resistant proteases (PR-1 - PR-6) showed a much more diverse resistance pattern (Table 3) with a significantly higher prevalence of mutations at position 362, 368 and in the QVT-motif (V370A/L and T371N, Table 4). 2011 Retrovirology Result HIV T371N;V370A;V370L 255;243;243 260;251;251 PR;PR;PI;PR;PR 31;68;55;79;86 40;77;57;81;88 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In summary, we identified 8 bevirimat resistance mutations at 7 different codons: V362I, L363M, A364V, A366V, S368N, V370A/L and T371N. 2011 Retrovirology Result HIV A364V;A366V;L363M;S368N;T371N;V362I;V370A;V370L 96;103;89;110;129;82;117;117 101;108;94;115;134;87;124;124 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In the two cultures where A364V was not selected, mutations V362I and V370A were observed respectively. 2011 Retrovirology Result HIV A364V;V362I;V370A 26;60;70 31;65;75 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In wild-type HXB2, mutations A364V and V370A conferred the highest level of resistance (Table 5). 2011 Retrovirology Result HIV A364V;V370A 29;39 34;44 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Mutation A364V was highly detrimental in this background and reduced viral replication to a minimum. 2011 Retrovirology Result HIV A364V 9 14 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Mutations S368N and V370A had a more severe impact resulting in intermediate replication levels. 2011 Retrovirology Result HIV S368N;V370A 10;20 15;25 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Mutations V362I and S368N resulted in low-level resistance (2.8-fold and 6.6-fold respectively). 2011 Retrovirology Result HIV S368N;V362I 20;10 25;15 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Nonapeptides representing the WT CA/p2 cleavage site, or containing bevirimat resistance mutation V362I or A364V, were processed with either the HXB2 or the PR-2 protease enzyme. 2011 Retrovirology Result HIV A364V;V362I 107;98 112;103 PR;Capsid;PR 162;33;157 170;35;159 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. The effect of mutations V362I and A364V on CA/p2 processing was analyzed in the background of HXB2 and PR-2 proteases. 2011 Retrovirology Result HIV A364V;V362I 34;24 39;29 PR;Capsid;PR 108;43;103 117;45;105 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Therefore we introduced Gag mutations V362I, A364V, S368N or V370A by site-directed mutagenesis in the background of HXB2, PR-1 and PR-2. 2011 Retrovirology Result HIV A364V;S368N;V362I;V370A 45;52;38;61 50;57;43;66 Gag;PR;PR 24;123;132 27;125;134 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. This revealed that the newly identified S368N mutation indeed is a bevirimat resistance mutation, which results in low-level resistance in a wild-type protease background but can give high-level resistance in the context of a mutated protease. 2011 Retrovirology Result HIV S368N 40 45 PR;PR 151;234 159;242 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. This was confirmed by clonal analysis of one culture containing multiple mutations (culture HXB2 #8; V362I+A364V, data not shown). 2011 Retrovirology Result HIV A364V;V362I 107;101 112;106 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Viruses with wild-type proteases (HXB2, NL4-3 and NC/p1 variants) selected for Gag mutation A364V in 26 of 28 cultures, with additional mutations observed in 4 of these 26: two cultures had V362I+A364V; one had A366V+A364V and another one V370A+A364V (Table 2). 2011 Retrovirology Result HIV A364V;A364V;A364V;A364V;A366V;V362I;V370A 92;196;217;245;211;190;239 97;201;222;250;216;195;244 PR;Gag;NC 23;79;50 32;82;52 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. However, only patient SE59 had the major mutation L90M (1/28; 3.5%). 2011 Virology journal Result HIV L90M 50 54 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Minor mutations or polymorphisms in RT were observed in patients SE71, SE91 and SE111 i.e.: V118I, E138A, and V90I mutations respectively. 2011 Virology journal Result HIV E138A;V118I;V90I 99;92;110 104;97;114 RT 36 38 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Patient SE34, in treatment interruption, had L100I mutation associated with NNRTI resistance, and finally patient SE60, receiving HAART, had the NNRTI resistance mutation K103N. 2011 Virology journal Result HIV K103N;L100I 171;45 176;50 NNRTI;NNRTI 76;145 81;150 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Patient SE37, naive for antiretroviral treatment, had A98G and K70R major mutations associated with resistance to non-nucleoside RT inhibitors (NNRTI), and nucleoside RT inhibitors (NRTI), respectively. 2011 Virology journal Result HIV A98G;K70R 54;63 58;67 NNRTI;NRTI;RT;RT 144;182;129;167 149;186;131;169 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. The M36I mutation in protease was observed in all patients, whilst K20I/R, L63P, V77I and L10V/I mutations were present in 75%, 17.8%, 10.7% and 7.1% of patients, respectively. 2011 Virology journal Result HIV K20I;K20R;L10I;L10V;L63P;M36I;V77I 67;67;90;90;75;4;81 73;73;96;96;79;8;85 PR 21 29 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. A different intracellular distribution of wild type and N74D CA was also observed by immunofluorescence (Figure S5). 2011 PLoS pathogens Result HIV N74D 56 60 Capsid 61 63 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. In contrast, the N74D CA mutant was not found accumulating into the nuclei of either control or Tnp3 KD cells (Figure 11F). 2011 PLoS pathogens Result HIV N74D 17 21 Capsid 22 24 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Intriguingly, swapping the G2 anticodon sequence from lysine to aspartate (m22) inhibited tRNA binding to Tnp3 but swapping to glutamate (m20) did not (Figure 6 and Table 1). 2011 PLoS pathogens Result HIV K22D 54 79 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Of all mutant vectors the N74D was the least dependent on Tnp3 for infection and maintained normal infectivity (Figure 10). 2011 PLoS pathogens Result HIV N74D 26 30 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The A105S mutant vector maintained near-wild type infectivity and was also clearly less dependent on Tnp3 for infection. 2011 PLoS pathogens Result HIV A105S 4 9 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The biological significance of this result was confirmed using an HIV-1 vector bearing the N74D mutation in CA, which is the least dependent on Tnp3 for infection (Figure 11B, 11C). 2011 PLoS pathogens Result HIV N74D 91 95 Capsid 108 110 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The N74D mutant virus did not appear to accumulate CA in the nuclei in either control or Tnp3 KD cells (Figure 11B). 2011 PLoS pathogens Result HIV N74D 4 8 Capsid 51 53 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The N74D point mutant, which is independent of Tnp3 for infection was tested in parallel. 2011 PLoS pathogens Result HIV N74D 4 8 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The ratio of nuclear to cytoplasmic CA was significantly higher in KD than control cells infected with wild type virus but remained essentially unchanged in cells infected with the N74D mutant (Figure 11D). 2011 PLoS pathogens Result HIV N74D 181 185 Capsid 36 38 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The T54A and the T54A/N57A capsid mutant HIV-1 vectors showed substantially reduced infectivity compared to wild type virus, however they were also less dependent on Tnp3 for infection (Figure 10). 2011 PLoS pathogens Result HIV N57A;T54A;T54A 22;4;17 26;8;21 Capsid 27 33 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. We also tested the A105S mutation, which conferred resistance to the antiretroviral compound Coumermycin-A1. 2011 PLoS pathogens Result HIV A105S 19 24 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Assuming that the resistance index of the compounds 17-19 against K103N + Y181C HIV-1 strain is 50-200 as was shown for benzophenones 20, 24, and 25, they should display antiviral activity against this strain at micromolar concentrations, that is, in the same range as they tend to precipitate. 2011 Bioorganic & medicinal chemistry Result HIV K103N;Y181C 66;74 71;79 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Both benzophenones 17 and 20 retained activity against most HIV-RT forms with the exception of V106A (Table 3). 2011 Bioorganic & medicinal chemistry Result HIV V106A 95 100 RT 64 66 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Both compounds proved to be inactive against the V106A RT, while efavirenz retained activity. 2011 Bioorganic & medicinal chemistry Result HIV V106A 49 54 RT 55 57 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Compounds 11-22 and 24-25 were also evaluated against a drug-resistant (double mutant) HIV-1 strain bearing the K103N and Y181C mutations in the RT. 2011 Bioorganic & medicinal chemistry Result HIV K103N;Y181C 112;122 117;127 RT 145 147 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. For example, nevirapine and efavirenz exhibited a 15-fold and 10-fold lower activity, respectively, towards the L100I RT mutant compared to the wild-type enzyme, whereas benzophenones 17 and 20 retained almost full activity, exhibiting only a very minor degree of resistance (1.4-fold and 2.5-fold, respectively). 2011 Bioorganic & medicinal chemistry Result HIV L100I 112 117 RT 118 120 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. For the Y181C RT mutant, compounds 17 and 20 inhibited the polymerase 3.3- and 2-fold less effectively, as compared to a decrease of 395- and 2.6-fold for nevirapine and efavirenz, respectively. 2011 Bioorganic & medicinal chemistry Result HIV Y181C 8 13 Pol;RT 59;14 69;16 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. In that regard, compounds 17 and 20 both exhibited the highest activity against the wild-type virus but exhibited quite different levels of activity towards the K103N/Y181C double mutant HIV-1 strain (Table 3 ). 2011 Bioorganic & medicinal chemistry Result HIV K103N;Y181C 161;167 166;172 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. In the case of the Y188L mutant RT, the activity of benzophenone 17 was 4.3-fold lower than for the wild-type enzyme, while compound 20 exhibited 12-fold lower activity. 2011 Bioorganic & medicinal chemistry Result HIV Y188L 19 24 RT 32 34 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Interestingly, benzophenone 17 displayed even higher inhibitory activity toward the mutant G190A RT form, while 20 exhibited somewhat lower activity (2.3-fold), more closely in line with efavirenz (2.7-fold decrease) but in sharp contrast to nevirapine (423-fold decrease). 2011 Bioorganic & medicinal chemistry Result HIV G190A 91 96 RT 97 99 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Lastly, benzophenones 17 and 20, as well as efavirenz, exhibited a 23.8-, 14.9- and 19.3-fold lower efficacy towards the K103N/Y181C double mutant RT, as compared to a >250-fold lower inhibitory activity for nevirapine. 2011 Bioorganic & medicinal chemistry Result HIV K103N;Y181C 121;127 126;132 RT 147 149 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Moreover, the resistance index for the compounds against the Y181C, Y188L and K103N/Y181C mutant RTs was comparable to that of efavirenz, and even lower for the L100I, K103N and G190A mutants, although for the V106A mutant, efavirenz was more potent than 17 and 20. 2011 Bioorganic & medicinal chemistry Result HIV G190A;K103N;K103N;L100I;V106A;Y181C;Y181C;Y188L 178;78;168;161;210;61;84;68 183;83;173;166;215;66;89;73 RT 97 100 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Next, in order to more fully understand the activity of the benzophenones against drug-resistant HIV strains as well as to verify the reasons for the poor levels of activity of the compounds against the K103N/Y181C RT double mutant virus, a panel of RT's bearing one or two of the most clinically significant mutations (L100I, K103N, V106I, Y181C, Y188L, G190A, and K103N/Y181C) conferring resistance of the virus to NNRTIs was constructed. 2011 Bioorganic & medicinal chemistry Result HIV G190A;K103N;K103N;K103N;L100I;V106I;Y181C;Y181C;Y181C;Y188L 355;203;327;366;320;334;209;341;372;348 360;208;332;371;325;339;214;346;377;353 NNRTI;RT;RT 417;215;250 423;217;252 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Similarly, against K103N, a common drug-resistant HIV-RT form, the inhibitory activity of nevirapine was 400-fold lower than that towards wtRT, whereas activity of efavirenz or the studied benzophenones 17 and 20 was only 24-, 13.8 and 8-fold lower, respectively. 2011 Bioorganic & medicinal chemistry Result HIV K103N 19 24 RT;RT 54;140 56;142 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. The anti-HIV properties of the uracil derivatives were studied in human T-lymphocyte CEM (compounds 6-10) or MT-4 (compounds 11-26) cell cultures infected with HIV-1(IIIB) or HIV-2 (ROD), or the double mutant (K103N + Y181C RT) virus strain (Table 1 ). 2011 Bioorganic & medicinal chemistry Result HIV K103N;Y181C 210;218 216;223 RT 224 226 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. An M184V mutation at this position in HIV-1 RT causes strong, steric hindrance-based, resistance to 3TC and FTC, and to a lesser extent to ddI, ABC [reviewed in ], and translocation defective RT inhibitors (TDRTIs) (Table 1). 2012 Nucleic acids research Result HIV M184V 3 8 RT;RT 44;192 46;194 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. Another HIV-1 RT mutation, K65R, decreases susceptibility to tenofovir. 2012 Nucleic acids research Result HIV K65R 27 31 RT 14 16 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. Interestingly, Q190M XMRV RT has a decreased susceptibility to AZT (approximately 5-fold increase in the IC50). 2012 Nucleic acids research Result HIV Q190M 15 20 RT 26 28 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. Similarly, the K103R XMRV RT mutant enzyme was less susceptible to tenofovir, increasing the IC50 by at least 2-fold. 2012 Nucleic acids research Result HIV K103R 15 20 RT 26 28 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. Similarly, the M41L mutation, which causes excision-based AZT resistance in HIV is already present in XMRV and MoMLV RT (L81, Table 1). 2012 Nucleic acids research Result HIV M41L 15 19 RT 117 119 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. Since AZT and tenofovir are potent inhibitors of XMRV (Table 6), we wanted to investigate whether the XMRV RT mutant equivalents of HIV Q151M and K65R (XMRV Q190M and K103R) would confer XMRV RT resistance to AZT and tenofovir. 2012 Nucleic acids research Result HIV K65R;Q151M;K103R;Q190M 146;136;167;157 150;141;172;162 RT;RT 107;192 109;194 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. The HIV-1 RT mutation Q151M confers resistance to AZT by enhancing discrimination of the nucleotide analog leading to its reduced incorporation. 2012 Nucleic acids research Result HIV Q151M 22 27 RT 10 12 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. At these positions, the major polymorphisms found were N161H, Y154H, I197M, K201N/I/E and K208E/R/G. 2011 PloS one Result HIV I197M;K201E;K201I;K201N;K208E;K208G;K208R;N161H;Y154H 69;76;76;76;90;90;90;55;62 74;85;85;85;99;99;99;60;67 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. We carried out in triplicate experiments comparing the wild-type human ITGA4 gene with the quintuple mutant Y154H/N161H/I197M/ K201I/K208G, which contains the most frequent polymorphisms found among Platyrrhini, and is characteristic of the Callithrix, Cebuella and Mico genera. 2011 PloS one Result HIV I197M;N161H;Y154H;K201I;K208G 120;114;108;127;133 125;119;113;132;138 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. Whereas both substitutions in the coding sequence of exon 5 (positions 154 and 161) and the I197M substitution in exon 6 did not involve a change the electrostatic charge, K201I and K208G in exon 6 did involve the loss of a positively-charged amino acid, resulting in change in the local electrostatic environment in this region of alpha4. 2011 PloS one Result HIV I197M;K201I;K208G 92;172;182 97;177;187 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Finally 14/38 (37%) had >=4 mutations: 13/14 (93%) M184V/I and 8/14 (57%) K103N, all with >=2 NNRTI and most with one or more thymidine analogue mutations (TAM) or other NRTI mutations. 2011 Journal of AIDS & clinical research Result HIV K103N;M184I;M184V 74;51;51 79;58;58 NNRTI;NRTI 94;170 99;174 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. However, the remaining six patients who were re-suppressed had NNRTI DRM, three had K103N, one had K103N and M184V and one had K103N, V106M and M184V (Table 4b). 2011 Journal of AIDS & clinical research Result HIV K103N;K103N;K103N;M184V;M184V;V106M 84;99;127;109;144;134 89;104;132;114;149;139 NNRTI 63 68 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Of the genotyped samples 5/38 (13%) had K103N alone; 2/38 (5%) had M184V and K103N; and 10/38 (26%) had three mutations with M184V/I, K103N and an additional NNRTI mutation. 2011 Journal of AIDS & clinical research Result HIV K103N;K103N;K103N;M184I;M184V;M184V 40;77;134;125;67;125 45;82;139;132;72;132 NNRTI 158 163 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Overall, 8/38 (21%) had one or more TAMs, three had A62V or V75I and only one patient had K65R. 2011 Journal of AIDS & clinical research Result HIV A62V;K65R;V75I 52;90;60 56;94;64 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. As similar results were obtained with the two mutant gp120 complexes, only sera from mice immunized with the N448Q complex were tested and compared with sera from animals immunized with the wild type complex. 2011 Vaccine Result HIV N448Q 109 114 gp120 53 58 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. C57BL/6 and BALB/c mice were primed intramuscularly with DNA encoding gp120 with the N448Q mutation or the wild type sequence and then boosted twice, three weeks apart, via a subcutaneous injection with the corresponding mutated or wild type gp120 proteins in the presence of adjuvant QS21. 2011 Vaccine Result HIV N448Q 85 90 gp120;gp120 70;242 75;247 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Due to the limited availability of the specimen, sera from the N448E complex-immunized mice were not used in this experiment. 2011 Vaccine Result HIV N448E 63 68 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Half maximal anti-gp120 Ab titers of 1:12,000 and 1:2,500 were elicited by N448Q gp120/654 complex and N448Q gp120 DNA prime/protein boost, respectively. 2011 Vaccine Result HIV N448Q;N448Q 75;103 80;108 gp120;gp120;gp120 18;81;109 23;86;114 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Higher reactivity to V3 was observed with N448Q as compared to wild type gp120 in their uncomplexed forms, but V3 reactivity was further enhanced in the N448Q/654 complex (p <0.05 at the lowest dilution vs. 2011 Vaccine Result HIV N448Q;N448Q 42;153 47;158 gp120 73 78 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. However, anti-V3 Abs were not detected in the sera of mice immunized with either wild type or mutant gp120s (Figure 1B), indicating that the enhanced V3 antigenicity demonstrated by N448Q gp120 in-vitro was not sufficient to augment its immunogenicity upon vaccination. 2011 Vaccine Result HIV N448Q 182 187 gp120;gp120 101;188 107;193 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. In contrast, V2 reactivity was lower against the wild type and N448Q complexes as compared to the respective gp120s (Figure 5C). 2011 Vaccine Result HIV N448Q 63 68 gp120 109 115 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Increased antigenicity and stability of the C2 epitope were displayed most in the N448Q/654 complex, and corresponded with the higher level of anti-C2 Abs induced by immunization with the N448Q/654 complex (Figure 3B). 2011 Vaccine Result HIV N448Q;N448Q 82;188 87;193 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Interestingly, higher lymphoproliferation was achieved following immunization with the N448Q gp120 than that with the wild type gp120. 2011 Vaccine Result HIV N448Q 87 92 gp120;gp120 93;128 98;133 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Lymphoproliferative responses to both peptides were significantly higher in mice immunized with N448Q than in mice with wild type gp120. 2011 Vaccine Result HIV N448Q 96 101 gp120 130 135 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Moreover, the C2 epitope was more resistant to cathepsin L in context of the N448Q complex than in the wild type gp120 complex. 2011 Vaccine Result HIV N448Q 77 82 gp120 113 118 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Moreover, the immune complexes displayed enhanced anti-C2 reactivity as compared to the respective uncomplexed gp120s, and the increase was greater with the N448Q complex (p<0.001 vs. 2011 Vaccine Result HIV N448Q 157 162 gp120 111 117 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Nevertheless, V3 reactivity was preserved better in context of the N448Q gp120/654 complex than in the wild type complex (p <0.001). 2011 Vaccine Result HIV N448Q 67 72 gp120 73 78 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Next, we evaluated whether the N448Q mutation had any effect on T cell responses against gp120. 2011 Vaccine Result HIV N448Q 31 36 gp120 89 94 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Of note, this C2 epitope was also most accessible for Ab binding on the N448Q/654 complex (Figure 5B). 2011 Vaccine Result HIV N448Q 72 77 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Peptides 40 and 41 also elicited higher production of Th2-associated cytokines IL-10 and IL-6, respectively (p<0.001), while secretion of Th1 cytokine IFN-gamma in response to these peptides was significantly reduced when the mice were immunized with N448Q as compared to wild type gp120. 2011 Vaccine Result HIV N448Q 251 256 gp120 282 287 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Significantly, the complexes with N448Q or N448E elicited even more potent neutralizing activity, with IC50 titers reaching up to 1:170. 2011 Vaccine Result HIV N448E;N448Q 43;34 48;39 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Similar results were observed with the V3 epitope in context of the N448Q/654 complex, albeit at lower extents. 2011 Vaccine Result HIV N448Q 68 73 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. The data demonstrate that digestion of wild type and N448Q gp120 with cathepsin L reduced V3 reactivity by 40-60% (Figure 6A, left panel). 2011 Vaccine Result HIV N448Q 53 58 gp120 59 64 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. The data in Figure 3B show that sera from the N448Q complex-immunized mice displayed significantly higher Ab reactivity against four of the peptides pools as compared to sera from mice receiving the wild type gp120 complex, with the greatest differences observed with peptide pools representing the C1 and C2 regions in the inner domain of gp120 (C1:6-10 and C2:21-25; p <0.001). 2011 Vaccine Result HIV N448Q 46 51 gp120;gp120 209;340 214;345 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. The N448Q complex also had a slightly higher level of V3 reactivity than the wild type complex but the difference was not significant. 2011 Vaccine Result HIV N448Q 4 9 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. The V3 peptide treatment of sera from the N448Q complex-immunized animals reduced the neutralizing activity by approximately 25%, with IC50 remaining at 1:70 (Figure 4C). 2011 Vaccine Result HIV N448Q 42 47 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. There was a trend of higher anti-gp120 and anti-V3 Ab titers elicited by the N448Q complex and the N448E complex as compared to the wild type gp120 complex, but the differences did not reach statistical significance. 2011 Vaccine Result HIV N448E;N448Q 99;77 104;82 gp120;gp120 33;142 38;147 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. To assess whether the neutralizing activity observed in sera from the N448Q complex-immunized mice was also mediated in part by Abs to C1 and C2 that were induced to higher levels by the N448Q complex (Figure 3B), the sera was pre-treated with peptides encompassing the C1 and C2 regions (C1:6-10 and C2:21-25, respectively) and then tested in the neutralization assay. 2011 Vaccine Result HIV N448Q;N448Q 70;187 75;192 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. To investigate whether the higher anti-gp120 T cell response observed in mice immunized with the N448Q mutant was due to alterations in T cell recognition of epitopes around position 448, T cell response to two overlapping peptides representing the wild type gp120 sequence from positions 421 to 440 (peptide 40) and from positions 432 to 450 (peptide 41) were analyzed (Figure 2B). 2011 Vaccine Result HIV N448Q 97 102 gp120;gp120 39;259 44;264 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. To test this idea, we compared the reactivity of uncomplexed N448Q versus the N448Q/mAb 654 complex with mAbs against V3 (694), C2 (1006), and V2 (697) in ELISA. 2011 Vaccine Result HIV N448Q;N448Q 61;78 66;83 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Two different mutations that remove the N448-linked glycan, N448Q and N448E, were tested for comparison. 2011 Vaccine Result HIV N448E;N448Q 70;60 75;65 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. uncomplexed N448Q) (Figure 5A). 2011 Vaccine Result HIV N448Q 12 17 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Unlike that with V3 peptide, pre-treatment with the C1 and C2 peptides had no effect on neutralizing activity (Figure 4D), indicating that the enhanced Ab response induced against the C1 and C2 peptides by the N448Q complex has no virus-neutralizing activity. 2011 Vaccine Result HIV N448Q 210 215 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. When BALB/c mice were immunized with wild type or N448Q gp120s using the same DNA prime/protein boost protocol, the N448Q gp120 also elicited similar levels of anti-gp120 serum IgG as the wild type, although the mutant stimulated lower levels of anti-gp120 IgG1 (Supplementary Figure 1). 2011 Vaccine Result HIV N448Q;N448Q 50;116 55;121 gp120;gp120;gp120;gp120 56;122;165;251 62;127;170;256 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Wild type gp120 and the N448Q mutant were tested as uncomplexed antigens and as immune complexes with mAb 654. 2011 Vaccine Result HIV N448Q 24 29 gp120 10 15 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. Amino acid alignment of the PR gene showed that the test consensus was identical to the global subtype C consensus, except at position T13I. 2011 Journal of health, population, and nutrition Result HIV T13I 135 139 PR 28 30 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. Futhermore, this sample harboured the only D67G NRTI mutation observed in the study. 2011 Journal of health, population, and nutrition Result HIV D67G 43 47 NRTI 48 52 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. It differed from the global subtype B consensus at 18 positions (V35T, E36A, T39E, S48T, K122E, D123G, K173A, D177E, T200A, Q207E, R211K, V245Q, A272P, K277R, T286A, E291D, V292I, and I293V). 2011 Journal of health, population, and nutrition Result HIV A272P;D123G;D177E;E291D;E36A;I293V;K122E;K173A;K277R;Q207E;R211K;S48T;T200A;T286A;T39E;V245Q;V292I;V35T 145;96;110;166;71;184;89;103;152;124;131;83;117;159;77;138;173;65 150;101;115;171;75;189;94;108;157;129;136;87;122;164;81;143;178;69 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. It differed from the global subtype B consensus at eight positions (T12S, I15V, L19I, M36I, R41K, H69K, L89M, and I93L). 2011 Journal of health, population, and nutrition Result HIV H69K;I15V;I93L;L19I;L89M;M36I;R41K;T12S 98;74;114;80;104;86;92;68 102;78;118;84;108;90;96;72 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. These included four NRTI mutations (D67E, D67G, T69D, and T215Y) harboured by sequences 08MB38ZA, 08MB26ZA, 08MB27ZA, and 08MB29ZA respectively, and one PI resistance mutation (M46I) observed in sequence 08MB62ZA. 2011 Journal of health, population, and nutrition Result HIV D67E;D67G;M46I;T215Y;T69D 36;42;177;58;48 40;46;181;63;52 NRTI;PI 20;153 24;155 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. 3a), although we note that EC50 values for the Y143C variant were on average 3.5-fold higher than the corresponding values for wild-type ROD9 (range = 1.7-6.1-fold higher, n = 4), potentially reflecting a low level of raltegravir resistance. 2011 AIDS (London, England) Result HIV Y143C 47 52 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. A similar level of resistance (15-fold) was observed for N155H HIV-1. 2011 AIDS (London, England) Result HIV N155H 57 62 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Although this particular genotype has not been observed in patient-derived HIV-1 or HIV-2 sequences, we sought to determine whether the combined effects of Q148R and N155H imparted higher levels of raltegravir resistance relative to the corresponding single amino acid changes. 2011 AIDS (London, England) Result HIV N155H;Q148R 166;156 171;161 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. In agreement with a previous report suggesting that the N155H change impairs HIV-2 replication capacity, plasmids encoding N155H HIV-2 ROD9 produced titers of infectious progeny that, on average, were 3.7-fold lower than the parental wild-type construct. 2011 AIDS (London, England) Result HIV N155H;N155H 56;123 61;128 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. In comparison, a site-directed mutant of HIV-1 NL4-3 encoding the N155H integrase replacement, which we constructed as a known raltegravir-resistant control for our assays, exhibited 15-fold resistance to the drug (EC50 = 73 +- 34 nmol/l. 2011 AIDS (London, England) Result HIV N155H 66 71 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. In contrast, Q148R and N155H variants of HIV-2 ROD9 were both significantly resistant to raltegravir, with EC50 values of 130 +- 12 and 66 +- 31 nmol/l (14-fold and 7.0-fold higher than wild-type ROD9, respectively). 2011 AIDS (London, England) Result HIV N155H;Q148R 23;13 28;18 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Q148R with N155H HIV-2 yielded the lowest level of infectious virus of all the mutants tested; the average titer for the double mutant was 53-fold lower than that of wild-type ROD9. 2011 AIDS (London, England) Result HIV N155H;Q148R 11;0 16;5 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Strikingly, the combination of Q148R with N155H in HIV-2 conferred a greater-than-additive increase in raltegravir resistance. 2011 AIDS (London, England) Result HIV N155H;Q148R 42;31 47;36 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Taken together, these findings indicate that integrase substitutions Q148R and N155H confer moderate levels of raltegravir resistance, and that the combination of these two changes produces more than 1000-fold resistance to the drug in HIV-2. 2011 AIDS (London, England) Result HIV N155H;Q148R 79;69 84;74 IN 45 54 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. The Y143C change alone had no statistically significant effect with regard to raltegravir sensitivity in HIV-2. 2011 AIDS (London, England) Result HIV Y143C 4 9 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Thus, the EC50 for Q148R with N155H HIV-2 was more than 10 mumol/l. 2011 AIDS (London, England) Result HIV N155H;Q148R 30;19 35;24 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. To examine the phenotypic effects of specific changes in HIV-2 integrase, we constructed individual full-length clones of HIV-2 ROD9 encoding the single amino acid replacements Y143C, Q148R and N155H. 2011 AIDS (London, England) Result HIV N155H;Q148R;Y143C 194;184;177 199;189;182 IN 63 72 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. We also constructed a variant of HIV-2 ROD9 encoding the combination of Q148R and N155H on the same viral genome (Q148R with N155H). 2011 AIDS (London, England) Result HIV N155H;N155H;Q148R;Q148R 82;125;72;114 87;130;77;120 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. We initially assessed the replication capacity of Y143C, Q148R, N155H and Q148R with N155H HIV-2 by transfecting full-length plasmids encoding these genotypes into 293T-17 cells. 2011 AIDS (London, England) Result HIV N155H;N155H;Q148R;Q148R;Y143C 64;85;57;74;50 69;90;62;79;55 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Y143C and Q148R also conferred statistically significant declines in replication capacity, with mean titers 4.9-fold and 17-fold lower than that of the parental ROD9 strain, respectively. 2011 AIDS (London, England) Result HIV Q148R;Y143C 10;0 15;5 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Cells expressing any envelope with the T569A change had the lowest amount of cleaved Env, ranging from 22-23 % of the total Env. 2011 Virology Result HIV T569A 39 44 Env;Env;Env 21;85;124 29;88;127 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Cells expressing Env encoding the T569A change, either alone or in combination with a change at 675, had the smallest percentage of cleaved Env. 2011 Virology Result HIV T569A 34 39 Env;Env 17;140 20;143 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. However, cells expressing the Env variant with the change from Thr to Ala at position 569 (Q461e2TA) showed a clear and reproducible shift in fluorescence intensity, indicating that this variant is capable of binding b12 MAb even though it is not sensitive to neutralization by this NAb. 2011 Virology Result HIV T569A 63 89 Env 30 33 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. However, the magnitude of the difference between the T569A and other variants may be as little as ~2-fold or as much as ~5-fold. 2011 Virology Result HIV T569A 53 58 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Importantly, the overall findings are the same with the different antibody probes: the levels of cleaved Env are consistently lower for variants with the T569A mutation. 2011 Virology Result HIV T569A 154 159 Env 105 108 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. In all cases, the IC50 values were similar (within 4-fold) when comparing viruses with these three different amino acid changes at 675, either alone or in combination with the Thr to Ala change at position 569. 2011 Virology Result HIV T569A 176 209 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. In general, viruses encoding the Thr to Ala change at position 569 had the least amount of cleaved Env, whether T569A was alone or in combination with the second change at 675. 2011 Virology Result HIV T569A;T569A 112;33 117;66 Env 99 102 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Similar results were observed with VRC01: the combination of T569A and I675V increased neutralization susceptibility compared to the parental Q461e2 (IC50 0.3 microg/ml and 1.6 microg/ml, respectively); the individual mutants had an intermediate effect (Table 2). 2011 Virology Result HIV I675V;T569A 71;61 76;66 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Similar to previously published results, the combination of a change from Thr to Ala at position 569 and Ile to Val at position 675 introduced into the neutralization-resistant Q461e2 (Q461e2TAIV) resulted in a dramatic increase in neutralization sensitivity to various NAbs, including both MAbs and polyclonal NAbs in plasma pooled from HIV-positive individuals (Table 1). 2011 Virology Result HIV I675V;T569A 105;74 131;100 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Since the first description of the effect of the T569A and I675V amino acid changes on neutralization sensitivity, several potent MAbs have been isolated, notably VRC01 and PG9. 2011 Virology Result HIV I675V;T569A 59;49 64;54 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. The I165V change lies within epitope for 4E10, and thus could impact 4E10 binding. 2011 Virology Result HIV I165V 4 9 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. The MAb PG9 did neutralize Q461e2TAIV with modest potency (IC50 2.6 microg/ml); and there was also some detectable neutralization of the variant bearing the T569A mutation alone (IC50 7.2 microg/ml), but neutralization was not achieved at the highest concentration tested (10 microg/ml) for the variant bearing Env with a change at position 675. 2011 Virology Result HIV T569A 157 162 Env 311 314 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. The T569A change alone had little impact on neutralization sensitivity: neither the pooled plasma nor MAb b12 achieved 50% neutralization of Q461e2TA while the MAbs 4E10 and 2F5 resulted in detectable but modest neutralization (IC50 values of 18.8 and 12.6 microg/ml, respectively). 2011 Virology Result HIV T569A 4 9 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. There was more significant and consistent shift in fluorescence intensity for each of the viruses encoding a change from Ile at position 675, either alone (Q461e2IV, Q461e2IA, Q461e2IT) or in combination with the Thr to Ala change at position 569 (Q461e2TAIV, Q461e2TAIA, Q461e2TAIT), suggesting increased binding compared to the parental Env. 2011 Virology Result HIV T569A 213 246 Env 339 342 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. To examine whether the increase in neutralization sensitivity of the I675V variant to gp41-specific MAbs was due to the loss of an Ile or the presence of a Val at position 675, we investigated the neutralization sensitivity of Q461e2-derived viruses with other uncharged amino acids at this position, either alone or in combination with the T569A change. 2011 Virology Result HIV I675V;T569A 69;341 74;346 gp41 86 90 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Virus with only the Ile to Val change at position 675 (Q461e2IV) showed > 250-fold increase in neutralization sensitivity to the gp41-directed MAbs, 4E10 and 2F5 (IC50 values of 0.1 microg/ml) when compared with Q461e2. 2011 Virology Result HIV I675V 20 53 gp41 129 133 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Viruses with a change from Ile to either an Ala or Thr at position 675 paired with the T569A change (Q461e2TAIA and Q461e2TAIT, respectively), also showed similar neutralization profiles to a variant encoding the Val at 675 (Q461e2TAIV). 2011 Virology Result HIV T569A 87 92 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. 1A), since a P147A mutant was unable to produce virus particles (i.e., RT activity in the supernatant fluid of transfected cells was not detectable). 2011 Virology Result HIV P147A 13 18 RT 71 73 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. All of the mutants except for Y145A had approximately WT levels of CypA. 2011 Virology Result HIV Y145A 30 35 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Apparently, these small differences do not affect the outcome of the TRIMCyp assay, although as seen above, other properties of P147L and S149A are clearly distinguishable from the corresponding properties of the noninfectious mutants in a variety of assays including infectivity (Table 1). 2011 Virology Result HIV P147L;S149A 128;138 133;143 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. As might be expected, the infectivity of the completely noninfectious mutants, i.e., Y145A, I150A, and L151A, could not be rescued by VSV-G pseudotyping (Table 1, column 4). 2011 Virology Result HIV I150A;L151A;Y145A 92;103;85 97;108;90 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. As shown in Table 1, column 2, all of the mutants produced significant amounts of particles and even the lowest producer, L151A, exhibited 50% of WT activity. 2011 Virology Result HIV L151A 122 127 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. By analyzing the core structures in a large number of particles (ranging from ~100 - ~400), we determined that for WT and infectious mutants S146A and T148A, the percentage of conical cores was between 40 and 45% (Table 3). 2011 Virology Result HIV S146A;T148A 141;151 146;156 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Collectively, the results demonstrate a dramatic contrast between the levels of viral DNA detected in cells infected with P147L and S149A and the noninfectious I150A. 2011 Virology Result HIV I150A;P147L;S149A 160;122;132 165;127;137 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Collectively, the VSV-G infectivity data suggest that the phenotypes exhibited by P147L and S149A differ from those of the three noninfectious mutants. 2011 Virology Result HIV P147L;S149A 82;92 87;97 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Conical cores were detected in P147L and S149A virus populations at a frequency approximately half that of the WT. 2011 Virology Result HIV P147L;S149A 31;41 36;46 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. For example, MLV Env was unable to rescue the infectivity of P147L and S149A, despite the high level of infectivity of "WT" HIV-1 env- virions pseudotyped with MLV Env in TZM-bl cells (data not shown). 2011 Virology Result HIV P147L;S149A 61;71 66;76 Env;Env;Env 17;130;164 20;133;167 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. For P147L and S149A, between 3 and 5% of total CA was recovered in the core fractions. 2011 Virology Result HIV P147L;S149A 4;14 9;19 Capsid 47 49 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Here, we purified the CA proteins of WT, P147L, and S149A, as well as the Y145A and I150A CA proteins, which were chosen to represent the class of noninfectious mutants that form only aberrant cores. 2011 Virology Result HIV I150A;P147L;S149A;Y145A 84;41;52;74 89;46;57;79 Capsid;Capsid 22;90 24;92 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. However, the Y145A mutant had ~5-fold less CypA than WT, suggesting that this mutant is even more defective than the other noninfectious mutants. 2011 Virology Result HIV Y145A 13 18 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. If detergent concentrations greater than 0.2% (even as low as 0.3%) were used, only low amounts of CA protein could be detected for all of the mutants with the exception of S146A and T148A, which have a WT phenotype (Table 1). 2011 Virology Result HIV S146A;T148A 173;183 178;188 Capsid 99 101 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. In contrast, infectivity was at background level for Y145A, I150A, and L151A. 2011 Virology Result HIV I150A;L151A;Y145A 60;71;53 65;76;58 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. In our experiments, OMK cells were infected with WT and mutants P147L, S149A, and I150A. 2011 Virology Result HIV I150A;P147L;S149A 82;64;71 87;69;76 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. In some experiments, there was a very small difference between the activity of P147L and S149A compared with the activity of I150A, but in other experiments, no difference was detected. 2011 Virology Result HIV I150A;P147L;S149A 125;79;89 130;84;94 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. In some reactions, subtle differences were observed between the WT and these mutants (e.g., formation of somewhat shorter tubes by P147L and elongated narrow tubes by S149A). 2011 Virology Result HIV P147L;S149A 131;167 136;172 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. In this case, we found that P147L infectivity was partially rescued (~44%), whereas S149A infectivity was rescued almost completely (~80%) (Table 2). 2011 Virology Result HIV P147L;S149A 28;84 33;89 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. It was therefore of interest to determine the efficiencies of viral DNA synthesis in infections with WT or each of the P147L, S149A, and I150A mutants. 2011 Virology Result HIV I150A;P147L;S149A 137;119;126 142;124;131 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Moreover, the data further indicate that differences between the two poorly infectious mutants (i.e., P147L and S149A) and the noninfectious mutants that were observed in other assays (see above) do not affect the assay for CA-TRIMCyp interaction. 2011 Virology Result HIV P147L;S149A 102;112 107;117 Capsid 224 226 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Mutants P147L and S149A showed broad peaks of activity, in contrast to the sharp peak seen for WT. 2011 Virology Result HIV P147L;S149A 8;18 13;23 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Surprisingly, despite the poor infectivity of P147L and S149A bearing HIV-1 Env, when pseudotyped with VSV-G, these mutants displayed essentially WT levels of infectivity (86% and 102%, respectively). 2011 Virology Result HIV P147L;S149A 46;56 51;61 Env 76 79 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Taken together, the EM data demonstrate that while the noninfectious mutants are severely defective with respect to virus assembly both in vivo and in vitro, mutants P147L and S149A exhibit an attenuated assembly phenotype. 2011 Virology Result HIV P147L;S149A 166;176 171;181 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. The data showed that P147L and S149A synthesized ~10-fold less of each viral DNA product compared to WT. 2011 Virology Result HIV P147L;S149A 21;31 26;36 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. The env+ mutants that were infectious, i.e., S146A and T148A, had WT levels of infectivity when env- virions were pseudotyped with VSV-G. 2011 Virology Result HIV S146A;T148A 45;55 50;60 Env;Env 4;96 7;99 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. The P147L and S149A assemblies had structures that were similar to WT. 2011 Virology Result HIV P147L;S149A 4;14 9;19 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. The results for the two mutants were essentially the same, although it appears that S149A made more 2-LTR circles than P147L. 2011 Virology Result HIV P147L;S149A 119;84 124;89 LTR 102 105 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. These results show that mutants P147L and S149A retain minimal amounts of CA and somewhat higher levels of RT in core fractions. 2011 Virology Result HIV P147L;S149A 32;42 37;47 Capsid;RT 74;107 76;109 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. This suggests that at least with respect to this parameter, P147L may be somewhat more defective than S149A. 2011 Virology Result HIV P147L;S149A 60;102 65;107 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. This suggests that the inability to synthesize viral DNA in I150A-infected cells is likely due to the complete absence of normal cores in the virion population. 2011 Virology Result HIV I150A 60 65 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Thus, there appear to be small, but reproducible differences between the core stability of P147L and S149A compared with the core stability of the noninfectious mutants. 2011 Virology Result HIV P147L;S149A 91;101 96;106 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. To demonstrate that rescue of P147L and S149A infectivity by VSV-G can also occur in a different target cell type, the experiment was repeated using the TZM-bl assay for infectivity (Table 2). 2011 Virology Result HIV P147L;S149A 30;40 35;45 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. What is particularly striking, however, is that in contrast to these CA proteins, neither Y145A nor I150A CA formed any recognizable structures. 2011 Virology Result HIV I150A;Y145A 100;90 105;95 Capsid;Capsid 69;106 71;108 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. When infectivity of env+ virus was measured, it was observed that mutants S146A and T148A had significant levels of infectivity, similar to those of the WT, whereas P147L and S149A had only 4-5% of WT infectivity (column 3). 2011 Virology Result HIV P147L;S146A;S149A;T148A 165;74;175;84 170;79;180;89 Env 20 23 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. With I150A, the amount of DNA products synthesized was ~104 lower than WT and the two late products were not detectable. 2011 Virology Result HIV I150A 5 10 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. WT, S146A, and T148A each had between 15 and 20% of total RT in core fractions, whereas the noninfectious mutants had <=1% RT in cores. 2011 Virology Result HIV S146A;T148A 4;15 9;20 RT;RT 58;123 60;125 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. WT, S146A, and T148A had ~40% of total CA associated with the core, whereas Y145A, I150A, and L151A had barely detectable amounts. 2011 Virology Result HIV I150A;L151A;S146A;T148A;Y145A 83;94;4;15;76 88;99;9;20;81 Capsid 39 41 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. Among SSA, RT-M184I/V and PR-M46L were the most frequent mutations, respectively, meanwhile in both Spanish natives and CSA, RT-T215rev and PR-V82A were the most prevalent substitutions. 2011 PloS one Result HIV M184I;M184V;M46L;V82A 14;14;29;143 21;21;33;147 PR;PR;RT;RT 26;140;11;125 28;142;13;127 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. Both specimens harboured mutations F53L and L90M at PR and M41L, K103N, L210W and T215D at RT. 2011 PloS one Result HIV F53L;K103N;L210W;L90M;M41L;T215D 35;65;72;44;59;82 39;70;77;48;63;87 PR;RT 52;91 54;93 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. For NNRTI-resistance, K103N was the most frequent mutation in all groups, although its prevalence was higher in SSA (4.7% [CI: 1.5-7.8]). 2011 PloS one Result HIV K103N 22 27 NNRTI 4 9 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. In fact, K103N was the most prevalent mutation in all periods, and it was the mutation found in a third of the cases (15/45) where a single TDR mutation was found. 2011 PloS one Result HIV K103N 9 14 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. The temporal trend of specific mutation prevalences showed significant reductions from 2000-03 to 2007-10 for tymidine-analogue mutations together (8.8% [CI: 2.1-15.6] to 2.4% [CI: 0.5-4.3], p trend = 0.03) and K103N (10.3% [CI: 3.1-17.5] to 3.2% [CI: 1-5.4], p trend = 0.02) and non-significant reduction for M184I/V (4.4% [CI: -0.5-9.3] to 2.4% [CI: 0.5-4.3], p trend = 0.67). 2011 PloS one Result HIV K103N;M184I;M184V 211;310;310 216;317;317 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. This result was also obtained when comparing patients infected with viruses carrying or not the mutation M184I/V (3.9 log [SD: 0.86] vs. 2011 PloS one Result HIV M184I;M184V 105;105 112;112 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. HIV-1 capsid mutation E45A delays capsid disassembly in HeLa cells. 2011 Structure (London, England Result HIV E45A 22 26 Capsid;Capsid 6;34 12;40 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Microtubules were also observed in half of the E45A HIV-1 tomograms containing GFP signals but no recognizable cone-shaped HIV-1 cores. 2011 Structure (London, England Result HIV E45A 47 51 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. On the other hand, of the fluorescent E45A HIV-1 particles examined (n = 22), 23 % were enveloped, intact virions and 27 % were cytoplasmic, cone-shaped cores. 2011 Structure (London, England Result HIV E45A 38 42 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Quantitative comparison of wild-type and E45A CA mutant HIV-1 infected cells indicates a striking difference between the particles (Figure 4D). 2011 Structure (London, England Result HIV E45A 41 45 Capsid 46 48 HIV infections 56 70 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Since we did not find intact wild-type HIV-1 cores in tomograms containing intracellular GFP signals, we decided to look at a previously characterized mutant with the E45A amino acid substitution in capsid, which presumably yields more stable cores compared to the wild-type. 2011 Structure (London, England Result HIV E45A 167 171 Capsid 199 205 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. The optical behavior of E45A particles was similar to that of wild-type particles to some degree, displaying both stationary and directed movement towards the nucleus. 2011 Structure (London, England Result HIV E45A 24 28 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Using our correlative method, we tracked and analyzed E45A virions in a manner similar to the wild-type capsid virus. 2011 Structure (London, England Result HIV E45A 54 58 Capsid 104 110 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Although interpreting this data should be done based on the understanding that the binding of 5e is suboptimal, the reduced sensitivity to the effects of the Y143R mutation are consistent with the X-ray crystal structure of the homologous prototype foamy virus (PFV) integrase in complex with raltegravir (Figure 2A). 2012 Chemical biology & drug design Result HIV Y143R 158 163 IN 267 276 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. As with the G140S/Q148H mutation, this difference in sensitivity may be related to interactions of raltegravir and 5e with the metal ions at the active site. 2012 Chemical biology & drug design Result HIV G140S;Q148H 12;18 17;23 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Binding of inhibitors to PFV IN bearing the S217H mutation, requires energetically unfavorable movement of the protein backbone to accommodate the His side chain. 2012 Chemical biology & drug design Result HIV S217H 44 49 IN 29 31 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Consistent with the in vitro data for the raltegravir-resistant IN mutants (Table 2), Raltegravir showed a greater than 400 - fold loss of antiviral efficacy against the vector carrying the G140S/Q148H double mutant as compared to the WT (Table 3). 2012 Chemical biology & drug design Result HIV G140S;Q148H 190;196 195;201 IN 64 66 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. For example, while raltegravir was approximately 26-fold less potent against the Y143R mutant than WT, inhibitor 5e showed a smaller loss of potency (2-fold) (Table 2). 2012 Chemical biology & drug design Result HIV Y143R 81 86 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. In contrast, inhibitor 5e displayed only a 2-fold loss of potency against the G140S/Q148H mutant vector, thereby making it approximately 200-fold and 3-fold less susceptible, respectively, to the effects of this double mutant. 2012 Chemical biology & drug design Result HIV G140S;Q148H 78;84 83;89 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. In order to test the susceptibility of the bicyclic hydroxy-1H-pyrrolopyridine-triones to some of the known resistance mutants, in vitro assays were performed against a panel of enzymes that included the wild-type (WT) IN and the three key mutant forms G140S/Q148H, Y143R and N155H (Table 2). 2012 Chemical biology & drug design Result HIV G140S;N155H;Q148H;Y143R 253;276;259;266 258;281;264;271 IN 219 221 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Inhibitor 5e was also approximately 2-fold less sensitive to the effects of the N155H mutation than raltegravir (7-fold loss versus 4-fold loss, respectively) (Table 3). 2012 Chemical biology & drug design Result HIV N155H 80 85 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. It is possible that the G140S/Q148H mutant alters inhibitor - metal binding, and that such alteration is less deleterious for 5e. 2012 Chemical biology & drug design Result HIV G140S;Q148H 24;30 29;35 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Modeling studies on IN have also suggested that introduction of conformational rigidity into an inhibitor may lessen deleterious effects of the G140S/Q148H mutations. 2012 Chemical biology & drug design Result HIV G140S;Q148H 144;150 149;155 IN 20 22 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Similar steric considerations may contribute to a loss of potency by ST inhibitors against the Q148H mutation in HIV-1 IN. 2012 Chemical biology & drug design Result HIV Q148H 95 100 IN 119 121 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Similarly, consistent with the in vitro data shown in Table 3, analogue 5e had loss of potency approximately 20-fold lower than raltegravir against vectors that individually carry the Y143R (approximately 40-fold loss for raltegravir and 2-fold loss for 5e) and 13-fold lower for N155H mutations (38-fold loss for Raltegravir and 3-fold loss for 5e). 2012 Chemical biology & drug design Result HIV N155H;Y143R 280;184 285;189 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. The G140S/Q148H double mutant caused approximately a 100-fold reduction in the potency of raltegravir. 2012 Chemical biology & drug design Result HIV G140S;Q148H 4;10 9;15 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. The histidine imidazole ring of the N224H mutant shifts the catalytic D128 and E221 carboxylates. 2012 Chemical biology & drug design Result HIV N224H 36 41 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. This idea is supported by observations that the resistance to raltegravir imparted by the N155H mutation arises from perturbations related to the divalent metal ions and to direct raltegravir - enzyme contacts. 2012 Chemical biology & drug design Result HIV N155H 90 95 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. To complement the biochemical data, HIV-1 vectors replicating the resistant IN mutants G140S/Q148H, Y143R and N155H were expressed in cultured cells and the cytoprotecive effects of raltegravir (1), MK-0536 (2) and 5e were evaluated (Table 4). 2012 Chemical biology & drug design Result HIV G140S;N155H;Q148H;Y143R 87;110;93;100 92;115;98;105 IN 76 78 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Among the more polymorphic PI mutations (nevertheless included in the IAS-USA December 2010 list as PI-resistance mutations) the most prevalent ones were E35D, M36I, L63P and V91S reaching a percentage ranging between 30% and 50%. 2011 PloS one Result HIV E35D;L63P;M36I;V91S 154;166;160;175 158;170;164;179 PI;PI 27;100 29;102 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Both the LASSO and the LAR/LASSO models only include a maximum of 3 main effects: pre-TCE viral load and mutation V82A (LAR) and pre-TCE viral load and mutations I54V and V82A (LASSO) as well as their interactions with viral load. 2011 PloS one Result HIV I54V;V82A;V82A 162;114;171 166;118;175 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. The ASE was greatly reduced when pre-TCE viral load entered the model and additionally reduced when V82A entered the model. 2011 PloS one Result HIV V82A 100 104 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. The most prevalent of these mutations was V82F, detected in 5-8% of patients respectively in UK CHIC/HDRD and EuroSIDA. 2011 PloS one Result HIV V82F 42 46 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Two 2-way interactions were identified to improve the fit of the models: I62V/A82V (weight of I62V decreased to -0.51 when A82V was not detected) and I15V/A82V (weight of I15V increased to +0.50 when A82V was not detected, likelihood ratio test p = 0.0001). 2011 PloS one Result HIV A82V;A82V;A82V;A82V;I15V;I15V;I62V;I62V 78;123;155;200;150;171;73;94 82;127;159;204;154;175;77;98 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. When we used the best subset selector, LSE estimates of the coefficients and 10-fold CV to identify our model potentially leading to a novel LPV/r score, besides pre-TCE viral load, 5 mutations were selected: I15V (parameter estimate = +0.13), K20I (estimate = -0.26), I54V (estimate = -0.29), I62V (estimate = -0.11) V82A (estimate = -0.60) and V91S (estimate = +0.11). 2011 PloS one Result HIV I15V;I54V;I62V;K20I;V91S 209;269;294;244;346 213;273;298;248;350 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. A trend toward association with M184V (PP[OR<1] = 92%) was also observed. 2011 PloS one Result HIV M184V 32 37 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Among the efavirenz-based group, 93% had virus with one or more NNRTI mutation: K103N was present in 83% (32% as the sole mutation). 2011 PloS one Result HIV K103N 80 85 NNRTI 64 69 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Conversely, lower viral load at genotyping was associated with occurrence of mutation M184V (OR = 0.48, 90%-CI = [0. 2011 PloS one Result HIV M184V 86 91 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Conversely, the use of an efavirenz-based regimen was associated with significantly increased risks of the mutations P225H (PP[OR>1]>99%), V106M (PP[OR>1]>99%), K103N (PP[OR>1]>99%), L100I (PP[OR>1] = 97%), T215Y (PP[OR>1] = 97.5%) and L210W (PP[OR>1]>99%). 2011 PloS one Result HIV K103N;L100I;L210W;P225H;T215Y;V106M 161;183;236;117;207;139 166;188;241;122;212;144 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. In the NVP-based treatment group, 100% had virus with one or more NNRTI mutations: Y181C/I was present in 56% (18% as the sole mutation), G190A/S in 30% (4%) and K103N in 28% (18%). 2011 PloS one Result HIV G190A;G190S;K103N;Y181C;Y181I 138;138;162;83;83 145;145;167;90;90 NNRTI 66 71 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Longer duration of failure was also significantly associated with higher risk of M184V (PP[OR>1] = 94%) and NNRTI mutations G190A (PP[OR>1] = 95%), K101E (PP[OR>1] = 94%) and A98G (PP[OR>1] = 99%). 2011 PloS one Result HIV A98G;G190A;K101E;M184V 175;124;148;81 179;129;153;86 NNRTI 108 113 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Longer duration of virologic failure was found significantly associated with higher risk of all TAM-2 mutations (D67N, K70R, K219Q/E, T215F) and the T215Y mutation with ORs ranging from 1.25 to 1.84 and PP[OR>1]>98% (Figure 2D). 2011 PloS one Result HIV D67N;K219E;K219Q;K70R;T215F;T215Y 113;125;125;119;134;149 117;132;132;123;139;154 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. More specifically, TDF, when compared with d4T, was found strongly associated with greater risk of mutations Y115F and K65R (PP[OR>1]>99%), and, with less clear evidence (PP[OR>1]>92) with greater risk of mutations Y181I, V179F, and A62V (Figure 2B). 2011 PloS one Result HIV A62V;K65R;V179F;Y115F;Y181I 233;119;222;109;215 237;123;227;114;220 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Occurrence of K103N was associated with shorter duration of failure (PP[OR<1] = 97%). 2011 PloS one Result HIV K103N 14 19 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Of the nine K65R mutations observed, all were found in patients on NVP-based treatment, 6 among patients on TDF and 3 among those on d4T. 2011 PloS one Result HIV K65R 12 16 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. One fourth of samples had Y181C/I or G190A mutations. 2011 PloS one Result HIV G190A;Y181C;Y181I 37;26;26 42;33;33 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. TDF was also associated with lower risk of mutation M184V (PP[OR<1] = 99%) and with less significance, of mutation V75I (PP[OR<1] = 89%). 2011 PloS one Result HIV M184V;V75I 52;115 57;119 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. The cluster D67N-K70R-K219Q-M184V, the first three of which are in the TAM-2 pathway, contained the NRTI mutations most likely to occur together in both treatment groups (Figure 3B). 2011 PloS one Result HIV D67N;K219Q;K70R;M184V 12;22;17;28 16;27;21;33 NRTI 100 104 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. The K103N (P<0.001) and P225H (P<0.001) mutations were each significantly more common and Y181C/I (P = 0.001), G190A (P = 0.002) and K101Q/E (P = 0.003) were each significantly less common among subjects failing efavirenz-based treatment as compared to those failing nevirapine-based treatment. 2011 PloS one Result HIV G190A;K101E;K101Q;K103N;P225H;Y181C;Y181I 111;133;133;4;24;90;90 116;140;140;9;29;97;97 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. The most prevalent NRTI mutations in both NNRTI groups were M184V/I (93% in nevirapine and 66% in efavirenz). 2011 PloS one Result HIV M184I;M184V 60;60 67;67 NNRTI;NRTI 42;19 47;23 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. When adjusted for the effects of failure duration, viral load and NRTI backbone, the analysis, presented in Figure 2A, showed that the use of a nevirapine-based regimen was associated with significantly increased risks of mutations G190A (the posterior probability of G190A occurring on a nevirapine-based regimen or PP[OR<1] was >99%), Y188L (PP[OR<1] = 97.5%), Y181C (PP[OR<1]>99%), K101E (PP[OR<1]>99%), Y115F (PP[OR<1]>99%) and K65R PP[OR<1]>99%) as compared with an efavirenz-based treatment. 2011 PloS one Result HIV G190A;G190A;K101E;K65R;Y115F;Y181C;Y188L 232;268;385;432;407;363;337 237;273;390;436;412;368;342 NRTI 66 70 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. With NVP, the next two mutations, K219E and T215F, complete the TAM-2 cluster, whereas with EFV, the three TAM-1 mutations (M41L, L210W, and T215Y) appear next, along with the K219E from the TAM-2 pathway. 2011 PloS one Result HIV K219E;K219E;L210W;M41L;T215F;T215Y 34;176;130;124;44;141 39;181;135;128;49;146 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. 5A), though sera from Q105N_QuilA animals bound slightly better relative to sera from the 3 other groups, suggesting the somewhat greater presence of antibodies with epitopes overlapping the gp120 outer domain in this group of immunized animals. 2012 Vaccine Result HIV Q105N 22 27 gp120 191 196 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. 5B), indicating that a comparatively larger fraction of CD4bs-specific antibodies had been elicited by specifically combining mutant Q105N with Quil A. 2012 Vaccine Result HIV Q105N 133 138 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. 6), suggesting that the Q105N-immunized animals contain a greater abundance of antibodies to epitopes overlapping the epitopes of those two mAbs. 2012 Vaccine Result HIV Q105N 24 29 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Anti-Q105N MPL sera also bound its homologous antigen (DeltaN2mCHO(Q105N)) preferentially, suggesting the possible creation of neo-epitopes when Q105N is mixed with MPL. 2012 Vaccine Result HIV Q105N;Q105N;Q105N 5;67;145 10;72;150 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. CD4-IgG2, which used here as a surrogate for CD4, bound poorly to Q105N relative to gp120wt and mAbs F105 and VRC03 did not bind Q105N at all. 2012 Vaccine Result HIV Q105N;Q105N 66;129 71;134 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Given the antigenicity of Q105N, we wished to assess the impact of adjuvant formulation on the magnitude of antibody responses. 2012 Vaccine Result HIV Q105N 26 31 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Having determined that some level of CD4bs-directed responses was elicited with Q105N formulated with Quil A, we assessed the neutralizing activity of sera from all 4 immunization groups by testing them on tier 1B and 2 subtype B viruses, SS1196 and JR-FL, and the tier 1B subtype C virus ZM197M. 2012 Vaccine Result HIV Q105N 80 85 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. However, this preference was less pronounced with Q105N_QuilA sera. 2012 Vaccine Result HIV Q105N 50 55 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. However, unlike the DeltaN2mCHO-GDMR mutant, Q105N does not eliminate binding of all non-neutralizing CD4bs mAbs. 2012 Vaccine Result HIV Q105N 45 50 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Hyperglycosylated mutant Q105N limits access of select CD4bs antibodies. 2012 Vaccine Result HIV Q105N 25 30 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Most notably, Q105N_QuilA sera bound significantly better to RSC3 than sera from the other 3 serum groups. 2012 Vaccine Result HIV Q105N 14 19 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Q105N in Quil A adjuvant elicits higher levels of CD4bs-specific antibodies. 2012 Vaccine Result HIV Q105N 0 5 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Sera from all 4 animal groups inhibited b12 binding to roughly the same extent, with the level of inhibition by the Q105N_MPL sera somewhat greater than the other 3 sera. 2012 Vaccine Result HIV Q105N 116 121 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Sera from both the Q105N_MPL and Q105N_QuilA animals inhibited the binding of mAbs b13 and VRC03 to a greater extent (30-40%) than sera from the gp120wt groups (10-20%). 2012 Vaccine Result HIV Q105N;Q105N 19;33 24;38 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Serum antibodies elicited by immunization with Q105N do not show neutralizing activity. 2012 Vaccine Result HIV Q105N 47 52 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Serum antibodies elicited by Q105N bind epitopes that partially overlap the CD4bs on gp120. 2012 Vaccine Result HIV Q105N 29 34 gp120 85 90 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. 2012 Vaccine Result HIV Q105N 65 70 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. The resulting mutant, DeltaN2mCHO(Q105N), has a total of 11 extra glycans on gp120 relative to the wild-type sequence. 2012 Vaccine Result HIV Q105N 34 39 gp120 77 82 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. The V3-specific antibody B4e8 did not bind to Q105N as expected given its inability to bind the parental mutant DeltaN2mCHO. 2012 Vaccine Result HIV Q105N 46 51 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. These results suggest that despite the presence of a fraction of CD4bs-like antibodies in Q105N_QuilA sera, the elicited antibodies may not be sufficiently abundant to neutralize virus effectively. 2012 Vaccine Result HIV Q105N 90 95 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. To assess CD4bs exposure on mutant Q105N, the binding of a panel of mAbs was evaluated relative to wild-type JR-FL gp120. 2012 Vaccine Result HIV Q105N 35 40 gp120 115 120 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. We found that both gp120wt and Q105N formulated with Quil A elicited higher titres on average than when formulated with MPL. 2012 Vaccine Result HIV Q105N 31 36 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. All chemical crosslinks involving the ASV I146C derivative are maintained with the bases of the corresponding nucleotides. 2011 PloS one Result HIV I146C 42 47 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Although the orientation of the 3'- end nucleotide is slightly different in PFV IN, the presence of the flexible linkers carrying thiol groups is likely to have allowed successful crosslinking of both modified nucleotides to ASV IN D64C and E157C derivatives. 2011 PloS one Result HIV D64C;E157C 232;241 236;246 IN;IN 80;229 82;231 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Because the W259A substitution has been shown to impair dimer formation, this result was anticipated. 2011 PloS one Result HIV W259A 12 17 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Consequently, to establish covalent links to the end of the DNA substrate near the IN active site, we replaced Ile146 with cysteine ( Table 1 ). 2011 PloS one Result HIV I146C 111 131 IN 83 85 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Contact between I146C and nucleotide 2 of the non-cleaved strand of viral DNA was also detected by chemical crosslinking ( Tables 2 , 3 ). 2011 PloS one Result HIV I146C 16 21 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Crosslinking of the C23S/C125S/E157C/F199K/W259A IN derivative with both modified DNA substrates using the pH activation method produced slightly lower yields than crosslinking of the C23S/C125S/E157C/F199K IN derivative (Compare Figure 9A and 9B pH-P-SS lanes), and no adduct band was observed above the position of dimeric IN in Figure 9B . 2011 PloS one Result HIV C125S;C125S;C23S;C23S;E157C;E157C;F199K;F199K;W259A 25;189;20;184;31;195;37;201;43 30;194;24;188;36;200;42;206;48 IN;IN;IN 49;207;327 51;209;329 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. For example, results with the I146C derivative of ASV IN implicate this residue in interactions with nucleotide 3 of the cleaved strand and nucleotide 2 of the non-cleaved strand of viral DNA. 2011 PloS one Result HIV I146C 30 35 IN 54 56 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. For experiments performed with the full length E157C IN, the highest yields were observed with the 3'-attached 3-mercaptopropanol phosphodiester modified substrates (P-SS), similar for both pH and DTNB activation. 2011 PloS one Result HIV E157C 47 52 IN 53 55 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. In some constructs the Cys125 was substituted with serine, and a W259A substitution was included. 2011 PloS one Result HIV C125S;W259A 23;65 57;70 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. It is therefore quite plausible that the D64C derivative could likewise coordinate Mg2+ with Asp121 in site I alone (or perhaps with Glu157 in site II) in the presence of additional contacts with DNA. 2011 PloS one Result HIV D64C 41 45 Asp 93 96 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Our photocrosslinking data indicate that S124C of ASV IN makes contact with the third nucleotide of the cleaved strand of target DNA, and a minor contact with nucleotide 8 of the same strand ( Figure 10B ). 2011 PloS one Result HIV S124C 41 46 IN 54 56 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Photo- and chemical crosslinking data for I146C of ASV IN identified nucleotide 3 of the cleaved strand of viral DNA as the point of contact. 2011 PloS one Result HIV I146C 42 47 IN 55 57 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Q148C was also reported to chemically crosslink to thiol-modified 5'-end of viral DNA. 2011 PloS one Result HIV Q148C 0 5 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. reported the formation of S-S bond between Y143C and position 2 next to 5'-end of the non-processed viral DNA. 2011 PloS one Result HIV Y143C;Y143C 44;43 49;48 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. The C23S/C125S/E157C/F199K IN derivative ( Figure 9A ) produced higher yields of crosslinking than the single E157C IN derivative (not shown) with both modified DNA substrates, regardless of the activation method (pH-dependent or DTNB). 2011 PloS one Result HIV C125S;C23S;E157C;F199K;E157C 9;4;15;21;110 14;8;20;26;115 IN;IN 27;116 29;118 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. The choice to substitute Cys for Ile146, located in the flexible loop near the active site of ASV IN, was based on the results from a number of previous studies. 2011 PloS one Result HIV I146C 25 39 IN 98 100 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. The fact that the E157C IN construct is capable of binding a metal cation suggests that the ion binds in site I (Asp64-Asp121), as seen in previous structures of IN with a disordered region encompassing the Glu157 residue. 2011 PloS one Result HIV E157C 18 23 Asp;Asp;IN;IN 113;119;24;162 116;122;26;164 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. The most efficient crosslinking to E157C and D64C was observed in the presence of 10 mM MgCl2, indicating that, in contrast to other IN-DNA contact sites, crosslinking to these derivatives required the presence of Mg2+ (data not shown). 2011 PloS one Result HIV D64C;E157C 45;35 49;40 IN 133 135 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. The W259A replacement has been shown to block formation of ASV IN dimers. 2011 PloS one Result HIV W259A 4 9 IN 63 65 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. We also showed in previous experiments with a D64N derivative that Asp121 alone can bind a single Zn2+ cation in site I. 2011 PloS one Result HIV D64N 46 50 Asp 67 70 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. After modeling the positions of A114S. 2012 Virology Result HIV A114S 32 37 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. As shown In Table 2, the A114C mutant demonstrated a 2.5 - 4.8 fold higher Kd than WT RT, with little difference in the kpol values. 2012 Virology Result HIV A114C 25 30 RT 86 88 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. First, as shown in Table 1, the Km values of A114S, A114C and A114V RTs with normal dTTP incorporation continue to incrementally increase by 18, 25 and 278-folds, compared to the Km value of wild type RT, which is consistent with the previous observation. 2012 Virology Result HIV A114C;A114S;A114V 52;45;62 57;50;67 RT;RT 68;201 71;203 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. First, the active site concentrations of WT and A114C RT protein were determined with an excess of T/P using a rapid quench technology. 2012 Virology Result HIV A114C 48 53 RT 54 56 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Further indicating the impaired transduction capability of the A114S vector was due to the limited cellular dNTP pools in serum starved cells. 2012 Virology Result HIV A114S 63 68 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. However, the A114S vector showed significantly reduced transduction in serum starved HLFs. 2012 Virology Result HIV A114S 13 18 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. However, the A114S. 2012 Virology Result HIV A114S 13 18 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. However, when the same analysis was conducted with acyTTP incorporation, A114S, A114C and A114V RT displayed only 10, 3 and 10-fold increase in Km, when compared to wild type. 2012 Virology Result HIV A114C;A114S;A114V 80;73;90 85;78;95 RT 96 98 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. In addition, this further suggests that the absence of the 2' and 3' carbons space in acyTTP, complements the large side chain volumes of the A114C and A114V mutant RTs, supporting the idea that the side chain of HIV-1 RT residue 114 lies proximal to the 2' and 3' carbons of the incoming dNTP substrate. 2012 Virology Result HIV A114C;A114V 142;152 147;157 RT;RT 165;219 168;221 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Indeed, the reduced space for the sugar moiety of a dNTP appears to be inevitable after calculating the distance of A114S to the 3'OH, 1.96A. 2012 Virology Result HIV A114S 116 121 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Indeed, the reduced transduction of the A114S vector could be rescued by 1mM dN treatment in serum starved HLFs. 2012 Virology Result HIV A114S 40 45 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Lastly, when the residue 114 was mutated to an even larger side chain, A114I, RT failed to display any detectable primer extension even at 250muM. 2012 Virology Result HIV A114I 71 76 RT 78 80 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Moreover, as shown in Table 2 and Figure 4C, both the kpol and Kd of A114C compared to WT were not affected when acyTTP, a dNTP analog that lacks 2' and 3' carbons of sugar ring, was used as a substrate. 2012 Virology Result HIV A114C 69 74 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Pre-steady-state kinetic analysis for the dNTP binding affinity of WT and A114C mutant HIV-1 RT proteins. 2012 Virology Result HIV A114C 74 79 RT 93 95 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The A114S vector displayed WT levels of transduction in dividing HLFs (grown in 10% serum. 2012 Virology Result HIV A114S 4 9 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The A114V failed to transduce HFLs grown in serum-starved media and demonstrated almost undetectable transduction levels in HLFs grown in serum or serum-starved media supplemented with dNs. 2012 Virology Result HIV A114V 4 9 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The activity of A114V was greatly reduced even at a 2.5muM dNTP concentration. 2012 Virology Result HIV A114V 16 21 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The experimentally determined kobs values were plotted to calculate the Kd and kpol values of WT and A114C proteins with all four dNTPs, as described in the materials and methods section. 2012 Virology Result HIV A114C 101 106 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. These results were expected due to the large addition at 114 of the beta branched side chain of valine, compared to the relatively minimal alterations of an OH or SH group addition with the mutations A114S or A114C. 2012 Virology Result HIV A114C;A114S 209;200 214;205 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. This again indicates a larger dNTP-binding defect generated with this mutation when compared to WT or A114S. 2012 Virology Result HIV A114S 102 107 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. This can be compared to A114V, which still exhibited a detectable activity at high dNTP concentrations. 2012 Virology Result HIV A114V 24 29 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. This experiment is done to ascertain the concentration of active protein present in the WT and A114C RT preparations. 2012 Virology Result HIV A114C 95 100 RT 101 103 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. This suggests that the transduction of a HIV-1 vector carrying the A114S mutation is specifically affected in cells containing low dNTP concentration, but not in dividing HLFs with high cellular dNTP concentrations. 2012 Virology Result HIV A114S 67 72 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. To test our hypothesis, we constructed and purified a series of HIV-1 NL4-3 RT A114 mutant proteins with increasingly longer side chains: A114S, A114C, A114V and A114I. 2012 Virology Result HIV A114C;A114I;A114S;A114V 145;162;138;152 150;167;143;157 RT 76 78 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. To test this we performed a pre-steady-state kinetic analysis and measured the dNTP binding affinity (Kd) and conformational change/catalysis (kpol) of WT RT and the mutant A114C that displayed a milder defect in steady-state kinetics. 2012 Virology Result HIV A114C 173 178 RT 155 157 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Unlike A114S and WT, the A114C vector displayed reduced transduction in HLFs grown in serum. 2012 Virology Result HIV A114C;A114S 25;7 30;12 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. We found that both WT and A114C RT have equal primer template extension at low concentrations of acyTTP; however, A114C RT displayed reduced extension at low dTTP concentrations when compared to WT (Figure 3B). 2012 Virology Result HIV A114C;A114C 26;114 31;119 RT;RT 32;120 34;122 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. We introduced the A114S, A114C or A114V mutation into the pol gene of a HIV-1 vector. 2012 Virology Result HIV A114C;A114S;A114V 25;18;34 30;23;39 Pol 58 61 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. As expected, the CypA insensitive mutants G89V or P90A did not respond significantly to Cs treatment or CypA depletion by RNAi respectively (Figure 6A, B). 2011 PLoS pathogens Result HIV G89V;P90A 42;50 46;54 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. As for N57A, it seems contradictory that HIV-1 CA mutants that are less sensitive to Nup358 depletion are restricted by TRIMNup358. 2011 PLoS pathogens Result HIV N57A 7 11 Capsid 47 49 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. As, N57A is less sensitive to both Nup358 and TRN-SR2 depletion (Figure 3A), we hypothesize that its infectivity defect is caused by an inability to engage these proteins. 2011 PLoS pathogens Result HIV N57A 4 8 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Because G89V and P90A influence targeting in the same direction, we infer that disruption of normal CypA interactions, and possibly Nup358 interactions, result in increased frequency of integration in regions with high densities of transcription units. 2011 PLoS pathogens Result HIV G89V;P90A 8;17 12;21 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Finally, we studied the HIV-1 CA mutant N74D, which is reported to be less sensitive to Nup358 or TRN-SR2 depletion (Figure 3A). 2011 PLoS pathogens Result HIV N74D 40 44 Capsid 30 32 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. For wild type HIV-1 this density was 15 transcription units/MB, whereas for CA mutants N57A or N74D the density was reduced to what is expected for random integration (7-9 transcription units/MB) (Figure 4A and Figure S7). 2011 PLoS pathogens Result HIV N57A;N74D 87;95 91;99 Capsid 76 78 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Hierarchical clustering of the CA mutants based on these data separated the viruses into two groups: N57A and N74D, and the Cyp-binding mutants G89V, P90A and chimeric HIV-1(SIVCA) (Figure 4B). 2011 PLoS pathogens Result HIV G89V;N57A;N74D;P90A 144;101;110;150 148;105;114;154 Capsid 31 33 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. HIV-1 CA mutants N57A and N74D integrated into regions of chromatin associated with a significantly lower density of transcription units and associated features. 2011 PLoS pathogens Result HIV N57A;N74D 17;26 21;30 Capsid 6 8 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. However, the Cyp non-binding mutant HIV-1 CA G89V as well as mutants N74D and N57A, which are less dependent on Nup358/TRN-SR2 were only moderately affected (~3-fold). 2011 PLoS pathogens Result HIV G89V;N57A;N74D 45;78;69 49;82;73 Capsid 42 44 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Importantly, N57A's insensitivity to Nup358 depletion suggests that it does not engage Nup358 during nuclear entry. 2011 PLoS pathogens Result HIV N57A 13 17 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. In addition, it is possible that the decreased binding of N57A as well as N74D to TRIMNup358 is disguised by an increased sensitivity to restriction by this TRIM5 chimera. 2011 PLoS pathogens Result HIV N57A;N74D 58;74 62;78 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. In contrast, the two Cyp-binding mutants, G89V and P90A, exhibited an opposite phenotype, with favored integration into regions of increased density of transcription units (~20 transcription units/MB). 2011 PLoS pathogens Result HIV G89V;P90A 42;51 46;55 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. In fact, Cs treatment retargeted viral integration preferences in a way that phenocopied the CA G89V/P90A substitutions shifting integration preferences into regions of higher gene density (Figure 5A, B). 2011 PLoS pathogens Result HIV G89V;P90A 96;101 100;105 Capsid 93 95 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Indeed, ITC demonstrates that N57A is impaired in binding Nup358Cyp (Kd 55 microM) but not CypA (Kd 7 microM) (Figure 3B). 2011 PLoS pathogens Result HIV N57A 30 34 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Like N57A, N74D bound monomeric Nup358Cyp in ITC experiments with significantly lower affinity than wild type (Kd 95 microM) (Figure 3B) and like N57A, N74D was also restricted by TRIMNup358 (Figure S5A). 2011 PLoS pathogens Result HIV N57A;N57A;N74D;N74D 5;146;11;152 9;150;15;156 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. On the other hand N57A is slightly increased in its sensitivity to aphidicolin particularly after Nup358 depletion. 2011 PLoS pathogens Result HIV N57A 18 22 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Reduction of Nup358 by RNAi led to integration into low gene density/activity regions but preventing CypA binding by CA amino acid substitutions (G89V/P90A) or Cs treatment shifted virus integration preferences into high gene density/activity regions. 2011 PLoS pathogens Result HIV G89V;P90A 146;151 150;155 Capsid 117 119 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. The HIV-1 CA mutant N57A is more severely defective in arrested cells than dividing cells (Figure 3A), suggesting that this residue may have a role in nuclear entry. 2011 PLoS pathogens Result HIV N57A 20 24 Capsid 10 12 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. The infectivity of the HIV-1 CA mutant N74D was slightly reduced by Cs consistent with its reduced sensitivity to Nup358 depletion and supporting the notion that it is still able to recruit CypA as confirmed by ITC (Figure 3B, 6A and Figure S8). 2011 PLoS pathogens Result HIV N74D 39 43 Capsid 29 31 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. The N74D and N57A substitutions are less sensitive to depletion of both Nup358 and TRN-SR2, and N74D gains sensitivity to depletion of other nuclear pore proteins. 2011 PLoS pathogens Result HIV N57A;N74D;N74D 13;4;96 17;8;100 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. The observation that HIV-1 CA mutants P90A and G89V, as well as chimeric HIV-1(SIVCA) integrate into genome regions with higher densities of transcription units and associated features raised the possibility that integration targeting might be influenced by CypA binding to CA. 2011 PLoS pathogens Result HIV G89V;P90A 47;38 51;42 Capsid;Capsid 27;274 29;276 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. These data demonstrate that HIV-1 CA mutants P90A and N74D do not support optimal replication. 2011 PLoS pathogens Result HIV N74D;P90A 54;45 58;49 Capsid 34 36 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. This suggests that G89V, P90A and N74D use Nup358/TRN-SR2 independent routes into the nucleus even in the absence of cell division. 2011 PLoS pathogens Result HIV G89V;N74D;P90A 19;34;25 23;38;29 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. To test whether these CA substitutions affect HIV-1 replication we compared replication of wild type HIV-1 NL4.3 (Ba-L Env) with CA mutants P90A and N74D in spreading infection in HeLa TZM-bl cells. 2011 PLoS pathogens Result HIV N74D;P90A 149;140 153;144 Env;Capsid;Capsid 119;22;129 122;24;131 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. We also found that HIV-1 NL4.3 (Ba-L Env) bearing CA alterations N74D or P90A replicated poorly in primary human MDM from four independent donors, whereas wild type virus replicated efficiently (Figure 4F and Figure S7B). 2011 PLoS pathogens Result HIV N74D;P90A 65;73 69;77 Env;Capsid 37;50 40;52 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. We found that N57A was still restricted by TRIMNup358 (Figure S5), suggesting that increased avidity through Nup358Cyp dimerization in the context of TRIMNup358 may overcome the reduced affinity to monomeric Nup358Cyp. 2011 PLoS pathogens Result HIV N57A 14 18 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. We found that only N57A and MLV infectivities were inhibited by aphidicolin treatment (Figure 3A and Table S1) whereas mutants G89V, P90A and N74D were not affected. 2011 PLoS pathogens Result HIV G89V;N57A;N74D;P90A 127;19;142;133 131;23;146;137 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. We found that the cyclophilin-binding mutants G89V and P90A were insensitive to Nup358 depletion but remained sensitive to TRN-SR2 depletion (Figure 3A). 2011 PLoS pathogens Result HIV G89V;P90A 46;55 50;59 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. We propose that Nup358 and TRN-SR2 define an import pathway used by wild type HIV-1 and that CA amino acid substitutions direct the virus to use Nup358 independent (G89V, or P90A), or Nup358/TRN-SR2 independent (N74D, or N57A) import pathways. 2011 PLoS pathogens Result HIV G89V;N57A;N74D;P90A 165;221;212;174 169;225;216;178 Capsid 93 95 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. We were surprised that HIV-1 CA mutants P90A and N74D, which are less sensitive to depletion of TRN-SR2 and/or Nup358 (Figure 3A), and have different integration site preferences in unmodified cells (Figure 4), were as infectious as wild type virus in single round assays. 2011 PLoS pathogens Result HIV N74D;P90A 49;40 53;44 Capsid 29 31 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Again, mutant Y194E was more severely affected (Figure 3A upper panel and 3B upper panel). 2011 Retrovirology Result HIV Y194E 14 19 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Alongside these residues, we also included in our assays two previously characterized IN mutants W131A and Q168L that were deficient for LEDGF/p75 binding. 2011 Retrovirology Result HIV Q168L;W131A 107;97 112;102 IN 86 88 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. As previously reported, both IN W131A and IN Q168L displayed a weak interaction with LEDGF/p75 (9.3 and 16.3% of IN WT interaction in our assay, respectively). 2011 Retrovirology Result HIV Q168L;W131A 45;32 50;37 IN;IN;IN 29;42;113 31;44;115 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Because IN mutants W131A and Q168L are impaired for interaction with both TNPO3 and LEDGF/p75, we decided to assess more precisely the impact of these mutations on nuclear import in the absence of LEDGF/p75. 2011 Retrovirology Result HIV Q168L;W131A 29;19 34;24 IN 8 10 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Both IN mutants K188Q and Y194A interacted with TNPO3 as well as IN WT, while the substitution of Y194 to Phe or Glu resulted in a 14.4 and 23.5% decrease of TNPO3 binding. 2011 Retrovirology Result HIV K188Q;Y194A 16;26 21;31 IN;IN 5;65 7;67 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. In sharp contrast, K188Q, Y194F and Y194E were almost incapable of concerted integration activities (Figure 3C). 2011 Retrovirology Result HIV K188Q;Y194E;Y194F 19;36;26 24;41;31 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. In sharp contrast, mutation Q168L disrupting the Q168-W132 H-bond results in a major shift to a low molecular weight peak corresponding exclusively to monomers. 2011 Retrovirology Result HIV Q168L 28 33 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. IN W131A behaved mostly as a mixture of tetramers and dimers. 2011 Retrovirology Result HIV W131A 3 8 IN 0 2 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. IN W131A displayed a strong activity at 5 pmoles. 2011 Retrovirology Result HIV W131A 3 8 IN 0 2 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Remarkably, mutation Y194E led to a pronounced shift to monomeric forms. 2011 Retrovirology Result HIV Y194E 21 26 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Substitution of Lys188 for a Gln also resulted to a 64.9% decrease of the binding to LEDGF/p75. 2011 Retrovirology Result HIV Q188K 16 32 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Surprisingly, despite its monomeric elution profile in SEC (Figure 2), Q168L retained a significant catalytic activity. 2011 Retrovirology Result HIV Q168L 71 76 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Surprisingly, the strongest decrease for TNPO3 binding was observed for both LEDGF/p75 interaction-defective integrase IN W131A and IN Q168L (49% and 45% of IN WT, respectively) (Figure 4B). 2011 Retrovirology Result HIV Q168L;W131A 135;122 140;127 IN;IN;IN;IN 109;119;132;157 118;121;134;159 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. The mutations Q168L, K188Q and Y194F partially decreased strand transfer activity. 2011 Retrovirology Result HIV K188Q;Q168L;Y194F 21;14;31 26;19;36 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. The W131A mutant also displayed wild type level of strand transfer activity. 2011 Retrovirology Result HIV W131A 4 9 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. The W131A, Q168L, K188Q and Y194F IN mutants retained near wild type 3' processing activity, while the Y194E mutant was impaired (Figure 3A lower panel and 3B lower panel). 2011 Retrovirology Result HIV K188Q;Q168L;W131A;Y194E;Y194F 18;11;4;103;28 23;16;9;108;33 IN 34 36 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Together, these data suggest that IN mutations reducing TNPO3 binding have a rather limited effect (W131A) or no effect (Q168L) on nuclear import of the PIC. 2011 Retrovirology Result HIV Q168L;W131A 121;100 126;105 IN 34 36 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. While IN Y194F interacted with LEDGF/p75 at wild type level, the substitution of Tyr for a negatively charged Glu or a neutral Ala moderately diminished IN binding to LEDGF/p75 by 26 and 27% respectively (Figure 4A). 2011 Retrovirology Result HIV Y194F 9 14 IN;IN 6;153 8;155 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. 19.5% of the patients presented L74V/I mutation that occur in patients with virologic failure while receiving non-TAM regimens and causes intermediate resistance to DDI and ABC, and a slight increase in susceptibility to AZT and TDF. 2011 Romanian biotechnological letters Result HIV L74I;L74V 32;32 38;38 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. Additional PI-selected accessory mutations were found only in the severe immunosuppressed group and include the highly polymorphic mutations I13V (23.8%), D60E (14.3%) and K55R, an uncommon non-polymorphic mutation. 2011 Romanian biotechnological letters Result HIV D60E;I13V;K55R 155;141;172 159;145;176 PI 11 13 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. Five out of the 21 patients with severe immunosuppression harbored major PI mutations V82A, I54V, and G48V associated with phenotypic resistance to ritonavir. 2011 Romanian biotechnological letters Result HIV G48V;I54V;V82A 102;92;86 106;96;90 PI 73 75 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. Interestingly, six out of the 11 patients with the K103N mutation had not been treated with NNRTIs. 2011 Romanian biotechnological letters Result HIV K103N 51 56 NNRTI 92 98 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. None of the patients presented K219N/R, the mutation that usually occurs in heavily NRTI treated patients, nor multi-nucleoside resistance, via the Q151 or the 68-69 pathway. 2011 Romanian biotechnological letters Result HIV K219N;K219R 31;31 38;38 NRTI 84 88 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. The major NNRTI resistance mutation, K103N, which causes high-level resistance to nevirapine and variable resistance to efavirenz, occurred in 28.9% of all studied patients. 2011 Romanian biotechnological letters Result HIV K103N 37 42 NNRTI 10 15 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. The major NRTI resistance mutation M184V was the most commonly detected (in 52.3% of the severe immunocompromissed patients versus 36.4% and 33.4% of patients with moderate or absent immunosuppression). 2011 Romanian biotechnological letters Result HIV M184V 35 40 NRTI 10 14 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. The most commonly encountered polymorphisms that may induce early development of drug resistance, were L63T, present in 80.5% of the cases and M36I in 77.8% of the cases, followed by L89M (50%), K20R (72.3%) and L10V (63.9%) of the patients. 2011 Romanian biotechnological letters Result HIV K20R;L10V;L63T;L89M;M36I 195;212;103;183;143 199;216;107;187;147 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. Thymidine analog mutations, TAMs, selected by zidovudine (AZT) and stavudine (D4T) were usually accompanying this mutation; TAM-2 pathway (mutations D67N, K70R, T215F) was most commonly encountered in immunossupressed patients (28.6%), as well as other substitutions that by themselves, or while accompanying other mutations, confer NRTI resistance: K219E/K/Q (38.1%) and T69N (19%). 2011 Romanian biotechnological letters Result HIV D67N;K219E;K219K;K219Q;K70R;T215F;T69N 149;350;350;350;155;161;372 153;359;359;359;159;166;376 NRTI 333 337 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Additionally, possibly structural changes in the C-terminal region caused by substitution of Arg-80 by Ala were investigated by nuclear magnetic resonance (NMR) spectroscopy. 2011 BMC structural biology Result HIV R80A 93 106 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. As Arg-80 has previously been reported to be necessary for maintaining binding between Vpr and CypA, SPR experiments were performed on the mutant peptides Vpr75-90 R80A, Vpr75-90 (R76Q, V83I, T84I) and Vpr75-90 (R76Q, V83I, R80A, T84I). 2011 BMC structural biology Result HIV R76Q;R76Q;R80A;T84I;T84I;V83I;V83I 180;212;224;192;230;186;218 184;216;228;196;234;190;222 Vpr;Vpr;Vpr;Vpr 87;155;170;202 90;158;173;205 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. CSI showed that the weak secondary structure of the binding region of Vpr is consistent with that previously reported by others in the literature and is relatively uninfluenced by the R80A mutation (Figure 3). 2011 BMC structural biology Result HIV R80A 184 188 Vpr 70 73 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Interestingly, the peptides with mutation of Arg-80 (Vpr75-90 R80A and Vpr75-90 (R76Q, V83I, R80A, T84I)) showed the lowest binding response (Figure 2). 2011 BMC structural biology Result HIV R76Q;R80A;T84I;V83I 81;93;99;87 85;97;103;91 Vpr;Vpr 53;71 56;74 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Mutation of Arg-80 with Ala does not influence the weak secondary structure of the C-terminal binding domain of Vpr. 2011 BMC structural biology Result HIV R80A 12 27 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Mutation of Arg-80 with Ala significantly reduces the binding affinity. 2011 BMC structural biology Result HIV R80A 12 27 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Reduced binding affinity was also observed for the mutant peptide Vpr75-90 (R76Q, V83I, T84I) where Arg-80 was conserved (Figure 2), demonstrating the importance of an intact 16 residue C-terminal binding domain of Vpr. 2011 BMC structural biology Result HIV R76Q;T84I;V83I 76;88;82 80;92;86 Vpr;Vpr 66;215 69;218 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. reported that both mutants Vpr P35N and Vpr R80A failed to coprecipitate with CypA, which implies that simultaneous binding of CypA to both binding sites of Vpr is required for CypA to bind to full length Vpr. 2011 BMC structural biology Result HIV P35N;R80A 31;44 35;48 Vpr;Vpr;Vpr;Vpr 27;40;157;205 30;43;160;208 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. To reveal whether or not the R80A mutation influences the secondary structure of the binding domain, NMR spectra of wt Vpr75-90 and Vpr75-90 R80A dissolved in aqueous solution in the presence of 100 mM dodecylphosphocholine (DPC) were recorded and chemical shift index (CSI) were performed. 2011 BMC structural biology Result HIV R80A 29 33 Vpr;Vpr 119;132 122;135 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. Also, the consensus of the test sequences of the PR revealed one difference (T13I) between the global subtype C consensus and three positions (T19I, R20K and D35E) with regard to the South African reference sequence (figures not shown). 2012 Archives of virology Result HIV D35E;R20K;T13I;T19I 158;149;77;143 162;153;81;147 PR 49 51 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. Comparison of the amino acid consensus sequence of the V3 loop showed it was identical in all positions except at Q32E to the global consensus sequences of subtypes C and B. 2012 Archives of virology Result HIV Q32E 114 118 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. For the RT gene, the K103N substitution, which confers primary resistance to NNRTIs such as nevirapine was present in two of 44 sequences (4.5%) (samples 07M5ZA and 07V2ZA). 2012 Archives of virology Result HIV K103N 21 26 NNRTI;RT 77;8 83;10 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. However, differences were observed at six positions (I60V, G123F, V174A, K175Q, P277R and T286A) when compared to the South African reference sequence. 2012 Archives of virology Result HIV G123F;I60V;K175Q;P277R;T286A;V174A 59;53;73;80;90;66 64;57;78;85;95;71 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. The amino acid alignments of the gag p17 and p24 showed no difference between their consensus sequences and the global subtype C consensus sequence, but they differed from the South African vaccine strain at seven positions (E11G, K15A, H27Q, I34L, M61I, K75R, and C111S) for the gag p17 and four positions (I91V, N125S, V129I and R151K) in the gag p24 region. 2012 Archives of virology Result HIV C111S;E11G;H27Q;I34L;I91V;K15A;K75R;M61I;N125S;R151K;V129I 265;225;237;243;308;231;255;249;314;331;321 270;229;241;247;312;235;259;253;319;336;326 p24;p24;Gag;Gag;Gag 45;349;33;280;345 48;352;36;283;348 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. A per-residue basis decomposition investigation shows that the I50L/A71V mutant directly increases the binding affinity by approximately -0.88 (Ile50 to Leu50) and -0.90 (Ile50' to Leu50') kcal/mol, accounting 45% for the total gain of the binding affinity. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50L 68;144;63 72;158;67 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. According to Figure 6a, in chain-A for WT and I50V there is considerable overlapping of the two distributions, whereas for I50L/A71V-HIV-pr the distribution is quite different from those of WT and I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V;I50V 128;123;46;197 132;127;50;201 PR 137 139 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. According to Figures 17b-d, these enhancements are also consistent with the shortest distances of C-O10, C-O9, and C-O22 for Gly49', Leu50 and Leu50'of I50L/A71V-HIV-pr, respectively, as compared to those of WT and I50V-HIV. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 157;152;215 161;156;219 PR 166 168 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. According to Table 3, the occupancy of these four H-bonds is higher than 88% except for the bond between the Val50' and WAT301 in case of the I50V mutant, where the occupancy is ~70%. 2012 The journal of physical chemistry. B Result HIV I50V 142 146 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. According to TGBTOT in Table 2 and Figure 15, the I50V mutant directly reduces the binding affinity by approximately 0.21 (Ile50 to Val50) and 0.39 (Ile50' to Val50') kcal/mol, which only accounts 18% for the total loss of the binding affinity. 2012 The journal of physical chemistry. B Result HIV I50V;I50V 123;50 137;54 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. According to the data obtained for the RMSD values of the three complexes, WT complex has a higher mean (1.27 A) than the I50V mutant (1.22 A) and I50L/A71V double mutant (1.14 A), with a respective deviation of 0.16, 0.15 and 0.13 A. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 152;147;122 156;151;126 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Although Yanchunas et al showed that the mutant I50L/A71V exhibits increased binding to a number of protease inhibitors (except for atazanavir) relative to wild-type enzymes, there is no report on the effect of the double mutant on the HIV-pr's binding to TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 53;48 57;52 PR;PR 100;240 108;242 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Analyzing the frequency distribution plot (Figure 7d) for the other TriCa angle Gly49-Ile50-Gly51, it can also be found that the I50V mutant structures have different conformations as compared to WT and I50L/A71V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 208;203;129 212;207;133 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Analyzing the frequency distribution plot for the TriCa angle 48-49-50, it was found that the distribution of the angle for WT and I50L/A71V overlaps substantially; however, the I50V distribution shows a difference as compared to the other two. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 136;131;178 140;135;182 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. As shown in Table 1, the experimental binding affinity difference between WT and I50V-HIV was 1.3-3.30 kcal/mol, which was determined to induce rather different performance to the TMC. 2012 The journal of physical chemistry. B Result HIV I50V 81 85 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. As shown in the figure and table, the binding free energies of WT, I50V and I50L/A71V complexes are -15.33, -10.88 and -18.65 kcal/mol respectively, which suggests that the I50L/A71V double mutant HIV-pr has the strongest binding to the TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;A71V;I50L;I50L;I50V 81;178;76;173;67 85;182;80;177;71 PR 201 203 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Besides the direct effect from the residues Leu50 and Leu50', the residue Gly49' considerably increases the binding affinity of I50L/A71V-HIV-pr to the inhibitor by -0.74 kcal/mol, to which the electrostatic interaction of Leu50's backbone contributes by -1.23kcal/mol. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 133;128 137;132 PR 142 144 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Besides the direct effects from the residues Leu50 and Leu50', the residue Gly49' considerably increases the binding affinity of I50L/A71V-HIV-pr to the inhibitor by -0.74 kcal/mol, to which the electrostatic energy of Leu50's backbone contributes by -1.23kcal/mol. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 134;129 138;133 PR 143 145 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Compared to the WT and I50V mutant, the I50L/A71V HIV-pr has less stability of the H-bonding between the Asp29, Asp30 with the O26 and O28 of bis-THF group. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 45;40;23 49;44;27 Asp;Asp;PR 105;112;54 108;115;56 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Contributions of the binding free energies of complexes WT, I50V and I50L/A71V are summarized in the Table 1 and Figure 14. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 74;69;60 78;73;64 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Figure 18d confirms that the C...O22 for I50V-HIV-pr is longer than those for WT and I50L/A71V-HIV-pr (4.1 vs 3.6A). 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 90;85;41 94;89;45 PR;PR 50;99 52;101 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Figure 7 shows the time series plot for angle Gly48-Gly49-Ile50 Calpha atoms, where TriCa angle seems to be more stable for I50L/A71V-HIV-pr than those for the WT- and I50V-HIV-pr. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 129;124;168 133;128;172 PR;PR 138;177 140;179 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Figure S1 in supporting information shows the RMSD plots for all (WT, I50V and I50V/A71V) apo type HIV-pr, and indicates that the conformations for all apo type have also achieved equilibrium. 2012 The journal of physical chemistry. B Result HIV A71V;I50V;I50V 84;70;79 88;74;83 PR 103 105 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For both the apo and complexed HIV-pr, the analysis indicates many intriguing effects due to the double mutant, I50L/A71V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 117;112 121;116 PR 35 37 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For example, L90M and V82F/I84V mutations open the flap a bit more in the mutant than the WT, whereas M46I mutation makes the flap more closed. 2012 The journal of physical chemistry. B Result HIV I84V;L90M;M46I;V82F 27;13;102;22 31;17;106;26 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For Ile50/50' and Val50/50', although the main driving force to the binding is van der Waals energy with a small unfavorable DeltaGpol in cases of WT-TMC and I50V-TMC (Figures 16a and 16b), a favorable DeltaGpol along with the van der Waals energy plays important roles in binding of TMC114 to I50L/A71V double mutant (Figure 16c). 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 299;294;158 303;298;162 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For the case of double mutant I50L/A71V, all the energy components are more favorable for its binding to TMC114 except for the polar solvation energy DeltaGpb and TDeltaS of the system relative to the WT complex. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;A71V;I50L 36;31;35;30 40;35;39;34 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For the double mutant, the distribution has one peak around 6 A, whereas for WT and I50V mutant the main peak locates around 6 A, and the other minor around 7-8 A region. 2012 The journal of physical chemistry. B Result HIV I50V 84 88 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. For the mutation from Ile50 to Leu50, the binding enhancement can be mainly attributed to the electrostatic by -1.05kcal/mol and van der Waals by -0.38 kcal/mol, yet considerably being compromised by the increase of the polarization energy of 0.58 kcal/mol; whereas from Ile50' to Leu50' the contribution from the electrostatic is only -0.24 kcal/mol and the van der waals term is significant by -0.48kcal/mol. 2012 The journal of physical chemistry. B Result HIV I50L 22 36 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. From the time series plot of distance between Asp25 OD1-TMC O18 (Figure 12), it was found to be almost always constant for WT (mean of 2.64 A) and I50V (mean of 2.72 A) as compared to their initial crystal structure distance of 2.58 A and 2.59 A, respectively. 2012 The journal of physical chemistry. B Result HIV I50V 147 151 Asp 46 49 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Hence, on the basis of above structural energetic analysis discussed, we can conclude that the direct effects from Val50 and Val50', e.g., the decrease in van der Waals for both residues and the increase in polar solvation energy for Val50', with a few other residues Gly49, Ala28' and Asp30' accomplish the drug resistance in I50V mutant. 2012 The journal of physical chemistry. B Result HIV I50V 327 331 Asp 286 289 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Hence, the mean of the double mutant structure is significantly less (1.15 A) than the WT, suggesting that there is a close movement of flaps in I50L/A71V as compared to WT- and I50V-HIV-pr structures and probably making the active site volume smaller. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 150;145;178 154;149;182 PR 187 189 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Hence, the SD of I50V is much higher than the WT and especially than the I50L/A71V, which is an indication of the higher mobility of the flap tips in case of I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V;I50V 78;73;17;158 82;77;21;162 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. However, for the double mutant I50L/A71V, the distance was observed to be quite close between the two atoms from the beginning to up to ~3.7 ns (except around 0.57 ns to 1.1 ns), but eventually around 4 ns the distance goes high up to 4.8 A. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 36;31 40;35 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. However, the double mutant I50L/A71V-HIV-pr displays an enhanced binding to the inhibitor relative to the WT HIV-pr. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;A71V;I50L 33;28;32;27 37;32;36;31 PR;PR 41;113 43;115 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. However, the I50V mutant spends more time in the lower values in the initial, but eventually overlaps with the WT in the end. 2012 The journal of physical chemistry. B Result HIV I50V 13 17 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. I50V mutation shows a binding decrease due to electrostatic energy by about 3.17 kcal/mol and van der Waals energy by1.09 kcal/mol relative to the WT, complementing the resistance of I50V to TMC114. 2012 The journal of physical chemistry. B Result HIV I50V;I50V 183;0 187;4 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In both chains for I50V-HIV-pr, Arg8 has a higher mobility as compared to WT and I50L/A71V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 86;81;19 90;85;23 PR 28 30 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In contrast to the distance from OD1 to O18 of TMC114, Figure 12(b) shows that for double mutant I50L/A71V, the distance from OD2 to O18 eventually tends to be stable at 2.4A with much shorter average (2.85 A) than another two cases (4.03 for WT and 3.94 for I50V). 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 102;97;259 106;101;263 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In general for all proteases (WT, I50V and I50L/A71V) the average flap tip-active site distance in chain-B is longer than that of chain-A. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 48;43;34 52;47;38 PR 19 28 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In line with the more opening of apo I50V-HIV-pr, the entropy effect decreases the binding affinity more than WT by 1.19 kcal/mol. 2012 The journal of physical chemistry. B Result HIV I50V 37 41 PR 46 48 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In line with the previous studies, as compared with the WT HIV-pr the decrease of the binding affinity of I50V-HIV-pr to TMC114 was confirmed. 2012 The journal of physical chemistry. B Result HIV I50V 106 110 PR;PR 63;115 65;117 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In line with the previous studies, the binding affinity of the mutation I50V to TMC114 decreases by 4.45 kcal/mol compared to the WT complex, resulting in the drug resistance to the inhibitor; however, for the double mutation I50L/A71V complex the binding affinity is increased by 3.32 kcal/mol. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 231;226;72 235;230;76 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In order to get insights to the contribution spectrum of binding energy for TMC114, with WT, I50V mutant and I50L/A71V double mutant, absolute binding free energies are calculated for all the complexes using the MM-PBSA method. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 114;109;93 118;113;97 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In the crystal structure of the three proteases WT, I50V and I50L/A71V, residues in the flap tip most Ile50/Val50/Leu50 do not have direct polar interactions with the TMC114 in 3 A regions. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 66;61;52 70;65;56 PR 38 47 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In the I50L/A71V double mutant HIV-pr, the isoleucine-to-leucine substitution places the methyl group in a different position without significant change in the conformation of the side chain. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 12;7 16;11 PR 35 37 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. In the I50V mutant HIV-pr, the replacement of isoleucine with valine results in a loss of methyl group, which apparently decreases the interaction with the central phenyl of TMC 114 through C-H...pi, the size of the hydrophobic side chain and possible increase of the size of the active site with a reduced binding affinity to TMC114. 2012 The journal of physical chemistry. B Result HIV I50V 7 11 PI;PR 196;23 198;25 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. It is clearly seen that with respect to (I50-I50') Calpha distance, WT and I50V mutant assembles two different types of structures as compared with the I50L/A71V double mutant. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 157;152;75 161;156;79 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. It is noted that, the change from Ala71 to Val71 in the cantilever region of the HIV-pr has not affected much the H-bond pattern, which can be seen with >= 90% occupancy. 2012 The journal of physical chemistry. B Result HIV A71V 34 48 PR 85 87 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. It was found from the crystal structure of double mutant I50L/A71V, that the distance is 2.58 A, while the obtained MD result has a mean of 3.84 A. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 62;57 66;61 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Looking at the distribution plot for the TriCa angle in Figure 11, we observed that the I50V and I50L/A71V mutant complexes have a single peak around ~110 and ~95 , respectively; while the WT has two peaks: the main peak at around 95 and ~130 is the other one. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 102;97;88 106;101;92 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Moreover, chain-B (Figure 6b) also displays different conformational sampling for I50L/A71V as compared to WT and I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 87;82;114 91;86;118 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Moreover, the distributions for WT-, I50V- and I50L/A71V-HIV-pr/TMC114 complexes have significant overlap (Figure 9a). 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 52;47;37 56;51;41 PR 61 63 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Regardless of the change in residues from isoleucine to valine in I50V or isoleucine to leucine in I50L/A71V, the mutations do not have a greater impact on the stability of the function of WAT301. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 104;99;66 108;103;70 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Residues Gly16 and Gly17 in both chains for WT have significant higher mobility than the mutant duo I50V and I50L/A71V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 114;109;100 118;113;104 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Table 2 and Figure 15 show that, besides the direct effects from the residues Val50 and Val50', the residues Gly49, Ala28' and Asp30' also considerably decrease the binding affinity of I50V-HIV-pr to the inhibitor by 0.29, 0.16 and 0.21 kcal/mol, respectively, accounting approximately another 20% for the total binding loss. 2012 The journal of physical chemistry. B Result HIV I50V 185 189 Asp;PR 127;194 130;196 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Table 2 further shows that the I50L/A71V mutant directly increase the binding affinity by approximately -0.88 (Ile50 to Leu50) and -0.90 (Ile50' to Leu50') kcal/mol, which accounts 45% for the total gain of the binding affinity. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50L 36;111;31 40;125;35 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The average B-factor per residue in the flap and active site binding region for the WT-, I50V- and I50L/A71V-HIV-pr/TMC114 complexes are 31.03, 29.11 and 28.08 A2, respectively. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 104;99;89 108;103;93 PR 113 115 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The average flap tip - active site, flap -flap distances and curling behavior of the TriCa angles suggests a closer movement of flaps in the double mutant as compared to WT and I50V, probably making the active site volume smaller. 2012 The journal of physical chemistry. B Result HIV I50V 177 181 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The change in H-bonding for I50L/A71V HIV-pr results in a reduction of polarity energies (Eele+TGB) of residue Asp30' by about 0.58 kcal/mol compared to the WT case (Figure 5c). 2012 The journal of physical chemistry. B Result HIV A71V;I50L 33;28 37;32 Asp;PR 111;42 114;44 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The difference between the complexed WT, I50V and I50L/A71V HIV-pr was found to be less and narrower than that of the apo HIV-pr (Figure 10). 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 55;50;41 59;54;45 PR;PR 64;126 66;128 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The distribution is almost overlapped for WT and I50L/A71V and is clearly different from that of I50V mutant. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 54;49;97 58;53;101 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The distribution is quite different as compared to the apo structures, where WT and I50L/A71V mutant partially overlapped and is clearly different from I50V mutant (Figure 7d). 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 89;84;152 93;88;156 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The double mutant I50L/A71V results in binding enhancement in terms of electrostatic energy and van der Waals by about -5.52 and -0.42 kcal/mol in the gas phase, and binding decrease in DeltaGpb by about 2.0 kcal/mol and TDeltaS by about 1.06 kcal/mol relative to the WT. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 23;18 27;22 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The energy decomposition analysis suggests that the increase of the binding affinity for the double mutant I50L/A71V can be mainly attributed to the increase in electrostatic and van der Waals energies, which are cancelled out in part by the increase of polar solvation energy. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 112;107 116;111 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The enhanced binding affinity implies that the double mutant I50L/A71V may be well adapted by the TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 66;61 70;65 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The flap dynamics of the inhibitor bound proteases can be further analyzed by the TriCa angles in the flap tip region for all three WT-, I50V- and I50L/A71V-HIV-pr complexes. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 152;147;137 156;151;141 PR;PR 41;161 50;163 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The flexibility of the apo-protein in chain-A is greater in case of I50V, particularly in the flap regions. 2012 The journal of physical chemistry. B Result HIV I50V 68 72 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The flip-flop interactions justifies that the inhibitor is always bound to either of the OD1/OD2 atoms of Asp25, making the binding stronger in I50L/A71V as compared to WT and I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 149;144;176 153;148;180 Asp 106 109 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The flip-flop interactions justifies that the inhibitor tries to bind to either of the OD1/OD2 atoms of Asp25 in I50L/A71V, which seems to be different from that of WT and I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 118;113;172 122;117;176 Asp 104 107 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The increase of the binding implies that the double mutant I50L/A71V may be well adapted by the TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 64;59 68;63 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean and SD of I50V (I50L/A71V) are14.49 (14.43) A and 0.58 (0.47) A, respectively; while for the WT, the mean and SD are only 14.94 A and 0.53 A, respectively. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 30;25;19 34;29;23 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean and SD of the TriCa angle for WT (I50L/A71V) distribution are 97.65 (96.55) and SD is 6.85 (4.81), respectively, whereas for the single mutant I50V the mean and SD are 105.58 and 9.62 . 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 48;43;154 52;47;158 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean and SD of the TriCa angle Gly48-Gly49-Ile50 are 138.91 and 8.99 for WT distribution, 136.26 and 10.44 for I50V, and 142.59 and 6.13 for I50L/A71V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 156;151;119 160;155;123 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean and SD of WT (I50V) are 14.62 (14.20) A and 0.98 (1.04) A, respectively; whereas for the double mutant I50L/A71V the mean and SD are only 13.51 A and 0.83 A, respectively. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 117;112;23 121;116;27 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean and SD of WT (I50V) are 14.84 (14.02) A and SD is 0.87 (0.70) A respectively. 2012 The journal of physical chemistry. B Result HIV I50V 23 27 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean and standard deviation (SD) of WT distribution are 7.0 A and 0.92 A, of I50V mutant are 6.45 A and 0.8 A and those of double mutant are 5.85 A and 0.37 A, respectively. 2012 The journal of physical chemistry. B Result HIV I50V 81 85 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean for flap tip-active site residue are 14.19, 14.09 and 14.30 and the SD values are 0.41, 0.37, and 0.41 for WT-, I50V- and I50L/A71V-HIV-pr/TMC114, respectively. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 136;131;121 140;135;125 PR 145 147 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean of the distribution for I50L/A71V is smaller by 1.11 A than WT and 0.69 A than I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 38;33;88 42;37;92 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean values of the TriCa angle for WT (I50V) distribution are 107.19 (110.54 ) and SD is 14.33 (5.06 ), whereas for the double mutant I50L/A71V the mean and SD are 96.30 and 4.90 . 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 145;140;43 149;144;47 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mean values of WT and I50V are larger than that of double mutant I50L/A71V complex by ~11 and > 14 , which implies the more curling out of the flap tips in WT and I50V than the double mutant. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V;I50V 74;69;26;168 78;73;30;172 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The mutation of Ala71 to valine requires more space to accommodate valine's bulkier side chain, which is oriented towards the enzyme interior. 2012 The journal of physical chemistry. B Result HIV A71V 16 31 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The present results for the WT- and I50V-HIV-pr/TMC114 agree well with the available experimental affinities (-15.20, and -11.90 kcal/mol). 2012 The journal of physical chemistry. B Result HIV I50V 36 40 PR 45 47 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The present results show that the binding affinity of the double mutant I50L/A71V is different from that of WT by -3.32 kcal/mol (-0.6 kcal/mol after taking error bars), and from that of the I50V by -7.8 kcal/mol (-6.7 kcal/mol after error bars), which will lead to different performance to the TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 77;72;191 81;76;195 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The reduced active site conformations of I50L/A71V due to the flap dynamics behavior may enhance the binding of an inhibitor to the active site region. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 46;41 50;45 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The relatively smaller B-factor of the double mutant I50L/A71V-complex may be explained by the relatively less conformational fluctuations and decreased flexibility. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 58;53 62;57 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The results indicate that the mutant I50V induces weaker binding to TMC114, whereas the double mutant I50V/A71V enhances the binding affinity to TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;I50V;I50V 107;37;102 111;41;106 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The results indicate the smaller distance between the active site to flap residues in I50L/A71V than in WT and I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 91;86;111 95;90;115 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The RMSD plots indicate that the conformations of the WT, single mutant (I50V) and double mutant (I50L/A71V) HIV-pr complexes are in good equilibrium. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 103;98;73 107;102;77 PR 113 115 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The secondary mutation A71V does not have much direct effect on the binding. 2012 The journal of physical chemistry. B Result HIV A71V 23 27 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The time series plot (Figure 7b) also shows the higher fluctuations of I50V structures as compared to WT and I50L/A71V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 114;109;71 118;113;75 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The trajectory of the I50V-HIV/TMC114 complex fluctuates more than other two trajectories at around 3-5 ns, after that it goes parallel to each other. 2012 The journal of physical chemistry. B Result HIV I50V 22 26 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Therefore the mean of the distribution for WT differ by approximately 0.5 A from I50L/A71V and I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 86;81;95 90;85;99 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Therefore the mean of the two distributions of WT and I50L/A71V differ by ~8 and ~9 from that of I50V mutant with wider value coverage for I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V;I50V 59;54;99;141 63;58;103;145 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. These results reveal that the distances between the flap tip and catalytic site in chains A and B are clearly different for the double mutant I50L/A71V structures with smaller distance values compared to the WT and I50V mutant structures. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 147;142;215 151;146;219 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. This may be due to the effect of the mutation A71V from the double mutant, where the change from Ala71 to Val modifies the H-bonding pattern between the four anti-parallel beta-sheets connecting Asp25 site to Val71. 2012 The journal of physical chemistry. B Result HIV A71V;A71V 46;97 50;109 Asp 195 198 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. This observation suggests that WAT301 hardly involve in the resistance of both I50V single and I50L/A71V double mutant to TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 100;95;79 104;99;83 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. This result also complements with the tip-tip distance that suggests a close movement of flaps in I50L/A71V as compared to WT and I50V structures, probably making the active site smaller in volume. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 103;98;130 107;102;134 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. This result confirms that, mutation A71V does not have direct influence on the active site conformation and binding affinity. 2012 The journal of physical chemistry. B Result HIV A71V 36 40 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. This result is quite similar to the earlier study on JE-2147 bound I47V mutant. 2012 The journal of physical chemistry. B Result HIV I47V 67 71 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Thus, finally it was noted that the I50V simulation samples different structures as compared to the WT and double mutant with respect to the flap tips mobility and curling, which is confirmed by the higher SD of both TriCa angles in the I50V-HIV-pr. 2012 The journal of physical chemistry. B Result HIV I50V;I50V 36;237 40;241 PR 246 248 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Thus, the loss of H-bonding between TMC114 and the side chain of Asp30 (Asp29) and the polar solvation energies for Asp30' indirectly relate to the binding of I50L/A71V HIV-pr to TMC114. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 164;159 168;163 Asp;Asp;Asp;PR 65;72;116;173 68;75;119;175 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Thus, the lowest flexibility of I50L/A71V implies that the I50L/A71V-HIV-pr may have the highest binding affinity to TMC114 and tends to have the least drug resistance behavior. 2012 The journal of physical chemistry. B Result HIV A71V;A71V;I50L;I50L 37;64;32;59 41;68;36;63 PR 73 75 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Thus, the mean of the distribution for I50L/A71V in chain B differ by ~1.7 A from WT and ~ 0.9 A from I50V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 44;39;102 48;43;106 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. Whereas, for the double mutant I50L/A71V the mean and SD are 13.14 A and 1.04 A, respectively. 2012 The journal of physical chemistry. B Result HIV A71V;I50L 36;31 40;35 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. While considerable overlaps exist in the three distributions, the distance between the flap tips were recognized to fluctuate more in the case of WT and I50V than in the double mutant I50L/A71V. 2012 The journal of physical chemistry. B Result HIV A71V;I50L;I50V 189;184;153 193;188;157 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. All three subjects failing the NLF-based regimen had the M184V mutation and the two with prior sdNVP exposure also had NNRTIs mutations (K103N, V106M n=1; K103N, Y188H n=1). 2012 Antiviral therapy Result HIV K103N;K103N;M184V;V106M;Y188H 137;155;57;144;162 142;160;62;149;167 NNRTI 119 125 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. At time of failure the following NRTI mutations were observed: A62V (n=1; 1%), K65R (n=2; 3%), D67G/N (n=2; 3%), T69L (n=1; 1%), K70R (n=1; 1%), V75I (n=1; 1%), M184V (n=46; 66%) and K219K (n=1; 1%). 2012 Antiviral therapy Result HIV A62V;D67G;D67N;K219K;K65R;K70R;M184V;T69L;V75I 63;95;95;183;79;129;161;113;145 67;101;101;188;83;133;166;117;149 NRTI 33 37 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Both the K103N and V106M mutations occurred more frequently in EFV- than NVP-exposed subjects, but differences were not significant (51% vs. 2012 Antiviral therapy Result HIV K103N;V106M 9;19 14;24 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Of the five with resistance at enrollment, no NRTI resistance was observed, two had resistance to NNRTIs (K103N n=1; V106M, K103N n=1), two had protease resistance (M46I n=1, M46L n=1) and one had both protease and NNRTI resistance (M46V, K101E, G190A). 2012 Antiviral therapy Result HIV G190A;K101E;K103N;K103N;M46I;M46L;M46V;V106M 246;239;106;124;165;175;233;117 251;244;112;129;170;179;237;122 PR;PR;NNRTI;NNRTI;NRTI 144;202;98;215;46 152;210;104;220;50 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Of the remaining nine participants failing a LPV/r regimen, M184V was observed in one subject and K103N, V106A and Y188C in another female subject (with no previous sdNVP exposure reported). 2012 Antiviral therapy Result HIV K103N;M184V;V106A;Y188C 98;60;105;115 103;65;110;120 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Only one of these subjects with baseline resistance (M46I) would have been fully susceptible to the regimen they were prescribed (d4T, 3TC, EFV). 2012 Antiviral therapy Result HIV M46I 53 57 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Only one subject had TAMs and Q151M was not observed. 2012 Antiviral therapy Result HIV Q151M 30 35 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Protease resistance was only observed in one subject accessing LPV/r; however the M46L mutation was present at enrollment. 2012 Antiviral therapy Result HIV M46L 82 86 PR 0 8 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. TAMS were infrequent (1%) and Q151M was not observed (Figure 1). 2012 Antiviral therapy Result HIV Q151M 30 35 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The M184V mutation was the most frequent (n=47; 57%), followed by K103N (46%) and Y181C (21%). 2012 Antiviral therapy Result HIV K103N;M184V;Y181C 66;4;82 71;9;87 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The M184V mutation was the most prevalent mutation occurring in 46 subjects experiencing viral rebound (66%; 95% CI: 54%-76%) (Figure 2) followed by the K65R mutation. 2012 Antiviral therapy Result HIV K65R;M184V 153;4 157;9 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The most frequent mutation was K103N (n=3; 23%) followed by V106A/M (n=2; 15%). 2012 Antiviral therapy Result HIV K103N;V106A;V106M 31;60;60 36;67;67 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The Y181C and M184V mutations occurred in one subject each. 2012 Antiviral therapy Result HIV M184V;Y181C 14;4 19;9 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The Y181C and V106A mutations only occurred in participants accessing a failing NVP-containing regimen (41% and 9%, respectively). 2012 Antiviral therapy Result HIV V106A;Y181C 14;4 19;9 22331986 HIV Drug Resistance-Associated Mutations in Antiretroviral Naive HIV-1-Infected Latin American Children. There were 3 different mutations detected among the 6 subjects with DRMs: reverse transcriptase mutations K70R (detected in 3 subjects), K70E (detected in 2 subjects), and protease mutation I50 V (detected in a single subject). 2010 Advances in virology Result HIV I50V;K70E;K70R 190;137;106 195;141;110 RT;PR 74;172 95;180 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Additionally, the increase in CD4+ T cells was enhanced by the concomitant polymorphism N140I. 2012 Retrovirology Result HIV N140I 88 93 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Among these plasmids, 13 clones were derived from patient 9, containing an asparagine at position 140 (140 N) and the wild-type (wt) amino acid at position 38 (38 V) or an alanine at position 38 (38A) (n = 5 and n = 8, respectively); 19 clones were derived from patient 10, who contained the substitution N140T and the wt 38 V (n = 10) or the V38A mutation (n = 9); and finally, 16 clones were derived from patient 1, who had the polymorphism N140I and the wt amino acid at position 38 (n = 10) or the V38A mutation (n = 6, Figure 1). 2012 Retrovirology Result HIV N140I;N140T;V38A;V38A 443;305;343;502 448;310;347;506 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Because there were no significant differences in fusogenicity among the Envs tested in our assays, we specifically quantified Env-mediated cell death, since in vitro the single-amino-acid mutation V38A/E has been shown to alter this mechanism. 2012 Retrovirology Result HIV V38A;V38E 197;197 203;203 Env;Env 72;126 76;129 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Clinical findings have suggested that certain ENF-resistant mutants arising during salvage therapy, specifically, the cluster V38A+N140I, are associated with an increase in CD4+ cell counts, even after virological failure. 2012 Retrovirology Result HIV N140I;V38A 131;126 136;130 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Despite a similar fusogenic capacity of the wt recombinant Envs and those bearing mutations at position 38, the absolute loss of CD4+ T cells was significantly lower after exposure to Envs containing the V38A mutation in a N140I background than after exposure to wt Env (18.1% and 31.3%, respectively. 2012 Retrovirology Result HIV N140I;V38A 223;204 228;208 Env;Env;Env 59;184;266 63;188;269 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. However, in contrast to previously published data, when intra-patient analyses were performed, the fusogenic activities of all recombinant Envs obtained from each patient were similar, indicating that in a full-length gp41 background, the V38A mutation did not impair the cell-to-cell fusion activity of Env in the presence of the amino acids N, T or I at position 140 (Figure 3). 2012 Retrovirology Result HIV V38A 239 243 gp41;Env;Env 218;139;304 222;143;307 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. However, the acquisition of the V38A mutation in a gp41 background containing an N or T at position 140 had no significant impact on the pathogenicity of Env, again highlighting the importance of the genetic context on the function of Env. 2012 Retrovirology Result HIV V38A 32 36 gp41;Env;Env 51;154;235 55;157;238 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. However, when we analyzed the percentage of cells expressing the Env constructs obtained from the same patient by comparing clones displaying or not the V38A mutation (an intra-patient comparison after and before treatment, respectively), the Env expression was similar in all cases (Figure 2A). 2012 Retrovirology Result HIV V38A 153 157 Env;Env 65;243 68;246 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. In agreement with previously reported in vivo data, both the absolute loss of CD4+ T cells and Env-induced single cell death was significantly reduced for Envs that had the cluster of mutations V38A + N140I. 2012 Retrovirology Result HIV N140I;V38A 201;194 206;198 Env;Env 95;155 98;159 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. In agreement with this property, it has been described that single-amino-acid mutations in the ectodomain (V38A/E) or transmembrane regions of gp41 reduce cell-to-cell fusion activity of the virus. 2012 Retrovirology Result HIV V38A;V38E 107;107 113;113 gp41 143 147 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Most of the recombinant plasmids constructed from sequences obtained during ENF treatment carried the V38A mutation as the only change associated with ENF resistance, although four clones derived from the 140N patient carried the N42T mutation, and three others showed the N126K mutation. 2012 Retrovirology Result HIV N126K;N42T;V38A 273;230;102 278;234;106 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. None of the clones obtained from the patient carrying the N140I mutation in gp41 showed changes in the caveolin binding region, suggesting that the changes in the induction of bystander apoptosis observed in this study are not due to a defect in the binding of this protein to the gp41 protein. 2012 Retrovirology Result HIV N140I 58 63 gp41;gp41 76;281 80;285 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. The analysis of a caveolin-1 binding motif in the gp41 protein, which has been recently reported to affect HIV-1 pathogenesis, showed that only one plasmid from the patient harboring the 140N background carried an M to V substitution at position 115. 2012 Retrovirology Result HIV M115V 214 249 gp41 50 54 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. The lowest percentage of Env-positive cells was observed for the 140N constructs (mean = 11.40 +/- 3.9), whereas the highest percentage of Env-expressing cells was observed for the N140T clones (mean = 15.91 +/- 4.4) (Figure 2A). 2012 Retrovirology Result HIV N140T 181 186 Env;Env 25;139 28;142 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Thus, the impaired ability to deplete CD4+ T cells by the recombinant Envs that contained the cluster of mutations V38A+N140I in the gp41 protein was associated with a significant reduction in apoptosis induction on primary cells (13.4% and 7.4% for baseline and with the cluster of mutation samples, respectively; p = 0.031). 2012 Retrovirology Result HIV N140I;V38A 120;115 125;119 gp41;Env 133;70 137;74 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. When an inter-patient comparison was performed by grouping all of the Envs obtained from each patient irrespective of the time point, a significantly different percentage of Env-expressing cells was observed between plasmids constructed from the 140N- and N140T-carrying patients. 2012 Retrovirology Result HIV N140T 256 261 Env;Env 70;174 74;177 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. When an intra-patient analysis of this assay was performed, there were differences between the recombinant clones carrying the V38A mutation and the wt clones in an N140I background, while the clones bearing the N or T amino acids at position 140 showed similar apoptosis-inducing capacity when wt and V38A clones were compared (Figure 4B). 2012 Retrovirology Result HIV N140I;V38A;V38A 165;127;302 170;131;306 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Four patients had a K65R at virologic failure (variant range 0.52% to 1.28%), and none developed phenotypic resistance to TDF (Table S1). 2012 PloS one Result HIV K65R 20 24 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Nineteen of 24 (79.2%) had any PI, N(t)RTI and/or NNRTI resistance mutations; 18/24 (75%) had N(t)RTI mutations: M184V/I (11), TAMs(7) and K65R (4), and 9/24 (37.5%) had PI mutations: M46I/V(5), F53L(2), I50V(1), D30N(1) & N88S(1) (Figure 1b). 2012 PloS one Result HIV D30N;F53L;I50V;K65R;M184I;M184V;M46I;M46V;N88S 213;195;204;139;113;113;184;184;223 217;199;208;143;120;120;190;190;227 NRTI;NRTI;NNRTI;PI;PI 35;94;50;31;170 42;101;55;33;172 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Of the 12 specimens that had ultra deep sequencing of only the protease gene, 4/12 (33.3%) had low level PI mutations: F53L(2), L76V(1), I54S(1) and G73S(1) (Figure 1b). 2012 PloS one Result HIV F53L;G73S;I54S;L76V 119;149;137;128 123;153;141;132 PR;PI 63;105 71;107 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Of the seven patients with a M184V/I without phenotypic resistance to 3TC/FTC, the variant levels ranged from 0.42% to 31.1%. 2012 PloS one Result HIV M184I;M184V 29;29 36;36 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Out of 11 patients with M184V/I at virologic failure, 4 with M184V developed phenotypic resistance to FTC/3TC (variant range 95.93% to 100%; phenotypic range 57.54 to 75.63). 2012 PloS one Result HIV M184I;M184V;M184V 24;24;61 31;31;66 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Overall, 3/36 (8.3%) patients had PI mutations identified with Stanford-HIVdb weights >12 for ATV or LPV: 1 patient on ATV with N88S (0.43%-mutation load 1,828) and 2 patients on LPV: one with I50V (0.44%-mutation load 110) and the remaining patient with L76V (0.52%-mutation load 20). 2012 PloS one Result HIV I50V;L76V;N88S 193;255;128 197;259;132 PI 34 36 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. Secondary drug resistance was noted in all eight failing patients with NRTI (M184V, T215 complex) and NNRTI (K103N) being the most common mutations (figure 5). 2012 PloS one Result HIV K103N;M184V 109;77 114;82 NNRTI;NRTI 102;71 107;75 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A similar phenotype has been proposed for the A360V mutation; however, the biochemical analyses reported used RTs that also contained N348I. 2012 PloS one Result HIV A360V;N348I 46;134 51;139 RT 110 113 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A360V emerged in 2 of 5 participants who reached a study endpoint and in 4 of 18 participants who did not. 2012 PloS one Result HIV A360V 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Although each of the known TAMs was identified in one or more on-treatment samples, only the K70R and T215Y mutations were significantly associated with AZT monotherapy. 2012 PloS one Result HIV K70R;T215Y 93;102 97;107 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Among the 6 on-treatment samples that contained A360V, it was a pure mutant (100%) in 2 samples and a mixture (<50%) in 4 samples, as assessed by population sequencing (Table 2). 2012 PloS one Result HIV A360V 48 53 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Analysis of longitudinal samples in the 4 participants who did not reach study endpoint revealed that A360V generally emerged at the same time as TAMs, although in one participant it was the first mutation to emerge (Table 3). 2012 PloS one Result HIV A360V 102 107 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Importantly, when the A360V mutation was reverted to wildtype, statistically significant decreases in AZT resistance were observed for each of the virus pairs (Table 4). 2012 PloS one Result HIV A360V 22 27 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. In one of the participants who reached a study endpoint, A360V emerged at the same time as TAMs, however in the other participant it clearly emerged after TAMs (Table 3). 2012 PloS one Result HIV A360V 57 62 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. In this regard, we first assessed the AZT-MP excision activity of the wildtype, TAM-1 and TAM4-1/A360V enzymes on a well-defined DNA/DNA and RNA/DNA T/P substrate that is routinely used in our laboratory. 2012 PloS one Result HIV A360V 97 102 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Introduction of the A360V mutation into either wildtype or TAM-1 RT increased the enzyme's excision activity on the RNA/DNA T/P but not on the DNA/DNA T/P (Figure 1A, 1B). 2012 PloS one Result HIV A360V 20 25 RT 65 67 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Mechanism by which A360V confers AZT resistance. 2012 PloS one Result HIV A360V 19 24 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Of note, the A360V in the connection domain of HIV-1 RT was also significantly associated with AZT monotherapy and was more frequent than the M41L, D67N, L210W or K219E/Q mutations. 2012 PloS one Result HIV A360V;D67N;K219E;K219Q;L210W;M41L 13;148;163;163;154;142 18;152;170;170;159;146 RT 53 55 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Phenotypic analyses of HIV-1 containing A360V. 2012 PloS one Result HIV A360V 40 45 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Previous biochemical studies demonstrated that the N348I and Q509L mutations in HIV-1 RT indirectly increase AZT resistance by decreasing the frequency of secondary RNase H cleavages that reduce the RNA/DNA duplex length of the T/P and diminish the efficiency of AZT-MP excision. 2012 PloS one Result HIV N348I;Q509L 51;61 56;66 RT 86 88 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Taken together, these findings are consistent with the concept that A360V in HIV-1 RT impacts the efficiency of the AZT-MP excision reaction by an RNase H-dependent mechanism. 2012 PloS one Result HIV A360V 68 73 RT 83 85 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The A360V mutation was found to significantly reduce the frequency of a polymerase-independent cleavage event that decreases the RNA/DNA duplex to 10 nucleotides (Figure 1C, 1D). 2012 PloS one Result HIV A360V 4 9 Pol 72 82 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The connection domain mutation A371V was more frequent in last-on-therapy samples compared to pre-therapy samples, but this difference was not statistically significant (p = 0.25). 2012 PloS one Result HIV A371V 31 36 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The N348I and Q509L mutations were not detected in any of the 23 on-treatment samples. 2012 PloS one Result HIV N348I;Q509L 4;14 9;19 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Therefore, we performed biochemical experiments to probe the mechanism(s) by which A360V decreased AZT susceptibility. 2012 PloS one Result HIV A360V 83 88 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. To determine whether the A360V mutation conferred AZT resistance, we first cloned full-length RTs from participant samples 4, 11 and 29 into pxxLAI-3D, and selected a single clone for phenotypic analyses. 2012 PloS one Result HIV A360V 25 30 RT 94 97 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. To further confirm the role of A360V in AZT resistance, we generated 5 site-directed mutant viruses in pxxLAI that contained A360V in 2 different backgrounds of TAMs (TAM-1 and D67N/K70R). 2012 PloS one Result HIV A360V;A360V;D67N;K70R 31;125;177;182 36;130;181;186 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. When A360V was in the context of TAM-1 or D67N/K70R, AZT resistance increased 1.9- and 2.1- fold, respectively (p<0.05). 2012 PloS one Result HIV A360V;D67N;K70R 5;42;47 10;46;51 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. 5) carried resistant virus against AZT (K70R) and NVP (K103N) 4-6 weeks after birth; the mutation K70R was also detectable in the maternal delivery sample. 2012 PloS one Result HIV K103N;K70R;K70R 55;40;98 60;44;102 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Additional mutations in the HIV-1 genome were detected in three women: One woman each harbored the V106A (together with K103N, Y181C and M184V), the K65R (together with T215F) and the G190A (together with Y181C) mutation, respectively (Table 3, nos. 2012 PloS one Result HIV G190A;K103N;K65R;M184V;T215F;V106A;Y181C;Y181C 184;120;149;137;169;99;127;205 189;125;153;142;174;104;132;210 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Genotypic mutations associated with decreased susceptibility to AZT were detected in 11/50 (22%) women (7/50 (14%) containing K70R alone and 4/50 (8%) with T215Y/F mutation) whereas 9/50 (18%) women harbored NVP-resistant virus (K103N and/or Y181C). 2012 PloS one Result HIV K103N;K70R;T215F;T215Y;Y181C 229;126;156;156;242 235;130;163;163;247 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. If the calculated proportion of drug-resistant HIV-1 fell below the calculated threshold, it was considered to be false positive and presence of HIV-1 wild type was assumed; this affected the detection of K103N and T215Y only once. 2012 PloS one Result HIV K103N;T215Y 205;215 210;220 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. In 4/50 (8%) women a 3TC-resistance mutation (M184V) was identified, of these 3/50 (6%) developed drug-resistant HIV-1 strains against more than one drug (Figure 1). 2012 PloS one Result HIV M184V 46 51 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. NVP resistance mutations K103N and/or Y181C were detected in postpartum samples of nine (18%) women, but the proportion of resistant variants never exceeded 5% during the study period in 7/9 (78%) of these women. 2012 PloS one Result HIV K103N;Y181C 25;38 30;43 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. One woman displayed both AZT resistance mutations K70R and T215F in the viral genome, which were present already at delivery and persisted throughout the observation period at low frequencies (Table 3, no 5). 2012 PloS one Result HIV K70R;T215F 50;59 54;64 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Some maternal ASPCR results had to be excluded from analysis due to polymorphisms in primer binding sites (details in Materials and Methods S1); this affected two women for K103N analysis, one woman for Y181C analysis and six women for K70R analysis. 2012 PloS one Result HIV K103N;K70R;Y181C 173;236;203 178;240;208 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. T215Y and T215F mutations mostly emerged later and were measurable 1-6 weeks postpartum in 4/50 (8%) women in low proportions of 0.5%-3.9%. 2012 PloS one Result HIV T215F;T215Y 10;0 15;5 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. The 3TC-resistance mutation M184V was detected in four women (8%) in low proportions of 0.6%-1.0% and was no longer detectable in 3/4 women at week 12-16. 2012 PloS one Result HIV M184V 28 33 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. The first AZT-selected mutation emerging was the K70R, which was detectable at delivery in 5/50 women in proportions of 2%-28%. 2012 PloS one Result HIV K70R 49 53 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. The lower detection limit for evidence of minor drug-resistant HIV-1 variants was 0.99% for K70R, 0.04% for K103N (AAC), 0.01% for K103N (AAT), 0.35% for Y181C, 0.63% for M184V, 0.33% for T215Y and 0.42% for T215F (Table 2). 2012 PloS one Result HIV K103N;K103N;K70R;M184V;T215F;T215Y;Y181C 108;131;92;171;208;188;154 113;136;96;176;213;193;159 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. The range of proportions of drug-resistant HIV-1 variants was 0.2-36% for K103N mutants, 0.4-20% for Y181C mutants, 0.6-1.0% for M184V mutants, 2.0-28% for K70R mutants, 0.5-3.9% for T215Y mutants and 0.5-0.8% for T215F mutants, respectively. 2012 PloS one Result HIV K103N;K70R;M184V;T215F;T215Y;Y181C 74;156;129;214;183;101 79;160;134;219;188;106 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. The shortest interval between the start of AZT prophylaxis and detection of the K70R mutation was 28 days (Table 3, no 3). 2012 PloS one Result HIV K70R 80 84 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. We also checked population sequences for additional AZT/3TC/NVP-selected resistance mutations like M41L, D67N, K70R, L210W, T215Y/F and K219QE for AZT, K65R for 3TC and L100I, K101P, V106A/M, V108I, Y188C/L/H and G190A for NVP. 2012 PloS one Result HIV D67N;G190A;K101P;K219E;K219Q;K65R;K70R;L100I;L210W;M41L;T215F;T215Y;V106A;V106M;V108I;Y188C;Y188H;Y188L 105;213;176;136;136;152;111;169;117;99;124;124;183;183;192;199;199;199 109;218;181;142;142;156;115;174;122;103;131;131;190;190;197;208;208;208 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Endogenous polyubiquitination is also evident in Vpx K68A and K77A lanes. 2012 Virology Result HIV K68A;K77A 53;62 57;66 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. However, for TA, K68A, and K77A Vpx mutants, the early RT products were decreased 3.9, 1.8, and 3.4 -fold compared to Wt Vpx. 2012 Virology Result HIV K68A;K77A 17;27 21;31 RT 55 57 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. In contrast, for Vpx K84A, the amounts of early RT product were comparable to those for ES virus and pESdelX trans complemented with Vpx Wt (Fig 6). 2012 Virology Result HIV K84A 21 25 RT 48 50 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. In contrast, Vpx K84A interacted with DCAF1 comparably to Wt Vpx. 2012 Virology Result HIV K84A 17 21 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Several higher molecular weight bands that are observed with all Vpx mutants are presumed to be ubiquitinated cellular proteins that interact with Vpx and proteins that non-specifically bind to Ni-NTA beads (compare lane with FlagUbK48R to lane with Vpx Wt/FlagUbK48R). 2012 Virology Result HIV K48R 263 267 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. The 23 kDa band is present in lanes with Vpx Wt, K68A, and K77A, representing Vpx that is ubiquitin-modified, however this 23 kDa band is absent with the TA and K84A Vpx. 2012 Virology Result HIV K68A;K77A;K84A 49;59;161 53;63;165 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. The 23 kDa band represents ubiquitination of Wt, K68A, and K77A Vpx mutants, but it is not present with K84A Vpx or TA Vpx mutant. 2012 Virology Result HIV K68A;K77A;K84A 49;59;104 53;63;108 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. The K84A mutation did not affect the levels of early or late RT products 24h or 48h after infection, in comparison to ES virus. 2012 Virology Result HIV K84A 4 8 RT 61 63 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. The quantities of late RT products at 24h and 48h time point Vpx TA, K68A, and K77A were decreased 19, 12, 24 -fold compared to that for the ES virus and 12, 8, 16-fold compared to that with pESdelX trans complemented with Vpx Wt, respectively. 2012 Virology Result HIV K68A;K77A 69;79 73;83 RT 23 25 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. The ubiquitin K48R, which is deficient in the formation of polyubiquitin chains at position K48, and thus lacks the ability to tag substrates for proteasomal degradation, was used to enrich Vpx that is ubiquitin-modified. 2012 Virology Result HIV K48R 14 18 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. To determine the ubiquitination status of HIV-2 Vpx, and to examine the importance of ubiquitinated Vpx, the 6xHis-tagged Vpx lysine mutants were transfected into 293T cells in conjunction with a plasmid that encodes a Flag-tagged ubiquitin K48R mutant. 2012 Virology Result HIV K48R 241 245 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Ubiquitination of HIV-2 Vpx using K48R ubiquitin mutant. 2012 Virology Result HIV K48R 34 38 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Vpx K84A lacks ubiquitin modification and is similar to Vpx TA. 2012 Virology Result HIV K84A 4 8 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Despite the variation in the P1' conformation, the inhibition is not affected by the mutation as the pyrrolidinone ring maintains interactions with the mutant independent of changes at Pro81' and Val82'/V82A'. 2012 Journal of medicinal chemistry Result HIV V82A 203 207 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Despite these differences, the protease interaction with inhibitor 1 was not disturbed by the N88D mutation. 2012 Journal of medicinal chemistry Result HIV N88D 94 98 PR 31 39 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Effect of conservative mutation of I47V in the catalytic pocket. 2012 Journal of medicinal chemistry Result HIV I47V 35 39 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Effect of V82A mutation on inhibitor P1' conformation. 2012 Journal of medicinal chemistry Result HIV V82A 10 14 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Influence of distal N88D and L76V mutations on the conformation of Asp30. 2012 Journal of medicinal chemistry Result HIV L76V;N88D 29;20 33;24 Asp 67 70 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Interestingly, V82A and N88D mutations have opposite effects on the enzyme activity; PRV82A increases catalytic efficiency and PRN88D decreases catalytic efficiency. 2012 Journal of medicinal chemistry Result HIV N88D;V82A 24;15 28;19 PR;PR 85;127 87;129 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Overall, the inhibitor conformations and protease interactions are not significantly altered by the I47V mutation consistent with essentially identical inhibition of 0.4 nM (Table 2). 2012 Journal of medicinal chemistry Result HIV I47V 100 104 PR 41 49 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Overall, the L76V and N88D mutations appear to disrupt the internal van der Waals contacts and hydrogen bonding network, which may alter the stability of the enzyme with minimal effect on the binding of inhibitors. 2012 Journal of medicinal chemistry Result HIV L76V;N88D 13;22 17;26 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. The contrasting observations are consistent with the location of the V82A mutation in the substrate binding site, while N88D is a distal mutation without direct effect on the substrate. 2012 Journal of medicinal chemistry Result HIV N88D;V82A 120;69 124;73 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. All the PR20 structures show the same large structural change in the flap hinge region (residues 34 to 43) relative to the corresponding wild-type PR structures, which is attributed in part to the E35D, M36I and S37N mutations (Figure 5A). 2012 Biochemistry Result HIV E35D;M36I;S37N 197;203;212 201;207;216 PR;PR 8;147 10;149 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. All three residues are mutated in PR20 where the M36I mutation causes the loop to rearrange so that the shorter Ile36 side chain maintains hydrophobic contacts with mutated I15V and I33F. 2012 Biochemistry Result HIV I15V;I33F;M36I 173;182;49 177;186;53 PR 34 36 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Also, in vitro studies show that combining the two mutations D30N and L90M results in PR that exhibits high levels of resistance to nelfinavir. 2012 Biochemistry Result HIV D30N;L90M 61;70 65;74 PR 86 88 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Also, the hydroxyl side chain of Thr31 forms a new hydrogen bond with the hydroxyl side chain introduced by distal mutation L89T (Figure 5F). 2012 Biochemistry Result HIV L89T 124 128 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Although PR20 and MDR769 exhibit similar twisting of the hinge loop due to the M36I mutation, PR20 bears other mutations in the hinge loop, such as I33F and E35D, that can alter the flexibility of its flaps. 2012 Biochemistry Result HIV E35D;I33F;M36I 157;148;79 161;152;83 PR;PR 9;94 11;96 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Analysis of mutation patterns in eight thousand and sixty virus isolates reveals that N88D is positively associated with D30N, and facilitates the occurrence of major resistance mutations D30N and L90M resulting in multidrug resistance. 2012 Biochemistry Result HIV D30N;D30N;L90M;N88D 121;188;197;86 125;192;201;90 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. By serendipity, the PR20/SQV structure reveals a possible mechanism to prevent the L10F-mediated elimination of the intersubunit ion pair by introducing a large hydrophobic group designed to insert between L10F and Arg8. 2012 Biochemistry Result HIV L10F;L10F 83;206 87;210 PR 20 22 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Comparison of PR20/p2-NCclosed with the corresponding wild type PR/p2-NC structure reveals significant differences as indicated by an RMSD of 1.1 A with the maximum deviation of 4.3 A at the E35D mutation in the hinge loop. 2012 Biochemistry Result HIV E35D 191 195 NC;PR;PR 70;14;64 72;16;66 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. D30N is the only mutation of a charged first shell residue in PR20 and second shell mutation N88D may compensate for the altered charge. 2012 Biochemistry Result HIV N88D;D30N 93;0 97;4 PR 62 64 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. First, mutation of four (D30N, V32I, I47V and I84V) of the seven residues forming the S2/S2' subsites alters their size, shape and charge. 2012 Biochemistry Result HIV D30N;I47V;I84V;V32I 25;37;46;31 29;41;50;35 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Four "first shell" mutations D30N, V32I, I47V and I84V alter residues making direct contacts with DRV and SQV inhibitors. 2012 Biochemistry Result HIV D30N;I47V;I84V;V32I 29;41;50;35 33;45;54;39 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Furthermore, PR20 possesses a network of internal mutations (L10F, I13V, I15V, L33F, M36I, N88D and L89T) that restrain the conformation of residues in the inhibitor binding site. 2012 Biochemistry Result HIV I13V;I15V;L10F;L33F;L89T;M36I;N88D 67;73;61;79;100;85;91 71;77;65;83;104;89;95 PR 13 15 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. However, the central yttrium has no direct or water-mediated interaction with flap residues, although a surface layer of water molecules is visible extending from the catalytic aspartate towards flap residue I54L. 2012 Biochemistry Result HIV I54L 208 212 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. In PR20/DRV, however, the Asn side chain of D30N forms a water mediated hydrogen bond with the major conformation of DRV and introduces a new hydrogen bond with the side chain of the N88D mutation in the second shell (Figure 5B). 2012 Biochemistry Result HIV D30N;N88D 44;183 48;187 PR 3 5 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. In the PR20 structures, the shorter aspartate side chain introduced by the E35D mutation eliminates the ion pair observed between Glu35 and Arg57 at the base of the flap in the wild-type PR, which may affect the monomer stability and increase the variability of PR20 flaps. 2012 Biochemistry Result HIV E35D 75 79 PR;PR;PR 7;187;262 9;189;264 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. In the PR20/SQV complex, the P2' group of SQV shifts more than 1.5 A towards the shorter I84'V to compensate for the larger S2' subsite and maintain interactions with D30N, V32I, I47V and I84V (Figure 5E). 2012 Biochemistry Result HIV D30N;I47V;I84V;V32I 167;179;188;173 171;183;192;177 PR 7 9 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. In the PR20/SQV structure, however, I47V retains the contacts with SQV seen in the PR/SQV. 2012 Biochemistry Result HIV I47V 36 40 PR;PR 7;83 9;85 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. L10F has a critical role in this reorganization, which is consistent with the identification of L10F as an accessory mutation associated with resistance to several PIs. 2012 Biochemistry Result HIV L10F;L10F 96;0 100;4 PI 164 167 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Mutation I47V shows different effects with DRV and SQV. 2012 Biochemistry Result HIV I47V 9 13 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Mutation L10F acts to perturb the intersubunit ion pairs of Arg8-Asp29' and Arg8'-Asp29 at the outer edges of the substrate binding site in the closed forms of PR20. 2012 Biochemistry Result HIV L10F 9 13 Asp;Asp;PR 65;82;160 68;85;162 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Mutation V32I on the opposite side of the S2/S2' subsite restores hydrophobic contact with the side chain of I47V, while showing little effect on interactions with inhibitors. 2012 Biochemistry Result HIV I47V;V32I 109;9 113;13 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Mutations of remote residues like I13V, I15V, M36I and L89T act to accommodate the larger side chains of mutated Phe10 and Phe33 in the hydrophobic core, and coordinate with second and first shell mutations to expand the inhibitor binding site and decrease hydrophobic contacts with inhibitors. 2012 Biochemistry Result HIV I13V;I15V;L89T;M36I 34;40;55;46 38;44;59;50 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Notably, PR20open most closely resembles the free multidrug resistant mutant named MDR769 (1TW7) containing 9 mutations and the inactivating D25N mutation to prevent self-proteolysis, as indicated by the lower RMSD value of 0.61 A for 198 Calpha atoms. 2012 Biochemistry Result HIV D25N 141 145 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Notably, the large aromatic side chain of L33F protrudes into the hydrophobic core of the protein enhancing hydrophobic contacts to distal mutations of I13V, I15V, M36I and second shell residues Ala22 and Ile85 (Figure 5F). 2012 Biochemistry Result HIV I13V;I15V;L33F;M36I 152;158;42;164 156;162;46;168 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. On the other hand, the conformation of the D30N side chain in PR20/SQV resembles that of the PR/SQV complex and lacks a hydrogen bond with N88D. 2012 Biochemistry Result HIV D30N;N88D 43;139 47;143 PR;PR 62;93 64;95 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Similar twisting of the hinge loop is seen in the crystal structures of HIV-1 PRs from subtype B, subtype F and group N that bear the M36I substitution, despite their different space groups and inhibitors. 2012 Biochemistry Result HIV M36I 134 138 PR 78 81 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Similarly, mutations in the active site cavity of PR20 (D30N, V32I, I47V and I84V) alter the charge and increase the distance between the flaps and the base of the cavity relative to the values in MDR769 (V82A and I84V). 2012 Biochemistry Result HIV D30N;I47V;I84V;I84V;V32I;V82A 56;68;77;214;62;205 60;72;81;218;66;210 PR 50 52 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Similarly, the larger L10F side chain adds contacts with Val82 in PR20 (Figure 5C). 2012 Biochemistry Result HIV L10F 22 26 PR 66 68 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Similarly, the previously published HIV-1 protease single mutant complex of M46L/DRV was crystallized at pH 3.6 with no major conformational change relative to PR/DRV . 2012 Biochemistry Result HIV M46L 76 80 PR;PR 42;160 50;162 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Six other mutations Q7K, L10F, L33F, I54L, N88D and L90M are located in the second shell with direct influence on the inhibitor-interacting residues. 2012 Biochemistry Result HIV I54L;L10F;L33F;L90M;N88D;Q7K 37;25;31;52;43;20 41;29;35;56;47;23 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. SQV shows a shorter hydrogen bond of 3.1 A with the carbonyl oxygen of Gly27 compared to a 3.6 A long interaction in the wild type PR, similar to that described recently in the SQV complex with the L76V single mutant. 2012 Biochemistry Result HIV L76V 198 202 PR 131 133 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The D30N single mutant does not form a hydrogen bond with Asn88 and resembles the wild-type structure, while D30N in the D30N, N88D double mutant forms a water mediated hydrogen bond with DRV and a direct hydrogen bond with N88D similar to those in the PR20/DRV complex. 2012 Biochemistry Result HIV D30N;D30N;D30N;N88D;N88D 4;109;121;127;224 8;113;125;131;228 PR 253 255 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The flaps in MDR769 retain intersubunit contacts; the side chains of Ile50/50' at the tip of both flaps have van der Waals contacts with Pro81'/81 from the opposite monomer, despite the presence of D25N that by itself increases the Kd of wild type PR by two orders of magnitude. 2012 Biochemistry Result HIV D25N 198 202 PR 248 250 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The hydrophobic contacts of Val82 and Ile85 with L10F and L33F may contribute to the decreased interactions of the 80's loop with inhibitor and the flaps observed in PR20 complexes. 2012 Biochemistry Result HIV L10F;L33F 49;58 53;62 PR 166 168 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The I84V mutation in PR20/SQV eliminates hydrophobic contacts with the P1' and P1 groups of SQV, similar to the effects of I84V in PR20/DRV and in the single I84V mutant complex. 2012 Biochemistry Result HIV I84V;I84V;I84V 4;123;158 8;127;162 PR;PR 21;131 23;133 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The interactions formed by second shell residues Thr31 and L33F and 6 distal mutations maintain the main chain of residues 30-32 further from the inhibitor as shown by ~1 A increased separation between the Calpha atoms of residues 32 and 50 in the PR20 inhibitor complexes compared to the equivalent wild type structures. 2012 Biochemistry Result HIV L33F 59 63 PR 248 250 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The L90M single mutation significantly reduces the dimer stability of PR and increases the catalytic activity. 2012 Biochemistry Result HIV L90M 4 8 PR 70 72 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The major conformation of the Arg8 side chain rotates to form multiple van der Waals contacts with the edge of the aromatic Phe side chain of L10F, which abolishes the ion pair with Asp29' and the hydrophobic contacts with DRV (Figure 5C). 2012 Biochemistry Result HIV L10F 142 146 Asp 182 185 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The minor conformation of DRV exhibits a direct hydrogen bond to D30N and no hydrogen bond forms between the side chains of D30N and N88D. 2012 Biochemistry Result HIV D30N;D30N;N88D 65;124;133 69;128;137 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. The second shell mutation of L90M exhibits a similar effect in PR20 and single mutant structures. 2012 Biochemistry Result HIV L90M 29 33 PR 63 65 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. These short interactions of L90M disturb the active site at the dimer interface and may contribute to the increased dimer dissociation observed for PR20 relative to PR. 2012 Biochemistry Result HIV L90M 28 32 PR;PR 148;165 150;167 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. This inhibitor independent mechanism may explain why L90M has been identified as a resistance mutation for all clinical inhibitors except for DRV and TPV. 2012 Biochemistry Result HIV L90M 53 57 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. This rearrangement is in agreement with the molecular dynamics studies that predict increased flexibility of the flaps due to E35D and M36I mutations. 2012 Biochemistry Result HIV E35D;M36I 126;135 130;139 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. This rotation of Arg8 away from Asp29' is prevented in the PR20/SQV complex, since the P2 group of SQV-2 bound at the second site inserts between the side chains of Arg8 and L10F mutation (Figure 5D). 2012 Biochemistry Result HIV L10F 174 178 Asp;PR 32;59 35;61 22404139 HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements. Variations in the interaction of D30N with DRV and N88D were reported for a DRV-resistant clinical isolate. 2012 Biochemistry Result HIV D30N;N88D 33;51 37;55 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. Eleven of the 18 patients in the M41L cluster were part of the present study and seven belonged to the 1992-2002 dataset. 2012 PloS one Result HIV M41L 33 37 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. Multidrug resistance (MDR) involving all three drug as well as the Q151M complex was observed in five patients (patients 57-61). 2012 PloS one Result HIV Q151M 67 72 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. The first patient in the M41L cluster was diagnosed in 1994. 2012 PloS one Result HIV M41L 25 29 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. The largest TDR cluster (cluster 4) consisted of 18 MSM from Stockholm with viruses that had the M41L resistance mutation (Figure 1). 2012 PloS one Result HIV M41L 97 101 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. The M41L mutation represented almost half (16 of 34) of the NRTI-related singleton mutations and the K103N mutation represented two-thirds (10 of 15) of the NNRTI-related singleton mutations. 2012 PloS one Result HIV K103N;M41L 101;4 106;8 NNRTI;NRTI 157;60 162;64 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. This includes two patients diagnosed in 2010, which shows that the M41L variant has been circulating in Stockholm between 1994 and 2010. 2012 PloS one Result HIV M41L 67 71 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. Two of the M41L viruses had additional mutations (T215N and M46LM, respectively). 2012 PloS one Result HIV M41L;M46L;M46M;T215N 11;60;60;50 15;65;65;56 22485165 BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region. In the subtype B samples, V151I was also the most frequent change in 23.3% of the patients. 2012 PloS one Result HIV V151I 26 31 22485165 BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region. Interestingly, unlike the F and BF samples, S230N was the second most common mutation, present in 8.5% of the subtype B sequences. 2012 PloS one Result HIV S230N 44 49 22485165 BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region. Likewise, V151I (25%) was the most common minor resistance mutation among the BF recombinant integrases, which also had 1 sample sporting M154I. 2012 PloS one Result HIV M154I;V151I 138;10 143;15 IN 93 103 22485165 BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region. Other B resistance-associated mutations were L74M (0.8%), T97A (1.6%), E138K (0.8%), M154I (3.9%), M154L (0.8%), E157K (2.3%), G163R (3.1%), and I203M (3.1%). 2012 PloS one Result HIV E138K;E157K;G163R;I203M;L74M;M154I;M154L;T97A 71;113;127;145;45;85;99;58 76;118;132;150;49;90;104;62 22485165 BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region. The polymorphisms E138D, M154I, and S230N were also found in 1 sample each. 2012 PloS one Result HIV E138D;M154I;S230N 18;25;36 23;30;41 22485165 BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region. V151I was the most frequent and found to be present in 65.2% (5/8) of the cases. 2012 PloS one Result HIV V151I 0 5 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. Finally, the capacity of the different backbone phenotyping to predict ARV drug resistance associated with the M184V, K103N and V106M mutations was assessed. 2012 PloS one Result HIV K103N;M184V;V106M 118;111;128 123;116;133 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. Table 3 summarizes ROC curve analyses, which demonstrates the tradeoff between sensitivity and specificity for the subtype B- and C- backbone based phenotyping assays in detecting decreased sensitivity caused by M184V, K103N and V106M mutations. 2012 PloS one Result HIV K103N;M184V;V106M 219;212;229 224;217;234 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. The most prevalent mutations in this dataset included: K103N (n = 30; 38.5%), M184V (n = 26; 33.3%), T215Y (n = 13; 16.7%), T215F (n = 8; 10.3%), M41L (n = 9; 11.5%), V106M (n = 8; 10.3%), D67N (n = 9; 11.5%), V108I (n = 8; 10.3%). 2012 PloS one Result HIV D67N;K103N;M184V;M41L;T215F;T215Y;V106M;V108I 189;55;78;146;124;101;167;210 193;60;83;150;129;106;172;215 22496972 Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India. Accessory minor PI mutations K20R, M36I, and H69K were seen in 7.3% (5/68), 97% (66/68), and 49% (33/68) patients, respectively; L63P, A71E, A71V, I13V, L10V, K45I, and K45R were observed in one patient each. 2012 AIDS research and treatment Result HIV A71E;A71V;H69K;I13V;K20R;K45I;K45R;L10V;L63P;M36I 135;141;45;147;29;159;169;153;129;35 139;145;49;151;33;163;173;157;133;39 PI 16 18 22496972 Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India. One patient (1.47%) had RT mutation, M184V that imparts resistance to NRTIs, lamivudine, and emtricitabine, and another (1.47%) had a major PI mutation, D30N, conferring resistance to nelfinavir. 2012 AIDS research and treatment Result HIV D30N;M184V 153;37 157;42 NRTI;PI;RT 70;140;24 75;142;26 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. 1H-15 N HSQC NMR experiments were performed to assess the effects of the E45A, P38A, E45A/R132T and R132T mutations on the structure of the N-terminal domain of CA (CA-NTD). 2012 Retrovirology Result HIV E45A;E45A;P38A;R132T;R132T 73;85;79;90;100 77;89;83;95;105 Capsid;Capsid 161;165 163;167 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Accordingly, the P38A substitution destabilized the viral capsid, while E45A resulted in a hyperstable capsid. 2012 Retrovirology Result HIV E45A;P38A 72;17 76;21 Capsid;Capsid 58;103 64;109 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Addition of the R132T substitution restores sensitivity of the E45A mutant to the small molecule inhibitor PF74. 2012 Retrovirology Result HIV E45A;R132T 63;16 67;21 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. As previously shown, the E45A mutant virus exhibited strong resistance to PF74 (Figure 8). 2012 Retrovirology Result HIV E45A 25 29 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. By contrast, P38A mutant particles were approximately 80% less effective at abrogating restriction, as we previously reported. 2012 Retrovirology Result HIV P38A 13 17 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. By contrast, the E45A/R132T mutant exhibited nearly wild type sensitivity (IC50 = 0.38 muM vs. 2012 Retrovirology Result HIV E45A;R132T 17;22 21;27 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Collectively, these results indicate that the suppressor mutations do not correct the aberrant intrinsic stability of the P38A and E45A mutant capsids observed in vitro. 2012 Retrovirology Result HIV E45A;P38A 131;122 135;126 Capsid 143 150 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Collectively, these results suggest that the T216I mutation prevents premature disassembly of the P38A mutant core in target cells, thereby relieving the impaired ability of the mutant core to interact with restriction factors. 2012 Retrovirology Result HIV P38A;T216I 98;45 102;50 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Contrary to our expectation, cores recovered from the double mutants P38A/T216I and E45A/R132T exhibited CA levels that were similar to those of the corresponding single mutants (Figure 4A and 4B). 2012 Retrovirology Result HIV E45A;P38A;R132T;T216I 84;69;89;74 88;73;94;79 Capsid 105 107 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. control cells, while the wild type and E45A/R132T double mutant were only slightly (less than 50%) reduced in arrested cells. 2012 Retrovirology Result HIV E45A;R132T 39;44 43;49 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Cores isolated from E45A and E45A/R132T both exhibited slower uncoating in vitro relative to wild-type cores (Figure 4C). 2012 Retrovirology Result HIV E45A;E45A;R132T 20;29;34 24;33;39 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. E45A) were competent in the assay. 2012 Retrovirology Result HIV E45A 0 4 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. For example, in the E45A mutant only Gly46 (except the mutated residue Glu45) exhibited a large (~ 0.8 ppm) chemical shift change. 2012 Retrovirology Result HIV E45A 20 24 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. For P38A/T216I mutant particles, the activity was intermediate between wild type and P38A levels. 2012 Retrovirology Result HIV P38A;P38A;T216I 4;85;9 8;89;14 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. However, the accelerated rate of assembly of E45A was not affected by the suppressor mutation R132T. 2012 Retrovirology Result HIV E45A;R132T 45;94 49;99 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Importantly, the T216I mutation partially rescued the impaired reverse transcription exhibited by P38A (Figure 3), consistent with the interpretation that the impaired infectivity exhibited by P38A is owing to its reduced reverse transcription capacity. 2012 Retrovirology Result HIV P38A;P38A;T216I 98;193;17 102;197;22 RT;RT 63;222 84;243 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In both cell lines, the T216I single mutant exhibited a similar level of activity as the wild type, demonstrating that the rescue of the P38A mutant activity was not due to a general enhancement of activity by the suppressor mutation. 2012 Retrovirology Result HIV P38A;T216I 137;24 141;29 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In contrast to the original P38A and E45A mutants, which failed to replicate in CEM cells within 26 days, the P38A/T216I and E45A/R132T double mutants both replicated, though each was delayed relative to the wild type (Figure 1A, B). 2012 Retrovirology Result HIV E45A;E45A;P38A;P38A;R132T;T216I 37;125;28;110;130;115 41;129;32;114;135;120 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In contrast, the E45A mutant assembled within 2 minutes (Figure 5A). 2012 Retrovirology Result HIV E45A 17 21 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In contrast, the P38A and P38A/T216I mutants behaved similar to wild type HIV-1 and were only slightly less infectious for arrested vs. 2012 Retrovirology Result HIV P38A;P38A;T216I 17;26;31 21;30;36 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In contrast, the recovery of CA in P38A cores was about 2%, while that for E45A cores was approximately 20% (Figure 4B). 2012 Retrovirology Result HIV E45A;P38A 75;35 79;39 Capsid 29 31 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In contrast, the spectrum of the P38A mutant exhibited overall smaller changes (< 0.42 ppm), but the mutation affected more residues that were dispersed over a wider region. 2012 Retrovirology Result HIV P38A 33 37 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In follow-up studies, we have repeatedly observed that the E45A mutation does not impair reverse transcription, but results in impairment at later stages of infection, after nuclear entry (Figure 3). 2012 Retrovirology Result HIV E45A 59 63 RT 89 110 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In previous studies, we observed that the P38A mutation impairs the ability of HIV-1 particles to abrogate host restriction in simian cells owing to capsid instability. 2012 Retrovirology Result HIV P38A 42 46 Capsid 149 155 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In rhesus macaque cells, in which HIV-1 infection is restricted by TRIM5alpha, the impaired abrogation activity of P38A mutant particles was also rescued by the T216I suppressor mutation (Figure 9B). 2012 Retrovirology Result HIV P38A;T216I 115;161 119;166 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In this respect, E45A resembles the Q63A/Q67A CA mutant, which exhibits delayed uncoating in target cells and is impaired for nuclear import and integration. 2012 Retrovirology Result HIV E45A;Q63A;Q67A 17;36;41 21;40;45 Capsid 46 48 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Infection by the E45A mutant was reduced by eight-fold in arrested vs. 2012 Retrovirology Result HIV E45A 17 21 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Our group previously showed that the P38A and E45A mutant capsids exhibited altered stability without major structural defects, and were impaired for reverse transcription, suggesting that the mutations result in aberrant uncoating in target cells. 2012 Retrovirology Result HIV E45A;P38A 46;37 50;41 RT;Capsid 150;58 171;65 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Our group previously showed that the P38A and E45A mutants are impaired at an early post-entry stage of infection. 2012 Retrovirology Result HIV E45A;P38A 46;37 50;41 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Purified recombinant CA proteins encoding the E45A and E45A/R132T mutations were diluted into a high salt buffer, and the turbidity of the solution was monitored spectrophotometrically for 15 minutes following initiation of the reactions. 2012 Retrovirology Result HIV E45A;E45A;R132T 46;55;60 50;59;65 Capsid 21 23 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Quantitation of virus infectivity using the HeLa-P4 cell line (HeLa-CD4/LTR-lacZ) revealed that the T216I and R132T second-site mutations markedly enhanced the infectivity of P38A and E45A, respectively (Figure 2). 2012 Retrovirology Result HIV E45A;P38A;R132T;T216I 184;175;110;100 188;179;115;105 LTR 72 75 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Reasoning that the hyperstability of the E45A viral capsid may be related to the accelerated CA assembly kinetics in vitro, we asked whether the suppressor mutations would affect the rate of CA assembly. 2012 Retrovirology Result HIV E45A 41 45 Capsid;Capsid;Capsid 52;93;191 58;95;193 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Resonance changes caused by the E45A and R132T mutations when compared with the wild type spectrum were essentially confined to the mutation sites. 2012 Retrovirology Result HIV E45A;R132T 32;41 36;46 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Second-site suppressor mutations enhance the infectivity of the P38A and E45A mutants in a single-cycle assay. 2012 Retrovirology Result HIV E45A;P38A 73;64 77;68 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Second-site suppressor mutations restore replication to the P38A and E45A mutants. 2012 Retrovirology Result HIV E45A;P38A 69;60 73;64 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Sequence analysis of PCR products from the E45A culture revealed the presence of a mutation at codon 132 resulting in a substitution of Arg to Thr (R132T) in addition to the original E45A mutation. 2012 Retrovirology Result HIV E45A;E45A;R132T 43;183;148 47;187;153 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Sequence analysis of PCR products from the P38A culture revealed the presence of a mutation at codon 216 resulting in a substitution of Thr to Ile (T216I) in addition to the original P38A mutation. 2012 Retrovirology Result HIV P38A;P38A;T216I 43;183;148 47;187;153 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Several mutations in CA, including E45A, result in selective impairment of infection of mitotically-arrested cells. 2012 Retrovirology Result HIV E45A 35 39 Capsid 21 23 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Similarly, only neighboring residues (Ile129, Trp133, and Leu136) were associated with noticeable changes, ranging from 0.3 to 1 ppm in the R132T mutant. 2012 Retrovirology Result HIV R132T 140 145 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Superpositions of the 1H-15 N HSQC spectra of wild-type and E45A (A), P38A (B), E45A/R132T (C) and R132T (D) mutants are shown in Additional file 1. 2012 Retrovirology Result HIV E45A;E45A;P38A;R132T;R132T 60;80;70;85;99 64;84;74;90;104 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The E45A mutation was previously reported to accelerate HIV-1 CA assembly in vitro, suggesting that this mutation enhances protein-protein interactions between CA subunits. 2012 Retrovirology Result HIV E45A 4 8 Capsid;Capsid 62;160 64;162 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The E45A substitution rendered HIV-1 resistant to PF74, presumably by stabilizing the capsid, as the mutation did not reduce PF74 binding to mature HIV-1 particles. 2012 Retrovirology Result HIV E45A 4 8 Capsid 86 92 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The P38A and P38A/T216I mutant proteins also exhibited accelerated assembly, reaching completion within 3-4 minutes (Figure 5B). 2012 Retrovirology Result HIV P38A;P38A;T216I 4;13;18 8;17;23 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The poor recovery of core-associated CA from the P38A mutant particles precluded its analysis. 2012 Retrovirology Result HIV P38A 49 53 Capsid 37 39 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The R132T mutation relieves the cell-cycle dependence of the E45A mutant. 2012 Retrovirology Result HIV E45A;R132T 61;4 65;9 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The restored sensitivity of the double mutant virus to PF74 suggests that the R132T mutation partially reverses the E45A-induced uncoating defect in target cells. 2012 Retrovirology Result HIV E45A;R132T 116;78 120;83 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The small, but more widespread effects of the P38A mutation on the protein structure suggest that modulation of structural properties occurs in the mutant. 2012 Retrovirology Result HIV P38A 46 50 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The T216I mutation restores the ability of P38A particles to saturate TRIM5 host restrictions in monkey cells. 2012 Retrovirology Result HIV P38A;T216I 43;4 47;9 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The T216I mutations partially relieves the reverse transcription impairment exhibited by P38A. 2012 Retrovirology Result HIV P38A;T216I 89;4 93;9 RT 43 64 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Therefore, we sought to determine whether the second-site mutations rescue the P38A and E45A mutant viruses in a single-round reporter assay. 2012 Retrovirology Result HIV E45A;P38A 88;79 92;83 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. These results demonstrate that the respective second-site mutations, T216I and R132T, partially restore the ability of the corresponding P38A and E45A mutant viruses to replicate in CEM cells. 2012 Retrovirology Result HIV E45A;P38A;R132T;T216I 146;137;79;69 150;141;84;74 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. These results indicate that the R132T mutation corrects the selective impairment of infection of nondividing cells associated with the E45A mutant virus. 2012 Retrovirology Result HIV E45A;R132T 135;32 139;37 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Thus, the effects of the E45A and P38A mutations on CA assembly in vitro were not correlated with the biological phenotypes of the corresponding CA mutant viruses. 2012 Retrovirology Result HIV E45A;P38A 25;34 29;38 Capsid;Capsid 52;145 54;147 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Thus, the R132T second-site substitution rescued the impaired ability of E45A infection in nondividing cells. 2012 Retrovirology Result HIV E45A;R132T 73;10 77;15 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. To determine whether these second-site substitutions were responsible for the accelerated growth kinetics of the adapted viruses, the mutations were transferred into the original P38A and E45A mutant viral clones. 2012 Retrovirology Result HIV E45A;P38A 188;179 192;183 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. To further evaluate the relative stability of E45A mutant HIV-1 cores, we assayed the rate of CA dissociation from purified cores in vitro. 2012 Retrovirology Result HIV E45A 46 50 Capsid 94 96 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. To further probe the effects of the suppressor mutation R132T on the phenotype of the E45A mutant in target cells, we compared the sensitivity of wild type, E45A, and E45A/R132T mutant viruses to inhibition by PF74 in single-cycle infection assays. 2012 Retrovirology Result HIV E45A;E45A;E45A;R132T;R132T 86;157;167;56;172 90;161;171;61;177 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. To probe the role of domain interactions in maintaining optimal HIV-1 capsid stability, second-site suppressor mutations were isolated by serial passage of P38A and E45A mutant viruses in human CEM T cells. 2012 Retrovirology Result HIV E45A;P38A 165;156 169;160 Capsid 70 76 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. To test whether the second-site suppressor restores capsid stability in target cells, we asked whether T216I restores the ability of P38A particles to abrogate restriction. 2012 Retrovirology Result HIV P38A;T216I 133;103 137;108 Capsid 52 58 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. We also constructed and determined the infectivity of the single mutants T216I and R132T. 2012 Retrovirology Result HIV R132T;T216I 83;73 88;78 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. We conclude that the E45A and R132T mutations induce highly localized structural changes, indicating that the effects of the mutations simply result from the change in chemical nature of the substituted amino acid. 2012 Retrovirology Result HIV E45A;R132T 21;30 25;35 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. We therefore asked whether introduction of the R132T mutation in the E45A mutant virus CA would relieve its cell-cycle-dependence in arrested HeLa cells. 2012 Retrovirology Result HIV E45A;R132T 69;47 73;52 Capsid 87 89 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. 23 nM) that reflected the influence of the F519I change (Figs.1,2 and Table 2). 2012 Virology Result HIV F519I 43 48 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. A transient replacement of Ala by Ser at position 533 of gp41 during passage 4 (indicated by X in Fig.5B) coincided temporally with an increase in MPI from 79% to 86% between passages 3 and 4. 2012 Virology Result HIV A533S 27 53 gp41 57 61 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Although all three FP changes are required for complete VCV-resistance, two double mutants, S+a,b and S+a,c (changes G516V+M518V and G516V+F519I, respectively), were partially resistant (Fig.1B). 2012 Virology Result HIV F519I;G516V;G516V;M518V 139;117;133;123 144;122;138;128 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Among the three FP changes, F519I caused the biggest leftward shift of the dose-response curve, and thus the greatest reduction in IC50 (1.4 nM for S+c vs. 2012 Virology Result HIV F519I 28 33 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. As before, the G516V change in the S+a mutant caused a leftward shift of the inhibition curve and a consequent IC50 reduction compared to S (4.6 nM vs. 2012 Virology Result HIV G516V 15 20 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. At low concentrations (~0.3-2 nM), the third substitution, F519I, confers an increase in VCV sensitivity; thus under these conditions, S+a,c is more sensitive than S+a,b (IC50 0.20 vs. 2012 Virology Result HIV F519I 59 64 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. By itself, the T244A change modestly (~2 fold) reduced the IC50 for VCV when introduced into clone S (0.50 nM vs. 2012 Virology Result HIV T244A 15 20 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Effects of the T244A change on resistance of FP mutants. 2012 Virology Result HIV T244A 15 20 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. From here on, we refer to the G516V, M518V and F519I changes as a, b and c, respectively (see Table 1 for virus nomenclature). 2012 Virology Result HIV F519I;G516V;M518V 47;30;37 52;35;42 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Here, however, they were accompanied by a gp120-C2 substitution, T244A, that appears to counter the VCV-resistance phenotype created by the FP substitutions. 2012 Virology Result HIV T244A 65 70 gp120 42 47 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. In particular, three different passage 9 clones contained one of the V3 substitutions T303A, F515L or T317A in addition to the three FP changes (data not shown). 2012 Virology Result HIV F515L;T303A;T317A 93;86;102 98;91;107 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. In the TZM-bl cell assay, the inhibition curve for S+a,b,c+T244A was shifted to the right and slightly upward compared to S+a,b,c, yielding increased IC50 and MPI values (1.5 nM vs. 2012 Virology Result HIV T244A 59 64 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. On both cell types, the greatest differences in Kdi compared to the S virus were seen with S+c and all the other mutants containing the F519I change (i.e., mutation-c). 2012 Virology Result HIV F519I 136 141 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Once it emerged, the T244A substitution persisted together with the 3FP changes. 2012 Virology Result HIV T244A 21 26 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Overall, the G516V change appears to play the most important role in VCV-resistance; when it is accompanied by either of the M518V or F519I substitutions, the resulting virus is significantly, but incompletely, resistant. 2012 Virology Result HIV F519I;G516V;M518V 134;13;125 139;18;130 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The F519I change caused the most pronounced leftward shift in the dose-response curves in both PBMC and TZM-bl cells, and consequently the greatest IC50 reductions (Figs.1,2). 2012 Virology Result HIV F519I 4 9 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The F519I substitution causes a more pronounced leftward shift and a further reduction in the IC50 value (0.13 nM vs. 2012 Virology Result HIV F519I 4 9 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The G516V change also causes a leftward shift of the dose-response curve and, thus, a slight reduction in IC50 compared to the sensitive, virus S (0.31 nM vs. 2012 Virology Result HIV G516V 4 9 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The genetic routes to VCV resistance may involve solely V3 changes [as in isolate CC101.19, ]; solely FP changes [as in isolate D1/85.16, ]; or a combination of substitutions in gp41 acting in concert with at least the H308P change in V3 [as in resistant viruses from the D101.12 lineage, ]. 2012 Virology Result HIV H308P 219 224 gp41 178 182 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The inhibition curve for the S+b mutant (M518V substitution) completely coincided with that of the sensitive virus S. 2012 Virology Result HIV M518V 41 47 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The inhibition curves for S+a,b,c+T244A and S+a,b,c were both still shifted to the left compared to S (IC50 values 0.18 nM and 0.24 nM vs. 2012 Virology Result HIV T244A 34 39 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The M518V (i.e., mutation-b) and F519I changes can both synergize with G516V to confer the ability to use VCV-CCR5 complexes. 2012 Virology Result HIV F519I;G516V;M518V 33;71;4 38;76;9 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The most influential resistance-associated change in the FP, mutation-a, had reverted to the cognate amino acid residue (V516G) in 1/12 passage 5 clones, R.r5 cl.11, but all 11 clones from virus R.r9 retained the three FP substitutions. 2012 Virology Result HIV V516G 121 126 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The S+a,b,c mutant was little affected by the T244A change, with both viruses replicating in the 103-104 TCID50/mL range. 2012 Virology Result HIV T244A 46 51 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The S+a,b,c+T244A mutant was VCV-sensitive in a PBMC-based multi-cycle assay. 2012 Virology Result HIV T244A 12 17 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The S+b,c virus is VCV-sensitive but its IC50 was reduced to 0.17 nM, presumably due to the impact of the F519I change. 2012 Virology Result HIV F519I 106 111 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The T244A mutation reduced the PBMC titers of the parental clone S by several-fold (103-104 compared to 104-105 TCID50/mL). 2012 Virology Result HIV T244A 4 9 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. This change, M518V, has little or no effect on VCV sensitivity on its own and appears to be under no pressure to revert. 2012 Virology Result HIV M518V 13 18 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Thus, 2/10 clones from passage 4, 11/12 clones from passage 5 and all 11 clones from passage 9 contained the T244A change (Fig.5A). 2012 Virology Result HIV T244A 109 114 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Thus, the G516V change (i.e., mutation-a) is a crucial but insufficient contributor to the usage of VCV-CCR5 complexes (Fig.3A); the F519I mutation (i.e., mutation-c) is an independent determinant of preference for the unoccupied high-affinity form of CCR5 (Fig.3B). 2012 Virology Result HIV F519I;G516V 133;10 138;15 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Thus, whereas the VCV-inhibition curve for S+a,b,c has a complex shape, the one for S+a,b,c+T244A resembles the parental clone S (Fig.7A). 2012 Virology Result HIV T244A 92 97 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. To study the T244A substitution, we introduced it into the VCV-sensitive clone S and the resistant triple mutant S+a,b,c and tested the resulting replication-competent viruses for VCV sensitivity in PBMC and TZM-bl cells. 2012 Virology Result HIV T244A 13 18 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Two new gp41 mutations V703A and W755R, located in the transmembrane region and the cytoplasmic tail, appeared during passage 4 but they were sustained only for one and two more passages, respectively (Fig.5D). 2012 Virology Result HIV V703A;W755R 23;33 28;38 gp41 8 12 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. We conclude that M518V and F519I complement the G516V substitution in qualitatively distinct ways, but together the three changes largely recreate the VCV-resistance phenotype of the reference virus, R. 2012 Virology Result HIV F519I;G516V;M518V 27;48;17 32;53;22 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. We describe below studies on the phenotype conferred by the T244A substitution. 2012 Virology Result HIV T244A 60 65 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. We have shown that the VCV-resistant phenotypes of the HIV-1 R5 primary isolate D1/85.16, and viruses derived from it, were attributable to three conservative sequence changes (G516V, M518V and F519I) in the gp41 FP. 2012 Virology Result HIV F519I;G516V;M518V 194;177;184 199;182;189 gp41 208 212 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. When M518V is added to the other two changes, it has an incremental effect on the capacity to use VCV-CCR5 complexes on PBMC. 2012 Virology Result HIV M518V 5 10 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. When the PBMC inhibition curves for the single FP mutants were analyzed in more detail, it was apparent that the G516V change does confer very low resistance to the S+a mutant, as manifested by the marginal (~3%) level of replication (MPI = 97%) that can be detected at high VCV concentrations (up to 5 microM). 2012 Virology Result HIV G516V 113 118 22530020 Counteraction of tetherin antiviral activity by two closely related SIVs differing by the presence of a Vpu gene. As shown on figure 5 A and B, neither of the P40L or T45I substitutions alone were able to alter the strong specificity of HIV-1 Vpu for human tetherin, even if the P40L mutation significantly increased susceptibility of human tetherin to SIVden Vpu. 2012 PloS one Result HIV P40L;P40L;T45I 45;165;53 49;169;57 Vpu;Vpu 129;246 132;249 22530020 Counteraction of tetherin antiviral activity by two closely related SIVs differing by the presence of a Vpu gene. When both P40L and T45I were expressed together in human tetherin, however, susceptibility of this mutant protein to HIV-1 Vpu dropped sharply, while susceptibility to SIVden Vpu increased to 50%, a level close to that observed with wild-type C. 2012 PloS one Result HIV P40L;T45I 10;19 14;23 Vpu;Vpu 123;175 126;178 22534017 Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation. Therefore, we used the wild-type 5C Nef, a primary Nef previously characterized as a strong activator of Pak2, and two well-characterized 5C-mutants that have wild-type abilities to downregulate CD4 but are defective for the ability to associate with and activate Pak2: 5C-7 (F85L, F89H, H191F in NL4-3) and 5C-AxxA (A72P, A75P). 2012 Retrovirology Result HIV A72P;A75P;F85L;F89H;H191F 317;323;276;282;288 321;327;280;286;293 Nef;Nef 36;51 39;54 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. As for different mutation patterns including K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C and K103N, H221Y conferred NVP IC50 increased folds 2.2 +- 0.9, 3.2 +- 0.3, 3.6 +- 0.5, 3.0 +- 0.4, 2.1 +- 0.5, and 2.2 +- 0.1, respectively (Table 2). 2012 AIDS research and treatment Result HIV H221Y;K101Q;K101Q;K103N;K103N;V179D;V179D;Y181C;Y181C;Y181C 108;45;58;85;101;65;78;51;71;91 113;50;63;90;106;70;83;56;76;96 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Association of H221Y with an Increased NVP IC50 Based on Various Mutation Profiles. 2012 AIDS research and treatment Result HIV H221Y 15 20 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Association of Y181C with an Increased NVP IC50 Based on Various Mutation Profiles. 2012 AIDS research and treatment Result HIV Y181C 15 20 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Association of Y181C/H221Y with an Increased NVP IC50 Based on Various Mutation Profiles. 2012 AIDS research and treatment Result HIV H221Y;Y181C 21;15 26;20 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Compared to pNL4-3, the resistance values (folds of IC50 increased) derived from viruses carrying different mutation profiles such as K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, K101Q, V179D/Y181C/H221Y, V179D/Y181C, V179D/H221Y, V179D, K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y, and K103N were 3740.8 +- 314.1, 1490.9 +- 354.4, 4.4 +- 1.2, 1.2 +- 0.2, 5090.6 +- 744.6, 1413.0 +- 269.8, 13.4 +- 1.9, 4.6 +- 1.3, 5859.3 +- 1648.2, 2802.4 +- 124.1, 139.2 +- 8.2, and 63.8 +- 3.1 folds, respectively (Table 1). 2012 AIDS research and treatment Result HIV H221Y;H221Y;H221Y;K101Q;K103N;V179D;Y181C;Y181C;Y181C;H221Y;H221Y;H221Y;K101Q;K101Q;K101Q;K103N;K103N;K103N;V179D;V179D;V179D;Y181C;Y181C;Y181C 146;198;250;134;238;186;140;192;244;172;224;276;153;166;179;257;270;287;205;218;231;159;211;263 151;203;255;139;243;191;145;197;249;177;229;281;158;171;184;262;275;292;210;223;236;164;216;268 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Concerning K101Q, V179D, and K103N, Y181C/H221Y mutation combination improved the IC50s of NVP 3444.6 +- 834.5, 1132.6 +- 180.4, and 100.6 +- 32.5 folds, respectively (Table 2). 2012 AIDS research and treatment Result HIV H221Y;K101Q;K103N;V179D;Y181C 42;11;29;18;36 47;16;34;23;41 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. In relation to various mutation profiles such as K101Q/H221Y, K101Q, V179D/H221Y, V179D, K103N/H221Y, and K103N, Y181C mutation increased folds of NVP and IC50s were 759.1 +- 41.9, 1297.0 +- 289.1, 390.0 +- 101.6, 312.5 +- 45.3, 41.9 +- 8.4, and 47.9 +- 4.2, respectively (Table 2). 2012 AIDS research and treatment Result HIV H221Y;H221Y;H221Y;K101Q;K101Q;K103N;K103N;V179D;V179D;Y181C 55;75;95;49;62;89;106;69;82;113 60;80;100;54;67;94;111;74;87;118 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. These viruses were named 101Q-1, 101Q-2, 101Q-3, 101Q-4, 179D-1, 179D-2, 179D-3, 179D-4, 103N-1, 103N-2, 103N-3, and 103N-4; the mutation patterns they contained were K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, K101Q, V179D/Y181C/H221Y, V179D/Y181C, V179D/H221Y, V179D, K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y, and K103N. 2012 AIDS research and treatment Result HIV H221Y;H221Y;H221Y;K101Q;K103N;V179D;Y181C;Y181C;Y181C;H221Y;H221Y;H221Y;K101Q;K101Q;K101Q;K103N;K103N;K103N;V179D;V179D;V179D;Y181C;Y181C;Y181C 179;231;283;167;271;219;173;225;277;205;257;309;186;199;212;290;303;320;238;251;264;192;244;296 184;236;288;172;276;224;178;230;282;210;262;314;191;204;217;295;308;325;243;256;269;197;249;301 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Overall, the prevalence of SNP mutations in dhfr 51, 59, 108 and dhps 437, 540 differed significantly among the three studies (P < 0.031), noticeably increasing from 78.9 % to 97.7 % (N51I), 51.7 % to 90.2 % (C59R), 97.8 % to 100 % (S108N), 42.8 % to 100 % (A437G) and 31.1 % to 99.2 % (K540E), respectively from 1996-2000 to 2008-2009 (Table 1). 2012 Malaria journal Result HIV A437G;C59R;K540E;N51I;S108N 258;209;287;184;233 263;213;292;188;238 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. The prevalence of dhps 436 mutations including S436A, S436F, and S436H was 11.7 %, 2.8 % and 6.1 % for the three studies, respectively, among which the new 436 mutation, S436H, was detected in 2.3 % of 2002-2008 and 3.8 % of 2008-2009 samples. 2012 Malaria journal Result HIV S436A;S436F;S436H;S436H 47;54;65;170 52;59;70;175 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. The prevalence of the dhfr triple mutant (N51I/C59R/S108N) increased considerably from 27 % in 1996-2000 to 89 % in 2008-2009 and was significantly different across studies (P < 0.001), while the dhps double mutant (A437G/K540E) also increased from 27 % to 99 % and also differed significantly among studies (P < 0.001) [Figure 2A, B, respectively]. 2012 Malaria journal Result HIV C59R;N51I;S108N;A437G;K540E 47;42;52;216;222 51;46;57;221;227 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. About 30% of all sequences have an Arg residue at position G335; and given that the G355R mutant does not impact on the miniCD4's affinity, this mutant was excluded from further analysis. 2012 Retrovirology Result HIV G355R 84 89 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. All mutant S375R pseudoviruses had a dramatic increase in IC50 for the miniCD4 M48U1 compared to wild type pseudovirus IC50 values (Figure 2C). 2012 Retrovirology Result HIV S375R 11 16 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Also the L494V mutant, although more conserved, but located away from the miniCD4 interaction site and not affecting CD4 binding, was excluded. 2012 Retrovirology Result HIV L494V 9 14 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Although a third of the known gp120 sequences share an Asn474 residue, it was the only mutation found to be associated with M48 resistance in SF162, and therefore it was tested alongside the H105Y, V255M, S375R/N and G471R mutants. 2012 Retrovirology Result HIV G471R;H105Y;S375N;S375R;V255M 217;191;205;205;198 222;196;212;212;203 gp120 30 35 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Because the infectivity of the V255M substitution was dramatically reduced, no IC50 could be calculated. 2012 Retrovirology Result HIV V255M 31 36 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Both G335 and G471 were mutated into an arginine in rM48U1SF162_a after the S375R mutation was induced, whereas V255M and L494V mutations were observed in rM48U1SF162_b prior to the appearance of S375N. 2012 Retrovirology Result HIV L494V;S375N;S375R;V255M 122;196;76;112 127;201;81;117 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Both rM48U1BaL viruses (S375R) showed extensive cross-resistance to A12, no cross-resistance to M48; and further they were the only mutant viruses which remained completely sensitive to sCD4. 2012 Retrovirology Result HIV S375R 24 29 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. D474N is situated at the edge of the inner domain, close to the CD4bs and known to be a direct CD4 and miniCD4 contact residue. 2012 Retrovirology Result HIV D474N 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Furthermore, S375R and D474N mutations were introduced in different gp120 backgrounds (a primary subtype C strain VI829 and a primary CRF02_AG strain VI1090; Figure 2C), again confirming the pivotal role of the 375 residue in the interaction of M48U1 with envelope. 2012 Retrovirology Result HIV D474N;S375R 23;13 28;18 Env;gp120 256;68 264;73 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Furthermore, SF162 viruses resistant towards M48 and the combination of M48 and M48U1, all carrying the D474N mutation, showed substantial cross-resistance to the V3 mAb 447-52D, whereas the viruses resistant towards M48U1 only showed marginal cross-resistance to this mAb (Figure 4B). 2012 Retrovirology Result HIV D474N 104 109 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. G335R and L494V are part of or in very close proximity to the CD4bs and particularly near to the Phe43-cavity (Figure 1). 2012 Retrovirology Result HIV L494V;G335R 10;0 15;5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. In addition to the S375R/N mutation, both rM48U1SF162 viruses displayed mutations at other amino acid positions. 2012 Retrovirology Result HIV S375N;S375R 19;19 26;26 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. In contrast, a glycine to arginine substitution at position 335 and an aspartic acid to asparagine substitution at position 474 appear quite common among the different subtypes (Table 2). 2012 Retrovirology Result HIV D474N;G335R 71;15 127;63 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. In general, only 7 (out of 3045 HIV-1/SIV sequences, Table 2) naturally occurring sequences were found carrying the H105Y, V255M, or S375R mutations, suggesting that these mutations are extremely rare. 2012 Retrovirology Result HIV H105Y;S375R;V255M 116;133;123 121;138;128 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Interestingly, virus rM48U1SF162_b had, besides the S375N and V255M amino acid changes, an additional mutation close to the gp120-gp41 cleavage site; i.e. 2012 Retrovirology Result HIV S375N;V255M 52;62 57;67 gp120;gp41 124;130 129;134 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. More dramatic effects were seen with virus carrying V255M, S375N and L494V and the virus carrying D474N, with extremely poor replication in MDM. 2012 Retrovirology Result HIV D474N;L494V;S375N;V255M 98;69;59;52 103;74;64;57 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Mutations G335R, S375N, D474N and L494V displayed Kd values comparable to SF162 wild type (WT) gp120 and therefore did not have a significant impact on the affinity of HIV-1 Env for both M48 and M48U1, as reflected in a fold Kd close to 1 (Figure 2A). 2012 Retrovirology Result HIV D474N;G335R;L494V;S375N 24;10;34;17 29;15;39;22 gp120;Env 95;174 100;177 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Nevertheless, the H105Y mutation was only observed in the BaL virus and not in SF162, suggesting that this mutation may be BaL-specific. 2012 Retrovirology Result HIV H105Y 18 23 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Not surprisingly, the two viruses rCombiSF162, possessing the D474N mutation show a similar resistance profile as both rM48SF162 viruses. 2012 Retrovirology Result HIV D474N 62 67 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Of note, although D474N was found as resistance-associated mutation in 4 out of 5 viruses made resistant against M48, this residue did not significantly affect the binding (Figure 2A), nor the sensitivity to inhibition by M48 or M48U1 (Figure 2B and 2C). 2012 Retrovirology Result HIV D474N 18 23 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Of note, the S375N mutation did not significantly impact the binding affinity. 2012 Retrovirology Result HIV S375N 13 18 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. On the contrary, the mutations H105Y, V255M, S375R, and G471R, all located close to or in the CD4bs (Figure 1), have a clear impact on the Kd values. 2012 Retrovirology Result HIV G471R;H105Y;S375R;V255M 56;31;45;38 61;36;50;43 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Residues G335 and L494 are located away from the CD4bs (Figure 1) and are accompanied by either S375R/N and/or V255M. 2012 Retrovirology Result HIV S375N;S375R;V255M 96;96;111 103;103;116 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Similarly, the G471R mutation resulted in small increases in Kd, but had no apparent effect in the context of replication competent HIV. 2012 Retrovirology Result HIV G471R 15 20 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The molecular clone with an arginine instead of a serine at position 375 had an entry efficiency of only 33% relative to WT virus. 2012 Retrovirology Result HIV R375R 28 72 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The mutant virus carrying H105Y showed a clear reduction in infectivity (approximately 1 log) in MDM, confirming the low entry efficiency observed in TZM-bl cells. 2012 Retrovirology Result HIV H105Y 26 31 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The other M48 resistant viruses, rM48SF162_a and rM48SF162_b (D474N), showed a different cross-resistance profile. 2012 Retrovirology Result HIV D474N 62 67 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The other mutated positions, S375N, G471R, and D474N affected entry efficiency to a lesser extent, with mean percentages of infection relative to the WT clone ranging from 50 to 68%. 2012 Retrovirology Result HIV D474N;G471R;S375N 47;36;29 52;41;34 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The second SF162 virus resistant to the combination of both miniproteins (rCombiSF162_b) revealed two additional mutations in the outer domain, namely G471E and L494V. 2012 Retrovirology Result HIV G471E;L494V 151;161 156;166 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The SF162 viruses, resistant against M48 (rM48SF162_a and rM48SF162_b) and against the combination of M48U1 and M48 (rCombiSF162_a), displayed the same mutational pattern where the aspartic acid at position 474 (in C5) is altered into an asparagine (D474N). 2012 Retrovirology Result HIV D474N 250 255 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The virus rM48BaL (H105Y) was not only resistant to M48, but also to M48U1 and sCD4. 2012 Retrovirology Result HIV H105Y 19 24 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. To answer this question, mutations H105Y, V255M, S375R, S375N, G471R, and D474N were introduced in the SF162 WT env gene using site-directed mutagenesis (Table 3). 2012 Retrovirology Result HIV D474N;G471R;H105Y;S375N;S375R;V255M 74;63;35;56;49;42 79;68;40;61;54;47 Env 112 115 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. To explore the contribution of the different amino acid mutations in the interaction between gp120 and the miniCD4 proteins M48 and M48U1, site-directed mutants of SF162 env were generated carrying one of the RAMs: H105Y, V255M, G335R, S375R, S375N, G471R, D474N or L494V (see Table 3 for an overview of SDMs). 2012 Retrovirology Result HIV D474N;G335R;G471R;H105Y;L494V;S375N;S375R;V255M 257;229;250;215;266;243;236;222 262;234;255;220;271;248;241;227 gp120;Env 93;170 98;173 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. To further validate these observations, the H105Y, V255M, S375R/N, G471R and D474N mutant SF162 envelopes were also evaluated in the context of replication competent pBRNL4.3 molecular clones (Figure 2B). 2012 Retrovirology Result HIV D474N;G471R;H105Y;S375N;S375R;V255M 77;67;44;58;58;51 82;72;49;65;65;56 Env 96 105 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Two mutations, H105Y and V255M, had a dramatic negative effect on entry efficiency, resulting in respectively 1% and 2% of infection relative to WT virus (Figure 3A). 2012 Retrovirology Result HIV H105Y;V255M 15;25 20;30 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. We also tested whether miniCD4 protein induced resistance affected the sensitivity towards the CD4-induced (CD4i) monoclonal antibody 17b and confirmed that mutant viruses carrying D474N or S375R/N or V255M were resistant to inhibition by 17b (Figure 4B). 2012 Retrovirology Result HIV D474N;S375N;S375R;V255M 181;190;190;201 186;197;197;206 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. We identified D474N as single resistance-associated mutation in the viruses rM48SF162_a, rM48SF162_b, and rCombiSF162_a. 2012 Retrovirology Result HIV D474N 14 19 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Whereas binding of M48 to H105Y mutant monomer gp120 was affected (approx. 2012 Retrovirology Result HIV H105Y 26 31 gp120 47 52 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. With the exception of H105Y, results correlated with binding affinity studies and confirmed the importance of V255M and S375R/N in resistance towards M48 and M48U1. 2012 Retrovirology Result HIV H105Y;S375N;S375R;V255M 22;120;120;110 27;127;127;115 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. Also, a cluster of three had transmitted M41L. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV M41L 41 45 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. Between 1995 and 2010, prevalence of K103N/S increased from 1.9% to 8.0% (Ptrend=0.04). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;K103S 37;37 44;44 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. D67N(P=0.03), K70R(P=0.06), M184V(P=0.11), L210W(P=0.11), and K219Q(P=0.02) decreased during the study period. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV K219Q;K70R;L210W;M184V;D67N 62;14;43;28;0 67;18;48;33;4 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. Mutations M41L (3.7%), T215Y/F/S/D/C/E (4.0%), K103N/S (4.7%) and L90M were most prevalent. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;K103S;L90M;M41L;T215C;T215D;T215E;T215F;T215S;T215Y 47;47;66;10;23;23;23;23;23;23 54;54;70;14;38;38;38;38;38;38 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. One clustered pair had M46L, another had T215D, and a third had K103N, D67N and K219Q. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV D67N;K103N;K219Q;M46L;T215D 71;64;80;23;41 75;69;85;27;46 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. The presence of M184V was associated with a lower HIV-1 log10viral load (4.44 vs. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 16 21 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. As shown in Table 3, the PR-associated mutations with the highest degree of expression from 2006 to 2010 was L63P with frequencies of (525 of 707, 74.3%), (429 of 608, 70.6%), (494 of 706, 70.0%), (238 of 340, 70.0%), and (93 of 139, 66.9%), respectively. 2012 AIDS research and treatment Result HIV L63P 109 113 PR 25 27 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. I13V was the third highest mutation for 2006, 2007, and 2009 and was recorded in (155 of 707, 21.9%), (190 of 608, 31.3%), and (109 of 340, 32.1%) of the specimens, respectively. 2012 AIDS research and treatment Result HIV I13V 0 4 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. K103N was also among the most important mutations since it was the third highest mutation for 2006 and remained in second place for the duration of the study with incidences of (152 of 707, 21.5%), (114 of 608, 18.8%), (143 of 706, 20.3%), (58 of 340, 17.1%), and (12 of 139, 8.6%) during the five-year period. 2012 AIDS research and treatment Result HIV K103N 0 5 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. Likewise, the third place corresponded to I62V in 2008 (211 of 706, 29.9%) and 2010 (37 of 139, 26.6%). 2012 AIDS research and treatment Result HIV I62V 42 46 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. M184V was the dominant mutation for all the years included in this study with frequencies of (322 of 707, 45.5%), (253 of 608, 41.6%), (206 of 706, 29.2%), (88 of 340, 25.9%), and (14 of 139, 10.1%), respectively. 2012 AIDS research and treatment Result HIV M184V 0 5 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. M36I was the second most common mutation for 2006 (164 of 707, 23.2%), while this position was occupied by V77I for the reminder of the study with prevalences of (201 of 608, 33.1%), (222 of 706, 31.4%), (125 of 340, 36.8%), and (45 of 139, 32.4%). 2012 AIDS research and treatment Result HIV V77I;M36I 107;0 111;4 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. M41L was the second most common mutation for 2006 and the third most common mutation for 2007, 2008, and 2010 with prevalences of (157 of 707, 22.2%), (106 of 608, 17.4%), (79 of 706, 11.2%), and (11 of 139, 7.9%) for these years. 2012 AIDS research and treatment Result HIV M41L 0 4 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. Statistically significant differences between men and women were observed for K70R (P = 0.04) and K219Q (P = 0.03) in 2006, K103N (P = 0.02) in 2007, K219E (P = 0.03) in 2009 (data not shown), and V118I (P = 0.03) in 2010. 2012 AIDS research and treatment Result HIV K103N;K219E;K219Q;K70R;V118I 124;150;98;78;197 129;155;103;82;202 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. Statistically significant differences between men and women were recorded for A71V (P = 0.05) and L90M (P = 0.04) in 2006, and M36I (P = 0.005) in 2008. 2012 AIDS research and treatment Result HIV A71V;L90M;M36I 78;98;127 82;102;131 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. V118I was the third highest mutation for 2009 with an occurrence of 38 of 340 (11.2%). 2012 AIDS research and treatment Result HIV V118I 0 5 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Eight samples exhibited K70R with Sanger and the corresponding UDPS values ranged from 34.50 to 100%. 2012 PloS one Result HIV K70R 24 28 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. If we only consider positions 65 found not to have K65R with Sanger (25 samples), the quantities of K65R ranged from <0.4% to 0.80% (0.162+-0.22 SD). 2012 PloS one Result HIV K65R;K65R 51;100 55;104 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. In the two isolates with K65R by Sanger, percentages of K65R by UDPS were 27% and 87%. 2012 PloS one Result HIV K65R;K65R 25;56 29;60 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K65R ranged from <0.4% to 3.08% (mean 0.66+-0.76 standard deviation, SD). 2012 PloS one Result HIV K65R 0 4 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K70R was <0.4% by UDPS in all isolates from naive patients. 2012 PloS one Result HIV K70R 0 4 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K70R with UDPS ranged from <0.4% to 100%. 2012 PloS one Result HIV K70R 0 4 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Most of them exhibited the M184V mutations to 3TC of the regimen plus TAMs to d4T and/or AZT and DRMs to NNRTIs. 2012 PloS one Result HIV M184V 27 32 NNRTI 105 111 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Only two samples (455 and 493) bore a K65R mutation, one (455) cumulating K65R and the Q151M nucleoside analog mutation (NAM). 2012 PloS one Result HIV K65R;K65R;Q151M 38;74;87 42;78;92 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Quantitation of K65R by UDPS ranged from <0.4% to 87%. 2012 PloS one Result HIV K65R 16 20 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Regarding positions 70 found not to have the K70R mutation with Sanger (19), all of them were <0.4% for 70R by UDPS except two samples (470 and 489 with values of 1.80 and 4.40% respectively). 2012 PloS one Result HIV K70R 45 49 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. As for the V66A mutant, only three out of the five residues are located in this area. 2012 Journal of molecular modeling Result HIV V66A 11 15 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. As was observed for the WT, a more thermodynamically stable structure is attained for V66A mutant after the MD, with an increase of five helices (three to eight) after simulation completion. 2012 Journal of molecular modeling Result HIV V66A 86 90 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. For both WT and V66A MT Nef variants, the location of the SMR domain is favorably placed on the outer surface of the 3D structure, ideally unencumbered and available to interact with either solvent or other protein structures. 2012 Journal of molecular modeling Result HIV V66A 16 20 Nef 24 27 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. For our purposes, the RMSD reference geometries chosen corresponded to the lowest energy structure conformation obtained from 50 ns MD for both wild-type (WT) and V66A (MT) HIV-1 Nef simulations. 2012 Journal of molecular modeling Result HIV V66A 163 167 Nef 179 182 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. For the V66A mutant at 0 ns MD, amino acids in positions one and four of the SMR motif (Ala-66 and Pro-69) have been moved from the favored position to the allowed position. 2012 Journal of molecular modeling Result HIV V66A 8 12 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. For the V66A mutant SMR, five putative pockets were also generated by MOLEGRO, of which only one was in a correct proximity for the amino acids of the SMR. 2012 Journal of molecular modeling Result HIV V66A 8 12 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. For the V66A mutant, with the SMR sequence AGFPV, the distance measurement from the N-terminal amino acid residue to the SMR residue Ala-66 shows a decrease of 27.4 A from 54.6 A at 0 ns MD to 27.2 A after 30 ns MD (Table 3). 2012 Journal of molecular modeling Result HIV V66A 8 12 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. It is also important to note that there is variability in the V66A amino acid movement durjng the couse of MD: Pro-69 and Ala-66 for 0 ns MD, and Ala-66 and Gly-67 after 30 ns MD. 2012 Journal of molecular modeling Result HIV V66A 62 66 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. Of these representative sequences, there were only three examples of amino acid substitutions in the SMR, with changes from Val-66 to Glycine (Italian Cohort), Pro-69 to Serine (US cohort) and Val-70 to Glycine (US cohort). 2012 Journal of molecular modeling Result HIV P69S;V66G;V70G 160;124;193 176;141;210 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. The Ramachandran plot analysis shows the favored location of amino acids comprising the SMR motif in both WT and V66A mutant (MT) forms. 2012 Journal of molecular modeling Result HIV V66A 113 117 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. The ranking by importance therefore, of all the V66A mutant SMR amino acid residues (highest to lowest) would thus be Gly-67, Ala-66, Phe-68, Pro-69 and Val-70. 2012 Journal of molecular modeling Result HIV V66A 48 52 22659320 Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor. 8A, lane 4) binds to PRM1, one of our constructs of TFR-PR, bearing a fortuitous K43E substitution mutation which does not affect autoprocessing or resultant catalytic activity, failed to bind (lane 3). 2012 Journal of molecular biology Result HIV K43E 81 85 PR;PR 21;56 23;58 22659320 Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor. An active site mutation, D25N, which abolishes catalytic activity, was introduced to prevent self-degradation (autoproteolysis), which would interfere with analysis of the data, and also to increase the Kd of PR2 and thus to facilitate interaction with the antibody. 2012 Journal of molecular biology Result HIV D25N 25 29 PR 209 212 22659320 Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor. Subsequent experiments revealed that natural variant PRN, which has an R41K substitution, also is not recognized by the human antibody. 2012 Journal of molecular biology Result HIV R41K 71 75 22659320 Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor. Thus antibody binding is reasonably tolerant of conservative substitutions (PR2) as well as the non-conservative substitution of Pro for Thr at position 4 in PRO. 2012 Journal of molecular biology Result HIV T4P 129 154 PR 76 79 22659320 Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor. We have obtained conclusive biophysical evidence for dimer disruption by formation of a PR2D25N monomer/scFv complex using molecular mass analysis of the complex in the presence and absence of an active site inhibitor that is expected to stabilize the dimer (although weakly because of reduced affinity to the D25N mutant). 2012 Journal of molecular biology Result HIV D25N 310 314 PR 88 91 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Additional RT mutations with the K65R included K103N and V106M. 2012 AIDS (London, England) Result HIV K103N;K65R;V106M 47;33;57 52;37;62 RT 11 13 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Of the remaining 9 patients, 4 (44.4%) had the K65R mutation. 2012 AIDS (London, England) Result HIV K65R 47 51 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. The following factors were evaluated, using regression analysis, to determine their association with K65R amongst patients failing a TDF-containing first-line ART: age, gender, regimen, CD4 count, viral load, duration of ART and prior AIDS-defining illnesses. 2012 AIDS (London, England) Result HIV K65R 101 105 AIDS 235 239 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Therefore if these 9 patients were excluded from the 33 total patients with amplifiable virus on TDF, then 19 (79.2%) had the K65R mutation. 2012 AIDS (London, England) Result HIV K65R 126 130 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Twenty-three (69.7%) of the 33 patients with VF and amplifiable virus had the K65R mutation. 2012 AIDS (London, England) Result HIV K65R 78 82 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Two (3.8%) of these patients had VF and one had the K65R mutation. 2012 AIDS (London, England) Result HIV K65R 52 56 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Both A44L and C11R are virulence factors that do not affect vaccinia virus replication in vitro; and we have shown that deletion of A44L or C11R (Cottingham et al., unpublished data) does not affect MVA immunogenicity. 2012 PloS one Result HIV A44L;A44L;C11R;C11R 5;134;15;143 9;138;19;147 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Closer inspection of the sequences upstream of the MVA orthologs of K6L (MVA026L) and B2R (MVA168R) revealed fragmentation due to small deletions at the 5' ends which we had overlooked during design of the constructs (Table 2). 2012 PloS one Result HIV K6L 68 71 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. In both readouts, and in other independent experiments (data not shown), the trend was the same, in that pF11L and pC11L elicited the highest CD8+ T cell frequencies, similar to SSP, with p7.5 and pB8R and A44L exhibiting slightly lower immunogenicity. 2012 PloS one Result HIV A44L 206 210 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. In the presence of AraC, the B8R, F11L, A44L and C11R promoters at their authentic loci (pB8R, pF11L, pA44L and pC11R) produced rLuc levels similar to that produced by p7.5 or SSP; however, in the absence of the inhibitor, the late promoter activity of p7.5 and SSP allowed higher protein expression. 2012 PloS one Result HIV A44L;C11R;F11L 40;49;34 44;53;38 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. lacking C11R, encoding the vaccinia growth factor) surprisingly exhibited a more rapid increase in GFP fluorescence and reached a slightly higher plateau. 2012 PloS one Result HIV C11R 8 12 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. MVA Orthologs of K6L and B2R are Truncated and Fragmented Pseudogenes. 2012 PloS one Result HIV K6L 17 20 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. The recombinant viruses employing the non-authentic initiation codons of K6L and B2R were not investigated further in this study. 2012 PloS one Result HIV K6L 73 76 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. These ATGs lie much closer to the mean 40 bp distance from the early transcriptional start sites and initiate severely truncated ORFs comprising the authentic N-terminal 14 plus 1 nonsense amino acids (K6L) or 30 plus 2 nonsense amino acids (B2R), as the result, in both cases, of a 20 bp deletion in MVA relative to vaccinia virus (positions 24691..24692 and 152186..152187 in U94848). 2012 PloS one Result HIV K6L 202 205 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Vaccinia virus K5L/K6L (and WR036) are fragments of CPXV045; and vaccinia virus B2R/B3R are fragments of CPXV197. 2012 PloS one Result HIV K5L;K6L 15;19 18;22 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. We did not exclude F11L on this basis, but instead reverted an MVA-specific substitution just upstream of the initiation codon back to identity with vaccinia virus (Table 2). 2012 PloS one Result HIV F11L 19 23 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. We mistakenly targeted the initiation codons of MVA027L and MVA168R without realising until later that these do not contain the authentic K6L and B2R initiation codons, which are found further upstream (see Table 2). 2012 PloS one Result HIV K6L 138 141 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Comparison of sequences across the region covered by peptide ARP7035.19 revealed an identical sequence for W61D and IIIB with only a single amino acid change at position 213 (A to T) for the equivalent SF33 peptides ARP7117.18 that may account for absence of a T cell response (Additional file 1: Table S1). 2012 Retrovirology Result HIV A213T;W61D 170;107 182;111 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Five peptides across C1 and two within C2 that showed homology between W61D, IIIB and SF33 sequences formed the C1 peptide pool (Table 7 ). 2012 Retrovirology Result HIV W61D 71 75 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. For analysis of T cell proliferative responses, peptides pools were selected on the basis of sequence homology of at least 9 consecutive amino acid residues, sufficient to constitute a shared T cell epitope, between W61D and IIIB or SF33 HIV-1 envelope sequences. 2012 Retrovirology Result HIV W61D 216 220 Env 244 252 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Four further peptides within C2 that showed homology between W61D and IIIB but not SF33 formed the C2 pool and this was compared with the corresponding SF33 C2 pool (Table 7 ). 2012 Retrovirology Result HIV W61D 61 65 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. G19 made a broad proliferative T cell response that was significant against W61D V1/V2, V3 and V4 peptide pools, compared with corresponding SF33 peptide pools (Figure 5A). 2012 Retrovirology Result HIV W61D 76 80 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Peptides across variable loops 1, 2, 3 and 4 showed little homology between W61D, IIIB and SF33 sequences and were divided into 3 pools that approximately covered V1/V2, V3 and V4 regions for each envelope sequence (Table 7 ). 2012 Retrovirology Result HIV W61D 76 80 Env 197 205 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Responses against IIIB and SF33 V1/V2, V3 and V4 peptide pools were greatly reduced by comparison with W61D responses. 2012 Retrovirology Result HIV W61D 103 107 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Two peptides across C3 showed homology between W61D and SF33 but not IIIB formed the C3 pool (Table 7 ). 2012 Retrovirology Result HIV W61D 47 51 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. As described in detail previously and summarized in Table 1 and Figure 1, five animals were infected at birth or at juvenile age with either wild-type SIVmac251 (n = 3), a K65R isolate derived from SIVmac251 (n = 1) or RT-SHIV (a chimeric SIV containing HIV-1 RT). 2012 Retrovirology Result HIV K65R 172 176 RT;RT 219;260 221;262 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. For animal 33091, plasma collected at the time of tenofovir withdrawal and at the time of euthanasia (41 weeks after tenofovir withdrawal) had pure K65R populations; most other RT mutations were found in both samples (N69S, Y115F, I118V, D121H, V201A, S211N), while some mutations were found in only 1 sample (K40E and R82R/K at time of tenofovir withdrawal; K43E at time of euthanasia). 2012 Retrovirology Result HIV D121H;I118V;K40E;K43E;K65R;N69S;R82K;R82R;S211N;V201A;Y115F 238;231;310;359;148;218;319;319;252;245;224 243;236;315;363;152;222;325;325;257;250;229 RT 177 179 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. In summary, there was no evidence of reversion from K65R to wild-type virus after tenofovir withdrawal. 2012 Retrovirology Result HIV K65R 52 56 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Nearly all of these mutations have been described previously in K65R SIV isolates of animal 33091 and other tenofovir-treated animals. 2012 Retrovirology Result HIV K65R 64 68 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Quantitation and genotypic analysis of K65R viral mutants. 2012 Retrovirology Result HIV K65R 39 43 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Real-time PCR methodology and population sequencing was used to monitor and quantitate K65R viral mutants after tenofovir withdrawal. 2012 Retrovirology Result HIV K65R 87 91 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. While plasma viral RNA levels in animals 30577, 33088 and 32186 were too low to amplify, viral RNA in the tonsil of animal 32186 revealed a pure K65R population with the additional RT mutations of N69S, I118V; these mutations were found previously in this animal. 2012 Retrovirology Result HIV I118V;K65R;N69S 203;145;197 208;149;201 RT 181 183 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. 11A shows that the progression of reverse transcription from R-U5 to later products (reported as the percentage of R-U5) is only reduced slightly with all of the mutant infections compared to WT with the exception of F16A/W37A, which has a more severe effect. 2013 Virus research Result HIV F16A;W37A 217;222 221;226 RT 34 55 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. 11A), overall the levels of 2-LTR circles (TOT) are quite similar to WT virus on a percent R-U5 basis, suggesting that completion of full-length vDNA leading to circles is not significantly affected; the lack of circles for the F16A/W37A mutant is inconclusive with regard to end-degradation or LTR completion as the quantities of circles were consistently below the level of detection of our qPCR assay. 2013 Virus research Result HIV F16A;W37A 228;233 232;237 LTR;LTR 30;295 33;298 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. 4 shows representative DNA stretching and relaxation cycles in the presence of saturating amounts of F16W (panel A) or F16W/W37F (panel B) NC. 2013 Virus research Result HIV F16W;F16W;W37F 101;119;124 105;123;128 NC 139 141 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. 5C), reflecting slow re-annealing kinetics, significant DNA strand separation, and slow dissociation of F16A/W37A from ssDNA. 2013 Virus research Result HIV F16A;W37A 104;109 108;113 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. Additionally, the NCp7 band for the F16A/W37A mutant appeared less intense than the others, which may be due to less efficient processing of the Gag precursor (Pr55Gag) and/or possible alteration of epitopes recognized by the goat antiserum that was used. 2013 Virus research Result HIV F16A;W37A 36;41 40;45 Gag;NC;PR 145;18;160 148;20;162 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. As shown in Table 1, the microTAR RNA binding affinity of the W37A and F16A/W37A aromatic replacement mutants is within about a factor of two of that observed for WT NC, while the affinity of the F16A mutant is about 7-fold greater than that of WT NC. 2013 Virus research Result HIV F16A;F16A;W37A;W37A 71;196;62;76 75;200;66;80 NC;NC 166;248 168;250 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. F16A, W37A, and F16A/37A NC display 2-, 32-, and ~1000-fold reduced affinity for (TG)4, respectively. 2013 Virus research Result HIV F16A;W37A;F16A 16;6;0 20;10;4 NC 25 27 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. However, when a higher concentration of F16A/W37A NC was used to compensate for reduced binding affinity, the rate of annealing approached that of WT NC. 2013 Virus research Result HIV F16A;W37A 40;45 44;49 NC;NC 50;150 52;152 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. In contrast, W37A NC displays reduced binding to both nucleic acids, with a larger reduction in TG4 binding. 2013 Virus research Result HIV W37A 13 17 NC 18 20 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. In the single-round TZM-bl assay, the W37F mutant was as infectious as WT HIV-1, and the Fl 6W and F16W/W37F mutants had 2- and 5-fold reduced titers, respectively. 2013 Virus research Result HIV F16W;W37F;W37F 99;38;104 103;42;108 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. Note that F16A has a higher affinity than WT NC for microTAR, but binds similarly to TG4 as WT (Table 1). 2013 Virus research Result HIV F16A 10 14 NC 45 47 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. On a per particle basis, the F16A mutant is reduced slightly as well, and the W37A mutant is even lower. 2013 Virus research Result HIV F16A;W37A 29;78 33;82 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. One can also speculate that binding may be tighter to microTAR for F16A compared to WT NC, as the mutant protein may be able to adopt additional conformations that (i) are sterically hindered due to the larger side chain of Phe compared to Ala and (ii) may also be constrained due to the aromatic ring interactions with nucleobases. 2013 Virus research Result HIV F16A 67 71 NC 87 89 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The F16A mutant has a titer that is 104-fold lower than wild type, and no replication was detected in the W37A and F16A/W37A mutants, even in the undiluted samples. 2013 Virus research Result HIV F16A;F16A;W37A;W37A 4;115;106;120 8;119;110;124 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The F16A mutant was ~90% reduced in titer and the other two mutants W37A and F16A/W37A had titer reductions of >99% compared to WT. 2013 Virus research Result HIV F16A;F16A;W37A;W37A 4;77;68;82 8;81;72;86 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The F16A/W37A variant has the greatest reduction of all, with a 625-fold reduced production of the R-5'UTR plus-strand transfer intermediate. 2013 Virus research Result HIV F16A;W37A 4;9 8;13 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The F16W, W37F, and F16W/W37F mutants were very similar to the WT sample in these analyses. 2013 Virus research Result HIV F16W;F16W;W37F;W37F 4;20;10;25 8;24;14;29 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The levels are similar to WT HIV-1 for all mutants except for W37A and F16A/W37A, which are 2- to 5-fold lower, respectively. 2013 Virus research Result HIV F16A;W37A;W37A 71;62;76 75;66;80 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The levels of intravirion DNA are similar to WT for the F16W and the W37F mutants and slightly elevated (~12-fold for R-U5 and 5-fold for R-5'UTR) for the F16W/W37F mutant. 2013 Virus research Result HIV F16W;F16W;W37F;W37F 56;155;69;160 60;159;73;164 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The mutants where the aromatic character of residues 16 and 37 are maintained show levels of reverse transcription intermediates that are very similar to WT with a minor reduction for the F16W/W37F mutant. 2013 Virus research Result HIV F16W;W37F 188;193 192;197 RT 93 114 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The reduced DNA binding affinity of the mutant NC proteins compared to WT HIV-1 NC is demonstrated by the fact that while the effects of WT HIV-1 NC on the DNA stretching curves saturate at 10 nM concentration, it takes 30 nM of HIV-1 F16W and F16W/W37F to reach saturation (data not shown). 2013 Virus research Result HIV F16W;W37F 244;249 248;253 NC;NC;NC 47;80;146 49;82;148 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The study by showed that while WT NC could restrict the local mobility of a flexible oligodeoxynucleotide, the F16A NC mutant could not. 2013 Virus research Result HIV F16A 111 115 NC;NC 34;116 36;118 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. There are some uncleaved (Pr55Gag) and partially cleaved Gag precursors detected for the F16A-, W37A- and F16A/W37A-mutant viruses. 2013 Virus research Result HIV F16A;F16A;W37A;W37A 89;106;96;111 93;110;100;115 Gag;PR 57;26 60;28 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. This same phenomenon is observed with the mutants in this study with near WT levels of R-U5 and R-5'UTR ERT with the F16W and W37F mutants and a slight reduction (~5- to 9-fold) in ERT activity with the F16W/W37F mutant. 2013 Virus research Result HIV F16W;F16W;W37F;W37F 117;203;126;208 121;207;130;212 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. This very small slope of the force-extension curve at high forces is even more pronounced in the stretching curves of the double aromatic to Ala substitution mutant, F16A/W37A, presented in. 2013 Virus research Result HIV F16A;W37A 166;171 170;175 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. Thus, although the higher binding affinity of F16A NC to microTAR is unexpected, the variable and nucleic acid sequence-dependent contributions of F16 and W37 to binding observed here are consistent with previous results. 2013 Virus research Result HIV F16A 46 50 NC 51 53 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. Thus, within the virion, where the local NC concentration is estimated to be 100 mM, the decreased annealing activity of F16A/W37ANC is not likely to be important. 2013 Virus research Result HIV F16A;W37A 121;126 125;130 NC 41 43 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. To test this hypothesis, we constructed several mutants in which one or both aromatic residues are replaced by either Ala or by another aromatic residue: F16W, F16W/W37F, F16A, W37A, and F16A/W37A, as shown in. 2013 Virus research Result HIV F16A;F16A;F16W;F16W;W37A;W37A;W37F 171;187;154;160;177;192;165 175;191;158;164;181;196;169 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. With all of the mutants except F16A/W37A. 2013 Virus research Result HIV F16A;W37A 31;36 35;40 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. Again for R5 HIV-1 strain SF162, both D30A and D112A variants were reduced in potency compared to the wild-type protein by several hundred fold, while the D70A mutant was worse than the wild-type protein, but better than the other point mutants. 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 47;38;155 52;42;159 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. As shown in Table 3 and Figure 6D, while wild-type GRFT inhibited HIV strain ADA with an EC50 of 10.5 pM, the D30A mutant and D112A mutant were about 1,000-fold less potent (20.3 and 6.57 nM, respectively). 2012 Molecular pharmaceutics Result HIV D112A;D30A 126;110 131;114 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. However, since this set of gp120 binding and antiviral data only includes the ADA strain, it is premature to assume that the superior antiviral activity of the D70A mutant versus the other mutants is a general phenomenon. 2012 Molecular pharmaceutics Result HIV D70A 160 164 gp120 27 32 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. In all cases, the triple mutant D30A/D70A/D112A was a very poor antiviral inhibitor, with an EC50 of 95.3 nM for the IIIB strain, and EC50 values being higher than the maximum concentration tested (500 nM) against the R5 HIV-1 strains (Figure 6D and Table 3). 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 42;32;37 47;36;41 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. In general, the GRFT point mutant D70A, having a mutation at the so-called Pocket 3, repeatedly appeared to bind the worst in these experiments under the same conditions, although ELISA experiments are not quantitative. 2012 Molecular pharmaceutics Result HIV D70A 34 38 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. In this case the D70A variant had quite similar antiviral activity as the other point mutants. 2012 Molecular pharmaceutics Result HIV D70A 17 21 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. The D30A and D112A variants were approximately 300-fold lower in anti-HIV potency than wild-type GRFT, and the D70A mutant exhibited about a 10-fold greater antiviral potency than the other two point mutants. 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 13;4;111 18;8;115 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. The D70A mutant was somewhat a better inhibitor than the other point mutants, with an EC50 of 2.63 nM. 2012 Molecular pharmaceutics Result HIV D70A 4 8 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. The triple GRFT mutant D30A/D70A/D112A binds very poorly to gp120, showing only a low signal increase at the high-tested amount of 1.28 microM. 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 33;23;28 38;27;32 gp120 60 65 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. The triple mutant D30A/D70A/D112A did not show a binding signal when exposed to gp120 at 12 nM (Table 2). 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 28;18;23 33;22;27 gp120 80 85 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. When this triple mutant D30A/D70A/D112A was titrated with mannose, the HSQC spectra showed essentially no change for any concentration tested, up to 23 mM mannose, indicating no binding (Figure S6). 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 34;24;29 39;28;33 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. Whereas the wild-type GRFT potently prevented syncytia formation in the cocultures at an EC50 of 1.91 +- 1.23 nM, the D30A, D70A and D112A point mutants showed EC50 values of 67.4 +- 39.7 nM, 88.6 +- 23.8 nM and 36.1 +- 14.3 nM, respectively. 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 133;118;124 138;122;128 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. While each point mutant of GRFT showed reduced binding to gp120 derived from both X4 and R5 HIV-1 strains, the effect was small, with D30A and D112A generally exhibiting an as little as 2-fold reduction in binding compared to the wild-type protein, while the point mutant D70A showed only a 3-fold reduction in affinity. 2012 Molecular pharmaceutics Result HIV D112A;D30A;D70A 143;134;272 148;138;276 gp120 58 63 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. After controlling for HIV-1 subtype, their association with each other diminished (OR 3.16 [0.8-12.4], P= 0.10), thus highlighting separate independent associations of G335D and A371V with viral subtype (G335D OR 12.0 [2.8-52.6], P <0.005; A371V OR 7.0 [2.3-21.7], p<0.005). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV A371V;A371V;G335D;G335D 178;240;168;204 183;245;173;210 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Eight CD mutations were identified: G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), 318F (2.1%), G333E (2.1%) and A360V (2.1%). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV A360V;A371V;E399D;G333E;G335D;N348I;V365I 137;51;66;120;36;80;94 142;56;71;125;41;85;99 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. For nevirapine, the protective effect of G335D was also evident (OR 0.09, P= 0.034), however it was difficult to separate the effect of subtype. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G335D 41 46 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Further univariate analysis dichotomizing subtype as CRF02_AG (n=50) versus CRF06_CPX (n=12) attenuated the association of CRF02_AG with reduced likelihood of phenotypic resistance to NVP (OR 0.12 [0.02-1.24], P= 0.078, but remained significant after controlling for A371V (OR 0.50 [0.003-0.66], P= 0.023). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV A371V 267 272 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. G190A (10.4% prevalence) was negatively associated with CRF02_AG (OR 0.14 [0.02-0.8], P= 0.028) amongst first-line failures (N= 76) in multivariate modeling. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A 0 5 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. However, K103N, Y181C/I/V mutations and G190A were not collinear and were absent in 27.1% of isolates with phenotypic nevirapine resistance. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K103N;Y181C;Y181I;Y181V 40;9;16;16;16 45;14;25;25;25 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. In analysis limited to only CRF02_AG (N= 67), there was no longer an association between K103N and G335D (P= 0.549, Fisher's exact). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G335D;K103N 99;89 104;94 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. In the multivariate model, nevirapine resistance was less likely with subtype CRF02_AG (OR 0.17 [0.03-0.90], P= 0.037) despite 100% prevalence of K103N within CRF02_AG virus. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 146 151 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. In the multivariate model, there remained a significant association with reduced risk of resistance to etravirine (OR 0.27 [0.08-0.94], P=0.040) in the presence of G335D. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G335D 164 169 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. In univariate analysis, G335D (OR 19.9 [95%CI 5.1-78.2], P <0.005) and A371V (OR 10.8 [3.9-30.0], P <0.005) were significantly associated with CRF02_AG, and with each other (OR 8.75 [2.7-28.3], P <0.005). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV A371V;G335D 71;24 76;29 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. On univariate analysis, G335D was associated with reduced risk of resistance to nevirapine (OR 0.12 [0.01-0.99], P= 0.049) and etravirine (OR 0.31 [0.09-1.00], P= 0.05), but not efavirenz (OR 0.34 [0.09-1.3], P= 0.121). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G335D 24 29 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. On univariate analysis, M184V/I was associated with 'other' CD mutations (OR 2.91 [1.03-8.2], P= 0.043). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V 24;24 31;31 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. The most prevalent N-terminal mutations were M184V/I (55.2%), Y181C/I/V (29.2%), K103N (20.8%) and TAMs (19.8%). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;M184I;M184V;Y181C;Y181I;Y181V 81;45;45;62;62;62 86;52;52;71;71;71 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. The only other prevalent NVP-specific resistance mutations were Y181C/I/V (29.0%) and G190A (7.3%), and they were always associated with phenotypic nevirapine resistance. 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;Y181C;Y181I;Y181V 86;64;64;64 91;73;73;73 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. The protection remained significant in those without K103N or Y181C/V/I mutations (OR 0.04 [0.005-0.4], P= 0.008, N=37). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C;Y181I;Y181V 53;62;62;62 58;71;71;71 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. The reduction of resistance to etravirine is further highlighted when controlling for Y181C/V/I mutations and presence of K103N (OR 0.10 [0.02-0.7], P= 0.020). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;Y181C;Y181I;Y181V 122;86;86;86 127;95;95;95 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Within the examined cohort, K103N mutation was only present in subtype CRF02_AG (p <0.005) and always occurred with G335D (P= 0.019). 2012 Journal of acquired immune deficiency syndromes (1999) Result HIV G335D;K103N 116;28 121;33 22860080 Long-term hepatitis B virus (HBV) response to lamivudine-containing highly active antiretroviral therapy in HIV-HBV co-infected patients in Thailand. Six patients had HIV RNA load above 500 copies/mL and all presented the M184I/V mutations associated with HIV resistance to 3TC. 2012 PloS one Result HIV M184I;M184V 72;72 79;79 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Addition of R284K to the TAM1 cluster produced a subtle increase in the IC50 for AZT, which was 5.8 times higher than the IC50 obtained with the WT virus. 2012 Retrovirology Result HIV R284K 12 17 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Although mutant RTs M41L/L210W/T215Y and M41L/L210W/T215Y/R284K showed remarkable ATP-dependent phosphorolytic activity, the presence of R284K had a minimal impact on rescue DNA polymerization initiated from NRTI-terminated primers. 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y;R284K 25;46;20;41;58;31;52;137 30;51;24;45;63;36;57;142 NRTI;RT 208;16 212;19 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Amino acid substitutions D67N, L74I, K223E and L228H associate with the TAM2 cluster, while V118I, V179I, M184V and R284K are linked to cluster (2) formed by mutations of the TAM1 pathway. 2012 Retrovirology Result HIV D67N;K223E;L228H;L74I;M184V;R284K;V118I;V179I 25;37;47;31;106;116;92;99 29;42;52;35;111;121;97;104 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Among those four mutations, R284K was the only one that showed a positive value (0.356) associated with factor 2, while having negative values for all other factors included in the analysis (Additional file 1: Table S2). 2012 Retrovirology Result HIV R284K 28 33 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. An increased frequency of RNase H secondary cleavages was also observed with 38Trna/25PGA in reactions catalyzed by the M41L/L210W/T215Y/R284K RT. 2012 Retrovirology Result HIV L210W;M41L;R284K;T215Y 125;120;137;131 130;124;142;136 RT 143 145 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. As expected, phenotypic drug susceptibility assays showed that the combination M41L/L210W/T215Y had a significant impact on AZT resistance, but a minor effect on HIV-1 susceptibility to d4T, tenofovir and emtricitabine (Table 2). 2012 Retrovirology Result HIV L210W;M41L;T215Y 84;79;90 89;83;95 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Contribution of R284K to ATP-mediated rescue of primers terminated with NRTIs. 2012 Retrovirology Result HIV R284K 16 21 NRTI 72 77 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. dissociation of the RT-DNA complex), the observed kcat differences between M41L/L210W/T215Y and M41L/L210W/T215Y/R284K RTs are expected to be relevant because both enzymes have similar koff values. 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 80;101;75;96;113;86;107 85;106;79;100;118;91;112 RT;RT 20;119 22;122 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. For example, in assays carried out with 31Trna/21P, the amount of RNA substrate remaining after 3 minutes of incubation was <8% for the M41L/L210W/T215Y/R284K mutant RT, and 35% for WT and M41L/L210W/T215Y RTs. 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 141;194;136;189;153;147;200 146;199;140;193;158;152;205 RT;RT 166;206 168;209 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Furthermore, the strongest correlation involving R284K was found with T215Y (phi = 0.42; P < 2 x 10-5) (Additional file 1: Table S1). 2012 Retrovirology Result HIV R284K;T215Y 49;70 54;75 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Higher levels of significance were also detected for other pairs of TAMs, such as K70R and K219Q, D67N and K70R, and T215F and K219Q. 2012 Retrovirology Result HIV D67N;K219Q;K219Q;K70R;K70R;T215F 98;91;127;82;107;117 102;96;132;86;111;122 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. However, in the presence of AZT or tenofovir, this amino acid change produced a significant increase in the replication capacity of HIV-1 bearing mutations M41L, L210W and T215Y. 2012 Retrovirology Result HIV L210W;M41L;T215Y 162;156;172 167;160;177 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In the case of dATP incorporation, the catalytic efficiency (kcat/Km) of M41L/L210W/T215Y/R284K RT was also 2.6 times higher than the catalytic efficiency of the mutant M41L/L210W/T215Y. 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 78;174;73;169;90;84;180 83;179;77;173;95;89;185 RT 96 98 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In the presence of 3.2 mM ATP, we observed that with all NRTIs, the addition of R284K to a mutational background constituted by M41L, L210W and T215Y produced a significant increase in the amount of rescued and fully extended primers. 2012 Retrovirology Result HIV L210W;M41L;R284K;T215Y 134;128;80;144 139;132;85;149 NRTI 57 62 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In the presence of tenofovir, growth competition assays carried out in MT-4 cells failed to show significant differences between HIV-1 clones containing RT variants M41L/L210W/T215Y and M41L/L210W/T215Y/R284K (data not shown). 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 170;191;165;186;203;176;197 175;196;169;190;208;181;202 RT 153 155 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In the RT thumb subdomain, significant differences were found for R284K and V292I whose frequency was 3.8 and 1.9 times higher in the population failing HAART (P < 0.05). 2012 Retrovirology Result HIV R284K;V292I 66;76 71;81 RT 7 9 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In these experiments, M41L/L210W/T215Y and M41L/L210W/T215Y/R284K RTs showed nucleotide incorporation rates (kobs) of 21.5 +- 4.4 s-1 and 38.8 +- 9.4 s-1, respectively. 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 27;48;22;43;60;33;54 32;53;26;47;65;38;59 RT 66 69 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Interestingly, M41L/L210W/T215Y/R284K RT showed increased elongation rates compared with the M41L/L210W/T215Y RT in assays carried out with unblocked primers (Additional file 1: Figure S1). 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 20;98;15;93;32;26;104 25;103;19;97;37;31;109 RT;RT 38;110 40;112 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Interestingly, T69N appeared to be strongly correlated with K219Q (phi = 0.76, P = < 10-14) but also with K70R (phi = 0.50, P < 10-6). 2012 Retrovirology Result HIV K219Q;K70R;T69N 60;106;15 65;110;19 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K103N, Y181C and G190A) were also associated with therapy failure, all with P values below 5 x 10-4. 2012 Retrovirology Result HIV G190A;Y181C;K103N 17;7;0 22;12;5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. M41L and T215Y were also strongly correlated with V118I (P < 10-6), and with accessory mutations Q174R and L228H. 2012 Retrovirology Result HIV L228H;Q174R;T215Y;V118I;M41L 107;97;9;50;0 112;102;14;55;4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. M41L, D67N, L210W, T215F, etc....) and NNRTI resistance mutations (e.g. 2012 Retrovirology Result HIV D67N;L210W;T215F;M41L 6;12;19;0 10;17;24;4 NNRTI 39 44 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. M41L/L210W/T215Y/R284K RT showed a slightly higher processivity on heteropolymeric DNA substrates in comparison with the M41L/L210W/T215Y RT (Additional file 1: Figure S2). 2012 Retrovirology Result HIV L210W;L210W;M41L;R284K;T215Y;T215Y;M41L 5;126;121;17;11;132;0 10;131;125;22;16;137;4 RT;RT 23;138 25;140 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Mutants M41L/L210W/T215Y and M41L/L210W/T215Y/R284K grown in PBMCs in the absence of drugs showed decreased replication capacity compared to the WT virus (Figure 2). 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 13;34;8;29;46;19;40 18;39;12;33;51;24;45 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. No clustering was observed for the characteristic tenofovir resistance mutation K65R. 2012 Retrovirology Result HIV K65R 80 84 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. NRTI susceptibility and replication capacity of HIV-1 with RT mutations M41L, L210W, T215Y and R284K. 2012 Retrovirology Result HIV L210W;M41L;R284K;T215Y 78;72;95;85 83;76;100;90 NRTI;RT 0;59 4;61 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. On the other hand, as expected, WT and mutant R284K RTs showed much lower excision rates (<0.0034 min-1). 2012 Retrovirology Result HIV R284K 46 51 RT 52 55 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. On the other hand, R284K appears to have a minimal impact on AZTTP and tenofovir-DP binding, since the inhibition constants (Ki) obtained with WT and mutant RTs under our assay conditions were similar and around 2 to 3 muM (Table 3). 2012 Retrovirology Result HIV R284K 19 24 RT 157 160 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Our analysis showed that mutations A62V, Y181C, G190A, H208Y and T215F could cluster with the first group, although the association was weaker than for A98G, Q174R, I178L and L228H. 2012 Retrovirology Result HIV A62V;A98G;G190A;H208Y;I178L;L228H;Q174R;T215F;Y181C 35;152;48;55;165;175;158;65;41 39;156;53;60;170;180;163;70;46 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. R284K increases the DNA polymerization rate when combined with M41L, L210W and T215Y. 2012 Retrovirology Result HIV L210W;M41L;T215Y;R284K 69;63;79;0 74;67;84;5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. R284K was often identified in sequences containing one or more mutations of the TAM1 cluster, but lacking M184V. 2012 Retrovirology Result HIV M184V;R284K 106;0 111;5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. RNase H activity assays carried out with the RNA/DNA template-primer used in ATP-mediated rescue experiments demonstrated that the M41L/L210W/T215Y/R284K RT had increased endonucleolytic activity in comparison with M41L/L210W/T215Y RT (Figure 5). 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 136;220;131;215;148;142;226 141;225;135;219;153;147;231 RT;RT 154;232 156;234 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Steady-state kinetic parameters for dTTP and dATP incorporation showed that M41L/L210W/T215Y/R284K RT had an increased catalytic rate of nucleotide incorporation (kcat), in comparison with mutant M41L/L210W/T215Y and the WT enzyme (Table 3). 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 81;201;76;196;93;87;207 86;206;80;200;98;92;212 RT 99 101 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Taken together, those data suggest that R284K improves the rescue efficiency of M41L/L210W/T215Y RT by promoting dNTP incorporation, particularly in the presence of relatively high concentrations of nucleotide. 2012 Retrovirology Result HIV L210W;M41L;T215Y;R284K 85;80;91;40 90;84;96;45 RT 97 99 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. TAM1 pathway) (factor 2); and (3) D67N, K70R, T215F and K219Q. 2012 Retrovirology Result HIV K219Q;K70R;T215F 56;40;46 61;44;51 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The association between R284K and mutations of the TAM1 cluster was tested in the presence of drugs using recombinant HIV-1. 2012 Retrovirology Result HIV R284K 24 29 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The association of R284K with TAM1 mutations was consistent with previous reports demonstrating the higher prevalence of R284K in the NRTI-treated population. 2012 Retrovirology Result HIV R284K;R284K 19;121 24;126 NRTI 134 138 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The catalytic rate constants for RNA template cleavage obtained with the M41L/L210W/T215Y/R284K RT were around 2.5-3 times higher than those obtained with M41L/L210W/T215Y and WT RTs. 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 78;160;73;155;90;84;166 83;165;77;159;95;89;171 RT;RT 96;179 98;182 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The comparison of RT mutation frequencies in treated and naive populations revealed that M184V was strongly associated with virological failure (viral load above 1000 RNA copies/ml) (P < 2 x 10-14) (Table 1), although several TAMs (e.g. 2012 Retrovirology Result HIV M184V 89 94 RT 18 20 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The frequency of accessory mutations such as T39A, H208Y and L228H was also significantly higher in the treated population compared with the naive group. 2012 Retrovirology Result HIV H208Y;L228H;T39A 51;61;45 56;66;49 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The graphical representation of these three major factors revealed three clusters of mutations: (1) A98G, Q174R, I178L and L228H (factor 1); (2) M41L, L210W and T215Y. 2012 Retrovirology Result HIV I178L;L210W;L228H;Q174R;T215Y 113;151;123;106;161 118;156;128;111;166 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The mutant M41L/L210W/T215Y/R284K RT also showed increased RNase H activity in comparison with the WT enzyme, as demonstrated in assays carried out with RNA/DNA duplexes 38Trna/25PGA and 31Trna/21P (Figure 5). 2012 Retrovirology Result HIV L210W;M41L;R284K;T215Y 16;11;28;22 21;15;33;27 RT 34 36 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The presence of R284K did not affect ATP-mediated excision of any thymidine analogue. 2012 Retrovirology Result HIV R284K 16 21 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The R284K alone had no significant effect on the ATP-mediated rescuing ability of the WT RT. 2012 Retrovirology Result HIV R284K 4 9 RT 89 91 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The reduced stability of the RNA template in reactions catalyzed by M41L/L210W/T215Y/R284K RT is consistent with a reduction in the elongation efficiency of unblocked DNA primers in rescue assays. 2012 Retrovirology Result HIV L210W;M41L;R284K;T215Y 73;68;85;79 78;72;90;84 RT 91 93 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The results described above suggested that rescue efficiency differences between M41L/L210W/T215Y and M41L/L210W/T215Y/R284K RTs could originate from an altered DNA binding affinity. 2012 Retrovirology Result HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 86;107;81;102;119;92;113 91;112;85;106;124;97;118 RT 125 128 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The strongest correlations between mutations associated with therapy failure were found with TAMs M41L, L210W and T215Y, which form the TAM1 cluster (Additional file 1: Table S1). 2012 Retrovirology Result HIV L210W;M41L;T215Y 104;98;114 109;102;119 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. These results were consistent with an increase in the polymerization rate mediated by R284K when introduced in the context of TAM1 mutations. 2012 Retrovirology Result HIV R284K 86 91 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Thus, R284K had a compensatory effect on the loss of fitness caused by the TAM1 cluster of mutations, in the presence of NRTIs. 2012 Retrovirology Result HIV R284K 6 11 NRTI 121 126 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Under these conditions, phosphorolysis depending on ATP or PPi might be inhibited due to the formation of "dead-end complexes", and therefore the contribution of M41L, L210W and T215Y to tenofovir and d4T resistance was barely detectable. 2012 Retrovirology Result HIV L210W;M41L;T215Y 168;162;178 173;166;183 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Under these conditions, R284K had a detrimental effect on viral fitness. 2012 Retrovirology Result HIV R284K 24 29 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. WT and R284K RTs) also showed that the 284 mutation increased primer elongation, particularly when the concentrations of template-primer were not limiting (Additional file 1: Figure S1). 2012 Retrovirology Result HIV R284K 7 12 RT 13 16 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. 250nM), while Lys66Ala and Lys66Asn exhibit IC50s that are twice as high (559 and 563 respectively) resulting in a 3-fold decrease in susceptibility (Table 3). 2012 The FEBS journal Result HIV K66A;K66N 14;27 22;35 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. All of the enzymes tested (WT and Lys66 substitution mutants) efficiently inserted the correct nucleotide with similar efficiencies with the most impaired RT being Lys66Asn, leading to a ~3 times decrease in kcat/Km. 2012 The FEBS journal Result HIV K66N 164 172 RT 155 157 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Analysis of the IC50 values shows that the Lys65Ala mutant is the most susceptible to the inhibitor with an IC50 of 960nM (2-fold increase in susceptibility), while the Lys66 substitution mutants are more similar to the Lys65Arg mutant (Table 3). 2012 The FEBS journal Result HIV K65A;K65R 43;220 51;228 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Extension in the presence of 2',3'-Didehydro-3'-deoxy-thymidine-5'-triphosphate (d4TTP) shows once again that Lys66Arg allows for full length product extension similar to the WT enzyme (Supplementary Figures S2). 2012 The FEBS journal Result HIV K66R 110 118 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. For example, the kcat/Km values for incorporation of A opposite T and C opposite T were 0.200+-0.031 and 0.033+-0.013 for WT RT and 0.137+-0.030 and 0.005+-0.0043 for Lys66Ala mutant respectively. 2012 The FEBS journal Result HIV K66A 167 175 RT 125 127 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. However, in this instance the non-conservative mutants show an intermediate resistance profile when compared to WT and Lys65Arg (Supplementary Figures S2). 2012 The FEBS journal Result HIV K65R 119 127 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. In an attempt to study the role of Lys66 in drug susceptibility, qualitative gels, and quantitative filter-based drug resistance assays were performed using the various enzymes (WT, Lys66Arg, Lys66Ala, Lys66Asn, Lys66Thr, Lys65Ala and Lys65Arg) in the presence of 3 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). 2012 The FEBS journal Result HIV K65A;K65R;K66A;K66N;K66R;K66T 222;235;192;202;182;212 230;243;200;210;190;220 NNRTI;NRTI;NNRTI;NRTI 324;266;373;311 360;298;379;316 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. In contrast, the non-conservative substitution mutants specifically Lys66Ala and Lys66Asn allow for more full length product formation even at the highest concentration of AZTTP (4muM) (Supplementary Figures S2). 2012 The FEBS journal Result HIV K66A;K66N 68;81 76;89 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. In the presence of 3'-Azido-3'-Deoxythymidine-5 ' -Triphosphate (AZTTP), Lys66Arg and WT appear to have a similar resistance profile to the WT enzyme, as less full-length product is seen even at 1muM AZTTP (Supplementary Figures S2). 2012 The FEBS journal Result HIV K66R 73 81 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Interestingly, a conservative substitution at position 66 (Lys66Arg) affected the affinity of the enzyme for the matched t/p (6nM) and mismatched (8nM) 6- and 8-fold respectively, while a non-conservative Lys66Ala alteration had minimal effects. 2012 The FEBS journal Result HIV K66A;K66R 205;59 213;67 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Interestingly, in the presence of Tenofovir diphosphate (TFV-DP), even though the three non-conservative Lys66 substitutions exhibit slightly higher levels of full length product at the highest inhibitor concentration as compared to WT or Lys66Arg (Supplementary Figures S3), there does not appear to be a large difference in the IC50s obtained from the filter-based assays (Table 3). 2012 The FEBS journal Result HIV K66R 239 247 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Interestingly, WT, Lys66Arg, and Lys66Asn display increased G:T mispair catalytic efficiency (kcat/Km) compared to A:T. 2012 The FEBS journal Result HIV K66N;K66R 33;19 41;27 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Lastly, no apparent differences are observed for the WT, the Lys66 substitution mutants or the two Lys65 mutants in the presence of Efavirenz (EFV) with the exception of Lys65Ala. 2012 The FEBS journal Result HIV K65A 170 178 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Lys66Ala was used as a non-conservative substitution in addition to the three substitutions (Arg, Asn and Thr) observed in clinical isolates. 2012 The FEBS journal Result HIV K66A 0 8 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Representation of this data in terms of misinsertion efficiencies (fins) demonstrated that WT and Lys66Arg had a similar misinsertion fidelity, while the nonconservative substitutions at position 66 caused enhanced fidelity with an up to 23-fold reduction in misinsertion efficiency (Table 2). 2012 The FEBS journal Result HIV K66R 98 106 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. The data from these experiments shows that no difference in susceptibility is seen between the WT and Lys66Arg RTs (185nM vs. 2012 The FEBS journal Result HIV K66R 102 110 RT 111 114 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. The Lys66Ala effect is dramatic in this instance resulting in a 23-fold decrease in kcat/Km. 2012 The FEBS journal Result HIV K66A 4 12 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. The Lys66Arg substitution displayed a mismatch extension efficiency that was comparable to WT, whereas the reduction in fext for the non-conservative mutants (Lys66Ala, Lys66Asn, Lys66Thr) was 4-6-fold (Table 1B). 2012 The FEBS journal Result HIV K66A;K66N;K66R;K66T 159;169;4;179 167;177;12;187 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. To measure the kinetics of binding between the enzyme and the t/p substrate, we performed Surface Plasmon Resonance (SPR) experiments using the wild-type and four mutant RTs (Lys66Arg, Lys66Ala, Lys66Asn, and Lys66Thr) with matched or mismatched template/primers. 2012 The FEBS journal Result HIV K66A;K66N;K66R;K66T 185;195;175;209 193;203;183;217 RT 170 173 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Under conditions where a C:T mispair was formed, WT and Lys66Arg behaved similarly while the non-conservative mutants were severely impaired with a considerable increase seen in Km. 2012 The FEBS journal Result HIV K66R 56 64 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Under conditions where dGTP is inserted opposite a template T resulting in a G:T mispair, all of the enzymes show similar efficiencies of misinsertion except Lys66Ala. 2012 The FEBS journal Result HIV K66A 158 166 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Under conditions where the enzyme contains a Lys66Asn or Lys66Thr substitution at position 66, the affinity is decreased 5-49 fold for a matched and 10-32 fold for a mismatched t/p. 2012 The FEBS journal Result HIV K66N;K66T 45;57 53;65 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. When studying extension from matched terminus, the catalytic efficiency (kcat/Km) of extension was comparable for the WT and the Lys66Arg enzymes (Table 1A). 2012 The FEBS journal Result HIV K66R 129 137 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. While the non-conservative mutants (Lys66Ala, Lys66Asn and Lys66Thr) exhibited slightly lower extension efficiencies (up to 2-fold), the data suggests that substitutions at position 66 have a minimal effect on the efficiency of extension from a matched terminus (Table 1A). 2012 The FEBS journal Result HIV K66A;K66N;K66T 36;46;59 44;54;67 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. While WT and Lys66Arg retain the ability to misinsert dTTP complementary to a template thymidine base, the non-conservative substitution mutants are inept, resulting in a 6-8 fold reduction in misinsertion efficiency as compared to WT. 2012 The FEBS journal Result HIV K66R 13 21 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. Mutation I47V substitutes the shorter Val side chain and eliminates van der Waals contacts with adjacent residues, thus probably decreasing the stability of the hydrophobic cluster in PRI47V (Figure 2B). 2012 Biochemistry Result HIV I47V 9 13 PR 184 186 22963370 Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. These peptides are assumed to derive from very slow autoproteolysis, since the L63I substitution almost eliminates a site of autoproteolytic cleavage. 2012 Biochemistry Result HIV L63I 79 83 22970187 Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41. Site mutations in the coreceptor binding site, loop D or V5 also did not affect m43 binding to gp120, but site mutation in CD4bs (D368R) abolish m43 binding to gp120YU2. 2012 PloS one Result HIV D368R 130 135 gp120 95 100 22970187 Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41. We further measured the binding of IgG1 m43 to gp120JRFL V1, V2, V3 loop deletion mutants, and to four gp120yu2 site mutants with knock-out mutations in the CD4 binding site (D368R), the coreceptor binding site (I420R), loop D (N279E), and V5 loop (G459E) in comparison with CD4bs mAbs b12 and VRC01, CD4i mAb 17b, and V3 loop-specific mAb 39F. 2012 PloS one Result HIV D368R;G459E;I420R;N279E 175;249;212;228 180;254;217;233 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. According to the comments given by Stanford University HIV-1 Resistance Database, mutations V106M and Y181C can cause high level resistance to NVP, while mutations A98G and V108I just result in low-level reduction in susceptibility to NVP. 2012 PloS one Result HIV A98G;V106M;V108I;Y181C 164;92;173;102 168;97;178;107 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. After 25 passages of PBMC cultures in the presence of gradually increasing concentration of NVP, four combination profiles of mutations, which were initialed by three previously reported mutations A98G, V108I, Y181C, and reported mutations I135T together with a novel mutation I382L, were identified (Figure 4). 2012 PloS one Result HIV A98G;I135T;I382L;V108I;Y181C 197;240;277;203;210 201;245;282;208;215 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. All these mutations, including the pre-existing congenital NNRTI minor mutation V179E, persisted to the end of this in vitro study. 2012 PloS one Result HIV V179E 80 85 NNRTI 59 64 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Among 4 variants with the initial mutations A98G, V108I, Y181C, and I135T/I382L respectively, the variant with the mutation Y181C showed the highest resistance to NVP, which resulted in about 450 folds increase of NVP resistance. 2012 PloS one Result HIV A98G;I135T;I382L;V108I;Y181C;Y181C 44;68;74;50;57;124 48;73;79;55;62;129 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Among seven novel mutations, one (P4H) did not show any NVP resistant effect and the other 6 were associated with low level of NVP resistance. 2012 PloS one Result HIV P4H 34 37 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Among them, I178M appeared in four parallel cultures, while V106M was selected in three independent virus cultures together with I178M. 2012 PloS one Result HIV I178M;I178M;V106M 12;129;60 17;134;65 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Another mutation K238N alone is not a common mutation selected by NNRTI treatment and its effect on resistance to NVP is still unknown. 2012 PloS one Result HIV K238N 17 22 NNRTI 66 71 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. As summarized in Table 3, two reported mutations V106M and Y181C were characterized to be associated with high level of NVP resistance, while the other 5 known mutations A98G, K238N V108I, I135T and V189I were classified as medium or low level of NVP resistance. 2012 PloS one Result HIV A98G;I135T;K238N;V106M;V108I;V189I;Y181C 170;189;176;49;182;199;59 174;194;181;54;187;204;64 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Even in the combination of two mutations, I135T/I382I was associated with median level of NVP resistance but I178M/I382V only gave rise to low level of NVP resistance. 2012 PloS one Result HIV I135T;I178M;I382I;I382V 42;109;48;115 47;114;53;120 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. For example, initial or subsequent mutation V108I was associated with 3.5 or 3.1 folds increase of NVP resistance, while mutations V108I/T386A accounted for 5 folds increase of NVP resistance. 2012 PloS one Result HIV T386A;V108I;V108I 137;44;131 142;49;136 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Furthermore, drug resistant effect of K238N is reported to be unknown in the database, but it showed low level of drug resistance in this study. 2012 PloS one Result HIV K238N 38 43 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. In one of the parallel culture, the initial mutation V108I disappeared later in the subsequent selection cultures with higher concentration of NVP. 2012 PloS one Result HIV V108I 53 58 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. In the variants appeared subsequently in the presence of increasing concentrations of NVP, the variant with additional mutation V106M caused about 22-32 folds increase of NVP resistance, while the variants with additional mutations K238N/T48I/I178M and V108I/T386A showed about 5-10 folds increase of NVP resistance. 2012 PloS one Result HIV I178M;K238N;T48I;T386A;V106M;V108I 243;232;238;259;128;253 248;237;242;264;133;258 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. In these combination profiles, three previously reported mutations K238N, V106M, V189I, and 6 novel mutations T48I, I178M, T386A, V314A, I382V and P4H appeared gradually and formed combinations of up to 3-5 mutations at the end of the selection. 2012 PloS one Result HIV I178M;I382V;K238N;P4H;T386A;T48I;V106M;V189I;V314A 116;137;67;147;123;110;74;81;130 121;142;72;150;128;114;79;86;135 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Mutations V106M, V108I and Y181C in CRF07_BC were associated with similar NVP resistance as that reported in the database, but A98G in CRF07_BC might be related to higher NVP resistance than that reported in the database. 2012 PloS one Result HIV A98G;V106M;V108I;Y181C 127;10;17;27 131;15;22;32 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. No major or minor PR mutations and no NRTI mutations were found in CNGZD, but a NNRTI mutation V179E was detected, which was predicted to cause low-level resistance to NVP, efavirenz (EFV) and delavirdine (DLV) according to the comment of Stanford University HIV drug resistance database. 2012 PloS one Result HIV V179E 95 100 NNRTI;NRTI;PR 80;38;18 85;42;20 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Seven novel mutations P4H, T48I, I178M, V314A, I382L/V and T386A have not been reported to cause NVP resistance. 2012 PloS one Result HIV I178M;I382L;I382V;P4H;T386A;T48I;V314A 33;47;47;22;59;27;40 38;54;54;25;64;31;45 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Similarly, the variants with additional K238N/T48I/I178M, I178M/I382V and I135T/I382L resulted in about 10, 3.5 and 7.3 folds increase of NVP resistance, respectively. 2012 PloS one Result HIV I178M;K238N;T48I;I135T;I178M;I382L;I382V 51;40;46;74;58;80;64 56;45;50;79;63;85;69 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. The EC50 of NVP in the variants with the mutations A98G or two other mutations I135T/I382L increased for about 17 or 7 folds, while that in the variant with mutation V108I increased for less than 4 folds. 2012 PloS one Result HIV A98G;I135T;I382L;V108I 51;79;85;166 55;84;90;171 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. The NVP resistance of the variants with the other additional mutations V314A, V189I, I178M and I178M/I382V increased for less than 4 folds, but the mutation P4H was not related to NVP resistance. 2012 PloS one Result HIV I178M;I178M;I382V;P4H;V189I;V314A 85;95;101;157;78;71 90;100;106;160;83;76 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Therefore, the novel mutations I178M and I382L, and the reported mutation I135T would be associated with low level of NVP resistance (<4 folds increase). 2012 PloS one Result HIV I135T;I178M;I382L 74;31;41 79;36;46 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Thus, NVP resistance of the variant with mutation T386A alone should increase less than 4 folds as compared to wild type. 2012 PloS one Result HIV T386A 50 55 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. V108I was also found in three selected mutants as initial or non-initial mutation in our study. 2012 PloS one Result HIV V108I 0 5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. 5), and of these, 4 mutants (T257A, E370A, D474A and M475A) that had a difference of 10-fold or greater (before statistical analysis) were selected for further analysis. 2013 Proteins Result HIV D474A;E370A;M475A;T257A 43;36;53;29 48;41;58;34 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. 6E and F) and fitting a 1:1 Langmuir binding equation to these data points, we obtained an affinity of 239 +- 3 nM for D474A compared to 78 +- 2 for its WT control, which amounts to a 3-fold decrease in affinity for 17b IgG. 2013 Proteins Result HIV D474A 119 124 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. 6G), indicating that the affinity difference observed with 17b Fab for T257A is comparable to the affinity difference that would have been observed if IgG were used. 2013 Proteins Result HIV T257A 71 76 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Alternatively, M475A's resistance to inhibition of 17b binding by KR21 (only 4-fold higher IC50 compared to WT) may be caused by a global conformational change induced by this mutation, as its KD to 17b was also 3-fold higher than that of WT. 2013 Proteins Result HIV M475A 15 20 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Although I371A had a moderate effect (about 10-fold compared to WT) and V101A and R480A had smaller effects (less than 2-fold and 5-fold, respectively) on CD4 or 17b inhibition by the PTs, these effects were small and as there was no prior study to validate the importance of these mutations, these mutants were not carried over to the next phase of screening. 2013 Proteins Result HIV I371A;R480A;V101A 9;82;72 14;87;77 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Although the T257A mutation was previously observed to reduce CD4 binding roughly 30% in a pull-down assay using cell-lysates containing mutant full-length envelope protein, we observed much smaller differences in assays with our purified proteins, confirming that the overall CD4 binding site was not perturbed by these mutations. 2013 Proteins Result HIV T257A 13 18 Env 156 164 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. As 1 muM 17b Fab and 400 nM 17b IgG were observed to have the same IC50's for KR21 inhibition of binding to WT gp120 (within 10% of each other, not shown), thus 400 nM 17b IgG was used in the later assay with E370A and M475A in order to increase the signal from binding. 2013 Proteins Result HIV E370A;M475A 209;219 214;224 gp120 111 116 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. As with direct binding affinity, the tier 2 mutants E370A and M475A had a similar effect on CD4 inhibition in both the capture and direct immobilization assays. 2013 Proteins Result HIV E370A;M475A 52;62 57;67 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. At the time this experiment was done, the T257A surface had lost functionality and did not give measurable signals for 17b IgG binding. 2013 Proteins Result HIV T257A 42 47 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Comparing IC50s of KR21 for CD4 versus 17b, T257A and M475A mutations seem to affect 17b binding only half as much as they affect CD4 binding (fold difference with WT: 38 vs. 2013 Proteins Result HIV M475A;T257A 54;44 59;49 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. D474A also had a 3 +- 1 fold lower affinity for 17b Fab. 2013 Proteins Result HIV D474A 0 5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. E370A and M475A had 17b IgG affinities of 443 +- 42 and 316 +- 30 nM, respectively, compared to 93 +- 0.1 for their WT control, which amounted to affinity differences of 5 +- 0.5 and 3 +- 0.3 fold. 2013 Proteins Result HIV M475A;E370A 10;0 15;5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. E370A and M475A mutants had KR21 affinities of 386 +- 71 and 196 +- 34 nM, respectively, compared to 23 +- 8 for their WT control. 2013 Proteins Result HIV M475A;E370A 10;0 15;5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. E370A and M475A were also refractory to inhibition by CD4, with 10 and 12 times higher IC50s than WT, respectively. 2013 Proteins Result HIV M475A;E370A 10;0 15;5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. E370A had a CD4 IC50 for KR21 of 998 +- 68 nM and M475's was 686 +- 16 nM, which were 12 +- 1 and 8 +- 0.2 fold greater than that for WT, 70 +- 1 nM. 2013 Proteins Result HIV E370A 0 5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Experimental variation could be measured for V255A, E370A and M475A as repeat analysis was done with these mutants, and the experimental variation (standard deviation) was greater than the observed affinity difference with WT for V255A and M475A, but was less than the observed difference for E370A (affinity difference of 5 +- 3 fold, see table I). 2013 Proteins Result HIV E370A;E370A;M475A;M475A;V255A;V255A 52;293;62;240;45;230 57;298;67;245;50;235 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. For tier 1 mutants, IC50s calculated were 85 +- 6 nM for WT, 3.3 +- 0.1 muM for T257A and 4.3 +- 0.2 muM for D474A gp120. 2013 Proteins Result HIV D474A;T257A 109;80 114;85 gp120 115 120 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. However, the concentrations of 17b used were high (1 muM Fab for T257A and D474A and 400 nM IgG for E370A and M475A compared to 35 nM for CD4). 2013 Proteins Result HIV D474A;E370A;M475A;T257A 75;100;110;65 80;105;115;70 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. In comparison, those for E370A and M475A were 1.2 +- 0.2 muM and 422 +- 32 nM, compared to 87 +- 2 for WT, with differences of 10 +- 2 and 4 +- 0.4 fold, respectively. 2013 Proteins Result HIV E370A;M475A 25;35 30;40 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. K421A had a slightly faster off-rate that was balanced by a faster on-rate resulting in slightly lower (improved) dissociation constant (KD) than WT. 2013 Proteins Result HIV K421A 0 5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. KR21 IC50s for T257A and D474A binding to 17b Fab were 2 +- 0.1 and 6.2 +- 1.7 muM, compared to 110 +- 15 nM for WT, with a difference of 18 +- 1 and 56 +- 15 fold. 2013 Proteins Result HIV D474A;T257A 25;15 30;20 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. M475A, on the other hand, binds to KR21 only 8 +- 1.5 fold weaker than WT. 2013 Proteins Result HIV M475A 0 5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. M95A had a faster off-rate that was balanced by a faster on-rate resulting in no net change in KD. 2013 Proteins Result HIV M95A 0 4 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. M95A, K97A, E102A and V430A gp120 were essentially identical to WT in their binding kinetics for KR21-alphabt. 2013 Proteins Result HIV E102A;K97A;V430A;M95A 12;6;22;0 17;10;27;4 gp120 28 33 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. N98A, N99A, K120A, V121A, L122A, V372A and M426A were inhibited by UM24 or KR21 as well as WT and were not carried over to the next study. 2013 Proteins Result HIV K120A;L122A;M426A;N99A;V121A;V372A;N98A 12;26;43;6;19;33;0 17;31;48;10;24;38;4 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Of the remaining mutants, E370A's dissociation constant (KD) for KR21-alphabt was 5-fold higher than that of WT, while V255A, M475A and R476A's were 2, 4 and 3-fold higher, respectively (Table I). 2013 Proteins Result HIV E370A;M475A;R476A;V255A 26;126;136;119 31;131;141;124 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Of these mutants, the following were chosen for a more detailed screen of KR21's affinity and inhibitory potency on them: K97A, E102A and R476A since these mutations affected inhibition by the original peptide 12p1 and showed differences with WT in the ELISA screen. 2013 Proteins Result HIV E102A;K97A;R476A 128;122;138 133;126;143 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Results agreed with those from CD4 and 17 inhibition in that the T257A and D474A mutations conferred the highest resistance to KR21, resistance of E370A and M475A was moderate, and R476A conferred low resistance. 2013 Proteins Result HIV D474A;E370A;M475A;R476A;T257A 75;147;157;181;65 80;152;162;186;70 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. S2B); D474A and K421A since these mutants were shown to be important for peptide triazole function in later studies (not shown) and showed differences in the ELISA screen, E370A as this mutant was tested for the first time and showed a great difference with WT in the KR21 ELISA screen; T257A and M475A as these mutations had shown effects on antiviral potency (not shown) of the peptide triazole HNG-156 and also affected CD4 inhibition by KR21 in the ELISA screen; M95A was a mutant selected as a control for no effect (less than 2-fold) on PT activity. 2013 Proteins Result HIV D474A;E370A;K421A;M475A;M95A;T257A 6;172;16;297;467;287 11;177;21;302;471;292 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. S7C) and that containing WT, E370A and M475A gp120. 2013 Proteins Result HIV E370A;M475A 29;39 34;44 gp120 45 50 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Sample sensorgrams are given for the binding of KR21-alphabt to T257A, D474A, E370A and M475A gp120 in Figure 4. 2013 Proteins Result HIV D474A;E370A;M475A;T257A 71;78;88;64 76;83;93;69 gp120 94 99 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. T257A and D474A had 1.1 +- 0.3 and 1.3 +- 0.3 muM KDs to KR21 compared to 8 +- 2 nM for WT gp120. 2013 Proteins Result HIV D474A;T257A 10;0 15;5 gp120 91 96 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. T257A and D474A mutants were specifically disrupted in binding to KR21-alphabt. 2013 Proteins Result HIV D474A;T257A 10;0 15;5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The binding sensorgrams (average of duplicate injections) for the chip containing WT and D474A gp120. 2013 Proteins Result HIV D474A 89 94 gp120 95 100 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The decreased affinities of V430A and E370A to CD4 seen in the SPR screen (Table I), and here, respectively, may be caused by losses of direct contacts, as these residues make critical contacts with R59 and F43 of CD4, respectively. 2013 Proteins Result HIV E370A;V430A 38;28 43;33 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The differences seen with V255A, T257A, E370A, D474A, M475A and R476A were statistically significant. 2013 Proteins Result HIV D474A;E370A;M475A;R476A;T257A;V255A 47;40;54;64;33;26 52;45;59;69;38;31 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The fold differences in IC50 for T257A and D474A compared to WT (39 +- 1 and 51 +- 2, respectively) are comparable to those obtained using captured protein (33 +- 27 and 43 +- 1). 2013 Proteins Result HIV D474A;T257A 43;33 48;38 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The KD values for CD4 binding were 80 +- 3, 70 +- 2 and 90 +- 3 nM for WT, T257A and D474A, respectively. 2013 Proteins Result HIV D474A;T257A 85;75 90;80 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The most drastic change in KR21's ability to inhibit CD4 binding was seen with the weak binders T257A and D474A, which had 3088 and 4049 nM IC50s that are 33 and 43 fold higher than the 94 nM IC50 of WT gp120, respectively. 2013 Proteins Result HIV D474A;T257A 106;96 111;101 gp120 203 208 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The only mutation that possibly had a detrimental effect on CD4 binding (V430A, ca. 2013 Proteins Result HIV V430A 73 78 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The T257A and D474A inhibition assays were done with 1 muM 17b Fab instead of IgG to be free of avidity effects in our direct binding assays, however this was not enough to yield measurable off-rates. 2013 Proteins Result HIV D474A;T257A 14;4 19;9 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. The T257A and D474A mutants, which were classified as tier 1 in the capture assay, proved to have drastically lowered affinities to KR21. 2013 Proteins Result HIV D474A;T257A 14;4 19;9 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. These differences may be due to conformational changes in the protein, but do not explain the 130, 160 and 17-fold affinity differences observed for KR21 binding to T257A, D474A and E370A. 2013 Proteins Result HIV D474A;E370A;T257A 172;182;165 177;187;170 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. These values are statistically greater than the fold differences found with the mutants versus WT for CD4 binding, for which E370A had a 3 +- 0.1 fold lower affinity, while that of M475A was the same as WT. 2013 Proteins Result HIV E370A;M475A 125;181 130;186 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Thus, the effects of the mutations do not seem to differ for direct binding versus CD4/17b inhibition, except for a relatively larger increase in KDs compared to IC50s for T257A and D474A. 2013 Proteins Result HIV D474A;T257A 182;172 187;177 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. To validate the effects of the mutations first tested in the ELISA based inhibition assays and of two new mutants (V255A and V430A) that became available after the ELISA screen, we used an SPR based secondary screen to rank these mutants according to their binding affinity and inhibition by the biotinylated PT KR21. 2013 Proteins Result HIV V255A;V430A 115;125 121;130 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. V255A was not tested for viral inhibition. 2013 Proteins Result HIV V255A 0 5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. V255A, T257A, K421A and R476A had 3 to 6 fold greater IC50s. 2013 Proteins Result HIV K421A;R476A;T257A;V255A 14;24;7;0 19;29;12;5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. V430A did not differ from wild-type, as expected. 2013 Proteins Result HIV V430A 0 5 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. We tested the effect of the D474A, E370A and M475A mutations on 17b IgG binding. 2013 Proteins Result HIV D474A;E370A;M475A 28;35;45 33;40;50 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. While the KR21 affinity difference observed with purified E370A (17 +- 3) was barely statistically different than the differences observed with the V5-tag capture method and KR21-alphabt as the analyte (5 +- 3 fold), the assays did not give statistically different results for M475A (4 +- 5 fold vs. 2013 Proteins Result HIV E370A;M475A 58;277 63;282 23011758 HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. WT, T257A, E370A, D474A and M475A gp120YU2 were purified by 17b affinity and size exclusion as described in the Materials and Methods section under Production of wild type and mutant HIV-1YU2gp120. 2013 Proteins Result HIV D474A;E370A;M475A;T257A 18;11;28;4 23;16;33;9 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Breakthrough of NVP-resistant virus was generally observed one passage later with M184V mutant than with wild-type virus. 2012 Viruses Result HIV M184V 82 87 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. compared HIV wild-type to M184V mutant virus with three different stable doses of NVP in the absence of 3TC pressure. 2012 Viruses Result HIV M184V 26 31 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Figure 3 summarizes the selection of mutations prior to and after M184V-reversal, respectively. 2012 Viruses Result HIV M184V 66 71 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. In our experiments we confirmed that this additive 3TC-NNRTI effect is preserved even in the context of "real-life" patient isolates carrying the M184V "naturally", i.e., after in vivo exposure to 3TC. 2012 Viruses Result HIV M184V 146 151 NNRTI 55 60 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. In the NVP+3TC+ADV experiments, 3TC precluded M184V-reversal. 2012 Viruses Result HIV M184V 46 51 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Interestingly, E122K (#2/P11) and H208Y (#5/P3) would not be considered resistance mutations to ADV. 2012 Viruses Result HIV E122K;H208Y 15;34 20;39 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Interestingly, the mutations observed with ADV in our experiments were, with one exception (T69I), all positioned within the NNRTI binding pocket as opposed to the NRTI binding pocket. 2012 Viruses Result HIV T69I 92 96 NNRTI;NRTI 125;164 130;168 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. It seems plausible that structural constraints favor NNRTI mutations in positions 103-108 over changes in positions 181 or 188 as long as M184V predominates. 2012 Viruses Result HIV M184V 138 143 NNRTI 53 58 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. M184V reversion was promoted by ADV pressure only in the absence of 3TC pressure, contrary to reports of TDV+3TC serial passage experiments in SIV. 2012 Viruses Result HIV M184V 0 5 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. M184V-reversal was prevented by the addition of low-level 3TC in all cases despite an exponential increase in NVP doses of up to >2000-fold. 2012 Viruses Result HIV M184V 0 5 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Maintaining 3TC Pressure prevented M184V reversal in all instances. 2012 Viruses Result HIV M184V 35 40 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Mutations were selected at P2, P3, P5, and P6 without prior or simultaneous reversal at position 184 (M184V; left column). 2012 Viruses Result HIV M184V 102 107 Gag 43 45 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. No_drug simulates a treatment interruption and demonstrates that upon 3TC withdrawal, M184V tends to revert, even if the environment is stable. 2012 Viruses Result HIV M184V 86 91 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. NVP+3TC+ADV can be viewed as the 3TC with ADV+NVP, as NVP_only plus 3TC+ADV, or as ADV with NVP+3TC; 3TC again prevented M184V-reversal in all cases. 2012 Viruses Result HIV M184V 121 126 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. observed an additive effect of 3TC+NVP in enzymatic assays when measuring the amount of full-length RT product in M184V mutant virus. 2012 Viruses Result HIV M184V 114 119 RT 100 102 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Our contributions begin with the establishment of an in vitro system to study the impact of continued 3TC pressure on the selection of both M184V-reversal and resistance to NVP. 2012 Viruses Result HIV M184V 140 145 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Previous in vitro studies have shown that M184V may not delay the emergence of some protease inhibitors (PI) mutations, but of some PI and NNRTI. 2012 Viruses Result HIV M184V 42 47 PR;NNRTI;PI;PI 84;139;105;132 92;144;107;134 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Progression of Mutations with and without M184V Reversal. 2012 Viruses Result HIV M184V 42 47 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Several studies tested the decay of M184V during salvage therapy as well as treatment interruptions. 2012 Viruses Result HIV M184V 36 41 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. That is, no matter the genetic background, 3TC precluded M184V-reversal and impaired the selection of mutations in the NNRTI binding pocket. 2012 Viruses Result HIV M184V 57 62 NNRTI 119 124 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The addition of ADV to NVP_only (NVP+ADV) selects rapidly for M184V-reversal (P3). 2012 Viruses Result HIV M184V 62 67 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The authors suggested that 2.5-20 muM 3TC might exhibit a modest antiviral effect in M184V mutant virus despite high-level resistance. 2012 Viruses Result HIV M184V 85 90 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The average [NVP] was lower than in NVP_only for both M184V (left column, 24-fold versus 62-fold) and After M184V Reversal (right column: 682-fold versus 816-fold). 2012 Viruses Result HIV M184V;M184V 54;108 59;113 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The first new mutation with reversal (After M184V Reversal; right column) became prevalent at P7. 2012 Viruses Result HIV M184V 44 49 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The high degree of heterogeneity in the presence of ADV was independent of M184V-reversal, which was prevented by 3TC. 2012 Viruses Result HIV M184V 75 80 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The presence of low-dose (1muM) 3TC prevented reversal to wild-type from an M184V mutant background. 2012 Viruses Result HIV M184V 76 81 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The strategy is to preserve the resistance mutation M184V, which has been linked to an HIV-1 reverse transcriptase with altered biochemical properties. 2012 Viruses Result HIV M184V 52 57 RT 93 114 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The structure of M184I-HIV-1 has been solved and published, NNRTI have been co-crystallized with wild-type as well as Y181C and Y188L mutant RT. 2012 Viruses Result HIV M184I;Y181C;Y188L 17;118;128 22;123;133 NNRTI;RT 60;141 65;143 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. They also summarize counts of mutations together with incidence of V184M-reversal by isolate and passage number. 2012 Viruses Result HIV V184M 67 72 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Under extreme pressure (P12, 2048-fold NVP) we observe total numbers of 2x1, 2x2 and 1x3 mutations, but no M184V-reversal. 2012 Viruses Result HIV M184V 107 112 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. When all isolates in NVP_only are viewed together, we see the selection of wild-type at position 184 (M184V-reversal) in most (4/5) cases, though only one through the first six passages. 2012 Viruses Result HIV M184V 102 107 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Whenever 3TC was withdrawn, we selected for M184V-reversal, except for #4 in NVP_only (reversal at 215, 208, and 35 instead) and #1 in No_drug. 2012 Viruses Result HIV M184V 44 49 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. With NVP+3TC there was no M184V-reversal. 2012 Viruses Result HIV M184V 26 31 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. With NVP+ADV, mutations appeared after M184V-reversal, the first one at very low NVP concentration (P3; 4-fold). 2012 Viruses Result HIV M184V 39 44 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Although not statistically significant, EC50 values for the Y143C variant were 2-fold greater than wild-type in each of three independent experiments, potentially indicating low-level elvitegravir resistance. 2012 PloS one Result HIV Y143C 60 65 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Collectively, these data show that raltegravir-resistant mutants of HIV-2 are cross-resistant to elvitegravir and that substitutions T97A+143C, Q148K/R, G140S+Q148R and E92Q+N155H confer high-level elvitegravir resistance in HIV-2. 2012 PloS one Result HIV E92Q;G140S;N155H;Q148K;Q148R;Q148R;T97A 169;153;174;144;144;159;133 173;158;179;151;151;164;137 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Dose-response profiles for variants T97A, G140S and Q148H were similar to those obtained in parallel with wild-type ROD9 (Figure S1), resulting in mean EC50 values that were not significantly different from the parental strain (Figure 2A). 2012 PloS one Result HIV G140S;Q148H;T97A 42;52;36 47;57;40 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Importantly, two combinations of amino acid changes yielded greater-than-additive increases in the level of resistance to elvitegravir: T97A+Y143C (>200-fold; Figure 2C) and E92Q+N155H (51-fold; Figure 2C and 2D). 2012 PloS one Result HIV E92Q;N155H;T97A;Y143C 174;179;136;141 178;184;140;146 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. In contrast, replacements Q148K and Q148R alone were sufficient for a >50-fold increase in the EC50 for elvitegravir (Figure 2C). 2012 PloS one Result HIV Q148K;Q148R 26;36 31;41 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. In contrast, the infectious titers produced by E92Q+Y143C and T97A+Y143C ROD9 were comparable to or less than those of the Y143C clone (Figure 1), indicating that the E92Q and T97A replacements fail to compensate for the replication impairment imposed by the Y143C change. 2012 PloS one Result HIV E92Q;E92Q;T97A;T97A;Y143C;Y143C;Y143C;Y143C 47;167;62;176;52;67;123;259 51;171;66;180;57;72;128;264 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. In contrast, the Y143C, N155H, and Q148H, K, and R changes each conferred statistically-significant declines in infectious virus production, with mean titers 3-15-fold lower than that of wild-type ROD9 (Figure 1). 2012 PloS one Result HIV N155H;Q148H;Y143C 24;35;17 29;40;22 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. More substantial changes were conferred by Q148K, Q148R, N155H and T97A+N155H, which yielded moderate levels of resistance to the drug (7-15-fold; Figure 2A). 2012 PloS one Result HIV N155H;N155H;Q148K;Q148R;T97A 57;72;43;50;67 62;77;48;55;71 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Mutants E92Q, Y143C and T97A+Y143C showed statistically significant declines in raltegravir sensitivity, with mean EC50 values 3-4-fold greater than that of wild-type ROD9 (Figures 2A and S1). 2012 PloS one Result HIV E92Q;T97A;Y143C;Y143C 8;24;14;29 12;28;19;34 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Notably, the combination of G140S+Q148R resulted in improved replication capacity relative to Q148R alone; titers of the double-mutant were only 2-fold lower than wild type, versus a 15-fold reduction for the Q148R variant (Figure 1). 2012 PloS one Result HIV G140S;Q148R;Q148R;Q148R 28;34;94;209 33;39;99;214 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Similarly, variants E92Q, Y143C and N155H were 3- to 7-fold resistant to the drug, but the double mutants E92Q+Y143C and E92Q+N155H exhibited mean EC50 values 43- and 42-fold greater than wild-type ROD9, respectively (Figure 2A). 2012 PloS one Result HIV E92Q;E92Q;E92Q;N155H;N155H;Y143C;Y143C 20;106;121;36;126;26;111 24;110;125;41;131;31;116 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Slight improvements in infectivity were also noted for E92Q+N155H and T97A+N155H relative to N155H alone, although these differences were not statistically significant. 2012 PloS one Result HIV E92Q;N155H;N155H;N155H;T97A 55;60;75;93;70 59;65;80;98;74 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Substitutions T97A and G140S had no effect on elvitegravir susceptibility, whereas replacements E92Q, E92Q+Y143C, Q148H, N155H, and T97A+N155H imparted low to intermediate levels of resistance to the drug (mean EC50 values 3-13-fold greater than wild-type; Figure 2C). 2012 PloS one Result HIV E92Q;E92Q;G140S;N155H;N155H;Q148H;T97A;T97A;Y143C 96;102;23;121;137;114;14;132;107 100;106;28;126;142;119;18;136;112 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Taken together, these data show that replacements E92Q+Y143C, G140S+Q148R, and E92Q+N155H lead to high-level raltegravir resistance in HIV-2. 2012 PloS one Result HIV E92Q;E92Q;G140S;N155H;Q148R;Y143C 50;79;62;84;68;55 54;83;67;89;73;60 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. The combination of G140S+Q148R produced dose-response profiles similar to those of Q148R, although titers of the double mutant (expressed as % of no-drug controls) were consistently higher at 1000 nM elvitegravir, possibly reflecting a greater degree of resistance to the drug (Figure S1). 2012 PloS one Result HIV G140S;Q148R;Q148R 19;25;83 24;30;88 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. The G140S change alone produced no change in raltegravir susceptibility (Figure 2A), but the addition of G140S to the Q148R clone increased the level of raltegravir resistance from 15-fold (for Q148R alone) to >100-fold (for G140S+Q148R) (Figure 2B). 2012 PloS one Result HIV G140S;G140S;G140S;Q148R;Q148R;Q148R 4;105;225;118;194;231 9;110;230;123;199;236 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. The reductions in infectivity that were observed for Y143C, E92Q+Y143C, T97A+Y143C, Q148H/K/R, and N155H ROD9 were not attributable to differences in transfection efficiency, since comparable titers were obtained from two or more independent preparations of plasmid DNA for each wild-type or mutant construct (Figure 1). 2012 PloS one Result HIV E92Q;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143C;Y143C 60;99;84;84;84;72;53;65;77 64;104;93;93;93;76;58;70;82 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Variants E92Q, T97A, and G140S produced infectious titers that were comparable to wild-type (Figure 1). 2012 PloS one Result HIV E92Q;G140S;T97A 9;25;15 13;30;19 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. For PI-associated mutations, the minor mutation L10V and other polymorphism were detected. 2012 Diagnostic pathology Result HIV L10V 48 52 PI 4 6 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. The ART naive patients showed only NNRTI-associated mutations which were K103N (2 strains) and K101Q (1). 2012 Diagnostic pathology Result HIV K101Q;K103N 95;73 100;78 NNRTI 35 40 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. The minor PI mutation L10V was detected in one ART naive patient . 2012 Diagnostic pathology Result HIV L10V 22 26 PI 10 12 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. The NNRTI-associated mutations were K101Q (1), K103N (4), V179E (1), Y181C (1), Y188L (2), G190A (2) (Table 3). 2012 Diagnostic pathology Result HIV G190A;K101Q;K103N;V179E;Y181C;Y188L 91;36;47;58;69;80 96;41;52;63;74;85 NNRTI 4 9 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. The NRTI-associated mutations were D67N (2 strains), T69N (1), M184V (6), L210W (2), T215Y (2). 2012 Diagnostic pathology Result HIV D67N;L210W;M184V;T215Y;T69N 35;74;63;85;53 39;79;68;90;57 NRTI 4 8 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. At 83 days post-therapy, Q148R and N155H were detected in plasma and PBMC at 72% versus 33% and 12% versus 0% respectively. 2012 PloS one Result HIV N155H;Q148R 35;25 40;30 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. For example, in Subject 3180 on day 177 post-therapy, 77% of the plasma virus shared identical sequences and contained the G140S/Q148H mutations (Figure 2A, day 177 white shading), but the same sequence could only be found in 1% of the counterpart PBMC population. 2012 PloS one Result HIV G140S;Q148H 123;129 128;134 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. In contrast, prevalence of plasma DRMs increased rapidly to 69% (Q148H and G140S) 54 days post-therapy. 2012 PloS one Result HIV G140S;Q148H 75;65 80;71 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Note 115 days later, the prevalence of Q148R and N155H in both compartments dropped to 0% while Y143R took over and reached 100% in plasma yet remained at 0% in PBMCs. 2012 PloS one Result HIV N155H;Q148R;Y143R 49;39;96 54;44;101 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Note, however, that in subject 3180, the prevalence of Q148H and G140S in PBMC increased from 1% to 6% while the plasma prevalence decreased from 100% to 69%. 2012 PloS one Result HIV G140S;Q148H 65;55 70;60 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. The same trend for discordance was observed in secondary raltegravir-associated mutations T97A, E138A/K, S147G, V151I, M154I and G163R (Table 2 and Table S2, individual DRMs; Table S3, linked DRMs). 2012 PloS one Result HIV E138A;E138K;G163R;M154I;S147G;T97A;V151I 96;96;129;119;105;90;112 103;103;134;124;110;94;117 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Additionally, the mutation D67N was incorporated after 77 days (1 microM), when the VL rebounded to original levels before the drug selection. 2012 PloS one Result HIV D67N 27 31 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Contrasting to previous results observed in RTB, we could not find the multi-drug resistance mutation Q151M in the early stages of the selection process (figure 1B and Table 2). 2012 PloS one Result HIV Q151M 102 107 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. However, M184V was selected slight faster in RTC' than RTB'. 2012 PloS one Result HIV M184V 9 14 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Interestingly, subtype C followed a different route: it accumulated D67N after 77 days (1 microM) before rebounding and K70R after 84 days (2 microM) during the rebound process. 2012 PloS one Result HIV D67N;K70R 68;120 72;124 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Mutation M184I appeared between 50-56 days (~5-10 microM) of the selective process and was substituted by M184V or M184M/I/V at later passages with higher concentration of 3TC. 2012 PloS one Result HIV M184I;M184I;M184M;M184V;M184V 115;9;115;115;106 124;14;124;124;111 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Nevertheless, the final resistance profile was the same in all replicates: D67D/N, T215Y, F214L (Table 2). 2012 PloS one Result HIV D67D;D67N;F214L;T215Y 75;75;90;83 81;81;95;88 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The first mutation (D67N) was replaced by T215I at day 91 (2 microM), after the virus reached a VL level comparable to that before selection. 2012 PloS one Result HIV D67N;T215I 20;42 24;47 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The kinetics of M184I acquisition was similar for both RT clones. 2012 PloS one Result HIV M184I 16 21 RT 55 57 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The mutation D67N emerged before T215Y and F214L in some RTB' replicates; however, in other RTB' replicates D67N was selected after T215Y and F214L. 2012 PloS one Result HIV D67N;D67N;F214L;F214L;T215Y;T215Y 13;108;43;142;33;132 17;112;48;147;38;137 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The mutation Q151M was detected in subtype B clones after 63 days (0.256 microM), right after rebounding. 2012 PloS one Result HIV Q151M 13 18 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The mutation T215I (ATY or ATC) is an intermediary mutation between T215 (ACC) and T215F (TTT). 2012 PloS one Result HIV T215F;T215I 83;13 88;18 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The only exception in the mutational profiles was the selection of the non-polymorphic mutation E203K in one replicate of clone RTC' (Table 2). 2012 PloS one Result HIV E203K 96 101 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The rebound in 3TC selection was related to the appearance of a unique mutation M184I after 56 days (2.4 microM) regardless the subtype analyzed. 2012 PloS one Result HIV M184I 80 85 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Three final resistance profiles were detected in RTC' replicates: D67N, K70R and T215I (66,6%) or T215F (16,6%) or T215I/F (16,6%).The first mutations selected differ between replicates in RTB' passages (Table 3). 2012 PloS one Result HIV D67N;K70R;T215F;T215F;T215I;T215I 66;72;98;115;81;115 70;76;103;122;86;122 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. While RTC' replicates accumulated TAM 2 pathway (K70R and T215F or T215I), RTB' replicates followed TAM 1 mutations profile represented by T215Y. 2012 PloS one Result HIV K70R;T215F;T215I;T215Y 49;58;67;139 54;63;72;144 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. All patients received AZT and 3TC treatment, and the inclusion of 3TC resulted in the selection of the M184V mutation. 2013 Virology Result HIV M184V 103 108 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Database analysis showed A400T to be a common polymorphism in subtype C, while N348I (15%) and A371V (14%) were positively associated with RTI treatment. 2013 Virology Result HIV A371V;A400T;N348I 95;25;79 100;30;84 RT 139 142 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Even more impressive are the results with the triple POL mutant containing L100I + K103N + Y181C: all four patients' CNs could still enhance resistance 6 to 25-fold above the background ETR resistance (40x). 2013 Virology Result HIV K103N;L100I;Y181C 83;75;91 88;80;96 Pol 53 56 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Even though P2 and P3 contain N348I and A369V, CN mutations previously shown to potently increase AZT resistance in a WT pol background (2-5 fold and 9 fold, respectively), their resistance levels were still lower than P1 in the presence of TAMs. 2013 Virology Result HIV A369V;N348I 40;30 45;35 Pol 121 124 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. For the most recently approved potent NNRTI ETR, the patient CNs were still able to enhance resistance in the background of single POL mutants, except for K103N which is not a resistance mutation for ETR. 2013 Virology Result HIV K103N 155 160 NNRTI;Pol 38;131 43;134 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. G190A is not normally associated with DLV resistance, so only small increases in resistance were observed with the addition of CNs from P2, P3 and P5 (2-3x); however P1 did exhibit a modest 6x increase above reference background (C-G190A, 1.4x). 2013 Virology Result HIV G190A;G190A 232;0 237;5 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. However, the resistance profile for patient P1 is likely more complex and cannot be explained by the effect of M184V alone, as patients P2, P3 and P5 also contained M184V and exhibited increases in AZT resistance. 2013 Virology Result HIV M184V;M184V 111;165 116;170 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Inherent levels of AZT resistance were first tested for wild-type subtype C in the absence (C-WT) or presence (C-TAMs) of TAMs (D67N, K70R, T215F/Y and K219Q). 2013 Virology Result HIV D67N;K219Q;K70R;T215F;T215Y 128;152;134;140;140 132;157;138;147;147 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Interestingly, Q334D and G335D were negatively associated with treatment (Q334D: 11% naive vs. 2013 Virology Result HIV G335D;Q334D;Q334D 25;15;74 30;20;79 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Interestingly, the CN mutations observed in the subtype-C-infected treatment-experienced patients were similar to those previously identified in subtype B: P2, G335D and N348I; P3, Q334D, A371V, A376S, and A400T; and P5, G335D and A371V. 2013 Virology Result HIV A371V;A371V;A376S;A400T;G335D;G335D;N348I;Q334D 188;231;195;206;160;221;170;181 193;236;200;211;165;226;175;186 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Mutation Q334D, G335D, N348I, and A371V were found to be significantly associated with subtype-C-infected treatment-experienced patients. 2013 Virology Result HIV A371V;G335D;N348I;Q334D 34;16;23;9 39;21;28;14 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. P1 CN however was able to increase resistance 3-fold over the K103N background for ETR. 2013 Virology Result HIV K103N 62 67 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. P3 and P5 also received EFV treatment, which was associated with the selection of the NNRTI POL mutations L100I and K103N. 2013 Virology Result HIV K103N;L100I 116;106 121;111 NNRTI;Pol 86;92 91;95 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Since mutations in POL, especially L74V and M184V, can counteract AZT resistance levels, additional vectors were created in which the patient CNs were subcloned into pHL[C-TAMs]. 2013 Virology Result HIV L74V;M184V 35;44 39;49 Pol 19 22 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Since TAMs are not normally selected for in response to NNRTIs, NNRTI resistance associated with each patient CN was further evaluated by constructing vectors in which the patients CN was paired with a subtype-C POL domain containing mutations that increase NNRTI resistance, specifically either L100I, K103N, Y181C, G190A, or L100I + K103N + Y181C. 2013 Virology Result HIV G190A;K103N;K103N;L100I;L100I;Y181C;Y181C 317;303;335;296;327;310;343 322;308;340;301;332;315;348 NNRTI;NNRTI;NNRTI;Pol 56;64;258;212 62;69;263;215 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Slight increases in the AZT EC50 were observed between subtype B (18x) and C (28x) in the presence of TAMs, however this is likely due to the fact that the subtype B TAMs combination contained mutation T215Y instead of T215F. 2013 Virology Result HIV T215F;T215Y 219;202 224;207 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Standard TAMs (M41L, D67N, L210W, F214L, T215F/Y, K219N/E), were observed in POL, with P1 lacking NRTI TAMs. 2013 Virology Result HIV D67N;F214L;K219E;K219N;L210W;M41L;T215F;T215Y 21;34;50;50;27;15;41;41 25;39;57;57;32;19;48;48 NRTI;Pol 98;77 102;80 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Subtype B patient P1 also contained previously identified CN mutations A376S and A400T. 2013 Virology Result HIV A376S;A400T 71;81 76;86 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. The role of the A400T polymorphism in subtype C was also investigated, as it was previously shown that this same CN polymorphism in CRF01_AE played a significant role in AZT resistance; the T400A revertant mutant reduced AZT resistance 11-fold in wild-type CRF01_AE. 2013 Virology Result HIV A400T;T400A 16;190 21;195 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. This result likely shows the power of the M184V mutation in POL to counteract AZT resistance, as previously reported. 2013 Virology Result HIV M184V 42 47 Pol 60 63 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. This was in agreement with the observation that A400T has a similar prevalence in treatment-naive and RTI treated subtype C-infected patients, 61% and 67%, respectively (Table 1). 2013 Virology Result HIV A400T 48 53 RT 102 105 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Thus the 28-fold increase in resistance for C-TAMs versus the 18-fold increase in resistance for B-TAMs is likely due to the T215F amino acid change (resulting increase also 1.6-fold). 2013 Virology Result HIV T215F 125 130 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. We have previously shown that the difference in AZT resistance between TAMs combination D67N, K70R, T215Y and K219Q versus D67N, K70R, T215F and K219Q in a subtype B background is ~1.6-fold. 2013 Virology Result HIV D67N;D67N;K219Q;K219Q;K70R;K70R;T215F;T215Y 88;123;110;145;94;129;135;100 92;127;115;150;98;133;140;105 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. As expected from our biochemical data, the G140S-Q148H mutant caused a large increase in the EC50 values for RAL and XZ-259 to 1.7 and 6.8 muM, respectively (Table 1). 2013 ACS chemical biology Result HIV G140S;Q148H 43;49 48;54 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. As expected, the Y143R mutation had minimal impact on the activity of our five derivatives (less than 2.5-fold) whereas it induced a loss of sensitivity to RAL (37-fold increase in IC50) (Figure 1B). 2013 ACS chemical biology Result HIV Y143R 17 22 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Because the Y143R mutant has only minimal effect on the activity of XZ-259, it seems that the additional interactions enabled with the dimethyl sulfonamide are conserved in this arginine mutant. 2013 ACS chemical biology Result HIV Y143R 12 17 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Consequently, XZ-259 is over 10-time more potent than RAL at inhibiting the Y143R mutant virus. 2013 ACS chemical biology Result HIV Y143R 76 81 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Consistent with our biochemical assays, the Y143R mutation had minimal effect on the antiviral potency of our dihydro-1H-isoindole series (including XZ-259) with less than 2-fold increase in EC50 values. 2013 ACS chemical biology Result HIV Y143R 44 49 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. However, both conformations predicted modest (2- to 8-fold) increases in IC50 against the Y143R and N155H mutants and a greater increase (15- to 225-fold) against the G140S-Q148H mutant. 2013 ACS chemical biology Result HIV G140S;N155H;Q148H;Y143R 167;100;173;90 172;105;178;95 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. However, these derivatives are weak antiviral inhibitors and, in the context of the G140S-Q148H mutant, are at least 2-fold less potent than RAL. 2013 ACS chemical biology Result HIV G140S;Q148H 84;90 89;95 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. In contrast, the N155H mutation causes a 10-fold reduction in susceptibility to RAL. 2013 ACS chemical biology Result HIV N155H 17 22 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. In the context of the N155H and G140S-Q148H mutants, several EC50 values calculated were in the range of the CC50 (e.g. 2013 ACS chemical biology Result HIV G140S;N155H;Q148H 32;22;38 37;27;43 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. It also overcomes the Y143R mutation but not the N155H and G140S-Q148H mutations. 2013 ACS chemical biology Result HIV G140S;N155H;Q148H;Y143R 59;49;65;22 64;54;70;27 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. It retains potency against the RAL-resistant Y143R mutant and partial efficacy against the N155H mutant. 2013 ACS chemical biology Result HIV N155H;Y143R 91;45 96;50 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. The dihydro-1H-isoindole derivatives were tested against a panel of recombinant INs carrying mutations Y143R, N155H or G140S-Q148H that are known to cause RAL-resistance. 2013 ACS chemical biology Result HIV G140S;N155H;Q148H;Y143R 119;110;125;103 124;115;130;108 IN 80 83 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. The double mutation G140S-Q148H resulted in high resistance to XZ-90 and XZ-116 (up to 50-fold increase in ST IC50, Table 1). 2013 ACS chemical biology Result HIV G140S;Q148H 20;26 25;31 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. The entire series showed only a modest susceptibility to the N155H mutation, with a 3- to 4-fold increase in ST IC50 values compared to WT (Table 1). 2013 ACS chemical biology Result HIV N155H 61 66 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. The G140S-Q148H mutant induced resistance to the new derivative XZ-259 with a 57-fold increase in IC50 (Table 1). 2013 ACS chemical biology Result HIV G140S;Q148H 4;10 9;15 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. The N155H mutant was similarly susceptible than the WT virus to inhibition by XZ-90 and XZ-116 (less than 3-fold increase in EC50). 2013 ACS chemical biology Result HIV N155H 4 9 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. These results match the observed fold changes of 2.6 (Y143R), 3.9 (N155H) and 57 (G140S-Q148H) in the biochemical assays. 2013 ACS chemical biology Result HIV G140S;N155H;Q148H;Y143R 82;67;88;54 87;72;93;59 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Thus, in the biochemical assays with recombinant IN, XZ-259 is more potent than RAL against the N155H mutant, with an IC50 value of 300 nM versus 720 nM, respectively (Table 1 and Figure 1B). 2013 ACS chemical biology Result HIV N155H 96 101 IN 49 51 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Thus, the introduction of a dimethyl sulfonamide greatly improved the potency of the compounds against the WT enzyme but only partially increased the potency against the G140S-Q148H double mutant. 2013 ACS chemical biology Result HIV G140S;Q148H 170;176 175;181 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Thus, XZ-259 is 3-time less potent than RAL against the N155H mutant virus but still remains at least 2-time more potent than our previous compounds (Table 1). 2013 ACS chemical biology Result HIV N155H 56 61 23075516 Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase. Yet, XZ-259 inhibits the N155H mutant less potently than DTG or MK-0536. 2013 ACS chemical biology Result HIV N155H 25 30 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. D67N and K219E were the TAMs seen with K65R in the three patients who had both. 2013 AIDS (London, England) Result HIV K219E;K65R;D67N 9;39;0 14;43;4 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. M184V was the only mutation that was associated with a lower average HIV-1 RNA viral load (4.7 vs. 2013 AIDS (London, England) Result HIV M184V 0 5 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Most (90%) patients harbored the M184V/I mutation and 14% had the K65R mutation. 2013 AIDS (London, England) Result HIV K65R;M184I;M184V 66;33;33 70;40;40 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Patients on TDF based regimens were significantly more likely to have thymidine-sparing mutations (K65R (57%), M184I (30%), Y115F (13%)) as compared to AZT and d4T based regimens (p<=0.02). 2013 AIDS (London, England) Result HIV K65R;M184I;Y115F 99;111;124 104;116;129 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Secondary mutations related to polymorphisms (I13V (95%), M36I (83%), H69K (82%), V82I (43%) and L63P (28%)) also occurred among those genotyped. 2013 AIDS (London, England) Result HIV H69K;I13V;L63P;M36I;V82I 70;46;97;58;82 74;51;101;62;86 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. The L100I (36%), K103N (79%), and P225H (21%) mutations were more common in efavirenz based regimens as compared to nevirapine based regimens [Table 3]. 2013 AIDS (London, England) Result HIV K103N;L100I;P225H 17;4;34 22;9;39 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. The most frequent NNRTI mutations were Y181C/V (43%) and K103N (37%). 2013 AIDS (London, England) Result HIV K103N;Y181C;Y181V 57;39;39 62;46;46 NNRTI 18 23 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. The two patients on TDF based regimens with a TAM mutation (K219E) also had the K65R mutation. 2013 AIDS (London, England) Result HIV K219E;K65R 60;80 65;84 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Those who developed TAMs were more likely to be negative for the K65R mutation (70% vs. 2013 AIDS (London, England) Result HIV K65R 65 69 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Three patients had selected IAS PI major mutations (I50V, N83D, I84V and L90M). 2013 AIDS (London, England) Result HIV I50V;I84V;L90M;N83D 52;64;73;58 56;68;77;62 PI 32 34 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. 68/75 (91%) patients with discrepant efavirenz results harboured the V179D/E mutations (V179D (83%), V179E (17%)) compared to only 7/1226 (0.6%) of patients with no efavirenz discrepancy (p-value <0.001). 2012 BMC research notes Result HIV V179D;V179D;V179E;V179E 69;88;69;101 76;94;76;106 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. Although G190A/E and F227 were found in a proportion of these patients, a similar pattern to efavirenz could be seen whereby discrepant patients with V179D/E did not harbour any additional NNRTI RAMs. 2012 BMC research notes Result HIV G190A;G190E;V179D;V179E 9;9;150;150 16;16;157;157 NNRTI 189 194 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. Among the 1226 patients with no discrepancy, the efavirenz-associated mutations were A98G (0.3%), K103N (0.8%), K103S (0.2%), V106M (0.2%), V179D (0.6%), Y181C (0.6%), G190A (0.3%), G190E (0.1%), P225H (0.2%), F227C (0.1%) and K238T (0.1%). 2012 BMC research notes Result HIV A98G;F227C;G190A;G190E;K103N;K103S;K238T;P225H;V106M;V179D;Y181C 85;210;168;182;98;112;227;196;126;140;154 89;215;173;187;103;117;232;201;131;145;159 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. Apart from V179D/E, these 68 patients did not present any other efavirenz RAMs. 2012 BMC research notes Result HIV V179D;V179E 11;11 18;18 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. Of note, T39K, K43S, K122E, D123S, D177E, Q207A and R211S were the most common RT-mutations (86%) found in these 7 patients with respect to the reference wildtype virus. 2012 BMC research notes Result HIV D123S;D177E;K122E;K43S;Q207A;R211S;T39K 28;35;21;15;42;52;9 33;40;26;19;47;57;13 RT 79 81 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. RAMs found in discrepant patients for other NNRTIs were: etravirine (18 discordances): V179D (38.9%), V179E (11.1%), G190A (5.6%) and G190E (5.6%); nevirapine (12 discordances) V179D (75%); V179E (8.3%) and F227C (8.3%). 2012 BMC research notes Result HIV F227C;G190A;G190E;V179D;V179D;V179E;V179E 207;117;134;87;175;102;190 212;122;139;92;182;107;195 NNRTI 44 50 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Analysis of the data using this new model showed that T242N was 42% less fit than T/F (sij = -0.42 +- 0.03). 2012 Retrovirology Result HIV T242N 54 59 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. As a result, T242N was 37% less fit than NIA (sij = -0.37 +- 0.14). 2012 Retrovirology Result HIV T242N 13 18 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. At day 592, three mutations (T242N, V247I and G248A) in the B57/5801 restricted Gag240-249 epitope TSTLQEQIGW (TW10) were found in all detected viral genomes (Figure 1A). 2012 Retrovirology Result HIV G248A;T242N;V247I 46;29;36 51;34;41 Gag 80 83 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. At passage 1, T/F and T242N accounted for 73% and 27% of the viral population, respectively, although T242N was in nearly two fold excess in the inoculum (36% T/F and 64% T242N) (Figure 5A). 2012 Retrovirology Result HIV T242N;T242N;T242N 22;102;171 27;107;176 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. At passage 2, T/F (98%) almost completely replaced T242N and dominated in succeeding passages. 2012 Retrovirology Result HIV T242N 51 56 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. During four passages, NIA continuously increased in the viral population (from 74% to 91%) while T242N was gradually outcompeted (from 26% to 8%), although the proportion of each virus in the inoculum was similar (43% T242N and 57% NIA) (Figure 5B). 2012 Retrovirology Result HIV T242N;T242N 97;218 102;223 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. However, the number of passages required for T/F to dominate T242N was fewer than that previously observed, suggesting that the levels of fitness loss caused by the T242N mutation varies in different backbones. 2012 Retrovirology Result HIV T242N;T242N 61;165 66;170 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. However, when T242N was compared to T/F or NIA, the proportion of T242N in the culture decreased by two fold compared to that in the inoculum stock (Figure 3A and 3C), suggesting that T242N was less fit than both T/F and NIA. 2012 Retrovirology Result HIV T242N;T242N;T242N 14;66;185 19;71;190 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Importantly, no mutations at the I64T site were detected. 2012 Retrovirology Result HIV I64T 33 37 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. It was detected only 14 days after screening (first RNA positive sample) and was present together with a reversion mutation (I64T) in the tat/rev overlap region in the majority of the viral population. 2012 Retrovirology Result HIV I64T 125 129 Rev;Tat 142;138 145;141 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. NIA was different from T/F by three mutations (T242N, V247I and G248A) in the TW10 epitope. 2012 Retrovirology Result HIV G248A;T242N;V247I 64;47;54 69;52;59 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. R355K in the epitope Env352-369 in Env was the earliest CTL escape mutation. 2012 Retrovirology Result HIV R355K 0 5 Env;Env 21;35 24;38 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Sequence analysis showed 66% T/F, 30% NIA, 4% recombinant, and no T242N (Figure 6C and Figure 7). 2012 Retrovirology Result HIV T242N 66 71 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Since the fitness loss caused by the T242N mutation was better revealed after multiple rounds of passages , and discordant fitness results have been observed between single-passage and multiple-passage fitness assays , we sought to investigate whether the fitness cost caused by the T242N mutation in the T/F virus can be more accurately determined by repeatedly passaging the cell-free viruses to fresh CD4+ T cells. 2012 Retrovirology Result HIV T242N;T242N 37;283 42;288 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. T242N differed from the T/F virus by a single CTL escape mutation (T242N). 2012 Retrovirology Result HIV T242N;T242N 67;0 72;5 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Taken together, our results confirmed that the T242N mutation alone in the TW10 CTL epitope caused significant fitness loss in the multiple passage assay. 2012 Retrovirology Result HIV T242N 47 52 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The CTL escape mutation T242N has been reported to cause a significant fitness loss in vitro using the laboratory adapted NL4-3 virus backbone in several studies . 2012 Retrovirology Result HIV T242N 24 29 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The relative fitness of T242N was about 5% less fit than NIA (sij = -0.05 +- 0.04). 2012 Retrovirology Result HIV T242N 24 29 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The relative fitness of T242N was similar to that of T/F (sij = -0.009 +- 0.007). 2012 Retrovirology Result HIV T242N 24 29 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The V247I mutation was detected in the majority of the viral population at day 159, but it did not impact T cell recognition (Figure 1A and 1B). 2012 Retrovirology Result HIV V247I 4 9 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The virus (TK) with both R355K and I64T mutations was the predominant virus (53%) at day 14 and fixed at day 592 in the virus population (Figure 1C). 2012 Retrovirology Result HIV I64T;R355K 35;25 39;30 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. These results were very similar to what were identified among 596 viral genomes by PASS (62% T/F, 29% NIA, 9% recombinant, and no T242N). 2012 Retrovirology Result HIV T242N 130 135 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. This is at odds with the previous observation that a virus with the CTL escape mutation T242N was less fit than the WT virus . 2012 Retrovirology Result HIV T242N 88 93 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. This result is similar to that reported in a previous study , confirming that T242N mutation could cause a significant fitness loss in its cognate T/F virus backbone or in a NL4-3 backbone. 2012 Retrovirology Result HIV T242N 78 83 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. This strongly supports that the I64T recombinant detected in the co-culture of the T/F and TK viruses were indeed the results of recombination. 2012 Retrovirology Result HIV I64T 32 36 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Thus we could easily separate the recombinant from the three parental viruses by performing linkage analysis of two nucleosides at positions 242 and 247: 242T/247V (T/F), 242N/247V (T242N), 242N/247I (NIA), and 242T/247I (recombinant) (Figure 6A). 2012 Retrovirology Result HIV T242N 182 187 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. TK represented the predominant virus in vivo at day 14 and differed from T/F by two mutations (I64T and R355K). 2012 Retrovirology Result HIV I64T;R355K 95;104 100;109 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. TK was different from T/F by two mutations (I64T and R355K in Tat/Rev and Env, respectively) that were separated by 1258 bases. 2012 Retrovirology Result HIV I64T;R355K 44;53 49;58 Rev;Tat;Env 66;62;74 69;65;77 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. To determine if the I64T mutation was the result of reversion mutation during the multiple passages, we analyzed 51 3' half genome sequences obtained by SGA after 6 passages of the T/F virus. 2012 Retrovirology Result HIV I64T 20 24 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. To understand how those mutations affect viral fitness, we generated three infectious molecular clones (T242N, NIA and TK) by introducing mutations into the T/F viral genome (Figure 2A). 2012 Retrovirology Result HIV T242N 104 109 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Using the same linkage analysis, we analyzed both mutation sites and detected both possible recombinants (virus with only the I64T or R355K mutation) in 7.1% of the viral population at passage 1 (Figure 6D). 2012 Retrovirology Result HIV I64T;R355K 126;134 130;139 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. We first sought to investigate if the T242N mutation rendered the virus less fit than T/F in a single passage assay. 2012 Retrovirology Result HIV T242N 38 43 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. We infected the same CD4+ T cells with three viruses (T/F, T242N and NIA) and passaged the viruses six times. 2012 Retrovirology Result HIV T242N 59 64 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. When NIA and T242N were compared, the proportion of NIA accounted for the majority of the viral population at day 1 (85%) and slightly increased to 90% at day 3 (Figure 3C). 2012 Retrovirology Result HIV T242N 13 18 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. When T/F and T242N were compared, T/F predominated the viral population (70%) since day 1, However, the ratio between two viruses did not change throughout the culture (Figure 3A), although the number of viral genome exponentially increased in the culture media during the same period as shown in Figure 2B. 2012 Retrovirology Result HIV T242N 13 18 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. When T242N and NIA, which was naturally selected in vivo, were compared, NIA was also more fit than T242N. 2012 Retrovirology Result HIV T242N;T242N 5;100 10;105 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Although the WT, I50VPR, V82APR and I84VPR mutant trajectories have significant overlaps, some differences can still be observed (Figure 6a). 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 17;36;25 23;42;31 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Average distances for the WT-, I50VPR-, V82APR-, and I84VPR-SWCNT complexes are 6.55 A, 6.42 A, 6.79 A and 6.23 A, with SD 0.60 A, 0.40 A, 0.87 A and 0.35 A, respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 31;53;40 37;59;46 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Besides the mutation residue I50V/I50'V, Figure 12 and Table 3 show that Arg08 and Gly27' contributes to the binding decrease by over 1.0kcal/mol, which is basically consistent with the longer distance between the residue and the SWCNT as shown in Figures 13a. 2012 Journal of molecular graphics & modelling Result HIV I50V 29 33 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. By analyzing to the distribution plot for the TriCa-B angle (Figures 8b & 8d), it observed that the I50VPR, V82APR and I84VPR mutants also has wide overlapping as compared to the WT distribution. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 100;119;108 106;125;114 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Compared to the I50VPR, more residues indirectly contribute to the binding decrease for the V82APR. 2012 Journal of molecular graphics & modelling Result HIV I50V;V82A 16;92 22;98 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Conversely, the inter-flap H-bonds seems to be poor in all complexes except for I50VPR and V82APR, where the percentage is 8.32 and 7.90 respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V;V82A 80;91 86;97 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Figures 13c and 13d show a comparison of the C-C distances for the selected residues from flaps, active site and active site wall regions of the WT and mutant V82APR. 2012 Journal of molecular graphics & modelling Result HIV V82A 159 165 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. First, the I84VPR mutant has clearly different values than the WT, I50VPR and is partly overlapped with the V82APR mutant at around 6 ns and 8.0 to 10 ns. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 67;11;108 73;17;114 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. For all of three mutants their bindings to the SWCNT show decrease to different extent, and as compared to the WT complex the binding energies decrease by 5.97, 14.20, and 22.63 kcal/mol for the I50V, V82APR and I84VPR mutants, respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 195;212;201 199;218;207 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. For mutant I50VPR, the mean and SD are 96.41 and 5.61 , respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V 11 17 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. For the I50VPR, the decrease of binding energy by 5.97 kcal/mol partially attributes to the loss of one CH3 group from Ile50/Ile50' (DeltaG: -4.07/-3.47 kcal/mol) to Val50/Val50' (-3.41/-3.33 kcal/mol) in the I50V mutant flap tip region (Figure 12 and Table 3), which accounts approximately 12% of the total binding loss. 2012 Journal of molecular graphics & modelling Result HIV I50V;I50V 8;209 14;213 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. For the V82APR and I84VPR mutants DeltaEvdw shows a similar, yet significant decrease by 5.1 and 23.8 kcal/mol respectively, which are dominantly responsible for the decrease in binding affinities. 2012 Journal of molecular graphics & modelling Result HIV I84V;V82A 19;8 25;14 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. However, it is surprised to find that polar solvation energy becomes less than that of the WTPR (DeltaGPB 23.5 vs 32.4 kcal/mol), indicating an increase of hydrophobicity for I84VPR. 2012 Journal of molecular graphics & modelling Result HIV I84V 175 181 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. However, it was found that there only a single peak exists for all complexes except the I84VPR complex, where there exist 2-3 different peaks suggesting a different range of conformations for the said angle. 2012 Journal of molecular graphics & modelling Result HIV I84V 88 94 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. However, solvation of the V82APR is much stronger than that of the I84VPR (DeltaGpb, 35.7 vs 23.5 kcal/mol). 2012 Journal of molecular graphics & modelling Result HIV I84V;V82A 67;26 73;32 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. However, the I84VPR mutant has lower values in the first 13 ns and is partially overlapped with the other mutants, after which it jumps to a higher range where it remain overlapped with all other complexes. 2012 Journal of molecular graphics & modelling Result HIV I84V 13 19 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. In order to get insights into the different contributions to the binding of the SWCNT to WT, I50VPR,V82APR and I84VPR mutant, absolute binding free energies are calculated for all the complexes using the MM-PBSA method. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 93;111;100 99;117;106 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. In the I50VPR mutant the residue Asp29 has a net increase in the binding affinity by approximately -2.0 kcal/mol, which was well supported by the distance variation between the SWCNT and Asp29 from the WT (8.8A) to the I50VPR mutant (4.5A) in Figure 13b. 2012 Journal of molecular graphics & modelling Result HIV I50V;I50V 7;219 13;225 Asp;Asp 33;187 36;190 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. In the I84VPR mutant the mutated residues Val84 (1.6 kcal/mol) and Val84' (1.2 kcal/mol) have direct effect on the loss of binding affinities. 2012 Journal of molecular graphics & modelling Result HIV I84V 7 13 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. It is noted that, the change from WT to mutant type of the HIV-pr has not affected much on the intra-flap H-bonding pattern, which can be seen with occupancy of (~ 90% in I50VPR and I84VPR) and (>= 90% in WT and V82APR mutants). 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 171;182;212 177;188;218 PR 63 65 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. It was noted that residues in the active site region (Pro81) in the I84VPR mutant and cantilever region (Gln61') in the V82APR mutant have significant fluctuations as compared to the WT counterpart. 2012 Journal of molecular graphics & modelling Result HIV I84V;V82A 68;120 74;126 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Moreover, the I84VPR mutant trajectory has always a higher value in the range of 16-20 A. 2012 Journal of molecular graphics & modelling Result HIV I84V 14 20 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Second, the WT and V82APR mutant have two and three phase increment. 2012 Journal of molecular graphics & modelling Result HIV V82A 19 25 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The average RMSF values per-residue in the flap and active-site binding region for the WT-, I50VPR-, V82APR- and I84VPR- SWCNT complexes are 1.04, 0.97, 1.05 and 1.14 A, respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 92;113;101 98;119;107 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The binding free energies of WT, I50VPR, V82APR and I84VPR complexes are -70.85, -64.88, -56.65 and -48.22 kcal/mol, respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 33;52;41 39;58;47 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The decrease is consistent with the C...C distance increase for Val50-SWCNT from 3.5A to 3.6A in chain-B and from 3.6 to 3.8A in chain-A, due to the I50V and I'50V', shown in Figures 13(a) and 13(b) suggesting a direct loss of the vdw binding affinity. 2012 Journal of molecular graphics & modelling Result HIV I50V 149 153 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The fluctuation of SWCNT in I84VPR active site is more than WT, I50VPR and V82APR, which may be due to the larger active site volume. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 64;28;75 70;34;81 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The I50VPR mutation shows a binding decrease due to DeltaEvdw by about 1.1 kcal/mol, DeltaEele by 1.13 kcal/mol, DeltaGpb by 1.02 kcal/mol, and -DeltaTS by 1.96 kcal/mol relative to the WT. 2012 Journal of molecular graphics & modelling Result HIV I50V 4 10 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The larger active site-flap distance for I84VPR mutants makes the active site cavity more spacious as compared to the WT. 2012 Journal of molecular graphics & modelling Result HIV I84V 41 47 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The mean and SD of WT (I50VPR) are 13.81 (15.32) A and 0.58 (0.45) A, respectively; whereas for the mutant V82APR (I84VPR), the mean and SD are 15.51 (17.22) and 0.93 (0.80) A, respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 23;115;107 29;121;113 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The mean and SD of WT (I50VPR) are 15.24 (14.64) A and SD is 0.48 (0.66) A, respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V 23 29 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The mean for the SWCNT-Asp25 distance in WT-SWCNT complex is 8.03A, for I50VPR-SWCNT is 8.94A, for V82APR-SWCNT complex is 8.92A and for I84VPR-SWCNT complex is 10.42 A with their respective standard deviation (SD) of 0.89A, 0.63A 0.99A and 0.83 A. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 72;137;99 78;143;105 Asp 23 26 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The mean of I50VPR, V82APR and I84VPR are 113.07 , 111.24 and 110.89 and SD are 7.01 , 7.38 and 7.16 respectively. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 12;31;20 18;37;26 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The mean of the distribution for I84VPR is larger by 3.41 A than WT, 1.90 A than I50VPR and 1.71 A than V82APR. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 81;33;104 87;39;110 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The mobility of the residues in the flap elbow regions of the two chains are almost overlapped for WT and all the mutant complexes; however, the flap tips residues Phe53 and Phe53' in the V82APR mutant have a comparatively higher fluctuations than in the WT, I50VPR and I84VPR mutants. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 259;270;188 265;276;194 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The RMSD plots indicate that the conformations of the WT, I50VPR, V82APR and I84VPR mutant HIV-1-PR complexes are in good equilibrium. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 58;77;66 64;83;72 PR 97 99 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The time-series plot shows that, the four systems have almost overlapped distances with few exceptions near 7ns in case of I84VPR, from around 8.0ns to 13.0 ns for V82APR and the last 2 ns in case of WT, where the distance goes up to a range of 6-9A. 2012 Journal of molecular graphics & modelling Result HIV I84V;V82A 123;164 129;170 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The trajectory of the I84VPR/SWCNT complex fluctuates more than other three trajectories at around 18-19 ns, after that it goes parallel to others. 2012 Journal of molecular graphics & modelling Result HIV I84V 22 26 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The TriCa-A (Gly49-Ile50-Gly51)Calpha in chain-A and TriCa-B (Gly49'-Ile50'-Gly51')Calpha angles in chain-B in the flap tip region for all four WT, I50VPR, V82APR and I84VPR complexes were also analyzed. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 148;167;156 154;173;162 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The V82APR trajectory then continues at a higher range and from 12 ns onwards goes overlapped with I50VPR. 2012 Journal of molecular graphics & modelling Result HIV I50V;V82A 99;4 105;10 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The WT distribution is quite different as compared to the mutant structures, where I50VPR and V82APR mutant partially overlapped and is clearly different from WT. 2012 Journal of molecular graphics & modelling Result HIV I50V;V82A 83;94 89;100 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Therefore the mean of the three distributions of I50VPR, V82APR and I84VPR differ by 15.16 , 16.36 and 15.24 respectively from that of WT complex. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 49;68;57 55;74;63 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. This suggests the binding free energy of SWCNTs for all four complexes are considerably higher than the binding affinities of the TMC114 to WT (-15.33), I50VPR (-10.88), V82APR (-12.20) and I84VPR (-11.66). 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 153;190;170 159;196;176 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Thus, despite the big differences in DeltaEvdw and DeltaGpb the total binding affinity of the I84VPR is lower than that of the V82APR by 8.4 kcal/mol (-48.22 vs -56.65 kcal/mol). 2012 Journal of molecular graphics & modelling Result HIV I84V;V82A 94;127 100;133 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Thus, the mean of the distribution for V82APR in chain B differ by 0.03 A from WT, 0.57 A from I50VPR and 0.79 A from I84VPR. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 95;118;39 101;124;45 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Thus, the mean values of I50VPR, V82APR and I84VPR are larger than those of the WT-SWCNT complex by 17.22 , 15.39 and 15.04 , which implies the more curling out of the flap tips in mutants than in the WT. 2012 Journal of molecular graphics & modelling Result HIV I50V;I84V;V82A 25;44;33 31;50;39 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. V82APR complex has a higher mean RMSD (1.41 A) than the WT (1.32 A), I50VPR mutant (1.22 A) and I84VPR mutant (1.37 A), with a respective standard deviation (SD) of 0.17, 0.12 0.19 and 0.20 A for WT, I50VPR, V82APR and I84VPR mutants. 2012 Journal of molecular graphics & modelling Result HIV I50V;I50V;I84V;I84V;V82A;V82A 69;200;96;219;0;208 75;206;102;225;6;214 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. V82APR distance runs parallel to WT up to 2.5ns and then it jumps to a higher value where it runs parallel to the I50VPR values up to 8.0 ns. 2012 Journal of molecular graphics & modelling Result HIV I50V;V82A 114;0 120;6 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Whereas for the V82APR (I84VPR) mutants, the mean and SD are 95.21 (96.33 ) and 4.91 (13.48 ). 2012 Journal of molecular graphics & modelling Result HIV I84V;V82A 24;16 30;22 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. Whereas, for the mutant V82APR (I84VPR), the mean and SD are 15.21 (14.42) A and 0.60 (0.51) A, respectively. 2012 Journal of molecular graphics & modelling Result HIV I84V;V82A 32;24 38;30 23144597 Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation. In addition, the invariant Thr 80, which is flanked by proline residues (Pro 79 - Thr 80 - Pro 81), has higher mobility in the mutant. 2012 Journal of chemical theory and computation Result HIV P79T 73 86 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Among the 7 screened mutations, 2 mutations D123E and V292I located at the polymerase domain and 5 (K366R, T369A, T369V, A371V and I375V) at the RT connection domain were further analyzed on the relationship between the mutations and drug resistance in SHDB. 2012 PloS one Result HIV A371V;D123E;I375V;K366R;T369A;T369V;V292I 121;44;131;100;107;114;54 126;49;136;105;112;119;59 Pol;RT 75;145 85;147 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. As the popular mutation pattern, mutations A371V and I375V were observed in 94% of ART patients. 2012 PloS one Result HIV A371V;I375V 43;53 48;58 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Five classes of mutations were observed at codon 369, with T369A (61%) and T369V (34%) as most common. 2012 PloS one Result HIV T369A;T369V 59;75 64;80 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The 9 mutations M41L, D67N, K70R, K103N, Y181C, M184V, T215Y, L283I and N348I resulted in resistance to NRTIs or NNRTIs, but the impact of 7 mutations at 6 positions (D123E, V292I, K366R, T369A, T369V, A371V and I375V) on antiviral drug response was unknown. 2012 PloS one Result HIV A371V;D123E;D67N;I375V;K103N;K366R;K70R;L283I;M184V;M41L;N348I;T215Y;T369A;T369V;V292I;Y181C 202;167;22;212;34;181;28;62;48;16;72;55;188;195;174;41 207;172;26;217;39;186;32;67;53;20;77;60;193;200;179;46 NNRTI;NRTI 113;104 119;109 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The D234E mutation does not confer a change in viral resistance to AZT as the IC50 for the mutant virus pNL4-3 D123E was not significantly different from that of pNL4-3-wild. 2012 PloS one Result HIV D234E 4 9 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The mutation D123E accounted for 39% of the 12 classes of mutations at position 123. 2012 PloS one Result HIV D123E 13 18 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The predominant mutations were V292I and K366R at codons 292 and 366 respectively, whose frequencies were 99% among all mutations at the corresponding position. 2012 PloS one Result HIV K366R;V292I 41;31 46;36 23152614 Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. Introducing a point mutation into the core domain (K41A) or a mutation at Cys30 to glycine (C30G) abrogated the ability of Tat to down regulate beta-catenin signaling in PDAs. 2012 The Journal of neuroscience Result HIV C30G;C30G;K41A 92;74;51 96;90;55 Tat 123 126 23152614 Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. The K41A Tat construct reduced TOPflash activity in U87MG by 16.6%. 2012 The Journal of neuroscience Result HIV K41A 4 8 Tat 9 12 23152614 Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. The Tat C30G construct enhanced beta-catenin activity by approximately 2-fold in PDAs. 2012 The Journal of neuroscience Result HIV C30G 8 12 Tat 4 7 23152614 Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. While Tat C30G also abrogated Tat inhibition of beta-catenin signaling in U87MG, it did not increase TOPflash activity above baseline. 2012 The Journal of neuroscience Result HIV C30G 10 14 Tat;Tat 6;30 9;33 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. Among the 77 (54.6%) patients harbouring viruses resistant to at least one molecule of the NNRTIs class, the most commonly detected DRM was the K103N/S (n=65, 46.1%). 2012 Journal of the International AIDS Society Result HIV K103N;K103S 144;144 151;151 NNRTI 91 97 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. Five additional viruses were predicted to be possibly resistant to ETV, including three viruses harbouring the E138A/G/Q/R DRM, one with the three DRMs K101E/H/I/P/R, Y181C, and G190A/S, and one with the three DRMs V90I, K101E/H/I/P/R, and G190A/S. 2012 Journal of the International AIDS Society Result HIV E138A;E138G;E138Q;E138R;G190A;G190A;G190S;G190S;K101E;K101E;K101H;K101H;K101I;K101I;K101P;K101P;K101R;K101R;V90I;Y181C 111;111;111;111;178;240;240;178;152;221;152;221;152;221;152;221;152;221;215;167 122;122;122;122;185;247;247;185;165;234;165;234;165;234;165;234;165;234;219;172 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. In two patients treated with NVP, viruses were found resistant to etravirine (ETV), the second generation NNRTI drug, due to the simultaneous presence of the Y181C and H221Y mutations. 2012 Journal of the International AIDS Society Result HIV H221Y;Y181C 168;158 173;163 NNRTI 106 111 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. Major NNRTIs DRMs were also obtained at positions P225H (n=12), K101E (n=11), Y181C (n=10), G190A (n=7), Y188L (n=6), V90I (n=5), E138A/G (n=5), M230L (n=4), A98G (n=3), H221Y (n=3), L100I (n=3), V179D (n=2), and V106I (n=1). 2012 Journal of the International AIDS Society Result HIV A98G;E138A;E138G;G190A;H221Y;K101E;L100I;M230L;P225H;V106I;V179D;V90I;Y181C;Y188L 158;130;130;92;170;64;183;145;50;213;196;118;78;105 162;137;137;97;175;69;188;150;55;218;201;122;83;110 NNRTI 6 12 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. No patient displayed viruses harbouring the K65R or K70E mutation selected by TDF. 2012 Journal of the International AIDS Society Result HIV K65R;K70E 44;52 48;56 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. Of the 56 NRTI-associated DRMs, M184V/I selected by 3TC/FTC was the most frequent (n=53, 37.6%), followed by any thymidine analogue resistance TAM mutation (n=15, 10.6%). 2012 Journal of the International AIDS Society Result HIV M184I;M184V 32;32 39;39 NRTI 10 14 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. Other TAM-1 were M41L (n=2) and L210W (n=1). 2012 Journal of the International AIDS Society Result HIV L210W;M41L 32;17 37;21 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. TAM-2 mutations included K219Q/E/R (n=4), D67N/G (n=4), and K70R (n=3). 2012 Journal of the International AIDS Society Result HIV D67G;D67N;K219E;K219Q;K219R;K70R 42;42;25;25;25;60 48;48;34;34;34;64 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. Ten patients had viruses with the TAM-1 mutation T215Y/F associated with AZT/D4T resistance. 2012 Journal of the International AIDS Society Result HIV T215F;T215Y 49;49 56;56 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. Two patients had HIV-1 strains harbouring the multi-NRTI resistance Q151M mutation associated with M184V/I and Y188L. 2012 Journal of the International AIDS Society Result HIV M184I;M184V;Q151M;Y188L 99;99;68;111 106;106;73;116 NRTI 52 56 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. As with the other CA mutants, infectivity of the R143A mutant HIV increased in the presence of HSP90AB1. 2013 Virology Result HIV R143A 49 54 Capsid 18 20 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. At the end of a 12-day continuous culture assay, CA-mutant infection of Jurkat E6-1 cells transduced with native HSP90AB1 increased by 1.7-fold for CAE128A+R132A to 5.4-fold for CAN139A over CA-mutant infection of nonactivated Jurkat E6-1 cells (Table 1). 2013 Virology Result HIV R132A 156 161 Capsid;Capsid;Capsid;Capsid 49;148;178;191 51;150;180;193 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. First, equal amounts of Jurkat E6-1 lysate extracted from nonactivated HSP90AB1-transduced and mutant HSP90AB1E42A+D88A-transduced cells were probed for HSP90AB1 and the FLAG epitope, and equal protein loading was confirmed by comparable detection of actin. 2013 Virology Result HIV D88A 115 119 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. In parallel, we included the PR-mutant PRI54V+V82A HIV as a positive control to validate the rescue by overexpression of HSP90AB1. 2013 Virology Result HIV V82A 46 50 PR;PR 29;39 31;41 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. N139A appeared to most benefit from cellular expression of HSP90AB1 and exhibited exponential growth with the potential to establish a spreading infection. 2013 Virology Result HIV N139A 0 5 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Overexpression of the nonfunctional HSP90AB1E42A+D88A mutant protein failed to increase CA-mutant infectivity beyond the level observed in nonactivated Jurkat E6-1 cells. 2013 Virology Result HIV D88A 49 53 Capsid 88 90 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. The N139A mutation in CA displays a normal WT-like stable core and normal core numbers per virion with no discernable defects in assembly, maturation, or viral RNA packaging, yet this mutation impairs HIV infectivity. 2013 Virology Result HIV N139A 4 9 Capsid 22 24 HIV infections 201 216 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. The P38A and Q63A+Q67A CA-mutant viruses are reported to have unstable cores, while the E45A and E128A+R132A mutations resulted in greater numbers of hyperstable cores per virion. 2013 Virology Result HIV E128A;E45A;P38A;Q63A;Q67A;R132A 97;88;4;13;18;103 102;92;8;17;22;108 Capsid 23 25 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. The R143A mutation in CA reduces the number of cores per virion but paradoxically results in a hyperstable core. 2013 Virology Result HIV R143A 4 9 Capsid 22 24 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. We ruled out the possible influence of retroviral-mediated cellular upregulation in Jurkat E6-1 cells simultaneously transduced with the same retroviral vector expressing the catalytically defective HSP90AB1E42A+D88A mutant. 2013 Virology Result HIV D88A 212 216 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? All of them (100%) showed also M184V RAM to lamivudine. 2012 PloS one Result HIV M184V 31 36 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Among patients carrying RAMs, 12/15 (80.0%) harboured RAMs associated to thymidine analogues (TAMs) (M41L, D67N, K70R, V75I, L210W, T215F/Y) (Table 3). 2012 PloS one Result HIV D67N;K70R;L210W;M41L;T215F;T215Y;V75I 107;113;125;101;132;132;119 111;117;130;105;139;139;123 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Four patients (22.2%) carried virus with only M184V and NNRTI mutations (Table 3). 2012 PloS one Result HIV M184V 46 51 NNRTI 56 61 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? One patient carried Q151M mutation, associated with M41L, D67N, T215F and M184V, conferring pan-nucleoside resistance, except to tenofovir. 2012 PloS one Result HIV D67N;M184V;M41L;Q151M;T215F 58;74;52;20;64 62;79;56;25;69 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? The M184V mutation was present in virus from 15 patients (83.3%), although never as the only mutation. 2012 PloS one Result HIV M184V 4 9 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? The most common mutation pattern was M184V and NNRTI mutations with one or more TAMs, which occurred in 12 (66.7%) patients. 2012 PloS one Result HIV M184V 37 42 NNRTI 47 52 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? The most frequent NNRTI mutations were K103N/S (27.8%), followed by Y181C (22.2%), V108I and G190A (16.7%), Y181V (11.1%), K101E and Y188L (5.6%) (Figure 2). 2012 PloS one Result HIV G190A;K101E;K103N;K103S;V108I;Y181C;Y181V;Y188L 93;123;39;39;83;68;108;133 98;128;46;46;88;73;113;138 NNRTI 18 23 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? The most frequent TAMs were T215F/Y (11/12, 91.7%), M41L (10/12, 83.3%), L210W (3/12, 27,3%), D67N (3/12, 25.0%), K70R (1/12, 8.3%) and V75I (1/12, 8.3%) (Table 3). 2012 PloS one Result HIV D67N;K70R;L210W;M41L;T215F;T215Y;V75I 94;114;73;52;28;28;136 98;118;78;56;35;35;140 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? There were no patients carrying either K65R or T69 insertion. 2012 PloS one Result HIV K65R 39 43 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. 1A), including changes D51G and L160V in the region N-terminal to the membrane leader sequence; H247Q in C2; E407K and K412E in V3; R428G and M437T in C3; E656K between the polar domain and the leucine zipper of TM; and V817I in the cytoplasmic tail. 2012 Retrovirology Result HIV D51G;E407K;E656K;H247Q;K412E;L160V;M437T;R428G;V817I 23;109;155;96;119;32;142;132;220 27;114;160;101;124;37;147;137;225 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. As described above, combined mutants such as E407K/E656K/V817I had apparently enhanced entry capacities on CrFK-fX4 cells, compared with those single mutants. 2012 Retrovirology Result HIV E407K;E656K;V817I 45;51;57 50;56;62 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. In contrast, the R428G mutation was associated with severely arrested entry into GFox cells, but had only a weak influence on the entry efficiency in CrFK-fX4 cells. 2012 Retrovirology Result HIV R428G 17 22 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. Mutations in TM, including E656K and its double mutant E656K/V817I contribute strongly to both the loss of entry into GFox cells and enhanced entry into CrFK-fX4 cells. 2012 Retrovirology Result HIV E656K;E656K;V817I 27;55;61 32;60;66 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. Other single mutants such as D51G, L160V, K412E, M437T, and V817I had a more modest negative effect on CD134-mediated entry into GFox cells and also cause a minor reduction or enhancement on entry into CrFK-fX4 cells. 2012 Retrovirology Result HIV D51G;K412E;L160V;M437T;V817I 29;42;35;49;60 33;47;40;54;65 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. Similar results were noted with multiple mutations where E407K was present (Table 1). 2012 Retrovirology Result HIV E407K 57 62 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. The H247Q mutation was unique in that it had a slight enhancing effect on CD134-mediated entry and an approximate 2-fold enhancement on CXCR4-mediated entry. 2012 Retrovirology Result HIV H247Q 4 9 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. The results indicated that E407K was a critical amino acid substitution that totally abrogated CD134-mediated entry on GFox cells and at the same time stimulated CXCR4-only entry by over 12-fold. 2012 Retrovirology Result HIV E407K 27 32 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. Thus, mutations in TM working alone or in combination with critical residues in SU such as E407K affected the entry process, possibly through interactions associated with the fusion step. 2012 Retrovirology Result HIV E407K 91 96 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. Thus, the R428G mutation contributes to the negative influence on CD134 usage, but makes no apparent contribution to HSPG binding or CXCR4-mediated entry. 2012 Retrovirology Result HIV R428G 10 15 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Among virologically failing patients E157Q was noted in one patient with N155H mutant, in three E157Q variant was present at baseline and consistently in the sequences obtained on RAL therapy while in two patients either R263K or L74IL were present at baseline and disappeared in the subsequent sequences on virologically unsuccessful treatment. 2012 BMC infectious diseases Result HIV E157Q;E157Q;L74I;L74L;N155H;R263K 37;96;230;230;73;221 42;101;235;235;78;226 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Baseline polymorphisms, including the most prevalent E157Q analyzed separately, were not associated with the virologic failure on RAL [p=0.5, OR 1.56 (95% CI: 0.35-7.11) and p=0.38, OR 1.83 (95% CI:0.38-10.05), respectively]. 2012 BMC infectious diseases Result HIV E157Q 53 58 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Development of drug resistance mutations followed two patterns: major N155H with or without subsequent accessory V151I, E92EQ, V151I, G163R mutants (three cases) and Q148H accompanied by G140S mutant (one case) (Figure 3B). 2012 BMC infectious diseases Result HIV E92E;E92Q;G140S;G163R;N155H;Q148H;V151I;V151I 120;120;187;134;70;166;113;127 125;125;192;139;75;171;118;132 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. In 14 cases with virologic success accessory mutations were present prior to the raltegravir introduction (11 sequences with E157Q, one of each L68V/E157Q, T97A, V151I). 2012 BMC infectious diseases Result HIV E157Q;E157Q;L68V;T97A;V151I 125;149;144;156;162 130;154;148;160;167 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. It must be noted, that three of the patients with developed drug resistance were heavily experienced with reverse transcriptase (RT) and protease (PR) mutations (patient 1: RT: M41L, K103N, M184V, T215S; PR: L10I; patient 2: PR: M41L, V118I, K103N, M184V, L210W, T215S, RT: L10I, M46I, I54V, L63P, A71T, V82A, L90M, patient 4: RT: K103N, M184V, P225H, F227L), while one patient (number 3) due to endocarditis and kidney failure was treated with live-saving but suboptimal therapy which consisted solely of ritonavir-boosted saquinavir and raltegravir. 2012 BMC infectious diseases Result HIV A71T;F227L;I54V;K103N;K103N;K103N;L10I;L10I;L210W;L63P;L90M;M184V;M184V;M184V;M41L;M41L;M46I;P225H;T215S;T215S;V118I;V82A 298;352;286;183;242;331;208;274;256;292;310;190;249;338;177;229;280;345;197;263;235;304 302;357;290;188;247;336;212;278;261;296;314;195;254;343;181;233;284;350;202;268;240;308 RT;PR;PR;PR;PR;RT;RT;RT;RT 106;137;147;204;225;129;173;270;327 127;145;149;206;227;131;175;272;329 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Other mutations and polymorphisms observed only in subtype B integrase sequences were L68V, T97A and V151I, while in non-B sequences R263K, E138D, L68IL and L74IL variants were noted (Figure 1b, Table 1). 2012 BMC infectious diseases Result HIV E138D;L68I;L68L;L68V;L74I;L74L;R263K;T97A;V151I 140;147;147;86;157;157;133;92;101 145;152;152;90;162;162;138;96;106 IN 61 70 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. The predominating E157Q polymorphism was found in 47.9% of the subtype B sequences and associated with injection drug use (69.6% of the sequences with E157Q were derived from the IDU patients). 2012 BMC infectious diseases Result HIV E157Q;E157Q 18;151 23;156 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. Although I85V is a nonpolymorphic PI-selected mutation, it does not result in resistance to PI. 2012 BMC infectious diseases Result HIV I85V 9 13 PI;PI 34;92 36;94 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. Among NNRTI-related DR mutations, K103N and Y181C were found in 3 samples (1.0%). 2012 BMC infectious diseases Result HIV K103N;Y181C 34;44 39;49 NNRTI 6 11 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. Importantly, Y181C forms the foundation for high-level ETR and RPV resistance as an addition of some single mutations and many double mutations causes high-level resistance to these drugs. 2012 BMC infectious diseases Result HIV Y181C 13 18 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. K103N causes high-level resistance to nevirapine (NVP) and efavirenz (EFV). 2012 BMC infectious diseases Result HIV K103N 0 5 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. Only 1 NRTI-related DR mutation, M184I (0.33%, n=1), was detected. 2012 BMC infectious diseases Result HIV M184I 33 38 NRTI 7 11 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. The PI-related DR included: I85V (0.67%, n=2), M46I (0.33%, n=1) and L90M (0.33%, n= 1). 2012 BMC infectious diseases Result HIV I85V;L90M;M46I 28;69;47 32;73;51 PI 4 6 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. The reason for their presence might be due to cross-resistance, for example 3TC induced M184I/V but also rendered resistance to FTC. 2012 BMC infectious diseases Result HIV M184I;M184V 88;88 95;95 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. Three individuals were found to have one other NNRTI-related mutation (K103NS, K101E and G190A) each (0.33%). 2012 BMC infectious diseases Result HIV G190A;K101E;K103N;K103S 89;79;71;71 94;84;77;77 NNRTI 47 52 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. Y181C causes high-level resistance to NVP and intermediate resistance to EFV, etravirine (ETR) and rilpivirine (RPV). 2012 BMC infectious diseases Result HIV Y181C 0 5 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. 5 shows that N348I mutant RT has decreased RNase H activity for all substrates used in this assay. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 13 18 RT 26 28 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. 6B) templates suggesting that resistance mutant N348I does not have any significant effect on the unblocking of EFdA-MP containing primers (RNA vs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 48 53 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. ATP-dependent unblocking of EFdA-MP terminated primers by WT and N348I RTs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 65 70 RT 71 74 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Effect of EFdA-MP on RNase H activity of WT and N348I RTs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 48 53 RT 54 57 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Effect of EFdA-MP on Translocation of WT and N348I mutant of HIV-1 RT. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 45 50 RT 67 69 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. However, the N348I mutation in the background of AZT resistance mutations D67N, K70R, L210Q and T215F showed a 2-fold increase in unblocking EFdA-MP containing primers both with DNA and RNA templates. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV D67N;K70R;L210Q;N348I;T215F 74;80;86;13;96 78;84;91;18;101 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. In addition, another mutant HIV-1 RT (A62V/V75I/F77L/F116Y/Q151M) was included in drug susceptibility assays. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV A62V;F116Y;F77L;Q151M;V75I 38;53;48;59;43 42;58;52;64;47 RT 34 36 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Inhibition of WT and N348I mutant of HIV-1 RT. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 21 26 RT 43 45 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. N348I, D67N/K70R/L210Q/T215F and D67N/K70R/L210Q/T215F/N348I RTs were inhibited by EFdA-TP and ENdA-TP with similar efficiency compared to the WT enzyme. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV D67N;D67N;K70R;K70R;L210Q;L210Q;N348I;T215F;T215F;N348I 7;33;12;38;17;43;55;23;49;0 11;37;16;42;22;48;60;28;54;5 RT 61 64 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Since EFdA-MP-terminated primers bind predominantly in a pre-translocation mode we expected that EFdA-MP will be efficiently unblocked by both WT and N348I RTs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 150 155 RT 156 159 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The bands marked as 'Rescued Primer" have comparable product for the WT and N348I mutant enzyme for both DNA. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 76 81 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The connection subdomain mutation N348I has been related to the altered DNA binding affinity and processivity of the mutant enzyme compared to the WT RT. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 34 39 RT 150 152 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The inhibition of WT, N348I, D67N/K70R/L210Q/T215F, D67N/K70R/L210Q/T215F/N348I mutants of HIV-1 RT by EFdA-TP and ENdA-TP was assessed by a primer extension assay. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV D67N;D67N;K70R;K70R;L210Q;L210Q;N348I;T215F;T215F;N348I 29;52;34;57;39;62;74;45;68;22 33;56;38;61;44;67;79;50;73;27 RT 97 99 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The inhibitors used here to characterize the susceptibility of N348I to various drugs are adenosine analogs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 63 68 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The template/primers containing EFdA-MP, ddAMP, or without inhibitor incorporated at the 3' end of the primer were used in RNase H assays with WT and N348I RTs in a time dependent manner. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 150 155 RT 156 159 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Therefore, similar to WT RT, the mutant N348I RT is also inhibited by EFdA-TP via the same mechanism. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Result HIV N348I 40 45 RT;RT 25;46 27;48 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. Also, the mutations N88D and L90M (NFV resistance) were more frequently detected by DNA-OLA in patients with virologic failure (p < 0.001 and p < 0.05, respectively; WRS test). 2013 BMC infectious diseases Result HIV L90M;N88D 29;20 33;24 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. Detection of the M184V, N88D and L90M substitutions by RNA OLA was highly sensitive for virologic failure (sensitivity: 0.93, 1.0 and 1.0; binary classification test). 2013 BMC infectious diseases Result HIV L90M;M184V;N88D 33;17;24 37;22;28 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The ability to obtain positive results with the RNA OLA, along with the detection of mutations M184V, N88D and L90M, may thus suggest virologic failure in this cohort of patients. 2013 BMC infectious diseases Result HIV L90M;M184V;N88D 111;95;102 115;100;106 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The detection of the M184V reverse transcriptase mutation (indicating 3TC resistance) by any of the three methods (genotyping, RNA-OLA or DNA-OLA) was significantly more frequent in patients with virologic failure (p = 0.07b, p < 0.05c and p < 0.001c). 2013 BMC infectious diseases Result HIV M184V 21 26 RT 27 48 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The detection of the same mutations (M184V, N88D and L90M) by DNA-OLA yielded a slightly lower sensitivity of 0.86, 0.9 and 0.75 for virologic failure, but the assay could be performed in almost all patient samples (regardless of virologic success or failure) indicating that virologic failure may indeed be attributed to resistance development at these three residues (these specific mutations appear significantly more frequently in failing patients, see Table 2). 2013 BMC infectious diseases Result HIV L90M;M184V;N88D 53;37;44 57;42;48 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The M184V reverse transcriptase mutation was detected in 80% of the sequenced RNA samples and tested positive in 74% and 47% by RNA-OLA and DNA-OLA, whereas thymidine associated mutations (TAMs: M41L, D67N, K70R, L210W, T215F/Y, K219Q/E) were detected in 50% of sequenced viral RNA. 2013 BMC infectious diseases Result HIV D67N;K219E;K219Q;K70R;L210W;M184V;M41L;T215F;T215Y 201;229;229;207;213;4;195;220;220 205;236;236;211;218;9;199;227;227 RT 10 31 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The N88D and L90M protease mutations were detected in 36% and 21% of genotyping samples, in 25% and 20% of RNA-OLA samples, and in 42% and 44% of DNA-OLAs, respectively. 2013 BMC infectious diseases Result HIV L90M;N88D 13;4 17;8 PR 18 26 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The protease mutation D30N was detected in 43% of RNA genotyping samples and in 0% and 2% of available RNA- and DNA-OLA samples. 2013 BMC infectious diseases Result HIV D30N 22 26 PR 4 12 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The protease mutation D30N was not detected more commonly in cases of virologic failure (by any of the assays used), neither were TAMs selected differentially in failing vs. 2013 BMC infectious diseases Result HIV D30N 22 26 PR 4 12 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. Using RNA-OLA and DNA-OLA, the T215Y and T215F mutations tested positive in 47% and 42%, respectively. 2013 BMC infectious diseases Result HIV T215F;T215Y 41;31 46;36 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. In contrast to mutant PRI50V, mutation of R8Q has altered the type of interaction rather than eliminated interactions. 2013 Journal of medicinal chemistry Result HIV R8Q 42 45 PR 22 24 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Influence of D30N on PR structure and its interaction with inhibitor 1. 2013 Journal of medicinal chemistry Result HIV D30N 13 17 PR 21 23 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutation V82A introduces the smaller Ala side chain, leading to the loss of C-H...pi interactions with the P1 phenyl group of inhibitor 1 compared with those in the wild type complex. 2013 Journal of medicinal chemistry Result HIV V82A 9 13 PI 82 84 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutations I50V and R8Q alter the dimer interface and interactions with inhibitor 1. 2013 Journal of medicinal chemistry Result HIV I50V;R8Q 10;19 14;22 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutations I54M and V82A produce compensating shifts in the 80s loop residues. 2013 Journal of medicinal chemistry Result HIV I54M;V82A 10;19 14;23 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Similar changes in interactions of residues 30 and 88 have been reported in mutants containing D30N and N88D and also proposed to effect inhibition. 2013 Journal of medicinal chemistry Result HIV D30N;N88D 95;104 99;108 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. The mutation of Ile50 to Val50 also affects the inter-subunit interactions. 2013 Journal of medicinal chemistry Result HIV I50V 16 30 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. All 20 sequences with K65R had intermediate or high-level predicted resistance to tenofovir and the three sequences with K70E had low-level predicted tenofovir resistance. 2012 Journal of the International AIDS Society Result HIV K65R;K70E 22;121 26;125 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. In addition to K65R, other transmitted tenofovir-associated resistance mutations included K70E, seen in three subtype B sequences (0.015%, 95% CI: 0.004 to 0.04) and three or more TAMs (inclusive of either M41L or L210W) seen in 54/19,823 sequences (0.27%, 95% CI: 0.2 to 0.4), the majority of which (46/54) were subtype B sequences. 2012 Journal of the International AIDS Society Result HIV K65R;K70E;L210W;M41L 15;90;214;206 19;94;219;210 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. There was a trend in K65R occurring more frequently in subtype B (14/9783, 0.14%) compared to aggregated non-subtype B sequences (6/10,034, 0.06%; p=0.07). 2012 Journal of the International AIDS Society Result HIV K65R 21 25 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. There was no significant difference between the number of K65R sequences that were collected in the five-year period between 1999 and 2003 (when tenofovir became more widely used) and those collected in the five-year period between 2004 and 2008 (9/20 vs. 2012 Journal of the International AIDS Society Result HIV K65R 58 62 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. There was no significant difference in K65R occurrence in subtype C (3/3198, 0.09%) compared to aggregated non-subtype C sequences (17/16,608, 0.10%; p=1) or to subtype B sequences (p=0.80). 2012 Journal of the International AIDS Society Result HIV K65R 39 43 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. There were 20/19,823 sequences with K65R (0.1%, 95% CI: 0.06 to 0.15; Table 2), 14/9783 (0.14%) in subtype B from North/Central America and Europe, 3/3198 (0.09%) in subtype C from Africa, 2/1797 (0.11%) in CRF01_AE from Vietnam and 1/594 (0.17%) in subtype G from Europe. 2012 Journal of the International AIDS Society Result HIV K65R 36 40 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Transmitted K65R was observed among sequences that were collected from 1999 until 2008. 2012 Journal of the International AIDS Society Result HIV K65R 12 16 23308067 Human tetherin exerts strong selection pressure on the HIV-1 group N Vpu protein. Mutation of the serine phosphorylation sites (S52A/S56A) as well as a G53D substitution found in several N-Vpus disrupted this interaction of NL4-3 and YBF30 Vpus. 2012 PLoS pathogens Result HIV G53D;S52A;S56A 70;46;51 74;50;55 Vpu;Vpu 107;158 111;162 23308067 Human tetherin exerts strong selection pressure on the HIV-1 group N Vpu protein. The results revealed that four TMD amino acid substitutions (E15A, V19A, I25L and V26L) were sufficient to render the SIVcpz Vpu active against human tetherin, while the reciprocal changes disrupted the effect of the YBF30 Vpu on virus release (Figure 4B). 2012 PLoS pathogens Result HIV E15A;I25L;V19A;V26L 61;73;67;82 65;77;71;86 Vpu;Vpu 125;223 128;226 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Again, the topology of the dendrogram showed the strong association between L76V and M46I (bootstrap value = 0.95) (Figure 3B). 2013 PloS one Result HIV L76V;M46I 76;85 80;89 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Among subtype B samples, the major PI RAM significantly correlating as pairs with L76V were: M46I, I54L/M, Q58E, V82F, I84V, and L90M. 2013 PloS one Result HIV I54L;I54M;I84V;L76V;L90M;M46I;Q58E;V82F 99;99;119;82;129;93;107;113 105;105;123;86;133;97;111;117 PI 35 37 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Among the 179 patients of the study, 41 (23%) displayed plasma virus with L76V, although they never received lopinavir. 2013 PloS one Result HIV L76V 74 78 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Among the 29,643 sequences, 446 displayed the L76V mutation in protease, leading to an overall prevalence of 1.50%. 2013 PloS one Result HIV L76V 46 50 PR 63 71 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Among the 8 patients exhibiting plasma virus with the single L76V mutation, 5 were receiving a lopinavir-based therapy as first line regimen, and half were infected with CRF02_AG (n = 4). 2013 PloS one Result HIV L76V 61 65 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Analysis of Covariation of L76V among Protease Mutations. 2013 PloS one Result HIV L76V 27 31 PR 38 46 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. At the time of first detection of the L76V mutation, there was no significant difference in the nature of PI received between patients infected with B and "non-B" subtypes (Table 1). 2013 PloS one Result HIV L76V 38 42 PI 106 108 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. At time of the first detection of the L76V mutation, median time since HIV infection diagnosis and median time under antiretroviral-based regimen were both shorter in "non-B" patients compared with subtype B patients (8 vs 11 years, P<0.0001; and 7 vs 8 years, P = 0.004, respectively) (Table 1). 2013 PloS one Result HIV L76V 38 42 HIV infections 71 84 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Demographic, Therapeutic, and Virological Characteristics of Patients Displaying L76V-mutated Viruses. 2013 PloS one Result HIV L76V 81 85 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Furthermore, we performed average linkage hierarchical agglomerative cluster analysis to investigate if the protease mutations pairwise associated with L76V raised in specific evolutionary pathways. 2013 PloS one Result HIV L76V 152 156 PR 108 116 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In our database, a similar prevalence of the L76V mutation was observed among B- and "non-B"-infected patients until 2008 (Figure 1). 2013 PloS one Result HIV L76V 45 49 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In subtype B samples, the strongly correlated pairs of mutations L76V and M46I clustered along with the I84V and K55R mutations. 2013 PloS one Result HIV I84V;K55R;L76V;M46I 104;113;65;74 108;117;69;78 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Likewise, this cluster was confirmed also in HIV-1 "non-B" sequences, where the major PI RAM L76V, M46I, I54L and I84V grouped together with the secondary one A71V (bootstrap value = 0.86). 2013 PloS one Result HIV A71V;I54L;I84V;L76V;M46I 159;105;114;93;99 163;109;118;97;103 PI 86 88 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Only 8 samples (8/179, 4.5%) were found with L76V as the sole PI RAM, with a higher frequency in "non-B" than in subtype B samples (10% vs 2%, P = 0.014). 2013 PloS one Result HIV L76V 45 49 PI 62 64 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Prevalence of L76V Mutation Over Time. 2013 PloS one Result HIV L76V 14 18 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Protease Mutation Patterns of L76V-mutated Viruses among HIV-1 B and "non-B" Subtypes. 2013 PloS one Result HIV L76V 30 34 PR 0 8 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Regarding secondary PI RAM the strongest associations were found with the mutations K55R (covariation frequency 36.4%, phi = 0.32), I54V (covariation frequency 23.3%, phi = 0.27), and L33F (covariation frequency 27.2%, phi = 0.27). 2013 PloS one Result HIV I54V;K55R;L33F 132;84;184 136;88;188 PI 20 22 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Regarding the 446 samples with L76V mutation in PI-experienced patients, known clinical and therapeutic history for further analyzes were available in 179 patients. 2013 PloS one Result HIV L76V 31 35 PI 48 50 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Significant differences in the prevalence of PI RAMs detected with the L76V between subtype B and "non-B" samples were found at 4 positions with a higher prevalence of the V32I, M46I/L, V82A/F/L/T/S and L90M mutations in subtype B than in "non-B" samples: 10 vs 0%, P = 0.04; 92 vs 82%, P = 0.036; 52 vs 26%, P = 0.0011; and 42 vs 18%, P = 0.002, respectively. 2013 PloS one Result HIV L76V;L90M;M46I;M46L;V32I;V82A;V82F;V82L;V82S;V82T 71;203;178;178;172;186;186;186;186;186 75;207;184;184;176;198;198;198;198;198 PI 45 47 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Similar pairwise correlations were observed in "non-B" sequences (phi >0.10, P<0.0001), with an additional correlation with the I47V major PI RAM (covariation frequency 72.8%, phi = 0.27). 2013 PloS one Result HIV I47V 128 132 PI 139 141 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Since 2008 the prevalence of L76V was higher in "non-B"-infected than in B-infected patients each year (P = 0.02 in 2008, P = 0.006 in 2009; and P = 0.001 in 2010). 2013 PloS one Result HIV L76V 29 33 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The L90M mutation was co-present with the L76V in 49 (11.6%) patients (phi = 0.12). 2013 PloS one Result HIV L76V;L90M 42;4 46;8 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The most prevalent PI RAM detected with L76V was the M46I/L, both in subtype B and "non-B" samples, found in 92 and 82% of cases, respectively. 2013 PloS one Result HIV L76V;M46I;M46L 40;53;53 44;59;59 PI 19 21 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The number of major PI RAMs associated with L76V mutation was lower in "non-B" samples than in subtype B samples (3 vs 4, P = 0.0001). 2013 PloS one Result HIV L76V 44 48 PI 20 22 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The prevalence of major PI RAMs found with the L76V is depicted in Figure 2. 2013 PloS one Result HIV L76V 47 51 PI 24 26 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The strongest associations were observed with the M46I (covariation frequency 25.9%, phi = 0.39), and I84V major PI RAM (covariation frequency 28.4%, phi = 0.28). 2013 PloS one Result HIV I84V;M46I 102;50 106;54 PI 113 115 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Then, the most prevalent mutation found with L76V was the V82A/F/L/T/S (52%) in subtype B samples and I84V (36%) in "non-B" samples. 2013 PloS one Result HIV I84V;L76V;V82A;V82F;V82L;V82S;V82T 102;45;58;58;58;58;58 106;49;70;70;70;70;70 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. This cluster was linked to L24I, I54V, and V82A mutations. 2013 PloS one Result HIV I54V;L24I;V82A 33;27;43 37;31;47 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. We also assessed the PI pre-exposure showing that patients infected with "non-B" subtypes received a lower number of PI before the selection of the L76V mutation than those infected with B subtype (2 vs 3, P = 0.016), although the duration of PI-based regimen was similar in the 2 groups of patients. 2013 PloS one Result HIV L76V 148 152 PI;PI;PI 21;117;243 23;119;245 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. When regarding the prevalence of the L76V mutation among the PI-resistant viruses, containing at least one major PI RAM, it was found at 5.42% (430/7,934). 2013 PloS one Result HIV L76V 37 41 PI;PI 61;113 63;115 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. 3, however, any combination including G330E was no more restrictive, and even slightly less restrictive, than the relevant controls lacking it. 2013 Virus research Result HIV G330E 38 43 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. According to this prediction tool, introduction of the R332G and R335G mutations caused significant changes in all 3 main variable regions (v1, v2, v3). 2013 Virus research Result HIV R332G;R335G 55;65 60;70 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Although the overall level of restriction was smaller than in TE671 cells, as observed before, it is worth noting that expression of either R332G-R335G or G330E-R332G-R335G in Sup-T1 cells inhibited HIV-1 almost as efficiently as TRIM5alphaRh. 2013 Virus research Result HIV G330E;R332G;R332G;R335G;R335G 155;140;161;146;167 160;145;166;151;172 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Combining G330E with mutations at Arg332 or Arg335. 2013 Virus research Result HIV G330E 10 15 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. G330E-R332G-R335G was less efficient than R332G-R335G at binding in vitro assembled HIV-1 CA-NC complexes, supporting the finding that the G330E mutation does not increase restriction when it is combined with Arg332 and Arg335 mutations. 2013 Virus research Result HIV G330E;R332G;R332G;R335G;R335G;G330E 139;6;42;12;48;0 144;11;47;17;53;5 NC;Capsid 93;90 95;92 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. However, G330D was not as restrictive as G330E, and only the latter mutant was retained for further investigation. 2013 Virus research Result HIV G330D;G330E 9;41 14;46 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. However, it was approximately 2-times less restrictive than the double mutation R332G-R335G and 10-times less restrictive than the Rhesus macaque ortholog. 2013 Virus research Result HIV R332G;R335G 80;86 85;91 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. In order to test whether G330E TRIM5alphaHu would efficiently disrupt the spread of HIV-1 in susceptible cells, we infected Sup-T1 cells expressing WT, G330E or R332G-R335G TRIM5alphaHu with HIV-1NL4-3. 2013 Virus research Result HIV G330E;G330E;R332G;R335G 25;152;161;167 30;157;166;172 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. In this preliminary analysis, G330E was found to be as efficient at inhibiting HIV-1 as previously described mutation R332G. 2013 Virus research Result HIV G330E;R332G 30;118 35;123 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Interestingly, the triple mutant (G330ER332G-R335G) had a surface structure that was very different from that of the R332G-R335G mutant and, in fact, more closely resembled that of the WT protein. 2013 Virus research Result HIV R332G;R335G;R335G;R332G 117;45;123;39 122;50;128;44 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Like before, G330E inhibited HIV-1 as efficiently as mutations in Arg332 or Arg335, but G330E-R332G-R335G was not more efficient than R332G-R335G. 2013 Virus research Result HIV G330E;G330E;R332G;R332G;R335G;R335G 13;88;94;134;100;140 18;93;99;139;105;145 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Only the mutation G330E of G4 conferred a strong level of HIV-1 resistance, close to 10-fold. 2013 Virus research Result HIV G330E 18 23 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Previously, we found that R332G and R335G had additive effects on HIV-1 replication. 2013 Virus research Result HIV R332G;R335G 26;36 31;41 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Single mutants G330E and R335G were not observed to significantly bind in vitro assembled HIV-1 CA-NC complexes in these experimental conditions, but this may be simply due to a lack of sensitivity of our assay. 2013 Virus research Result HIV G330E;R335G 15;25 20;30 NC;Capsid 99;96 101;98 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Specifically, G330E restricts HIV-1 in these cells about as efficiently as R332G and R335G do (about 10-fold compared with the empty vector control), and G330E does not potentiate HIV-1 restriction by the R332G-R335G double mutant. 2013 Virus research Result HIV G330E;G330E;R332G;R332G;R335G;R335G 14;154;75;205;85;211 19;159;80;210;90;216 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Spreading of HIV-1 in cells expressing G330E or R332G-R335G TRIM5alphaHu was apparent but no clear peak was visible during the course of the experiment. 2013 Virus research Result HIV G330E;R332G;R335G 39;48;54 44;53;59 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. That HIV-1 was roughly equally inhibited in G330E and R332G-R335G cells, despite the fact that the latter is more efficient at inhibiting HIV-1 single-cycle vector transduction, indicates that restriction of vector transduction may not always be a faithful model for the restriction of HIV-1 propagation. 2013 Virus research Result HIV G330E;R332G;R335G 44;54;60 49;59;65 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. The fact that G330E was more restrictive than the parental clone G4 was probably due to the presence of mitigating mutations in clone G4, such as Y329C. 2013 Virus research Result HIV G330E;Y329C 14;146 19;151 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. The negatively charged glutamic acid brought by the G330E mutation likewise affects the protein charge. 2013 Virus research Result HIV G330E 52 57 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Therefore, G330E has a mitigating effect on HIV-1 restriction stemming from removing positive charges in the v1 region. 2013 Virus research Result HIV G330E 11 16 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Therefore, transduction of G330E or R332G-R335G TRIM5alphaHu is able to efficiently attenuate the spread of HIV-1 in susceptible cells, without completely disrupting it. 2013 Virus research Result HIV G330E;R332G;R335G 27;36;42 32;41;47 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. These observations help explain why G330E-R332G-R335G was slightly less restrictive than the 332-335 double mutant. 2013 Virus research Result HIV G330E;R332G;R335G 36;42;48 41;47;53 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. This mutation alone abolishes the slight level of restriction (2-fold) conferred by over-expression of the wild-type (WT) TRIM5alphaHu, and thus it is likely that it would also decrease restriction when combined with G330E, although we did not test this. 2013 Virus research Result HIV G330E 217 222 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Thus, HIV-1 restriction in TE671-B3 cells was due to a combination effect involving 2 or 3 of the substitutions found in this clone, while restriction in TE671-G4 cells was explained by mutation G330E. 2013 Virus research Result HIV G330E 195 200 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Thus, we aimed at analyzing whether the inhibition of HIV-1 conferred by G330E was, similarly, additive to that of R332G, R335G, or the double mutant R332G-R335G. 2013 Virus research Result HIV G330E;R332G;R332G;R335G;R335G 73;115;150;122;156 78;120;155;127;161 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. To analyze whether G330E and other mutants would inhibit HIV-1 when stably expressed in lymphocytes, Sup-T1 cells were transduced with the MIP-TRIM5alpha vectors. 2013 Virus research Result HIV G330E 19 24 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. TRIM5alphaRh and both R332G-R335G and G330E-R332G-R335G mutants of TRIM5alphaHu clearly bound in vitro assembled CA-NC complexes, and the strength of the interaction roughly correlated with the magnitude of restriction. 2013 Virus research Result HIV G330E;R332G;R332G;R335G;R335G 38;22;44;28;50 43;27;49;33;55 NC;Capsid 116;113 118;115 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Two of those were the R332G mutation that has been well-characterized by others. 2013 Virus research Result HIV R332G 22 27 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. We found that introduction of an aspartic acid significantly (3- to 4-fold) inhibited HIV-1 replication, while G330A or G330S had little or no effect. 2013 Virus research Result HIV G330A;G330S 111;120 116;125 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. 1A) and examined their anti-HIV activity against T-20S138A-resistant HIV-1 (Table 2). 2013 The international journal of biochemistry & cell biology Result HIV S138A 53 58 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. 1B), at passage 28 (P-28), when T-20S138A concentration was 51.2 nM (P-28, 51.2 nM), isoleucine at position 37 in the gp41 was substituted to asparagine (I37N). 2013 The international journal of biochemistry & cell biology Result HIV I37N 154 158 gp41 118 122 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. 1C), at P-28 (512 nM) and at P-40 (2 muM), E137K in the gp41, and L33S and I69L in the gp41 emerged, respectively. 2013 The international journal of biochemistry & cell biology Result HIV E137K;I69L;L33S 43;75;66 48;79;70 gp41;gp41 56;87 60;91 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. All peptides sufficiently suppressed HIV-1I69L, suggesting that I69L may be a secondary mutation or a polymorphism. 2013 The international journal of biochemistry & cell biology Result HIV I69L;I69L 42;64 46;68 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. An HIV-1NL4-3 strain containing a D36G substitution, which improves replication kinetics, was used as a wild-type virus (HIV-1WT) and for the construction of various mutants, as described. 2013 The international journal of biochemistry & cell biology Result HIV D36G 34 38 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Antiviral activity of E137K-modified peptides. 2013 The international journal of biochemistry & cell biology Result HIV E137K 22 27 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. At P-60 (3.3 muM), L44M and N126K in the gp41 further emerged. 2013 The international journal of biochemistry & cell biology Result HIV L44M;N126K 19;28 23;33 gp41 41 45 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. At P-60, the resistance of selected viruses from HIV-1WT and HIV-1N43D/S138A to T-20S138A, reached approximately 110- and 200-fold, respectively. 2013 The international journal of biochemistry & cell biology Result HIV S138A;S138A 84;71 89;76 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. C34E137K and C34E137K/S138A significantly suppressed all HIV-1 variants tested except for HIV-1I37N/L44M/N126K by C34E137K. 2013 The international journal of biochemistry & cell biology Result HIV L44M;N126K;E137K;S138A 100;105;16;22 104;110;21;27 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Collectively, these data suggest that L44M has as a role in HIV-1 resistance as a secondary mutation. 2013 The international journal of biochemistry & cell biology Result HIV L44M 38 42 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Complexes of N36 and C34 containing the S138A and E137K/S138A substitutions (N36/C34S138A and N36/C34E137K/S138A, respectively), showed higher thermal stability than N36/C34. 2013 The international journal of biochemistry & cell biology Result HIV E137K;S138A;S138A;E137K;S138A;S138A 101;107;84;50;40;56 106;112;89;55;45;61 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Consistent with a previous report, the L33S mutation did not significantly affect the replication kinetics and infectivity compared with those of HIV-1WT. 2013 The international journal of biochemistry & cell biology Result HIV L33S 39 43 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. During the passage of HIV-1N43D/S138A, a synonymous mutation at amino acid position L44, TTG to CTG, was observed. 2013 The international journal of biochemistry & cell biology Result HIV N43D;S138A 27;32 31;37 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. E137K was also associated with N43D mutation in vivo, and restored infectivity impaired by N43D. 2013 The international journal of biochemistry & cell biology Result HIV N43D;N43D;E137K 31;91;0 35;95;5 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Finally, we also used as a control C34N126K, a modified version of C34 that includes the resistance-associated N126K substitution that effectively suppress replication of C34-resistant HIV-1 in vitro. 2013 The international journal of biochemistry & cell biology Result HIV N126K 111 116 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. HIV-1L33S/N43D/S138A and HIV-1I37N/L44M/N126K showed high resistance to T-20E137K, indicating that the resistance mechanism of T-20E137K is similar to that of T-20S138A. 2013 The international journal of biochemistry & cell biology Result HIV L44M;N126K;N43D;S138A;S138A 35;40;10;15;163 39;45;14;20;168 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. HIV-1WT or T-20-resistant HIV-1N43D/S138A were used for selection of T-20S138A-resistant HIV-1. 2013 The international journal of biochemistry & cell biology Result HIV S138A 36 41 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. However, introduction of L44M to HIV-1I37N/N126K (HIV-1I37N/L44M/N126K) remarkably enhanced resistance to T-20 derivatives. 2013 The international journal of biochemistry & cell biology Result HIV L44M;N126K;L44M;N126K 60;65;25;43 64;70;29;48 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Introduction of E137K into N43D/S138A enhanced the replication kinetics, and further addition of L33S to N43D/E137K/S138A resulted in equivalent replication kinetics compared with HIV-1N43D/E137K/S138A. 2013 The international journal of biochemistry & cell biology Result HIV N43D;E137K;E137K;N43D;S138A;S138A;E137K;L33S;N43D;S138A 185;110;190;105;116;196;16;97;27;32 189;115;195;109;121;201;21;101;31;37 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. L33S, which was originally reported as a C34 resistance associated mutation, significantly enhanced resistance in the background of N43D/S138A mutations (HIV-1L33S/N43D/S138A). 2013 The international journal of biochemistry & cell biology Result HIV L33S;N43D;S138A;N43D;S138A;L33S 159;164;169;132;137;0 163;168;174;136;142;4 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. MT-2 cells were infected with HIV-1WT and HIV-1N43D/S138A, and incubated in the presence of T-20S138A at the initial concentrations of 0.1 nM and 1 nM, respectively. 2013 The international journal of biochemistry & cell biology Result HIV S138A;S138A 96;52 101;57 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. N126K conferred only marginal resistance (<3-fold) to all peptide fusion inhibitors, but in the background of I37N (HIV-1I37N/N126K) it enhanced resistance to T-20, T-20S138A, and C34. 2013 The international journal of biochemistry & cell biology Result HIV I37N;I37N;N126K;N126K 121;110;126;0 125;114;131;5 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. On the other hand, in the selection with T-20-resistant HIV-1N43D/S138A. 2013 The international journal of biochemistry & cell biology Result HIV S138A 66 71 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. On the other hand, T-20E137K/S138A (Table 2) maintained some antiviral activity against HIV-1L33S/N43D/S138A, HIV-1L33S/N43D/E137K/S138A, and HIV-1I37N/L44M/N126K compared with other T-20 derivatives including electrostatically constrained T-20EK (Tables 1and. 2013 The international journal of biochemistry & cell biology Result HIV E137K;L44M;N126K;N43D;N43D;S138A;S138A;S138A 125;152;157;98;120;103;131;29 130;156;162;102;124;108;136;34 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Other mutations, L44M, I69L, and E137K, which were observed in wild-type HIV-1 as polymorphisms, conferred little resistance to all peptide fusion inhibitors tested. 2013 The international journal of biochemistry & cell biology Result HIV E137K;I69L;L44M 33;23;17 38;27;21 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Recently, we demonstrated that introduction of the S138A secondary mutation to T-20 (T-20S138A) enhanced binding to mutated N-HR and suppresses resistance of T-20-resistance variants. 2013 The international journal of biochemistry & cell biology Result HIV S138A 51 56 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Selected mutations I37N and L33S provided various levels of resistance to T-20 and its derivatives, T-20S138A and T-20EK, apparently acting as primary mutations to peptides with a T-20 backbone (Table 1). 2013 The international journal of biochemistry & cell biology Result HIV I37N;L33S 19;28 23;32 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Similar to the N126K mutation, E137K also enhanced resistance by N43D/S138A (HIV-1N43D/E137K/S138A) and L33S/N43D/S138A (HIV-1L33S/N43D/E137K/S138A) to T-20S138A, T-20, and T-20EK. 2013 The international journal of biochemistry & cell biology Result HIV L33S;N43D;E137K;E137K;L33S;N43D;N43D;S138A;S138A;S138A;S138A;E137K;N126K;N43D;S138A 126;82;87;136;104;109;131;93;114;142;156;31;15;65;70 130;86;92;141;108;113;135;98;119;147;161;36;20;69;75 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Similarly, as shown in Figure 3, E137K enhanced binding affinity with N-HR, suggesting that introduction of E137K to T-20 may enhance the antiviral activity of T-20. 2013 The international journal of biochemistry & cell biology Result HIV E137K;E137K 33;108 38;113 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Similarly, S138A and E137K/S138A restored the binding affinity of C34 to N36N43D. 2013 The international journal of biochemistry & cell biology Result HIV E137K;S138A;S138A 21;11;27 26;16;32 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Since in vitro T-20 does not interact with the N36 peptide (amino acid positions 35-70 of the N-HR), we used instead peptide C34 with E137K and/or S138A substitutions. 2013 The international journal of biochemistry & cell biology Result HIV E137K;S138A 134;147 139;152 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. The emergence of the I69L mutation in diverse HIV-1 strains has been previously reported. 2013 The international journal of biochemistry & cell biology Result HIV I69L 21 25 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. The S138A mutation restored the replication kinetics of HIV-1N43D. 2013 The international journal of biochemistry & cell biology Result HIV S138A 4 9 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Therefore, we examined the viral replication kinetics of mutants with LTTG44LCTG, and compared HIV-1WT, with HIV-1L44L-CTG, and HIV-1L33S/N43D/L44L-CTG/E137K/S138A with HIV-1L33S/N43D/L44L-CTG/I69L/E137K/S138A. 2013 The international journal of biochemistry & cell biology Result HIV L33S;L33S;E137K;E137K;I69L;L44L;L44L;N43D;N43D;S138A;S138A 133;174;152;198;193;143;184;138;179;158;204 137;178;157;203;197;147;188;142;183;163;209 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. These results indicate that E137K acts as a compensatory mutation for the T-20S138A-resistance primary mutation, causing enhancement of replication kinetics. 2013 The international journal of biochemistry & cell biology Result HIV S138A;E137K 78;28 83;33 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. These results indicate that even though T-20S138A was active against T-20 resistant variants, resistant HIV-1 emerged relatively rapidly compared with the next generation fusion inhibitors, such as SC34EK, which required 120 passages to acquire the resistance. 2013 The international journal of biochemistry & cell biology Result HIV S138A 44 49 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. These results indicate that L33S and I37N appear to be primary mutations for T-20 derivatives. 2013 The international journal of biochemistry & cell biology Result HIV I37N;L33S 37;28 41;32 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. These results indicate that the primary mutation, L33S, possesses less ability to attenuate HIV-1 replication, while I69L, S138A, and E137K enhance replication kinetics of T-20-resistant HIV-1 to a comparable level of HIV-1WT. 2013 The international journal of biochemistry & cell biology Result HIV E137K;I69L;L33S;S138A 134;117;50;123 139;121;54;128 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. This was consistent with previous studies that also reported a resistance enhancement (1.8-fold) by L44M to T-20. 2013 The international journal of biochemistry & cell biology Result HIV L44M 100 104 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. To address the effects of mutations on HIV-1 replication, we examined the replication kinetics of T-20S138A-resistant HIV-1N43D/S138A variants. 2013 The international journal of biochemistry & cell biology Result HIV S138A 128 133 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. To clarify the effect of E137K substitutions on peptide binding, we examined the binding affinities of E137K-containing C-HR peptides to N-HR using CD analysis. 2013 The international journal of biochemistry & cell biology Result HIV E137K;E137K 25;103 30;108 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We found that mixtures of C34E137K, C34S138A, or C34E137K/S138A with N36 or N36N43D showed sufficient and comparable alpha-helicity at 25 C. 2013 The international journal of biochemistry & cell biology Result HIV E137K;S138A 52;58 57;63 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We synthesized T-20 and T-20S138A variants containing the E137K change (T-20E137K and T-20E137K/S138A). 2013 The international journal of biochemistry & cell biology Result HIV E137K;S138A 58;96 63;101 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. But the D25K mutation associated with phenotypic switch in FF94 was absent, supporting evolution to CXCR4-use in vivo. 2013 Retrovirology Result HIV D25K 8 12 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Envelope sequence analysis revealed that, in contrast with FD83, five of eight clones amplified from the lymph node of EN31 at the time of necropsy harbored arginine at position 11 of the V3 loop (S11R), while those in FF94 had, at position 25, either lysine (D25K; 23 of 24 clones) or arginine (D25R; 1 of 24 clones) residue (Figure 4A). 2013 Retrovirology Result HIV D25K;D25R;S11R 260;296;197 264;300;201 Env 0 8 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Functional assays showed that in contrast with Envs bearing WT V3 sequence that use only CCR5 for entry, Envs harboring V3 S11R (EnvS11R) or D25K mutation (EnvD25K) were dual-tropic, infecting U87.CD4 cells that expressed either the CCR5 or CXCR4 coreceptor (Figure 4B). 2013 Retrovirology Result HIV D25K 141 145 Env;Env;Env;Env 47;105;129;156 51;109;132;159 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. In contrast, the D25K variant co-existed with R5 viruses in the plasma at all time points analyzed. 2013 Retrovirology Result HIV D25K 17 21 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Interestingly, deep sequencing of gp120 V3 in the clone 11 inoculum (21,048 reads) revealed presence of the S11R mutation at very low frequency (0.07%), raising the possibility of X4 evolution during clone expansion in vitro. 2013 Retrovirology Result HIV S11R 108 112 gp120 34 39 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. S11R substitutions as a result of a single nucleotide point mutation were also detected in the SHIVSF162P3N clone 8 virus stock (0.11%; 37,360 reads). 2013 Retrovirology Result HIV S11R 0 4 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. The D25K variant was not detectable in the blood by clonal sequence at 46 and 50 wpi, emerging in plasma and PBMCs sampled four weeks later. 2013 Retrovirology Result HIV D25K 4 8 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. We found that the dual-tropic D25K V3 variant was detected by clonal analysis at low frequency (1 of 21 clones sequenced) in the Ing LN of FF94 sampled at 46 wpi. 2013 Retrovirology Result HIV D25K 30 34 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. A43D (31), a BA derivative with a C28 modified side chain but without the C3 side chain of 1, was used as a positive control for inhibition of HIV-1 entry. 2013 Journal of medicinal chemistry Result HIV A43D 0 4 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. Activity of Compound 1 Derivatives against BVM-R HIV-1 Variant V370A. 2013 Journal of medicinal chemistry Result HIV V370A 63 68 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. As expected, 1 interfered with the cleavage of Gag CA-SP1 in wild type NL4-3 as shown by p25 accumulation, but did not inhibit the cleavage of Gag CA-SP1 in the drug resistant variant NL4-3/V370A under the same experimental conditions (Figure 2a). 2013 Journal of medicinal chemistry Result HIV V370A 190 195 SP1;SP1;Gag;Gag;Capsid;Capsid 54;150;47;143;51;147 57;153;50;146;53;149 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. As expected, 1 potently inhibited wild type NL4-3 with an IC50 of 0.076 muM, but was ineffective at up to 6.8 muM against the BVM-R variant NL4-3/V370A. 2013 Journal of medicinal chemistry Result HIV V370A 146 151 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. Compound 6 with a C28 methyl nonanoyl-glutaminate side chain, exhibited the best anti-HIV potency against both wild type virus and the BVM-R NL4-3/V370A variant with IC50 values of 0.01 and 0.16 muM, respectively. 2013 Journal of medicinal chemistry Result HIV V370A 147 152 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. In contrast to 1, most of the new C28 modified analogs exhibited inhibitory activity against the BVM-R NL4-3/V370A variant with IC50 values less than 3 muM. 2013 Journal of medicinal chemistry Result HIV V370A 109 114 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. NL4-3 and the BVM-R variant NL4-3/V370A were produced by 293T cells in the presence of 1 or 6. 2013 Journal of medicinal chemistry Result HIV V370A 34 39 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. On the other hand, treatment of the BVM-R NL4-3/V370A virus with 6 resulted in accumulation of CA-SP1 (p25), the signature event of inhibition of HIV-1 maturation. 2013 Journal of medicinal chemistry Result HIV V370A 48 53 SP1;Capsid 98;95 101;97 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. The accumulation of p25 was even more pronounced when the BVM-R NL4-3/V362I virus was produced in the presence of 6 (Figure 2b). 2013 Journal of medicinal chemistry Result HIV V362I 70 75 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. The rank order of sensitivity of the BVM-R variants to 6 was NL4-3/V362I > NL4-3/T371Delta > NL4-3/V370A > NL4-3/V370Delta. 2013 Journal of medicinal chemistry Result HIV V362I;V370A 67;99 72;104 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. The synthesized compounds were tested initially against both the wild type HIV-1 NL4-3 and NL4-3/V370A, a variant that carries the most prevalent BVM-R polymorphism with an Ala at position 370 in the SP1 region. 2013 Journal of medicinal chemistry Result HIV V370A 97 102 SP1 200 203 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. This was consistent with the anti-viral results that NL4-3/V362I was most sensitive to 6 among the BVM-R mutants. 2013 Journal of medicinal chemistry Result HIV V362I 59 64 23379607 New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. While these viruses were not sensitive to 1 (Table 4), all four BVM-R variants with V370Delta, V370A, V362I, and T371Delta polymorphisms were sensitive to 6. 2013 Journal of medicinal chemistry Result HIV V362I;V370A 102;95 107;100 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. Clinically significant efavirenz resistance was conferred by the rtK103N mutation. 2012 Annals of Saudi medicine Result HIV K103N 67 72 RT 65 67 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. The most common mutation (found in 71% of strains) was piM36I (Table 2). 2012 Annals of Saudi medicine Result HIV M36I 55 61 PI 55 57 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. The rtM184V mutation was present in 70% of strains and was associated with cross-resistance to at least two NRTIs:lamivudine and emtricitabine (Table 3). 2012 Annals of Saudi medicine Result HIV M184V 6 11 NRTI;RT 108;4 113;6 23401688 Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil. K103N/S (53%, 9/17) was the most frequent mutation observed. 2013 Advances in virology Result HIV K103S;K103N 0;0 7;7 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. A comparison of wild-type IN (Figure 4A) to H51Y IN (Figure 4B) revealed no significant differences in secondary structure; however, a comparison of wild-type to R263K (Figure 4C) and H51Y/R263K (Figure 4D) demonstrated incremental disruptions in orientation of R262 and K264 that may contribute to viral DNA interactions , resulting in a larger scale disruption of electrostatic interactions in the C-terminus of integrase, which are transferred to key residues involved in INSTI drug resistance. 2013 Retrovirology Result HIV H51Y;H51Y;R263K;R263K 45;187;164;192 49;191;169;197 IN;INSTI;IN;IN 418;479;26;50 427;484;28;52 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Additionally, in the case of both R263K and H51Y/R263K, the orientation of the residue at position 51 is inverted (Figure 4C and 4D), which may have an impact on HIV-1 DNA binding ability, explaining the loss in fitness of the R263K and H51Y/R263K viruses. 2013 Retrovirology Result HIV H51Y;H51Y;R263K;R263K;R263K;R263K 44;238;34;49;228;243 48;242;39;54;233;248 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Although the single mutations modestly diminished HIV replication, the H51Y/R263K combination resulted in a dramatic impairment of viral infectivity (Figure 2A) and viral fitness (Figure 2B). 2013 Retrovirology Result HIV H51Y;R263K 71;76 75;81 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Both H51Y and R263K individually conferred low-level resistance to EVG (2.06 and 3.28-fold, respectively) while the combination dramatically increased the IC50 for this drug by 41.5-fold. 2013 Retrovirology Result HIV H51Y;R263K 5;14 9;19 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Docking of DTG to the model active sites showed favorable binding in all active sites, albeit with reduced apparent affinity in the R263K and H51Y/R263K models. 2013 Retrovirology Result HIV H51Y;R263K;R263K 142;132;147 146;137;152 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In agreement with our biochemical results, we found that the H51Y mutation had no effect on HIV integration. 2013 Retrovirology Result HIV H51Y 61 65 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In contrast, the R263K mutation and the H51Y/R263K combination were associated with decreased integration, similar to the reduced enzymatic activity measured with the purified mutated recombinant integrase proteins. 2013 Retrovirology Result HIV H51Y;R263K;R263K 40;17;45 44;22;50 IN 196 205 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In silico studies of H51Y mutant integrase. 2013 Retrovirology Result HIV H51Y 21 25 IN 33 42 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In this assay, R263K conferred low-level resistance to DTG (~2-fold) and the addition of H51Y to R263K further increased HIV resistance to ~7-fold. 2013 Retrovirology Result HIV H51Y;R263K;R263K 89;15;97 93;20;102 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. INWT, INH51Y, INR263K, and INH51Y/R263K at varying concentrations (Figure 1A and B) showed that INWT and INH51Y had comparable maximal strand transfer activity (100+-3.7% and 107.7+-10.7%, respectively) whereas INH51Y/R263K maximal activity was severely diminished (20.01+-2.9%). 2013 Retrovirology Result HIV R263K;R263K 34;219 39;224 IN;IN;IN;IN;IN 6;14;27;106;212 8;16;29;108;214 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Notably, the fold change in RAL susceptibility observed with H51Y (1.2-fold) was not significant in our experiments but was identical to results from another study . 2013 Retrovirology Result HIV H51Y 61 65 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Now, by introducing the H51Y mutation alone or in combination with R263K into pNL4.3 proviral DNA, we show that the combination of H51Y and R263K increased resistance to DTG (FC=16.5-fold), whereas H51Y alone did not confer resistance to this drug (Table 1). 2013 Retrovirology Result HIV H51Y;H51Y;H51Y;R263K;R263K 24;131;198;67;140 28;135;202;72;145 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Our previous work showed that the primary resistance mutation R263K decreased integrase activity in cell-free assays . 2013 Retrovirology Result HIV R263K 62 67 IN 78 87 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. pNL4.3IN(WT), pNL4.3IN(H51Y), pNL4.3IN(R263K), and pNL4.3IN(H51Y/R263K) (Figure 2). 2013 Retrovirology Result HIV H51Y;H51Y;R263K;R263K 23;60;39;65 27;64;44;70 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Similar experiments with RAL showed that the combination of both mutations conferred low-level resistance to this drug (2.1-fold, Table 1) while the individual H51Y and R263K mutations were innocuous. 2013 Retrovirology Result HIV H51Y;R263K 161;170 165;175 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Since levels of drug resistance can vary depending on differences in assays or target cells, HIV susceptibility to RAL, EVG, and DTG was also tested in viruses containing the H51Y and R263K mutations using the PhenoSense Integrase phenotypic assay (Monogram Biosciences) (Table 2). 2013 Retrovirology Result HIV H51Y;R263K 175;184 179;189 IN 222 231 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. The addition of H51Y to R263K decreases HIV integration. 2013 Retrovirology Result HIV H51Y;R263K 16;24 20;29 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. The addition of H51Y to R263K decreases HIV replication capacity. 2013 Retrovirology Result HIV H51Y;R263K 16;24 20;29 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. The addition of H51Y to R263K decreases integrase strand-transfer activity. 2013 Retrovirology Result HIV H51Y;R263K 16;24 20;29 IN 40 49 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. The addition of H51Y to R263K increases resistance against dolutegravir. 2013 Retrovirology Result HIV H51Y;R263K 16;24 20;29 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. The negative effect of the H51Y/R263K combination on HIV replication capacity was also observed in the PhenoSense integrase replication assay (Table 2). 2013 Retrovirology Result HIV H51Y;R263K 27;32 31;37 IN 115 124 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. The sequential addition of R263K and the H51Y/R263K mutations resulted in an incremental loss in enzyme activity, while the effect of H51Y alone was innocuous. 2013 Retrovirology Result HIV H51Y;H51Y;R263K;R263K 41;134;27;46 45;138;32;51 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. These mutations tested individually had no impact on HIV susceptibility to RAL whereas the H51Y/R263K combination conferred an approximate 3-fold resistance to this compound. 2013 Retrovirology Result HIV H51Y;R263K 91;96 95;101 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. To determine whether the observed defect in HIV replication capacity conferred by the R263K and H51Y mutations was due to a decrease of HIV DNA integration, we used an Alu-mediated qPCR assay to monitor integration in primary human peripheral blood mononuclear cells (PBMCs) infected with pNL4.3IN(WT), pNL4.3IN(H51Y), pNL4.3IN(R263K), and pNL4.3IN(H51Y/R263K) (Figure 3). 2013 Retrovirology Result HIV H51Y;H51Y;H51Y;R263K;R263K;R263K 96;312;349;86;328;354 100;316;353;91;333;359 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. To gain insight into the effect of the H51Y and R263K mutations on susceptibility to DTG, we performed structural modeling of HIV integrase in the presence of each mutation alone and in combination. 2013 Retrovirology Result HIV H51Y;R263K 39;48 43;53 IN 130 139 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Together with our biochemical results, these data suggest that the H51Y mutation does not compensate for the primary resistance mutation R263K but rather has an additional detrimental effect on viral fitness when R263K is present. 2013 Retrovirology Result HIV H51Y;R263K;R263K 67;137;214 71;142;219 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. We have previously shown and confirm here that the unique R263K mutation confers low-level resistance ( 10-fold) to DTG (Table 1) . 2013 Retrovirology Result HIV R263K 58 63 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Another interesting observation is that mutations Y188C and G190A are predicted to render HIV more sensitive to Etravirine according to our model. 2013 PLoS computational biology Result HIV G190A;Y188C 60;50 65;55 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Both in internal validation and validation on unseen data our model showed performance comparable to assay reliability and better than sequence only models; moreover, model interpretation has been performed to identify novel resistance-conferring mutations that lead to resistance to all drugs in a class, such as T216M in the case of RT. 2013 PLoS computational biology Result HIV T216M 314 319 RT 335 337 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Finally, N88G seems to only be sensitive to Darunavir, while conferring resistance to all other PIs in the dataset. 2013 PLoS computational biology Result HIV N88G 9 13 PI 96 99 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. For instance, mutation K103N has a rather specific pattern as it confers resistance to Nevirapine, Efavirenz, and Delavirdine but not to Etravirine. 2013 PLoS computational biology Result HIV K103N 23 28 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. For instance, the G48W mutant is sensitive to Darunavir and Tipranavir, while showing some degree of resistance to all other PIs. 2013 PLoS computational biology Result HIV G48W 18 22 PI 125 128 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. For the PIs mutations that are accurately reproduced include D30N, I50L, V82S, and I84, while the I64L and I93M mutations are assigned less importance than in previous work. 2013 PLoS computational biology Result HIV D30N;I50L;I64L;I93M;V82S 61;67;98;107;73 65;71;102;111;77 PI 8 11 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Furthermore, R87K is resistant to Atazanavir, Darunavir, and Tipranavir, but sensitive to all other drugs in the dataset. 2013 PLoS computational biology Result HIV R87K 13 17 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Furthermore, V179F is known to lead to Etravirine resistance but to have less effect on Nevirapine, Efavirenz, and Delavirdine, a resistance profile that can also be reproduced based on our dataset. 2013 PLoS computational biology Result HIV V179F 13 18 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. In addition, we can use these models to find mutations that lead specific sensitivity (G48W in PR) or resistance (G68R in PR) to a single drug within a class. 2013 PLoS computational biology Result HIV G48W;G68R 87;114 92;119 PR;PR 95;122 97;124 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Mutations identified have a high impact on drug affinity and which lend themselves to experimental validation, for instance in the case of NNRTI and NRTI resistance conferring mutation T216M. 2013 PLoS computational biology Result HIV T216M 185 190 NNRTI;NRTI 139;149 144;153 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Reference 789 contained a sequence carrying a deletion at position 69, which was not taken into account by our model. 2013 PLoS computational biology Result HIV del 69 46 69 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. References 369, 414, 649 all contained the M184V and T215Y mutations that are also known to differ between AVG and Phenosense. 2013 PLoS computational biology Result HIV M184V;T215Y 43;53 48;58 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Some mutations are slightly underestimated, these include V90I and V106I. 2013 PLoS computational biology Result HIV V106I;V90I 67;58 72;62 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Specific NRTI mutations that were accurately reproduced include K65R, Q151M, and T215Y, while mutations M41L and M184V are slightly underestimated, compared to previous studies. 2013 PLoS computational biology Result HIV K65R;M184V;M41L;Q151M;T215Y 64;113;104;70;81 68;118;108;75;86 NRTI 9 13 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. As expected, among the NRTI and NNRTI mutations, M184I/V (71.9%), T215Y/F (34.4%), K103N (34.3%), and Y181C (28.1%) were the most prevalent in any of the compartments. 2013 Journal of the International AIDS Society Result HIV K103N;M184I;M184V;T215F;T215Y;Y181C 83;49;49;66;66;102 88;56;56;73;73;107 NNRTI;NRTI 32;23 37;27 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. In one patient with hypermutated sequence, M184I was observed in the proviral sequence but not in plasma. 2013 Journal of the International AIDS Society Result HIV M184I 43 48 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. In two proviral sequences only, the E138K mutation was observed. 2013 Journal of the International AIDS Society Result HIV E138K 36 41 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. M184V and T215Y/F were observed in plasma only in six and three patients, respectively, while M41L and K65R were observed in one patient each in provirus only. 2013 Journal of the International AIDS Society Result HIV K65R;M41L;T215F;T215Y;M184V 103;94;10;10;0 107;98;17;17;5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. One patient had D67DN and K70KE mutations in the proviral sequence. 2013 Journal of the International AIDS Society Result HIV D67D;D67N;K70E;K70K 16;16;26;26 21;21;31;31 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. The three hypermutated proviral sequences from the therapy naive patients who had M184I and M230I drug resistance mutations and mutation in drug resistance position (M41I) also had stop codons in the RT ORF particularly at the tryptophan residue, which is the target site for hA3G. 2013 Journal of the International AIDS Society Result HIV M184I;M230I;M41I 82;92;166 87;97;170 RT 200 202 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. A base substitution hot spot at position -36 was observed in the mutational spectra of O_D443N and O_E478Q RTs. 2013 Nucleic acids research Result HIV D443N;E478Q 89;101 94;106 RT 107 110 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. All RNase H-deficient RTs were shown to introduce large deletions, although they were more frequent in the case of mutant O_E478Q. 2013 Nucleic acids research Result HIV E478Q 124 129 RT 22 25 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. All tested RTs showed similar or increased catalytic efficiencies (measured as the ratio kcat/Km) in comparison with the O_WT RT, and the mutant enzyme V75I (O_V75I), as well as with the BH10_WT RT. 2013 Nucleic acids research Result HIV V75I;V75I 152;160 156;164 RT;RT;RT 11;126;195 14;128;197 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Although position +149 could be considered as a common hot spot location for both mutant RTs, identified errors were one-nucleotide deletions in the case of O_V75I/D443N RT and base substitutions (mostly G T mutations) in the case of O_V75I/E478Q RT. 2013 Nucleic acids research Result HIV D443N;E478Q;V75I;V75I 164;241;159;236 169;246;163;240 RT;RT;RT 89;170;247 92;172;249 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. BH10_E478Q RT has a low tendency to produce large deletions. 2013 Nucleic acids research Result HIV E478Q 5 10 RT 11 13 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. D443N or E478Q) were devoid of endonuclease activity, as determined with an RNA/DNA heteropolymeric substrate (Figure 2). 2013 Nucleic acids research Result HIV E478Q;D443N 9;0 14;5 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. For example, the base substitution error rate of O_E478Q RT was estimated to be 10.9 times lower than the rate obtained with the O_WT enzyme. 2013 Nucleic acids research Result HIV E478Q 51 56 RT 57 59 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. For example, the spectrum of O_D443N RT has one hot spot at position +123, and O_V75I/D443N has four major hot spots for one-nucleotide deletions at positions -61, +105, +141 and +149. 2013 Nucleic acids research Result HIV D443N;D443N;V75I 86;31;81 91;36;85 RT 37 39 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Hotspots around positions +105/+106 and +149 were found in the spectra of O_V75I/D443N and O_V75I/E478Q RTs. 2013 Nucleic acids research Result HIV D443N;E478Q;V75I;V75I 81;98;76;93 86;103;80;97 RT 104 107 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. However, in contrast with the well-known strong tendency to produce -1 frameshifts of WT HIV-1 group M subtype B RTs, this type of errors represented only 11.2% of all identified mutations in the spectrum of the BH10_E478Q RT (Table 3 and Supplementary Figure S2e). 2013 Nucleic acids research Result HIV E478Q 217 222 RT;RT 113;223 116;225 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In contrast, the wild-type enzyme showed increased frameshift fidelity in comparison with mutant O_E478Q RT. 2013 Nucleic acids research Result HIV E478Q 99 104 RT 105 107 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In the case of BH10 RT, the increased fidelity conferred by E478Q could be also attributed to its lower base substitution error rate, as compared with the BH10_WT RT (Table 3). 2013 Nucleic acids research Result HIV E478Q 60 65 RT;RT 20;163 22;165 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Interestingly, these values correlate well with the calculated frameshift error rates that are highest for mutant O_V75I/D443N RT and lowest for O_WT and O_V75I RTs. 2013 Nucleic acids research Result HIV D443N;V75I;V75I 121;116;156 126;120;160 RT;RT 127;161 129;164 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. mixtures of three nucleotides) showed that HIV-1 group O RNase H-deficient RTs, such as mutants D443N and V75I/E478Q, rendered shorter products than the WT enzyme (Supplementary Figure S1). 2013 Nucleic acids research Result HIV D443N;E478Q;V75I 96;111;106 101;116;110 RT 75 78 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Mutants O_D443N and O_V75I/D443N showed a higher tendency to introduce -1 frameshifts at heteropolymeric sequences. 2013 Nucleic acids research Result HIV D443N;D443N;V75I 27;10;22 32;15;26 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Mutational hot spots generated by BH10_E478Q RT, and involving base substitutions at positions -36, +81/+83 and +88/+90 were also observed in the mutational spectrum of BH10_WT RT. 2013 Nucleic acids research Result HIV E478Q 39 44 RT;RT 45;177 47;179 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Mutations E478Q and D443N showed the largest increase in accuracy when introduced in the O_WT RT sequence context. 2013 Nucleic acids research Result HIV D443N;E478Q 20;10 25;15 RT 94 96 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. non-runs) in comparison with the RTs containing the E478Q substitution. 2013 Nucleic acids research Result HIV E478Q 52 57 RT 33 36 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. O_V75I, O_V75I/D443N and O_V75I/E478Q) showed intermediate processivity, while O_D443N RT and particularly O_E478Q were found to be the least processive polymerases. 2013 Nucleic acids research Result HIV D443N;D443N;E478Q;E478Q;V75I;V75I;V75I 15;81;32;109;2;10;27 20;86;37;114;6;14;31 Pol;RT 153;87 164;89 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Similar data were obtained with O_D443N RT, which in comparison with the WT RT introduced base substitutions errors with an 8.3-fold reduced frequency, but showed increased frameshift error rate. 2013 Nucleic acids research Result HIV D443N 34 39 RT;RT 40;76 42;78 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Termination sites appear to be similar for all enzymes, but prominent stops were observed at position +102 with mutants O_D443N and O_E478Q. 2013 Nucleic acids research Result HIV D443N;E478Q 122;134 127;139 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The calculated error rates reveal that both D443N and E478Q increase the accuracy of the RT by reducing the base substitution error rate, although both mutant RTs also showed decreased frameshift fidelity. 2013 Nucleic acids research Result HIV D443N;E478Q 44;54 49;59 RT;RT 89;159 91;162 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The mutant frequencies obtained with HIV-1 group O RTs lacking RNase H activity, such as mutants O_D443N, O_E478Q, O_V75I/D443N and O_V75I/E478Q, were ~3-6.6 times lower than those obtained with the wild-type enzyme (Table 2). 2013 Nucleic acids research Result HIV D443N;D443N;E478Q;E478Q;V75I;V75I 122;99;139;108;117;134 127;104;144;113;121;138 RT 51 54 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The mutant O_V75I/D443N showed the highest koff, followed by the RTs O_D443N, O_V75I/E478Q and O_E478Q, while the lowest koff values were obtained with the WT enzyme and the mutant O_V75I RT. 2013 Nucleic acids research Result HIV D443N;D443N;E478Q;E478Q;V75I;V75I;V75I 18;71;85;97;13;80;183 23;76;90;102;17;84;187 RT;RT 65;188 68;190 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The substitution D443N produced a moderate increase in DNA polymerase activity that in the case of the double-mutant V75I/D443N was due in part to the higher kcat value obtained with this enzyme. 2013 Nucleic acids research Result HIV D443N;D443N;V75I 17;122;117 22;127;121 Pol 59 69 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The three RTs having the mutation V75I. 2013 Nucleic acids research Result HIV V75I 34 38 RT 10 13 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. These effects were also observed in the BH10 RT, as the corresponding E478Q mutant showed 2-fold increased fidelity in comparison with the wild-type enzyme (Table 2). 2013 Nucleic acids research Result HIV E478Q 70 75 RT 45 47 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. These results were rather different from those obtained with O_WT and mutant O_V75I RTs that showed a very low tendency to introduce insertions or deletions. 2013 Nucleic acids research Result HIV V75I 79 83 RT 84 87 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. This mutational hot spot was previously identified in the mutational analysis of O_WT and O_V75I RTs, but was absent in the RNase H-deficient polymerases carrying the V75I substitution. 2013 Nucleic acids research Result HIV V75I;V75I 167;92 171;96 Pol;RT 142;97 153;100 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Unlike in the case of O_WT and O_V75I RTs, insertions and deletions represented 30-68% of all errors in the mutational spectra generated by the RNase H-deficient HIV-1 group O RTs (Table 3). 2013 Nucleic acids research Result HIV V75I 33 37 RT;RT 38;176 41;179 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Accordingly, transduction of lymphocytes and macrophages by V86M HIV-1 was significantly affected by treatment by 5 muM of cyclosporine A (CsA), a drug that competes with CA for binding to CypA (Additional file 1: Figure S1). 2013 Retrovirology Result HIV V86M 60 64 Capsid 171 173 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. All the cell lines created were challenged by wild-type (WT) or V86M HIV-1 NL43-based vectors (Figure 1). 2013 Retrovirology Result HIV V86M 64 68 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Also, the level of rescue of HIV-1NL-GFP infectivity by either V86M mutation or CsA treatment was grossly proportional to the level of restriction. 2013 Retrovirology Result HIV V86M 63 67 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Altogether, data in Figures 2 and 3 show that restriction of V86M HIV-1 replication by R332G-R335G TRIM5alphahu is poorly sensitive to the presence of CypA compared to restriction of the WT control. 2013 Retrovirology Result HIV R332G;R335G;V86M 87;93;61 92;98;65 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Altogether, this experiment shows that restriction of a spreading HIV-1 infection by mutant TRIM5alphahu in Sup-T1 cells is enhanced by CypA, and suggests that the V86M mutation does not rescue HIV-1 replication in this context. 2013 Retrovirology Result HIV V86M 164 168 HIV infections 66 81 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. As expected, accumulation of HIV-1 DNA was reduced in cells expressing TRIM5alpharh and R332G-R335G TRIM5alphahu, and levels of nuclear HIV-1 DNA were even more strongly decreased. 2013 Retrovirology Result HIV R332G;R335G 88;94 93;99 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. CA-V86M HIV-1 is partially resistant to restriction by TRIM5alphahu mutant R332G-R335G. 2013 Retrovirology Result HIV R332G;R335G;V86M 75;81;3 80;86;7 Capsid 0 2 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. CsA rescued replication of WT HIV-1NL-GFP in cells expressing R332G-R335G TRIM5alphahu, by up to 6-fold in TE671 cells and 8-fold in Sup-T1 cells. 2013 Retrovirology Result HIV R332G;R335G 62;68 67;73 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. CypA knockdown enhanced infectivity of WT HIV-1NL-GFP by 5-fold in TE671 cells and by 3-fold in Sup-T1 cells, but had no significant effect on the replication of the V86M mutant. 2013 Retrovirology Result HIV V86M 166 170 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Data in Figures 1, 2, 3, 4 and 5 showed that V86M made HIV-1 resistant to CypA-dependent, TRIM5alpha-mediated restriction mechanisms. 2013 Retrovirology Result HIV V86M 45 49 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Data shown in Figures 1 and 2 revealed that restriction of HIV-1 by R332G-R335G TRIM5alphahu was counteracted either by the V86M mutation or by CsA treatment, and suggested that the two interventions had redundant effects. 2013 Retrovirology Result HIV R332G;R335G;V86M 68;74;124 73;79;128 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Effect of CypA and V86M on a spreading HIV-1 infection. 2013 Retrovirology Result HIV V86M 19 23 HIV infections 39 54 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Effects of V86M on early stages of viral replication. 2013 Retrovirology Result HIV V86M 11 15 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. For the V86M capsid, the exchange rate for the major G89 peak was ~20 s-1. 2013 Retrovirology Result HIV V86M 8 12 Capsid 13 19 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Furthermore, there is evidence of a second minor G89cis peak in the V86M spectra that is indicative of discrete CypA-binding loop isomers. 2013 Retrovirology Result HIV V86M 68 72 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. G330E, R332G, R335G, and G330E-R332G-R335G TRIM5alphahu all restricted HIV-1 when expressed in TE671 cells, albeit with various efficacies (Additional file 1: Figure S3A), and as shown before. 2013 Retrovirology Result HIV G330E;R332G;R332G;R335G;R335G;G330E 25;7;31;14;37;0 30;12;36;19;42;5 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, in the V86M mutant, at least two cis exchange peaks were observed compared to a single peak in the WT. 2013 Retrovirology Result HIV V86M 16 20 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, replication of V86M HIV-1 in permissive human cells is as much sensitive as WT HIV-1 to the presence of CypA. 2013 Retrovirology Result HIV V86M 24 28 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, the peak positions for both states in V86M were chemically shifted compared to WT, suggesting that the mutation influences the conformations adopted by the cyclophilin-binding loop (Figure 6A). 2013 Retrovirology Result HIV V86M 47 51 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, the slope of the linear curve (1.89) also shows that CsA is more efficient than V86M at rescuing HIV-1 replication. 2013 Retrovirology Result HIV V86M 89 93 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, V86M 2-LTR DNA levels in restrictive cells were still reduced 5- to 10-times compared with levels of WT 2-LTR DNA in non-restrictive conditions, as expected from the observation that V86M only partially rescues HIV-1 in restrictive conditions. 2013 Retrovirology Result HIV V86M;V86M 9;192 13;196 LTR;LTR 16;115 19;118 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. However, V86M HIV-1NL-GFP was about 4-times more infectious than its WT counterpart in cells expressing R332G-R335G TRIM5alphahu, and this was true in all the three cell lines tested (Figure 1). 2013 Retrovirology Result HIV R332G;R335G;V86M 104;110;9 109;115;13 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In cells expressing R332G TRIM5alphahu, active replication was detected but only at a single time-point (day 35 post-infection). 2013 Retrovirology Result HIV R332G 20 25 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In contrast, the impact of the drug on the restriction of the V86M mutant by this variant of TRIM5alphahu was much smaller: up to 1.5-fold and 2-fold in TE671 and Sup-T1 cells, respectively. 2013 Retrovirology Result HIV V86M 62 66 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In control permissive cells, replication of both WT and V86M HIV-1NL-GFP was decreased (25 to 35%) either by expression of the CypA shRNA or by CsA treatment (Figures 2A and 2B, left panels). 2013 Retrovirology Result HIV V86M 56 60 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In order to better characterize the role of CypA in the TRIM5alpha resistance conferred by V86M, we analyzed the effect of this mutation on other mutants of TRIM5alphahu. 2013 Retrovirology Result HIV V86M 91 95 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In order to investigate the role of CypA and the effect of V86M on HIV-1 restriction in a spreading infection context, we infected Sup-T1 cells with the NL4-3 strain of HIV-1 (Figure 8). 2013 Retrovirology Result HIV V86M 59 63 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In other words, restriction of V86M HIV-1NL-GFP was 4-times less efficient than restriction of WT HIV-1NL-GFP. 2013 Retrovirology Result HIV V86M 31 35 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In shRNA-CypA/R332G-R335G TRIM5alphahu-expressing cells, replication of both WT and V86M NL4-3 was detected, although at low levels. 2013 Retrovirology Result HIV R332G;R335G;V86M 14;20;84 19;25;88 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In TE671 and Sup-T1 cells expressing R332G-R335G TRIM5alphahu, replication of WT HIV-1 was strongly reduced compared with the control "vector" cells (~50-fold and 20-fold, respectively) and like before, V86M partly rescued infection of HIV-1 in these cells (5-fold in TE671 cells, 2.5-fold in Sup-T1 cells). 2013 Retrovirology Result HIV R332G;R335G;V86M 37;43;203 42;48;207 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In the absence of CypA, we observed two G89 N-H correlation peaks in the V86M capsid spectra, indicating that, as in WT, the GP bond exists in both cis and trans states. 2013 Retrovirology Result HIV G89N;V86M 40;73 45;77 Capsid 78 84 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Interestingly, replication of WT and V86M NL4-3 in shRNA-CypA/R332G TRIM5alphahu-expressing cells was highly increased compared with replication in the shRNA-Luc cells. 2013 Retrovirology Result HIV R332G;V86M 62;37 67;41 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Like before, CsA decreased replication of both WT and V86M HIV-1NL-GFP in the permissive control "vector" cells by 30% to 50% in both TE671 cells (Figure 3A) and Sup-T1 cells (Figure 3B). 2013 Retrovirology Result HIV V86M 54 58 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Likewise, CsA treatment strongly increased replication of WT HIV-1NL-GFP in R332G-R335G TRIM5alphahu cells (about 10-times in TE671, 5-times in Sup-T1 cells) but had a much smaller effect on V86M HIV-1NL-GFP (1.5- to 2-fold in both cell lines). 2013 Retrovirology Result HIV R332G;R335G;V86M 76;82;191 81;87;195 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Next, we determined the catalysed isomerisation rate of the G89-P90 bond in both WT and V86M capsids in the presence of CypA (Figure 6B). 2013 Retrovirology Result HIV V86M 88 92 Capsid 93 100 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Non-transduced cells were eliminated by antibiotic treatment, and cells were then challenged with either WT or V86M NL4-3 vectors in the presence or absence of 2 muM CsA (Figure 2). 2013 Retrovirology Result HIV V86M 111 115 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. qPCR assays were performed on DNA extracted from TE671 cells expressing either WT TRIM5alphahu, R332G-R335G TRIM5alphahu or, as a positive control, TRIM5alpharh, and then infected with WT or V86M HIV-1NL-GFP (Figure 7). 2013 Retrovirology Result HIV R332G;R335G;V86M 96;102;191 101;107;195 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Replication of either WT or V86M NL4-3 was not detectable in the shRNA-Luc cells also expressing R332G-R335G TRIM5alphahu (Figure 8, top panel). 2013 Retrovirology Result HIV R332G;R335G;V86M 97;103;28 102;108;32 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Replication of HIV-1NL-GFP in these cells was enhanced either by introducing the V86M mutation (Additional file 1: Figure S3A) or by CsA treatment (Additional file 1: Figure S3B). 2013 Retrovirology Result HIV V86M 81 85 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Replication of V86M NL4-3 was no more efficient than that of its WT counterpart in these cells. 2013 Retrovirology Result HIV V86M 15 19 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Replication of V86M NL4-3 was not detected in the same cells, which suggests that V86M does not provide protection against this particular mutant of TRIM5alphahu in a spreading infection assay. 2013 Retrovirology Result HIV V86M;V86M 15;82 19;86 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Replication of WT NL4-3 in the control (vector) shRNA-Luc cells peaked at about 18 days post-infection, while replication of the V86M mutant in the same cells peaked at about 15 days. 2013 Retrovirology Result HIV V86M 129 133 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Restriction of V86M CA HIV-1 by R332G-R335G TRIM5alphahu in cat cells is insensitive to CsA. 2013 Retrovirology Result HIV R332G;R335G;V86M 32;38;15 37;43;19 Capsid 20 22 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Restriction of V86M CA HIV-1 by R332G-R335G TRIM5alphahu is independent of cyclophilin A. 2013 Retrovirology Result HIV R332G;R335G;V86M 32;38;15 37;43;19 Capsid 20 22 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The amounts of viral DNAs were more decreased in TRIM5alpharh cells than in R332G-R335G TRIM5alphahu cells, consistent with the greater magnitude of restriction conferred by TRIM5alpharh. 2013 Retrovirology Result HIV R332G;R335G 76;82 81;87 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The cell lines included in the experiment expressed R332G or R332G-R335G TRIM5alphahu and were co-transduced with the shRNA against CypA or the control shRNA targeting luciferase. 2013 Retrovirology Result HIV R332G;R332G;R335G 52;61;67 57;66;72 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The presence of an additional G89cis peak in V86M in the absence of CypA suggests that the mutant capsid may also undergo faster uncatalysed isomerisation, however we were not able to quantify this under the conditions tested. 2013 Retrovirology Result HIV V86M 45 49 Capsid 98 104 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The sensitivity of HIV-1 restriction by TRIM5alphahu mutants to the V86M mutation correlates with its sensitivity to CsA treatment. 2013 Retrovirology Result HIV V86M 68 72 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The V86M mutation in CA prevented the use of a sensitive CAp24 assay to monitor replication. 2013 Retrovirology Result HIV V86M 4 8 Capsid;Capsid 21;57 23;59 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Therefore, if the V86M mutation conferred some level of resistance to R332G-R335G TRIM5alphahu in a spreading infection context, it did not do so at levels high enough to allow detection of replication. 2013 Retrovirology Result HIV R332G;R335G;V86M 70;76;18 75;81;22 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Therefore, replication of V86M CA HIV-1 in cells expressing R332G-R335G TRIM5alphahu was not efficiently rescued by depletion or inhibition of CypA. 2013 Retrovirology Result HIV R332G;R335G;V86M 60;66;26 65;71;30 Capsid 31 33 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. This analysis supports our findings that V86M and CsA treatment rescue HIV-1 replication in restrictive conditions by redundant mechanisms. 2013 Retrovirology Result HIV V86M 41 45 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. This suggests that CypA knockdown can rescue replication of these two viruses in TRIM5-restrictive conditions and also that V86M NL4-3 is more sensitive to restriction by R332G TRIM5alphahu, in contradiction with the data obtained in vector transduction experiments. 2013 Retrovirology Result HIV R332G;V86M 171;124 176;128 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. This suggests that the V86M mutation has both altered the conformations adopted by the CypA-binding loop and increased the rate at which it is isomerised. 2013 Retrovirology Result HIV V86M 23 27 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. This supports the hypothesis that the V86M mutation results in distinct populations of conformers for the G89-P90 bond. 2013 Retrovirology Result HIV V86M 38 42 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. This was more obvious for the V86M virus which peaked at about 18 days, confirming that CA-V86M HIV-1 depends on CypA for optimal replication in human cells. 2013 Retrovirology Result HIV V86M;V86M 30;91 34;95 Capsid 88 90 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Thus, V86M did not affect the fitness of HIV-1 in Sup-T1 cells. 2013 Retrovirology Result HIV V86M 6 10 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Thus, we hypothesized that V86M could modify the interactions between HIV-1 CA and CypA, or the isomerisation of the former by the latter. 2013 Retrovirology Result HIV V86M 27 31 Capsid 76 78 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. To address these issues, we analyzed the rescue of HIV-1 replication by V86M mutation and/or by CsA treatment under restriction by R332G-R335G TRIM5alphahu in CRFK cat fibroblasts. 2013 Retrovirology Result HIV R332G;R335G;V86M 131;137;72 136;142;76 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. To directly analyze the role of CypA in V86M-mediated resistance, we knocked down its expression in TE671 and in Sup-T1 cells that had been transduced with WT or R332G-R335G TRIM5alphahu or with the empty vector. 2013 Retrovirology Result HIV R332G;R335G;V86M 162;168;40 167;173;44 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Upon addition of CypA, symmetrical exchange peaks were observed for WT and V86M indicating that both capsids are a substrate for CypA and that increased cis-trans exchange occurs during the ZZ-exchange experiment. 2013 Retrovirology Result HIV V86M 75 79 Capsid 101 108 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M CA interactions with CypA studied by NMR. 2013 Retrovirology Result HIV V86M 0 4 Capsid 5 7 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M had no effect on total DNA levels but significantly increased relative amounts of 2-LTR nuclear DNA species. 2013 Retrovirology Result HIV V86M 0 4 LTR 89 92 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M NL4-3 peaked at about 35 days post-infection in the shRNA-CypA/R332G TRIM5alphahu-expressing cells while its replication was not detected in the shRNA-Luc/R332G cells. 2013 Retrovirology Result HIV R332G;R332G;V86M 68;160;0 73;165;4 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. We analyzed whether V86M could protect HIV-1 against restriction by TRIM5alphahu mutant R332G-R335G in human TE671, human Sup-T1 and feline CRFK cells. 2013 Retrovirology Result HIV R332G;R335G;V86M 88;94;20 93;99;24 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. We found that R332G-R335G TRIM5alphahu strongly restricted HIV-1NL-GFP, and the mutation V86M in CA decreased restriction by about 3-fold (Figure 5). 2013 Retrovirology Result HIV R332G;R335G;V86M 14;20;89 19;25;93 Capsid 97 99 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. When we plotted the increase in HIV-1NL-GFP infectivity resulting from V86M against the increase in infectivity resulting from CsA treatment in TE671 expressing these various TRIM5alphahu, we observed a highly significant correlation (Figure 4). 2013 Retrovirology Result HIV V86M 71 75 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. WT HIV-1NL-GFP replication was enhanced 10-times by CsA treatment while the effect of the drug on the replication of V86M HIV-1NL-GFP was much smaller (1.5-fold), thus mirroring the data obtained in human cells. 2013 Retrovirology Result HIV V86M 117 121 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Among the 78 treatment-failing patients seven (9.1%) carried major PI-related mutations (Table 6), nine (11.5%) had thymidine-analog mutations (TAMs), 29 (37.2%) other NRTI-related mutations (of those, 27 (35%) had M184V, the most prevalent mutation), and 32 (41.0%) had NNRTI-related mutations (Table 5). 2013 PloS one Result HIV M184V 215 220 NNRTI;NRTI;PI 271;168;67 276;172;69 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Interestingly, cluster 3 included four drug-naive patients infected with K103N-containing virus (Figure 2, red circles), two of whom also had syphilis, and the MSMs in cluster 1 included two sero-convertors. 2013 PloS one Result HIV K103N 73 78 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. The latter differed significantly in the frequencies of the major resistance RT mutations T215FY and K219QE (NRTI) and of several secondary/accessory mutations, including: the protease mutations I13V, M36I, I62V, L63P, A71V, V77I, L89M and I93L (Table 6) and the RT mutations A98S, K101N, K103R and V179I (Table 5). 2013 PloS one Result HIV A71V;A98S;I13V;I62V;I93L;K101N;K103R;K219E;K219Q;L63P;L89M;M36I;T215F;T215Y;V179I;V77I 219;276;195;207;240;282;289;101;101;213;231;201;90;90;299;225 223;280;199;211;244;287;294;107;107;217;235;205;96;96;304;229 PR;NRTI;RT;RT 176;109;77;263 184;113;79;265 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. The most frequent mutation was K103N, in 7 individuals. 2013 PloS one Result HIV K103N 31 36 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Thirty-four drug-naive patients (14.5%) carried the RT mutation A62V. 2013 PloS one Result HIV A62V 64 68 RT 52 54 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Twenty-three, including 21 for whom these drugs where part of their first-line therapy, had at least one major NNRTI mutation, with K103N and G190A/S being the most prevalent (Table 5). 2013 PloS one Result HIV G190A;G190S;K103N 142;142;132 149;149;137 NNRTI 111 116 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Two carried the protease mutation M46I; three had NRTI-related mutations; 11 non-nucleoside reverse transcriptase inhibitors (NNRTI); and one was resistant to NRTI and NNRTI. 2013 PloS one Result HIV M46I 34 38 NNRTI;PR;NNRTI;NNRTI;NRTI;NRTI 77;16;126;168;50;159 113;24;131;173;54;163 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. A reduction in KR21 affinity for S375A, combined with the unaltered affinity of the mutant for sCD4, leads one to speculate that the latter would be more resistant to KR21 inhibition of gp120/sCD4 interaction. 2013 Biochemistry Result HIV S375A 33 38 gp120 186 191 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Consistent with the direct binding data, the competition results show a large-scale reduction (20 fold) in the sCD4/S375A inhibitory potency of KR21 compared to WT gp120. 2013 Biochemistry Result HIV S375A 116 121 gp120 164 169 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Fitting of the results to a 4-parameter logistic curve yielded IC50 values of 65 nM and 1283 nM for WT and S375A, respectively. 2013 Biochemistry Result HIV S375A 107 112 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Fitting of the sensorgram data to a steady state 1:1 affinity model (Materials and Methods) yielded KD = 37 nM for WT and KD = 41 nM for S375A gp120. 2013 Biochemistry Result HIV S375A 137 142 gp120 143 148 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Hence, S375A maintains correct gp120 folding and activity. 2013 Biochemistry Result HIV S375A 7 12 gp120 31 36 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Measuring the inhibitory potency of KR21 for PT/gp120 interaction provides an alternative means to quantify the effect of S375A mutation on PT/gp120 interaction. 2013 Biochemistry Result HIV S375A 122 127 gp120;gp120 48;143 53;148 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. More specifically, we took into account the effect that the S375W and I423P mutations have on 12p1 inhibition of gp120 interactions with different ligands, along with information on the conformation targeted by the peptide gleaned from antibody binding data and isothermal titration calorimetry. 2013 Biochemistry Result HIV I423P;S375W 70;60 75;65 gp120 113 118 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Previous work has shown that the parent peptide 12p1 does not inhibit binding of sCD4 to a mutant gp120 (S375W) that has a propensity to sample the activated/CD4-bound state , while it inhibits binding of the F105 antibody to a mutant gp120 (I423P) which is inefficient at assuming the activated state . 2013 Biochemistry Result HIV I423P;S375W 243;105 248;110 gp120;gp120 98;236 103;241 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Previously, it was reported that a pocket-filling S375W mutation in gp120 completely abrogated binding of the parent 12p1 peptide . 2013 Biochemistry Result HIV S375W 50 55 gp120 68 73 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Steady state fits for WT sensograms yielded KD = 9 nM for KR21/gp120 interactions, but KR21 binding to S375A was severely disrupted and we could not fit the data. 2013 Biochemistry Result HIV S375A 103 108 gp120 63 68 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. We first verified the functionality of the S375A gp120 mutant by measuring its affinity for sCD4 (Figure 11). 2013 Biochemistry Result HIV S375A 43 48 gp120 49 54 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. We then probed the affinity of KR21 for this mutant by a direct binding SPR assay wherein serial dilutions of the peptide were injected over immobilized WT and S375A (Figure 12). 2013 Biochemistry Result HIV S375A 160 165 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. In addition, altering any of the three polymorphic amino acids (A37V, N172D, and R193Q) back to the UA159 sequence and transforming the double mutant folP gene into the E. 2013 International journal of microbiology Result HIV A37V;N172D;R193Q 64;70;81 68;75;86 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. In the present paper, the above-mentioned four point mutations (A46V, E80K, Q122H, and S146G), and those in S. 2013 International journal of microbiology Result HIV A46V;E80K;Q122H;S146G 64;70;76;87 68;74;81;92 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. Moreover, changing the DNA encoding four amino acid mutations (A46V, E80K, Q122H, and S146G) of folP in S. 2013 International journal of microbiology Result HIV A46V;E80K;Q122H;S146G 63;69;75;86 67;73;80;91 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. mutans isolate 797 carries four point mutations (A46V, E80K, Q122H, and S146G) in folP gene, as compared to the control strain NN2025 but harbours one such mutation (S146G) if compared to control strain UA159 (Table 1). 2013 International journal of microbiology Result HIV A46V;E80K;Q122H;S146G;S146G 49;55;61;72;166 53;59;66;77;171 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. mutans isolate 8 (A37V, N172D, and R193Q) (Table 1), were successfully altered or removed from folP gene by site-directed mutagenesis. 2013 International journal of microbiology Result HIV A37V;N172D;R193Q 18;24;35 22;29;40 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. mutans isolate 8 (bearing the mutations A37V, N172D, and R193Q) conferred (to folP knockout E. 2013 International journal of microbiology Result HIV A37V;N172D;R193Q 40;46;57 44;51;62 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. These were isolate 8 (A37V, N172D, and R193Q) and isolate 135 (A63S, W174L, L175F, and M189I). 2013 International journal of microbiology Result HIV A37V;A63S;L175F;M189I;N172D;R193Q;W174L 22;63;76;87;28;39;69 26;67;81;92;33;44;74 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. A subset of CM243 gp140 mutants which expressed protein at levels comparable to wild-type CM243 gp140 (N610Q, N615Q, N610/615Q and N610/615/624/636Q) . 2013 PloS one Result HIV N610Q;N615Q 103;110 108;115 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Among those mAbs that bind to oligomer-specific epitopes in Cluster I (mAbs T4, T6, T9, and T10), the binding of each to the quadruple mutant, gp140CM243(N610/615/624/636Q), was reduced, while there was some indication that mAbs T4 and T10 reacted slightly better to CM243 mutants N601Q, N615Q and N610/615Q. 2013 PloS one Result HIV N601Q;N615Q 281;288 286;293 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Neutralization >=50% at a 1:5 dilution was observed for at least one monkey serum in the R2 immunization group against 14 of the 18 virus strains tested, in the 14/00/4 group against 10/18 strains, in the CM243(N610Q) group against 7/18 strains, and in the trivalent group against 11/18 strains. 2013 PloS one Result HIV N610Q 211 216 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Only two sera from the R2 group and one from the 14/00/4 group neutralized CM243(N610Q) virus at dilutions of 1:20. 2013 PloS one Result HIV N610Q 81 86 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The CM243 gp140 wild-type and mutants N615Q and N610Q were capable of some processing of the gp140 glycoprotein into the gp120 and gp41 ectodomain in comparison to HIV-1 IIIB gp140, and a shift in the mobility of the gp41 ectodomain in mutants N615Q and N610Q reveals their loss of N-linked glycosylation at those sites . 2013 PloS one Result HIV N610Q;N610Q;N615Q;N615Q 48;254;38;244 53;259;43;249 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The homologous neutralization results confirmed the somewhat greater breadth of response induced by R2 Env as compared to the 14/00/4 Env and the poorer responses induced by CM243(N610Q) Env; indeed, the CM243(N610Q) virus was generally resistant to neutralization by monkey sera. 2013 PloS one Result HIV N610Q;N610Q 180;210 185;215 Env;Env;Env 103;134;187 106;137;190 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The number of serum-virus combinations associated with neutralization for all sera per group against all viruses differed significantly in comparisons of the R2 group to the 14/00/4 and CM243(N610Q) groups, the 14/00/4 group to the CM243(N610Q) group, and the CM243(N610Q) group to the Trivalent group. 2013 PloS one Result HIV N610Q;N610Q;N610Q 192;238;266 197;243;271 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The numbers of serum-virus combinations associated with neutralization >=50% were 37, 24, 11, and 35 of 108 total per group for the R2, 14/00/4, CM243(N610Q), and trivalent immunogen groups, respectively. 2013 PloS one Result HIV N610Q 151 156 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The sera from the rabbits immunized with CM243(N610Q) gp140 also neutralized the HIV-1 strains R2, SF162, and 14/00/4 (all Tier 1 strains), while the control sera and sera from rabbits immunized with CM243 gp140 did not (not shown). 2013 PloS one Result HIV N610Q 47 52 gp140;gp140 54;206 59;211 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Thus, the data indicated that the R2 and trivalent immunogens induced similar responses, R2 was slightly more effective at inducing neutralizing antibodies than 14/00/4, and CM243(N610Q) was least immunogenic. 2013 PloS one Result HIV N610Q 180 185 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. When these mutations were analyzed in the context of full length Env, all mutants were significantly impaired in their ability to mediate cell-cell fusion except CM243(N610Q) which exhibited fusion activity at a level approximately 50% of wild-type CM243 Env . 2013 PloS one Result HIV N610Q 168 173 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Also, Cycloheximide (CHX) chase assay was performed to study the effect of S61A mutation (Figure 2C) on the intracellular turnover and kinetic stability of Vpu protein. 2013 PloS one Result HIV S61A 75 79 Vpu 156 159 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. HEK-293T cells were transfected with mammalian expression vectors encoding S61A mutants and wild type (wt) Vpu variant. 2013 PloS one Result HIV S61A 75 79 Vpu 107 110 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. However, one S61A variant allele, Vpu 7, containing a transmembrane deletion of eight amino acids (Figure 3C, panel 8), when compared with other S61A alleles, showed moderate enhancement of viral release (Figure 3A, panel 8 and Figure 3C). 2013 PloS one Result HIV S61A;S61A 13;145 17;149 Vpu 34 37 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Immunoblotting performed with equivalent amounts of lysates from infected cells (Figure 4B) also confirmed higher expression levels associated with group B S61A variants (Figure 4B, lanes 7, 8 and 9) as compared to S61+ variants (Figure 4B, lanes 4, 5 and 6). 2013 PloS one Result HIV S61A 156 160 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. In contrast, a comparative analysis of two Vpu alleles (with or without S61A mutation) revealed that S61A mutant allele (Figure 2C, panel 3) showed almost no reduction in protein levels when compared with S61 variants (Figure 2C, panel 4) which was comparable to wt subtype B and C Vpu protein (Figure 2C, panels 1 and 2). 2013 PloS one Result HIV S61A;S61A 72;101 76;105 Vpu;Vpu 43;282 46;285 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Interestingly, all the three S61A variants tested (Vpu 1, 7 and S2) showed marked inhibition of Vpu-specific ubiquitination (Figure 2D, Lanes 7, 8 and 9) as compared to S61 wt alleles (Figure 2D, Lanes 4, 5 and 6). 2013 PloS one Result HIV S61A 29 33 Vpu;Vpu 51;96 54;99 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Notably, S61A variants (Figure 2A, Lanes 4 and 5) showed higher expression levels than S61 wt Vpu alleles (Figure 2A, Lanes 2 and 3). 2013 PloS one Result HIV S61A 9 13 Vpu 94 97 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Site directed mutagenesis studies with S61A substitution in Vpu B was earlier reported to confer higher intracellular stability that correlated with enhanced rate of virus replication. 2013 PloS one Result HIV S61A 39 43 Vpu 60 63 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. The S61A Mutation Conferred Enhanced Intracellular Stability. 2013 PloS one Result HIV S61A 4 8 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. These results clearly show that acquisition of S61A mutation inhibits Vpu ubiquitination conferring increased intracellular stability and responsible for relative protein abundance. 2013 PloS one Result HIV S61A 47 51 Vpu 70 73 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Two of the natural S61A variants were most potent in their ability to cause virus release (Figure 3A, panels 5, 6 and quantitation showed in Figure 3C). 2013 PloS one Result HIV S61A 19 23 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. We also report positive selection among group B Vpu variants that possessed a unique S61A substitution. 2013 PloS one Result HIV S61A 85 89 Vpu 48 51 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. We first wanted to test the functional implication of natural S61A substitution and other variations with respect to intracellular stability. 2013 PloS one Result HIV S61A 62 66 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. When analyzed for their relative potential to induce cell death, group B S61A variants (Figure 4A, panels 5, 6 and 7) caused cell death as comparable to wt subtype B Vpu (Figure 4A, panel 3). 2013 PloS one Result HIV S61A 73 77 Vpu 166 169 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. An example of the Gaussian reconstruction of the distance profile for M36I/A71V is shown in Figure 3A. 2013 Biochemistry Result HIV A71V;M36I 75;70 79;74 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Distance profiles between the two spin probes incorporated into the flaps at site K55C/K55C' were determined from DEER spectroscopy (also referred to as PELDOR). 2013 Biochemistry Result HIV K55C 87 91 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. For A71V, D30N/M36I, D30N/A71V, and M36I/A71V the most probable distance occurs at a shorter distance of ~ 33 A (solid line); which is a distance consistent with a closed-like or closed conformation. 2013 Biochemistry Result HIV A71V;A71V;A71V;D30N;D30N;M36I;M36I 4;26;41;10;21;15;36 8;30;45;14;25;19;40 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. For A71V, D30N/M36I, M36I/A71V and D30N/M36I/A71V, a small but distinct peak in the distance range of 40-45 A is observed. 2013 Biochemistry Result HIV A71V;D30N;M36I;A71V;A71V;D30N;M36I;M36I 45;35;40;4;26;10;15;21 49;39;44;8;30;14;19;25 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. For the other constructs investigated, the slope of the initial echo decay is similar to WT, signifying most probable distances consistent with a predominant semi-open conformation or comparable closed and semi-open populations (e.g., D30N/M36I) as seen for other apo HIV-1 PR constructs. 2013 Biochemistry Result HIV D30N;M36I 235;240 239;244 PR 274 276 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. For the triple mutation construct, D30N/M36I/A71V, upon addition of CA-p2, a shift of the most probable distance occurred from 35 A to 33 A, similar to those observed for D30N and M36I constructs bound to CA-p2. 2013 Biochemistry Result HIV A71V;D30N;M36I;D30N;M36I 45;35;40;171;180 49;39;44;175;184 Capsid;Capsid 68;205 70;207 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. For WT, D30N, M36I and D30N/M36I/A71V, the most-probable inter-spin distance occurs near 35-37 A (dashed line), corresponding to occupancy of the semi-open conformation. 2013 Biochemistry Result HIV A71V;D30N;M36I;D30N;M36I 33;23;28;8;14 37;27;32;12;18 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. However, in this case, addition of RTV did not induce flap closure in D30N/M36I/A71V (Figure 4D) and the most probable distance was seen to remain at 35 A. 2013 Biochemistry Result HIV A71V;D30N;M36I 80;70;75 84;74;79 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. In contrast, the most probable distance for the A71V DEER distance profile (Figure 4C) remains unchanged at 33 A upon addition of substrate mimic or inhibitor, suggesting that the most probable distance of 33 A for the apoenzyme is consistent with a high occupancy of a closed-like conformer in the absence of a ligand. 2013 Biochemistry Result HIV A71V 48 52 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Noticeably, the distance distribution widths are narrower for A71V in the presence of substrate mimic or inhibitor, with a 33% and 27% increase in the percentage occupancy of the closed state for CA-p2 and RTV, respectively. 2013 Biochemistry Result HIV A71V 62 66 Capsid 196 198 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The area-normalized distance profiles in the presence of the non-hydrolyzable substrate mimic (CA-p2) and ritonavir (RTV) overlaid with the apoenzyme (apo) reveal a shift of the most probable distance from 35-37 A to 33 A in D30N and M36I constructs (Figures 4A and B), indicating a conformational shift in favor of the closed state. 2013 Biochemistry Result HIV D30N;M36I 225;234 229;238 Capsid 95 97 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The bar graphs in the figure insets show 60% and 66% increase of the closed population percentage for CA-p2 or RTV-bound D30N and M36I, respectively. 2013 Biochemistry Result HIV D30N;M36I 121;130 125;134 Capsid 102 104 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The effects that accumulated primary and secondary mutations have on flap conformational sampling were determined from a series of single, double and triple mutant constructs containing amino acid substitutions D30N, M36I and A71V (all sequence details given in Supporting Information). 2013 Biochemistry Result HIV A71V;D30N;M36I 226;211;217 230;215;221 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The secondary mutation, A71V alone or in combination with either D30N or M36I (i.e., A71V, D30N/A71V, and M36I/A71V), results in a steeper echo decay at tau < 0.50 mus (solid line), indicating that shorter distances consistent with a closed conformation, as seen previously upon inhibitor binding, dominate in the corresponding distance profiles. 2013 Biochemistry Result HIV A71V;A71V;A71V;A71V;D30N;D30N;M36I;M36I 24;85;96;111;65;91;73;106 28;89;100;115;69;95;77;110 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. To monitor the effect of inhibitor-binding to the flap conformational sampling of HIV-1 PR containing single point mutations, four-fold molar excess of inhibitor or substrate mimic was added to MTSL-labeled D30N, M36I, A71V and D30N/M36I/A71V subtype B HIV-1 PR constructs. 2013 Biochemistry Result HIV A71V;D30N;M36I;A71V;D30N;M36I 238;228;233;219;207;213 242;232;237;223;211;217 PR;PR 88;259 90;261 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). K103N was the most frequently detected mutation, present in 19/26 samples having drug resistance (73%). 2013 PloS one Result HIV K103N 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). The following mutations were detected in only one sample each: M46L and I85V (protease); K65R, L74I, K219E/R, and K101E (reverse transcriptase) (Figure 4). 2013 PloS one Result HIV I85V;K101E;K219E;K219R;K65R;L74I;M46L 72;114;101;101;89;95;63 76;119;108;108;93;99;67 RT;PR 121;78 142;86 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). There were also multiple occurrences of V106M (n = 4), M184V (n = 4), Y181C (n = 2) and G190A (n = 2). 2013 PloS one Result HIV G190A;M184V;V106M;Y181C 88;55;40;70 93;60;45;75 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Also, the PR20 structure does not show the dynamic side chain positions of Asn30 observed in various D30N single and double mutants like D30N/N88D and D30N/N88S. 2013 Journal of medicinal chemistry Result HIV D30N;D30N;D30N;N88D;N88S 101;137;151;142;156 105;141;155;146;160 PR 10 12 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Comparison with the PR/amprenavir structure reveals that mutations D30N, V32I, I47V and I84V in PR20 alter the size, shape and charge of the S2/S2' pocket in the PR20/amprenavir complex as described previously for the PR20/darunavir and PR20/saquinavir (3UFN) complexes. 2013 Journal of medicinal chemistry Result HIV D30N;I47V;I84V;V32I 67;79;88;73 71;83;92;77 PR;PR;PR;PR;PR 20;96;162;218;237 22;98;164;220;239 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. For example, the L10F mediated breakage of inter-monomer ion pair between Arg8-Asp29' and Arg8'-Asp29 is observed in all three complexes with the exception of a minor conformation of Arg8 in PR20/2 retaining an ion pair with Asp29'. 2013 Journal of medicinal chemistry Result HIV L10F 17 21 Asp;Asp;Asp;PR 79;96;225;191 82;99;228;193 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. However, the P1'-pyrrolidinone in PR20 does not form the water-molecule mediated hydrogen bond with the side chain of Arg8 presumably due to the L10F mutation (Figure 5B). 2013 Journal of medicinal chemistry Result HIV L10F 145 149 PR 34 36 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. In addition, the smaller I84V mutation results in the loss of the van der Waals contact seen between the sulfonyl oxygen of amprenavir and Ile 84' of wild-type PR. 2013 Journal of medicinal chemistry Result HIV I84V 25 29 PR 160 162 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. In contrast, the THF ring in the PR20 complex is shifted towards the I47V mutation in comparison with the position in the wild-type PR complex (Figure 4C). 2013 Journal of medicinal chemistry Result HIV I47V 69 73 PR;PR 33;132 35;134 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Studies of PR with single mutations, however, suggested 3 would be less effective on variants with the I50V mutation. 2013 Journal of medicinal chemistry Result HIV I50V 103 107 PR 11 13 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. The increase in size and the loss of charge in the S2 pocket of PR20 causes the THF ring of amprenavir to shift towards I84V resulting in an elongated C-H...O interaction (from 3.3 to 3.6 A) with the flap residue Gly48 compared to the wild-type PR. 2013 Journal of medicinal chemistry Result HIV I84V 120 124 PR;PR 64;245 66;247 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. The L10F mutation facilitates flipping of the Arg8 side chain to form van der Waals contacts with the bulky Phe10 side chain, which breaks the intersubunit ion pair between Arg8 and Asp29'. 2013 Journal of medicinal chemistry Result HIV L10F 4 8 Asp 182 185 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. The second conformation of P1'-pyrrolidinone is likely not favored in the PR20/2 structure due to the I54L mutation, which displaces Pro81' by ~1.6 A eliminating its potential interactions with the second P1' conformation found in the wild type PR complex (Figure 5C). 2013 Journal of medicinal chemistry Result HIV I54L 102 106 PR;PR 74;245 76;247 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. The shorter side chain of I47V mutation in the PR20/amprenavir complex removes interactions of the side chain with the P2 THF ring of amprenavir (Figure 4C) but its contact with the P2' aniline group is retained. 2013 Journal of medicinal chemistry Result HIV I47V 26 30 PR 47 49 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. The wild type enzymes from HIV-1 and HIV-2 share 39-48% sequence identity; however, several of the mutations in PR20 exist in the wild type PR2 sequence including V32I and I47V in the S2/S2' subsites. 2013 Journal of medicinal chemistry Result HIV I47V;V32I 172;163 176;167 PR;PR 140;112 143;114 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Thus, changes due to PR20 mutations L10F and I54L may correlate with the higher KL value for inhibitor 2 relative to the related PIs lacking the P1'-pyrrolidinone. 2013 Journal of medicinal chemistry Result HIV I54L;L10F 45;36 49;40 PI;PR 129;21 132;23 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Thus, mutation N88D may compensate for the change due to D30N mutation in the active site cavity of PR20. 2013 Journal of medicinal chemistry Result HIV D30N;N88D 57;15 61;19 PR 100 102 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. Both isolates presented the M46L mutation-conferring intermediate-level resistance to nelfinavir and potential low-level resistance to lopinavir and atazanavir-alone in the subtype C strain and along with multiple other resistance mutations, such as L24I, I47V, F53L, I54V, and V82A in the F1 strain. 2013 Journal of medical virology Result HIV F53L;I47V;I54V;L24I;M46L;V82A 262;256;268;250;28;278 266;260;272;254;32;282 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. M184V, the 3TC-selected mutation was identified in three HIV resistant strains, alone in two cases and together with all the above mentioned type II TAMs, as well as other NRTI conferring resistance mutations (T69D and L74I) in one case. 2013 Journal of medical virology Result HIV L74I;T69D;M184V 219;210;0 223;215;5 NRTI 172 176 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. Several atypical substitutions at key positions known to be linked with drug resistance were detected also within the RT gene: for NRTI-T69S (1/61 patients), T69N (2/61 patients) and for NNRTI-E138A/ G (5/61 patients), H221Y (1/61 patients). 2013 Journal of medical virology Result HIV E138A;H221Y;T69N;T69S 193;219;158;136 198;224;162;140 NNRTI;NRTI;RT 187;131;118 192;135;120 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. TDR associated with NNRTIs (Table II) was identified only in 2 HIV-1-subtype F1 strains (2/9): one isolate carried V179F and Y181C mutations, and the other one harbored mutations Y188C and Y106M, all conferring resistance across the entire NNRTIs class. 2013 Journal of medical virology Result HIV V179F;Y106M;Y181C;Y188C 115;189;125;179 120;194;130;184 NNRTI;NNRTI 20;240 26;246 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The analysis of the RT gene also revealed many accessory mutations presented in all studied sequences, encountered most frequently at positions V35T, T39A, V60I, I135L, A272P, I293V. 2013 Journal of medical virology Result HIV A272P;I135L;I293V;T39A;V35T;V60I 169;162;176;150;144;156 174;167;181;154;148;160 RT 20 22 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The most common accessory PI resistance mutations found were M36I (56/61 patients) and R41K (56/61 patients), followed by mutations L89M (51/61), I15V (50/61), and L63T (41/61). 2013 Journal of medical virology Result HIV I15V;L63T;L89M;M36I;R41K 146;164;132;61;87 150;168;136;65;91 PI 26 28 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The Q151M multinucleoside resistance complex, which causes high or intermediate-level resistance to all NRTIs was not present. 2013 Journal of medical virology Result HIV Q151M 4 9 NRTI 104 109 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The type I TAMs (M41L and L210W) were observed each in only 1 case. 2013 Journal of medical virology Result HIV L210W;M41L 26;17 31;22 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. Thymidine analogues mutations (TAMs), selected mostly by ZDV and d4T, were prevalent (6/9; 66.66%), with type II TAMs being more frequently detected (4/9; 44.44%): K70R and K219Q (each in three cases), D67N and T215F (each in two cases). 2013 Journal of medical virology Result HIV D67N;K219Q;K70R;T215F 202;173;164;211 206;178;168;216 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. 3C indicate that K601D and K601N DSR mutations promote shedding of gp120 into culture supernatants of transfected cells by ~6.8- and 4.4-fold with respect to WT, respectively, while cell-cell fusion activity was reduced by ~85-90% . 2013 PLoS pathogens Result HIV K601D;K601N 18;28 23;33 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. 3D ), suggesting that loss of the Asn142 glycan can substitute for the N139INN deletion. 2013 PLoS pathogens Result HIV N139I;N139N 71;71 78;78 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. 5D indicate that the T138N/L494I/K601N, DeltaN139INN/K601N and WT Envs exhibited almost identical patterns of mutant CCR5 utilization. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N 34;28;22;54 39;33;27;59 Env 67 71 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. 7 ) show step-wise ~0.5log10-increases in the neutralization sensitivities of T138N and DeltaN139INN to the monoclonal NAb 2G12, which is directed to a glycan cluster involving Asn295, Asn332 Asn339, Asn386 and Asn392 on the outer face of gp120). 2013 PLoS pathogens Result HIV T138N 78 83 gp120 239 244 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. A single clone (P0.D50.10) contained S144N, which ablates the nearby PNGS at N142SS. 2013 PLoS pathogens Result HIV N142S;S144N 77;37 83;42 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. As was observed in the cell-cell fusion assay, the DeltaN139INN/K601N virus inhibition curve was shifted to the left, with an IC50 of ~1.3 microg/ml, confirming that DeltaN139INN/K601N is more resistant to the CD4-based inhibitor relative to WT and T138N/L494I/K601N in a virion context. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N;K601N 261;255;249;64;179 266;260;254;69;184 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. By contrast, improvements in gp120-gp41 association did not follow the combination of K601N with S143N, S158N, N160Q or S188N, consistent with their lack of fusion activity. 2013 PLoS pathogens Result HIV K601N;N160Q;S143N;S158N;S188N 86;111;97;104;120 91;116;102;109;125 gp120;gp41 29;35 34;39 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. By contrast, W596L exhibited WT fusion levels in combination with T138N. 2013 PLoS pathogens Result HIV T138N;W596L 66;13 71;18 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. By day 50, when mutant viral replication approached that of WT, the T138N/L494I/K601N triple mutation was present in 42% of clones. 2013 PLoS pathogens Result HIV K601N;L494I;T138N 80;74;68 85;79;73 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Cell-to-cell fusion function was blocked by K601D at sub-saturating Env conditions . 2013 PLoS pathogens Result HIV K601D 44 49 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Combining S144N (a PNGS mutation observed in clone P0.D50.10) with K601N resulted in almost identical fusion activity to DeltaN139INN/K601N . 2013 PLoS pathogens Result HIV K601N;K601N;S144N 67;134;10 72;139;15 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Complete inhibition of virus infectivity was achieved with 15 microg/ml of CD4-IgG2 with WT and T138N/L494I/K601N exhibiting similar sensitivities to the fusion protein (IC50~0.3 microg/ml) . 2013 PLoS pathogens Result HIV K601N;L494I;T138N 108;102;96 113;107;101 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Consistent with this finding, K601D-mutated HIV-1AD8 virus particles were largely devoid of gp120 . 2013 PLoS pathogens Result HIV K601D 30 35 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Deletion of residues N139INN (DeltaN139INN) from V1, that results in the loss of overlapping PNGSs at positions 141 and 142 (N141N142SS), was observed in 3/14 P2 day-30 clones, while 2/14 possessed mutations at Thr138; K601N was also observed in 50% of P2-day 30 clones . 2013 PLoS pathogens Result HIV K601N;N139I;N139N 219;21;21 224;28;28 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Even though, most of the V1V2 glycan mutants were fusogenic on a WT background, only T138N and S144N restored function to K601N. 2013 PLoS pathogens Result HIV K601N;S144N;T138N 122;95;85 127;100;90 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Figure 4B indicates that in a WT Env context, T138N and S188N did not affect cell-cell fusion, S143N, S144N and N160Q led to small but significant functional enhancements, whereas S158N blocked fusion completely. 2013 PLoS pathogens Result HIV N160Q;S143N;S144N;S158N;S188N;T138N;N160Q;S143N;S144N;S158N;S188N;T138N 114;97;104;182;58;48;113;96;103;181;57;47 119;102;109;187;63;53;118;101;108;186;62;52 Env 34 37 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Figure 5B indicates that WT and T138N/L494I/K601N have almost identical sensitivities to sCD4 with IC50s of ~60 microg/ml, which are comparable to previously published values for both T cell-line adapted and primary HIV-1 Envs. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N;L494I;T138N 46;40;34;45;39;33 51;45;39;50;44;38 Env 223 227 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Figure 5F indicates that T138N/L494I/K601N, DeltaN139INN/K601N and WT Envs exhibited almost identical C34 fusion inhibition curves with IC50s of ~100 nM. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N;K601N;L494I;T138N;K601N 39;33;27;59;38;32;26;58 44;38;32;64;43;37;31;63 Env 71 75 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Figures 3E and F indicate that T138N and DeltaN139INN do not increase the cell-cell fusion activity of surface expressed Env or the infectivity of Env-pseudotyped luciferase reporter virus when introduced to the WT background. 2013 PLoS pathogens Result HIV T138N;T138N 33;32 38;37 Env;Env 122;148 125;151 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Figures 6A and B indicate that T138N had no effect on cell-cell fusion when combined with L593V or K601D, whereas small improvements in glycoprotein association and fusion function were observed when L494I was added to the DSR mutants; wild type levels of gp120-gp41 association and fusion were attained when both T138N and L494I were combined with L593V or K601D. 2013 PLoS pathogens Result HIV K601D;K601D;L494I;L494I;L593V;L593V;T138N;T138N;K601D;K601D;L494I;L494I;L593V;L593V;T138N;T138N 102;361;203;327;93;352;34;317;100;359;201;325;91;350;32;315 107;366;208;332;98;357;39;322;105;364;206;330;96;355;37;320 gp120;gp41 257;263 262;267 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. For example, Q4A and Y14A (N-terminal domain, Nt), H88A (extracellular loop 1, ECL1), K171A, E172A and Q188A (extracellular loop 2, ECL2), and F264A and R274A (extracellular loop 3, ECL3) CCR5 mutants supported fusion with the 3 Env constructs to the same extent as WT CCR5, whereas fusion with Q280A (extracellular loop 3) was decreased to 25-40% of WT CCR5 activity. 2013 PLoS pathogens Result HIV E172A;F264A;H88A;K171A;Q188A;Q280A;Q4A;R274A 93;143;51;86;103;295;13;153 98;148;55;91;108;300;16;158 Env 229 232 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Genotypes of HIV-1AD8-K601D revertants. 2013 PLoS pathogens Result HIV K601D 22 27 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. However, the effect of K601N on Env function in the context of virus replication appears to be donor dependent (see . 2013 PLoS pathogens Result HIV K601N 23 28 Env 32 35 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Importantly, the presence of kifunensine did not affect the relative fusion activities of the T138N/L494I/K601N and DeltaN139INN/K601N revertant Envs with respect to wild type and K601D. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601D;K601N 106;100;94;180;129 111;105;99;185;134 Env 145 149 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. In order to identify suppressors of K601D, the env region was PCR-amplified from genomic DNA isolated from infected cells at days 20, 30, 40 and 50 for culture P0, and days 30 and 50 for culture P2. 2013 PLoS pathogens Result HIV K601D 36 41 Env 47 50 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. In this case, a reproducible ~2-fold increase in sensitivity to neutralization by HIVIG was observed with the V1 PNGS mutations (IC50~550 microg/ml for WT, 280 microg/ml for T138N and DeltaN139INN) indicating that these glycans are likely to modulate neutralization epitopes recognized by human immune sera. 2013 PLoS pathogens Result HIV T138N 174 179 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. In this study, we subjected the gp120-gp41 association defective DSR mutant HIV-1AD8-K601D to serial PBMC passage in order to select suppressor mutations. 2013 PLoS pathogens Result HIV K601D 85 90 gp120;gp41 32;38 37;42 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Interestingly, the L494I mutation was not observed in P2 clones. 2013 PLoS pathogens Result HIV L494I 19 24 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. It may be that lower receptor numbers and/or alternate coreceptor post-translational modifications on target cells, or differences in target cell population numbers in the case of the latter donor's PBMCs do not enable the fusion-activation threshold to be reached for K601N Env. 2013 PLoS pathogens Result HIV K601N 269 274 Env 275 278 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Near-WT levels of gp120-gp41 association were observed for the fusion-competent T138N/K601N mutant, whereas S144N/K601N, which is also fusion competent, exhibited a mild gp120 shedding phenotype. 2013 PLoS pathogens Result HIV K601N;K601N;S144N;T138N 86;114;108;80 91;119;113;85 gp120;gp120;gp41 18;170;24 23;175;28 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Phenotype and long-term culture of the HIV-1AD8-K601D DSR mutant. 2013 PLoS pathogens Result HIV K601D 48 53 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Pulse-chase biosynthetic labeling followed by radioimmunoprecipitation with pooled IgG derived from HIV-1-infected individuals (HIVIG) indicated WT-like gp120-gp41 association for T138N, S143N, S144N, N160Q and S188N and a shedding phenotype for the fusion-defective S158N . 2013 PLoS pathogens Result HIV N160Q;S143N;S144N;S158N;S188N;T138N 201;187;194;267;211;180 206;192;199;272;216;185 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Similar CD4 binding curves were observed for WT, T138N/L494I and DeltaN139INN gp120 mutants . 2013 PLoS pathogens Result HIV L494I;T138N 55;49 60;54 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. T138N-containing gp120 molecules migrated to lower molecular weight positions with respect to WT in reducing SDS-PAGE, consistent with loss of the glycan at Asn136 . 2013 PLoS pathogens Result HIV T138N 0 5 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The 2G12 IC50s for WT, T138N and DeltaN139INN were 13, 4 and 1.5 microg/ml, respectively. 2013 PLoS pathogens Result HIV T138N 23 28 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The abilities of T138N/L494I/K601N, DeltaN139INN/K601N and WT Envs to utilize a panel of CCR5 coreceptor mutants were next compared in order to determine if alterations to the mode of CCR5 engagement could account for reversion. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N 29;23;17;49 34;28;22;54 Env 62 66 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The analysis of P2 genotypes in PBMC cultures indicated that the N139INN deletion in V1 was not sufficient to suppress K601D, but its combination with K601N led to near-WT levels of viral replication . 2013 PLoS pathogens Result HIV K601D;K601N;N139I;N139N 119;151;65;65 124;156;72;72 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The coreceptor activity of WT CCR5 for WT and T138N/L494I/K601N remained at consistently high levels for fusion with BHK21 targets cotransfected with a constant amount of pT4luc vector and a dilution series of pc.CCR5 DNA; the fusion activity of DeltaN139INN/K601N was slightly diminished across the pc.CCR5 dilution series . 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N 58;52;46;259 63;57;51;264 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The DeltaN139INN/K601D and DeltaN139INN/K601N P2 clones exhibited 74-77% of WT fusion activity (P<0.05) with only partial restoration of gp120-gp41 association, even though only the latter clone was competent for replication in PBMCs ( Figs. 2013 PLoS pathogens Result HIV K601D;K601N 17;40 22;45 gp120;gp41 137;143 142;147 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The DeltaN139INN/K601N inhibition curve, however, was shifted by ~1log2 to the left, indicating that this Env is slightly more resistant to sCD4, even though monomeric gp120 containing the DeltaN139INN mutation had similar sCD4 binding characteristics to WT and T138N/L494I. 2013 PLoS pathogens Result HIV K601N;L494I;T138N 17;268;262 22;273;267 gp120;Env 168;106 173;109 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The dominant genotypes in P2 day-50 clones were DeltaN139INN together with K601N, and K601N alone. 2013 PLoS pathogens Result HIV K601N;K601N 75;86 80;91 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The emergence of replication-competent virus at day 40 in the P0 culture correlated with the appearance of L494I in C5 of gp120 (6/6 clones), together with either a D601N pseudoreversion (3/6 clones), and/or T138N, which abolishes a conserved PNGS at position 136 (N136VT) within V1 of gp120 (3/6 clones). 2013 PLoS pathogens Result HIV D601N;L494I;N136T;N136V;T138N 165;107;265;265;208 170;112;271;271;213 gp120;gp120 122;286 127;291 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The gp120 shedding defect did not appear to be associated with a precursor processing defect as Western blotting with the gp41-directed C8 monoclonal antibody (mAb), indicated that similar amounts of gp41 were derived from gp160 for both WT and K601D . 2013 PLoS pathogens Result HIV K601D 245 250 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The K601D mutation was retained in P0 clones isolated at days 20 and 30. 2013 PLoS pathogens Result HIV K601D 4 9 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The N139INN deletion did not provide any improvement to L593V fusogenicity, but restored increasing levels of fusion function to K601D and W596L, respectively. 2013 PLoS pathogens Result HIV K601D;L593V;N139I;N139N;W596L 129;56;4;4;139 134;61;11;11;144 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The N139INN deletion renders fusion function less dependent on Trp596 and Lys601. 2013 PLoS pathogens Result HIV N139I;N139N 4;4 11;11 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The P0 mutations, L494I within C5 and K601N within the DSR, partially restored replication in the PBMCs of one donor but not in the second, apparently less permissive donor . 2013 PLoS pathogens Result HIV K601N;L494I 38;18 43;23 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The pDeltaKAD8env expression vector was next employed to further dissect the functional linkages between position 601 within the DSR, the Asn136 and Asn141/142 PNGS mutations in V1 and the L494I mutation in C5 in gp120-gp41 association and cell-cell fusion assays. 2013 PLoS pathogens Result HIV L494I 189 194 gp120;gp41 213;219 218;223 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The phenotype of T138N/K601D was an outlier as gp120-gp41 association was improved by ~2-fold with respect to K601D without a restorative effect on Env fusion function. 2013 PLoS pathogens Result HIV K601D;K601D;T138N 23;110;17 28;115;22 gp120;gp41;Env 47;53;148 52;57;151 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The restoration of HIV-1AD8-K601D replication competence was observed with sequential passage of cell-free virus in independent PHA-stimulated PBMC cultures . 2013 PLoS pathogens Result HIV K601D 28 33 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The sCD4 EC50 for WT, T138N/L494I and DeltaN139INN gp120 was ~0.5 nM, which approximates the published affinity range of sCD4 for monomeric gp120. 2013 PLoS pathogens Result HIV L494I;T138N 28;22 33;27 gp120;gp120 51;140 56;145 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The suppression of the K601N fusion and replication phenotype by DeltaN139INN is therefore not dependent on the full restoration of gp120-gp41 association or on the L494I C5 mutation. 2013 PLoS pathogens Result HIV K601N;L494I 23;165 28;170 gp120;gp41 132;138 137;142 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The T138N/L494I/K601D and T138N/L494I/K601N genotypes exhibited near-WT replication kinetics in PBMCs from both donors. 2013 PLoS pathogens Result HIV K601D;K601N;L494I;L494I;T138N;T138N 16;38;10;32;4;26 21;43;15;37;9;31 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data indicate that T138N and L494I act cooperatively to restore gp120-gp41 association to K601D with concomitant restoration of membrane fusion function and viral replication competence. 2013 PLoS pathogens Result HIV K601D;L494I;T138N 96;35;25 101;40;30 gp120;gp41 70;76 75;80 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data indicate that T138N in V1 alters the gp120-gp41 association site such that fusion function is less dependent on Trp596 and, when L494I is also present, on Leu593 and Lys601. 2013 PLoS pathogens Result HIV L494I;T138N 140;25 145;30 gp120;gp41 48;54 53;58 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data indicate that the glycosylation site mutations in V1 and L494I in C5 did not alter the CD4-binding ability of monomeric gp120. 2013 PLoS pathogens Result HIV L494I 68 73 gp120 131 136 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data indicate that the K601D and K601N DSR mutations inhibit cell-cell fusion function by destabilizing the gp120-gp41 complex. 2013 PLoS pathogens Result HIV K601D;K601N 29;39 34;44 gp120;gp41 114;120 119;124 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data indicate that the restoration of function to the mutated DSR by the T138N/L494I or DeltaN139INN suppressor mutations in gp120 is unlikely to be a result of altered CD4 and CCR5 utilization. 2013 PLoS pathogens Result HIV L494I;T138N 85;79 90;84 gp120 131 136 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data indicate that the T138N/L494I/K601N reversion mechanism is unlikely to be due to changes in gp120-receptor interactions nor post-receptor binding events such as efficiency of 6-helix bundle formation, whereas DeltaN139INN/K601N may be subtly altered in sCD4-induced changes that inhibit membrane fusion function. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N 41;35;29;233 46;40;34;238 gp120 103 108 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data suggest that T138N, which ablates the PNGS at Asn136 within V1, and L494I act synergistically to suppress K601D (and K601N). 2013 PLoS pathogens Result HIV K601D;K601N;L494I;T138N 117;128;79;24 122;133;84;29 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. These data were reflected in the gp120-gp41 association assay where the shedding phenotype of K601D was restored to wild type and near-wild type levels, respectively, in T138N/L494I/K601N and DeltaN139INN/K601N, in both the presence and absence of kifunensine. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601D;K601N 182;176;170;94;205 187;181;175;99;210 gp120;gp41 33;39 38;43 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Thus L494I/K601D exhibited ~50% of WT cell-cell fusion activity with improved gp120-gp41 association, whereas T138N/L494I/K601D and T138N/L494I/K601N were functionally similar to the WT. 2013 PLoS pathogens Result HIV K601D;K601N;L494I;L494I;T138N;T138N;K601D;L494I 122;144;116;138;110;132;11;5 127;149;121;143;115;137;16;10 gp120;gp41 78;84 83;88 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. To better understand how glycosylation in V1 impacts on gp120-gp41 interactions, we assessed the functional effects of T138N, L494I, T138N/L494I and DeltaN139INN mutations on two other gp120 contact residues within the DSR, Leu593 and Trp596, in addition to Lys601 . 2013 PLoS pathogens Result HIV L494I;L494I;T138N;T138N 126;139;119;133 131;144;124;138 gp120;gp120;gp41 56;185;62 61;190;66 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. To determine how replication was restored to the K601D virus in the long-term PBMC cultures, we reconstructed the dominant P0 and P2 genotypes in the context of the pAD8 proviral clone and examined viral replication in two independent PBMC donors. 2013 PLoS pathogens Result HIV K601D 49 54 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. To this end, we introduced T138N, S143N, S144N, S158N, N160Q and S188N mutations to the WT and K601N pDeltaKADenv vectors and determined their effects on cell-cell fusion, glycoprotein processing and gp120-gp41 association. 2013 PLoS pathogens Result HIV K601N;N160Q;S143N;S144N;S158N;S188N;T138N 95;55;34;41;48;65;27 100;60;39;46;53;70;32 gp120;gp41 200;206 205;210 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. We also compared the abilities of T138N/L494I/K601N, DeltaN139INN/K601N and WT Envs to mediate cell-cell fusion with the CCR5-Y14N tyrosine sulfation mutant, which exhibits a lower affinity for gp120-gp41 and functions as a HIV-1 coreceptor in a cell surface concentration-dependent manner. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N 46;40;34;66 51;45;39;71 gp120;gp41;Env 194;200;79 199;204;83 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. We also noted that the L494I mutation in a WT background did not substantially increase cell-cell fusion or gp120-gp41 association (data not shown). 2013 PLoS pathogens Result HIV L494I 23 28 gp120;gp41 108;114 113;118 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. We first confirmed that the K601D mutation promoted the shedding of gp120 into the culture supernatant of 293T cells transfected with pcDNA3.1-AD8env, as determined by radioimmunoprecipitation . 2013 PLoS pathogens Result HIV K601D 28 33 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. We next compared the sensitivity of T138N/L494I/K601N-, DeltaN139INN/K601N- and WT-Env-mediated fusion to inhibition with sCD4. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N 48;42;36;69 53;47;41;74 Env 83 86 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. We next examined the effects of 10 microM kifunensine on the cell-cell fusion activities of the T138N/L494I/K601N and DeltaN139INN/K601N revertant Envs. 2013 PLoS pathogens Result HIV K601N;L494I;T138N;K601N 108;102;96;131 113;107;101;136 Env 147 151 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. We therefore asked if the mutations in gp120 and K601N led to changes in sensitivity to the HR2 synthetic peptide analogue, C34, which blocks fusion by binding to the coiled coil of HR1 helices in a receptor-triggered prehairpin intermediate conformation of gp41. 2013 PLoS pathogens Result HIV K601N 49 54 gp120;gp41 39;258 44;262 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. We therefore asked whether the T138N and DeltaN139INN mutations were linked to changes in the neutralization sensitivity of Env-pseudotyped reporter viruses. 2013 PLoS pathogens Result HIV T138N 31 36 Env 124 127 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. While L593V and K601D mutations resulted in decreased gp120-gp41 association and cell-cell fusion function, the W596L mutant exhibited WT levels of gp120-gp41 association but reduced cell-cell fusion by ~40% at subsaturating Env (P<0.02, 2 sample t-test, unequal variances) . 2013 PLoS pathogens Result HIV K601D;L593V;W596L 16;6;112 21;11;117 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Also when L30E mutation was accompanied with DeltaVpu, we did not observe much difference in the infectivity of double mutant and DeltaVpu viruses from HeLa cells. 2013 PloS one Result HIV L30E 10 14 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Also, double mutant (L30E-DeltaVpu) viruses possessed increased amount of Env than DeltaVpu viruses from all cell types except HeLa cells where the amount of Env was similar in L30E-DeltaVpu and DeltaVpu and therefore was the reason of similar infectivity. 2013 PloS one Result HIV L30E;L30E 21;177 25;181 Env;Env 74;158 77;161 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Also, mutation in gag MA (L30E) did not affect expression of Gag p24 and Gag p55 proteins. 2013 PloS one Result HIV L30E 26 30 p24;Gag;Gag;Gag;Matrix 65;18;61;73;22 68;21;64;76;24 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. As evident from Figure 4B, at day 12, the infectivity of L30E-DeltaVpu double mutant viruses was found to be significantly more than L30E and DeltaVpu mutant viruses. 2013 PloS one Result HIV L30E;L30E 57;133 61;137 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. As expected, the level of Env (gp41) on L30E viruses from all cell-types was significantly low as compared to wild-type. 2013 PloS one Result HIV L30E 40 44 gp41;Env 31;26 35;29 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. As shown in Figure 3A, we found that point mutation in Gag MA (L30E) did not affect particle release in any of the cell type used to prepare viruses. 2013 PloS one Result HIV L30E 63 67 Gag;Matrix 55;59 58;61 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. As shown in Figure 6A, infectivity of all primary envelopes was reduced in absence of Vpu; however when Gag L30E mutation was accompanied with Vpu start codon mutation, significant improvement in infectivity of patient envelopes was observed (Figure 6D). 2013 PloS one Result HIV L30E 108 112 Env;Env;Vpu;Vpu;Gag 50;219;86;143;104 59;228;89;146;107 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Based on observations that proposed the role of Gag MA in Vpu-mediated particle release, we next examined whether there is any alteration in Vpu mediated particle release and infectivity due to a specific point mutation in Gag MA (L30E) that was previously shown to severely diminish virus infectivity and Env incorporation and whether it is dependent on cell-type. 2013 PloS one Result HIV L30E 231 235 Vpu;Vpu;Env;Gag;Gag;Matrix;Matrix 58;141;306;48;223;52;227 61;144;309;51;226;54;229 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. But in the absence of Vpu (DeltaVpu and L30E-DeltaVpu), a significant fraction of Env was found localized at plasma membrane. 2013 PloS one Result HIV L30E 40 44 Vpu;Env 22;82 25;85 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Cells were transfected on cover slips with four different constructs (WT, DeltaVpu, L30E, L30E-DeltaVpu) and 36 h after transfection, cells were fixed, permeabilized and immunolabeled with anti-Env monoclonal antibody 2F5. 2013 PloS one Result HIV L30E;L30E 84;90 88;94 Env 194 197 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Effect of Vpu Start Codon Mutation in Restoring Gag L30E Defect Verified in Unrelated Patient-derived Envelopes of Diverse Origin. 2013 PloS one Result HIV L30E 52 56 Env;Vpu;Gag 102;10;48 111;13;51 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Env Incorporation Defect Caused by Gag Matrix L30E Mutation was Partially Rescued by Vpu Start Codon Mutation. 2013 PloS one Result HIV L30E 46 50 Matrix;Vpu;Env;Gag 39;85;0;35 45;88;3;38 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. In addition, we noticed significant difference between infectivity potential of DeltaVpu and L30E-DeltaVpu viruses from all cell types except HeLa cells where the infectivity of DeltaVpu and L30E-DeltaVpu was similar. 2013 PloS one Result HIV L30E;L30E 93;191 97;195 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. In contrast, in 293T cells we found Env was diffusely present throughout the cytoplasm in WT, DeltaVpu and L30E-DeltaVpu, (data not shown). 2013 PloS one Result HIV L30E 107 111 Env 36 39 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. In marked contrast, though the level of virus release of double mutant (L30E-DeltaVpu) was less than the L30E variant but the amount of Env incorporation on released virion particles was comparatively more than L30E viruses, thus, contributing to enhanced infectivity of L30E-DeltaVpu viruses (Figure 3C). 2013 PloS one Result HIV L30E;L30E;L30E;L30E 72;105;211;271 76;109;215;275 Env 136 139 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. In marked contrast, we found enhancement in the infectivity potential of double mutant virus (L30E-DeltaVpu) indicating that inactivation of Vpu restored infectivity of L30E mutant viruses. 2013 PloS one Result HIV L30E;L30E 94;169 98;173 Vpu 141 144 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Infectious virion assay showed that L30E viruses displayed diminished infectivity irrespective of the cell type used for production of viruses and was in accordance with previous reports (Figure 3B). 2013 PloS one Result HIV L30E 36 40 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Infectivity in TZM-bl cells using equal RT units showed 40% increase in infectivity level of L30E-DeltaVpu viruses as compared to DeltaVpu viruses (Figure 8D). 2013 PloS one Result HIV L30E 93 97 RT 40 42 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Instead, virus release of Gag L30E mutant was consistently greater than wild-type in 293T and HeLa cells and comparable in NP2 and GHOST cells. 2013 PloS one Result HIV L30E 30 34 Gag 26 29 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Interestingly, double mutant viruses (L30E-DeltaVpu) replicated efficiently in both PBMC and MDM, though their release was 50% less as compared to wild-type. 2013 PloS one Result HIV L30E 38 42 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Introduction of Vpu Start Codon Mutation in pNL-AD8 with L30E Substitution Modulated Virus Infectivity and Particle Release. 2013 PloS one Result HIV L30E 57 61 Vpu 16 19 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. L30E viruses which were defective in envelope incorporation replicated neither in PBMC nor in MDM in either of the donor. 2013 PloS one Result HIV L30E 0 4 Env 37 45 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Molecular constructs possessing Gag MA mutation L30E (Leucine replaced with Glutamic acid at 30th position) with and without Vpu start codon mutation were made to study the combined effect of both mutations on virus replication and infectivity. 2013 PloS one Result HIV L30E 48 52 Vpu;Gag;Matrix 125;32;36 128;35;38 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Nonetheless, the release of L30E-DeltaVpu viruses was similar to DeltaVpu in HeLa cells but was significantly less than WT and L30E mutant. 2013 PloS one Result HIV L30E;L30E 28;127 32;131 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Our results indicated that disrupting BST-2 expression by siRNA in HeLa cells not only restored the release of DeltaVpu viruses but further alleviated the infectivity of double mutant viruses (L30E-DeltaVpu) and this rescue of infectivity of the L30E mutant by Vpu inactivation is most likely due to enhanced envelope incorporation. 2013 PloS one Result HIV L30E;L30E 193;246 197;250 Env;Vpu 309;261 317;264 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Overall, our findings show that the abrogation of virus growth and infectivity due to Gag L30E mutation was rescued by Vpu inactivation in primary cells also. 2013 PloS one Result HIV L30E 90 94 Vpu;Gag 119;86 122;89 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Results showed that knockdown of endogenous BST-2 led to more than 3 fold increases in the total amount of virus release of DeltaVpu and L30E-DeltaVpu as quantified by RT ELISA (Figure 8C). 2013 PloS one Result HIV L30E 137 141 RT 168 170 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Significant reduction in particle release of DeltaVpu and double mutant (L30E-DeltaVpu) was monitored from HeLa cells as compared to 293T, NP2 and GHOST cells. 2013 PloS one Result HIV L30E 73 77 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Taken together, this data clearly indicates that inactivation of vpu by start codon mutation was found beneficial in rescuing the defect of Gag L30E mutation. 2013 PloS one Result HIV L30E 144 148 Vpu;Gag 65;140 68;143 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. The enhanced infectivity of double mutant (L30E-DeltaVpu) varied between 3 to 7 fold among different cell types (293T, HeLa, NP2 and GHOST) in comparison to L30E mutant. 2013 PloS one Result HIV L30E;L30E 43;157 47;161 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. The enhancement in infectivity of L30E-DeltaVpu viruses was less than wild-type but significantly higher than their L30E counterpart. 2013 PloS one Result HIV L30E;L30E 34;116 38;120 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. The Env of Gag L30E mutant was detected mainly near the perinuclear compartment and away from the plasma membrane. 2013 PloS one Result HIV L30E 15 19 Env;Gag 4;11 7;14 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Therefore, we further investigated whether inactivation of Vpu could alter the release and infectivity of Gag MA (L30E) mutants in primary cells that are natural targets of HIV-1 in vivo, such as peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM). 2013 PloS one Result HIV L30E 114 118 Vpu;Gag;Matrix 59;106;110 62;109;112 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. These results suggested that inactivation of Vpu by introducing start codon mutation partially restored Env incorporation defect of Gag L30E mutants and hence improved their infectivity phenotype. 2013 PloS one Result HIV L30E 136 140 Vpu;Env;Gag 45;104;132 48;107;135 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. This data and the immunofluorescence data together indicate that BST-2 host factor might be responsible for restricted release of DeltaVpu and L30E-DeltaVpu viruses in HeLa cells. 2013 PloS one Result HIV L30E 143 147 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. This decrease in the level of gp41 incorporated onto virions resulted in diminished infectivity of L30E viruses. 2013 PloS one Result HIV L30E 99 103 gp41 30 34 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. This further suggested that the effect of Vpu inactivation in restoring envelope incorporation defect of L30E viruses is universal and irrespective of viral strain, however the level of effect may vary from strain to strain. 2013 PloS one Result HIV L30E 105 109 Env;Vpu 72;42 80;45 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. This result suggests that the infectivity of defective L30E viruses was significantly alleviated by inactivation of vpu gene. 2013 PloS one Result HIV L30E 55 59 Vpu 116 119 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. To address this, PBMC and MDM were obtained from two HIV-1 seronegative healthy donors and infected with equal infectious units of VSV-G pseudotyped viruses (WT, DeltaVpu, L30E and L30E-DeltaVpu). 2013 PloS one Result HIV L30E;L30E 172;181 176;185 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. To answer this question, we used siRNA oligonucleotides to deplete endogenous BST-2 in HeLa cells and then transfected siRNA treated cells with WT, DeltaVpu, L30E and L30E-DeltaVpu DNA. 2013 PloS one Result HIV L30E;L30E 158;167 162;171 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. To test this hypothesis, 293T, HeLa, NP2 and GHOST cells were transfected with pNL-AD8 (WT) plasmid and its mutant derivatives (DeltaVpu, L30E and L30E-DeltaVpu). 2013 PloS one Result HIV L30E;L30E 138;147 142;151 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Vpu Start Codon Mutation Restored Infectivity and Replication Defect of Gag (L30E) Mutant Viruses in PBMC and Monocyte-derived Macrophages. 2013 PloS one Result HIV L30E 77 81 Vpu;Gag 0;72 3;75 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. We found infectivity of the VSV-G pseudotyped viruses (all WT and mutants) was unaffected and all Vpu and Gag L30E mutants were showing infectivity similar to WT (Figure S1). 2013 PloS one Result HIV L30E 110 114 Vpu;Gag 98;106 101;109 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. We further examined whether loss of Vpu expression has any association between modulations of infectivity of L30E viruses with Env incorporation on released virion particles. 2013 PloS one Result HIV L30E 109 113 Vpu;Env 36;127 39;130 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. We next verified whether the effect of Vpu start codon mutation on L30E mediated infectivity defect was specific to lab-adapted pNL-AD8 construct or equally effective in primary HIV-1 envelopes of diverse origin derived from patients. 2013 PloS one Result HIV L30E 67 71 Env;Vpu 184;39 193;42 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. A D601H pseudoreversion emerged at day 10 (2/6 clones, WL/KH) prior to the appearance of D674E in the MPER at day 20, which persisted throughout the culture period. 2013 Retrovirology Result HIV D601H;D674E 2;89 7;94 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. At day 10, 3/6 clones contained WL/KH, while 3 others contained the Thr-394-Trp-395 deletion in V4 (DeltaTW), together with W596L and D601H in the DSR, and D674N in the MPER (DeltaTW/WL/KH/DN). 2013 Retrovirology Result HIV D601H;D674N;W596L 134;156;124 139;161;129 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Consistent with the cell-free virus infectivity data, WL/KD blocked cell-cell fusion, WL/KH exhibited partially restored fusion function and D674N and D674G mutations were inhibitory in a WL/KH context (Figure 6). 2013 Retrovirology Result HIV D674G;D674N 151;141 156;146 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Figure 5B again confirms the gp120 shedding defect of WL/KD and indicates that the subsequent D601H mutation, present in the WL/KH clone was sufficient to partially restore gp120 association levels with no further improvements to association following the addition of 2nd and 3rd site mutations. 2013 Retrovirology Result HIV D601H 94 99 gp120;gp120 29;173 34;178 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. However, in contrast to the infectivity data, D674E did not enhance fusogenicity when added to WL/KH. 2013 Retrovirology Result HIV D674E 46 51 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. In the case of WLKD-1, cell-free virus-initiated replication in U87.CD4.CCR5 cells was partially restored by D601H in the DSR (WL/KH) and was optimised further by D674E in the MPER (WL/KH/DE) (Figure 3A). 2013 Retrovirology Result HIV D601H;D674E 109;163 114;168 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Notably, the presence of D674N was not inhibitory to replication when combined with WL/KH in this infection system. 2013 Retrovirology Result HIV D674N 25 30 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The addition of D674G to WL/KH (WL/KH/DG) markedly suppressed viral entry consistent with the observed lack of replication. 2013 Retrovirology Result HIV D674G 16 21 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The addition of L85M to WL/KH/DE did not improve replication any further. 2013 Retrovirology Result HIV L85M 16 20 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The alternate MPER mutation, D674N, was inhibitory on the WL/KH background, consistent with the relative replicative capacity of WL/KH/DN and WL/KH, while the addition of DeltaTW to WL/KH/DN did not improve single-cycle entry competence any further. 2013 Retrovirology Result HIV D674N 29 34 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The D601H pseudoreversion in WL/KH increased this infectivity by ~10-fold while the addition of D674E led to a further 2-fold improvement, but the entry competence of WL/KH/DE remained 20-fold lower than WT. 2013 Retrovirology Result HIV D601H;D674E 4;96 9;101 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The data show that D674E and D674N did not affect cell-free or cell-cell viral transmission (Figure 4D and E, respectively). 2013 Retrovirology Result HIV D674E;D674N 19;29 24;34 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The functional advantages conferred by D601H and D674E were less obvious in the single cycle infectivity assay when compared to 14-day replication experiments (compare Figure 3A, B and C). 2013 Retrovirology Result HIV D601H;D674E 39;49 44;54 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The G145E V1 mutation observed at days 30-40 did not confer a replication advantage to WL/KH/DN. 2013 Retrovirology Result HIV G145E 4 9 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The genotypes observed over the 50-day culture period included WL/KH (9/35 clones), W596L/K601H/D674E (WL/KH/DE [10/35 clones]), L85M/W596L/K601H/D674E (LM/WL/KH/DE [6/35 clones]), W596L/K601H/D674G (WL/KH/DG [4/35 clones]), L85M/W596L/K601H (LM/WL/KH [1/35 clones]), and W596L/K601H/D674N (WL/KH/DN [1/35 clones]) (Figure 2C). 2013 Retrovirology Result HIV D674E;D674E;D674G;D674N;K601H;K601H;K601H;K601H;K601H;L85M;L85M;W596L;W596L;W596L;W596L;W596L 96;146;193;284;90;140;187;236;278;129;225;84;134;181;230;272 101;151;198;289;95;145;192;241;283;133;229;89;139;186;235;277 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The K601H and D674E mutations were not observed in env clones obtained following passaging of the WT virus, while D674N was observed in 1 clone (data not shown). 2013 Retrovirology Result HIV D674E;D674N;K601H 14;114;4 19;119;9 Env 51 54 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The W596L mutation was retained in 70/71 env clones obtained from the WLKD-1 and WLKD-2 cultures indicating a strong selection pressure to maintain Leu at 596. 2013 Retrovirology Result HIV W596L 4 9 Env 41 44 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The WL/KD mutation led to > 95% of total gp120 being sloughed into the culture supernatant (Figure 1B) indicating a shedding phenotype that was more severe than those of the component single K601D and W596L mutants. 2013 Retrovirology Result HIV K601D;W596L 191;201 196;206 gp120 41 46 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. These data suggest that D601H and D674E can act synergistically to suppress the original replication defect. 2013 Retrovirology Result HIV D601H;D674E 24;34 29;39 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. These data suggest that the D601H pseudoreversion and 2nd (and 3rd) site mutations optimise viral spread mediated by cell-associated virus. 2013 Retrovirology Result HIV D601H 28 33 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Thus D674N is inhibitory to cell-free virus initiated replication in the context of WL/KH with DeltaTW partially relieving this inhibition. 2013 Retrovirology Result HIV D674N 5 10 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. We next determined if the modulation of infectivity by D674E, D674N and D674G occurred via a functional link to Leu-596 and His-601 or whether it could be explained by a generalized enhancement or inhibition in Env function. 2013 Retrovirology Result HIV D674E;D674G;D674N 55;72;62 60;77;67 Env 211 214 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. We next determined whether D674E and D674N on a WT HIV-1AD8 background had any effect on cell-free or cell-associated viral transmission in 10-day U87.CD4.CCR5 cultures. 2013 Retrovirology Result HIV D674E;D674N 27;37 32;42 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. [3H]DA uptake in Y470H-hDAT was 19% of that in WT hDAT in cells transfected with equal amount of plasmid DNA for WT and mutated DAT, which is consistent with the low DAT expression observed in. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 17 22 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. 3A, the Y470H-hDAT displayed a decrease in the Vmax values (2.8 +- 0.8 pmol/min/105 cells) compared with WT hDAT [15.7 +- 0.9 pmol/min/105 cells; t(3) = 15.6, p<0.001, unpaired Student's t test]; no difference in the Km values was observed. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 8 13 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. 3B, despite no difference in the ratio of surface DAT to total DAT between WT and Y470-hDAT (biotinylated/total: WT, 0.70 +- 0.06; and Y470H, 0.68 +- 0.1; p >0.05, one-way ANOVA), the absolute surface DAT in the mutant hDAT was decreased slightly compared to WT hDAT (unpaired Student's t test). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 135 140 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. 4A); however, no effect of Tat was observed in Y470H-hDAT (F(1, 12) = 0.05; p > 0.05), suggesting that mutation of Tyr470 in hDAT attenuates Tat-induced reduction of hDAT function. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 47 52 Tat;Tat 27;141 30;144 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. A mutation in hDAT (tyrosine to histidine, Y470H-hDAT) was generated by site-directed mutagenesis. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 43 48 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. A subsequent simple effect analysis revealed a dramatic decrease (80%) in [3H]DA uptake in Y470H-hDAT (F(1, 12) = 25; p < 0.001) compared to WT hDAT in the absence of Tat. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 91 96 Tat 167 170 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. A two-way ANOVA on the specific [3H]WIN35,428 binding in WT and Y470H-hDAT revealed a significant main effect of mutation (F(1, 24) = 6.5; p < 0.05), zinc (F(1, 24) = 4.3; p < 0.05) and a significant mutation x zinc interaction (F(1, 24) = 4.2; p < 0.05). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 64 69 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Although a lower magnitude of DA efflux in response to Tat treatment was found in WT hDAT in comparison to DA efflux in Y470H-hDAT. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 120 125 Tat 55 58 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. As shown in Figure 4A, two-way ANOVA on the specific [3H]DA uptake in WT and Y470H-hDAT revealed a significant main effect of mutation (F(1, 24) = 6.5; p < 0.05), Tat treatment (F(1, 24) = 7.5; p < 0.05) and a significant mutation x Tat interaction (F(1, 24) = 8.9; p < 0.05). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 77 82 Tat;Tat 163;233 166;236 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Exposure to Tat1-86 decreased [3H]DA uptake by 38% in WT hDAT (F(1, 12) = 12.8; p < 0.01); however, no effect of Tat on [3H]DA uptake was observed in Y470H-hDAT. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 150 155 Tat;Tat 12;113 15;116 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. For these experiments, CHO cells expressing WT and Y470H-hDAT were treated with 10 muM ZnCl2 and assayed for both [3H]DA uptake and [3H]WIN 35,428. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 51 56 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. However, the potencies of cocaine and GBR12909 for inhibition of [3H]DA uptake were ~3.5-fold greater in Y470H-hDAT as compared with WT hDAT (unpaired Student's t test). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 105 110 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Similarly, exposure to recombinant Tat1-86 decreased Vmax by 35% and 6% in WT hDAT and Y470H-hDAT, respectively. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 87 92 Tat 35 38 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Since DA uptake is linear with DAT expression, in order to rule out whether the lack of effect of Tat on DA uptake in this mutant hDAT is due to a low DAT expression level in Y470H-hDAT relative to WT hDAT, we corrected the Vmax value of Y470H-hDAT to 40% of that in WT hDAT using 3x amount of plasmid Y470H DNA in transfection. 2013 Journal of neuroimmune pharmacology Result HIV Y470H;Y470H;Y470H 175;238;302 180;243;307 Tat 98 101 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. The addition of Zn2+ decreased [3H]DA uptake in WT and Y470H-hDAT by 89% versus 32%, respectively. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 55 60 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. The apparent affinity (IC50) for DA was not significantly different between the WT hDAT (895 +- 80 nM) and Y470H-hDAT (737 +- 72 nM). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 107 112 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Thus, the reduction of available DAT on the cell surface may also partially contribute to the decreased DA uptake actually measured in Y470H-hDAT, relative to WT DAT. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 135 140 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To assess whether the decreased Vmax in this mutant was caused by decreased surface DAT expression, we determined DAT surface expression in CHO cells transfected with WT or Y470H-hDAT using cell surface biotinylation. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 173 178 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To determine whether the mutation of Tyr470 alters inhibitory effects of Tat on DA uptake, we examined the specific [3H]DA uptake in WT hDAT and Y470H-hDAT in the presence or absence of released Tat1-72 (1 ng/ml) or recombinant Tat1-86 (350 nM). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 145 150 Tat;Tat;Tat 73;195;228 76;198;231 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To explore the potential relationship between the binding sites of Tat in DAT and the binding sites of DAT substrate and inhibitors, we also tested the ability of DA, cocaine and GBR12909 to inhibit [3H]DA uptake in WT hDAT and Y470H-hDAT (Table 1). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 228 233 Tat 67 70 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To further determine the role of Y470H-hDAT in the transition between outward-facing and inward-facing states, we also examined basal DA efflux in WT hDAT and this mutant. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 33 38 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. two-way ANOVA on the specific [3H]DA uptake in WT and Y470H-hDAT revealed a significant main effect of mutation (F(1, 24) = 11.5; p < 0.05), zinc (F(1, 24) = 9.1; p < 0.05) and a significant mutation x zinc interaction (F(1, 24) = 9.9; p < 0.05). 2013 Journal of neuroimmune pharmacology Result HIV Y470H 54 59 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Zn2+ caused a 40% increase in [3H]WIN 35,428 binding in WT but had no effect on Y470H-hDAT. 2013 Journal of neuroimmune pharmacology Result HIV Y470H 80 85 23660583 Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay. Slightly more V106M, Y181C, and G190A mutants were detected by MPX- compared to SPX-OLA across the filter paper and plasma specimens. 2013 Journal of virological methods Result HIV G190A;V106M;Y181C 32;14;21 37;19;26 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. IN_in containing the inactivation mutation D64V could perform neither 3'-processing nor strand transfer, but possessed an exonucleolytic activity. 2013 PloS one Result HIV D64V 43 47 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. Inactive IN was further supplemented with mutations H51Y, E92Q, S147G, and K160Q, conferring resistance to elvitegravir and a polymorphic mutation E157Q common for subtype A, which yielded IN_e3 (D64V+H51Y, E92Q, S147G, E157Q, K160Q). 2013 PloS one Result HIV D64V;E157Q;E157Q;E92Q;E92Q;H51Y;H51Y;K160Q;K160Q;S147G;S147G 196;147;220;58;207;52;201;75;227;64;213 200;152;225;62;211;56;205;80;232;69;218 IN 9 11 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. However, I84V was also observed in 0.32% of control samples, indicating that it cannot necessarily be concluded that it was directly selected by atazanavir. 2013 The Journal of antimicrobial chemotherapy Result HIV I84V 9 13 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. In almost all patients in whom a baseline resistance test was available, the common M36I and L63P polymorphisms pre-existed prior to exposure to atazanavir. 2013 The Journal of antimicrobial chemotherapy Result HIV L63P;M36I 93;84 97;88 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Only 6 (1.9%) index patients experiencing virological failure had a major atazanavir-associated mutation, all in isolation: I50L (n = 3), I84V (n = 2) and N88S (n = 1) (Table 2). 2013 The Journal of antimicrobial chemotherapy Result HIV I50L;I84V;N88S 124;138;155 128;142;159 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Specifically, none of the patients who were observed to have I15S, K43T, I50L, V82T, I84V, N88S or L89V mutations at virological failure had a baseline resistance test. 2013 The Journal of antimicrobial chemotherapy Result HIV I15S;I50L;I84V;K43T;L89V;N88S;V82T 61;73;85;67;99;91;79 65;77;89;71;103;95;83 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. The remaining 43 minor atazanavir mutations were either not detected in this dataset (L10C, K20V, E34Q, F53Y, I54L/M/T/A, A71L, G73C/T, V82F and I93M) or were not significantly associated with atazanavir exposure (L10I/F/V, G16E, K20R/M/I/T, L24I, V32I, L33I/F/V, M36L/V, M46L, G48V, I54V, D60E, I62V, I64L/M/V, A71I/T, G73S/A, V82A/I, L90M and I93L). 2013 The Journal of antimicrobial chemotherapy Result HIV A71I;A71L;A71T;D60E;E34Q;F53Y;G16E;G48V;G73A;G73C;G73S;G73T;I54A;I54L;I54M;I54T;I54V;I62V;I64L;I64M;I64V;I93L;I93M;K20I;K20M;K20R;K20T;K20V;L10C;L10F;L10I;L10V;L24I;L33F;L33I;L33V;L90M;M36L;M36V;M46L;V32I;V82A;V82F;V82I 312;122;312;290;98;104;224;278;320;128;320;128;110;110;110;110;284;296;302;302;302;345;145;230;230;230;230;92;86;214;214;214;242;254;254;254;336;264;264;272;248;328;136;328 318;126;318;294;102;108;228;282;326;134;326;134;120;120;120;120;288;300;310;310;310;349;149;240;240;240;240;96;90;222;222;222;246;262;262;262;340;270;270;276;252;334;140;334 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Although substitutions in gp120, represented by F277V, might contribute to the resistance to a high concentration of B404, 20 passages were required for the emergence of these substitutions. 2013 Frontiers in microbiology Result HIV F277V 48 53 gp120 26 31 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Analysis of viral proteins in cells and supernatants from transfected 293T cells revealed that incorporation of Env into virions was significantly high in SS and NS viruses with the Q733stop substitution (Figure 5). 2013 Frontiers in microbiology Result HIV Q733X 182 190 Env 112 115 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Another stop codon (W782stop) was the second major mutation, which was detected after 17 passages. 2013 Frontiers in microbiology Result HIV W782X 20 28 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Group 26II was clearly distinguished from group 26I by amino acid substitutions, such as T136M, N295S, and D571M/E (Table 1), suggesting two lineages of variants in P26B404. 2013 Frontiers in microbiology Result HIV D571E;D571M;N295S;T136M 107;107;96;89 114;114;101;94 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. In addition to these substitutions, most of clones acquired the F277V substitution in the late stage of evolution, except for one group at passage 26 which has the N295S substitution (see Figure 1, group 26II). 2013 Frontiers in microbiology Result HIV F277V;N295S 64;164 69;169 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Neutralization by anti-V2 MAb M318T was even enhanced in SN, although NS showed the resistance comparable to those of SS and P26B404. 2013 Frontiers in microbiology Result HIV M318T 30 35 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Point mutants with substitutions F277V and N295S, which were representative mutations at late passages, were also constructed by PCR mutagenesis. 2013 Frontiers in microbiology Result HIV F277V;N295S 33;43 38;48 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Resistance to neutralization was not significantly detected by the point mutants F277V and N295S, except for the neutralization of F277V by K8 (4.3-fold decrease of IC50 value). 2013 Frontiers in microbiology Result HIV F277V;F277V;N295S 81;131;91 86;136;96 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. SS and NS were predicted to have a truncated gp41 with no other mutation in gp41, because the Q733stop substitution was the first substitution in gp41. 2013 Frontiers in microbiology Result HIV Q733X 94 102 gp41;gp41;gp41 45;76;146 49;80;150 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Substitutions V17L in the signal peptide and E176K in the V2 loop emerged after 20 and 23 passages, respectively, although the E176K substitution was also observed in P26C, control viruses after 26 passages in the absence of B404 (Table 1). 2013 Frontiers in microbiology Result HIV E176K;E176K;P26C;V17L 45;127;167;14 50;132;171;18 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. The decrease of MPI values for NS suggested that truncation of gp41 by the Q733stop substitution, the first major substitution in viral evolution, was important to escape from the neutralizing antibodies. 2013 Frontiers in microbiology Result HIV Q733X 75 83 gp41 63 67 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. The env region of SIVmac316 was replaced by that of P26B404 clone 26, which had substitutions typical to the P26I group. 2013 Frontiers in microbiology Result HIV P26I 109 113 Env 4 7 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. The Q733stop substitution in the gp41 cytoplasmic domain was observed in 12 of 14 clones at passage 8 and in all clones thereafter. 2013 Frontiers in microbiology Result HIV Q733X 4 12 gp41 33 37 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. The Q733stop substitution, the first major mutation during passages in the presence of B404, might be selected because it facilitates adaptation of virus to human cells and imparts resistance to antibody. 2013 Frontiers in microbiology Result HIV Q733X 4 12 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. The virus recovered at passage 26 (P26B404) was resistant to neutralization by B404 (V3/V4) and other antibodies, MAbs K8 (CD4i) and M318T (V2), that target epitopes other than that recognized by B404. 2013 Frontiers in microbiology Result HIV M318T 133 138 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. These mutant viruses were examined for their sensitivity to neutralization by three MAbs B404 (V3/V4 conformational), K8 (CD4i), and M318T (V2). 2013 Frontiers in microbiology Result HIV M318T 133 138 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. These results indicate that gp41 truncation by the Q733stop substitution contributes to neutralization resistance of viruses in macaque cells. 2013 Frontiers in microbiology Result HIV Q733X 51 59 gp41 28 32 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. These results indicate that truncation of gp41 caused by the Q733stop substitution increases viral infectivity for human cells. 2013 Frontiers in microbiology Result HIV Q733X 61 69 gp41 42 46 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. These results suggest that truncation of gp41 by the Q733stop substitution enhances incorporation of Env into virions. 2013 Frontiers in microbiology Result HIV Q733X 53 61 gp41;Env 41;101 45;104 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. Another 2 (1.8%) presented the M184V mutation to nucleoside reverse transcriptase inhibitors (NRTI). 2013 PloS one Result HIV M184V 31 36 NRTI;NRTI 49;94 81;98 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. For NRTI-resistance, the mutation M184V was found in all 3 cases. 2013 PloS one Result HIV M184V 34 39 NRTI 4 8 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. In 5 (3.4%) subjects, the mutations affected PR inhibitors (PI), with M46I/L substitution in all cases. 2013 PloS one Result HIV M46I;M46L 70;70 76;76 PI;PR 60;45 62;47 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. The highest rate (27.8%) was found for NNRTI-resistance due to mutation K103N in 3 of the 7 cases. 2013 PloS one Result HIV K103N 72 77 NNRTI 39 44 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. The PI-resistance mutations found were M46L (4 cases), and L90M and I84V (3 cases each). 2013 PloS one Result HIV I84V;L90M;M46L 68;59;39 72;63;43 PI 4 6 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. A majority (86.2%; n=25) of participants with VF at their baseline visit had an M184V mutation. 2013 Journal of the International AIDS Society Result HIV M184V 80 85 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Additionally, two participants were found to have the 69 insertion site mutation, and four more patients had K65R or K70E. 2013 Journal of the International AIDS Society Result HIV K65R;K70E 109;117 113;121 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. During this time, seven additional participants developed M184V, three developed 69 insertion site mutations and two developed Q151M. 2013 Journal of the International AIDS Society Result HIV M184V;Q151M 58;127 63;132 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Mutation patterns among the 13 participants with VF and IF detected at the same time were also examined and found to be comparable to the mutation patterns at the end of the study for the 44 participants with VF but no IF: 9 of the 13 participants (69.2%) had the M184V mutation; six (46.2%) had any TAMs, with a majority having 3 or more TAMs; 8 (61.5%) had predicted resistance to tenofovir; and 9 (69.2%) had an etravirine mutation score >=2.5. 2013 Journal of the International AIDS Society Result HIV M184V 264 269 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Seven (24.1%) had K103N, seven (24.1%) had G190A and six (20.7%) had K101E. 2013 Journal of the International AIDS Society Result HIV G190A;K101E;K103N 43;69;18 48;74;23 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. The only NRTI mutation detected in any of these participants was M184V, with eight of the 15 patients (53.3%) harbouring this mutation. 2013 Journal of the International AIDS Society Result HIV M184V 65 70 NRTI 9 13 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. There were a few NNRTI mutations present: two patients had Y181C, two had K103N, five had G190A and one had K101E. 2013 Journal of the International AIDS Society Result HIV G190A;K101E;K103N;Y181C 90;108;74;59 95;113;79;64 NNRTI 17 22 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. When the evolution of NNRTI mutations was assessed, three more participants developed K103N, two more developed Y181C, and six more each developed G190A and K101E. 2013 Journal of the International AIDS Society Result HIV G190A;K101E;K103N;Y181C 147;157;86;112 152;162;91;117 NNRTI 22 27 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. With regard to NNRTI mutations, more than one-half of the participants with VF at enrolment (51.7%; n=15) had Y181C owing to the prevalence of nevirapine use in first-line regimens. 2013 Journal of the International AIDS Society Result HIV Y181C 110 115 NNRTI 15 20 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Among individuals with positive AS-PCR for the K65R mutation and with negative consensus sequencing, the median DeltaCT value was 7.4 (IQR: 6.9, 7.4); close to the threshold representing 2% of quasi-species. 2013 Antiviral therapy Result HIV K65R 47 51 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Among those with the K65R identified only with AS-PCR, two had received prior d4T, one prior AZT, and two had no history of ART prior to TDF initiation. 2013 Antiviral therapy Result HIV K65R 21 25 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. AS-PCR identified the presence of M184V in 10 patients (9 identified by sequencing and one additional patient). 2013 Antiviral therapy Result HIV M184V 34 39 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Five (12%; 95% confidence interval: 4.1-27%) patients had the K65R mutation, four of whom also had the M184V mutation. 2013 Antiviral therapy Result HIV K65R;M184V 62;103 66;108 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Four of the five samples that had the K65R mutation by sequencing also had the K65R mutation detected by AS-PCR (the fifth had insufficient volume for AS-PCR); in addition, five patients who were negative for the K65R by sequencing were positive by AS-PCR. 2013 Antiviral therapy Result HIV K65R;K65R;K65R 38;79;213 42;83;217 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. NNRTI mutations were the most common (; 52%), followed by the M184V/I mutation (, 28%; 10 with M184V and 1 with M184I). 2013 Antiviral therapy Result HIV M184I;M184I;M184V;M184V 62;112;62;95 69;117;69;100 NNRTI 0 5 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. No K70E mutations were detected by AS-PCR. 2013 Antiviral therapy Result HIV K70E 3 7 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. No patients had the K70E by population sequencing. 2013 Antiviral therapy Result HIV K70E 20 24 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. One sample had insufficient volume for AS-PCR; a sample that contained the K65R and M184V mutations by consensus sequencing. 2013 Antiviral therapy Result HIV K65R;M184V 75;84 79;89 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. The five patients with the K65R by sequencing had all received d4T before switching to TDF. 2013 Antiviral therapy Result HIV K65R 27 31 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. This was especially notable for patients with the K65R mutation; the HIV RNA IQR was 3.2-3.7 log10 c/mL when this mutation was present compared to 3.1-3.9 log10 c/mL when the M184V mutation was present and 3.2-4.5log10 c/mL when major NNRTI mutations were present. 2013 Antiviral therapy Result HIV K65R;M184V 50;175 54;180 NNRTI 235 240 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. We evaluated for associations between the presence of the K65R, M184V, or major NNRTI mutations as identified through consensus sequencing. 2013 Antiviral therapy Result HIV K65R;M184V 58;64 62;69 NNRTI 80 85 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. A similar pattern was observed when measuring fold-change (FC) increase in the IC50, with I408T showing 4-FC, L317W 1.52-FC, and V169M, 1.23-FC increase. 2013 AIDS research and therapy Result HIV I408T;L317W;V169M 90;110;129 95;115;134 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. After 16 passages, 2 new mutations materialized: I408T in V4 and P849Q in gp41 (Table 1). 2013 AIDS research and therapy Result HIV I408T;P849Q 49;65 54;70 gp41 74 78 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. After 16 passages, the mutation I840Y arose in gp41. 2013 AIDS research and therapy Result HIV I840Y 32 37 gp41 47 51 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. After 4 passages of CC1/85 virus in the presence of sub-inhibitory MVC concentrations, some mutations, such as V169M and N192K in V2, L317W in V3, I408A in V4, D462N, N463T, S464T and N465aD in V5, and L820I, I829V and Y837C in gp41,were associated with increased p24 levels (Table 1). 2013 AIDS research and therapy Result HIV D462N;I408A;I829V;L317W;L820I;N192K;N463T;S464T;V169M;Y837C 160;147;209;134;202;121;167;174;111;219 165;152;214;139;207;126;172;179;116;224 gp41;p24 228;264 232;267 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. For VCV, 2 mutations emerged after 4 passages: V169M in V2 and L317W in V3. 2013 AIDS research and therapy Result HIV L317W;V169M 63;47 68;52 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. For VCV, I408T increased the IC50 by 2-FC, and the mutants I408T, L317W/I408T and V169M/L317W/I408T showed MPI of 94%, 93% and 94%, respectively (Table 3 and Figure 1B). 2013 AIDS research and therapy Result HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W 94;88;82;9;59;72;66 99;93;87;14;64;77;71 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Infectivity percentage was 75% for V169M, 76% for L317W, 80% for I408T, 76% for the double mutants V169M/L317W, 63% for V169M/I408T, 67% for L317W/I408T, and 67% for the triple mutant V169M/L317W/I408T (Figure 2). 2013 AIDS research and therapy Result HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W;L317W;L317W;V169M;V169M;V169M 196;190;184;65;126;147;50;105;141;35;99;120 201;195;189;70;131;152;55;110;146;40;104;125 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. It is noteworthy that the mutation I408A in V4 appeared after 4 passages and disappeared at passage 16, when a new mutation, I408T, surfaced at the same position. 2013 AIDS research and therapy Result HIV I408A;I408T 35;125 40;130 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. L317W and V169M/L317W mutants presented intermediate resistance of 95% and 94%, respectively. 2013 AIDS research and therapy Result HIV L317W;V169M;L317W 16;10;0 21;15;5 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. No significant MPI diminution occurred for the single mutant V169M (96%). 2013 AIDS research and therapy Result HIV V169M 61 66 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Significant (85%) reduction in MVC's MPI was apparent for I408T, 84% for the double mutant V169M/I408T, 85% for L317W/I408T, and 83% for the triple mutant V169M/L317W/I408T. 2013 AIDS research and therapy Result HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W;V169M 167;161;155;58;97;118;112;91 172;166;160;63;102;123;117;96 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. The double mutants V169M/L317W exhibited 1.30-FC, V169M/I408T 4-FC and L317W/I408T 3-FC, and 3.31-FC was evident for the triple mutant V169M/L317W/I408T (Table 2 and Figure 1A). 2013 AIDS research and therapy Result HIV I408T;L317W;V169M;I408T;I408T;L317W;L317W;V169M;V169M 147;141;135;56;77;25;71;19;50 152;146;140;61;82;30;76;24;55 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. The single mutants V169M and L317W and the double mutants V169M/L317W and V169M/I408T retained their susceptibility to VCV, reaching 100% inhibition in some cases. 2013 AIDS research and therapy Result HIV I408T;L317W;L317W;V169M;V169M;V169M 80;29;64;19;58;74 85;34;69;24;63;79 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. 2LTR products peaked at 12 hours post-infection for WT, Q137R and D202G viruses (Figure 3G). 2013 Retrovirology Result HIV D202G;Q137R 66;56 71;61 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. A previously characterized IN mutant, H12Y, was used as a control in all the subsequent experiments (the H12 residue is not surface accessible). 2013 Retrovirology Result HIV H12Y 38 42 IN 27 29 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. All IID-IN mutants bound to GST-SAP18 at levels comparable to WT, except for Q137R which exhibited ~4-fold decrease in SAP18 binding (Figure 7B and C). 2013 Retrovirology Result HIV Q137R 77 82 IN 8 10 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. All IID-IN mutants exhibited WT patterns of viral protein levels and processing in producer cells, except for H12Y (Figure 4A and B), which exhibited the presence of an additional alpha-p24 antibody-reactive band that migrated between 26 and 37 kDa (Figure 4A). 2013 Retrovirology Result HIV H12Y 110 114 p24;IN 186;8 189;10 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Among the partially defective mutants, the K71R mutant exhibited an intermediate phenotype, in that it was ~2.5 fold defective for early RT (Figure 3C), and ~3.5 fold defective for late RT (Figure 3F). 2013 Retrovirology Result HIV K71R 43 47 RT;RT 137;186 139;188 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Among these mutations the previously published INI1-interaction defective mutant, K71R, that retains 40% binding to INI1, was also identified (see Table 1,). 2013 Retrovirology Result HIV K71R 82 86 IN;IN;IN;IN 47;116;47;116 50;119;51;120 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Analysis of the 2LTR formation by all the mutants at the peak level (12 hrs.) as compared to WT indicated that Q137R, D202G and K111E exhibited partial reduction in 2LTR circle formation (Figure 3I). 2013 Retrovirology Result HIV D202G;K111E;Q137R 118;128;111 123;133;116 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Except for H12Y, there was no significant decrease in protein levels among IID-IN mutants compared to that of WT, indicating that the dramatic defect in early events is not due to defects in incorporation of IN and RT. 2013 Retrovirology Result HIV H12Y 11 15 IN;IN;RT 79;208;215 81;210;217 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. For all the above experiments of determining early and late RT and 2LTR circle formation, we used the Class I catalytic mutant, D116A, specifically defective for integration, as control. 2013 Retrovirology Result HIV D116A 128 133 RT 60 62 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Furthermore, these mutants could be categorized into two groups: (1) Mutants that were highly defective for INI1 binding, including H12Y (previously identified), Q137R, and D202G; and (2) mutants that displayed partial binding, including S147G and K71R (Figure 1C and D). 2013 Retrovirology Result HIV D202G;H12Y;K71R;Q137R;S147G 173;132;248;162;238 178;136;252;167;243 IN;IN 108;108 111;112 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. H12Y virions exhibited the presence of immature particles, which were very similar to that of DeltaIN virions (Figure 5A). 2013 Retrovirology Result HIV H12Y 0 4 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. H12Y, Q137R, and D202G, mutants that were highly defective for inducing GFP expression, exhibited background levels of p24 in the culture supernatants. 2013 Retrovirology Result HIV D202G;Q137R;H12Y 17;6;0 22;11;4 p24 119 122 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. However, in vitro binding of His6-K111E with GST-INI1 revealed ~60% binding compared to His6-WT (data not shown). 2013 Retrovirology Result HIV K111E 34 39 IN;IN 49;49 52;53 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. However, K71R and S147G mutants exhibited no significant defect in 2LTR formation (Figure 3I). 2013 Retrovirology Result HIV K71R;S147G 9;18 13;23 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. However, K71R mutant exhibited a partial defect in early RT and more significant defect in late RT (Figure 3B and 3E). 2013 Retrovirology Result HIV K71R 9 13 RT;RT 57;96 59;98 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. In case of D202G, about 25% of the particles exhibited acentric crescent shaped, or immature or aberrant cores (Figure 5B). 2013 Retrovirology Result HIV D202G 11 16 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. In contrast, H12Y, Q137R, and D202G mutants all showed severe defects in both early and late RT product formation compared to WT (Figure 3A and D). 2013 Retrovirology Result HIV D202G;H12Y;Q137R 30;13;19 35;17;24 RT 93 95 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. In summary, among the IID-IN mutants, Q137R showed defect in binding to SAP18, LEDGF, and RT but no defect in binding to GEMIN2. 2013 Retrovirology Result HIV Q137R 38 43 IN;RT 26;90 28;92 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Interestingly, the mutant D202G, one of the highly defective IID-IN mutants, exhibited significant binding to all tested host factors including SAP18, LEDGF and GEMIN2, as well as to RT, indicating that the strongest defect observed for this mutant correlated with its defect in binding specifically to INI1. 2013 Retrovirology Result HIV D202G 26 31 IN;IN;IN;RT 303;65;303;183 306;67;307;185 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. K111E failed to express high enough protein levels in mammalian cells to be tested for INI1 binding in this system. 2013 Retrovirology Result HIV K111E 0 5 IN;IN 87;87 90;91 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. K71R, S147G and K111E mutants that exhibited a partial defect in inducing GFP expression, demonstrated a partial defect in p24 production. 2013 Retrovirology Result HIV K111E;S147G;K71R 16;6;0 21;11;4 p24 123 126 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Of the partially defective mutants, K71R appeared to be the most defective in multi-round replication, however, the p24 levels of this mutant also rose during the infection time course and reached levels above background. 2013 Retrovirology Result HIV K71R 36 40 p24 116 119 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Our analysis of the peak cultures (after 16 days) from one of the partially defective mutants, S147G, indicated that the IN mutation in these virions had been reverted to wild type (data not shown). 2013 Retrovirology Result HIV S147G 95 100 IN 121 123 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Our results indicated that while Q137R displayed ~45% RT binding, D202G bound RT at levels close to WT (~80% binding compared to WT) (Figure 7H and I). 2013 Retrovirology Result HIV D202G;Q137R 66;33 71;38 RT;RT 54;78 56;80 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Q137R mutant virions harbored crescent and acentric capsids that were stuck to the viral envelope (Figure 5A and B). 2013 Retrovirology Result HIV Q137R 0 5 Env;Capsid 89;52 97;59 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Since highly defective mutants, Q137R and D202G were defective for in vivo reverse transcription, these mutants were also tested for their ability to bind GST-RT-p51 and GST-RT-p66. 2013 Retrovirology Result HIV D202G;Q137R 42;32 47;37 RT;RT;RT 75;159;174 96;161;176 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The defect was most dramatic for H12Y, which had no detectable levels of 2LTR circles (Figure 3G and I). 2013 Retrovirology Result HIV H12Y 33 37 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The H12Y mutant showed decreased levels of incorporation of IN and displayed higher levels of unprocessed Gag proteins within the virions including Pr55 and Pr41 (Figure 4C). 2013 Retrovirology Result HIV H12Y 4 8 Gag;IN;PR;PR 106;60;148;157 109;62;150;159 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The mutant D202G, although demonstrated presence of mature particles, exhibited the presence of significant acentric crescent like particles (Figure 5B). 2013 Retrovirology Result HIV D202G 11 16 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The partially defective IID mutants (K111E and S147G) exhibited normal capsid morphology very similar to that of the wild type (Figure 5A). 2013 Retrovirology Result HIV K111E;S147G 37;47 43;52 Capsid 71 77 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The partially defective IID-IN mutants, K71R, S147G, and K111E were also tested for early or late RT product formation. 2013 Retrovirology Result HIV K111E;K71R;S147G 57;40;46 62;44;51 IN;RT 28;98 30;100 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The partially defective mutants S147G and K111E were not defective for early (Figure 3B) or late RT (Figure 3E). 2013 Retrovirology Result HIV K111E;S147G 42;32 47;37 RT 97 99 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The remaining two mutants, S147G and K111E, did not exhibit significant defects in early or late RT (Figure 3C, 3F). 2013 Retrovirology Result HIV K111E;S147G 37;27 42;32 RT 97 99 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. The two mutants Q137R and D202G were severely impaired for integration; the remaining mutants K71R, S147G and K111E exhibited partial defect in integration that was correlated to their impairment in binding to INI1. 2013 Retrovirology Result HIV D202G;K111E;K71R;Q137R;S147G 26;110;94;16;100 31;115;98;21;105 IN;IN 210;210 213;214 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. These results indicated that while H12Y mutant exhibits a slightly defective processing, the remaining IID-IN mutants undergo normal protein processing in producer cells. 2013 Retrovirology Result HIV H12Y 35 39 IN 107 109 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Viruses harboring H12Y, Q137R, and D202G, IID-IN mutations that were severely impaired for INI1 binding were highly defective for replication as very little GFP expression above basal levels was observed at peak points in these cultures (Figure 2A). 2013 Retrovirology Result HIV D202G;H12Y;Q137R 35;18;24 40;22;29 IN;IN;IN 91;46;91 94;48;95 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. We were able to purify S147G and K111E and found that they retained their ability to carry out in vitro strand transfer activities, indicating that the catalytic activity of these mutants was unaffected (data not shown). 2013 Retrovirology Result HIV K111E;S147G 33;23 38;28 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. While the replication of mutants K71R, S147G, and K111E, which bore partial binding to INI1, peaked at 14 days, the overall GFP levels were lower than that of cells infected with WT virus, indicating a partial defect in replication of these viruses. 2013 Retrovirology Result HIV K111E;K71R;S147G 50;33;39 55;37;44 IN;IN 87;87 90;91 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. At physiological dNTP concentrations (1-25 muM) we observed a 1.5-fold decrease in the translocation efficiency of K65R compared to WT RT under these conditions. 2013 Retrovirology Result HIV K65R 115 119 RT 135 137 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Data in Additional file 1: Figure S1 show that WT RT binds EFdA-MP-terminated T/P only slightly stronger than K65R RT (~1.3-fold). 2013 Retrovirology Result HIV K65R 110 114 RT;RT 50;115 52;117 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Figure 1 and Table 2 show that RT mutation K65R causes hypersusceptibility to EFdA-TP. 2013 Retrovirology Result HIV K65R 43 47 RT 31 33 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Figure 2 shows that EFdA-TP blocked translocation and acted as a strong TDRTI against both WT and K65R RTs. 2013 Retrovirology Result HIV K65R 98 102 RT 103 106 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Hence, another possible mechanism by which the K65R mutation could enhance susceptibility to EFdA is by further suppressing translocation of RT on the EFdA-MP-terminated T/P. 2013 Retrovirology Result HIV K65R 47 51 RT 141 143 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. In contrast, there was a 3-fold resistance to tenofovir caused by K65R RT mutation. 2013 Retrovirology Result HIV K65R 66 70 RT 71 73 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. In the presence of ATP the K65R mutation caused a 2.5-fold increase in susceptibility to EFdA-TP (Table 2). 2013 Retrovirology Result HIV K65R 27 31 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Our results showed that under these conditions the ratio of the incorporation efficiency (kcat/Km) of EFdA-TP and the incorporation efficiency of dATP by K65R RT was between 0.8 and 1. 2013 Retrovirology Result HIV K65R 154 158 RT 159 161 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Table 1 shows that K65R-containing viruses are at least 2.5-fold more susceptible to EFdA than WT viruses. 2013 Retrovirology Result HIV K65R 19 23 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The above experiments provide strong evidence that K65R mutation confers hypersusceptibility to EFdA mainly through decreased excision. 2013 Retrovirology Result HIV K65R 51 55 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The first hypothesis was that the K65R RT mutation selectively enhances incorporation of the EFdA-TP inhibitor into DNA because of changes in kinetic parameters such as binding or turnover rate of inhibitor incorporation. 2013 Retrovirology Result HIV K65R 34 38 RT 39 41 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The K65R mutation enhances susceptibility of RT to EFdA-TP. 2013 Retrovirology Result HIV K65R 4 8 RT 45 47 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The K65R RT mutation does not enhance susceptibility to EFdA by significantly affecting enzyme translocation on EFdA-MP-terminated template/primers. 2013 Retrovirology Result HIV K65R 4 8 RT 9 11 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The K65R RT mutation does not enhance susceptibility to EFdA by significantly affecting incorporation of the inhibitor. 2013 Retrovirology Result HIV K65R 4 8 RT 9 11 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The K65R RT mutation enhances susceptibility of HIV to EFdA. 2013 Retrovirology Result HIV K65R 4 8 RT 9 11 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Therefore, in the following experiments we examined whether the K65R substitution could enhance susceptibility to EFdA by suppressing the ability of RT to unblock EFdA-MP-terminated primers. 2013 Retrovirology Result HIV K65R 64 68 RT 149 151 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Therefore, the small differences in the selectivity, translocation activity, and DNA binding of WT and K65R RTs were not sufficient to explain the hypersusceptibility we observed in cell-based and RT assays with EFdA and EFdA-TP respectively. 2013 Retrovirology Result HIV K65R 103 107 RT;RT 108;197 111;199 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. These results suggest that the K65R mutation does not have a significant effect on the binding and incorporation of EFdA-TP (Table 4). 2013 Retrovirology Result HIV K65R 31 35 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. To determine the biochemical mechanism of increased K65R HIV inhibition by EFdA we examined several possible mechanisms. 2013 Retrovirology Result HIV K65R 52 56 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. To determine whether the lower amount of observed translocated K65R RT T/PEFdA-MP complex (Figure 2) is due to a decreased affinity of K65R RT for EFdA-MP-terminated T/P we studied the effect of K65R on the formation of RT T/PEFdA-MP binary complex using gel-shift assays. 2013 Retrovirology Result HIV K65R;K65R;K65R 63;135;195 67;139;199 RT;RT;RT 68;140;220 70;142;222 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. To evaluate this hypothesis we used the site-specific Fe2+ foot-printing assay to assess the translocation state of WT and K65R RT T/PEFdA-MP complexes in the absence, and in the presence of varying concentrations of the next incoming dNTP. 2013 Retrovirology Result HIV K65R 123 127 RT 128 130 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Using ATP as the pyrophosphate donor, we found that the initial rates of the rescue reactions were 2.8-fold slower by K65R than by WT RT (Figure 3A). 2013 Retrovirology Result HIV K65R 118 122 RT 134 136 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We used a primer extension assay to compare the effect of EFdA-TP on DNA-dependent DNA polymerization by WT and K65R RTs. 2013 Retrovirology Result HIV K65R 112 116 RT 117 120 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We used as a positive control of resistance to K65R HIV-1 the nucleotide analog TDF. 2013 Retrovirology Result HIV K65R 47 51 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. Both wild type and E478Q RTs were sensitive to efavirenz in a concentration dependent manner (Figure 1b and 1d). 2013 Biochemistry Result HIV E478Q 19 24 RT 25 28 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. E478Q is an RNase H negative mutant with functional polymerase activity . 2013 Biochemistry Result HIV E478Q 0 5 Pol 52 62 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. However, we observed that the E478Q showed a much greater sensitivity to efavirenz inhibition and was completely inhibited at 2.5 muM (Figure 1c and 1d). 2013 Biochemistry Result HIV E478Q 30 35 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. RNase H negative mutant E478Q RT is more sensitive to efavirenz than wild type. 2013 Biochemistry Result HIV E478Q 24 29 RT 30 32 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. The greater drug sensitivity of E478Q RT implies that a functional RNase H active site helps to counteract the inhibitory properties of efavirenz. 2013 Biochemistry Result HIV E478Q 32 37 RT 38 40 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. The mutant D10 (K101E+G190S+M41L+T215Y) was isolated from a patient who had failed efavirenz treatment . 2013 Biochemistry Result HIV G190S;K101E;M41L;T215Y 22;16;28;33 27;21;32;38 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. We titrated efavirenz into polymerization assays with either wild type or E478Q RT. 2013 Biochemistry Result HIV E478Q 74 79 RT 80 82 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. Higher frequencies of K70R (p = 0.016) and M46I (p = 0.026) were present among patients with recent HIV-1 infection; there were no statistically significant differences in the frequencies of other RAMs. 2013 PloS one Result HIV K70R;M46I 22;43 26;47 HIV infections 100 115 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. In patients with chronic HIV-1 infection, T215D/E/F/I/S/Y (0.8%), Y181C (0.5%), and M46I (0.4%) were the most common RAMs to the corresponding drug classes. 2013 PloS one Result HIV M46I;T215D;T215E;T215F;T215I;T215S;T215Y;Y181C 84;42;42;42;42;42;42;66 88;57;57;57;57;57;57;71 HIV infections 17 40 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. In patients with recent HIV-1 infection, M184I/V and T215D/E/F/I/S/Y were the most common RAMs to NRTIs (1.1% each); Y181C was the most common RAM to NNRTIs (1.3%), and M46I was the most common RAM to PIs (1.5%). 2013 PloS one Result HIV M184I;M184V;M46I;T215D;T215E;T215F;T215I;T215S;T215Y;Y181C 41;41;169;53;53;53;53;53;53;117 48;48;173;68;68;68;68;68;68;122 NNRTI;NRTI;PI 150;98;201 156;103;204 HIV infections 24 39 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. A quintuple mutant, Q67H/K70R/H87P/T107N/L111I, designated 5Mut and recently described as having a hyperstable capsid , showed stable vRNA for up to 75 minutes post-infection (Figure 6A). 2013 Retrovirology Result HIV H87P;K70R;L111I;Q67H;T107N 30;25;41;20;35 34;29;46;24;40 Capsid 111 117 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Because of the unexpected rapid RNA staining of E45A HIV-1, we hypothesized that the integrity of E45A capsid is compromised by the mutation, allowing molecules, such as antibodies and the fluorescent dye, to enter the core more rapidly. 2013 Retrovirology Result HIV E45A;E45A 48;98 52;102 Capsid 103 109 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. By contrast, the level of reverse transcripts for the K203A and 5Mut viruses did not increase over the 155-minute time course. 2013 Retrovirology Result HIV K203A 54 59 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. CA E45A HIV-1 cores are more permeable than WT HIV-1 cores. 2013 Retrovirology Result HIV E45A 3 7 Capsid 0 2 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. However, unlike the K203A mutant, E45A HIV-1 had an increase in vRNA staining between 15 - 25 minutes post-infection, followed by a significant decline at 35 minutes post-infection (Figure 6A). 2013 Retrovirology Result HIV E45A;K203A 34;20 38;25 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. However, we observed both viral-associated RNA and NC staining in E45A virions, suggesting that both the small molecule dye and the anti-NC antibodies could penetrate the cores. 2013 Retrovirology Result HIV E45A 66 70 NC;NC 51;137 53;139 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. In addition, EU-labeled E45A HIV-1 particles containing MS2-GFP were stained and showed higher levels of staining compared to WT MS2-GFP particles (Figure 7C). 2013 Retrovirology Result HIV E45A 24 28 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. In contrast, E45A HIV-1 has detectable infectivity (20-30-fold lower than WT HIV-1) , perhaps allowing more efficient initiation of reverse transcription to occur if the core partially uncoated or opened earlier. 2013 Retrovirology Result HIV E45A 13 17 RT 132 153 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Indeed, we observed a more rapid accumulation of early reverse transcripts for E45A HIV-1 as compared to WT HIV-1, K203A HIV-1, or 5Mut HIV-1. 2013 Retrovirology Result HIV E45A;K203A 79;115 83;120 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Interestingly, E45A HIV-1, which had previously been described as having a hyperstable capsid and lower infectivity as compared to WT HIV-1 , exhibited a rapid vRNA decay profile that was similar to that of K203A. 2013 Retrovirology Result HIV E45A;K203A 15;207 19;212 Capsid 87 93 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. K203A vRNA staining began to decay after 25 minutes post-infection instead of after 55 minutes post-infection observed for WT HIV-1. 2013 Retrovirology Result HIV K203A 0 5 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Moreover, K203A HIV-1 did not show the usual transient increase in vRNA staining typically observed for wild type HIV-1, suggesting that CA core opening for this mutant occurred within 15 - 25 minutes post-infection. 2013 Retrovirology Result HIV K203A 10 15 Capsid 137 139 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The CA K203A mutant was previously shown to have highly unstable cores and low infectivity . 2013 Retrovirology Result HIV K203A 7 12 Capsid 4 6 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The co-localization of NC and viral-associated RNA in E45A cores was approximately 65%, whereas it was only approximately 10% for WT cores (Figure 7B). 2013 Retrovirology Result HIV E45A 54 58 NC 23 25 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The E45A phenotype was partially reversed with the addition of the mutation of R132T, resulting in a double mutant for which EU staining resembled WT HIV-1. 2013 Retrovirology Result HIV E45A;R132T 4;79 8;84 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The E45A/R132T mutant is more infectious than the E45A mutant, indicating that the functional defect induced by E45A is partially rescued by R132T . 2013 Retrovirology Result HIV E45A;E45A;E45A;R132T;R132T 4;50;112;9;141 8;54;116;14;146 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The level of E45A reverse transcripts was 2-fold higher than the WT vDNA level at 15 minutes post-infection that continued to increase above WT HIV-1 reverse transcripts during the time course. 2013 Retrovirology Result HIV E45A 13 17 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The results for early reverse transcripts for the K203A mutant were consistent with previous reports looking at significantly later time points , which may be due to a completely unstable core that leads to poor infectivity for this virus . 2013 Retrovirology Result HIV K203A 50 55 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The vRNA staining assay revealed that D443N HIV-1 had a similar decay curve as WT HIV-1 in TZM-bl cells (Figure 5C), indicating that vRNA degradation was not due to viral RNase H activity. 2013 Retrovirology Result HIV D443N 38 43 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. These data indicate that the capsid of E45A HIV-1 dissociated early after infection. 2013 Retrovirology Result HIV E45A 39 43 Capsid 29 35 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. To determine whether E45A cores allow entry of different molecules into the core more easily than WT CA cores, equal amounts of EU-labeled WT HIV-1 and E45A HIV-1 particles in buffer (2.5 ng CA) were fixed onto slides and stained for EU by the small dye and for NC by monoclonal antibodies (Figure 7A). 2013 Retrovirology Result HIV E45A;E45A 21;152 25;156 NC;Capsid;Capsid 262;101;191 264;103;193 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. To test this, we made EU-labeled HIV-1 containing the D443N amino acid substitution in RT. 2013 Retrovirology Result HIV D443N 54 59 RT 87 89 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Whereas WT vRNA staining began to decay after 45 minutes post-infection in untreated cells, PF74 led to lower vRNA staining at the first time point, showing no transient increase in vRNA staining that is observed with most viruses in cells without the CA inhibitor, similar to the unstable K203A mutant. 2013 Retrovirology Result HIV K203A 290 295 Capsid 252 254 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. Effect of maraviroc on recombinant virus containing F312W/T314A/E317D in the V3 loop. 2013 PloS one Result HIV E317D;F312W;T314A 64;52;58 69;57;63 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. Finally, we examined the effects of T199K on the replication of recombinant viruses carrying four mutations in the V3 loop. 2013 PloS one Result HIV T199K 36 41 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. HIV-1V3-M5 containing the five mutations I304V/F312W/T314A/E317D/I318V in the V3 loop with a JR-FL background (Figure 1A) exhibits noncompetitive resistance to maraviroc. 2013 PloS one Result HIV E317D;F312W;I304V;I318V;T314A 59;47;41;65;53 64;52;46;70;58 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. HIV-1V3-M5 replication can be enhanced by T199K in V3 mutants to a level comparable with that in HIV-1JR-FL . 2013 PloS one Result HIV T199K 42 47 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. However HIV-1234 containing F312W/T314A/E317D could replicate in the presence of 1 microM maraviroc, although p24 Gag production was 1.8% of that in its absence. 2013 PloS one Result HIV E317D;F312W;T314A 40;28;34 45;33;39 p24;Gag 110;114 113;117 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. I304V, F312W, T314A, E317D, and I318V were the polymorphic mutations detected in R5 clinical isolates. 2013 PloS one Result HIV E317D;F312W;I318V;T314A;I304V 21;7;32;14;0 26;12;37;19;5 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. In the presence of maraviroc, HIV-11234 produced 6.7% of p24 Gag of that in its absence (Figure 3); however, HIV-11234/T199K replication increased up to 43% (Figure 5). 2013 PloS one Result HIV T199K 119 124 p24;Gag 57;61 60;64 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. Of note, HIV-11245 replication was completely suppressed by 1 microM maraviroc (Figure 3); however, HIV-11245/T199K could replicate in the presence of 1 microM maraviroc, although the p24 production was only 2% of that in the absence maraviroc (Figure 5). 2013 PloS one Result HIV T199K 110 115 p24 184 187 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. p24 Gag production by HIV-1V3-M5/T199K increased from 3100 pg/ml to 10,500 pg/ml in the presence of 1 microM maraviroc, whereas there was no significant increase in its absence. 2013 PloS one Result HIV T199K 33 38 p24;Gag 0;4 3;7 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. Similarly, HIV-1234/T199K replication was significantly enhanced from 31 pg/ml to 650 pg/ml in the presence of 1 microM maraviroc but not in its absence. 2013 PloS one Result HIV T199K 20 25 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. These results indicated that the absence of T314A in the triplet could be compensated by I304V, I318V, or T199K and result in noncompetitive resistance. 2013 PloS one Result HIV I304V;I318V;T199K;T314A 89;96;106;44 94;101;111;49 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. These results indicated that triplet mutations in the V3 loop are crucial for noncompetitive resistance, and I304V, I318V, or T199K can increase viral fitness. 2013 PloS one Result HIV I304V;I318V;T199K 109;116;126 114;121;131 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. These two viruses contained three common mutations: F312W, T314A, and E317D. 2013 PloS one Result HIV E317D;F312W;T314A 70;52;59 75;57;64 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. Thus, none of these viruses exhibited defective growth, although F312W caused a moderate decrease in p24 Gag production in the absence of maraviroc. 2013 PloS one Result HIV F312W 65 70 p24;Gag 101;105 104;108 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. To address structural impacts of the V3 maraviroc-resistance mutations, we performed MD simulations of the HIV-1JR-FL gp120 outer domain V3 loop with and without the five mutations of HIV-1V3-M5 (I304V/F312W/T314A/E317D/I318V). 2013 PloS one Result HIV E317D;F312W;I304V;I318V;T314A 214;202;196;220;208 219;207;201;225;213 gp120 118 123 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. We further examined whether HIV-1234 containing the triplet mutation F312W/T314A/E317D exhibited noncompetitive resistance (Figure 4). 2013 PloS one Result HIV E317D;F312W;T314A 81;69;75 86;74;80 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. (ii) K65N, which occurred in one patient receiving TDF; (iii) T69D, V75M, and V75T, which occurred in 1.3%, 2.5%, and 0.3% respectively; (iv) T215I occurred in 1.4% of patients; and (v) K219R and K219N, occurred in 1.6% and 0.9% respectively. 2013 PloS one Result HIV K219N;K219R;K65N;T215I;T69D;V75M;V75T 196;184;3;140;60;68;78 201;191;9;147;66;72;82 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. A higher proportion of patients receiving EFV (37% of 801) had viruses with V106M compared with those receiving NVP (12% of 86; p<0.001). 2013 PloS one Result HIV V106M 76 81 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. A higher proportion of patients receiving NVP (41% of 86) had viruses with Y181C compared with those receiving EFV (5% of 801; p<0.001). 2013 PloS one Result HIV Y181C 75 80 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Additional NNRTI-resistance mutations not shown in Table 4 included (i) A98G, which occurred in 3.3% of NNRTI-treated patients; (ii) V106A, which occurred in 0.6% of NNRTI-treated patients; (iii) E138G/Q, which occurred in 0.9% and 0.9% of patients, respectively; (iv) V179D/E/T/F, which occurred in 8.5%, 0.7%, 0.5%, and 0% of NNRTI-treated patients respectively; (v) Y181I/V, which occurred in one and no patient, respectively; (vi) H221Y, which occurred in 5.9% of EFV-treated and 9.3% of NVP-treated patients (p<0.001); (vii) P225H, which occurred in 13.6% of EFV-treated and 5.8% of NVP-treated patients (p = 0.01); and (viii) F227C, which occurred in three patients; and (ix) K238T, which occurred in 2.3% of NNRTI-treated patients. 2013 PloS one Result HIV A98G;E138G;E138Q;F227C;H221Y;K238T;P225H;V106A;V179D;V179E;V179F;V179T;Y181I;Y181V 70;194;194;630;433;680;528;131;267;267;267;267;367;367 76;203;203;637;440;687;535;138;280;280;280;280;376;376 NNRTI;NNRTI;NNRTI;NNRTI;NNRTI 11;104;166;328;715 16;109;171;333;720 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Additional NRTI resistance mutations not shown in Table 3 included (i) A62V, which occurred more commonly in patients receiving TDF (19/153; 12.4%) than in those receiving AZT, d4T, or ABC (36/774, 4.7%; p<0.001); and among TDF-recipients, A62V occurred more commonly in samples with K65R plus M184V (14/39, 35.9%) than in samples with M184V alone (4/50, 8%; p<0.001), K65R alone (1/31, 3.2%; p<0.001), or neither K65R nor M184V (0/33, 0%; p<0.001). 2013 PloS one Result HIV A62V;A62V;K65R;K65R;K65R;M184V;M184V;M184V 69;240;284;369;414;294;336;423 75;244;288;373;418;299;341;428 NRTI 11 15 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Among the patients receiving EFV, L100I occurred in a higher proportion of the 53 patients receiving ABC/3TC (23%) compared with the remaining 748 patients (3.1%; p<0.001) and Y181C occurred in a higher proportion of the 127 patients receiving TDF/3TC (18%) compared with the remaining 674 patients (2.5%; p<0.001). 2013 PloS one Result HIV L100I;Y181C 34;176 39;181 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. In 19 of 21 patients, Y188C occurred in combination with V106M. 2013 PloS one Result HIV V106M;Y188C 57;22 62;27 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. K65R occurred in 70/153 (45.8%) patients failing ARV and receiving TDF and in 9/54 (16.7%) patients receiving ABC compared with 20/720 (2.8%) patients receiving d4T or AZT (p<0.001 for both TDF and ABC). 2013 PloS one Result HIV K65R 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. K65R occurred in a higher proportion of patients receiving TDF plus 3TC plus NVP than TDF plus 3TC plus EFV (16/20; 80% vs. 2013 PloS one Result HIV K65R 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. K70EG occurred in a higher proportion of patients receiving TDF compared to patients receiving d4T or AZT. 2013 PloS one Result HIV K70E;K70G 0;0 5;5 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. K70QEG occurred in 12/153 (7.8%) patients receiving TDF compared with 3/720(0.4%) receiving d4T or AZT (p<0.001). 2013 PloS one Result HIV K70E;K70G;K70Q 0;0;0 6;6;6 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L74VI occurred in 13/153 (8.5%) patients receiving TDF and 30/54 (55.6%) receiving ABC compared with 1.8% receiving d4T or AZT (p<0.001 for both TDF and ABC). 2013 PloS one Result HIV L74I;L74V 0;0 5;5 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Of note, 18 of the 20 patients with this mutation also had K65R. 2013 PloS one Result HIV K65R 59 63 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. S68N occurred in 1.4% (20) of patients, a proportion higher than the 0.1% and 0.3% previously found in the subtype C and non-subtype C RTI-experienced patients in HIVDB. 2013 PloS one Result HIV S68N 0 4 RT 135 138 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. T165L, a nonpolymorphic mutation previously reported to be associated with NRTI therapy occurred in 1.6% (22) of patients, a proportion similar to the 1.3% found in the ~3,600 RTI-experienced subtype C-infected patients in HIVDB but significantly higher than the 0.4% found in the ~25,000 RTI-experienced non-subtype C-infected patients in HIVDB. 2013 PloS one Result HIV T165L 0 5 NRTI;RT;RT 75;176;289 79;179;292 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Three mutations - K65R, L74VI, and Y115F - occurred in a higher proportion of patients receiving TDF and ABC compared to patients receiving d4T or AZT. 2013 PloS one Result HIV K65R;L74I;L74V;Y115F 18;24;24;35 22;29;29;40 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Y115F occurred in 16/153 (10.5%) patients receiving TDF and 16/54 (29.6%) receiving ABC compared with 4/720 (0.6%) patients receiving d4T or AZT (p<0.001; for both TDF and ABC). 2013 PloS one Result HIV Y115F 0 5 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Y188C, a mutation previously reported in 0.1% of non-subtype C sequences occurred in 1.5% (21) patients in this study. 2013 PloS one Result HIV Y188C 0 5 23840857 Functional complementation of a model target to study Vpu sensitivity. The D84K mutation, conferring a receptor binding defect (BD) on the Env and the L493V mutation, conferring a fusion defect (FD) on the Env are able to functionally complement one another. 2013 PloS one Result HIV D84K;L493V 4;80 8;85 Env;Env 68;135 71;138 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Clearly N276D mutation produced high-level resistance specifically to HJ16 in all three isolates (Table 4). 2013 PloS one Result HIV N276D 8 13 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. In order to ascertain that this rare mutation was indeed responsible for resistance to HJ16, N276D site-directed mutants were generated in the envs of three sensitive strains from different subtypes, selected from Table 1: the original VI1090 (CRF02_AG), 92RW009.6 (subtype A) and VI829 (subtype C). 2013 PloS one Result HIV N276D 93 98 Env 143 147 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Next, the impact of N276D on the sensitivity to HJ16 and other CD4bs mAbs (b12, VRC01 and VRC03), two llama single heavy chain antibodies or VHHs (A12 and 1B5); the CD4 "miniprotein" M48-U1 and soluble CD4 was assessed in the TZMbl neutralization assay. 2013 PloS one Result HIV N276D 20 25 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Remarkably the mutation, N276D conferred a 3 to 13 fold increase of sensitivity to both VRC01 and VRC03. 2013 PloS one Result HIV N276D 25 30 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Resistance Induction in VI1090 with HJ16 Results in a Unique N276D Mutation. 2013 PloS one Result HIV N276D 61 66 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Searching the Los Alamos database indicated that this N276D point mutation is only seen in 0.85% (19/2247) of group M isolates. 2013 PloS one Result HIV N276D 54 59 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Sequencing revealed the presence of a single point mutation in all four HJ16 resistant variants whereby the neutral asparagine (N) was replaced by the negatively charged aspartic acid (D) at position 276 (numbering according to HxB2), resulting in the loss of a potential N linked glycosylation site (PNGS). 2013 PloS one Result HIV D276D 167 206 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. The N276D Mutations Confers Selective Resistance to HJ16 across Subtypes. 2013 PloS one Result HIV N276D 4 9 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. There was no evidence of cross-resistance of the N276D mutants to other entry inhibitors used, as the difference in IC50 of mutant/WT was always less than twofold. 2013 PloS one Result HIV N276D 49 54 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. Analysis of RT mutations for 2005 demonstrated that the highest degree of expression was for M184V (41.3%), K103N (25.3%), and D67N (20.5%). 2010 Boletin de la Asociacion Medica de Puerto Rico Result HIV D67N;K103N;M184V 127;108;93 131;113;98 RT 12 14 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. As shown in Table III, the PI resistance-associated specific mutations with the highest degree of expression for 2005 were L63P (73.6%), M36I (26.2%), and L90M (21.0%). 2010 Boletin de la Asociacion Medica de Puerto Rico Result HIV L63P;L90M;M36I 123;155;137 127;159;141 PI 27 29 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. For women, N88D was among the top ten mutations (11.7%) while in males its expression was 9.3%. 2010 Boletin de la Asociacion Medica de Puerto Rico Result HIV N88D 11 15 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. For women, P225H was among the top ten mutations (6.6%) while in males its expression was 1.9%. 2010 Boletin de la Asociacion Medica de Puerto Rico Result HIV P225H 11 16 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. Significant differences between men and women for the expression of K103N (P=0.0456) and P225H (P=0.006) were recorded. 2010 Boletin de la Asociacion Medica de Puerto Rico Result HIV K103N;P225H 68;89 73;94 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. There was a significant difference between men and woman for L90M (P= 0.0337) and M46I (P= 0.0424), two major mutations associated with resistance to PI inhibitors. 2010 Boletin de la Asociacion Medica de Puerto Rico Result HIV L90M;M46I 61;82 65;86 PI 150 152 23904291 Persistence of HIV-1 transmitted drug resistance mutations. As expected, M184V was lost rapidly at a rate of 71 (95% CI, 34-149) per 100 PYFU. 2013 The Journal of infectious diseases Result HIV M184V 13 18 23904291 Persistence of HIV-1 transmitted drug resistance mutations. L90M was the most common PI mutation, with a rate of loss of 12 (95% CI, 5-31) mutations per 100 PYFU. 2013 The Journal of infectious diseases Result HIV L90M 0 4 PI 25 27 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M41L was commonly observed and highly persistent (rate of loss 8 (95% CI, 4-15) per 100 PYFU), and a similar low rate of loss was seen for other TAMs (D67N, L210W, and K219Q/N); however, K70R appeared to be lost more quickly. 2013 The Journal of infectious diseases Result HIV D67N;K219N;K219Q;K70R;L210W;M41L 151;168;168;187;157;0 155;175;175;191;162;4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. NNRTI mutations appeared to be lost more quickly than most TAMs (M41L, D67N, L210W, and K219Q/N) and the 215 revertants (P < .001 for both comparisons). 2013 The Journal of infectious diseases Result HIV D67N;K219N;K219Q;L210W;M41L 71;88;88;77;65 75;95;95;82;69 NNRTI 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Sensitivity analyses removing patients with M184V (n = 34), those with non-B subtype (n = 42), or patients with CD4 < 200 cells/mm3 at the first resistance test (n = 29) resulted in slightly lower absolute rates of TDR mutation loss but did not materially affect comparisons within and between drug classes. 2013 The Journal of infectious diseases Result HIV M184V 44 49 23904291 Persistence of HIV-1 transmitted drug resistance mutations. There was also a rapid transition of T215F and T215Y to one of the T215 revertants, but the revertants themselves were highly stable with a rate of loss of 5 (95% CI, 3-11) mutations per 100 PYFU. 2013 The Journal of infectious diseases Result HIV T215F;T215Y 37;47 42;52 23904291 Persistence of HIV-1 transmitted drug resistance mutations. There was no statistically significant difference in the rate of loss of NNRTI mutations (heterogeneity P = .1); K103N was the most common NNRTI mutation, with a rate of loss of 18 (95% CI, 10-34) mutations per 100 PYFU. 2013 The Journal of infectious diseases Result HIV K103N 113 118 NNRTI;NNRTI 73;139 78;144 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Although the K103N mutation was not present in any of 9 SGA and 12 end-point PCR-amplified plasma sequences at 3rd trimester of gestation, one out of eight pol sequences derived from maternal plasma collected after delivery (approximately one day after sdNVP) had the K103N mutation (clone pE7). 2013 Retrovirology Result HIV K103N;K103N 13;268 18;273 Pol 156 159 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Finally, the complete replacement of wild-type virus with NNRTI-resistant mutants was evident by 12 weeks postpartum coupled with a significant reduction of viral load in plasma and breast milk (Table 1); K103N mutation was present in 5 out of 8 (63%) pol sequences, whereas NNRTI resistance mutations V106M, Y188C or G190A were each present in 3 other sequences (Figure 3). 2013 Retrovirology Result HIV G190A;K103N;V106M;Y188C 318;205;302;309 323;210;307;314 NNRTI;NNRTI;Pol 58;275;252 63;280;255 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Four weeks after delivery, wild-type NVP-R susceptible virus was nearly replaced with variants carrying individual non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistance mutations such as K103N, V106M, Y188L and G190A, and importantly, the generation of a major clonally-amplified variant carrying K103N mutation in the mammary gland compartment (Figure 3). 2013 Retrovirology Result HIV G190A;K103N;K103N;V106M;Y188L 223;199;309;206;213 228;204;314;211;218 NNRTI;NNRTI 115;163 151;168 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Indeed, K103N mutation is one of the most common mutations selected by NVP as reported in previous MTCT studies. 2013 Retrovirology Result HIV K103N 8 13 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Moreover, in vitro studies indicated that K103N mutation has no effect on replication fitness, while the Y181C mutation results in a much less fit virus when introduced in the backbone of the subtype C molecular clone MJ4. 2013 Retrovirology Result HIV K103N;Y181C 42;105 47;110 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. The abundance of K103N clonal variants in the mother, and high-level viremia of the subtype C T/F K103N virus in the infant suggest that this mutation has little impact on viral fitness. 2013 Retrovirology Result HIV K103N;K103N 17;98 22;103 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. We observed that the K103N mutation which confers high-level resistance to NVP was present in all of the infant's pol gene sequences, and hence the T/F virus (marked with an arrow in Figure 2A), as well as in 50% of maternal plasma and 80% of breast milk pol sequences (Figure 3). 2013 Retrovirology Result HIV K103N 21 26 Pol;Pol 114;255 117;258 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Without exception, pol sequences from the major clonally-amplified virus population in both blood (2 out of 2) and mammary (6 out of 6) compartments had the K103N mutation (Figures 2B and 3). 2013 Retrovirology Result HIV K103N 157 162 Pol 19 22 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. As shown in Table 4, the most prevalent drug-resistance mutation among the 31 cases was M184V (n = 12, 38.7%), followed by K103N (n = 9, 29.0%), and T215Y/F (n = 6, 19.4%). 2013 PloS one Result HIV K103N;M184V;T215F;T215Y 123;88;149;149 128;93;156;156 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. However, M184V mutation was detected in 37.5% (3/8) of patients with 6.1-12.0 months of ART, and the prevalence increased to 80.0% (4/5) at 36.1 months of ART (red bars in. 2013 PloS one Result HIV M184V 9 14 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. However, polymorphisms at NNRTI-resistance mutation loci, V90I, E138A, and V106I, were found in 6 cases (10.2% in Table 4). 2013 PloS one Result HIV E138A;V106I;V90I 64;75;58 69;80;62 NNRTI 26 31 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. Importantly, among the 10 ART-naive children, a 1.5-year-old case had K103N and G190S NNRTI-resistance mutations (Table 5), suggesting the importance of HIV-1 drug-resistance testing in infants. 2013 PloS one Result HIV G190S;K103N 80;70 85;75 NNRTI 86 91 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. In the case of NVP and EFV resistance, K103N, V106A, V108I, Y181C/L, G190A, P225H, and M230L mutations were detected in more than half of patients after 6.0 months of ART (blue bars in. 2013 PloS one Result HIV G190A;K103N;M230L;P225H;V106A;V108I;Y181C;Y181L 69;39;87;76;46;53;60;60 74;44;92;81;51;58;67;67 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. In this case, both 3TC-resistance (M184V) and EFV-resistance (V108I and G190S) mutations were detected (Table 5). 2013 PloS one Result HIV G190S;M184V;V108I 72;35;62 77;40;68 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. This case possessed HIV-1 RT mutations M41L, V90I, A98G, M184V and T215Y, and the major NFV-resistance mutation L90M in PR. 2013 PloS one Result HIV A98G;L90M;M184V;M41L;T215Y;V90I 51;112;57;39;67;45 55;116;62;43;72;49 PR;RT 120;26 122;28 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. Additionally, VRC03 was uniquely sensitive to P470T. 2013 PloS one Result HIV P470T 46 51 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. D197N) would render JR-FL more resistant to 1F7 neutralization. 2013 PloS one Result HIV D197N 0 5 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. In contrast, 1F7 binding to the D368R mutant was completely ablated, even at the highest concentration tested (50 microg/mL). 2013 PloS one Result HIV D368R 32 37 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. Indeed, the JR-FL D197N mutant was ~8-fold more resistant to 1F7 and b12, and two-fold more resistant to VRC01 compared to wildtype JR-FL (Figure 7). 2013 PloS one Result HIV D197N 18 23 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. MAb 1F7 had a similar profile to that of b12 in being affected only by D368R (Figure 10A and B), whereas mAb VRC01 and its somatic variant VRC03 were sensitive to mutation R469S of gp120 in the C5 region (Figure 10A and B). 2013 PloS one Result HIV D368R;R469S 71;172 76;177 gp120 181 186 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. Notably, although K207A, N262A, and P470T were previously shown to ablate sCD4 binding to monomeric JR-CSF gp120, they had little or no effect on sCD4 binding to JR-FL native trimers (Figure 10A). 2013 PloS one Result HIV K207A;N262A;P470T 18;25;36 23;30;41 gp120 107 112 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. Of 13 JR-CSF PNGS mutants, three (N156Q, N197Q, and N301Q) were extremely sensitive to 1F7 (Figure 7). 2013 PloS one Result HIV N156Q;N197Q;N301Q 34;41;52 39;46;57 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. Only the D368R mutant knocked out binding of all the neutralizing ligands in our panel, including 1F7. 2013 PloS one Result HIV D368R 9 14 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. Overall, more mutants affected recognition of Env trimers by sCD4 than was the case with any of the mAbs (namely mutants T257Y, D368R, I371A, W427A, D457E, and R469S). 2013 PloS one Result HIV D368R;D457E;I371A;R469S;T257Y;W427A 128;149;135;160;121;142 133;154;140;165;126;147 Env 46 49 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. Overall, the BN-PAGE results confirm that 1F7 binds to a D368R-sensitive epitope overlapping the CD4bs on trimeric Env, and that, with this mutant Env trimer panel at least, 1F7 has a binding profile that is more akin to that of b12 than the other CD4bs mAbs tested here. 2013 PloS one Result HIV D368R 57 62 Env;Env 115;147 118;150 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. The sensitivity of JR-CSF to 1F7 conferred by the N197Q glycan knockout mutation (Figure 7) opens up the possibility that adding a glycan at the unoccupied site. 2013 PloS one Result HIV N197Q 50 55 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. The typically non-neutralizing CD4bs mAb b6 also neutralized two of these variants (N197Q and N301Q), albeit less potently than 1F7. 2013 PloS one Result HIV N197Q;N301Q 84;94 90;99 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. This was most notable for N262A and P470T, and suggests a more "relaxed" quaternary structure that grants access to a CD4bs mAb that cannot otherwise recognize parental Env trimers. 2013 PloS one Result HIV N262A;P470T 26;36 31;41 Env 169 172 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. To quantify the effect of D368R mutation, we titrated mAb 1F7 against parent JR-FL and D368R mutant trimers (Figure 10C). 2013 PloS one Result HIV D368R;D368R 26;87 31;92 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. We next tested whether the potent neutralization of 1F7 against the JR-CSF mutants N197Q, N156Q, and N301Q corresponded to a change in 1F7 binding to either soluble Env derived from virus lysates or to cell surface-expressed Env. 2013 PloS one Result HIV N156Q;N197Q;N301Q 90;83;101 95;88;106 Env;Env 165;225 168;228 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. Sequences from 5 patients were identified with drug resistance-associated mutations, giving a prevalence of 3.6% (5/139) HIVDR, among which 3 resistance mutations to protease inhibitors (M46I, G73A, L90LM); 2 to nucleoside reverse transcriptase inhibitors (M184V), T215F); and 3 to non-nucleoside reverse transcriptase inhibitors (K103N, Y181C, Y181YC, M230ML). 2013 PloS one Result HIV G73A;K103N;L90L;L90M;M184V;M230L;M230M;M46I;T215F;Y181C;Y181C;Y181Y 193;331;199;199;257;353;353;187;265;345;338;345 197;336;204;204;262;359;359;191;270;351;343;351 NNRTI;NRTI;PR 282;212;166 318;244;174 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. Specifically, the most frequent mutations were M184V/I (4/4) conferring high level resistance to 2 NRTIs (lamivudine and emtricitabine), K103K/N (3/4) conferring high level resistance 2 NNRTIs (nevirapine and efavirenz), while only one mutation to thymidine analogs (mainly zidovudine and stavudine) was identified. 2013 PloS one Result HIV K103K;K103N;M184I;M184V 137;137;47;47 144;144;54;54 NNRTI;NRTI 186;99 192;104 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. As for the most prevalent mutations associated with NNRTI, the frequencies of K103N and V106A were approximately 20% (19.2% and 22.1%, respectively). 2013 PloS one Result HIV K103N;V106A 78;88 83;93 NNRTI 52 57 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. M184V/I was the most prevalent mutation associated with resistance to NRTI, with a frequency of 28.2%. 2013 PloS one Result HIV M184I;M184V 0;0 7;7 NRTI 70 74 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. One individual that was infected through homosexual contact, exhibited a high level of resistance to nelfinavir with ritonavir (NFV/r) with a D30N mutation and conferred intermediate resistance to all nucleoside reverse transcriptase inhibitors (NRTIs) with T69ins. 2013 PloS one Result HIV D30N;T69ins 142;258 146;264 NRTI;NRTI 201;246 233;251 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. The frequencies of some mutations, including A71TV, T69S, and V179D were relatively high between the therapy-naive and the ART-failure individuals but the impact on susceptibility to antiviral drugs was low; therefore, these mutations were not described in detail in this study. 2013 PloS one Result HIV A71T;A71V;T69S;V179D 45;45;52;62 50;50;56;67 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. The other individual infected through heterosexual contact, had mutations of L90M and A71V and exhibited low-level resistance to atazanavir with ritonavir (ATV/r) and fosamprenavir with ritonavir (FPV/r), intermediate resistance to indinavir with ritonavir (IDV/r) and saquinavir with ritonavir (SQV/r), and high resistance to NFV/r. 2013 PloS one Result HIV A71V;L90M 86;77 90;81 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. With the widespread use of AZT and d4T, the resistance mutations associated with these drugs, including K70R, T215F/Y and K219Q/E, were 4.5%, 6.8%, and 5.1%, respectively. 2013 PloS one Result HIV K219E;K219Q;K70R;T215F;T215Y 122;122;104;110;110 129;129;108;117;117 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. A second five sequence set was constructed, each with sequences that contain one of the L90M correlated mutations, which were labeled the inclusion sets. 2013 PloS one Result HIV L90M 88 92 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. A significantly higher predicted proteasomal cleavage score for PR 92 was obtained by the Q92K substitution (0.549), but this score is very close to the threshold of 0.500 and could very well be a false positive. 2013 PloS one Result HIV Q92K 90 94 PR 64 66 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. A total of five linear models constructed that predict L90M frequencies, each tailored for a specific correlated mutation (please refer to the methods section). 2013 PloS one Result HIV L90M 55 59 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. After HLA assignment, the frequency of L90M for each HLA assigned sequence set was measured. 2013 PloS one Result HIV L90M 39 43 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Although very indirect, this method could at least plausibly indicate lower frequencies of RT M184V in the presence of HLA*A*02. 2013 PloS one Result HIV M184V 94 99 RT 91 93 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. An additional mutation, Q92R was observed in the sequences. 2013 PloS one Result HIV Q92R 24 28 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. An important PR mutation observed in HIV sequences from drug exposed individuals, is L90M. 2013 PloS one Result HIV L90M 85 89 PR 13 15 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. At each step, resampling of was performed on both the inclusion set and the clean slates and the frequency of all the mutations, including L90M, were recorded. 2013 PloS one Result HIV L90M 139 143 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Because M184V is a reverse transcriptase inhibitor resistance mutation, only sequence with the common RTI mutation, L210W, were used in calculation to avoid bias sequences devoid of RT inhibitor resistance mutations. 2013 PloS one Result HIV L210W;M184V 116;8 121;13 RT;RT;RT 19;102;182 40;105;184 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Both the Q92K/R mutations did not have a profound negative impact on HLA binding affinity and did not change the rank percentage from the NetCTLPan results. 2013 PloS one Result HIV Q92K;Q92R 9;9 15;15 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. By referring to the HIVdb (http://hivdb.stanford.edu,), additional terms for the linear model were chosen based on observed PI resistance mutation patterns that occur in conjunction with the mutation and L90M. 2013 PloS one Result HIV L90M 204 208 PI 124 126 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Comparing viral loads in patients expressing the PR L90M mutation with those that do not, an increased viral load of (Mann-Whitney, , VC = Viral copies) was calculated. 2013 PloS one Result HIV L90M 52 56 PR 49 51 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Factors that may influence the frequency of L90M are not necessarily limited to the presence of HLA subtypes B*15 or B*48. 2013 PloS one Result HIV L90M 44 48 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Finally, HLA associated enriched within the PR region proximal to L90M and potential immunological escape inferred for the proposed novel epitopes. 2013 PloS one Result HIV L90M 66 70 PR 44 46 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Five sequence sets were constructed, each devoid of M46I, I54V, V71A, V82A and I84V respectively, which were referred to as clean slate sets. 2013 PloS one Result HIV I54V;I84V;M46I;V71A;V82A 58;79;52;64;70 62;83;56;68;74 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. For instance, if the patients from the sequence B*48+ or B*15+ underwent a treatment plan that prefers Tipranavir (TPV) or Duranavir (DRV), lower frequencies could also be observed, since L90M does not factor in during development of resistance to these drugs. 2013 PloS one Result HIV L90M 188 192 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. For instance, instead of measuring the singular effect of M46I frequency on L90M frequency, I84V was included as a second parameter in accordance with the relatively common M46I-I84V-L90M mutation pattern in PR sequences conferring high level resistance to nelfinavir (NFV), saquinavir (SQV), indinavir (IDV) and atazanavir (ATV). 2013 PloS one Result HIV I84V;I84V;L90M;L90M;M46I;M46I 92;178;76;183;58;173 96;182;80;187;62;177 PR 208 210 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. From HLA assignment data, the frequency of occurrence of L90M were measured. 2013 PloS one Result HIV L90M 57 61 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. From this data, a linear model was constructed to predict expected frequencies of L90M in a sequence set by using the frequencies of L90M correlated mutations as input parameters. 2013 PloS one Result HIV L90M;L90M 82;133 86;137 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. HLA subtypes other than HLA-B*15 and HLA-B*48 do not show significant negative correlation with L90M. 2013 PloS one Result HIV L90M 96 100 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. However, as shown in Table 6, I93L has a significant impact on proteasomal cleavage prediction score for position 93 in PR. 2013 PloS one Result HIV I93L 30 34 PR 120 122 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. However, due to the lower observed frequency of other PI resistance related mutations, it was further investigated whether the lower frequencies of L90M were truly due to the assigned HLA subtypes or due to a lack of acquired drug resistance. 2013 PloS one Result HIV L90M 148 152 PI 54 56 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. However, the co-occurrence of Q92K and I93L is severely diminished in HIV PR sequences . 2013 PloS one Result HIV I93L;Q92K 39;30 43;34 PR 74 76 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. In conjunction with I93L, the proteasomal score was further increased to 0.735. 2013 PloS one Result HIV I93L 20 24 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. In this section, the importance of L90M will be demonstrated by measuring its effect on viral load in patients undergoing antiretroviral therapy. 2013 PloS one Result HIV L90M 35 39 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Indeed, it is shown that the CTL escape provided by the PR I93L has higher avidity in terms of ELISPOT analysis. 2013 PloS one Result HIV I93L 59 63 PR 56 58 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Instead of using a single parameter in each model to predict the frequency of L90M, each model was constructed using the frequencies of multiple L90M-correlated mutations. 2013 PloS one Result HIV L90M;L90M 78;145 82;149 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. It is thought that selection against L90M mutation in HIV treated patients could have a positive effect on treatment outcome. 2013 PloS one Result HIV L90M 37 41 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. It was concluded that RT K43E could have caused false assignment of HLA subtype C*03 in Pol sequences obtained from drug exposed patients exhibiting other RT inhibitor resistance related mutations. 2013 PloS one Result HIV K43E 25 29 Pol;RT;RT 88;22;155 91;24;157 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. It was first assessed what substitutions are enriched in PR and RT in the absence of L90M. 2013 PloS one Result HIV L90M 85 89 PR;RT 57;64 59;66 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. It was relevant to this study to determine the influence of other HLA allotypes on L90M selection. 2013 PloS one Result HIV L90M 83 87 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. It was tested whether lower frequencies of L90M could be observed in PR sequences obtained from patients that are positive specific HLA subtypes. 2013 PloS one Result HIV L90M 43 47 PR 69 71 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Lower frequencies of L90M are observed in sequences with assigned HLA subtypes A*32, B*48 and B*15. 2013 PloS one Result HIV L90M 21 25 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Measurement of the impact of M46I, I54V, V71A, V82A, I84V frequencies on the frequency of L90M, was accomplished by the construction of a linear model. 2013 PloS one Result HIV I54V;I84V;L90M;M46I;V71A;V82A 35;53;90;29;41;47 39;57;94;33;45;51 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Mutations PR Q92K and Q92R are enriched in B*15+ and B*48+ sets. 2013 PloS one Result HIV Q92K;Q92R 13;22 17;26 PR 10 12 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Next, it was discovered that certain HLA subtypes associated mutations were enriched in sequence sets from drug exposed individuals that are devoid of L90M. 2013 PloS one Result HIV L90M 151 155 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. No significant diminished co-occurrence of Q92R and I93L was observed. 2013 PloS one Result HIV I93L;Q92R 52;43 56;47 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. None of the tested HLA subtypes showed negative association with L90M, even after adjusting L90M frequencies with the linear models mentioned earlier. 2013 PloS one Result HIV L90M;L90M 65;92 69;96 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Observation of the protease L90M substitution frequencies in sequences annotated with patient HLA data. 2013 PloS one Result HIV L90M 28 32 PR 19 27 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. One mutation, PR I93L, is known to facilitate resistance to the HLA-B*15 restricted epitope spanning PR 90-99, TQIGCTLNF (T9F). 2013 PloS one Result HIV I93L;T9F 17;122 21;125 PR;PR 14;101 16;103 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Only two allotypes were associated with diminished levels of L90M in PR, namely subtypes A*02 and B*15. 2013 PloS one Result HIV L90M 61 65 PR 69 71 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Paradoxically, subtype C*03, which shows strong linkage disequilibrium with subtype B*15, was positively associated with L90M. 2013 PloS one Result HIV L90M 121 125 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Referring back to Table 2, two substitutions, RT:Q207R (, direct) and RT:R211G (, indirect) associated with HLA-B*15 were enriched. 2013 PloS one Result HIV Q207R;R211G 49;73 54;78 RT;RT 46;70 48;72 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Regions spanning L90M were submitted to NetMHCPan for affinity analysis to HLA allotypes belonging to the HLA B*15, B*48 and A*32 subtypes. 2013 PloS one Result HIV L90M 17 21 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. RT substitution K43E. 2013 PloS one Result HIV K43E 16 20 RT 0 2 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. RT:R211G is also associated with A*32. 2013 PloS one Result HIV R211G 3 8 RT 0 2 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Sequence sets were divided based on the presence or absence of the mutation M184V, much like The sequence sets were divided based on the presence or absence of the M184V mutation. 2013 PloS one Result HIV M184V;M184V 76;164 81;169 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Significantly lower frequencies not only included L90M, but also major resistance mutations that tend to occur with PR 90 M. 2013 PloS one Result HIV L90M 50 54 PR 116 118 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The assignment of HLA A*02 did not yield a significantly negative correlation with L90M result, despite L90M enhancing the PR 76-84 HLA-A*02 restricted epitope. 2013 PloS one Result HIV L90M;L90M 83;104 87;108 PR 123 125 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The C-terminal of the M10F peptide is already at a known cleavage site overlapping with T9F. 2013 PloS one Result HIV M10F;T9F 22;88 26;91 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The E203D is flagged as NONADAPTED for the HLA*A*02 subtype and it can be assumed that lower occurrence of RT E203D is positively correlated with the presence of HLA*A*02. 2013 PloS one Result HIV E203D;E203D 4;110 9;115 RT 107 109 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The effect of L90M also has a positive effect on viral load. 2013 PloS one Result HIV L90M 14 18 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The frequencies commonly occurring PR mutations, M46I, I54V, A71V, V82A and I84V were also tested in both B*48 and B*15 subtype sequence sets. 2013 PloS one Result HIV A71V;I54V;I84V;M46I;V82A 61;55;76;49;67 65;59;80;53;71 PR 35 37 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The importance of L90M as a PI resistance mutation. 2013 PloS one Result HIV L90M 18 22 PI 28 30 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The influence of antiretroviral choice was explored to determine if bias was introduced resulting in lower observed frequency of L90M. 2013 PloS one Result HIV L90M 129 133 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The L90M protease mutation increases predicted binding affinity of peptides to HLA allotypes belonging to subtypes A*32, B*15 and B*48. 2013 PloS one Result HIV L90M 4 8 PR 9 17 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The L90M substitution is predicted to have a significant positive effect on HLA binding for the HLA-B*15 (B*1503), HLA A*32 (A*3201) and HLA-B*48 (B*4802) subtypes, with only a marginal increase in predicted binding affinity for HLA-A*0201. 2013 PloS one Result HIV L90M 4 8 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The mechanism behind the CTL immunity escape of T9F provided by the PR I93L mutation is unknown. 2013 PloS one Result HIV I93L;T9F 71;48 75;51 PR 68 70 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The mutation causes an increase in immunogenicity of an A*02 epitope spanning RT 181-189, YQYMDDLYV (Y9V). 2013 PloS one Result HIV Y9V 101 104 RT 78 80 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The mutation Q92K is also associated with HLA escape referenced from the table used earlier. 2013 PloS one Result HIV Q92K 13 17 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The mutation Q92R was found in addition to be enriched in both B*15+ and B*48+ sequence sets. 2013 PloS one Result HIV Q92R 13 17 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The mutations RT:K102R and RT:K103R associated with HLA:B*48 mutation also occur at higher frequencies in the PR:90L set. 2013 PloS one Result HIV K102R;K103R 17;30 22;35 PR;RT;RT 110;14;27 112;16;29 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The observed frequency of L90M in the B*48+ and B*15+ and B*48+/B*15+ combined sets were compared with the expected L90M frequency produced by the models by using a Fisher's exact test. 2013 PloS one Result HIV L90M;L90M 26;116 30;120 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The observed lower frequencies of other PI resistance mutations do not account for the lower observed frequencies of L90M. 2013 PloS one Result HIV L90M 117 121 PI 40 42 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The peptide predicted to bind to subtype A*32, MTQIGCTLNF (M10F) was ranked among the 3%, providing weaker support of an HLA A*32 restricted epitope. 2013 PloS one Result HIV M10F 59 63 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The rationale behind this approach was to avoid under-fitting due to a lack of parameters, and importantly, ensuring the model captures the variance of L90M in a random set. 2013 PloS one Result HIV L90M 152 156 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The reason alternatives to RT (such as p17, p24, Int or Nef) were considered as sources of mutations to assign HLA allotypes, is due to the small amount of available HIV sequences that contain the PR L90M substitution in conjunction with p17, p24, Int or Nef sequences. 2013 PloS one Result HIV L90M 200 204 p24;p24;Nef;Nef;PR;RT 44;243;56;255;197;27 47;246;59;258;199;29 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The results in Table 3 demonstrate the significantly lower frequencies of L90M in sequences from patients with the assigned HLA-B*48 and HLA-B*15 subtypes. 2013 PloS one Result HIV L90M 74 78 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The results showed a decrease in the RT E203D mutation frequency (OR = 0.51, ) for the set that does not express the M184V mutation in RT. 2013 PloS one Result HIV E203D;M184V 40;117 45;122 RT;RT 37;135 39;137 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The robustness of the models are evident in that the expected L90M frequencies did not differ significantly for each tested mutation in all of the HLA subtype sets tested. 2013 PloS one Result HIV L90M 62 66 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The tests clearly show a significant difference in frequency of the observed frequencies of L90M versus the expected frequencies produced by all the linear models. 2013 PloS one Result HIV L90M 92 96 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. There was no evidence for enrichment of Q92K in the B*48+ sets. 2013 PloS one Result HIV Q92K 40 44 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. These results show that the lower observed frequencies of L90M in the B*15+ and B*48+ sets are not due to bias induced by antiretroviral choice. 2013 PloS one Result HIV L90M 58 62 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. These results were a good indication that subtypes B*48 and B*15 possibly drive selection against HIV-1 protease sequences with a L90M substitution. 2013 PloS one Result HIV L90M 130 134 PR 104 112 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. This is likely due the strong association of PR:90M with some substitutions that correlated with both drug resistance and HLA-B*15, namely PR:A71V and PR:L10I. 2013 PloS one Result HIV A71V;L10I 142;154 146;158 PR;PR;PR 45;139;151 47;141;153 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. To be thorough, A*02 was tested for negative correlation with an RT mutation that confers resistance against emtricitabine, abacavir and lamivudine, M184V. 2013 PloS one Result HIV M184V 149 154 RT 65 67 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. To find a possible causal relationship between the presence of HLA-B*48 or HLA-B*15 and the absence of L90M, IC50 values of peptides in the region 82-98 for representatives of various HLA subtypes were predicted with NetMHCPan. 2013 PloS one Result HIV L90M 103 107 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. To the author's knowledge, the peptides listed in Table 5 have not been shown to be epitopes anywhere in the literature, although L90M is known to enhance an HLA-A2 restricted epitope in the PR 76-84 region. 2013 PloS one Result HIV L90M 130 134 PR 191 193 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Using this methodology, Fisher exact tests on the occurrence of L90M in PR were performed between patient sequence sets that. 2013 PloS one Result HIV L90M 64 68 PR 72 74 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. With the additional substitutions included in HLA assignment, it was discovered that only subtypes A*32, B*15 and B*48 still showed significantly lower frequences of L90M. 2013 PloS one Result HIV L90M 166 170 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. With the sparsely available HLA annotation data, the frequency of L90M in patients with HLA annotations were compared. 2013 PloS one Result HIV L90M 66 70 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. A high HIV-1 RNA level was also significantly associated with Q151M (p<0.0001). 2013 PloS one Result HIV Q151M 62 67 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Finally, the Q151M and K65R mutations were positively associated to each other. 2013 PloS one Result HIV K65R;Q151M 23;13 27;18 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. In multivariate analysis, besides higher HIV-1 RNA VL level, probably associated with longer duration of failure, we found that d4T-use remained independently associated with the presence of MNR mutations (either Q151M or K65R). 2013 PloS one Result HIV K65R;Q151M 222;213 226;218 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. In multivariate analysis, independent risk factors for K65R were d4T-containing regimen (OR [95% CI]: 3.02 [1.12-8.13]), high HIV-RNA level (OR [95% CI]: 3.97 [1.64-9.61]) and duration >30 months under current first-line regimen (OR [95% CI]: 2.6 [1.16-5.83]) (table 1). 2013 PloS one Result HIV K65R 55 59 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. In multivariate analysis, independent risk factors for Q151M were d4T-containing regimen (Odds ratio (OR) [95% confidence interval (CI)]: 2.21 [1.05-4.65]), high HIV-1 RNA level (OR [95% CI]: 4.02 [2.13-7.59]), and duration >30 months under current first-line regimen (OR [95% CI]: 2.11 [1.18-3.76]) (table 1). 2013 PloS one Result HIV Q151M 55 60 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. In our study, other NRTI-RAMs known to be associated with Q151M-mediated multi-nucleoside resistance including A62V, V75I, F77L, and F116Y, were also significantly more common in patients harboring the Q151M mutation (p<0.001). 2013 PloS one Result HIV A62V;F116Y;F77L;Q151M;Q151M;V75I 111;133;123;58;202;117 115;138;127;63;207;121 NRTI 20 24 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. In univariate analysis, Q151M was significantly more frequent in patients on d4T-containing regimens (14.3%) than in those on AZT-containing regimens (6.3%) (p = 0.005). 2013 PloS one Result HIV Q151M 24 29 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Indeed, K65R was detected in 12/59 (20.3%) patients harboring Q151M compared to 3.9% of patients without Q151M (chi2 test, p<0.001). 2013 PloS one Result HIV K65R;Q151M;Q151M 8;62;105 12;67;110 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Q151M mutation tended to be associated with age <=15 years (p = 0.069) and duration >30 months under current regimen (p = 0.071). 2013 PloS one Result HIV Q151M 0 5 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Regarding MNR mutations, a total of 66 subjects (66/520, 12.7%) presented >=1 MNR mutation, including Q151M, K65R, and Insert69 for 59 (11.3%), 29 (5.6%), and 2 (0.4%) patients, respectively. 2013 PloS one Result HIV K65R;Q151M 109;102 113;107 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. The most frequently detected mutations were: M184I/V (92.3%), Y181C/I/V (47.1%), T215I/C/F/N/S (38.8%), D67E/G/N (37.3%), K103N/R/S (33.9%), and G190A/Q/S (32.5%). 2013 PloS one Result HIV D67E;D67G;D67N;G190A;G190Q;G190S;K103N;K103R;K103S;M184I;M184V;T215C;T215F;T215I;T215N;T215S;Y181C;Y181I;Y181V 104;104;104;145;145;145;122;122;122;45;45;81;81;81;81;81;62;62;62 112;112;112;154;154;154;131;131;131;52;52;94;94;94;94;94;71;71;71 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. The occurrence of K65R was significantly associated with d4T-containing regimens (p = 0.017) and high HIV-1 RNA level (p = 0.003), while there was a trend with duration >30 months under current first-line regimen (p = 0.054). 2013 PloS one Result HIV K65R 18 22 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. This might explain the presence of Q151M mutation among some patients under AZT regimen (6.3%) at the time of genotyping. 2013 PloS one Result HIV Q151M 35 40 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Thus, our data strongly suggests that d4T per se is directly associated with the occurrence of both Q151M and K65R mutations. 2013 PloS one Result HIV K65R;Q151M 110;100 114;105 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. To identify factors associated with the presence of Q151M and K65R mutations, univariate and multivariate logistic regression analysis were performed using the following variables: gender, age group (<= or >15 years), HIV-1 RNA VL level (<= or >4.5log10 copies/mL), current first-line regimen (d4T- or AZT-containing) and duration (<= or >30 months) at sampling time. 2013 PloS one Result HIV K65R;Q151M 62;52 66;57 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Consistent with particle analysis by EM (Figure 5), p24 content in core fractions 9-10 remained comparable between the WT virus produced in mock-treated cells (4.6% +-1.9% of total p24 content) and T174I virus produced in the presence of GS-B (4.6% +-1.0%), whereas that of WT virus produced in the presence of GS-B was 2-fold lower (2.3% +-0.6%) (Figure 6A). 2013 PloS one Result HIV T174I 198 203 p24;p24 52;181 55;184 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Consistent with the gradient distribution of p24, conical cores were abundant in samples from the mock-treated WT virus and GS-B-treated T174I mutant virus, but were significantly reduced in abundance, with greater shape variations, in samples from the GS-B-treated WT virus (Figure S1). 2013 PloS one Result HIV T174I 137 142 p24 45 48 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Importantly, no changes in the IN dimer content were detected in the NCINI-resistant T174I mutant virus produced in the presence of GS-B, a result consistent with the EM and core analysis data. 2013 PloS one Result HIV T174I 85 90 IN 31 33 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Importantly, the T174I-resistant mutant produced in the presence of NCINIs was refractory to the block in vDNA synthesis (Figure 4C), confirming that the induced RT defect is mediated through binding integrase. 2013 PloS one Result HIV T174I 17 22 IN;RT 200;162 209;164 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Importantly, the T174I-resistant virus was minimally affected by treatment with GS-B, and the phenotype distribution mimicked that of mock-treated wild-type (WT) virus (Figure 5C). 2013 PloS one Result HIV T174I 17 22 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. The T174I mutation in IN confers resistance to the NCINI class of inhibitors. 2013 PloS one Result HIV T174I 4 9 IN 22 24 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. The T174I virus is substantially less sensitive to the late-stage inhibition of both GS-A and GS-B, but retains full sensitivity to RAL and ATV (Figure 1A), confirming that the late-stage antiviral effect of NCINIs is still driven by targeting the viral IN protein. 2013 PloS one Result HIV T174I 4 9 IN 254 256 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. To further assess the observed morphological core defects induced by NCINIs, WT and T174I virus produced in the presence and absence of 1 microM GS-B were fractionated over a detergent-sucrose gradient using a previously described ultracentrifugation method. 2013 PloS one Result HIV T174I 84 89 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. Finally, two K103S drug-related mutations and one K103N polymorphism were all clustered in the A1 subtype. 2013 BMC infectious diseases Result HIV K103N;K103S 50;13 55;18 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. Interestingly, L89M protease polymorphism (potentially associated with resistance to fosamprenavir, and to a lesser extent to darunavir and lopinavir) was commonly detected with a 76.1% prevalence, equally distributed in all different non-B clades. 2013 BMC infectious diseases Result HIV L89M 15 19 PR 20 28 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. K103N and M41L mutations were on five lists and the K103S mutation was on four lists. 2013 BMC infectious diseases Result HIV K103S;M41L;K103N 52;10;0 57;14;5 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. K103S and M41L were found in two and one women, respectively, while M184V was not detected. 2013 BMC infectious diseases Result HIV M184V;M41L;K103S 68;10;0 73;14;5 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. (1) Mutations at or near sites of autoproteolysis acting in conjunction with other mutations in PR20 presumably increase the longevity of active PR20 in vivo by limiting degradation; (2) PR20 exhibits enhanced thermal stability relative to PR, which contributes to its functionality and viability of the virus (primarily through selection of mutations L33F and L63P) and (3) PR20 cleaves peptides corresponding to sites in the Gag polyprotein essential for viral maturation. 2013 Biochemistry Result HIV L33F;L63P 352;361 356;365 Gag;PR;PR;PR;PR;PR 427;96;145;187;240;375 430;98;147;189;242;377 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Another multi-drug resistant mutant, MDR769 (PDB accession code ITW7) which exhibits a pronounced "wide-open" conformation of both flaps, also contains several of the substitutions seen in PR20: namely, S37N, I62V, I63P, A71V, I84V, and L90M. 2013 Biochemistry Result HIV A71V;I62V;I63P;I84V;L90M;S37N 221;209;215;227;237;203 225;213;219;231;241;207 PR 189 191 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. As it was not possible even after repeated attempts to isolate full length active PRL33F/L63P, we introduced a conservative E34D substitution, which occurs rarely if at all at the P1' position of a variety of PR substrates and thus was thought unlikely to promote cleavage. 2013 Biochemistry Result HIV E34D;L63P 124;89 128;93 PR;PR 82;209 84;211 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Based on our earlier observation with PR that a single substitution mutation T26A dramatically shifts the monomer-dimer equilibrium towards the monomer (Kd >500 muM), we introduced the same mutation in PR20. 2013 Biochemistry Result HIV T26A 77 81 PR;PR 38;202 40;204 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. In the absence of inhibitors PRT26A/L33F//L63P exhibits a typically weak thermal transition, but surprisingly, with a Tm of ~68 C that is very similar to that of PR20T26A and 7-8 C higher than that of PRT26A (Figure 5D). 2013 Biochemistry Result HIV L33F;L63P 36;42 40;46 PR;PR 29;203 31;205 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Incubation of 13 muM PR (which also includes C67A and C95A substitutions, Figure 1B) for 23-70 h at room temperature in 50 mM sodium acetate buffer, pH 5, resulted in a small, time dependent appearance of products of autoproteolysis (Figure 2A, bands marked P). 2013 Biochemistry Result HIV C67A;C95A 45;54 49;58 PR 21 23 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Interestingly, A V mutation at P2 of the NC/SP2 site was shown to accompany the pair of PR mutations L33F/L63P in three HIV sequences derived from patients exhibiting multiple drug resistance. 2013 Biochemistry Result HIV L33F;L63P 101;106 105;110 SP2;NC;PR 44;41;88 47;43;90 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Mutations defined as major DRMs associated with DRV and saqunavir (SQV) resistance are 147V, I54L, I84V (DRV), and L90M (SQV). 2013 Biochemistry Result HIV I54L;I84V;L90M 93;99;115 97;103;119 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Natural mutations L33F and L63P in PR20 occur at positions that are mutated (L33I, L63I) from the wild type to limit autoproteolysis of PR, and the presence of L63P provided a reasonable hypothesis to account for diminished autoproteolytic activity, since Pro occurs very rarely at the P1 position of substrates cleaved by PR. 2013 Biochemistry Result HIV L33F;L33I;L63I;L63P;L63P 18;77;83;27;160 22;81;87;31;164 PR;PR;PR 35;136;323 37;138;325 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Notably biochemical and structural studies are unreliable to carry out without this substitution in the wild-type protease because of rapid autoproteloysis leading to dimer dissociation and loss of catalytic activity and the mutation Q7K is not expected to influence autoproteolysis at L33/E34 and L63/I64 sites, which is indeed our focus. 2013 Biochemistry Result HIV Q7K 234 237 PR 114 122 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Notably, thermal denaturation of PRL33F/E34D/L63P in the presence of a two-fold excess of DRV gives a biphasic transition curve that closely resembles that of PR with a large DeltaH and a Tm for the major transition that is only 2.7 C lower than that for PR/DRV, and 10 C higher than PR20/DRV complex (Figure 5E), indicative of tight binding to the inhibitor. 2013 Biochemistry Result HIV E34D;L33F;L63P 40;35;45 44;39;49 PR;PR;PR;PR 33;159;256;286 35;161;258;288 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Substitutions of two PR20 residues, L33F and L63P, in PR or its monomeric model, PRT26A, increase the monomer stability to an extent comparable with PR20, but permit effective DRV binding to a PR dimer. 2013 Biochemistry Result HIV L33F;L63P 36;45 40;49 PR;PR;PR;PR;PR 21;54;81;149;193 23;56;83;151;195 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Taken together the present observations suggest that L33F and L63P in the wild-type context contribute significantly to stabilize the momomer fold while retaining the very high affinity for DRV. 2013 Biochemistry Result HIV L33F;L63P 53;62 57;66 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. The DRM, ANAM-11, bears six mutations identical or similar to PR20 (L10I/F, M36I, L63P, A71V, I84V, L90M) and exhibits similar properties of increased dimer dissociation (Kd = 0.1 +- 0.04 muM) along with moderately enhanced thermal stability (Table 1A). 2013 Biochemistry Result HIV A71V;I84V;L10F;L10I;L63P;L90M;M36I 88;94;68;68;82;100;76 92;98;74;74;86;104;80 PR 62 64 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. The Tm of PRT26A/L33F/L63P, like that of PR20, is essentially unaffected in the presence of a 2-fold molar excess of DRV; however, DeltaH for this transition is increased by DRV, possibly due to weak interaction between the protease monomer and the inhibitor. 2013 Biochemistry Result HIV L33F;L63P 17;22 21;26 PR;PR;PR 224;10;41 232;12;43 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Thermal stability of PR20 and its monomeric T26A mutant. 2013 Biochemistry Result HIV T26A 44 48 PR 21 23 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. This modification resulted in barely visible accumulation of PRL33F/E34D/L63P, sufficient to purify and examine its thermal stability and inhibitor binding. 2013 Biochemistry Result HIV E34D;L33F;L63P 68;63;73 72;67;77 PR 61 63 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. Thus L33F and L63P are also unlikely to play a significant role in the >4000-fold diminished DRV binding affinity of PR20 relative to PR, and mutations at other sites must be involved in drug resistance. 2013 Biochemistry Result HIV L33F;L63P 5;14 9;18 PR;PR 117;134 119;136 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. To ascertain that Leu5/Trp6 site is not a preferred site for autoproteolysis, we created a revertant bearing K7Q mutation (wild-type site) in PR20. 2013 Biochemistry Result HIV K7Q 109 112 PR 142 144 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. To examine the effects of these mutations we introduced L33F and L63P into a PR background (termed PRL33F/L63P). 2013 Biochemistry Result HIV L33F;L63P;L63P 56;65;106 60;69;110 PR;PR 77;99 79;101 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. To overcome this problem a construct was designed bearing mutations Q7K, L331 and L63I at residues at or near the three major sites of autoproteolysis. 2013 Biochemistry Result HIV L63I;Q7K 82;68 86;71 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. We also examined monomeric PRT26A/L33F/L63P to assess the effect of L33F and L63P on thermal stability of the PRT26A monomer fold. 2013 Biochemistry Result HIV L33F;L63P;L33F;L63P 34;39;68;77 38;43;72;81 PR;PR 27;110 29;112 24079831 Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease. We chose to retain the Q7K mutation as all our previous studies were carried out with this mutation, thus enabling a strict comparison with our present PR20 data on its characterization. 2013 Biochemistry Result HIV Q7K 23 26 PR 152 154 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. Among the 12 patients with evidence of primary resistance based on the IAS list, 11 of them presented resistance mutations according to the WHO guidelines while patient ID#7 (Table 1) exhibited the mutations K101P that is not considered by the WHO guidelines. 2013 Journal of the International AIDS Society Result HIV K101P 208 213 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. The most prevalent resistance mutations associated with NNRTI were K103N and G190A. 2013 Journal of the International AIDS Society Result HIV G190A;K103N 77;67 82;72 NNRTI 56 61 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. K103N and Y181C were the most frequent NNRTI mutations in patients on EFV- and NVP-based regimens, respectively. 2013 BMC infectious diseases Result HIV Y181C;K103N 10;0 15;5 NNRTI 39 44 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. M184V and K103N were present in combination in 50% of the patients with DRMs. 2013 BMC infectious diseases Result HIV K103N;M184V 10;0 15;5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. Of the NNRTI-associated mutations, K103N (6 of 8, 75%) was the most frequent, followed by Y181C/H (3 of 8, 37.5%). 2013 BMC infectious diseases Result HIV K103N;Y181C;Y181H 35;90;90 40;97;97 NNRTI 7 12 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. Of the NRTI-associated DRMs, M184V was the most frequent (8 of 8, 100%). 2013 BMC infectious diseases Result HIV M184V 29 34 NRTI 7 11 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. Thymidine-associated mutations (TAMs) were rare with only one patient (1 of 8, 12.5%) harboring T215Y mutation in combination with M184V. 2013 BMC infectious diseases Result HIV M184V;T215Y 131;96 136;101 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. A Q148K IN-DNA model was built, but as it reveals no new information, the model is not shown. 2013 PloS one Result HIV Q148K 2 7 IN 8 10 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. A single conformation for the terminal 3' adenylate of the Q148H/G140S and N155H IN-DNA complexes was modeled with the nucleobase pi-stacked against DTG's metal-chelating scaffold (Figures 4A and 4B, respectively). 2013 PloS one Result HIV G140S;N155H;Q148H 65;75;59 70;80;64 IN;PI 81;130 83;132 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For instance, the distance between the Calpha atoms of D64 and N155H was increased by roughly 0.5 A compared with wild-type IN. 2013 PloS one Result HIV N155H 63 68 IN 124 126 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For N155H IN, the local structure of the alpha4 helix was distorted by the residue substitution, disrupting the H-bonds between the backbone CO of E152 and backbone NH of K156 and the backbone CO of S153 and backbone NH of E157 with distances of >=3.5 A between the heavy atoms. 2013 PloS one Result HIV N155H 4 9 IN 10 12 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For Q148H/G140S IN, the Q148H substitution perturbed the C-terminal end of the active-site loop displacing residues Y143 through G149 with the 310 helix pushed away from the DDE motif. 2013 PloS one Result HIV G140S;Q148H;Q148H 10;4;24 15;9;29 IN 16 18 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For Q148R IN, residue P145 was displaced up and away from the base of the catalytic pocket, affecting residues Y143, N144 and Q146, but without disrupting the 310 helix (comprised of residues N144-S147). 2013 PloS one Result HIV Q148R 4 9 IN 10 12 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. In constructing our Q148R IN model, we mutated residue Q148 of the HIV-1 IN model to Arg and then modified its rotameric state to match that of the corresponding residue from a selected Tn5 transposase template. 2013 PloS one Result HIV Q148R 20 25 IN;IN 26;73 28;75 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. It is difficult to discern the structural impact the G140S substitution may have on the active-site loop since Ser is the naturally occurring amino acid at PFV IN position 209, and a crystal structure of a S217Q/S209G PFV IN mutant is unavailable. 2013 PloS one Result HIV G140S;S209G;S217Q 53;212;206 58;217;211 IN;IN 160;222 162;224 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Nevertheless, the structural effects of the G140S substitution are likely to be considerable given the obvious and significant difference between Gly and Ser. 2013 PloS one Result HIV G140S 44 49 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Our Q148H/G140S and N155H IN models were built in a similar fashion using segments from the S217H and N224H PFV IN crystal structures, respectively, to capture the structural disturbances induced by the mutant residues. 2013 PloS one Result HIV G140S;N155H;N224H;Q148H;S217H 10;20;102;4;92 15;25;107;9;97 IN;IN 26;112 28;114 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Residue Q148H, however, underwent the largest shift in position as evidenced by the roughly 1.0 A displacement of its Calpha atom relative to that of the wild-type residue, weakening the H-bond between its backbone CO and backbone NH of E152. 2013 PloS one Result HIV Q148H 8 13 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The catalytic sites of the Q148R, Q148H/G140S and N155H IN-DNA models are illustrated in Figures 3, 4A and 4B, respectively. 2013 PloS one Result HIV G140S;N155H;Q148H;Q148R 40;50;34;27 45;55;39;32 IN 56 58 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The N155H substitution also caused the base of the catalytic pocket to widen. 2013 PloS one Result HIV N155H 4 9 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Q148H/G140S and N155H IN-DNA models have DTG docked into their active sites with poses set essentially identical to that of the IN-DNA-DTG model (Figure 2D). 2013 PloS one Result HIV G140S;N155H;Q148H 10;20;4 15;25;9 IN;IN 26;132 28;134 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Q148R IN-DNA model does not include an IN inhibitor in its active site so as to highlight the ionic interaction between the side chains of Q148R and E152. 2013 PloS one Result HIV Q148R;Q148R 4;143 9;148 IN;IN 10;43 12;45 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. While the placement of these adenines is fairly similar to that of the IN-DNA-DTG model, the adenine from the N155H IN-DNA model is actually shifted up by roughly 0.5 A and angled away from DTG's metal-chelating scaffold by almost 20 compared with the adenine from the IN-DNA-DTG model. 2013 PloS one Result HIV N155H 110 115 IN;IN;IN 71;116;270 73;118;272 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. However, when performing sensitivity analyses with a more strictly defined population who either had started their first ART or with a prior on-treatment GRT available(Table S1) those associations of adherence levels with emergence of new NNRTI or M184V mutations were no longer apparent, possibly owing to the lower sample size. 2013 PloS one Result HIV M184V 248 253 NNRTI 239 244 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. In multivariable models, adherence was still significantly associated with development of a new M184V mutation (8.38 [1.26-55.70], p=0.03), however the confidence intervals are very wide and reflected the small sample size of this subgroup. 2013 PloS one Result HIV M184V 96 101 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. In the group of NNRTI recipients there was a steady increase in the proportion of tests with resistance mutations for all three outcomes - the presence of any mutations, NNRTI mutations, or M184V mutation. 2013 PloS one Result HIV M184V 190 195 NNRTI;NNRTI 16;170 21;175 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. In univariable analyses, the only outcome showing a statistically significant association with adherence in the PI/r group was the emergence of the M184V mutation (n=137 patients on 3TC or FTC backbone, odds ratio [95% confidence interval]: 4.98 [1.41-17.62]) per increase in adherence stratum (Table 3). 2013 PloS one Result HIV M184V 148 153 PI 112 114 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. Increases in proportions of resistant viruses with lower adherence levels were observable when analysing any IAS-USA mutations or M184V as outcomes, but not with the emergence of PI mutations. 2013 PloS one Result HIV M184V 130 135 PI 179 181 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. The association between NNRTI mutations (1.46 [0.94-2.23]) and M184V (1.01 [0.49-2.08]) and adherence did not reach statistical significance. 2013 PloS one Result HIV M184V 63 68 NNRTI 24 29 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. This estimate should be interpreted with caution, however, because the M184V mutations did not occur in the middle adherence stratum. 2013 PloS one Result HIV M184V 71 76 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. Activities against variant strains of the virus, which contain the clinically important Y181C and K103N/Y181C mutations in the RT enzyme, were also determined. 2013 Journal of the American Chemical Society Result HIV K103N;Y181C;Y181C 98;88;104 103;93;109 RT 127 129 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. Among the new compounds the greatest potency towards the Y181C variant is for 10d and 10i at 170 and 160 nM. 2013 Journal of the American Chemical Society Result HIV Y181C 57 62 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. Crystal structures for additional complexes such as for 3 and 10b with Y181C, K103N, and K103N/Y181C HIV-RT are much desired to provide clarification. 2013 Journal of the American Chemical Society Result HIV K103N;K103N;Y181C;Y181C 78;89;71;95 83;94;76;100 RT 105 107 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. Furthermore, the usual pattern with NNRTIs is that they are more potent towards the single Y181C variant than the double K103N/Y181C variant. 2013 Journal of the American Chemical Society Result HIV K103N;Y181C;Y181C 121;91;127 126;96;132 NNRTI 36 42 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. However, the reason for the greater loss for 10b and 10h is unclear, and the reason for the gain in activity for adding the K103N mutation is especially obscure. 2013 Journal of the American Chemical Society Result HIV K103N 124 129 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. It is easy to say that the present compounds are expected to lose potency towards Y181C variants owing to loss of aryl-aryl contacts indicated in Figure 2 and in the crystal structures for the complexes of 3 and 4. 2013 Journal of the American Chemical Society Result HIV Y181C 82 87 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. It is unclear based on the present structures why conversion of Lys103 to Asn is beneficial for the heterobicyclic catechol diethers and not so for the cyanovinylphenyl analogs. 2013 Journal of the American Chemical Society Result HIV K103N 64 77 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. The K103N mutation is found in 57% of cases of NNRTI resistance and Y181C is found in 25% of cases. 2013 Journal of the American Chemical Society Result HIV K103N;Y181C 4;68 9;73 NNRTI 47 52 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. Thus, it was surprising to find that the new compounds are almost uniformly more active towards the K103N/Y181C than the Y181C variant. 2013 Journal of the American Chemical Society Result HIV K103N;Y181C;Y181C 100;106;121 105;111;126 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. Thus, the adverse effects of the Tyr181Cys mutation on potency for the indolizines can be attributed primarily to the loss of the aryl-aryl interaction between the bicyclic heterocycle and Tyr181. 2013 Journal of the American Chemical Society Result HIV Y181C 33 42 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. All differences in levels of CD4+ T cells between Naive mice and either LAI or LAINefP72A/P75A mice are statistically significant. 2013 Retrovirology Result HIV P75A 90 94 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Also, we expressed the mutated nef from LAINefP72A/P75A with the retroviral vector, LXSN, in CEM T cells and found it to be functional for CD4 downregulation but consistent with previous reports largely defective for MHCI downregulation (Figure 6D). 2013 Retrovirology Result HIV P72A;P75A 46;51 50;55 Nef 31 34 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. At week eight, however, nef sequence from one of the four mice infected with the P72A/P75A mutant virus had a clear shift from guanine to mostly cytosine at the first base of the codon for position 75 (Figure 9). 2013 Retrovirology Result HIV P72A;P75A 81;86 85;90 Nef 24 27 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. BLT mice were infected with 90,000 TCIU of LAINefP72A/P75A mutant virus (Figure 7). 2013 Retrovirology Result HIV P75A 54 58 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Even though the CD4+ T cells in LAINefP72A/P75A infected mice were nearly depleted, we continued monitoring the infection past eight weeks to determine if further mutations would occur during LAINefP72A/P75A infection. 2013 Retrovirology Result HIV P72A;P75A;P75A 198;43;203 202;47;207 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. In 293T cells, LAINefP72A/P75A expressed similar levels of Nef and p24gag compared to LAI (Figure 6A) and actively replicated in A3.01 T cells (Figure 6B). 2013 Retrovirology Result HIV P75A 26 30 Nef 59 62 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. In addition, the P72A/P75A Nef mutant and the wild type virus showed a similar time course for reduction of peripheral blood CD4+ T cells to 50% of total T cells in blood with LAINefP72A/P75A at 29.5 +- 4.1 dpi (n = 4) versus LAI at 21.6 +- 2.4 dpi (n = 7); p = 0.1554 (Figure 7B). 2013 Retrovirology Result HIV P72A;P72A;P75A;P75A 17;182;22;187 21;186;26;191 Nef 27 30 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. In contrast, comparisons between the levels of residual CD4+ T cells in mice infected with LAI versus LAINefP72A/P75A were not significantly different (Figure 8A). 2013 Retrovirology Result HIV P75A 113 117 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. In vivo selection pressure to correct the P72A/P75A mutation is weak. 2013 Retrovirology Result HIV P72A;P75A 42;47 46;51 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. LAI and LAINefP72A/P75A effectively depleted CD4+ T cells. 2013 Retrovirology Result HIV P75A 19 23 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. LAINefP72A/P75A virion RNA from plasma of the LAINefP72A/P75A infected mice from Figures 7 and 8 was processed for sequencing. 2013 Retrovirology Result HIV P75A;P75A 11;57 15;61 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. On the basis of these results, we concluded that infecting BLT mice with LAINefP72A/P75A would distinguish between the phenotypic impacts of SH3 domain binding protein dependent activities and CD4 downregulation. 2013 Retrovirology Result HIV P72A;P75A 79;84 83;88 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. SH3 domain-binding dependent activities are blocked by mutating two key prolines in Nef's polyproline helix (P72A/P75A,). 2013 Retrovirology Result HIV P72A;P75A 109;114 113;118 Nef 84 87 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Systemic depeltion of CD4+ T cells and thymocytes by LAINefP72A/P75A. 2013 Retrovirology Result HIV P75A 64 68 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Therefore, we determined the impact LAINefP72A/P75A infection in BLT mice on CD4+ T cells in bone marrow, lymph node, liver, lung and spleen (Figure 8A). 2013 Retrovirology Result HIV P75A 47 51 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. To investigate the role of the P72A/P75A mutant Nef in vivo we generated isogenic, replication competent LAINefP72A/P75A. 2013 Retrovirology Result HIV P72A;P75A;P75A 31;36;116 35;40;120 Nef 48 51 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Under these experimental conditions, a 1.9-fold higher peak viral load was observed for LAINefP72A/P75A versus LAI (Figure 7A). 2013 Retrovirology Result HIV P75A 99 103 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. We assayed the enhancement of virion infectivity for LAI and LAINefP72A/P75A and observed the expected loss of this activity for the SH3 domain binding site mutant (Figure 6C,). 2013 Retrovirology Result HIV P75A 72 76 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. We found that these cells were efficiently depleted by LAINefP72A/P75A (Figure 8B). 2013 Retrovirology Result HIV P75A 66 70 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. We, therefore, conclude that contrary to expectations the mutation, P72A/P75A has little to no effect on the systemic depletion of CD4+ T cells or CD4+ CD8+ thymocytes in vivo. 2013 Retrovirology Result HIV P72A;P75A 68;73 72;77 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. 1B) of fingers-thumb separation revealed a unimodal distribution with a peak value at ~43 A for RT-DNA, and a peak at ~47 A for RT-DNA-NVP complex and a bimodal distribution with two peaks at ~42 A and ~45 A for N348I/T369I RT-DNA-NVP complex . 2014 Proteins Result HIV N348I;T369I 212;218 217;223 RT;RT;RT 96;128;224 98;130;226 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. A kinetic study revealed that N348I mutation decreases the rate of association (Kon) of nevirapine to RT, which is apparently due to the enhanced rigidity of the NNRTI pocket caused by the connection mutation. 2014 Proteins Result HIV N348I 30 35 NNRTI;RT 162;102 167;104 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. A one-dimensional radial distribution function (RDF) calculated for the solvent around nevirapine revealed a similar profile for RT-DNA-NVP and N348I/T369I RT-DNA-NVP complexes. 2014 Proteins Result HIV N348I;T369I 144;150 149;155 RT;RT 129;156 131;158 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. A recent study hypothesized that the loss of a hydrogen bond between N348 and Y427 in p51 by N348I mutation may be responsible for the decreased RNase H activity by the mutant RT. 2014 Proteins Result HIV N348I 93 98 RT 176 178 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. A second hinge axis (axis 2) was identified for the RT-DNA-NVP and N348I/T369I RT-DNA-NVP complexes (Movies S2, S3), and the axis passed through the NNRTI-binding site. 2014 Proteins Result HIV N348I;T369I 67;73 72;78 NNRTI;RT;RT 149;52;79 154;54;81 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. A weak anti-correlated motion between fingers and thumb subdomains that appeared upon nevirapine binding was further enhanced in the N348I/T369I RT-DNA-NVP complex. 2014 Proteins Result HIV N348I;T369I 133;139 138;144 RT 145 147 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Absence of any appreciable structural changes at the global and local (NNRTI pocket) level in the N348I/T369I RT-DNA-NVP complex suggested that these mutations might propagate changes by a dynamically driven allosteric mechanism , with little or no structural change. 2014 Proteins Result HIV N348I;T369I 98;104 103;109 NNRTI;RT 71;110 76;112 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Additionally, the N348I/T369I RT-DNA-NVP complex displayed an anti-correlated motion between fingers and RNase H, which implies that N348I/T369I mutations propagate changes in structure and mobility well beyond its immediate vicinity. 2014 Proteins Result HIV N348I;N348I;T369I;T369I 18;133;24;139 23;138;29;144 RT 30 32 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Although the N348I/T369I mutations were present in both subunits, axis 3 passes through a region adjacent to the mutation sites in p51. 2014 Proteins Result HIV N348I;T369I 13;19 18;24 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. As a consequence, the N348I/T369I mutant RT-DNA-NVP complex had an increased number of hubs and stronger communities surrounding the mutation sites in both p51 and p66. 2014 Proteins Result HIV N348I;T369I 22;28 27;33 RT 41 43 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Comparison of the essential subspace spanned by RT-DNA vs RT-DNA-NVP trajectory and RT-DNA-NVP vs N348I/T369I RT-DNA-NVP trajectory were carried out by projecting the first two eigenvectors in a 2D plane. 2014 Proteins Result HIV N348I;T369I 98;104 103;109 RT;RT;RT;RT 48;58;84;110 50;60;86;112 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. DynDom analysis also predicted a third hinge axis for the N348I/T369I RT-DNA-NVP complex, which was not evident in other two complexes. 2014 Proteins Result HIV N348I;T369I 58;64 63;69 RT 70 72 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. However, N348I and other connection mutations confer significant resistance to efavirenz and etravirine only when they co-evolve with NNRTI pocket mutations. 2014 Proteins Result HIV N348I 9 14 NNRTI 134 139 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Increase in the hub residues between fingers-palm, connection-RNase H, and thumb-connection in the N348I/T369I RT-DNA-NVP complex. 2014 Proteins Result HIV N348I;T369I 99;105 104;110 RT 111 113 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. MD simulations of RT-DNA, RT-DNA-NVP, and N348I/T369I RT-DNA-NVP complexes. 2014 Proteins Result HIV N348I;T369I 42;48 47;53 RT;RT;RT 18;26;54 20;28;56 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. N348I/T369I RT-DNA-NVP were carried out for understanding how nevirapine binding alters the dynamics of RT and how the distal mutations in the connection subdomain contribute to nevirapine resistance, respectively. 2014 Proteins Result HIV T369I;N348I 6;0 11;5 RT;RT 12;104 14;106 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Residues N348 and T369 are predominantly surrounded by hydrophobic and aromatic residues and N348I/T369I mutations that enhance hydrophobicity may help form stronger hydrophobic cores surrounding the mutated residues. 2014 Proteins Result HIV N348I;T369I 93;99 98;104 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Similarly, comparison of the subspace of the RT-DNA-NVP complex in relation to mutant N348I/T369I RT-DNA-NVP reveals a wider spread in sampling. 2014 Proteins Result HIV N348I;T369I 86;92 91;97 RT;RT 45;98 47;100 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Simulations of RT-DNA-NVP and N348I/T369I RT-DNA-NVP complexes revealed fluctuations around its mean distance. 2014 Proteins Result HIV N348I;T369I 30;36 35;41 RT;RT 15;42 17;44 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The effects of the N348I/T369I mutations in both subunits are discussed in "Network analysis" section. 2014 Proteins Result HIV N348I;T369I 19;25 24;30 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The enhanced rigidity of the palm subdomain adjacent to the T215Y mutated side chain may enhance ATP binding. 2014 Proteins Result HIV T215Y 60 65 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The extent of correlation/anti-correlation is greatly enhanced in N348I/T369I RT-DNA-NVP complex, indicating that these connection domain mutations have pronounced effects on the dynamic states of RT. 2014 Proteins Result HIV N348I;T369I 66;72 71;77 RT;RT 78;197 80;199 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The fingers subdomain swiveled approximately 21 and 25 about their respective axes in RT-DNA and RT-DNA-NVP complexes, whereas this motion was restricted to ~5 in the N348I/T369I RT-DNA-NVP complex. 2014 Proteins Result HIV N348I;T369I 170;176 175;181 RT;RT;RT 88;99;182 90;101;184 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The first ten PCs accounted for 24.7, 28.8 and 44.2 % of the total variance in conformational dynamics seen in RT-DNA, RT-DNA-NVP and N348I/T369I RT-DNA-NVP complexes, respectively. 2014 Proteins Result HIV N348I;T369I 134;140 139;145 RT;RT;RT 111;119;146 113;121;148 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The free energy landscape analysis of the N348I/T369I RT-DNA-NVP complex. 2014 Proteins Result HIV N348I;T369I 42;48 47;53 RT 54 56 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. The starting model of the N348I/T369I complex was obtained by introducing the mutations in both the p66 and p51 subunits of RT-DNA-NVP structure. 2014 Proteins Result HIV N348I;T369I 26;32 31;37 RT 124 126 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. This hinge-bending motion is responsible for repositioning of the RNase H domain with respect to the polymerase active site; a maximum of ~14 and 10 rotation about axis 2 was observed for RT-DNA-NVP and N348I/T369I RT-DNA-NVP complexes, respectively; no significant rearrangement of the RNase H domain was evident in the course of simulation of the RT-DNA complex. 2014 Proteins Result HIV N348I;T369I 205;211 210;216 Pol;RT;RT;RT 101;190;217;351 111;192;219;353 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. This is in agreement with a subunit-specific kinetic study of N348I mutant RT showing that the mutation in the p51 subunit decreases RNase H activity. 2014 Proteins Result HIV N348I 62 67 RT 75 77 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. this putative effect may be analogous to the impact of L210W accompanying the T215Y/F mutation to enhance ATP binding. 2014 Proteins Result HIV L210W;T215F;T215Y 55;78;78 60;85;85 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. We carried out 50-ns simulations of RT-DNA (PDB: 1RTD), RT-DNA-NVP (PDB: ID 3V81), and the connection subdomain double mutant N348I/T369I RT-DNA-NVP structures, under conditions described in the experimental section. 2014 Proteins Result HIV N348I;T369I 126;132 131;137 RT;RT;RT 36;56;138 38;58;140 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Additionally, cation-pi interactions between R93alpha or R31beta and F139(P6-F) in H27-14-A24/Nef134-10(wt) were deformed in the case of 139L(P6L). 2013 Scientific reports Result HIV P6L 142 145 Nef;Gag;PI 94;74;21 97;76;23 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Although the number of patients with F139L was limited, the emergence of the mutation at position 139 suggests that the escape mechanism of the F139L mutant could be different from that of Y135F. 2013 Scientific reports Result HIV F139L;F139L;Y135F 37;144;189 42;149;194 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Although Y135F has been described as an example of a CTL escape mutant in both epidemiological and immunological studies, A24/Nef134-10(2F) was recognized by T36-5 and by C1-28. 2013 Scientific reports Result HIV Y135F 9 14 Nef 126 129 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. F139L appeared between Days 306 to 735 and stayed until at least 2093 days after the initial visit. 2013 Scientific reports Result HIV F139L 0 5 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. In a multicenter longitudinal acute/early infection cohort of 16 individuals expressing HLA-A24, we reconfirmed the previous finding that Y135F is selected very early after the estimated date of infection, while F139L appeared late (p = 0.0046). 2013 Scientific reports Result HIV F139L;Y135F 212;138 217;143 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. In both cohorts Y135F and F139L mutations were each significantly associated with the presence of HLA-A24 (p < 0.0001 and p = 0.0017, respectively). 2013 Scientific reports Result HIV F139L;Y135F 26;16 31;21 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Notably, the 2nd position of Nef134-10 epitope was the wild type (Y) in all IMSUT cohort patients with F139L. 2013 Scientific reports Result HIV F139L 103 108 Nef 29 32 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Taken together, these results suggested that F139L mutation could be selected weakly but substantially as a minor escape mutant under the CTL pressure against the Nef134-10 epitope. 2013 Scientific reports Result HIV F139L 45 50 Nef 163 166 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. The results confirmed the association between HLA-A24 and the Y135F mutation. 2013 Scientific reports Result HIV Y135F 62 67 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. Other common NNRTI RAMs were Y181C (n = 30; 27%), G190A (n = 26; 24%) and K101E (n = 11; 10%). 2013 AIDS research and therapy Result HIV G190A;K101E;Y181C 50;74;29 55;79;34 NNRTI 13 18 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. Other common NRTI RAMs were the K70R (n = 22; 20%), T215Y (n = 36; 24%), M41L (n = 23; 21%), D67N (n = 15; 14%), K219Q/E (n = 14; 13%) and the L210W making 9% of the TAMs. 2013 AIDS research and therapy Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215Y 93;113;113;32;143;73;52 97;120;120;36;148;77;57 NRTI 13 17 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. The commonest NNRTI RAMs was K103N (n = 59; 54%). 2013 AIDS research and therapy Result HIV K103N 29 34 NNRTI 14 19 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. The most common NRTI RAMs was the M184V (n = 89; 81%). 2013 AIDS research and therapy Result HIV M184V 34 39 NRTI 16 20 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. As individual mutations E84K and D470N each contributed to the CD4-independent phenotype but attenuated overall entry, whereas together they conferred robust entry in the presence of rmCCR5 both with and without CD4. 2013 Retrovirology Result HIV D470N;E84K 33;24 38;28 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. Conversely, when N470D and K84E were introduced into CD4-independent Envs, they reduced the ability to utilize rmCCR5 independently of CD4, but enhanced the ability to utilize low levels of rmCCR5 in the presence of CD4 (Figure 5C,D,E). 2013 Retrovirology Result HIV K84E;N470D 27;17 31;22 Env 69 73 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. D470N and E84K regulate efficiency of low-CCR5 use and GPR15 use. 2013 Retrovirology Result HIV E84K;D470N 10;0 14;5 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. E84K and D470N led to charge changes in and around the predicted CD4-binding site in gp120, with D470N introducing a potential N-linked glycosylation site that was important for CD4-independent entry. 2013 Retrovirology Result HIV D470N;D470N;E84K 9;97;0 14;102;4 gp120 85 90 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. Finally, introduction of D470N and E84K into control Envs reduced use of rmGPR15, while N470D and K84E enhanced rmGPR15 use (Figure 5F). 2013 Retrovirology Result HIV D470N;E84K;K84E;N470D 25;35;98;88 30;39;102;93 Env 53 57 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. K84E/N470D did not completely restore use of low CCR5 to the level of CD4-dependent Env (Figure 5E), suggesting that additional determinants may also contribute to efficiency of CCR5 use. 2013 Retrovirology Result HIV N470D;K84E 5;0 10;4 Env 84 87 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. We recently identified two amino acids that emerged in the CD4+ T cell-depleted macaque Envs that conferred CD4 independence when introduced into CD4-dependent Envs (D470N, E84K), and which abrogated CD4 independence when reverted in the CD4-independent Envs. 2013 Retrovirology Result HIV D470N;E84K 166;173 171;177 Env;Env;Env 88;160;254 92;164;258 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. When D470N and E84K were introduced into control Envs, they conferred CD4 independence but markedly reduced the ability of virons to enter into cells expressing low levels of rmCCR5 even in the presence of CD4 (Figure 5A,B,E). 2013 Retrovirology Result HIV D470N;E84K 5;15 10;19 Env 49 53 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. 1H-15N heteronuclear single quantum coherence (HSQC) NMR spectra were obtained for a monomeric CA construct containing mutations designed to inhibit CA-CA interactions (W184A/M185A mutations). 2013 Retrovirology Result HIV M185A;W184A 175;169 180;174 Capsid;Capsid;Capsid 95;149;152 97;151;154 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. 293T cells were cotransfected with an Env-defective pNL4-3 derivative (pNL4-3/KFS) and vectors expressing WT or V120Q/A327P Env, or VSV-G. 2013 Retrovirology Result HIV A327P;V120Q 118;112 123;117 Env;Env 38;124 41;127 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Although the low level of V120Q/A327P virus replication made the antiviral activity of the peptides difficult to assess in PBMC, it appeared that NYAD-36, -66, and -67 showed some antiviral activity against the V120Q/A327P mutant in this cell type. 2013 Retrovirology Result HIV A327P;A327P;V120Q;V120Q 32;217;26;211 37;222;31;216 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. As shown in Figure 12, both WT and V120Q/A327P virions produced from NYAD-36, -66, and -67-treated cells showed similar reductions in particle infectivity. 2013 Retrovirology Result HIV A327P;V120Q 41;35 46;40 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. However, in contrast to the results obtained in Jurkat cells, we found that replication of the V120Q/A327P mutant was severely attenuated in the PBMC from all three donors. 2013 Retrovirology Result HIV A327P;V120Q 101;95 106;100 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. In contrast, the infectivity of the V120Q/A327P double mutant was reduced by only ~2.5-fold at 50 muM NYAD-36 and NYAD-67, and less than 2-fold in the presence of NYAD-66 (Figure 9). 2013 Retrovirology Result HIV A327P;V120Q 42;36 47;41 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. In the absence of peptide, virus replication kinetics of the V120Q/A327P mutant were comparable to those of the WT. 2013 Retrovirology Result HIV A327P;V120Q 67;61 72;66 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. In two independent experiments, two mutations, V120Q and A327P, were identified in the gp120-coding portion of the env gene whereas no changes were observed in the gag gene. 2013 Retrovirology Result HIV A327P;V120Q 57;47 62;52 gp120;Env;Gag 87;115;164 92;118;167 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Jurkat cells were transfected with WT or the V120Q/A327P Env mutant derivative, and replication was monitored in the absence or presence of 37.5 muM stapled peptides. 2013 Retrovirology Result HIV A327P;V120Q 51;45 56;50 Env 57 60 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Particles bearing WT HIV-1 Env were more significantly inhibited than those bearing either the V120Q/A327P Env mutant or VSV-G (Figure 13). 2013 Retrovirology Result HIV A327P;V120Q 101;95 106;100 Env;Env 27;107 30;110 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Replication of the WT was significantly delayed (NYAD-36 or -66) or was completely blocked (NYAD-67) in the presence of peptide; in contrast, none of the three peptides had a significant effect on the replication of the V120Q/A327P mutant (Figure 10). 2013 Retrovirology Result HIV A327P;V120Q 226;220 231;225 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. The Env mutant V120Q/A327P is largely resistant to the peptide-induced entry block but remains susceptible to peptide-induced defects imposed during virus production in 293T cells. 2013 Retrovirology Result HIV A327P;V120Q 21;15 26;20 Env 4 7 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. The i,i + 7 stapled peptides retain some inhibitory activity against V120Q/A327P-mutant virions produced in the presence of peptide. 2013 Retrovirology Result HIV A327P;V120Q 75;69 80;74 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. The infectivity of both WT and the V120Q/A327P mutant was reduced to a similar extent (~10-fold) in the presence of NYAD-1 (Additional file 1: Figure S4) indicating that the gp120 mutations do not confer resistance to NYAD-1. 2013 Retrovirology Result HIV A327P;V120Q 41;35 46;40 gp120 174 179 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. These data demonstrate that the V120Q/A327P mutations in gp120 confer a marked degree of resistance to the peptides NYAD-36, -66, and -67 in single-cycle infectivity assays. 2013 Retrovirology Result HIV A327P;V120Q 38;32 43;37 gp120 57 62 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. These results demonstrate that the V120Q/A327P mutant is resistant to these stapled peptides in spreading infections in the Jurkat T-cell line. 2013 Retrovirology Result HIV A327P;V120Q 41;35 46;40 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. These results suggest that although resistance mutations map to Env, and confer resistance to the peptides both in single-cycle infectivity assays when peptide is present only at the time of infection and in replication assays, these stapled peptides are still able to exert an inhibitory activity when the V120Q/A327P mutant is produced in 293T cells in the presence of peptides. 2013 Retrovirology Result HIV A327P;V120Q 313;307 318;312 Env 64 67 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. To evaluate the effects of the peptides on replication of WT and the V120Q/A327P mutant in primary human cells, we used these viruses to infect peripheral blood mononuclear cells (PBMC) from three different donors and propagated the infected cultures in the presence of 30 muM peptide. 2013 Retrovirology Result HIV A327P;V120Q 75;69 80;74 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. V120Q is located in constant region 1(C1); A327P is at the base of the V3 loop. 2013 Retrovirology Result HIV A327P;V120Q 43;0 48;5 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. We also included as controls particles pseudotyped with WT or V120Q/A327P HIV-1 Env. 2013 Retrovirology Result HIV A327P;V120Q 68;62 73;67 Env 80 83 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. We also tested the infectivity of WT and V120Q/A327P mutant virus in the presence of the previously described peptide NYAD-1. 2013 Retrovirology Result HIV A327P;V120Q 47;41 52;46 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. We next examined whether the V120Q/A327P Env mutant is resistant to the peptides in spreading virus replication assays. 2013 Retrovirology Result HIV A327P;V120Q 35;29 40;34 Env 41 44 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. We next sought to confirm that the selected mutations confer resistance to the stapled peptides by constructing pNL4-3 derivatives containing both V120Q and A327P substitutions. 2013 Retrovirology Result HIV A327P;V120Q 157;147 162;152 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. We transfected 293T cells with WT and V120Q/A327P molecular clones, and six hours later treated with varying concentrations of stapled peptides. 2013 Retrovirology Result HIV A327P;V120Q 44;38 49;43 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. We used isothermal titration calorimetry (ITC) to estimate the binding affinity (expressed as the dissociation constant Kd) of NYAD-36, NYAD-66 and NYAD-67 to the double-mutant version (W184A/M185A) of the CA CTD. 2013 Retrovirology Result HIV M185A;W184A 192;186 197;191 Capsid 206 208 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Additionally, formation of 100 nm spherical VLPs similar to those detected in the parental sample (panels A and D) was restored, although VLPs were detected at a much lower frequency in the P7L-Y36S-S40F sample compared to the parent. 2013 Retrovirology Result HIV P7L;S40F;Y36S 190;199;194 193;203;198 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Approximately 50%, and 13% of the particles produced by pNL4-3 DeltaEnv-WT, and -S40F, respectively, possessed mature core structures (panel C). 2013 Retrovirology Result HIV S40F 81 85 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As can be seen in Figure 3, the cells transfected with P7L-S40F-Gag exhibited few of the typical virus-like particles and instead were associated with elongated particles and filopodia-like structures (Figure 3, panel B). 2013 Retrovirology Result HIV P7L;S40F 55;59 58;63 Gag 64 67 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As described above, the Y36S mutation inhibited Alix binding to Gag (Figure 4) and also L domain-2-dependent release (see below). 2013 Retrovirology Result HIV Y36S 24 28 Gag 64 67 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As described above, the yeast 2-hybrid assay revealed that the substitution of F or A for Ser40 in full-length P7L-Gag increased binding to the full-length Alix compared to the parental interaction. 2013 Retrovirology Result HIV P7L 111 114 Gag 115 118 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As expected, no signals were obtained for the negative control samples Tsg101 with P7L or P7L-Y36S paired with Alix. 2013 Retrovirology Result HIV P7L;P7L;Y36S 83;90;94 86;93;98 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As shown in Figure 7, particle production by the parental P7L-Gag construct (panel A, lane 1) was reduced significantly by introduction of the CA mutations to form CA [EE75,76AA]-p6[P7L] (lane 2) and CA[P99A]-p6[P7L] (lane 3). 2013 Retrovirology Result HIV P7L;P99A 58;203 61;207 Gag;Gag;Gag;Capsid;Capsid;Capsid 62;179;209;143;164;200 65;181;211;145;166;202 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As shown in lane 3, the introduction of the S40F mutation reduced virus production compared to the parental P7L-Gag (lane 1), P7L-Y36S-Gag (lane 2) or P7L-S40F-Gag (lane 4). 2013 Retrovirology Result HIV P7L;P7L;P7L;S40F;S40F;Y36S 108;126;151;44;155;130 111;129;154;48;159;134 Gag;Gag;Gag 112;135;160 115;138;163 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As shown in panel C, this mutation reduced Alix binding to WT Gag, P7L-S40A and P7L-S40F to the level of interaction with the negative control, Y36S-Gag. 2013 Retrovirology Result HIV P7L;P7L;S40A;S40F;Y36S 67;80;71;84;144 70;83;75;88;148 Gag;Gag 62;149 65;152 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Cells were transfected with P7L-Gag or P7L-S40F-Gag in which the P7L mutation eliminates Tsg101 binding and results in inefficient bud scission. 2013 Retrovirology Result HIV P7L;P7L;P7L;S40F 28;39;65;43 31;42;68;47 Gag;Gag 32;48 35;51 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Co-expression of P7L-S40A and Alix produced a signal that indicated their interaction (lane 8). 2013 Retrovirology Result HIV P7L;S40A 17;21 20;25 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Compared to WT, the VLPs made by pDeltaEnv-S40F appeared to remain more cell-associated (c.f., panel B). 2013 Retrovirology Result HIV S40F 43 47 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Consistent with a previous finding, we observed that S40F interfered with CA-SP1 to CA processing, mature particle formation, and viral infectivity when engineered into the pNL4-3 background. 2013 Retrovirology Result HIV S40F 53 57 SP1;Capsid;Capsid 77;74;84 80;76;86 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Disrupting Alix interaction with S40F restores spherical particle formation. 2013 Retrovirology Result HIV S40F 33 37 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Disrupting L domain-1 increases the effect of the S40F mutation on budding. 2013 Retrovirology Result HIV S40F 50 54 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Examination by immunoelectron microscopy (Figure 5) showed that formation of the membrane extensions on cells transfected with DNA encoding P7L-S40F (panels B and E) was completely suppressed in cells expressing P7L-Y36S-S40F (panels C and F). 2013 Retrovirology Result HIV P7L;P7L;S40F;S40F;Y36S 140;212;144;221;216 143;215;148;225;220 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Figure 6 shows the effect on budding when the S40F mutation was combined with disrupting mutations in both L domain-1 (P7L) and L domain-2 (Y36S) to produce P7L-Y36S-S40F. 2013 Retrovirology Result HIV P7L;P7L;S40F;S40F;Y36S;Y36S 119;157;46;166;140;161 122;160;50;170;144;165 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. However, in contrast to the single spherical VLPs which the WT produced almost exclusively, we observed that the majority of particles produced by S40F consisted either of spherical structures that remained tethered to each other in short chains or long (0.5 to 1.0 mum) membrane extensions that resembled filopodia (panels C and D). 2013 Retrovirology Result HIV S40F 147 151 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. However, S40F produced a higher percentage of immature or aberrant mature particles, as indicated by electron microscopy (panel B). 2013 Retrovirology Result HIV S40F 9 13 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Immature particles were also detected in the culture transfected with DNA encoding S40F-Gag. 2013 Retrovirology Result HIV S40F 83 87 Gag 88 91 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In addition, cells in cultures transfected with P7L-S40F possessed membrane extensions labeled with the gold-tagged probe (panel B2) indicating that Gag was associated. 2013 Retrovirology Result HIV P7L;S40F 48;52 51;56 Gag 149 152 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In contrast to WT and consistent with the results of the previous study, the particles released from cells transfected with S40F contained significant levels of CA-SP1 (p25), indicating that processing at the CA-SP1 junction was defective (panel A, lane 3). 2013 Retrovirology Result HIV S40F 124 128 SP1;SP1;Capsid;Capsid 164;212;161;209 167;215;163;211 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In contrast, ~3- to 4- fold more VLPs were detected in the media of cells expressing the mutants containing S40F (lanes 5 and 6) as compared to those lacking it (lanes 2 and 3). 2013 Retrovirology Result HIV S40F 108 112 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In contrast, as expected, the surface of cells transfected with the parental P7L-Gag accumulated single bud evaginations and tethered lollipop-like structures (panel A). 2013 Retrovirology Result HIV P7L 77 80 Gag 81 84 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In contrast, the CA[EE75,76AA]-p6[P7L] and CA[P99A]-p6[P7L] samples revealed the expected dense staining underlying the plasma membrane and no VLPs (panels B and C). 2013 Retrovirology Result HIV P99A 46 50 Gag;Gag;Capsid;Capsid 31;52;17;43 33;54;19;45 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In contrast, the double mutant, P7L-S40A-Gag was observed to increase the binding to full-length Alix an average of 7-fold compared to P7L-Gag. 2013 Retrovirology Result HIV P7L;P7L;S40A 32;135;36 35;138;40 Gag;Gag 41;139 44;142 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. In some cases, the extensions contacted neighboring cells, which is reminiscent of structures reported for HIV-infected dendritic cells where viral egress is coupled to virus-induced filopodia formation A quantitative analysis (panel C) in which ~200 gold-tagged structures were examined in each culture indicated that the P7L-S40F mutant produced the filopodia-like structures to a significantly greater extent than the P7L parent. 2013 Retrovirology Result HIV P7L;P7L;S40F 323;421;327 326;424;331 HIV infections 107 119 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Mutation of S40 to Phe (S40F), which does not alter the amino acid sequence in the overlapping pol reading frame, nevertheless inhibits CA maturation, alters budding, and reduces viral infectivity. 2013 Retrovirology Result HIV S40F 24 28 Pol;Capsid 95;136 98;138 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Our studies revealed that the effects of the P7L, Y36S and P7L-Y36S mutations, which all block budding at a late stage, were aggravated by the S40F alteration. 2013 Retrovirology Result HIV P7L;P7L;S40F;Y36S;Y36S 45;59;143;50;63 48;62;147;54;67 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Panel C shows that although gold-tagged P7L-Y36S-S40F accumulated at the cell periphery, the formation of filopodia-like structures was not induced. 2013 Retrovirology Result HIV P7L;S40F;Y36S 40;49;44 43;53;48 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Quantitative analysis indicated that VLP release efficiency was inhibited an average of 10-fold compared to P7L (n = 7 using 3 independent constructs of P7L-S40F-Gag; to ensure that this result was due to S40F, the entire Gag gene was sequenced). 2013 Retrovirology Result HIV P7L;P7L;S40F;S40F 108;153;157;205 111;156;161;209 Gag;Gag 162;222 165;225 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. S40F did not significantly affect the apparent viral budding efficiency [CA-related signal intensity in VLP/(VLP + cell lysate)], as judged by Western analysis (Figure 1, panel A3). 2013 Retrovirology Result HIV S40F 0 4 Capsid 73 75 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. S40F is therefore impacting a Gag-related assembly function. 2013 Retrovirology Result HIV S40F 0 4 Gag 30 33 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Similar results were obtained for S40F. 2013 Retrovirology Result HIV S40F 34 38 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Supporting this, examination of the CA[EE75,76AA]-p6[P7L-S40F] (panel E) and the CA[P99A]-p6[P7L-S40F] (panel F) samples by electron microscopy (Figure 8) revealed VLPs similar in size and morphology to those detected in the parental P7L sample (panel A), albeit at lower frequencies (~10-30% of parental P7L), as well as elongated particles, similar to P7L-S40F. 2013 Retrovirology Result HIV P7L;P7L;P7L;P99A;S40F;S40F;S40F;P7L;P7L 234;305;354;84;57;97;358;53;93 237;308;357;88;61;101;362;56;96 Gag;Gag;Capsid;Capsid 50;90;36;81 52;92;38;83 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The budding defects resulting from S40F mutation became increasingly more pronounced with L domain disruption, increasing in severity from reduced separation of the bud from the cell when the S40F mutation was introduced into L domain-2 (Figure 1B2) to reduced separation of buds from each other as well as from the cell when the S40F mutation was combined with L domain-1 disruption (Figures 2D; 3B2, 5E). 2013 Retrovirology Result HIV S40F;S40F;S40F 35;192;330 39;196;334 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The current study focuses on S40F. 2013 Retrovirology Result HIV S40F 29 33 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The defect resulting from S40F mutation becomes more apparent when PR is inactive. 2013 Retrovirology Result HIV S40F 26 30 PR 67 69 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The fact that similar results were obtained using two different CA mutants that exhibit the membrane curvature defect strongly suggests that the S40F mutation can complement their budding defect. 2013 Retrovirology Result HIV S40F 145 149 Capsid 64 66 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The levels of accumulation of Gag and Gag-related products inside the cells appeared comparable although the processing of CA-SP1 to CA was consistently reduced in cells expressing the S40F mutation (compare lanes 1 and 3). 2013 Retrovirology Result HIV S40F 185 189 SP1;Gag;Gag;Capsid;Capsid 126;30;38;123;133 129;33;41;125;135 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The negative controls (i.e., Tsg101 with P7L, empty vector paired with empty vector), and P7L-Y36S-Gag paired with Alix, gave no growth signal also as expected (lanes 2, 4, and 6, respectively). 2013 Retrovirology Result HIV P7L;P7L;Y36S 41;90;94 44;93;98 Gag 99 102 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The results indicate that S40F produced mature particles at a lower frequency than the WT and are consistent with the observation that the S40F mutant was more defective than the WT in CA maturation. 2013 Retrovirology Result HIV S40F;S40F 26;139 30;143 Capsid 185 187 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The results indicate that the S40F mutation impairs CA-SP1 processing, production of mature particles with conical cores, and, thereby formation of infectious virus without affecting the viral-encoded PR. 2013 Retrovirology Result HIV S40F 30 34 SP1;Capsid;PR 55;52;201 58;54;203 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40F mutation increases Alix binding to Gag in the yeast 2-hybrid assay. 2013 Retrovirology Result HIV S40F 4 8 Gag 44 47 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40F mutation increases the disruption of virus release due to nonfunctional L domains-1 and -2. 2013 Retrovirology Result HIV S40F 4 8 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40F mutation partially rescues the block to budding imposed by mutations in the CA NTD. 2013 Retrovirology Result HIV S40F 4 8 Capsid 85 87 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The same three types of particles were found when cells were transfected with pNL4-3DeltaEnvS40F (panel B, right) except that the S40F mutant produced significantly fewer particles with conical cores and relatively more immature VLPs (open arrow) and VLPs with aberrant cores (gray arrow). 2013 Retrovirology Result HIV S40F;S40F 130;92 134;96 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The VLPs produced by P7L-Gag were labeled with the gold-tagged antibody probe (panel A2), as expected. 2013 Retrovirology Result HIV P7L 21 24 Gag 25 28 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The yeast 2-hybrid assay (Y2H) for protein-protein interaction has been used in several previous studies to assess HIV-1 Gag-Alix interaction. 2013 Retrovirology Result HIV Y2H 26 29 Gag 121 124 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. This indicated that the S40F mutation alleviated the defect imposed by the CA mutations, at least partially. 2013 Retrovirology Result HIV S40F 24 28 Capsid 75 77 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. This indicated that the S40F mutation impacted these mutants in a positive manner, in contrast to its effect on the p6 and CA CTD budding determinants. 2013 Retrovirology Result HIV S40F 24 28 Gag;Capsid 116;123 118;125 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Thus, the impact of S40F is surprising. 2013 Retrovirology Result HIV S40F 20 24 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Thus, the S40F mutation appeared to partially rescue the early budding defect imposed by mutation of the CA NTD determinants and to aggravate the block to late budding directed by the CA CTD and p6 determinants. 2013 Retrovirology Result HIV S40F 10 14 Gag;Capsid;Capsid 195;105;184 197;107;186 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Thus, under these conditions, where both L domain-1 and -2 were disrupted, the budding defect resulting from the S40F mutation was even more pronounced, i.e., manifested in a significant block to viral particle release from cells. 2013 Retrovirology Result HIV S40F 113 117 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. To confirm the previously observed processing defect of S40F, we engineered the mutation into pNL4-3-DeltaEnv and examined Gag processing products by Western analysis. 2013 Retrovirology Result HIV S40F 56 60 Gag 123 126 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. To determine whether the S40F mutation affected viral assembly prior to particle budding, the L domain-1 (P7TAP) was mutated to inhibit virus release. 2013 Retrovirology Result HIV S40F 25 29 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. To determine whether the S40F mutation impacts the phenotype resulting from the CA mutations, we constructed CA[EE75,76AA]-p6[P7L-S40F] and CA[P99A]-p6[P7L-S40F] and investigated VLP release efficiency by Western analysis. 2013 Retrovirology Result HIV P99A;S40F;S40F;S40F;P7L;P7L 143;25;130;156;126;152 147;29;134;160;129;155 Gag;Gag;Capsid;Capsid;Capsid 123;149;80;109;140 125;151;82;111;142 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. To ensure that the enhancing effect of the S40 mutation was directly attributable to Alix binding to the LYPX2SL motif in the p6 region, the inactivating mutation F676D was introduced into the interacting V domain of Alix. 2013 Retrovirology Result HIV F676D 163 168 Gag 126 128 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. To evaluate viral particle infectivity, cells were co-transfected with plasmids pNL4-3DeltaEnv-WT, or -S40F and pIIIB-Env-3-1 and the specific infectivity per ng p24 in the cleared cell media was determined in single-round assays using MAGI cells. 2013 Retrovirology Result HIV S40F 103 107 p24;Env 162;118 165;121 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. To examine this possibility, we choose to block Gag-Alix interaction by introducing the Y36S mutation into the Gag-P7L-S40F construct. 2013 Retrovirology Result HIV P7L;S40F;Y36S 115;119;88 118;123;92 Gag;Gag 48;111 51;114 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Unexpectedly, the mutation of S40 to A, a change that alters the amino acid sequence at the p6*-PR cleavage site in the overlapping pol frame, resulted in WT levels of CA-SP1 to CA processing, as assessed by Western blotting: VLPs released from cells expressing S40A exhibited no defect in CA-SP1 to CA processing (Figure 1, panel A, lane 2). 2013 Retrovirology Result HIV S40A 262 266 Pol;SP1;SP1;Gag;Capsid;Capsid;Capsid;Capsid;PR 132;171;293;92;168;178;290;300;96 135;174;296;94;170;180;292;302;98 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. VLP release efficiency was not affected for the P7L-S40F mutant in comparison to P7L (panel D, Western blot analysis; panel E, VLP release efficiency). 2013 Retrovirology Result HIV P7L;P7L;S40F 48;81;52 51;84;56 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. When tested on the triple drop-out media (TDO, Trp, Leu and His), which tests for protein-protein interaction, the positive controls [i.e., full-length Alix paired with P7L-Gag, Tsg101 paired with WT Gag, and T Ag paired with p53 (lanes 1, 7 or 9; 3 and 5, respectively)] interacted, as expected. 2013 Retrovirology Result HIV P7L 169 172 Gag;Gag 173;200 176;203 24268781 Link between primate lentiviral coreceptor usage and Nef function. Combined changes of I123L and L146F disrupted the CD3 downmodulation activity in early SIVsmm SM2 Nefs, whereas the reciprocal revertant changes restored this activity in late inactive Nefs (Figure 5B). 2013 Cell reports Result HIV I123L;L146F 20;30 25;35 Nef;Nef 98;185 102;189 24268781 Link between primate lentiviral coreceptor usage and Nef function. Comparison of the functional activity of SIVsmm Nefs differing in these residues showed that Nefs containing the I123L and L146F substitutions were inactive in CD3 downmodulation, whereas those containing the I132V change showed an intermediate phenotype (Figure 5A). 2013 Cell reports Result HIV I123L;I132V;L146F 113;209;123 118;214;128 Nef;Nef 48;93 52;97 24268781 Link between primate lentiviral coreceptor usage and Nef function. Consistent with their inability to downmodulate TCR-CD3, no interaction was detected for the 75w-L4 I123L/L146F and wild-type 304w-H1 Nefs (Figures 5D and 5E). 2013 Cell reports Result HIV L146F;I123L 106;100 111;105 Nef 134 138 24268781 Link between primate lentiviral coreceptor usage and Nef function. In contrast, CD8-CD3zeta-GFP fluorescence was detected exclusively in intracellular perinuclear compartments in the presence of the SIVmac239, SIVsmm SM2 75w-L4, and 304-H1 L123I/F146L Nefs. 2013 Cell reports Result HIV F146L;L123I 179;173 184;178 Nef 185 189 24268781 Link between primate lentiviral coreceptor usage and Nef function. In the absence of Nef or in the presence of the HIV-1 NL4-3 and SIVsmm SM2 75-L4 I123L/L146F or 304-H1 Nef proteins, the CD8-CD3 fusion was detected at both the plasma membrane and the perinuclear regions of the cells (Figure 5F). 2013 Cell reports Result HIV L146F;I123L 87;81 92;86 Nef;Nef 18;103 21;106 24268781 Link between primate lentiviral coreceptor usage and Nef function. Next, we examined the effect of the I123L and L146F substitutions on the ability of Nef to modulate the subcellular localization of TCR-CD3. 2013 Cell reports Result HIV I123L;L146F 36;46 41;51 Nef 84 87 24268781 Link between primate lentiviral coreceptor usage and Nef function. Notably, a naturally occurring amino acid variation at this position (I132T) specifically disrupts the CD3 downmodulation activity of HIV-2 Nef. 2013 Cell reports Result HIV I132T 70 75 Nef 140 143 24268781 Link between primate lentiviral coreceptor usage and Nef function. Notably, the I123L and L146F changes always occurred in combination with one another, but never together with the I132V substitution (Figure S3). 2013 Cell reports Result HIV I123L;I132V;L146F 13;114;23 18;119;28 24268781 Link between primate lentiviral coreceptor usage and Nef function. Our results showed that the SIVmac239 Nef as well as SIVsmm 75w-L4 and 304w-H1 L123I/F146L Nefs were effective in pulling down CD3zeta (Figure 5D) and resulted in significant FRET signals (Figure 5E). 2013 Cell reports Result HIV F146L;L123I 85;79 90;84 Nef;Nef 38;91 41;95 24268781 Link between primate lentiviral coreceptor usage and Nef function. Sequence alignments showed that active and inactive Nefs from SM2 differed by amino acid changes of I123L and L146F (Figure S3). 2013 Cell reports Result HIV I123L;L146F 100;110 105;115 Nef 52 56 24268781 Link between primate lentiviral coreceptor usage and Nef function. The I123L and L146F changes in Nef also affected the responsiveness of virally infected cells to stimulation and the induction of apoptosis but had no significant effect on other Nef activities, such as modulation of CD4, CD28, CXCR4, and MHC-I or enhancement of virion infectivity (data not shown). 2013 Cell reports Result HIV I123L;L146F 4;14 9;19 Nef;Nef 31;179 34;182 24268781 Link between primate lentiviral coreceptor usage and Nef function. The SIVsmm SM2 75w-L4 and mutant 304w-H1 L123I/F146L Nefs also accelerated internalization of TCR-CD3, whereas the 75w-L4 I123L/L146F and wild-type 304w-H1 Nefs had no significant effect (Figure 5C). 2013 Cell reports Result HIV F146L;L146F;I123L;L123I 47;128;122;41 52;133;127;46 Nef;Nef 53;156 57;160 24268781 Link between primate lentiviral coreceptor usage and Nef function. The temporal appearance of different nef substitutions suggested a timeline where Nef-mediated CD3 downmodulation was initially reduced by the I132V substitution and later disrupted entirely by the I123L and L146F substitutions. 2013 Cell reports Result HIV I123L;I132V;L146F 198;143;208 203;148;213 Nef;Nef 37;82 40;85 24268781 Link between primate lentiviral coreceptor usage and Nef function. These two substitutions were preceded by a substitution of I132V in SM2, and this change was also observed in most Nef alleles derived from SM1 at later time points (>=107 wpi). 2013 Cell reports Result HIV I132V 59 64 Nef 115 118 24268781 Link between primate lentiviral coreceptor usage and Nef function. Thus, the I123L and L146F changes may shift the position of the two helices relative to each other and thus alter the size and structure of the associated binding pocket in such a way that it becomes inaccessible for the CD3zeta chain but still accommodates the cytoplasmic domain of CD4, which binds the same hydrophobic crevice. 2013 Cell reports Result HIV I123L;L146F 10;20 15;25 24268781 Link between primate lentiviral coreceptor usage and Nef function. Thus, the microscopy analyses confirmed that the I123L and L146F changes disrupt the ability of Nef to remove TCR-CD3 from the cells surface. 2013 Cell reports Result HIV I123L;L146F 49;59 54;64 Nef 96 99 24268781 Link between primate lentiviral coreceptor usage and Nef function. To better understand how the I123L/L146F changes affected Nef-mediated modulation of TCR-CD3, we examined the localization of these residues in the crystal structure of the SIVmac239 Nef core domain complexed with the first ITAM motif of the CD3zeta chain. 2013 Cell reports Result HIV I123L;L146F 29;35 34;40 Nef;Nef 58;183 61;186 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. Collectively, the data demonstrate antiviral activity of RV against HIV-1 carrying the M184V mutation, alone or in combination with other mutations in RT. 2014 AIDS (London, England) Result HIV M184V 87 92 RT 151 153 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. In each WT/M184V virus pair, RV inhibited M184V mutant (EC50 values ranging between 2.5 and 6.7 microM), but not WT (EC50 > 10 microM). 2014 AIDS (London, England) Result HIV M184V;M184V 11;42 16;47 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. RV failed to inhibit drug-resistant NL4-3 clones lacking the M184V mutation, but inhibited all drug-resistant clones containing M184V (EC50 values ranging between 2.7 and 5.8 microM). 2014 AIDS (London, England) Result HIV M184V;M184V 61;128 66;133 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. RV inhibits FTC-resistant HIV-1 carrying the M184V mutation. 2014 AIDS (London, England) Result HIV M184V 45 50 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. RV inhibits multi-drug resistant viruses carrying the M184V mutation. 2014 AIDS (London, England) Result HIV M184V 54 59 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. Similar to the data with NL4-3 molecular clones, RV inhibited the multi-drug resistant isolate with the M184V mutation but not those lacking it. 2014 AIDS (London, England) Result HIV M184V 104 109 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. The M184V mutation is frequently observed in conjunction with RT mutations conferring resistance to other NRTIs. 2014 AIDS (London, England) Result HIV M184V 4 9 NRTI;RT 106;62 111;64 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. These results demonstrate that RV has antiviral activity against viruses with the M184V mutation as the sole mutation in RT. 2014 AIDS (London, England) Result HIV M184V 82 87 RT 121 123 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. We chose viruses with M184V as single mutation to avoid confounding of the data by additional mutations that might compensate for the viral growth disadvantage conferred by M184V. 2014 AIDS (London, England) Result HIV M184V;M184V 22;173 27;178 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. We next evaluated RV against HIV-1 primary isolate pairs, with and without the M184V mutation as the sole mutation in RT, derived from the same patient. 2014 AIDS (London, England) Result HIV M184V 79 84 RT 118 120 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Additionally, the S173T adjacent to epitope KF11, and mutations V159I and T280V were associated with the presence of HLA-B*57/58:01 (Figure 1A, Table 2 and Table S1). 2013 PloS one Result HIV S173T;T280V;V159I 18;74;64 23;79;69 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Among these HLA-B*57/58:01 specific amino acid mutations were the HLA-B*57/58:01 associated CTL escape mutations T242N and G248A located in the TW10 epitope and the I147L mutation in the IW9 epitope. 2013 PloS one Result HIV G248A;I147L;T242N 123;165;113 128;170;118 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. An increase in viral replication was observed after introduction of the L215T and H219Q mutation (p = 0.002 and p = 0.0002 respectively, Figure 1D; Figure S1A), whereas mutations S126N and M228I did not alter replication kinetics (Figure1D and Figure S1A). 2013 PloS one Result HIV H219Q;L215T;M228I;S126N 82;72;189;179 87;77;194;184 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. As mutations L215T and H219Q show the highest increase in replication capacity analyzing the single mutations, we also introduced a combination of these two mutations in the mutant virus carrying the 6 HLA-B*57/58:01-specific mutations. 2013 PloS one Result HIV H219Q;L215T 23;13 28;18 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Frequent variation in amino acid composition was observed at 5 positions within Gag (S126N, L215T, H219Q, M228I and N252H) in viral sequences obtained from progressors, whereas these amino acids were absent or only present at low frequency in sequences obtained from LTNPs (Table 3, Figure 1B and Table S1). 2013 PloS one Result HIV H219Q;L215T;M228I;N252H;S126N 99;92;106;116;85 104;97;111;121;90 Gag 80 83 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. In order to study the effects of the sequence variation found, the mutations associated with disease progression (alone or in combination) were placed in the NL4-3.Ba-L molecular clone together with the 6 mutations specifically associated with the presence of HLA-B*57/58:01 (T242N, G248A, I147L, S173T, V159I and T280V) (Tables 2 and 3). 2013 PloS one Result HIV G248A;I147L;S173T;T242N;T280V;V159I 283;290;297;276;314;304 288;295;302;281;319;309 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. reported that the compensatory mutations H219Q, I223V, M228I, G248A and N252H partially restored replication kinetics of NL4-3 virus carrying the T242N escape mutation. 2013 PloS one Result HIV G248A;H219Q;I223V;M228I;N252H;T242N 62;41;48;55;72;146 67;46;53;60;77;151 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. The I223V mutation alone had no significant effect on the replication kinetics of NL4-3.Ba-L carrying the HLA-B*57/58:01 specific mutations (Figure 1E and Figure S1B). 2013 PloS one Result HIV I223V 4 9 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. The I223V mutation was not observed to be different between LTNPs and progressors in our analysis, nor was it associated with the presence of HLA-B*57/58:01. 2013 PloS one Result HIV I223V 4 9 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. The NL4-3.Ba-L molecular clone backbone already contains N252H, and this amino acid was not changed in the constructed viruses. 2013 PloS one Result HIV N252H 57 62 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Three of these mutations (H219Q, M228I, N252H) were also associated with disease progression in our analysis, while the G248A mutation was found in all HLA-B*57/58:01 patients irrespective of their disease course. 2013 PloS one Result HIV G248A;H219Q;M228I;N252H 120;26;33;40 125;31;38;45 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. Compared to the WTp1-p6WT complex, P1 and P1' in SP3'Np1-p6D30N/n88D have slightly less favorable interactions with the PR, on the order of total 1 kcal/mol (Figure 3C). 2012 Journal of chemical theory and computation Result HIV D30N 59 63 Gag;PR 57;120 59;122 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. For example, the PR: substrate vdW interaction potential of WTp1-p6D30N/N88D is 1.9 +- 0.2 kcal/mol (Figure 1H) less favorable than that of WTp1-p6WT. 2012 Journal of chemical theory and computation Result HIV D30N;N88D 67;72 71;76 Gag;PR 65;17 67;19 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. However, both AP2VNC-p1WT and AP2VNC-p1V82A have more consistent hydrogen bonds formed by P1 and I50 and G27. 2012 Journal of chemical theory and computation Result HIV V82A 39 43 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In addition, P2 in LP1'Fp1-p6D30N/N88D does not interact with the PR as favorably as P2 in WTp1-p6D30N/N88D (DeltavdW = -4.0 +- 0.1 kcal/mol), even though P2 is invariant. 2012 Journal of chemical theory and computation Result HIV D30N;D30N;N88D;N88D 29;98;34;103 33;102;38;107 Gag;Gag;PR 27;96;66 29;98;68 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In addition, the P1, P2', and P3' positions make backbone hydrogen bonds with the PR in SP3'Np1-p6D30N/N88D (Table 2). 2012 Journal of chemical theory and computation Result HIV D30N;N88D 98;103 102;107 Gag;PR 96;82 98;84 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In coevolution of NC-p1 cleavage site, DeltaVin increases from :26.3 +- 1.9 A3 in WTNC-p1V82A complex to 4.2 +- 1.8 A3 in AP2VNC-p1V82A (Figure 1A), while in coevolution of p1-p6 cleavage site, DeltaVin increases from :122.2 +- 1.5 A3 in WTp1-p6D30N/N88D to 8.2 +- 1.3A3 in LP1'Fp1-p6D30N/N88D (Figure 1B) and to :48.5 +- 1.8 A3 in SP3'Np1-p6D30N/N88D (Figure 1C). 2012 Journal of chemical theory and computation Result HIV D30N;D30N;D30N;V82A;V82A;N88D;N88D;N88D 245;284;342;89;131;250;289;347 249;288;346;93;135;254;293;351 NC;Gag;Gag;Gag;Gag 18;176;243;282;340 20;178;245;284;342 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In contrast, WTNC-p1V82A has -4.6 +- 0.2 kcal/mol more favorable vdW interactions compared to WTNC-p1WT (Figure 1G). 2012 Journal of chemical theory and computation Result HIV V82A 20 24 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In SP3'Np1-p6D30N/N88D complex, on the other hand, no intramolecular hydrogen bond exists more than 50% of the time, suggesting that these hydrogen bonds are not necessary for this variant to adopt the required three-dimensional shape that fits the binding groove. 2012 Journal of chemical theory and computation Result HIV D30N;N88D 13;18 17;22 Gag 11 13 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. Loss of interactions at P4' position in LP1'Fp1-p6D30N/N88D with respect to WTp1-p6WT (2.3 +- 0.1 kcal/mol, Figure 3B, green bars) is compensated by the gain of interactions at two other substrate residues, P1 (-2.3 +- 0.1 kcal/mol) and P2' (-1.1 +- 0.1 kcal/mol). 2012 Journal of chemical theory and computation Result HIV D30N;N88D 50;55 54;59 Gag 48 50 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. LP1'Fp1-p6D30N/N88D has almost the same pattern of hydrogen-bonding network as WTp1-p6WT (Figure 5D). 2012 Journal of chemical theory and computation Result HIV D30N;N88D 10;15 14;19 Gag 8 10 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. LP1'Fp1-p6D30N/N8D has more favorable P4' interactions than WTp1-p6D30N/N8D, although the loss of interaction potential at this position is considerably higher than WTp1-p6WT. 2012 Journal of chemical theory and computation Result HIV D30N;D30N;N8D;N8D 10;67;15;72 14;71;18;75 Gag;Gag 8;65 10;67 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. On the other hand, the reduction in Vout is 96.2 +- 2.8 and 11.8 +- 3.3 A3 (Figure 1E and F, respectively) upon LP1'F and SP3'N occurs in the context of D30N/N88D PR variant. 2012 Journal of chemical theory and computation Result HIV D30N;N88D 153;158 157;162 PR 163 165 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. Preservation of substrate envelope upon compensatory cleavage site mutations in drug-resistant PR variants is visualized in Figure 2 in the case of LP1'Fp1-p6D30N/N88D. 2012 Journal of chemical theory and computation Result HIV D30N;N88D 158;163 162;167 Env;Gag;PR 26;156;95 34;158;97 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. Similarly, in LP1'Fp1-p6D30N/N88D, LP1'F mutation restores the hydrogen bond between P2 and P1' positions of the substrate that is lost upon D30N/N88D PR mutations in WTp1-p6D30N/N88D. 2012 Journal of chemical theory and computation Result HIV D30N;D30N;D30N;N88D;N88D;N88D 24;174;141;29;146;179 28;178;145;33;150;183 Gag;Gag;PR 22;172;151 24;174;153 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. Similarly, in the presence of D30N/N88D mutations in the PR, LP1'F and SP3'N substitutions in p1-p6 improve Vin by 130.4 +- 2.0 and 73.7 +- 2.3 A3 (Figure 1B and C, respectively), making the substrate better fill the substrate envelope. 2012 Journal of chemical theory and computation Result HIV D30N;N88D 30;35 34;39 Env;Gag;PR 227;97;57 235;99;59 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. Substitution of Val-82 to an Ala results in a larger local volume for this flexible peptide to sample. 2012 Journal of chemical theory and computation Result HIV V82A 16 32 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The altered fit of p1-p6 within the dynamic substrate envelope in WTp1-p6D30N/N88D and LP1'Fp1-p6D30N/N88D (Figure 2A and B, respectively) complexes is illustrated by mapping the DeltaVin grid matrix onto the cocrystal structure. 2012 Journal of chemical theory and computation Result HIV D30N;D30N;N88D;N88D 73;97;78;102 77;101;82;106 Env;Matrix;Gag;Gag;Gag 54;193;22;71;95 62;199;24;73;97 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The loss of this interaction due to D30N/N88D PR mutations is restored with LP1T and SP3 N substitutions in the cleavage site to a level of -1.7 +- 0.2 and -3.2 +- 0.2 kcal/mol (Figure 1H and I, respectively). 2012 Journal of chemical theory and computation Result HIV D30N;N88D 36;41 40;45 PR 46 48 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The majority of these bonds are preserved in drug-resistant WTp1-p6D30N/N88D, although the bond between backbone nitrogen of P1 and backbone oxygen of G27 no longer exists in WTp1-p6D30N/N88D (Figure 5C). 2012 Journal of chemical theory and computation Result HIV D30N;D30N;N88D;N88D 67;182;72;187 71;186;76;191 Gag;Gag 65;180 67;182 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The p1-p6 substrate appears to be highly cooperative in both LP1'Fp1-p6D30N/N88D and SP3'Np1-p6D30N/N88D complexes compared to WTp1-p6WT (Figure 7). 2012 Journal of chemical theory and computation Result HIV D30N;D30N;N88D;N88D 71;95;76;100 75;99;80;104 Gag;Gag;Gag 7;69;93 9;71;95 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The same substrate sequence behaves slightly differently in WTp1-p6D30N/N88D (Figure 7B), where the P4-P1 and P1'-P4' residues define the two regions that fluctuate independently. 2012 Journal of chemical theory and computation Result HIV D30N;N88D 67;72 71;76 Gag 65 67 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The three complexes of WTp1p6WT, WTp1-p6D30N/N88D, and LP1'Fp1-p6D30N/N88D are superimposed to highlight these rearrangements (Figure 5A and E.). 2012 Journal of chemical theory and computation Result HIV D30N;D30N;N88D;N88D 40;65;45;70 44;69;49;74 Gag;Gag 38;63 40;65 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. The viral advantage of weakening highly consistent hydrogen bonds formed in LP1'Fp1p6D30N/N88D could be to optimize substrate binding for optimal viral fitness. 2012 Journal of chemical theory and computation Result HIV D30N;N88D 85;90 89;94 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. These presumably stronger hydrogen bonds might be important for the increased substrate affinity in both AP2VNC-p1WT and AP2VNC-p1V82A variants, consistent with AP2VNC-p1 being more efficiently cleaved than WTNC-p1 by the WT HIV-1 PR. 2012 Journal of chemical theory and computation Result HIV V82A 130 134 PR 231 233 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. This analysis showed that WTNC-p1V82A is less cooperative compared to WTNC-p1WT (Figure 6A versus B). 2012 Journal of chemical theory and computation Result HIV V82A 33 37 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. This bond is lost upon V82A mutation in the PR but compensated by the secondary mutation AP2V in AP2VNC-p1V82A. 2012 Journal of chemical theory and computation Result HIV V82A;V82A 106;23 110;27 PR 44 46 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. This may be the reason why (1) on average, AP2VNC-p1V82A variants have lower replicative capacity than WTNC-p1V82A, and (2) the more efficiently cleaved AP2VNC-p1 is not highly populated in the absence of drug resistance mutations in the PR. 2012 Journal of chemical theory and computation Result HIV V82A;V82A 52;110 56;114 PR 238 240 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. This observation is quantified in Figure 1A:C, where Vin is plotted for three cases of coevolution (AP2VNC-p1V82A, LP1'F p1-p6D30N/N88D, and SP3'Np1-p6D30N/N88D) with reference to their respective WT complex structure . 2012 Journal of chemical theory and computation Result HIV D30N;D30N;V82A;N88D;N88D 126;151;109;131;156 130;155;113;135;160 Gag;Gag 124;149 126;151 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. WTp1-p6D30N/N88D has consistent PR-substrate side-chain hydrogen bonds formed by P2 and P2' residues (Figure 5G). 2012 Journal of chemical theory and computation Result HIV N88D 12 16 Gag;PR 5;32 7;34 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. WTp1-p6D30N/N88D loses 4.3 +- 2.0 kcal/mol vdW interactions at the P4' position and gains comparable interactions at the P2 position (-4.0 +- 0.9 kcal/mol, Figure 3B, blue bars). 2012 Journal of chemical theory and computation Result HIV D30N;N88D 7;12 11;16 Gag 5 7 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Additionally, M46I/L mutations were not detected in the minority L90M amplicon indicating these mutations were not linked. 2013 PloS one Result HIV L90M;M46I;M46L 65;14;14 69;20;20 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. All genotype M46L samples were positive (DeltaCT ranged from 0.88 to 8.95 cycles) (Figure 3 and Table S3). 2013 PloS one Result HIV M46L 13 17 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. As summarized in Table 2, all resistant mutations were found as sole mutation, one with A62V, one with D67E and six cases of intermediates at codon 215 (one with T215D, one with T215E, two cases of T215L and two cases of T215S), one with N88D and 14 cases of M46I mutation were detected by conventional bulk sequencing analysis, yielding a drug resistance mutation prevalence of 15.4% (23/149 cases) (Table 2). 2013 PloS one Result HIV A62V;D67E;M46I;N88D;T215D;T215E;T215L;T215S 88;103;259;238;162;178;198;221 92;107;263;242;167;183;203;226 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. At this cutoff, all 55 genotyped M46I samples were positive (DeltaCTs ranged from 1.39 to 10.1 cycles, Figure 3 and Table S3). 2013 PloS one Result HIV M46I 33 37 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Extrapolating from the dilution curve for cloned M46I sequences, this cycle difference corresponded to a frequency mean of 0.54% mutant virus (see Table S3). 2013 PloS one Result HIV M46I 49 53 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. For M46L assay, DeltaCT cutoff was 9 cycles to avoid low-level amplification from spurious primer binding against clinical quasispecies specimens; this cutoff placement corresponded to a frequency mean of 4.01% mutant virus. 2013 PloS one Result HIV M46L 4 8 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. High sensitivity and specificity of M46I/L detection assays confirmed with clinical samples. 2013 PloS one Result HIV M46I;M46L 36;36 42;42 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In assessing the relatedness of the four detected minority L90M to infections that have the PR M46I mutation, three L90M were from patients that were wildtype at codon 46, the fourth was ID 13 which was also an M46I case (Figure 4B). 2013 PloS one Result HIV L90M;L90M;M46I;M46I 59;116;95;211 63;120;99;215 PR 92 94 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In ID 22, the M46I amplicon matched the bulk sequence. 2013 PloS one Result HIV M46I 14 18 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In ID 27, A71T was detected in the M46L amplicon, but this mutation was not found in the M46I amplicon or the bulk sequence (Table 3). 2013 PloS one Result HIV A71T;M46I;M46L 10;89;35 14;93;39 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In ID 29, the I72V polymorphism observed in the bulk sequence was detected in M46L and L90M amplicons, but not in the M46I amplicon (Table 3). 2013 PloS one Result HIV I72V;L90M;M46I;M46L 14;87;118;78 18;91;122;82 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In one case, six mutations, M41L, K70R, M184V, M46I, M46L and L90M were detected as minority mutations by the highly sensitive assays (ID 29). 2013 PloS one Result HIV K70R;L90M;M184V;M41L;M46I;M46L 34;62;40;28;47;53 38;66;45;32;51;57 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. In other cases, K70R and M46I were detected (ID 22), and M46I and M46L were detected in another case as minority drug resistance mutations (ID 5). 2013 PloS one Result HIV K70R;M46I;M46I;M46L 16;25;57;66 20;29;61;70 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Minority M46I could be detected as low as 0.04% and M46L could be detected as low as 0.03% in site-directed mutant clones. 2013 PloS one Result HIV M46I;M46L 9;52 13;56 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Moreover, some of the patients with bulk sequence-detectable M46I appeared to group together with relatively high bootstrap values (pairs X and Y, Figure 4A) and may represent infections linked within transmission clusters. 2013 PloS one Result HIV M46I 61 65 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Relative limits of detection were compared in a simple laboratory setting using serial dilutions of HXB2-M46I or HXB2-M46L in backgrounds of HXB2 wildtype plasmid. 2013 PloS one Result HIV M46I;M46L 105;118 109;122 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Sequence analysis of M46I and M46L-specific amplicons showed that these mutations were not linked to L90M in the patient samples. 2013 PloS one Result HIV L90M;M46I;M46L 101;21;30 105;25;34 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. The assay cutoffs selected based on plasmid sequences were evaluated against clinical specimens using a total of 55 samples with sequence-detectable M46I mutation and a total 22 samples with sequence-detectable M46L mutation. 2013 PloS one Result HIV M46I;M46L 149;211 153;215 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. The DeltaCT that was equivalent to a 0.5 log greater reactivity than the wild-type mean DeltaCT on the dilution curve (M46I : CT=15 cycles, M46L : CT=17 cycles) was used to compare assay sensitivities (Figure 2). 2013 PloS one Result HIV M46I;M46L 119;141 124;145 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. The identified A62V, D67E, T215E, T215S and N88D mutations detected by bulk sequencing were not targeted by AS-PCR, and therefore were not included in determining changes in mutation frequency. 2013 PloS one Result HIV A62V;D67E;N88D;T215E;T215S 15;21;44;27;34 19;25;48;32;39 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. The resulting distribution of collated DeltaCTs from the wild-type samples supported a DeltaCT cutoff of 11 cycles for M46I clinical testing (DeltaCTs ranged from 16.39-26.65 cycles) (Figure 3 and Table S3). 2013 PloS one Result HIV M46I 119 123 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. The sensitive screening detected an additional one case of M41L (0.67%), two cases of K65R (1.34%), two cases of K70R (1.34%), one case of M184V (0.67%), 15 cases of M46I (19.46%), 5 cases of M46L (3.36%) and 4 cases of L90M (2.68%) as minority-level drug resistance mutations (Table 2). 2013 PloS one Result HIV K65R;K70R;L90M;M184V;M41L;M46I;M46L 86;113;220;139;59;166;192 90;117;224;144;63;170;196 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. This approach yielded detection limits of 0.04% and 0.03% for M46I and M46L, respectively. 2013 PloS one Result HIV M46I;M46L 62;71 66;75 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. To analyze the linkage between drug resistance mutations, we directly sequenced positive M46I/L or L90M-specific PCR products to ascertain whether additional genotypic information could be obtained from those amplicons. 2013 PloS one Result HIV L90M;M46I;M46L 99;89;89 103;95;95 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Although expression levels of W21A, W89A and E88A/W89A mutants were higher than wild-type, endogenous CBFbeta did not co-precipitate with these mutants. 2014 Virology Result HIV E88A;W21A;W89A;W89A 45;30;36;50 49;34;40;54 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Although we transfected with the same amount of plasmid DNA, expression levels of E88A, W38A, D14/R15AA, Y40A, Y69A and G84D were comparable to wild-type Vif, but those of W89A, E88/W89A and W21A mutants were obviously impaired. 2014 Virology Result HIV R15A;W89A;E88A;G84D;W21A;W38A;W89A;Y40A;Y69A 98;182;82;120;191;88;172;105;111 102;186;86;124;195;92;176;109;115 Vif 154 157 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Because W21 and W38 are close to A3G binding residues of Vif, 40YRHHY44, the loss of A3G degradation by W21A or W38A might be caused by loss of A3G binding. 2014 Virology Result HIV W21A;W38A 104;112 108;116 Vif 57 60 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Co-transfection of wild-type Vif reduced APOBEC3G levels, but E88A/W89A, W21A or W38A did not. 2014 Virology Result HIV E88A;W21A;W38A;W89A 62;73;81;67 66;77;85;71 Vif 29 32 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. E88A or W89A reduced A3G levels close to wild-type Vif. 2014 Virology Result HIV W89A;E88A 8;0 12;4 Vif 51 54 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Endogenous CUL5 appeared to co-precipitate with wild-type Vif, but not with W21A, W38A, W89A, or E88A/W89A. 2014 Virology Result HIV E88A;W21A;W38A;W89A;W89A 97;76;82;88;102 101;80;86;92;106 Vif 58 61 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. In the presence of A3G, virus with E88A mutation showed comparable infectivity to wild-type, but virus with W21A, W38A or E88A/W89A showed deeply impaired infectivity close to that of DeltaVif. 2014 Virology Result HIV E88A;E88A;W21A;W38A;W89A 35;122;108;114;127 39;126;112;118;131 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. More importantly, endogenous CBFbeta co-precipitated with wild-type Vif, D14A/R15A, Y40A, G84D, and E88A, but not with W21A, W89A, or E88A/W89A. 2014 Virology Result HIV D14A;E88A;E88A;G84D;R15A;W21A;W89A;W89A;Y40A 73;100;134;90;78;119;125;139;84 77;104;138;94;82;123;129;143;88 Vif 68 71 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. To exclude the possibility that low expression of W21A, W89A and E88A/W89A mutants caused the low amount of co-immunoprecipitated CBFbeta, we adjusted the amount of plasmid DNA transfected, and performed co-immunoprecipitation experiments. 2014 Virology Result HIV E88A;W21A;W89A;W89A 65;50;56;70 69;54;60;74 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. To test our hypothesis that conserved residues E88 and W89 may be required for CBFbeta binding, we generated nine point mutants of Vif, D14A/R15A, W21A, W38A, Y40A, Y69A, G84D, E88A, W89A, and E88A/W89A. 2014 Virology Result HIV D14A;E88A;E88A;G84D;R15A;W21A;W38A;W89A;W89A;Y40A;Y69A 136;177;193;171;141;147;153;183;198;159;165 140;181;197;175;145;151;157;187;202;163;169 Vif 131 134 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Virus with DeltaVif, E88A/W89A, W21A, or W38A showed indistinguishable replication profiles to wild type in CEM-SS cells, as expected, whereas in CEM cells, showed deeply impaired replication profiles. 2014 Virology Result HIV E88A;W21A;W38A;W89A 21;32;41;26 25;36;45;30 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Virus with E88A or W89A showed comparable replication profiles to wild-type virus in both CEM-SS and CEM cells. 2014 Virology Result HIV E88A;W89A 11;19 15;23 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Virus with W89A showed intermediate and obviously impaired infectivity in the presence of A3G. 2014 Virology Result HIV W89A 11 15 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. W38A and Y69A showed intermediate results. 2014 Virology Result HIV Y69A;W38A 9;0 13;4 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Also as expected, Vif mutant, H108A was incapable of binding Cul5, however maintained its ability to bind both Elo B/C and CBF-beta (Figure 4A, lane 4). 2014 Retrovirology Result HIV H108A 30 35 Vif 18 21 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Furthermore, double mutant V25H27A was as inefficient as the H108A mutant compared to wild-type Vif. 2014 Retrovirology Result HIV H108A 61 66 Vif 96 99 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Furthermore, the N-terminal mutant Vif H27A complex was similar to the V25A complex with a binding affinity of 660 nM (Additional file 2: Figure S2). 2014 Retrovirology Result HIV H27A;V25A 39;71 43;75 Vif 35 38 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. In agreement with our prior observation that His28 was unimportant for Vif-Cul5 formation, the Vif-H28A mutant along with Vif-R23A were both capable of inducing A3G and A3F degradation similarly to wild-type Vif (Figure 2A, 2B). 2014 Retrovirology Result HIV H28A;R23A 99;126 103;130 Vif;Vif;Vif;Vif 71;95;122;208 74;98;125;211 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Interestingly, Vif L24A and I31A, which were unable to mediate both A3G and A3F degradation, still bound Cul5 similar to wild-type Vif (Figures 3, 4A). 2014 Retrovirology Result HIV I31A;L24A 28;19 32;23 Vif;Vif 15;131 18;134 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Intriguingly, the Vif C-terminal point mutant (H108A), which is part of the reported HCCH motif, only reduced the binding affinity of Cul5 for Vif by 6-fold (Kd = 36 nM) (Figure 5A,B). 2014 Retrovirology Result HIV H108A 47 52 Vif;Vif 18;143 21;146 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. L24A and H28A) bound to Cul5 with an affinity similar to wild-type (Additional file 2: Figure S2). 2014 Retrovirology Result HIV H28A;L24A 9;0 13;4 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Next, a change from valine to alanine at position 25 in the N-terminal mutant Vif V25A complex resulted in a loss of enthalpic interactions of -3 kcal/mol, which translates to a 90-fold loss in binding affinity (Kd = 511 nM) (Figure 5A,B). 2014 Retrovirology Result HIV V25A;V25A 82;20 86;52 Vif 78 81 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Single alanine mutants, V25A, H27A, M29A, and Y30A were at least 40% less efficient compared with wild-type at restoring HIV infectivity. 2014 Retrovirology Result HIV H27A;M29A;V25A;Y30A 30;36;24;46 34;40;28;50 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Surprisingly, the CD spectra for the Vif H108A C-terminal mutant complex suggested that our control mutant is also structurally different than wild-type (Figure 6B). 2014 Retrovirology Result HIV H108A 41 46 Vif 37 40 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. The loss in enthalpic interactions were, in fact, larger for the binding to the H108A mutant (DeltaH = -4.0 kcal/mol) but because the entropy contribution was more favorable (TDeltaS = -6.1 kcal/mol) and partially compensated the loss in enthalpy, the overall binding affinity was reduced to a lesser extent than for the binding to the V25A mutant (Figure 5A,B). 2014 Retrovirology Result HIV H108A;V25A 80;336 85;340 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. To test our hypothesis, we performed ITC experiments to directly measure the affinity between recombinant Cul5 and wild-type Vif as well as N- and C- terminal mutants (V25A and H108A) complexed with CBF-beta and Elo B/C. 2014 Retrovirology Result HIV H108A;V25A 177;168 182;173 Vif 125 128 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. V25A, H27A, M29A, and Y30A) had a higher percentage of alpha helical structure and lower percentage of beta sheet structure (Figure 6B). 2014 Retrovirology Result HIV H27A;M29A;Y30A;V25A 6;12;22;0 10;16;26;4 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Vif mutants His27Ala, Met29Ala, and Tyr30Ala contributed to Vif-Cul5 interaction, in vitro, both reducing Cul5 binding by greater than 60% (Figure 1A, 1B). 2014 Retrovirology Result HIV H27A;M29A;Y30A 12;22;36 20;30;44 Vif;Vif 0;60 3;63 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Vif mutants, H27A, M29A, and Y30A, but not H28A were unable to co-precipitate endogenous Cul5, consistent with in vitro results (Figure 3). 2014 Retrovirology Result HIV H27A;H28A;M29A;Y30A 13;43;19;29 17;47;23;33 Vif 0 3 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Vif mutants, L24A, V25A, and to a lesser extent I31A also inhibited Vif's ability to degrade both A3G and A3F (Figure 2A, 2B). 2014 Retrovirology Result HIV I31A;L24A;V25A 48;13;19 52;17;23 Vif;Vif 0;68 3;71 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. In 3 patients, naturally occurring polymorphisms that may or may not have an impact on levels of drug resistance were found (mutations M36I, H69K and L89M) (Table 2). 2014 BMC infectious diseases Result HIV H69K;L89M;M36I 141;150;135 145;154;139 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. Mutation K103N conferring resistance to the NNRTIs NVP, delavirdine (DLV), EFV and etravirine (ETR) was found in one patient. 2014 BMC infectious diseases Result HIV K103N 9 14 NNRTI 44 50 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. One HIV-1 subtype C isolate with thymidine analogue mutations (M41L, L210W) was detected. 2014 BMC infectious diseases Result HIV L210W;M41L 69;63 74;67 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. Polymorphic accessory mutation to the protease inhibitor class of ARVs at codon 74 (T74S) was observed in 2 patients. 2014 BMC infectious diseases Result HIV T74S 84 88 PR 38 46 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Addition of M50I to R263K does not increase integrase strand-transfer activity. 2014 Retrovirology Result HIV M50I;R263K 12;20 16;25 IN 44 53 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Analysis of clinical isolates of INSTI-naive patients from the Stanford HIV Drug Resistance Database revealed that the M50I polymorphism was present at a frequency of 10% in subtype B integrase (Figure 1). 2014 Retrovirology Result HIV M50I 119 123 IN;INSTI 184;33 193;38 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. As a result, we wanted to determine the frequency with which the M50I polymorphism occurs in the INSTI-naive patient population. 2014 Retrovirology Result HIV M50I 65 69 INSTI 97 102 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. As previously demonstrated and confirmed here, the R263K single mutation modestly diminished HIV infectivity whilst the addition of M50I to R263K further increased this deficit (Figure 4A). 2014 Retrovirology Result HIV M50I;R263K;R263K 133;52;141 137;57;146 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Combined with our biochemical results, these data indicate that the M50I mutation does not compensate for the loss in replication fitness conferred by R263K. 2014 Retrovirology Result HIV M50I;R263K 68;151 72;156 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Furthermore, the pre-existing polymorphism L63P which emerges during treatment with PIs has been shown to be compensatory when combined with a primary resistance mutation . 2014 Retrovirology Result HIV L63P 43 47 PI 84 87 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Here, with the use of wild-type and mutant integrase proteins, we show that M50I does not compensate for the decrease in enzymatic activity associated with R263K. 2014 Retrovirology Result HIV M50I;R263K 76;156 80;161 IN 43 52 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. However, further investigation revealed that the Vmax/1/2MaxProt values of the M50I and R263K enzymes were decreased compared to WT (Figures 2C-D). 2014 Retrovirology Result HIV M50I;R263K 79;88 83;93 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In contrast, the addition of M50I to R263K decreased susceptibility to EVG (FC = 6.4 for M50I/R263K compared to 3.0 for R263K alone) and RAL (FC 5.4 compared to 4.2). 2014 Retrovirology Result HIV M50I;M50I;R263K;R263K;R263K 29;89;37;94;120 33;93;42;99;125 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In contrast, the M50I/R263K double mutant conferred only low-level resistance to RAL (FC = 3.6 fold). 2014 Retrovirology Result HIV M50I;R263K 17;22 21;27 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In these experiments, both the Vmax and Km of the M50I enzyme were comparable to those of the WT enzyme whereas R263K resulted in a decreased Vmax and increased Km (Figures 3B-D). 2014 Retrovirology Result HIV M50I;R263K 50;112 54;117 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Long-term infection studies confirmed these results although the R263K replication deficit was mostly observed early in the infection course (Figure 4B). 2014 Retrovirology Result HIV R263K 65 70 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. M50I alone did not confer resistance to DTG or RAL but did confer low-level resistance to EVG (FC = 5.4 fold). 2014 Retrovirology Result HIV M50I 0 4 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. M50I does not compensate for the reduction in HIV replication associated with R263K. 2014 Retrovirology Result HIV R263K;M50I 78;0 83;4 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Occurrence of the M50I polymorphism in treatment-naive individuals living with HIV-1 subtype B. 2014 Retrovirology Result HIV M50I 18 22 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Overall, the addition of M50I to R263K did not compensate for the decrease in enzymatic efficiency associated with the R263K mutant. 2014 Retrovirology Result HIV M50I;R263K;R263K 25;33;119 29;38;124 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Previous studies have demonstrated that the primary resistance mutation R263K decreases integrase activity in cell-free assays . 2014 Retrovirology Result HIV R263K 72 77 IN 88 97 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The addition of M50I to R263K did not compensate for the decreased Vmax/1/2MaxProt of the R263K enzyme (Figure 2D). 2014 Retrovirology Result HIV M50I;R263K;R263K 16;24;90 20;29;95 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The addition of M50I to R263K slightly increased integrase Vmax but further increased the Km, resulting in a non-significant increase in enzyme efficiency (Figure 3D). 2014 Retrovirology Result HIV M50I;R263K 16;24 20;29 IN 49 58 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The effect of M50I with R263K on susceptibility to INSTIs. 2014 Retrovirology Result HIV M50I;R263K 14;24 18;29 INSTI 51 57 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The M50I mutant alone did not negatively impact HIV replication capacity; however, the addition of M50I to R263K further decreased viral fitness. 2014 Retrovirology Result HIV M50I;M50I;R263K 4;99;107 8;103;112 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The M50I mutant enzyme was associated with low-level resistance to all INSTIs tested (FC ~ 2.5) in these cell-free assays. 2014 Retrovirology Result HIV M50I 4 8 INSTI 71 77 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The M50I polymorphism was selected in culture as a secondary mutation to R263K as well as sequenced from a patient failing treatment with RAL . 2014 Retrovirology Result HIV M50I;R263K 4;73 8;78 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The R263K mutation did not greatly affect DTG activity (FC = 2.6) and the addition of M50I did not have a significant effect on the level of resistance observed (FC = 2.8). 2014 Retrovirology Result HIV M50I;R263K 86;4 90;9 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. To determine whether M50I might impact viral replication capacity, we performed TZM-bl infection assays with varying amounts of wild-type pNL4.3, pNL4.3INB(R263K), and pNL4.3INB(M50I/R263K) viruses (Figure 4). 2014 Retrovirology Result HIV M50I;M50I;R263K;R263K 21;178;156;183 25;182;161;188 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Using TZM-bl assays with pNL4.3 M50I and R263K viruses, we also showed that the combination of M50I and R263K increased resistance to DTG (FC = 15.6 fold) compared to R263K alone (FC = 8.5 fold) (Table 2). 2014 Retrovirology Result HIV M50I;R263K;R263K;R263K 95;41;104;167 99;46;109;172 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. We therefore wanted to determine if the addition of M50I, a natural polymorphism in integrase, to R263K affected susceptibility to DTG, RAL, and EVG in strand-transfer assays. 2014 Retrovirology Result HIV M50I;R263K 52;98 56;103 IN 84 93 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. When these experiments were repeated with EVG, the R263K mutation alone conferred moderate-level resistance (FC = 21.4 fold) and, when combined with M50I, resistance to EVG was further increased (FC = 34.4 fold). 2014 Retrovirology Result HIV M50I;R263K 149;51 153;56 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. When varying the concentration of the INBWT, INBM50I, INBR263K, and INBM50I/R263K proteins (Figure 2A), the activity of the M50I mutant initially appeared to be greater than that of the WT enzyme (Figure 2B). 2014 Retrovirology Result HIV M50I;M50I;R263K 125;71;76 129;75;81 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. In addition, the D67N thymidine-analogue mutation (TAM) was observed in only two children whose mother had received prevention of HIV MTCT. 2014 Journal of the International AIDS Society Result HIV D67N 17 21 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. NNRTI resistance mutations were present in all (100%) children whose viruses harboured DRM: K103N in 43%, Y181C, K101E and V106M each in 29%; and Y188L in 14%. 2014 Journal of the International AIDS Society Result HIV K101E;K103N;V106M;Y181C;Y188L 113;92;123;106;146 118;97;128;111;151 NNRTI 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. Only one (8%) child born without chemoprophylaxis of MTCT showed virus harbouring the K101E NNRTI resistance mutation. 2014 Journal of the International AIDS Society Result HIV K101E 86 91 NNRTI 92 97 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. Only one child on a PI-based regimen (1/16, 6.3%) harbored a major protease mutation and the most common pattern for children on PI-based regimens was the M184V mutation alone (Table 4). 2014 AIDS research and therapy Result HIV M184V 155 160 PR;PI;PI 67;20;129 75;22;131 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. The Q151M complex (a multinucleoside resistance mutation) was present in two genotypes, one from a child on an NNRTI-based regimen and one from a child on a PI-based regimen. 2014 AIDS research and therapy Result HIV Q151M 4 9 NNRTI;PI 111;157 116;159 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. The most prevalent variant were the M184V mutation (n = 24), the K103N/S mutation (n = 14) and the Y181C/Y/I/V mutation (n = 8) within the reverse transcriptase genome. 2014 AIDS research and therapy Result HIV K103N;K103S;M184V;Y181C;Y181I;Y181V;Y181Y 65;65;36;99;99;99;99 72;72;41;110;110;110;110 RT 139 160 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. An even greater loss of efficacy (EC50 = 1900 nM) was observed with viruses containing the G140S/Q148H double mutant form of IN (Table 4). 2014 Journal of medicinal chemistry Result HIV G140S;Q148H 91;97 96;102 IN 125 127 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Cells infected with viruses containing either the Y143R or the N155H mutant forms of IN, showed significantly elevated EC50 values (162 nM and 154 nM, respectively). 2014 Journal of medicinal chemistry Result HIV N155H;Y143R 63;50 68;55 IN 85 87 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Compound 8c also retains good efficacy against the Y143R mutant (EC50 = 11 nM) as well as both the N155H mutant (EC50 = 31 nM; RAL has EC50 = 154 nM) and the G140S/Q148H mutant (EC50 = 308 nM) (Table 4). 2014 Journal of medicinal chemistry Result HIV G140S;N155H;Q148H;Y143R 158;99;164;51 163;104;169;56 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. For example, compound 7c exhibits single digit nanomolar antiviral potencies against both WT and the Y143R mutant, while showing a lower potency against the G140S/Q148H mutant (EC50 = 438 nM). 2014 Journal of medicinal chemistry Result HIV G140S;Q148H;Y143R 157;163;101 162;168;106 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Of particular note is the ability of 8c to maintain efficacy equivalent to that of RAL against the G118R mutant while showing approximately one order of magnitude greater efficacy than RAL against the remaining mutants in the table. 2014 Journal of medicinal chemistry Result HIV G118R 99 104 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Table 5 contains data showing the efficacy of compounds against the G118R and E138K/Q148K mutants, which have recently been identified through in vitro selection studies with second-generation inhibitors. 2014 Journal of medicinal chemistry Result HIV E138K;G118R;Q148K 78;68;84 83;73;89 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. A105T and A92E/A105T CA mutants were included in the analysis because they confer sensitivity to CsA in H9 cells. 2014 Retrovirology Result HIV A105T;A92E;A105T 15;10;0 20;14;5 Capsid 21 23 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. A105T transduction was inhibited in the 3D clone as in the parental HeLa cell line but in the 5C clone the magnitude of inhibition by CsA was reduced. 2014 Retrovirology Result HIV A105T 0 5 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. A92E replication was increased 7-fold by CsA in the human Burkitt's lymphoma derived B-cell line AKATA and in the human alveolar adenocarcinoma epithelial cell line A549. 2014 Retrovirology Result HIV A92E 0 4 Alveolar adenocarcinoma;Burkitt lymphoma 120;58 143;76 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. A92E transduction (Figure 6B) and nuclear entry (Figure 6D) were enhanced by CypA KD in AKATA cells, reproducing the phenotype seen with transduction in the presence of CsA (Figure 5). 2014 Retrovirology Result HIV A92E 0 4 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. A92E vector was more dependent on CsA in HeLa cells than in any of the other 27 cell lines tested (Figure 4). 2014 Retrovirology Result HIV A92E 0 4 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Additionally, CsA increased A92E viral 2-LTR circles in Jurkat cells to a lesser extent than it did in HeLa cells, indicating that CypA binding to CA inhibits HIV-1 nuclear entry to different extents in HeLa and Jurkat T cells. 2014 Retrovirology Result HIV A92E 28 32 LTR;Capsid 41;147 44;149 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. AKATA and MT4 cells were transduced with WT, A92E, or A105T viruses. 2014 Retrovirology Result HIV A105T;A92E 54;45 59;49 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. As a control that GFP reporter activity resulted from infection and not from passive transfer of GFP protein, target cells were also challenged with an HIV-1 vector bearing two RT mutations (D185K and D186K) that render the viral polymerase catalytically inactive (data not shown). 2014 Retrovirology Result HIV D185K;D186K 191;201 197;206 Pol;RT 230;177 240;179 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. As compared with WT CA, the recovery of A92E CA in the pellet was significantly increased (Figure 11A). 2014 Retrovirology Result HIV A92E 40 44 Capsid;Capsid 20;45 22;47 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. As controls for conditions under which CA cores have preciously characterized stabilities, each of these cell lines was transduced to express either human TRIM5 fused to human CypA (hT5Cyp) or a non-restrictive mutant that has the CA binding site in CypA disrupted (hT5Cyp-H436Q). 2014 Retrovirology Result HIV H436Q 273 278 Capsid;Capsid 39;231 41;233 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. As expected, WT and A92E viruses were restricted by hT5Cyp in HeLa clone 3D (Figure 10A) and in MT4 (Figure 10B). 2014 Retrovirology Result HIV A92E 20 24 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. As previously reported, A92E infection of HeLa and H9 cells was increased significantly when the CypA-CA interaction was disrupted (11-fold and 6-fold, respectively, Figure 4). 2014 Retrovirology Result HIV A92E 24 28 Capsid 102 104 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. CA mutant A105T therefore seems to have a dominant effect over the A92E mutation. 2014 Retrovirology Result HIV A105T;A92E 10;67 15;71 Capsid 0 2 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Combination with A92E rescued P90A transduction in both cell lines. 2014 Retrovirology Result HIV A92E;P90A 17;30 21;34 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. CsA decreased the amount of CA protein recovered in the pellet for both WT and A92E CA. 2014 Retrovirology Result HIV A92E 79 83 Capsid;Capsid 28;84 30;86 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. CsA increased the efficiency of nuclear entry, compensating for the 2-fold block in reverse transcription of WT virus, and making the A92E CA mutant 5-fold more infectious than it was under control conditions in HeLa cells. 2014 Retrovirology Result HIV A92E 134 138 RT;Capsid 84;139 105;141 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. D185K/D186K RT double mutant virus was used as a control to demonstrate that signal in the PCR reactions required de novo viral cDNA synthesis in the target cells and did not result from contaminating DNA. 2014 Retrovirology Result HIV D186K;D185K 6;0 11;5 RT 12 14 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Enhancement of A92E replication by CsA was between 2 to 4-fold in 13 cell lines tested and in the primary CD4+ T cells. 2014 Retrovirology Result HIV A92E 15 19 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Finally, CsA inhibited A92E virus transduction of the human T cell line MT4 by about 2-fold. 2014 Retrovirology Result HIV A92E 23 27 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. G89V inhibited transduction around 10-fold in both cell lines and, when combined with A92E, transduction was rescued in HeLa cells but not Jurkat. 2014 Retrovirology Result HIV A92E;G89V 86;0 90;4 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. HeLa 3D and MT4 cells were transduced with WT, A92E, and A105T capsid mutants in the presence or absence of CsA. 2014 Retrovirology Result HIV A105T;A92E 57;47 62;51 Capsid 63 69 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. HeLa and Jurkat T cells were treated with 5 muM CsA or DMSO as control, and challenged with WT, A92E, A105T or A92E/A105T CA mutant viruses (Figure 3). 2014 Retrovirology Result HIV A105T;A105T;A92E;A92E 102;116;96;111 107;121;100;115 Capsid 122 124 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. HeLa cell transduction by A92E was ~3-fold lower than by the WT, and CsA enhanced its infectivity around 11-fold (Figure 3A). 2014 Retrovirology Result HIV A92E 26 30 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. HeLa clone 3D bearing hT5Cyp-H436Q was challenged with envelope-minus HIV-1 pseudotyped with VSV G, bearing either WT or A92E CA, in the presence of CsA or DMSO as solvent control. 2014 Retrovirology Result HIV A92E;H436Q 121;29 125;34 Env;Capsid 55;126 63;128 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In contrast, disagreement exists among different labs regarding which step in the viral replication cycle is inhibited by CypA interaction with the A92E or G94D mutant CAs. 2014 Retrovirology Result HIV A92E;G94D 148;156 152;160 Capsid 168 171 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In contrast, the A92E CA mutant virus was 3-fold lower than WT CA in the control HeLa cells, while depletion of CypA increased its transduction around 10-fold. 2014 Retrovirology Result HIV A92E 17 21 Capsid;Capsid 22;63 24;65 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In contrast, the inhibition of reverse transcription by CsA did not correlate with the infectivity effects for WT CA in HeLa cells or for A92E infecting either HeLa or Jurkat T cells. 2014 Retrovirology Result HIV A92E 138 142 RT;Capsid 31;114 52;116 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In contrast, transduction of MT4 cells by WT, A92E, or A105T was inhibited by CsA. 2014 Retrovirology Result HIV A105T;A92E 55;46 60;50 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In Jurkat T cells, CypA KD had no effect on A92E virus replication. 2014 Retrovirology Result HIV A92E 44 48 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In Jurkat T cells, the A92E mutant conferred resistance to the inhibitory effect of CsA. 2014 Retrovirology Result HIV A92E 23 27 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In MT4 cells bearing hT5Cyp-H436Q the recovery of A92E CA in the pellet was similar to that of the WT CA, and CsA caused no change for either. 2014 Retrovirology Result HIV A92E;H436Q 50;28 54;33 Capsid;Capsid 55;102 57;104 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In the case of both cell lines, disruption of the CypA catalytic site in hT5Cyp (H436Q), mutation of an HIV-1 CA amino acid important for interaction with CypA (G89V), or the competitive inhibitor CsA, prevented restriction activity (Figure 10). 2014 Retrovirology Result HIV G89V;H436Q 161;81 165;86 Capsid 110 112 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In the HeLa 3D clone, CsA enhanced A92E transduction 22-fold and WT transduction 4-fold (Figure 8A). 2014 Retrovirology Result HIV A92E 35 39 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In the HeLa 5C clone, A92E transduction increased only 4-fold in the presence of CsA; WT virus infectivity was not altered. 2014 Retrovirology Result HIV A92E 22 26 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Inhibition of HIV-1 reverse transcription by CsA correlated with effects on infectivity of WT virus in Jurkat T cells and for A105T and A92E/A105T mutant viruses infecting either HeLa or Jurkat (compare Figure 3A and B). 2014 Retrovirology Result HIV A105T;A105T;A92E 126;141;136 131;146;140 RT 20 41 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Nuclear entry of the A92E virus was inhibited compared to WT virus and the CsA treatment rescued the block. 2014 Retrovirology Result HIV A92E 21 25 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. On Jurkat T cells, the A105T mutant was less infectious than the WT, but the magnitude inhibition by CsA was similar to that of the WT. 2014 Retrovirology Result HIV A105T 23 28 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Other studies, offer evidence that a dominant, CypA-dependent restriction factor is expressed in the cell lines in which replication of the A92E is CsA-dependent. 2014 Retrovirology Result HIV A92E 140 144 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. P90A inhibited transduction of Jurkat T cells, but there was no effect in HeLa. 2014 Retrovirology Result HIV P90A 0 4 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Relative to the amount of viral cDNA formed by either WT or A92E, CsA increased the levels of 2-LTR circles (Figure 3B and C). 2014 Retrovirology Result HIV A92E 60 64 LTR 96 99 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Reverse transcription of WT, A92E, or A105T viruses, in the setting of acute infection of either AKATA or MT4 cells was inhibited by CsA treatment (Figure 5B). 2014 Retrovirology Result HIV A105T;A92E 38;29 43;33 RT 0 21 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Some previous studies indicate that the cells in which CsA enhances A92E replication contain higher levels of CypA compared to cells in which CsA has no effect on A92E replication. 2014 Retrovirology Result HIV A92E;A92E 68;163 72;167 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The A105T CA mutant rendered WT and A92E viruses insensitive to the effect of CsA on the nuclear entry of the viral cDNA. 2014 Retrovirology Result HIV A105T;A92E 4;36 9;40 Capsid 10 12 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The CA A105T mutant virus replicated like the WT in HeLa cells and was inhibited 2-fold in the presence of CsA. 2014 Retrovirology Result HIV A105T 7 12 Capsid 4 6 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The CypA-CA interaction inhibited nuclear entry of the A92E CA mutant to different extents in HeLa and Jurkat T cells. 2014 Retrovirology Result HIV A92E 55 59 Capsid;Capsid 9;60 11;62 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The effect of 5 muM CsA on WT and A92E CA mutant transduction of HeLa and Jurkat T cells was tested next (Figure 1B). 2014 Retrovirology Result HIV A92E 34 38 Capsid 39 41 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The effect of CA mutants G89V and P90A was tested next (Figure 1C). 2014 Retrovirology Result HIV G89V;P90A 25;34 29;38 Capsid 14 16 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The effect of CsA on A92E transduction therefore varied over a large range in the 27 cell lines tested (Figure 4). 2014 Retrovirology Result HIV A92E 21 25 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The effect of CsA on the efficiency of reverse transcription (Figure 2A) by WT, A92E, A105T, and A92E/A105T CA mutant viruses was assessed acutely after infection of HeLa and Jurkat T cells (Figure 3B). 2014 Retrovirology Result HIV A105T;A105T;A92E;A92E 86;102;80;97 91;107;84;101 RT;Capsid 39;108 60;110 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The effect of CsA on transduction of AKATA cells was similar to that in HeLa cells: WT virus was insensitive to CsA, A92E infectivity was enhanced, while infectivity of A105T was inhibited. 2014 Retrovirology Result HIV A105T;A92E 169;117 174;121 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The efficiency of reverse transcription (Figure 8B) and of 2-LTR circle formation (Figure 8C), after challenge of the 3D and 5C HeLa clones with WT, A92E, and A105T vectors, was examined next. 2014 Retrovirology Result HIV A105T;A92E 159;149 164;153 RT;LTR 18;61 39;64 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The infectivity of HIV-1 bearing the CA A92E mutation was increased 11-fold in HeLa cells. 2014 Retrovirology Result HIV A92E 40 44 Capsid 37 39 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The two clones with the most extreme effects of CsA on A92E transduction, 3D and 5C, were selected for further testing. 2014 Retrovirology Result HIV A92E 55 59 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The two stable KD cell lines were challenged with VSV G-pseudotyped, three-part HIV-1-GFP reporter vectors bearing either wild-type CA or the A92E CA mutation. 2014 Retrovirology Result HIV A92E 142 146 Capsid;Capsid 132;147 134;149 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The variable permissivity of target cells cloned by limiting dilution was exploited next to obtain 32 HeLa cell clones in which the stimulation of A92E transduction by CsA ranged from 4 to 22-fold (Figure 7). 2014 Retrovirology Result HIV A92E 147 151 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. This analysis clearly shows that P90A and G89V CA mutations have pleiotropic effects, inhibiting HIV-1 transduction to a greater extent than simple disruption of the CypA/CA interaction. 2014 Retrovirology Result HIV G89V;P90A 42;33 46;37 Capsid;Capsid 47;171 49;173 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Though the A105T mutation prevents CypA-mediated nuclear entry inhibition without blocking the CypA/CA interaction, this CA mutant still requires CypA for optimal reverse transcription. 2014 Retrovirology Result HIV A105T 11 16 RT;Capsid;Capsid 163;100;121 184;102;123 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. To assess the in vivo stability of WT and A92E CA cores after acute infection in the presence of CsA, HeLa clone 3D and MT4 cells were used as target cells. 2014 Retrovirology Result HIV A92E 42 46 Capsid 47 49 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. To confirm that the effect of CsA on A92E nuclear entry resulted from CypA blockade, endogenous CypA protein was depleted from AKATA to nearly undetectable levels using the lentiviral miRNA vectors (Figure 6A). 2014 Retrovirology Result HIV A92E 37 41 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. To determine whether increased amounts of CypA protein correlates with the effects of CsA on A92E infectivity, CypA protein levels were analyzed by western blot in 3 cell lines where A92E transduction is highly stimulated by CsA (HeLa, AKATA, and A549), 3 cell lines where A92E transduction is moderately enhanced (TE671, Jurkat T and W132 cells), and 2 cell lines where A92E is inhibited by CsA (BL41 and MT4). 2014 Retrovirology Result HIV A92E;A92E;A92E;A92E 93;183;273;371 97;187;277;375 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. To further examine the effect of CsA on A92E transduction, 27 cell lines and primary CD4+ T cells were treated with 5 muM CsA, or DMSO as control, and challenged with the three-part HIV-1 vector bearing the A92E mutation (Figure 4). 2014 Retrovirology Result HIV A92E;A92E 40;207 44;211 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. When combined in cis, the A105T mutant rescued infectivity of the A92E mutant virus in HeLa cells, but conferred sensitivity to CsA. 2014 Retrovirology Result HIV A105T;A92E 26;66 31;70 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. At week 30, RT-SHIV from two animals (33741 and 33753) had one nonsynonymous (NS) mutation each in NC: RT-SHIV from high VL animal 33741 had the A431V substitution (amino acids numbered from Gag start site); virus from moderate VL animal 33753 contained a mixture of both wild-type and P390L in the NC (data not shown). 2014 PloS one Result HIV A431V;P390L 145;286 150;291 Gag;NC;NC;RT;RT 191;99;299;12;103 194;101;301;14;105 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. At week 30, the G196R RT mutation was present in RT-SHIV from 4 of the 6 animals with detectable virus load (Table 2). 2014 PloS one Result HIV G196R 16 21 RT;RT 22;49 24;51 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Few substitutions were observed in Tat at week 30: two high VL isolates (33731 and 33810) had the S82P substitution in Tat; the two other high VL isolates contained the A121E (33741) or R106Q (33917) Tat substitutions; moderate VL isolate 33753 had two substitutions in Tat: E24K and A25V (data not shown). 2014 PloS one Result HIV A121E;A25V;E24K;R106Q;S82P 169;284;275;186;98 174;288;279;191;102 Tat;Tat;Tat;Tat 35;119;200;270 38;122;203;273 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G196R was present in infectious RT-SHIV isolated from PBMC co-cultivations from 3 of these animals and 2 of the 7 animals had virus with K275R in RT (Table 2). 2014 PloS one Result HIV K275R;G196R 137;0 142;5 RT;RT 32;146 34;148 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. High VL animals had RT-SHIV with the following RT mutations: either L74V or V75L, which resulted in RT with tandemly repeated leucine or valine at residues 74 and 75 (4 of 4 animals); G196R (3 of 4 animals); L214F (3 of 4 animals); K275R (2 of 4 animals); M357T (1 of 4 animals) or M357R (1 of 4 animals); and Q507H (2 of 4 animals). 2014 PloS one Result HIV G196R;K275R;L214F;L74V;M357R;M357T;Q507H;V75L 184;232;208;68;282;256;310;76 189;237;213;72;287;261;315;80 RT;RT;RT 20;47;100 22;49;102 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. However, the G196R mutation was detected as a minor component (5.0%) of the RT-SHIV inoculum following 454 deep sequencing (1,900X sequencing depth). 2014 PloS one Result HIV G196R 13 18 RT 76 78 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. In addition, there was no reversion upon three rounds of serial passage of the RT-SHIV mutants (G196R, K275R or the G196R, K275R double mutant) in CEMx174 (data not shown). 2014 PloS one Result HIV G196R;G196R;K275R;K275R 96;116;103;123 101;121;108;128 RT 79 81 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. In one culture another RT mutation, H208L, transiently appeared during the first passage, but was not present in subsequent passages. 2014 PloS one Result HIV H208L 36 41 RT 23 25 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Interestingly, selection for the G196R mutation was not as strong in PBMC cultures from individual donor macaques. 2014 PloS one Result HIV G196R 33 38 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Mutations observed within envelope-gp120 were N146K (0.73%) and G347R (0.73%). 2014 PloS one Result HIV G347R;N146K 64;46 69;51 Env;gp120 26;35 34;40 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Mutations observed within RT were G196R (5.0%) and E204K (1.74%). 2014 PloS one Result HIV E204K;G196R 51;34 56;39 RT 26 28 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Selection of G196R Variants of RT-SHIV in Rhesus PBMC. 2014 PloS one Result HIV G196R 13 18 RT 31 33 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Sequence analyses of plasma viral RNA revealed that virus from 6 of the 7 animals contained the G196R substitution in RT. 2014 PloS one Result HIV G196R 96 101 RT 118 120 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Sequence analyses of the entire open reading frame of env at week 4 revealed 1 or 2 mutations in virus from 5 of 7 animals; 3 isolates had R751G (Table 3). 2014 PloS one Result HIV R751G 139 144 Env 54 57 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Serial passage of RT-SHIV in the human CEMx174 cell line did not result in the emergence of the G196R or K275R variants after five rounds of passage (data not shown). 2014 PloS one Result HIV G196R;K275R 96;105 101;110 RT 18 20 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The G196R mutation emerged in RT in all replicates, became the predominant sequence by the second passage, and was maintained through subsequent passages (Table 7). 2014 PloS one Result HIV G196R 4 9 RT 30 32 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The G196R mutation was not detected in any of the replicates during 5 rounds of serial passage of RT-SHIV in PBMC from another macaque (donor #4) (Table 7). 2014 PloS one Result HIV G196R 4 9 RT 98 100 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. We also evaluated replication fitness of a site-directed G196R reverse transcriptase mutant of RT-SHIV in non-mixed cultures of rhesus macaque PBMCs. 2014 PloS one Result HIV G196R 57 62 RT;RT 63;95 84;97 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Accordingly, the S119A mutant virus disfavored adenosine and preferred cytosine at position 7 (P = 7.9 x 10-4), with recognizable alterations in complementary T/G utilization at position -3. 2014 Nucleic acids research Result HIV S119A 17 22 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Analysis of IN mutant protein fractional RY signatures revealed similar preferences for RYXRY at the integration site, with the notable exception of the R231H mutant (Supplementary Figure S2). 2014 Nucleic acids research Result HIV R231H 153 158 IN 12 14 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. As the K258S mutation abrogated IN activity under all assay conditions in vitro, it was omitted from the virus study. 2014 Nucleic acids research Result HIV K258S 7 12 IN 32 34 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Because the profile of K258S IN mutant 3'-processing and DNA-strand-transfer activities mirrored those of D64A IN, K258S IN was at best minimally active (Figure 2B). 2014 Nucleic acids research Result HIV D64A;K258S;K258S 106;23;115 110;28;120 IN;IN;IN 29;111;121 31;113;123 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Both the 3'-processing and DNA-strand-transfer activities of N232R IN were reduced ~2-fold from the WT, whereas mutants D229R and K258E were more defective, supporting between ~5 and 25% of the levels of WT IN activity (Figure 2B). 2014 Nucleic acids research Result HIV D229R;K258E;N232R 120;130;61 125;135;66 IN;IN 67;207 69;209 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Compared to the WT, S119A IN additionally favored adenosine and disfavored cytosine at position 6 (P = 1.6 x 10-4). 2014 Nucleic acids research Result HIV S119A 20 25 IN 26 28 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Compared to the WT, the R231H mutant preferred adenosine and guanosine at positions 0 and 4, respectively, as well as guanosine at position 7. 2014 Nucleic acids research Result HIV R231H 24 29 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Due to their relatively low levels of strand transfer activity (Figures 2 and 3), IN mutants D229R and K258S were omitted from this analysis. 2014 Nucleic acids research Result HIV D229R;K258S 93;103 98;108 IN 82 84 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Each tested mutation significantly reduced HIV-1 infectivity, with the extent of the infection defect ranging from ~25% for the S119A IN mutant virus to >100-fold for the N120E and K258E mutant viruses (Figure 6). 2014 Nucleic acids research Result HIV K258E;N120E;S119A 181;171;128 186;176;133 IN 134 136 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. IN containing the D64A active-site mutation was expressed and purified for use as a negative control in enzyme activity assays. 2014 Nucleic acids research Result HIV D64A 18 22 IN 0 2 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. In contrast, S119T IN supported the WT level of the IN 3'-processing and DNA-strand-transfer activities. 2014 Nucleic acids research Result HIV S119T 13 18 IN;IN 19;52 21;54 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. In contrast, the nucleotide sequence preferences of S230N, R231Q, R231S, N232R and K258E INs did not differ significantly from the WT (Figure 4 and Supplementary Figure S1). 2014 Nucleic acids research Result HIV K258E;N232R;R231Q;R231S;S230N 83;73;59;66;52 88;78;64;71;57 IN 89 92 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. IN mutant S119A yielded the largest alterations from the WT, in this case significantly increasing the RY frequency at bins -3 and 6 (Supplementary Figure S2C). 2014 Nucleic acids research Result HIV S119A 10 15 IN 0 2 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Integration site sequences were determined for the WT virus and five mutant viruses (S119A/T, N120A and R231H/S) that supported at least 10% of the levels of WT infectivity and integration (Figure 6 and Supplementary Figure S3). 2014 Nucleic acids research Result HIV N120A;R231H;R231S;S119A;S119T 94;104;104;85;85 99;111;111;92;92 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. LEDGF/p75-dependent integration reactions were scaled up 30- to 90-fold (for the minimally active K258E mutant), and linear DNA products isolated from agarose gels were ligated to a kanamycin resistance cassette as previously described. 2014 Nucleic acids research Result HIV K258E 98 103 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Most of the mutant enzymes yielded 5-bp duplications at frequencies similar to the WT, with notable exceptions of S119A and S119T INs. 2014 Nucleic acids research Result HIV S119A;S119T 114;124 119;129 IN 130 133 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. N120A IN revealed a bias for thymidine at position 6 (P = 0.003), while N120E IN displayed a marginal preference for guanosine at position 4 (P = 0.04). 2014 Nucleic acids research Result HIV N120E;N120A 72;0 77;5 IN;IN 6;78 8;80 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. One other Arg231 mutant protein, R231Q, also revealed a significant fluctuation from the WT signature, with a novel switch in preference for RY sequences at bin positions -2 and 5 outside of the central RYXRY motif. 2014 Nucleic acids research Result HIV R231Q 33 38 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. S119A and S119T IN each selected for novel nucleotides at position 7: S119A IN preferred cytosine over adenosine (P = 2.5 x 10-8) whereas S119T IN preferred thymidine with a bias against guanosine (P = 1.3 x 10-10). 2014 Nucleic acids research Result HIV S119A;S119T;S119T;S119A 70;10;138;0 75;15;143;5 IN;IN;IN 16;76;144 18;78;146 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The following mutations were engineered into a bacterial expression vector to assess effects on recombinant HIV-1 IN enzyme activity and integration site sequence preferences in vitro: S119A, S119T, N120A, N120E, D229R, S230N, R231E, R231H, R231Q, R231S, N232R, K258E and K258S. 2014 Nucleic acids research Result HIV D229R;K258E;K258S;N120A;N120E;N232R;R231E;R231H;R231Q;R231S;S119A;S119T;S230N 213;262;272;199;206;255;227;234;241;248;185;192;220 218;267;277;204;211;260;232;239;246;253;190;197;225 IN 114 116 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The N120A mutant virus revealed marginal preferences for adenosine and cytosine at positions 0 and 3, respectively. 2014 Nucleic acids research Result HIV N120A 4 9 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The N120A mutation, like R231H, significantly reduced the frequency of RY at central bin positions 0 and 3, yet in this case the bin 0 and 3 RY frequency remained greatest across the integration site (Supplementary Figure S2B). 2014 Nucleic acids research Result HIV N120A;R231H 4;25 9;30 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The R231S IN mutant viral integration preference in large part mirrored the WT pattern, with a marginal shift at position 4 toward unbiased frequencies of A/C utilization (P = 0.02; Supplementary Figure S4). 2014 Nucleic acids research Result HIV R231S 4 9 IN 10 12 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The S119A IN mutant virus also disfavored guanosine at position 9 and favored adenosine at position 0. 2014 Nucleic acids research Result HIV S119A 4 9 IN 10 12 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The S119T IN mutant virus behaved quite similar to its purified enzyme counterpart, in that similar novel base preferences were selected at positions -3 and 7 (compare Figures 4 and 7). 2014 Nucleic acids research Result HIV S119T 4 9 IN 10 12 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The total number of sequences that contained two vDNA ends varied from a low of 60 for K258E IN to a high of 170 for the R231S mutant (Table 1). 2014 Nucleic acids research Result HIV K258E;R231S 87;121 92;126 IN 93 95 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Two of the mutant enzymes with changes in the loop region between CTD beta1 and beta2, R231E and R231H, also displayed modest preferences for guanosine at position 4 (P-value differences of 0.013 and 0.04 versus the WT, respectively). 2014 Nucleic acids research Result HIV R231E;R231H 87;97 92;102 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Whereas numerous additional INs, including S119A, N120A, N120E, S230N, R231E, R231H, R231Q and R231S, also supported the WT level of 3'-processing activity, each mutant displayed between a 20% and 80% reduction in DNA-strand-transfer activity. 2014 Nucleic acids research Result HIV N120A;N120E;R231E;R231H;R231Q;R231S;S119A;S230N 50;57;71;78;85;95;43;64 55;62;76;83;90;100;48;69 IN 28 31 24520823 Human protein Staufen-2 promotes HIV-1 proliferation by positively regulating RNA export activity of viral protein Rev. Based on these predictions, hStau-2Mut with mutations Q314R, A318F and K319E was generated. 2014 Retrovirology Result HIV A318F;K319E;Q314R 61;71;54 66;76;59 24520823 Human protein Staufen-2 promotes HIV-1 proliferation by positively regulating RNA export activity of viral protein Rev. It was observed that mutations, Q314R, A318F and K319E, did not obliterate the Rev-hStau-2 interactions completely, though made it defective for Rev binding (Figure 6B). 2014 Retrovirology Result HIV A318F;K319E;Q314R 39;49;32 44;54;37 Rev;Rev 79;145 82;148 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Among the protease inhibitor-resistant viruses, eight (40%) displayed at least one darunavir resistance-associated mutation [I54M(n = 5), I50V+I84V (n = 2), I50V+I54M (n = 1)]. 2014 AIDS (London, England) Result HIV I50V;I50V;I54M;I54M;I84V 138;157;125;162;143 142;161;129;166;147 PR 10 18 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Each of the following mutations N69S, K70R, and Y115F were detected in one sample (5%). 2014 AIDS (London, England) Result HIV K70R;N69S;Y115F 38;32;48 42;36;53 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Each of the following protease inhibitor resistance mutations I50V, I82F, I84V, V62A, and L99F were detected in three samples (15%). 2014 AIDS (London, England) Result HIV I50V;I82F;I84V;L99F;V62A 62;68;74;90;80 66;72;78;94;84 PR 22 30 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Genotypic data were available for six of them, showing wild-type viruses in four cases and M184V-mutated viruses in two. 2014 AIDS (London, England) Result HIV M184V 91 96 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Integrase region was sequenced in the patient in virological failure when receiving raltegravir-based regimen, showing the major resistance mutation N155H associated with the secondary mutations E92Q and T97A. 2014 AIDS (London, England) Result HIV E92Q;N155H;T97A 195;149;204 199;154;208 IN 0 9 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Nine of the 12 patients harboring V47A-mutated viruses had previously received an indinavir-based regimen (boosted with ritonavir in five cases), and all but one were receiving lopinavir/ritonavir. 2014 AIDS (London, England) Result HIV V47A 34 38 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. The most prevalent resistance mutations to NRTI were the following: M184V (n = 17, 81%), Q151M (n = 5, 24%), S215F/Y (n = 5, 24%), V111I (n = 4, 19%), K65R (n = 3, 14%), M184I (n = 2, 10%), and D67N (n = 2, 10%). 2014 AIDS (London, England) Result HIV D67N;K65R;M184I;M184V;Q151M;S215F;S215Y;V111I 194;151;170;68;89;109;109;131 198;155;175;73;94;116;116;136 NRTI 43 47 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. The most prevalent resistance mutations to protease inhibitors were as follows: V47A (n = 12, 60%), I54M (n = 6, 30%), and L90M (n = 5, 25%. 2014 AIDS (London, England) Result HIV I54M;L90M;V47A 100;123;80 104;127;84 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. A small but statistically significant difference in 2-LTR circle formation was seen with 1.7-fold (wild type IN, p = 0.038) and 1.3-fold (D64N, p = 0.02) less circles in Nup358-/-[GFP1-1340] compared to Nup358F/F. 2014 PLoS pathogens Result HIV D64N 138 142 LTR;IN 54;109 57;111 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. As Figure 4E shows, the mutant virus behaved similarly to wild type HIV-1 in the presence and absence of full length Nup358, suggesting that whether or not HIV-1 utilizes the alternative nuclear import pathway that has been hypothesized for the N74D mutant virus and FIV, the presence of the Cyp and SUMO domains in Nup358 is not highly consequential. 2014 PLoS pathogens Result HIV N74D 245 249 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Figure 5B shows that the WT virus is strongly dependent on TNPO3 in Nup358F/F and Nup358-/-[GFP1-1340] cells but the N74D virus is not. 2014 PLoS pathogens Result HIV N74D 117 121 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Finally, as noted above, TRIMNup358Cyp inhibits both WT and N74D HIV-1. 2014 PLoS pathogens Result HIV N74D 60 64 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. For the lentiviruses, there was moderate infection impairment after acute Nup358 depletion whether the virus capsid protein can (HIV-1) or cannot (SIVmac, HIV-1 P90A, G89A, G89V) bind the Nup358 CHD. 2014 PLoS pathogens Result HIV G89A;G89V 167;173 171;177 Capsid 109 115 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. However, in these healthy Nup358-deficient human CD4+ T cells there was no significant inhibition of HIV-1, N74D HIV-1, FIV or MLV (Figure 8C,F). 2014 PLoS pathogens Result HIV N74D 108 112 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Indeed we confirmed the inhibitory effect of Nup358 knockdown in these cells, as well as resistance of the N74D capsid-mutant virus (Figure 7A,B). 2014 PLoS pathogens Result HIV N74D 107 111 Capsid 112 118 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Infections with normalized inputs showed that CypA binding mutant HIV-1 (G89A) had reduced infectivity compared to wild type HIV-1 in the parental and knocked down cells (Figure S9). 2014 PLoS pathogens Result HIV G89A 73 77 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Lastly, we assessed N74D CA mutant virus. 2014 PLoS pathogens Result HIV N74D 20 24 Capsid 25 27 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. N74D virus infection was equivalently inhibited in the Nup358 null state (Figure 1F), but also rescued by GFP1-1340. 2014 PLoS pathogens Result HIV N74D 0 4 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. The cell lines were challenged with WT and N74D reporter viruses. 2014 PLoS pathogens Result HIV N74D 43 47 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. These WT and G89V viruses were inhibited ten- and six-fold respectively by acute Nup358 gene inactivation but this was prevented if the 1-1340 N-terminal amino acid fragment was pre-expressed (Figure 1I). 2014 PLoS pathogens Result HIV G89V 13 17 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. To assess nuclear import of viral DNA, 2-LTR circle formation was determined with an integration-competent virus and with an integrase catalytic center mutant virus (D64N). 2014 PLoS pathogens Result HIV D64N 166 170 IN;LTR 125;41 134;44 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. We also assessed N74D CA mutant virus in Nup358 null cells. 2014 PLoS pathogens Result HIV N74D 17 21 Capsid 22 24 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. We also infected cells with HIV-1 capsid mutant G89V, which is defective for CypA binding. 2014 PLoS pathogens Result HIV G89V 48 52 Capsid 34 40 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. We challenged cells over a range of viral inputs with this virus, HIV-1, HIV-1 cyclophilin binding mutant capsid viruses (P90A, G89A, G89V), as well as FIV, EIAV and MLV (Figure 9B). 2014 PLoS pathogens Result HIV G89A;G89V;P90A 128;134;122 132;138;126 Capsid 106 112 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. A71T and A71V mutation rates were 14.9% and 11.2%, respectively. 2014 PloS one Result HIV A71V;A71T 9;0 13;4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. All samples with both A71V and K103N mutations had scattered distribution. 2014 PloS one Result HIV A71V;K103N 22;31 26;36 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Among mutations associated with NNRTI resistance, A98G accounted for 1.9%, and decreased the NVP and EFV sensitivity. 2014 PloS one Result HIV A98G 50 54 NNRTI 32 37 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. D67N accounted for 2.8% and caused AZT and d4T resistance. 2014 PloS one Result HIV D67N 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. G190A accounted for 1.9%, and caused high level resistance to NVP and intermediate resistance to EFV. 2014 PloS one Result HIV G190A 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. HNHIV113 site mutations included A71T, M41L, M184V, L210W, T215Y, K103N, and Y181C. 2014 PloS one Result HIV A71T;K103N;L210W;M184V;M41L;T215Y;Y181C 33;66;52;45;39;59;77 37;71;57;50;43;64;82 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. HNHIV3, HNHIV50, and HNHIV139 were clustered together, and had L10I mutation. 2014 PloS one Result HIV L10I 63 67 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. HNHIV46, HNHIV74, HNHIV77, and HNHIV137 were clustered together, with HNHIV46 and HNHIV137 having A71V, D67N, K101E, and G190A mutations, HNHIV74 having A71T mutation, and HNHIV77 having A71V and K103N mutations. 2014 PloS one Result HIV A71T;A71V;A71V;D67N;G190A;K101E;K103N 153;98;187;104;121;110;196 157;102;191;108;126;115;201 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. HNHIV97 locus mutations included D67N, T69A, K70R, T215Y, K219E, K103N, and Y181C. 2014 PloS one Result HIV D67N;K103N;K219E;K70R;T215Y;T69A;Y181C 33;65;58;45;51;39;76 37;70;63;49;56;43;81 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. In addition, there were some other mutation sites: I62V 24.3%, T12A/K/P/S 19.6%, R41K 15.9%, N37D/S 11.2%, I64L/M/V 10.3%, R57K 10.3%. 2014 PloS one Result HIV I62V;I64L;I64M;I64V;N37D;N37S;R41K;R57K;T12A;T12K;T12P;T12S 51;107;107;107;93;93;81;123;63;63;63;63 55;115;115;115;99;99;85;127;73;73;73;73 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. In PI minor resistance-associated mutations, L10I accounted for 4.7%, which is slightly lower than the rate (5%-10%) of untreated population in the Stanford HIV drug resistance database annotation. 2014 PloS one Result HIV L10I 45 49 PI 3 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. In samples with A71T mutation, HNHIV6, HNHIV58, and HNHIV149 were clustered together, HNHIV4, HNHIV83, HNHIV100, and HNHIV121 were clustered together, and HNHIV10 and HNHIV74 had scattered distribution. 2014 PloS one Result HIV A71T 16 20 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. In samples with A71V mutation, HNHIV23, HNHIV44, HNHIV63, and HNHIV114 had scattered distribution. 2014 PloS one Result HIV A71V 16 20 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. In samples with L10I mutation, HNHIV24 was not clustered together with HNHIV3, HNHIV50 and HNHIV139. 2014 PloS one Result HIV L10I 16 20 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. In seven cases Y181C occurred together with K103N, causing high resistance to EFV and NVP, and intermediate resistance to ETR and RPV. 2014 PloS one Result HIV K103N;Y181C 44;15 49;20 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. In the RT region, among mutations associated with NRTI resistance, M41L often occurred together with T215Y, which caused high resistance to AZT and d4T, and low resistance to DDI, ABC and TDF. 2014 PloS one Result HIV M41L;T215Y 67;101 71;106 NRTI;RT 50;7 54;9 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K101E and G190A caused high resistance to NVP, intermediate resistance to EFV, and low resistance to ETR and RPV. 2014 PloS one Result HIV G190A;K101E 10;0 15;5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K103N accounted for 12.1%, and caused high-level resistance to NVP and EFV. 2014 PloS one Result HIV K103N 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K103R and V179D mutations reduced NVP and EFV susceptibilities by about 10-fold. 2014 PloS one Result HIV V179D;K103R 10;0 15;5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K219E accounted for 2.8%, and could decrease AZT sensitivity in the presence of K70R or T215Y/F. 2014 PloS one Result HIV K70R;T215F;T215Y;K219E 80;88;88;0 84;95;95;5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. L210W was often associated with M41L and T215Y mutations, and caused all NRTIs except 3TC and FTC resistance. 2014 PloS one Result HIV M41L;T215Y;L210W 32;41;0 36;46;5 NRTI 73 78 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. M184L was a rare mutation, which accounted for 0.9%. 2014 PloS one Result HIV M184L 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. M184V accounted for 1.9%, and was responsible for high resistance to 3TC and FTC, and low-level resistance to ddI and ABC. 2014 PloS one Result HIV M184V 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Other mutation sites included: I293V 45.8%, V245E/G/I/K/M/L/Q/T 28.0%, R211E/G/M/K 26.2%, F214I 14.0%, K122E 14.0%, A272G/P/S 13.1%, Q207E/H/K 11.2%. 2014 PloS one Result HIV A272G;A272P;A272S;F214I;I293V;K122E;Q207E;Q207H;Q207K;R211E;R211G;R211K;R211M;V245E;V245G;V245I;V245K;V245L;V245M;V245Q;V245T 116;116;116;90;31;103;133;133;133;71;71;71;71;44;44;44;44;44;44;44;44 125;125;125;95;36;108;142;142;142;82;82;82;82;63;63;63;63;63;63;63;63 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Q58E led to TPV/r potential low-level resistance, with a resistance rate of 1.9% (2/107). 2014 PloS one Result HIV Q58E 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Samples HNHIV26, HNHIV56, and HNHIV145 were clustered together, with HNHIV26 having mutations L10I, A71T, K103N, and Y181C, and HNHIV56 and HNHIV145 having mutation A71T. 2014 PloS one Result HIV A71T;A71T;K103N;L10I;Y181C 100;165;106;94;117 104;169;111;98;122 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Samples HNHIV4, HNHIV83, HNHIV100, and HNHIV121 were clustered together, and had A71T mutation. 2014 PloS one Result HIV A71T 81 85 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Samples HNHIV6, HNHIV58, and HNHIV149 were clustered together, and had A71T mutation. 2014 PloS one Result HIV A71T 71 75 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Samples HNHIV68, HNHIV69, and HNHIV114 were clustered together, with both HNHIV68 and HNHIV69 having mutations K103N and Y181C, HNHIV114 having mutation A71V. 2014 PloS one Result HIV A71V;K103N;Y181C 153;111;121 157;116;126 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Single point mutation M184V led to high resistance to 3TC and FTC, low drug resistance to ABC, and potential low resistance to DDI; T215Y caused intermediate resistance to AZT and D4T, and low resistance to ABC, DDI and TDF; M184L did not cause resistance to NRTI. 2014 PloS one Result HIV M184L;M184V;T215Y 225;22;132 230;27;137 NRTI 259 263 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T69A and T69N accounted for 0.9% and 1.9%, respectively. 2014 PloS one Result HIV T69N;T69A 9;0 13;4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. The drug resistance mutation loci included A71V, D67H, T69N, K70R, T215F, K219E, A98G, V179D, and Y181C, with HNHIV97 and HNHIV113 clustered together. 2014 PloS one Result HIV A71V;A98G;D67H;K219E;K70R;T215F;T69N;V179D;Y181C 43;81;49;74;61;67;55;87;98 47;85;53;79;65;72;59;92;103 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. The mutation positions were A71T, L10I, A71V, and Q58E, with A71T and L10I happening simultaneously, leading to NFV potential low resistance. 2014 PloS one Result HIV A71T;A71T;A71V;L10I;L10I;Q58E 28;61;40;34;70;50 32;65;44;38;74;54 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. The mutations of both K103N and V108I caused high resistance to EFV and NVP. 2014 PloS one Result HIV K103N;V108I 22;32 27;37 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. The sites with mutation rates higher than 60.0% included: I135A/L/M/R/T/V 93.5% (100/107), among which I135V was 80.4% (86/107); T200A/E/I/P/V 89.7% (96/107), among which T200A was 81.3% (87/107); Q278E/K/N/T 88.8% (95/107), among which Q278E was 85.0% (91/107); S162C/Y 82.2% (88/107), among which S162C was 81.3% (87/107); K277R/S 66.4% (71/107), among which K277R was 64.5% (69/107). 2014 PloS one Result HIV I135A;I135L;I135M;I135R;I135T;I135V;I135V;K277R;K277R;K277S;Q278E;Q278E;Q278K;Q278N;Q278T;S162C;S162C;S162Y;T200A;T200A;T200E;T200I;T200P;T200V 58;58;58;58;58;58;103;325;361;325;197;237;197;197;197;263;299;263;129;171;129;129;129;129 73;73;73;73;73;73;108;332;366;332;208;242;208;208;208;270;304;270;142;176;142;142;142;142 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. The sites with mutation rates higher than 60.0% included: L63A/P/S/T 89.7% (96/107), among which L63P was 70.1% (75/107); V77I 82.2% (88/107); I72E/M/K/T/V 80.4% (86/107), among which I72V was 63.6% (75/107); I93L 75.7%; E35D 72.9%. 2014 PloS one Result HIV E35D;I72E;I72K;I72M;I72T;I72V;I72V;I93L;L63A;L63P;L63P;L63S;L63T;V77I 221;143;143;143;143;143;184;209;58;58;97;58;58;122 225;155;155;155;155;155;188;213;68;68;101;68;68;126 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. V108I accounted for 1.9%, and reduced NVP and EFV susceptibility. 2014 PloS one Result HIV V108I 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. V179D/E reduced NVP and EFV susceptibility by about 2-fold. 2014 PloS one Result HIV V179D;V179E 0;0 7;7 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. V179E did not cause resistance to NNRTI. 2014 PloS one Result HIV V179E 0 5 NNRTI 34 39 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. When comparing HNHIV97 and HNHIV93, T215F was replaced by T215Y, which changed intermediate resistance to DDI to low resistance. 2014 PloS one Result HIV T215F;T215Y 36;58 41;63 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Y181C accounted for 8.4%, and caused high-level resistance to NVP. 2014 PloS one Result HIV Y181C 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Y181C caused intermediate resistance to ETR and RPV. 2014 PloS one Result HIV Y181C 0 5 24603872 Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy. The only raltegravir-resistant MV detected was an E138K mutation detected at a frequency of 0.15% in one participant by Illumina sequencing, but not by 454. 2014 PloS one Result HIV E138K 50 55 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. According to phenotypic conservation analysis, the L5F and Q7E mutations were within the conserved regions, while D29V, P39S, K43R, Q61E, E65D, C67F, P79L, T91V and Q92G/K were within semi-conserved regions. 2014 BMC bioinformatics Result HIV C67F;D29V;E65D;K43R;L5F;P39S;P79L;Q61E;Q7E;Q92G;Q92K;T91V 144;114;138;126;51;120;150;132;59;165;165;156 148;118;142;130;54;124;154;136;62;171;171;160 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. According to the IAS-USA, the mutations associated with drug resistance, with a p >10%, were L10I, M36I, I62V, L63P, I64V, A71V/T, V77I, L90M, and I93L. 2014 BMC bioinformatics Result HIV A71T;A71V;I62V;I64V;I93L;L10I;L63P;L90M;M36I;V77I 123;123;105;117;147;93;111;137;99;131 129;129;109;121;151;97;115;141;103;135 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Although the study of mutations in this position has been limited to L63P to assess the effect of mutations that provide non-hydrophobic characteristics, alternative mechanisms could be shown by which HIV-1 PR compensates for pharmacological stressors. 2014 BMC bioinformatics Result HIV L63P 69 73 PR 207 209 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Codon 90 contained a drug resistance mutation (L90M) common for most PIs, with the exception of DRV and TPV, while T91 and Q92 contained the T91V, Q92G, and Q92K mutations, which are classified in the literature as unusual mutations. 2014 BMC bioinformatics Result HIV L90M;Q92G;Q92K;T91V 47;147;157;141 51;151;161;145 PI 69 72 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Figure 5 shows the overlapping structures of the wild-type PR [PDB: 1GNO] and the D29V mutant, with high similarity between both structures, as well as a difference in the location of the mutation site (position 29). 2014 BMC bioinformatics Result HIV D29V 82 86 PR 59 61 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. In the HIVdb, W6R and I72R are unusual mutations with a frequency <0.05% that only emerge after multiple major and minor resistance mutations. 2014 BMC bioinformatics Result HIV I72R;W6R 22;14 26;17 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. In the present study, among the functional groups found at position 63 (L63G, L63S, L63H and L63R), only glycine had hydrophobic characteristics, while serine was hydrophilic, and histidine and arginine were alkaline. 2014 BMC bioinformatics Result HIV L63G;L63H;L63R;L63S 72;84;93;78 76;88;97;82 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Of the 14 mutations, only L63A and H69Y were found in drug resistance positions, and T12A/I, I15V, E35D, N37D/E, R57K, K70E and I72V were contiguous to positions associated with resistance. 2014 BMC bioinformatics Result HIV E35D;H69Y;I15V;I72V;K70E;L63A;N37D;N37E;R57K;T12A;T12I 99;35;93;128;119;26;105;105;113;85;85 103;39;97;132;123;30;111;111;117;91;91 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Of the emerging mutations, D29V appears to favour resistance in silico in seven of nine PIs. 2014 BMC bioinformatics Result HIV D29V 27 31 PI 88 91 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Such differences can be observed when measuring the distance between the functional groups of the wild-type, resistant and D29V mutant PRs docked to DRV and TPV (Figure 6). 2014 BMC bioinformatics Result HIV D29V 123 127 PR 135 138 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The codons T12, N37, L63, H69, K70 and I72 include mutations weakly associated with PI resistance (T12A/I, N37D/E, L63A, H69Y, K70E, and I72R), and mutations lacking evidence of PI resistance (T12P/S, N37S/T/C/H/I, L63S/V/R/G/H, H69Q, K70R/T/I, and I72V/T/E/M). 2014 BMC bioinformatics Result HIV H69Q;H69Y;I72E;I72M;I72R;I72T;I72V;K70E;K70I;K70R;K70T;L63A;L63G;L63H;L63R;L63S;L63V;N37C;N37D;N37E;N37H;N37I;N37S;N37T;T12A;T12I;T12P;T12S 229;121;249;249;137;249;249;127;235;235;235;115;215;215;215;215;215;201;107;107;201;201;201;201;99;99;193;193 233;125;259;259;141;259;259;131;243;243;243;119;227;227;227;227;227;213;113;113;213;213;213;213;105;105;199;199 PI;PI 84;178 86;180 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The complex formed by the D29V mutant showed considerable differences between the distance of the V29 and D30 Calpha -atoms and the heteroatoms closest to the PIs (Table 4). 2014 BMC bioinformatics Result HIV D29V 26 30 PI 159 162 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The D29V and P79L mutations are located near the active site of the protease, and therefore possibly contribute to the generation of PI resistance. 2014 BMC bioinformatics Result HIV D29V;P79L 4;13 8;17 PR;PI 68;133 76;135 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The I13V (17.33%), E35D (18.21%), R41K (19%) and R57K (17.88%) mutations had a p >= 10% and were located in polymorphic positions observed in non-B subtypes. 2014 BMC bioinformatics Result HIV E35D;I13V;R41K;R57K 19;4;34;49 23;8;38;53 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The L63P mutation has a compensatory effect that increases catalytic activity from 110% to 530%; when L63P is associated with M46I, it forms a combination that is resistant to APV, IDV, LPV or NFV. 2014 BMC bioinformatics Result HIV L63P;L63P;M46I 4;102;126 8;106;130 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The prevalence of the L90M, T91V, Q92G, and Q92K mutations was 12.0, 3.33, 2.03 and 2.03%, respectively. 2014 BMC bioinformatics Result HIV L90M;Q92G;Q92K;T91V 22;34;44;28 26;38;48;32 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The PRs with L5F, D29V, L63G, L63H, L63R, L63S, and P79L mutations had lower or equal free energy of binding to ATV, LPV, NFV and TPV, than those with wild-type or drug-resistant PRs. 2014 BMC bioinformatics Result HIV D29V;L5F;L63G;L63H;L63R;L63S;P79L 18;13;24;30;36;42;52 22;16;28;34;40;46;56 PR;PR 4;179 7;182 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The T12P/S, K14R, G17D/E, Q18H, L19I/V/T, G68E, H69Q and K70R/T/I mutations were within the variable regions, and N37S/T/C/H/I, L63S/V/R/G/H, I72V/T/E/M and I93F were in highly variable regions. 2014 BMC bioinformatics Result HIV G17D;G17E;G68E;H69Q;I72E;I72M;I72T;I72V;I93F;K14R;K70I;K70R;K70T;L19I;L19T;L19V;L63G;L63H;L63R;L63S;L63V;N37C;N37H;N37I;N37S;N37T;Q18H;T12P;T12S 18;18;42;48;142;142;142;142;157;12;57;57;57;32;32;32;128;128;128;128;128;114;114;114;114;114;26;4;4 24;24;46;52;152;152;152;152;161;16;65;65;65;40;40;40;140;140;140;140;140;126;126;126;126;126;30;10;10 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. We found a high prevalence (89%) of L63PGHRS mutations in HIV-1 variants isolated from Mexican individuals, probably because of the prevalence of HIV-1 subtype B. 2014 BMC bioinformatics Result HIV L63G;L63H;L63P;L63R;L63S 36;36;36;36;36 44;44;44;44;44 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. We modelled the proteins with unusual mutations (L5F, D29V, L63G, L63R, P79L and T91V), natural polymorphisms (L63H andL63S), and drug-resistant mutant PRs with single mutations or patterns of mutations (D30N, V32I, M36I, M46I, I47V, G48V, I50V, I50L, I54M, Q58E, T74P, L76V, V82A, V82L, N83D, N88S, I84V, and L90M). 2014 BMC bioinformatics Result HIV D29V;D30N;G48V;I47V;I50L;I50V;I54M;I84V;L5F;L63G;L63H;L63R;L76V;L90M;M36I;M46I;N83D;N88S;P79L;Q58E;T74P;T91V;V32I;V82A;V82L 54;204;234;228;246;240;252;300;49;60;111;66;270;310;216;222;288;294;72;258;264;81;210;276;282 58;208;238;232;250;244;256;304;52;64;116;70;274;314;220;226;292;298;76;262;268;85;214;280;286 PR 152 155 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. However, in the case of etravirine, K65R, Y115F and the presence of TAMs were associated with increased susceptibility, whilst N348I was associated with decreased susceptibility. 2014 The Journal of antimicrobial chemotherapy Result HIV K65R;N348I;Y115F 36;127;42 40;132;47 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. Individual mutations observed were G190AS (n = 8; 47%), Y181CV (n = 6; 35%), K101I (n = 3; 18%), A98G (n = 2; 12%), K103N (n = 2; 12%) and V108I (n = 1; 6%). 2014 The Journal of antimicrobial chemotherapy Result HIV A98G;G190A;G190S;K101I;K103N;V108I;Y181C;Y181V 97;35;35;77;116;139;56;56 101;41;41;82;121;144;62;62 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. Lamivudine is omitted since almost all samples (30/35 cABC and 16/17 cNVP) showed very high-level resistance (median FC 62) due to the M184V mutation. 2014 The Journal of antimicrobial chemotherapy Result HIV M184V 135 140 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. The strength of the univariate effect of the K65R mutation was substantially reduced by the confounding effect of the presence of TAMs or the N348I mutation. 2014 The Journal of antimicrobial chemotherapy Result HIV K65R;N348I 45;142 49;147 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. There was no trend between the number of TAMs and etravirine FC, and the significant effect of M184V observed in the univariate analysis was lost after adjusting for the effect of the other mutations. 2014 The Journal of antimicrobial chemotherapy Result HIV M184V 95 100 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Cell-type-dependent Phenotype of the A92E Mutant. 2014 PloS one Result HIV A92E 37 41 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Cells were transduced with VSV-G-pseudotyped HIV-GFP-A92E mutant particles in the presence or absence of CsA sixteen hours after plating. 2014 PloS one Result HIV A92E 53 57 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. For the assays, HeLa cells were chosen because the A92E mutant demonstrated the strongest enhancement by CsA in this cell type. 2014 PloS one Result HIV A92E 51 55 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. However, depletion of nine genes including TLL1, AGMAT, NEDD9, PRSS21, IFITM1, PLEKHG1, SLC16A6, ICAM1 and ACSL5 resulted in 1.6-2.7-fold enhancement of A92E infectivity in the absence of CsA and 1.4-2.0-fold decrease in CsA enhancement of A92E infection. 2014 PloS one Result HIV A92E;A92E 153;240 157;244 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. In addition to H9 cells, we employed another T cell line, CEM, in which CsA enhanced A92E infection by 1.8-fold (Table 1). 2014 PloS one Result HIV A92E 85 89 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. In contrast to the non-permissive cell lines, we observed that CsA exhibited minimal effects on infection by the A92E mutant in HOS and 293T cells. 2014 PloS one Result HIV A92E 113 117 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. In order to identify other cell types in which infection by the A92E mutant is dependent on CsA, we tested several cell lines for VSV-G-pseudotyped-A92E infectivity in the presence or absence of CsA. 2014 PloS one Result HIV A92E;A92E 64;148 68;152 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Previously, several studies have demonstrated CsA-dependence of the A92E mutant in HeLa and H9 cells. 2014 PloS one Result HIV A92E 68 72 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. This list was further scrutinized based on two criteria: (1) Expression of a gene in HeLa cells should be higher than in any of the permissive cell types because A92E demonstrated the most pronounced CsA-dependent phenotype in HeLa cells; and (2) Expression of a gene in any of the permissive cell types should be lower than in at least two of the non-permissive cell types. 2014 PloS one Result HIV A92E 162 166 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. To identify genes that may play a role in the CypA-dependent restriction of the A92E mutant, we performed Human Gene Array analysis of the six cell lines in triplicate. 2014 PloS one Result HIV A92E 80 84 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. To test if expression of any of the selected candidate genes is necessary for the observed CsA-dependent phenotype of the A92E mutant, each of these genes was individually knocked down in HeLa cells using SMARTpool siRNAs. 2014 PloS one Result HIV A92E 122 126 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Using these two criteria, 26 genes (Table 2) were selected for analysis of their effects on HIV-1-A92E infection. 2014 PloS one Result HIV A92E 98 102 HIV infections 92 112 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. We reasoned that depletion of the restriction factor would result in enhancement of HIV-1-A92E infection in the absence of CsA, and would have minimal effects on infection in the presence of CsA, resulting in a net reduction in the extent to which CsA enhances infection of the virus. 2014 PloS one Result HIV A92E 90 94 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Also, the M16 mutant, which contained an MG insertion and an S11R mutation, was non-infectious. 2014 PloS one Result HIV S11R 61 65 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Finally, we assessed whether IG or MG insertion, combined with S11R mutation (RMG), will exert the same influence on viral infectivity in the context of other subtype C and CRF07_BC envelope gene backbones. 2014 PloS one Result HIV S11R 63 67 Env 182 190 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. In subtype B, compared with R5 V3 sequences (n = 594), the signature pattern of X4 viruses (n = 41) contained Arginine (R), Threonine (T) and Glutamine (Q) substitutions at positions 11, 22 and 25 respectively. 2014 PloS one Result HIV Q11Q 139 186 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. In subtype C, compared with the R5 V3 sequences (n = 339), the V3 signature pattern of X4 viruses (n = 20) were Glycine (G), Valine (V), Arginine (R), and Alanine (A) substitutions at positions 5, 12, 16 and 25 respectively, and also contained an insertion of two amino acids (IG) between positions 13 and 14. 2014 PloS one Result HIV A5A 152 196 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. M1 contained three mutations (S11R, A22T and D25Q), which were subtype B X4 signatures (Figure 1C(a)). 2014 PloS one Result HIV A22T;D25Q;S11R 36;45;30 40;49;34 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Mutants containing the two amino acid IG insertion between positions 13 and 14, either alone or in combination with mutations S11R, I12V, P16R, Q18R and/or D25R, were also designed (M7, M8, M9, M10, M11, M12, M13, M14 and M15). 2014 PloS one Result HIV D25R;I12V;P16R;Q18R;S11R 156;132;138;144;126 160;136;142;148;130 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Notably, additional mutations were also introduced unintentionally along with these insertions, such as V12I for C3 and C4 clones, L14I for C13 clone and G13R for CH70 clones. 2014 PloS one Result HIV G13R;L14I;V12I 154;131;104 158;135;108 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Six of the dual-tropic chimeras (NL4-3/M10V3 to NL4-3/M15V3) shared the same mutations (IG insertion and P16R mutation), while another one (NL4-3/M16V3) contained MG insertion and S11R mutation. 2014 PloS one Result HIV P16R;S11R 105;180 109;184 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Subtype B X4-like mutations (S11R, A22T and D25Q) could not confer CXCR4-using characteristics to NL4-3/M1V3. 2014 PloS one Result HIV A22T;D25Q;S11R 35;44;29 39;48;33 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Therefore, IG insertion and P16R mutation or MG insertion and S11R mutation could confer CRF07_BC V3 with CXCR4-using characteristics. 2014 PloS one Result HIV P16R;S11R 28;62 32;66 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Besides these accessory mutations previously described in HIV-2, viruses from these four patients also displayed amino acid substitutions in six HIV-2 non-polymorphic sites: Q44H (n = 2), Q45H (n = 1), K71R (n = 1), K127R (n = 1), D232N (n = 1) and K236T (n = 1), all previously unreported in HIV-2. 2014 PloS one Result HIV D232N;K127R;K236T;K71R;Q44H;Q45H 231;216;249;202;174;188 236;221;254;206;178;192 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Collectively, our data revealed three distinct patterns of mutations eliciting resistance to raltegravir in HIV-2: Q148R in one patient, E92Q - T97A in two patients, and N155H - E92A/G/Q in six patients. 2014 PloS one Result HIV E92A;E92G;E92Q;E92Q;N155H;Q148R;T97A 178;178;178;137;170;115;144 186;186;186;141;175;120;148 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Fifteen amino acid substitutions occurred at non-polymorphic positions of HIV-2 wild-type: Q44H (n = 2 patients), Q45H (n = 1), K46R (n = 3), K71R (n = 1), E85K (n = 1), Q91R (n = 1), E92A/G/Q (n = 8), T97A (n = 4), K127R (n = 1), Q148R (n = 1), V151I (n = 1), N155H (n = 7), N160K (n = 2), D232N (n = 1) and K236T (n = 1). 2014 PloS one Result HIV D232N;E85K;E92A;E92G;E92Q;K127R;K236T;K46R;K71R;N155H;N160K;Q148R;Q44H;Q45H;Q91R;T97A;V151I 291;156;184;184;184;216;309;128;142;261;276;231;91;114;170;202;246 296;160;192;192;192;221;314;132;146;266;281;236;95;118;174;206;251 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Four amino acid substitutions occurred at naturally polymorphic HIV-2 positions, but were considered in our analysis because they were previously reported as resistance associated mutations in integrase sequences from RAL-treated HIV-2 patients: I84V (n = 4), A153G (n = 3), H157N/S/R (n = 1) and S163D (n = 1). 2014 PloS one Result HIV A153G;H157N;H157R;H157S;I84V;S163D 260;275;275;275;246;297 265;284;284;284;250;302 IN 193 202 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Four substitutions at non-polymorphic HIV-2 positions were also observed in these patients' genotypes at some point during RAL selective pressure: K46R (n = 3), V151I (n = 1), L242P (n = 1) and D232N (n = 1). 2014 PloS one Result HIV D232N;K46R;L242P;V151I 194;147;176;161 199;151;181;166 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. From all the substitutions here reported for the first time, and whose impact on RAL resistance is still unknown, K46R was clearly selected and maintained over time in these patients' viruses. 2014 PloS one Result HIV K46R 114 118 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In these patients, we further observed two amino acid changes that were previously described as secondary mutations in the HIV-2 IN, I84V and S163G/D, and two polymorphisms at positions previously associated with HIV-2 INSTIs resistance: H51Q, I175L/V. 2014 PloS one Result HIV H51Q;I175L;I175V;I84V;S163D;S163G 238;244;244;133;142;142 242;251;251;137;149;149 INSTI;IN 219;129 225;131 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In this last patient, we could see the initial selection of Q91R, its replacement by E92Q three months later, followed by the selection of T97A - N160K along with E92Q and the concurrent selection against mutation at position N155. 2014 PloS one Result HIV E92Q;E92Q;N160K;Q91R;T97A 85;163;146;60;139 89;167;151;64;143 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Interestingly, and unlike the above-mentioned mutations, other two IN polymorphisms showed a significant decrease in prevalence in isolates from NRTI/PI-treated patients, as compared with drug-naive patients, thus suggesting a negative association with NRTI/PI treatment: E246D (n = 11/23 vs. 2014 PloS one Result HIV E246D 272 277 NRTI;NRTI;IN;PI;PI 145;253;67;150;258 149;257;69;152;260 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Mutation Q148H, the most frequently observed in HIV-1 at this position, was not present in our dataset. 2014 PloS one Result HIV Q148H 9 14 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Of the four patients with only one post-RAL genotype, two shared the same pattern of accessory mutations, I84V - E92A - A153G (patients 2 and 5, Table 3 ); one displayed only two of these mutations, I84V - A153G (patient 3, Table 3 ), probably due to the short exposure time to RAL; and the other displayed E92Q - T97A - S163D (patient 4, Table 3 ). 2014 PloS one Result HIV A153G;A153G;E92A;E92Q;I84V;I84V;S163D;T97A 120;207;113;309;106;200;323;316 125;212;117;313;110;204;328;320 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. RAL resistance associated mutations were identified in the ten patients: one displayed the 148 pathway, seven displayed the 155 pathway, and two displayed none of the major RAL resistance mutations, but instead the E92Q - T97A motif (patients 9 and 10, Table 3 ). 2014 PloS one Result HIV E92Q;T97A 215;222 219;226 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Substitutions E92A/G/Q, T97A, Q148R, A153G and N155H have been previously associated with some level of resistance to RAL on HIV-2. 2014 PloS one Result HIV A153G;E92A;E92G;E92Q;N155H;Q148R;T97A 37;14;14;14;47;30;24 42;22;22;22;52;35;28 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Substitutions E92Q, T97A, Q148R, V151I, N155H and D232N have been previously associated with INSTIs resistance in HIV-1. 2014 PloS one Result HIV D232N;E92Q;N155H;Q148R;T97A;V151I 50;14;40;26;20;33 55;18;45;31;24;38 INSTI 93 99 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. The '148 pathway' was observed in the virus from one patient through the presence of Q148R (patient 1, Table 3 ). 2014 PloS one Result HIV Q148R 85 90 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. The HIV-1 signature mutation N155H was observed in viruses from seven patients. 2014 PloS one Result HIV N155H 29 34 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. The last patient (whose viruses selected N155H - I84V - A153G) was genotyped early in RAL failure, and we cannot exclude that that pattern of mutations will evolve to one of the previously referred patterns as the exposure time to RAL increases. 2014 PloS one Result HIV A153G;I84V;N155H 56;49;41 61;53;46 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. They all harbored the N155H mutation in association with E92Q in two cases (patients 6 and 7, Table 3 ), and with E92G in one other case (patient 8, Table 3 ). 2014 PloS one Result HIV E92G;E92Q;N155H 115;57;22 119;61;27 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Viruses from these patients also selected the I84V substitution in one case (patient 6, Table 3 ), N160K in two cases (patients 7 and 8, Table 3 ), H157N/S/R in one case (patient 6, Table 3 ), and T97A in viruses from one of the patients who selected E92Q (patient 7, Table 3 ). 2014 PloS one Result HIV E92Q;H157N;H157R;H157S;I84V;N160K;T97A 254;150;150;150;46;100;200 258;159;159;159;50;105;204 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. When analyzing each polymorphism individually, we observed that two polymorphisms showed a significant increase in prevalence in HIV-2 NRTI/PI-treated patients compared with ARV naive patients: V19M (n = 4/23 vs. 2014 PloS one Result HIV V19M 194 198 NRTI;PI 135;140 139;142 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. A K65R mutation was also detected in a slow responding patient. 2014 BMC infectious diseases Result HIV K65R 2 6 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. A total of seven patients had HIVDR mutations detectable in the baseline samples; one mutation (V90IV) confers no resistance (Id # 339). 2014 BMC infectious diseases Result HIV V90I;V90V 96;96 101;101 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. All cases of HIVDR involved at least one NNRTI mutation, with the K103N (3/9) being the most frequently observed. 2014 BMC infectious diseases Result HIV K103N 66 71 NNRTI 41 46 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. Combined NNRTI and NRTI mutations were seen in four of nine (44.4%) participants and involved M184V/I in all cases and K65R and D67G occurred in one participant in addition to the M184I mutation. 2014 BMC infectious diseases Result HIV D67G;K65R;M184I;M184I;M184V 128;119;94;180;94 132;123;101;185;101 NNRTI;NRTI 9;19 14;23 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. However, one participant (Id # 25) had a mutation (A98G) that confers resistance to nevirapine. 2014 BMC infectious diseases Result HIV A98G 51 55 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. The K103N/X was the most common mutation observed. 2014 BMC infectious diseases Result HIV K103N;K103X 4;4 11;11 24729604 HIV-1 drug mutations in children from northern Tanzania. Another interesting finding was a strain with the Y181C mutation in a sample collected from a child born to an HIV-1-infected mother; the mother and child were not kept on any ART regimen, though they were enrolled with the antenatal services. 2014 The Journal of antimicrobial chemotherapy Result HIV Y181C 50 55 HIV infections 111 125 24729604 HIV-1 drug mutations in children from northern Tanzania. K103N (n = 4) was the second most common RT mutation and causes high-level resistance to nevirapine and efavirenz, but not to the newer NNRTIs etravirine and rilpivirine. 2014 The Journal of antimicrobial chemotherapy Result HIV K103N 0 5 NNRTI;RT 136;41 142;43 24729604 HIV-1 drug mutations in children from northern Tanzania. M184V was detected in one child who was on nevirapine single-dose syrup prophylaxis. 2014 The Journal of antimicrobial chemotherapy Result HIV M184V 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. Of concern is one virus strain with multiclass resistance: Y188L for NNRTIs and M184V for NRTIs. 2014 The Journal of antimicrobial chemotherapy Result HIV M184V;Y188L 80;59 85;64 NNRTI;NRTI 69;90 75;95 24729604 HIV-1 drug mutations in children from northern Tanzania. The most frequent RT mutation was Y181C (n = 8), which causes high-level resistance to all NNRTIs. 2014 The Journal of antimicrobial chemotherapy Result HIV Y181C 34 39 NNRTI;RT 91;18 97;20 24729604 HIV-1 drug mutations in children from northern Tanzania. We also found a case of a transitional mutation, T215S, which is detected in isolates that eventually go on to develop the NRTI drug resistance mutations T215Y and T215F. 2014 The Journal of antimicrobial chemotherapy Result HIV T215F;T215S;T215Y 164;49;154 169;54;159 NRTI 123 127 24729604 HIV-1 drug mutations in children from northern Tanzania. Y188L and G190A, which cause high-level resistance to NNRTIs, were detected in two children. 2014 The Journal of antimicrobial chemotherapy Result HIV G190A;Y188L 10;0 15;5 NNRTI 54 60 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. A similar strategy can be evaluated for inhibiting the open conformation dimer by chemically linking two DRV molecules as seen in the PRP51-D25N/DRV complex. 2014 ACS chemical biology Result HIV D25N 140 144 PR 134 136 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Additionally, "second shell" mutations L10I, L24I, L33F, and I54M alter residues that form direct interactions with residues in the active site cavity. 2014 ACS chemical biology Result HIV I54M;L10I;L24I;L33F 61;39;45;51 65;43;49;55 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Also for SQV, a second molecule was found in a location adjacent to the usual active site location in PR20/SQV and PRV32I/I47V/V82I/SQV structures. 2014 ACS chemical biology Result HIV I47V;V82I 122;127 126;135 PR;PR 102;115 104;117 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Also, as DRV interactions with PRD25N are nearly identical to those in wild-type PR/DRV complex, we resorted to using PRP51 with mutation D25N for our studies. 2014 ACS chemical biology Result HIV D25N 138 142 PR;PR;PR 31;81;118 33;83;120 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Also, the flap hinge region comprising residues 34 to 43 shares a very similar conformation in PRP51-D25N and in the ligand free conformation of PR20, which is likely due to the presence of mutations M36I and I33F in both highly drug-resistant variants. 2014 ACS chemical biology Result HIV I33F;M36I;D25N 209;200;101 213;204;105 PR;PR 95;145 97;147 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Also, the side chains of Val82 and Ile84 in wild-type PR extend closer to the aniline group of DRV compared to the good hydrophobic contacts formed by Ile82 and Val84 in PRP51-D25N/DRV. 2014 ACS chemical biology Result HIV D25N 176 180 PR;PR 54;170 56;172 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Alternate conformations were refined for 3 residues in PRP51-D25N/DRV and 7 residues in PRP51-D25N structures. 2014 ACS chemical biology Result HIV D25N;D25N 61;94 65;98 PR;PR 55;88 57;90 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Both DRV-bound and ligand-free PRP51-D25N dimers have flaps separated by a large distance between their tips. 2014 ACS chemical biology Result HIV D25N 37 41 PR 31 33 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Consequently, DRV may favor the weaker atypical binding location observed in PRP51-D25N. 2014 ACS chemical biology Result HIV D25N 83 87 PR 77 79 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Crystal Structures of Ligand-Free and DRV-Bound PRP51-D25N. 2014 ACS chemical biology Result HIV D25N 54 58 PR 48 50 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Crystals were grown of mutant PRP51-D25N in the presence of DRV, SQV, tipranavir (TPV), and amprenavir (APV) in order to identify the structural changes associated with high level resistance. 2014 ACS chemical biology Result HIV D25N 36 40 PR 30 32 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. DRV placed at the typical binding site (Figure 2A) did not fit the electron density visible in the ligand binding cavity of PRP51-D25N/DRV, and thus different locations were evaluated for the inhibitor. 2014 ACS chemical biology Result HIV D25N 130 134 PR 124 126 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Electron density for inhibitor DRV was observed within the ligand binding cavity only in the structure of PRP51-D25N/DRV. 2014 ACS chemical biology Result HIV D25N 112 116 PR 106 108 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Flaps of PRP51-D25N/DRV and PRP51-D25N Display Different Intersubunit Interactions. 2014 ACS chemical biology Result HIV D25N;D25N 34;15 38;19 PR;PR 9;28 11;30 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. For the DRV complexes, the shortest interflap distance was 8.7 A in PRP51-D25N/DRV compared with about 3.3 A for typical closed conformation dimers of PR/DRV (PDB ID 2IEN) and PR20/DRV (PDB ID 3UCB) (Supplementary Figure S2B). 2014 ACS chemical biology Result HIV D25N 74 78 PR;PR;PR 68;151;176 70;153;178 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Four mutations associated with drug resistance, V32I, M46L, V82I, and I84V, alter residues in the active site cavity where substrates and inhibitors usually bind. 2014 ACS chemical biology Result HIV I84V;M46L;V32I;V82I 70;54;48;60 74;58;52;64 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Further comparison of inhibitor interactions is limited since the crystal structures of the PRP51-D25N mutant are in the open conformation without inhibitor bound in the standard active site location. 2014 ACS chemical biology Result HIV D25N 98 102 PR 92 94 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Ile50/50' at the flap tips has intersubunit van der Waals contacts of about 4.0 A with Pro81'/81 in PRP51-D25N/DRV as observed for closed conformation inhibitor-bound dimers. 2014 ACS chemical biology Result HIV D25N 106 110 PR 100 102 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. In addition, DRV forms interactions with residues from other symmetry-related molecules of PRP51-D25N as shown in Figure 4B and Supplementary Figure S1. 2014 ACS chemical biology Result HIV D25N 97 101 PR 91 93 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. In contrast, this intersubunit contact was lost in ligand-free PRP51-D25N since the closest atoms of Ile50 and Pro81' were separated by 8.5 A. 2014 ACS chemical biology Result HIV D25N 69 73 PR 63 65 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. In PRP51-D25N, however, DRV showed a unique mode of binding within the open conformation flaps and lying almost perpendicular to the typical active site position. 2014 ACS chemical biology Result HIV D25N 9 13 PR 3 5 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. In PRP51-D25N/DRV, the I54M mutation introduced new van der Waals interactions with DRV (Figures 3C and 5), while M46L had no contacts with the ligand. 2014 ACS chemical biology Result HIV I54M;M46L;D25N 23;114;9 27;118;13 PR 3 5 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. In the crystal structure of PRP51-D25N/DRV, DRV forms two direct hydrogen bonds with the main chain amides of Gly49 and Gly50, and three water molecules mediate hydrogen bond interactions with Gly27, Asp30, and Gly27' from the crystallographic dimer. 2014 ACS chemical biology Result HIV D25N 34 38 Asp;PR 200;28 203;30 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Introducing the single mutation D25N in the wild-type enzyme, however, does not alter the binding of DRV observed in the crystal structure. 2014 ACS chemical biology Result HIV D25N 32 36 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Many van der Waals contacts were observed between PRP51-D25N and DRV with distances ranging from 3.8 to 4.2 A. 2014 ACS chemical biology Result HIV D25N 56 60 PR 50 52 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Multiple Mutations Contribute to the Structural Changes in PRP51-D25N. 2014 ACS chemical biology Result HIV D25N 65 69 PR 59 61 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Mutants PRV32I and PRI47V have altered interactions with inhibitors DRV and SQV; however, V82I in the triple mutant PRV32I/I47V/V82I bearing the active site residues of HIV-2 PR does not significantly alter direct contacts with inhibitor. 2014 ACS chemical biology Result HIV I47V;V32I;V82I;V82I 123;118;128;90 127;122;132;94 PR;PR;PR;PR 8;19;116;175 10;21;118;177 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Mutation K20R alters a residue near the protein surface showing varied interactions with other surface side chains. 2014 ACS chemical biology Result HIV K20R 9 13 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Mutation L33F introduces the large bulky Phe side chain, which maintains hydrophobic contacts of the wild-type enzyme, including contacts with mutated residues I15V, M36I substituting shorter side chains as reported for L33F in PR20. 2014 ACS chemical biology Result HIV I15V;L33F;L33F;M36I 160;9;220;166 164;13;224;170 PR 228 230 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Mutation L89M has not been analyzed previously in structures. 2014 ACS chemical biology Result HIV L89M 9 13 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Mutations L63P and K70Q also alter surface side chains that form a hydrophobic contact in the wild-type PR, which is eliminated in the mutant PRP51-D25N. 2014 ACS chemical biology Result HIV K70Q;L63P;D25N 19;10;148 23;14;152 PR;PR 104;142 106;144 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Mutations M46L and I54M alter residues in the flaps and are proposed to have small indirect effects on inhibitor binding and may alter the flap dynamics. 2014 ACS chemical biology Result HIV I54M;M46L 19;10 23;14 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. No inhibitor was visible in the PRP51-D25N structure obtained from crystals grown in the presence of SQV, APV, or TPV, consistent with the high level resistance of this mutant. 2014 ACS chemical biology Result HIV D25N 38 42 PR 32 34 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. One of the two flaps (residues 47/47' to 54/54') of the PRP51-D25N/DRV dimer is further away from the catalytic site than seen for the equivalent flap of PRP51-D25N as indicated by the distance of 5.6 A between the equivalent Calpha atoms of Ile50 in these two structures, while the other flap conformation is more similar in the two structures with 1.5 A distance between the Calpha atoms of Ile50' residues (Figure 6B). 2014 ACS chemical biology Result HIV D25N;D25N 62;160 66;164 PR;PR 56;154 58;156 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Our crystallographic and biochemical analysis has demonstrated the changes due to the individual single mutations of L24I, V32I, M46L, I54M, and I84V, as reviewed in Weber and Agniswamy. 2014 ACS chemical biology Result HIV I54M;I84V;L24I;M46L;V32I 135;145;117;129;123 139;149;121;133;127 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. PRP51-D25N bears 14 mutations (L10I, I15V, K20R, L24I, V32I, L33F, M36I, M46L, I54M, L63P, K70Q, V82I, I84V, and L89M) as well as D25N relative to the standard wild-type PR sequence. 2014 ACS chemical biology Result HIV D25N;D25N;I15V;I54M;I84V;K20R;K70Q;L10I;L24I;L33F;L63P;L89M;M36I;M46L;V32I;V82I 6;130;37;79;103;43;91;31;49;61;85;113;67;73;55;97 10;134;41;83;107;47;95;35;53;65;89;117;71;77;59;101 PR;PR 0;170 2;172 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. PRP51-D25N/DRV Exhibits Unusual Binding Conformation of DRV. 2014 ACS chemical biology Result HIV D25N 6 10 PR 0 2 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. PRP51-D25N/DRV was refined in space group P41212 with a monomer of residues numbered 1-99 in the asymmetric unit, while PRP51-D25N was refined in space group P41 and contained one dimer of residues numbered 1-99 and 1'-99' in the asymmetric unit. 2014 ACS chemical biology Result HIV D25N;D25N 6;126 10;130 PR;PR 0;120 2;122 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Several of the other substitutions in PRP51-D25N are shared by the highly resistant multiple mutant PR20, and their coordinated effects have been described previously. 2014 ACS chemical biology Result HIV D25N 44 48 PR;PR 38;100 40;102 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Superposition of the monomer of PRP51-D25N/DRV with each subunit of the ligand-free dimer gave the overall RMSD value of 0.97 and 0.41 A on Calpha atoms, respectively, with large differences in the conformation of the two flaps and 80's loops (residues 79/79' to 83/83') (Figure 6A). 2014 ACS chemical biology Result HIV D25N 38 42 PR 32 34 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The asymmetric flap conformations of ligand-free PRP51-D25N resemble those of another open conformation dimer of PR20 (PDB ID 3UHL), which had van der Waals contact between the flap tips and asymmetric flaps with 12.2 and 5.4 A intersubunit separation between Ile50/50' and Pro81'/81 (Figure 7). 2014 ACS chemical biology Result HIV D25N 55 59 PR;PR 49;113 51;115 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The changes in interactions of mutated residue L24I are similar in PRP51-D25N and the single mutant PRL24I. 2014 ACS chemical biology Result HIV L24I;D25N 47;73 51;77 PR;PR 67;100 69;102 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The crystallographic dimer of PRP51-D25N/DRV was generated for structural analysis. 2014 ACS chemical biology Result HIV D25N 36 40 PR 30 32 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The DRV molecule interacts with Ile72 and Gln61 from two different symmetry-related monomers of PRP51-D25N (Supplementary Figure S1). 2014 ACS chemical biology Result HIV D25N 102 106 PR 96 98 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The existence of DRV interactions with the symmetry-related PRP51-D25N raises the possibility that crystal lattice contacts influence the atypical binding of the inhibitor. 2014 ACS chemical biology Result HIV D25N 66 70 PR 60 62 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The flaps of PRP51-D25N/DRV dimer had a larger separation of 8.7 A between the closest atoms, while the flaps were separated by 4.4 A for PRP51-D25N. 2014 ACS chemical biology Result HIV D25N;D25N 19;144 23;148 PR;PR 13;138 15;140 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The mutated Met89 forms very similar contacts in PRP51-D25N, except for an additional van der Waals contact with the side chain of Val75. 2014 ACS chemical biology Result HIV D25N 55 59 PR 49 51 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The mutations in the flap hinge and flaps are likely to contribute to the extended flap conformations observed in PRP51-D25N and in inhibitor-free PR20 structures. 2014 ACS chemical biology Result HIV D25N 120 124 PR;PR 114;147 116;149 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The mutations of residues V32I, V82I, and I84V in the active site cavity are assumed to contribute to the poor affinity of the PRP51 mutant for inhibitors and the observed unusual binding site for DRV in PRP51-D25N (Figure 3). 2014 ACS chemical biology Result HIV I84V;V32I;V82I;D25N 42;26;32;210 46;30;36;214 PR;PR 127;204 129;206 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The optimized wild-type PR bears the mutations L33I and L63I shown to significantly restrict autoproteolysis of wild-type PR in addition to Q7K, which exists in PRP51. 2014 ACS chemical biology Result HIV L33I;L63I;Q7K 47;56;140 51;60;143 PR;PR;PR 24;122;161 26;124;163 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The PRP51-D25N variant showed 7,400-fold lower affinity for DRV, while introducing the single D25N mutation in the wild-type enzyme produced about 106-fold decreased affinity for DRV as measured by ITC with no change in the stoichiometry of binding. 2014 ACS chemical biology Result HIV D25N;D25N 94;10 98;14 PR 4 6 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The PRP51-D25N/DRV monomer shares an almost identical wide open conformation (RMSD of 0.33 A on equivalent Calpha atoms) with the wild-type PR crystallized with Mg2+ coordinated at the active site (PDB ID 2PC0). 2014 ACS chemical biology Result HIV D25N 10 14 PR;PR 4;140 6;142 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The shortest interatomic distances between the flap tips were 4.0 A in ligand-free PRP51-D25N, compared to 3.0 A in a typical open conformation of wild-type PR (PDB ID 1HHP), 7.7 A in another wild-type PR with Mg2+ coordinated at the active site (PDB ID 2PC0), and 6.0 A in ligand-free PR20 (PDB ID 3UF3). 2014 ACS chemical biology Result HIV D25N 89 93 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The two crystal structures designated PRP51-D25N/DRV and PRP51-D25N were refined with X-ray data at resolutions of 1.66 and 1.50 A and R-factors of 18.9% and 15.9%, respectively. 2014 ACS chemical biology Result HIV D25N;D25N 44;63 48;67 PR;PR 38;57 40;59 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The two molecules of DRV are related by 180 rotation and interact with each other in the binding cavity of the PRP51-D25N dimer (Figure 3B). 2014 ACS chemical biology Result HIV D25N 118 122 PR 112 114 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The two PRP51-D25N dimer structures were compared with open conformation structures of PR and PR20 as well as their DRV-bound complexes. 2014 ACS chemical biology Result HIV D25N 14 18 PR;PR;PR 8;87;94 10;89;96 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. The various flap conformations in wild-type PR (PDB ID 1HHP), ligand-free PRP51-D25N, and ligand-free PR20 are compared in Supplementary Figure S2A. 2014 ACS chemical biology Result HIV D25N 80 84 PR;PR;PR 44;74;102 46;76;104 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Therefore, the combination of D25N plus the 14 mutations in PRP51 is expected to compromise the affinity to low micromolar levels. 2014 ACS chemical biology Result HIV D25N 30 34 PR 60 62 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Therefore, the large separation (~7-12 A) between side chain atoms of Ile50 and Pro81' from the other subunit is conserved in the ligand-free dimers of the two highly resistant mutants PR20 and PRP51-D25N. 2014 ACS chemical biology Result HIV D25N 200 204 PR;PR 185;194 187;196 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. These interacting residues include mutations of V32I, I54M, V82I, and I84V from the selected P51 isolate and the D25N mutation. 2014 ACS chemical biology Result HIV D25N;I54M;I84V;V32I;V82I 113;54;70;48;60 117;58;74;52;64 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Two crystal structures were analyzed for the PRP51-D25N variant that was selected for high levels of resistance to DRV. 2014 ACS chemical biology Result HIV D25N 51 55 PR 45 47 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Unlike the mutated side chain of L10F in PR20/DRV, in which a new hydrophobic contact was formed between the side chains of Phe10 and mutated Ile82, mutated residue L10I in PRP51-D25N yields no new interactions with nearby residues. 2014 ACS chemical biology Result HIV L10F;L10I;D25N 33;165;179 37;169;183 PR;PR 41;173 43;175 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. van der Waals interactions occurred between DRV and PRP51-D25N residues Asn25, Ala28, Ile47, Gly48, Gly49, Ile50, Gly52, Phe53, Met54, Thr80, Pro81', Ile82, and Val84. 2014 ACS chemical biology Result HIV D25N 58 62 PR 52 54 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Among those randomized to placebo, 1 participant had 0.69% K65R by qMVA and 1.64% by deep sequencing. 2014 The Journal of infectious diseases Result HIV K65R 59 63 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Another subject showed minor variant M184V by both qMVA (1.26%) and 454 sequencing (2.75%). 2014 The Journal of infectious diseases Result HIV M184V 37 42 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Both FTC-resistant viruses from participants randomized to FTC/TDF were hypersusceptible to TDF and zidovudine (ZDV; M184V virus showed fold change IC50 of 0.46 and 0.36; M184I showed fold change IC50 of 0.44 and 0.22, respectively). 2014 The Journal of infectious diseases Result HIV M184I;M184V 171;117 176;122 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. By the next visit, plasma viremia had increased with nonsuppressive drug exposure (TFV-DP = 1.47 fmol/106 cells, FTC-TP = 0.073 pmol/106 cells) and M184I was evident by genotype. 2014 The Journal of infectious diseases Result HIV M184I 148 153 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Following study drug withdrawal at the SC visit, plasma viral load increased to 5.42 log10 cps/mL, and M184V waned to <0.5% within 14 weeks, remaining at background levels through 52 weeks of follow-up. 2014 The Journal of infectious diseases Result HIV M184V 103 108 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Of the seroconverters randomized to FTC/TDF, none showed minor variant mutations above the BCO at K65R or K70E. 2014 The Journal of infectious diseases Result HIV K65R;K70E 98;106 102;110 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Of these, genotypic and phenotypic resistance to FTC was seen in 2 of 2 participants randomized to FTC/TDF and 1 of 8 randomized to placebo with mutations M184V and I, with maximally increased fold change half maximal inhibitory concentration (IC50) values for FTC. 2014 The Journal of infectious diseases Result HIV M184V 155 160 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The genotype revealed mixed M184M/V, with predominance of the Mut codon (84% by qMVA, 85% by 454 sequencing), consistent with selection by FTC. 2014 The Journal of infectious diseases Result HIV M184M;M184V 28;28 35;35 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The mutation M184I remained predominant at week 15 (99.5% by qMVA, 98.1% by 454 sequencing), dropping to <0.5% by week 29, and remaining at residual levels. 2014 The Journal of infectious diseases Result HIV M184I 13 18 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The participant with acute infection who was randomized to placebo had multiclass resistance mutations M184V, T215Y, K103N, and P225H. 2014 The Journal of infectious diseases Result HIV K103N;M184V;P225H;T215Y 117;103;128;110 122;108;133;115 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The participant with minor variant M184I (0.53% by qMVA, open symbols) had undetectable plasma drug levels, and low but detectable PBMC drug levels prior to SC (FTC-TP 2.62 pmol/106 cells; TFV-DP 3.58 fmol/106 cells). 2014 The Journal of infectious diseases Result HIV M184I 35 40 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. To evaluate the diagnostic impact conferred by viral sequence polymorphisms in minor variant quantification by AS-PCR in the presence and absence of a cure-PCR, we measured mixtures of K65R (aga vs aaa for WT and Mut, respectively) at 0%, 0.5%, 1.0%, and 10% Mut in a consensus B background template, with or without 4 polymorphic bases in both discriminatory and universal primer-binding regions. 2014 The Journal of infectious diseases Result HIV K65R 185 189 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Two subjects showed the FTC-associated resistance mutation M184I at <1.0%, one by 454 sequencing exclusively (0.75%), and another by qMVA (0.53%). 2014 The Journal of infectious diseases Result HIV M184I 59 64 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Viral sequence diversity presents challenges for quantitative target sequence-based diagnostics, especially in homopolymer regions adjacent to DR codons such as subtype C K65R. 2014 The Journal of infectious diseases Result HIV K65R 171 175 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Viruses from 6 participants (3 FTC/TDF, 3 placebo) had other single nucleoside reverse-transcriptase inhibitor (NRTI; M41L), nonnucleoside reverse-transcriptase inhibitor (NNRTI; K103N/E), or protease inhibitor (PI)-selected (I85V) SDRM (Table 1). 2014 The Journal of infectious diseases Result HIV I85V;K103E;K103N;M41L 226;179;179;118 230;186;186;122 NNRTI;NRTI;PR;NNRTI;NRTI;PI 125;68;192;172;112;212 160;100;200;177;116;214 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. As shown in Table 3, Y181C+K101Q mutant showed a 2.48-, 4.37-, and 4.69-fold higher resistance to TMC-125, NVP and EFV, respectively, than Y181C alone mutant (P<0.05). 2014 PloS one Result HIV K101Q;Y181C;Y181C 27;21;139 32;26;144 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Besides K101Q and H221Y, the other three mutants I132L and T139K/R were rarely reported to associate with drug resistance. 2014 PloS one Result HIV H221Y;I132L;K101Q;T139K;T139R 18;49;8;59;59 23;54;13;66;66 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. CRF_BC strains with K103N and Y181C in RT were included as controls. 2014 PloS one Result HIV K103N;Y181C 20;30 25;35 RT 39 41 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. For example, K103N, Y181C and H221Y are three mutations formed by pairwise interactions. 2014 PloS one Result HIV H221Y;K103N;Y181C 30;13;20 35;18;25 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. For example, M184V and K103N had 12 (A98G, K101Q, K103N, I132L, R135L, T139K, T139R, Y181C, Y188L, G190A, H221Y, and L228R) and 6 (R135L, T139K, T139R, Y181C, H221Y, L228R) target mutations, respectively. 2014 PloS one Result HIV A98G;G190A;H221Y;H221Y;I132L;K101Q;K103N;K103N;L228R;L228R;M184V;R135L;R135L;T139K;T139K;T139R;T139R;Y181C;Y181C;Y188L 37;99;106;159;57;43;23;50;117;166;13;64;131;71;138;78;145;85;152;92 41;104;111;164;62;48;28;55;122;171;18;69;136;76;143;83;150;90;157;97 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. G190A+T139K also showed a higher increased (1.48- to 7.21-fold) resistance to all four NNRTIs than G190A alone mutation. 2014 PloS one Result HIV G190A;T139K;G190A 99;6;0 104;11;5 NNRTI 87 93 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. In addition to the three previously reported RTI resistance-related mutations (A98G, Y188L, and G190A), seven polymorphic mutations at seven positions (W88C, K101Q, I132L, T139K/R, H221Y and L228R) were presented in RT of CRF_BC strains isolated from the treatment-experienced patients, while they were completely absent in the RT of CRF_BC strains isolated from ART-naive patients. 2014 PloS one Result HIV A98G;G190A;H221Y;I132L;K101Q;L228R;T139K;T139R;W88C;Y188L 79;96;181;165;158;191;172;172;152;85 83;101;186;170;163;196;179;179;156;90 RT;RT;RT 45;216;328 48;218;330 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. In the network, mutations with higher frequency, such as M184V and K103N, were more likely to influence the other mutations. 2014 PloS one Result HIV K103N;M184V 67;57 72;62 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Interestingly, H221Y was associated with Y181C and/or K103N mutations. 2014 PloS one Result HIV H221Y;K103N;Y181C 15;54;41 20;59;46 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. K103N+H221Y mutations exhibited an increased (1.69- to 2.96-fold) resistance to the four NNRTIs tested (P<0.05), while K103N+K101Q mutants did not displayed a higher NNRTI-resistance than K103N alone mutant. 2014 PloS one Result HIV H221Y;K101Q;K103N;K103N;K103N 6;125;119;188;0 11;130;124;193;5 NNRTI;NNRTI 89;166 95;171 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. K103N+T139K mutant induce higher resistance to all four NNRTIs, with FC ranging from 2.00 to 14.15. 2014 PloS one Result HIV T139K;K103N 6;0 11;5 NNRTI 56 62 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Notably, T139K mutation had a significant influence on G190A, indicating a correlation between the two mutations. 2014 PloS one Result HIV G190A;T139K 55;9 60;14 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Of these mutations, A98G, T139R and L228R were solely selected by NVP, and Y181C has significantly higher frequency in NVP group than EFV group (P = 0.0012, fisher exact test). 2014 PloS one Result HIV A98G;L228R;T139R;Y181C 20;36;26;75 24;41;31;80 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Several mutations, including R135L, V179D, Y181C, M184V, K103N, were also present in the treatment-naive patients who were infected by HIV-1 CRF_BC strains, but their frequencies were significantly increased in ART-treated group (P<0.01), while R135L isn't reported to be associated with drug resistance. 2014 PloS one Result HIV K103N;M184V;R135L;R135L;V179D;Y181C 57;50;29;245;36;43 62;55;34;250;41;48 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Susceptibility to NNRTIs of HIV-1 CRF_BC strains with the newly identified in combination with the well-known Y181C, G190A or K103N mutation. 2014 PloS one Result HIV G190A;K103N;Y181C 117;126;110 122;131;115 NNRTI 18 24 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The K101Q, I132L and T139K/R mutants exhibited significant (2~28-fold) increases in resistance to all the four NNRTIs tested (P<0.05), and H221Y mutant had a moderate increase (approximately 2-fold) of resistance to these four NNRTIs (P<0.05), while the W88C, R135L and L228R mutations had no significant effect on the viral resistance to RTIs (Table 2). 2014 PloS one Result HIV H221Y;I132L;K101Q;L228R;R135L;T139K;T139R;W88C 139;11;4;270;260;21;21;254 144;16;9;275;265;28;28;258 NNRTI;NNRTI;RT 111;227;339 117;233;343 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The mutation T139K may be induced by other mutations, including K103N, Y181C, M184V and G190A, and the selection pressure ratio from G190A to T139K reach to 7. 2014 PloS one Result HIV G190A;G190A;K103N;M184V;T139K;T139K;Y181C 88;133;64;78;13;142;71 93;138;69;83;18;147;76 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The mutual influence between T139K and G190A hints that these two mutations may form as a mutation pattern to function synergistically. 2014 PloS one Result HIV G190A;T139K 39;29 44;34 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The pNL4-3 clone containing HIV-1CRF_BC pol with mutations Y181C, G190A or K103N was constructed through site-directed mutagenesis with or without the newly identified mutations in this study. 2014 PloS one Result HIV G190A;K103N;Y181C 66;75;59 71;80;64 Pol 40 43 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. We found that HIV-1 subtype B viruses with I132L and T139K/R mutations were also resistant to NNRTIs, although their resistant level is relatively lower than that of HIV-1 CRF_BC viruses with these mutations (Table 2). 2014 PloS one Result HIV I132L;T139K;T139R 43;53;53 48;60;60 NNRTI 94 100 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. We next examined the effect of the single mutation sites listed above in combination with Y181C or K103N on viral resistance to NNRTIs. 2014 PloS one Result HIV K103N;Y181C 99;90 104;95 NNRTI 128 134 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. We tested the phenotypic resistance of these combinations Y181C, G190A or K103N with different mutation sites in RT of HIV-1 CRF_BC to NNRTIs using an in vitro phenotypic assay. 2014 PloS one Result HIV G190A;K103N;Y181C 65;74;58 70;79;63 NNRTI;RT 135;113 141;115 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Y181C and H221Y, in particular, have strong mutual influence (conditional selection ratio of Y181C H221Y and H221Y Y181C was 45 and 11, respectively), suggesting that H221Y and Y181C may form combinatorial mutation patterns to synergistically resist the drug treatment. 2014 PloS one Result HIV H221Y;H221Y;H221Y;H221Y;Y181C;Y181C;Y181C;Y181C 10;99;109;167;93;115;177;0 15;104;114;172;98;120;182;5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Y181C+H221Y mutations resulted in significantly higher resistance to all four NNRTIs than Y181C alone mutation, ranging in 3.00~4.24 FC (P<0.05). 2014 PloS one Result HIV H221Y;Y181C;Y181C 6;90;0 11;95;5 NNRTI 78 84 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Among CRF02_AG sequences, a cluster (two sequences) with E138A mutation was observed (Figure 4). 2014 Journal of the International AIDS Society Result HIV E138A 57 62 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Among subtype D-infected patients, one cluster (two sequences) containing E138A and V179D (one with V179D and one E138A+V179D mutant) was found. 2014 Journal of the International AIDS Society Result HIV E138A;E138A;V179D;V179D;V179D 74;114;84;100;120 79;119;89;105;125 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Among variants potentially affecting the RPV susceptibility, the most common were V179I and V179D, which were found in 14 (46.7% of total) and 4 (13.3%) cases, respectively. 2014 Journal of the International AIDS Society Result HIV V179D;V179I 92;82 97;87 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. In one sequence, the Y318F mutation was found. 2014 Journal of the International AIDS Society Result HIV Y318F 21 26 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Of note, in the analysed sample, in six patients (2.5%) key NNRTI mutations not associated with RPV were noted, with K103N being the most common (five cases, 2.1%), including one case with a triple K101E/K103N/G190A mutation and one with K103N/P225H/K238T. 2014 Journal of the International AIDS Society Result HIV G190A;K101E;K103N;K103N;K238T;P225H;K103N 210;198;204;238;250;244;117 215;203;209;243;255;249;122 NNRTI 60 65 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Single cases (7.6% each) of K101E and Y181C were noted. 2014 Journal of the International AIDS Society Result HIV K101E;Y181C 28;38 33;43 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. The M184I mutation was not found in the analysed data set. 2014 Journal of the International AIDS Society Result HIV M184I 4 9 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. The most common were the E138A (found in nine cases, or 69.2% of the total key mutations) and E138G (found in two sequences, or 15.5%). 2014 Journal of the International AIDS Society Result HIV E138A;E138G 25;94 30;99 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. V90I was noted in 6 (20%) sequences, V189I in 4 (13.3%) and G190A in 2 (6.7%) cases (Figure 2). 2014 Journal of the International AIDS Society Result HIV G190A;V189I;V90I 60;37;0 65;42;4 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. A commercially available, thiol-reactive biotinylation reagent [MPB (Materials and Methods)] was used to label the free cysteine on E275C. 2014 Biochemistry Result HIV E275C 132 137 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. After AE21 had been reacted with E275C (Materials and Methods), the reaction mixture was analyzed using SDS-PAGE followed by Western blotting. 2014 Biochemistry Result HIV E275C 33 38 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Although previous work has shown that a double-cysteine gp120HxBc2 mutant V275C/W96C can be expressed and is functional, no such information was available for similar single-cysteine mutants of gp120. 2014 Biochemistry Result HIV V275C;W96C 74;80 79;84 gp120 194 199 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Although the results described above provide evidence that the reactive peptide triazole AE21 labels E275C, the ultimate goal will be a conjugated E275C in which the peptide occupies its "native" binding pocket and the protein adopts the same conformation adopted when the peptide binds noncovalently. 2014 Biochemistry Result HIV E275C;E275C 101;147 106;152 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. As shown in Figure 3, AE21 successfully biotinylated E275C gp120 (lane 3), as judged by the alpha-biotin signal at the gp120 molecular weight mark, while KR21 (on which the nonreactive biotinylated PT variant AE21 is based) did not show any signal (lane 2) at the same molecular weight mark. 2014 Biochemistry Result HIV E275C 53 58 gp120;gp120 59;119 64;124 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Because the major difference between KR21 and AE21 is the presence of the reactive maleimido group on the latter, and considering that noncovalent intermolecular complexes break up in the chaotropic environment of SDS-PAGE, these results provide evidence that AE21 is reactive for conjugation to E275C gp120. 2014 Biochemistry Result HIV E275C 296 301 gp120 302 307 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Because the only biotinylated components in the reaction mixture are the free AE21 peptide and the AE21-E275C covalent conjugate, and the former was removed via extensive ultrafiltration and dialysis (Materials and Methods), the major component captured on the SPR chip surface was assumed to be the conjugate (any trace amounts of noncovalent complexes are expected to be dissociated during the initial regeneration steps following D7324 injections). 2014 Biochemistry Result HIV E275C 104 109 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Biotinylation of E275C gp120 by MPB was found to occur with yields significantly lower than those for AE21 labeling of E275C (Figure 3). 2014 Biochemistry Result HIV E275C;E275C 17;119 22;124 gp120 23 28 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Both proteins bind the peptide with similar affinities, as shown by the value of the equilibrium dissociation constant obtained from the sensorgrams (KD values of 8.3 nM for WT gp120 and 6.8 nM for E275C). 2014 Biochemistry Result HIV E275C 198 203 gp120 177 182 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Considering the arguments put forward in the previous paragraphs for the required length of an N-terminal linker to connect the peptide to E275C on gp120, a short (~19 A) PEG [poly(ethylene glycol)] linker was introduced on the N-terminus of the peptide. 2014 Biochemistry Result HIV E275C 139 144 gp120 148 153 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Considering the lack of significant E275C labeling by MPB, and the thousand-fold higher reactivity of maleimide groups toward thiols in the pH range studied here, we conclude that using low excess AE21:E275C ratios would all but abrogate any non-cysteine reactions of AE21. 2014 Biochemistry Result HIV E275C 36 41 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Figure 5a shows the amount of sCD4 bound as a function of sCD4 concentration, for immobilized E275C gp120 compared to the NeutrAvidin-captured AE21-E275C covalent conjugate. 2014 Biochemistry Result HIV E275C;E275C 94;148 99;153 gp120 100 105 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. From this precedent, the finding that the AE21-E275C covalent conjugate has a reduced binding affinity for CD4bs and CD4i antibodies is expected. 2014 Biochemistry Result HIV E275C 47 52 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. In addition, the control ligand (E275C) is randomly oriented on the surface, while the covalent conjugate is oriented on the surface through binding with NeutrAvidin. 2014 Biochemistry Result HIV E275C 33 38 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. In light of our PT-gp120 complex model, the double-cysteine mutation V275C/W96C was especially interesting. 2014 Biochemistry Result HIV V275C;W96C 69;75 74;79 gp120 19 24 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. In the second stage, AE21 was reacted with E275C. 2014 Biochemistry Result HIV E275C 43 48 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Interestingly, the affinity of CD4 binding site mAb b12 for E275C is almost the same as that for WT gp120. 2014 Biochemistry Result HIV E275C 60 65 gp120 100 105 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. One drawback to the capture method used above is the uncertainty of the extent to which the NeutrAvidin capture method itself affects the affinity of various gp120 ligands for the AE21-E275C gp120 covalent conjugate. 2014 Biochemistry Result HIV E275C 185 190 gp120;gp120 158;191 163;196 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. One way to probe for these conformational characteristics is by testing the binding of various antibodies to the AE21-E275C conjugate. 2014 Biochemistry Result HIV E275C 118 123 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Overall, the results obtained indicate the successful synthesis of a reactive PT variant, AE21's selective noncovalent binding to gp120, and selective reaction with E275C gp120 to form a covalent conjugate. 2014 Biochemistry Result HIV E275C 165 170 gp120;gp120 130;171 135;176 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Proteins sCD4 (soluble receptor), mAbs17b (coreceptor surrogate/CD4-induced antibody), and b12 (CD4 binding site antibody) were used as analytes in SPR experiments with chip-immobilized WT or E275C gp120. 2014 Biochemistry Result HIV E275C 192 197 gp120 198 203 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Serial dilutions of purified E275C gp120 were passed over the surface, and the resulting sensorgrams were used to extract kinetic parameters of interaction between gp120 (WT and E275C) and PTs (Figure S3 of the Supporting Information). 2014 Biochemistry Result HIV E275C;E275C 29;178 34;183 gp120;gp120 35;164 40;169 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Similar results were obtained for 17b, showing a lack of binding to the AE21-E275C covalent conjugate (Figure 6b). 2014 Biochemistry Result HIV E275C 77 82 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The affinities of sCD4 and 17b for E275C are slightly reduced, though the latter still maintains nanomolar binding affinity for these molecules. 2014 Biochemistry Result HIV E275C 35 40 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The affinity of the E275C mutant for peptide triazoles was next assessed. 2014 Biochemistry Result HIV E275C 20 25 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The binding affinity of the AE21-E275C covalent conjugate for 17b was tested in an SPR assay similar to that described above for sCD4. 2014 Biochemistry Result HIV E275C 33 38 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The CaptAvidin-purified covalent conjugate was immobilized on the SPR chip like the E275C protein, using NHS/EDC coupling, and various concentrations of gp120 ligands were passed over the surfaces. 2014 Biochemistry Result HIV E275C 84 89 gp120 153 158 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The results show that the covalent conjugate has sCD4 affinity significantly reduced compared to that of E275C gp120. 2014 Biochemistry Result HIV E275C 105 110 gp120 111 116 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Therefore, introduction of the PEG linker at the N-terminus of the PT has only minimal effects on the potency of the peptide toward both WT and E275C gp120 proteins. 2014 Biochemistry Result HIV E275C 144 149 gp120 150 155 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. These results argue that binding of the PT to E275C gp120 significantly improves the labeling efficiency of the latter by AE21 and promotes formation of the covalent conjugate. 2014 Biochemistry Result HIV E275C 46 51 gp120 52 57 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. These results confirm that E275C recognizes PTs with an affinity similar to that of WT gp120 and can be a suitable candidate for further modifications. 2014 Biochemistry Result HIV E275C 27 32 gp120 87 92 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. These results show that the single-cysteine mutant E275C is functional for binding typical ligands of gp120. 2014 Biochemistry Result HIV E275C 51 56 gp120 102 107 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. This observation suggests that the affinity of AE21 for gp120, which is provided by its PT component, improves the chemical reactivity of the maleimide moiety, likely by localizing it close to the reactive -SH partner on the E275C gp120 surface. 2014 Biochemistry Result HIV E275C 225 230 gp120;gp120 56;231 61;236 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. This suggests that if the sequence used in the model were to be used to synthesize the reactive peptide, there would need to be a linker of at least ~18 A connecting the N-terminus of the peptide to the thiol group on E275C. 2014 Biochemistry Result HIV E275C 218 223 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. To investigate whether the E275C mutation provides any benefit for the conjugation reaction, AE21 was reacted with WT gp120 and, in parallel, with E275C. 2014 Biochemistry Result HIV E275C;E275C 27;147 32;152 gp120 118 123 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Together, these results demonstrate successful production of a peptide triazole-E275C covalent conjugate with interaction properties arguing that the peptide component is assembled intramolecularly with gp120. 2014 Biochemistry Result HIV E275C 80 85 gp120 203 208 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. We first tested the binding affinity of the E275C gp120 mutant for various gp120 ligands and compared it to the WT protein. 2014 Biochemistry Result HIV E275C 44 49 gp120;gp120 50;75 55;80 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. Finally, Table 3 summarizes the energetic components of the computed t-Bu to i-Pr substitution in solution, the WT protein and its Y181C variant, which is the most demanding studied here since both end points comprise bulky hydrophobic groups. 2014 Journal of chemical theory and computation Result HIV Y181C 131 136 PR 79 81 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. However, in Y181C, the computed free energy difference in the bound state ranges from 0.77 to 3.50 kcal/mol, probably due to incomplete sampling of the possible i-Pr conformations shown in Figure 4 (red line). 2014 Journal of chemical theory and computation Result HIV Y181C 12 17 PR 163 165 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. In particular, the CH2OMe analogue is more potent against the WT protein in the cell assay than predicted computationally, while the opposite is true for i-Pr against the Y181C variant. 2014 Journal of chemical theory and computation Result HIV Y181C 171 176 PR 156 158 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. In REST simulations of the WT protein, Pr is oriented exclusively away from Tyr 181, but in the Y181C variant it is observed to explore much more conformational space, including the vacancy left by Tyr 181. 2014 Journal of chemical theory and computation Result HIV Y181C 96 101 PR 39 41 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. In the context of the optimization of inhibitors of the Y181C mutant of HIV-RT, the distribution of binding poses shown in Figure 2 is particularly interesting since bulky alkyl groups that are able to occupy the space vacated by Tyr 181 are expected to be an effective means of targeting the variant form. 2014 Journal of chemical theory and computation Result HIV Y181C 56 61 RT 76 78 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. In the Y181C variant, greater gain in affinity is seen for larger hydrocarbon chains when compared with the WT, as expected, and peak binding is predicted to occur for R = isopropyl. 2014 Journal of chemical theory and computation Result HIV Y181C 7 12 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. In this respect, the greatest discrepancies (more than 1.5 kcal/mol) are in the predicted affinities of Pr for Y181C and OEt for WT. 2014 Journal of chemical theory and computation Result HIV Y181C 111 116 PR 104 106 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. Indeed, Figure 4 shows that both the i-Pr and Et analogs favor conformations that orient methyl groups toward Cys 181 in Y181C. 2014 Journal of chemical theory and computation Result HIV Y181C 121 126 PR 39 41 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. REST predicts that CH2OMe is the more potent inhibitor in the WT protein, but that OEt is more strongly favored in the Y181C variant (Table 2). 2014 Journal of chemical theory and computation Result HIV Y181C 119 124 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. The ethyl substituent is confirmed as the most potent in these assays for the WT, while, for Y181C, ethyl and isopropyl are essentially equally potent. 2014 Journal of chemical theory and computation Result HIV Y181C 93 98 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. The relative affinities of OEt and CH2OMe for the WT and Y181C variants predicted by REST are in good agreement with the experimental EC50 results, which underlines the importance of constructively occupying the space vacated by Tyr 181 when targeting the mutant protein. 2014 Journal of chemical theory and computation Result HIV Y181C 57 62 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. The situation is much improved using our REST/flip implementation, and the Y181C free energies vary over a much smaller range (1.52 to 1.79 kcal/mol). 2014 Journal of chemical theory and computation Result HIV Y181C 75 80 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. 2C, lanes 9 and 10) showed a defective interaction or completely failed to interact with CBF-beta and CUL5, as compared to WT Vif and the mutants L102S and A103S. 2014 PloS one Result HIV A103S;L102S 156;146 161;151 Vif 126 129 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. In agreement with the binding data, V85S and Q105A had only a small effect on Vif function. 2014 PloS one Result HIV Q105A;V85S 45;36 50;40 Vif 78 81 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. In order to further investigate whether differences of Vif sensitivity to A3G are caused by the different doses or mutations of Vif, we transfected HEK293T cells with NL4-3DeltaVif and A3G expression vector plus either VR1012 (as a control vector), a 2-fold higher amount of WT, or the 84/86-89, 88/89, G84D, G84A, W89A, D104A, L106S or I107S construct. 2014 PloS one Result HIV D104A;G84A;G84D;I107S;L106S;W89A 321;309;303;337;328;315 326;313;307;342;333;319 Vif;Vif 55;128 58;131 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. In repeated experiments, 84/86-89, 88/89, G84A, W89A, L106S and I107S showed a 40-90% reduction in CBF-beta and CUL5 binding when compared with WT Vif. 2014 PloS one Result HIV G84A;I107S;L106S;W89A 42;64;54;48 46;69;59;52 Vif 147 150 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. It is possible that G84D and D104A affected the binding of Vif to CUL5 but not to CBF-beta. 2014 PloS one Result HIV D104A;G84D 29;20 34;24 Vif 59 62 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. It is worth noting that G84D and D104A totally lost the ability to interact with CUL5 and showed a reduced level of interaction with CBF-beta. 2014 PloS one Result HIV D104A;G84D 33;24 38;28 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Several mutants, including 84/86-89, 88/89, G84A and W89A, all interacted with ELOB but were defective in interacting or completely failed to interact with CBF-beta and CUL5. 2014 PloS one Result HIV G84A;W89A 44;53 48;57 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. The 84/86-89, 88/89, G84D, G84A and W89A mutants in the 84GxSIEW89 region showed a reduced ability to suppress the antiviral activity of A3G, resulting in lowered virus infectivity. 2014 PloS one Result HIV G84A;G84D;W89A 27;21;36 31;25;40 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. The D104A, L106S and I107S mutations in the L102ADQLI107 region also reduced the ability of Vif to suppress the antiviral activity of A3G to different extents. 2014 PloS one Result HIV D104A;I107S;L106S 4;21;11 9;26;16 Vif 92 95 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Therefore, we transfected HEK293T cells with the negative control vector VR1012, WT Vif, G84D, W89A, D104A or I107S mutant plus A3G-V5 or A3F-V5. 2014 PloS one Result HIV D104A;G84D;I107S;W89A 101;89;110;95 106;93;115;99 Vif 84 87 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Vif mutants G84A, G84D, W89A, 84/86-89, 88/89, D104, L106S and I107S resulted in increased A3F expression and showed a reduced ability to neutralize the antiviral activity of A3F when compared to WT Vif. 2014 PloS one Result HIV G84A;G84D;I107S;L106S;W89A 12;18;63;53;24 16;22;68;58;28 Vif;Vif 0;199 3;202 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. We also examined whether the important Vif mutants G84A, G84D, 84/86-89, 88/89, W89A, D104, L106S and I107S, which all affected the interaction with CBF-beta and/or CUL5, could also affect the expression of A3F. 2014 PloS one Result HIV G84A;G84D;I107S;L106S;W89A 51;57;102;92;80 55;61;107;97;84 Vif 39 42 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. We also found that the L106S and I107S mutants. 2014 PloS one Result HIV I107S;L106S 33;23 38;28 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. We found that the 84/86-89, 88/89, G84D, G84A, W89A, D104A, L106S and I107S mutants all failed to decrease A3G expression. 2014 PloS one Result HIV D104A;G84A;G84D;I107S;L106S;W89A 53;41;35;70;60;47 58;45;39;75;65;51 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. All children were exposed to 3TC, and the majority of them (n = 316, 89.3%) harboured the M184V/I mutation (Figure 5). 2014 PloS one Result HIV M184I;M184V 90;90 97;97 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. Fourteen children (12.8%) harboured virus with reduced susceptibility to NFV/r due to the T74S polymorphism in 13 patients, and K20T in one child. 2014 PloS one Result HIV K20T;T74S 128;90 132;94 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. K65R was more common among children failing ABC-based regimens (n = 10, 12.3%) compared to the d4T-exposed group (n = 5, 1.8%, p = 0.0003). 2014 PloS one Result HIV K65R 0 4 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. Of the children without documented PI-exposure, 44 (18.0%) children showed reduced susceptibility to boosted nelfinavir (NFV/r) (Figure 4), caused by polymorphism T74S mutation in all but one child (Figure 3).This T74S mutation is a known subtype C polymorphism. 2014 PloS one Result HIV T74S;T74S 163;214 167;218 PI 35 37 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. Reduced susceptibility to NFV/r in the remaining patient was caused by N88D. 2014 PloS one Result HIV N88D 71 75 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. Resistance to ddI was commonly attributed to the L74V/I mutation (n = 44). 2014 PloS one Result HIV L74I;L74V 49;49 55;55 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The most common NNRTI mutation in this group was K103N (n = 152, 57.4%) followed by V106M (n = 105, 39.6%), P225H (n = 42, 15.8%) and V179D (n = 29, 10.9%, Figure 1). 2014 PloS one Result HIV K103N;P225H;V106M;V179D 49;108;84;134 54;113;89;139 NNRTI 16 21 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The presence of other NNRTI-mutations such as K103N (11.2%) in the non-NNRTI group indicates that non-disclosed NNRTI-exposure might have taken place in some of these patients, most likely as a result of PMTCT. 2014 PloS one Result HIV K103N 46 51 NNRTI;NNRTI;NNRTI 22;71;112 27;76;117 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The Q151M mutation was only detected in 2 ABC-exposed children (2.5%) and 6 d4T-exposed children (2.2%). 2014 PloS one Result HIV Q151M 4 9 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The Y181C mutation appeared more frequently among children without recorded NNRTI-exposure (9.0% vs 6.4%), this trend was however not statistically significant (p = 0.4728). 2014 PloS one Result HIV Y181C 4 9 NNRTI 76 81 24831260 Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. One subject had L74M, which confers potential low-level resistance to raltegravir and elvitegravir and has been found in association with major integrase resistance and as a natural polymorphism. 2015 Antiviral therapy Result HIV L74M 16 20 IN 144 153 24831260 Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. Viral polymorphisms in integrase were identified in 24 (28%) subjects, including V54I (n=1), L74I (n=7), V151I (n=3) M154I (n=2), M154L (n=2), G163E (n=1), I203M (n=2), and S230N (n=6). 2015 Antiviral therapy Result HIV G163E;I203M;L74I;M154L;S230N;V151I;V54I 143;156;93;130;173;105;81 148;161;97;135;178;110;85 IN 23 32 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. A single T124N substitution emerged after 5 passages, with KF116 concentration reaching 0.8 microM. 2014 PLoS pathogens Result HIV T124N 9 14 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. As expected (Figure S3) the A128T substitution, which is sufficient to confer resistance to BI-1001, was not observed with KF116. 2014 PLoS pathogens Result HIV A128T 28 33 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. In particular, our published crystal structures of BI-1001 bound to WT and A128T IN CCDs revealed that the A128T substitution affected the positioning of the quinoline group through the bulkier and polar threonine exerting a steric effect and electronic repulsion to BI-1001 (, also see Figure S3A). 2014 PLoS pathogens Result HIV A128T;A128T 75;107 80;112 IN 81 83 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. Indeed, our crystal structures have revealed very similar binding of KF116 to WT and A128T IN CCDs (Figure S3B). 2014 PLoS pathogens Result HIV A128T 85 90 IN 91 93 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. Moreover, KF116 potently promoted aberrant IN multimerization of A128T IN in vitro and effectively impaired A128T IN HIV-1NL4-3 replication in infected cells, whereas in control experiments the A128T IN HIV-1NL4-3 exhibited marked resistance to BI-1001 (Figure S3C). 2014 PLoS pathogens Result HIV A128T;A128T;A128T 65;108;194 70;113;199 IN;IN;IN;IN 43;71;114;200 45;73;116;202 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. The A128T IN substitution is the most prevalent mutation conferring resistance to most quinoline-based ALLINIs, including BI-1001. 2014 PLoS pathogens Result HIV A128T 4 9 IN 10 12 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. The biochemical studies showed that the A128T substitution has evolved to overcome BI-1001 induced IN multimerization rather than the inhibition of IN-LEDGF/p75 binding. 2014 PLoS pathogens Result HIV A128T 40 45 IN;IN 99;148 101;150 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. The rigid and planar quinoline scaffold of ALLINIs significantly limits its interactions with subunit 1, although its projection towards Ala-128 of subunit 1 ultimately results in marked resistance to the majority of ALLINIs through emergence of A128T substitution. 2014 PLoS pathogens Result HIV A128T 246 251 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. With further increases in KF116 concentrations, which reached 25.6 microM at passage 10, the T124N substitution within the viral pool diminished to ~3.7% and instead the triple (T124N/V165I/T174I) substitution in HIV-1 IN emerged (Figure 3A). 2014 PLoS pathogens Result HIV T124N;T174I;V165I;T124N 178;190;184;93 183;195;189;98 IN 219 221 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Furthermore, in the cleaved SOS context, absence of the I559P modification had differential effects on b6 and b12 binding: b6 bound to SOS.R6 more strongly than b12 (SOS.R6 vs. 2014 Retrovirology Result HIV I559P 56 61 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Hence, the I559P point substitution in gp41ECTO influences the CD4bs. 2014 Retrovirology Result HIV I559P 11 16 gp41 39 43 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. In contrast, the non-NAb b6 and the bNAb b12, also directed to the CD4bs but which do not neutralize the BG505.T332N pseudovirus, bound well and indistinguishably to the gp120-gp41ECTO protomer and gp120 monomer, but negligibly to the trimer (Figure 1). 2014 Retrovirology Result HIV T332N 111 116 gp41;gp120;gp120 176;170;198 180;175;203 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. In summary, the I559P change in the cleaved context and cleavage itself both markedly shield V3 epitopes, whereas in the uncleaved context SOS must be combined with the I559P change to exert a V3 masking effect. 2014 Retrovirology Result HIV I559P;I559P 16;169 21;174 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. It can be noted that although neither b6 nor b12 neutralizes the BG505.T332N pseudovirus, they have drastically different properties and modes of Env interaction in that b6 is a non-NAb and b12 a bNAb. 2014 Retrovirology Result HIV T332N 71 76 Env 146 149 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. It is therefore significant that these two epitopes, overlapping the CD4bs, are differentially affected by how gp120 is anchored to gp41ECTO, and also by the presence of the trimer-stabilizing I559P change. 2014 Retrovirology Result HIV I559P 193 198 gp41;gp120 132;111 136;116 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. It should be noted, however, that the IC50 values for neutralization of the BG505.T332N pseudovirus by the PGV04 and PGT121 Fabs were 3.5 and 1.1 nM. 2014 Retrovirology Result HIV T332N 82 87 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The CD4bs-directed bNAb VRC01, which potently neutralizes the corresponding BG505.T332N pseudovirus, bound strongly and similarly to all three antigens, with markedly slow dissociation. 2014 Retrovirology Result HIV T332N 82 87 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The I559P change in the gp140UNC context enhanced F240 binding (IP.SEKS compared with WT.SEKS, which differ only at residue-559, Figure 2). 2014 Retrovirology Result HIV I559P 4 9 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The I559P change probably impedes the formation of a six-helix bundle and thereby favors F240 binding. 2014 Retrovirology Result HIV I559P 4 9 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The I559P change therefore strongly promotes PG16 binding only when Env is cleaved. 2014 Retrovirology Result HIV I559P 4 9 Env 68 71 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The I559P mutation had a weak but definite masking effect on both the b6 and b12 epitopes when Env was uncleaved (IP.SEKS vs. 2014 Retrovirology Result HIV I559P 4 9 Env 95 98 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The IC50 for PGT145 Fab neutralization of BG505.T332N pseudovirus, 2.7 nM, was close to the K d for the Fab, 2.0 nM (and to K d1 for monovalent binding of IgG, 2.9 nM); if the measured affinity were relevant, 50% neutralization and 50% occupancy of Fab on trimer would approximately coincide (Additional file 3: Tables S3 and S6). 2014 Retrovirology Result HIV T332N 48 53 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The two V3-specific MAbs 14e and 19b, which do not neutralize BG505.T332N pseudovirus, bound strongly to the gp120 monomer but only negligibly to the trimer. 2014 Retrovirology Result HIV T332N 68 73 gp120 109 114 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. They both bound to intermediate levels with SOS.R6 and SOSIP.SEKS, indicating that the omission of the I559P change and the lack of cleavage equally increased exposure of the V3 region. 2014 Retrovirology Result HIV I559P 103 108 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. VRC01, a CD4bs bNAb that does neutralize the BG505.T332N pseudovirus, bound significantly to all six forms of Env (Figure 2), while clearly differentiating among them. 2014 Retrovirology Result HIV T332N 51 56 Env 110 113 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. We previously reported a strong correlation between NAb binding to D7324 epitope-tagged BG505 SOSIP.664 trimers in ELISA and neutralizing potency against the sequence-matched BG505.T332N pseudovirus. 2014 Retrovirology Result HIV T332N 181 186 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. We studied the binding of nine MAbs to six forms of Env: SOSIP.R6 (i.e., SOSIP.664) is the fully cleaved and stabilized form; WT.SEKS lacks both the SOSIP mutations and the cleavage site; SOSIP.SEKS lacks only the cleavage site; SOS.R6 lacks only the I559P mutation; SOS.SEKS lacks the I559P mutation and the cleavage site; IP.SEKS lacks the SOS link between gp120 and gp41ECTO as well as the cleavage site (Figure 2). 2014 Retrovirology Result HIV I559P;I559P 251;286 256;291 gp41;gp120;Env 369;359;52 373;364;55 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. When added to WT.SEKS, I559P alone had no effect, but added to SOS.SEKS it reduced binding markedly. 2014 Retrovirology Result HIV I559P 23 28 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Combination of H221Y and Y181C was detected in the 10th month of antiviral therapy with the frequency more than 30% in quasispecies. 2014 BMC infectious diseases Result HIV H221Y;Y181C 15;25 20;30 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Comparing K101Q/Y181C/H221Y with K101Q in the presence of EFV, we found the contribution of Y181C plus H221Y to resistance was 13.22-fold which was higher than the sum of the folds of K101Q/Y181C versus K101Q and K101Q/H221Y versus K101Q. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C;H221Y;H221Y;K101Q;K101Q;K101Q;K101Q;K101Q;Y181C;Y181C 22;10;16;103;219;33;184;203;213;232;92;190 27;15;21;108;224;38;189;208;218;237;97;195 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. From the 22nd month on, the frequency of H221Y/Y181C in quasispecies was 100% in plasma. 2014 BMC infectious diseases Result HIV H221Y;Y181C 41;47 46;52 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. H221Y, a novel NNRTI-resistance mutation relevant to NVP, emerged in all the six patients. 2014 BMC infectious diseases Result HIV H221Y 0 5 NNRTI 15 20 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, not until the 28th month did the frequency of H221Y/Y181C in quasispecies become 100% in PBMCs. 2014 BMC infectious diseases Result HIV H221Y;Y181C 55;61 60;66 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, the viruses, Y181C along with K101Q and H221Y, presented a little IC50 increase of the three NRTIs. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C 49;39;22 54;44;27 NRTI 102 107 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Interestingly, K101Q plus H221Y contributed to a significant 25.00-fold decrease in EFV resistance while a 4.0-fold increase in NVP resistance. 2014 BMC infectious diseases Result HIV H221Y;K101Q 26;15 31;20 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. K101Q caused 2.63-fold and 1.32-fold change of IC50 respectively (Figure 1A-B). 2014 BMC infectious diseases Result HIV K101Q 0 5 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Regarding K101Q as the background, we analyzed the interaction between Y181C and H221Y of five drugs respectively. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C 81;10;71 86;15;76 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Remarkably, K101Q was observed along with the double mutations at the early time of antiviral therapy. 2014 BMC infectious diseases Result HIV K101Q 12 17 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Table 1 displayed the FC in three NRTIs as the following: K101Q/H221Y>K101Q/Y181C/H221Y>K101Q/Y181C. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C 83;89;95 88;94;100 NRTI 35 40 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Table 1 shows viruses carrying K101Q slightly altered resistance to AZT, 3TC and d4T, and the same as K101Q/Y181C viruses. 2014 BMC infectious diseases Result HIV K101Q;K101Q;Y181C 32;103;109 37;108;114 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. The copresence of K101Q and Y181C in viruses resulted in a little increase in EFV resistance, but a 986.4-fold increase in NVP resistance. 2014 BMC infectious diseases Result HIV K101Q;Y181C 18;28 23;33 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. The interaction between Y181C and H221Y at the background of K101Q. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C 34;61;24 39;66;29 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Viruses harboring K101Q/H221Y displayed significantly resistance to AZT, 3TC and d4T (10.37-fold, 11.14-fold and 20.77-fold). 2014 BMC infectious diseases Result HIV H221Y;K101Q 24;18 29;23 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. We also analyzed the interaction between sites 181 and 221 in NRTIs at the background of K101Q. 2014 BMC infectious diseases Result HIV K101Q 89 94 NRTI 62 67 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. We guessed the interaction between Y181C and H221Y was synergetic. 2014 BMC infectious diseases Result HIV H221Y;Y181C 45;35 50;40 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. We observed viruses containing K101Q/Y181C/H221Y result in a 5.00-fold significant increase in EFV resistance and a 1253.9-fold increase in NVP resistance. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C 43;31;37 48;36;42 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. We obtained one reference virus pNL4-3 WT and 4 recombined HIV-1 viruses separately harboring K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y and K101Q. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C;H221Y;K101Q;K101Q;K101Q;Y181C 107;95;101;133;114;127;143;120 112;100;106;138;119;132;148;125 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. We speculated Y181C had significantly decreased the H221Y resistance to the three NRTIs at the background of K101Q. 2014 BMC infectious diseases Result HIV H221Y;K101Q;Y181C 52;109;14 57;114;19 NRTI 82 87 24895029 Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS. Its structure with two different X groups (Br and OMe) might be critical in influencing antiviral potency against these drug-resistant viral strains, especially for E138K and K101E, two major mutations associated with next-generation NNRTI drugs 1a and 1b. 2014 ChemMedChem Result HIV E138K;K101E 165;175 170;180 NNRTI 234 239 24895029 Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS. K101E and E138K are the most important mutations associated with resistance against new-generation NNRTI drug 1b, and A17 is a NNRTI resistant strain with double mutations of K103N and Y181C. 2014 ChemMedChem Result HIV E138K;K103N;Y181C;K101E 10;175;185;0 15;180;190;5 NNRTI;NNRTI 99;127 104;132 24895029 Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS. More interestingly, we found that 8c displayed very similar potency against two wild-type (NL4-3 and III-B) and resistant viral strains with RTMDR, K101E or E138K mutation, resulting in lower resistance fold change (RFC) values (1.1-2.1) than 1b. 2014 ChemMedChem Result HIV E138K;K101E 157;148 162;153 24895029 Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS. Subsequently, potent compounds 6a, 6g, and 8a-c were selected for further testing in parallel with 1b against wild-type viral strain IIIB and NNRTI-resistant HIV-1 mutants, including RT-multidrug-resistant (HIV-1RTMDR1), K101E, E138K, and A17 (Table 2). 2014 ChemMedChem Result HIV E138K;K101E 228;221 233;226 NNRTI;RT 142;183 147;185 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. Among all eight alanine mutants, only E314A mutant could render the YU2.6248V3 chimera to infect CCR5+ cells. 2014 PloS one Result HIV E314A 38 43 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. Both G306A and S322A mutants caused significantly more cell death than wild type ZP6248 (p<0.001) as well as YU2.6248V3 (p = 0.003). 2014 PloS one Result HIV G306A;S322A 5;15 10;20 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. Both G306A and S322A mutants only partially impaired ZP6248's ability to infect GPR15+ cells. 2014 PloS one Result HIV G306A;S322A 5;15 10;20 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. In our previous study, the E314G mutation also allowed ZP6248 to efficiently use CCR5 for entry. 2014 PloS one Result HIV E314G 27 32 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. Since both the E314G and E314A mutation could reduce the replication capacity of ZP6248 in GPR15+ cells but allowed the virus to infect CCR5+ cells, we sought to test if introduction of the rare combination of glutamic acid and lysine into the YU2 (YU2.GPEK) would allow virus to infect GPR15+ cells. 2014 PloS one Result HIV E314A;E314G 25;15 30;20 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. Six alanine mutants (V307A, E314A, K315A, V316A, Y317A and F318A) completely lost their ability to infect GPR15+ cells. 2014 PloS one Result HIV E314A;F318A;K315A;V307A;V316A;Y317A 28;59;35;21;42;49 33;64;40;26;47;54 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. The p24 concentrations in the culture of two alanine mutants (G306A and S322A) were similar but slightly lower than that of YU2.6248V3 in GPR15+ cells. 2014 PloS one Result HIV G306A;S322A 62;72 68;77 p24 4 7 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. These results suggested that the low levels of p24 detected in the culture of YU2.6248V3 as well as both G306A and S322A mutants in GPR15+ cells was partly due to the higher numbers of dead cells. 2014 PloS one Result HIV G306A;S322A 105;115 110;120 p24 47 50 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. Furthermore, S79A was unable to enhance TAK1 phosphorylation (Figure 7B). 2014 Retrovirology Result HIV S79A 13 17 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. Importantly, as opposed to increasing the phosphorylation of wild type and K34R TAK1, Vpr was unable to render the K158R and K209R mutants phosphorylated (Figure 4C). 2014 Retrovirology Result HIV K158R;K209R;K34R 115;125;75 120;130;79 Vpr 86 89 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. In addition, S79A failed to stimulate NF-kappaB- or AP-1-dependent luciferase expression (Figure 7E). 2014 Retrovirology Result HIV S79A 13 17 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. In further support of the dependence on TAK1 for Vpr to activate NF-kappaB and AP-1, we examined the effect of a Vpr mutant called S79A, known to be crucial for the function of Vpr. 2014 Retrovirology Result HIV S79A 131 135 Vpr;Vpr;Vpr 49;113;177 52;116;180 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. Next, we used the same amounts of viruses WT, DeltaVpr and S79A to infect Jurkat cells and examined the phosphorylation of TAK1. 2014 Retrovirology Result HIV S79A 59 63 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. The results of Figure 4B showed that mutations K158R and K209R, but not K34R, abrogated TAK1 polyubiquitination. 2014 Retrovirology Result HIV K158R;K209R;K34R 47;57;72 52;62;76 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. The S79A virus was unable to induce the phosphorylation of TAK1 (Figure 7D). 2014 Retrovirology Result HIV S79A 4 8 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. To further confirm this finding, we mutated sernine 79 of Vpr in the context of the pNLENY1-ES (WT) proviral DNA clone and generated pNLENY1-ES S79A. 2014 Retrovirology Result HIV S79A 144 148 Vpr 58 61 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. We found that S79A lost its interaction with TAK1 (Figure 7A). 2014 Retrovirology Result HIV S79A 14 18 24912982 Interactions with DCAF1 and DDB1 in the CRL4 E3 ubiquitin ligase are required for Vpr-mediated G2 arrest. Vpr mutants that fall into this category include Q65R and H71R. 2014 Virology journal Result HIV H71R;Q65R 58;49 62;53 Vpr 0 3 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. 2, Panel A), indicating that the vast majority of both WT and mutant N260Q gp160 were not yet processed in the Golgi apparatus. 2014 PloS one Result HIV N260Q 69 74 gp160 75 80 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. A large fraction of both WT and mutant N260Q gp160 resided in the ER, which is the organelle in which protein biosynthesis takes place. 2014 PloS one Result HIV N260Q 39 44 gp160 45 50 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. After long-term passaging of these transfected C8166 cells, two mutations occurred in the V1/V2-loop of gp120 that allowed cell-free infection (albeit still poor) of mutant HIV containing N260Q gp160. 2014 PloS one Result HIV N260Q 188 193 gp120;gp160 104;194 109;199 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Again, mutation S128N did not change the findings for N260Q gp160, whether with or without chloroquine. 2014 PloS one Result HIV N260Q;S128N 54;16 59;21 gp160 60 65 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Although the gp120 and gp41 levels in mutant N260Q gp120 virus were somewhat higher in this experiment than previously reported, its levels were still markedly lower than WT levels. 2014 PloS one Result HIV N260Q 45 50 gp120;gp120;gp41 13;51;23 18;56;27 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Although this mutation was not selected in our experiments, we aimed to confirm these observations by introducing the R302I mutation in the HIV-1 gp160 that already contained the N260Q, N260Q/V120A, N260Q/V120A/S128N and N260Q/S128N background mutations. 2014 PloS one Result HIV N260Q;S128N;V120A;N260Q;N260Q;N260Q;R302I;S128N;V120A 199;211;205;179;186;221;118;227;192 204;216;210;184;191;226;123;232;197 gp160 146 151 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. As can be seen from the Western blot analysis in Figure 2, Panel A, WT and mutant gp160 were EndoH sensitive, indicating that the majority of WT and mutant N260Q gp160 had high-mannose-type glycans and resided in the ER. 2014 PloS one Result HIV N260Q 156 161 gp160;gp160 82;162 87;167 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. As shown previously, the N260Q mutation in gp120 is associated with a much lower incorporation of gp120 and gp41 in the virus particle envelope. 2014 PloS one Result HIV N260Q 25 30 Env;gp120;gp120;gp41 135;43;98;108 143;48;103;112 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. At the end of the selection process, solely the S128N and N260Q gp120 mutations were retained in gp160. 2014 PloS one Result HIV N260Q;S128N 58;48 63;53 gp120;gp160 64;97 69;102 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Chloroquine also increased the level of N260Q/S128N gp120 on the cell surface, although less pronounced compared to the single mutant. 2014 PloS one Result HIV N260Q;S128N 40;46 45;51 gp120 52 57 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Co-staining was also seen in the Golgi apparatus for both WT and mutant N260Q gp160. 2014 PloS one Result HIV N260Q 72 77 gp160 78 83 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Despite long-term passaging (>30 passages) of the mutant N260Q/S128N gp120 virus, mutations that further increased viral infectivity did not arise. 2014 PloS one Result HIV N260Q;S128N 57;63 62;68 gp120 69 74 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Figure 3 shows that the V120A and V120A/S128N gp120 mutations were virtually unable to restore infectivity of mutant N260Q gp160 HIV-1. 2014 PloS one Result HIV N260Q;S128N;V120A;V120A 117;40;24;34 122;45;29;39 gp120;gp160 46;123 51;128 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Figure 6B, showed slightly delayed maturation of both N260Q and N260Q/S128N gp160. 2014 PloS one Result HIV N260Q;N260Q;S128N;N260Q;N260Q;S128N 55;65;71;54;64;70 60;70;76;59;69;75 gp160 76 81 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. For this purpose, C8166 cells were transfected with the HIV-1 construct encoding mutant N260Q gp160. 2014 PloS one Result HIV N260Q 88 93 gp160 94 99 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Given the fact that eventual expression of either glycoprotein on the viral envelope surface was low, we investigated the possibility that mutant N260Q gp120 and gp41 are degraded in lysosomes. 2014 PloS one Result HIV N260Q 146 151 Env;gp120;gp41 76;152;162 84;157;166 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Hence, a fraction of mutant N260Q gp160 folded properly and became CD4-binding competent but the majority failed to do so. 2014 PloS one Result HIV N260Q 28 33 gp160 34 39 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. However, mutant N260Q gp120 virus derived from chloroquine-treated cells showed an increased level of gp120, gp41, and in particular gp160, in the virus particle. 2014 PloS one Result HIV N260Q 16 21 gp120;gp120;gp160;gp41 22;102;133;109 27;107;138;113 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Introduction of the S128N mutation in the mutant N260Q gp160 virus did not increase the expression and incorporation of both gp120 and gp41 in the virus particle. 2014 PloS one Result HIV N260Q;S128N 49;20 54;25 gp120;gp160;gp41 125;55;135 130;60;139 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. It has been reported earlier that an arginine to isoleucine mutation at amino acid position 302 in gp160 restored infection potential of the mutant N260Q/S128N virus. 2014 PloS one Result HIV N260Q;R302I;S128N 148;37;154 153;95;159 gp160 99 104 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. It was shown that inhibition of lysosomal activity had a limited negative effect on the surface expression of WT gp120, while there was a marked increase in the level of surface gp120 in the case of the N260Q mutation. 2014 PloS one Result HIV N260Q 203 208 gp120;gp120 113;178 118;183 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Later on, the S128N mutation appeared in combination with V120A and N260Q. 2014 PloS one Result HIV N260Q;S128N;V120A 68;14;58 73;19;63 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Maturation of mutant N260Q gp160 and mutant N260Q/S128N gp160 is delayed versus WT gp160. 2014 PloS one Result HIV N260Q;N260Q;S128N 21;44;50 26;49;55 gp160;gp160;gp160 27;56;83 32;61;88 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Mutant N260Q gp160 was recognized much less by CD4-IgG2 than WT gp160. 2014 PloS one Result HIV N260Q 7 12 gp160;gp160 13;64 18;69 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Mutated N260Q gp160 proceeds from the endoplasmic reticulum to the Golgi. 2014 PloS one Result HIV N260Q 8 13 gp160 14 19 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Mutation in the V1/V2-loop of gp120 can only moderately compensate for the loss of infectivity due to the N260Q gp120 mutation. 2014 PloS one Result HIV N260Q 106 111 gp120;gp120 30;112 35;117 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. none of the viruses that contained the R302I mutation in combination with the N260Q or N260Q/S128N gp120 mutations showed any infectivity gain (data not shown). 2014 PloS one Result HIV N260Q;N260Q;R302I;S128N;N260Q;N260Q;R302I;S128N 79;88;40;94;78;87;39;93 84;93;45;99;83;92;44;98 gp120 99 104 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. On the other hand, the single S128N mutation in the N260Q gp160 background allowed about 7% infection at the highest dose of virus added to the uninfected C8166 cell cultures. 2014 PloS one Result HIV N260Q;S128N 52;30 57;35 gp160 58 63 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Only a minority of ER-lumenal mutant N260Q gp160 and N260Q/S128N gp160 is CD4-binding competent. 2014 PloS one Result HIV N260Q;N260Q;S128N 37;53;59 42;58;64 gp160;gp160 43;65 48;70 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Previous attempts by site-directed mutagenesis to introduce new glycosylation sites in the proximity of the 260NGS262 glycosylation motif failed to restore the infectivity of the N260Q gp120 mutant virus. 2014 PloS one Result HIV N260Q 179 184 gp120 185 190 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Since the compensatory mutation S128N did not improve overall oxidative folding of gp160 we wondered whether it affected CD4 binding. 2014 PloS one Result HIV S128N 32 37 gp160 83 88 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Since the S128N mutation partially restored viral infectivity, we wondered whether this was caused by increased incorporation of gp120 and gp41 in the virus particle. 2014 PloS one Result HIV S128N 10 15 gp120;gp41 129;139 134;143 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The compensatory mutation hence did not markedly affect oxidative folding of N260Q gp160. 2014 PloS one Result HIV N260Q 77 82 gp160 83 88 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The compensatory mutation S128N did not visibly improve recognition of mutant N260Q gp160 by CD4-IgG2. 2014 PloS one Result HIV N260Q;S128N 78;26 83;31 gp160 84 89 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The delay caused by N260Q was not diminished by the addition of S128N. 2014 PloS one Result HIV N260Q;S128N 20;64 25;69 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The mutation at amino acid position 120, changing a valine into an alanine, appeared first during the virus evolution assays as an addition to the pre-existing N260Q gp120 mutation. 2014 PloS one Result HIV N260Q 160 165 gp120 166 171 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The N260Q mutation in gp120 apparently did not revert to WT. 2014 PloS one Result HIV N260Q 4 9 gp120 22 27 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The N260Q mutation increases lysosomal degradation of gp160, gp120 and gp41. 2014 PloS one Result HIV N260Q 4 9 gp120;gp160;gp41 61;54;71 66;59;75 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The presence of chloroquine during virus production resulted for all viruses in an increase in CD4 binding potential, which was most pronounced for the N260Q gp120 mutant. 2014 PloS one Result HIV N260Q 152 157 gp120 158 163 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The R302I mutation on its own did not alter the infectivity of the virus. 2014 PloS one Result HIV R302I 4 9 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The relative increase of incorporated gp160, gp120 and gp41 was more pronounced for mutant N260Q gp120 HIV compared to WT HIV, suggesting that the N260Q mutation in gp160 promoted lysosomal degradation. 2014 PloS one Result HIV N260Q;N260Q 91;147 96;152 gp120;gp120;gp160;gp160;gp41 45;97;38;165;55 50;102;43;170;59 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The S128N compensatory mutation in gp120 has no measurable effect on the gp120/gp41 levels in mutant virus particles. 2014 PloS one Result HIV S128N 4 9 gp120;gp120;gp41 35;73;79 40;78;83 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Therefore, 293T cells were transfected with WT, N260Q or N260Q/S128N gp160-encoding HIV, in the absence or presence of chloroquine. 2014 PloS one Result HIV N260Q;N260Q;S128N 48;57;63 53;62;68 gp160 69 74 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Thus, we identified S128N in the V1/V2-loop as a compensatory mutation to N260Q. 2014 PloS one Result HIV N260Q;S128N 74;20 79;25 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. To confirm that mutant N260Q gp160 is processed in the Golgi, we treated cell lysates of transfected 293T cells with EndoH, which only cleaves high-mannose-type and hybrid-type glycans, but not complex-type glycans. 2014 PloS one Result HIV N260Q 23 28 gp160 29 34 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. To determine to what extent infectivity was restored by the V1/V2-mutations, we introduced the single V120A and S128N mutations and the combined V120A/S128N mutations into the mutant N260Q gp160 background. 2014 PloS one Result HIV N260Q;S128N;S128N;V120A;V120A 183;112;151;102;145 188;117;156;107;150 gp160 189 194 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Using an ELISA, it was confirmed that WT virus is able to bind CD4 substantially better than virus containing the gp120 N260Q or N260Q/S128N mutations. 2014 PloS one Result HIV N260Q;S128N 129;135 134;140 gp120 114 119 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We concluded that lack of the glycosylation site at position 260 severely compromised formation of the CD-binding site and the compensatory mutation in the V1/V2-loop (S128N) did not restore CD4-binding ability. 2014 PloS one Result HIV S128N 168 173 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We demonstrated earlier that mutant N260Q gp160 was CD4-binding compromised. 2014 PloS one Result HIV N260Q 36 41 gp160 42 47 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We have previously shown that in HIV-transfected 293T cells, gp160 containing the N260Q mutation appeared in the Golgi for further processing. 2014 PloS one Result HIV N260Q 82 87 gp160 61 66 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We have previously shown that the N260Q mutation in gp160 of HIV-1 is associated with dramatically lower levels of gp120 and gp41 expression in the virus particle. 2014 PloS one Result HIV N260Q 34 39 gp120;gp160;gp41 115;52;125 120;57;129 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We next performed pulse-chase experiments with WT, N260Q gp160 and N260Q/S128N gp160 to study the effect of these mutations on the kinetics and yields of oxidative folding in the ER. 2014 PloS one Result HIV N260Q;N260Q;S128N 51;67;73 56;72;78 gp160;gp160 57;79 62;84 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We therefore investigated whether the detrimental loss of infectivity due to the N260Q mutation in gp160 could be compensated for by the introduction of a second-site suppressor mutation in gp160. 2014 PloS one Result HIV N260Q 81 86 gp160;gp160 99;190 104;195 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. Because NNRTIs inhibit the excision activity of RT, we next screened each hit for their capacity to inhibit RTs containing the NNRTI resistance mutations K103N, V106A, V179D, Y181C, Y188C or G190A. 2014 The Biochemical journal Result HIV G190A;K103N;V106A;V179D;Y181C;Y188C 191;154;161;168;175;182 196;159;166;173;180;187 NNRTI;NNRTI;RT;RT 8;127;48;108 14;132;50;111 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. Consistent with previously published data, we found that RTs containing M41L/L210W/T215Y or D67N/K70R/T215F/K219Q increased the enzyme's apparent affinity for ATP (KM) and the rate of excision (kexcision) (Table 1). 2014 The Biochemical journal Result HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 92;108;97;77;72;102;83 96;113;101;82;76;107;88 RT 57 60 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. However, while the rates of PPi-mediated excision were found to be ~ 20-fold greater than the rates of ATP-mediated excision, no significant differences in the AZT-MP excision activities were observed between the WT and M41L/L210W/T215Y RTs, as published previously. 2014 The Biochemical journal Result HIV L210W;M41L;T215Y 225;220;231 230;224;236 RT 237 240 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. In contrast, the D67N/K70R enzyme only displayed an increase in the rate of ATP-mediated AZT-MP excision (Table 1). 2014 The Biochemical journal Result HIV D67N;K70R 17;22 21;26 24969820 Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. To identify inhibitors of AZT-MP excision, we screened 3 chemical libraries (7265 compounds in total) using M41L/L210W/T215Y HIV-1 RT and 2 mM ATP. 2014 The Biochemical journal Result HIV L210W;M41L;T215Y 113;108;119 118;112;124 RT 131 133 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. 3.4 Effects of single point mutation L63P on conformational ensemble and comparison to A71V. 2014 FEBS letters Result HIV A71V;L63P 87;37 91;41 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. A recent structure of PR20, a highly resistant construct that contains A71V and L63P, shows similar packing of these residues compared to WT. 2014 FEBS letters Result HIV A71V;L63P 71;80 75;84 PR 22 24 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. A71V is a common secondary mutation seen in multi-drug resistant constructs, and studies suggest this mutation stabilizes the dimer when primary mutations arise. 2014 FEBS letters Result HIV A71V 0 4 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. also showed minimal impact of the A71V mutation on Ki values for Ritonavir, Indinavir and Nelfinavir compared to WT. 2014 FEBS letters Result HIV A71V 34 38 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Although PR20 does not show a predominant closed flap orientation in the absence of inhibitor, this construct also contains the following mutations considered to be within the hydrophobic core: L10F/I13V/I15V/I33F/M36I/-I62V/L90M. 2014 FEBS letters Result HIV I13V;I15V;I33F;I62V;L10F;L90M;M36I 199;204;209;220;194;225;214 203;208;213;224;198;229;218 PR 9 11 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Both L63P and A71V are located away from the active site cavity (Figure 1) in a region of the protein that has been defined by MD simulations as a "cantilever" (residues 59-75), which has anti-correlated motion with the flaps and where mutations in this region are predicted from MD simulations to alter dynamics and flexibility. 2014 FEBS letters Result HIV A71V;L63P 14;5 18;9 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Comparing structures reveals a slight rotation of the side chain of I64 and change in side chain of I62V (Figure S13). 2014 FEBS letters Result HIV I62V 100 104 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Comparison of our L63P S2 values to published results on inhibitor-bound dynamics shows greater flexibility compared to the inhibitor-bound closed conformation. 2014 FEBS letters Result HIV L63P 18 22 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. DEER results show that L63P shifts the conformational ensemble to a more closed-like conformation with a most probable distance of ~33 A. 2014 FEBS letters Result HIV L63P 23 27 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Differences between S2 for subtype B and L63P are given in Figure 4B. 2014 FEBS letters Result HIV L63P 41 45 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Figure 2C shows the results of the population analysis of L63P HIV-1 PR conformational sampling based upon a Gaussian reconstruction of the data in Fig 2B. 2014 FEBS letters Result HIV L63P 58 62 PR 69 71 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Figure 4A compares S2 values for L63P and subtype B. 2014 FEBS letters Result HIV L63P 33 37 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Finally, the shift from reported 35 A in native subtype B to 33 A in L63P and A71V provides evidence that a single amino acid substitution is sufficient to cause a substantial shift in conformations of HIV-1 PR. 2014 FEBS letters Result HIV A71V;L63P 78;69 82;73 PR 208 210 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. From the difference plots in Figure 4B, one can readily see that, on average, L63P is more rigid than subtype B. 2014 FEBS letters Result HIV L63P 78 82 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Given the conformational ensemble for L63P resembles that of PRE, results shows that it is not the absence of the stabilizing mutations, namely Q7K, L33I, and L63I that are present in our subtype B constructs but not in PRE/POST, that cause the alteration to the more closed-like state in PRE. 2014 FEBS letters Result HIV L33I;L63I;L63P;Q7K 149;159;38;144 153;163;42;147 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Interestingly, as discussed more below, both L63P and A71V are located in the same region of the protein (Figure 1) identified as a "cantilever" region located near a hydrophobic cluster, which may have important roles in modulating flexibility and conformational changes of HIV-1 PR through the hydrophobic sliding mechanism. 2014 FEBS letters Result HIV A71V;L63P 54;45 58;49 PR 281 283 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Interestingly, the POST sequence contains hydrophobic core mutations L10I/I15V/M36I, which are mutated positions shared by PR20. 2014 FEBS letters Result HIV I15V;L10I;M36I 74;69;79 78;73;83 PR 123 125 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Kinetic studies of A71V suggest that stabilization of the closed-like state lowers catalytic turnover rate. 2014 FEBS letters Result HIV A71V 19 23 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. L63P is a substitution within the PRE sequence and our results show that this single point mutation may account for the more closed-like conformation of the PRE construct; an ensemble we have seen previously for A71V, with decreased flexibility. 2014 FEBS letters Result HIV A71V;L63P 212;0 216;4 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. L90M may also participate in subtle changes in hydrophobic packing of this region. 2014 FEBS letters Result HIV L90M 0 4 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Recently, we observed similar results for A71V in the absence of inhibitors, and those data are included here for comparison. 2014 FEBS letters Result HIV A71V 42 46 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Recently, we showed by DEER studies that addition of M36I/D30N to A71V restores a predominant semi-open conformation with additional flap curling and open-like states; conformations seen in crystal structures of PR20. 2014 FEBS letters Result HIV A71V;D30N;M36I 66;58;53 70;62;57 PR 212 214 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Results in Figure 2 show that L63P adopts a conformation with a most-probable distance similar to that of PRE. 2014 FEBS letters Result HIV L63P 30 34 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. The conformational ensemble of PRE, giving a predominantly closed-like conformation, was unexpected because, except for A71V, a ligand-free construct with a most probable distance corresponding with the inhibitor induced closed flap conformation has not been reported. 2014 FEBS letters Result HIV A71V 120 124 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. The POST construct contains 8 additional drug-selected polymorphisms, including L10I, I15V, E34Q (negative to uncharged), M36I, T37N, I54A, R57E (positive to negative), and V82A. 2014 FEBS letters Result HIV E34Q;I15V;I54A;L10I;M36I;R57E;T37N;V82A 92;86;134;80;122;140;128;173 96;90;138;84;126;144;132;177 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. The PRE construct differs from subtype B-LAI sequence by four polymorphisms including S37T, P39T, I62V, and L63P, likely the result of natural genetic drift in the mother of the infected child. 2014 FEBS letters Result HIV I62V;L63P;P39T;S37T 98;108;92;86 102;112;96;90 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. This observation is similar to what we recently observed for MDR769 and V6 as well as for accumulating D30N/M36I/A71V mutations, where cross drug resistance is associated with increases in open-like conformations. 2014 FEBS letters Result HIV A71V;D30N;M36I 113;103;108 117;107;112 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. To interrogate backbone dynamics, high-resolution transverse relaxation rate (R2), longitudinal relaxation rate (R1), and (1H)-15N heteronuclear Nuclear Overhauser Enhancement (hNOE) for peptide nitrogen of the L63P were collected and compared to subtype B. 2014 FEBS letters Result HIV L63P 211 215 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. To interrogate what residue(s) may be responsible for the shift in conformation to a close-like state, we generated the single mutant, L36P, which is a common natural polymorphism and a residue that has been studied with molecular dynamics simulations suggesting this site may affect the conformational flexibility. 2014 FEBS letters Result HIV L36P 135 139 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. To our knowledge, no crystal structures for single mutations A71V/L63P or PRE/POST sequence exist to date; but it is likely that substitution at these sites may alter the hydrophobic packing in this region, thus providing the molecular level reason for the altered flexibility and conformational sampling. 2014 FEBS letters Result HIV A71V;L63P 61;66 65;70 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. A subtype-specific polymorphism at position 179 (V179I) was observed among all 16 (100%) subjects infected with HIV-1 subtype A1. 2014 PloS one Result HIV V179I 49 54 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. In the protease gene, three subjects (7%) had major mutations at position 46 (M46I/L) associated with PR drug resistance mutations (Table 3). 2014 PloS one Result HIV M46I;M46L 78;78 84;84 PR;PR 7;102 15;104 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. Some subjects harbored multiple secondary mutations (e.g., subject 905 with V90I and E138K) and/or polymorphisms (e.g., subject 237 with A98S and L101Q).The significance of the observed polymorphisms in HIV-1 non-B subtypes is unknown. 2014 PloS one Result HIV A98S;E138K;L101Q;V90I 137;85;146;76 141;90;151;80 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. The identified NRTI mutations included D67N and K65R, while the NNRTI mutations were V106M and Y181C. 2014 PloS one Result HIV D67N;K65R;V106M;Y181C 39;48;85;95 43;52;90;100 NNRTI;NRTI 64;15 69;19 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. The most frequent polymorphisms were seen at positions M36I (81%), H69K (86%), L89M (74%), and I93L (62%). 2014 PloS one Result HIV H69K;I93L;L89M;M36I 67;95;79;55 71;99;83;59 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. The commonest NRTI mutation observed was M184V (8/19) and the most common NNRTI was K103N/S (6/19). 2014 ISRN AIDS Result HIV K103N;K103S;M184V 84;84;41 91;91;46 NNRTI;NRTI 74;14 79;18 25008864 SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma. A subset of these are non-synonymous or putative functional SNPs located in genes with relevance to cancer, including rs1116221 G>A, a missense (Glu421Lys) polymorphism in TRIM31 (OR=0.74; 95% CI: 0.56-0.96; p=0.033), rs909253 A>G in the 5'UTR of LT-alpha (OR=0.75; 95% CI: 0.58-0.96; p=0.022) and occurring in strong LD with non-synonymous SNP rs1041981 C>A (Thr60Asn) in the same gene (OR=0.75; 95% CI: 0.58-0.96; p=0.022), and rs3093665 A>C in the 3'UTR of TNF-alpha with a stronger effect but marginally associated (OR=2.1; 95% CI: 0.93-4.71; p=0.075) with the risk, possibly due to a low minor allele frequency (MAF). 2014 Genes and immunity Result HIV E421K;T60N 145;360 154;368 25008864 SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma. Within 95 Kb from HLA-DMB toward HLA-DR, significant but moderate associations with risk were observed with two non-synonymous SNPs in TAP1, rs1800453 A>G (Asp697Gly) (OR=1.54; 95%: 1.09-2.18; p=0.014) and rs4148880 A>G (Ile393Val) (OR=1.45; 95% CI: 1.05-1.99; p=0.024), and with rs2071541 A>G, a SNP located in the overlapping microRNA TAPSAR1 (OR=1.60; 95% CI: 1.11-2.32; p=0.012). 2014 Genes and immunity Result HIV D697G;I393V 156;221 165;230 Asp 156 159 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. 1A), was as fit as its cognate T/F virus, but the fitness of the T242N mutant, which differed from the T/F virus by only the T242N CD8+ T cell escape mutation, was severely impaired. 2014 PloS one Result HIV T242N;T242N 65;125 70;130 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. 3E and 3G), similar to what we previously observed for the comparison between the T242N mutant and the T/F virus. 2014 PloS one Result HIV T242N 82 87 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. 4C and 4D), indicating that the partial CD8+ T cell escape mutation G248A did not significantly affect the fitness of its cognate T/F virus. 2014 PloS one Result HIV G248A 68 73 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Both fitness loss and slight fitness gain were observed for the G248A mutation when it was analyzed in a heterologous viral genome NL4-3 in vitro . 2014 PloS one Result HIV G248A 64 69 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Both T242N and G248A mutations were previously identified CD8+ T cell escape mutations. 2014 PloS one Result HIV G248A;T242N 15;5 20;10 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. During three additional passages, both NI and NA mutants continuously outgrew the T242N mutant. 2014 PloS one Result HIV T242N 82 87 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Homology modeling of p24 monomers did not result in substantial structural differences in helix 6 between Thr in the T/F virus and Asn in the T242N mutant (0.45A backbone atom RMSD), suggesting that the T242N escape mutation in the context of the full-length p24 is not expected to destabilize the helix 6 structure. 2014 PloS one Result HIV T242N;T242N 142;203 147;208 p24;p24 21;259 24;262 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. In addition, only modest changes in the neighboring CypA-binding loop and N-terminal hairpin were observed in the T242N model (1.05 A and 2.52 A backbone atom RMSD, respectively). 2014 PloS one Result HIV T242N 114 119 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. In the single-passage assay, NI was 6+-1% more fit than the T242N mutant (p = 0.02), while NA was 7+-1% more fit than the T242N mutant (p = 0.01). 2014 PloS one Result HIV T242N;T242N 60;122 65;127 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Interestingly, the structural differences from the T/F model in the N-terminal hairpin region were smaller in the NIA model than in the T242N model. 2014 PloS one Result HIV T242N 136 141 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. No measurable impact on the fitness of the cognate T/F virus was detected for the V247I or G248A mutation. 2014 PloS one Result HIV G248A;V247I 91;82 96;87 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Our previous study showed that the NIA mutant, which contained three mutations (T242N, V247I and G248A) in the TW10 epitope in patient CH77. 2014 PloS one Result HIV G248A;T242N;V247I 97;80;87 102;85;92 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Peptides containing the T242N mutation led to a complete escape from the T cell response. 2014 PloS one Result HIV T242N 24 29 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Previous studies showed that the G248A mutation remained stable upon transmission to HLA-B57/5801 negative recipients, suggesting little or no fitness cost of this mutation in vivo . 2014 PloS one Result HIV G248A 33 38 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. R355K was the earliest CD8+ T cell escape mutation in CH77 selected by T cell responses targeting the epitope Env352-360 . 2014 PloS one Result HIV R355K 0 5 Env 110 113 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The CD8+ T cell escape mutation G248A is commonly associated with T242N in subtype B virus; 44% (123 of 278) of the subtype B viral sequences with N242 also had A248 in the HIV Sequence Database (http://www.hiv.lanl.gov). 2014 PloS one Result HIV G248A;T242N 32;66 37;71 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The early partial CD8+ T cell escape mutation R355K in Env did not cause fitness loss. 2014 PloS one Result HIV R355K 46 51 Env 55 58 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The I64T mutant was as fit as its cognate T/F virus in the single-passage assay (sij = 0.01+-0.01; p = 0.63). 2014 PloS one Result HIV I64T 4 8 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The I64T reversion mutation in the Tat/Rev overlapping region was one of the two earliest mutations detected in CH77. 2014 PloS one Result HIV I64T 4 8 Rev;Tat 39;35 42;38 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The modeling of all three mutations (T242N, V247I and G248A) also showed no significant perturbation of helix 6 (0.74 A backbone atom RMSD), and only minor differences in the CypA loop and N-terminal hairpin compared to the T/F sequence model (0.89 A and 1.06 A backbone RMSD, respectively). 2014 PloS one Result HIV G248A;T242N;V247I 54;37;44 59;42;49 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The peptides containing the V247I mutation, the G248A mutation, or both mutations (V247I/G248A) were partially recognized compared to the wt TW10 peptide. 2014 PloS one Result HIV G248A;G248A;V247I;V247I 48;89;28;83 53;94;33;88 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The result showed that the G248A mutant was as fit as the T/F virus in both single-passage (sij = -0.02+-0.01; p = 0.07) and multiple-passage assay (sij = 0.03+-0.01; p = 0.16). 2014 PloS one Result HIV G248A 27 32 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The reversion mutation I64T in Tat/Rev overlapping region had no measurable fitness cost. 2014 PloS one Result HIV I64T 23 27 Rev;Tat 35;31 38;34 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The reversion/escape mutation V247I or the CD8+ T cell escape mutation G248A partially restored the fitness loss caused by the T242N mutation. 2014 PloS one Result HIV G248A;T242N;V247I 71;127;30 76;132;35 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The T242N, NI and NA mutants, which all contained the T242N CD8+ T cell escape mutation, replicated at slightly lower levels than other viruses between day 3 and day 5 (~1.6-fold lower than the T/F virus). 2014 PloS one Result HIV T242N;T242N 4;54 9;59 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The V247I mutation was a reversion mutation towards the subtype B consensus sequence and was recognized equally well by the autologous T cells at day 592. 2014 PloS one Result HIV V247I 4 9 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The V247I or G248A mutation caused partial escape from the early T cell responses. 2014 PloS one Result HIV G248A;V247I 13;4 18;9 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. These results demonstrated that the V247I or G248A mutation alone could partially restore the fitness loss caused by the T242N mutation in the TW10 epitope, but only both together could fully compensate the fitness cost due to the T242N mutation as previously demonstrated. 2014 PloS one Result HIV G248A;T242N;T242N;V247I 45;121;231;36 50;126;236;41 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. These results were in agreement with previous studies, which reported that the G248A mutation alone caused partial loss of the T cell recognition, while the T242N mutation led to a complete escape from the T cell responses targeting the TW10 epitope. 2014 PloS one Result HIV G248A;T242N 79;157 84;162 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. This result showed that, in addition to the reversion mutation V247I, the reversion mutation I64T also did not cause measurable fitness costs in its cognate T/F virus in an in vitro fitness assay. 2014 PloS one Result HIV I64T;V247I 93;63 97;68 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Three mutations (T242N, V247I and G248A) were detected in all viral genomes in the TW10 epitope at day 592 post Fiebig stage I/II in subject CH77. 2014 PloS one Result HIV G248A;T242N;V247I 34;17;24 39;22;29 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Thus, both V247I and G248A were early weak CD8+ T cell escape mutations, while the T242N was a potent CD8+ T cell escape mutation in CH77. 2014 PloS one Result HIV G248A;T242N;V247I 21;83;11 26;88;16 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Thus, the rapid reversion of Ile to Thr at position 64 in Tat could not be caused by the selection pressure from T cell responses. 2014 PloS one Result HIV I64T 29 54 Tat 58 61 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Thus, the V247I mutation, as a reversion mutation and partial CD8+ T cell escape mutation, had no measurable impact on the fitness of its cognate T/F virus. 2014 PloS one Result HIV V247I 10 15 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. To determine whether the V247I or G248A mutation alone could fully compensate the fitness loss due to the T242N mutation, we compared the NI or NA mutant to the T242N mutant. 2014 PloS one Result HIV G248A;T242N;T242N;V247I 34;106;161;25 39;111;166;30 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. To further investigate whether this early CD8+ T cell escape mutation alone had any fitness cost, we compared the R355K mutant with the T/F virus. 2014 PloS one Result HIV R355K 114 119 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. To more clearly define its impact on viral fitness, we determined the relative fitness between the G248A mutant and its cognate T/F virus. 2014 PloS one Result HIV G248A 99 104 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. To test whether this reversion mutation had any impact on the viral fitness, we compared the viral fitness between the I64T mutant and the T/F virus. 2014 PloS one Result HIV I64T 119 123 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. To understand whether the fitness cost and compensation of the T242N, V247I and G248A mutations could be explained by alterations in the structure, stability or assembly of the p24 protein, we modeled their potential impact on the p24 structure based on the recently published structural data. 2014 PloS one Result HIV G248A;T242N;V247I 80;63;70 85;68;75 p24;p24 177;231 180;234 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. To understand whether these mutations, independently or together with other mutations, could affect the fitness of their cognate T/F virus or mutants selected by CD8+ T cell in vivo, we generated four single-mutation IMCs, each of which contained a single reversion mutation (V247I or I64T) or a single CD8+ T cell escape mutation (V247I, G248A or R355K) and two double-mutation IMCs, each of which contained two mutations (NI containing T242N and V247I, and NA containing T242N and G248A). 2014 PloS one Result HIV G248A;G248A;I64T;R355K;T242N;T242N;V247I;V247I;V247I 339;483;285;348;438;473;276;332;448 344;488;289;353;443;478;282;337;453 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. We also showed that an early mutant (TK), which contained a reversion mutation (I64T) in Tat/Rev and a CD8+ T cell escape mutation (R355K) in Env, was similarly fit to the CH77 T/F virus. 2014 PloS one Result HIV I64T;R355K 80;132 84;137 Rev;Tat;Env 93;89;142 96;92;145 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. We next investigated if the V247I or G248A mutation alone could fully restore the fitness of the T242N mutant to the T/F level. 2014 PloS one Result HIV G248A;T242N;V247I 37;97;28 42;102;33 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. We next sought to determine whether the V247I or G248A mutation compensated for the fitness loss due to the T242N mutation because they could render their cognate T/F virus more fit. 2014 PloS one Result HIV G248A;T242N;V247I 49;108;40 54;113;45 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. We previously showed that the mutant TK, which contained both R355K and I64T mutations, did not cause any fitness loss when compared to the T/F virus. 2014 PloS one Result HIV I64T;R355K 72;62 76;67 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. When the V247I mutant was compared with the T/F virus, no significant fitness differences were observed between the two viruses in both single-passage assay (sij = -0.02+-0.02; p = 0.44) and multiple-passage assay (sij = -0.02+-0.06, p = 0.77). 2014 PloS one Result HIV V247I 9 14 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. All of these plus an additional 6 infants were positive by the Y181C AS-PCR (mean quantitative percentage value measure (mu)=43.28%). 2014 Journal of virological methods Result HIV Y181C 63 68 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Although fewer samples were positive for K103N, the trend line showed a clear correlation between data from both assays. 2014 Journal of virological methods Result HIV K103N 41 46 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Correlation of quantitative levels of Y181C and K103N detection between AS-PCR and UDPS. 2014 Journal of virological methods Result HIV K103N;Y181C 48;38 53;43 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Five samples showed discordance for Y181C and 11 for K103N between the 2 assays. 2014 Journal of virological methods Result HIV K103N;Y181C 53;36 58;41 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Five specimens were discordant for Y181C and 11 for K103N. 2014 Journal of virological methods Result HIV K103N;Y181C 52;35 57;40 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. For this study we made use of these available datasets to directly compare AS-PCR and UDPS for detection of Y181C and K103N, the major mutations selected following sdNVP. 2014 Journal of virological methods Result HIV K103N;Y181C 118;108 123;113 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Frequency of Y181C and K103N mutant detection using different technologies. 2014 Journal of virological methods Result HIV K103N;Y181C 23;13 28;18 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. In these cases, the sample used for UDPS were 25 and 41 days later than those used for AS-PCR which may have contributed to the lower sensitivity of UDPS, particularly given that Y181C fades relatively quickly. 2014 Journal of virological methods Result HIV Y181C 179 184 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K103N was detected in 5 samples by UDPS and not by AS-PCR. 2014 Journal of virological methods Result HIV K103N 0 5 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Of note, two specimens with highly discrepant results for K103N each had unusual polymorphisms at position 102 (K102T in specimen #3 and K102R at specimen #5). 2014 Journal of virological methods Result HIV K102R;K102T;K103N 137;112;58 142;118;63 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Of the 11 specimens discordant for K103N, three had major discrepancies. 2014 Journal of virological methods Result HIV K103N 35 40 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. One additional specimen showed minor discordance for Y181C in that the mutation was detected by UDPS at 2.62% but negative by AS-PCR, suggesting in this case the AS-PCR was less sensitive. 2014 Journal of virological methods Result HIV Y181C 53 58 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. One of these (sample 3) was positive for K103N by population-sequence genotyping and AS-PCR, but the mutation was not detected by UDPS. 2014 Journal of virological methods Result HIV K103N 41 46 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Sample 11 had an unusual polymorphism (K103T) which alternatively may have contributed to a false positive in the AS-PCR assay. 2014 Journal of virological methods Result HIV K103T 39 44 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The assay results were significantly correlated for detection of both mutations (p<0.0001), with correlation coefficients of 0.94 (95% CI 0.91-0.96) and 0.89 (95% CI 0.84 - 0.92) for Y181C and K103N respectively. 2014 Journal of virological methods Result HIV K103N;Y181C 193;183 198;188 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The K103N mutation was detected in 4 infants (4%) by population sequencing, in 9 infants (9%) by AS-PCR (4 at high levels [20.56% - 99.93%; mu=69.70%] and 5 at low levels [0.60% - 15.06%; mu=1.14%]), and in 8 specimens by UDPS (8%; 3 at high levels (31.38% - 99.60%; mu=82.60%) and 5 at low levels (1.00% - 14.62%; mu=1.80%)). 2014 Journal of virological methods Result HIV K103N 4 9 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The K103N showed a larger number of discordances compared to Y181C. 2014 Journal of virological methods Result HIV K103N;Y181C 4;61 9;66 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The kappa statistic for detection of K103N was 0.2962 (standard error 0.0974) with only fair agreement between the two assays. 2014 Journal of virological methods Result HIV K103N 37 42 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The kappa statistic for detection of the Y181C mutation using AS-PCR and UDPS was determined to be 0.8739 (standard error 0.0973), with very good strength of agreement between the AS-PCR and UDPS assays. 2014 Journal of virological methods Result HIV Y181C 41 46 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The other four samples were 2% or less by UDPS and may reflect higher sensitivity of UDPS for K103N compared to AS-PCR in these cases. 2014 Journal of virological methods Result HIV K103N 94 99 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The quantitative percentage values of Y181C and K103N mutants as determined by AS-PCR and ultra-deep sequencing were compared for all 105 samples (Figure 1). 2014 Journal of virological methods Result HIV K103N;Y181C 48;38 53;43 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The samples that were discordant for Y181C or K103N between the 2 technologies were further investigated (Table 2). 2014 Journal of virological methods Result HIV K103N;Y181C 46;37 51;42 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The total number of samples where the Y181C and K103N mutations were detected by population sequencing, AS-PCR and UDPS are shown in Table 1A. 2014 Journal of virological methods Result HIV K103N;Y181C 48;38 53;43 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. These data also confirm the higher prevalence of Y181C relative to K103N in infants who receive sdNVP for pMTCT. 2014 Journal of virological methods Result HIV K103N;Y181C 67;49 72;54 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Thirty-six specimens were excluded from analysis for the following reasons: 12 specimens had viral loads that were too low for UDPS (<100,000 copies/mL) at the time of study, UDPS failed in 7 specimens, the Y181C AS-PCR was not successful in 2 specimens, 1 specimen had a false positive Y181C AS-PCR due to a Y181FS polymorphism, and phylogenetic relatedness between plasma sequences from both laboratories and UDPS consensus sequences was not confirmed in 14 specimens. 2014 Journal of virological methods Result HIV Y181C;Y181C;Y181F;Y181S 207;287;309;309 212;292;315;315 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Twenty-four specimens were positive and 76 negative for Y181C in both assays, and 3 positive and 91 negative for K103N. 2014 Journal of virological methods Result HIV K103N;Y181C 113;56 118;61 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Two specimens with minor discordant K103N results had Y181C detected equally by AS-PCR and UDPS (data not shown). 2014 Journal of virological methods Result HIV K103N;Y181C 36;54 41;59 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Y181C was detected by population sequencing in 22 of 105 (21%) specimens. 2014 Journal of virological methods Result HIV Y181C 0 5 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Y181C was not detected by UDPS in four specimens that were positive by AS-PCR, of which two were also positive by population genotyping of the same amplicon. 2014 Journal of virological methods Result HIV Y181C 0 5 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. A98G confers a low level of resistance to EFV and NVP, and while V179D in a URF strain confers a low level of resistance against EFV and an intermediate level of resistance against NVP, V179D in CRF01_AE does not affect resistance to any RT drugs. 2014 AIDS research and therapy Result HIV V179D;V179D;A98G 65;186;0 70;191;4 RT 238 240 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. G190A confers a high level of resistance to NVP and an intermediate level of resistance to EFV. 2014 AIDS research and therapy Result HIV G190A 0 5 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. However, some accessory mutations that did not affect susceptibility to ARV drugs were found in the protease gene, including L10I/L/V (3.0%; 4/133), V11I/V (3.0%; 4/133), L33F (2.3%; 3/133), and A71A/V/T (12.8%; 17/133). 2014 AIDS research and therapy Result HIV A71A;A71T;A71V;L10I;L10L;L10V;L33F;V11I;V11V 195;195;195;125;125;125;171;149;149 203;203;203;133;133;133;175;155;155 PR 100 108 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. However, two other mutations which confer resistance to RTIs, A98G and V79D, were not included in the 2009 WHO SDRM list but were identified here. 2014 AIDS research and therapy Result HIV A98G;V79D 62;71 66;75 RT 56 60 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. L210W confers a low level of resistance to zidovudine (AZT) and stavudine (D4T). 2014 AIDS research and therapy Result HIV L210W 0 5 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. T69A/N/S, V179E and P236L were polymorphism mutations against RTIs. 2014 AIDS research and therapy Result HIV P236L;T69A;T69N;T69S;V179E 20;0;0;0;10 25;8;8;8;15 RT 62 66 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. The sole NRTI-related SDRM was L210W, detected in two individuals infected with CRF01_AE strains (from Anqing and Ma'anshan). 2014 AIDS research and therapy Result HIV L210W 31 36 NRTI;Matrix 9;114 13;116 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. The two NNRTI-related SDRMs were Y181C and G190A, found in persons infected with CRF01_AE (from Xuancheng) and B (from Anqing) strains, respectively (Table 3). 2014 AIDS research and therapy Result HIV G190A;Y181C 43;33 48;38 NNRTI 8 13 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. Y181C confers a high level of resistance to nevirapine (NVP) and an intermediate level of resistance to efavirenz (EFV), etravirine (ETR) and rilpivirine (RPV). 2014 AIDS research and therapy Result HIV Y181C 0 5 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. Figure 1B shows that both the prevalence of the TAMs and corresponding revertants and the M184V mutations were stable over time (OR, 1.07 [95% CI, 0.98-1.18]; p = 0.13 and 0.79 [95% CI, 0.56-1.10]; p = 0.16, respectively). 2014 BMC infectious diseases Result HIV M184V 90 95 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. However, this explanation is not plausible as phylogenetic analyses showed several different clusters containing the K103N amino acid substitution and these clusters were comprised of only a small number of patients (Figure 2). 2014 BMC infectious diseases Result HIV K103N 117 122 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. The highest prevalence was found for the revertant mutations at position 215 (S/D/C/E/I/V at 2.7%), followed by M41L (1.7%), and L210W (0.6%). 2014 BMC infectious diseases Result HIV L210W;M41L 129;112 134;116 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. The M184V mutation can be selected by the drugs emtricitabine, lamivudine, and abacavir. 2014 BMC infectious diseases Result HIV M184V 4 9 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. The most prevalent drug resistant mutations were K103N (1.7%), G190A (0.5%), Y181C (0.4%) for NNRTI and L90M (0.6%) for PI. 2014 BMC infectious diseases Result HIV G190A;K103N;L90M;Y181C 63;49;104;77 68;54;108;82 NNRTI;PI 94;120 99;122 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. We detected the M184V mutation in 16 patients (0.4%). 2014 BMC infectious diseases Result HIV M184V 16 21 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. A number of polymorphisms were present in protease at both screening and failure: E35D, L63P, I72V, V77I and I93L (Table S1). 2014 The Journal of antimicrobial chemotherapy Result HIV E35D;I72V;I93L;L63P;V77I 82;94;109;88;100 86;98;113;92;104 PR 42 50 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. A number of protease polymorphisms were present both at baseline and time of treatment failure: I13V, K14R, K20I, E35Q, M36I, R41K, R57K, Q61N, C67E, H69K, V82I and L89M (Table S1). 2014 The Journal of antimicrobial chemotherapy Result HIV C67E;E35Q;H69K;I13V;K14R;K20I;L89M;M36I;Q61N;R41K;R57K;V82I 144;114;150;96;102;108;165;120;138;126;132;156 148;118;154;100;106;112;169;124;142;130;136;160 PR 12 20 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. A number of protease polymorphisms were present both at baseline and time of treatment failure: N37S, P39Q, I62V, L63P, V77I and I93L. 2014 The Journal of antimicrobial chemotherapy Result HIV I62V;I93L;L63P;N37S;P39Q;V77I 108;129;114;96;102;120 112;133;118;100;106;124 PR 12 20 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. Clonal sequence analysis revealed the presence of the V82A major PI resistance mutation in 1 of the 10 viral variants isolated from the time of treatment failure, as well as a number of protease polymorphisms at both screening and failure (Table S1, available as Supplementary data at JAC Online). 2014 The Journal of antimicrobial chemotherapy Result HIV V82A 54 58 PR;PI 186;65 194;67 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. In addition, a number of mutations previously associated with PI susceptibility or resistance in Gag were present at both screening and time of treatment failure: E12K, R76K, T375N, I376V and L449P (Table S2). 2014 The Journal of antimicrobial chemotherapy Result HIV E12K;I376V;L449P;R76K;T375N 163;182;192;169;175 167;187;197;173;180 Gag;PI 97;62 100;64 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. In addition, a number of mutations that have been previously associated with PI susceptibility or resistance in Gag were present at both screening and time of treatment failure: E12K, R76K, H219Q, V370A, R380K, K436R and S451N (Table S2). 2014 The Journal of antimicrobial chemotherapy Result HIV E12K;H219Q;K436R;R380K;R76K;S451N;V370A 178;190;211;204;184;221;197 182;195;216;209;188;226;202 Gag;PI 112;77 115;79 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. In addition, a number of mutations that have been previously associated with PI susceptibility or resistance in Gag were present at both screening and time of treatment failure: E12K, R76K, V370A and L449P (Table S2). 2014 The Journal of antimicrobial chemotherapy Result HIV E12K;L449P;R76K;V370A 178;200;184;190 182;205;188;195 Gag;PI 112;77 115;79 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. In addition, a number of mutations that have been previously associated with PI susceptibility or resistance in Gag were present at both screening and time of treatment failure: Y79F, T81A, M200I, H219Q, S373P, T375N, R380K, I389T and S451N (Table S2). 2014 The Journal of antimicrobial chemotherapy Result HIV H219Q;I389T;M200I;R380K;S373P;S451N;T375N;T81A;Y79F 197;225;190;218;204;235;211;184;178 202;230;195;223;209;240;216;188;182 Gag;PI 112;77 115;79 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. In contrast, F6 and F9 displayed susceptibilities similar to the assay reference strain to atazanavir and lopinavir, despite emergence of Y79F (Figure 2a). 2014 The Journal of antimicrobial chemotherapy Result HIV Y79F 138 142 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. Of note, the F5 variant containing the major PI resistance mutation V82A displayed significantly reduced susceptibility to lopinavir (17-fold). 2014 The Journal of antimicrobial chemotherapy Result HIV V82A 68 72 PI 45 47 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. Only one change in Gag associated with PI susceptibility or resistance was present:V370A (V/A mixture pre-therapy and all V370A at failure, Tables S1 and S2). 2014 The Journal of antimicrobial chemotherapy Result HIV V370A;V370A 83;122 88;127 Gag;PI 19;39 22;41 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. Overall, E12K, T81A and M36I were of greatest interest as they have been previously associated with PI exposure and reduced susceptibility. 2014 The Journal of antimicrobial chemotherapy Result HIV E12K;M36I;T81A 9;24;15 13;28;19 PI 100 102 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. T81A was seen in only 1 of 10 screening variants but in all failure variants. 2014 The Journal of antimicrobial chemotherapy Result HIV T81A 0 4 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. The emergence of Y79F in failure variant 6 (F6) and F9 correlated with PI exposure. 2014 The Journal of antimicrobial chemotherapy Result HIV Y79F 17 21 PI 71 73 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. The minor resistance mutation A71T was present in protease of viral variants from screening and the time of treatment failure, along with a number of polymorphisms: I13A, K20I, M36I, R41K, H69K, L89I and I93M (Table S1). 2014 The Journal of antimicrobial chemotherapy Result HIV A71T;H69K;I13A;I93M;K20I;L89I;M36I;R41K 30;189;165;204;171;195;177;183 34;193;169;208;175;199;181;187 PR 50 58 25108107 A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF. Among the four MDR769 HIV-1 protease variants (I10V, A82F, A82S and A82T) that were co-crystallized with TLF-PafF, diffraction quality crystals were obtained for the I10V and A82S variants. 2014 Journal of molecular graphics & modelling Result HIV A82F;A82S;A82S;A82T;I10V;I10V 53;59;175;68;47;166 57;63;179;72;51;170 PR 28 36 25108107 A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF. While the I10V variant yielded a good quality X-ray diffraction data, the A82S diffracted poorly and the data was unusable. 2014 Journal of molecular graphics & modelling Result HIV A82S;I10V 74;10 78;14 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. Among the 10 with virologic outcome, 7 experienced virologic failure: 3 of these participants had single mutations (K103N, n=2; Y181C, n=1); 2 participants had 2 mutations (K103N and G190A, n=1; Y181C and G190A, n=1); and 2 participants had 3 mutations (K103N, M184V, and Y181C). 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;G190A;K103N;K103N;K103N;M184V;Y181C;Y181C;Y181C 183;205;116;173;254;261;128;195;272 188;210;121;179;259;266;133;200;277 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. Consensus sequencing confirmed baseline mutations in 6 of the 7 participants identified by OLA, and detected baseline mutations at sites associated with "potential low-level resistance" to didanosine and abacavir or "low-level resistance" to zidovudine and stavudine in 4 additional participants at codons not evaluated by OLA (T215T/I, n=1; T69S, n=1; T69T/N, n=2) (hivdb.stanford.edu). 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV T215I;T215T;T69N;T69S;T69T 328;328;353;342;353 335;335;359;346;359 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. In addition to the 7 participants who had mutations identified by OLA, pyrosequencing detected 17 additional participants with either very low (<2%) frequency mutations at the codons tested by OLA (M184V, K103N, Y181C, G190A), or mutations (frequencies 0.1%-100%) in other codons conferring drug-resistance. 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K103N;M184V;Y181C 219;205;198;212 224;210;203;217 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. In another, Y181C was detected at baseline with additional mutations, and at failure it had shifted to Y181V (Figure 3). 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C;Y181V 12;103 17;108 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. In one participant, K103N at a frequency of 5% co-existed with G190A; only the latter was detected at failure along with Y181C and M184V. 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K103N;M184V;Y181C 63;20;131;121 68;25;136;126 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. Of these 5 participants, 3 participants had a single mutation (K103N), 1 participant had 2 mutations (K013N and M184V), and 1 participant had 3 mutations (K103N, Y181C, and G190A). 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K013N;K103N;K103N;M184V;Y181C 173;102;63;155;112;162 178;108;68;160;117;167 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. The remaining 6 individuals had mutations at non-OLA codons, all at frequencies <2%, except for 3 individuals: one with L210W detected at a frequency of 5.9%, and two with T69N detected; one at a frequency of 22.5% and the second at 25.0% (Figure 3). 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV L210W;T69N 120;172 125;176 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. This was also true when restricted to codons evaluated by OLA (K103N, Y181C, G190A, and M184V). 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K103N;M184V;Y181C 77;63;88;70 82;68;93;75 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. Three participants with mutations detected by OLA at baseline did not experience virologic failure after 18 months on ART and each had only a single mutation (K103N); their mutant viral loads were 112,316, 642,240, and 585,469 copies/mL. 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 159 164 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. When examining OLA codons (K103N, Y181C, G190A, and M184V), the mean time to virologic failure was significantly earlier among participants with baseline mutation frequencies >=2% by pyrosequencing compared to those with minority mutations (>0% to <2%) (p=0.002) or no mutations (0%) (p=0.008) (Figure 4). 2014 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K103N;M184V;Y181C 41;27;52;34 46;32;57;39 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. A total of 35 patients had at least 1 TAM, with the following distribution: M41L (16%), D67N (15%), K70R (9%), L210W (11%), T215Y (16%), T215F (11%), K219Q (5%) and K219E (2%). 2014 Journal of the International AIDS Society Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 88;165;150;100;111;76;137;124 92;170;155;104;116;80;142;129 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. As the results of this sensitivity analysis are similar to those presented in Table 2, the absence of K65R in our multi-NRTI RAM definition did not significantly alter the analysis outcome. 2014 Journal of the International AIDS Society Result HIV K65R 102 106 NRTI 120 124 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Figures 1 and 2 show that the most common NRTI RAM was M184V (79/105, 75%), followed by M41L and T215Y (both 17 patients each, 16%), and the most common NNRTI RAM was Y181C (37 patients, 35%), followed by K103N (34 patients, 32%). 2014 Journal of the International AIDS Society Result HIV K103N;M184V;M41L;T215Y;Y181C 205;55;88;97;167 210;60;92;102;172 NNRTI;NRTI 153;42 158;46 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Major PI RAMs found in the two patients were M46L, G48V, V82A, N83D and L90M. 2014 Journal of the International AIDS Society Result HIV G48V;L90M;M46L;N83D;V82A 51;72;45;63;57 55;76;49;67;61 PI 6 8 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Of the 39 patients harbouring multi-NRTI RAMs, there were six patients with Q151M, 24 with >=2 TAMs and 32 with M184V+>=1 TAM. 2014 Journal of the International AIDS Society Result HIV M184V;Q151M 112;76 117;81 NRTI 36 40 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. When K65R was included in the sensitivity analysis, a total of 46/105 (44%) patients were classified as harbouring multi-NRTI RAMs. 2014 Journal of the International AIDS Society Result HIV K65R 5 9 NRTI 121 125 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Among the variants of FNC, P-5, P-11 and P-16 had no M184V mutation and there was a 2.08% frequency of M184V in P-21. 2014 PloS one Result HIV M184V;M184V 53;103 58;108 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. FNC and 3TC were both sensitive to NRTIs-resistant strain HIV-174V, PIs-resistant strains HIV-1L10R/M46I/L63P/V82T/I84V and HIV-1RF V82F/184V, and FIs-resistant strain pNL4-3 gp41 (36G) V38A/N42T (Table 1). 2014 PloS one Result HIV M46I 100 104 gp41;NRTI;PI 175;35;68 179;40;71 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. FNC showed cross-resistance to it with EC50 of 27.45 nM while 3TC could not inhibit the replication of HIV-1LAV-M184V with concentration higher than 800 microM. 2014 PloS one Result HIV M184V 112 117 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. HIV-1LAV-M184V was used as a control in this assay since it is a highly resistant strain to 3TC. 2014 PloS one Result HIV M184V 9 14 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. However, resistance correlation of L214F was not observed in the variants of 3TC. 2014 PloS one Result HIV L214F 35 40 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. In 3TC- induced variants, a high M184V frequency of 45.83% emerged at P-11 and over 50% at P-16 and P-21. 2014 PloS one Result HIV M184V 33 38 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. L214F showed high induced resistance correlation with FNC and the frequency of L214F ranged from 30.30% to 100% in P-5 to P-21 variants whereas similar. 2014 PloS one Result HIV L214F;L214F 79;0 84;5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. M184V/I was the highest resistant substitution for both FNC and 3TC which agreed with the result of phenotypic resistance assay. 2014 PloS one Result HIV M184I;M184V 0;0 7;7 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Since L214F showed higher induced resistance correlation with FNC but not 3TC, we examined the binding modes of FNC and 3TC with L214. 2014 PloS one Result HIV L214F 6 11 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The emergence of mutation L214F will result in stronger hydrophobic interaction between residues F214 and F160, which will pull the F160 away from FNC. 2014 PloS one Result HIV L214F 26 31 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The extent of steric hindrance differs between FNC and 3TC with the former causing greater interference in mutant M184I than M184V due to presence of the azido group (Figure 3C and D). 2014 PloS one Result HIV M184I;M184V 114;125 119;130 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The frequencies of M184I/V in FNC and 3TC induced variants presented obvious rising trend, but the frequencies of M184I and M184V were significantly different. 2014 PloS one Result HIV M184I;M184I;M184V;M184V 19;114;19;124 26;119;26;129 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The variants of FNC were gave preference to M184I, while those of 3TC preferred M184V. 2014 PloS one Result HIV M184I;M184V 44;80 49;85 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. This suggests mutant M184I is more resistant to FNC than mutant M184V. 2014 PloS one Result HIV M184I;M184V 21;64 26;69 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Thus, the mutation L214F disrupts the interaction between FNC and residue F160, it affects the binding of FNC but not 3TC to RT (Figure 4). 2014 PloS one Result HIV L214F 19 24 RT 125 127 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. However, K103N tend to be more frequent in naive patients than in pre-treated patients (n = 5, 71.4% versus n = 5, 33.3%), (p = 0.09). 2014 PloS one Result HIV K103N 9 14 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. In five pre-treated patients, viruses were found resistant to etravirine (ETR), a second-generation NNRTI drug, due to the simultaneous presence of the Y181C and G190A mutations. 2014 PloS one Result HIV G190A;Y181C 162;152 167;157 NNRTI 100 105 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. L74V/I/IL was seen in 20% of pre-treated patients, not in naive patients. 2014 PloS one Result HIV L74I;L74L;L74V 0;0;0 9;9;9 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. Multi-Nucleos(t)ide Resistance (MNR) were only observed in pre-treated patients, including 2 (13.3%) harboring Q151M, K65R, E33A/D, E44A/D mutations. 2014 PloS one Result HIV E33A;E33D;E44A;E44D;K65R;Q151M 124;124;132;132;118;111 130;130;138;138;122;116 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. Regarding the NNRTI mutations, V90L, K101E, K103N/S, V106I/M, V1791L were observed in both patients groups. 2014 PloS one Result HIV K101E;K103N;K103S;V106I;V106M;V1791L;V90L 37;44;44;53;53;62;31 42;51;51;60;60;68;35 NNRTI 14 19 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. The most common NRTI mutations were the M184V mutation (19/22, 86.3%). 2014 PloS one Result HIV M184V 40 45 NRTI 16 20 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. The TAM1 pathway was present mostly in pre-treated patients (M41L 4/15, 27.7%; L210W: 3/15, 20%, T215Y/I/Y: 6/15, 40%). 2014 PloS one Result HIV L210W;M41L;T215I;T215Y 79;61;97;97 84;66;106;106 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. The TAM2 pathway (D67N, K70R, T215F, and K219Q/E) was present in 5/22, 4/22, 8/22, 2/22 patients. 2014 PloS one Result HIV D67N;K219E;K219Q;K70R;T215F 18;41;41;24;30 22;48;48;28;35 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. The Y181C/I (N = 5, 33.3%), A98S/G (n = 4, 27%), H221Y (n = 2, 13%) and P225H (N = 1, 7.5%) mutations were only seen in pre-treated patients. 2014 PloS one Result HIV A98G;A98S;H221Y;P225H;Y181C;Y181I 28;28;49;72;4;4 34;34;54;77;11;11 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. Together with K65R, this mutation is associated with resistance to ddl, ABC, and TDF. 2014 PloS one Result HIV K65R 14 18 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. V75T/M and T69D/N mutations, associated with decreased susceptibilities to d4T and ddI, were detected in 4/22 (18.1%) and 6/22 (27.2%) patients. 2014 PloS one Result HIV T69D;T69N;V75M;V75T 11;11;0;0 17;17;6;6 25174641 Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. pallidum that was tested positive for the A2058G mutation. 2014 Journal of the International AIDS Society Result HIV A2058G 42 48 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. 1 might differentially improve potency against the Y181C-bearing variants of HIV-RT. 2015 Biochimica et biophysica acta Result HIV Y181C 51 56 RT 81 83 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. As was demonstrated in MCPRO simulations of the benzyoxazole inhibitors, the Y181C mutation increases the available space for accommodation of a bulkier R-group. 2015 Biochimica et biophysica acta Result HIV Y181C 77 82 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. Experimentally, the R = Et and i-Pr analogues are equally potent and are both sub-10 nM inhibitors of replication of the Y181C viral strain. 2015 Biochimica et biophysica acta Result HIV Y181C 121 126 PR 33 35 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. Table 2 collects the relative free energies of binding of seven benzyloxazole analogues, for both the wild-type and Y181C mutant, and compares them with previously reported MCPRO (using REST enhanced sampling) and experimental EC50 results. 2015 Biochimica et biophysica acta Result HIV Y181C 116 121 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. Turning to the Y181C mutant, the results from Desmond do indicate that larger alkyl groups are beneficial for activity. 2015 Biochimica et biophysica acta Result HIV Y181C 15 20 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Briefly, we generated a FRET RT construct that allowed us to site-specifically label the fingers (T139C) and thumb (D250C) of p66 with Cy3 and Cy5 dyes (Figure 3C). 2014 Nucleic acids research Result HIV D250C;T139C 116;98 121;103 RT 29 31 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Collectively, these results suggest that, rather than preventing inhibitor binding, K103N enables the inhibitor-bound enzyme to form a polymerase-competent ternary complex by maintaining its grip on the T/P substrate. 2014 Nucleic acids research Result HIV K103N 84 89 Pol 135 145 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Furthermore, K103N RT displayed a similar number of transitions to and from the polymerase-competent ternary complex, both in the absence and presence of EFV (Figure 5G); consequently, kdeparture and karrival were only minimally affected by the inhibitor (Figure 5H). 2014 Nucleic acids research Result HIV K103N 13 18 Pol;RT 80;19 90;21 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Furthermore, the E138D/K101R EFV-RT-T/P complex bound dTTP with dramatically reduced affinity (Figure 3B). 2014 Nucleic acids research Result HIV E138D;K101R 17;23 22;28 RT 33 35 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Furthermore, we found that the binding isotherms for dTTP to the K103N RT-T/P complex were largely similar in the absence and presence of EFV: the Kd value for dTTP binding was only increased 3-fold in the presence of inhibitor (Figure 2C). 2014 Nucleic acids research Result HIV K103N 65 70 RT 71 73 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. However, in the K103N RT-EFV structure solved by Lindberg et al., K103N did not appear to disrupt the K101-E138 salt bridge. 2014 Nucleic acids research Result HIV K103N;K103N 16;66 21;71 RT 22 24 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. However, the FRET histograms for K103N RT-T/P-dNTP were largely identical in the absence and presence of EFV (Figure 5J). 2014 Nucleic acids research Result HIV K103N 33 38 RT 39 41 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. In light of both the available crystal structure and molecular dynamics data, we hypothesized that that the E138-K101 salt bridge may play an important role in the inhibitory activity of EFV toward WT and K103N RT. 2014 Nucleic acids research Result HIV K103N 205 210 RT 211 213 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. In the crystal structure of K103N RT in complex with EFV solved by Ren et al., the K103N substitution was found to disrupt the electrostatic repulsion of K101, and consequently eliminated the salt bridge between K101 and E138 (Figure 2D and Supplementary Movie 1). 2014 Nucleic acids research Result HIV K103N;K103N 28;83 33;88 RT 34 36 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. In the RT-EFV crystal structure, direct contact between EFV and K103 is not observed, and a stereochemical basis for the loss of NNRTI binding due to K103N cannot be inferred from these structures. 2014 Nucleic acids research Result HIV K103N 150 155 NNRTI;RT 129;7 134;9 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Interestingly, the E138D/K101R mutations were found to partially compensate for EFV resistance due to K103N (Table 1). 2014 Nucleic acids research Result HIV E138D;K101R;K103N 19;25;102 24;30;107 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. K103N allows EFV-bound RT to form a polymerase-competent complex. 2014 Nucleic acids research Result HIV K103N 0 5 Pol;RT 36;23 46;25 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. K103N eliminates EFV-induced RT sliding and allows EFV-bound RT to form a polymerase competent complex. 2014 Nucleic acids research Result HIV K103N 0 5 Pol;RT;RT 74;29;61 84;31;63 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. K103N promotes formation of an EFV-bound RT-T/P-dNTP ternary complex. 2014 Nucleic acids research Result HIV K103N 0 5 RT 41 43 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Next, we introduced E138D into the p51 subunit of the FRET RT construct to assess the effect of EFV binding on RT conformation. 2014 Nucleic acids research Result HIV E138D 20 25 RT;RT 59;111 61;113 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Of note, the K103N substitution did not decrease the binding affinity of RPV for the RT-T/P complex (Supplementary Figure S2A and B), an observation which is consistent with the observation that RPV retains activity against this resistance mutation. 2014 Nucleic acids research Result HIV K103N 13 18 RT 85 87 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Taken together, these data provide strong evidence that the EFV-bound K103N RT-T/P can form a stable ternary complex that facilitates phosphodiester bond formation. 2014 Nucleic acids research Result HIV K103N 70 75 RT 76 78 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. The E138D/K101R mutation increased viral susceptibility (as measured by IC50 and EC50) to EFV by up to 7-fold, which appeared to be primarily driven by the E138D mutation (Table 1). 2014 Nucleic acids research Result HIV E138D;E138D;K101R 4;156;10 9;161;15 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. The intensity traces for the K103N-RT-dNTP complex were found to be largely identical in the absence (Figure 5E) and presence (Figure 5F) of EFV. 2014 Nucleic acids research Result HIV K103N 29 34 RT 35 37 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. The K103N substitution in RT is the most commonly reported resistance mutation arising following clinical use of EFV. 2014 Nucleic acids research Result HIV K103N 4 9 RT 26 28 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. These data suggest that K103N does not prevent EFV from binding to the RT-T/P complex but instead allows the inhibitor-bound enzyme to form a stable polymerase-competent ternary complex. 2014 Nucleic acids research Result HIV K103N 24 29 Pol;RT 149;71 159;73 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. This finding provides support for our hypothesis that the K101-E138 salt bridge partially contributes toward the inhibitory activity of EFV toward WT and K103N HIV-1. 2014 Nucleic acids research Result HIV K103N 154 159 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We found that addition of EFV to K103N RT-T/P also resulted in the opening of the fingers and thumb, with a change (Delta) in average Eapp of 0.14 (Figure 5I), similar to the change observed in the WT complex (DeltaEapp = 0.17; Figure 5J). 2014 Nucleic acids research Result HIV K103N 33 38 RT 39 41 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We found that the center of the Eapp distribution decreased from 0.69 for the E138D RT-T/P complex to 0.46 when EFV was added (Figure 3D; Supplementary Table S1). 2014 Nucleic acids research Result HIV E138D 78 83 RT 84 86 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We next assessed the interactions between K103N RT and the T/P substrate. 2014 Nucleic acids research Result HIV K103N 42 47 RT 48 50 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We next introduced K103N into the p66 of the FRET RT construct and assessed the effect of EFV binding on conformational changes in the thumb/fingers. 2014 Nucleic acids research Result HIV K103N 19 24 RT 50 52 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We next quantitatively assessed the effect of K103N on the dynamic interactions between EFV-RT and the T/P substrate using single-molecule assays. 2014 Nucleic acids research Result HIV K103N 46 51 RT 92 94 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We therefore manipulated this electrostatic interaction, engineering a stronger salt bridge by increasing the polarity of the side chains through the introduction of arginine (K101R; pKa change from 10.53 to 12.48) and aspartic acid (E138D; pKa change from 4.25 to 3.65), and evaluated the effect of these substitutions on RT inhibition and virus replication (see the Materials and Methods section). 2014 Nucleic acids research Result HIV E138D;K101R 234;176 239;181 RT 323 325 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. When we quantified NVP and EFV binding to K103N RT, we found that while the K103N substitution decreased NVP binding affinity by ~10-fold (Figure 2A), it surprisingly had no effect on EFV binding (Figure 2B). 2014 Nucleic acids research Result HIV K103N;K103N 42;76 47;81 RT 48 50 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. When we used anisotropy to assess binding to the E138D/K101R RT-T/P complex, we found that EFV bound with increased affinity and induced an even larger change in the maximum r value at saturating inhibitor concentrations (Figure 3A). 2014 Nucleic acids research Result HIV E138D;K101R 49;55 54;60 RT 61 63 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. As a control, we also studied M184V-containing 3TC-resistant viruses and also showed that it results in lower RT levels, in agreement with previous studies. 2014 Viruses Result HIV M184V 30 35 RT 110 112 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. cell-free transmission using DTG-resistant viruses that contained either the R263K, E138K or E138K/R263K mutations. 2014 Viruses Result HIV E138K;E138K;R263K;R263K 84;93;77;99 89;98;82;104 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. The presence of E138K mutation alone caused only slight decreases in GFP expression, both before and after TNF-alpha treatment, and the combination of E138K and R263K mutations together had no additional effect on GFP expression (Figure 2B). 2014 Viruses Result HIV E138K;E138K;R263K 16;151;161 21;156;166 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. The results show that the R263K substitution decreased HIV-1 infectivity, as did the E138K and both the E138K/R263K mutations in tandem that resulted in significant decrease in RT activity. 2014 Viruses Result HIV E138K;E138K;R263K;R263K 85;104;26;110 90;109;31;115 RT 177 179 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. We used also a 3TC/FTC-resistant virus containing a M184V mutation in the RT gene as a control. 2014 Viruses Result HIV M184V 52 57 RT 74 76 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. A patient failing a regimen containing FPV/r and SQV/r developed L363W. 2014 Retrovirology Result HIV L363W 65 70 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Among non-B Gag substitutions, 4 were significantly associated with genotypic PI resistance, of which only A431V was PI-associated in subtype B as well (Table 3). 2014 Retrovirology Result HIV A431V 107 112 Gag;PI;PI 12;78;117 15;80;119 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. As the only PI-associated Gag substitution found in more than one subtype, A431V had a high prevalence in the PI-resistant strains of subtype B (13.5%) and CRF01_AE (18.2%) (Table 3). 2014 Retrovirology Result HIV A431V 75 80 Gag;PI;PI 26;12;110 29;14;112 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Interestingly, of the 21 Gag substitutions observed in our first analysis, K415R and S451G were newly identified to be significantly associated with genotypic PI resistance in subtypes C and B respectively, suggesting a possible involvement in PI-resistance. 2014 Retrovirology Result HIV K415R;S451G 75;85 80;90 Gag;PI;PI 25;159;244 28;161;246 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Longitudinal data from 34 PI-naive patients infected with non-B subtypes revealed the emergence of one Gag substitution (V370A) in a single patient. 2014 Retrovirology Result HIV V370A 121 126 Gag;PI 103;26 106;28 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Our analysis successfully identified the known PI-associated Gag substitution A431V, strengthening the validity of our approach. 2014 Retrovirology Result HIV A431V 78 83 Gag;PI 61;47 64;49 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Particularly, the novel Gag substitutions K415R and S451G were identified in both our longitudinal and cross-sectional sequence analyses. 2014 Retrovirology Result HIV K415R;S451G 42;52 47;57 Gag 24 27 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Patients failing an ATV/r-based regimen developed Gag substitution patterns: P453L or V374A + R387K + S451G + P453Ins. 2014 Retrovirology Result HIV P453L;R387K;S451G;V374A 77;94;102;86 82;99;107;91 Gag 50 53 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Patients failing DRV/r-based regimens developed Gag substitution patterns P453Ins or T427P + R452G. 2014 Retrovirology Result HIV R452G;T427P 93;85 98;90 Gag 48 51 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Some substitutions were from a less to a more common amino acid such as M138L. 2014 Retrovirology Result HIV M138L 72 77 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Specifically, patients failing LPV/r-based regimens developed one of the following Gag substitution patterns: L363W + E477Q, F363L + N389T + P422Q + P455L, K411Q, P472S + P474L, K415R + I469T, M138L, A374T or G420A. 2014 Retrovirology Result HIV A374T;E477Q;F363L;G420A;I469T;K411Q;K415R;L363W;M138L;N389T;P422Q;P455L;P472S;P474L 200;118;125;209;186;156;178;110;193;133;141;149;163;171 205;123;130;214;191;161;183;115;198;138;146;154;168;176 Gag 83 86 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. A62V, an accessory NRTI-associated mutation endemic in Russian AFSU strains, was present in 235 (78%) of 300 subtype A viruses and in one (1.8%) of 55 CRF02_AG viruses (P < 0.001). 2014 AIDS (London, England) Result HIV A62V 0 4 NRTI 19 23 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S occurred alone in 18 patients and with the accessory resistance mutation K101E in 26 patients. 2014 AIDS (London, England) Result HIV K101E;G190S 79;0 84;5 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S occurred with Y181C, K103N, or another NNRTI-resistance mutation in six, three, and two patients, respectively. 2014 AIDS (London, England) Result HIV K103N;Y181C;G190S 27;20;0 32;25;5 NNRTI 45 50 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S was more common in subtype AFSU viruses from the 124 patients receiving efavirenz (n = 48, 39%) than the 43 patients receiving nevirapine (n = 7, 16%; P = 0.008). 2014 AIDS (London, England) Result HIV G190S 0 5 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S was more common in the 167 NNRTI-treated patients with subtype AFSU viruses than the 37 NNRTI-treated patients with CRF02_AG viruses (55/167 vs. 2014 AIDS (London, England) Result HIV G190S 0 5 NNRTI;NNRTI 33;94 38;99 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S was not identified in more than 3000 antiretroviral-naive patients with subtype A viruses including more than 700 patients in FSU countries. 2014 AIDS (London, England) Result HIV G190S 0 5 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S was the most common NNRTI-resistance mutation, occurring in 55 (33%) subtype AFSU viruses from 167 NNRTI-treated patients (Table 2). 2014 AIDS (London, England) Result HIV G190S 0 5 NNRTI;NNRTI 26;105 31;110 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. K101E was the second most common NNRTI-resistance mutation in subtype AFSU viruses, occurring in 24% (n = 40) of viruses from NNRTI-treated patients. 2014 AIDS (London, England) Result HIV K101E 0 5 NNRTI;NNRTI 33;126 38;131 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. M184V/I alone was the most common NRTI-resistance mutation pattern, occurring in 36% (79/218) of patients receiving just thymidine-analog containing regimens (ZDV and/or d4T and 3TC), 23% (14/61) receiving just nonthymidine-analog regimens (abacavir and/or ddI and 3TC), and 14% (12/87) receiving both thymidine-analog and nonthymidine-analog regimens. 2014 AIDS (London, England) Result HIV M184I;M184V 0;0 7;7 NRTI 34 38 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. Of 25 patients with G190S, 16 (35%) were from two studies of 46 patients from FSU countries compared with 9 (1.5%) of 601 patients from the remaining studies (P < 0.001). 2014 AIDS (London, England) Result HIV G190S 20 25 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. Of the 243 patients who received one or more protease inhibitors, 32 (13%) had a study-defined protease inhibitor-resistance mutation most commonly L10F, K20T, V32I, L33F, M46I/L, I47V/A, I50L, F53L, I54V/L, Q58E, L76V, V82A/C, I84V, L89V, and L90M. 2014 AIDS (London, England) Result HIV F53L;I47A;I47V;I50L;I54L;I54V;I84V;K20T;L10F;L33F;L76V;L89V;L90M;M46I;M46L;Q58E;V32I;V82A;V82C 194;180;180;188;200;200;228;154;148;166;214;234;244;172;172;208;160;220;220 198;186;186;192;206;206;232;158;152;170;218;238;248;178;178;212;164;226;226 PR;PR 45;95 53;103 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. One or more of the non-TAMs, K65R/N, L74V/I, and Y115F were present in 1.4% (n = 3), 26% (n = 16), and 9.2% (n = 8) of patients receiving thymidine-analog, nonthymidine-analog, and both thymidine-analog and nonthymidine-analog regimens. 2014 AIDS (London, England) Result HIV K65N;K65R;L74I;L74V;Y115F 29;29;37;37;49 35;35;43;43;54 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The most common NNRTI-resistance mutations in 725 samples from 647 NNRTI-experienced patients with subtype A viruses were K103N (19%), G190A (13%), Y181C (11%), K101E (4.4%), G190S (3.9%), and Y188L (1.7%) (Supplemental Figure 1, http://links.lww.com/QAD/A586). 2014 AIDS (London, England) Result HIV G190A;G190S;K101E;K103N;Y181C;Y188L 135;175;161;122;148;193 140;180;166;127;153;198 NNRTI;NNRTI 16;67 21;72 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The multi-NRTI resistance mutation Q151M occurred in two patients receiving both thymidine-analog and nonthymidine-analog containing regimens. 2014 AIDS (London, England) Result HIV Q151M 35 40 NRTI 10 14 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The next most common NNRTI-resistance mutations in subtype AFSU viruses were K103N (25 patients), Y181C (13 patients), G190A (8 patients), A98G (4 patients), V108I (3 patients), and Y188L (2 patients). 2014 AIDS (London, England) Result HIV A98G;G190A;K103N;V108I;Y181C;Y188L 139;119;77;158;98;182 143;124;82;163;103;187 NNRTI 21 26 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The nonpolymorphic RT mutation, K82R, occurred in 8.0% (24/300) of subtype A viruses, which is higher than its proportion in reverse transcriptase inhibitor (RTI)-naive (10/3072, 0.3%, P < 0.001) and RTI-experienced (2/1042, 0.2%, P < 0.001) patients with subtype A viruses in the Stanford HIVDB. 2014 AIDS (London, England) Result HIV K82R 32 36 RT;RT;RT;RT 125;158;200;19 146;161;203;21 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. To determine the contribution of G190S to acquired and transmitted NNRTI resistance, we examined the prevalence of G190S in NNRTI-experienced and NNRTI-naive patients with subtype A viruses in the Stanford HIVDB. 2014 AIDS (London, England) Result HIV G190S;G190S 33;115 38;120 NNRTI;NNRTI;NNRTI 67;124;146 72;129;151 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. To investigate the high frequency of G190S in subtype AFSU viruses, we examined the codon usage at RT position 190 in HIV-1 sequences in the LANL Database. 2014 AIDS (London, England) Result HIV G190S 37 42 RT 99 101 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. Viruses with GGC require one nucleotide change at the first position (GGC AGC) to develop G190S, whereas viruses with GGA require changes at the first and third positions (GGA AGC). 2014 AIDS (London, England) Result HIV G190S 90 95 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. With the exception of G190S and K101E, there were no differences in the proportions of NNRTI-resistance mutations between subtype AFSU and CRF02_AG. 2014 AIDS (London, England) Result HIV G190S;K101E 22;32 27;37 NNRTI 87 92 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Additionally, as an increased ALIX-binding has been implicated in the formation of the S40F-induced filopodia, we now speculate that ALIX overexpression might regulate this phenomenon by enhancing Gag ubiquitination. 2014 Viruses Result HIV S40F 87 91 Gag 197 200 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Additionally, by this approach we wanted to ensure comparable levels of Pr55 polyprotein as the substrate for ubiquitination, because the PTAP mutation causes a Gag processing defect leading to accumulation of cell associated Pr55, a phenotype which is not observed for the S40F mutant, which shows wt Gag processing except for the CA-SP1 cleavage (Figure 1B). 2014 Viruses Result HIV S40F 275 279 SP1;Gag;Gag;Capsid;PR;PR 336;162;303;333;72;227 339;165;306;335;74;229 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Additionally, we included an S40N mutant as a more conservative exchange for a phosphoseryl residue, which was also chosen by Radestock et al. 2014 Viruses Result HIV S40N 29 33 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. After overnight cocultivation, beta-galactosidase activity was measured by a colorimetric assay, showing that cells expressing DeltaPTAP-SL or S40F-SL mutant were able to induce a clearly enhanced T-cell activation over a broad range of effector-to-target ratios when compared to cells expressing wt Gag-SL (Figure 7D). 2014 Viruses Result HIV S40F 143 147 Gag 300 303 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Again, the level of Gag ubiquitination for the S40F mutant was almost indistinguishable from that observed for the PTAP mutant. 2014 Viruses Result HIV S40F 47 51 Gag 20 23 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Albeit different to the PTAP, the S40F mutant exhibits wt-like virus release. 2014 Viruses Result HIV S40F 35 39 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Altogether, these data demonstrate that the S40F mutant enhances the membrane association of Gag at a rate comparable to a PTAP mutant. 2014 Viruses Result HIV S40F 44 48 Gag 93 96 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Analyses of wt, PTAP or S40F VLPs using the K48-specific antibody demonstrated that even the wt VLPs displays a very weak baseline amount of K48-linked polyubiquitination, that was clearly enhanced when the PTAP or Ser-40 were mutated (Figure 6A). 2014 Viruses Result HIV S40F 25 29 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. As a control, we used the MA G2A mutation, which abrogates the myristoylation of Gag, and, thus, strongly decreases membrane binding, and the PTAP mutant, which was shown previously to exhibit increased amounts of membrane bound Gag. 2014 Viruses Result HIV G2A 29 32 Gag;Gag;Matrix 81;230;26 84;233;28 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. As in this experimental setting the turnover of polyubiquitinated Gag by either the 26S proteasome or deubiquitinating enzymes is prevented, also the formation of ubiquitinated Gag species was observed in the wt situation, although at much lower level, approximately 10%-20% of the Gag-ubiquitin adducts detected for S40F and PTAP as measured by densitometry (Figure 2C). 2014 Viruses Result HIV S40F 317 321 Gag;Gag;Gag 66;177;282 69;180;285 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. By using this method, elaborated previously for the PTAP mutant, we wanted to investigate whether the S40F mutation, which clearly increases K48-linked polyubiquitination, also enhances the entry of Gag into the MHC-I pathway. 2014 Viruses Result HIV S40F 103 107 Gag 200 203 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Calculation of the ratio between membrane (fractions 1 and 2) and cytoplasmic (fraction 4) Gag from four independent experiments revealed a significant 1.75-fold increase of membrane associated Gag for the S40F mutant when compared to wt protein or the S40D and S40N mutants (Figure 4C). 2014 Viruses Result HIV S40D;S40F;S40N 253;206;262 257;210;266 Gag;Gag 91;194 94;197 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Consistent with previous findings, ALIX overexpression efficiently restored the VLP release of the PTAP and the S40F/ PTAP mutants, whereas the wt and the S40F mutant were not affected (Figure 5A, compare lanes 4 with 5 and 8 with 9). 2014 Viruses Result HIV S40F;S40F 113;156 117;160 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Consistently, the S40F/ PTAP-SL double mutant even revealed the strongest effect on SL presentation (Figure 7A). 2014 Viruses Result HIV S40F 18 22 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Even when the budding defect and, thus, the accumulation of cell associated Gag was taken into account, analyses of three independent experiments revealed an approximately threefold increase in SL-presentation when the PTAP-SL or S40F-SL variant were compared to wt Gag-SL (Figure 7B). 2014 Viruses Result HIV S40F 231 235 Gag;Gag 76;267 79;270 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. First in vitro evidence that in HIV-1 expressing cells the introduction of the S40F mutation somehow increases the amount of Pr55 in membrane associated assembly compartments was reported previously. 2014 Viruses Result HIV S40F 79 83 PR 125 127 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Flow cytometry using the mAb 25D1.16, which specifically recognizes H2-Kb-bound SL, revealed that cells expressing PTAP-SL or S40F-SL displayed higher numbers of H2-Kb-SL complexes at the cell surface when compared to cells expressing wt Gag-SL (Figure 7A). 2014 Viruses Result HIV S40F 127 131 Gag 239 242 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Furthermore, these results confirm that these K48-linked polyubiquitinated Gag species even participate in Gag assembly process for all variants, wt, PTAP, S40F, though at different levels. 2014 Viruses Result HIV S40F 157 161 Gag;Gag 75;107 78;110 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. HeLa cells stably expressing the murine MHC-I allotype H2-Kb (HeLa-Kb,) were transfected with expression plasmids coding for Gag-SL, PTAP-SL, S40F-SL and S40F/ PTAP-SL. 2014 Viruses Result HIV S40F;S40F 143;155 147;159 Gag 125 128 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. However, analyses of the cell-associated Gag ubiquitination revealed that none of the conservative mutants, S40N or S40D, can increase Gag ubiquitination as it was observed for the S40F mutant (Figure 3A). 2014 Viruses Result HIV S40D;S40F;S40N 116;181;108 120;185;112 Gag;Gag 41;135 44;138 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. However, in case of the S40D mutant the resulting Phe to Arg mutation in position 56 in the Pol-protein could not be introduced in the context of the wt p6 sequence due to constraints of the codon usage and the overlapping ORFs. 2014 Viruses Result HIV F56R;S40D 50;24 84;28 Pol;Gag 92;153 95;155 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. However, in the context of the Y36A/S40F double mutant, the Y36A mutation reverts the ubiquitination phenotype induced by the S40F mutation. 2014 Viruses Result HIV S40F;S40F;Y36A;Y36A 36;126;31;60 40;130;35;64 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In consistency with previously reported surface plasmon resonance analyses, only the mutant S40F, but none of the conservative mutations S40D and S40N, increases the membrane associtation of Gag when compared to wt (Figure 4A). 2014 Viruses Result HIV S40D;S40F;S40N 137;92;146 141;96;150 Gag 191 194 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In consistency, Western blot analyses revealed that the S40A mutation had, as for the S40N and S40D mutations, no obvious impact on ubiquitination of Gag (Figure 3B). 2014 Viruses Result HIV S40A;S40D;S40N 56;95;86 60;99;90 Gag 150 153 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In correlation with the analysis of the Gag ubiquitination by Western blot (Figure 7C) and the MHC-I antigen presentation (Figure 7A,B), the S40F/ PTAP-SL mutant displayed the highest potential to activate T cells in vitro. 2014 Viruses Result HIV S40F 141 145 Gag 40 43 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In order to investigate whether or not there is any correlation between the efficiency of virus release or the increased ALIX binding and Gag ubiquitination, we co-transfected HeLa cells with p R wt, the S40F and PTAP mutants, as well as a S40F/ PTAP double mutant, with or without ALIX expression plasmids. 2014 Viruses Result HIV S40F;S40F 204;241 208;245 Gag 138 141 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Introduction of the S40F mutation into the psyngag background enhances the Gag ubiquitination at a similar rate when compared to the situation when Gag was expressed in the context of the HIV-1 genome (Figure 2B). 2014 Viruses Result HIV S40F 20 24 Gag;Gag 75;148 78;151 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Later, it was reported by others that this S40F mutation induces filopodia-like membrane protrusions harboring Gag. 2014 Viruses Result HIV S40F 43 47 Gag 111 114 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Moreover, a recent study implicated a possible link between the S40F mutation and syntenin, a protein which was characterized to bind polyubiquitin irrespectively of the linkage type. 2014 Viruses Result HIV S40F 64 68 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Moreover, the respective S40F/ PTAP double mutant shows an about two-fold increase in ubiquitination compared to the respective single mutants which might even indicate an additive effect of the S40F and PTAP mutations on Gag ubiquitination (Figure 5B). 2014 Viruses Result HIV S40F;S40F 25;195 29;199 Gag 223 226 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Next, we wanted to investigate the consequences of ALIX overexpression on Gag ubiquitination, which was demonstrated to restore virus release of PTAP-deficient Gag mutants while being inactive on release of the S40F mutant. 2014 Viruses Result HIV S40F 211 215 Gag;Gag 74;160 77;163 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. observed the formation of filopodia-like structures for the S40F mutant especially in the context of unprocessed Gag, we employed a PR-deficient subgenomic HIV-1 expression construct that harbors an inactive RT and a primer binding site deletion (p R PR-). 2014 Viruses Result HIV S40F 60 64 Gag;PR;PR;RT 113;132;251;208 116;134;253;210 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Our suspicion that this phenomenon is somehow specific for S40F, was further supported by recent finding from Watanabe et al., demonstrating that the S40A mutant displays wt CA-SP1 processing. 2014 Viruses Result HIV S40A;S40F 150;59 154;63 SP1;Capsid 177;174 180;176 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Quantification of the amount of CA in the VLP fraction versus the total amount of Gag confirmed the previously reported wild type efficiency for virus release of the S40F mutant (Figure 1C). 2014 Viruses Result HIV S40F 166 170 Gag;Capsid 82;32 85;34 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Quantification of the band intensities revealed that the S40F mutant exhibits a distribution of Gag within the gradient which is comparable to that of the PTAP mutant (Figure 4B). 2014 Viruses Result HIV S40F 57 61 Gag 96 99 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Recently, we and others reported that specific mutation of the highly conserved serine 40 to phenylalanine (S40F) within p6 leads to impaired CA-SP1 processing resulting in an abnormal core morphology and thus in a reduced replication capacity, whereas virus release and binding of ALIX to p6 were not reduced. 2014 Viruses Result HIV S40F;S40F 108;80 112;106 SP1;Gag;Gag;Capsid 145;121;290;142 148;123;292;144 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Results shown in Figure 2A confirm that the ladder observed for the S40F mutant consists of ubiquitinated Gag species and that this modification occurs to a similar extent as for the PTAP mutant. 2014 Viruses Result HIV S40F 68 72 Gag 106 109 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. S40F, but none of the conservative exchanges, induces the phenotype described above. 2014 Viruses Result HIV S40F 0 4 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Since Ser-40 in p6 can only be exchanged to Phe without disturbing the amino acid sequence encoded by the overlapping pol-ORF, the p6 S40N mutation results in a Phe to Gln exchange in position 56 in the Pol-protein. 2014 Viruses Result HIV F56Q 161 195 Pol;Pol;Gag;Gag 118;203;16;131 121;206;18;133 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Substitution of Ser-40 with Phe did not change the position or number of residues included in the C-terminal helix compared with wt sp6(23-52), and their structures appear to be even similar. 2014 Viruses Result HIV S40F 16 31 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. that Gag alone is sufficient for the formation of S40F-induced filopodia. 2014 Viruses Result HIV S40F 50 54 Gag 5 8 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The conservative mutations S40D and S40N did not provide any observable effect on the secondary structure, which like the S40F mutation, resemble that of wt sp6(23-52) (Figure 8). 2014 Viruses Result HIV S40D;S40F;S40N 27;122;36 31;126;40 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The Non-Conservative Amino Acid Exchange S40F, but Not the Conservative Substitutions S40D or S40N, Induces Elevated Gag Ubiquitination. 2014 Viruses Result HIV S40D;S40F;S40N 86;41;94 90;45;98 Gag 117 120 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The observation of NHi - NHi+1, NHi - NHi+2, alphaHi - NHi+2, alphaHi - NHi+3, alphaHi - NHi+4 and alphaHi - betaHi+3 NOEs, which are indicative of helical secondary structure, showed that, similarly to wt sp6(23-52), the mutant sp6(23-52)S40F has a preference for an alpha-helical structure involving residues Ile-31 to Asp-48 under hydrophobic membranous conditions (50% aqueous trifluorethanol (TFE) solution). 2014 Viruses Result HIV S40F 239 243 Asp 321 324 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The previously reported CA-SP1 processing defect of the S40F mutant is visible upon shorter exposure of the Western blot membrane (Figure 1A,B, lower panels). 2014 Viruses Result HIV S40F 56 60 SP1;Capsid 27;24 30;26 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F Mutation Creates a Hydrophobic Domain Involving Aromatic Residues Tyr-36 and Phe-40 at the Same Surface of the C-Terminal Helix of p6. 2014 Viruses Result HIV S40F 4 8 Gag 140 142 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F Mutation Enhances MHC-I Antigen Presentation of Gag. 2014 Viruses Result HIV S40F 4 8 Gag 57 60 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F Mutation Increases the Amount of Membrane Associated Gag. 2014 Viruses Result HIV S40F 4 8 Gag 62 65 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F Mutation Increases the K48-Linked Polyubiquitination of Gag. 2014 Viruses Result HIV S40F 4 8 Gag 65 68 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F/ PTAP-SL exhibits an even more pronounced, approximately fivefold increase in SL-presentation in comparison to wt Gag-SL. 2014 Viruses Result HIV S40F 4 8 Gag 123 126 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The same analyses of virus like particle (VLP) preparations displayed a very similar pattern of high molecular weight species of Gag for the S40F but not for the wt VLPs (Figure 1B). 2014 Viruses Result HIV S40F 141 145 Gag 129 132 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Therefore, the S40F mutant exhibits Gag ubiquitination independently of Gag processing or other HIV-1 proteins, and this ubiquitination occurs to an extent in cell and VLP fraction that is comparable to that of the PTAP mutant. 2014 Viruses Result HIV S40F 15 19 Gag;Gag 36;72 39;75 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Therefore, we wanted to investigate what kind of polyubiquitination is induced by the S40F mutation. 2014 Viruses Result HIV S40F 86 90 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. This notion is further supported by the observation that the S40F mutant, which exhibits wt virus release efficiency, becomes ubiquitinated like the release-deficient PTAP mutant (Figure 5). 2014 Viruses Result HIV S40F 61 65 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. This was confirmed by a comparison of plots of the alpha-proton chemical shifts relative to those of random coil values (Figure 8), which indicates that the substitution of Ser-40 with Phe slightly stabilizes the region of the C-terminal helix comprised of residues Leu-41 to Leu-44, proximal to Phe-40. 2014 Viruses Result HIV S40F 173 188 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Thus, CA-SP1 processing, virus maturation, membrane interaction, and Gag ubiquitination appear to be connected to each other, inasmuch as only the S40F, but none of the investigated conservative mutations, influence those processes. 2014 Viruses Result HIV S40F 147 151 SP1;Gag;Capsid 9;69;6 12;72;8 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Thus, the S40F mutation creates a hydrophobic domain involving the bulky aromatic residues Tyr-36 and Phe-40, which may account for the observed increased membrane affinity of the S40F mutant. 2014 Viruses Result HIV S40F;S40F 10;180 14;184 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Thus, these sensitive immunological methods underline that both, PTAP deletion and mutation of Ser-40 with Phe, act independently of each other, but can also exert an additive effect on the K48-linked polyubiquitination of Gag and, consequently, on its entry into the UPS. 2014 Viruses Result HIV S40F 95 110 Gag 223 226 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Thus, we conclude that the enhanced Gag ubiquitination of the S40F mutant, like the formation of the filopodia-like structures and the defective CA-SP1 processing, represents most probably a Phe specific phenomenon. 2014 Viruses Result HIV S40F 62 66 SP1;Gag;Capsid 148;36;145 151;39;147 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Thus, we investigated the impact of the S40F mutation on the intracellular distribution of Gag in PR-deficient context by membrane flotation, an established method that has been previously applied to address the membrane binding properties of Gag mutants. 2014 Viruses Result HIV S40F 40 44 Gag;Gag;PR 91;243;98 94;246;100 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. To ascertain whether the S40F, S40N or S40D mutations alter the C-terminal helix of p6, the synthetic peptides (s)p6(23-52)S40F, (s)p6(23-52)S40D and (s)p6(23-52)S40N were characterised by 1H NMR spectroscopy. 2014 Viruses Result HIV S40D;S40F;S40N;S40D;S40F;S40N 141;123;162;39;25;31 145;127;166;43;29;35 Gag;Gag;Gag;Gag 84;114;132;153 86;116;134;155 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. To confirm that the Tyr-36 plays a crucial role in the formation of the hydrophobic patch in Gag-expressing cells, we examined the Gag ubiquitination of the Y36A mutant, carrying an exchange in position 36 from Tyr to Ala, and the Y36A/S40F double mutant (Figure 9B). 2014 Viruses Result HIV S40F;Y36A;Y36A;Y36A 236;157;231;203 240;161;235;221 Gag;Gag 93;131 96;134 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. To investigate if the S40F mutation enhances the immunogenicity of Gag, we tested the ability of HeLa-Kb cells expressing Gag-SL wt, PTAP-SL, S40F-SL or S40F/ PTAP-SL to activate B3Z hybridoma T cells. 2014 Viruses Result HIV S40F;S40F;S40F 22;143;154 26;147;158 Gag;Gag 67;122 70;125 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. To investigate whether the S40F mediated Gag ubiquitination occurs independently of other viral proteins, we compared the S40F and PTAP mutants in context of a codon optimized synthetic gag gene expressed from a CMV promoter driven expression plasmid (psyngag). 2014 Viruses Result HIV S40F;S40F 27;122 31;126 Gag;Gag 41;187 44;190 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. To more directly analyze a potential correlation between phosphorylation and ubiquitination, we established an S40D mutant in the context of the HIV-1 NL4-3 proviral clone. 2014 Viruses Result HIV S40D 111 115 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. To more precisely ensure our findings concerning the S40F mutant, we sought to use another read out system for the extent of K48-linked polyubiquitination which is the presentation of Gag derived epitopes in the context of MHC-I molecules at the cell surface. 2014 Viruses Result HIV S40F 53 57 Gag 184 187 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. To rationalize the increased membrane association caused by the S40F mutation, the structure of sp6(23-52)S40F was calculated based on the assigned crosspeaks observed in the 2D 1H NOESY spectrum. 2014 Viruses Result HIV S40F;S40F 106;64 110;68 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Western blot analyses of HeLa cell lysates derived from cells transfected with the subgenomic HIV-1 expression construct pNLenv1 directing the expression of wt and the S40F mutant reveal a ladder of bands migrating above Pr55 for the S40F mutant, which are reminiscent of ubiquitinated Gag species (Figure 1A). 2014 Viruses Result HIV S40F;S40F 168;234 172;238 Gag;PR 286;221 289;223 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Western blot analyses revealed that the Y36A mutant alone reveals no impact on the Gag ubiquitination when compared to wt Gag. 2014 Viruses Result HIV Y36A 40 44 Gag;Gag 83;122 86;125 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. A concentration of 180 muM that was 10,000 times above the IC50 of 7.8 nM (as determined in an assay of cell-free infection with WT virus) was needed to delay G367R reversion (Figure 4b). 2014 Virology journal Result HIV G367R 159 164 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. A gp120 binding inhibitor DS003 and a CXCR4 inhibitor AMD3100 were used in MT2 cultures infected by G367R viruses pseudotyped with VSV-G. 2014 Virology journal Result HIV G367R 100 105 gp120 2 7 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. A low concentration of PMA of 0.1 ng/ml or ionomycin at 25 ng/ml both inhibited the G367R reversion. 2014 Virology journal Result HIV G367R 84 89 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Again, there was no growth or reversion of G367R in MT4 cells, suggesting that a different mechanism of reversion of G367R may be involved in different cells.However, PMA and ionomycin inhibited the reversion of G367R virus in both MT2 and SupT1 cells (Figure 6b). 2014 Virology journal Result HIV G367R;G367R;G367R 43;117;212 48;122;217 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. As shown above, coculturing G367R positive 293 T and TZM-bl cells, but not their supernatants, with MT2 or MT4 cells confirmed that the cell-associated the G367R virus can infect MT2 cells and revert to WT but cannot infect MT4 cells (Table 4). 2014 Virology journal Result HIV G367R;G367R 28;156 33;161 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Based on the above results, G367R reversion may be determined by undefined cellular mechanisms. 2014 Virology journal Result HIV G367R 28 33 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Contrary to expectations, we found that IL2 was able to inhibit the reversion of G367R virus in MT2 cells at the same concentration used to maintain T lymphocyte growth (Figure 6a) without affecting cell viability, while it only slightly inhibited cell-free wt HIV by about 2 fold (data not shown). 2014 Virology journal Result HIV G367R 81 86 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Endocytosis inhibitors can delay G367R reversion. 2014 Virology journal Result HIV G367R 33 38 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Entry inhibitors can delay G367R reversion. 2014 Virology journal Result HIV G367R 27 32 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Figure 1 shows that the increase in p24 in the G367R-infected samples was slower than occurred when WT virus was used to mediate infection. 2014 Virology journal Result HIV G367R 47 52 p24 36 39 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Finally, supporting evidence comes from results obtained with 293 T and TZM-bl cells that were infected by VSV-G pseudotyped G367R virus and then cocultured with MT2 or MT4 cells. 2014 Virology journal Result HIV G367R 125 130 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. First, MT2 cells were directly transfected with the G367R proviral plasmid instead of by infection. 2014 Virology journal Result HIV G367R 52 57 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Four T cell lines, MT2, MT4, SupT1 and PM-1, were used to investigate the mechanism(s) whereby G367R can achieve reversion. 2014 Virology journal Result HIV G367R 95 100 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. HIV binding to the viral receptor and coreceptor can trigger viral fusion with the plasma membrane; however, the G367R mutant might have lost this ability. 2014 Virology journal Result HIV G367R 113 118 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. However, DS003 was able to inhibit G367R reversion at concentrations of 20 nM and 200 nM, since the p24 values in culture supernatants increased by day 14 and then decreased. 2014 Virology journal Result HIV G367R 35 40 p24 100 103 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. However, phenotypic reversion did occur in the G367R positive TZM-bl cells that were maintained for up to 10 weeks in culture, since both supernatants and cocultures were infectious at the time points that were tested (Table 4). 2014 Virology journal Result HIV G367R 47 52 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. However, we found higher reversion rates than expected when we employed the defective G367R virus that was pseudotyped with VSV-G and then used to infect MT2 cells (Figure 1 and Table 1). 2014 Virology journal Result HIV G367R 86 91 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. In contrast, G367R alone (i.e., not pseudotyped) was noninfectious (Figure 1), consistent with our previous report. 2014 Virology journal Result HIV G367R 13 18 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. In contrast, IL2 had no influence on the reversion of G367R in SupT1 cells, based on both p24 measurements and CPE (Figure 6a). 2014 Virology journal Result HIV G367R 54 59 p24 90 93 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. In contrast, MT4 cells that were cocultured with G367R positive 293 T or TZM-bl cells did not develop CPE over a 4 week period. 2014 Virology journal Result HIV G367R 49 54 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. In order to explore whether the spread of the G367R mutant virus might be affected by inhibitors of endocytosis, we employed three such molecules in our experiments, i.e., chlorpromazine which is thought to inhibit clathrin-dependent (CDE) processes as well as two clathrin-independent endocytosis(CIE) inhibitors, i.e., Genistein and methyl-beta-cyclodextrin (MbetaCD). 2014 Virology journal Result HIV G367R 46 51 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. In our experiments, CPE appeared after about 3 weeks in cocultures of MT4 cells containing G367R provirus, i.e., MT4 donor cells with uninfected MT2 cells. 2014 Virology journal Result HIV G367R 91 96 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Interleukin 2, PMA and ionomycin can block G367R reversion differentially in varying T cell lines. 2014 Virology journal Result HIV G367R 43 48 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Moreover, it can be concluded that the efficiency of the G367R reversion is completely determined by the type of target cell used and not by donor cells. 2014 Virology journal Result HIV G367R 57 62 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. MT2 cells cocultured with the G367R positive 293 T or TZM-bl cells developed CPE within about 1-2 weeks while the cells infected by G367R positive supernatants did not. 2014 Virology journal Result HIV G367R;G367R 30;132 35;137 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Next, we investigated whether donor or target cells determine the efficiency of reversion of the G367R mutant. 2014 Virology journal Result HIV G367R 97 102 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Only one or two subtoxic concentrations of chlorpromazine and MbetaCD as tested in 2-fold serial dilutions permitted cell growth yet inhibited G367R virus replication (Figure 5). 2014 Virology journal Result HIV G367R 143 148 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Reversion in the G367R transfected MT2 cells was comparable in terms of time required to that of infection by the VSV-G pseudotyped G367R mutant, indicating that reversion does not seem to be influenced by the VSV-G protein. 2014 Virology journal Result HIV G367R;G367R 17;132 22;137 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Sequencing of the env gene in all the reverted MT2 and SupT1 cells, regardless the number of infected cells that were seeded demonstrating that G367R had reverted from GGA AGG GAC CCA to GGA GGG GAC CCA, corresponding to a change in amino acid sequence from GRDP to GGDP within the CD4 binding site (Table 3). 2014 Virology journal Result HIV G367R 144 149 Env 18 21 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Similar results to those obtained with PM-1 cells were obtained with both Jurkat cells, CEM cells and CBMCs when infected by the G367R mutant pseudotyped with VSV-G (data not shown). 2014 Virology journal Result HIV G367R 129 134 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Taking together, it appears that G367R reversion requires the entry of the G367R mutant into cells and that replication must precede reversion. 2014 Virology journal Result HIV G367R;G367R 33;75 38;80 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The env mutant G367R is defective in cell-free infection but can replicate and revert to wild type spontaneously in the MT2 infected T cell line. 2014 Virology journal Result HIV G367R 15 20 Env 4 7 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The fact that MT4 cells infected by diluted G367R viruses that were pseudotyped with VSV-G did not revert is also in agreement with this result (Table 2). 2014 Virology journal Result HIV G367R 44 49 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The fact that SupT1 cells infected by G367R pseudotyped with VSV-G reverted in the same manner as seen with infection of MT2 cells negates the likelihood that the HTLV-1 in the MT2 cells contributed to the reversion. 2014 Virology journal Result HIV G367R 38 43 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The G367R reversion is both cell-type dependent and viral infection dose-dependent. 2014 Virology journal Result HIV G367R 4 9 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The G367R reversion is facilitated by viral transmission between cells. 2014 Virology journal Result HIV G367R 4 9 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The growth curves and extent of CPE of G367R mutated virus in each of MT2, MT4, SupT1 and PM-1 cells are displayed in Figure 2 and in Table 1. 2014 Virology journal Result HIV G367R 39 44 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The initial infection of MT4 by pseudotyped G367R was successful on the basis of p24 value but viral replication then decreased gradually while PM-1 cells were not as sensitive to infection as MT4 or MT2 cells (Figure 2). 2014 Virology journal Result HIV G367R 44 49 p24 81 84 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The results show that reversion of G367R was cell-type dependent, with reversion occurring very frequently in both MT2 and SupT1 cells but rarely in MT4 and PM-1 cells (Tables 1 and 2). 2014 Virology journal Result HIV G367R 35 40 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The results showed that DS003 was not able to inhibit G367R reversion when used at a fairly low concentration. 2014 Virology journal Result HIV G367R 54 59 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The spontaneous reversion of G367R mutant involves cell-to-cell transmission and the efficiency of reversion is determined by the type of target cell employed. 2014 Virology journal Result HIV G367R 29 34 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. There was no reversion in MT4 cells when diluted pseudotyped G367R was used to initiate infection. 2014 Virology journal Result HIV G367R 61 66 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. These findings indicate that reversion of the mutant G367R virus is unlikely to be generated over a single round of infection and that multiple rounds of viral replication may be needed in order to increase the chances for a revertant to emerge. 2014 Virology journal Result HIV G367R 53 58 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. These results indicate that the spread of the G367R mutant requires the process of endocytosis and is related to CDE but not to CIE, similar to WT HIV, because this process was not inhibited by MbetaCD and was not affected as much as Genistein-mediated inhibition of cellular replication. 2014 Virology journal Result HIV G367R 46 51 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. These results suggest that the reversion of G367R that is dependent on transmission between cells may be protein kinase C (PKC) related. 2014 Virology journal Result HIV G367R 44 49 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. This finding also indicates that the mutant G367R HIV-1 cannot transmit if MT4 cells serve as both donor and target cells, as p24 values decreased gradually (Figure 3). 2014 Virology journal Result HIV G367R 44 49 p24 126 129 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. This indicates that G367R mutant virus can infect or reinfect TZM-bl cells but cannot infect 293 T cells. 2014 Virology journal Result HIV G367R 20 25 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. This result indicates that the type of target cell is important in determining the reversion of G367R mutant. 2014 Virology journal Result HIV G367R 96 101 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Thus, the G367R mutant has no deficit in ability to bud from MT4 cells. 2014 Virology journal Result HIV G367R 10 15 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Thus, the reversion rate of G367R seems higher than the RT error rate over a single round of infection. 2014 Virology journal Result HIV G367R 28 33 RT 56 58 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. We previously reported that viruses containing the env mutant G367R are defective in cell-free infection, similar to what has been observed for a mutation at position 368, D368R. 2014 Virology journal Result HIV D368R;G367R 172;62 177;67 Env 51 54 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. M184I/V mutations abruptly decreased in the year 2009. 2014 PloS one Result HIV M184I;M184V 0;0 7;7 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of M184I/V mutations (p 0.0004). 2014 PloS one Result HIV M184I;M184V 195;195 202;202 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. The logistic regression model, logit(M184I/V)~beta0 + beta1x lamivudine + beta2 x emtricitabine, controlled for the presence of lamivudine, implemented a lag time of two years between mutation and prescription prevalence, and accounted for overdispersion. 2014 PloS one Result HIV M184I;M184V 37;37 44;44 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. The most common primary mutations associated with ARV resistance in TE individuals ( Figure 2 ) were NRTIs: M184I/V (51.1%) and thymidine analog mutations (TAM) from TAM1 pathway (41L/210W/215Y; 17%), representing 76.2% of all TAM pathways (data not shown); NNRTIs: K103N (24.9%); PIs: L90 M (21.1%), V82 (16.8%), M46I/L (18.2%). 2014 PloS one Result HIV K103N;L90M;M184I;M184V;M46I;M46L 266;286;108;108;314;314 271;291;115;115;320;320 NNRTI;NRTI;PI 258;101;281 264;106;284 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. The slope parameter beta2 was estimated to be -0.021 (p 0.0004) and reflects the strength of association between M184I/V and emtricitabine co-formulations. 2014 PloS one Result HIV M184I;M184V 114;114 121;121 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. We observed a decrease in the frequency of the drug resistance mutations M184I/V over time ( Figure 4 ). 2014 PloS one Result HIV M184I;M184V 73;73 80;80 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. DR mutations were found at codons M41L (n = 22), K65R (n = 3), K70R (n = 10), K103N (n = 7), M184V (n = 21) and T215Y/F (n = 22) in 40 specimens (Table 2). 2014 PloS one Result HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y 78;49;63;93;34;112;112 83;53;67;98;38;119;119 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. Fourteen specimens had a G2748A mutation that led to D67N, a thymidine analogue mutation. 2014 PloS one Result HIV D67N;G2748A 53;25 57;31 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. The nucleotide position of A2723G, A2747G and C2750T were frequent polymorphism for the wild type amino acid K65, K66 and D67, respectively. 2014 PloS one Result HIV A2723G;A2747G;C2750T 27;35;46 33;41;52 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. We synthesized two additional wild-type oligoprobes (K70K-AAA-2 and T215T-ACC-2), since the original oligobeads (K70K-AAA-1 and T215T-ACC-1) gave marginal signals in some specimens (Table 1 and. 2014 PloS one Result HIV K70K;K70K;T215T;T215T 53;113;68;128 57;117;73;133 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Among the East-Africans who had migrated to Sweden, AS-PCR identified minor NNRTI mutations in two patients (3.6%); one female with Y181C and one male with K103N (Table 2). 2014 PloS one Result HIV K103N;Y181C 156;132 161;137 NNRTI 76 81 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. AS-PCR detected Y181C in five females and one male among the 92 (6.5%) Ethiopian patients from Addis Ababa (Table 2). 2014 PloS one Result HIV Y181C 16 21 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Direct sequencing identified additional TDR in two patients: T215S and L90M, respectively. 2014 PloS one Result HIV L90M;T215S 71;61 75;66 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Direct sequencing identified two patients with additional DRM (L100IL, M46L) (Table 2). 2014 PloS one Result HIV L100I;L100L;M46L 63;63;71 69;69;75 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. From replicates of two independent experiments, a conservative accuracy of mutant HIV-1 variants was found to be 0.1% for K103N (AAC and AAT), and 0.25% for Y181C (TGT). 2014 PloS one Result HIV K103N;Y181C 122;157 127;162 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. In none of these patients, the K103N was detected. 2014 PloS one Result HIV K103N 31 36 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. In the Caucasian patients, AS-PCR detected Y181C in two male patients (4.5%) with a proportion of 3.0% and 10.3%, respectively (Table 2). 2014 PloS one Result HIV Y181C 43 48 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. No K103N was detected. 2014 PloS one Result HIV K103N 3 8 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Of these, two had M184V, two had NNRTI mutations (K101E, Y188L) and one had a PI mutation (N88S). 2014 PloS one Result HIV K101E;M184V;N88S;Y188L 50;18;91;57 55;23;95;62 NNRTI;PI 33;78 38;80 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The proportion of Y181C ranged from 0.25% to 4.5% (Figure 3). 2014 PloS one Result HIV Y181C 18 23 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The proportion of Y181C was 0.8% and K103N 17.5%, respectively. 2014 PloS one Result HIV K103N;Y181C 37;18 42;23 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. According to Figure 7B, it is observed that the van der Waals interactions of I47V, V32'I and V82'I in PR2 with APV are decreased by 1.42, 1.37 and 0.49 kcal mol-1 relative to PR1, respectively. 2014 Scientific reports Result HIV I47V 78 82 PR;PR 103;176 106;179 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. also proves that the mutation I50V of PR1 results in the decrease of the distance between I50'Calpha and D25'Calpha, which basically agrees with our studies here. 2014 Scientific reports Result HIV I50V 30 34 PR 38 41 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. As shown from Figure 7B, the residues involving the increase of the van der Waals interaction in PR2 are V32I, V82I, D29', D30' and I84' compared to PR1. 2014 Scientific reports Result HIV V32I;V82I 105;111 109;115 PR;PR 97;149 100;152 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. As shown in Figure 7A, the van der Waals interactions of the mutated residues V32I, I47V, V32'I and I47'V in PR2 with DRV are decreased by 0.49, 0.86, 0.69 and 0.26 kcal mol-1 compared to PR1, respectively. 2014 Scientific reports Result HIV I47V;V32I 84;78 88;82 PR;PR 109;188 112;191 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. By comparing Figure 9E and G to Figure 9A and C, it is found that the distance of the carbon atoms between the alkyls of V32I and V82I in PR2 and the hydrophobic groups (the aniline and Phenyl) of APV are obviously shortened, which correspondingly strengthens the van der Waals interactions of V32I and V82I with APV. 2014 Scientific reports Result HIV V32I;V32I;V82I;V82I 121;294;130;303 125;298;134;307 PR 138 141 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. Figure 7A suggests that the mutation V82I strengthens the van der Walls interaction with DRV, which is in agreement with the shortened distance between the carbon atoms in phenyl of DRV and the alkyl of V82I in PR2 (Figure 8C and G). 2014 Scientific reports Result HIV V82I;V82I 37;203 41;207 PR 211 214 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. Mutations that confer major resistance in PR1, such as G48V, L63P and I84V weaken or do not present these interactions, which basically agrees with our studies here. 2014 Scientific reports Result HIV G48V;I84V;L63P 55;70;61 59;74;65 PR 42 45 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. Previous studies have proved that the above regions in PR2 have three key mutations V32I, I47V and V82I. 2014 Scientific reports Result HIV I47V;V32I;V82I 90;84;99 94;88;103 PR 55 58 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. The difference in motion modes induced by inhibitor bindings may owe to the one in sequence of PR1 and PR2, which involve three key mutations V32I, I47V and V82I. 2014 Scientific reports Result HIV I47V;V32I;V82I 148;142;157 152;146;161 PR;PR 103;95 106;98 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. The previous studies proved that one key mutation (I47V) harbors in the flaps and beta strands of PR2, which may be responsible for the difference in the motion modes of the flaps between PR1 and PR2. 2014 Scientific reports Result HIV I47V 51 55 PR;PR;PR 98;196;188 101;199;191 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. The reason led to this result may be the conformation change induced by the mutation V47I in PR2. 2014 Scientific reports Result HIV V47I 85 89 PR 93 96 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. This result agrees well with the increase in the distances of the carbon atoms between the alkyls of I47V, V32'I and V82'I in PR2 and the hydrophobic groups in APV (Figure 9). 2014 Scientific reports Result HIV I47V 101 105 PR 126 129 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Additionally, the TAT C31C and C31S groups did not differ significantly in terms of CD4 count (t= -1.68, p =.096, SE= 24.47), Log10 viral load (t= .331, p=0.741, SE=.179) or time since diagnosis (t=.394, p=0.694 SE=4.47). 2014 Journal of neurovirology Result HIV C31C;C31S 22;31 26;35 Tat 18 21 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Among HIV seropositive individuals for whom data were available pertaining to the presence of the TAT C31S substitution (n = 179), there were no significant differences between those with and without the substitution with respect to average years of age (t = 0.79, p =.427, beta = 0.66, SE = 0.93), years of education (t = 1.47, p = .144, beta = 0.37, SE = 0.27), and sex [chi2(1) = 0.81, p = .369] The means (and percentage female) for each group are given in Table 1. 2014 Journal of neurovirology Result HIV C31S 102 106 Tat 98 101 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Considering only the HIV-positive group, the C31C group had a significantly higher mean score on the CES-D (n=118 m=5.81 sd=5.81) compared to the C31S group (n=42 m=4.79 sd=3.65). 2014 Journal of neurovirology Result HIV C31C;C31S 45;146 49;150 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Alteration of LEDGF/p75 residues Lys401, Lys402, and Arg405 to glutamates (K401E/K402E/R405E, referred to as EEE) reduced WT HIV-Luc infection by approximately fivefold, yet boosted the activity of the weakly infectious reverse-charge KK (E10K/E13K) HIV-1 IN mutant virus by approximately sixfold (from ~2% with WT LEDGF/p75 to ~13% with EEE). 2014 Molecular therapy. Methods & clinical development Result HIV K401E;K402E;R405E;E10K;E13K;R405E 75;81;87;239;244;53 80;86;92;243;248;73 IN 256 258 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Although our biochemical analysis revealed a gain-of-function for RR IN from the K42E mutation in the presence of LEDGF/p75 EEE protein, the magnitude of the differential strand transfer activity effect appeared less than that observed during virus infection (compare Figures 5d and 4c). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 81 85 IN 69 71 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. By contrast, the RR and K42E IN mutations caused approximately three- to fivefold reverse transcription defects. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 24 28 RT;IN 82;29 103;31 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Combining the K42E and RR mutations interestingly restored IN mutant reverse transcription to ~70% of the level of WT HIV-Luc (Figure 6b). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 14 18 RT;IN 69;59 90;61 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Compared with the level of WT LEDGF/p75 protein bound by WT IN, K42E, RR, and RRE IN bound EEE LEDGF/p75 protein at ~42, 11, and 15% efficiency, respectively (Figure 5a, lanes 12-16, and Figure 5b). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 64 68 IN;IN 60;82 62;84 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. EEE LEDGF/p75 stimulated about 17% of WT IN concerted integration activity, though it failed to appreciably stimulate the K42E IN mutant protein (Figure 5c, lanes 10 and 11). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 122 126 IN;IN 41;127 43;129 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. From these data, we conclude that the K42E mutation is primarily if not solely responsible for the observed increase in replication fitness of the KR and RR IN mutant viruses in EEE-expressing cells. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 38 42 IN 157 159 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Infection of EEE LEDGF/p75-expressing cells by the RR HIV-Luc mutant virus was by contrast boosted approximately threefold by the K42E mutation, such that RRE attained 75% of the level of WT HIV-Luc infectivity on cells expressing WT LEDGF/p75 (Figure 4c). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 130 134 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. K42E, RR, and RRE INs supported about 83, 53, and 18% of the level of WT IN concerted integration activity in the presence of WT LEDGF/p75 (Figure 5c, lanes 6-9; quantified in Figure 5d). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 0 4 IN;IN 18;73 21;75 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Similar differential transduction levels were observed for each of the novel mutant viruses; as RR (E10R/E13R) and KR (E10K/E13R) would require six and four nucleotide changes, respectively, to revert to the WT sequence, they were earmarked for virus evolution. 2014 Molecular therapy. Methods & clinical development Result HIV E10K;E10R;E13R;E13R 119;100;105;124 123;104;109;128 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Stimulation of IN mutant viral DNA synthesis and integration by the K42E mutation. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 68 72 IN 15 17 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The K42E change moreover only marginally reduced WT LEDGF/p75-dependent IN strand transfer activity (Figure 5d), yet reduced HIV-Luc infectivity by ~10-fold (Figure 4c). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 4 8 IN 72 74 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The K42E mutation interestingly reduced HIV-Luc transduction of WT LEDGF/p75-expressing cells by ~10-fold, and in the absence of other IN changes did not confer any obvious preference for EEE or E4 LEDGF/p75. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 4 8 IN 135 137 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The K42E mutation reduced WT LEDGF/p75 binding by approximately twofold, whereas neither RR nor RRE IN bound a detectable level of WT LEDGF/p75 ( Figure 5a, lanes 1-11; quantified in Figure 5b). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 4 8 IN 100 102 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The KK mutant virus similarly transduced cells expressing EE (K402E/K405E), EEE, EELE, or QELE mutant LEDGF/p75 protein (Figure 1c). 2014 Molecular therapy. Methods & clinical development Result HIV K402E;K405E 62;68 67;73 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The most common pleiotropic defect among class II HIV-1 IN mutant viruses is reverse transcription, and K42E and RR were accordingly typed as class II IN mutant viruses. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 104 108 RT;IN;IN 77;56;151 98;58;153 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The results presented in Figure 4c show that the K42E mutation conferred gain-of-function to the RR mutant virus but not to WT HIV-1 under conditions that required integration and expression of the luciferase reporter gene. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 49 53 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The sequencing of overlapping PCR products that covered the entire genomes with the exception of the env gene in both cases revealed a single nucleotide A to G change at position 4353 in pol, which corresponded to the substitution of Glu for Lys42 (K42E) in the NTD of IN. 2014 Molecular therapy. Methods & clinical development Result HIV A4353G;K42E;K42E 153;249;234 183;253;247 Pol;Env;IN 187;101;269 190;104;271 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. To address if the electropositive Arg404 residue might interact intramolecularly with the electronegative mutant side chains in EEE (Figure 1a) and potentially interfere with mutant protein function, it was mutated to Leu in the context of EEE to yield EELE, or in the context of QEE (K401Q/K402E/R405E) to yield QELE. 2014 Molecular therapy. Methods & clinical development Result HIV K401Q;K402E;R405E 285;291;297 290;296;302 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. To address if the K42E gain-of-function phenotype was observed during the early stage of HIV-1 replication that includes integration, the mutation was introduced into WT and RR single-round constructs, and knockout MEFs expressing WT, EEE, or E4 (EEE with an added K360E change) LEDGF/p75 were infected with WT, RR, K42E, and RRE HIV-Luc. 2014 Molecular therapy. Methods & clinical development Result HIV K360E;K42E;K42E 265;18;316 270;22;320 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. To further investigate the molecular bases for the viral infection phenotypes, reverse transcription and integration were analyzed by quantitative PCR using single-round WT, RR, K42E, and RRE HIV-Luc viruses and TL3, WT, and EEE T cells. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 178 182 RT 79 100 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. To test the contribution of the K42E change to WT and RR IN protein function, the K42E, RR, and RRE mutations were engineered into a hexahistidine (His6)-tagged IN expression construct, and proteins purified following their expression in bacteria were tested in in vitro LEDGF/p75 binding and IN activity assays. 2014 Molecular therapy. Methods & clinical development Result HIV K42E;K42E 32;82 36;86 IN;IN;IN 57;161;293 59;163;295 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Two new molecular clones were made by introducing the K42E mutation into KR and RR HIV-1NL4-3, yielding KRE and RRE, respectively. 2014 Molecular therapy. Methods & clinical development Result HIV K42E 54 58 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. We note that the K42E mutation also boosted the infectivity of the RR mutant virus in the face of WT LEDGF/p75, from about 4% without the mutation to about 24% in its presence (Figure 4c). 2014 Molecular therapy. Methods & clinical development Result HIV K42E 17 21 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. 10b show interactions between NHR and these residues of N43D and N43D/S138A systems, respectively). 2014 PloS one Result HIV N43D;N43D;S138A 56;65;70 60;69;75 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. 3, wild type and N43D mutant have displayed different binding patterns. 2014 PloS one Result HIV N43D 17 21 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. 7, residues E137, S138, Q139, Q141 and Q142 show larger losses of van der Waals energy in N43D single mutant than wild type. 2014 PloS one Result HIV N43D 90 94 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. 7, the two curves for wild type and N43D mutant system are nearly superimoposable, except residues near the torsion. 2014 PloS one Result HIV N43D 36 40 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. after the mutation N43D on NHR of gp41, Q40, N/D43 and S138 showed larger losses of energetic contribution. 2014 PloS one Result HIV N43D 19 23 gp41 34 38 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. As displayed in Figure 4, CHR (C34) of N43D/S138A double mutant binds to NHR without structure torsion, CHR has inclined to NHR-B chain comparing with single mutant. 2014 PloS one Result HIV N43D;S138A 39;44 43;49 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. As shown in Table 1, it comes out that the contribution of molecular mechanics electrostatic energy (DeltaEele) is quite unfavorable for both N43D single mutant and N43D/S138A double mutant with values of 459.89 kcal/mol and 404.88 kcal/mol, and the electrostatic solvation terms (DeltaDeltaGPB), with values of -403.84 kcal/mol and -347.59 kcal/mol give compensation to the severe binding energy lost of DeltaEele. 2014 PloS one Result HIV N43D;N43D;S138A 142;165;170 146;169;175 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. At the N43D single mutant complex simulation, D43 made hydrogen bonding with Q141. 2014 PloS one Result HIV N43D 7 11 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. At this point we hypothesize that the compensatory mutation S138A (yielding N43D/S138A) would induce the greater hydrophobic interactions between NHR and CHR, enhance the binding of CHR and NHR, and in contrast to this, the binding affinity between the inhibitor and gp41 is reduced. 2014 PloS one Result HIV N43D;S138A;S138A 76;60;81 80;65;86 gp41 267 271 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. But in N43D mutant, only one hydrogen bond exists, which is formed between OD2 of D43 and Q141. 2014 PloS one Result HIV N43D 7 11 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. By this line of reasoning, the compensatory mutation S138A (yielding N43D/S138A) induced the greater hydrophobic interactions between NHR and CHR, and may led to greater resistance to drug than the single N43D escape mutant. 2014 PloS one Result HIV N43D;N43D;S138A;S138A 69;205;53;74 73;209;58;79 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Combining free energy data and hydrogen bonding, the N43D mutation seems to be an unfavorable mutation to binding. 2014 PloS one Result HIV N43D 53 57 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Compared with single mutant, the binding mode of N43D/S138A is much favorable for binding in this region, which leads to enhanced van der Waals interactions. 2014 PloS one Result HIV N43D;S138A 49;54 53;59 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Conversely, for double mutant, C34 forms stable interactions with NHR, because of the compensatory mutation S138A, ligand C34 moves into the other chain of NHR, and occupied the hydrophobic groove with different pattern of the wild type. 2014 PloS one Result HIV S138A 108 113 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Differently, van der Waals contribution (DeltaEvdW) has larger favorable contribution for N43D/S138A double mutant than single mutant. 2014 PloS one Result HIV N43D;S138A 90;95 94;100 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. For N43D mutant, the contribution from DeltaEele term is negative for binding with value of 459.89 kcal/mol, which is larger than that for wild type. 2014 PloS one Result HIV N43D 4 8 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. From Table 1, it comes out that the contribution from electrostatic component of molecular mechanics electrostatic energy (DeltaEele) strongly block the association of C34 with receptor, while the polar solvation term (DeltaDeltaGPB) shows favorable contribution to binding with complex N43D/S138A. 2014 PloS one Result HIV N43D;S138A 287;292 291;297 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. From Table 1, the contribution from electrostatic component of molecular-mechanical energy (DeltaEele) is characterized, in both two models, by relatively large positive values of DeltaEele, 169.67 kcal/mol (WT) and 459.89 kcal/mol (N43D mutant), with negative contributions to the binding free energies, DeltaEele significantly oppose complex formation. 2014 PloS one Result HIV N43D 233 238 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. From the analysis, it could be concluded that the electrostatic repulsion is the main reason that causes the van der Waals energy losses in N43D single mutant. 2014 PloS one Result HIV N43D 140 144 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. From the binding energy analysis, double mutant N43D/S138A shows more favorable binding energy than N43D single mutant, this could be due to changes as induced by the rearrangement of the binding poses of C34 during MD simulations. 2014 PloS one Result HIV N43D;N43D;S138A 48;100;53 52;104;58 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. However, in N43D mutant, structure torsion of inhibitor C34 would interfere with the orientation of these residues, the interaction involving these residues (residues after E137) and hydrophobic groove of NHR is changed, residues of C34 have more interactions with NHR-A. 2014 PloS one Result HIV N43D 12 16 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In fact, structure changes caused by electrostatic repulsion also have large unfavorable effects on hydrogen bonding interaction in N43D mutant. 2014 PloS one Result HIV N43D 132 136 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In fact, the energetic difference is related to the binding mode of ligand after the N43D mutation. 2014 PloS one Result HIV N43D 85 89 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In N43D mutant, these hydrogen bonds are collapsed, which may lead to enhanced mobility of inhibitor (C34) observed compare with wild type. 2014 PloS one Result HIV N43D 3 7 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In order to reveal differences of hydrogen bonding pattern between wild type and N43D mutant, we carried out comparative analyses of the hydrogen bonds (H-bonds) with an occupancy>30% over both complex trajectories (Table 2). 2014 PloS one Result HIV N43D 81 85 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In our simulation results, N43D/S138A double mutant displayed stronger binding energy than N43D, S138A mutation might compensate for the binding between NHR and CHR. 2014 PloS one Result HIV N43D;N43D;S138A;S138A 27;91;32;97 31;95;37;102 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In single mutant, N43D that induced the electrostatic repulsion led the interaction between NHR and C34 disrupted. 2014 PloS one Result HIV N43D 18 22 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. It indicated that compensatory mutation S138A may enhance the binding stabilization between NHR and CHR through additional hydrophobic contacts, as many studies mentioned. 2014 PloS one Result HIV S138A 40 45 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. It is evident from the structure that the inhibitor C34 behaves quite differently in the N43D single mutant versus how it behaves in the resistant double mutant, and its binding mode may be more stable in the double mutant model. 2014 PloS one Result HIV N43D 89 93 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. It is very important to note that the binding mode of N43D/S138A complex, which 1) alter the orientation of residues on the end of C34, thus allow the ligand embedded in the hydrophobic groove deeply, and stabilizes the inhibitor binding position in the complex through the increased van deer Waals interaction, 2) is involved in hydrogen bonding interactions with NHR. 2014 PloS one Result HIV N43D;S138A 54;59 58;64 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. It reveals that W117, W120, I124, Y127, T128, I131, L134, I135, A138, Q141 and Q142 of ligand in N43D/S138A double mutant make strong interactions with receptor. 2014 PloS one Result HIV N43D;S138A 97;102 101;107 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. It should be noted that N43D introduces a negative charge on gp41 leading to repulsion between receptor and ligand. 2014 PloS one Result HIV N43D 24 28 gp41 61 65 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. It should be noted that the main binding energy differences between N43D single mutant and N43D/S138A double mutant come from van der Waals contributions (DeltaEvdW). 2014 PloS one Result HIV N43D;N43D;S138A 68;91;96 72;95;101 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Moreover, DeltaEvdW is computed to be most favorable for the N43D/S138A double mutant (-125.40 kcal/mol) compared with the systems. 2014 PloS one Result HIV N43D;S138A 61;66 65;71 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Mutation on CHR, like S138A associated with the appearance of NHR N43D mutation, could restore fusion rates and show increased level resistance over than single mutant. 2014 PloS one Result HIV N43D;S138A 66;22 70;27 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. N43D single mutant and N43D/S138A mutant. 2014 PloS one Result HIV N43D;S138A;N43D 23;28;0 27;33;4 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. N43D single mutation. 2014 PloS one Result HIV N43D 0 4 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. N43D/S138A double mutant. 2014 PloS one Result HIV S138A;N43D 5;0 10;4 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. N43D/S138A double mutation. 2014 PloS one Result HIV S138A;N43D 5;0 10;4 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. On the other hand, the dominant different between WT and N43D is DeltaEvdW term. 2014 PloS one Result HIV N43D 57 61 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Overall, the energy analysis suggests that inhibitory activity of ligand C34 mimics for wild type and the C34 with S138A mutation is primarily controlled by, and best described by, van der Waals contributions (DeltaEvdW), and the negative value for DeltaDeltaGnp+ DeltaEvdW, which can be thought of as the intermolecular hydrophobic effect, is generally larger in magnitude than DeltaDeltaGPB. 2014 PloS one Result HIV S138A 115 120 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Per-residue changes in DeltaEelec term were computed both in wild type and N43D mutant models. 2014 PloS one Result HIV N43D 75 79 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. S138A mutation might play a compensate role that rescue the binding between NHR and CHR. 2014 PloS one Result HIV S138A 0 5 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Similar to that observed from N43D mutant and WT system, DeltaEvdW plays the dominant contribution for N43D/S138A double mutant in the binding modes between ligand and gp41. 2014 PloS one Result HIV N43D;N43D;S138A 30;103;108 34;107;113 gp41 168 172 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Since the structure torsion changes the binding mode of residues 137-145 to receptor, the reduced interaction of this region of N43D mutation may interfere with the stability of binding, alterated of stability on this region mainly manifests in the higher RMS fluctuations. 2014 PloS one Result HIV N43D 128 132 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Summing up the H-bonds at interface, we can see seven residues N43, S138, E49, Q139, Q40, Q141 and Q142 are involved in H-bonding in wild model, and for N43D mutation complex, only Q141 and mutation N43D are involved in hydrogen bond formation. 2014 PloS one Result HIV N43D;N43D 153;199 157;203 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The absolute values of the van der Waals contributions (DeltaEvdW) are -121.74 kcal/mol for wild type and -111.88 for N43D mutant, giving dominant contributions to the final binding free energies. 2014 PloS one Result HIV N43D 118 122 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The binding region in N43D mutant is similar to that found in WT, while the configuration of inhibitor C34 is different, in the N43D mutant, the single mutation would cause the structure torsion of C34. 2014 PloS one Result HIV N43D;N43D 22;128 26;132 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The calculated values of total binding free energy for formation of N43D/S138A double mutant (-83.57 kcal/mol) is more favorable than N43D single mutant (-70.12 kcal/mol). 2014 PloS one Result HIV N43D;N43D;S138A 68;134;73 72;138;78 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The mutation N43D affects the conformation of the residues from 137 to 145 on inhibitor C34 far away from the hydrophobic grooves, and the electrostatic repulsion would affect the binding stability of inhibitor, thus might reduce the efficiency of inhibitor. 2014 PloS one Result HIV N43D 13 17 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The mutation S138A could explain the differential behavior of the inhibitor C34 in two systems. 2014 PloS one Result HIV S138A 13 18 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The negative value for DeltaDeltaGPB is generally large in magnitude, which could partially compensate the energy losses of DeltaEele, so the total electrostatic energy of N43D/S138A double mutant system is similar to N43D single mutant. 2014 PloS one Result HIV N43D;N43D;S138A 172;218;177 176;222;182 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The nonpolar component of solvation energy (DeltaDeltaGnp) are characterized by relatively large negative values of DeltaDeltaGPB, -14.62 kcal/mol for wild type and -14.3 kcal/mol for N43D mutant, which have positive contributions to binding. 2014 PloS one Result HIV N43D 184 188 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The presence of the N43D mutation on NHR could affect the binding between inhibitor C34 and NHR. 2014 PloS one Result HIV N43D 20 24 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The structure of these two models display different binding patterns, compare with WT system, in the mutation type, this domain of the ligand bind with receptor in a stance of torsion indicating that N43D mutation would affect the binding. 2014 PloS one Result HIV N43D 200 204 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Therefore, the total electrostatic energy contribution (PBELE = DeltaEelec+DeltaDeltaGPB) to N43D/S138A double mutant (57.30 kcal/mol) is comparable with values of N43D single mutant (56.05 kcal/mol). 2014 PloS one Result HIV N43D;N43D;S138A 93;164;98 97;168;103 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. This binding mode of double mutant seems to be an acceptable model that eliminates the fitness defect of HIV-1 that caused by N43D mutation on NHR. 2014 PloS one Result HIV N43D 126 130 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. This defect observed in N43D single mutation may obstruct the stability of 6-HB conformation, thereby may disturb the membrane fusion and the fusion rates. 2014 PloS one Result HIV N43D 24 28 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. To track the extent of variation of individual residues of inhibitor C34 in complex, the per-residue root-mean-square fluctuations (RMSFs) of backbone atoms were computed, over the 15 ns MD simulation of inhibitor C34 in N43D mutation, we observed the 137-150 peptide of the N43D mutation type shows higher RMS fluctuations than that found in WT system. 2014 PloS one Result HIV N43D;N43D 221;275 225;279 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Upon examination, we found that this is mainly owing to the charged mutation N43D, in the wild type (WT) residues in this region would interact with Asn43 of HR1 and form the Hydrogen bonds, but in the mutant type (N43D), interactions are found to be unconspicuous, the substitution of Asp for Asn breaks these interactions. 2014 PloS one Result HIV N43D;N43D 77;215 81;219 Asp 286 289 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. we can observe that in two systems (the wild type and N43D mutant), residues Q40, N/D43 and S138 have large differences for energetic contribution. 2014 PloS one Result HIV N43D 54 58 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. We examined the contact residues of E137, S138A, Q139, Q141 and Q142 for two systems with cutoff of 8.5 A. 2014 PloS one Result HIV S138A 42 47 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. We examined the structure of N43D single mutant system and found that S138 could contact with L45 and D43. 2014 PloS one Result HIV N43D 29 33 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. When mutation N43D prevents the binding of inhibitor, it would have impact on the binding of the CHR domain as well, and lead to dramatic changes in the NHR-CHR interface. 2014 PloS one Result HIV N43D 14 18 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. When the N43 and S138 residues are mutated to aspartic and alanine, the S138A mutation might affect the conformation of CHR near the hydrophobic grooves that adopts a more constrained conformation with the residues before S133 pointing in the opposite direction of the NHR. 2014 PloS one Result HIV S138A 72 77 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Wild-type and N43D mutant. 2014 PloS one Result HIV N43D 14 18 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Wild-type and N43D single mutant. 2014 PloS one Result HIV N43D 14 18 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. A G248E mutation was also detected at the same time when the T242N mutation occurred in CH58. 2014 Retrovirology Result HIV G248E;T242N 2;61 7;66 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. All three T242N mutants replicated as well as their corresponding T/F viruses when the T/F and T242N mutant viruses were cultured independently (Figure 1d-f). 2014 Retrovirology Result HIV T242N;T242N 10;95 15;100 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Both CH58NV and CH470NV replicated similarly to their T/F viruses and T242N mutants (Figure 1d and e). 2014 Retrovirology Result HIV T242N 70 75 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. CH131 was infected with a T242N escape mutant and did not have the HLA-B*57/5801 alleles. 2014 Retrovirology Result HIV T242N 26 31 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Examination of the cyclophilin A (CypA) binding loop sequences showed that the glutamine at position 219, which can compensate fitness costs due to the T242N mutation, was present only in the CH40 T/F virus. 2014 Retrovirology Result HIV T242N 152 157 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Examination of the TW10 epitope sequences in these three viruses showed that they all had Isoleucine (Ile) at position 247 (Figure 1a-c), which could compensate the fitness loss caused by the T242N mutation in CH77 but neither I247 nor V247 alone had detectable fitness impact on the cognate T/F virus. 2014 Retrovirology Result HIV I247I;T242N 87;192 125;197 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, it became undetectable while the T242N mutation was fixed in the viral population at day 350. 2014 Retrovirology Result HIV T242N 42 47 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, no VL decrease was observed in CH77 and CH58 after the T242N escape mutation was fixed in the viral population (Figure 4). 2014 Retrovirology Result HIV T242N 64 69 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, the fitness impact of the T242N mutation has not been determined in the cognate transmitted T242N escape mutant. 2014 Retrovirology Result HIV T242N;T242N 35;101 40;106 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, the fitness losses caused by the T242N mutation were different among these three T242N mutants. 2014 Retrovirology Result HIV T242N;T242N 42;90 47;95 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, the T242N escape mutant viruses were frequently transmitted into new hosts and its reversion back to the wild type generally took months or years. 2014 Retrovirology Result HIV T242N 13 18 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. However, VL did not decreased in CH58 either, although the T242N escape mutant was significantly less fit than the T/F virus (Figure 4). 2014 Retrovirology Result HIV T242N 59 64 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. In all three comparisons, the T242N mutants were outgrown by the corresponding T/F viruses over time in the culture (Figure 2a-c). 2014 Retrovirology Result HIV T242N 30 35 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Interestingly, the T242N mutation is almost exclusively (95%) found linked to Q219 and/or I247 in the database (Figure 5). 2014 Retrovirology Result HIV T242N 19 24 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. It subsequently served as a compensatory mutation to significantly restore the fitness loss caused by the T242N mutation that was selected by later T cell responses. 2014 Retrovirology Result HIV T242N 106 111 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Our previous study showed that the T242N mutation resulted in a significantly reduced T cell response while the G248E mutation only modestly affected T cell responses. 2014 Retrovirology Result HIV G248E;T242N 112;35 117;40 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Since the G248E was not clearly associated with T cell escape, it existed only transiently in the viral population, and the focus of the currently study was to determine fitness costs of the T242N mutation in different genetic backgrounds, the G248E mutation was not further studied. 2014 Retrovirology Result HIV G248E;G248E;T242N 10;244;191 15;249;196 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Since the reversion of the T242N to the wild type did not have any impact on the fitness of the escape mutant, the reversion of the T242N escape mutation would take a long time to occur in CH131 and as reported in other studies. 2014 Retrovirology Result HIV T242N;T242N 27;132 32;137 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Taken together, our data demonstrated that the fitness costs caused by the T242N mutation could be significantly mitigated by preexisting compensatory amino acids. 2014 Retrovirology Result HIV T242N 75 80 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The CTL escape mutation T242N caused various levels of fitness loss in different virus backbones. 2014 Retrovirology Result HIV T242N 24 29 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The fitness loss due to the T242N mutation could be compromised by the preexisting compensatory amino acids. 2014 Retrovirology Result HIV T242N 28 33 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The fixation of fitness-impairing T242N mutation did not lead to the viral load decrease. 2014 Retrovirology Result HIV T242N 34 39 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The G248E mutation, however, abrogated binding of KIR3DL1 to HLA-B*5703, suggesting the emergence of this mutation was more likely associated with NK cell recognition. 2014 Retrovirology Result HIV G248E 4 9 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The reversion of the T242N mutation was first detected at day 273 and was fixed at day 670 (Figure 3a). 2014 Retrovirology Result HIV T242N 21 26 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The slow fixation of the reversion mutation T242N in the viral population in CH131 (397 days between the first detection and the fixation) (Figure 4) and other viruses lends further support to the view that the fitness cost of the T242N mutation was well compensated. 2014 Retrovirology Result HIV T242N;T242N 44;231 49;236 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The T242N mutation is present in 13% of viruses in the Los Alamos HIV sequence database (Figure 5), suggesting that the T242N CTL escape mutant is frequently transmitted and does not revert back quickly. 2014 Retrovirology Result HIV T242N;T242N 4;120 9;125 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The T242N mutation was first detected 45 days post screening and was fixed in the viral population at day 350 in patient CH58 who was positive for HLA-B*57, which presents TW10 (Figure 1a), while it was not selected in CH470 and CH40 (Figure 1b and c), neither of which carry HLA-B*57/5801 alleles. 2014 Retrovirology Result HIV T242N 4 9 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The transmitted CTL escape mutants carrying the T242N mutation were thought to be less fit than the wild type viruses. 2014 Retrovirology Result HIV T242N 48 53 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The transmitted CTL escape T242N mutant had no significant fitness costs. 2014 Retrovirology Result HIV T242N 27 32 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The V247I mutation was selected by T cell responses before the T242N T cell escape mutation in CH77 which had Val at position 247. 2014 Retrovirology Result HIV T242N;V247I 63;4 68;9 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Therefore, we introduced the Q219H mutation into CH40T242N to generate double mutant CH40HN, which also replicated as well as its T/F virus and T242N mutant (Figure 1f). 2014 Retrovirology Result HIV Q219H;T242N 29;144 34;149 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. These observations suggested that the T242N mutants might not be less fit than the wild type viruses. 2014 Retrovirology Result HIV T242N 38 43 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. These results demonstrated that the impaired fitness of the transmitted T242N escape mutant was fully repaired by the compensatory amino acid I247. 2014 Retrovirology Result HIV T242N 72 77 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. These results demonstrated that the T cell escape mutation T242N could decrease the viral fitness in different T/F viruses but the levels of fitness loss varied in the different virus backbones. 2014 Retrovirology Result HIV T242N 59 64 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. These results showed that the T242N mutants without the compensatory amino acids were significantly less fit than the corresponding T/F viruses and the T242N mutants with the compensatory amino acids. 2014 Retrovirology Result HIV T242N;T242N 30;152 35;157 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. This pervasive lack of association between the fixation of the T242N mutation and the VL decrease suggested that the significant fitness costs were generally compensated during fixation. 2014 Retrovirology Result HIV T242N 63 68 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Thus, the clinical benefits of the T242N escape mutation could be mitigated significantly since the predominance of the compensatory amino acid can readily counteract the fitness loss of the T242N escape mutants in those individuals, as shown in a recent study in which the high population-level frequency of compensatory mutations for T cell escape mutation in TW10 and KF9 epitopes were found associated with limited protective effect of the B*5801 allele. 2014 Retrovirology Result HIV T242N;T242N 35;191 40;196 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Thus, the significant fitness cost of the T242N mutation could have caused a significant viral load (VL) decrease if it was fixed in the viral population. 2014 Retrovirology Result HIV T242N 42 47 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. To determine if the compensatory amino acids alone could cause fitness loss and contributed to the increased fitness loss in the NV or NH double mutants, we generated T/F mutants that contained the compensatory amino acids but not the T242N mutation (the I247V mutation in CH58 and CH470 as well as the Q219H in CH40; Figure 1d-f). 2014 Retrovirology Result HIV I247V;Q219H;T242N 255;303;235 260;308;240 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. To determine if the preexisting I247 also mitigated the T242N mutation's impact in these T/F viruses, we removed this potential compensatory amino acid by introducing the I247V mutation into each T242N mutant to generate double mutant viruses (NV). 2014 Retrovirology Result HIV I247V;T242N;T242N 171;56;196 176;61;201 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. To determine whether the T242N mutation could cause similar fitness loss in different viral backbones, we introduced it into these three T/F genomes. 2014 Retrovirology Result HIV T242N 25 30 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. To determine whether the T242N reversion mutation (N242T) could render the transmitted T242N escape mutant more fit, we generated the N242T reversion mutant by substituting N242 with T242 in the CH131 T/F viral genome and compared its fitness with the CH131 T/F virus. 2014 Retrovirology Result HIV N242T;N242T;T242N;T242N 51;134;25;87 56;139;30;92 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. To test whether the absence of detectable fitness costs of the T242N mutation in the T/F virus was due to the presence of compensatory I247, we generated the CH131I247V mutant by introducing the I247V mutation in the T/F viral genome (Figure 3b). 2014 Retrovirology Result HIV I247V;T242N 195;63 200;68 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Using the mathematical model that we developed earlier, we found that all three T242N mutants were significantly less fit than their corresponding T/F viruses (p = 0.04 for CH58T242N and CH40T242N; p = 0.007 for CH470T242N). 2014 Retrovirology Result HIV T242N 80 85 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. We then determined their relative fitness by growing both the T242N mutant and its corresponding T/F virus in the same culture and determining the proportion of each virus over time using the parallel allele-specific sequencing (PASS) method, in which two compared viruses (wild type and mutant) were grown in the same cell culture, and proportions of the viruses at different time points were determined by directly detecting the wild type and mutant bases in the viral genomes through analysis of a large number of viruses in the culture supernatant. 2014 Retrovirology Result HIV T242N 62 67 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. As expected (Figure 3) with the high concentration of BI-D (~5 mM) used in the crystallographic experiments, the inhibitor bound to H171T CCD dimers. 2014 Retrovirology Result HIV H171T 132 137 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. As indicated in Figure 1A and B, the H171T IN substitution did not significantly alter virus release from transfected cells as measured by p24 production or affect the infectivity of the mutant virus. 2014 Retrovirology Result HIV H171T 37 42 p24;IN 139;43 142;45 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. BI-D binding to H171T IN CCD resulted in a significantly higher Kd of 10.3 muM. 2014 Retrovirology Result HIV H171T 16 21 IN 22 24 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Experimentally, the Kd of LEDGF/p75 binding to wild type and H171T mutant INs are ~3.3 nM and 10.5 nM respectively. 2014 Retrovirology Result HIV H171T 61 66 IN 74 77 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. For comparison, BI-D, which unlike LEDGIN-6 contains the tert-butoxy group, was significantly more sensitive (~68-fold, Table 1) to the H171T IN substitution in HIV-1NL4.3 likely due to the disruption of the hydrogen bonding between the tert-butoxy ether oxygen and Ndelta-protonated His171. 2014 Retrovirology Result HIV H171T 136 141 IN 142 144 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. For comparison, Table 2 also shows the DeltaGbind (exp) values determined using experimental Kd values for BI-D binding to WT and H171T IN CCDs (Figure 3). 2014 Retrovirology Result HIV H171T 130 135 IN 136 138 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. For inhibitor experiments, we examined two concentrations of BI-D: one (~0.120 muM) that correlated to the Kd value of the inhibitor binding to WT IN CCD (~0.123 muM) and the other (10 muM) that correlated with the Kd value for inhibitor binding to H171T IN CCD (~10.3 muM). 2014 Retrovirology Result HIV H171T 249 254 IN;IN 147;255 149;257 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Free energy perturbation analysis allowed us to calculate that DeltaDeltaGb = DeltaGb(H171T) - DeltaGb(WT) = 1.08 kcal/mol. 2014 Retrovirology Result HIV H171T 86 91 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Furthermore, the H171T substitution did not detectably affect the inhibitor position within the binding pocket (compare Figure 5A and B). 2014 Retrovirology Result HIV H171T 17 22 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. However, at the same concentration of BI-D the H171T IN mutant virus resulted in only 27% of the virions with eccentric core morphologies (Figure 2). 2014 Retrovirology Result HIV H171T 47 52 IN 53 55 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. However, the H171T IN substitution resulted in significantly higher levels of resistance (~68-fold) when drug exposure was limited to the late stage of replication. 2014 Retrovirology Result HIV H171T 13 18 IN 19 21 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. However, under conditions of increased inhibitor, BI-D is able to bind H171T IN (Figure 3) and promote aberrant IN multimerization (Figure 4D). 2014 Retrovirology Result HIV H171T 71 76 IN;IN 77;112 79;114 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. However, when the concentration of BI-D was increased to 10 muM, higher order oligomerization of H171T IN was detected in a time dependent manner (Figure 4D). 2014 Retrovirology Result HIV H171T 97 102 IN 103 105 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. In contrast, the same BI-D concentration (0.12 muM) failed to elicit higher order H171T IN oligomers even after 30 min incubation (Figure 4B). 2014 Retrovirology Result HIV H171T 82 87 IN 88 90 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. LEDGIN-6 was only ~3.4-fold less potent with respect to HIV-1NL4.3 (H171T IN) (EC50 of 41.4 +- 6.4 muM) (data not shown) versus WT HIV-1NL4.3 (EC50 of 12.2 +- 2.9 muM). 2014 Retrovirology Result HIV H171T 68 74 IN 74 76 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Next, we wanted to understand the structural basis as to why the H171T substitution had significantly less effect on LEDGF/p75 binding (~3.2-fold) compared with BI-D binding (~84-fold) to recombinant HIV-1 IN. 2014 Retrovirology Result HIV H171T 65 70 IN 206 208 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Significantly, the observed ~84-fold decrease in the binding affinity of BI-D to the mutant IN CCD (Figure 3) roughly correlated with the ~68-fold decrease in the EC50 value seen for antiviral activity against HIV-1NL4-3 bearing the H171T IN substitution (Table 1). 2014 Retrovirology Result HIV H171T 233 238 IN;IN 92;239 94;241 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Size exclusion chromatography (SEC) experiments revealed that WT and H171T INs similarly formed tetramers and monomers (Figure 1C). 2014 Retrovirology Result HIV H171T 69 74 IN 75 78 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Surface plasmon resonance (SPR) was used to compare BI-D binding to recombinant WT and H171T IN CCD proteins. 2014 Retrovirology Result HIV H171T 87 92 IN 93 95 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The virus containing the H171T IN substitution still conferred resistance to BI-D in the absence of endogenous LEDGF/p75, with 28- and 45-fold resistance observed in the KO cells during the early and late stages, respectively. 2014 Retrovirology Result HIV H171T 25 30 IN 31 33 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Therefore, we compared the effects of BI-D on aberrant multimerization of WT and H171T INs using dynamic light scattering (DLS). 2014 Retrovirology Result HIV H171T 81 86 IN 87 90 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. This indicates that the H171T IN substitution confers resistance to BI-D by decreasing inhibitor binding affinity and hence correspondingly decreasing aberrant IN multimerization. 2014 Retrovirology Result HIV H171T 24 29 IN;IN 30;160 32;162 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. This suggested that even though the H171T IN substitution is within the IN-LEDGF/p75 binding pocket, IN retains the ability to effectively bind LEDGF/p75 in vitro and during virus infection. 2014 Retrovirology Result HIV H171T 36 41 IN;IN;IN 42;72;101 44;74;103 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. This suggests that at lower concentrations, BI-D is unable to promote higher order IN oligomerization of H171T IN likely due to the decreased affinity of the inhibitor binding to the mutant protein (Figure 3). 2014 Retrovirology Result HIV H171T 105 110 IN;IN 83;111 85;113 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To assess the functional significance of the H171T IN substitution we introduced the mutation into both HIV-1NL4.3 and recombinant IN. 2014 Retrovirology Result HIV H171T 45 50 IN;IN 51;131 53;133 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To examine LEDGF/IBD interactions with the mutant IN we simulated the H171T change in the available crystal structure, which revealed that unlike BI-D, LEDGF/IBD made the same number of hydrogen bonds with WT and H171T mutant INs (Additional file 1: Figure S3). 2014 Retrovirology Result HIV H171T;H171T 70;213 75;218 IN;IN 50;226 52;229 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To further test these observations, we performed relative binding free energy calculations for LEDGF/IBD binding to WT and H171T IN CCDs. 2014 Retrovirology Result HIV H171T 123 128 IN 129 131 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To further test this notion we have examined the effects of the H171T IN substitution on the antiviral activities of LEDGIN-6, which lacks the tert-butoxy group (, also see Additional file 1: Figure S1). 2014 Retrovirology Result HIV H171T 64 69 IN 70 72 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To gain insight into the mechanism of BI-D action and the mode of H171T resistance, HIV-1NL4-3(H171T IN) was evaluated during both the early and late stages of the replication lifecycle. 2014 Retrovirology Result HIV H171T;H171T 66;95 71;100 IN 101 103 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To test this directly, we compared LEDGF/p75 binding to WT and H171T INs utilizing a HTRF-based binding assay. 2014 Retrovirology Result HIV H171T 63 68 IN 69 72 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To understand how these structural differences contributed to the markedly reduced ability of the inhibitor to bind H171T IN, we performed absolute binding free energy calculations for the interactions between WT and H171T IN CCD dimers with BI-D (Table 2 and Additional file 1: Figure S2). 2014 Retrovirology Result HIV H171T;H171T 116;217 121;222 IN;IN 122;223 124;225 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. To understand the structural basis for the reduced binding affinity of BI-D to H171T IN, we solved the crystal structure of BI-D in complex with H171T CCD dimer (Figure 5A) and compared it to the complex of inhibitor bound to WT CCD dimer (, also see Figure 5B). 2014 Retrovirology Result HIV H171T;H171T 79;145 84;150 IN 85 87 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. We compared the results for both BI-D binding to the H171T IN CCD and its WT counterpart (data not shown), which suggests that the less favorable electrostatic interactions between BI-D and Thr171 primarily contribute to the lower Kd value for the inhibitor binding to the mutant protein. 2014 Retrovirology Result HIV H171T 53 58 IN 59 61 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. We next examined the biochemical properties of purified recombinant H171T IN. 2014 Retrovirology Result HIV H171T 68 73 IN 74 76 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. We next wished to dissect the mechanism of the HIV-1NL4-3(H171T IN) resistance to BI-D. 2014 Retrovirology Result HIV H171T 58 63 IN 64 66 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. When BI-D concentrations were increased to 12 muM, which corresponds to 2xEC50 for HIV-1NL4-3 bearing the H171T IN substitution, the eccentric virion morphology for the mutant virus increased to 82% (Figure 2). 2014 Retrovirology Result HIV H171T 106 111 IN 112 114 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. When drug exposure was limited to the acute phase of infection, BI-D EC50 values increased from 1.17 muM for VSV-G pseudotyped HIV-1NL4-3 to 12.4 muM for the VSV-G pseudotyped HIV-1NL4-3(H171T IN), ~11-fold resistance (Table 1). 2014 Retrovirology Result HIV H171T 187 192 IN 193 195 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. WT IN bound LEDGF/p75 with a Kd of 3.3 +- 0.3 nM, whereas H171T IN bound LEDGF/p75 with a Kd of ~10.5 +- 0.3 nM, a 3.2-fold decrease in affinity (Figure 1F). 2014 Retrovirology Result HIV H171T 58 63 IN;IN 3;64 5;66 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. After 10 days of selection, we counted a higher number of clones for WT and D167H vectors than that for NILV (P < 0.001; Figure 4a,b). 2014 Molecular therapy. Nucleic acids Result HIV D167H 76 81 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Altogether, these results indicate that the effect of the D167H substitution in improving transduction efficiency is not restricted to HEK-293T cells. 2014 Molecular therapy. Nucleic acids Result HIV D167H 58 63 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Among the four NILV, transduction efficiency with D64V was two to six times higher than that observed with other mutants. 2014 Molecular therapy. Nucleic acids Result HIV D64V 50 54 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. At 72 hours after transduction, integrated copies of D167H vectors were about 1.7 times higher than that of WT vectors. 2014 Molecular therapy. Nucleic acids Result HIV D167H 53 58 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. At multiplicity of infection (MOI) 50 or 100 vRNAc, integration of D64V vectors mainly occurred between 0 and 48 hours after transduction then seemingly reaching a plateau. 2014 Molecular therapy. Nucleic acids Result HIV D64V 67 71 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. At the higher dose of 100 vRNAc/cell, WT and D167H vectors transduced 100% of the cells (Figure 3b), but D167H vector permitted a 1.5 times higher MFI (Figure 3d). 2014 Molecular therapy. Nucleic acids Result HIV D167H;D167H 45;105 50;110 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Cells transduced with higher input of D167H vector (300 and 900 vRNAc/cell) also displayed an equivalent increased MFI as compared with WT vector, indicating a nonsaturating gain of function (Supplementary Figure S2b). 2014 Molecular therapy. Nucleic acids Result HIV D167H 38 43 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Here, we also observed that IN mutations impairing integration produced an increased number of LTR deletions (Q168A, 1.8%; LQ, 16.8%; D64V, 21.6%; N, 44.7%), while D167H and WT IN displayed the same low frequency of deletion (0.3%; Supplementary Table S2). 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V;Q168A 164;134;110 169;138;115 LTR;IN;IN 95;28;177 98;30;179 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Here, we observed that the reduced frequency of integration within gene-dense regions was variable among NILVs as compared to WT and D167H (70% of integration in gene coding regions); it was moderate for Q168A (~65%), but more prominent for the N mutant (~45%), as compared with D64V and LQ (~50%). 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V;Q168A 133;279;204 138;283;209 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. IN D64V + D167H allows more integration events than IN D64V. 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V;D64V 10;55;3 15;59;7 IN;IN 0;52 2;54 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. In these conditions, we also observed that the D167H mutant produced about 1.5 times more colonies than a vector with WT IN (P < 0.001; Figure 4a). 2014 Molecular therapy. Nucleic acids Result HIV D167H 47 52 IN 121 123 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Integration of D64V+D167H, instead, kept increasing linearly until the last time point analyzed at 72 hours after transduction (Figure 6a,b). 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V 20;15 25;19 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Interestingly, these forms of HIV vector genomes were decreased for D167H vectors as compared with WT at 72 hours after transduction (Figure 6e). 2014 Molecular therapy. Nucleic acids Result HIV D167H 68 73 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. It was chosen to alter D167-K360 interaction between IN and LEDGF/p75 (ref.) and compare its effects on vector transduction to that of mutant Q168A. 2014 Molecular therapy. Nucleic acids Result HIV Q168A 142 147 IN 53 55 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Kinetics of integration of vectors carrying the D167H mutation. 2014 Molecular therapy. Nucleic acids Result HIV D167H 48 53 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. LV with D167H substitution improves CD34+ cell transduction. 2014 Molecular therapy. Nucleic acids Result HIV D167H 8 13 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Mutant Q168A had an intermediary phenotype and was about 15 times less integrative than WT and 10 to 50 times more integrative than mutants LQ and N or D64V (P < 0.001). 2014 Molecular therapy. Nucleic acids Result HIV D64V;Q168A 152;7 156;12 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Mutant Q168A was the second most efficient, followed by N and LQ (Supplementary Figure S2a). 2014 Molecular therapy. Nucleic acids Result HIV Q168A 7 12 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Mutations D64V, N, LQ, and Q168A affect HIV integration but have never been directly compared. 2014 Molecular therapy. Nucleic acids Result HIV D64V;Q168A 10;27 14;32 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Of the four nonintegrating vectors, the one carrying the D64V mutation displays the best transduction efficiency. 2014 Molecular therapy. Nucleic acids Result HIV D64V 57 61 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Particles carrying the D167H IN allowed about two times higher transduction of CD34+ cells compared with WT particles (Figure 7). 2014 Molecular therapy. Nucleic acids Result HIV D167H 23 28 IN 29 31 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Previous analysis of integration patterns of lentiviral vectors showed that genomes integrated by a D64V IN suffer about 10 times more deletions within LTRs than that of vector genomes integrated by a WT IN. 2014 Molecular therapy. Nucleic acids Result HIV D64V 100 104 LTR;IN;IN 152;105;204 156;107;206 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Previous studies showed that HIV and derived vectors integrate preferentially within transcribed genes (70%), while this trend is reduced in cells depleted in LEDGF or TNPO3 (refs.) and for vectors carrying a mutant D64V IN. 2014 Molecular therapy. Nucleic acids Result HIV D64V 216 220 IN 221 223 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Primary human cord blood CD34+ cells were incubated with equal vRNAc of D167H and WT vectors. 2014 Molecular therapy. Nucleic acids Result HIV D167H 72 77 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Supplementary Table S4, summarizing the 10 highest CIS orders for individual vector types, shows that the mean of the highest order of CIS is 11.4 for vectors with WT IN but is 1.6 times higher for vectors D167H (18.6) and 2 to 6 times lower for vectors Q168A and other NILVs (Supplementary Table S4). 2014 Molecular therapy. Nucleic acids Result HIV D167H;Q168A 206;254 211;259 IN 167 169 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Surprisingly, across several experiments using different stocks of vectors, we observed that D167H vector allowed a 1.5 times higher transduction efficiency than WT vector, a significant increase noted at all time points of analysis (Figure 3a). 2014 Molecular therapy. Nucleic acids Result HIV D167H 93 98 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Surprisingly, when we measured integration, by selecting puromycin-resistant clones starting at day 4 after transduction, we observed that the double mutant D64V+Q167H led to a significant increase of clones (1.5 times more) as compared with the mutant D64V (Figure 5c). 2014 Molecular therapy. Nucleic acids Result HIV D64V;D64V;Q167H 157;253;162 161;257;167 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The amount of vRNAc/ml tended to be reduced in vectors Q168A, N, and LQ as compared with WT, D167H, or D64V, but this difference was not statistically significant (Supplementary Figure S1b). 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V;Q168A 93;103;55 98;107;60 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The D64V mutant was the least integrative giving about 700 times less colonies than WT and about 5 times less colonies than N and LQ mutants (P < 0.001). 2014 Molecular therapy. Nucleic acids Result HIV D64V 4 8 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The former tended to integrate between 0 and 48 hours after transduction, as reported before, while the mutant D167H kept integrating between 48 and 72 hours after transduction (Figure 6c). 2014 Molecular therapy. Nucleic acids Result HIV D167H 111 116 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The four mutants (D64V, Q168A, N, and LQ) displayed a nonintegrating phenotype (NILV) with GFP clearance over time (Supplementary Figure S2a). 2014 Molecular therapy. Nucleic acids Result HIV D64V;Q168A 18;24 22;29 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The highest CIS order observed is CIS of the 27th order in the D167H data set to occur on chromosome 8. 2014 Molecular therapy. Nucleic acids Result HIV D167H 63 68 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The kinetics of integration of WT and D167H vectors were also different. 2014 Molecular therapy. Nucleic acids Result HIV D167H 38 43 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The lower frequency of IS in cells transduced with NILVs was most prominent for D64V, N, and LQ in comparison to data obtained with Q168A vector, which is in line with the higher number of clones obtained after transducing HEK-293T cells with this vector (Figure 4 and Supplementary Figure S3). 2014 Molecular therapy. Nucleic acids Result HIV D64V;Q168A 80;132 84;137 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The nonconservative D167H substitution is studied for the first time. 2014 Molecular therapy. Nucleic acids Result HIV D167H 20 25 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Then, although TU/ml was higher for vector with D167H IN as compared with all other vectors, this difference was not significant (Supplementary Figure S1c). 2014 Molecular therapy. Nucleic acids Result HIV D167H 48 53 IN 54 56 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. These data also indicate that after normalization of TU/ml with vRNAc/ml, D167H mutant vectors present a significant advantage for cell transduction over the other vectors including WT. 2014 Molecular therapy. Nucleic acids Result HIV D167H 74 79 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. These results indicate that IN D167H substitution lengthens the kinetics of integration of HIV vectors. 2014 Molecular therapy. Nucleic acids Result HIV D167H 31 36 IN 28 30 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. This indicates that a significant proportion of D167H linear vectors still integrated at later time points, while during this same period, WT linear vectors were lost. 2014 Molecular therapy. Nucleic acids Result HIV D167H 48 53 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. This indicates that the overall integration rate of the vector D167H is higher than that of WT, as at equivalent MOI of either vectors (100 vRNAc), D167H leads to an increased copy number within single cell CIS. 2014 Molecular therapy. Nucleic acids Result HIV D167H;D167H 63;148 68;153 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. This suggests that the D167H mutation introduces a change in a NILV vector toward a form more prone to integration. 2014 Molecular therapy. Nucleic acids Result HIV D167H 23 28 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. This trend was further confirmed with real-time Alu-LTR PCR, which showed that integrated copies of WT vectors remained equivalent at 48 and 72 hours while they kept increasing for vector D167H (Figure 6f). 2014 Molecular therapy. Nucleic acids Result HIV D167H 188 193 LTR 52 55 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Thus, D167H mutant vector has an integrating phenotype and appears improved for transducing HEK-293T cells compared with WT. 2014 Molecular therapy. Nucleic acids Result HIV D167H 6 11 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Thus, of all the vectors compared here, the one containing the D167H mutant IN is the most integrating, while the one containing the D64V mutation is the one allowing the least integration events. 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V 63;133 68;137 IN 76 78 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. To analyze the pattern of integration of WT and D167H vectors, we used genomic DNA of colonies obtained with the lower vector input (100 vRNAc/cell). 2014 Molecular therapy. Nucleic acids Result HIV D167H 48 53 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. To check whether the D167H mutant changes the kinetic of integration of HIV vectors, we transduced HEK-293T cells with WT, D167H, D64V, or D64V+D167H vectors and correlated efficiency of transduction (GFP expression) to integration (puromycin resistant clones) with time (0, 6, 12, 24, 48, and 72 hours). 2014 Molecular therapy. Nucleic acids Result HIV D167H;D167H;D167H;D64V;D64V 21;123;144;130;139 26;128;149;134;143 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. To further study if D167H mutation acts on catalytic activity of IN or through any other mechanism, we associated it with the D64V substitution that abolishes IN activity. 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V 20;126 25;130 IN;IN 65;159 67;161 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Transduction efficiency of nonintegrating mutants with 100 vRNAc/cell was much closer to that of WT and D167H (Figure 3c). 2014 Molecular therapy. Nucleic acids Result HIV D167H 104 109 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Using 10 vRNAc/cell, MFI was slightly but significantly higher after 7 days in cells transduced with D167H as compared with WT (Figure 3c). 2014 Molecular therapy. Nucleic acids Result HIV D167H 101 106 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Vector carrying IN D167H, instead, gave ~1.4 times more IS than WT vector. 2014 Molecular therapy. Nucleic acids Result HIV D167H 19 24 IN 16 18 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We asked whether HIV vectors bearing a D167H IN could improve the transduction efficiency of human hematopoietic CD34+ cells compared with WT vector. 2014 Molecular therapy. Nucleic acids Result HIV D167H 39 44 IN 45 47 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We checked whether IN mutations D64V, D167H, Q168A, LQ, or N affect functional (transducing units (TU)) or physical (capsid protein p24 or vector RNA genome (vRNAg)) properties in HIV-1 vector particles. 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V;Q168A 38;32;45 43;36;50 Capsid;p24;IN 117;132;19 123;135;21 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We observed that these forms equally decreased between 48 and 72 hours after transduction for both D167H and WT vectors (Figure 6g). 2014 Molecular therapy. Nucleic acids Result HIV D167H 99 104 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We then compared if the ratios (TU/p24) and (TU/vRNAc) were different between vectors, and only TU/vRNAc was significantly higher for D167H vector, than that of all other vector types (D167H versus: WT, D64V, Q168A, N, or LQ; P < 0.05; Supplementary Figure S1d,e). 2014 Molecular therapy. Nucleic acids Result HIV D167H;D167H;D64V;Q168A 134;185;203;209 139;191;207;214 p24 35 38 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We thus introduced the two mutations in the IN sequence of the plasmid p8.91 (p8.91-D64V+Q167H). 2014 Molecular therapy. Nucleic acids Result HIV Q167H;D64V 89;84 94;88 IN 44 46 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We transduced HEK-293T cells with 50 vRNAc of particles either carrying the single D64V or the double D64V+Q167H mutant IN. 2014 Molecular therapy. Nucleic acids Result HIV D64V;D64V;Q167H 83;102;107 87;106;112 IN 120 122 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. When comparing integration of D64V and D64V+D167H in HEK-293T cells, we observed that the more we progressed in time posttransduction, the higher the difference between the two vectors. 2014 Molecular therapy. Nucleic acids Result HIV D167H;D64V;D64V 44;30;39 49;34;43 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. With 10 vRNAc/cell, WT and D167H vectors allowed stable GFP expression over time (Figure 3a), indicating that both integrate in cell chromatin. 2014 Molecular therapy. Nucleic acids Result HIV D167H 27 32 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. A71T was found in one patient infected with a subtype C virus and A71V was found in two patients infect with subtype D. 2014 PloS one Result HIV A71V;A71T 66;0 70;4 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. A71T/V are polymorphisms that occur in 2-3% of untreated individuals but the frequency increases in patients receiving PIs. 2014 PloS one Result HIV A71V;A71T 0;0 6;6 PI 119 122 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. In subtype D isolates the frequency of polymorphism I13V was significantly lower than that found in sequences of the same subtype available in the Stanford database (Table S1). 2014 PloS one Result HIV I13V 52 56 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. In subtype F the frequency of polymorphisms A272P and I326V was significantly lower than that found in sequences of the same subtype available in the Stanford Database. 2014 PloS one Result HIV A272P;I326V 44;54 49;59 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. In the RT, we detected the K103N mutation in one patient (1/138, 0.7%) that was infected with a subtype G virus (Table S2). 2014 PloS one Result HIV K103N 27 32 RT 7 9 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. K20I was found in almost all G and CRF02_AG isolates and is a natural polymorphism of both genetic forms. 2014 PloS one Result HIV K20I 0 4 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. K20I/V codons are nonpolymorphic in most subtypes. 2014 PloS one Result HIV K20V;K20I 0;0 6;6 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. K20V was found in one patient harboring a CRF02_AG virus. 2014 PloS one Result HIV K20V 0 4 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. Similar findings were obtained for K11T, D123AS, K173S, Q174K, V179I, Q207E, R211S, T286A, E312D and G335DE in subtype A, I293V, I329L and G335D in subtype C and T200A, V292I and G335D in CRF02_AG. 2014 PloS one Result HIV D123A;D123S;E312D;G335D;G335D;G335D;G335E;I293V;I329L;K11T;K173S;Q174K;Q207E;R211S;T200A;T286A;V179I;V292I 41;41;91;101;139;179;101;122;129;35;49;56;70;77;162;84;63;169 47;47;96;107;144;184;107;127;134;39;54;61;75;82;167;89;68;174 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. Similar findings were obtained for K14R, E35D and R57K in subtype A and for L89M in subtype G. 2014 PloS one Result HIV E35D;K14R;L89M;R57K 41;35;76;50 45;39;80;54 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. The minor resistance mutations L10I and L10V, associated with resistance to most of the PIs when present with other mutations, were found in 15.7% and 17.6% of the isolates, respectively (Table S1). 2014 PloS one Result HIV L10I;L10V 31;40 35;44 PI 88 91 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. V11I, associated with resistance to darunavir, was detected in 7.7% of subtype F isolates and 13.3% of CRF02_AG isolates. 2014 PloS one Result HIV V11I 0 4 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. However four patients had diverse drug mutations combinations of K103N and V108IV (n = 1); Y184V, G190A and T215Y (n = 1); K103N, M184V and T215Y (n = 1); and A98G, Y181C (n = 1) mutations. 2014 BMC research notes Result HIV A98G;G190A;K103N;K103N;M184V;T215Y;T215Y;V108I;V108V;Y181C;Y184V 159;98;65;123;130;108;140;75;75;165;91 163;103;70;128;135;113;145;81;81;170;96 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. Of the 6 patients who harboured TAMs mutations, only 3 of them had T215Y mutations while 3 had K70R mutations among those who were on or on a previous AZT treatment. 2014 BMC research notes Result HIV K70R;T215Y 95;67 99;72 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. Single occurring mutations of V106A occurred as expected in a patient who had NVP regimen. 2014 BMC research notes Result HIV V106A 30 35 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. The K103N 11(61.1%) was most common NNRTI mutations with highest frequency occurring on EFV (n = 6; 60%) than NVP (n = 4; 40%). 2014 BMC research notes Result HIV K103N 4 9 NNRTI 36 41 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. The K65R mutation occurred in two patients without TAMs in combination with M184V mutations among those on TDF containing first-line drugs. 2014 BMC research notes Result HIV K65R;M184V 4;76 8;81 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. The most common NRTI mutation was M184V 12 (66.7%) of the 18 patients who were infected with drug resistance strains. 2014 BMC research notes Result HIV M184V 34 39 NRTI 16 20 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. These mutations were M184V (n = 1), T215Y (n = 2), V106A (n = 1), A98G (n = 1), Y18C1C (n = 1), G190A (n = 1) and V108IV (n = 1). 2014 BMC research notes Result HIV A98G;G190A;M184V;T215Y;V106A;V108I;V108V 66;96;21;36;51;114;114 70;101;26;41;56;120;120 25488402 Modulation of HIV protease flexibility by the T80N mutation. A comparison of sigma(r) for WT and T80N for the 100 ns simulations shows that at all inter-atomic vector lengths, sigma(r) is smaller for T80N than WT (Fig 7A). 2015 Proteins Result HIV T80N;T80N 36;139 40;143 25488402 Modulation of HIV protease flexibility by the T80N mutation. A comparison WAXS data collected from T80N and WT variants of HIVp reveals some significant differences in the distribution of intensities between the two samples (Fig 2). 2015 Proteins Result HIV T80N 38 42 25488402 Modulation of HIV protease flexibility by the T80N mutation. A preliminary analysis of replicated 100 ns MD runs for these two structural forms does show a greater flexibility in the simulated dynamics of WT than T80N in the majority of runs (work in progress). 2015 Proteins Result HIV T80N 152 156 25488402 Modulation of HIV protease flexibility by the T80N mutation. Additional simulations are required to know if the types of motion observed in these MD runs are sufficiently decoupled from the effects of much slower transitions to other structural states for the MD to reliably predict that the WT HIVp is more flexible than the T80N mutant. 2015 Proteins Result HIV T80N 265 269 25488402 Modulation of HIV protease flexibility by the T80N mutation. Although the resolution of molecular envelopes reconstructed from solution scattering data is limited these reconstructions are sufficient to eliminate the possibility that the T80N mutation alters HIVp dimerization or causes a conformational change in the protein outside the range expected from known crystal structures. 2015 Proteins Result HIV T80N 177 181 Env 37 46 25488402 Modulation of HIV protease flexibility by the T80N mutation. As characterized by Rg and within the error estimates for the solution scattering data, the shapes of the HIVp dimer obtained from the experimental data for WT, T80N and the protein crystal structure are indistinguishable. 2015 Proteins Result HIV T80N 161 165 25488402 Modulation of HIV protease flexibility by the T80N mutation. As forecast by the initial visual inspection of WAXS data, the WT protein appears to be much more flexible than the T80N mutant over length scales involving atomic separations up to 30 A (Fig 6). 2015 Proteins Result HIV T80N 116 120 25488402 Modulation of HIV protease flexibility by the T80N mutation. Calculations of the radii of gyration (Rg) from the x-ray scattering data give 18.47 A for WT and 18.10 A for the T80N mutant. 2015 Proteins Result HIV T80N 114 118 25488402 Modulation of HIV protease flexibility by the T80N mutation. Classifying the HIVp samples by the parameters c and e, the T80N mutant clusters with the inhibitor-bound forms rather than the functional apo forms of WT and G48V L63P (Fig 5). 2015 Proteins Result HIV G48V;L63P;T80N 159;164;60 163;168;64 25488402 Modulation of HIV protease flexibility by the T80N mutation. In contrast, in the experimentally observed scattering differences between WT and the T80N mutant the secondary maxima is almost completely eliminated from the WT data and the entire scattering pattern appears smoothed out (Fig 2). 2015 Proteins Result HIV T80N 86 90 25488402 Modulation of HIV protease flexibility by the T80N mutation. In order to identify any large conformational differences between HIVp structures in solution, low-resolution reconstructions of the molecular envelopes were calculated from the solution scattering data from both the WT and T80N samples using ab initio (model independent) methods . 2015 Proteins Result HIV T80N 224 228 Env 143 152 25488402 Modulation of HIV protease flexibility by the T80N mutation. MD simulations were carried out for both WT and T80N HIVp as previously described . 2015 Proteins Result HIV T80N 48 52 25488402 Modulation of HIV protease flexibility by the T80N mutation. Rather than simply providing a local effect on the mobility of the flaps, the effect of the T80N mutation is to cause a general increase in the rigidity of the protein through the entire structure. 2015 Proteins Result HIV T80N 92 96 25488402 Modulation of HIV protease flexibility by the T80N mutation. Since both the WT and T80N simulations were started from the same well-equilibrated structure, this pair of 100 ns simulations compares the ambient dynamics of these proteins in the conformational region of this starting point. 2015 Proteins Result HIV T80N 22 26 25488402 Modulation of HIV protease flexibility by the T80N mutation. Solution scattering data were collected from a series of HIVp variants which included: WT, T80N, and the flap variant G48V that included the secondary mutation L63P. 2015 Proteins Result HIV G48V;L63P;T80N 118;160;91 122;164;95 25488402 Modulation of HIV protease flexibility by the T80N mutation. The addition of inhibitor to T80N has very little effect on the parameters representing protein flexibility. 2015 Proteins Result HIV T80N 29 33 25488402 Modulation of HIV protease flexibility by the T80N mutation. The addition of pepstatin inhibitor to either WT or the G48V/L63P mutant results in a large reduction in the flexibility of these proteins such that they approach the reduced levels of motion observed for the T80N mutant. 2015 Proteins Result HIV G48V;L63P;T80N 56;61;209 60;65;213 25488402 Modulation of HIV protease flexibility by the T80N mutation. The impact of the T80N point mutation is to reduce the protease flexibility so that it resembles the inhibitor-bound states. 2015 Proteins Result HIV T80N 18 22 PR 55 63 25488402 Modulation of HIV protease flexibility by the T80N mutation. The main focus of this work is elucidating the mechanism by which the T80N variant is inactive compared to WT. 2015 Proteins Result HIV T80N 70 74 25488402 Modulation of HIV protease flexibility by the T80N mutation. The quantification of protein flexibility provided in Table 1 shows that, on average, the distances between atom pairs separated by 10 A fluctuate by ~2 A in the T80N mutant and the magnitude of this fluctuation is ~ 0.8 A greater in WT. 2015 Proteins Result HIV T80N 162 166 25488402 Modulation of HIV protease flexibility by the T80N mutation. The scattering pattern from the T80N variant shows sharper features than the WT, indicating a more rigid protein structure. 2015 Proteins Result HIV T80N 32 36 25488402 Modulation of HIV protease flexibility by the T80N mutation. These structural results are consistent with other experimental data, including CD measurements and tryptophan fluorescence spectra, which also indicate a very high degree of similarity between the T80N and WT structures either in the presence or in the absence of ligand . 2015 Proteins Result HIV T80N 198 202 25488402 Modulation of HIV protease flexibility by the T80N mutation. Vector-length convolution calculations were carried out to fit WAXS patterns from WT, T80N, and G48V/L63P HIVp variants using data from protein both in the presence and absence of inhibitor. 2015 Proteins Result HIV G48V;L63P;T80N 96;101;86 100;105;90 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. As shown in Figure 10, all WT viruses cause a cytopathic effect in the monolayer while most mutant viruses do not visibly affect the architecture of the monolayer, except N616Q HIV-1ADA that was able to cause cytopathic effects similar to WT HIV-1ADA, which is in agreement with the flow cytometry results (Figure 9B). 2014 Retrovirology Result HIV N616Q 171 176 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. As shown in Figure 11, severely decreased gp120 levels were found for mutant N616Q gp41 HIV-1 strains NL4.3, IIIB and HE. 2014 Retrovirology Result HIV N616Q 77 82 gp120;gp41 42;83 47;87 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Based on the microscopic observations, no marked differences between infection with WT virus and infection with the gp41 glycan-deleted mutants N625Q, N637Q and N674Q gp41 HIV-1 strains could be observed. 2014 Retrovirology Result HIV N625Q;N637Q;N674Q 144;151;161 149;156;166 gp41;gp41 116;167 120;171 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Based on the observation that HIV-1NL4.3 containing the gp41 N616Q glycan deletion had a severely decreased viral infectivity (Figures 2, 3, 9) due to significantly decreased levels of gp120 and gp41 in the viral envelope (Figure 5), we studied the gp120 levels in the other WT and N616Q mutant HIV-1 strains. 2014 Retrovirology Result HIV N616Q 282 287 Env;gp120;gp120;gp41;gp41 213;185;249;56;195 221;190;254;60;199 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Figure 7A shows that the N611Q and N625Q mutant gp41 virus strains were endowed with a capture efficiency not significantly different from WT virus. 2014 Retrovirology Result HIV N611Q;N625Q 25;35 30;40 gp41 48 52 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Figure 7B shows that mutant virus strains containing the N625Q and N637Q mutations in gp41 had transmission efficiencies equal to WT virus. 2014 Retrovirology Result HIV N625Q;N637Q 57;67 62;72 gp41 86 90 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. However, during the selection of HHA/2G12 resistant virus we obtained a gp41 N-glycan deletion due to the N674D mutation, altering the asparagine into an aspartic acid. 2014 Retrovirology Result HIV N674D 106 111 gp41 72 76 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. However, infection with mutant N611Q gp41 HIV-1 resulted in a marked decrease in both giant cell formation and eGFP expression. 2014 Retrovirology Result HIV N611Q 31 36 gp41 37 41 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. However, the gp41 mutant N625Q showed a non-significant increase (~130% of WT) in binding efficiency. 2014 Retrovirology Result HIV N625Q 25 30 gp41 13 17 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. In contrast, it was shown that the N616Q mutation in HIV-1ADA had much more modest suppressive effects on viral infectivity (not significant). 2014 Retrovirology Result HIV N616Q 35 40 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. In contrast, the N616Q gp41 mutant HIV-1ADA showed gp120 levels that were comparable to the levels observed in WT HIV-1ADA. 2014 Retrovirology Result HIV N616Q 17 22 gp120;gp41 51;23 56;27 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. In Figure 3, similar results were obtained for the N674Q mutant, which also showed a non-significant increase in viral infectivity. 2014 Retrovirology Result HIV N674Q 51 56 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. It could be shown that the gp41 mutant N611Q, N637Q and N674Q HIV-1 strains had a binding efficiency to soluble CD4 (sCD4) that was not markedly different from WT virus. 2014 Retrovirology Result HIV N611Q;N637Q;N674Q 39;46;56 44;51;61 gp41 27 31 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. It was shown that all mutants except for the N616Q mutant contained marked levels of gp120 and gp41 in their envelope that were not significantly different from the levels in WT virus. 2014 Retrovirology Result HIV N616Q 45 50 Env;gp120;gp41 109;85;95 117;90;99 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. It was shown that the deletion of the N616Q glycan resulted in a severe decrease in viral infectivity of HIV-1NL4.3, HIV-1IIIB and HIV-1HE in C8166 cells (Figure 9A). 2014 Retrovirology Result HIV N616Q 38 43 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. No combinations were made involving the N616Q glycan in this study since this would most likely result in uninfectious virus strains. 2014 Retrovirology Result HIV N616Q 40 45 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The effect of the N616Q glycan deletion in gp41 on the infectivity and gp120 envelope levels of various HIV-1 strains. 2014 Retrovirology Result HIV N616Q 18 23 Env;gp120;gp41 77;71;43 85;76;47 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The effect of the N674D mutation in HIV-1 gp41. 2014 Retrovirology Result HIV N674D 18 23 gp41 42 46 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The gp41 HIV-1 mutants N611Q and N637Q also proved to have a decreased viral infectivity, which was only significant for mutant N611Q. 2014 Retrovirology Result HIV N611Q;N611Q;N637Q 23;128;33 28;133;38 gp41 4 8 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The gp41 mutant N616Q HIV-1 strain was seemingly without any viral infectivity potential. 2014 Retrovirology Result HIV N616Q 16 21 gp41 4 8 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The maximal level of resistance observed was 3.1 for HHA (strain N611Q/N637Q/N674Q) and 2.5 for UDA (strain N611Q/N637Q). 2014 Retrovirology Result HIV N611Q;N637Q;N674Q;N611Q;N637Q 65;71;77;108;114 70;76;82;113;119 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The mutant N616Q, which was earlier shown to be uninfectious, was found to have a significantly decreased CD4 binding (~5% of WT). 2014 Retrovirology Result HIV N616Q 11 16 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The mutant N674Q virus strain had an increased transmission efficiency, while the mutant N611Q showed a highly decreased transmission efficiency. 2014 Retrovirology Result HIV N611Q;N674Q 89;11 94;16 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The N616Q gp41 mutation resulted in a complete absence of virus transmission, which is consistent with the finding that this mutation was also highly detrimental on virus infectivity, CD4 binding and envelope glycoprotein expression. 2014 Retrovirology Result HIV N616Q 4 9 Env;gp41 200;10 208;14 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The N674D gp41 mutation resulted in an increased viral infectivity (although not significant) (Figure 13). 2014 Retrovirology Result HIV N674D 4 9 gp41 10 14 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The N674D mutation in gp41 was shown to have minor effects on CBA susceptibility (Table 3). 2014 Retrovirology Result HIV N674D 4 9 gp41 22 26 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The other mutants (N625Q and N674Q) had a viral infectivity not different from WT virus. 2014 Retrovirology Result HIV N625Q;N674Q 19;29 25;34 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Therefore, we generated additional N616Q gp41 mutant virus strains. 2014 Retrovirology Result HIV N616Q 35 40 gp41 41 45 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. These results differ somewhat from the results obtained with the N674Q gp41 HIV-1 mutant (Table 2). 2014 Retrovirology Result HIV N674Q 65 70 gp41 71 75 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. This explains why the N616Q glycan deletion in gp41 of HIV-1ADA did not result in a loss of viral infectivity. 2014 Retrovirology Result HIV N616Q 22 27 gp41 47 51 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. To determine the possible effect of this glycan deletion, we generated a mutant HIV-1NL4.3 strain containing the N674D mutation in gp41 and investigated the effect of this mutation on viral infectivity and CBA susceptibility. 2014 Retrovirology Result HIV N674D 113 118 gp41 131 135 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. While the N674Q gp41 HIV-1 mutant was slightly phenotypically resistant towards these compounds, the N674D mutation rather increased the susceptibility of the mutant virus towards these compounds. 2014 Retrovirology Result HIV N674D;N674Q 101;10 106;15 gp41 16 20 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Although the RC of HIV-M184V and HIV-M184I is decreased in primary T cells, we have previously shown that the RC of the mutants is similar to HIV-WT in a T cell line. 2014 Retrovirology Result HIV M184I;M184V 37;23 42;28 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. DCs from three different donors were infected with a mixture of HIV-WT and HIV-M184T, and their relative replication capacity was determined by analysis of their frequency in the viral population over time. 2014 Retrovirology Result HIV M184T 79 84 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Furthermore, HIV-WT was also able to produce more virus than HIV-M184T as determined by HIV-CA (p24) ELISA of in the supernatant (3 donors, Figure 6B). 2014 Retrovirology Result HIV M184T 65 70 p24;Capsid 96;92 99;94 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. HIV-M184V, -I and -T (combined: HIV-M184 variants) were less efficiently transmitted by LCs to T cells than the HIV-WT, whereas the level of transmission of HIV-K103N was intermediate (n=3 donors, Figure 1A). 2014 Retrovirology Result HIV K103N;M184V 161;4 166;9 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. In line with the results obtained with CCR5+ Jurkat T cells, HIV-M184 variants and HIV-K103N were less efficiently transmitted by LCs than HIV-WT. 2014 Retrovirology Result HIV K103N 87 92 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. It was shown that HIV-WT rapidly outcompeted HIV-M184T, confirming the low RC of HIV-M184T in DCs (3 donors, Figure 7). 2014 Retrovirology Result HIV M184T;M184T 49;85 54;90 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. RT-qPCR on intracellular RNA demonstrated that HIV-WT was able to transcribe a higher amount of the viral mRNA Tat-Rev (3 donors, Figure 6A) than HIV-M184T. 2014 Retrovirology Result HIV M184T 150 155 Rev;Tat;RT 115;111;0 118;114;2 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The infection rate of HIV-K103N was higher than to HIV-WT, which is in agreement with the observed transmission data (Figure 5). 2014 Retrovirology Result HIV K103N 26 31 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The RC of HIV-M184T is even more impaired than the RC of M184V/I, and as such this variant is rarely observed in vivo but can be selected in vitro. 2014 Retrovirology Result HIV M184I;M184T;M184V 57;14;57 64;19;64 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The transmission efficacy of LCs and DCs to TZM-bl target cells was also comparable to the CCR5+ Jurkat T cells; the HIV-M184 variants were less frequently transmitted as HIV-WT and the HIV-K103N transmission efficacy was comparable to HIV-WT (Figure 3B-C). 2014 Retrovirology Result HIV K103N 190 195 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The transmission rate of HIV-K103N was even higher than HIV-WT in all but one experiment (Figure 2A). 2014 Retrovirology Result HIV K103N 29 34 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Therefore, we compared the transmission efficacy of HIV-M184V/I to HIV-WT and HIV-K103N. 2014 Retrovirology Result HIV K103N;M184I;M184V 82;56;56 87;63;63 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. To gain more insight in the impact of RC on transmission efficacy, we additionally investigated the drug resistant HIV-M184T variant. 2014 Retrovirology Result HIV M184T 119 124 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. We hypothesized that due to a diminished replication potential, HIV harboring M184V/I is less efficiently transmitted than HIV-WT or drug resistant virus variants with a high RC. 2014 Retrovirology Result HIV M184I;M184V 78;78 85;85 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Among CRF07_BC recombinant strains, 21.0% (13/62) had TDR-associated mutations, A71T/V being the most frequent. 2014 BMC infectious diseases Result HIV A71T;A71V 80;80 86;86 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Among subtype B, 54.5% (12/22) had TDR-associated mutations, A71T/V and V106I being the most frequent. 2014 BMC infectious diseases Result HIV A71T;A71V;V106I 61;61;72 67;67;77 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Among these detected mutations, only L74I, M46L, G190E and E138G may result in drug resistance directly. 2014 BMC infectious diseases Result HIV E138G;G190E;L74I;M46L 59;49;37;43 64;54;41;47 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Eight mutation pairs with significant co-variation were identified in the RT region for CRF01_AE strains between the V179D/E TDR-associated mutation and seven overlapping polymorphisms. 2014 BMC infectious diseases Result HIV V179D;V179E 117;117 124;124 RT 74 76 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. PI mutations included L10I/V (7.2%, 16/223) and A71L/T/V (6.3%, 14/223), with relatively high frequency; NRTI mutations, included L74I (0.45%, 1/223) and V75L (0.45%, 1/223); and the most frequent NNRTI mutation was V179D/E (5.4%, 12/223). 2014 BMC infectious diseases Result HIV A71L;A71T;A71V;L10I;L10V;L74I;V179D;V179E;V75L 48;48;48;22;22;130;216;216;154 56;56;56;28;28;134;223;223;158 NNRTI;NRTI;PI 197;105;0 202;109;2 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. The proportion of TDR-associated mutations was 23.7% (32/135) among CRF01_AE recombinant strains, the most frequent mutations being L10I/V and V179D/E. 2014 BMC infectious diseases Result HIV L10I;L10V;V179D;V179E 132;132;143;143 138;138;150;150 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Additionally, due to a 1.0 A movement of the side chain of Leu38, the upper elbow composed of residues 35-40 is displaced downward as a result of the acquisition of new vdw interactions between the side chain of Leu38 and neighboring residues, Tyr59 and Ile15, in PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 271 275 PR 264 266 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Additionally, PRG48T/L89M-SQV exhibits an increase in distance between Gly51 and Gly52' from 4.0 to 4.7 A, resulting in the loss of a vdw contact between these residues. 2015 Biochemistry Result HIV L89M 21 25 PR 14 16 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Additionally, the hydrogen bond between Asp30 and ND2 of the P2 Asn is stronger in PRG48T/L89M-SQV (3.0 A) compared to PRWT-SQV (3.8 A). 2015 Biochemistry Result HIV L89M 90 94 Asp;PR 40;83 43;85 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Also, in PRG48T/L89M-SQV, active site expansion is apparent in the 80's loop relative to PRWT-SQV. 2015 Biochemistry Result HIV L89M 16 20 PR 9 11 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Also, PRG48T/L89M-SQV contains the natural polymorphism, Val3Ile. 2015 Biochemistry Result HIV L89M;V3I 13;57 17;64 PR 6 8 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Also, the solvent-mediated interaction between ND2 of SQV and N1-H of SQV is not present in the PRG48T/L89M-SQV complex. 2015 Biochemistry Result HIV L89M 103 107 PR 96 98 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Also, there is an increase in distance between the side chains of Ile54 and Gly51' in PRG48T/L89M-SQV (4.4 A) compared to PRWT-SQV (3.8 A) resulting in the former in a loss of a vdw interaction between the flaps of monomer A and B. 2015 Biochemistry Result HIV L89M 93 97 PR 86 88 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Alterations in the arrangement of vdw interactions are observed between PRWT-SQV and PRG48T/L89M-SQV, and we speculate that this may interfere with the hydrophobic sliding mechanism resulting in the inability of PRG48T/L89M-SQV to achieve a fully closed conformation. 2015 Biochemistry Result HIV L89M;L89M 92;219 96;223 PR;PR 85;212 87;214 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Although one contact is retained between Ile15' and Leu33' in PRG48T/L89M-SQV, the net loss of two vdw contacts between Ile13'/15' and Leu33' results in a destabilized 30's and 'teens strands. 2015 Biochemistry Result HIV L89M 69 73 PR 62 64 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Another difference in PRG48T/L89M-SQV, is that one of the two alternative routes of vdw forces that lead back to Leu89 that link the fulcrum to the rest of the mechanism is missing due to the lost vdw interaction between Ile13 and Ile66. 2015 Biochemistry Result HIV L89M 29 33 PR 22 24 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Another two vdw contacts are lost in PRG48T/L89M-SQV between Ile50 and Thr48' where the distance between these residues has changed from 3.3 and 3.9 A in PRWT-SQV to 4.5 and 5.1 A, respectively, in PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M;L89M 44;205 48;209 PR;PR 37;198 39;200 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. As for Gln2', its 45 rotation in PRG48T/L89M-SQV results in a new hydrogen bond (3.2 A) between the Oepsilon of Gln2' and the Ogamma-H of Thr96. 2015 Biochemistry Result HIV L89M 41 45 PR 34 36 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. As for the elbow flaps, in PRWT-SQV a vdw interaction between Leu38' in the elbow flap and Met36' is lost (6.2 A) in PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 124 128 PR 117 119 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Assessment of the steady-state binding kinetics and catalytic turnover of the chromogenic decapeptide substrate, Lys-Ala-Arg-Val-Leu*Nph-Glu-Ala-NLe-Gly, reveals that the Gly48Thr/Leu89Met mutations and the natural polymorphism, Val3Ile, do not affect the kinetic parameters Km, kcat, or the overall catalytic efficiency of the enzyme, kcat/Km, compared to PRWT (Table 3). 2015 Biochemistry Result HIV G48T;L89M;V3I 171;180;229 179;188;236 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. At first glance there are noticeable differences between the 19 hydrophobic core residues in monomer A compared to monomer B of PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 135 139 PR 128 130 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Comparison of the active site volumes of PRG48T/L89M-SQV (1250 A3) and PRWT-SQV (1100 A3) indicates that the active site of PRG48T/L89M-SQV has increased 13% relative to PRWT-SQV. 2015 Biochemistry Result HIV L89M;L89M 48;131 52;135 PR;PR 41;124 43;126 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Consequently, the horizontally sliding of the fulcrum over the 30's strand may be impaired in PRG48T/L89M-SQV, thus preventing complete flap closure. 2015 Biochemistry Result HIV L89M 101 105 PR 94 96 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Consequently, this would provide an explanation for the weaker inhibitor binding observed with several of the FDA approved inhibitors tested with PRG48T/L89M. 2015 Biochemistry Result HIV L89M 153 157 PR 146 148 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Defective Horizontal Hydrophobic Sliding in PRG48T/L89M-SQV: Monomer B. 2015 Biochemistry Result HIV L89M 51 55 PR 44 46 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Defective Vertical Hydrophobic Sliding in PRG48T/L89M-SQV: Monomer B. 2015 Biochemistry Result HIV L89M 49 53 PR 42 44 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Effect of Gly48Thr/Leu89Met on Substrate and Inhibitor Binding. 2015 Biochemistry Result HIV G48T;L89M 10;19 18;27 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Effect of Substitution Leu89Met on the Hydrophobic Core. 2015 Biochemistry Result HIV L89M 23 31 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Examination of other contacts important for dimerization reveals an 86 rotation of the side chain of Arg8 in PRG48T/L89M-SQV resulting in two new hydrogen bonds between Arg8 and Asp29'. 2015 Biochemistry Result HIV L89M 117 121 Asp;PR 179;110 182;112 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Exploration of the role of Met89' in monomer B of PRG48T/L89M-SQV (Figure 5B) reveals quite interesting differences compared to PRWT-SQV, described previously. 2015 Biochemistry Result HIV L89M 57 61 PR 50 52 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. First, there is a loss of important vdw interactions in PRG48T/L89M-SQV compared to PRWT-SQV. 2015 Biochemistry Result HIV L89M 63 67 PR 56 58 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. For example, the Leu89Met mutation is at 1 of the 19 amino acid positions that comprises the hydrophobic core of the protease. 2015 Biochemistry Result HIV L89M 17 25 PR 117 125 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Glu35 and Arg8 are the only residues that show partial occupancy in PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 75 79 PR 68 70 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. However, in PRG48T/L89M-SQV the side chain of Val82' is relocated 156 away from the P1 Phe of SQV and the guinidinium group of Arg8' is rotated 117 away from the active site. 2015 Biochemistry Result HIV L89M 19 23 PR 12 14 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. However, in the PRG48T/L89M-SQV structure the Cgamma1 of Val82' makes only two vdw contacts with the P1 Phe, thus resulting in the loss of three vdw contacts between the P1 Phe of SQV and S1 of PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M;L89M 23;201 27;205 PR;PR 16;194 18;196 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. However, in three tandem locations within the flaps of PRG48T/L89M-SQV vdw contacts are lost. 2015 Biochemistry Result HIV L89M 62 66 PR 55 57 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. However, this is not the case in PRG48T/L89M-SQV where Leu33' has lost all vdw contacts with Ile13' (4.8 A) and only has one remaining vdw contact with Ile15' (3.8 A). 2015 Biochemistry Result HIV L89M 40 44 PR 33 35 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. However, when exploring the vdw interactions involving these residues in PRWT-SQV and PRG48T/L89M-SQV we do uncover interesting similarities and differences that provide illuminating insights on the sliding mechanism of these constructs. 2015 Biochemistry Result HIV L89M 93 97 PR 86 88 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. IDV exhibited the greatest loss of binding potency for PRG48T/L89M with a 41-fold increase in Ki relative to PRWT, followed by SQV (18-fold) (Figure 2), APV (15-fold), and NFV (9-fold). 2015 Biochemistry Result HIV L89M 62 66 PR 55 57 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In addition, a new solvent-mediated interaction is observed in the PRG48T/L89M-SQV complex between the amide N of Asp29' and N3 of SQV. 2015 Biochemistry Result HIV L89M 74 78 Asp;PR 114;67 117;69 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In monomer A of PRG48T/L89M-SQV, the downward displacement of the elbow composed of residues 16-19 is a result of the approximate 180 repositioning of Gln18 (Figure 3A). 2015 Biochemistry Result HIV L89M 23 27 PR 16 18 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In other words, PRG48T/L89M-SQV has lost important vdw interactions that facilitate the horizontal hydrophobic sliding of the fulcrum and 30's strand and has acquired many new vdw forces linking the 'teens strand of the fulcrum to the cantilever. 2015 Biochemistry Result HIV L89M 23 27 PR 16 18 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In PRG48T/L89M-SQV, Val75' does not make a vdw contact with Ile64' (5.8 A). 2015 Biochemistry Result HIV L89M 10 14 PR 3 5 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In regard to the vertical sliding of the cantilever against the fulcrum in PRG48T/L89M-SQV, Met89' owing to its longer side chain bypasses Thr31' and makes a vdw contact with Val75' in the cantilever. 2015 Biochemistry Result HIV L89M 82 86 PR 75 77 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In summation of the interactions in the terminal domain, two new interdomain hydrogen bonds and three new vdw contacts are gained in this region of the dimerization domain in PRG48T/L89M-SQV, thus contributing to a more stable dimer relative to PRWT-SQV. 2015 Biochemistry Result HIV L89M 182 186 PR 175 177 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In support of this, our molecular dynamics simulations also indicate that the flaps of PRG48T/L89M-SQV are more flexible than PRWT-SQV (Figure 4B and C) and assume a more open conformation compared to PRWT-SQV (Supporting Information Figure S2). 2015 Biochemistry Result HIV L89M 94 98 PR 87 89 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In the PRG48T/L89M-SQV complex, the hydrogen bond from the carbonyl of Gly48 to N1-H of the quinolone ring is missing and accounts for the torqueing of the quinolone ring system (Figure 6A and Supporting Information Figure S5). 2015 Biochemistry Result HIV L89M 14 18 PR 7 9 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In the S2' pocket, one vdw interaction between the tert-butyl of SQV and Ala28' is lost (4.1 A vs 4.9 A) in PRG48T/L89M-SQV which may account for its 33 rotation (data not shown) and further enlargement of the active site. 2015 Biochemistry Result HIV L89M 115 119 PR 108 110 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Inspection of this region (Supporting Information Figure S1) reveals rotations of the side chains of Gln2 and Asn98' in PRG48T/L89M-SQV that results in an angle suitable for a new hydrogen bond (2.9 A) between the Oepsilon of Gln2 and the deltaN-H of Asn98'. 2015 Biochemistry Result HIV L89M 127 131 PR 120 122 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Instead, in PRG48T/L89M-SQV Ile13' and Ile15' make nine vdw contacts between Ile64' and Ile66' which are located in the cantilever. 2015 Biochemistry Result HIV L89M 19 23 PR 12 14 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. It appears that the horizontal hydrophobic sliding mechanism in monomer A of PRG48T/L89M-SQV is similar to that of monomer A of PRWT-SQV, since vdw contacts between Leu33 and Ile13/Ile15 are conserved between the two structures. 2015 Biochemistry Result HIV L89M 84 88 PR 77 79 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. It should be noted that these simulations were done with unliganded PR, so a direct comparison with PRWT-SQV and PRG48T/L89M-SQV is not possible. 2015 Biochemistry Result HIV L89M 120 124 PR;PR 68;113 70;115 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. It should be noted that two vdw contacts are gained in PRG48T/L89M-SQV between Ile54' and Ile50. 2015 Biochemistry Result HIV L89M 62 66 PR 55 57 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Like PRWT-SQV, Met89 interacts with Val75; however, it bypasses Thr31, like in monomer B of PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 99 103 PR 92 94 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Like the terminal region of the dimerization domain, additional hydrogen bonding interactions are detected in this region of PRG48T/L89M-SQV indicating increased dimer stability. 2015 Biochemistry Result HIV L89M 132 136 PR 125 127 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Modified Hydrophobic Sliding in Monomer A: PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 50 54 PR 43 45 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Neither structure contains stabilizing mutations Gln7Lys, Leu33Ile, or Leu63Ile. 2015 Biochemistry Result HIV L33I;L63I;Q7K 58;71;49 66;79;56 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Nine FDA approved clinical PR inhibitors were evaluated for their binding potency for PRWT and PRG48T/L89M (Table 2). 2015 Biochemistry Result HIV L89M 102 106 PR;PR 27;95 29;97 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Our molecular dynamics simulations indicate that saquinavir is more mobile in the active site of PRG48T/L89M-SQV (Supporting Information Figure S4) compared to PRWT-SQV and that SQV makes less favorable vdw interactions with the active site residues Ile50, Phe53, Val82, Ile84, and Ala28' of PRG48T/L89M-SQV compared to PRWT-SQV (Supporting Information Figure S6). 2015 Biochemistry Result HIV L89M;L89M 104;299 108;303 PR;PR 97;292 99;294 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. PRG48T/L89M-SQV exhibits a downward displaced fulcrum relative to the more "closed" form of PRWT-SQV. 2015 Biochemistry Result HIV L89M 7 11 PR 0 2 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Second, there is the formation of new interactions between alternate strands of the sliding mechanism in PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 112 116 PR 105 107 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Structural Effects of Gly48Thr/Leu89Met Mutations. 2015 Biochemistry Result HIV G48T;L89M 22;31 30;39 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Superposition of the crystal structures for PRG48T/L89M-SQV and PRWT-SQV shows the consequences of the defective sliding mechanism of PRG48T/L89M-SQV (Figure 1C). 2015 Biochemistry Result HIV L89M;L89M 51;141 55;145 PR;PR 44;134 46;136 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The crystal structure of PRG48T/L89M complexed with SQV has been determined to a resolution of 1.9 A (PDB ID code 4QGI) (Figure 1C). 2015 Biochemistry Result HIV L89M 32 36 PR 25 27 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The effect of the Leu89Met substitution on hydrophobic sliding is less noticeable in monomer A which is consistent with its less severe structural perturbations (Supporting Information Figure S3B). 2015 Biochemistry Result HIV L89M 18 26 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The increased number of vdw forces between the fulcrum and the cantilever (3 vdw contacts in PRWT-SQV vs 9 vdw contacts in PRG48T/L89M-SQV) may result in the inability of the cantilever to slide properly, thus preventing complete flap closure. 2015 Biochemistry Result HIV L89M 130 134 PR 123 125 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The interdomain hydrogen bonding interactions between Arg87 and the carbonyl oxygen of Leu5 are conserved from PRWT-SQV to PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 130 134 PR 123 125 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The Leu89Met substitution in monomer B appears to have perturbed the hydrophobic sliding mechanism as a result of two effects. 2015 Biochemistry Result HIV L89M 4 12 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The linkage of vdw forces in the cantilever from Val75' to Ile64', then to Ile66', and then back to Met89' is notably different in PRG48T/L89M-SQV compared to PRWT-SQV. 2015 Biochemistry Result HIV L89M 138 142 PR 131 133 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The only differences in the amino acid sequences of PRG48T/L89M-SQV compared to PRWT-SQV are that the former contains the natural polymorphism Val3Ile in addition to the mutations. 2015 Biochemistry Result HIV L89M;V3I 59;143 63;150 PR 52 54 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The overall consequence of the Gly48Thr/Leu89Met mutations is a loss of vdw interactions that results in weaker interatomic flap interactions. 2015 Biochemistry Result HIV G48T;L89M 31;40 39;48 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The P2 Asn exhibits more favorable interactions with PRG48T/L89M-SQV compared to its binding motif in PRWT-SQV. 2015 Biochemistry Result HIV L89M 60 64 PR 53 55 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The PRG48T/L89M-SQV structure was determined in the space group P212121 and compared to the previously determined structure of PR bound with SQV (resolution: 2.3 A; space group P61; PDB code 1HXB) (PRWT-SQV). 2015 Biochemistry Result HIV L89M 11 15 PR;PR 4;127 6;129 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The repositioning of Val82' results in the opening of the base of the S1/S3 subsite in the PRG48T/L89M-SQV structure (Figure 6 A,B,C). 2015 Biochemistry Result HIV L89M 98 102 PR 91 93 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The S3 subsite is directly impacted by the Gly48Thr substitution in monomer A. 2015 Biochemistry Result HIV G48T 43 51 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The same acquisition of two hydrogen bonds between the two dimers is observed between Arg8' and Asp29 in PRG48T/L89M-SQV, due to a 117 rotation of Arg8'. 2015 Biochemistry Result HIV L89M 112 116 Asp;PR 96;105 99;107 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. These alterations in vdw interactions likely play a role in the repositioning of the elbow flap downward, thus favoring a more open conformation of PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 155 159 PR 148 150 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. These data agree with our crystallographic observations of an expanded active site that results in the loss of important interactions between SQV and the S1, S3, and S2' subsites of PRG48T/L89M-SQV. 2015 Biochemistry Result HIV L89M 189 193 PR 182 184 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. These vdw forces are significantly altered in PRG48T/L89M-SQV and may account for a defective hydrophobic sliding mechanism. 2015 Biochemistry Result HIV L89M 53 57 PR 46 48 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. This contributes to the weaker binding of SQV observed with PRG48T/L89M-SQV and importantly an enlarged active site. 2015 Biochemistry Result HIV L89M 67 71 PR 60 62 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. This is supported by molecular dynamics simulations showing increased mobility of SQV in the active site of PRG48T/L89M-SQV relative to PRWT-SQV. 2015 Biochemistry Result HIV L89M 115 119 PR 108 110 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. This is supported by molecular dynamics simulations that indicate that the cantilever of PRG48T/L89M-SQV is more rigid compared to PRWT-SQV (Figure 4B,C). 2015 Biochemistry Result HIV L89M 96 100 PR 89 91 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). A derivative of pNL4-3uncFL in which the substitution at position 40 of p6Gag was reversed to the wild-type Ser-codon while retaining all other substitutions (pNL4-3uncFL-N40S) was also included (Figure 1A). 2014 Retrovirology Result HIV N40S 171 175 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Furthermore, enhanced membrane binding affinity of a synthetic p6 C-terminal fragment was observed in vitro upon substitution of Ser40 by Phe or upon adding a phosphate group to this residue. 2014 Retrovirology Result HIV S40F 129 141 Gag 63 65 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Furthermore, we did not observe a block in Vpr incorporation upon mutation of S40, which had been reported for an S40A variant in a previous study and had been proposed to result in impaired replication in primary macrophages. 2014 Retrovirology Result HIV S40A 114 118 Vpr 43 46 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). However, wild-type release, polyprotein processing and infectivity of all variants studied here except for S40F suggest that neither S40 nor its phosphorylation is needed for fully functional membrane binding of Gag. 2014 Retrovirology Result HIV S40F 107 111 Gag 212 215 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). In contrast, previous studies had reported that an S40F change in p6Gag impaired proteolytic maturation of Gag, reduced viral infectivity and delayed replication in T-cell lines. 2014 Retrovirology Result HIV S40F 51 55 Gag 107 110 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). In line with published results, infectivity was severely decreased for the S40F variant with a similar reduction as observed for the release deficient late(-) control. 2014 Retrovirology Result HIV S40F 75 79 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). In summary, our analyses confirm previous reports that an S40F substitution in p6Gag of HIV-1 impairs Gag processing at the CA-SP1 site and severely affects or abolishes HIV-1 replication in cell lines and primary cells. 2014 Retrovirology Result HIV S40F 58 62 SP1;Gag;Capsid 127;102;124 130;105;126 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Increased amounts of the CA-SP1 processing intermediate were observed in case of the S40F variant, consistent with previous reports, and particle release was also slightly higher in this case (Figure 1B,C). 2014 Retrovirology Result HIV S40F 85 89 SP1;Capsid 28;25 31;27 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Kudoh and coworkers reported that (i) an S40A substitution in p6Gag abolished incorporation of exogenously expressed Vpr into virus-like Gag particles (VLPs) and (ii) a PKC inhibitor, presumed to prevent phosphorylation of S40, impaired HIV-1 replication in primary macrophages. 2014 Retrovirology Result HIV S40A 41 45 Vpr;Gag 117;137 120;140 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Most importantly, however, replication kinetics of the S40N, FL, and FL-N40S variants in PBMC were indistinguishable from wild-type HIV-1NL4-3unc (Figure 4A, B), demonstrating that the serine residue itself and phosphorylation at this site are both dispensable for HIV-1 replication in primary T-cells. 2014 Retrovirology Result HIV N40S;S40N 72;55 76;59 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Neither single-round infectivity nor viral titer of the variants HIV-1NL4-3uncFL, FL-N40S, or S40N, respectively, differed significantly from that of wild-type HIV-1NL4-3unc (Figure 3A,B). 2014 Retrovirology Result HIV N40S;S40N 85;94 89;98 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Our analysis further revealed that neither the S40F nor the S40N exchange altered Vpr incorporation into HIV-1 (Figure 2). 2014 Retrovirology Result HIV S40F;S40N 47;60 51;64 Vpr 82 85 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Replication of the late(-) (Figure 4A) and S40F variants (Figure 4B) was completely abolished in PBMC, consistent with their severe replication defect in established cell lines. 2014 Retrovirology Result HIV S40F 43 47 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). The replication defect of the S40F mutant in PBMCs was even more severe than in a previous report analyzing replication in primary human lymphocyte aggregate cultures, where residual and delayed replication had been observed. 2014 Retrovirology Result HIV S40F 30 34 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). The S40F exchange was furthermore shown to result in an enhanced interaction of Gag with the ESCRT-associated protein Alix. 2014 Retrovirology Result HIV S40F 4 8 Gag 80 83 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Thus, the previously described replication defect of the S40F variant appears to be due to the replacement of the small, hydrophilic serine by a bulky hydrophobic phenylalanine residue, rather than indicating a requirement for S40. 2014 Retrovirology Result HIV S40F 57 61 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). Variants NL4-3uncFL, FL-N40S, and S40N displayed wild-type Gag processing and particle release. 2014 Retrovirology Result HIV N40S;S40N 24;34 28;38 Gag 59 62 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). We conclude that the Vpr incorporation block reported before is either a specific property of the S40A variant, or, more likely, represents a feature of the Gag/Vpr overexpression system used in the prior study that is not observed in the native viral context. 2014 Retrovirology Result HIV S40A 98 102 Vpr;Vpr;Gag 21;161;157 24;164;160 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). We did not analyze Gag membrane-binding properties, which had been reported to be affected by the S40F substitution or by introducing a phosphomimick in this position. 2014 Retrovirology Result HIV S40F 98 102 Gag 19 22 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. For the infant with K103N, detected by bulk sequencing, both Ion PGM and MiSeq additionally detected V106A/M and Y181C DRMs. 2015 Journal of clinical virology Result HIV K103N;V106A;V106M;Y181C 20;101;101;113 25;108;108;118 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. K65R was detected at a low frequency in all patients. 2015 Journal of clinical virology Result HIV K65R 0 4 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. Two infants (13%) had DRMs to NNRTI, detected by bulk sequencing; one had K103N and the other - Y181I. 2015 Journal of clinical virology Result HIV K103N;Y181I 74;96 79;101 NNRTI 30 35 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. Above findings suggested that W427S immunization caused stronger T cell proliferation but the proliferation of splenocytes is associated inversely with Tfh amounts and serum IgG concentrations. 2014 PloS one Result HIV W427S 30 35 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. Accordingly, the wild-type gp120 immunized mice also displayed higher serum IgG concentrations than the W427S immunized mice (P = 0.0132). 2014 PloS one Result HIV W427S 104 109 gp120 27 32 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. And, a slightly higher proliferation in W427S group compared with that in the wide-type group was also observed (P = 0.2262). 2014 PloS one Result HIV W427S 40 45 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. And, both wild-type and W427S groups showed higher serum IgG levels than the adjuvant control (P<0.001 and P = 0.0135). 2014 PloS one Result HIV W427S 24 29 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. For the homologues HIV-1 06044 gp120 protein binding, the mutant W427S gp120 elicited significantly higher specific antibody titers compared with the wild-type gp120 at dilution 1:100 (P = 0.0481) and 1:1000 (P = 0.0267). 2014 PloS one Result HIV W427S 65 70 gp120;gp120;gp120 31;71;160 36;76;165 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. Furthermore, the concentrations of IL-21 in the splenocyte culture supernatants in the wild-type gp120 immunized mice were higher than those in W427S group and PBS group though no statistically significance was observed. 2014 PloS one Result HIV W427S 144 149 gp120 97 102 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. However, the W427S gp120 immunization induced higher number of memory Tfh cells compared with wild-type gp120 immunization (P = 0.0331) (em Tfh cells P = 0.0194 and cm Tfh cells P = 0.1791). 2014 PloS one Result HIV W427S 13 18 gp120;gp120 19;104 24;109 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. However, the wild-type gp120 did not induce higher specific ASC in BM compared with W427S. 2014 PloS one Result HIV W427S 84 89 gp120 23 28 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. Moreover, the frequency of the memory CD4+ T cells in all splenocytes of W427S gp120 immunized mice was also higher than that from wide-type gp120 immunized mice though no statistically significance was observed (S1 and S2 Figs.). 2014 PloS one Result HIV W427S 73 78 gp120;gp120 79;141 84;146 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. On contrary, W427S gp120 elicited neutralizing antibodies in 2 of 4 animals (neutralization percentages were equal or higher than 50%) against either 06044 or SF162. 2014 PloS one Result HIV W427S 13 18 gp120 19 24 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. Since there was a stronger specific splenocyte proliferation and Ab response in the W427S gp120 immunized mice, we further assessed the memory T cells to explore the association of recall responses and the specific Ab production. 2014 PloS one Result HIV W427S 84 89 gp120 90 95 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. The endpoint titers of the specific binding Abs from the W427S and wild-type gp120 immunized mice were 3.87 and 3.64 to HIV-1 Bal gp120 protein, and 4.65 and 4.81 to HIV-1 06044 wild-type gp120 protein (reciprocal log10 dilution), respectively. 2014 PloS one Result HIV W427S 57 62 gp120;gp120;gp120 77;130;188 82;135;193 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. These results indicated that the W427S induced not only higher specific binding antibodies, but also the neutralizing activity. 2014 PloS one Result HIV W427S 33 38 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. We found a significant increase of the Tfh frequency in the all splenocytes after the immunization with the wild-type gp120 compared with the W427S gp120 (P = 0.0822). 2014 PloS one Result HIV W427S 142 147 gp120;gp120 118;148 123;153 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. We found a slightly higher frequency of total IgG ASCs in the wild-type gp120 immunized mice than that in W427S group, though no statistically significance was observed. 2014 PloS one Result HIV W427S 106 111 gp120 72 77 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. We found that the mutant W427S gp120 elicited higher specific antibody titers against HIV-1 Bal gp120 compared with the wild-type gp120 though there is no statistically significance. 2014 PloS one Result HIV W427S 25 30 gp120;gp120;gp120 31;96;130 36;101;135 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. We next thought if the higher ability of specific Ab induction by the W427S immunization was attributed to a stronger T cell proliferation against the specific epitopes. 2014 PloS one Result HIV W427S 70 75 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. 3.3 Comparison of the pre-steady state kinetic parameters of wild type and Y115F HIV-1 RT proteins. 2015 Antiviral research Result HIV Y115F 75 80 RT 87 89 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. 3.4 3'dCTP chain terminator incorporation by wild type and Y115F HIV-1 RT proteins. 2015 Antiviral research Result HIV Y115F 59 64 RT 71 73 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. 3'dCTP) of these two proteins demonstrates that the Y115F RT enzyme discriminates against 3'dCTP 12-fold less effectively than wild type RT. 2015 Antiviral research Result HIV Y115F 52 57 RT;RT 58;137 60;139 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. As such, we determined the pre-steady state kinetic values of wild type HIV-1 and Y115F RT enzymes with 3'dCTP. 2015 Antiviral research Result HIV Y115F 82 87 RT 88 90 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. Collectively, our data support that an alteration in the residue Y115 to Y115F allows non-canonical CTP easier access to the substrate-binding pocket of Y115F HIV-1 RT. 2015 Antiviral research Result HIV Y115F;Y115F 73;153 78;158 RT 165 167 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. From Table 3, the pre-steady state kinetic values of Y115F RT display little differences in Kd and kpol values during the canonical dCTP incorporation, resulting in nearly equal overall dCTP incorporation efficiency when compared with WT RT. 2015 Antiviral research Result HIV Y115F 53 58 RT;RT 59;238 61;240 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. However, when the Kd and the kpol values were measured with non-canonical CTP, the Y115F mutant showed an equal kpol value and a 13-fold lower Kd as compared to wild type RT. 2015 Antiviral research Result HIV Y115F 83 88 RT 171 173 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. Selectivity between Y115F and WT RT for CTP was the highest, and not surprisingly, the lowest selectivity was for dCTP. 2015 Antiviral research Result HIV Y115F 20 25 RT 33 35 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. The higher catalytic efficiency of Y115F RT for 3'dCTP incorporation is due to a 6-fold tighter binding affinity to the substrate compared to wild type RT. 2015 Antiviral research Result HIV Y115F 35 40 RT;RT 41;152 43;154 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. The Y115F RT enzyme displayed a 12-fold higher catalytic efficiency for 3'dCTP incorporation than WT RT. 2015 Antiviral research Result HIV Y115F 4 9 RT;RT 10;101 12;103 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. These data demonstrate that the Y115F RT efficiently incorporates non-canonical CTP by exclusively increasing its binding affinity to CTP. 2015 Antiviral research Result HIV Y115F 32 37 RT 38 40 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. We purified Y115F RT with 40% active concentrations which displayed a biphasic burst of product formation suggesting that the mechanistic pathway was not changed by the mutant RT (Data not shown). 2015 Antiviral research Result HIV Y115F 12 17 RT;RT 18;176 20;178 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. We suspect that the hydroxyl group in Y115 may clash with 2'-OH group of an incoming CTP leading to the 13-fold difference we see in binding affinity for WT versus Y115F RT. 2015 Antiviral research Result HIV Y115F 164 169 RT 170 172 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. With this in mind, we determined the pre-steady state Kd and kpol values of Y115F HIV-1 RT for dCTP and CTP. 2015 Antiviral research Result HIV Y115F 76 81 RT 88 90 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. Y115A, Y115V) reduce RT's ability to gate the active site and to exclude rNTP incorporation. 2015 Antiviral research Result HIV Y115V;Y115A 7;0 12;5 RT 21 23 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. Y115F RT's selectivity for dCTP over CTP was 1714 +- 297.4, which suggests that WT RT has a 10-fold higher selectivity for dCTP over CTP when compared with Y115F RT. 2015 Antiviral research Result HIV Y115F;Y115F 156;0 161;5 RT;RT;RT 6;83;162 8;85;164 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. 26.44 kcal/mol); while for the mutant V32I the DeltaH is even favorable than that of WT (-42.15 vs. 2015 Journal of molecular graphics & modelling Result HIV V32I 38 42 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. According to Tables 1 and 2, the binding Gibbs free energies for the binding of TMC114 with two mutants V32I and M46L at two sites (2T) are closer to the experimental results than those binding at only active site (1T). 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 113;104 117;108 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. According to TGBTOT in Table S2 and Figure 10, the V32I mutant directly increases the binding affinity by approximately -0.19 (Val32 to Ile32) and -1.05 (Val32' to Ile32') kcal/mol, which only accounts for 2.11% of the DeltaGtotal. 2015 Journal of molecular graphics & modelling Result HIV V32I;V32I 127;51 141;55 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. According to the RMSD average values of the three complexes, V32I-2T complex has a higher mean (1.12 A) than the WT (1.01 A) and M46L-2T mutant (0.96 A), with a respective standard deviation (SD) of 0.21, 0.16 and 0. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 129;61 133;65 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Additionally, in order to differentiate the impact of TMC114 binding on chain-B from that of ligand free chain-A, we computed the individual RMSD for the chains of each complexes and shown in the Figure S13B and S13C. 2015 Journal of molecular graphics & modelling Result HIV S13C 212 216 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Analyzing the frequency distribution plot for the TriCa angle G48-G49-I50 (Figure 8c), it was found that the distribution of the angle for WT-1T and M46L-2T overlaps substantially; however, the V32I-2T distribution shows a difference as compared to the other two. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 149;194 153;198 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. As compared with the binding components for 1T complexes in Table 2, the binding of the second ligand on the flap region considerably enhances the electrostatic as well as van der Waal's contributions in V32I-2T and M46L-2T. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 216;204 220;208 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. As shown in the figure and table, the calculated binding free energies of WT-1T, V32I-2T and M46L-2T complexes are -14.67, -11.25 and -10.78 kcal/mol, respectively, suggesting that the binding free energy of WT is higher than the V32I and M46L mutants. 2015 Journal of molecular graphics & modelling Result HIV M46L;M46L;V32I;V32I 93;239;81;230 97;243;85;234 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Contributions of the binding free energies of complexes WT-1T, V32I-2T and M46L-2T are summarized in Table 1 and Figure 9. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 75;63 79;67 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Figure S3 shows the time-series distance plot between the flap tip residues (Ile50 - Ile50') for the three systems (WT-1T, V32I-1T, and the M46L-1T/TMC114 complexes), which have almost overlapped distances with average values of 5.92 A, 5.82 A, and 5.91 A, respectively. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 140;123 144;127 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. For flap-A, the RMSDs for all the three complexes seems to be overlapped and ranges from 0.2 to 1.2 A with average values of 0.45 A, 0.70 A and 0.58 A for WT-1T, V32I-2T and M46L-2T, respectively. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 174;162 178;166 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. For M46L-2T, van der Waals effect dominates over the (Ele + GB) from residues Trp42', Lys55' and Arg57' towards the contribution. 2015 Journal of molecular graphics & modelling Result HIV M46L 4 8 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. For the M46L-2T mutant, the distribution has one peak around 6.4 A, whereas for WT-1T and V32I-2T mutant, the peak locates around 5.8 A, region. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 8;90 12;94 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. For V32I-2T, the entropy contribution (-TDeltaS) reaches to 48.41 kcal/mol while as for V32I-1T it is only 27.85 kcal/mol. 2015 Journal of molecular graphics & modelling Result HIV V32I;V32I 4;88 8;92 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. From this study, it seems that for M46L-2T, the average flap tip to active site distances for both the chains is longer than WT-1T, making the active site volume little wider. 2015 Journal of molecular graphics & modelling Result HIV M46L 35 39 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Hence, the mean of the double bound M46L mutant structure is more (~0.5 A) than the WT and V32I, suggesting that there is a floppy movement of flaps in M46L-2T as compared to WT-1T and V32I-2T/HIV-1-pr structures and probably make the active site volume larger. 2015 Journal of molecular graphics & modelling Result HIV M46L;M46L;V32I;V32I 36;152;91;185 40;156;95;189 PR 199 201 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. However, apart from that, mutant V32I-2T has higher values from around 10ns onwards. 2015 Journal of molecular graphics & modelling Result HIV V32I 33 37 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. However, for chain-B, the distribution plots for WT-1T and V32I-2T shares the overlapping as compared to M46L-2T, which shows a wider values. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 105;59 109;63 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. However, for flap-B, where the inhibitor is bound, there is a difference in the RMSDs for the mutant M46L-2T from that of WT-1T and V32I-2T at around 3-4 ns. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 101;132 105;136 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. However, the entropy penalty eventually compress the binding Gibbs affinities (DeltaG = DeltaH - TDeltaS) and trigger the drug resistance for the V32I and M46L mutations. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 155;146 159;150 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. However, the mean for the flap-B RMSDs, doesn't differ amongst the mutants with 0.65 A for V32I-2T and 0.64 A for M46L-2T. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 114;91 118;95 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. In general for all proteases (WT, V32I and M46L) the average flap tip-active site distance in chain-B is longer than that of chain-A. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 43;34 47;38 PR 19 28 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. In order to get insights to the different contributions of binding free energy for double bound TMC114 with WT, V32I and M46L mutant, binding free energies were calculated for all the complexes using the MM-PBSA method. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 121;112 125;116 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. It is clearly seen that, at around 4 ns the flap tips distance rises up to 8.60 A in case of M46L-2T mutant. 2015 Journal of molecular graphics & modelling Result HIV M46L 93 97 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. It was also observed that, for V32I-2T, binding of the TMC-flap is mainly due to the van der Waals effect of Arg57' and Lys55', but the sum of electrostatic interactions and polar solvation energy (Ele + GB), from Arg57' is the highest unfavorable contribution as shown in Figure S14 and Table S2. 2015 Journal of molecular graphics & modelling Result HIV V32I 31 35 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. It was observed that, with binding of the TMC114 (TMC-flap) at the flap region simultaneously with that of TMC114 (TMC-AS) bound at the active site of both the mutants (V32I-2T and M46L-2T), the overall binding energies from the contributing residues are increased (Figure S14). 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 181;169 185;173 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Looking at the time-series plot for the TriCa angle in Figure 8a, we observed that the angles are seems to be overlapped for all the complexes except for around 10 ns where the M46L-2T has visibly lower angular values and around 15-17 ns where V32I-2T has lower values. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 177;244 181;248 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Moreover, for the whole protein the average residual atomic fluctuation also seems to be higher in case of V32I mutant (1.00A) than WT (0.91 A) and M46L (0.92 A). 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 148;107 152;111 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Overall, the calculated data is consistent with the sequence of the experimental affinity of WT (-15.20 kcal/mol), V32I and M46L (-11.6 and -11.3 kcal/mol) complexes. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 124;115 128;119 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Residues like Pro44', Lys55', Arg57' are primarily involved for the interaction in V32I-2T structures, and Trp42', Pro44', Lys55', Val56' and Arg57' are involved for the M46L-2T structures. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 170;83 174;87 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. RMSD values for the Calpha atoms of the single bound (WT-1T, V32I-1T and M46L-1T) HIV-1-pr/TMC114 complexes, looks more stable than double bound (2T) complexes, as shown in supplementary Figure S1. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 73;61 77;65 PR 88 90 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Similarly M46L-2T also has significantly higher unfavorable entropic contribution as compared to M46L-1T (45.63 kcal/mol vs. 2015 Journal of molecular graphics & modelling Result HIV M46L;M46L 10;97 14;101 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Table 2 shows that the DeltaH for the M46L mutant does not change much (-41.31 vs. 2015 Journal of molecular graphics & modelling Result HIV M46L 38 42 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Table S2 further shows that the M46L-2T mutant indirectly decreases the binding affinity by approximately 3.80 kcal/mol, of which approximately 59% of the total loss (by -2.25 kcal) comes from three residues Arg08', (-0.75); Asp25',(-0.82) and Glu35' (-0.68) kcal/mol, which is accompanied by a substantial increase in interaction from the residues like Gly27, Ala28, Asp29, Trp42'-Lys43'-Pro44', Ile47', Lys55'-Val56'-Arg57'. 2015 Journal of molecular graphics & modelling Result HIV M46L 32 36 Asp;Asp 225;368 228;371 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Taking example of Ile32' in the V32I-2T mutant, we found that the mutated residue (Val32' to Ile32') in chain-B has substantial contribution (-1.72 kcal/mol) to the DeltaGtotal, but not from the residue (Ile32) in chain-A. 2015 Journal of molecular graphics & modelling Result HIV V32I 32 36 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The affinity of the mutation V32I-1T complex decreases by 2.24kcal/mol, and that of the M46L-1T decreases by 3.55 kcal/mol with respect to the WT-1T complex. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 88;29 92;33 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The average flap RMSD of M46L (0.58 A) mutant was found to be little less than WT (0.73 A) and V32I (0.71 A) with respective SD of 0.12, 0.12 and 0.13 A. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 25;95 29;99 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The average RMSF values per-residue in the flap and active-site binding region for the WT-1T, V32I-2T and M46L-2T HIV-1-pr/TMC114 complexes are 0.89, 1.07 and 0.98 A, respectively. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 106;94 110;98 PR 120 122 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The binding affinities (DeltaG) of V32I-2T and M46L-2T complexes decrease by 3.42 and 3.89 kcal/mol with respect to the WT-1T complex, which suggests that both the mutants demonstrate drug resistance to TMC114 heavily. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 47;35 51;39 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The calculated binding free energies (DeltaG) of WT-1T, V32I-1T and M46L-1T complexes are -14.67, -12.43 and -11.12 kcal/mol respectively. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 68;56 72;60 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The difference between the distances in double bound (2T) complex from that of single bound (1T) complex is that, the difference in average distance of chain-B in M46L-2T mutant by about 0.61 A making the active site volume little wider than the WT-1T. 2015 Journal of molecular graphics & modelling Result HIV M46L 163 167 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The difference between the double bound V32I-2T and M46L-2T/HIV-1-pr was found to be broader than that of the single bound V32I-1T and M46L-1T/HIV-1-pr mutants (Figure 7a). 2015 Journal of molecular graphics & modelling Result HIV M46L;M46L;V32I;V32I 52;135;40;123 56;139;44;127 PR;PR 66;149 68;151 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The difference in the flap tips distances for the 1T and 2T complexes remains mostly in case of M46L mutant, where the distance is ~0.5 A higher in 2T than 1T, suggesting that the higher mobility of the flaps in 2T, even if an extra TMC114 bound on one of the flaps. 2015 Journal of molecular graphics & modelling Result HIV M46L 96 100 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The distance between the flap tips (Ile50Calpha and Ile50'Calpha) and the catalytic aspartates (Asp25Calpha and Asp25'Calpha) for WT-1T, V32I-1T and M46L-1T HIV-1-pr/TMC114 shows that the distances in chain-A for all the three complexes are almost overlapped throughout the simulation with an average distance of 13.89, 14.05 and 14.05 A, respectively, which are slightly shorter than those of double binding for the two mutants. 2015 Journal of molecular graphics & modelling Result HIV D25A;D25C;D25L;I50A;I50C;I50L;M46L;V32I 96;96;96;36;36;36;149;137 105;105;105;45;45;45;153;141 Asp;PR 112;163 115;165 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The distance between the side-chains of residue Ile47 to the O26 atom of TMC114 suggest a smaller (3.4 A) one for WT-1T as compared to the mutants V32I-2T (4.7 A) and M46L-2T (5.6 A) (Figure 11a). 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 167;147 171;151 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The flap dynamics of the inhibitor bound proteases can be further analyzed by the TriCa (Gly49-Ile50-Gly51) Calpha angles in the flap tip region for all three WT-1T, V32I-2T and M46L-2T/HIV-1-pr complexes. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 178;166 182;170 PR;PR 41;192 50;194 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The frequency distribution plots (Figure 6c and 6d) for the flap tip-active site distances for chains A and B show the clear difference between WT-1T, V32I-2T and M46l-2T. 2015 Journal of molecular graphics & modelling Result HIV V32I 151 155 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The frequency distribution plots for flap tipA-flap tipB distance in Figure 7b also clearly show that with respect to (I50-I50') Calpha distance, WT-1T and V32I-2T mutant assemble different types of conformations as compared with the M46L-2T mutant. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 234;156 238;160 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The Ile50(Ile50') - Asp25(Asp25') distances for double bound TMC114 mutants (V32I-2T and M46L-2T) were calculated from the MD trajectories and the observed results were compared with those of WT-1T proteins. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 89;77 93;81 Asp;Asp 20;26 23;29 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mean and SD of the TriCa angles for the V32I-2T (M46L-2T) distribution are 100.07 (99.22) and 7.02 (5.05), respectively, whereas for the WT-1T, the mean and SD are 103.97 and 9.79 . 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 53;44 57;48 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mean distance of the distribution for the mutant M46L differs by approximately 0.51 A from WT and V32I. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 53;102 57;106 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mean distances (SD) are 5.92 A (0.20 A) for WT-1T and 5.85 A (0.20 A) for V32I-2T, and 6.39 A (0.38 A) for M46L-2T mutant, respectively. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 111;78 115;82 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mean distances and SD of WT-1T (V32I-2T) are 14.99 (15.00) A and 0.33 (0.47) A, respectively; while for the M46L-2T, the mean and SD are 15.51 A and 0.41 A, respectively. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 112;36 116;40 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mean distances of flap tip-active site residues in chain A are 13.89, 14.25 and 14.19 A with SD values of 0.29, 0.34, and 0.33 A for WT-1T, V32I-2T and M46L-2T-HIV-1-pr/TMC114, respectively. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 156;144 160;148 PR 170 172 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mean values of the TriCa angle for WT-1T (M46L-2T) trajectories are 140.31 (137.89 ) and SD is 5.81 (7.94 ), whereas for the V32I-2T the mean and SD are 143.13 and 5.32 . 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 46;131 50;135 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mean values of WT-1T and M46L-2T are smaller than that of V32I-2T complex by ~3 and > 5 , which implies the more curling in of the flap tips in WT-1T and M46L-2T than the V32I-2T. 2015 Journal of molecular graphics & modelling Result HIV M46L;M46L;V32I;V32I 29;159;62;176 33;163;66;180 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mutation M46L leads to the decrease in binding contributions from one of the flap residues Ile47 also probably due to the loss in van der Waal's contact between the residue and inhibitor. 2015 Journal of molecular graphics & modelling Result HIV M46L 13 17 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mutation M46L-2T has little direct contributions to the binding affinity of TMC114 with HIV-1-pr in the current study. 2015 Journal of molecular graphics & modelling Result HIV M46L 13 17 PR 98 100 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mutation V32I leads to the decrease in binding contributions from four of the active-site residues Leu23 (-0.19 vs -0.85 kcal/mol); Gly27' (-0.23 vs -0.76 kcal/mol); Ala28' (-1.26 vs -2.22 kcal/mol ); and Asp29' (-0.34 vs -1.17 kcal/mol for WT) and one active-site wall residue Ile84 (-1.29 vs -1.95 kcal/mol) in total about 3.64 kcal/mol, which is approximately 6.19% of the DeltaGtotal and approximate 37% of the total loss. 2015 Journal of molecular graphics & modelling Result HIV V32I 13 17 Asp 209 212 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mutation V32I-2T has moderate direct contributions to the binding affinity of TMC114 with HIV-1-pr. 2015 Journal of molecular graphics & modelling Result HIV V32I 13 17 PR 100 102 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The RMSD of the flap residues (43-58 and 43'-58') in both the chains-A and B in the double bound complexes (V32I-2T and M46L-2T) and compared to the RMSD of the WT-1T flaps was illustrated in Figure S13. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 120;108 124;112 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The RMSD plots indicate that the conformations of the WT-1T, V32I-1T and M46L-1T mutant HIV-pr/TMC114 complexes are in good equilibrium. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 73;61 77;65 PR 92 94 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The RMSD plots indicate that the conformations of the WT-1T, V32I-2T and M46L-2T mutant HIV-1-pr/TMC114 complexes are in good equilibrium. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 73;61 77;65 PR 94 96 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The time series plot (Figure 8b) also shows the higher fluctuations of WT-1T and V32I-2T structures as compared to M46L-2T structures. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 115;81 119;85 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The trajectory again continues parallel to the mutant M46L-2T. 2015 Journal of molecular graphics & modelling Result HIV M46L 54 58 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Therefore, the mean of the two distributions of V32I-2T and M46L-2T differ by 4 and 5 from that of the WT-1T. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 60;48 64;52 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. Thus, the present all-atom molecular dynamics simulation results provide a theoretical evidence for the binding of TMC114 with V32I and M46L-HIV-1-pr at both active and flap sites. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 136;127 140;131 PR 147 149 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. V32I mutant complex again has a slightly higher mean (1.14 A) than the WT (1.00 A) and M46L mutant (1.03 A). 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 87;0 91;4 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. While considerable overlaps exist in the WT-1T and V32I-2T trajectories, the distance between the flap tips was recognized to fluctuate more in the case of M46L than in the WT and mutant V32I. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I;V32I 156;51;187 160;55;191 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. While significant overlaps exist in the three distributions, the distance between the flap tips was recognized to fluctuate more in the case of M46L-2T and it covers wider values as compared to WT-1T and V32I-2T HIV-1-pr mutant. 2015 Journal of molecular graphics & modelling Result HIV M46L;V32I 144;204 148;208 PR 218 220 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Again, the M36I form was more mobile along the high amplitude motions described by the first PCs. 2014 BMC genomics Result HIV M36I 11 15 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. As displayed in Figure 3A this analysis shows that independently of the M36I polymorphism, PR stayed in the same cluster during the whole time-trajectory for all systems, except for the WT-PR - RH-IN system. 2014 BMC genomics Result HIV M36I 72 76 IN;PR;PR 197;91;189 199;93;191 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. By contrast, after oscillations during the first 10 ns, the M36I form reached a close region of the conformational space and remained there until the end of the simulation. 2014 BMC genomics Result HIV M36I 60 64 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. By contrast, RH-IN substrate, is the only one for which we clearly see an increased binding to M36I PR (DeltaDeltaGb = 4.9 Kcal/mol). 2014 BMC genomics Result HIV M36I 95 99 IN;PR 16;100 18;102 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Comparing the extent of sampling in WT and M36I forms. 2014 BMC genomics Result HIV M36I 43 47 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. For RH-IN, by contrast, binding appeared more stable with M36I-RT. 2014 BMC genomics Result HIV M36I 58 62 IN;RT 7;63 9;65 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. For the other substrates, this effect is not observed with the M36I substitution. 2014 BMC genomics Result HIV M36I 63 67 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. For the RT-RH substrate, M36I substitution did not change the binding affinity (DeltaDeltaGb = 0.6 Kcal/mol). 2014 BMC genomics Result HIV M36I 25 29 RT 8 10 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. From the six crystallographic structures of B-subtype PR complexed with different substrate (Table 1) available in the PDB (1F7A, and 1KJ4, 1KJ7, 1KJF, 1KJG, 1KJH), we performed comparative modeling in order to built the M36I PR complexes, using each structure independently as template (as previously described and Methods). 2014 BMC genomics Result HIV M36I 221 225 PR;PR 54;226 56;228 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. However, according to our RMSF analysis, we only observed such a stabilization of the flap hinge on the mutant M36I-PR when it is bound to RH-IN. 2014 BMC genomics Result HIV M36I 111 115 IN;PR 142;116 144;118 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. However, it is not shown yet that the modulation of the binding affinities is due to the differences in the dynamical behavior of the WT and M36I forms. 2014 BMC genomics Result HIV M36I 141 145 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. In addition, the mean contact area with this substrate was higher in the M36I form, which explains the increase in DeltaGsol/np. 2014 BMC genomics Result HIV M36I 73 77 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. In general, the M36I-complexes presented lower affinity than the WT for the majority of substrates, yielding negative values for DeltaDeltaGb. 2014 BMC genomics Result HIV M36I 16 20 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. In the latter, as opposed to the M36I - RH-IN system, which was stable, we clearly observed after 6 ns a shift towards a distinct PR conformation, which remained stable until the end of the 50 ns period. 2014 BMC genomics Result HIV M36I 33 37 IN;PR 43;130 45;132 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Interestingly, after inspection of the flap hinge region, which comprises residues 34-40, for the RH-IN complexes, we noticed higher fluctuations in the WT compared to the M36I-PR; while other regions presented a similar behavior (Additional file 3). 2014 BMC genomics Result HIV M36I 172 176 IN;PR 101;177 103;179 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Interestingly, the projection of the WT trajectories revealed a smaller extent of sampling as compared to their respective counterparts from the M36I trajectories (Additional file 7). 2014 BMC genomics Result HIV M36I 145 149 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. M36I-CA-P2) for the first two components only. 2014 BMC genomics Result HIV M36I 0 4 Capsid 5 7 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. MA-CA: Table 2 revealed stronger van der Waals interactions in the WT enzyme, which probably result from the higher stability of this form as compared with the M36I PR. 2014 BMC genomics Result HIV M36I 160 164 Matrix;Capsid;PR 0;3;165 2;5;167 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Meanwhile, the CA-p2, p1-p6 substrates were more stable when bound to WT PR, since we observed the occurrence of a structural transition in each M36I system: around 3 ns and 35 ns, respectively. 2014 BMC genomics Result HIV M36I 145 149 Gag;Capsid;PR 25;15;73 27;17;75 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Ode et al suggested that the role of M36I mutation was to reduce the volume of the binding cavity in the inhibitor-bound state. 2014 BMC genomics Result HIV M36I 37 41 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. p1-p6: Similarly to the MA-CA complexes, the M36I PR presented more mobility along its two first principal components (Additional file 7), which may be related to the decrease in van der Waals contributions (Table 2). 2014 BMC genomics Result HIV M36I 45 49 Gag;Matrix;Capsid;PR 3;24;27;50 5;26;29;52 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Remarkably, the only exception was the RH-IN complexes (Figure 6A), in which the M36I form explored a smaller region than the WT one. 2014 BMC genomics Result HIV M36I 81 85 IN 42 44 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Subsequently, solvation, ions insertion, energy minimization and consecutive MD simulations (heating, equilibration and production) were conducted for the 12 systems (6 for the B-subtype and 6 for the M36I). 2014 BMC genomics Result HIV M36I 201 205 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. The flap region (around the Ile 50 and 149) was more flexible for some M36I PR (MA-CA, p1-p6 and p2-NC). 2014 BMC genomics Result HIV M36I 71 75 NC;Gag;Matrix;Capsid;PR 100;90;80;83;76 102;92;82;85;78 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. The terminal groups were less stable for the M36I-complexed substrates (with the exception of the RH-IN). 2014 BMC genomics Result HIV M36I 45 49 IN 101 103 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. These results are indeed interesting since they demonstrate that despite the similar stable behaviors revealed by RMSD analysis, PCA projection can differentiate the WT and M36I forms in terms of the stabilization of large amplitude motions. 2014 BMC genomics Result HIV M36I 173 177 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. This analysis allowed us to distinguish two different populations in the PR-WT contrasting with the narrower normal distribution for the M36I PR. 2014 BMC genomics Result HIV M36I 137 141 PR;PR 73;142 75;144 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. This was expected since the behaviors of the WT and M36I forms bound to the same substrate were similar (Figure 3 and Additional file 2). 2014 BMC genomics Result HIV M36I 52 56 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. We also conducted the same analysis for the other simulated systems and observed a single-population distribution, independently of the presence of the M36I substitution (Additional file 2). 2014 BMC genomics Result HIV M36I 152 156 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. We observed similar profiles for each substrate bound to WT or M36I PR. 2014 BMC genomics Result HIV M36I 63 67 PR 68 70 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. We obtained frequencies below 10% for most of the substrates, except for: RT-RH (23.49% consB / 29% M36I) and MA-CA when bound to the mutant enzyme (29.78 %). 2014 BMC genomics Result HIV M36I 100 104 Matrix;Capsid;RT 110;113;74 112;115;76 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. All mutations caused a decrease in RC as compared to HIV-WT, except for mutation L90M in protease. 2014 Retrovirology Result HIV L90M 81 85 PR 89 97 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. For M41L, it has been described that V60I and S162A function as compensatory mutations in transmitted HIV-1 variants. 2014 Retrovirology Result HIV M41L;S162A;V60I 4;46;37 8;51;41 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. However, in vivo the variant containing this M41L mutation persisted for 8 months without selection of V60I or S162A before the patient initiated therapy (data not shown). 2014 Retrovirology Result HIV M41L;S162A;V60I 45;111;103 49;116;107 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In addition, two more complex transmitted viruses were studied: a protease-variant containing I54V + V82A + L90M and an RT-variant carrying M41L + T69S + L210E + T215S. 2014 Retrovirology Result HIV I54V;L210E;L90M;M41L;T215S;T69S;V82A 94;154;108;140;162;147;101 98;159;112;144;167;151;105 PR;RT 66;120 74;122 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In line with these results, the RC of pK103N and pM41L + T69S + L210E + T215S surpassed the RC of the corresponding SDM-viruses to the level of wild type virus. 2014 Retrovirology Result HIV L210E;T215S;T69S 64;72;57 69;77;61 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In this genetic background, the viral RC was as low as HIV-M184T and even lower than SDM-M41L. 2014 Retrovirology Result HIV M184T;M41L 59;89 64;93 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. M46I and M46L in protease resulted in the most severe reduction of RC (Figure 1). 2014 Retrovirology Result HIV M46L;M46I 9;0 13;4 PR 17 25 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Site-directed mutants HIV-M184V, -I and -T with a known impact on RC were used as controls, and to enable comparison of RC between various experiments. 2014 Retrovirology Result HIV M184V 26 31 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. The difference in RC between HIV-WT, -M184V and -M184I has been demonstrated to be biologically relevant in vivo. 2014 Retrovirology Result HIV M184I;M184V 49;38 54;43 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. The RC of all protease mutation-harboring patient-derived viruses was higher than the corresponding SDM-viruses, and the RC of pL90M and pI54V + V82A + L90M were even higher than WT. 2014 Retrovirology Result HIV L90M;V82A 152;145 156;149 PR;PI 14;137 22;139 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. The RC of p46I and p46L was similar to controls HIV-M184I and -V, indicating a diminished replication. 2014 Retrovirology Result HIV M184I 52 57 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. The reduction in RC of the M41L, M41L + T215Y and K103N variants was comparable to each other, and to controls HIV-M184V and -I. 2014 Retrovirology Result HIV K103N;M184V;M41L;M41L;T215Y 50;115;27;33;40 55;120;31;37;45 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. We constructed recombinant viruses using patient-derived protease containing M46L, M46I or L90M, or patient-derived n-terminus of RT containing M41L or K103N into HXB2. 2014 Retrovirology Result HIV K103N;L90M;M41L;M46I;M46L 152;91;144;83;77 157;95;148;87;81 PR;RT 57;130 65;132 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. We determined the impact of TDRM on viral RC by introducing frequently observed drug-resistance mutations M46I, M46L or L90M in protease or M41L, M41L + T215Y or K103N in RT in the background of the lab strain HXB2 by site-directed mutagenesis (Figure 1). 2014 Retrovirology Result HIV K103N;L90M;M41L;M41L;M46I;M46L;T215Y 162;120;140;146;106;112;153 167;124;144;150;110;116;158 PR;RT 128;171 136;173 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. We selected a patient-virus with M41L but without the potential compensatory mutations (pM41L). 2014 Retrovirology Result HIV M41L 33 37 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Among all the mutations detected, T74S (54.5%) in PR and E138A (17%), V179I (16%), followed by V118I and V179E (14% each) in RT were the most prevalent, while T69NS, V90I, and V106I were present at only 5% each. 2015 AIDS research and human retroviruses Result HIV E138A;T69N;T69S;T74S;V106I;V118I;V179E;V179I;V90I 57;159;159;34;176;95;105;70;166 62;164;164;38;181;100;110;75;170 PR;RT 50;125 52;127 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Due to the M41L mutation detected in one specimen, the virus would have reduced susceptibility to zidovudine (AZT) and stavudine (d4T). 2015 AIDS research and human retroviruses Result HIV M41L 11 15 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. E35K occurred in 5% of CRF02-AG but was absent in the rest of the other subtypes. 2015 AIDS research and human retroviruses Result HIV E35K 0 4 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Five specimens had A98G, K101EK, V108IV, K103N, E138A, and G190A occurring alone or in combination with each other, which could cause intermediate and/or high-level resistance to delavirdine (DLV), efavirenz (EFV), etravirine (ETR), and nevirapine (NVP). 2015 AIDS research and human retroviruses Result HIV A98G;E138A;G190A;K101E;K101K;K103N;V108I;V108V 19;48;59;25;25;41;33;33 23;53;64;31;31;46;39;39 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. For example, the E35Q mutation occurred in 67% of all subtype G sequences and in only 5% of CRF02-AG sequences, but was absent in all other subtypes and CRFs. 2015 AIDS research and human retroviruses Result HIV E35Q 17 21 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. In the PR region, one sample displayed the K43T mutation; another one had the M46L, while a third specimen had K53Y, A71V, and I85V. 2015 AIDS research and human retroviruses Result HIV A71V;I85V;K43T;K53Y;M46L 117;127;43;111;78 121;131;47;115;82 PR 7 9 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. L89T/I, the nonpolymorphic PI-selected mutation of uncertain phenotypic and clinical significance was also detected. 2015 AIDS research and human retroviruses Result HIV L89I;L89T 0;0 6;6 PI 27 29 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Of the 271 sequences analyzed, 11 polymorphic mutations (G16E, K20I, L23P, E35D, M36I, N37D/S/T, R57K, L63P, and V82I) in the PR and 3 (D123N and I135T/V) in the RT were identified. 2015 AIDS research and human retroviruses Result HIV D123N;E35D;G16E;I135T;I135V;K20I;L23P;L63P;M36I;N37D;N37S;N37T;R57K;V82I 136;75;57;146;146;63;69;103;81;87;87;87;97;113 142;79;61;153;153;67;73;107;85;95;95;95;101;117 PR;RT 126;162 128;164 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. The CPR analysis identified the PI mutations M46L, I85V, and F53Y as well as the NRTI mutations M41L and V75M, and the NNRTI mutations K101E, K103N, and G190A as Surveillance Drug Resistance Mutations (SDRM). 2015 AIDS research and human retroviruses Result HIV F53Y;G190A;I85V;K101E;K103N;M41L;M46L;V75M 61;153;51;135;142;96;45;105 65;158;55;140;147;100;49;109 NNRTI;NRTI;PI 119;81;32 124;85;34 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. The mutation E138A associated with a decreased response to ETR, the second generation NNRTI, was found in 16% (12/76) of the specimens displaying DR mutations. 2015 AIDS research and human retroviruses Result HIV E138A 13 18 NNRTI 86 91 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. The prevalence for T69NS, V90I, and V106I was 1.5%, respectively. 2015 AIDS research and human retroviruses Result HIV T69N;T69S;V106I;V90I 19;19;36;26 24;24;41;30 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. The T74S mutation was found in the PR of six specimens. 2015 AIDS research and human retroviruses Result HIV T74S 4 8 PR 35 37 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. We also detected NRTI selected mutations M41L, E44D, T69ANS, V75M, and V118I, and NNRTI mutations V90I, A98G, K101EQ, K103NR, V106I, V108I, E138A, V179EI, and G190A (Table 3). 2015 AIDS research and human retroviruses Result HIV A98G;E138A;E44D;G190A;K101E;K101Q;K103N;K103R;M41L;T69A;T69N;T69S;V106I;V108I;V118I;V179E;V179I;V75M;V90I 104;140;47;159;110;110;118;118;41;53;53;53;126;133;71;147;147;61;98 108;145;51;164;116;116;124;124;45;59;59;59;131;138;76;153;153;65;102 NNRTI;NRTI 82;17 87;21 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. We found that at position 179 of the RT gene, all sequences of CRF06-cpx (6/6), subtype G (2/2), and CRF43-02G (2/2) harbored the V179E mutation, while all sequences of CRF36-cpx (1/1), A/CRF02-AG (2/2), CRF36-cpx/B (2/2), A/CRF15-01B (4/4), and CRF25-cpx (2/2) had the V179I mutation. 2015 AIDS research and human retroviruses Result HIV V179E;V179I 130;270 135;275 RT 37 39 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Within the cohort, the rate of these mutations was 2.2% for T74S, 4% for V118I and V179E each, 4.5% for V179I, and 5% for E138A. 2015 AIDS research and human retroviruses Result HIV E138A;T74S;V118I;V179E;V179I 122;60;73;83;104 127;64;78;88;109 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. 5B), exposure to Tat Cys22 did not alter DA uptake in Y88F-hDAT and K92M-hDAT compared to WT hDAT. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 68;54 72;58 Tat 17 20 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. 5B); however, no effect of Tat was observed in Y88F-hDAT (F(1, 12) = 1.1; p > 0.05) and K92M-hDAT (F(1, 12) = 1.4; p > 0.05), suggesting that mutation of either Tyr88 or Lys92 in hDAT attenuates Tat-induced reduction of hDAT function. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 88;47 92;51 Tat;Tat 27;195 30;198 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. 6D), a two-way ANOVA revealed significant main effects of mutation (F(3, 12) = 18.1; p<0.001), time (F(5, 60) = 389.5; p<0.001) and significant mutation x time interaction (F(15, 60) = 8.6; p<0.001) for Y470F-hDAT, Y470H-hDAT and Y470A-hDAT compared to WT hDAT. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F;Y470H 230;203;215 235;208;220 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As a result, the Y88F mutation would not expect to influence the function of hDAT. 2015 Journal of neuroimmune pharmacology Result HIV Y88F 17 21 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As a result, the Y88F or K92M mutation on hDAT would be expected to decrease the binding between hDAT and Tat. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 25;17 29;21 Tat 106 109 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As described in Figure 6A, two-way ANOVA on the specific [3H]DA uptake in WT and Y470F-hDAT and Y470A-hDAT revealed a significant main effect of mutation (F(2, 18) = 99; p < 0.001), zinc (F(1, 18) = 40; p < 0.001) and a significant mutation x zinc interaction (F(2, 18) = 8.9; p < 0.01). 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F 96;81 101;86 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As shown in Figure 3A, compared to WT hDAT (15.7 +- 0.9 pmol/min/105 cells), the Y470A-hDAT displayed a decrease in the Vmax values [1.2 +- 0.2 pmol/min/105 cells, t(6) = 23, p<0.001, unpaired Student's t test], whereas the Y470F-hDAT did not alter the Vmax and the Km values. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F 81;224 86;229 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As shown in Figure 3B, no difference in the ratio of surface DAT (biotinylated DAT) to total DAT between WT hDAT and Y470F-hDAT (biotinylated/total: WT, 0.93 +- 0.09; and Y470F, 0.96 +- 0.1; p >0.05, one-way ANOVA) was found. 2015 Journal of neuroimmune pharmacology Result HIV Y470F;Y470F 117;171 122;176 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As shown in Figure 6C, after preloading with 0.05 microM [3H]DA for 20 min at room temperature, CHO cells transfected with WT hDAT, Y470H-hDAT, Y470F-hDAT and Y470A-hDAT were washed and fractional DA efflux samples were collected at the indicated times. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F;Y470H 159;144;132 164;149;137 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As shown in Figure 7C, a two-way ANOVA on the basal efflux of [3H]DA in Y88F-hDAT and K92M-hDAT revealed significant main effects of mutation (F(2, 6) = 28.1; p<0.01), time (F(5, 30) = 156; p<0.001) and significant mutation x time interaction (F(10, 30) = 511; p<0.001). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 86;72 90;76 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As shown in Table 1 and Figure 4A, the Vmax values were decreased in K92M-hDAT (4.5 +- 1.7 pmol/min/105 cells, t(5) = 3.3, p<0.05, unpaired Student's t test) but not altered in Y88F-hDAT (14.8 +- 3.7 pmol/min/105 cells) compared to WT hDAT (15.7 +- 0.9 pmol/min/105 cells). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 69;177 73;181 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As shown in Table 1, the apparent affinity (IC50) for DA was significantly decreased Y88F-hDAT [2010 +- 60 nM, t(6) = 3.8, p<0.01, unpaired Student's t test] and K92M-hDAT (2868 +- 48 nM, t(6) = 3.8, p<0.05, unpaired Student's t test), respectively, compared to the WT hDAT (1730 +- 82 nM). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 162;85 166;89 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. As shown in Table 2, the Bmax values of [3H]WIN 35,428 binding were decreased in Y88F-hDAT (5.8 +- 0.9 pmol/105 cells, t(6) = 2.1, p<0.05, unpaired Student's t test) and K92M-hDAT (2.4 +- 0.4 pmol/105 cells, t(6) = 6.3, p<0.001, unpaired Student's t test) compared with WT hDAT (9.7 +- 1.6 pmol/105 cells). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 170;81 174;85 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Compared to WT hDAT, DA efflux levels were elevated in Y470H-hDAT and Y470A-hDAT at all-time points (ps < 0.05, Bonferroni t-test). 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470H 70;55 75;60 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Compared to WT hDAT, Y88F and K92M mutants did not alter the basal efflux of [3H]MPP+ at all-time points. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 30;21 34;25 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Hence, the K92M mutation would negatively impact the transporting kinetics of DA. 2015 Journal of neuroimmune pharmacology Result HIV K92M 11 15 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. However, the potencies of cocaine and GBR12909 for inhibiting [3H]DA uptake were ~4.0-fold greater in Y88F-hDAT and K92M-hDAT as compared with WT hDAT (unpaired Student's t test). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 116;102 120;106 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. However, the potencies of cocaine were increased in Y88F-hDAT (85 +- 60 nM, t(8) =5.8, p<0.001) but not in K92M-hDAT compared to WT hDAT (150 +- 8.6 nM). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 107;52 111;56 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. In addition, the potencies of WIN 35,428 for inhibiting [3H]DA uptake was not significantly altered in Y88F-hDAT (20 +- 2 nM) but more potent in K92M-hDAT [10 +- 1.0 nM, t(6) = 5.0, p<0.01, unpaired Student's t test] compared to WT hDAT (39 +- 10 nM). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 145;103 149;107 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. In addition, two-way ANOVA on the specific [3H]WIN35,428 binding in WT and Y88F-hDAT and K92M-hDAT revealed a significant main effect of mutation (F(1, 18) = 5.3; p < 0.05), zinc (F(1, 18) = 5.1; p < 0.05); however, significant mutation x zinc interaction (F(2, 18) = 0.7; p > 0.05) was not significant. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 89;75 93;79 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. In contrast, as shown in Figure 6B, a two-way ANOVA on the specific [3H]WIN35,428 binding in WT and Y470F-hDAT and Y470A-hDAT revealed a significant main effect of mutation (F(2, 18) = 73; p < 0.001), zinc (F(1, 18) = 10.1; p < 0.01); however, no significant mutation x zinc interaction (F(2, 18) = 1.8; p > 0.05) was observed. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F 115;100 120;105 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. No difference in IC50 of GBR 12909 for inhibiting [3H]WIN 35,428 binding was found among Y88F-hDAT, K92M-hDAT and WT hDAT. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 100;89 104;93 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. On the basis of this principle, we recently reported that Y470H-hDAT exhibit an attenuation of Zn2+-mediated decreased [3H]DA uptake and increased [3H]WIN35,428 binding observed in WT hDAT, which demonstrates a preference for the inward-facing conformation of the transporter. 2015 Journal of neuroimmune pharmacology Result HIV Y470H 58 63 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. On the contrary, the Y470F mutation on hDAT would not affect the cation-pi interaction and, thus, should not significantly influent the binding affinity between hDAT and Tat. 2015 Journal of neuroimmune pharmacology Result HIV Y470F 21 26 Tat;PI 170;72 173;74 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Post-hoc analyses (unpaired Student's t test) revealed that the addition of Zn2+ increased [3H]WIN 35,428 binding in WT hDAT by 54% but did not significantly alter [3H]WIN 35,428 binding in Y88F-hDAT and K92M-hDAT, respectively, compared to their respective controls. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 204;190 208;194 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Post-hoc analyses showed that compared to WT hDAT, DA efflux levels were elevated at 1, 10, 20 min in Y470H-hDAT and at 1 and 10 min in Y470A-hDAT (ps < 0.05, Bonferroni t-test). 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470H 136;102 141;107 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Post-hoc analysis revealed that compared to WT hDAT, DA efflux levels were elevated at 1 and 10 min in K92M-hDAT (p < 0.05, Bonferroni t-test) but not in Y88F-hDAT. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 103;154 107;158 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Regarding to the potencies of DA, cocaine and GBR12909 for inhibiting [3H]WIN 35,428 binding (Table 2), the apparent affinity (IC50) for DA was decreased in Y88F-hDAT (2071 +- 340 nM, t(8) = 3.5, p<0.01) and K92M-hDAT (4211 +- 118 nM, t(8) = 2.7, p<0.05), respectively, compared to than the WT hDAT (827 +- 120 nM). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 208;157 212;161 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Similarly, as shown in Figure 4B, despite no differences in the ratio of surface DAT to total DAT between WT (1.0 +- 0.05), Y88F-hDAT (1.13 +- 0.13; p >0.05, one-way ANOVA) and K92M-hDAT (1.09 +- 0.09; p >0.05, one-way ANOVA), the absolute total DAT in K92M-hDAT was significantly decreased compared to WT hDAT (t(8) = 4.6, p<0.01, unpaired Student's t test). 2015 Journal of neuroimmune pharmacology Result HIV K92M;K92M;Y88F 177;253;124 181;257;128 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Tat (250 nM, final concentration) decreased the Vmax of [3H]DA uptake by 32% in WT hDAT (F(1, 8) = 23.6; p < 0.01) and by 47% in Y470F-hDAT (F(1, 8) = 15.4; p < 0.01), respectively; however, no effect of Tat was observed in Y470H-hDAT (p > 0.05) and Y470A-hDAT (p > 0.05), suggesting that the different substitutions at Tyr470 residue in hDAT differentially influence Tat-induced inhibition of DA uptake. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F;Y470H 250;129;224 255;134;229 Tat;Tat;Tat 0;204;368 3;207;371 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The addition of Zn2+ significantly decreased [3H]DA uptake in WT and Y88F-hDAT and K92M-hDAT by 48%, 73% and 81%, respectively (ps < 0.001 relative to control, unpaired Student's t test). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 83;69 87;73 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The addition of Zn2+ significantly decreased [3H]DA uptake in WT hDAT, Y470F-hDAT and Y470A-hDAT by 47%, 49% and 72%, respectively. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F 86;71 91;76 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The addition of Zn2+ significantly increased [3H]WIN 35,428 binding in WT hDAT by 48% (p< 0.05 relative to control, unpaired Student's t test) but not in Y470F-hDAT and Y470A-hDAT, indicating that Y470F and Y470A mutants attenuate Zn2+-induced increase in WIN 35,428 binding sites. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470A;Y470F;Y470F 169;207;154;197 174;212;159;202 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The immunoreactivity of total and surface DAT in Y470A-hDAT was undetectable (data not shown). 2015 Journal of neuroimmune pharmacology Result HIV Y470A 49 54 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The mutant-induced reduction of the Bmax values was accompanied by an increase in the Kd values in Y88F-hDAT (4.0 +- 0.6 nM, t(6) = 3.4, p<0.05, unpaired Student's t test) and K92M-hDAT (3.5 +- 1.1 nM, t(6) = 2.8, p<0.05, unpaired Student's t test) compared with WT hDAT 8.6 +- 1.1 nM). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 176;99 180;103 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. These computational insights are also consistent with the experimental data obtained for the K92M and Y88F mutants (see below). 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 93;102 97;106 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. These results suggest that Y88F and K92M mutants attenuate zinc modulation of [3H]WIN 35,428 binding sites but not [3H]DA uptake. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 36;27 40;31 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Thus, the decreased DA uptake in K92M-hDAT is not due to alteration of the available DAT on the cell surface. 2015 Journal of neuroimmune pharmacology Result HIV K92M 33 37 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Thus, the Y470H and Y470A mutation could decrease the Vmax of hDAT transporting function, whereas the Y470F mutation would not influence it. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F;Y470H 20;102;10 25;107;15 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. To determine whether these mutations of hDAT alter DAT surface expression, the immunoreactivity of total DAT and surface DAT in CHO cells transfected with WT or Y470F-hDAT, Y470A-hDAT, Y88F-hDAT or K92M-hDAT was examined using cell surface biotinylation followed by Western blotting. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y470A;Y470F;Y88F 198;173;161;185 202;178;166;189 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. To determine whether Y470F-hDAT and Y470A-hDAT show differential effects on Tat-induced decrease in DA uptake, we examined the specific [3H]DA uptake in WT hDAT and the Tyr470 mutants in the presence or absence of recombinant Tat1-86 or recombinant Tat Cys22. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F 36;21 41;26 Tat;Tat;Tat 76;226;249 79;229;252 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. To further determine whether other substitutions at tyrosine 470 residue show differential effects on the basal DA transport, two mutations at this residue (tyrosine to phenylalanine, Y470F and tyrosine to alanine, Y470A) were generated by site-directed mutagenesis. 2015 Journal of neuroimmune pharmacology Result HIV Y470A;Y470F 215;184 220;189 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Two mutations in hDAT (tyrosine to phenylalanine, Y88F-hDAT and lysine to methionine, K92M-hDAT) were generated by site-directed mutagenesis. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 86;50 90;54 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. We also determined the effects of Y88F-hDAT and K92M-hDAT on Tat-induced inhibition of DA uptake. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 48;34 52;38 Tat 61 64 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. We have demonstrated that mutation of tyrosine (Y470H) in hDAT displayed a decrease in the Vmax values of [3H]DA uptake under a control condition. 2015 Journal of neuroimmune pharmacology Result HIV Y470H 48 53 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. With regard to Y88F-hDAT and K92M-hDAT. 2015 Journal of neuroimmune pharmacology Result HIV K92M;Y88F 29;15 33;19 25653132 Epidemiological and molecular characteristics of HIV infection among money boys and general men who have sex with men in Shanghai, China. Both were of CRF01_AE subtype with PI-related major mutation, M46L, which confers resistance to nelfinavir (NFV) and other protease inhibitors. 2015 Infection, genetics and evolution Result HIV M46L 62 66 PR;PI 123;35 131;37 25653132 Epidemiological and molecular characteristics of HIV infection among money boys and general men who have sex with men in Shanghai, China. Several minor mutations were detected in the protease (PR) region of the pol gene: L10I (3.8%), V11I (1.9%), L33F (1.9%) and A71T/V (17.3%); and several others were detected in the reverse transcriptase (RT) region of the pol gene: T69A (1.9%), V118I (11.5%), L210M (1.9%), V179I (11.5%) and K101Q (1.9%). 2015 Infection, genetics and evolution Result HIV A71T;A71V;K101Q;L10I;L210M;L33F;T69A;V118I;V11I;V179I 125;125;292;83;260;109;232;245;96;274 131;131;297;87;265;113;236;250;100;279 RT;PR;Pol;Pol;PR;RT 181;45;73;222;55;204 202;53;76;225;57;206 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. All the individual TAMs, except L210W, occurred more frequently in d4T-exposed patients. 2015 PloS one Result HIV L210W 32 37 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Compared to d4T-exposed patients (n = 7), patients failing on a TDF-containing regimen (n = 43) were almost 5 times more likely to have a K65R mutation detected (aRR 4.86 95% CI 2.29-10.34, Table 2). 2015 PloS one Result HIV K65R 138 142 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Compared to patients in the NVP group (n = 8), patients under EFV pressure (n = 40) were 3.5 times more likely to present with a V106M mutation (aRR 3.53 95% CI 1.77-7.05. 2015 PloS one Result HIV V106M 129 134 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. In contrast the Y181C mutation was found in 47.1% (n = 32) and 6.5% (n = 6) of the NVP and EFV group respectively (aRR 0.16 95% CI 0.08-0.35. 2015 PloS one Result HIV Y181C 16 21 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. K70R was more frequently detected in d4T-exposed patients (15.0%, n = 12) as compared to the TDF-exposed group (8.8%, n = 7) but again, the difference was not significant. 2015 PloS one Result HIV K70R 0 4 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Nine of the 11 patients (82.0%) who developed the Y115F also developed the K65R mutation. 2015 PloS one Result HIV K65R;Y115F 75;50 79;55 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Similarly, only one (1.3%) TDF-exposed patient carried Q151M, co-existing with K65R, but this difference was not statistically significant. 2015 PloS one Result HIV K65R;Q151M 79;55 83;60 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Six (7.5%) TDF-exposed patients and two (2.5%) patients failing a d4T-regimen harboured the K65R mutation in combination with TAMs. 2015 PloS one Result HIV K65R 92 96 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. The frequency of the P225H mutation was significantly higher in the patients taking EFV (16 of 92, 17.4%) compared to the NVP treatment group (3 of 68, 4.4%, aRR 4.68 95% CI 1.43-15.37. 2015 PloS one Result HIV P225H 21 26 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. The K103N mutation was the most common non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation. 2015 PloS one Result HIV K103N 4 9 NNRTI;NNRTI 39;87 75;92 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. The K70E mutation, which is known to be selected under TDF pressure, was present in 10 (12.5%) of the TDF-exposed patients as compared to only two (2.5%) of the d4T-exposed patients (not significant). 2015 PloS one Result HIV K70E 4 8 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. The most common NRTI mutation in both the d4T- and TDF-exposed patients was M184V/I (n = 74, 92.5% and n = 72, 90.0% respectively), with M184V as the predominant mutation. 2015 PloS one Result HIV M184I;M184V;M184V 76;76;137 83;83;142 NRTI 16 20 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. The Q151M mutation was detected in five (6.3%) d4T-exposed patients, and in one of these patients Q151M occurred in combination with K65R. 2015 PloS one Result HIV K65R;Q151M;Q151M 133;4;98 137;9;103 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. A slight reduction in cleavage efficiency was observed with the double-mutant N348I/T369I. 2015 Nucleic acids research Result HIV N348I;T369I 78;84 83;89 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Additional experiments also showed that the differences between WT, N348I and N348I/T369I RTs were reduced when the assays were carried out in the presence of nevirapine or efavirenz (Supplementary Figure S3). 2015 Nucleic acids research Result HIV N348I;N348I;T369I 68;78;84 73;83;89 RT 90 93 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. As described above for the PPT29RNA/PPT28DNA complex, the N348I RT shows reduced cleavage efficiency at this position, while the activity of the double mutant is considerably reduced. 2015 Nucleic acids research Result HIV N348I 58 63 RT 64 66 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. As shown in Figure 1A, RT connection subdomain mutations T369I, T369V and T376S had a minor effect on the RT's ability to cleave the PPT17r8d oligonucleotide at position -17 (G A site) that corresponds to the RNA(PPT)-DNA junction. 2015 Nucleic acids research Result HIV T369I;T369V;T376S 57;64;74 62;69;79 RT;RT 23;106 25;108 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. As shown in Figure 3A, the PPT29RNA in the 29/28mer hybrid was efficiently cleaved at position -16 in reactions carried out with the WT RT and the single mutants T369I, T369V and T376S. 2015 Nucleic acids research Result HIV T369I;T369V;T376S 162;169;179 167;174;184 RT 136 138 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Both WT and N348I/T369I RTs showed similar PPT cleavage patterns in the presence of NNRTIs. 2015 Nucleic acids research Result HIV N348I;T369I 12;18 17;23 NNRTI;RT 84;24 90;27 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. E138K/N348I/T369I) (Supplementary Figure S5). 2015 Nucleic acids research Result HIV N348I;T369I;E138K 6;12;0 11;17;5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. However, as in the case of mutant T369I shorter PPT products of 16 and 15 nucleotides were also observed in reactions carried out with mutants T369V and T376S (data not shown). 2015 Nucleic acids research Result HIV T369I;T369V;T376S 34;143;153 39;148;158 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. However, cleavages at positions -17 and -18 were predominant in reactions carried out with the N348I/T369I RT, while all other RTs rendered a single product of 21 nucleotides (corresponding to RNAs cleaved at position -17) (Figure 3B). 2015 Nucleic acids research Result HIV N348I;T369I 95;101 100;106 RT;RT 107;127 109;130 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. However, NNRTI concentration influenced PPT removal in reactions carried out with both WT and the double-mutant N348I/T369I, with highest efficiencies at 0.6-5-muM nevirapine (Figure 2A and Supplementary Figure S1A). 2015 Nucleic acids research Result HIV N348I;T369I 112;118 117;123 NNRTI 9 14 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. However, the efficiency of this cleavage was almost negligible in reactions carried out with mutants N348I and N348I/T369I. 2015 Nucleic acids research Result HIV N348I;N348I;T369I 101;111;117 106;116;122 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. In addition, those authors demonstrated that N348I alone counteracts the effect of nevirapine, and to a lesser degree, efavirenz. 2015 Nucleic acids research Result HIV N348I 45 50 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. In contrast, in reactions carried out in the presence of rilpivirine, the endonucleolytic activity of mutants N348I and N348I/T369I was similar to that observed for the WT enzyme. 2015 Nucleic acids research Result HIV N348I;N348I;T369I 110;120;126 115;125;131 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. In order to test whether the observed differences in cleavage specificity between the mutant N348I/T369I and the other studied RTs could be attributed to the specific PPT sequence, we compared the RNase H cleavage patterns of WT and mutant RTs N348I and N348I/T369I using two heteropolymeric RNA/DNA template-primers. 2015 Nucleic acids research Result HIV N348I;N348I;N348I;T369I;T369I 93;244;254;99;260 98;249;259;104;265 RT;RT 127;240 130;243 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. In reactions carried out in the presence of dNTPs with the complex PPT29DNA/PPT17r that mimics the initial step of (+)-strand DNA synthesis, the mutant K103N RT was able to extend the RNA primer with similar efficiencies in the presence or absence of inhibitor (Supplementary Figure S1B). 2015 Nucleic acids research Result HIV K103N 152 157 RT 158 160 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Interestingly, cleavage patterns obtained with the N348I RT and template-primer PPT29RNA/PPT29DNA revealed its higher tendency to produce shorter oligonucleotides in comparison with the double mutant. 2015 Nucleic acids research Result HIV N348I 51 56 RT 57 59 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Interestingly, these inhibitory effects were not observed with a mutant RT that contained the rilpivirine resistance-associated mutation E138K combined with the two substitutions in the connection subdomain. 2015 Nucleic acids research Result HIV E138K 137 142 RT 72 74 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. N348I alone or in combination with T369I suppressed in part the enhancing effect of nevirapine and efavirenz on the RNase H activity of the enzyme. 2015 Nucleic acids research Result HIV T369I;N348I 35;0 40;5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. N348I, particularly in combination with T369I, showed very low efficiency in the RNase H cleavage reaction. 2015 Nucleic acids research Result HIV T369I;N348I 40;0 45;5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. On the other hand, in the presence of rilpivirine, we observed a significant inhibition of PPT extension with both WT and N348I/T369I RTs. 2015 Nucleic acids research Result HIV N348I;T369I 122;128 127;133 RT 134 137 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Overall cleavage efficiencies of N348I RT were similar to those determined for the WT enzyme (Supplementary Table S4), although the N348I mutant produced a smaller amount of secondary products. 2015 Nucleic acids research Result HIV N348I;N348I 33;132 38;137 RT 39 41 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Phenotypic assays carried out in MT-4 cells with recombinant HIV-1 bearing mutations N348I, T369I, T369V, T376S and the double mutant N348I/T369I were consistent with previous estimates and revealed that the double mutant shows significant resistance to nevirapine (Table 1). 2015 Nucleic acids research Result HIV N348I;N348I;T369I;T369I;T369V;T376S 85;134;92;140;99;106 90;139;97;145;104;111 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. PPT29RNA/PPT30DNA), all RTs showed identical cleavage patterns (Figure 3C) with similar RNase H catalytic rates, except for the single-mutant T369V that showed an increased kobs in comparison with the other enzymes (Supplementary Table S4). 2015 Nucleic acids research Result HIV T369V 142 147 RT 24 27 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Taken together, the analyses with template-primers of different lengths indicate that the combination of N348I and T369I has an impact on the RNase H cleavage window and reduces the RT's ability to produce shorter RNA products. 2015 Nucleic acids research Result HIV N348I;T369I 105;115 110;120 RT 182 184 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The combination of N348I and T369I affects the RNase H cleavage window of the HIV-1 RT. 2015 Nucleic acids research Result HIV N348I;T369I 19;29 24;34 RT 84 86 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The HIV-1 RT mutation K103N confers high-level resistance to nevirapine and efavirenz due to the inability of those drugs to bind the mutant RT. 2015 Nucleic acids research Result HIV K103N 22 27 RT;RT 10;141 12;143 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The selection of N348I and other mutations under therapy with NNRTIs, particularly with nevirapine, could be related to effects in other steps of the reverse transcription process. 2015 Nucleic acids research Result HIV N348I 17 22 RT;NNRTI 150;62 171;68 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. These results are consistent with an impaired ability to cleave shorter RNAs by the double-mutant N348I/T369I RT. 2015 Nucleic acids research Result HIV N348I;T369I 98;104 103;109 RT 110 112 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. These results were broadly consistent with the IC50 values obtained with recombinant RTs in nucleotide incorporation reactions using heteropolymeric DNA/DNA template-primers, although the N348I/T369I RT showed low-level resistance to rilpivirine in these assays (Supplementary Table S3). 2015 Nucleic acids research Result HIV N348I;T369I 188;194 193;199 RT;RT 85;200 88;202 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Thus, although the RNase H activity of the N348I/T369I RT is very low, addition of NNRTIs enhances its RNase H activity to similar levels as those observed with the WT RT. 2015 Nucleic acids research Result HIV N348I;T369I 43;49 48;54 NNRTI;RT;RT 83;55;168 89;57;170 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Thus, the 21-base oligonucleotide represented 25.4% of all cleavage products, while this value was reduced to 13.9% in reactions catalyzed by the N348I/T369I RT. 2015 Nucleic acids research Result HIV N348I;T369I 146;152 151;157 RT 158 160 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Unlike the WT RT, the combination of mutations N348I and T369I facilitates the extension of the PPT primer to produce a full-length product of 29 nucleotides in the presence of nevirapine (Figure 4B). 2015 Nucleic acids research Result HIV N348I;T369I 47;57 52;62 RT 14 16 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. We analyzed whether the reduced efficiency of PPT cleavage shown by mutant RTs N348I and N348I/T369I could be related to the positioning of the susceptible G A cleavage site in the RNA template relative to the DNA polymerase active site. 2015 Nucleic acids research Result HIV N348I;N348I;T369I 79;89;95 84;94;100 Pol;RT 214;75 224;78 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. A salient observation of the study is the presence of the L74I mutation, which confers high level of resistance to didanosine, in a drug naive patient (AIIMSU63). 2015 Viruses Result HIV L74I 58 62 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Interestingly, the viral RT gene from an ART naive patient (AIIMSPD11) had K101E and G190A double drug resistance mutations that are associated with high resistance to two commonly used NNRTI drugs, nevirapine and efavirenz. 2015 Viruses Result HIV G190A;K101E 85;75 90;80 NNRTI;RT 186;25 191;27 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. M184V mutation, which leads to high-level resistance to lamivudine and emtricitabine, was found in two ART treated children (AIIMSU35 and AIIMSU56). 2015 Viruses Result HIV M184V 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Two ART treated patients, AIIMSU30 (D67E and L74Y) and AIIMSU52 (K65E and D67G) had two mutations in the RT gene, known to confer resistance to NRTI drugs. 2015 Viruses Result HIV D67E;D67G;K65E;L74Y 36;74;65;45 41;78;70;49 NRTI;RT 144;105 148;107 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. By considering the residues with maximum variations in their orientational correlations that are below the lower standard deviation bound (average minus one standard deviation), it is assessed that the average correlation coefficient value which is 0.45 between NC-p1WT and NC-p1V82A increases to 0.58 between NC-p1WT and AP2VNC-p1V82A in the slowest mode. 2015 Evolutionary applications Result HIV V82A;V82A 279;331 283;335 NC;NC;NC 262;274;310 264;276;312 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Figure4 displays the orientational correlation values of the fluctuation vectors of protease residues of NC-p1V82A and AP2VNC-p1V82A with respect to NC-p1WT for the slowest two modes. 2015 Evolutionary applications Result HIV V82A;V82A 110;128 114;132 PR;NC;NC 84;105;149 92;107;151 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Furthermore, the variations in the fluctuation directions of the hinge residues of AP2VNC-p1V82A remain within the variations observed in NC-p1WT compared to those observed in NC-p1V82A. 2015 Evolutionary applications Result HIV V82A;V82A 92;181 96;185 NC;NC 138;176 140;178 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Here, it is interesting to note the higher number of protease residues in NC-p1V82A and AP2VNC-p1V82A possessing higher correlations with those in the wild-type complex structures bound to the rest of the natural substrates. 2015 Evolutionary applications Result HIV V82A;V82A 79;97 83;101 PR;NC 53;74 61;76 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Here, within the NC-p1 structures in the slowest two modes, higher correlation is observed in most of the hinge residues between wild-type and coevolved complex structures compared to that between wild-type and V82A mutant, resembling the orientational correlations within the p1-p6 structures. 2015 Evolutionary applications Result HIV V82A 211 215 NC;Gag 17;280 19;282 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. In both modes, the correlation of p1-p6D30N with p1-p6WT is even less than that of p1-p6D30N/N88D which has the signature mutations of nelfinavir resistance that occur in association with p1-p6 cleavage site mutations (Kolli et al.). 2015 Evolutionary applications Result HIV D30N;D30N;N88D 39;88;93 43;92;97 Gag;Gag;Gag 37;86;191 39;88;193 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. In the most cooperative modes of motion of these structures, the maximum orientational variations are observed in the same residues that lie along the hinge axes in p1-p6WT where the directions of their fluctuations are significantly distorted in p1-p6D30N/N88D. 2015 Evolutionary applications Result HIV D30N;N88D 252;257 256;261 Gag 250 252 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. In the second slowest mode, the average coefficient value does not improve much (0.026-0.052, respectively) for the correlations of NC-p1WT with NC-p1V82A and AP2VNC-p1V82A. 2015 Evolutionary applications Result HIV V82A;V82A 150;168 154;172 NC;NC 132;145 134;147 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. In the slowest mode, the correlations of residues 66, 69, 89, 92, 93, 77', 89', and 93' between AP2VNC-p1V82A and NC-p1WT are higher than their correlations between NC-p1V82A and NC-p1WT (Fig.4B,C). 2015 Evolutionary applications Result HIV V82A;V82A 105;170 109;174 NC;NC;NC 114;165;179 116;167;181 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. In the slowest mode, the higher correlation values of residues 67, 68, 69, 56', and 78' between LP1'Fp1-p6D30N/N88D and p1-p6WT structures compared to those between p1-p6D30N/N88D and p1-p6WT structures are evident (Fig.3B,C). 2015 Evolutionary applications Result HIV D30N;D30N;N88D;N88D 106;170;175;111 110;174;179;115 Gag;Gag 104;168 106;170 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. It appears that the correlation between the NC-p1 complex structure with the other natural substrate bound structures increases as a result of the mutation V82A in the protease. 2015 Evolutionary applications Result HIV V82A 156 160 PR;NC 168;44 176;46 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. On the other hand, these variations in the fluctuation directions of the hinge residues of LP1'Fp1-p6D30N/N88D largely remain within the variations observed in p1-p6WT compared to those observed in p1-p6D30N/N88D. 2015 Evolutionary applications Result HIV D30N;D30N;N88D;N88D 101;203;106;208 105;207;110;212 Gag;Gag 99;201 101;203 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Similarly, in the second slowest mode, the average correlation coefficient value between p1-p6WT and p1-p6D30N/N88D is 0.63, whereas it is 0.69 between p1-p6WT and LP1'Fp1-p6D30N/N88D. 2015 Evolutionary applications Result HIV D30N;D30N;N88D;N88D 106;174;111;179 110;178;115;183 Gag;Gag 104;172 106;174 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. That is, the AP2V mutation on the peptide coevolving with the V82A mutation on the protease re-orients the peptide to a conformation which is more similar to those of the other natural substrate-protease complexes than the NC-p1 (Prabu-Jeyabalan et al.). 2015 Evolutionary applications Result HIV V82A 62 66 PR;PR;NC 83;195;223 91;203;225 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The correlation coefficients calculated over the least correlating residues (having correlation values below the lower standard deviation bound) are 0.64, 0.84, and 0.87 in the slowest mode and 0.32, 0.59, and 0.57 in the second slowest mode in turn for NC-p1WT, NC-p1V82A, and AP2VNC-p1V82A with respect to the average of the wild-type structures of the other six natural substrates. 2015 Evolutionary applications Result HIV V82A;V82A 268;287 272;291 NC;NC 254;263 256;265 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The correlation coefficients of the residue fluctuation vectors between NC-p1WT and AP2VNC-p1V82A in both modes are higher than they are between NC-p1WT and NC-p1V82A, yet the increases in the correlations are not as significant as in p1-p6. 2015 Evolutionary applications Result HIV V82A;V82A 93;162 97;166 NC;NC;NC;Gag 72;145;157;238 74;147;159;240 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The correlation coefficients of the residue fluctuation vectors between p1-p6WT and LP1'Fp1-p6D30N/N88D in both modes are in general higher than they are between p1-p6WT and p1-p6D30N/N88D. 2015 Evolutionary applications Result HIV D30N;D30N;N88D;N88D 94;179;99;184 98;183;103;188 Gag;Gag 92;177 94;179 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The orientational correlation of protease residues of NC-p1WT, NC-p1V82A, and AP2VNC-p1V82A with respect to the average of the wild-type structures of the other six natural substrates in the two most cooperative modes of motion is displayed in Fig.5. 2015 Evolutionary applications Result HIV V82A;V82A 68;87 72;91 PR;NC;NC 33;54;63 41;56;65 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The residue fluctuations in the slowest two modes of p1-p6D30N, p1-p6D30N/N88D, and LP1'Fp1-p6D30N/N88D variants are compared with those of p1-p6WT (Fig.3). 2015 Evolutionary applications Result HIV D30N;D30N;D30N;N88D;N88D 58;69;94;74;99 62;73;98;78;103 Gag;Gag;Gag 56;67;92 58;69;94 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The residues that display the maximum variations between the directions of fluctuations can also be visualized on the structures in Fig.3, as color coded according to the change in the correlation values of p1-p6D30N/N88D (Fig.3B,E) and LP1'Fp1-p6D30N/N88D (Fig.3C,F) compared to p1-p6WT. 2015 Evolutionary applications Result HIV D30N;D30N;N88D;N88D 212;247;252;217 216;251;256;221 Gag;Gag 210;245 212;247 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The residues that lie along the hinge axes affirm maximum orientational variations with significant distortions in the directions of their fluctuations in NC-p1V82A in the most cooperative modes of motion. 2015 Evolutionary applications Result HIV V82A 160 164 NC 155 157 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The residues with maximum orientational differences between their directions of fluctuations can also be observed on the structures in Fig.5, as color coded according to the change in the correlation of the NC-p1WT (Fig.5B,E) and AP2VNC-p1V82A (Fig.5C,F) compared to the average of the wild-type protease structures bound to the other six natural substrates. 2015 Evolutionary applications Result HIV V82A 239 243 PR;NC 296;207 304;209 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The structures in Fig.4 display the residues that exhibit the maximum variations between the directions of fluctuations, as color coded according to the change in the correlation values of NC-p1V82A (Fig.4B,E) and AP2VNC-p1V82A (Fig.4C,F) compared to NC-p1WT. 2015 Evolutionary applications Result HIV V82A;V82A 194;223 198;227 NC;NC 189;251 191;253 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The structures of NC-p1 bound protease studied here are the representative conformations of the largest of four, three, and five clusters in NC-p1WT, NC-p1V82A, and AP2VNC-p1V82A MD simulation trajectories, respectively (Table1). 2015 Evolutionary applications Result HIV V82A;V82A 155;174 159;178 PR;NC;NC;NC 30;18;141;150 38;20;143;152 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The structures of p1-p6 bound protease studied here are the representative conformations of the largest of five, three, and four clusters in p1-p6WT, p1-p6D30N/N88D, and LP1'Fp1-p6D30N/N88D MD simulation trajectories, respectively (Table1). 2015 Evolutionary applications Result HIV D30N;D30N;N88D;N88D 155;180;185;160 159;184;189;164 PR;Gag;Gag;Gag 30;21;153;178 38;23;155;180 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. This is consistent with the structural rationale for HIV-1 protease binding to the NC-p1 cleavage site given in Prabu-Jeyabalan's work (Prabu-Jeyabalan et al.), where they solved the crystal structures of wild-type and V82A mutant proteases in complex with their respective wild-type and AP2V mutant NC-p1 substrates. 2015 Evolutionary applications Result HIV V82A 219 223 PR;PR;NC;NC 59;231;83;300 67;240;85;302 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. To quantify, when the residues with maximum variations in their orientational correlations that are below the lower standard deviation bound (average minus one standard deviation) are considered, the average correlation coefficient value which is 0.61 between p1-p6WT and p1-p6D30N/N88D increases to 0.90 between p1-p6WT and LP1'Fp1-p6D30N/N88D in the slowest mode. 2015 Evolutionary applications Result HIV D30N;D30N;N88D;N88D 277;335;282;340 281;339;286;344 Gag;Gag 275;333 277;335 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Alignments for compounds 1 and 2 in the RT (WT), RT (Y181C), and RT (K103N/Y181C) structures show the differences between the ethoxy uracil side chain for the sag and aag conformations (Figure 3). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 69;53;75 74;58;80 RT;RT;RT 40;49;65 42;51;67 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. All atom alignments of the inhibitor and binding pockets for wild-type and mutant-inhibitor complexes (Figure 1) reveal the lack of global conformational changes imparted by the resistance mutations K103N and Y181C, which was also observed in earlier complexes determined for RT (K103N/Y181C):rilpivirine (PDB code: 3BGR), RT (Y181C):nevirapine (PDB code: 1JLB), RT (K103N):rilpivirine (PDB code: 3MEG), and RT(K103N):etravirine (PDB code: 3MED). 2015 Journal of medicinal chemistry Result HIV K103N;K103N;K103N;K103N;Y181C;Y181C;Y181C 199;280;367;411;209;286;327 204;285;372;416;214;291;332 RT;RT;RT;RT 276;323;363;408 278;325;365;410 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Although compound 2 can form only three hydrogen bonds in the RT (WT):2 structure, as compared with the possible four hydrogen bonds formed in the RT (WT):1 structure, the aag conformation allows for the maintenance of two hydrogen bonds in RT (Y181C) and RT (K103N/Y181C) structures. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 260;245;266 265;250;271 RT;RT;RT;RT 62;147;241;256 64;149;243;258 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Although the difference of a single Cl atom may seem like a minor change, it has major consequences on how compound 1 adapts in the Y181C and K103N/Y181C binding pockets. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 142;132;148 147;137;153 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Although the sag conformation seems favorable in the RT (WT):1 structure, as observed by the multiple hydrogen bonds formed between the uracil ring and Lys102, Lys103, and Pro236 (Figure 4), it seems that this conformation is unfavorable in the RT (Y181C):1 and RT (K103N/Y181C):1 structure complexes. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 266;249;272 271;254;277 RT;RT;RT 53;245;262 55;247;264 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. An all atom superposition of the three binding pockets in complex with 1 (Figure 1A) reveals slight differences in binding conformations in which the compound shifts toward the pocket opening created by the Cys181 mutation in RT (Y181C):1 and RT (K103N/Y181C):1 structures (Figure 2B,C). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 247;230;253 252;235;258 RT;RT 226;243 228;245 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. As observed in the assay data for compound 1, an 890-fold decrease in activity was observed for the RT (Y181C) variant compared with RT (WT), and an even greater 4000-fold decrease in activity was observed for the RT (K103N/Y181C) variant compared with RT (WT). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 218;104;224 223;109;229 RT;RT;RT;RT 100;133;214;253 102;135;216;255 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. As summarized in Table 1, compound 2 has an EC50 of 0.310 nM for RT (WT), 46 nM for RT (Y181C), and 24 nM for RT (K103N/Y181C). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 114;88;120 119;93;125 RT;RT;RT 65;84;110 67;86;112 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Balancing both optimal activity for RT variants and solubility, complexes with both compounds 1 and 2 were determined to understand how removal of the 5-Cl group allowed for the maintenance of potency with RT (Y181C) and RT (K103N/Y181C). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 225;210;231 230;215;236 RT;RT;RT 36;206;221 38;208;223 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Despite the dramatic change in EC50 values, both compounds 1 and 2 retain several van der Waals and hydrophobic interactions in the RT (Y181C) and RT (K103N/Y181C) binding pockets. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 151;136;157 156;141;162 RT;RT 132;147 134;149 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Despite the elimination of crucial pi-pi stacking between the catechol aryl and Tyr181, compound 2 maintains a similar conformation in the RT (WT), RT (Y181C), and RT (K103N/Y181C) structures (Figure 1B, 3,4). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 168;152;174 173;157;179 PI;PI;RT;RT;RT 35;38;139;148;164 37;40;141;150;166 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. General Structure Details for RT (WT), RT (Y181C), and RT (K103N/Y181C) 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 59;43;65 64;48;70 RT;RT;RT 30;39;55 32;41;57 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. General Structure Details for RT (WT), RT (Y181C), and RT (K103N/Y181C). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 59;43;65 64;48;70 RT;RT;RT 30;39;55 32;41;57 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. However, the structures interpreted here represent low energy conformations that may assist in the understanding of which compound orientation is favorable against the RT (Y181C) and RT (K103N/Y181C) binding pockets. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 187;172;193 192;177;198 RT;RT 168;183 170;185 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In comparing the RT (WT), RT (Y181C), and RT (K103N/Y181C) structures with 2, the interaction between the NH3+ side chain of K102 and O4 of the uracil carbonyl is not identified in the crystal structures (Figure 4). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 46;30;52 51;35;57 RT;RT;RT 17;26;42 19;28;44 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In comparing the three binding modes of 1 in the structures, in which the ethoxy uracil is in the sag conformation, the compound seems to shift in the RT (Y181C) and RT (K103N/Y181C) complexes. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 170;155;176 175;160;181 RT;RT 151;166 153;168 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Initially, we used cocrystallization methods and optimization conditions similar to those reported earlier for RT (WT) crystals- to form RT (Y181C) and RT (K103N/Y181C) crystals. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 156;141;162 161;146;167 RT;RT;RT 111;137;152 113;139;154 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Instead, Val179 in both RT (Y181C):2 and RT (K103N/Y181C):2 structures adopts a rotamer conformation amenable for a VDW interaction with the catechol aryl. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 45;28;51 50;33;56 RT;RT 24;41 26;43 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Observed only in the mutant complexes with compound 1, the uracil ring rotates ~40 in the RT (Y181C):1 and RT (K103N/Y181C):1 complexes (Figure 1A, Figure S2A) in which the O2 of the uracil carbonyl in RT (WT) and RT (Y181C)/RT (K103N/Y181C) structures serves as a reference point. 2015 Journal of medicinal chemistry Result HIV K103N;K103N;Y181C;Y181C;Y181C;Y181C 112;230;95;118;219;236 117;235;100;123;224;241 RT;RT;RT;RT;RT 91;108;203;215;226 93;110;205;217;228 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Previously, we reported the antiviral activity for compounds 1 and 2 in MT-2 cells infected with HIV-1 virus containing RT (WT), RT (Y181C), and RT (K103N/Y181C) variants. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 149;133;155 154;138;160 RT;RT;RT 120;129;145 122;131;147 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Similarly, this same interaction is farther apart, with distances of 3.9 A for RT (Y181C):2 and 3.8 A RT (K103N/Y181C):2. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 106;83;112 111;88;117 RT;RT 79;102 81;104 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Similarly, we determined three additional crystal structures of RT (WT), RT (Y181C), and RT (K103N/Y181C) in complex with 2 to compare with the complexes of 1 (Table 2). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 93;77;99 98;82;104 RT;RT;RT 64;73;89 66;75;91 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Slight changes in rotamer conformation are observed in the mutant pockets most likely as a result of the changing spatial environment imparted by the K103N and Y181C mutations. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C 150;160 155;165 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The elimination of the 5-Cl from the catechol ring led to compound 2, an analogue that maintains significantly better potency against RT (Y181C) and RT (K103N/Y181C) variants. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 153;138;159 158;143;164 RT;RT 134;149 136;151 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The interaction between Tyr181 and the CG of Pro95 observed in the RT (WT):1 and RT (WT):2 structures is lost, with the Cys181 mutation causing a rotamer change from CG endo (WT) to CG exo as observed in the RT (Y181C) and RT (K103N/Y181C) structures. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 227;212;233 232;217;238 RT;RT;RT;RT 67;81;208;223 69;83;210;225 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The interaction with Val179 and catechol ring identified in the mutant complexes with 2 may help stabilize the aag conformation, which seems to maintain better activity for RT (WT), RT (Y181C) and RT (K103N/Y181C) variants. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 201;186;207 206;191;212 RT;RT;RT 173;182;197 175;184;199 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The opening in the pocket caused by the Cys181 mutation weakens the interaction between the 5-Cl and CG of Pro95; the distances between these atoms in the RT (Y181C):1 and RT (K103N/Y181C):1 complexes are now 3.8 and 3.9 A, respectively. 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 176;159;182 181;164;187 RT;RT 155;172 157;174 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The overall surface area for this region is reduced by 41-58 A2 (Table S2) in the RT (Y181C) and RT (K103N/Y181C) structures as compared with the RT (WT) structures, where Tyr181 is present (Table S2). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 101;86;107 106;91;112 RT;RT;RT 82;97;146 84;99;148 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The sag conformation of 1 is compromised by the Cys181 mutation, in which only 2 hydrogen bonds are observed in the RT (Y181C):1 structure, and only 1 hydrogen bond is observed in the RT (K103N/Y181C):1 structure (Figure 4). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 188;120;194 193;125;199 RT;RT 116;184 118;186 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. This Val179 interaction is lost with Cys181, and concurrently, the VDW interaction between the 5-Cl of compound 1 and the CG1 atom of Val179 (which is ~3.3 A) in the RT (WT) structures is lost in the RT (Y181C) and RT (K103N/Y181C) structure (distance is now 3.9 and 4.1 A, respectively). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 219;204;225 224;209;230 RT;RT;RT 166;200;215 168;202;217 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. To avoid steric clash with the 5-Cl, Val179 adopts a different rotamer conformation in the RT (Y181C) and RT (K103N/Y181C) structures in which the CG1 and CG2 atoms in the side chain rotate ~180 compared with the original orientation observed in the RT (WT) structure (Figure S2A). 2015 Journal of medicinal chemistry Result HIV K103N;Y181C;Y181C 110;95;116 115;100;121 RT;RT;RT 91;106;251 93;108;253 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. To elucidate the effects of K103N and Y181C mutations on inhibitor binding, we determined crystal structures of RT (Y181C) and RT (K103N/Y181C) in complex with compound 1 to compare with the previously determined RT (WT):1 crystal structure (PDB code: 4H4M). 2015 Journal of medicinal chemistry Result HIV K103N;K103N;Y181C;Y181C;Y181C 28;131;38;116;137 33;136;43;121;142 RT;RT;RT 112;127;213 114;129;215 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. NNRTI resistance was mainly high level to efavirenz and nevirapine (at a frequency of 3-4%), largely reflecting the contribution of the K103N mutation. 2015 HIV medicine Result HIV K103N 136 141 NNRTI 0 5 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. NRTI mutations were overwhelmingly thymidine analogue mutations, particularly M41L and T215 revertants. 2015 HIV medicine Result HIV M41L 78 82 NRTI 0 4 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. Similarly, M46IL (42%; 22/52) and L90M (25%; 13/52) were the most common PI mutations. 2015 HIV medicine Result HIV L90M;M46I;M46L 34;11;11 38;16;16 PI 73 75 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. The M184VI (associated with lamivudine and emtricitabine exposure) and K65R (associated with didanosine, abacavir, and tenofovir exposure) mutations were not detected in any samples. 2015 HIV medicine Result HIV K65R;M184I;M184V 71;4;4 75;10;10 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. The most prevalent NNRTI mutation was K103NS, observed in 62% (53/85) of samples that harboured virus with resistance to this class. 2015 HIV medicine Result HIV K103N;K103S 38;38 44;44 NNRTI 19 24 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Assessment of the relationship between host HLA B alleles, possession of A163X, and the associated KF11-specific CD8+ T-cell response revealed no evidence for superior T-cell response(s) in clade A1- than clade D-infected subjects. 2015 Vaccine Result HIV A163X 73 78 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Compensatory mutation S165N is known to partially restore A163X-associated impairment of virus replication. 2015 Vaccine Result HIV A163X;S165N 58;22 63;27 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Epitope polymorphisms occurred at the Serine residue 165 (S165N); and at Alanine residue 163 (A163X) where Alanine was substituted with Glycine (G: n = 13), Valine (V: n = 1) or Serine (S: n = 1). 2015 Vaccine Result HIV A163X;S165N 94;58 99;63 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. I147X compensatory mutation in the ISW9 epitope was more frequent in clade A1-infected patients. 2015 Vaccine Result HIV I147X 0 5 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. In HLAB*57 subjects with the A163X mutation, virus-specific CD8+ T-cell polyfunctionality were at similar frequencies across clades. 2015 Vaccine Result HIV A163X 29 34 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. ISW9 epitope polymorphisms comprised the A146X escape in the epitope flanking region (X = G, N, P, S or V); and the I147X compensatory mutations (where X = V, F, W or M), that are known to restore immune recognition of ISW9 (29). 2015 Vaccine Result HIV A146X;I147X 41;116 46;121 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Of 2 subjects with S165N, the clade D infected subject had higher plasma viral loads (UG017; 178,000 RNA copies/ml) than the clade A subject (UG065; 4240 RNA copies/ml). 2015 Vaccine Result HIV S165N 19 24 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Of the 8 HLA B*57/5801 subjects, A163X occurred in 80% clade A1 (4/5) compared to 0% in clade D (0/3); p = 0.03, Table 1. 2015 Vaccine Result HIV A163X 33 38 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Overall, A163X was found in 15 of 44 subjects (34%); comprising 61% (14/23) clade A1 and 5% (1/21) clade D; p = 0.00015, Fisher's Exact test. 2015 Vaccine Result HIV A163X 9 14 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Overall, I147X was found in 25% (11/44) subjects, comprising 43% (10/23) clade A1 infected, and 5% (1/21) clade D infected, irrespective of host HLA alleles; p = 0.007; Fisher's Exact test. 2015 Vaccine Result HIV I147X 9 14 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Overall, S165N mutation was less frequent (5%, 2/44). 2015 Vaccine Result HIV S165N 9 14 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Polymorphism A146X was found in 13/44 (30%) subjects, and occurred at comparable frequencies across clades A1- (30%, 7/23) and D (29%, 6/21), Table 1. 2015 Vaccine Result HIV A146X 13 18 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Polymorphisms in the TW10 epitope included escape mutation T242X in 16% of the subjects (where X = N [n = 4] or S [n = 3]); and the compensatory mutation G248X seen in 39% of the subjects (where X = A [n = 15], Q [n = 1] or T [n = 1];), Table 1. 2015 Vaccine Result HIV G248X;T242X 154;59 159;64 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. The KF11 epitope escape A X at Gag position 163 (A163X) was associated with clade A1 infected subjects irrespective of host alleles. 2015 Vaccine Result HIV A163X 51 56 Gag 33 36 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. The presence of A163X was associated with clade A1 infected subjects. 2015 Vaccine Result HIV A163X 16 21 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. There was no significant difference between frequencies of T242X ([4%; 1/23] vs. 2015 Vaccine Result HIV T242X 59 64 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Therefore, I147L is not considered to be a polymorphism in our I147X analyses. 2015 Vaccine Result HIV I147L;I147X 11;63 16;68 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Two of eight subjects with HLA B*57 and *5801 and A163X had detectable HIV-specific IFN-gamma responses. 2015 Vaccine Result HIV A163X 50 55 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. All the eleven combined PNGS mutants (except for M46) showed a 2-34-fold ID50 increase in 7-15 of the serum panels, with the mutant 197M.11 (N197D/N463Q/N625Q/N442Q/N339Q) showing 2-34 fold increase in 15 tested serum samples compare to the respective single PNGS mutants and wild-type virus. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N339Q;N442Q;N463Q;N625Q 141;165;159;147;153 146;170;164;152;158 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Among all the combined mutants studied here, only 197M.1 (N197D/N301Q) has completely lost infectivity. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N301Q 58;64 63;69 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Among the single PNGS mutants, N197D had a 2-3-fold ID50 increase in the seven sera of the serum panel; N301Q showed a 2-5-fold ID50 increase in eight of the serum panel; N442Q showed a 2-5-fold ID50 increase in seven of the serum panel; and the N625Q made a 2-4-fold ID50 increase in seven of the serum panel. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N301Q;N442Q;N625Q 31;104;171;246 36;109;176;251 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Another interesting observation is that, while some the single PNGS mutants showed no effect on neutralizing sensitivity by serum, combining such single PNGS mutants somehow displayed increased neutralizing sensitivity to serum antibodies, as shown by the sensitivity increase of mutants 197M.6 (N197D/N625Q/N442Q) and 197M.7 (N197D/N625Q/N442Q/N339Q) to serum sc59R, and mutants 197M.8 (N197D/N463Q/N625Q/N442Q/N339Q/N448), 197M.9 (N197D/N463Q/N625Q/N442Q/N339Q) and 197M.10 (N197D/N463Q/N625Q/N442Q/N339Q/N466Q) to serum gx93 (Table 2). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N197D;N197D;N197D;N197D;N339Q;N339Q;N339Q;N339Q;N442Q;N442Q;N442Q;N442Q;N442Q;N463Q;N463Q;N463Q;N466Q;N625Q;N625Q;N625Q;N625Q;N625Q 296;327;388;433;477;345;412;457;501;308;339;406;451;495;394;439;483;507;302;333;400;445;489 301;332;393;438;482;350;417;462;506;313;344;411;456;500;399;444;488;512;307;338;405;450;494 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. As for the antibody neutralization, nMAb b12 relies solely on heavy chain contacts that partially overlap with the CD4 binding site, and unlike the VRC antibodies, neutralization of HIV FE by b12 is not as dramatically affected by FE gp120 N197D/N463Q mutation. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N463Q;N197D 246;240 251;245 gp120 234 239 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Eleven of the twelve mutants (except for M46) contain the N197D mutation, and eight of them contain N197D/N463Q mutations. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N197D;N463Q 58;100;106 63;105;111 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. For example, mutants 197M.3 (N197D/N463Q), 197M.4 (N197D/N463Q/N442Q), 197M.5 (N197D/N463Q/N625Q), 197M.8 (N197D/N463Q/N625Q/N442Q/N339Q/N448) and 197M.9 (N197D/N463Q/N625Q/N442Q/N339Q) showed a 867-fold increase in susceptibility to neutralization by VRC03 when compared with wild-type, whereas mutants 197M.10 (N197D/N463Q/N625Q/N442Q/N339Q/N466Q) and 197M.11 (N197D/N463Q/N625Q/N442Q/N339Q) showed a ~1300-fold increase, and 197M.2 (N197D/N625Q), 197M.6 (N197D/N625Q/N442Q) and 197M.7 (N197D/N625Q/N442Q/N339Q) showed a ~100-fold increase (Table 1. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N197D;N197D;N197D;N197D;N197D;N197D;N197D;N339Q;N339Q;N339Q;N339Q;N339Q;N442Q;N442Q;N442Q;N442Q;N442Q;N442Q;N442Q;N463Q;N463Q;N463Q;N463Q;N463Q;N463Q;N466Q;N625Q;N625Q;N625Q;N625Q;N625Q;N625Q;N625Q;N197D;N197D;N463Q;N625Q 51;79;107;155;313;363;458;489;131;179;337;387;507;63;125;173;331;381;470;501;57;85;113;161;319;369;343;91;119;167;325;375;464;495;29;436;35;442 56;84;112;160;318;368;463;494;136;184;342;392;512;68;130;178;336;386;475;506;62;90;118;166;324;374;348;96;124;172;330;380;469;500;34;441;40;447 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. For the sensitivity to b12, similar to the behavior of the FE strain mutants, the combined N197Q and N463Q mutations in these two clade viruses showed no obvious changes when compared with the N197Q single mutant (Supplemental. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197Q;N197Q;N463Q 91;193;101 96;198;106 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. However, all other combined PNGS mutants containing N197D mutation showed little changes of sensitivity to b12 or other nMAbs (PG9, PG16, 2F5, 4E10 and 2G12) when compared to the N197D single point mutant (Table 1. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N197D 52;179 57;184 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. However, the neutralization result for the eight combined PNGS mutants in this study showed a much more dramatic increase in susceptibility to neutralization by VRC01/VRC03 compared to the single N197D or to wild-type (Table 1. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D 196 201 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. In addition, the N611Q mutant was neutralized by serum gx66, gx76 with a titer increase of over three-fold compared to the wild-type virus, and the N637Q mutant was neutralized by serum yn148r with a five-fold titer increase compared to the wild-type virus. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N611Q;N637Q 17;148 22;153 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. In order to understand the molecular basis for the observed increase of sensitivity to VRC01/VRC03 when N463Q mutation is added on top of N197D, we analyzed the available structural information for gp120 structures alone and its complexes with CD4 and various nMAbs. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N463Q 138;104 143;109 gp120 198 203 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. In previous work, the single N197D mutant showed an obvious increase in susceptibility to neutralization by b12 (~17-fold increase) and VRC03 (~37-fold increase), as well as a modest 2-fold increase to VRC01 when compared to wild-type. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D 29 34 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. M46 (N625Q/N463Q) showed no effect on VRC01/VRC03 mediated neutralization. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N463Q;N625Q 11;5 16;10 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Other multiple mutants showed no significant reduction of viral infectivity when compared to the two single point mutants, N197D or N301Q. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N301Q 123;132 128;137 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. The combination of N197Q and N463Q showed a less dramatic, but still significant increase in susceptibility to neutralization by VRC01/VRC03, ranging between 8 to 20 fold increase. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197Q;N463Q 19;29 24;34 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. The N197D mutation resulted a 2-fold reduction in serum xj50 neutralization, this neutralization reduction also happened in the N611Q mutation to serum yn99r, N289D to serum bj22 and gx75, N448Q to serum sc59r and N625Q to serum yn99r. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N289D;N448Q;N611Q;N625Q 4;159;189;128;214 9;164;194;133;219 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. The N197Q mutation alone in the two viruses showed a ~2-4 fold increase in susceptibility to neutralization by VRC01/VRC03, whereas the N463Q mutation alone showed no effect (Supplemental. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197Q;N463Q 4;136 9;141 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. The non-infectious mutant 197M.1 (N197D/N301Q) was excluded from the further neutralization assay study. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197D;N301Q 34;40 39;45 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. The results shown above indicate that whenever a combined mutant of the HIV FE strain (a BC clade virus) contains N197Q together with N463Q, a dramatic increase of the neutralizing sensitivity to VRC01/VRC03 is observed. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197Q;N463Q 114;134 119;139 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. To investigate whether the combination of N197Q and N463Q mutation has the same effect in other clade viruses to these CD4bs MAbs neutralization, a clade B virus B05 and a clade AE virus GX74.20 were tested. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV N197Q;N463Q 42;52 47;57 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. A wide range of mutations conferring multi-NRTI resistance were also observed, including M41L (n = 7, 10%), A62V (n = 15, 22%), D67N (n = 10, 15%), K70R (n = 10, 15%), V75I (n = 2, 3%), F77L (n = 1, 1%), Y115F (n = 6, 9%), F116Y (n = 1, 1%), Q151M (n = 1, 1%), L210W (n = 3, 4%), T215Y/F (n = 7, 10%) and (n = 5, 7%), and K219Q/E (n = 4, 6%) and (n = 7, 10%). 2015 Journal of medical virology Result HIV A62V;D67N;F116Y;F77L;K219E;K219Q;K70R;L210W;M41L;Q151M;T215F;T215Y;V75I;Y115F 108;128;223;186;322;322;148;261;89;242;280;280;168;204 112;132;228;190;329;329;152;266;93;247;287;287;172;209 NRTI 43 47 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. As expected, the most common NRTI DRM was M184V (selected by 3TC and FTC) present in 60 patient isolates (88%), followed by K65R (selected by TDF, d4T, abacavir [ABC], didanosine [DDI]) (n = 21, 31%). 2015 Journal of medical virology Result HIV K65R;M184V 124;42 128;47 NRTI 29 33 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. Of note, there was a high prevalence of Y181C/I/V (n = 28, 41% cumulatively) that confers reduced susceptibility to both rilpivirine (RPV) and etravirine (ETR), and Y188L (n = 5, 7%) which leads to reduced susceptibility to RPV. 2015 Journal of medical virology Result HIV Y181C;Y181I;Y181V;Y188L 40;40;40;165 49;49;49;170 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. The most prevalent NNRTI mutations were Y181C/I/V (n = 24, 35%), (n = 3, 4%), and (n = 1 (1%), respectively, K103N/S (n = 21 (32%) and n = 1 [1%]), G190A/S/E (n = 20 (29%), n = 1 (1%), and (n = 2, 3%), respectively, V108I (n = 13, 19%), and V106A/M (n = 2, 3%) and (n = 10, 15%). 2015 Journal of medical virology Result HIV G190A;G190E;G190S;K103N;K103S;V106A;V106M;V108I;Y181C;Y181I;Y181V 148;148;148;109;109;241;241;216;40;40;40 157;157;157;116;116;248;248;221;49;49;49 NNRTI 19 24 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. V82A was detected in all three patients, with concurrent M46I, Q58E, and L76V in one of the three patients harboring the clade J HIV-1 virus. 2015 Journal of medical virology Result HIV L76V;M46I;Q58E;V82A 73;57;63;0 77;61;67;4 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Accordingly, we examined whether the TAMs D67N/K70R increase errors introduced by HIV-1 RT during intracellular RTn that are alleviated by silent mutations K65K and K66K. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 42;156;165;47 46;160;169;51 RT 88 90 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Accordingly, we investigated whether HIV-1 harboring K65K or K66K (AAA to AAG change) in the presence of the TAMs, D67N and K70R (HIVTAMK65K and HIVTAMK66K, respectively), potentiated resistance to RT inhibitors. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 115;53;61;124 119;57;65;128 RT 198 200 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Additionally, MNVs emerged in HIVWT during single-cycle infections, with the most frequent MNV located at nucleotide 2744 (RT codon 65) culminating in the emergence of K65K and D67N in the same read (0.3%; Figure 5C and Supplementary Table S2). 2015 Nucleic acids research Result HIV D67N;K65K 177;168 181;172 RT 123 125 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Based on our previous data showing that K65K and K66K alleviate pausing of recombinant HIV-1 RT during cDNA synthesis of a synthetic RNA template containing D67N/K70R, we hypothesized that these silent mutations overcome a HIV-1 fitness defect conferred by the TAMs D67N/K70R. 2015 Nucleic acids research Result HIV D67N;D67N;K65K;K66K;K70R;K70R 157;266;40;49;162;271 161;270;44;53;166;275 RT 93 95 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. HIV-1 harboring TAMs D67N/K70R in the absence or presence of the K65K or K66K silent mutations generated by transfection did not lead to significant decreases in viral infectivity, steady-state virion-associated RT protein levels or RT activity relative to WT virus (Supplementary Figures S2 and S3). 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 21;65;73;26 25;69;77;30 RT;RT 212;233 214;235 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. However, our data indicate that either the fitness advantage conferred by silent mutations does not affect RTn efficiency or that the single-cycle infection assay we employed lacked the sensitivity to measure subtle effects conferred by K65K and K66K. 2015 Nucleic acids research Result HIV K65K;K66K 237;246 241;250 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. In addition, part of the capsid coding region was sequenced, which confirmed the absence of the H87Q mutation reported to confer a replication advantage to HIV-1 in cyclophilin A-rich cells such as MT-2. 2015 Nucleic acids research Result HIV H87Q 96 100 Capsid 25 31 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. In HIVWT, a homopolymeric region of six adenines exists at RT codons 65 and 66 that would be disrupted by K65K and K66K (Figure 4). 2015 Nucleic acids research Result HIV K65K;K66K 106;115 110;119 RT 59 61 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Infection with HIVTAM resulted in a 101-fold (single-cycle, P < 0.0001) and 61-fold (multiple-cycle, P < 0.0001) increase in indels at nucleotide 2742 compared to HIVWT, which was completely reversed by the presence of silent mutations at either K65K or K66K (Figure 5A and B, inset). 2015 Nucleic acids research Result HIV K65K;K66K 246;254 250;258 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Introduction of the TAM D67N in the HIV-1 RT of clade B isolates extends a homopolymeric run of A nucleotides from six to eight (Figure 4). 2015 Nucleic acids research Result HIV D67N 24 28 RT 42 44 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. K65K and K66K rescue increased frequency of indels caused by TAMs during single- and multiple-cycle infections. 2015 Nucleic acids research Result HIV K66K;K65K 9;0 13;4 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Moreover, introducing either K65K or K66K in this sequence disrupts the homopolymeric stretch (Figure 4), which alleviates RT pausing in vitro. 2015 Nucleic acids research Result HIV K65K;K66K 29;37 33;41 RT 123 125 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Our observation that the indel frequency increases at other, albeit less extensive, homopolymeric A regions in HIV-1 RT suggests that the increase in indels is likely a general phenomenon and not necessarily specific to the homopolymeric run introduced by D67N/K70R TAMs. 2015 Nucleic acids research Result HIV D67N;K70R 256;261 260;265 RT 117 119 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. RT silent mutations K65K or K66K alleviate a fitness defect conferred by the TAMs D67N/K70R. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 82;20;28;87 86;24;32;91 RT 0 2 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. RT silent mutations K65K or K66K do not potentiate resistance to RT inhibitors in the context of TAMs D67N/K70R. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 102;20;28;107 106;24;32;111 RT;RT 0;65 2;67 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Similar to the single-cycle infections, insertions detected for HIVTAMK65K_L (0.00985%) and HIVTAMK66K_L (0.03%) were comparable to HIVWT_L (0.09%) and were significantly lower (P < 0.0001 for both) than the frequency observed for HIVTAM_L (6.42%). 2015 Nucleic acids research Result HIV K65K;K66K 70;98 74;102 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Taken together, these data demonstrate that an increase in indel frequency but not SNV or MNV is associated with decreased fitness conferred by the TAMs D67N/K70R, and that silent mutations K65K or K66K completely reverse this indel formation. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 153;190;198;158 157;194;202;162 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Taken together, these data demonstrate that neither the K65K nor the K66K silent mutation potentiates drug resistance conferred by TAMs. 2015 Nucleic acids research Result HIV K65K;K66K 56;69 60;73 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Taken together, these data demonstrate that the emergence of the K65K or K66K silent mutations in the context of TAMs D67N/K70R in subtype B HIV-1 alleviates the fitness defect caused by these TAMs in the absence or presence of AZT and TFV. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 118;65;73;123 122;69;77;127 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Taken together, these data demonstrate that the TAMs D67N/K70R significantly increase the frequency of indel mutations at the homopolymeric region starting at nucleotide 2742, by up to 101-fold compared to WT, which is completely reversed by the presence of the silent mutations K65K or K66K. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 53;279;287;58 57;283;291;62 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. TAMs D67N/K70R in the absence or presence of silent mutations decrease the production of early and late RTn products. 2015 Nucleic acids research Result HIV D67N;K70R 5;10 9;14 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. TAMs including D67N and K70R are significantly associated with K65K or K66K, suggesting that these silent mutations contribute to strategies employed by the virus to escape from the inhibitory effects of antiretroviral drugs in vivo. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 15;63;71;24 19;67;75;28 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. The susceptibility of HIVTAMK65K and HIVTAMK66K was evaluated in the TZM-bl reporter cell line against the antiretroviral drugs, TFV and ZDV that target RT, in parallel with WT (HIVWT) and mutant virus carrying the TAMs D67N/K70R alone (HIVTAM; Table 1). 2015 Nucleic acids research Result HIV D67N;K70R 220;225 224;229 RT 153 155 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. These data show that the TAMs D67N/K70R decrease RTn efficiency. 2015 Nucleic acids research Result HIV D67N;K70R 30;35 34;39 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. We also observed an A to G change at nucleotide 2758 in HIVWT at a frequency of 3.2% resulting in the emergence of the K70R TAM (Figure 5C and Supplementary Table S2). 2015 Nucleic acids research Result HIV A2758G;K70R 20;119 52;123 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. We detected the G to A mutation at nucleotide position 2748 at a frequency of 2.4% for single-cycle infections (Figure 5C and Supplementary Table S2) resulting in the D67N substitution. 2015 Nucleic acids research Result HIV D67N;G2748A 167;16 171;59 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. We have previously reported that this substantial homopolymeric stretch causes the clade B HIV-1 RT to pause during DNA synthesis on RNA templates harboring D67N/K70R in cell-free assays. 2015 Nucleic acids research Result HIV D67N;K70R 157;162 161;166 RT 97 99 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. We next assessed whether the D67N/K70R TAMs confer an intracellular RTn defect, and whether this defect is reversed by K65K or K66K. 2015 Nucleic acids research Result HIV D67N;K65K;K66K;K70R 29;119;127;34 33;123;131;38 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. We observed a similar trend of identical SNV occurring at the same nucleotides resulting in the D67N (0.39% at nt 2748, P < 0.0001) and K70R (0.29% at nt 2758, P < 0.0001) in multiple-cycle infections (Figure 5D and Supplementary Table S3). 2015 Nucleic acids research Result HIV D67N;K70R 96;136 100;140 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. As with HIV-1, changes at integrase residues Y143, Q148 or N155, together with other secondary replacements in the integrase protein (i.e., E92Q, T97A, G140S, and possibly others), confer resistance to raltegravir in HIV-2. 2015 Retrovirology Result HIV E92Q;G140S;T97A 140;152;146 144;157;150 IN;IN 26;115 35;124 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Charpentier and colleagues reported that HIV-2ROD, HIV-1BRU, and eight HIV-2 isolates from INSTI-naive patients were comparably susceptible to dolutegravir in spreading infections of peripheral blood mononuclear cells (PBMC) (EC50 = 0.2-4 nM) and that three HIV-2 isolates from raltegravir-treated individuals with consensus integrase genotypes G140S + Q148R (group A), G140T + Q148R + N155H (group A), and T97A + Y143C (group H) were 63-, 9-, and 5-fold resistant to dolutegravir, respectively, in PBMC. 2015 Retrovirology Result HIV G140S;G140T;N155H;Q148R;Q148R;T97A;Y143C 345;370;386;353;378;407;414 350;375;391;358;383;411;419 IN;INSTI 325;91 334;96 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Despite repeated attempts using high multiplicities of infection (>=0.1) and prolonged incubation times (up to seven days), CEM-ss cultures inoculated with T97A + Y143C HIV-2ROD9 failed to produce detectable levels of infectious virus, indicating a severe fitness defect. 2015 Retrovirology Result HIV T97A;Y143C 156;163 160;168 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. For example, in the aforementioned study by Charpentier et al., a group H HIV-2 isolate with T97A + Y143C was only 5-fold resistant to dolutegravir (this isolate differs from HIV-2ROD9 at 24 of 293 amino acid sites in the integrase protein). 2015 Retrovirology Result HIV T97A;Y143C 93;100 97;105 IN 222 231 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. G140S + Q148R resulted in slight resistance to dolutegravir in HIV-1NL4-3 (3.5-fold; p <0.01, ANOVA), whereas E92Q + N155H and T97A + Y143C had no statistically significant effect in the HIV-1NL4-3 background (Figure 2D). 2015 Retrovirology Result HIV E92Q;N155H;Q148R;T97A;Y143C;G140S 110;117;8;127;134;0 114;122;13;131;139;5 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. In addition, the manufacturer of dolutegravir (ViiV Healthcare) reported that EC50 values against three clinical isolates of HIV-2 ranged from 0.09 nM to 0.61 nM in PBMC assays, and that combinations of substitutions A153G + N155H + S163G and E92Q + T97A + N155H + S163D in HIV-2 integrase conferred 4-fold decreases in dolutegravir susceptibility, while E92Q + N155H and G140S + Q148R resulted in 8.5-fold and 17-fold decreases, respectively. 2015 Retrovirology Result HIV A153G;E92Q;E92Q;G140S;N155H;N155H;N155H;Q148R;S163D;S163G;T97A 217;243;355;372;225;257;362;380;265;233;250 222;247;359;377;230;262;367;385;270;238;254 IN 280 289 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. In addition, the roles of novel INSTI-associated changes (i.e, H51Y, G118R, F121Y, E138A/K, and R263K) remain to be determined in HIV-2, and the level of dolutegravir resistance in vitro that correlates with virologic failure in HIV-2-infected patients is unknown. 2015 Retrovirology Result HIV E138A;E138K;F121Y;G118R;H51Y;R263K 83;83;76;69;63;96 90;90;81;74;67;101 INSTI 32 37 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. In contrast, HIV-2ROD9 mutants E92Q + N155H, G140S + Q148R, and T97A + Y143C were all resistant to dolutegravir (p < 0.0001, ANOVA) and showed EC50 values 4-, 21- and >5000-fold greater than those seen for equivalent mutants of HIV-1NL4-3, respectively (Figure 2D). 2015 Retrovirology Result HIV E92Q;G140S;N155H;Q148R;T97A;Y143C 31;45;38;53;64;71 35;50;43;58;68;76 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. In contrast, mutants E92Q, Y143C, E92Q + Y143C, Q148K, and Q148R were resistant to dolutegravir, with EC50 values 2.3-9.3-fold greater than that of the parental strain (Figure 2A), and variants E92Q + N155H, T97A + N155H and G140S + Q148R exhibited 11-33-fold resistance to the drug (p < 0.05, ANOVA; Figure 2A and B). 2015 Retrovirology Result HIV E92Q;E92Q;E92Q;G140S;N155H;N155H;Q148K;Q148R;Q148R;T97A;Y143C;Y143C 21;34;194;225;201;215;48;59;233;208;27;41 25;38;198;230;206;220;53;64;238;212;32;46 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. In experiments with T97A + Y143C HIV-2ROD9, dolutegravir concentrations as high as 10 muM failed to reduce viral replication by 50% (Figure 2A and C; EC50 > 10 muM), although modest dose-dependent inhibition was apparent at doses >=100 nM (Figure 2C). 2015 Retrovirology Result HIV T97A;Y143C 20;27 24;32 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. In the VIKING-3 trial, dolutegravir response rates (<50 HIV-1 RNA copies/ml at week 24) declined from 79% (n = 100/126) for patients without Q148 mutations at baseline (including those with N155H, Y143C/H/R, T66A, E92Q, or historical evidence of INSTI resistance), to 58% (21/36) for patients with Q148 plus one additional secondary mutation, to 24% (5/21) for those with Q148 plus two or more secondary mutations. 2015 Retrovirology Result HIV E92Q;N155H;T66A;Y143C;Y143H;Y143R 214;190;208;197;197;197 218;195;212;206;206;206 INSTI 246 251 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Lastly, we performed a head-to-head comparison of the phenotypes conferred by E92Q + N155H, G140S + Q148R, and T97A + Y143C in HIV-1NL4-3 and HIV-2ROD9 in the single-cycle assay. 2015 Retrovirology Result HIV E92Q;G140S;N155H;Q148R;T97A;Y143C 78;92;85;100;111;118 82;97;90;105;115;123 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Our analysis shows that equivalent amino acid changes in the integrase proteins of HIV-1 and HIV-2 can have differing effects on dolutegravir susceptibility (Figure 2D) and that, in HIV-2ROD9, integrase changes Q148K, T97A + Y143C, E92Q + N155H, T97A + N155H, and G140S + Q148R confer moderate to high levels of dolutegravir resistance (>=10-fold; Figure 2A-C and Table 1). 2015 Retrovirology Result HIV E92Q;G140S;N155H;N155H;Q148K;Q148R;T97A;T97A;Y143C 232;264;239;253;211;272;218;246;225 236;269;244;258;216;277;222;250;230 IN;IN 61;193 70;202 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Single amino acid changes T97A, G140S, Q148H and N155H had no significant effect on dolutegravir sensitivity (p > 0.05, ANOVA; Figure 2A). 2015 Retrovirology Result HIV G140S;N155H;Q148H;T97A 32;49;39;26 37;54;44;30 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. The ability of dolutegravir to inhibit strains resistant to other INSTI is of particular importance-in HIV-1, mutations Q148H/K/R, together with secondary changes in the integrase protein, confer resistance to dolutegravir in cell culture, and other mutations associated with diminished in vitro susceptibility to dolutegravir have been reported. 2015 Retrovirology Result HIV Q148H;Q148K;Q148R 120;120;120 129;129;129 IN;INSTI 170;66 179;71 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. The resultant EC50 values for the parental strain, E92Q + N115H, and G140S + Q148R were 0.24, 2.1 and 73 nM, respectively, indicating 8.8-fold resistance to dolutegravir for E92Q + N115H and 300-fold resistance for G140S + Q148R. 2015 Retrovirology Result HIV E92Q;E92Q;G140S;G140S;N115H;N115H;Q148R;Q148R 51;174;69;215;58;181;77;223 55;178;74;220;63;186;82;228 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. This result is consistent with the poor replication capacity previously reported for T97A + Y143C HIV-2ROD9. 2015 Retrovirology Result HIV T97A;Y143C 85;92 89;97 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. We also evaluated the dolutegravir sensitivities of E92Q + N155H, T97A + Y143C, and G140S + Q148R HIV-2ROD9 in three-day spreading infections of immortalized T cells (CEM-ss). 2015 Retrovirology Result HIV E92Q;G140S;N155H;Q148R;T97A;Y143C 52;84;59;92;66;73 56;89;64;97;70;78 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. 10 to 15%, and the combination of S345T with E350K (mt2c) almost doubled the excision efficiency (ca. 2015 Retrovirology Result HIV E350K;S345T 45;34 50;39 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Accordingly, mt2a and mt2b, also harboring the K211I substitution, were less efficient in initiating polymerization than mt2c. 2015 Retrovirology Result HIV K211I 47 52 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Additionally, all PR-RT enzymes used, carry a mutation in the PR domain leading to the active site residue exchange D24A. 2015 Retrovirology Result HIV D24A 116 120 PR;PR;RT 18;62;21 20;64;23 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Although all proteins were able to extend the primer by a few nucleotides, K211I appeared to be the least active enzyme among the single exchange variants. 2015 Retrovirology Result HIV K211I 75 80 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Among the enzyme variants carrying two substitutions, a combination of the key exchange S345T with K211I (mt2a) improved the excision efficiency as compared to S345T alone from ca. 2015 Retrovirology Result HIV K211I;S345T;S345T 99;88;160 104;93;165 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Due to a decreased binding affinity for all dNTPs in enzymes harboring K211I, dissociation of the incorrect nucleotide and thereby correct base pairing is facilitated. 2015 Retrovirology Result HIV K211I 71 76 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. E350K and mt2c reach higher vmax/KM-values than the WT, indicating higher catalytic activities (Table 2). 2015 Retrovirology Result HIV E350K 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Even at a 59-fold excess of ATP no chemical shift changes were detectable in the spectrum of RTshort-mt4-T345S. 2015 Retrovirology Result HIV T345S 105 110 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Furthermore, substitution E350K and I224T appear to compensate the polymerization deficiency of K211I in the mt3 variant as well as in the highly resistant mt4 protein. 2015 Retrovirology Result HIV E350K;I224T;K211I 26;36;96 31;41;101 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. However, in mt3 the presence of K211I supported AZTMP removal. 2015 Retrovirology Result HIV K211I 32 37 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. However, in order to restore viral fitness completely, the additional exchange I224T, resulting in mt4, is required. 2015 Retrovirology Result HIV I224T 79 84 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. However, the polymerization behavior of mt4 is again comparable to the WT owing to the presence of the polymorphism I224T. 2015 Retrovirology Result HIV I224T 116 121 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. However, this effect was obliterated by the introduction of K211I. 2015 Retrovirology Result HIV K211I 60 65 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. However, this substitution leads to an impaired polymerization reaction, which can be recovered in mt4 by I224T. 2015 Retrovirology Result HIV I224T 106 111 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In contrast to HIV-1 RT, AZT resistance substitutions in SFVmac PR-RT do not result in an aromatic amino acid, but instead make an already existent Trp accessible to fulfill a similar task as the T215Y/F exchange in HIV-1 RT. 2015 Retrovirology Result HIV T215F;T215Y 196;196 203;203 PR;RT;RT;RT 64;21;67;222 66;23;69;224 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In contrast, mt2b, lacking the S345T substitution, exhibited no significant AZTMP removal activity. 2015 Retrovirology Result HIV S345T 31 36 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In contrast, mt2c lacking K211I exhibits high polymerization activity. 2015 Retrovirology Result HIV K211I 26 31 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In mt3 the reduced viral fitness of K211I is improved by S345T and E350K (Table 1), whereas the impaired fidelity caused by S345T and E350K is counteracted by K211I (Figure 4C). 2015 Retrovirology Result HIV E350K;E350K;K211I;K211I;S345T;S345T 67;134;36;159;57;124 72;139;41;164;62;129 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In mt3, S345T and E350K appear to compensate the effect of K211I, since mt3, although containing the K211I exchange exhibited WT fidelity. 2015 Retrovirology Result HIV E350K;K211I;K211I;S345T 18;59;101;8 23;64;106;13 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In the highly AZT resistant SFVmac PR-RT the substitution S345T might alter the surface exposed residues in its vicinity and thus makes a Trp residue more accessible for hydrophobic interactions with ATP. 2015 Retrovirology Result HIV S345T 58 63 PR;RT 35;38 37;40 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Interestingly, due to the presence of K211I, the activity of mt3 is reduced as compared to the WT. 2015 Retrovirology Result HIV K211I 38 43 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. K211I is part of a loop in the fingers subdomain, homologous to the beta beta3-beta4 loop in HIV-1 RT. 2015 Retrovirology Result HIV K211I 0 5 RT 99 101 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. KM-values of K211I and variants harboring K211I (mt2b and mt2a) were about 3-fold (mt2b) or 5-fold (mt2a) higher than that of the WT enzyme. 2015 Retrovirology Result HIV K211I;K211I 13;42 18;47 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Moreover, the high excision activity was retained with mt4, confirming that I224T improves viral fitness in the fully resistant virus but is not involved in AZT resistance per se. 2015 Retrovirology Result HIV I224T 76 81 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. mt2c, lacking the K211I substitution, showed a behavior similar to the WT enzyme (Figure 4C, Additional file 1: Table S1). 2015 Retrovirology Result HIV K211I 18 23 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Obviously, the K211I exchange on its own and in mt2a yields replication deficient virus (Figure 2B, Table 1). 2015 Retrovirology Result HIV K211I 15 20 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Obviously, the K211I exchange results in severely reduced polymerization activity since the single as well as the double variants harboring K211I (mt2a, mt2b) are impaired. 2015 Retrovirology Result HIV K211I;K211I 15;140 20;145 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Obviously, this Trp residue is obscured in RTshort-WT as well as in RTshort-mt4-T345S. 2015 Retrovirology Result HIV T345S 80 85 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Quantification of the extended primer after misincorporation disclosed that variant K211I, as well as mt2a and mt2b, also harboring the K211I exchange, exhibited a significantly higher fidelity than the other enzymes. 2015 Retrovirology Result HIV K211I;K211I 84;136 89;141 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Rather, quantification of the cleavage products indicated that E350K exhibits a significantly higher RNase H activity than all the other enzymes. 2015 Retrovirology Result HIV E350K 63 68 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Remarkably, the specific polymerization activity of E350K is significantly higher than that of the WT. 2015 Retrovirology Result HIV E350K 52 57 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. S345T, showed significant (>5%) AZTMP excision activity. 2015 Retrovirology Result HIV S345T 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Since S345T is the only single amino acid exchange exhibiting AZTMP excision activity (Figure 2C), we reversed the S345T exchange in RTshort-mt4 back to WT (=RTshort-mt4-T345S) and recorded 1H/15N-HSQC spectra in the absence and presence of ATP (Figure 5C). 2015 Retrovirology Result HIV S345T;S345T;T345S 6;115;170 11;120;175 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Since the specific activities of the variants containing K211I were considerably lower than the WT activities, we performed primer extension assays with a 30/50mer DNA/DNA (P30/T50) substrate which was 5' 32P endlabeled at the primer. 2015 Retrovirology Result HIV K211I 57 62 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Taken together, these data show that the single substitution S345T results in moderate ATZMP excision activity, which can be further improved in combination with K211I or E350K. 2015 Retrovirology Result HIV E350K;K211I;S345T 171;162;61 176;167;66 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. The combination of K211I and E350K (mt2b) showed little AZTMP excision in vitro. 2015 Retrovirology Result HIV E350K;K211I 29;19 34;24 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. The I224T exchange in mt4 is probably a polymorphism and does not contribute substantially to AZT-resistance but to viral fitness. 2015 Retrovirology Result HIV I224T 4 9 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. The major gain in AZTMP excision efficiency is due to the additional exchange K211I. 2015 Retrovirology Result HIV K211I 78 83 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. The model shows that the polymorphism I224T is located at some distance to the active site residues YVDD, while S345T and E350K are positioned in the palm subdomain next to the active site and thus could be involved in ATP-binding. 2015 Retrovirology Result HIV E350K;I224T;S345T 122;38;112 127;43;117 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. The reduced polymerization activity of variant K211I might be due to changes in affinities for the nucleic acid substrate and/or the dNTP. 2015 Retrovirology Result HIV K211I 47 52 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Therefore, we investigated whether K211I, which is also positioned in the fingers subdomain, alters the SFVmac PR-RT's fidelity. 2015 Retrovirology Result HIV K211I 35 40 PR;RT 111;114 113;116 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. These data imply that E350K might be the second AZT resistance mutation, since the combination of the putative first exchange S345T with K211I leads to replication deficient virus (Table 1). 2015 Retrovirology Result HIV E350K;K211I;S345T 22;137;126 27;142;131 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. These findings confirm that K211I leads to an impairment of polymerization activity due to a decrease in nucleotide binding affinity, but not by altering the P/T binding affinity. 2015 Retrovirology Result HIV K211I 28 33 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. This indicates that S345T is the key amino acid exchange for AZTMP removal. 2015 Retrovirology Result HIV S345T 20 25 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. This is similar to the results shown with the substitutions K65R and M184V/I in HIV-1 RT revealing an inverse correlation between fidelity and processivity or activity of the RT. 2015 Retrovirology Result HIV K65R;M184I;M184V 60;69;69 64;76;76 RT;RT 86;175 88;177 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. This result indicates a key role of the S345T substitution in AZT resistance via creating an ATP binding pocket, which is necessary for the excision mechanism. 2015 Retrovirology Result HIV S345T 40 45 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. This was also illustrated by the fact that the dramatic decrease of viral titer with the mt3 virus (8.6% of the WT virus) in the absence of AZT was fully compensated by I224T in the mt4 virus, bringing the titer back to WT levels (ca. 2015 Retrovirology Result HIV I224T 169 174 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. To further assess the effect of the K211I substitution on AZT resistance, we determined the kinetic parameters of the enzymes (Table 2). 2015 Retrovirology Result HIV K211I 36 41 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. To overcome the reduced nucleotide binding affinity caused by K211I, a 5-fold higher nucleotide concentration than in the polymerization assay was used for all enzymes. 2015 Retrovirology Result HIV K211I 62 67 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. We have shown previously that the purified SFVmac PR-RTs mt3 (K211I, S345K, E350K) and mt4 (K211I, I224T, S345K, E350K) are able to excise AZTMP with similar efficiency from an AZTMP-terminated primer in the presence of ATP. 2015 Retrovirology Result HIV E350K;E350K;I224T;K211I;K211I;S345K;S345K 76;113;99;62;92;69;106 81;118;104;67;97;74;111 PR;RT 50;53 52;56 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. We have shown previously that the single amino acid exchange S345T leads to moderate drug resistance of the virus in the presence of 0.5 - 5 muM AZT. 2015 Retrovirology Result HIV S345T 61 66 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. While KM-values for S345T, mt2a and mt2c were comparable, significantly lower KM-values were measured with mt3 and mt4, again indicating that the combination of the three exchanges K211I, S345T and E350K is necessary for high affinity ATP binding and thus for efficient AZTMP removal. 2015 Retrovirology Result HIV E350K;K211I;S345T;S345T 198;181;20;188 203;186;25;193 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. Despite distinct selection pressure at position 1 of RM9-Nef by HLA-B*07:02 (R71K) (Figure 2F) (Table 1), peptide residue Arg1 was in a similar conformation in all 4 HLAIs (Figure 4A). 2015 Retrovirology Result HIV R71K 77 81 Nef 57 60 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. HLA-B*07:02 expressing individuals exhibited strong selection at P1 in the epitope (R71K: 41%, P = 7x10-5), whereas HLA-B*81:01 expressing individuals showed selection of variants at P6 of the epitope (L76V/T/I, L76X, P = 2x10-43) with no selection mediated by HLA-B*42:01 and HLA-B*42:02 on this RM9-Nef epitope (Figure 2F) (Table 1). 2015 Retrovirology Result HIV L76I;L76T;L76V;R71K 202;202;202;84 210;210;210;88 Nef;Gag 301;183 304;185 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. Of note, selection for the above-mentioned T186S at position 7 of the TL9-p24 epitope (31%, P = 2x10-24) was only significant in HLA-B*81:01-positive individuals. 2015 Retrovirology Result HIV T186S 43 48 p24 74 77 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. The larger side chains of Arg156 and Gln152 in HLA-B*07:02 pushed Leu6 up compared to the smaller side chains of Leu156 and Val152 in HLA-B*81:01 (Figure 4C), changes which may be linked to the L76V/T/I selection that is mediated only by HLA-B*81:01. 2015 Retrovirology Result HIV L76I;L76T;L76V 194;194;194 202;202;202 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Etravirine and rilpivirine resistance was usually caused by Y181C, a mutation selected primarily by nevirapine. 2015 PLoS medicine Result HIV Y181C 60 65 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. F53Y accounted for a higher proportion of PI SDRMs in subtype CRF02_AG compared with pooled viruses belonging to the remaining subtypes (11% versus 1%; four of 37 versus seven of 1,281; p < 0.001). 2015 PLoS medicine Result HIV F53Y 0 4 PI 42 44 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. However, among the 48,722 samples without NNRTI SDRMs, 5.6% (644 of 11,536) of samples in SSA, 1.6% (104 of 6,522) in SSEA, and 2.6% (655 of 25,035) in the pooled upper-income countries were predicted to have low-level rilpivirine resistance as a result of the polymorphic mutation E138A, which occurs in up to 6% of subtype A and C viruses. 2015 PLoS medicine Result HIV E138A 282 287 NNRTI 42 47 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. In addition to the large Japanese cluster of PI SDRM M46I (30 individuals), there was one SDRM cluster of viruses from five individuals in North America with this mutation. 2015 PLoS medicine Result HIV M46I 53 57 PI 45 47 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. In all regions, the proportion of PI-treated individuals with M46L or I85V divided by the number of ARV-naive individuals with these SDRMs was much lower than the same proportion for all other commonly occurring SDRMs. 2015 PLoS medicine Result HIV I85V;M46L 70;62 74;66 PI 34 36 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. In FSU countries, there was one SDRM cluster of six viruses with the PI SDRM L23I, a nelfinavir-resistance mutation. 2015 PLoS medicine Result HIV L23I 77 81 PI 69 71 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. In Latin America/Caribbean, one study contained an SDRM cluster of three viruses with the NNRTI SDRM K103N. 2015 PLoS medicine Result HIV K103N 101 106 NNRTI 90 95 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. In these three regions, the NNRTI SDRM K103N alone occurred in 22 clusters (96 individuals), a NRTI SDRM T215 revertant alone occurred in 16 clusters (82 individuals), and the NNRTI SDRM G190A alone occurred in five clusters (17 individuals). 2015 PLoS medicine Result HIV G190A;K103N 187;39 192;44 NNRTI;NNRTI;NRTI 28;176;95 33;181;99 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. K103N accounted for a higher proportion of NNRTI SDRMs in subtype B viruses compared with pooled viruses belonging to the remaining subtypes (53% versus 40%; 646 of 1,212 versus 214 of 534; p < 0.001). 2015 PLoS medicine Result HIV K103N 0 5 NNRTI 43 48 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. K103N was the most common NNRTI SDRM in each region except for SSEA, accounting for 45% (137) of 306 NNRTI SDRMs in SSA, 49% (164) of 205 NNRTI SDRMs in Latin America/Caribbean, and 54% (612) of 1,140 NNRTI SDRMs in the pooled upper-income countries (S5 Table). 2015 PLoS medicine Result HIV K103N 0 5 NNRTI;NNRTI;NNRTI;NNRTI 26;101;138;201 31;106;143;206 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. K70E (2.7%; eight of 298) accounted for a higher proportion of the NRTI SDRMs in SSA than in other regions (<0.3% in each of the other regions; p < 0.001). 2015 PLoS medicine Result HIV K70E 0 4 NRTI 67 71 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. L74I (4.4%; eight of 184), V75M (8.2%; 15 of 184), and M184I (3.8%; seven of 184) accounted for a higher proportion of the NRTI SDRMs in SSEA than in other regions (<2% for each mutation in each of the other regions; p < 0.001). 2015 PLoS medicine Result HIV M184I;V75M;L74I 55;27;0 60;31;4 NRTI 123 127 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. M184V and the TAMs were the most common NRTI SDRMs in all four regions (S4 Table). 2015 PLoS medicine Result HIV M184V 0 5 NRTI 40 44 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. M46I was disproportionately more common in SSEA, where it accounted for 33% (26) of 79 PI SDRMs, compared with SSA (14%; 16 of 117; p < 0.001), Latin America/Caribbean (12%; 19 of 156; p < 0.001), and the pooled upper-income countries (16%, 159 of 795; p < 0.001). 2015 PLoS medicine Result HIV M46I 0 4 PI 87 89 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. M46I, which was significantly more common in individuals from SSEA, was not significantly associated with any subtype. 2015 PLoS medicine Result HIV M46I 0 4 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. M46I/L, I85V, and L90M were the four most common PI SDRMs in SSA and SSEA, and among the six most common SDRMs in all regions. 2015 PLoS medicine Result HIV I85V;L90M;M46L;M46I 8;18;0;0 12;22;6;6 PI 49 51 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. M46L was not associated with a region, accounting for 21% (24 of 117), 18% (14 of 79), 10% (16 of 156), and 12% (114 of 986) of PI SDRMs in SSA, SSEA, Latin America/Caribbean, and the pooled upper-income countries, respectively (S6 Table). 2015 PLoS medicine Result HIV M46L 0 4 PI 128 130 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Nevirapine and efavirenz resistance were predicted in about 1% and 0.5% of virus samples without NNRTI SDRMs as a result of several minimally polymorphic (e.g., A98G, V108I, and V179D) and rare nonpolymorphic (e.g., E138K, G190Q, F227C, and K238T) NNRTI-resistance mutations. 2015 PLoS medicine Result HIV A98G;E138K;F227C;G190Q;K238T;V108I;V179D 161;216;230;223;241;167;178 165;221;235;228;246;172;183 NNRTI;NNRTI 97;248 102;253 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Of the 19 NNRTI SDRMs, four mutations:K101E, K103N, Y181C, and G190A:occurred in >=0.1% of the 50,870 viruses from all regions. 2015 PLoS medicine Result HIV G190A;K101E;K103N;Y181C 63;38;45;52 68;43;50;57 NNRTI 10 15 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Of the 19 NNRTI SDRMs, Y181C accounted for a higher proportion of NNRTI SDRMs in CRF01_AE viruses compared with pooled viruses belonging to the remaining subtypes (33% versus 13%; 38 of 115 versus 212 of 1,631; p < 0.001) (S8 Table). 2015 PLoS medicine Result HIV Y181C 23 28 NNRTI;NNRTI 10;66 15;71 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Of the 34 NRTI SDRMs, 16 occurred in >=0.1% of the 50,870 viruses from all regions: most commonly M184V, the TAMs (M41L, D67G/N, K70R, L210W, T215F/Y, K219E/Q), the T215 revertants (T215C/D/E/S), T69D, and F77L. 2015 PLoS medicine Result HIV D67G;D67N;F77L;K219E;K219Q;K70R;L210W;M184V;M41L;T215C;T215D;T215E;T215F;T215S;T215Y;T69D 121;121;206;151;151;129;135;98;115;182;182;182;142;182;142;196 127;127;210;158;158;133;140;103;119;193;193;193;149;193;149;200 NRTI 10 14 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Of the 40 PI SDRMs, L23I (16%; eight of 51) accounted for a higher proportion of PI SDRMs in subtype A viruses compared with pooled viruses belonging to the remaining subtypes (1%; 11 of 1,267; p < 0.001) (S9 Table). 2015 PLoS medicine Result HIV L23I 20 24 PI;PI 10;81 12;83 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Of the eight subtype A viruses with L23I, six were part of a cluster of six sequences from one FSU study. 2015 PLoS medicine Result HIV L23I 36 40 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. P225H accounted for a higher proportion of NNRTI SDRMs in CRF02_AG viruses compared with pooled viruses belonging to the remaining subtypes (14% versus 3%; nine of 65 versus 48 of 1,681; p < 0.001). 2015 PLoS medicine Result HIV P225H 0 5 NNRTI 43 48 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Predicted lamivudine resistance was usually high-level, caused by M184V/I. 2015 PLoS medicine Result HIV M184I;M184V 66;66 73;73 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. The 17 individuals with M46I in SSEA included 11 subtype CRF01_AE, four subtype C, and two subtype B viruses. 2015 PLoS medicine Result HIV M46I 24 28 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. The temporal increase in the odds of PI-associated TDR in this region was partly attributable to two extended lineages in Japan published in two studies, one containing 30 individuals with viruses containing M46I alone and another containing 16 individuals with viruses containing M46L alone (S1 and S2 Figs). 2015 PLoS medicine Result HIV M46I;M46L 208;281 212;285 PI 37 39 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. V106M accounted for a higher proportion of genotypic NNRTI SDRMs in subtype C viruses than in pooled viruses belonging to the remaining subtypes (5% versus 1%; eight of 179 versus ten of 1,567; p < 0.001). 2015 PLoS medicine Result HIV V106M 0 5 NNRTI 53 58 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. V75M accounted for a higher proportion of NRTI SDRMs in CRF01_AE viruses compared with pooled viruses belonging to the remaining subtypes (10% versus 1%; 16 of 157 versus 25 of 3,397; p < 0.001). 2015 PLoS medicine Result HIV V75M 0 4 NRTI 42 46 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. Y181C was the most common NNRTI SDRM in SSEA, accounting for 32% (44) of 136 NNRTI SDRMs in this region. 2015 PLoS medicine Result HIV Y181C 0 5 NNRTI;NNRTI 26;77 31;82 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. A neutralizing MAb directed against the gp41 membrane-proximal external region (MPER), 4E10, exhibited a reduction in recognition of the I559P mutant relative to that of the wt Env. 2015 PloS one Result HIV I559P 137 142 gp41;Env 40;177 44;180 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Although b12 binding to the SOSIP Env was better than that of the I559P Env, VRC01 binding to the SOSIP mutant was significantly decreased compared with wt Env. 2015 PloS one Result HIV I559P 66 71 Env;Env;Env 34;72;156 37;75;159 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Apparently, the I559P and SOS changes can alter Env quaternary structure so that MAb binding to the CD4-binding site of gp120 is affected. 2015 PloS one Result HIV I559P 16 21 gp120;Env 120;48 125;51 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Apparently, the SOS change results in a greater propensity to form and expose the 17b epitope on gp120, which can compensate for the negative effects of the I559P alteration on 17b binding. 2015 PloS one Result HIV I559P 157 162 gp120 97 102 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. As shown in Fig 9, the introduction of the I559P change into the full-length gp160 Env closely recapitulated the profound conformational effects described above for Envs lacking the cytoplasmic tail. 2015 PloS one Result HIV I559P 43 48 gp160;Env;Env 77;83;165 82;86;169 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Because the structure of the gp120 core in the soluble gp140 SOSIP.664 Env crystals unexpectedly resembles the CD4-bound conformation, we also studied the S375W mutant, in which the aromatic ring of a tryptophan residue fills the Phe43 cavity of the gp120 core; in other HIV-1 strains, this mutant is predisposed to assume the CD4-bound conformation. 2015 PloS one Result HIV S375W 155 160 gp120;gp120;gp140;Env 29;250;55;71 34;255;60;74 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. By contrast, similar to the results with the I559P mutant, A32 binding to SOSIP Env in the absence or presence of sCD4 was significantly lower than that of the wt Env. 2015 PloS one Result HIV I559P 45 50 Env;Env 80;163 83;166 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. By contrast, the 19b and GE2 JG8 anti-V3 MAbs bound the I559P variant less efficiently than the wt Env (Fig 7 and Table 2); similar results were also obtained with the 447 D52 and 2191 anti-V3 MAbs (data not shown). 2015 PloS one Result HIV I559P 56 61 Env 99 102 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Compared with the wt full-length Env, the I559P mutant was recognized less efficiently by the neutralizing MAb, PGT151, by the F240 anti-gp41 MAb, and by sera from HIV-1-infected individuals. 2015 PloS one Result HIV I559P 42 47 gp41;Env 137;33 141;36 HIV infections 164 178 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Consistent with this explanation, recognition of the I559P and SOSIP Envs by the PG9 MAb, which recognizes gp120 V2 region glycans in a manner that is sensitive to quaternary trimer conformation, was slightly lower than that of the wt Env (Table 2 and Fig 6). 2015 PloS one Result HIV I559P 53 58 gp120;Env;Env 107;69;235 112;73;238 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Decreased binding of b12 to the I559P mutant Env from HIV-1JR-FL has been previously noted. 2015 PloS one Result HIV I559P 32 37 Env 45 48 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Effect of I559P on the capacity of the SOS variant to mediate membrane fusion under reducing conditions. 2015 PloS one Result HIV I559P 10 15 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Effect of the I559P and S375W changes on the function, processing and subunit association of the HIV-1BG505 Envs. 2015 PloS one Result HIV I559P;S375W 14;24 19;29 Env 108 112 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. If the unliganded HIV-1BG505 Env assumes the gp120 core conformation seen in the soluble gp140 SOSIP.664 crystal structure, the S375W mutant should exhibit phenotypes close to those of the wt HIV-1BG505 Env. 2015 PloS one Result HIV S375W 128 133 gp120;gp140;Env;Env 45;89;29;203 50;94;32;206 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. In contrast, regardless of the concentration of DTT in the medium, the I559P and SOSIP mutants failed to support virus entry or cell-cell fusion. 2015 PloS one Result HIV I559P 71 76 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. In fact, the recognition of the SOS mutant by the Cluster I MAbs was lower than that of the A501C and T605C single-cysteine substitution mutants (data not shown), suggesting that both cysteines may need to form a disulfide bond to cause the observed reduction in recognition of the SOS mutant. 2015 PloS one Result HIV A501C;T605C 92;102 97;107 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. In the presence of sCD4, the I559P and SOSIP Envs exhibited a higher-than-wt level of 35O22 MAb binding. 2015 PloS one Result HIV I559P 29 34 Env 45 49 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. In this study, the phenotypes of the I559P mutant were evaluated in the background of the wild-type (wt) HIV-1BG505 Env and in an Env with the SOS cysteine substitutions. 2015 PloS one Result HIV I559P 37 42 Env;Env 116;130 119;133 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Indeed, the I559P change resulted in decreased full-length Env recognition by the CD4BS MAbs, VRC01 and b12. 2015 PloS one Result HIV I559P 12 17 Env 59 62 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Likewise, the I559P, SOS and SOSIP Envs did not detectably mediate cell-cell fusion, whereas the wt and S375W Envs efficiently promoted syncytium formation (Figs 1A, 3B and Table 1). 2015 PloS one Result HIV I559P;S375W 14;104 19;109 Env;Env 35;110 39;114 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. MAbs against gp41 Cluster I and Cluster II epitopes exhibited much lower binding to the I559P mutant compared with the wt Env. 2015 PloS one Result HIV I559P 88 93 gp41;Env 13;122 17;125 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Recombinant luciferase-expressing HIV-1 viruses bearing the full-length wt, I559P or S375W mutant Envs were spinoculated onto Cf2Th cells expressing human CD4 and CCR5 to assess the ability of the Envs to support virus entry. 2015 PloS one Result HIV I559P;S375W 76;85 81;90 Env;Env 98;197 102;201 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Remarkably, the I559P and SOSIP Envs were recognized less efficiently than the wt and S375W Envs by sera from several HIV-1-infected individuals (Table 2 and Fig 5). 2015 PloS one Result HIV I559P;S375W 16;86 21;91 Env;Env 32;92 36;96 HIV infections 118 132 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Similar phenotypes were observed for an I559P mutant Env with a truncated gp41 cytoplasmic tail (Table 1). 2015 PloS one Result HIV I559P 40 45 gp41;Env 74;53 78;56 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The 35O22 MAb bound better to the S375W and SOSIP Envs than to the wt Env in the absence of sCD4. 2015 PloS one Result HIV S375W 34 39 Env;Env 50;70 54;73 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The binding of PGT151 to the S375W, I559P and SOSIP Env mutants was reduced, relative to that of the wt and SOS Envs. 2015 PloS one Result HIV I559P;S375W 36;29 41;34 Env;Env 52;112 55;116 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The binding of sCD4 partially restored 17b binding to the I559P Env, but A32 binding to the I559P mutant was significantly decreased compared to wt Env, even in the presence of sCD4. 2015 PloS one Result HIV I559P;I559P 58;92 63;97 Env;Env 64;148 67;151 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The expression, processing and subunit association of the I559P and S375W Env variants were studied by transfection of 293T cells with pcDNA3.1 plasmids expressing the full-length wild-type (wt) and mutant HIV-1BG505 Envs, as described. 2015 PloS one Result HIV I559P;S375W 58;68 63;73 Env;Env 74;217 77;221 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P alteration likewise eliminated the ability of an HIV-1BG505 Env with a truncated gp41 cytoplasmic tail to mediate virus infection and syncytium formation (Table 1). 2015 PloS one Result HIV I559P 4 9 gp41;Env 91;70 95;73 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P change significantly compromises the function of the HIV-1BG505 Env, and this infectivity defect is not compensated by the SOS cysteine substitutions. 2015 PloS one Result HIV I559P 4 9 Env 74 77 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P Env also failed to mediate the formation of syncytia, whereas the S375W mediated cell-cell fusion, although less efficiently than the wt Env (Fig 1A). 2015 PloS one Result HIV I559P;S375W 4;76 9;81 Env;Env 10;147 13;150 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The PGT121 neutralizing MAb, which recognizes a carbohydrate-dependent epitope in the gp120 V3 region, bound the I559P and SOSIP mutants better than the wt Env (Table 2). 2015 PloS one Result HIV I559P 113 118 gp120;Env 86;156 91;159 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The proteolytic processing of the I559P and S375W Env precursors was modestly decreased, compared with that of the wt Env (Fig 1B). 2015 PloS one Result HIV I559P;S375W 34;44 39;49 Env;Env 50;118 53;121 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The recognition of the HIV-1BG505 Env variants (wt, S375W, I559P, SOS and SOSIP) by monoclonal antibodies (MAbs) and other ligands was measured by cell-surface ELISA. 2015 PloS one Result HIV I559P;S375W 59;52 64;57 Env 34 37 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The recognition of the I559P Env by the CD4-binding site (CD4BS) MAbs, VRC01 and b12, was decreased relative to that of the wt Env. 2015 PloS one Result HIV I559P 23 28 Env;Env 29;127 32;130 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The relative binding of these MAbs to the SOSIP mutant was also low, indicating that the SOS alteration does not compensate for the I559P change in this instance. 2015 PloS one Result HIV I559P 132 137 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The S375W and SOS Envs bound CD4-Ig efficiently, but the binding of CD4-Ig to the I559P mutant was relatively decreased (Fig 5 and Table 2). 2015 PloS one Result HIV I559P;S375W 82;4 87;9 Env 18 22 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The S375W virus was more sensitive than the wt virus to sCD4, whereas both viruses were neutralized equivalently by VRC01 (Fig 2A and 2B). 2015 PloS one Result HIV S375W 4 9 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The sensitivity of the wt and S375W viruses to neutralization by soluble CD4 (sCD4) and by the VRC01 and 17b monoclonal antibodies (MAbs) was examined. 2015 PloS one Result HIV S375W 30 35 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The spontaneous and sCD4-induced binding of the 17b and A32 MAbs, which recognize distinct CD4-induced (CD4i) gp120 epitopes, to the S375W mutant was increased, relative to that observed for wt Env (Fig 4 and Table 2). 2015 PloS one Result HIV S375W 133 138 gp120;Env 110;194 115;197 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The spontaneous recognition of the I559P mutant by the 17b and A32 MAbs was dramatically reduced, compared with that of the wt Env (Fig 4 and Table 2). 2015 PloS one Result HIV I559P 35 40 Env 127 130 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The viruses with the wt and S375W Envs infected the Cf2Th-CD4/CCR5 cells, but the viruses with the I559P, SOS and SOSIP Envs did not infect the cells (Fig 3A and data not shown). 2015 PloS one Result HIV I559P;S375W 99;28 104;33 Env;Env 34;120 38;124 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The viruses with the wt and S375W Envs infected the CfTh-CD4/CCR5 cells, but the viruses with the I559P Envs did not support infection (data not shown). 2015 PloS one Result HIV I559P;S375W 98;28 103;33 Env;Env 34;104 38;108 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The wt and S375W Envs exhibited similar levels of gp120-gp41 association; the association of the gp120 subunit with the I559P Env trimer was significantly increased, relative to that seen for the wt Env (Fig 1C). 2015 PloS one Result HIV I559P;S375W 120;11 125;16 gp120;gp120;gp41;Env;Env;Env 50;97;56;17;126;199 55;102;60;21;129;202 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. These results further suggest that the I559P change in gp41 alters the gp120 conformation in the Env trimer. 2015 PloS one Result HIV I559P 39 44 gp120;gp41;Env 71;55;97 76;59;100 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. These results indicate that the I559P change completely compromises the function of the HIV-1BG505 Env. 2015 PloS one Result HIV I559P 32 37 Env 99 102 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. These results suggest that the S375W, I559P and SOSIP changes lead to alterations in the relationship between the gp120 and gp41 subunits of the Env trimer. 2015 PloS one Result HIV I559P;S375W 38;31 43;36 gp120;gp41;Env 114;124;145 119;128;148 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. These results suggest that the sampling of the CD4-bound conformation by the gp120 subunit is reduced by the I559P change in gp41. 2015 PloS one Result HIV I559P 109 114 gp120;gp41 77;125 82;129 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, some but not all of the inhibitory effects of the I559P gp41 change on gp120 transitions to the CD4-bound state can be compensated by the SOS modification. 2015 PloS one Result HIV I559P 56 61 gp120;gp41 77;62 82;66 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, the Env complexes with the I559P changes exhibit significant changes in the surface exposure of epitopes recognized by antibodies generated in a subset of HIV-1-infected subjects. 2015 PloS one Result HIV I559P 33 38 Env 10 13 HIV infections 161 175 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, the I559P change dramatically compromises Env-mediated membrane fusion, in the context of either a wt or SOS Env background. 2015 PloS one Result HIV I559P 10 15 Env;Env 48;115 51;118 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, the I559P change significantly alters the conformation of gp41 in a manner that is minimally compensated by the SOS modification. 2015 PloS one Result HIV I559P 10 15 gp41 64 68 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, the major conformational changes induced by the I559P change in the membrane-anchored Env are independent of the presence of the gp41 cytoplasmic tail. 2015 PloS one Result HIV I559P 54 59 gp41;Env 135;92 139;95 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. To test whether the dramatic effects of the I559P change on Env conformation (Fig 8 and Table 2) were dependent on the truncation of Env, we performed additional cell-based ELISA experiments using the full-length HIV-1BG505 gp160 envelope glycoproteins. 2015 PloS one Result HIV I559P 44 49 Env;gp160;Env;Env 230;224;60;133 238;229;63;136 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. We evaluated the effect of the I559P change on HIV-1BG505 Env function in the absence and presence of the SOS modification. 2015 PloS one Result HIV I559P 31 36 Env 58 61 25860884 SiRNA-induced mutation in HIV-1 polypurine tract region and its influence on viral fitness. Moreover, introducing an F185K solubility enhancing mutation into the integrase gene of HIV has been shown to severely impair, and in some cases completely prevent virus replication. 2015 PloS one Result HIV F185K 25 30 IN 70 79 25860884 SiRNA-induced mutation in HIV-1 polypurine tract region and its influence on viral fitness. Two of the non-replicating viruses were engineered to contain a T(-16)A mutation within the cPPT, and this mutation would be expected to cause a TTT-to-TTA codon change and corresponding F185L substitution within the amino acid sequence of integrase. 2015 PloS one Result HIV F185L 187 192 IN 240 249 25879488 Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011. K101E mutation can cause intermediate resistance to NVP and delairdine (DLV) and low-level resistance to EFV and etravirine (ETR). 2015 BMC public health Result HIV K101E 0 5 25879488 Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011. They are K101E and V179D mutation. 2015 BMC public health Result HIV K101E;V179D 9;19 14;24 25879488 Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011. V179D mutation is a borderline/suspicious mutation associated with transmitted HIVDR can reduce the susceptibility of NVP, EFV, and ETR against HIV. 2015 BMC public health Result HIV V179D 0 5 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. This indicated that SHIV with K65R mutation, although infectious, is not as efficient as wildtype virus in inducing SHIV-specific T cell responses (P=0.003, Fisher's exact test to compare the two proportions). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 30 34 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. We examined induction of SHIV-specific T cell responses in animals on topical PrEP with vaginal tenofovir gel and challenged with a drug-resistant virus containing the K65R point mutation (SHIVSF162P3-K65R). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R;K65R 168;201 172;205 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. Africans have a high risk of developing the K103N NNRTI mutation, which is connected to poor adherence, due to a common genetic polymorphism that causes slow plasma NNRTI clearance and functional NNRTI monotherapy, when treatment is interrupted. 2015 Virology journal Result HIV K103N 44 49 NNRTI;NNRTI;NNRTI 50;165;196 55;170;201 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. Among the 15 patients tested for resistance (Table 2), the most common NRTI mutation was M184V (4/15 patients, 27%). 2015 Virology journal Result HIV M184V 89 94 NRTI 71 75 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. The most common NNRTI resistance mutation was K103N (5/12, 42%), which caused high-level resistance against efavirenz and nevirapine. 2015 Virology journal Result HIV K103N 46 51 NNRTI 16 21 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. E157Q is an integrase polymorphic accessory mutation that is weakly selected in patients receiving raltegravir (RAL) and causes low level resistance to RAL and elvitegravir (EVG). 2015 Virology journal Result HIV E157Q 0 5 IN 12 21 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. L74I is an accessory mutation for integrase. 2015 Virology journal Result HIV L74I 0 4 IN 34 43 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. The K101E mutation found on the 0189A sequence causes intermediate resistance to NVP and low-level resistance to EFV, ETR, and RPV. 2015 Virology journal Result HIV K101E 4 9 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. The NNRTI mutation K103N detected on the 0143A sequence causes high-level resistance to nevirapine (NVP), and efavirenz (EFV). 2015 Virology journal Result HIV K103N 19 24 NNRTI 4 9 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. The NNRTI mutation, E138A, detected on the 0143A sequence is a polymorphism that may contribute to reduced etravirine (ETR) and rilpivirine (RPV) susceptibility in combination with other NNRTI-resistance mutations. 2015 Virology journal Result HIV E138A 20 25 NNRTI;NNRTI 4;187 9;192 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. The T74S minor PI mutation occurs in 5% of untreated persons with subtype C viruses and is associated with reduced NFV susceptibility. 2015 Virology journal Result HIV T74S 4 8 PI 15 17 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. D had virological failure at week 40 (with the PI mutation M46I in 1 of 38 single genomes) but achieved a viral load less than 400 copies per milliliter by week 96 of early ART that was maintained until the end of the CHER trial. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M46I 61 65 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. All SGS variants contained M184V and V82A by week 224. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V;V82A 27;37 32;41 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. At week 40 of ART, there was a viral load rebound to 96,400 copies per milliliter, and the majority species (67%) contained M184V and V82A. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V;V82A 124;134 129;138 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. Bulk sequence analyses detected baseline NVP-selected resistance in 5 of 10 children: K103N, V106M, and Y188C in 1 child each and Y181C in 2 children. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;V106M;Y181C;Y188C 86;93;130;104 91;98;135;109 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. By week 298, during restarted ART, the VL was measured at 7440 copies per milliliter with dual-class drug resistance in 95% of the viral population (n = 39 sequences), where these variants contained M184V genetically linked to 3 major and 2 minor PI-resistant mutations (Table 5). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 199 204 PI 247 249 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. Despite the high frequency of M46I, it was also not detected by bulk sequence analysis. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M46I 30 34 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. Emergence of V108I after ART initiation was not statistically supported (P = 0.189 for test of proportions of genomes carrying V108I between baseline and week 298). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV V108I;V108I 13;127 18;132 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. In "H," K101E was detected at week 40 of ART at a frequency of 7% but was not detected by bulk sequencing at either time point (Table 3). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV K101E 8 13 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. In "I," 92% (n = 37 sequences) of the viral population contained M184V only at week 12 of ART while the viral load fell from 750,000 copies per milliliter or greater at baseline to 7000 copies per milliliter at week 24 of ART. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 65 70 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. In "J," the first viral load rebound was seen between weeks 24 and 40 of early ART when the viral load rebounded from 3570 copies per milliliter at week 24 of early ART to greater than 750,000 copies per milliliter at week 40 of ART without the detection of multiple linked multiclass drug resistance; the quasispecies contained wild-type virus (47%), M184V (45%), and NNRTI DRMs at a combined frequency of 8% (n = 38 sequences). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 352 357 NNRTI 369 374 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. In "J," Y181C was detected at a frequency of 5% at week 40 of ART with SGS but was not detected by bulk sequence analysis at this time point. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 8 13 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. M184V was the first DRM to be detected in both "I" and "J" who had virological failure with DRMs known to confer resistance to components of ART (Tables 4 and 5). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 0 5 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. M46L could have been present at baseline given that only 1/32 genomes contained this mutation at week 96 (P = 0.457, Fisher's exact test of the proportion of sequences with M46L at baseline versus week 96 of ART). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M46L;M46L 173;0 177;4 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. More than 1 RT DRM linked on the same genome were detected in 2 children: in "J," Y181C was linked with V106M (2%, n = 49 sequences) and K219N (2%); in "E," Y181C linked with the accessory TAM, K219N, was detected (3%, n = 30 sequences) and linked dual-class resistance (Y181C with L74V) was also detected (7%) in the baseline viral population of this child. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV K219N;K219N;L74V;V106M;Y181C;Y181C;Y181C 137;194;282;104;82;157;271 142;199;286;109;87;162;277 RT 12 14 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. PI and NRTI DRMs were detected by SGS only and at baseline in 2 children, "D" and "E." These were T215I (5%, n = 21 sequences) in "D" and the major PI DRM I50V (3%, n = 30 sequences) in "E." T215I is not known to confer NRTI resistance rather it is a reversion mutation of the thymidine analog mutation (TAM) T215F/Y. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV I50V;T215F;T215I;T215I;T215Y 155;307;98;191;307 159;316;103;196;316 NRTI;NRTI;PI;PI 7;220;0;148 11;224;2;150 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. SGS revealed 29% of variants at week 96 of ART contained genetically linked M184V and V82A, but bulk sequencing did not detect V82A at this time point. 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V;V82A;V82A 76;86;127 81;90;131 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. The NNRTI mutation V108I was first detected at week 96 of ART at a frequency of 3% and again detected at a frequency of 5% at week 298 (Table 3). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV V108I 19 24 NNRTI 4 9 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. The NRTI mutation M184V (selected by 3 TC) and the PR mutation V82A (selected by LPV) were observed at weeks 40 and 96 of ART for "I" (Table 4). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V;V82A 18;63 23;67 NRTI;PR 4;51 8;53 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. The variant contained M184V, V108I in RT, and M46I in PR (Table 5). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V;M46I;V108I 22;46;29 27;50;34 PR;RT 54;38 56;40 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. The viral load later rebounded to 326,000 copies per milliliter at week 96 while receiving additional RTV, this time with dual-class drug resistance (M184V genetically linked to V82A or M46I) detected in the majority species (68%, n = 32 sequences). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V;M46I;V82A 150;186;178 156;190;182 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. Two other dual-class drug-resistant variants were detected by SGS at week 96 of ART involving M184V linked to mutations at position 46 of protease (Table 5). 2015 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 94 99 PR 138 146 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Among K103N, Y181C and G190A, some correlations could be found, but they were not always positively correlated, the correlated mutations network changed with the time of ART. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 23;6;13 28;11;18 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Besides the mutations conferring drug resistance effect, there were a number of accessory mutations or compensatory mutations that correlated with the three NNRTI mutations, more specifically, 5 mutations for G190A in 12 months 14 ones for K103N, and 9 for Y181C. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 209;240;257 214;245;262 NNRTI 157 162 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. For example, in standard genotype sequencing dataset when receiving ART for 12 months Y181C, G190A and H221Y were positively correlated with K103N, but when receiving ART for over 60 months, Y181C and H221Y were positively correlated with K103N, while G190A was not. 2014 AIDS research and therapy Result HIV G190A;G190A;H221Y;H221Y;K103N;K103N;Y181C;Y181C 93;252;103;201;141;239;86;191 98;257;108;206;146;244;91;196 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Frequency of K103N showed a decreasing trend while both the frequency of Y181C and G190A showed an increasing trend. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 83;13;73 88;18;78 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Here we showed the frequency of K101E in each time points. 2014 AIDS research and therapy Result HIV K101E 32 37 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In NNRTI mutations besides K103N, Y181C and G190A themselves, H221Y was the most common NNRTI mutations associated with the three NNRTI mutations. 2014 AIDS research and therapy Result HIV G190A;H221Y;K103N;Y181C 44;62;27;34 49;67;32;39 NNRTI;NNRTI;NNRTI 3;88;130 8;93;135 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In patient ANHDRC106, the frequency of K101E increased from 0% to 100% in 46.4 months, while the frequency of G190A increased from 10% to maximum 84.6% in 46.4 months. 2014 AIDS research and therapy Result HIV G190A;K101E 110;39 115;44 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In patient HENDRC593, the frequency of K101E increased from 64.7% to 100% in 49.9 months, while the frequency of G190A increased exactly from 64.7% to 100% in 49.9 months. 2014 AIDS research and therapy Result HIV G190A;K101E 113;39 118;44 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In patients ANHDRC106, after taking ART for 23.9 months, K103N and Y181C became dominant mutations (100%), while the frequency of G190A was 10%. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 130;57;67 135;62;72 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In patients HENDRC622, K103N showed a decreasing trend from 20.5 to 61.5 months, while G190A kept 100% in quasispecies. 2014 AIDS research and therapy Result HIV G190A;K103N 87;23 92;28 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In patients HENDRC622, the frequency of G190A kept in 100% in nearly all time points, while the frequency of K101E kept under 30%. 2014 AIDS research and therapy Result HIV G190A;K101E 40;109 45;114 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In the dataset of receiving ART for over60 months, there were 35 mutations that correlated with G190A, 20 mutations for K103N, and 26 mutations for Y181C. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 96;120;148 101;125;153 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In the follow-up time points, K103N showed a decreasing trend and G190A showed an increasing trend, while Y181C maintained dominant. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 66;30;106 71;35;111 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In the patient HENDRC593, the frequency of K103N showed a decreasing trend, especially from 44.8 months, the K103N vanished in SGA sequences. 2014 AIDS research and therapy Result HIV K103N;K103N 43;109 48;114 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. It is interesting that the frequency of K101E changed with G190A. 2014 AIDS research and therapy Result HIV G190A;K101E 59;40 64;45 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. It showed that M41L, D67N, T69D, K70R, and K219R were the most common NRTI mutations that associated with the three NNRTI mutations, K103N, Y181C and G190A. 2014 AIDS research and therapy Result HIV D67N;G190A;K103N;K219R;K70R;M41L;T69D;Y181C 21;150;133;43;33;15;27;140 25;155;138;48;37;19;31;145 NNRTI;NRTI 116;70 121;74 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. More specifically, K103N decreased, while Y181C and G190A showed increasing trend (Table 2). 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 52;19;42 57;24;47 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. On the contrary, G190A showed a dramatic increasing trend from the initiation of ART. 2014 AIDS research and therapy Result HIV G190A 17 22 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Specifically, the frequency of K103N had a negative correlation with treatment duration, and mutation G190A had positive correlation with treatment duration. 2014 AIDS research and therapy Result HIV G190A;K103N 102;31 107;36 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Standard genotyping: the frequency of K103N, Y181C and G190A in long-term cohort study. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 55;38;45 60;43;50 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The correlated mutations with K103N, Y181C and G190A (result of cKa/Ks ratio) 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 47;30;37 52;35;42 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The correlated mutations with K103N, Y181C and G190A (result of cKa/Ks ratio). 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 47;30;37 52;35;42 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The frequencies of three primary NNRTI drug resistance mutations, K103N, Y181C and G190A, fluctuated during long-term ART. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 83;66;73 88;71;78 NNRTI 33 38 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The frequency of K103N, Y181C and G190A in SGA. 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 34;17;24 39;22;29 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The frequency of mutation Y181C and treatment duration did not show significant correlation. 2014 AIDS research and therapy Result HIV Y181C 26 31 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The research of Jiong Wang stated that mutation K101E + G190S replicate better with NNRTI drug. 2014 AIDS research and therapy Result HIV G190S;K101E 56;48 61;53 NNRTI 84 89 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The Y181C increased slightly from 0.0% to 31.6% from receiving ART for 44.7 months to 61.5 months. 2014 AIDS research and therapy Result HIV Y181C 4 9 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Then we calculated and analyzed the frequency of K103N, Y181C and G190A in the four time points (Figure 1). 2014 AIDS research and therapy Result HIV G190A;K103N;Y181C 66;49;56 71;54;61 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. We also analyzed the frequency of K101E in 204 patients, but here we showed the correlated rate of K101E and G190A in four time points, they were 3/9, 4/16, 7/23, 10/27 (about 30%). 2014 AIDS research and therapy Result HIV G190A;K101E;K101E 109;34;99 114;39;104 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. At baseline, one or more primary PI RAMs were found in 10 patients (3%; nine treatment-naive, and one treatment-experienced), most commonly M46I/L (three treatment-naive and one treatment-experienced) and Q58E (four treatment-naive). 2014 AIDS research and therapy Result HIV M46I;M46L;Q58E 140;140;205 146;146;209 PI 33 35 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. N[t]RTI RAMs were found in 14% of patients (43/313; 36 and seven patients), most commonly V118I (6%; 18/313; 18 and zero patients), T69D/N (3%; 8/313; eight and zero patients) and M184V/I (3%; 8/313; two and six patients). 2014 AIDS research and therapy Result HIV M184I;M184V;T69D;T69N;V118I 180;180;132;132;90 187;187;138;138;95 NRTI 0 7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. Non-nucleoside reverse transcriptase inhibitor (NNRTI) RAMs were found in 28% of patients (87/313; 74 and 13 patients), most commonly K103N/S (13%; 41/313; 33 and eight patients). 2014 AIDS research and therapy Result HIV K103N;K103S 134;134 141;141 NNRTI;NNRTI 0;48 36;53 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. One patient (patient 14 in Table 4) showed the transient development of the N[t]RTI RAM L74I/L and the NNRTI RAM P225H/P at the Week 16 visit, which were not detected at the subsequent Week 48 visit analysis as shown in Table 4. 2014 AIDS research and therapy Result HIV L74I;L74L;P225H;P225P 88;88;113;113 94;94;120;120 NRTI;NNRTI 76;103 83;108 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. Only one of these 15 patients who was treatment experienced (prior antiretrovirals included efavirenz, emtricitabine, tenofovir disoproxil fumarate, zidovudine, lamivudine, stavudine) developed a resistance mutation to darunavir (at position I84 as a mixture with wild-type, I84I/V) (Table 4); this was not associated with phenotypic resistance to darunavir or other PIs. 2014 AIDS research and therapy Result HIV I84I;I84V 275;275 281;281 PI 367 370 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. Two patients (one treatment-experienced and one treatment-naive) developed the M184V N[t]RTI RAM in reverse transcriptase while receiving emtricitabine (Table 4) that was associated with phenotypic resistance to emtricitabine and lamivudine. 2014 AIDS research and therapy Result HIV M184V 79 84 RT;NRTI 100;85 121;92 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. A compensatory E138K mutation decreased the resistance of INBQ148K to RAL and EVG almost twofold, without a significant effect on the resistance of the INAQ148K mutant. 2015 Acta naturae Result HIV E138K 15 20 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. A compensatory effect of E138K on the catalytic activity of both INs with the primary Q148K substitution was also detected. 2015 Acta naturae Result HIV E138K;Q148K;E138K;Q148K 26;87;25;86 31;92;30;91 IN 65 68 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. A similar observation was made earlier for HIV-1 subtype B: the addition of the E138K mutation to the Q148K/G140S substitutions improved viral replication while not affecting viral sensitivity to strand transfer inhibitors . 2015 Acta naturae Result HIV E138K;G140S;Q148K 80;108;102 85;113;107 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. A single G118R mutation reduced the INB sensitivity more significantly (Table 2). 2015 Acta naturae Result HIV G118R 9 14 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. As a result, INA containing a G118R substitution is significantly less active in the strand transfer reaction than the corresponding INB mutant. 2015 Acta naturae Result HIV G118R 30 35 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. As for subtype A IN mutants, INAG118R and INAG118R/E138K, they demonstrated equally low activities, although the substitution E138K alone resulted in increased efficiency of heterologous strand transfer catalyzed by INs of both subtypes. 2015 Acta naturae Result HIV E138K;E138K;G118R 51;126;45 56;131;50 IN;IN 17;216 19;219 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. As we expected based on published data , the negative effect of the primary mutation Q148K was partially recompensed by the G140S substitution. 2015 Acta naturae Result HIV G140S;Q148K 125;86 130;91 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Despite the negative effect of the G140S substitution, its combination with the Q148K mutation increased the reaction efficiency and the double mutants INAG140S/Q148K and INBG140S/Q148K were more active than INAQ148K and INBQ148K. 2015 Acta naturae Result HIV G140S;G140S;G140S;Q148K;Q148K;Q148K 35;155;174;80;161;180 40;160;179;85;166;185 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. FC analysis of the protein family containing the primary substitution Q148K (INQ148K, INE138K/Q148K and ING140S/ Q148K) showed that the resistance of the mutant INs of both subtypes to EVG increased in a similar manner (Table 2). 2015 Acta naturae Result HIV Q148K;Q148K;Q148K 70;94;113 75;99;118 IN;IN;IN;IN 77;86;104;161 79;88;106;164 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Finally, we found that the G118R substitution strongly decreased the activities of both INA and INB. 2015 Acta naturae Result HIV G118R 28 33 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Fourteen mutant proteins (seven for each IN: Q148K, G140S, E138K, G118R, Q148K/E138K, Q148K/G140S, and G118R/E138K) were prepared by site-directed mutagenesis for the comparative analysis of the effect of drug resistance mutations on the catalytic activity of INs of FSU-A (INA) and HXB-2 (INB) strains. 2015 Acta naturae Result HIV E138K;E138K;E138K;G118R;G118R;G140S;G140S;Q148K;Q148K;Q148K;E138K;E138K;E138K;G118R;G118R;G140S;G140S;Q148K;Q148K;Q148K 60;80;110;67;104;53;93;46;74;87;59;79;109;66;103;52;92;45;73;86 65;85;115;72;109;58;98;51;79;92;64;84;114;71;108;57;97;50;78;91 IN;IN 41;260 43;263 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. However, both double mutants INA E138K/Q148K and INBE138K/Q148K were less active than the double mutants carrying the G140S/Q148 substitutions. 2015 Acta naturae Result HIV E138K;E138K;G140S;Q148K;Q148K 33;52;118;39;58 38;57;123;44;63 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. However, it should be noted that the compensatory effect of G140S on the Q148K mutation observed for INAQ148K and INBQ148K was not as significant as on the Q148H substitution in INB. 2015 Acta naturae Result HIV G140S;Q148H;Q148K 60;156;73 65;161;78 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. However, the efficiency of the homologous strand transfer catalyzed by INAG118R/E138K was only 23% of the reaction catalyzed by the wt INA. 2015 Acta naturae Result HIV E138K;G118R 80;74 85;79 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. In general, the primary mutation Q148K and its compensatory substitutions G140S and E138K equally affected the activities of INA and INB during 3'-processing and strand transfer reactions. 2015 Acta naturae Result HIV E138K;G140S;Q148K 84;74;33 89;79;38 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. INs of both subtypes carrying the Q148K substitution were the least active in the strand transfer reaction, identically to 3'-processing. 2015 Acta naturae Result HIV Q148K 35 40 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Interestingly, activity of INA with triple mutation E138K/G140S/Q148K was slightly higher than that of the enzymes with two substitutions: 1,500 min after initiation of the reaction, the 3'-processing efficiency for the triple mutant was about 30% of that for the wt INA, while for the most active double mutant INAG140S/Q148K it was not higher than 20% (Table 1). 2015 Acta naturae Result HIV E138K;G140S;Q148K;G140S;Q148K 52;58;64;315;321 57;63;69;320;326 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Interestingly, the compensatory E138K substitution reduced the emerging resistance (Table 2). 2015 Acta naturae Result HIV E138K 32 37 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It is important that another group of mutations, G118R and G118R/E138K, exhibited a different effect on the activity of INs of different subtypes in strand transfer reactions. 2015 Acta naturae Result HIV E138K;G118R;G118R;E138K;G118R 66;50;60;65;49 71;55;65;70;54 IN 120 123 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It is interesting to note that a single E138K substitution significantly increased the reaction efficiency for INs of both subtypes. 2015 Acta naturae Result HIV E138K 40 45 IN 111 114 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It is interesting to note that the secondary E138K substitution increased the sensitivity of the INAQ148K and INBQ148K mutants to XZ-259, while G140S reduced their sensitivity (Table 2). 2015 Acta naturae Result HIV E138K;G140S 45;144 50;149 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It should also be noted that in the case of INA, the G118R mutation resulted in a changed integration profile, and only two predominant products were detected for INAG118R instead of the large set of products found for wt INA. 2015 Acta naturae Result HIV G118R 53 58 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It should also be noted that the sensitivity of both Q148K mutants to XZ-259 was significantly higher than the sensitivity to EVG and especially to RAL; these results were in agreement with the results obtained earlier for INB. 2015 Acta naturae Result HIV Q148K 53 58 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It should be noted that Ser119 is likewise present in drug-resistant strains of HIV-1 subtype C, which most often contain the G118R mutation. 2015 Acta naturae Result HIV G118R 126 131 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. It was shown previously that G118R substitution in INB significantly (over 90%) reduces its activity in the heterologous strand transfer reaction . 2015 Acta naturae Result HIV G118R 30 35 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Moreover, the compensatory effect of G140S was somewhat stronger for INA, while the compensatory effect of E138K was stronger for for INB. 2015 Acta naturae Result HIV E138K;G140S 107;37 112;42 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Our study of the G118R effect on the ability of INA and INB to catalyze the heterologous strand transfer showed that, identically to the homologous strand transfer, the effect of this substitution on the enzymes of different HIV-1 subtypes is different. 2015 Acta naturae Result HIV G118R 17 22 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. RAL inhibited INA carrying the Q148K and G140S/Q148K substitutions twice more effectively than the corresponding INB variants. 2015 Acta naturae Result HIV G140S;Q148K;Q148K 41;31;47 46;36;52 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Similar effects were observed for HIV-1 subtype B containing these mutations: G118R substitution caused a significant decrease in the viral replication and integration, and the addition of the E138K mutation led to their partial recovery. 2015 Acta naturae Result HIV E138K;G118R 193;78 198;83 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Some compensatory effect was also produced by the E138K mutation. 2015 Acta naturae Result HIV E138K 50 55 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Surprisingly, the G140S substitution significantly decreased the reaction efficiency, too. 2015 Acta naturae Result HIV G140S 18 23 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The addition of the compensatory mutation E138K had virtually no effect on the activity of the INBG118R mutant, while the double mutant INAG118R/E138K was more active than INAG118R carrying a single substitution. 2015 Acta naturae Result HIV E138K;E138K;G118R 42;145;139 47;150;144 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The compensatory effect of G140S was stronger for INA: the difference in the 3'-processing efficiency and initial rate for mutants INAG140S/Q148K and INAQ148K was more pronounced than that for the corresponding pair of subtype B. 2015 Acta naturae Result HIV G140S;G140S;Q148K 27;134;140 32;139;145 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The difference in the activities of IN with the primary mutations Q148K and Q148N correlated with the differences in the integration capacity of viruses carrying these mutations. 2015 Acta naturae Result HIV Q148K;Q148N 66;76 71;81 IN 36 38 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The double mutation G118R/E138K resulted in partial recovery of the activity, but it failed to achieve even 50% of the wt IN activity. 2015 Acta naturae Result HIV E138K;G118R 26;20 31;25 IN 122 124 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The FC analysis of the protein family with G118R and G118R/E138K substitutions showed a slight decrease in the sensitivity of both subtypes INs to RAL and EVG (Table 2). 2015 Acta naturae Result HIV E138K;G118R;G118R;E138K;G118R;G118R 60;44;54;59;43;53 65;49;59;64;48;58 IN 140 143 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The G118R mutation decreased INB activity by approximately 50%, while the corresponding INAG118R mutant was virtually inactive. 2015 Acta naturae Result HIV G118R 4 9 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The most significant decrease was detected for proteins with the Q148K substitution; this finding is in good agreement with the previous results for INB. 2015 Acta naturae Result HIV Q148K 65 70 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The Pro119 and G118R mutations obviously affect the ability of INA to interact with the DNA target to a higher extent than a combination of Ser119 and G118R. 2015 Acta naturae Result HIV G118R;G118R 15;151 20;156 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The secondary substitution E138K had a compensatory effect only on INB: the activity of the INBG118R/E138K double mutant was somewhat higher than that of the INBG118R mutant. 2015 Acta naturae Result HIV E138K;E138K;G118R 27;101;95 32;106;100 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. This effect was observed for the enzymes of both subtypes, INA G140 and INB G140, though no data on a G140S negative effect on the activity of recombinant IN have been published, and only a slight decrease in the integration and replication capabilities was demonstrated for HIV-1 subtype B with this substitution . 2015 Acta naturae Result HIV G140S 102 107 IN 155 157 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. This finding is consistent with a decrease in the replication and integration activity of HIV-1 subtype B mutants in the series: Q148K < Q148K/E138K < Q148K/G140S. 2015 Acta naturae Result HIV E138K;G140S;Q148K;Q148K;Q148K 143;157;129;137;151 148;162;134;142;156 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. This may be explained by the stronger negative impact of the Q148K mutation on the IN activity. 2015 Acta naturae Result HIV Q148K 61 66 IN 83 85 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. This result contradicts the data reported in, which demonstrated that the efficiency of 3'-processing catalyzed by recombinant INB with the G118R substitution was slightly reduced, whereas the double mutants G118R/E138K and G118R/H51Y were somewhat more active than the wt enzyme. 2015 Acta naturae Result HIV E138K;G118R;G118R;G118R;H51Y 214;140;208;224;230 219;145;213;229;234 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Thus, our study confirms the heterogenic effect of the primary G118R mutation on the drug resistance of different HIV-1 subtypes. 2015 Acta naturae Result HIV G118R 63 68 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Thus, the compensatory effect of the combination of two mutations, E138K and G140S, was slightly higher than that of the individual secondary substitution, G140S or E138K. 2015 Acta naturae Result HIV E138K;E138K;G140S;G140S 67;165;77;156 72;170;82;161 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Thus, the HIV-1 subtype CRF02_A/G isolate carrying a G118R substitution in the IN gene was resistant (FC>100) to all IN inhibitors approved for therapeutic use: RAL, EVG, and DTG . 2015 Acta naturae Result HIV G118R 53 58 IN;IN 79;117 81;119 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Under our conditions, the introduction of the secondary E138K substitution also led to increased activities of both the INAG118R and INBG118R mutants; however, the activities of all enzymes with the G118R substitution were significantly lower than those of wt INA and INB. 2015 Acta naturae Result HIV E138K;G118R 56;199 61;204 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. (K103N and Y188C, K103N and G190AG, A98G and G190AG and Y188C and V90I). 2015 Journal of medical virology Result HIV A98G;G190A;G190A;G190G;G190G;K103N;K103N;V90I;Y188C;Y188C 36;28;45;28;45;2;18;66;11;56 40;34;51;34;51;6;23;70;16;61 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. Fifteen (34%) patients had mutations (viz K103N, Y181C, Y188C, Y188HY, and G190AG) associated with high level resistance to NNRTI, in particular NVP, whilst 1 (2%) patient had K101E associated with intermediate resistance to NNRTIs. 2015 Journal of medical virology Result HIV G190A;G190G;K101E;K103N;Y181C;Y188C;Y188H;Y188Y 75;75;176;42;49;56;63;63 81;81;181;47;54;61;69;69 NNRTI;NNRTI 124;225 129;231 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. No Thymidine analog mutations (TAMs) or M184V were detected. 2015 Journal of medical virology Result HIV M184V 40 45 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. T69S, a mutation which confers resistance to all NRTI's was found in one patient. 2015 Journal of medical virology Result HIV T69S 0 4 NRTI 49 53 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. The mutation most frequently detected was K103N, seen in 66% (10/15) of patients in whom a mutation conferring high-level NNRTI resistance was detected. 2015 Journal of medical virology Result HIV K103N 42 47 NNRTI 122 127 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. V90I and E138A were detected in each of two patients. 2015 Journal of medical virology Result HIV E138A;V90I 9;0 14;4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. Among the detected DRAMs (Table 2), M41L and M184V that confer the clinical resistance to zidovudine (AZT), lamivudine (3TC), stavudine (d4T) and abacavir (ABC) were the most common to nucleoside reverse transcriptase inhibitors (NRTIs; 5%). 2015 PloS one Result HIV M184V;M41L 45;36 50;40 NRTI;NRTI 185;230 217;235 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. Instead, T74S (2.5%) that is a common accessory mutation and V77I (2.5%) that confers moderate resistance to indinavir (IDV), nelfinavir (NFV) and saquinavir (SQV) were identified in our samples. 2015 PloS one Result HIV T74S;V77I 9;61 13;65 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. K103N associated with resistance to efavirenz (EFV) and nevirapine (NVP) was the only mutation to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 5%). 2015 PloS one Result HIV K103N 0 5 NNRTI;NNRTI 98;147 134;153 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. V11I, L33V and D60E that were already reported as minor PI DRAMs in CRF35_AD were not detected in Sanandaj samples. 2015 PloS one Result HIV D60E;L33V;V11I 15;6;0 19;10;4 PI 56 58 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. We found no SDRMs to protease inhibitors (PIs); however, based on the mutations listed in the International Antiviral Society-USA (IAS-USA) panel, 13minor mutations were detected in the PR region, of which M36I, H69K, and L89M/V/I were found in all 40 (100%) andK20R/T was detected in 37 (92.5%) samples. 2015 PloS one Result HIV H69K;L89I;L89M;L89V;M36I 212;222;222;222;206 216;230;230;230;210 PR;PI;PR 21;42;186 29;45;188 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. All 7 viruses harboring the mutations K103N and Y188L/F grouped apart in a subcluster supported by a bootstrap value of 100% (Fig 2). 2015 PloS one Result HIV K103N;Y188F;Y188L 38;48;48 43;55;55 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. All the 9 viruses harboring the K103N mutation grouped apart in a subcluster supported by a bootstrap value of 96%. 2015 PloS one Result HIV K103N 32 37 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Among the 44 sequences with TDR to PIs, the most common mutations were L90M (47.7%), M46L/I (33.3%), I54V/T (21.4%), and V82A (19%). 2015 PloS one Result HIV I54T;I54V;L90M;M46I;M46L;V82A 101;101;71;85;85;121 107;107;75;91;91;125 PI 35 38 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Cluster B-2 comprised 15 individuals, 10 of them newly diagnosed between 2007 and 2012, in 6 of whom the K103N mutation, associated with high level resistance to first generation NNRTIs (nevirapine and efavirenz), was detected. 2015 PloS one Result HIV K103N 105 110 NNRTI 179 185 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Cluster B-3 comprised 4 newly diagnosed individuals with dates of diagnosis between 2008 and 2012, three of whom harbored the major mutations K103N and Y188L/F, associated with high level resistance to NNRTIs (nevirapine, efavirenz and rilpivirine). 2015 PloS one Result HIV K103N;Y188F;Y188L 142;152;152 147;159;159 NNRTI 202 208 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Considering the 79 sequences with TDR to NRTIs, thymidine analogue mutations (TAMs) were the most frequently detected, of which the most common were T215 revertants, present in 48 (60.7%) individuals, M41L in 20 (25.3%), K219Q/R/N/E in 19 (24%), L210W in 14 (17.7%), and D67N in 13.9%. 2015 PloS one Result HIV D67N;K219E;K219N;K219Q;K219R;L210W;M41L 271;221;221;221;221;246;201 275;232;232;232;232;251;205 NRTI 41 46 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Finally, all 25 individuals clustering in B-4 harbored the T215D revertant drug resistance mutation (Fig 2). 2015 PloS one Result HIV T215D 59 64 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. It is noteworthy that several major mutations associated to high level resistance to NRTIs (K65R, L74V, Y115F, M184V and T215Y), to NNRTIs (l100I, K101E, K103N/S, V106M, Y181C, Y188L and G190A) and to PIs (D30N, M46I/L, I54V/T, L76V, V82A, I84V, N88D and L90M) were detected. 2015 PloS one Result HIV D30N;G190A;I54T;I54V;I84V;K101E;K103N;K103S;K65R;L74V;L76V;L90M;M184V;M46I;M46L;N88D;T215Y;V106M;V82A;Y115F;Y181C;Y188L 206;187;220;220;240;147;154;154;92;98;228;255;111;212;212;246;121;163;234;104;170;177 210;192;226;226;244;152;161;161;96;102;232;259;116;218;218;250;126;168;238;109;175;182 NNRTI;NRTI;PI 132;85;201 138;90;204 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L90M was detected in all viruses of both clusters, except in one of three viruses from Portugal whose sequences were retrieved from GenBank clustering in C-1. 2015 PloS one Result HIV L90M 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. The L90M major mutation in protease, associated with high level resistance to atazanavir/ritonavir, indinavir/ritonavir, fosamprenavir/ritonavir, nelfinavir and saquinavir/ritonavir, was transmitted in clusters B-1 and C-1, which comprised 9 and 4 newly diagnosed individuals, respectively. 2015 PloS one Result HIV L90M 4 8 PR 27 35 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. The M184V/I major resistance mutation was detected in 8 (10.1%) of the 79 sequences. 2015 PloS one Result HIV M184I;M184V 4;4 11;11 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. With regard to the 58 sequences with TDR to NNRTIs, the most frequent mutations were K103N/S (63.8%), K101E (13.8%), and Y181C (12.1%). 2015 PloS one Result HIV K101E;K103N;K103S;Y181C 102;85;85;121 107;92;92;126 NNRTI 44 50 26020400 Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China. Two TDR mutations, M46I (2) and I50V (1) were found in the protease region, and the other eight TDR mutations, K65E(1), D67N(1), T69N(1), K103N(1), Y181C(2), G190E(1), L210W(1), and P225H(1) were from the reverse transcriptase fragment. 2015 Medicine Result HIV D67N;G190E;I50V;K103N;K65E;L210W;M46I;P225H;T69N;Y181C 120;158;32;138;111;168;19;182;129;148 124;163;36;143;115;173;23;187;133;153 RT;PR 205;59 226;67 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. M184V was selected in 16 (70%) subjects: 12 treated with 3TC and 4 with FTC (p = 0.04). 2015 PloS one Result HIV M184V 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Seven patients had K65R (6 associated to M184V, none with thymidine-analogue mutations [TAMs]), 5 of them treated with 3TC and 2 with FTC. 2015 PloS one Result HIV K65R;M184V 19;41 23;46 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Six patients selected A62V, with K65R selected in 4 of them, and none with Q151M or T69 insertions. 2015 PloS one Result HIV A62V;K65R;Q151M 22;33;75 26;37;80 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Sixteen out of 23 (70%) had NNRTI mutations (Y181C/I/D: 10; K103N: 6; V106A/I: 3; Y188C/L: 2; K101Q/E: 2; M230L: 1; P225H: 1; A98G: 1; V108I: 1; F227L: 1; K238T: 1), and 10 had >1 NNRTI mutation. 2015 PloS one Result HIV A98G;F227L;K101E;K101Q;K103N;K238T;M230L;P225H;V106A;V106I;V108I;Y181C;Y181D;Y181I;Y188C;Y188L 126;145;94;94;60;155;106;116;70;70;135;45;45;45;82;82 130;150;101;101;65;160;111;121;77;77;140;55;55;55;89;89 NNRTI;NNRTI 28;180 33;185 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Three subjects harboured major protease mutations (V32I, M46I, I47V, L90M), selected in prior failures. 2015 PloS one Result HIV I47V;L90M;M46I;V32I 63;69;57;51 67;73;61;55 PR 31 39 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. A control experiment was performed with antiretroviral 3TC in order to guarantee HIV M184V resistance profile (Figure 3A). 2015 Molecules (Basel, Switzerland) Result HIV M184V 85 90 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Although the resistance to TNF and FTC has been rare and was primarily observed during PrEP initiation in those with acute HIV infection, an advantage of taking emetine in PrEP studies lies in the fact that it was effective against HIV M184V mutant virus and this characteristic could overcome the issue of resistance once M184V is a signature mutation for 3TC and FTC. 2015 Molecules (Basel, Switzerland) Result HIV M184V;M184V 236;323 241;328 HIV infections 117 136 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. For this reason, we checked the virus infectivity of HIV and viruses harboring the RT resistance mutation M184V 48 h post-infection. 2015 Molecules (Basel, Switzerland) Result HIV M184V 106 111 RT 83 85 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. In contrast with 3TC, emetine was able to block HIV wild-type and M184V virus in GHOST cells and PBMCs, and these results are promising, pointing at a positive use of emetine in the treatment of multidrug-resistant patients. 2015 Molecules (Basel, Switzerland) Result HIV M184V 66 71 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Next, we evaluated the inhibitory potential of emetine against HIVwild type and RT-resistant virus M184V in PBMCs. 2015 Molecules (Basel, Switzerland) Result HIV M184V 99 104 RT 80 82 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Our results showed that emetine at 0.03 microM reduced up to 80% of the infection of both,HIV wild-type and M184V viruses (Figure 4B) with lower cytotoxic effects (Figure 4C). 2015 Molecules (Basel, Switzerland) Result HIV M184V 108 113 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. The 3TC EC50 calculated in PBMCs infected with HIV wild-type virus was 0.0072 microM compared with 4.5 microM for HIV-M184V (Figure 4A). 2015 Molecules (Basel, Switzerland) Result HIV M184V 118 123 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. The same profile of HIV inhibition was observed with HIV M184V virus, meaning that emetine is able to block the replication of HIV-resistant virus. 2015 Molecules (Basel, Switzerland) Result HIV M184V 57 62 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. We also evaluated the capability of emetine to inhibit the replication of an HIV-resistant NRTI carrying the M184V mutation. 2015 Molecules (Basel, Switzerland) Result HIV M184V 109 114 NRTI 91 95 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. In gp41, 3 mutations were observed: K77Q adjacent to HR1 domain, N113D, which belongs to glycosylation sequon "NXT" and H132Y inside HR2 domain. 2015 PloS one Result HIV H132Y;K77Q;N113D 120;36;65 125;40;70 gp41 3 7 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. The HIV-1 NL4.3LAresistant virus acquired four mutations throughout gp120: S160N in the V2 loop, V170N in the C2 region, Q280H in the V3 loop and R389T in the C5 region. 2015 PloS one Result HIV Q280H;R389T;S160N;V170N 121;146;75;97 126;151;80;102 gp120 68 73 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. Two additional mixed mutations were found at R118K/R and A310A/V. 2015 PloS one Result HIV A310A;A310V;R118K;R118R 57;57;45;45 64;64;52;52 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. M184V (71%) and M41L (30%) were the two most common NRTI RAMs, and L90M (24%) and V82A (17%) the two most common PI-major RAMs. 2016 Journal of medical virology Result HIV L90M;M41L;V82A;M184V 67;16;82;0 71;20;86;5 NRTI;PI 52;113 56;115 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Protease (PR) RAMs detected from this outlier sample were M46I, I47V and I84V, and reverse transcriptase (RT) RAMs were A62V, D67N, K70R, V75I, F116Y, Q151M and K219Q. 2016 Journal of medical virology Result HIV A62V;D67N;F116Y;I47V;I84V;K219Q;K70R;M46I;Q151M;V75I 120;126;144;64;73;161;132;58;151;138 124;130;149;68;77;166;136;62;156;142 RT;PR;PR;RT 83;0;10;106 104;8;12;108 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. RT RAMs were A62V, D67N, V75I, F77L, K101H, Y115F, F116Y, Q151M, Y181C, G190A and K219E. 2016 Journal of medical virology Result HIV A62V;D67N;F116Y;F77L;G190A;K101H;K219E;Q151M;V75I;Y115F;Y181C 13;19;51;31;72;37;82;58;25;44;65 17;23;56;35;77;42;87;63;29;49;70 RT 0 2 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. The most common NNRTI RAM was K103N (65%) followed by Y181C (25%). 2016 Journal of medical virology Result HIV K103N;Y181C 30;54 35;59 NNRTI 16 21 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. The PR RAMs for this sample were V32I, I47V, I54L, V82A and L90M. 2016 Journal of medical virology Result HIV I47V;I54L;L90M;V32I;V82A 39;45;60;33;51 43;49;64;37;55 PR 4 6 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. The two most common NNRTI RAMs were V179D (16%) and V106I (15%); the most common NRTI RAMs were D67N (29%) and M184V (26%); and the most common PI-major RAMs were M46I (11%) and I84V (9%). 2016 Journal of medical virology Result HIV D67N;I84V;M184V;M46I;V106I;V179D 96;178;111;163;52;36 100;182;116;167;57;41 NNRTI;NRTI;PI 20;81;144 25;85;146 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. This sample was the only CRF01_AE sample with the Q151M mutation which is known to be associated with multiple NRTI drug resistance. 2016 Journal of medical virology Result HIV Q151M 50 55 NRTI 111 115 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. This was the only sample harbouring Q151M mutation out of all subtype B samples. 2016 Journal of medical virology Result HIV Q151M 36 41 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. Although NNRTIs were not used in this study, a minor NNRTI mutation K101K/E, as well as the 2 minor PI mutations L10F and L33F emerged at VF and RS to FPV was observed. 2015 The open AIDS journal Result HIV K101E;K101K;L10F;L33F 68;68;113;122 75;75;117;126 NNRTI;NNRTI;PI 9;53;100 15;58;102 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. ART-experienced Patient-4 selected a treatment-emergent RT mutation M184V at VF and the virus developed concomitant RS to emtricitabine/lamivudine. 2015 The open AIDS journal Result HIV M184V 68 73 RT 56 58 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. At VF, all three had HIV-1 with the treatment-emergent reverse transcriptase (RT) mutation M184V (individual response profiles are shown in Supplementary. 2015 The open AIDS journal Result HIV M184V 91 96 RT;RT 55;78 76;80 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. At VF, the following major treatment-emergent PI mutations or mutation mixtures were detected: M46M/I, I50I/V, I54I/M/V, and I84I/V, and the virus developed FPV RS. 2015 The open AIDS journal Result HIV I50I;I50V;I54I;I54M;I54V;I84I;I84V;M46I;M46M 103;103;111;111;111;125;125;95;95 109;109;119;119;119;131;131;101;101 PI 46 48 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. Of the PI mutations associated with darunavir drug resistance, only the minor mutation L33F or an L33L/F mutation mixture was treatment-emergent in virus from 2 patients at VF. 2015 The open AIDS journal Result HIV L33F;L33F;L33L 87;98;98 91;104;104 PI 7 9 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. The major PI treatment-emergent mutations selected at VF in virus from Patient-1 included M46M/L, I50I/V, I54I/L, and Q58Q/E, while virus from Patient-2 selected the V82V/A mutation. 2015 The open AIDS journal Result HIV I50I;I50V;I54I;I54L;M46L;M46M;Q58E;Q58Q;V82A;V82V 98;98;106;106;90;90;118;118;166;166 104;104;112;112;96;96;124;124;172;172 PI 10 12 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. The patient met VF criteria at week 24, at which time the major viral PI treatment-emergent mutations I50I/V, I54I/M, and V82F/I were detected. 2015 The open AIDS journal Result HIV I50I;I50V;I54I;I54M;V82F;V82I 102;102;110;110;122;122 108;108;116;116;128;128 PI 70 72 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. There were no treatment-emergent NRTI or PI mutations although a treatment-emergent NNRTI polymorphism V179V/D/E was detected. 2015 The open AIDS journal Result HIV V179D;V179E;V179V 103;103;103 112;112;112 NNRTI;NRTI;PI 84;33;41 89;37;43 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. Virus from ART-naive Patient-2 selected the NRTI M184V at VF, with concomitant RS to the NRTIs emtricitabine and lamivudine. 2015 The open AIDS journal Result HIV M184V 49 54 NRTI;NRTI 44;89 48;94 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. M184V (n = 27, 50.0%, 95% CI 36.7-63.3), T69N and D67N (n = 4, 7.4%) were the most common NRTI RAM among this therapeutic class. 2015 PloS one Result HIV D67N;T69N;M184V 50;41;0 54;45;5 NRTI 90 94 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. Of these, the most frequent mutations were K103N (n = 16, 24.2%, 95% CI 13.4-34.6) and Y181C (n = 15, 22.7%, 95% CI 12.6-32.8), and G190A (n = 10, 15.2%, 95% CI 6.5-23.8). 2015 PloS one Result HIV G190A;K103N;Y181C 132;43;87 137;48;92 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. PI resistance mutations were M46I (n = 5, 62.5%) and Q58E (n = 1, 12.5%), L90M (n = 2, 25.0%) (Fig 1). 2015 PloS one Result HIV L90M;M46I;Q58E 74;29;53 78;33;57 PI 0 2 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. The mutations K101H, V106M, Y181V and Y188L were found in only one sample each (Fig 2). 2015 PloS one Result HIV K101H;V106M;Y181V;Y188L 14;21;28;38 19;26;33;43 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. The NNRTI RAM most frequently represented in this ARV class were K103N (n = 16, 21.6%, 95% CI 12.2-31.0) and Y181C (n = 15, 20.3%, 95% CI 11.1-29.4) and G190A (n = 10, 13.5%, 95% CI 5.7-21.3). 2015 PloS one Result HIV G190A;K103N;Y181C 153;65;109 158;70;114 NNRTI 4 9 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. There were also multiple occurrences of V108I (n = 6), A98G (n = 6), K101E (n = 4), V106A (n = 4), K101P (n = 1). 2015 PloS one Result HIV A98G;K101E;K101P;V106A;V108I 55;69;99;84;40 59;74;104;89;45 26241860 The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon. When studying the distribution of the Y181C resistance mutation among the 100 samples collected from NNRTI-naive patients (77 H strains, 23 T strains), we observed that this profile was naturally present in 65 strains (65%), 62 of which were H strains and only 3 T strains. 2015 PLoS pathogens Result HIV Y181C 38 43 NNRTI 101 106 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. However, the A100D mutant was not immunoprecipitated by the HIV-2 Env. 2015 Retrovirology Result HIV A100D 13 18 Env 66 69 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. The lack of activity of mutant Rev A had implicated D830G as essential, but this further analysis revealed that both of the substitutions D830G and K796R were required. 2015 Retrovirology Result HIV D830G;D830G;K796R 52;138;148 57;143;153 Rev 31 34 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. The ROD14 Env differs from ROD10 Env at 5 specific amino acids, and contains a 30 amino acid deletion in its cytoplasmic tail, with substitutions K422R and A598T in the ectodomain of the protein being primarily responsible for its loss of tetherin antagonism. 2015 Retrovirology Result HIV A598T;K422R 156;146 161;151 Env;Env 10;33 13;36 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. These differences may be sufficient to account for its lack of anti-tetherin activity or, alternatively, this may result from some other characteristic of the Y707A mutant, such as being present in a different cellular localization than the WT Env, or because the loss of its endocytosis signal makes it unable to remove tetherin from the cell surface, as we and others have previously reported. 2015 Retrovirology Result HIV Y707A 159 164 Env 244 247 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. We have previously shown that an alanine to aspartic acid substitution at position 100 of tetherin (A100D) makes the protein resistant to the HIV-2 Env and a similarly located mutation in Tantalus monkey tetherin renders that protein resistant to SIVTan Env. 2015 Retrovirology Result HIV A100D;A100D 100;33 105;86 Env;Env 148;254 151;257 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. We next asked whether the HIV-2-resistant phenotype of tetherin A100D was a result of disrupting the interaction between the two proteins. 2015 Retrovirology Result HIV A100D 64 69 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. Analysis of SHIV reverse transcriptase sequences at time of infection confirmed the presence of K65R in all infected animals (data not shown). 2015 Retrovirology Result HIV K65R 96 100 RT 17 38 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. All 3 participants who had genotype testing showed RAMs; two had isolated RAMs (one E138K and the other Y181C), and the third had multiple RAMs (V75I, E138K, Y181C, M184I, K219E, and M230L). 2016 Antiviral therapy Result HIV E138K;E138K;K219E;M184I;M230L;V75I;Y181C;Y181C 84;151;172;165;183;145;104;158 89;156;177;170;188;149;109;163 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. Among the 37 screen failures, the most common reason for failure was presence of an exclusionary RAM at screening (n = 19; most common were K103N [5] and V179E/I/V [4]). 2016 Antiviral therapy Result HIV K103N;V179E;V179I;V179V 140;154;154;154 145;163;163;163 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. All HIV-1 strains in the C cluster carried the rare and atypical RT mutation K103Q (prevalence in non-B subtypes: 1.6% and 1.1% for drug-naive and drug-experienced patients, respectively, personal data), indicating the sharing of a virus characterized by a mutation at a position critical for Nevirapine and Efavirenz efficacy. 2015 PloS one Result HIV K103Q 77 82 RT 65 67 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. All viruses were R5-tropic, and were characterized by the V3 mutations H13R and E25D, known to be significantly associated with CXCR4 and CCR5 usage, respectively. 2015 PloS one Result HIV E25D;H13R 80;71 84;75 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. Analysing the HIV-1 CRF17_BF cluster, all strains carried the NNRTI resistance mutations K101E and E138K in the RT, thus showing the transmission of a resistant viral strain. 2015 PloS one Result HIV E138K;K101E 99;89 104;94 NNRTI;RT 62;112 67;114 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. By contrast, five patients carried HIV-1 strains characterized by a very high FPR (96.2%), explained by the presence of a double amino-acid change at 22 and 25 positions of the V3 region (T22A and E25D), known to be significantly associated with a CCR5 coreceptor usage, and the absence of the positive charge at position 32. 2015 PloS one Result HIV E25D;T22A 197;188 201;193 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. In particular, three patients carried strains characterized by an FPR of 25.3%, and by the X4 markers E25Q and Q32K. 2015 PloS one Result HIV E25Q;Q32K 102;111 106;115 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. This high FPR value can be explained by the presence of a single amino-acid change at position 10 of V3 region (K10E). 2015 PloS one Result HIV K10E 112 116 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Although major PI resistance mutations was not detected in the non-drug users, three major PI resistance mutations including L90M, M46I and D30N were detected in 4 (5.1 %) IDUs. 2015 AIDS research and therapy Result HIV D30N;L90M;M46I 140;125;131 144;129;135 PI;PI 15;91 17;93 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Fourteen (29.8 %) ART-experienced IDUs harboured only minor mutations comprising of 1(2.1 %) K20I, 7 (8.5 %) K20R, 3 (6.4 %) L10I, 1 (2.1 %) V32L and 2 (12.5 %) L10V+K20R. 2015 AIDS research and therapy Result HIV K20I;K20R;K20R;L10I;L10V;V32L 93;109;166;125;161;141 97;113;170;129;165;145 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. In addition, 13 (40.6 %) ART-naive IDUs had only minor mutations including 1 (3.1 %) G48E, 1 (3.1 %) G48R, 5 (15.6 %) K20R, 2 (6.3 %) L10I, 1 (3.1 %) L10V, 1 (3.1 %) L101+K20R and 2 (6.3 %) L10V + K20R. 2015 AIDS research and therapy Result HIV K20R;G48E;G48R;K20R;K20R;L10I;L10V;L10V 171;85;101;118;197;134;150;190 175;89;105;122;201;138;154;194 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. In addition, 14 (66.7 %) ART-naive non-drug users harboured minor mutations comprising of 1 (7.1 %) K20I, 8 (38.1 %) K20R, 2 (9.5 %) L10I, 1 (7.1 %) L101 + K20R, and 2 (9.5 %) L10V + V11I. 2015 AIDS research and therapy Result HIV K20I;K20R;K20R;L10I;L10V;V11I 100;117;156;133;176;183 104;121;160;137;180;187 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. In addition, D30N+M46I co-existed with G48E and K20I minor mutations, respectively, in 2 (4.2 %) ART-experienced IDUs. 2015 AIDS research and therapy Result HIV D30N;G48E;K20I;M46I 13;39;48;18 17;43;52;22 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. In non-drug users, 15 (46.9 %) ART-experienced individuals had minor mutations consisting of 5 (15.6 %) K20R, 2 (6.3 %) L10V, 2 (6.3 %) L33F, 1 (3.1 %) I13V + L63P, 1 (3.1 %) L10V + K20R, 3 (9.4 %) L10V + T74S and 1 (3.1 %) L33F + A71T. 2015 AIDS research and therapy Result HIV A71T;I13V;K20R;K20R;L10V;L10V;L10V;L33F;L33F;L63P;T74S 231;152;104;182;120;175;198;136;224;159;205 235;156;108;186;124;179;202;140;228;163;209 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Interestingly, mutation L90M co-existed with K20R minor mutation in 1 (2.1 %) ART-experienced IDU, while D30N co-existed with T74S+K20R minor mutations in 1 (3.1 %) ART-naive IDU. 2015 AIDS research and therapy Result HIV D30N;K20R;K20R;L90M;T74S 105;45;131;24;126 109;49;135;28;130 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. An additional four (1.6%) raltegravir recipients, all with subtype B, showed non-classic substitutions at major integrase resistance codons, comprising: (i) E92A, detected with the INI RAMs N155H and T97A (viral load 3170 copies/mL); (ii) S147I (viral load 477 copies/mL); (iii) N155D (viral load 140 copies/mL); and (iv) N155Q (viral load 111 copies/mL). 2015 The Journal of antimicrobial chemotherapy Result HIV E92A;N155D;N155H;N155Q;S147I;T97A 155;277;190;320;237;200 161;284;195;327;244;204 IN;IN 112;181 121;184 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Conversely, E92Q was significantly less frequent in subtype B (4/209, 1.9%) than in non-B clades (5/46, 10.9%) (P = 0.02), occurring in subtypes C (n = 2), G (n = 1), A (n = 1) and CRF09 (n = 1). 2015 The Journal of antimicrobial chemotherapy Result HIV E92Q 12 16 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Conversely, mutations that were mutually exclusive comprised E92Q and T97A with Q148H/R/K, and G140S/A with Y143R/C/H and N155H. 2015 The Journal of antimicrobial chemotherapy Result HIV E92Q;G140A;G140S;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143H;Y143R 61;95;95;122;80;80;80;70;108;108;108 65;102;102;127;89;89;89;74;117;117;117 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. G140A occurred in 3 subtype B sequences and 1 subtype G sequence, and Q148R occurred in 13 subtype B sequences, 1 subtype C sequence and 1 subtype G sequence. 2015 The Journal of antimicrobial chemotherapy Result HIV Q148R;G140A 70;0 75;5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. K159R + I161L occurred with Q148H + G140S, and E170A occurred with N155H and Q148H + G140S (Table S1, available as Supplementary data at JAC Online). 2015 The Journal of antimicrobial chemotherapy Result HIV E170A;G140S;G140S;I161L;N155H;Q148H;Q148H;K159R 47;36;85;8;67;28;77;0 52;41;90;13;72;33;82;5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Of these, L74M, T97A, E138K, V151I and G163R were significantly associated (P < 0.01) with raltegravir exposure. 2015 The Journal of antimicrobial chemotherapy Result HIV E138K;G163R;L74M;T97A;V151I 22;39;10;16;29 27;44;14;20;34 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Preferential associations comprised N155H with E92Q, Y143H/R/C with T97A and Q148H/R/K with G140S/A. 2015 The Journal of antimicrobial chemotherapy Result HIV E92Q;G140A;G140S;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143H;Y143R 47;92;92;36;77;77;77;68;53;53;53 51;99;99;41;86;86;86;72;62;62;62 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Reflecting the lower prevalence of the Q148H/R/K + G140A/S pathway, the prevalence of predicted dolutegravir cross-resistance among subjects with non-B clades was significantly lower than in subjects with subtype B, both overall (2/46, 4.3% versus 42/209, 20.1%; P = 0.009) and when restricting the comparison to subjects with intermediate- to high-level dolutegravir cross-resistance (1/46, 2.2% versus 39/209, 18.7%; P = 0.003). 2015 The Journal of antimicrobial chemotherapy Result HIV G140A;G140S;Q148H;Q148K;Q148R 51;51;39;39;39 58;58;48;48;48 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. The most commonly observed major INI RAMs were N155H (57, 22.4%), G140S (33, 12.9%), Q148H (28, 11.0%), Q148R (15, 5.9%), E92Q (9, 3.5%) and Y143R (9, 3.5%) (Table 1). 2015 The Journal of antimicrobial chemotherapy Result HIV E92Q;G140S;N155H;Q148H;Q148R;Y143R 122;66;47;85;104;141 126;71;52;90;109;146 IN 33 36 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. The most prevalent mutation profiles were N155H in isolation (45, 17.6%), Q148H/R/K + G140S/A (35, 13.7%) and Y143R/C/H in isolation (12, 4.7%). 2015 The Journal of antimicrobial chemotherapy Result HIV G140A;G140S;N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 86;86;42;74;74;74;110;110;110 93;93;47;83;83;83;119;119;119 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. The most prevalent mutations at these positions:G140S and Q148H:were exclusively found in subtype B sequences. 2015 The Journal of antimicrobial chemotherapy Result HIV G140S;Q148H 48;58 53;63 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. These mutations occurred in subtype B (K159Q/R, I161L/M/N/T/V and E170A/G) and CRF02_AG (I161L/T). 2015 The Journal of antimicrobial chemotherapy Result HIV E170A;E170G;I161L;I161L;I161M;I161N;I161T;I161T;I161V;K159Q;K159R 66;66;48;89;48;48;48;89;48;39;39 73;73;61;96;61;61;61;96;61;46;46 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. For NNRTIs, Y181C/I/V was below the CI and G190A/E/S was above the CI in both cohorts. 2015 AIDS (London, England) Result HIV G190A;G190E;G190S;Y181C;Y181I;Y181V 43;43;43;12;12;12 52;52;52;21;21;21 NNRTI 4 10 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. For NRTIs, K219N and T215rev were consistently above, whereas K70E, M184I/V, L210W and T215Y/F were below the CI. 2015 AIDS (London, England) Result HIV K219N;K70E;L210W;M184I;M184V;T215F;T215Y 11;62;77;68;68;87;87 16;66;82;75;75;94;94 NRTI 4 9 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. Highest transmission ratios were observed for N83D (0.165), N88D/S (0.134) and D30N (0.130) for protease inhibitors; T215Rev (0.727) (for T215Y/F was 0.029) and V75A/M/S/T (0.120) for NRTIs; and K101E/P (0.092) and G190A/E/S (0.091) for NNRTIs (Table 1). 2015 AIDS (London, England) Result HIV D30N;G190A;G190E;G190S;K101E;K101P;N83D;N88D;N88S;T215F;T215Y;V75A;V75M;V75S;V75T 79;215;215;215;195;195;46;60;60;138;138;161;161;161;161 83;224;224;224;202;202;50;66;66;145;145;171;171;171;171 PR;NNRTI;NRTI 96;237;184 104;243;189 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. In each class-specific analysis, some SDRMs were classified as outliers: for protease inhibitors, D30N, N88D/S, and L90 M were above; for NRTIs, M184I/V was below; and for NNRTIs G190A/E/S was above the regression line (Table S1, ). 2015 AIDS (London, England) Result HIV D30N;G190A;G190E;G190S;L90M;M184I;M184V;N88D;N88S 98;179;179;179;116;145;145;104;104 102;188;188;188;121;152;152;110;110 PR;NNRTI;NRTI 77;172;138 85;178;143 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. In treatment-failing patients, SDRMs with highest prevalence were L90 M (19.7%), M184I/V (44.0%) and K103N/S (32.3%). 2015 AIDS (London, England) Result HIV K103N;K103S;L90M;M184I;M184V 101;101;66;81;81 108;108;71;88;88 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. K101P was above the CI for Portugal and not for DE and V106I below the CI for DE but not Portugal. 2015 AIDS (London, England) Result HIV V106I;K101P 55;0 60;5 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. Mutations M41L (above) and L74I/V (below) were outside the CI for Portugal but not for DE, and T69N (above) and K65R (below) were outside the CI for DE but not for Portugal. 2015 AIDS (London, England) Result HIV K65R;L74I;L74V;M41L;T69N 112;27;27;10;95 116;33;33;14;99 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. SDRMs with highest prevalence in drug-naive patients were L90 M (1.4%) for protease inhibitors, T215Y/F + Rev (Rev = C, D, E, I, S, V) (2.6%) for nucleoside reverse transcriptase inhibitors, (NRTIs) and K103N/S (2.3%) for nonnucleoside reverse transcriptase inhibitors, (NNRTIs). 2015 AIDS (London, England) Result HIV K103N;K103S;L90M;T215F;T215Y 203;203;58;96;96 210;210;63;103;103 NNRTI;NRTI;PR;NNRTI;NRTI;Rev;Rev 222;146;75;271;192;106;111 257;178;83;277;197;109;114 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. A similar finding was observed for T215I positive populations in Individual 3. 2015 PloS one Result HIV T215I 35 40 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Evidence of K103N and T215I minority-level populations were identified in specimens collected 30 and 16 months, respectively, prior to the time point at which resistance was detected by direct sequencing. 2015 PloS one Result HIV K103N;T215I 12;22 17;27 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. However, a K103N-possessing variant persisted at low frequency for nearly 2 years without nevirapine administration and was re-selected when EFV was used (Fig 1A). 2015 PloS one Result HIV K103N 11 16 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In individual 1, K103N was selected during nevirapine treatment and continuously detected for 8 months. 2015 PloS one Result HIV K103N 17 22 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In individual 2, K103N was detected twice by AS-PCR but never became major population (Fig 1B). 2015 PloS one Result HIV K103N 17 22 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In individual 2, K70R was detected as minority population by AS-PCR prior to bulk sequencing and continued to persist for >1000 days. 2015 PloS one Result HIV K70R 17 21 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In individual 3, K70R, K103N and T215I were detected as minority populations by AS-PCR, though not continuously, at least once before these mutations became detectable by bulk sequencing (Fig 1C and S4 Table). 2015 PloS one Result HIV K103N;K70R;T215I 23;17;33 28;21;38 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In individual 4, M184V was detected sporadically as a low-frequency variant after 3TC was withdrawn from their regimen, suggesting a 3TC-selected minority population had persisted around the threshold of AS-PCR detection limit. 2015 PloS one Result HIV M184V 17 22 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In Individual 4, the sequence of the K103N-positive amplicon detected at ID 2 (day 102) was within the cluster of K103N-positive sequences collected at later period ID 9-26 (days >917) (Fig 2C, S5 Table). 2015 PloS one Result HIV K103N;K103N 37;114 42;119 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In individual 5, M184V was detected by AS-PCR nearly 6 months prior to detection by bulk sequencing (Fig 1E). 2015 PloS one Result HIV M184V 17 22 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. In the phylogenetic tree for individual 3, the ID9 (day 957) AS-PCR amplicon (K103N positive) clustered with the K103N bulk sequence at ID 22-24 (days 2046-2117), suggesting that the K103N minority population at ID 9 had high genetic identity to the K103N-positive population that subsequently arose at ID22-24 (Fig 2A, S4 Table). 2015 PloS one Result HIV K103N;K103N;K103N;K103N 78;113;183;250 84;118;188;255 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. K103N and T215I were detected by bulk sequencing soon after the initiation of regimen which included EFV, followed by slight decrease of plasma VL (Fig 1C). 2015 PloS one Result HIV T215I;K103N 10;0 15;5 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. K70R, K103N, M184V and/or T215I were detected at minority levels in 4 of 6 individuals several years prior to detection by bulk sequencing (Individual 2, 3, 4 and 5). 2015 PloS one Result HIV K103N;M184V;T215I;K70R 6;13;26;0 11;18;31;4 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. M41L was also found as minority population in individual 3 by AS-PCR. 2015 PloS one Result HIV M41L 0 4 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Phylogenetic relatedness of majority and minority-level variants with K103N- or T215I. 2015 PloS one Result HIV K103N;T215I 70;80 75;85 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Similar patterns of minority resistance persistence were observed in other individuals; such as Y181C and M184V. 2015 PloS one Result HIV M184V;Y181C 106;96 111;101 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Similarly, in individual 4, K103N was detected as a minority subpopulation 14 months prior to becoming detectable by bulk sequencing. 2015 PloS one Result HIV K103N 28 33 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Two T215I-positive AS-PCR sequences on ID 17(day 1731) and 21 (day 1930) were clustered with ID 25-27 and 31(days 2215-2303, 2552), suggesting their close genetic relationships (Fig 2B, S4 Table). 2015 PloS one Result HIV T215I 4 9 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. However; introducing the D25N mutation had no significant effect on the atomic positions or hydrogen bond interactions when comparing the crystal structures of PR and PRD25N dimers. 2015 Journal of molecular graphics & modelling Result HIV D25N 25 29 PR;PR 160;167 162;169 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Our MD simulations agree with the NMR study showing that the single mutation of D25N altered the dynamic properties of the PR. 2015 Journal of molecular graphics & modelling Result HIV D25N 80 84 PR 123 125 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. Simulations were run on the catalytically active enzyme forms with Asp25 and 25' (PR20MD and PRMD); and on a second set incorporating the active site mutation D25N (PR20D25NMD and PRD25NMD) for comparison with the new crystal structures reported here. 2015 Journal of molecular graphics & modelling Result HIV D25N 159 163 Asp;PR;PR 67;82;180 70;84;182 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. The peaks of correlated motions identified in the MD simulations of wild type PR and PR20 (Figure 7A and 7B) are notably larger than for the corresponding simulations of the inactive mutants incorporating D25N (Figure 7C and 7D). 2015 Journal of molecular graphics & modelling Result HIV D25N 205 209 PR;PR 78;85 80;87 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. While there were ten unique RRDR mutations with subsequent or concurrent evolutionary gain of a putative rifampicin compensatory polymorphism, the vast majority of putative compensatory mutations occurred in association with rpoB S450L (p < 0.001) (S5 Table). 2015 PLoS medicine Result HIV S450L 230 235 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. 22: V106V/A) detected by Sanger sequencing, V106A was identified by UDS at <11%, whereas the K65R could not be confirmed due to insufficient RTP coverage (Tables 2 and 3). 2015 PloS one Result HIV K65R;V106A;V106A;V106V 93;4;44;4 97;11;49;11 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. 28: M184I instead of M184V) (Table 3). 2015 PloS one Result HIV M184I;M184V 4;21 9;26 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. However, in four cases very low proportions of key resistance mutations were detected by UDS: 0.5% K70R (sample No. 2015 PloS one Result HIV K70R 99 103 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Nine resistant variants with the AZT-selected mutations K70R and/or T215I were identified in eight samples at frequencies of 1.0% to 10.0%. 2015 PloS one Result HIV K70R;T215I 56;68 60;73 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Seven 3TC-selected mutations (K65R or M184I) were present in six samples at frequencies of 1.0% to 6.1% (Table 2). 2015 PloS one Result HIV K65R;M184I 30;38 35;43 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. The proportions of K70R quantified by UDS were close to the ASPCR detection limit (0.99% for K70R), whereas the proportions of Y181C quantified by UDS were above the ASPCR detection limit (0.35% for Y181C) (Table 3). 2015 PloS one Result HIV K70R;K70R;Y181C;Y181C 19;93;127;199 23;97;132;204 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Twenty-eight NVP-selected mutations (V90I, K101E, K103N/R, V106A/I/M, V108I, E138A/G/K/R, Y181C, Y188C, G190A or P225H) were detected in 19 samples at levels of 1.1% to 99.1%. 2015 PloS one Result HIV E138A;E138G;E138K;E138R;G190A;K101E;K103N;K103R;P225H;V106A;V106I;V106M;V108I;V90I;Y181C;Y188C 77;77;77;77;104;43;50;50;113;59;59;59;70;37;90;97 88;88;88;88;109;48;57;57;118;68;68;68;75;41;95;102 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Twenty-four HIV-1 resistance mutations were detected in 20 samples by ASPCR: 16x selected by AZT (11x K70R, 4x T215F, 1x T215Y), 6x selected by NVP (5x K103N, 1x Y191C), 2x selected by 3TC (2x M184V), while in 17 samples no key resistance mutations were detected (Tables 1 and 3). 2015 PloS one Result HIV K103N;K70R;M184V;T215F;T215Y;Y191C 152;102;193;111;121;162 157;106;198;116;126;167 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Despite the extensive use of thymidine analogues (TA) like AZT or D4T, TAMs and mutation at codon 151 (Q151M) were not observed. 2015 PloS one Result HIV Q151M 103 108 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Dual-class resistance to NRTIs and NNRTIs were detected in 4 patients with frequent combination of M184V and NNRTI resistance associated mutations. 2015 PloS one Result HIV M184V 99 104 NNRTI;NNRTI;NRTI 35;109;25 41;114;30 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. However, in all the 8 patients, naturally occurring minor mutations/polymorphic changes at PR region (positions M36I, R41K, H69K, L89M, and I93L) were observed. 2015 PloS one Result HIV H69K;I93L;L89M;M36I;R41K 124;140;130;112;118 128;144;134;116;122 PR 91 93 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Other NNRTIs associated mutations Y181S, Y188L, V90I, K101E and G190A were observed in one patient each. 2015 PloS one Result HIV G190A;K101E;V90I;Y181S;Y188L 64;54;48;34;41 69;59;52;39;46 NNRTI 6 12 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. The most frequent NRTIs resistance associated mutations were the lamivudine-induced M184V mutation (n = 4) and K65R (n = 1). 2015 PloS one Result HIV K65R;M184V 111;84 115;89 NRTI 18 23 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. The NNRTIs resistance associated mutations V106M and K103N conferring resistance to EFV and NVP were found in 1 and 2 patient/s, respectively. 2015 PloS one Result HIV K103N;V106M 53;43 58;48 NNRTI 4 10 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. Of these, one mother/infant pair was concordant for K70R; the mother received antenatal ZDV and 7 days of LPV/r study treatment, and the infant was not breast fed. 2014 Journal of AIDS & clinical research Result HIV K70R 52 56 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. The presence of K65R was confirmed in this infant using allele-specific PCR (Table 1). 2014 Journal of AIDS & clinical research Result HIV K65R 16 20 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. The second infant had K65R detected at week 4, after 21 days of maternal study treatment with TDF/FTC; this infant was breast fed. 2014 Journal of AIDS & clinical research Result HIV K65R 22 26 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. As for the protease gene, only one major mutation, L76V, was selected more frequently in non-B subtypes (p = 0.041). 2015 BioMed research international Result HIV L76V 51 55 PR 11 19 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. At the time of the analysis, K103N (p < 0.001) and P225H (p = 0.037) were associated with the first regimen failure, while G190S (p = 0.013) and M230L (p = 0.008) were associated with the second failure. 2015 BioMed research international Result HIV G190S;K103N;M230L;P225H 123;29;145;51 128;34;150;56 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. In contrast, several secondary mutations were found to differ between B and non-B subtypes: L63P (p < 0.001) and A71T (p = 0.021) were higher in subtype B, and M36I (p < 0.001), K20R (p < 0.001), L10V (p = 0.004), L89 M (p < 0.001), and F53L (p = 0.011) were higher in non-B subtypes. 2015 BioMed research international Result HIV A71T;F53L;K20R;L10V;L63P;M36I 113;237;178;196;92;160 117;241;182;200;96;164 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. In the experienced subgroup, at least seven major (M46I, V82A, I54V, L90M, I84V, M46L, and L76V) and 15 accessory mutations (I62V, A71V, L10I, L10V, K20R, L33F, Q58E, K20T, L10F, T74S, F53L, K43T, G73S, I85V, and A71I) developed and were associated with resistance (p < 0.05). 2015 BioMed research international Result HIV A71I;A71V;F53L;G73S;I54V;I62V;I84V;I85V;K20R;K20T;K43T;L10F;L10I;L10V;L33F;L76V;L90M;M46I;M46L;Q58E;T74S;V82A 213;131;185;197;63;125;75;203;149;167;191;173;137;143;155;91;69;51;81;161;179;57 217;135;189;201;67;129;79;207;153;171;195;177;141;147;159;95;73;55;85;165;183;61 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. In the reverse transcriptase gene, the T215F mutation was significantly more selected in non-B subtypes (p = 0.023). 2015 BioMed research international Result HIV T215F 39 44 RT 7 28 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. Taking into account multiple mutations together, the thymidine analog mutations (TAM) pathway 1 (including M41L, L210W, and T215Y) was selected in 40.8% of the patients, whereas TAM-2 (including D67N, K70R, T215F, and 58 K219Q/E) was present in 42.2%. 2015 BioMed research international Result HIV K219Q;D67N;K70R;L210W;M41L;T215F;T215Y 221;195;201;113;107;207;124 228;199;205;118;111;212;129 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. The K103N mutation (40.6%) and P225H mutation (10.6%) were the most prevalent mutations (Figure 1(b)). 2015 BioMed research international Result HIV K103N;P225H 4;31 9;36 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. The M41L, D67N, V118I, L210W, K219Q, and T69D mutations were more prevalent in experienced patients. 2015 BioMed research international Result HIV D67N;K219Q;L210W;M41L;T69D;V118I 10;30;23;4;41;16 14;35;28;8;45;21 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. The most prevalent major PI mutations were as follows: M46I (21%), V82A (17%), I54V (16.4%), L90M (13.5%), I50L (8.2%), I84V (5.8%), D30N 22 (5.8%), and M46L (5%) (Figure 1(c)). 2015 BioMed research international Result HIV D30N;I50L;I54V;I84V;L90M;M46I;M46L;V82A 133;107;79;120;93;55;153;67 137;111;83;124;97;59;157;71 PI 25 27 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. The most prevalent mutations related to NRTIs were M184V (80.1%), followed by M41L (31.8%), T215Y (30.2%), D67N (25.5%), K70R (24.4%), T215F (18.3%), L210W (15.1%), and V118I (15.1%) (Figure 1(a)). 2015 BioMed research international Result HIV D67N;K70R;L210W;M184V;M41L;T215F;T215Y;V118I 107;121;150;51;78;135;92;169 111;125;155;56;82;140;97;174 NRTI 40 45 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. With respect to accessory or secondary mutations, the most frequent were L63P (60.7%), M36I (41.1%), I93L (40.1%), I62V (39%), V77I (35.8%), A71V (24.9%), and L10I (24.7%) (Figure 1(d)). 2015 BioMed research international Result HIV A71V;I62V;I93L;L10I;L63P;M36I;V77I 141;115;101;159;73;87;127 145;119;105;163;77;91;131 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. All the viruses in the cluster carried the G190A mutation (Fig 1A). 2015 PloS one Result HIV G190A 43 48 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. E138GAR mutations, conferring DR to rilpivirine and etravirine were also highly prevalent (4.7%), causing higher PDR estimations when using the Stanford DR definition (Table 3). 2015 PloS one Result HIV E138A;E138G;E138R 0;0;0 7;7;7 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. M184V (71.4%, <48 months; 67.8%, >=48 months), and K103N (50.0%, <48 months; 41.7%, >=48 months) were the most frequent ADR mutations (Table 3). 2015 PloS one Result HIV K103N;M184V 51;0 56;5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Only M46IL was more frequent in recently infected individuals (p = 0.0240, Fig 2). 2015 PloS one Result HIV M46I;M46L 5;5 10;10 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. The first case included a virus with acquired K103N from a heterosexual male enrolled at Tegucigalpa and a female with transmitted K103N from San Pedro Sula (Fig 1B); the second case included two females enrolled at San Pedro Sula, one with acquired K103N and the other with transmitted K103N (Fig 1C); and the third case included two closely related, multidrug resistant viruses from heterosexual males enrolled at La Ceiba, one containing acquired M46L and T215Y and the other containing transmitted M46 and T215S (Fig 1D). 2015 PloS one Result HIV K103N;K103N;K103N;K103N;M46L;T215S;T215Y 46;131;250;287;450;510;459 51;136;255;292;454;515;464 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. The lack of correlation for NRTI PDR and ADR remained even after excluding M184V from the analysis. 2015 PloS one Result HIV M184V 75 80 NRTI 28 32 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. The most prevalent PDR mutations were M46IL (1.4%) to PI, T215 revertants (0.5%) to NRTI, and K103NS (5.6%) to NNRTI. 2015 PloS one Result HIV K103N;K103S;M46I;M46L 94;94;38;38 100;100;43;43 NNRTI;NRTI;PI 111;84;54 116;88;56 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. 81.25 % (n = 13) had more than 1 NNRTI mutation.Y181C and G190A was the most common NNRTI mutation present in 37.5 % (n = 6) patient each. 2015 BMC infectious diseases Result HIV G190A;Y181C 58;48 63;53 NNRTI;NNRTI 33;84 38;89 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. Among PI mutations, M46I (n = 5) was the commonest mutation, followed by N88S (n = 3), I50L (n = 2), I84V (n = 2), V 82A (n = 1). 2015 BMC infectious diseases Result HIV I50L;I84V;M46I;N88S;V82A 87;101;20;73;115 91;105;24;77;120 PI 6 8 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. M184V was the commonest NRTI mutation and was present in 13 out of 16 patients. 2015 BMC infectious diseases Result HIV M184V 0 5 NRTI 24 28 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. 1c), T215Y was the earliest NRTI mutation to emerge in plasma in the 15th month of therapy, followed by M41L and then by E44D. 2015 Virology journal Result HIV E44D;M41L;T215Y 121;104;5 125;108;10 NRTI 28 32 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. And by the following visit, virus K103N/Y181C/H221Y was associated the same percentage. 2015 Virology journal Result HIV H221Y;K103N;Y181C 46;34;40 51;39;45 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. As shown in Table 1, virusT215Y/V179E/Y181C/H221Y, the recombined patient-derived HIV-1 RT fragment, did not exhibit a significant increase with respect to AZT resistance, but did exhibit higher levels of resistance to EFV (up to 5.57-fold). 2015 Virology journal Result HIV H221Y;V179E;Y181C 44;32;38 49;37;43 RT 88 90 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. For EFV, the IC50 for virus with the T215Y/V179E mutation was higher than with T215Y/K103N, suggesting that the background factor affected the IC50 significantly (F = 93.10, P < 0.0001). 2015 Virology journal Result HIV K103N;T215Y;T215Y;V179E 85;37;79;43 90;42;84;48 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. H221Y did not affect the IC50 of three NRTIs (AZT, 3TC, and d4T). 2015 Virology journal Result HIV H221Y 0 5 NRTI 39 44 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. H221Y emerged with a low mutation percentage (19.20 %). 2015 Virology journal Result HIV H221Y 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. However, E44A replaced E44D as the last pattern of mutation with respect to M41L/T215Y. 2015 Virology journal Result HIV E44A;E44D;M41L;T215Y 9;23;76;81 13;27;80;86 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. However, the IC50 for virus incorporating Y181C was higher than the others without Y181C with respect to AZT and 3TC (P < 0.0001 and P = 0.0010); while Y181C did not increase the IC50 of d4T (F = 4.99, P = 0.0719). 2015 Virology journal Result HIV Y181C;Y181C;Y181C 42;83;152 47;88;157 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. However, when H221Y was reversed (T215Y/K103N/Y181C), only the IC50 of EFV was observed to significantly increase to 122.07 +- 12.24 nM (8.19-fold, p < 0.01), although this was lower than the 503.47 +- 207.80 nM (33.79-fold). 2015 Virology journal Result HIV K103N;T215Y;Y181C;H221Y 40;34;46;14 45;39;51;19 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In a T215Y/K103N background, neither H221Y nor Y181C expressed significant changes in EFV resistance (F = 0.12, P = 0.7404 and F = 4.24, P = 0.0736), but the interaction between 181 and 221 was statistically significant (F = 38.12, P = 0.0003). 2015 Virology journal Result HIV H221Y;K103N;T215Y;Y181C 37;11;5;47 42;16;10;52 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In PBMCs, it was M41L/E44D/T215Y that was first detected in the 25th month; with E44A replacing E44D completely by the following visit, and M41L/E44A/T215Y was the last NRTI mutation pattern to be observed. 2015 Virology journal Result HIV E44A;E44D;M41L;M41L;T215Y;T215Y;E44A;E44D 145;22;17;140;27;150;81;96 149;26;21;144;32;155;85;100 NRTI 169 173 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In PBMCs, Y181C combined with H221Y to emerge in the 25th month and this then remained stable. 2015 Virology journal Result HIV H221Y;Y181C 30;10 35;15 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In plasma, Y181C emerged in the 7th month, followed by H221Y with 100 % mutation in the 15th month. 2015 Virology journal Result HIV H221Y;Y181C 55;11 60;16 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Regarding T215Y/V179E as the background, Y181C expressed significant increases in EFV resistance, but H221Y did not. 2015 Virology journal Result HIV H221Y;T215Y;V179E;Y181C 102;10;16;41 107;15;21;46 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. T215Y, K103N, and Y181C were detected in plasma with 100 % observed by the 30th month. 2015 Virology journal Result HIV K103N;Y181C;T215Y 7;18;0 12;23;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. T215Y/V179E-containing virus resulted in a dramatic 20.20-fold increase in AZT resistance (p < 0.01), and a second increase in 3TC and d4T (P < 0.05). 2015 Virology journal Result HIV V179E;T215Y 6;0 11;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. The IC50 of different drugs for another triple-mutation, T215Y/V179E/H221Y, presented an effect similar to that with T215Y/V179E/Y181C, but at a different level of significance. 2015 Virology journal Result HIV H221Y;T215Y;T215Y;V179E;V179E;Y181C 69;57;117;63;123;129 74;62;122;68;128;134 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. The last stable mutation pattern observed in both patients' plasma and in PBMCs was the double-mutation Y181C/H221Y, along with others. 2015 Virology journal Result HIV H221Y;Y181C 110;104 115;109 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Two mutation patterns, both V179D and V179E, were observed in plasma and PBMCs. 2015 Virology journal Result HIV V179D;V179E 28;38 33;43 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. V179D first emerged in PBMCs in the 7th month, with only 12.5 %. 2015 Virology journal Result HIV V179D 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. V179D was found in plasma from the first month; however, V179E began to replace V179D in the 25th month and completely replaced V179D in the 49th month. 2015 Virology journal Result HIV V179D;V179D;V179E;V179D 80;128;57;0 85;133;62;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. V179E emerged in the 25th month and completely replaced V179D in the 31st month. 2015 Virology journal Result HIV V179D;V179E 56;0 61;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Virus with a triple-mutation of T215Y/V179E/Y181C manifested an observed increase in AZT, 3TC, and d4T resistance (p < 0.05). 2015 Virology journal Result HIV T215Y;V179E;Y181C 32;38;44 37;43;49 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. VirusT215Y/K103N/Y181C/H221Y, the HIV-1 RT fragment from patient 2, exhibited dramatic increases in IC50 with respect to all the four agents (AZT, 53.94-fold; EFV, 33.79-fold; 3TC, 31.72-fold; d4T, 37.72-fold; p < 0.01). 2015 Virology journal Result HIV H221Y;K103N;Y181C 23;11;17 28;16;22 RT 40 42 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. We obtained eight recombinant viruses: T215Y/V179E/H221Y/Y181C, T215Y/V179E/Y181C, T215Y/V179E/H221Y, T215Y/V179E, T215Y/K103N/H221Y/Y181C, T215Y/K103N/Y181C, T215Y/K103N/H221Y, and T215Y/K103N. 2015 Virology journal Result HIV H221Y;H221Y;H221Y;H221Y;K103N;K103N;K103N;T215Y;T215Y;T215Y;T215Y;T215Y;T215Y;V179E;V179E;V179E;Y181C;Y181C;Y181C;Y181C;K103N;T215Y;T215Y;V179E 51;95;127;171;121;146;165;39;64;83;115;140;159;45;70;89;57;76;133;152;188;102;182;108 56;100;132;176;126;151;170;44;69;88;120;145;164;50;75;94;62;81;138;157;193;107;187;113 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. When we added H221Y, the T215Y/K103N virus significantly increased its AZT and 3TC resistance. 2015 Virology journal Result HIV H221Y;K103N;T215Y 14;31;25 19;36;30 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. Among those with M184V and viremia the mean decline in CD4 count was 2.5 cells/mm3/year (95% CI: -14, 9.0) compared to a decline of 14 cells/mm3/year (95% CI: -24, -4.1) in those without M184V (p-value for difference 0.1; Figure). 2016 Tropical medicine & international health Result HIV M184V;M184V 17;187 22;192 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. The median time from ART initiation to resistance testing was 17 months (IQR: 10, 29) and the median time from first HIV RNA >1000 copies/mL to resistance testing was 0 months (IQR: 0, 3.3); 308 (88%) of HIV drug resistance tests came from the first visit with an HIV RNA >1000 copies/mL; 151 (43%) had the M184V mutation while 220 (63%) had any NNRTI resistance, 117 (33%) of whom had the K103N mutation; 14 (4%) had thymidine analogue mutations (TAMs). 2016 Tropical medicine & international health Result HIV K103N;M184V 390;307 395;312 NNRTI 346 351 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. There was no association between obtaining the resistance test at either the first detected viremia (164 patients) or a subsequent point during sustained viremia (186 patients) and HIV drug resistance (Chi square p=0.4 for M184V and p=0.6 for NNRTI mutations). 2016 Tropical medicine & international health Result HIV M184V 223 228 NNRTI 243 248 26584666 CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. When associating HIV drug resistance with immunologic failure among the 350 patients, only 51 of 151(34%), with the M184V mutation reached immunologic failure criteria compared to 90 of 199 (45%) without M184V (Chi square p=0.03). 2016 Tropical medicine & international health Result HIV M184V;M184V 116;204 121;209 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. Also, the substitution S411G only induced a 2- fold increase in 882376 IC50 and had no impact on NBD-556 and BMS-378806 IC50s. 2015 Bioorganic & medicinal chemistry Result HIV S411G 23 28 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. As expected, our results indicated that these mutations induced resistance to 200 nM BMS-378806 and only the M475I induced resistance to NBD-556 but both mutants showed marginal resistance to 882376 (about 3-fold). 2015 Bioorganic & medicinal chemistry Result HIV M475I 109 114 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. As reported in Table 4, we observed that the K348R substitution had virtually no effect on antiviral activity as indicated by the low IC50 detected that was similar to the IC50 obtained for the HIV-1HXB2 WT. 2015 Bioorganic & medicinal chemistry Result HIV K348R 45 50 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. By contrast, we identified 5 amino acids substitutions in the sample obtained from the culture grown in the presence of 33 muM of 882376 (Table 3): K348R located in the C3 that was different (K348E) in the sample from the 25 muM culture; S411G located in the V4; K432E located in the CD4 binding site; C604Y located in the immunodominant region of gp41 and C764R also located in the gp41 (Table 3). 2015 Bioorganic & medicinal chemistry Result HIV C604Y;C764R;K348E;K348R;K432E;S411G 302;357;192;148;263;238 307;362;197;153;268;243 gp41;gp41 348;383 352;387 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. By contrast, we observed that the amino acid substitution detected in the CD4 binding region K432E conferred resistance not only to 882376 which exhibited an IC50 >=25, about 6-fold the IC50 obtained for the HIV-1HXB2 WT but also to NBD-556 and BMS-378806. 2015 Bioorganic & medicinal chemistry Result HIV K432E 93 98 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. Moreover, one of the two substitutions detected in the gp41 region, C764R conferred about 3-fold increase of the IC50 of 882376 while the C604Y substitution detected in the highly conserved immunodominant region produced non-infectious virus when expressed as a single mutation. 2015 Bioorganic & medicinal chemistry Result HIV C604Y;C764R 138;68 143;73 gp41 55 59 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. The substitution of Cysteine 604 with Tyrosine (C604Y) in the unprocessed gp160 disrupts the gp41 disulfide loop (C598/C604) which has been reported to be critical to the cellular protease furin recognition site of gp160 therefore, impedes the processing of gp160 resulting in non-infectious viral particles. 2015 Bioorganic & medicinal chemistry Result HIV C604Y;C604Y 48;20 53;46 PR;gp160;gp160;gp160;gp41 180;74;215;259;93 188;79;220;264;97 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. To better understand the binding site of 882376 we also investigated its inhibitory activity against pseudoviruses carrying the S375H or S375Y mutation located in the Phe43 cavity. 2015 Bioorganic & medicinal chemistry Result HIV S375H;S375Y 128;137 133;142 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. We detected one amino acid substitution, K348E (frequency 1/7) in the sample obtained from the culture grown in the presence of 25 muM of 882376. 2015 Bioorganic & medicinal chemistry Result HIV K348E 41 46 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. We selected the mutations that conferred the highest resistance of HIV-1LAI to BMS-378806, the two single mutations M475I and M434I. 2015 Bioorganic & medicinal chemistry Result HIV M434I;M475I 126;116 131;121 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. When substitutions S411G and K432E were combined we noticed a slightly increase in viral infectivity suggesting that these amino acid substitutions may be rescuing the virus (data not shown). 2015 Bioorganic & medicinal chemistry Result HIV K432E;S411G 29;19 34;24 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. 7F), the W252A mutant HIV-1 made less early DNA than wild type HIV-1, in agreement with previous experiments. 2015 PLoS pathogens Result HIV W252A 9 14 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. A reduced interaction of eEF1A with RT W252A and L303A was further confirmed using BLI assay. 2015 PLoS pathogens Result HIV L303A;W252A 49;39 54;44 RT 36 38 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. As expected, replication of the W252A RT virus was much weaker than wild type in Jurkat cells (Fig 4E and 4F). 2015 PLoS pathogens Result HIV W252A 32 37 RT 38 40 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. As L303A and W252A RT mutation have similar affect on interaction with eEF1A, W252A was selected for use in further experiments. 2015 PLoS pathogens Result HIV L303A;W252A;W252A 3;13;78 8;18;83 RT 19 21 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. As previously reported, L234A had a significant reduction of the signal indicating this mutation negatively affect RT dimerization thus validating the system. 2015 PLoS pathogens Result HIV L234A 24 29 RT 115 117 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Did B induces instability of the wild type but not W252A mutant reverse transcription complex. 2015 PLoS pathogens Result HIV W252A 51 56 RT 64 85 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Hence a W252A RT mutation can down regulate both RT activity and the interaction between eEF1A and RT. 2015 PLoS pathogens Result HIV W252A 8 13 RT;RT;RT 14;49;99 16;51;101 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. However, Did B had no dramatic effect on the W252A mutant HIV-1 CA or viral DNA levels in any fraction (Fig 7D and 7F, red vs. 2015 PLoS pathogens Result HIV W252A 45 50 Capsid 64 66 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. In contrast, mutation T253A reveals no adverse effect on protein stability. 2015 PLoS pathogens Result HIV T253A 22 27 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. In order to assess the effect of the W252A mutation on RT heterodimerization, a mammalian protein-protein interaction trap (MAPPIT) assay was undertaken (S6 Fig). 2015 PLoS pathogens Result HIV W252A 37 42 RT 55 57 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Similar experiments were performed here using equivalent amounts of wild type or W252A virus, normalized to CA, to infect TZM-bl cells. 2015 PLoS pathogens Result HIV W252A 81 86 Capsid 108 110 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Single alanine substitutions at residues W252 or T253 were further evaluated and the W252A mutation significantly inhibited co-IP of RT with eEF1A, while the effect of the T253A mutation was minor compared to co-IP of wild type RT (Fig 2G). 2015 PLoS pathogens Result HIV T253A;W252A 172;85 177;90 RT;RT 133;228 135;230 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Structurally, the W252A mutation is located within the loop region that links the palm domain to the thumb domain, proximal to the first alpha-helix of the thumb domain, but distal to the inter-subunit interface (S4 Fig). 2015 PLoS pathogens Result HIV W252A 18 23 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The combined results suggest that the W252A RT mutation affects late DNA synthesis due to changes in the RT-eEF1A interaction rather than due to reduced RT activity per se, and this significantly reduced HIV-1 replication. 2015 PLoS pathogens Result HIV W252A 38 43 RT;RT;RT 44;105;153 46;107;155 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The eEF1A biosensors were incubated in bacterially produced 6xhis recombinant wild type RTp66 at 90, 30 and 10 nM, or mutant RTp66 W252A and L303A RT at 90 nM (Fig 3E; S5A and S5B Fig). 2015 PLoS pathogens Result HIV L303A 141 146 RT;RT;RT 88;125;147 90;127;149 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The effect of a W252A RT mutation on reverse transcription efficiency was assessed in infected cells. 2015 PLoS pathogens Result HIV W252A 16 21 RT;RT 37;22 58;24 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The HIV-1 wild-type and W252A RT mutant proviral plasmids were transfected into HEK293T cells, along with a control plasmid pCMV-Gluc2, and cell lysates and culture supernatants were collected at 48 h post-transfection. 2015 PLoS pathogens Result HIV W252A 24 29 RT 30 32 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The number of foci was significantly reduced in cells infected by W252A RT virus compared with wild type virus (p <0.05; Fig 5A), indicating a reduced association of W252A RT with eEF1A. 2015 PLoS pathogens Result HIV W252A;W252A 66;166 71;171 RT;RT 72;172 74;174 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The PLA data correlate to decreased association of W252A RT with eEF1A as observed in the co-IP assays (Fig 2G) and provide further evidence that a W252A mutation in RT impairs its interaction with eEF1A. 2015 PLoS pathogens Result HIV W252A;W252A 51;148 56;153 RT;RT 57;166 59;168 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The predicted reduced stability of W252A could therefore have consequences on protein conformation that could in turn impact on RT:eEF1A interaction. 2015 PLoS pathogens Result HIV W252A 35 40 RT 128 130 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The results show that a W252A RT mutation reduced the level of RT activity by ~50% (Fig 4D). 2015 PLoS pathogens Result HIV W252A 24 29 RT;RT 30;63 32;65 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The results therefore indicate that W252A imparts only a localized effect on structure stability. 2015 PLoS pathogens Result HIV W252A 36 41 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The thumb domain plays a role during reverse transcription to help properly position the viral nucleic acid through interactions that involve both the primer and template strands, so a W252A mutation could affect RT activity. 2015 PLoS pathogens Result HIV W252A 185 190 RT;RT 37;213 58;215 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A and T253A mutations did not affect luciferase expression indicating that heterodimerization between R p51 and RT p66 harboring mutations were not affected. 2015 PLoS pathogens Result HIV T253A;W252A 14;4 19;9 RT 120 122 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A mutant reverse transcription efficiency was ~12-13% in either the presence or absence of 0.8 nM Did B (Table 4). 2015 PLoS pathogens Result HIV W252A 4 9 RT 17 38 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A mutation is important for RT structure but does not impair heterodimer formation. 2015 PLoS pathogens Result HIV W252A 4 9 RT 36 38 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A mutation regulates reverse transcription in vitro . 2015 PLoS pathogens Result HIV W252A 4 9 RT 29 50 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A mutation regulates reverse transcription in vitro. 2015 PLoS pathogens Result HIV W252A 4 9 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A RT mutation affects late steps of reverse transcription and virus replication. 2015 PLoS pathogens Result HIV W252A 4 9 RT;RT 44;10 65;12 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A RT mutation significantly reduced the association of RT with eEF1A in infected cells. 2015 PLoS pathogens Result HIV W252A 4 9 RT;RT 10;63 12;65 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Thermodynamic stability calculations using the empirical forcefield FoldX program show that the mutation W252A severely destabilizes structure in both individual subunits and within the heterodimer (DeltaDeltaG of mutations range between ~4.7-5.3 kcal/mol) (Table 2). 2015 PLoS pathogens Result HIV W252A 105 110 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. To test the effect of Did B on RTCs and reverse transcription, large scale infections of HEK293T cells were performed using VSV-G pseudotyped wild type and W252A mutant HIV-1. 2015 PLoS pathogens Result HIV W252A 156 161 RT 40 61 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. To test this hypothesis, equal amounts of wild type or W252A RT mutant virus, normalized to CA levels, were used in a standard in vitro RT assay. 2015 PLoS pathogens Result HIV W252A 55 60 Capsid;RT;RT 92;61;136 94;63;138 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. To test this possibility further, wild type RTp51 or p51 with the single mutations L295A, T296A, L301A, and L303A were subjected to co-IP analysis as previously described. 2015 PLoS pathogens Result HIV L295A;L301A;L303A;T296A 83;97;108;90 88;102;113;95 RT 44 46 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Using an HIV-1NL4.3 proviral DNA plasmid, the RT W252A mutation was introduced in pol so that infectious virus could be produced. 2015 PLoS pathogens Result HIV W252A 49 54 Pol;RT 82;46 85;48 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Virus particle production of the W252A RT mutant in culture supernatant was slightly reduced compared to wild type virus (Fig 4B). 2015 PLoS pathogens Result HIV W252A 33 38 RT 39 41 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Western blot of partially purified virions using an anti-HIV-1 polyclonal antibody or an anti-RT antibody showed similar protein staining patterns of viral proteins and RT (Fig 4C), suggesting that an W252A RT mutation did not significantly affect Gag-Pol steady-state levels or its cleavage by HIV-1 protease. 2015 PLoS pathogens Result HIV W252A 201 206 PR;GagPol;RT;RT;RT 301;248;94;169;207 309;255;96;171;209 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. When the amount of virus used for infection was normalized to total RT activity, thereby increasing the input of W252A RT mutant virus relative to wild type, the level of early DNA made by the W252A RT virus was proportionally increased, but the relative efficiency of reverse transcription remained low compared to wild type HIV-1 (Table 3). 2015 PLoS pathogens Result HIV W252A;W252A 113;193 118;198 RT;RT;RT;RT 269;68;119;199 290;70;121;201 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. When the infections were normalized to CA, the W252A RT mutant virus produced early viral DNA at levels slight lower than wild type virus (p > 0.05; Table 3), but the levels of late viral DNA made by the W252A RT mutant virus was significantly reduced (p < 0.05). 2015 PLoS pathogens Result HIV W252A;W252A 47;204 52;209 Capsid;RT;RT 39;53;210 41;55;212 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. While the interaction between eEF1A and L295A, T296A and L301A were comparable to wild type RT, the L303A mutant, like W252A, interacted poorly with eEF1A (Fig 3C), which likely accounts for the reduction in interaction of the 299-303A amino acid mutations with eEF1A. 2015 PLoS pathogens Result HIV L295A;L301A;L303A;T296A;W252A 40;57;100;47;119 45;62;105;52;124 RT 92 94 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. A subtype C-specific polymorphism associated with NRTIs (V118I) was detected in one patient. 2015 Journal of translational medicine Result HIV V118I 57 62 NRTI 50 55 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. As previously reported in this group of well characterized patients, two patients had NNRTI associated mutations (G190A and E138G) and one patient had a NRTI resistance-associated mutation (L210 W). 2015 Journal of translational medicine Result HIV E138G;G190A;L210W 124;114;190 129;120;196 NNRTI;NRTI 86;153 91;157 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. Two polymorphic minor INI-accessory mutations (V201I and I203 M) occurred in 82.2 and 13.3 % of the patients, respectively. 2015 Journal of translational medicine Result HIV I203M;V201I 57;47 63;53 IN 22 25 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. Further statistical analysis was also performed to complete the linear correlation analysis of data showing non-normal distribution, which revealed that there are no significant differences between the values determined by the different assays (p > 0.05) (wild-type: z = 1.35 and p = 0.22; I54M/L90M mutant: z = 0.51 and p = 0.69). 2015 Viruses Result HIV I54M;L90M 290;295 294;299 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. Introduction of the double mutation I54M and L90M greatly decreased the efficacy of the inhibitors, with the exception of tipranavir, which remained indifferent to the mutations. 2015 Viruses Result HIV I54M;L90M 36;45 40;49 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. L90M exerts little or no effect on the susceptibility to tipranavir in HIV-1 isolates, while I54M was associated with a reduced susceptibility to the inhibitor. 2015 Viruses Result HIV I54M;L90M 93;0 97;4 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. The I54M-L90M double mutation resulted in >40 fold and >20 fold increase in IC50 in case of darunavir and lopinavir, respectively, and IC50 of indinavir sulfate increased by >10 fold. 2015 Viruses Result HIV I54M;L90M 4;9 8;13 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. A higher prevalence of E138A was also observed in subtype F1-infected patients from Portugal (7.1%), explaining that low proportion of patients scored susceptible (92.0% +- 0.0%). 2016 AIDS research and human retroviruses Result HIV E138A 23 28 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. A variable prevalence of minor RPV-RAMs was observed, with minor RPV-RAMs V90I, A98G, V106I, and V179D/E/I/T differing significantly across subtypes, when corrected for multiple testing. 2016 AIDS research and human retroviruses Result HIV A98G;V106I;V179D;V179E;V179I;V179T;V90I 80;86;97;97;97;97;74 84;91;108;108;108;108;78 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Evidence of transmitted drug resistance was observed in 401 patients (8.7%), with RPV-RAMs Y181C, Y188L, K103S, V106A, V179F, and G190A/S detected as SDRMs. 2016 AIDS research and human retroviruses Result HIV G190A;G190S;K103S;V106A;V179F;Y181C;Y188L 130;130;105;112;119;91;98 137;137;110;117;124;96;103 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Major signature NRTI mutations against TDF and FTC M184V (0.8%, n = 35), M184I (0.07%, n = 3), K65R (0.07%, n = 3), and K70E (0.04%, n = 2) were rarely observed. 2016 AIDS research and human retroviruses Result HIV K65R;K70E;M184I;M184V 95;120;73;51 99;124;78;56 NRTI 16 20 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Minor RPV-RAMs V179I (5.7%, n = 266), V106I (4.9%, n = 227), and V90I (3.0%, n = 137) occurred most. 2016 AIDS research and human retroviruses Result HIV V106I;V179I;V90I 38;15;65 43;20;69 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Phylogenetic analysis of the 1,121 subtype C-infected patient population revealed that a large number of Portuguese treatment-naive patients with E138A formed a monophyletic cluster. 2016 AIDS research and human retroviruses Result HIV E138A 146 151 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. RPV susceptibility in subtype C-infected patients differed according to geographic origin of sampling, with 84.3% +- 1.1% of patients from Portugal who scored susceptible compared to 95.0% +- 0.0% of patients from Belgium (Table 1), which was largely explained by a prevalence of RPV-RAM E138A of, respectively, 13.2% and 5.0% (p = .044). 2016 AIDS research and human retroviruses Result HIV E138A 288 293 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Strikingly, among 116 subtype C-infected treatment-experienced patients from Portugal, the RPV-RAM E138A could be detected in 11 patients (9.5%), compared to 35 treatment-naive patients (13.2%), resulting into a transmission ratio of 1.39. 2016 AIDS research and human retroviruses Result HIV E138A 99 104 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Subtype F1-infected patients from Belgium however lacked E138A, but they still displayed a lower average susceptibility score (82.5% +- 30.1%) mainly attributable to the minor RVP-RAM A98G (52.6%). 2016 AIDS research and human retroviruses Result HIV A98G;E138A 184;57 188;62 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. The frequency of major RPV-RAM E138A in this population was 3.1% compared to 4.2% in the patient population with SDRMs, although strongly varying according to geography and subtype (Table 2). 2016 AIDS research and human retroviruses Result HIV E138A 31 36 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. The highest prevalence of major RPV-RAMs was observed for subtypes C (12.5%) and F1 (6.8%), largely explained by the subtype-specific occurrence of E138A with, respectively, 11.3% and 6.1% (Table 1). 2016 AIDS research and human retroviruses Result HIV E138A 148 153 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. The most prevalent major RPV-RAM was E138A (3.2%, n = 146), occurring in 69% of all patients with >=1 major RPV-RAM, followed by K101E (0.5%, n = 24). 2016 AIDS research and human retroviruses Result HIV E138A;K101E 37;129 42;134 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. Twenty separate phylogenetic analyses, each containing a subsample of 200 patients of the initial dataset, demonstrated a consistent monophyletic grouping of this E138A cluster among all 20 ML trees (100%), with an aLRT support for this cluster above 0.8 in 16 trees (80%) (Data not shown). 2016 AIDS research and human retroviruses Result HIV E138A 163 168 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. From this it becomes evident that the otherwise resistant K20T mutation has the potential to reduce the resistance of TPM in comparison to DBM (Figure 4F, 5F). 2015 BMC bioinformatics Result HIV K20T 58 62 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. L33F mutation caused positional change of neighboring residue Glu34, which resulted in formation of an extra hydrogen bond between Glu34 and Lys20 in DBM. 2015 BMC bioinformatics Result HIV L33F 0 4 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. Possible intra-molecular interactions by V77I, L33F, K20T and the neighboring residues, and their effect on cavity size. 2015 BMC bioinformatics Result HIV K20T;L33F;V77I 53;47;41 57;51;45 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. The mutants of this protease structure are abbreviated as DBM_M (V77I, L33F) and TPM_M (V77I, L33F, and K20T). 2015 BMC bioinformatics Result HIV K20T;L33F;L33F;V77I;V77I 104;71;94;65;88 108;75;98;69;92 PR 20 28 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. The score representing probability of binding and presenting of the peptide by HLA-A3 was seen to be decreased to a small extent, suggesting that the emergence of mutation V77I is preferentially due to selective pressures imposed by anti-viral therapy, and less likely due to immunological pressure. 2015 BMC bioinformatics Result HIV V77I 172 176 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. This is also credible in case of V77I mutation as it is located as an anchoring residue in the epitope recognized by HLA-A3, (nonamer-LIGPTPVNI). 2015 BMC bioinformatics Result HIV V77I 33 37 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. To study the effect of V77I mutation along with L33F and K20T on the flap movements of HIV protease, we considered the semi open modeled structure of HIV-1PR (PDB:1HVP). 2015 BMC bioinformatics Result HIV K20T;L33F;V77I 57;48;23 61;52;27 PR 91 99 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. V77I mutation in combination with L33F (DBM) displayed increase in the size of binding cavity (representative structure) with volume and area as 1375.5 A3 and 732.10 A2 respectively. 2015 BMC bioinformatics Result HIV L33F;V77I 34;0 38;4 26700639 Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C and 48.6% (54.8%, if those not on Tenofovir are excluded) had K65R mutations. 2015 PloS one Result HIV K65R;M184I;M184V;Y181C 132;49;49;64 136;56;56;69 26700639 Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda. The most common NRTI- associated mutation was M184V (33.3%) out of the 15 NRTI mutations, whereas K103N and Y181C NNRTI mutations occurred at a frequency of 35.0% and 25.0% respectively (n = 20). 2015 PloS one Result HIV K103N;M184V;Y181C 98;46;108 103;51;113 NNRTI;NRTI;NRTI 114;16;74 119;20;78 26700639 Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda. There were three PI accessory mutations identified, two I85V and one F53L. 2015 PloS one Result HIV F53L;I85V 69;56 73;60 PI 17 19 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. Finally, several polymorphic sites were identified, with L63PSA being the most prevalent (96% of cases). 2015 HIV/AIDS (Auckland, N.Z.) Result HIV L63A;L63P;L63S 57;57;57 63;63;63 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. Less frequent substitutions identified in the subtype-A1 sequences of the study group involved I15V, G16E, R41K, K45R, and K70R (<60% of cases). 2015 HIV/AIDS (Auckland, N.Z.) Result HIV G16E;I15V;K45R;K70R;R41K 101;95;113;123;107 105;99;117;127;111 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. Specifically, the E35D and M36I substitutions were present in 100% of cases, followed by substitutions H69K (99%), I13V (96%), L89M (95%), and R57K (93%), indicating that these sequence alterations may occur as genetic signatures in subtype A1. 2015 HIV/AIDS (Auckland, N.Z.) Result HIV E35D;H69K;I13V;L89M;M36I;R57K 18;103;115;127;27;143 22;107;119;131;31;147 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. The 22 cases experiencing virologic failure presented with the following DRMs: M46I, F53LY, I54LTV, G73ST, L76V, V82AT, I84V, I185V, N88D, and L90M for PIs; L100I, K103NS, V179F Y181C, G190AS, V106A, K103N, and P225H for NNRTIs; and M41L, K65R, D67GN, T69D, K70ER, L74V, Y115F, F116Y, Q151M, M184V, L210W, T215CDFIY, and K219EQR for NRTIs. 2015 HIV/AIDS (Auckland, N.Z.) Result HIV D67G;D67N;F116Y;F53L;F53Y;G190A;G190S;G73S;G73T;I185V;I54L;I54T;I54V;I84V;K103N;K103N;K103S;K219E;K219Q;K219R;K65R;K70E;K70R;L100I;L210W;L74V;L76V;L90M;M184V;M41L;M46I;N88D;P225H;Q151M;T215C;T215D;T215F;T215I;T215Y;T69D;V106A;V179F;V82A;V82T;Y115F;Y181C 245;245;278;85;85;185;185;100;100;126;92;92;92;120;164;200;164;321;321;321;239;258;258;157;299;265;107;143;292;233;79;133;211;285;306;306;306;306;306;252;193;172;113;113;271;178 250;250;283;90;90;191;191;105;105;131;98;98;98;124;170;205;170;328;328;328;243;263;263;162;304;269;111;147;297;237;83;137;216;290;315;315;315;315;315;256;198;177;118;118;276;183 NNRTI;NRTI;PI 221;333;152 227;338;155 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. The four treatment-naive cases presented with the following DRMs: I84V for PIs, K103N for NNRTIs, and T215S and K219Q for NRTIs. 2015 HIV/AIDS (Auckland, N.Z.) Result HIV I84V;K103N;K219Q;T215S 66;80;112;102 70;85;117;107 NNRTI;NRTI;PI 90;122;75 96;127;78 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. The most common DRM for each antiretroviral agent was M184V for NRTIs (79%), K103N for NNRTIs (56%), and M46I and I54V for PIs (75%). 2015 HIV/AIDS (Auckland, N.Z.) Result HIV I54V;K103N;M184V;M46I 114;77;54;105 118;82;59;109 NNRTI;NRTI;PI 87;64;123 93;69;126 26715861 HIV-1 subtype characteristics of infected persons living in southwestern Greece. This involved six protease amino acid substitutions (I13V, E35D, M36I, R57K, H69K, and L89M), which are drug-resistance support mutations in subtype B. 2015 HIV/AIDS (Auckland, N.Z.) Result HIV E35D;H69K;I13V;L89M;M36I;R57K 59;77;53;87;65;71 63;81;57;91;69;75 PR 18 26 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. A98G and K101E were the most common non-major transmitted NNRTI DRMs. 2015 PloS one Result HIV K101E;A98G 9;0 14;4 NNRTI 58 63 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. About one-half of the viruses with K65R did not have M184V, making K65R the second largest contributor to the cumulative proportion of viruses with a major NRTI DRM. 2015 PloS one Result HIV K65R;K65R;M184V 35;67;53 39;71;58 NRTI 156 160 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Fig 2 shows that in viruses from individuals in LMICs with intermediate or high-level NRTI resistance following VF on a first-line NRTI/NNRTI-containing regimen, the most common major DRMs were M184V (91.5%) and M184I (3.7%), K65R (9.8%), and the TAMs K70R (14.6%), T215Y (11.0%) and T215F (9.3%). 2015 PloS one Result HIV K65R;K70R;M184I;M184V;T215F;T215Y;K65R;K70R;M184I;M184V;T215F;T215Y 227;253;213;195;285;267;226;252;212;194;284;266 231;257;218;200;290;272;230;256;217;199;289;271 NNRTI;NRTI;NRTI 136;86;131 141;90;135 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Fig 2 shows that the most common NNRTI DRMs in viruses from individuals in LMICs with intermediate or high-level resistance on a first-line NRTI/NNRTI-containing regimen were K103N (45.5%), Y181C (27.0%), G190A (21.0%), and V106M (18.7%). 2015 PloS one Result HIV G190A;K103N;V106M;Y181C;G190A;K103N;V106M;Y181C 206;176;225;191;205;175;224;190 211;181;230;196;210;180;229;195 NNRTI;NNRTI;NRTI 33;145;140 38;150;144 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. In fact, I50L is associated with increased susceptibility to LPV, DRV and other PIs. 2015 PloS one Result HIV I50L 9 13 PI 80 83 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Indeed, among both adults and children receiving ABC, L74V/I were the second most common major NRTI DRMs associated with acquired NRTI resistance after M184V. 2015 PloS one Result HIV L74I;L74V;M184V 54;54;152 60;60;157 NRTI;NRTI 95;130 99;134 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. K103N, Y181C and G190A were the three most common NNRTI DRMs in all regions and subtypes, occurring in more than 60% of viruses with intermediate or high-level NNRTI TDR. 2015 PloS one Result HIV G190A;Y181C;K103N 17;7;0 22;12;5 NNRTI;NNRTI 50;160 55;165 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. K103S, V106M, Y188L and G190S/E accounted for most of the remaining transmitted major NNRTI DRMs in LMICs. 2015 PloS one Result HIV G190E;G190S;V106M;Y188L;K103S 24;24;7;14;0 31;31;12;19;5 NNRTI 86 91 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. K65R also occurred in 48% of 467 individuals with VF on a first-line TDF-containing regimen (S5 Table). 2015 PloS one Result HIV K65R 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. K70R, L74V/I, Y115F, M184I, and T215Y/F were the most common major non-tier 1 DRMs associated with ADR on a first-line NRTI/NNRTI-containing regimen and with TDR. 2015 PloS one Result HIV L74I;L74V;M184I;T215F;T215Y;Y115F;K70R 6;6;21;32;32;14;0 12;12;26;39;39;19;4 NNRTI;NRTI 124;119 129;123 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. L74V/I rarely occurred in the absence of M184V. 2015 PloS one Result HIV L74I;L74V;M184V 0;0;41 6;6;46 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. M184I, K65R, L74V/I, Y115F and the TAMs K70R and T215Y/F were the next most common transmitted major NRTI DRMs. 2015 PloS one Result HIV K65R;K70R;L74I;L74V;T215F;T215Y;Y115F;M184I 7;40;13;13;49;49;21;0 11;44;19;19;56;56;26;5 NRTI 101 105 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. M184V was the most common transmitted major NRTI-associated DRM, occurring in 54% of viruses from individuals with intermediate or high-level NRTI TDR in LMICs and 31% of viruses from individuals with intermediate or high-level NRTI TDR in upper-income countries. 2015 PloS one Result HIV M184V 0 5 NRTI;NRTI;NRTI 44;142;228 48;146;232 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Of the six DRMs with the highest cumulative sensitivity for detecting intermediate or high-level resistance to an NRTI or NNRTI on a first-line NRTI/NNRTI-containing regimen (K65R, M184V, K103N, V106M, Y181C, G190A), all but K65R and V106M were also the most common DRMs occurring in individuals with TDR. 2015 PloS one Result HIV G190A;K103N;K65R;K65R;M184V;V106M;V106M;Y181C 209;188;175;225;181;195;234;202 214;193;179;229;186;200;239;207 NNRTI;NNRTI;NRTI;NRTI 122;149;114;144 127;154;118;148 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Published reports of aggregated data indicate that I50L and N88S are the main DRMs developing in PI-naive individuals with VF on an ATV- or ATV/r-containing regimen. 2015 PloS one Result HIV I50L;N88S 51;60 55;64 PI 97 99 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. The most common major PI DRMs were V82A, I76V, I84V and L47A. 2015 PloS one Result HIV I76V;I84V;L47A;V82A 41;47;56;35 45;51;60;39 PI 22 24 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. The next two most common major LPV DRMs:I50V and V82F -accounted for an additional 4% of viruses with predicted intermediate or high-level LPV resistance. 2015 PloS one Result HIV I50V;V82F 40;49 44;53 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. The remaining 8% of viruses with predicted intermediate or high-level LPV resistance had a combination of two or more PI DRMs with lower mutation scores, including V32I, M46I, I54M/L/V, I47V, V82S/T/M and L90M. 2015 PloS one Result HIV I47V;I54L;I54M;I54V;L90M;M46I;V32I;V82M;V82S;V82T 186;176;176;176;205;170;164;192;192;192 190;184;184;184;209;174;168;200;200;200 PI 118 120 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. The spectrum of DRMs in 712 children was similar to adults with the exception that L74V/I occurred more often in children because a higher proportion of children received an ABC-containing regimen (S6 and S7 Tables). 2015 PloS one Result HIV L74I;L74V 83;83 89;89 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. The TAMs M41L, D67N/E/G and K219Q/E/N/R and the T215 revertant mutations (T215C/D/E/S/I/V) were the most common non-major transmitted NRTI DRMs. 2015 PloS one Result HIV D67E;D67G;D67N;K219E;K219N;K219Q;K219R;M41L;T215C;T215D;T215E;T215I;T215S;T215V 15;15;15;28;28;28;28;9;74;74;74;74;74;74 23;23;23;39;39;39;39;13;89;89;89;89;89;89 NRTI 134 138 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. The TAMs nearly always occurred in combination with M184V and contributed less to the cumulative proportion of viruses with a major NRTI DRM than did K65R. 2015 PloS one Result HIV K65R;M184V 150;52 154;57 NRTI 132 136 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. The two next most common NNRTI DRMs:Y188L and G190S -accounted for an additional 5.7% of viruses with acquired intermediate or high-level NNRTI resistance. 2015 PloS one Result HIV G190S;Y188L 46;36 51;41 NNRTI;NNRTI 25;138 30;143 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V106M was significantly more common in subtype C viruses and was the fourth most common NNRTI DRM in this subtype. 2015 PloS one Result HIV V106M 0 5 NNRTI 88 93 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V106M was the second-most common NNRTI DRM in subtype C viruses, occurring in 33% of individuals with a major NNRTI DRM. 2015 PloS one Result HIV V106M 0 5 NNRTI;NNRTI 33;110 38;115 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Y188L and G190S were the most common major non-tier 1 NNRTI DRMs associated with ADR on a first-line NRTI/NNRTI-containing regimen and among the most common non-tier 1 NNRTI DRMs associated with TDR. 2015 PloS one Result HIV G190S;Y188L 10;0 15;5 NNRTI;NNRTI;NNRTI;NRTI 54;106;168;101 59;111;173;105 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. (Figure 2b); These findings illustrate a potential CNS-specific fitness cost of the K165R SIV Gag escape mutation with reduced CNS replication without altering SIV replication in the periphery. 2016 Journal of neurovirology Result HIV K165R 84 89 Gag 94 97 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Although the viral growth curve of SIV/17E-Fr K165R was more similar to wildtype SIV/17E-Fr in infected primary microglia than in primary lymphocytes or macrophages, escape virus still demonstrated lower peak virus and a lower growth curve (Figure 1d), although this difference was only significant at d4 post infection. 2016 Journal of neurovirology Result HIV K165R 46 51 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. As expected, plasma genotyping of SIV gag in the three animals inoculated with SIV/17E-Fr K165R showed SIV Gag K165R stability up to day 28 post inoculation (Figure 4a,b,c); however, CSF genotyping showed reversion to wildtype Gag KP9 starting as early as 7 days post inoculation in two of three animals (Figure 3d,e,f). 2016 Journal of neurovirology Result HIV K165R;K165R 90;111 95;116 Gag;Gag;Gag 38;107;227 41;110;230 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. As expected, SIV/17E-Fr K165R was also replication competent in primary lymphocytes and macrophages, but similar to the findings in CEMx174 cells, had lower growth curves compared to the parental virus containing wildtype Gag KP9 (Figure 1b,c). 2016 Journal of neurovirology Result HIV K165R 24 29 Gag 222 225 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. As expected, vaccinated animals developed the Gag K165R viral escape mutation rapidly in the plasma (Figure 6a,b) and developed more complete and sustained plasma viral escape mutations compared to the SIV/17E-Fr-inoculated, unvaccinated control animals (Figure 3a,b,c). 2016 Journal of neurovirology Result HIV K165R 50 55 Gag 46 49 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. By infecting the HIV/SIV permissive hybrid B/T cell line CEMx174, we showed that the molecular clone SIV/17E-Fr K165R was able to replicate successfully, but produced less virus compared to wildtype SIV/17E-Fr (Figure 1a). 2016 Journal of neurovirology Result HIV K165R 112 117 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Consistent with previous findings from our group, we detected emergence of the escape mutation Gag K165R in plasma of all three Mane-A1*084:01 pigtailed macaques that were inoculated with wildtype SIV/17E-Fr (Figure 3a,b,c) although we failed to see escape mutations develop in the CSF of these animals (Figure 3d,e,f). 2016 Journal of neurovirology Result HIV K165R 99 104 Gag 95 98 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. In addition, we sequenced SIV gag in both the peripheral (plasma) and CNS (CSF) compartments in animals inoculated with SIV/17E-Fr K165R (Figure 4) to track reversion from escape Gag K165R to wildtype Gag KP9 in vivo. 2016 Journal of neurovirology Result HIV K165R;K165R 131;183 136;188 Gag;Gag;Gag 30;179;201 33;182;204 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. In contrast, the CSF viral load of animals inoculated with SIV/17E-Fr/K165R was lower than two of three macaques inoculated with SIV/17E-Fr after acute infection at d49 p.i. 2016 Journal of neurovirology Result HIV K165R 70 75 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Interestingly, terminal SIV Gag sequencing showed 65% wildtype Gag KP9 (52/80 clones) and only 35% escape mutant Gag K165R (28/80 clones), suggesting that wildtype virus outcompeted SIV/17E-Fr K165R. 2016 Journal of neurovirology Result HIV K165R;K165R 117;193 122;198 Gag;Gag;Gag 28;63;113 31;66;116 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Interestingly, the Gag K165R escape mutation developed more rapidly in the CSF of vaccinated animals compared to the periphery (Figure 6c,d), while CSF mutations did not develop in any of the SIV/17E-Fr- inoculated, unvaccinated animals (Figure 3d,e,f). 2016 Journal of neurovirology Result HIV K165R 23 28 Gag 19 22 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Longitudinal plasma viral loads in animals inoculated with mutant SIV/17E-Fr K165R were nearly identical to those animals inoculated with wildtype SIV/17E-Fr (Figure 2a). 2016 Journal of neurovirology Result HIV K165R 77 82 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Previous studies that challenged Mane-A1*084:01-positive pigtailed macaques with a natural SIV isolate containing the Gag K165R mutation showed maintenance of the escape mutation. 2016 Journal of neurovirology Result HIV K165R 122 127 Gag 118 121 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Previous studies using SHIV strains have shown rapid reversion of the Gag K165R mutation to wildtype KP9 when inoculated into animals that do not mount an immunologic response against the KP9 epitope, suggesting that the K165R mutation incurs a dramatic fitness cost. 2016 Journal of neurovirology Result HIV K165R;K165R 74;221 79;226 Gag 70 73 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Reduced in vitro viral replication regardless of cell type is consistent with the premise that the Gag K165R mutation incurs a general fitness cost. 2016 Journal of neurovirology Result HIV K165R 103 108 Gag 99 102 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Replication of wildtype SIV/17E-Fr and escape SIV/17E-Fr K165R were directly compared in vitro in the lymphocyte cell line CEMx174, macaque peripheral blood lymphocytes, macrophages, and microglia (Figure 1). 2016 Journal of neurovirology Result HIV K165R 57 62 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. Reversion to wildtype Gag KP9 in cells infected with escape mutant SIV/17E-Fr K165R occurred at a very low rate (0.5%, or 1/81 clones, terminally). 2016 Journal of neurovirology Result HIV K165R 78 83 Gag 22 25 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. The goals of these in vitro studies were to 1) confirm that the escape mutation-bearing virus construct SIV/17E-Fr K165R was replication competent in vitro, and 2) compare the replication kinetics of SIV/17E-Fr K165R versus the wildtype clone SIV/17E-Fr at the cellular level. 2016 Journal of neurovirology Result HIV K165R;K165R 115;211 120;216 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. To determine whether fitness cost of the Gag K165R mutation demonstrated in vitro was recapitulated in vivo, we inoculated three Mane-A1*084:01-positive pigtailed macaques with SIV/17E-Fr K165R (table 1, group 2) and compared SIV replication with three Mane-A1*084:01-positive pigtailed macaques inoculated with wildtype SIV/17E-Fr (table 1, group 1). 2016 Journal of neurovirology Result HIV K165R;K165R 45;188 50;193 Gag 41 44 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. To induce KP9-specific CTL responses that specifically target the SIV Gag KP9 epitope and thereby accelerate K165R escape in animals inoculated with SIV/17E-Fr, we utilized a unique vaccine platform designed to induce a robust CTL response using a virus-like particle that solely presented the SIV Gag KP9 peptide. 2016 Journal of neurovirology Result HIV K165R 109 114 Gag;Gag 70;298 73;301 26727909 Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. When CEMx174 cells were infected with 50:50 wildtype SIV/17E-Fr and mutant SIV/17E-Fr K165R, viral growth kinetics were intermediate, as would be expected (data not shown). 2016 Journal of neurovirology Result HIV K165R 86 91 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. As reported previously, only 5 of the 9 cases of resistance had both evidence of PrEP use (detectable levels of tenofovir) and resistance to the PrEP drugs they were taking (FTC selects for K65R and M184IV; TDF selects for K65R and K70E), suggesting that the resistance mutations detected in these 5 seroconverters were likely due to PrEP selection. 2016 AIDS (London, England) Result HIV K65R;K65R;K70E;M184I;M184V 190;223;232;199;199 194;227;236;205;205 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. Case 2-283 had M184V in 16% of virus variants when seroconversion was detected and 1.7% M184V 1 month later, which faded below 1% by 6 months and remained undetectable through 24 months. 2016 AIDS (London, England) Result HIV M184V;M184V 15;88 20;93 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. Case 2-299, who also had 1.2% K65R, was lost to follow-up after seroconversion. 2016 AIDS (London, England) Result HIV K65R 30 34 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. M184I, which is naturally polymorphic and known to occur without drug exposure, fluctuated at low levels between below detection and 6% throughout follow-up (Figure 2). 2016 AIDS (London, England) Result HIV M184I 0 5 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. The 3 other cases of resistance (1 TDF: 2-326; 2 placebo: 6-283 and 2-316) had only low levels of M184I at seroconversion ranging from 1-2.5%. 2016 AIDS (London, England) Result HIV M184I 98 103 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. The other 4 cases of PrEP-selected resistance were individuals randomized to FTC/TDF (2 individuals with unrecognized acute infection at randomization: 3-269 and 2-331; and 2 individuals who acquired HIV post-randomization: 2-299 and 4-321) who had M184V or M184IV at levels ranging from 1% to 99% at detection of seroconversion. 2016 AIDS (London, England) Result HIV M184I;M184V;M184V 258;258;249 264;264;254 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. The remaining 4 cases of resistance were individuals who did not have detectable levels of PrEP drug in any of their HIV RNA or antibody-positive plasma samples (2-283, 6-283, 2-316, the latter two were assigned to the placebo arm), or whose resistance mutation was not associated with their assigned PrEP regimen (2-326 had M184I, which causes resistance to FTC, but this individual was assigned to TDF-alone as PrEP). 2016 AIDS (London, England) Result HIV M184I 325 330 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. This included 1 individual (3-225) randomized to TDF during unrecognized acute infection who had K65R and K70E detected in 56% and 10% of virus variants, respectively, when seroconversion was first detected. 2016 AIDS (London, England) Result HIV K65R;K70E 97;106 101;110 26731753 Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. This individual had no evidence of PrEP drug at clinic visits either before or after seroconversion, and the M184V mutation may have been a result of transmitted resistance. 2016 AIDS (London, England) Result HIV M184V 109 114 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. Clinical specimens (N = 26) from Kenyan's infected with HIV-1 subtypes A, C, D, AE and G, and plasmid standards at 0, 5 and 50% MUT were tested for drug resistance mutations at four HIV codons (K103N, Y181C, M184V and G190A, N total = 104) by both paper CDD and plate CDD OLA (Figs 4 and 5). 2016 PloS one Result HIV G190A;K103N;M184V;Y181C 218;194;208;201 223;199;213;206 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. To investigate the analytical response of OLA using the paper CDD, a plasmid mixture dilution series for the Y181C mutation (0, 2, 5, 10, 25, 50, 75, 100% MUT) was tested for MUT and WT responses and compared to the signals obtained with the plate CDD (Fig 3). 2016 PloS one Result HIV Y181C 109 114 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Furthermore, we tested RMNC6 against several mutants conferring resistance to NNRTIs such as K103N, Y181C and Y188L, and against the HIV-1 group O RT which shows natural resistance to NNRTIs due to the presence of the amino acid substitutions A98G, V179E and Y181C (S2 Appendix). 2016 PloS one Result HIV A98G;K103N;V179E;Y181C;Y181C;Y188L 243;93;249;100;259;110 247;98;254;105;264;115 NNRTI;NNRTI;RT 78;184;147 84;190;149 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. In contrast, HIV-1 group O RT and mutants K103N and Y188L showed decreased susceptibility to EFV (7.7- to 9.2-fold increases in the IC50 values relative to the wild type HIV-1 group M subtype B RT) (Table 1). 2016 PloS one Result HIV K103N;Y188L 42;52 47;57 RT;RT 27;194 29;196 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Interestingly, BTP showed a different profile and was an efficient inhibitor of all mutants except N474A that had an IC50 value 4.5 times higher than the one obtained with the wt RT. 2016 PloS one Result HIV N474A 99 104 RT 179 181 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Interestingly, the E224A RT showed a 6-fold reduced susceptibility to RMNC6 in RNase H assays, while mutant enzymes such as V108A and V106A showed IC50 values 4 and 10 times higher, respectively, in comparison with the wt RT. 2016 PloS one Result HIV E224A;V106A;V108A 19;134;124 24;139;129 RT;RT 25;222 27;224 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Mutants V108A and V106A were also obtained since Val108 and Val106 were identified as potentially important for inhibitor binding. 2016 PloS one Result HIV V106A;V108A 18;8 23;13 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Results showed a consistent reduction in the kcat values with respect to wt RT for all mutant RTs, and a slight reduction in template-primer Km values for A508V, V106A, V108A and E224A RTs, resulting in a reduced efficiency (kcat/Km) for V108A, E224A and A502F RTs (2-, 3 and 12-fold, respectively) (Table 5). 2016 PloS one Result HIV A502F;A508V;E224A;E224A;V106A;V108A;V108A 255;155;179;245;162;169;238 260;160;184;250;167;174;243 RT;RT;RT;RT 76;94;185;261 78;97;188;264 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. The 6.5 folds reduction in RMNC6 susceptibility obtained with HIV-1 group O RT in RNase H activity assays (Table 1) is consistent with the effects observed with single-mutants A502F or A508V (Table 4), since amino acid substitutions found in the HIV-1 group O RT would also contribute to reducing the size of the putative RMNC6 binding pocket in the RNase H domain. 2016 PloS one Result HIV A502F;A508V 176;185 181;190 RT;RT 76;260 78;262 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. The RNase H function of mutant RTs A502F and A508V showed 4- to 10-fold reduced susceptibility to RMNC6 in RNase H assays, while individual mutations of N474A and Y501A caused full resistance to the isatin derivative. 2016 PloS one Result HIV A502F;A508V;N474A;Y501A 35;45;153;163 40;50;158;168 RT 31 34 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Therefore, we tested whether mutant A502F and A508V RTs had altered RNase H kinetics cleavage efficiency. 2016 PloS one Result HIV A502F;A508V 36;46 41;51 RT 52 55 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. To investigate possible RMNC6 binding into this pocket, we mutated residues Ala502 to Phe and Ala508 to Val in an attempt to reduce the space available for RMNC6 accommodation. 2016 PloS one Result HIV A502F;A508V 76;94 89;107 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. When the RDDP function of mutant RTs was assayed, a similar pattern emerged, even though the extent of the reduction in the IC50 values was lower (1.4, 3.3 and 2.5 muM for E224A, V106A and V108A RTs, respectively). 2016 PloS one Result HIV E224A;V106A;V108A 172;179;189 177;184;194 RT;RT 33;195 36;198 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. With respect to RMNC6 binding to pocket 1, the observed partial loss in potency of RNase H inhibition observed for V106A, V108A and E224A RTs (Table 3) supported two different hypotheses. 2016 PloS one Result HIV E224A;V106A;V108A 132;115;122 137;120;127 RT 138 141 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. By multiple stepwise logistic regression, having M184V/I (OR 0.11; 95% CI 0.02-0.62, p = 0.013), condom use (OR 2.38; 95% CI 1.12-5.06, p = 0.024), and adherence per 5% increase (OR 1.16; 95% CI 1.00-1.35, p = 0.044) were associated with HIV RNA <50 copies/mL after 6 months of ART. 2016 PloS one Result HIV M184I;M184V 49;49 56;56 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. By univariate logistic regression, CD4 cell count <200 cells/mm3 at ART initiation (OR 2.03; 95% CI 1.01-4.09, p = 0.047), adherence per 5% increase (OR 1.22; 95% CI 1.07-1.39, p = 0.004), having primary HIVDR (OR 0.31; 95% CI 0.10-0.97, p = 0.043), having M184V/I (OR 0.08; 95% CI 0.02-0.44, p = 0.003), having G190S/A (OR 0.09; 95% CI 0.01-0.90, p = 0.040), and having Y181C/I (OR 0.07; 95% CI 0.01-0.61, p = 0.017) were significantly associated with HIV RNA <50 copies/mL after 6 months of ART (Table 3). 2016 PloS one Result HIV G190A;G190S;M184I;M184V;Y181C;Y181I 312;312;257;257;371;371 319;319;264;264;378;378 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. No patients had the mutations Y188C/L/H and Q151M. 2016 PloS one Result HIV Q151M;Y188C;Y188H;Y188L 44;30;30;30 49;39;39;39 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. The prevalence of each mutation was: K103N (6.0%), M184V (3.0%), G190A (2.3%), Y181C (2.3%), M184I (1.5%), V106I (1.1%), Y181I (0.7%), V108I (0.4%), and Y181V (0.4%). 2016 PloS one Result HIV G190A;K103N;M184I;M184V;V106I;V108I;Y181C;Y181I;Y181V 65;37;93;51;107;135;79;121;153 70;42;98;56;112;140;84;126;158 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Furthermore, the M184V/I mutation was less common than NNRTI resistance across all regions except in eastern Africa. 2016 The Lancet. Infectious diseases Result HIV M184I;M184V 17;17 24;24 NNRTI 55 60 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Prevalence of cytosine analogue resistance (M184V/I) was highest in sub-Saharan Africa and Latin America and lowest in western Europe. 2016 The Lancet. Infectious diseases Result HIV M184I;M184V 44;44 51;51 26831472 Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. These results did not change when analysis was restricted to individuals who had evidence of the K65R mutation, either with or without M184V/I (appendix). 2016 The Lancet. Infectious diseases Result HIV K65R;M184I;M184V 97;135;135 101;142;142 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. A second variant was constructed which in addition harbors the reversal R65K (MR-65K-70R), to abrogate negative effects of K65R on AZT excision. 2016 Nucleic acids research Result HIV K65R;R65K 123;72 127;76 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. A400T has been associated with increased AZTMP excision in subtypes B and CRF01_AE. 2016 Nucleic acids research Result HIV A400T 0 5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. A62V and S68G restore the impaired nucleotide incorporation of the K65R mutation, thus improving the replication capacity of the virus. 2016 Nucleic acids research Result HIV K65R;S68G;A62V 67;9;0 71;13;4 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. According to the HIV Drug Resistance Database (http://hivdb.stanford.edu/), K101Q, E138Q and exchanges at position V179 are also detected in patients treated with EFV. 2016 Nucleic acids research Result HIV E138Q;K101Q 83;76 88;81 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Although analyses with subtype B RT indicated that K65R and the TAM T215F/Y are not compatible. 2016 Nucleic acids research Result HIV K65R;T215F;T215Y 51;68;68 55;75;75 RT 33 35 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Although G190E is a NNRTI resistance mutation, it is often detected with V75I of the Q151M complex. 2016 Nucleic acids research Result HIV G190E;Q151M;V75I 9;85;73 14;90;77 NNRTI 20 25 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Although the patient received only RT inhibitors targeted against the polymerase domain, compared to the subtype CRF02_AG WT 11 amino acid substitutions were detected in the connection subdomain (A322T, G324E, D335G, V380I, A400T, M403T) and in the RNase H domain (I469L, T470P, K512R, L520Q, K530R, S554N, V556I) (Figure 1). 2016 Nucleic acids research Result HIV A322T;A400T;D335G;G324E;I469L;K512R;K530R;L520Q;M403T;S554N;T470P;V380I;V556I 196;224;210;203;265;279;293;286;231;300;272;217;307 201;229;215;208;270;284;298;291;236;305;277;222;312 Pol;RT 70;35 80;37 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. AZT resistant HIV-1 strains typically possess TAMs to remove incorporated NRTIs as AZTMP or d4T, whereas the Q151M discrimination pathway usually occurs upon administration of other NRTIs like 3TC and ddI. 2016 Nucleic acids research Result HIV Q151M 109 114 NRTI;NRTI 74;182 79;187 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. E312Q, G335C/D, N348I, A360I/V, V365I and A376S) have been identified that significantly contribute to AZT resistance by reducing RNase H activity. 2016 Nucleic acids research Result HIV A360I;A360V;A376S;G335C;G335D;N348I;V365I;E312Q 23;23;42;7;7;16;32;0 30;30;47;14;14;21;37;5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Finally, in July 2008 four out of six TAMs relevant for highly efficient AZTMP excision (M41L, D67N, T215Y and K219E, missing K70R and L210W) as well as four out of five discrimination mutations (A62V, V75I, F116Y and Q151M, lacking F77I) were present. 2016 Nucleic acids research Result HIV A62V;D67N;F116Y;F77I;K219E;K70R;L210W;M41L;Q151M;T215Y;V75I 196;95;208;233;111;126;135;89;218;101;202 200;99;213;237;116;130;140;93;223;106;206 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. First, the K70R mutation, which is the missing fifth TAM residue promoting excision, was introduced (MR-70R). 2016 Nucleic acids research Result HIV K70R 11 15 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Furthermore, R172K might contribute to the observed lower DNA binding affinities of the MR-RT variants. 2016 Nucleic acids research Result HIV R172K 13 18 RT 91 93 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Furthermore, the accessory discrimination mutations A62V and V75I emerged, but F77I has never been found (Supplementary Table S1). 2016 Nucleic acids research Result HIV A62V;F77I;V75I 52;79;61 56;83;65 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. G190E confers a more than 50-fold reduced sensitivity toward EFV but results in low polymerization activity. 2016 Nucleic acids research Result HIV G190E 0 5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. G190E severly impairs polymerization activities due to repositioning of the primer, which in turn is antagonistic to excision. 2016 Nucleic acids research Result HIV G190E 0 5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. G196E is also detected in NRTI resistant viruses. 2016 Nucleic acids research Result HIV G196E 0 5 NRTI 26 30 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. However, in subtype B the MR-RT exchange V179 to Gly (V179G) has not been found (http://hivdb.stanford.edu/). 2016 Nucleic acids research Result HIV V179G 54 59 RT 29 31 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. However, it was not sufficient for AZTMP excision to occur even if all five TAMs were present (MR-70R), or if in addition K65R (MR-65K-70R) or Q151M (MR-70R-151Q) were reversed (Figure 4). 2016 Nucleic acids research Result HIV K65R;Q151M 122;143 126;148 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. However, L210W has not been identified frequently in the CRF02_AG subtype. 2016 Nucleic acids research Result HIV L210W 9 14 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. However, the A400T mutation as well as two of the mutations existing in the RNase H domain (K512R, K530R) have been shown to occur in subtype B during NRTI treatment (Figure 1) (see below). 2016 Nucleic acids research Result HIV A400T;K512R;K530R 13;92;99 18;97;104 NRTI 151 155 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In a third variant, the pivotal discrimination substitution Q151M was reversed to WT and combined with K70R (MR-RT-70R-151M) to further support the excision reaction. 2016 Nucleic acids research Result HIV K70R;Q151M 103;60 107;65 RT 112 114 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In addition, the enzyme also carries the codon K65R which was suggested to antagonize AZT excision. 2016 Nucleic acids research Result HIV K65R 47 51 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In HIV-1 subtype B two of the mutations, A400T and K512R, have been correlated with the occurrence of TAMs in a dose-dependent manner, being more frequent as the number of TAMs increased. 2016 Nucleic acids research Result HIV A400T;K512R 41;51 46;56 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In HIV-1 subtype B, strains harboring K65R together with multiple TAMs were only detected with a frequency of <0.1%. 2016 Nucleic acids research Result HIV K65R 38 42 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In May 2003 the accessory TAM K219E occurred (Supplementary Table S1) although at that point in time the two NRTIs 3TC and TDF, which are not readily excised, were used (Supplementary Table S2). 2016 Nucleic acids research Result HIV K219E 30 35 NRTI 109 114 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. In MR-RT only K277R was found in combination with P272A, while at position 286 a Gly is present in WT and MR-RT (Figure 1). 2016 Nucleic acids research Result HIV K277R;P272A 14;50 19;55 RT;RT 6;109 8;111 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Interestingly, probably due to the presence of the resistance mutation K65R, MR-70R-151Q was neither able of efficient AZTTP discrimination nor AZTMP excision. 2016 Nucleic acids research Result HIV K65R 71 75 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. K65R confers resistance to d4T, TDF and possibly to 3TC, ddI and ABC, but not to AZT. 2016 Nucleic acids research Result HIV K65R 0 4 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Obviously, the Q151M pathway developed due to the administration of drugs that could not be efficiently eliminated by the excision pathway. 2016 Nucleic acids research Result HIV Q151M 15 20 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Only the combination of both reversals of K65R and Q151M in the presence of all TAMs (MR-65K-70R-151Q) resulted in AZTMP excision (Figure 4), albeit less efficient than with AZTres-B RT. 2016 Nucleic acids research Result HIV K65R;Q151M 42;51 46;56 RT 183 185 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Only when the reversal M151Q of the major discrimination codon was present (MR-70R-151Q, MR65K-70R-151Q, AZTres-B), discrimination between TTP and AZTTP was strongly impaired. 2016 Nucleic acids research Result HIV M151Q 23 28 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Our data indicate that the two pathways are mutually exclusive and that although four TAMs including T215Y are present, only AZTTP discrimination by the Q151M complex is functional, thus enabling the enzyme to exhibit high level resistance against various NRTIs that have been administered during therapy. 2016 Nucleic acids research Result HIV Q151M;T215Y 153;101 158;106 NRTI 256 261 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Overall, MR-RT revealed a kinetic efficiency (kcat/KM) comparable to WT RT, while the insertion of the K70R codon resulted in a significantly lower RNase H enzyme efficiency (Table 3). 2016 Nucleic acids research Result HIV K70R 103 107 RT;RT 12;72 14;74 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. R172K was shown to decrease DNA binding affinity and to suppress the excision mechanism by TAMs. 2016 Nucleic acids research Result HIV R172K 0 5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. S68G which has been shown to improve the replicative capacity (Figure 1). 2016 Nucleic acids research Result HIV S68G 0 4 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Sequence comparisons of HIV-1 positive naive and HAART treated patients revealed a correlation between K20R and 3TC resistance and an association with TAMs, while T39A appears to be associated with previous AZT and d4T treatment and with the development of TAMs. 2016 Nucleic acids research Result HIV K20R;T39A 103;163 107;167 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Sequencing of the patient isolate in March 2000 revealed the presence of four TAMs (M41L, D67N, K70R, T215Y) as well as two mutations of the Q151M discrimination pathway (F116Y and Q151M), whereas the K65R mutation was still missing (Supplementary Table S1). 2016 Nucleic acids research Result HIV D67N;F116Y;K65R;K70R;M41L;Q151M;Q151M;T215Y 90;171;201;96;84;141;181;102 94;177;205;100;88;146;186;107 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Similarly, the V75I exchange is compensatory for G190E, which emerges upon NNRTI treatment. 2016 Nucleic acids research Result HIV G190E;V75I 49;15 54;19 NNRTI 75 80 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. T215Y and Q151M, in addition to K65R raised the question as to which pathway could still be used by MR-RT. 2016 Nucleic acids research Result HIV K65R;Q151M;T215Y 32;10;0 36;15;5 RT 103 105 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. TAM L210W, which in subtype B occurs occasionally in combination with other TAMs, depending on the NRTIs used, could never be detected. 2016 Nucleic acids research Result HIV L210W 4 9 NRTI 99 104 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. TAMs and the Q151M complex, can be directly attributed to resistance mutations. 2016 Nucleic acids research Result HIV Q151M 13 18 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The accessory substitutions of the Q151M MDR complex help retain the replication capacity or improve the discrimination efficiency. 2016 Nucleic acids research Result HIV Q151M 35 40 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The frequency of K530R is also increased in NRTI treated persons (12.1% versus 1.1% in untreated isolates). 2016 Nucleic acids research Result HIV K530R 17 22 NRTI 44 48 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The KM for AZTTP of MR-RT compared with the two variants comprising the reverse codon M151Q. 2016 Nucleic acids research Result HIV M151Q 86 91 RT 23 25 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The P236L mutation characteristic for delavirdine (DLV) resistance is absent in MR-RT (http://hivdb.stanford.edu/). 2016 Nucleic acids research Result HIV P236L 4 9 RT 83 85 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The polymorphism R172K impairs AZTMP excision, while T165I is associated with Q151M. 2016 Nucleic acids research Result HIV Q151M;R172K;T165I 78;17;53 83;22;58 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. the polymorphism R172K or the exchange G190E, which are both present in MR-RT but not in the WT. 2016 Nucleic acids research Result HIV G190E;R172K 39;17 44;22 RT 75 77 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The polymorphisms R211K and L214F contribute to AZT resistance, however, in MR-RT the reversal F214L was detected. 2016 Nucleic acids research Result HIV F214L;L214F;R211K 95;28;18 100;33;23 RT 79 81 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. The presence of K65R in combination with multiple TAMs is particularly interesting. 2016 Nucleic acids research Result HIV K65R 16 20 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. This might be the reason for the selection of the discrimination substitutions since according to the HIV Drug Resistance Database (http://hivdb.stanford.edu/) Q151M and the Q151M complex support low to moderate resistance to 3TC and efficient discrimination of various other NRTIs which have also been used during ongoing therapy (Supplementary Table S2). 2016 Nucleic acids research Result HIV Q151M;Q151M 158;174 165;179 NRTI 276 281 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. V118I occurs in combination with multiple TAMs. 2016 Nucleic acids research Result HIV V118I 0 5 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. What is more, K65R has never been found in combination with T215F/Y, indicating that, in contrast to subtype AG, in subtype B K65R and the T215F/Y pathway are not compatible. 2016 Nucleic acids research Result HIV K65R;K65R;T215F;T215F;T215Y;T215Y 14;126;60;139;60;139 18;130;67;146;67;146 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. While the K70R mutation was never discovered in later genotypic analyses, K65R was first detected in June 2002. 2016 Nucleic acids research Result HIV K65R;K70R 74;10 78;14 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. Each rFS5929R1 virus without I47V (rFS5929R1I47) and rFS5929R1 without I50V (rFS5929R1I50) exhibited a >175-fold and 96.9-fold increase in DRV resistance, respectively, whereas the rFS5929R1 without the two mutations (rFS5929R1I47/I50) exhibited a 20.4-fold increase. 2016 Frontiers in microbiology Result HIV I47V;I50V 29;71 33;75 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. FS5929 contained one minor DRV resistance mutation (L33F) (Table 2) and conferred the highest DRV resistance (7.7-fold increase compared with the WT HIV-1 JR-CSF) of the 20 multiple drug-resistant samples selected for this study (Figure 1 and Table 1). 2016 Frontiers in microbiology Result HIV L33F 52 56 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. Interestingly, the regions included the two major DRV resistance mutations (I47V and I50V) and one minor mutation (V32I), which were induced by the in vitro selection (Figure 3C). 2016 Frontiers in microbiology Result HIV I47V;I50V;V32I 76;85;115 81;89;119 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. The major virus (referred to as FS5929R1) had two major DRV resistance mutations (I47V and I50V), four minor mutations (V11I, V32I, L33F, and L89V), and V82F. 2016 Frontiers in microbiology Result HIV I47V;I50V;L33F;L89V;V11I;V32I;V82F 82;91;132;142;120;126;153 87;95;136;146;124;130;157 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. The other minor variants had I47V mutation and either of I50V or L76V mutation although the other sequences were similar to that of the major virus. 2016 Frontiers in microbiology Result HIV I47V;I50V;L76V 29;57;65 33;61;69 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. The results suggest that the two major mutations, especially I50V, largely contribute to the DRV resistance in rFS5929R1. 2016 Frontiers in microbiology Result HIV I50V 61 65 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. We also constructed three recombinant rFS5929R1 viruses lacking the major DRV resistance mutations I47V and/or I50V to assess the contribution of the major mutations to DRV resistance. 2016 Frontiers in microbiology Result HIV I47V;I50V 99;111 103;115 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. Although the virus harboring the K101Q\H221Y mutation was found to be hyper-susceptible to EFV, the slope of the curve was significantly decreased. 2016 PloS one Result HIV H221Y;K101Q 39;33 44;38 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. As shown in Fig 3C, the triple-mutant G48V\I54V\V82A affected both IC50 and slope for this agent, whereas M46I\N88S reduced the IC50 but not the slope. 2016 PloS one Result HIV G48V;I54V;M46I;N88S;V82A 38;43;106;111;48 42;47;110;115;52 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. For example, the inhibition curve of the K103N\H221Y\T215Y mutation was shifted toward a higher drug concentration for EFV (12.09-fold), with no alterations in shape. 2016 PloS one Result HIV H221Y;K103N;T215Y 47;41;53 52;46;58 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. Furthermore, Fig 3D showed that the G48V\I54V mutation increased the IC50 without affecting slope of dose-response curve for SQV. 2016 PloS one Result HIV G48V;I54V 36;41 40;45 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. G48V\I54V\V82A mutations increased the IC50 and reduced the slope for RTV, leading to a marked decrease in RTV susceptibility at concentrations above the IC50. 2016 PloS one Result HIV I54V;V82A;G48V 5;10;0 9;14;4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. However, the K103N\H221Y\Y181C\T215Y mutation led to an intermediate shift in IC50 but a marked reduction in slope (Fig 3B). 2016 PloS one Result HIV H221Y;K103N;T215Y;Y181C 19;13;31;25 24;18;36;30 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. Interestingly, addition of V82A to G48V\I54V increased IC50 68.1-fold, greater than the sum of the effects of each in the presence of NFV. 2016 PloS one Result HIV G48V;I54V;V82A 35;40;27 39;44;31 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. The V82A mutation, however, had no effect on RTV antiviral activity, and the G48V\I54V mutation reduced the slope but not the IC50. 2016 PloS one Result HIV G48V;I54V;V82A 77;82;4 81;86;8 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. These findings suggested that the interaction between V82A and G48V\I54V was synergistic. 2016 PloS one Result HIV G48V;I54V;V82A 63;68;54 67;72;58 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. While the mutation V82A had no effect on IC50, but reduced the slope of the dose-response curve for this agent. 2016 PloS one Result HIV V82A 19 23 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Considering the dramatic negative impact of Y135F on recognition of Nef134-8, we reasoned that the 7 patients who were Y135- provirus-negative and Tet-8-negative represented the most plausible candidates for having been infected with HIV-1 carrying Nef-Y135F. 2016 PloS one Result HIV Y135F;Y135F 44;253 49;258 Nef;Nef 68;249 71;252 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Finally, we stratified our A*24:02-positive individuals into those plausibly infected with HIV-1 containing the Nef-Y135F escape mutation (N = 7) and those for whom infection with global wild-type Y135 was probable (or could not be ruled out) (N = 18). 2016 PloS one Result HIV Y135F 116 121 Nef 112 115 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Furthermore, the Y135F mutation reduced binding of the 10mer epitope modestly, but it dramatically reduced binding of the 8mer. 2016 PloS one Result HIV Y135F 17 22 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. In contrast, 7 of 22 (32%) individuals in group 2 (plasma Y135F) harbored Y135 provirus at frequencies ranging from 0.06-45.27%, identifying these as possible Y135 transmission cases that had subsequently escaped to Y135F in vivo. 2016 PloS one Result HIV Y135F;Y135F 58;216 63;221 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Interestingly, of the 21 subgroup 2A patients who harbored Y135F with no additional substitutions in plasma HIV-1 RNA, 20 (95%) were Tet-10-positive while only 11/21 (52%) were Tet-8-positive (p = 0.0036, Fisher's exact test). 2016 PloS one Result HIV Y135F 59 64 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Interestingly, weak but significantly higher response than background level (about 20% of the Y135-containing wild type) of CTL clone C1-28, dually specific for Nef134-10(Y135) and Nef134-10(Y135F) (Fig 1C, right), was observed. 2016 PloS one Result HIV Y135F 191 196 Nef;Nef 161;181 164;184 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Luciferase readouts from the fusion constructs indicated that Y135F did not affect minigene transcription and translation (Fig 1B), however this mutation dramatically reduced epitope recognition by CTL clones known to be dually-specific for Y135 and Y135F-containing epitopes (Fig 1C). 2016 PloS one Result HIV Y135F;Y135F 62;250 67;255 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Nef codon 135 was unambiguously Y135 in 7/31 (23%) individuals (Group 1) or Y135F in 23/31 (74%) and Y135W in 1/31 (3%) (Group 2) (Fig 3). 2016 PloS one Result HIV Y135F;Y135W 76;101 81;106 Nef 0 3 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Notably however, the individuals inferred to have been infected with HIV-1 containing Nef-Y135F exhibited significantly lower CD4+ cell counts at all time intervals except the first visit (Fig 5B). 2016 PloS one Result HIV Y135F 90 95 Nef 86 89 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Similarly, the only patient within subgroup 2B (IMS0871), who harbored plasma Y135F with a C-terminal mutation in Nef134-10, was also Tet-10-negative and weakly Tet-8-positive. 2016 PloS one Result HIV Y135F 78 83 Nef 114 117 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Specifically, the introduction of Y135F into the minigene abolished the response of CTL clone T26-102, dually specific to Nef134-8(Y135) and Nef134-8(Y135F) (Fig 1C, left), to the background level. 2016 PloS one Result HIV Y135F;Y135F 34;150 39;155 Nef;Nef 122;141 125;144 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Subgroups 1A/2A included 23 (74%) individuals who harboured the global wild-type Nef134-10 epitope sequence with or without Y135F (RYPLTFGWCF or RFPLTFGWCF). 2016 PloS one Result HIV Y135F 124 129 Nef 81 84 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Subgroups 1C/2C included 5 (16%) individuals with substitutions other than Y135F at codon 2 and/or substitutions at central epitope sites. 2016 PloS one Result HIV Y135F 75 80 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Taken together with the observations described above, we inferred that Tet-8-negative responses in this group could reflect two possibilities: either loss of immune memory following Y135-to-Y135F selection in vivo (in which case archived Y135 proviruses should be detectable in these patients) or lack of responsiveness to this epitope as a result of infection with HIV-1 containing Y135F. 2016 PloS one Result HIV Y135F;Y135F 190;383 195;388 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. The potential ability of proviral DNA analysis to infer the sequence of the transmitting strain was tested in patient IMS0509 whose initial Y135 plasma viruses were replaced by Y135F variants by week 58: in this patient, Y135-containing proviral sequences could still be detected at 2.75% frequency >12 years later (data not shown). 2016 PloS one Result HIV Y135F 177 182 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. The remaining 15 of 22 (68%) individuals with plasma Y135F harbored no detectable Y135 provirus. 2016 PloS one Result HIV Y135F 53 58 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. the two residues downstream of Nef134-8) with or without Y135F. 2016 PloS one Result HIV Y135F 57 62 Nef 31 34 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. The two subgroup 1A individuals subsequently escaped within Nef134-10 (IMS0671 developed Y135F while IMS0738 developed F139L, an escape mutation we identified previously) while the two subgroup 1B patients (IMS0525 and IMS0735) also selected Y135F later in their course. 2016 PloS one Result HIV F139L;Y135F;Y135F 119;89;242 124;94;247 Nef 60 63 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. This finding suggests possible Y135F transmission (though rapid replacement of Y135 sequences by replicating Y135F virus after selection in the infected host cannot be ruled out). 2016 PloS one Result HIV Y135F;Y135F 31;109 36;114 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. This suggests that in individuals infected with Y135F-containing HIV-1, presentation of Nef134-10(Y135F), but not Nef134-8(Y135F), may still occur. 2016 PloS one Result HIV Y135F;Y135F;Y135F 48;98;123 53;103;128 Nef;Nef 88;114 91;117 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Together, these results suggest that infection with Y135F-containing HIV-1 may be able to stimulate weak CTL responses to Nef134-10 but not to Nef134-8. 2016 PloS one Result HIV Y135F 52 57 Nef;Nef 122;143 125;146 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. We began by assessing the ability of these epitopes, with or without Y135F, to stimulate CTL responses in A*24:02-positive individuals. 2016 PloS one Result HIV Y135F 69 74 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. We first wished to infer how infection with Y135F-containing HIV might affect CTL responses to Nef134-8 and Nef134-10. 2016 PloS one Result HIV Y135F 44 49 Nef;Nef 95;108 98;111 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. We thus performed Nef proviral deep-sequencing for all patients except IMS0617 (who harbored Y135W) from PBMCs collected a median of 0 (IQR 0-19.5) weeks after the first visit (Fig 3). 2016 PloS one Result HIV Y135W 93 98 Nef 18 21 26977119 A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients. In striking contrast, the IL4R genotype A/A (I50V), when compared to the genotypes A/G and G/G, occurred more frequently among patients with high radiological severity scores for cavities compared to those with low ones (odds ratio (OR) 1.32, 95% confidence interval (CI) 1.0-1.7, p value 0.05). 2016 Mediators of inflammation Result HIV I50V 45 49 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. 1d) and E45A/R132T, A204C and A14C/E45C (not shown), with varying relative abundances of tubes and cones. 2016 Retrovirology Result HIV A14C;A204C;E45A;E45C;R132T 30;20;8;35;13 34;25;12;39;18 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. A cross-sectional analysis of representative WT and E45A cores is shown in. 2016 Retrovirology Result HIV E45A 52 56 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Interestingly, the effect of the additional hydrophobic interactions (from E45A-containing mutations) on the stiffness of the assembled CA is larger than that of the covalent disulfide bridge (from the A204C and A14C/E45C mutations). 2016 Retrovirology Result HIV A14C;A204C;E45A;E45C 212;202;75;217 216;207;79;221 Capsid 136 138 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. The A204C mutation introduces a crosslink between CA hexamers, whereas the A14C/E45C double mutation introduces a crosslink between CA monomers within the hexamer. 2016 Retrovirology Result HIV A14C;A204C;E45C 75;4;80 79;9;84 Capsid;Capsid 50;132 52;134 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. The double mutant E45A/R132T CA assemblies exhibited stiffness values of 0.146 +- 0.029 N/m (n = 16), which is similar to the stiffness of the single mutant. 2016 Retrovirology Result HIV E45A;R132T 18;23 22;28 Capsid 29 31 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. The same two forms were found for hyperstable mutant CA assemblies: E45A. 2016 Retrovirology Result HIV E45A 68 72 Capsid 53 55 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. The stiffness values for both mutants are, 0.077 +- 0.009 N/m (n = 32) and 0.102 +- 0.017 N/m (n = 36), for A204C and A14C/E45C, respectively. 2016 Retrovirology Result HIV A14C;A204C;E45C 118;108;123 122;113;127 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. We observed that the E45A mutation produced the stiffest capsid structures, with similar values for E45A CA assemblies (0.153 +- 0.02 N/m, n = 19) and for isolated cores (0.152 +- 0.037 N/m, n = 19). 2016 Retrovirology Result HIV E45A;E45A 21;100 25;104 Capsid;Capsid 57;105 63;107 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. We then measured two CA variants that contain the E45A mutation. 2016 Retrovirology Result HIV E45A 50 54 Capsid 21 23 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. Of these, the most common were K103N, V106M, and G190A occurring in 27 (3.9%), 3 (0.4%), and 2 (0.3%) participants, respectively. 2016 AIDS research and human retroviruses Result HIV G190A;K103N;V106M 49;31;38 54;36;43 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. Of those with NRTI mutations, five (0.7%) had only the M184V mutation, two (0.3%) had the K65R mutation alone, one (0.1%) had the M41L mutation alone, and two (0.3%) had multiple thymidine analogue mutations (one with M184V). 2016 AIDS research and human retroviruses Result HIV K65R;M184V;M184V;M41L 90;55;218;130 94;60;223;134 NRTI 14 18 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. Six (0.9%) participants had both NNRTI and NRTI resistance mutations, K103N+M184V being the most common combination. 2016 AIDS research and human retroviruses Result HIV K103N;M184V 70;76 75;81 NNRTI;NRTI 33;43 38;47 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. Twelve of the 15 had a single NNRTI mutation (10 with K103N, 1 with V106M, and 1 with G190A) (Supplementary Table S1. 2016 AIDS research and human retroviruses Result HIV G190A;K103N;V106M 86;54;68 91;59;73 NNRTI 30 35 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Although PR20 bears major DRV resistance mutations V32I, I47V, I54L, there are no corresponding mutations in PRS17 to explain the similar Ki values shown by these 2 enzymes. 2016 Biochemistry Result HIV I47V;I54L;V32I 57;63;51 61;67;55 PR;PR 9;109 11;111 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Conservative substitutions L10V and L10I in PR22 and PRS17 respectively, are classified as minor resistance mutations. 2016 Biochemistry Result HIV L10I;L10V 36;27 40;31 PR;PR 44;53 46;55 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. I54L (in PR20) and I54V (in PRS17) are major mutations associated with high-level resistance to most PIs, with the possible exception of DRV (for I54V). 2016 Biochemistry Result HIV I54V;I54V;I54L 19;146;0 23;150;4 PI;PR;PR 101;9;28 104;11;30 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. In addition L90M, which confers major resistance to multiple drugs, is common to both PR20 and PRS17. 2016 Biochemistry Result HIV L90M 12 16 PR;PR 86;95 88;97 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. In contrast, mutations D30N, V32I, L33F, I47V, I54L, and I84V are present in PR20 but not in PRS17. 2016 Biochemistry Result HIV D30N;I47V;I54L;I84V;L33F;V32I 23;41;47;57;35;29 27;45;51;61;39;33 PR;PR 77;93 79;95 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. L63P has been identified in drug resistant PR mutants and is classified as a minor drug resistance mutation, possibly associated with resistance to LPV. 2016 Biochemistry Result HIV L63P 0 4 PR 43 45 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Mutations I62V and L63P in cluster 2 are common to PR20 and PRS17, and interestingly, also occur naturally in PR group O. 2016 Biochemistry Result HIV I62V;L63P 10;19 14;23 PR;PR;PR 51;60;110 53;62;112 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Mutations in PRS17 associated with resistance to multiple drugs are M46L, G48V, I54V, V82S and L90M. 2016 Biochemistry Result HIV G48V;I54V;L90M;M46L;V82S 74;80;95;68;86 78;84;99;72;90 PR 13 15 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Of these, I54V and L90M are major drug resistance mutations. 2016 Biochemistry Result HIV I54V;L90M 10;19 14;23 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Only five of the mutations in PR22 are identical with those in PRS17, namely, E35D, M36I, S37D, I54V, and L90M. 2016 Biochemistry Result HIV E35D;I54V;L90M;M36I;S37D 78;96;106;84;90 82;100;110;88;94 PR;PR 30;63 32;65 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Other mutations in this region, E35D and M36I in both mutants, and S37D in PRS17, are located in the flap hinge loop and likely contribute to altered flap conformation and dynamics. 2016 Biochemistry Result HIV E35D;M36I;S37D 32;41;67 36;45;71 PR 75 77 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Outside of the clusters, mutations L10F in PR20 and possibly L10I in PRS17 could disrupt the ion pair between R8 and D29' of the opposite subunit, resulting in altered conformation of the binding cavity. 2016 Biochemistry Result HIV L10F;L10I 35;61 39;65 PR;PR 43;69 45;71 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. PR20 and PRS17 have six mutations in common including L90M in cluster 3 associated with resistance to all PIs used in this study except TPV and DRV. 2016 Biochemistry Result HIV L90M 54 58 PI;PR;PR 106;0;9 109;2;11 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. PR20 cluster 1 encompasses three mutations contiguous to the active site, D30N, V32I and L33F, that are not present in PRS17. 2016 Biochemistry Result HIV D30N;L33F;V32I 74;89;80 78;93;84 PR;PR 0;119 2;121 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Similarly SQV binds to PRS17 with ~10-fold poorer affinity relative to PR20, possibly also reflecting effects of SQV resistance-associated mutations G48V and I54V in PRS17 which are not present in PR20. 2016 Biochemistry Result HIV G48V;I54V 149;158 153;162 PR;PR;PR;PR 23;71;166;197 25;73;168;199 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. This difference may relate to major APV drug resistance mutations V32I, I47V, I84V present in PR20 but not in PRS17 (see Table S1). 2016 Biochemistry Result HIV I47V;I84V;V32I 72;78;66 76;82;70 PR;PR 94;110 96;112 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Unlike mutations V82S, proximal to the active site pocket, and G48V and I54V in the flap regions, non-active site mutations L90M and A71V may indirectly influence inhibitor or substrate binding. 2016 Biochemistry Result HIV A71V;G48V;I54V;L90M;V82S 133;63;72;124;17 137;67;76;128;21 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. With the exception of L90M these mutations are not present in PR20. 2016 Biochemistry Result HIV L90M 22 26 PR 62 64 27039930 Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme. Within this group of 8 mutations, the conservative substitutions I54L (in PR20) and I54V (in PRS17) have similar but not identical drug-resistance profiles. 2016 Biochemistry Result HIV I54L;I54V 65;84 69;88 PR;PR 74;93 76;95 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. A computational study was performed to demonstrate how the introduction or modification of a R1 substituent could contribute to overcoming E138K-induced drug resistance to 1b. 2016 Journal of medicinal chemistry Result HIV E138K 139 144 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Again, the latter result is highly desirable for combating resistance in the E138K mutant virus. 2016 Journal of medicinal chemistry Result HIV E138K 77 82 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. All new DAAN compounds (6, 13, and 14 series) were evaluated against wild-type HIV-1 (NL4-3 and IIIB) and resistant viral strain (E138K, A17, and K101E) replication in TZM-bl (NL4-3 and E138K) and MT-2 (IIIB) cell lines, respectively. 2016 Journal of medicinal chemistry Result HIV E138K;E138K;K101E 130;186;146 135;191;151 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. As shown in Figure 3, the docking poses of 6a (green) and 1b (gray) in both 3MEC (wild-type) and 2HNY (E138K mutant) structures, respectively, displayed similar binding orientations with "U"-like conformational shapes and two characteristic hydrogen bonds formed with the key amino acid K101, consistent with prior results and literature reports on 1b. 2016 Journal of medicinal chemistry Result HIV E138K 103 109 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Comparison of the results in the wild-type NL4-3 and drug-resistant E138K assays identified the most promising compounds as 6a, 6b, 14c, and 14d, as indicated by low resistance FCs of 1.9-2.2, which were much better than that of 1b (FC = 10), lower than those of the other new DAANs, and comparable with those of the prior 2c (FC = 1.7) and 2d (FC = 3.7) in the same assay. 2016 Journal of medicinal chemistry Result HIV E138K 68 73 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Despite their high potency (EC50 = 0.53-3.3 nM) against wild-type NL4-3 virus, these compounds were much less potent against the E138K viral strain (EC50 > 13.3-39 nM), leading to poorer resistance FC values of 9-48 compared with those of 6a, 6b, 14c, and 14d. 2016 Journal of medicinal chemistry Result HIV E138K 129 134 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. In addition, representative compounds 6b, 6p, and 2d, which had markedly improved drug-resistant profiles for the E138K mutant, were tested against another 1b-resistant viral strain, K101E. 2016 Journal of medicinal chemistry Result HIV E138K;K101E 114;183 119;188 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Moreover, eight active compounds (EC50 < 5 nM against IIIB) were further tested in the MT-2 cell line against the multi-NRTI-resistant A17 viral strain with mutants K103N and Y181C, the two major mutants from the first-generation NNRTI drugs. 2016 Journal of medicinal chemistry Result HIV K103N;Y181C 165;175 170;180 NNRTI;NRTI 230;120 235;124 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. The compounds were docked computationally to both wild-type RT/1b [Protein Data Bank (PDB) entry 3MEC] and mutated E138K RT/nevirapine (PDB entry 2HNY) complex crystal structures. 2016 Journal of medicinal chemistry Result HIV E138K 115 120 RT;RT 60;121 62;123 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Thus, the presence of a conjugated carbonyl group in R1 on the B-ring is favorable against the E138K drug 1b resistance. 2016 Journal of medicinal chemistry Result HIV E138K 95 100 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Thus, this carbonyl group might be important for inhibiting the E138K mutation, possibly because it could interact with the mutated K138 or nearby amino acid(s). 2016 Journal of medicinal chemistry Result HIV E138K 64 69 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. To evaluate our hypothesis concerning a possible link between the R1 substituent of a compound and its effectiveness against NNRTI-resistant virus, active DAAN compounds were tested against the E138K mutated viral strain, which has a major mutation conferring resistance to 1b, and the data are summarized in Table 1. 2016 Journal of medicinal chemistry Result HIV E138K 194 199 NNRTI 125 130 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. According to our result, the 2 pairs of alleles were called simultaneously in 145 out of 159 specimens for K101E/Q/P (91.2% of the total specimens) and in 143 out of 159 specimens (89.9% of the total specimens) for K103N/S. 2016 PloS one Result HIV K101E;K101P;K101Q;K103N;K103S 107;107;107;215;215 116;116;116;222;222 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. Although the call rate per sample was not completely ideal, the assay was able to detect major resistance mutations (M41L, K65R, M184V and G190A) in 150 out of 159 (94.3%) specimens simultaneously. 2016 PloS one Result HIV G190A;K65R;M184V;M41L 139;123;129;117 144;127;134;121 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. As shown in Table 2, 9 out of 10 alleles except L210W achieved a call rate greater than 90%. 2016 PloS one Result HIV L210W 48 53 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. Representative results demonstrating the concordance between the chromatograms of DNA sequencing and the MALDI-TOF MS results at two different drug resistance mutation sites (M184V and K103N) are shown in Fig 4A. 2016 PloS one Result HIV K103N;M184V 185;175 190;181 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. Since 2 simultaneous point mutations were required for converting the lysine (K) into glutamic acid (E), glutamine (Q) or proline (P) in codon 101 and asparagine (N) or serine (S) in codon 103, 2 alleles were required to be called simultaneously in order to give conclusive results for K101E/Q/P and K103N/S. 2016 PloS one Result HIV K101E;K101P;K101Q;K103N;K103S;P101P;S103S 286;286;286;300;300;119;166 295;295;295;307;307;149;193 27107820 HIV-1 capsid is involved in post-nuclear entry steps. A105S and N74D capsid mutants were both resistant to the integration block mediated by C-A1. 2016 Retrovirology Result HIV N74D;A105S 10;0 14;5 Capsid 15 21 27107820 HIV-1 capsid is involved in post-nuclear entry steps. CsA washout assays were then performed with wild type (WT) or capsid mutant N74D and A105S HIVGFP vectors to control for specificity. 2016 Retrovirology Result HIV A105S;N74D 85;76 90;80 Capsid 62 68 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Data from four independent experiments were collected: the average +-SEM ToU50 for WT HIV-1GFP was 110 +- 16 min, for the N74D virus was 88 +- 16 min and for the A105S virus was 92 +- 31 min. 2016 Retrovirology Result HIV A105S;N74D 162;122 167;126 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Furthermore, rescue of infection was clearly capsid-specific because it could not be detected with the N74D virus, which indeed showed no nuclear capsid upon cell fractionation. 2016 Retrovirology Result HIV N74D 103 107 Capsid;Capsid 45;146 51;152 27107820 HIV-1 capsid is involved in post-nuclear entry steps. However the kinetics of HIV-1 uncoating appear to be cell type dependent, hence we have adapted the assay in CD4+ Jurkat T cells stably expressing an engineered form of the human TRIM5alpha protein fused with CypA at position S322 (T5Cyp) or a mutant version that does not bind to capsid and cannot restrict infection (H126Q). 2016 Retrovirology Result HIV H126Q 319 324 Capsid 281 287 27107820 HIV-1 capsid is involved in post-nuclear entry steps. In cells infected with the N74D virus, virtually no capsid was detected in the nuclei, irrespective of Nup153. 2016 Retrovirology Result HIV N74D 27 31 Capsid 52 58 27107820 HIV-1 capsid is involved in post-nuclear entry steps. In H126Q cells, CsA weakly inhibited infection whereas in T5Cyp cells it rescued infection at concentrations >0.6 muM reaching a plateau at about 1.25 muM (Additional file 3. 2016 Retrovirology Result HIV H126Q 3 8 27107820 HIV-1 capsid is involved in post-nuclear entry steps. In parallel, we also tested the N74D mutation, which confers partial resistance to the small compound PF-74. 2016 Retrovirology Result HIV N74D 32 36 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Neither CsA nor C-A1 significantly affected the levels of infection over time in control H126Q cells (Additional file 4. 2016 Retrovirology Result HIV H126Q 89 94 27107820 HIV-1 capsid is involved in post-nuclear entry steps. T5Cyp cells showed a 10-fold restriction compared to H126Q cells with an almost linear dose-response curve within the 0.3-3 % infection range (T5Cyp cells) or 0.5-19 % range (H126Q) (Additional file 3. 2016 Retrovirology Result HIV H126Q;H126Q 53;175 58;180 27107820 HIV-1 capsid is involved in post-nuclear entry steps. The A105S and N74D mutations confer resistance to C-A1, suggesting that these residues are important for the antiretroviral effect of the drug. 2016 Retrovirology Result HIV A105S;N74D 4;14 9;18 27107820 HIV-1 capsid is involved in post-nuclear entry steps. The A105S and the N74D mutant viruses did not show significant accumulation of capsid into the nucleus, with or without C-A1, indicating that such viruses shed almost all of their capsid before nuclear entry. 2016 Retrovirology Result HIV A105S;N74D 4;18 9;22 Capsid;Capsid 79;180 85;186 27107820 HIV-1 capsid is involved in post-nuclear entry steps. The same results were obtained with N74D and A105S HIV-1GFP (Additional file 3. 2016 Retrovirology Result HIV A105S;N74D 45;36 50;40 27107820 HIV-1 capsid is involved in post-nuclear entry steps. To test if the effect of C-A1 was capsid-specific, we used a virus bearing the A105S capsid mutation. 2016 Retrovirology Result HIV A105S 79 84 Capsid;Capsid 34;85 40;91 27107820 HIV-1 capsid is involved in post-nuclear entry steps. To this end, T5Cyp and H126Q cells were infected in parallel with a fixed amount of HIV-1GFP in the presence of increasing concentrations of CsA. 2016 Retrovirology Result HIV H126Q 23 28 27107820 HIV-1 capsid is involved in post-nuclear entry steps. TRIMCyp and H126Q cells were infected on ice with HIV-1GFP virus (at an MOI 0.01-0.03) in the presence of 1 muM CsA or 3 muM C-A1. 2016 Retrovirology Result HIV H126Q 12 17 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Upon addition of C-A1, the ToU50 of WT HIV-1GFP was significantly shortened to approximately 34 +- 17 min, whereas ToU50 appeared higher for N74D (151 +- 23 min) and A105S (122 +- 40 min) viruses, although the difference did not reach statistical significance. 2016 Retrovirology Result HIV A105S;N74D 166;141 171;145 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Fifteen combinations were observed among 46 ARV drug-experienced subjects with 3 TAMs; where 39% of these subjects harbored the combination M41L + T215Y + L210W, followed in 11% by combination of D67N + K70R + K219Q. 2016 PloS one Result HIV D67N;K219Q;K70R;L210W;M41L;T215Y 196;210;203;155;140;147 200;215;207;160;144;152 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. For NNRTIs, the most common ADR-CRM and SDRM were K103N (69.0% and 4.0%, respectively) and P225H (27.2% and 2.0%, respectively) (Fig 1B). 2016 PloS one Result HIV K103N;P225H 50;91 55;96 NNRTI 4 10 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. For NRTIs, the most common ADR-CRM were M184VI (76.0%) and T215YF (26.8%), whereas the most common SDRM were T215 revertants (2.4%) and M41L (2.0%) (Fig 1A). 2016 PloS one Result HIV M184I;M184V;M41L;T215F;T215Y 40;40;136;59;59 46;46;140;65;65 NRTI 4 9 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. For PIs, the most frequent ADR-CRM were M46IL (3.6%), V82AT (3.2%), L90M (2.6%) and Q58E (2.1%) and, the only SDRM observed was M46L/I (1.5%) (Fig 1C). 2016 PloS one Result HIV L90M;M46I;M46I;M46L;M46L;Q58E;V82A;V82T 68;40;128;40;128;84;54;54 72;45;134;45;134;88;59;59 PI 4 7 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. In addition, K103N frequency was 23.3% in subjects under second-line scheme, the lowest observed among all schemes (Fig 3A-3E). 2016 PloS one Result HIV K103N 13 18 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. In ARV drug-experienced subjects presenting only one TAM, mutations T215Y (2.8%) and T215F (2.6%) were the most common; whereas, M41L (1.6%) was predominant in ARV drug-naive subjects (Fig 1E and 1F). 2016 PloS one Result HIV M41L;T215F;T215Y 129;85;68 133;90;73 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. In ARV drug-experienced subjects, TAMs found were T215Y/F (26.8%), K70R (15.2%), M41L (13.7%), K219E/Q (12.2%), D67N (10.9%), and L210W (7.5%) (Fig 1A). 2016 PloS one Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 112;95;95;67;130;81;50;50 116;102;102;71;135;85;57;57 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. In ARV drug-naive subjects, observed TAMs were T215rev (2.0%), T215F (0.4%), M41L (2.0%), K219EQ (0.4%) and L210W (0.4%) (Fig 1A). 2016 PloS one Result HIV K219E;K219Q;L210W;M41L;T215F 90;90;108;77;63 96;96;113;81;68 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Mutations associated with PIs were more observed at position M46IL and V82A in subjects on second-line and rescue schemes (Fig 3D and 3E). 2016 PloS one Result HIV M46I;M46L;V82A 61;61;71 66;66;75 PI 26 29 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Of the 42 ARV drug-experienced subjects with two TAMs, 11 different TAM combinations were observed; being TAMs combinations M41L + T215Y (40%) as the most common, followed by M41L + T215F (14%). 2016 PloS one Result HIV M41L;M41L;T215F;T215Y 124;175;182;131 128;179;187;136 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Only two ARV drug naive subjects harbored two TAMs (M41L and T215FD), whereas a substantial proportion of ARV drug-experienced subjects harbored two or three TAMs (Fig 1D). 2016 PloS one Result HIV M41L;T215D;T215F 52;61;61 57;67;67 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. The frequency and patterns of mutations differed slightly among individuals under first-line ART schemes; however, in all cases higher percentages of M184VI, K103N and P225H were observed (Fig 3A, 3B and 3C). 2016 PloS one Result HIV K103N;M184I;M184V;P225H 158;150;150;168 163;156;156;173 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. The highest percentage of NRTIs mutations in subjects on second-line scheme were M184V and T215FY in only 40.0% and 21.7% of the subjects compared to up to 88.0% and 83.0% respectively observed in subjects on other schemes. 2016 PloS one Result HIV M184V;T215F;T215Y 81;91;91 86;97;97 NRTI 26 31 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Another most common NNRTI-RAM detected in patients that failed EFV-based regimen was K103N (61.2%) compared to those that failed NVP-based regimen (18.5%; p<0.01). 2016 PloS one Result HIV K103N 85 90 NNRTI 20 25 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. For example, Y181C (52.7%) was the most common NNRTI-RAM detected in patients that failed NVP-based regimen compared to those that failed EFV-based regimen (14.0%; p<0.01). 2016 PloS one Result HIV Y181C 13 18 NNRTI 47 52 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Interestingly, the most prevalent NNRTI-RAM E138K reported in the ECHO and THRIVE studies were rarely detected in this study. 2016 PloS one Result HIV E138K 44 49 NNRTI 34 39 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Overall, the top 10 most common NNRTI-RAMs found in this study were V90I, followed by A98G, K101E, K103N, V108I, Y181C, M184I, Y188L, G190A and H221Y (Fig 1; listed according to the most frequently detected mutation to the least). 2016 PloS one Result HIV A98G;G190A;H221Y;K101E;K103N;M184I;V108I;V90I;Y181C;Y188L 86;134;144;92;99;120;106;68;113;127 90;139;149;97;104;125;111;72;118;132 NNRTI 32 37 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. The authors observed only 2 patients (0.4%) that failed EFV-based regimen had the E138K mutation and none from the failed NVP-based regimen (p = 0.03). 2016 PloS one Result HIV E138K 82 87 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. 4); K101P HIV-1 showed a slight increase in susceptibility to DOR (1.0 +- 0.27 nM) and a modest decrease in susceptibility to RPV (6.2 +- 1.6 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K101P 4 9 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. As described above, both compounds were tested against M230L (which should be similar to M230I). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV M230I;M230L 89;55 94;60 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. As expected, L234I (6.8 +- 2.5 nM) showed a modest reduction in susceptibility to DOR, while V106A showed a greater loss of susceptibility (15.6 +- 4 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV L234I;V106A 13;93 18;98 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Because many of the commonly used cART regimens include either 3TC or FTC, some isolates from virological failures also contained the M184V/I mutation. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V 134;134 141;141 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. DOR also showed a considerable loss of potency versus the resistant mutant Y188L, out of the range of our assay (>100 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV Y188L 75 80 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. DOR potently inhibited the replication of E40K, K101E, V111A, M184I, M184V, K101E/M184I, K101E/M184V, E138K/M184I, and E138K/M184V (all <3 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;E138K;E40K;K101E;K101E;K101E;M184I;M184I;M184I;M184V;M184V;M184V;V111A 102;119;42;48;76;89;62;82;108;69;95;125;55 107;124;46;53;81;94;67;87;113;74;100;130;60 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. DOR potently inhibited the replication of the WT HIV-1 vector in the single-cycle assay (0.67 +- 0.14 nM) and L100I mutant (1.14 +- 0.2 nM) as shown in. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV L100I 110 115 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. HIV-1 variants G190A, P236L, and L100I/K103N were susceptible to DOR (<2 nM), however the G190S mutant showed a modest reduction in susceptibility (4.6 +- 1.2 nM) while the M230L mutant and the K103N/P225H double mutant had substantial decreases in their respective susceptibilities (51.1 +- 6.5 nM and 25.3 +- 4.5 nM, respectively). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;G190S;K103N;K103N;L100I;M230L;P225H;P236L 15;90;39;194;33;173;200;22 20;95;44;199;38;178;205;27 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. However, the resistant mutants K103N, Y181C, and H221Y showed modest decreases in susceptibility against DOR (ranging from 2-5 nM), and the K103N/Y181C double mutant exhibited a larger drop in susceptibility (11.3 +- 5.9 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV H221Y;K103N;K103N;Y181C;Y181C 49;31;140;38;146 54;36;145;43;151 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. In addition, the triple mutant V106A/G190A/F227L was relatively insensitive to DOR (>100 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV F227L;G190A;V106A 43;37;31 48;42;36 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. In addition, we selected HIV-1 RT mutations in cell culture with a closely related RPV analog (unpublished observations): E40K, D67E, V111A, E138K, Y181C, and M230I. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV D67E;E138K;E40K;M230I;V111A;Y181C 128;141;122;159;134;148 132;146;126;164;139;153 RT 31 33 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Interestingly, the variant K101E was the only RPV-associated single mutant which conferred a small, but measurable decrease in susceptibility to RPV (2.6 +- 1.6 nM), while the rest of the mutants selected by RPV remained sensitive in our assay (< 1 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K101E 27 32 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. K101E is a mutation that is commonly selected in patients who fail regimens that include ETR, a compound that is structurally related to RPV, and that we selected with RPV in vitro. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K101E 0 5 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. RPV has been reported to select for another resistance pathway that involves K101P and Y181I, and K101P/V179I. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K101P;K101P;V179I;Y181I 77;98;104;87 82;103;109;92 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Some of the viruses selected by DOR in culture contained additional mutations: V106A/F227L, V106A/L234I, and V106A/F227L/L234I. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV F227L;L234I;V106A;F227L;L234I;V106A;V106A 115;121;109;85;98;79;92 120;126;114;90;103;84;97 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The ability of RPV to inhibit these E138K/M184I/V RT mutants in tissue culture has been reported previously. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K;M184I;M184V 36;42;42 41;49;49 RT 50 52 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The double and triple mutants V106A/F227L, V106/L234I, and V106A/F227L/L234I all showed a substantial loss of susceptibility to DOR (>100 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV F227L;L234I;V106A;L234I;F227L;V106A 65;71;59;48;36;30 70;76;64;53;41;35 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The double mutant K101P/V179I showed an increase in susceptibility to DOR (1.5 +- 0.4 nM); however, this mutant had a significant loss in susceptibility to RPV (93.5 +- 12.1 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K101P;V179I 18;24 23;29 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The E138K mutant showed a modest decrease in susceptibility to DOR (13.9 +- 2.4 nM), while D67E variant showed a larger decrease in susceptibility (46 +- 14 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV D67E;E138K 91;4 95;9 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The E138K substitution in RT is the most common NNRTI-resistance mutation seen in patients who fail RPV-containing regimens. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV E138K 4 9 NNRTI;RT 48;26 53;28 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The effects of Y181C on the susceptibility of the vector to DOR and RPV were discussed earlier. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181C 15 20 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The Y181I mutant was also sensitive to DOR (0.63 +- 0.28 nM) but this mutant showed a reduced susceptibility to RPV (8.8 +- 0.12 nM). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV Y181I 4 9 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. To determine whether there is cross resistance between RPV and DOR and to further compare the overall effectiveness of the compounds, RPV and DOR were screened against the following mutants: V106A, L234I, V106A/F227L, V106/L234I, and V106A/F227L/L234I. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV F227L;L234I;V106A;L234I;F227L;L234I;V106A;V106A 240;246;234;223;211;198;191;205 245;251;239;228;216;203;196;210 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. V106A was the major variant selected by DOR treatment of HIV-1 in cultured cells. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV V106A 0 5 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. We chose NNRTI resistant mutants that are known to contribute to virological failure in HIV-infected individuals or mutants that were selected in cell culture: G190A, G190S, M230L, P236L, L100I/K103N, K103N/P225H, and V106A/G190A/F227L. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV F227L;G190A;V106A;G190A;G190S;K103N;K103N;L100I;M230L;P225H;P236L 230;224;218;160;167;194;201;188;174;207;181 235;229;223;165;172;199;206;193;179;212;186 NNRTI 9 14 HIV infections 88 100 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. We initially investigated the L100I, K103N, Y181C, Y188L, H221Y, and K103N/Y181C RT mutants. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV H221Y;K103N;K103N;L100I;Y181C;Y181C;Y188L 58;37;69;30;44;75;51 63;42;74;35;49;80;56 RT 81 83 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. We screened a panel of mutants that included: E40K, D67E, K101E, V111A, E138K, M184I, M184V, K101E/M184I, K101E/M184V, E138K/M184I, and E138K/M184V. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV D67E;E138K;E138K;E138K;E40K;K101E;K101E;K101E;M184I;M184I;M184I;M184V;M184V;M184V;V111A 52;72;119;136;46;58;93;106;79;99;125;86;112;142;65 56;77;124;141;50;63;98;111;84;104;130;91;117;147;70 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. 1c) viruses compared to L74V and K103N alone, respectively. 2016 Retrovirology Result HIV K103N;L74V 33;24 38;28 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. 1d), whereas only slight decreases, about 1.2-fold were observed for R263K-L74V. 2016 Retrovirology Result HIV L74V;R263K 75;69 79;74 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. 3a, b, f), or undetectable levels in H51Y/R263K-K103N, H51Y/R263K-E138K and H51Y/R263K-M184I viruses. 2016 Retrovirology Result HIV E138K;H51Y;H51Y;H51Y;K103N;M184I;R263K;R263K;R263K 66;37;55;76;48;87;42;60;81 71;41;59;80;53;92;47;65;86 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. As previously hypothesized, the fitness cost of the H5Y/R263K combination may have a benefit for patients under DTG treatment in terms of viral load. 2016 Retrovirology Result HIV H5Y;R263K 52;56 55;61 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. First, we created chimeric HIVs having R263K or both H51Y/R263K in IN together with any of a number of major RTI-resistance substitutions. 2016 Retrovirology Result HIV H51Y;R263K;R263K 53;39;58 57;44;63 RT;IN 109;67 112;69 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Given the current co-administration of DTG with RTIs for HIV treatment, we wanted to determine whether the R263K and H51Y/R263K mutations may have similar effects on viruses that contained mutations in RT that confer resistance to RTIs. 2016 Retrovirology Result HIV H51Y;R263K;R263K 117;107;122 121;112;127 RT;RT;RT 48;231;202 52;235;204 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. H51Y/R263K were very impaired in replication (P < 0.05). 2016 Retrovirology Result HIV R263K;H51Y 5;0 10;4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. However, the viruses that contained H51Y/R263K plus a RT mutation or only H51Y/R263K were unable to generate detectable p24 at day 7, suggesting that significant replication had not occurred. 2016 Retrovirology Result HIV H51Y;H51Y;R263K;R263K 36;74;41;79 40;78;46;84 p24;RT 120;54 123;56 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. However, this trend did not reach statistical significance for the K65R versus H51Y/R263K-K65R viruses (P = 0.08). 2016 Retrovirology Result HIV H51Y;K65R;K65R;R263K 79;67;90;84 83;71;94;89 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In both experiments, the L74V and K103N viruses were the least affected by the presence of H51Y/R263K or R263K. 2016 Retrovirology Result HIV H51Y;K103N;L74V;R263K;R263K 91;34;25;96;105 95;39;29;101;110 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In contrast, none of the R263K-containing viruses produced detectable p24 in our assay until day 7 p.i. 2016 Retrovirology Result HIV R263K 25 30 p24 70 73 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In viruses carrying K65R, E138K, or M184V, the additional presence of R263K in IN coding sequence caused a further impact on viral replication than was associated with any of these RT mutations on their own. 2016 Retrovirology Result HIV E138K;K65R;M184V;R263K 26;20;36;70 31;24;41;75 IN;RT 79;181 81;183 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Our results show that the addition of R263K to the K65R-, L74V-, K103N-, E138K-, or M184I/V-harbouring viruses resulted in further moderate decreases in viral infectivity ranging from 1.23-fold to 3.17-fold (P < 0.05), depending on the RT backbone. 2016 Retrovirology Result HIV E138K;K103N;K65R;L74V;M184I;M184V;R263K 73;65;51;58;84;84;38 78;70;55;62;91;91;43 RT 236 238 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. R263K on its own together with any one of the RT mutations in the same virus yielded only slight reductions in viral infectivity compared to either mutation alone, and the presence of both H51Y/R263K together with the RT mutations had the most severe consequence on infectiousness. 2016 Retrovirology Result HIV H51Y;R263K;R263K 189;194;0 193;199;5 RT;RT 46;218 48;220 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Results from the Alu-mediated qPCR studies of viruses containing H51Y/R263K showed low levels of integrated DNA in cases of these viruses H51Y/R263K-K65R, H51Y/R263K-L74V and H51Y/R263K-M184V. 2016 Retrovirology Result HIV H51Y;H51Y;H51Y;H51Y;K65R;L74V;M184V;R263K;R263K;R263K;R263K 65;138;155;175;149;166;186;70;143;160;180 69;142;159;179;153;170;191;75;148;165;185 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The addition of double mutations H51Y/R263K to the L74V or K103N viruses also affected viral replication but at lower levels. 2016 Retrovirology Result HIV H51Y;K103N;L74V;R263K 33;59;51;38 37;64;55;43 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The addition of DTG-resistance substitutions reduces viral infectiousness in viruses containing the K65R, L74V, K103N, E138K or M184V/I reverse transcriptase mutations. 2016 Retrovirology Result HIV E138K;K103N;K65R;L74V;M184I;M184V 119;112;100;106;128;128 124;117;104;110;135;135 RT 136 157 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The most negative impact observed was when R263K was combined with E138K, yielding a 3.2-fold decrease in infectiousness compared to E138K alone. 2016 Retrovirology Result HIV E138K;E138K;R263K 67;133;43 72;138;48 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The order of diminished infectiousness with H51Y/R263K was as follows: E138K, relative fold-change (FC) = 10.4. 2016 Retrovirology Result HIV E138K;H51Y;R263K 71;44;49 76;48;54 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The results show that all the RTI-resistant viruses that also contained R263K exhibited slightly decreased levels of viral integration capacity, about 0.1 log-0.5 log reduction, compared to the single RT mutation viruses and WT. 2016 Retrovirology Result HIV R263K 72 77 RT;RT 30;201 33;203 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. These data are consistent with previous findings that reported that the presence of R263K in combination with M184I/V resulted in a further 1.8-fold decrease in replication capacity compared to M184I or M184V alone. 2016 Retrovirology Result HIV M184I;M184I;M184V;M184V;R263K 110;194;110;203;84 117;199;117;208;89 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. These results from replication kinetics over a 7-day period of infection lend support to the observation that the presence of R263K or H51Y/R263K in the IN sequence together with K65R, L74V, K103N, E138K, or M184V/I in the same virus resulted in slight to significant decreases in viral replication capacity. 2016 Retrovirology Result HIV E138K;H51Y;K103N;K65R;L74V;M184I;M184V;R263K;R263K 198;135;191;179;185;208;208;126;140 203;139;196;183;189;215;215;131;145 IN 153 155 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. We also conducted RT assays to validate our p24 results and found that a comparison of results from RT and p24 assays yielded similar findings for WT or viruses containing the R263K or H51Y/R263K substitutions (Table 1), but not for viruses containing mutations in the RT sequence (data not shown). 2016 Retrovirology Result HIV H51Y;R263K;R263K 185;176;190 189;181;195 p24;p24;RT;RT;RT 44;107;18;100;269 47;110;20;102;271 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. At failure, N155H was detected in four patients, and other secondary mutations were detected in five patients (71.4 %). 2016 BMC infectious diseases Result HIV N155H 12 17 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. 19/28, 68% with K65R on NVP), age, subtype, or time on treatment. 2016 Journal of the International AIDS Society Result HIV K65R 16 20 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. 2/11, 18%, without; p=0.002); G190A/S (12/24, 50%, with K65R vs. 2016 Journal of the International AIDS Society Result HIV G190A;G190S;K65R 30;30;56 37;37;60 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Compared to those without K65R, those with this mutation had lower median CD4 values (74 versus 269, p=0.019; 7% vs. 2016 Journal of the International AIDS Society Result HIV K65R 26 30 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K65R developed in 69% (24/35) of patients (Figure 2): 17/24 (71%) patients with subtype A, 4/4 (100%) subtype C, 2/4 (50%) subtype D and 1/3 (33%) AD recombinants (p=0.223). 2016 Journal of the International AIDS Society Result HIV K65R 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Mutations associated with K65R included Y181C (19/24, 79%, with K65R vs. 2016 Journal of the International AIDS Society Result HIV K65R;K65R;Y181C 26;64;40 30;68;45 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Only 4/24 patients with K65R had any IAS-USA-defined thymidine analogue mutations (TAMs). 2016 Journal of the International AIDS Society Result HIV K65R 24 28 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Other common (>20%) RT mutations were NRTI-associated M184V/I (27/35, 77%) and NNRTI-associated Y181C/G/Y (22/35, 63%), G190A/S (13/35, 37%) and K103N/S (11/35, 31%). 2016 Journal of the International AIDS Society Result HIV G190A;G190S;K103N;K103S;M184I;M184V;Y181C;Y181G;Y181Y 120;120;145;145;54;54;96;96;96 127;127;152;152;61;61;105;105;105 NNRTI;NRTI;RT 79;38;20 84;42;22 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. TDF-associated K70E was found in 3/35 (9%) patients, none with TAMs. 2016 Journal of the International AIDS Society Result HIV K70E 15 19 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. The most common codons of the wild type amino acid lysine (K) at position 64 were similar among subtypes A (AAG 96%), B (AAG 95%) and D (AAG 96%), and differed from subtype C (AAA 96%) in treatment-naive and -experienced patients from both Stanford and AMPATH. 2016 Journal of the International AIDS Society Result HIV K64K 48 79 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. The poly-adenosine AAA codon at position 64, thought to promote K65R development in subtype C, was present in only 1.0% of subtype A naive (1% Stanford, 0% AMPATH) and 1.7% of subtype D (1.7% Stanford, 0% AMPATH) sequences. 2016 Journal of the International AIDS Society Result HIV K65R 64 68 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. There was no significant association between K65R development and specific NNRTIs (5/7, 71% with K65R on EFV vs. 2016 Journal of the International AIDS Society Result HIV K65R;K65R 45;97 49;101 NNRTI 75 81 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. As shown in Figure 5C, the key distances, which can symbolize the binding between residues and inhibitor, are larger in D30N than in the WT. 2016 International journal of molecular sciences Result HIV D30N 120 124 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. However, the averaged distances over the last 40 ns of MD are 5.92 and 7.63 A for the WT and I50V complexes, respectively (Figure 6). 2016 International journal of molecular sciences Result HIV I50V 93 97 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. However, the decomposition of free energy shows that the electrostatic contribution of residue 30 in D30N is more favorable than in the WT. 2016 International journal of molecular sciences Result HIV D30N 101 105 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. Of course, the other mutations (D30N, I54M, and V82A) also cause the redistribution of their nearby residues. 2016 International journal of molecular sciences Result HIV D30N;I54M;V82A 32;38;48 36;42;52 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. So the distances between the two CA atoms of Val50 and Val50' become larger in the I50V complex relative to in the WT complex. 2016 International journal of molecular sciences Result HIV I50V 83 87 Capsid 33 35 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The averaged RMSDs values of D30N, I50V, I54M, and V82A are 1.42, 1.21, 1.36, and 1.07 A, respectively. 2016 International journal of molecular sciences Result HIV D30N;I50V;I54M;V82A 29;35;41;51 33;39;45;55 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The averaged value of psi angles of residue 50 in chain B of WT and I50V systems are 133.36 and -42.28 , respectively. 2016 International journal of molecular sciences Result HIV I50V 68 72 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The calculated binding free energies are -23.79, -20.72, -19.65, -21.18, and -21.86 kcal/mol for WT, D30N, I50V, I54M, and V82A complexes, respectively. 2016 International journal of molecular sciences Result HIV D30N;I50V;I54M;V82A 101;107;113;123 105;111;117;127 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The comparisons show that several residues contribute less in one complex relative to any other complex, such as Ala28 in D30N, Ile50' and Gly49' in I50V, and Asp29 in I54M. 2016 International journal of molecular sciences Result HIV D30N;I50V;I54M 122;149;168 126;153;172 Asp 159 162 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The DeltaGele is obviously larger in the WT than in each mutation, especially in the D30N. 2016 International journal of molecular sciences Result HIV D30N 85 89 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The DeltaGvdW of D30N is the strongest among all five complexes. 2016 International journal of molecular sciences Result HIV D30N 17 21 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The distances between two carbon atoms CA of residue 50 in both chains are 6.00 and 6.09 A in the crystallographic structures of WT and I50V, respectively. 2016 International journal of molecular sciences Result HIV I50V 136 140 Capsid 39 41 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The drug resistance of D30N mutation comes from the weak binding affinity for residues 28 and 29 of chain A in D30N relative to the WT. 2016 International journal of molecular sciences Result HIV D30N;D30N 23;111 27;115 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The entropic contribution also plays an important role in the I50V because the entropic contribution in I50V is obviously larger than in the WT. 2016 International journal of molecular sciences Result HIV I50V;I50V 62;104 66;108 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The free energy of residue 50 in chain A of the WT complex is more favorable than in the I50V complex, but not in chain B. 2016 International journal of molecular sciences Result HIV I50V 89 93 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The hydrogen bond analysis shows that the hydrogen bonds between the bridging water molecule and these two residues in I50V complex are weaker than in the WT complex (Table 3). 2016 International journal of molecular sciences Result HIV I50V 119 123 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The hydrogen bond between oxygen atom O6 of the inhibitor and the nitrogen atom of the backbone of residue 30 in chain A of the WT with 90.4% occupancy is stronger than in D30N complex with 77.4% occupancy (Table 3). 2016 International journal of molecular sciences Result HIV D30N 172 176 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The hydrogen bond between the backbone nitrogen atom of Asp29 and the O6 atom of the inhibitor in I54M is weaker in the WT (Table 3). 2016 International journal of molecular sciences Result HIV I54M 98 102 Asp 56 59 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The interaction energy of Asp29 is obviously weaker in I54M than in the WT. 2016 International journal of molecular sciences Result HIV I54M 55 59 Asp 26 29 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The isopropyl group of residue 82 in the WT complex is replaced by a methyl in the V82A complex. 2016 International journal of molecular sciences Result HIV V82A 83 87 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The Met54' showed two alternative conformations (major and minor) in the crystallographic structure of I54M. 2016 International journal of molecular sciences Result HIV I54M 103 107 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The minimum distances in the WT complex are larger than in the I50V complex for residue in chain A and vice versa in chain B. 2016 International journal of molecular sciences Result HIV I50V 63 67 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The side chains of Ala82/Ala82' in the V82A complex are smaller and lead to the loss of van der Waals interaction compared with those of Val82/ Val82 in the WT complex. 2016 International journal of molecular sciences Result HIV V82A 39 43 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The two conformations were observed for both Met54' and Met54 in the MD simulation of I54M. 2016 International journal of molecular sciences Result HIV I54M 86 90 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. This implies that mutations Ile50 to Val50 hardly affect the relative location of residues around Val50. 2016 International journal of molecular sciences Result HIV I50V 28 42 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. This implies that the conformation of WT is slightly different from the four mutations in some regions, especially for D30N and I54M. 2016 International journal of molecular sciences Result HIV D30N;I54M 119;128 123;132 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. This implies that the hydrophobic core in I54M becomes flexible relative to the WT complex. 2016 International journal of molecular sciences Result HIV I54M 42 46 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. To show the influence by the mutation of residue 54, we have calculated the averaged RMSDs of the heavy atom of the hydrophobic core in I54M (0.78 A) and in the WT (0.68 A). 2016 International journal of molecular sciences Result HIV I54M 136 140 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. CypA gene disruption had no major effects on the infectivities of wild-type or P90A mutant virus in the absence of IFN-alpha stimulation. 2016 Journal of virology Result HIV P90A 79 83 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. For instance, in MDMs pretreated with 62.5 U of IFN-alpha/ml, N74D or P90A CA mutants were inhibited ~20-fold, whereas wild-type HIV-1 GFP LV was blocked ~4-fold. 2016 Journal of virology Result HIV N74D;P90A 62;70 66;74 Capsid 75 77 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. HIV-1 CA mutants N74D or P90A display enhanced sensitivity to IFN-alpha-induced blocks. 2016 Journal of virology Result HIV N74D;P90A 17;25 21;29 Capsid 6 8 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. IFN-alpha induces an enhanced block to reverse transcription and nuclear import of HIV-1 CA N74D. 2016 Journal of virology Result HIV N74D 92 96 RT;Capsid 39;89 60;91 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. In both cell types, the N74D or P90A CA mutants were inhibited more effectively by pretreatment with lower doses of IFN-alpha relative to wild-type virus. 2016 Journal of virology Result HIV N74D;P90A 24;32 28;36 Capsid 37 39 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. In contrast, infectivity of the N74D mutant decreased in IFN-alpha-stimulated parental THP-1 cells ~43-fold and in MX2g1-1 and MX2g2-4 cells ~20-fold. 2016 Journal of virology Result HIV N74D 32 36 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. In contrast, the CA mutants N74D or P90A were suppressed up to ~10-fold more efficiently by pretreatment with different concentrations of IFN-alpha. 2016 Journal of virology Result HIV N74D;P90A 28;36 32;40 Capsid 17 19 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. In contrast, the levels of GFP reverse transcription products for HIV-1 CA N74D were reduced after IFN-alpha treatment ~8-fold and were not substantially different in MX2g2-4 cells compared to parental THP-1. 2016 Journal of virology Result HIV N74D 75 79 RT;Capsid 31;72 52;74 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. In primary CD4+ T cells, CA mutants N74D or P90A were blocked ~3-fold more than the wild-type virus at low IFN-alpha doses. 2016 Journal of virology Result HIV N74D;P90A 36;44 40;48 Capsid 25 27 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Like N74D or P90A, HIV-1 A105T was less sensitive to inhibition by ectopically expressed MX2 (data not shown). 2016 Journal of virology Result HIV N74D;P90A 5;13 9;17 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Likewise, VSV-G-pseudotyped full-length NL4.3GFP reporter virus bearing wild-type CA or N74D or P90A mutant CA showed similar titers in THP-1 cells. 2016 Journal of virology Result HIV N74D;P90A 88;96 92;100 Capsid;Capsid 82;108 84;110 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. MX2g1-1, as well as MX2g2-4 and Cntrl THP-1 cells, showed no substantial difference in infection by wild-type HIV-1 GFP reporter virus or CA mutants N74D or P90A in the absence of IFN-alpha prestimulation. 2016 Journal of virology Result HIV N74D;P90A 149;157 153;161 Capsid 138 140 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Overexpression of the type I IFN-induced protein MX2 blocks HIV-1 infection in a CA-sensitive manner, and CA amino acid substitutions N74D or P90A reduce the sensitivity of HIV-1 to ectopic MX2-mediated repression. 2016 Journal of virology Result HIV N74D;P90A 134;142 138;146 Capsid;Capsid 81;106 83;108 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Since we observed an increased sensitivity of the P90A CA mutant virus to IFN-alpha-induced MX2-independent antiviral effectors. 2016 Journal of virology Result HIV P90A 50 54 Capsid 55 57 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Surprisingly, when we tested VSV-G-pseudotyped HIV-1 GFP LV P90A in IFN-alpha-stimulated cells, we also observed an increased infectivity in the presence of Cs. 2016 Journal of virology Result HIV P90A 60 64 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. The A105T mutant was inhibited ~50-fold in THP-1 cells after IFN-alpha pretreatment, but like N74D, was not efficiently rescued from this block in cells lacking MX2. 2016 Journal of virology Result HIV A105T;N74D 4;94 9;98 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. The increased sensitivity of N74D or A105T viruses to IFN-alpha therefore cannot be explained by a lack of CPSF6 binding. 2016 Journal of virology Result HIV A105T;N74D 37;29 42;33 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. The infectivity of the P90A mutant virus was reduced by IFN-alpha to similar levels in all cell lines, suggesting that the P90A mutant phenocopied wild-type infections in the absence of CypA. 2016 Journal of virology Result HIV P90A;P90A 23;123 27;127 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Therefore, the increased IFN-alpha-induced block to N74D infection. 2016 Journal of virology Result HIV N74D 52 56 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Therefore, we decided to investigate whether CypA gene disruption would either increase the sensitivity of wild-type HIV-1 to IFN-alpha, phenocopying the P90A mutant, or would rescue wild type virus infectivity from the IFN-alpha-induced block, as observed with Cs treatment. 2016 Journal of virology Result HIV P90A 154 158 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. These data demonstrate that both HIV-1 CA N74D and P90A are hypersensitive to MX2-independent IFN-alpha-induced antiviral effectors. 2016 Journal of virology Result HIV N74D;P90A 42;51 46;55 Capsid 39 41 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. These results reveal that HIV-1 CA mutants N74D or P90A have increased sensitivity to IFN-alpha-induced blocks: this was unanticipated given their reduced sensitivity to MX2-mediated inhibition. 2016 Journal of virology Result HIV N74D;P90A 43;51 47;55 Capsid 32 34 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. These stable cell clones were pretreated with a serial dilution of IFN-alpha for 24 h and challenged with VSV-G-pseudotyped NL4.3GFP or the corresponding CA mutant virus NL4.3GFP P90A. 2016 Journal of virology Result HIV P90A 179 183 Capsid 154 156 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. To demonstrate formally that the increased sensitivity of HIV-1 CA mutants N74D or P90A to IFN-alpha-induced blocks is independent of MX2, we disrupted the MX2 gene in THP-1 cells using two independent CRISPR guide RNAs (MX2g1 and MX2g2). 2016 Journal of virology Result HIV N74D;P90A 75;83 79;87 Capsid 64 66 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. To test this hypothesis, we treated the myeloid cell line THP-1 with increasing amounts of IFN-alpha and challenged with equal doses of wild-type VSV-G-pseudotyped HIV-1 GFP lentiviral vector (LV) or viruses with the CA mutants N74D or P90A, as judged by their infectious titers on 293T cells, and determined the percentages of infected cells 2 days later. 2016 Journal of virology Result HIV N74D;P90A 228;236 232;240 Capsid 217 219 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. To test whether a lack in CPSF6 binding to CA could explain the enhanced sensitivity of HIV-1 CA N74D mutant to IFN-alpha-induced blocks, we studied HIV-1 CA A105T, another CPSF6-independent CA mutant. 2016 Journal of virology Result HIV A105T;N74D 158;97 163;101 Capsid;Capsid;Capsid;Capsid 43;94;155;191 45;96;157;193 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. We also observed a strong reduction in copy numbers of GFP reverse transcription products 24 h postinfection for both the wild type and the N74D mutant. 2016 Journal of virology Result HIV N74D 140 144 RT 59 80 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. We also observed increased sensitivity of N74D or A105T viruses to IFN-alpha-induced blocks in PMA-differentiated MX2 CRISPR/Cas9 THP-1 cells, as well as in MDMs, indicating that these blocks function independently of cell proliferation (data not shown). 2016 Journal of virology Result HIV A105T;N74D 50;42 55;46 Capsid 125 127 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. We confirmed that CA mutants N74D or P90A had modestly reduced infectivity in MDMs, as well as CD4+ T cells, compared to the wild type. 2016 Journal of virology Result HIV N74D;P90A 29;37 33;41 Capsid 18 20 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. We measured the infectivities of VSV-G-pseudotyped wild-type NL4.3GFP or the N74D mutant in THP-1 or CRISPR/Cas9 MX2g2-4 cells. 2016 Journal of virology Result HIV N74D 77 81 Capsid 108 110 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. We reasoned that N74D or P90A changes in HIV-1 CA might therefore reduce the sensitivity of HIV-1 to IFN-alpha-induced postentry blocks. 2016 Journal of virology Result HIV N74D;P90A 17;25 21;29 Capsid 47 49 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. We therefore inferred that the IFN-alpha-induced factors blocking HIV-1 CA mutants N74D or P90A might function independently of MX2. 2016 Journal of virology Result HIV N74D;P90A 83;91 87;95 Capsid 72 74 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. While for wild-type virus the 2-LTR circles were reduced ~9-fold in IFN-alpha-treated MX2g2-4 cells, the 2-LTR circles for N74D were blocked by almost 2 orders of magnitude. 2016 Journal of virology Result HIV N74D 123 127 LTR;LTR 32;107 35;110 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Wild-type and N74D or A105T viruses showed similar titers in the untreated parental, as well as CPSF6-depleted cell clones, and as expected, the N74D or A105T viruses showed increased sensitivity to IFN-alpha pretreatment in all cells. 2016 Journal of virology Result HIV A105T;A105T;N74D;N74D 22;153;14;145 27;158;18;149 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. In patients who had K103N, it was also the predominant variant within the viral population compared to the other mutations detected as minor variants only. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N 20 25 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. K103N and V106M were the most common mutations detected. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV V106M;K103N 10;0 15;5 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Mutations conferring low to intermediate NNRTI resistance included K101E in 7 of 26 (27%), A98G 5 of 26 (19%), L100V 4 of 26 (15%), V108I in 1 of 26 (3%) and F227L in 1 of 26 (3%) of patients. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV A98G;F227L;K101E;L100V;V108I 91;158;67;111;132 95;163;72;116;137 NNRTI 41 46 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Mutations conferring NRTI resistance included K70R in 2 of 26 (7%) patients and T69S which was detected in 1 of 26 (3%) patients. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K70R;T69S 46;80 50;84 NRTI 21 25 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. NNRTI resistance was detected in 17 of 26 (65%) patients, 2 (7%) patients had TAMs, and 3 (11%) patients had K65R. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 109 113 NNRTI 0 5 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Of all mutations conferring resistance to NNRTIs, the most common were those conferring high-level NNRTI resistance such as K103N in 8 of 26 (30%), V106M in 8 of 26 (30%), Y188C in 6 of 26 (23%), G190A in 4 of 26 (15%), Y181C in 3 of 26 (11%), and V106A in 3 of 26 (11%) patients. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K103N;V106A;V106M;Y181C;Y188C 196;124;248;148;220;172 201;129;253;153;225;177 NNRTI;NNRTI 42;99 48;104 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. One patient had both high-level NNRTI resistance and high-level resistance to TDF and 1 patient had both low to intermediate NNRTI resistance and K70R. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K70R 146 150 NNRTI;NNRTI 32;125 37;130 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Resistance to TDF (K65R) was found in 3/26 (11%) patients. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R 19 23 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. V90I which is associated with minimal, if any, detectable reduction in NNRTI susceptibility was found in 5 of 26 (19%) of patients. 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV V90I 0 4 NNRTI 71 76 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Algorithm assisted quantification of Nup358 relocalization confirmed that WT induced the cytoplasmic accumulation of Nup358 in both MDMs and HeLa cells, while virus lacking envelope, or harboring the N74D or P90A mutations, did not (Fig 4A and 4B). 2016 PLoS pathogens Result HIV N74D;P90A 200;208 204;212 Env 173 181 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. As previously reported, Nup358 depletion did not significantly influence nuclear import or infection by the N74D or P90A mutants. 2016 PLoS pathogens Result HIV N74D;P90A 108;116 112;120 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. As the N74D and P90A mutations are known to disrupt interactions with CPSF6 and Cyclophilin A (CypA), respectively, we determined the degree to which each factor was required for the interactions observed between HIV-1 viral cores and NUP358. 2016 PLoS pathogens Result HIV N74D;P90A 7;16 11;20 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Collectively, these data demonstrate that WT HIV-1nuclear entry is mediated by a Nup358, KIF5B dependent mechanism, and that nuclear entry of the N74D and P90A virus occur in a Nup358 and KIF5B independent manner. 2016 PLoS pathogens Result HIV N74D;P90A 146;155 150;159 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Collectively, these experiments demonstrate a specific association between WT viral cores and Nup358 in the cytoplasm of target cells that is dependent on the hydrophobic pocket disrupted by the N74D mutation and facilitated by the Cyp binding loop disrupted by the P90A mutation. 2016 PLoS pathogens Result HIV N74D;P90A 195;266 199;270 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. However, we did observe that infection with the P90A mutant induced more PLA puncta than the N74D mutant and other controls (Fig 6A and 6B), although the number of puncta induced by this mutant was consistently lower than WT in MDMs and HeLa cells (Fig 6B). 2016 PLoS pathogens Result HIV N74D;P90A 93;48 97;52 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. In contrast, Nup358 localization following infection with viral particles lacking envelope, or with the N74D or P90A mutants, appears less cytoplasmic and predominated around the nuclear envelope (Fig 4A). 2016 PLoS pathogens Result HIV N74D;P90A 104;112 108;116 Env;Env 82;187 90;195 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. In HIV-1 infected monocyte derived macrophages (MDMs), infectivity of the N74D and P90A mutants was attenuated (Fig 4A), while infectivity was not affected in HeLa cells (Fig 3C), as previously reported. 2016 PLoS pathogens Result HIV N74D;P90A 74;83 78;87 HIV infections 3 17 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Strikingly, we also observed that depletion of KIF5B did not affect nuclear import or infection by the P90A and N74D mutant viruses (Fig 3B and 3C). 2016 PLoS pathogens Result HIV N74D;P90A 112;103 116;107 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. The degree of colocalization between both the N74D and P90A mutants was similar to the degree of background colocalization between Nup358 and WT/DeltaEnv virus (Fig 5C) at both time points. 2016 PLoS pathogens Result HIV N74D;P90A 46;55 50;59 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. The N74D mutant also failed to induce PLA puncta following infection (Fig 6A and 6B), consistent with the lack of colocalization observed by immunofluorescence analysis (Fig 5A and 5B). 2016 PLoS pathogens Result HIV N74D 4 8 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Three hours following infection of MDMs, a higher percentage of WT viral particles were positive for Nup358 than WT/DeltaEnv, N74D or P90A (p<0.001) (Fig 5C). 2016 PLoS pathogens Result HIV N74D;P90A 126;134 130;138 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. We hypothesized that WT, but not the N74D or P90A mutants, might interact with Nup358 more efficiently during infection. 2016 PLoS pathogens Result HIV N74D;P90A 37;45 41;49 27333000 Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting. The following mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) drug resistance were detected: D67N, M184V, T215S, and K219Q. 2016 PloS one Result HIV D67N;K219Q;M184V;T215S 121;145;127;134 125;150;132;139 NRTI;NRTI 40;84 72;88 27333000 Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting. The M184V mutation was also detected by AS-PCR, and the protease-associated mutation L10I was also noted. 2016 PloS one Result HIV L10I;M184V 85;4 89;9 PR 56 64 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. The most frequent major mutations found among PHIV+ at enrollment were K103N (8/16, 50%) for NNRTIs; M184V (6/16, 38%), T215 (4/16, 25% ), M41L (3/16, 19%), and D67 (3/16, 19%) for NRTIs, and M46 (3/16, 19%), I54V (2/16, 13%) and V82A (2/16, 13%) for PIs. 2016 International journal of environmental research and public health Result HIV I54V;K103N;M184V;M41L;V82A 209;71;101;139;230 213;76;106;143;234 NNRTI;NRTI;PI 93;181;251 99;186;254 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). In N2-NP cells, although the WT virus replicated slowly when compared to its replication in T4 cells, it showed better replication than both DeltaVpr and the A30L mutant viruses, which was expected. 2016 Virology Result HIV A30L 158 162 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). Notably, even after N2-NP cells were treated with As2O3, resulting in an increase of the WT virus replication, the A30L mutant virus still replicated as poorly as the DeltaVpr virus, although its growth virus was detected on day 11. 2016 Virology Result HIV A30L 115 119 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). To further evaluate the importance of this residue in Vpr function, N2-NP and T4 cells were infected with WT, DeltaVpr, or the A30L mutant virus and viral replication was determined. 2016 Virology Result HIV A30L 127 131 Vpr 54 57 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). To understand how Vpr could increase Env expression, we introduced 6 mutations into these regions of Vpr, which include A30L, F34I, W54R, Q65R, and H71R. 2016 Virology Result HIV A30L;F34I;H71R;Q65R;W54R 120;126;148;138;132 124;130;152;142;136 Vpr;Vpr;Env 18;101;37 21;104;40 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). When the other viral protein expression was determined in MDDC, it was found that the A30L mutant virus expressed similarly low levels of Env as the DeltaVpr virus, whereas the other Vpr F34I, W54R, Q65R, and H71R mutant viruses expressed similar high levels of Env as the WT virus. 2016 Virology Result HIV A30L;F34I;H71R;Q65R;W54R 86;187;209;199;193 90;191;213;203;197 Vpr;Env;Env 183;138;262 186;141;265 27355415 Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia. Data on PI resistance mutations were available among 50 (68%) children, and included any major LPV mutation (L76V, V82A, V82S; 8%), >=6 LPV mutations (2%), any major darunavir (DRV) mutation (I84V, L76V; 2%), and any major ATV mutation (I84V, N88S; 4%) (Table 2). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV I84V;I84V;L76V;L76V;N88S;V82A;V82S 192;237;109;198;243;115;121 196;241;113;202;247;119;125 PI 8 10 27355415 Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia. NRTI mutations included >=1 TAM (40%), >=4 TAMs (10%), T215Y/F (23%), Q151M (4%), M184V (56%), K65R (2%). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R;M184V;Q151M;T215F;T215Y 95;82;70;55;55 99;87;75;62;62 NRTI 0 4 27355415 Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia. Of the 156 (56%) children who had available resistance testing at the time of first-line failure, mutations included M184V (82%), >=1 thymidine analog mutation (TAM; 64%), >=4 TAMs (18%), T215Y/F (43%), K65R (10%), >=1 NNRTI mutation (92%), Y181I/C (44%), G190A (33%), K103N/S (27%), and V108I (15%); 30 (19%) children had DUET weighted scores >=4 (Table 2). 2016 Journal of acquired immune deficiency syndromes (1999) Result HIV G190A;K103N;K103S;K65R;M184V;T215F;T215Y;V108I;Y181C;Y181I 256;269;269;203;117;188;188;288;241;241 261;276;276;207;122;195;195;293;248;248 NNRTI 219 224 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. A significant increase in TDR to any ARV drug was observed (p = 0.0068), which coincided with an increase in NNRTI TDR (p = 0.0008) and in particular of G190A mutation (p = 0.0038), while the increase in frequency for K103N was not significant (Fig 9). 2016 PloS one Result HIV G190A;K103N 153;218 158;223 NNRTI 109 114 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. A significant temporal increase in overall TDR was observed (p = 0.0044), which was associated with a significant increase in NNRTI TDR (p<0.0001) and frequency of K103N (p<0.0001) and G190A mutations (p = 0.02, Fig 7). 2016 PloS one Result HIV G190A;K103N 185;164 190;169 NNRTI 126 131 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. Additionally, a survey including 200 patients enrolled between 2009 and 2011 reported an overall TDR prevalence of 21.5%, with K103N and M184V being the most frequent TDR mutations. 2016 PloS one Result HIV K103N;M184V 127;137 132;142 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. Although a significant decrease in frequency of Y181C and G190A was observed (p<0.01), no significant trends were observed in NNRTI TDR. 2016 PloS one Result HIV G190A;Y181C 58;48 63;53 NNRTI 126 131 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. Although no significant change was observed in NRTI TDR prevalence, a significant decrease in the frequency of M41L (p = 0.04), T215Y (p = 0.008), and K70R (p = 0.046) mutations was observed (Fig 7). 2016 PloS one Result HIV K70R;M41L;T215Y 151;111;128 155;115;133 NRTI 47 51 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. Contrasting to other regions, no changes were observed in the frequency of K103N. 2016 PloS one Result HIV K103N 75 80 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. For this region, M184V (1.6%) and K103N (1.5%) were the most prevalent TDR mutations. 2016 PloS one Result HIV K103N;M184V 34;17 39;22 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. For this region, the most prevalent TDR mutations for the whole study period were K103N (2.0%), M184V (0.9%), M41L (0.8%), and D67N (0.6%). 2016 PloS one Result HIV D67N;K103N;M184V;M41L 127;82;96;110 131;87;101;114 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. The most frequent DR mutations in the region were M41L (1.2%) and K103N (2.2%). 2016 PloS one Result HIV K103N;M41L 66;50 71;54 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. The most frequent TDR mutations for the whole country for the entire study period were M41L (1.4%), and K103N (2.4%). 2016 PloS one Result HIV K103N;M41L 104;87 109;91 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. The most prevalent DR mutations included M41L (1.1%), M184V (2.0%) for NRTI, and K103N (2.2%), Y181C (1.4%) and G190A (1.2%) for NNRTI (Fig 4). 2016 PloS one Result HIV G190A;K103N;M184V;M41L;Y181C 112;81;54;41;95 117;86;59;45;100 NNRTI;NRTI 129;71 134;75 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. The overall decrease in NRTI TDR was associated with a significant decrease in the frequency of M184V (p = 0.03) and the thymidine analog mutations (TAMs) K70R (p<0.0001) and T215Y (p = 0.007) (Fig 2). 2016 PloS one Result HIV K70R;M184V;T215Y 153;96;175 159;101;180 NRTI 24 28 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. The overall increase in NNRTI TDR was associated with a significant increase in the frequency of K101E (p = 0.03), K103N (p<0.0001), and G190A (p = 0.008; Fig 2). 2016 PloS one Result HIV G190A;K101E;K103N 137;97;115 142;102;120 NNRTI 24 29 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. This decreasing trend was associated with reductions in frequency of several DR mutations including D67N, K70R, M184V, L210W, T215F, T215Y, and K219E (p<0.05; Fig 5). 2016 PloS one Result HIV D67N;K219E;K70R;L210W;M184V;T215F;T215Y 100;144;106;119;112;126;133 104;149;110;124;117;131;138 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. This increase in TDR was also associated with significant increase in the prevalence of several DR mutations, mainly M184V for NRTI; and K103N, Y181C and G190A for NNRTI. 2016 PloS one Result HIV G190A;K103N;M184V;Y181C 154;137;117;144 159;142;122;149 NNRTI;NRTI 164;127 169;131 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. This observation may be explained by a trend of increasing frequency of K103N (p = 0.0558) and the appearance of viruses with the Y181C, G190A, and P225H mutations in the 2006-2015 period at low frequency (Fig 6). 2016 PloS one Result HIV G190A;K103N;P225H;Y181C 137;72;148;130 142;77;153;135 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Abasic substrates differentially affect the 3'-P activity of the G140S-Q148H (SH) IN mutant and RAL resistance. 2016 Nucleic acids research Result HIV G140S;Q148H 65;71 70;76 IN 82 84 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Among the five compounds shown in Figure 6, those with the highest selectivity for ST over 3'-P were also the most susceptible to the SH and N155H mutants (Figures 6 and Supplementary Figure S3). 2016 Nucleic acids research Result HIV N155H 141 146 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Earlier studies showed that the RAL-resistant mutant Q148H and the double mutant G140S-Q148H (SH mutant), in which the amino acids that are changed flank the flexible loop of IN, both exhibit an impaired catalytic activity and have a kinetic defect. 2016 Nucleic acids research Result HIV G140S;Q148H;Q148H 81;53;87 86;58;92 IN 175 177 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Next, the 3'-P and ST catalytic activities of the Q146A, E, T and K IN mutants were tested using the full-length canonical duplex 21 bp substrate (Figure 5A). 2016 Nucleic acids research Result HIV Q146A 50 55 IN 68 70 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. No correlation was found for the Y143R mutant (Supplementary Figure S4). 2016 Nucleic acids research Result HIV Y143R 33 38 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. The catalytic activities of all of the mutants were reduced, except Q146K which had 3'-P and ST levels similar to WT IN (Figure 5A and B). 2016 Nucleic acids research Result HIV Q146K 68 73 IN 117 119 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. The fact that the Q146K mutant had full catalytic activity could be explained by the fact that the flexible amino side chain of the lysine residue can probably still interact with the T-1 and C+1 of the non-cleaved strand (Figure 4). 2016 Nucleic acids research Result HIV Q146K 18 23 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. The lack of correlation for the Y143R mutant is consistent with the specific interaction of this residue with RAL but not with the other INSTIs. 2016 Nucleic acids research Result HIV Y143R 32 37 INSTI 137 143 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. The most deleterious mutation for 3'-P activity was Q146A (Figure 5A). 2016 Nucleic acids research Result HIV Q146A 52 57 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. They also suggest that 3'-P inhibition is an indicator of the ability of compounds to retain efficacy against the SH (and N155H) mutants. 2016 Nucleic acids research Result HIV N155H 122 127 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. To investigate the role of residue Q146, we generated four mutants at this position: Q146A, Q146E, Q146T and Q146K. 2016 Nucleic acids research Result HIV Q146A;Q146E;Q146K;Q146T 85;92;109;99 90;97;114;104 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Together, these results reveal a significant correlation between the relative activity of a drug as a 3'-P inhibitor and its ability to overcome resistance to the SH mutant, and to a lesser extent, to the N155H mutant. 2016 Nucleic acids research Result HIV N155H 205 210 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. We also tested the ST selectivity and resistance index relationships for the N155H mutant. 2016 Nucleic acids research Result HIV N155H 77 82 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. All mutations identified in CRF37_cpx, CRF22_01A1, CRF18_cpx, and subtype-D isolates were present in 100% of samples analyzed (Table 2), and mutations identified in the CRF02_AG, CRF11_cpx, CRF13_cpx, CRF01_AE, and subtype-G isolates were present in 40%-100% of samples analyzed (Table 2), with the exception of K29T mutation in subtype-G cysteine-rich region that was present in only 33.3% of samples analyzed (Figure 3 and Table 2). 2016 Viruses Result HIV K29T 312 316 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. All subtype-G samples also showed N24K mutation, and 42% of CRF02_AG samples had S23N substitution (Figure 4). 2016 Viruses Result HIV N24K;S23N 34;81 38;85 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Compared to consensus sequences, C residues in the cysteine-rich region were conserved in 93% of samples analyzed; only three CRF02_AG isolates showed mutations at C31 (C31S/A/F), and one CRF18_cpx isolate showed a C31S mutation (Figure 4). 2016 Viruses Result HIV C31A;C31F;C31S;C31S 169;169;169;215 177;177;177;219 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Compared to consensus sequences, no major mutations were observed in the Tat N-terminal region of Cameroon isolates except the P3L substitution in 63% of CRF02_AG isolates (Figure 4). 2016 Viruses Result HIV P3L 127 130 Tat 73 76 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Mutations identified in the Core region included I39T in CRF13_cpx (Figure 3D); K40N in CRF22_01A1 (Figure 3F) and Y47H in CRF18_cpx isolates (Figure 3G). 2016 Viruses Result HIV I39T;K40N;Y47H 49;80;115 53;84;119 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Mutations identified in the Tat cysteine-rich region included N29K and N36I in CRF02_AG and CRF11_cpx viral isolates, respectively (Figure 3A,B); N23T, N24K, and K29T in subtype-G isolates (Figure 3C); N23T and T24K in CRF13_cpx (Figure 3D); K24S, Y26H, and K29H in subtype-D (Figure 3E); N24K and F26W in CRF22_01A1 (Figure 3F); K24Q, C31S, and P35Q in CRF18_cpx (Figure 3G); and N23S and K29R in CRF01_AE isolates (Figure 3H). 2016 Viruses Result HIV C31S;F26W;K24Q;K24S;K29H;K29R;K29T;N23S;N23T;N23T;N24K;N24K;N29K;N36I;P35Q;T24K;Y26H 336;298;330;242;258;390;162;381;146;202;152;289;62;71;346;211;248 340;302;334;246;262;394;166;385;150;206;156;293;66;75;350;215;252 Tat 28 31 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Mutations in the Basic (TAR-binding) region included A57T in CRF11_cpx (Figure 3B); R52W in CRF13_cpx (Figure 3D); K53R and R54H in CRF22_01A1 (Figure 3F); T57A in CRF18_cpx (Figure 3G), K53R in CRF01_AE (Figure 3H); and R57G in subtype-D isolates (Figure 3E). 2016 Viruses Result HIV A57T;K53R;K53R;R52W;R54H;R57G;T57A 53;115;187;84;124;221;156 57;119;191;88;128;225;160 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Mutations in the glutamine (Q)-rich region included S70P in CRF11_cpx (Figure 3B); P58T, S59P, S62N, Q63K, and P70Q in subtype-G (Figure 3C); A58T, S59T, H60P, and L68P in CRF13_cpx (Figure 3D); P59A, T61S, and H65N in CRF37_cpx (Figure 3I); H65N, V67D, P68S, and K71N in subtype-D (Figure 3E); Q60H and P68L in CRF22_01A1 (Figure 3F); P59S, Y60H, and D61S in CRF18_cpx (Figure 3G); E63K, P70S, and K71Q in CRF01_AE isolates (Figure 3H). 2016 Viruses Result HIV A58T;D61S;E63K;H60P;H65N;H65N;K71N;K71Q;L68P;P58T;P59A;P59S;P68L;P68S;P70Q;P70S;Q60H;Q63K;S59P;S59T;S62N;S70P;T61S;V67D;Y60H 142;352;383;154;211;242;264;399;164;83;195;336;304;254;111;389;295;101;89;148;95;52;201;248;342 146;356;387;158;215;246;268;403;168;87;199;340;308;258;115;393;299;105;93;152;99;56;205;252;346 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Several CRF02_AG samples showed mutations of asparagine (N) into lysine (K) in the cysteine-rich and Core regions, including N24K, N29K, and N40K in 44%, 58%, and 30% of samples, respectively (Figure 4). 2016 Viruses Result HIV N24K;N29K;N40K 125;131;141 129;135;145 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. BiFC-INV165A containing a V165A substitution, which fails to interact with LEDGF/p75 and Venus proteins, were applied as a negative control. 2016 Journal of virological methods Result HIV V165A 26 31 IN 5 7 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. However, significant differences in the NCINI-3-induced increases of AUC ratios between BiFC-INE11K and BiFC-INF181T were not found at such high concentrations. 2016 Journal of virological methods Result HIV E11K;F181T 95;111 99;116 IN;IN 93;109 95;111 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. In line with the interaction profile of purified non-tagged IN multimers with LEDGF/p75, Venus-IN and BiFC-INWT were capable of interacting with endogenous LEDGF/p75, in contrast, BiFC-INV165A showed a severe decreased interaction with LEDGF/p75, and Venus had no interaction of LEDGF/p75. 2016 Journal of virological methods Result HIV V165A 187 192 IN;IN;IN 60;95;185 62;97;187 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. Indeed, BiFC-INE11K and BiFC-INK186E proteins efficiently expressed in the cells, resulted in significant loss of AUC ratios (0.60 and 0.73, respectively) compared to that in BiFC-INWT. 2016 Journal of virological methods Result HIV E11K;K186E 15;31 19;36 IN;IN 13;29 15;31 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. Interestingly, it has been reported that the E11K and K186E substitutions are located within the putative dimer-dimer interface, between two identical NTD-CCD molecules, shift the equilibrium state of IN multimers from tetramers to dimers and/or monomers, and the mixture of purified INE11K and INK186E proteins are restored to tetramer subunits as INWT proteins. 2016 Journal of virological methods Result HIV E11K;K186E 45;54 49;59 IN;IN;IN 201;284;295 203;286;297 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. Moreover, in order to investigate whether we can evaluate adequately IN multimerization by using the BiFC-IN system containing such inherent VN-VC interaction, we produced pBiFC-INs containing E11K and/or K186E substitutions which are associated with IN multimerization/tetramerization. 2016 Journal of virological methods Result HIV E11K;K186E 193;205 197;210 IN;IN;IN;IN 69;106;178;251 71;108;181;253 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. On the other hand, as previously reported by Bojja et al., an F181T substitution located at the conserved hydrophobic residues on CCD-CCD interface, inhibited IN dimers based on CCD dimer type in the absence of viral DNA, and shifted the equilibrium state of IN multimers to a unique dimer type termed a "reaching dimer", which is thought to lose IN's interaction with NCINIs. 2016 Journal of virological methods Result HIV F181T 62 67 IN;IN;IN 159;259;347 161;261;349 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. On the other hand, in line with the previous report, the AUC ratio of BiFC-INE11K+K186E containing E11K plus K186E substitutions switched the AAs at E11 and K186 positions each other, which are located within the putative dimer-dimer interface, and are restored at 0.93 by the same level observed in BiFC-INWT. 2016 Journal of virological methods Result HIV E11K;E11K;K186E;K186E 99;77;82;109 103;81;87;114 IN 75 77 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. The AUC ratio of BiFC-IND116A containing D116A substitution located at the catalytic active site of IN used as a positive control, was measured at 1.07 similar to that of BiFC-INWT. 2016 Journal of virological methods Result HIV D116A 41 46 IN;IN 22;100 24;102 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. The AUC ratios of BiFC-INE11K slightly increased at concentrations of 1 muM and above of NCINI-3, and those of BiFC-IN F181T that does not have the binding pocket of NCINIs also slightly increased at high concentrations of NCINI-3, 5 and 10 muM. 2016 Journal of virological methods Result HIV F181T 119 124 IN;IN 23;116 25;118 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. The E11K substitution known to block IN tetramerization shifts the equilibrium state of IN multimers from tetramers to dimers based on CCD dimer type which can interact with NCINIs. 2016 Journal of virological methods Result HIV E11K 4 8 IN;IN 37;88 39;90 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. In isolation, these mutations are not reported to affect susceptibility to integrase inhibitors with the exception of E157Q, which confers low-level resistance to raltegravir and elvitegravir. 2017 HIV medicine Result HIV E157Q 118 123 IN 75 84 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. K65R was only detected in 10 (0.06%) individuals tested between 2010 and 2013. 2017 HIV medicine Result HIV K65R 0 4 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. Six individuals had minor or accessory mutations: one had L74M, two had V151I and three had E157Q. 2017 HIV medicine Result HIV E157Q;L74M;V151I 92;58;72 97;62;77 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. The most frequently detected mutations were T215 revertants (not F/Y) (268; 1.6%) and other TAMs [M41L (141; 0.9%) and K219Q/N (104; 0.6%)] conferring resistance to the NRTI drug class; K103N (354; 2.2%) and Y181C (66; 0.4%) conferring resistance to the NNRTI drug class, and L90M (111; 0.7%) and M46L (48; 0.3%) conferring resistance to the PI drug class. 2017 HIV medicine Result HIV K103N;K219N;K219Q;L90M;M41L;M46L;Y181C 186;119;119;276;98;297;208 191;126;126;280;102;301;213 NNRTI;NRTI;PI 254;169;342 259;173;344 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. As expected, A77P and L189P amino acid changes inhibited the proteolytic processing at these sites, as we have observed a decrease in the product band intensities or disappearance of the fragments related to these modified cleavage sites. 2016 FEBS open bio Result HIV A77P;L189P 13;22 17;27 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Based on these results, the introduced mutations (with the exception of A77P) leading to changes in the secondary structural organization (Table 1) did not affect the CypA-binding ability of CA protein. 2016 FEBS open bio Result HIV A77P 72 76 Capsid 191 193 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Based on these results, we can conclude that the W23A, A77P, and L189I mutant proteins are more sensitive to trypsin, compared to the wild-type capsid protein. 2016 FEBS open bio Result HIV A77P;L189I;W23A 55;65;49 59;70;53 Capsid 144 150 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Besides these mutations, we also studied the Trp23Ala mutant. 2016 FEBS open bio Result HIV W23A 45 53 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. However, in case of the W23A, A77P, and L189I mutants the percentage of the uncleaved CA showed significant reduction. 2016 FEBS open bio Result HIV A77P;L189I;W23A 30;40;24 34;45;28 Capsid 86 88 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. However, the overall processing of the L189F CA was reduced, and A78V CA did not show significant alteration in its proteolytic susceptibility compared to that of the wild-type. 2016 FEBS open bio Result HIV A78V;L189F 65;39 69;44 Capsid;Capsid 45;70 47;72 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. However, while the introduction of W23A mutation was predicted to be neutral from the viewpoint of the conformation of helix I, it was previously published that this residue is buried in the N-terminal domain and contributes to the formation of the hydrophobic core 58. 2016 FEBS open bio Result HIV W23A 35 39 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. In case of the CA proteins bearing the A78V, L189F, or L189P mutations the efficiency of proteolytic digestion was found to be similar to that of the wild-type, no significant difference was observed. 2016 FEBS open bio Result HIV A78V;L189F;L189P 39;45;55 43;50;60 Capsid 15 17 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. In summary, based on the results of CD, the secondary structure of the A78V, L189F, and L189I mutants show only slight differences and closely resemble that of the wild-type (Table 1). 2016 FEBS open bio Result HIV A78V;L189F;L189I 71;77;88 75;82;93 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Mutant capsid proteins W23A, A77P, and L189I are more sensitive to tryptic digestion, while A78V, L189F, and L189P mutants showed similar tryptic susceptibility to that of the wild-type CA. 2016 FEBS open bio Result HIV A77P;A78V;L189F;L189I;L189P;W23A 29;92;98;39;109;23 33;96;103;44;114;27 Capsid;Capsid 7;186 13;188 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. On the other hand, the W23A mutation resulted in the accelerated proteolytic cleavage of the protein, in good agreement with previously published results 2. 2016 FEBS open bio Result HIV W23A 23 27 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. On the other hand, W23A and A77P mutants show more pronounced changes in the percentage of secondary structural elements, the structure of L189P mutant capsid proteins highly deviated from that of the highly alpha-helical wild-type (Table 1). 2016 FEBS open bio Result HIV A77P;L189P;W23A 28;139;19 32;144;23 Capsid 152 158 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Predicted effects of A78V, L189F, and L189I mutations corresponded well with the experimentally determined effects, and while the distribution of secondary structural elements in L189I mutant closely resembles that of the wild-type CA, the A78V and the L189F mutants show only minor differences compared to the wild-type protein. 2016 FEBS open bio Result HIV A78V;A78V;L189F;L189F;L189I;L189I 21;240;27;253;38;179 25;244;32;258;43;184 Capsid 232 234 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Remarkable alterations predicted for the structures of A77P and L189P mutant capsid proteins were confirmed by CD measurements. 2016 FEBS open bio Result HIV A77P;L189P 55;64 59;69 Capsid 77 83 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Secondary structure prediction did not predict changes for W23A mutation, furthermore, SDM server predicted only slightly destabilizing effect for this mutation, as well. 2016 FEBS open bio Result HIV W23A 59 63 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Surprisingly, L189I mutation did not prevent processing at this site, although P1 Ile has not been found in HIV-1 cleavage sites. 2016 FEBS open bio Result HIV L189I 14 19 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The amount of CypA associated with the W23A, A78V, L189F, L189I, and L189P mutants did not change significantly, while A77P mutant showed a highly reduced CypA binding ability compared to that of the wild-type CA protein. 2016 FEBS open bio Result HIV A77P;A78V;L189F;L189I;L189P;W23A 119;45;51;58;69;39 123;49;56;63;74;43 Capsid 210 212 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The highest values were predicted for the A77P (-2.27 kcal mol-1) and L189P (-4.85 kcal mol-1) mutants, which suggested that these mutations have a highly destabilizing effect on the protein structure and may potentially cause protein malfunction. 2016 FEBS open bio Result HIV A77P;L189P 42;70 46;75 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The L189I mutation was predicted to be neutral (-0.37 kcal mol-1), while A78V and L189F mutations were predicted to be slightly destabilizing (-1.57 and -0.73 kcal mol-1, respectively) and cause only a slight deviation of the secondary structural organization. 2016 FEBS open bio Result HIV A78V;L189F;L189I 73;82;4 77;87;9 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The modified cleavage sites became more susceptible to proteolytic cleavage in the case of A78V and L189F mutants, as indicated by the increased amount of the related fragments (78-231 and 1-189, respectively). 2016 FEBS open bio Result HIV A78V;L189F 91;100 95;105 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The spectra of A78V and L189F mutants showed similar features to that of the wild-type, indicating that these proteins have the same distribution of secondary structural elements (Table 1). 2016 FEBS open bio Result HIV A78V;L189F 15;24 19;29 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The spectra of the W23A, A77P, and L189P mutants exhibited several different features compared to that of the wild-type, such as highly reduced positive and negative ellipticity and altered crossover points of the curves, indicating the variable distribution of secondary structures. 2016 FEBS open bio Result HIV A77P;L189P;W23A 25;35;19 29;40;23 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The spectrum of L189I mutant also exhibited similar features with a higher maximum at 191 nm, suggesting that its structure only slightly differs from that of the wild-type protein in its alpha-helix ratio. 2016 FEBS open bio Result HIV L189I 16 21 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Therefore, we expected that W23A mutation would alter both the secondary and tertiary structure of CA protein, due to its critical role in stabilization of the protein structure. 2016 FEBS open bio Result HIV W23A 28 32 Capsid 99 101 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. To define the effects of proteolytic cleavage site mutations on the in vitro CA processing, we prepared mutant capsid proteins in which the P1 (A77P, L189F, L189I, and L189P mutants) or the P1' (W23A and A78V mutants) amino acids of the cleavage sites were replaced. 2016 FEBS open bio Result HIV A77P;A78V;L189F;L189I;L189P;W23A 144;204;150;157;168;195 148;208;155;162;173;200 Capsid;Capsid 111;77 117;79 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. 4, when the baseline infectivity of F56C/L63P was matched to F56C and the parental virus (panel A), the double mutant exhibited IDV resistance similar to that observed for F56C alone (panel B) indicating that the L63P polymorphism made no detectable contribution. 2016 Retrovirology Result HIV F56C;F56C;F56C;L63P;L63P 36;61;172;41;213 40;65;176;45;217 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Additionally, the p6*-PR-HAb released from the F56C mutant precursor appeared to maintain a high level of detection over a wider IDV range than that released from the WT control. 2016 Retrovirology Result HIV F56C 47 51 Gag;PR 18;22 20;24 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. An examination of the HIV-1 sequences obtained from the other participants with variants encoding the S40A polymorphism revealed that the substitution of A for S40 was the result of identical mutations. 2016 Retrovirology Result HIV S40A 102 106 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Another interesting observation was that the two F56C-containing constructs released more PR-V5 products than the WT and F56 V controls and demonstrated consistently high levels of trans processing products even at micromolar concentrations of IDV. 2016 Retrovirology Result HIV F56C;F56V 49;121 53;126 PR 90 92 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. As noted above, compared to WT, S40A/F56C tested over a concentration range of 0.01-10 muM exhibited no difference in resistance at concentrations above 0.01 muM. 2016 Retrovirology Result HIV F56C;S40A 37;32 41;36 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. As noted above, the S40F mutation does not alter the sequence of the overlapping pol frame while the S40A change causes a radical change at the N-terminal PR cleavage site encoded in the overlapping pol frame, the substitution of C for F56. 2016 Retrovirology Result HIV S40A;S40F 101;20 105;24 Pol;Pol;PR 81;199;155 84;202;157 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. As previously reported by ourselves and others, the S40F polymorphism does not inhibit virus budding but affects several other aspects of viral replication, including Gag processing, maturation and infectivity. 2016 Retrovirology Result HIV S40F 52 56 Gag 167 170 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Collectively, the F56C mutation exerted multifaceted effects including (1) decreased production of free mature PR due to suboptimal substrate sequence, (2) release of an extended PR form (p6*-PR-HAa) that is fairly stable over a wide range of IDV. 2016 Retrovirology Result HIV F56C 18 22 Gag;PR;PR;PR 188;111;179;192 190;113;181;194 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. For these studies, we combined the most radical of these substitutions, L63P, with the S40A/F56C mutation forming F56C/L63P. 2016 Retrovirology Result HIV F56C;F56C;L63P;L63P;S40A 92;114;72;119;87 96;118;76;123;91 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Furthermore, the p6*-PR-HAb enzyme in the context of F56C content was more effective at trans processing than those made by the WT or F56 V controls while being resistant to IDV suppression. 2016 Retrovirology Result HIV F56C;F56V 53;134 57;139 Gag;PR 17;21 19;23 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Highlighted in blue are the sequences isolated from participant #36; highlighted in red are the sequences isolated from additional WIHS participants with HIV sequences with the S40A polymorphism. 2016 Retrovirology Result HIV S40A 177 181 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. L63P is a common polymorphism, however, its frequency was found to increase in PR inhibitor-treated patients. 2016 Retrovirology Result HIV L63P 0 4 PR 79 81 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Moreover, covariance analysis indicated that F56C/L63P is a covarying pair existing at a low percentage in the drug-naive population in LANL. 2016 Retrovirology Result HIV F56C;L63P 45;50 49;54 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Mutation of S40 to Ala (S40A) has little apparent effect on virus budding, maturation, or infectivity. 2016 Retrovirology Result HIV S40A 24 28 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Remarkably, the L domain-2 mutation S40A was observed more frequently in the WIHS participants than the S40F change. 2016 Retrovirology Result HIV S40A;S40F 36;104 40;108 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. S40A was identified in 27/27 single genome variants amplified from genital tract and plasma specimens taken at a single visit and in 5 unrelated participants whereas S40F was detected in 2/28 variants in only 1 participant. 2016 Retrovirology Result HIV S40F;S40A 166;0 170;4 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Since the substitution of Ala alters the PR, we can conclude that the altered PR can cleave CA-SP1, permitting virus maturation, and is responsible for the maintaining of the infectivity in the S40A variant. 2016 Retrovirology Result HIV S40A 194 198 SP1;Capsid;PR;PR 95;92;41;78 98;94;43;80 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Strikingly, L63P and other L63 substitutions were apparent in every variant bearing the S40A mutation. 2016 Retrovirology Result HIV L63P;S40A 12;88 16;92 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Taken together, the results demonstrate that the F56C mutation interfered with proximal site processing leading to reduced production of free mature PR-HA. 2016 Retrovirology Result HIV F56C 49 53 PR 149 151 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The D25N precursor is auto-processing defective due to the catalytic site mutation (panel 5C, lane 6). 2016 Retrovirology Result HIV D25N 4 8 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The F56C mutation interferes with mature PR release from a model precursor. 2016 Retrovirology Result HIV F56C 4 8 PR 41 43 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The F56C mutation reduced proximal site processing as indicated by reduced amounts of the proximal processing products, L-MBP-Flag-p6* and PR-HA, compared to the WT control (panel 5C, lane 3). 2016 Retrovirology Result HIV F56C 4 8 Gag;PR 131;139 133;141 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The F56C mutation showed several changes compared to the WT control. 2016 Retrovirology Result HIV F56C 4 8 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The F56V control was unable to release any mature PR and only produced p6*-PR-HAa and p6*-PR-HAb enzymes that demonstrated low level of trans processing. 2016 Retrovirology Result HIV F56V 4 8 Gag;Gag;PR;PR;PR 71;86;50;75;90 73;88;52;77;92 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The results indicate that the S40A polymorphism increased resistance to IDV, albeit at low drug concentration. 2016 Retrovirology Result HIV S40A 30 34 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The S40A and S40F mutations were engineered into an HIV genome (pNL4-3) and the viral particles produced by transfected cells were examined. 2016 Retrovirology Result HIV S40A;S40F 4;13 8;17 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The S40A mutation in Gag alters the amino acid sequence at the p6*-PR cleavage site in the overlapping pol frame. 2016 Retrovirology Result HIV S40A 4 8 Pol;Gag;Gag;PR 103;21;63;67 106;24;65;69 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The S40A mutation in NL4-3 alters PI sensitivity. 2016 Retrovirology Result HIV S40A 4 8 PI 34 36 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The substrate (Myc-M2-PRD25N-V5) is a mini-precursor derivative carrying D25N mutation making it catalytically inactive, however, it has the WT proximal PR cleavage site and thus can be processed by a trans acting enzyme to release a PR(D25N)-V5 product. 2016 Retrovirology Result HIV D25N;D25N 73;237 77;241 PR;PR;PR 22;153;234 24;155;236 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. These results support the supposition that the F56C mutation altered precursor autoprocessing leading to release of products with distinct enzymatic activities in the presence or absence of IDV. 2016 Retrovirology Result HIV F56C 47 51 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. This increased resistance most likely reflects an impact on PR resulting from the F56C mutation at its N-terminal processing site. 2016 Retrovirology Result HIV F56C 82 86 PR 60 62 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. This strongly suggests that the Gag p6 S40A/Pol p6*-PR F56C mutation was selected and maintained in the quasispecies in the infected participants, possibly because these changes conferred a replicative advantage in the presence of PR inhibitors. 2016 Retrovirology Result HIV F56C 55 59 Pol;Gag;Gag;Gag;PR;PR 44;32;36;48;52;231 47;35;38;50;54;233 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Thus, the F56C mutation altered the detection profile of the p6*-PR-HAa product. 2016 Retrovirology Result HIV F56C 10 14 Gag;PR 61;65 63;67 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. To begin to understand the nature of the potential replicative advantage conferred by the S40A [gag frame]/F56C [pol frame] polymorphism, the replication of the S40A mutant was examined in the absence and presence of PI. 2016 Retrovirology Result HIV F56C;S40A;S40A 107;90;161 111;94;165 Pol;Gag;PI 113;96;217 116;99;219 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. To investigate the supposition that the Gag p6 S40A/Pol p6*-PR F56C mutation impacted PR in a manner that changed IDV susceptibility, we determined the effect of the F56C mutation on precursor autoprocessing, using a model precursor engineered to express in transfected mammalian cells. 2016 Retrovirology Result HIV F56C;F56C 63;166 67;170 Pol;Gag;Gag;Gag;PR;PR 52;40;44;56;60;86 55;43;46;58;62;88 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. To test the supposition that the F56C mutation influences with PR autoprocessing in the presence of the PR inhibitor, we examined autoprocessing products in response to IDV treatment. 2016 Retrovirology Result HIV F56C 33 37 PR;PR 63;104 65;106 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Trans cleavage by F56C-related PR products. 2016 Retrovirology Result HIV F56C 18 22 PR 31 33 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. We also engineered and tested F56 V and F56I precursors in parallel as these two mutations are expected to completely block proximal processing: a previous sequence analysis revealed the absence of beta-branched amino acids at the P1 position of PR substrates. 2016 Retrovirology Result HIV F56I;F56V 40;30 44;35 PR 246 248 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. We then reasoned that perhaps replicative advantage is conferred when the S40A is combined with other drug resistance mutations in PR. 2016 Retrovirology Result HIV S40A 74 78 PR 131 133 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. When the baseline infectivity of S40A and the parental virus was matched (panel A), the the S40A mutant was found to exhibit threefold greater resistance to 0.01 muM IDV compared to the WT (panel B). 2016 Retrovirology Result HIV S40A;S40A 33;92 37;96 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Although GFP+ expression in target cells remained negative up to >100 days in culture, viral RNA was successfully extracted from the supernatant and the respective L188F and T186S mutations, confirmed by sequencing. 2016 Retrovirology Result HIV L188F;T186S 164;174 169;179 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. For example, T190I shows a modest compensatory effect in combination with L188F in NL4-3, but not in SK-254 or SK-254(M). 2016 Retrovirology Result HIV L188F;T190I 74;13 79;18 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. However, the variable ability of variants at 190-Thr to compensate successfully for the fitness cost of the T186S escape mutant according to viral backbone (NL4-3, SK-254 or SK-254(M)) is not explained by these models, with the majority of the differences between these viruses located within the carboxy-terminal domain (Additional file 2: Table S2). 2016 Retrovirology Result HIV T186S 108 113 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Impact of L188F on viral replicative capacity. 2016 Retrovirology Result HIV L188F 10 15 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. In order to better understand why the HLA-B*81:01-driven escape mutants L188F and T186S have such a marked impact on VRC, we analyzed these mutants using previously solved crystal structures of the capsid protein. 2016 Retrovirology Result HIV L188F;T186S 72;82 77;87 Capsid 198 204 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. In relation to T186S, T190A and T190I are compensatory in the setting of NL4-3, but only T190I in the context of SK254 and only T190A in the context of SK254(M). 2016 Retrovirology Result HIV T186S;T190A;T190A;T190I;T190I 15;22;128;32;89 20;27;133;37;94 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Irrespective of the backbone, any viruses encoding L188F or T186S were incapable of replicating at a sufficient level in vitro to measure VRC. 2016 Retrovirology Result HIV L188F;T186S 51;60 56;65 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Modeling of the L188F substitution would indicate that all but one of these 7 van der Waals interactions are disrupted. 2016 Retrovirology Result HIV L188F 16 21 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Of note, however, the entire Gag-Pro sequence taken from GD to form a chimeric virus with NL4-3 replicated as well as SK-254(M) WT, despite containing the L188F variant. 2016 Retrovirology Result HIV L188F 155 160 Gag 29 32 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Previous studies have demonstrated that the most common escape variants within the HLA-B*81:01-TL9 epitope, T186S and Q182S/T186S (Table 1), can have a substantial impact on viral replicative capacity (VRC). 2016 Retrovirology Result HIV Q182S;T186S;T186S 118;108;124 123;113;129 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Rare mutation Gag-L188F within HLA-B*81:01-TL9 epitope shared by transmission trio. 2016 Retrovirology Result HIV L188F 18 23 Gag 14 17 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Similarly, modeling would suggest that the consequence of the T186S escape mutant would be to abrogate 3 of 4 van der Waals interactions between 186-Thr on helix-3 and 152-Leu and 147-Ile on helix-1. 2016 Retrovirology Result HIV T186S 62 67 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Structural analysis indicates likely mechanism of L188F and T186S impact on VRC. 2016 Retrovirology Result HIV L188F;T186S 50;60 55;65 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. The destabilizing impact of this would, however, be largely mitigated by the compensatory T190I mutation, in providing 3 new van der Waals interactions between 190-Ile and 152-Leu. 2016 Retrovirology Result HIV T190I 90 95 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. The virus in all family members GM, D2 and GD expressed the mutation Gag-L188F (Table 1). 2016 Retrovirology Result HIV L188F 73 78 Gag 69 72 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. These data are consistent either with L188F being an escape mutant driven by the HLA-B*81:01-TL9 response in GM and transmitted to both GD and D2; or being selected independently in each of the three family members, all of whom express HLA-B*81:01 (Additional file 1: Table S1). 2016 Retrovirology Result HIV L188F 38 43 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. This indicates that one or more of the additional variants within the Gag-Pro sequence of the GD were capable of compensating for L188F. 2016 Retrovirology Result HIV L188F 130 135 Gag 70 73 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. To consider the impact of the L188F escape mutant, the contacts between 188-Leu and neighboring residues 184L, 198M, 201L and 266I were identified, these forming 7 van der Waals interactions, in addition to the hydrogen bond between the backbone amine group at residue 188 and the backbone carbonyl group at residue 184. 2016 Retrovirology Result HIV L188F 30 35 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. To investigate the possibility that this rare L188F mutant might similarly affect VRC, thereby contributing to slow progression observed in subjects GD and D2, this variant was generated by site-directed mutagenesis and the replicative capacity compared with the more common and well-described HLA-B*81:01-associated TL9 escape mutants, T186S, the combination of T186S/Q182S, and the putative compensatory mutants T190A and T190I (33; Table 1). 2016 Retrovirology Result HIV L188F;Q182S;T186S;T186S;T190A;T190I 46;369;337;363;414;424 51;374;342;368;419;429 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Comparison of mutation pattern among individuals failing on TDF- and AZT-based regimen (Supplementary Table) showed statistically significant association of K65R mutation with TDF-based regimen (P < 0.001). 2016 Medicine Result HIV K65R 157 161 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Only 1 individual had major PI resistance mutation L90M and 5 had minor PI resistance mutations L89M, V77I, L63P, H69K/R/Q, M36I, K20I/M/R/T, G16E, and L10V/I. 2016 Medicine Result HIV G16E;H69K;H69Q;H69R;K20I;K20M;K20R;K20T;L10I;L10V;L63P;L89M;L90M;M36I;V77I 142;114;114;114;130;130;130;130;152;152;108;96;51;124;102 146;122;122;122;140;140;140;140;158;158;112;100;55;128;106 PI;PI 28;72 30;74 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. The most common NRTI and NNRTI mutation were M184V/I (51.25%) and K103N (36.25%), respectively. 2016 Medicine Result HIV K103N;M184I;M184V 66;45;45 71;52;52 NNRTI;NRTI 25;16 30;20 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. At the subsequent final P10 day 202, M50I was added to R263K and S119R. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K;S119R 37;55;65 41;60;70 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Based on data from these patient-derived isolates, BIC had an improved resistance profile compared to DTG, EVG, and RAL (with mean fold changes of 2.8, 5.8, >106, and >100, respectively; P = 0.04 for BIC versus DTG) and, most notably, against highly INSTI-resistant isolates encoding multiple mutation combinations, such as E92Q/N155H or G140C/S plus Q148R/H/K with or without additional INSTI mutations (P = 0.037 for the 23 isolates with mutations at positions 140 and 148 and P = 0.031 for the 2 isolates with mutations at positions 92 and 155 for BIC versus DTG). 2016 Antimicrobial agents and chemotherapy Result HIV E92Q;G140C;G140S;N155H;Q148H;Q148K;Q148R 324;338;338;329;351;351;351 328;345;345;334;360;360;360 INSTI;INSTI 250;388 255;393 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Both R263K and M50I variants are low-frequency natural polymorphisms of HIV-1 IN. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K 15;5 19;10 IN 78 80 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. By P9 day 174, S153Y waned as S119R concomitantly emerged. 2016 Antimicrobial agents and chemotherapy Result HIV S119R;S153Y 30;15 35;20 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. By P9 day 181, 100% of the viruses contained the M50I/R263K double mutant by clonal sequencing. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K 49;54 53;59 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Clonal sequencing of this P5 virus revealed that even though both S153Y and R263K were detected by population sequencing, no clone actually linked the two mutants. 2016 Antimicrobial agents and chemotherapy Result HIV R263K;S153Y 76;66 81;71 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Compared to the BIC P10 isolate, the DTG P10 isolate displayed somewhat higher EC50 fold-shift values with all tested INSTIs and also encoded the additional S119R substitution. 2016 Antimicrobial agents and chemotherapy Result HIV S119R 157 162 INSTI 118 124 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. During the selection with DTG, mutations S153Y and R263K emerged simultaneously at P4 day 87, followed by S119R and M50I. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K;S119R;S153Y 116;51;106;41 120;56;111;46 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. In a side-by-side comparison with DTG, the same variants displayed comparable or, for the G140S/Q148R mutant, even lower levels of resistance against BIC (Table 6). 2016 Antimicrobial agents and chemotherapy Result HIV G140S;Q148R 90;96 95;101 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. In clonal sequence analyses, 100% of the clones at P10 contained the S119R/R263K double mutant and 65% of the clones contained the M50I/S119R/R263K triple mutant. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K;S119R;R263K;S119R 131;142;136;75;69 135;147;141;80;74 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. In contrast, both the S119R/R263K double mutant and the M50I/S119R/R263K triple mutant were prevalent as individual clones in DTG P10 virus. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K;S119R;R263K;S119R 56;67;61;28;22 60;72;66;33;27 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. In in vitro studies, M50I did not restore the loss in HIV-1 infectivity and viral fitness associated with R263K and conferred only moderate resistance to DTG in combination with R263K. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K;R263K 21;106;178 25;111;183 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. In selections with BIC, mutations R263K and M50I successively emerged at passages 3 (P3; day 47) and 8 (P8; day 156), respectively. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K 44;34 48;39 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. It has emerged in HIV patients on INSTI therapy and is associated with coemergence of the T97A mutation, conferring reduced susceptibility to EVG and RAL but not DTG. 2016 Antimicrobial agents and chemotherapy Result HIV T97A 90 94 INSTI 34 39 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. M50I alone confers virtually no resistance to BIC or the other INSTIs tested. 2016 Antimicrobial agents and chemotherapy Result HIV M50I 0 4 INSTI 63 69 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. M50I has emerged after R263K in previous in vitro DTG selections but has not been observed in patients treated with a first-line regimen containing DTG. 2016 Antimicrobial agents and chemotherapy Result HIV R263K;M50I 23;0 28;4 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Of the five mutations that emerged in EVG breakthrough selections, only T66I is a known mutation associated with INSTI resistance. 2016 Antimicrobial agents and chemotherapy Result HIV T66I 72 76 INSTI 113 118 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. R263K was first reported to be enriched during in vitro selection with EVG. 2016 Antimicrobial agents and chemotherapy Result HIV R263K 0 5 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. R263K was included because it was selected in vitro with DTG and has been reported to emerge in two patient cases following treatment with DTG (50 mg once a day) in combination with a background ARV regimen. 2016 Antimicrobial agents and chemotherapy Result HIV R263K 0 5 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Relative to the wild type, the R263K substitution alone mildly altered the susceptibility to BIC, DTG, and EVG but had no effect against RAL. 2016 Antimicrobial agents and chemotherapy Result HIV R263K 31 36 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. S119R is a natural IN polymorphism prevalent in 1.2% to 6.2% of HIV-1 subtype B isolates from INSTI naive patients. 2016 Antimicrobial agents and chemotherapy Result HIV S119R 0 5 INSTI;IN 94;19 99;21 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. S119R is also associated with other primary INSTI resistance mutations and enhances resistance to INSTIs. 2016 Antimicrobial agents and chemotherapy Result HIV S119R 0 5 INSTI;INSTI 44;98 49;104 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. S153Y substitutions alone conferred resistance similar to that of R263K. 2016 Antimicrobial agents and chemotherapy Result HIV R263K;S153Y 66;0 71;5 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The contribution of R263K and M50I to the phenotypic resistance to BIC and of R263K, S153Y, S119R, and M50I to the phenotypic resistance to DTG was assessed with recombinant site-directed HIV-1 mutant variants and is summarized in Table 7. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;M50I;R263K;R263K;S119R;S153Y 30;103;20;78;92;85 34;107;25;83;97;90 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The EVG selection experiment resulted in the successive emergence of R263K and T66I in P2 day 20 and P6 day 56, respectively. 2016 Antimicrobial agents and chemotherapy Result HIV R263K;T66I 69;79 74;83 Gag 101 103 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The R263K prevalence in treatment-naive HIV-infected patients is extremely low, reaching only ~0.4% of the analyzed patient population. 2016 Antimicrobial agents and chemotherapy Result HIV R263K 4 9 HIV infections 40 52 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The RT M184I mutation that emerged in FTC breakthrough selection is a known FTC resistance-associated mutation, whereas L168I has not been previously associated with FTC resistance. 2016 Antimicrobial agents and chemotherapy Result HIV L168I;M184I 120;7 125;12 RT 4 6 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The S153Y/R263K double mutant had only slightly increased BIC, DTG, and RAL resistance relative to R263K alone but increased resistance to EVG at 29.5-fold. 2016 Antimicrobial agents and chemotherapy Result HIV R263K;R263K;S153Y 10;99;4 15;104;9 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The set of tested mutations included E92Q, Y143R, Q148R, N155H, R263K, E138K/Q148K, G140S/Q148R, E92Q/N155H, and Q148R/N155H. 2016 Antimicrobial agents and chemotherapy Result HIV E138K;E92Q;E92Q;G140S;N155H;N155H;N155H;Q148K;Q148R;Q148R;Q148R;R263K;Y143R 71;37;97;84;57;102;119;77;50;90;113;64;43 76;41;101;89;62;107;124;82;55;95;118;69;48 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. These two mutants displayed slightly elevated BIC, DTG, and RAL resistance relative to that of the R263K mutant and >10-fold resistance to EVG. 2016 Antimicrobial agents and chemotherapy Result HIV R263K 99 104 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Viral breakthrough with these agents contained HIV-RT mutations commonly associated with clinical resistance development (e.g., E138K and M230I for RPV, L100I for EFV, and M184I/V for FTC). 2016 Antimicrobial agents and chemotherapy Result HIV E138K;L100I;M184I;M184V;M230I 128;153;172;172;138 133;158;179;179;143 RT 51 53 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Virus variants that emerged in the presence of EVG or RAL frequently encoded mutations commonly observed in patients treated with these earlier approved INSTIs (e.g., T66I, E92G/V, Q148R, and N155H). 2016 Antimicrobial agents and chemotherapy Result HIV E92G;E92V;N155H;Q148R;T66I 173;173;192;181;167 179;179;197;186;171 INSTI 153 159 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Virus with the M50I/R263K double mutant was equally or slightly less susceptible than virus with the R263K mutant to BIC, DTG, and EVG but remained susceptible to RAL. 2016 Antimicrobial agents and chemotherapy Result HIV M50I;R263K;R263K 15;20;101 19;25;106 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. While D10E, S17N, and D232N are HIV IN polymorphic variants not associated with INSTI resistance, Q177R is a new variant that has not been previously characterized. 2016 Antimicrobial agents and chemotherapy Result HIV D10E;D232N;Q177R;S17N 6;22;98;12 10;27;103;16 INSTI;IN 80;36 85;38 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. While S153Y has been observed to coemerge with R263K in DTG selection, S119R has not been previously observed in DTG selection. 2016 Antimicrobial agents and chemotherapy Result HIV R263K;S119R;S153Y 47;71;6 52;76;11 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. Co-transfection of pCAGGS/Gag and pCAGGS/eCFP-TSG101 with pCAGGS/HA-Vpr A30F did not inhibit Gag/TSG101 co-accumulation when compared with the wild-type Vpr (Fig 3A and 3B). 2016 PloS one Result HIV A30F 72 76 Vpr;Vpr;Gag;Gag 68;153;26;93 71;156;29;96 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. No Vpr incorporation into VLP was detected in the presence of Vpr A30F mutant (Fig 3C), which confirms that this mutant is defective in Gag-mediated Vpr incorporation into virion. 2016 PloS one Result HIV A30F 66 70 Vpr;Vpr;Vpr;Gag 3;62;149;136 6;65;152;139 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. This result correlates with the western blot analysis of VLP production showing partial rescue effect of Vpr A30F mutant against TSG101 overexpression (Fig 3C). 2016 PloS one Result HIV A30F 109 113 Vpr 105 108 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. To verify whether Vpr/Gag interaction directly involves with the rescue effect of Vpr on VLP production, the Vpr A30F mutant which is unable to bind Gag and incorporate into viral particles was used. 2016 PloS one Result HIV A30F 113 117 Vpr;Vpr;Vpr;Gag;Gag 18;82;109;22;149 21;85;112;25;152 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. As aforementioned, one of the hypotheses on the resistance mechanism of K103N is that asparagine at 103 can form a hydrogen bond with the hydroxyl group of tyrosine at position 188; thus blocking the entrance of NNRTIBP and interfering with the binding of NNRTIs (such as EFV, NVP, and DLV) to the pocket. 2016 Viruses Result HIV K103N 72 77 NNRTI 256 262 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. As expected, Y181C RT is highly resistant to NVP and DLV, but not EFV. 2016 Viruses Result HIV Y181C 13 18 RT 19 21 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. As shown in the left panel of Table 2, the EC50s of the NNRTIs against the Y188F/K103N and K103N mutant viruses are within a 2- to 3-fold difference. 2016 Viruses Result HIV K103N;K103N;Y188F 81;91;75 86;96;80 NNRTI 56 62 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Comparable levels of resistance are also conferred by K103N/Y188F RT versus NVP and DLV:with IC50 of 10,033 nM and 1290 nM:which are 72- and 13-fold of resistance, respectively. 2016 Viruses Result HIV K103N;Y188F 54;60 59;65 RT 66 68 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. For example, EFV displayed EC50 of 69 nM and 40 nM against K103N and K103N/Y188F mutants, respectively. 2016 Viruses Result HIV K103N;K103N;Y188F 59;69;75 64;74;80 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. For example, EFV displayed IC50s of 17.0 nM and 10.5 nM against K103N and K103N/Y188F RTs, respectively. 2016 Viruses Result HIV K103N;K103N;Y188F 64;74;80 69;79;85 RT 86 89 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. If the aromaticity of the residues (thus pi-pi stacking) play a major role in the binding of NNRTIs to the NNRTIBP, it is expected that the Y181F and Y188F RTs should maintain, or even increase, the susceptibility of the RTs to NNRTIs:compared with the WT RT:because the mutation(s) enhance the aromaticity of the residues due to the lack of hydroxyl group. 2016 Viruses Result HIV Y181F;Y188F 140;150 145;155 NNRTI;NNRTI;PI;PI;RT;RT;RT 93;228;41;44;156;221;256 99;234;43;46;159;224;258 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. If the hydrogen bond is responsible for the resistance to NNRTIs, NNRTIs that were impacted by the K103N mutation should regain their potency against the Y188F/K103N RT. 2016 Viruses Result HIV K103N;K103N;Y188F 99;160;154 104;165;159 NNRTI;NNRTI;RT 58;66;166 64;72;168 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. In addition, EFV showed an approximately two-fold better potency (IC50 of 0.32 nM) in inhibiting Y188F RT (Table 1, right panel) than WT RT. 2016 Viruses Result HIV Y188F 97 102 RT;RT 103;137 105;139 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. In addition, the K103A and K103E RTs were also produced to investigate if hydrophobic or electrostatic interactions between NNRTIs and K103 side chains play an important role in the binding of NNRTIs to the pocket. 2016 Viruses Result HIV K103A;K103E 17;27 22;32 NNRTI;NNRTI;RT 124;193;33 130;199;36 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. In addition, the Y181F virus also appears to be three-fold more susceptible to all the NNRTIs compared with the WT virus. 2016 Viruses Result HIV Y181F 17 22 NNRTI 87 93 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. In contrast, RT, with the double substitutions of Y181F/Y188F, increased its sensitivity from 3- to 8-fold to all NNRTIs tested in this study. 2016 Viruses Result HIV Y181F;Y188F 50;56 55;61 NNRTI;RT 114;13 120;15 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. It appears that both Y181F and Y188F RTs display similar susceptibility to the NNRTIs, with an approximately two-fold higher susceptibility compared to WT RT. 2016 Viruses Result HIV Y181F;Y188F 21;31 26;36 NNRTI;RT;RT 79;37;155 85;40;157 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. K103A and K103E mutant viruses displayed similar susceptibility to the NNRTIs compared with the WT virus, as opposed to a low level of resistance to the NNRTIs observed in biochemical assay. 2016 Viruses Result HIV K103E;K103A 10;0 15;5 NNRTI;NNRTI 71;153 77;159 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. K103A and K103E substitutions did not confer high levels of resistance to NNRTIs as K103N did in both biochemical and cell-based assays. 2016 Viruses Result HIV K103E;K103N;K103A 10;84;0 15;89;5 NNRTI 74 80 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. K103N is also highly resistant to NVP and DLV, with IC50s of 8100 nM and 2600 nM representing 58- and 27-fold of resistance, respectively. 2016 Viruses Result HIV K103N 0 5 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. On the contrary, Y188L RT displayed significant resistance to all of the three NNRTIs, which is consistent with previous reports. 2016 Viruses Result HIV Y188L 17 22 NNRTI;RT 79;23 85;25 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Similarly, the Y188F substitution did not reduce the affinity of NVP and DLV to the mutant RT. 2016 Viruses Result HIV Y188F 15 20 RT 91 93 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Taken together, these results indicate that the resistance from the K103N substitution may not be attributed to the hydrogen bond between N103 and Y188. 2016 Viruses Result HIV K103N 68 73 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The bio-RTs (WT, K103N, or Y181C) were tested for their susceptibility to various NNRTIs and compared with respective non-biotinylated RTs (non-bio-RTs). 2016 Viruses Result HIV K103N;Y181C 17;27 22;32 NNRTI;RT;RT;RT 82;8;135;148 88;11;138;151 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The left panel of Table 1 indicates that both K103N and K103N/Y188F RTs conferred a similar level of resistance to NNRTIs. 2016 Viruses Result HIV K103N;K103N;Y188F 46;56;62 51;61;67 NNRTI;RT 115;68 121;71 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The tyrosine residue at both positions was mutated to phenylalanine, to give Y181F and/or Y188F to directly test the impact of the aromaticity at the positions on the potency of NNRTIs. 2016 Viruses Result HIV Y181F;Y188F 77;90 82;95 NNRTI 178 184 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The Y188F mutant exhibited similar susceptibility to NVP and DLV, but was more sensitive to EFV inhibition (~4-fold). 2016 Viruses Result HIV Y188F 4 9 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The Y188F/Y181F mutant virus was from approximately 3- to 6-fold more susceptible to all NNRTIs than the WT virus. 2016 Viruses Result HIV Y181F;Y188F 10;4 15;9 NNRTI 89 95 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Therefore, the resistance of K103N may not be due to the lack of hydrophobic interactions between NNRTIs and K103N, owning to shorter aliphatic side chain of asparagine (1 versus 4) because both K103A and K103E possess only one and two carbon aliphatic side chains, respectively. 2016 Viruses Result HIV K103A;K103E;K103N;K103N 195;205;29;109 200;210;34;114 NNRTI 98 104 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Therefore, this suggests that the resistance conferred by K103N/Y188F RT is ascribed to K103N, not Y188F. 2016 Viruses Result HIV K103N;K103N;Y188F;Y188F 58;88;64;99 63;93;69;104 RT 70 72 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. These are the first set of experimental data that directly assess the importance of pi-pi stacking in the binding of NNRTIs to the NNRTIBP, by replacing tyrosine with phenylalanine at positions 181 and 188. 2016 Viruses Result HIV Y181F 153 197 NNRTI;PI;PI 117;84;87 123;86;89 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. These results are consistent with the trend observed in the biochemical assay, which, again, suggest that the hydrogen bond between N103 and Y188 may not contribute to the resistance of K103N to the NNRTIs. 2016 Viruses Result HIV K103N 186 191 NNRTI 199 205 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. To study the resistance mechanism of K103N, several different substitutions were generated at the position of 103 in RT. 2016 Viruses Result HIV K103N 37 42 RT 117 119 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. To test this hypothesis, RT with double substitutions K103N/Y188F was generated to prevent the formation of a hydrogen bond between the two residues (due to the lack of hydroxyl group in phenylalanine). 2016 Viruses Result HIV K103N;Y188F 54;60 59;65 RT 25 27 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. When K103A and K103E RTs were evaluated for their susceptibility to the NNRTIs, K103A and K103E RTs only exhibited low levels of resistance to the NNRTIs (<3-fold versus EFV and <5-fold with NVP and DLV) (Table 1, right panel). 2016 Viruses Result HIV K103A;K103A;K103E;K103E 5;80;15;90 10;85;20;95 NNRTI;NNRTI;RT;RT 72;147;21;96 78;153;24;99 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Yet the Y188F virus appears to be four-fold more susceptible to the NNRTIs than the WT virus (Table 2, right panel). 2016 Viruses Result HIV Y188F 8 13 NNRTI 68 74 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. 2a, I37K (5.9-fold) and N126K (7.2-fold) mutants are more sensitive to VRC01 than WT, based on their corresponding IC50 values. 2016 Retrovirology Result HIV I37K;N126K 4;24 8;29 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. A striking enhancement was observed for anti-CD4bs antibodies, 42F9 (twofold) and 49G2 (1.6-1.7 fold), against C34r, I37K and I37K/L204I mutants. 2016 Retrovirology Result HIV I37K;I37K;L204I 117;126;131 121;130;136 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Additionally, neutralization by VRC01 was unaffected by the combinations of mutations I37K/L204I and N126K/L204I compared to WT. 2016 Retrovirology Result HIV I37K;L204I;L204I;N126K 86;91;107;101 90;96;112;106 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Anti-CD4bs antibodies, 49G2 and 42F9, failed to neutralize WT virus, but the inhibition by these antibodies reached over 50 % against I37K, N126K, and I37K/L204I mutants. 2016 Retrovirology Result HIV I37K;I37K;L204I;N126K 134;151;156;140 138;155;161;145 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. both I37K and C34r have reduced fusion kinetics with respect to WT. 2016 Retrovirology Result HIV I37K 5 9 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. C34-resistance-conferring mutations I37K and N126K are critical for increasing the sensitivity to antibodies directed against either gp120 or gp41. 2016 Retrovirology Result HIV I37K;N126K 36;45 40;50 gp120;gp41 133;142 138;146 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Concerning C34 resistance, we also constructed additional three mutants, I37K, N126K, and N126K/L204I, and we found that I37K contributed most of the resistance to C34 (Additional file 2. 2016 Retrovirology Result HIV I37K;I37K;L204I;N126K;N126K 73;121;96;79;90 77;125;101;84;95 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. For comparison with other fusion inhibitor resistant mutants, we selected three ENF resistant mutants V38A, Q40H, and N43D, because these mutations were frequently observed in ENF treated patients and confer more than tenfold resistance to ENF. 2016 Retrovirology Result HIV N43D;Q40H;V38A 118;108;102 122;112;106 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Furthermore, a slight increase in sCD4 sensitivity by I37K/L204I (threefold) was observed. 2016 Retrovirology Result HIV I37K;L204I 54;59 58;64 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. However, no such change was apparent for N126K or N126K/L204I mutants. 2016 Retrovirology Result HIV L204I;N126K;N126K 56;41;50 61;46;55 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. However, the neutralization sensitivity of the combination of these two mutations (I37K/N126K) was unaltered with respect to WT. 2016 Retrovirology Result HIV I37K;N126K 83;88 87;93 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. In addition to the enhanced neutralization sensitivity to anti-MPER antibodies of the N43D mutant, we also observed an over threefold enhancement of neutralization by anti-V3 antibodies 0.5gamma and KD247 for this mutant. 2016 Retrovirology Result HIV N43D 86 90 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. In contrast, the N126K mutation only influences the neutralization by anti-CD4bs antibodies. 2016 Retrovirology Result HIV N126K 17 22 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. In contrast, two of the three mutations conferring ENF resistance, V38A and Q40H, were unable to affect the neutralization sensitivity by these antibodies. 2016 Retrovirology Result HIV Q40H;V38A 76;67 80;71 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Interestingly, the I37K and N126K mutations were unable to increase the sensitivity to all of these anti-CD4bs antibodies in combination, suggesting that the effects of these mutations on the sensitivity of the viruses to anti-CD4bs antibodies were antagonized by each other. 2016 Retrovirology Result HIV I37K;N126K 19;28 23;33 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Large fluctuations in interfaces between gp41 and gp120 in Env trimer with I37K mutation. 2016 Retrovirology Result HIV I37K 75 79 gp120;gp41;Env 50;41;59 55;45;62 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Mutants with I37K and L204I showed a fivefold increase in their sensitivity to 16G6; however, the sensitivities to KD247 and 0.5gamma were similar between WT and mutants. 2016 Retrovirology Result HIV I37K;L204I 13;22 17;27 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. N126K, the other C34-resistant mutation that is critical for enhanced neutralization, did not affect the antibody binding, and, instead, it abrogated the enhancement effect of I37K in the I37K/N126K mutant. 2016 Retrovirology Result HIV I37K;I37K;N126K;N126K 176;188;193;0 180;192;198;5 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Notably, RMSFs at positions 20-65 in the N-terminal portions of the gp41 extensively increased in all three protomers consisting of the gp41 trimer with the I37K mutation. 2016 Retrovirology Result HIV I37K 157 161 gp41;gp41 68;136 72;140 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Our data suggest that the I37K mutation in gp41 has global effects on the physical properties of the gp120/gp41 trimer. 2016 Retrovirology Result HIV I37K 26 30 gp120;gp41;gp41 101;43;107 106;47;111 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Slow fusion kinetics of C34r and I37K mutants. 2016 Retrovirology Result HIV I37K 33 37 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The C34r with I37K/N126K/L204I mutations was sensitive to neutralization by 4E10 and 10E8 (>threefold). 2016 Retrovirology Result HIV I37K;L204I;N126K 14;25;19 18;30;24 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The effect of N126K on C34 resistance and its fitness cost were lower than that of I37K. 2016 Retrovirology Result HIV I37K;N126K 83;14 87;19 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The envelope concentration for I37K/L204I was similar to the envelope content of L204I (6.5-fold decreases). 2016 Retrovirology Result HIV I37K;L204I;L204I 31;36;81 35;41;86 Env;Env 4;61 12;69 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The I37K mutant, as well as combination mutants that included I37K, also showed a significant decrease in infectivity compared with the WT, similar to the C34r mutant, suggesting that I37K is the major mutation responsible for the reduced infectivity. 2016 Retrovirology Result HIV I37K;I37K;I37K 4;62;184 8;66;188 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The I37K mutation also slightly affected the binding of anti-V3 antibodies, but the effect was marginal compared with that of anti-CD4bs antibodies, 42F9 and 49G2. 2016 Retrovirology Result HIV I37K 4 8 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The I37K mutation enhances the binding affinity of antibodies to epitopes on gp120. 2016 Retrovirology Result HIV I37K 4 8 gp120 77 82 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The I37K mutation had a drastic effect on the binding affinity of the anti-CD4bs antibodies 42F9 and 49G2, and this may be correlated with the enhanced neutralization of C34-resistant viruses by these antibodies. 2016 Retrovirology Result HIV I37K 4 8 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The N43D mutation conferring ENF resistance enhanced the neutralization by anti-MPER antibodies 4E10 (>threefold) and 10E8 (>tenfold). 2016 Retrovirology Result HIV N43D 4 8 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The neutralization potency of the anti-MPER antibody 10E8 was enhanced in I37K (4.5-fold) and I37K/L204I (fivefold) mutants compared with WT. 2016 Retrovirology Result HIV I37K;I37K;L204I 74;94;99 78;98;104 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The presence of E151K and K154N mutations in the 2F5 epitope ELDKWA may explain why SC34r is not sensitive to 2F5 (Additional file 1. 2016 Retrovirology Result HIV E151K;K154N 16;26 21;31 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The resulting data show that sensitivity to sCD4 was significantly higher in I37K (11-fold) and C34r (7.6-fold) mutants than in the WT virus. 2016 Retrovirology Result HIV I37K 77 81 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The results revealed a marked increase in the RMSFs of the gp41 with I37K mutations. 2016 Retrovirology Result HIV I37K 69 73 gp41 59 63 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The results suggest that the I37K mutation induces augmentation of structural fluctuations prominently in the interfaces between gp41 and gp120 in the Env trimer. 2016 Retrovirology Result HIV I37K 29 33 gp120;gp41;Env 138;129;151 143;133;154 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The slight increase in the binding affinity of anti-V3 antibodies in I37K mutants may contribute to the enhanced neutralization of C34-resistant mutants. 2016 Retrovirology Result HIV I37K 69 73 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. There was not a consistent pattern in the Env content for combination of these three mutations; I37K/N126K had an over twofold increase in envelope per p24, whereas N126K/L204I showed an approximately twofold decrease. 2016 Retrovirology Result HIV I37K;L204I;N126K;N126K 96;171;101;165 100;176;106;170 Env;p24;Env 139;152;42 147;155;45 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. These data are consistent with the enhanced neutralization sensitivity of C34r and I37K mutants to 10E8. 2016 Retrovirology Result HIV I37K 83 87 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. These data demonstrate that I37K is critical for C34 resistance in JR-FL, but its presence imposes a significant fitness cost. 2016 Retrovirology Result HIV I37K 28 32 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. These mutants all had the I37K mutation, suggesting that the increased binding affinity of 42F9 and 49G2 to viruses with I37K enhances the neutralization by these antibodies. 2016 Retrovirology Result HIV I37K;I37K 26;121 30;125 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. These results demonstrate that the C34r mutation I37K plays a crucial role in the increased sensitivity to antibodies directed against CD4bs and MPER, even though the enhanced neutralization by anti-V3 antibodies requires all three C34-resistance-associated mutations. 2016 Retrovirology Result HIV I37K 49 53 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. These results indicate that I37K and N126K are the key mutations responsible for increased neutralization sensitivity against anti-CD4bs antibodies, and that the combination of these mutations with L204I caused the C34-resistant phenotype in C34r. 2016 Retrovirology Result HIV I37K;L204I;N126K 28;198;37 32;203;42 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. These results indicate that the I37K mutation induces a conformational change in the envelope trimer, which results in the enhancement of antibody binding owing to improved accessibility to epitopes on gp120. 2016 Retrovirology Result HIV I37K 32 36 Env;gp120 85;202 93;207 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. This change in the envelope content on the surfaces of I37K and C34r pseudoviruses may be partially responsible for their reduced infectivity and higher sensitivity to neutralization. 2016 Retrovirology Result HIV I37K 55 59 Env 19 27 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. This finding suggests that the N126K mutation enhances neutralization by a mechanism other than an increase in the affinity between the envelope and the antibody. 2016 Retrovirology Result HIV N126K 31 36 Env 136 144 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. This lack of correlation between neutralization sensitivity and binding affinity indicates that the enhanced neutralization sensitivity of I37K and N126K to VRC01 is mediated by some other unknown mechanism. 2016 Retrovirology Result HIV I37K;N126K 139;148 143;153 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. This marked increase in the sensitivity to sCD4 in the I37K mutant indicates that the I37K mutation is predominantly responsible for the observed increase in sCD4 sensitivity of C34-resistant variants. 2016 Retrovirology Result HIV I37K;I37K 55;86 59;90 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. This neutralization pattern of I37K and I37K/L204I was similar to that of anti-CD4bs antibodies, 49G2 and 42F9. 2016 Retrovirology Result HIV I37K;I37K;L204I 31;40;45 35;44;50 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. To gain structural insights into the biological effects of the I37K mutation, we conducted structural modeling and MD simulations of the extracellular portion of HIV-1JR-FL gp41 trimer with and without an I37K substitution. 2016 Retrovirology Result HIV I37K;I37K 63;205 67;209 gp41 173 177 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. To investigate the effect on the neutralization sensitivity of mutations conferring fusion inhibitor resistance, we focused on the C34r mutant that comprises three mutations (I37K/N126K/L204I). 2016 Retrovirology Result HIV I37K;L204I;N126K 175;186;180 179;191;185 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. To test this hypothesis, we performed fusion assays for I37K, N126K, N126K/L204I, and C34r mutants. 2016 Retrovirology Result HIV I37K;L204I;N126K;N126K 56;75;62;69 60;80;67;74 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Two ENF-resistant mutants, N43D and Q40H, showed low infectivity compared with WT (approximately tenfold), but the infectivity of the V38A mutant was at the same level as the WT. 2016 Retrovirology Result HIV N43D;Q40H;V38A 27;36;134 31;40;138 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. We are unable to comment on the role of L204I in fitness because it was evaluated by single round infection assay in this study (14). 2016 Retrovirology Result HIV L204I 40 45 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. We constructed fusion inhibitor-resistant mutants by inserting each mutation associated with ENF, C34, SC34, or SC34EK resistance into the Env construct with a JR-FL background (pCXN-JR-FL), and the ENF-resistant clones were designated as V38A, Q40H, and N43D, the C34-resistant clone was designated as C34r, the SC34-resistant clone was designated as SC34r, and the SC34EK-resistant clone was designated as SC34EKr. 2016 Retrovirology Result HIV N43D;Q40H;V38A 255;245;239 259;249;243 Env 139 142 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. We observed a 7- to 11-fold decrease in the envelope content of I37K, N126K, and L204I mutants as compared with WT. 2016 Retrovirology Result HIV I37K;L204I;N126K 64;81;70 68;86;75 Env 44 52 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. Although the data suggest that a suboptimal concentration of RAL appears to increase the propensity of the Y143R mutant to make aberrant integrations, the differences in the fraction of integration sites that were aberrant for the Y143R mutant, comparing the presence and absence of RAL, were not statistically significant. 2016 Retrovirology Result HIV Y143R;Y143R 107;231 112;236 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. Here, we tested the effects of one of the mutants (N155H) in the absence of any added drug in both HOS cells and PBMCs. 2016 Retrovirology Result HIV N155H 51 56 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. In the absence of any added RAL, we found aberrant integrations in infections that were done using the Y143R mutant; however, for the Y143R mutation, the ratio of aberrant to normal integrations was relatively low (1/30), and the fraction of aberrant integrations was not, when compared to infections done with WT IN in the absence of added RAL, statistically significant. 2016 Retrovirology Result HIV Y143R;Y143R 103;134 108;139 IN 314 316 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. The G140S mutation is adjacent to Q148H. 2016 Retrovirology Result HIV G140S;Q148H 4;34 9;39 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. The N155H mutation lies near the sites where the metal ions are bound in the IN active site, and near the 3' end of the viral DNA. 2016 Retrovirology Result HIV N155H 4 9 IN 77 79 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. The Q148H mutation is also near the two metal ions at the IN active site, and the 3' end of the viral DNA. 2016 Retrovirology Result HIV Q148H 4 9 IN 58 60 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. The Y143R mutant specifically causes resistance to RAL; the other two mutants also cause cross-resistance to other INSTIs. 2016 Retrovirology Result HIV Y143R 4 9 INSTI 115 121 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. The Y143R mutation is RAL-specific; Y143 has a pi-pi interaction with the oxadiazole ring of RAL. 2016 Retrovirology Result HIV Y143R 4 9 PI;PI 47;50 49;52 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. This is important because the Y143R mutation raised the IC50 for RAL substantially, (IC50 425 nM, see Table 2), and doses of RAL that would be optimal for WT would be suboptimal for the Y143R mutant. 2016 Retrovirology Result HIV Y143R;Y143R 30;186 35;191 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. This moiety is not present in the other approved INSTIs, and, for that reason, Y143R does not confer cross resistance to the other INSTIs. 2016 Retrovirology Result HIV Y143R 79 84 INSTI;INSTI 49;131 55;137 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. To be sure that the IN mutants would also cause similar aberrant integrations in PBMCs, we infected these cells with the N155H mutant. 2016 Retrovirology Result HIV N155H 121 126 IN 20 22 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. We tested three IN mutants, all of which reduced the susceptibility of the virus (and IN) to RAL, and caused a reduction in the relative infectivity of the single-round HIV vector used in our assay system (Y143R, residual titer is 40-45 % of WT; N155H, ~40 % of WT, and G140S/Q148H, 30-35 % of WT). 2016 Retrovirology Result HIV G140S;N155H;Q148H;Y143R 270;246;276;206 275;251;281;211 IN;IN 16;86 18;88 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. Clearly, Among 1, 152 Shanghai CRF01_AE, the proportion of V179D/E was 7.1% (82/1, 152), higher than all other China CRF01_AE (2.7%, 90/3, 291), P < 0.001. 2016 Scientific reports Result HIV V179D;V179E 59;59 66;66 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. Only 2 networks for M46L, 6 networks for T69N, and 1 network for P225H were found in lineage 1C and 1B, lineage 1D, 1B, 1 A, small lineage, lineage1D, and lineage 1D, respectively. 2016 Scientific reports Result HIV M46L;P225H;T69N 20;65;41 24;70;45 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. Only one individual harbored three mutations including M46I, A62V and T69N. 2016 Scientific reports Result HIV A62V;M46I;T69N 61;55;70 65;59;74 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. Overall, four main network-related drug resistant mutations (some were non-tansmitted drug resistance mutations) were discovered at V179D/E (n = 53), M46L (n = 15), T69N (n = 8), and P225H (n = 2). 2016 Scientific reports Result HIV M46L;P225H;T69N;V179D;V179E 150;183;165;132;132 154;188;169;139;139 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. SH-L1 consisted of four independent sub-lineages (SH-L1A-D), while SH-L2 just presented a small monophyletic lineage. 2016 Scientific reports Result HIV L1A 53 56 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. V179D/E mutation distributed in 26 networks in lineage 1B (n = 8), 1C (n = 33), lineage 2 (n = 3), and small lineage (n = 9). 2016 Scientific reports Result HIV V179D;V179E 0;0 7;7 27704821 Discovery and Development of the Anti-Human Immunodeficiency Virus Drug, Emtricitabine (Emtriva, FTC). The subsequent preclinical development of 524W91 ((-)-FTC) was proceeding at a very brisk pace until the startling observation was made at BW that in HIV passaging studies the compound rapidly selected for a single resistant mutant, M184V, which was 500-1000-fold less sensitive to (-)-FTC compared to wild-type virus. 2016 Accounts of chemical research Result HIV M184V 233 238 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. As described below and in Fig 4B, the evolution in the V1/V2 domains was more complex with several deletions and three low frequency mutations, N148D/S, N150S, S151G, K154R, and N166S. 2016 Virology Result HIV K154R;N148D;N148S;N150S;N166S;S151G 167;144;144;153;178;160 172;151;151;158;183;165 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. As described in the companion article, the original SHIVenv_B3 had high transmission efficiency and established robust infection but in the absence of E32K, this virus was cleared within 100 days and with a similar infection course as with the m349-08 animal. 2016 Virology Result HIV E32K 151 155 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. By day 21, the E32K mutation had not yet appeared in the m165-05 animal. 2016 Virology Result HIV E32K 15 19 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Consensus SHIVenv_B3 found in m328-08 and in m349-08 was also identical to SHIVenv_B3 found in m165-05 at day 14 with the exception of a F319I amino acid change in the V3 loop. 2016 Virology Result HIV F319I 137 142 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Fourteen amino acid changes were observed across gp120 but only the E32K emerged early in the C1 domain dominated in the viral population throughout infeciton. 2016 Virology Result HIV E32K 68 72 gp120 49 54 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. However during the passage in m165-05 animal, SHIVenv_B3 evolved with a mutation in the C1 (E32K) and with multiple amino acid substitutions and deletions in the V1/V2 domain which ultimately introduced a new, putative N linked glycosylation site in V1. 2016 Virology Result HIV E32K 92 96 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Low frequency mutations (<50%) and transient amino acid changes (remaining <67 days) were observed in C1 (V75I and K92N), C2 (Q246R, I272T, A281V), V3 (F317I), V4 (E396K, D398N, E403G, V404G, L405V), V5 (T465I), and C5 regions (R508G) (Fig 3A). 2016 Virology Result HIV A281V;D398N;E396K;E403G;F317I;I272T;K92N;L405V;Q246R;R508G;T465I;V404G;V75I 140;171;164;178;152;133;115;192;126;228;204;185;106 145;176;169;183;157;138;119;197;131;233;209;190;111 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. no E32K mutation. 2016 Virology Result HIV E32K 3 7 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The Env E32K was the only unique and fixed mutation in the entire SHIVenv_B3 genome that was associated with this pathogenesis. 2016 Virology Result HIV E32K 8 12 Env 4 7 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The I143T mutation in the infecting SHIVenv_B3m165 was found at 57% and 100% frequency in the day 98 and 143 virus populations (respectively) and resulted in a new, putative N linked glycosylation site at position 141. 2016 Virology Result HIV I143T 4 9 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The only stable gp120 amino acid difference between animals m165-05 (pathogenic) and m328-08/m349-08 (clearance) was an E32K mutation appearing in 50-68% of clones between days 28-42 then dominating in the m165-05 SHIVenv_B3 quasispecies for the remainder of the infection. 2016 Virology Result HIV E32K 120 124 gp120 16 21 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Thus, even in the absence of E32K mutation, this SHIV_KB9-B3m165-05d21 was still the CCR5-using SHIV providing the highest and most sustained viremia. 2016 Virology Result HIV E32K 29 33 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Thus, we generated the I143T HIV-1env-B3165d98.1/d143. 2016 Virology Result HIV I143T 23 28 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. K103N and M41L were the most frequent SDRMs in the cohort and were present mostly in proportions over 20% in each individual (5.4% and 5.1%, respectively) (Fig 2). 2016 PloS one Result HIV M41L;K103N 10;0 14;5 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. long-standing infection, only M41L showed higher frequency in RI individuals (p = 0.0418) (Fig 6B). 2016 PloS one Result HIV M41L 30 34 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Most PI SDRMs were present only as low-abundance variants under the 5% threshold, including L23I, D30N, I47V, I50V, F53L, I54T, G73S, V82A, N83D, I84V, I85V, N88DS, and L90M (Fig 2). 2016 PloS one Result HIV D30N;F53L;G73S;I47V;I50V;I54T;I84V;I85V;L23I;L90M;N83D;N88D;N88S;V82A 98;116;128;104;110;122;146;152;92;169;140;158;158;134 102;120;132;108;114;126;150;156;96;173;144;163;163;138 PI 5 7 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. One included MSM with a singleton M41L mutation; the other combined females and males (both MSM and heterosexual) with the E138A mutation. 2016 PloS one Result HIV E138A;M41L 123;34 128;38 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Similarly, within NRTI SDRMs, K70ER, V75A, F77L, M184I, T215I, and K219E were only found under the 5% threshold, while D67G and M184V, although present in levels >=5% in some patients, were also mostly present as low-abundance variants <5% (0.8% vs. 2016 PloS one Result HIV D67G;F77L;K219E;K70E;K70R;M184I;M184V;T215I;V75A 119;43;67;30;30;49;128;56;37 123;47;72;35;35;54;133;61;41 NRTI 18 22 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. The presence of individuals with both recent and long-standing infection in the clusters suggests long-term stability of the M41L and E138A mutations. 2016 PloS one Result HIV E138A;M41L 134;125 139;129 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. This increase was mainly NNRTI-associated due to the presence of the polymorphic mutation E138A (86% of cases) and to a lesser extent V108I (14% of cases), which are not considered in the SDRMs list. 2016 PloS one Result HIV E138A;V108I 90;134 95;139 NNRTI 25 30 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. We did not observe significant increasing or decreasing PDR trends for specific ARV drugs (Fig 4C-4E), or for specific DRM frequencies except for the polymorphic mutation E138A, which showed a significant increase from 2011 to 2015 (p = 0.0169) (Fig 5B). 2016 PloS one Result HIV E138A 171 176 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. E45A mutant has been reported to increase the capsid stability, N74D resides in a conserved hydrophobic binding pocket, while P90A, G89V and G94V reside in the CypA-binding loop. 2016 Retrovirology Result HIV G89V;G94V;N74D;P90A;E45A 132;141;64;126;0 136;145;68;130;4 Capsid 46 52 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. In contrast, the effect of TRIM11 on HIV-1 reverse transcription was abolished by capsid mutation G89V, and compromised by capsid mutation P90A. 2016 Retrovirology Result HIV G89V;P90A 98;139 102;143 RT;Capsid;Capsid 43;82;123 64;88;129 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. Meanwhile, another capsid mutant G94V that also resides on the CypA-binding loop was still sensitive to restriction of TRIM11. 2016 Retrovirology Result HIV G94V 33 37 Capsid 19 25 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. MLV and HIV-1 capsid mutant G89V is insensitive to restriction by TRIM11 on early stage of replication. 2016 Retrovirology Result HIV G89V 28 32 Capsid 14 20 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. Similar to wild type HIV-1, the reverse transcription levels of E45A and N74D were restricted in TRIM11-HA expressing cells while enhanced in TRIM11 knockdown cells. 2016 Retrovirology Result HIV E45A;N74D 64;73 68;77 RT 32 53 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Among the 32 HIV-2 Env mutants tested, the one harboring the N659D substitution showed a lower viral release from infected H9 and Jurkat cells compared to HIV-2 wild type virus at two, three and six days post-infection (Figure 3). 2016 Viruses Result HIV N659D 61 66 Env 19 22 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. As expected, we found that particle release at two, three and six days post-infection of the Env N659D virus came back to a level comparable to the wild type (Figure 5A). 2016 Viruses Result HIV N659D 97 102 Env 93 96 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Conversely, the FRET signal was considerably diminished from cells co-expressing BST-2 and HIV-2 Env N659D, therefore illustrating a consistent lack of binding capacity (8.34%, Figure 7C). 2016 Viruses Result HIV N659D 101 106 Env 97 100 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. HIV-2 Env N659D Mutant Is Unable to Bind BST-2. 2016 Viruses Result HIV N659D 10 15 Env 6 9 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. In order to link the poorer release observed for the HIV-2 Env N659D virus to a viral inability to bud from the cell surface, we performed a subtilisin treatment of the infected H9 cells three days post-infection. 2016 Viruses Result HIV N659D 63 68 Env 59 62 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. In order to prove that the lack of viral release of the Env N659D mutant is linked to a deficit of BST-2 antagonism, we generated bst-2 knockout in H9 cells using the CRISPR/Cas9 system. 2016 Viruses Result HIV N659D 60 65 Env;Capsid 56;174 59;176 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Once the cytometer was configured, we exploited this methodology in order to evaluate the capacity of the HIV-2 Env WT, Env 1-749 and Env N659D proteins to link with BST-2. 2016 Viruses Result HIV N659D 138 143 Env;Env;Env 112;120;134 115;123;137 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. This experiment suggested a deficit of BST-2 antagonism for the N659D mutant compared to the Env WT and Env 1-749 viruses. 2016 Viruses Result HIV N659D 64 69 Env;Env 93;104 96;107 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Viral Release of the Env N659D Mutant Is Restored in BST-2-Depleted H9 Cells. 2016 Viruses Result HIV N659D 25 30 Env 21 24 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. We performed RT-qPCR to quantify the number of tethered virions for H9 cells infected with the HIV-2 Env WT, HIV-2 Env 1-749 or HIV-2 Env N659D viruses. 2016 Viruses Result HIV N659D 138 143 Env;Env;Env;RT 101;115;134;13 104;118;137;15 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Among the 6 samples from ARV-naive patients with INSTI major mutations, only one harboured M184V mutation (Supplementary Table 1), known to confer high-level resistance to lamivudine or emtricitabine; no other mutations related to non-nucleoside reverse-transcriptase inhibitors (nNRTIs) and protease inhibitors (PIs) were identified, which was significantly different from the prevalence of resistance mutations to nNRTIs (11.8%) and PIs (2.5%) observed in individuals without major mutations to INSTIs (Table 2). 2016 Scientific reports Result HIV M184V 91 96 NRTI;PR;INSTI;INSTI;NNRTI;NNRTI;PI;PI 235;292;49;497;280;416;313;435 267;300;54;503;286;422;316;438 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Among the INSTI-experienced patients, only one (1.6%) had Q148H/R/K along with two or three of G140A/C/S, L74I and E138A/K/T mutations and were predicted to have high-level resistance to dolutegravir. 2016 Scientific reports Result HIV E138A;E138K;E138T;G140A;G140C;G140S;L74I;Q148H;Q148K;Q148R 115;115;115;95;95;95;106;58;58;58 124;124;124;104;104;104;110;67;67;67 INSTI 10 15 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Among these sequences, Q148H/K/R mutations were found in 91.7% (N = 11) and Y143R mutation in one; yet none of them harboured an N155H mutation. 2016 Scientific reports Result HIV N155H;Q148H;Q148K;Q148R;Y143R 129;23;23;23;76 134;32;32;32;81 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. In INSTI-naive patients, the resistance mutations included L74M (n = 28), E92V (1), Q95K (4), T97A (4), E138AK (3), Y143S (1), V151AL (1), N155S (9), E157Q (11), G163K/R (5), S230R (1) and R263K (4) (Supplementary Table 3). 2016 Scientific reports Result HIV E138A;E138K;E157Q;E92V;G163K;G163R;L74M;N155S;Q95K;R263K;S230R;T97A;V151A;V151L;Y143S 104;104;150;74;162;162;59;139;84;189;175;94;127;127;116 110;110;155;78;169;169;63;144;88;194;180;98;133;133;121 INSTI 3 8 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. On the contrary, the prevalence of P145R was significantly higher in INSTI-naive patients than in raltegravir-experienced patients. 2016 Scientific reports Result HIV P145R 35 40 INSTI 69 74 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. One sequence was identified to harbour Q148R/L74V/P145R mutation, which was predicted to have medium-level resistance to dolutegravir. 2016 Scientific reports Result HIV L74V;P145R;Q148R 45;50;39 49;55;44 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. The prevalence of T97A, G140CAS, E157Q, and V151I was all significantly higher in specimens from raltegravir-experienced patients than those from INSTI-naive patients. 2016 Scientific reports Result HIV E157Q;G140A;G140C;G140S;T97A;V151I 33;24;24;24;18;44 38;31;31;31;22;49 INSTI 146 151 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Thirty patients (47.6%) harboured INSTI-related major mutations, which included 17 with Q148H/K/R mutations, eight with N155H mutations, and six with Y143C/H/R mutations. 2016 Scientific reports Result HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 120;88;88;88;150;150;150 125;97;97;97;159;159;159 INSTI 34 39 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Twelve sequences (19.1%) had Q148H/R/K with one G140A/C/S, L74I, and E138A/K/T, which were predicted to have medium-level resistance to dolutegravir. 2016 Scientific reports Result HIV E138A;E138K;E138T;G140A;G140C;G140S;L74I;Q148H;Q148K;Q148R 69;69;69;48;48;48;59;29;29;29 78;78;78;57;57;57;63;38;38;38 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. K103N, Y181C, G190A, and V108I were the most prevalent mutations associated with NNRTIs resistance and the frequencies were 33.70%, 29.35%, 27.17%, and 27.17%, respectively (Figure 2(b)). 2016 BioMed research international Result HIV G190A;V108I;Y181C;K103N 14;25;7;0 19;30;12;5 NNRTI 81 87 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. The most common mutations associated with drug resistance in NRTIs were M184V (79.45%), M41L (23.29%), M184I (10.96%), and K70R (10.96%) (Figure 2(a)). 2016 BioMed research international Result HIV K70R;M184I;M184V;M41L 123;103;72;88 127;108;77;92 NRTI 61 66 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. The most often combination of NRTIs mutations is M184V + M41L, and its frequency is 6.63%; however, the pattern of NNRTIs mutation combination is an even distribution. 2016 BioMed research international Result HIV M184V;M41L 49;57 54;61 NNRTI;NRTI 115;30 121;35 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. 5C), which is in agreement with our results that showed that the single K92E mutation in strain B.JRFL Nef did not impair its function or expression. 2016 mSphere Result HIV K92E 72 76 Nef 103 106 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. Interestingly, a single point mutation from alanine to valine at position 84 was sufficient to markedly decrease the amount of Nef protein detected by Western blotting. 2016 mSphere Result HIV A84V 44 76 Nef 127 130 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. Introduction of single point mutations into strain C.BR92025 Nef that revert the amino acids at positions 13, 84, and 92 to the conserved residues normally found in Nef (R13W, V84A, and K92E) each resulted in significant but incomplete rescue of Nef-mediated MHC-I downregulation. 2016 mSphere Result HIV K92E;R13W;V84A 186;170;176 190;174;180 Nef;Nef;Nef 61;165;246 64;168;249 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. Nef protein sequence alignments revealed point mutations in the subtype C reference strain (C.BR92025) at positions 13 (W13R), 84 (A84V), and 92 (E92K) that were absent from laboratory strain NL4.3. 2016 mSphere Result HIV A84V;E92K;W13R 131;146;120 135;150;124 Nef 0 3 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. To achieve this, we performed a reciprocal mutational analysis in which we mutated residues 13, 84, and 92 to the amino acids found in strain C.BR92025 Nef, W13R, A84V, and K92E, respectively. 2016 mSphere Result HIV A84V;K92E;W13R 163;173;157 167;177;161 Nef 152 155 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. To determine if the W13R, A84V, and K92E mutations identified in subtype C reference strain C.BR92025 impact Nef activity, we measured a key function of HIV-1 Nef, downregulation of the cell surface receptors MHC-I and CD4. 2016 mSphere Result HIV A84V;K92E;W13R 26;36;20 30;40;24 Nef;Nef 109;159 112;162 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. To fully restore the function of strain C.BR92025 Nef to the levels of strain NL4.3 Nef, a combination of mutations at position 13 and either position 84 (CR13W V84A) or 92 (CR13W E92K) was required. 2016 mSphere Result HIV E92K;V84A 180;161 184;165 Nef;Nef 50;84 53;87 27858889 Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study. More important, 2 out of 9 patients naive for cART (22.2%) hosted variants that carried the K103N (in one patient) and the Y181C (in the other patient) mutations, both directed to drugs of the NNRTI class. 2016 Medicine Result HIV K103N;Y181C 92;123 97;128 NNRTI 193 198 27858889 Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study. This patient was under treatment with drugs from the nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI) drugs and had a variant carrying both the M184V mutation, directed to NRTI drugs and the K103N mutation, directed to NNRTI, although the patient was not treated (nor was previously treated) with drugs of the NNRTI class. 2016 Medicine Result HIV M184V;K103N 173;220 178;225 NRTI;PR;NNRTI;NNRTI;NRTI;NRTI;PI 53;107;248;339;97;201;127 85;115;253;344;101;205;129 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. 3, left and right panel) in its binding capability suggesting that JRCSF is a better Env than JRFL (E168K) with regards to its ability to efficiently bind this class of bNAbs. 2016 Retrovirology Result HIV E168K 100 105 Env 85 88 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. 7, JRCSF (N197D) binds efficiently to PG9 and PGT128 similar to wild-type JRCSF but poorly to the antibodies 17b and 412d. 2016 Retrovirology Result HIV N197D 10 15 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Although JRFL (E168K) showed increased binding to PG9 and PGT145 as compared to JRFL it was not as efficient as JRCSF. 2016 Retrovirology Result HIV E168K 15 20 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. As we observed an extra non-specific protein band migrating close to the expected protein band of molecular weight of gp120 while performing the IP assay of wild type JRCSF Env with cleavage-independent, glycan-directed antibody, 2G12 (data not shown), we performed immunoprecipitation of antigenically more relevant Env, JRCSF (N197D) with cleavage-independent, CD4-bs-directed antibody, VRC01 for determining its efficiency of cleavage on cell surface. 2016 Retrovirology Result HIV N197D 329 334 gp120;Env;Env 118;173;317 123;176;320 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Besides JRFL, which is resistant to PG9 and PG16, was rendered sensitive to these antibodies by an E168K mutation in the V2 loop. 2016 Retrovirology Result HIV E168K 99 104 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Binding to this class of bNabs can be restored in JRFL by the E168K mutation. 2016 Retrovirology Result HIV E168K 62 67 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Both JRFL and JRCSF (N197D), immunoprecipitated with VRC01, shows a single band migrating between the 100 and 150 kDa markers. 2016 Retrovirology Result HIV N197D 21 26 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Furthermore, Asn197 of JRCSF when mutated to Asp (N197D) restores ability of JRCSF to bind to CD4bs-directed antibodies in pseudovirus neutralization assay. 2016 Retrovirology Result HIV N197D 50 55 Asp 45 48 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Furthermore, in pseudovirus neutralization assays it has been shown that mutation of Asn197 of JRCSF to Asp causes JRCSF (N197D) pseudotyped viruses to be efficiently neutralized by b12 and VRC01 suggesting that glycosylation at Asn may play a critical role in the differential binding of JRFL and JRCSF to CD4-bs-directed bNAbs. 2016 Retrovirology Result HIV N197D 122 127 Asp 104 107 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. In addition, we determined whether the CD4-induced epitopes get exposed in JRCSF (N197D) by studying its binding to the antibodies 17b and 412d in comparison to JRFL and wild-type JRCSF. 2016 Retrovirology Result HIV N197D 82 87 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. JRCSF (K168E) was as efficient as JRCSF in its ability to bind PG9 and PGT145. 2016 Retrovirology Result HIV K168E 7 12 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Plasma membrane (PM) fractions of mock-transfected, JRFL and JRCSF (N197D) Env transfected cells were immunoprecipitated with cleavage non-specific bNAb VRC01 as indicated. 2016 Retrovirology Result HIV N197D 68 73 Env 75 78 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Similarly, JRCSF (N197D) binds more efficiently to VRC01 than JRFL in cell surface binding assays. 2016 Retrovirology Result HIV N197D 18 23 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. So we compared JRFL (E168K) with JRCSF for their ability to bind PG9 and PGT145 in FACS based cell surface binding assay. 2016 Retrovirology Result HIV E168K 21 26 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Taken together, these results suggest that JRCSF (N197D) maintains the native conformation. 2016 Retrovirology Result HIV N197D 50 55 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. The mutant JRCSF (N197D) is expressed to a similar extent as JRFL and JRCSF. 2016 Retrovirology Result HIV N197D 18 23 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. There are four amino acid changes between JRCSF and JRFL (K163T, N167D, K168E, and K191S) and one amino acid deletion (K187del) in the V2 domain. 2016 Retrovirology Result HIV K163T;K168E;K187del;K191S;N167D 58;72;119;83;65 63;77;126;88;70 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. To verify whether the single band represents gp120 from cleaved Env, we compared the immunoprecipitated PM fraction of JRCSF (N197D) to the crude cell lysate of the clade B env, YU2 which has been shown to be uncleaved previously. 2016 Retrovirology Result HIV N197D 126 131 gp120;Env;Env 45;64;173 50;67;176 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Two of these mutations viz N167D and K168E are in the strand C of V2 domain which plays a critical role in the ability of Envs to bind V1V2-directed bNAbs. 2016 Retrovirology Result HIV K168E;N167D 37;27 42;32 Env 122 126 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. We checked the binding to glycan and quaternary epitope-dependent bNAbs PG9 and PGT128 to N197D mutated JRCSF in comparison to JRFL and wild-type JRCSF. 2016 Retrovirology Result HIV N197D 90 95 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. YU2 shows a single slower migrating band representing gp160 suggesting that the band in JRCSF (N197D) immunoprecipitated lane is gp120. 2016 Retrovirology Result HIV N197D 95 100 gp120;gp160 129;54 134;59 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. 7C), suggesting that the N74D mutant exhibited an advantage over the WT virus around the time of integration. 2016 Scientific reports Result HIV N74D 25 29 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. Apparently, the N74D change in the capsid allows HIV-1 to escape the action of the factor responsible for the early post-entry block in the marmoset B cell lines. 2016 Scientific reports Result HIV N74D 16 20 Capsid 35 41 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. At early times post-infection, the N74D mutant showed a reduced capacity to synthesize late RT products compared to the WT virus in the marmoset B-LCLs (Figs 6B and 7B). 2016 Scientific reports Result HIV N74D 35 39 RT 92 94 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. However, at late time points after the infection (6/7 days), when all the remaining viral DNA should be integrated, the amount of proviral DNA in the marmoset cells was higher for the N74D mutant than for the WT virus. 2016 Scientific reports Result HIV N74D 184 188 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. However, the combination of the N74D change with the Q50Y and T54Q changes was detrimental to the infectivity of the virus. 2016 Scientific reports Result HIV N74D;Q50Y;T54Q 32;53;62 36;57;66 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. However, the decrease of infectivity observed in the marmoset B-LCLs for the N74D mutant was statistically less significant (p = 0.068), suggesting that in the marmoset cells this mutant was affected to a lesser degree by IFN-alpha treatment. 2016 Scientific reports Result HIV N74D 77 81 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. IFN-alpha treatment also decreased the infectivity of the escape mutant N74D. 2016 Scientific reports Result HIV N74D 72 76 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. In the human B-LCLs, treatment with As2O3 significantly decreased the infectivity of WT HIV-1 and the N74D mutant. 2016 Scientific reports Result HIV N74D 102 106 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. Of interest, we observed that the capsid mutants containing the N74D change, either alone or in combination with the V86M and/or H87Q capsid changes, exhibited increased infectivity (4.9- to 13.9-fold increase) in the marmoset B-LCLs compared to WT viruses. 2016 Scientific reports Result HIV H87Q;N74D;V86M 129;64;117 133;68;121 Capsid;Capsid 34;134 40;140 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. On the contrary, in the marmoset B-LCLs, As2O3 treatment slightly increased the infectivity of HIV-1 WT as well as N74D mutant. 2016 Scientific reports Result HIV N74D 115 119 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. The N74D mutant exhibited reduced nuclear import (formation of 2-LTR circles) in human and marmoset B-LCLs. 2016 Scientific reports Result HIV N74D 4 8 LTR 65 68 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. The production by the N74D mutant of late reverse transcripts was higher in the marmoset B-LCLs compared to the human B-LCLs. 2016 Scientific reports Result HIV N74D 22 26 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. The V86M and H87Q capsid mutants also exhibited increased infectivity in the marmoset cells compared to WT viruses, although the escape was not as efficient as that of the N74D mutant. 2016 Scientific reports Result HIV H87Q;N74D;V86M 13;172;4 17;176;8 Capsid 18 24 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. These results agree with our observation that the marmoset B-LCLs were more permissive to the N74D mutant than to the WT HIV-1 virus. 2016 Scientific reports Result HIV N74D 94 98 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. To examine the mechanism of escape of the N74D capsid mutant in more detail, we studied the kinetics of the synthesis of reverse transcription products by real-time qPCR. 2016 Scientific reports Result HIV N74D 42 46 RT;Capsid 121;47 142;53 27897226 Viral and Host Characteristics of Recent and Established HIV-1 Infections in Kisumu based on a Multiassay Approach. Observed viral mutations included V81I and V81I/V in the protease gene, and V108I/V and K101Q in the reverse transcriptase gene, all of which were intrinsic mutations not associated with ARV exposure. 2016 Scientific reports Result HIV K101Q;V108I;V108V;V81I;V81I;V81V 88;76;76;34;43;43 93;83;83;38;49;49 RT;PR 101;57 122;65 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. As reported previously for WT, some areas including the N-terminal sections of helices 2 (K27-K32) and 4 (Q69-E74) revealed a higher exchange ratio for E12A (Fig 3D). 2016 PloS one Result HIV E12A 152 156 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. At pH 5.5, models 1, 2, 3, 4, and 5 were used for 13, 9, 15, 8, and 35 residues, respectively, to calculate the order parameters for E12A. 2016 PloS one Result HIV E12A 133 137 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Based on the differences in the chemical shifts between the observed and random coil values, there were no global changes in the helical structures caused by either the E12A or L85A mutation (S2 Fig). 2016 PloS one Result HIV E12A;L85A 169;177 173;181 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. By using the values of kint based on the primary sequence, the protection factors for amide protons in each residue of E12A were calculated from kex (Fig 3E). 2016 PloS one Result HIV E12A 119 123 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Calculations revealed that, except for the alpha4-5 loop near H89, the values of kex for WT were slightly higher than those for E12A. 2016 PloS one Result HIV E12A 128 132 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Compared to L85A, the latter cases indicated a stronger protection for the exchange of amide protons throughout the molecule. 2016 PloS one Result HIV L85A 12 16 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Comparison of relaxation data of E12A for pH 7 and 5.5 revealed small changes at the nano- and pico-second time-scale. 2016 PloS one Result HIV E12A 33 37 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Effects of the E12A mutation on amide proton exchange. 2016 PloS one Result HIV E12A 15 19 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Effects of the E12A mutation on dynamic structures. 2016 PloS one Result HIV E12A 15 19 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Effects of the E12A mutation on the carbon and proton chemical shifts. 2016 PloS one Result HIV E12A 15 19 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Effects of the L85A mutation on the chemical shift and amide proton exchange. 2016 PloS one Result HIV L85A 15 19 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Finally, the amide protections of buried resides, which were not sufficient for a 100-ms exchange duration, were plotted around an exchange ratio of 0-0.1 for L85A at pH 7 (Fig 7D), whereas those of E12A (Fig 3D) and WT at pH 7 were plotted at almost zero. 2016 PloS one Result HIV E12A;L85A 199;159 203;163 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. For CA, the values of residues for the entire region of the protein were nearly positive (Fig 2A), indicating a more helical structure in E12A compared to WT. 2016 PloS one Result HIV E12A 138 142 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Furthermore, the effects of the L85A mutation were observed around L31-A37 for CO (Fig 7C). 2016 PloS one Result HIV L85A 32 36 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. However, the values of residues located in the alpha12-loop and helix 5 in E12A were significantly higher than those in other regions. 2016 PloS one Result HIV E12A 75 79 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. However, when comparing the values between WT and E12A, the sequences are identical with the exception of the mutated region. 2016 PloS one Result HIV E12A 50 54 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In addition, the amide proton exchanges were monitored by CLEANEX-PM at pH 5.5 for E12A (Fig 5D). 2016 PloS one Result HIV E12A 83 87 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In addition, the effects of the L85A mutation on the chemical shifts were observed for the residues of helix 1. 2016 PloS one Result HIV L85A 32 36 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In contrast, the difference in the order parameters for each residue was not so clear and monotonous between helices 1 and 5 for E12A (Fig 4B). 2016 PloS one Result HIV E12A 129 133 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In order to confirm the existence of an electrostatic interaction between E12 and H89, the L85A mutation was also produced in this study. 2016 PloS one Result HIV L85A 91 95 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In regards to S2 for E12A, the values for the residues in helix 1 (S9, G10, and L13) and alpha2-3 loop (A45, T53, and C57) were significantly lower at pH 5.5 (Fig 6B) than at pH 7 (Fig 4B). 2016 PloS one Result HIV E12A 21 25 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In the absence of the denaturant, the values of the ellipticity, monitored at 222 nm, for the folded WT and E12A proteins were almost the same (S1 Fig). 2016 PloS one Result HIV E12A 108 112 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Interestingly, the average values of xNOE for the helical regions in E12A (0.81) were slightly higher than those of WT (0.79). 2016 PloS one Result HIV E12A 69 73 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Model 1 (S2), model 2 (S2, Tau-e), model 3 (S2, Rex), model 4 (S2, Tau-e, Rex), and model 5 (S2s, S2f) were used for 16, 20, 19, 18, and 19 residues, respectively, to calculate order parameters for E12A at pH 7, and for 3, 7, 21, 26, and 13 residues, respectively, for the calculations for WT at pH 7. 2016 PloS one Result HIV E12A 198 202 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The amplitude of the value of DeltaG (H2O) of E12A was much higher than that for WT. 2016 PloS one Result HIV E12A 46 50 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The average kex values for amide proton exchanges of the residues in the flexible region were calculated for WT and E12A at pH 7. 2016 PloS one Result HIV E12A 116 120 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The average R2 value for the folded regions of E12A was approximately 15.5 (Fig 3A), and was similar to that of WT. 2016 PloS one Result HIV E12A 47 51 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The average values for WT was 0.040 +- 0.006 (ms-1) with 69 residues and 0.037 +- 0.007 (ms-1) with 75 residues for E12A. 2016 PloS one Result HIV E12A 116 120 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The DeltaG (H2O) values were calculated based on the denaturation curves as:4.85 +- 0.24 kcal mol-1 for WT and:5.92 +- 0.24 kcal mol-1 for E12A. 2016 PloS one Result HIV E12A 139 143 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The effects of the L85A mutation on the protection of the amide proton exchange were plotted in Fig 7D. 2016 PloS one Result HIV L85A 19 23 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The effects of the mutation were examined by comparing chemical shifts between E12A and WT. 2016 PloS one Result HIV E12A 79 83 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The HSQC spectra are presented for WT and E12A at pH 7 (Fig 1A). 2016 PloS one Result HIV E12A 42 46 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The HSQC spectra were superimposed for L85A and WT at pH 7 (Fig 1B). 2016 PloS one Result HIV L85A 39 43 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The m values for WT and E12A were 1.11 +- 0.06 kcal mol-1 M-1 and 1.37 +- 0.06 kcal mol-1 M-1, respectively. 2016 PloS one Result HIV E12A 24 28 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The midpoints for the transitions of the urea denaturation curves (Cm) were 4.38 M for WT and 4.34 M for E12A. 2016 PloS one Result HIV E12A 105 109 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The number of residues for models 3 and 4 including Rex were also low, as observed at pH 7 for E12A compared to WT. 2016 PloS one Result HIV E12A 95 99 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The relaxation studies for E12A were also conducted at pH 5.5 to achieve greater destabilization of E12A (Fig 5A, 5B and 5C). 2016 PloS one Result HIV E12A;E12A 27;100 31;104 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The stability of WT and E12A proteins was compared as a function of the concentration of urea used for denaturation at pH 7 (Table 1). 2016 PloS one Result HIV E12A 24 28 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The unfolding of E12A was more cooperative than that of WT. 2016 PloS one Result HIV E12A 17 21 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The values for Dx, Dy, and Dz were used as 0.115, 0.160, and 0.185 for E12A, and 0.112, 0.180, and 0.228 for WT, respectively. 2016 PloS one Result HIV E12A 71 75 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The values of R2/R1 for E12A were slightly different between pH 7 (Fig 4A) and 5.5 (Fig 6A). 2016 PloS one Result HIV E12A 24 28 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The values of R2/R1 revealed the rotational correlation times for each residue of E12A at pH 7 (Fig 4A). 2016 PloS one Result HIV E12A 82 86 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The values of tau-e and Rex were calculated to verify the order parameter for E12A (S4A and S4B Fig). 2016 PloS one Result HIV E12A 78 82 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The values of tau-e and Rex were calculated to verify the order parameter for E12A at pH 5.5 (S4C and S4D Fig). 2016 PloS one Result HIV E12A 78 82 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. There were small differences in the rate constants between WT and E12A. 2016 PloS one Result HIV E12A 66 70 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Therefore, it was shown that E12A is slightly more stable than WT. 2016 PloS one Result HIV E12A 29 33 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Thermodynamic studies of the E12A mutant. 2016 PloS one Result HIV E12A 29 33 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Additionally, the HIV-C Tat C31S and C31C groups did not differ significantly in log10 viral load (t = 0.18, p = 0.85), average CD4 count (t = -0.1, p = 0.92), duration of infection (t = -0.35, p = 0.73), CES-D scores (t = 0.83, p = 0.41), percentage on cART (chi2(1) = 1.14, p = 0.29), and percentage with detectable viral load (chi2(1) = 1.04, p = 0.31). 2017 Journal of neurovirology Result HIV C31C;C31S 37;28 41;32 Tat 24 27 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. C31C comparison. 2017 Journal of neurovirology Result HIV C31C 0 4 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. DTI differences between C31S and C31C individuals. 2017 Journal of neurovirology Result HIV C31C;C31S 33;24 37;28 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Pearson's correlations were calculated to examine relationships between the imaging metrics and duration of infection, CESD, CD4 count and log10 viral load within all HIV+ individuals, as well as separately for the C31S and C31C groups. 2017 Journal of neurovirology Result HIV C31C;C31S 224;215 228;219 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Results of the MANCOVA revealed no significant differences between the C31S and C31C groups on the volumetric variables (Wilk's Lambda = 0.97, F(6,120) = 0.52, p = 0.78). 2017 Journal of neurovirology Result HIV C31C;C31S 80;71 84;75 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Results of the MANOVAs revealed no significant differences between the C31S and C31C groups on the DTI metrics for the CC (Wilk's Lambda = 0.967, F(3,133) = 1.51, p = 0.22), CING (Wilk's Lambda = 0.991, F(3,133) = 0.38, p = 0.7), ATR (Wilk's Lambda = 0.974, F(2,134) = 1.80, p = 0.1), and UNC (Wilk's Lambda = 0.999, F(2,134) = 0.10, p = 0.9). 2017 Journal of neurovirology Result HIV C31C;C31S 80;71 84;75 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. The only significant correlations were in the C31S group between CD4 count and total white matter (r = -0.43, p value = 0.01), and between log10 viral load and FA (r = -0.40, p value = 0.01) in the ATR (Table 5). 2017 Journal of neurovirology Result HIV C31S 46 50 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. There were no significant differences between C31S (n = 37) or C31C (n = 109) groups with respect to age (t = -1.23, p = 0.22), years of education (t = -1.35, p = 0.10), and sex (chi2(1) = 0.49, p = 0.48). 2017 Journal of neurovirology Result HIV C31C;C31S 63;46 67;50 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Thus, age, years of education, and sex were not included as covariates in subsequent models for the C31S vs. 2017 Journal of neurovirology Result HIV C31S 100 104 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Volumetric differences between C31S and C31C individuals. 2017 Journal of neurovirology Result HIV C31C;C31S 40;31 44;35 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. Eight of nine C309G isolates were MDR and PZA resistant, six of which were also SIT 53. 2016 The American journal of tropical medicine and hygiene Result HIV C309G 14 19 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. Likewise, all 15 of the A403C isolates were of the SIT 53 genotype, MDR, and PZA resistant; 11 of these were from the HDM HIV ward (Table 3). 2016 The American journal of tropical medicine and hygiene Result HIV A403C 24 29 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. Of the 262 TB isolates examined for pncA mutations, the two most common were G145A (a D49N PZAse mutation) and A403C (a T135P PZAse mutation), found in 12% and 5.3% of examined isolates, respectively. 2016 The American journal of tropical medicine and hygiene Result HIV A403C;D49N;G145A;T135P 111;86;77;120 116;90;82;125 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. The only other common pncA mutation significantly associated with MDR and PZA resistance was C309G (a Y103Stop protein mutation), found in 3.4% of examined isolates. 2016 The American journal of tropical medicine and hygiene Result HIV C309G;Y103X 93;102 98;110 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. Nonpolymorphic mutations determining HIV-1 resistance to NNRTIs, G190E, and Y181C were detected only in two HIV-1 specimens circulating in TO. 2016 BioMed research international Result HIV G190E;Y181C 65;76 70;81 NNRTI 57 63 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. Of the mutations influencing NRTI therapy, only the V118I mutation (of the TAM set, efficient only in combination with other resistance mutations) was found. 2016 BioMed research international Result HIV V118I 52 57 NRTI 29 33 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. On the other hand, only the A62VRT mutation of the DR mutations in the pol gene specific of HIV-1 subtype IDUA (V77IPR and A62VRT) was detected at a rate of 8.3%. 2016 BioMed research international Result HIV A62V;A62V;V77I 28;123;112 34;129;119 Pol 71 74 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. Solitary cases of the mutations influencing HIV resistance to PIs in combination with other DR mutations (L33F and A71I) were also recorded. 2016 BioMed research international Result HIV A71I;L33F 115;106 119;111 PI 62 65 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The corresponding mutations are T66I and E157Q. 2016 BioMed research international Result HIV E157Q;T66I 41;32 46;36 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The mutation A62V is an accessory mutation that often occurs in combination with the multinucleoside resistance mutations K65R or Q151M. 2016 BioMed research international Result HIV A62V;K65R;Q151M 13;122;130 17;126;135 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The mutations able to improve HIV-1 reproductive characteristics in the presence of PIs or decrease the PI sensitivity (K20R, T74S, L10V/I, and K20I) were most frequently recordable among the examined HIV-1 variants, mainly in the individuals infected in 2010-2015. 2016 BioMed research international Result HIV K20I;K20R;L10I;L10V;T74S 144;120;132;132;126 148;124;138;138;130 PI;PI 84;104 87;106 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The mutations with a low effect on the resistance to NNRTIs (E138A, V108I, and V90I) also had a low prevalence. 2016 BioMed research international Result HIV E138A;V108I;V90I 61;68;79 66;73;83 NNRTI 53 59 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The sequences encoding HIV-1 IN carried the L74I in 94.1% of the examined subtype A viruses. 2016 BioMed research international Result HIV L74I 44 48 IN 29 31 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. This allows L74I to be regarded as a characteristic mutation for the HIV-1 subtype A population circulating in this area. 2016 BioMed research international Result HIV L74I 12 16 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. A71V and L90M together are considered as resistance mutations for all clinical drugs except DRV and tipranavir. 2016 PloS one Result HIV L90M;A71V 9;0 13;4 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. A71V in PRS17/DRV loses van der Waals contact with Leu89 but retains interaction with Gln92 in comparison to PR/DRV. 2016 PloS one Result HIV A71V 0 4 PR;PR 8;109 10;111 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. A71V, L90M and I93L distal mutations likely propagate alterations to the catalytic site thereby inducing cross resistance to different inhibitors. 2016 PloS one Result HIV I93L;L90M;A71V 15;6;0 19;10;4 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Also, I62V mutation in PRS17 results in loss of van der Waals contact with Pro39 further altering the hinge loop in comparison to PR/DRV. 2016 PloS one Result HIV I62V 6 10 PR;PR 23;130 25;132 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. As reported in the previous section, the L90M mutation forms shortened C-H...O interaction (3.1-3.4 A) between the Met90 side chain and the main chain carbonyl of Asp25 in PRS17/DRV complex instead of longer van der Waals interaction (3.7-3.8 A) observed in PR/DRV complex. 2016 PloS one Result HIV L90M 41 45 Asp;PR;PR 163;172;258 166;174;260 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Comparison of PRS17/DRV with PR20/DRV complex, which has E35D, M36I, S37N and I62V mutations, reveals that the hinge loop conformation of PR20 in subunit A is similar to PRS17 except for absence of the K20R mutation and consequent absence of the ion pair interactions observed between Arg20 and Asp35 in PRS17/DRV (Fig 3B). 2016 PloS one Result HIV E35D;I62V;K20R;M36I;S37N 57;78;202;63;69 61;82;206;67;73 Asp;PR;PR;PR;PR;PR 295;14;29;138;170;304 298;16;31;140;172;306 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Comparison of the DRV-bound complexes of PRS17 and wild type PR/DRV shows a large conformational change in the hinge loop region (residues 34-42) associated with mutations E35D, M36I and S37N in PRS17 (Fig 3A). 2016 PloS one Result HIV E35D;M36I;S37N 172;178;187 176;182;191 PR;PR;PR 41;61;195 43;63;197 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Comparison of the inhibitor-free PRS17 structure with wild-type PR open form (2PC0) shows that the tip of the flaps in PRS17 is twisted from residues G48V to Gly52 (Fig 4B). 2016 PloS one Result HIV G48V 150 154 PR;PR;PR 33;64;119 35;66;121 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Conformational changes associated with mutation cluster of M46L, G48V and I54V are illustrated in Fig 4. 2016 PloS one Result HIV G48V;I54V;M46L 65;74;59 69;78;63 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Curling of flaps by mutations M46L, G48V and I54V. 2016 PloS one Result HIV G48V;I54V;M46L 36;45;30 40;49;34 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Despite the presence of a large number of mutations, PRS17 shares only one mutation (L90M) and a similar substitution (I54L vs I54V) with PR20. 2016 PloS one Result HIV I54L;I54V;L90M 119;127;85 124;131;89 PR;PR 53;138 55;140 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Distal mutations A71V, L90M and I93L perturb the catalytic aspartates. 2016 PloS one Result HIV A71V;I93L;L90M 17;32;23 21;36;27 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Even with no direct contact to inhibitors, L90M induces cross resistance to all clinical protease inhibitors except DRV and tipranavir. 2016 PloS one Result HIV L90M 43 47 PR 89 97 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. G48V is also a minor mutation for atazanavir. 2016 PloS one Result HIV G48V 0 4 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. His69 in PR plays a critical role in autoprocessing, and mutation H69E that introduces a negative charge next to the carboxylate end was shown to impede folding and maturation. 2016 PloS one Result HIV H69E 66 70 PR 9 11 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. However, comparison of structures shows that the conformation of M46L mutation in PRS17/DRV complex differs from that observed in the DRV complex with M46L single mutant (PDB id: 2HS2). 2016 PloS one Result HIV M46L;M46L 65;151 69;155 PR 82 84 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. However, His69 of PR20/DRV retains the ion pair with the carboxylate terminus as in PR/DRV due to absence of I93L mutation. 2016 PloS one Result HIV I93L 109 113 PR;PR 18;84 20;86 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. However, the main chain atoms of 80's loop from Thr80 to V82S shift by ~ 0.8 A in both the subunits of PRS17/DRV in comparison to PR/DRV. 2016 PloS one Result HIV V82S 57 61 PR;PR 103;130 105;132 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. I54V mutation of PRS17/DRV retains van der Waals contacts with the 80's loop as observed in PR/DRV, but loses contacts with the side chain of Ile50' in subunit A. 2016 PloS one Result HIV I54V 0 4 PR;PR 17;92 19;94 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. I93L in PRS17 is likely to further alter L90M mediated perturbation of catalytic aspartates. 2016 PloS one Result HIV L90M;I93L 41;0 45;4 PR 8 10 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Ile50 of PRS17 shows lower differences of 3.3 A and 4.8 A when compared with the open forms of F53L single mutant and FS5929R, respectively. 2016 PloS one Result HIV F53L 95 99 PR 9 11 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In addition to A71V and L90M, I93L is selected as a resistance mutation for atazanavir. 2016 PloS one Result HIV A71V;I93L;L90M 15;30;24 19;34;28 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In addition, the adjacent Met36 side chain interacts with Ile15 and Ile33 in wild-type structures, but the M36I mutation in PRS17/DRV alters the main chain (Calpha RMSD of 2.3 A) such that the shorter Ile36 side chain retains the interactions with Ile15 and I33L in PRS17. 2016 PloS one Result HIV I33L;M36I 258;107 262;111 PR;PR 124;266 126;268 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In addition, the Calpha atoms of M46L in PRS17/DRV dimer are shifted by ~ 0.7-1.0 A compared to its position in single mutant structure. 2016 PloS one Result HIV M46L 33 37 PR 41 43 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In addition, the inhibitor-free PRS17 structure shows no conformational change in Arg8 due to L10I mutation. 2016 PloS one Result HIV L10I 94 98 PR 32 34 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In comparison with PR/DRV complex, substitution of a larger valine side chain, G48V, in PRS17/DRV complex is associated with two alternate conformations of the Phe53 side chain (Fig 4A). 2016 PloS one Result HIV G48V 79 83 PR;PR 19;88 21;90 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PR20, four (D30N, V32I, I47V and I84V) of the 19 mutations alter residues in the active site cavity. 2016 PloS one Result HIV D30N;I47V;I84V;V32I 15;27;36;21 19;31;40;25 PR 3 5 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PR20, L10F mutation acts to break the inter-subunit ion pair between conserved Arg8 and Asp29' by shifting the side chain of Arg8 into a new conformation that makes van der Waals contacts with Phe10 (Fig 2B). 2016 PloS one Result HIV L10F 9 13 Asp;PR 91;3 94;5 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PR20/DRV complex, which lacks M46L and G48V mutations, the side chain of Phe53 shows a similar conformation to that in PR/DRV complex. 2016 PloS one Result HIV G48V;M46L 42;33 46;37 PR;PR 3;122 5;124 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PRS17/DRV complex, however, L10I mutation does not alter the conformation of Arg8 and the ion pair between Arg8/8' and Asp29'/29 is intact for both the subunits as seen for wild type PR (Fig 2B). 2016 PloS one Result HIV L10I 31 35 Asp;PR;PR 122;3;186 125;5;188 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PRS17/DRV complex, M46L side chain has van der Waals contact with both alternate conformations of Phe53. 2016 PloS one Result HIV M46L 22 26 PR 3 5 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PRS17/DRV complex, the side chain of V82S forms van der Waals contacts with P1 phenyl and P1' isobutyl in the two subunits similar to the interactions of Val82 in wild type PR/DRV complex. 2016 PloS one Result HIV V82S 40 44 PR;PR 3;176 5;178 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PRS17/DRV, mutation to a smaller side chain for E35D leads to loss of the ion pair observed in wild type PR between the side chains of Glu35 and flap residue Arg57. 2016 PloS one Result HIV E35D 51 55 PR;PR 3;108 5;110 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In PRS17/DRV, the side chain conformation of M46L is influenced by the altered conformation of Phe53 due to the neighboring G48V mutation, as explained earlier. 2016 PloS one Result HIV G48V;M46L 124;45 128;49 PR 3 5 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In subunit B, the conformation of E35D in PR20/DRV is nearly in-between those of corresponding residues in PR/DRV and PRS17/DRV with a RMSD of 2.6 A between the Calpha of PR20/DRV and PRS17/DRV (Fig 3C). 2016 PloS one Result HIV E35D 34 38 PR;PR;PR;PR;PR 42;107;118;171;184 44;109;120;173;186 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Interestingly, only two mutations of PRS17, G48V in the flaps and V82S in the 80's loop, have contacts with DRV, while the other 15 mutations alter residues outside the active site cavity (Fig 1B). 2016 PloS one Result HIV G48V;V82S 44;66 48;70 PR 37 39 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. L10I mutation does not alter inter-monomer ion pair. 2016 PloS one Result HIV L10I 0 4 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. L90M side chains have identical conformations in PRS17/DRV and PR20/DRV complexes. 2016 PloS one Result HIV L90M 0 4 PR;PR 49;63 51;65 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. L90M single mutants were shown to possess decreased dimer stability and altered catalytic activity. 2016 PloS one Result HIV L90M 0 4 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Like in subunit A, E35D in subunit B of PR20/DRV does not form an ion pair with Lys20. 2016 PloS one Result HIV E35D 19 23 PR 40 42 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. M46L is a major mutation for indinavir resistance and also occurs as minor mutation for all other clinical PIs, except SQV and DRV. 2016 PloS one Result HIV M46L 0 4 PI 107 110 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Molecular dynamics studies predict increased flexibility of the flaps due to rearrangement of hinge loop induced by mutations E35D and M36I. 2016 PloS one Result HIV E35D;M36I 126;135 130;139 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Mutation L10I was shown to decrease viral replication and confer resistance to SQV. 2016 PloS one Result HIV L10I 9 13 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. No interaction was observed between I54V and 80's loop in the single mutant complex, while I54V in PRS17 forms van der Waals and C-H...O interactions with Pro79 of 80's loop. 2016 PloS one Result HIV I54V;I54V 36;91 40;95 PR 99 101 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. PR20 bearing both L90M and A71V mutations exhibits a similar shift in Calpha of A71V. 2016 PloS one Result HIV A71V;A71V;L90M 27;80;18 31;84;22 PR 0 2 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Similar displacement of A71V residue is observed in A71V, V82T and I84V triple mutant structures and was proposed to propagate the shifts through the four stranded beta-sheet (residues 24-71) to the catalytic aspartates resulting in altered activity. 2016 PloS one Result HIV A71V;A71V;I84V;V82T 24;52;67;58 28;56;71;62 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Similarly, I54V is an accessory mutation for all clinical drugs except DRV and nelfinavir. 2016 PloS one Result HIV I54V 11 15 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Single mutation M46L in PR was shown to increase the Ki value for DRV by 10-fold. 2016 PloS one Result HIV M46L 16 20 PR 24 26 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. SQV selects for G48V as a major resistance mutation. 2016 PloS one Result HIV G48V 16 20 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Structural changes associated with neighboring mutations A71V, L90M and I93L are shown in Fig 5. 2016 PloS one Result HIV A71V;I93L;L90M 57;72;63 61;76;67 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The A71V mutation in PRS17 introduces a bulky valine side chain that cannot fit in the helix groove, which results in the displacement of A71V Calpha by 1.3 and 1.1 A in the two subunits of PRS17/DRV in comparison to PR/DRV. 2016 PloS one Result HIV A71V;A71V 4;138 8;142 PR;PR;PR 21;190;217 23;192;219 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The Calpha atoms of mutated I54V are also shifted by ~0.6-1.3 A in the two subunits of PRS17/DRV. 2016 PloS one Result HIV I54V 28 32 PR 87 89 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The conformation of I54V mutation in PRS17/DRV also differs from that observed in the single mutant complex with DRV (PDB id: 3D20) that showed 8-fold increase in the Ki for DRV. 2016 PloS one Result HIV I54V 20 24 PR 37 39 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The corresponding value for PRS17 is 18.7 A and shorter distances of 17.6, 16.2 and 14.9 A are seen for wild-type PR, F53L single mutant and FS5929R, respectively (Fig 4C). 2016 PloS one Result HIV F53L 118 122 PR;PR 28;114 30;116 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The displacement induced by A71V mutation in PRS17 affects adjacent residues His69 and I72V since the Calpha atoms of these residues have shifted by more than 1 A compared with the positions in PR/DRV. 2016 PloS one Result HIV A71V;I72V 28;87 32;91 PR;PR 45;194 47;196 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The equivalent values for the wild-type, PR20 and F53L mutant are 14.5, 13.6, and 8.3 A, respectively. 2016 PloS one Result HIV F53L 50 54 PR 41 43 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The flap in FS5929R crystal structure shows marked deviations from the wild-type flap conformation from Gly48 to F53L. 2016 PloS one Result HIV F53L 113 117 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The flaps of PRS17 harbor 3 mutations, M46L, G48V and I54V. 2016 PloS one Result HIV G48V;I54V;M46L 45;54;39 49;58;43 PR 13 15 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The guanidine head of K20R also forms hydrogen bond interactions with the main chain carbonyl oxygen of E35D. 2016 PloS one Result HIV E35D;K20R 104;22 108;26 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The inhibitor-free and DRV complexes of wild-type PR and PR20 show hydrophobic interactions between the L90/M90 Calpha and Ile93, which are absent in both PRS17 structures due to I93L mutation. 2016 PloS one Result HIV I93L 179 183 PR;PR;PR 50;57;155 52;59;157 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The L90M mutation in PRS17/DRV lies near the main chains of catalytic Asp25/25' and the longer Met90 side chain forms C-H...O interactions with carbonyl oxygen of Asp25/25' that cannot form with the shorter Leu90 in wild type enzyme (Fig 5A). 2016 PloS one Result HIV L90M 4 8 Asp;Asp;PR 70;163;21 73;166;23 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The L90M single mutant complex with DRV exhibited a similar shortened interaction with Asp25 and decreased the PR dimer stability. 2016 PloS one Result HIV L90M 4 8 Asp;PR 87;111 90;113 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The new conformation of Asp35 in PRS17/DRV is anchored by formation of an ion pair with the Arg side chain of K20R. 2016 PloS one Result HIV K20R 110 114 Asp;PR 24;33 27;35 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The open flaps of PR20 structure (3UF3) do not show this twisted flap tip, but the open conformation flap of F53L single mutant structure (2G69) has a similar twist extending from G48 to F53L. 2016 PloS one Result HIV F53L;F53L 109;187 113;191 PR 18 20 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The Phe53 side chain has a single conformation and lacks van der Waals contacts with the side chains of M46L or G48V. 2016 PloS one Result HIV G48V;M46L 112;104 116;108 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The shift, in addition to steric hindrance by I93L mutation, results in loss of ion pair interaction between the side chain of His69 and the charged carboxylate terminus of the other subunit in PRS17/DRV. 2016 PloS one Result HIV I93L 46 50 PR 194 196 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. The single mutation of G48V in the flap results in 29-fold weaker Ki for DRV. 2016 PloS one Result HIV G48V 23 27 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. This conformational change of the hinge loop in PRS17/DRV due to K20R, E35D, M36I and S37D mutations is similar in both subunits. 2016 PloS one Result HIV E35D;K20R;M36I;S37D 71;65;77;86 75;69;81;90 PR 48 50 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. This inactive protease with active site D25N mutation has 22 other mutations (L10I, V11I, L23I, V32I, L33F, S37N, M46I, I47V, I50V, F53L, I54V, Q58E, D60E, L63P, H69R, A71V, G73S, V77I, V82F, L89V, L90M, I93L) including 6 DRV resistance mutations (V11I, V32I, L33F, I47V, I50V, L89V). 2016 PloS one Result HIV A71V;D25N;D60E;F53L;G73S;H69R;I47V;I47V;I50V;I50V;I54V;I93L;L10I;L23I;L33F;L33F;L63P;L89V;L89V;L90M;M46I;Q58E;S37N;V11I;V11I;V32I;V32I;V77I;V82F 168;40;150;132;174;162;120;266;126;272;138;204;78;90;102;260;156;192;278;198;114;144;108;84;248;96;254;180;186 172;44;154;136;178;166;124;270;130;276;142;208;82;94;106;264;160;196;282;202;118;148;112;88;252;100;258;184;190 PR 14 22 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. This interaction between L90M and Asp25/25' is consistent with those observed for L90M single mutant and also L90M in PR20. 2016 PloS one Result HIV L90M;L90M;L90M 25;82;110 29;86;114 Asp;PR 34;118 37;120 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. This structural shift is consistent with those reported for V82A single mutant complexes with DRV, indinavir and SQV, which enable the mutant PR to maintain contacts with inhibitors. 2016 PloS one Result HIV V82A 60 64 PR 142 144 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. This twist is initiated by ~176 degree change in phi angle of G48V compared to Gly48 in wild-type PR. 2016 PloS one Result HIV G48V 62 66 PR 98 100 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Though the conformation of the Val48 side chain is similar in PRS17/DRV and the G48V single mutant complex with DRV (PDB id: CYW), the main chain of PRS17 shows shifts of ~1 A at G48V (subunit A) or ~0.7 A at Phe53 and M46L (subunit B) further indicating that these residues act synergistically. 2016 PloS one Result HIV G48V;G48V;M46L 80;179;219 84;183;223 PR;PR 62;149 64;151 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Though the side chain of neighboring S37D mutation in PRS17/DRV has no contacts with other PRS17 residues, the main chain conformation is rearranged (Calpha RSMD 1.7 A) so that the main chain amide and carbonyl oxygen atoms form hydrogen bonds with one of the alternate side chain conformations of Gln18. 2016 PloS one Result HIV S37D 37 41 PR;PR 54;91 56;93 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Thus the flap mutation cluster of M46L, G48V and I54V alters the conformation of Phe53 and twists the flap tip such that PRS17 has a flap that is nearly open like PR20 but also closer to 80's loop similar to F53L mutant and highly DRV resistant FS5929R. 2016 PloS one Result HIV F53L;G48V;I54V;M46L 208;40;49;34 212;44;53;38 PR;PR 121;163 123;165 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Thus, E35D, M36I and S37D mutations in PRS17 twist the hinge loop thereby breaking the ion pair anchor to the flaps. 2016 PloS one Result HIV E35D;M36I;S37D 6;12;21 10;16;25 PR 39 41 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Thus, L10I mutation in PRS17 does not break the inter-subunit ion pair, unlike the L10F mutation in PR20, and hence does not alter the shape of S2/S2' pocket or the dimer stability of PRS17. 2016 PloS one Result HIV L10F;L10I 83;6 87;10 PR;PR;PR 23;100;184 25;102;186 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Thus, M46L and G48V mutations in PRS17/DRV synergistically alter the Phe53 conformation by steric hindrance. 2016 PloS one Result HIV G48V;M46L 15;6 19;10 PR 33 35 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Unlike PR20, PRS17 has only one mutation V82S in the active site cavity. 2016 PloS one Result HIV V82S 41 45 PR;PR 7;13 9;15 27993614 Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes. Differences in mutations were observed at three codons in integrase associated with integrase drug resistance (A128T, T97A and V151I). 2017 Journal of virological methods Result HIV A128T;T97A;V151I 111;118;127 116;122;132 IN;IN 58;84 67;93 27993614 Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes. Of the four samples with L74I, three were subtype G. 2017 Journal of virological methods Result HIV L74I 25 29 27993614 Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes. The following mutations were observed: Q148K; E138K; G140A in one sample; T97A in two samples; and L74I in four samples. 2017 Journal of virological methods Result HIV E138K;G140A;L74I;Q148K;T97A 46;53;99;39;74 51;58;103;44;78 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. 6A), and we observed that Vif K26R retained its binding capacities with A3G while the binding of Vif H42/43N was decreased ~twofold. 2016 Scientific reports Result HIV K26R 30 34 Vif;Vif 26;97 29;100 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. According to the literature, Vif mutant K26R is still able to interact with A3G, while mutant H42/43N is defective for A3G binding, while retaining binding to the CRL5 complex. 2016 Scientific reports Result HIV K26R 40 44 Vif 29 32 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. Altogether, these results demonstrate that Vif K26R, while defective in A3G degradation through the proteasome pathway, is still fully able to decrease A3G expression through inhibition of A3G mRNA translation, thus demonstrating that these two processes are independent. 2016 Scientific reports Result HIV K26R 47 51 Vif 43 46 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. Importantly, when proteasomal degradation was blocked, wild-type and K26R Vif significantly and similarly inhibited translation of A3G (30-40%) when expressed from wild-type mRNA. 2016 Scientific reports Result HIV K26R 69 73 Vif 74 77 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. Next, we observed that when proteasomal degradation of A3G was not inhibited, expression of A3G from wild-type mRNA was partially reduced (30-40%) by Vif K26R, in comparison to wild-type Vif (60% reduction). 2016 Scientific reports Result HIV K26R 154 158 Vif;Vif 150;187 153;190 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. In our cohort, the commonest clinically significant major NRTI resistance mutations associated with highest levels of reduced susceptibility or virological response were the Non-thymidine analogue mutations (Non-TAMs): M184V:20.7% and K65R:8.0%, while M41L and K70R (both 8.0%) were the commonest TAMs. 2016 BMC research notes Result HIV K65R;K70R;M184V;M41L 235;261;219;252 239;265;224;256 NRTI 58 62 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The commonest major NNRTI resistance mutations known to reduce susceptibility or virological response to NNRTIs were: K103N:19.0%, G190A:7.0% and Y181C:6.0%. 2016 BMC research notes Result HIV G190A;K103N;Y181C 131;118;146 136;123;151 NNRTI;NNRTI 20;105 25;111 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The identified accessory PI resistance mutations that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations included: L10I:27.0%, L10V:12.0% and L10F:5.0% (Table 2). 2016 BMC research notes Result HIV L10F;L10I;L10V 197;170;182 201;174;186 PI;PI;PI 25;68;136 27;70;138 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The most common major PI-resistance mutations associated with the highest levels of phenotypic resistance were: V82A:7.0% and I54V, M46I, L33I (all 5.0%). 2016 BMC research notes Result HIV I54V;L33I;M46I;V82A 126;138;132;112 130;142;136;116 PI 22 24 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. The most common mutations found were M184V (81.2%) reflecting treatment with the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) lamivudine, and K103NS (68.8%) reflecting prior treatment with the non-nucleoside reverse transcriptase inhibitors (NNRTI) nevirapine or efavirenz. 2017 AIDS research and therapy Result HIV K103N;K103S;M184V 158;158;37 164;164;42 NNRTI;RT;NNRTI;NRTI 209;103;258;136 245;124;263;140 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. 1994; Ballesteros and Weinstein 1995), including (1) inactive mutations (Y244A and W248A in TM-6, position VI:09/6.44 and VI:13/6.48) (Steen et al. 2016 Pharmacology research & perspectives Result HIV W248A;Y244A 83;73 88;79 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. 2013, 2014b), two of which with lack of beta-arrestin recruitment (G286F and L203F;G286F), (3) a mutation with removed small-molecule antagonist key anchor point (E283A in TM-7, position VII:06/7.39) (Rosenkilde and Schwartz 2006; Thiele et al. 2016 Pharmacology research & perspectives Result HIV E283A;G286F;G286F;L203F 163;67;83;77 169;73;88;82 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. 2013), (2) constitutively active mutations (L203F in TM-5, position V:13/5.47, G286F in TM-7, position VII:09/7.42, and the double mutation L203F;G286F) (Steen et al. 2016 Pharmacology research & perspectives Result HIV G286F;G286F;L203F;L203F 79;146;44;140 84;151;50;145 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. 2013), but not for Aplaviroc (Y251A in TM-6, position VI:16/6.51) (Maeda et al. 2016 Pharmacology research & perspectives Result HIV Y251A 30 36 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. 5), shedding further light on the mechanism behind the increased surface expression for Y244A, W248A, and Y251A. 2016 Pharmacology research & perspectives Result HIV W248A;Y244A;Y251A 95;88;106 100;93;111 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. 5A), a moderate increase in expression was observed for W248A at high ligand concentration. 2016 Pharmacology research & perspectives Result HIV W248A 56 61 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. 5I and M), indicating that the increased surface expression alone was not causing the increase in fusion for W248A-CCR5. 2016 Pharmacology research & perspectives Result HIV W248A 109 114 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. As expected, no visible change was observed for WT CCR5 and E283A. 2016 Pharmacology research & perspectives Result HIV E283A 60 65 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Both Maraviroc and Aplaviroc displayed potent inhibition of fusion on L203F. 2016 Pharmacology research & perspectives Result HIV L203F 70 75 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Furthermore, Aplaviroc works as a biased agonist on L203F CCR5 as it is capable of stimulating G-protein activity but not beta-arrestin recruitment (Steen et al. 2016 Pharmacology research & perspectives Result HIV L203F 52 57 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. In addition to a surface expression level close to that of WT CCR5, the functionality of L203F in terms of affinity, efficacy, and potency of the endogenous ligands, CCL3 and CCL5, is also similar to WT CCR5 (Steen et al. 2016 Pharmacology research & perspectives Result HIV L203F 89 94 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. In contrast to the TM-6 mutations, the surface expression of E283A. 2016 Pharmacology research & perspectives Result HIV E283A 61 66 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Interestingly, when trying to inhibit fusion for the W248A mutation with a high concentration of either Maraviroc or Aplaviroc, the effect was lost and instead an increase in cell-cell fusion was observed. 2016 Pharmacology research & perspectives Result HIV W248A 53 58 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Likewise, the Y251A mutation - a suggested binding site for Maraviroc (Kondru et al. 2016 Pharmacology research & perspectives Result HIV Y251A 14 19 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. The inactive CCR5 mutations Y244A and W248A (Steen et al. 2016 Pharmacology research & perspectives Result HIV W248A;Y244A 38;28 43;33 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. The luciferase activity for WT CCR5 was matched only by L203F, while a decreased signal was revealed for all of the remaining mutations with a ~50% reduction for Y251A and E283A, followed by Y244A and W248A at ~20-25% of WT level, and with the lowest level of fusion for G286F together with the combined mutation in L203F;G286F. 2016 Pharmacology research & perspectives Result HIV E283A;G286F;G286F;L203F;L203F;W248A;Y244A;Y251A 172;271;322;56;316;201;191;162 177;276;327;61;321;206;196;167 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. The surface expression of all CCR5 mutations was sufficient to allow fusion, which enabled testing of ligands on these mutations, however due to its markedly impaired fusion capabilities, G286F (and the combined mutation L203F;G286F) was excluded from the following studies of ligand interaction. 2016 Pharmacology research & perspectives Result HIV G286F;G286F;L203F 188;227;221 193;232;226 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. This increase was surprisingly more pronounced for the two other mutations in TM-6 (Y244A and Y251A). 2016 Pharmacology research & perspectives Result HIV Y244A;Y251A 84;94 90;99 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Two mutations matched the surface expression of WT CCR5 - L203F and E283A - while the remaining mutations showed a lowered surface expression level. 2016 Pharmacology research & perspectives Result HIV E283A;L203F 68;58 73;63 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. 6 polymorphisms that were not previously identified as being associated with drug resistance per the Stanford database (T39A, K43E, S68N, Q197K, T200V and E224D) were found to have an association with drug resistance mutations. 2017 PloS one Result HIV E224D;K43E;Q197K;S68N;T200V;T39A 155;126;138;132;145;120 160;130;143;136;150;124 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Among these newly found mutations, 7 mutations (E6D, E35D, S37N, I93L, E169D, T200V, and T200E) were considered to be potential drug resistance mutations (Table 2). 2017 PloS one Result HIV E169D;E35D;E6D;I93L;S37N;T200E;T200V 71;53;48;65;59;89;78 76;57;51;69;63;94;83 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. D67N was significantly associated with the other TAMs K70R, H208Y, L210W, and T215Y. 2017 PloS one Result HIV H208Y;K70R;L210W;T215Y;D67N 60;54;67;78;0 65;58;72;83;4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. For example, M41L and D67N had 16 (D218E, E44A, G190S, G196E, H221Y, I142V, K101E, L210W, L228R, L74V, M184V, R211K, T215F, V108I, V118I, and V179I) and nine (E44A, H208Y, H221Y, K70R, L210W, M184V, M41L, R211K, and V90I) target mutations, respectively. 2017 PloS one Result HIV D218E;D67N;E44A;E44A;G190S;G196E;H208Y;H221Y;H221Y;I142V;K101E;K70R;L210W;L210W;L228R;L74V;M184V;M184V;M41L;M41L;R211K;R211K;T215F;V108I;V118I;V179I;V90I 35;22;42;159;48;55;165;62;172;69;76;179;83;185;90;97;103;192;13;199;110;205;117;124;131;142;216 40;26;46;163;53;60;170;67;177;74;81;183;88;190;95;101;108;197;17;203;115;210;122;129;136;147;220 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. However, in the deceased group, M41L was significantly associated with the TAMs (thymidine analogue resistance mutations) D67N, L210W, and T215Y/F. 2017 PloS one Result HIV D67N;L210W;M41L;T215F;T215Y 120;128;32;139;139 126;133;36;146;146 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. In our covariation analysis, four death-associated mutations (T39A, K43E, L74I, and Y181C) were significantly associated with M184V. 2017 PloS one Result HIV K43E;L74I;M184V;T39A;Y181C 68;74;126;62;84 72;78;131;66;89 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. In the deceased group, the covariation pairs between M184V and L74I were highly significant (p < 0.01, OR > 1). 2017 PloS one Result HIV L74I;M184V 63;53 67;58 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. In the network, drug resistance mutations with higher covariation (e.g., M41L, D67N, K101E, K103N, Y181C, M184V, L210W, T215F, and T215I) were more likely to influence the other mutations. 2017 PloS one Result HIV D67N;K101E;K103N;L210W;M184V;M41L;T215F;T215I;Y181C 79;85;92;113;106;73;120;131;99 83;90;97;118;111;77;125;136;104 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. L210W was significantly associated with M41L and T215Y (p < 0.001; R > 1). 2017 PloS one Result HIV M41L;T215Y;L210W 40;49;0 44;54;5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. M41L was significantly associated with T215Y (p < 0.001; R > 1). 2017 PloS one Result HIV T215Y;M41L 39;0 44;4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Most drug resistance mutations (L74I, K103N, Y181C, and G190A) had a high frequency in two groups. 2017 PloS one Result HIV G190A;K103N;L74I;Y181C 56;38;32;45 61;43;36;50 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Non-drug resistant but death-associated polymorphisms T39A may play a role in promoting drug resistance through M184V. 2017 PloS one Result HIV M184V;T39A 112;54 117;58 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Notably, 7 (35%) mutations (L74I, K103N, V106A, Y181C, G190A, T215I and P225H) among those classified were known to be associated with drug resistance according to the HIVdb Program in the Stanford HIV Drug Resistance Database. 2017 PloS one Result HIV G190A;K103N;L74I;P225H;T215I;V106A;Y181C 55;34;28;72;62;41;48 60;39;32;77;67;46;53 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Others 13 (65%) (E6D, Q18H, E35D, S37N, T39A, K43E, S68N, I93L, E169D, Q197K, T200V, T200E and E224D) had not been previously reported to be drug resistance mutations. 2017 PloS one Result HIV E169D;E224D;E35D;E6D;I93L;K43E;Q18H;Q197K;S37N;S68N;T200E;T200V;T39A 64;95;28;17;58;46;22;71;34;52;85;78;40 69;100;32;20;62;50;26;76;38;56;90;83;44 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. The rates of M41L in the deceased and survival groups were not significant. 2017 PloS one Result HIV M41L 13 17 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. There was a correlation between T39A and three mutations (M41L, K43E, and M184V) known to confer drug resistance. 2017 PloS one Result HIV K43E;M184V;M41L;T39A 64;74;58;32 68;79;62;36 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. These polymorphisms include E6D, Q18H, E35D, S37N, T39A, K43E, S68N, L74I, I93L, K103N, V106A, E169D, Y181C, G190A, Q197K, T200V, T200E, T215I, E224D and P225H. 2017 PloS one Result HIV E169D;E224D;E35D;E6D;G190A;I93L;K103N;K43E;L74I;P225H;Q18H;Q197K;S37N;S68N;T200E;T200V;T215I;T39A;V106A;Y181C 95;144;39;28;109;75;81;57;69;154;33;116;45;63;130;123;137;51;88;102 100;149;43;31;114;79;86;61;73;159;37;121;49;67;135;128;142;55;93;107 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. They were all positive Darwin selection mutations (Ka/Ks > 1, LOD > 2), except for V106A and P225H. 2017 PloS one Result HIV P225H;V106A 93;83 98;88 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V118I was significantly associated with M41L, L210W, and T215F in this cluster (p < 0.001; R > 1). 2017 PloS one Result HIV L210W;M41L;T215F;V118I 46;40;57;0 51;44;62;5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. However, the distributions of M184 V/I (chi2 = 7.289, p < 0.05) and M41L (p < 0.05) were significantly different among CRF01_AE, subtype B, and CRF07_BC, respectively. 2017 AIDS research and therapy Result HIV M184I;M184V;M41L 30;30;68 38;38;72 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. In NNRTI coding regions, K103 N was the most frequent mutation, accounting for 15.9% (34/214), followed by Y181C (11.7%, 25/214), G190A (5.1%, 11/214), and G190S (3.7%, 8/214). 2017 AIDS research and therapy Result HIV G190A;G190S;K103N;Y181C 130;156;25;107 135;161;31;112 NNRTI 3 8 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. In NRTI coding regions, M184V/I was the most frequent mutation, accounting for 30.4% (65/214), followed by K70R (8.4%, 18/214), D67N (5.6%, 12/214), M41L (5.4%, 11/214), and T215Y (5.4%, 11/214). 2017 AIDS research and therapy Result HIV D67N;K70R;M184I;M184V;M41L;T215Y 128;107;24;24;149;174 132;111;31;31;153;179 NRTI 3 7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. In PI coding regions, mutations T74S and M46L were found to cause low-level DR to NFV/r, achieving a resistance rate of 1.8% (4/214). 2017 AIDS research and therapy Result HIV M46L;T74S 41;32 45;36 PI 3 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Mutations T74S and M46L in the PI coding region were found in CRF01_AE. 2017 AIDS research and therapy Result HIV M46L;T74S 19;10 23;14 PI 31 33 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. One participant infected through heterosexual contact harbored dual mutations in NRTIs (T69N, M184V, and T215Y) and NNRTIs (K103N and M230L), and presented with high-level resistance to lamivudine (3TC) and emtricitabine (FTC) with M184V, intermediate-level resistance to zidovudine (AZT) and stavudine (D4T) with T215Y, and intermediate or high-level resistance to all NNRTIs with K103N and M230L. 2017 AIDS research and therapy Result HIV K103N;K103N;M184V;M184V;M230L;M230L;T215Y;T215Y;T69N 124;382;94;232;134;392;105;314;88 130;387;99;237;139;397;110;319;92 NNRTI;NNRTI;NRTI 116;370;81 122;376;86 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Two participants harboring M46L and one with M46 V showed low-level resistance to nelfinavir plus ritonavir (NFV/r). 2017 AIDS research and therapy Result HIV M46L;M46V 27;45 31;50 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Two participants infected through homosexual contact and one participant infected through heterosexual contact harbored NRTI mutations D67N and M184V, and NNRTI mutation K103N. 2017 AIDS research and therapy Result HIV D67N;K103N;M184V 135;170;144 139;175;149 NNRTI;NRTI 155;120 160;124 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. After adjustment, participants on zidovudine at failure were more likely to have T215F, T215Y, M41L, K70R, D67N, L210W, type-1 thymidine analog, type-2 thymidine analog, and any thymidine analogue mutations (TAMs); those on tenofovir to have K65R, K70E, Y115F, and M184I; those on efavirenz to have K103N, P225H, Y188L, and L100I; and those on nevirapine to have Y181C and G190A. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV D67N;G190A;K103N;K65R;K70E;K70R;L100I;L210W;M184I;M41L;P225H;T215F;T215Y;Y115F;Y181C;Y188L 107;373;299;242;248;101;324;113;265;95;306;81;88;254;363;313 111;378;304;246;252;105;329;118;270;99;311;86;93;259;368;318 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. In particular, Q151M was seen in 10% of the subtype-C vs <1% of subtype-A/subtype-D. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV Q151M 15 20 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. In particular, V106M occurred in 16% subtype-C compared with 1% A/D, whereas P225H occurred in 2% C vs 7% A and 11% D. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV P225H;V106M 77;15 82;20 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. Supplemental Digital Content, Table 1a, http://links.lww.com/QAI/A970), type-2 thymidine analog DRMs were more common in A and C than in D, K65R and Q151M were more common in C than in both A and D (K65R was more common in A than in D), whereas L210W was less common in C than in both A and D. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R;K65R;L210W;Q151M 140;199;245;149 144;204;250;154 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. Supplemental Digital Content, Table 1b, http://links.lww.com/QAI/A970), (1) E138A, V106M, and Y181C were more common in C than in both A and D, (2) K101E was significantly more common in C and D than in A, (3) H221Y was more common in A and C than in D (and more common in C than in D), (4) V108I was more common in D than in A, and (5) P225H was less common in C than in D (the only DRM significantly less common in C). 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV V106M;Y181C 83;94 88;99 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. The dominant TDRMs in the RT gene were K103N/S (n = 4, 4.6%) and M184V (n = 2, 2.3%), while in the PR gene only M46I/L (n = 1, 1.1%) occurred. 2017 PloS one Result HIV K103N;K103S;M184V;M46I;M46L 39;39;65;112;112 46;46;70;118;118 PR;RT 99;26 101;28 28195728 Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K. From a detailed analysis of the two XN structures it is evident that drug resistant substitutions V32I, I47V and V82I, which add or remove a CH3 group on the side chains, do not significantly alter the hydrophobic contacts. 2017 Journal of medicinal chemistry Result HIV I47V;V32I;V82I 104;98;113 108;102;117 28195728 Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K. Previously, the observation of DRV disordered over two orientations by a 180 flip did not allow us to observe any H atoms in the 0.84 A ultra-high resolution X-ray structure of V32I PR variant in complex with DRV, for many residues showed disorder as well, including main-chain atoms and the catalytic site. 2017 Journal of medicinal chemistry Result HIV V32I 178 182 PR 183 185 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. A pairwise comparison of fold change EC50 values among all patient-derived T97A viruses indicated a strong correlation between EVG and RAL susceptibilities (r2 = 0.74; P < 0.001) (Fig 6). 2017 PloS one Result HIV T97A 75 79 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. All 7 TE patients with emergent T97A alone harbored pre-existing resistance mutations to 1 (n = 3), 2 (n = 2), or 3 (n = 2) antiretroviral classes. 2017 PloS one Result HIV T97A 32 36 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. All 8 patients (1 TN and 7 TE) with emergent T97A alone (i.e., in the absence of primary INSTI RAMs) had HIV-1 subtype B. 2017 PloS one Result HIV T97A 45 49 INSTI 89 94 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Altogether, 55 patient-derived viruses harboring T97A (or T97T/A) alone (i.e., in the absence of primary INSTI RAMs) were tested for phenotypic susceptibility to INSTIs, with data available for 45 isolates (pre-existing T97A: 38 of 47; emergent T97A: 7 of 8) (Table 1 and Fig 3; S1 and S3 Tables, S1 and S3 Figs). 2017 PloS one Result HIV T97A;T97A;T97A;T97A;T97T 49;58;220;245;58 53;64;224;249;64 INSTI;INSTI 105;162 110;168 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Among non-B subtypes, the frequency of T97A was highest among subtype A (33%), A1 (17%), D (19%), and G (11.8%) variants, lowest among subtype AE (0.6%), AG (3.9%), and complex (2.2%) variants, and not detected among subtype A2, C, and F1 variants. 2017 PloS one Result HIV T97A 39 43 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Among non-B variants, the frequency of T97A was highest in both subtype A (5 of 54; 9.3%) and A1 (159 of 1271; 12.5%) variants. 2017 PloS one Result HIV T97A 39 43 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Among the 17 patients with pre-existing T97A and available clinical follow-up (17 of 18), 16 patients [15 TN patients on EVG/COBI/FTC/TDF and 1 TE patient on EVG/r+TDF+DRV] achieved and maintained high rates of virologic suppression (16 of 17 with data; 94%) and 1 patient (described below) experienced virologic rebound (1 of 17 with data; 6%). 2017 PloS one Result HIV T97A 40 44 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Among the 7 patients with emergent T97A alone (i.e., in the absence of primary INSTI RAMs) at virologic failure and available clinical follow-up (7 of 8), 1 patient [1 TN patient on EVG/COBI/FTC/TDF] maintained M184V in reverse transcriptase and T97A in integrase before regaining virologic suppression with no change in therapy (1 of 7 with data; 14%) and 6 TE patients remained viremic (6 of 7 with data; 86%). 2017 PloS one Result HIV M184V;T97A;T97A 211;35;246 216;39;250 RT;IN;INSTI 220;254;79 241;263;84 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Among the 8 patients with emergent T97A alone (1 TN and 7 TE), 13% (1 of 8; 1 TN) of patients had baseline HIV-1 RNA >100,000 copies/mL, 38% (3 of 8; 2 TE and 1 TN) of patients had baseline CD4 count <200 cells/mL, and 63% (5 of 8; 4 TE and 1 TN) of patients had adherence rates <95%. 2017 PloS one Result HIV T97A 35 39 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Among the few patients that experienced virologic failure with INSTI RAMs, the T97A integrase mutation was found to emerge infrequently (11%; 14 of 122). 2017 PloS one Result HIV T97A 79 83 IN;INSTI 84;63 93;68 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Among these 8 patients with emergent T97A alone, 4 patients co-developed a secondary INSTI RAM: V72N (1 TE patient on EVG/r+TDF+DRV), L74M (2 TE patients on RAL+ABC+LPV/r), and G163R (1 TN patient on EVG/COBI/FTC/TDF). 2017 PloS one Result HIV G163R;L74M;T97A;V72N 177;134;37;96 182;138;41;100 INSTI 85 90 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. As a proportion of the total pre-treatment integrase genotypes analyzed, T97A was less frequently detected in TE patients (3 of 703 patients; 0.4%) than TN patients (44 of 2664 patients; 1.7%)(P = 0.01). 2017 PloS one Result HIV T97A 73 77 IN 43 52 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Codon usage at integrase amino acid position 97 was examined from a 4-fold larger data set of patient-derived integrase sequences to define its relation to the prevalence of T97A among non-B subtypes. 2017 PloS one Result HIV T97A 174 178 IN;IN 15;110 24;119 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Consistent with the overall distribution of patients, pre-treatment integrase sequences harboring T97A were unevenly divided among TN (44 of 47 patients; 94%) and TE patients (3 of 47 patients; 6%). 2017 PloS one Result HIV T97A 98 102 IN 68 77 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Emergence of T97A was infrequent among INSTI-treated (treatment-experienced and treatment-naive) patients. 2017 PloS one Result HIV T97A 13 17 INSTI 39 44 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Finally, 38% (18 of 47) of patients with pre-existing T97A enrolled onto an INSTI-based regimen (15 TN and 3 TE). 2017 PloS one Result HIV T97A 54 58 INSTI 76 81 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Finally, more non-B (10 of 18; 56%) than B (8 of 18; 44%) patients harboring pre-existing T97A were enrolled onto an INSTI-based regimen. 2017 PloS one Result HIV T97A 90 94 INSTI 117 122 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Finally, there was no difference between the proportion of patients with reduced EVG susceptibility and the proportion of patients with reduced RAL susceptibility in both the pre-existing and emergent T97A populations (P = 0.682 and P = 1.00, respectively). 2017 PloS one Result HIV T97A 201 205 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, fold change differences in EVG or RAL susceptibility were observed between isolates harboring T97A and T97T/A variants (P = 0.001 and P < 0.001, respectively), with similar findings within the pre- and on-treatment T97A patient populations (Fig 5C). 2017 PloS one Result HIV T97A;T97A;T97A;T97T 103;112;224;112 107;118;228;118 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, only 36% (16 of 45) of patient-derived T97A viruses with data exhibited reduced susceptibility to both EVG and RAL greater than both biological cutoffs. 2017 PloS one Result HIV T97A 48 52 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Impact of T97A alone (pre-existing or emergent) on INSTI-based treatment outcome and resistance development. 2017 PloS one Result HIV T97A 10 14 INSTI 51 56 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In 6 of these 14 patients (EVG, n = 4; RAL, n = 2), the T97A (or T97T/A) integrase mutation emerged in the presence of primary INSTI RAM(s) (N155H, n = 5; E92Q, n = 1) and all had HIV-1 subtype B (Table 1 and Fig 2; S2 Table and S2 Fig). 2017 PloS one Result HIV E92Q;N155H;T97A;T97A;T97T 155;141;56;65;65 159;146;60;71;71 IN;INSTI 73;127 82;132 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In addition, 7 patients harbored >=1 secondary INSTI RAM(s) that persisted from baseline: M50I (n = 2), S119G (n = 1), S119P (n = 3), and S119R (n = 2). 2017 PloS one Result HIV M50I;S119G;S119P;S119R 90;104;119;138 94;109;124;143 INSTI 47 52 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In the remaining 8 patients (EVG, n = 6; RAL, n = 2), the T97A (or T97T/A) integrase mutation emerged alone, in the absence of primary INSTI RAMs (Table 1 and Fig 2; S3 Table and S3 Fig). 2017 PloS one Result HIV T97A;T97A;T97T 58;67;67 62;73;73 IN;INSTI 75;135 84;140 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. No significant differences in EVG or RAL susceptibility were observed between overall pre-existing and emergent T97A populations (P = 0.077 and P = 0.893, respectively) or between pre-existing and emergent T97A populations with reduced EVG or RAL susceptibility greater than biological cutoffs (P = 0.094 and P = 0.670, respectively)(Fig 4A and 4B). 2017 PloS one Result HIV T97A;T97A 112;206 116;210 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. None of these pre-treatment integrase sequences contained primary integrase mutations most often associated with emergent EVG (T66I, E92Q, S147G, Q148R/H/K, and N155H) or RAL (Y143C/R/H, Q148H/K/R, and N155H) resistance. 2017 PloS one Result HIV E92Q;N155H;N155H;Q148H;Q148H;Q148K;Q148K;Q148R;Q148R;S147G;T66I;Y143C;Y143H;Y143R 133;161;202;146;187;146;187;146;187;139;127;176;176;176 137;166;207;155;196;155;196;155;196;144;131;185;185;185 IN;IN 28;66 37;75 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of the 47 patients with pre-existing T97A, the proportion of B (25 of 47; 53%) and non-B (22 of 47; 47%) subtypes were roughly equivalent. 2017 PloS one Result HIV T97A 37 41 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of the 6 TE patients that remained viremic: (i) 2 patients did not meet protocol-defined virologic failure criteria for repeat resistance testing, (ii) 1 patient lost T97A, (iii) 2 patients maintained T97A for 10 and 73 weeks, respectively, without a further significant reduction in INSTI susceptibility, and (iv) 1 patient developed T97T/A at Week 12 and then switched primary INSTI resistance pathways to T66T/A and S147S/G at Week 20 before discontinuing study drug 4 weeks later. 2017 PloS one Result HIV S147G;S147S;T66A;T66T;T97A;T97A;T97A;T97T 419;419;408;408;167;201;335;335 426;426;414;414;171;205;341;341 INSTI;INSTI 284;379 289;384 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of the 7 TE patients with emergent T97A alone (all from Study 183-0145), none developed additional resistance in protease or reverse transcriptase. 2017 PloS one Result HIV T97A 35 39 RT;PR 125;113 146;121 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of the total number of pre-existing T97A (or T97T/A) integrase mutations detected, a slightly greater proportion were detected as full mutants (26 of 47 patients; 55%) than wild-type mixtures (21 of 47; 45%). 2017 PloS one Result HIV T97A;T97A;T97T 36;45;45 40;51;51 IN 53 62 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of these, 50% (4 of 8) of patients developed T97A in year 1 and 50% (4 of 8) of patients developed T97A at a second or subsequent protocol-defined virologic failure visit in year 2 or 3. 2017 PloS one Result HIV T97A;T97A 45;99 49;103 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Other polymorphisms detected at frequencies <0.1% included T97P (ACA-to-CCA transversion), T97I (ACA-to-ATA transition), and A97V (GCA-to-GTA transition). 2017 PloS one Result HIV A97V;T97I;T97P 125;91;59 129;95;63 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Overall, no fold change differences in EVG or RAL susceptibility were observed between B and non-B subtype variants (P = 0.217 and P = 0.672, respectively) or between TN and TE patients (P = 0.349 and P = 0.267, respectively), with similar findings within or between the pre- and on-treatment T97A patient populations (Fig 5A and 5B). 2017 PloS one Result HIV T97A 293 297 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Overall, pre-existence of T97A at screening or baseline (with or without reduced INSTI susceptibility) does not appear to affect treatment response to INSTI-based therapy with two other fully active antiretrovirals. 2017 PloS one Result HIV T97A 26 30 INSTI;INSTI 81;151 86;156 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Patient-derived viruses containing T97A alone may exhibit low-level reductions in susceptibility to EVG and/or RAL. 2017 PloS one Result HIV T97A 35 39 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Pre-existing T97A was more prevalent among non-B subtypes. 2017 PloS one Result HIV T97A 13 17 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Prevalence of pre-existing T97A was infrequent among INSTI-naive (treatment-experienced and treatment-naive) patients. 2017 PloS one Result HIV T97A 27 31 INSTI 53 58 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Similar to our pre-treatment analysis, T97A was more frequently detected in the Los Alamos HIV database among HIV-1 non-B (218 of 8125; 2.7%) than B (37 of 5330; 0.7%) subtypes (P < 0.001). 2017 PloS one Result HIV T97A 39 43 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Some secondary integrase mutations associated with resistance to EVG and/or RAL were detected as natural integrase polymorphisms, most often at very low frequencies (0.5-1%: V72T, L74M, A128T, and G163R) with few exceptions (19%: M50I; 59%: S119P/G/T/R; and 3.8%: E157Q). 2017 PloS one Result HIV A128T;E157Q;G163R;L74M;M50I;S119G;S119P;S119R;S119T;V72T 186;264;197;180;230;241;241;241;241;174 191;269;202;184;234;252;252;252;252;178 IN;IN 15;105 24;114 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Strong correlations were also observed among isolates with pre-existing T97A (r2 = 0.82; P < 0.001) and isolates with emergent T97A alone (r2 = 0.87; P = 0.002) (data not shown). 2017 PloS one Result HIV T97A;T97A 72;127 76;131 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. T97A was the most prevalent low frequency integrase polymorphism detected as GCA at position 97 (255 of 13455; 1.9%), consistent with an ACA-to-GCA transition. 2017 PloS one Result HIV T97A 0 4 IN 42 51 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. T97S was detected as TCA at position 97 (47 of 13455; 0.3%), consistent with an ACA-to-TCA transversion. 2017 PloS one Result HIV T97S 0 4 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Taken together, these results indicate that pre-existence or emergence of T97A alone with reduced susceptibility to EVG and/or RAL is infrequent and not strongly associated with drug selection pressure, subtype, or prior antiretroviral exposure. 2017 PloS one Result HIV T97A 74 78 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The 1 patient [1 TE patient on EVG/r+TDF+DRV] that experienced confirmed viral rebound (HIV-1 RNA = 38,900 copies/mL) at a first protocol-defined virologic failure visit (Week 40) on EVG/r+TDF+DRV maintained T97A and sensitivity to EVG without further development of antiretroviral resistance. 2017 PloS one Result HIV T97A 208 212 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The 1 TN patient with emergent T97A in year 3 (from Study 236-0103) co-developed NRTI (M184V) resistance on EVG/COBI/FTC/TDF at their first protocol-defined virologic failure visit and then later regained virologic suppression by Week 144 at which point study drug was discontinued. 2017 PloS one Result HIV M184V;T97A 87;31 92;35 NRTI 81 85 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The 2 TE patients with the highest EVG FC values (9.94 and 8.95) developed T97A on RAL+ABC+LPV/r and co-developed the secondary INSTI RAM, L74M (or L74L/M). 2017 PloS one Result HIV L74L;L74M;L74M;T97A 148;139;148;75 154;143;154;79 INSTI 128 133 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The frequency of T97A among non-B variants in this larger data set was generally lower than in our pre-treatment data set (Table 2). 2017 PloS one Result HIV T97A 17 21 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The frequency of T97S (31 of 2544; 1.2%) was greater than T97A (1 of 2544; <0.1%) in subtype C variants. 2017 PloS one Result HIV T97A;T97S 58;17 62;21 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The proportion of patients with pre-existing T97A and successful INSTI-treatment outcome (16 of 17 with data; 94%) was similar to the overall treatment population (3759 of 3881; 97%)(P = 0.42). 2017 PloS one Result HIV T97A 45 49 INSTI 65 70 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The T97A (or T97T/A) integrase mutation was detected as an infrequent, naturally occurring integrase polymorphism among all available pre-treatment integrase sequences in 1.4% of patients (47 of 3367) (Table 1 and Fig 2; S1 Table and S1 Fig). 2017 PloS one Result HIV T97A;T97A;T97T 4;13;13 8;19;19 IN;IN;IN 21;91;148 30;100;157 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. This patient had pre-existing NNRTI (V90I) resistance, was noncompliant (overall adherence rate = 84%), and discontinued study drug 21 days later (HIV-1 RNA = 330 copies/mL). 2017 PloS one Result HIV V90I 37 41 NNRTI 30 35 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. To assess potential predictors of T97A emergence in the absence of primary INSTI RAMs, pre-treatment characteristics of HIV-1 RNA and CD4 cell count and on-treatment characteristics of adherence by pill count in returned pill bottles were evaluated (S3 Table). 2017 PloS one Result HIV T97A 34 38 INSTI 75 80 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. When removed from the data set, the fold change difference in EVG susceptibility between pre-existing and emergent T97A patient populations was less significant than reported above (mean FC = 2.94 vs. 2017 PloS one Result HIV T97A 115 119 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. While T97A was infrequently detected among pre-treatment integrase genotypes, T97A was more prevalent in patients harboring non-B (22 of 412; 5.3%) than B (25 of 2826; 0.9%) subtypes (P < 0.001). 2017 PloS one Result HIV T97A;T97A 6;78 10;82 IN 57 66 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. Although most mutations in plasma and CSF were similar, 2 of 3 LLV cases had unique mutations in CSF (case 1: D67N, N348I, E399D, K20R; case 2: P225L, T74A). 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV D67N;E399D;K20R;N348I;P225L;T74A 110;123;130;116;144;151 114;128;134;121;149;155 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. Fourteen of 49 cases with CSF escape had paired plasma and CSF HIV-1 genotypes (29%) with D67N/G reported as a unique CSF mutation twice. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV D67G;D67N 90;90 96;96 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. M184V/I mutations were present in CSF isolates among 17 of 23 cases (74%) with plasma HIV RNA <=50 copies per milliliter. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V 0;0 7;7 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. One case classified as CSF escape had multiple thymidine analogue-associated mutations (TAMs; L210W, T215Y, and M41L) in the presence of the M184I mutation (Table 3) on a regimen of abacavir, lamuvidine, and ritonavir-boosted lopinavir, effectively resulting in PI/r monotherapy in the CNS compartment (No. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV L210W;M184I;M41L;T215Y 94;141;112;101 99;146;116;106 PI 262 264 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. TAMs were present in 20 of 49 cases (40%), most commonly T215Y, D67N, or M41L (Table 4). 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV D67N;M41L;T215Y 64;73;57 68;77;62 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. The most common CSF mutations in RT were M184V and M184I (19% of all CSF mutations identified). 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V 51;41 56;46 RT 33 35 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. The most common PI mutations were V82A/T/F/S/I; V32I mutation was present in 3 cases, and has been associated with high level of resistance in combination with other PI mutations. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV V32I;V82A;V82F;V82I;V82S;V82T 48;34;34;34;34;34 52;46;46;46;46;46 PI;PI 16;166 18;168 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. Two studies reported sequencing the integrase gene in CSF; N155H, L74I, and Q148R mutations were observed as single mutations in the integrase gene, and Y143C was observed in combination with T66I. 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV L74I;N155H;Q148R;T66I;Y143C 66;59;76;192;153 70;64;81;196;158 IN;IN 36;133 45;142 28328548 Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT. This included two cases where participants had acute HIV infection at enrollment (Case 1: K65R was detected in 24.7% of sequences; Case 2: M184I was detected in 3.5% of sequences), and one case where the participant was randomized to the time-driven arm (Case 10: K65R was detected in 3.9% of sequences; M184I was detected in 62.3% of sequences). 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV K65R;K65R;M184I;M184I 90;264;139;304 94;268;144;309 HIV infections 53 66 28328548 Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT. Using a genotyping assay based on population sequencing (ViroSeq), resistance to study drugs was detected in only one of the three cases (Case 10); in that case, only one of the two drug resistance mutations was detected (M184I). 2017 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I 222 227 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. All NNRTI resistance was due to mutation K103N in the reverse transcriptase encoding region. 2017 Clinical infectious diseases Result HIV K103N 41 46 RT;NNRTI 54;4 75;9 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Among individuals starting a suboptimal NNRTI regimen in the presence of K103N, VF occurred in 7/9 individuals: 5 switched the NNRTI compound within 6 months and 2 did not reach virological suppression within 6 months. 2017 Clinical infectious diseases Result HIV K103N 73 78 NNRTI;NNRTI 40;127 45;132 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Among individuals who were tested during therapy failure, K103N was detected in 54% (15/28). 2017 Clinical infectious diseases Result HIV K103N 58 63 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Among individuals with K103N who initiated fully active PI-based cART, VF was observed in one individual, with evident signs of nonadherence. 2017 Clinical infectious diseases Result HIV K103N 23 28 PI 56 58 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Even in these patients we did not find evidence of reversion of K103N. 2017 Clinical infectious diseases Result HIV K103N 64 69 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. In all 7 patients with K103N at baseline, NGS confirmed the presence of this mutation at high prevalence in the viral population (varying from 94.9% to 98.8%). 2017 Clinical infectious diseases Result HIV K103N 23 28 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. K103N was detected in 2 individuals: the first was a basal sequence from an Aruban man who was diagnosed with HIV in Curacao after infection via MSM contact, and the second from a Dutch woman who indicated to be infected in Aruba via heterosexual contact. 2017 Clinical infectious diseases Result HIV K103N 0 5 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Mutation K103N was detected in 25/34 baseline sequences in this cluster. 2017 Clinical infectious diseases Result HIV K103N 9 14 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. NGS was successfully performed on 65/71 samples with wild-type virus and 7 control samples with K103N-virus. 2017 Clinical infectious diseases Result HIV K103N 96 101 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. No additional minority K103N-variants were detected in any of the tested individuals compared to population sequencing. 2017 Clinical infectious diseases Result HIV K103N 23 28 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Patients infected with a K103N-strain were significantly more often MSM, diagnosed in more recent years and more often diagnosed during serologically confirmed recent infection compared to patients infected with wild-type virus. 2017 Clinical infectious diseases Result HIV K103N 25 30 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Phylogenetic analysis of 688 sequences was performed to investigate the origin of the Aruban subtype B sequences and to determine the source of transmission of K103N-variants. 2017 Clinical infectious diseases Result HIV K103N 160 165 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Regimens based on boosted protease inhibitors (PIs) or integrase inhibitors (INSTIs) were initiated in 22 (28%) and 6 (8%) individuals, respectively, mainly due to the detection of K103N at baseline. 2017 Clinical infectious diseases Result HIV K103N 181 186 IN;PR;INSTI;PI 55;26;77;47 64;34;83;50 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. The basal position of the Venezuelan sequences with K103N while on therapy failure suggests that the origin of this large cluster may be associated with an external introduction of HIV-1 to Aruba. 2017 Clinical infectious diseases Result HIV K103N 52 57 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. The clustering of sequences with and without K103N raised the question whether reversion of K103N to wild-type had occurred in those without K103N. 2017 Clinical infectious diseases Result HIV K103N;K103N;K103N 45;92;141 50;97;146 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. The ML tree identified 4 transmission clusters with high-bootstrap and low sequence diversity that contained at least one individual with K103N at baseline (Figure 2). 2017 Clinical infectious diseases Result HIV K103N 138 143 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. The remaining 2 clusters contained pairs of baseline sequences with K103N: (3) 2 Dutch MSM who both indicated to be infected in Aruba and (4) a woman who originated from and was diagnosed with HIV in the Dominican Republic and an Aruban man. 2017 Clinical infectious diseases Result HIV K103N 68 73 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Three K103N cases were identified during therapy failure, of whom 2 were diagnosed with HIV in Venezuela before coming to Aruba. 2017 Clinical infectious diseases Result HIV K103N 6 11 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Three of them selected K103N and were switched to a PI-based regimen. 2017 Clinical infectious diseases Result HIV K103N 23 28 PI 52 54 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Two other single baseline sequences with K103N were found, resulting in a total of 6 independent introductions of variants with K103N into the therapy naive population. 2017 Clinical infectious diseases Result HIV K103N;K103N 41;128 46;133 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Differences in the misinsertion ratios between the WT HIV-2ROD RT and mutants K65R and K65R/Q151M/M184V were small and non-significant except for the misincorporation of A opposite A which was about 4 times less efficient for the single-mutant K65R than for the WT RT. 2017 Scientific reports Result HIV K65R;M184V;Q151M;K65R;K65R 87;98;92;78;244 91;103;97;82;248 RT;RT 63;265 65;267 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. However, the kpol of the nucleotide incorporation reaction on G:T mismatches could not be reliably estimated for the WT and the mutant K65R RT, because both enzymes showed extremely low dTTP binding affinity in this sequence context. 2017 Scientific reports Result HIV K65R 135 139 RT 140 142 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. However, where kinetic parameters were reliably determined, the differences between WT HIV-2 RT and the classwide NRTI-resistant K65R/Q151M/M184V RT were not significant. 2017 Scientific reports Result HIV K65R;M184V;Q151M 129;140;134 133;145;139 NRTI;RT;RT 114;93;146 118;95;148 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In contrast, K65R had minor effects on the catalytic constants determined in these assays, while Q151M produced a modest increase in the catalytic efficiency of the HIV-2 RT, despite reducing the nucleotide binding affinity by two-fold. 2017 Scientific reports Result HIV K65R;Q151M 13;97 17;102 RT 171 173 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In these assays, the WT HIV-2 RT showed 3.5 times higher catalytic efficiency than the triple mutant K65R/Q151M/M184V (Table 1). 2017 Scientific reports Result HIV K65R;M184V;Q151M 101;112;106 105;117;111 RT 30 32 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Mutations K65R and K65R/Q151M/M184V had almost no effect on the intrinsic accuracy of the HIV-2ROD RT, with mutant frequencies being only slightly lower in comparison with that of the WT enzyme. 2017 Scientific reports Result HIV K65R;M184V;Q151M;K65R 19;30;24;10 23;35;29;14 RT 99 101 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Previous studies with prototypic HIV-1 RTs had shown that K65R produced large increases in the fidelity of DNA synthesis in the absence and in the presence of the NRTI-associated resistance mutation V75I. 2017 Scientific reports Result HIV K65R;V75I 58;199 62;203 NRTI;RT 163;39 167;42 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The amino acid substitution M184V alone produced a 3.9-fold reduction of the dNTP binding affinity and was found to be responsible for the lower catalytic efficiency of the K65R/Q151M/M184V HIV-2 RT. 2017 Scientific reports Result HIV K65R;M184V;Q151M;M184V 173;184;178;28 177;189;183;33 RT 196 198 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The catalytic efficiency of nucleotide incorporation was determined for the WT HIV-2ROD RT and mutants K65R, Q151M, M184V and K65R/Q151M/M184V under pre-steady-state conditions, using a 31/21mer heteropolymeric template-primer. 2017 Scientific reports Result HIV K65R;M184V;Q151M;K65R;M184V;Q151M 126;137;131;103;116;109 130;142;136;107;121;114 RT 88 90 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The K65R mutant enzyme showed increased fidelity in comparison with the WT RT in extension reactions with template-primers having a G:G mismatch at their 3' ends. 2017 Scientific reports Result HIV K65R 4 8 RT 75 77 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The same difficulties were also found for the K65R HIV-2 RT in G:A mispair extension assays. 2017 Scientific reports Result HIV K65R 46 50 RT 57 59 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. These assays were used to determine mutation frequencies and error rates for WT HIV-1BH10 and HIV-2ROD RTs, as well as for mutant HIV-2 RTs K65R and K65R/Q151M/M184V. 2017 Scientific reports Result HIV K65R;M184V;Q151M;K65R 149;160;154;140 153;165;159;144 RT;RT 103;136 106;139 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Thus, the frequency of this type of mutations was reduced by less than two-fold in the case of classwide-resistant K65R/Q151M/M184V RT relative to the WT enzyme, while K65R alone produced a mere 1.5-fold increase in nucleotide substitution fidelity. 2017 Scientific reports Result HIV K65R;M184V;Q151M;K65R 115;126;120;168 119;131;125;172 RT 132 134 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. We analysed the nucleotide specificity of HIV-2ROD RT mutants K65R and K65R/Q151M/M184V in misinsertion and mispair extension fidelity assays. 2017 Scientific reports Result HIV K65R;M184V;Q151M;K65R 71;82;76;62 75;87;81;66 RT 51 53 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. An R277K mutation in the Subtype B RT completely abolished viral inhibition by the F1Pk aptamer (Figure 2A and Supplementary Figure S3A), consistent with previous observations that the amino acid identity at position 277 in RT governs enzymatic inhibition by F1Pk aptamers. 2017 Nucleic acids research Result HIV R277K 3 8 RT;RT 35;224 37;226 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. First, this is the first demonstration of viable aptamer resistance in cell culture, and it was achieved without apparent loss of fitness, as infectivity levels were similar for the natural HIV-1 variants (the subtype A and A/E strain) and for point mutations (subtype B R277K mutant) (Figure 1A). 2017 Nucleic acids research Result HIV R277K 271 276 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. For the 6/5AL aptamer, binding was similar for purified subtype B RT and the R277K point mutant (Figure 3A). 2017 Nucleic acids research Result HIV R277K 77 82 RT 66 68 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. For the more potent 6/5AL aptamer, this threshold was reached at 500ng input plasmid for both the Subtype B and R277K mutant viruses; for the F1Pk aptamer, the threshold was reached at 750 ng input plasmid for the Subtype B virus (Figure 4). 2017 Nucleic acids research Result HIV R277K 112 117 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. In contrast, for the R277K mutant RT, the 6/5AL aptamer is encapsidated more efficiently than non-inhibitory transcripts at the lowest doses of input plasmid (Figure 4C and Supplementary Figure S5C) and only this aptamer inhibited infection by the R277K virus (Figure 4D). 2017 Nucleic acids research Result HIV R277K;R277K 21;248 26;253 RT 34 36 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. The F1Pk aptamer bound slightly less well than the 6/5AL aptamer to the Subtype B RT, but it barely interacted at all with the R277K mutant (Figure 3B), consistent with its inability to inhibit the mutant. 2017 Nucleic acids research Result HIV R277K 127 132 RT 82 84 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. The same aptamer failed to inhibit virus carrying RT from two naturally-occurring K277 strains (Subtype A and an A/E recombinant), but inhibition was restored by mutation to R277 (Subtype A/E K277R). 2017 Nucleic acids research Result HIV K277R 192 197 RT 50 52 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. This is in contrast to previous observations of a strong replication defect for N255D/N265D single and double mutations. 2017 Nucleic acids research Result HIV N255D;N265D 80;86 85;91 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. To determine whether differential molecular recognition within aptamer-RT complexes drives relative encapsidation, we measured the binding affinities for F1Pk and 6/5AL aptamers to subtype B RT and to the R277K point mutant. 2017 Nucleic acids research Result HIV R277K 205 210 RT;RT 71;191 73;193 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Among the unclassified TRAMs, K46Q and E28K occurred more commonly in the TDF group and in the thymidine analog group, respectively. 2017 EBioMedicine Result HIV E28K;K46Q 39;30 43;34 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Because M184V/I are established cytosine analog resistance mutations known to increase TDF susceptibility, we excluded M184I from the list of TDF-selected TRAMs. 2017 EBioMedicine Result HIV M184I;M184I;M184V 8;119;8 15;124;15 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Five NRTI-associated TRAMs occurred significantly more commonly in the thymidine analog group including V75I, T165L, M184V, D218E and L228H. 2017 EBioMedicine Result HIV D218E;L228H;M184V;T165L;V75I 124;134;117;110;104 129;139;122;115;108 NRTI 5 9 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. K65R was negatively correlated with both K70Q and K70E. 2017 EBioMedicine Result HIV K70E;K70Q;K65R 50;41;0 54;45;4 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. M184I occurred in 9.4% (264/2873) of individuals in the TDF group and in 2.2% (128/5799) of individuals in the thymidine analog group (p < 0.001). 2017 EBioMedicine Result HIV M184I 0 5 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. M184V occurred in 72.5% (4202/5799) of individuals in the thymidine analog group and in 48.7% (1400/2873) of individuals in the TDF group (p < 0.001). 2017 EBioMedicine Result HIV M184V 0 5 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Of the 83 TRAMs, 16 (21%; 16/83) were established NRTI-associated resistance mutations including A62V, K65R/N, T69deletion, K70E/Q/T/N, L74V/I, V75M/I/L, Y115F, and M184V/I and 40 (48%; 40/83) were established NNRTI-associated resistance mutations. 2017 EBioMedicine Result HIV A62V;K65N;K65R;K70E;K70N;K70Q;K70T;L74I;L74V;M184I;M184V;V75I;V75L;V75M;Y115F 97;103;103;124;124;124;124;136;136;165;165;144;144;144;154 101;109;109;134;134;134;134;142;142;172;172;152;152;152;159 NNRTI;NRTI 210;50 215;54 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Significant genotypic factors associated with an increased VL included the number of TRAMs, the number of NRTI-associated TRAMs, the number of NNRTI-associated TRAMs, M184V/I, K70 mutations, and K65R with and without one or more K65R partners (A62V, S68G/N/D, T69deletion, K70T, V75M and Y115F). 2017 EBioMedicine Result HIV A62V;K65R;K65R;K70T;M184I;M184V;S68D;S68G;S68N;V75M;Y115F 244;195;229;273;167;167;250;250;250;279;288 248;199;233;277;174;174;258;258;258;283;293 NNRTI;NRTI 143;106 148;110 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The largest clique included the following five TRAMs, which were significantly correlated with one another: M184V, K65R, S68N, K70T and Y115F. 2017 EBioMedicine Result HIV K65R;K70T;M184V;S68N;Y115F 115;127;108;121;136 119;131;113;125;141 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The most notable findings among the NRTI-associated TRAMs were an increased proportion of K65R, S68N, and A62V in subtype C viruses, an increased proportion of S68G in CRF01_AE viruses, and an increased proportion of K70E in subtype G viruses. 2017 EBioMedicine Result HIV A62V;K65R;K70E;S68G;S68N 106;90;217;160;96 110;94;221;164;100 NRTI 36 40 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The most strongly correlated pairs (phi > 0.3) were K65R + A62V, K65R + S68N, K65R + S68G, K65R + Y115F, and K70E + L228R. 2017 EBioMedicine Result HIV A62V;K65R;K65R;K65R;K65R;K70E;L228R;S68G;S68N;Y115F 59;52;65;78;91;109;116;85;72;98 63;56;69;82;95;113;121;89;76;103 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The NRTI-associated TRAMs most commonly correlated with other NRTI-associated TRAMs were K65R (n = 10 pairs), M184V (n = 10 pairs), Y115F (n = 7 pairs), A62V (n = 5 pairs), S68N (n = 5 pairs), K70T (n = 5 pairs), K70E (n = 4 pairs), S68G (n = 3 pairs), L74I (n = 3 pairs), and L228R (n = 3 pairs). 2017 EBioMedicine Result HIV A62V;K65R;K70E;K70T;L228R;L74I;M184V;S68G;S68N;Y115F 153;89;213;193;277;253;110;233;173;132 157;93;217;197;282;257;115;237;177;137 NRTI;NRTI 4;62 8;66 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The remaining 26 mutations included 12 mutations at five positions previously associated with NRTI therapy including S68D/G/N/R, T69I, W88S/C, T165L/V, L228H/Q/R; five non-canonical TAMs including D67G, E203K, D218E, and K219N/R; five uncommon previously undifferentiated RTI-associated mutations (I31L/R, T58S, L109I, and K223E) and five previously unreported mutations P4S/T, E28K, K46Q, and S163T. 2017 EBioMedicine Result HIV D218E;D67G;E203K;E28K;I31L;I31R;K219N;K219R;K223E;K46Q;L109I;L228H;L228Q;L228R;P4S;P4T;S163T;S68D;S68G;S68N;S68R;T165L;T165V;T58S;T69I;W88C;W88S 210;197;203;378;298;298;221;221;323;384;312;152;152;152;371;371;394;117;117;117;117;143;143;306;129;135;135 215;201;208;382;304;304;228;228;328;388;317;161;161;161;376;376;399;127;127;127;127;150;150;310;133;141;141 NRTI;RT 94;272 98;275 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. There were 21 viruses with both K65R and K70E but in 16 both K65R and K70E were present as electrophoretic mixtures and in five either K65R or K70E was present as an electrophoretic mixture. 2017 EBioMedicine Result HIV K65R;K65R;K65R;K70E;K70E;K70E 32;61;135;41;70;143 36;65;139;45;74;147 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. There were just two virus sequences with both K65R and K70Q but in each sequence both K65R and K70Q were present as electrophoretic mixtures. 2017 EBioMedicine Result HIV K65R;K65R;K70Q;K70Q 46;86;55;95 50;90;59;99 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Twelve NRTI-associated TRAMs - A62V, K65R/N, S68D/G/N, K70E/Q/T, L74I, V75L and Y115F, and the established cytosine analog resistance mutation M184I, occurred significantly more commonly in the TDF group. 2017 EBioMedicine Result HIV A62V;K65N;K65R;K70E;K70Q;K70T;L74I;M184I;S68D;S68G;S68N;V75L;Y115F 31;37;37;55;55;55;65;143;45;45;45;71;80 35;43;43;63;63;63;69;148;53;53;53;75;85 NRTI 7 11 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Given that integration is diminished by the R263K substitution in short-term infections, we investigated the effect of prolonged infections on the levels of integrated DNA. 2017 mBio Result HIV R263K 44 49 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. H51Y is a substitution that can be selected under DTG pressure secondary to R263K and that further decreases integration compared to the latter mutation. 2017 mBio Result HIV R263K;H51Y 76;0 81;4 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In order to exclude an effect of the R263K substitution on reverse transcription, we performed infections in Jurkat cells with the wild-type (WT) and R263K NL4-3 viruses and measured early and late reverse transcripts at various times after infection. 2017 mBio Result HIV R263K;R263K 37;150 42;155 RT 59 80 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Measuring the RT activity in the cell-free culture fluids showed similar decreases in the production of infectious viral particles over time with the R263K and H51Y R263K mutants. 2017 mBio Result HIV H51Y;R263K;R263K 160;150;165 164;155;170 RT 14 16 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. More importantly, the R263K and H51Y/R263K substitutions resulted in a progressive decrease in integrated DNA between weeks 2 to 4 of infection. 2017 mBio Result HIV H51Y;R263K;R263K 32;22;37 36;27;42 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Prolonged infections with R263K-containing viruses result in gradual decrease in integrated DNA. 2017 mBio Result HIV R263K 26 31 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. R263K does not decrease early and late reverse transcription. 2017 mBio Result HIV R263K 0 5 RT 39 60 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The levels of integrated DNA were decreased below the limit of detection after 1 week when the H51Y/R263K mutant was used. 2017 mBio Result HIV H51Y;R263K 95;100 99;105 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The results show that WT and R263K viruses produced early and late reverse transcripts with comparable kinetics following infection. 2017 mBio Result HIV R263K 29 34 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. This progressive decrease was not observed with the K65R mutant. 2017 mBio Result HIV K65R 52 56 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. We also used a virus bearing the K65R RT substitution as a control. 2017 mBio Result HIV K65R 33 37 RT 38 40 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. A significant association between subtype C and an increased risk of K65R was observed with tenofovir, abacavir and didanosine. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 69 73 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Among patients who had never taken tenofovir, the drug that selects most strongly for K65R, the mutation remained commonly observed and the subtype difference persisted (Figure 1d). 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 86 90 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. As expected, patients taking zidovudine were less likely (adjusted OR = 0.41, 95% CI = 0.29-0.59) to develop K65R. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 109 113 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Current exposure to abacavir and didanosine were also significant predictors of K65R, but no effect of exposure to stavudine (either previous or current) was observed. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 80 84 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. However, it is not possible to draw conclusions about the relative selective pressure exerted by different NRTIs from this univariate analysis since patients received many different permutations of the drugs and as K65R may have been selected on a single occasion or multiple occasions. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 215 219 NRTI 107 112 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Overall, K65R was detected in 446 (8.7%) patients. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 9 13 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The association between K65R detection and viral subtype was consistently observed regardless of current or previous exposure to the NRTIs that select for K65R (Figure 1). 2017 The Journal of antimicrobial chemotherapy Result HIV K65R;K65R 24;155 28;159 NRTI 133 138 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The frequency of K65R was highest among patients infected with a subtype C virus (14.2%; 115/810), approximately double that observed for subtype B (7.8%; 267/3410) and subtype non-B/C (7.3%; 64/880). 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 17 21 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The strongest drug selection pressure was observed for tenofovir, with patients who were taking this drug at the time of the resistance test being 5.03-fold (95% CI = 3.90-6.50) more likely to have developed K65R compared with patients who had never taken tenofovir. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 208 212 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. This analysis confirmed the highly significant difference in the frequency of K65R among subtype C patients compared with subtype B patients (adjusted OR = 2.02, 95% CI = 1.55-2.62, P < 0.001). 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 78 82 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. This effect was not found to be significant amongst those currently on stavudine due to a smaller number of K65R mutations occurring in this group. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 108 112 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. With the exception of tenofovir, previous drug exposure had no effect on the development of K65R, which reflects the low replicative capacity of this mutation. 2017 The Journal of antimicrobial chemotherapy Result HIV K65R 92 96 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. Emerging NRTI RAMs were M41L, L74V, K219Q (1/49), D67N, M184I, T215Y (2/49), and M184V (3/49). 2017 SAGE open medicine Result HIV D67N;K219Q;L74V;M184I;M184V;M41L;T215Y 50;36;30;56;81;24;63 54;41;34;61;86;28;68 NRTI 9 13 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. Other etravirine RAMs that each emerged in <5 VFs were V90I, E138G, E138K, and E138Q. 2017 SAGE open medicine Result HIV E138G;E138K;E138Q;V90I 61;68;79;55 66;73;84;59 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. PI RAMs that emerged were L10I and A71T, each once (1/49). 2017 SAGE open medicine Result HIV A71T;L10I 35;26 39;30 PI 0 2 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. The most frequently emerging etravirine RAMs (developing in >=5 VFs) were Y181C (18/49), E138A (5/49), and M230L (5/49). 2017 SAGE open medicine Result HIV E138A;M230L;Y181C 89;107;74 94;112;79 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. The most frequently observed baseline etravirine RAMs were G190A (18/151), V90I (15/151), A98G (10/151), and K101E (9/151) (Supplementary Figure 1). 2017 SAGE open medicine Result HIV A98G;G190A;K101E;V90I 90;59;109;75 94;64;114;79 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. The only other NNRTI RAM that emerged in >=5 VFs was H221Y (6/49), which is not an etravirine RAM. 2017 SAGE open medicine Result HIV H221Y 53 58 NNRTI 15 20 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. All 37 children with L74V/I mutations also had M184V and thus high-level resistance to ABC from this combination of mutations. 2017 The Pediatric infectious disease journal Result HIV L74I;L74V;M184V 21;21;47 27;27;52 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. Detection of L74V/I was associated with ABC use (P < 0.001, 2-tailed Fisher's exact test) compared with those not on ABC (Table 1), but was not associated with the concurrent use of nevirapine , efavirenz or lopinavir/ritonavir (P = 0.34, P = 0.24 and P = 1.00, respectively, 2-tailed Fisher's exact test). 2017 The Pediatric infectious disease journal Result HIV L74I;L74V 13;13 19;19 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. Of the 121 children on any regimens with DRMs, 37 (31%) harbored L74V/I mutations with 35 (95%) being on ABC-containing regimens at the time of sample collection; for 32 of these children, ABC was part of their original ART regimens. 2017 The Pediatric infectious disease journal Result HIV L74I;L74V 65;65 71;71 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. Of the 35 children on ABC with L74V/I mutations, 30 had L74V, 4 had L74L/V and 1 had an L74I/V mixture. 2017 The Pediatric infectious disease journal Result HIV L74I;L74I;L74L;L74V;L74V;L74V;L74V 31;88;68;88;31;56;68 37;94;74;94;37;60;74 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. The mean duration of ART for children with L74V/I mutations was 750 days (range 140-1127). 2017 The Pediatric infectious disease journal Result HIV L74I;L74V 43;43 49;49 28383402 Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice. Of these, 25 (69%) had a K103N, 4 (11%) a K65R, 14 (39%) an M184 V/I, and 7 (19%) had a thymidine analog mutation. 2017 Medicine Result HIV K103N;K65R;M184I;M184V 25;42;60;60 30;46;68;68 28383402 Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice. While a trend was seen toward an increased likelihood of M184 V mutations in the MTR group (5 out of 7) compared with the STR group (9 out of 29), it did not reach statistical significance. 2017 Medicine Result HIV M184V 57 63 28468838 HIV-1 Tat potently stabilises Mdm2 and enhances viral replication. S166A mutation of Mdm2 interferes with its stabilisation and interaction with Tat. 2017 The Biochemical journal Result HIV S166A 0 5 Tat 78 81 28468838 HIV-1 Tat potently stabilises Mdm2 and enhances viral replication. The above results highlight the significance of S166 phosphorylation of Mdm2 because, in the presence of Tat, both Mdm2 stabilisation and the interaction of Mdm2 with Tat are compromised by the S166A mutation. 2017 The Biochemical journal Result HIV S166A 194 199 Tat;Tat 105;167 108;170 28468838 HIV-1 Tat potently stabilises Mdm2 and enhances viral replication. The effect of S166A mutation of Mdm2 on its interaction with HIV-1 Tat was also investigated. 2017 The Biochemical journal Result HIV S166A 14 19 Tat 67 70 28468838 HIV-1 Tat potently stabilises Mdm2 and enhances viral replication. The effect of S166A mutation on the stability of Mdm2 was investigated in the presence of HIV-1 Tat. 2017 The Biochemical journal Result HIV S166A 14 19 Tat 96 99 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Again, the acquisition of M184V/I was faster for large cluster as compared with small cluster lineages. 2017 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 26;26 33;33 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Although isolate 14637, belonging to cluster 185, selected for S153Y (Figure 5b), three subsequent dolutegravir selections using this isolate resulted in R263K as the sole mutation (B. 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;S153Y 154;63 159;68 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. As depicted in Figure5, dolutegravir selections, performed on large cluster viruses, led to rapid appearance of R263K (n = 6/8) or S153Y (n = 1/8) as dominant members of quasi-species within 6-8 weeks, while H51Y (n = 1/8) appeared by week 12 (Figure5). 2017 The Journal of antimicrobial chemotherapy Result HIV H51Y;R263K;S153Y 208;112;131 212;117;136 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. By week 24, the dominant virus coexpressed T66I (99.5%), R263K (98.7%) and E157Q (94.1%) (Figure6a). 2017 The Journal of antimicrobial chemotherapy Result HIV E157Q;R263K;T66I 75;57;43 80;62;47 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Cluster 185 isolates 14947 and 14637 harbouring R263K and S153Y at weeks 30 and 34, respectively, were grown in the absence of dolutegravir pressure for a subsequent 19 and 17 weeks, respectively (Figure4a and b). 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;S153Y 48;58 53;63 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Deep sequencing-based genotyping showed T66I selection occurred prior to R263K followed by E157Q, which may have compensated for the fitness compromise of R263K (Figure6a). 2017 The Journal of antimicrobial chemotherapy Result HIV E157Q;R263K;R263K;T66I 91;73;155;40 96;78;160;44 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Drug concentrations of both drugs could not be increased following the acquisition of R263K. 2017 The Journal of antimicrobial chemotherapy Result HIV R263K 86 91 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Drug dose escalations with lamivudine in large cluster variants were associated with the appearance at week 8 of M184V (isolate 14947) or M184I (isolates 14637, 14997 and 14637). 2017 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 138;113 143;118 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Dual selections with dolutegravir and lamivudine showed the appearance of resistance in only one large cluster isolate (14947) with the first appearance of R263K at week 8 preceding the acquisition of M184I/V and M184V at weeks 15 and 23, respectively (Figure4d). 2017 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V;M184V;R263K 201;201;213;156 208;208;218;161 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. In contrast, elvitegravir selections performed on singleton/small cluster viral lineages were delayed with the first appearance of T66I as a singlet mutation occurring at week 23 in only two of four small cluster strains (Figure4b). 2017 The Journal of antimicrobial chemotherapy Result HIV T66I 131 135 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. In general, viral outgrowth under dolutegravir pressure resulted in R263K, S153Y or H51Y as singlet mutations, representing the dominant quasi-species (>96%) at weeks 24-36 based on ultradeep sequencing. 2017 The Journal of antimicrobial chemotherapy Result HIV H51Y;R263K;S153Y 84;68;75 88;73;80 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Incremental increases in dolutegravir concentrations (beyond 10 nM) following acquisition of R263K, S153Y and H51Y mutations could not be attempted because the pressure on viral survival was too great based on weekly RT assays (Figures4c and). 2017 The Journal of antimicrobial chemotherapy Result HIV H51Y;R263K;S153Y 110;93;100 114;98;105 RT 217 219 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. INSTI-associated mutations were present at really low frequency as determined by deep sequencing (R263K at 1.1% and Y143H at 1.6% in 14514 and 14380, respectively) (Figure5c and d). 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;Y143H 98;116 104;121 INSTI 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Interestingly, culturing HIV-1 isolate 14947 (cluster 185) with dolutegravir led to the rapid selection of variants carrying the R263K mutation, as rapidly as M184V selection with lamivudine (Figure4a and d). 2017 The Journal of antimicrobial chemotherapy Result HIV M184V;R263K 159;129 164;134 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Isolate 10387 showed the dual appearance of R263K and S153F as 52% and 10.9% of the quasi-species at week 8, although R263K (99%) became and remained the dominant quasi-species at week 26 (Figure5d). 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;R263K;S153F 44;118;54 49;123;59 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Isolate 14947 acquired T66I and R263K within 8 weeks, representing 98.7% and 44.9% of the quasi-species, respectively (Figure6a). 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;T66I 32;23 37;27 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Isolate 14969 acquired S147G (92.1%) at week 8 followed by Q148R (99.7%), known to confer high levels of cross-resistance to elvitegravir and raltegravir (Figure7d). 2017 The Journal of antimicrobial chemotherapy Result HIV Q148R;S147G 59;23 64;28 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Isolate 14997 acquired a mixture of different viruses with T66I, E92G, E157Q, H51Y and/or S147G representing 85.9%, 19.8%, 99.7%, 15.0% and 9.9% of variants at week 36 (Figure6c). 2017 The Journal of antimicrobial chemotherapy Result HIV E157Q;E92G;H51Y;S147G;T66I 71;65;78;90;59 76;69;82;95;63 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. It is also significant that R263K arose more rapidly than M184V in dolutegravir + lamivudine dual selections performed with isolate 14947 and that both mutations can coexist (Figures4d and5i). 2017 The Journal of antimicrobial chemotherapy Result HIV M184V;R263K 58;28 63;33 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. It was rather surprising that R263K and H51Y did not adversely impact on viral replicative competence with elvitegravir as observed for dolutegravir (Figure6a). 2017 The Journal of antimicrobial chemotherapy Result HIV H51Y;R263K 40;30 44;35 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. It was, however, noteworthy that the acquisition of R263K and S153Y had a negative impact on RT enzymatic activity, hindering escalations in dolutegravir concentrations beyond 5-10 nM (Figure4c). 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;S153Y 52;62 57;67 RT 93 95 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Large cluster strains also showed a lower barrier to resistance to dolutegravir with R263K (n = 3) or S153Y (n = 1) mutations appearing by week 8 in large cluster lineages; these mutations were absent in the four small cluster viruses at week 36 (Figure 4c). 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;S153Y 85;102 90;107 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Large cluster variants showed a more rapid shift from M184I to M184V when compared with small cluster lineages where selection of M184I was attenuated. 2017 The Journal of antimicrobial chemotherapy Result HIV M184I;M184I;M184V 54;130;63 59;135;68 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Notably, isolate 5326 acquiring S153Y showed no further accumulation of mutations after 128 weeks of culture in the presence of dolutegravir (Figure5b). 2017 The Journal of antimicrobial chemotherapy Result HIV S153Y 32 37 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Similarly, elvitegravir drug selections performed on four large cluster variants progressed more rapidly, leading to the first acquisition of the INSTI resistance mutations T66I (n = 2), N155H (n = 1) or S147G (n = 1) at week 8, followed by the further accumulation of resistance mutations leading to viral escape (>100-fold resistance) at weeks 23 and 36 (Figure3b). 2017 The Journal of antimicrobial chemotherapy Result HIV N155H;S147G;T66I 187;204;173 192;209;177 INSTI 146 151 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Similarly, the acquisition of T66I followed by secondary mutations, including L74M, Q146K, and G163R, by small cluster viruses contributed to viral escape by week 24 (Figure7e and f). 2017 The Journal of antimicrobial chemotherapy Result HIV G163R;L74M;Q146K;T66I 95;78;84;30 100;82;89;34 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Small cluster isolates developed resistance more slowly, acquiring M184I infections by week 23 (Figure3a). 2017 The Journal of antimicrobial chemotherapy Result HIV M184I 67 72 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The infrequent appearance of S230R, E157Q, G163R or G59E minority species (<10%) occurred in some large cluster selections at selected weeks of passage but failed to accumulate over time. 2017 The Journal of antimicrobial chemotherapy Result HIV E157Q;G163R;G59E;S230R 36;43;52;29 41;48;56;34 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The latter isolates shifted from M184I to M184V by weeks 15-23, leading to higher fold resistance (>100-fold) and viral escape. 2017 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 33;42 38;47 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The M184I substitution conferred lower fold resistance, decreased processivity and replicative fitness than the M184V mutation. 2017 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 4;112 9;117 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The presence of secondary (accessory) mutations, including T66I, E157Q, G163R and S230R, can increase levels of resistance and/or viral fitness (Figures4b and). 2017 The Journal of antimicrobial chemotherapy Result HIV E157Q;G163R;S230R;T66I 65;72;82;59 70;77;87;63 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The rapid selection of M184V by isolate 14947 parallels that observed for CXCR4-tropic pNL4.3 reference strain grown in MT-2 cells or CBMCs. 2017 The Journal of antimicrobial chemotherapy Result HIV M184V 23 28 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The release of drug pressure failed to lead to a reversion of R263K or S153Y, substantiating their presence as dominant quasi-species. 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;S153Y 62;71 67;76 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The remaining two small clusters (cluster sizes 2 and 4) selected R263K or S153Y as singleton mutations (Figure5a and b). 2017 The Journal of antimicrobial chemotherapy Result HIV R263K;S153Y 66;75 71;80 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The second isolate, belonging to cluster 185 (14637), developed resistance with viruses coexpressing N155H (99.5%), Q95K (97.5%) and S230R (99.6%) as the dominant quasi-species (Figure6b). 2017 The Journal of antimicrobial chemotherapy Result HIV N155H;Q95K;S230R 101;116;133 106;120;138 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. In contrast, the protein levels of TatD60 and TatVT6 were detectable even after 3 h of treatment (Figures 3A,B) indicating that Ser46Phe and recombination events in TatD60 and TatVT6 respectively could possibly stabilize Tat protein. 2017 Frontiers in microbiology Result HIV S46F 128 136 Tat;Tat;Tat 35;165;221 38;168;224 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. In group 3 patients (n = 3), the mean viral loads was 265 copies/ml indicating that the patients in this mutation group 3 could be affected by the transactivation level caused due to Ser46Phe and other mutations in this group (particularly TatD60 is 346 copies/ml), however, there could be also multiple other factors might affect both the CD4 count and the viral load indicating the need for the further study in a large sample size (Supplementary Table S3). 2017 Frontiers in microbiology Result HIV S46F 183 191 Tat 240 243 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. In summary, the order of transactivation induced by variants TatD60 > TatV6 > TatN12 (Figure 1D) indicating Ser46Phe mutation play a significant role in transactivation, whereas, other natural mutations did not have a significant role on LTR transactivation. 2017 Frontiers in microbiology Result HIV S46F 108 116 LTR;Tat;Tat;Tat 238;61;70;78 241;64;73;81 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. In this study, CD4 counts were follow-up for 6 months for HIV-1 infected patients (n = 15) which included: group 1 was consisted of HIV-1 infected patients (n = 9) lacking Ser46Phe in Tat C; group 2 was consisted of HIV-1 infected patients (n = 3) lacking Ser46Phe in Tat B/C recombinant; and group 3 was consisted of HIV-1 infected patients (n = 3) with Ser46Phe and Ser61Arg in Tat C. 2017 Frontiers in microbiology Result HIV S46F;S46F;S46F;S61R 172;256;355;368 180;264;363;376 Tat;Tat;Tat 184;268;380 187;271;383 HIV infections;HIV infections;HIV infections;HIV infections 58;132;216;318 72;146;230;332 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. In wild-type TatC, Ser46 resulted in a single H-bond with TAR (occupancy ~71%) (Figure 5E), while the corresponding position was Phe46 in TatD60 resulting in one H-bond with TAR only transiently (occupancy below 1%); evidently, the single Ser46Phe mutation had a considerable effect on the H-bond profile of the TatD60-TAR complex (Figure 5F). 2017 Frontiers in microbiology Result HIV S46F 239 247 Tat;Tat 138;312 141;315 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. It is worth mentioning that Ser46Phe mutation is also reported from neighboring countries like Myanmar and China (HIV database)1; however, the functional implication of this mutation on Tat-TAR mediated transactivation has not been studied. 2017 Frontiers in microbiology Result HIV S46F 28 36 Tat 186 189 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Next, three Tat variants (TatN12, TatD60, and TatVT6) were selected based on their similarity in inducing LTR transactivation and carrying similar mutations (similar pattern of nucleotide changes) in the Tat gene (selected a variant from each group as a representative variant) for the TAR RNA interaction study which included TatN12, a subtype C variant (that lacked Ser46Phe) with Leu35Pro and Gly44Ser; TatD60, also a subtype C variant (with Ser46Phe) with Glu9Lys and Ser61Arg; and TatVT6, a B/C recombinant (that lacked Ser46Phe) (Figure 1B). 2017 Frontiers in microbiology Result HIV E9K;G44S;L35P;S46F;S46F;S46F;S61R 460;396;383;368;445;525;472 467;404;391;376;453;533;480 LTR;Tat;Tat;Tat;Tat;Tat;Tat 106;12;26;34;204;327;406 109;15;29;37;207;330;409 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Notably, the three variants (TatD60, TatE59, and TatE64 were used for transactivation study) and other variants (TatVT1, TatVT3, TatA7, TatN14, TatN17, TatCSW1, TatS5, TatS6) with Ser46Phe were clustered together in the phylogenetic tree indicating the proper classification of Tat variants into three different groups for the functional characterization. 2017 Frontiers in microbiology Result HIV S46F 180 188 Tat;Tat;Tat;Tat;Tat;Tat;Tat;Tat;Tat 29;37;49;129;136;144;161;168;278 32;40;52;132;139;147;164;171;281 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. TatD60 carrying Ser46Phe showed a significantly higher level of transactivation (P < 0.05) than wild-type Tat C as well as other variants. 2017 Frontiers in microbiology Result HIV S46F 16 24 Tat;Tat 0;106 3;109 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. TatN12 and TatVT6 were expressed at similar levels of protein expression when compared to wild-type Tat C; while TatD60 (Ser46Phe) resulted in an elevated level of expression (Figures 1E,F) suggesting that Ser46Phe and Ser61Arg mutations in TatD60 could affect Tat protein expression. 2017 Frontiers in microbiology Result HIV S46F;S46F;S61R 121;206;219 129;214;227 Tat;Tat;Tat;Tat;Tat 0;100;113;241;261 3;103;116;244;264 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. TatVT6 showed a slightly lower ubiquitination than wild-type TatC while TatD60 showed less ubiquitination indicating that Ser46Phe and Ser61Arg could stabilize Tat protein (Figures 4A,B), though it is not known if Ser46 and Ser61 are targets for ubiquitination. 2017 Frontiers in microbiology Result HIV S46F;S61R 122;135 130;143 Tat;Tat 72;160 75;163 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. The binding affinity of TatN12 to TAR was less than wild-type TatC-TAR complex but not significantly; whereas the TatD60 variant carrying Ser46Phe showed significantly higher (P < 0.05) binding affinity with TAR RNA (Figures 2A,B). 2017 Frontiers in microbiology Result HIV S46F 138 146 Tat;Tat 24;114 27;117 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. This reduction could be due to Ser46Phe mutation in TatD60 which created a conformational change in order to bind strongly with TAR ribonucleotides and produced a more stable TatD60-TAR complex. 2017 Frontiers in microbiology Result HIV S46F 31 39 Tat;Tat 52;175 55;178 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. This showed that the patients in this mutation group 3 could be affected due to Ser46Phe and other mutations in this group (Supplementary Table S3). 2017 Frontiers in microbiology Result HIV S46F 80 88 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. To determine whether Ser46Phe and other mutations play a role on Tat protein stability, a cycloheximide chase assay was performed. 2017 Frontiers in microbiology Result HIV S46F 21 29 Tat 65 68 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. Class 5 shows the most internal divergence with 4 mutations that peaked markedly in one year, whereas the remaining mutations are observed at uniformly low to moderate frequencies across all years, including the M36I mutation that stands out by virtue of its sustained moderate frequency level. 2017 PloS one Result HIV M36I 212 216 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The 3 most prevalent HIV-1 resistance-associated mutations for PRO were L63P (73.9%), V77I (45.2%) and I13V (34.2%), whereas I50L, I50V and K20I were the least abundant mutations recorded during the 10-year period (Figs 2 and 4). 2017 PloS one Result HIV I13V;I50L;I50V;K20I;L63P;V77I 103;125;131;140;72;86 107;129;135;144;76;90 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The RT mutations with the highest average frequencies were M184V (47.9%), K103N (42.6%) and M41L (34.2%) (Figs 2 and 5); the three least common RT mutations over the 10-year period were K103T, Y188C and P236L (S1 Table). 2017 PloS one Result HIV K103N;K103T;M184V;M41L;P236L;Y188C 74;186;59;92;203;193 79;191;64;96;208;198 RT;RT 4;144 6;146 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. One (0.97%) of the samples analyzed had only one NRTI mutation (T69N); two of the samples had three drug resistance mutations each, and shared a common NRTI mutation M184V. 2017 The open microbiology journal Result HIV M184V;T69N 166;64 171;68 NRTI;NRTI 49;152 53;156 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. One participant had seven mutations, three were TAMs (L210W, T215Y and M41L), two were NRTI mutations (M184V, V75I) and two were NNRTI mutations (G190A, V106M) (Table 4). 2017 The open microbiology journal Result HIV G190A;L210W;M184V;M41L;T215Y;V106M;V75I 146;54;103;71;61;153;110 151;59;108;75;66;158;114 NNRTI;NRTI 129;87 134;91 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. The most frequently occurring mutation in the whole group of patients was the M184V mutation, which occurred in five of the six (83%) participants who had mutations (Table 4). 2017 The open microbiology journal Result HIV M184V 78 83 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. The mutations observed were; NRTI mutations T69D, T69N, V75I and M184V; NNRTI mutations, K103N, V106M, Y181C and G190A; and TAMs (M41L, D67N, K70R, L210W, T215Y, K219Q) (Table 3). 2017 The open microbiology journal Result HIV D67N;G190A;K103N;K219Q;K70R;L210W;M184V;M41L;T215Y;T69D;T69N;V106M;V75I;Y181C 136;113;89;162;142;148;65;130;155;44;50;96;56;103 140;118;94;167;146;153;70;134;160;48;54;101;60;108 NNRTI;NRTI 72;29 77;33 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. 2) Six protease inhibitors (PIs) DRMs were observed including, four PIs accessory DRMs: L23I (n = 1), K43T (n = 1) and Q58E (n = 2); and two PIs major DRMs: M46I. 2017 PloS one Result HIV K43T;L23I;M46I;Q58E 102;88;157;119 106;92;161;123 PR;PI;PI;PI 7;28;68;141 15;31;71;144 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. 3) Two nucleotide reverse transcriptase inhibitors (NRTIs) DRMs were: K219R and K70Q. 2017 PloS one Result HIV K219R;K70Q 70;80 75;84 RT;NRTI 18;52 39;57 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. 31 specific DRMs were identified from 27 samples with DRMs distributing as: 1) 74.2% (23/31) DRMs were on nonnucleoside reverse transcriptase inhibitors (NNRTIs) as: V179E/D (n = 16), K238N (n = 2), E138A/G (n = 4) and G190E (n = 1). 2017 PloS one Result HIV E138A;E138G;G190E;K238N;V179D;V179E 199;199;219;184;166;166 206;206;224;189;173;173 NNRTI;NNRTI 106;154 141;160 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. For example, 16 of 27 donors showed PLLR (or above) to NNRTI due to V179D/E mutations; three donors with mutations of E138A were found to have PLLR to etravirine (ETR) and low-level resistance (LLR) to rilpivirine (RPV); specimen CQ12003214 was identified to have PLLR to five PIs and intermediate resistance (IR) to nelfinavir (NFV) caused by PI major DRM of M46I; two samples had PLLR to nelfinavir (NFV) and LLR to tipranavir (TPV) due to PI accessory DRM of Q58E; While one male donor (Specimen ID: LY12004233) from Luoyang with HIV recent infection bears high-level resistance (HLR) to efavirenz (EFV), nevirapine (NVP) and RPV and intermediate-level resistance (ILR) to ETR due to mutation of E138G and G190E. 2017 PloS one Result HIV E138A;E138G;G190E;M46I;Q58E;V179D;V179E 118;699;709;360;462;68;68 123;704;714;364;466;75;75 NNRTI;PI;PI;PI 55;277;344;442 60;280;346;444 HIV infections 533 553 28640909 HIV-Tat regulates macrophage gene expression in the context of neuroAIDS. We examined the role of lysine 50 of Tat in the regulation of the genes C5, CRLF2, APBA1, and BDNF by changing the Lysine 50 to alanine (K50ATat-Flag), and generated stable THP-1 mutant cell lines that express K50ATat-Flag (Fig 5A). 2017 PloS one Result HIV K50A 115 135 Tat 37 40 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The only major NNRTI mutation detected was K103N (n = 1; 0.9%), which causes high-level resistance to efavirenz (EFV) and nevirapine (NVP). 2017 Infection ecology & epidemiology Result HIV K103N 43 48 NNRTI 15 20 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The other NRTI mutation detected was M41L (n = 1; 0.9%), which causes intermediate resistance to AZT and d4T. 2017 Infection ecology & epidemiology Result HIV M41L 37 41 NRTI 10 14 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The patients within this cluster harboured T215C/D and were diagnosed between 1997 and 2008. 2017 Infection ecology & epidemiology Result HIV T215C;T215D 43;43 50;50 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The time to the most recent common ancestor of the cluster harbouring (T215C/D) dated back to 1989 (median estimate, 95% highest posterior density interval: 1983-1994). 2017 Infection ecology & epidemiology Result HIV T215C;T215D 71;71 78;78 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The two major PI mutations found were M46I (n = 1; 0.9%), which causes low-level resistance to nelfinavir (NFV) and L90M (n = 1; 0.9%), which causes high-level resistance to NFV, intermediate resistance to indinavir/ritonavir (IDV/r) and saquinavir/ritonavir (SQV/r) and low-level resistance to atazanavir/ritonavir (ATV/r), fosamprenavir/ritonavir (FPV/r) and lopinavir/ritonavir (LPV/r). 2017 Infection ecology & epidemiology Result HIV L90M;M46I 116;38 120;42 PI 14 16 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. Thymidine analogue 215 revertant mutants (T215C/D), that cause low-level resistance to azidothymidine (AZT) and stavudine (d4T), dominated the NRTI mutations detected (n = 7; 6%). 2017 Infection ecology & epidemiology Result HIV T215C;T215D 42;42 49;49 NRTI 143 147 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. 1b, c), rilpivirine resistance-associated mutations E138A followed by E138G and E138K accounted for more than 95% of reverse transcriptase codon 138 variants across HIV-1 subtypes A-G and CRFs 01_AE and 02_AG in the Stanford database (Supplemental Figure 1, http://links.lww.com/QAD/B122). 2017 AIDS (London, England) Result HIV E138A;E138G;E138K 52;70;80 57;75;85 RT 117 138 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. 4) strongly suggest that, once selected in HLA-B*18-positive individuals, E138X mutations are stably maintained even after transmission to HLA-B*18-negative individuals. 2017 AIDS (London, England) Result HIV E138X 74 79 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Although relative enrichment of E138A in HIV-1 subtype C compared with subtype B has previously been reported, reverse transcriptase-E138X distribution is incompletely characterized in other major HIV-1 subtypes though the data in. 2017 AIDS (London, England) Result HIV E138A;E138X 32;133 37;138 RT 111 132 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Analysis of linked viral/HLA genotypes from 7772 antiretroviral-naive HIV-infected patients from 16 cohorts spanning five continents revealed a highly significant overall enrichment of reverse transcriptase-E138X among HLA-B*18-positive compared with HLA-B*18-negative individuals, with 11.9 and 2.1% of B*18-positive and B*18-negative individuals, respectively, harbouring reverse transcriptase-E138X (P= 3.5 10-20. 2017 AIDS (London, England) Result HIV E138X;E138X 207;396 212;401 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Consistent with recent reports of population-level HIV-1 adaptation to HLA class I alleles in human populations, E138X prevalence correlated significantly with HLA-B*18 frequency in the 16 antiretroviral-naive study cohorts. 2017 AIDS (London, England) Result HIV E138X 113 118 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. E138X variants exhibited no significant differences in replicative kinetics with respect to wild-type HIV-1 in a 10-day monoculture assay. 2017 AIDS (London, England) Result HIV E138X 0 5 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. In the remaining 13 countries, E138X frequencies ranged from 5.6 to 21% in B*18-expressing persons compared with only 0.37-10% in non-B*18-expressing persons. 2017 AIDS (London, England) Result HIV E138X 31 36 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Moreover, the enrichment of reverse transcriptase-E138X variants in B*18-expressing persons was statistically significant in seven of these 13 countries (Japan, Mexico, Guatemala, South Africa, United States, Uganda, and Canada). 2017 AIDS (London, England) Result HIV E138X 50 55 RT 28 49 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Overall, these data strongly suggest that reverse transcriptase-E138X variants are accumulating in regions where the restricting HLA-B*18 allele is more common. 2017 AIDS (London, England) Result HIV E138X 64 69 RT 42 63 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X frequency in published HIV-1 reverse transcriptase sequences from Zimbabwe, for example, exceeds 15%. 2017 AIDS (London, England) Result HIV E138X 22 27 RT;RT 0;57 21;78 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X prevalence was also elevated in certain Southeastern European nations dominated by HIV-1 subtype F epidemics where B*18 frequency is also elevated (e.g. 2017 AIDS (London, England) Result HIV E138X 22 27 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138X was most common in subtype C (6.7%), followed by D (4.3%), A (3.9%), B (1.9%), and CRF01_AE (0.68%; all comparisons except CRF01_AE significant at P<0.05 with subtype B used as the reference group). 2017 AIDS (London, England) Result HIV E138X 22 27 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Stratified by cohort, E138X was enriched in B*18-expressing individuals in all countries except Belize (where no E138X variants were observed), Vietnam, and the United Kingdom (where overall E138X frequencies were <1%). 2017 AIDS (London, England) Result HIV E138X;E138X;E138X 22;113;191 27;118;196 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Strikingly, the areas where population reverse transcriptase-E138X frequencies are most elevated (e.g. 2017 AIDS (London, England) Result HIV E138X 61 66 RT 39 60 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. The lack of in-vitro replicative costs, combined with the significant positive correlation between reverse transcriptase-E138X and HLA-B*18 frequencies in all regions. 2017 AIDS (London, England) Result HIV E138X 121 126 RT 99 120 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. The most common variants at this position, comprising 97.6% of all those observed, were E138A, followed by E138G and E138K. 2017 AIDS (London, England) Result HIV E138A;E138G;E138K 88;107;117 93;112;122 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. The positive relationship between reverse transcriptase-E138X and B*18 population frequencies was further corroborated by an analysis of unlinked reverse transcriptase-E138X and HLA-B*18 data from 43 countries (see methods; Spearman's R = 0.34; P = 0.02. 2017 AIDS (London, England) Result HIV E138X;E138X 56;168 61;173 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. The relationship between HLA-B*18 carriage and reverse transcriptase-E138X frequency was also heretofore incompletely uncharacterized for non-B HIV-1 subtypes: but stratification of our 15 cohorts by HIV-1 subtype revealed statistically significant associations between E138X and HLA-B*18 carriage in HIV-1 subtypes B, C, and D, and a marginally significant association in CRF01_AE. 2017 AIDS (London, England) Result HIV E138X;E138X 69;270 74;275 RT 47 68 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. These observations confirm reproducible selection of reverse transcriptase-E138X by HLA-B*18 in human populations globally. 2017 AIDS (London, England) Result HIV E138X 75 80 RT 53 74 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. This remained true regardless of, whether E138X frequencies were computed in the overall population (Spearman's R = 0.75; P = 7.6 x 10-4. 2017 AIDS (London, England) Result HIV E138X 42 47 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. To assess the replicative cost of reverse transcriptase-E138X (as a surrogate of its potential to persist upon transmission) we constructed recombinant HIV-1 variants harbouring E138A, E138G, and E138K and assessed their in-vitro replicative competence compared with wild-type HIV-1 (E138). 2017 AIDS (London, England) Result HIV E138A;E138G;E138K;E138X 178;185;196;56 183;190;201;61 RT 34 55 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Together, these data indicate that regional reverse transcriptase-E138X prevalence depends on both HIV-1 subtype as well as population HLA-B*18 frequency. 2017 AIDS (London, England) Result HIV E138X 66 71 RT 44 65 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Visualization of reverse transcriptase-E138X distribution confirmed substantial frequency differences globally, with regions hardest hit by the epidemic, notably Sub-Saharan African nations where HIV-1 subtype C predominates, harbouring the highest reverse transcriptase-E138X burdens (Supplemental Figure 2, http://links.lww.com/QAD/B122). 2017 AIDS (London, England) Result HIV E138X;E138X 39;271 44;276 RT;RT 17;249 38;270 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. We, therefore, stratified reverse transcriptase-E138X prevalence by subtype in our 15 cohorts with linked HIV/HLA data. 2017 AIDS (London, England) Result HIV E138X 48 53 RT 26 47 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. Considering that the helix alpha6 is important for complex formation, we constructed a set of IN triple point mutants: IN_Q209A/E212A/L213A, IN_T206A/D207A/T210A and IN_K211A/K215A/K219A. 2017 Scientific reports Result HIV D207A;E212A;K211A;K215A;K219A;L213A;Q209A;T206A;T210A 150;128;169;175;181;134;122;144;156 155;133;174;180;186;139;127;149;161 IN;IN;IN;IN 94;119;141;166 96;121;143;168 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. For this purpose we used plasmid vectors for eukaryotic expression of wt IN (IN_WT) and IN containing both mutations E212A and L213A, preventing its binding with Ku70 in vitro (IN_Mut). 2017 Scientific reports Result HIV E212A;L213A 117;127 122;132 IN;IN 73;88 75;90 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. Importantly both IN_E212A and IN_L212A point mutants were also unable to form a complex with Ku70 as shown by a His6-pull down assay. 2017 Scientific reports Result HIV E212A;L212A 20;33 25;38 IN;IN 17;30 19;32 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. The Q209A substitution did not alter the complex formation between IN and Ku70_1-250 while both IN_E212A and IN_L213A lost their affinity for Ku70_1-250. 2017 Scientific reports Result HIV E212A;L213A;Q209A 99;112;4 104;117;9 IN;IN;IN 67;96;109 69;98;111 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. Triple mutants IN_T206A/D207A/T210A and IN_K211A/K215A/K219A retained their Ku70-binding activity while the mutant IN_Q209A/E212A/L213A was unable to form a detectable complex with Ku70_1-250. 2017 Scientific reports Result HIV D207A;E212A;K211A;K215A;K219A;L213A;Q209A;T206A;T210A 24;124;43;49;55;130;118;18;30 29;129;48;54;60;135;123;23;35 IN;IN;IN 15;40;115 17;42;117 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. A similar trend in WT and N74D virus integration preference was found for the group of genes related to cell metabolism (Fig 5B). 2017 PLoS pathogens Result HIV N74D 26 30 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Although there was integration preference above baseline in this group of genes, it was not as pronounced as for T-cell activation or metabolism genes and there was no difference between WT and N74D viruses (Fig 5C). 2017 PLoS pathogens Result HIV N74D 194 198 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. As expected, in the presence of raltegravir, infection by both WT and N74D viruses was reduced at 48h post-infection (S2H Fig) and was reduced much further 10 days post-infection (S2I Fig). 2017 PLoS pathogens Result HIV N74D 70 74 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Cluster analysis demonstrated a clear and significant distinction between treated and untreated samples but no significant distinction between cells infected with either WT or N74D viruses (S4 Fig). 2017 PLoS pathogens Result HIV N74D 176 180 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Conversely, if the N74D virus were less prone to integrate into genes perturbed by digoxin then this virus would be less susceptible to the drug. 2017 PLoS pathogens Result HIV N74D 19 23 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Digoxin increased N74D virus integration frequency within or near the T-cell activation genes although this did not reach statistical significance, presumably due to the lower number of integration sites that could be analysed (Fig 5A). 2017 PLoS pathogens Result HIV N74D 18 22 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Digoxin inhibited WT more than N74D virus whereas the integrase inhibitor raltegravir inhibited each virus equally (Fig 1B). 2017 PLoS pathogens Result HIV N74D 31 35 IN 54 63 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Digoxin inhibits infection by WT virus more potently than N74D virus. 2017 PLoS pathogens Result HIV N74D 58 62 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Digoxin inhibits viral gene expression (S2E-S2G Fig) and), yet the promoter/enhancer regions (LTR) of WT and N74D viruses were identical, excluding that the selectivity could be mediated by a direct effect of the drug on the LTR. 2017 PLoS pathogens Result HIV N74D 109 113 LTR;LTR 94;225 97;228 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Digoxin reduced WT virus integration near any gene and increased N74D virus integration near any gene (p < 0.001, Fisher's exact test) but this effect was quite small (Fig 4A). 2017 PLoS pathogens Result HIV N74D 65 69 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. HIV-1 WT has a greater preference to integrate within or near active genes than N74D virus and digoxin can trigger changes in cellular gene expression. 2017 PLoS pathogens Result HIV N74D 80 84 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. In agreement with our previous results, the N74D vector was less sensitive to digoxin relative to WT (S1B Fig). 2017 PLoS pathogens Result HIV N74D 44 48 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. In the absence of digoxin, WT and N74D HIV-1 LAIDeltaenv viruses showed similar infection levels (S1D Fig). 2017 PLoS pathogens Result HIV N74D 34 38 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. In the presence of digoxin, WT HIV-1 was inhibited more strongly than N74D at concentrations greater than 200 nM (Fig 1D and 1E), in agreement with the results in Jurkat cells. 2017 PLoS pathogens Result HIV N74D 70 74 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Jurkat CD4+ T-cells were co-infected with two VSV-G pseudotyped single cycle HIV-1 vectors, one containing WT CA and expressing GFP (WT-GFP), and another containing the CA N74D mutation and expressing mCherry (N74D-CHE). 2017 PLoS pathogens Result HIV N74D;N74D 172;210 176;214 Capsid;Capsid 110;169 112;171 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Jurkat cells, which express functional CD40L, were infected with HIV-1 LAIDeltaenv WT or N74D at an MOI ranging from 0.05 to 0.2 in the presence of different doses of an anti-CD40L neutralizing antibody. 2017 PLoS pathogens Result HIV N74D 89 93 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Nonetheless, irrespective of digoxin treatment, a significant gap remained between WT and N74D virus integration preference, which warranted further investigation. 2017 PLoS pathogens Result HIV N74D 90 94 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Notably, however, in contrast to the situation in the down-regulated genes, there was no WT/N74D selectivity for integration within up-regulated genes, there was a modest selectivity for integration near up-regulated genes and digoxin treatment enhanced the integration preference of each virus (Fig 4C). 2017 PLoS pathogens Result HIV N74D 92 96 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Notably, WT virus integrated more often than N74D virus within genes susceptible to down-regulation by digoxin ( 1.5 fold above baseline) (Fig 4B left panel), and this effect was stronger ( 2.5 fold above baseline) near such genes (Fig 4B right panel), demonstrating selectivity. 2017 PLoS pathogens Result HIV N74D 45 49 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Remarkably, the N74D virus was unaffected by the antibody (Fig 8E). 2017 PLoS pathogens Result HIV N74D 16 20 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Remarkably, WT virus had 23 hotspots and N74D virus had only one hotspot (in the RAG2 gene) (Fig 6). 2017 PLoS pathogens Result HIV N74D 41 45 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. The identification of Na+/K+ ATPase as the digoxin target did not readily explain preferential inhibition of WT over N74D virus. 2017 PLoS pathogens Result HIV N74D 117 121 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. The N74D virus integration preference within this gene group was similar to baseline whereas integration near these genes was 2-fold above baseline (Fig 5A). 2017 PLoS pathogens Result HIV N74D 4 8 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. The rationale for this assay was based on the different usage of host cell factors by WT and N74D viruses: selective hits were likely to target either the WT CA protein itself or host cell factors interacting preferentially with WT over N74D virus, directly or indirectly. 2017 PLoS pathogens Result HIV N74D;N74D 93;237 97;241 Capsid 158 160 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. There was a clear correlation between gene expression and integration frequency for both WT and N74D viruses, however we detected selectivity in the most highly expressed gene group: WT virus integrated into such genes more frequently than N74D virus (Fig 7C), which is in agreement with a recent report. 2017 PLoS pathogens Result HIV N74D;N74D 96;240 100;244 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Therefore, although a total of only 132 genes were analysed in the T-cell activation and cell metabolism pathways, WT virus integration within or near these genes was disproportionally frequent both in absolute terms and relative to the N74D virus. 2017 PLoS pathogens Result HIV N74D 237 241 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. These results support the link between differential sensitivity to digoxin of WT and N74D viruses and their different integration preference. 2017 PLoS pathogens Result HIV N74D 85 89 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. This difference between WT and N74D virus was large enough to suggest biological relevance. 2017 PLoS pathogens Result HIV N74D 31 35 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. This result supported the notion that WT selectively integrates within specific gene pathways and that this selectivity is lost for the N74D virus. 2017 PLoS pathogens Result HIV N74D 136 140 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Thus digoxin caused modest, albeit selective, changes in the integration preference of HIV-1 WT and N74D virus. 2017 PLoS pathogens Result HIV N74D 100 104 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Thus WT virus integrates more frequently than N74D virus within or near the most highly expressed genes; genes susceptible to down regulation by digoxin are amongst the most highly expressed hence WT virus integrates into such genes more frequently than N74D virus. 2017 PLoS pathogens Result HIV N74D;N74D 46;254 50;258 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. To confirm our screening results, we re-examined the selectivity of digoxin in single cycle infectious assays using WT-GFP or N74D-CHE HIV-1 vectors. 2017 PLoS pathogens Result HIV N74D 126 130 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. To control that the observed phenotype did not depend on the specific fluorescent marker expressed by each vector (GFP or CHE), we reversed the markers and infected Jurkat cells with WT-CHE and N74D-GFP vectors. 2017 PLoS pathogens Result HIV N74D 194 198 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. To test this hypothesis we carried out, in parallel, global gene expression and integration site analysis on cells that were infected with WT or N74D HIV-1 in the presence of digoxin or DMSO. 2017 PLoS pathogens Result HIV N74D 145 149 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. To test this notion further, we looked for integration hotspots of WT or N74D viruses in our samples. 2017 PLoS pathogens Result HIV N74D 73 77 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. To this end, a titration was performed on the luciferase Jurkat reporter cell line (1G5 cells) using HIV-1 NL4.3 WT or N74D, which showed that WT NL4.3 replicated marginally better than NL4.3 N74D (S1C Fig). 2017 PLoS pathogens Result HIV N74D 119 123 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. To validate the hypothesis that the selectivity of digoxin occurs at the integration stage, we examined the integration profile of single cycle WT and N74D HIV-1 LAIDeltaenv in digoxin-treated and untreated Jurkat cells. 2017 PLoS pathogens Result HIV N74D 151 155 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Transfection of Jurkat cells is extremely inefficient hence to test if the selective phenotype of digoxin was maintained in the absence of integration, we titrated digoxin in Jurkat cells pre-exposed to a high dose (20muM) of raltegravir (a potent integration inhibitor) and infected them with WT or N74D HIV-1 LAIDeltaenv (S2H Fig). 2017 PLoS pathogens Result HIV N74D 300 304 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. We aimed to identify small compounds that inhibited WT virus infection at least 50% of control (DMSO) with little inhibition of N74D virus infection ("selective hits"). 2017 PLoS pathogens Result HIV N74D 128 132 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. We conducted three independent experiments in Jurkat cells infected with WT or N74D LAIDeltaenv, ensuring that infection levels were within the linear range (S1E Fig), and extracted total RNA and DNA from each sample 36h post-infection (S3 Fig). 2017 PLoS pathogens Result HIV N74D 79 83 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. We correlated gene expression levels with frequency of integration for WT and N74D viruses. 2017 PLoS pathogens Result HIV N74D 78 82 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. We detected eighteen selective hits belonging to different chemical and pharmacological classes (S1 File and S1 Table): four were anti-inflammatory, hinting that WT and N74D virus may be differentially susceptible to innate immune responses and two were cardiac glycosides sharing a similar chemical structure: digoxin and digitoxin. 2017 PLoS pathogens Result HIV N74D 169 173 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. WT and N74D viruses also integrated more often than matched random control within or near genes susceptible to up-regulation by digoxin (Fig 4C). 2017 PLoS pathogens Result HIV N74D 7 11 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. WT and N74D viruses integrated preferentially within any gene, however WT virus favoured integration within any gene more strongly than the N74D virus relative to the expected random distribution (baseline) (Fig 4A left panel and S5B Fig). 2017 PLoS pathogens Result HIV N74D;N74D 7;140 11;144 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. WT virus had a clear preference ( 2 fold above baseline) to integrate near any gene (10 Kb from the transcriptional start site) whereas N74D virus did not (Fig 4A right panel), in agreement with previous observations. 2017 PLoS pathogens Result HIV N74D 136 140 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. 3C), while S75X and p17R76G displayed a molecular weight 10 and 170 fold higher than refp17. 2017 Scientific reports Result HIV S75X 11 15 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. 4A, refp17 inhibited the colony-forming ability of Raji B cells as compared to untreated cultures, while S75X and p17R76G enhanced their clonogenic activity. 2017 Scientific reports Result HIV S75X 105 109 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. 4B, Raji cells stimulated with refp17 showed a significant Akt inhibition, as expected, while S75X and p17R76G phosphorylated Akt kinase. 2017 Scientific reports Result HIV S75X 94 98 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. 4C and D, cells treated with S75X and p17R76G showed an increased PTEN phosphorylation as compared to unstimulated cells, whereas treatment of cells with refp17 resulted in a reduced PTEN phosphorylation level. 2017 Scientific reports Result HIV S75X 29 33 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. 5, S75X and p17R76G trigger the PI3K/Akt signaling pathway, which in turn could activate MAPK8 and YWHAZ, thus creating a positive feedback loop further strengthening Akt activation. 2017 Scientific reports Result HIV S75X 3 7 PI 32 34 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. A greater stability of H5 is observed in S75X and p17R76G as compared to refp17. 2017 Scientific reports Result HIV S75X 41 45 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. All these results suggest that S75X and p17R76G are less structured as compared to refp17. 2017 Scientific reports Result HIV S75X 31 35 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. However, S75X and p17R76G were noticeably less helical than refp17, as indicated by the reduction in ellipticity, suggesting a partial unfold of proteins. 2017 Scientific reports Result HIV S75X 9 13 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. In addition, the MD frames of p17s were clustered (% of the frames): two clusters (42% and 43%) in refp17, five clusters (29%, 26%, 15%, 9% and 7%) in the S75X and three clusters (25%, 23% and 22%) in p17R76G were obtained. 2017 Scientific reports Result HIV S75X 155 159 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. In addition, using the DSSP software and calculating the average of helix propensities of each aa along the trajectory, we assessed whether mutations in S75X and p17R76G induce any changes in secondary structure. 2017 Scientific reports Result HIV S75X 153 157 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. In order to confirm conformational shifts evidenced by MD, the structural conformation of refp17, S75X and p17R76G was investigated. 2017 Scientific reports Result HIV S75X 98 102 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. In order to evaluate the impact of mutations on protein structure, we subjected refp17, S75X and p17R76G to heat-induced denaturation and monitored them at 222 nm by CD spectroscopy. 2017 Scientific reports Result HIV S75X 88 92 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. In S75X the residue R76 results mutated in a G and this aa substitution leads to the loss of the E73-R76 hydrogen bond. 2017 Scientific reports Result HIV S75X 3 7 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Interestingly, S75X and p17R76G showed a disorganization in the N-terminal region of H3 and H4, and in the C-terminal region of H3. 2017 Scientific reports Result HIV S75X 15 19 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. On the contrary, S75X and p17R76G showed very few amide-amide NOE signals in the same region of the spectrum, consistent with dampened signals arising from the formation of soluble aggregates. 2017 Scientific reports Result HIV S75X 17 21 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Overall, our data suggest that a single R76G mutation in refp17 backbone can destabilize the viral protein with a reduction of alpha-helical secondary structures, thermal stability and soluble aggregates formation. 2017 Scientific reports Result HIV R76G 40 44 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Overall, these data show that p17R76G, like S75X, activates the proliferative PI3K/Akt pathway in B cells through PTEN down-modulation. 2017 Scientific reports Result HIV S75X 44 48 PI 78 80 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Overall, these findings show that changes in the hydrogen bond network, due to the insurgence of even a single point mutation (R76G), are responsible for changes in the secondary structure of refp17. 2017 Scientific reports Result HIV R76G 127 131 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Refp17 showed a higher stability than S75X and p17R76G, exhibiting a higher average number of hydrogen bonds (58 versus 48.5 and 55, respectively) and lower nonpolar surface areas (31.3% versus 33, 87% and 34, 23%, respectively). 2017 Scientific reports Result HIV S75X 38 42 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Refp17 was shown to enhance PTEN activity and down-modulate the PI3K/Akt signaling pathway, exerting an anti-proliferative effect on B cells, while S75X was shown to block PTEN and activate Akt, thus promoting B-cell growth. 2017 Scientific reports Result HIV S75X 148 152 PI 64 66 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. S75X and p17R76G activate the PTEN/PI3K/Akt pathway in B cells. 2017 Scientific reports Result HIV S75X 0 4 PI 35 37 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. S75X and p17R76G had similar Tm values, approximately 10 C lower than refp17 (Table 1). 2017 Scientific reports Result HIV S75X 0 4 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. S75X and p17R76G modulate different signaling molecules involved in cell cycle regulation. 2017 Scientific reports Result HIV S75X 0 4 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. S75X and p17R76G promote B-cell growth. 2017 Scientific reports Result HIV S75X 0 4 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Side chains of mutated residues in S75X and involved in hydrogen bonds are shown in. 2017 Scientific reports Result HIV S75X 35 39 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Since mutated residues in S75X. 2017 Scientific reports Result HIV S75X 26 30 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The dispersion indices were 12.39, 31.65 and 20.00 for refp17, S75X and p17R76G, respectively. 2017 Scientific reports Result HIV S75X 63 67 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The lysates of Raji cells, stimulated or not with refp17, p17R76G or S75X (0.1 mug/ml) were processed by Kinexus Bioinformatics Corporation for Kinex KAM-850 Antibody Microarray. 2017 Scientific reports Result HIV S75X 69 73 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The R76G mutation destabilizes refp17 and alters its ability to oligomerize in solution. 2017 Scientific reports Result HIV R76G 4 8 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The R76G mutation in the refp17 backbone induces changes in the protein secondary structure and hydrogen bond network. 2017 Scientific reports Result HIV R76G 4 8 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The signals relative to the 23 proteins modulated by S75X and p17R76G, verified by densitometric analysis and normalized to refp17, are reported in Table 2. 2017 Scientific reports Result HIV S75X 53 57 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The stability of H5 in S75X is due to the formation of the new hydrogen bond R91-E106 and in p17R76G of the R58-Q108 and Y86-E107 bonds. 2017 Scientific reports Result HIV S75X 23 27 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The stability of refp17, S75X and p17R76G was defined on the basis of these conditions along the dynamics: the total energy less than -40000 kcal/mol, RMSD of the structure in a range of 1 Angstrom around the centre of oscillations, the formation of hydrogen bonds, and the size of nonpolar surface area. 2017 Scientific reports Result HIV S75X 25 29 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Then, in order to rule out false positive array signals, all the protein modulated by S75X and p17R76G were confirmed by a multi-immunoblotting analysis performed by Kinexus. 2017 Scientific reports Result HIV S75X 86 90 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Therefore, in order to investigate the role of this hydrogen bond in the stability and folding of the matrix protein, we modeled S75X and p17R76G, a p17 mutant with R76 replaced by a G, and performed long MD (500 ns). 2017 Scientific reports Result HIV S75X 129 133 Matrix 102 108 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. These data highlight that the activation of PI3K/Akt pathway in B cells by clonogenic S75X and p17R76G can orchestrate the function of several molecules involved in promoting tumor survival and proliferation. 2017 Scientific reports Result HIV S75X 86 90 PI 44 46 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. These data suggest that a single aa mutation occurring in the refp17 backbone can induce a massive self-association, indicating that some refp17 buried hydrophobic residues become exposed in S75X and p17R76G. 2017 Scientific reports Result HIV S75X 191 195 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. These results confirm that the rupture of the E73-R76 hydrogen bond generates significant structural changes conferring to the matrix protein a S75X-like B-cell clonogenic activity. 2017 Scientific reports Result HIV S75X 144 148 Matrix 127 133 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. To further investigate the intracellular mechanisms involved in the B-cell growth-promoting activity of S75X and p17R76G, we assessed how these proteins modulate intracellular phosphorylations by employing a high-throughput antibody array technology. 2017 Scientific reports Result HIV S75X 104 108 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. we aimed at determining whether p17R76G, a mutant bearing a G at position 76 instead of an R, as in S75X, could acquire a B-cell clonogenic activity. 2017 Scientific reports Result HIV S75X 100 104 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. We performed in silico studies to elucidate if aa mutations in S75X were responsible for changes in folding and stability of the viral protein as compared to refp17. 2017 Scientific reports Result HIV S75X 63 67 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. A71T, A71AT, A71AV, L10I are PI minor resistance mutations. 2017 PloS one Result HIV A71A;A71A;A71T;A71V;L10I;A71T 6;13;6;13;20;0 11;18;11;18;24;4 PI 29 31 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. Additionally, the PIs drug resistance mutations I54V and V82A were identified for the first time in Shandong Province. 2017 PloS one Result HIV I54V;V82A 48;57 52;61 PI 18 21 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. In the mutations identified at time of diagnosis, A71T, A71AT, A71AV, V179D, V106I, V106EIKV are polymorphic mutations. 2017 PloS one Result HIV A71A;A71A;A71T;A71T;A71V;V106E;V106I;V106I;V106K;V106V;V179D 56;63;56;50;63;84;84;77;84;84;70 61;68;61;54;68;92;92;82;92;92;75 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. V108A is a highly unusual mutation at the position of 108, where usually is V108I, a non-polymorphic accessory mutation. 2017 PloS one Result HIV V108I;V108A 76;0 81;5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. We found that M184V and Y181C were also the most frequent point mutations in these patients. 2017 PloS one Result HIV M184V;Y181C 14;24 19;29 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. We found that M184V was the most frequent point mutation conferring resistance against NRTIs, whereas Y181C, G190A, K103N and V179D/E/F were the most frequent point mutations conferring resistance to NNRTIs. 2017 PloS one Result HIV G190A;K103N;M184V;V179D;V179E;V179F;Y181C 109;116;14;126;126;126;102 114;121;19;135;135;135;107 NNRTI;NRTI 200;87 206;92 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. 1) DRM were present, always in combination with Y181C. 2017 AIDS research and therapy Result HIV Y181C 48 53 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. A62V often occurs in combination with multi-resistance NRTI mutations K65R and Q151M. 2017 AIDS research and therapy Result HIV K65R;Q151M;A62V 70;79;0 74;84;4 NRTI 55 59 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Although H221Y has minimal detectable effect on NNRTI susceptibility, it has been found to frequently occur in combination with Y181C in RPV exposed patients. 2017 AIDS research and therapy Result HIV H221Y;Y181C 9;128 14;133 NNRTI 48 53 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Among EFV exposed patients, a relatively high prevalence of P225H (12.1%), was found in combination with K103N, confirming previous observations that this mutation rarely occurs independently. 2017 AIDS research and therapy Result HIV K103N;P225H 105;60 110;65 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. E138A/K/Q, a mutation related to the NNRTIs etravirine (ETR) and rilpivirine (RPV) was found in 8.6% of subjects, although these drugs are not currently available and not part of the standard treatment regimen in South Africa. 2017 AIDS research and therapy Result HIV E138A;E138K;E138Q 0;0;0 9;9;9 NNRTI 37 43 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Exceptionally, the M184V mutation prevalence in rural Limpopo was more closely related to urban Pretoria (51.7% vs. 2017 AIDS research and therapy Result HIV M184V 19 24 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Excluding E138A/K/Q among NNRTI mutations reduced the NNRTI resistance prevalence from 65.2 to 62.5%. 2017 AIDS research and therapy Result HIV E138A;E138K;E138Q 10;10;10 19;19;19 NNRTI;NNRTI 26;54 31;59 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. For the NNRTIs, one or two DRM (either K103N, V106M or G190A) were the most common and were more prevalent in subjects that had been on treatment for >5 years (p < 0.05. 2017 AIDS research and therapy Result HIV G190A;K103N;V106M 55;39;46 60;44;51 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Four cases of the H221Y (7%. 2017 AIDS research and therapy Result HIV H221Y 18 23 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. However, in the present study H221Y was identified only in patients with EFV exposure. 2017 AIDS research and therapy Result HIV H221Y 30 35 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. In this study, all the A62V mutations described were linked to K65R, but not to Q151M. 2017 AIDS research and therapy Result HIV A62V;K65R;Q151M 23;63;80 27;67;85 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Interestingly, among the viruses with mutations at this position, tyrosine (Y) was the dominant amino acid (6.9%; T215Y) compared to the complete absence of phenylalanine (F) (0%; T215F. 2017 AIDS research and therapy Result HIV T215F;T215Y 180;114 185;119 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Interestingly, four DRM were detected in a greater proportion of the population using the DNA assay, of which three were TAMs; namely D67N, K70R and K219Q/R/E. 2017 AIDS research and therapy Result HIV D67N;K219E;K219Q;K219R;K70R 134;149;149;149;140 138;158;158;158;144 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. M230L which causes high level resistance to the entire NNRTI class, occurred in a single case. 2017 AIDS research and therapy Result HIV M230L 0 5 NNRTI 55 60 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. More than half of these mutations (K65R, D67N, K70R, L74V, V75I/S, Y115F, K219Q/E, K101E/P/H, K103N, V106AM, Y181C and Y188L/H) were significantly more prevalent (p < 0.05) in the rural settings of Limpopo than in urban Pretoria (Table 2). 2017 AIDS research and therapy Result HIV D67N;K101E;K101H;K101P;K103N;K219E;K219Q;K65R;K70R;L74V;V106A;V106M;V75I;V75S;Y115F;Y181C;Y188H;Y188L 41;83;83;83;94;74;74;35;47;53;101;101;59;59;67;109;119;119 45;92;92;92;99;81;81;39;51;57;107;107;65;65;72;114;126;126 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Out of the five patients who carried multiple thymidine analogue mutations (TAMs) only one had the K65R mutation, suggesting that these TAMs likely resulted from previous AZT or d4T treatment and not exposure to TDF. 2017 AIDS research and therapy Result HIV K65R 99 103 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. T74S, a minor PR mutation, was detected in 45 (65.2%) of the 69 participants. 2017 AIDS research and therapy Result HIV T74S 0 4 PR 14 16 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. TAMs were dominated by D67N (13.8%), followed by K219Q/E (12.1%) and K70R (12.1%) with a low occurrence of T215Y/F (6.9%). 2017 AIDS research and therapy Result HIV D67N;K219E;K219Q;K70R;T215F;T215Y 23;49;49;69;107;107 27;56;56;73;114;114 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The 215I mutation seems to be transitional (intermediate) to T215F (phenylalanine-TTT, TTC). 2017 AIDS research and therapy Result HIV T215F 61 66 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The exception was the K103N mutation which was significantly more prevalent (p < 0.05) in assays of proviral DNA compared to assays using viral RNA. 2017 AIDS research and therapy Result HIV K103N 22 27 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The most dominant DRM against the reverse transcriptase inhibitors (RTI), were M184V (51.7%), K103N (50%), V106AM (20.6%), G190A (13.8%), D67N (13.8%), K65R (12.1%) and K219Q/E (12.1%. 2017 AIDS research and therapy Result HIV D67N;G190A;K103N;K219E;K219Q;K65R;M184V;V106A;V106M 138;123;94;169;169;152;79;107;107 142;128;99;176;176;156;84;113;113 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The Q151M multi-drug resistant mutation was found in one subject while the transitional mutation (Q151L) which precedes the emergence of Q151M was observed in 2 patients. 2017 AIDS research and therapy Result HIV Q151L;Q151M;Q151M 98;4;137 103;9;142 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The T215Y/F mutation seem to be subtype specific as it was recently found as the dominant TAM in 33.6% of non-subtype C infected study subjects in five Central African countries. 2017 AIDS research and therapy Result HIV T215F;T215Y 4;4 11;11 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Three subjects carried the accessory mutation A62V that has been reported to be widespread among subtype A viruses from countries of the former Soviet Union. 2017 AIDS research and therapy Result HIV A62V 46 50 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Two (3.0%) subjects harbored major PI DRM (D30N, M46I and V32I). 2017 AIDS research and therapy Result HIV D30N;M46I;V32I 43;49;58 47;53;62 PI 35 37 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Both had K65R TDRM, known to be associated with reduced replicative capacity, and were infected with subtype C virus, supporting the hypothesis that this mutation can develop more easily in subtype C than in other subtypes. 2017 Journal of the International AIDS Society Result HIV K65R 9 13 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Few polymorphic resistance mutations were identified by both NGS and SBS, e.g., V179D and different substitutions of the NNRTI DRM E138 amino acid. 2017 Journal of the International AIDS Society Result HIV V179D 80 85 NNRTI 121 126 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. However, since F77L is a transition mutation located within a homopolymeric region, a mutation that was also observed at a frequency below the quality assurance threshold (<1%) in 25% (18/72) of all other samples, we considered it a technical artefact of the PCR and sequencing procedures. 2017 Journal of the International AIDS Society Result HIV F77L 15 19 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. K65R is known to reduce the activity of both abacavir and lamivudine, while increasing susceptibility to zidovudine. 2017 Journal of the International AIDS Society Result HIV K65R 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. M184V (identified as minor variant in two patients) and T215S were the only highly prevalent NGS and SBS NRTI TDRM identified. 2017 Journal of the International AIDS Society Result HIV T215S;M184V 56;0 61;5 NRTI 105 109 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. M46I/L, potentially conferring low-level resistance to any PI, was the only mutation found in 5% (4/80) of the patients. 2017 Journal of the International AIDS Society Result HIV M46L;M46I 0;0 6;6 PI 59 61 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Mainly, E138A predicted to mostly affect rilpivirine resistance, was identified in three patients (infected with subtype A, AG and C) by both sequencing platforms (Figure 1). 2017 Journal of the International AIDS Society Result HIV E138A 8 13 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Patient 26,203, harbouring K65R (1.5%), was treated with trizivir (abacavir, lamivudine and zidovudine) 5 years after initial diagnosis. 2017 Journal of the International AIDS Society Result HIV K65R 27 31 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Patient 63,729, with the K65R mutation (2.5%) was successfully treated with truvada (TDF, emtricitabine and tenofovir disoproxil fumarate) and dolutegravir (DTG), a combined therapy that was initiated 3.7 years after the initial diagnosis. 2017 Journal of the International AIDS Society Result HIV K65R 25 29 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Some of the low-frequency TDRMs identified are consistent with APOBEC-mediated G-to-A editing: the PI M46L/I and D30N, the NRTI D67N and the NNRTI G190E TDRM, as well as the E138K amino substitution, were all related to APOBEC. 2017 Journal of the International AIDS Society Result HIV D30N;D67N;E138K;G190E;M46I;M46L 113;128;174;147;102;102 117;132;179;152;108;108 NNRTI;NRTI;PI 141;123;99 146;127;101 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. The NRTI TDRM identified at low frequency by NGS (<10% of the viral population), were D67N, K65R, and K70E, as well as F77L, which was the most frequent (8 patient samples) low-abundance (1.5-5%) NRTI TDRM identified. 2017 Journal of the International AIDS Society Result HIV D67N;F77L;K65R;K70E 86;119;92;102 90;123;96;106 NRTI;NRTI 4;196 8;200 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. While G190E and Y188C were minor NNRTI TDRM identified by NGS, K101E and K103N were identified by both NGS and SBS. 2017 Journal of the International AIDS Society Result HIV G190E;K101E;K103N;Y188C 6;63;73;16 11;68;78;21 NNRTI 33 38 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. In order to check the effect of additional mutations Glu9Lys and Ser61Arg in TatD60, docking was performed in comparison to wild type Tat C. 2017 Frontiers in microbiology Result HIV E9K;S61R 53;65 60;73 Tat;Tat 77;134 80;137 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. Mutation Ser61Arg results in more compact binding of TAR as Arg61 is making a hydrogen bond with C19 and A20 of TAR, suggest that Ser61Arg may have also a critical role in higher binding affinity of Tat and TAR binding. 2017 Frontiers in microbiology Result HIV S61R;S61R 9;130 17;138 Tat 199 202 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. TatD60 (Ser46Phe) showed relatively higher binding to TAR than TatC and other Tat variants. 2017 Frontiers in microbiology Result HIV S46F 8 16 Tat;Tat 0;78 3;81 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. TatN12 (subtype C) has Leu35Pro and Gly44Ser mutations but lacked Ser46Phe, TatD60 (subtype C) has Glu9Lys, Ser46Phe and Ser61Arg mutations, and TatVT6 is a B/C recombinant but lacked Ser46Phe. 2017 Frontiers in microbiology Result HIV E9K;G44S;L35P;S46F;S46F;S46F;S61R 99;36;23;66;108;184;121 106;44;31;74;116;192;129 Tat;Tat 0;76 3;79 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. Two mutations Leu35Pro and Gly44Ser in TatN12 appear to change the orientation of Arg49 residue which is essential for TAR interaction and transactivation. 2017 Frontiers in microbiology Result HIV G44S;L35P 27;14 35;22 Tat 39 42 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). All 3 participants developed M184V/I in RT. 2017 HIV clinical trials Result HIV M184I;M184V 29;29 36;36 RT 40 42 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). At a 15% cutoff, 10 participants had T97A (EVG/COBI/FTC/TDF: 9 of 288, 3.1%; ATV+RTV+FTC/TDF: 1 of 21, 4.8%), and at a 2% cutoff, 11 participants had T97A (EVG/COBI/FTC/TDF: 10 of 288, 3.5%; ATV+RTV+FTC/TDF: 1 of 21, 4.8%) by deep sequencing, at percentages ranging from 6.1% to 99.8%. 2017 HIV clinical trials Result HIV T97A;T97A 37;150 41;154 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). At a 2% cutoff, E92G and N155H were observed in 1 participant each, and S147G was observed in 2 participants, at low percentages ranging from 2.1% to 3.7% (mutational viral loads: E92G, 920 copies/mL; S147G, 430 copies/mL and 490 copies/mL; N155H, 770 copies/mL). 2017 HIV clinical trials Result HIV E92G;E92G;N155H;N155H;S147G;S147G 16;180;25;241;72;201 20;184;30;246;77;206 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Baseline samples from the 10 participants with T97A at >=15% (9 EVG/COBI/FTC/TDF; 1 ATV+RTV+FTC/TDF) were sent for population sequencing using the GeneSeq IN assay, and the presence of T97A was confirmed. 2017 HIV clinical trials Result HIV T97A;T97A 47;186 51;190 IN 156 158 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Consistent with these enrollment criteria, no participant had K65R or M184V/I RT substitutions at study entry. 2017 HIV clinical trials Result HIV K65R;M184I;M184V 62;70;70 66;77;77 RT 78 80 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Four other EVG/COBI/FTC/TDF participants had primary IN resistance substitutions (2 with S147G, 1 with E92G, 1 with N155H) present at low percentages ranging from 2.1% to 3.7%, and all four of these participants were virologic successes at Week 48. 2017 HIV clinical trials Result HIV E92G;N155H;S147G 103;116;89 107;121;94 IN 53 55 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Four participants (4 of 309, 1.3%) had the exclusion mutation M184I at baseline by deep sequencing at frequencies ranging from 2.0% to 9.7% (mutational viral loads of 44 copies/mL, 620 copies/mL, 2020 copies/mL, and 10590 copies/mL). 2017 HIV clinical trials Result HIV M184I 62 67 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). In addition, 4 participants had the exclusion mutation M184I at low levels by deep sequencing, and 3 of these participants were virologic successes at Week 48, and one participant was lost to follow up with the last available HIV-1 RNA <50 copies/mL. 2017 HIV clinical trials Result HIV M184I 55 60 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Of the two participants with T97A that were treated with ATV+RTV+FTC/TDF, one had <50 copies/mL HIV-1 RNA at Week 48, and one had >=50 copies/mL at Week 48. 2017 HIV clinical trials Result HIV T97A 29 33 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). One participant developed the NNRTI resistance substitution A98A/G, but this participant resuppressed HIV-1 RNA to <50 copies/mL while on study drugs. 2017 HIV clinical trials Result HIV A98A;A98G 60;60 66;66 NNRTI 30 35 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). One participant developed the NRTI resistance substitution D67D/N, but remained phenotypically susceptible to all drugs in their regimen. 2017 HIV clinical trials Result HIV D67D;D67N 59;59 65;65 NRTI 30 34 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). One participant had an M184M/I/V mixture and showed a 2.1-fold change in susceptibility to FTC, which is below the biological cutoff of the PhenoSense GT assay for FTC. 2017 HIV clinical trials Result HIV M184I;M184M;M184V 23;23;23 32;32;32 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). One participant treated with EVG/COBI/FTC/TDF had the NNRTI substitution K101E present at 23.1% in their failure sample; this mutation was not detected by population sequencing and the sample did not show phenotypic resistance to any approved NNRTIs. 2017 HIV clinical trials Result HIV K101E 73 78 NNRTI;NNRTI 54;243 59;249 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Primary PI resistance substitutions were observed in 1.7% of participants, most commonly M46I/L and L33F in protease. 2017 HIV clinical trials Result HIV L33F;M46I;M46L 100;89;89 104;95;95 PR;PI 108;8 116;10 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Secondary IN resistance substitutions such as S119P and M50I were observed in greater than 50% of participants, and these participants had HIV-1 RNA <50 copies/mL at Week 48 at proportions similar to the overall population, and no development of IN resistance. 2017 HIV clinical trials Result HIV M50I;S119P 56;46 60;51 IN;IN 10;246 12;248 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Specifically, those participants with A62V, V90I, K103N, or E138A/G/K/Q/R in RT, or M46I/L or L33F in PR, had HIV-1 RNA <50 copies/mL at Week 48 after treatment with EVG/COBI/FTC/TDF or ATV+RTV+FTC/TDF at proportions similar to the overall treated population (Table 5). 2017 HIV clinical trials Result HIV A62V;E138A;E138G;E138K;E138Q;E138R;K103N;L33F;M46I;M46L;V90I 38;60;60;60;60;60;50;94;84;84;44 42;73;73;73;73;73;55;98;90;90;48 PR;RT 102;77 104;79 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Ten participants treated with EVG/COBI/FTC/TDF had the polymorphic primary IN resistance substitution T97A by deep sequencing, at percentages ranging from 6.1% to 99.8%, and all of these participants had <50 copies/mL HIV-1 RNA at Week 48 (Table 5). 2017 HIV clinical trials Result HIV T97A 102 106 IN 75 77 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The EVG/COBI/FTC/TDF participant who developed D67D/N did not have post-baseline deep sequencing data available, so this substitution development could not be confirmed. 2017 HIV clinical trials Result HIV D67D;D67N 47;47 53;53 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The most common NNRTI-associated substitutions were V90I, E138A, and K103N. 2017 HIV clinical trials Result HIV E138A;K103N;V90I 58;69;52 63;74;56 NNRTI 16 21 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The most common pre-existing NRTI- and NNRTI-associated substitutions were A62V, V90I, and E138A. 2017 HIV clinical trials Result HIV A62V;E138A;V90I 75;91;81 79;96;85 NNRTI;NRTI 39;29 44;33 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The most common pre-existing NRTI-associated substitution was A62V, observed in 13.6% of participants, all located in Russia (Table 1; Supp. 2017 HIV clinical trials Result HIV A62V 62 66 NRTI 29 33 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The most prevalent secondary IN resistance substitutions observed were S119P and M50I, which are known polymorphisms. 2017 HIV clinical trials Result HIV M50I;S119P 81;71 85;76 IN 29 31 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The three ATV+RTV+FTC/TDF participants who developed M184V/I by population sequencing also had this resistance substitution in their failure sample deep sequencing results (Table 6). 2017 HIV clinical trials Result HIV M184I;M184V 53;53 60;60 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The V90I substitution was seen primarily in participants from Russia (31 of 41 participants with V90I, 75.6%). 2017 HIV clinical trials Result HIV V90I;V90I 4;97 8;101 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. 3A, the K260E and Q264A of GAPDH mutants retained their ability to interact with WT MA. 2016 Biochemistry and biophysics reports Result HIV K260E;Q264A 8;18 13;23 Matrix 84 86 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. 3C, the R58E, Q59A and Q63A of MA mutants did not interact with GAPDH-c. 2016 Biochemistry and biophysics reports Result HIV Q59A;Q63A;R58E 14;23;8 18;27;12 Matrix 31 33 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. 3G, the E79R of CA-NTD mutant retained its ability to interact, but the E76R and R82E mutants lost their ability to interact with GAPDH-c. 2016 Biochemistry and biophysics reports Result HIV E76R;E79R;R82E 72;8;81 76;12;85 Capsid 16 18 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Because MA and CA exist as the precursor protein Pr55gag in HIV-1 producer cells, we next prepared the D256R/K260E/K263E/E267R mutant (M6) of GAPDH. 2016 Biochemistry and biophysics reports Result HIV D256R;E267R;K260E;K263E 103;121;109;115 108;126;114;120 Matrix;Capsid;PR 8;15;49 10;17;51 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Furthermore, Y2H analysis using processing forms of Pr55gag indicated that MA and CA-NTD interact with GAPDH-c. 2016 Biochemistry and biophysics reports Result HIV Y2H 13 16 Matrix;Capsid;PR 75;82;52 77;84;54 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. In addition, combined mutations except for D256R/K260E (M1) caused the loss of interaction. 2016 Biochemistry and biophysics reports Result HIV D256R;K260E 43;49 48;54 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. In contrast, the D256R, K263E or E267R of GAPDH mutants showed the loss of the ability to bind to WT MA. 2016 Biochemistry and biophysics reports Result HIV D256R;E267R;K263E 17;33;24 22;38;29 Matrix 101 103 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. In contrast, the multiple-point mutations of GAPDH, D256R/K260E (M1), D256R/K260E/Q264A (M3) and D256R/K260E/Q264A/E267R (M5) lacked the binding ability to the WT CA-NTD. 2016 Biochemistry and biophysics reports Result HIV D256R;D256R;E267R;K260E;K260E;Q264A;Q264A;D256R;K260E 70;97;115;76;103;82;109;52;58 75;102;120;81;108;87;114;57;63 Capsid 163 165 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. In Y2H analysis using GAPDH mutants and WT MA, as shown in the. 2016 Biochemistry and biophysics reports Result HIV Y2H 3 6 Matrix 43 45 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Since the docking simulation proposed that GAPDH helix 10 is also required for the interaction with CA-NTD, Y2H analysis focusing on the interaction GAPDH and CA-NTD was carried out. 2016 Biochemistry and biophysics reports Result HIV Y2H 108 111 Capsid;Capsid 100;159 102;161 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. The D256R, K260E, K263E, Q264A and E267R of GAPDH single-point mutants maintained the interaction between GAPDH and CA-NTD. 2016 Biochemistry and biophysics reports Result HIV D256R;E267R;K260E;K263E;Q264A 4;35;11;18;25 9;40;16;23;30 Capsid 116 118 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. The Y2H analysis demonstrated that GAPDH helix 10 contributes to the interaction of GAPDH with both MA and CA-NTD. 2016 Biochemistry and biophysics reports Result HIV Y2H 4 7 Matrix;Capsid 100;107 102;109 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Therefore, we prepared the E76R, E79R and R82E of CA-NTD mutants and coexpressed them with GAPDH-c. 2016 Biochemistry and biophysics reports Result HIV E76R;E79R;R82E 27;33;42 31;37;46 Capsid 50 52 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. To further investigate which domain is required for the interactions, we prepared viral proteins- or GAPDH-expression vectors, and performed Y2H analysis. 2016 Biochemistry and biophysics reports Result HIV Y2H 141 144 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Additional passages showed that the proportion of the K43R mutant continuously decreased after each passage and was almost completely replaced by the T/F virus by passage 3. 2017 Retrovirology Result HIV K43R 54 58 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. By day 670, mutations E161Q/S165N and A980V in VF9156-164 and RY10978-986 epitopes were fixed in the viral population, suggesting that these mutations were selected by the T cell responses. 2017 Retrovirology Result HIV A980V;E161Q;S165N 38;22;28 43;27;33 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Mutations (K43R, E161Q/S165N, N242T and N323tc) were at four sites in the gag gene and one mutation (A980V) was at the end of the pol gene. 2017 Retrovirology Result HIV A980V;E161Q;K43R;N242T;S165N 101;17;11;30;23 106;22;15;35;28 Pol;Gag 130;74 133;77 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Our model analysis showed that the K43R mutant was 12% less fit than the cognate T/F virus (- 12% +- 1%; p = 0.003 by t test). 2017 Retrovirology Result HIV K43R 35 39 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The K43R and N323tc mutations are not selected by T cell responses. 2017 Retrovirology Result HIV K43R 4 8 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The K43R mutation causes significant fitness loss. 2017 Retrovirology Result HIV K43R 4 8 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The K43R mutation, located in an HLA-B*35-restricted WF936-44 epitope (WASRELERF) in Gag, was the first detected mutation (day 91). 2017 Retrovirology Result HIV K43R 4 8 Gag 85 88 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The N242T mutation alone had no detectable impact on fitness of the cognate T/F virus. 2017 Retrovirology Result HIV N242T 4 9 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The N242T mutation in the TW10240-249 epitope is a reversion mutation since the subject CH0131 did not have the HLA B*57 allele and was infected with the escape mutant virus. 2017 Retrovirology Result HIV N242T 4 9 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. These results demonstrated that the K43R mutation caused a significantly fitness loss while the N323tc mutation had little impact on viral fitness. 2017 Retrovirology Result HIV K43R 36 40 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. These results demonstrated that the K43R mutation was not selected by classic or cryptic T cell responses. 2017 Retrovirology Result HIV K43R 36 40 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. To determine if the K43R and N323tc mutations affected viral fitness, we introduced each mutation into their cognate T/F infectious molecular clone (IMC) and determined their fitness costs. 2017 Retrovirology Result HIV K43R 20 24 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. To determine if these potentially coded proteins were targeted by T cell responses, we tested all possible peptides containing the K43R mutation for their ability to stimulate T cell responses. 2017 Retrovirology Result HIV K43R 131 135 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. When the K43R mutant was cultured together with the T/F virus, the proportion of the K43R mutant gradually decreased while the T/F virus gradually increased in the culture. 2017 Retrovirology Result HIV K43R;K43R 9;85 13;89 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. For PIs, G73SC and I47VA were observed as the most common minor and major mutations, respectively. 2017 Iranian journal of public health Result HIV G73C;G73S;I47A;I47V 9;9;19;19 14;14;24;24 PI 4 7 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. The most common mutation seen for the NRTIs was M184V and for the NNRTIs was K103N. 2017 Iranian journal of public health Result HIV K103N;M184V 77;48 82;53 NNRTI;NRTI 66;38 72;43 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Among the two TAMs pathways, TAM-2 which features D67N, K70R, T215F, and K219E/Q mutations was more common than the TAM-1 which features M41L, L210W and T215Y. 2017 PloS one Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 50;73;73;56;143;137;62;153 54;80;80;60;148;141;67;158 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Among the virological failed patients only one patient had K103N mutation which confers resistance to NNRTIs. 2017 PloS one Result HIV K103N 59 64 NNRTI 102 108 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. At all-time points, relatively low frequency of K65R mutation was found (Fig 3). 2017 PloS one Result HIV K65R 48 52 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. At T1, the NNRTIs resistance associated mutations were detected at a lower frequency [K103N (n = 2), V106M, Y181S, Y188L, V90I, K101E and G190A (n = 1 each)]. 2017 PloS one Result HIV G190A;K101E;K103N;V106M;V90I;Y181S;Y188L 138;128;86;101;122;108;115 143;133;91;106;126;113;120 NNRTI 11 17 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. But eventually observed in 5/8, 8/11 and 12/15 patients at time point T1 (S2 Table), T2 (Table 1) and T3 (Table 2), respectively with frequent combination of M184V and NNRTI resistance associated mutations. 2017 PloS one Result HIV M184V 158 163 NNRTI 168 173 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. However, in the majority of the patients at all time points, several secondary mutations that may facilitate the development of PI resistance were found at higher frequency which could be naturally occurring minor mutations/polymorphic changes (positions M36I, R41K, H69K, L89M, and I93L) but their clinical significance is uncertain. 2017 PloS one Result HIV H69K;I93L;L89M;M36I;R41K 267;283;273;255;261 271;287;277;259;265 PI 128 130 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Mutations conferring multi-drug resistance such as Q151M and T69ins were not detected. 2017 PloS one Result HIV Q151M;T69ins 51;61 56;67 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. The most frequent NRTIs drug resistance associated mutation is mainly lamivudine-induced mutation M184V which was detected in 4 patients at T1 and showed a 2 fold increase in the following time points (T2: n = 8) and at (T3: n = 12). 2017 PloS one Result HIV M184V 98 103 NRTI 18 23 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. 6), we can reasonably assume a common mechanism of resistance for S217K/H mutants with a steric hindrance effect which is even more accentuated in the case of the S K substitution, explaining the dramatic DTG-binding defect of the S217K mutant. 2017 Scientific reports Result HIV S217H;S217K;S217K 66;66;231 73;73;236 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Based on the strongly reduced activity of G187R compared to the wt IN or S217K, we cannot totally exclude a problem of Mg2+ chelation for G187R that could be indirectly responsible for the DTG-binding defect. 2017 Scientific reports Result HIV G187R;G187R;S217K 42;138;73 47;143;78 IN 67 69 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Consistent with this hypothesis, normalized DTG-binding curves were similar for the wt IN and F190Y indicating that the F Y mutation did not directly and strongly influence DTG binding, in contrast to that observed with G187R or S217K. 2017 Scientific reports Result HIV F190Y;G187R;S217K 94;220;229 99;225;234 IN 87 89 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. DTG binding to analogous G187R and F190Y INPFV was then investigated using fluorescence-based DTG-binding assays and compared to results obtained with the S217K INPFV mutant (equivalent to the RAL/DTG resistant G140S/Q148K INHIV double mutant. 2017 Scientific reports Result HIV F190Y;G140S;G187R;Q148K;S217K 35;211;25;217;155 40;216;30;222;160 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. However, authors exclude that this could be a direct explanation for the decreased INSTI susceptibility of S217H because S217Q and wt INPFV displays similar INST susceptibilities; they show that S217H requires a larger backbone conformational change in the active site, representing a higher energy cost to accommodate the 2nd-generation inhibitor MK2048 compared with S217Q. 2017 Scientific reports Result HIV S217H;S217H;S217Q;S217Q 107;195;121;369 112;200;126;374 INSTI 83 88 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. However, G187R cannot be considered as a catalytic mutant since it sustains a significant ST activity although weak ( 10% of the wt activity. 2017 Scientific reports Result HIV G187R 9 14 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. In the case of S217K, the ST activity was significantly higher ( 60% of the wt activity. 2017 Scientific reports Result HIV S217K 15 20 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Interestingly, X-ray structures of S217Q/H mutants show a loss of metal binding suggesting that the presence of a bulky side chain could be responsible for a reduction in cofactor binding affinity due a displacement of the D185 residue. 2017 Scientific reports Result HIV S217H;S217Q 35;35 42;42 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. No binding of DTG to G187R or S217K was observed whereas a slight but significant decrease of the plateau value was observed with F190Y. 2017 Scientific reports Result HIV F190Y;G187R;S217K 130;21;30 135;26;35 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Recently, we have characterized two new single mutations involving G118 and F121 residues in INHIV that confer resistance against RAL and DTG, albeit to different extents (G118R being more resistant than F121Y). 2017 Scientific reports Result HIV F121Y;G118R 204;172 209;178 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. S217K and G187R displayed highly resistant profiles (IC50 = 500 nM and >1 muM, respectively) while the wt INPFV and the F190Y mutant were similarly inhibited with IC50 values in the 5-15 nM range. 2017 Scientific reports Result HIV F190Y;G187R;S217K 120;10;0 125;15;5 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Taking into account that (i) DTG and MK2048 share similar binding modes in the IN active site and (ii) the decrease in DTG susceptibility is significantly higher for S217K than S217H ( 50-fold and 2-3-fold, respectively). 2017 Scientific reports Result HIV S217H;S217K 177;166 182;171 IN 79 81 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Taking into account that Mg2+ concentration is suboptimal in the fluorescence intensity-based assay (1 mM), the measurement of DTG-binding was repeated in the presence of 10 mM Mg2+ by monitoring DTG anisotropy as described above: the DTG-binding defects of G187R and S217K were consistently observed in this condition. 2017 Scientific reports Result HIV G187R;S217K 258;268 263;273 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. The DTG-binding defects of G187R and S217K mutants are apparently comparable to those observed for the three catalytic triad mutants (D128N, D185N and E221A corresponding to HIV-1 D64N, D116N and E152A, respectively). 2017 Scientific reports Result HIV D116N;D128N;D185N;E152A;E221A;G187R;S217K 186;134;141;196;151;27;37 191;139;146;201;156;32;42 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. To note, the DTG-binding impairment, as observed for the G187R or S217K mutant, was not related to a net decrease of the total amount of IN-DNA complexes. 2017 Scientific reports Result HIV G187R;S217K 57;66 62;71 IN 137 139 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. A direct robust interaction was observed between treatment experience (eRT) and known NRTI-elicited mutations M184I/V and K70E/R. 2017 Viruses Result HIV K70E;K70R;M184I;M184V 122;122;110;110 128;128;117;117 NRTI 86 90 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. A strong interaction also existed between treatment experience and mutation E529D in the RNase H domain, independently of other mutations. 2017 Viruses Result HIV E529D 76 81 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. A total of 9 mutations in RNase H were found positively selected in ART-experienced patients compared to ART-naive patients, these included respectively A435L (5.4% vs. 2017 Viruses Result HIV A435L 153 158 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. A total of 9 mutations in RNase H were found positively selected in ART-experienced patients compared to ART-naive patients, these included respectively A435L (5.4% vs. 1.0%), S468A (5.4% vs. 0.5%), T470S (39.3% vs. 26.1%), L484I (11.6% vs. 3.1%), A508S (6.3% vs. 1.0%), Q509L (4.5% vs. 0.7%), L517I (14.3% vs. 4.6%), Q524E (29% vs. 15.5%) and E529D (20.5% vs. 2.3%) 2017 Viruses Result HIV T470S;L517I;Q509L;S468A;E529D;L484I;A508S;Q524E 199;294;271;176;344;224;248;318 204;299;276;181;349;229;253;323 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. In contrast, mutations E432D, A446S and P537Q occurred at a lower frequency in the treatment-experienced versus naive sequences. 2017 Viruses Result HIV A446S;E432D;P537Q 30;23;40 35;28;45 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Interactions between treatment experience and RNase H domain mutations S468A, A508S and L517I were less robust. 2017 Viruses Result HIV A508S;L517I;S468A 78;88;71 83;93;76 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Only E529D remained significant after adjusting for multiple comparisons (p < 0.001). 2017 Viruses Result HIV E529D 5 10 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Other subtype B resistance-associated mutations found in the naive subtype C sequences were: T470N (13.6%), Q509L (1.6%), K527N (27.1%) and K558R (3.8%). 2017 Viruses Result HIV K527N;K558R;Q509L;T470N 122;140;108;93 127;145;113;98 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Polymorphisms T470S and Q524E, that increased in prevalence following treatment, did not directly interact with any known NRTI-elicited mutations and/or treatment experience, indicating a potential supporting role. 2017 Viruses Result HIV Q524E;T470S 24;14 29;19 NRTI 122 126 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. RNase H mutation S468A was further strongly connected to other RNase H mutations L484I and A435L. 2017 Viruses Result HIV A435L;L484I;S468A 91;81;17 96;86;22 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. The most frequently observed reverse transcriptase (RT) drug resistance mutations in NRTI-experienced patients were M184I/V (64.2%), D67N (25.9%), K70R (19.6%), K219Q/E (17.9%) and T215Y/F (13.4%). 2017 Viruses Result HIV D67N;K219E;K219Q;K70R;M184I;M184V;T215F;T215Y 133;161;161;147;116;116;181;181 137;168;168;151;123;123;188;188 RT;NRTI;RT 29;85;52 50;89;54 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. 1) leading to increased hydrophobic interactions between L33F and the hydrophobic pocket. 2015 Biochemistry and biophysics reports Result HIV L33F 57 61 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. 1B and C), the L33F mutation produces further alterations in many of these residues. 2015 Biochemistry and biophysics reports Result HIV L33F 15 19 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Additionally, in the L33F-DRV complex, the side chains of P2, P1, and P1' of DRV are rotated to compensate for the open S1/S1' subsite. 2015 Biochemistry and biophysics reports Result HIV L33F 21 25 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. As a result, the P2 bis-THF moiety, hydroxyl, and P2' amine of DRV form only three hydrogen bonds with residues D25N, D30, and D29'. 2015 Biochemistry and biophysics reports Result HIV D25N 112 116 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Differences in protein flexibility due to molecular anchoring of L33F should be more pronounced in apo PR compared to PI-complexed forms. 2015 Biochemistry and biophysics reports Result HIV L33F 65 69 PI;PR 118;103 120;105 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. However, the L33F-DRV complex contains an expanded active site and S1/S1' subsite which alters the conformation of P2, P1, P1', and P2' of DRV. 2015 Biochemistry and biophysics reports Result HIV L33F 13 17 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. However, with the L33F mutation, minimal changes in conformation or position occur in either L33F or residues of the hydrophobic pocket upon drug binding in the MDR769 L33F structure. 2015 Biochemistry and biophysics reports Result HIV L33F;L33F 93;18 97;22 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. In addition to the decreased flexibility of the 30s and 80s loops in the MDR769 L33F structures, the L33F mutation restores the noncovalent interactions with the hydrophobic pocket that were originally lost in the MDR769 complex. 2015 Biochemistry and biophysics reports Result HIV L33F 101 105 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. In the L33F-DRV complex, P81 shifts 0.4 A into the active site, but I50' also shifts and rotates leaving a 5.9 A gap which resembles the WT apo structure. 2015 Biochemistry and biophysics reports Result HIV L33F 7 11 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. L33F as a molecular anchor. 2015 Biochemistry and biophysics reports Result HIV L33F 0 4 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Other significant changes due to the L33F mutation are noted in residues I15, K20, A22, V36, L38, I66, and N83. 2015 Biochemistry and biophysics reports Result HIV L33F 37 41 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The decreased flexibility of both the 30s and 80s loops is likely due to enhanced anchoring by L33F via increased hydrophobic interactions within the hydrophobic pocket. 2015 Biochemistry and biophysics reports Result HIV L33F 95 99 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The most notable change is in residue I13, which rotates to avoid steric clashes with L33F. 2015 Biochemistry and biophysics reports Result HIV L33F 86 90 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The side chain of L33F extends 2.2 A deeper into the hydrophobic pocket compared to wild-type (WT) L33. 2015 Biochemistry and biophysics reports Result HIV L33F 18 22 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. These changes lead to increased hydrophobic interactions in L33F compared to the WT and MDR769 structures (Table 1). 2015 Biochemistry and biophysics reports Result HIV L33F 60 64 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Thus, effects of the L33F mutation on the 80s loop and flap tips are possibly implicated in resistance development. 2015 Biochemistry and biophysics reports Result HIV L33F 21 25 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. To further assess the hypothesis of L33F acting as a molecular anchor, 40 ns MD simulations were performed. 2015 Biochemistry and biophysics reports Result HIV L33F 36 40 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. When the 30s loop (residues 29-35) of PR bears the L33F mutation, flexibility of both the 30s and 80s loops (residues 79-84) is decreased, likely through increased hydrophobic interactions. 2015 Biochemistry and biophysics reports Result HIV L33F 51 55 PR 38 40 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Minor mutations found were mainly polymorphisms: K20I/M (21), L10I/V (15), L90W (1), L76S (1), N88D (1), V11I (1), V32L (1) and G48R (1). 2017 BMC research notes Result HIV G48R;K20I;K20M;L10I;L10V;L76S;L90W;N88D;V11I;V32L 128;49;49;62;62;85;75;95;105;115 132;55;55;68;68;89;79;99;109;119 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Of note, Y181C/F and K103N were observed concomitantly in three (7%) cases. 2017 BMC research notes Result HIV K103N;Y181C;Y181F 21;9;9 26;16;16 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Only one patient (< 1%) was reported with major DRMs to protease inhibitors (PI/r), among which M46I, I54V, and V82S, indicating either an event of transmitted PI-associated DRMs or unknown past-exposure to PIs. 2017 BMC research notes Result HIV I54V;M46I;V82S 102;96;112 106;100;116 PR;PI;PI;PI 56;77;160;207 64;79;162;210 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Out of the 43 sequences generated, the most prevalent DRMs were: (67% [29/43] M184V/I, 30% [13/43] T215Y/F, 19% [8/43] V75A/F/I/L/M, 9% [4/43] K70P/R/W, 9% [4/43] K219E/N/Q and 5% [2/43] A62V, followed by other DRMs observed at low rates. 2017 BMC research notes Result HIV A62V;K219E;K219N;K219Q;K70P;K70R;K70W;M184I;M184V;T215F;T215Y;V75A;V75F;V75I;V75L;V75M 187;163;163;163;143;143;143;78;78;99;99;119;119;119;119;119 191;172;172;172;151;151;151;85;85;106;106;131;131;131;131;131 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Out of the 43 sequences generated, the most prevalent DRMs were: 30% [13/43] K103N/S/E, 26% [11/43] Y181C/V/F/L, 2% [1/43] L100I, 2% [1/43] F227L and 2% [1/43] P225H, followed by other DRMs observed at lower rates. 2017 BMC research notes Result HIV F227L;K103E;K103N;K103S;L100I;P225H;Y181C;Y181F;Y181L;Y181V 140;77;77;77;123;160;100;100;100;100 145;86;86;86;128;165;111;111;111;111 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Among the HCV subtypes, 14.6% of RASs in GT-1a were M28 V and Q30H/R, 6.0% in GT-1b were L31F/V and Y93H, and 22.6% in GT-3a were A30K and Y93H. 2017 BMC infectious diseases Result HIV A30K;L31F;L31V;M28V;Q30H;Q30R;Y93H;Y93H 130;89;89;52;62;62;100;139 134;95;95;57;68;68;104;143 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. From monoinfected patients, GT-1a sequences had combinations of M28I + Q30H (1/41; 2.4%) and M28 L + Q30R (1/41; 2.4%), GT-1b had R30K + L31F (1/84; 1.2%), and GT-3a had S62 L + Y93H (1/31; 3.2%) and P58S + Y93H (1/31; 3.2%). 2017 BMC infectious diseases Result HIV L31F;M28I;M28L;P58S;Q30H;Q30R;R30K;S62L;Y93H;Y93H 137;64;93;200;71;101;130;170;178;207 141;68;98;204;75;105;134;175;182;211 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Furthermore, in HCV subtype 1b sequences, P58S (2/84), E62H/E/P (3/84 were E62H, 2/84 were E62E, and 1/84 were E62P), and A92V/T (1/84 were A92V and 4/84 were A92T) polymorphisms were also detected. 2017 BMC infectious diseases Result HIV A92T;A92T;A92V;A92V;E62E;E62E;E62H;E62H;E62P;E62P;P58S 122;159;122;140;55;91;55;75;55;111;42 128;163;128;144;63;95;63;79;63;115;46 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Grouping by HCV subtypes, RASs were detected in 3.9% of GT-1a sequences (M28 T and Q30H/R) and 11.1% of GT-1b sequences (Y93H) (Table 1). 2017 BMC infectious diseases Result HIV M28T;Q30H;Q30R;Y93H 73;83;83;121 79;89;89;125 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. GT-1b sequences contained P58S (3/9) and E62D/V (E62D was found in 1/9 and E62V in 1/9). 2017 BMC infectious diseases Result HIV E62D;E62D;E62V;E62V;P58S 41;49;41;75;26 47;54;47;79;30 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. HCV GT-1a-monoinfected patients more frequently had NS5A RASs than those who were coinfected with HIV/HCV GT-1a (14.6% and 3.9%, respectively; Table 2), highlighting the increased prevalence of Q30H in HCV GT-1a-monoinfected patients. 2017 BMC infectious diseases Result HIV Q30H 194 198 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Meanwhile, GT-3a sequences contained S62 T/Q (S62 T was found in 6/15 and S62Q in1/15). 2017 BMC infectious diseases Result HIV S62Q;S62Q;S62T;S62T 37;74;37;46 44;78;44;52 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. None of the NS5A sequences from HCV GT-1a harbored the Y93H variant (Table 1). 2017 BMC infectious diseases Result HIV Y93H 55 59 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Other polymorphisms also observed in GT-1a sequences were H58S/R/P (H58S was found in 1/77, H58R in 7/77, and H58P in 13/77) and E62D (5/77). 2017 BMC infectious diseases Result HIV E62D;H58P;H58P;H58R;H58R;H58S;H58S 129;58;110;58;92;58;68 133;66;114;66;96;66;73 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. The combinations observed were M28 T + Q30L + H58S (1/77; 1.3%), M28I + H58R (2/77; 2.6%), and Q30R + H58P (1/77; 1.3%). 2017 BMC infectious diseases Result HIV H58P;H58R;H58S;M28I;M28T;Q30L;Q30R 102;72;46;65;31;39;95 106;76;50;69;36;43;99 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. After the inclusion of a few subtype A1 sequences from the Greek epidemic sampled during 2002-2003 as references, the molecular clock signal was significant in both clusters: E138A_1 (R = 0.48, p = 0.014) and E138A_3 (R = 0.28, p = 0.037). 2017 Genes Result HIV E138A;E138A 175;209 180;214 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Although for all E138A LTNs the time of origin was estimated to be several years ago, the number of lineages (transmissions) over time increased in the last few years (2011-2015) (Figure 2b-d), except for E138A_4 that remained in an endemic situation (Re ~ 1) during this period (Figure 2e). 2017 Genes Result HIV E138A;E138A 17;205 22;210 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. For clusters E138A_1 and E138A_3, we found no significant signal, probably due to improper rooting. 2017 Genes Result HIV E138A;E138A 13;25 18;30 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. For E138A LTNs, the Re (median estimates) was higher than 1 for longer time periods (1998-2015) (Figure 2b-d), except the most recent one where the Re was higher than 1 between 2006 and 2011 and approximately equal to 1 thereafter (Figure 2e), and the E138A_1 for which the Re (median estimate) was lower than 1 between 2005 and 2010. 2017 Genes Result HIV E138A;E138A 4;252 9;257 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. For E138A_1, E138A_2, and E138A_3, we found a higher proportion of men who have sex with women (11.8%) (Supplementary Materials Table S1). 2017 Genes Result HIV E138A;E138A;E138A 4;13;26 9;18;31 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. For the remaining three E138A LTNs, Re was 1.8, 2.0, and 2.1 (maximum values of median Re) (Tauable 1). 2017 Genes Result HIV E138A 24 29 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. In contrast to E138A, the origin of K103N and E138A_4 sub-epidemics was estimated to be more recent (2007 and 2004, respectively) (Table 1). 2017 Genes Result HIV E138A;E138A;K103N 15;46;36 20;51;41 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Molecular clock analyses revealed that the time of the most recent common ancestor (tMRCA) was in 2007 (95% highest posterior density (HPD): 2004-2009) for the K103N LTN (Table 1, Figure 1) versus 1995 (95% HPD: 1991-1999), 1996 (95% HPD: 1989-2000), 1997 (95% HPD: 1991-2001), and 2004 (95% HPD: 2000-2007) for E138A LTNs (Table 1). 2017 Genes Result HIV E138A;K103N 312;160 317;165 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Notably, for the K103N LTN, Re (median estimate) was higher than 1 over a period of almost six years (between 2008 and the first half of 2013), and it started declining in the second half of 2013 (Figure 2a). 2017 Genes Result HIV K103N 17 22 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Our study included subtype A1 sequences with the dominant NNRTI-resistant mutations (E138A and K103N) found to spread within major LTNs in Greece; a clustering pattern driven by onward transmissions of NNRTI-resistant viruses. 2017 Genes Result HIV E138A;K103N 85;95 91;100 NNRTI;NNRTI 58;202 63;207 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Overall, K103N and E138A_4 LTNs showed similar characteristics, including a recent tMRCA, the highest slopes and Re, as well as a declining trend in the number of transmissions during the last two years of the study period. 2017 Genes Result HIV E138A;K103N 19;9 24;14 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Plotting the root-to-tip genetic distance against sampling time revealed significant molecular clock signals in LTNs E138A_2 (R = 0.39, p = 0.008), E138A_4 (R = 0.43, p = 0.008), and K103N (R = 0.38, p = 0.009). 2017 Genes Result HIV E138A;E138A;K103N 117;148;183 122;153;188 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Resistance to NNRTIs was the most prevalent (16.9%), and specifically E138A (7.7%), E138Q (4.0%), and K103N (2.3%) were the most common mutations. 2017 Genes Result HIV E138A;E138Q;K103N 70;84;102 75;89;107 NNRTI 14 20 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Similarly, the highest Re was found for K103N (maximum value of median Re = 2.8) and the most recent E138A LTN (maximum value of median Re = 2.5) (E138A_4, Table 1). 2017 Genes Result HIV E138A;E138A;K103N 101;147;40 106;152;45 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Specifically, the slope of the number of lineages (transmissions) over time estimated at the exponential phase of the BDM skylines for E138A sequences was lower (slope = 0.9, 3.2, 3.1 and 5.5) than that for K103N (slope = 10.5). 2017 Genes Result HIV E138A;K103N 135;207 140;212 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. The estimated birth-death skyline plots showed significant differences among E138A and K103N LTNs (sub-epidemics) (Table 1, Figure 2a-e). 2017 Genes Result HIV E138A;K103N 77;87 82;92 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. The latter grouping was made since K103N and E138A_4 had similar characteristics in their transmission dynamics and a more recent tMRCA versus the others. 2017 Genes Result HIV E138A;K103N 45;35 50;40 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. The remaining E138A LTNs showed an approximately steadily increasing epidemic phase lasting for longer time periods. 2017 Genes Result HIV E138A 14 19 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. These findings suggest that three out of four E138A sub-epidemics originated around the same time point (starting between 1995 and 1997) several years ago (Table 1). 2017 Genes Result HIV E138A 46 51 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. To investigate potential differences among the LTNs, we compared populations' characteristics (i) among the five LTNs, and (ii) between K103N and E138A_4, and E138A_1, E138A_2, and E138A_3 LTNs (Table 2, Supplementary Materials Table S1). 2017 Genes Result HIV E138A;E138A;E138A;E138A;K103N 146;159;168;181;136 151;164;173;186;141 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. We found that the distribution of risk groups was different in both comparisons (Table 2, Supplementary Materials Table S1); men who have sex with men (MSM) were at higher proportion in K103N and E138A_4 (77.9%) versus 69.1% for the others (Supplementary Materials Table S1; p < 0.05). 2017 Genes Result HIV E138A;K103N 196;186 201;191 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. Two minor INSTI resistance mutations (T124A, E157Q) and five INSTI-selected mutations (L101I, T122I, T125A, M154I, V201I) covaried with non-resistance-associated variants (Table 4). 2017 Virology journal Result HIV E157Q;L101I;M154I;T122I;T124A;T125A;V201I 45;87;108;94;38;101;115 50;92;113;99;43;106;120 INSTI;INSTI 10;61 15;66 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. Variants L101I, T122I, and V201I with increasing frequency as well as M154I with decreasing frequency were associated with INSTI resistance. 2017 Virology journal Result HIV L101I;M154I;T122I;V201I 9;70;16;27 14;75;21;32 INSTI 123 128 29156603 Adding an Artificial Tail-Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile. However, HIV-1 with E49K mutation in the gp41 NHR became resistant to HP23. 2017 Molecules (Basel, Switzerland) Result HIV E49K 20 24 gp41 41 45 29176596 Quenching protein dynamics interferes with HIV capsid maturation. 1f, h, between gold, magenta, and blue monomers) is less compact than in the CA(A92E) assembly. 2017 Nature communications Result HIV A92E 80 84 Capsid 77 79 29176596 Quenching protein dynamics interferes with HIV capsid maturation. As previously noted for the CA(A92E) assemblies, different H9 crossing angles are present along specific helical arrays in the dimer interfaces, although the extent of variability is less pronounced in the CA(A92E)-SP1 assemblies (Calpha RMSD = 0.9 A between dimers) than in the CA(A92E) assemblies (Calpha RMSD = 2.7 A). 2017 Nature communications Result HIV A92E;A92E;A92E 31;209;282 35;213;286 SP1;Capsid;Capsid;Capsid 215;28;206;279 218;30;208;281 29176596 Quenching protein dynamics interferes with HIV capsid maturation. As we have shown previously, the presence of SP1 modulates the structure of the CA domain, and in the tubular assemblies of CA-SP1 from the HXB2 strain and of CA(A92E)-SP1 from the NL4-3 strain, a number of residues exhibit sizeable CSPs (>0.3 ppm), compared to the corresponding CA assemblies. 2017 Nature communications Result HIV A92E 162 166 SP1;SP1;SP1;Capsid;Capsid;Capsid;Capsid 45;127;168;80;124;159;280 48;130;171;82;126;161;282 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Both the CTD tail and the SP1 region, containing the T8I mutation, give rise to strong, well-defined peaks in dipolar-based correlation spectra, revealing that these segments of the protein are rigid on the microsecond timescale. 2017 Nature communications Result HIV T8I 53 56 SP1 26 29 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Even more strikingly, in the CA-SP1(T8I) mutant, significantly larger chemical shift changes (>1-1.5 ppm) are introduced for many residues, indicating dramatic conformational differences due to this maturation-inhibiting mutation. 2017 Nature communications Result HIV T8I 36 39 SP1;Capsid 32;29 35;31 29176596 Quenching protein dynamics interferes with HIV capsid maturation. For tubular assemblies of WT CA-SP1 and mutant CA(A92E)-SP1, the MAS chemical shifts suggest a predominantly random coil conformation while for tubular CA-SP1(T8I) assemblies, the MAS shifts are indicative of a significant helical propensity for residues 226-231 (CTD) and 1-6 (SP1), see Table 1 and Supplementary Table 1. 2017 Nature communications Result HIV A92E;T8I 50;159 54;162 SP1;SP1;SP1;SP1;Matrix;Matrix;Capsid;Capsid;Capsid 32;56;155;278;65;180;29;47;152 35;59;158;281;67;182;31;49;154 29176596 Quenching protein dynamics interferes with HIV capsid maturation. From a suite of 2D and 3D homo- and heteronuclear correlation spectra, complete site-specific resonance assignments for the CA-SP1(T8I) tubes were obtained, including the CTD tail and the SP1 subdomain. 2017 Nature communications Result HIV T8I 131 134 SP1;SP1;Capsid 127;188;124 130;191;126 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Helix-coil equilibrium of SP1 is modulated by T8I mutation. 2017 Nature communications Result HIV T8I 46 49 SP1 26 29 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In addition, the linker between the NTD and CTD is conformationally less variable in CA(A92E)-SP1 than in CA(A92E) (Calpha RMSD = 0.8 and 2.1 A for CA monomers in a CA(A92E)-SP1 hexamer and a CA(A92E) hexamer, respectively). 2017 Nature communications Result HIV A92E;A92E;A92E;A92E 88;109;168;195 92;113;172;199 SP1;SP1;Capsid;Capsid;Capsid;Capsid;Capsid 94;174;85;106;148;165;192 97;177;87;108;150;167;194 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In both CA(A92E) and CA(A92E)-SP1 tubular assemblies, the atomic models of the CA-NTDs superimpose well (Calpha RMSD = 1.2 A), and the CA-CTD dimer interfaces are also similar in both structures (Calpha RMSD = 1.6 A). 2017 Nature communications Result HIV A92E;A92E 11;24 15;28 SP1;Capsid;Capsid;Capsid;Capsid 30;8;21;79;135 33;10;23;81;137 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In contrast, in CA-SP1 HXB2 and CA(A92E)-SP1 NL4-3 the majority of the residues are in a random coil conformation. 2017 Nature communications Result HIV A92E 35 39 SP1;SP1;Capsid;Capsid 19;41;16;32 22;44;18;34 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In contrast, in our previous work on CA-SP1 HXB2 and CA(A92E)-SP1 NL4-3, resonances of residues in the CTD tail and SP1 were absent in dipolar-based experiments, indicating that in these WT and WT-like proteins the equivalent regions exhibit substantial motions on a timescale of tens of microseconds. 2017 Nature communications Result HIV A92E 56 60 SP1;SP1;SP1;Capsid;Capsid 40;62;116;37;53 43;65;119;39;55 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In contrast, the trimer interface in the CA(A92E)-SP1 assembly. 2017 Nature communications Result HIV A92E 44 48 SP1;Capsid 50;41 53;43 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In this regard, it is interesting to note that chemical shifts calculated using the X-ray diffraction data from the CTD-SP1 crystals (PDB: 5I4T) agree well with the MAS chemical shifts for the CA-SP1(T8I) mutant assembly, but less well with those for WT CA-SP1 assemblies. 2017 Nature communications Result HIV T8I 200 203 SP1;SP1;SP1;Matrix;Capsid;Capsid 120;196;257;165;193;254 123;199;260;167;195;256 29176596 Quenching protein dynamics interferes with HIV capsid maturation. MD simulations of the CA-SP1(T8I) mutant suggested reduced dynamics and increased helical propensity. 2017 Nature communications Result HIV T8I 29 32 SP1;Capsid 25;22 28;24 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Our prior and current MAS NMR results indicate that the SP1 subdomain is dynamic and in a predominantly random coil conformation in CA-SP1 HXB2 and CA(A92E)-SP1 NL4-3 assemblies, while it adopts a stabilized helix in assemblies of CA-SP1(T8I) from the NL4-3 strain. 2017 Nature communications Result HIV A92E;T8I 151;238 155;241 SP1;SP1;SP1;SP1;Matrix;Capsid;Capsid;Capsid 56;135;157;234;22;132;148;231 59;138;160;237;24;134;150;233 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Purified CA(A92E)-SP1 protein assembles well into helical tubes under conditions identical to those used previously for CA(A92E). 2017 Nature communications Result HIV A92E;A92E 12;123 16;127 SP1;Capsid;Capsid 18;9;120 21;11;122 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Remarkably, the T8I mutation in the SP1 subdomain also influences the conformational and dynamic properties in other regions of the CA domain. 2017 Nature communications Result HIV T8I 16 19 SP1;Capsid 36;132 39;134 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The CA(A92E) mutant was used since less bundling of tubes is present, resulting in higher resolution cryo-EM data than for the wild-type (WT) CA[4], in addition to attenuating the CypA-binding loop dynamics[32]. 2017 Nature communications Result HIV A92E 7 11 Capsid;Capsid 4;142 6;144 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The cryo-EM structure of the CA(A92E)-SP1 tubular assembly was determined from 33 tubes at 8 A resolution. 2017 Nature communications Result HIV A92E 32 36 SP1;Capsid 38;29 41;31 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The experimental chemical shifts indicate that the T8I mutation in SP1 results in increased helical content (Table 1), with residues H226(CA)-Q6(SP1) forming a contiguous helix. 2017 Nature communications Result HIV T8I 51 54 SP1;SP1;Capsid 67;145;138 70;148;140 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The overall reduction in dynamics throughout the T8I mutant protein is also supported by the smaller number of resonances in scalar-based correlation MAS NMR spectra of tubular CA-SP1(T8I) assemblies, compared to those of CA(A92E)-SP1. 2017 Nature communications Result HIV A92E;T8I;T8I 225;49;184 229;52;187 SP1;SP1;Matrix;Capsid;Capsid 180;231;150;177;222 183;234;152;179;224 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The T8I mutation induces a helical conformation in SP1. 2017 Nature communications Result HIV T8I 4 7 SP1 51 54 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The T8I mutation induces allosteric changes in the CA domain. 2017 Nature communications Result HIV T8I 4 7 Capsid 51 53 29176596 Quenching protein dynamics interferes with HIV capsid maturation. These conformational differences are linked to a change in the overall dynamics of the CA domain, and the microsecond-millisecond motions are reduced, as evidenced by increased peak intensities throughout the CA-SP1(T8I) spectrum. 2017 Nature communications Result HIV T8I 216 219 SP1;Capsid;Capsid 212;87;209 215;89;211 29176596 Quenching protein dynamics interferes with HIV capsid maturation. This corroborates our MAS NMR-based observation that the predominant major structure is helical in the T8I mutant and suggests that longer MD simulations may be needed to possibly observe the six-helix bundle. 2017 Nature communications Result HIV T8I 103 106 Matrix 22 24 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Thus, overall the T8I change reduced the dynamics of CA, rendering it conformationally less flexible. 2017 Nature communications Result HIV T8I 18 21 Capsid 53 55 29176596 Quenching protein dynamics interferes with HIV capsid maturation. To further assess the structure and motions in the SP1 region, we performed simulated tempering MD calculations over 15-24 micros of a hexameric subunit of CTD-SP1 HXB2 as well as the CTD-SP1(T8I) HXB2. 2017 Nature communications Result HIV T8I 192 195 SP1;SP1;SP1 51;160;188 54;163;191 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Assessed by BN-PAGE gel electrophoresis and Western blotting, each of the single mutants formed trimers efficiently, but the two double mutants S306L/A316W and S306L/R308L and the S306L/R308L/A316W triple mutant were somewhat less efficiently expressed compared with the unmodified SOSIP.664 trimer. 2018 The Journal of biological chemistry Result HIV A316W;R308L;S306L;A316W;R308L;S306L;S306L 192;186;180;150;166;144;160 197;191;185;155;171;149;165 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Compared with SOSIP.664 and SOSIP.v5.2, a highly significant reduction in MW965.26 neutralization was seen for SOSIP.v5.2 S306L/R308L immunized rabbits of 154- and 12-fold respectively (p = 0.01 for SOSIP.v5.2 S306L/R308L versus SOSIP.v5.2 and p = 0.001 for SOSIP.v5.2 S306L/R308L versus SOSIP.664, respectively). 2018 The Journal of biological chemistry Result HIV R308L;R308L;R308L;S306L;S306L;S306L 128;216;275;122;210;269 133;221;280;127;215;274 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Converse to the reduction in V3 antigenicity, the S306L plus R308L paired substitutions had no effect on the trimer reactivity of bNAbs targeting other epitopes (2G12, VRC01, PGT145, PGT151, and PGT126), including those that recognize quaternary epitopes that are highly sensitive to the overall conformation of the trimer. 2018 The Journal of biological chemistry Result HIV R308L;S306L 61;50 66;55 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. However, when introduced together (S306L/R308L), and more so in combination with the A316W change (S306L/R308L/A316W), they greatly reduced or completely abrogated the binding of all three V3 non-NAbs without affecting the reactivity of the 2G12 bNAb with its oligomannose patch epitope and the quaternary dependent bNAb PGT151. 2018 The Journal of biological chemistry Result HIV A316W;R308L;S306L;A316W;R308L;S306L 111;105;99;85;41;35 116;110;104;90;46;40 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. In contrast, four of the five sera from the SOSIP.v5.2 S306L/R308L-immunized rabbits lacked any ability to neutralize the SF162 virus, and only a minimal response was found for the fifth serum (ID50 of 27. 2018 The Journal of biological chemistry Result HIV R308L;S306L 61;55 66;60 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Next, we measured neutralization of the autologous tier 2 virus BG505.T332N virus. 2018 The Journal of biological chemistry Result HIV T332N 70 75 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. None of the sera consistently neutralized any of the heterologous tier 2 viruses tested, except for animal 1834, which received BG505 SOSIP.v5.2 S306L/R308L (Tables 3 and 4). 2018 The Journal of biological chemistry Result HIV R308L;S306L 151;145 156;150 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Overall, there was a 10-fold reduction in median SF162 ID50 for the SOSIP.v5.2 S306L/R308L group compared with SOSIP.664 (p = 0.001) and a 5-fold reduction compared with SOSIP.v5.2 (p = 0.02). 2018 The Journal of biological chemistry Result HIV R308L;S306L 85;79 90;84 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Overall, we conclude from the V3-peptide serology studies that the V3 domain on the SOSIP.v5.2 S306L/R308L trimer was a little less immunogenic than on the SOSIP.v5.2 version and that the introduced leucine residues did not create highly immunogenic V3 neo-epitopes. 2018 The Journal of biological chemistry Result HIV R308L;S306L 101;95 106;100 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Sera from the SOSIP.v5.2 S306L/R308L recipients bound comparably to the two V3 peptide variants. 2018 The Journal of biological chemistry Result HIV R308L;S306L 31;25 36;30 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Sera from the SOSIP.v5.2 S306L/R308L-immunized rabbits bound comparably to the sequence-modified and parental trimers, indicating that the induced Abs predominantly recognized epitopes shared between these two trimers. 2018 The Journal of biological chemistry Result HIV R308L;S306L 31;25 36;30 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Specifically, we immunized rabbits with PGT145-purified BG505 SOSIP.v5.2 or SOSIP.v5.2 S306L/R308L trimers at weeks 0, 4 and 20, and compared trimer-binding and virus-neutralizing Ab responses at week 22. 2018 The Journal of biological chemistry Result HIV R308L;S306L 93;87 98;92 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The A316W single mutant was also poorly infectious, consistent with our earlier report. 2018 The Journal of biological chemistry Result HIV A316W 4 9 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The antigenicity of the same five PGT145-purified trimers was studied by ELISA, to further assess whether the S306L and R308L substitutions had decreased the presentation of the V3 epitopes for mAbs 39F, 4F5, 447-52D, and 19b. 2018 The Journal of biological chemistry Result HIV R308L;S306L 120;110 125;115 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The BG505 SOSIP.v4.1 and SOSIP.v5.2 designs of stabilized Env trimer both already include the A316W substitution in V3. 2018 The Journal of biological chemistry Result HIV A316W 94 99 Env 58 61 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The individual S306L and R308L point substitutions did not markedly affect the trimer binding of the V3 non-NAbs. 2018 The Journal of biological chemistry Result HIV R308L;S306L 25;15 30;20 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The individual S306L and R308L substitutions decreased infectivity by 2- and 5-fold, respectively, and when combined, by 10-fold. 2018 The Journal of biological chemistry Result HIV R308L;S306L 25;15 30;20 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The midpoint of thermal denaturation (Tm) of 72.6 C for the SOSIP.v4.1 S306L/R308L trimer was higher than the value of 69.5 C for SOSIP.v4.1, and likewise for SOSIP.v5.2 S306L/R308L compared with SOSIP.v5.2 (78.1 C versus 74.2 C. 2018 The Journal of biological chemistry Result HIV R308L;R308L;S306L;S306L 78;178;72;172 83;183;77;177 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The S306L plus R308L-substituted trimers were predominantly (>95%) native-like when visualized by negative-stain electron microscopy (NS-EM), indicating that these V3 changes do not have global adverse effects on trimer conformation (Table 2 and. 2018 The Journal of biological chemistry Result HIV R308L;S306L 15;4 20;9 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The stabilization effect of the two substitutions described here and the previously described substitutions A316W and E64K, and the 73C-561C disulfide bond are additive. 2018 The Journal of biological chemistry Result HIV A316W;E64K 108;118 113;122 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The yields of the S306L plus R308L-substituted SOSIP.v4.1 and SOSIP.v5.2 trimers, ~1.0 and ~0.5 mg/liter, respectively, were reduced compared with the unmodified SOSIP.v4.1 and SOSIP.v5.2 versions, ~2.0 mg/liter in both cases (Table 2). 2018 The Journal of biological chemistry Result HIV R308L;S306L 29;18 34;23 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. There was a generally strong autologous NAb response in the SOSIP.v5.2 and SOSIP.v5.2 S306L/R308L immunized rabbits, with median titers of 3761 and 1415, respectively. 2018 The Journal of biological chemistry Result HIV R308L;S306L 92;86 97;91 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Thus, the median ID50 against this virus was 4166 for the SOSIP.664 historic control group, 328 for SOSIP.v5.2, but only 27 for SOSIP.v5.2 S306L/R308L. 2018 The Journal of biological chemistry Result HIV R308L;S306L 145;139 150;144 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Thus, the S306L and R308L substitutions increased trimer thermostability by 3-4 C, which is consistent with our earlier finding for the A316W change. 2018 The Journal of biological chemistry Result HIV A316W;R308L;S306L 137;20;10 142;25;15 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Tier 1A viruses that are highly neutralization sensitive are particularly vulnerable to V3 Abs that lack the ability to neutralize tier 2 viruses such as, but not limited to, BG505.T332N. 2018 The Journal of biological chemistry Result HIV T332N 181 186 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. To determine the effect of the S306L and R308L substitutions on Env function, we introduced them into the infectious BG505.T332N Env-pseudotyped virus and measured infectivity on TZM-bl cells. 2018 The Journal of biological chemistry Result HIV R308L;S306L;T332N 41;31;123 46;36;128 Env;Env 64;129 67;132 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. To further decrease V3 immunogenicity, we carried out a structure-guided redesign in the V3 region of the BG505 SOSIP.v4.1 and SOSIP.v5.2 trimers that already contain the A316W substitution. 2018 The Journal of biological chemistry Result HIV A316W 171 176 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. To gain insights into the V3 Ab response, we measured Ab titers to the wildtype BG505 V3 peptide and a variant containing the S306L/R308L/A316W sequence changes present in the SOSIP.v5.2 S306L/R308L trimer. 2018 The Journal of biological chemistry Result HIV A316W;R308L;S306L;R308L;S306L 138;132;126;193;187 143;137;131;198;192 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We do not know whether this unusually strong cross-neutralizing response is attributable to chance or whether the introduction of the S306L and R308L substitutions played a role. 2018 The Journal of biological chemistry Result HIV R308L;S306L 144;134 149;139 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We first determined binding Ab titers to the BG505 SOSIP.v5.2 S306L/R308L and SOSIP.664 trimers. 2018 The Journal of biological chemistry Result HIV R308L;S306L 68;62 73;67 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We first introduced the S306L, R308L, and A316W substitutions into a D7324-tagged version of the BG505 SOSIP.664 trimer, alone and in combination; transiently expressed the proteins in 293T cells; and analyzed the unpurified Env proteins in the culture supernatants. 2018 The Journal of biological chemistry Result HIV A316W;R308L;S306L 42;31;24 47;36;29 Env 225 228 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We next assessed the thermostability of the SOSIP.v4.1 S306L/R308L and SOSIP.v5.2 S306L/R308L proteins and their unmodified comparators by differential scanning calorimetry (DSC). 2018 The Journal of biological chemistry Result HIV R308L;R308L;S306L;S306L 61;88;55;82 66;93;60;87 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We now introduced the paired S306L and R308L substitutions into these constructs, to make the SOSIP.v4.1 S306L/R308L and SOSIP.v5.2 S306L/R308L variants. 2018 The Journal of biological chemistry Result HIV R308L;R308L;R308L;S306L;S306L;S306L 39;111;138;29;105;132 44;116;143;34;110;137 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We observed that the ability of soluble CD4 to induce the exposure of the 17b epitope was strongly impaired for trimers containing the S306L plus R308L substitutions. 2018 The Journal of biological chemistry Result HIV R308L;S306L 146;135 151;140 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We previously found that the introduction of an A316W mutation into V3 reduced the exposure of this Env domain on the trimer surface and thereby reduced the induction of V3-directed non-NAbs by ~10-fold when the resulting SOSIP.v4 trimers were tested as immunogens in mice and rabbits, but to a lesser extent in macaques. 2018 The Journal of biological chemistry Result HIV A316W 48 53 Env 100 103 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. When all substitutions are considered in the BG505 SOSIP.v5.2 S306L/R308L trimer, its stability is increased by 11.4 C (from BG505 SOSIP.664 to BG505 SOSIP.v5.2 S306L/R308L; Table 1 and. 2018 The Journal of biological chemistry Result HIV R308L;R308L;S306L;S306L 68;168;62;162 73;173;67;167 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. When the S306L plus R308L substitutions were present in the SOSIP.v4.1 and SOSIP.v5.2 constructs, there was no detectable binding of 39f, 4F5, and 447-52D, and 19b binding was further reduced compared with the unmodified trimers. 2018 The Journal of biological chemistry Result HIV R308L;S306L 20;9 25;14 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. Amplification is similar for both wild type and M184V HIV DNA, and a lower limit of 100 copies of target DNA is detectable via gel electrophoresis. 2018 Analytical biochemistry Result HIV M184V 48 53 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Among the NNRTI failure patients, two patients had K103N and V106M/Y188CH mutation respectively. 2018 AIDS (London, England) Result HIV K103N;V106M;Y188C;Y188H 51;61;67;67 56;66;73;73 NNRTI 10 15 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Five patients (21%) with multiple mutations (Q148QR+N155H, G140A+Q148R, E138K+G140S+Q148R, E138K+G140A+ S147SG+Q148K and G140S+Q148H+N155H) were predicted to have high-level cross resistance to DTG, CAB, and BIC, although no phenotypic assessment has confirmed this observation. 2018 AIDS (London, England) Result HIV E138K;E138K;G140A;G140A;G140S;G140S;N155H;N155H;Q148H;Q148K;Q148Q;Q148R;Q148R;Q148R;S147G;S147S 72;91;59;97;78;121;52;133;127;111;45;45;65;84;104;104 77;96;64;102;83;126;57;138;132;116;52;52;70;89;110;110 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. In addition, 17 of 270 (6.3%) patients had at least one major accessory DRM: T97A (n=3), E157Q (n=12), or A128T (n=2). 2018 AIDS (London, England) Result HIV A128T;E157Q;T97A 106;89;77 111;94;81 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. None of the INSTI-naive subjects had NRTI mutations; however, three individuals had NNRTIs DRM (V106M, K103N, G190A). 2018 AIDS (London, England) Result HIV G190A;K103N;V106M 110;103;96 115;108;101 INSTI;NNRTI;NRTI 12;84;37 17;90;41 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. One HIV-1B patient had a major primary INSTI-DRM, T66I (Supplementary Digital Content 1). 2018 AIDS (London, England) Result HIV T66I 50 54 INSTI 39 44 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. One of the two patients who switched with suppressive viremia, maintained undetectable viral load, but one (with T97A) had a viral blip at month 6 (57 copies/mL) (Fig 3a). 2018 AIDS (London, England) Result HIV T97A 113 117 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Sequencing of samples collected 1216 and 1038 days earlier from these two patients showed that they had E157Q and the T97A mutations, respectively. 2018 AIDS (London, England) Result HIV E157Q;T97A 104;118 109;122 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. The A128T is a non-polymorphic mutation selected in vitro by EVG, but does not appear to reduce INSTI susceptibility ex vivo. 2018 AIDS (London, England) Result HIV A128T 4 9 INSTI 96 101 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. The naturally occurring polymorphism M50I was found in 49 (18%) of the INSTI-naive patients. 2018 AIDS (London, England) Result HIV M50I 37 41 INSTI 71 76 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Two RAL treated patients with E157Q and T97A mutations, respectively, failed to suppress viremia at month six. 2018 AIDS (London, England) Result HIV E157Q;T97A 30;40 35;44 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. Amongst treatment defaulters (n = 5), 4 had the K103N mutation and 1 had the V106M mutation. 2017 PloS one Result HIV K103N;V106M 48;77 53;82 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. Amongst treatment naive FSWs, 20 had the NNRTI mutations K103N, 4 had the K101E or V106E mutations. 2017 PloS one Result HIV K101E;K103N;V106E 74;57;83 79;62;88 NNRTI 41 46 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. For those on treatment (n = 14), 7 had the K103N mutations and 5 had the V106M or G190A mutations, and 2 and the K101E mutations. 2017 PloS one Result HIV G190A;K101E;K103N;V106M 82;113;43;73 87;118;48;78 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. Overall, the number of FSWs with the K103N mutation was 68.9% (31/45), the K101E mutation was found in 6/45 (13.3%), the V106M mutation in 10/45 (22.2%), G190A in 5/45 (11.1%), and the NRTI mutation M184V was present in 13/45 (28.9%) of SWs. 2017 PloS one Result HIV G190A;K101E;K103N;M184V;V106M 154;75;37;199;121 159;80;42;204;126 NRTI 185 189 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. The NRTI mutation M184V was also found in 1 participant. 2017 PloS one Result HIV M184V 18 23 NRTI 4 8 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. 293T cells were transfected with WT, N65A, N92A, and N65,92A mutant tetherin expression vectors that carry an HA-tag in the extracellular CC domain. 2018 Viruses Result HIV N65A;N92A 37;43 41;47 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. As expected, kifunensine treatment resulted in the expression of 23-kDa and 24.5-kDa tetherin species, but not the complex-type tetherins ( 26 to 32 kDa) for both N65A and N92A single-Asn mutants (Figure 5A). 2018 Viruses Result HIV N65A;N92A 163;172 167;176 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. As reported previously, the single mutants, N65A and N92A, inhibited the release of both delVpu and Udel particles to a similar extent as WT tetherin (Figure 1B). 2018 Viruses Result HIV N65A;N92A 44;53 48;57 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. To determine whether complex-type oligosaccharide modification of tetherin that is glycosylated on a single residue is also dispensable for the inhibition of virus release, 293T cells were transfected with pNL4-3delVpu, and WT and tetherin mutants (N65A, N92A, and N65,92A), treated with kifunensine for 24 h, and virus release was monitored. 2018 Viruses Result HIV N65A;N92A 249;255 253;259 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. We transfected 293T cells, which do not express endogenous tetherin, with WT and Vpu-defective HIV-1 and analyzed virus release in the presence of WT and glycosylation-defective single (N65A or N92A) or double (N65,92A) mutants of human tetherin. 2018 Viruses Result HIV N65A;N92A 186;194 191;198 Vpu 81 84 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. 1a) but a third resistant variant appeared, N155H which already comprised 13% of the population. 2018 Retrovirology Result HIV N155H 44 49 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. 1a) the N155H variant replaced the Q148R variant and dominated the population together with the E138K + Q148K variant. 2018 Retrovirology Result HIV E138K;N155H;Q148K;Q148R 96;8;104;35 101;13;109;40 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. 1c) and the viral population contained N155H mutants. 2018 Retrovirology Result HIV N155H 39 44 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. 1e) by double mutant G140S + Q148H. 2018 Retrovirology Result HIV G140S;Q148H 21;29 26;34 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. 1e) mutations from all three major resistance pathways including double mutants with secondary mutations were observed with G140S + Q148H being the most frequently occurring double mutant. 2018 Retrovirology Result HIV G140S;Q148H 124;132 129;137 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. 2), including T97A and Y143C (both 0.2%). 2018 Retrovirology Result HIV T97A;Y143C 14;23 18;28 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. 40 days after start of raltegravir, virus with Q148R had increased to 1.7% of the population and virus with E138K + Q148K had increased to 0.5%. 2018 Retrovirology Result HIV E138K;Q148K;Q148R 108;116;47 113;121;52 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. A third culture only selected an L68V substitution, but this virus did not demonstrate phenotypic resistance when tested (data not shown). 2018 Retrovirology Result HIV L68V 33 37 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. After 169 days the resistant population had shifted dramatically, with Y143R making up 99.7% of the population and complete absence of N155H. 2018 Retrovirology Result HIV N155H;Y143R 135;71 140;76 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. After brief virological suppression (HIV-1 RNA < 50 c/ml, a 3.0 log decrease in HIV-1 RNA), viral load rebounded and population sequencing showed gradual accumulation of raltegravir resistance mutations: initially primary resistance mutation N155H appeared followed by two secondary resistance mutations, first Q95K and later V151I. 2018 Retrovirology Result HIV N155H;Q95K;V151I 242;311;326 247;315;331 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Before raltegravir therapy, mutation Y143H was detected at low frequency (0.2%) by NGS but did not appear in any of the later samples during raltegravir treatment. 2018 Retrovirology Result HIV Y143H 37 42 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Culture #1 initially selected G140S + Q148R but later switched to Q148H (not shown). 2018 Retrovirology Result HIV G140S;Q148H;Q148R 30;66;38 35;71;43 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Cultures #1 and #2 both developed raltegravir resistance through G140S + Q148H. 2018 Retrovirology Result HIV G140S;Q148H 65;73 70;78 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. G140S was probably not selected because it required two nucleotide changes in this HXB2 background; G140A and E138K required just one. 2018 Retrovirology Result HIV E138K;G140A;G140S 110;100;0 115;105;5 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. HXB2 virus predominantly selected mutation Q148K (in three out of the five independent cultures), N155H was selected once and in one culture only secondary resistance mutations emerged. 2018 Retrovirology Result HIV N155H;Q148K 98;43 103;48 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In a later time-point, 169 days after start of raltegravir, this population was replaced by a variant with primary mutation Y143R and several secondary mutations including L74M, T97A and G163E. 2018 Retrovirology Result HIV G163E;L74M;T97A;Y143R 187;172;178;124 192;176;182;129 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In a sample taken 28 days later, 77.5% of the population contained N155H, 15.4% had T97A and variants with Y143C were not detected anymore. 2018 Retrovirology Result HIV N155H;T97A;Y143C 67;84;107 72;88;112 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In Pt1, resistance developed initially through E138K + Q148K and later a second variant emerged with N155H. 2018 Retrovirology Result HIV E138K;N155H;Q148K 47;101;55 52;106;60 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In Pt2, raltegravir resistance developed initially through N155H and was complemented by two secondary mutations, Q95K and V151I, which made up nearly 100% of the viral population during prolonged therapy failure. 2018 Retrovirology Result HIV N155H;Q95K;V151I 59;114;123 64;118;128 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In the subsequent sample 70 days after start of raltegravir therapy, N155H had increased to 88.6% and Y143C had reappeared in 11.8% of the reads. 2018 Retrovirology Result HIV N155H;Y143C 69;102 74;107 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In this sample the variant with mutation N155H was the dominant variant but was outcompeted in the subsequent sample (red nodes. 2018 Retrovirology Result HIV N155H 41 46 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In vivo, only mutations relating to the N155H pathway were observed and no other significant mutations were detected by deep sequencing. 2018 Retrovirology Result HIV N155H 40 45 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Interestingly, in the two other cultures, N155H emerged in combination with amino acid substitutions at position 143 (one with Y143C and one with Y143R. 2018 Retrovirology Result HIV N155H;Y143C;Y143R 42;127;146 47;132;151 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Mutations L74M, T97A and G163R appeared in nearly the entire viral population. 2018 Retrovirology Result HIV G163R;L74M;T97A 25;10;16 30;14;20 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. N155H was found in 14.4%, of the population, Q148H in 7.5% of which approximately half (4.1%) in combination with G140S and the remainder in combination with E157D. 2018 Retrovirology Result HIV E157D;G140S;Q148H;N155H 158;114;45;0 163;119;50;5 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. NGS revealed very small populations at baseline containing Q148R and E138K (0.1% of the population. 2018 Retrovirology Result HIV E138K;Q148R 69;59 74;64 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Population sequencing (sample 457 days after initiation of raltegravir) demonstrated that virus with integrase substitutions G140S + Q148H completely dominated the viral population. 2018 Retrovirology Result HIV G140S;Q148H 125;133 130;138 IN 101 110 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Population sequencing revealed presence of raltegravir resistance mutations (E138E/K + Q148Q/K/R + N155H/H) and raltegravir was discontinued from the regimen after 124 days. 2018 Retrovirology Result HIV E138E;E138K;N155H;Q148K;Q148Q;Q148R 77;77;99;87;87;87 85;85;106;96;96;96 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Q148R was present in 2.4% of the population and G163R in 2.7%. 2018 Retrovirology Result HIV G163R;Q148R 48;0 53;5 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Sanger sequencing revealed only very small (< 20%) populations of Q148H/Q148R and N155H and resistant variants never dominated the population. 2018 Retrovirology Result HIV N155H;Q148H;Q148R 82;66;72 87;71;77 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. The N155H-virus additionally acquired mutations V151I and later E92Q. 2018 Retrovirology Result HIV E92Q;N155H;V151I 64;4;48 68;9;53 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Two of the Q148K mutations were accompanied by G140A, the third by E138K. 2018 Retrovirology Result HIV E138K;G140A;Q148K 67;47;11 72;52;16 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Y143C and N155H did not appear to be on the same genome. 2018 Retrovirology Result HIV N155H;Y143C 10;0 15;5 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. In addition, the average first viral load was 4.9 Log10 copies/mL (4.3-5.5), with a zenith value of 5.0 Log10 copies/mL (4.5-5.5), this latter being lower in patients with the G190A mutation (4.7 vs. 2018 PloS one Result HIV G190A 176 181 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. In addition, we also detected in 8 patients (14.0%) the polymorphic mutation V179I/A, though this possesses little direct effect on NNRTI susceptibility. 2018 PloS one Result HIV V179A;V179I 77;77 84;84 NNRTI 132 137 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Other demographic and clinical data about our cohort as well as the detailed comparison between the groups with and without the G190A mutation are depicted in Table 2. 2018 PloS one Result HIV G190A 128 133 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Regarding antiretroviral drug resistance, we found the G190A mutation associated with different levels of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance in 29 out of 57 patients with the subtype CRF19_cpx (50.9%), including all the patients from clusters A to D (Fig 3). 2018 PloS one Result HIV G190A 55 60 NNRTI;NNRTI 106;154 142;159 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Unlike G190A mutation clusters, the patients with the V179 polymorphism did not show any clear grouping with each other, as depicted in Fig 3 as well as S3 and S4 Figs in Supplementary material. 2018 PloS one Result HIV G190A 7 12 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Error rates of 3.3 x 10-5 were estimated for the O_K65R/V75I RT under those conditions (Table 4). 2018 Scientific reports Result HIV K65R;V75I 51;56 55;60 RT 61 63 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. In previous studies, we found that the mutant O_K65R/V75I RT was >15-fold more accurate than the HIV-1BH10 RT in forward mutation assays measuring fidelity of DNA-dependent DNA synthesis. 2018 Scientific reports Result HIV K65R;V75I 48;53 52;57 RT;RT 58;107 60;109 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. In the case of HIV-1BH10, HIV-1ESP49 and the O_K65R RTs, the large deletions clustered at positions +172/+173 (Supplementary Figs S2-S4), corresponding to the first two nucleotides incorporated during reverse transcription. 2018 Scientific reports Result HIV K65R 47 51 RT;RT 201;52 222;55 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Interestingly, the analysis of mutational spectra revealed that major hotspots obtained with O_K65R/V75I RT while reverse transcribing an RNA template synthesized at pH 7.9/6 mM Mg2. 2018 Scientific reports Result HIV K65R;V75I 95;100 99;104 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Interestingly, the spectrum of the O_K65R/V75I RT showed an important hotspot at position +147 (U-to-C substitutions). 2018 Scientific reports Result HIV K65R;V75I 37;42 41;46 RT 47 49 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Meanwhile, the smaller reduction in the error rate (1.1-fold) observed with O_K65R/V75I RT when changing transcription conditions might be attributed to the use of commercial T7 RNAP to synthesize the RNA templates. 2018 Scientific reports Result HIV K65R;V75I 78;83 82;87 RT 88 90 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Mutant O_K65R/V75I RT had a low tendency to introduce frameshifts, although it had a relatively high base substitution error rate. 2018 Scientific reports Result HIV K65R;V75I 9;14 13;18 RT 19 21 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Similar experiments with O_K65R/V75I RT and RNAs transcribed at pH 6.75/1.5 mM Mg2+ showed error rates of 3.3 x 10-5 and 2.3 x 10-5 for recombinant and commercial T7 RNAPs, respectively. 2018 Scientific reports Result HIV K65R;V75I 27;32 31;36 RT 37 39 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. The highest error rates were obtained with WT HIV-1BH10 RT, while one of the most faithful enzymes was the double-mutant O_K65R/V75I that showed 1.4-fold increased accuracy relative to the HIV-1BH10 RT. 2018 Scientific reports Result HIV K65R;V75I 123;128 127;132 RT;RT 56;199 58;201 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. The origin of the T7 RNAP had a minor effect on hotspot distribution in the O_K65R/V75I spectra when the template RNA was synthesized at lower pH and magnesium concentration (Supplementary Figs S11 and S12). 2018 Scientific reports Result HIV K65R;V75I 78;83 82;87 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. The smaller differences observed with the O_K65R/V75I RT relative to the HIV-1BH10 RT can be attributed to the existence of a transcriptional threshold that has a bigger influence on more faithful RTs. 2018 Scientific reports Result HIV K65R;V75I 44;49 48;53 RT;RT;RT 54;83;197 56;85;200 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. The spectrum induced by the single-mutant O_K65R had one hotspot at position +109. 2018 Scientific reports Result HIV K65R 44 48 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Unlike in the case of O_K65R/V75I, this strong bias towards the generation of transitions was not observed with the other RTs studied. 2018 Scientific reports Result HIV K65R;V75I 24;29 28;33 RT 122 125 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. We determined mutant frequencies and error rates of RNA-dependent DNA synthesis for WT MLV, AMV, HIV-1BH10 and HIV-1ESP49 RTs, as well as mutant RTs O_K65R and O_K65R/V75I. 2018 Scientific reports Result HIV K65R;K65R;V75I 151;162;167 155;166;171 RT;RT 122;145 125;148 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Also, the H69D fusion precursors without MBP SigP showed partial autoprocessing activities (lanes 33-36). 2018 PloS one Result HIV H69D 10 14 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. As shown in Fig 2B, with C2-MBP fusion H69D autoprocessing was partially inhibited as indicated by detection of autoprocessing products plus the full length precursor (Fig 2B, lane 14), which was similar to the outcome of GST fusion. 2018 PloS one Result HIV H69D 39 43 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Collectively, the L-MBP appeared to influence H69D precursor autoprocessing in a p6*-independent manner. 2018 PloS one Result HIV H69D 46 50 Gag 81 83 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Furthermore, SR2a could recapitulate SHC's effects whereas SR2b displayed a mixed phenotype as it released self-degradation-sensitive mature PR (S3 Fig, lanes 11, 12) but suppressed H69D autoprocessing (S3 Fig, lanes 31, 32). 2018 PloS one Result HIV H69D 182 186 PR 141 143 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Having confirmed that the GFP tag did not alter precursor autoprocessing ability, GFP fusions carrying D25N (to prevent autoprocessing) with or without SigP were examined in transfected HeLa cells by confocal microscopy. 2018 PloS one Result HIV D25N 103 107 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In any case, the H69D mutation in the context of the M6 precursor behaved the same as the D25N mutation (lanes 28, 29). 2018 PloS one Result HIV D25N;H69D 90;17 94;21 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In contrast, with L-MBP fusion H69D completely suppressed precursor autoprocessing as only the full-length precursor was detected and was comparable to the D25N control (Fig 2B, lane 5). 2018 PloS one Result HIV D25N;H69D 156;31 160;35 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In contrast, with SigP or SigL fusion, H69D was mostly autoprocessing-deficient, similar to the D25N controls, showing no difference in detection of the full-length precursor with or without 5 muM DRV (Fig 3C lanes 12, 13, 18, 19). 2018 PloS one Result HIV D25N;H69D 96;39 100;43 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In the context of SB, H69D autoprocessing was partially active (S3 Fig, lane 25), which was like the Flag-M1 H69D control (Fig 3C, lane 6). 2018 PloS one Result HIV H69D 22 26 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In the context of SR2b, H69D demonstrated a phenotype like SR2a in that similar amounts of the FL precursor were detected with or without 5muM DRV. 2018 PloS one Result HIV H69D 24 28 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In the context of the SHC and SR2a fusions, H69D autoprocessing was mostly abolished (S3 Fig, lanes 27-30). 2018 PloS one Result HIV H69D 44 48 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In the light of different autoprocessing outcomes mediated by L-MBP vs C2-MBP fusion, we examined the possibility that H69D autoprocessing could also be differentially affected by the sequence upstream of p6*. 2018 PloS one Result HIV H69D 119 123 Gag 205 207 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. L-MBP fusion abolishes H69D autoprocessing. 2018 PloS one Result HIV H69D 23 27 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Meanwhile, the F56C/L63P produced more p6*-PRb fragment than the WT (Fig 7E) but had much less p6*-PRc than the WT (Fig 7F). 2018 PloS one Result HIV F56C;L63P 15;20 19;24 Gag;Gag 39;95 41;97 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Note that SR2a and SR2b differ by only one residue at position 8 (R8L in SR2a and R8P in SR2b) and SR2a is competent in MBP export but SR2b is not. 2018 PloS one Result HIV R8L;R8P 66;82 70;85 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. On the other hand, the inhibitory effect on H69D autoprocessing was maintained as similar levels of full length precursors were detected with or without 5muM DRV (lanes 29-32). 2018 PloS one Result HIV H69D 44 48 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. One of these is a substitution of the C-terminal p6* residue phenylalanine 56 (F56) for cysteine (C; F56C), which thereby alters the P1 residue at the PR N-terminal cleavage site. 2018 PloS one Result HIV F56C 101 105 Gag;PR 49;151 51;153 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Our data revealed that the mature PRs released from these L-MBP precursors remained readily detectable (Fig 2C, lanes 16-20) and H69D mutation also fully abolished autoprocessing activity of these precursors (Fig 2C, lanes 23, 26, 29). 2018 PloS one Result HIV H69D 129 133 PR 34 37 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. The D25N protease-deficient Flag-M1 precursor was autoprocessing deficient showing approximately equal amounts of unprocessed precursor with or without 5muM DRV (Fig 3C lanes 4, 5). 2018 PloS one Result HIV D25N 4 8 PR 9 17 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. The F56C/L63P double mutation produced less mature PR than the WT control (Fig 7C). 2018 PloS one Result HIV F56C;L63P 4;9 8;13 PR 51 53 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. The Flag-M1 precursor bearing the H69D mutation reproducibly exhibited partial activity (Fig 3C lanes 6, 7) as about 60% full-length precursor was detected without 5muM DRV compared to with 5muM DRV treatment. 2018 PloS one Result HIV H69D 34 38 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. The MBP SigP can also impede the H69D autoprocessing activity in a position-independent manner. 2018 PloS one Result HIV H69D 33 37 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. The released mature PRs were self-degradation resistant (Fig 4B, lanes 3-9) and H69D mutation abolished precursor autoprocessing as effectively as a D25N mutation (Fig 4C, lanes 21-28). 2018 PloS one Result HIV D25N;H69D 149;80 153;84 PR 20 23 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. The wild type control (Fig 7A and 7B, the upper panels) was compared to a F56C/L63P double mutation in the proviral context. 2018 PloS one Result HIV F56C;L63P 74;79 78;83 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Therefore, both proviral context and L-MBP fusion abolish H69D autoprocessing although the underlying mechanism remains to be defined. 2018 PloS one Result HIV H69D 58 62 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Therefore, the MBP SigP alone was sufficient to abolish H69D autoprocessing. 2018 PloS one Result HIV H69D 56 60 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. These results indicate that H69D autoprocessing is differentially affected by the L-MBP vs C2-MBP tag. 2018 PloS one Result HIV H69D 28 32 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. These two constructs also showed trace amounts of mature PR, but quantification analysis showed no difference in full-length precursor detection with or without 5muM DRV treatment, indicating that these H69D precursors were as inactive as they were when treated with 5 muM DRV. 2018 PloS one Result HIV H69D 203 207 PR 57 59 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. This double mutation displayed phenotypes resembling the F56C single mutation that supported normal Gag processing even with reduced mature PR production due to the suboptimal cleavage site rendered by the F56C mutation at the P1 position. 2018 PloS one Result HIV F56C;F56C 57;206 61;210 Gag;PR 100;140 103;142 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. This observation suggested that production of self-degradation resistant mature PR is not necessarily coupled with complete suppression of H69D autoprocessing. 2018 PloS one Result HIV H69D 139 143 PR 80 82 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. We also examined several H69D-containing precursors as another readout of autoprocessing modulation. 2018 PloS one Result HIV H69D 25 29 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. We also included H69Q as another control as it demonstrated wild type autoprocessing activity in our previous reports. 2018 PloS one Result HIV H69Q 17 21 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. We next asked whether the p6* peptide has a role in modulating H69D autoprocessing activity by testing L-MBP precursors with various p6* truncations. 2018 PloS one Result HIV H69D 63 67 Gag;Gag 26;133 28;135 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. We previously reported that H69D mutation completely suppresses PR autoprocessing in the context of a NL4-3 proviral construct but only partially inhibits precursor autoprocessing in the context of GST fusion. 2018 PloS one Result HIV H69D 28 32 PR 64 66 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Without SigP, H69D mutation partially suppressed precursor autoprocessing (Fig 5C, lanes 5, 6); with SigP, H69D abolished precursor autoprocessing as effectively as D25N (Fig 5C, lanes 9-12). 2018 PloS one Result HIV D25N;H69D;H69D 165;14;107 169;18;111 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. 6c, lane 4), but not in cells expressing Q65R, R77Q, R80A and Ct4RA. 2018 Retrovirology Result HIV Q65R;R77Q;R80A 41;47;53 45;51;57 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. 6d, right column), implying that the reduction of RPA70 loading was caused by defective chromatin remodelling by Q65R mutant. 2018 Retrovirology Result HIV Q65R 113 117 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. As both Q65R and Ct4RA were severely defective in Topo1-cc accumulation, the coordinated functions of Vpr were required for provoking such downstream events. 2018 Retrovirology Result HIV Q65R 8 12 Vpr 102 105 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Consistently, treatment with trichostatin A (TSA), a HDAC inhibitor that opens chromatin, successfully recovered RPA70 loading in the Q65R-expressing cells. 2018 Retrovirology Result HIV Q65R 134 138 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. For demonstrating the direct effects of virion-associated Vpr, we prepared lentiviral particles composed of defective integrase (IN-D64A) and Cherry-LacR-fused Vpr (CLV) or Cherry-Vpr (CV). 2018 Retrovirology Result HIV D64A 132 136 IN;Vpr;Vpr;Vpr;IN 118;58;160;180;129 127;61;163;183;131 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. In contrast, both Q65R and Ct4RA mutants increased RPA70 loading, but less potently than Vpr-Wt, which implies the dependence of RPA70 loading on the dual functional properties of Vpr; that is, DNA binding through the C-terminal region of Vpr and ubiquitination defective in the Q65R mutant. 2018 Retrovirology Result HIV Q65R;Q65R 18;279 22;283 Vpr;Vpr;Vpr 89;180;239 92;183;242 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. In contrast, the DSB level was not elevated in the Q65R and C-terminal mutants of Vpr. 2018 Retrovirology Result HIV Q65R 51 55 Vpr 82 85 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. In contrast, Vpr mutants (Q65R, R77Q and R80A) showed activities comparable with that of Vpr-Wt. 2018 Retrovirology Result HIV Q65R;R77Q;R80A 26;32;41 30;36;45 Vpr;Vpr 13;89 16;92 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. In striking contrast, the infection of CLV-Q65R virus, a lentivirus with Cherry-LacR fused to Vpr mutant of Q65R, did not induce the LacO-directed integration, indicating that Vpr-induced ubiquitination and DSB is required for these integrations. 2018 Retrovirology Result HIV Q65R;Q65R 43;108 47;112 Vpr;Vpr 94;176 97;179 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. In this experiment, we used IN-D64A mutant virus to exclude the effects of IN-dependent DSB. 2018 Retrovirology Result HIV D64A 31 35 IN;IN 28;75 30;77 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Moreover, this mobility change was reduced when H2B was mutated to a non-ubiquitinated form (K120R). 2018 Retrovirology Result HIV K120R 93 98 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Notably, other Vpr mutants, including Q65R, R77Q and R80A, showed similar activity with Vpr-Wt (Additional file 1: Figure S1c). 2018 Retrovirology Result HIV Q65R;R77Q;R80A 38;44;53 42;48;57 Vpr;Vpr 15;88 18;91 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Notably, the enhanced mobility of H2B-GFP was not detected in cells expressing the Q65R mutant. 2018 Retrovirology Result HIV Q65R 83 87 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Surprisingly, the Q65R mutant also increased psoralen binding to the LacO repeats. 2018 Retrovirology Result HIV Q65R 18 22 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. To test this notion, we monitored RPA70 loading with the Q65R/Ct4RA double mutant and observed that this mutant completely lost the ability to load RPA70. 2018 Retrovirology Result HIV Q65R 57 61 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Vpr-Wt significantly induced Topo1-cc accumulation on the LacO repeat region, whereas the Q65R and Ct4RA mutants did not. 2018 Retrovirology Result HIV Q65R 90 94 Vpr 0 3 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. A recent structural study of HIV-1 RTQ151M-complex suggested that the F116Y mutation improves polymerization fitness, which might be caused by N-site stabilization through hydrogen bond formation between the side-chain hydroxyl of Tyr116 and the main-chain O of Lys73. 2018 Scientific reports Result HIV Q151M;F116Y 37;70 42;75 RT 35 37 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. After mixing RTQ151M and the DNA aptamer, gel-filtration chromatography was applied to separate unbound DNA and the RTQ151M:DNA complex. 2018 Scientific reports Result HIV Q151M;Q151M 15;118 20;123 RT;RT 13;116 15;118 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Although single Q151M substitution leads to a drastic increase in ETV sensitivity, the current structure of the ternary complex revealed no direct interactions between the Met151 side-chain and the exocyclic methylene of ETV-TP. 2018 Scientific reports Result HIV Q151M 16 21 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Because the amino acid residues forming the N-site are identical between HIV-1 and HIV-2 RT, similar mechanisms, i.e., N-site perturbation and increased hydrophobicity caused by the Q151M mutation, likely underlie the AZT resistance of HIV-2 RTQ151M. 2018 Scientific reports Result HIV Q151M;Q151M 244;182 249;187 RT;RT 89;242 91;244 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Consequently, the present structure of the RTQ151M:DNA binary complex exhibits a more open conformation than that of the previously reported RTWT:DNA structure. 2018 Scientific reports Result HIV Q151M 45 50 RT 43 45 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Considering the results of the viral replication and antiviral assays, we reasoned that HIV-1 RTQ151M would be a suitable candidate for crystallographic study to elucidate the HIV-1 RT N-site structure in the ETV-TP binding state. 2018 Scientific reports Result HIV Q151M 96 101 RT;RT 94;182 96;184 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Critically, EFdA activity against HIV-1Q151M and HIV-1Q151M/Y115F/F116Y increased (IC50: 30 pM for both variants) when compared to that against HIV-1WT (IC50: 0.4 nM). 2018 Scientific reports Result HIV F116Y;Y115F 66;60 71;65 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Crystal structure analysis of HIV-2 RTQ151M:DNA:NRTI would be needed to discuss the NRTI-resistance mechanism of HIV-2 RT more precisely. 2018 Scientific reports Result HIV Q151M 38 43 NRTI;NRTI;RT;RT 48;84;36;119 52;88;38;121 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Definitive structural differences between HIV-1 RTQ151M and HBV RT likely exist, because HIV-1 RTQ151M exhibits high sensitivity to both ETV and EFdA. 2018 Scientific reports Result HIV Q151M;Q151M 50;97 55;102 RT;RT;RT 48;64;95 50;66;97 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. For crystallization of the RTQ151M:DNA binary complex, the previously developed 38-mer DNA aptamer was applied, albeit with 3 base substitutions to trap guanosine analogue ETV-TP at the N-site. 2018 Scientific reports Result HIV Q151M 29 34 RT 27 29 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. For example, Q151M confers resistance against AZT by 5-fold. 2018 Scientific reports Result HIV Q151M 13 18 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Furthermore, the anti-HIV-1 activity of ETV drastically improved in the presence of Q151M and additional mutations Y115F and F116Y; the IC50 numbers of ETV against HIV-1Q151M and HIV-1Q151M/Y115F/F116Y decreased to 42 nM and 13 nM, respectively (26-fold and 85-fold less than that of HIV-1WT). 2018 Scientific reports Result HIV F116Y;Y115F;F116Y;Q151M;Y115F 196;190;125;84;115 201;195;130;89;120 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Gln/Met151 is located at the entrance of the N-site and likely acts as a lid. 2018 Scientific reports Result HIV Q151M 0 10 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. HIV-1 RT M184V was also detected from HIV-HBV co-infected patients receiving ETV monotherapy, and in vitro experiments further demonstrated that M184V of HIV-1 RT confers resistance to ETV. 2018 Scientific reports Result HIV M184V;M184V 9;145 14;150 RT;RT 6;160 8;162 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. HIV-1Q151M, HIV-1Q151M/Y115F/F116Y, and HIV-1Q151M/I63V/L74V propagated slower than did HIV-1WT, but HIV-1Q151M/Y115F/F116Y reached similar or slightly greater supernatant p24 levels on day 9 than did HIV-1WT. 2018 Scientific reports Result HIV F116Y;F116Y;L74V;Y115F;Y115F 29;118;56;23;112 34;123;60;28;117 p24 172 175 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. I63V/L74V thus weaken the stabilization of bound ETV-TP at the N-site, which might drastically decrease ETV-MP incorporation into primer DNA. 2018 Scientific reports Result HIV L74V 5 9 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. In contrast to Y115F/F116Y, the I63V/L74V mutations markedly decreased ETV sensitivity. 2018 Scientific reports Result HIV F116Y;L74V;Y115F 21;37;15 26;41;20 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. In contrast, the propagation of HIV-1Q151M/G112S/D113A was relatively slow, with a day 9 viral level approximately 40% that of HIV-1WT. 2018 Scientific reports Result HIV G112S 43 48 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. In recent structural studies of the HIV-1 RTQ151M and RTQ151M-complex, a multi-NRTI resistance mechanism was proposed: the Q151M mutation increases the perturbation of the N-site by removal of the hydrogen bond between Gln151 and Arg72, leading to decreased incorporation of 3'-exo-forming dideoxy NRTIs. 2018 Scientific reports Result HIV Q151M;Q151M;Q151M 44;56;123 49;61;128 NRTI;NRTI;RT;RT 79;298;42;54 83;303;44;56 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. In RTWT structures, a hydrogen bond is formed between the side-chain of Gln151 and Arg72, whereas the thioether group of Met151 in the RTQ151M structures occupies roughly the same position as Gln151 but keeps the distances of van der Waals contacts with nearby Arg72, Phe115, and C2' of dGTP/ETV-TP (3.6-4.0 A). 2018 Scientific reports Result HIV Q151M 137 142 RT 135 137 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. It should also be noted that Q151M is widely known as a multi-NRTI-resistant mutation in HIV-1 RT, as described later. 2018 Scientific reports Result HIV Q151M 29 34 NRTI;RT 62;95 66;97 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Native polyacrylamide gel electrophoresis (PAGE) analysis showed that the peak fractions contained no DNA-free RTQ151M, indicating that the RTQ151M:DNA was stable and well equilibrated. 2018 Scientific reports Result HIV Q151M;Q151M 113;142 118;147 RT;RT 111;140 113;142 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Next, we examined the antiviral activity of these NRTIs against HIV-1Q151M, HIV-1Q151M/Y115F/F116Y, and HIV-1Q151M/I63V/L74V. 2018 Scientific reports Result HIV F116Y;L74V;Y115F 93;120;87 98;124;92 NRTI 50 55 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Notably, mutations including Q151M and some accessory mutations are also reportedly cause intermediate-level resistance to 3TC and TDF; however, such resistance was not caused by any variants tested in this study (Table 2). 2018 Scientific reports Result HIV Q151M 29 34 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Notably, Q151M also intensified sensitivity against EFdA by approximately 13-fold. 2018 Scientific reports Result HIV Q151M 9 14 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Notably, Q151M is also an important AZT-resistant mutation to HIV-2 RT. 2018 Scientific reports Result HIV Q151M 9 14 RT 68 70 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Notably, the magnitude of enzymatic activity of RTQ151M was almost identical to that of RTWT (Supplementary Table S1), and further investigation will be needed to explain the slight difference between HIV-1 RT activity and the propagation profile of HIV-1 with the Q151M mutation. 2018 Scientific reports Result HIV Q151M;Q151M 50;265 55;270 RT;RT 48;207 50;209 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Of these 8 mutation candidates, we reasoned that substitution of the hydrophilic Gln151 for the bulky and hydrophobic methionine (Q151M) would be the most significant, while the remaining 7 candidates were categorized as mutations with similar side-chain properties. 2018 Scientific reports Result HIV Q151M 130 135 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Quantitation by polymerase chain reaction (PCR) using viral supernatant of 293 T cells showed that RTQ151M activity was approximately 77% that of RTWT (Supplementary Table S1). 2018 Scientific reports Result HIV Q151M 101 106 Pol;RT 16;99 26;101 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Recombinant HIV-1 RTWT and RTQ151M were produced by Escherichia coli and purified by Ni-affinity and ion-exchanging chromatography (see Methods). 2018 Scientific reports Result HIV Q151M 29 34 RT 27 29 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. reported, HIV-1 RT Q151M, known as a multi-NRTI-resistant mutation, usually occurs in combination with accessory mutations, including A62V, V75I, F77L, and F116Y (Q151M-complex). 2018 Scientific reports Result HIV F116Y;F77L;Q151M;Q151M 156;146;19;163 161;150;24;168 NRTI;RT 43;16 47;18 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. RTQ151M:DNA:dGTP and RTQ151M:DNA:ETV-TP ternary complex crystals were prepared by soaking the crystals of the binary complex in the crystallization mother liquor supplemented with dGTP/ETV-TP. 2018 Scientific reports Result HIV Q151M;Q151M 2;23 7;28 RT;RT 0;21 2;23 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Structural description of the RTQ151M N-site occupied by ETV-TP. 2018 Scientific reports Result HIV Q151M 32 37 RT 30 32 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Structure determination of RTQ151M binary and ternary complex. 2018 Scientific reports Result HIV Q151M 29 34 RT 27 29 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Taken together, the results implied that the F160L mutation was exceptionally harmful to viral replication. 2018 Scientific reports Result HIV F160L 45 50 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The antiviral assay revealed that the Y115F and F116Y mutations increased the ETV sensitivity of HIV-1Q151M by 3-fold. 2018 Scientific reports Result HIV F116Y;Y115F 48;38 53;43 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The Q151M-complex causes high-level resistance to AZT and certain NRTIs with the dideoxy configuration, such as ddC and ddI. 2018 Scientific reports Result HIV Q151M 4 9 NRTI 66 71 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The RT assay for the purified sample by enzyme-linked immune-sorbent analysis (ELISA) demonstrated that RTQ151M and RTWT showed similar activity levels (Supplementary Table S1). 2018 Scientific reports Result HIV Q151M 106 111 RT;RT 4;104 6;106 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The same observations have also been made in the recently reported structures of HIV-1 RTQ151M and RTQ151M-complex ternary complexes. 2018 Scientific reports Result HIV Q151M;Q151M 89;101 94;106 RT;RT 87;99 89;101 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The same stabilization effect is expected when ETV-TP is bound to the N-site of HIV-1 RTQ151M/Y115F/F116Y, thus leading to the increase of ETV sensitivity. 2018 Scientific reports Result HIV Q151M;F116Y;Y115F 88;100;94 93;105;99 RT 86 88 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The structural information on HIV-1 RTQ151M together with the results of the antiviral assays enable us to further discuss the individual role of each amino acid residue at or near the N-site in affecting NRTI sensitivity and resistance. 2018 Scientific reports Result HIV Q151M 38 43 NRTI;RT 205;36 209;38 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The structure of the RTQ151M:DNA binary complex was determined by molecular replacement with the previously reported RTWT:DNA binary complex (PDB code, 5D3G) as a search model and refined to 2.6 A resolution. 2018 Scientific reports Result HIV Q151M 23 28 RT 21 23 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The structures of the RTQ151M:DNA:dGTP and RTQ151M:DNA:ETV-TP ternary complexes were determined at 2.38 A and 2.45 A resolution, respectively. 2018 Scientific reports Result HIV Q151M;Q151M 24;45 29;50 RT;RT 22;43 24;45 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. The structures reported in this work have been determined in the rhombohedral lattice system for the first time, whereas the structures of RTQ151M:DNA:dGTP/ETV-TP basically exhibit a typical closed conformation of the HIV-1 RT ternary complex, and thus superimpose well on previously reported structures of the dNTP/NRTI ternary complex with main-chain RMSD of ~1.2 A. 2018 Scientific reports Result HIV Q151M 141 146 NRTI;RT;RT 316;139;224 320;141;226 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Their replication kinetics suggested that although HIV-1Q151M/F160L completely failed to replicate when cultured up to 9 days, the other 4 variants successfully propagated. 2018 Scientific reports Result HIV F160L 62 67 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. There are two RTQ151M heterodimers (p66/p51) in the asymmetric unit of the rhombohedral R3 lattice. 2018 Scientific reports Result HIV Q151M 16 21 RT 14 16 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. These results indicated that the Q151M mutation does not significantly affect the enzymatic activity of HIV-1 RT. 2018 Scientific reports Result HIV Q151M 33 38 RT 110 112 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. These structural aspects as well as the results of antiviral assays strongly suggest that Q151M contributes not to the tight binding of ETV-TP to the N-site as observed in the crystal structure analysis, but to the process of ETV-TP entry into the N-site. 2018 Scientific reports Result HIV Q151M 90 95 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. This suggested that the Q151M mutation was strongly associated with ETV-TP binding to the N-site of HIV-1 RT, with additional Y115F/F116Y mutations further enhancing the ETV sensitivity of HIV-1Q151M. 2018 Scientific reports Result HIV F116Y;Q151M;Y115F 132;24;126 137;29;131 RT 106 108 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Unfortunately, HIV-1 could not be propagated upon introduction of the F160L mutation. 2018 Scientific reports Result HIV F160L 70 75 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We chose 3 well-replicable variants (HIV-1Q151M, HIV-1Q151M/Y115F/F116Y, and HIV-1Q151M/I63V/L74V) for the antiviral assay, and investigated whether these HBV RT-mimicking mutations could change sensitivities against the typical anti-HBV/HIV-1 NRTIs. 2018 Scientific reports Result HIV F116Y;L74V;Y115F 66;93;60 71;97;65 NRTI;RT 244;159 249;161 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We confirmed that HIV-1Q151M also caused moderate-level resistance to AZT (~5-fold); the combination of Q151M and F116Y decreased AZT sensitivity further, as expected (IC50: 0.2 muM) (Table 2). 2018 Scientific reports Result HIV F116Y;Q151M 114;104 119;109 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We created 5 HBV RT-mimicking HIV-1 RT mutants in this study: RTQ151M, RTQ151M/F160L, RTQ151M/G112S/D113A, RTQ151M/Y115F/F116Y, and RTQ151M/I63V/L74V (Table 1). 2018 Scientific reports Result HIV Q151M;Q151M;Q151M;F116Y;G112S;L74V;Y115F;Q151M;Q151M;F160L 88;109;134;121;94;145;115;64;73;79 93;114;139;126;99;149;120;69;78;84 RT;RT;RT;RT;RT;RT;RT 17;36;62;71;86;107;132 19;38;64;73;88;109;134 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We further propose the additional possibility that Gln/Met151 plays a role as a selector in response to the hydrophobicity of incoming NRTI. 2018 Scientific reports Result HIV Q151M 49 61 NRTI 135 139 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We speculate that the hydrophobic pocket of HIV-1 RT accommodating the unique 4'-ethynyl group of EFdA may be distorted or destroyed by F160L and neighboring G112S/D113A mutations, leading to the preclusion of EFdA-TP binding to the N-site of HBV RT. 2018 Scientific reports Result HIV F160L;G112S 136;158 141;163 RT;RT 50;247 52;249 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. NGS showed a previously undetected G73D mutation (frequency 10%), predicted to confer resistance to saquinavir. 2018 Journal of clinical virology Result HIV G73D 35 39 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. Notably, I50L was not detected as a minority variant at this time point despite its detection (as a mixture) by Sanger sequencing at week 48, and it was also absent by Sanger sequencing at week 71. 2018 Journal of clinical virology Result HIV I50L 9 13 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. Patient A, who received atazanavir as PI monotherapy, met the primary outcome due to an I50L mutation (patient 5 in Table 2 in main trial report). 2018 Journal of clinical virology Result HIV I50L 88 92 PI 38 40 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. The L89V mutation (frequency 5%), which predicts resistance to fosamprenavir, was detected at 41 weeks in patient C. 2018 Journal of clinical virology Result HIV L89V 4 8 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. The virus of patient B, who received darunavir monotherapy, expressed the I54T mutation (frequency 2%) at 48 weeks. 2018 Journal of clinical virology Result HIV I54T 74 78 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. 1) contained the V32I substitution, although other substitutions such as L10F, L33F, M46I, A71V, and I84V had been acquired in a subset of the six clones. 2018 mBio Result HIV A71V;I84V;L10F;L33F;M46I;V32I 91;101;73;79;85;17 95;105;77;83;89;21 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. 1A), followed by rHIVV32I/I54M and rHIVL33F/I84V, which vigorously replicated in the presence of 1 muM DRV by the end of 22 and 26 weeks of selection, respectively. 2018 mBio Result HIV I54M;I84V;L33F 26;44;39 30;48;43 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. 1B), had acquired only K43T, whose significance in the development of PI resistance is well-known. 2018 mBio Result HIV K43T 23 27 PI 70 72 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. 2B, V32I was not seen in any of the 20 clones examined for HIVWT-WK50 and HIVL33F-WK50, suggesting that the emergence of V32I might have been associated with the eventual development of DRV resistance in the 6 clones described above. 2018 mBio Result HIV L33F;V32I;V32I 77;4;121 81;8;125 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. A newly generated infectious clone, rHIVDRVRP51I32V, in which the substitution V32I was reverted back to Val, was found to be only moderately resistant to DRV with an IC50 of 29 nM. 2018 mBio Result HIV V32I 79 83 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. A71V predisposes HIV-1 to its acquisition of high-level DRV resistance. 2018 mBio Result HIV A71V 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. As expected, rHIVV32I/L33F/I54M/I84V proved to be highly resistant to DRV with an IC50 of 639 nM, while rHIVL33F, rHIVI54M, and rHIVI84V were as sensitive as rHIVWT with IC50s of ~3 nM, virtually identical to that of rHIVWT, in line with our previous report. 2018 mBio Result HIV I54M;I84V;L33F 27;32;22 31;36;26 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. As previously reported, the highly DRV-resistant HIV-1 variant, HIVDRVRP51, contains four major DRV resistance-associated amino acid substitutions (V32I, L33F, I54M, and I84V) in its protease, which are responsible for the loss of DRV's protease dimerization inhibition activity. 2018 mBio Result HIV I54M;I84V;L33F;V32I 160;170;154;148 164;174;158;152 PR;PR 183;237 191;245 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Furthermore, when the A71V substitution is combined with V32I and I54M or V32I and I84V (both of which by themselves appear to be hypersensitive on their own), the resultant HIV-1 yields high-level DRV resistance (Table 2). 2018 mBio Result HIV A71V;I54M;I84V;V32I;V32I 22;66;83;57;74 26;70;87;61;78 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. HIVWT examined at week 50 of selection (HIVWT-WK50) had acquired three substitutions, M46L, K55N, and V82I, by 50 weeks. 2018 mBio Result HIV K55N;M46L;V82I 92;86;102 96;90;106 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. However, the addition of A71V to these two clones, generating rHIVV32I/I54M/A71V and rHIVV32I/A71V/I84V, acquired significant resistance to DRV with their IC50s of 27 and 35 nM, respectively (Table 2). 2018 mBio Result HIV A71V;A71V;I54M;I84V;V32I;A71V 76;94;71;99;89;25 80;98;75;103;93;29 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Interestingly, the addition of A71V substitution to rHIVV32I clearly mitigated the compromised replication fitness of rHIVV32I. 2018 mBio Result HIV A71V 31 35 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It is noteworthy that rHIVV32I was hypersensitive to DRV with an IC50 of 0.2 nM, 16.7-fold more sensitive to DRV compared to rHIVWT (Table 1), suggesting that since the emergence of DRV-hypersensitive HIVV32I would be prohibitive in the presence of DRV, rHIVWT is not likely to directly acquire V32I substitution. 2018 mBio Result HIV V32I 295 299 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It is possible that the presence of A71V might predispose to HIV-1's acquisition of V32I. 2018 mBio Result HIV A71V;V32I 36;84 40;88 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It was also noted that in five of the six clones, A71V had emerged in quite early stages of DRV selection (by the end of 5 to 8 weeks of selection), followed by the emergence of V32I substitution. 2018 mBio Result HIV A71V;V32I 50;178 54;182 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It was noteworthy that all six clones that eventually developed DRV resistance (HIVV32I/L33F/I54M/I84V-WK17, HIVV32I/I54M-WK22, HIVL33F/I84V-WK26, HIVI84V-WK29, HIVV32I-WK36, and HIVI54M-WK36). 2018 mBio Result HIV I54M;I84V;L33F;I54M;I54M;I84V;I84V 93;98;88;117;182;136;150 97;102;92;121;186;140;154 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Overall, the Connolly surface interactions suggested better interactions of DRV with both Ile32 and Ile32' of V32I-substituted protease (PRV32I) than with Val32 and Val32' of PRWT. 2018 mBio Result HIV V32I 110 114 PR;PR 127;137 135;139 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Since the M46I substitution is often seen in various PI-resistant HIV-1 variants and that substitution was also seen in the present study. 2018 mBio Result HIV M46I 10 14 PI 53 55 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Since the presence of A71V might predispose HIV-1 to its acquisition of V32I as discussed above, we generated various recombinant infectious HIV-1 clones and determined their susceptibility to DRV (Table 2). 2018 mBio Result HIV A71V;V32I 22;72 26;76 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. suggesting that V32I substitution might have played an important role in the pathway of DRV resistance development. 2018 mBio Result HIV V32I 16 20 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The addition of A71V to rHIVV32I that was hypersensitive to DRV (IC50 = 0.2 nM), generating rHIVV32I/A71V, abrogated the DRV hypersensitivity of rHIVV32I to DRV and the IC50 of rHIVV32I/A71V became virtually the same as that of rHIVWT (2.8 versus 3.1 nM). 2018 mBio Result HIV A71V;A71V;A71V 16;101;186 20;105;190 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The V32I substitution increases van der Waals interactions with DRV. 2018 mBio Result HIV V32I 4 8 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The V32I substitution predisposes HIV-1 to acquisition of DRV resistance. 2018 mBio Result HIV V32I 4 8 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These data strongly suggest that the presence of A71V predisposes HIV-1 to its acquisition of V32I in the pathway toward HIV-1's acquisition of high-level DRV resistance at least when rHIVWT (HIV-1NL4-3) was employed as a starting viral population in the selection with DRV. 2018 mBio Result HIV A71V;V32I 49;94 53;98 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These data strongly suggest that while the A71V substitution by itself confers no particular DRV resistance on HIV-1, combining it with the V32I substitution appears to suppress the hypersusceptibility phenotype conferred by V32I substitution and retains the wild-type level of susceptibility of rHIVA71V:as if the effect of V32I substitution were suppressed. 2018 mBio Result HIV A71V;V32I;V32I;V32I 43;140;225;325 47;144;229;329 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These data strongly suggested that the order of the magnitude of contribution to the high-level DRV resistance was V32I I84V > I54M >> L33F. 2018 mBio Result HIV I54M;I84V;L33F;V32I 129;122;137;115 133;126;141;119 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These data suggest that the presence of A71V enables and probably accelerates the emergence of V32I. 2018 mBio Result HIV A71V;V32I 40;95 44;99 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Two clones, rHIVV32I/I54M and rHIVV32I/I84V, were also found hypersensitive to DRV with IC50s of 1.7 and 0.42 nM, suggesting that these two clones would not emerge in the presence of DRV. 2018 mBio Result HIV I54M;I84V 21;39 25;43 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. V32I compromises the replication fitness of rHIVWT, but the addition of A71V mitigates the compromised fitness. 2018 mBio Result HIV A71V;V32I 72;0 76;4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. V32I increases DRV's protease dimerization inhibition and reduces viral fitness. 2018 mBio Result HIV V32I 0 4 PR 21 29 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. V32I renders rHIVWT highly susceptible to DRV. 2018 mBio Result HIV V32I 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We further attempted to examine the replication kinetics of three infectious clones, rHIVWT, rHIVV32I, and rHIVV32I/A71V in the presence or absence of DRV. 2018 mBio Result HIV A71V 116 120 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We further attempted to examine whether the addition of A71V to rHIVWT, generating rHIVA71V, renders rHIVWT inclined to eventually develop high-level DRV resistance. 2018 mBio Result HIV A71V 56 60 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We subsequently introduced all four substitutions or each single substitution into HIVNL4-3 (rHIVWT), generating rHIVV32I/L33F/I54M/I84V, rHIVV32I, rHIVL33F, rHIVI54M, and rHIVI84V. 2018 mBio Result HIV I54M;I84V;L33F 127;132;122 131;136;126 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We then analyzed the interactions of V32I mutant protease (PRV32I) with DRV. 2018 mBio Result HIV V32I 37 41 PR;PR 49;59 57;61 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. We, therefore, further asked whether the two clones that did not develop DRV resistance by the end of 50 weeks of selection (HIVWT-WK50 and HIVL33F-WK50) had not acquired V32I. 2018 mBio Result HIV L33F;V32I 143;171 147;175 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. When three such recombinant clones (rHIVV32I/L33F/I54M/I84V, rHIVV32I/I54M, and rHIVL33F/I84V) were propagated in increasing concentrations of DRV, rHIVV32I/L33F/I54M/I84V readily acquired high-level DRV resistance and replicated in the presence of 5 muM DRV by 17 weeks of selection. 2018 mBio Result HIV I54M;I54M;I84V;I84V;L33F;L33F;I54M;I84V 50;162;55;167;45;157;70;89 54;166;59;171;49;161;74;93 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. After adjustment for multiple comparison, K103N was the only mutation associated with significant cross-resistance to RPV from individuals on failing NNRTI therapy at the q < 0.15 cutoff (p < 0.001) (Table 2). 2018 Antiviral chemistry & chemotherapy Result HIV K103N 42 47 NNRTI 150 155 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. As expected, the 19 of 55 (34%) samples with K103N and no RPV-associated mutations had relatively low FC values (median 2.6, IQR 1.4-4.2). 2018 Antiviral chemistry & chemotherapy Result HIV K103N 45 50 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. By contrast, K103N in combination with one or two other RPV-associated mutations (including mutations at codons 100, 101, 138, 179, 181, 188, 221, 227 and/or 230) had a significantly higher median FC than samples with RPV-associated mutations without K103N (p <= 0.01). 2018 Antiviral chemistry & chemotherapy Result HIV K103N;K103N 13;251 18;256 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Fifty-five of 100 samples had HIV-1 genotypes that included K103N. 2018 Antiviral chemistry & chemotherapy Result HIV K103N 60 65 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. However, four out of four samples with K103N as the only NNRTI mutation were susceptible to RPV (FC range 0.9 to 2.0), indicating that additional resistance mutations were necessary for the reduction in RPV susceptibility conferred by K103N (Supplementary Table S1). 2018 Antiviral chemistry & chemotherapy Result HIV K103N;K103N 39;235 44;240 NNRTI 57 62 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. In the absence of RPV mutations, a similar trend of higher levels of FC is observed with the addition of K103N with two or more NNRTI mutations, but the numbers were too small to achieve statistical significance. 2018 Antiviral chemistry & chemotherapy Result HIV K103N 105 110 NNRTI 128 133 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. L100I, V108I and Y181C also showed a trend toward increased cross-resistance, but when adjusted for multiple comparisons, these were no longer significant. 2018 Antiviral chemistry & chemotherapy Result HIV V108I;Y181C;L100I 7;17;0 12;22;5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. No other RPV-associated mutations in this sample set including K101E, E138A/K, V179I/L, Y188L, G190A, M230L, H221Y or F227C were associated with RPV cross-resistance (Table 2). 2018 Antiviral chemistry & chemotherapy Result HIV E138A;E138K;F227C;G190A;H221Y;K101E;M230L;V179I;V179L;Y188L 70;70;118;95;109;63;102;79;79;88 77;77;123;100;114;68;107;86;86;93 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. The combination of K103N with other NNRTI resistance mutations was explored for its role in conferring cross-resistance to RPV. 2018 Antiviral chemistry & chemotherapy Result HIV K103N 19 24 NNRTI 36 41 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. The number of RPV mutations per sample was associated with increased RPV resistance (p < 0.05) and the addition of K103N significantly enhanced the FC (p < 0.001) (Figure 2). 2018 Antiviral chemistry & chemotherapy Result HIV K103N 115 120 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. At 52 and 61 days post-infection, 8 of 21 (38.1%) and 5 of 9 (55.6%) pol sequences from plasma contained the nonsynonymous M184V mutation, respectively. 2018 PLoS medicine Result HIV M184V 123 128 Pol 69 72 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. In the first of our post-hoc analyses, in which we considered only the 25 partner-pairs in which the direction of transmission could be determined and used the 1% threshold, we observed one G73S in both the transmitter and recipient partner out of 13 low-frequency mutations identified in known transmitters (7.7%, exact 95% CI 0.19%-36.0%), with an expected likelihood of identifying one or more mutations in recipients of 32.3%. 2018 PLoS medicine Result HIV G73S 190 194 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. Longitudinal analysis of PIC90629 by SGA confirmed 454-pyrosequencing results and identified a mixture of M184M/V. 2018 PLoS medicine Result HIV M184M;M184V 106;106 113;113 PI 25 27 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. The majority (92.6%) of all 27 low-frequency mutations identified in our study were detected in PBMCs, and many were consistent with APOBEC mutations (e.g., M184I and G73S) or regions of homopolymers, such as K101E and K219Q (Tables 2 and 3). 2018 PLoS medicine Result HIV G73S;K101E;K219Q;M184I 167;209;219;157 171;214;224;162 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. The observed frequencies of M184M/V in PIC90629 raised the possibility that at least two HIV variants founded infection in this individual. 2018 PLoS medicine Result HIV M184M;M184V 28;28 35;35 PI 39 41 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. Two (14%, 95% CI, 1.8%-42.8%) G73S accessory mutations were detected in the PBMCs of the recipient at a level of 1.1% and either 1.0%/1.2% or 2.0%, depending on who was considered the transmitter and recipient among partner-pair #5. 2018 PLoS medicine Result HIV G73S 30 34 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. 3A, left side), where a trend toward reduced levels of captured mutant RT co-IP was observed, especially for E300A. 2018 mBio Result HIV E300A 109 114 RT 71 73 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. 5A), where infectivity was significantly lower for E300R mutant HIV-1. 2018 mBio Result HIV E300R 51 56 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. 7B) T cells, whereas E298R and E300R mutant HIV-1 had significantly less replication. 2018 mBio Result HIV E298R;E300R 21;31 26;36 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. 7B) than the WT and E297R or E298R mutant viruses. 2018 mBio Result HIV E297R;E298R 20;29 25;34 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. A known RT heterodimer inhibitory mutation, L234A, substantially reduced the MAPPIT luciferase signal below that of the WT RT heterodimer interaction. 2018 mBio Result HIV L234A 44 49 RT;RT 8;123 10;125 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. A WT and E300R mutant RT heterodimer was purified from Escherichia coli by previously described methods, and Coomassie stain analysis indicated that the purified proteins were free of contaminants. 2018 mBio Result HIV E300R 9 14 RT 22 24 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. An interpretation of the reduced infectivity of E298R is complicated, as this virus had less in vitro RT catalytic activity than the others. 2018 mBio Result HIV E298R 48 53 RT 102 104 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Before this, a cell-based system called mammalian protein-protein interaction trap (MAPPIT) was used to determine if the E300R mutation affects RTp51 and RTp66 heterodimerization, which induces luciferase expression in the MAPPIT system as previously described. 2018 mBio Result HIV E300R 121 126 RT;RT 144;154 146;156 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Between 60 and 80% of the cores had completed uncoating by 1 h postinfection for WT HIV-1 and all of the HIV-1 mutants tested (E297R, E298R, and E300R). 2018 mBio Result HIV E297R;E298R;E300R 127;134;145 132;139;150 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Calculations of changes in the thermodynamic stability of the RT heterodimer caused by RTp66 mutagenesis were performed by using the empirical force field FoldX program, which showed that the W252A and L303A mutations are severely destabilizing. 2018 mBio Result HIV L303A;W252A 202;192 207;197 RT;RT 62;87 64;89 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Furthermore, the W252A and L303A mutations were predicted to greatly reduce the frequency of the salt bridge between E298 and K281 and also alter the hydrogen bonding pattern of several surface-exposed electrically charged residues in the thumb domain. 2018 mBio Result HIV L303A;W252A 27;17 32;22 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Hence, expression of either WT RT subunit can rescue the co-IP of the counterpart E300R mutant RT heterodimer subunit. 2018 mBio Result HIV E300R 82 87 RT;RT 31;95 33;97 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 assembly, packaging, maturation, in vitro RT catalytic activity, and ERT are unaffected by the E300R RT mutation. 2018 mBio Result HIV E300R 101 106 RT;RT 48;107 50;109 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 containing each of the E297R, E298R, and E300R mutations had fewer copies of ssDNA, first strand transfer DNA, and late-stage DNA at 4 h postinfection than WT HIV-1 (Table 1). 2018 mBio Result HIV E297R;E298R;E300R 29;36;47 34;41;52 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 containing the E298R and E300R mutations had delayed uncoating kinetics compared to those of WT and E297R mutant HIV-1, with 10 and 20% fewer cells with uncoated cores between 30 and 60 min postinfection, respectively. 2018 mBio Result HIV E297R;E298R;E300R 106;21;31 111;26;36 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 with the E298R and E300R RT mutations has impaired infectivity, delayed reverse transcription, and reduced reverse transcription efficiency in HeLa cells. 2018 mBio Result HIV E298R;E300R 15;25 20;30 RT;RT;RT 78;113;31 99;134;33 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 with the E298R mutation had approximately half the amount of HIV-1 produced and released into cell culture supernatant at the time point of peak HIV-1 viremia. 2018 mBio Result HIV E298R 15 20 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 with the E298R or E300R RT mutation has delayed uncoating kinetics in cells. 2018 mBio Result HIV E298R;E300R 15;24 20;29 RT 30 32 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 with the E298R or E300R RT mutation has reduced replication in Jurkat cells, CD4+ T cells, and TZM-bl cells. 2018 mBio Result HIV E298R;E300R 15;24 20;29 RT 30 32 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 with the E300R mutation had more delayed uncoating kinetics (50%) than the E298R mutant (20%), despite the reduced in vitro RT catalytic activity and reverse transcription completion kinetics of E298R mutant HIV-1. 2018 mBio Result HIV E298R;E298R;E300R 81;201;15 86;206;20 RT;RT 156;130 177;132 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. HIV-1 with the RT E300R mutation had 10 to 30% less reverse transcription completion between 3 and 6 h postinfection than the WT. 2018 mBio Result HIV E300R 18 23 RT;RT 52;15 73;17 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. However, the E298R and E300R mutations significantly reduced the interaction with recombinant eEF1A by 40 and 70% compared to WT RT, respectively. 2018 mBio Result HIV E298R;E300R 13;23 18;28 RT 129 131 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. However, the E300R mutant RTp51/p66 heterodimer dissociation rate constant was approximately 3-fold higher than that of the WT protein. 2018 mBio Result HIV E300R 13 18 RT 26 28 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. However, the E300R mutation had significantly (P < 0.05) reduced HIV-1 infectivity, even though RT in vitro catalytic activity and ERT were unaffected. 2018 mBio Result HIV E300R 13 18 RT 96 98 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. However, when WT RTp51 was cotransfected with E300R mutant RTp66 or E300R mutant RTp51 was cotransfected with WT RTp66, both RT subunits were coimmunoprecipitated with eEF1A. 2018 mBio Result HIV E300R;E300R 46;68 51;73 RT;RT;RT;RT;RT 17;59;81;113;125 19;61;83;115;127 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. In comparison, E297R mutant HIV-1NL4.3-Deltaenv-eGFP had increased RT catalytic activity in vitro; however, its infectivity was not significantly different from that of the WT virus. 2018 mBio Result HIV E297R 15 20 RT 67 69 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. In silico simulations reveal that the W252A and L303A mutations disrupt a surface-exposed acidic patch of residues in the alpha-J helix and flanking regions of the HIV-1 RT thumb domain. 2018 mBio Result HIV L303A;W252A 48;38 53;43 RT 170 172 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. It is unclear whether the beta-strand-like conformation of the peptide backbone across residues 250 to 253 or increased flexibility in the unstructured loop spanning residues 244 to 249 has any specific importance in the interaction of RT with eEF1A; however, it is a clear marker of more widespread structural changes in the W252A, L303A, and E298R mutations compared to E300R in our molecular dynamic simulations. 2018 mBio Result HIV E298R;E300R;L303A;W252A 344;372;333;326 349;377;338;331 RT 236 238 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Luciferase expression was similar between the cotransfection of both WT RT heterodimer subunits and both E300R mutant RT heterodimer subunits, indicating that RTp51 and RTp66 heterodimerization was not affected by the E300R mutation. 2018 mBio Result HIV E300R;E300R 105;218 110;223 RT;RT;RT;RT 72;118;159;169 74;120;161;171 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Molecular dynamic simulations supported the FoldX results in that the E298R mutation (but not the E300R mutation) disrupted the peptide backbone across residues 250 to 253, similarly to the W252A and L303A mutations, and thereby caused a substantial redistribution of the positive and negative charges on the surface of the thumb domain. 2018 mBio Result HIV E298R;E300R;L303A;W252A 70;98;200;190 75;103;205;195 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Mutation of the individual D250, E297, E298, or E300 residue to arginine produced a reduced level of coimmunoprecipitated RT, and the E300R mutation caused the most defective interaction with eEF1A. 2018 mBio Result HIV E300R 134 139 RT 122 124 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. NanoBRET also confirmed that RTp66 with the L303A mutation had a reduced interaction with recombinant eEF1A. 2018 mBio Result HIV L303A 44 49 RT 29 31 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Our previous study indicated that the W252A and L303A mutations reduce the HIV-1 RT interaction with cellular eEF1A, likely through changes in the structure of RT. 2018 mBio Result HIV L303A;W252A 48;38 53;43 RT;RT 81;160 83;162 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Our simulations show that the W252A and L303A mutations disrupted the peptide backbone across residues 250 to 253, which have a beta-strand-like conformation, and resulted in increased flexibility in the unstructured loop spanning residues 244 to 249. 2018 mBio Result HIV L303A;W252A 40;30 45;35 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Overall, these data suggest that the W252A and L303A mutations result in changes in the local conformation and intramolecular interactions of the surface-exposed residues of the HIV-1 thumb domain. 2018 mBio Result HIV L303A;W252A 47;37 52;42 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Similar concentrations of the purified WT and E300R mutant RT heterodimer contained similar amounts of active RT measured in a standard in vitro assay with a homopolymer poly(A) DNA template and oligo(dT) primers. 2018 mBio Result HIV E300R 46 51 RT;RT 59;110 61;112 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Since the E300R RT mutation reduced binding to eEF1A the most, it was used to confirm the co-IP and NanoBRET binding results in an in vitro system with the RTp51/p66 heterodimer. 2018 mBio Result HIV E300R 10 15 RT;RT 16;156 18;158 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The assay showed that the E298R mutation caused a significant 60% reduction in RT catalytic activity, the E297R mutation caused a significant 50% increase in RT activity, and the E300R mutation had no significant effect on in vitro RT catalytic activity compared to the WT. 2018 mBio Result HIV E297R;E298R;E300R 106;26;179 111;31;184 RT;RT;RT 79;158;232 81;160;234 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The average uncoating half-life of the E298R mutant (45 min) and the E300R mutant (54 min) was significantly longer than that of the WT and the E297R mutant (37 min). 2018 mBio Result HIV E297R;E298R;E300R 144;39;69 149;44;74 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The biosensor was then incubated in 90 nM WT or E300R mutant RT heterodimer, and these proteins had similar association rate constants. 2018 mBio Result HIV E300R 48 53 RT 61 63 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The combined evidence indicates that the E298R and E300R mutations, which reduce the RT-eEF1A interaction, result in reduced early- and late-stage reverse transcription but have a greater effect on late-stage DNA synthesis. 2018 mBio Result HIV E298R;E300R 41;51 46;56 RT;RT 147;85 168;87 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The combined results suggest that the E298R and E300R mutations of RT reduced the interaction with eEF1A and impaired uncoating and reverse transcription and caused defective virus replication in Jurkat cells, primary CD4+ T cells, and TZM-bl cells. 2018 mBio Result HIV E298R;E300R 38;48 43;53 RT;RT 132;67 153;69 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E297R, E298R, and E300R mutations, which represent weak, medium, and strong impairment of the RT-eEF1A interaction, respectively, were introduced into the HIV-1NL4.3 and HIV-1NL4.3-Deltaenv-eGFP reporter proviral plasmids to produce infectious HIV-1 particles in HEK293T cells. 2018 mBio Result HIV E297R;E298R;E300R 4;11;22 9;16;27 RT 98 100 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E300R mutant RT heterodimer subunits had substantially reduced co-IP with eEF1A compared to the WT RT heterodimer subunits. 2018 mBio Result HIV E300R 4 9 RT;RT 17;103 19;105 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E300R mutant, which has RT catalytic activity similar to that of WT HIV-1 in vitro, produced far less HIV-1 in Jurkat cells. 2018 mBio Result HIV E300R 4 9 RT 28 30 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The ratio of late-stage DNA copies to first strand transfer DNA copies was approximately 20% lower for the E298R and E300R mutants than for the WT and the E297R mutant, indicating that these viruses had reduced efficiency of late-stage DNA synthesis (Table 1). 2018 mBio Result HIV E297R;E298R;E300R 155;107;117 160;112;122 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The results show that the E298R mutant, which had the lowest level of RT catalytic activity in vitro. 2018 mBio Result HIV E298R 26 31 RT 70 72 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The results showed that HIV-1 with the E297R RT mutation replicated similarly to WT HIV-1 in human Jurkat. 2018 mBio Result HIV E297R 39 44 RT 45 47 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The reverse transcription kinetics of the E297R mutant were similar to those of the WT virus. 2018 mBio Result HIV E297R 42 47 RT 4 25 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The time when half of the viral RTCs had completed reverse transcription was approximately 2 h later for HIV-1 with the E300R mutation (50% delay), 4 h later for HIV-1 with the E298R mutation (100% delay), and 30 min later for E297R (14% delay) than for WT HIV-1. 2018 mBio Result HIV E297R;E298R;E300R 227;177;120 232;182;125 RT 51 72 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The virion E300R mutant RT activity compared to that of the WT correlated with results obtained with a purified recombinant RT heterodimer. 2018 mBio Result HIV E300R 11 16 RT;RT 24;124 26;126 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The WT and E300R mutant RT heterodimer subunits were cotransfected in all possible combinations, and an anti-eEF1A antibody was used to immunoprecipitate eEF1A in cell lysates. 2018 mBio Result HIV E300R 11 16 RT 24 26 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. These results suggest that, after taking into account the RT enzymatic activity changes, only the E300R mutation, which had the greatest negative effect on the RT-eEF1A interaction, also significantly affects virus infectivity in HeLa cells. 2018 mBio Result HIV E300R 98 103 RT;RT 58;160 60;162 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. This further indicates that the E300R mutation did not affect RT enzymatic activity, including RNase H activity. 2018 mBio Result HIV E300R 32 37 RT 62 64 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. This is in agreement with the co-IP and NanoBRET finding that the E300R mutation impairs the interaction of RT with eEF1A. 2018 mBio Result HIV E300R 66 71 RT 108 110 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. This led to the E300R mutant RT heterodimer having 3-fold weaker eEF1A binding affinity than the WT. 2018 mBio Result HIV E300R 16 21 RT 29 31 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. This pattern was similar in TZM-bl cells, where the E298R and E300R mutant viruses replicated significantly less than the WT virus (P < 0.05) and E300R mutant HIV-1 had the least replication. 2018 mBio Result HIV E298R;E300R;E300R 52;62;146 57;67;151 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. This showed that there was no statistically significant difference between the WT and E300R mutant HIV-1 strains in the level of ssDNA. 2018 mBio Result HIV E300R 86 91 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Thus, NanoBRET assays support and mirror the co-IP results and indicate that mutation of surface-exposed acidic residues to arginine resulted in impairment of the interaction of HIV-1 RT with eEF1A, with E300R being the most significant example of this. 2018 mBio Result HIV E300R 204 209 RT 184 186 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. To further investigate the activity of RT in the E300R virions, an endogenous reverse transcription (ERT) assay was performed with similar amounts of WT and E300R virions incubated with deoxynucleoside triphosphates (dNTPs). 2018 mBio Result HIV E300R;E300R 49;157 54;162 RT;RT 78;39 99;41 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. We found that the E297R and D250R mutations reduced the interaction with recombinant eEF1A by approximately 20 and 33% compared to WT RT, respectively, although this was not statistically significant. 2018 mBio Result HIV D250R;E297R 28;18 33;23 RT 134 136 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. While HIV-1 with WT, E297R mutant, and E300R mutant RT had at least 90% completion of first strand transfer, HIV-1 with the E298R mutation in RT had reduced first strand transfer efficiency (Table 1), confirming enzymatic defects. 2018 mBio Result HIV E297R;E298R;E300R 21;124;39 26;129;44 RT;RT 52;142 54;144 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. WT HIV-1 infection produced 57% eGFP-positive cells, while E297R, E298R, and E300R mutant infections produced 52, 42, and 23% eGFP-positive cells, respectively (mean of six experiments). 2018 mBio Result HIV E297R;E298R;E300R 59;66;77 64;71;82 HIV infections 3 18 29595649 Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. By using UDPS, 1 (aged 1 year) of 7 children (14.3%) from the case-group harbored viruses with K103N (8.3% prevalence; mutational load: 190,567 copies/mL), a nonpolymorphic mutation causing high-level resistance to NVP and efavirenz (EFV). 2018 Medicine Result HIV K103N 95 100 29595649 Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. In the control-group, UDPS detected V179D at minority-level (2.9%), a polymorphic accessory mutation selected under EFV, in a child aged 6 years (Table 3). 2018 Medicine Result HIV V179D 36 41 29595649 Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. Only E138A (5.9%), an accessory polymorphism weakly selected under etravirine (ETR) and rilpivirine (RPV), was found in a child aged 8 years from the control group. 2018 Medicine Result HIV E138A 5 10 29595649 Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. UDPS revealed a virus harboring 2 major DRMs: L74 V at minority-level (2.5%), causing high- and intermediate-level resistance respectively to didanosine and to ABC; Y181C at population-level (96.7%), causing high- and intermediate-level resistance respectively to NVP and to EFV, ETR, and RPV (Table 3). 2018 Medicine Result HIV L74V;Y181C 46;165 51;170 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Among 34 HIV-infected participants with M184V/I, the median CPE value was 7 (interquartile range [IQR], 7-8), consistent with median CPE values in published studies, while GSS-adjusted CPE values were 6 (IQR 4-7) in plasma and 3.5 (IQR 3-4) in CSF (Figure 3C). 2018 Clinical infectious diseases Result HIV M184I;M184V 40;40 47;47 HIV infections 9 21 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Among participants with CSF escape using the combined dataset of cohort participants and published CSF cases, M184V or M184I (M184V/I) mutations were detected in CSF and plasma in 61% (34/56) and 30% (16/55) of samples, respectively, while M184V/I mutations in CSF and plasma were detected in only 7% (3/43) of samples from participants without escape (Supplementary Table 5). 2018 Clinical infectious diseases Result HIV M184I;M184I;M184I;M184V;M184V;M184V 119;126;240;110;126;240 124;133;247;115;133;247 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Given the high frequency of M184V/I detected in all samples (28%, 56/197), these mutations were combined with thymidine-analog mutations (TAMs; ie, M41L, L210W, T215Y, D67N, K70R, T215F, K219Q/E) for analysis. 2018 Clinical infectious diseases Result HIV D67N;K219E;K219Q;K70R;L210W;M184I;M184V;M41L;T215F;T215Y 168;187;187;174;154;28;28;148;180;161 172;194;194;178;159;35;35;152;185;166 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. In 23% (13/56) of CSF escape cases, M184V/I mutation was detected with at least 1 TAM in CSF compared to 15% (8/55) in plasma, potentially lowering the threshold for accumulation of other mutations that lead to NRTI cross resistance in the CNS (Figure 3D). 2018 Clinical infectious diseases Result HIV M184I;M184V 36;36 43;43 NRTI 211 215 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. In participants with CSF escape and M184V/I mutations, GSS-adjusted CPE values were <5 for CSF and plasma in 27 (79%) and 13 (38%) of 34 participants, respectively, indicating that the majority of those with M184V/I mutations and CSF escape have a low estimated ART penetration in the CNS (Supplementary Table 6). 2018 Clinical infectious diseases Result HIV M184I;M184I;M184V;M184V 36;208;36;208 43;215;43;215 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. M184V/I Mutations and CPE Values. 2018 Clinical infectious diseases Result HIV M184I;M184V 0;0 7;7 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. M184V/I mutations reduce HIV-1 viral fitness, can delay emergence of TAMs, and are frequently present in ART-experienced individuals. 2018 Clinical infectious diseases Result HIV M184I;M184V 0;0 7;7 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. We therefore identified ART-experienced participants with CSF escape and M184V/I mutations on genotypic resistance tests in CSF and/or plasma from published studies (n = 34) and calculated CPE values based on reported ART drug regimens at CSF escape. 2018 Clinical infectious diseases Result HIV M184I;M184V 73;73 80;80 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. All six compounds showed same sensitivity order against the six mutant viruses as follows: Y188L (least sensitive to these compounds) < L100I < F227L + V106A < K103 N < Y181L < E138K (most sensitive to these compounds). 2018 European journal of medicinal chemistry Result HIV E138K;F227L;K103N;L100I;V106A;Y181L;Y188L 177;144;160;136;152;169;91 182;149;166;141;157;174;96 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Among them, compounds 3b2 and 3b8 which contain N atom as hydrogen bond acceptor have the best activity against E138K strain. 2018 European journal of medicinal chemistry Result HIV E138K 112 117 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. And the inhibition assay for a panel of more mutant strains L100I, K103 N, E138K, Y181C, Y188L and F227L + V106A were conducted as well for selected compounds. 2018 European journal of medicinal chemistry Result HIV E138K;F227L;K103N;L100I;V106A;Y181C;Y188L 75;99;67;60;107;82;89 80;104;73;65;112;87;94 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Besides, all six triazole analogues had lower EC50 values than both NVP and DLV against K103 N, Y181C, F227L + V106A, meanwhile they have better potency against Y188L than NVP. 2018 European journal of medicinal chemistry Result HIV F227L;K103N;V106A;Y181C;Y188L 103;88;111;96;161 108;94;116;101;166 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. But since the two compounds and 3b9 had better cytotoxic properties, they showed much higher selectivity (3b2: SI = 2631, 3b8: SI = 4189, 3b9: SI = 6800 against E138K; 3b2: SI = 450, 3b8: SI = 686, 3b9: SI = 761 against Y181C) than ETR (SI = 179 against E138K and SI = 159 against Y181C) when against E138K and Y181C mutant virus strains (Table 4). 2018 European journal of medicinal chemistry Result HIV E138K;E138K;E138K;Y181C;Y181C;Y181C 161;254;301;220;281;311 166;259;306;225;286;316 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Comparison of the mutated RT (E138K, from PDB 2HNZ, cyan) with WT RT (from PDB 3MEC, green) showed that most parts of the two structures superposed on each other with a perturbation in the positions of some of sidechains and only bearing one large change at the mutation site. 2018 European journal of medicinal chemistry Result HIV E138K 30 35 RT;RT 26;66 28;68 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Especially, for 3b8, the most potent compounds against E138K strain, there was two additional hydrogen bonds with K138 and R172, respectively. 2018 European journal of medicinal chemistry Result HIV E138K 55 60 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. For example, these molecules all had single digit micromolar EC50 values against Y188L strain; for K103 N mutated virus, six compounds exhibited EC50 ranging from 0.25 to 1.03 muM; all tested compounds except for 3b7 with amide showed EC50 under 40 nM against E138K strain which is better than the control drug NVP and DLV and comparable to ETR and AZT. 2018 European journal of medicinal chemistry Result HIV E138K;K103N;Y188L 260;99;81 265;105;86 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Regarding the resistance fold (RF, ratio of EC50 against mutant strain/EC50 against WT strain), compounds 3b2, 3b3, 3b7, 3b8 showed the values for E138K less than 1 while ETR had the RF of 3.5 (Table 3). 2018 European journal of medicinal chemistry Result HIV E138K 147 152 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Since there was no available crystal complex of E138K RT with ETR, we obtained the RT harboring E138K from the crystal complex with PETT-2 (PDB: 2HNZ). 2018 European journal of medicinal chemistry Result HIV E138K;E138K 48;96 53;101 RT;RT 54;83 56;85 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. That means these compounds inhibited the E138K mutant strain specifically with a better EC50 than against the WT virus. 2018 European journal of medicinal chemistry Result HIV E138K 41 46 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. The extracted ligand PETT-2 (gray) overlapped well with the upper part of ETR (pink) which was docked into the E138K mutant RT (cyan): two pyridine rings just occupied the position where the two phenyl wings of ETR were; the thiourea also could form a hydrogen bond with carboxyl of K101. 2018 European journal of medicinal chemistry Result HIV E138K 111 116 RT 124 126 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. The newly synthesized diarylnicotinamide triazole derivatives were evaluated for their activities against WT HIV-1 strain (IIIB), most common K103 N + Y181C double mutant HIV-1 strain (RES056) and HIV-2 strain (ROD) in MT-4 cells using the MTT method. 2018 European journal of medicinal chemistry Result HIV K103N;Y181C 142;151 148;156 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. These findings implicated a same inhibitory mechanism of these analogues, especially verified the introduction of a longer triazole tail may help to bind tighter to the RT containing E138K. 2018 European journal of medicinal chemistry Result HIV E138K 183 188 RT 169 171 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. These findings may explain the reason that this series had good potency against the key drug resistant mutant to the new generation HIV-1 NNRTIs E138K and confirmed our rational design as effective strategy to overcome the drug-resistant issues. 2018 European journal of medicinal chemistry Result HIV E138K 145 150 NNRTI 138 144 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. They showed better potencies than the first generation NNRTIs NVP and DLV against most of the mutants and were equally potent with ETR and AZT against E138K strain. 2018 European journal of medicinal chemistry Result HIV E138K 151 156 NNRTI 55 61 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. To better explain the SAR and find the potential binding modes of this series of molecules, the two representative compounds 3b8 and 3b9 were docked into the NNRTIs binding pocket in WT and E138K mutated RT using the Surflex-Dock of SYBYL-X 2.0. 2018 European journal of medicinal chemistry Result HIV E138K 190 195 NNRTI;RT 158;204 164;206 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. 8B, we observed an overlap between the van der Waals spheres of the PR1V32I+L76M V32_B residue and the PR1L76M M76_B residue. 2018 Scientific reports Result HIV L76M 76 80 PR;PR 68;103 71;106 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Figure 8B shows the conformation of residues 45_B, 76_B and 32_B in the five PR1V32I+L76M mutants. 2018 Scientific reports Result HIV L76M 85 89 PR 77 80 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Five of these mutations (Q7K, L33I, L63I, C67A, and C95A) correspond to classical experimental mutations introduced to minimize autoproteolysis and to prevent cysteine-thiol oxidation of PR1. 2018 Scientific reports Result HIV C67A;C95A;L33I;L63I;Q7K 42;52;30;36;25 46;56;34;40;28 PR 187 190 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. For example, the substitution of the threonine at position 32 by a serine resulted in atom CD1 (PDB atom name) of residue 32 of both chains, denoted as 32_A/B_CD1, were observed in only PR2 pockets. 2018 Scientific reports Result HIV T32S 37 73 PR 186 189 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. In addition, the classification of mutant and wild-type PR1 and PR2 structures showed that 14% of PR1 mutant structures with the mutation I32V are clustered with wild-type PR2 structure in sub-cluster 3. 2018 Scientific reports Result HIV I32V 138 142 PR;PR;PR;PR 64;172;56;98 67;175;59;101 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. In addition, we noted an overlap between the van der Waals spheres of the PR1V32I+L76M M76_B residue and the PR1 K45_B residue. 2018 Scientific reports Result HIV V32I;L76M 77;82 81;86 PR;PR 74;109 77;112 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. In this section, we studied the link between structural changes observed at residue 45_B between PR1 and PR2 structures and the six substitutions occurring between PR1 and PR2 pockets (T31S, V32I, M46I, I47V, L76M, and V82I). 2018 Scientific reports Result HIV I47V;L76M;M46I;T31S;V32I;V82I 203;209;197;185;191;219 207;213;201;189;195;223 PR;PR;PR;PR 105;172;97;164 108;175;100;167 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Indeed, among the 160 mutant structures with the mutation L76M, 96% were grouped in cluster 2 and only seven mutant belong to cluster 1. 2018 Scientific reports Result HIV L76M 58 62 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. It contains 23% of the PR1 mutant structures with the mutation L76M. 2018 Scientific reports Result HIV L76M 63 67 PR 23 26 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Most of these structures with the mutation I32V (78%) also contain the mutation L76M. 2018 Scientific reports Result HIV I32V;L76M 43;80 47;84 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Of these 48 pocket residues, six were substituted between PR1 and PR2 pockets: T31S, V32I, M46I, I47V, L76M, and V82I. 2018 Scientific reports Result HIV I47V;L76M;M46I;T31S;V32I;V82I 97;103;91;79;85;113 101;107;95;83;89;117 PR;PR 66;58 69;61 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. One mutation (K57L) was observed among the 13 PR2 sequences. 2018 Scientific reports Result HIV K57L 14 18 PR 46 49 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. PR pockets exhibited six amino acid changes (T31S, V32I, M46I, I47V, L76M and V82I). 2018 Scientific reports Result HIV I47V;L76M;M46I;T31S;V32I;V82I 63;69;57;45;51;78 67;73;61;49;55;82 PR 0 2 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. These results suggest that the mutation L76M is important to the structural change of residue 45_B observed between PR1 and PR2 structures. 2018 Scientific reports Result HIV L76M 40 44 PR;PR 124;116 127;119 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. This suggests that the substitution L76M could be responsible for the structural change occurring at position 45_B but is not sufficient to explain all structural differences between PR1 and PR2 pocket. 2018 Scientific reports Result HIV L76M 36 40 PR;PR 191;183 194;186 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Thus, we speculated that substitution V32I in chain B induces a structural change in the M76_B side chain to avoid a steric clash between residues I32_B and M76_B in PR1 mutants. 2018 Scientific reports Result HIV V32I 38 42 PR 166 169 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Thus, we speculated that this second substitution (I32V) plays a role in the residue 45_B deformation by modifying the 76_B side-chain conformation. 2018 Scientific reports Result HIV I32V 51 55 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. To study in more detail the role of mutation L76M in the structural deformation of residues 45_B, we analysed the five single mutant structures containing the mutation L76M, referred to as PR1L76M and numbered from one to five. 2018 Scientific reports Result HIV L76M;L76M 45;168 49;172 PR 189 192 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. To test this second hypothesis, we analysed the five PR1 mutants containing the mutations V32I and L76M, referred to as PR1V32I+L76M and numbered from one to five. 2018 Scientific reports Result HIV L76M;L76M;V32I 99;128;90 103;132;94 PR;PR 53;120 56;123 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. We noted that two single mutant structures with the mutation L76M, noted PR1L76M, belong to this sub-cluster. 2018 Scientific reports Result HIV L76M 61 65 PR 73 76 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. We observed that residues 45_B and 76_B had similar conformations in PR1V32I+L76M mutants and in wild-type PR2. 2018 Scientific reports Result HIV L76M 77 81 PR;PR 107;69 110;72 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. We observed that three mutations (V32I, M46I, and L76M) did not equitably sample clusters 1 and 2, particularly mutation L76M. 2018 Scientific reports Result HIV L76M;L76M;M46I;V32I 50;121;40;34 54;125;44;38 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. We speculate that the composition changes between PR1 and PR2 pockets in main-chain atoms of substituted residues (e.g., 31, 46, and 82) are directly induced by T31S, M46I, and V82I amino acid changes. 2018 Scientific reports Result HIV M46I;T31S;V82I 167;161;177 171;165;181 PR;PR 58;50 61;53 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. 3H) cores made of the hyper-stable E45A CA mutant accumulated in the cytoplasm to a greater extent than WT/CA cores, whereas there were rare surviving IN complexes after the quick uncoating of the unstable K203A CA mutant. 2018 Cell host & microbe Result HIV E45A;K203A 35;206 39;211 IN;Capsid;Capsid;Capsid 151;40;107;212 153;42;109;214 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Also similar to WT viruses, N74D cores co-labeled with INsfGFP and CypA-DsRed docked at the NE and lost the CA marker (n=45. 2018 Cell host & microbe Result HIV N74D 28 32 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Also, disappearance of post-uncoating N74D IN complexes at the NE showed a high degree of correlation with productive integration that was virtually identical to correlation observed for disappearing intra-nuclear WT IN complexes (compare Figs. 2018 Cell host & microbe Result HIV N74D 38 42 IN;IN 43;217 45;219 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Analysis of single N74D core docking and uncoating revealed that, interestingly, the loss of CypA-DsRed from after docking was significantly (>3-fold) slower than for WT cores. 2018 Cell host & microbe Result HIV N74D 19 23 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. However, after uncoating at the NE, N74D IN complexes typically remained colocalized with lamin. 2018 Cell host & microbe Result HIV N74D 36 40 IN 41 43 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. In contrast, post-uncoating N74D complexes remained very close to the NE, even when imaged by super-resolution microscopy. 2018 Cell host & microbe Result HIV N74D 28 32 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. In spite of its marked accumulation around the NE, nuclear entry of the E45A mutant was dramatically reduced compared to WT cores. 2018 Cell host & microbe Result HIV E45A 72 76 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. In spite of poor apparent nuclear penetration, a fraction of N74D uncoating events culminated in disappearance of the INsfGFP signal at the NE followed by eGFP expression. 2018 Cell host & microbe Result HIV N74D 61 65 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Moreover, disappearance of post-uncoating N74D IN complexes at the NE resulted in eGFP expression with a probability similar to the intra-nuclear WT IN complexes (compare Figs. 2018 Cell host & microbe Result HIV N74D 42 46 IN;IN 47;149 49;151 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. The N74D mutation did not affect HIV-1 infectivity. 2018 Cell host & microbe Result HIV N74D 4 8 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. The rarity of docking or nuclear import of post-uncoating INsfGFP complexes, which was abrogated by the destabilizing K203A mutation. 2018 Cell host & microbe Result HIV K203A 118 123 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Together, these results imply that uncoating of N74D cores at the nuclear membrane leads to nuclear import and productive integration in TZM-bl cells. 2018 Cell host & microbe Result HIV N74D 48 52 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. We next ask if the N74D CA mutant, which utilizes an alternative, CPSF6- and NUP153-independent nuclear entry pathway, uncoats at the nuclear pore. 2018 Cell host & microbe Result HIV N74D 19 23 Capsid 24 26 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. A total of 180 patients with at least one observation of the Q151M mutation were recorded in the UK-HDRD, out of a total of 80,281 patients with at least one resistance test. 2018 AIDS research and therapy Result HIV Q151M 61 66 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. At first observation of the Q151M mutation, 18 (10%) patients were recorded as being ART-naive, 139 (77%) as experienced and 23 (13%) as 'not classified'. 2018 AIDS research and therapy Result HIV Q151M 28 33 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Data regarding accessory mutations to Q151M were available in 155 (86%) patients: A62V was present in 49 (32%), V75I in 62 (40%), F77L in 47 (30%) and F116Y in 99 (64%), and 75% of patients showed at least one accessory mutation. 2018 AIDS research and therapy Result HIV A62V;F116Y;F77L;Q151M;V75I 82;151;130;38;112 86;156;134;43;116 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Figure 1a shows the prevalence of the Q151M mutation by calendar year according to whether the patient was ART experienced or naive at the time of blood sample. 2018 AIDS research and therapy Result HIV Q151M 38 43 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. For a total of 62 patients there were data on change to ART regimen after detection of the Q151M mutation and before viral re-suppression (for patients in whom this occurred), but six of these patients were missing a baseline CD4 cell count (three were also missing baseline VL) and so were dropped from the Cox analysis. 2018 AIDS research and therapy Result HIV Q151M 91 96 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. For the matched cohort analysis of mortality, 72 patients with and 665 patients without the Q151M mutation were included. 2018 AIDS research and therapy Result HIV Q151M 92 97 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. In 62/96 (65%) patients, a confirmed undetectable VL was observed (at any point) following the detection of the Q151M mutation at a median of 1.0 (IQR 0.5-2.3) years from the date of the resistance test sample. 2018 AIDS research and therapy Result HIV Q151M 112 117 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. In patients with Q151M, most deaths occurred amongst those with CD4 count < 100 cells/microL (12 deaths/24 patients vs 6/54 for patients with CD4 >= 100 cells/microL, further details in Additional file 1). 2018 AIDS research and therapy Result HIV Q151M 17 22 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Of the patients in whom the Q151M mutation was detected, 96 could be linked to clinical data. 2018 AIDS research and therapy Result HIV Q151M 28 33 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Only 3% of patients showed no other mutation, and the most common associated major reverse transcriptase mutations were M184V (47%), K103N (35%) and K65R (29%). 2018 AIDS research and therapy Result HIV K103N;K65R;M184V 133;149;120 138;153;125 RT 83 104 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Q151M. 2018 AIDS research and therapy Result HIV Q151M 0 5 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Similar to Q151M, the prevalence of the mutation was consistently very low in ART-naive patients, with a maximum of 0.15% (2/1311) in 2003, whilst in ART-experienced patients there was a large fall in prevalence from 0.8% (16/1966) in 2002 to 0.1% (4/3376) in 2006 and then to 0.03% (1/3734) in 2014. 2018 AIDS research and therapy Result HIV Q151M 11 16 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Table 1 provides a summary of the associated major reverse transcriptase mutations at first observation of the Q151M mutation in each of the affected patients. 2018 AIDS research and therapy Result HIV Q151M 111 116 RT 51 72 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. There was no evidence that presence of the Q151M mutation was associated with increased mortality (HR 1.25, 95% CrI 0.84-2.1). 2018 AIDS research and therapy Result HIV Q151M 43 48 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. There was no strong evidence that linked TAMs were associated with the probability of viral suppression, although negative effects cannot be ruled out, and there were no cases with a K65R mutation included in this analysis. 2018 AIDS research and therapy Result HIV K65R 183 187 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Thymidine analogue mutations (TAMs) were most frequently seen, with TAM1 mutations (M41L, L210W and T215Y) being most common. 2018 AIDS research and therapy Result HIV L210W;M41L;T215Y 90;84;100 95;88;105 29683855 A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. An M184V/I mutation associated with phenotypic resistance to emtricitabine and lamivudine was identified in one patient receiving D/C/F/TAF. 2018 AIDS (London, England) Result HIV M184I;M184V 3;3 10;10 29683855 A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. This patient harbored a K103N mutation at screening, indicating transmitted NNRTI (efavirenz and nevirapine) resistance. 2018 AIDS (London, England) Result HIV K103N 24 29 NNRTI 76 81 29684083 HIV-1 transmission networks across Cyprus (2010-2012). Specifically, there was one patient (CY369) infected with an HIV-1 strain with a non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation (K103N) and two patients (CY274 and CY314) with a protease inhibitor (PI) resistance mutation (M46L). 2018 PloS one Result HIV K103N;M46L 157;251 162;255 NNRTI;PR;NNRTI;PI 81;206;129;226 117;214;134;228 29684083 HIV-1 transmission networks across Cyprus (2010-2012). Study subject CY289, a Romanian citizen living in Cyprus, was infected with a sub-subtype F1 dual-class RT resistant strain carrying both K219Q and K103N mutations. 2018 PloS one Result HIV K103N;K219Q 148;138 153;143 RT 104 106 29684083 HIV-1 transmission networks across Cyprus (2010-2012). The second study subject, also a Romanian citizen living in Cyprus, was also infected with a sub-subtype F1strain dual-class RT and PI resistant strain carrying D67N, K70R, M184V, T215F, Y181C, M46L, I54V and V82F mutations associated with drug resistance. 2018 PloS one Result HIV D67N;I54V;K70R;M184V;M46L;T215F;V82F;Y181C 161;200;167;173;194;180;209;187 165;204;171;178;198;185;213;192 PI;RT 132;125 134;127 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. A Slovenian cluster was identified that contributed to the spread of HIV in Serbia, and one person carrying Y181C, which originated from Serbia, was within a Serbian part of the identified cluster; however, none of the Serbian sequences showed the same mutational profile. 2018 PloS one Result HIV Y181C 108 113 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. SDRMs were only found in four individuals (2.4%); namely, mutation K103N in two patients and T68D and T215D in one each. 2018 PloS one Result HIV K103N;T215D;T68D 67;102;93 72;107;97 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. Specifically, the first Slovenian sequence, with the T215D mutation, was found most closely related to a set of sequences carrying T215C obtained from a US citizen. 2018 PloS one Result HIV T215C;T215D 131;53 136;58 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. The first sequence is part of the largest Slovenian cluster (n = 53) and carries the T69D mutation, the second sequence is within a cluster of 20 Slovenian sequences and carries M46I, and the third is in a phylogenetic relationship with two other Slovenian sequences and is carries K103N (Fig 2). 2018 PloS one Result HIV K103N;M46I;T69D 282;178;85 287;182;89 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. The second Slovenian sequence, with T215V, was nested within six sequences from the UK and Poland, all with identified T215 revertants (T215V, T215E or T215D). 2018 PloS one Result HIV T215D;T215E;T215V;T215V 152;143;36;136 157;148;41;141 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. The third sequence, with T215S, was identified in a phylogenetic relationship with two closely related sequences from Germany, and both had the same T215S revertant mutation. 2018 PloS one Result HIV T215S;T215S 25;149 30;154 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. This cluster included the Slovenian sequence with T215V nested within foreign sequences with 215 revertants; however, the phylogenetic link remained regardless of the exclusion of SDRM sites. 2018 PloS one Result HIV T215V 50 55 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. Analysis of the three most prevalent NNRTI mutations is shown in Figure 6; the prevalence of the K103N/S mutation continued to increase until 2008 (6% in 2008) and then declined in prevalence in 2009 to 3%. 2018 AIDS research and human retroviruses Result HIV K103N;K103S 97;97 104;104 NNRTI 37 42 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. The most prevalent NNRTI mutation was K103N/S with 4%, 95% CI: 3.7%-5.0%. 2018 AIDS research and human retroviruses Result HIV K103N;K103S 38;38 45;45 NNRTI 19 24 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. The most prevalent NRTI mutation was M41L with 1.5%, 95% CI: 1.1%-1.8%. 2018 AIDS research and human retroviruses Result HIV M41L 37 41 NRTI 19 23 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. The prevalence of major PI mutations was 3% [95% CI (2.6%-3.8%)], and the most prevalent PI mutation was L90M [1%, 95% CI (0.7%-1.4%)]. 2018 AIDS research and human retroviruses Result HIV L90M 105 109 PI;PI 24;89 26;91 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. The prevalence of major PI mutations was 3%, 95% CI: 2.8%-4.0%, while the most prevalent PI mutation was L90M [1%, 95% CI (0.8%-1.5%)]. 2018 AIDS research and human retroviruses Result HIV L90M 105 109 PI;PI 24;89 26;91 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. The prevalence of NNRTI mutations was 6% [95% CI (5.5%-7.0%)], and the most prevalent NNRTI mutation was K103N/S [4%, 95% CI (3.7%-5.0%)]. 2018 AIDS research and human retroviruses Result HIV K103N;K103S 105;105 112;112 NNRTI;NNRTI 18;86 23;91 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. For NNRTI resistance-associated mutations, V179D/T was identified as the major mutation (20 cases), and the other 6 types of mutation were E138A, A98G, K101P, K103 N, Y181H and Y188H. 2018 BMC infectious diseases Result HIV A98G;E138A;K101P;K103N;V179D;V179T;Y181H;Y188H 146;139;152;159;43;43;167;177 150;144;157;165;50;50;172;182 NNRTI 4 9 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. In addition, there was only one PI resistance-associated mutation found (L33F) in 5 cases. 2018 BMC infectious diseases Result HIV L33F 73 77 PI 32 34 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. NRTI resistance-associated mutations found in this population included M184 V (n = 3, 6.67%), M41 L (n = 2, 4.44%), T215F (n = 2, 4.44%), L74F/V (n = 2, 4.44%), D67G (n = 1, 2.22%) and K70Q (n = 1, 2.22%) (Figure1). 2018 BMC infectious diseases Result HIV D67G;K70Q;L74F;L74V;M184V;M41L;T215F 161;185;138;138;71;94;116 165;189;144;144;77;99;121 NRTI 0 4 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. Excluding FD83 and GL26, of which the early plasmas did not neutralize GB40_w2_1, both FF69 and DD80 wave 1 plasmas neutralized GB40_w2_1, but the neutralization sensitivities were not reduced upon the N462S mutation (Figure 4c, middle). 2018 Viruses Result HIV N462S 202 207 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. Note that N462 is a putative N-linked glycosylation site, and the N462S mutation has been associated with the N462 glycan shifting to N461 in the resistant clones. 2018 Viruses Result HIV N462S 66 71 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. The N462S mutation rendered the sensitive GB40_w2_1 clone resistant to GB40 wave 1 neutralization, as assessed by the GB40_19wpi plasma (Figure 4c, left), indicating that GB40 wave 1 targeted the N462 glycan. 2018 Viruses Result HIV N462S 4 9 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. To map the targets of wave 1 neutralizing antibodies, we aligned the amino acid sequences of the tested Env clones and identified two mutations in gp120 V5 that were associated with changes in neutralization sensitivity, N462S for GB40_w2_1 and G460aE for FF69_w2 and FF69_w8 clones (Figure 4a). 2018 Viruses Result HIV N462S 221 226 gp120;Env 147;104 152;107 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. Two macaques without breadth, EN13 and FF94, also neutralized GB40_w2_1 (Figure 4c, right); the EN13_29wpi plasma was moderately sensitive to N462S, and the FF94_29wpi plasma was not sensitive. 2018 Viruses Result HIV N462S 142 147 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. 8d, e), but Tat S16D and Tat S46D mutants showed the strongest reduction in cyclin T1 binding. 2018 Retrovirology Result HIV S16D;S46D 16;29 20;33 Tat;Tat 12;25 15;28 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Although, Calpha Root-Mean-Square Deviation (RMSD) of this segment at 20 ns MD time in comparison with the initial conformation is almost identical for S16&S46 and S16P&S46P complexes (0.7A and 0.8A respectively), the positions of the Zn2+ ions were shifted from their initial crystal structure positions by more than 4 A indicating rigid body-like rotation of the Tat segment due to relocation of phosphorylated Ser-16 side chains from the internal to the external position. 2018 Retrovirology Result HIV S16P;S46P 164;169 168;173 Tat 365 368 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Both Tat S16A and Tat S16D mutants remained monoubiquitinated. 2018 Retrovirology Result HIV S16A;S16D 9;22 13;26 Tat;Tat 5;18 8;21 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Both Tat S16A and Tat S46A mutations strongly reduced luciferase expression to 2 and 0.1% respectively, suggesting inhibition of HIV-1 transcription. 2018 Retrovirology Result HIV S16A;S46A 9;22 13;26 Tat;Tat 5;18 8;21 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Both Tat S16D and Tat S46A mutants bound to TAR RNA. 2018 Retrovirology Result HIV S16D;S46A 9;22 13;26 Tat;Tat 5;18 8;21 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. During 20 ns MD the second flexible domain (residues 18-25 & 29-37) of Tat in S16P&S46P complex rotated as a rigid body by 33.2 as compared to the position of the domain in S16&S46 CCT complex. 2018 Retrovirology Result HIV S16P;S46P 78;83 82;87 Tat 71 74 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Figure 9a shows spatial superposition of the S16&S46 and the S16P&S46P complexes at the final point of the 20 ns MD trajectory. 2018 Retrovirology Result HIV S16P;S46P 61;66 65;70 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. However, Tat S46E showed more diffused localization similar to EGFP suggesting that it may have a defect. 2018 Retrovirology Result HIV S46E 13 17 Tat 9 12 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. In contrast, Tat S46E mutation only demonstrated minimal 4% transcription efficiency comparing to WT Tat. 2018 Retrovirology Result HIV S46E 17 21 Tat;Tat 13;101 16;104 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. In contrast, the virus with Tat S46E did not replicate well (11% comparing to WT. 2018 Retrovirology Result HIV S46E 32 36 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. None of the Tat mutations, except Tat S46D and previously reported Tat K71A mutant, showed reduced ubiquitination. 2018 Retrovirology Result HIV K71A;S46D 71;38 75;42 Tat;Tat;Tat 12;34;67 15;37;70 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Tat S16A mutant had a reduced binding to TAR RNA (40% reduction. 2018 Retrovirology Result HIV S16A 4 8 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Tat S16A mutation reduced Tat binding to TAR RNA. 2018 Retrovirology Result HIV S16A 4 8 Tat;Tat 0;26 3;29 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Tat S16D and Tat S46D mutations reduced Tat binding to CDK9/cyclin T1. 2018 Retrovirology Result HIV S16D;S46D 4;17 8;21 Tat;Tat;Tat 0;13;40 3;16;43 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Tat S16E mutation showed minimal effect (52%. 2018 Retrovirology Result HIV S16E 4 8 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Tat S46D mutant showed some reduction in TAR RNA binding but it was not statistically significant. 2018 Retrovirology Result HIV S46D 4 8 Tat 0 3 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Tat Ser-16 alanine mutation inhibits HIV-1 transcription and Tat S16E mutation restores it. 2018 Retrovirology Result HIV S16A;S16E 4;65 18;69 Tat;Tat 0;61 3;64 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. The virus with Tat S16E mutation replicated well (61% comparing to WT Tat. 2018 Retrovirology Result HIV S16E 19 23 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Thus we normalized p24 levels for Tat S16E and Tat S46E viruses but not for Tat S16A and Tat S46S viruses that produced background levels of p24. 2018 Retrovirology Result HIV S16A;S16E;S46E;S46S 80;38;51;93 84;42;55;97 p24;p24;Tat;Tat;Tat;Tat 19;141;34;47;76;89 22;144;37;50;79;92 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Thus, viruses assembled from proviral vectors with Tat S16E or Tat 46E mutations led to generation of replication capable viruses. 2018 Retrovirology Result HIV S16E 55 59 Tat;Tat 51;63 54;66 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. To analyze the effect of Tat phosphorylation on the binding to CDK9/cyclin T1, we expressed Flag-tagged Tat and Tat S16A, S16D, S46A and S46D mutants along with cyclin T1 and then immunoprecipitated Tat with anti-Flag antibodies. 2018 Retrovirology Result HIV S16A;S16D;S46A;S46D 116;122;128;137 120;126;132;141 Tat;Tat;Tat;Tat 25;104;112;199 28;107;115;202 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. To confirm phosphorylation of Tat in vivo, Flag-tagged WT Tat, Tat S16A and Tat S46A mutants were expressed in 293T cells. 2018 Retrovirology Result HIV S16A;S46A 67;80 71;84 Tat;Tat;Tat;Tat 30;58;63;76 33;61;66;79 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. To elucidate structural consequences of Tat phosphorylation at Ser-16 and Ser-46, we performed 20 ns Molecular Dynamics (MD) simulations in a periodical water box for the CDK9/Cyclin T1/Tat protein complexes in which Tat was non-phosphorylated on Ser-16 and Ser-46 (S16&S46) or double phosphorylated (S16P&S46P). 2018 Retrovirology Result HIV S16P;S46P 301;306 306;310 Tat;Tat;Tat 40;186;217 43;189;220 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. We could only assemble viruses with Tat S16E or Tat S46E mutations and not with Tat S16A or Tat S46A mutations. 2018 Retrovirology Result HIV S16A;S16E;S46A;S46E 84;40;96;52 88;44;100;56 Tat;Tat;Tat;Tat 36;48;80;92 39;51;83;95 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. WT Tat and all mutants except Tat S46E were localized in the nucleus. 2018 Retrovirology Result HIV S46E 34 38 Tat;Tat 3;30 6;33 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. Global sequence analysis showed that the most frequent amino acid substitutions in RT were S162C (29.4%), T200A (35.3%), M184V (32.3%), L214F (67.6%), I135T (55.9%), D177E (26.5%) and E122K (44.1%), and the most in PR were V15I (41.2%), M36I (38.2%) and E35D (23.5%). 2018 Scientific reports Result HIV E35D;L214F;M184V;M36I;S162C 254;136;121;237;91 258;141;126;241;96 PR;RT 215;83 217;85 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. On the other hand, the minor mutations to PI found were S37N (32.3%), I15V (26.5%) and M36I (23.5%). 2018 Scientific reports Result HIV M36I 87 91 PI 42 44 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. Only one (11.1%) patient showed the TAM 1 (M41L, L210W and T215Y) mutation pathway, and one patient (11.1%) had both pathways. 2018 Scientific reports Result HIV L210W;M41L 49;43 54;47 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The first iterative pruning (S_3TC exclusion) showed that susceptibility to Emtricitabine (S_FTC) is another important attribute, and its exclusion revealed that susceptibility to Nelfinavir (S_NFV), T215F_NRTI, F225H_NNRTI, A71_minorIP and S_NVP are also important attributes. 2018 Scientific reports Result HIV F225H 212 217 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The major mutations to PI were I54V (2.9%), V82A (11.7%), M46I (8.8%) and L90M (40.4%). 2018 Scientific reports Result HIV L90M;M46I 74;58 78;62 PI 23 25 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The TAM mutation way more present was TAM 2 (D67N, K70R, T215F and K219Q/E), and was present in seven (77.8%) patients. 2018 Scientific reports Result HIV K70R 51 55 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. Thymidine Analog Mutations (TAMs) were found in nine (26.5%) samples, with one or more mutations among M41L, D67N, K70R, L210W, T215Y/F e K219Q/E. 2018 Scientific reports Result HIV K70R;L210W;M41L 115;121;103 119;126;107 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. A62V, a non-SDRM TDF-associated accessory DRM, occurred in 10 individuals. 2019 Clinical infectious diseases Result HIV A62V 0 4 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. Figure 5 contains a time-scaled Bayesian phylogenetic tree that illustrates in red the likely origin of the cluster of 12 viruses containing the NNRTI DRM Y181C plus the PI DRM L90M. 2019 Clinical infectious diseases Result HIV L90M;Y181C;L90M;Y181C 178;156;177;155 182;161;181;160 NNRTI;PI 145;170 150;172 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. However, the primary TAMs T215F/Y were present in just 5 individuals. 2019 Clinical infectious diseases Result HIV T215F;T215Y 26;26 33;33 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. K70N/T/S, which are not on the SDRM but are associated with low-level TDF resistance, occurred in 3 individuals including 1 without an SDRM. 2019 Clinical infectious diseases Result HIV K70N;K70S;K70T 0;0;0 8;8;8 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. M184V/I occurred in 20 individuals, comprising 7.3% of NRTI SDRMs. 2019 Clinical infectious diseases Result HIV M184I;M184V 0;0 7;7 NRTI 55 59 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. Of the 203 PI-associated SDRMs, the most common were L90M (33.5%), M46I/L (19.7%), I54V (10.8%), V82A/L/T (10.4%), and D30N plus N88D (9.8%). 2019 Clinical infectious diseases Result HIV D30N;I54V;L90M;M46I;M46L;N88D;V82A;V82L;V82T 119;83;53;67;67;129;97;97;97 123;87;57;73;73;133;105;105;105 PI 11 13 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The mutations E138A/G/K/Q, which are associated with reduced RPV susceptibility but are not on the SDRM list, occurred in 99 individuals, including 90 without an SDRM. 2019 Clinical infectious diseases Result HIV E138A;E138G;E138K;E138Q 14;14;14;14 25;25;25;25 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The mutations K103N/S, Y181C, Y188L, and G190A accounted for 88.5% of the 348 NNRTI SDRMs. 2019 Clinical infectious diseases Result HIV G190A;K103N;K103S;Y181C;Y188L 41;14;14;23;30 46;21;21;28;35 NNRTI 78 83 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The next most common SDRMs, V32I, I50V/L, L76V, and I84V, each occurred in <=5 individuals. 2019 Clinical infectious diseases Result HIV I50L;I50V;I84V;L76V;V32I 34;34;52;42;28 40;40;56;46;32 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The non-TAMs K65R, L74V/I, Y115F, and Q151M each occurred in just 1 or 2 individuals. 2019 Clinical infectious diseases Result HIV K65R;L74I;L74V;Q151M;Y115F 13;19;19;38;27 17;25;25;43;32 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The polymorphic mutation E138A accounted for 87 of these 99 mutations. 2019 Clinical infectious diseases Result HIV E138A 25 30 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The TDF-associated SDRM K70E did not occur. 2019 Clinical infectious diseases Result HIV K70E 24 28 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. As K65R, Y181C/I, and K103N were the most common RAMs in our patients receiving nNRTI-containing regimens with virological failure, univariate and multivariate logistic regression analyses were performed to identify the factors associated with these emergent RAMs. 2018 Infection and drug resistance Result HIV K103N;K65R;Y181C;Y181I 22;3;9;9 27;7;16;16 NNRTI 80 85 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. For the patients experiencing virological failure with emergent K65R, regimens containing TDF/FTC or TDF plus lamivudine and nevirapine were more likely to be associated with emergence of K65R compared with other regimens (adjusted odds ratio [AOR] 6.02; 95% CI 1.36-27.03) (Table 2A). 2018 Infection and drug resistance Result HIV K65R;K65R 64;188 68;192 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. In multivariate analysis, use of regimens of TDF/FTC or TDF plus lamivudine and nevirapine was statistically significantly associated with emergence of Y181C/I (AOR 31.25; 95% CI 6.21-166.67) (Table 2B). 2018 Infection and drug resistance Result HIV Y181C;Y181I 152;152 159;159 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. Of the 26 patients who received 2 NRTIs plus efavirenz, only 1 patient (3.8%) had resistance to K65R and nNRTIs (Figure 3). 2018 Infection and drug resistance Result HIV K65R 96 100 NNRTI;NRTI 105;34 111;39 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. Of the 43 patients who received 2 NRTIs plus nevirapine, 19 (44.2%) had resistance to K65R and nNRTI with or without M184V/I. 2018 Infection and drug resistance Result HIV K65R;M184I;M184V 86;117;117 90;124;124 NNRTI;NRTI 95;34 100;39 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. Of the emergent RAMs to NRTIs, M184V/I (42.3%) and K65R (28.2%) were the most common; and of those RAMs to nNRTIs, Y181C (42.3%) and K103N (15.5%) were the most common, followed by G190A/E/Q (12.7%) and V179D/E (12.7%), and V108I (9.9%) (Figure 2). 2018 Infection and drug resistance Result HIV G190A;G190E;G190Q;K103N;K65R;M184I;M184V;V108I;V179D;V179E;Y181C 181;181;181;133;51;31;31;224;203;203;115 190;190;190;138;55;38;38;229;210;210;120 NNRTI;NRTI 107;24 113;29 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. The emergence of M184V/I mutations was less common than RAMs to nNRTI in patients with virological failure who received 2 NRTIs plus nevirapine (51.2% vs 83.7%) as well as in those who received 2 NRTIs plus efavirenz (26.9% vs 61.5%) (Figure 3). 2018 Infection and drug resistance Result HIV M184I;M184V 17;17 24;24 NNRTI;NRTI;NRTI 64;122;196 69;127;201 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. The use of zidovudine/lamivudine plus efavirenz (AOR 38.46; 95% CI 2.11-1000) was statistically significantly associated with the presence of K103N mutation (Table 2C). 2018 Infection and drug resistance Result HIV K103N 142 147 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Among the minority NNRTI mutations, V108I, V179T were detected in four samples and G190A, H221Y and K101E were detected in three samples. 2018 African journal of laboratory medicine Result HIV G190A;H221Y;K101E;V108I;V179T 83;90;100;36;43 88;95;105;41;48 NNRTI 19 24 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Among the minority NRTI mutations, M184I was detected in three samples, and M184V and K65R in two samples respectively. 2018 African journal of laboratory medicine Result HIV K65R;M184I;M184V 86;35;76 90;40;81 NRTI 19 23 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. From the 1% mixed clone, K103N was not detected within the 520 sequence reads; Y181C and M184V were detected at the level of 1.03% with 1335 reads, while G190A was detected at 0.97% with 785 reads. 2018 African journal of laboratory medicine Result HIV G190A;K103N;M184V;Y181C 154;25;89;79 159;30;94;84 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Other minority mutations including M41L, A62V, D67N, T69D, V75M, T215F and K219E were found in one sample each. 2018 African journal of laboratory medicine Result HIV A62V;D67N;K219E;M41L;T215F;T69D;V75M 41;47;75;35;65;53;59 45;51;80;39;70;57;63 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Other NNRTI mutations, such as V90I, K103N, V106A/M, E138A, V179E, Y181C, Y188C/L and G190E were also found in one or two samples. 2018 African journal of laboratory medicine Result HIV E138A;G190E;K103N;V106A;V106M;V179E;V90I;Y181C;Y188C;Y188L 53;86;37;44;44;60;31;67;74;74 58;91;42;51;51;65;35;72;81;81 NNRTI 6 11 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The common minority NNRTI mutations detected were V106M, V179T and G190A (3/20 each), followed by E138K and Y181C (2/20 each), and K101P, K103N, V108I, E138A, V179D, A190E and H221Y (1/20 each). 2018 African journal of laboratory medicine Result HIV A190E;E138A;E138K;G190A;H221Y;K101P;K103N;V106M;V108I;V179D;V179T;Y181C 166;152;98;67;176;131;138;50;145;159;57;108 171;157;103;72;181;136;143;55;150;164;62;113 NNRTI 20 25 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The minority PI mutations detected in three of the samples were M46I (2/20) and D30N (1/20) (Table 2). 2018 African journal of laboratory medicine Result HIV D30N;M46I 80;64 84;68 PI 13 15 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The most common minority NRTI mutation was K65R (6 of 20), followed by M184I (2 of 20, Table 2). 2018 African journal of laboratory medicine Result HIV K65R;M184I 43;71 47;76 NRTI 25 29 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The SNP frequency for K65R ranged from 0.7% to 2.5% of the sequence reads in these six patients and both mutant alleles of AGG and AGA were detected in these HIV-1 subtype C-positive samples. 2018 African journal of laboratory medicine Result HIV K65R 22 26 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. A total of 436 patients starting lamivudine-based DT were selected, of which 349 (80%) did not have the M184V mutation and 87 (20%) did have the M184V mutation, according to the hGRT (patients' baseline characteristics in Table 1). 2018 Open forum infectious diseases Result HIV M184V;M184V 104;145 109;150 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. At a further sensitivity analysis using a broader definition of viral blip (51-999 cp/mL; see the "Methods"), these occurred in 20 of 335 (6%) M184V- and 13 of 83 (16%) M184V+ patients (based on the hGRT classification). 2018 Open forum infectious diseases Result HIV M184V;M184V 143;169 148;174 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. At a further sensitivity analysis using the more stringent definition of virological failure, as defined in the "Methods" and according to the hGRT, the probabilities of remaining free from virological failure in M184V+ and M184V- were similar (Supplementary Figure 1B). 2018 Open forum infectious diseases Result HIV M184V;M184V 213;224 218;229 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. At Cox regression analysis, adjusting for hepatitis C virus (HCV) serostatus, duration of viral suppression, M184V status, and GSS of the regimen, being on a DT regimen (adjusted hazard ratio [aHR], 0.33; 95% CI, 0.14-0.81; P = .015) was independently associated with a lower risk of virological failure, whereas HBsAg positivity predicted a higher risk of virological failure (aHR, 2.96; 96% CI, 1.17-7.45; P = .022). 2018 Open forum infectious diseases Result HIV M184V 109 114 HIV-HCV coinfections 61 64 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. At multivariable Cox regression analysis, HCV infection and presence of M184V at hGRT were independently associated with a higher risk of viral blips (Table 3). 2018 Open forum infectious diseases Result HIV M184V 72 77 HIV-HCV coinfections 42 55 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. At the sensitivity analysis considering the last available genotypic resistance test for M184V status classification, similar results were obtained (Supplementary Figure 1D). 2018 Open forum infectious diseases Result HIV M184V 89 94 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Causes of treatment discontinuation were toxicity (55 in the M184V- group and 10 in the M184V+ group), virological failure (5 and 3, respectively), further simplification (23 and 6), and other (48 and 17). 2018 Open forum infectious diseases Result HIV M184V;M184V 61;88 66;93 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. During an overall 724 PYFU, 36 treatment discontinuations occurred in the M184V+ group during 153 PYFU, and 131 in the M184V- group during 571 PYFU (incidence, 23.5 and 22.9 per 100 PYFU, respectively; P = .332). 2018 Open forum infectious diseases Result HIV M184V;M184V 74;119 79;124 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Even DT with previous detection of M184V performed better than bPI monotherapy: 87.8% (95% CI, 78.4-97.2) vs 74.7% (95% CI, 65.9-92.3), but without a statistically significant difference (P = .099). 2018 Open forum infectious diseases Result HIV M184V 35 40 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In a different model also adjusting for baseline variables that were different between the 2 M184V groups (age, duration of viral suppression, CD4 at nadir, GSS of the accompanying drug), HCV infection (aHR, 2.96; 95% CI, 1.21-7.24; P = .017) and M184V at hGRT (aHR, 2.55; 95% CI, 0.98-6.62; P = .052) were confirmed as independently associated with viral blips. 2018 Open forum infectious diseases Result HIV M184V 247 252 HIV-HCV coinfections 188 201 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In a multivariate model adjusting for virological factors (duration of viral suppression, HIV-RNA at zenith, M184V, GSS of the accompanying drug), only higher HIV-RNA at zenith and lower GSS of the accompanying drug, but not M184V, were independently associated with virological failure, whereas another model including HBsAg status, time of viral suppression, age, sex, HIV-RNA at zenith, M184V, and GSS of the accompanying drug showed an independent association between HBsAg positivity and virological failure and confirmed that lower GSS is probably linked to virological failure (Table 2). 2018 Open forum infectious diseases Result HIV M184V;M184V;M184V 109;225;390 114;230;395 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In a sensitivity analysis, where only a subset of 85 patients were classified in the M184V+ group based on the last available genotypic resistance test, almost identical virological outcomes were observed (Supplementary Figure 1A). 2018 Open forum infectious diseases Result HIV M184V 85 90 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In an additional analysis selecting patients with equal to or less than 3 years of viral suppression, the respective 1- and 3-year probabilities of remaining free from virological failure were 100.0% and 67.7% in the M184V+ group and 97.3% an 96.2% in the M184V- group (P = .002) (Figure 1B). 2018 Open forum infectious diseases Result HIV M184V;M184V 217;256 222;261 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In the DT group, during 693 person-years of follow-up (PYFU; median follow-up, 1.3 years; interquartile range [IQR], 0.7-2.5), 24 virological failures were detected: 7 during 139 PYFU in M184V+ patients (incidence, 5.1; 95% confidence interval [CI], 2.2%-9.9% per 100 PYFU) and 17 during 554 PYFU in M184V- patients (incidence, 3.1; 95% CI, 1.8%-4.8% per 100 PYFU). 2018 Open forum infectious diseases Result HIV M184V;M184V 187;300 192;305 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In the subset of patients with viral suppression of <=6.6 years, the difference in the 3-year probability of remaining free of blips was even larger (M184V+ group: 69.4%; 95% CI, 50.6-88.2; M184V- group: 91.1%; 95% CI, 84.8-97.4; P < .001). 2018 Open forum infectious diseases Result HIV M184V;M184V 150;190 155;195 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In this subset, the 1- and 3-year probabilities of remaining free from virological failure were, respectively, 94.4% (95% CI, 87.0-101.8) and 82.9% (95% CI, 67.2-98.6) in the M184V+ group and 97.3% (95% CI, 95.1-99.5) and 92.5% (95% CI, 86.8-98.2) in the M184V- group (P = .080). 2018 Open forum infectious diseases Result HIV M184V;M184V 175;255 180;260 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The estimated probabilities of remaining free from treatment discontinuation were also similar in the 2 groups: at 1 year 84.9% (95% CI, 80.8-89.0) in the M184V- and 83.3% (95% CI, 74.4-91.7) in the M814V+ group; at 3 years 44.6% (95% CI, 37.2-53.0) in the M184V- group and 48.8% (95% CI, 32.9-64.7) in the M184V+ group (P = .847) (Figure 1C). 2018 Open forum infectious diseases Result HIV M184V;M184V;M184V;M814V 155;257;307;199 160;262;312;204 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The estimated probabilities of remaining free of viral blips were lower in patients with previous detection of M184V: at 1 year 85.9% (95% CI, 76.7-95.1) vs 96.4% (95% CI, 94.2-98.6) and at 3 years 79.8% (95% CI, 67.8-91.8) vs 90.1% (95% CI, 84.0-96.2) in the M184V- group (P = .016) (Figure 1D). 2018 Open forum infectious diseases Result HIV M184V;M184V 111;260 116;265 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The estimated probability of remaining free from virological failure was comparable in the 2 groups: at 1 year 95.1% (95% CI, 89.6-100.6) in M184V+ and 96.2% (95% CI, 93.9-98.6) in M184V- patients; at 3 years 87.8% (95% CI, 78.4-97.2) in M184V+ and 91.9% (95% CI, 86.6-97.2) in M184V- patients (P = .323) (Figure 1A). 2018 Open forum infectious diseases Result HIV M184V;M184V;M184V;M184V 141;181;238;278 146;186;243;283 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The only predictor of treatment discontinuation at univariate analysis was HBsAg positivity (HR, 2.42; 95% CI, 1.06-5.54; P = .037), which was confirmed in a multivariate model (aHR, 2.28; 95% CI, 0.99-5.27; P = .053) adjusting for duration of viral suppression, age, sex, and M184V status. 2018 Open forum infectious diseases Result HIV M184V 277 282 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. To minimize the difference in duration of viral suppression before baseline between the groups, an analysis selecting patients with viral suppression of equal to or less than 6.6 years (the median duration of viral suppression in the M184V+ group) was performed (n = 308: 265 in the M184V- group and 43 in the M184V+ group). 2018 Open forum infectious diseases Result HIV M184V;M184V;M184V 234;283;310 239;288;315 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Viral blips occurred in 10 of 80 (13%) M184V+ patients during 112 PYFU and 18 of 332 (5%) M184V- patients during 502 PYFU. 2018 Open forum infectious diseases Result HIV M184V;M184V 39;90 44;95 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Virological failures were 4 on lamivudine plus atazanavir/r and 3 on lamivudine plus darunavir/r in the M184V+ group, 7 on lamivudine plus atazanavir/r, 5 on lamivudine plus darunavir/r, 3 on lamivudine plus lopinavir/r, and 2 on lamivudine plus dolutegravir in the M184V- group. 2018 Open forum infectious diseases Result HIV M184V;M184V 104;266 109;271 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. No major mutation to PI was identified; however, five isolates presented minor PI mutations (K20M: BRGO_CK4, subtype B; A71V: BRGO_CK600, subtype B; L10V: BRGO_CK496, subtype B; A71T and L33I: BRGO_CK311, subtype B; L10V: BRGO_CK117, subtype C). 2018 PloS one Result HIV A71T;A71V;K20M;L10V;L10V;L33I 178;120;93;149;216;187 182;124;97;153;220;191 PI;PI 21;79 23;81 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. This patient's isolate (subtype B, ID# BRGO_CK343) had mutations associated with nucleoside reverse transcriptase inhibitors/NRTI (T215F and M184V) and non-nucleoside reverse transcriptase inhibitors/NNRTI (G190S). 2018 PloS one Result HIV G190S;M184V;T215F 207;141;131 212;146;137 NNRTI;NRTI;NNRTI;NRTI 152;81;200;125 188;113;205;129 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. Transmitted drug resistance was identified in one (age 29) ARV-naive female crack user that harbored virus with mutations to NRTI (M41L, T125C). 2018 PloS one Result HIV M41L;T125C 131;137 135;142 NRTI 125 129 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In contrast, the two MDR complexes with A62V, as well as the A62V mutant, had a reduced replication capacity compared to that of wt virus (Figure 3). 2018 Viruses Result HIV A62V;A62V 40;61 44;65 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In the absence of AZT, the A62V mutant alone had significantly reduced viral replication fitness, while the T69SSS insertion complex with A62V had a non-statistically significant decrease in fitness (Figure 5A). 2018 Viruses Result HIV A62V;A62V;T69SSS 27;138;108 31;142;114 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In the presence of AZT, all MDR mutant complexes, except for the T69SSS insertion complex without A62V, had a statistically significant increase in virus fitness (Figure 5B). 2018 Viruses Result HIV A62V;T69SSS 98;65 102;71 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In this assay, all four MDR mutants (i.e., Q151M complex with or without A62V, and the T69SSS insertion complex with or without A62V) were found to have a lower mutant frequency relative to that of the wt virus in the absence of AZT (Figure 2A). 2018 Viruses Result HIV A62V;A62V;Q151M;T69SSS 73;128;43;87 77;132;48;93 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Interestingly, the MDR mutants without the A62V mutation had the lowest observed mutant frequencies (i.e., roughly half that of HIV-1 wt), which was significantly different from those of MDR complex mutants, including the A62V mutation. 2018 Viruses Result HIV A62V;A62V 43;222 47;226 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Predictably, the A62V mutant alone had reduced fitness. 2018 Viruses Result HIV A62V 17 21 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The A62V mutant was observed to have the highest susceptibility to AZT with a 1.76-fold decrease in virus replication relative to that of the wt virus in the absence of AZT. 2018 Viruses Result HIV A62V 4 8 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The A62V mutant was observed to have the lowest replication capacity of the viruses analyzed. 2018 Viruses Result HIV A62V 4 8 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The fitness differences of the Q151M complex and T69SSS insertion complex mutants without A62V were not significant. 2018 Viruses Result HIV A62V;Q151M;T69SSS 90;31;49 94;36;55 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The mutant frequency of the MDR mutants (except for the T69SSS complex without A62V, which was significantly lower) was restored to wt levels under the pressure of AZT. 2018 Viruses Result HIV A62V;T69SSS 79;56 83;62 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The mutant frequency of virus variants harboring the A62V alone was further increased (i.e., 1.9-fold) in the presence of AZT relative to the wt virus in the absence of AZT. 2018 Viruses Result HIV A62V 53 57 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The observed virus mutant frequency of the A62V mutant alone was the highest (1.25-fold) of all mutants tested relative to the wt virus, as anticipated based upon previous observations. 2018 Viruses Result HIV A62V 43 47 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The Q151M complex and T69SSS insertion complex mutants with A62V had an AZT drug-susceptibility phenotype comparable to that of the wt virus. 2018 Viruses Result HIV A62V;Q151M;T69SSS 60;4;22 64;9;28 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The two MDR complex mutants without A62V were observed to have the highest level of drug susceptibility, with the T69SSS insertion complex having the highest fold increase (Figure 4). 2018 Viruses Result HIV A62V;T69SSS 36;114 40;120 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Two of the MDR complex mutants:the Q151M complex without A62V, and the T69SSS complex without A62V:each had an improved replication capacity compared to that of the wt virus, with the T69SSS complex without A62V mutant having the highest increase in replication capacity (Figure 3). 2018 Viruses Result HIV A62V;A62V;A62V;Q151M;T69SSS;T69SSS 57;94;207;35;71;184 61;98;211;40;77;190 30056211 Binding of host factors to stabilized HIV-1 capsid tubes. Contrary to the wild type TRIM5alphahu protein, TRIM5alphahu-R332P binds to capsid and restrict HIV-1. 2018 Virology Result HIV R332P 61 66 Capsid 76 82 30056211 Binding of host factors to stabilized HIV-1 capsid tubes. The HIV-1 capsid protein bearing changes A14C and E45C assembled into wild type tubes. 2018 Virology Result HIV A14C;E45C 41;50 45;54 Capsid 10 16 30056211 Binding of host factors to stabilized HIV-1 capsid tubes. To develop a capsid-binding assay with washing steps, we took advantage of the HIV-1 capsid mutations A14C and E45C. 2018 Virology Result HIV A14C;E45C 102;111 106;115 Capsid;Capsid 13;85 19;91 30056211 Binding of host factors to stabilized HIV-1 capsid tubes. To this end, we simultaneously tested the binding of human TRIM5alpha (TRIM5alphahu) bearing the mutation R332P to in vitro assembled HIV-1 CA-NC complexes and stabilized HIV-1 capsid tubes. 2018 Virology Result HIV R332P 106 111 Capsid;NC;Capsid 177;143;140 183;145;142 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. Major NRTI mutations were detected in 11 patient samples, which included M184V (n=6), M41L (n=3), D67N (n=2), K219Q (n=3) and T215F (n=2). 2018 The Pan African medical journal Result HIV D67N;K219Q;M184V;M41L;T215F 98;110;73;86;126 102;115;78;90;131 NRTI 6 10 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. They included K103N (n=10), G190A (n=1), Y181C (n=1) and Y188L (n=1) (Table 2). 2018 The Pan African medical journal Result HIV G190A;K103N;Y181C;Y188L 28;14;41;57 33;19;46;62 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. All five proline substitutions (S553P, N554P, L555P, Q562P, and Q563P) were compatible within the 16055 NFL backbone (Figure S3A in Supplementary Material), displaying a homogenous trimer peak by SEC. 2018 Frontiers in immunology Result HIV L555P;N554P;Q562P;Q563P;S553P 46;39;53;64;32 51;44;58;69;37 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Among the five substitutions, L555P resulted in ordered trimer production with slightly higher percentage of trimers in a closed native-like conformation (Figures S1B-D in Supplementary Material). 2018 Frontiers in immunology Result HIV L555P 30 35 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Antigenicity analysis by BLI and ELISA showed that L555P substitution improved the antigenic profile of 16055 NFL trimers, revealing increased recognition by the trimer-specific V2-apex-directed bNAbs (PGT145, PGDM1400, and PG16) and V3-targeting bNAb (PGT128), but little-to-no detectable binding by the non-NAbs (F105, GE136, 17b, and 447-52D) (Figure 2D; Figures S3E,F in Supplementary Material; Tables 2 and 3). 2018 Frontiers in immunology Result HIV L555P 51 56 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. As described above, the L555P substitution and the new CC2 inter-protomer disulfide bond improved the NFL trimer design, separately. 2018 Frontiers in immunology Result HIV L555P 24 29 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Because the HR1 region is relatively conserved among Env from different clades, we determined whether the P substitutions identified in the BG505 NFL context could be transferred to the clade C 16055 NFL, which is inefficient in its original I559P design in terms of yielding a high percentage of native-like trimers. 2018 Frontiers in immunology Result HIV I559P 242 247 Env 53 56 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. BG505 NFL L555P trimers exhibited a similar antigenic profile compared to BG505 NFL I559P (Figure S1F in Supplementary Material; Tables 2 and 3). 2018 Frontiers in immunology Result HIV I559P;L555P 84;10 89;15 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Comparable antigenicity profiles were similarly detected for BG505 NFL TD 2CC+ D4K L555P and I559P trimers (Figures S6F,G in Supplementary Material), consistent with trimer integrity. 2018 Frontiers in immunology Result HIV I559P;L555P 93;83 98;88 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Differential scanning calorimetry analysis revealed that the Tms of these trimers were over 80 C for both NFL TD 2CC+ D4K L555P and I559P, displaying an increase of over 21 C for 16055 NFL TD 2CC+ D4K and over 14 Cfor BG505 NFL TD 2CC+ D4K, relative to the "first generation" NFL I559P trimers (Figure 4D; Figure S6E in Supplementary Material). 2018 Frontiers in immunology Result HIV I559P;I559P;L555P 132;280;122 137;285;127 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. DSC analysis revealed that the L555P substitution generated more homogenous 16055 NFL trimers, with comparable thermostability, compared to the I559P change (Figure 2B; Figure S3C in Supplementary Material). 2018 Frontiers in immunology Result HIV I559P;L555P 144;31 149;36 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Following cleavage by rEK, 16055 NFL TD 2CC+ D4K L555P and I559P trimers showed single sharp trimer peaks on SEC (Figure 5A) with >94% of the trimers in a closed native-like conformation as resolved by NS-EM (Figure 5B). 2018 Frontiers in immunology Result HIV I559P;L555P 59;49 64;54 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Following negative selection, the yield of the 16055 NFL L555P trimers were increased compared to the original I559P trimers (Table 1). 2018 Frontiers in immunology Result HIV I559P;L555P 111;57 116;62 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Following rEK cleavage, the 16055 NFL TD 2CC+ D4K L555P and I559P trimers displayed increased recognition by the cleavage-sensitive bNAbs VRC34 and PGT151, while retaining similar levels of recognition by bNAbs targeting other epitopes (2G12, VRC01, and PGT128) (Figure 5E; Figure S8A in Supplementary Material). 2018 Frontiers in immunology Result HIV I559P;L555P 60;50 65;55 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. For head-to-head comparison, we generated two versions of NFL TD 2CC+ D4K trimers in 16055 and BG505 backbone, one containing the original I559P substitution and another possessing the identified L555P substitution. 2018 Frontiers in immunology Result HIV I559P;L555P 139;196 144;201 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. From the IP results, we identified a new cysteine pair (A501C-L663C, designated here as "CC2") showing favorable recognition by PGT145, VRC06, and PGT151, and low-level recognition by F105 (data not shown). 2018 Frontiers in immunology Result HIV A501C;L663C 56;62 61;67 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. In contrast, the 16055 NFL I559P SEC peak contained only small fractions of trimers (Figure 2A; Figure S3B in Supplementary Material), as previously reported. 2018 Frontiers in immunology Result HIV I559P 27 32 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. In total, we interrogated 36 residues in HR1 (Figure 1A) and found that at least five substitutions (S553P, N554P, L555P, Q562P, and Q563P) displayed favorable features based upon trimer-specific bNAb recognition compared to that of the non-neutralizing mAb, F105, in the oligomeric mixture (Figure S1A in Supplementary Material). 2018 Frontiers in immunology Result HIV L555P;N554P;Q562P;Q563P;S553P 115;108;122;133;101 120;113;127;138;106 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Regardless of the P substitution used, the combinatorial design in 16055 dramatically increased the yield of well-ordered trimers by over 13-fold compared to original 16055 NFL I559P (Table 1). 2018 Frontiers in immunology Result HIV I559P 177 182 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Similar antigenic profile was observed for BG505 NFL TD 2CC+ D4K L555P and I559P trimers after cleavage as well (Figures S7E and S8B in Supplementary Material). 2018 Frontiers in immunology Result HIV I559P;L555P 75;65 80;70 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Similar results were observed for BG505 NFL TD 2CC+ D4K L555P and I559P trimers (Figures S7A,B in Supplementary Material). 2018 Frontiers in immunology Result HIV I559P;L555P 66;56 71;61 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Similar results were obtained for BG505 NFL TD 2CC+ D4K L555P and I559P trimers (Figure S7C in Supplementary Material). 2018 Frontiers in immunology Result HIV I559P;L555P 66;56 71;61 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Similar SEC profiles were observed for BG505 NFL TD 2CC+ D4K L555P and I559P (Figure S6A in Supplementary Material). 2018 Frontiers in immunology Result HIV I559P;L555P 71;61 76;66 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Taken together, these analyses demonstrated that the combination of L555P, CC2, TD CC+, and engineered post-expression cleavage site, preserve the pre-fusion state of the NFL trimers with improved trimer formation, biophysical properties, and antigenicity. 2018 Frontiers in immunology Result HIV L555P 68 73 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Taken together, these data indicate that the new cysteine pair A501C-L663C (CC2) formed inter-protomer disulfide bonds, increasing the thermostability and antigenicity of NFL trimers derived from different clades. 2018 Frontiers in immunology Result HIV A501C;L663C 63;69 68;74 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Taken together, these data show that the L555P substitution is comparable to, or improved, relative to the original I559P substitution regarding to form well-ordered, homogenous, and stable NFL trimers. 2018 Frontiers in immunology Result HIV I559P;L555P 116;41 121;46 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The 16055 and BG505 NFL TD 2CC+ D4K L555P and I559P variants were purified by lectin-affinity chromatography, followed by SEC. 2018 Frontiers in immunology Result HIV I559P;L555P 46;36 51;41 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The NFL TD 2CC+ D4K L555P and I559P trimers were highly stable in solution, displaying no significant degradation at 37 C for 30 h indicated by gel analysis (data not shown). 2018 Frontiers in immunology Result HIV I559P;L555P 30;20 35;25 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The original NFL trimer design contains the I559P mutation to disfavor the post-fusion state. 2018 Frontiers in immunology Result HIV I559P 44 49 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The SEC trimer peak of 16055 NFL TD 2CC+ D4K I559P was much sharper than that of 16055 NFL TD 2CC+ D4K L555P, indicating the I559P substitution is more compatible with these modifications compared to L555P (Figure 4A). 2018 Frontiers in immunology Result HIV I559P;I559P;L555P;L555P 45;125;103;200 50;130;108;205 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The Tms of cleaved BG505 NFL TD 2CC+ D4K L555P and I559P trimers were 81.6 and 81.0 C, respectively, with 0.7 and 0.6 C increases over their uncleaved counterparts (Table 1). 2018 Frontiers in immunology Result HIV I559P;L555P 51;41 56;46 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The Tms of the cleaved 16055 NFL TD 2CC+ D4K L555P and I559P trimers were 82.8 and 82.6 C, respectively, displaying 2.6 and 2.5 C increases compared to their uncleaved counterparts. 2018 Frontiers in immunology Result HIV I559P;L555P 55;45 60;50 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The trimer peak on SEC was slightly shifted "to the right" for 16055 NFL L555P design, consistent with improved trimer formation and yield (Table 1). 2018 Frontiers in immunology Result HIV L555P 73 78 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. There was no significant difference of thermostability between NFL TD 2CC+ D4K L555P and I559P, but there was over a 3 C gain for NFL TD 2CC+ D4K compared to their corresponding NFL TD CC+ trimers, indicating the addition of CC2 increased thermal stability (Table 1). 2018 Frontiers in immunology Result HIV I559P;L555P 89;79 94;84 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Thermostability analysis by DSC of the five trimer variants revealed that the BG505 NFL L555P trimer was slightly more stable than BG505 NFL I559P trimer, displaying a 1 C increase in Tm (Figure S1E in Supplementary Material; Table 1). 2018 Frontiers in immunology Result HIV I559P;L555P 141;88 146;93 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. To reduce the flexibility and increase the stability of the first generation of NFL I559P trimers, we sought to identify additional internal disulfide pairs to stabilize NFL trimers. 2018 Frontiers in immunology Result HIV I559P 84 89 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Under reducing and non-reducing conditions, by SDS-PAGE analysis, the NFL I559P (without CC2) trimer proteins migrated as gp140 monomer. 2018 Frontiers in immunology Result HIV I559P 74 79 gp140 122 127 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Under reducing conditions, cleaved 16055 NFL TD 2CC+ D4K L555P and I559P proteins migrated as two bands, gp120 and gp41, whereas the uncleaved proteins migrated as a single gp140 band (Figure 5C), indicating the trimers were completely cleaved by rEK. 2018 Frontiers in immunology Result HIV I559P;L555P 67;57 72;62 gp120;gp140;gp41 105;173;115 110;178;119 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. We first assessed these potential new disulfide linkages in the original JRFL NFL I559P context. 2018 Frontiers in immunology Result HIV I559P 82 87 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. We used a panel of bNAbs and non-neutralizing Abs to assess the antigenicity changes of 16055 NFL TD 2CC+ D4K L555P and I559P trimers after cleavage by ELISA and BLI. 2018 Frontiers in immunology Result HIV I559P;L555P 120;110 125;115 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. We used the previously described panel of bNAbs and non-neutralizing Abs to assess the antigenicity of 16055 NFL TD 2CC+ D4K L555P and I559P trimers by ELISA and BLI, revealing that both trimer variants were recognized comparably by the trimer-specific bNAbs with no detectable recognition by the non-neutralizing Abs tested (Figure 4E; Figure S5 in Supplementary Material; Tables 2 and 3). 2018 Frontiers in immunology Result HIV I559P;L555P 135;125 140;130 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Also, other DRM such as K70R (5.56%), K219Q (5.56%), T69D (5.56%), Y115F (5.56%) and K65R (5.56%) were detected with equal rates in mothers and were associated with resistance to (AZT, 3TC, TDF), 3TC, DDI, ABC and 3TC respectively. 2018 Journal of public health in Africa Result HIV K219Q;K65R;K70R;T69D;Y115F 38;85;24;53;67 43;89;28;57;72 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Among the mutations identified, M184V was more predominant and was more frequent in mothers (27.78%) than in infants (22.22%). 2018 Journal of public health in Africa Result HIV M184V 32 37 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. G190A and K101Q/E were more frequent in mothers (16.67% and 16.67% respectively) than in infants (5.56% and 5.56%) and conferred resistance to NVP and EFV. 2018 Journal of public health in Africa Result HIV K101E;K101Q;G190A 10;10;0 17;17;5 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. In contrast, Y115F (5.56%) and K65R (5.56%) were identified only in infants and conferred resistance to ABC and 3TC respectively. 2018 Journal of public health in Africa Result HIV K65R;Y115F 31;13 35;18 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. In the NNRTI group, Y181C was more prevalent in infants (22.22%) than in mothers (5.56%) and conferred resistance to NVP and EFV. 2018 Journal of public health in Africa Result HIV Y181C 20 25 NNRTI 7 12 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. K103N was detected more in children (11.1%) than in mothers but did not confer resistance to ARV used. 2018 Journal of public health in Africa Result HIV K103N 0 5 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Other mutations such as P225H and 227L were identified only in mothers and conferred resistance to NVP (Figure 1B). 2018 Journal of public health in Africa Result HIV P225H 24 29 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Other mutations such as T215F/Y and D67N/E were also more prevalent in mothers (16.67% and 11.11% respectively) than in infants (5.56% and 5.56% respectively) (Table 3). 2018 Journal of public health in Africa Result HIV D67E;D67N;T215F;T215Y 36;36;24;24 42;42;31;31 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. T69Sinsertion, V75M, and L210W were detected only in mothers but did not confer resistance to drugs used (Figure 1A). 2018 Journal of public health in Africa Result HIV L210W;T69Sins;V75M 25;0;15 30;13;19 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. The drugs affected by these mutations were AZT (T215F/Y, D67N/E); 3TC (M184V, T215F/Y, D67N/E), FTC (M184V), ABC (M184V) and TDF (T215F/Y). 2018 Journal of public health in Africa Result HIV D67E;D67E;D67N;D67N;M184V;M184V;M184V;T215F;T215F;T215F;T215Y;T215Y;T215Y 57;87;57;87;71;101;114;48;78;130;48;78;130 63;93;63;93;76;106;119;55;85;137;55;85;137 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. Although Vpr WT suppresses L1 retrotransposition activities from both pYX014 and pYX017, the inhibitory effect of Vpr (H71R) was significantly relieved compared with that of Vpr (WT) (Figure 3E and F), suggesting that Vpr suppresses L1 mobility in a cell cycle dependent manner. 2018 Nucleic acids research Result HIV H71R 119 123 Vpr;Vpr;Vpr;Vpr 9;114;174;218 12;117;177;221 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. As a control, we observed similar levels of protein expression for both Vpr (WT) and the mutant Vpr (H71R) in transfected cells (Figure 3D). 2018 Nucleic acids research Result HIV H71R 101 105 Vpr;Vpr 72;96 75;99 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. Consistent with the previous report, we confirmed that wild-type Vpr (WT) arrested cell cycle at G2 (Figure 3A and B), while the H71R mutant failed to arrest cell cycle (Figure 3C). 2018 Nucleic acids research Result HIV H71R 129 133 Vpr 65 68 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. Consistent with the result of L1 retrotransposition activity with Vpr H71R (Figure 3E and F), Vpr H71R had a marginal effect on the ORF2 RT activity compared with that of Vpr WT (Figure 9B). 2018 Nucleic acids research Result HIV H71R;H71R 70;98 74;102 Vpr;Vpr;Vpr;RT 66;94;171;137 69;97;174;139 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. Similarly, Vpr and p21 did not suppress ORF1p when expressed from plasmids pJM101/L1.3 and pJM105/L1.3, which respectively contain WT and ORF2p RT-mutant (D702A) human L1.3 element in a pCEP4 backbone vector (Figure 7A and B). 2018 Nucleic acids research Result HIV D702A 155 160 Vpr;RT 11;144 14;146 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. To this end, we used a mutant Vpr (H71R) unable to arrest cell cycle. 2018 Nucleic acids research Result HIV H71R 35 39 Vpr 30 33 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Clinical isolates that failed to develop resistance with DTG, BIC, or CAB, including 14514, 10387, 10249, and 14515, acquired only T66I (n = 3) or E92Q (n = 1) singleton mutations with EVG at weeks 36 or 46. 2018 Retrovirology Result HIV E92Q;T66I 147;131 151;135 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Emergent high-level resistance to RAL were associated with the Y143R/G and Q148R pathways. 2018 Retrovirology Result HIV Q148R;Y143G;Y143R 75;63;63 80;70;70 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. For isolate 5326, the progressive accumulation of Q148K/G140S/G147GS resulted in increasingly high cross-resistance to CAB, RAL and EVG while retaining susceptibility to DTG and BIC (Table 3). 2018 Retrovirology Result HIV G140S;G147G;G147S;Q148K 56;62;62;50 61;68;68;55 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. For isolate 6343, the loss of T66I was accompanied by the acquisition of M50I with DTG (Table 7). 2018 Retrovirology Result HIV M50I;T66I 73;30 77;34 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. For the 96USSN20 isolate, the acquisition of T66I, S147G, Q146R, and S147G conferred viral escape from EVG at week 25. 2018 Retrovirology Result HIV Q146R;S147G;S147G;T66I 58;51;69;45 63;56;74;49 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. For the remaining seven isolates, CAB showed a lower barrier to resistance than DTG and BIC, with the acquisition of Q148R/K + 3 mutations in two isolates (Table 3). 2018 Retrovirology Result HIV Q148K;Q148R 117;117 124;124 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Genotypic analysis showed the switch of EVG-resistant strains (n = 6) to DTG, BIC, CAB or a no drug control for 27 weeks resulted in the loss of the T66I (3/6 selections) or Q146R (1/6) substitutions associated with primary resistance to EVG (Table 7). 2018 Retrovirology Result HIV Q146R;T66I 174;149 179;153 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In contrast, patient-derived pNL4-3 recombinant strains showed a high genetic barrier to resistance for DTG, BIC, and CAB, both in the presence or absence of E157Q. 2018 Retrovirology Result HIV E157Q 158 163 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In contrast, the loss of T66I in 14624 was accompanied by the acquisition of L74M/E138K/S147G/M154IM and L74M/G140GS/S147G at week 27 with DTG and CAB, respectively. 2018 Retrovirology Result HIV E138K;G140G;G140S;L74M;L74M;M154I;M154M;S147G;S147G;T66I 82;110;110;77;105;94;94;88;117;25 87;116;116;81;109;100;100;93;122;29 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In contrast, the respective first appearance of R263K or S153F mutations by 96USSN20 and 5326 viral strains with CAB at weeks 8, was followed by the serial accumulation of mutations along the Q148K/R resistance pathway leading to viral escape by week 48. 2018 Retrovirology Result HIV Q148K;Q148R;R263K;S153F 192;192;48;57 199;199;53;62 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In our previous studies, drug selections with the subtype C 4742 strain, the G118R resistance pathway arose with DTG and the Merck investigational MK2048. 2018 Retrovirology Result HIV G118R 77 82 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In this study, 4742 developed no resistance with DTG and BIC, R263K with CAB, and E92V/R263K with EVG (Table 3). 2018 Retrovirology Result HIV E92V;R263K;R263K 82;62;87 86;67;92 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. It was noteworthy that strains harbouring the E157Q substitution showed a significantly attenuated development of resistance to RAL and EVG. 2018 Retrovirology Result HIV E157Q 46 51 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. One recombinant strain, E78004, acquired a Q148R resistance pathway under selective pressure with CAB. 2018 Retrovirology Result HIV Q148R 43 48 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Phenotypic drug susceptibility assays explored the potential impact of the E157Q substitution drug susceptibility to INSTIs (Table 6). 2018 Retrovirology Result HIV E157Q 75 80 INSTI 117 123 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Resistance codons Q146R and Q95R for this CRF002_AG isolate have been hitherto unreported. 2018 Retrovirology Result HIV Q146R;Q95R 18;28 23;32 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Resistance profiles associated with escape from EVG drug pressure were associated with T66I and the accumulation of major resistance including Q148R/K, E138K, and S147G. 2018 Retrovirology Result HIV E138K;Q148K;Q148R;S147G;T66I 152;143;143;163;87 157;150;150;168;91 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Resistance profiles to DTG, BIC and CAB developed along the R263K or S153F/Y pathway; resistance to EVG was limited to the acquisition of T66I or E92Q at week 46. 2018 Retrovirology Result HIV E92Q;R263K;S153F;S153Y;T66I 146;60;69;69;138 150;65;76;76;142 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Selection of strain E78004 with CAB resulted in high level resistance along a Q148R/E138K/G140GS/L74I pathway (Table 4). 2018 Retrovirology Result HIV E138K;G140G;G140S;L74I;Q148R 84;90;90;97;78 89;95;96;101;83 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Similarly, 96USSN20 and E78004 viruses developed resistance along a Q148R pathway leading to L74M/E138K/G148R/R263K and L74I/E138K/G140S/Q148R conferring cross-resistance to all INSTIs. 2018 Retrovirology Result HIV E138K;E138K;G140S;G148R;L74I;L74M;Q148R;R263K;Q148R 98;125;131;104;120;93;137;110;68 103;130;136;109;124;97;142;115;73 INSTI 178 184 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The 96USSN20 virus resistant to EVG (T66I, Q146R, and S147G) lost Q146R and acquired E138A and Q148R with DTG, BIC and CAB. 2018 Retrovirology Result HIV E138A;Q146R;Q146R;Q148R;S147G;T66I 85;43;66;95;54;37 90;48;71;100;59;41 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The acquisition of R263K with S153A by isolate 5326 conferred > 100-fold resistance to EVG. 2018 Retrovirology Result HIV R263K;S153A 19;30 24;35 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The appearance of Q148R/Q95KQ followed by Q148R/Q95KQ/E138EK resistant strains at weeks 18 and 26 resulted in moderate 2.5- and 11.3-fold resistance to CAB, while retaining susceptibility to DTG and BIC. 2018 Retrovirology Result HIV E138E;E138K;Q148R;Q95K;Q95Q;Q148R;Q95K;Q95Q 54;54;42;48;48;18;24;24 59;60;47;53;53;23;28;29 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The development of the G118R resistance was ascribed to a signature natural polymorphism at codon 118 in isolate 4742. 2018 Retrovirology Result HIV G118R 23 28 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The E157Q has also been observed in several persons failing INSTI-based regimens, including RAL and DTG. 2018 Retrovirology Result HIV E157Q 4 9 INSTI 60 65 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The E157Q mutation arose in a EVG and RAL selections in recombinant strains E78004 and E78060, respectively (Table 4). 2018 Retrovirology Result HIV E157Q 4 9 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The EVG-resistant 14947 variant T66I/E138K/S147G/Q148R variant accumulated S230N with BIC and DTG and L74M/S230N with CAB. 2018 Retrovirology Result HIV E138K;Q148R;S147G;T66I;L74M;S230N;S230N 37;49;43;32;102;75;107 42;54;48;36;106;80;112 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The EVG-resistant isolates 6343, 14637 and 5326, harbouring R263K, E157Q/R263K and S153A/R263K, showed residual susceptibility to DTG, BIC and CAB with no further acquisition of resistance mutations at week 27 (Table 7). 2018 Retrovirology Result HIV E157Q;R263K;R263K;R263K;S153A 67;73;60;89;83 72;78;65;94;88 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The first appearance of Q148K as a solitary mutation under CAB pressure in clinical isolate 5326) and recombinant strain E78004 at weeks 18 conferred low-level (< 2-3 fold) resistance to CAB, DTG, BIC and RAL with moderate (12-32-fold) reduced susceptibility to EVG (Tables 5, 6). 2018 Retrovirology Result HIV Q148K 24 29 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The hypersensitivity of viruses to E157Q suggests that this mutation is a compensatory mutation, commonly selected with INSTIs with minimal effects on drug susceptibility. 2018 Retrovirology Result HIV E157Q 35 40 INSTI 120 126 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The integrase E157Q substitution has been described as a common natural polymorphism present in 2.3% of HIV-1 viral sequences, including 3.8% and 6.0% of treatment-naive patients with subtype B and subtype CRF02_AG subtype infections, respectively (Los Alamos database, www.hiv.lanl.gov, accessed June 8, 2018). 2018 Retrovirology Result HIV E157Q 14 19 IN 4 13 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The other isolates accumulated 2-4 secondary drug resistance mutations along the T66I and E92QV pathways, leading to viral escape and EVG dose escalations to 1-5 microM. 2018 Retrovirology Result HIV E92Q;E92V;T66I 90;90;81 95;95;85 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The outgrowth of the L74I/E138K/G140GS, Q148R showed 25-, 5.3-, 87-, 57- and > 100-fold cross-resistance to DTG, BIC, CAB, EVG, and RAL, respectively. 2018 Retrovirology Result HIV E138K;G140G;G140S;L74I;Q148R 26;32;32;21;40 31;38;38;25;45 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The Q146P is a reported mutation selected in vitro with EVG, reducing RAL and EVG susceptibility by 10-fold.The Q95K is rare nonpolymorphic accessory resistance mutation conferring little if any effect on drug susceptibility to INSTIs. 2018 Retrovirology Result HIV Q146P;Q95K 4;112 9;116 INSTI 228 234 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The resistant variant of 5326 amplified at week 48 under selective CAB pressure, harbouring L74M/G140S/S147G/Q148K mutations showed high-level cross-resistance to all INSTIs, including DTG, BIC, CAB, EVG and RAL (Table 5). 2018 Retrovirology Result HIV G140S;L74M;Q148K;S147G 97;92;109;103 102;96;114;108 INSTI 167 173 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. This isolate developed Q146R/Q95KQ with DTG and BIC, a hitherto unreported profile for both drugs. 2018 Retrovirology Result HIV Q146R;Q95K;Q95Q 23;29;29 28;33;34 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. To assess the potential impact of E157Q on emergent resistance to INSTIs, recombinant viruses were constructed where patient-derived integrase were inserted on a pNL4-3Delta integrase background. 2018 Retrovirology Result HIV E157Q 34 39 IN;IN;INSTI 133;174;66 142;183;72 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. To date, very few data are available regarding virological response in patients harbouring E157Q-mutated viruses. 2018 Retrovirology Result HIV E157Q 91 96 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Two other variants, 14947 and 6343, acquired R263K/S153A and S153Y/G163R variants. 2018 Retrovirology Result HIV G163R;R263K;S153A;S153Y 67;45;51;61 72;50;56;66 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Two viral variants 5326 and 96USSN20 variants acquired complex L74M/G140S/S147G/Q148K and L74M/E138K/Q148R/R263K resistant species allowing for drug-dose escalations to 1 and 0.5 microM by week 46, respectively. 2018 Retrovirology Result HIV E138K;G140S;L74M;L74M;Q148K;Q148R;R263K;S147G 95;68;63;90;80;101;107;74 100;73;67;94;85;106;112;79 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Viral strains E78004 and E78060 acquiring the E157Q under EVG and RAL showed hypersensitivity to DTG, BIC, CAB, consistent with the observed attenuated development of resistance to RAL and EVG of E157Q relative to wild-type recombinant strains. 2018 Retrovirology Result HIV E157Q;E157Q 46;196 51;201 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Viruses included recombinant strains with (n = 5) and without (n = 5) the E157Q substitution (n = 5) in integrase. 2018 Retrovirology Result HIV E157Q 74 79 IN 104 113 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. With BIC or DTG, the acquisition of solitary resistance mutations, including R263K (n = 8), S153Y/F (n = 3) or H51H/Y (n = 1) negatively impacted on viral fitness, precluding drug-dose escalations beyond 0.005-0.025 microM. 2018 Retrovirology Result HIV H51H;H51Y;R263K;S153F;S153Y 111;111;77;92;92 117;117;82;99;99 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. With BIC, T66I was lost and H51HY was acquired. 2018 Retrovirology Result HIV H51H;H51Y;T66I 28;28;10 33;33;14 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. With DTG and BIC, the acquisitions of solitary mutations, including R263K, H51Y, or S153F, conferred low-level resistance to DTG or BIC. 2018 Retrovirology Result HIV H51Y;R263K;S153F 75;68;84 79;73;89 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. With DTG, BIC and CAB, the predominant resistance profile included R263K (n = 11), R263K/M50I (n = 7), and S153Y/F (n = 5). 2018 Retrovirology Result HIV M50I;R263K;R263K;S153F;S153Y 89;67;83;107;107 93;72;88;114;114 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Analyses of >=100 cells per construct showed that SIVcol Nef promotes retargeting of Lck to the perinuclear region almost as efficiently as HIV-1 Nef, and this activity was not affected by the Y86F change (Fig 5F, right). 2018 PLoS pathogens Result HIV Y86F 193 197 Nef;Nef 57;146 60;149 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Both effects were attenuated but not fully disrupted by the Y86F mutation. 2018 PLoS pathogens Result HIV Y86F 60 64 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Confocal microscopy analyses confirmed that HIV-1 and SIVcol Nef relocalized GFP-tagged SERINC5 from the cell surface to intracellular structures (Fig 7A) and this effect was strongly attenuated by the Y86F mutation (Fig 7B; supplemental S1-S4 Movies). 2018 PLoS pathogens Result HIV Y86F 202 206 Nef 61 64 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. In agreement with previous reports, human SERINC3 had only modest inhibitory effects that were counteracted by wt NL4-3 and SIVcol Nef proteins but not by SIVcol Y86F or SIVmac239 Nef (Fig 2C). 2018 PLoS pathogens Result HIV Y86F 162 166 Nef;Nef 131;180 134;183 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. In agreement with the results obtained in transient transfection assays and in purified CD4+ T cells, the NL4-3, SIVmac239, SIVcol CGU1 and LL/AA Nefs Nefs significantly enhanced virion infectivity, while the SIVmac239 LL/AA and SIVcol Y86F Nefs had little if any effect (Fig 9B). 2018 PLoS pathogens Result HIV Y86F 236 240 Nef;Nef;Nef 146;151;241 150;155;245 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. In contrast, lack of Nef expression or expression of wt or Y86F mutant SIVcol Nef proteins was associated with lack of viral replication if cells were agitated. 2018 PLoS pathogens Result HIV Y86F 59 63 Nef;Nef 21;78 24;81 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. In contrast, wt SIVcol Nef but not the Y86F mutant or HIV-1 NA7 Nef induced significant colocalization of SERINC5 with PSMA5, a component of the 20S core proteasome complex (Fig 7D and 7E). 2018 PLoS pathogens Result HIV Y86F 39 43 Nef;Nef 23;64 26;67 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Infection of TZM-bl and P4-CCR5 reporter cells with these viral constructs showed that mutation of Y86F alone or in combination with Y87F strongly impaired the ability of SIVcol Nef to enhance virion infectivity, whereas alterations in Y residues at positions 28, 30, 46, 64, 80 and 87 had no significant effect (Fig 2B). 2018 PLoS pathogens Result HIV Y86F;Y87F 99;133 103;137 Nef 178 181 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Mutation of Y86F but not of YxxxLL to YxxxAA (LL/AA) impaired this effect. 2018 PLoS pathogens Result HIV Y86F 12 16 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Notably, the SIVcol CGU1 and LL/AA Nefs that counteract SERINC5 moderately increased infectious virus yield compared to the Y86F Nef during later time-points. 2018 PLoS pathogens Result HIV Y86F 124 128 Nef;Nef 35;129 39;132 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. On average, however, the levels of p24 production and CD4+ T cell depletion did not differ significantly between the wt and Y86F SIVcol Nef constructs (Fig 10A-10C). 2018 PLoS pathogens Result HIV Y86F 124 128 p24;Nef 35;136 38;139 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Signal intensity was significantly reduced by the Y86F mutation (Fig 7G) suggesting that this residue is required for efficient interaction between SIVcol Nef and SERINC5 at cellular membranes. 2018 PLoS pathogens Result HIV Y86F 50 54 Nef 155 158 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Similarly, both wt and Y86F SIVcol Nefs promoted the activity of NF-AT, albeit less effectively than the HIV-1 NA7 Nef (Fig 10E). 2018 PLoS pathogens Result HIV Y86F 23 27 Nef;Nef 35;115 39;118 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Substitution of Y86F disrupted the effect of SIVcol CGU1 Nef on all SERINC5 variants analyzed, while substitution of Y87F had negligible effects. 2018 PLoS pathogens Result HIV Y86F;Y87F 16;117 20;121 Nef 57 60 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. The activity of SIVcol Nef against Colobus tetherin was disrupted by the Y86F substitution (Fig 4B and 4C). 2018 PLoS pathogens Result HIV Y86F 73 77 Nef 23 26 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. The Y86F change attenuated this activity but mutant SIVcol Nef still remained as active as HIV-1 NL4-3 Nef. 2018 PLoS pathogens Result HIV Y86F 4 8 Nef;Nef 59;103 62;106 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. The Y86F mutation disrupted the high anti-SERINC5 activity of SIVcol CGU1 Nef, while Y87F had no significant effect. 2018 PLoS pathogens Result HIV Y86F;Y87F 4;85 8;89 Nef 74 77 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. The Y86F mutation significantly abrogated the ability of SIVcol Nef to prevent degradation, virion incorporation and down-modulation of SERINC5 (Fig 6A-6C). 2018 PLoS pathogens Result HIV Y86F 4 8 Nef 64 67 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. This effect was disrupted by mutation of YxxxLL to YxxxAA in the C-terminal region of SIVcol CGU1 Nef but hardly affected by substitution of Y86F or Y87F (Fig 5B). 2018 PLoS pathogens Result HIV Y86F;Y87F 141;149 145;153 Nef 98 101 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. To assess whether the ability of Nef to counteract SERINC5 enhances viral replication, we transduced pre-activated CD4+ T cells with HIV-1 NL4-3 expressing wt or Y86F SIVcol or control HIV-1 and SIVmac nef alleles. 2018 PLoS pathogens Result HIV Y86F 162 166 Nef;Nef 33;202 36;205 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. To clarify whether the Y86F mutation affects binding of SIVcol Nef to SERINC5, we used the mammalian-membrane two-hybrid assay (MaMTH) allowing to detect even transient interactions between membrane proteins in living human cells. 2018 PLoS pathogens Result HIV Y86F 23 27 Nef 63 66 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Western blot analyses showed that the Y86F mutation disrupts the ability of SIVcol Nef to counteract SERINC5 without altering Nef expression levels (Fig 2D). 2018 PLoS pathogens Result HIV Y86F 38 42 Nef;Nef 83;126 86;129 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. When the PBMC cultures were stimulated 6 days post-infection, the CGU1 and LL/AA SIVcol Nefs resulted in a phenotype intermediate between wt and nef-defective HIV-1, while the Y86F Nef had only marginal effects (Fig 9A, upper right). 2018 PLoS pathogens Result HIV Y86F 176 180 Nef;Nef;Nef 88;145;181 92;148;184 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. 4'-Fluoromethyl and 4'-ethyl moiety of FMAdA-TP and EtAdA-TP had good interaction with wild-type HIV-1 RT (M184), but these interactions were reduced with M184V substitution (Figures 6C and E). 2018 Cell chemical biology Result HIV M184V 155 160 RT 103 105 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. A114V, Y115A, and D185A mutations, which reduced the activity of HIV-1 RT by >90%, also critically decreased viral replication (Figures 5A, B). 2018 Cell chemical biology Result HIV D185A;Y115A;A114V 18;7;0 23;12;5 RT 71 73 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. As expected, seven of the 4'-NRTIs examined showed low IC50 values (fold increase from 0.06 to 0.9 compared with that against HIV-1WT) and none of them showed elevated level of resistance against HIV-1K65R (Table 1). 2018 Cell chemical biology Result HIV K65R 201 205 NRTI 29 34 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Based on the obtained results, we divided the 4'-NRTIs into two groups: (i) HIV-1M184V-active group, which includes 4'-NRTIs with the 4'-ethynyl or 4'-cyano moiety (e.g., EFdA, CAdA, and EdC), and (ii) HIV-1M184V-inactive group, which includes 4'-NRTIs with other 4'-moieties (e.g., 4'-fluoromethyl-2-amino-2'-deoxyadenosine [FMAdA], 4'-methyl-2-amino-2'-deoxyadenosine [MAdA], and VAdA) (Table 1 and Figure 1). 2018 Cell chemical biology Result HIV M184V 207 212 NRTI;NRTI;NRTI 49;119;247 54;124;252 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. In contrast, six 4'-NRTIs, including EFdA and CAdA, showed activity against HIV-1M184V, with IC50 values ranging from 4.4 to 356 nM (fold change between 0.6 and 22). 2018 Cell chemical biology Result HIV M184V 81 86 NRTI 20 25 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Next, we analyzed the interaction of FMAdA-TP (4'-fluoromethyl) and EtAdA-TP (4'-ethyl), which showed very potent activity against HIV-1WT but not against HIV-1 that contained M184V substitution (Table 1 and Table S2). 2018 Cell chemical biology Result HIV M184V 176 181 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Next, we examined the activity of the 4'-NRTIs against a drug-resistant HIV-1K65R variant because K65R is a TDF resistance-associated mutation that reportedly induces hypersensitivity to EFdA. 2018 Cell chemical biology Result HIV K65R 98 102 NRTI 41 46 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Next, we examined the activity of these compounds against an HIV-1 clone namely HIV-167-75,184,215, harboring seven mutations, D67Delta T69G, K70R, L74I, V75T, M184V, and T215F, derived from HIV-1EFdAR and obtained almost similar results as those obtained for HIV-1EFdAR (Table S2, right column). 2018 Cell chemical biology Result HIV K70R;L74I;M184V;T215F;T69G;V75T 142;148;160;171;136;154 146;152;165;176;140;158 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Next, we examined the effect of HIV-1 RT67-75 (containing D67Delta, T69G, K70R, L74I, and V75T mutations) and HIV-1 RTT215F on viral replication and found that these mutants only slightly affected viral replication kinetics (50% ~ 90% replication compared with that of HIV-1 expressing wild-type RT); moreover, replication was well maintained in HIV-1 harboring these mutants (Figure 5B). 2018 Cell chemical biology Result HIV K70R;L74I;T69G;V75T 74;80;68;90 78;84;72;94 RT;RT;RT 38;116;296 40;118;298 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Previously, we observed that EFdA showed only a slightly decreased activity (~6-fold decrease) against HIV-1M184V. 2018 Cell chemical biology Result HIV M184V 108 113 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Substitution of F160 with Alanine (F160A) resulted in the complete loss of the enzymatic activity of HIV-1 RT (HIV-1 RTF160A) (Figure 5A). 2018 Cell chemical biology Result HIV F160A 35 40 RT;RT 107;117 109;119 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. The EFdA-related derivatives also showed similar or slightly reduced activity (0.3~11.1 fold; Table 1) against HIV-1T215F. 2018 Cell chemical biology Result HIV T215F 116 121 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Therefore, we generated multiple HIV-1 clones containing some of the mutations present in the HIV-1EFdAR variant, such as HIV-1 clones harboring D67Delta, T69G, K70R, L74I, and V75T mutations (HIV-167-75); M184V mutation (HIV-1M184V); or T215F mutation (HIV-1T215F), by using site-directed-mutagenesis. 2018 Cell chemical biology Result HIV K70R;L74I;M184V;T215F;T69G;V75T 161;167;206;238;155;177 165;171;211;243;159;181 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. These results suggest that M184V is a key mutation that induces resistance to the 4'-NRTIs examined in the present study. 2018 Cell chemical biology Result HIV M184V 27 32 NRTI 85 90 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. We previously selected an HIV-1EFdAR variant harboring M41L, D67Delta, T69G, K70R, L74I, V75T, M184V, T215F, and K219Q mutations (Figure 2A). 2018 Cell chemical biology Result HIV K219Q;K70R;L74I;M184V;M41L;T215F;T69G;V75T 113;77;83;95;55;102;71;89 118;81;87;100;59;107;75;93 30219320 Genome-scale analysis of evolutionary rate and selection in a fast-expanding Spanish cluster of HIV-1 subtype F1. Regarding positively selected sites, nef H89F substitution (Table 1), which was located in CD8+ and CD4+ T cell human epitopes (nef positions 84-92, wild type sequence AVDLSHFLK), was significantly overrepresented in the transmission cluster (18/23 sequences) compared to the other HIV-1 F1 sequences (3/19; Fisher test: P < 0.001). 2018 Infection, genetics and evolution Result HIV H89F 41 45 Nef;Nef 37;128 40;131 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. M184 V mutation was found to be the most common mutation among this group of mothers. 2018 Virology journal Result HIV M184V 0 6 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Major DRAMs to NNRTIs seen in the Prophylaxis plus ART Group (Group 1) were K103 N, Y181C, M230 L and L100IL and the minor DRAMs to NNRTIs seen was A98G. 2018 Virology journal Result HIV A98G;K103N;L100I;L100L;M230L;Y181C 148;76;102;102;91;84 152;82;108;108;97;89 NNRTI;NNRTI 15;132 21;138 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. One minor drug resistance associated mutation, A98G, was seen in one patient in this group. 2018 Virology journal Result HIV A98G 47 51 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The major DRAMs to NRTIs seen in this group were M184 V, Y115F, K70R, K219E and M41 LM while the minor DRAMs to NRTIs seen were T215S, T215I and D67G. 2018 Virology journal Result HIV D67G;K219E;K70R;M184V;T215I;T215S;Y115F 145;70;64;49;135;128;57 149;75;68;55;140;133;62 NRTI;NRTI 19;112 24;117 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The major DRAMs to PIs seen in the group was I84V; the minor drug resistance mutations seen were A71V, L89 V and M46MV. 2018 Virology journal Result HIV A71V;I84V;L89V;M46M;M46V 97;45;103;113;113 101;49;108;118;118 PI 19 22 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The major drug resistance associated mutations to NRTIs seen among the Group 1 participants were M41 L, M184 V, M184MV, L74 V and T215Y with no minor drug resistant associated mutations to NRTIs in this group. 2018 Virology journal Result HIV L74V;M184M;M184V;M184V;M41L;T215Y 120;112;112;104;97;130 125;118;118;110;102;135 NRTI;NRTI 50;189 55;194 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The most common HIV-1 drug resistance associated mutations seen with the NNRTIs were K103 N, M230 L and A98G. 2018 Virology journal Result HIV A98G;K103N;M230L 104;85;93 108;91;99 NNRTI 73 79 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The most common TAM seen in this study were M41 L and T215Y. 2018 Virology journal Result HIV M41L;T215Y 44;54 49;59 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The most commonly seen drug resistant associated mutations to NRTIs in this group were M184 V, T215Y and M41 L. 2018 Virology journal Result HIV M184V;M41L;T215Y 87;105;95 93;110;100 NRTI 62 67 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. There were no major DRAMs to NNRTIs in this group though the minor drug resistance mutation, A98G, was seen in two of the patients. 2018 Virology journal Result HIV A98G 93 97 NNRTI 29 35 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Three major DRAMs to NNRTIs were seen in 3 patients among the drug-naive participants; these DRAMs were K103 N, V106A and E138A. 2018 Virology journal Result HIV E138A;K103N;V106A 122;104;112 127;110;117 NNRTI 21 27 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Thymidine analogue mutations (TAMs) were seen in this study; these were M41 L, K70R, L210 W, T215Y and K219E. 2018 Virology journal Result HIV K219E;K70R;L210W;M41L;T215Y 103;79;85;72;93 108;83;91;77;98 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Two major HIV-1 drug resistance associated mutations for NRTIs, M184 V and L210 W, were seen in two of the participants with one minor DRAMs to NRTIs, V75S, seen in one patient; one patient did not have any drug resistance mutation to NRTIs. 2018 Virology journal Result HIV L210W;M184V;V75S 75;64;151 81;70;155 NRTI;NRTI;NRTI 57;144;235 62;149;240 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. 3b), indicating that the Y135L mutation does not impair recognition by YF9-specific T cells. 2018 EBioMedicine Result HIV Y135L 25 30 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. 3d), indicating that the emergence of the Y135F mutant impairs the ability of YF9-specific CD8+ T cells to suppress the mutant virus in the HLA-B*35:01+ individuals. 2018 EBioMedicine Result HIV Y135F 42 47 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. A previous study had described 2 HLA-A*11:01-associated polymorphisms; Gag S126G and Nef T80D, an HLA-C*07:02-associated polymorphism Nef R71K, and an HLA-A*24:02-associated polymorphism Nef Y135F in Japanese donors (Supplementary Table 2). 2018 EBioMedicine Result HIV R71K;S126G;T80D;Y135F 138;75;89;191 142;80;93;196 Nef;Nef;Nef;Gag 85;134;187;71 88;137;190;74 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. All five Y135/Y135L-infected HLA-A*24:02+ individuals were responders to RF10 peptide (data not shown), whereas 21 of 27 Y135F-infected individuals showed responses to RF10 and/or RF10-2F. 2018 EBioMedicine Result HIV Y135L 14 19 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Effect of CD8+ T cell responses to the 3 epitopes on pVL in Y135F-infected individuals. 2018 EBioMedicine Result HIV Y135F 60 65 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Finally, we investigated the effect of the Nef Y135F mutation on pVL. 2018 EBioMedicine Result HIV Y135F 47 52 Nef 43 46 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Gag S126G, Nef T80D, and Nef R71K mutations did not accumulate in HLA-B*35:01+ Japanese individuals, whereas Nef Y135F was found in 61% of the cohort. 2018 EBioMedicine Result HIV R71K;S126G;T80D;Y135F 29;4;15;113 33;9;19;118 Nef;Nef;Nef;Gag 11;25;109;0 14;28;112;3 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Impact of Nef Y135F mutation on pVL in HIV-1-infected HLA-B*35:01+ individuals. 2018 EBioMedicine Result HIV Y135F 14 19 Nef 10 13 HIV infections 39 53 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. In addition, the Y135F-infected responders had significantly lower pVL than the Y135F-infected non-responders, although both had relatively high pVL. 2018 EBioMedicine Result HIV Y135F;Y135F 17;80 22;85 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. In contrast, the effect of these T cell responses was minimal in WT or Y135L-infected individuals, although responders to NY9 had a slightly lower pVL than non-responders. 2018 EBioMedicine Result HIV Y135L 71 76 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. In contrast, there was no difference in pVL between responders and non-responders infected with Y135/Y135L virus. 2018 EBioMedicine Result HIV Y135L 101 106 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. It is well known that the Y135F mutation is selected by RF10-specific T cells restricted by HLA-A*24:02. 2018 EBioMedicine Result HIV Y135F 26 31 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Responders to RY11 or VY10 had lower pVL than non-responders amongst Y135F-infected individuals although this was only statistically significant for RY11 and VY10. 2018 EBioMedicine Result HIV Y135F 69 74 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Since the Y135L mutation did not affect recognition by YF9-specific T cells, we assigned this mutation into the WT group. 2018 EBioMedicine Result HIV Y135L 10 15 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. The breadth of the T cell responses to these 3 peptides and YF9 showed a strong correlation with lower pVL in Y135F-infected individuals. 2018 EBioMedicine Result HIV Y135F 110 115 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. These findings together suggest that the Y135F mutation may impair the suppression of HIV-1 replication by YF9-specific T cells, even though the mutation is not driven by HLA-B*35:01. 2018 EBioMedicine Result HIV Y135F 41 46 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. These results suggest that T cells specific for these epitopes can suppress replication of the Y135F mutant virus. 2018 EBioMedicine Result HIV Y135F 95 100 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. This result raises the possibility that mutant-specific T cells can to some extent suppress replication of the Y135F virus. 2018 EBioMedicine Result HIV Y135F 111 116 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. To determine the effect of this mutation on the suppressive capacity of YF9-specific T cells, we compared pVL between individuals with YF9 responses infected with either Y135/Y135L or Y135F virus. 2018 EBioMedicine Result HIV Y135L;Y135F 175;184 180;189 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. To determine the role of HLA-B*35:01-restricted CD8+ T cells specific for the other 3 epitopes in Y135F-infected individuals, we compared pVL between those with and without responses to p17NY9, RTVY10, or NefRY11 epitope. 2018 EBioMedicine Result HIV Y135F 98 103 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. To determine whether HLA-A*24:02-restricted CD8+ T cells can affect HIV-1 control in B*35:01+ individuals, we compared pVL between Y135/Y135L-infected and Y135F-infected HLA-A*24:02+ or A*24:02- individuals but found no significant differences. 2018 EBioMedicine Result HIV Y135L;Y135F 136;155 141;160 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. We also found a Nef Y135L mutation in approximately 8% of the HLA-B*35:01+ individuals (data not shown) although this mutation did not appear to be associated with specific HLA alleles. 2018 EBioMedicine Result HIV Y135L 20 25 Nef 16 19 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. We investigated the effect of this mutation on pVL, but did not find any significant difference in pVL between those individuals carrying wild-type (WT) virus and those harboring the Nef Y81F mutant. 2018 EBioMedicine Result HIV Y81F 187 191 Nef 183 186 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. We investigated the frequencies of HIV variants containing Gag S126G, Nef T80D, Nef R71K, or Nef Y135F mutations in the HLA-B*35:01+ individuals. 2018 EBioMedicine Result HIV R71K;S126G;T80D;Y135F 84;63;74;97 88;68;78;102 Nef;Nef;Nef;Gag 70;80;93;59 73;83;96;62 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. We previously identified one HLA-B*35:01-associated polymorphism, Nef Y81F, which is in the NefRY11 epitope, amongst HIV-1-infected Japanese individuals. 2018 EBioMedicine Result HIV Y81F 70 74 Nef 66 69 HIV infections 117 131 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. We therefore investigated T cell responses to the RF10 peptide in Y135/Y135L-infected HLA-A*24:02+ individuals and responses to RF10 and RF10-2F peptides in subject infected with Y135F virus. 2018 EBioMedicine Result HIV Y135L;Y135F 71;179 76;184 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. When pVL was compared between Y135-infected or Y135L-infected (Y135/Y135L-infected) and Y135F-infected HLA-B*35:01+ individuals, those infected with the Y135F mutant had significantly higher pVL than those with Y135/Y135L. 2018 EBioMedicine Result HIV Y135L;Y135L;Y135F;Y135F;Y135L 68;216;88;153;47 73;221;93;158;52 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. When responses to these peptides were analyzed in relation to pVL, no significant differences were seen between responders and non-responders or between responders and HLA-A*24:02- individuals amongst those infected with Y135F virus. 2018 EBioMedicine Result HIV Y135F 221 226 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Y135/Y135L virus-infected responders had much lower pVL than Y135F virus-infected responders. 2018 EBioMedicine Result HIV Y135L;Y135F 5;61 10;66 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. G190A, E138A/G) were found concurrently both in viral RNA and proviral DNA, in two patients resistance mutations (M46I and G190E) were detected only in viral RNA, and in five patients archived transmitted drug resistance mutations (M230I, G73S, M184I, M46I, and A62V) in proviral DNA were identified. 2018 PloS one Result HIV A62V;E138A;E138G;G190E;G73S;M184I;M230I;M46I;M46I;G190A 262;7;7;123;239;245;232;114;252;0 266;14;14;128;243;250;237;119;256;5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. HIV-1 proviral DNA from sample G168 had two archived transmitted drug resistance mutations (M46I and M230I) the same is true for G020 (G73S and M230I). 2018 PloS one Result HIV G73S;M230I;M230I;M46I 135;101;144;92 140;106;149;97 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. However, its presence reduces ETR and RPV susceptibility by about 2-fold and hence the presence of E138A prior to therapy may reduce the antiviral activity of RPV. 2018 PloS one Result HIV E138A 99 104 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. NRTIs related mutations M184I and A62V were only found in proviral DNA (Table 2). 2018 PloS one Result HIV A62V;M184I 34;24 38;29 NRTI 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. Out of the 5 patients with drug resistant associated mutations in proviral DNA, three had >=2 APOBEC3G/F signature mutations (M184I and M230I) in reverse transcriptase region with G-to-A mutations. 2018 PloS one Result HIV M184I;M230I 126;136 132;141 RT 146 167 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. Please note that, E138A is a polymorphic change depending on subtype and could occur in 0.5% to 5% of viruses from treatment naive patients. 2018 PloS one Result HIV E138A 18 23 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. Positions V82I (PR) and A98S (RT) were most common polymorphic alterations in both compartments (Table 5). 2018 PloS one Result HIV A98S;V82I 24;10 28;14 PR;RT 16;30 18;32 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. Thus, E138A is considered as a TDR mutation. 2018 PloS one Result HIV E138A 6 11 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. No neutron crystal structures have been reported for the inhibitor complexes in this study; hence, hydrogen bonds for L76V complexes are described by the same criteria as for previously published wild-type complexes (Figure 3). 2018 ACS omega Result HIV L76V 118 122 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Once again, the lack of significant differences in PR active-site interactions with 4 indicates that the resistance mechanism induced by L76V relies on an alternate strategy. 2018 ACS omega Result HIV L76V 137 141 PR 51 53 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Similar effects were observed for the neutron structure of amprenavir complexed with PR mutant V32I/I47V/V82I. 2018 ACS omega Result HIV I47V;V32I;V82I 100;95;105 104;99;109 PR 85 87 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Therefore, mutation L76V does not produce major alterations in the overall structure of the PR dimer. 2018 ACS omega Result HIV L76V 20 24 PR 92 94 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. These higher Ki values imply that L76V confers resistance toward the four tested inhibitors. 2018 ACS omega Result HIV L76V 34 38 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. However, the four sequences that had the G190A mutation were collected during three of the four surveillance studies in Gondar 2003-2013 (Table 2 and Fig 2) suggesting onward transmission of this DRM over many years in Gondar. 2018 PloS one Result HIV G190A 41 46 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. In subcluster 12a, four of nine sequences carried the G190A mutation (Table 2 and Fig 2) which suggested cluster-associated transmission of this resistance mutation in Gondar. 2018 PloS one Result HIV G190A 54 59 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. Taken together, the G190A/S/E mutations were most prominent (seven of the 12 NNRTI mutations), followed by the K103N, Y181I/C and K101E substitutions (two, two and one, respectively). 2018 PloS one Result HIV G190A;G190E;G190S;K101E;K103N;Y181C;Y181I 20;20;20;130;111;118;118 29;29;29;135;116;125;125 NNRTI 77 82 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. Two had K103N, one G190S and one Y181C, all representing resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). 2018 PloS one Result HIV G190S;K103N;Y181C 19;8;33 24;13;38 NNRTI;NNRTI 71;120 107;125 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. K65R emerged in 7.6% of 184 genotyping tests. 2018 BMC infectious diseases Result HIV K65R 0 4 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. The NRTI(t)-associated mutation M184 V/I emerged in 78.4% of the subtype B sequences and in 21.6% of the non-B subtype sequences (p = 0.009). 2018 BMC infectious diseases Result HIV M184I;M184V 32;32 40;40 NRTI 4 8 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. 3A, virus replication was markedly delayed in the cultures transfected with the P122A and I124A mutants. 2018 mBio Result HIV I124A;P122A 90;80 95;85 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. 4A; P122A, data not shown). 2018 mBio Result HIV P122A 4 9 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. 5C and D), while Q176 adopted the WT conformation in the P124A mutant, despite some flexibility. 2018 mBio Result HIV P124A 57 62 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. 7E), V11I was introduced in the I124A molecular clone as well. 2018 mBio Result HIV I124A;V11I 32;5 37;9 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. 8C); the former combination was also capable of rescuing the replication competency of I124A. 2018 mBio Result HIV I124A 87 92 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. All of the viruses containing second-site changes, except for the A105T/P122A mutant, were replication competent in MT-4 cells (data not shown). 2018 mBio Result HIV A105T;P122A 66;72 71;77 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Among the P122A-containing viruses, three mutants:T107I/P122A, V36I/P122A, and A105T/P122A:did not replicate during 2 months in culture in three independent experiments. 2018 mBio Result HIV A105T;P122A;P122A;P122A;P122A;T107I;V36I 79;10;56;68;85;50;63 84;15;61;73;90;55;67 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Analysis of these data revealed broader size distributions for the P122A PR- and I124A PR- particles than for the WT PR- particles, and the size range peaked at a smaller diameter. 2018 mBio Result HIV I124A;P122A 81;67 86;72 PR;PR;PR 73;87;117 75;89;119 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Analyzing the T58S/T107I/P122A PR- revertant particles further by cryo-ET, we found that the compensatory mutations restored immature Gag lattice formation and particle size distribution to WT-like levels. 2018 mBio Result HIV P122A;T107I;T58S 25;19;14 30;24;18 Gag;PR 134;31 137;33 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. As a starting point, the highly permissive MT-4 T-cell line was transfected with WT, P122A, and I124A pNL4-3 molecular clones, and virus replication was monitored by RT assay. 2018 mBio Result HIV I124A;P122A 96;85 101;90 RT 166 168 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. As demonstrated above, the P122A and I124A mutants are unable to produce virions containing mature cone-shaped cores, thereby impeding investigation of the role of the motif in assembling the mature CA lattice in the context of virus particles. 2018 mBio Result HIV I124A;P122A 37;27 42;32 Capsid 199 201 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. As similar defects in virion morphology were observed for the two mutants, we performed cryo-ET analysis only for the I124A particles. 2018 mBio Result HIV I124A 118 123 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. As the T58A mutation also rescued the replication capacity of I124A in MT-4 cells (data not shown) and Jurkat cells. 2018 mBio Result HIV I124A;T58A 62;7 67;11 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Because the six-helix CA-SP1 bundle is the target of MI activity, these data suggest that bundle formation is not blocked by the P122A and I124A mutations, despite their marked impact on particle assembly. 2018 mBio Result HIV I124A;P122A 139;129 144;134 SP1;Capsid 25;22 28;24 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Consistent with the results of virus release assays performed with PR+ mutants, production of immature particles was impaired by the P122A and I124A mutations. 2018 mBio Result HIV I124A;P122A 143;133 148;138 PR 67 69 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. However, again, WT-like replication kinetics were consistently observed only for the triple mutant, V11I/T58A/I124A. 2018 mBio Result HIV I124A;T58A;V11I 110;105;100 115;109;104 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. However, some differences in assembly efficiency were observed; P122A CA protein assembled with kinetics that were even faster than those of the WT, whereas I124A CA assembled more slowly than the WT and, unlike the WT and P122A CA protein, did not assemble at concentrations of <6 mg/ml (data not shown). 2018 mBio Result HIV I124A;P122A;P122A 157;64;223 162;69;228 Capsid;Capsid;Capsid 70;163;229 72;165;231 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. In contrast to P122A mutant viruses, T58A significantly improved replication of the I124A mutant, with T58A/I124A showing a delay of only 4 to 6 days relative to the WT. 2018 mBio Result HIV I124A;I124A;P122A;T58A;T58A 84;108;15;37;103 89;113;20;41;107 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. In contrast, and consistent with their defects in virus assembly and release, the P122A and I124A mutants replicated with a significant delay relative to the WT in MT-4 cells and were not able to replicate in Jurkat cells. 2018 mBio Result HIV I124A;P122A 92;82 97;87 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. In contrast, P122A and I124A viral particles lacked the characteristic conical core observed with WT HIV-1 virions. 2018 mBio Result HIV I124A;P122A 23;13 28;18 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. In contrast, the subtomogram average data determined for the P122A PR- particles showed no evidence of the WT immature Gag lattice, and the CA layer was thinner and nonstriated in the cross-sectional view. 2018 mBio Result HIV P122A 61 66 Gag;Capsid;PR 119;140;67 122;142;69 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. In some cases, the I124A mutant reverted via a primary-site change (I124V or I124T). 2018 mBio Result HIV I124A;I124T;I124V 19;77;68 24;82;74 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Indeed, we observed that BVM and the two BVM analogs significantly inhibited P122A and I124A CA-SP1 processing, albeit not to the same level as observed with the WT (Fig 2E). 2018 mBio Result HIV I124A;P122A 87;77 92;82 SP1;Capsid 96;93 99;95 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Moreover, residue Q176 in the P122A mutant assumed a conformation different from that seen with CA WT. 2018 mBio Result HIV P122A 30 35 Capsid 96 98 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Overall, a combination of two mutations:V11I/T58A or T58S/T107I:was able to compensate for the original defect caused by the P122A substitution, leading to production of infectious virions. 2018 mBio Result HIV P122A;T107I;T58A;T58S;V11I 125;58;45;53;40 130;63;49;57;44 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Overall, experiments performed to select revertant viruses revealed that the combination of two mutations, V11I and T58A, completely rescues the replication defects imposed by both P122A and I124A in Jurkat cells and that a variety of other mutations are able to confer partial rescue. 2018 mBio Result HIV I124A;P122A;T58A;V11I 191;181;116;107 196;186;120;111 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Overall, the mutant structures are similar to those of the WT CA (root mean square deviation [RMSD], 0.394 A for P122A and 0.400 A for I124A), indicating that the mutations did not disrupt the overall folding of the CA protein. 2018 mBio Result HIV I124A;P122A 135;113 140;118 Capsid;Capsid 62;216 64;218 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A and I124A subtly affect formation of the CA hexagonal lattice. 2018 mBio Result HIV I124A;P122A 10;0 15;5 Capsid 47 49 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Protease-deficient P122A and I124A virions have a morphologically abnormal Gag lattice. 2018 mBio Result HIV I124A;P122A 29;19 34;24 PR;Gag 0;75 8;78 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Relative to WT viruses, the P123A and P125A mutants showed 70% and 20% infectivity, respectively, whereas P122A and I124A viruses were noninfectious. 2018 mBio Result HIV I124A;P122A;P123A;P125A 116;106;28;38 121;111;33;43 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Similarly to P122A-containing viruses, V11I alone was unable to compensate for the replication defects conferred by I124A. 2018 mBio Result HIV I124A;P122A;V11I 116;13;39 121;18;43 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Similarly, the Gag processing defects observed with the original P122A and I124A mutants were corrected in the revertants. 2018 mBio Result HIV I124A;P122A 75;65 80;70 Gag 15 18 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Specifically, the P122A and I124A mutations resulted in alterations in the PPIP motif itself and induced subtle repositioning of residues 92 to 96 in the CypA loop. 2018 mBio Result HIV I124A;P122A 28;18 33;23 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. TEM analysis of those virus particles revealed significant gaps or discontinuities in the Gag-like lattice for both mutants (I124A. 2018 mBio Result HIV I124A 125 130 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The electron micrographs demonstrated that P123A and P125A mutant particles were morphologically similar to the WT particles (data not shown). 2018 mBio Result HIV P123A;P125A 43;53 48;58 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The I124A PR- particles were of essentially the same morphotype. 2018 mBio Result HIV I124A 4 9 PR 10 12 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The loading volumes were adjusted to account for the fact that the P122A and I124A mutants release less virus than the WT. 2018 mBio Result HIV I124A;P122A 77;67 82;72 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The P122A and I124A mutants also showed an accumulation of Gag patches at the PM of virus-producing cells, suggesting a structural role for these residues early in the assembly process. 2018 mBio Result HIV I124A;P122A 14;4 19;9 Gag 59 62 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The results indicated that both the P122A and I124A CA proteins were able to assemble into tubes in vitro. 2018 mBio Result HIV I124A;P122A 46;36 51;41 Capsid 52 54 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The virus release defects exhibited by the P122A and I124A mutants were associated with impaired Gag processing, as measured by the ratio of cell-associated CA to the total amount of Pr55Gag and CA in cell lysates. 2018 mBio Result HIV I124A;P122A 53;43 58;48 Gag;Capsid;Capsid;PR 97;157;195;183 100;159;197;185 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. These data demonstrate that P122A and I124A mutants exhibit Gag processing defects not only in producer cells but also in released virions. 2018 mBio Result HIV I124A;P122A 38;28 43;33 Gag 60 63 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. These data suggest that defects in virus particle production by P122A and I124A viruses are not caused by aberrant Gag processing. 2018 mBio Result HIV I124A;P122A 74;64 79;69 Gag 115 118 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. To address the effect of the PPIP mutations on the formation of the mature CA hexamer, full-length CA proteins bearing P122A or I124A mutations were crystallized. 2018 mBio Result HIV I124A;P122A 128;119 133;124 Capsid;Capsid 75;99 77;101 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. To analyze the ability of the second-site mutations acquired during passaging to rescue the defects conferred by the P122A and I124A substitutions, we introduced these mutations into the P122A or I124A clones. 2018 mBio Result HIV I124A;I124A;P122A;P122A 127;196;117;187 132;201;122;192 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. To elucidate the interplay between the PPIP loop and the remainder of CA during virus assembly and maturation, we selected for viruses with compensatory mutations that rescue the defects imposed by P122A and I124A. 2018 mBio Result HIV I124A;P122A 208;198 213;203 Capsid 70 72 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. To elucidate the mechanism by which the identified CA-NTD mutations corrected the replication defects imposed by the P122A and I124A substitutions, we focused on the four viral revertants:T58S/T107I/P122A, V11I/T58A/P122A, T58A/I124A, and V11I/T58A/I124A:that exhibited the most improved replication kinetics in Jurkat cells. 2018 mBio Result HIV I124A;P122A;P122A;T107I;T58A;T58A;T58S;V11I;V11I;I124A;I124A;P122A;T58A 249;199;216;193;211;244;188;206;239;127;228;117;223 254;204;221;198;215;248;192;210;243;132;233;122;227 Capsid 51 53 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. To further characterize the defects in the structure of the immature Gag lattice caused by the P122A and I124A mutations, protease-deficient WT and mutant particles were visualized by cryo-ET. 2018 mBio Result HIV I124A;P122A 105;95 110;100 PR;Gag 122;69 130;72 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. To further define the role of the PPIP loop in virus assembly, we characterized PR- derivatives of the P122A and I124A molecular clones. 2018 mBio Result HIV I124A;P122A 113;103 118;108 PR 80 82 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. To investigate further the ability of the selected second-site mutations to rescue P122A- and I124A-imposed defects, we performed replication assays in the less permissive Jurkat T-cell line. 2018 mBio Result HIV I124A;P122A 94;83 99;88 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We found that T58A/P122A acquired an additional change, V11I. 2018 mBio Result HIV P122A;T58A;V11I 19;14;56 24;18;60 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We found that while mutation P123A did not affect virus production, mutations P122A, I124A, and P125A reduced virus particle production to ~40%, 25%, and 60% of WT levels, respectively. 2018 mBio Result HIV I124A;P122A;P123A;P125A 85;78;29;96 90;83;34;101 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We introduced V11I in the context of P122A and T58A/P122A and observed that, while V11I alone was not able to rescue the replication defects exhibited by P122A, the V11I/T58A/P122A triple mutant displayed WT-like replication kinetics in three independent experiments. 2018 mBio Result HIV P122A;T58A;V11I;P122A;P122A;P122A;T58A;V11I;V11I 175;170;165;37;52;154;47;14;83 180;174;169;42;57;159;51;18;87 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We observed that CA-SP1 cleavage was around four times less efficient in P122A and I124 particles than in the WT particles. 2018 mBio Result HIV P122A 73 78 SP1;Capsid 20;17 23;19 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We observed that the P123A and P125A viruses were replication competent in MT-4 and Jurkat cells. 2018 mBio Result HIV P123A;P125A 21;31 26;36 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We performed in vitro assembly reactions with WT, P122A, and I124A CA proteins and examined the assembly products by EM. 2018 mBio Result HIV I124A;P122A 61;50 66;55 Capsid 67 69 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We thus examined whether BVM and two potent BVM analogs (7m and 7r) are able to block CA-SP1 processing of the P122A and I124A mutants. 2018 mBio Result HIV I124A;P122A 121;111 126;116 SP1;Capsid 89;86 92;88 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. We verified that I124A virions lacked the conical core seen in WT particles and also lacked any other higher-order structure made of the same (mature) lattice; we infer that these particles represent maturation-defective virions at various stages of Gag processing. 2018 mBio Result HIV I124A 17 22 Gag 250 253 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. Four carried mutations towards NNRTI only (K103N and K103N/S) and one carried mutations to both NNRTI (G190S, K101E) and NRTI (M184V) No DRM toward protease inhibitors (PIs) was found. 2018 PloS one Result HIV G190S;K101E;K103N;K103N;K103S;M184V 103;110;43;53;53;127 108;115;49;60;60;132 PR;NNRTI;NNRTI;NRTI;PI 148;31;96;121;169 156;36;101;125;172 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Among all DRM20% detected in ART-initiator participants (n = 148), 137/148 (92.6%) belonged to the NNRTI class, mostly represented by the K103N/S mutations (n = 88/137, 64.2%), while 11/148 (7.4%) were NRTI mutations (Figure 1a). 2019 The Journal of antimicrobial chemotherapy Result HIV K103N;K103S 138;138 145;145 NNRTI;NRTI 99;202 104;206 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Among ART-exposed participants, only one had low-level resistance to dolutegravir (Q148R) among participants with available consensus sequence covering the integrase (n = 83). 2019 The Journal of antimicrobial chemotherapy Result HIV Q148R 83 88 IN 156 165 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Among NRTI DRMs, M184IV was the most prevalent (n = 36/104, 34.6%), followed by K65R (20/104, 19.2%) (Figure 1c). 2019 The Journal of antimicrobial chemotherapy Result HIV K65R;M184I;M184V 80;17;17 84;23;23 NRTI 6 10 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Fifteen participants had integrase DRM20% (15/83, 18.1%), including Q148R conferring low-level resistance to dolutegravir, and some accessory integrase mutations were also found: L74I/M (n = 12/15, 80.0%), E157Q (n = 1) and G163R (n = 1). 2019 The Journal of antimicrobial chemotherapy Result HIV E157Q;G163R;L74I;L74M;Q148R 206;224;179;179;68 211;229;185;185;73 IN;IN 25;142 34;151 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. K65R was detected in 18/72 (25.0%) and 2/17 (11.8%) participants who were on a tenofovir- and stavudine-based regimen, respectively. 2019 The Journal of antimicrobial chemotherapy Result HIV K65R 0 4 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Nine additional integrase DRM5% were found, mostly L74M (n = 5). 2019 The Journal of antimicrobial chemotherapy Result HIV L74M 51 55 IN 16 25 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Notably, two additional K65R mutations were detected at the 5% as compared with the 20% variant threshold (Figure 1d). 2019 The Journal of antimicrobial chemotherapy Result HIV K65R 24 28 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. The K65R mutation was found in one participant (n = 1/11, 9.1%). 2019 The Journal of antimicrobial chemotherapy Result HIV K65R 4 8 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. The main mutations found in the NRTI class were M184V (n = 4/11, 36.4%) associated with cytosine analogues and abacavir resistance, and the main TA mutation (TAM) T215S in its revertant form (n = 3/11, 27.3%). 2019 The Journal of antimicrobial chemotherapy Result HIV M184V;T215S 48;161 53;168 NRTI 32 36 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Twenty-two more NRTI DRM5% were detected, mostly represented by the TAM-2 mutations in addition to two mutations from the TAM-1 pathway (M41L and L210W). 2019 The Journal of antimicrobial chemotherapy Result HIV L210W;M41L 146;137 151;142 NRTI 16 20 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. When DRM5% were assessed, double the number of NRTI mutations were found (n = 22), mostly represented by K65R (n = 4/22, 18.2%) and the TAMs D67N and K219EQ (Figure 1b). 2019 The Journal of antimicrobial chemotherapy Result HIV D67N;K219E;K219Q;K65R 141;150;150;105 145;156;156;109 NRTI 47 51 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. While no major mutation was described for dolutegravir resistance, we found some accessory integrase mutations in 98/524 (18.7%), such as L74I/M (n = 81/98, 82.7%), T97A (n = 8/98, 8.2%) and E157Q (n = 5/98, 5.1%), and more sporadically E138D/K (n = 2), V151I (n = 1) and G163R (n = 1). 2019 The Journal of antimicrobial chemotherapy Result HIV E138D;E138K;E157Q;G163R;L74I;L74M;T97A;V151I 237;237;191;272;138;138;165;254 244;244;196;277;144;144;169;259 IN 91 100 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. 15 subtype B sequences with the V82L mutation form cluster 2 and 16 subtype B sequences with the revertant T215S form the third large cluster (Fig 5). 2018 PloS one Result HIV T215S;V82L 107;32 112;36 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. According to predictions from the Stanford HIVdb, phenotypic INSTI resistance (excluding potential low level) was identified in 0.7% (6/820) of cases (Fig 3B) due to the presence of the T66I (n = 1), the G163R or K (n = 4) or the combination of T97A and E157Q (n = 1) resulting in low level resistance to elvitegravir and raltegravir. 2018 PloS one Result HIV E157Q;G163R;T66I;T97A 254;204;186;245 259;209;190;249 INSTI 61 66 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Among the `not cluster-linked sequences carrying the K103N mutation the diversity of HIV-1 subtypes (A, B, C, G, CRF02_AG) as well as the origin of infected persons (Germany, East Europe, West Europe, Latin America, Sub Saharan Africa and not reported) was much higher. 2018 PloS one Result HIV K103N 54 59 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Around 40% of the sequences carrying the K103N mutation were found within nine different clusters (all subtype B, cluster size of 2-4 sequences per cluster) (Table 5, Fig 5). 2018 PloS one Result HIV K103N 41 46 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Cluster 1 consists of 11 subtype A sequences with the M46I mutation. 2018 PloS one Result HIV M46I 54 58 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Less frequently observed were the mutations D67N (n = 8), K65R (n = 2) and K70R (n = 2). 2018 PloS one Result HIV D67N;K65R;K70R 44;58;75 48;62;79 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. PI-mutations M46I/L and V82L that are responsible for low or intermediate resistance levels to tipranavir, nelfinavir and fosamprenavir (Fig 3B) were also frequently present (Table 4) but without identifiable tendency during the study period (Fig 3A). 2018 PloS one Result HIV M46I;M46L;V82L 13;13;24 19;19;28 PI 0 2 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Sequences that had one or more of the most frequent NRTI, NNRTI and PI resistance mutations or the polymorphic E138A (listed in Table 4) were selected for phylogenetic analysis (n = 251). 2018 PloS one Result HIV E138A 111 116 NNRTI;NRTI;PI 58;52;68 63;56;70 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Special attention was paid to the clustering of the K103N mutation in order to analyse whether the previously described increase in 2015/2016 was the result of a recent spread within one or few active transmission networks and/or within a specific transmission group. 2018 PloS one Result HIV K103N 52 57 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. The M184V, K70R and K65R mutations induce high level resistance to NRTIs in recommended first-line regimen according to EACS (9.0). 2018 PloS one Result HIV K65R;K70R;M184V 20;11;4 24;15;9 NRTI 67 72 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. The most frequently detected NNRTI-mutation was K103N. 2018 PloS one Result HIV K103N 48 53 NNRTI 29 34 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. The polymorphic NNRTI-mutation E138A not recorded in the SDRM list but associated with low level resistance to the second generation NNRTI rilpivirine according to Stanford HIVdb was found even more frequently during the whole study period (Table 4 and Fig 3B). 2018 PloS one Result HIV E138A 31 36 NNRTI;NNRTI 16;133 21;138 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. The proportion of individuals not linked to K103N-clusters was generally higher in 2015/2016 than in 2013/2014 (p = 0.01), although the sampling was more dense in 2015/2016 (n = 1,141 compared to 744 in 2013/2014). 2018 PloS one Result HIV K103N 44 49 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. The steep slope of the `total K103N between 2014 and 2016 was quite congruent in the subgroups of MSM, persons of German origin and subtype B infections (Fig 4A). 2018 PloS one Result HIV K103N 30 35 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. The thymidine analogue mutations (TAMs) M41L, K219Q and T215 revertants as well as the non-TAM M184V were among the most frequently transmitted NRTI-resistance mutations (>= 0.5%) (Table 4). 2018 PloS one Result HIV K219Q;M184V;M41L 46;95;38 51;100;44 NRTI 144 148 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Transmitted INSTI mutations according to Stanford SDRM Worksheet for INSTI were identified in a single sequence among 820 analysed cases (0.12%), namely the major primary mutation T66I resulting in high level resistance to elvitegravir and low level resistance to raltegravir. 2018 PloS one Result HIV T66I 180 184 INSTI;INSTI 12;69 17;74 30409215 Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay. As expected, the number and type of mutations with frequencies > 20% (those within Sanger sequencing-based detection level) matched the cART history of the patient, e.g., the virus from patient SG28 had mutations associated with resistance to ABC (L74I 97.6% frequency), 3TC (M184V 99.7%), and EFV (K103N 98.8%, P225H 99.5%) and had been exposed to RTV, DRV, ABC, 3TC, and EFV; while patient SG86 had a virus with resistance to FTC (M184V 98.9%) and RAL (L74M 97.9%, E92Q 86.1% and T97A 99.8%) after being treated over the years with RTV, LPV, DRV, FTC, TDF, and RAL (Additional file 1: Table S1). 2018 AIDS research and therapy Result HIV E92Q;K103N;L74I;L74M;M184V;M184V;P225H;T97A 467;299;248;455;276;433;312;482 471;305;253;460;282;439;317;486 30409215 Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay. Most of the minority mutations in viruses from both groups of naive patients were observed in the RT, e.g., M41L, E44D, A62V, K65R, D67N, D67G, V75I, L100I, K103N, K103R, V188I, M184I, L210W, K219Q, Y318F, etc., although a number of minority mutations associated with resistance to PI (L10F, V11I, M46I/L, I50V, F53L, Q58E, T74S) or INSTI (L74I/M, E92G, E138K, S147G, G163R, Q148K) were also identified. 2018 AIDS research and therapy Result HIV A62V;D67G;D67N;E138K;E44D;E92G;F53L;G163R;I50V;K103N;K103R;K219Q;K65R;L100I;L10F;L210W;L74I;L74M;M184I;M41L;M46I;M46L;Q148K;Q58E;S147G;T74S;V11I;V188I;V75I;Y318F 120;138;132;354;114;348;312;368;306;157;164;192;126;150;286;185;340;340;178;108;298;298;375;318;361;324;292;171;144;199 124;142;136;359;118;352;316;373;310;162;169;197;130;155;290;190;346;346;183;112;304;304;380;322;366;328;296;176;148;204 INSTI;PI;RT 333;282;98 338;284;100 30409215 Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay. Most of these minority drug resistance mutations were detected in the 67 cART-experienced individuals, e.g., the HIV-1 genotype of the following patients consisted of a mixture of majority and minority drug resistance mutations: patient SG79 (PR V11I 99.9%, K20I 99.9%; RT E44D 1.3%, D67N 1.1%, L100I 1.7%, M184V 84.9%, M184I 14.8%, K219Q 2.1%, INT E157Q 99.8%), patient SG86 (RT M184V 99.8%, INT L74M 97.9%, L74I 1.9%, E92Q 86.1%, E92V 7.4%, T97A 99.8%, G163R 1.1%), patient NHS49 (PR E35G 1.3%, M46L 3.1%, I50 V 2.5%, F53L 1.4%, RT M41L 99.2%, D67N 2.3%, M184V 15.4%, T215Y 99.1%) and patient NHS72 (PR M46L 1.1%, RT D67N 1.4%, K103R 99.6%, M184V 99.8%, Y188C 19.3%, INT T66I 99.8%, L74I 99.8%, T97A 98.8%, E157Q 8.7%). 2018 AIDS research and therapy Result HIV D67N;D67N;D67N;E157Q;E157Q;E35G;E44D;E92Q;E92V;F53L;G163R;I50V;K103R;K20I;K219Q;L100I;L74I;L74I;L74M;M184I;M184V;M184V;M184V;M184V;M41L;M46L;M46L;T215Y;T66I;T97A;T97A;V11I;Y188C 284;546;619;349;709;486;273;420;432;520;455;508;630;258;333;295;409;685;397;320;307;380;557;643;534;497;605;570;673;443;697;246;656 288;550;623;354;714;490;277;424;436;524;460;513;635;262;338;300;413;689;401;325;312;385;562;648;538;501;609;575;677;447;701;250;661 PR;PR;PR;RT;RT;RT;RT 243;483;602;270;377;531;616 245;485;604;272;379;533;618 30409215 Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay. The most prevalent primary minority drug resistance mutations observed in both cohorts of patients were the PIs M46I/L (in 3 and 9 SG and NHS individuals, respectively) and I50 V (2 and 5); the NRTIs D67N (23 and 20), K65R (0 and 9), L74I (2 and 0), M184V/I (6 and 0) and K219Q (9 and 10); and the NNRTI L100I (6 and 3). 2018 AIDS research and therapy Result HIV D67N;I50V;K219Q;K65R;L100I;L74I;M184I;M184V;M46I;M46L 200;173;272;218;304;234;250;250;112;112 204;178;277;222;309;238;257;257;118;118 NNRTI;NRTI;PI 298;194;108 303;199;111 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. Mutation K65R, associated with resistance to TDF, was found in four patients at baseline; however, after switching to second-line ART, K65R mutations were not detected. 2018 BMC infectious diseases Result HIV K65R;K65R 9;135 13;139 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. No major resistance to PIs was detected in our study; minor drug resistance to the PIs, A71V/T and L10I, were detected during second-line therapy. 2018 BMC infectious diseases Result HIV A71T;A71V;L10I 88;88;99 94;94;103 PI;PI 23;83 26;86 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. TAM (M41 L, K70R, L210 W, and T215F) and D67N mutations, associated with resistance to TDF, were detected during second-line ART. 2018 BMC infectious diseases Result HIV D67N;K70R;L210W;M41L;T215F 41;12;18;5;30 45;16;24;10;35 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. The M184 V/I mutation was detected in five patients, one patient, two patients, and one patient at the 6, 12, 18, and 48 month timepoints, respectively. 2018 BMC infectious diseases Result HIV M184I;M184V 4;4 12;12 30477526 Long-term virological outcome in children receiving first-line antiretroviral therapy. A retrospective DRM testing showed that only 6.4% (5/78) of the children had K103N as the major DRM at baseline (pre-ART). 2018 AIDS research and therapy Result HIV K103N 77 82 30477526 Long-term virological outcome in children receiving first-line antiretroviral therapy. DRM results were available for 3 of these children at 12th month and they had either M184V or M184I mutation in addition to K103N at this time point. 2018 AIDS research and therapy Result HIV K103N;M184I;M184V 124;94;85 129;99;90 30477526 Long-term virological outcome in children receiving first-line antiretroviral therapy. K103N (48%), Y181C (37%), G190A/S (25%), Y188C/L (10%), V106M/A (8%), K65R (8%) and L100I (4%) were the major NNRTI DRMs observed in these 52 children. 2018 AIDS research and therapy Result HIV G190A;G190S;K65R;L100I;V106A;V106M;Y181C;Y188C;Y188L;K103N 26;26;70;84;56;56;13;41;41;0 33;33;74;89;63;63;18;48;48;5 NNRTI 110 115 30477526 Long-term virological outcome in children receiving first-line antiretroviral therapy. M184V/I was present in 79% (41/52) of the children, and 27% (14/52) had Thymidine analog mutations (TAMs). 2018 AIDS research and therapy Result HIV M184I;M184V 0;0 7;7 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. Genotypic testing (GenoSure MG) for the HIV strain isolated from this patient showed notable RT mutations of L74V, L100I, M184V, and K103N, none of which are known to confer resistance to TDF, although M184V confers high-level resistance to FTC. 2018 The lancet. HIV Result HIV K103N;L100I;L74V;M184V;M184V 134;116;110;123;203 139;121;114;128;208 RT 94 96 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. SGS detected minor resistance mutations in the PR gene that were not reported in the standard genotype (D30N (3.6%), G73S (1.8%) and G48E (5.5%). 2018 The lancet. HIV Result HIV D30N;G48E;G73S 104;133;117 109;137;121 PR 47 49 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. SGS was consistent with the standard genotype in detecting RT mutations: specifically L74V, L100I, M184V, and K103N were detected, but K65R and K70E were not. 2018 The lancet. HIV Result HIV K103N;K65R;K70E;L100I;L74V;M184V 110;135;144;92;86;99 115;139;148;97;90;104 RT 59 61 30513108 Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial. One participant had predicted intermediate-level (mutations T97A+R263K) and two predicted high-level (N155H, T97A+Y143R/C) raltegravir resistance mutations (0.6% of those randomised, accounting for missing genotypes using probability weights). 2018 PLoS medicine Result HIV N155H;R263K;T97A;T97A;Y143C;Y143R 102;65;60;109;114;114 107;70;64;113;121;121 30513108 Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial. Similar late differences were observed for BMI in adolescents/adults (data not shown), fat mass (S11A and S11B Fig), and muscle mass (S11C and S11D Fig). 2018 PLoS medicine Result HIV S11A;S11C;S11D 97;134;143 102;139;147 30513108 Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial. The NRTI mutation K219E/Q (p = 0.004) and the NNRTI mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in raltegravir-intensified ART, with no evidence of differences for other mutations (p > 0.1, S8 Fig). 2018 PLoS medicine Result HIV K101E;K101P;K219E;K219Q;P225H 62;62;18;18;85 69;69;25;25;90 NNRTI;NRTI 46;4 51;8 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. A similar repacking was also observed in the I50V-DRV structure, where increased packing against I47 in both chains compensated lost vdW interactions at residue 50. 2019 ACS infectious diseases Result HIV I50V 45 49 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. A time-course gel shift assay confirmed the catalytic activity of I50V single mutant, and the rescued activity of I50V/A71V variant in cleaving purified Gag polyprotein [Figure S1]. 2019 ACS infectious diseases Result HIV A71V;I50V;I50V 119;66;114 123;70;118 Gag 153 156 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. A71V, a compensatory mutation that is far from the active site and almost always observed with I50V, restores the functionality to WT level (Km = 73 +- 9 muM), as previously reported. 2019 ACS infectious diseases Result HIV I50V;A71V 95;0 99;4 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Against I84V and I50V mutations, which are located directly at the pocket where P1' moiety binds, UMass1 experienced a similar reduction in potency as DRV [Table 1]. 2019 ACS infectious diseases Result HIV I50V;I84V 17;8 21;12 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Against I84V mutation, enhanced packing at the P1' moiety of UMass6 resulted in overall better interactions and potency. 2019 ACS infectious diseases Result HIV I84V 8 12 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. All three protease variants had a single mutation that altered the shape of the hydrophobic S1/S1' pocket of HIV-1 protease: I50V, V82I and I84V. 2019 ACS infectious diseases Result HIV I50V;I84V;V82I 125;140;131 129;144;135 PR;PR 10;115 18;123 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Although both I84V and I50V mutations cause the same reduction in side chain size, these two mutations had the opposite effect on the change in potency of UMass6 compared to DRV and UMass1. 2019 ACS infectious diseases Result HIV I50V;I84V 23;14 27;18 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Although the position of most of the flap residues were altered in the UMass6-I50V structure relative to WT complex, the typical hydrogen bond distances were not significantly perturbed [Figure S3, Table S4]. 2019 ACS infectious diseases Result HIV I50V 78 82 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. As in the V82I variant, the binding mode and hydrogen bonds of DRV were not altered in I84V and I50V structures [Figure 2b]. 2019 ACS infectious diseases Result HIV I50V;I84V;V82I 96;87;10 100;91;14 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Comparison of the variant structures to their corresponding WT structures shows the discrepancy between the I50V-UMass6 and all the other 11 structures [Figure S4]. 2019 ACS infectious diseases Result HIV I50V 108 112 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Contrary to the case of I84V mutation, UMass6 bound to the I50V variant with the lowest potency. 2019 ACS infectious diseases Result HIV I50V;I84V 59;24 63;28 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. However, there was no compensation at residue 47 interactions in either chain, due to the different conformer of I47, which resulted in a greater overall loss in vdW interactions, in agreement with the greatest potency loss observed for UMass6 against I50V mutation. 2019 ACS infectious diseases Result HIV I50V 252 256 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. However, this alternate compensation was more distributed and subtle, which may underlie the slightly worse Ki of UMass1 compared to DRV against I50V protease. 2019 ACS infectious diseases Result HIV I50V 145 149 PR 150 158 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. However, van der Waals (vdW) interactions with residues 84 and 84' decreased due to I84V mutation, which was in part compensated by increased packing against I47 and V82' [Table 2]. 2019 ACS infectious diseases Result HIV I84V 84 88 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. I50V Mutation Induces Conformational Changes in Both UMass6 and Protease Flaps. 2019 ACS infectious diseases Result HIV I50V 0 4 PR 64 72 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. In addition to this inhibitor's unique binding conformation, the flaps in I50V protease underwent rather large-scale changes: In chain A, I47 assumed a rare rotamer to maintain interaction with the sterically smaller I50V [Figure S2]. 2019 ACS infectious diseases Result HIV I50V;I50V 74;217 78;221 PR 79 87 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. In agreement with the maintained potency against V82I variant, the hydrogen bonding and packing of DRV at the active site was conserved in the V82I crystal structure [Figure 2b and Table 2]. 2019 ACS infectious diseases Result HIV V82I;V82I 49;143 53;147 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. In the I84V variant, residues V32' and L23' in chain B underwent a side chain conformer change relative to WT protease [Figure S2]. 2019 ACS infectious diseases Result HIV I84V 7 11 PR 110 118 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. In the V82I structure, while DRV did not gain significant interactions compared to WT complex, UMass1 and UMass6 gained approximately 2 kcal/mol in vdW energy as their P1' moieties directly interact, but not clash, with the sterically larger side chain. 2019 ACS infectious diseases Result HIV V82I 7 11 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. In UMass6, the methyl groups on both branches of the P1' moiety help UMass6 to better accommodate the steric space provided by the I84V mutation, leading to a 2-fold improvement in Ki compared to the other two inhibitors. 2019 ACS infectious diseases Result HIV I84V 131 135 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Interestingly, the resulting vdW losses of UMass6 with residue 50 due to the I50V mutation were completely asymmetric, with a loss similar to DRV and UMass1 in chain A but almost no loss in chain B [Table 2]. 2019 ACS infectious diseases Result HIV I50V 77 81 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Intriguingly, the I84V and I50V complexes fell on separate but parallel lines, together defining a set of 3 roughly parallel lines on the PC2-PC3 plane. 2019 ACS infectious diseases Result HIV I50V;I84V 27;18 31;22 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Mapping the distance-differences onto the 3D structure revealed that the structural changes due to I50V in the UMass6-bound protease propagated throughout the protein structure [Figure 4]. 2019 ACS infectious diseases Result HIV I50V 99 103 PR 124 132 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Significantly, structures containing the I84V primary resistance mutation of all 3 inhibitors clustered away from the remaining structures. 2019 ACS infectious diseases Result HIV I84V 41 45 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The additional methyl group in UMass1 is oriented away from the steric space provided by the I84V mutation but still makes additional contacts with P81 and V82. 2019 ACS infectious diseases Result HIV I84V 93 97 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The enzymatic activity of WT HIV-1 protease and chosen variants (I84V, V82I and I50V) were tested using a natural substrate sequence (MA/CA) [Table S1]. 2019 ACS infectious diseases Result HIV I50V;I84V;V82I 80;65;71 84;69;75 PR;Matrix;Capsid 35;134;137 43;136;139 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The I50V mutation was more deleterious with Ki values increasing by two orders of magnitude relative to WT protease. 2019 ACS infectious diseases Result HIV I50V 4 8 PR 107 115 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The I84V mutation caused a reduction in potency, with the Ki increasing to around 25 pM for DRV and UMass1, and approximately half of that for UMass6. 2019 ACS infectious diseases Result HIV I84V 4 8 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The primary resistance mutation I50V is known to reduce catalytic activity, and while I50V is still catalytically active, the Km value is beyond the limit of detection for this assay. 2019 ACS infectious diseases Result HIV I50V;I50V 32;86 36;90 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The structural rearrangements of the protease in the I50V-UMass6 structure were quantified and visualized by distance-difference matrices [Figure S4]. 2019 ACS infectious diseases Result HIV I50V 53 57 PR 37 45 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The UMass1-I84V structure displayed the same phenomenon of asymmetric inhibitor repacking as with DRV [Table 2]. 2019 ACS infectious diseases Result HIV I84V 11 15 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The V82I mutation did not confer any measurable resistance for the inhibitors, with the Ki staying below 5 pM. 2019 ACS infectious diseases Result HIV V82I 4 8 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. These 3 lines were ordered according to experimentally measured potency, with the I84V complexes nearer to the high affinity line, followed by the I50V complexes. 2019 ACS infectious diseases Result HIV I50V;I84V 147;82 151;86 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. This asymmetric compensation indicates subtle alterations in the overall packing of the inhibitor at the active site, which reduced the effect of I84V mutation on potency. 2019 ACS infectious diseases Result HIV I84V 146 150 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Thus, although the Ki values are below the limit of detection, structural analysis suggests that V82I mutation might confer hyper-susceptibility to UMass1 and UMass6 inhibitors; thus unlike with DRV, the V82I mutation is not likely to be selected under the pressure of these inhibitors. 2019 ACS infectious diseases Result HIV V82I;V82I 97;204 101;208 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Thus, the crystal structures indicate that although the potency loss against I50V is similar for DRV and UMass1, the underlying structural changes and repacking at the active site are distinct. 2019 ACS infectious diseases Result HIV I50V 77 81 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Thus, the inhibitor with the largest P1' moiety performed 2-fold better than the other inhibitors against I84V variant. 2019 ACS infectious diseases Result HIV I84V 106 110 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Thus, the structures explain why the V82I single mutation did not confer resistance to DRV, and in agreement with previous studies reveal the rearrangements in vdW packing around DRV underlying susceptibility to I50V. 2019 ACS infectious diseases Result HIV I50V;V82I 212;37 216;41 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Unexpectedly, the P1' moiety of UMass6 in I50V protease structure adopted a completely different conformation compared to the other 11 structures [Figure 3]. 2019 ACS infectious diseases Result HIV I50V 42 46 PR 47 55 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Weakening of inhibitor hydrogen bonding with D29-D30 has been reported to be coupled with increased flap flexibility in drug resistance due to I50V. 2019 ACS infectious diseases Result HIV I50V 143 147 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. When UMass1 bound I50V, there was a reduction in vdW interactions at residue 50 and 50' as seen for DRV, but no compensation at residue 47. 2019 ACS infectious diseases Result HIV I50V 18 22 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. WT NL4-3 HIV-1 protease had a Michaelis-Menten constant, Km, of 71 +- 7 muM for cleaving this substrate, which was similar to that of I84V and V82I variants (66 +- 4 and 62 +- 4 muM, respectively). 2019 ACS infectious diseases Result HIV I84V;V82I 134;143 138;147 PR 15 23 30557314 The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. Finally, the I559P mutation was introduced to stabilise the gp41 trimer thus generating CAP256 SU gp140-FL-IP (afterwards referred to as CAP256 gp140). 2018 PloS one Result HIV I559P 13 18 gp140;gp140;gp41;Capsid;Capsid 98;144;60;88;137 103;149;64;90;139 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. One volunteer had dual-class NRTI (M184V) and NNRTI (Y181C) resistance mutations. 2018 PloS one Result HIV M184V;Y181C 35;53 40;58 NNRTI;NRTI 46;29 51;33 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. The most prevalent TDR mutation was the K103N mutation (n = 5). 2018 PloS one Result HIV K103N 40 45 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. The most common NNRTIs mutations were K103 N/R/S, V179D/E, and G190A, with DR rates of 21.59, 20.45, and 18.18%, respectively. 2019 Virology journal Result HIV G190A;K103N;K103R;V179D;V179E 63;38;38;50;50 68;48;48;57;57 NNRTI 16 22 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. The most common NRTIs mutations were M184 V/I, T69S, and T215Y/I, with DR rates of 37.7, 16.39, and 14.75%, respectively. 2019 Virology journal Result HIV M184I;M184V;T215I;T215Y;T69S 37;37;57;57;47 45;45;64;64;51 NRTI 16 21 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. The mutation M184 V/I principally appeared in the first antiviral treatment failure, whereas the T215Y/I mutation was mainly associated with the second and third occasions. 2019 Virology journal Result HIV M184I;M184V;T215I;T215Y 13;13;97;97 21;21;104;104 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. The PI mutations most commonly found were L10 V/F/I, A71V, and I54V, with DR rates of 6.82, 4.55, and 4.55%, respectively. 2019 Virology journal Result HIV A71V;I54V;L10V 53;63;42 57;67;51 PI 4 6 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. As noted above, 13c2 can inhibit single (L100I, K103N, Y181C, Y188L, E138K) and double (F227+V106A) mutated HIV-RT variants (see Figure S3 for the location of these mutations). 2019 Journal of medicinal chemistry Result HIV V106A;E138K;K103N;L100I;Y181C;Y188L 93;69;48;41;55;62 98;74;53;46;60;67 RT 112 114 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Especially, 13c2 and 13c4 exhibited higher potency against K103N mutant strain than WT HIV-1 strain (RF = 0.6 and 0.5, respectively), with EC50 values of 0.9 and 1.2 nM, about 2.7- and 3.6-fold lower than that of ETV (EC50 = 3.3 nM). 2019 Journal of medicinal chemistry Result HIV K103N 59 64 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Five mutations (L100I, Y181C, Y188L, F227L, and V106) are located in the hydrophobic pocket that accommodates the benzonitrile and benzamide moieties of the ligand. 2019 Journal of medicinal chemistry Result HIV F227L;L100I;Y181C;Y188L 37;16;23;30 42;21;28;35 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. For F227L+V106A, 13c3 (EC50 = 7.2 nM) showed the highest potency and was 2.7-fold more potent than ETV (EC50 = 19.7 nM). 2019 Journal of medicinal chemistry Result HIV F227L;V106A 4;10 9;15 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. In the case of L100I, Y181C, Y188L, and E138K, 13c2, 13c3, and 13c4 provided single-digit nanomolar activities (EC50 = 0.9-8.4 nM), being superior to that of ETV. 2019 Journal of medicinal chemistry Result HIV E138K;L100I;Y181C;Y188L 40;15;22;29 45;20;27;34 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Moreover, 13a1, 13c1, 13c2, and 13c4 also inhibited F227L+V106A (EC50 = 13.7, 12.7, 19.0, and 10.5 nM) to a greater extent than ETV. 2019 Journal of medicinal chemistry Result HIV F227L;V106A 52;58 57;63 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Specifically, 13d1 inhibited the two most prevalent single mutations K103N and E138K with much lower activity (EC50 = 11.0 and 42.3 nM) and higher relative factor (RF) values (10 and 38.4) in comparison to ETV (EC50 = 3.3 and 9.7 nM, RF = 0.6 and 1.6) (Table 5). 2019 Journal of medicinal chemistry Result HIV E138K;K103N 79;69 84;74 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Subsequently, the efficacy of the compounds with potent activities toward WT and RES056 HIV-1 (13a1,2, 13c1-4, 13d1, and 13f1) were evaluated in MT-4 cells against mutant HIV-1 strains harboring single amino acid mutations L100I, K103N, Y181C, Y188L, E138K and double mutation F227L+V106A in the RT (Table 4 and Table 5). 2019 Journal of medicinal chemistry Result HIV E138K;F227L;K103N;L100I;V106A;Y181C;Y188L 251;277;230;223;283;237;244 256;282;235;228;288;242;249 RT 296 298 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. The target compounds 8a1-5, 8b1-5, 8c1-5, 8d1-5, and 8e1-5 were evaluated against wild-type (WT) HIV-1 (NL4-3) replication in TZM-bl cell lines, and compounds 13a1-6, 13b1-5, 13c1-6, 13d1-6, 13e1-6, and 13f1-5 were evaluated against WT HIV-1 (IIIB), NNRTI-resistant strain K103N+Y181C (RES056), and a HIV-2 strain (ROD) in the MT4 cell line. 2019 Journal of medicinal chemistry Result HIV K103N;Y181C 273;279 278;284 NNRTI 250 255 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. This is supported by the existence of crystallographic complexes of 25a (a ligand similar to K-5a2) with the double mutant F227+V106A (PDB code 6DUF) and with the single mutant Y181I (PDB code 6DUH) of HIV-RT.13 Finally, the K103N mutation (Figure S3) is expected to be compatible with binding of 13c2 since local protein-ligand interactions only involve the backbone amide group of residue 103. 2019 Journal of medicinal chemistry Result HIV V106A;K103N;Y181I 128;225;177 133;230;182 RT 206 208 30640198 High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014. One child had a major M46I PI mutation, which causes low level of resistance to all PIs except darunavir and tipranavir, and another had the I50L major PI mutation, which causes high level resistance to atazanavir (Table 1). 2019 The Pediatric infectious disease journal Result HIV I50L;M46I 141;22 145;26 PI;PI;PI 27;84;152 29;87;154 30640198 High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014. The most frequent mutations observed were K103N/S (48.0%), M184V (37.5%), G190A/S/E/Q/R (15.1%), and Y181C/G/V (13.8%) (Table 1). 2019 The Pediatric infectious disease journal Result HIV G190A;G190E;G190Q;G190R;G190S;K103N;K103S;M184V;Y181C;Y181G;Y181V 74;74;74;74;74;42;42;59;101;101;101 87;87;87;87;87;49;49;64;110;110;110 30640198 High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014. The other eight children had accessory PI mutations (L10F, L33F, K43T, and Q58E). 2019 The Pediatric infectious disease journal Result HIV K43T;L10F;L33F;Q58E 65;53;59;75 69;57;63;79 PI 39 41 30640198 High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014. Twenty-nine (9.5%) of the children had additional NNRTI mutations (A98G, E138A/G/K/Q, H221Y, and M230L) that confer resistance to second generation NNRTI drugs etravirine and rilpivirine. 2019 The Pediatric infectious disease journal Result HIV A98G;E138A;E138G;E138K;E138Q;H221Y;M230L 67;73;73;73;73;86;97 71;84;84;84;84;91;102 NNRTI;NNRTI 50;148 55;153 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. A Kaplan-Meier analysis could be performed for 18 TDRMs (K20T, L23I, K43T, M46I/L/V, I54V, M41L, L74I, M184V, L210W, K219R, T215A/C/D/N/S and T215Y). 2019 PloS one Result HIV I54V;K20T;K219R;K43T;L210W;L23I;L74I;M184V;M41L;M46I;M46L;M46V;T215A;T215C;T215D;T215N;T215S;T215Y 85;57;117;69;110;63;97;103;91;75;75;75;124;124;124;124;124;142 89;61;122;73;115;67;101;108;95;83;83;83;137;137;137;137;137;147 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. At NRTI position T215, the mean survival time varied with the specific substitution: T215D and T215S persisted for 4.7 (95% CI 4.4-5.1) and 4.2 (95% CI 3.5-5.1) years, respectively, while T215A and T215N persisted only for 1.6 (95% CI 1.1-2.2) and 1.0 (95% CI 1.0-1.0) years, respectively. 2019 PloS one Result HIV T215A;T215D;T215N;T215S 188;85;198;95 193;90;203;100 NRTI 3 7 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. For a number of TDRMs, no loss could be observed during the observation period (S1 Table) and, according to their maximal duration of observation, the following TDRMs seem to survive for lengthy periods in the absence of ART: the NRTI resistance mutations D67N (5.9 years), K70R (6.9 years), F77L (10.2 years), T215E (5.9 years) and K219Q (5.9 years), the NNRTI resistance mutations A98G (6.5 years) and Y188L (5.9 years) as well as the PI mutations I54L (5.9 years) and L90M (8.4 years) (S1 Table). 2019 PloS one Result HIV A98G;D67N;F77L;I54L;K219Q;K70R;L90M;T215E;Y188L 383;256;292;450;333;274;471;311;404 387;260;296;454;338;278;475;316;409 NNRTI;NRTI;PI 356;230;437 361;234;439 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. Mutations E138A/G/K/R were found in 99 of 186 viruses (52.9%) showing RPV resistance, which account for 40% of all NNRTI-resistant viruses. 2019 PloS one Result HIV E138A;E138G;E138K;E138R 10;10;10;10 21;21;21;21 NNRTI 115 120 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. Similarly, the NRTI resistance mutation M41L (6.4 years, 95% CI 6.0-6.7) and the NNRTI resistance mutation K103N (5.3 years, 95% CI 4.2-6.5) persisted for a long period. 2019 PloS one Result HIV K103N;M41L 107;40 112;44 NNRTI;NRTI 81;15 86;19 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The most common TDRMs found in baseline samples were the T215 revertants, followed by E138A/G/K/Q/R, K103NS, V179DE and M41L (S1 Table). 2019 PloS one Result HIV E138A;E138G;E138K;E138Q;E138R;K103N;K103S;M41L;V179D;V179E 86;86;86;86;86;101;101;120;109;109 99;99;99;99;99;107;107;124;115;115 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The NNRTI mutations at position E138 (E138A/G/K) had the longest mean Kaplan-Meier estimates (8.0 years, 95% CI 5.8-10.2 / 7.9 years, 95% CI 5.4-10.3 / 6.7 years, 95% CI 6.7-6.7) compared to all other TDRMs observed in this study cohort. 2019 PloS one Result HIV E138A;E138G;E138K 38;38;38 47;47;47 NNRTI 4 9 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The presence of three or more TDRMs was mainly due to the accumulation of Thymidine-Analogue-Mutations (TAMs: M41L, D67N, K70R, L210W, T215F/Y, T215 revertants and K219E/Q), which usually occur in mutation patterns. 2019 PloS one Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 116;164;164;122;128;110;135;135 120;171;171;126;133;114;142;142 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The shortest mean survival time of 1.0 year was determined for the PI resistance mutation K20T and the NRTI resistance mutation T215N (K20T 95% CI 0.6-1.4, T215N 95% CI 1.1-2.2). 2019 PloS one Result HIV K20T;K20T;T215N;T215N 90;135;128;156 94;140;133;161 NRTI;PI 103;67 107;69 30714528 Molecular Antiretroviral Resistance Markers of Human Immunodeficiency Virus-1 of CRF01_AE Subtype in Bali, Indonesia. The result shows that molecular marker mutations, which were found in more than 50% of treatment failure patients, were M184V (100%), T215A/Y/F (88.2%), D67N/G (76.5%), and M41L (58.8%). 2018 Current HIV research Result HIV D67G;D67N;M184V;M41L;T215A;T215F;T215Y 153;153;120;173;134;134;134 159;159;125;177;143;143;143 30732150 Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana. In the ART-experienced patient, 3 major drug resistance mutations (M184V, K65R, and Y115F) were found in both the PBMC and plasma sequences. 2019 Medicine Result HIV K65R;M184V;Y115F 74;67;84 78;72;89 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. A K169E mutation within CAP256 SU Env leads to the loss of binding of the native-like Env trimer-specific MAbs PG16 and CAP256 VRC26_08. 2019 Journal of virology Result HIV K169E 2 7 Env;Env;Capsid;Capsid 34;86;24;120 37;89;26;122 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. Selection of recombinant MVA, which expressed both the enhanced green fluorescent protein (eGFP) marker gene and the vaccinia virus K1L host range gene, was performed in RK13 cells. 2019 Journal of virology Result HIV K1L 132 135 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. To generate the recombinant MVA vaccines, gp150 was targeted between the transcriptionally convergent open reading frames of the essential I8R and G1L genes of either wild-type (WT) MVA or MVA-GagM. 2019 Journal of virology Result HIV I8R 139 142 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. When sera were tested against CAP256 SU K169E pseudovirions, no differences were observed compared to CAP256 SU (Table 4). 2019 Journal of virology Result HIV K169E 40 45 Capsid;Capsid 30;102 32;104 30788976 Synthesis and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors. Selected derivatives were also tested against clinically relevant K103N and Y181C HIV RT mutants (Table 1). 2019 Antiviral chemistry & chemotherapy Result HIV K103N;Y181C 66;76 71;81 RT 86 88 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. 4a, exposure to each of the RN18 analogs resulted in the rapid selection of isoleucine for valine at position 142 in Vif. 2019 mBio Result HIV V142I 76 113 Vif 117 120 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. For comparison, the IC50 values for the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) efavirenz was <1 nM for the wild-type, RN18 analog-resistant (RAR), and V142I variants. 2019 mBio Result HIV V142I 171 176 NNRTI;NNRTI;RT 40;92;77 75;97;79 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. For example, representative results showed that wild-type V142 (codon GTA) transitioned to V142I (codon ATA) in the presence of increasing amounts of IMC15 during long-term passage. 2019 mBio Result HIV V142I 91 96 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. In addition to the antagonist-resistant clone, a Vif V142I point mutant virus was included in the analysis. 2019 mBio Result HIV V142I 53 58 Vif 49 52 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. In contrast, The V142I mutation did not affect the IC50 for RN18, which was ~5.5 muM for both the wild type and the V142I variants. 2019 mBio Result HIV V142I;V142I 17;116 22;121 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Modeling with the V142I Vif mutant complex also indicated little change in the expected binding mode of RN18. 2019 mBio Result HIV V142I 18 23 Vif 24 27 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. No change in contacts was expected between V142 and the V142I mutation. 2019 mBio Result HIV V142I 56 61 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. The IC50 values for wild-type and V142I (IMC15-resistant) viruses were 2.6 muM and >25 muM, respectively. 2019 mBio Result HIV V142I 34 39 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. The V142I Vif and C9007A and Vpr null changes emerged early and were maintained throughout the culture period. 2019 mBio Result HIV C9007A;V142I 18;4 24;9 Vif;Vpr 10;29 13;32 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. The Van der Waals contacts observed between RN18 and EloC in the wt Vif complex are maintained with the V142I mutant complex, with only a slight change in orientation of the anisole ring in RN18 observed. 2019 mBio Result HIV V142I 104 109 Vif 68 71 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. The Vif V142I point mutant was modestly more fit than the wild-type virus in H9 cells. 2019 mBio Result HIV V142I 8 13 Vif 4 7 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. To understand how the V142I mutation would affect binding of IMC15 to Vif, the mutation was generated using the Prime module of Schrodinger and IMC15 was again docked to the protein using a 25-cubic-A grid centered on the coordinates x = 25.19, y = -14.1, and z = -96.93. 2019 mBio Result HIV V142I 22 27 Vif 70 73 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Treatment with each of the inhibitors resulted in the selection for this mutation, although with delayed kinetics relative to the V142I substitution in Vif. 2019 mBio Result HIV V142I 130 135 Vif 152 155 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Conversely, the S57R substitution in Tat-C increased cytokine expression levels. 2019 Scientific reports Result HIV S57R 16 20 Tat 37 40 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Effect of R57S substitution on the cellular uptake of Tat CPP. 2019 Scientific reports Result HIV R57S 10 14 Tat 54 57 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Exposure of TZM-bl cells to Tat-B-WT produced by HeLa cells transfected with expression constructs led to a robust degree of transcellular transactivation, while Tat-B-W11A led to a ~60% reduction in the level of luciferase induction compared with media containing Tat-B-WT. 2019 Scientific reports Result HIV W11A 168 172 Tat;Tat;Tat 28;162;265 31;165;268 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. However, neither the R57S substitution in Tat-B* nor the S57R substitution in Tat-C affected the intracellular levels of the respective Tat proteins when Tat was introduced directly via transfection. 2019 Scientific reports Result HIV R57S;S57R 21;57 25;61 Tat;Tat;Tat;Tat 42;78;136;154 45;81;139;157 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. In order to ensure equivalent detection of all Tat proteins, we introduced mutations in Tat-B expression constructs to create amino acid substitutions R7N and K12N of both the wild type and R57S variants. 2019 Scientific reports Result HIV K12N;R57S;R7N 159;190;151 163;194;154 Tat;Tat 47;88 50;91 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Next, we tested the effect of the R57S polymorphism on the cellular uptake of full-length Tat proteins. 2019 Scientific reports Result HIV R57S 34 38 Tat 90 93 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Processes of neurons (dendrites and axons) exposed to Tat-R57-(Tat-B* and Tat-C S57R)-treated microglial supernatants were shorter and thinner than those treated with Tat S57 (see red arrowheads in TatB WT neurotubulin panels in. 2019 Scientific reports Result HIV S57R 80 84 Tat;Tat;Tat;Tat 54;63;74;167 57;66;77;170 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. S2a) suggesting that W11A substitution does not affect transactivation when it is produced within the cell. 2019 Scientific reports Result HIV W11A 21 25 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Tat-B-WT and Tat-B-W11A yielded similar levels of luciferase output upon direct transfection into the reporter cells. 2019 Scientific reports Result HIV W11A 19 23 Tat;Tat 0;13 3;16 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Tat-B* yielded higher levels of inflammatory cytokine gene transcripts IL-6, IL-8, IL-1beta and CXCL1 than Tat-B*-R57S. 2019 Scientific reports Result HIV R57S 114 118 Tat;Tat 0;107 3;110 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. The Tat-B variant, optimized for binding to anti-Tat-C antibodies with the R7N and K12N mutations, is termed Tat-B* in our studies. 2019 Scientific reports Result HIV K12N;R7N 83;75 87;78 Tat;Tat;Tat 4;49;109 7;52;112 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Therefore, alanine substitutions were separately introduced at each of the motifs, Tat-B-W11A and Tat-B-49AAA51, and the resulting mutant Tat proteins were tested in our assay. 2019 Scientific reports Result HIV W11A 89 93 Tat;Tat;Tat 83;98;138 86;101;141 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Therefore, only Tat-B-W11A was useful for testing the impact of perturbing Tat secretion on transcellular transactivation. 2019 Scientific reports Result HIV W11A 22 26 Tat;Tat 16;75 19;78 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Therefore, we chose to investigate the effect of the HIV-1C-specific Tat R57S polymorphism on CPP uptake. 2019 Scientific reports Result HIV R57S 73 77 Tat 69 72 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. They also displayed a more beaded appearance, indicating neuronal damage, while Tat-B*-R57S and Tat-C-treated neurons displayed thicker and longer dendrites with fewer beaded dendrites (see white arrowheads in Control neurotubulin panels in. 2019 Scientific reports Result HIV R57S 87 91 Tat;Tat 80;96 83;99 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. We directly transfected TZM-bl reporter cells with Tat expression constructs with C-terminal myc tags - Tat-B* and Tat-B* R57S (HIV-1ADA) variant, Tat-C and Tat-C S57R (HIV-1BL43) variant. 2019 Scientific reports Result HIV R57S;S57R 122;163 126;167 Tat;Tat;Tat;Tat;Tat 51;104;115;147;157 54;107;118;150;160 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. When we measured TNFalpha protein levels in the supernatants of Tat-treated microglia (Luminex cytokine detection assay) we detected robust levels of TNFalpha only in the cases of Tat-B* (19.2 ng/ml) and Tat-C S57R (19.5 ng/ml) samples, compared with their Tat-S57 counterparts - where TNFalpha was undetectable. 2019 Scientific reports Result HIV S57R 210 214 Tat;Tat;Tat;Tat 64;180;204;257 67;183;207;260 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. While the R57S substitution in Tat-B* consistently decreased transactivation by a factor of 2 or 3 (~50 to 75%), S57R substitution in Tat-C increased the reporter signal by a factor of 2 (~50%). 2019 Scientific reports Result HIV R57S;S57R 10;113 14;117 Tat;Tat 31;134 34;137 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. 1C), and three hydrogen bonds in the DAT-Tat interface were eliminated by triple mutation of Y88F/K92M/H547A on hDAT. 2019 Scientific reports Result HIV H547A;K92M;Y88F 103;98;93 108;102;97 Tat 41 44 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. 2), the inhibitory effects of Tat on DAT function in WT and Y88F/H547A were presented as % of Tat-mediated [3H]DA uptake relative to their respective controls (in the absence of Tat). 2019 Scientific reports Result HIV H547A;Y88F 65;60 70;64 Tat;Tat;Tat 30;94;178 33;97;181 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. 2A, compared to WT hDAT (12.52 +- 0.68 pmol/min/105 cells), the Vmax values were increased by 92% in Y88F/H547A (24.06 +- 4.32 pmol/min/105 cells, t(7) = 2.33, p < 0.05) and dramatically decreased in Y88F/H547A/K92M (0.5 +- 0.31 pmol/min/105 cells, t(6) = 16.2, p < 0.001), respectively. 2019 Scientific reports Result HIV H547A;K92M;Y88F;H547A;Y88F 205;211;200;106;101 210;215;204;111;105 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. 2B, in comparison to WT hDAT, neither Bmax nor Kd values of [3H]WIN35,428 were altered in Y88F/H547A, whereas Y88F/K92M/H547A displayed a 61% decrease in the Bmax value (t(14) = 2.4, p < 0.05) and a 199% increase in the Kd value (t(14) = 4.4, p < 0.001). 2019 Scientific reports Result HIV H547A;K92M;Y88F;H547A;Y88F 120;115;110;95;90 125;119;114;100;94 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. According to our previous computational and experimental results, single mutation of either hDAT Y88 (Y88F), K92 (K92M) or H547 (H547A) could significantly attenuate the binding between DAT and Tat. 2019 Scientific reports Result HIV H547A;K92M;Y88F 129;114;102 134;118;106 Tat 194 197 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Addition of PMA reduced the Vmax values in WT hDAT by 51% [t(5) = 2.79, p < 0.05] and Y88F/H547A by 60% [t(5) = 3.90, p < 0.05], respectively, compared to their respective vehicle controls. 2019 Scientific reports Result HIV H547A;Y88F 91;86 96;90 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Additionally, compared to WT hDAT (1.21 +- 0.17 microM), the Km value in Y88F/H547A was increased by 250% (4.25 +- 1.05 microM, t(7) = 2.54, p < 0.05) but not altered in Y88F/K92F/H547A. 2019 Scientific reports Result HIV H547A;K92F;Y88F;H547A;Y88F 180;175;170;78;73 185;179;174;83;77 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. AMPH decreased the Vmax in both WT hDAT (32%, 7.80 +- 0.97 pmol/min/105 cells, t(8) = 2.76, p < 0.01) and Y88F/H547A (42%, 10.9 +- 1.33 pmol/min/105 cells, t(8) = 2.58, p < 0.05) compared with their respective controls. 2019 Scientific reports Result HIV H547A;Y88F 111;106 116;110 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. As shown in Table 3, the Vmax values of [3H]DA efflux in response to AMPH were reduced in H547A (0.22 +- 0.04) and Y88F/H547A (0.20 +- 0.03) compared to WT hDAT (0.42 +- 0.03, ps < 0.05, Bonferroni's multiple comparison test). 2019 Scientific reports Result HIV H547A;H547A;Y88F 90;120;115 95;125;119 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Compared to the controls, AMPH significantly increased the Km value in WT hDAT [4.08 +- 0.56 microM; t(8) = 4.63, p < 0.01], which was attenuated in Y88F/H547A (7.24 +- 1.15 microM). 2019 Scientific reports Result HIV H547A;Y88F 154;149 159;153 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Compared to the respective controls (in absence of Zn2+), the addition of Zn2+ (10 and 100 microM) produced a similar reduction of [3H]DA uptake in WT (~40%, ps < 0.01) but a greater reductions (60% and 71% at 10 and 100 microM, respectively) in Y88F/H547A (ps < 0.01). 2019 Scientific reports Result HIV H547A;Y88F 251;246 256;250 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Compared to WT hDAT, Y88F/H547A increased the IC50 values for DA (WT hDAT: 2291 +- 487.3 nM; Y88F/H547A: 7236 +- 1825 nM) and cocaine (WT hDAT: 235 +- 53.3; Y88F/H547A: 1494 +- 333.0 nM, t(12) = 3.73, p < 0.001]. 2019 Scientific reports Result HIV H547A;H547A;H547A;Y88F;Y88F;Y88F 26;98;162;21;93;157 31;103;167;25;97;161 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Due to the difference in the specific [3H]DA uptake between WT hDAT and Y88F/H547A mutants. 2019 Scientific reports Result HIV H547A;Y88F 77;72 82;76 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Effect of Y88F/H547A on basal PKC-mediated regulation of DAT function. 2019 Scientific reports Result HIV H547A;Y88F 15;10 20;14 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. For example, two hydrogen bonds in the DAT-Tat interface were eliminated by double mutation of Y88F/H547A on hDAT. 2019 Scientific reports Result HIV H547A;Y88F 100;95 105;99 Tat 43 46 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. However, the Tat-induced reduction of [3H] DA uptake in WT hDAT was attenuated in Y88F/H547A compared to its control [t(4) = 0.42, p > 0.05], suggesting that the double mutation of Tyr88 and His547 attenuates Tat's inhibitory effect on DA uptake. 2019 Scientific reports Result HIV H547A;Y88F 87;82 92;86 Tat;Tat 13;209 16;212 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. In comparison to WT hDAT, Y88F/H547A reduced the apparent affinity (IC50) for DA [WT hDAT: 2063 +- 582.5 nM; Y88F/H547A: 7918 +- 637.6 nM; t(10) = 6.78, p < 0.0001]. 2019 Scientific reports Result HIV H547A;H547A;Y88F;Y88F 31;114;26;109 36;119;30;113 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. In contrast, compared to WT hDAT, Y88F/ H547A displayed an increase in IC50 for cocaine [WT hDAT: 350 +- 49.4 nM; H547A/Y88F: 131 +- 13.9 nM; t(6) = 4.28, p < 0.01] and GBR12909 [WT hDAT: 511 +- 56.6 nM; Y88F/H547A: 253 +- 40.4 nM; t(8) = 3.71, p < 0.01]. 2019 Scientific reports Result HIV H547A;H547A;H547A;Y88F;Y88F;Y88F 40;114;209;34;120;204 45;119;214;38;124;208 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. In the absence of AMPH, the Km values of [3H]DA uptake was greater in Y88F/H547A (5.12 +- 0.76 microM) than that in WT hDAT [1.43 +- 0.15 microM, t(8) = 4.79, p < 0.01). 2019 Scientific reports Result HIV H547A;Y88F 75;70 80;74 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. In the current study, we also found that Y88F/H547A displayed increased the Vmax relative to WT hDAT. 2019 Scientific reports Result HIV H547A;Y88F 46;41 51;45 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Next, we performed the kinetic analysis of [3H]DA uptake in WT and Y88F/H547A in presence of AMPH (1 microM, final concentration). 2019 Scientific reports Result HIV H547A;Y88F 72;67 77;71 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. No difference in IC50 GBR12909 inhibiting [3H]WIN35,428 binding was observed between WT hDAT and Y88F/H547A. 2019 Scientific reports Result HIV H547A;Y88F 102;97 107;101 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Our previous studies demonstrated that single point mutation of Tyr88 (Y88F) or His547 (H547A) attenuated Tat-induced inhibition of [3H]DA uptake observed in WT hDAT. 2019 Scientific reports Result HIV H547A;Y88F 88;71 93;75 Tat 106 109 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Post hoc analyses show that the Vmax value in Y88F/H547A (18.9 +- 2.81 pmol/min/105 cells) was higher than that in WT hDAT (11.5 +- 0.94 pmol/min/105 cells, t(8) = 2.49, p < 0.05, n = 5/group) in the absence of AMPH. 2019 Scientific reports Result HIV H547A;Y88F 51;46 56;50 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Since the triple mutant (Y88F/K92M/H547A) displayed an extremely low Vmax of [3H]DA uptake, only the double mutant (Y88F/H547A) was tested for its effect on Tat-induced inhibition of DA uptake. 2019 Scientific reports Result HIV H547A;K92M;Y88F;H547A;Y88F 35;30;25;121;116 40;34;29;126;120 Tat 157 160 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. The addition of 1 microM PMA reduced Km values by 53% in WT hDAT [t(5) = 3.31, p < 0.05] and 63% in Y88F/H547A [t(5) = 2.54, p < 0.05], respectively. 2019 Scientific reports Result HIV H547A;Y88F 105;100 110;104 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. The Zn2+ (10 and 100 microM)-induced increase in [3H]WIN 35,428 binding in WT hDAT was significantly diminished in Y88F/H547A [1 microM, t(16) = 2.37, p < 0.05; 10 microM, t(16) = 3.23, p < 0.01; 100 microM, t(16) = 3.57, p < 0.01], suggesting that Y88F/H547A attenuates zinc-induced increase in [3H]WIN35,428 of hDAT by altering transporter conformational transitions. 2019 Scientific reports Result HIV H547A;H547A;Y88F;Y88F 120;254;115;249 125;259;119;253 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. There was a significant difference in the magnitude of the AMPH-induced decrease in Vmax values between WT hDAT and Y88F/H547A (t(8) = 1.86, p < 0.05). 2019 Scientific reports Result HIV H547A;Y88F 121;116 126;120 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Therefore, one may expect that Y88F/H547A and Y88F/K92M/H547A mutants are more effective in inhibiting DAT-Tat binding than single point mutations of Y88F, K92M and H547A. 2019 Scientific reports Result HIV H547A;K92M;Y88F;H547A;H547A;K92M;Y88F;Y88F 56;51;46;36;165;156;31;150 61;55;50;41;170;160;35;154 Tat 107 110 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. These results suggest that the double mutation of Tyr88 and His547 attenuates the single mutant H547A-increased sensitivity of PMA-induced decrease in DA uptake. 2019 Scientific reports Result HIV H547A 96 101 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Thus, due to the significant reduction on DA uptake for Y88F/K92M/H547A, only the Y88F/H547A mutant was included for the rest of experiments. 2019 Scientific reports Result HIV H547A;K92M;Y88F;H547A;Y88F 66;61;56;87;82 71;65;60;92;86 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. To characterize the influence of Y88F/H547A on DA transport and the specific binding site in hDAT for DA, cocaine, GBR12909, and amphetamine (AMPH), we determined the ability of these DAT inhibitors or substrate to inhibit [3H] DA uptake in WT hDAT and Y88F/H547A (Table 1). 2019 Scientific reports Result HIV H547A;H547A;Y88F;Y88F 38;258;33;253 43;263;37;257 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. To determine whether the His547 residue still acts as a potential site for the regulation of Tat-DAT in Y88F/H547A, we examined the effects of Y88F/H547A on zinc modulation of [3H]DA uptake and [3H]WIN35,428 binding. 2019 Scientific reports Result HIV H547A;H547A;Y88F;Y88F 109;148;104;143 114;153;108;147 Tat 93 96 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. To further determine the effect of Tyr88/His547 mutation on transporter conformational transitions, we examined basal efflux levels of [3H]DA in PC12 cells expressing WT hDAT and Y88F/H547A. 2019 Scientific reports Result HIV H547A;Y88F 184;179 189;183 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. two-way ANOVA analysis on the specific [3H]DA uptake in WT hDAT and Y88F/H547A revealed significant main effects of mutation [F(1, 12) = 55.34, p < 0.0001], zinc [F(3, 36) = 39.15, p < 0.0001], and mutation x zinc interaction [F(3, 36) = 3.70, p < 0.05]. 2019 Scientific reports Result HIV H547A;Y88F 73;68 78;72 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. We also evaluated the mutational effect of Y88F/H547A on the IC50 of DA, cocaine, and GBR12909 for inhibiting [3H]WIN35,428 binding (Table 2). 2019 Scientific reports Result HIV H547A;Y88F 48;43 53;47 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. We first examined the affinity for AMPH to inhibit [3H]DA uptake in WT and Y88F/H547A (Table 1), however, no significant difference in the IC50 value was found between WT (926 +- 167.4 nM) and Y88F/H547A [1279 +- 200.5 nM, t(8) = 1.32, p = 0.22]. 2019 Scientific reports Result HIV H547A;H547A;Y88F;Y88F 80;198;75;193 85;203;79;197 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. We have demonstrated that single point mutations on hDAT at His547 (H547A) and Lys92 (K92M) displayed a 196% increase and a 71% decrease in the Vmax of [3H]DA uptake, respectively, while Y88F preserved normal DA uptake. 2019 Scientific reports Result HIV H547A;K92M;Y88F 68;86;187 73;90;191 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. We have demonstrated that the addition of 1 microM PMA produced a 40% and 60% decrease in the Vmax of DA uptake in WT hDAT and H547A mutant, respectively, compared to the respective control, suggesting that H547A displays increased sensitivity to PMA-induced DAT phosphorylation. 2019 Scientific reports Result HIV H547A;H547A 127;207 132;212 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. We then determined whether Y88F/H547A-upregulated DA uptake is also mediated by alteration of sensitivity to PMA-induced DAT phosphorylation. 2019 Scientific reports Result HIV H547A;Y88F 32;27 37;31 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Another 21% (6 of 28) of participants had K103N minority variants at levels between 2% and 20% (total retention 71% [20 of 28]). 2019 Open forum infectious diseases Result HIV K103N 42 47 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Deep sequencing of proviral DNA demonstrated that 50% (14 of 28) of participants retained K103N at levels >20%. 2019 Open forum infectious diseases Result HIV K103N 90 95 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Differences between the plasma RNA and DNA identified by branch length in the tree were not different comparing the mean DNA-RNA genetic distance, between the 12 sequences with K103N in proviral DNA and the 14 sequences without K103N. 2019 Open forum infectious diseases Result HIV K103N;K103N 177;228 182;233 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Finally, K103N was not detected in the proviral DNA of 29% (8 of 28) participants who had K103N in plasma RNA at virologic failure. 2019 Open forum infectious diseases Result HIV K103N;K103N 9;90 14;95 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Frequency of participants with NNRTI and NRTI mutations as detected by Sanger sequencing by time point demonstrated only a modest decrease in the percentage of participants with detectable K103N over time (Figure 1). 2019 Open forum infectious diseases Result HIV K103N 189 194 NNRTI;NRTI 31;41 36;45 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. In an adjusted model including years since suppression, log10 plasma HIV RNA level at EFV failure was associated with increased likelihood of observing proviral K103N (P = .04); odds of detectable proviral K103N was 2.6 times higher (95% confidence interval, 1.0-6.4) per log10 higher HIV RNA at EFV failure. 2019 Open forum infectious diseases Result HIV K103N;K103N 161;206 166;211 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. It is interesting to note that M184V was retained in proviral DNA, whereas other NRTI DRM demonstrated modest decreases (Figure 2B). 2019 Open forum infectious diseases Result HIV M184V 31 36 NRTI 81 85 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Likewise, M184V was detected by deep sequencing at levels >20% in 25% (7 of 28) of participants, 14% (4 of 28) at levels between 2% and 20% [total retention 39% (11 of 28)], and was not detected in 61% (17 of 28) of participants. 2019 Open forum infectious diseases Result HIV M184V 10 15 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Sanger sequencing revealed that M184V was retained in 25% (7 of 28) of participants. 2019 Open forum infectious diseases Result HIV M184V 32 37 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Sanger sequencing showed that K103N was retained in a total of 61% (17 of 28) of participants. 2019 Open forum infectious diseases Result HIV K103N 30 35 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Sequences of plasma RNA at failure demonstrated high-level NNRTI DRM in all 28 participants with K103N; NRTI DRMs were identified in plasma RNA in 75% of these participants (Figure 1). 2019 Open forum infectious diseases Result HIV K103N 97 102 NNRTI;NRTI 59;104 64;108 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Sequencing at virologic failure included the K103N mutation among 28 participants. 2019 Open forum infectious diseases Result HIV K103N 45 50 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. The exceptions were participants with decay from high level to <20% (K103N, n = 2; M184V, n = 1), participants whose levels went from undetectable to >20% (K103N, n = 1; M184V, n = 1), and participants whose levels went from undetectable to >20% back to undetectable (K103N, n = 0; M184V, n = 1) (Figure 3). 2019 Open forum infectious diseases Result HIV K103N;K103N;K103N;M184V;M184V;M184V 69;156;268;83;170;282 74;161;273;88;175;287 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. The log10 virus load and CD4 count at virologic failure are shown in Table 1, as are the duration of suppression on LPV/r and 2 nucleosides and the evaluation of provirus K103N by Sanger and Illumina sequencing at the last available timepoint. 2019 Open forum infectious diseases Result HIV K103N 171 176 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. The virus load at the time of confirmed virologic failure (at the identification of the K103N mutation) varied from 2.73 to 5.99 log10 copies/mL ethylenediaminetetraacetic acid plasma (geometric mean, 4.04 log10 copies/mL; median, 3.98 log10 copies/mL; IQR, 3.43-4.55 log10 copies/mL). 2019 Open forum infectious diseases Result HIV K103N 88 93 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. We also used deep sequencing to analyze K103N and M184V levels within individuals to assess persistence and decay over time. 2019 Open forum infectious diseases Result HIV K103N;M184V 40;50 45;55 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Years since start of suppression was not associated with the likelihood of detectable K103N (P = .53). 2019 Open forum infectious diseases Result HIV K103N 86 91 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. Finally, a single patient had Q129R mutation that is a vaccine-escape mutant and affects HBV detection besides the R122K mutation. 2019 PeerJ Result HIV R122K 115 120 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. The L109R mutation that is a vaccine-escape mutant was found in a single patient. 2019 PeerJ Result HIV L109R 4 9 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. The M133L and D144E mutations that are vaccine-escape mutants, affecting HBV detection and immunoglobulin therapy were found each in a single patient. 2019 PeerJ Result HIV M133L 4 9 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. The R122K mutation which affects HBV detection was found in three patients. 2019 PeerJ Result HIV R122K 4 9 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. The S143L mutation which is both a vaccine-escape mutant and affects HBV detection was found in a single patient. 2019 PeerJ Result HIV S143L 4 9 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. As shown in Table 2 Group A, B and C, the very high prevalence of resistance to 3TC and FTC were due to the high rate of M184 V mutation. 2019 BMC infectious diseases Result HIV M184V 121 127 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Interestingly, up to 83.2% of patients harboured the M184 V mutation, associated with high-level resistance to 3TC and FTC and serving as adherence marker. 2019 BMC infectious diseases Result HIV M184V 53 59 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Of note, L74I (following exposure to TDF-containing regimens) and L210 W (following exposure to regimens containing a thymidine analogue) mutations were found only in the group of patients infected with CRF02_AG viruses. 2019 BMC infectious diseases Result HIV L210W;L74I 66;9 72;13 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Of note, TAMs-1 were predominant (T215F/Y: 46.5%; M41 L: 22.8%; L210 W: 8.9%) and associated with higher levels of resistance to both AZT and TDF; as compared to TAMs-2 that had relatively lower prevalence (D67N: 21.8%; K70R: 19.8%; K219Q/E: 18.8%) and were associated preferentially with AZT/D4T-resistance. 2019 BMC infectious diseases Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 207;233;233;220;64;50;34;34 211;240;240;224;70;55;42;42 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. TDF-mutation K65R was significantly associated with TDF-exposure: 0% in group-A, 22.7% (5/22) in group-B, 4.2% (1/24) in group-C (p = 0.0013). 2019 BMC infectious diseases Result HIV K65R 13 17 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Another HIV-1 strain displayed the accessory mutations G140R and L74I, and three APOBEC-related mutations: G70R, G149R and G247R. 2019 The Journal of antimicrobial chemotherapy Result HIV G140R;G149R;G247R;G70R;L74I 55;113;123;107;65 60;118;128;111;69 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. DRMs to PIs corresponded mainly to natural polymorphism in the P gene while only the major DRMs V82A/F (n = 3; 20%) and L33F (n = 1, 6.7%) could be found. 2019 The Journal of antimicrobial chemotherapy Result HIV L33F;V82A;V82F 120;96;96 124;102;102 PI 8 11 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Finally, the unusual polymorphic mutation T112E was found in the HIV-1 strain harbouring the E138T DRM. 2019 The Journal of antimicrobial chemotherapy Result HIV E138T;T112E 93;42 98;47 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. In addition, the HIV-1 strain harbouring the E138K DRM also displayed accessory mutations G140K, G163R (Table 2) and APOBEC-related mutations not associated with resistance, including G82E, E85K, G106K, D116N, D167N and E170K. 2019 The Journal of antimicrobial chemotherapy Result HIV D116N;D167N;E138K;E170K;E85K;G106K;G140K;G163R;G82E 203;210;45;220;190;196;90;97;184 208;215;50;225;194;201;95;102;188 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. One HIV-1 strain showed the DRM E138K and the other showed E138T, which are both associated with potential low-level resistance (mutation score, 10) to dolutegravir and low-level resistance (mutation score, 15) to raltegravir and elvitegravir according to the Stanford University algorithm (Table 2). 2019 The Journal of antimicrobial chemotherapy Result HIV E138K;E138T 32;59 37;64 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Polymorphic mutations in the IN gene were frequently observed: L101I/M, TT124A/G/N and T125A/P/V (100%) were the most represented, followed by G134D/N/S and L234I/P/V (94.4%); T112A/E/I/T/V (83.3%), D167E/N (77.7%), K136R/Q/T (66.7%), I72V (50.0%), S255D/G/N (38.9%), N222K/T, T206S and T218I/L/S (33.3%); and I135V, I208L and S119P (27.7%). 2019 The Journal of antimicrobial chemotherapy Result HIV D167E;D167N;G134D;G134N;G134S;I135V;I208L;I72V;K136Q;K136R;K136T;L101I;L101M;L234I;L234P;L234V;N222K;N222T;S119P;S255D;S255G;S255N;T112A;T112E;T112I;T112T;T112V;T125A;T125P;T125V;T206S;T218I;T218L;T218S 199;199;143;143;143;310;317;235;216;216;216;63;63;157;157;157;268;268;327;249;249;249;176;176;176;176;176;87;87;87;277;287;287;287 206;206;152;152;152;315;322;239;225;225;225;70;70;166;166;166;275;275;332;258;258;258;189;189;189;189;189;96;96;96;282;296;296;296 IN 29 31 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. The following unusual mutations were also found in an HIV-1 strain: L234P, P238G, K240E, G247E, A248G and D256G. 2019 The Journal of antimicrobial chemotherapy Result HIV A248G;D256G;G247E;K240E;L234P;P238G 96;106;89;82;68;75 101;111;94;87;73;80 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. 2 template/primer (T/P), the ability of G112D RT to extend a primer was similar to that of WT RT at both the low and the high dNTP concentrations. 2019 Journal of virology Result HIV G112D 40 45 RT;RT 46;94 48;96 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. 5D) or M230I HIV-1. 2019 Journal of virology Result HIV M230I 7 12 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. A possible explanation for the difference seen in the in vitro data and the virological data is that the improvement in the replication of virus carrying both mutations, compared to M230I alone, is somewhat small. 2019 Journal of virology Result HIV M230I 182 187 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Addition of the FTC resistance mutation M184V to M230I (M184V/M230I HIV-1) produced the expected loss of susceptibility to FTC but did not affect the susceptibility of the virus to AZT or RPV (data not shown). 2019 Journal of virology Result HIV M184V;M184V;M230I;M230I 40;56;49;62 45;61;54;67 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. After 59 days of infection, viral RNA was isolated and the G112D and G196R mutations were detected in RT (Table 1). 2019 Journal of virology Result HIV G112D;G196R 59;69 64;74 RT 102 104 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. As described above, the addition of G112D to the mutation M230I decreases the susceptibility of the RT to inhibition by NNRTIs. 2019 Journal of virology Result HIV G112D;M230I 36;58 41;63 NNRTI;RT 120;100 126;102 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. As noted earlier, this is a surprising result, because G112D is near the polymerase active site and is a considerable distance from M230I (>10.0 A). 2019 Journal of virology Result HIV G112D;M230I 55;132 60;137 Pol 73 83 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. At both dNTP concentrations, G112D RT appeared to have activity similar to that of WT RT. 2019 Journal of virology Result HIV G112D 29 34 RT;RT 35;86 37;88 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Because G112D is near the active site, we evaluated the effects of this mutation, with or without M230I, on the sensitivity of HIV-1 to different nucleoside analogs (Table 3). 2019 Journal of virology Result HIV G112D;M230I 8;98 13;103 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Because M230I is in a position to interact with the primer strand of the T/P, it is possible that this mutation could negatively affect the stability of the binding of the M230I-containing RTs to the nucleic acid substrate. 2019 Journal of virology Result HIV M230I;M230I 8;172 13;177 RT 189 192 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Because the M230I reduces the ability of RT to excise, it is not surprising that AZT susceptibility is not further reduced by the M184V/M230I double mutant. 2019 Journal of virology Result HIV M184V;M230I;M230I 130;12;136 135;17;141 RT 41 43 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Both G112D and G112D/M230I RTs showed only very limited excision ability using ATP. 2019 Journal of virology Result HIV G112D;G112D;M230I 5;15;21 10;20;26 RT 27 30 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Both G112D and the double mutant caused hypersensitivity to PFA but had only a modest effect on susceptibility to ddI and TFV. 2019 Journal of virology Result HIV G112D 5 10 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Compound 13 selects G112D and M230I in HIV-1 RT. 2019 Journal of virology Result HIV G112D;M230I 20;30 25;35 RT 45 47 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D alone did not alter the susceptibility of the virus to any of these NNRTIs; in contrast, M230I caused a 7- to 11-fold decrease in susceptibility. 2019 Journal of virology Result HIV M230I;G112D 95;0 100;5 NNRTI 74 80 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D alone does not reduce susceptibility to NNRTIs but does reduce susceptibility to NNRTIs in combination with M230I. 2019 Journal of virology Result HIV M230I;G112D 114;0 119;5 NNRTI;NNRTI 46;87 52;93 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D and M230I affect the sensitivity of HIV-1 to NRTIs in different ways. 2019 Journal of virology Result HIV M230I;G112D 10;0 15;5 NRTI 51 56 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D enhances HIV-1 replication in combination with M230I. 2019 Journal of virology Result HIV M230I;G112D 53;0 58;5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D is located approximately 10.0 A from the NNRTI binding region and is not in a position where it could interact directly with a bound NNRTI or with M230I. 2019 Journal of virology Result HIV M230I;G112D 153;0 158;5 NNRTI;NNRTI 47;139 52;144 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D reduced the susceptibility of the virus to FTC 16-fold, while M230I conferred hypersensitivity. 2019 Journal of virology Result HIV M230I;G112D 68;0 73;5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D RT showed only a slight reduction in sensitivity to the inhibitor. 2019 Journal of virology Result HIV G112D 0 5 RT 6 8 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D RT was also potently inhibited by compound 13. 2019 Journal of virology Result HIV G112D 0 5 RT 6 8 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D/M184V HIV-1 was not infectious and could not be characterized in cell culture assays. 2019 Journal of virology Result HIV M184V;G112D 6;0 11;5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. However, because some mutations can be selected if they improve the replication of an unfit virus, we performed competition experiments with HIV-1 molecular clones that encode WT RT, the G112D and M230I mutations by themselves, or both mutations in HuT-R5 cells in the absence of inhibitor. 2019 Journal of virology Result HIV G112D;M230I 187;197 192;202 RT 179 181 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. However, G112D RT was relatively insensitive to FTCTP and M230I RT was hypersensitive. 2019 Journal of virology Result HIV G112D;M230I 9;58 14;63 RT;RT 15;64 17;66 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. However, M230 is also near the NNRTI binding site, and the M230I mutation is in a position to interact directly with compound 13. 2019 Journal of virology Result HIV M230I 59 64 NNRTI 31 36 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. However, the data show that while G112D has little effect on the susceptibility of RT to an NNRTI by itself, the acquisition of this mutation in the presence of M230I can reduce the susceptibility of RT to NNRTI inhibition. 2019 Journal of virology Result HIV G112D;M230I 34;161 39;166 NNRTI;NNRTI;RT;RT 92;206;83;200 97;211;85;202 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. It is possible that G112D and/or M230I could reduce this intrinsic excision ability, which would explain the hypersensitivity of the mutant viruses to AZT. 2019 Journal of virology Result HIV G112D;M230I 20;33 25;38 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M184V causes reduced residual excision by RT. 2019 Journal of virology Result HIV M184V 0 5 RT 42 44 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I had a deleterious effect on polymerization at both the low and high concentrations of dNTPs with both of the DDDP substrates. 2019 Journal of virology Result HIV M230I 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I HIV-1 was also hypersensitive to didanosine (ddI), an adenosine analog; to tenofovir (TFV), an adenosine nucleotide analog; and to phosphonoformic acid (PFA), a pyrophosphate analog. 2019 Journal of virology Result HIV M230I 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I RT again had decreased polymerase activity compared to that of WT RT. 2019 Journal of virology Result HIV M230I 0 5 Pol;RT;RT 29;6;72 39;8;74 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I RT was better at excision but was still less excision proficient than WT RT. 2019 Journal of virology Result HIV M230I 0 5 RT;RT 6;79 8;81 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I was introduced into a molecular clone and selection was performed with compound 13 to determine whether G112D would be selected again. 2019 Journal of virology Result HIV G112D;M230I 110;0 115;5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I was selected by RPV in cell culture but is rarely seen in HIV-infected individuals. 2019 Journal of virology Result HIV M230I 0 5 HIV infections 64 76 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Position 112 is located near the polymerase active site, but it is on the opposite side from both M230I and a bound NNRTI. 2019 Journal of virology Result HIV M230I 98 103 Pol;NNRTI 33;116 43;121 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. RNA and DNA molecules were cloned and sequenced, and the results showed that G112D and M230I were linked on the same genomes, suggesting that both mutations contributed to the observed loss of potency of the compound. 2019 Journal of virology Result HIV G112D;M230I 77;87 82;92 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. RTs containing G112D, M230I, or the double mutation G112D/M230I were introduced into a molecular clone of HIV-1, and their effects on the potencies of compound 13, RPV, EFV, etravirine (ETR), and NVP were measured (Table 2). 2019 Journal of virology Result HIV G112D;G112D;M230I;M230I 15;52;22;58 20;57;27;63 RT 0 3 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The ability of the mutations to reduce the susceptibility of RT to NNRTIs was examined using a [alpha-32P]dCTP incorporation assay, comparing WT RT with each of the RT variants (G112D, M230I, or G112D/M230I) in the presence of NVP or compound 13. 2019 Journal of virology Result HIV G112D;G112D;M230I;M230I 178;195;185;201 183;200;190;206 NNRTI;RT;RT;RT 67;61;145;165 73;63;147;167 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The addition of the G112D mutation to M230I increased the EC50 values for compound 13 and RPV 3-fold, for EFV and ETR 2-fold, and for NVP 1.5-fold compared to the value with M230I alone. 2019 Journal of virology Result HIV G112D;M230I;M230I 20;38;174 25;43;179 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The behavior of the double mutant was similar to that of M230I RT. 2019 Journal of virology Result HIV M230I 57 62 RT 63 65 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The difference in the results of the two assays is not sufficient to suggest decreased nucleic acid binding ability for the M230I-containing mutants. 2019 Journal of virology Result HIV M230I 124 129 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The double mutant G112/M230I HIV-1 replicated better than either G112D HIV-1. 2019 Journal of virology Result HIV M230I;G112D 23;65 28;70 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The double mutant was slightly less active than M230I RT. 2019 Journal of virology Result HIV M230I 48 53 RT 54 56 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The fact that the M230I mutation affects the incorporation of both FTCTP and 3TCTP, taken together with the fact that G112D acts to compensate for the effects of the M230I mutation on the incorporation of these analogs, provides additional support for the proposal, made earlier, that M230I affects the positioning of the nucleic acid substrate at the active site. 2019 Journal of virology Result HIV G112D;M230I;M230I;M230I 118;18;166;285 123;23;171;290 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The order of susceptibility (from least to most) is G112D/M230I > M230I > G112D > WT. 2019 Journal of virology Result HIV G112D;G112D;M230I;M230I 52;74;58;66 57;79;63;71 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The previously described RPV-associated mutation K101E was detected in the RPV selected cultures by sequencing viral RNA after 56 days, when the drug was present at 128-fold above the EC50. 2019 Journal of virology Result HIV K101E 49 54 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The RT data were similar to the virology data, showing that M230I RT was less susceptible to NVP than WT RT and G112D/M230I RT was less susceptible than M230I RT. 2019 Journal of virology Result HIV G112D;M230I;M230I;M230I 112;60;118;153 117;65;123;158 RT;RT;RT;RT;RT 4;66;105;124;159 6;68;107;126;161 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. These data indicate that while the M230I mutation had a deleterious effect on the polymerase activity in vitro, G112D did not help correct this deficiency. 2019 Journal of virology Result HIV G112D;M230I 112;35 117;40 Pol 82 92 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. These results show that G112D was selected in three independent cultures with M230I, suggesting that both amino acid substitutions provide an advantage for HIV-1 replication in the presence of compound 13. 2019 Journal of virology Result HIV G112D;M230I 24;78 29;83 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. These results suggest that G112D not only reduces the susceptibility of the M230I HIV-1 to NNRTIs but also enhances the replication of the mutant. 2019 Journal of virology Result HIV G112D;M230I 27;76 32;81 NNRTI 91 97 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. These results suggest that the hypersensitivity seen in virology assays is probably caused by the fact that both mutations, especially G112D, reduce the ability of RT to excise AZTMP. 2019 Journal of virology Result HIV G112D 135 140 RT 164 166 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. When CPE were finally observed, bulk sequencing of viral RNA and DNA from both compound 13 cultures consistently identified RT mutations G112D and M230I; G112D was detected first in one of the cultures (Table 1). 2019 Journal of virology Result HIV G112D;G112D;M230I 137;154;147 142;159;152 RT 124 126 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. While compound 13 still affected the polymerase activity of the mutant RTs, M230I RT and the double mutant were less susceptible to inhibition than WT RT. 2019 Journal of virology Result HIV M230I 76 81 Pol;RT;RT;RT 37;71;82;151 47;74;84;153 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. WT RT and G112D/M230I RT showed similar sensitivities to FTC triphosphate (FTCTP). 2019 Journal of virology Result HIV G112D;M230I 10;16 15;21 RT;RT 3;22 5;24 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. WT RT was inhibited by NVP, while G112D RT appeared to be slightly hypersensitive. 2019 Journal of virology Result HIV G112D 34 39 RT;RT 3;40 5;42 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. WT, M230I, and G112D/M230I RTs were fully sensitive to zidovudine triphosphate (AZTTP). 2019 Journal of virology Result HIV G112D;M230I;M230I 15;4;21 20;9;26 RT 27 30 30937190 Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India. One isolate, belonging to MSM, had L74V, a NRTI resistance mutation that is known to cause Intermediate Resistance to Abacavir (ABC). 2019 AIDS research and treatment Result HIV L74V 35 39 NRTI 43 47 30937190 Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India. Out of 6 resistant isolates, 3 had a NRTI resistance mutation (K219R:2; K219N:1) that is known to cause potential low level resistance to Zidovudine (AZT). 2019 AIDS research and treatment Result HIV K219N;K219R 72;63 77;68 NRTI 37 41 30937190 Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India. Two isolates had Y181C, a major NNRTI resistance mutation accountable for high level resistance to Nevirapine (NVP), intermediate resistance to efavirenz (EFV), etravirine (ETR), and rilpivirine (RPV). 2019 AIDS research and treatment Result HIV Y181C 17 22 NNRTI 32 37 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. 1a), we compared the affinity of recombinant wild type and mutant CypA (A25D, K27D, P29K and K30D) for unassembled CA, cross-linked CA hexamers and self-assembled CA tubes. 2019 Retrovirology Result HIV A25D;K27D;K30D;P29K 72;78;93;84 76;82;97;88 Capsid;Capsid;Capsid 115;132;163 117;134;165 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. 1D 1H spectra of CypA A25K and P29D mutants (not shown) and 2D 1H-15N HSQC NMR spectrum of 15N/13C-labeled CypA P29K mutant (Additional file 1: Figure S2B) reveal that the structures of the mutants are essentially the same as for wild type protein (Additional file 1: Figure S2A), whereby perturbations were confined to the mutated site and neighbouring residues while the active site was intact. 2019 Retrovirology Result HIV A25K;P29D;P29K 22;31;112 26;35;116 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Additional mutants at these residues (A25K, K27A and P29D) were also tested in the infection assays. 2019 Retrovirology Result HIV A25K;K27A;P29D 38;44;53 42;48;57 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Biophysical characterization of purified proteins by differential scanning fluorimetry and circular dichroism (Additional file 1: Figure S1) showed that mutants A25D, K27D and P29K were similar to wild type CypA with respect to melting point and secondary structure content, whereas CypA K30D was destabilized, possibly as a result of removing the interaction of K30 with E83 as discussed above. 2019 Retrovirology Result HIV A25D;K27D;K30D;P29K 161;167;288;176 165;171;292;180 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. CA tubes were grown inside a microfluidic flow-channel in a high salt solution by co-assembly of CA A14C/E45C and CA K158C modified with AlexaFluor 488 (for fluorescence labeling of the tubes) and immobilized onto the modified surface of the glass cover slip via an antibody directed against the CypA loop of CA. 2019 Retrovirology Result HIV A14C;E45C;K158C 100;105;117 104;109;122 Capsid;Capsid;Capsid;Capsid 0;97;114;309 2;99;116;311 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Expression of CypA P29K also enhanced HIV-1 infection close to wild-type levels, while CypA P29D did not restore permissiveness to infection, possibly because the expression level of this mutant was too low in CypA-null Jurkat cells (approximately half of the expression level of wild type CypA in CypA-null Jurkat cells. 2019 Retrovirology Result HIV P29D;P29K 92;19 96;23 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Expression of CypA proteins with mutations in secondary site residues A25 and K27 in CypA-null Jurkat cells restored their permissiveness to infection by wild type HIV-1 close to the level observed for wild type CypA, while the destabilized mutant CypA K30D showed partial enhancement of infectivity (see also Additional file 1: Figure S4). 2019 Retrovirology Result HIV K30D 253 257 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Finally, we chose CypA A25D as one of the secondary site mutants without folding defects to determine whether its interaction with the wild type CA lattice of authentic viral cores was impaired compared to wild type CypA. 2019 Retrovirology Result HIV A25D 23 27 Capsid 145 147 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. In addition, these mutations, as well as K27A, change the steric configuration at these sites. 2019 Retrovirology Result HIV K27A 41 45 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. In additional experiments, expression of the P29D and P29K mutants was undetectable, and the phenotype of the corresponding cell lines was identical to that of the CypA-null cells (Additional file 1: Figure S4). 2019 Retrovirology Result HIV P29D;P29K 45;54 49;58 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. In the following sections we present results from infection assays in (1) HeLa-P4 cells (using HIV-1 with CA A92E mutation) and (2) Jurkat cells. 2019 Retrovirology Result HIV A92E 109 113 Capsid 106 108 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. K30D would also be expected to locally destabilise the structure by breaking the interaction of K30 with E83 that is apparent in the crystal structure of wild type CypA. 2019 Retrovirology Result HIV K30D 0 4 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Moreover, the binding property of CypA P29K (Additional file 1: Figure S2D) to CA-NTD, studied by 1H-15N HSQC, was the same as for wild type protein (Additional file 1: Figure S2C). 2019 Retrovirology Result HIV P29K 39 43 Capsid 79 81 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Similarly, the 1H-15N HSQC spectral perturbations of 15N/13C-labeled CA-NTD upon adding unlabeled CypA P29K, P29D and A25K were similar (not shown). 2019 Retrovirology Result HIV A25K;P29D;P29K 118;109;103 122;113;107 Capsid 69 71 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. The destabilized mutant K30D showed only a minor defect in binding via the active site with a 1.5:twofold increase in KD compared to the other variants. 2019 Retrovirology Result HIV K30D 24 28 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. The HIV-1 capsid escape mutant A92E arises during passage of HIV-1 in HeLa-P4 cells during CypA inhibition and is poorly infective in cells expressing high CypA levels such that its replication becomes dependent on the presence of the CypA inhibitor cyclosporin A (CsA). 2019 Retrovirology Result HIV A92E 31 35 Capsid 10 16 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. The KD of CypA A25D binding to intact capsids (8.7 +- 2.1 muM) was not significantly different from the KD measured for wild type CypA in the same system (10.7 +- 0.7 muM). 2019 Retrovirology Result HIV A25D 15 19 Capsid 38 45 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. The KD values for mutants A25D, K27D and P29K interacting with unassembled or hexameric CA were similar to the values observed for wild type CypA (Table 1) confirming that these mutations did not affect the integrity of the active site. 2019 Retrovirology Result HIV A25D;K27D;P29K 26;32;41 30;36;45 Capsid 88 90 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. There was no statistically significant difference in the affinity of the interaction between CypA and CA tubes for wild type (KD ~ 15 muM) and mutant CypA (KD ~ 16-18 muM), including the destabilized mutant K30D. 2019 Retrovirology Result HIV K30D 207 211 Capsid 102 104 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. These tubes can be stabilized to prevent disassembly at physiological salt concentrations by using a double cysteine mutant (CA A14C/E45C) that forms disulfide cross-links between adjacent CA subunits in each hexamer. 2019 Retrovirology Result HIV A14C;E45C 128;133 132;137 Capsid;Capsid 125;189 127;191 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. We generated single site CypA mutants (A25D, K27D, P29K and K30D) at four residues located at the secondary CA contact site. 2019 Retrovirology Result HIV A25D;K27D;K30D;P29K 39;45;60;51 43;49;64;55 Capsid 108 110 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Wild type CypA and CypA mutants A25D, A25K, K27A, K27D, P29K and K30D could be expressed in the CypA-null cells at near or above endogenous levels. 2019 Retrovirology Result HIV A25D;A25K;K27A;K27D;K30D;P29K 32;38;44;50;65;56 36;42;48;54;69;60 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. In addition, nearly half of (49.1%, 27/55) HIV-1 strains with PDR mutation exhibited the degree of potential low-level resistance to NNRTI ascribed to V179D/E. 2019 BMC infectious diseases Result HIV V179D;V179E 151;151 158;158 NNRTI 133 138 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. M184 V (2.8%, 9/317) was the most prevalent NRTI associated mutation, followed by K65R (2.2%, 7/317). 2019 BMC infectious diseases Result HIV K65R;M184V 82;0 86;6 NRTI 44 48 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. PI resistance were detected in only two samples, being simultaneously resistant to ATV/r and LPV/r at a potential low level caused by M46I/L mutation. 2019 BMC infectious diseases Result HIV M46I;M46L 134;134 140;140 PI 0 2 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. The most frequent NNRTI associated mutation was V179D/E, which was observed in 10.1% (32/317) of patients, followed by Y181C (2.5%, 8/55) and K103 N (1.9%, 6/317). 2019 BMC infectious diseases Result HIV K103N;V179D;V179E;Y181C 142;48;48;119 148;55;55;124 NNRTI 18 23 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. In one patient who was receiving a ritonavir-boosted PI-based regimen, we observed two PI-associated RAMs (M46I and I82A). 2019 The Journal of antimicrobial chemotherapy Result HIV I82A;M46I 116;107 120;112 PI;PI 53;87 55;89 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. No PDR mutations were observed to PIs and only the polymorphism E157Q with minimal effect on INSTI susceptibility was observed in three patients. 2019 The Journal of antimicrobial chemotherapy Result HIV E157Q 64 69 INSTI;PI 93;34 98;37 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. No RAMs were observed to INSTIs; only the polymorphisms E157Q (n = 2), G163KR (n = 2) and T97A (n = 1) were observed, which have minimal effect on INSTI susceptibility. 2019 The Journal of antimicrobial chemotherapy Result HIV E157Q;G163K;G163R;T97A 56;71;71;90 61;77;77;94 INSTI;INSTI 25;147 31;152 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. Other mutations observed with a frequency of 2.0% were as follows: for NRTIs, D67N (n = 1), K70R (n = 1) and K219E (n = 1); and for NNRTIs, V106AM (n = 1) and G190A (n = 1) (Figure 1). 2019 The Journal of antimicrobial chemotherapy Result HIV D67N;G190A;K219E;K70R;V106A;V106M 78;159;109;92;140;140 82;164;114;96;146;146 NNRTI;NRTI 132;71 138;76 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. The most prevalent RT PDR mutations were as follows: K103N (n = 7, 14.3%), M184V (n = 4, 8.2%) and Y181C (n = 2, 4.1%). 2019 The Journal of antimicrobial chemotherapy Result HIV K103N;M184V;Y181C 53;75;99 58;80;104 RT 19 21 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. The most prevalent RT RAMs were as follows: K103N (n = 24, 40.7%), M184V (n = 17, 28.8%), D67N (n = 9, 15.3%), T215I/F/Y (n = 9, 15.3%) and M41L (n = 7, 11.9%) (Figure 1). 2019 The Journal of antimicrobial chemotherapy Result HIV D67N;K103N;M184V;M41L;T215F;T215I;T215Y 90;44;67;140;111;111;111 94;49;72;144;120;120;120 RT 19 21 30989237 Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone. The mutation L33F was observed in two patients; however, this mutation has minimal impact on PI susceptibility. 2019 The Journal of antimicrobial chemotherapy Result HIV L33F 13 17 PI 93 95 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. 1), resulting in the more rigid conformation of the active center and the reduced ability of both integrases to adapt to the G118R mutation. 2019 Acta naturae Result HIV G118R 125 130 IN 98 108 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. E11D (93.8%), K14R (81.3%), S24N (100%), and M50I (75%), were found. 2019 Acta naturae Result HIV K14R;M50I;S24N;E11D 14;45;28;0 18;49;32;4 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Genetic constructions with the drug resistance mutations G118R/E138K and Q148K/G140S were obtained by site-directed mutagenesis of pET-15b_IN_CRF. 2019 Acta naturae Result HIV E138K;G118R;G140S;Q148K 63;57;79;73 68;62;84;78 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. IN_CRF differs from IN_A and IN_B by four unique amino acid substitutions in the N-terminal domain: E11D, K14R, S24N, and M50I. 2019 Acta naturae Result HIV E11D;K14R;M50I;S24N 100;106;122;112 104;110;126;116 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Interestingly, G118R/E138K substitutions in the case of IN_B affected the strand transfer efficiency very slightly. 2019 Acta naturae Result HIV E138K;G118R 21;15 26;20 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Interestingly, the Q148K/G140S double substitution reduced the IN_ CRF activity more significantly than G118R/E138K did. 2019 Acta naturae Result HIV E138K;G118R;G140S;Q148K 110;104;25;19 115;109;30;24 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Introduction of Q148K/G140S resistance mutations detected in other HIV-1 subtypes also led to the emergence of IN_CRF resistance. 2019 Acta naturae Result HIV G140S;Q148K 22;16 27;21 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. It should be noted that IN_A bearing G118R/E138K mutations exhibited almost no drop in sensitivity to raltegravir. 2019 Acta naturae Result HIV E138K;G118R 43;37 48;42 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Preparation of the cDNA encoding IN_CRF and its consecutive cloning allowed us to obtain the pET-15b_IN_CRF* vector, which was then subjected to site-directed mutagenesis to introduce the I32V and I259V substitutions and to obtain the pET-15b_IN_CRF expression vector coding for a consensus IN sequence. 2019 Acta naturae Result HIV I259V;I32V 197;188 202;192 IN 291 293 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Similarly to IN_A, the Q148K/G140S and G118R/E138K substitutions significantly reduced the efficiency of strand transfer catalyzed by IN_CRF (Table 2). 2019 Acta naturae Result HIV E138K;G118R;G140S;Q148K;E138K;G118R;G140S;Q148K 46;40;30;24;45;39;29;23 51;45;35;29;50;44;34;28 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The decrease was slightly stronger in the case of G118R/E138K than for the Q148K/G140S mutation: 4.6-fold versus 3.7-fold, respectively. 2019 Acta naturae Result HIV E138K;G118R;G140S;Q148K 56;50;81;75 61;55;86;80 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The G118R and E138K substitutions resulting in reduced IN sensitivity to dolutegravir were also selected . 2019 Acta naturae Result HIV E138K;G118R 14;4 19;9 IN 55 57 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The G118R/E138K mutations also reduced the sensitivity of IN_CRF to raltegravir but not substantially (FC = 7, Table 2). 2019 Acta naturae Result HIV E138K;G118R 10;4 15;9 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The latter three substitutions are synonymous: D3E, R20K, and V31I. 2019 Acta naturae Result HIV D3E;R20K;V31I 47;52;62 50;56;66 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The mutation L74I specific to IN_A was found only in 4% of the sequences of CRF63_02A1 IN. 2019 Acta naturae Result HIV L74I 13 17 IN 87 89 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The Q148K/G140S substitutions did not change the pattern of the reaction products when compared to the initial IN_CRF. 2019 Acta naturae Result HIV G140S;Q148K 10;4 15;9 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The strong negative effect of these substitutions in both IN_CRF and IN_A is obviously related to the natural polymorphism S119P. 2019 Acta naturae Result HIV S119P 123 128 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. There are two substitutions, S24N and M50I, in the structure of IN_CRF, which seem to be of greatest interest. 2019 Acta naturae Result HIV M50I;S24N 38;29 42;33 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Therefore, IN_CRF protein variants containing Q148K/G140S and G118R/E138K double substitutions were prepared. 2019 Acta naturae Result HIV E138K;G118R;G140S;Q148K 68;62;52;46 73;67;57;51 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. We also studied the sensitivity of IN_CRF and its Q148K/G140S and G118R/E138K mutants to inhibition by raltegravir, the drug used for treatment of HIV-infected patients in the Russian Federation. 2019 Acta naturae Result HIV E138K;G118R;G140S;Q148K;E138K;G118R;G140S;Q148K 73;67;57;51;72;66;56;50 78;72;62;56;77;71;61;55 HIV infections 147 159 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. We assume that it is the rigid conformation of the active center within IN_CRF and IN_A bearing the G118R/E138K double mutation that limits their ability to bind to the target DNA, thus resulting in a sharp decrease in the number of strand transfer products for the G118R/E138K mutants. 2019 Acta naturae Result HIV E138K;E138K;G118R;G118R 106;272;100;266 111;277;105;271 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. We chose the primary mutation Q148K and the secondary compensatory mutation G140S causing IN resistance to raltegravir and elvitegravir . 2019 Acta naturae Result HIV G140S;Q148K 76;30 81;35 IN 90 92 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. We had previously revealed a decline in the catalytic activity of IN_A in the 3'-processing reaction resulting from the Q148K/G140S and G118R/E138K mutations, but this decline was the same for both double mutations (3.8-fold) . 2019 Acta naturae Result HIV E138K;G118R;G140S;Q148K 142;136;126;120 147;141;131;125 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. Predominant combinations of mutations were 140A/S + Q148H/R and N155H + G163K/R. 2019 Revista espanola de quimioterapia Result HIV G163K;G163R;N155H;Q148H;Q148R 72;72;64;52;52 79;79;69;59;59 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. Predominant major integrase resistance mutations were N155H (35.1%), Q148H/R (15.8%) and G140A/S (14%). 2019 Revista espanola de quimioterapia Result HIV G140A;G140S;N155H;Q148H;Q148R 89;89;54;69;69 96;96;59;76;76 IN 18 27 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. A122T was detectable between days 162 and 176 at frequencies that ranged between 39 and 67% (Table 1). 2019 Nature communications Result HIV A122T 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. At day 85, E92Q was transiently associated with a G140R mutation occurring at a 45% frequency. 2019 Nature communications Result HIV E92Q;G140R 11;50 15;55 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. E92Q conferred 2.5-fold resistance to CAB, 3.6-fold resistance to RAL, 7.8-fold resistance to EVG, 1.5-fold resistance to DTG, and 2.0-fold resistance to BIC. 2019 Nature communications Result HIV E92Q 0 4 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. E92Q was also detected in vaginal fluids collected from this animal. 2019 Nature communications Result HIV E92Q 0 4 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. E92Q was seen in 100% of the virus population during the entire treatment period and the pharmacological drug tail until day 127. 2019 Nature communications Result HIV E92Q 0 4 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. In this animal, an additional Q124R substitution (frequency ranging between <20 and 100%) was seen between days 155 and 183 when CAB concentrations in plasma were already undetectable. 2019 Nature communications Result HIV Q124R 30 35 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. In treated macaque 33996, A122T was also observed at day 162 (37% frequency) when plasma CAB concentrations were closer to the limit of detection of the assay. 2019 Nature communications Result HIV A122T 26 31 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Likewise, E92G reduced the susceptibility to CAB by 3.5-fold and also to RAL (2.8-fold), EVG (3.7-fold), DTG (2.8-fold), and BIC (4.3-fold). 2019 Nature communications Result HIV E92G 10 14 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Likewise, the G118R and A122T substitutions identified in plasma sequences from macaque CH54 were also detected in rectal fluids between days 71 and 120. 2019 Nature communications Result HIV A122T;G118R 24;14 29;19 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Likewise, the replication capacity of mutants containing G140R with or without E92Q was 1.3%. 2019 Nature communications Result HIV E92Q;G140R 79;57 83;62 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Macaque 10D181 acquired the E92Q mutation at day 81. 2019 Nature communications Result HIV E92Q 28 32 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Macaque 10D181 had the E92Q substitution in viruses from rectal fluids at days 120-155 in addition to two polymorphisms at positions 41 and 133. 2019 Nature communications Result HIV E92Q 23 27 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Macaque CH54 acquired both G118R and A122T at day 57. 2019 Nature communications Result HIV A122T;G118R 37;27 42;32 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Macaque CJ92 acquired two substitutions at position 72 and 123 although these mutations were transient and only observed as mixtures (52% I72T at day 32 and 41% S123A at day 127). 2019 Nature communications Result HIV I72T;S123A 138;161 142;166 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Of all the mutations identified in vivo, E92Q, E92G, G118R, and G140R were associated with resistance to INSTI. 2019 Nature communications Result HIV E92G;E92Q;G118R;G140R 47;41;53;64 51;45;58;69 INSTI 105 110 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Overall, these findings demonstrate that G118R, G140R, and E92Q/G selected during CAB LA treatment are associated with resistance to CAB and cross-resistance to other integrase inhibitors. 2019 Nature communications Result HIV E92G;E92Q;G118R;G140R 59;59;41;48 65;65;46;53 IN 167 176 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Supplementary Table 1 shows that the only two integrase mutations identified in the two control macaques were polymorphisms I250V and I110V. 2019 Nature communications Result HIV I110V;I250V 134;124 139;129 IN 46 55 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The E92Q and E92G mutations alone reduced replication capacity to 7.5-7.7% of that seen in WT. 2019 Nature communications Result HIV E92G;E92Q 13;4 17;8 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The frequency of E92Q declined to 66% at day 134. 2019 Nature communications Result HIV E92Q 17 21 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The frequency of G118R declined to 27% at day 162 and was undetectable between days 170-176. 2019 Nature communications Result HIV G118R 17 22 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The G118R and G140R mutations conferred 345- to 1000-fold resistance to all five integrase inhibitors, either alone or in association with A122T or E92Q, respectively (Table 2). 2019 Nature communications Result HIV A122T;E92Q;G118R;G140R 139;148;4;14 144;152;9;19 IN 81 90 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The I250V and I110I changes seen in macaque 33996 were also identified in one of the untreated animals (macaque 34319, Supplementary Table 1) and are polymorphisms. 2019 Nature communications Result HIV I110I;I250V 14;4 19;9 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The only mutation identified in macaque 35451 was E92G at day 143 (100% frequency). 2019 Nature communications Result HIV E92G 50 54 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The replication capacity of mutants containing G118R alone or in combination with A122T was 2.2-2.3% of that seen in WT SHIV. 2019 Nature communications Result HIV A122T;G118R 82;47 87;52 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. A shift of 0.8 A in M46L is observed in PRS17/CA-p2 in comparison to complex with DRV. 2019 ACS omega Result HIV M46L 20 24 Capsid;PR 46;40 48;42 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Also, PR with individual mutations of M46L, G48V, and I54V in the flaps showed worse inhibition constants (Ki) for DRV and saquinavir relative to the wild-type PR. 2019 ACS omega Result HIV G48V;I54V;M46L 44;54;38 48;58;42 PR;PR 6;160 8;162 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Altered Recognition of CA-p2 P3 Arg Modulated by V82S Mutation. 2019 ACS omega Result HIV V82S 49 53 Capsid 23 25 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. As a result, the tip of the flap of PRS17-D25N moves ~4.4 A closer to 80's loop, as measured by the distance between the Calpha atoms of Ile50 and Thr80. 2019 ACS omega Result HIV D25N 42 46 PR 36 38 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Comparison of inhibitor-free PRS17-D25N with the wild-type PR open form without inhibitor (2PC0) shows that the two structures superpose with a root-mean-square deviation (RMSD) of 1.4 A for the 99 topologically equivalent Calpha atoms. 2019 ACS omega Result HIV D25N 35 39 PR;PR 29;59 31;61 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Crystal structures of inhibitor-free PRS17-D25N and wild-type PR in complex with CA-p2 substrate analogue were determined in the P3221 and P21212 space groups at 1.21 and 1.46 A resolutions, respectively. 2019 ACS omega Result HIV D25N 43 47 Capsid;PR;PR 81;37;62 83;39;64 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Curling of Flaps in PRS17-D25N. 2019 ACS omega Result HIV D25N 26 30 PR 20 22 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Due to G48V mutation inducing ~160 of rotation along the Calpha-C bond of P3 residue, the P4 Ace residue occupies a different binding pocket in PRS17 complexes to that observed in the wild-type structure. 2019 ACS omega Result HIV G48V 7 11 PR 145 147 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Due to the steric hindrance caused by G48V mutation, all three conformations of the side chain of P3 Arg in PRS17/CA-p2 dimers swing away from Val48 and interact with Arg8'. 2019 ACS omega Result HIV G48V 38 42 Capsid;PR 114;108 116;110 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Flap mutations M46L, G48V, and I54V in PRS17 are implicated in the curling of flaps observed in the inhibitor-free structure. 2019 ACS omega Result HIV G48V;I54V;M46L 21;31;15 25;35;19 PR 39 41 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. G48V Mutation of PRS17 Results in Altered Binding Position of P3 and P4 Residues of p2-NC and Addition of Two New Hydrogen Bonds. 2019 ACS omega Result HIV G48V 0 4 NC;PR 87;17 89;19 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. However, G48V together with M46L also alters the conformation of other flap residues like Phe53 as seen in PRS17/DRV complex, which may affect the inhibitor binding. 2019 ACS omega Result HIV G48V;M46L 9;28 13;32 PR 107 109 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. However, in the mutant PRS17/CA-p2 complex, the introduction of G48V mutation causes the Phe53 side chain to rotate out by more than 140 in comparison to the wild-type complex. 2019 ACS omega Result HIV G48V 64 68 Capsid;PR 29;23 31;25 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. However, the larger G48V mutation in PRS17 complexes induces shifts in P3 Thr Calpha and Cbeta atoms by ~0.7 and 1.8 A in comparison to their corresponding positions in the PR/p2-NC complex (Figure 5B). 2019 ACS omega Result HIV G48V 20 24 NC;PR;PR 179;37;173 181;39;175 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. However, the peptide bond between Ile50 and Gly51 is flipped in PRS17 structure in comparison to PRS17-D25N (Figure 2B). 2019 ACS omega Result HIV D25N 103 107 PR;PR 64;97 66;99 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In addition to the shift in Phe53, the mutation of Met46 to shorter Leu46 in PRS17-D25N also eliminates van der Waals contacts observed in the wild-type PR between Phe53 and Met46. 2019 ACS omega Result HIV D25N 83 87 PR;PR 77;153 79;155 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In both PRS17-P41/p2-NC and PRS17-P61/p2-NC complexes, the P3' Arg binds in the same pocket albeit the guanidine head of P3' Arg is tilted toward V82S mutation due to the lack of a beta-branched Cdelta atom in residue 82. 2019 ACS omega Result HIV V82S 146 150 NC;NC;PR;PR 21;41;8;28 23;43;10;30 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In PRS17, the Val side chain of G48V mutation produces steric hindrance and prevents the formation of the interaction between Phe53 and P3 Arg observed in the wild-type PR complex. 2019 ACS omega Result HIV G48V 32 36 PR;PR 3;169 5;171 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In PRS17/DRV complex, M46L and G48V mutations are shown to synergistically alter the conformation of Phe53 by steric hindrance underlying the relationship between the three residues. 2019 ACS omega Result HIV G48V;M46L 31;22 35;26 PR 3 5 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In this new conformation, the P3 Thr side chain forms several van der Waals contacts with the side chains of G48V mutation and Arg8' in PRS17 complexes. 2019 ACS omega Result HIV G48V 109 113 PR 136 138 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Mutation V82S Mediates Enhanced Binding of P3' Arg in p2-NC. 2019 ACS omega Result HIV V82S 9 13 NC 57 59 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. On the other hand, the flap curling also increases by ~1.4 A, the distance between the flap tip of PRS17-D25N and the active site, since the distance between the Calpha atoms of Asp25 and Ile50 increased from 17.6 A in the wild-type structure to 19.0 A in PRS17-D25N. 2019 ACS omega Result HIV D25N;D25N 105;262 109;266 Asp;PR;PR 178;99;256 181;101;258 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Similar to PRS17-D25N, the flap curling in PRS17 starts with ~176 change in phi angle of G48V and ends at Gly52. 2019 ACS omega Result HIV G48V;D25N 90;17 94;21 PR;PR 11;43 13;45 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Similar to the wild-type PR, the flaps of PRS17-D25N are in an open conformation. 2019 ACS omega Result HIV D25N 48 52 PR;PR 25;42 27;44 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Similar to V82S mutation in PRS17, V82A mutation is also expected to expand the binding site for P3 Arg, but other larger and beta-branched mutations may block the access to this site. 2019 ACS omega Result HIV V82A;V82S 35;11 39;15 PR 28 30 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Similar to V82S, V82A mutation opens up the S3 site for substrate recognition. 2019 ACS omega Result HIV V82A;V82S 17;11 21;15 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The Calpha atoms of residues Thr80, Pro81, and V82S are shifted by 1.1, 1.3, and 0.7 A, respectively, for the PRS17-P41/p2-NC complex and 1.3, 1.4, and 0.6 A for the PRS17-P61/p2-NC complex from the corresponding Calpha atoms in the PR/p2-NC complex (Figure 5A). 2019 ACS omega Result HIV V82S 47 51 NC;NC;NC;PR;PR;PR 123;179;239;110;166;233 125;181;241;112;168;235 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The co-occurrence of flap mutations like G48V that block P3 substrate-binding site and large substitutions at residue 82 like V82F, V82L, and V82I that block the alternate P3 binding site are expected to be detrimental to PR activity. 2019 ACS omega Result HIV G48V;V82F;V82I;V82L 41;126;142;132 45;130;146;136 PR 222 224 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The current crystal structure of PRS17-D25N at 1.21 A is the highest-resolution HIV PR structure in the open conformation available to date. 2019 ACS omega Result HIV D25N 39 43 PR;PR 33;84 35;86 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The effect of Val82 mutation appears to be two-fold; it alters the resistance profile of PR inhibitors and regulates the access to Arg8/8' in the recognition of substrate P3 residue in response to resistance flap mutations like G48V that hinder substrate recognition. 2019 ACS omega Result HIV G48V 228 232 PR 89 91 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The G48V mutation further contributes to more than 1.5 A shift in the position of terminal P5' NH2, which loses van der Waals contact with Phe53 but retains the hydrogen bond with the carbonyl of Leu46. 2019 ACS omega Result HIV G48V 4 8 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The inhibitor-free PRS17-D25N structure has one monomer in the asymmetric unit with residues numbered 1-99, while PR/CA-p2, PRS17-P41/p2-NC, and PRS17-P61/p2-NC complexes contain a dimer of subunits numbered 1-99 and 1'-99' in the asymmetric unit. 2019 ACS omega Result HIV D25N 25 29 NC;NC;Capsid;PR;PR;PR;PR 137;158;117;19;114;124;145 139;160;119;21;116;126;147 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The introduction of Val48 side chain in PRS17-D25N results in ~1.1 A shift of Phe53 side chain's benzene ring when compared to that of the wild-type PR. 2019 ACS omega Result HIV D25N 46 50 PR;PR 40;149 42;151 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The larger side chain of the G48V mutation in the S2 pocket may play an important role in the better inhibition constant (Ki = 11 nM) of APV for PRS17. 2019 ACS omega Result HIV G48V 29 33 PR 145 147 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The loss of beta-branched side chain in V82S mutation results in a significant shift of 80's loop residues toward Arg8 in PRS17 complexes. 2019 ACS omega Result HIV V82S 40 44 PR 122 124 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The major conformation of P3 Arg in the PRV82A/CA-p2 complex forms van der Waals contact with Phe53 in the second strand of the flaps similar to the PR/CA-p2 complex, while the carbonyl of P4' Nle of the minor conformation related by 180 occupies the P3 Arg site observed in the PRS17/CA-p2 complex (Figure 4E). 2019 ACS omega Result HIV V82A 42 46 Capsid;Capsid;Capsid;PR;PR;PR 47;152;286;40;149;280 49;154;288;42;151;282 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The major effect appears to be the mutation to a smaller side chain at Val82, since PR bearing single mutation V82A (PRV82A) displays almost identical inhibition kinetics for CA-p2 (Ki = 24 nM) and p2-NC (Ki = 530 nM) as those measured for PRS17. 2019 ACS omega Result HIV V82A 111 115 NC;Capsid;PR;PR;PR 201;175;84;117;240 203;177;86;119;242 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The Nepsilon2 atom of the guanidine head of P3' Arg in PRS17 complexes is shifted by 1.0 A (PRS17-P41/p2-NC) and 1.2 A (PRS17-P61/p2-NC) toward V82S in comparison to the PR/p2-NC complex. 2019 ACS omega Result HIV V82S 144 148 NC;NC;NC;PR;PR;PR;PR 105;133;176;55;92;120;170 107;135;178;57;94;122;172 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The overall structure of PRS17-D25N is very similar to the inhibitor-free PRS17 structure with an RMSD of 0.18 A for 99 equivalent Calpha atoms. 2019 ACS omega Result HIV D25N 31 35 PR;PR 25;74 27;76 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The P4 residue in the PRS17 cannot occupy the same pocket as in the wild-type structure due to steric hindrance from G48V mutation and the loss of interaction with Val82' as a result of V82'S mutation. 2019 ACS omega Result HIV G48V 117 121 PR 22 24 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The reorganization of the hinge loop by mutations E35D, M36I, and S37D that breaks the ion pair anchoring the flaps and thereby increases the flap flexibility as described in the previously determined complex of PRS17 with darunavir (DRV) is also observed in the current substrate analogue complexes. 2019 ACS omega Result HIV E35D;M36I;S37D 50;56;66 54;60;70 PR 212 214 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The serine side chain of V82S mutation in both monomers of PRS17/DRV has two alternate conformations mimicking the two beta-branches of valine, while in the substrate analogue complexes, it has a single conformation that points away from Arg8 to accommodate the substrate residues. 2019 ACS omega Result HIV V82S 25 29 PR 59 61 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The three mutations M46L, G48V, and I54V in PRS17 flaps act to curl the tip of flaps (Figure 2A). 2019 ACS omega Result HIV G48V;I54V;M46L 26;36;20 30;40;24 PR 44 46 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The twist in the flap starts at G48V of PRS17-D25N with a drastic change in phi angle by ~172 in comparison with Gly48 of the wild-type PR. 2019 ACS omega Result HIV G48V;D25N 32;46 36;50 PR;PR 40;137 42;139 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Thermodynamic integration and molecular mechanics Poisson-Boltzmann surface area studies have shown that the larger side chain introduced by G48V mutation strengthens van der Waals interactions with APV. 2019 ACS omega Result HIV G48V 141 145 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. This curling of flap tips propagates from G48V up to Gly52 in PRS17-D25N. 2019 ACS omega Result HIV G48V;D25N 42;68 46;72 PR 62 64 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. This distance is 14.5 A for the wild-type PR, while it is 10.1 A for the PRS17-D25N structure. 2019 ACS omega Result HIV D25N 79 83 PR;PR 42;73 44;75 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. This flipped peptide bond enables residue Ile50 at the flap tip of PRS17 to move closer to the 80's loop residue Thr81 (~8.8 A) than in PRS17-D25N (10.1 A), while the distance between catalytic Asp25/Asn25 and the flap tip Ile50 remains more or less the same between the two structures (18.7 A for PRS17 and 19.0 A for PRS17-D25N). 2019 ACS omega Result HIV D25N;D25N 142;325 146;329 Asp;PR;PR;PR;PR 194;67;136;298;319 197;69;138;300;321 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Through changes in the flap strands including the position of M46L or G48V in combination with the change in rotamer for side chains of Leu46, Val48, and Phe53, PRS17 binds substrate analogues as tightly as it binds DRV (Ki = 50 nM). 2019 ACS omega Result HIV G48V;M46L 70;62 74;66 PR 161 163 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Thus, despite large shifts in P3 and P4 residues induced by the G48V mutation, PRS17 accommodates the substrate residues in alternate sites and gains two hydrogen bond interactions. 2019 ACS omega Result HIV G48V 64 68 PR 79 81 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Thus, identical curling of flaps in two independently determined structures of PRS17-D25N and PRS17 strongly implies that the conformational changes are due to the three mutations M46L, G48V, and I54V in the flaps of PRS17 and contribute to the altered kinetic characteristics of PRS17. 2019 ACS omega Result HIV G48V;I54V;M46L;D25N 186;196;180;85 190;200;184;89 PR;PR;PR;PR 79;94;217;280 81;96;219;282 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Thus, in the PRS17/CA-p2 complex, the G48V flap mutation in conjunction with the V82S mutation facilitates the binding of the side chain of P3 Arg in the new site. 2019 ACS omega Result HIV G48V;V82S 38;81 42;85 Capsid;PR 19;13 21;15 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Thus, the analysis of the three PRS17 substrate analogue complexes indicates that the loss of beta-branched side chain by V82S mutation initiates the shifting of 80's loop and reshapes the S3/S3' subsite for enhanced binding and interactions with P3/P3'. 2019 ACS omega Result HIV V82S 122 126 PR 32 34 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Amongst the genetic mutations resistant to NNRTIs, G190S mutation was the highest (51.2%), K101HQ mutation was 39.5%, and Y181I mutation was 34.9% (Table 3). 2019 Infection and drug resistance Result HIV G190S;K101H;K101Q;Y181I 51;91;91;122 56;97;97;127 NNRTI 43 49 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. In genetic mutations to NRTIs, M184V was the most common ARV-resistant pattern (88.4%). 2019 Infection and drug resistance Result HIV M184V;M184V 32;31 37;36 NRTI 24 29 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. In genetic mutations to PIs, M36I and K20R mutations made up 9.3% (Table 5). 2019 Infection and drug resistance Result HIV K20R;M36I 38;29 42;33 PI 24 27 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. In thymidine analogue mutations (TAMs), K70R mutation was the most common (37.2%). 2019 Infection and drug resistance Result HIV K70R 40 44 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. The proportions of D67N and T215F mutations were 27.9% and 27.9%, respectively (Table 4). 2019 Infection and drug resistance Result HIV D67N;T215F 19;28 23;33 31257432 Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda. The most prevalent NNRTI mutations were K103N (39.2%), Y181C (19.6%) and G190A (15.5%) (Figure 3). 2019 The Journal of antimicrobial chemotherapy Result HIV G190A;K103N;Y181C 73;40;55 78;45;60 NNRTI 19 24 31257432 Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda. The most prevalent NRTI mutations were M184V/I (53.6%), K65R (17.5%) and thymidine analogue mutations (TAMs) were present in 21.6% of VF cases. 2019 The Journal of antimicrobial chemotherapy Result HIV K65R;M184I;M184V 56;39;39 60;46;46 NRTI 19 23 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. Although none had known PI- or INSTI-associated DRMs, several other mutations were identified in the protease and integrase regions (A9P, E15K, A42E/T, K258 N, N278S/D, Y336C, G345A/S, K462R, and M532R/L) in two or three samples each. 2019 BMC infectious diseases Result HIV A42E;A42T;A9P;E15K;G345A;G345S;K258N;K462R;M532L;M532R;N278D;N278S;Y336C 144;144;133;138;176;176;152;185;196;196;160;160;169 150;150;136;142;183;183;158;190;203;203;167;167;174 IN;PR;INSTI;PI 114;101;31;24 123;109;36;26 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. In the C-terminal of p17, 14 (87.5%) of the 16 patients displayed the R4S mutation. 2019 BMC infectious diseases Result HIV R4S 70 73 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. In the Gag-p6 region, A5G/E/P/P5S/A/R5A and K6S/P6A/S6K/E6K/V6E mutations were displayed in seven and five samples, respectively. 2019 BMC infectious diseases Result HIV A5E;A5G;A5P;E6K;K6S;P5A;P5S;P6A;R5A;S6K;V6E 22;22;22;56;44;30;30;48;36;52;60 29;29;29;59;47;33;33;51;39;55;63 Gag;Gag;Gag 7;11;48 10;13;50 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. K65R was found in 10 (35.7%) subjects. 2019 BMC infectious diseases Result HIV K65R 0 4 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. K65R was found in eight (50%) patients and TAM-2 in five patients. 2019 BMC infectious diseases Result HIV K65R 0 4 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. Mutations were also identified in the vif (N36K/S n = 4; G101S/D n = 4, V31I n = 3, K33R, R34K, K63R, R92G, G101D n = 2) and in the nef gene (A15E/S n = 3, L20I/A/R n = 3; W5R/Q, K7N, C8S, V11P/G, R19A/P, D24A/G, K105 N/T, K118E/R n = 2). 2019 BMC infectious diseases Result HIV A15E;A15S;C8S;D24A;D24G;G101D;G101D;G101S;K105N;K105T;K118E;K118R;K33R;K63R;K7N;L20A;L20I;L20R;N36K;N36S;R19A;R19P;R34K;R92G;V11G;V11P;V31I;W5Q;W5R 142;142;184;205;205;57;108;57;213;213;223;223;84;96;179;156;156;156;43;43;197;197;90;102;189;189;72;172;172 148;148;187;211;211;64;113;64;221;221;230;230;88;100;182;164;164;164;49;50;203;203;94;106;195;195;76;177;177 Nef;Vif 132;38 135;41 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. No K65R was found in this group. 2019 BMC infectious diseases Result HIV K65R 3 7 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. No significant difference was found in viral load at month 6 for patients failing TDF with or without K65R. 2019 BMC infectious diseases Result HIV K65R 102 106 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. On the other hand, only one patient had a mutation (T375 M) in the p2/NC gag cleavage site. 2019 BMC infectious diseases Result HIV T375M 52 58 Gag;NC 73;70 76;72 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. The predominant mutations were M184V16 (70%) and K103N 15 (65%). 2019 Sexually transmitted infections Result HIV K103N 49 54 31269034 Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study. Irrespective of the scenario, the prevalence of the NNRTI-associated (class), M184V and K65R (signature) mutations was comparable (~80%) in individuals with acquired resistance and virological non-suppression, by 2030 (Fig 3C). 2019 PloS one Result HIV K65R;M184V 88;78 92;83 NNRTI 52 57 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Also visible in the maps of differences in Calpha-Calpha distances between KY and KY(V89L) is the dramatic displacement of the chain B flap elbow (residues 38-39 and 42-43). 2019 Biochemistry Result HIV V89L 85 89 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Although KY(V89L) and KY(DM) sample an identical 71-89 distance distribution, only the chain A flap of KY(V89L) open up slightly as indicated by the increased I50-I84' distance (Figure 5B). 2019 Biochemistry Result HIV V89L;V89L 12;106 16;110 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Although the KY variant also samples larger values of phib, its distribution is altered from that of KY(V89L) and does not correspond to a loss of van der Waals contacts at G27' or A28'. 2019 Biochemistry Result HIV V89L 104 108 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. As noted above, however, the presence of the L90M mutation in the NL4-3 background is clearly associated with modulating the dynamics of the flaps. 2019 Biochemistry Result HIV L90M 45 49 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. As was the case with the wild-type protease, our binding assay was not sensitive enough to accurately measure Ki for DRV binding when the L89V and L90M mutations were introduced, whether individually or together. 2019 Biochemistry Result HIV L89V;L90M 138;147 142;151 PR 35 43 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. By contrast, the distribution about phia in the KY(DM) and KY(M90L) variants was shifted to a slightly higher mean angle, corresponding to more frequent observation of a hydrogen bond between DRV and D25. 2019 Biochemistry Result HIV M90L 62 66 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. By contrast, the JSD between KY and KY(M90L) (Figure 6E) or between KY and KY(DM) (Figure 6F) is greater within the alpha-helix and more muted elsewhere in the protease, like the 70's loop and flap elbows. 2019 Biochemistry Result HIV M90L 39 43 PR 160 168 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Compared with the NL4-3 wild-type protease, DRV exhibits greater fluctuations in all of the resistant variants, with the KY(V89L) variant showing the largest RMSF among those studied here (Figure 3). 2019 Biochemistry Result HIV V89L 124 128 PR 34 42 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Consistent with the per-residue Calpha RMSF profiles of the KY variants, NL4-3(L89V), NL43(L90M), and NL4-3(DM) all show a significant increase in flap fluctuations compared to the NL4-3 wild-type. 2019 Biochemistry Result HIV L89V;L90M 79;91 83;95 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Contrary to previous reports, and consistent with our previous observations, no changes in the position of D25/D25' were observed due to the presence of the L90M mutation alone. 2019 Biochemistry Result HIV L90M 157 161 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Even in the relatively high entropy phid states for KY(V89L) and KY(M90L), the sampling between rotamers is not symmetric (the per-dihedral entropy, is reported in Table S3), with the rotameric state near -82 both less populated and relatively lopsided compared to its counterpart at larger angles. 2019 Biochemistry Result HIV M90L;V89L 68;55 72;59 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Examining the differences in mean intra-protein Calpha-Calpha distances between KY and KY(V89L) emphasizes that the displacement observed in Figures 6A and 6B broadly involve secondary structure elements of the protease, with the 70's beta-sheet and the alpha-helix moving away from one another in the KY(V89L) variant (Figure S12). 2019 Biochemistry Result HIV V89L;V89L 90;305 94;309 PR 211 219 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. For all of the HIV-1 protease variants, with the exception of KY(V89L), the Michaelis-Menten constant, KM, was unchanged, indicating that the affinity for the substrate is similar among the highly mutated KY variants and the NL4-3 enzyme. 2019 Biochemistry Result HIV V89L 65 69 PR 21 29 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. For KY(V89L), the most profound consequence due to the changes in phib is that DRV loses van der Waals contacts with G27' and A28', residing in the S1' and S2' subsites, respectively (Figure S16). 2019 Biochemistry Result HIV V89L 7 11 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. For the KY(V89L) variant, kinetic measurements were beyond the sensitivity of our fluorescence assay, indicating a significant decrease in catalytic efficiency. 2019 Biochemistry Result HIV V89L 11 15 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. For the NL4-3(L90M) variant, the catalytic efficiency is dramatically reduced by 428-fold relative to wild-type (Table S2) as a result of 2- and 214-fold reductions in KM and kcat, respectively. 2019 Biochemistry Result HIV L90M 14 18 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. From examining the computed JSD between KY and KY(V89L) for the all dihedral angles, the effects of the L89V mutation are clearly visible throughout the protease, including the alpha-helix, 70's loop and flap elbows (Figure 6D). 2019 Biochemistry Result HIV L89V;V89L 104;50 108;54 PR 153 161 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In both the NL4-3 WT background and that of the highly mutated KY resistant variant, the L90M mutation reduces catalytic efficiency while the co-occurrence of L89V acts as a buffer on this effect and restores catalytic efficiency. 2019 Biochemistry Result HIV L89V;L90M 159;89 163;93 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In complex with KY(M90L), the water-mediated hydrogen bond with the sulfonamide moiety of DRV is reduced to 64%. 2019 Biochemistry Result HIV M90L 19 23 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In KY(V89L), the most resistant of the variants, the water-mediated hydrogen bond between the P2' sulfonamide oxygen and backbone amide group of I50' is not formed, while the water-mediated bond between the P2 bis-THF and the backbone amide group of I50 is maintained at 58% (Figure 7). 2019 Biochemistry Result HIV V89L 6 10 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In NL4-3(DM), bearing both L89V and L90M, DRV exhibits little correlation with the floor of the active site (residues 25-30/25'-30') while maintaining moderate correlation with the chain B flap tip. 2019 Biochemistry Result HIV L89V;L90M 27;36 31;40 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In order to study how the interdependence of the L89V and L90M mutations helps HIV-1 protease evade DRV inhibition, the patient-derived KY strain was expressed. 2019 Biochemistry Result HIV L89V;L90M 49;58 53;62 PR 85 93 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In the KY variant, this partial distribution for the DRV phib dihedral angle has a single peak that is intermediate to those of KY(V89L), centered near -3pi/8 radians. 2019 Biochemistry Result HIV V89L 131 135 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In using the JSD of dihedral angle distributions to compare KY and KY(M90L) particularly, alterations are detected at residues L24/L24' in the active site, which may account for the observed 3-fold difference in Ki between these two variants. 2019 Biochemistry Result HIV M90L 70 74 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Indeed, the distributions of phib sampled by the KY(M90L) and KY(DM) variants are similar, consistent with the observation that they have the same Ki (Table 1). 2019 Biochemistry Result HIV M90L 52 56 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Indeed, the KY variant protease binds DRV about 3.5 times more tightly than would be expected under the assumption of additivity for binding free energies: using the definition from above for excess change in the relative free energy of inhibitor binding, The inhibition assays suggest that the L90M mutation provides virtually all of the resistance while both the catalytic assays and the time-course p55 cleavage assay suggest a compensatory role for the L89V mutation, specifically selected for by the KY variant to restore catalytic efficiency. 2019 Biochemistry Result HIV L89V;L90M 458;296 462;300 PR 23 31 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Introducing the L90M mutation to the NL4-3 wild-type protease causes a significant enhancement in the fluctuations at flap residues 48-49 and 52'. 2019 Biochemistry Result HIV L90M 16 20 PR 53 61 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. KY samples an intermediate distance between KY(V89L) and the wild-type. 2019 Biochemistry Result HIV V89L 47 51 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. KY(M90L) samples the smallest 71'-89' distance compared to the KY variants, while the NL4-3 wild-type samples the smallest 71'-89' distance overall. 2019 Biochemistry Result HIV M90L 3 7 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. NL4-3(L90M) was solved in the P21 space group with two protease homodimers in the asymmetric unit. 2019 Biochemistry Result HIV L90M 6 10 PR 55 63 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Note that the increase in RMSF for KY(V89L) is most pronounced within the P2' sulfonamide moiety, whereas for KY(DM) a greater increase is observed within the P2 bis-tetrahydrofuran moiety (Figure 3). 2019 Biochemistry Result HIV V89L 38 42 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. On the B chain, the KY(V89L) and KY(DM) variants again show the greatest displacement compared with the remaining KY variants and the wild-type (Figure 6B). 2019 Biochemistry Result HIV V89L 23 27 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Only in the KY(V89L) variant, is there substantial density in at larger separations and phib near -pi/4 radians. 2019 Biochemistry Result HIV V89L 15 19 PI 100 102 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Relative to the NL4-3 wild-type strain, KY has 24 amino acid substitutions, including the L89V and L90M resistance mutations (Figure S2). 2019 Biochemistry Result HIV L89V;L90M 90;99 94;103 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Since the activity of the KY(V89L) variant could not be determined through traditional kinetics assays, which use a single cleavage site (MACA), a time-course gel assay that monitors the cleavage of full-length Gag polyprotein (p55) over time was used. 2019 Biochemistry Result HIV V89L 29 33 Gag 211 214 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Taken together, these results suggest that the L89V mutation acts to "rescue" the enzymatic function of the protease in the presence of the severe catalytic penalty imposed by the L90M resistance mutation. 2019 Biochemistry Result HIV L89V;L90M 47;180 51;184 PR 108 116 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The catalytic efficiency of the NL4-3(L89V) variant was reduced 57fold, relative to WT, with KM increasing 1.5-fold and kcat decreasing by 96-fold. 2019 Biochemistry Result HIV L89V 38 42 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The changes in binding free energy and mean DRV-protease vdW energy are highly correlated with one another (Figure S17), with KY(V89L) having the least favorable mean vdW interactions among the studied variants (Table 1). 2019 Biochemistry Result HIV V89L 129 133 PR 48 56 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The cleavage of p55 in KY and KV(V89L) proceeds in the same order as it does in WT protease. 2019 Biochemistry Result HIV V89L 33 37 PR 83 91 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The distribution about phia was similar in the KY and KY(V89L) variants (Figure 8), corresponding to similar hydrogen bonding frequencies between the DRV hydroxyl group and the catalytic D25 residue (Figure 7). 2019 Biochemistry Result HIV V89L 57 61 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The effect of the L90M mutation on flap dynamics offers a more plausible explanation for the enzymatic penalties discussed above compared with previous reports, indicating that the longer methionine side chain perturbs the catalytic aspartate residues. 2019 Biochemistry Result HIV L90M 18 22 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The expanded catalytic site in the KY(V89L) variant, with the inter-Calpha distance between residues I50 and I84' centered around 11.75A, is associated with a shifted and broadened distribution of the phib dihedral angle compared with the other variants (Figures 9A and S19). 2019 Biochemistry Result HIV V89L 38 42 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The interdependency of L89V and L90M for binding and cleavage. 2019 Biochemistry Result HIV L89V;L90M 23;32 27;36 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The introduction of the L90M mutation in NL43(L90M) shows a moderate anticorrelation between the inhibitor and both alpha-helices while maintaining moderate correlation with the chain A flap tip. 2019 Biochemistry Result HIV L90M;L90M 24;46 28;50 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The KY(DM) revertant variant, containing wild-type leucine amino acids at residues 89 and 90, also exhibits diminished catalytic efficiency compared with the NL4-3 wild-type protease, yet is more active than either of the KY(V89L) or KY(M90L) variants (Table 1). 2019 Biochemistry Result HIV M90L;V89L 237;225 241;229 PR 174 182 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The KY(M90L) variant, like KY and KY(V89L), exhibits a diminished turnover number, in this case kcat is observed to decrease by 27-fold relative to NL4-3. 2019 Biochemistry Result HIV M90L;V89L 7;37 11;41 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The KY(V89L) and KY(DM) variants, both of which have the wild-type leucine at residue 89, show the greatest displacement among the KY variants (Figure 6A). 2019 Biochemistry Result HIV V89L 7 11 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The L89V and L90M mutations were introduced in the NL4-3 wild-type background to study their enzymatic effects independent of the remaining 22 mutations that are present in the KY variant. 2019 Biochemistry Result HIV L89V;L90M 4;13 8;17 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The L89V mutation, located in the alpha-helix, induces structural changes at residue I71 (Figure 6D). 2019 Biochemistry Result HIV L89V 4 8 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The P2' aniline group was observed to interconvert between these two states in the KY(V89L) and KY(M90L) variants, indicating a lowered free energy barrier for these systems compared with KY, KY(DM) and the NL4-3 wild-type. 2019 Biochemistry Result HIV M90L;V89L 99;86 103;90 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The presence of the L89V mutation in the NL4-3 wild-type background leads to a loss in correlation between DRV and both flap tips, while maintaining high correlation with the S2 subsite where the bis-THF moiety binds (Figure S11). 2019 Biochemistry Result HIV L89V 20 24 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The radial distribution function for the Calpha atoms of residues I50 and I84' is bimodal for the KY(V89L) variant, with one maximum at 10.25A and another at 11.75A. 2019 Biochemistry Result HIV V89L 101 105 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The steric interactions between the bulky side chains of residues I71 and L89 may be responsible for the differences observed in the dihedral angle distributions in KY(V89L) and KY(DM). 2019 Biochemistry Result HIV V89L 168 172 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. The widest range of phib rotameric states and the largest angles are sampled by the highly resistant KY(V89L) variant. 2019 Biochemistry Result HIV V89L 104 108 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. These findings are directly relevant to the increased flap tip fluctuations and expansion of the catalytic site that are present in the KY(V89L) variant, mutations at residue 89, located in the hydrophobic core of the protein, have previously been reported to perturb hydrophobic sliding, thereby altering the flap motion. 2019 Biochemistry Result HIV V89L 139 143 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. These observations can help explain the molecular mechanism by which the KY(V89L) variant loses the water-mediated hydrogen bond between the P2' sulfonamide moiety and residue I50'. 2019 Biochemistry Result HIV V89L 76 80 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. This broadness in the angular distribution of phib is associated with the weakened DRV binding measured for KY(V89L). 2019 Biochemistry Result HIV V89L 111 115 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. This enhancement is not observed for the NL4-3(L89V) or NL4-3(DM) variants. 2019 Biochemistry Result HIV L89V 47 51 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. This gel assay indicates that compared to the KY protease, full-length p55 cleavage by the KY(V89L) protease is approximately 3-times slower compared to KY (Figure S4), representing a fitness penalty for the virus. 2019 Biochemistry Result HIV V89L 94 98 PR;PR 49;100 57;108 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. This loss of favorable van der Waals contacts contributes to the anticorrelation noted above between the motions of DRV and those of the G27' and A28' residues in the KY(V89L) variant (Figure 4). 2019 Biochemistry Result HIV V89L 170 174 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. This observation suggests that the L90M mutation is responsible for altering fluctuations at the flaps, while residue 89 negates those effects by acting on the 70's beta-sheet. 2019 Biochemistry Result HIV L90M 35 39 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Three additional variants of KY were also expressed and purified, reverting the two sites of interest individually and together: KY(V89L), containing the L90M mutation but not L89V, KY(M90L), containing the L89V mutation but not L90M, and KY(DM) where both residues 89 and 90 were reverted to the NL4-3 sequence 89L and 90L. 2019 Biochemistry Result HIV L89V;L89V;L90M;L90M;M90L;V89L 176;207;154;229;185;132 180;211;158;233;189;136 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Three variants were expressed and purified, NL4-3(L89V), NL4-3(L90M) and NL43(DM) containing both L89V and L90M. 2019 Biochemistry Result HIV L89V;L90M;L89V;L90M 98;107;50;63 102;111;54;67 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. To characterize how the L89V and L90M mutations affect structural changes in the KY protease variants, the Jensen-Shannon divergence (JSD) was utilized to compare the equilibrium conformational ensemble of KY against that of KY(V89L), KY(M90L), and KY(DM) (see Materials and Methods). 2019 Biochemistry Result HIV L89V;L90M;M90L;V89L 24;33;238;228 28;37;242;232 PR 84 92 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. To determine if the effects of the L89V and L90M mutations on flap dynamics are independent of the remaining 22 mutations in KY, MD simulations were carried out for DRV bound to NL4-3(L89V), NL4-3(L90M), and NL4-3(DM). 2019 Biochemistry Result HIV L89V;L90M;L89V;L90M 35;44;184;197 39;48;188;201 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. To further elucidate the non-additive nature of the L89V and L90M mutations and understand their co-occurrence, the inhibition constant, Ki, of DRV against several HIV-1 protease variants was determined using an optimized substrate (Table 1). 2019 Biochemistry Result HIV L89V;L90M 52;61 56;65 PR 170 178 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Under expanded conditions (with the inter-Calpha distance between residues I50 and I84' greater than 12A), KY(M90L) and KY(DM) both sample a single peak centered near dihedral angles of -pi/2 radians, while KY(V89L) samples two peaks: one at -pi/2 radians and another at -pi/4 radians. 2019 Biochemistry Result HIV M90L;V89L 110;210 114;214 PI;PI;PI 187;243;272 189;245;274 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Unique to the NL4-3(L90M) mutant is a drastic increase in fluctuation at residues 48-49 of the chain A flap and residue 52' of the chain B flap (Figure S8). 2019 Biochemistry Result HIV L90M 20 24 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. When both L89V and L90M mutations are introduced to the wild-type sequence, however, the penalty in catalytic efficiency is attenuated compared with either mutation on its own: the double mutant exhibits a reduction of 2.5- and 12-fold, respectively in KM and kcat. 2019 Biochemistry Result HIV L89V;L90M 10;19 14;23 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. While epistasis between the L89V and L90M mutations in HIV-1 protease has been previously reported, the changes in enzymatic structure, dynamics, and function that underlie this specific non-additivity are not understood. 2019 Biochemistry Result HIV L89V;L90M 28;37 32;41 PR 61 69 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. While the darunavir-protease cross-correlations observed for residues in the S2' subsite (residues G27', A28' and D29') are weakly negative for KY(M90L) and KY(DM) and weakly positive for NL4-3 and KY, those of KY(V89L) exhibit a moderate anticorrelation (Figure 4F). 2019 Biochemistry Result HIV M90L;V89L 147;214 151;218 PR 20 28 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. While the DRV-bound wild-type protease does not sample this expanded state around 11.75A, all of the KY variants do so to differing degrees, with KY(V89L) showing the greatest density by far. 2019 Biochemistry Result HIV V89L 149 153 PR 30 38 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Wild-type protease and NL4-3(L89V) were solved in the same P212121 space group with one protease homodimer in the asymmetric unit. 2019 Biochemistry Result HIV L89V 29 33 PR;PR 10;88 18;96 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. A simple molecular docking diagram showing the interaction of ATV with both the wildtype and the E35D G S variant is shown in Figure 5. 2019 Journal of enzyme inhibition and medicinal chemistry Result HIV E35D 97 101 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Log vitality values are shown in Figure 3 for the E35D G S mutant protease with the corresponding inhibitor using the wild type as a reference enzyme. 2019 Journal of enzyme inhibition and medicinal chemistry Result HIV E35D 50 54 PR 66 74 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The E35D G S mutant showed low vitality values for APV and RTV displaying log vitality values of 0.36 and 0.30, respectively. 2019 Journal of enzyme inhibition and medicinal chemistry Result HIV E35D 4 8 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The kinetic Michaelis constant was found to be 128.6 +- 1.0 and 198.0 +- 1.0 microM for the wild type (C-SA) and the mutant (E35D G S), respectively. 2019 Journal of enzyme inhibition and medicinal chemistry Result HIV E35D 125 130 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Additionally, 53% (273/519) of participants in the BIC/FTC/TAF group had at least one pre-existing INSTI-R substitution, the majority of which were polymorphic secondary (accessory) INSTI-R substitutions, with S119P/R/T (32%, 164/519), M50I (22%, 114/519) and E157K/Q (4.4%, 23/519) most frequently observed. 2019 The Journal of antimicrobial chemotherapy Result HIV E157K;E157Q;M50I;S119P;S119R;S119T 260;260;236;210;210;210 267;267;240;219;219;219 INSTI;INSTI 99;182 104;187 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. All participants with pre-existing K65R/N or three or more TAMs had virological suppression at week 48, and none qualified for inclusion in the RAP. 2019 The Journal of antimicrobial chemotherapy Result HIV K65N;K65R 35;35 41;41 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. As previously mentioned, pre-existing M184V or M184I substitutions, associated with resistance to emtricitabine and lamivudine, were found in 10% (54/543) of participants (46 had a V substitution only, 5 had an I substitution only, and 3 had a mixture of V and I). 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 47;38 52;43 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Few participants had three or more TAMs detected (2.4%, 13/543), and only 8 of these participants (1.5%, 8/543) had three or more TAMs that included M41L or L210W, which is the pattern of TAMs associated with clinically significant tenofovir resistance. 2019 The Journal of antimicrobial chemotherapy Result HIV L210W;M41L 157;149 162;153 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Furthermore, pre-existing M184V/I was associated with longer duration of ART treatment: the mean time between ART initiation and BIC/FTC/TAF switch was 14.9 years (range 2.5-28.8 years) for participants with pre-existing M184V/I versus 7.7 years (range 0.3-31.8 years) for participants with WT M184 (P<0.0001 by Student's t-test). 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184I;M184V;M184V 26;221;26;221 33;228;33;228 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M184V/I was present with other primary NRTI-R or NNRTI-R substitutions in 72% (39/54) of participants; other primary NRTI-R substitutions (mainly TAMs) were detected in 41% (22/54), while primary NNRTI-R substitutions were observed in 52% (28/54). 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 0;0 7;7 NNRTI;NNRTI;NRTI;NRTI 49;196;39;117 54;201;43;121 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Most participants with baseline M184V/I were suppressed at week 48 or their last study visit (96%, 52/54). 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 32;32 39;39 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. NNRTI-R substitutions were observed in 23% (124/543) of participants; the most frequently detected substitutions were K103N/S in 12% (64/543) and rilpivirine-associated resistance substitutions (L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C or M320I/L) in 10% (53/543) (Table 3). 2019 The Journal of antimicrobial chemotherapy Result HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;K103N;K103S;L100I;M320I;M320L;V179L;Y181C;Y181I;Y181V;Y188L 211;211;211;211;211;258;251;202;202;118;118;195;267;267;226;233;233;233;244 224;224;224;224;224;263;256;209;209;125;125;200;274;274;231;242;242;242;249 NNRTI 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. No participant had exclusionary substitutions such as K65R or M184V/I by historical genotypic data. 2019 The Journal of antimicrobial chemotherapy Result HIV K65R;M184I;M184V 54;62;62 58;69;69 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. One participant in the boosted PI group, who was on a regimen of ritonavir-boosted darunavir plus abacavir/lamivudine, developed virological failure with a treatment-emergent L74V resistance substitution in RT at week 4. 2019 The Journal of antimicrobial chemotherapy Result HIV L74V 175 179 PI;RT 31;207 33;209 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Participants with documented resistance to emtricitabine or tenofovir or any evidence of prior confirmed virological failure were not eligible to switch to BIC/FTC/TAF; therefore, no participants in the BIC/FTC/TAF group had K65R, M184V/I, or three or more TAMs by historical genotype analysis (Table S1, available as Supplementary data at JAC Online). 2019 The Journal of antimicrobial chemotherapy Result HIV K65R;M184I;M184V 225;231;231 229;238;238 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. PI-R substitutions were observed in 10% (55/543), with M46I/L (4.1%, 22/543) and L90M (2.4%, 13/543) most frequently detected. 2019 The Journal of antimicrobial chemotherapy Result HIV L90M;M46I;M46L 81;55;55 85;61;61 PI 0 2 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Pre-existing K65R/N substitutions were found in 1.3% (7/543) of participants in the BIC/FTC/TAF treatment group. 2019 The Journal of antimicrobial chemotherapy Result HIV K65N;K65R 13;13 19;19 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Pre-existing M184V/I was more frequently observed in participants switching from boosted PI-based regimens than from DTG/ABC/3TC (44 versus 10, respectively, P<0.0001). 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 13;13 20;20 PI 89 91 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Pre-existing NRTI-R substitutions were observed in 16% (89/543) of BIC/FTC/TAF-treated participants; the most frequently detected substitutions were M184V/I in 10% (54/543) and thymidine analogue mutations (TAMs; M41L, D67N, K70R, L210W, T215Y/F and K219Q/N/E/R) in 8.8% (48/543). 2019 The Journal of antimicrobial chemotherapy Result HIV D67N;K219E;K219N;K219Q;K219R;K70R;L210W;M184I;M184V;M41L;T215F;T215Y 219;250;250;250;250;225;231;149;149;213;238;238 223;261;261;261;261;229;236;156;156;217;245;245 NRTI 13 17 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Primary INSTI-R substitutions were infrequent (2.5%, 13/519) and consisted of T97A (1.7%, 9/519) and E92G, Q148H, S147G or Y143H (0.2%, 1/519 each). 2019 The Journal of antimicrobial chemotherapy Result HIV E92G;Q148H;S147G;T97A;Y143H 101;107;114;78;123 105;112;119;82;128 INSTI 8 13 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Similarly, the presence of additional NRTI-R or NNRTI-R substitutions with M184V/I did not affect virological suppression rates at week 48: 97% (38/39) with M184V/I plus other NRTI-R or NNRTI-R versus 93% (14/15) with M184V/I as the only RT substitution (P=0.5). 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184I;M184I;M184V;M184V;M184V 218;75;157;75;157;218 225;82;164;82;164;225 NNRTI;NNRTI;NRTI;NRTI;RT 48;186;38;176;238 53;191;42;180;240 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. The majority of those with pre-existing M184V/I did not have historical genotypic data available (83%, 45/54); however, 17% (9/54) had historical genotypes that did not report M184V at the time of sampling. 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V;M184V 40;40;176 47;47;181 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. The second was included in the RAP (Participant 2 in Table 4) with 76% adherence by pill count and undetectable bictegravir plasma concentrations at the time of resistance testing at week 12, indicating that they had not taken bictegravir for at least 8 days consecutively prior to resistance testing (data on file), and had M184V detected in plasma HIV-1 RNA but no de novo resistance development. 2019 The Journal of antimicrobial chemotherapy Result HIV M184V 325 330 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Two participants with pre-existing M184V/I discontinued early after poor BIC/FTC/TAF adherence and subsequent virological failure. 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 35;35 42;42 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Virological suppression rates at week 48 were similar among participants with and without M184V/I and not significantly different from that of the overall BIC/FTC/TAF-treated population: 96% (52/54) with M184V/I and 99% (482/489) with WT M184 versus 98% (561/570) for all BIC/FTC/TAF-treated participants (P > 0.05 for all comparisons). 2019 The Journal of antimicrobial chemotherapy Result HIV M184I;M184I;M184V;M184V 90;204;90;204 97;211;97;211 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Among these detected mutations, K103 N and V179D + K103R were observed more frequently after 2012. 2019 BMC infectious diseases Result HIV K103N;K103R;V179D 32;51;43 38;56;48 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. For NNRTIs, the most prevalent drug resistance mutations were K103 N (1.59%), V179D + K103R (1.33%), Y181C (0.80%), V108I (0.53%), Y188L (0.53%), G190A (0.53%), H221Y (0.53%), Y318F (0.53%), A98G (0.27%), V106A (0.27%), E138A (0.27%), E138R (0.27%), Y188C (0.27%) and M230 L (0.27%). 2019 BMC infectious diseases Result HIV A98G;E138A;E138R;G190A;H221Y;K103N;K103R;M230L;V106A;V108I;V179D;Y181C;Y188C;Y188L;Y318F 191;220;235;146;161;62;86;268;205;116;78;101;250;131;176 195;225;240;151;166;68;91;274;210;121;83;106;255;136;181 NNRTI 4 10 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. The NRTI mutations included K65R (0.27%), D67N (0.27%), L74 V (0.27%), M184 V (1.06%), L210 W (0.2%) and T215S (0.53%). 2019 BMC infectious diseases Result HIV D67N;K65R;L210W;L74V;M184V;T215S 42;28;87;56;71;105 46;32;93;61;77;110 NRTI 4 8 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Two-thirds of the HIV-infected patients who harbored K103 N variants were detected after 2012, and four-fifths of the patients with V179D + K103R variants were detected after 2012. 2019 BMC infectious diseases Result HIV K103N;K103R;V179D 53;140;132 59;145;137 HIV infections 18 30 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. The most frequent mutations were K103N (12.1%); G190A (5.7%); Y181C (4.3%), which are associated with the high values of resistance to NNRTI described in the study (Table 2). 2019 PloS one Result HIV G190A;K103N;Y181C 48;33;62 53;38;67 NNRTI 135 140 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. 10H and I), suggesting that the G116R mutation augmented the infectivity of both the RGDA/Q112D+A92E and the RGDA/Q112D+G94D viruses. 2019 Journal of virology Result HIV A92E;G116R;G94D;Q112D;Q112D 96;32;120;90;114 100;37;124;95;119 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. 10J and K), demonstrating that the phenotype of the RGDA/Q112D+G94D/G116R virus was shared with that of the RGDA/Q112D+A92E/G116R virus. 2019 Journal of virology Result HIV A92E;G116R;G116R;G94D;Q112D;Q112D 119;68;124;63;57;113 123;73;129;67;62;118 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. 2), we identified the RGDA/Q112D+G94D virus and RGDA/Q112D+G94D/G116R virus after adaptation of the RGDA/Q112D virus in IFN-beta-treated cells but failed to find the RGDA/Q112D virus with the G116R mutation alone. 2019 Journal of virology Result HIV G116R;G94D;Q112D;G116R;G94D;Q112D;Q112D;Q112D 64;59;53;192;33;27;105;171 69;63;58;197;37;32;110;176 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. 3I), suggesting that either the Q4R mutation or the G94D/G116R mutation is sufficient to confer IFN-beta resistance to the RGDA/Q112D background during spreading infection. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q4R 57;52;128;32 62;56;133;35 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. 7C, lane 4, marked with asterisks), whereas the RGDA/Q112D+G94D/G116R virus exhibited normal Gag processing. 2019 Journal of virology Result HIV G116R;G94D;Q112D 64;59;53 69;63;58 Gag 93 96 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. 7D to F), indicating that these mutations did not restore the CypA binding of the RGDA/Q112D virus. 2019 Journal of virology Result HIV Q112D 87 92 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. A complementary assay using cynomolgus monkey (CM) TRIMCyp supported these observations, as the RGDA/Q112D viruses harboring the Q4R or G94D/G116R mutations were completely resistant to the antiviral activity of the CM TRIMCyp protein. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q4R 141;136;101;129 146;140;106;132 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. A previous study showed that a CPSF6 binding-deficient CA mutant (the N74D mutant) exhibits a higher degree of IFN-beta sensitivity than the WT virus. 2019 Journal of virology Result HIV N74D 70 74 Capsid 55 57 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Adaptation of the RGDA/Q112D virus in IFN-beta-treated T cells. 2019 Journal of virology Result HIV Q112D 23 28 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Although the difference was rather small (20.1% versus 8.1% for the RGDA/Q112D virus and the WT virus, respectively), the difference was statistically significant (P < 0.01). 2019 Journal of virology Result HIV Q112D 73 78 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. CA mutations in the adapted virus confer IFN-beta resistance to the RGDA/Q112D virus. 2019 Journal of virology Result HIV Q112D 73 78 Capsid 0 2 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Consistent with previous studies, infections of the NL4-3 G94D and A92E viruses were enhanced by CypA knockout or CsA treatment in HeLa cells. 2019 Journal of virology Result HIV A92E 67 71 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Consistent with the previous observation in THP-1 cells, the A105T virus showed higher IFN-beta sensitivity than the WT virus in Jurkat cells. 2019 Journal of virology Result HIV A105T 61 66 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Figures 5B and C show that the levels of the second-strand transfer products of the RGDA/Q112D virus were more strongly suppressed by IFN-beta than those of the WT virus and that the Q4R and G94D/G116R substitutions abolished the suppressive effects of the RGDA/Q112D substitutions in the presence of IFN-beta. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D;Q4R 196;191;89;262;183 201;195;94;267;186 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Finally, we examined the IFN-beta sensitivity of the RGDA/Q112D+A92E/G116R virus and found that the virus was completely resistant even in the highest concentration (200 U per ml) of IFN-beta. 2019 Journal of virology Result HIV A92E;G116R;Q112D 64;69;58 68;74;63 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Furthermore, the RGDA/Q112D+Q4R and RGDA/Q112D+G94D/G116R viruses showed partial but significant IFN-beta resistance in the monocytic cell line THP-1. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D;Q4R 52;47;41;22;28 57;51;46;27;31 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Here we observed that the G116R mutation did not affect the CypA sensitivity of the NL4-3 A92E and G94D viruses. 2019 Journal of virology Result HIV G116R;G94D 26;99 31;103 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. However, the relative infectivity of the RGDA/Q112D virus in CPSF6-358-expressing cells was not as low as that of the WT virus. 2019 Journal of virology Result HIV Q112D 46 51 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. IFN-beta-treated Jurkat and MT4 cells were infected with the RGDA/Q112D virus, and viral replication was monitored during an extended period of culture. 2019 Journal of virology Result HIV Q112D 66 71 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Importantly, the relative infectivity of the RGDA/Q112D+Q4R virus in CPSF6-358-expressing cells was lower than that of the RGDA/Q112D virus (6.5% versus 20.1%, P < 0.0001). 2019 Journal of virology Result HIV Q112D;Q112D;Q4R 50;128;56 55;133;59 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In agreement with previous reports, the N74D and P90A viruses were more resistant to MxB than the WT virus. 2019 Journal of virology Result HIV N74D;P90A 40;49 44;53 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, infection of the N74D virus was not affected by CPSF6-358. 2019 Journal of virology Result HIV N74D 30 34 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the G94D/G116R mutations decreased the CPSF6-358 sensitivity of the RGDA/Q112D virus (20.1% versus 46.6% for the relative infectivity of the RGDA/Q112D virus and the RGDA/Q112D+G94D/G116R virus in CPSF6-358-expressing cells, respectively; P < 0.01). 2019 Journal of virology Result HIV G116R;G94D;Q112D;G116R;G94D;Q112D;Q112D 195;190;184;22;17;86;159 200;194;189;27;21;91;164 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the relative infectivity of the RGDA/Q112D+G94D/G116R virus was 2-fold higher than that of the WT virus. 2019 Journal of virology Result HIV G116R;G94D;Q112D 61;56;50 66;60;55 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the RGDA/Q112D and RGDA/Q112D+G94D/G116R viruses delayed the loss of sensitivity to nevirapine compared with the WT virus only in IFN-beta-treated cells. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D 48;43;37;22 53;47;42;27 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the RGDA/Q112D viral particles contained marginal amount of CypA. 2019 Journal of virology Result HIV Q112D 22 27 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the RGDA/Q112D virus and the RGDA/Q112D+G94D/G116R virus developed a slower loss of sensitivity to nevirapine than the WT virus, but only in IFN-beta-treated cells. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D 58;53;47;22 63;57;52;27 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In the context of VSV-G-pseudotyped viruses that had undergone a single round of infection, the G94D/G116R mutation and the G94D mutation conferred IFN-beta resistance to the WT virus, while the Q4R mutation did not affect IFN-beta sensitivity in this WT CA context. 2019 Journal of virology Result HIV G116R;G94D;G94D;Q4R 101;96;124;195 106;100;128;198 Capsid 255 257 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Interestingly, the RGDA/Q112D+G94D/G116R+A105T virus exhibited enhanced IFN-beta sensitivity compared with the RGDA/Q112D+G94D/G116R virus. 2019 Journal of virology Result HIV A105T;G116R;G116R;G94D;G94D;Q112D;Q112D 41;35;127;30;122;24;116 46;40;132;34;126;29;121 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Interestingly, this acceleration of the initiation of uncoating and the faster initiation and completion of reverse transcription are intrinsic to the RGDA/Q112D+Q4R virus, as the addition of IFN-beta had no effect on the kinetics of capsid integrity loss or reverse transcription. 2019 Journal of virology Result HIV Q112D;Q4R 156;162 161;165 RT;RT;Capsid 108;259;234 129;280;240 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It should be noted that the G116R mutation was found only in the clones that also harbored the G94D mutation. 2019 Journal of virology Result HIV G116R;G94D 28;95 33;99 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It should be noted that the replication-defective RGDA/Q112D+G94D virus showed abnormal Gag processing in immunoblots of virions. 2019 Journal of virology Result HIV G94D;Q112D 61;55 65;60 Gag 88 91 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Limited contributions of CPSF6 and CypA for IFN-beta resistance of the RGDA/Q112D virus harboring the Q4R or G94D/G116R mutations. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q4R 114;109;76;102 119;113;81;105 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Moreover, only the G116R mutation was associated with the G94D mutation. 2019 Journal of virology Result HIV G116R;G94D 19;58 24;62 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Next, we examined the relationship between the A92E CA mutation and the G116R mutation since the NL4-3 A92E CA mutant shares several phenotypes with the NL4-3 G94D CA mutant in terms of sensitivity to CypA and an inability to infect nondividing cells. 2019 Journal of virology Result HIV A92E;G116R 47;72 51;77 Capsid;Capsid;Capsid 52;108;164 54;110;166 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Notably, RGDA/Q112D viruses harboring Q4R or G94D/G116R mutations efficiently replicated in both untreated and IFN-beta-treated cells. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q4R 50;45;14;38 55;49;19;41 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Notably, the RGDA/Q112D+G94D/G116R virus was completely IFN-beta resistant even to the highest concentration (200 U per ml) of IFN-beta. 2019 Journal of virology Result HIV G116R;G94D;Q112D 29;24;18 34;28;23 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Previous studies demonstrated that the impaired infectivity of CsA-dependent CA mutants, including those with the A92E and G94D mutations, in certain cell types was rescued by additional CA mutations, such as P90A and A105T. 2019 Journal of virology Result HIV A105T;A92E;G94D;P90A 218;114;123;209 223;118;127;213 Capsid;Capsid 77;187 79;189 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Sequence analysis of 20 clones of TOPO plasmids revealed the presence of three types of CA sequences in these clones: the RGDA/Q112D+Q4R, RGDA/Q112D+G94D, and RGDA/Q112D+G94D/G116R clones. 2019 Journal of virology Result HIV G116R;G94D;Q112D;G94D;Q112D;Q112D;Q4R 175;170;164;149;127;143;133 180;174;169;153;132;148;136 Capsid 88 90 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. show that RGDA/Q112D+Q4R progresses to initialize reverse transcription earlier and to a faster completion of the process. 2019 Journal of virology Result HIV Q112D;Q4R 15;21 20;24 RT 50 71 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Specifically, the RGDA/Q112D+Q4R virus showed a more rapid loss of sensitivity to nevirapine than the RGDA/Q112D virus and the WT virus in both untreated and IFN-beta-treated cells. 2019 Journal of virology Result HIV Q112D;Q112D;Q4R 23;107;29 28;112;32 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Strikingly, we observed that RGDA/Q112D+Q4R (Movie S3) had faster kinetics for the initiation of uncoating, a process that has been shown to take place after the first-strand transfer. 2019 Journal of virology Result HIV Q112D;Q4R 34;40 39;43 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The frequency of the RGDA/Q112D+Q4R, RGDA/Q112D+G94D, and RGDA/Q112D+G94D/G116R sequences was 30%, 5%, and 10%, respectively. 2019 Journal of virology Result HIV G116R;G94D;Q112D;G94D;Q112D;Q112D;Q4R 74;69;63;48;26;42;32 79;73;68;52;31;47;35 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The G94D/G116R mutations did not significantly affect the sensitivity of the RGDA/Q112D virus to MxB, as we observed no difference in sensitivity to MxB between the RGDA/Q112D virus and the RGDA/Q112D+G94D/G116R virus (38.5% versus 40.2%). 2019 Journal of virology Result HIV G116R;G94D;Q112D;G116R;G94D;Q112D;Q112D 206;201;195;9;4;82;170 211;205;200;14;8;87;175 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The IFN-beta sensitivity of the RGDA/Q112D+G94D virus was not tested because it was not infectious. 2019 Journal of virology Result HIV G94D;Q112D 43;37 47;42 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The individual impacts of these CA mutations on IFN-beta resistance of the RGDA/Q112D virus were not specific to Jurkat cells since we observed a similar phenotype in another CD4-positive T cell line, MT4 cells. 2019 Journal of virology Result HIV Q112D 80 85 Capsid 32 34 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation accelerates initiation of uncoating of the RGDA/Q112D virus. 2019 Journal of virology Result HIV Q112D;Q4R 65;4 70;7 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation accelerates the kinetics of completion of reverse transcription of the RGDA/Q112D virus. 2019 Journal of virology Result HIV Q112D;Q4R 93;4 98;7 RT 59 80 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation enhanced the sensitivity of the RGDA/Q112D virus to MxB restriction, despite the fact that the Q4R mutation conferred IFN-beta resistance to the RGDA/Q112D virus. 2019 Journal of virology Result HIV Q112D;Q112D;Q4R;Q4R 54;167;4;112 59;172;7;115 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation sensitizes the RGDA/Q112D virus to MxB-mediated restriction despite conferring IFN-beta resistance. 2019 Journal of virology Result HIV Q112D;Q4R 37;4 42;7 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The R116 residue could form a salt bridge with the D94 residue, suggesting that the G116R mutation rescued the RGDA/Q112D+G94D virus by restoring the interaction between CA amino acids 94 and 116. 2019 Journal of virology Result HIV G116R;G94D;Q112D 84;122;116 89;126;121 Capsid 170 172 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The relative infectivity of the RGDA/Q112D+Q4R virus in CPSF6-358-expressing cells was comparable to that of the WT virus (6.5% versus 8.1%). 2019 Journal of virology Result HIV Q112D;Q4R 37;43 42;46 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D virus obtained IFN-beta resistance with the G94D mutation followed by the G116R mutation to compensate for the impaired infectivity. 2019 Journal of virology Result HIV G116R;G94D;Q112D 89;59;9 94;63;14 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D virus was even more resistant to MxB than the N74D virus (38.5% versus 28.9%). 2019 Journal of virology Result HIV N74D;Q112D 61;9 65;14 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D+A92E/G116R virus exhibited infectivity significantly higher than that of the RGDA/Q112D+A92E virus. 2019 Journal of virology Result HIV A92E;G116R;Q112D;A92E;Q112D 15;20;9;103;97 19;25;14;107;102 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D+G94D virus was severely defective, with 0.4% infectivity relative to that of the WT virus. 2019 Journal of virology Result HIV G94D;Q112D 15;9 19;14 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D+Q4R virus was more resistant to IFN-beta than the RGDA/Q112D or the WT virus at all IFN-beta concentrations. 2019 Journal of virology Result HIV Q112D;Q112D;Q4R 9;70;15 14;75;18 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These observations suggest a limited role of MxB in the IFN-beta sensitivity of the RGDA/Q112D virus. 2019 Journal of virology Result HIV Q112D 89 94 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These observations suggest that intact binding with both CPSF6 and CypA may not be necessary for evasion of the RGDA/Q112D virus from IFN-beta-mediated inhibition. 2019 Journal of virology Result HIV Q112D 117 122 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These observations suggest that the G116R mutation rescued the RGDA/Q112D+G94D virus by compensating for the abnormal Gag processing of the RGDA/Q112D+G94D virus. 2019 Journal of virology Result HIV G116R;G94D;G94D;Q112D;Q112D 36;74;151;68;145 41;78;155;73;150 Gag 118 121 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These results demonstrate that the Q4R and G94D/G116R mutations in CA in adapted viruses are sufficient to provide IFN-beta resistance to RGDA/Q112D viruses. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q4R 48;43;143;35 53;47;148;38 Capsid 67 69 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These results indicate that a step or steps occurring until the completion of second-strand transfer of reverse transcription by the RGDA/Q112D virus were at least one of the targets for IFN-beta. 2019 Journal of virology Result HIV Q112D 138 143 RT 104 125 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These results reveal that the Q4R mutation specifically conferred IFN-beta resistance in the context of the RGDA/Q112D virus, whereas the G94D/G116R mutations conferred IFN-beta resistance to both the RGDA/Q112D virus and the WT virus. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D;Q4R 143;138;113;206;30 148;142;118;211;33 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These results suggest that the G94D mutation is responsible for conferring IFN-beta resistance to the RGDA/Q112D virus, while the G116R mutation is a compensatory mutation to restore the impaired infectivity of the RGDA/Q112D+G94D virus. 2019 Journal of virology Result HIV G116R;G94D;G94D;Q112D;Q112D 130;31;226;107;220 135;35;230;112;225 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These results suggest that the Q4R mutation specifically enhanced the CPSF6-358 sensitivity of the RGDA/Q112D virus. 2019 Journal of virology Result HIV Q112D;Q4R 104;31 109;34 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. This is consistent with the hypothesis that the RGDA/Q112D virus is more sensitive to IFN-beta than the WT virus, and we found a significantly decreased infectivity of the RGDA/Q112D virus in IFN-beta-treated cells compared with that of the WT virus. 2019 Journal of virology Result HIV Q112D;Q112D 53;177 58;182 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. This result suggested that the prominent resistance of the RGDA/Q112D+G94D/G116R virus to IFN-beta-mediated restriction was on a delicate balance; thus, just one CA mutation would reverse this phenotype. 2019 Journal of virology Result HIV G116R;G94D;Q112D 75;70;64 80;74;69 Capsid 162 164 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. To determine if the RGDA/Q112D virus could develop IFN-beta resistance, we adapted the virus through long-term culture in IFN-beta-treated Jurkat and MT4 cells. 2019 Journal of virology Result HIV Q112D 25 30 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. To further characterize the Q4R and G94D/G116R mutations, we examined their impact on IFN-beta resistance in the context of WT CA. 2019 Journal of virology Result HIV G116R;G94D;Q4R 41;36;28 46;40;31 Capsid 127 129 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. To test the IFN-beta sensitivity of the RGDA/Q112D virus, Jurkat cells treated with IFN-beta or left untreated were challenged with green fluorescent protein (GFP)-expressing viruses. 2019 Journal of virology Result HIV Q112D 45 50 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. To this end, we introduced the A105T mutation into the WT and RGDA/Q112D+G94D/G116R viruses. 2019 Journal of virology Result HIV G116R;G94D;Q112D;A105T 78;73;67;31 83;77;72;36 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Upon analysis of the kinetics of the initiation of uncoating of hundreds of viral particles, we observed that HIV-iGFP harboring RGDA/Q112D (see Movie S1 in the supplemental material) and RGDA/Q112D+G94D/G116R CA sequences showed the same kinetics of initiation of uncoating as HIV-iGFP harboring WT CA. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D 204;199;193;134 209;203;198;139 Capsid;Capsid 210;300 212;302 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We also observed that the G94D mutation conferred IFN-beta resistance to the WT virus. 2019 Journal of virology Result HIV G94D 26 30 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We assume that the RGDA/Q112D virus first mutated the G94D position and then acquired the G116R mutation. 2019 Journal of virology Result HIV G116R;G94D;Q112D 90;54;24 95;58;29 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We became interested in how such mutations affected the IFN-beta resistance of the RGDA/Q112D+G94D/G116R virus. 2019 Journal of virology Result HIV G116R;G94D;Q112D 99;94;88 104;98;93 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We began to investigate the impact of the Q4R and G94D/G116R mutations on these events in the RGDA/Q112D context. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q4R 55;50;99;42 60;54;104;45 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We concluded that the G94D mutation was responsible for conferring IFN-beta resistance to the RGDA/Q112D virus, whose impaired infectivity was rescued by the G116R mutation. 2019 Journal of virology Result HIV G116R;G94D;Q112D 158;22;99 163;26;104 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We concluded that the RGDA/Q112D+Q4R mutation accelerated both reverse transcription completion kinetics and the initiation of uncoating relative to those for the RGDA/Q112D and the WT viruses in the presence and absence of IFN-beta. 2019 Journal of virology Result HIV Q112D;Q112D;Q4R 27;168;33 32;173;36 RT 63 84 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We examined whether the G116R mutation augments the infectivity of the RGDA/Q112D+A92E virus. 2019 Journal of virology Result HIV A92E;G116R;Q112D 82;24;76 86;29;81 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We first examined the IFN-beta sensitivity of the RGDA/Q112D virus, since the P90A mutation in CA, which results in a CypA binding-deficient mutant, has been shown to increase the sensitivity to IFN-alpha-mediated inhibition. 2019 Journal of virology Result HIV P90A;Q112D 78;55 82;60 Capsid 95 97 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We found that, like its WT counterpart, the RGDA/Q112D virus was blocked by CPSF6-358. 2019 Journal of virology Result HIV Q112D 49 54 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We further tested the IFN-beta sensitivity of NL4-3 CA mutants harboring the Q4R and G94D/G116R mutations in a multiround replication assay by using untreated Jurkat cells or cells treated with 100 U per ml of IFN-beta. 2019 Journal of virology Result HIV G116R;G94D;Q4R 90;85;77 95;89;80 Capsid 52 54 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We observed a similar phenotype with the additional mutations in RGDA/Q112D+Q4R and RGDA/Q112D+G94D/G116R viral particles. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D;Q4R 100;95;89;70;76 105;99;94;75;79 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We observed a statistically significant difference between the WT and A105T viruses in cells treated with 2 U/ml of IFN-beta. 2019 Journal of virology Result HIV A105T 70 75 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We observed that other clones (55%) encoded the RGDA/Q112D mutations, meaning that any substitution or reversion to the WT sequence in viruses with the original five mutations (H87R, A88G, P90D, P93A, and Q112D) was not detected. 2019 Journal of virology Result HIV A88G;H87R;P90D;P93A;Q112D;Q112D 183;177;189;195;53;205 187;181;193;199;58;210 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We observed that the RGDA/Q112D+Q4R virus had a 1.5-fold higher infectivity than the WT virus. 2019 Journal of virology Result HIV Q112D;Q4R 26;32 31;35 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We observed that while the relative infectivity of the RGDA/Q112D and RGDA/Q112D+G94D/G116R viruses was decreased by IFN-beta, that of the WT and the RGDA/Q112D+Q4R viruses was not affected. 2019 Journal of virology Result HIV G116R;G94D;Q112D;Q112D;Q112D;Q4R 86;81;75;60;155;161 91;85;80;65;160;164 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We observed the robust replication of the RGDA/Q112D virus in untreated cells. 2019 Journal of virology Result HIV Q112D 47 52 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. While the RGDA/Q112D virus was unable to escape IFN-beta inhibition in MT4 cells (data not shown), the RGDA/Q112D virus started to replicate in IFN-beta-treated Jurkat cells approximately 5 weeks after infection. 2019 Journal of virology Result HIV Q112D;Q112D 15;108 20;113 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. A change in conformation was observed in loop V5 to accommodate the bulky tyrosine side chain from the G458Y substitution (S5 and S6 Fig). 2019 PLoS pathogens Result HIV G458Y 103 108 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Additionally, E64K and A316W were introduced to stabilize the Env in the closed conformation. 2019 PLoS pathogens Result HIV A316W;E64K 23;14 28;18 Env 62 65 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Among the substitutions at position 279 that were testable as Man5-enriched viruses, none proved superior to N279K (S2 Table). 2019 PLoS pathogens Result HIV N279K 109 114 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Another mutation, G458Y (V5 proximal), was found to make CH505TF/GnT1 moderately sensitive to neutralization by CH235 UCA2. 2019 PLoS pathogens Result HIV G458Y 18 23 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. As shown in Fig 4 and discussed below, immunogens bearing various combinations of N279K, G458Y and/or Man5-enrichment offer potential prime-boost strategies to determine the most effective maturation pathway from early precursor to mature bnAb. 2019 PLoS pathogens Result HIV G458Y;N279K 89;82 94;87 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. As single mutants, Man5-enriched N279K and G458Y were 92-fold and 973-fold less susceptible, respectively, than the Man5-enriched double mutant, illustrating potent synergy between the two mutations. 2019 PLoS pathogens Result HIV G458Y;N279K 43;33 48;38 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Based on our results, CH505TF.N279K.G458Y/GnT1- is predicted to be highly sensitive for detecting vaccine-elicited early precursors of the CH235/CH235.12 lineage, where samples testing positive may be assayed against the N280D knock-out to confirm CD4bs-specificity (Fig 1, S1H and S1I Fig). 2019 PLoS pathogens Result HIV N280D 221 226 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. CH235 UCA2 bound with high affinity (9 nM) to Man5-enriched CH505.N279K.G458Y, and bound with incrementally lower affinities to the other antigens, as predicted by neutralization potency against corresponding Env-pseudotyped viruses (Fig 2C, S3 Fig). 2019 PLoS pathogens Result HIV G458Y;N279K 72;66 77;71 Env 209 212 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Confirmation of CD4bs specificity is not possible with N280D and other known CD4bs bnAb resistance mutations because these mutations did not impart resistance to CH103 and its intermediates. 2019 PLoS pathogens Result HIV N280D 55 60 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Cryo-EM structure of CH235 UCA2 bound to stabilized CH505TF.N279K.G458Y.SOSIP.664 Env. 2019 PLoS pathogens Result HIV G458Y;N279K 66;60 71;65 Env 82 85 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Despite the modest resolution of the cryo-EM reconstruction, density was well-resolved for the antibody-gp120 interface (S5 Fig), allowing unambiguous placement of the complementarity determining regions (CDRs) of the antibody, as well as its epitope on the Man5-enriched CH505TF.N279K.G458Y.SOSIP.664 Env trimer. 2019 PLoS pathogens Result HIV G458Y;N279K 286;280 291;285 gp120;Env 104;302 109;305 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. In addition to the N279K and G458Y mutations, Man5-enrichment of the CH505TF.N279K.G458Y.SOSIP.664 trimer enhanced binding to CH235 UCA2. 2019 PLoS pathogens Result HIV G458Y;G458Y;N279K;N279K 29;83;19;77 34;88;24;82 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. In an attempt to overcome the barrier to CH235 UCA2 neutralization, we combined Man5-enrichment with an N279K change in gp120 loop D that triggered the CH235 lineage in donor CH505. 2019 PLoS pathogens Result HIV N279K 104 109 gp120 120 125 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. In summary, the cryo-EM structure provides atomic level insights into how the G458Y and N279K mutations permit high affinity binding between the engineered Man5-enriched CH505TF.N279K.G458Y.SOSIP.664 and CH235 UCA2. 2019 PLoS pathogens Result HIV G458Y;G458Y;N279K;N279K 78;184;88;178 83;189;93;183 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Indeed, the germline-targeting CH505TF.N279K.G458Y.SOSIP.664/GnT1- immunogen induced CH235 early precursors in CH235 UCA2 knock-in mice, overcoming an improbable K19T heavy chain mutation, and induced a neutralization signature consistent with CH235 early precursors in rhesus macaques (Saunders et al., submitted). 2019 PLoS pathogens Result HIV K19T 162 166 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Man5-enriched N279K, G458Y and N279K.G458Y mutants were approximately 100-10,000-fold more sensitive to I4, and were 1.7-9.6-fold more sensitive to later intermediates of CH235 compared to Man5-enriched CH505TF (Fig 1, S1I-S1K Fig). 2019 PLoS pathogens Result HIV G458Y;G458Y;N279K;N279K 21;37;14;31 26;42;19;36 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. N279K and G458Y mutations. 2019 PLoS pathogens Result HIV G458Y;N279K 10;0 15;5 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Nonetheless, combining either G458C or G458L with N279K provided only 2-3-fold improved susceptibility to CH235 UCA2 and no improved susceptibility to the CH235 intermediates compared to N279K.G458Y (S2 Table). 2019 PLoS pathogens Result HIV G458C;G458L;G458Y;N279K;N279K 30;39;193;50;187 35;44;198;55;192 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. On the other hand, two substitutions at position 458 (G458C and G458L) provided modest improvement over G458Y as single mutants (S2 Table). 2019 PLoS pathogens Result HIV G458C;G458L;G458Y 54;64;104 60;69;109 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The CH235 UCA2 also made extensive contacts with loop D and loop V5, which are the sites of the N279K and the G458Y mutations, respectively (Fig 3B and 3C, S5 and S6 Figs). 2019 PLoS pathogens Result HIV G458Y;N279K 110;96 115;101 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The combination of the neutralization data and structural data provide strong support for a stable and functionally relevant interaction between the inferred germline antibody CH235 UCA2 and the CH505TF.N279K.G458Y Env. 2019 PLoS pathogens Result HIV G458Y;N279K 209;203 214;208 Env 215 218 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The double mutation (N279K.G458Y) in CH505TF was synergistic in overcoming the barrier to CH235 UCA2 neutralization, with additional synergy provided by Man5-enrichment, resulting in a remarkable IC50 of 0.04 mug/ml against the Man5-enriched double mutant (Fig 1, Fig 2B and 2C, S1H Fig). 2019 PLoS pathogens Result HIV G458Y;N279K 27;21 32;26 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The N279K has been previously reported as the natural CH505 M5 variant of the CH505 transmitted/founder virus]. 2019 PLoS pathogens Result HIV N279K 4 9 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The remarkable neutralization of the N279K.G458Y virus by CH235 UCA2 led us to investigate whether further optimization was possible by substituting other amino acids at these two positions. 2019 PLoS pathogens Result HIV G458Y;N279K 43;37 48;42 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. These two mutations, N279K and G458Y, also had an impact on intermediates of CH235. 2019 PLoS pathogens Result HIV G458Y;N279K 31;21 36;26 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Three mutations in V5 (N461A, N462A and T463A) had no effect but a fourth mutation in the CD4-binding loop (S365P) conferred resistance to the UCA and intermediates while not conferring resistance to mature CH103 (S4 Table). 2019 PLoS pathogens Result HIV N461A;N462A;S365P;T463A 23;30;108;40 28;35;113;45 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. To understand the structural basis for CH235 UCA2 recognition of Env with the N279K and G458Y mutations, we determined the structure of CH235 UCA2 in complex with Man5-enriched stabilized CH505TF.N279K.G458Y.SOSIP.664 by cryogenic electron microscopy (cryo-EM) (Fig 3, S4 and S5 Figs, S3 Table). 2019 PLoS pathogens Result HIV G458Y;G458Y;N279K;N279K 88;202;78;196 93;207;83;201 Env 65 68 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. We examined N279K and G458Y in the context of CH505TF rather than the glycan deleted variants because glycan deletion provided little or no benefit and sometimes was detrimental for neutralization by CH235 intermediates I3 and I1 (Fig 1). 2019 PLoS pathogens Result HIV G458Y;N279K 22;12 27;17 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. K103N (5.8%) comprised of the majority of NNRTI TDRMs. 2019 Heliyon Result HIV K103N 0 5 NNRTI 42 47 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. The only mutation associated with INSTI resistance was E138A (2.9%). 2019 Heliyon Result HIV E138A 55 60 INSTI 34 39 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. The presence of E138A, a mutation associated with INSTI resistance, was noted from 2007-2013, however no significant trend was observed (p = 0.74). 2019 Heliyon Result HIV E138A 16 21 INSTI 50 55 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. The prevalence of individual NRTI TDRMs was low at <3%, the two most frequent being K70R (2.4%) and M41L (1.9%). 2019 Heliyon Result HIV K70R;M41L 84;100 88;104 NRTI 29 33 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. The prevalence of individual PI TDRMs was generally <0.5% except for L90M (1.0%). 2019 Heliyon Result HIV L90M 69 73 PI 29 31 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. A more recent analysis acknowledges the protein-DNA interaction role of T124 and states that the interaction is lost with mutation T124A. 2019 Frontiers in microbiology Result HIV T124A 131 136 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Also, in position 66, we only found the T66K variant. 2019 Frontiers in microbiology Result HIV T66K 40 44 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Also, the VG1 position 157, which may have the mutation E157Q, does not appear to influence the INSTI therapy but is selected in treated patients. 2019 Frontiers in microbiology Result HIV E157Q 56 61 INSTI 96 101 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Another example of this possible compensatory mechanism is the co-occurrence of K215N and N222K. 2019 Frontiers in microbiology Result HIV K215N;N222K 80;90 85;95 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. As mentioned above, S119R may have implications in DNA binding. 2019 Frontiers in microbiology Result HIV S119R 20 25 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. By the observed co-occurrence, E138K could also be compensating for K156N. 2019 Frontiers in microbiology Result HIV E138K;K156N 31;68 36;73 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Cluster A also displays the mutations T124N and T124A, found VG4 positions. 2019 Frontiers in microbiology Result HIV T124A;T124N 48;38 53;43 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Cluster D also has S230N, which is not associated with resistance to RAL; however, another mutation in this position (S230R) is associated with resistance to DTG. 2019 Frontiers in microbiology Result HIV S230N;S230R 19;118 24;123 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Cluster D, on the other hand, has E157Q, which is a resistance-related mutation with minimal effects on RAL, and occurs in a VG1 position. 2019 Frontiers in microbiology Result HIV E157Q 34 39 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Cluster F also has mutations T125V and T125A, which are VG4 positions. 2019 Frontiers in microbiology Result HIV T125A;T125V 39;29 44;34 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Curiously, four isolates showed mutations related to more than one of the three main resistance pathways: two from Italy, one with both N155H and Y143R and another with Q148H and Y143H; one from Canada with N155H and Y143C; and one from France with N155H and Q148R. 2019 Frontiers in microbiology Result HIV N155H;N155H;N155H;Q148H;Q148R;Y143C;Y143H;Y143R 136;207;249;169;259;217;179;146 141;212;254;174;264;222;184;151 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. E138K co-occurs with three mutations of lysine residues, one of them in K156 (K156N). 2019 Frontiers in microbiology Result HIV K156N;E138K 78;0 83;5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Furthermore, position 230, which may bear the mutation S230R in patients treated with RAL, EVG, or DTG also displays low entropies in both treated and non-treated patients. 2019 Frontiers in microbiology Result HIV S230R 55 60 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. G118R is considered an accessory mutation and shows a significant reduction in RAL susceptibility. 2019 Frontiers in microbiology Result HIV G118R 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. However, in this case, the mutation N155H is not an accessory mutation and the mechanism by which it causes resistance stays unclear. 2019 Frontiers in microbiology Result HIV N155H 36 41 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. However, it is not clear how the presence of G118R affects the variability in the neighbor S119. 2019 Frontiers in microbiology Result HIV G118R 45 50 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. In 119, the natural polymorphism S119R is described as weakly selected in RAL-treated patients. 2019 Frontiers in microbiology Result HIV S119R 33 38 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. In VG1 two resistance-related positions (114 and 121) had zero entropy in both datasets, probably because the resistance mutation H114Y is rare, and F121Y is rarely selected in vivo by RAL. 2019 Frontiers in microbiology Result HIV F121Y;H114Y 149;130 154;135 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. It also shows that Y143R has its own set of co-occurring mutations. 2019 Frontiers in microbiology Result HIV Y143R 19 24 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. It is also important to note that its neighbor G118 may show the mutation G118R. 2019 Frontiers in microbiology Result HIV G118R 74 79 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. It is also possible to see that except for Y143R and E138K, all the mutations on VG3 positions are in cluster A (Figure 6), which means they either co-occur or share co-occurring partners. 2019 Frontiers in microbiology Result HIV E138K;Y143R 53;43 58;48 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. It is known that arginine residues are commonly found in interfaces between proteins and DNA minor grooves, it could be possible that mutation S119R, as well as G118R, enhances the DNA binding, and therefore acts as a compensatory mechanism for primary resistance mutations. 2019 Frontiers in microbiology Result HIV G118R;S119R 161;143 166;148 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Moreover, within this cluster, mutation S230N co-occurs with K160Q, which takes place in a DNA-anchoring lysine. 2019 Frontiers in microbiology Result HIV K160Q;S230N 61;40 66;45 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Mutations E92Q and T66K - which are also resistance-related mutations - were not present in frequencies high enough to be considered in the network. 2019 Frontiers in microbiology Result HIV E92Q;T66K 10;19 14;23 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Mutations S119RPG are also present in this cluster. 2019 Frontiers in microbiology Result HIV S119G;S119P;S119R 10;10;10 17;17;17 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Other mutations that co-occur with E138K are K215N and K14R. 2019 Frontiers in microbiology Result HIV E138K;K14R;K215N 35;55;45 40;59;50 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Other resistance-related mutations found in cluster A, are D232N and M50I - both involved in increased resistance to DTG. 2019 Frontiers in microbiology Result HIV D232N;M50I 59;69 64;73 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Position 97, which is known for bearing the T97A accessory mutation, is also in this variability group. 2019 Frontiers in microbiology Result HIV T97A 44 48 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Position L74 has two mutations within this cluster: L74M and L74I, both are described as resistance-related, also described as having minimal effects in INSTI therapy, as previously said. 2019 Frontiers in microbiology Result HIV L74I;L74M 61;52 65;56 INSTI 153 158 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Positions 140, 143, 148 and 155 (involved in major resistance pathways, are in VG3, as well as position 138, which may display the resistance mutations E138KAT. 2019 Frontiers in microbiology Result HIV E138A;E138K;E138T 152;152;152 159;159;159 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S119R is known as a resistance-related mutation and enhances primary resistance mechanisms. 2019 Frontiers in microbiology Result HIV S119R 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S119R seems to be selected in RAL treated patients, and alone seems to have only minor effects in INSTIs, and within cluster E, S119R co-occurs with L74M. 2019 Frontiers in microbiology Result HIV L74M;S119R;S119R 149;128;0 153;133;5 INSTI 98 104 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. speculated that the mutation N155H disrupts the coordinates of the Mg2+ ions in the active site. 2019 Frontiers in microbiology Result HIV N155H 29 34 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T66I reduces EVG susceptibility and has minimal effects over RAL, while T66K reduces both RAL and EVG susceptibility. 2019 Frontiers in microbiology Result HIV T66K;T66I 72;0 76;4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The latter co-occurs with G163R, which is an accessory mutation to the N155H pathway selected in patients receiving RAL. 2019 Frontiers in microbiology Result HIV G163R;N155H 26;71 31;76 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The major cluster (A), contains two mutations in the main resistance-related positions (Q148H and N155H), as well as the major resistance mutation G140S. 2019 Frontiers in microbiology Result HIV G140S;N155H;Q148H 147;98;88 152;103;94 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The mutations that co-occur with Q148R, Q148H, N155H, Y143R, E138K, and T97A are shown in Table 3. 2019 Frontiers in microbiology Result HIV E138K;N155H;Q148H;Q148R;T97A;Y143R 61;47;40;33;72;54 66;52;45;38;76;59 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The position T97 - that may bear the accessory mutation T97A - is 15 A away from the closest RAL atom. 2019 Frontiers in microbiology Result HIV T97A 56 60 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The rare P142T mutation was reported as selected in vitro by DTG and in vivo by RAL. 2019 Frontiers in microbiology Result HIV P142T 9 14 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The residue 92, may show the mutation E92Q that was shown to reduce RAL susceptibility. 2019 Frontiers in microbiology Result HIV E92Q 38 42 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The resistance-related mutations found in the network were L74M, L74I, T97A, E138K, G140S, Y143R, Q148H, Q148R, N155H, E157Q, G163R, M50I, and S119R. 2019 Frontiers in microbiology Result HIV E138K;E157Q;G140S;G163R;L74I;L74M;M50I;N155H;Q148H;Q148R;S119R;T97A;Y143R 77;119;84;126;65;59;133;112;98;105;143;71;91 82;124;89;131;69;63;137;117;103;110;148;75;96 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The resistance-related mutations Y143R and E138K are populated in their own clusters, respectively B and C, which are populated mostly by mutations in low-entropy positions, and no other resistance-related mutation. 2019 Frontiers in microbiology Result HIV E138K;Y143R 43;33 48;38 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Therefore, mutation E138K could be compensating for K215N, given their co-occurrence and structural proximity. 2019 Frontiers in microbiology Result HIV E138K;K215N 20;52 25;57 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. This is in agreement with the fact that resistance pathways are mutually exclusive, and the N155H pathway is more likely to be further converted into the Q148HKR variants than into Y143CRH. 2019 Frontiers in microbiology Result HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 92;154;154;154;181;181;181 97;161;161;161;188;188;188 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. This observation highlights the fact that T97A does not play a role impairing RAL binding but somehow compensates for the impacts of mutations Y143RC and N155H and Q148H + G140S. 2019 Frontiers in microbiology Result HIV G140S;N155H;Q148H;T97A;Y143C;Y143R 172;154;164;42;143;143 177;159;169;46;149;149 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. This residue is involved in resistance to DTG when bearing the M50I mutation in combination with R263K and is selected in vitro by DTG treatment. 2019 Frontiers in microbiology Result HIV M50I;R263K 63;97 67;102 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. While mutation F121Y, in spite of being rarely selected in vivo, is capable of lowering RAL efficacy. 2019 Frontiers in microbiology Result HIV F121Y 15 20 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. While Y143R -a mutation in another of the three main resistance-related positions - is in cluster B. 2019 Frontiers in microbiology Result HIV Y143R 6 11 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A second drug-free control culture acquired the adjacent change of H219Q. 2019 PloS one Result HIV H219Q 67 72 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A similar selection experiment was performed with NL4-3 Gag P373S virus (and a 12 passage population) that also contained V370A, a substitution shown to affect bevirimat susceptibility. 2019 PloS one Result HIV P373S;V370A 60;122 65;127 Gag 56 59 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A364V was carried through the remaining passages, conferring >200-fold decreased susceptibility to GSK3532795. 2019 PloS one Result HIV A364V 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Additional emergent substitutions included two changes in the SP2/p6 cleavage site: P453S, co-selected at 100% with A364V after passage 2, and S495N that emerged by day 78 but did not increase beyond 20-30% over the course of 5 passages (45 days). 2019 PloS one Result HIV A364V;P453S;S495N 116;84;143 121;89;148 SP2;Gag 62;66 65;68 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. All viruses maintained the V370A site-directed mutation throughout the selection. 2019 PloS one Result HIV V370A 27 32 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Alternatively, the A364V mutation could modify the conformation of the nearby M367 side chain in a manner unfavorable for GSK3532795 binding. 2019 PloS one Result HIV A364V 19 24 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Among single amino acid substitutions and deletions representing major polymorphic variants and selected changes (Group 1, known MI substitutions) the change that engendered the greatest difference in GSK3532795 susceptibility resulted from A364V (>862-fold), which also conferred high level cross-resistance to bevirimat. 2019 PloS one Result HIV A364V 241 246 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. As shown (Table 4), the impact of the V362I mutation alone on GSK3532795 susceptibility was minimal, although combinations with secondary mutations R286, A326 or T332, resulted in higher levels of resistance. 2019 PloS one Result HIV V362I 38 43 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. As with the wild-type virus cultures, V218M emerged after 12 passages of V370A-containing virus in the absence of drug. 2019 PloS one Result HIV V218M;V370A 38;73 43;78 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. At passage 1 (after 13 days) V362I comprised 30% of the population. 2019 PloS one Result HIV V362I 27 34 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Based on the model, the 835-fold resistance observed for the A364V mutant is unlikely to arise from unfavorable contacts between the ligand and the residue 364 side chain in the mutant protein. 2019 PloS one Result HIV A364V 61 66 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. By passage 2 (35 days), this substitution was lost and stably replaced by A364V (100% of the population). 2019 PloS one Result HIV A364V 74 79 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. DeltaV370/T371A) virus was 74% as compared to 20% for DeltaV370 (Table 4). 2019 PloS one Result HIV T371A 10 15 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Finally, two additional substitutions emerged in the MA region: I34V appeared at passage 3 at 30% and gradually increased to 70%, until the selection was terminated on day 113, while V35I appeared transiently (~20%) between passages 7 and 9 and was then lost. 2019 PloS one Result HIV I34V;V35I 64;183 68;187 Matrix 53 55 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. For example, the replication capacity of NL4-3 V370A/DeltaT371 (a.k.a. 2019 PloS one Result HIV V370A 47 52 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. For the V370A-containing virus, sequences were obtained at each passage and treatment with increasing concentrations of GSK3532795 resulted in sequential accumulation of Gag substitutions (Table 2). 2019 PloS one Result HIV V370A 8 13 Gag 170 173 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Here, either WT NL4-3 P373S, or the same virus with site-directed mutants V370A and/or DeltaT371 were analyzed. 2019 PloS one Result HIV V370A 74 79 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. However, the addition of R286K, particularly in the context of triple changes, produced larger effects on susceptibility. 2019 PloS one Result HIV R286K 25 30 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. However, under these cell culture conditions, the secondary substitution H219Q rescued the reduced RC of V362I/V370A from 60% to 115% for the virus with the H219Q/V362I/V370A genotype (Table 4). 2019 PloS one Result HIV H219Q;V362I;V370A;H219Q;V362I;V370A 157;163;169;73;105;111 162;168;174;78;110;116 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. I34V has been described in a patient during PI therapy as a compensatory mutation, and may be acting in a similar capacity for GSK3532795. 2019 PloS one Result HIV I34V 0 4 PI 44 46 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In addition to these changes, the culture-adapted V370A-containing virus already had V218M as the majority population and this was maintained through all subsequent passages with or without GSK3532795. 2019 PloS one Result HIV V218M;V370A 85;50 90;55 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In addition, 2 participants (#s 2, 11) had V370V/L or V370M emerge and 1 participant (#106) had an emergent A366A/V (the latter along with an emergent A364A/V). 2019 PloS one Result HIV A364A;A364V;A366A;A366V;V370L;V370M;V370V 151;151;108;108;43;54;43 158;158;115;115;50;59;50 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In addition, one participant who lost a V370M mutation at Day 14 (#44; 40 mg dose group), susceptibility was significantly increased with a decrease in FC-IC50 from 132 at Day 10 to 0.48 at Day 14. 2019 PloS one Result HIV V370M 40 45 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In addition, V362V/I (2 participants, #s 1, 17) and V370V/I (participant # 13) or V370M (participant # 44) were lost in the Day 14 sample compared to the Day 10 sample from those participants. 2019 PloS one Result HIV V362I;V362V;V370I;V370M;V370V 13;13;52;82;52 20;20;59;87;59 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In all, 16 participants had 1 or more changes at Day 14 compared to Day 10 (at one or more amino acid positions 362, 364, 369-371), with 10 and 6 participants having A364A/V or V362V/I emerge (one participant had both emerge), respectively. 2019 PloS one Result HIV A364A;A364V;V362I;V362V 166;166;177;177 173;173;184;184 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In both the drug-free control passages, V218M emerged as the dominant population within 8 passages (not shown), suggesting this mutation is selected based upon improved fitness in cell culture, irrespective of MI treatment. 2019 PloS one Result HIV V218M 40 45 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In cultures of wild-type virus treated with GSK3532795, the emergence of I333V was observed, while in cultures of V370A-containing virus emergence of V362I occurred (in two cultures), with mixtures of H219H/Q and I333I/V in another set of V370A cultures. 2019 PloS one Result HIV H219H;H219Q;I333I;I333V;I333V;V362I;V370A;V370A 201;201;213;73;213;150;114;239 208;208;220;78;220;155;119;244 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In general, double combinations of changes with V362I or V370A (Group 3) had more modest effects on susceptibility to GSK3532795, with fold changes of 1.9 to 12. 2019 PloS one Result HIV V362I;V370A 48;57 53;62 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In non-B subtypes such single deletions are usually present in the context of V370A, with that change likely increasing fitness. 2019 PloS one Result HIV V370A 78 83 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In participants where Gag mutations were selected in addition to existing baseline polymorphisms, the baseline polymorphisms were either R286K or V370M/I or V370A. 2019 PloS one Result HIV R286K;V370A;V370I;V370M 137;157;146;146 142;162;153;153 Gag 22 25 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In the cases where phenotypic changes were seen in the absence of new treatment-emergent Gag substitutions, the baseline genotype showed a mixed population of Gag polymorphisms at positions V362 or V370 that was consolidated during treatment, for example, mixed V362V/I converting to V362I. 2019 PloS one Result HIV V362I;V362I;V362V 262;284;262 269;289;269 Gag;Gag 89;159 92;162 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In the first approach, NL4-3 Gag P373S virus was sequentially passaged beginning at a low concentration of GSK3532795 (either 1x or 2xEC50). 2019 PloS one Result HIV P373S 33 38 Gag 29 32 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In the other culture, V362I was selected with other substitutions in Gag (A118T, V218M, T332S) and Pr (R41G). 2019 PloS one Result HIV A118T;R41G;T332S;V218M;V362I 74;103;88;81;22 79;107;93;86;27 Gag;PR 69;99 72;101 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In the passages initiated with culture-adapted (p12) V370A-containing virus, a different pattern of substitutions was seen, with V362I dominating at passage 8 in both cultures, in one case accompanied by K114V in the MA and K14E in Pr, and in the other case by N235T (present at 50%) (Table 2). 2019 PloS one Result HIV K114V;K14E;N235T;V362I 204;224;261;129 209;228;266;134 Matrix;PR 217;232 219;234 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In the V370A virus passage, I333I/V and H219H/Q mixtures were consolidated to I333V, H219Q within the first passage; this variant grew steadily for further passages in the presence of increasing GSK532795 concentrations of up to 120xEC50. 2019 PloS one Result HIV H219H;H219Q;H219Q;I333I;I333V;I333V;V370A 40;40;85;28;28;78;7 47;47;90;35;35;83;12 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In three cultures, A364V became the dominant population and was selected with other Gag mutations (G221E, V159I, V218I, R286K and V362I). 2019 PloS one Result HIV A364V;G221E;R286K;V159I;V218I;V362I 19;99;120;106;113;130 24;104;125;111;118;135 Gag 84 87 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. It is plausible that the combination of the V362I mutation with changes at residues 326 or 332 negatively impacts interactions involving helix 10 and/or the proximal 352-356 beta-turn, which serve to stabilize the immature CA/SP1 assembly. 2019 PloS one Result HIV V362I 44 49 SP1;Capsid 226;223 229;225 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. One subject had H219H/P and another 2 had H219H/Q emerge at Day 10, with all 3 reverting back to H219 at Day 14. 2019 PloS one Result HIV H219H;H219H;H219P;H219Q 16;42;16;42 23;49;23;49 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Other emergent substitutions in the SP1 region included Q369Q/H in one subject (#22; 40 mg dose) and Delta371 in another (#43; 10 mg dose). 2019 PloS one Result HIV Q369H;Q369Q 56;56 63;63 SP1 36 39 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Secondary resistance polymorph R286K is somewhat more distant from V362. 2019 PloS one Result HIV R286K 31 36 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Starting with the double mutant V370A/DeltaT371, initial mixtures of A326A/T and V362V/I were replaced by two new substitutions, H219Q and A364V within three passages. 2019 PloS one Result HIV A326A;A326T;A364V;H219Q;V362I;V362V;V370A 69;69;139;129;81;81;32 76;76;144;134;88;88;37 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The deletion at amino acid 370 conferred a modest reduction in GSK3532795 susceptibility but substantially reduced RC to only 20%. 2019 PloS one Result HIV del aa370 4 30 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The differences in GSK3532795 susceptibility observed between the double V362I/V370A variant and the other V362I and V370A double and triple variants indicates that GSK3532795 susceptibility of V362I- and V370A-containing variants is context dependent. 2019 PloS one Result HIV V362I;V362I;V362I;V370A;V370A;V370A 73;107;194;79;117;205 78;112;199;84;122;210 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The double site-directed mutant, V370A/DeltaT371 selected for A326A/T and V362V/I at breakthrough. 2019 PloS one Result HIV A326A;A326T;V362I;V362V;V370A 62;62;74;74;33 69;69;81;81;38 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The most robust viruses in terms of growth were A364V and V370A, while V362I exhibited a lower RC. 2019 PloS one Result HIV A364V;V362I;V370A 48;71;58 53;76;63 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The only other change in a Day 14 sample was a reversion back to T371N (T371N was in the Baseline sample, DeltaT371 was in the Day 10 sample) in one participant (#43) (S2 Table). 2019 PloS one Result HIV DeltaT371;T371N;T371N 106;65;72 115;70;78 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. There appears to be volume available to accommodate the larger isoleucine side chain in the V362I mutant protein. 2019 PloS one Result HIV V362I 92 97 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. There is limited volume in this pocket, and replacement of the alanine side chain methyl group in the WT protein with the larger isopropyl moiety in the A364V resistance mutant may destabilize the six-helix bundle by preventing optimal engagement of the adjacent CA/SP1 monomers via steric blockade, thus increasing the rate of HIV protease cleavage and the rate of dissociation of bound GSK795, as previously reported. 2019 PloS one Result HIV A364V 153 158 PR;SP1;Capsid 332;266;263 340;269;265 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. These are A326T/DeltaV370 (29 -FC), R286K/V362I (61 -FC) and V362I/V370A (208 -FC). 2019 PloS one Result HIV A326T;R286K;V362I;V362I;V370A 10;36;42;61;67 15;41;47;66;72 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. These could be diminished slightly in the R286K mutant, but not enough to dramatically impact the overall stability of the CA/SP1 helix in the absence of additional destabilizing mutations. 2019 PloS one Result HIV R286K 42 47 SP1;Capsid 126;123 129;125 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. This suggests that any structural changes induced by the single V362I mutation are likely to be small. 2019 PloS one Result HIV V362I 64 69 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Thus, additional resistance selection experiments were performed with an expanded panel of Gag polymorphic variant viruses, including the single variants V362I, R286K, T332S, DeltaV370 or DeltaT371 and double variants V362I/V370A, R286K/V370A or T332S/V362I. 2019 PloS one Result HIV R286K;R286K;T332S;T332S;V362I;V362I;V362I;V370A;V370A 161;231;168;246;154;218;252;224;237 166;236;173;251;159;223;257;229;242 Gag 91 94 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Two of the three CA CTD secondary mutations (T332S, A326T) are either located in helix 10 (T332) or nearly within van der Waals contact distance of helix 10 residues (A326). 2019 PloS one Result HIV A326T;T332S 52;45 57;50 Capsid 17 19 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Two other participants had either H219H/P or H219H/Q at baseline, but also reverted to H219 at Day 10. 2019 PloS one Result HIV H219H;H219H;H219P;H219Q 34;45;34;45 41;52;41;52 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Two types of wild type NL4-3 Gag P373S virus were used; one was taken straight from the freezer and the other was first passaged 12 times in the absence of drug in order to increase the potential heterogeneity within the genome. 2019 PloS one Result HIV P373S 33 38 Gag 29 32 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V218M/A, H219Q, T239I in the CA N-terminal domain (CA-NTD) were also observed; T239I was present only transiently but the other two changes were fixed by the last passage. 2019 PloS one Result HIV H219Q;T239I;T239I;V218A;V218M 9;16;79;0;0 14;21;84;7;7 Capsid;Capsid 29;51 31;53 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. When polymorphic variants V370A, DeltaV370 or V362I were added to a subset of these (group 3), GSK3532795 susceptibility decreased 1.9-208 -fold. 2019 PloS one Result HIV V362I;V370A 46;26 51;31 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Where assessed, these double variants with larger reductions in susceptibility exhibited substantial reductions in RCs (41% RC for R286K/V362I and 60% RC for V362I/V370A) (Table 4). 2019 PloS one Result HIV R286K;V362I;V362I;V370A 131;137;158;164 136;142;163;169 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. Additional data regarding F99Y protein movement during TAMD simulations may be seen in the Supporting Information. 2019 The journal of physical chemistry. B Result HIV F99Y 26 30 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. Changes in DP behavior during F99Y-TAMD simulations indicate that an energetic barrier exists towards DP closure when a hydrophilic residue resides within the pocket. 2019 The journal of physical chemistry. B Result HIV F99Y 30 34 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. F99Y mutation affects conformational changes during substrate unbinding. 2019 The journal of physical chemistry. B Result HIV F99Y 0 4 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. F99Y-MD and F99Y-TAMD simulations of 20 ns were performed on the apo and substrate-bound states as outlined in Table 1. 2019 The journal of physical chemistry. B Result HIV F99Y;F99Y 12;0 16;4 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. F99Y-MD simulations indicate that the closed structures in substrate-bound and apo states are metastable similar to WT proteins. 2019 The journal of physical chemistry. B Result HIV F99Y 0 4 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. F99Y-TAMD simulations are performed in 10 independent replicas using the CV described in section to observe opening of the flaps and substrate unbinding. 2019 The journal of physical chemistry. B Result HIV F99Y 0 4 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. SMCV was performed on the F99Y mutant in a similar manner to WT. 2019 The journal of physical chemistry. B Result HIV F99Y 26 30 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. The differences between the F99Y mutant and WT are slight but expected. 2019 The journal of physical chemistry. B Result HIV F99Y 28 32 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. The DP's stabilize to a more open state in the beginning of the simulation around 12 A similar to the open state seen in F99Y - TAMDapo simulations. 2019 The journal of physical chemistry. B Result HIV F99Y 121 125 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. The initial string was produced by mutating F99Y for each image in the converged WT SMCV string with 100 ps of equilibration MD with CV's fixed. 2019 The journal of physical chemistry. B Result HIV F99Y 44 48 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. This research is in agreement with the F99Y mutation not increasing the free energy of flap opening and further suggests that the energetic cost associated with DP closure may be more conserved in the residues which close around the DP. 2019 The journal of physical chemistry. B Result HIV F99Y 39 43 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. While the transition from closed and bound to open flaps was an irreversible process with WT, a reformation of the apo bound state is observed with F99Y after substrate unbinding. 2019 The journal of physical chemistry. B Result HIV F99Y 148 152 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Additionally, although the output viral population was not sequenced, it is possible the Q577N sample regained replication fitness by reverting to WT during the course of the assay since it was not under the selective pressure of PIE12-trimer. 2019 Retrovirology Result HIV Q577N 89 94 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Because PIE12-trimer affinity is too tight to accurately measure via SPR, monomeric PIE12 was flowed over the IZN36 (WT and Q577R) surfaces. 2019 Retrovirology Result HIV Q577R 124 129 PI 84 86 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Crystal structure of PIE12 in complex with the Q577R mutation. 2019 Retrovirology Result HIV Q577R 47 52 PI 21 23 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Early analysis of a limited number of clones from the W2 resistant pool via Sanger sequencing identified the mutation Q577R within the gp41 hydrophobic pocket in all clones. 2019 Retrovirology Result HIV Q577R 118 123 gp41 135 139 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Here, to characterize the genetic basis of resistance and to understand the penetrance of the Q577R mutation, we deep sequenced the W1 and W2 viral pools, as well as a pNL4-3 control viral pool that had been propagated in the absence of inhibitors. 2019 Retrovirology Result HIV Q577R 94 99 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Importantly, starting viral titers of the Q577 mutant stocks (normalized to p24) vary significantly from WT, ranging from greatly reduced (~ 40-fold for Q577K and ~ 7-fold for Q577R) to increased (~ threefold for Q577N). 2019 Retrovirology Result HIV Q577K;Q577N;Q577R 153;213;176 158;218;181 p24 76 79 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. In addition to identifying the primary resistance mutation (Q577R/N/K) in the PIE12-trimer binding site, this analysis identified three gp120 and four gp41 mutations (Table 3 and. 2019 Retrovirology Result HIV Q577K;Q577N;Q577R 60;60;60 69;69;69 gp120;gp41 136;151 141;155 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. In an HXB2 pseudovirion, Q577R confers > 4000-fold resistance to PIE12-trimer. 2019 Retrovirology Result HIV Q577R 25 30 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Of the gp120 mutations, one is a point mutation (A48T), and two are in-frame deletions (Delta161-164 in the V1/V2 loop and Delta396-400 in the V4 loop). 2019 Retrovirology Result HIV A48T 49 53 gp120 7 12 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Only A48T lacked 100% penetrance and was found in 3/5 W1 and 3/8 W2 clones. 2019 Retrovirology Result HIV A48T 5 9 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577R and Q577K did not propagate significantly during the entire course of the assay, while Q577N replication was substantially delayed. 2019 Retrovirology Result HIV Q577K;Q577N;Q577R 10;93;0 15;98;5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577R disrupts these hydrogen bonds, likely accounting for the loss of affinity, and induces a repositioning of two adjacent residues (d-Glu9 in PIE12 and L581 in IQN17, although d-Glu9 position is variable in the WT structures). 2019 Retrovirology Result HIV Q577R 0 5 PI 145 147 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577R only requires a single nucleotide change, while Q577N requires a double mutation and likely occurs stepwise. 2019 Retrovirology Result HIV Q577N;Q577R 54;0 59;5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The Q577R mutation results in a dramatic (~ 65-fold) weakening of the interaction between PIE12-monomer and the hydrophobic pocket (Q577R KD = 2.0 microM vs. 2019 Retrovirology Result HIV Q577R;Q577R 4;132 9;138 PI 90 92 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. This search should identify mutations that compensate for the fitness defects associated with Q577R/N/K as well as those that contribute modestly to PIE12-trimer resistance, as W1 and W2 are slightly more resistant than the Q577 mutants alone. 2019 Retrovirology Result HIV Q577K;Q577N;Q577R 94;94;94 103;103;103 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. To determine the impact of Q577 mutation on PIE12 binding affinity, Q577R was incorporated into an N-peptide mimic (IZN36), and the interaction was analyzed via surface plasmon resonance (SPR). 2019 Retrovirology Result HIV Q577R 68 73 PI 44 46 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. To determine which pathway the virus took to acquire the Q577N substitution, we deep sequenced this N-trimer region from an intermediate pool of virus isolated at an earlier timepoint during resistance selection and noted an equal ratio of N (AAC) and K (AAG) (data not shown). 2019 Retrovirology Result HIV Q577N 57 62 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. To understand the molecular basis of Q577R-induced resistance, monomeric PIE12 was crystallized in complex with an HIV-1 N-trimer pocket mimic (IQN17) with the Q577R substitution, and the structure was determined at 1.3 A resolution (Table 2, PDB code 6PSA). 2019 Retrovirology Result HIV Q577R;Q577R 37;160 42;165 PI 73 75 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Two (Q550H and the silent V583V) are located within the RRE, L663F is in the gp41 membrane-proximal external region (MPER), and A823V is in the cytoplasmic domain between LLP-3 and LLP-1. 2019 Retrovirology Result HIV A823V;L663F;Q550H;V583V 128;61;5;26 133;66;11;31 gp41 77 81 31651864 HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. K103N/KN (155/372, 41.67%), V106M/MA/MV (107/372, 28.76%), G190A/AG/S (103/372, 27.69%), and Y181C/CY (89/372, 23.92%) were the major NNRTI-related mutations. 2019 Medicine Result HIV G190A;G190G;G190S;K103K;V106A;V106M;V106V;Y181C;Y181Y;K103N 59;59;59;0;28;28;28;93;93;0 69;69;69;8;39;39;39;100;101;7 NNRTI;Matrix 134;34 139;36 31651864 HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. M184V/I (236/372, 63.44%), K65KR/R (78/372, 20.97%), D67DN/N (77/372, 20.70%), and K70E/R/KR (72/372, 19.35%) were most common NRTI-related mutations. 2019 Medicine Result HIV D67D;D67N;K65K;K65R;K70E;K70K;K70R;M184I;M184V 53;53;27;27;83;83;83;0;0 60;60;34;34;92;92;92;7;7 NRTI 127 131 31651864 HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. The most common PI-related mutations were K20I/R (18/372, 4.84%) and V82I (13/372, 3.49%) (Table 3). 2019 Medicine Result HIV K20I;K20R;V82I 42;42;69 48;48;73 PI 16 18 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Among the 21 patients who experienced VF, 2 had 3 archived TAMs (D67N, K70R, and K219Q/E and M41L, K70R, and K219Q/E), including the M184V/I mutation. 2019 Open forum infectious diseases Result HIV D67N;K219E;K219E;K219Q;K219Q;K70R;K70R;M184I;M184V;M41L 65;81;109;81;109;71;99;133;133;93 69;88;116;88;116;75;103;140;140;97 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Among these, 17 (1.21%) patients had no previously detected M184V/I mutation and 4 (3%) did (Table 2). 2019 Open forum infectious diseases Result HIV M184I;M184V 60;60 67;67 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. At least 2 TAMs were documented in 42.3% of patients with M184V/I compared to 3.3% of those without the mutation (Supplementary Table S3). 2019 Open forum infectious diseases Result HIV M184I;M184V 58;58 65;65 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. In the IPW-adjusted analysis of 580 patients with prior VF, results for the primary and secondary outcomes were essentially unchanged, For the primary outcome, the estimated HR for patients with the M184V/I mutation was 1.27 (95% CI, 0.35-4.59; P = .733; Figure 1C) and for the composite outcome the estimated HR was 1.66 (95% CI, 0.81-3.43; P = .17). 2019 Open forum infectious diseases Result HIV M184I;M184V 199;199 206;206 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. In the univariate Cox proportional-hazards analyses, the presence of the M184V/I mutation was not significantly associated with a higher risk of failure (hazard ratio [HR], 1.81; 95% confidence interval [CI], 0.60-5.49; P = .29; Figure 1A). 2019 Open forum infectious diseases Result HIV M184I;M184V 73;73 80;80 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. In this subpopulation, 8 (1.8%) patients had no previous archived M184V/I mutation before IPW adjustment, while 4 (3.2%) did (Table 4). 2019 Open forum infectious diseases Result HIV M184I;M184V 66;66 73;73 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Most patients with a M184V/I mutation had experienced VF during their previous treatment history (127; 92.7%) compared with those without the mutation (453; 30.4%). 2019 Open forum infectious diseases Result HIV M184I;M184V 21;21 28;28 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. One patient had 2 TAMs (D67N and K219Q/E) without an archived M184V/I mutation. 2019 Open forum infectious diseases Result HIV D67N;K219E;K219Q;M184I;M184V 24;33;33;62;62 29;40;40;69;69 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Overall, 137 patients had an M184V/I mutation (8.4%) with a ratio of the presence or absence of the M184V/I mutation of approximately 1:11. 2019 Open forum infectious diseases Result HIV M184I;M184I;M184V;M184V 29;100;29;100 36;107;36;107 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Patients with M184V/I were predominantly male, with a mean age of 53.3 years. 2019 Open forum infectious diseases Result HIV M184I;M184V 14;14 21;21 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Seventy-five patients in total had a VB, of whom 63 (4.2%) were without and 12 (8.8%) had a M184V/I mutation (mean HIV-RNA level, 181 [92-269] and 267 [28-563], respectively). 2019 Open forum infectious diseases Result HIV M184I;M184V 92;92 99;99 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. The highest prevalence of the M184V/I mutation was found in the Aquitaine cohort (37 patients; 22.0%), followed by ARCA (14 patients; 15.9%), SHCS (56 patients; 7.2%), ATHENA (24 patients; 5.2%) and ICONA (6 patients; 4.5%). 2019 Open forum infectious diseases Result HIV M184I;M184V 30;30 37;37 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. The incidence of VF after the switch to ABC/3TC/DTG was 29.8 (11.2-79.4) and 13.6 (8.4-21.8) per 1000 person-years in patients with and without M184V/I, respectively. 2019 Open forum infectious diseases Result HIV M184I;M184V 144;144 151;151 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. The unweighted univariate analysis showed that M184V/I had an effect on the increase of the risk of the composite outcome (HR, 1.92; 95% CI, 1.09-3.35; P = .022; Figure 2A). 2019 Open forum infectious diseases Result HIV M184I;M184V 47;47 54;54 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. They had a longer duration of HIV infection, ART treatment, and a longer virological suppression before the switch to ABC/3TC/DTG compared with patients without the M184V/I mutation. 2019 Open forum infectious diseases Result HIV M184I;M184V 165;165 172;172 HIV infections 30 43 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. VF incidence was 32.0 (0.64-63.4) and 10.4 (0.21-20.60) for those with and without the M184V/I mutation, respectively. 2019 Open forum infectious diseases Result HIV M184I;M184V 87;87 94;94 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. VF or VBs, or both, were observed in 15 of 137 (10.95%) patients with a documented M184V/I mutation compared to 73 of 1489 (4.9%) patients in the group with a wild type at this position. 2019 Open forum infectious diseases Result HIV M184I;M184V 83;83 90;90 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. We did not observe any significant association between VF and the M184V/I mutation (data not shown). 2019 Open forum infectious diseases Result HIV M184I;M184V 66;66 73;73 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. It concerns a substitution of an arginine (R) by an isoleucine (I) at position 841 (R841I) in reference to HXB2 Env sequence numbering (Figure 5, Table 1). 2019 Viruses Result HIV R841I 84 89 Env 112 115 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. It consisted of an aspartic acid (D) substitution by a valine (V; D751V). 2019 Viruses Result HIV D751V 66 71 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The second was found in the Env signal peptide at position 24 and identifies a substitution of a methionine (M) by an Isoleucine (I; M24I; Figure 8). 2019 Viruses Result HIV M24I 133 137 Env 28 31 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The substitution of lysine (K) for isoleucine (I; K6I) in the Env SP at position six was highly enriched in chronic viruses, 79.04% (83/105) compared to TF viruses, 53.60% (52/97), OR = 3.26, 95% CI (1.76-6.02), p = 0.0001 using the chi-squared (Chi2) test. 2019 Viruses Result HIV K6I 50 53 Env 62 65 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. All three Nef-mediated downregulation functions were impaired in the mutant encoding both K94E and H116N, indicating that the impact of these polymorphisms can be additive. 2019 Cell reports Result HIV H116N;K94E 99;90 104;94 Nef 10 13 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Compared with parental NL4.3 Nef, K94E reduced HLA downregulation activity modestly (to 87%) (p < 0.05, unpaired Student's t test) but it had no effect on CD4 internalization. 2019 Cell reports Result HIV K94E 34 38 Nef 29 32 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Consistent with downregulation results, we observed lower SERINC5 surface expression on HEK293T cells producing wild-type NL4.3 compared with cells producing viruses that lacked Nef (DeltaNef) or those that encoded Nef mutations that were anticipated to be detrimental to this function (G2A, K94E, H116N, or K94E/H116N) (Figure 3A). 2019 Cell reports Result HIV G2A;H116N;H116N;K94E;K94E 287;298;313;292;308 290;303;318;296;312 Nef;Nef 178;215 181;218 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Consistent with results for NL4.3 Nef, reversion of E94K or N116H alone partially rescued SERINC5 downregulation activity (to 69% and 59%, respectively) (p < 0.05 for both); while reversion of both polymorphisms enhanced this activity further (to 89%) (p < 0.001). 2019 Cell reports Result HIV E94K;N116H 52;60 56;65 Nef 34 37 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Conversely, H116N reduced CD4 downregulation activity modestly (to 89%) (p < 0.05), but it had no effect on HLA internalization. 2019 Cell reports Result HIV H116N 12 17 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Empty vector and Nef G2A mutant were included as negative controls. 2019 Cell reports Result HIV G2A 21 24 Nef 17 20 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. In contrast to results obtained using NL4.3 Nef, the E94K and double reversion mutant displayed lower HLA downregulation activity compared with the primary Nef clone (56% and 51%, respectively) (p < 0.01), suggesting that unidentified compensatory polymorphisms in the EC48 nef sequence contributed to maintain this function. 2019 Cell reports Result HIV E94K 53 57 Nef;Nef;Nef 44;156;274 47;159;277 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. In contrast, K94E is selected more slowly in individuals expressing the non-protective B*08 allele and 94E is not the dominant variant observed for the FL8 epitope (at position 5 of FLKEKGGL) (rather K92R). 2019 Cell reports Result HIV K92R;K94E 200;13 204;17 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. In repeated assays, we observed no significant differences in replication capacity between NL4.3-derived viruses encoding wild-type Nef versus Nef K94E, H116N, or the double mutation in cells lacking SERINC5 (p > 0.05 for all). 2019 Cell reports Result HIV H116N;K94E 153;147 158;151 Nef;Nef 132;143 135;146 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. In repeated assays, we observed statistically significant delays in viral replication (measured as the slope of viral cell-to-cell spread over time) for viruses encoding Nef K94E, H116N, or the double mutation compared with wild-type NL4.3 (p < 0.05 for all). 2019 Cell reports Result HIV H116N;K94E 180;174 185;178 Nef 170 173 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. K94E and H116N Selectively Impair Nef-Mediated SERINC5 Downregulation Function. 2019 Cell reports Result HIV H116N;K94E 9;0 14;4 Nef 34 37 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Notably, H116N is often selected early following infection in individuals expressing the protective B*57 allele, and it is the predominant variant observed for the HW9 epitope (at position 1 of HTQGYFPDW). 2019 Cell reports Result HIV H116N 9 14 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Notably, NL4.3-derived viruses encoding Nef K94E, H116N, or the double mutation also displayed reduced infectivity when they passaged using primary peripheral blood mononuclear cells (PBMCs) (Figure 3C), indicating that these polymorphisms altered viral phenotypes in the presence of endogenous levels of SERINC5. 2019 Cell reports Result HIV H116N;K94E 50;44 55;48 Nef 40 43 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Notably, three Nef polymorphisms that were associated with a substantial reduction in SERINC5 downregulation function, I43V (-49% activity), K94E (-38%), and H116N (-14%) (Table 1), are viral "escape mutations" selected in CD8+ T cell epitopes restricted by HLA-C*03, B*08, and B*57, respectively. 2019 Cell reports Result HIV H116N;I43V;K94E 158;119;141 163;123;145 Nef 15 18 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Results from repeated assays were consistent with our prior observations, indicating that viruses encoding Nef K94E, H116N, or the double mutation displayed significantly lower replication capacity in primary cells compared with wild-type NL4.3 (p < 0.01 for all). 2019 Cell reports Result HIV H116N;K94E 117;111 122;115 Nef 107 110 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Specifically, DeltaNef virus was 41-fold less infectious compared with wild-type NL4.3, while G2A, K94E, H116N, and double-mutation viruses were 11-, 4-, 3-, and 5.5-fold less infectious than NL4.3, respectively (Figure 3B, black bars) (p < 0.05 for all, unpaired Student's t test). 2019 Cell reports Result HIV G2A;H116N;K94E 94;105;99 97;110;103 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Specifically, downregulation function was increased modestly for N51T, I114V, and S163C mutants, each of which displayed ~5% higher activity compared with parental Nef; whereas downregulation was impaired for C55S, K94E, H116N, V148L, and S163R mutants, each of which displayed 5%-50% lower activity compared with parental Nef. 2019 Cell reports Result HIV C55S;H116N;I114V;K94E;N51T;S163C;S163R;V148L 209;221;71;215;65;82;239;228 213;226;76;219;69;87;244;233 Nef;Nef 164;323 167;326 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. To assess the impact of K94E and H116N on viral phenotypes, we generated HIV-1 NL4.3-derived strains encoding these mutations in the absence or presence of SERINC5. 2019 Cell reports Result HIV H116N;K94E 33;24 38;28 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. To determine if the effect of K94E or H116N on SERINC5 downregulation was selective, we next tested the ability of Nef mutants encoding these substitutions to internalize CD4 and HLA class I (Figure 3G, left side). 2019 Cell reports Result HIV H116N;K94E 38;30 43;34 Nef 115 118 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Together, these results demonstrate that K94E and H116N reduce Nef's ability to downregulate SERINC5 to a greater extent compared with CD4 or HLA class I and further indicate that their impact on all three Nef functions may be modulated by other sequence variation present in primary nef alleles. 2019 Cell reports Result HIV H116N;K94E 50;41 55;45 Nef;Nef;Nef 63;206;284 66;209;287 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Together, these studies demonstrate that K94E and H116N impair viral infectivity and replication capacity in the presence of SERINC5. 2019 Cell reports Result HIV H116N;K94E 50;41 55;45 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. Viral Infectivity and Replication Capacity Are Impaired by K94E and H116N. 2019 Cell reports Result HIV H116N;K94E 68;59 73;63 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Considering that the anti-HIV-1 enzyme HDAC6 is a non-cell-surface protein, mainly expressed at cytoplasm, we first studied the degradation of HDAC6 in cells expressing a non-myristolated Nef mutant, Nef-G2A (Figure 3), which is unable to directly anchor to membranes. 2019 Frontiers in microbiology Result HIV G2A 204 207 Nef;Nef 188;200 191;203 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Despite its ability to target HDAC6, stabilizing Pr55Gag, virions obtained with the Nef-G2A mutant are poorly infectious (Figure 9C, HIV-1 infection capacity/Nef-G2A histogram). 2019 Frontiers in microbiology Result HIV G2A;G2A 88;162 91;165 Nef;Nef;PR 84;158;49 87;161;51 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. This Nef activity seems not to require its expression in membranes, since Nef-G2A mutant is fully active. 2019 Frontiers in microbiology Result HIV G2A 78 81 Nef;Nef 5;74 8;77 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. To further explore the potential regions on Nef involved in the interaction with HDAC6, we assayed a co-IP experiment in cells over-expressing the Nef-G2A or Nef-PPAA mutant together with HDAC6 (Figure 5A). 2019 Frontiers in microbiology Result HIV G2A 151 154 Nef;Nef;Nef 44;147;158 47;150;161 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. We also observed that HDAC6-mediated inhibition of virus production was neutralized by wt-Nef, Nef-G2A, and Nef-EA mutants (Figure 9C, viral production histograms). 2019 Frontiers in microbiology Result HIV G2A 99 102 Nef;Nef;Nef 90;95;108 93;98;111 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. We observe that wt-Nef and the Nef-G2A, but not the Nef-PPAA mutant, efficiently abrogate HDAC6-mediated Pr55Gag and Vif degradation (Figure 9A; quantified in Figure 9B). 2019 Frontiers in microbiology Result HIV G2A 35 38 Nef;Nef;Nef;Vif;PR 19;31;52;117;105 22;34;55;120;107 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. We observed that Nef-G2A-EGFP promotes HDAC6 degradation to a similar extent that wt-Nef-EGFP does (Figure 3A, quantified in Figure 3B). 2019 Frontiers in microbiology Result HIV G2A 21 24 Nef;Nef 17;85 20;88 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. We observed that wt-Nef and Nef-G2A specifically co-immunoprecipitate with HA-wt-HDAC6, while the Nef-PPAA mutant showed a reduced interaction with the deacetylase (Figure 5B, alpha-EGFP co-IP). 2019 Frontiers in microbiology Result HIV G2A 32 35 Nef;Nef;Nef 20;28;98 23;31;101 31745412 HIV Drug Resistance among Patients Failing Therapy at a Tertiary Center in Oman: A Case Record Review. The most common mutations were M184V/I (45; 53.6%), K103N/S (41; 48.8%), and G190A/S/E (20; 23.8%). 2019 Oman medical journal Result HIV G190A;G190E;G190S;K103N;K103S;M184I;M184V 77;77;77;52;52;31;31 86;86;86;59;59;38;38 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. Eleven (25%, 11/44) of the RTRM were thymidine analogue mutations (T215FY [2.5%, 6/239], K70R [1.7%, 4/239] and 0.8% (2/239) each of D67N, L210W, M41L, and K219Q/E (Fig 2). 2019 PloS one Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 133;156;156;89;139;146;67;67 137;163;163;93;144;150;74;74 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. M184V (8.4%, 20/239) and K103N (5.4%, 13/239) were the most frequent NRTI- and NNRTI-associated mutations respectively. 2019 PloS one Result HIV K103N;M184V 25;0 30;5 NNRTI;NRTI 79;69 84;73 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. Major protease inhibitor mutations were present in 3 (1.3%, 95% CI: 0.3-3.6%) of the sequences occurring as I54T-V82A, M46I and M46LV. 2019 PloS one Result HIV I54T;M46I;M46L;M46V;V82A 108;119;128;128;113 112;123;133;133;117 PR 6 14 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. Minor PI mutations were present in 27.6% (66/239) of the sequences with L10I/V being the most prevalent (22.2%) mutation followed by V11I (4.6%) and E35G (2.5%). 2019 PloS one Result HIV E35G;L10I;L10V;V11I 149;72;72;133 153;78;78;137 PI 6 8 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. Mutations M46I and M46LV demonstrated potential low-level resistance to saquinavir, indinavir, fosamprenavir, lopinavir and atazanavir (Fig 3). 2019 PloS one Result HIV M46I;M46L;M46V 10;19;19 14;24;24 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. The most common patterns among ART-experience patients were K103N only or in combination with P225H or V106A (9.8%, 4/41), Y181C only or in combination with V108I (9.0%, 4/41) and V179E (4.9%, 2/41). 2019 PloS one Result HIV K103N;P225H;V106A;V108I;V179E;Y181C 60;94;103;157;180;123 65;99;108;162;185;128 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. The most frequent pattern was M184V only (36%, 9/25) resulting in HLR to lamivudine/emtricitabine, low-level resistance (LLR) to abacavir and potential low-level resistance (PLR) to didanosine. 2019 PloS one Result HIV M184V 30 35 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. The most resistance NNRTI-associated pattern was G190A-Y181C which showed HLR to all the drugs in the class and this was from an ART-naive patient (Table 3). 2019 PloS one Result HIV G190A;Y181C 49;55 54;60 NNRTI 20 25 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. The mutational pattern, D67N-M41L-M184V-L210W-T215F/Y was the most resistant conferring HLR to all drugs in the class, except tenofovir that showed intermediate resistance (IR) (Table 2). 2019 PloS one Result HIV D67N;L210W;M184V;M41L;T215F;T215Y 24;40;34;29;46;46 28;45;39;33;53;53 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. The sequence with the non-polymorphic PI-selected mutations (I54T and V82A) confers HLR to nelfinavir and intermediate resistance to all other PI drugs except darunavir. 2019 PloS one Result HIV I54T;V82A 61;70 66;74 PI;PI 38;143 40;145 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. According to the Stanford Genotypic Resistance Interpretation Algorithm, v8.8 all TDR mutations that we identified were clinically relevant except mutation T69D, while the International AIDS Society (IAS) list confirmed nearly all mutations, except T215S, K219R, G190E and G140A, as clinically relevant. 2019 Scientific reports Result HIV G140A;G190E;K219R;T215S;T69D 273;263;256;249;156 278;268;261;254;160 AIDS 186 190 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Also, one Croatian patient with a complex pattern of resistance (SDRM to PI: I84V + NRTI: M184MIV, T215S, L210W + NNRTI: K101E, Y181C, G190A, P225PH) was observed in a transmission pair with a Serbian sequence with a similar SDRM pattern with one additional SDRM (PI: M46I), indicating cross border transmission of multi-class drug resistance. 2019 Scientific reports Result HIV G190A;I84V;K101E;L210W;M184I;M184M;M184V;M46I;P225H;P225P;T215S;Y181C 135;77;121;106;90;90;90;268;142;142;99;128 140;81;126;111;97;97;97;272;148;148;104;133 NNRTI;NRTI;PI;PI 114;84;73;264 119;88;75;266 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Cluster 12, with the SDRM T215S + L210W, appearing as a sub-cluster within Cluster 2, emerged at a more recent time, with its progenitor dated to the year 2009 (95% HPD, 2006.6-2011.5). 2019 Scientific reports Result HIV L210W;T215S 34;26 39;31 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Forward transmission of SDRMs throughout the period 2014-2017 was determined in several TCs: (1) T215S (n = 20) and its sub-cluster T215S + L210W (n = 9) (2), K101E (n = 14) and (3) V32I + I47V + T215D/E + L100I + K103N (n = 8). 2019 Scientific reports Result HIV I47V;K101E;K103N;L100I;L210W;T215D;T215E;T215S 189;159;214;206;140;196;196;132 193;164;219;211;145;203;203;137 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Furthermore, analysis of the integrase region revealed 3 accessory resistance mutations (T97A, Q146QH, D232N). 2019 Scientific reports Result HIV D232N;Q146H;Q146Q;T97A 103;95;95;89 108;101;101;93 IN 29 38 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. In 4/6 samples complete divergence was determined in samples in which DS detected T215S mutation at frequencies below the SS threshold (around 10%). 2019 Scientific reports Result HIV T215S 82 87 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Resistance to integrase strand-transfer inhibitors (InSTIs) was detected in single person, G140A, 1% (1/100). 2019 Scientific reports Result HIV G140A 91 96 IN;INSTI 14;52 23;58 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Resistance to NNRTIs was determined in 27/403 (6.7%) cases, with mutations K101E (3.7%), K103N (2.5%) and L100I (1.9%) most frequently observed. 2019 Scientific reports Result HIV K101E;K103N;L100I 75;89;106 80;94;111 NNRTI 14 20 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Resistance to PIs was detected in 10/403 (2.5%) persons, most often due to mutations V32I (1.9%) and I47V (1.9%). 2019 Scientific reports Result HIV I47V;V32I 101;85 105;89 PI 14 17 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Some of these sequences carrying SDRMs: T69D, G190E, K219Q and K219R + M41L belonged to large TCs (Table 3), others were not part of TCs, such as SDRMs K103N, G140A, G190A and M41L + T215D, while the sequence with SDRMs T215D + L210W formed a transmission pair with a Croatian sequence from the previous dataset (2006-2008) that carried the same resistance pattern. 2019 Scientific reports Result HIV G140A;G190A;G190E;K103N;K219Q;K219R;L210W;M41L;M41L;T215D;T215D;T69D 159;166;46;152;53;63;228;71;176;183;220;40 164;171;51;157;58;68;233;75;180;188;225;44 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The Croatian sequences contained the SDRM pattern PI: V32I, I47V + NRTI: T215E/D + NNRTI: L100I, K103N. 2019 Scientific reports Result HIV I47V;K103N;L100I;T215D;T215E;V32I 60;97;90;73;73;54 64;102;95;80;80;58 NNRTI;NRTI;PI 83;67;50 88;71;52 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The most common SDRM determined in the previous dataset (2006-2008), T215S, remained the most common SDRM in the newly studied period; specifically, 53 sequences from the previous and the new datasets formed one TC. 2019 Scientific reports Result HIV T215S 69 74 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The most frequent NRTI mutations were: T215S (7.4%), L210W (2.7%), T215D (1.7%) and M41L (1.2%). 2019 Scientific reports Result HIV L210W;M41L;T215D;T215S 53;84;67;39 58;88;72;44 NRTI 18 22 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The root node of Cluster 8, carrying the SDRM K101E, dated to the year 2008 (95% HPD, 2005.8-2011.6) and Cluster 10, responsible for the transmission of triple class drug resistance in Croatia, appeared to have originated in the year 2008 (95% HPD, 2005.9-2010.6). 2019 Scientific reports Result HIV K101E 46 51 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The sequence originating from the UK had a similar mutation pattern with additional SDRMs (PI: M46L, V82A and NRTI: T215Y). 2019 Scientific reports Result HIV M46L;T215Y;V82A 95;116;101 99;121;105 NRTI;PI 110;91 114;93 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Within this TC, a sub-cluster with SDRMs T215S + L210W expanded during the time frame of the new dataset (2014-2017). 2019 Scientific reports Result HIV L210W;T215S 49;41 54;46 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. A trans-dominant NES mutant of Rev termed M10 (L78D-E79L) cannot bind to Crm-1 and therefore makes HIV-1 Rev nonfunctional. 2020 Virology Result HIV E79L;L78D 52;47 56;51 Rev;Rev 31;105 34;108 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Agno lost its predominant cytoplasmic distribution pattern and became a more nuclear protein when mutations were made within its NES (L33D + E34L) 2020 Virology Result HIV E34L;L33D 141;134 145;139 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Agno lost its predominant cytoplasmic distribution pattern and became a more nuclear protein when mutations were made within its NES (L33D + E34L). 2020 Virology Result HIV E34L;L33D 141;134 145;139 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. In order to provide further evidence that this interaction is specific, we utilized a specific mutant of Agno (L33D + E34L) in JCV infection assays. 2020 Virology Result HIV E34L;L33D 118;111 122;116 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. Note that, the quality and amount of GST-Agno WT and GST-Agno mutant (L33D + E34L) proteins used in the experiments were highly similar. 2020 Virology Result HIV E34L;L33D 77;70 81;75 31765920 A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs. We have previously reported the negative effect of both E34A and L33A single mutants on the viral replication cycle. 2020 Virology Result HIV E34A;L33A 56;65 60;69 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. A previous study reported that L74I can restore replication to a virus with the K65R mutation without conferring drug resistance; therefore, we sought to test the hypothesis that L74I could restore replication "fitness" to a M184V mutant virus, thereby explaining the higher than expected VLs. 2020 The Journal of infectious diseases Result HIV K65R;L74I;L74I;M184V 80;31;179;225 84;35;183;230 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. After statistical adjustment for other mutations independently associated with increased VL, M184I/V was no longer significantly associated with VL failure. 2020 The Journal of infectious diseases Result HIV M184I;M184V 93;93 100;100 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. All participants were on TDF, most of them were also treated with EFV (75.2%) and 3TC (64.5%), and participants harboring M184I/V-mutated virus were significantly more likely to have high-level tenofovir and NNRTI resistance (Table 2). 2020 The Journal of infectious diseases Result HIV M184I;M184V 122;122 129;129 NNRTI 208 213 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Among 2873 participants included in the initial group, 1445 from 32 study groups across 15 countries had an available failure VL measurement, and M184I/V was present in 817 (56.5%) of these (Table 1 and Supplementary Table 1). 2020 The Journal of infectious diseases Result HIV M184I;M184V 146;146 153;153 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Between baseline and treatment failure, CD4 count increased to a similar extent in patients with and without M184I/V (median increase, 79 vs 48 cells/mm3; P = .55). 2020 The Journal of infectious diseases Result HIV M184I;M184V 109;109 116;116 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. CD4 count at VF was also lower in patients with M184V/I than those without (Figure 3). 2020 The Journal of infectious diseases Result HIV M184I;M184V 48;48 55;55 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Figure 4 shows mutations with strong evidence of an association with M184I/V. 2020 The Journal of infectious diseases Result HIV M184I;M184V 69;69 76;76 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. However, the estimated difference and 95% CI (0.09; 95% CI, -.01 to .20) excluded any meaningful decrease in VL failure associated with M184I/V. 2020 The Journal of infectious diseases Result HIV M184I;M184V 136;136 143;143 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. However, we did not assess the impact of M184I. 2020 The Journal of infectious diseases Result HIV M184I 41 46 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. In a crude comparison of VL failure, patients with M184I/V present had a higher median log10 VL (4.7; interquartile range [IQR], 3.4-5) than patients without M184I/V (median 4.3; IQR, 4.1-5.3). 2020 The Journal of infectious diseases Result HIV M184I;M184I;M184V;M184V 51;158;51;158 58;165;58;165 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. L74I was observed in 11.7% of subtype C-infected participants with M184I/V at VF and in 14.4% of CRF01_AE participants with M184I/V at VF (Supplementary Table 2). 2020 The Journal of infectious diseases Result HIV M184I;M184I;M184V;M184V;L74I 67;124;67;124;0 74;131;74;131;4 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Many of these mutations have previously been associated with drug resistance to tenofovir, either directly (K65R, K70E) or as compensatory mutations for K65R (A62V, S68N, F155Y). 2020 The Journal of infectious diseases Result HIV A62V;F155Y;K65R;K65R;K70E;S68N 159;171;108;153;114;165 163;176;112;157;118;169 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Mean baseline CD4 was significantly lower among patients who went on to develop M184I/V by treatment failure compared with those who did not (88 vs 180, P < .0001). 2020 The Journal of infectious diseases Result HIV M184I;M184V 80;80 87;87 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Molecular characterization of virus with the mutations M184V and L74I was undertaken. 2020 The Journal of infectious diseases Result HIV L74I;M184V 65;55 69;60 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Mutation of M184V back to M, leaving a virus with only L74I, had no impact on RT efficiency and a minor effect on infectivity (Figure 5B and C, compare left and right bars). 2020 The Journal of infectious diseases Result HIV L74I;M184V 55;12 59;17 RT 78 80 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Of note, L74I was the only mutation to be exclusively associated with M184V/I, occurring in 83 (10.2%) of patients with M184I/V, but not in 628 patients in which M184I/V was absent (P for association <.0001). 2020 The Journal of infectious diseases Result HIV L74I;M184I;M184I;M184I;M184V;M184V;M184V 9;70;120;162;70;120;162 13;77;127;169;77;127;169 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Participants harboring M184I/V were also more likely to have multiple NNRTI mutations. 2020 The Journal of infectious diseases Result HIV M184I;M184V 23;23 30;30 NNRTI 70 75 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Site-directed mutagenesis was performed to revert isoleucine back to leucine at 74 and revert valine to methionine at 184 (Figure 5A). 2020 The Journal of infectious diseases Result HIV V184M 94 122 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. The following NNRTI mutations were also associated: A98G, L100I, K103R, V108I, Y181C, Y188L, G190A, P225H, L228R, and M230L. 2020 The Journal of infectious diseases Result HIV A98G;G190A;K103R;L100I;L228R;M230L;P225H;V108I;Y181C;Y188L 52;93;65;58;107;118;100;72;79;86 56;98;70;63;112;123;105;77;84;91 NNRTI 14 19 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. The viral isolate tested also had NNRTI resistance mutations A98G, K103N, and P225H. 2020 The Journal of infectious diseases Result HIV A98G;K103N;P225H 61;67;78 65;72;83 NNRTI 34 39 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. There was no evidence that relationship between M184I/V and VL failure was modified by choice of NRTI, choice of NNRTI, or drug resistance to NNRTI or tenofovir (Figure 2). 2020 The Journal of infectious diseases Result HIV M184I;M184V 48;48 55;55 NNRTI;NNRTI;NRTI 113;142;97 118;147;101 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We found that removing the L74I mutation significantly decreased the efficiency of reverse transcription (Figure 5B, compare left bar with middle bar), whereas virus abundance was not affected, as determined by Western blot of viral p24 abundance in supernatants (Figure 5B, bottom panel). 2020 The Journal of infectious diseases Result HIV L74I 27 31 RT;p24 83;233 104;236 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We looked for associations in the dataset between M184V/I and RT amino acid positions known to be associated with drug exposure. 2020 The Journal of infectious diseases Result HIV M184I;M184V 50;50 57;57 RT 62 64 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We next explored the relationship between detection of M184I/V failure and CD4 count, noting that the duration of VF was likely longer in LMIC regions. 2020 The Journal of infectious diseases Result HIV M184I;M184V 55;55 62;62 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We then examined NRTI mutations associated with M184V/I that might play a compensatory role for M184I/V. 2020 The Journal of infectious diseases Result HIV M184I;M184I;M184V;M184V 48;96;48;96 55;103;55;103 NRTI 17 21 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. When within-study differences were pooled across studies, there was a marginally higher VL in patients with M184I/V present compared with absent (pooled difference in log10 VL, 0.18; 95% confidence interval [CI], .05-.31) (Figure 2). 2020 The Journal of infectious diseases Result HIV M184I;M184V 108;108 115;115 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. Among the 119 NNRTI mutations identified, the most common mutation was K103N (45.5%), which can cause a high level of resistance to efavirenz (EFV) and nevirapine (NVP), the two ARV drugs that are the components of the WHO-recommended first-line regimens. 2019 Current HIV research Result HIV K103N 71 76 NNRTI 14 19 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. Among them, the most common drug resistance mutation was K103N, and a total of 12 HIV infection patients contained this drug resistance mutation and were distributed in 10 transmission clusters. 2019 Current HIV research Result HIV K103N 57 62 HIV infections 82 95 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. From 2016 to 2018, most of the clusters containing drug resistance mutations did not show rapid growth within the cluster, but one cluster formed in 2017 contained three HIV-infected people carrying E138Q and V179D drug resistance mutations. 2019 Current HIV research Result HIV E138Q;V179D 199;209 204;214 HIV infections 170 182 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. In 2018, this cluster grew to contain 7 HIV-infected people, and five of them harbored the E138Q and V179D drug resistance mutations. 2019 Current HIV research Result HIV E138Q;V179D 91;101 96;106 HIV infections 40 52 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. In addition, 8 PI mutations were identified, of which the most common were I54V (1.5%) and V82A/I (1.5%), which can lead to resistance to darunavir (DRV), lopinavir (LPV) and atazanavir (ATV). 2019 Current HIV research Result HIV I54V;V82A;V82I 75;91;91 79;97;97 PI 15 17 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. The other two cases also contained the V179D locus but resulted only in potential resistance to EFV and NVP. 2019 Current HIV research Result HIV V179D 39 44 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. These five cases contained the E138Q and V179D resistance mutations, leading to low-level resistance to EFV and NVP. 2019 Current HIV research Result HIV E138Q;V179D 31;41 36;46 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. Thirty-one NRTI mutations were identified, of which the most common were M184L/V (9.1%) and K70R/E (9.1%). 2019 Current HIV research Result HIV K70E;K70R;M184L;M184V 92;92;73;73 98;98;80;80 NRTI 11 15 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Analysis on the thermal stability of 6HB showed that E560K increased the Tm ( Tm) by 6 C, but mutation E560D or E560G decreased the Tm ( Tm) by 3 C or 4 C, respectively, compared to wild-type N36. 2019 Retrovirology Result HIV E560D;E560G;E560K 104;113;53 109;118;58 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Based on these data, we speculated that the mutations E560K/D/G would alter Env conformations and lead to better exposure of MPER or extend the exposure time of gp41 MPER during virus entry. 2019 Retrovirology Result HIV E560D;E560G;E560K 54;54;54 63;63;63 gp41;Env 161;76 165;79 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Because the LAI Envs with E560D/G mutations emerged under T20 selection in vitro (our unpublished data) and three mutations E560K/D/G were reported under treatment of T20 in clinical data, the sensitivity of all mutants to T20 was examined. 2019 Retrovirology Result HIV E560D;E560D;E560G;E560G;E560K 124;26;124;26;124 133;33;133;33;133 Env 16 20 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Effects of Mutations E560K/D/G on HR1 peptide resistance. 2019 Retrovirology Result HIV E560D;E560G;E560K 21;21;21 30;30;30 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. IC50 values of the mutants with E560K/D/G generally reduced approximately 2.81- to 37.31-folds to 2F5 and 3.78- to 147.06-folds to 4E10, respectively, compared to that of wild type. 2019 Retrovirology Result HIV E560D;E560G;E560K 32;32;32 41;41;41 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Interestingly, we found that only mutant E560G showed dramatic sensitivity to T20, while IC50 values of the mutants with E560G and either L544S or G547D increased by 21.73- and 12.68-folds, respectively. 2019 Retrovirology Result HIV E560G;E560G;G547D;L544S 41;121;147;138 46;126;152;143 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. It is consistent with our previous finding that the E560K mutation derived from HIV-1 under selections of N peptide inhibitors in vitro. 2019 Retrovirology Result HIV E560K 52 57 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. It raised the possibility that these mutations are assistant mutations and could strengthen the effect of resistance when the founding resistance mutations such as L544S and G546D are present (Table 2). 2019 Retrovirology Result HIV G546D;L544S 174;164 179;169 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Mutations E560K/D/G alter sensitivity to inhibition by T20 and sCD4. 2019 Retrovirology Result HIV E560D;E560G;E560K 10;10;10 19;19;19 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Mutations E560K/D/G confer sensitivity to bNAbs 2F5 and 4E10. 2019 Retrovirology Result HIV E560D;E560G;E560K 10;10;10 19;19;19 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Pseudoviruses with mutation E560K or E560D had higher infectivity but pseudovirus with mutation E560G had lower infectivity compared to that of the wild type in RC4 cells that express lower levels of CD4 receptors (Additional file 1. 2019 Retrovirology Result HIV E560D;E560G;E560K 37;96;28 42;101;33 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. S1), implicating both mutants E560K and E560D may be also responsible for adaptation to the low levels of CD4 receptors which were used for selections of all resistance viruses. 2019 Retrovirology Result HIV E560D;E560K 40;30 45;35 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Surprisingly, the mutant containing L544S, G547D, E560G and the mutant containing L544S, G547D, E560D dramatically increased resistance activity with IC50 values enhanced by 555.16- and 224.18-folds (Table 2). 2019 Retrovirology Result HIV E560D;E560G;G547D;G547D;L544S;L544S 96;50;43;89;36;82 101;55;48;94;41;87 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The bands of 6HB formed by C34 and N36 E560K or E560G migrated upward due to reduced negative charges. 2019 Retrovirology Result HIV E560G 48 53 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The helicity formed by C34 and each N36 E560D or E560G was lower than that of wild-type N36. 2019 Retrovirology Result HIV E560G 49 54 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The infectivity of pseudoviruses bearing Env with E560K, E560D or E560G was lower in U87CD4+CXCR4+ cells that express high levels of CD4 and CXCR4 receptors (Additional file 1. 2019 Retrovirology Result HIV E560D;E560G;E560K 57;66;50 62;71;55 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The mutation E560K conferred resistance to N36 and IZN36 and the IC50 values to both peptides were higher than that of wild type, while mutants with E560D and E560G were similar or more sensitive to N36 and IZN36 (Table 1. 2019 Retrovirology Result HIV E560D;E560G;E560K 149;159;13 154;164;18 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The results showed that the neutralization sensitivity of the mutants with E560K/D/G to 2F5 and 4E10 enhanced. 2019 Retrovirology Result HIV E560D;E560G;E560K 75;75;75 84;84;84 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The sensitivity of HIV-1 LAI wild type and mutants with E560K, E560D or E560G to HR1 peptide inhibitors were detected in RC4 cells. 2019 Retrovirology Result HIV E560D;E560G;E560K 63;72;56 68;77;61 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Therefore, we analyzed the T20-selected clones containing substitutions L544S, G547D, and E560G/D which appeared in above order in the selected cultures in vitro (our unpublished data). 2019 Retrovirology Result HIV E560D;E560G;G547D;L544S 90;90;79;72 97;97;84;77 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. These results indicated that mutations of E560G/D assisted the founding resistance mutations and enhanced resistance activity to T20. 2019 Retrovirology Result HIV E560D;E560G 42;42 49;49 31818716 Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial. CS detected an additional 7 individuals with mutations conferring drug resistance to etravirine only (E38AV; V90IV; E138A; V179T; A98AG, V179T; V179DV; and A98G), who were wild-type at OLA codons. 2020 The lancet. HIV Result HIV A98A;A98G;A98G;E138A;E38A;E38V;V179D;V179T;V179T;V179V;V90I;V90V 130;130;156;116;102;102;144;123;137;144;109;109 135;135;160;121;108;108;150;128;142;150;114;114 31818716 Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial. Testing by OLA detected and CS and/or NGS confirmed 122 mutations in 93 participants at enrollment across both study arms: 61 participants had only mutations conferring resistance to NNRTI, 15 had NNRTI resistance mutations and M184V conferring resistance to lamivudine, and one had M184V alone. 2020 The lancet. HIV Result HIV M184V;M184V 228;283 233;288 NNRTI;NNRTI 183;197 188;202 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Among all individuals sharing DRMs, 66/175 (38%) shared K103N/S involving 24 clusters (Figures 3a and 3b). 2020 The Journal of antimicrobial chemotherapy Result HIV K103N;K103S 56;56 63;63 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Among all persons sharing DRMs (n = 175), those sharing K103N were significantly younger (aOR per 1 year increase: 0.93, 0.88-0.98, P = 0.003), were less prone to belong to larger clusters (aOR per cluster size unit increase: 0.66, 0.53-0.82, P < 0.001) and were less frequent after 2016 (2017 aOR = 0.25, 0.08-0.80, P = 0.016) (Table 3). 2020 The Journal of antimicrobial chemotherapy Result HIV K103N 56 61 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Both M184V and M184I were observed mainly as low-frequency variants in approximately 0.6% of the participants. 2020 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 15;5 20;10 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Frequent NRTI DRMs included the thymidine analogue mutations M41L, L210W and T215S. 2020 The Journal of antimicrobial chemotherapy Result HIV L210W;M41L;T215S 67;61;77 72;65;82 NRTI 9 13 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. K103N was the most frequent surveillance DRM with 6.6% frequency (7.1% K103N/S) (Figure 1c). 2020 The Journal of antimicrobial chemotherapy Result HIV K103N;K103S;K103N 71;71;0 78;78;5 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. K65R was very rare and only observed as a low-frequency variant. 2020 The Journal of antimicrobial chemotherapy Result HIV K65R 0 4 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Other commonly observed NNRTI DRMs included G190A, Y188L, Y181C and K101E (Figure 1c). 2020 The Journal of antimicrobial chemotherapy Result HIV G190A;K101E;Y181C;Y188L 44;68;58;51 49;73;63;56 NNRTI 24 29 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Other frequently shared DRMs included: reverse transcriptase (RT) Y188L (11/175), RT T215S/C (24/175) and protease M46I (19/175), mostly at >=20% within-host frequency; and RT D67N/G/E (56/175) and RT P225H (16/175) as low-frequency variants. 2020 The Journal of antimicrobial chemotherapy Result HIV D67E;D67G;D67N;M46I;P225H;T215C;T215S;Y188L 176;176;176;115;201;85;85;64 184;184;184;119;206;92;92;71 RT;PR;RT;RT;RT;RT 39;106;62;82;173;198 60;114;64;84;175;200 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. The most frequent PI mutations included M46I/L and L90M. 2020 The Journal of antimicrobial chemotherapy Result HIV L90M;M46I;M46L 51;40;40 55;46;46 PI 18 20 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. Among the four patients with virologic failure, one developed two new resistance mutations (M184 V and N155H). 2019 BMC public health Result HIV M184V;N155H 92;103 99;108 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. Baseline resistance to at least one NNRTI was the most commonly observed resistance (with 12% of newly diagnosed asylum seekers exhibiting K103 N/S mutations; of these, 5/7 were from Latin America and 2/7 were from Africa), followed by NRTI resistance. 2019 BMC public health Result HIV K103N;K103S 139;139 147;147 NNRTI;NRTI 36;236 41;240 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. M184 V/I, K65R and TAMs were uncommon, as was multidrug resistance. 2019 BMC public health Result HIV K65R;M184I;M184V 10;0;0 14;8;8 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. One newly diagnosed patient, who was unknowingly prescribed functional monotherapy, developed full integrase inhibitor resistance (N155H, Q148R, S147G, E138K, and E92Q mutations). 2019 BMC public health Result HIV E138K;E92Q;N155H;Q148R;S147G 152;163;131;138;145 157;167;136;143;150 IN 99 108 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Alignment of RT-DNA and M184V-DNA structures resulted in an RMSD of 0.39 A. 2019 Communications biology Result HIV M184V 24 29 RT 13 15 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Although the calculated maximum likelihood coordinate error reported in Phenix refinement is 0.33 A for the WT and M184V (-)-FTC-TP structures, this shift is propagated to cause other atoms of (-)-FTC-TP to move more than 0.33 A from the WT structure. 2019 Communications biology Result HIV M184V 115 120 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. As expected, M184V incorporated dCTP (kp/Kd = 2.3 microM-1 s-1) with a similar efficiency to WT (kp/Kd = 1.9 microM-1 s-1) (Table 1). 2019 Communications biology Result HIV M184V 13 18 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. As in our previous work, single-turnover kinetic assays were performed by rapidly mixing a pre-incubating solution of 120 nM HIV-1 RT (WT or M184V) and 30 nM 5'-[32P]-labeled 18/26-mer dsDNA substrate (Methods) with varying concentrations of dCTP, or an active metabolite of NRTIs for different times, before being quenched by 0.37 M EDTA. 2019 Communications biology Result HIV M184V 141 146 NRTI;RT 275;131 280;133 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. As with the above-mentioned WT structures, the same procedure (Methods) was used to generate the ternary structure of M184V, DNA, and (-)-FTC-TP (M184V-DNA (-)-FTC-TP). 2019 Communications biology Result HIV M184V;M184V 118;146 123;151 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. As with WT RT, the crystal structure of M184V-DNA bound to dCTP (M184V-DNA dCTP) was determined. 2019 Communications biology Result HIV M184V;M184V 40;65 45;70 RT 11 13 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Comparing M184V-DNA to RT-DNA (PDB code 3KJV) in the same crystallography system. 2019 Communications biology Result HIV M184V 10 15 RT 23 25 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. However, the binding affinities of the M184V mutant for (-)-FTC-TP and (-)-3TC-TP were reduced (280-fold and 212-fold, respectively), compared to WT, whereas the kp values remain relatively unchanged. 2019 Communications biology Result HIV M184V 39 44 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Interestingly, (+)-FTC-TP (Kd = 1.8 +- 0.3 microM) and (+)-3TC-TP (Kd = 5.4 +- 1.2 microM) were bound more tightly to M184V than the (-)-analogs leading to relatively lower selectivity factors of 30 and 69, respectively. 2019 Communications biology Result HIV M184V 118 123 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Mechanistic basis of M184V resistance to L-nucleotide analogs. 2019 Communications biology Result HIV M184V 21 26 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Our pre-steady-state kinetic data support that M184V does not discriminate against dCTP based on similar kinetic parameters measured for both WT and M184V (Table 1). 2019 Communications biology Result HIV M184V;M184V 47;149 52;154 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Previous kinetic studies have aimed at understanding the efficiency of incorporation for (-)-FTC-TP or (-)-3TC-TP, how they compete against dCTP, and the effect of resistance mutations, such as M184V. 2019 Communications biology Result HIV M184V 194 199 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Representative kinetic plots displaying M184V-catalyzed incorporation of (-)-FTC-TP onto 18/26-mer dsDNA substrate are shown in. 2019 Communications biology Result HIV M184V 40 45 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Structure alignment through residues 107-112 and 151-215 in the p66 subunit between the WT and M184V structures with (-)-FTC-TP shows that the oxathiolane sulfur is shifted away from residue V184 by 0.3 A compared to M184. 2019 Communications biology Result HIV M184V 95 100 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The combination of a steric shift and altered triphosphate orientation likely results in reduced binding affinity of (-)-FTC-TP (280-fold higher Kd in Table 1) with M184V than with WT RT. 2019 Communications biology Result HIV M184V 165 170 RT 184 186 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The M184V mutation was introduced into both the p66 and p51 subunits of RT (Methods) and the crystal structure of the binary complex of RT M184V and DNA (M184V-DNA) was solved. 2019 Communications biology Result HIV M184V;M184V;M184V 4;139;154 9;144;159 RT;RT 72;136 74;138 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The overall binding conformation is nearly identical for RT-DNA dCTP and M184V-DNA dCTP. 2019 Communications biology Result HIV M184V 73 78 RT 57 59 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. There appears to be a small shift in the primer 3'-terminal nucleotide in response to the mutation which was also observed in the previous binary structure of M184I RT bound to DNA. 2019 Communications biology Result HIV M184I 159 164 RT 165 167 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. To understand the interaction of cytidine analog drugs with WT HIV-1 RT, crystal structures were determined by covalently cross-linking purified RT to an 18/26-mer dsDNA substrate (Methods) via an N2-cystamine-deoxyguanosine to Q258C present in the p66 subunit of RT. 2019 Communications biology Result HIV Q258C 228 233 RT;RT;RT 69;145;264 71;147;266 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. We determined the pre-steady-state kinetic parameters of maximal nucleotide incorporation rate constants (kp) and apparent equilibrium dissociation constants (Kd) for dCTP, (+)-FTC-TP, (-)-FTC-TP, (+)-3TC-TP and (-)-3TC-TP with WT or M184V HIV-1 RT (Table 1). 2019 Communications biology Result HIV M184V 234 239 RT 246 248 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. Based on this, we designed RT_A with M184V and K65R/N (RT_An) and RT_A with K103N and G190S (RT_Ann) which we predicted to have reduced polymerase and RNase H activities, respectively. 2019 Oxidative medicine and cellular longevity Result HIV G190S;K103N;K65N;K65R;M184V 86;76;47;47;37 91;81;53;53;42 Pol 136 146 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. G190S and K103N have little effect on RT-driven polymerization but selectively slow down RNase H cleavage and delay initiation of DNA synthesis, resulting in a significant reduction of viral replication competence. 2019 Oxidative medicine and cellular longevity Result HIV K103N;G190S 10;0 15;5 RT 38 40 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. It is present either alone or in combination with other mutations, such as K103N, and is never detected in HIV-1 patients naive to treatment with NNRTIs. 2019 Oxidative medicine and cellular longevity Result HIV K103N 75 80 NNRTI 146 152 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. Mutations M184V/K65R or K103N/G190S were introduced into p6HRT_A by site-directed mutagenesis, yielding plasmids for prokaryotic expression of RT_An and RT_Ann, respectively, to purify respective proteins and determine their enzymatic activities. 2019 Oxidative medicine and cellular longevity Result HIV G190S;K103N;K65R;M184V 30;24;16;10 35;29;20;15 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. The most frequent mutation of resistance to NRTI worldwide is M184V/I, followed by K65R/N, L74V/I, Y115F, and Q151M, and the most prevalent for FSU_A is M184V, followed by K65R/N. 2019 Oxidative medicine and cellular longevity Result HIV K65N;K65N;K65R;K65R;L74I;L74V;M184I;M184V;M184V;Q151M;Y115F 83;172;83;172;91;91;62;62;153;110;99 89;178;89;178;97;97;69;69;158;115;104 NRTI 44 48 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. The most frequent primary mutation of resistance to NNRTI worldwide is G190S (http://hivdb.stanford.edu/DR/NNRTIResiNote.html). 2019 Oxidative medicine and cellular longevity Result HIV G190S 71 76 NNRTI 52 57 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Adding M46I and I54V mutations to a RTV-resistant mutant was shown to improve catalytic efficiency while sustaining resistance. 2020 The FEBS journal Result HIV I54V;M46I 16;7 20;11 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. All three mutants utilize mutations in the hinge region at 35 and compensating M36I mutation to drive rearrangements of the hinge and alter its separation from the flap. 2020 The FEBS journal Result HIV M36I 79 83 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. All three resistant proteases have mutations for Glu35 (E35N or E35D) that break the ion pair with flap residue Arg57' and a compensating M36I. 2020 The FEBS journal Result HIV E35D;E35N;M36I 64;56;138 68;61;142 PR 20 29 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Another study on single mutants V32I, L33F, L76V, and L90M showed how remote mutations can impact inhibitor binding by altering protein ensemble dynamics through a rearranged network of residues circulating to the active site. 2020 The FEBS journal Result HIV L33F;L76V;L90M;V32I 38;44;54;32 42;48;58;36 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. As shown in Figure 4C, the smaller M36I residue in PRS5B structures retains significant van der Waals contacts with Ile15' and Leu38' and the mutated I33L sidechain due to a shift in its main chain. 2020 The FEBS journal Result HIV I33L;M36I 150;35 154;39 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. By allowing a continuation of van der Waals contacts at the hinge-Loop 1 interface using a shorter side chain, M36I counterbalances the effects of E35N and N83D and stabilizing the hinge-loop. 2020 The FEBS journal Result HIV E35N;M36I;N83D 147;111;156 151;115;160 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Comparison of both PRS5B/PI structures with analogous wild-type complexes reveals how G73T and A71V mutations act in synergy with other accessory mutations to drive structural shifts of almost 3 A in Loop 2 in both subunits. 2020 The FEBS journal Result HIV A71V;G73T 95;86 99;90 PI 25 27 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Comparison of the new PRS5B structures with equivalent PR, PRS17, and PR20 complexes illustrates how the additional mutation of N83D replaces direct hydrogen bonds with water-mediated interactions at the hinge-body interface. 2020 The FEBS journal Result HIV N83D 128 132 PR;PR;PR 55;59;70 57;61;72 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Comparison of the PRS5B/DRV hinge-region mutations with those in the DRV complexes with PRS17 and PR20 (Figures 4D and E) highlights the influence of the N83D mutation. 2020 The FEBS journal Result HIV N83D 154 158 PR;PR 88;98 90;100 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Coordinated substitutions of M36I and I33L maintain van der Waals contacts between the hinge and Loop 1, thus counteracting the loss of interactions of hinge with main chain of residue 21' and flaps in mutant. 2020 The FEBS journal Result HIV I33L;M36I 38;29 42;33 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. For PR with single substitution of L76V (PRL76V), two-fold increased susceptibility to denaturation by urea was accompanied by a 7-fold higher dimer dissociation constant (Kd) relative to wild-type enzyme, although the catalytic efficiency was unchanged. 2020 The FEBS journal Result HIV L76V 35 39 PR;PR 4;41 6;43 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. G73T is a rare minor drug resistance mutation for ATV. 2020 The FEBS journal Result HIV G73T 0 4 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Hinge cluster mutations E35N and M36I coordinate with N83D to disengage flaps. 2020 The FEBS journal Result HIV E35N;M36I;N83D 24;33;54 28;37;58 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. However, the addition of G73T combined with the other mutations in the cluster produces a more dramatic expansion of Loop 2 in PRS5B than seen in the two other drug-resistant mutants. 2020 The FEBS journal Result HIV G73T 25 29 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. I84V is the sole mutation in PRS5B with a side chain that faces the active site cavity. 2020 The FEBS journal Result HIV I84V 0 4 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. In addition, PRS5B bears the unique N83D mutation which leads to fewer interactions between flap and hinge than observed in both PRS17 and PR20. 2020 The FEBS journal Result HIV N83D 36 40 PR;PR 129;139 131;141 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. In PRS17/DRV, the E35D side chain forms an ion pair with K20R and a hydrogen bond with the side chain of Asn83'. 2020 The FEBS journal Result HIV E35D;K20R 18;57 22;61 PR 3 5 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. In PRS5B structures, the shorter sidechain of I54V decreases hydrophobic interactions with the Ile50 side chain on the opposite subunit. 2020 The FEBS journal Result HIV I54V 46 50 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. L10I and L63P did not show structural changes in PRS5B but have been shown to help maintain thermal stability when combined with I84V. 2020 The FEBS journal Result HIV I84V;L63P;L10I 129;9;0 133;13;4 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Larger hydrophobic residues from mutations L11I, V22I, and L24M are located deep within the hydrophobic core of the protease and near the main chain of catalytic Asp25/25'. 2020 The FEBS journal Result HIV L11I;L24M;V22I 43;59;49 47;63;53 PR;Asp 116;162 124;165 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Like PRS5B, PRS17 contains only one active site mutation, V82S, which does not significantly alter the size of the inhibitor binding site or interactions with DRV relative to those of wild-type PR/DRV but may contribute to substrate recognition when combined with the G48V flap mutation. 2020 The FEBS journal Result HIV G48V;V82S 268;58 272;62 PR;PR 12;194 14;196 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Local side chain disorder was observed near the mutations E35N and S37D in subunit A, likely due to lack of crystal contacts as observed for subunit B and the clusters of mutations leading to loss of interactions in this region. 2020 The FEBS journal Result HIV E35N;S37D 58;67 62;71 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. M46I and I54V mutations co-occur frequently in drug resistance. 2020 The FEBS journal Result HIV I54V;M46I 9;0 13;4 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. More importantly, the larger side chain of G73T induces a 180 flip in the bulky Leu89 side chain where the Cgamma atom is ~2.5 A from the position in PR. 2020 The FEBS journal Result HIV G73T 43 47 PR 151 153 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Mutation A71V is associated with resistance to all PIs except for DRV, APV and TPV, while G73T only shows significant resistance to ATV. 2020 The FEBS journal Result HIV A71V;G73T 9;90 13;94 PI 51 54 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Mutation clusters at the hinge and Loop 2 are linked via mutation E21D in Loop 1. 2020 The FEBS journal Result HIV E21D 66 70 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Mutation L10I in Loop 1 of PRS5B was excluded from the designated clusters due to absence of significant structural changes as also seen for the same mutation in the PRS17/DRV structure. 2020 The FEBS journal Result HIV L10I 9 13 PR 166 168 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Mutations A71V and G73T coordinate with accessory mutations L11I, A22V, L24M, and I62/64/66V to induce structural shifts in Loop 2. 2020 The FEBS journal Result HIV A22V;A71V;G73T;L11I;L24M 66;10;19;60;72 70;14;23;64;76 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Mutations E35N and N83D drive two alternate conformations for the main chain of the hinge-loop at residues 34' and 35' through decreased interactions with 80's loop and flap. 2020 The FEBS journal Result HIV E35N;N83D 10;19 14;23 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. N83D has long been identified as a major resistance associated mutation for TPV. 2020 The FEBS journal Result HIV N83D 0 4 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. N83D introduces a negatively charged carboxylate group and eliminates the hydrogen bonds with Glu34' side chain and with the backbone carbonyl oxygen of Glu21'. 2020 The FEBS journal Result HIV N83D 0 4 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Non-active-site mutations in this region, such as A71V and G73S, have been shown to propagate changes to the catalytic site and provide cross-resistance for inhibitors. 2020 The FEBS journal Result HIV A71V;G73S 50;59 54;63 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Only M36I is associated with resistance to ATV, IDV, NFV and TPV, while the other hinge mutations have no significant association with resistance. 2020 The FEBS journal Result HIV M36I 5 9 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PR20 also contains the active site mutation I84V, which works synergistically with 3 other mutations to substantially increase the size of the inhibitor binding cavity as shown by 2 A bigger distance between the closest atoms of Val47 and Val84 and thus decrease the affinity for PIs. 2020 The FEBS journal Result HIV I84V 44 48 PI;PR 280;0 283;2 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PR20 shows an expanded inhibitor binding cavity due to a cluster of mutations (D30N, V32I, I47V, and I84V). 2020 The FEBS journal Result HIV D30N;I47V;I84V;V32I 79;91;101;85 83;95;105;89 PR 0 2 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS17 and PR20 also have additional compensating mutations that act synergistically with M36I (K20R in PRS17 and I33F, I13V and I15V in PR20) to further stabilize the hinge. 2020 The FEBS journal Result HIV I13V;I15V;I33F;K20R;M36I 119;128;113;95;89 123;132;117;100;93 PR;PR;PR;PR 0;10;103;136 2;12;105;138 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS17 and PR20 also share the A71V mutation. 2020 The FEBS journal Result HIV A71V 30 34 PR;PR 0;10 2;12 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS17 contains a cluster of three flap mutations, M46L, G48V, and I54V, which primarily affect the conformation of the flaps. 2020 The FEBS journal Result HIV G48V;I54V;M46L 56;66;50 60;70;54 PR 0 2 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS5B contains 22 mutations, including only a single mutation (I84V) in the inhibitor binding site and two mutations (M46L and I54V) in the flaps. 2020 The FEBS journal Result HIV I54V;I84V;M46L 127;63;118 131;67;123 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS5B contains a second flap mutation M46I, which is a drug resistance mutation for all clinical PIs except DRV, SQV and TPV. 2020 The FEBS journal Result HIV M46I 38 42 PI 97 100 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS5B harbors 4 mutations in the hinge, E35N, M36I, S37D, and R41K. 2020 The FEBS journal Result HIV E35N;M36I;R41K;S37D 40;46;62;52 44;50;66;56 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS5B, with its unique N83D mutation, features two backbone conformations for a section of the hinge-loop, whereas PRS17 and PR20 contain additional compensating mutations in Loop 1 to stabilize the hinge. 2020 The FEBS journal Result HIV N83D 23 27 PR;PR 115;125 117;127 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. PRS5B's Loop 2 cluster facilitates more dramatic shifts compared to those in other mutants containing A71V, although three mutations serve to diminish these changes. 2020 The FEBS journal Result HIV A71V 102 106 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Structural analysis of PRS5B in complexes with APV and DRV demonstrates minor alteration in the inhibitor binding site, consistent with the presence of only I84V mutation. 2020 The FEBS journal Result HIV I84V 157 161 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The bulge in Loop 2 induced by G73T and A71V is offset by ~1 A due to smaller side chains in the I62V, I64V and I66V mutations, which have a compensatory effect (Figure 5C). 2020 The FEBS journal Result HIV A71V;G73T;I62V;I64V;I66V 40;31;97;103;112 44;35;101;107;116 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The coordinated effects of G73T, A71V, and flipped Leu89 conformation combine with clustered accessory mutations to bring about rearrangements in the Loop 2. 2020 The FEBS journal Result HIV A71V;G73T 33;27 37;31 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The flipped Leu89 side chain is directed toward the new bulkier side chain of the A71V mutation and retains hydrophobic contacts with the larger side chains of mutated Val71 and Thr73. 2020 The FEBS journal Result HIV A71V 82 86 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The hinge mutation M36I substitutes a shorter hydrophobic side chain. 2020 The FEBS journal Result HIV M36I 19 23 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The loss of charge due to the E35N mutation in PRS5B eliminates the ion pair in wild-type enzyme between the side chains of Glu35' and flap residue Arg57' (Figure 4A). 2020 The FEBS journal Result HIV E35N 30 34 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The polar side chain of G73T is stabilized by hydrogen bonds with the side chain of Glu92 in a shifted conformation. 2020 The FEBS journal Result HIV G73T 24 28 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The shorter E21D side chain in PRS5B mutant cannot form this hydrogen bond with Thr12' side chain. 2020 The FEBS journal Result HIV E21D 12 16 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The side chain atoms of mutated residue R41K show no electron density in both subunits. 2020 The FEBS journal Result HIV R41K 40 44 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The side chain of flap residue 46 is adjacent to Phe53 at the protein surface, however, the shorter hydrophobic side chain of M46I shows no significant effects on the flap structure of PRS5B inhibitor complexes. 2020 The FEBS journal Result HIV M46I 126 130 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The side chain of residue 34 shows altered interactions with mutated residue N83D in the 80's loop in the core of the dimer. 2020 The FEBS journal Result HIV N83D 77 81 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The side chains of flap mutations M46I and I54V do not form van der Waals contacts with these inhibitors. 2020 The FEBS journal Result HIV I54V;M46I 43;34 47;38 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. The single substitution of I54V in PR has been described previously to alter flap conformation and effect inhibitor binding. 2020 The FEBS journal Result HIV I54V 27 31 PR 35 37 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. These interactions are disrupted in PRS5B due to the N83D mutation. 2020 The FEBS journal Result HIV N83D 53 57 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. This is consistent with Electronic Spin Resonance experiments on PR with D30N, M36I, and A71V mutations. 2020 The FEBS journal Result HIV A71V;D30N;M36I 89;73;79 93;77;83 PR 65 67 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Three other mutations in this cluster, Q61H, I63P, and I72V, project to the protein surface and do not appear to induce changes in the interior. 2020 The FEBS journal Result HIV I63P;I72V;Q61H 45;55;39 49;59;43 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Thus, the large distal movements for Loop 2 stemming from A71V and G73T mutations are compensated by repacking of the hydrophobic core from other mutations in the cluster. 2020 The FEBS journal Result HIV A71V;G73T 58;67 62;71 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Together, these substituted residues combine with other compensatory mutations to initiate a 1.2-3.0 A outward shift in all Calpha atoms of Loop 2 from mutated I64V through G73T. 2020 The FEBS journal Result HIV G73T;I64V 173;160 177;164 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. With the exception of subunit A of PRS5B/DRV, hinge residues 34 and 35 display alternate conformations for the main chain, while the side chains of Glu34 and E35N show alternate conformations or disorder. 2020 The FEBS journal Result HIV E35N 158 162 31920003 Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations. Within each hinge mutation cluster, E35N/D and M36I are shared, although each mutant contains different accessory mutations. 2020 The FEBS journal Result HIV E35D;E35N;M36I 36;36;47 42;42;51 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Another difference was that a very high proportion of M184V/I (NRTI mutation) occurred in ART-treated individuals in South China (66.0%), higher than that in North China (42.4%). 2020 EClinicalMedicine Result HIV M184I;M184V 54;54 61;61 NRTI 63 67 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Four mutations T69D (NRTI), K103N/S (NNRTI), M46I/L (PI) and L90M (PI) showed significantly different percentages in different subtypes (p < 0.05) (Table 1). 2020 EClinicalMedicine Result HIV K103N;K103S;L90M;M46I;M46L;T69D 28;28;61;45;45;15 35;35;65;51;51;19 NNRTI;NRTI;PI;PI 37;21;53;67 42;25;55;69 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Furthermore, a higher percentage of V106A/M (13.29%) in ART-treated individuals was observed in Central China than other regions. 2020 EClinicalMedicine Result HIV V106A;V106M 36;36 43;43 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Furthermore, very high percentages of M184I/V (26.3%) and K103N/S (39.5%) were found in subtype B strains in ART-naive individuals (Table 1), and some of them were scattered within the strains without the mutations, implying natural polymorphism of HIV-1 (Appendix 22). 2020 EClinicalMedicine Result HIV K103N;K103S;M184I;M184V 58;58;38;38 65;65;45;45 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Furthermore, we found a very high proportion (29.4%) of PI mutation M46I/L in ART-naive individuals, significantly higher than that in ART-treated individuals (1.3%). 2020 EClinicalMedicine Result HIV M46I;M46L 68;68 74;74 PI 56 58 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Furthermore, Y181C/I was predominant in B, CRF01_AE and other subtypes, whereas V106aA/M was predominant in CRF07_BC. 2020 EClinicalMedicine Result HIV Y181C;Y181I 13;13 20;20 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Importantly, a very high percentage of K103N/S (18.71%) was observed in ART-naive, but rarely seen in ART-treated individuals in Central China. 2020 EClinicalMedicine Result HIV K103N;K103S 39;39 46;46 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). In contrast, most M46I/L variants in other subtypes were scattered within the strains without this mutation, implying natural polymorphism of HIV-1. 2020 EClinicalMedicine Result HIV M46I;M46L 18;18 24;24 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). In NNRTI mutations, K103N/S and G190N/S were the two most common mutations in almost all subtypes (Table 2). 2020 EClinicalMedicine Result HIV G190N;G190S;K103N;K103S 32;32;20;20 39;39;27;27 NNRTI 3 8 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). In NRTI mutations, T215I/Y/S/N/F/E had the highest percentage (31.2%) in subtype B, whereas M184I/V had the most predominant percentage (43.8-73.3%) in CRF01_AE and other subtypes (Table 2 and Appendix 20). 2020 EClinicalMedicine Result HIV M184I;M184V;T215E;T215F;T215I;T215N;T215S;T215Y 92;92;19;19;19;19;19;19 99;99;34;34;34;34;34;34 NRTI 3 7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Low percentages of NRTI and NNRTI mutations, but a very high percentage (47.7%) of PI mutation (M46I/L) occurred in CRF01_AE; in contrast, high percentages of NRTI (M184I/V) and NNRTI (K103N/S and Y181C/I) mutations were observed in subtype B. 2020 EClinicalMedicine Result HIV K103N;K103S;M184I;M184V;M46I;M46L;Y181C;Y181I 185;185;165;165;96;96;197;197 193;193;172;172;102;102;204;204 NNRTI;NNRTI;NRTI;NRTI;PI 28;178;19;159;83 33;183;23;163;85 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The percentages of four mutations K65R (NRTI), M184I/V (NRTI), G190A/S (NNRTI) and M230L (NNRTI) were significantly correlated with subtypes (p < 0.05) (Table 2). 2020 EClinicalMedicine Result HIV G190A;G190S;K65R;M184I;M184V;M230L 63;63;34;47;47;83 70;70;38;54;54;88 NNRTI;NNRTI;NRTI;NRTI 72;90;40;56 77;95;44;60 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The phylogenetic tree showed that the majority of M46I/L-carrying CRF01_AE strains formed genetic clusters with a few dispersed within the strains without this mutation (Appendix 21), suggesting that most M46I/L-carrying CRF01_AE strains were more likely transmitted rather than generated by natural polymorphism. 2020 EClinicalMedicine Result HIV M46I;M46I;M46L;M46L 50;205;50;205 56;211;56;211 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The top NRTI mutations identified in ART-naive and ART-treated individuals were M184V/I (16.3% and 41.8%) and T215I/Y/S/D/F (20.9% and 9.5%), and the top NNRTI mutations were K103N/S (18.7% and 40.5%), Y181C/I (14.0% and 22.2%), and G190A/S (9.5% and 22.2%, respectively). 2020 EClinicalMedicine Result HIV G190A;G190S;K103N;K103S;M184I;M184V;T215D;T215F;T215I;T215S;T215Y;Y181C;Y181I 233;233;175;175;80;80;110;110;110;110;110;202;202 240;240;182;182;87;87;123;123;123;123;123;209;209 NNRTI;NRTI 154;8 159;12 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The two most commonly observed SDRMs M184V/I (NRTI) and M46I/L (PI) in North and South China were rarely found in Central China. 2020 EClinicalMedicine Result HIV M184I;M184V;M46I;M46L 37;37;56;56 44;44;62;62 NRTI;PI 46;64 50;66 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The vast majority of the M46I/L mutation occurred in CRF01_AE in ART-naive individuals (Table 1), suggesting that this mutation was likely a consequence of natural polymorphism of HIV-1. 2020 EClinicalMedicine Result HIV M46I;M46L 25;25 31;31 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. A total of 9588 PLHIV had at least one viral sequence containing the M184V/I mutation in the UK-HDRD in the time period considered. 2020 HIV medicine Result HIV M184I;M184V 69;69 76;76 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. At first detection of M184V/I, 559 (5.8%) PLHIV were recorded as ART-naive and 8311 (86.7%) as ART-experienced, with 718 (7.5%) without classification recorded. 2020 HIV medicine Result HIV M184I;M184V 22;22 29;29 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. For those people on 3TC/FTC, the M184V/I mutation remained in 59% of sequences obtained after >= 3 years of follow-up. 2020 HIV medicine Result HIV M184I;M184V 33;33 40;40 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. However, for those not on 3TC/FTC, the proportion of sequences with the M184V/I mutation dropped from 18% 6 months to 1 year after ART regimen switch to 11% after >= 3 years (Table S1). 2020 HIV medicine Result HIV M184I;M184V 72;72 79;79 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Linkage to any clinical data (in UK CHIC) was possible in 5068 PLHIV, with information on new ART regimen within 1 year of first detection of the M184V/I mutation in 3535 (excluding 32 people for whom the exact ART regimen was masked because of enrolment in a randomized trial). 2020 HIV medicine Result HIV M184I;M184V 146;146 153;153 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Of the 3535 individuals in whom there was a change to the ART regimen (or ART initiation) within 1 year of detection of M184V/I: in 234 there was viral suppression prior to ART change, in 159 people the last recorded VL was prior to ART change and in 284 no VL measurements were recorded prior to another subsequent alteration of ART, resulting in 2858 people in whom virological response to ART switch could be evaluated. 2020 HIV medicine Result HIV M184I;M184V 120;120 127;127 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The differences observed were not altered by also considering interactions with other drugs for which the M184V/I mutation reduces (abacavir and didanosine) or increases (stavudine and zidovudine) susceptibility. 2020 HIV medicine Result HIV M184I;M184V 106;106 113;113 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The prevalence of M184V/I in resistance tests of ART-experienced PLHIV decreased substantially over the period 2002-2010, stabilizing at 10-15% beyond this. 2020 HIV medicine Result HIV M184I;M184V 18;18 25;25 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Viral suppression after detection of M184V/I. 2020 HIV medicine Result HIV M184I;M184V 37;37 44;44 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 1B), the RGDA/Q112D virus showed increased CPSF6-358 resistance, whereas the RGDA/Q112D+Q4R virus exhibited CPSF6-358 resistance comparable to that obtained with the RGDA and WT viruses (6.0% vs. 2020 AIDS research and human retroviruses Result HIV Q112D;Q112D;Q4R 14;82;88 19;87;91 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 3.6%, respectively), the combination of these substitutions (Q4R/Q112E) diminished CPSF6-358 resistance to levels comparable to that of the WT virus (4.6% vs. 2020 AIDS research and human retroviruses Result HIV Q112E;Q4R 65;61 70;64 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 3A, B), the RGDA/Q4R virus exhibited increased CPSF6-358 resistance compared with that of the RGDA virus (67.8% vs. 2020 AIDS research and human retroviruses Result HIV Q4R 17 20 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 4C), phenocopying the effect of the Q112D substitution. 2020 AIDS research and human retroviruses Result HIV Q112D 36 41 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 5.7%, respectively), suggesting that the Q4R substitution restored the CA-CPSF6 interaction caused by the Q112D substitution, although the Q4R substitution alone also greatly diminished the CA-CPSF6 interaction of the WT virus. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R;Q4R 106;41;139 111;44;142 Capsid;Capsid 71;190 73;192 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 8.0%, respectively), demonstrating that the Q4R substitution restored the CA-CPSF6 interaction of the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 107;44 112;47 Capsid 74 76 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Although the RGDA (H87R, A88G, P90D, and P93A) substitutions did not alter the CPSF6-358 resistance compared with that of the WT virus (6.0% vs. 2020 AIDS research and human retroviruses Result HIV A88G;H87R;P90D;P93A 25;19;31;41 29;23;35;45 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. As a result, it seemed likely that the salt bridge restores the decreased CA-CPSF6 interaction of RGDA/Q112D. 2020 AIDS research and human retroviruses Result HIV Q112D 103 108 Capsid 74 76 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Combination of the Q4R and Q112E substitutions confers normal levels of CA-CPSF6 interaction to the SIVcpzMT145 virus. 2020 AIDS research and human retroviruses Result HIV Q112E;Q4R 27;19 32;22 Capsid 72 74 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Consistent with our recent findings, the RGDA/Q112D virus showed higher CPSF6-358 resistance than did the WT virus. 2020 AIDS research and human retroviruses Result HIV Q112D 46 51 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Conversely, the Q4R/Q112D virus had CPSF6-358 resistance comparable to that of the WT virus (8.1% vs. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 20;16 25;19 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. D), an effect that was distinct from that obtained with the RGDA/Q112D+Q4R virus. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 65;71 70;74 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. However, it was unclear whether the effect of the Q4R substitution on interaction with CPSF6 was specifically associated with the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 135;50 140;53 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In addition, electrostatic surface potential prediction indicated that the CAs of WT and RGDA/Q112D+Q4R viruses possess relatively neutral surfaces, whereas those of the NL4-3 Q4R virus or the RGDA/Q112D virus were likely more positively or negatively charged, respectively. 2020 AIDS research and human retroviruses Result HIV Q112D;Q112D;Q4R 198;94;100 203;99;103 Capsid 75 78 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In contrast, in the CAs of the NL4-3 Q4R or RGDA/Q112D viruses, the salt bridge interaction between the 4th and 112th residues was not predicted. 2020 AIDS research and human retroviruses Result HIV Q112D 49 54 Capsid 20 23 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In contrast, the virus encoding the R4Q/E112Q double mutant CA showed CPSF6-358 resistance comparable to that of the WT virus (4.1% vs. 2020 AIDS research and human retroviruses Result HIV E112Q;R4Q 40;36 45;39 Capsid 60 62 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In this study, we hypothesized that the combination of Q4R and Q112E substitutions was fixed in the SIVcpzMT145 strain to maintain the CA-CPSF6 interaction. 2020 AIDS research and human retroviruses Result HIV Q112E;Q4R 63;55 68;58 Capsid 135 137 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Interestingly, the SIVcpzMT145 strain possesses the Q112E substitution, which is a very rare amino acid substitution in HIV-1-lineage viruses. 2020 AIDS research and human retroviruses Result HIV Q112E 52 57 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Notably, one strain of SIVcpz (SIVcpzMT145) encodes CA with the Q4R substitution, as indicated in the HIV mutation database . 2020 AIDS research and human retroviruses Result HIV Q4R 64 67 Capsid 52 54 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Notably, the CPSF6-358 resistance of the RGDA/Q112D+Q4R virus was comparable to that of the WT virus (6.0% vs. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 46;52 51;55 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. On the other hand, the N74D virus, a CPSF6 binding-deficient CA mutant, was not affected by CPSF6-358. 2020 AIDS research and human retroviruses Result HIV N74D 23 27 Capsid 61 63 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Opposite effects of the Q4R substitution on CA-CPSF6 interactions of the WT and RGDA/Q112D viruses. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 85;24 90;27 Capsid 44 46 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Presumably the Q112E substitution counteracts the increased CPSF6-358 resistance associated with the Q4R substitution. 2020 AIDS research and human retroviruses Result HIV Q112E;Q4R 15;101 20;104 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Results showed that either the Q4R substitution or the Q112D substitution yielded increased CPSF6-358 resistance compared with that of the WT virus (62.6% or 20.7% vs. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 55;31 60;34 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. The models suggested that the CA molecules of the RGDA/Q112D+Q4R virus generated an intermonomer salt bridge interaction between the R4 and D112 residues. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 55;61 60;64 Capsid 30 32 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. The results revealed that viruses encoding CAs with either the R4Q substitution or the E112Q substitution exhibited increased CPSF6-358 resistance compared with that of WT SIVcpzMT145 virus strain (14.3% or 6.9% vs. 2020 AIDS research and human retroviruses Result HIV E112Q;R4Q 87;63 92;66 Capsid 43 46 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. These observations suggested that the charged CA surface of the RGDA/Q112D virus is neutralized by the salt bridge formed by a Q4R substitution. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 69;127 74;130 Capsid 46 48 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. These results suggested that while the RGDA substitutions minimally affected the CA-CPSF6 interaction, either the Q4R substitution or the Q112D substitution significantly diminish CA-CPSF6 interaction by the RGDA virus. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 138;114 143;117 Capsid;Capsid 81;180 83;182 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. This result suggested that the Q4R substitution decreased the CA-CPSF6 interaction of the WT virus, yielding an effect opposite to that obtained with the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Result HIV Q112D;Q4R 159;31 164;34 Capsid 62 64 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. To address this question, we first examined the impact of the Q4R substitution on the CA-CPSF6 interaction of NL4-3 (WT) virus. 2020 AIDS research and human retroviruses Result HIV Q4R 62 65 Capsid 86 88 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. To directly examine the impact of the 4th and 112th residues of CA on the CA-CPSF6 interaction, we compared the CPSF6-358 resistances of the RGDA, RGDA/Q4R, RGDA/Q112D, and RGDA/Q112D+Q4R viruses. 2020 AIDS research and human retroviruses Result HIV Q112D;Q112D;Q4R;Q4R 162;178;152;184 167;183;155;187 Capsid;Capsid 64;74 66;76 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. To examine the relevance of the Q112E substitution to the Q4R substitution, we introduced genetic mutations encoding the Q112E and Q4R/Q112E substitutions into NL4-3 CA and tested the CPSF6-358 resistance of these viruses. 2020 AIDS research and human retroviruses Result HIV Q112E;Q112E;Q112E;Q4R;Q4R 32;121;135;58;131 37;126;140;61;134 Capsid 166 168 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. To test possible reasons for the discrepant effect of the Q4R substitution between RGDA/Q112D and WT viruses, we constructed structural models of the CA proteins encoded by the RGDA/Q112D, RGDA/Q112D+Q4R, and Q4R viruses. 2020 AIDS research and human retroviruses Result HIV Q112D;Q112D;Q112D;Q4R;Q4R;Q4R 88;182;194;58;200;209 93;187;199;61;203;212 Capsid 150 152 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We further examined the CPSF6-358 resistance of the NL4-3 Q4R, Q112D, and Q4R/Q112D viruses (in the absence of the RGDA mutations). 2020 AIDS research and human retroviruses Result HIV Q112D;Q112D;Q4R 63;78;74 68;83;77 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We generated mutants of the SIVcpzMT145 strain encoding CA harboring the R4Q, E112Q, or R4Q/E112Q substitutions. 2020 AIDS research and human retroviruses Result HIV E112Q;E112Q;R4Q;R4Q 78;92;73;88 83;97;76;91 Capsid 56 58 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We recently showed that the Q4R substitution restored the CA-CPSF6 interaction of the RGDA/Q112D (H87R, A88G, P90D, P93A, and Q112D) virus. 2020 AIDS research and human retroviruses Result HIV A88G;H87R;P90D;P93A;Q112D;Q112D;Q4R 104;98;110;116;126;91;28 108;102;114;120;131;96;31 Capsid 58 60 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We showed that the RGDA/Q112D+Q4R virus exhibited lower CPSF6-358 resistance than did the RGDA/Q112D virus. 2020 AIDS research and human retroviruses Result HIV Q112D;Q112D;Q4R 95;24;30 100;29;33 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. While viruses encoding CA with either the Q4E substitution or the Q112E substitution showed increased CPSF6-358 resistance compared with that of the WT virus (32.7% or 9.1% vs. 2020 AIDS research and human retroviruses Result HIV Q112E;Q4E 66;42 71;45 Capsid 23 25 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Aptamers 148.1-38m and 70.05core2 were both able to inhibit all eight mutants, at least to some degree; however, mutants P420A, L422A and K424A were noticeably less susceptible than the other RTs to inhibition by aptamer 148.1-38m (NFEP > 0.7, Figure 4A), while all eight mutants remained susceptible to 70.05core2 inhibition (NFEP 0.15 to 0.45). 2020 Nucleic acids research Result HIV K424A;L422A;P420A 138;128;121 143;133;126 RT 192 195 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. In contrast, RT mutant R277K was not susceptible to inhibition by aptamer 70.05core2 at any tested concentration (up to 180 nM), while all other RTs were equivalently inhibited in a concentration-dependent manner by this aptamer (Figure 5B), again highlighting differences in amino acid sequence sensitivities for aptamers from different structural families. 2020 Nucleic acids research Result HIV R277K 23 28 RT;RT 13;145 15;148 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Inhibition of P420A was partially rescued at high concentration of aptamer. 2020 Nucleic acids research Result HIV P420A 14 19 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Mutant T419A was also included as a internal control and its polymerase activity was similar to that of WT RT. 2020 Nucleic acids research Result HIV T419A 7 12 Pol;RT 61;107 71;109 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Nevertheless, none of these alanine substitutions yielded the degree of resistance obtained with an R277K mutant RT, which extended essentially all of the input p/t to full-length product in the presence of 70.05core2, even while remaining susceptible to inhibition by 148.1-38m (Figure 4A). 2020 Nucleic acids research Result HIV R277K 100 105 RT 113 115 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. P420A, L422A and K424A mutants are less susceptible to 148.1-38m inhibition. 2020 Nucleic acids research Result HIV K424A;L422A;P420A 17;7;0 22;12;5 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Polymerase activities of the three mutants (P420A, L422A and K424A) were similar to, or slightly less than, that of WT RT (Figure 4B and Supplementary Figure S12), ruling out the possibility that their reduced sensitivities to inhibition by 148.1-38m could be due to enhanced abilities to bind or extend the DNA substrate. 2020 Nucleic acids research Result HIV K424A;L422A;P420A 61;51;44 66;56;49 Pol;RT 0;119 10;121 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Protection at peptides covering position 277 was observed in both complexes but were notably were higher in RT-70.05core2 than in RT-148.1 complex (Supplementary Figure S9), consistent with the finding that R277K mutation abolished the inhibitory function of F1Pk aptamers but not UCAA aptamers. 2020 Nucleic acids research Result HIV R277K 207 212 RT;RT 108;130 110;132 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Since full-length aptamer 70.05 had been previously demonstrated to be unable to bind R277K, the strong resistance phenotype of R277K mutant against 70.05core2 was expected. 2020 Nucleic acids research Result HIV R277K;R277K 86;128 91;133 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. The difference in inhibition by aptamers 148.1-38m and 70.05core2 is especially evident for RT mutants L422A and K424A (P = 0.0016 and 0.0004, respectively) and for N418A (P = 0.02), even though both aptamers inhibit N418A with NFEP < 0.6. 2020 Nucleic acids research Result HIV K424A;L422A;N418A;N418A 113;103;165;217 118;108;170;222 RT 92 94 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. The remaining positions (418, 421, 423 and 424) were conserved within group M (HXB2, NL4-3, 93TH and 94CY) and SIVcpz (SIV-US) (Supplementary Figure S10A). 2020 Nucleic acids research Result HIV S10A 149 153 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. The singly substituted p51 subunits were co-expressed with wild-type p66 and purified to yield eight enzymatically active mutant RTs (N418A, T419A, P420A, P421A, L422A, V423A, K424A and L425A) (Supplementary Figure S11). 2020 Nucleic acids research Result HIV K424A;L422A;L425A;N418A;P420A;P421A;T419A;V423A 176;162;186;134;148;155;141;169 181;167;191;139;153;160;146;174 RT 129 132 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. This weak resistance is consistent with the slight decrease in binding affinity of 148-38m for P420A compared to WT HXB2 (Supplementary Figure S13). 2020 Nucleic acids research Result HIV P420A 95 100 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. When both aptamers were titrated against four RTs (WT HXB2, T419A, P420A and R277K), aptamer 148.1-38mer inhibited P420A weakly compared to its inhibition of HXB2, T419A and R277K (Figure 5A). 2020 Nucleic acids research Result HIV P420A;P420A;R277K;R277K;T419A;T419A 67;115;77;174;60;164 72;120;82;179;65;169 RT 46 49 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. 35,428 copies/mL, p = 0 0032), including those with single Y181C, M184V or G190A mutations, and those with multiple NNRTI/NRTI mutations, but not among those with single K103N mutations (Table 3). 2020 EClinicalMedicine Result HIV G190A;K103N;M184V;Y181C 75;170;66;59 80;175;71;64 NNRTI;NRTI 116;122 121;126 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Among participants taking NVP-ART, those with a single K103N or multiple NNRTI/NRTI mutations had higher rates of virologic failure compared to those with no PDR mutations (Table 2). 2020 EClinicalMedicine Result HIV K103N 55 60 NNRTI;NRTI 73;79 78;83 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Among the 59 participants with PDR, NNRTI mutations (K103N, Y181C, G190A) were detected in all but one (98 3%) and NRTI mutations (K65R, M184V) were detected in 14 (23 7%). 2020 EClinicalMedicine Result HIV G190A;K103N;K65R;M184V;Y181C 67;53;131;137;60 72;58;135;142;65 NNRTI;NRTI 36;115 41;119 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. In addition, the OLA did not detect resistance to NNRTI in one participant with V106M and Y188C, or resistance to 3TC in four participants with M184I, as these mutations were not interrogated by the OLA. 2020 EClinicalMedicine Result HIV M184I;V106M;Y188C 144;80;90 149;85;95 NNRTI 50 55 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. In contrast, among participants taking EFV-ART only those with multiple mutations had increased rates of virologic failure compared to those with wild-type genotype, and those with only K103N had rates of virologic failure similar to those with wild-type HIV (Table 2). 2020 EClinicalMedicine Result HIV K103N 186 191 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Single NNRTI mutations were detected in 37 (62 7%), with K103N most frequently detected (30/59, 50 8%), multiple NNRTI mutations were detected in 8 (13 6%), and multiple NNRTI/NRTI mutations in 13 (22 0%). 2020 EClinicalMedicine Result HIV K103N 57 62 NNRTI;NNRTI;NNRTI;NRTI 7;113;170;176 12;118;175;180 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Among these, K103N, Y181C or Y188L, carried by RT, are the most prevalent mutants. 2020 European journal of medicinal chemistry Result HIV K103N;Y181C;Y188L 13;20;29 18;25;34 RT 47 49 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. As the L100I/K103N double-mutated RT resisted EFV, the docking. 2020 European journal of medicinal chemistry Result HIV K103N;L100I 13;7 18;12 RT 34 36 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. As the mutations of Y181C or Y188L occur, the forces between NNRTIs and RT by pi-pi interaction disappear. 2020 European journal of medicinal chemistry Result HIV Y181C;Y188L 20;29 25;34 NNRTI;PI;PI;RT 61;78;81;72 67;80;83;74 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Compound 10i docking into the K103N/Y181C double-mutated RT (5VQY). 2020 European journal of medicinal chemistry Result HIV K103N;Y181C 30;36 35;41 RT 57 59 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. For the positive control NVP, which is resisted by K103N/Y181C double-mutated RT, the docking simulation. 2020 European journal of medicinal chemistry Result HIV K103N;Y181C 51;57 56;62 RT 78 80 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. In order to better understand the possible binding mode of the active compounds, the potent 10i and CI - 39 as well as the positive controls NVP and EFV were docked into the HIV-1 WT RT (PDB code: 1TL1) and the HIV-1 RT mutants RT-Y181C (PDB code: 1JLB), RT-K103N/Y181C (PDB code: 5VQY), and RT-L100I/K103N (PDB code: 2ZE2), respectively. 2020 European journal of medicinal chemistry Result HIV K103N;K103N;L100I;Y181C;Y181C 258;301;295;231;264 263;306;300;236;269 RT;RT;RT;RT;RT 183;217;228;255;292 185;219;230;257;294 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. In the case of the L100I/K103N double-mutated RT (Figure 6c), the docking exhibited a position exchange between the indole and pyridine ring moieties in the interacting model, and the hydroxy group from isomerization of the acetamide unit in 10i was hydrogen-bonded to the terminal carbamide oxygen of the mutated Asn103. 2020 European journal of medicinal chemistry Result HIV K103N;L100I 25;19 30;24 RT 46 48 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Particularly, 10i (EC50 = 0.43 muM) was more notably more active against the double mutant L100I/K103N comparing to both NVP (EC50 = 0.76 muM) and EFV (EC50 = 1.08 muM). 2020 European journal of medicinal chemistry Result HIV K103N;L100I 97;91 102;96 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. The docking into the Y181C mutated RT (1JLB). 2020 European journal of medicinal chemistry Result HIV Y181C 21 26 RT 35 37 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. When Lys103 changes to asparagine, the RT catalytic pocket is preferred in its closed form, resulting in less electrostatic forces within the NNRTIs. 2020 European journal of medicinal chemistry Result HIV K103N 5 33 NNRTI;RT 142;39 148;41 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. As expected, L210W (75%, p = 0.03) and T215 mutations (70%, p = 0.0005) were significantly noted more in AZT/3TC/EFV as compared to TDF/3TC/EFV group. 2020 AIDS research and therapy Result HIV L210W 13 18 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. Comparisons of individual mutations within the NNRTI class showed the most frequent mutation to be K103N; this occurred in 98 (53.8%) of the patients. 2020 AIDS research and therapy Result HIV K103N 99 104 NNRTI 47 52 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. However, comparisons for individual mutations within the NRTI class of drugs indicated that mutations K65R, L74I, Y115F, L210W and T215 mutations differed significantly among the two regimens. 2020 AIDS research and therapy Result HIV K65R;L210W;L74I;Y115F 102;121;108;114 106;126;112;119 NRTI 57 61 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. However, when we compared individual mutations we found that M184V/I (p = 0.015), Y188L (p = 0.008) and TAMs (p = 0.011) were significantly more common in Subtype A as compared to Subtype D and others. 2020 AIDS research and therapy Result HIV M184I;M184V;Y188L 61;61;82 68;68;87 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. K65R (95.2%, p = 0.00005), Y115F (85%, p = 0.005) and L74I (82.6%, p= 0.005) mutations appeared more in the TDF/3TC/EFV group as compared to AZT/3TC/EFV group. 2020 AIDS research and therapy Result HIV L74I;Y115F;K65R 54;27;0 58;32;4 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. On the other hand, the least frequent NRTI mutations were F77L that occurred in 2 (1.1%) of the patients followed by Q151M and T69D at 3 (1.6%). 2020 AIDS research and therapy Result HIV F77L;Q151M;T69D 58;117;127 62;122;131 NRTI 38 42 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. This was followed by G190A/S/E/G that occurred in 55 (30.2%) of the patients, P236L mutation occurred in 2 (1.1%) and L234I that occurred in only 4 (2.2%) of the participants. 2020 AIDS research and therapy Result HIV G190A;G190E;G190G;G190S;L234I;P236L 21;21;21;21;118;78 32;32;32;32;123;83 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. This was followed by K70R, K65R and K219 mutations occurring at 56 (24.3%), 42 (23.1%) and 40 (22%) respectively. 2020 AIDS research and therapy Result HIV K65R;K70R 27;21 31;25 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. When we compared individual mutations within the NRTI class, M184V/I mutation had the highest prevalence of 120 (65.9%) among patients. 2020 AIDS research and therapy Result HIV M184I;M184V 61;61 68;68 NRTI 49 53 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. Within the NNRTI class, G190 mutations (69.1%, p = 0.015), Y181C (78.6%, p = 0.008), L100I (82.4%, p = 0.019) were significantly more in the TDF/3TC/EFV group whereas mutation K238T (71.4%, p = 0.035) was significantly more in the AZT/3TC/EFV group. 2020 AIDS research and therapy Result HIV K238T;L100I;Y181C 176;85;59 181;90;64 NNRTI 11 16 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Among all the mutants tested, the N279A and N280D mutations in 25710 rendered the viruses more sensitive to neutralization by plasma from all time points in both G1015R and G1020R macaques (Figure 1 and Figure 2). 2020 Viruses Result HIV G1015R;G1020R;N279A;N280D 162;173;34;44 168;179;39;49 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Among three loop D mutants tested, the N276D mutant were more sensitive to three CD4bs bnAbs (VRC01, VRC03 and N6). 2020 Viruses Result HIV N276D 39 44 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Both N279A and N280D mutations in 25710 also made the viruses more sensitive to neutralization in macaques infected with SHIVSF162P3 or SHIVCHN19P4 (Figure 6), in which only low titer neutralization activities with limited breadth were detected after long-term infection. 2020 Viruses Result HIV N279A;N280D 5;15 10;20 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Both W459'R and W459'C mutants were much more resistant to week 217 plasma than the wt SHIV1157, while the N460D mutant was similarly sensitive to neutralization as wt SHIV1157 (Figure 5A), which could explain the reason this mutation disappeared from those sequences of week 350. 2020 Viruses Result HIV N460D 107 112 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Broadly neutralizing activities were detected in two Chinese rhesus macaques (G1015R and G1020R) infected with SHIV1157 after 6 years of natural infection in our previous study. 2020 Viruses Result HIV G1015R;G1020R 78;89 85;95 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Compared to wt CAP45, the neutralization titers against the N160A mutant were reduced by 75% and 70% by week 217 and 350, respectively (Figure 3A), but the neutralization titer of the N160K mutant of 25710 was only slightly lower compared to wt 25710 (Figure 2). 2020 Viruses Result HIV N160A;N160K 60;184 65;189 Capsid 15 17 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. However, both D279A and N280D mutants were more sensitive to week 350 plasma from G1015R. 2020 Viruses Result HIV D279A;G1015R;N280D 14;82;24 19;88;29 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. However, none of them were similar to those mutations (N160A, T162A, K169V/E) that were found to be resistant to known V2 bnAbs. 2020 Viruses Result HIV K169E;K169V;N160A;T162A 69;69;55;62 76;76;60;67 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. However, the N279A was more resistant to VRC01 than wt 25710, similarly sensitive to VRC03, but more sensitive to N6 (Figure 7). 2020 Viruses Result HIV N279A 13 18 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. However, the neutralization titers of the week 350 plasma were reduced by 62% and 55% for the N625A (gp120-gp41 interface) and N276D mutants, respectively. 2020 Viruses Result HIV N276D;N625A 127;94 132;99 gp120;gp41 101;107 106;111 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. It did not neutralize the gp120-gp41 interface mutant N611A (Figure 3B). 2020 Viruses Result HIV N611A 54 59 gp120;gp41 26;32 31;36 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. N279A and N280D Mutations Render Env Mutants More Sensitive to Neutralization. 2020 Viruses Result HIV N280D;N279A 10;0 15;5 Env 33 36 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. No mutations at position 280 were detected in any sequences while one reversion mutation D279N was found in only 1 out of 23 sequences at week 214. 2020 Viruses Result HIV D279N 89 94 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. No samples from G1020R were available for similar analysis. 2020 Viruses Result HIV G1020R 16 22 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Only two mutation sites (N160K/A and N276D) were shared between CAP45 and 25710, but neutralization sensitivities of both mutants were different between these two viruses. 2020 Viruses Result HIV N160A;N160K;N276D 25;25;37 33;33;42 Capsid 64 66 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Only weakly reduced neutralization titers (by 65% to 75%) for the N160A, T162A, K169V and K169E mutants were detected. 2020 Viruses Result HIV K169E;K169V;N160A;T162A 90;80;66;73 95;85;71;78 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Our previous study showed that 25710 were neutralized by plasma from both G1015R and G1020R from week 27 post infection. 2020 Viruses Result HIV G1015R;G1020R 74;85 80;91 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Plasma samples from only four time points (weeks 54, 217, 293 and 350) in G1020R were still available for the mapping analysis (Figure 1). 2020 Viruses Result HIV G1020R 74 80 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Since all but the plasma sample from week 350 in G1015R had been exhausted, only the week 350 plasma was analyzed. 2020 Viruses Result HIV G1015R 49 55 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Since viruses with CD4bs mutations (N276D and N279A), V2 mutations (N160A, T162A, K169V and K169E) and gp120-gp41 interface mutations (N611A and N625A) were found resistant to neutralization by week 350 plasma in G1015R, these regions were carefully examined. 2020 Viruses Result HIV G1015R;K169E;K169V;N160A;N276D;N279A;N611A;N625A;T162A 213;92;82;68;36;46;135;145;75 219;97;87;73;42;51;141;150;80 gp120;gp41 103;109 108;113 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The I192T mutant was similarly neutralized as wt SHIV1157. 2020 Viruses Result HIV I192T 4 9 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The N276D mutant was slightly more resistant to week 350 plasma than wt SHIV1157 (Figure 5C). 2020 Viruses Result HIV N276D 4 9 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The N276D mutation in loop D was detected in 7 out of 23 sequences at week 214 but became undetectable at week 350 (Figure 4A). 2020 Viruses Result HIV N276D 4 9 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The N276D, N279A and N280D mutations in loop D generally have low binding affinity and are more resistant to CD4bs bnAbs, but the differences in binding and neutralizing capabilities vary significantly. 2020 Viruses Result HIV N276D;N279A;N280D 4;11;21 9;16;26 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The N280D mutant were more resistant to both VRC01 and VRC03 but more sensitive to N6. 2020 Viruses Result HIV N280D 4 9 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The N280D mutation also rendered the Ce0217 and X1632 viruses more sensitive to the week 350 plasma in G1015R, while the N279A mutant of Ce0217 was more resistant (Figure 3B,C). 2020 Viruses Result HIV G1015R;N279A;N280D 103;121;4 109;126;9 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The N460D mutation were found in 4 of 23 (17%) sequences of the week 214 sequences. 2020 Viruses Result HIV N460D 4 9 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The neutralization against wt 25710 was also detected first at week 27 and its neutralization titers gradually increased over time as in G1020R (Figure 2). 2020 Viruses Result HIV G1020R 137 143 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The neutralization profile in G1015R was similar to that detected in G1020R (Figure 2). 2020 Viruses Result HIV G1015R;G1020R 30;69 36;75 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. The reversion mutation D279N in X1632 had no effect on the neutralization susceptibility (Figure 3C). 2020 Viruses Result HIV D279N 23 28 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. These results showed that the gp120-gp41 interface was most likely targeted by nAbs in the week 350 plasma from G1015R. 2020 Viruses Result HIV G1015R 112 118 gp120;gp41 30;36 35;40 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. These results showed that the N279A and N280D mutations had different impacts on resistance to neutralization by various CD4bs bnAbs, but were more sensitive to neutralization by bnAbs targeting V1V2 or V3. 2020 Viruses Result HIV N279A;N280D 30;40 35;45 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. These results suggested that nAbs with V2, CD4bs or V3 specificities were elicited in G1020R while nAbs targeting CD4bs and gp120-gp41 interface were elicited in G1015R. 2020 Viruses Result HIV G1015R;G1020R 162;86 168;92 gp120;gp41 124;130 129;134 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. This demonstrated that both W459'R and W459'C mutations were selected by nAbs targeting V5 in G1015R. 2020 Viruses Result HIV G1015R 94 100 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. This suggests that the D279A or N280D mutation would be more sensitively neutralized by the autologous plasma than the wt SHIV1157 in G1015R, although either D279A or N280D mutation was not detected in G1015R. 2020 Viruses Result HIV D279A;D279A;G1015R;G1015R;N280D;N280D 23;158;134;202;32;167 28;163;140;208;37;172 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. This was consistent with the mapping results with the 25710 mutants (Figure 2), suggesting that the transient presence of the N276D mutation at week 214 was indeed selected by nAbs targeting loop D in G1015R (Figure 4A). 2020 Viruses Result HIV G1015R;N276D 201;126 207;131 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Thus, we used a set of eight 25710 env mutants that were known for resistant to neutralization by bnAbs targeting V2, CD4bs, V3 and gp120-gp41 interface to determine when bnAb-like neutralization specificities developed in the plasma of G1015R and G1020R. 2020 Viruses Result HIV G1015R;G1020R 237;248 243;254 gp120;gp41;Env 132;138;35 137;142;38 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. To determine if these mutation sites were indeed targeted by autologous nAbs in G1015R, we examined the env gene sequences from three time points (weeks 27, 214 and 350), for which there were still enough plasma samples for single genome amplification (SGA) analysis. 2020 Viruses Result HIV G1015R 80 86 Env 104 107 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. When four V2 mutants were tested, the K171R mutant was much more resistant to neutralization than wt SHIV1157, but both I165L and V172A mutants were only slightly more resistant (Figure 5C). 2020 Viruses Result HIV I165L;K171R;V172A 120;38;130 125;43;135 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. When tested with a set of 11 env mutants of CAP45, nAbs targeting V2 were identified in the week 321 plasma from G1015R. 2020 Viruses Result HIV G1015R 113 119 Env;Capsid 29;44 32;46 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. When tested with the Ce0217 mutant set, the neutralization titer was reduced by 57% for the CD4bs mutant N279A. 2020 Viruses Result HIV N279A 105 110 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. When tested with the X1632 mutant set, the plasma only showed weakly reduced neutralization activity (by 51%) against the N611A mutant. 2020 Viruses Result HIV N611A 122 127 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. When V1V2 bnAb PG9 and V3 bnAb 10-1074 were tested, the N276D mutant was similarly neutralized as wt 25710, but both N279A and N280D mutants were more sensitive to neutralization. 2020 Viruses Result HIV N276D;N279A;N280D 56;117;127 61;122;132 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. While the N276D mutant was more resistant to neutralization than wt 25710, it was only slightly more resistant than wt CAP45. 2020 Viruses Result HIV N276D 10 15 Capsid 119 121 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. While the neutralization titers against wt 25710 continuously increased from week 54 to week 350 (Figure 1), the neutralization titers of the plasma were reduced by more than half for the N160K (V2), N276D (CD4bs) and N332A (V3) mutants only by week 350 (Figure 1D). 2020 Viruses Result HIV N160K;N276D;N332A 188;200;218 193;205;223 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. While the neutralization titers against wt 25710 in both macaques continuously increased over time, the neutralization titers against both N279A and N280D mutants remained at the similar levels. 2020 Viruses Result HIV N279A;N280D 139;149 144;154 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. While the week 350 plasma could potently neutralize wt 25710 at 1:286 dilution, its neutralization titers were reduced by 91% and 72% for the N332A and N160K mutants, respectively, and it did not neutralize the N276D mutant. 2020 Viruses Result HIV N160K;N276D;N332A 152;211;142 157;216;147 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Wild type (wt) 25710 could be neutralized by autologous plasma as early as at week 27 in G1020R. 2020 Viruses Result HIV G1020R 89 95 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Also, we found the L101I/T124A combination in 7/25 samples (28%) (subjects 3, 5, 11, 17, 19, 23 and 25). 2020 AIDS research and therapy Result HIV L101I;T124A 19;25 24;30 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. However, one sample (subject 13) had the presence of the E157Q substitution (Table 2). 2020 AIDS research and therapy Result HIV E157Q 57 62 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. The DTG resistance associated mutation R263K was not found. 2020 AIDS research and therapy Result HIV R263K 39 44 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. Among the 7 cases with NRTI mutations, the most common was M184I/V, which is known to confer high-level resistance to both emtricitabine (FTC) and 3TC. 2020 PloS one Result HIV M184I;M184V 59;59 66;66 NRTI 23 27 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. Other NRTI resistance mutations were K65R and K219R. 2020 PloS one Result HIV K219R;K65R 46;37 51;41 NRTI 6 10 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. The K103N mutation was the most common, followed by E138A/G, G190A and A98G, and then V179D/E/T and Y181C (Table 2). 2020 PloS one Result HIV A98G;E138A;E138G;G190A;K103N;V179D;V179E;V179T;Y181C 71;52;52;61;4;86;86;86;100 75;59;59;66;9;95;95;95;105 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. The K103N, Y181C, and G190A are known to confer high-level resistance to NVP, and intermediate to high resistance to EFV. 2020 PloS one Result HIV G190A;K103N;Y181C 22;4;11 27;9;16 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. The two non-polymorphic accessory mutations associated with PI mutations were L33F and I54V, and were observed in three PI resistant patients. 2020 PloS one Result HIV I54V;L33F 87;78 91;82 PI;PI 60;120 62;122 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Among RTI-treated patients, the prevalence of the S68G mutation increased significantly in almost all subtypes (p < 0.05), except subtype F that exhibited a slight decrease. 2020 BMC infectious diseases Result HIV S68G 50 54 RT 6 9 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Among the three patients infected with CRF01_AE not carrying the natural polymorphism S68G prior to ART, The K65R mutation was detected in patient-302335 as the dominant mutant quasispecies 3 months post-ART, accounting for 92.99%, which remained at a high level (94.63%) when tested 6-months post-ART; at that time, the S68G mutation was detected among 51.14% quasispecies. 2020 BMC infectious diseases Result HIV K65R;S68G;S68G 109;86;321 113;90;325 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. At the end of culture, the K65R/S68G double mutation strains outgrew those of the K65R mutation irrespective of the input ratio. 2020 BMC infectious diseases Result HIV K65R;K65R;S68G 27;82;32 31;86;36 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. CRF01_AE viruses demonstrated a 9.7% increase in S68G mutation between RTI-treated and RTI-naive individuals, the greatest increase observed among all subtypes (Additional file 2: Table S1). 2020 BMC infectious diseases Result HIV S68G 49 53 RT;RT 71;87 74;90 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Frequency of the S68G mutation increased significantly in RTI-treated patients and commonly co-occurred with the K65R mutation among CRF01_AE strains. 2020 BMC infectious diseases Result HIV K65R;S68G 113;17 117;21 RT 58 61 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. However, the K65R mutation was not detected until 7 months post ART, when only 11.28% of the quasispecies were found to have the K65R mutation. 2020 BMC infectious diseases Result HIV K65R;K65R 13;129 17;133 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In further follow-up time points (at 7-12 months post ART), almost all quasispecies carried the K65R/S68G double mutation in these two patients. 2020 BMC infectious diseases Result HIV K65R;S68G 96;101 100;105 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In the 1:1 input group, the composition of K65R/S68G mutants increased from 50 to 84%. 2020 BMC infectious diseases Result HIV K65R;S68G 43;48 47;52 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In the 4:6 input group, the composition of K65R/S68G mutants increased from 60 to 88%. 2020 BMC infectious diseases Result HIV K65R;S68G 43;48 47;52 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In the 9:1 input group, the composition of K65R/S68G mutants increased from 10 to 62%. 2020 BMC infectious diseases Result HIV K65R;S68G 43;48 47;52 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Prior to ART, the lowest and highest prevalence of the S68G mutation were reported in subtype G (1.3%, n = 1564) and CRF01_AE (7.3%, n = 14,336), respectively. 2020 BMC infectious diseases Result HIV S68G 55 59 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. S68G mutation compensated for the replication fitness of the K65R mutation. 2020 BMC infectious diseases Result HIV K65R;S68G 61;0 65;4 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. S68G mutation does not decrease the drug susceptibility of the K65R mutation to AZT, TDF, or 3TC. 2020 BMC infectious diseases Result HIV K65R;S68G 63;0 67;4 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. S68G mutation is often selected on the basis of the K65R mutation. 2020 BMC infectious diseases Result HIV K65R;S68G 52;0 56;4 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Surprisingly, the S68G mutation showed a high tendency to coincide with the K65R mutation in various subtypes. 2020 BMC infectious diseases Result HIV K65R;S68G 76;18 80;22 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The frequency of the K65R mutation in patient 301635 was insufficient to select clones of the K65R/S68G double mutation; hence, this patient was not included in subsequent analyses. 2020 BMC infectious diseases Result HIV K65R;K65R;S68G 21;94;99 25;98;103 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The other two patients (301770 and 301844) had the predominant quasispecies carrying the K65R mutation at 3-6 months post ART (accounting for 95.38 and 92.51%, respectively). 2020 BMC infectious diseases Result HIV K65R 89 93 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The prevalence of the K65R/S68G double mutation among RTI-treated patients of various subtypes ranged from 21.1% (4/19) in subtype F to 61.7% (142/230) in CRF01_AE (Additional file 3: Table S2). 2020 BMC infectious diseases Result HIV K65R;S68G 22;27 26;31 RT 54 57 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The S68G mutation occurred at 77.52 and 59.19% respectively. 2020 BMC infectious diseases Result HIV S68G 4 8 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The viruses harboring the K65R/S68G double mutation in patients 301770, 301844, and 302335 exhibited a FC to AZT of 0.562 +- 0.067, 1.483 +- 0.529, and 1.359 +- 0.137, respectively. 2020 BMC infectious diseases Result HIV K65R;S68G 26;31 30;35 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Therefore, clones of the K65R/S68G double mutation and K65R mutation from the other three patients were used for analyses of phenotypic drug resistance. 2020 BMC infectious diseases Result HIV K65R;K65R;S68G 25;55;30 29;59;34 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. These values were not significantly different from those of the K65R mutation (FC: 0.925 +- 0.214, 1.262 +- 0.618, and 0.793 +- 0.09, respectively; p > 0.05). 2020 BMC infectious diseases Result HIV K65R 64 68 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Unlike the above three patients, patient 301635 carried the S68G mutation as the predominant natural polymorphism, appearing in > 90% of the quasispecies prior to ART. 2020 BMC infectious diseases Result HIV S68G 60 64 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Virus stocks of the K65R and K65R/S68G mutations were mixed with different input ratios and cultured for 13 days. 2020 BMC infectious diseases Result HIV K65R;K65R;S68G 20;29;34 24;33;38 32048186 Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV-1. It not only inhibited replication of HIV-1 laboratory strains (HIV-1IIIB), but also inhibited T20-resistant strains (pNL4-3gp41(36G)V38E,N42S and pNL4-3gp41(36G)V38A,N42T) that those compounds showed strong inhibitory activities against all T20-resistant strains with EC50 values about 10 ng/mL. 2020 Natural products and bioprospecting Result HIV N42S;N42T;V38A;V38E 137;166;160;131 141;170;165;136 32048186 Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV-1. Thus, the inhibition assay of microtiter syncytium formation of the two T20-resistant HIV-1 strains, pNL4-3gp41(36G)V38E,N42S and pNL4-3gp41(36G)V38A,N42T in C8166 cells, were used to evaluate anti-HIV activity, respectively. 2020 Natural products and bioprospecting Result HIV N42S;N42T;V38A;V38E 121;150;144;115 125;154;149;120 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. One therapy-naive patient showed evidence of drug resistance with D67N and T69N NRTI mutations. 2020 Medicine Result HIV D67N;T69N 66;75 70;79 NRTI 80 84 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. The predominant major NRTI mutation was M184I/V, while K103N was the predominant NNRTI mutation (Table 2). 2020 Medicine Result HIV K103N;M184I;M184V 55;40;40 60;47;47 NNRTI;NRTI 81;22 86;26 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. A previous X-ray structure for HIV-1 RT with HBV-associated septuple amino acid substitutions, which includes F160L, suggests that Leu160 renders the hollow shallower and may lead to a decrease in fitness mediated by 4'-ethynyl. 2020 Scientific reports Result HIV F160L 110 115 RT 37 39 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Because HIV3MB/F160M/M184V remains susceptible to ISL, we suspect that Met160 does not interfere with the binding of 4'-ethynyl. 2020 Scientific reports Result HIV F160M;M184V 15;21 20;26 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Bound 3TC-TP is misaligned in the N-site of RT3MB/F160M/M184V due to Val184 Cgamma1. 2020 Scientific reports Result HIV F160M;M184V 50;56 55;61 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. However, in the HBV RT sequence, the corresponding residue is Leu180, although the F160L mutation renders the virus replication-incompetent, thus eliminating the possibility of measuring the effects of F160L on susceptibility to ISL. 2020 Scientific reports Result HIV F160L;F160L 83;202 88;207 RT 20 22 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. However, we found that multiple mutations, including F160L, significantly compromised viral replicability; therefore, we were unable to perform an antiviral assay to verify drug susceptibility and resistance of the mutants. 2020 Scientific reports Result HIV F160L 53 58 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Importantly, we found that additional mutations F160M/M184V in RT rendered HIV3MB virtually fully resistant to both 3TC and ETV (Table 2). 2020 Scientific reports Result HIV F160M;M184V 48;54 53;59 RT 63 65 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. In fact, M184V in HIV-1 (or M204V in HBV) is not reportedly associated with TDF/TAF resistance. 2020 Scientific reports Result HIV M184V 9 14 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. In the present study, we showed that the susceptibility of HIV-1 carrying mutant RTs with M184V (HIV-13MB/M184V and HIV3MB/F160M/M184V) to TAF was substantially reduced (Table 2). 2020 Scientific reports Result HIV F160M;M184V;M184V;M184V 123;129;90;106 128;134;95;111 RT 81 84 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. M184V/I in HIV-1 RT has long been known as a critical 3TC-resistant-associated mutation in HIV-1. 2020 Scientific reports Result HIV M184I;M184V 0;0 7;7 RT 17 19 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Of these various HBV-mimicking HIV-1 RT mutants, we found that one with triple mutations (HIV-1 RTF115Y/Y116F/Q151M) was suitable for exploring the 3TC/ETV resistant mechanism, since replication-competent HIV-1F115Y/Y116F/Q151M exhibits substantial 3TC/ETV susceptibility, compared with HIV-1Q151M and HIV-1WT. 2020 Scientific reports Result HIV F115Y;Q151M;Q151M;Y116F;Y116F;Q151M 98;110;222;104;216;292 103;115;227;109;221;297 RT;RT 37;96 39;98 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. One possible solution to overcome M184V/I (M204V/I in HBV) resistance is to decrease composition for NRTIs that do not rely on the interactions with Met184. 2020 Scientific reports Result HIV M184I;M184V 34;34 41;41 NRTI 101 106 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. S4), indicating loose binding of 3TC-TP to RT3MB/F160M/M184V. 2020 Scientific reports Result HIV F160M;M184V 49;55 54;60 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. The structural superimposition of RT3MB/F160M/M184V and RT3MB also showed that both the methylene C44 of ETV-TP and the sulfur of 3TC-TP are located 2.8-3.0 A from Cgamma1 of Val184, indicating a severe steric clash. 2020 Scientific reports Result HIV F160M;M184V 40;46 45;51 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Therefore, we chose three corresponding mutations, M184V, F160M, and Q182G, in HIV-1 RT to investigate resistance to 3TC/ETV in HIV-1F115Y/Y116F/Q151M to 3TC and ETV. 2020 Scientific reports Result HIV Q151M;Y116F;F160M;M184V;Q182G 145;139;58;51;69 150;144;63;56;74 RT 85 87 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. These interactions may contribute to enzymatic stability of HIV-1 RT, and thus Q182G is unlikely to be suitable for helping understand the mechanism of HBV's resistance to 3TC and ETV due to S202G in HBV RT. 2020 Scientific reports Result HIV Q182G 79 84 RT;RT 66;204 68;206 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Thus, a M184V/I steric clash would likely occur when 3TC-TP tightly binds to the N-site, as observed in this study. 2020 Scientific reports Result HIV M184I;M184V 8;8 15;15 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Thus, a nearly identical ETV/3TC resistance mechanism appears to work for resistance to ETV and 3TC with M184I. 2020 Scientific reports Result HIV M184I 105 110 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Thus, it is apparent that the HIV-1 RT mutants with ETV-associated drug resistant mutation (M184V) presented in this study may not precisely reproduce the binding mode of TDF/TAF to HIV-1 RT with M184V, suggesting the imperfection of the present HBV RT model. 2020 Scientific reports Result HIV M184V;M184V 92;196 97;201 RT;RT;RT 36;188;250 38;190;252 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. To experimentally explore the structural effects of the Met184 substitution with Val/Ile, we also determined the HIV-1 RT3MB/F160M/M184V:DNA:3TC-TP ternary complex structure at a resolution of 2.57 A (Table 3). 2020 Scientific reports Result HIV F160M;M184V 125;131 130;136 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We confirmed previous reports that HIVQ151M and HIV3MB were substantially susceptible to ETV and 3TC, but significantly less susceptible to AZT due to Q151M and F116Y mutations, which are components of the well-known multi-drug resistance Q151M-complex. 2020 Scientific reports Result HIV F116Y;Q151M;Q151M 161;151;239 166;156;244 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We found that HIV3MB/F160M/Q182G/M184V failed to replicate, while the remaining four variants were replication-competent, suggesting that the Q182G mutation is detrimental for HIV-1 replication. 2020 Scientific reports Result HIV F160M;M184V;Q182G;Q182G 21;33;27;142 26;38;32;147 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We found that two RT molecules in the asymmetric unit were in different conformations: one in a closed conformation identical to other RT3MB ternary complexes, whereas the other molecule was in an open conformation reported previously for the RTQ151M:DNA binary complex structure. 2020 Scientific reports Result HIV Q151M 245 250 RT;RT 18;243 20;245 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We next performed an antiviral assay for HIVQ151M, HIV3MB, HIV3MB/M184V and HIV3MB/F160M/M184V, using ETV, 3TC, tenofovir alafenamide (TAF), islatravir (ISL; EFdA) and azidothymidine (AZT). 2020 Scientific reports Result HIV F160M;M184V;M184V 83;89;66 88;94;71 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We prepared HIV-1 mutants with HBV-associated amino acid substitutions Q151M (HIVQ151M), F115Y/Y116F/Q151M (HIV3MB), 3MB and M184V (HIV3MB/M184V), 3MB and F160M/M184V (HIV3MB/F160M/M184V), and 3MB and F160M/Q182G/M184V (HIV3MB/F160M/Q182G/M184V), and examined their viral replication kinetics (Table 1). 2020 Scientific reports Result HIV F115Y;F160M;F160M;F160M;M184V;M184V;M184V;Q151M;Q182G;Q182G;Y116F;F160M;M184V;M184V;M184V;Q151M 89;175;201;227;181;213;239;101;207;233;95;155;125;139;161;71 94;180;206;232;186;218;244;106;212;238;100;160;130;144;166;76 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Among them, the known DRMs Y181C and G190S showed the strongest correlation (cKa/KsY181C-G190S = 22.86, LOD = infinity). 2020 BMC infectious diseases Result HIV G190S;G190S;Y181C;Y181C 37;89;27;83 42;94;32;88 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. For the second case, 100% of sequences carried both Y181C and L228R simultaneously while, for the third case, 80% of sequences carried both Y181C and L228R simultaneously, and the remaining 20% carried only Y181C. 2020 BMC infectious diseases Result HIV L228R;L228R;Y181C;Y181C;Y181C 62;150;52;140;207 67;155;57;145;212 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. In this study, 40 out of 2034 (1.97%) treatment-naive CRF01_AE-infected patients had transmitted DRMs, with the common DRMs comprising K103 N, G190S, K101E, T215S, K65R, and K219Q. 2020 BMC infectious diseases Result HIV G190S;K101E;K103N;K219Q;K65R;T215S 143;150;135;174;164;157 148;155;141;179;168;162 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. It was noted that an unknown mutation (V75 L) was detected at site 75, a drug resistance-associated site, which increased from 4.8% at baseline to 16.7% at TF time point (Z value = 2.494, p < 0.05; p McNemar test = 0.008). 2020 BMC infectious diseases Result HIV V75L 39 44 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. L228R occurred simultaneously or followed the appearance of Y181C. 2020 BMC infectious diseases Result HIV Y181C;L228R 60;0 65;5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. L228R was correlated with known DRMs G190S (cKa/KsL228R-G190S = 2.25, LOD = infinity) and K65R (cKa/KsK65R-L228R = 2.00, LOD = 3.46), and strongly correlated with Y181C (cKa/KsY181C-L228R = 6.00, LOD = 4.09) (Table 2). 2020 BMC infectious diseases Result HIV G190S;G190S;K65R;K65R;L228R;L228R;L228R;Y181C;Y181C;L228R 37;56;90;102;107;182;50;163;176;0 42;61;94;106;112;187;55;168;181;5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Moreover, a new mutation (L228R) was detected at site 228, a non-DRM site in the Stanford HIVdb algorithm, which increased from 0% at baseline to 11.9% at TF time point (Z value = 2.306, p < 0.05; p McNemar test = 0.063). 2020 BMC infectious diseases Result HIV L228R 26 31 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Nine known DRMs (K65R, V106 M, Y115F, V179 T/E/D, Y181C, M184 V, and G190S) and two potential new DRMs (V75 L and L228R) were demonstrated to be under positive selection pressure (Ka/Ks > 1, LOD > 2). 2020 BMC infectious diseases Result HIV G190S;K65R;L228R;M184V;V106M;V179E;V179T;V75L;Y115F;Y181C 69;17;114;57;23;38;38;104;31;50 74;21;119;63;29;48;48;110;36;55 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The first case demonstrated a time lag between the Y181C and L228R mutations; Y181C occurred in 53.4% of the sequences at 1-month post treatment, which increased to 100% at 3 months post treatment, and L228R did not appear until 6 months post treatment, when 87.1% of sequences carried both Y181C and L228R mutations. 2020 BMC infectious diseases Result HIV L228R;L228R;L228R;Y181C;Y181C;Y181C 61;202;301;51;78;291 66;207;306;56;83;296 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The NNRTI-associated DRMs detected at TF time point included G190S/C (66.7%), K101E/N/Q (52.4%), V179D/I/A/T/E (45.2%), Y181C (42.9%), K103R/N/S (42.9%), and V106 M (23.8%) (Table 1). 2020 BMC infectious diseases Result HIV G190C;G190S;K101E;K101N;K101Q;K103N;K103R;K103S;V106M;V179A;V179D;V179E;V179I;V179T;Y181C 61;61;78;78;78;135;135;135;158;97;97;97;97;97;120 68;68;87;87;87;144;144;144;164;110;110;110;110;110;125 NNRTI 4 9 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The NRTI-associated DRMs detected at TF time point in descending order included K65R (57.1%), M184 V/I (47.6%), S68G (26.2%), A62V (14.3%), K70E/R (9.5%), and Y115F (9.5%). 2020 BMC infectious diseases Result HIV A62V;K65R;K70E;K70R;M184I;M184V;S68G;Y115F 126;80;140;140;94;94;112;159 130;84;146;146;102;102;116;164 NRTI 4 8 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The second and third cases had Y181C and L228R only at TF. 2020 BMC infectious diseases Result HIV L228R;Y181C 41;31 46;36 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. To further explore the temporal association and the evolutionary dynamics between Y181C and L228R, longitudinal plasma samples of four CRF01_AE-infected patients with Y181C and L228R mutations were studied using deep sequencing. 2020 BMC infectious diseases Result HIV L228R;L228R;Y181C;Y181C 92;177;82;167 97;182;87;172 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. V75 L was correlated with known DRMs G190S (cKa/KsV75L-G190S = 3.24, LOD = infinity), K65R (cKa/KsK65R-V75L = 2.00, LOD = 5.04), and M184 V (cKa/KsV75L-M184V = 1.25, LOD = 4.03). 2020 BMC infectious diseases Result HIV G190S;G190S;K65R;K65R;M184V;M184V;V75L;V75L;V75L 37;55;86;98;133;152;103;0;147 42;60;90;102;139;157;107;5;151 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. We speculated that both V75 L and L228R might be potential new DRMs in CRF01_AE. 2020 BMC infectious diseases Result HIV L228R;V75L 34;24 39;29 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. All sequences with L74I at consensus (27%, 31/115) had the trinucleotide ATA at this position. 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 19 23 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Considering the first timepoint at which L74I was detected for each participant, the median frequency of L74I was 90.6% (IQR = 17.8-98.7). 2020 The Journal of antimicrobial chemotherapy Result HIV L74I;L74I 41;105 45;109 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Eight participants had L74I as the majority allele (>85% frequency) in every sample (Table 2). 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 23 27 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Forty-six (40%) of the participants had L74I detected at >2% frequency in at least one plasma sample. 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 40 44 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Four had low-level minority variants of less than 10% frequency and in two of these L74I was not detected in the preceding plasma samples. 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 84 88 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Four had T97A [this was the consensus in three of them and a minority variant in one (who also had L74I)], another participant had an E138K minority variant and another had a G140A minority variant. 2020 The Journal of antimicrobial chemotherapy Result HIV E138K;G140A;L74I;T97A 134;175;99;9 139;180;103;13 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The most common integrase polymorphism was E157Q, which was detected in 12 participants (6 of these also had L74I). 2020 The Journal of antimicrobial chemotherapy Result HIV E157Q;L74I 43;109 48;113 IN 16 25 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The participant characteristics of those with and without an L74I mutation were similar, with an overall median age of 30 years, two-thirds were female and the median CD4 cell count at first-line VF was 142 cells/mm3 (IQR = 64-246) (see Table 1). 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 61 65 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The remaining 73.9% (34/46) had L74I present at >20% frequency (the usual Sanger sequencing threshold of detection). 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 32 36 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The remaining consensus sequences were all L74L. 2020 The Journal of antimicrobial chemotherapy Result HIV L74L 43 47 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. The trinucleotides CTG or TTG were the consensus codon in 60% (69/115), requiring two nucleotide changes to result in an amino acid substitution from leucine to isoleucine, and 13% (15/115) had either TTA or CTA, requiring only one nucleotide change to mutate to L74I. 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 263 267 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. There was a similar frequency of L74I among the subtypes, with a median frequency of 93.0% (IQR = 26.9-99.0) in CRF02_AG and 89.2% (IQR = 8.1-98.2) (P = 0.62) in subtype G. 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 33 37 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. There was a subtype difference in L74I prevalence, with 55.3% (26/47) of participants with subtype G infection having the L74I mutation detected in at least one plasma sample, compared with 29.4% (20/68) of those with CRF02_AG infection (P = 0.005). 2020 The Journal of antimicrobial chemotherapy Result HIV L74I;L74I 34;122 38;126 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. There was no significant subtype difference in the number of substitutions required to mutate from L74L to L74I (P = 0.13). 2020 The Journal of antimicrobial chemotherapy Result HIV L74I;L74L 107;99 111;103 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. This comprised 4 participants with 20%-50% frequency, 6 with 50%-90% frequency and 24 in whom L74I was fixed at >90% frequency at that position. 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 94 98 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Two had Q148K and two had R263K minority variants (one of whom also had L74I). 2020 The Journal of antimicrobial chemotherapy Result HIV L74I;Q148K;R263K 72;8;26 76;13;31 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Two participants had reversion to low (<2%) or no L74I in subsequent samples. 2020 The Journal of antimicrobial chemotherapy Result HIV L74I 50 54 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. A significantly higher proportion of AG database samples (21%) had the L74M mutation compared to 4.2% in database non-AG samples (p < 0.005, Table 4). 2020 International journal of molecular sciences Result HIV L74M 71 75 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. A significantly higher proportion of non-AG database samples (86.56%) had the M50I mutation compared to 17.6% in database AG samples (p < 0.000001, Table 4). 2020 International journal of molecular sciences Result HIV M50I 78 82 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Analysis of the 215 database samples showed 29 samples with mutations in the viral 3'-PPT region [G9078T in one subtype F2 and one Group O; A9075T in two HIV-1 group N samples; G9081A in one HIV-1 CRF_36cpx, one HIV-1 group M/O recombinant, one HIV-1 group P, and 21 HIV-1 group O; A9071G mutation in one HIV-1 CRF02_AG sample] (Figure 5). 2020 International journal of molecular sciences Result HIV A9071G;A9075T;G9078T;G9081A 282;140;98;177 288;146;104;183 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. E157Q and S119R mutations were observed only in cohort samples of AG subtype. 2020 International journal of molecular sciences Result HIV S119R;E157Q 10;0 15;5 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. For the cohort group, polymorphisms A21T, I72V, D167E, and D256E were significantly more prevalent in non-AG (24-48%) than in AG (5-20%) samples (p < 0.04, Table 5) and K136Q was only present in non-AG (44%) samples (p < 0.000001, Table 5). 2020 International journal of molecular sciences Result HIV A21T;D167E;D256E;I72V;K136Q 36;48;59;42;169 40;53;64;46;174 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Four other mutations were identified in cohort samples: M50I (in 6 samples), S119R (in 4 samples, all CRF02_AG), L74M (in 8 CRF02_AG and 1 CRF11_cpx samples), and L74I in 25 samples of which 22 (88%) were CRF02_AG (Table 2). 2020 International journal of molecular sciences Result HIV L74I;L74M;M50I;S119R 163;113;56;77 167;117;60;82 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Integrase polymorphisms in both cohort and database samples: Overall, T124A, G134N, I135V, K136T, T206S, and R269K polymorphisms were significantly more prevalent in AG compared to non-AG samples, whereas A21T, K136Q, D167E, and D256E polymorphisms were significantly more prevalent in non-AG compared to AG samples. 2020 International journal of molecular sciences Result HIV A21T;D167E;D256E;G134N;I135V;K136Q;K136T;R269K;T124A;T206S 205;218;229;77;84;211;91;109;70;98 209;223;234;82;89;216;96;114;75;103 IN 0 9 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Integrase polymorphisms in cohort samples: Comparative analyses of cohort subjects infected with CRF02_AG and non-AG subtypes showed that the G134N, I135V, K136T, and T206S polymorphisms were present in a significantly higher proportion of samples with AG subtype (81% to 97%) compared to samples with non-AG subtypes (28-52%) (p < 0.00001, Table 5). 2020 International journal of molecular sciences Result HIV G134N;I135V;K136T;T206S 142;149;156;167 147;154;161;172 IN 0 9 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Integrase polymorphisms in database samples: The L101I, T125A, G134N, I135V, K136T, T206S, T218I, and R269K polymorphisms were present in a significantly higher proportion of AG (44% to 95%) compared to non-AG (5-66%) database samples (p < 0.00002, Table 5). 2020 International journal of molecular sciences Result HIV G134N;I135V;K136T;L101I;R269K;T125A;T206S;T218I 63;70;77;49;102;56;84;91 68;75;82;54;107;61;89;96 IN 0 9 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Mutation downstream of the 3'-PPT (LTR) was only observed in one database sample (T9086G in one Group N sample) (Figure 5). 2020 International journal of molecular sciences Result HIV T9086G 82 89 LTR 35 38 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Mutations within the 15 nucleotides 3'-PPT region (Figure 4, yellow highlight) was observed only in 2 cohort samples: A9076C mutation in subject NACMR185 and A9071G mutation in subject NACMR086 (Figure 4). 2020 International journal of molecular sciences Result HIV A9071G;A9076C 158;118 164;124 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Other mutations in database samples included M50I, L74M, L74I, S119R, S230N, and E138D, identified in 67 (31%), 9 (4%), 49 (22.8%), 1 (0.47%), 2 (0.93%), and 1 (0.47%) of database samples (Table 3), respectively. 2020 International journal of molecular sciences Result HIV E138D;L74I;L74M;M50I;S119R;S230N 81;57;51;45;63;70 86;61;55;49;68;75 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Seven database samples had mutations upstream of the 3'-PPT region (C9063T in one Group O and 5 group M [3 CRF02_AG and 2 subtypes A1]; C9063A in one subtype D) (Figure 5). 2020 International journal of molecular sciences Result HIV C9063A;C9063T 136;68 142;75 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Similarly, K14R, V31I, T112V, and T214A polymorphisms were present in a significantly higher proportion of AG (75% to 95%) than non-AG (50% to 78%) database samples (Table 5). 2020 International journal of molecular sciences Result HIV K14R;T112V;T214A;V31I 11;23;34;17 15;28;39;21 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Similarly, T124A was present in a higher proportion of AG (90.67%) than non-AG (68%) samples (p = 0.031, Table 5), and R269K was only present in AG (30.67%) samples (p = 0.003, Table 5). 2020 International journal of molecular sciences Result HIV R269K;T124A 119;11 124;16 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The E11D, A21T, G134D, K136Q, D167E, I208L, and D256E polymorphisms were significantly more prevalent in non-AG (14'51.3%) than in AG (3-26%) database samples (Table 5). 2020 International journal of molecular sciences Result HIV A21T;D167E;D256E;E11D;G134D;I208L;K136Q 10;30;48;4;16;37;23 14;35;53;8;21;42;28 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The INSTIs accessory RAMs E157Q and T97A were present, respectively, in 6 (all CRF02_AG) and 2 (1 CRF02_AG and 1 CRF09_cpx) samples (Table 2). 2020 International journal of molecular sciences Result HIV E157Q;T97A 26;36 31;40 INSTI 4 10 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The INSTIs accessory RAMs identified in both AG and AG database samples included T97A, E157Q, M50I, L74M, L74I, and S230N (in 3.5% to 60% of AG and in 1.4% to 86.5% of non-AG database samples). 2020 International journal of molecular sciences Result HIV E157Q;L74I;L74M;M50I;S230N;T97A 87;106;100;94;116;81 92;110;104;98;121;85 INSTI 4 10 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The INSTIs accessory RAMs identified in both cohort and database samples included T97A, E157Q, M50I, L74M, L74I, and S119R. 2020 International journal of molecular sciences Result HIV E157Q;L74I;L74M;M50I;S119R;T97A 88;107;101;95;117;82 93;111;105;99;122;86 INSTI 4 10 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The INSTIs accessory RAMs identified in both HIV-1 CRF02_AG and non-AG cohort samples included T97A, M50I, L74M, and L74I (in 1.3% to 29.3% of AG and in 4% to 16% of non-AG cohort samples). 2020 International journal of molecular sciences Result HIV L74I;L74M;M50I;T97A 117;107;101;95 121;111;105;99 INSTI 4 10 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The proportion of AG and non-AG database samples harboring other INSTIs RAMs was not significantly different and T66A, N155K, A128T, S119R, and S230N were observed only in a very small number (1.4%) of database samples of non-AG genotypes (Table 4). 2020 International journal of molecular sciences Result HIV A128T;N155K;S119R;S230N;T66A 126;119;133;144;113 131;124;138;149;117 INSTI 65 71 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Three INSTIs accessory RAMs were identified: T97A (in 16 samples), A128T (in 1 M/O recombinant sample), and E157Q (in 3 samples) (Table 3). 2020 International journal of molecular sciences Result HIV A128T;E157Q;T97A 67;108;45 72;113;49 INSTI 6 12 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Two INSTIs major RAMs were identified in two database samples: T66A in 1 (0.47%) HIV-1 group M/O recombinant sample isolated in 1997 from a 29 years old ART-naive Cameroonian female (GenBank accession number: AJ239083); and N155K in 1 (0.47%) CRF36_cpx sample isolated in 2000 from a 19 years old female in Cameroon (GenBank accession number: EF087995) (Table 3). 2020 International journal of molecular sciences Result HIV N155K;T66A 224;63 229;67 INSTI 4 10 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. Compounds with 3-F (10c-p) displayed better activity than the marketed drug 3TC on mutant E138K except for 10h and 10i. 2020 Molecules (Basel, Switzerland) Result HIV E138K 90 95 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. However, in the Y188L RT (Figure 4H), the compound 10p lost the hydrogen bond between 4'-CN and Y188 and decreased pi-pi stacking interactions. 2020 Molecules (Basel, Switzerland) Result HIV Y188L 16 21 PI;PI;RT 115;118;22 117;120;24 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. In the E138K RT (Figure 4G), the binding mode was similar to the WT RT. 2020 Molecules (Basel, Switzerland) Result HIV E138K 7 12 RT;RT 13;68 15;70 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. Most compounds showed submicromolar activities against E138K, Y181C, K103N, and L100I variants. 2020 Molecules (Basel, Switzerland) Result HIV E138K;K103N;L100I;Y181C 55;69;80;62 60;74;85;67 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. Notably, compound 10p exhibited the best EC50 values of 0.17, 0.87, 0.90, and 1.21 microM against the single mutant strains E138K, Y181C, K103N, and L100I, especially for the mutant strains of E138K, Y181C, and K103N, which were more active than the reference drugs NVP and 3TC. 2020 Molecules (Basel, Switzerland) Result HIV E138K;E138K;K103N;K103N;L100I;Y181C;Y181C 124;193;138;211;149;131;200 129;198;143;216;154;136;205 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. That might explain the higher antiviral activity against the E138K mutant than against the Y188L mutant. 2020 Molecules (Basel, Switzerland) Result HIV E138K;Y188L 61;91 66;96 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. The binding modes of 10p with double mutant (F227L + V106A, K103N + Y181C) RT were also predicted (see Figure S1, Supplementary Materials). 2020 Molecules (Basel, Switzerland) Result HIV F227L;K103N;V106A;Y181C 45;60;53;68 51;65;58;73 RT 75 77 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. The pi-pi stacking interactions were reduced by Y181C and F227L mutations with decreased aromatic rings. 2020 Molecules (Basel, Switzerland) Result HIV F227L;Y181C 58;48 63;53 PI;PI 4;7 6;9 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. These compounds were also tested in the MT-4 cells for their activities against the single mutant (L100I, E138K, Y181C, K103N, Y188L) and double RT mutant (K103N + Y181C, F227L + V106A) HIV-1 strains (Table 2). 2020 Molecules (Basel, Switzerland) Result HIV E138K;F227L;K103N;K103N;L100I;V106A;Y181C;Y181C;Y188L 106;171;120;156;99;179;113;164;127 111;176;125;162;104;184;118;169;132 RT 145 147 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. They were more sensitive toward E138K and less active against Y188L. 2020 Molecules (Basel, Switzerland) Result HIV E138K;Y188L 32;62 37;67 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. Unfortunately, these compounds were devoid of satisfactory activity against HIV-1 double mutants (K103N + Y181C, F227L + V106A). 2020 Molecules (Basel, Switzerland) Result HIV F227L;K103N;V106A;Y181C 113;98;121;106 118;104;126;111 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. From analysis of these integrase sequences, no primary mutations (Y143R=C=H, Q148H=R=K, and N155H=S) associated with reduced susceptibility to the integrase inhibitors Raltegravir and Elvitegravir were detected. 2020 Ethiopian journal of health sciences Result HIV N155H;Q148H;Y143R 92;77;66 97;82;72 IN;IN 23;147 32;156 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. These mutations were M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%). 2020 Ethiopian journal of health sciences Result HIV E157Q;E92G;G140A;G140C;G140S;M50I;S153G;S153Y;T97A 90;56;69;69;69;21;48;48;35 95;60;78;78;78;25;54;54;39 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. D67E is a non-polymorphic mutation that generally occurs in viruses with multiple TAMs. 2020 PloS one Result HIV D67E 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. D67N is a non-polymorphic thymidine analog mutation (TAM) associated with low-level resistance to AZT and Stavudine (D4T). 2020 PloS one Result HIV D67N 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. In the present study, SDRMs belonged to the NRTIs class including D67N and D67E, which were found in two patients. 2020 PloS one Result HIV D67E;D67N 75;66 79;70 NRTI 44 49 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. It was also observed that the SDRMs belonged to the NNRTIs class including K103N and V106A detected in three patients. 2020 PloS one Result HIV K103N;V106A 75;85 80;90 NNRTI 52 58 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K103N is a non-polymorphic mutation that induces high-level reductions in the susceptibility to Nevirapine (NVP) and Efavirenz (EFV). 2020 PloS one Result HIV K103N 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. The most common mutations were M46I and I47V for PIs, M184V for NRTIs, and K103N/S for NNRTIs (Table 6). 2020 PloS one Result HIV I47V;K103N;K103S;M184V;M46I 40;75;75;54;31 44;82;82;59;35 NNRTI;NRTI;PI 87;64;49 93;69;52 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. Three minor HIV protease inhibitor-related mutations (L10I, L10V, and G73S) were also detected in four patients, although these mutations are not included in the WHO SDRMs list (Table 4). 2020 PloS one Result HIV G73S;L10I;L10V 70;54;60 74;58;64 PR 16 24 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V106A is a non-polymorphic mutation that can cause high-level resistance to Nevirapine (NVP) and intermediate resistance to Efavirenz (EFV). 2020 PloS one Result HIV V106A 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V106A is associated with high-level resistance to DOR when accompanied by other DOR-associated DRMs. 2020 PloS one Result HIV V106A 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. N169D in the V1V2 region also caused an added negative charge, like K187E. 2020 Pathogens (Basel, Switzerland) Result HIV K187E;N169D 68;0 73;5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Notably, the IC50 of the consensus MK1+ENTA with N169D was >50 microg mL-1, similar to that of #818 against KD247. 2020 Pathogens (Basel, Switzerland) Result HIV N169D 49 54 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. reported that the amino acid substitutions in the V2 region in the 14 MK38 clones were N169D, K187E, and S190N. 2020 Pathogens (Basel, Switzerland) Result HIV K187E;N169D;S190N 94;87;105 99;92;110 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Then, env consensus mutants for MK1 were generated using a mutagenesis method: MK1+K187E (E), MK1+K187E+S190N (EN), MK1+K187E+S190N+A389T (ENT), and MK1+K187E+S190N+A389T+ T437A (ENTA). 2020 Pathogens (Basel, Switzerland) Result HIV K187E;K187E;K187E;K187E;A389T;A389T;S190N;S190N;S190N;T437A 83;98;120;153;132;165;104;126;159;172 88;103;125;158;137;170;109;131;164;177 Env 6 9 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Therefore, N169D is a key substitution for acquiring neutralisation resistance. 2020 Pathogens (Basel, Switzerland) Result HIV N169D 11 16 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Therefore, we added N169D to the consensus MK1+ENTA using a mutagenesis method. 2020 Pathogens (Basel, Switzerland) Result HIV N169D 20 25 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Therefore, we generated DENT (MK1env+N169D+K187E+S190N+A389T), DEN, DNT, DE, DN, DT, and D to determine which mutations are important for neutralisation resistance against KD247 when combined with N169D. 2020 Pathogens (Basel, Switzerland) Result HIV A389T;K187E;N169D;N169D;S190N 55;43;37;197;49 60;48;42;202;54 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. We also added N169D to the other consensus MK1s (i.e., MK1+E, MK1+EN, MK1+ENT, and MK1+ENTA), including in various different combinations to obtain resistant MK1 with minimal mutations, including 169D. 2020 Pathogens (Basel, Switzerland) Result HIV N169D 14 19 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. We also tested neutralisation resistance against KD247 with other substitutions, i.e., N133S, S147G, N169D, N237T, D282N, S294F, T437A, and T463P with MK1, but did not see any difference from the consensus MK1s (<10 microg mL-1; data not shown). 2020 Pathogens (Basel, Switzerland) Result HIV D282N;N133S;N169D;N237T;S147G;S294F;T437A;T463P 115;87;101;108;94;122;129;140 120;92;106;113;99;127;134;145 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. We analysed the sequence variation of the MK38 strain and identified four majority consensus mutations in the 13 substitutions in the #818 clone: K187E, S190N, A389T, and T437A. 2020 Pathogens (Basel, Switzerland) Result HIV A389T;K187E;S190N;T437A 160;146;153;171 165;151;158;176 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. While the IC50 of MK1 was 0.5 microg mL-1, that of MK1+ N169D was 17 microg mL-1. 2020 Pathogens (Basel, Switzerland) Result HIV N169D 56 61 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. Based on the results of the first round of screening, we performed further antiviral activity evaluation of I-11 and I-12 as representative compounds and assessed the activity against different HIV-1 strains including wild-type strains (HIV-1IIIB and HIV-1Ba-L), resistant strains (HIV-1A17, HIV-174V and HIV-1RF/V82F/184V) and clinical isolated strains (HIV-1TC-1 and HIV-1WAN). 2020 Acta pharmaceutica Sinica. B Result HIV V82F 313 317 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. Compared to DB02, the cyclohexyl group of I-11 extended deeper into this region and formed arene-H with the indol ring of conserved amino acid Trp229 which might be the main reason of giving rise to the high-affinity binding to the NNBIP improving the anti-HIV-1 activity and prevented the loss of activity specifically caused by Y181C mutation. 2020 Acta pharmaceutica Sinica. B Result HIV Y181C 330 335 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. However, for HIV-1A17, a multi-drug resistant strain of NNRTIs carrying the K103N and Y181C mutations, I-11, I-12 and DB02 all showed a significantly reduced inhibitory activity with EC50 values of 2.77, 4.87 and 6.01 mumol/L. 2020 Acta pharmaceutica Sinica. B Result HIV K103N;Y181C 76;86 81;91 NNRTI 56 62 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. Since the new generation of NNRTI, etravirine, showed a better inhibitory activity against K103N/Y181C double mutant HIV-1 strain (EC50=0.050 mumol/L), more improvements will be required to our compounds. 2020 Acta pharmaceutica Sinica. B Result HIV K103N;Y181C 91;97 96;102 NNRTI 28 33 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Compared to HIV-GFP, the N74D mutation delayed the process of uncoating and increased the half-life of uncoating to 141 min compared to 62 min for wildtype. 2020 Virology journal Result HIV N74D 25 29 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Finally, A92E mutant virus had an uncoating half-life of 62 min that was not statistically different from the 52 min for wildtype. 2020 Virology journal Result HIV A92E 9 13 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. However, if there was a differential effect of cyclosporin A on N74D virus over time, this effect could bias the normalized uncoating kinetics. 2020 Virology journal Result HIV N74D 64 68 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. In HeLa cells CsA treatment has been shown to decrease the infectivity of N74D mutant virus, but not virus with a wildtype capsid. 2020 Virology journal Result HIV N74D 74 78 Capsid 123 129 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Some alterations in completion of reverse transcription were observed, with A92E seeming to reverse transcribe at the greatest rate and E45A at the slowest rate. 2020 Virology journal Result HIV A92E;E45A 76;136 80;140 RT 34 55 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The E45A mutation also delayed the process of uncoating compared to wildtype, with an average half-life of 102 min compared to 50 min for wildtype. 2020 Virology journal Result HIV E45A 4 8 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Therefore, we examined the effect of CsA on wildtype and N74D infectivity in the parent CHME3 cell line over time by performing a CsA washout assay. 2020 Virology journal Result HIV N74D 57 61 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. This E45A/R123T mutant virus uncoated with kinetics like wildtype, with an average half-life of uncoating of 39 min that was not statistically different from the average half-life of 43 min for wildtype in parallel experiments. 2020 Virology journal Result HIV E45A;R123T 5;10 9;15 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Treatment with CsA decreased both wildtype and N74D infectivity at all time points examined compared to the ethanol control. 2020 Virology journal Result HIV N74D 47 51 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. We also examined the uncoating of virus containing the R132T second site suppressor mutation which partially restores the infectivity of E45A mutant virus. 2020 Virology journal Result HIV E45A;R132T 137;55 141;60 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. We previously examined the uncoating of a panel of CA mutant viruses in OMK cells and found that the N74D, A92E, and E45A mutations altered the rate of uncoating compared to wildtype. 2020 Virology journal Result HIV A92E;E45A;N74D 107;117;101 111;121;105 Capsid 51 53 32158555 Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy. Thirty-five (47%) of 74 samples were successfully sequenced, with 4 (11%) of 35 having a major drug resistance mutation: 2 with K103N and 2 with V106M (Table 1). 2020 Southern African journal of HIV medicine Result HIV K103N;V106M 128;145 133;150 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. The major mutations were I54L (3.83%), V82L (2.84%) and M46I/L (1.53%). 2020 Virology journal Result HIV I54L;M46I;M46L;V82L 25;56;56;39 29;62;62;43 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. The most common primary NRTI mutations detected included M184V (62.04%), K65R (20.24%), K70R (15.01%), T215D/S (9.41%), Y115F (7.22%) and M41L (6.35%). 2020 Virology journal Result HIV K65R;K70R;M184V;M41L;T215D;T215S;Y115F 73;88;57;138;103;103;120 77;92;62;142;110;110;125 NRTI 24 28 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. The most frequent mutations to NNRTIs were K103N (41.90%), Y181C (28.12%), G190A (26.48%), K101E (11.71%), V106M/A (10.94%), V108I (7.44%), 221Y (7.22%) and Y188H (5.91%).The proportion of PI-associated DRMs showed a tendency to increase from 2012 to 2017(0, 0, 0.22, 0.98, 1.86 and 3.81%). 2020 Virology journal Result HIV G190A;K101E;K103N;V106A;V106M;V108I;Y181C;Y188H 75;91;43;107;107;125;59;157 80;96;48;114;114;130;64;162 NNRTI;PI 31;189 37;191 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. The NNRTI (t)-associated mutation G190A emerged in 92.24% (202/219) of the subtype CRF01AE sequences and in 7.76% of other subtypes (p < 0.05). 2020 Virology journal Result HIV G190A 34 39 NNRTI 4 9 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. Y181C also emerged frequently in subtype CRF01AE sequences (71.60% vs 28.40% for other subtypes, p < 0.05). 2020 Virology journal Result HIV Y181C 0 5 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. As a control, we also challenged CD4+ T cells with increasing concentrations of HIV-1-P90A-GFP, an HIV-1 mutant that is completely inhibited in CD4+ T cells (Figures 4B and 4C). 2020 Cell reports Result HIV P90A 86 90 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. As expected, recombinant CypA did not affect the binding of TRIM5alphahu to HIV-1 cores bearing the P90A mutation. 2020 Cell reports Result HIV P90A 100 104 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. As expected, the integration of HIV-1-P90A and HIV-1-G89V was blocked. 2020 Cell reports Result HIV G89V;P90A 53;38 57;42 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. As shown in Figures 2C and S2B, we found that HIV-1-P90A-GFP infection was not inhibited in TRIM5alphahu KD cells compared with control cells. 2020 Cell reports Result HIV P90A 52 56 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Considering that HIV-1-P90A-GFP does not bind CypA protein but does bind TRIM5alphahu, these results demonstrate that TRIM5alphahu is the restriction factor blocking infection of primary CD4+ T cells by HIV-1-P90A viruses. 2020 Cell reports Result HIV P90A;P90A 23;209 27;213 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Consistent with our hypothesis, depletion of TRIM5alphahu expression completely rescued infection of HIV-1-P90A viruses (Figure 6B). 2020 Cell reports Result HIV P90A 107 111 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Consistent with our previous binding experiments, these experiments suggest that infection of CD4+ T cells by HIV-1-A92E-GFP or HIV-1-G94D-GFP was not affected by TRIM5alphahu, which correlated with the inability of TRIM5alphahu to bind to HIV-1 cores bearing the mutation A92E or G94D. 2020 Cell reports Result HIV A92E;G94D;A92E;G94D 273;281;116;134 277;285;120;138 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Consistent with our previous results, HIV-1-P90AGFP and HIV-1-G89V-GFP strains showed weak infection of CD4+ T cells (Figure S6A). 2020 Cell reports Result HIV G89V;P90A;P90F;P90G;P90P 62;44;44;44;44 66;48;51;51;51 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Consistent with these findings, we observed that HIV-1-A92EGFP infection of Jurkat cells was insensitive to CsA treatment (Figure S3). 2020 Cell reports Result HIV A92E;A92F;A92G;A92P 55;55;55;55 59;62;62;62 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Depletion of TRIM5alphahu Expression in Human CD4+ T Cells Rescues Infection by HIV-1-P90A Viruses. 2020 Cell reports Result HIV P90A 86 90 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Furthermore, endogenously expressed TRIM5alphahu also bound to stabilized HIV-1 capsid tubes bearing the P90A mutation (Figure 3E). 2020 Cell reports Result HIV P90A 105 109 Capsid 80 86 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. HIV-1-P90A-GFP is a mutant form of HIV-1 in which CypA-capsid interactions are disrupted during infection. 2020 Cell reports Result HIV P90A 6 10 Capsid 55 61 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. In addition, we show that HIV-1-A92E viruses do not exhibit a replication defect in primary CD4+ T cells in the absence or presence of CsA. 2020 Cell reports Result HIV A92E 32 36 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. In order to study the role of TRIM5alphahu during viral infection, we examined the ability of HIV-1-A92E-GFP and HIV-1-G94D-GFP to infect CD4+ T cells (Figures 4B and 4C). 2020 Cell reports Result HIV A92E;G94D 100;119 104;123 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Interestingly, reverse transcription was reduced for HIV-1-P90A-GFP and HIV-1-G89V-GFP, suggesting that CypA-capsid interactions were important for HIV-1 reverse transcription in CD4+ T cells. 2020 Cell reports Result HIV G89V;P90A 78;59 82;63 RT;RT;Capsid 15;154;109 36;175;115 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Mutant HIV-1 bearing the capsid change A92E or G94D lacks the ability to interact with TRIM5alphahu (Figure 3C). 2020 Cell reports Result HIV A92E;G94D 39;47 43;51 Capsid 25 31 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Our results show that TRIM5alphahu does not interact with A92E cores. 2020 Cell reports Result HIV A92E 58 62 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Overall, these results indicate that TRIM5alphahu does not bind to mutant HIV-1 capsids bearing the change A92E or G94D, which may explain the reason that CsA treatment does not affect the infection of Jurkat cells by HIV-1-A92E-GFP or HIV-1-G94DGFP viruses. 2020 Cell reports Result HIV A92E;G94D;A92E;G94D;G94F;G94G;G94P 107;115;224;242;242;242;242 111;119;228;246;249;249;249 Capsid 80 87 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Previous studies have shown that infection of Jurkat cells by the HIV-1 strain bearing the capsid mutation A92E or G94D was less sensitive to CsA treatment when compared with wild-type HIV-1. 2020 Cell reports Result HIV A92E;G94D 107;115 111;119 Capsid 91 97 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. This insensitivity may occur due to HIV-1-A92EGFP inability to interact with TRIM5alphahu. 2020 Cell reports Result HIV A92E;A92F;A92G;A92P 42;42;42;42 46;49;49;49 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. To explore this possibility, we tested whether TRIM5alphahu interacts with HIV-1 cores containing the A92E mutation. 2020 Cell reports Result HIV A92E 102 106 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. To further confirm the importance of CypA-capsid interactions in HIV-1 infection, we challenged Jurkat T cells with p24-normalized amounts of HIV-1-P90A-GFP and HIV-1-G89V-GFP, which are mutant versions of HIV-1 that disrupt CypA-capsid interactions. 2020 Cell reports Result HIV G89V;P90A 167;148 171;152 Capsid;Capsid;p24 42;230;116 48;236;119 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. To further corroborate these findings, we challenged human PBMCs and CD4+ T cells with increasing amounts of HIV-1-GFP particles bearing the capsid mutations P90A and G89V, both of which prevent CypA-capsid interactions. 2020 Cell reports Result HIV G89V;P90A 167;158 171;162 Capsid;Capsid 141;200 147;206 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. To test whether TRIM5alphahu blocks the infection of viruses that do not interact with CypA, we challenged TRIM5alphahu knockout CD4+ T cells with increasing amounts of HIV-1-P90A viruses. 2020 Cell reports Result HIV P90A 175 179 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. We also demonstrate that CsA does not affect the ability of HIV-1-A92E-GFP viruses to infect human primary CD4+ T cells (Figure 4D), suggesting that HIV-1-A92E-GFP viruses are insensitive to TRIM5alphahu. 2020 Cell reports Result HIV A92E;A92E 66;155 70;159 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. We also found that the binding of TRIM5alphahu to mutant P90A HIV-1 cores was 5- to 6-fold higher than that of wild-type HIV-1 cores (Figure 3A) in the absence of CsA. 2020 Cell reports Result HIV P90A 57 61 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. We found that HIV-1-P90A-GFP and HIV-1-G89V-GFP were unable to infect human PBMCs or CD4+ T cells (Figures 4A and S5). 2020 Cell reports Result HIV G89V;P90A 39;20 43;24 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. We found that TRIM5alphahu did not interact with mutant HIV-1 cores bearing the capsid change A92E (Figure 3C). 2020 Cell reports Result HIV A92E 94 98 Capsid 80 86 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. We observed similar results using the capsid mutant G94D (Figure 3C), which showed a similar pattern of infectivity when compared to HIV-1-A92E-GFP viruses. 2020 Cell reports Result HIV G94D;A92E 52;139 56;143 Capsid 38 44 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. We tested whether HIV-1-P90A-GFP infection was inhibited in TRIM5alphahu KD Jurkat cells. 2020 Cell reports Result HIV P90A 24 28 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. False-positive occurred at M184V (n = 2/59) and G190A (n = 3/59); all these false-positives by OLA-Simple were 100% wild-type by MiSeq. 2020 AIDS (London, England) Result HIV G190A;M184V 48;27 53;32 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. Of the four false-negative results, three were K103N/S (at 10.5, 11.9, and 22.4% mutant frequency) and one at G190A (at 20.59% mutant frequency). 2020 AIDS (London, England) Result HIV G190A;K103N;K103S 110;47;47 115;54;54 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. OLA-Simple genotyping was indeterminate (IND) for 2.7% (8/295) of all codons tested (Table 1), with 8.5% (5/59) at K65R, 3.4% (2/59) at Y181C, and 1.7% (1/59) at G190A. 2020 AIDS (London, England) Result HIV G190A;K65R;Y181C 162;115;136 167;119;141 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. There were no IND results at K103N/S and M184V. 2020 AIDS (London, England) Result HIV K103N;K103S;M184V 29;29;41 36;36;46 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. For example, the following hydrogen bonding pairs are observed between nearby active-site residues (Asp30 and Thr31) and Thr74 of cantilever and Asn88 of 80 s loop for most of the frames: Asp30(A)-Thr74(A), Asp30(B)-Thr74(B), Asp30(A)-Asn88(A), Asp30(B)-Asn88(B), Thr31(A)-Thr74(A), Thr31(B)-Thr74(B) in G40E; Asp30(A)-Thr74(A), Asp30(A)-Asn88(A), Thr31(A)-Thr74(A), Thr31(B)-Asn88(B) in G40R; Asp30(B)-Thr74(B), Thr31(B)-Thr74(B), Thr31(B)-Asn88(B) in Ab-bound; Asp30(A)-Thr74(A), Thr31(A)-Thr74(A), Asp30(B)-Thr74(B), Thr31(B)-Asn88(B) in RIT-bound. 2020 Scientific reports Result HIV G40E;G40R 304;388 308;392 Asp;Asp;Asp;Asp;Asp;Asp;Asp;Asp;Asp;Asp 100;188;207;226;245;310;329;394;463;501 103;191;210;229;248;313;332;397;466;504 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. In all the cases, the fluctuations in active-site are considerably reduced (except in chain B of G40E). 2020 Scientific reports Result HIV G40E 97 101 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. In G40E mutant and Ab bound protease, the mean distances between these two residue pairs His69(A)-Phe99(B) and His69(B)-Phe99(A) are about 1.2 +- 0.1 nm. 2020 Scientific reports Result HIV G40E 3 7 PR 28 36 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. In G40R and RIT-bound protease the mean distance between residue pair His69(A)-Phe99(B) is 1.2 +- 0.1 nm and His69(B)-Phe99(A) is about 0.8 +- 0.1 nm. 2020 Scientific reports Result HIV G40R 3 7 PR 22 30 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. In mutants, some new hydrogen-bonds are also formed between flaps and remaining parts of the protease such as Gln58(A)-Thr74(A), Gly51(A)-Pro79(B) in G40R and Gln58(B)-Thr74(B), Pro79(A)-Gly51(B) and Gly51(A)-Pro79(B) in G40E. 2020 Scientific reports Result HIV G40E;G40R 221;150 225;154 PR 93 101 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Mutations at position 40 have resulted in the formation of the salt-bridges between the residues Glu40 and Arg41 in G40E; Arg40 and Asp60 in G40R in both the monomers of the protease as shown in Figs. 2020 Scientific reports Result HIV G40E;G40R 116;141 120;145 PR;Asp 174;132 182;135 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. New hydrogen-bonds are observed in flaps of Ab/RIT bound protease and mutant proteases (G40E and G40R) as shown in Figs. 2020 Scientific reports Result HIV G40E;G40R 88;97 93;101 PR;PR 57;77 65;86 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Similarly, in RIT-bound and mutant proteases (G40E and G40R) also, the structure of protease is stable and the flaps remain in the closed conformation throughout the simulation, as shown in. 2020 Scientific reports Result HIV G40E;G40R 46;55 51;59 PR;PR 35;84 44;92 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The average number of hydrogen-bonds obtained from the distribution of hydrogen-bonds from the mutants (G40R = 134 +- 6, G40E = 139 +- 7), and Ab-bound (132 +- 5) is larger than that of WT-free protease (128 +- 6), even though the width of the distributions for both WT and mutants are similar (the standard deviations obtained from the variances are 6, 7 and 5). 2020 Scientific reports Result HIV G40E;G40R 121;104 125;109 PR 194 202 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The hydrogen-bonding interactions formed within the dimer-interface residues are: Cys95-Leu90, Gly94-Thr91, Gln7-Thr4 in chain A and Cys95-Leu90, Gly94-Leu90, Gly94-Thr91, Gln7-Thr4 in chain B of both the mutants; the hydrogen-bonding interactions between dimer-interface residues and residues belonging to 80 s loop/cantilever are: Gln92-Asn88, Gln92-Ile72 in chain A and Ile93-Leu89 in chain B of both the mutants; the interchain interactions formed by the dimer-interface residues are Thr96(A)-Gln2(B), Asn98(A)-Asn98(B), Thr96(A)-Asn98(B) in G40E and Gln2(A)-Thr96(B) Asn98(A)-Asn98(B) and Asn98(A)-Thr96(B) in G40R. 2020 Scientific reports Result HIV G40E;G40R 546;615 550;619 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The mean RMSD values of the WT-free protease, Ab-bound protease, RIT-bound protease, G40R and G40E mutants of HIV-1 proteases are (0.66 +- 0.07 nm), (0.33 +- 0.02 nm), (0.32 +- 0.03 nm), (0.30 +- 0.02 nm) and (0.26 +- 0.02 nm) respectively. 2020 Scientific reports Result HIV G40E;G40R 94;85 98;89 PR;PR;PR;PR 36;55;75;116 44;63;83;125 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The root means square fluctuations (RMSF) for the Calpha atoms of both the chains of WT-free, RIT-bound, Ab-bound and mutated proteases (G40E and G40R) are computed with respect to the representative structure from the simulation and are compared as shown in. 2020 Scientific reports Result HIV G40E;G40R 137;146 142;150 PR 126 135 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Thus fluctuations in the elbow region of chain A of Ab-bound protease are reduced more significantly as compared to the mutants G40E and G40R. 2020 Scientific reports Result HIV G40E;G40R 128;137 132;141 PR 61 69 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. We calculated and compared the Calpha-Calpha distance (flap tip distance) between the Ile-50 residues present at the tip of the flaps of the HIV-1 protease monomers (50Calpha(Ile)chainA-50'Calpha(Ile)chainB), in the WT-free, Ab-bound, RIT-bound and mutant (G40R and G40E) protease simulations. 2020 Scientific reports Result HIV G40E;G40R 266;257 270;262 PR;PR 147;272 155;280 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. We have examined the intra protein hydrogen-bonding and salt-bridge network in WT-free, Ab-bound, RIT-bound and mutant proteases (G40E and G40R) simulations to understand the changes in flexibility of protease upon mutation or RIT/Ab binding. 2020 Scientific reports Result HIV G40E;G40R 130;139 135;143 PR;PR 119;201 128;209 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. As shown in Figure 5A-C, B4 efficiently occupied the pockets of the single amino acid mutations K103N and E138K and the double mutants F227L + V106A with an approximately "U" conformation, which was one of the essential condition for the antiviral activity in the DAPY scaffold. 2020 Molecules (Basel, Switzerland) Result HIV E138K;F227L;K103N;V106A 106;135;96;143 111;140;101;148 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. Compound B6 exhibited the highest potency against the double mutant F227L + V106A among all target compounds with EC50 values of 1.52 muM. 2020 Molecules (Basel, Switzerland) Result HIV F227L;V106A 68;76 73;81 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. Docking of B4 with K103N + Y181C predicted that several common features ("U" binding conformation, hydrogen bonds, and pi-pi stacking interactions) would be lost, which might contribute to the decrease in antiviral activity of compound B4 against the HIV-1 double mutants K103N + Y181C. 2020 Molecules (Basel, Switzerland) Result HIV K103N;K103N;Y181C;Y181C 19;272;27;280 24;277;32;285 PI;PI 119;122 121;124 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. Furthermore, compounds B3-B6 were superior to NVP (EC50 = 4.28 muM) toward the virus with double mutations F227L + V106A. 2020 Molecules (Basel, Switzerland) Result HIV F227L;V106A 107;115 112;120 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. However, toward the virus with double mutations K103N + Y181C, all target compounds exhibited low activity. 2020 Molecules (Basel, Switzerland) Result HIV K103N;Y181C 48;56 53;61 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. The F227L decreased the pi-pi stacking interaction with the p-CN-phenyl ring leading to lower activity compared to those of Etravirine and Rilpivirine. 2020 Molecules (Basel, Switzerland) Result HIV F227L 4 9 PI;PI 24;27 26;29 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. They were inferior to the references EFV and ETR against the L100I and Y181C mutant strains. 2020 Molecules (Basel, Switzerland) Result HIV L100I;Y181C 61;71 66;76 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. Toward the E138K mutant, compounds B3 (EC50 = 0.14 muM) and B4 (EC50 = 0.11 muM) were more potent than NVP (EC50 = 0.20 muM). 2020 Molecules (Basel, Switzerland) Result HIV E138K 11 16 32235557 Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs. Toward the K103N mutant, compound B6 had an EC50 of 0.06 muM, which was more potent than the reference standards NVP (EC50 =4.70 muM) and EFV (EC50 = 0.08 muM). 2020 Molecules (Basel, Switzerland) Result HIV K103N 11 16 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. A patient receiving AZT, 3TC, EFV, d4T and LPV/r had a virus sequence with the T66I mutation (Table 1). 2020 Frontiers in microbiology Result HIV T66I 79 83 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. D67N occurred in five (5%) patients receiving AZT plus 3TC and in three (3%) patients receiving ABC plus 3TC. 2020 Frontiers in microbiology Result HIV D67N 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. D67N occurred in one (1%) patient receiving both TDF plus 3TC and an FTC plus TDF-based regimen. 2020 Frontiers in microbiology Result HIV D67N 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. E138QGA occurred in four (4%) patients receiving AZT plus 3TC, in three (3%) patients receiving ABC plus 3TC, and in one (1%) patient receiving TDF plus 3TC. 2020 Frontiers in microbiology Result HIV E138A;E138G;E138Q 0;0;0 7;7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. G190G/A occurred in six (6%) patients receiving AZT plus 3TC, and in three (3%) patients receiving ABC plus 3TC. 2020 Frontiers in microbiology Result HIV G190A;G190G 0;0 7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. H221Y and M230L occurred in one (1%) patient each; both these patients were receiving AZT plus 3TC. 2020 Frontiers in microbiology Result HIV M230L;H221Y 10;0 15;5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. However, Y115F occurred more often in patients receiving AZT plus 3TC (n = 4; 4%); it occured in one (1%) patient receiving ABC plus 3TC. 2020 Frontiers in microbiology Result HIV Y115F 9 14 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. K101EP occurred in three (3%) patients receiving AZT plus 3TC, and in one (1%) patient receiving ABC plus 3TC. 2020 Frontiers in microbiology Result HIV K101E;K101P 0;0 6;6 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. L74V was detected in five (5%) patients - three (3%) patients receiving ABC plus 3TC, and two (2%) patients receiving AZT plus 3TC. 2020 Frontiers in microbiology Result HIV L74V 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M184V/I was also found in two (4%) patients receiving TDF plus 3TC, compared with those receiving FTC plus TDF (n = 1; 2%). 2020 Frontiers in microbiology Result HIV M184I;M184V 0;0 7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M184V/I was detected in 52 (54%) patients suspected of failing cART. 2020 Frontiers in microbiology Result HIV M184I;M184V 0;0 7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. P225H occurred in 10 (10%) patients receiving AZT plus 3TC, in three (3%) patients receiving ABC plus 3TC, and in two (2%) patients receiving TDF plus 3TC. 2020 Frontiers in microbiology Result HIV P225H 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. T215Y occurred in two (2%) patients receiving AZT plus 3TC. 2020 Frontiers in microbiology Result HIV T215Y 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The A62V mutation occurred in one (1%) patient receiving AZT plus 3TC. 2020 Frontiers in microbiology Result HIV A62V 4 8 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The K219E/Q mutation occurred in six (6%) patients receiving AZT plus 3TC, and in two (2%) patients receiving FTC plus TDF. 2020 Frontiers in microbiology Result HIV K219E;K219Q 4;4 11;11 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The K65R/N mutation occurred in five (5%) patients; K65R occurred in two (2%) patients receiving AZT plus 3TC, and in one (1%) patient receiving TDF plus FTC. 2020 Frontiers in microbiology Result HIV K65N;K65R;K65R 4;4;52 10;10;56 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The M41L mutation occurred in three (3%) patients receiving AZT plus 3TC, and in one (1%) patient receiving 3TC plus ATV/r. 2020 Frontiers in microbiology Result HIV M41L 4 8 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The most common major PI RAMs observed were M46I and V82A (n = 12; 12%); I54V (n = 10; 10%); I84V and L76V (n = 7; 7%); I47A/V (n = 3; 3%); I50L/V (n = 2; 2%); and V32I (n = 2; 2%) (Table 1). 2020 Frontiers in microbiology Result HIV I47A;I47V;I50L;I50V;I54V;I84V;L76V;M46I;V32I;V82A 120;120;140;140;73;93;102;44;164;53 126;126;146;146;77;97;106;48;168;57 PI 22 24 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The most frequent TAMs observed were K70R/E in 10 (10%) patients receiving AZT plus 3TC, in three (3%) patients receiving ABC plus 3TC, and in one (1%) patient receiving FTC plus TDF. 2020 Frontiers in microbiology Result HIV K70E;K70R 37;37 43;43 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The mutation identified and classified as an 'accessory' integrase, E157Q, occurred in two (2%) patients. 2020 Frontiers in microbiology Result HIV E157Q 68 73 IN 57 66 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The Y115F mutation occurred in five (5%) patients. 2020 Frontiers in microbiology Result HIV Y115F 4 9 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Two (2%) patient had a viral sequences with Y143R major InSTI mutation in combination with the accessory T97A mutation, which confers high-level resistance to raltegravir (RAL), intermediate resistance to elvitegravir (EVG), and potential low-level resistance to bictegravir and dolutegravir (DTG). 2020 Frontiers in microbiology Result HIV T97A;Y143R 105;44 109;49 INSTI 56 61 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. V106M occurred in 10 (10%) patients receiving AZT plus 3TC, and in two (2%) patients receiving ABC plus 3TC. 2020 Frontiers in microbiology Result HIV V106M 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. V108I occurred in one (1%) patient receiving AZT plus 3TC. 2020 Frontiers in microbiology Result HIV V108I 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. V75I occurred in one (1%) patient receiving AZT plus 3TC. 2020 Frontiers in microbiology Result HIV V75I 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. We observed M184V/I as the most prevalent NRTI mutation. 2020 Frontiers in microbiology Result HIV M184I;M184V 12;12 19;19 NRTI 42 46 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. We observed that the K103N/S mutation occurred in 41 (43%) of those patients failing cART. 2020 Frontiers in microbiology Result HIV K103N;K103S 21;21 28;28 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Y188L occurred in five (5%) patients receiving AZT plus 3TC, and in two (2%) patients receiving TDF plus ATV/r, and in one (1%) patient receiving ABC plus 3TC. 2020 Frontiers in microbiology Result HIV Y188L 0 5 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Also R57K/G occurred in 83.3% (10/12) of subtypes G/UG and 12.5% (2/16) of CRF02_AG. 2020 PloS one Result HIV R57G;R57K 5;5 11;11 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Furthermore, a polymorphism at a known primary mutation site (V82I) was found in all subtype G/UG samples. 2020 PloS one Result HIV V82I 62 66 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. It is important to note that C67E/S, V82I and E35Q mutations were found only among the G/UG isolates. 2020 PloS one Result HIV C67E;C67S;E35Q;V82I 29;29;46;37 35;35;50;41 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Major drug resistance mutations were identified at two protease sites (M46L and V82L) previously characterized for drug resistance in three of the sequences (Table 1). 2020 PloS one Result HIV M46L;V82L 71;80 76;84 PR 55 63 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Major mutation that confers resistance to protease inhibitors, M46L was found in two out of the twelve (16.7%) subtypes G/ UG sequences while V82L, was present in one out of the sixteen (6.3%) CRF02_AG sequences. 2020 PloS one Result HIV M46L;V82L 63;142 67;146 PR 42 50 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Minor PI mutations detected among the isolates include; L10I/V [7/28 (25.0%)], K20I [28/28 (100%)], L33F [1/28 (3.6%)] and N88D [1/28 (3.6%)]. 2020 PloS one Result HIV K20I;L10I;L10V;L33F;N88D 79;56;56;100;123 83;62;62;104;127 PI 6 8 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Other common mutations at positions not selected for drug resistance include; I13V/A which occurred in all the samples; C67E/S found in all subtypes G/UG; E35Q occurred in 91.7% of subtypes G/UG; N37D/S/E/H which occurred in 41.7% and 25.0% of subtypes G/UG and CRF02_AG respectively. 2020 PloS one Result HIV C67E;C67S;E35Q;I13A;I13V;N37D;N37E;N37H;N37S 120;120;155;78;78;196;196;196;196 126;126;159;84;84;206;206;206;206 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Polymorphisms at known secondary mutation sites (K20I, M36I/L, H69K/R and L89M) were found in all the samples while L63T/P/S/Q was found in 83.3% (10/12) and 31.3% (5/16) of subtypes G/UG and CRF02_AG respectively. 2020 PloS one Result HIV H69K;H69R;K20I;L63P;L63Q;L63S;L63T;L89M;M36I;M36L 63;63;49;116;116;116;116;74;55;55 69;69;53;126;126;126;126;78;61;61 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Reduced HIV-1 susceptibility was predicted for the only non-boosted Nelfinavir in all (100%) of the sequences due to general presence of K20I. 2020 PloS one Result HIV K20I 137 141 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. 14 NRTI-associated DRMs were all found in CRF01_AE, and V75I/L/M, T69N/D, and L210W were not found in CRF07_BC (S ). 2020 BioMed research international Result HIV L210W;T69D;T69N;V75I;V75L;V75M 78;66;66;56;56;56 83;72;72;64;64;64 NRTI 3 7 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. 16 and 15 (except A98G) NNRTI-associated DRMs were found in CRF01_AE and CRF07_BC, respectively. 2020 BioMed research international Result HIV A98G 18 22 NNRTI 24 29 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. E138A/G/R/K/Q was found in this case and was predicted to have low/potential resistance to RPV and ETR. 2020 BioMed research international Result HIV E138A;E138G;E138K;E138Q;E138R 0;0;0;0;0 13;13;13;13;13 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. K103N (37.55%, 92/245) was the most frequent mutation, followed by G190A/E/K/Q/S/V (28.57%, 70/245), V179I/D/E/T (27.76%, 68/245), V106A/I/M (26.12%, 64/245), Y181C/V (18.78%, 46/245), K101E/H/P (14.69%, 36/245), Y188C/H/L (5.71%, 14/245), L100I (4.08%, 10/245), and M230L (4.08%, 10/245). 2020 BioMed research international Result HIV G190A;G190E;G190K;G190Q;G190S;G190V;K101E;K101H;K101P;L100I;M230L;V106A;V106I;V106M;V179D;V179E;V179I;V179T;Y181C;Y181V;Y188C;Y188H;Y188L;K103N 67;67;67;67;67;67;185;185;185;240;267;131;131;131;101;101;101;101;159;159;213;213;213;0 82;82;82;82;82;82;194;194;194;245;272;140;140;140;112;112;112;112;166;166;222;222;222;5 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. NNRTI-associated DRMs with extensively drug resistance such as G190A/E/K/Q/S/V, V179I/D/E/T, Y181C/V, and K101E/H/P reside in CRF55_01B and subtype B, C. 2020 BioMed research international Result HIV G190A;G190E;G190K;G190Q;G190S;G190V;K101E;K101H;K101P;V179D;V179E;V179I;V179T;Y181C;Y181V 63;63;63;63;63;63;106;106;106;80;80;80;80;93;93 78;78;78;78;78;78;115;115;115;91;91;91;91;100;100 NNRTI 0 5 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. One patient infected with CRF07_BC recombinant subtype showed M46I, I47A, and I50V 3 primary mutations, which was predicted to be resistant to all PIs. 2020 BioMed research international Result HIV I47A;I50V;M46I 68;78;62 72;82;66 PI 147 150 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. The most commonly observed mutations with NRTIs were M184I/V (59.59%, 146/245), K65R (28.16%, 69/245), D67N/G (19.18%, 47/245), K70E/K/R (17.14%, 42/245), Y115F (15.10%, 37/245), L74I/V (11.02%, 27/245), and T215I/Y (8.16%, 20/245). 2020 BioMed research international Result HIV D67G;D67N;K65R;K70E;K70K;K70R;L74I;L74V;M184I;M184V;T215I;T215Y;Y115F 103;103;80;128;128;128;179;179;53;53;208;208;155 109;109;84;136;136;136;185;185;60;60;215;215;160 NRTI 42 47 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. The most frequent mutations were L10I/V (32), A71I/T/V (28), and K20I/R (26), among which L10I/V and A71I/T/V are mutations that do not affect drug susceptibility and K20I/R were predicted to have potential resistance to NFV. 2020 BioMed research international Result HIV A71I;A71I;A71T;A71T;A71V;A71V;K20I;K20I;K20R;K20R;L10I;L10I;L10V;L10V 46;101;46;101;46;101;65;167;65;167;33;90;33;90 54;109;54;109;54;109;71;173;71;173;39;96;39;96 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. As shown in Fig 2, infection with the N74D CA mutant can be rescued by TRIM34 knockout in CD4+ T cells (Fig 3B). 2020 PLoS pathogens Result HIV N74D 38 42 Capsid 43 45 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Cell pellets and viral supernatants were collected and both genomic DNA from cells and viral RNA from virions were isolated and amplified for deep sequencing and MAGeCK analysis to identify sgRNA sequences significantly enriched in the viral supernatant of each virus (Fig 1B: WT vs P90A; Fig 1C: WT vs N74D; see S1 Table for full screen results). 2020 PLoS pathogens Result HIV N74D;P90A 303;283 307;287 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Consistent with the results of our initial screen with P90A (Fig 1B) and with other recently published results on TRIM5alpha-sensitivity of this virus, we find that P90A is more sensitive to TRIM5alpha restriction than HIV-1 WT (Fig 4C: CD4+ T Cells; Fig 4F: MoDCs). 2020 PLoS pathogens Result HIV P90A;P90A 55;165 59;169 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Control and TRIM34-KO cell populations were then infected with both WT and N74D viruses after overnight IFN treatment and the % infected cells was assayed by flow cytometry. 2020 PLoS pathogens Result HIV N74D 75 79 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Finally, we asked if TRIM5alpha restriction of the CypA-binding deficient P90A capsid mutant virus depends on TRIM34. 2020 PLoS pathogens Result HIV P90A 74 78 Capsid 79 85 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. For the N74D screen, we find a novel HIV-1 restriction factor gene, TRIM34, as the highest-scoring hit that is not found in the screen with WT HIV-1 (Fig 1C: Green). 2020 PLoS pathogens Result HIV N74D 8 12 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Given that TRIM34, together with TRIM5alpha, restricts N74D capsids but not WT capsids, we hypothesized that this differential restriction could be due to the localization of TRIM34 and TRIM5alpha to N74D capsids that does not occur, or does not occur to the same extent, as with WT capsids. 2020 PLoS pathogens Result HIV N74D;N74D 55;200 59;204 Capsid;Capsid;Capsid;Capsid 60;79;205;283 67;86;212;290 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. However, knockout of TRIM34 in primary CD4+ T cells has an 8-fold effect which is an even stronger effect on N74D than what we observed in THP-1 cells (Fig 2D; P<0.01, compare with Fig 2A). 2020 PLoS pathogens Result HIV N74D 109 113 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. However, this restriction activity is independent of TRIM34 as TRIM34 knockout or knockdown has little to no effect on P90A (Fig 4C: CD4+ T Cells; Fig 4F: MoDCs). 2020 PLoS pathogens Result HIV P90A 119 123 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Importantly, while we initially identified TRIM34 in a screen for IFN-induced genes that block the N74D virus, these data suggest that TRIM34 is actually a constitutive block to infection whose activity is IFN-independent. 2020 PLoS pathogens Result HIV N74D 99 103 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In both capsid mutant screens we measured a lower rank for MXB than for WT (Fig 1B and 1C-compare rank in WT screen as compared to either capsid mutant), consistent with the previously-reported relative resistance of both P90A and N74D to restriction by MXB. 2020 PLoS pathogens Result HIV N74D;P90A 231;222 235;226 Capsid;Capsid 8;138 14;144 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In contrast to the restriction of the N74D capsid mutant virus measured in TRIM34-overexpressing cells, we do not observe any restriction of the N57A capsid mutant (Fig 3C). 2020 PLoS pathogens Result HIV N57A;N74D 145;38 149;42 Capsid;Capsid 43;150 49;156 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In contrast, TRIM5 is the highest-scoring gene hit for P90A (Fig 1B: yellow). 2020 PLoS pathogens Result HIV P90A 55 59 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In contrast, we observe 2.2-fold rescue of N74D replication across both TRIM34 KO pools (Fig 2A; P<0.001), consistent with our HIV-CRISPR screen results that found TRIM34 as a block to N74D infection in THP-1 cells. 2020 PLoS pathogens Result HIV N74D;N74D 43;185 47;189 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In contrast, we observe significant inhibition of the N74D mutant by TRIM34 (Fig 2E, right panel). 2020 PLoS pathogens Result HIV N74D 54 58 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In order to test this hypothesis, we stably-overexpressed human TRIM34 in clonal TRIM34-KO THP-1 cells and assayed replication of both the wild type and the N74D CA mutant viruses. 2020 PLoS pathogens Result HIV N74D 157 161 Capsid 162 164 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In the HIV-CRISPR screens described here, a library of cells transduced with the HIV-CRISPR vector targeting genes enriched in ISGs, the PIKAHIV library, was infected with WT, N74D or P90A viruses after overnight treatment with IFN alpha. 2020 PLoS pathogens Result HIV N74D;P90A 176;184 180;188 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Indeed, consistent with a requirement of TRIM5alpha for the TRIM34-medicated restriction, we find that knockout of either TRIM34 or TRIM5alpha is sufficient to rescue infection with the N74D capsid mutant (Fig 4C) while neither knockout has a significant effect on WT HIV-1 infection (Fig 4C). 2020 PLoS pathogens Result HIV N74D 186 190 Capsid 191 197 HIV infections 268 283 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Moreover, there is a block prior to reverse transcription of the N74D CPSF6-binding capsid mutant in macrophages. 2020 PLoS pathogens Result HIV N74D 65 69 RT;Capsid 36;84 57;90 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Next, a core set of ISGs, including MXB (MX2), IFITM1, TETHERIN (BST2) and TRIM5, were some of the highest-scoring gene hits for all three viruses screened (WT, N74D and P90A viruses). 2020 PLoS pathogens Result HIV N74D;P90A 161;170 165;174 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. P90A and N74D have been shown to be impaired in replication both in IFN-treated and untreated cells. 2020 PLoS pathogens Result HIV N74D;P90A 9;0 13;4 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Quantification of the number of p24gag+ puncta that are also positive for TRIM34 and TRIM5alpha shows that colocalization of both TRIM proteins with p24gag occurred more frequently for N74D capsids than for WT capsids (Fig 5B). 2020 PLoS pathogens Result HIV N74D 185 189 Capsid;Capsid 190;210 197;217 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. The N74D CA mutant virus was first characterized due to its loss of CPSF6 binding. 2020 PLoS pathogens Result HIV N74D 4 8 Capsid 9 11 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Therefore, TRIM34 and TRIM5alpha are present together with incoming N74D HIV-1 capsids in the cytoplasm of infected cells. 2020 PLoS pathogens Result HIV N74D 68 72 Capsid 79 86 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Therefore, we hypothesized that the P90A (CypA-deficient) and N74D (CPSF6-deficient) capsid mutants may be more sensitive to inhibition by capsid-targeting restriction factors in human cells. 2020 PLoS pathogens Result HIV N74D;P90A 62;36 66;40 Capsid;Capsid 85;139 91;145 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. To ask if this requirement of TRIM5alpha for TRIM34-mediated restriction is also important in primary cells, we knocked out either TRIM34 or TRIM5 in primary CD4+ cells and infected each cell pool with WT, N74D or P90A in comparison to a control cell pool (Fig 4C; TRIM34-KO 69% ICE KO-score, TRIM5-KO 87% ICE KO-score). 2020 PLoS pathogens Result HIV N74D;P90A 206;214 210;218 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. To ask if TRIM34 restriction occurs only in IFN-treated cells as has recently been shown for TRIM5alpha, we also infected control and TRIM34-KO cells with WT and N74D virus without any IFN treatment and assayed the % infected cells by flow cytometry (Fig 2B). 2020 PLoS pathogens Result HIV N74D 162 166 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. To further explore the CPSF6-independence of TRIM34 restriction, we also assayed replication of another CPSF6-binding deficient mutant, N57A, in our ectopic overexpression system. 2020 PLoS pathogens Result HIV N57A 136 140 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. To test this hypothesis, HA-TRIM34 and YFP-TRIM5alpha stably-expressing HeLa cells were infected with WT or the N74D viruses and 2 hours later colocalization of both TRIM34 and TRIM5alpha with each capsid was measured. 2020 PLoS pathogens Result HIV N74D 112 116 Capsid 198 204 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. To validate the screen results (Fig 1) which suggest that TRIM34 restricts N74D but not WT HIV-1, we knocked out TRIM34 in THP-1 cells by transduction with a lentiviral vector encoding Cas9 and two different TRIM34-specific sgRNAs together with Non-Targeting Control (NTC) sgRNAs (Fig 2A and 2B). 2020 PLoS pathogens Result HIV N74D 75 79 Capsid 185 187 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. TRIM34 and TRIM5alpha complexes colocalize with N74D capsids. 2020 PLoS pathogens Result HIV N74D 48 52 Capsid 53 60 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. TRIM34 inhibits N74D at a step before completion of reverse transcription. 2020 PLoS pathogens Result HIV N74D 16 20 RT 52 73 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. TRIM34 scores as highly as the IFN pathway genes (Fig 1C: Magenta), highlighting the key role TRIM34 potentially plays in blocking replication of the N74D capsid mutant virus. 2020 PLoS pathogens Result HIV N74D 150 154 Capsid 155 161 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Unlike TRIM5alpha inhibition of wild type HIV-1 capsids, TRIM34 is a constitutive inhibitor of the N74D CA mutant as KO rescues infection of the N74D virus even in the absence of IFN treatment 2.0-Fold (Fig 2B; P<0.001). 2020 PLoS pathogens Result HIV N74D;N74D 99;145 103;149 Capsid;Capsid 48;104 55;106 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. We also find TRIM34 as a less significant hit in the P90A screen as compared to the N74D screen, suggesting it may have a minor role in restriction of the P90A virus at least in some cell types (Fig 1B). 2020 PLoS pathogens Result HIV N74D;P90A;P90A 84;53;155 88;57;159 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. We infected the control and TRIM34-KO pools with both WT and N74D viruses and measured infection levels after 2 days by flow cytometry. 2020 PLoS pathogens Result HIV N74D 61 65 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. We observe colocalization of TRIM34 and TRIM5alpha together with both WT and N74D HIV-1 capsids in the cell cytoplasm (Fig 5A-WT and N74D; white arrowheads are puncta with p24gag, TRIM34 and TRIM5alpha). 2020 PLoS pathogens Result HIV N74D;N74D 77;133 81;137 Capsid 88 95 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. While there is little effect of mac TRIM34 overexpression on wild type HIV-1 (Fig 3F), we observe significant restriction of the N74D HIV-1 virus (Fig 3G). 2020 PLoS pathogens Result HIV N74D 129 133 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. However, vdW interactions between the V32I and I47V mutations cause flap closure in HIV-1 PR (Figure 3). 2014 Discoveries (Craiova, Romania) Result HIV I47V;V32I 47;38 51;42 PR 90 92 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. I47V likely contributes to flap opening as it is present in both isolates 1 and 2 where the flaps open but not in DetMDR3 where the flaps do not open. 2014 Discoveries (Craiova, Romania) Result HIV I47V 0 4 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. I54M and L90M are associated with asymmetric movement in DetMDR1 corresponding to opening of the flaps. 2014 Discoveries (Craiova, Romania) Result HIV L90M;I54M 9;0 13;4 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. I54M in combination with L90M plays a role in asymmetric flap movement. 2014 Discoveries (Craiova, Romania) Result HIV L90M;I54M 25;0 29;4 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. The RMSD of L90M on chain B is different than that of chain A. 2014 Discoveries (Craiova, Romania) Result HIV L90M 12 16 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. These vdW interactions could explain the flap opening followed by quick flap closure observed in DetMDR1, while the absence of V32I in DetMDR2 removes this interaction and cause the flaps to remain open. 2014 Discoveries (Craiova, Romania) Result HIV V32I 127 131 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. V32I interacts with I47V to tether the protease flaps in a closed conformation. 2014 Discoveries (Craiova, Romania) Result HIV I47V;V32I 20;0 24;4 PR 39 47 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. A62VPR was detected in 60/191 (31.4%) of the A6 sequences. 2020 Viruses Result HIV A62V 0 6 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. Conversely, A62VPR and G190SPR correlated with A6 infections. 2020 Viruses Result HIV A62V;G190S 12;23 18;30 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. Moreover, G190SPR was observed in 16/30 (53.3%) of the efavirenz (EFV)-exposed patients, resulting in a significant association of this RAM in the context of A6 and EFV-exposure (p < 0.001). 2020 Viruses Result HIV G190S 10 17 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. On the other hand, G190SPR was not detected in any TN patient but in 14/75 (18.7%) of the TE patients. 2020 Viruses Result HIV G190S 19 26 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. RAMs I54AVPR, L90MPR, M41LRT, D67NPR, and T215FPR were significantly more frequent in subtype G isolates. 2020 Viruses Result HIV D67N;I54A;I54V;L90M;M41L;T215F 30;5;5;14;22;42 36;12;12;20;28;49 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. 3, none of Yunnan sequences harbored the K103R/V179D mutation, regardless of the risk group. 2020 BMC infectious diseases Result HIV K103R;V179D 41;47 46;52 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. A single T-to-A transversion at the third position of codon 179 in CRF65_cpx may be responsible for the emergence of V179E mutation in one patient. 2020 BMC infectious diseases Result HIV V179E 117 122 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. All V179D mutations were encoded by codon GAT, whereas the V179E mutation was encoded by codon GAA. 2020 BMC infectious diseases Result HIV V179D;V179E 4;59 9;64 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. However, the effects of combinations of K103R plus V179E and E138A plus V179D on NNRTI susceptibility are still not clear, which suggested that these two mutation patterns deserve further investigation. 2020 BMC infectious diseases Result HIV E138A;K103R;V179D;V179E 61;40;72;51 66;45;77;56 NNRTI 81 86 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. In addition, V179D mutation was accompanied by E138A mutation in one patient, and these two mutations resulted in low-level resistance to ETR and RPV. 2020 BMC infectious diseases Result HIV E138A;V179D 47;13 52;18 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Moreover, sequences harboring K103R/V179D mutation accounted for more than half (58.3%, 7/12) of all cluster III sequences, demonstrating the natural presence of the K103R/V179D mutation in this larger MSM cluster. 2020 BMC infectious diseases Result HIV K103R;K103R;V179D;V179D 30;166;36;172 35;171;41;177 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Natural presence of the V179D and K103R/V179D mutations in CRF65_cpx strains. 2020 BMC infectious diseases Result HIV K103R;V179D;V179D 34;24;40 39;29;45 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Obviously, V179D mutation was a signature mutation in CRF65_cpx patients due to a strong founder effect. 2020 BMC infectious diseases Result HIV V179D 11 16 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Of note, all seven CRF65_cpx sequences harboring K103R/V179D mutation were exclusively present in MSM cluster III. 2020 BMC infectious diseases Result HIV K103R;V179D 49;55 54;60 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Surprisingly, the combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive patients, also indicating the natural presence of K103R/V179D in CRF65_cpx strains (Table 1). 2020 BMC infectious diseases Result HIV K103R;K103R;V179D;V179D 43;189;33;195 48;194;38;200 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. V179D occurred alone in 22 patients, accounting for nearly 70% of all patients with CRF65_cpx. 2020 BMC infectious diseases Result HIV V179D 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. V179D, Y181C, and H221Y were detected in the one treatment-experienced patient. 2020 BMC infectious diseases Result HIV H221Y;Y181C;V179D 18;7;0 23;12;5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. We also found that two polymorphic accessory mutations, K103R and V179E, occurred simultaneously in one patient. 2020 BMC infectious diseases Result HIV K103R;V179E 56;66 61;71 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. We next sought to investigate the distribution of the K103R/V179D mutation in different risk groups and geographic areas. 2020 BMC infectious diseases Result HIV K103R;V179D 54;60 59;65 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. With respect to geographic distribution, K103R/V179D mutation was detected in four provinces: four patients from Beijing, one patient from Hebei, one patient from Jilin, and one patient from Anhui. 2020 BMC infectious diseases Result HIV K103R;V179D 41;47 46;52 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. With the exception of one patient who had NNRTI-resistance mutation V179E, the other 31 patients harbored V179D mutation, which resulted in the natural presence of V179D in CRF65_cpx strains (Table 1). 2020 BMC infectious diseases Result HIV V179D;V179D;V179E 106;164;68 111;169;73 NNRTI 42 47 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Importantly, we found that the V179T-carrying variants appeared in half (50%) of identified TCs. 2020 Infection and drug resistance Result HIV V179T 31 36 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. The most frequently observed SDRM was NNRTI mutation V179D/T, which appeared in 86 participants. 2020 Infection and drug resistance Result HIV V179D;V179T 53;53 60;60 NNRTI 38 43 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. The most frequently observed SDRMs were V179D/T (8.3%), E138A (4.1%) and L33F (2.4%), which are involved in the resistance to NNRTIs, NNRTIs, and PIs, respectively (Figures 2 and 3B). 2020 Infection and drug resistance Result HIV E138A;L33F;V179D;V179T 56;73;40;40 61;77;47;47 NNRTI;NNRTI;PI 126;134;146 132;140;149 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. There were four TCs involving V179T-carrying strains, and five TCs for L33F-, L90M-, A98G-, E138A- and T215TADN-carrying strains each. 2020 Infection and drug resistance Result HIV A98G;E138A;L33F;L90M;T215A;T215D;T215N;T215T;V179T 85;92;71;78;103;103;103;103;30 89;97;75;82;111;111;111;111;35 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Three TCs were formed by strains carrying two SDRMs, including L33F/V179T-carrying strains, A62V/V179T-carrying strains and A98G/Y181C-carrying strains (Figure 4). 2020 Infection and drug resistance Result HIV A62V;A98G;L33F;V179T;V179T;Y181C 92;124;63;68;97;129 96;128;67;73;102;134 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Two CRF01_AE strains in the TC 10 carried two SDRMs -A62V and V179T. 2020 Infection and drug resistance Result HIV A62V;V179T 53;62 57;67 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Two TCs (Clusters 3 and 8) contained three individuals who carried single SDRM E138A or A98G. 2020 Infection and drug resistance Result HIV A98G;E138A 88;79 92;84 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Furthermore, two blood donors with K103N mutation in the reverse transcriptase gene would be anticipated to have high-level resistance (HLR) to HIV-1 drug. 2020 Scientific reports Result HIV K103N 35 40 RT 57 78 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Most of the NNRTI DRMs (V179D/E [72.7%, 16/22]) were observed in HIV-1 infected blood donors and a combination of V179D and K103R were found in two samples may synergistically reduce ARV drug susceptibility. 2020 Scientific reports Result HIV K103R;V179D;V179D;V179E 124;24;114;24 129;32;119;32 NNRTI 12 17 HIV infections 65 79 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Most of the PI accessory DRMs were Q58E (3 out of 4) and all the HIV-1 isolates with Q58E mutations in our study were CRF07_BC strains. 2020 Scientific reports Result HIV Q58E;Q58E 35;85 39;89 PI 12 14 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. TDR analysis in PR and PR by Calibrated Population Resistance tool showed that 4 HIV-1 isolates (2.4%, 4/168) had surveillance drug-resistance mutation (SDRM), including 3 NNRTI SDRMs (1 K101E, 2 K103N) and 1 PI SDRM (M46I) (Table 3). 2020 Scientific reports Result HIV M46I 218 222 NNRTI;PI;PR;PR 172;209;16;23 177;211;18;25 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. The PI major DRMs included M46L, M46I and N88S. 2020 Scientific reports Result HIV M46I;M46L;N88S 33;27;42 37;31;46 PI 4 6 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Both the van der Waals and the electrostatic interaction energies contributed significantly to the total binding energy observed in the G140S mutant, while the polar solvation and SASA energy each had smaller contributions to the binding of the drug. 2020 PloS one Result HIV G140S 136 141 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Calculation of the covariance matrix values after diagonalization showed a significant increase for the G140S system (18.33 nm) compared to the other three systems WT, E92Q and Y143R each having 9.58 nm, 8.98 nm and 10.41 nm lower values, respectively. 2020 PloS one Result HIV E92Q;G140S;Y143R 168;104;177 172;109;182 Matrix 30 36 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Distance analysis indicated a smaller average distance of 0.21 +- 0.01 nm and 0.22 +- 0.01 nm between the WT, Y143R MG ion and drug DTG systems compared to E92Q and G140S each having a distance of 0.41 +- 0.04 nm, 0.99 +- 0.20 nm, respectively. 2020 PloS one Result HIV E92Q;G140S;Y143R 156;165;110 160;170;115 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. For the Y143R system the van der Waals, polar solvattion and SASA energy were the major contributors to the binding free energy, while the electrostatic interaction energy had no contribution. 2020 PloS one Result HIV Y143R 8 13 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Interestingly, no active site residue and MG ionic interactions were formed between DTG and the G140S mutant system, resulting in the dissociation of the drug from the binding pocket over time (S6D Fig). 2020 PloS one Result HIV G140S 96 101 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. On the other hand, the E92Q system showed interactions with one of the active site residues (D116) but no MG ionic interactions (Table 3). 2020 PloS one Result HIV E92Q 23 27 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Only G140S showed higher RMSD variation values compared to the WT, Y143R and E92Q systems (Fig 2A). 2020 PloS one Result HIV E92Q;G140S;Y143R 77;5;67 81;10;72 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. RMSF analysis clearly showed higher flexibility for the G140S mutant system, with four highly flexible regions (residues 68-70, 142-146, 166-170 and 253-256) compared to the WT, E92Q and Y143R systems (Fig 2B). 2020 PloS one Result HIV E92Q;G140S;Y143R 178;56;187 182;61;192 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Similarly, interactions were observed between the drug DTG and known active site residue D64, Y143R, N148, MG ion and DNA nucleotides for the Y143R system (Table 3). 2020 PloS one Result HIV Y143R;Y143R 94;142 99;147 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The 2D projections of the first and second principal components for the WT vs E92Q, WT vs Y143R and WT vs G140S systems are shown in S3A, S3B and S3C. 2020 PloS one Result HIV E92Q;G140S;Y143R 78;106;90 82;111;95 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The average number of hydrogen bonds formed between the protein-DNA-MG and drug were calculated to be 1.58, 0.34, 0.20 and 0.54 for the WT, E92Q, G140S and Y143R, respectively (S4A-S4D Fig). 2020 PloS one Result HIV E92Q;G140S;Y143R 140;146;156 144;151;161 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The FoldX change in unfolded energy values indicated that the G140S was stabilizing, E92Q destabilizing and Y143R neutral based on comparison with the WT structure each having values of 162.89, 131.94, 146.47 and 151.83 Kcal/Mol, respectively. 2020 PloS one Result HIV E92Q;G140S;Y143R 85;62;108 89;67;113 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The highest total binding free energy was observed for the WT (-29.65 +- 18.54 Kcal/Mol) followed by the Y143R mutant system (-23.20 +- 10.52 Kcal/Mol) and G140S mutant system (-21.93 +- 23.11 Kcal/Mol), while the E92Q mutant system showed the weakest binding free energy of (-20.65 +- 9.36 Kcal/Mol) (Table 2). 2020 PloS one Result HIV E92Q;G140S;Y143R 214;156;105 218;161;110 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The major contributors to the total binding free energy in the WT was the van der Waals energy, electrostatic interaction energy and SASA energy, while the polar solvation had no contribution (because of its positive value) to the binding of the drug and similarly for the E92Q mutant (Table 2). 2020 PloS one Result HIV E92Q 273 277 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The Radius of gyration values indicated decreasing values for Y143R and E92Q compared to the WT and G140S mutant system (Fig 2C). 2020 PloS one Result HIV E92Q;G140S;Y143R 72;100;62 76;105;67 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The RMSD showed equilibrium after 100 ns for the WT system while the G140S mutant system showed increasing RMSD values comparable to the first run (S5A Fig). 2020 PloS one Result HIV G140S 69 74 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. The total non-bonded pairwise interaction energies between the HIV-1C IN protein and DTG were found to be higher for the WT (-94.54 +- 13.20) compared to the three mutant structures (E92Q, Y143R and G140S) each having, -38.74 +- 6.70, -27.97 +- 2.37 and -16.49 +- 1.02 KJ/Mol, respectively. 2020 PloS one Result HIV E92Q;G140S;Y143R 183;199;189 187;204;194 IN 70 72 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Trajectory analysis of the RMSD of the backbone indicated that the WT system reached equilibrium after 100 ns as well as the E92Q, Y143R and G140S mutant systems (Fig 2A). 2020 PloS one Result HIV E92Q;G140S;Y143R 125;141;131 129;146;136 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Although E138 G and V179D/E independently confer potential low-level resistance to EFV/NVP, their combination (LC17S374 and LC17S467) resulted in low-level resistance to EFV/NVP (Supplementary Table S2). 2020 Epidemiology and infection Result HIV E138G;V179D;V179E 9;20;20 15;27;27 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Among the key DRMs for NNRTIs, Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322) conferred high-level resistance, K101E (0.9%, 3/322) and P225H (0.9%, 3/322) conferred intermediate resistance and H221Y (0.9%, 3/322) conferred low-level resistance. 2020 Epidemiology and infection Result HIV G190A;H221Y;K101E;K103N;P225H;Y188C;Y188F;Y188L 80;215;133;56;157;31;31;31 85;220;138;61;162;40;40;40 NNRTI 23 29 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Among the key DRMs for NRTIs, K65R (1.6%, 5/322) conferred high-level resistance, T69D (0.3%, 1/322) conferred intermediate resistance and M41L (0.6%, 2/322), D67N (0.6%, 2/322) and T215D (0.3%, 1/322) conferred low-level resistance. 2020 Epidemiology and infection Result HIV D67N;K65R;M41L;T215D;T69D 159;30;139;182;82 163;34;143;187;86 NRTI 23 28 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Among the key DRMs for PIs, I50 V (0.3%, 1/322) conferred intermediate resistance and I47 V (0.3%, 1/322) conferred low-level resistance. 2020 Epidemiology and infection Result HIV I47V;I50V 86;28 91;33 PI 23 26 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. The drug resistance-associated mutations are shown in Table 2, among which E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were far higher than the others. 2020 Epidemiology and infection Result HIV E138A;E138G;E138K;E138R;V179D;V179E;V179T 75;75;75;75;107;107;107 86;86;86;86;116;116;116 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. A single-residue change Q563R in gp41 of Env E1 is responsible for the increased infectivity in the presence of HIV-positive plasma. 2020 PLoS pathogens Result HIV Q563R 24 29 gp41;Env 33;41 37;44 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Anti-cluster I antibodies restore the Q563R-mediated infectivity defect. 2020 PLoS pathogens Result HIV Q563R 38 43 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. As observed for viral infectivity, at a concentration of 10mug/mL, mAb 240-D exhibited a 5-fold increase in virus-cell fusion of Q563R-expressing Env viruses. 2020 PLoS pathogens Result HIV Q563R 129 134 Env 146 149 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Based on these data, we propose a model in which the Q563R change in the Env E1 disrupts the HR1-HR2 interaction required for six-helix bundle formation (Fig 7). 2020 PLoS pathogens Result HIV Q563R 53 58 Env 73 76 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. In contrast, the presence of the Q563R change increased virus inhibition by D5 (IC50 values of 8mug/mL for Env E1 and 0.6mug/mL for Env NE1 Q563R). 2020 PLoS pathogens Result HIV Q563R 33 38 Env;Env 107;132 110;135 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. In contrast, the Q563R change rendered both E1 and NE1 Q563R viruses ~10-fold more sensitive to C34 inhibition, with IC50 values of 0.05mug/mL and 0.04mug/mL, respectively (Fig 4C). 2020 PLoS pathogens Result HIV Q563R 17 22 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. On the same lines, the R Q substitution in Env E1 R563Q virus did not support increased infectivity, and reverted to the phenotype seen with Env NE1 virus, indicating that the Q563R change mediated increased infectivity even in the presence of neutralizing antibodies in HIV positive plasma (S3 Fig). 2020 PLoS pathogens Result HIV Q563R 176 181 Env;Env 43;141 46;144 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Proposed model for the rescue of a Q563R-mediated infectivity defect by HR1-targeting antibodies. 2020 PLoS pathogens Result HIV Q563R 35 40 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Q563R allows for better binding of MPER bNAbs. 2020 PLoS pathogens Result HIV Q563R 0 5 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Specifically, Env with a single leucine to serine substitution in gp41 at position 669 (L669S) showed increased neutralization by MPER bNAbs 2F5 and 4E10, presumably via prolonged exposure of these relevant epitopes. 2020 PLoS pathogens Result HIV L669S 88 93 gp41;Env 66;14 70;17 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. The Q563R change dramatically decreases viral infectivity by disrupting membrane fusion and six-helix bundle formation. 2020 PLoS pathogens Result HIV Q563R 4 9 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. The R563Q substitution in E1 R563Q rendered the virus >10-fold resistant to the MPER bNAb Z13e1 (Fig 6D). 2020 PLoS pathogens Result HIV R563Q 4 9 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Therefore, through the testing of chimeric Envs and point mutants we have identified a single-residue change in gp41, Q563R, that is responsible for the HIV-1-positive plasma-dependent increase in infection observed for viruses with Env E1. 2020 PLoS pathogens Result HIV Q563R 118 123 gp41;Env;Env 112;43;233 116;47;236 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. These data indicate that the Q563R change allows for better recognition by the rare, difficult-to-induce MPER bNAbs. 2020 PLoS pathogens Result HIV Q563R 29 34 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Thus, our results suggest that specific antibodies targeting a narrow 592LLGIW596 epitope within the gp41 C-C loop may help stabilize six-helix bundle formation and restore virus infectivity disrupted by the Q563R change (S5D Fig). 2020 PLoS pathogens Result HIV Q563R 208 213 gp41 101 105 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Thus, the Q563R substitution in the E1 and NE1 Q563R Envs increased accessibility of C34 to gp41, potentially indicating disruption of the six-helix bundle. 2020 PLoS pathogens Result HIV Q563R 10 15 gp41;Env 92;53 96;57 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. To confirm the specificity of gp41-binding antibodies that mediate increased infectivity of viruses with Q563R-containing Envs, we tested infection in the presence of HR2-binding antibodies 98-6 and NC-1. 2020 PLoS pathogens Result HIV Q563R 105 110 gp41;Env;NC 30;122;199 34;126;201 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Viruses with Env NE1 Q563A failed to exhibit the increase in infection seen with Q563R. 2020 PLoS pathogens Result HIV Q563R 81 86 Env 13 16 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Viruses with the Q563R variant of Env NE1 exhibited the same increased infection as Env E1 in the presence of autologous HIV-1-positive plasma. 2020 PLoS pathogens Result HIV Q563R 17 22 Env;Env 34;84 37;87 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. We aimed to determine whether the Q563R-mediated effects on Env conformation affected neutralization by the rare bNAbs targeting the gp41 region. 2020 PLoS pathogens Result HIV Q563R 34 39 gp41;Env 133;60 137;63 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). Among participants without historical lamivudine resistance, none presented the K65R/E/N mutation but in three and seven cases the M184I mutation was detected with over a 5% or 1% threshold, respectively, including one participant harboring the M184I mutation with a 99% frequency. 2020 EBioMedicine Result HIV K65E;K65N;K65R;M184I;M184I 80;80;80;131;245 88;88;88;136;250 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). Seven participants with historical lamivudine resistance had the M184V/I and/or K65R/E/N mutations detected over the 20% threshold at baseline by next generation sequencing. 2020 EBioMedicine Result HIV K65E;K65N;K65R;M184I;M184V 80;80;80;65;65 88;88;88;72;72 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). Three of the six participants without historical lamivudine resistance who had transient low-level viral rebound had the M184I mutation detected through next-generation sequencing in baseline proviral DNA, including the participant who had this mutation detected at a frequency above 99%. 2020 EBioMedicine Result HIV M184I 121 126 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). Two participants in the history of lamivudine resistance group -initially misclassified as lacking lamivudine resistance-associated mutations- had the M184V mutation detected in proviral DNA Sanger sequencing at baseline (protocol violation). 2020 EBioMedicine Result HIV M184V 151 156 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). We were able to obtain Sanger sequencing in two participants with history of M184V/I mutation who had a transient viral rebound, including one individual rebounding to 1120 copies/mL at week 36 (Figure 3): there was no re-emergence of lamivudine-resistance associated mutations nor did we identify any newly acquired integrase mutations. 2020 EBioMedicine Result HIV M184I;M184V 77;77 84;84 IN 317 326 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Among patients with M184V mutation, two had mutations at position 138 of reverse transcriptase that is associated with low-level resistance to the NNRTI, rilpivirine, and three had major mutations (Y143C, N155H, T66I, G118R, E138K) conferring high level resistance to RAL (Table 2). 2020 Antiviral chemistry & chemotherapy Result HIV E138K;G118R;M184V;N155H;T66I;Y143C 225;218;20;205;212;198 230;223;25;210;216;203 RT;NNRTI 73;147 94;152 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Furthermore, accessory mutations potentially associated with low level resistance to InSTIs accompanied the reverse transcriptase M184V mutation in three patients. 2020 Antiviral chemistry & chemotherapy Result HIV M184V 130 135 RT;INSTI 108;85 129;91 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. However, before starting the salvage therapy, the HIV-1 sequence had the polymorphic T97A mutation that has usually minimal effects on RAL susceptibility, and the E138Q mutation associated with low level resistance to the NNRTI, rilpivirine. 2020 Antiviral chemistry & chemotherapy Result HIV E138Q;T97A 163;85 168;89 NNRTI 222 227 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. However, following RAL-based therapy, the polymorphic mutations disappeared, the NRTI mutation, M184V, occurred in all four patients, while RAL-associated mutations were observed in two patients, "5" and "6" (Table 2). 2020 Antiviral chemistry & chemotherapy Result HIV M184V 96 101 NRTI 81 85 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. M184V mutation associated with high level resistance to lamivudine (3TC) and FTC was detected in six out of seven patients (Table 2). 2020 Antiviral chemistry & chemotherapy Result HIV M184V 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Thereafter, the M184V mutation that is associated with resistance to NRTIs was detected within 32 weeks of treatment with RAL and Kivexa (abacavir/3TC), while the T97A and E138Q mutations disappeared at 48 weeks of treatment. 2020 Antiviral chemistry & chemotherapy Result HIV E138Q;M184V;T97A 172;16;163 177;21;167 NRTI 69 74 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. In one case, we detected an additional NRTI drug resistance mutation (M184V) (Table 2). 2020 AIDS research and therapy Result HIV M184V 70 75 NRTI 39 43 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. The most common PDR was K103N (5.6%, 11/197), followed by Y181C (3.6%, 7/197). 2020 AIDS research and therapy Result HIV K103N;Y181C 24;58 29;63 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. We identified the accessory mutation E138A in eight samples. 2020 AIDS research and therapy Result HIV E138A 37 42 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. 4) with average distances of (Y188/P227) 4.4 +- 0.6/3.3 +- 0.6 A for WT RT, 3.9 +- 0.4/3.4 +- 0.6 A for the K103N variant, and 4.5 +- 0.7/4.7 +- 0.7 A for the K103N/Y181C mutated enzyme. 2020 Acta pharmaceutica Sinica. B Result HIV K103N;K103N;Y181C 108;159;165 113;164;170 RT 72 74 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. All the compounds were further evaluated against a panel of clinically relevant NNRTIs-resistant single-mutant strains (L100I, K103N, Y181C, Y188L, E138K) and double-mutant strains F227L + V106A, RES056. 2020 Acta pharmaceutica Sinica. B Result HIV E138K;F227L;K103N;L100I;V106A;Y181C;Y188L 148;181;127;120;189;134;141 153;186;132;125;194;139;146 NNRTI 80 86 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. As noted in the Experimental Section of this work, a similar (EC50 = 9.93 and 6.02 nmol/L) inhibitory activity was found by 26 in the WT and the single mutant K013N, whereas it was 20-fold less potent (EC50 = 125 nmol/L) against the double mutant RES056. 2020 Acta pharmaceutica Sinica. B Result HIV K013N 159 164 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Compound 26 demonstrated the most active potency toward all the single-mutant HIV-1 strain, including L100I, K103N, Y181C, Y188L and E138K (EC50 = 10.5, 6.02, 18.9, 23.9 and 23.2 nmol/L, respectively), its activity was superior to that of NVP and EFV, and comparable to that of ETR. 2020 Acta pharmaceutica Sinica. B Result HIV E138K;K103N;L100I;Y181C;Y188L 133;109;102;116;123 138;114;107;121;128 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. For double-mutant HIV-1 strain F227L + V106A, compounds 23 and 27 were proved to be the most potent inhibitors and exhibited EC50 values of 46.6 and 49.2 nmol/L, respectively, being far more potent than NVP (EC50 > 9510 nmol/L) and EFV (EC50 = 268 nmol/L), and comparable to ETR (EC50 = 14.2 nmol/L). 2020 Acta pharmaceutica Sinica. B Result HIV F227L;V106A 31;39 36;44 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. For example, 26 displayed the most effective activity against K103N (EC50 = 6.02 nmol/L, FR = 0.6), being more potent than its activity to WT HIV-1 (EC50 = 9.93 nmol/L). 2020 Acta pharmaceutica Sinica. B Result HIV K103N 62 67 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. In this regard, binding affinities (DeltaGbind) of -73.4 and -74.1 kcal/mol were obtained respectively for the WT HIV-1 RT and the K103N mutant (Table 5), whereas a binding free energy of -65.9 kcal/mol was observed for 26 in the NNIBP of the double mutant RES056. 2020 Acta pharmaceutica Sinica. B Result HIV K103N 131 136 RT 120 122 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Interestingly, all the target compounds displayed lower fold resistance (FR, ratio of EC50 against mutant strain/EC50 against WT strain) values toward K103N than other mutant strains. 2020 Acta pharmaceutica Sinica. B Result HIV K103N 151 156 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Most compounds were demonstrated with improved activity against K103N mutation compared to WT strain. 2020 Acta pharmaceutica Sinica. B Result HIV K103N 64 69 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. The complexes of 26 with WT, K103N or RES056 RT display the following common interactions: (i) the newly introduced biphenyl structure is stably accommodated into the hydrophobic channel and stabilized by pi-stacking interactions with Y/C181, Y188, F227, and W229; (ii) the thiophene ring of 26 is projected towards the NNIBP entrance channel surrounded by V179 and E138; and (iii) the piperidine-linked benzamide structure of the right wing occupies the tolerant region I surrounded by K/N103, K104, V106, and F227. 2020 Acta pharmaceutica Sinica. B Result HIV K103N 29 34 PI;RT 205;45 207;47 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. To this end, the X-ray crystal structure of the WT HIV-1 RT (PDB code: 6c0n), and its K103N (PDB code: 6c0o) and RES056 (K103N/Y181C) (PDB code: 6c0r) variants were used. 2020 Acta pharmaceutica Sinica. B Result HIV K103N;K103N;Y181C 86;121;127 91;126;132 RT 57 59 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. As reported, HIV-1 GFP R9 bearing CA mutant N74D, which does not bind the cellular cofactor CPSF6, was insensitive to MxB (Figure 2A,B) and MxB induction did not strongly suppress infection (Figure 2A), viral DNA synthesis, or 2LTR circle formation (Figure 2B). 2020 eLife Result HIV N74D 44 48 Capsid 34 36 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. For example, MxB-insensitive CA mutant N74D is insensitive to depletion of HIV-1 nuclear entry cofactors Nup358, TNPO3, CPSF6 and to some degree Nup153. 2020 eLife Result HIV N74D 39 43 Capsid 29 31 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. HIV-1 bearing CA mutant P90A, which alters the otherwise completely conserved CypA binding site and causes reduced interaction with CypA and Nup358, is completely insensitive to MxB restriction. 2020 eLife Result HIV P90A 24 28 Capsid 14 16 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. HIV-1 bearing CA P90A, which alters the otherwise completely conserved CypA binding site and reduces CA affinity for CypA and Nup358, is completely insensitive to MxB restriction and also has reduced sensitivity to depletion of Nup358, TNPO3 and CPSF6. 2020 eLife Result HIV P90A 17 21 Capsid;Capsid 14;101 16;103 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. HIV-1 sensitivity to MxB in the presence of CsA was also rescued by a second CsA escape mutant G94D (Figure 3J), which is also thought to recapitulate the effect of CypA binding by stabilising the CypA binding loop. 2020 eLife Result HIV G94D 95 99 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Importantly, the A92E CA mutation also rescued MxB sensitivity in the absence of CypA protein, after shRNA-mediated CypA depletion, and after CypA inhibition with CsA (Figure 3H and I). 2020 eLife Result HIV A92E 17 21 Capsid 22 24 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Importantly, the double mutation HIV-1 R9 CA G116Q, H120G was not particularly different from the wild type HIV-1 R9 in either sensitivity to MxB or CsA indicating that the TQPI mutations are required to achieve the 93BR029 phenotype. 2020 eLife Result HIV G116Q;H120G 45;52 50;57 Capsid 42 44 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. In a control experiment, HIV-1 CA P90A was treated with CsA during infection of MxB expressing cells and we observed no rescue to infectivity, consistent with P90A being resistant to MxB due to failure to recruit CypA (Figure 3F). 2020 eLife Result HIV P90A;P90A 34;159 38;163 Capsid 31 33 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. In fact, adding A92E to HIV-1 CA P90A rescued sensitivity to MxB. 2020 eLife Result HIV A92E;P90A 16;33 20;37 Capsid 30 32 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. The A92E mutation was identified by selection of HIV-1 replicating mutants during CypA inhibition with CsA. 2020 eLife Result HIV A92E 4 8 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. These data demonstrate that, for this particular HIV-1 isolate (HIV-1 R9), it is not CypA recruitment per se that is required for MxB sensitivity, but rather the conformational effect of CypA recruitment, likely the CypA mediated stabilisation of the CypA binding loop, which is recapitulated by the A92E and G94D mutations. 2020 eLife Result HIV A92E;G94D 300;309 304;313 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. This is informative because, like CA mutation N74D, CPSF6 depletion reduces HIV-1 R9 sensitivity to depletion of nuclear entry associated cofactors without impacting infectivity. 2020 eLife Result HIV N74D 46 50 Capsid 34 36 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Thus, HIV-1 bearing CA A92E infects HEK293 cells efficiently, in the absence of CypA recruitment, enabling us to test whether CypA recruitment, or the conformational effect of CypA binding, is required for MxB sensitivity. 2020 eLife Result HIV A92E 23 27 Capsid 20 22 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Thus, MxB induction with dox restricted HIV-1 CA P90A A92E but not HIV-1 bearing CA P90A alone (Figure 3G). 2020 eLife Result HIV A92E;P90A;P90A 54;49;84 58;53;88 Capsid;Capsid 46;81 48;83 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. TNPO3 depletion also did not affect the sensitivity of HIV-1 CA P90A to MxB, which was insensitive to TNPO3 depletion as described (; Figure 2F). 2020 eLife Result HIV P90A 64 68 Capsid 61 63 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. To distinguish between these two possibilities, we combined mutation A92E with P90A on HIV-1 CA and examined MxB sensitivity. 2020 eLife Result HIV A92E;P90A 69;79 73;83 Capsid 93 95 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. To establish their contribution to MxB sensitivity we made the HIV-1 R9 GFP quadruple mutant V86T, H87Q, A92P M96I (named 'TQPI') to mimic the 93BR020 sequence in the CypA binding loop in CA and measured TQPI sensitivity to inhibition by CsA and MxB (Figure 4D). 2020 eLife Result HIV A92P;H87Q;M96I;V86T 105;99;110;93 109;103;114;97 Capsid 188 190 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. To our knowledge this is the first occasion in which the effects of CPSF6 depletion and CA N74D mutation on HIV-1 infection differ. 2020 eLife Result HIV N74D 91 95 Capsid 88 90 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. To test whether HIV-1 CA N74D insensitivity is due to its different mechanism of nuclear entry, we measured the effect of CPSF6 depletion on MxB sensitivity of wild type HIV-1 GFP R9. 2020 eLife Result HIV N74D 25 29 Capsid 22 24 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Together, these observations suggest that HIV-1 bearing CA N74D is insensitive to MxB as a direct result of the CA mutation and not due to loss of CPSF6 recruitment. 2020 eLife Result HIV N74D 59 63 Capsid;Capsid 56;112 58;114 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. We therefore added G116Q and H120G to the HIV-1 R9 GFP CA TQPI to make HIV-1 GFP CA TQPIQG and again tested sensitivity to restriction by MxB and CsA (Figure 4D). 2020 eLife Result HIV G116Q;H120G 19;29 24;34 Capsid;Capsid 55;81 57;83 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. We verified that HIV-1 CA P90A is insensitive to MxB demonstrating no reduction in HIV-1 P90A infectivity (Figure 3A), 2LTR or proviral DNA levels (Figure 3B) after induction of MxB expression. 2020 eLife Result HIV P90A 26 30 Capsid 23 25 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. A quarter (9/36 [25%]) of the samples contained both M184V and K103N mutations. 2020 PloS one Result HIV K103N;M184V 63;53 68;58 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. Both groups of patients were on similar regimens and displayed similar genotypic resistance profiles, with the K103N (>=57%) and M184V (>=71%) mutations being the most prevalent. 2020 PloS one Result HIV K103N;M184V 111;129 116;134 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. The most predominant NRTI mutation was M184V (18/36 [50%]). 2020 PloS one Result HIV M184V 39 44 NRTI 21 25 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. The most prevalent NNRTI mutations were K103N (16/36 [44%]) and V106M (9/36 [25%]). 2020 PloS one Result HIV K103N;V106M 40;64 45;69 NNRTI 19 24 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. The prevalence of other major NNRTI resistance mutations (Y181CS, Y188CH, G190A and M230L) was <=8%. 2020 PloS one Result HIV G190A;M230L;Y181C;Y181S;Y188C;Y188H 74;84;58;58;66;66 79;89;64;64;72;72 NNRTI 30 35 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. Those with M184V mutation (33/43 [77%]) had a reduced susceptibility to 3TC (FC = 9.8, the limit of the assay), while those without M184V were fully susceptible (10/43 [23%], FC<=1.5) (S2 Table). 2020 PloS one Result HIV M184V;M184V 11;132 16;137 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Also, we found NCS mutations at positions V370A/M in p2 (PT3, PT5 and PT6) and I389T in p7 (PT2, PT3, PT4, PT5 and PT6). 2020 The Journal of antimicrobial chemotherapy Result HIV I389T;V370A;V370M 79;42;42 84;49;49 NC 15 17 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Also, we found variations at the helix 4/5 flap region (R91K, E93D and K95R) and helix 5 (K113Q). 2020 The Journal of antimicrobial chemotherapy Result HIV E93D;K113Q;K95R;R91K 62;90;71;56 66;95;75;60 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Also, we identified changes in p7/p1 at K436R and I437V positions, respectively, in PT5 and PT7. 2020 The Journal of antimicrobial chemotherapy Result HIV I437V;K436R 50;40 55;45 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. As shown in Figure 4(a), recombinant viruses from PT1, PT3 and PT6 were fully susceptible to darunavir in accordance with the high genetic barrier of the drug, even in the presence of I54V and V82A protease mutations, as predicted by Stanford for the T2 clonal viruses 5 and 8 from PT3. 2020 The Journal of antimicrobial chemotherapy Result HIV I54V;V82A 184;193 188;197 PR 198 206 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. At p2/p7, we found the mutation S373P in PT2 and PT6, the mutation A374S/P in PT3 and PT5 and the mutation T375A in PT4. 2020 The Journal of antimicrobial chemotherapy Result HIV A374P;A374S;S373P;T375A 67;67;32;107 74;74;37;112 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. At position 286 in p24, we identified the mutation R286K with a frequency of 78% in PI-treated patients and 35.5% in naive sequences (P < 0.01). 2020 The Journal of antimicrobial chemotherapy Result HIV R286K 51 56 p24;PI 19;84 22;86 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. At position 95 in p17, we found K95R present in 44% of PI-treated patients at VF in comparison with 12% of naive sequences (P < 0.01). 2020 The Journal of antimicrobial chemotherapy Result HIV K95R 32 36 PI 55 57 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Clonal sequences were also analysed using the Stanford HIVdb database, and clones were predicted to be PI susceptible, except the clones containing I52V and V82A, which were predicted to have intermediate resistance to lopinavir and be fully susceptibility to darunavir. 2020 The Journal of antimicrobial chemotherapy Result HIV I52V;V82A 148;157 152;161 PI 103 105 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. In p17, the residues were distributed at positions K28Q, E55G, G62E, R76K, R91K, E93D, K95R and K113Q (Figure 5a). 2020 The Journal of antimicrobial chemotherapy Result HIV E55G;E93D;G62E;K113Q;K28Q;K95R;R76K;R91K 57;81;63;96;51;87;69;75 61;85;67;101;55;91;73;79 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. In p24, we mapped mutational changes at helix 7 (L268M), at the linker between helix 7 and 8 (R268K) and at the helix 9/10 flap region (A326S) (Figure 5b). 2020 The Journal of antimicrobial chemotherapy Result HIV A326S;L268M;R268K 136;49;94 141;54;99 p24 3 6 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. In PT4, a single CS mutation was found at position S451N of p1/p6. 2020 The Journal of antimicrobial chemotherapy Result HIV S451N 51 56 Gag 63 65 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. In the case of PT3, we were able to detect a cluster of clonal sequences [C5, C6, C8 and C10 (Figure S1B)] containing drug resistance mutations I52V and V82A in the protease at T2. 2020 The Journal of antimicrobial chemotherapy Result HIV I52V;V82A 144;153 148;157 PR 165 173 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Moreover, we observed three additional amino acid differences (E107G in p17, T280A in p24 and E461G in p6) in the low-replicating susceptible variant T2C10 from PT4 (Table 4). 2020 The Journal of antimicrobial chemotherapy Result HIV E107G;E461G;T280A 63;94;77 69;99;82 p24;Gag 86;103 89;105 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Mutations R76K in p17, T375A in p2/p7 and S451N in p1/p6 were present, and have been previously associated with exposure to PIs in vivo but not directly with drug resistance to darunavir. 2020 The Journal of antimicrobial chemotherapy Result HIV R76K;S451N;T375A 10;42;23 14;47;28 Gag;PI 54;124 56;127 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Mutations were located between helix 1/2 (K28Q) and the globular domain of helix 3 (E55G, G62E), which are essential for protein structural stability and interactions with helix 4 (R76K) of p17. 2020 The Journal of antimicrobial chemotherapy Result HIV E55G;G62E;K28Q;R76K 84;90;42;181 88;94;46;185 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Of note, all the darunavir-resistant clonal variants harboured the K95R and R268K signature mutations identified by VESPA and both positions are involved in structural flexibility of p17 and p24 tertiary structures. 2020 The Journal of antimicrobial chemotherapy Result HIV K95R;R268K 67;76 71;81 p24 191 194 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Of note, for PT4 only three mutational changes in Gag (E107G, T280A and E461G) differentiated the high and the low replicative variants at T2 (Table 4). 2020 The Journal of antimicrobial chemotherapy Result HIV E107G;E461G;T280A 55;72;62 60;77;67 Gag 50 53 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Only non-polymorphic and polymorphic PI accessory selected mutations were found in PT1 (K20T), PT4 (A71V) and PT5 (L10V). 2020 The Journal of antimicrobial chemotherapy Result HIV A71V;K20T;L10V 100;88;115 104;92;119 PI 37 39 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Similarly, viruses from PT1, PT3 and PT6 were fully susceptible to lopinavir with the exception of the clonal viruses 5 and 8 from PT3 at T2 (Table 4), which carry I54V and V82A protease mutations able to replicate at 100 nM lopinavir (Figure 4b). 2020 The Journal of antimicrobial chemotherapy Result HIV I54V;V82A 164;173 168;177 PR 178 186 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. The R76K mutation was present in 57% of the cases of VF and the E12K/D mutation was present in PT2, PT5 and PT6. 2020 The Journal of antimicrobial chemotherapy Result HIV E12D;E12K;R76K 64;64;4 70;70;8 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Thus, VESPA provided the signature K95R and R286K in Gag. 2020 The Journal of antimicrobial chemotherapy Result HIV K95R;R286K 35;44 39;49 Gag 53 56 32576136 Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study. The most common mutations in NNRTIs were K103N/KN (64.69%), V179D/E (23.47%) and Y181C/YC/I (14.00%), they were M184V/MV/I (36.29%), T215F/FS/TNSY (7.50%) and K219Q (5.92%) in NRTIs, and they were Q58E/QE (4.93%), L10F/LFI (0.39%) and M46L (0.39%) in PIs. 2020 BMC infectious diseases Result HIV K103K;K103N;K219Q;L10F;L10I;L10L;M184I;M184M;M184V;M46L;Q58E;Q58Q;T215F;T215N;T215S;T215T;T215Y;V179D;V179E;Y181C;Y181I;Y181Y 41;41;159;214;214;214;112;112;112;235;197;197;133;133;133;133;133;60;60;81;81;81 48;48;164;220;220;220;122;122;122;239;203;204;146;146;146;146;146;67;67;91;91;91 NNRTI;NRTI;PI 29;176;251 35;181;254 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Antiviral activity and cytotoxicity of compounds 13 and 21 were determined at 5 days on MT4 cells against HIV-1 NL4.3 wt strain and HIV-1 NL4.3 carrying the K103N-Y181C double mutation, commonly selected in patients and that confers resistance to non-nucleoside RT inhibitors (NNRTIs). 2020 Viruses Result HIV K103N;Y181C 157;163 162;168 NNRTI;RT 277;262 283;264 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Both N-acylhydrazone derivatives inhibited viral replication retaining similar potency of inhibition against the NNRTI-resistant double mutant NL4-3 K103N-Y181C virus, similarly to AZT and RAL and the RNase H inhibitor RDS1759, while the NNRTIs lost their antiviral activity. 2020 Viruses Result HIV Y181C;K103N 155;149 160;154 NNRTI;NNRTI 113;238 118;244 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Differently, RDS1759 potency of inhibition was not significantly affected against RTs carrying the R448A or R557A mutations as compared to the wt RT (p-values equal to 0.5545 and 0.9682, respectively) while it significantly lost its potency when tested on the Q475A RT (p-value = 0.0008). 2020 Viruses Result HIV Q475A;R448A;R557A 260;99;108 265;104;113 RT;RT;RT 82;146;266 85;148;268 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Hence, the single point mutations R448A, Q475A and R557A were independently introduced in the HIV-1 pol and mutant R448A-, Q475A- and R557A-RT were expressed and purified. 2020 Viruses Result HIV Q475A;Q475A;R448A;R448A;R557A;R557A 41;123;34;115;51;134 46;128;39;120;56;139 Pol;RT 100;140 103;142 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. The IC50 value increases of 5.2-fold against Q475A (p-value = 0.0003); 9.2-fold against R448A (p-value <0.0001) and more than 16.2-fold against R557A (p-value < 0.0001). 2020 Viruses Result HIV Q475A;R448A;R557A 45;88;144 50;93;149 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. In four (4) of the patients carrying resistance associated mutations in the urban setting, 6 resistance mutations to NRTIs: [M41L (2), E44D (1), K65R (1), K70E (1), M184V/I (2), K219R (1)] and 6 resistance mutations to NNRTIs: K103N (1), E138A/G (2), V179E (1), M230L (1), K238T (1), P225H (1)] were found. 2020 PloS one Result HIV E138A;E138G;E44D;K103N;K219R;K238T;K65R;K70E;M184I;M184V;M230L;M41L;P225H;V179E 238;238;135;227;178;273;145;155;165;165;262;125;284;251 245;245;139;232;183;278;149;159;172;172;267;129;289;256 NNRTI;NRTI 219;117 225;122 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. In the two patients carrying resistance mutations in the samples from the rural setting, resistance mutations to only NNRTIs E138A (1) and Y188H (1)] were found. 2020 PloS one Result HIV E138A;Y188H 125;139 130;144 NNRTI 118 124 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. No major PR-related DRM was observed in the samples whilst major RT-related DRMs in two (2) samples were found; E138A in one sample and another with K65R. 2020 Virology journal Result HIV E138A;K65R 112;149 117;153 PR;RT 9;65 11;67 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. Thus, limited self-peptide binding by Ld 97W is reversed by the Ld W97R mutation, allowing for higher cell surface expression. 2020 Frontiers in immunology Result HIV W97R 67 71 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. To confirm that the changes in IE1-Ld specific T cells are a direct consequence of the W97R mutation, we examined another immunodominant response restricted to a different MHC-1 molecule (m164-Dd). 2020 Frontiers in immunology Result HIV W97R 87 91 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. To extend these studies to an in vivo setting, we used CRISPR-EZ to generate mice in which the controller-associated tryptophan at position 97 of Ld is converted to a progressor-associated arginine residue (Ld W97R mutation) (Figure 4A). 2020 Frontiers in immunology Result HIV W97R 210 214 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. To further explore the connection between limited peptide binding by MHC and robust CD8+ T cell responses, we investigated the effect of the Ld W97R mutation in the setting of persistent infection. 2020 Frontiers in immunology Result HIV W97R 144 148 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Additionally, 3 INSTI-naive patients had accessory mutations: E157Q (2/183; 1.1%) and T97A (1/183; 0.5%), which alone have minimal impact on INSTI susceptibility or HIV-1 replication capacity. 2020 Viruses Result HIV E157Q;T97A 62;86 67;90 INSTI;INSTI 16;141 21;146 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Additionally, given that the majority of A1 sequences, which are the source of A6, do not have any substitutions in codon 74, the overall picture is that L74I was selected at the early stage of the epidemic among injectors in Russia and subsequently spread as a founder effect in Russia and other regions. 2020 Viruses Result HIV L74I 154 158 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. At this position, for the vast majority of sequences of sub-subtype A6, the codon ATA was present, which determined the genetic barrier for L74M (score of 1) and L74I (score of 0). 2020 Viruses Result HIV L74I;L74M 162;140 166;144 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Clearly, the viruses with the L74I mutation spread as a result of a founder effect among injectors across FSU countries. 2020 Viruses Result HIV L74I 30 34 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. EF545108) with L74L were placed close to the root of the A6 tree. 2020 Viruses Result HIV L74L 15 19 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Five highly polymorphic mutations, R20K, I72V, L74I, S119P, and V201I, were frequently reported in regard to a small reduction in replication capacity relative to the wild type. 2020 Viruses Result HIV I72V;L74I;R20K;S119P;V201I 41;47;35;53;64 45;51;39;58;69 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. For position L74F, A6 sequences had a score of 5, while for sequences of A1 and B, the barrier had a score of 3.5. 2020 Viruses Result HIV L74F 13 17 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Founder Effect of the L74I Mutation. 2020 Viruses Result HIV L74I 22 26 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Interestingly, position 124 had different highly polymorphic mutations in the A1 (T124A) and A6 (T124S) sequences. 2020 Viruses Result HIV T124A;T124S 82;97 87;102 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Interestingly, there was a small separate cluster of viruses with L74M, including 7 samples from Uzbekistan, one sample from Russia (Tomsk), and one sample from Kuwait. 2020 Viruses Result HIV L74M 66 70 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Only one mutation, R263K, was in the list of SDRMs. 2020 Viruses Result HIV R263K 19 24 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Other mutations (T124S, S255N) have not been previously reported. 2020 Viruses Result HIV S255N;T124S 24;17 29;22 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Sub-subtype A6 and other genetic variants of subtype A included L74L in 3.7% and 86.4% of cases, L74I in 94.9% and 9.6%, L74M in 1.2% and 3%, and L74V in 0.1% and 1%, respectively. 2020 Viruses Result HIV L74I;L74L;L74M;L74V 97;64;121;146 101;68;125;150 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The 9 amino acid substitutions (V31I, T112V, I113V, T125A, G134N, K136Q, D167E, T218I, and L234I) were described as polymorphic mutations in non-B clades, none of which were ascribed to INSTI resistance. 2020 Viruses Result HIV D167E;G134N;I113V;K136Q;L234I;T112V;T125A;T218I;V31I 73;59;45;66;91;38;52;80;32 78;64;50;71;96;43;57;85;36 INSTI 186 191 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The L74I mutation appears to be a key characteristic of sub-subtype A6. 2020 Viruses Result HIV L74I 4 8 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The major mutation, Q146P, was accompanied by the accessory mutation G163R in one patient and by itself in the second patient. 2020 Viruses Result HIV G163R;Q146P 69;20 74;25 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The sequences with L74L belonged to heterosexuals, identified before the burst of the large epidemic among the injectors. 2020 Viruses Result HIV L74L 19 23 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The third patient had only the accessory mutation G163R. 2020 Viruses Result HIV G163R 50 55 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Therefore, for the V151I mutation, which could play a role in the resistance to INSTIs, for both sub-subtypes A1 and A6, the genetic barrier was also higher than that of subtype B (0.4 versus 0.2, respectively). 2020 Viruses Result HIV V151I 19 24 INSTI 80 86 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. These codons determine that, with respect to subtype B, the calculated barrier for the G140C mutation, which is a major mutation and associated with resistance to all INSTIs, was equal to 2.5, and a score of 5 was calculated for subtype A. 2020 Viruses Result HIV G140C 87 92 INSTI 167 173 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Two of the patients had major mutations, including R263K (1/183; 0.5%), which was associated with intermediate-level DTG, EVG resistance, and low-level RAL, BIC resistance, and unusual mutation in DR-position S147T, which does not reduce susceptibility to any INSTI. 2020 Viruses Result HIV R263K;S147T 51;209 56;214 INSTI 260 265 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Within the A6 subcluster, there are a few branches with L74L, suggesting that in a few cases, L74I can revert to wild type. 2020 Viruses Result HIV L74I;L74L 94;56 98;60 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. However, the H196Q variant is predicted to disrupt a salt bridge between H196 and tetherin residue D15 as assessed using PISA (Proteins, Interfaces, Structures, and Assemblies) software, suggesting disruption of a direct interaction between Nef and tetherin may contribute to the selective disadvantage of this change. 2020 PloS one Result HIV H196Q 13 18 Nef 241 244 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. N-fold analysis of tetherin downregulation in cells from multiple animals demonstrated significant loss of downregulation in the virus harboring only H196Q, while the addition of E191R restored this ability to wild type levels (Fig 2B). 2020 PloS one Result HIV E191R;H196Q 179;150 184;155 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Viruses harboring H196Q alone were largely deficient in tetherin downregulation, as expected. 2020 PloS one Result HIV H196Q 18 23 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. We introduced the E191R variant along with the H196Q onto the SIVmac239 backbone to assess tetherin downregulation. 2020 PloS one Result HIV E191R;H196Q 18;47 23;52 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. We next used the Rotamers function in UCSF Chimera to determine whether the H196Q variant impacted interactions with AP-2. 2020 PloS one Result HIV H196Q 76 81 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. When E191R was introduced along with H196Q, the resulting virus showed full competency in tetherin downregulation, similar to SIVmac239 (Fig 2A). 2020 PloS one Result HIV E191R;H196Q 5;37 10;42 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Additionally, 13.3% (6 out of the 45) needing first line drug change had the type 2 TAMs combination of T215Y, D67N and K70RTQNE which in combination diminish the effectiveness of zidovudine. 2020 PloS one Result HIV D67N;K70E;K70N;K70Q;T215Y 111;120;120;120;104 115;128;128;128;109 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Among the NRTI mutations, the most common Thymidine Analogue Mutations (TAM's) were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%), T215IT (15.5%) and M41L (5.2%). 2020 PloS one Result HIV D67N;K219E;K219Q;K70E;K70N;K70Q;M41L;T215I;T215T 118;102;102;84;84;84;151;132;132 122;108;108;92;92;92;155;138;138 NRTI 10 14 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Of these (n = 45), 19 had the K65R mutation that confers resistance to tenofovir and abacavir but potentiates the effectiveness of zidovudine as a second line option. 2020 PloS one Result HIV K65R 30 34 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Overall, the 10 most common mutations were M184V (81%), K103N (65.5%), Y188C (36.2%), Y181C (36.2%), V106A (36.2), K65R (34.5%), K70RTQNE (32.8%), G190ASV (31.0%), K101EHP (31.0%) and E138AGQ (29.3%). 2020 PloS one Result HIV E138A;E138G;E138Q;G190A;G190S;G190V;K101E;K101H;K101P;K103N;K65R;K70E;K70N;K70Q;M184V;V106A;Y181C;Y188C 184;184;184;147;147;147;164;164;164;56;115;129;129;129;43;101;86;71 191;191;191;154;154;154;171;171;171;61;119;137;137;137;48;106;91;76 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The N88S was the only major PI mutation (1.7%) and there were three PI-Accessory mutations of L10LF (1.7%), K20T (1.7%) and Q58E (5.2%). 2020 PloS one Result HIV K20T;L10F;L10L;N88S;Q58E 108;94;94;4;124 112;99;99;8;128 PI;PI 28;68 30;70 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The prevalence of mutations Y188C and Y181C was at 36.2% for and these (individually or in concert) confer resistance to the NNRTI drug etravirine. 2020 PloS one Result HIV Y181C;Y188C 38;28 43;33 NNRTI 125 130 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The ten most common mutations to the drug class NNRTI included K103N (65.5%), V106A (36.2%), Y188C/L (36.2%), Y181C/V(36.2%), G190ASV(31%), K101EHP(31%), E138AGQ(29.3%), A98G(22.4%), P225H(20.7%), and V108I(17.2%). 2020 PloS one Result HIV A98G;E138A;E138G;E138Q;G190A;G190S;G190V;K101E;K101H;K101P;K103N;P225H;V106A;V108I;Y181C;Y181V;Y188C;Y188L 170;154;154;154;126;126;126;140;140;140;63;183;78;201;110;110;93;93 174;161;161;161;133;133;133;147;147;147;68;188;83;206;117;117;100;100 NNRTI 48 53 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. A virus carrying an inactivating mutation at the active site of the protease (D25N) was used as a negative control, which resulted in a complete abolishment of viral infectivity (Figure S2). 2020 International journal of molecular sciences Result HIV D25N 78 82 PR 68 76 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. A Western blot was then carried out in order to qualitatively determine whether the Y44A Tat mutation had any effect on the quantity of RT packaged into the virions. 2020 International journal of molecular sciences Result HIV Y44A 84 88 Tat;RT 89;136 92;138 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Additionally, more remarkable decrease of protein stability was predicted for Y44A and Y44G mutations as compared to other mutations (Figure 2c). 2020 International journal of molecular sciences Result HIV Y44A;Y44G 78;87 82;91 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. After 24 h, we noticed that the amount of RT was lower in the presence of Y44A mutation compared to that found in the wild-type, and after 3 days, RT was minimally detected (Figure 6b). 2020 International journal of molecular sciences Result HIV Y44A 74 78 RT;RT 42;147 44;149 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. An ELISA-based colorimetric reverse transcriptase assay was used to determine whether Y44A mutation had an effect on RT activity. 2020 International journal of molecular sciences Result HIV Y44A 86 90 RT;RT 28;117 49;119 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Effects of Y44A and Y55A Mutations on RT Activity. 2020 International journal of molecular sciences Result HIV Y44A;Y55A 11;20 15;24 RT 38 40 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Fluorescence-activated cell sorting (FACS) and fluorescent microscopy were used to analyze the transfection efficiency, which ranged from 70-75% for both vectors carrying mutant tat (Y44A and Y55A), similar to that observed for the wild-type vector. 2020 International journal of molecular sciences Result HIV Y44A;Y55A 183;192 188;196 Tat 178 181 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Furthermore, a Y55A mutant was also studied for comparison. 2020 International journal of molecular sciences Result HIV Y55A 15 19 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. GFP fluorescence signal indicating transactivation was significantly decreased by more than 93% and 91% in the presence of HIV-2 Tat Y44A and Y55A mutations, respectively (p value < 0.0001), compared to that of the wild-type (Figure 4a). 2020 International journal of molecular sciences Result HIV Y44A;Y55A 133;142 137;146 Tat 129 132 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Interestingly, we were not able to detect RT in the presence of Y44A mutant Tat from the lysate of pseudovirions (Figure 6a). 2020 International journal of molecular sciences Result HIV Y44A 64 68 Tat;RT 76;42 79;44 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Mutation of the large and polar Tyr sidechain (Y44A) to a small hydrophobic Ala was predicted to result in a loss of potentional hydrogen bond interactions. 2020 International journal of molecular sciences Result HIV Y44A 47 51 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Out of the above mentioned six residues, we assumed that Y44A mutation may have the most remarkable effect destabilizing the protein. 2020 International journal of molecular sciences Result HIV Y44A 57 61 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Percentage of fluorescent cells indicating successful transduction did not change significantly upon Y44A and Y55A mutations, as compared to the wild-type HIV-2 (p values 0.95 and 0.44, respectively). 2020 International journal of molecular sciences Result HIV Y44A;Y55A 101;110 105;114 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Pseudovirion production yielded viral titers of 16-18 ng/mL for wild-type and mutant virions, as determined by a colorimetric SIV p27 assay, and no significant difference was observed in terms of the amount of capsid between the HIV-2 wild-type and Y44A/Y55A Tat mutant pseudovirions. 2020 International journal of molecular sciences Result HIV Y44A;Y55A 249;254 253;258 Capsid;Tat 210;259 216;262 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Pseudovirions produced using vectors coding for the Y44A and Y55A Tat mutations had significantly diminished RT activity (3% and 4%, respectively) compared to that of the wild-type (p values < 0.0001), implying a detrimental effect of the mutations on the activity of RT (Figure 5). 2020 International journal of molecular sciences Result HIV Y44A;Y55A 52;61 56;65 Tat;RT;RT 66;109;268 69;111;270 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Secondary structure prediction implied more remarkable effects of Y44A mutation, compared to that of Y55A. 2020 International journal of molecular sciences Result HIV Y44A;Y55A 66;101 70;105 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The effects of point mutations on protein stability were also compared, and were found to be similar in the case of Y44A and Y55A mutations (Figure 2d). 2020 International journal of molecular sciences Result HIV Y44A;Y55A 116;125 120;129 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The inactivating effect of Y55A mutation on Tat protein was previously reported for SIV, therefore, the effects of the Y44A point mutation were compared to those of the previously characterized Y55A. 2020 International journal of molecular sciences Result HIV Y44A;Y55A;Y55A 119;27;194 123;31;198 Tat 44 47 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The predicted destabilizing nature of alanine substitution, and the conserved nature of the Tyr residue in the 44th position, implied that Y44A mutation may potentially be able to induce adverse changes to protein structure, and result in the inactivation of HIV-2 Tat. 2020 International journal of molecular sciences Result HIV Y44A 139 143 Tat 265 268 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. To explore the effects of Y44A mutation on the protein function, an HIV-2 vector carrying the modified tat gene was prepared and used for in vitro experiments. 2020 International journal of molecular sciences Result HIV Y44A 26 30 Tat 103 106 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Values determined by three different methods showed decreased protein stability for the Y44A mutant, based on analysis of both model structures. 2020 International journal of molecular sciences Result HIV Y44A 88 92 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. We transfected HEK293T cells with wild-type and Y44A mutant Tat coding HIV-2 CGP plasmids, thereafter, we followed changes in RT quantity by Western blot of transfected cell lysate over a period of 3 days. 2020 International journal of molecular sciences Result HIV Y44A 48 52 Tat;RT 60;126 63;128 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. While FoldX prediction implied increased stability for Y55A mutation, the destabilizing changes in Y55A mutant were predicted to be more remarkable as compared to Y44A. 2020 International journal of molecular sciences Result HIV Y44A;Y55A;Y55A 163;55;99 167;59;103 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. While we predicted putative disruption of the alpha-helix at the N-terminal part of the globular region for both mutations, predictions showed a higher probability for helical arrangement of the Cys-rich domain as a result of Y44A mutation (Figure 3). 2020 International journal of molecular sciences Result HIV Y44A 226 230 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Y26A and Y55A mutations were previously found to result in the inactivation of HIV-1 and SIV Tat proteins, respectively. 2020 International journal of molecular sciences Result HIV Y55A;Y26A 9;0 13;4 Tat 93 96 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. Despite no drug resistance-related major mutations were identified, several drug resistance-related minor mutations including M36I [amino acid substitution from methionine (M) to isoleucine (I) at position 36 in the PR gene] (85.71%), H69K (85.71%), L89M (76.19%), K20R (57.14%), and G16E (47.62%), were detected in the PR genes (Table 1). 2020 Infectious disease reports Result HIV G16E;H69K;K20R;L89M;M36I 284;235;265;250;126 288;239;269;254;130 PR;PR 216;320 218;322 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. Two major mutations against NNRTIs, K103N and Y181C, were detected in peripheral blood samples derived from 2 patients, SS21 and SS41 (Table 1). 2020 Infectious disease reports Result HIV K103N;Y181C 36;46 41;51 NNRTI 28 34 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Also, the M16E mutants of the 5 strains of SIVcpzPtt Vifs degraded gA3F (S4 Fig). 2020 PLoS pathogens Result HIV M16E 10 14 Vif 53 57 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Although its mechanism(s) remain unclear, these data suggest that the E16M mutation of SIVgor Vif does not revert its ability to degrade gA3G. 2020 PLoS pathogens Result HIV E16M 70 74 Vif 94 97 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Although the WT Vif proteins of these SIVcpzPtt strains already weakly counteract gA3G, all M16E mutants tested in this experiment acquired the ability to efficiently trigger the degradation of gA3G (Fig 2J). 2020 PLoS pathogens Result HIV M16E 92 96 Vif 16 19 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. As shown in Fig 4C and S4 Fig, the Vif proteins including three strains of SIVgor (CP2139, CP684 and BPID2), five strains of SIVcpzPtt (MB897, CAM3, DP943, MT145 and LB7) and the M16E mutants of SIVcpzPtt Vif counteracted gA3F. 2020 PLoS pathogens Result HIV M16E 179 183 Vif;Vif;Capsid 35;205;143 38;208;145 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. As shown in S3 Fig, the ability of the E16M mutant to degrade gA3G seems to be lower than that of parental SIVgor Vif. 2020 PLoS pathogens Result HIV E16M 39 43 Vif 114 117 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Furthermore, the two basic residues at positions 15 and 19 are located on the same face of the alpha-helix, and the structural locations of these two basic residues are changed in the Vif proteins that are competent to counteract gA3G (SIVgor CP2139, SIVcpzPtt MB897 Vif M16E and M16D) (Fig 3D). 2020 PLoS pathogens Result HIV M16D;M16E 280;271 284;275 Vif;Vif 184;267 187;270 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. However, the level of gA3G in virions and viral infectivity of the E16M mutant were comparable to those of parental SIVgor Vif (S3 Fig). 2020 PLoS pathogens Result HIV E16M 67 71 Vif 123 126 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. In addition to the M16E mutant, the M16D mutant of MB897 Vif counteracted the gA3G-mediated antiviral effect, while the M16A and M16Q mutants did not (Fig 3A). 2020 PLoS pathogens Result HIV M16A;M16D;M16E;M16Q 120;36;19;129 124;40;23;133 Vif 57 60 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. In SupT11-CCR5-gA3G cells, however, the growth kinetics of the M16E mutant was significantly higher than those of WT and the E2X mutant (Fig 2H). 2020 PLoS pathogens Result HIV E2X;M16E 125;63 128;67 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. In the absence of A3s, infectivity of the M16E and E2X (vif-deleted) variants was comparable to that of wild-type (WT) virus (Fig 2E). 2020 PLoS pathogens Result HIV E2X;M16E 51;42 54;46 Vif 56 59 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Individual mutants were analyzed, and only M16E, but not the K6Q or D14P mutations, conferred the ability to counteract gA3G (Fig 2D). 2020 PLoS pathogens Result HIV D14P;K6Q;M16E 68;61;43 72;64;47 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. M16E enables SIVcpzPtt Vif to efficiently degrade gorilla A3G. 2020 PLoS pathogens Result HIV M16E 0 4 Vif 23 26 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. M16E, M16A, M16D, and M16Q). 2020 PLoS pathogens Result HIV M16A;M16D;M16Q;M16E 6;12;22;0 10;16;26;4 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Particularly, the topology of the two basic residues at positions 15 and 19 in the Vif proteins that are capable of counteracting gA3G was changed (i.e., SIVgor CP2139, SIVcpzPtt MB897 Vif M16E and M16D; Fig 3C). 2020 PLoS pathogens Result HIV M16D;M16E 198;189 202;193 Vif;Vif 83;185 86;188 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. These findings indicate that the acquisition of gA3G degradation activity through the M16E substitution is not limited to the Vif protein of SIVcpzPtt strain MB897 but generally shared across different SIVcpzPtt Vif proteins. 2020 PLoS pathogens Result HIV M16E 86 90 Vif;Vif 126;212 129;215 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. To address this, we constructed three additional mutants (M16A, M16D and M16Q). 2020 PLoS pathogens Result HIV M16A;M16D;M16Q 58;64;73 62;68;77 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. To analyze the effect of the M16E mutation on viral spread, we constructed IMCs of SIVcpzPtt MB897 expressing mutated (M16E) or no (E2X) Vif. 2020 PLoS pathogens Result HIV E2X;M16E;M16E 132;29;119 135;33;123 Vif 137 140 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. To assess whether the E16M reversion of SIVgor Vif renders it unable to counteract gA3G, we prepared the SIVgor CP2139 Vif E16M mutant. 2020 PLoS pathogens Result HIV E16M;E16M 22;123 26;127 Vif;Vif 47;119 50;122 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. To investigate whether M-to-E substitution confers broad gA3G neutralization activity to SIVcpzPtt Vif to counteract gA3G, we constructed the M16E mutants of four additional SIVcpzPtt strains. 2020 PLoS pathogens Result HIV M16E 142 146 Vif 99 102 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. D116 also showed more favorable interaction energy with the Mgbeta ion in the N155H variant ( 35 KJ/mol difference), while D64 showed no significant difference. 2020 Frontiers in molecular biosciences Result HIV N155H 78 83 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Except for replica 1 of the WT intasome, replica 1 of the N155H variant, and replicas 1 and 2 of the double mutant, all simulations reached equilibrium before 50 ns (Figure 2). 2020 Frontiers in molecular biosciences Result HIV N155H 58 63 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. In a study with crystals of the PFV IN soaked with INSTIs in a mutant equivalent to N155H,, the crystals made from mutant proteins soaked with inhibitors had only one Mn2+ (used instead of Mg2+ for crystallography purposes) in the active site. 2020 Frontiers in molecular biosciences Result HIV N155H 84 89 INSTI;IN 51;36 57;38 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. In the double mutant, the interaction between Mgbeta and residue 155 is also practically lost, while the interaction energy with E152 is increased by200 KJ/mol; but it did not show interactions between Mgbeta and D116 as favorable as the N155H mutant. 2020 Frontiers in molecular biosciences Result HIV N155H 238 243 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Indeed, in our simulations, the interaction between N155 and the terminal adenine is less favorable than the interaction between H155 and the nucleotide by23 KJ/mol in the N155H and25 KJ/mol in the double mutant, corroborating the previous calculations by close values. 2020 Frontiers in molecular biosciences Result HIV N155H 172 177 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. It is possible, however, that the addition of histidine in position 148 along with the mutation N155H destabilizes the coordination site beyond the minimum configuration required for catalysis. 2020 Frontiers in molecular biosciences Result HIV N155H 96 101 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Moreover, the adaptation of the E152 side chain to maintain the interaction with the Mgbeta changed the interaction energy of the pair from -404.7 KJ/mol (+-13.9) in the WT to -623.3 KJ/mol (+-17.9) in the N155H mutant. 2020 Frontiers in molecular biosciences Result HIV N155H 206 211 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. On the other hand, the region from residue 100-150 is much less mobile in both mutants, which is one possible explanation for the catalytic deficiency of the N155H; moreover, in chain C, the region around residue 155 is also less motile than the WT. 2020 Frontiers in molecular biosciences Result HIV N155H 158 163 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The double mutant displays huge differences in the interaction energy between D116 and Mgalpha ( 200 KJ/mol difference) when compared with WT and N155H; apart from this, all other catalytic residues interact with Mgalpha with very similar energy values in all systems. 2020 Frontiers in molecular biosciences Result HIV N155H 146 151 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The lack of conformational change in the terminal adenine of the N155H variant is consistent with predictions made by. 2020 Frontiers in molecular biosciences Result HIV N155H 65 70 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The lowest dope score models constructed for the cSSC of WT, N155H, and N155H+Q148H showed98% of the residues in the allowed and favored regions of the Ramachandran plot. 2020 Frontiers in molecular biosciences Result HIV N155H;N155H;Q148H 61;72;78 66;77;83 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The N1-N9 distances in N155H show slightly higher fluctuations than in N155H+Q148, but no opening event could be seen in neither mutant. 2020 Frontiers in molecular biosciences Result HIV N155H;N155H 23;71 28;76 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The position of the ions is tilted in relation to the WT coordinates in both mutants; however, in the double mutant, Mgbeta is shown closer to residue 155, while in N155H, the Mgbeta is coordinated much further from H155. 2020 Frontiers in molecular biosciences Result HIV N155H 165 170 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The presence of mutation Q148H seems to cause a peak in chain B exactly in the vicinity of the mutated residue. 2020 Frontiers in molecular biosciences Result HIV Q148H 25 30 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The T66I mutant could displace the ion through the introduction of an apolar and longer chain, and the T66K mutant could cause ion displacement through the introduction of a positively charged longer chain close to the divalent cation. 2020 Frontiers in molecular biosciences Result HIV T66I;T66K 4;103 8;107 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. This hypothesis is also supported by the fact that N155H and T66I have similar EC50 profiles. 2020 Frontiers in molecular biosciences Result HIV N155H;T66I 51;61 56;65 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. We believe that the resistance mechanisms of T66K and T66I could occur for similar events of ion displacement. 2020 Frontiers in molecular biosciences Result HIV T66I;T66K 54;45 58;49 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. When it comes to the dynamics of the ions, the distance between the two Mg2+ atoms increased in0.5 A on average in the N155H variant (Figure 6). 2020 Frontiers in molecular biosciences Result HIV N155H 119 124 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Identified TAMs were T215YF (n = 9), K219QE (n = 7), K70R (n = 7), D67N (n = 6), M41L (n = 4), and L210W (n = 3) (Table 3). 2020 PloS one Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 67;37;37;53;99;81;21;21 71;43;43;57;104;85;27;27 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. In general, thirteen samples (52%) had at least one thymidine analogue- resistance associated mutation (TAM) while three samples (12%) had T69D mutation together with at least 1 TAM. 2020 PloS one Result HIV T69D 139 143 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. M184V mutation was associated with high-level resistance to emtricitabine, and lamivudine; while K70R and D67N are among thymidine analogue-associated resistance mutations (TAM) reducing the susceptibility of all current NRTI in use. 2020 PloS one Result HIV D67N;K70R;M184V 106;97;0 110;101;5 NRTI 221 225 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. One participant (K38) who had previously used ritonavir-boosted lopinavir had L24I, L33F, I54V, and V82A mutations which together reduce the susceptibility of ritonavir-boosted lopinavir. 2020 PloS one Result HIV I54V;L24I;L33F;V82A 90;78;84;100 94;82;88;104 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Only M46I mutation was found in both samples. 2020 PloS one Result HIV M46I 5 9 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. The most frequent NNRTI resistance-associated mutations were K103N (44%), V106M (20%), and G190A (20%) (Fig 3), all of these three mutations confer high-level resistance to efavirenz and nevirapine. 2020 PloS one Result HIV G190A;K103N;V106M 91;61;74 96;66;79 NNRTI 18 23 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. The most frequent NRTI resistance-associated mutations were M184V (68%), K70R (28%), and D67N (24%) (Fig 4). 2020 PloS one Result HIV D67N;K70R;M184V 89;73;60 93;77;65 NRTI 18 22 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. The presence of T69D mutation along with at least 1 TAM reduces the susceptibility of all currently NRTIs in use. 2020 PloS one Result HIV T69D 16 20 NRTI 100 105 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. The same participant (K38) who was on ritonavir-boosted atazanavir at the date of interview had N88S mutation which confers a great effect on atazanavir. 2020 PloS one Result HIV N88S 96 100 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. Both CPR tool and IAS-USA algorithms were concordant in identifying five NNRTIs resistance-associated mutations: K103N in one patient (1.96%), Y188L, and H221Y in another patient (1.96%), K101E in one patient (1.96%), and V106A in another patient (1.96%). 2020 Retrovirology Result HIV H221Y;K101E;K103N;V106A;Y188L 154;188;113;222;143 159;193;118;227;148 NNRTI 73 79 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. G75S PDR mutation that confers low-level resistance to PI drug class atazanavir/ritonavir was observed in another study participant according to the CPR tool only (Table 2). 2020 Retrovirology Result HIV G75S 0 4 PI 55 57 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. However, L234I; which is detected in one individual (1.96%), was recognized by the CPR tool only (Table 2). 2020 Retrovirology Result HIV L234I 9 14 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. On the contrary, E138A mutation, which is associated with reduced RPV and ETR susceptibility, was detected by the IAS-USA mutation list only in two individuals (3.92%) (Table 2). 2020 Retrovirology Result HIV E138A 17 22 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. Single accessory resistance mutations and/or polymorphisms were present in over 15.6% (n = 8) of RT sequences with A98S (17.6%) and V179I (3.9%) being the most frequently observed mutations, while all PR sequences harbored at least two minor PIs resistance mutations and/or polymorphisms. 2020 Retrovirology Result HIV A98S;V179I 115;132 119;137 PI;PR;RT 242;201;97 245;203;99 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. The most frequent mutations observed in the PR sequence were H69K (100%) and M36L (98%), followed by L89M (58.8%), I15V (25.5%), K20R (25.5%), T74S (17.6%) and L89I (5.88%). 2020 Retrovirology Result HIV H69K;I15V;K20R;L89I;L89M;M36L;T74S 61;115;129;160;101;77;143 65;119;133;164;105;81;147 PR 44 46 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. Y115F and M184V PDR mutations that are recognized by both criteria, which confer limited resistance against NRTI drugs (abacavir, emtricitabine, lamivudine), were observed in one patient (1.96%) (Table 2). 2020 Retrovirology Result HIV M184V;Y115F 10;0 15;5 NRTI 108 112 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. One hundred patients with a documented M184V/I mutation were enrolled in this study. 2020 SAGE open medicine Result HIV M184I;M184V 39;39 46;46 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. One patient had a multidrug-resistant reverse transcriptase mutation present (Q151M) which conferred resistance to all available NRTIs. 2020 SAGE open medicine Result HIV Q151M 78 83 RT;NRTI 38;129 59;134 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The most commonly prescribed regimen among patients harboring only the M184V/I mutation (11/29 patients, 37.9%) was two NRTIs (one of which being 3TC or FTC) and an INSTI (either DTG or EVG) with a GSS of two. 2020 SAGE open medicine Result HIV M184I;M184V 71;71 78;78 INSTI;NRTI 165;120 170;125 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Twenty-nine patients (29%) harbored only the M184V/I mutation. 2020 SAGE open medicine Result HIV M184I;M184V 45;45 52;52 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. 3b), suggesting that cross-reactive T cells may have been elicited in the Pol S653K/Q-infected individuals. 2021 AIDS (London, England) Result HIV S653K;S653Q 78;78 85;85 Pol 74 77 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. 4b), supporting the idea that SL9-1K-specific T cells selected Pol S653L and S653T mutant viruses. 2021 AIDS (London, England) Result HIV S653L;S653T 67;77 72;82 Pol 63 66 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. 4d), suggesting that SL9-1K-specific T cells could select the Pol S653T/L mutant virus and the wild-type S virus. 2021 AIDS (London, England) Result HIV S653L;S653T 66;66 73;73 Pol 62 65 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. 5b), indicating that Pol S653A/T/L mutations impaired the ability of SL9-specific T cells to suppress HIV-1 replication in vivo. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 25;25;25 34;34;34 Pol 21 24 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Among 11 HLA-C*15:05+ individuals infected with Pol S653K/Q, the responders to SL9-1K or SL9-1Q peptide showed trends toward a higher CD4+ cell count than the nonresponders. 2021 AIDS (London, England) Result HIV S653K;S653Q 52;52 59;59 Pol 48 51 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Critical effect of S653A/T/L mutations on disease outcome via loss of HIV-1 suppression by T cells. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 19;19;19 28;28;28 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Effect of Pol S653A, S653T, and S653L mutations on SL9-specific T-cell recognition. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 14;32;21 19;37;26 Pol 10 13 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Five HLA-C*15:05-associated mutations (Pol S653A, Pol S653T, Pol S653L, Pol I655V, and Pol K657R) were found within SL9 epitope in Vietnamese individuals infected with the HIV-1 subtype A/E virus. 2021 AIDS (London, England) Result HIV I655V;K657R;S653A;S653L;S653T 76;91;43;65;54 81;96;48;70;59 Pol;Pol;Pol;Pol;Pol 39;50;61;72;87 42;53;64;75;90 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. However, we found only a small difference in replication capacity between S653A/T and wild-type virus. 2021 AIDS (London, England) Result HIV S653A;S653T 74;74 81;81 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Indeed, the T-cell responses to the mutant peptides were detected in five of the 11 individuals infected with Pol S653K/Q viruses: responses to the SL9-1K peptide were detected in three of the six Pol S653K-infected individuals, while those to SL9-1Q were found in two of the six Pol S653Q-infected individuals. 2021 AIDS (London, England) Result HIV S653K;S653K;S653Q;S653Q 201;114;284;114 206;121;289;121 Pol;Pol;Pol 110;197;280 113;200;283 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Longitudinal analysis on selection of Pol S653T/L viruses by SL9-1K-specific T cells in an HLA-C*15:05+ individual. 2021 AIDS (London, England) Result HIV S653L;S653T 42;42 49;49 Pol 38 41 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. No significant difference in CD4+ cell count or pVL was found between the individuals infected with wild-type virus and those with Pol S653A/T/L mutant viruses among a total of 312 HLA-C*15:05-negative individuals (data not shown). 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 135;135;135 144;144;144 Pol 131 134 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Over all, these results demonstrated that SL9-1K-specific T cells could select the Pol S653L/T mutant virus in this individual. 2021 AIDS (London, England) Result HIV S653L;S653T 87;87 94;94 Pol 83 86 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Recognition of Pol S653K/Q virus-infected cells by SL9-1K/1Q-specific T cells. 2021 AIDS (London, England) Result HIV S653K;S653Q 19;19 26;26 Pol 15 18 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. S2) was found between HLA-C*15:05+ individuals infected with the wild-type virus and those with the Pol I655V or Pol K657R virus. 2021 AIDS (London, England) Result HIV I655V;K657R 104;117 109;122 Pol;Pol 100;113 103;116 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. The individuals infected with the Pol S653A, Pol S653T, or Pol S653L virus had a higher pVL than those infected with the wild-type one, but no significant difference was found between wild-type and mutant groups. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 38;63;49 43;68;54 Pol;Pol;Pol 34;45;59 37;48;62 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. The individuals infected with the wild-type virus had a significantly higher CD4+ cell count than those infected with the Pol S653A or Pol S653T mutant virus and higher CD4+ cell count, but not significantly so, than the individuals infected with Pol S653L. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 126;251;139 131;256;144 Pol;Pol;Pol 122;135;247 125;138;250 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. The replication capacity of the Pol S653A mutant virus was higher than that of the wild-type virus, whereas that of the Pol S653T one was lower. 2021 AIDS (London, England) Result HIV S653A;S653T 36;124 41;129 Pol;Pol 32;120 35;123 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. These bulk T cells recognized the cells infected with the Pol S653A mutant virus much more weakly than those with the wild-type virus, whereas they failed to recognize the cells infected with the Pol S653T or Pol S653L mutant virus. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 62;213;200 67;218;205 Pol;Pol;Pol 58;196;209 61;199;212 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. To investigate the effects of Pol S653A/T/L mutations on SL9-specific T-cell recognition, we analyzed the recognition of the mutant epitope peptides by SL9-specific bulk T cells. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 34;34;34 43;43;43 Pol 30 33 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. We detected Pol S653K/S653Q mutations in 17 of 23 HLA-C*15:05+ individuals infected with mutants at Pol653 other than Pol S653A/T/L. 2021 AIDS (London, England) Result HIV S653A;S653K;S653L;S653Q;S653T 122;16;122;22;122 131;21;131;27;131 Pol;Pol;Pol 12;100;118 15;103;121 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. We detected T-cell responses to SL9 wild-type peptide in four of 11 Pol S653K/Q-infected individuals but in none of five Pol S653F/H/N/Y/I-infected ones. 2021 AIDS (London, England) Result HIV S653F;S653H;S653I;S653K;S653N;S653Q;S653Y 125;125;125;72;125;72;125 138;138;138;79;138;79;147 Pol;Pol 68;121 71;124 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. We finally clarified the effect of Pol S653A/T/L mutations on HIV-1 suppression by SL9-specific T cells in vivo. 2021 AIDS (London, England) Result HIV S653A;S653L;S653T 39;39;39 48;48;48 Pol 35 38 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. We first investigated the ability of T cells recognizing 1K/1Q epitopes to suppress HIV-1 replication in vivo, since they had abilities to recognize cells infected with Pol S653K/Q mutant viruses. 2021 AIDS (London, England) Result HIV S653K;S653Q 173;173 180;180 Pol 169 172 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. We next analyzed replication capacities of PolS653A/S653T/S653L mutant viruses in vitro. 2021 AIDS (London, England) Result HIV S653L;S653T 58;52 63;57 Pol 43 46 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. We therefore combined wild-type-infected responders to the wild-type peptide and Pol S653K/Q-infected responders to 1K/1Q ones and then compared the CD4+ cell count between these responders and the Pol S653A/T/L virus-infected responders to the wild-type peptide. 2021 AIDS (London, England) Result HIV S653A;S653K;S653L;S653Q;S653T 202;85;202;85;202 211;92;211;92;211 Pol;Pol 81;198 84;201 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. Of these, one had HIV-1 strain harbouring I84IT and the other had M46MI protease inhibitor (PI)-associated mutation in CSF but not in the plasma. 2020 Medicine Result HIV I84I;I84T;M46I;M46M 42;42;66;66 47;47;71;71 PR;PI 72;92 80;94 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. The most predominant mutation was K101E, occurring in HIV-1 strains of 2 plasma samples and in 1 CSF sample. 2020 Medicine Result HIV K101E 34 39 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. The third participant had HIV-1 strain with RT mutation K101E in plasma and V106 M in CSF. 2020 Medicine Result HIV K101E;V106M 56;76 61;82 RT 44 46 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Additionally, P90A was previously shown to activate innate immune signaling and interferon expression, but this activity was not connected to TRIM5. 2020 PLoS pathogens Result HIV P90A 14 18 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Expression of a dominant-negative kinase-dead mutant of TAK1 (K63W) did not activate, and in fact reduced, AP1 signaling. 2020 PLoS pathogens Result HIV K63W 62 66 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. For these experiments, MOI was determined in permissive TRIM5-null CrFK cells, and an equal CrFK MOI of WT and P90A virus was used. 2020 PLoS pathogens Result HIV P90A 111 115 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. For these studies, we used an HIV-1 mutant with a single amino acid substitution in the capsid protein (P90A) that was recently shown to be strongly restricted by human TRIM5 in primary immune cells. 2020 PLoS pathogens Result HIV P90A 104 108 Capsid 88 94 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Furthermore, chemical inhibition of the NF-kappaB and AP1 pathways, or of autophagy, with the compounds BAY11-7085, SP600125, and 3-methyladenine respectively attenuated the anti-HIV effect of P90A priming (Figs 7D and S4G). 2020 PLoS pathogens Result HIV P90A 193 197 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. However, an important caveat to these studies is that mutations of some residues found in LIR1, notably F187A, can disrupt TRIM5 self-assembly and retroviral restriction. 2020 PLoS pathogens Result HIV F187A 104 109 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. In the experiments described above, we saw that HIV-1 CA P90A induced the expression of antiviral interferon beta in an autophagy factor-dependent manner. 2020 PLoS pathogens Result HIV P90A 57 61 Capsid 54 56 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. In these experiments, TRIM5 knockout THP-1 cells expressed reduced IFNB1 under basal conditions and IFNB1 expression was not increased in response to HIV-1 CA P90A infection. 2020 PLoS pathogens Result HIV P90A 159 163 Capsid 156 158 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. The effect of priming correlated with the species-specific ability of TRIM5 to restrict the priming virus, as priming with an equal CrFK MOI of a WT capsid-bearing virus that was otherwise identical to HIV-1 CA P90A was significantly less efficient in restricting WT HIV-1 infection of THP1 cells (Figs 6E and S4C). 2020 PLoS pathogens Result HIV P90A 211 215 Capsid;Capsid 149;208 155;210 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. The results from these experiments were consistent with what we have reported above regarding the role of autophagy factors in TRIM5-dependent signaling: the effect of HIV-1 CA P90A priming was largely abrogated in autophagy factor knockout cells. 2020 PLoS pathogens Result HIV P90A 177 181 Capsid 174 176 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Together, these results are consistent with HIV-1 CA P90A infection stimulating TRIM5-dependent inflammatory gene expression. 2020 PLoS pathogens Result HIV P90A 53 57 Capsid 50 52 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Transduction efficiency of WT HIV was not impacted by TRIM5 knockout, and the WT virus was still slightly more infectious than P90A in the TRIM5 KO cells. 2020 PLoS pathogens Result HIV P90A 127 131 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. TRIM5-dependent STR is not specific to cell type, as P90A priming of the hepatoma cell line Huh7 protected those cells from transduction with WT HIV pseudovirus (S4E Fig). 2020 PLoS pathogens Result HIV P90A 53 57 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. We confirmed that the P90A virus is restricted by TRIM5 in THP-1 cells, as TRIM5 knockout increase P90A transduction efficiency by ~10 fold (Figs 5A and S3A). 2020 PLoS pathogens Result HIV P90A;P90A 22;99 26;103 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. We found that priming of THP-1 cells with either HIV-1 CA P90A (Figs 6B, 6C and S4A) or with N-MLV (Figs 6D and S4B) reduced the ability of TRIM5-resistant WT HIV-1 to infect THP-1 macrophages by 3-4 fold relative to what was seen in unprimed THP-1. 2020 PLoS pathogens Result HIV P90A 58 62 Capsid 55 57 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. We next generated ULK1, BECN1, and ATG7 THP-1 cell lines (S3D Fig) to test whether HIV-1 CA P90A infection could similarly induce the expression of pro-inflammatory genes in cells lacking autophagy. 2020 PLoS pathogens Result HIV P90A 92 96 Capsid 89 91 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. We next tested whether priming with HIV-1 CA P90A could attenuate WT HIV-1 infection in ULK1 and BECN1 knockout THP-1 cells. 2020 PLoS pathogens Result HIV P90A 45 49 Capsid 42 44 HIV infections 69 84 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. When THP-1 macrophages are exposed to equal MOI of WT or P90A HIV, only P90A induced the expression of IFNB1 mRNA (S3C Fig). 2020 PLoS pathogens Result HIV P90A;P90A 57;72 61;76 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Whereas infection of control THP-1 macrophages with HIV-1 CA P90A increases the expression of IFNB1, this effect is not seen in ULK1, BECN1, or ATG7 knockout THP-1 cells (Fig 5B). 2020 PLoS pathogens Result HIV P90A 61 65 Capsid 58 60 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Among all the eight Vpu variants (Vpu D68, Vpu85, Vpu E72, Vpu E75, Vpu 31, Vpu D72, Vpu 44, and Vpu D97), three of the variants having serine substitution (serine-52 and serine-56 conversion to isoleucine; S52I and S56I) had lost their functional beta-TrcP binding motif. 2020 BioResearch open access Result HIV S52I;S56I 207;216 211;220 Vpu;Vpu;Vpu;Vpu;Vpu;Vpu;Vpu;Vpu;Vpu 20;34;43;50;59;68;76;85;97 23;37;46;53;62;71;79;88;100 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Furthermore, to study the effect of S61P, S52I, and S56I mutations on the kinetic stability of Vpu variants, we performed the CHX chase assay. 2020 BioResearch open access Result HIV S52I;S56I;S61P 42;52;36 46;56;40 Vpu 95 98 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Interestingly, we noticed for the first time the genetic evidence for positive selection of Vpu variants showing substitution of a serine residue (serine-61 conversion to proline [S61P]) in four of our variants (Vpu D72, Vpu 44, Vpu D97, and Vpu 84). 2020 BioResearch open access Result HIV S61P 180 184 Vpu;Vpu;Vpu;Vpu;Vpu 92;212;221;229;242 95;215;224;232;245 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Notably, S61P variants. 2020 BioResearch open access Result HIV S61P 9 13 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. The kinetic stability of all the variants was comparable with the wild-type Vpu B except two variants (Vpu D72 and D97), with substitution of serine residue (S61P) showing no significant reduction in protein levels. 2020 BioResearch open access Result HIV S61P 158 162 Vpu;Vpu 76;103 79;106 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. We examined the functional implication of S61P natural mutation found in our variants with respect to intracellular stability and expression. 2020 BioResearch open access Result HIV S61P 42 46 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. All the point mutations were exposed to the surface of the pentameric capsomer except for Tyr79 , Thr47Ser, and Ile115Phe. 2020 International journal of molecular sciences Result HIV I115F;T47S 112;98 121;106 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Finally, A549 cells infected with 17 U sample, carrying Ile115Phe substitution, located in the VP1 beta-sandwich core, showed, at 3 d.p.i., a MCPyV viral load of 1 x 103 copies/cell and, at 7 d.p.i., of 1.2 x 103 copies/cell (Table 2). 2020 International journal of molecular sciences Result HIV I115F 56 65 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Finally, A549 cells infected with SPNT 7 P in which Asp69Val, Tyr79 , and Ser251Phe were detected, evidenced at 3 d.p.i., a viral load of 6.2 x 102 copies/cell and, at 7 d.p.i., of 1 x 103 copies/cell (Table 2). 2020 International journal of molecular sciences Result HIV D69V;S251F 52;74 60;83 Asp 52 55 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Finally, in MCPyV 17 U only the T to A transversion in 4085 nucleotide position was found (Figure 2), whereas in plasma sample (17 P) the I (ATATTGCCTCCCACATCTGCAATGTGTCACAGGTAATATCCT), previously described for 11 P between nucleotides 4127 and 4128, (Figure 3) and three double : a TG (4153-4154), a CA (4179-4180) and a GG (4246-4247) were revealed (Figure 3). 2020 International journal of molecular sciences Result HIV T4085A 32 59 Capsid 303 305 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. In detail, MCPyV 7 present in urine (7 U) contained the 4289 T to A transversion whereas, in plasma (7 P), a 4222 T to A transversion and a of a 3 bp (TAA) at nucleotide positions 4192-4194 were observed (Figure 2 and Figure 3). 2020 International journal of molecular sciences Result HIV T4222A;T4289A 109;56 120;67 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Infection using SPNT 17 U with Ile115Phe substitution, displayed a MCPyV load of 5.8x103 copies/cell at 3 d.p.i. 2020 International journal of molecular sciences Result HIV I115F 31 40 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Interestingly, the mutation Ile115Phe created an aromatic cluster of three Phe residues between the contact interface formed by the VP1 alpha-pentamer and the alpha', alpha'' monomers of the surrounding five capsomers (Figure 7). 2020 International journal of molecular sciences Result HIV I115F 28 37 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. of 2 x 103 copies/cell and, at 7 d.p.i., a MCPyV load of 3.5 x 103 copies/cell (Table 2) and in cells infected with SPNT 7 U, carrying a VP1 characterized by Thr47Ser. 2020 International journal of molecular sciences Result HIV T47S 158 166 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. PROVEAN server predicted that the substitutions Asp69Val, Ser251Phe and Ile115Phe caused a neutral effect, whereas the mutations Thr47Ser and Tyr79 produced a deleterious effect (Table 1). 2020 International journal of molecular sciences Result HIV D69V;I115F;S251F;T47S 48;72;58;129 56;81;67;137 Asp 48 51 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Regarding the amino-acid analysis of the remaining samples (7 P and 11 P), 7 P revealed, within the first neutralizing epitope loop, the substitution Asp69Val, the Tyr79 and, located in the apical loop, the Ser251Phe change (Figure 5a,b and Figure 6). 2020 International journal of molecular sciences Result HIV D69V;S251F 150;208 158;217 Asp 150 153 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Seven out of 34 samples (7 P, 11 P, 12 P and 17 P; 7 U, 12 U and 17 U) revealed, in two urine (7 U and 17 U), a VP1 characterized by Thr47Ser and Ile115Phe substitutions, sited in the VP1 N-terminus and in the beta-sandwich core, respectively (Figure 4 and Figure 5a,b). 2020 International journal of molecular sciences Result HIV I115F;T47S 146;133 155;141 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Specifically, A549 cells infected with 7 U sample carrying MCPyV VP1 characterized by Thr47Ser mutation, showed, at 3 d.p.i., a MCPyV viral load of 5 x 102 copies/cell and, at 7 d.p.i., a MCPyV viral load of 9.2 x 102 copies/cell (Table 2). 2020 International journal of molecular sciences Result HIV T47S 86 94 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. The analysis conducted by DynaMut server predicted that the mutations Asp69Val, Ser251Phe and Ile115Phe stabilized the structure of VP1, whereas the mutation Thr47Ser reduced the VP1 stability (Table 1). 2020 International journal of molecular sciences Result HIV D69V;I115F;S251F;T47S 70;94;80;158 78;103;89;166 Asp 70 73 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. The MCPyV replication in A549 cells infected with plasma samples was observed only in cells infected with 7 P, despite the presence of Asp69Val, Tyr79 and Ser251Phe. 2020 International journal of molecular sciences Result HIV D69V;S251F 135;156 143;165 Asp 135 138 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Thr47Ser and Ile115Phe mutations were in a loop exposed to the internal virus capsid surface and at the interface between capsomers, respectively. 2020 International journal of molecular sciences Result HIV I115F;T47S 13;0 22;8 Capsid 78 84 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. As it turned out, a minor V106M mutation with a frequency of 4.30% was found by NGS platform in patient M but not identified by SBS method. 2020 Infection and drug resistance Result HIV V106M 26 31 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Both of them were subtype B and had no resistance mutation to NRTIs, protease inhibitors or integrase inhibitors, but had a common V106I mutation. 2020 Infection and drug resistance Result HIV V106I 131 136 IN;PR;NRTI 92;69;62 101;77;67 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. However, for patient M, V106M alone is associated with a high-level reduction in NVP (60) and EFV (60) susceptibility as well as an intermediate reduction in DOR (50) susceptibility, while together with V106I, especially K101E and K103N, the mutation scores are increased to 65, 135, 25, 150 and 55 for DOR, EFV, ETR, NVP and RPV. 2020 Infection and drug resistance Result HIV K101E;K103N;V106I;V106M 221;231;203;24 226;236;208;29 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. In addition to the transmitted drug resistance of V106I mutation, she acquired K101E and K103N mutations with mutant frequency of 41.03% and 27.56%, respectively. 2020 Infection and drug resistance Result HIV K101E;K103N;V106I 79;89;50 84;94;55 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Patient F also had an E138A mutation. 2020 Infection and drug resistance Result HIV E138A 22 27 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Patient I was firstly performed DRM testing using SBS method on October 14 before starting ART and was found to be subtype B infection and V106I mutation (Table 1). 2020 Infection and drug resistance Result HIV V106I 139 144 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Patient M Acquired K101E, K103N and Minor Mutation of V106M After Improperly Discontinuing Antiretroviral Drugs. 2020 Infection and drug resistance Result HIV K101E;K103N;V106M 19;26;54 24;31;59 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Subsequently, the DRMs were confirmed using Vela NGS method and the mutant frequency of V106I for three patients were 99.73% (Patient I), 95.38% (Patient M) and 99.57% (Patient F), respectively. 2020 Infection and drug resistance Result HIV V106I 88 93 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Surprisingly, the homologous strain itself had V106I mutation according to the Stanford HIV-1 drug resistance database. 2020 Infection and drug resistance Result HIV V106I 47 52 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. The mutant frequency of E138A was 67.78% and was not transmitted to patient M. 2020 Infection and drug resistance Result HIV E138A 24 29 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Three Patients Had a Common Transmitted Mutation of V106I. 2020 Infection and drug resistance Result HIV V106I 52 57 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. V106I mutation shows susceptible to EFV (0), and potential low-level resistance to doravirine (DOR, 10), etravirine (ETR, 10), nevirapine (NVP,10) and rilpivirine (RPV, 10), which increases to low-level resistance to ETR (20) and RPV (25) when E138A is also present. 2020 Infection and drug resistance Result HIV E138A;V106I 244;0 249;5 33136738 High Prevalence of HIV-1 Drug Resistance and Dynamics of Transmission Among High-Risk Populations in Port-au-Prince, Haiti. Five clusters had shared resistance mutations, and K103N (14/24) and M184V (12/24) were the main DRM shared. 2020 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;M184V 51;69 56;74 33136738 High Prevalence of HIV-1 Drug Resistance and Dynamics of Transmission Among High-Risk Populations in Port-au-Prince, Haiti. Of the DRM, K103N (46/119; 38.6%), which causes high-level resistance to efavirenz and nevirapine, and M184V (35/119; 29.4%), associated with TDF and Emtricitabine (FTC) resistance, were the most frequently observed. 2020 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;M184V 12;103 17;108 33136738 High Prevalence of HIV-1 Drug Resistance and Dynamics of Transmission Among High-Risk Populations in Port-au-Prince, Haiti. Resistance mutations were detected in 1 of the 5 individuals classified as recently infected (NNRTI: K103N; K101E). 2020 Journal of acquired immune deficiency syndromes (1999) Result HIV K101E;K103N 108;101 113;106 NNRTI 94 99 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. 6), with the resistant clones from VF1 and VF2 clustering together and sharing the 4-amino-acid resistance-associated signature S126del/H127del/T122A/G123E. 2020 mBio Result HIV G123E;T122A 150;144 155;149 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. A combination of S126del, H127del, and the T122A and G123E mutations in the susceptible virus led to a 4-fold decrease in susceptibility to LPV (FC in IC50 from 5.3 to 22.7). 2020 mBio Result HIV G123E;H127del;S126del;T122A 53;26;17;43 58;33;24;48 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Baseline genotype (pre-PI) indicated that the individual had developed extensive resistance to first-line ART, with the nucleoside reverse transcriptase inhibitor (NRTI) mutations K65R and M184I conferring high-level tenofovir and lamivudine resistance, respectively, as well as K103N and Y181C conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI). 2020 mBio Result HIV K103N;K65R;M184I;Y181C 279;180;189;289 284;184;194;294 NNRTI;NRTI;NNRTI;NRTI;PI 320;120;368;164;23 355;152;373;168;25 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Conversely, S126ins, H127ins, and the A122T and E123G substitutions in the LPV-resistant virus led to a 3-fold decrease in resistance. 2020 mBio Result HIV A122T;E123G;H127ins;S126ins 38;48;21;12 43;53;28;19 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. In protease, there was an M46V mutation in the resistant virus that was found to have no impact on LPV susceptibility. 2020 mBio Result HIV M46V 26 30 PR 3 11 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. None of the four gag-pro clones from baseline (before initiation of PI) contained any of the four amino acid changes (T122A, G123E, S126del, and H127del), consistent with NGS data showing that these variants were present at <5% (Table 2). 2020 mBio Result HIV G123E;H127del;S126del;T122A 125;145;132;118 130;152;139;123 Gag;PI 17;68 20;70 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Of note, we observed loss of mutations affecting susceptibility to lamivudine (M184I), tenofovir (K65R), and efavirenz (K103N) between baseline and VF1. 2020 mBio Result HIV K103N;K65R;M184I 120;98;79 125;102;84 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Results of the phenotypic drug susceptibility testing of these mutants showed that only E123G appeared to increase susceptibility. 2020 mBio Result HIV E123G 88 93 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. The five mutations (T122A/G123E/S126del/H127del/V128del) reduced susceptibility to LPV more than 3-fold, indicating that they are effective in a divergent subtype. 2020 mBio Result HIV G123E;T122A 26;20 31;25 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. The matrix deletions of S126 and H127 act synergistically with T122A and G123E in Gag. 2020 mBio Result HIV G123E;T122A 73;63 78;68 Matrix;Gag 4;82 10;85 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. The NGS showed that T122A and G123E were present at low abundance before initiation of PI (approximately 5% of reads) (Table 2). 2020 mBio Result HIV G123E;T122A 30;20 35;25 PI 87 89 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. The proportion of T122A/G123E increased at VF1 to 13%. 2020 mBio Result HIV G123E;T122A 24;18 29;23 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. These mutations were observed at increased frequency at VF2 both by target-enriched NGS and also direct gag-pro PCR from plasma, but NGS also showed emergence of the lamivudine resistance mutation M184V, suggesting improved adherence to the lamivudine regimen between VF1 and VF2. 2020 mBio Result HIV M184V 197 202 Gag 104 107 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Using the resistant viral clone, four different mutant viruses were created with single amino acid changes in Gag: A122T, E123G, S126ins, and H127ins. 2020 mBio Result HIV A122T;E123G;H127ins;S126ins 115;122;142;129 120;127;149;136 Gag 110 113 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. We chose the reference p8.9NSX subtype B virus and made the amino acid deletions at Gag positions 126 and 127 as well as the adjacent T122A and G123E mutations. 2020 mBio Result HIV G123E;T122A 144;134 149;139 Gag 84 87 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. We next tested whether the four-amino-acid signature T122A/G123E/S126del/H127del could confer LPV resistance in a different subtype context. 2020 mBio Result HIV G123E;T122A 59;53 64;58 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. We noted that the more resistant virus had a deletion of Gag positions 126 and 127 as well as adjacent T122A and G123E mutations. 2020 mBio Result HIV G123E;T122A 113;103 118;108 Gag 57 60 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Finally, to validate the effects of the Y120F/Q125H mutations on Nef function in the context of patient-derived Nef sequences, we reverted each Nef clone to the consensus Y120 and Q125 to generate paired mutant/revertant constructs. 2020 Scientific reports Result HIV Q125H;Y120F 46;40 51;45 Nef;Nef;Nef 65;112;144 68;115;147 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. HIV-NefY120F/Q125H exhibited a substantial increase in p24 Gag antigen, but the peak level reached at Day 9 was significantly reduced compared to that of HIV-NefSF2 in PBMC from both donors (p < 0.03. 2020 Scientific reports Result HIV Q125H 13 18 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. In 6 patients, all sequenced clones had both Y120F/Q125H mutations; whereas in the other patients, a minority of the Nef clones had the single Y120F mutation. 2020 Scientific reports Result HIV Q125H;Y120F;Y120F 51;45;143 56;50;148 Nef 117 120 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. indicating that the Nef Y120F and Q125H mutations in combination impaired viral replication. 2020 Scientific reports Result HIV Q125H;Y120F 34;24 39;29 Nef 20 23 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. NefY120F/Q125H exhibited a substantial increase in infectivity, but ~ 20% reduced level compared to HIV-NefSF2 regardless of the amount of inocula used (p < 0.04. 2020 Scientific reports Result HIV Q125H;Y120F 9;3 14;8 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Next, by the use of a transfection-based assay, 2 or 3 Nef sequences harboring the Y120F/Q125H mutations were tested for Nef's ability to downregulate SERINC5 from the cell surface. 2020 Scientific reports Result HIV Q125H;Y120F 89;83 94;88 Nef;Nef 55;121 58;124 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. No substantial effects were observed with the single mutations; whereas the double Y120F/Q125H mutation showed ~ 20% reduced ability to counteract SERINC3/5. 2020 Scientific reports Result HIV Q125H;Y120F 89;83 94;88 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Rather, because F121 and D123 are highly conserved residues important for certain Nef functions, these results suggest that modulation of pVL may be attributable to altered Nef functions mediated by the HLA-adapted Nef Y120F and Q125H variants. 2020 Scientific reports Result HIV Q125H;Y120F 229;219 234;224 Nef;Nef;Nef 82;173;215 85;176;218 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. So we wanted to examine whether the Y120F and Q125H mutations would impair the ability of Nef to counteract SERINC3/5. 2020 Scientific reports Result HIV Q125H;Y120F 46;36 51;41 Nef 90 93 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Testing of the F121A and D123A mutations in NefSF2 showed nearly complete disruption of Nef's ability to counteract SERINC3/5. 2020 Scientific reports Result HIV D123A;F121A 25;15 30;20 Nef 88 91 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. The data demonstrated that the peak level of p24 Gag antigen of HIV-NefY120F/Q125H was significantly lower than that of NefSF2 (Wilcoxon matched-pairs test, p = 0.0313. 2020 Scientific reports Result HIV Q125H;Y120F 77;71 82;76 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. The observed difference in Nef's ability to stimulate viral replication could be attributed by viral infectivity of the viral inocula used, because Nef is known to enhance virion infectivity and the Y120F and Q125H mutations may affect this Nef's function. 2020 Scientific reports Result HIV Q125H;Y120F 209;199 214;204 Nef;Nef;Nef 27;148;241 30;151;244 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. These results indicate that the HLA-B*51:01-adapted Y120F/Q125H mutations selectively impaired Nef's ability to counteract SERINC3/5 but that CD4, CCR5, CXCR4 and HLA downregulation functions and CD74 upregulation function remained unaffected. 2020 Scientific reports Result HIV Q125H;Y120F 58;52 63;57 Nef 95 98 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. We first analyzed the sequence of amplified nef gene fragments after they had been cloned into a plasmid (average of 8 clones per subject) in 10 out of 12 HLA-B*51:01+ patients whose autologous viruses had the Y120F/Q125H mutations. 2020 Scientific reports Result HIV Q125H;Y120F 216;210 221;215 Nef 44 47 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. We first tested whether the Y120F and Q125H mutations in Nef impaired viral replication capacity in primary CD4+ cells. 2020 Scientific reports Result HIV Q125H;Y120F 38;28 43;33 Nef 57 60 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. We prepared PBMC from 2 HIV-negative donors, exposed them to HIV-NefSF2, HIV Nef or HIV-NefY120F/Q125H at Day 0, and measured time-course changes in p24 Gag antigen secreted into the culture supernatant (as a measure of viral replication) until Day15. 2020 Scientific reports Result HIV Q125H 97 102 p24;Nef;Nef;Gag 149;77;88;153 152;80;91;156 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. We then tested the NefSF2 harboring the Y120F, Q125H, and Y120F/Q125H mutations for SERINC3/5 counteraction. 2020 Scientific reports Result HIV Q125H;Q125H;Y120F;Y120F 47;64;40;58 52;69;45;63 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. In addition, the accessory protease mutations K20R, L10I, I13V, and G16E were detected. 2020 Viruses Result HIV G16E;I13V;K20R;L10I 68;58;46;52 72;62;50;56 PR 27 35 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. In addition, the prior M184V mutation:but no other NRTI mutations:was detected at a frequency of 100%. 2020 Viruses Result HIV M184V 23 28 NRTI 51 55 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. In the fifth cycle, six time-points were measured, and one of them was positive for the M184V mutation at a low frequency of 0.9% (Figure 1). 2020 Viruses Result HIV M184V 88 93 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Longitudinal blood samples were analyzed using an in-house allele-specific-PCR (AS-PCR) to determine the frequency of M184V and L90M drug-resistant variants. 2020 Viruses Result HIV L90M;M184V 128;118 132;123 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. The genotypic resistance test using Sanger technology revealed the M184I mutation causing high- and low-level resistance to 3TC/FTC and ABC, respectively. 2020 Viruses Result HIV M184I 67 72 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. The M184V mutation was not detectable in the second structured treatment interruption cycle. 2020 Viruses Result HIV M184V 4 9 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. The M184V mutation, which was identified during the SSITT trial, was not present in 1997, suggesting a selection of the M184V mutation during the structured treatment interruption cycles (Figure 1). 2020 Viruses Result HIV M184V;M184V 4;120 9;125 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. This resistance test newly revealed the E138K, Q148R, and R263K INSTI mutations at frequencies of 100% by means of next-generation sequencing (NGS), causing high-level resistance to RAL, EVG, DTG, and BIC. 2020 Viruses Result HIV E138K;Q148R;R263K 40;47;58 45;52;63 INSTI 64 69 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. This resistance test revealed infection with HIV-1 subtype B and the presence of the accessory mutations M36I, I62V, and V77I not causing any clinically relevant resistance to antiretroviral drugs. 2020 Viruses Result HIV I62V;M36I;V77I 111;105;121 115;109;125 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Among the observed resistance mutations, 4/57 (7.0%) had conferring resistance to PI, other detected mutations were (L10F + V82Y), L10FV, L33LF, and L89LMV. 2020 Medicine Result HIV L10F;L10F;L10V;L33F;L33L;L89L;L89M;L89V;V82Y 117;131;131;138;138;149;149;149;124 122;136;136;143;143;155;155;155;128 PI 82 84 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Five patients had the same resistance mutations to NRTI (M184 V), these patients had different genotypes (B, C, and G), and this mutation is associated with resistance to the antiretroviral drugs: Lamivudine (3TC), Abacavir (ABC), and Emtricitabine (FTC). 2020 Medicine Result HIV M184V 57 63 NRTI 51 55 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Four patients had mutations in the protease region with no association to drug resistance (L33LF, L89LMV, L10FV, and [L10F + V82Y]), these patients were genotype C. 2020 Medicine Result HIV L10F;L10F;L10V;L33F;L33L;L89L;L89M;L89V;V82Y 106;118;106;91;91;98;98;98;125 111;122;111;96;96;104;104;104;129 PR 35 43 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. One patient had multi-drug mutation; the mutations (V82A + I84IV) and (L10F + Q58E) were found in the protease region while mutation M184 V was found to confer resistance to NRTI drugs. 2020 Medicine Result HIV I84I;I84V;L10F;M184V;Q58E;V82A 59;59;71;133;78;52 64;64;76;139;82;57 PR;NRTI 102;174 110;178 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. One patient had multiple resistance mutations to PI (V82A + I84IV, L01F + Q58E), and M184 V mutation to NRTI, he was genotype C and had resistance to the antiretroviral drugs: Atazanavir (ATV), Darunavir (DRV), Lopinavir (LPV), 3TC, ABC, and FTC. 2020 Medicine Result HIV I84I;I84V;L01F;M184V;Q58E;V82A 60;60;67;85;74;53 65;65;71;91;78;58 NRTI;PI 104;49 108;51 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Only one resistance mutation to NRTI was detected (M184 V) in 5/57 (8.8%). 2020 Medicine Result HIV M184V 51 57 NRTI 32 36 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Resistance mutations to NNRTI were detected in 3/57 (5.3%), these mutations were V179VD, V106I, and E138A. 2020 Medicine Result HIV E138A;V106I;V179D;V179V 100;89;81;81 105;94;87;87 NNRTI 24 29 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The patient with V106I mutation was genotype CRF01-AE, and had resistance to the antiretroviral drugs, ETR, NVP, and RPV, the patient with E138A mutation, was genotype B and had resistance to two antiretroviral drugs: ETR, and RPV. 2020 Medicine Result HIV E138A;V106I 139;17 144;22 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The patient with V179VD mutation was genotype C and had resistance to the antiretroviral drugs: Efavirenz (EFV), Etravirine (ETR), Nevirapine (NVP), and Rilpivirine (RPV). 2020 Medicine Result HIV V179D;V179V 17;17 23;23 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Three patients had resistance mutations to NNRTI (V179VD, V106I, and E138A). 2020 Medicine Result HIV E138A;V106I;V179D;V179V 69;58;50;50 74;63;56;56 NNRTI 43 48 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. The mutations were T97A (0.12%, 1/827), A128T (0.24%, 2/827), E157Q (0.85%, 7/827), and G163R (0.24%, 2/827). 2020 Infection and drug resistance Result HIV A128T;E157Q;G163R;T97A 40;62;88;19 45;67;93;23 33324386 Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. Among HPV81 MI, one of the seven patients (Pt422) showed an amino-acid substitution within the BC loop (N75Q), while five of the seven patients showed an amino-acid substitution in the FGb loop (T315N); no mutations were observed in HPV81 SI. 2020 Frontiers in microbiology Result HIV N75Q;T315N 104;195 108;200 33324386 Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. Only Pt807 with a I425V substitution at the COOH carboxyterminal had a weak increase in beta-turn coefficient (Supplementary Table 1). 2020 Frontiers in microbiology Result HIV I425V 18 23 33324386 Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. The G7332A (R520K) and A7334T (T521S) changes were observed in all of the strains, and thus they can be considered as polymorphisms. 2020 Frontiers in microbiology Result HIV A7334T;G7332A;R520K;T521S 23;4;12;31 29;10;17;36 33324386 Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. The RG-1 epitope, which encompasses residues 15-34 in L2 HPV81, showed a high degree of conservation, and only Pt211 showed the I34V substitution. 2020 Frontiers in microbiology Result HIV I34V 128 132 33324386 Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. The substitution of A350T was observed only in MI, whereas S346P was found only in two HPV81 strains of SI. 2020 Frontiers in microbiology Result HIV A350T;S346P 20;59 25;64 33347449 The genotype distribution, infection stage and drug resistance mutation profile of human immunodeficiency virus-1 among the infected blood donors from five Chinese blood centers, 2014-2017. 2) Seven nucleotide reverse transcriptase inhibitors (NRTIs) were: D67N (n = 4), M184L (n = 1), K70Q (n = 1), K219R (n = 1). 2020 PloS one Result HIV D67N;K219R;K70Q;M184L 67;110;96;81 71;115;100;86 RT;NRTI 20;54 41;59 33347449 The genotype distribution, infection stage and drug resistance mutation profile of human immunodeficiency virus-1 among the infected blood donors from five Chinese blood centers, 2014-2017. 3) Nine protease inhibitor (PIs) DRMs were observed including, seven PIs accessory DRMs: Q58E (n = 5), L23I (n = 1), I84M (n = 1) and two PIs major DRM: M46L (n = 2). 2020 PloS one Result HIV I84M;L23I;M46L;Q58E 117;103;153;89 121;107;157;93 PR;PI;PI;PI 8;28;69;138 16;31;72;141 33347449 The genotype distribution, infection stage and drug resistance mutation profile of human immunodeficiency virus-1 among the infected blood donors from five Chinese blood centers, 2014-2017. We analyzed the following specific DRMs: 1) 66.7% (32/48) DRMs were on nonnucleoside reverse transcriptase inhibitors (NNRTIs) as: V179E (n = 12), E138A (n = 4), Y188D (n = 1), K103N (n = 2), A98G (n = 1), K238N (n = 2), V179D (n = 8), E138G (n = 1), G190E (n = 1). 2020 PloS one Result HIV A98G;E138A;E138G;G190E;K103N;K238N;V179D;V179E;Y188D 192;147;236;251;177;206;221;131;162 196;152;241;256;182;211;226;136;167 NNRTI;NNRTI 71;119 106;125 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. Among the 38 patients who had both sanger sequencing and Illumina NGS data, 5% (2/38) had NRTI/NNRTI/PI resistance and none had INSTI resistance (one had an L74V substitution) by sanger sequencing however Illumina NGS for INSTI resistance detected four more INSTI resistance ( 1%) associated mutations with low frequency (G163R 3.25%, S153Y 1.36%, S153F 3.21% and Y143H 2.06%) (Table 5). 2020 Infection and drug resistance Result HIV G163R;L74V;S153F;S153Y;Y143H 322;157;348;335;364 328;161;353;340;369 INSTI;INSTI;INSTI;NNRTI;NRTI;PI 128;222;258;95;90;101 133;227;263;100;94;103 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. However, they have different mutation percentage and position in the NGS data (sample19: L74M (0.47%); sample31: L74M (0.51%) and 92G (0.49%)). 2020 Infection and drug resistance Result HIV L74M;L74M 89;113 93;117 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. The most common INSTI RAMs were G163K (0.4%) and E138A (0.4%) (Figure 3). 2020 Infection and drug resistance Result HIV E138A;G163K 49;32 54;37 INSTI 16 21 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. The most common RAMs to NRTIs were M184V and K65R (1.3%), while those for NNRTIs were V179D (4.5%), V106I (2.7%), and K103N (1.3%), and those for PIs were L10I (13.4%), A71T (5.8%), and L10V (4.0%). 2020 Infection and drug resistance Result HIV A71T;K103N;K65R;L10I;L10V;M184V;V106I;V179D 169;118;45;155;186;35;100;86 173;123;49;159;190;40;105;91 NNRTI;NRTI;PI 74;24;146 80;29;149 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. Two patients with S153F and S153Y low frequencies mutations started INSTI-based highly active antiretroviral therapy and none had virological failure by week 48. 2020 Infection and drug resistance Result HIV S153F;S153Y 18;28 23;33 INSTI 68 73 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. All individual INSTI DRMs were observed below the 20% threshold, with the exception of G140S (detected at the 25% level, sample from Spain collected in 2012) and G140A (21%, sample from Peru in 2011). 2021 HIV medicine Result HIV G140A;G140S 162;87 167;92 INSTI 15 20 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Conversely, resistance to efavirenz is mainly predicted by the K103NS mutations. 2021 HIV medicine Result HIV K103N;K103S 63;63 69;69 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Estimates of PI TDR are strongly influenced by the M46IL mutation, which was observed in 5.5% of all samples, mostly as low-level variants (Table 3). 2021 HIV medicine Result HIV M46I;M46L 51;51 56;56 PI 13 15 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Excluding M46IL variants would reduce estimated PI TDR (at the 2% threshold) from 11.4% to 6.6%. 2021 HIV medicine Result HIV M46I;M46L 10;10 15;15 PI 48 50 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Finally, the frequency of tenofovir resistance was estimated to be 1.3% at the 20% threshold, 1.6% at the 5% threshold, and 2.4% at the 2% threshold, despite the complete absence of the K65R mutation. 2021 HIV medicine Result HIV K65R 186 190 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. For example, K103NS was the most common NNRTI mutation in the USA and Latin America, whereas G190ASE was the most common NNRTI mutation in Europe, Africa and Asia. 2021 HIV medicine Result HIV G190A;G190E;G190S;K103N;K103S 93;93;93;13;13 100;100;100;19;19 NNRTI;NNRTI 40;121 45;126 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. K103NS variants were mainly observed (60/77, 78%) in > 80% of the viral quasispecies, E138K mainly (20/34, 59%) in < 5%, and G190ASE displayed a more uniform spread. 2021 HIV medicine Result HIV E138K;G190A;G190E;G190S;K103N;K103S 86;125;125;125;0;0 91;132;132;132;6;6 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. M184V and M184I were detected in seven and 18 samples respectively, the latter generally as a low-level variant (2-5%). 2021 HIV medicine Result HIV M184I;M184V 10;0 15;5 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Notably, the K65R mutation was not observed in any sample, even at the 2% threshold. 2021 HIV medicine Result HIV K65R 13 17 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. occurring in > 80% of the viral population), whereas a wider range of variant frequency was observed for K219QENR. 2021 HIV medicine Result HIV K219E;K219N;K219Q;K219R 105;105;105;105 113;113;113;113 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The D30N mutation was mainly (41/46, 89%) present as a low-level variant below 20%, whereas most (12/18, 67%) L90M were detected in > 80% of the viral quasispecies. 2021 HIV medicine Result HIV L90M;D30N 110;4 114;8 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The most common NNRTI DRMs - K103NS (3.5%), G190ASE (3.1%), and E138K (1.6%) - showed diverse patterns. 2021 HIV medicine Result HIV E138K;G190A;G190E;G190S;K103N;K103S 64;44;44;44;29;29 69;51;51;51;35;35 NNRTI 16 21 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The most common NRTI DRMs were T215 revertants (2.5%), M41L (2.2%), and K219QENR (1.7%). 2021 HIV medicine Result HIV K219E;K219N;K219Q;K219R;M41L 72;72;72;72;55 80;80;80;80;59 NRTI 16 20 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The T215 revertants and, to a lesser extent, M41L were mostly high-level variants representing the majority of the quasispecies. 2021 HIV medicine Result HIV M41L 45 49 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. 5D), which was absent from the top three clusters extracted from simulations with neutral H219 and H219Q mutant, as well as the ensemble of wild type CA structures solved by Manman et al. 2021 Computational and structural biotechnology journal Result HIV H219Q 99 104 Capsid 150 152 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Both of these analyses of CypA-bound CA simulations suggest that the H219Q mutation may potentially weaken CypA binding to the CA domain. 2021 Computational and structural biotechnology journal Result HIV H219Q 69 74 Capsid;Capsid 37;127 39;129 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Four of the mutations in the MA domain map onto the plasma membrane associating surface of our model, and three mutations - E12K, E40K and L75R - involve a switch to basic amino acids. 2021 Computational and structural biotechnology journal Result HIV E12K;E40K;L75R 124;130;139 128;134;143 Matrix 29 31 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Given the change in the overall size and charge of the residue in the WT and mutants (from small and neutral to large and acidic), the G123E mutation alters the accessibility and electrostatic properties in the vicinity of the cleavage site and would therefore be expected to directly interfere with proteolysis. 2021 Computational and structural biotechnology journal Result HIV G123E 135 140 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. In the H219Q mutant, the contacts made by the glutamine residue followed a largely similar pattern, although the frequency of interactions was noticeably lower compared to both neutral and protonated histidine. 2021 Computational and structural biotechnology journal Result HIV H219Q 7 12 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Interestingly, this loop houses H219Q, a mutation found in all seven variants from Gatanaga et al. 2021 Computational and structural biotechnology journal Result HIV H219Q 32 37 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. More importantly, the E40K and L75R mutations, which map around the interface of the MA trimer subunits, formed novel binding sites for PIP2 lipids. 2021 Computational and structural biotechnology journal Result HIV E40K;L75R 22;31 26;35 Matrix;PI 85;136 87;138 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. No noticeable difference was found between the flexibility of this loop in simulations with the neutral H219 versus the H219Q mutant. 2021 Computational and structural biotechnology journal Result HIV H219Q 120 125 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Taken together, the H219Q mutation on the CypA-binding loop may play a crucial role in fine-tuning CypA interactions, especially in low endosomal pH and CypA-enriched infected target cells. 2021 Computational and structural biotechnology journal Result HIV H219Q 20 25 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. The frequency of such interactions, however, was notably lower than that displayed by G123E, and interestingly, the mutation to glutamine resulted in a reduced contact with the cleavage site. 2021 Computational and structural biotechnology journal Result HIV G123E 86 91 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. To investigate the potential effects of the H219Q mutation upon CypA binding affinity, we performed two independent 500 ns atomistic MD simulations of a mature CA hexamer with each of the subunits bound to a CypA molecule. 2021 Computational and structural biotechnology journal Result HIV H219Q 44 49 Capsid 160 162 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. To investigate the potential role of this mutation vis-a-vis CA-CypA interactions, we performed two independent 500 ns atomistic MD simulations of the WT and H219Q mutant of the mature CA hexamer either in its CypA-free (apo) or CypA-bound state (Simulations 7-12 in Table S2). 2021 Computational and structural biotechnology journal Result HIV H219Q 158 163 Capsid;Capsid 61;185 63;187 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. To test this hypothesis, we performed two repeat 500 ns atomistic simulations of mature CA for the WT and Q199H variants, the latter in either protonated or unprotonated states (Simulations 7, 13 and 14 in Table S2). 2021 Computational and structural biotechnology journal Result HIV Q199H 106 111 Capsid 88 90 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Two PI-resistant mutations were identified at the interaction sites - G123E and H219Q. 2021 Computational and structural biotechnology journal Result HIV G123E;H219Q 70;80 75;85 PI 4 6 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. We compared the RMSF values of these residues between our three sets of apo simulations involving neutral H219, protonated H219 and mutated H219Q variants (Simulations 7-9 in Table S2). 2021 Computational and structural biotechnology journal Result HIV H219Q 140 145 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. While the average buried surface area between CA and CypA in the WT and mutant CA systems were comparable throughout the simulations, we observed transient detachment of CypA molecules in two of the CA subunits from the H219Q variant. 2021 Computational and structural biotechnology journal Result HIV H219Q 220 225 Capsid;Capsid;Capsid 46;79;199 48;81;201 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. While the interactions of G123E with the cleavage site residues occur within the same subunit of the MA-CA-SP1 polyprotein, inter-subunit interactions were observed for H219, whereby this residue contacted the cleavage site of an adjacent subunit. 2021 Computational and structural biotechnology journal Result HIV G123E 26 31 SP1;Matrix;Capsid 107;101;104 110;103;106 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. While we focused on the primary CypA binding site, since mutation and protonation of residue H219 does not affect the dynamics of the residues at the non-canonical interfaces, it is conceivable that CypA binding at these secondary sites may not be regulated by the H219Q mutation. 2021 Computational and structural biotechnology journal Result HIV H219Q 265 270 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. A report showed that mutation K22H was more frequent in patients failing to ART. 2021 Journal of ginseng research Result HIV K22H 30 34 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. All first K22N was detected in AIDS or low CD4+ T-cell count, whereas it was also reported in long-term nonprogressors (LTNPs). 2021 Journal of ginseng research Result HIV K22N 10 14 AIDS 31 35 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. In addition, R77Q was reported in Western LTNPs. 2021 Journal of ginseng research Result HIV R77Q 13 17 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. In our study of 470 Vpr proteins, there was no Q65R and F72L as shown in LTNPs. 2021 Journal of ginseng research Result HIV F72L;Q65R 56;47 60;51 Vpr 20 23 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Instead of the very rare K22H, we found an evolution from K22K to K22N in six HPs (3, 7, 8, 10, 11, and 19) (11.5%; 81/706 sequences) whose samples were not exposed to any antiretroviral drugs (except HP 19). 2021 Journal of ginseng research Result HIV K22H;K22K;K22N 25;58;66 29;62;70 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Interestingly, survival analysis revealed that Q135P was significantly associated with fast progression to AIDS, although K22N was not associated with it. 2021 Journal of ginseng research Result HIV K22N;Q135P 122;47 126;52 AIDS 107 111 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Of note, in HP 17, Q135P developed during GCT. 2021 Journal of ginseng research Result HIV Q135P 19 24 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Q135P in the vif gene is associated with rapid progression to AIDS. 2021 Journal of ginseng research Result HIV Q135P 0 5 Vif 13 16 AIDS 62 66 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Q135P was detected in nine patients including Plasma Donor O. 2021 Journal of ginseng research Result HIV Q135P 0 5 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. There was K22H in HP 9 (JQ066931-32), which is associated with low CD4+ T-cell counts and higher viral loads. 2021 Journal of ginseng research Result HIV K22H 10 14 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Thus, E25D and I61T showed a significantly high frequency in Cluster P, compared with that in the LCs and Cluster O (p < 0.0001). 2021 Journal of ginseng research Result HIV E25D;I61T 6;15 10;19 33466381 Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation. A comparison of RMS deviations for NBD-557 in WT complex, R425G mutant and gp120 complex with NBD is shown in Figure 6. 2021 Molecules (Basel, Switzerland) Result HIV R425G 58 63 gp120 75 80 33466381 Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation. Dynamics of the In-Silico Mutant Asn425Gly. 2021 Molecules (Basel, Switzerland) Result HIV N425G;N425L 33;33 42;42 33466381 Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation. In the Asn425Gly mutant, the one of amine hydrogen (H1--N) of NBD-557 forms a very strong hydrogen bond with backbone oxygen of Glycine and does not show the switching of position, as seen in WT complex (see Figure 5a,b). 2021 Molecules (Basel, Switzerland) Result HIV N425G 7 16 33466381 Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation. Since NBD-557 interacts strongly with Asn425, we performed in-silico mutation of Asn425 to Gly425 to monitor the effect of in-silico mutations. 2021 Molecules (Basel, Switzerland) Result HIV N425G 81 97 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Additional analyses carried out with rilpivirine resistance-associated mutations E138K/M184I or E138K/M184V showed that the combination of amino acid substitutions N348I and T369I had a dominant effect on the RNase H cleavage patterns observed with the PPT-containing 29RNA/28DNA template-primer complex (Figure 5). 2021 Viruses Result HIV E138K;E138K;M184I;M184V;N348I;T369I 81;96;87;102;164;174 86;101;92;107;169;179 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Although our studies suggest that connection subdomain mutations could affect PPT cleavage efficiency, we found no differences with the WT enzyme in assays carried out with an HIV-1ESP49 RT containing five amino acid substitutions in the connection subdomain (T355A/Q357M/K358R/A359G/S360A (5M)). 2021 Viruses Result HIV A359G;K358R;Q357M;S360A;T355A 278;272;266;284;260 283;277;271;289;265 RT 187 189 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Among them, E399D or G and T400A or S are known polymorphisms whose prevalence increases in patients treated with NNRTIs. 2021 Viruses Result HIV E399D;T400A 12;27 17;32 NNRTI 114 120 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. As previously shown for nevirapine, amino acid substitutions N348I/T369I reduced the efficiency of the WT enzyme in PPT cleavage assays carried out in the presence of doravirine (Figure 3), suggesting that those mutations could also contribute to doravirine resistance, despite being located away from the NNRTI binding site. 2021 Viruses Result HIV N348I;T369I 61;67 66;72 NNRTI 306 311 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. As shown in control experiments carried out with 29RNA/28DNA, 29RNA/29DNA and 29RNA/30DNA hybrids and the N348I/T369I RT (Figure 4B, right panel), the shortest RNA products rendering the correct cleavage at the PPT/U3 junction were obtained with the 29RNA/30DNA template-primer and corresponded to an RNase H cleavage window of 18 nucleotides. 2021 Viruses Result HIV N348I;T369I 106;112 111;117 RT 118 120 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Dominant Effects of N348I/T369I on the RNase H Cleavage Window at the PPT/U3 Junction. 2021 Viruses Result HIV N348I;T369I 20;26 25;31 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Histograms in Figure 4B show that the amino acid substitution E399D had negligible effects on the cleavage patterns obtained with template-primer 29RNA/28DNA. 2021 Viruses Result HIV E399D 62 67 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. However, the addition of E399G, T400A or T400S to N348I RT produced a slight increase in the amount of correctly processed PPT sequence, suggesting that those mutations could revert in part the RNase H cleavage window defect shown by N348I RT. 2021 Viruses Result HIV E399G;N348I;N348I;T400A;T400S 25;50;234;32;41 30;55;239;37;46 RT;RT 56;240 58;242 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. However, the N348I/T369I enzyme was unable to cleave efficiently the substrate at the correct G*A site when the distance to the 3' end of the DNA was reduced to 16 nucleotides, as in template-primer 29RNA/28RNA. 2021 Viruses Result HIV N348I;T369I 13;19 18;24 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Interestingly, N348I alone showed an intermediate phenotype with partial cleavage at the G*A when the 29RNA/28DNA hybrid was used (Figure 4B). 2021 Viruses Result HIV N348I 15 20 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Suppression of the NNRTI-mediated increase of PPT cleavage efficiency by N348I HIV-1BH10 RT and the double-mutant N348I/T369I has been associated with their reduced capacity to generate short RNA products. 2021 Viruses Result HIV N348I;N348I;T369I 73;114;120 78;119;125 NNRTI;RT 19;89 24;91 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. These results are consistent with the reduced RNase H activity shown by N348I and N348I/T369I HIV-1 RTs in assays carried out with different RNA/DNA hybrids, with or without PPTs, and suggest that the observed NNRTI effects could be attributed to a different positioning of the template-primer within the nucleic acid binding cleft. 2021 Viruses Result HIV N348I;N348I;T369I 72;82;88 77;87;93 NNRTI;RT 210;100 215;103 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. This engineered mutant, designated as G344E/D345P/ins346F, showed cleavage patterns identical to those obtained with WT HIV-2EHO RT (Figure 8) indicating that introduced changes had a relatively small effect on the location of the susceptible PPT sequence. 2021 Viruses Result HIV D345P;G344E 44;38 49;43 RT 129 131 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. We tested whether those amino acid substitutions could affect the RNase H PPT cleavage window in the presence of N348I in a similar manner as T369I. 2021 Viruses Result HIV N348I;T369I 113;142 118;147 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. While preferential cleavage at the G*A site of the PPT/U3 junction was observed with mutants E138K/M184I and E138K/M184V and the WT HIV-1BH10 RT, the presence of N348I/T369I in any of those sequence contexts altered the cleavage preferences and impaired correct processing of the PPT. 2021 Viruses Result HIV E138K;E138K;M184I;M184V;N348I;T369I 93;109;99;115;162;168 98;114;104;120;167;173 RT 142 144 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. Among NRTIs, except M184I (1), L74I (1), D67N (1), and T215I (1), the remaining mutations (75%, 12/16) only conferred potential resistance (score < 15) to NRTIs. 2021 BMC infectious diseases Result HIV D67N;L74I;M184I;T215I 41;31;20;55 45;35;25;60 NRTI;NRTI 6;155 11;160 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. K103N and Y181C were the most common TDRMs in NNRTI. 2021 BMC infectious diseases Result HIV Y181C;K103N 10;0 15;5 NNRTI 46 51 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. Only three youths carried TDRMs associated with PI resistance, and the I54M site caused broad resistance to PI drugs. 2021 BMC infectious diseases Result HIV I54M 71 75 PI;PI 48;108 50;110 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. The K103N group, Y181C group, and NRTI_TDRMs group had lower mean CD4 counts (337/mm395% CI: 246.42 ~ 427.57/mm3, 385/mm3 95% CI: 132.54 ~ 637.85/mm3, and 363.6/mm395% CI: 260.51 ~ 489.62/mm3, and 434/mm395% CI: 130.69 ~ 737.30/mm3, respectively) than the youths without TDRMs group (Table 3). 2021 BMC infectious diseases Result HIV K103N;Y181C 4;17 9;22 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. We divided subjects into the K103N group, Y181C group, NRTI group, PI group, and without TDRMs group. 2021 BMC infectious diseases Result HIV K103N;Y181C 29;42 34;47 NRTI;PI 55;67 59;69 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. Y181I/C and K103N were found in 7 and 9 infected individuals, respectively (Table 2). 2021 BMC infectious diseases Result HIV K103N;Y181C;Y181I 12;0;0 17;7;7 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Among the four mutants, the largest CSPs have been observed in the HSQC spectra of the MA T70R and L75G proteins. 2021 The Journal of biological chemistry Result HIV L75G;T70R 99;90 103;94 Matrix 87 89 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. As discussed above, to explain the role of MA trimerization in Env incorporation, it was suggested that the Q63R mutation in MA may stabilize the trimer structure such that MA lattices that form large hexamer holes are favored over those that feature small hexamer holes. 2021 The Journal of biological chemistry Result HIV Q63R 108 112 Env;Matrix;Matrix;Matrix 63;43;125;173 66;45;127;175 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. As indicated by the NMR data, substitution of Gln63 to Arg did not induce significant CSPs of residues in the trimeric interface. 2021 The Journal of biological chemistry Result HIV Q63R 46 58 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Crystal structure of the myr(-)MA Q63R protein. 2021 The Journal of biological chemistry Result HIV Q63R 34 38 Matrix 31 33 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. For T70R, the most significant CSPs are for residues localized in the vicinity of the mutation site (amino acid residues 69-76). 2021 The Journal of biological chemistry Result HIV T70R 4 8 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. For the A45E mutant, in addition to the CSPs observed for signals of residues 39-47, which are in the vicinity of the mutation site, resonances corresponding to Glu74 and Leu75 also exhibited significant CSPs. 2021 The Journal of biological chemistry Result HIV A45E 8 12 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Herein, we assessed whether the A45E, Q63R, T70R and L75G mutations in MA had any effect on the positioning of the myr group and/or the concentration-dependent myr-exposure. 2021 The Journal of biological chemistry Result HIV A45E;L75G;Q63R;T70R 32;53;38;44 36;57;42;48 Matrix 71 73 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. In this case, the effect of Q63R mutation could be direct on residues 74-76 or indirect through a local structural perturbation of residues 42-47, which are also close to residues 74-76. 2021 The Journal of biological chemistry Result HIV Q63R 28 32 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Interestingly, the sedimentation boundary for the L75G mutant is sharper than the WT and the other mutants and shifted to a smaller S value, suggesting that the monomer-trimer equilibrium is shifted toward the monomeric form. 2021 The Journal of biological chemistry Result HIV L75G 50 54 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Interestingly, the two crystal forms of myr(-)MA Q63R yielded structures that are essentially identical with slightly different parameters. 2021 The Journal of biological chemistry Result HIV Q63R 49 53 Matrix 46 48 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Interestingly, while the Ka values for the A45E, T70R, and Q63R mutant proteins are similar to the WT protein, the corresponding value for the L75G mutant is approximately twofold lower (Table 2), consistent with a lower trimer population. 2021 The Journal of biological chemistry Result HIV A45E;L75G;Q63R;T70R 43;143;59;49 47;147;63;53 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Next, we examined the Q63R mutant. 2021 The Journal of biological chemistry Result HIV Q63R 22 26 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. On the other hand, mutation of Leu75 to Gly induced substantial CSPs that extended beyond the mutation site, including residues in the trimer interface. 2021 The Journal of biological chemistry Result HIV L75G 31 43 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Point mutations in the HIV-1 MA protein (A45E, Q63R, T70R, and L75G) were made by site-directed mutagenesis of the MA gene embedded in a coexpression vector harboring yeast N-myristoyltransferase. 2021 The Journal of biological chemistry Result HIV A45E;L75G;Q63R;T70R 41;63;47;53 45;67;51;57 Matrix;Matrix 29;115 31;117 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Subsequent NMR studies revealed that point mutations in the N-terminal region of MA (e.g., V7R, L8A, or L8I) that impaired membrane targeting of Gag and inhibited virus assembly and release did not exhibit concentration-dependent myristate exposure. 2021 The Journal of biological chemistry Result HIV L8A;L8I;V7R 96;104;91 99;107;94 Gag;Matrix 145;81 148;83 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Taken together, the SV and SE data indicate that whereas none of the four mutations in MA significantly altered the monomer-trimer equilibrium in solution, the L75G mutation appears to shift the equilibrium toward the monomer form. 2021 The Journal of biological chemistry Result HIV L75G 160 164 Matrix 87 89 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The structure of the myr(-)MA Q63R trimer in both crystal forms is virtually identical to that of the WT myr(-)MA protein with slight orientation differences of monomers in the trimeric assembly. 2021 The Journal of biological chemistry Result HIV Q63R 30 34 Matrix;Matrix 27;111 29;113 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. This result demonstrates that substitution of Gln63 with Arg stabilizes the trimer structure of MA in the crystal lattice through H-bonding between the side chains of Arg63 and Ser67 located on two neighboring MA molecules. 2021 The Journal of biological chemistry Result HIV Q63R 46 60 Matrix;Matrix 96;210 98;212 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. This result suggests that substitution of Ala45 to Glu may have induced structural perturbations in the trimer interface. 2021 The Journal of biological chemistry Result HIV A45E 42 54 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. To be able to assess the structural changes in the MA trimer, we determined the high-resolution structure of myr(-)MA Q63R protein by X-ray crystallography. 2021 The Journal of biological chemistry Result HIV Q63R 118 122 Matrix;Matrix 51;115 53;117 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. We have shown that, similar to the WT MA protein, MA Q63R is in monomer-trimer equilibrium. 2021 The Journal of biological chemistry Result HIV Q63R 53 57 Matrix;Matrix 38;50 40;52 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. We obtained 1H-15N HSQC spectra for WT and A45E, Q63R, T70R, and L75G mutant MA proteins at three protein concentrations (50, 150, and 450 muM). 2021 The Journal of biological chemistry Result HIV A45E;L75G;Q63R;T70R 43;65;49;55 47;69;53;59 Matrix 77 79 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. A similar charge-dependent pattern of behaviour is seen when mutating R18, with R18K being more infectious than R18G (Fig 2C). 2021 PLoS pathogens Result HIV R18G;R18K 112;80 116;84 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. As expected, R18G was not able to assemble. 2021 PLoS pathogens Result HIV R18G 13 17 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. As K25A and K25N tubes had been observed under high salt assembly conditions, we varied CA and IP6 concentration and measured 350 nm absorbance (Fig 6E). 2021 PLoS pathogens Result HIV K25A;K25N 3;12 7;16 Capsid 88 90 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. As previously described, P38A showed a slightly faster tube assembly compared to WT. 2021 PLoS pathogens Result HIV P38A 25 29 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. At 10 mM IP6, the WT reaction was complete within 10 minutes, while the K25A reaction reached plateau after ~ 10 hours. 2021 PLoS pathogens Result HIV K25A 72 76 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. At a concentration of 100 muM dNTPs, where DNA synthesis in WT cores had increased > 2 logs, K25A showed very little activity. 2021 PLoS pathogens Result HIV K25A 93 97 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. At increased capsid (200muM) and increased IP6 (6 mM) concentrations we observed K25N assembly to tubes and cores (Fig 6E and 6F). 2021 PLoS pathogens Result HIV K25N 81 85 Capsid 13 19 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Choosing the highest dose of IP6, we repeated these experiments and compared WT CA to mutants K25A and K25R. 2021 PLoS pathogens Result HIV K25A;K25R 94;103 98;107 Capsid 80 82 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. For K25A, an increase in absorbance began to be observed after 15 hours. 2021 PLoS pathogens Result HIV K25A 4 8 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Given that K25A infectivity is ~1000-fold lower than WT, the proportion of correctly formed K25A mature cores could be as low as 0.1%. 2021 PLoS pathogens Result HIV K25A;K25A 11;92 15;96 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. However, the K25A and K25N mutants showed a profound loss of infectivity, with a reduction relative to wild-type of > 3 logs (Fig 2A and 2B). 2021 PLoS pathogens Result HIV K25A;K25N 13;22 17;26 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. However, we did not see the same phenomenon when using a K25A RFP virus. 2021 PLoS pathogens Result HIV K25A 57 61 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Importantly, while K25A is capable of carrying out reverse transcription and shows activity that is proportional to dNTP dose, it requires a > 10-fold higher concentration of dNTPs to achieve comparable levels of DNA synthesis as WT (WT gives > 103 copies at 100 muM dNTP whereas K25A requires 1000 muM for slightly fewer copies). 2021 PLoS pathogens Result HIV K25A;K25A 19;280 23;284 RT 51 72 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In contrast, addition of IP6 had no effect on K25A suggesting that a defect in either dNTP import and/or ability of IP6 to stabilise the capsid is limiting DNA synthesis in this mutant (Fig 2E). 2021 PLoS pathogens Result HIV K25A 46 50 Capsid 137 143 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In contrast, mutant K25A was far less efficient at carrying out reverse transcription. 2021 PLoS pathogens Result HIV K25A 20 24 RT 64 85 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In contrast, mutation of R18G leads to a loss of the ability to bind ligands (Fig 3A). 2021 PLoS pathogens Result HIV R18G 25 29 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In contrast, neither capsid cores nor tubes were observed for K25A and K25N. 2021 PLoS pathogens Result HIV K25A;K25N 62;71 66;75 Capsid 21 27 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In contrast, R18G did not form tubes but small spheres. 2021 PLoS pathogens Result HIV R18G 13 17 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In contrast, the failure of E29A to phenocopy K25A suggests that interaction between these residues is not important for viral fitness. 2021 PLoS pathogens Result HIV E29A;K25A 28;46 32;50 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In contrast, with K25A the CypA paint signal is extremely short-lived for most virions and the survival curve approaches baseline with a half-life of less than 1 minute. 2021 PLoS pathogens Result HIV K25A 18 22 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Increasing the IP6 concentration led to a dose dependent increase in both the kinetics and turbidity of both WT and K25A reactions. 2021 PLoS pathogens Result HIV K25A 116 120 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Interestingly, while mutants K25A, E28A and K30A all had a profound infectivity defect, E29A behaved similarly to wild-type (Fig 5C). 2021 PLoS pathogens Result HIV E28A;E29A;K25A;K30A 35;88;29;44 39;92;33;48 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. It showed a similar decrease in infection as P38A, a known CA instability mutant. 2021 PLoS pathogens Result HIV P38A 45 49 Capsid 59 61 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. K25A only showed a slight increase in absorbance compared to R18G and R18G/K25A which were not able to assemble at all. 2021 PLoS pathogens Result HIV K25A;R18G;R18G;K25A 75;61;70;0 79;65;74;4 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. K25A RFP virus gave poor RFP expression and there was no increase in GFP expression from the co-infecting WT GFP virus. 2021 PLoS pathogens Result HIV K25A 0 4 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. K25R was also able to form mature capsids, albeit with reduced yield and an increased proportion of larger cores. 2021 PLoS pathogens Result HIV K25R 0 4 Capsid 34 41 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Moreover, addition of either 0.1 or 1.0 mM IP6 failed to confer any stability on K25A. 2021 PLoS pathogens Result HIV K25A 81 85 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Moreover, the affinity of Atto488-labelled ATP binding to pre-assembled hexamers was not affected by K25A (Fig 3B). 2021 PLoS pathogens Result HIV K25A 101 105 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Moreover, their assembly kinetics were similar, albeit with an initial lag for K25A. 2021 PLoS pathogens Result HIV K25A 79 83 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Mutant K25R was substantially more infectious than K25A, with a ~ 1 log reduction in infection, highlighting the importance of maintaining a positive charge at this position. 2021 PLoS pathogens Result HIV K25A;K25R 51;7 55;11 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Mutant R18K/K25R was substantially less infectious than either single mutant alone, suggesting that mutation while preserving charge at one site does not prevent function at the other (Fig 2C). 2021 PLoS pathogens Result HIV K25R;R18K 12;7 16;11 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. R18G-RFP virus had a similar ability to saturate TRIM5 as K25R, but R18G-RFP infectivity was drastically lower compared to K25R (Fig 3D, RFP virus). 2021 PLoS pathogens Result HIV K25R;K25R;R18G;R18G 58;123;68;0 62;127;72;4 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Since these are very high IP6 concentrations we set up an assembly reaction with 500 muM WT and K25N with 10 muM IP6 incubated them for several hours, and analysed them via EM pictures (S6B Fig). 2021 PLoS pathogens Result HIV K25N 96 100 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Taken together, these results suggest that K25A mutants are severely impaired for IP6-driven assembly of capsid tubes, while capsid cones do not form or do so too rarely to be detected by in vitro methods. 2021 PLoS pathogens Result HIV K25A 43 47 Capsid;Capsid 105;125 111;131 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. The double mutant K25E/E29K showed poor infectivity, consistent with the importance and location of K25 to allow IP6 binding rather than E29K interaction (Fig 5C). 2021 PLoS pathogens Result HIV E29K;E29K;K25E 23;137;18 27;141;22 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. The hypostability mutant P38A, however, assembled cores with similar kinetics as WT. 2021 PLoS pathogens Result HIV P38A 25 29 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. The saturation ability of K25R RFP virus was ~ 1 log less efficient than WT virus and closely correlates with its 1 log less infectivity (Fig 2A). 2021 PLoS pathogens Result HIV K25R 26 30 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. The similar phenotypes of E28A and K30A are consistent with the notion that they participate in a direct interaction that is important for capsid assembly, particularly pentamer formation. 2021 PLoS pathogens Result HIV E28A;K30A 26;35 30;39 Capsid 139 145 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. These data indicate that the fraction of stable (or IP6-responsive) capsids for K25 mutants is reduced by at least 10-fold compared to wild-type, but whether there are stability differences between K25A and K25R cannot be determined with this method. 2021 PLoS pathogens Result HIV K25A;K25R 198;207 202;211 Capsid 68 75 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. These data suggest that the poor infectivity of K25A is likely to be caused, at least in part, by inefficient mature assembly. 2021 PLoS pathogens Result HIV K25A 48 52 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This indicates that not only is K25A poorly infectious but it also has too few stable capsids to efficiently saturate TRIM5. 2021 PLoS pathogens Result HIV K25A 32 36 Capsid 86 93 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This is consistent with previous data showing that R18G can form cores but is unable to reverse transcribe in cells. 2021 PLoS pathogens Result HIV R18G 51 55 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This is similar to previous data with R18G and provides further evidence that produced viruses are chimeric, as a mixture of fully wild type and fully mutant viruses would give rise to a linear relationship. 2021 PLoS pathogens Result HIV R18G 38 42 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This loss of infectivity is very similar to that displayed by the IP6- and nucleotide-binding mutant R18G. 2021 PLoS pathogens Result HIV R18G 101 105 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This may explain why we were unable to observe any K25A capsids; it would require the sampling of thousands of tomograms. 2021 PLoS pathogens Result HIV K25A 51 55 Capsid 56 63 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This result would be consistent with mutation of K25A reducing the efficiency of dNTP import. 2021 PLoS pathogens Result HIV K25A 49 53 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This suggests R18G viruses form higher order capsid assemblies that are largely non-infectious. 2021 PLoS pathogens Result HIV R18G 14 18 Capsid 45 51 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This suggests that K25R virus is less infectious because it has fewer stable capsids and not because it is less capable of mediating reverse transcription. 2021 PLoS pathogens Result HIV K25R 19 23 RT;Capsid 133;77 154;84 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This time the K25R RFP virus was able to dose-dependently saturate TRIM5 and an increase in the GFP signal was observed. 2021 PLoS pathogens Result HIV K25R 14 18 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This was also true for K25R: while K25R was slightly more stable than K25A in the presence of IP6, this effect is negligible when compared to WT (Fig 4C). 2021 PLoS pathogens Result HIV K25A;K25R;K25R 70;23;35 74;27;39 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This was not due to a failure in immature lattice processing because a similar number of immature cores were observed in WT and K25A virions and CA processing was identical (Figs 3C and S2C). 2021 PLoS pathogens Result HIV K25A 128 132 Capsid 145 147 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Thus, it is possible that K25A did not respond to IP6 addition because the mutant no longer binds or is stabilised by the ligand. 2021 PLoS pathogens Result HIV K25A 26 30 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Thus, we measured the K25A assembly reaction for 24h. 2021 PLoS pathogens Result HIV K25A 22 26 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. To determine the morphology of the assembled K25A CA, we analysed the sample by negative stain electron microscopy and observed tubes with dimensions of 44.7 +- 5.7 nm, consistent with that observed for WT and mutant CA under high salt conditions (Fig 6H). 2021 PLoS pathogens Result HIV K25A 45 49 Capsid;Capsid 50;217 52;219 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. To ensure that WT and K25A cores have incorporated similar levels of reverse transcriptase we measured enzymatic activity by RT ELISA (S2E Fig). 2021 PLoS pathogens Result HIV K25A 22 26 RT;RT 69;125 90;127 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. To test whether K25A undergoes reduced reverse transcription because of reduced stability or dNTP import we repeated our ERT experiments in the presence of IP6. 2021 PLoS pathogens Result HIV K25A 16 20 RT 39 60 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. To test whether the reduction in infectivity upon K25 mutation is similarly associated with a failure to undergo reverse transcription, we made a series of chimeric viruses by transfecting cells with different ratios of wild-type and K25A Gag plasmids. 2021 PLoS pathogens Result HIV K25A 234 238 RT;Gag 113;239 134;242 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Using this approach, we compared the behaviour of WT and K25A viruses in the presence and absence of IP6. 2021 PLoS pathogens Result HIV K25A 57 61 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. We co-infected cells with a consistent dose of WT virus that encodes a GFP reporter gene and a variety of mutant viruses that encode an RFP reporter gene (for instance, a single infection includes both WT-GFP and K25R-RFP). 2021 PLoS pathogens Result HIV K25R 213 217 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. We first incubated WT, K25A, K25R, K25N, P38A and R18G viruses under high salt conditions previously shown to induce the assembly of capsid tubes. 2021 PLoS pathogens Result HIV K25A;K25N;K25R;P38A;R18G 23;35;29;41;50 27;39;33;45;54 Capsid 133 139 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. We observed a complete loss of assembly for K25A and K25N and a decreased assembly for K25R (Fig 6D). 2021 PLoS pathogens Result HIV K25A;K25N;K25R 44;53;87 48;57;91 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. We observed a similar dose-dependent decrease in the infectivity of K25A chimeric viral particles (Fig 2D) as described for R18G. 2021 PLoS pathogens Result HIV K25A;R18G 68;124 72;128 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. We observed that K25A, K25R and K25N mutant viruses were capable of assembling capsid tubes like WT (Fig 6A-6C). 2021 PLoS pathogens Result HIV K25A;K25N;K25R 17;32;23 21;36;27 Capsid 79 85 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. We repeated this experiment with K25R. 2021 PLoS pathogens Result HIV K25R 33 37 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Whereas the majority of wild-type virions contained mature cores, no complete cores were observed for K25A (Figs 3C and S4 and S5). 2021 PLoS pathogens Result HIV K25A 102 106 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 1), either single mutants (D206L or D381L) or the combination of mutants (D206L/H547A or Y88F/D206L/H547A) would interfere with the hydrogen bonds between Tat and DAT, thereby affecting Tat-induced inhibition of DA transport. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;D206L;D381L;H547A 94;100;89;27;74;36;80 99;105;93;33;79;41;85 Tat;Tat 155;186 158;189 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 1c, two hydrogen bonds between Tat and DAT were eliminated by D206L/H547A, while. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A 62;68 67;73 Tat 31 34 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 1d shows that three hydrogen bonds were eliminated by Y88F/D206L/H547A. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F 59;65;54 64;70;58 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 3a, compared to WT hDAT (12.43 +- 2.50 pmol/min/105 cells), the Vmax values were decreased in D381L (4.54 +- 0.95 pmol/min/105 cells, t(8) = 2.95, p < 0.05) and not altered in D206L (13.09 +- 3.55 pmol/min/105 cells). 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 176;94 181;99 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 3b, compared to WT hDAT (26.62 +- 3.87 pmol/min/105 cells), the Vmax values were increased in D206L/H547A (40.82 +- 3.60 pmol/min/105 cells, t(6) = 3.12, p < 0.05) and decreased in Y88F/D206L/H547A (10.78 +- 0.98 pmol/min/105 cells, t(6) = 3.97, p < 0.01) respectively. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;H547A 186;192;181;94;100 191;197;185;99;105 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 3c, compared to WT hDAT (3.32 +- 0.58 pmol/105 cells), the maximal binding sites (Bmax) of [3H]WIN35,428 were not altered in D206L (2.87 +- 0.96 pmol/105 cells) and D381L (2.00 +- 0.63 pmol/105 cells) (ps > 0.05); however, the Kd values of D381L significantly increased (17.52 +- 6.57 nM, t(16) = 2.50, p < 0.05) in comparison to WT hDAT (5.98 +- 0.73 nM). 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L;D381L 125;165;240 130;170;245 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 3d, although the Bmax values of [3H]WIN35,428 were not altered in D206L/H547A and Y88F/D206L/H547A relative to WT hDAT, the Kd value was significantly decreased in Y88F/D206L/H547A (6.90 +- 1.26 nM, t(6) = 2.48, p < 0.05) in comparison to WT hDAT (12.53 +- 1.88 pmol/min/105 cells). 2021 Journal of neuroimmune pharmacology Result HIV D206L;D206L;H547A;H547A;Y88F;Y88F;D206L;H547A 87;169;93;175;82;164;66;72 92;174;98;180;86;168;71;77 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 5a, addition of rTat1 - 86 decreased DA uptake by 29 % in WT hDAT (t(6) = 4.39, p < 0.01) and by 32 % in D381L (t(6) = 2.47, p < 0.05), while Tat did not alter DA uptake in D206L relative to the respective controls. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 173;105 178;110 Tat 142 145 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 5c, t(6) = 4.16, p < 0.01), respectively, which was attenuated in D206L/H547A or Y88F/D206L/H547A. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;H547A 86;92;81;66;72 91;97;85;71;77 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 6a, D206L or D381L) and multiple mutants. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 4;13 9;18 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 6b, D206L/H547A and Y88F/D206L/H547A) in a concentration-dependent manner, indicating that these mutants do not alter zinc-mediated DA transport. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;H547A 25;31;20;4;10 30;36;24;9;15 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 6c), addition of Zn2+ resulted in an increase in the specific [3H]WIN35,428 binding in WT hDAT, D206L, and D381L in a concentration-dependent manner. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 96;107 101;112 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 7b, while Y88F/D206L/H547A did not alter the MPP+ efflux levels relative to WT hDAT, the MPP+ efflux levels in D206L/H547A were elevated at all indicated time (ps < 0.05, Bonferroni t-test) compared to WT hDAT, indicating D206L/H547A induces transporter conformational transitions. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;D206L;H547A;H547A 15;21;10;111;222;117;228 20;26;14;116;227;122;233 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 8c and d, a pilot study was designed to determine the time-dependent inhibitory effect of 2-BP on DA uptake, in which at zero time point, 2-BP had no inhibitory effect on Vmax or Km in WT hDAT and H547A relative to controls. 2021 Journal of neuroimmune pharmacology Result HIV H547A 197 202 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. A pilot study shows that MTSET concentration-dependently inhibited [3H]DA uptake in DAT E2C-I159C, while MTSET had no effect on [3H]DA uptake in DAT E2C-hDAT. 2021 Journal of neuroimmune pharmacology Result HIV E2C;E2C;I159C 88;149;92 91;152;97 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Additionally, 2-BP at zero or two-hour time point did not alter the Km values, whereas H547A mutant increased the Km values relative to WT hDAT (Table 5), which is consistent with our previous report. 2021 Journal of neuroimmune pharmacology Result HIV H547A 87 92 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. As shown in Table 1, compared to WT hDAT (1809 +- 493 nM), D381L decreased IC50 values for DA inhibiting [3H]DA uptake (338 +- 39 nM, t(5) = 2.80, p < 0.05), while D206L did not alter the IC50 value. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 164;59 169;64 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. As shown in Table 2, compared to WT hDAT, D206L/H547A preserved potency for DA, cocaine, or GBR12909 inhibiting [3H]DA uptake, while Y88F/D206L/H547A increased IC50 values for DA (1830 +- 587, t(9) = 2.53, p < 0.05) and decreased IC50 values for GBR12909 (180 +- 18, t(8) = 5.58, p < 0.001) compared to WT hDAT (467 +- 85 and 660 +- 84 nM, respectively). 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;H547A 138;144;133;42;48 143;149;137;47;53 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. As shown in Table 3, D206L and D381L did not alter the IC50 values for DA inhibiting [3H]WIN35,428 binding; however, D381L increased the IC50 values for cocaine (1480 +- 276, t(8) = 5.70, p < 0.001) and GBR12909 (2620 +- 404, t(8) = 3.50, p < 0.01) compared to WT hDAT (308 +- 55 and 770 +- 193, respectively). 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L;D381L 21;31;117 26;36;122 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Based on this theory, we hypothesized that the insertion of H547A into E2C I159C results in a significant increase in MTSET-induced inhibition of DA uptake. 2021 Journal of neuroimmune pharmacology Result HIV E2C;H547A;I159C 71;60;75 74;65;80 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Compared to controls, total DAT and surface DAT in D381L were decreased by 48 % (t(8) = 3.04, p < 0.05) and 41 % (t(8) = 3.44, p < 0.05), respectively, which correspond to the decreased Vmax in D381L shown in Table 1. 2021 Journal of neuroimmune pharmacology Result HIV D381L;D381L 51;194 56;199 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Compared to WT hDAT (0.45 +- 0.21 muM), Km value was increased in Y88F/D206L/H547A (1.92 +- 0.37 muM, t(6) = 3.45, p < 0.05) but not altered in D206L/H547A (0.69 +- 0.10 muM). 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;H547A 71;77;66;144;150 76;82;70;149;155 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. D206L, D206L/H547A, and Y88F/D206L/H547A Attenuate Tat-induced Inhibition of DA Transport. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;H547A;D206L 29;35;24;7;13;0 34;40;28;12;18;5 Tat 51 54 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Figure 6d shows that the specific [3H]WIN35,428 binding in WT hDAT was increased at 10 muM Zn2+ by 39 % (t(8) = 2.25, p < 0.05) and at 100 muM Zn2+ by 52 % (t(8) = 2.30, p < 0.05), respectively, which was attenuated in D206L/H547A or Y88F/D206L/H547A. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F;D206L;H547A 239;245;234;219;225 244;250;238;224;230 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. First, both E2C and E2C/H547A showed no effect of MTSET on DA uptake, suggesting that addition of H547A mutant does not alter DAT E2C control. 2021 Journal of neuroimmune pharmacology Result HIV E2C;E2C;H547A;H547A 12;130;24;98 15;133;29;103 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. H547A Mutant Renders the Transporter Into a More Outward-facing Conformation and Alters Basal Palmitoylation. 2021 Journal of neuroimmune pharmacology Result HIV H547A 0 5 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. However, at two-hour time point after addition of 2-BP, compared to the respective controls (in the absence of 2-BP) for WT hDAT (8.80 +- 0.92) and H547A (16.33 +- 0.99), addition of 15 muM 2-BP decreased the Vmax in WT hDAT (5.55 +- 0.92 remaining, t(6) = 2.50, p < 0.05) and H547A (5.56 +- 1.93 remaining, t(6) = 4.92, p < 0.01). 2021 Journal of neuroimmune pharmacology Result HIV H547A;H547A 148;277 153;282 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. In addition, both D206L and D381L did not alter the IC50 values for cocaine and GBR12909 relative to WT hDAT. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 18;28 23;33 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. In particular, the [3H]DA uptake by E2C-I159C was inhibited by the application of 1 mM MTSET by 55 % (t(2) = 11.13, p < 0.05) relative to no MTSET addition. 2021 Journal of neuroimmune pharmacology Result HIV E2C;I159C 36;40 39;45 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Interestingly, although the increased Vmax was observed in D206L/H547A, this mutant did not alter total and surface DAT relative to WT hDAT. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A 59;65 64;70 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Moreover, compared to E2C-I159C (46.0 +- 6.0), [3H]DA uptake was further inhibited by 34 % in E2C-I159C/H547A (30.4 +- 3.5, t(8) = 8.93, p < 0.001), which was reversed in the negative control E2C-I159A/H547A (59.7 +- 5.7, t(8) = 2.92, p < 0.05), suggesting that mutation of His547 may change the transporter conformational state toward an outward open conformation. 2021 Journal of neuroimmune pharmacology Result HIV E2C;H547A;H547A;I159A;I159C;I159C 22;104;202;196;26;98 25;109;207;201;31;103 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Neither D206L nor D381L altered the MPP+ efflux across the indicated times compared to the respective WT hDAT. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 8;18 13;23 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Neither total nor surface DAT was altered in D206L relative to WT hDAT, which corresponds to the unaltered Vmax values as shown in. 2021 Journal of neuroimmune pharmacology Result HIV D206L 45 50 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Next, we tested the effect of H547A mutant on the E2C-I159C reactivity. 2021 Journal of neuroimmune pharmacology Result HIV E2C;H547A;I159C 50;30;54 53;35;59 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Our data show that the Vmax was not altered in D206L but increased in H547A. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A 47;70 52;75 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Our previous study demonstrates that the H547A-induced increase in Vmax is mediated by alterations in basal PKC activity. 2021 Journal of neuroimmune pharmacology Result HIV H547A 41 46 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Previous studies show that [3H]DA uptake in cells expressing E2C I159C was inhibited in the presence of MTSET, whereas no inhibition of DA uptake was observed in E2C, suggesting a stabilization of the transporter in a conformation open to the extracellular environment. 2021 Journal of neuroimmune pharmacology Result HIV E2C;E2C;I159C 61;162;65 64;165;70 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Second, compared to E2C control, [3H]DA uptake was inhibited in E2C-I159C (t(8) = 6.34, p < 0.001). 2021 Journal of neuroimmune pharmacology Result HIV E2C;E2C;I159C 20;64;68 23;67;73 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Single mutations on Y88F or H547A may result in the significant disruption of the binding between Tat and DAT (; Yuan et al. 2021 Journal of neuroimmune pharmacology Result HIV H547A;Y88F 28;20 33;24 Tat 98 101 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Tat Mutant K19A Attenuates Tat-induced Inhibition of DA Transport. 2021 Journal of neuroimmune pharmacology Result HIV K19A 11 15 Tat;Tat 0;27 3;30 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The DAT expression in Y88F/D206L/H547A was significantly decreased by 58 % in total (t(4) = 2.76, p < 0.05) and 73 % in surface (t(4) = 4.38, p < 0.05) fractions, respectively, compared to WT hDAT, which corresponds to the significant decrease in Vmax (Table 2. 2021 Journal of neuroimmune pharmacology Result HIV D206L;H547A;Y88F 27;33;22 32;38;26 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The I159C mutant was inserted into DAT background (E2C) in which the two external endogenous cysteines were mutated to alanines (C90A-C306A), resulting in DAT E2C I159C. 2021 Journal of neuroimmune pharmacology Result HIV C306A;C90A;E2C;E2C;I159C;I159C 134;129;51;159;4;163 139;133;54;162;9;168 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The insertion of H547A into E2C or E2C-I159C (E2C/H547A, E2C-I159C/H547A or E2C-I159A/H547A) displayed a differential reaction to 1 mM MTSET. 2021 Journal of neuroimmune pharmacology Result HIV E2C;E2C;H547A;H547A;H547A;H547A;I159A;I159C;I159C 28;35;17;50;67;86;80;39;61 31;38;22;55;72;91;85;44;66 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The reaction of the cysteine to MTSET could inactivate the transporter, which allow us to use [3H]DA uptake as a functional readout for a mutation of hDAT at I159 (isoleucine to cysteine, I159C) reactivity. 2021 Journal of neuroimmune pharmacology Result HIV I159C 188 193 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The WT rTat1 - 86-induced decrease in [3H]DA uptake and [3H]WIN35,428 binding was attenuated by K19A, indicating mutated Tat K19 residue disrupts the DAT-Tat interaction. 2021 Journal of neuroimmune pharmacology Result HIV K19A 96 100 Tat;Tat 121;154 124;157 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Therefore, D206L is unlikely to directly interfere with the binding of dopamine with DAT, making this residue an ideal target for interfering with Tat-DAT binding without disrupting transporter function. 2021 Journal of neuroimmune pharmacology Result HIV D206L 11 16 Tat 147 150 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Therefore, the mutation of these residues (D206L or D381L) is expected to impair the hydrogen bond between DAT and Tat. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 43;52 49;57 Tat 115 118 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. These results indicate that neither D206L nor D381L mutant alters the zinc-mediated [3H]WIN35,428 binding relative to WT hDAT. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 36;46 41;51 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Third, DA uptake was inhibited by 65 % in E2C-I159C/H547A (30.4 +- 3.52, t(8) = 5.24, p < 0.001) and 31 % in E2C-I159A/H547A (59.7 +- 5.7, t(8) = 2.17, p < 0.05) relative to E2C (86.5 +- 6.0). 2021 Journal of neuroimmune pharmacology Result HIV E2C;H547A;H547A;I159A;I159C 174;52;119;113;46 177;57;124;118;51 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. This study further tested the DAT Y88-Tat K19 interaction by mutated K19 residue (K19A). 2021 Journal of neuroimmune pharmacology Result HIV K19A 82 86 Tat 38 41 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. To determine whether the H547A-induced increase in DA uptake is a result of alteration of basal palmitoylation levels, we determined the kinetic parameters (Vmax and Km) of DA uptake in WT hDAT and H547A in the presence or absence of 2-bromopalmitate (2-BP), a palmitoylation inhibitor. 2021 Journal of neuroimmune pharmacology Result HIV H547A;H547A 25;198 30;203 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. To determine whether the mutations of Asp206 and Asp381 on hDAT influence basal DAT function, kinetic analysis of [3H]DA uptake was performed on WT hDAT, D206L and D381L. 2021 Journal of neuroimmune pharmacology Result HIV D206L;D381L 154;164 159;169 Asp;Asp 38;49 41;52 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. To explore potential conformational changes in H547A, we utilized an assay to test the accessibility to the reactivity of cysteine inserted into position 159 (Cys159) in transmembrane 3 of hDAT. 2021 Journal of neuroimmune pharmacology Result HIV H547A 47 52 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. We have previously reported that Tyr88 on hDAT interacts with Tat residue K19 and that mutated Tyr88 (Y88F) attenuates Tat-induced inhibition of DA transport (, 2016a). 2021 Journal of neuroimmune pharmacology Result HIV Y88F 102 106 Tat;Tat 62;119 65;122 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Within the vehicle groups, the Vmax was increased in H547A compared to WT hDAT (t(5) = 5.51, p < 0.01). 2021 Journal of neuroimmune pharmacology Result HIV H547A 53 58 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. Individuals infected with the subtype CRF01_AE were the most likely to develop a PI-associated mutation, followed by those infected with CRF07_BC; the mutation sites primarily comprised M46V (0.35%) and Q58E (0.43%) mutations. 2021 BMC infectious diseases Result HIV M46V;Q58E 186;203 190;207 PI 81 83 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. Individuals infected with the subtypes CRF01_AE and CRF08_BC were the most likely to develop NNTRI-associated mutations; the most common mutations were V179E (7.21%), V179D (3.21%), and V106I (1.91%). 2021 BMC infectious diseases Result HIV V106I;V179D;V179E 186;167;152 191;172;157 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. Patients infected with the CRF01_AE subtype were the most likely to develop NRTI-associated mutations; the most common mutations were M41L (0.17%) and D67G (0.17%). 2021 BMC infectious diseases Result HIV D67G;M41L 151;134 155;138 NRTI 76 80 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. The genotype CRF55_01B was the most likely to harbour V179E mutations. 2021 BMC infectious diseases Result HIV V179E 54 59 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. Despite no mention of use of any INIs by the clinical reports, three patient sequences had the Y143R mutation in major viral quasispecies and one in minor viral quasispecies, which confers resistance to raltegravir (RAL). 2021 BMC infectious diseases Result HIV Y143R 95 100 IN 33 37 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. Most of the DRMs in the minor viral quasispecies were observed in V82A mutation (n = 13) in protease and K65R (n = 5), K103N (n = 7) and M184V (n = 5) in reverse transcriptase. 2021 BMC infectious diseases Result HIV K103N;K65R;M184V;V82A 119;105;137;66 124;109;142;70 RT;PR 154;92 175;100 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Predominant NNRTIs mutations were K103N, Y181C, G190A, H221Y, and K101E; NRTIs were M184V, Y115F, K65R, K70R, D67N and PIs were I54V, F53L and V82A (Table 2). 2020 The Pan African medical journal Result HIV D67N;F53L;G190A;H221Y;I54V;K101E;K103N;K65R;K70R;M184V;V82A;Y115F;Y181C 110;134;48;55;128;66;34;98;104;84;143;91;41 114;138;53;60;132;71;39;102;108;89;147;96;46 NNRTI;NRTI;PI 12;73;119 18;78;122 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Although these variants still existed at follow-up, the frequencies of the mutations M184VI, K103N and P225H decreased over time, and most of them remained at frequencies of more than 20%. 2021 Pathogens (Basel, Switzerland) Result HIV K103N;M184I;M184V;P225H 93;85;85;103 98;91;91;108 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. At baseline, mutations with a frequency of 20% and above were NRTI-related, such as M184VI (2.0%, 1/49), and NNRTI-related like K103N (14.3%, 7/49), E138AG (4.1%, 2/49), V179D (2.0%, 1/49) and P225H (2.0%, 1/49). 2021 Pathogens (Basel, Switzerland) Result HIV E138A;E138G;K103N;M184I;M184V;P225H;V179D 149;149;128;84;84;193;170 155;155;133;90;90;198;175 NNRTI;NRTI 109;62 114;66 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. At the 20% detection threshold, NGS detected all the mutations identified by SS except a V106M mutation in one patient, as there were mixtures in the first (G to R) and third nucleotides (A to R) in the codon at Sanger sequencing. 2021 Pathogens (Basel, Switzerland) Result HIV V106M 89 94 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Drug resistance mutations (DRMs) were detected at 12 positions in the partial pol region by Sanger sequencing (Figure 1), including one in the protease (PR) region, an accessory protease inhibitor (PI)-related resistance mutation (Q58E), and eleven in the reverse transcriptase (RT) region, including one nucleotide reverse transcriptase inhibitor (NRTI)-related (M184V), and ten others were NNRTI-related. 2021 Pathogens (Basel, Switzerland) Result HIV M184V;Q58E 364;231 369;235 RT;RT;PR;PR;NNRTI;NRTI;Pol;PI;PR;RT 256;316;143;178;392;349;78;198;153;279 277;337;151;186;397;353;81;200;155;281 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. However, some minority DRMs at frequencies of 1%-5% disappeared, including N83D with PI-related, K70E, T215A, and K219E with NRTI-related and K101E, Y181C, H221Y and K238T with NNRTI-related, while others emerged, such as NNRTI-related V106A in patient GX088 at a frequency of 8.7%, and L23I, I47V and I84V with PI-related, D67N and F77L with NRTI-related and L100V and F227L with NNRTI-related, which appeared at frequencies of 1%-5% (Figure 3). 2021 Pathogens (Basel, Switzerland) Result HIV D67N;F227L;F77L;H221Y;I47V;I84V;K101E;K219E;K238T;K70E;L100V;L23I;N83D;T215A;V106A;Y181C 324;370;333;156;293;302;142;114;166;97;360;287;75;103;236;149 328;375;337;161;297;306;147;119;171;101;365;291;79;108;241;154 NNRTI;NNRTI;NNRTI;NRTI;NRTI;PI;PI 177;222;381;125;343;85;312 182;227;386;129;347;87;314 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. However, the frequency of K103N in one patient (GX064) had dropped from 43.7% to 15.3%, and the mutation K103N in another patient (CQ046) with a frequency of 36.9% disappeared (Supplementary Materials). 2021 Pathogens (Basel, Switzerland) Result HIV K103N;K103N 26;105 31;110 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. In addition, NGS detected three more mutations in three patients: Y188C, E138A and K103N, at frequencies of 22.96%, 27.38% and 43.68%, respectively. 2021 Pathogens (Basel, Switzerland) Result HIV E138A;K103N;Y188C 73;83;66 78;88;71 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. It is interesting that this low-frequency K65R mutation is significantly unevenly distributed among subtypes; 5.7% (2/35) in CRF01_AE, when compared with 95.1% (58/61) in CRF07_BC and 93.1% (54/58) in CRF08_BC (p < 0.001). 2021 Pathogens (Basel, Switzerland) Result HIV K65R 42 46 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. K65R was the most common low-frequency DRM with frequencies between 1% and 9%, concentrated at frequencies from 2% to 5%. 2021 Pathogens (Basel, Switzerland) Result HIV K65R 0 4 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. M46LI was the common low-frequency PI-related mutation, with frequencies ranging from 1% to 13%. 2021 Pathogens (Basel, Switzerland) Result HIV M46I;M46L 0;0 5;5 PI 35 37 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Moreover, K65R was still the most common low-frequency mutation at the follow-up. 2021 Pathogens (Basel, Switzerland) Result HIV K65R 10 14 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Other low-frequency NRTI-related mutations were K70QE, F77L, T215AI and K219QE. 2021 Pathogens (Basel, Switzerland) Result HIV F77L;K219E;K219Q;K70E;K70Q;T215A;T215I 55;72;72;48;48;61;61 59;78;78;53;53;67;67 NRTI 20 24 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Other PI-related mutations such as L10F, I47V, I50V, F53L, I54VT and N83D have the mutation frequency of about 2%. 2021 Pathogens (Basel, Switzerland) Result HIV F53L;I47V;I50V;I54T;I54V;L10F;N83D 53;41;47;59;59;35;69 57;45;51;64;64;39;73 PI 6 8 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. The most common drug resistance mutation was K103N (13.2%), followed by V179D (6.3%) and E138AGK (3.5%). 2021 Pathogens (Basel, Switzerland) Result HIV E138A;E138G;E138K;K103N;V179D 89;89;89;45;72 96;96;96;50;77 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Within a year, some minority DRMs at frequencies 1%-10% remained unchanged, including: PI-related D30N, M46LI, I54VT and N88D, NRTI-related K65R and NNRTI-related Y188CHL. 2021 Pathogens (Basel, Switzerland) Result HIV D30N;I54T;I54V;K65R;M46I;M46L;N88D;Y188C;Y188H;Y188L 98;111;111;140;104;104;121;163;163;163 102;116;116;144;109;109;125;170;170;170 NNRTI;NRTI;PI 149;127;87 154;131;89 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. A total of 12 samples contained 13 NNRTIs-resistance mutations:V106I in 4 samples, V179E, V179D mutations each in 3 samples, E138A mutations in 2 samples and V106M in 1 sample. 2021 Drug design, development and therapy Result HIV E138A;V106I;V106M;V179D;V179E 125;63;158;90;83 130;68;163;95;88 NNRTI 35 41 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. In one participant, two NRTIs-resistance mutations (M184V, K70E) were observed. 2021 Drug design, development and therapy Result HIV K70E;M184V 59;52 63;57 NRTI 24 29 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. One accessory INSTIs-resistance mutation (E157Q) was observed in another sample, which can contribute to resistance if present along with other major resistance mutations resistance to RAL and EVG. 2021 Drug design, development and therapy Result HIV E157Q 42 47 INSTI 14 20 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Only one major INSTIs-resistance mutation (E138K) was detected in one sample. 2021 Drug design, development and therapy Result HIV E138K 43 48 INSTI 15 21 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. The M184V mutation can contribute to resistance if present along with other major resistance mutations high level resistance to lamivudine (3TC) and emtricitabine, and low-level resistance to didanosine and abacavir. 2021 Drug design, development and therapy Result HIV M184V 4 9 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. The most frequently observed polymorphic variants were T124A, T125A and S283G, followed by L101I, T112V, I135L, and K136Q. 2021 Drug design, development and therapy Result HIV I135L;K136Q;L101I;S283G;T112V;T124A;T125A 105;116;91;72;98;55;62 110;121;96;77;103;60;67 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Two patients harbored PIs-resistance mutations: Q58E mutation in one patient, 3 major mutations (M46I, I54V, V82A) and 2 accessory mutations (L10F, Q58E) in another individual (Table 2). 2021 Drug design, development and therapy Result HIV I54V;L10F;M46I;Q58E;Q58E;V82A 103;142;97;48;148;109 107;146;101;52;152;113 PI 22 25 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. All carried M184V mutation in their historic plasma (point 1 in Table 1), but no K65R/N/E mutations. 2021 The Journal of antimicrobial chemotherapy Result HIV K65E;K65N;K65R;M184V 81;81;81;12 89;89;89;17 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. At PBMC sampling 9 out of 12 subjects were taking regimens including lamivudine or emtricitabine, and 2 out of 9 carried M184V in pDNA. 2021 The Journal of antimicrobial chemotherapy Result HIV M184V 121 126 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. However, youths with M184V tended to have more time with undetectable VL since M184V appearance in the last positive historical genotype in plasma to PBMCs sampling [5.1 (IQR: 3.3-7.7) versus 3.6 (IQR: 2.1-6.2), P = 0.9] and tended to have greater time under lamivudine or emtricitabine exposure before historical genotype in plasma [6.1 (IQR: 4-6.2) versus 2.4 (IQR: 1.8-5.8), P = 0.6] but lower time under lamivudine or emtricitabine from the first M184V detection in plasma to PBMCs sampling [1.4 (IQR: 0.9-3.3) versus 4.4 (IQR: 2.2-7.6), P = 0.3]. 2021 The Journal of antimicrobial chemotherapy Result HIV M184V;M184V;M184V 21;79;451 26;84;456 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Nine (75%) subjects did not present M184V/I in pDNA after at least 1 year of viral suppression. 2021 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 36;36 43;43 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. No statistically significant differences were found between patients with or without M184V in pDNA (Table 1). 2021 The Journal of antimicrobial chemotherapy Result HIV M184V 85 90 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. None of the 12 patients presented K65R/N/E in their pDNA. 2021 The Journal of antimicrobial chemotherapy Result HIV K65E;K65N;K65R 34;34;34 42;42;42 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. PBMCs were collected between 2010 and 2018, after a median of 8 years (IQR: 4.6-10.9) from first M184V detection in plasma genotype and after a median of 4 years (IQR: 2.1-6.5) of virological suppression. 2021 The Journal of antimicrobial chemotherapy Result HIV M184V 97 102 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. The median time between the start of the lamivudine/emtricitabine regimen and the first detection of historical M184V mutation in plasma was 3.8 years (IQR: 1.8-6.1). 2021 The Journal of antimicrobial chemotherapy Result HIV M184V 112 117 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Youths with and without M184V at pDNA showed similar time (median years) under ART to PBMCs collection [14.3 (IQR: 13.4-15.8) versus 13.7 (IQR: 10.8-14.7), P = 0.7]. 2021 The Journal of antimicrobial chemotherapy Result HIV M184V 24 29 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. Interestingly, two samples, one collected in 2013 and the other in 2016, presented concurrently the mutations E138A, G140S, and Q148H, which confer high-level resistance to all INSTIs, including BIC (Table 2). 2021 International journal of environmental research and public health Result HIV E138A;G140S;Q148H 110;117;128 115;122;133 INSTI 177 183 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. Meanwhile, the T97TA (38%) integrase mutation, when combined with any other major mutation, has been reported to have a synergistic effect, which can reduce susceptibility to these drugs. 2021 International journal of environmental research and public health Result HIV T97A;T97T 15;15 20;20 IN 27 36 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. Meanwhile, the Y143R mutation, found in 6.0% of the sequences, is related to high-level resistance to RAL. 2021 International journal of environmental research and public health Result HIV Y143R 15 20 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. Nevertheless, when combined with Q148QKH, they can provide high-level resistance to RAL or EVG and reduce DTG or BIC efficacy. 2021 International journal of environmental research and public health Result HIV Q148H;Q148K;Q148Q 33;33;33 40;40;40 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. Previous studies have demonstrated that HIV-1 patient samples harboring these mutations (E138EA, G140S, and Q148HKR) show high-level resistance to INSTIs, and these combinations were identified in 1.52% of our sequences. 2021 International journal of environmental research and public health Result HIV E138A;E138E;G140S;Q148H;Q148K;Q148R 89;89;97;108;108;108 95;95;102;115;115;115 INSTI 147 153 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. The D232DN, detected in 46% of the samples with mutations, is an accessory mutation reported in patients receiving EVG and RAL. 2021 International journal of environmental research and public health Result HIV D232D;D232N 4;4 10;10 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. The E138EA and G140S mutations by themselves do not reduce or improve INSTIs susceptibility. 2021 International journal of environmental research and public health Result HIV E138A;E138E;G140S 4;4;15 10;10;20 INSTI 70 76 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. The most frequent integrase mutations in our analyzed patient samples were the Q148HKR (31%), G140S (28%), and, although at lower frequencies, we were able to identify the N155H, S147G, Y143R, and E138EA (Figure 2A). 2021 International journal of environmental research and public health Result HIV E138A;E138E;G140S;N155H;Q148H;Q148K;Q148R;S147G;Y143R 197;197;94;172;79;79;79;179;186 203;203;99;177;86;86;86;184;191 IN 18 27 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. The N155H mutation, associated with high-level resistance to RAL and EVG, was identified in 19% of the samples. 2021 International journal of environmental research and public health Result HIV N155H 4 9 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. The S147G was observed in 10.0% of patients, which moderately reduces susceptibility to this drug. 2021 International journal of environmental research and public health Result HIV S147G 4 9 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. This sequence did not harbor any major or accessory drug resistance mutations to INSTIs; however, it presented a polymorphic accessory mutation (L74I) common among 20% of the studied patients but with no significant effect by itself. 2021 International journal of environmental research and public health Result HIV L74I 145 149 INSTI 81 87 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. We also identified the resistance-accessory mutations D232DN, T97TA, E157Q, and G163GART (Figure 2B). 2021 International journal of environmental research and public health Result HIV D232D;D232N;E157Q;G163A;G163G;G163R;G163T;T97A;T97T 54;54;69;80;80;80;80;62;62 60;60;74;88;88;88;88;67;67 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. A change of charge in the protein interaction site (AA 12-39) and the S163C mutation in the ExxxLL binding motif of Nef increased, whereas the loss of valine at position 148 (V148X) decreased, the HIV-1 infectivity of Bal26-pseudotyped HIV-1 produced in the presence of SERINC5 (Figure 5B and Supplementary Table S2). 2021 Viruses Result HIV S163C;V148X 70;175 75;180 Nef 116 119 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. For instance, a change in the number of positively charged amino acids was often observed in combination with an increased length of the AA 12-39 region (30.1%), in combination with the S163C mutation in ExxxLL (22.8%) or combined with both an increased length and the S163C mutation (9.8%). 2021 Viruses Result HIV S163C;S163C 186;269 191;274 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. In addition, multiple amino acid variations in Nef (subtype B HIV-1) were identified to play a role in SERINC3 and SERINC5 antagonism (Figure 1) including 8R, 9S, 11P, 12G, 14A/P/S, 15A, 21K/R, 28E, 43I, N51T, 54D, 63E, 81F, H116N, 120F, V148L/X, 157N, 158K, 161N, M168I/X, 182E and 188S, of which some specifically affected SERINC3 (8R, 9S, 11P, 12G, 14A, 15A, 21K, 28E, 43I, 182E and 188S) or SERINC5 (14S, 21R, 54D, 63E, 81F, 120F, 157N and 158K). 2021 Viruses Result HIV H116N;M168I;M168X;N51T;V148L;V148X 225;265;265;204;238;238 230;272;272;208;245;245 Nef 47 50 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. Individuals with an HIV-1 variant containing arginine at position 8 (8R) in Nef progressed after AIDS (log rank, p = 0.017; relative hazard (RH), 1.66; 95% CI, 1.09-2.55; p = 0.018), asparagine at position 157 (157N) in Nef died earlier from AIDS-related disease (log rank, p = 0.041; RH, 2.52; 95% CI, 1.00-6.31; p = 0.048) and the R178G Nef mutation showed faster progression to AIDS (log rank, p = 0.026; RH, 1.78; 95% CI, 1.06-2.97; p = 0.037) and AIDS-related death (log rank, p = 0.040; RH, 1.84; 95% CI, 1.00-3.37; p = 0.048) (Figure 6 and Supplementary Table S3). 2021 Viruses Result HIV R178G 333 338 Nef;Nef;Nef 76;220;339 79;223;342 AIDS;AIDS;AIDS 97;381;452 101;385;456 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. Nef variants containing 21R and H116N also increased infectivity, whereas the variant R178G decreased infectivity, albeit not significantly (Figure 5B and Supplementary Table S2). 2021 Viruses Result HIV H116N;R178G 32;86 37;91 Nef 0 3 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. Previous reports indicated that some naturally occurring mutations in Nef could affect both SERINC3 and SERINC5 (N51T, H116N, V148L/X, 161N and M168I/X), while others only affected SERINC3 (8R, 9S, 11P, 12G, 14A, 15A, 21K, 28E, 43I, 182E and 188S) or SERINC5 (14S, 21R, 54D, 63E, 81F, 120F, 157N and 158K). 2021 Viruses Result HIV H116N;M168I;M168X;N51T;V148L;V148X 119;144;144;113;126;126 124;151;151;117;133;133 Nef 70 73 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. Recent reports demonstrated that three specific sites in Nef, the amino acids 12 to 39, the ExxxLL motif (S163C) and the AP-2 binding site (R178G), were identified to be involved in Nef function (Figure 1). 2021 Viruses Result HIV R178G;S163C 140;106 145;111 Nef;Nef 57;182 60;185 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The change of charge in the protein interaction site (AA 12-39) and the presence of amino acids 12G, N51T, H116N and 188S in Nef were associated with a significant increased infectivity of Bal26-pseudotyped HIV-1 produced in the presence of SERINC3, while increased length of the protein interaction site (AA12-39), 9S, 43I and S163C also increased and 11P, 14A, V148X, 161N and R178G decreased infectivity, albeit not significantly (Figure 5A and Supplementary Table S2). 2021 Viruses Result HIV H116N;N51T;R178G;S163C;V148X 107;101;379;328;363 112;105;384;333;368 Nef 125 128 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The previously described polymorphisms (8R, 9S, 11P, 12G, 14A/P, 15A, 21K/R, 28E, 43I, N51T, 54D, 63E, 81F, H116N, 120F, V148L/X, 157N, 158K, 161N, M168I/X, 182E and 188S) were observed at different frequencies and are shown in Table 1. 2021 Viruses Result HIV H116N;M168I;M168X;N51T;V148L;V148X 108;148;148;87;121;121 113;155;155;91;128;128 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The S163C mutation in the ExxxLL motif was observed in 39.8% (49/123) of the patients, while the R178G mutation, located in the AP-2 binding site, was observed in 17.9% (22/123) of the patients. 2021 Viruses Result HIV R178G;S163C 97;4 102;9 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. We observed that individuals with HIV-1 containing the 8R, 157N or R178G polymorphism in Nef showed an accelerated disease progression. 2021 Viruses Result HIV R178G 67 72 Nef 89 92 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. Furthermore, HIV-1 JR-CSFWT replicates at a higher efficiency when compared to the replication kinetics of HIV-1 JR-CSFK65R_M184V (Figure 3D,E). 2021 Viruses Result HIV M184V 124 129 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. HIV-1 JR-CSFK65R_M184V replicated more than 3-logs lower than HIV-1 JR-CSFWT. 2021 Viruses Result HIV M184V 17 22 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. Interestingly, one primary HIV-1 isolate had a lower replication capacity than HIV-1 JR-CSFK65R_M184V. 2021 Viruses Result HIV M184V 96 101 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. It has been previously shown that the K65R mutation reduces replication capacity up to 55% compared to the wildtype virus, but when paired with the M184V mutation replication capacity was reduced up to 70% compared to the wildtype in in vitro experiments. 2021 Viruses Result HIV K65R;M184V 38;148 42;153 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. M184V and K65R are drug resistance mutations located in the reverse transcriptase of the viral pol gene. 2021 Viruses Result HIV K65R;M184V 10;0 14;5 RT;Pol 60;95 81;98 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. NGS analysis confirmed the absence of both mutations in pJR-CSFWT, while pJR-CSFK65R_M184V contained both mutations. 2021 Viruses Result HIV K65R;M184V 80;85 84;90 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. On every fourth infection plate, the two control viruses, HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V, were added as intra-assay controls. 2021 Viruses Result HIV M184V 94 99 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. The mixture ratio at day 2 was approximately 50/50, but over the course of the experiment, HIV-1 JR-CSFWT replicated at a higher efficiency and outcompeted HIV-1 JR-CSFK65R_M184V (Figure S1B). 2021 Viruses Result HIV M184V 173 178 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. The parallel infection replication curves depict a clear difference with HIV-1 JR-CSFWT replicating more efficient than HIV-1 JR-CSFK65R_M184V (Figure S1A). 2021 Viruses Result HIV M184V 137 142 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. The replication capacities of the primary HIV-1 isolates exhibited a large distribution from 103-106, with the two control viruses representing the high (HIV-1 JR-CSFWT) and low (HIV-1 JR-CSFK65R_M184V) replication capacities (Figure 3F). 2021 Viruses Result HIV M184V 196 201 33806576 A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells. To achieve control viruses that represent both high and low replication competence, the HIV-1 full-length wildtype plasmid pJR-CSFWT was used to produce the high replication competent virus, as well as, utilized to generate the less replication competent virus, pJR-CSFK65R_M184V. 2021 Viruses Result HIV M184V 274 279 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. Amongst the individuals previously exposed to RAL ART (seven out of eleven), DRMs selected whilst failing their current DTG based regimens were E138K, G140A, Q148R; and N155H Figure 3. 2021 Viruses Result HIV E138K;G140A;N155H;Q148R 144;151;169;158 149;156;174;163 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. The four individuals failing DTG cART but with no documented prior exposure to RAL, their selected DRMs were E138K, G140A, Q148K, A128T; G118R, E138K; N155ND and T66A, G118R, E138EAKT Figure 3. 2021 Viruses Result HIV A128T;E138A;E138E;E138K;E138K;E138K;E138T;G118R;G118R;G140A;N155D;N155N;Q148K;T66A 130;175;175;175;109;144;175;137;168;116;151;151;123;162 135;183;183;183;114;149;183;142;173;121;157;157;128;166 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. 4c) confirming that the A1V mutation conferred resistance to the compound. 2021 Retrovirology Result HIV A1V 24 27 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. 5b) suggesting that the I201V mutant gained infectivity in the presence of the compound. 2021 Retrovirology Result HIV I201V 24 29 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. CA: I201V mutation conferred partial resistance and compound dependent phenotype on the virus. 2021 Retrovirology Result HIV I201V 4 9 Capsid 0 2 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. In addition, the A1V mutant viruses displayed similar replication kinetics in the presence as well as the absence of the compound. 2021 Retrovirology Result HIV A1V 17 20 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Replacing threonine with a glycine (SP1: T10G) in both IndieC1 and ZM247 markedly increased the CA-SP1 accumulation by nearly 2-fold in the presence of the BVM analog CV-8611 whereas mutating the residue 9 (SP1: S9N) had no effect as compared to the WT virus. 2021 Retrovirology Result HIV S9N;T10G 212;41 215;45 SP1;SP1;SP1;Capsid 36;99;207;96 39;102;210;98 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Similar assays were performed using IndieC1 and ZM247 WT viruses and their mutants (SP1:S9N, SP1:T10G and SP1:S9N/T10G). 2021 Retrovirology Result HIV T10G;S9N 114;110 118;113 SP1;SP1;SP1 84;93;106 87;96;109 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Similarly, the ZM247 SP1: T10G mutant also displayed a greater decrease in the infectivity (55%) than the SP1: S9N mutant as compared to the WT in the presence of the CV-8611. 2021 Retrovirology Result HIV S9N;T10G 111;26 114;30 SP1;SP1 21;106 24;109 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. SP1: A1V mutant was resistant to the BVM analog. 2021 Retrovirology Result HIV A1V 5 8 SP1 0 3 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Swapping glycine with a threonine at the residue 10 in K3016 SP1: G10T reduced the accumulation of the CA-SP1 intermediate by 2.5 fold in the presence of the BVM analog CV-8611 whereas replacing asparagine with a serine at SP1 residue 9 in K3016 SP1: N9S had negligible effect as compared to the WT. 2021 Retrovirology Result HIV G10T;N9S 66;251 70;254 SP1;SP1;SP1;SP1;Capsid 61;106;223;246;103 64;109;226;249;105 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The double mutant K3016 SP1: N9S/G10T displayed similar sensitivity as the single mutant SP1:G10T. 2021 Retrovirology Result HIV G10T;N9S 33;29 37;32 SP1;SP1 24;89 27;92 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The double mutant SP1: S9N/T10G also displayed a similar increase in the CA-SP1 accumulation as the single mutant SP1:T10G in the presence of CV-8611. 2021 Retrovirology Result HIV S9N;T10G 23;27 26;31 SP1;SP1;SP1;Capsid 18;76;114;73 21;79;117;75 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The infectivity of the I201V mutant was significantly reduced by 70% in comparison to the WT in the absence of the analog. 2021 Retrovirology Result HIV I201V 23 28 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The relative infectivity of the double mutant ZM247 SP1: S9N/T10G further decreased in the presence of the BVM analog CV-8611. 2021 Retrovirology Result HIV S9N;T10G 57;61 60;65 SP1 52 55 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The relative infectivity of the mutant IndieC1 carrying SP1: T10G and SP1: S9N/T10G mutation was drastically decreased by fivefold in comparison to the WT virus in the presence of the analog CV-8611. 2021 Retrovirology Result HIV S9N;T10G;T10G 75;61;79 78;65;83 SP1;SP1 56;70 59;73 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. These results confirmed that the CA: I201V mutation conferred partial resistance and compound dependent phenotype on the virus. 2021 Retrovirology Result HIV I201V 37 42 Capsid 33 35 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. To analyze the effect of the CA: I201V mutation, HEK-293T cells were transfected with the K3016 WT and the mutant virus in the absence or the presence of two concentrations of BVM analog CV-8613 (100 nM and 500 nM). 2021 Retrovirology Result HIV I201V 33 38 Capsid 29 31 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Unlike the WT, the mutant A1V did not display an accumulation of the CA-SP1 intermediate in the presence of the BVM analog. 2021 Retrovirology Result HIV A1V 26 29 SP1;Capsid 72;69 75;71 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. We introduced the SP1:A1V mutation into the K3016 WT backbone to generate the mutant clone and characterized its resistance profile by analyzing the effect of this mutation on CA-SP1 processing, infectivity, and virus replication. 2021 Retrovirology Result HIV A1V 22 25 SP1;SP1;Capsid 18;179;176 21;182;178 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. We observed a 3.5-fold increase in the infectivity of the single mutant K3016 SP1: G10T and the double mutant K3016 SP1: N9S/G10T as compared to the WT virus produced in presence of CV-8611 whereas the relative infectivity of the single mutant K3016 SP1: N9S increased by 1.5 fold only in the presence of the analog. 2021 Retrovirology Result HIV G10T;G10T;N9S;N9S 83;125;121;255 87;129;124;258 SP1;SP1;SP1 78;116;250 81;119;253 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. We sequenced the entire Gag and protease encoding region of the virus at the peak replication day and identified two mutations acquired by the virus- SP1: A1V and CA: I201V. 2021 Retrovirology Result HIV A1V;I201V 155;167 158;172 PR;SP1;Gag;Capsid 32;150;24;163 40;153;27;165 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. We swapped the residues at SP1 position 9 and 10 between the HIV-1 subtype C strains by site-directed mutagenesis and constructed two single mutants K3016 SP1: N9S and K3016 SP1: G10T and a double mutant K3016 SP1: N9S/G10T. 2021 Retrovirology Result HIV G10T;G10T;N9S;N9S 179;219;160;215 183;223;163;218 SP1;SP1;SP1;SP1 27;155;174;210 30;158;177;213 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. 3a, c), therefore allowing model building of the C-terminal portion of SP1, from T8I to M14. 2021 Communications biology Result HIV T8I 81 84 SP1 71 74 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. 3c, green arrow), but not in GagDeltaMA T8I map. 2021 Communications biology Result HIV T8I 40 43 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. Altogether, these results indicate that cleavage at both proteolytic sites flanking SP1 are impaired by the T8I mutation, which supports the formation of a stable and extended SP1 helix. 2021 Communications biology Result HIV T8I 108 111 SP1;SP1 84;176 87;179 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. As such, the helix stabilization imparted by the T8I mutation may explain the observed delays in SP1 NC cleavage. 2021 Communications biology Result HIV T8I 49 52 SP1;NC 97;101 100;103 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. If the T8I mutation stabilizes the extended six-helix bundle, this may affect PR processing of these cleavage sites. 2021 Communications biology Result HIV T8I 7 10 PR 78 80 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. The refined atomic model shows that the T8I mutation in SP1 stabilizes the Gag hexamer by enhancing the hydrophobicity in one face of the amphipathic CA-SP1 helix. 2021 Communications biology Result HIV T8I 40 43 SP1;SP1;Gag;Capsid 56;153;75;150 59;156;78;152 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. The T8I mutation reduces SP1 dynamics and impairs proteolytic cleavage. 2021 Communications biology Result HIV T8I 4 7 SP1 25 28 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. The T8I mutation was shown to quench the dynamics of SP1 by MAS NMR, and potentially stabilize a continuous helical conformation. 2021 Communications biology Result HIV T8I 4 7 SP1;Matrix 53;60 56;62 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. To resolve the structure of the full CA-SP1 six helix bundle, we utilized HIV-1 Gag proteins containing the T8I mutation at SP1 for stabilizing bundle assembly. 2021 Communications biology Result HIV T8I 108 111 SP1;SP1;Gag;Capsid 40;124;80;37 43;127;83;39 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. We thus tested the effect of the T8I mutation on PR-mediated cleavage of Gag assemblies using in vitro cleavage assays. 2021 Communications biology Result HIV T8I 33 36 Gag;PR 73;49 76;51 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. A total of 11.8% (34/287) of the sequences contained five different IN accessory mutations, namely Q95K, T97A, G149A, E157Q and D232N. 2021 BMC infectious diseases Result HIV D232N;E157Q;G149A;Q95K;T97A 128;118;111;99;105 133;123;116;103;109 IN 68 70 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Eleven NOPs (I72V, L74MVI, L101I, T112V, T124A, T124A, G134N, I135V, K136K/Q, V201I and T206S) are part of the CCD, and the remaining five (T218I, L234I, A265V, R269K and S283G) belong to the CTD. 2021 BMC infectious diseases Result HIV A265V;G134N;I135V;I72V;K136K;K136Q;L101I;L234I;L74I;L74M;L74V;R269K;S283G;T112V;T124A;T124A;T206S;T218I;V201I 154;55;62;13;69;69;27;147;19;19;19;161;171;34;41;48;88;140;78 159;60;67;17;76;76;32;152;25;25;25;166;176;39;46;53;93;145;83 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. In addition, the remaining other six substitutions; M50I, L74I, L74M, Q95K, G118S and P145S showed no changes in the number or type of interactions, implying no strong effect on the protein structure and function (Table 1). 2021 BMC infectious diseases Result HIV G118S;L74I;L74M;M50I;P145S;Q95K 76;58;64;52;86;70 81;62;68;56;91;74 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Moreover, T66A, Q148H, N155H, D232N and R263K mutations all indicated a loss of interactions with neighbouring residues after the introduction of substitutions, while only the N155H mutation gained an additional interaction with the 3' terminal viral DNA Adenine21 (Table 1). 2021 BMC infectious diseases Result HIV D232N;N155H;N155H;Q148H;R263K;T66A 30;23;176;16;40;10 35;28;181;21;45;14 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Mutations G149A and D232N occurred together in one sequence (0.3%). 2021 BMC infectious diseases Result HIV D232N;G149A 20;10 25;15 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Notably, one sequence dating back from 2010 had two major mutations; Q148H and R263K in combination with two other minor mutations G149A and D232N. 2021 BMC infectious diseases Result HIV D232N;G149A;Q148H;R263K 141;131;69;79 146;136;74;84 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Only substitution Q95K resulted in a slightly stabilizing effect of 0.146Kcal/Mol. 2021 BMC infectious diseases Result HIV Q95K 18 22 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Protein drug interaction analysis of energy minimized complexes revealed interesting findings as accessory mutation E157Q made only one MG ion interaction and D232N none, while substitutions T66A, T97A, Q148H, R263K and N155H all had ionic interactions with two MG ions as well as with DDE motif active site residues and the 3' terminal viral DNA nucleotides (Table 2) and. 2021 BMC infectious diseases Result HIV D232N;E157Q;N155H;Q148H;R263K;T66A;T97A 159;116;220;203;210;191;197 164;121;225;208;215;195;201 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. The consensus sequences generated using the database-derived HIV-1 CRF02_AG sequences (n = 287) and cohort sequences (n = 20), identified 20 naturally occurring polymorphisms (NOPS): E11D,K14R, V31I, M50I, I72V, L74MVI, L101I, T112V, T124A, G134N, I135V, K136K/Q, V201I, T206S, T218I, L234I, A265V, R269K, S283G. 2021 BMC infectious diseases Result HIV A265V;E11D;G134N;I135V;I72V;K136K;K136Q;K14R;L101I;L234I;L74I;L74M;L74V;M50I;R269K;S283G;T112V;T124A;T206S;T218I;V201I;V31I 292;183;241;248;206;255;255;188;220;285;212;212;212;200;299;306;227;234;271;278;264;194 297;189;246;253;210;262;262;192;225;290;218;218;218;204;304;311;232;239;276;283;269;198 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. the M50I, T66A, L74I, L74M, T97A, G118S, S119R, P145S, Q148H, G149A, N155H, E157Q, D232N and R263K substitutions resulted in destabilizing effects of - 0.582, - 0.703 -1.069, - 0.93, - 1.051, - 0.492, - 0.091, - 0.485, - 0.133, - 0.421, - 0.975, - 1.111, - 0.512 and - 0.455 Kcal/Mol each, respectively. 2021 BMC infectious diseases Result HIV D232N;E157Q;G118S;G149A;L74I;L74M;M50I;N155H;P145S;Q148H;R263K;S119R;T66A;T97A 83;76;34;62;16;22;4;69;48;55;93;41;10;28 88;81;39;67;20;26;8;74;53;60;98;46;14;32 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. The T97A showed four polar contacts for T97 compared to the three of A97 (Table 1). 2021 BMC infectious diseases Result HIV T97A 4 8 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Three of these (E11D, K14R and V31I) belong to the NTD, whereas M50I belongs to the loop region connecting the NTD and CTD. 2021 BMC infectious diseases Result HIV E11D;K14R;M50I;V31I 16;22;64;31 20;26;68;35 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Two mutations, Q148H and R263K, occurred together in one sequence (0.3%), whereas T66A and N155H were present individually in one sequence each. 2021 BMC infectious diseases Result HIV N155H;Q148H;R263K;T66A 91;15;25;82 96;20;30;86 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. We identified 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) having major INSTI RAMs: T66A, Q148H, R263K and N155H. 2021 BMC infectious diseases Result HIV N155H;Q148H;R263K;T66A 127;110;117;104 132;115;122;108 INSTI 92 97 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. All had baseline M184V/I, and 1 had additional NRTI RAMs. 2021 AIDS research and therapy Result HIV M184I;M184V 17;17 24;24 NRTI 47 51 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. All of these patients had a baseline M184V/I and 21/32 (66%) had >= 1 additional NRTI mutation. 2021 AIDS research and therapy Result HIV M184I;M184V 37;37 44;44 NRTI 81 85 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. All patients had virus with the M184V/I however 23 (59%) had additional NRTI resistance associated mutations (RAMs). 2021 AIDS research and therapy Result HIV M184I;M184V 32;32 39;39 NRTI 72 76 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Both functional monotherapy patients had a baseline HIV-1 RNA >= 50 copies/mL, one was switched from ABC/3TC/DRV/r to DTG/RPV (Table 2, Patient 5) and historical genotypic testing revealed an M184V/I and E138E/K which predicted that DTG was the only fully active agent in the study DCR. 2021 AIDS research and therapy Result HIV E138E;E138K;M184I;M184V 204;204;192;192 211;211;199;199 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. The other patient was switched from TDF/FTC/EVG/c to DTG/ABC/3TC (Table 2, Patient 6) and historical genotypic testing revealed an M184V/I, M41L, T215Y and L74/I which predicted that DTG was the only fully active agent in the study DCR. 2021 AIDS research and therapy Result HIV M184I;M184V;M41L;T215Y 131;131;140;146 138;138;144;151 33952315 Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa. In CRF02_AG sequences, A83V, a previously inferred escape variant in known CTL epitopes in the p17 region of gag was the only non-consensus amino acid variant associated with a lower VRC (Table 4). 2021 Retrovirology Result HIV A83V 23 27 Gag 109 112 33952315 Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa. In subtype A sequences, the only non-consensus polymorphism associated with decreased VRC was P497L, while non-consensus amino acid variants K69Q, S125N, L147I, A158V and R380K, were associated with significantly higher VRC (Table 5). 2021 Retrovirology Result HIV A158V;K69Q;L147I;P497L;R380K;S125N 161;141;154;94;171;147 166;145;159;99;176;152 33952315 Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa. This result was consistent with previous reports linking A83V to reduced viral fitness in subtypes B and CRF01_AE. 2021 Retrovirology Result HIV A83V 57 61 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. For NRTIs, these were M184VI (55.6%), T215SNY (22.2%), and K65R (18.5%). 2021 Infectious diseases Result HIV K65R;M184I;M184V;T215N;T215S;T215Y 59;22;22;38;38;38 63;28;28;45;45;45 NRTI 4 9 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. FTC and 3TC were also predicted with high-level DR (55.6%), which however is associated with a higher fitness cost due to the point mutation M184V. 2021 Infectious diseases Result HIV M184V 141 146 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Nonetheless, in patient 279A K70R co-occurred with K219E, the TAM variant D67G, and T69D, suggesting undisclosed use of AZT (http://hivdb.stanford.edu). 2021 Infectious diseases Result HIV D67G;K219E;K70R;T69D 74;51;29;84 78;56;33;88 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Same for patients 310A, 1181A, and 309A who carried K65R and Y115F strains while on AZT. 2021 Infectious diseases Result HIV K65R;Y115F 52;61 56;66 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. The most frequent resistant genotypes to NNRTIs were K103N (37.04%), Y181CY (22.2%), and A98AG (18.5%). 2021 Infectious diseases Result HIV A98A;A98G;K103N;Y181C;Y181Y 89;89;53;69;69 94;94;58;75;75 NNRTI 41 47 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Three of them, including 1 previously on PMTCT (279A, 310A, 1181A) were taking regimens containing TDF, which also selects for TAMs (ie, K70R). 2021 Infectious diseases Result HIV K70R 137 141 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. PANDAA identified the presence of K103N in three samples. 2020 AAS open research Result HIV K103N 34 39 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. PANDAA was completed on patient-derived amplicons of 103 ARV naive individuals for the K103N, V106M and M184V DRMs using PANDAA. 2020 AAS open research Result HIV K103N;M184V;V106M 87;104;94 92;109;99 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. The three samples with K103N were the same samples that Sanger sequencing detected. 2020 AAS open research Result HIV K103N 23 28 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. As seen in Figure 6, when GS-6207 is removed from its complex with the M66I CA mutant, after ~5 ns thetorsion of the I66 side chain spontaneously switches to the conformation in the apo mutant (shown in red) and maintains that rotamer state during the remaining ~15 ns of the MD trajectory. 2021 Viruses Result HIV M66I 71 75 Capsid 76 78 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. As shown in Figure 9B, the binding site in the M66I CA mutant exists in two conformational states, A () and B (), with their apo state occupancies , since . 2021 Viruses Result HIV M66I 47 51 Capsid 52 54 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. As shown in Figure 9B, the global free energy minimum () in the apo M66I CA coincides with the rotamer observed in the M66I-ZW-1261 and M66I-PF74 complexes (see Figure 7 and Figure 8). 2021 Viruses Result HIV M66I;M66I;M66I 68;119;136 72;123;140 Capsid 73 75 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Based on these observed conformational properties of the binding site, we explore the physical reason for the loss of the binding affinity of GS-6207 due to the M66I mutation. 2021 Viruses Result HIV M66I 161 165 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Below, we report the results of the further analysis of the MD free energy simulations to gain insight into the mechanism of the M66I resistance mutation. 2021 Viruses Result HIV M66I 129 133 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Here, since GS-6207 binding to state A of the M66I mutant results in a steric clash (Figure 4),is highly unfavorable compared with . 2021 Viruses Result HIV M66I 46 50 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Importantly, this conformational free energy differencecorrelates well with the relative binding free energycaused by the M66I CA mutation for GS-6207 binding (Table 2). 2021 Viruses Result HIV M66I 122 126 Capsid 127 129 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. In contrast, the rotamer populated in the M66I-GS-6207 complex (, Figure 6) has a higher conformational free energy ofthan the global free energy minimum ofin the apo M66I CA structure (Figure 9B). 2021 Viruses Result HIV M66I;M66I 42;167 46;171 Capsid 172 174 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. In the next section, we show more quantitatively that this contrasting behavior of the presence and absence of a ligand-induced protein side chain reorganization in the mutant and wild-type CA is key to understanding the M66I resistance to GS-6207. 2021 Viruses Result HIV M66I 221 225 Capsid 190 192 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. In this section, we show that the loss of binding affinity for the GS-6207 due to the M66I CA mutation can be largely explained by the fact that the GS-6207 forces the M66I CA mutant to undergo a conformational switch to a higher free energy state, while such a conformational change is absent in the case of GS-6207 binding to the wild-type CA or when the mutant CA binds with PF74 and its derivative ZW-1261. 2021 Viruses Result HIV M66I;M66I 86;168 90;172 Capsid;Capsid;Capsid;Capsid 91;173;342;364 93;175;344;366 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Table 1 shows the experimental EC50 results for PF74, ZW-1261, and GS-6207 against the wild-type and the M66I mutant HIV-1 viruses. 2021 Viruses Result HIV M66I 105 109 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The Binding of GS-6207 to the M66I CA Mutant Forces the I66 Side Chain to Adopt a Higher Free Energy Rotamer State to Avoid Steric Clashes. 2021 Viruses Result HIV M66I 30 34 Capsid 35 37 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The results show that the all-atom free energy model with an explicit solvent successfully accounts for the effect of the M66I mutation on the change in the binding of the three antivirals to the CA dimer. 2021 Viruses Result HIV M66I 122 126 Capsid 196 198 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The structure of the M66I-GS-6207 complex corresponds to a representative structure in the final state following the FEP simulation that mutates the MET66 in the WT-GS-6207 complex to ILE using the FEP+ module of Schrodinger Inc.; see details in the Method and Materials Section. 2021 Viruses Result HIV M66I 21 25 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. Therefore, it is the protein side chain reorganization free energythat contributes the most to the relative binding free energy caused by the M66I CA mutation, . 2021 Viruses Result HIV M66I 142 146 Capsid 147 149 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. To quantitatively estimate the free energy change associated with the GS-6207-induced conformational reorganization, we calculated the free energy profiles using well-tempered metadynamics simulations along theof the side chain of residue 66 in the apo forms of the wild-type CA and the M66I mutant (Figure 9). 2021 Viruses Result HIV M66I 287 291 Capsid 276 278 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. To show that this new conformer in the M66I-GS-6207 complex was indeed of s higher free energy, we performed the following sets of MD simulations: (1) starting from the structure of the M66I-GS-6207 complex but with the ligand removed from the binding pocket; (2) starting from the structure of the M66I-GS-6207 complex; (3) starting from the structures of the M66I-ZW-1261 and M66I-PF74 complexes with the ligands removed from the binding pocket; and (4) starting from the structures of the M66I-ZW-1261 and M66I-PF74 complexes. 2021 Viruses Result HIV M66I;M66I;M66I;M66I;M66I;M66I;M66I 39;186;299;361;378;492;509 43;190;303;365;382;496;513 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. To test whether the all-atom MD free energy model can capture this trend, we examined the changes in the binding free energy caused by the M66I mutation during the binding of the three antivirals to the CA dimer by using FEP (free energy perturbation) to calculate the relative binding free energyfor each of the antivirals. 2021 Viruses Result HIV M66I 139 143 Capsid 203 205 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. To understand why the M66I mutation causes such a significant loss of binding affinity to GS-6207 and why the loss of affinity is bigger than it is for ZW-1261 and PF74, we first examine the apo structure of the M66I mutant (Figure 3), which is obtained by manually removing the ligand from the M66I-GS-6207 complex and running an MD simulation on the apo protein in a solution for 20 ns. 2021 Viruses Result HIV M66I;M66I;M66I 22;212;295 26;216;299 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. We then compared the MD structures of the M66I CA mutant in complex with GS-6207, ZW-1261, and PF74 (Figure 5). 2021 Viruses Result HIV M66I 42 46 Capsid 47 49 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. When comparing this value with the relative binding free energy caused by the M66I CA mutation(Table 2) and noting that the GS-6207 binding to the wild-type CA is not accompanied by a shift in the protein conformational states (Figure 9A), it is easy to show that the intrinsic binding free energy when the M66I mutant is restrained to the B state, , is close to the total absolute binding free energy for the wild-type CA, . 2021 Viruses Result HIV M66I;M66I 78;307 82;311 Capsid;Capsid;Capsid 83;157;420 85;159;422 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. While Figure 9B shows that the binding of GS-6207 to the M66I mutant induces a side chain conformational change to a higher free energy rotamer, this is not the case for the wild-type CA. 2021 Viruses Result HIV M66I 57 61 Capsid 184 186 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. While the I66 side chain in the M66I-ZW-1261 or PF74 complexes essentially maintained the same rotamer state as that of the one in the apo protein in Figure 3, in the M66I-GS-6207 complex the I66 side chain moved to a new, higher-energy rotamer, with the gamma2 carbon and delta carbon switching positions. 2021 Viruses Result HIV M66I;M66I 32;167 36;171 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. While the M66I mutation reduces the potency of GS-6207 by up to ~84,000-fold, the activities of ZW-1261 and PF74 are only reduced by 68-fold and 83-fold, respectively. 2021 Viruses Result HIV M66I 10 14 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. A similar phenomenon may also explain the relatively low treated/naive prevalence ratios for E138K and M230I. 2021 Viruses Result HIV E138K;M230I 93;103 98;108 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. A62V had a naive prevalence below 0.2% in each of the other subtypes and increased in prevalence from 4.1 to 6.9% since 2009. 2021 Viruses Result HIV A62V 0 4 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. A62V, another tenofovir-associated mutation, was not considered a candidate SDRM because it had a prevalence of 6.5% in subtype A sequences owing to a founder effect among subtype A6 sequences, one of the dominant variants in countries of the former Soviet Union. 2021 Viruses Result HIV A62V 0 4 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Although we excluded sequences meeting previously defined criteria for APOBEC-mediated G-to-A hypermutation, we cannot exclude the possibility that some of the G190E mutations were APOBEC-mediated. 2021 Viruses Result HIV G190E 160 165 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Despite being associated with high-level resistance to each of the NNRTIs G190E is uncommon in NNRTI-experienced persons. 2021 Viruses Result HIV G190E 74 79 NNRTI;NNRTI 67;95 73;100 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. E138R and M230I are not present in Table 4 because they occurred in fewer than 0.1% of NNRTI-experienced persons. 2021 Viruses Result HIV M230I;E138R 10;0 15;5 NNRTI 87 92 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Each of these seven, with the exception of V179M were on three or more expert mutation lists. 2021 Viruses Result HIV V179M 43 48 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Few data are available linking L89T to reduced susceptibility to specific PIs. 2021 Viruses Result HIV L89T 31 35 PI 74 77 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Figure 1 shows the locations of the NRTI-SDRMs and the six candidate mutations (K65N, T69deletion and K70G/N/Q/T) within the three-dimensional structure of the polymerase coding region of p66 HIV-1 RT. 2021 Viruses Result HIV K65N;K70G;K70N;K70Q;K70T 80;102;102;102;102 84;112;112;112;112 Pol;NRTI;RT 160;36;198 170;40;200 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Figure 2 shows the locations of the NNRTI-SDRMs and the six candidate mutations (E138K/Q, V179L, H221Y, and F227C/L) within the three-dimensional structure of the polymerase coding region of p66 and the finger domain of p51 HIV-1 RT. 2021 Viruses Result HIV E138K;E138Q;F227C;F227L;H221Y;V179L 81;81;108;108;97;90 88;88;115;115;102;95 Pol;NNRTI;RT 163;36;230 173;41;232 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Figure 3 shows the locations of the PI-SDRMs and the three candidate mutations (L10F, T74P, and L89V) within the three-dimensional structure of HIV-1 protease. 2021 Viruses Result HIV L10F;L89V;T74P 80;96;86 84;100;90 PR;PI 150;36 158;38 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Five SDRMs increased in prevalence among NRTI-experienced persons including K65R, K70E, Y115F, and M184V/I. 2021 Viruses Result HIV K65R;K70E;M184I;M184V;Y115F 76;82;99;99;88 80;86;106;106;93 NRTI 41 45 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Four SDRMs increased in prevalence in RTI-naive persons including K103N, V106M, and G190A/E while L100I decreased in prevalence among RTI-naive persons. 2021 Viruses Result HIV G190A;G190E;K103N;L100I;V106M 84;84;66;98;73 91;91;71;103;78 RT;RT 38;134 41;137 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. L10F has been shown to be an accessory DRM associated with reduced in vitro lopinavir and darunavir susceptibility. 2021 Viruses Result HIV L10F 0 4 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. M230I also had a low treated/naive ratio of 4. 2021 Viruses Result HIV M230I 0 5 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. N88S decreased in prevalence among PI-naive persons while no other mutations changed in prevalence among PI-naive persons. 2021 Viruses Result HIV N88S 0 4 PI;PI 35;105 37;107 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. One of these DRMs (L89T) increased in prevalence among PI-experienced persons while 14 decreased in prevalence among PI-experienced persons. 2021 Viruses Result HIV L89T 19 23 PI;PI 55;117 57;119 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Seven of these DRMs increased in prevalence among NNRTI-experienced persons since 2009 including E138K/Q, V179L/M, H221Y, and F227C/L. 2021 Viruses Result HIV E138K;E138Q;F227C;F227L;H221Y;V179L;V179M 97;97;126;126;115;106;106 104;104;133;133;120;113;113 NNRTI 50 55 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Seven SDRMS increased in prevalence among NNRTI-experienced persons including K101E, Y181V, Y188C, G190S, P225H, and M230L while four decreased in prevalence including L100I, V106A, K101P, and V181I. 2021 Viruses Result HIV G190S;K101E;K101P;L100I;M230L;P225H;V106A;V181I;Y181V;Y188C 99;78;182;168;117;106;175;193;85;92 104;83;187;173;122;111;180;198;90;97 NNRTI 42 47 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Six of the candidate NNRTI-SDRMs that increased in prevalence are associated with reduced susceptibility to rilpivirine (E138K/Q, V179L, and H221Y) or doravirine (F227C/L) and are present on three or more of the 2020 expert mutation lists. 2021 Viruses Result HIV E138K;E138Q;F227C;F227L;H221Y;V179L 121;121;163;163;141;130 128;128;170;170;146;135 NNRTI 21 26 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. T74P and L89V were considered to be accessory mutations based on analyses of phenotypic and clinical data derived from the POWER studies that led the FDA approval of darunavir. 2021 Viruses Result HIV L89V;T74P 9;0 13;4 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The DRMs with the highest prevalence since 2009 included L10F (6.7%), K20T (4.1%), and K43T (3.0%). 2021 Viruses Result HIV K20T;K43T;L10F 70;87;57 74;91;61 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The PI-SDRMs with the lowest treatment/naive prevalence ratios were F53Y (5-fold), V82L (7-fold), M46L (9-fold), and I85V (14-fold). 2021 Viruses Result HIV F53Y;I85V;M46L;V82L 68;117;98;83 72;121;102;87 PI 4 6 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The prevalence of these seven mutations in NNRTI-experienced persons ranged from 0.1% for F227C to 8.1% for H221Y. 2021 Viruses Result HIV F227C;H221Y 90;108 95;113 NNRTI 43 48 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The SDRMs with the lowest treated/naive prevalence ratios were G190E (11-fold) and K103N (22-fold). 2021 Viruses Result HIV G190E;K103N 63;83 68;88 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The three candidate NRTI-SDRMs (T69deletion and K70Q/T) that increased in prevalence among NRTI-experienced persons were tenofovir-associated mutations. 2021 Viruses Result HIV K70Q;K70T 48;48 54;54 NRTI;NRTI 20;91 24;95 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Three additional tenofovir-associated mutations (K65N and K70G/N) did not increase in prevalence. 2021 Viruses Result HIV K65N;K70G;K70N 49;58;58 54;64;64 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Three mutations demonstrated a change in prevalence among RTI-naive persons: M41L, F77L, and T215D each decreased in prevalence. 2021 Viruses Result HIV F77L;M41L;T215D 83;77;93 87;81;98 RT 58 61 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Three of the mutations were on four expert lists including L10F, T74P, and L89V. 2021 Viruses Result HIV L10F;L89V;T74P 59;75;65 63;79;69 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Two of these mutations had relatively low treated/naive prevalence ratios including E138K (6-fold) and V179M (11-fold). 2021 Viruses Result HIV E138K;V179M 84;103 89;108 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Two SDRMS increased in prevalence among PI-experienced persons including V47A and I50L while 34 decreased in prevalence. 2021 Viruses Result HIV I50L;V47A 82;73 86;77 PI 40 42 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. V106M displayed the largest increase in prevalence, increasing from 2.6 to 9.1%. 2021 Viruses Result HIV V106M 0 5 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. With the exception of K65N, which was on four expert lists, the remaining tenofovir-associated mutations were on just one or two lists. 2021 Viruses Result HIV K65N 22 26 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. 3TC/EFV/TDF: 24.85%, n = 682), 5 patients (0.91%) treated with 3TC/AZT/EFV were infected with a K65R mutant, being this number significantly different (p < 0.001) from the 267 patients (39.15%) treated with 3TC/EFV/TDF combination. 2021 International journal of molecular sciences Result HIV K65R 96 100 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Also, comparing all patients revealed a significant association between 3TC/EFV/TDF and K65R (p < 0.001). 2021 International journal of molecular sciences Result HIV K65R 88 92 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Although its prevalence suffered a decrease between 2015 and 2016 (p = 0.0124), K65R prevailed the third most common SDRM in 2016 and 2017 (Figure 1). 2021 International journal of molecular sciences Result HIV K65R 80 84 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Despite the significant increased prevalence of the K65R in subtype C (11.26%, n = 347) viruses when compared with B (9.27%, n= 1305) subtype (p < 0.001, Supplementary Figure S2) we found probable events of K65R transmission also in subtype B viruses. 2021 International journal of molecular sciences Result HIV K65R;K65R 52;207 56;211 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Evidence for Transmission of K65R. 2021 International journal of molecular sciences Result HIV K65R 29 33 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Furthermore, the analysis of the clinical records from the individuals likely involved in K65R transmission supports this possibility for several cases showing a coincidence of geographic location, proximity in diagnostic dates and similar reported transmission routes (Supplementary Table S1). 2021 International journal of molecular sciences Result HIV K65R 90 94 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Having observed the clear increase in K65R along the studied yrs, we then decided to evaluate the ART combination schemes in use during the studied period (Figure 2), aiming at understanding ART usage impact on the SDRM. 2021 International journal of molecular sciences Result HIV K65R 38 42 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Importantly, K65R showed a clear rise along the years (Figure 1). 2021 International journal of molecular sciences Result HIV K65R 13 17 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. In contrast, K65R was only found in 0.37% (n = 15) of the viruses isolated from patients treated with 3TC/AZT/EFV vs. 2021 International journal of molecular sciences Result HIV K65R 13 17 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. In line with this hypothesis was the finding that viral loads for PLWH with K65R were significantly higher than for the rest of the cohort (180,739.60 +- 497,000.10 cop/mL vs. 2021 International journal of molecular sciences Result HIV K65R 76 80 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Interestingly, we found that K65R overlapping peptides were predicted to be recognized by two HLAs (HLA-A03, HLA-B58) in the wildtype version and by one additional HLA (HLA-B27) in the mutant version (Table 3). 2021 International journal of molecular sciences Result HIV K65R 29 33 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. K103N remained stable in the studied period. 2021 International journal of molecular sciences Result HIV K103N 0 5 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Overall, our results suggest that the presence of K65R mutation might contribute for the immune control of the virus in individuals harboring HLA-B27 possibly decreasing its transmission in populations with high prevalence of this HLA. 2021 International journal of molecular sciences Result HIV K65R 50 54 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Overall, the data strongly supports that, in contrast with other prevalent SDRM, K65R prevalence was increasing in Brazil, raising additional concerns about the efficacy of some of the ART combinations used. 2021 International journal of molecular sciences Result HIV K65R 81 85 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. SDRM in PR were found in 5021 (24.82%) sequences and the more frequent were V82A (9.99%, n = 2021), M46I (9.58%, n = 1938), and I54V (8.50%, n = 1719). 2021 International journal of molecular sciences Result HIV I54V;M46I;V82A 128;100;76 132;104;80 PR 8 10 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Similarly, all the other 10 most frequent SDRM followed a decreasing trend along the years with the remarkable exception for K65R and K103N (Figure 1). 2021 International journal of molecular sciences Result HIV K103N;K65R 134;125 139;129 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. The minimum spanning network analysis of these clusters (Figure 4) supports the occurrence of events of K65R transmission in the study cohort. 2021 International journal of molecular sciences Result HIV K65R 104 108 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. The most common mutation across the years was M184V (Figure 1), notwithstanding a decreasing trend and a significant decrease between 2015 (68.29%, n = 1874) and 2016 (53.21%, n = 2684) (p < 0.001) (Table 2). 2021 International journal of molecular sciences Result HIV M184V 46 51 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. The most common SDRM (Figure 1, Supplementary Table S2) were the substitutions in RT amino acids M184V (65.53%, n = 13,265), K103N (40.20%, n = 8738), and M41L (17.21%, n = 3480). 2021 International journal of molecular sciences Result HIV K103N;M184V;M41L 125;97;155 130;102;159 RT 82 84 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. The SDRM with most similar prevalence when comparing both groups were M46I, V82A, L90M and I54V. 2021 International journal of molecular sciences Result HIV I54V;L90M;M46I;V82A 91;82;70;76 95;86;74;80 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. This strong association of K65R with TDF containing schemes was found across HIV-1 subtypes (Supplementary Figure S1). 2021 International journal of molecular sciences Result HIV K65R 27 31 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. To investigate if the transmission of virus harboring K65R could have contributed to the increase in the prevalence of this mutation in Brazil, we performed a phylogenetic analysis on a subset of viral sequences including all the sequences with the K65R mutation and closely related sequences from public databases (Supplementary Figures S2 and S3). 2021 International journal of molecular sciences Result HIV K65R;K65R 54;249 58;253 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. We found K65R in at least two HIV-1 sequences in 21 well-delimited transmission clusters (16 from subtype B and 5 from subtype C) (Supplementary Table S1). 2021 International journal of molecular sciences Result HIV K65R 9 13 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. We performed artificial neural network-based predictions of binding to the globally most frequent class I HLAs of all the peptide sequences overlapping K65R and ranging from eight to 12 amino acids with the mutant or the wild-type residue. 2021 International journal of molecular sciences Result HIV K65R 152 156 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. We then used an immunoinformatic approach to investigate the predicted impact of K65R on immune-driven selective pressures. 2021 International journal of molecular sciences Result HIV K65R 81 85 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. While the prevalence of viruses harboring K103N increased between 2014 (40.97%, n = 1180) and 2015 (47.12%, n = 1293; p < 0.001) this was accompanied with a significant decrease in 2016 (42.53%, n = 2145; p < 0.001) and no significant difference between 2008 and 2017 (p = 0.919). 2021 International journal of molecular sciences Result HIV K103N 42 47 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Most frequent PI-RAMS were I85V, M46I, I50V and L90M (n=2, 5% each), all of them with modest impact in the activity of currently available PIs. 2021 Revista espanola de quimioterapia Result HIV I50V;I85V;L90M;M46I 39;27;48;33 43;31;52;37 PI;PI 14;139 16;142 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%), which confer high level resistance to efavirenz and nevirapine and intermediate to rilpivirine. 2021 Revista espanola de quimioterapia Result HIV G190A;G190E;G190S;K103N 49;49;49;28 58;58;58;33 NNRTI 12 17 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. Additionally, we have analyzed the distribution of the L74I polymorphism which was observed in 20 (11.5%) of the integrase sequences, being more prevalent in subtype A samples (n = 16, 94.1%) compared to 2.6% (n = 4) in subtype B (p < 0.0001) (supplemental table 3. 2021 Scientific reports Result HIV L74I 55 59 IN 113 122 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. As L74I variant was present in virtually all A6 sequences it was also observed within the identified clusters. 2021 Scientific reports Result HIV L74I 3 7 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. E157Q polymorphism was the most prevalent (9.8%) resistance associated variant in the analysed dataset and was notably more common among female individuals (n = 4, 50.0%) compared to 8.4% (n = 14) among males, p = 0.004. 2021 Scientific reports Result HIV E157Q 0 5 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. In subtype B one cluster with NNRTI K101H/E138A mutation was observed, in four sequence pairs there was also evidence of the shared resistance patterns (NRTI: D67N/K291Q and T215V, NNRTI: V106I, integrase: E157Q). 2021 Scientific reports Result HIV D67N;E138A;E157Q;K101H;K291Q;T215V;V106I 159;42;206;36;164;174;188 163;47;211;41;169;179;193 IN;NNRTI;NNRTI;NRTI 195;30;181;153 204;35;186;157 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. Transmitted drug resistance mutations (tDRM), based on WHO mutation list, were observed in one (0.6%) protease (L54M mutation), 6 (3.8%) NRTI (mutations in the codon positions: M41L, D67N, T215S/V, K219Q) and two (1.1%) (both E138K mutations) integrase sequences (supplemental table 2). 2021 Scientific reports Result HIV D67N;E138K;K219Q;L54M;M41L;T215S;T215V 183;226;198;112;177;189;189 187;231;203;117;181;196;196 IN;PR;NRTI 243;102;137 252;110;141 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. A less potent NAb, M1H2K1, was found from another mouse and exhibited similar sensitivity to a panel of BG505.T332N variants in the TZM-bl neutralization assays. 2021 mBio Result HIV T332N 110 115 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. All three NAbs neutralized the autologous tier 2 clade A BG505.T332N but not the tier 1 clade B SF162 or negative control, MLV. 2021 mBio Result HIV T332N 63 68 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. All trimer-binding MAbs, except M1H3K3, neutralized the autologous tier 2 BG505.T332N with up to a 63-fold difference in the half-maximal inhibitory concentration (IC50) value. 2021 mBio Result HIV T332N 80 85 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Among the four glycan hole mutations, Q130N did not affect HIV-1 neutralization by any of the three rabbit NAbs. 2021 mBio Result HIV Q130N 38 43 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Another NAb from M1, M1H3K3, neutralized heterologous strains but not autologous BG505.T332N. 2021 mBio Result HIV T332N 87 92 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Despite stronger Env binding, the single-cell-derived MAbs M4-Ab3 and M4-Ab9 neutralized BG505.T332N less effectively than the NGS-derived M4H2K1, with up to 4.6-fold-higher IC50 values. 2021 mBio Result HIV T332N 95 100 Env 17 20 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Glycan knockouts (KOs) at positions 276, 339, 392, and 398 and the S463R mutation exhibited only a negligible to modest effect, whereas glycan KOs at N355A, N363A, and N462A and the I396R mutation significantly reduced or completely abrogated neutralization by mouse NAbs. 2021 mBio Result HIV I396R;N355A;N363A;N462A;S463R 182;150;157;168;67 187;155;162;173;72 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. In contrast, S241N and P291T completely abrogated neutralization by RB35-1B11 and RB63-1E7 but not for the more potent RB63-4B5, whereas T465N significantly reduced the potency of RB63-4B5 (IC50 > 5.0 mug/ml), confirming that these three NAbs targeted glycan holes at positions 241/289 and 465 that were reported in previous rabbit studies. 2021 mBio Result HIV P291T;S241N;T465N 23;13;137 28;18;142 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Neutralization by three rabbit NAbs was tested in the TZM-bl assay against these BG505.T332N mutants, except for D230N/K232T, which was not included because of the low yield of pseudoparticles. 2021 mBio Result HIV D230N;K232T;T332N 113;119;87 118;124;92 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Of these NAbs, CP506 Fab targeted the C3/V4 region of HIV-1 Env and neutralized BG505.T332N with an IC50 of 0.1 mug/ml. 2021 mBio Result HIV T332N 86 91 Env 60 63 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Plasma neutralization against the four BG505.T332N mutants demonstrated that filling glycan holes could partially deplete neutralizing activity. 2021 mBio Result HIV T332N 45 50 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Rapid functional screening based on antibody yield and BG505.T332N neutralization resulted in three hits, one from RB35 and two from RB63. 2021 mBio Result HIV T332N 61 66 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. S1C) because immunoglobulin G (IgG) purified from the sera of these two mice neutralized BG505.T332N. 2021 mBio Result HIV T332N 95 100 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Six non-NAbs, three from each rabbit, were confirmed to be nonreactive with BG505.T332N in the TZM-bl assays. 2021 mBio Result HIV T332N 82 87 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. To verify these interactions, we created nine BG505.T332N variants (N276A, N339A, N355A, N363A, N462A, I396R, and S463R, along with N392A and N398A, which are in proximity to the binding site) and tested their neutralization by four of the newly identified mouse NAbs. 2021 mBio Result HIV I396R;N276A;N339A;N355A;N363A;N392A;N398A;N462A;S463R;T332N 103;68;75;82;89;132;142;96;114;52 108;73;80;87;94;137;147;101;119;57 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. We created a set of BG505.T332N Envs that had Q130N, D230N/K232T, S241N, P291T, and T465N mutations. 2021 mBio Result HIV D230N;K232T;P291T;Q130N;S241N;T465N;T332N 53;59;73;46;66;84;26 58;64;78;51;71;89;31 Env 32 36 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. We first assessed rabbit plasma at the last time point (week 30) against an expanded panel of viruses, including the respective autologous virus (either Du172.17 or Q842-d12), BG505.T332N, tier 1 SF162, and the 12-virus global panel, with MLV used as a control. 2021 mBio Result HIV T332N 182 187 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. We first assessed rabbit plasma at the last time point (week 30) against autologous tier 2 clade A BG505.T332N, tier 1 clade B SF162, and a global panel of 12 diverse isolates, with MLV included as a negative control. 2021 mBio Result HIV T332N 105 110 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Here, we subjected genes of IN variants to site-directed mutagenesis introducing D64V mutation to abrogate both LTR processing and joining activities deemed harmful to expressing cells, generating integrase variants IN_in_r1 and IN_in_r2 (Figure 1). 2021 Microorganisms Result HIV D64V 81 85 IN;LTR;IN 197;112;28 206;115;30 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. However, introduction of D64V led to a 2-fold decrease in protein stabilization by the lysosomal inhibitors, i.e., partially reversed the lysosomal re-routing (Figure 3b,c, Supplementary Figure S8b). 2021 Microorganisms Result HIV D64V 25 29 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Inactivation mutation D64V had no effect on the lysosomal degradation of the parental IN_a (Chl and individual inhibitors of lysosomal proteases had similar effect on IN_in as on IN_a; p > 0.05 in Mann-Whitney test; Figure 3c, Supplementary Figure S8b). 2021 Microorganisms Result HIV D64V 22 26 PR 135 144 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Introduction of inactivation mutation D64V led to a decrease in IFN-gamma, IL-2, and IFN-gamma/IL-2 production, with shrinkage of the spectrum of recognized epitopes (compare mice DNA immunized with IN_a to mice immunized with IN_in; Figure 9a-c). 2021 Microorganisms Result HIV D64V 38 42 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. The tests demonstrated that D64V mutation completely abrogated specific IN enzymatic activities (Supplementary Figure S5a,b; IN_in_r1 variant retained a non-specific exonuclease activity, Supplementary Figure S5c). 2021 Microorganisms Result HIV D64V 28 32 IN 72 74 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Thus, the loss of immunogenicity due to D64V mutation was restored by introduction of RAL resistance mutation patterns. 2021 Microorganisms Result HIV D64V 40 44 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Using this gene as a platform, we further designed IN variants harboring two sets of mutations conferring resistance to RAL, one with primary resistance mutation N155H and secondary mutations L74M, E92Q, V151I, G163R (IN_a_r1); and the other, with primary resistance mutation Q148K and secondary mutations E138K and G140S (IN_a_r2). 2021 Microorganisms Result HIV E138K;E92Q;G140S;G163R;L74M;N155H;Q148K;V151I 306;198;316;211;192;162;276;204 311;202;321;216;196;167;281;209 IN 51 53 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. High resistance level to NRTI class was verified in 85.3% (n = 70/82), being most of them 82.9% (n = 68/82) among those under 3TC use, and the M184I/V mutation was presented in all of them. 2021 BioMed research international Result HIV M184I;M184V 143;143 150;150 NRTI 25 29 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. In regard to NNRTI, high ARV resistance level was detected in approximately 90.0% of them, representing 64 of those 71 individuals who were taking EFV, and mutations K103N/S (71.8) and P225H (21.1%) were the most prevalent among them. 2021 BioMed research international Result HIV K103N;K103S;P225H 166;166;185 173;173;190 NNRTI 13 18 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. Only half of the individuals had used PI (n = 46/82), only 17% of individuals presented DRMs associated with protease inhibitors (n = 14), and the most frequent mutations were V82A/L/M (6/82; 7.3%) and I54L/M/V (5/82; 6%), L90M (4/82; 4.8%), and M46L/I (4/82; 4.8%) (Figure 1). 2021 BioMed research international Result HIV I54L;I54M;I54V;L90M;M46I;M46L;V82A;V82L;V82M 202;202;202;223;246;246;176;176;176 210;210;210;227;252;252;184;184;184 PR;PI 109;38 117;40 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. The most frequently detected DRMs were M184I/V (68/82; 82.9%), K70E/R (16/82; 19.5%), and T215F/Y (17/82; 20.7%) to NRTI and K103N/S (51/82; 62.1%), P225H (15/82; 18.2%), and V106A/I/M (11/82; 13.4%) to NNRTI (Figure 1). 2021 BioMed research international Result HIV K103N;K103S;K70E;K70R;M184I;M184V;P225H;T215F;T215Y;V106A;V106I;V106M 125;125;63;63;39;39;149;90;90;175;175;175 132;132;69;69;46;46;154;97;97;184;184;184 NNRTI;NRTI 203;116 208;120 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. Thymidine analog mutations (TAM) were detected in 35.4% of the individuals [17.1% (14/82) TAM-1 (including M41L, L210W, and T215Y) and 20.7% (17/82) TAM-2 (including D67N, K70R, T215F, and K219Q/E)]. 2021 BioMed research international Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 166;189;189;172;113;107;178;124 170;196;196;176;118;111;183;129 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. While analyzing the resistance profile of individuals with BCAR and BPAN variants, the heat map showed that the most frequent mutations in subtype B variants were M184I/V (NRTI) and K103N/S (NNRTI), and these also presented similar prevalence in both groups (Figure 2(a)). 2021 BioMed research international Result HIV K103N;K103S;M184I;M184V 182;182;163;163 189;189;170;170 NNRTI;NRTI 191;172 196;176 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. Eight TDF/FTC resistant strains were sporadic in the ML tree without obvious aggregation, but the other two CRF01_AE strains with K65R clustered together with 99% of the bootstrap value. 2021 BMC infectious diseases Result HIV K65R 130 134 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. K65R is known to confer high-level resistance to TDF and intermediate-level resistance to FTC, while M184I/V confers high-level resistance to FTC and 3TC and low-level resistance to abacavir (ABC). 2021 BMC infectious diseases Result HIV M184I;M184V;K65R 101;101;0 108;108;4 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. The mutations included K65R (61.5%, 8/13), M184I/V (38.5%, 5/13), and Y115F (2/13). 2021 BMC infectious diseases Result HIV K65R;M184I;M184V;Y115F 23;43;43;70 27;50;50;75 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. There was no significant correlation between the two CRF07_BC strains and K65K/R (data not shown). 2021 BMC infectious diseases Result HIV K65K;K65R 74;74 80;80 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. Y115F can confer high-level resistance to ABC and only low-level resistance to TDF (Table 1). 2021 BMC infectious diseases Result HIV Y115F 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. Among them, 9 cases were protease inhibitor-related resistance, and the main resistance sites were L33F, V82A, Q58E, M46L, M46I; There were 4 cases of nucleoside reverse transcriptase inhibitor resistance, the main mutation sites were V75VI, K219Q, T215A, K65R; There were 5 cases of non-nucleoside reverse transcriptase inhibitor resistance, the main mutation sites were V179E, A98G, V106I, Y181C, G190S, V179D. 2021 Medicine Result HIV A98G;G190S;K219Q;K65R;L33F;M46I;M46L;Q58E;T215A;V106I;V179D;V179E;V75I;V75V;V82A;Y181C 379;399;242;256;99;123;117;111;249;385;406;372;235;235;105;392 383;404;247;260;103;127;121;115;254;390;411;377;240;240;109;397 NNRTI;NRTI;PR 284;151;25 320;183;33 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. The HIV-1 resistance mutation that enters the network is protease inhibitor-related resistance, which contains 3 nodes, and the mutation sites are L33F and Q58E. 2021 Medicine Result HIV L33F;Q58E 147;156 151;160 PR 57 65 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Accordingly, the Y99H mutation may alter pocket shape to indirectly modulate IN-STP0404 binding. 2021 PLoS pathogens Result HIV Y99H 17 21 IN 77 79 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. As shown in Fig 2, the viral population collected at passage 14, which contained both Y99H and A128T changes, was 61.4-fold less susceptible compared to wild type HIV-189.6, while the passage 4 viruses were about 5.5 times less susceptible. 2021 PLoS pathogens Result HIV A128T;Y99H 95;86 100;90 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. As shown in Fig 2, Y99H was initially selected at comparatively low STP0404 concentration at passage 2, and was detected in 90% of the sequenced IN clones at passage 10. 2021 PLoS pathogens Result HIV Y99H 19 23 IN 145 147 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. As shown in Fig 3A, while the single A128T mutant replicated like wild type, Y99H and Y99H/A128T mutant viruses yielded 35 and 70-fold less p24, respectively, at day 4 post-infection, suggesting that Y99H significantly impaired HIV-1 replication kinetics. 2021 PLoS pathogens Result HIV A128T;A128T;Y99H;Y99H;Y99H 37;91;77;86;200 42;96;81;90;204 p24 140 143 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. At passage 10, the A128T change was partially detected (90 and 40%) in both selection cultures together with Y99H. 2021 PLoS pathogens Result HIV A128T;Y99H 19;109 24;113 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. For this, we constructed molecular clones of HIV-189.6 containing Y99H alone, A128T alone, and both Y99H and A128T IN changes. 2021 PLoS pathogens Result HIV A128T;A128T;Y99H;Y99H 78;109;66;100 83;114;70;104 IN 115 117 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. However, when STP0404 concentration were further elevated, all 40 sequenced IN clones in both cultures contained both Y99H and A128T (passage 14). 2021 PLoS pathogens Result HIV A128T;Y99H 127;118 132;122 IN 76 78 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Next, we determined the X-ray structure of the HIV-1 IN catalytic core domain (CCD) (F185H) in complex with STP0404 at 2.2 A resolution (S1 Table). 2021 PLoS pathogens Result HIV F185H 85 90 IN 53 55 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. This putative Y99H-based structural change would appear to underlie viral resistance to STP0404 at comparatively low inhibitor concentrations, whereas higher levels of resistance require both A128T and Y99H changes. 2021 PLoS pathogens Result HIV A128T;Y99H;Y99H 192;14;202 197;18;206 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Because genotypic resistance tests for INIs were not available for a substantial number of patients (648 of 669, 96.8%), no association between INI-RAMs and VF could be assessed; a minor mutation was detected (T97A) in only 3 patients in a previous genotypic test, including 1 patient who subsequently experienced VF. 2021 Open forum infectious diseases Result HIV T97A 210 214 IN;IN 39;144 43;147 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. In contrast (Cox model 3), the presence of M184V/I (versus its absence; adjusted hazard ratio [aHR], 3.31; 95% CI, 1.02-10.74; P = .046) and, particularly (Cox model 5), the combination of M184V/I plus at least 1 TAM (versus no M184V/I plus TAMs; aHR, 4.63; 95% CI, 1.19-17.94; P = .027) predicted time to VF. 2021 Open forum infectious diseases Result HIV M184I;M184I;M184I;M184V;M184V;M184V 228;43;189;228;43;189 235;50;196;235;50;196 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Since a potential interaction between time of virological suppression at baseline and RAMs has been previously suggested, a sensitivity analysis was performed to estimate the effect of M184V/I with and without TAMs in the subgroups of patients with <=7 and >7 years of virological suppression (median value in our population). 2021 Open forum infectious diseases Result HIV M184I;M184V 185;185 192;192 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Starting from a model that included risk factor for HIV infection, age, detectable HIV-RNA at baseline, presence of TAMs at last GRT, nadir CD4 and zenith HIV-RNA, viral subtype and HIV-RNA at last GRT, time of virological suppression, and previous VF with an INI-containing regimen, the presence of any NRTIs-RAM (Cox model 1) was not predictive of VF, and this variable was therefore excluded from the model (P = .118); similarly, the presence of at least 1 TAM (Cox model 2) and the presence of M184V/I in the absence of TAMs (Cox model 4) were not associated with the outcome (P = .243 and P = .693, respectively). 2021 Open forum infectious diseases Result HIV M184I;M184V 498;498 505;505 NRTI;IN 304;260 309;263 HIV infections 52 65 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. The effect size of M184V/I with and without TAMs on VF was also estimated: compared with patients with no RAMs, those harboring a virus with the M184V/I but no TAMs had no increased risk of VF (aHR, 1.88; 95% CI, 0.23-15.07; P = .554), whereas the association of M184V/I and at least 1 TAM confirmed a significant association with the outcome (aHR, 4.40; 95% CI, 1.12-17.24; P = .034), after adjusting for previous VF with INIs (aHR, 6.03; 95% CI, 1.29-28.25; P = .023) and time of virological suppression (>2 versus <=2 years; aHR, 0.27; 95% CI, 0.09-0.82; P = .021). 2021 Open forum infectious diseases Result HIV M184I;M184I;M184I;M184V;M184V;M184V 19;145;263;19;145;263 26;152;270;26;152;270 IN 423 427 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Whereas in the group with longer time of virological control no association between RAMs and outcome was detected, patients with shorter duration of virological suppression had a higher risk of VF when M184V/I and TAMs were simultaneously present (compared with absence of RAMs; aHR, 11.56; 95% CI, 2.22-60.08; P = .004), but not when M184V/I was present without TAMs (compared with absence of RAMs; aHR, 4.90; 95% CI, 0.58-41.79; P = .146). 2021 Open forum infectious diseases Result HIV M184I;M184I;M184V;M184V 202;335;202;335 209;342;209;342 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. Among the NRTI DRMs, M184I/V (42.2%, 166/393) was the most frequent, followed by K65R (27.2%, 107/393). 2021 Infection and drug resistance Result HIV K65R;M184I;M184V 81;21;21 85;28;28 NRTI 10 14 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. One case (0.3%, 1/393) carried PI-related DRMs, K20T, M46I, and K43T. 2021 Infection and drug resistance Result HIV K20T;K43T;M46I 48;64;54 52;68;58 PI 31 33 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. The major NNRTI DRMs were V179D/E (37.9%, 149/393), V106I/M (25.7%, 101/393), and K103N/Q (25.2%, 99/393) (Table 3). 2021 Infection and drug resistance Result HIV K103N;K103Q;V106I;V106M;V179D;V179E 82;82;52;52;26;26 89;89;59;59;33;33 NNRTI 10 15 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. The most common NRTI mutation pattern was M184V+K65R, with a frequency of 15.0% (59/393). 2021 Infection and drug resistance Result HIV K65R;M184V 48;42 52;47 NRTI 16 20 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. Altogether, 68 participants with baseline NRTI resistance (including 50 with M184V/I) received B/F/TAF during the study and had postswitch virologic data. 2021 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V 77;77 84;84 NRTI 42 46 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. Among participants with M184V or I mutations at baseline 97% (30 of 31) on B/F/TAF and 95% (19 of 20) on SBR had HIV-1 RNA <50 copies/mL at week 24. 2021 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 24 29 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. At baseline, 13% (44 of 328) in the B/F/TAF group and 16% (26 of 165) in the SBR group had NRTI resistance, including 9% (31 of 328) and 12% (20 of 165) with M184V/I mutations in the B/F/TAF and SBR groups, respectively. 2021 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V 158;158 165;165 NRTI 91 95 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. One participant with M184V on B/F/TAF discontinued after the baseline visit and did not have virologic data at week 24. 2021 Journal of acquired immune deficiency syndromes (1999) Result HIV M184V 21 26 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. The median age overall was 49 years, 32% were ciswomen, 2% transwomen, and 10% had documented baseline M184V/I mutation. 2021 Journal of acquired immune deficiency syndromes (1999) Result HIV M184I;M184V 103;103 110;110 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. Two participants were found to have baseline INSTI resistance based on historical genotype data and were excluded from the primary analysis because of this protocol violation; 1 participant each with Y143C and Q148K mutations, both were randomized to B/F/TAF and had HIV-1 RNA <50 copies/mL at week 24. 2021 Journal of acquired immune deficiency syndromes (1999) Result HIV Q148K;Y143C 210;200 215;205 INSTI 45 50 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. 2E, p = 0.4331), suggesting that HIV-1K359A/T371I either does not require IP6 for replication, or that the T371I mutation rescues both replication and IP6 incorporation. 2021 Retrovirology Result HIV T371I;T371I 44;107 49;112 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Addition of the T371I substitution to HIV-1K359A restored infectious virion yield to wild-type levels. 2021 Retrovirology Result HIV T371I 16 21 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Although this second-site, apparently compensatory change was identified only in the context of HIV-1K359A, we asked whether the T371I substitution could rescue the HIV-1K290A, given purported similar roles of K290 and K359 in binding IP6. 2021 Retrovirology Result HIV T371I 129 134 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Because HIV-1K359A/T371I is fully infectious despite encoding a mutation that is predicted to diminish IP6 packaging into virions, we next asked whether HIV-1K359A/T371I requires IP6 in target cells to be maximally infectious. 2021 Retrovirology Result HIV T371I;T371I 19;164 24;169 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Because the HIV-1K359A is defective for IP6 binding we next asked whether HIV-1K359A/T371I retained infectiousness when cellular IP6 levels were reduced. 2021 Retrovirology Result HIV T371I 85 90 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. HIV-1T371I replicated poorly in CEM cells but well in MT4 cells, perhaps reflecting the greater permissiveness of MT4 cells. 2021 Retrovirology Result HIV T371I 5 10 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Importantly however, we found similar phenotypes for HIV-1K359A/T371I in spreading replication assays in both MT4 and CEM cells; namely, addition of the T371I substitution to HIV-1K359A restored replication, with the HIV-1K359A/T371I double mutant exhibiting only a modest delay compared to HIV-1WT in both cell types. 2021 Retrovirology Result HIV T371I;T371I;T371I 64;153;228 69;158;233 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Importantly, the yield of HIV-1K359A/T371I was only marginally reduced compared to wild type HIV-1 and there was no difference in yield of infectious HIV-1K359A/T371I from WT 293T cells versus IPMK deficient 293T cells. 2021 Retrovirology Result HIV T371I;T371I 37;161 42;166 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Importantly, we see the same phenotype for particle production as we do with infectivity assays: production of HIV-1WT particles is impaired in IPMK KO cells, but there are no production deficits for HIV-1K359A, HIV-1T371I, or HIV-1K359A/T371I. 2021 Retrovirology Result HIV T371I 238 243 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Indeed, we found that HIV-1K290A/T371I, unlike HIV-1K290A, yielded similar levels of infectious HIV-1 virions to wild-type HIV-1. 2021 Retrovirology Result HIV T371I 33 38 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Infection of target cells with impaired IP6 synthesis by HIV-1WT or HIV-1K359A/T371I. 2021 Retrovirology Result HIV T371I 79 84 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Infectious HIV-1K359A/T371I particle yield is not affected by reduction of IP6 synthesis in virus producing cells. 2021 Retrovirology Result HIV T371I 22 27 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Moreover, there was no deficit in the infectiousness of HIV-1K359A/T371I in WT or IPMK-deficient MT4 target cells. 2021 Retrovirology Result HIV T371I 67 72 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Notably, The T371I mutation identified herein had been described previously in a different context. 2021 Retrovirology Result HIV T371I 13 18 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. To determine whether the effects of the T371I mutant were evident outside the context of transfected 293T cells, we performed spreading replication assays of HIV-1WT, HIV-1T371I, HIV-1K359A, and HIV-1K359A/T371I in MT4 cells. 2021 Retrovirology Result HIV T371I;T371I 40;206 45;211 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. To determine whether the T371I mutant rescued the infectivity defect present in HIV-1K359A, we generated a proviral clone, HIV-1K359A/T371I, encoding both mutations and measured the infectious virion yield from proviral plasmid-transfected 293T cells. 2021 Retrovirology Result HIV T371I;T371I 25;134 30;139 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. We generated twelve IPMK-deficient MT4 target cell clones and six control clones and performed single cycle infection assays using HIV-1WT and HIV-1K359A/T371I. 2021 Retrovirology Result HIV T371I 154 159 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Yield of HIV-1T371I was also slightly reduced compared to wildtype but not impacted by IPMK deficiency. 2021 Retrovirology Result HIV T371I 14 19 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. Among ART naive individuals, 15 (30%) had drug resistance mutations (DRM); the most common of which were the Reverse Transcriptase (RT):E138A (8.0%) and RT:K219Q (8.0%) mutations. 2021 Frontiers in microbiology Result HIV E138A;K219Q 134;156 141;161 RT;RT;RT 109;132;153 130;134;155 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. Among the 78 sequences from the Larkana outbreak with prevalent drug resistance mutations, the DRM RT:K219Q was shared between five sequences whereof all clustered together in cluster_CRF02_AG_1 (Tables 2, 3). 2021 Frontiers in microbiology Result HIV K219Q 102 107 RT 99 101 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. Among treatment-experienced individuals, the most common mutations were RT:E138A (12.92%), RT:K219Q (8.86%), and RT:K103N (6.64%). 2021 Frontiers in microbiology Result HIV E138A;K103N;K219Q 75;116;94 80;121;99 RT;RT;RT 72;91;113 74;93;115 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. Similarly, DRM PI:N88D, associated with resistance against protease inhibitors (PI), such as atazanavir/ritonavir, and tipranavir/ritonavir was observed in two treatment-experienced participants, while DRMs PI:M46L, PI:D30N, PI:N83D, PI:K43T, PI:G73S, PI:L33F were seen in one treatment-experienced individual each (Table 3). 2021 Frontiers in microbiology Result HIV D30N;G73S;K43T;L33F;M46L;N83D;N88D 219;246;237;255;210;228;18 223;250;241;259;214;232;22 PR;PI;PI;PI;PI;PI;PI;PI;PI 59;15;80;207;216;225;234;243;252 67;17;82;209;218;227;236;245;254 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. The DRM RT:E138A was found in 38 sequences of different subtypes including 21 sequences in cluster_A1_1, three sequences in cluster A1_2, seven sequences in cluster_CRF02_AG_1, one sequence in cluster_CRF02AG_2, and six sequences that were not part of a cluster. 2021 Frontiers in microbiology Result HIV E138A 11 16 RT 8 10 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. The DRM RT:K103N was found among 21 sequences, whereof 19 sequences were found in cluster (cluster_CRF02_AG_1). 2021 Frontiers in microbiology Result HIV K103N 11 16 RT 8 10 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. The DRM RT:M184V was found in two sequences - both in cluster_CRF02_AG_1. 2021 Frontiers in microbiology Result HIV M184V 11 16 RT 8 10 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. The DRM RT:V179L was distributed among 10 sequences in cluster_CRF02AG_1, and two sequences in cluster_CRF02AG_2 (Tables 2, 3). 2021 Frontiers in microbiology Result HIV V179L 11 16 RT 8 10 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. The DRMs RT:E138A and RT:K103N confer resistance against non-nucleoside reverse transcriptase inhibitors (NNRTI) rilpivirine and efavirenz, respectively, while RT:K219Q is associated with resistance against nucleoside reverse transcriptase inhibitors (NRTI) zidovudine. 2021 Frontiers in microbiology Result HIV E138A;K103N;K219Q 12;25;163 17;30;168 NNRTI;NRTI;NNRTI;NRTI;RT;RT;RT 57;207;106;252;9;22;160 93;239;111;256;11;24;162 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. K103N (0.42%, 10/2368), Y181C (0.21%, 5/2368), and G190A (0.21%, 5/2368) were the most common NRTI-associated mutations, and M184V (0.21%, 5/2368), L210W (0.21%, 5/2368), and T215S (0.13%, 3/2368) were the most common NNRTI-associated mutations. 2021 Virology journal Result HIV G190A;L210W;M184V;T215S;Y181C;K103N 51;148;125;175;24;0 56;153;130;180;29;5 NNRTI;NRTI 218;94 223;98 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. M46L (0.17%, 4/2368) was the most prevalent mutation in the protease region. 2021 Virology journal Result HIV M46L 0 4 PR 60 68 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. We also observed that 28.85% (15/52) of patients with TDR were included in 9 clusters, and an analysis of shared mutations revealed that cluster C contained two TDR sequences with the K103N mutation. 2021 Virology journal Result HIV K103N 184 189 34534138 Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection. After week 144, the sponsor was notified that a local laboratory had performed genotypic resistance testing at the investigator's discretion using samples collected ~1 week after the week 132 visit, revealing the NRTI resistance mutation M184V. 2022 AIDS (London, England) Result HIV M184V 238 243 NRTI 213 217 34534138 Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection. M184V was detected at week 132 and R263R/K was detected at week 144 in one participant in the DTG + 3TC group. 2022 AIDS (London, England) Result HIV R263K;R263R;M184V 35;35;0 42;42;5 34534138 Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection. The central laboratory initiated resistance testing using samples from the week 132 and 144 visits: M184V at week 132 (SVW criteria time point) was confirmed; at week 144, both M184V and the DTG resistance-associated mutation mixture R263R/K were detected, the latter conferring a 1.8-fold change in susceptibility to DTG. 2022 AIDS (London, England) Result HIV M184V;M184V;R263K;R263R 100;177;234;234 105;182;241;241 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. A minor band was detected in all samples (but strongest in the E180C virions under reducing conditions) at approximately 43KDa. 2021 PLoS pathogens Result HIV E180C 63 68 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. A similar pattern was seen in the membrane fraction (S3C and S3E Fig), except that there was noticeably more CA detected here following infection with A14C/E45C VLP compared to WT VLP. 2021 PLoS pathogens Result HIV A14C;E45C 151;156 155;160 Capsid 109 111 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Alternatively, as the nuclear envelope marker, lamin B1, was also distributed in these two fractions, it could be hypothesised that A14C/E45C was accumulating at the nuclear envelope rather than inside the nucleus. 2021 PLoS pathogens Result HIV A14C;E45C 132;137 136;141 Env;Env 30;174 38;182 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Although P207C/T216C and the V181C mutants appeared more stable than WT at 2 hpi, they were not more stable at 20 hpi (Fig 2C), suggesting that neither of these mutants had increased viral core stability compared to WT. 2021 PLoS pathogens Result HIV P207C;T216C;V181C 9;15;29 14;20;34 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Although the levels of IN were similar between WT and A14C/E45C at each time point, there was more A14C/E45C CA than WT CA present until 30 hpi, again confirming the increased stability of the mutant CA. 2021 PLoS pathogens Result HIV A14C;A14C;E45C;E45C 54;99;59;104 58;103;63;108 IN;Capsid;Capsid;Capsid 23;109;120;200 25;111;122;202 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Although there was some variation in protein levels between different time points, importantly, the total levels of both CA and IN in whole cell lysates were similar between WT and A14C/E45C (CC) infection at all time points (Figs 6A and S3). 2021 PLoS pathogens Result HIV A14C;E45C 181;186 185;190 IN;Capsid 128;121 130;123 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Analysis of the number of foci per cell showed that there was increased A14C/E45C foci compared to WT infections at all time points (Fig 7E). 2021 PLoS pathogens Result HIV A14C;E45C 72;77 76;81 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Apart from the inter-hexamer P207C/T216C mutant that showed similar infectivity to WT, the remainder of the mutants also showed decreased infectivity, ranging from ~0.05-10% of WT infectivity. 2021 PLoS pathogens Result HIV P207C;T216C 29;35 34;40 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. As equal numbers of cores were arriving at the nucleus, as measured by CA-NUP358 staining (Fig 7B), this suggests that the A14C/E45C cores were spending more time at the nuclear pore. 2021 PLoS pathogens Result HIV A14C;E45C 123;128 127;132 Capsid 71 73 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. As expected, the A14C/E45C/W184A/M185A and W184A/M185A mutants that weaken CTD-CTD interactions were severely impaired for virus production (S1A Fig). 2021 PLoS pathogens Result HIV A14C;E45C;M185A;W184A;M185A;W184A 17;22;33;27;49;43 21;26;38;32;54;48 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. As observed previously, the P38A mutant that had reduced CA lattice stability had a marked reduction in GFP expression in all the cell lines (Fig 3, grey bars). 2021 PLoS pathogens Result HIV P38A 28 32 Capsid 57 59 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. As seen before, infection with mutant P38A resulted in less accumulation of viral cDNA (Fig 4A, grey lines). 2021 PLoS pathogens Result HIV P38A 38 42 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. CA protein from the A14C/E45C mutant is detected in nuclear and chromatin fractions. 2021 PLoS pathogens Result HIV A14C;E45C 20;25 24;29 Capsid 0 2 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Conversely, IN levels decreased markedly between 8 and 24 hpi, suggesting that IN protein has a shorter half-life than CA, but this was observed for both WT and A14C/E45C samples (S3B and S3D Fig). 2021 PLoS pathogens Result HIV A14C;E45C 161;166 165;170 IN;IN;Capsid 12;79;119 14;81;121 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Counting the number of foci per cell (Fig 7B) revealed that there were similar levels of interaction between CA and NUP358 throughout the time course of infection, and there was no significant difference between WT and A14C/E45C infections. 2021 PLoS pathogens Result HIV A14C;E45C 219;224 223;228 Capsid 109 111 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Finally, we were able to detect low levels of A14C/E45C CA in the chromatin fractions as early as 30 minutes post infection (Figs 6E and S3G). 2021 PLoS pathogens Result HIV A14C;E45C 46;51 50;55 Capsid 56 58 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Furthermore, both CA and IN from A14C/E45C mutant VLP infections were detected in the nuclear and chromatin fractions of aphidicolin-treated cells at similar levels to the untreated cells (S4E and S4F Fig). 2021 PLoS pathogens Result HIV A14C;E45C 33;38 37;42 IN;Capsid 25;18 27;20 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. HeLa cells were synchronously infected with equal RT units of WT or A14C/E45C VLP and cells were harvested at either 0, 0.5 and 2 hpi or at 4, 8, 24 and 30 hpi in different experiments. 2021 PLoS pathogens Result HIV A14C;E45C 68;73 72;77 RT 50 52 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. HeLa cells were synchronously infected with equal RT units of WT or A14C/E45C VLP for 2, 4, 6, 8 and 10 hpi. 2021 PLoS pathogens Result HIV A14C;E45C 68;73 72;77 RT 50 52 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. HeLa cells were synchronously infected with equal RT units of WT, A14C/E45C, E180C or M68C/E212C VLP. 2021 PLoS pathogens Result HIV A14C;E180C;E212C;E45C;M68C 66;77;91;71;86 70;82;96;75;90 RT 50 52 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. However, recently, it has been observed that CPSF6 only redistributes to nuclear speckles during WT HIV-1 infection and not during infection with CPSF6-binding deficient mutants A77V and N74D. 2021 PLoS pathogens Result HIV A77V;N74D 178;187 182;191 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. However, the hyper-stable mutants A14C/E45C and M68C/E212C had a different phenotype. 2021 PLoS pathogens Result HIV A14C;E212C;E45C;M68C 34;53;39;48 38;58;43;52 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. In addition, the P38A mutant was included in the panel as a negative control, as it has shown to be less stable than WT. 2021 PLoS pathogens Result HIV P38A 17 21 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. In agreement with previous reports, we recovered much less CA in the pellet fraction than the supernatant fraction from cells infected with the negative hypo-stable control, P38A. 2021 PLoS pathogens Result HIV P38A 174 178 Capsid 59 61 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. In contrast, mutant M68C/E212C VLP only produced ~10% of the cDNA of WT, and there was a further reduction in the amount of 2-LTR circles, to <1% of that produced by WT VLP. 2021 PLoS pathogens Result HIV E212C;M68C 25;20 30;24 LTR 126 129 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. In contrast, there were clear differences in the staining for CA-NUP153 co-localisation between WT and A14C/E45C infections (Fig 7D-7F). 2021 PLoS pathogens Result HIV A14C;E45C 103;108 107;112 Capsid 62 64 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. In every cell line, the M68C/E212C mutant was the most severely impaired at each replication stage. 2021 PLoS pathogens Result HIV E212C;M68C 29;24 34;28 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. In order to investigate nuclear entry of the A14C/E45C mutant further, we monitored the interactions between CA and the nuclear pore proteins NUP358 and NUP153 during infection. 2021 PLoS pathogens Result HIV A14C;E45C 45;50 49;54 Capsid 109 111 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Interestingly, as well as being only slightly defective for reverse transcription, both A14C/E45C and E180C mutant VLP were able to produce ~20% the amount of 2-LTR circles produced by WT VLP. 2021 PLoS pathogens Result HIV A14C;E180C;E45C 88;102;93 92;107;97 RT;LTR 60;161 81;164 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Interestingly, the M68C/E212C appeared to be the most stable mutant in our fate of CA assays (Fig 2). 2021 PLoS pathogens Result HIV E212C;M68C 24;19 29;23 Capsid 83 85 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Likewise, the P207C/T216C mutant had similar infectivity to WT VLP and had similar levels of reverse transcription (Fig 4B, red lines). 2021 PLoS pathogens Result HIV P207C;T216C 14;20 19;25 RT 93 114 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Moreover, comparing the localisation of the VLP showed that the A14C/E45C foci appeared to localise more towards the cytoplasmic side of the DAPI edge while the WT foci were mainly on the nuclear side (Fig 7F). 2021 PLoS pathogens Result HIV A14C;E45C 64;69 68;73 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Of note, the inter-hexamer mutants V181C, L151C/L189C and K203C/A217C were partially impaired for VLP production (S1A Fig), likely due to the importance of this interface on virus assembly. 2021 PLoS pathogens Result HIV A217C;K203C;L151C;L189C;V181C 64;58;42;48;35 69;63;47;53;40 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Of the three hyper-stable mutants, A14C/E45C, M68C/E212C and E180C (Fig 3, black arrowheads), the infectivity ranged from 0.7-4%, 0.07-0.4% and 2-10% respectively between the different cell lines. 2021 PLoS pathogens Result HIV A14C;E180C;E212C;E45C;M68C 35;61;51;40;46 39;66;56;44;50 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Surprisingly, despite a ~95% decrease in infectivity, A14C/E45C reverse transcribed to WT levels (Fig 4C, blue lines) and mutant M68C/E212C still produced about 10% the cDNA of WT (Fig 4D, orange lines), even though its infectivity was reduced to less than 1% (Fig 3). 2021 PLoS pathogens Result HIV A14C;E212C;E45C;M68C 54;134;59;129 58;139;63;133 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The A14C/E45C mutant is impeded at nuclear entry. 2021 PLoS pathogens Result HIV A14C;E45C 4;9 8;13 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The association of A14C/E45C CA with nuclear fractions, particularly with the chromatin-bound fraction, suggests that, despite being hyper-stable, this CA protein could enter the nucleus. 2021 PLoS pathogens Result HIV A14C;E45C 19;24 23;28 Capsid;Capsid 29;152 31;154 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The E180C and V181C mutants showed WT levels of strong stop cDNA, A204C accumulated about 10% the cDNA of WT and A42C/T54C and Q63C/Y169C only accumulated ~1% the cDNA of WT. 2021 PLoS pathogens Result HIV A204C;A42C;E180C;Q63C;T54C;V181C;Y169C 66;113;4;127;118;14;132 71;117;9;131;122;19;137 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The localisation of these foci (Fig 7C) seemed to be similarly around the DAPI edge for both VLP, but with a tendency for WT foci to be further into the nucleus than A14C/E45C foci. 2021 PLoS pathogens Result HIV A14C;E45C 166;171 170;175 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The new mutants E180C, L151C/L189C and K203C/A217C were designed based on a previous report demonstrating that disulphide bonds can have a variable Cbeta-Cbeta inter-residue spacing of between 3.5-4.5A. 2021 PLoS pathogens Result HIV A217C;E180C;K203C;L151C;L189C 45;16;39;23;29 50;21;44;28;34 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The original mutant used to determine the crystal structure of a hexameric CA assembly, A14C/E45C/W184A/M185A, was also included as a negative control. 2021 PLoS pathogens Result HIV A14C;E45C;M185A;W184A 88;93;104;98 92;97;109;103 Capsid 75 77 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. There was no further decrease in integration compared to the levels of 2-LTR circles, suggesting that the M68C/E212C mutant is more severely impaired earlier in replication than the other two hyper-stable mutants and is blocked for nuclear entry. 2021 PLoS pathogens Result HIV E212C;M68C 111;106 116;110 LTR 73 76 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. This may reflect a stronger association of A14C/E45C CA with the plasma membrane or organelle membranes that are both connected to microtubules which bind CA, or perhaps increased association with the nuclear membrane as this is continuous with the ER which is detected in this fraction. 2021 PLoS pathogens Result HIV A14C;E45C 43;48 47;52 Capsid;Capsid 53;155 55;157 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. This suggests that there is little difference in the early stages of infection, up to reaching the nuclear pore, between WT and A14C/E45C VLP, and, once again, that cores reach the nucleus within 2 hpi, sooner than previously expected. 2021 PLoS pathogens Result HIV A14C;E45C 128;133 132;137 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Three mutants showed this phenotype: M68C/E212C, A14C/E45C and E180C (Fig 2C, black arrows and highlighted with dashed boxes in Fig 2A). 2021 PLoS pathogens Result HIV A14C;E180C;E212C;E45C;M68C 49;63;42;54;37 53;68;47;58;41 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Thus, based on these results, the L151C/L189C and the K203C/A217C mutants as well as the A14C/E45C/W184A/M185A and W184A/M185A mutants were not included in further experiments. 2021 PLoS pathogens Result HIV A14C;E45C;M185A;W184A;A217C;K203C;L151C;L189C;M185A;W184A 89;94;105;99;60;54;34;40;121;115 93;98;110;104;65;59;39;45;126;120 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Thus, being on the cytoplasmic side of the DAPI staining, together with increased CA-NUP153 staining, suggests that A14C/E45C hyper-stable cores are being trapped at the NPC. 2021 PLoS pathogens Result HIV A14C;E45C 116;121 120;125 Capsid 82 84 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Unexpectedly, there was more IN present in the chromatin fraction from the WT infections than the A14C/E45C infections at all time points (Figs 6E and S3G). 2021 PLoS pathogens Result HIV A14C;E45C 98;103 102;107 IN 29 31 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. We therefore decided to focus on the A14C/E45C, E180C and M68C/E212C mutants to investigate the effect of core stability on the other early replication steps. 2021 PLoS pathogens Result HIV A14C;E180C;E212C;E45C;M68C 37;48;63;42;58 41;53;68;46;62 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Whilst we confirmed that expression of these mutant capsid proteins in 293T producer cell lysates was similar to WT VLP (S1C Fig), we detected an additional, smaller, CA band for both L151C/L169C and K203/A217C. 2021 PLoS pathogens Result HIV A217C;L151C;L169C 205;184;190 210;189;195 Capsid;Capsid 52;167 58;169 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. In particular, two TCs contained shared DRMs of E138G + V179E and V106I + V179D in Baise and Qinzhou cities, respectively. 2021 Frontiers in genetics Result HIV E138G;V106I;V179D;V179E 48;66;74;56 53;71;79;61 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. More remarkably, a man who have sex with man (MSM) from Baise city and a male HET from Qinzhou city comprised a transmission network, both of which were subtype CRF55_01B, showing DRM sharing for V179E. 2021 Frontiers in genetics Result HIV V179E 196 201 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. The largest PDR-related cluster within network contained DRM propagation of E138A, V82VF, V179D, V179VD, and V106I, while the remaining two PDR-related clusters are only involved in V106I propagation. 2021 Frontiers in genetics Result HIV E138A;V106I;V106I;V179D;V179D;V179V;V82F;V82V 76;109;182;97;90;97;83;83 81;114;187;103;95;103;88;88 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. The most prevalent shared DRM was V106I (45.35%, 24/53), followed by V179D (15.1%, 8/53), and V179E (15.1%, 8/53). 2021 Frontiers in genetics Result HIV V106I;V179D;V179E 34;69;94 39;74;99 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. V106I (4.0%, 41/1,025) and V179D (3.8%, 39/1,025) were the most common DRMs, followed by V179E (2.7%, 28/1,025) (Figure 1B). 2021 Frontiers in genetics Result HIV V179D;V179E;V106I 27;89;0 32;94;5 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. No PIs RAMs were observed, whereas three accessory INSTI-selected mutations T97A (n = 1), E157Q (n = 2), and G163R (n = 1), which have minimal effect on INSTI susceptibility, were observed in four pregnant women. 2021 Genes Result HIV E157Q;G163R;T97A 90;109;76 95;114;80 INSTI;INSTI;PI 51;153;3 56;158;6 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. Polymorphic accessory INSTI-selected mutations, which have minimal effect on INSTI susceptibility were observed in 8 children/adolescents, as follows: T97A (n = 2), E157Q (n = 5), and S230SR (n = 1). 2021 Genes Result HIV E157Q;S230R;S230S;T97A 165;184;184;151 170;190;190;155 INSTI;INSTI 22;77 27;82 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. The combination mutation I54V+V82A confers intermediate resistance to all the currently approved PIs with the exception of darunavir, which retains full activity. 2021 Genes Result HIV I54V;V82A 25;30 29;34 PI 97 100 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. The most prevalent RT RAMs among children and adolescents and their relative proportions were as follows: M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), V108I (18.8%, n = 12/64), A98G (15.6%, n = 10/64), G190A (12.5%, n = 8), K101E/H (12.5%, n = 8), M41L (10.9%, n = 7/64), L74I/V (10.9%, n = 7/64), and H221Y (10.9%, n = 7/64) (Figure 1a,b). 2021 Genes Result HIV A98G;G190A;H221Y;K101E;K101H;K103N;L74I;L74V;M184V;M41L;T215F;T215Y;V108I;Y181C;Y181I;Y181V 242;267;367;289;289;132;337;337;106;313;188;188;216;158;158;158 246;272;372;296;296;137;343;343;111;317;195;195;221;167;167;167 RT 19 21 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. The most prevalent RT RAMs in pregnant women were as follows: K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), K219N/E/Q/R (5.9%, n = 2/34), and K238T (5.9%, n = 2/34) (Figure 1a,b). 2021 Genes Result HIV K103N;K219E;K219N;K219Q;K219R;K238T;M184V;P225H;Y181C;Y181I;Y181V 62;164;164;164;164;198;87;140;112;112;112 67;175;175;175;175;203;92;145;121;121;121 RT 19 21 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. We observed 4 PI-associated RAMs in 6 children/adolescents, as follows: the combination mutation I54V + V82A (n = 2), M46I/M (n = 1), and I84I/V (n = 1). 2021 Genes Result HIV I54V;I84I;I84V;M46I;M46M;V82A 97;138;138;118;118;104 101;144;144;124;124;108 PI 14 16 34576162 TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding. Next, we expressed wild-type Tat-EGFP, TatR52A-EGFP, TatR53A-EGFP, and TatR52AR53A-EGFP in HeLa lysate. 2021 International journal of molecular sciences Result HIV R53A 78 82 Tat;Tat;Tat 29;39;53 32;42;56 34576162 TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding. The mutations of the arginine residues, R52A and R53A, in the conserved basic region of Tat are crucial for specific TAR RNA binding and the enhanced refolding of the R52 mutant Tat. 2021 International journal of molecular sciences Result HIV R52A;R53A 40;49 44;53 Tat;Tat 88;178 91;181 34576162 TAR RNA Mediated Folding of a Single-Arginine-Mutant HIV-1 Tat Protein within HeLa Cells Experiencing Intracellular Crowding. The refolding enhancement factors for TatR52A-EGFP increased, as measured by the EGFP response, during a refolding period of 1 h in the absence and presence of TAR RNA at the optimized concentration (0.3 microM; Figure 3). 2021 International journal of molecular sciences Result HIV R52A 41 45 Tat 38 41 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Additionally, BAP Y712A-infected cells expressed 6-fold higher surface Env levels, as compared to BAP LL855AA-infected cells (Figure 4B). 2021 Viruses Result HIV Y712A 18 23 Env 71 74 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Analysis of surface Env expression showed an Env (b12)/p24 ratio of 0.2, 0.6 and 0.25 for BAP-V4 WT, Y712A and LL855AA, respectively (Figure 4A). 2021 Viruses Result HIV Y712A 101 106 p24;Env;Env 55;20;45 58;23;48 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. First, we used deconvolution microscopy to visualize the localization of Env and Gag in relation to VS using donor cells infected with either Env WT or Env Y712A-Gag-iCherryBAP-V4. 2021 Viruses Result HIV Y712A 156 161 Env;Env;Env;Gag;Gag 73;142;152;81;162 76;145;155;84;165 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. However, in the case of the Y712A mutant, the levels of Env transfer were 2.5- to 3.5-fold higher as compared to WT and LL855AA, respectively (Figure 4C,D, bottom rows). 2021 Viruses Result HIV Y712A 28 33 Env 56 59 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In calculating the ratio of Env/Gag transferred into target cells, we observed a significant 4-fold increase when using Y712A-infected cells, as compared to WT- or LL855AA-infected cells. 2021 Viruses Result HIV Y712A 120 125 Env;Gag 28;32 31;35 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In doing so, we observed a significant 7-fold increase in Env surface expression in Y712A-infected cells vs. 2021 Viruses Result HIV Y712A 84 89 Env 58 61 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In summary, the Y712A mutant resulted in less Gag and much more Env being transferred to target cells relative to the WT virus. 2021 Viruses Result HIV Y712A 16 21 Env;Gag 64;46 67;49 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In the 4 h cell-cell transfer experiments, we observed a significant reduction in the level of Gag p24 transfer into target cells when using donor cells infected with either the Y712A or LL855AA mutant viruses (Figure 4C,D, top rows). 2021 Viruses Result HIV Y712A 178 183 p24;Gag 99;95 102;98 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In the sorted CD4 target cells which had cell-associated Env or Gag puncta, we noted that cells cultured with Y712A Env-infected donor cells possessed significantly more Env-containing puncta, as compared to target cells cultured with WT Env-infected donors (Figure 5D). 2021 Viruses Result HIV Y712A 110 115 Env;Env;Env;Env;Gag 57;116;170;238;64 60;119;173;241;67 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In Y712A-infected cells, we observed a higher surface Env localization as opposed to the WT, with less Env within intracellular compartments (Figure 5A). 2021 Viruses Result HIV Y712A 3 8 Env;Env 54;103 57;106 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. J-BirA cells were infected with BAP-V4-WT, Y712A or LL855AA, and the levels of surface Env expression were quantified using the anti-Env Abs b12 or anti-biotin Abs and analyzed via flow cytometry (Figure 4A). 2021 Viruses Result HIV Y712A 43 48 Env;Env 87;133 90;136 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. J-BirA cells were nucleofected with BAP-V4-WT, -Y712A or -LL855AA expression vectors and used as infected donor cells in cell-cell transfer experiments with primary activated CD4 T cells as target cells. 2021 Viruses Result HIV Y712A 48 53 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Jurkat + BirA cells infected with the WT or Y712A HIV Gag-iCherry-BAP-V4 were co-cultured with primary activated CD4 T cells labeled with a Far Red vital dye. 2021 Viruses Result HIV Y712A 44 49 Gag 54 57 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Moreover, we observed significantly less Env and Gag co-localization within target cells cultured with Y712A Env- vs. 2021 Viruses Result HIV Y712A 103 108 Env;Env;Gag 41;109;49 44;112;52 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Next, we examined the localization of Gag and Env in VS target cells after HIV-1 cell-cell transfer conducted with the WT or Y712A mutant. 2021 Viruses Result HIV Y712A 125 130 Env;Gag 46;38 49;41 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Overall, this led to a 4-fold increase in the Env-to-Gag ratio detected in target cells co-cultured with HIV Y712A-infected donor cells, as compared to those co-cultured with WT HIV-infected cells (Figure 5G). 2021 Viruses Result HIV Y712A 109 114 Env;Gag 46;53 49;56 HIV infections 178 190 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. p24 staining fluorescence intensities, we observed a similar phenotype for BAP-V4, Y712A and LL855AA with 0.18, 0.5 and 0.26 Env (anti-biotin)/p24 ratios, respectively (Figure 4A). 2021 Viruses Result HIV Y712A 83 88 p24;p24;Env 0;143;125 3;146;128 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Surface-retained, non-recycled Y712A-Env can participate in VS formation and viral transfer, but the efficiency with which productive infection occurs in target cells under these conditions is reduced. 2021 Viruses Result HIV Y712A 31 36 Env 37 40 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. This indicates that BAP Y712A yielded the highest levels of surface Env accumulation as compared Env WT or Env LL855AA. 2021 Viruses Result HIV Y712A 24 29 Env;Env;Env 68;97;107 71;100;110 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. This was coupled with a 23% decrease in the Gag signal within Y712A vs. 2021 Viruses Result HIV Y712A 62 67 Gag 44 47 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Using WT-infected cells, the relative fluorescence Env/Gag ratio was 0.26 (Figure 4A), meaning the level of Env fluorescence was 25% that of Gag fluorescence; however, using Y712A-infected cells, the levels approached a 1-to-1 Env/Gag fluorescence ratio, indicating potentially four times the Env transferred (relative to Gag) across VSs as compared to WT Env (Figure 5D; bottom graph). 2021 Viruses Result HIV Y712A 174 179 Env;Env;Env;Env;Env;Gag;Gag;Gag;Gag 51;108;227;293;356;55;141;231;322 54;111;230;296;359;58;144;234;325 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. We examined if the Env Y712A and Env LL855AA mutations affected the accumulation of Env on the surface of infected cells. 2021 Viruses Result HIV Y712A 23 28 Env;Env;Env 19;33;84 22;36;87 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. We then calculated the Gag-to-Env ratios within VSs of Env WT- and Env Y712A-infected cells and found a significant decrease in the Gag-to-Env fluorescence ratio in Y712A-infected cell VSs, as compared to intracellular compartments (Figure 5B). 2021 Viruses Result HIV Y712A;Y712A 71;165 76;170 Env;Env;Env;Env;Gag;Gag 30;55;67;139;23;132 33;58;70;142;26;135 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. When examining the signal intensity of Env and Gag within co-localized puncta, we observed a 3-fold increase in the Env intensity in Y712A Env vs. 2021 Viruses Result HIV Y712A 133 138 Env;Env;Env;Gag 39;116;139;47 42;119;142;50 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. Most of the new mutations also encoded for resistance to prescribed drugs and these included L74I/V, T69D, V65R as NRTIs; A98G, V179E/F/D/F as NNRTs and I54V, F53L, L89T, G48A, K20T as PIs. 2021 The Pan African medical journal Result HIV A98G;F53L;G48A;I54V;K20T;L74I;L74V;L89T;T69D;V179D;V179E;V179F;V65R 122;159;171;153;177;93;93;165;101;128;128;128;107 126;163;175;157;181;99;99;169;105;139;139;139;111 NRTI;PI 115;185 120;188 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. K103N/S 56 (21.0%), G190S/A 39 (14.6%), Y181C/I 29 (10.9%), V108I 13 (4.9%), P225H 12 (4.5%), Y188L 7 (2.6%), M230L 7 (2.6%), L100I 5 (1.9%), V106 M 5 (1.9%), and K101P 2 (0.7%) were the mutations conferring resistance to NNRTIs. 2021 Medicine Result HIV G190A;G190S;K101P;K103S;L100I;M230L;P225H;V106M;V108I;Y181C;Y181I;Y188L;K103N 20;20;163;0;126;110;77;142;60;40;40;94;0 27;27;168;7;131;115;82;148;65;47;47;99;7 NNRTI 222 228 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. K65R/E/N and K70E mutations conferred resistance to TDF and M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E conferred resistance to AZT. 2021 Medicine Result HIV D67N;K219E;K219Q;K65E;K65N;K65R;K70E;K70R;L210W;M41L;T215F;T215Y 66;98;98;0;0;0;13;72;78;60;85;85 70;105;105;8;8;8;17;76;83;64;92;92 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. Lopinavir was the only PI class that demonstrated significant HIVDRM with mutations at V32I (2 patients), I47 V/A (2 patients), and V82A/F/T/S (3 patients). 2021 Medicine Result HIV I47V;V32I;V82A;V82F;V82S;V82T 106;87;132;132;132;132 113;91;142;142;142;142 PI 23 25 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. M184 V/I 87 (28.8%), K65R/E/N 27 (8.9%), L74 V 3 (1.0%), and Y115F 12 (4.0%) were the mutations conferring resistance to NRTIs, along with thymidine analog mutations (TAMs) M41L 14 (4.6%), D67N 17 (5.6%), K70R 20 (6.6%), L210W 10 (3.3%), T215Y/F 23 (7.6%), K219Q/E 32 (10.6%), and K65R/E/N 27 (8.9%). 2021 Medicine Result HIV D67N;K219E;K219Q;K65E;K65E;K65N;K65N;K65R;K65R;K70R;L210W;L74V;M184V;M41L;T215F;T215Y;Y115F 189;257;257;281;21;281;21;21;281;205;221;41;0;171;238;238;61 193;264;264;289;29;289;29;29;289;209;226;46;8;177;245;245;66 NRTI 121 126 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. M184 V/I confers resistance to 3TC and ABC in the presence of 2 or 3 TAMs. 2021 Medicine Result HIV M184V 0 8 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. M46I, which was found in 3 patients, confers Darunavir resistance. 2021 Medicine Result HIV M46I 0 4 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. There were no other mutations at L76 V, I47 V, I50 V, I54 M/L, or I84 V. 2021 Medicine Result HIV I47V;I50V;I54L;I54M;I84V;L76V 40;47;54;54;66;33 45;52;61;61;71;38 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. This study found no atazanavir resistance mutations (I50L, I84 V, or N88S). 2021 Medicine Result HIV I50L;I84V;N88S 53;59;69 57;64;73 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. At screening, one individual (Individual 153) exhibited a slightly high IC50 against TMR at screening (~96 nmol/l) and contained a key polymorphism of M426L. 2022 AIDS (London, England) Result HIV M426L 151 156 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Each clone contained either two key TMR changes at amino acid positions 375 and 426 (S375T or S375N along with M426L for Individuals 336 and 508, respectively) or a single M475I mutation [Individual 559; the emergent S375N mutation observed in the population sequence (Table 1) was not present in this clone] (Table 2). 2022 AIDS (London, England) Result HIV M426L;M475I;S375N;S375N;S375T 111;172;94;217;85 116;177;99;222;91 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Five individual envelope genes were synthesized, with one of the genes containing a baseline M426L polymorphism (MP11.38). 2022 AIDS (London, England) Result HIV M426L 93 98 Env 16 24 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. In terms of TMR and the population, Individual 474 possessed M426L at baseline and exhibited a slightly elevated IC50 (66 nmol/l) to TMR, with S375N emergent at PDVF along with M426L, resulting in a TMR IC50 of 372 nmol/l. 2022 AIDS (London, England) Result HIV M426L;M426L;S375N 61;177;143 66;182;148 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Individual 203 possessed M434T at baseline with a TMR IC50 of 9 nmol/l and had M426L and S375N emerge at PDVF alongside M434T (Table 4). 2022 AIDS (London, England) Result HIV M426L;M434T;M434T;S375N 79;25;120;89 84;30;125;94 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Table 4 summarizes that the clones obtained from the Screening and PDVF samples from both participants mirrored the population data in susceptibility, although S375N observed in both population sequences was not present in the clonal sequence. 2022 AIDS (London, England) Result HIV S375N 160 165 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. The other individual (Individual 153) contained the M426L polymorphism at screening and did not have any emergent mutations at the other three positions. 2022 AIDS (London, England) Result HIV M426L 52 57 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. The other participants either had no key polymorphisms, minor polymorphs (S375T) or mixtures (M426 M/T) but were susceptible to TMR at baseline (0.39--11 nmol/l). 2022 AIDS (London, England) Result HIV M426M;M426T;S375T 94;94;74 102;102;79 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. The outlier was the M426L-containing MP11.38 envelope, with an IC50 of nearly 413 nmol/l. 2022 AIDS (London, England) Result HIV M426L 20 25 Env 45 53 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Therefore, a sixth envelope was synthesized that was identical to MP11.38 except for an L426 M mutation (MP11.38(L426 M)). 2022 AIDS (London, England) Result HIV L426M 88 94 Env 19 27 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Using these clones, site-directed mutagenesis was performed to mutate the known TMR substitutions back to their consensus amino acid sequence (T/N375S, L426 M, and I475 M). 2022 AIDS (London, England) Result HIV I475M;L426M;N375S;T375S 164;152;143;143 170;158;150;150 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. At the 80 mg dose level, 2 participants were sequenced via UDS; in 1 participant, no NNRTI-resistance-associated mutations were found, whereas K103N (4.7%) and V189I (3.7%) were detected as minor variants in the other at the final timepoint. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV K103N;V189I 143;160 148;165 NNRTI 85 90 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. In another participant in the 600 mg panel exhibiting continued decline in HIV-1 RNA during the second week postdose, F227C was detected as a minority variant (21%) at 14 days postdose. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV F227C 118 123 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. In the participant with HIV-1 viral rebound, F227C comprised 99% of the viral population by 14 days postdose. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV F227C 45 50 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. Neither of these participants had F227C above the 2% threshold for reporting before dosing. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV F227C 34 39 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. Testing revealed the presence of F227C beginning at 10 days postdose in the 600 mg panel in the 1 participant exhibiting HIV-1 viral rebound; no other NNRTI-associated-resistance mutation was detected via chain-termination method sequencing. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV F227C 33 38 NNRTI 151 156 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. The E138G and V179D variants were detected in 1 participant each in the 600 mg panel before dosing, but were not detected postdose. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV E138G;V179D 4;14 9;19 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. At 17 days post-infection, the p24 level in Myr (+) AnkGAG1D4-S45Y-EGFP was 1000 times lower compared with the parental ankyrin. 2021 Biomolecules Result HIV S45Y 62 66 p24 31 34 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Both Myr (+) AnkGAG1D4 and Myr (+) AnkGAG1D4-S45Y expressed potency in inhibiting HIV-1 MIR virus. 2021 Biomolecules Result HIV S45Y 45 49 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Consistently with the p24 level, the level of HIV-1 p24 in SupT1/Myr (+) AnkGAG1D4-S45Y was significantly lower than in infected SupT1/Myr (+) AnkGAG1D4 at 21 days post-infection (Figure 9B). 2021 Biomolecules Result HIV S45Y 83 87 p24;p24 22;52 25;55 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Each lentivirus vector carries the gene encoding N-terminus myristoylated ankyrin protein with enhanced green fluorescence protein (EGFP) fusion, including Myr (+) AnkA32D3-EGFP, Myr (+) AnkGAG1D4-EGFP, and Myr (+) AnkGAG1D4-S45Y-EGFP. 2021 Biomolecules Result HIV S45Y 225 229 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Furthermore, the anti-HIV-1 activity of Myr (+) AnkGAG1D4-S45Y-EGFP in more extensive infection was investigated. 2021 Biomolecules Result HIV S45Y 58 62 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. HIV viral load assay confirmed the ability of Myr (+) AnkGAG1D4-EGFP and AnkGAG1D4-S45Y-EGFP to inhibit viral replication, as the HIV RNA copy number was lower than in the SupT1 cell control and irrelevant ankyrin (Figure 5C). 2021 Biomolecules Result HIV S45Y 83 87 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. HIV-1 RNA copies in SupT1/Myr (+) AnkGAG1D4 and SupT1/Myr (+) AnkGAG1D4-S45Y were verified as 2.06 x 105 and 2.61 x 105 copies/mL, respectively. 2021 Biomolecules Result HIV S45Y 72 76 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. However, at day 17, superior anti-HIV-1 activity of Myr (+) AnkGAG1D4-S45Y-EGFP was indicated (Figure 5B). 2021 Biomolecules Result HIV S45Y 70 74 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. However, HIV viral load assay indicated comparable anti-HIV-1 activity of Myr (+) AnkGAG1D4 and Myr (+) AnkGAG1D4-S45Y (Figure 9C). 2021 Biomolecules Result HIV S45Y 114 118 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. In addition, a single cycle assay was performed to investigate the role of AnkGAG1D4 and AnkGAG1D4-S45Y in inhibiting HIV-1 production. 2021 Biomolecules Result HIV S45Y 99 103 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. In addition, AnkGAG1D4 and AnkGAG1D4-S45Y did not drive mutation in the HIV-1 capsid. 2021 Biomolecules Result HIV S45Y 37 41 Capsid 78 84 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. In contrast to Myr (+) AnkGAG1D4-EGFP and SupT1/Myr (+) AnkGAG1D4-S45Y-EGFP, HIV p24 was detected at low levels. 2021 Biomolecules Result HIV S45Y 66 70 p24 81 84 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Interestingly, Myr (+) AnkGAG1D4-S45Y showed higher efficiency in protection, as syncytium cell formation was not observed until day 21 (Figure 8B), together with extended cell viability to day 21 (Figure 8C). 2021 Biomolecules Result HIV S45Y 33 37 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Moreover, HIV viral load confirmed that the number of RNA copies in SupT1/Myr (+) AnkGAG1D4 -S45Y-EGFP was 5.12 x 105 copies/mL, and in SupT1/Myr (+) AnkGAG1D4-EGFP was 7.20 x 106 copies/mL. 2021 Biomolecules Result HIV S45Y 93 97 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Myr (+) AnkGAG1D4-EGFP and Myr (+) AnkGAG1D4-S45Y-EGFP showed higher anti-HIV-1 potency based on 1000-fold lower HIV-1 production than the SupT1 cell control. 2021 Biomolecules Result HIV S45Y 45 49 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Myr (+) AnkGAG1D4-EGFP showed a delay in syncytium cell formation at 17 days post-infection, whereas Myr (+) AnkGAG1D4-S45Y-EGFP delayed the formation of syncytium cells to 21 days. 2021 Biomolecules Result HIV S45Y 119 123 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. On the other hand, SupT1/Myr (+) AnkGAG1D4-EGFP and SupT1/Myr (+) AnkGAG1D4-S45Y-EGFP had extended cell viability to 21 days with a greater percentage of viable cells in the latter. 2021 Biomolecules Result HIV S45Y 76 80 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Surprisingly, Myr (+) AnkGAG1D4-S45Y-EGFP retained the ability to inhibit HIV-1 replication. 2021 Biomolecules Result HIV S45Y 32 36 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Taken together, AnkGAG1D4-S45Y provides higher efficiency of intracellular antiviral effect on HIV-1 replication than the parental AnkGAG1D4. 2021 Biomolecules Result HIV S45Y 26 30 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. The concentration of HIV-1 p24 in culture supernatant of SupT1/Myr (+) AnkGAG1D4-EGFP and SupT1/Myr (+) AnkGAG1D4-S45Y-EGFP was 28.78 and 8.94 pg/mL, respectively. 2021 Biomolecules Result HIV S45Y 114 118 p24 27 30 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. The level of HIV-1 p24 in Myr (+) AnkGAG1D4-EGFP and Myr (+) AnkGAG1D4-S45Y-EGFP was 1.47 x 103 and 44.36 pg/mL, respectively. 2021 Biomolecules Result HIV S45Y 71 75 p24 19 22 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. The mean fluorescence intensity of CD4 in SupT1 cells and ankyrin-expressing SupT1 cells (Myr (+) AnkA32D3-EGFP, Myr (+) AnkGAG1D4-EGFP, and Myr (+) Ank GAG1D4-S45Y-EGFP) was 4.47 x 104, 5.58 x 104, 4.31 x 104, and 3.96 x 104, respectively (Figure 3B). 2021 Biomolecules Result HIV S45Y 160 164 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. The number of HIV RNA copies in SupT1/Myr (+) AnkGAG1D4-EGFP and SupT1/Myr (+) AnkGAG1D4-S45Y-EGFP was lower than in infected SupT1 cell controls and SupT1/Myr (+) AnkA32D3-EGFP (Figure 6C). 2021 Biomolecules Result HIV S45Y 89 93 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. The number of HIV RNA copies was verified as 8.11 x 105 copies/mL in SupT1/Myr (+) AnkGAG1D4-S45Y-EGFP and 1.02 x 107 copies/mL in SupT1/Myr (+) AnkGAG1D4-EGFP. 2021 Biomolecules Result HIV S45Y 93 97 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. The parental Myr (+) AnkGAG1D4 delayed the formation of syncytium cells in infected cells to 21 days post-infection, while no syncytium cells were observed in SupT1 cells expressing Myr (+) AnkGAG1D4-S45Y-EGFP. 2021 Biomolecules Result HIV S45Y 200 204 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. To investigate the antiviral activity of ankyrin targeting the HIV-1 capsid, SupT1 and SupT1 stable cells (SupT1/Myr (+) AnkA32D3-EGFP, SupT1/Myr (+) AnkGAG1D4-EGFP, and SupT1/Myr (+) AnkGAG1D4-S45Y-EGFP) were infected with HIV-1 NL4-3 laboratory strain virus at an MOI of 10. 2021 Biomolecules Result HIV S45Y 194 198 Capsid 69 75 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Viral load assay indicated that Myr (+) AnkGAG1D4-S45Y-EGFP performed better in blocking viral replication. 2021 Biomolecules Result HIV S45Y 50 54 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. A subcluster of sequences containing K160T in addition to G118R, E138K, and R263K showed the greatest evolutionary distance. 2022 Antimicrobial agents and chemotherapy Result HIV E138K;G118R;K160T;R263K 65;58;37;76 70;63;42;81 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. All CVW clonal and population sequences from participant 2 clustered together; all sequences contained G118R and were identical at the nucleotide level. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 103 108 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. At CVW, this participant lost the R263R/K integrase substitution, had no other INSTI or NRTI resistance-associated substitutions, and did not demonstrate genotypic or phenotypic dolutegravir resistance. 2022 Antimicrobial agents and chemotherapy Result HIV R263K;R263R 34;34 41;41 IN;INSTI;NRTI 42;79;88 51;84;92 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Baseline clones from participant 1 with R263K had reduced replication capacity compared with wild-type clones but demonstrated in vitro resistance only to elvitegravir, not dolutegravir or raltegravir. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 40 45 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Clonal and population sequences at CVW from participant 3 had multiple evolving pathways with >=2 integrase substitutions, with separate clusters forming for sequences containing H51Y and G118R (bootstrap = 96%) and those containing G118R, E138K, and R263K (bootstrap = 90%). 2022 Antimicrobial agents and chemotherapy Result HIV E138K;G118R;G118R;H51Y;R263K 240;188;233;179;251 245;193;238;183;256 IN 98 107 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Clones from participant 2 with G118R alone had increased INSTI resistance and decreased replication capacity compared with clones from participant 3 with G118R plus other integrase substitutions (Table 3). 2022 Antimicrobial agents and chemotherapy Result HIV G118R;G118R 31;154 36;159 IN;INSTI 171;57 180;62 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Dolutegravir dissociated from R263K integrase-DNA complexes faster than from wild-type integrase-DNA complexes, with a 1.8-fold increase in dissociation rate constant (koff) (Table 4). 2022 Antimicrobial agents and chemotherapy Result HIV R263K 30 35 IN;IN 36;87 45;96 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Five participants had G118R, which emerged in combination with other integrase substitutions in 3 participants or alone in 2 participants. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 22 27 IN 69 78 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Half of the dolutegravir bound to integrase-DNA complexes containing either R263K or G118R substitutions was retained at ~50 and ~10 h, respectively. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;R263K 85;76 90;81 IN 34 43 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. In addition, G118R forms a dual hydrogen bond with E92 and a hydrogen bond with the 3' hydroxy of the tDNA terminal thymine when bound with both vDNA and tDNA. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 13 18 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. In an effort to understand the emerging HIV-1 resistance mutants and their associated kinetics at a molecular level, we developed 2 HIV-1 integrase homology models containing either G118R or R263K based on the cryogenic electron microscopy (cryo-EM) intasome structure reported in the literature. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;R263K 182;191 187;196 IN 138 147 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. In the integrase R263K mutant homology model, all but one hydrogen bond with the substrate and catalytic loop were eliminated. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 17 22 IN 7 16 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Integrase mutants with G118R or G118R plus E138K exhibited faster dolutegravir dissociation than those with R263K, with 8.6- and 9.0-fold increases in koff values, respectively, relative to the wild type. 2022 Antimicrobial agents and chemotherapy Result HIV E138K;G118R;G118R;R263K 43;23;32;108 48;28;37;113 IN 0 9 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Median drug sensitivity and replication capacity were similar for clones from participant 3 with G118R plus H51Y versus clones with G118R plus E138K and R263K. 2022 Antimicrobial agents and chemotherapy Result HIV E138K;G118R;G118R;H51Y;R263K 143;97;132;108;153 148;102;137;112;158 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. One cluster contained all baseline sequences with R263 (bootstrap = 82%), and the other cluster contained only wild-type CVW sequences; all baseline clones containing R263K were identical at the nucleotide level. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 167 172 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. One participant (participant 1) had the integrase substitution R263R/K and NRTI resistance-associated substitutions K65R and M184I/V at baseline, despite no apparent prior INSTI treatment, but did not demonstrate in vitro dolutegravir phenotypic resistance. 2022 Antimicrobial agents and chemotherapy Result HIV K65R;M184I;M184V;R263K;R263R 116;125;125;63;63 120;132;132;70;70 IN;INSTI;NRTI 40;172;75 49;177;79 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The dissociation of raltegravir and elvitegravir from the G118R integrase-DNA complex was faster than that of the wild type, with 3.4- and 2.9-fold increases in koff, respectively, and demonstrated substantially shorter binding, with dissociative half-lives of 2.7 and 0.9 h, respectively. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 58 63 IN 64 73 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The homology model of the HIV-1 integrase G118R resistance mutant revealed that G118R partially occludes the integrase catalytic binding site, which would prevent dolutegravir and other INSTIs from binding effectively and cause dissociation from the HIV-1 intasome to be more rapid. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;G118R 42;80 47;85 IN;IN;INSTI 32;109;186 41;118;192 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The NRTI resistance-associated substitution M184V was detected at baseline in all 7 participants, 5 of whom retained this substitution at CVW and 2 of whom had no NRTI resistance-associated substitutions at CVW. 2022 Antimicrobial agents and chemotherapy Result HIV M184V 44 49 NRTI;NRTI 4;163 8;167 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The R263K substitution appeared to have little effect on dissociation of raltegravir (no change in koff) and elvitegravir (1.2-fold increase in koff) from integrase-DNA complexes relative to the wild type. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 4 9 IN 155 164 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The sixth participant had treatment-emergent Q148H and N155H in combination with other integrase substitutions. 2022 Antimicrobial agents and chemotherapy Result HIV N155H;Q148H 55;45 60;50 IN 87 96 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The treatment-emergent NRTI resistance-associated substitution D67N was observed in 1 participant. 2022 Antimicrobial agents and chemotherapy Result HIV D67N 63 67 NRTI 23 27 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Two of 3 participants with G118R plus other integrase substitutions also had treatment-emergent R263R/K. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;R263K;R263R 27;96;96 32;103;103 IN 44 53 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. When bound with both viral DNA (vDNA) and host target DNA (tDNA), G118R interacts with the 5' phosphate of the tDNA catalytic adenosine. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 66 71 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. A subcluster of sequences containing E138T, S147G, and R263K showed greater evolutionary distance (bootstrap = 96%). 2022 Antimicrobial agents and chemotherapy Result HIV E138T;R263K;S147G 37;55;44 42;60;49 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Additional integrase substitutions accumulated at weeks 136 and 168, with genotyping results of E138A/E/K/T, S147G/S, and R263K and E138T, S147G, and R263K, respectively. 2022 Antimicrobial agents and chemotherapy Result HIV E138A;E138E;E138K;E138T;E138T;R263K;R263K;S147G;S147G;S147S 96;96;96;96;132;122;150;109;139;109 107;107;107;107;137;127;155;116;144;116 IN 11 20 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Additionally, the L74M V75A G118R triple mutant HIV-1 integrase model shows a complex network of hydrogen bonds among R118, E92, and the tDNA terminus, as has been previously observed in G118R mutants. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;G118R;L74M;V75A 28;187;18;23 33;192;22;27 IN 54 63 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. All sequences from this cluster contained G118R and V151I; V151I was also present in all pretreatment sequences in this participant. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;V151I;V151I 42;52;59 47;57;64 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. All week 136 clonal sequences and 1 week 168 population sequence contained R263K and clustered together (bootstrap = 99%). 2022 Antimicrobial agents and chemotherapy Result HIV R263K 75 80 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Analysis for participant 2 showed that all week 192 clonal and population sequences collected after PDVF (week 168) clustered together (bootstrap = 85%); each sequence contained G118R, and 11 of 17 clones were identical at the nucleotide level. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 178 183 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Clones from participant 2 with G118R and either L74M or L74M/V75A treatment-emergent integrase substitutions exhibited increased fold changes in dolutegravir susceptibility and decreased integrase replication capacity compared with wild-type clones at baseline. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;L74M;L74M;V75A 31;48;56;61 36;52;60;65 IN;IN 85;187 94;196 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. For the 6 participants with emergent R263K or G118R, prior ART and optimized background regimen summaries and longitudinal reverse transcriptase and protease genotypic data may provide additional details on the emergence of resistance to dolutegravir. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;R263K 46;37 51;42 RT;PR 123;149 144;157 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Four of 5 participants with G118R had 1 additional treatment-emergent INSTI-associated substitution of L74M, E138E/K, E92E/Q, or T66I, respectively. 2022 Antimicrobial agents and chemotherapy Result HIV E138E;E138K;E92E;E92Q;G118R;L74M;T66I 109;109;118;118;28;103;129 116;116;124;124;33;107;133 INSTI 70 75 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Homology models of the HIV-1 integrase in the context of the intasome complex reveal that the L74M, V75A, and G118R resistance mutants are clustered near the HIV-1 integrase catalytic site. 2022 Antimicrobial agents and chemotherapy Result HIV G118R;L74M;V75A 110;94;100 115;98;104 IN;IN 29;164 38;173 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. However, week 136 clones from participant 1 with treatment-emergent R263K plus additional integrase substitutions resulted in increased fold change in dolutegravir susceptibility and decreased integrase replication capacity compared with clones at baseline and week 36. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 68 73 IN;IN 90;193 99;202 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. In 2 participants, a single INSTI-associated polymorphic substitution of E157Q or L74I (n = 1 each) was identified during the study, but given that no pretreatment samples from either participant were available for integrase assessment, it was not possible to determine if emergence had occurred during the study period. 2022 Antimicrobial agents and chemotherapy Result HIV E157Q;L74I 73;82 78;86 IN;INSTI 215;28 224;33 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. In the integrase R263K mutant, all but one hydrogen bond with the substrate and catalytic loop were eliminated, resulting in a differential geometry of the catalytic site relative to wild-type HIV-1 integrase. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 17 22 IN;IN 7;199 16;208 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Of 5 participants with available drug sensitivity data on or near PDVF, 4 (all of whom had G118R substitutions) demonstrated in vitro resistance to dolutegravir (Table 2). 2022 Antimicrobial agents and chemotherapy Result HIV G118R 91 96 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Of the 8 participants with resistance-associated integrase substitutions, 6 had treatment-emergent rare INSTI-associated substitutions G118R (n = 5) or R263K/R (n = 1) during the course of treatment (Table 2). 2022 Antimicrobial agents and chemotherapy Result HIV G118R;R263K;R263R 135;152;152 140;159;159 IN;INSTI 49;104 58;109 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. One of the 5 participants with detection of G118R (participant 6) was able to fully suppress (HIV-1 RNA level, <50 copies/mL) after confirmation of PDVF with the addition of lopinavir/ritonavir to the study regimen. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 44 49 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Sequences from participant 1 at pretreatment and week 36 clustered together, with none of the pretreatment and 4 of the 8 week 36 clones containing R263K. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 148 153 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Similar results were observed for clones from participant 3, who had only treatment-emergent G118R compared with clones analyzed at baseline. 2022 Antimicrobial agents and chemotherapy Result HIV G118R 93 98 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Testing at week 36 showed that virus from participant 1 had treatment-emergent R263K/R but was susceptible to dolutegravir (fold change, 1.1). 2022 Antimicrobial agents and chemotherapy Result HIV R263K;R263R 79;79 86;86 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Three participants had additional treatment-emergent resistance-associated reverse transcriptase substitutions of T215F/L, T215F/I/S/T and M230I/M, or M184V (n = 1 each) at PDVF. 2022 Antimicrobial agents and chemotherapy Result HIV M184V;M230I;M230M;T215F;T215F;T215I;T215L;T215S;T215T 151;139;139;123;114;123;114;123;123 156;146;146;134;121;134;121;134;134 RT 75 96 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Treatment-emergent R263K alone in clones at week 36 from participant 1 did not affect fold change in dolutegravir susceptibility or integrase replication capacity compared with wild-type clones at baseline. 2022 Antimicrobial agents and chemotherapy Result HIV R263K 19 24 IN 132 141 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. 2, D15E was predicted to destabilize binding of CCL3 and CCL13 and strengthen binding with CX3CL1, CCL2, and CCL4. 2021 Microbiology spectrum Result HIV D15E 3 7 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. A19D was also abundant and was present in ~63% (34/54) of samples. 2021 Microbiology spectrum Result HIV A19D 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. A19D was predicted to enhance binding of CCL5, CCL2, and CCL13. 2021 Microbiology spectrum Result HIV A19D 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Conversely, Y40N could substantially destabilize binding to the Australian gp120 with a smaller effect on binding to the Indonesian gp120 strain. 2021 Microbiology spectrum Result HIV Y40N 12 16 gp120;gp120 75;132 80;137 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. D15E and E18L were always carried together (haplotypes 11, 17, 18, and 19) as were T21A and F25L in haplotypes 5, 6, 9, and 13, but not 16. 2021 Microbiology spectrum Result HIV E18L;F25L;T21A;D15E 9;92;83;0 13;96;87;4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. D15E, E18L and T21A, F25L were also examined pairwise because the variant alleles were coinherited (see Table 2). 2021 Microbiology spectrum Result HIV E18L;F25L;T21A;D15E 6;21;15;0 10;25;19;4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. E18L was predicted to destabilize binding of CX3CL1 and CCL3. 2021 Microbiology spectrum Result HIV E18L 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Exceptions were the CCL4-G50C and CCL5-G50C complexes (Table S2). 2021 Microbiology spectrum Result HIV G50C;G50C 25;39 29;43 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. F25L and Y40N could destabilize gp120 binding, while E18L and N170D could enhance gp120 binding. 2021 Microbiology spectrum Result HIV E18L;N170D;Y40N;F25L 53;62;9;0 57;67;13;4 gp120;gp120 32;82 37;87 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. F25L was predicted to weakly destabilize binding of all chemokines except CCL13. 2021 Microbiology spectrum Result HIV F25L 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Furthermore, RTR carrying the R267K variant had higher FMD scores, marking superior cardiovascular health (P = 0.02). 2021 Microbiology spectrum Result HIV R267K 30 35 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Furthermore, the models predicted that F25L could destabilize binding of gp120 sequenced from an Indonesian patient while having less effect on binding of the Australian gp120 sequence. 2021 Microbiology spectrum Result HIV F25L 39 43 gp120;gp120 73;170 78;175 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. G50C (the only candidate distant from the chemokine-binding site of US28) was not predicted to destabilize binding of any chemokine except CCL4. 2021 Microbiology spectrum Result HIV G50C 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. In patients carrying the N170D variant, levels of IE-1-reactive antibodies and soluble type 1 interferon receptor (sIFN-alpha/betaR) were significantly greater after 12 months on ART. 2021 Microbiology spectrum Result HIV N170D 25 30 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Levels of HCMV DNA were not affected by R267K (data not shown), perhaps because they were strongly time dependent or because CMV replicates in tissue cells. 2021 Microbiology spectrum Result HIV R267K 40 45 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Mutations A19D, F25L, N170D, N171H, R267K, and V346A were present in all groups and all sample types. 2021 Microbiology spectrum Result HIV A19D;F25L;N170D;N171H;R267K;V346A 10;16;22;29;36;47 14;20;27;34;41;52 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. N170D may enhance binding of Australian gp120 and moderately enhance binding of Indonesian gp120 (Table 3). 2021 Microbiology spectrum Result HIV N170D 0 5 gp120;gp120 40;91 45;96 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. N170D was the most frequent and was present in ~90% (47/52) of samples. 2021 Microbiology spectrum Result HIV N170D 0 5 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Our models predicted that N170D would bind more strongly to CCL13 and more weakly to CCL2. 2021 Microbiology spectrum Result HIV N170D 26 31 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. R267K was predicted to have a minimal effect on binding of all chemokines. 2021 Microbiology spectrum Result HIV R267K 0 5 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. RTR carrying the R267K variant had higher levels of HCMV glycoprotein B (gB)-reactive antibodies (P = 0.02). 2021 Microbiology spectrum Result HIV R267K 17 22 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. T21A was predicted to destabilize binding of all chemokines to different degrees. 2021 Microbiology spectrum Result HIV T21A 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. The D15E, E18L double mutant favors binding to gp120 and CCL4 but not other chemokines, while T21A, F25L is more likely to inhibit binding to chemokines or gp120. 2021 Microbiology spectrum Result HIV D15E;E18L;F25L;T21A 4;10;100;94 8;14;104;98 gp120;gp120 47;156 52;161 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. This included G50C, which is closest to the interface with the G protein. 2021 Microbiology spectrum Result HIV G50C 14 18 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Variants R267K and N170D associated with antibody levels and are presented here. 2021 Microbiology spectrum Result HIV N170D;R267K 19;9 24;14 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Y40N was predicted to strongly destabilize binding of all chemokines, with a DeltaDeltaG of greater than 10 kcal/mol for CX3CL1, CCL3, and CCL4. 2021 Microbiology spectrum Result HIV Y40N 0 4 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. As for the NNRTI resistance, the majority of the HIV-1 strains showed high-level resistance to NVP (3.95%) and EFV (3.64%), and the main mutation was K103N/KN (data not shown). 2021 Frontiers in public health Result HIV K103K;K103N 150;150 158;157 NNRTI 11 16 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. Besides, 37.38% (40/107) of individuals carrying TDR were involved in the network, and K103N (42.5%, 17/40) was the most frequent TDR-associated mutation, followed by E138A (15%, 6/40), I54M (7.5%, 3/40), and Q58E (7.5%, 3/40). 2021 Frontiers in public health Result HIV E138A;I54M;K103N;Q58E 167;186;87;209 172;190;92;213 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. M184MI/V (0.38%) was the most prevalent NRTI-associated mutation, followed by T215F/L (0.30%). 2021 Frontiers in public health Result HIV M184I;M184M;M184V;T215F;T215L 0;0;0;78;78 8;8;8;85;85 NRTI 40 44 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. Most exhibited a potential low-level resistance to ETR (6.45%), EFV (5.84%), NVP (5.39%), and RPV (4.86%), and the main mutation was G190A. 2021 Frontiers in public health Result HIV G190A 133 138 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. Q58E/QE (0.91%) was the major prevalent PI-associated mutation, followed by I54M (0.23%). 2021 Frontiers in public health Result HIV I54M;Q58Q;Q58E 76;0;0 80;7;6 PI 40 42 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. The majority of HIV-1 strains with TDR mutations exhibited the degree of potential low-level resistance to NNRTI, ascribed to V179D/E/DE. 2021 Frontiers in public health Result HIV V179D;V179E 126;126 136;136 NNRTI 107 112 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. The most frequent NNRTI-associated mutation in our study was V179D/E/DE (4.93%), followed by K103N/KN (3.11%) and E138A/G (1.52%). 2021 Frontiers in public health Result HIV E138A;E138G;K103K;K103N;V179D;V179E 114;114;93;93;61;61 121;121;101;100;71;71 NNRTI 18 23 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. Twenty-nine individuals in the networks had potential low-level resistant mutations (V179D/DE/E). 2021 Frontiers in public health Result HIV V179D;V179E 85;85 95;95 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. A phenylalanine-to-tyrosine substitution (F440Y) at the fifth codon of the cleavage site was present in 43% (43/101) of the study sequences and was more common in subtype G than CRF02_AG, at 88% and 11%, respectively (P < 0.001, Table 2). 2022 The Journal of antimicrobial chemotherapy Result HIV F440Y 42 47 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. A substitution in the adjacent codon, K476Q, was noted in five sequences and accompanied F440Y in three of those. 2022 The Journal of antimicrobial chemotherapy Result HIV F440Y;K476Q 89;38 94;43 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. All K65R mutations in the study sequences were AGA. 2022 The Journal of antimicrobial chemotherapy Result HIV K65R 4 8 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. All participants with K65R also had M184I/V. 2022 The Journal of antimicrobial chemotherapy Result HIV K65R;M184I;M184V 22;36;36 26;43;43 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. At the preceding codon, K64, all but three samples had the trinucleotide AAG (K64K). 2022 The Journal of antimicrobial chemotherapy Result HIV K64K 78 82 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. However, its compensatory mutation T477A was present in 27% (27/101) of all sequences: 51% (22/43) of those with F440Y and 9% (5/58) of those without F440Y (P < 0.001). 2022 The Journal of antimicrobial chemotherapy Result HIV F440Y;F440Y;T477A 113;150;35 118;155;40 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. However, the codon usage for K65K was the same among the CRF02_AG and G sequences (92% AAA and 8% AAG). 2022 The Journal of antimicrobial chemotherapy Result HIV K65K 29 33 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. M184V was present in 87% of participants (88/101) at >=2% frequency, Y181C in 61% (62/101), K103N in 43% (41/101), M41L in 32% (32/101) and G190A in 31% (31/101). 2022 The Journal of antimicrobial chemotherapy Result HIV G190A;K103N;M41L;Y181C;M184V 140;92;115;69;0 145;97;119;74;5 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. No sequences contained the F440V mutation. 2022 The Journal of antimicrobial chemotherapy Result HIV F440V 27 32 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. One of the subtype G viruses had a K65N mutation (AAC), which causes intermediate resistance to tenofovir, abacavir, stavudine and didanosine. 2022 The Journal of antimicrobial chemotherapy Result HIV K65N 35 39 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. One-third of people with the CRF02_AG clade had K65R (33%; 18/54), compared with only 7% of people with subtype G (3/42; P = 0.002). 2022 The Journal of antimicrobial chemotherapy Result HIV K65R 48 52 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. Other changes in the p51-p66 cleavage site were G436K in one sequence, A437V in seven, A437T in one and E438D in three. 2022 The Journal of antimicrobial chemotherapy Result HIV A437T;A437V;E438D;G436K 87;71;104;48 92;76;109;53 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. Sixteen participants had all of the TAM 1 pathway mutations (M41L, L210W and T215Y), 11 had all of the TAM 2 pathway mutations (D67N, K70R, T215F and K219Q/E) and four had the mutations for both pathways. 2022 The Journal of antimicrobial chemotherapy Result HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 128;150;150;134;67;61;140;77 132;157;157;138;72;65;145;82 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. The exceptions to this were the subtype C sample and one subtype G, which both had the trinucleotide AAA (K64K), and one other subtype G sample, which had the trinucleotide AGG (K64R). 2022 The Journal of antimicrobial chemotherapy Result HIV K64K;K64R 106;178 110;182 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. The K65R mutation involves a switch between the basic amino acids lysine (K), which is coded for by AAA or AAG, and arginine (R), which is coded for by AGA, AGG, CGT, CGC, CGA or CGG (Figure 3). 2022 The Journal of antimicrobial chemotherapy Result HIV K65R 4 8 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. The K65R mutation was detected in the samples of 24% of participants (24/101), of whom 83% (20/24) had received tenofovir and 13% (3/24) had received stavudine, with two people having received both agents. 2022 The Journal of antimicrobial chemotherapy Result HIV K65R 4 8 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. The protease-p51 cleavage site (CTLNF/PISPI) contained mutations in nine (9%) sequences: two I851V, six P853H/S/T and two I854V. 2022 The Journal of antimicrobial chemotherapy Result HIV I851V;I854V;P853H;P853S;P853T 93;122;104;104;104 98;127;113;113;113 PR 4 12 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. There was also a high prevalence of mutations among the 12 participants who were sampled less than 1 year after initiating first-line treatment: 6 (50%) had TAMs present at >=2% frequency; 10 (83%) had core NRTI mutations (of which all 10 had M184IV and 7 also had other core NRTI mutations); and 12 (100%) had NNRTI mutations. 2022 The Journal of antimicrobial chemotherapy Result HIV M184I;M184V 243;243 249;249 NNRTI;NRTI;NRTI 311;207;276 316;211;280 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. There was only one participant who had more than one class of minority variant in the absence of any resistance mutations at >=20% frequency, and they had a core NRTI minority variant L74V at 8.6% and NNRTI minority variant E138A at 2.4%. 2022 The Journal of antimicrobial chemotherapy Result HIV E138A;L74V 224;184 229;188 NNRTI;NRTI 201;162 206;166 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. Three of the four CRF06_cpx samples also had the K65R mutation. 2022 The Journal of antimicrobial chemotherapy Result HIV K65R 49 53 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. 5.2% PLB; p = 1.00) in ASPIRE (Table 1) but E138A was detected more frequently in DVR seroconversions in the Ring Study. 2021 Journal of the International AIDS Society Result HIV E138A 44 49 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. All E138A-containing bulk-cloned viruses were tested for cross-resistance to commonly used NNRTIs for ART, including nevirapine, efavirenz, rilpivirine and etravirine. 2021 Journal of the International AIDS Society Result HIV E138A 4 9 NNRTI 91 97 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Amino acid changes, including G335D, N348I, T369I, A371V, and A376S associated with DPV or NNRTI resistance were not detected in the connection or RNAse H domains of HIV-1 RT. 2021 Journal of the International AIDS Society Result HIV A371V;A376S;G335D;N348I;T369I 51;62;30;37;44 56;67;35;42;49 NNRTI;RT 91;172 96;174 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Due to concerns that E138A could reduce the protective efficacy of DVR, we phenotyped clonal recombinant isolates from two samples from each arm (DPV-1, DPV-2, PLB-1 and PLB-2) to further investigate DPV susceptibility. 2021 Journal of the International AIDS Society Result HIV E138A 21 26 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. E138A was the most frequently detected mutation in HIV-positive ASPIRE participants. 2021 Journal of the International AIDS Society Result HIV E138A 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Major NNRTI mutations detected included K101E, K103N, K103S, V106M, V108I, E138A/G, V179D/I/T and H221Y, but the frequency of detection of each of these mutations did not differ by arm (Table 1). 2021 Journal of the International AIDS Society Result HIV E138A;E138G;H221Y;K101E;K103N;K103S;V106M;V108I;V179D;V179I;V179T 75;75;98;40;47;54;61;68;84;84;84 82;82;103;45;52;59;66;73;93;93;93 NNRTI 6 11 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Of these six, only one participant from the placebo arm had an NNRTI resistance mutation detected (K103N) in a sample collected 8 weeks after cessation of the placebo ring. 2021 Journal of the International AIDS Society Result HIV K103N 99 104 NNRTI 63 68 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. One sample had the L90M protease inhibitor resistance mutation with no other NRTI or NNRTI mutations. 2021 Journal of the International AIDS Society Result HIV L90M 19 23 PR;NNRTI;NRTI 24;85;77 32;90;81 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Only five samples were identified that had low-frequency NNRTI-associated polymorphisms or mutations not previously detected by Sanger sequencing, with the mutant frequency indicated in parentheses: K101R (1.4%), V108I (1.7%), E138A (9.3%), V179G (1.0%) and Y181C (1.2%). 2021 Journal of the International AIDS Society Result HIV E138A;K101R;V108I;V179G;Y181C 227;199;213;241;258 232;204;218;246;263 NNRTI 57 62 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Similarly, the HIV-1 V108I/E138A clone (DPV-2) had a greater reduction in DPV susceptibility (3.9-FC) than HIV-1 with V108I or E138A alone (0.8 and 2.6-FC). 2021 Journal of the International AIDS Society Result HIV E138A;E138A;V108I;V108I 27;127;118;21 32;132;123;26 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Single NNRTI mutations (with the exception of two PLB participants with E138A) did not reduce susceptibility to DPV (DPV-8, PLB 4-10), with FC ranging from 0.4 to 1.5. 2021 Journal of the International AIDS Society Result HIV E138A 72 77 NNRTI 7 12 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Systematic evaluation of the relative contribution of E138A and other NNRTI mutations to dapivirine susceptibility. 2021 Journal of the International AIDS Society Result HIV E138A 54 59 NNRTI 70 75 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The E138A/V179I clone (DPV-1) conferred the greatest reduction in DPV susceptibility (19-FC), followed by the E138A/V179T clone (11-FC). 2021 Journal of the International AIDS Society Result HIV E138A;E138A;V179I;V179T 4;110;10;116 9;115;15;121 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The K101E/E138A clone (PLB-1) conferred 12-FC reduction in DPV susceptibility, which is greater than either mutation alone (K101E, 3.6-FC; E138A, 4.2-FC). 2021 Journal of the International AIDS Society Result HIV E138A;E138A;K101E;K101E 10;139;4;124 15;144;9;129 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The RT polymorphism E138A occurs naturally in 5% of treatment-naive HIV-1-subtype C-positive individuals, but can also be selected by the DAPY class of NNRTIs. 2021 Journal of the International AIDS Society Result HIV E138A 20 25 NNRTI;RT 152;4 158;6 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The two PLB participants with E138A alone had 3.0 and 4.2-FC reduction in DPV susceptibility (p < 0.001). 2021 Journal of the International AIDS Society Result HIV E138A 30 35 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Two samples had nucleoside/tide reverse transcriptase inhibitor (NRTI) mutations; one with E44D and a second with A62A/V with the NNRTI mutation H221Y. 2021 Journal of the International AIDS Society Result HIV A62A;A62V;E44D;H221Y 114;114;91;145 120;120;95;150 RT;NNRTI;NRTI 32;130;65 53;135;69 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V179I or V179T alone was susceptible to DPV (1.0 and 1.4-FC), while E138A alone had 4.7-FC with respect to wild-type HIV-1. 2021 Journal of the International AIDS Society Result HIV E138A;V179T;V179I 68;9;0 73;14;5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. We also systematically reverted each NNRTI mutation to wild-type and phenotyped those clones to determine the relative effects of E138A alone and in combination with other NNRTI mutations compared to a bulk-cloned wild-type control. 2021 Journal of the International AIDS Society Result HIV E138A 130 135 NNRTI;NNRTI 37;172 42;177 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A P289P/S substitution was also observed in 1 breakthrough, although the effect of this change on GSK'254 susceptibility is not known. 2022 Antimicrobial agents and chemotherapy Result HIV P289P;P289S 2;2 9;9 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A364V is a substitution adjacent to the p25/p24 cleavage site (L363/A364), and in this assay. 2022 Antimicrobial agents and chemotherapy Result HIV A364V 0 5 p24 44 47 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A364V was the predominant substitution selected for in the parent V370A background. 2022 Antimicrobial agents and chemotherapy Result HIV V370A;A364V 66;0 71;5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Against GSK'254, T332S/V362I/PrR41G exhibited EC50 values of 13 nM (MPI, 88%) in the single-cycle assay and 7 nM (MPI, 97%) in the multiple-cycle assay. 2022 Antimicrobial agents and chemotherapy Result HIV T332S;V362I 17;23 22;28 PR 29 31 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. All 3 cultures selected for A364V by passage 1, and it was maintained in subsequent passages. 2022 Antimicrobial agents and chemotherapy Result HIV A364V 28 33 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Analysis of the Gag genotype in viruses that exhibited breakthrough generally found that GSK'254 treatment selected for virus containing the A364V or A364A/V change (5 of 9 samples with genotypic changes), with 2 instances each of the A366V and A366A/V substitutions observed. 2022 Antimicrobial agents and chemotherapy Result HIV A364A;A364V;A364V;A366A;A366V;A366V 150;141;150;245;235;245 157;146;157;252;240;252 Gag 16 19 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. H219Q/H was present in selections 1 and 2, and V218A was coselected with H219Q in selection 2. 2022 Antimicrobial agents and chemotherapy Result HIV H219H;H219Q;H219Q;V218A 0;73;0;47 7;78;7;52 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In addition to WT VLP, a VLP with V370 deleted (DeltaV370; a genotype characteristic of subtype C viruses) and one with the known resistance substitution A364V were analyzed. 2022 Antimicrobial agents and chemotherapy Result HIV A364V 154 159 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In all cases except for the VLP containing A364V, the GSK'254 surrogate dissociated more slowly than the GSK'795 surrogate from these HIV-1 Gag VLPs (mean GSK'254 surrogate half-life, 344 +- 91 min; mean GSK'795 surrogate half-life, 43 +- 7 min). 2022 Antimicrobial agents and chemotherapy Result HIV A364V 43 48 Gag 140 143 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In selection 1, T332P was maintained but acquired H219Q at passage 5 through passage 10. 2022 Antimicrobial agents and chemotherapy Result HIV H219Q;T332P 50;16 55;21 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Interestingly, T332S was observed in resistance selection by GSK'795, together with V362I. 2022 Antimicrobial agents and chemotherapy Result HIV T332S;V362I 15;84 20;89 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Notably, A366V is not present in the Los Alamos National Laboratory (LANL) HIV sequence database. 2022 Antimicrobial agents and chemotherapy Result HIV A366V 9 14 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Notably, the A364V-containing VLP was cleaved 9.2-fold faster than WT VLP, as previously reported. 2022 Antimicrobial agents and chemotherapy Result HIV A364V 13 18 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Notably, the H219Q substitution was also observed in selection experiments with GSK'795 and is a substitution likely involved in cyclophilin recruitment in vitro. 2022 Antimicrobial agents and chemotherapy Result HIV H219Q 13 18 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Notably, viruses expressing Gag polymorphisms at V370 have been shown to exhibit reduced susceptibility to bevirimat, while GSK'254 suppresses most SDMs with mutations located at V370 in single- and multiple-cycle assays except for those containing A366V/V370M. 2022 Antimicrobial agents and chemotherapy Result HIV A366V;V370M 249;255 254;260 Gag 28 31 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Overall, across 6 genotypes (excluding A364V), the GSK'254 surrogate dissociated 8.0-fold (the mean of GSK'254/GSK'795 relative dissociation from HIV-1 VLPs) more slowly than the GSK'795 surrogate. 2022 Antimicrobial agents and chemotherapy Result HIV A364V 39 44 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. S129I was also observed at passage 5 in selection 1 but was absent at passage 10. 2022 Antimicrobial agents and chemotherapy Result HIV S129I 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Selection 2 acquired A366V coselected with A224T and I378M, present at both passage 5 and passage 10. 2022 Antimicrobial agents and chemotherapy Result HIV A224T;A366V;I378M 43;21;53 48;26;58 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Selection 3 acquired A237A/T along with A364V. 2022 Antimicrobial agents and chemotherapy Result HIV A237A;A237T;A364V 21;21;40 28;28;45 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Selection 3 acquired A364V at passage 5, with an additional V203V/A change observed at passage 10. 2022 Antimicrobial agents and chemotherapy Result HIV A364V;V203A;V203V 21;60;60 26;67;67 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T332P was identified in selection 1 at passage 1. 2022 Antimicrobial agents and chemotherapy Result HIV T332P 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. The highly GSK'795-resistant R361K/V362I/L363M triple variant was previously observed in vivo but was inhibited by GSK'254 with EC50 values of 14 nM (MPI, 89%) in the single-cycle assay and 3 nM (MPI, 91%) in the multiple-cycle assay. 2022 Antimicrobial agents and chemotherapy Result HIV L363M;R361K;V362I 41;29;35 46;34;40 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. The T332S/V362I/PrR41G genotype was previously reported as selected in the presence of GSK'795 in a sequential-passage experiment and promoted high-level GSK'795 resistance. 2022 Antimicrobial agents and chemotherapy Result HIV T332S;V362I 4;10 9;15 PR 16 18 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. The VLPs containing the V362I or V370A polymorph were cleaved approximately 3-fold faster than the wild-type VLP, and VLPs containing V370A/DeltaT371 or DeltaV370 were cleaved 1.8- and 2.6-fold faster than WT VLP. 2022 Antimicrobial agents and chemotherapy Result HIV V362I;V370A;V370A 24;33;134 29;38;139 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. These 3 VLPs, along with 3 additional VLPs containing Gag polymorphisms (V370A/DeltaT371, V362I, and V370A), were examined for their innate rates of cleavage by HIV-1 protease in the absence of an MI. 2022 Antimicrobial agents and chemotherapy Result HIV V362I;V370A;V370A 90;73;101 95;78;106 PR;Gag 167;54 175;57 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Three different polymorphism-containing viruses were used: the wild type (WT), V370A-containing virus, and a DeltaV370-containing virus. 2022 Antimicrobial agents and chemotherapy Result HIV V370A 79 84 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Two NL4-3P373S viruses (WT and V370A-containing virus with no luciferase marker present) were used in serial-passage studies to select for virus with reduced susceptibility to GSK'254. 2022 Antimicrobial agents and chemotherapy Result HIV V370A 31 36 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Viruses containing A366V or A364V substitutions generally exhibited greatly reduced susceptibility to GSK'254. 2022 Antimicrobial agents and chemotherapy Result HIV A364V;A366V 28;19 33;24 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Viruses with V362I were approximately 4-fold more sensitive to GSK'254 than to GSK'795, whereas the one chimeric subtype B virus containing V362I/V370A was much more sensitive to GSK'254. 2022 Antimicrobial agents and chemotherapy Result HIV V362I;V362I;V370A 13;140;146 18;145;151 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Where data were available for both MIs, the GSK'254 surrogate was found to bind with 7.5-fold-greater affinity (the mean of GSK'254/GSK'795 relative binding affinity toward HIV-1 VLPs, excluding A364V), consistent with its improved antiviral activities toward the cognate viruses. 2022 Antimicrobial agents and chemotherapy Result HIV A364V 195 200 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). Besides DRMs assessed by PANDAA (K65R, M184V, K103N, Y181C and G190A), additional major DRMs to NRTI (L74I, D67N, K70E and K219R) were found in 3/120 participants (3%), as follows: L74I in combination with M184V were found in 2/120 participants (2%) and D67N +K70E+219R together with M184V occurred in 1 participant (1%). 2021 The Pan African medical journal Result HIV D67N;D67N;G190A;K103N;K219R;K65R;K70E;K70E;L74I;L74I;M184V;M184V;M184V;Y181C 108;254;63;46;123;33;114;260;102;181;39;206;284;53 112;258;68;51;128;37;118;264;106;185;44;211;289;58 NRTI 96 100 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). Pre-treatment drug resistance (K65R, M184V, K103N, Y181C and G190A) among the 120 participants was found in 14% (17/120). 2021 The Pan African medical journal Result HIV G190A;K103N;K65R;M184V;Y181C 61;44;31;37;51 66;49;35;42;56 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). Similarly, additional major DRMs to NNRTIs (V106M, K101E and P225H) were present in 5/120 participants (4%), as follows: V106M (2 participants) is a non-polymorphic mutation particularly common in subtype C viruses that causes high-level resistance to NVP and EFV and low/intermediate resistance to doravirine; K101E (found in 1 participant) is a non-polymorphic primarily accessory mutation that causes intermediate resistance to NVP and low-level resistance to EFV and finally P225H (found in 2 participants) is a non-polymorphic EFV-selected mutation. 2021 The Pan African medical journal Result HIV K101E;K101E;P225H;P225H;V106M;V106M 51;311;61;479;44;121 56;316;66;484;49;126 NNRTI 36 42 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). The mutation L74I is selected primarily by didanosine and abacavir (ABC) and occasionally by TDF; K219N/R are accessory thymidine analog mutations (TAMs) that usually occur in combination with multiple other TAMs; D67N is a non-polymorphic TAM associated with low-level resistance to zidovudine and stavudine and K70E cause low-level resistance to TDF and ABC. 2021 The Pan African medical journal Result HIV D67N;K219N;K219R;K70E;L74I 214;98;98;313;13 218;105;105;317;17 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Among NRTI resistance mutations, M184V (73.2%), and K219Q, (63.4%) were the most common resistance mutations detected from viraemic subjects, respectively. 2021 Infection and drug resistance Result HIV K219Q;M184V 52;33 57;38 NRTI 6 10 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Among the NNRTI associated mutations, Y188D was detected in all viraemic patients at low frequency (2-4%), which is not common in earlier reports. 2021 Infection and drug resistance Result HIV Y188D 38 43 NNRTI 10 15 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. In addition, multi-NRTI resistance mutation, Q151M was detected among 5 (12.2%) of the study subjects, which affects all NRTIs currently approved by the US FDA except tenofovir (Table 2). 2021 Infection and drug resistance Result HIV Q151M 45 50 NRTI;NRTI 19;121 23;126 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Of the 41 viraemic specimens genotyped, the major NNRTI resistance-associated mutations detected were: K103N (24.4%), P225H (7.3%), K101E (7.3%), V108I (7.3%), V90I (4.9%), V106M/A (9.8%), H221Y (4.9%), E138G/A (4.9%), and Y181C (4.9%). 2021 Infection and drug resistance Result HIV E138A;E138G;H221Y;K101E;K103N;P225H;V106A;V106M;V108I;V90I;Y181C 203;203;189;132;103;118;173;173;146;160;223 210;210;194;137;108;123;180;180;151;164;228 NNRTI 50 55 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Out of the 41 viraemic subjects 33 (80.5%) harbored NRTI resistance mutations, and 20 (48.8%) were found to have NNRTI resistance mutations, while 13 (31.7%) harbored other resistance mutations like V90A, K101Q and K103R. 2021 Infection and drug resistance Result HIV K101Q;K103R;V90A 205;215;199 210;220;203 NNRTI;NRTI 113;52 118;56 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. A remaining total of 529 sequences from 209 patients (Table S1) were subjected to the population analysis focusing on RH:N79S, IN:S17N and IN:M50I that exist in majority of these sequences. 2021 Viruses Result HIV M50I;N79S;S17N 142;121;130 146;125;134 IN;IN 127;139 129;141 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. After initial quality analysis, we excluded 27 sequences from four patients that contained integrase inhibitor (INI)-resistant mutations (Y143C/H/R; Q148H/K/R or N155H/S). 2021 Viruses Result HIV N155H;N155S;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 162;162;149;149;149;138;138;138 169;169;158;158;158;147;147;147 IN;IN 91;112 100;115 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. As described above, the virus replication assay indicated that an HIV containing the combination of M50I/V151I without RH:N79S or IN:S17N was a replication incompetent virus. 2021 Viruses Result HIV M50I;N79S;S17N;V151I 100;122;133;105 104;126;137;110 IN 130 132 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. As mentioned above, the constructs derived from mNL4.3 backbone contain the endogenous IN:V151I mutation. 2021 Viruses Result HIV V151I 90 95 IN 87 89 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. As shown in Figure 1A-C, RH:N79S, IN:S17N, and IN:M50I mutations were detected 52% (275 amplicons), 32% (169 amplicons), and 17% (90 amplicons), respectively. 2021 Viruses Result HIV M50I;N79S;S17N 50;28;37 54;32;41 IN;IN 34;47 36;49 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. As shown in Figure 3A, HIV(IN:M50I) and HIV(IN:V151I) single mutation replicated at rates comparable with HIV(WT) in primary CD4(+) T cells from day one after infection; however, a variant containing both mutations exhibited impaired replication. 2021 Viruses Result HIV M50I;V151I 30;47 34;52 IN;IN 27;44 29;46 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Based on the treatment histories, it appears that IN:M50I was detected in a treatment independent manner. 2021 Viruses Result HIV M50I 53 57 IN 50 52 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Evaluation of the Impact of IN:V151I Mutation on HIV Replication and Autoprocessing. 2021 Viruses Result HIV V151I 31 36 IN 28 30 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. HIV containing IN:M50I alone or IN:V151I alone demonstrated comparable amounts of p24 concentrations with that of HIV(WT) (110.0 +- 22.7 mug/mL, n = 4) (Table S4). 2021 Viruses Result HIV M50I;V151I 18;35 22;40 p24;IN;IN 82;15;32 85;17;34 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. However, those mutations were also present in mNL(IN:M50I). 2021 Viruses Result HIV M50I 53 57 IN 50 52 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. In striking contrast, the p24 concentrations of HIV(IN:M50I/V151I) stocks were 0.30 +- 0.1 mug/mL (n = 4) and thus around 0.3% of that in HIV(WT) (p < 0.01), indicating that the combination of mutation suppressed virus release. 2021 Viruses Result HIV M50I;V151I 55;60 59;65 p24;IN 26;52 29;54 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. In subtype B, nearly half of the sequences contained either RH:N79S or IN:S17N mutation, and surprisingly, 14 out of the 27 sequences did not contain the compensatory mutations (Figure 4A), and in subtype C, none of the three sequences possessed RH:N79S or IN:S17N mutations (Figure 4B). 2021 Viruses Result HIV N79S;N79S;S17N;S17N 63;249;74;260 67;253;78;264 IN;IN 71;257 73;259 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. In the clinical samples, RH:N20D, IN:M50I, IN:R127K, and IN:N232D were common mutations (Figure 2A,B). 2021 Viruses Result HIV M50I;N20D;N232D;R127K 37;28;60;46 41;32;65;51 IN;IN;IN 34;43;57 36;45;59 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Intriguingly, IN:V151I mutation appeared in the defect recombinant virus but not in clinical samples (Figure 2B). 2021 Viruses Result HIV V151I 17 22 IN 14 16 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. M50I/N79S, M50I vs. 2021 Viruses Result HIV M50I;N79S;M50I 11;5;0 15;9;4 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. M50I/S17N, M50I vs. 2021 Viruses Result HIV M50I;S17N;M50I 11;5;0 15;9;4 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Mature cleaved p17 and p24 fragments were detected in HIV(WT), HIV(M50I), and HIV(IN:V151), but not in HIV(IN:M50I/V151I), and accumulation of uncleaved GagPol polyprotein was detected in the mutant (Figure 3B) as we showed in previous work. 2021 Viruses Result HIV M50I;M50I;V151I 67;110;115 71;114;120 p24;IN;IN 23;82;107 26;84;109 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. N79S/S17N, M50I vs. 2021 Viruses Result HIV M50I;S17N;N79S 11;5;0 15;9;4 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. N79S/S17N, there are no significant differences in VL (Figure S1), indicating that VL is not correlated with M50I mutations. 2021 Viruses Result HIV M50I;S17N;N79S 109;5;0 113;9;4 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. non-M50I, M50I vs. 2021 Viruses Result HIV M50I;M50I 4;10 8;14 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. non-M50I/N79S, non-M50I/S17N, non-M50I vs. 2021 Viruses Result HIV M50I;M50I;M50I;N79S;S17N 4;19;34;9;24 8;23;38;13;28 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Our previous study using a series of recombinant HIV-1NL4.3 mutants demonstrated that virus containing IN:M50I mutation, mNL(IN:M50I), was a defective virus that suppressed the initial cleavage of GagPol polyproteins and viral release (note: the defective recombinant virus was depicted HIV(IN:M50I) in the previous work; however, to avoid confusion, the mutant is redesignated as mNL(IN:M50I) in the current study); RH:N79S and IN:S17N mutations rescued the defect. 2021 Viruses Result HIV M50I;M50I;M50I;M50I;N79S;S17N 106;128;294;388;420;432 110;132;298;392;424;436 IN;IN;IN;IN;IN 103;125;291;385;429 105;127;293;387;431 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Population Analysis of M50I in NIAID Clinical Samples. 2021 Viruses Result HIV M50I 23 27 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Population Analysis of the Combination of IN:M50I/IN:V151I in HIV Sequence Database. 2021 Viruses Result HIV M50I;V151I 45;53 49;58 IN;IN 42;50 44;52 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Since IN:M50I alone conferred a defective virus in GagPol processing with the suppression of virus release in our previous work, we presumed that the virus encoding only IN:M50I should contain uncharacterized compensatory mutation(s) other than the compensatory mutation (RH:N79S or IN:S17N), thus they may be released from cells with similar levels to other mutations (Table 1). 2021 Viruses Result HIV M50I;M50I;N79S;S17N 9;173;275;286 13;177;279;290 IN;IN;IN 6;170;283 8;172;285 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Since we were not able to produce a high TCID50 titer of virus stock of HIV(IN:M50I/V151I), we infected 10 x 106 cells of primary CD4(+) T cells with 10 ng of p24 amounts of virus for viral replication assay as described in the Materials and Methods. 2021 Viruses Result HIV M50I;V151I 79;84 83;89 p24;IN 159;76 162;78 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Surprisingly, 16% (14 amplicons) possessed IN:M50I alone without RH:N79S or IN:S17N compensatory mutation (Figure 1D). 2021 Viruses Result HIV M50I;N79S;S17N 46;68;79 50;72;83 IN;IN 43;76 45;78 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. The combination led to a replication-incompetent virus (0.01% of replication capability compared to HIV(WT), p < 0.001, n = 5), while HIV(IN:M50I) and HIV(IN:V151I) replicated 89 +- 6.5% (n = 5, p = 0.795) and 90 +- 3.8% (n = 5, p = 0.751) of HIV(WT) at day 7, respectively. 2021 Viruses Result HIV M50I;V151I 141;158 145;163 IN;IN 138;155 140;157 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. The defective virus sequence in our previous study, mNL(IN:M50I), was also included in the alignment (note: as described above, HIV(IN:M50I) in the previous work is renamed mNL(IN:M50I) in the current study). 2021 Viruses Result HIV M50I;M50I;M50I 59;135;180 63;139;184 IN;IN;IN 56;132;177 58;134;179 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. The mNL(IN:M50I) virus was constructed using a modified HIVNL4.3 strain (mNL). 2021 Viruses Result HIV M50I 11 15 IN 8 10 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. The resulted constructs, p(WT), p(IN:M50I alone), p(IN:V151I alone), and p(IN:M50I/V151I) were transfected into HEK293T cells, and then viral stocks were prepared as described in the Materials and Methods. 2021 Viruses Result HIV M50I;M50I;V151I;V151I 37;78;55;83 41;82;60;88 IN;IN;IN 34;52;75 36;54;77 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. The results demonstrated that among M50I alone vs. 2021 Viruses Result HIV M50I 36 40 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. These data indicated that the defective recombinant virus in the previous report of HIVmNL(IN:M50I) was caused by the combination of IN:M50I and IN:V151I mutations. 2021 Viruses Result HIV M50I;M50I;V151I 94;136;148 98;140;153 IN;IN;IN 91;133;145 93;135;147 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Thus, the combination of mutations resulted in a defective HIV, and since all 14 clinical isolates lacked IN:V151I mutation and were identified in plasma containing 1207-201,353 copies/mL (Table 1), this indicated that the virus is released from cells. 2021 Viruses Result HIV V151I 109 114 IN 106 108 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. To define whether a correlation between the VL range and M50I mutations is significant or not, we performed a statistical analysis using one way ANOVA unpaired method. 2021 Viruses Result HIV M50I 57 61 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. To delineate whether our hypothesis, that a combination of IN:M50I and IN:V151I causes a defective virus, was correct or not, we compared virus replication capability using a series of mutants. 2021 Viruses Result HIV M50I;V151I 62;74 66;79 IN;IN 59;71 61;73 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. To elucidate the population diversity of HIV carrying the IN:M50I/IN:V151I mutant in the plasma virus, we compared HIV sequences focusing on the mutations using NIAID and the Los Alamos National Laboratory (LANL) HIV database. 2021 Viruses Result HIV M50I;V151I 61;69 65;74 IN;IN 58;66 60;68 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We assessed for the mutation(s) that are commonly expressed in the 14 sequences but not in mNL(IN:M50I). 2021 Viruses Result HIV M50I 98 102 IN 95 97 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We need to study further to conclude the M50I effect on replication capability in clinical isolates. 2021 Viruses Result HIV M50I 41 45 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We next dissected the 90 amplicons containing IN:M50I, to define the population of combination; the combinations of RH:N79S/IN:M50I and IN:S17N/IN:M50I were detected in 40 (44%) and 13 (14%) amplicons, respectively, and RH:N79S/IN:S17N/IN:M50I was detected in 26% (23) amplicons (Figure 1D). 2021 Viruses Result HIV M50I;M50I;M50I;M50I;N79S;N79S 49;127;147;239;119;223 53;131;151;243;123;227 IN;IN;IN;IN;IN;IN 46;124;136;144;228;236 48;126;138;146;230;238 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We next endeavored to identify the unknown compensatory mutation in the 14 viruses containing M50I mutation alone. 2021 Viruses Result HIV M50I 94 98 34871089 Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. In addition, K65R plus Y115F (n = 1) and M184I (n = 2) were observed in combination with RPV RAMs. 2022 Antimicrobial agents and chemotherapy Result HIV K65R;M184I;Y115F 13;41;23 17;46;28 34871089 Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. The most frequent treatment-emergent NRTI RAM was M184V (4/15 patients [26.7%]). 2022 Antimicrobial agents and chemotherapy Result HIV M184V 50 55 NRTI 37 41 34871089 Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. The most frequent treatment-emergent RPV RAM at the last post-baseline time point was E138K (5/15 patients [33.3%]). 2022 Antimicrobial agents and chemotherapy Result HIV E138K 86 91 34871089 Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. Three patients had both treatment-emergent RPV RAM E138K and NRTI RAM M184V at the last post-baseline time point with genotypic data. 2022 Antimicrobial agents and chemotherapy Result HIV E138K;M184V 51;70 56;75 NRTI 61 65 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. Among those harbouring a M184 V/I mutation, no differences between reported PrEP intake (daily vs. 2022 AIDS (London, England) Result HIV M184I;M184V 25;25 33;33 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. All substitutions were present at baseline (n = 1, RNA, and n = 18, proviral DNA) except for participant #5, who had Y143C detected historically in plasma only. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV Y143C 117 122 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Notably, 4 had INSTI-R combined with NRTI-R substitutions relevant to the emtricitabine (FTC) or TAF components of the B/F/TAF regimen (M184V and/or K70E). 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV K70E;M184V 149;136 153;142 INSTI;NRTI 15;37 20;41 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Of the 8 amino acid positions listed with primary INSTI-R substitutions, 6 were detected in these participants: E92G (n = 3; 15%), Y143C/H (n = 6; 30%), S147G (n = 2; 10%), Q148H/K/R (n = 6; 30%), N155S (n = 1; 5%), and R263K (n = 2; 10%) (Table 2). 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV E92G;N155S;Q148H;Q148K;Q148R;R263K;S147G;Y143C;Y143H 112;197;173;173;173;220;153;131;131 116;202;182;182;182;225;158;138;138 INSTI 50 55 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Secondary INSTI-R substitutions included M50I (n = 4; 20%), L68V (n = 1; 5%), L74I/M (n = 1; 5%), S119P/R/T (n = 6; 30%), and G140S (n = 2; 10%). 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV G140S;L68V;L74I;L74M;M50I;S119P;S119R;S119T 126;60;78;78;41;98;98;98 131;64;84;84;45;107;107;107 INSTI 10 15 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. The treatment-naive participant had K103N and K70R in RT and Q148H and G140S in IN genes. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV G140S;K103N;K70R;Q148H 71;36;46;61 76;41;50;66 IN;RT 80;54 82;56 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. The treatment-naive participant with preexisting Q148H and G140S had a viral load of 30,000 copies/mL at baseline and was suppressed by week 4, maintaining viral loads of <50 copies/mL through week 48, and even week 216, without blips. 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV G140S;Q148H 59;49 64;54 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. This clinical isolate with Q148H+G140S was phenotypically susceptible to BIC (2.14-fold change, less than the cutoff of 2.5-fold), partially susceptible to DTG (4.45-fold change, greater than the cutoff of 4-fold), and resistant to EVG and RAL (PhenoSense Integrase assay, Monogram Biosciences). 2022 Journal of acquired immune deficiency syndromes (1999) Result HIV G140S;Q148H 33;27 38;32 IN 257 266 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. Given the low prevalence of non-B subtypes in the study population, associations between specific viral subtypes and the presence of polymorphic mutations were not particularly relevant in the context of the study population, e.g., V106I was present in all F1 subtypes; however, only 6/6661 F1 viruses were observed, while V106IM (generally combined with other NNRTI mutations) was observed in 231/6577 (3.5%) subtype B viruses. 2021 Pathogens (Basel, Switzerland) Result HIV V106I;V106I;V106M 323;232;323 329;237;329 NNRTI 361 366 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. However, other polymorphic non-SDRMs were also frequent (V106I (3.6%), V179DE (7.1%) in RT) (Figure 2b). 2021 Pathogens (Basel, Switzerland) Result HIV V106I;V179D;V179E 57;71;71 63;77;77 RT 88 90 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. Of note, no cases of bictegravir or dolutegravir resistance were observed among prior ARV-exposed participants (only 1 participant (0.7%) showed cabotegravir resistance due to the N155H mutation). 2021 Pathogens (Basel, Switzerland) Result HIV N155H 180 185 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. Other interesting clusters evidencing PDR transmission within the network included cluster PI-1, with 29 nodes, all men with PI resistance and median age 24 (22-28) enrolled across all years; cluster NRTI-1, with 23 nodes, 22 cisgender men and 1 cisgender woman, with median age 22 (10-27) and constant growth across all years; cluster complex-1, with 10 nodes, all men enrolled from 2018 to 2020 and median age 23 (20-30), 60% (6/10) with PI + NRTI + NNRTI resistance and 40% (4/10) with PI + NRTI resistance; and complex-2, with 7 nodes, all men with median age 26 (21-31) sharing PR M46I, L90M, RT M41L, D67N, T69D, L210W, T215D and RT K103N, Y181C (Figure 5). 2021 Pathogens (Basel, Switzerland) Result HIV D67N;K103N;L210W;L90M;M41L;M46I;T215D;T69D;Y181C 607;639;619;592;601;586;626;613;646 611;644;624;596;605;590;631;617;651 NNRTI;NRTI;NRTI;NRTI;PI;PI;PI;PI;PR;RT;RT 452;200;445;494;91;125;440;489;583;598;636 457;204;449;498;93;127;442;491;585;600;638 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. Resistance in IN was mainly due to R263K (1.6%) and E138AKT, G140ACS, Q148HKR (0.8% each) (Figure 6c). 2021 Pathogens (Basel, Switzerland) Result HIV E138A;E138K;E138T;G140A;G140C;G140S;Q148H;Q148K;Q148R;R263K 52;52;52;61;61;61;70;70;70;35 59;59;59;68;68;68;77;77;77;40 IN 14 16 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. Resistance to efavirenz/nevirapine was associated with transmission of K103NS alone in 7.9% (65/820) of clusters, K103NS plus other NNRTI mutations in 3.4% (28/820) clusters and with other NNRTI mutations in 8.0% (66/820) of clusters (Figure 5). 2021 Pathogens (Basel, Switzerland) Result HIV K103N;K103N;K103S;K103S 71;114;71;114 77;120;77;120 NNRTI;NNRTI 132;189 137;194 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. Some examples of the larger clusters evidencing NNRTI PDR transmission included cluster NNRTI-1, with 14 nodes, all men living in Mexico City with median age 28 years (IQR 23-31), all of them with K103NS; cluster NNRTI-2, with 27 nodes formed by men with median age 25 (23-30) enrolled across the complete study period, 11% (3/27) with K103NS and 74% (20/27) with other mutations; NNRTI-3, with 21 nodes, including men living in Mexico City and the State of Mexico and median age 24 (20-29), 62% (13/21) with K103NS; and cluster NNRTI-4, with 12 nodes, all men with median age 28 (25-32), all sharing E138A (Figure 5). 2021 Pathogens (Basel, Switzerland) Result HIV E138A;K103N;K103N;K103N;K103S;K103S;K103S 601;197;336;509;197;336;509 606;203;342;515;203;342;515 NNRTI;NNRTI;NNRTI;NNRTI;NNRTI 48;88;213;381;529 53;93;218;386;534 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. The largest clusters with INSTI PDR transmission were cluster INSTI-1, with 5 nodes sharing the S230R mutation, formed by 4 cisgender men and 1 transgender woman, with median age 23 (20-32); and cluster INSTI-2, with 4 nodes, all men sharing the E157Q and G163K mutations and median age 28 (26-34). 2021 Pathogens (Basel, Switzerland) Result HIV E157Q;G163K;S230R 246;256;96 251;261;101 INSTI;INSTI;INSTI 26;62;203 31;67;208 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. The most commonly observed DRMs were K103NS (24.1%) and M184VI (23.3%) in RT. 2021 Pathogens (Basel, Switzerland) Result HIV K103N;K103S;M184I;M184V 37;37;56;56 43;43;62;62 RT 74 76 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. The most frequent surveillance drug resistance mutations (SDRMs) were K103NS (6.7%) to NNRTI; M41L (1.2%) and T215CDEF (2.1%) to NRTI; M46IL (1.7%) to PI; and E138AKT (0.2%), Q148HKR (0.1%), and S230R (0.1%) to INSTI (Figure 2a). 2021 Pathogens (Basel, Switzerland) Result HIV E138A;E138K;E138T;K103N;K103S;M41L;M46I;M46L;Q148H;Q148K;Q148R;S230R;T215C;T215D;T215E;T215F 159;159;159;70;70;94;135;135;175;175;175;195;110;110;110;110 166;166;166;76;76;98;140;140;182;182;182;200;118;118;118;118 INSTI;NNRTI;NRTI;PI 211;87;129;151 216;92;133;153 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. The prevalence of K103NS varied from 5.2 to 7.7%, but this increase was not significant (p = 0.08) (Figure 4d). 2021 Pathogens (Basel, Switzerland) Result HIV K103N;K103S 18;18 24;24 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. The relatively high resistance to doravirine is noteworthy, and was mainly associated with mutations Y188L (4.5%, in most cases combined with V106I), L100IV (4.5%), K103EP (3.8%), P225H (3.0%). 2021 Pathogens (Basel, Switzerland) Result HIV K103E;K103P;L100I;L100V;P225H;V106I;Y188L 165;165;150;150;180;142;101 171;171;156;156;185;147;106 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. All 4 viruses demonstrated similar in vitro replication kinetics, suggesting that the L74I polymorphism does not impact virus growth. 2022 Antimicrobial agents and chemotherapy Result HIV L74I 86 90 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Breakthrough experiments were performed to assess the impact of L74I and HIV-1 subtype on the ability of cabotegravir to suppress in vitro viral replication. 2022 Antimicrobial agents and chemotherapy Result HIV L74I 64 68 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Cultures were infected with replication-competent NL4-3 viruses with L74, L74I, or chimeric NL4-3 viruses containing ConA6 HIV-1 subtype A6 I74 or I74L integrase sequences. 2022 Antimicrobial agents and chemotherapy Result HIV I74L;L74I 147;74 151;78 IN 152 161 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Emergence of resistance mutations in breakthrough viruses was rare, with only 1 replicate of NL4-3 L74I containing a Q148R mutation with 5 nM cabotegravir. 2022 Antimicrobial agents and chemotherapy Result HIV Q148R 117 122 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. However, when E138K was introduced into either clone, EC50 values against rilpivirine were above the biological cutoff, with fold change values of 2.38 and 2.21 for the viruses with PR/RT genes from NL4-3 and 92UG307, respectively. 2022 Antimicrobial agents and chemotherapy Result HIV E138K 14 19 PR;RT 182;185 184;187 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. However, when Q148R was introduced into either clone, EC50 values against cabotegravir were increased, with fold changes of 4.4 and 4.1 for NL4-3 and ConA6-containing viruses, respectively. 2022 Antimicrobial agents and chemotherapy Result HIV Q148R 14 19 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In addition to the L74I polymorphism, each participant who met CVF criteria had treatment-emergent INSTI resistance mutations of either G140R (n = 1) or Q148R (n = 2). 2022 Antimicrobial agents and chemotherapy Result HIV G140R;L74I;Q148R 136;19;153 141;23;158 INSTI 99 104 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Introduction of E138A or E138T into either clone resulted in fold change in EC50 values against rilpivirine of <=2.0, the biological cutoff for rilpivirine. 2022 Antimicrobial agents and chemotherapy Result HIV E138A;E138T 16;25 21;30 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Introduction of K101E also resulted in increased EC50 values against rilpivirine, with fold changes of 3.09 and 2.29 in the NL4-3 and 92UG307-PR/RT-containing viruses, respectively. 2022 Antimicrobial agents and chemotherapy Result HIV K101E 16 21 PR;RT 142;145 144;147 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. No Q148R mutations were observed when additional replicates were repeated in 3 independent experiments at 5 nM cabotegravir for >=100 days, indicating that the occurrence of Q148R in combination with L74I was rare at low concentrations and not observed at 410 nM, a concentration of cabotegravir below the mean minimum observed plasma concentration at steady-state in LA treatment studies (2.97 mug/ml). 2022 Antimicrobial agents and chemotherapy Result HIV L74I;Q148R;Q148R 200;3;174 204;8;179 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Replication-competent NL4-3 viruses with L74 or L74I and chimeric NL4-3 viruses containing ConA6 HIV-1 subtype A6 I74 or I74L integrase sequences were generated and used to infect MT-2 cells. 2022 Antimicrobial agents and chemotherapy Result HIV I74L;L74I 121;48 125;52 IN 126 135 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Sensitivity to cabotegravir (fold change in half-maximal effective concentration [EC50] values) was measured using replication-defective pseudoviruses to evaluate the impact of the L74I polymorphism in combination with integrase resistance mutations and HIV-1 subtype (Table 1). 2022 Antimicrobial agents and chemotherapy Result HIV L74I 181 185 IN 219 228 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Similar results were observed for NL4-3 viruses with L74 and ConA6-containing viruses with I74L plus either G140R or Q148R integrase mutations (data not shown); these results are consistent with a previous study demonstrating that Q148R alone was sufficient to produce a 5-fold shift in EC50 values. 2022 Antimicrobial agents and chemotherapy Result HIV G140R;I74L;Q148R;Q148R 108;91;117;231 113;95;122;236 IN 123 132 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Therefore, the known E138K and K101E mutations conferred EC50 fold change values consistent with in vitro resistance to rilpivirine equally across clones containing PR/RT genes from HIV-1 subtypes B and A1 (https://hivdb.stanford.edu/dr-summary/resistance-notes/NNRTI/). 2022 Antimicrobial agents and chemotherapy Result HIV E138K;K101E 21;31 26;36 NNRTI;PR;RT 262;165;168 267;167;170 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Therefore, the L74I integrase polymorphism alone or in combination with Q148R did not differentially impact in vitro sensitivity to cabotegravir across these HIV-1 subtype B and A6 integrase genes. 2022 Antimicrobial agents and chemotherapy Result HIV L74I;Q148R 15;72 19;77 IN;IN 20;181 29;190 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. These results suggest that L74I alone does not impact cabotegravir susceptibility in the context of NL4-3, an HIV-1 subtype B virus, or A6 integrase genes. 2022 Antimicrobial agents and chemotherapy Result HIV L74I 27 31 IN 139 148 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. This is consistent with the high prevalence of L74I in HIV-1 subtype A6 (http://www.hiv.lanl.gov/). 2022 Antimicrobial agents and chemotherapy Result HIV L74I 47 51 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Treatment with 5 nM cabotegravir resulted in viral breakthrough in 3 of 6 replicates for NL4-3 viruses, occurring between Days 28 and 42 for NL4-3 viruses with L74 and on Day 38 for NL4-3 viruses with L74I. 2022 Antimicrobial agents and chemotherapy Result HIV L74I 201 205 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Viral breakthrough occurred in 1 replicate each on Day 46 for chimeric ConA6 HIV-1 subtype A6 strains with either I74 or I74L. 2022 Antimicrobial agents and chemotherapy Result HIV I74L 121 125 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. When G140R was introduced into the NL4-3 variant containing L74I and the ConA6 integrase-containing virus with I74, no change was observed in cabotegravir susceptibility, each with fold changes of 0.9 (Table 1). 2022 Antimicrobial agents and chemotherapy Result HIV G140R;L74I 5;60 10;64 IN 79 88 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. Among the six study participants who met the virologic failure criteria (confirmed VL >50 copies/ml), two (33.3%) had RPV-associated mutations: K101E (n = 2) and Y181C (n = 1). 2022 Journal of the International AIDS Society Result HIV K101E;Y181C 144;162 149;167 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. Drug-resistance mutations detected among study participants with RPV-associated mutations included: participant #1 NNRTI mutations -- K101E, K103N, Y181C, G190A, N348I and NRTI mutation M184V; participant #2 NNRTI mutation K101E and NRTI mutation M184I. 2022 Journal of the International AIDS Society Result HIV G190A;K101E;K101E;K103N;M184I;M184V;N348I;Y181C 155;134;223;141;247;186;162;148 160;139;228;146;252;191;167;153 NNRTI;NNRTI;NRTI;NRTI 115;208;172;233 120;213;176;237 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. Two other study participants developed the V179D mutation, which is not associated with reduced susceptibility to RPV on its own. 2022 Journal of the International AIDS Society Result HIV V179D 43 48 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. A similar pattern could be observed upon infection with the V260I virus (Figure 2). 2021 International journal of molecular sciences Result HIV V260I 60 65 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Additionally, R263K was recently described to decrease HIV integration and to be associated with therapy failure using Dolutegravir in HIV-1 treated patients. 2021 International journal of molecular sciences Result HIV R263K 14 19 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. As expected from the HEXplorer prediction, the silent R263R mutation led to a similar splicing pattern as R263K, albeit, in contrast to the missense version R263K, a slight band for the most abundant mRNA species Tat2b was still present (Figure 3C). 2021 International journal of molecular sciences Result HIV R263K;R263K;R263R 106;157;54 111;162;59 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Compared with the parental sequence, the V260I mutation is predicted to have little effect on splice site recognition with a DeltaHZEI of -37.79, whereas R263K is predicted to result in a more severe change in splicing outcome with a DeltaHZEI of -132.16. 2021 International journal of molecular sciences Result HIV R263K;V260I 154;41 159;46 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. For R263K, a similar pattern was observed, as previously seen in the infection experiment (Figure 2) with SD2b recognition fully diminished. 2021 International journal of molecular sciences Result HIV R263K 4 9 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. For the missense mutation R263K with a DeltaHZEI of -132.16, a silent version R263R with a slightly lower DeltaHZEI of -107.8 was generated (Figure 3, lower panel). 2021 International journal of molecular sciences Result HIV R263K;R263R 26;78 31;83 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. For the missense mutation V260I with a DeltaHZEI of -37.79, a silent version V260V with a DeltaHZEI of -39.0 was generated. 2021 International journal of molecular sciences Result HIV V260I;V260V 26;77 31;82 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. In between the two splice donors, the missense mutations V260I and R263K and the silent mutations V260V and R263R, as well as the parental sequence, were inserted (Figure 3A). 2021 International journal of molecular sciences Result HIV R263K;R263R;V260I;V260V 67;108;57;98 72;113;62;103 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. In the C-terminal domain of the integrase coding region, i.e., the 3' end of HIV-1 pol, both mutations, V260I and R263K, are located within splicing regulatory elements:namely, ESS2b and ESE2b (Figure 1A). 2021 International journal of molecular sciences Result HIV R263K;V260I 114;104 119;109 IN;Pol 32;83 41;86 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. In the transfection experiment, the R263K mutant showed a reduced recognition of splice donor SD2b. 2021 International journal of molecular sciences Result HIV R263K 36 41 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. In the transfection experiments, the V260I variant showed a slight increase in the Tat2b message, which was in contrast to the HEXplorer prediction of a slight decrease in SD2b recognition. 2021 International journal of molecular sciences Result HIV V260I 37 42 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Interestingly, the silent version R263R with a similar but even slightly lower DeltaHZEI of -107.8 showed only a slight decrease in SD2b recognition, compared with the parental NL4-3 sequence (Figure 3B). 2021 International journal of molecular sciences Result HIV R263R 34 39 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Mutation R263K, however, largely alters the HEXplorer plot by an HZEI of -132.16, and thus, this mutation is predicted to increase SD2 use while the support of SD2b should be drastically decreased (Figure 1C). 2021 International journal of molecular sciences Result HIV R263K 9 14 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. There was no difference in SD2 and SD2b recognition upon insertion of the V260I or V260V silent mutation; however, a slight increase in SD2b recognition could be recognized, compared with the NL4-3 sequence, for both versions of the mutation. 2021 International journal of molecular sciences Result HIV V260I;V260V 74;83 79;88 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. This observation of the full loss of SD2b recognition upon the infection with the R263K virus was confirmed in three independent biological replicates. 2021 International journal of molecular sciences Result HIV R263K 82 87 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. This pattern was even more pronounced upon infection of PM1 cells with the R263K virus. 2021 International journal of molecular sciences Result HIV R263K 75 80 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. To further analyze the silent mutation R263R, the mutation was inserted into the pNL4-3 proviral plasmid by site-directed mutagenesis and used for infection. 2021 International journal of molecular sciences Result HIV R263R 39 44 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. V260I displays a change by an HZEI of -32.79, suggesting a potential only minor addition to the negative regulation of SD2b and a slightly increased enhancement of SD2. 2021 International journal of molecular sciences Result HIV V260I 0 5 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. A62V is a polymorphic mutation for sub-subtype A6 and was the most frequent NRTI DRM in Russia (174/465; 37.4%), Armenia (34/120; 28.3%), Azerbaijan (24/96; 25.0%), Belarus (21/158; 13.3%), and Uzbekistan (48/178; 27.0%). 2022 PloS one Result HIV A62V 0 4 NRTI 76 80 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. In Armenia, the most prevalent NNRTI DRM was V106I (7/120; 5.8%), which was also found in Russia (7/465; 1.5%), Azerbaijan (2/96; 2.1%), and Tajikistan (1/54; 1.9%). 2022 PloS one Result HIV V106I 45 50 NNRTI 31 36 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. In Tajikistan, the prevalence of A62V was found to be low (2/54; 3.7%). 2022 PloS one Result HIV A62V 33 37 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. In this case, we did not consider the A62V polymorphic mutation. 2022 PloS one Result HIV A62V 38 42 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. It should be noted that K103S, with a 0.6% prevalence, was found mainly in clustered sequences (2.6% vs 0.1%, p<0.001). 2022 PloS one Result HIV K103S 24 29 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. K103N was the most common DRM in Belarus (11/158; 7%) and Tajikistan (5/54; 9.3%), and was also observed in Russia (7/465; 1.5%), Azerbaijan (3/96; 3.1%), and Uzbekistan (3/178; 1.7%). 2022 PloS one Result HIV K103N 0 5 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. M41L in addition to A62V was found in Belarus (3/158; 1.9%) and Tajikistan (2/54; 3.7%). 2022 PloS one Result HIV A62V;M41L 20;0 24;4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. Mutations with a frequency higher than 1% in the study cohort, in clusters and outside clusters were E138A (5.3% vs 5.7%, overall, 5.6%, p = 0.830), K103N (3.5% vs 2.7%, overall 2.9%, p = 0.515), and V106I (3.5% vs 1.5%, overall 2.0%, p = 0.054), respectively. 2022 PloS one Result HIV E138A;K103N;V106I 101;149;200 106;154;205 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. T69D and L210W were also found in Armenia (3/120; 2.5%). 2022 PloS one Result HIV L210W;T69D 9;0 14;4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. The most frequent NNRTI DRM in Russia (32/465; 6.9%), Azerbaijan (7/96; 7.3%), and Uzbekistan (7/178; 3.9%) was E138A; this mutation was also found in Armenia (5/120; 4.2%) and Belarus (9/158; 5.7%); in Tajikistan, another substitution, i.e., E138G was found (1/54; 1.9%). 2022 PloS one Result HIV E138A;E138G 112;243 117;248 NNRTI 18 23 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. The most prevalent PI DRMs were M46I (3/120; 2.5%) and L10F (2/120; 1.7%) in Armenia and N88D (2/96; 2.1%) in Azerbaijan. 2022 PloS one Result HIV L10F;M46I;N88D 55;32;89 59;36;93 PI 19 21 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Additionally, we found that TDR to tipranavir/ritonavir (TPV/r) in CRF07_BC strain was extremely high [9.3%, (95% CI: 7.0-12.1%)], which was mainly related to the low-level resistance of TPV/r conferred by the high frequency of Q58E (Figure 3). 2021 Frontiers in microbiology Result HIV Q58E 228 232 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. All individuals in two of the CRF07_BC clusters carried Q58E (PI mutations, N = 29) and 52.6% (10/19) in the other CRF07_BC clusters carried K103N (NNRTI mutations). 2021 Frontiers in microbiology Result HIV K103N;Q58E 141;56 146;60 NNRTI;PI 148;62 153;64 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Eleven TDR strains harbored dual-class mutations (NRTI + NNRTI, n = 7; PI + NRTI, n = 3; and PI + NNRTI, n = 1), and all strains of CRF65_cpx (n = 7) carried a combination of the K103R and V179D mutations (Figure 2). 2021 Frontiers in microbiology Result HIV K103R;V179D 179;189 184;194 NNRTI;NNRTI;NRTI;NRTI;PI;PI 57;98;50;76;71;93 62;103;54;80;73;95 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. In the CRF01_AE network, there were five clusters with TDR mutations including two with M46L (PI mutations, n = 6) and one each with A98G (NNRTI mutations, n = 4), E138A (NNRTI mutations, n = 3), and K103R/V179D (NNRTI mutations, n = 3). 2021 Frontiers in microbiology Result HIV A98G;E138A;K103R;M46L;V179D 133;164;200;88;206 137;169;205;92;211 NNRTI;NNRTI;NNRTI;PI 139;171;213;94 144;176;218;96 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Of all clusters, 96.4% (53/55) of individuals with TDR mutation in these clusters were MSM and only two (in clusters with M46L and K103N) were infected through heterosexual transmission (HST) (Figure 4). 2021 Frontiers in microbiology Result HIV K103N;M46L 131;122 136;126 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Transmitted drug resistance mutations detected in more than 10 cases included PI [Q58E (n = 51) and M46ILV (n = 46)] and NNRTI [K103N (n = 26), E138AGKQ (n = 25), K103R/V179D (n = 20), and A98G (n = 12)] mutations. 2021 Frontiers in microbiology Result HIV A98G;E138A;E138G;E138K;E138Q;K103N;K103R;M46I;M46L;M46V;Q58E;V179D 189;144;144;144;144;128;163;100;100;100;82;169 193;152;152;152;152;133;168;106;106;106;86;174 NNRTI;PI 121;78 126;80 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. 4) shows that Gag mutation L449F and P453L significantly correlated to PI/r major resistance mutations. 2022 Scientific reports Result HIV L449F;P453L 27;37 32;42 Gag;PI 14;71 17;73 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Among the 18 Gag mutations significantly associated to PI/r exposure, ten mutations (P453L; E460A; R464G; V467E; I479K; Q474P; I479K; D480E; T487A; T487V) significantly differed between isolates from PI/r-treated vs RTI-treated (p < 0.05. 2022 Scientific reports Result HIV D480E;E460A;I479K;I479K;P453L;Q474P;R464G;T487A;T487V;V467E 134;92;113;127;85;120;99;141;148;106 139;97;118;132;90;125;104;146;153;111 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Class I included five mutations (L449F, D480N, L483Q, Y484P, T487V) that were completely absent or occurred with a frequency of < 1% in isolates from drug-naive patients and showed a significant increase in isolates from patients on PI/r-based regimen (5.59-11.18%). 2022 Scientific reports Result HIV D480N;L449F;L483Q;T487V;Y484P 40;33;47;61;54 45;38;52;66;59 PI 233 235 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Class II included four mutations (S462L, I479G, I479K, D480E) already present in isolates from drug naive patients at a frequency between 1 and 5% but with a significant increase in isolates from patients on PI/r-based regimen (5.59-37.76%). 2022 Scientific reports Result HIV D480E;I479G;I479K;S462L 55;41;48;34 60;46;53;39 PI 208 210 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Class III included nine mutations (P453L, E460A, R464G, S465F, V467E, Q474P, I479R, E482G, T487A) already present in isolates from drug naive patients at a frequency >= 5% but with a significant increase in isolates from PI/r-based patients (15.38-99.31%). 2022 Scientific reports Result HIV E460A;E482G;I479R;P453L;Q474P;R464G;S465F;T487A;V467E 42;84;77;35;70;49;56;91;63 47;89;82;40;75;54;61;96;68 PI 221 223 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Despite the slightly high median viremia in presence of two Gag mutations (L449F and Y484P) when compared to individuals with a wild-type residues, no significant variation was found in terms of viremia. 2022 Scientific reports Result HIV L449F;Y484P 75;85 81;90 Gag 60 63 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. for class 3, S465F was significantly more frequent in subtype categorized as other and E482G in CRF02_AG, p < 0.001. 2022 Scientific reports Result HIV E482G;S465F 87;13 92;18 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Four Gag P7(NC)-P6 mutations significantly associated to RTI exposure compared to naive patients were also significantly associated to PI/r exposure (L449F, p = 0.032; I479R, p = 0.002; E482G, p = 0.012; Y484P, p < 0.0001). 2022 Scientific reports Result HIV E482G;I479R;L449F;Y484P 186;168;150;204 191;173;155;209 RT;Gag;NC;Gag;PI 57;5;12;16;135 60;8;14;18;137 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In Class I Gag mutations, L449F showed a significant negative correlation (phi < 0 and p < 0.05) with M46I (phi = - 0.07, p = 0.019); in Class II, I479G correlated with I64M (phi = - 0.09, p = 0.011); in class III, E482G correlated with I54V (phi = - 0.19, p = 0.027), Q474P with M46I (phi = - 0.03, p = 0.044) and T487A with M46I (phi = - 0.21, p = 0.016) (Table 3). 2022 Scientific reports Result HIV E482G;I479G;I54V;I64M;L449F;M46I;M46I;M46I;Q474P;T487A 215;147;237;169;26;102;280;326;269;315 220;152;241;173;31;106;284;330;274;320 Gag 11 14 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In Class I, two mutations were positively correlated (phi > 0, p < 0.001) as pairs with protease major resistance mutations: L449F correlated with the major resistance mutations V32I (phi = 0.38, p = 0.008), I54V (phi = 0.27, p = 0.015) and L90M (phi = 0.32, p = 0.015); Y484P correlated with the major mutations I54V (phi = 0.33, p = 0.003) and V82A (phi = 0.26, p = 0.016). 2022 Scientific reports Result HIV I54V;I54V;L449F;L90M;V32I;V82A;Y484P 209;314;126;242;179;347;272 213;318;131;246;183;351;277 PR 89 97 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In Class II, D480E positively correlated with the major mutations I54V (phi = 0.31, p = p < 0.001) and V82A (phi = 0.26, p = 0.044). 2022 Scientific reports Result HIV D480E;I54V;V82A 13;66;104 18;70;108 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In Class III, only the Gag mutation P453L positively correlated with some major mutations as follows: L33F (phi = 0.28, p = 0.004), M46I (phi = 0.30, p = 0.001), I54L (phi = 0.27, p = 0.022), I54V (phi = 0.38, p < 0.001), V82A (phi = 0.20, p = 0.031), V82T (phi = 0.27, p = 0.021), and I84V (phi = 0.38, p < 0.001), (Table 3). 2022 Scientific reports Result HIV I54L;I54V;I84V;L33F;M46I;P453L;V82A;V82T 162;192;286;102;132;36;222;252 166;196;290;106;136;41;226;256 Gag 23 26 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In particular L449F correlated with L10F (phi = 0.25, p = 0.036); P453L with L10F (phi = 0.20, p = 0.046), Q58E (phi = 0.20, p = 0.046) and L89V (phi = 0.31, p = 0.002); Y484P with three PI/r accessory resistance mutations K20T (phi = 0.28, p = 0.024), and L89V (phi = 0.29, p = 0.011) (Table 3). 2022 Scientific reports Result HIV K20T;L10F;L10F;L449F;L89V;L89V;P453L;Q58E;Y484P 223;36;77;14;140;257;66;107;170 227;40;81;19;144;261;71;111;175 PI 187 189 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Indeed, in class 1, mutations L483Q, Y484P and T487V showed a significantly higher prevalence among subtype A1 infected individuals, when compared to other subtypes (p < 0.001, Table 2). 2022 Scientific reports Result HIV L483Q;T487V;Y484P 30;47;37 35;52;42 HIV infections 100 119 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Likewise, another cluster was formed by L449F and L90M (bootstrap value = 0.75, covariation frequency: 25.0%). 2022 Scientific reports Result HIV L449F;L90M 40;50 45;54 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Other Gag mutations P453L, E460A, S462L, R464G, S465F, V467E, Q474P, I479G, I479K, D480E, D480N, L483Q, T487A and T487V were only associated with PI/r exposure and not RTI when compared to ART naive patients. 2022 Scientific reports Result HIV D480E;D480N;E460A;I479G;I479K;L483Q;P453L;Q474P;R464G;S462L;S465F;T487A;T487V;V467E 83;90;27;69;76;97;20;62;41;34;48;104;114;55 88;95;32;74;81;102;25;67;46;39;53;109;119;60 RT;Gag;PI 168;6;146 171;9;148 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Regarding class 2, I479K was significantly more frequent in subtype categorized as other and D480E in subtype G, p < 0.001. 2022 Scientific reports Result HIV D480E;I479K 93;19 98;24 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Specifically, P453L clustered (bootstrap value = 0.33) with major PI/r resistance mutations M46I and I84V (covariation frequency: 40.9% and 31.8%, respectively). 2022 Scientific reports Result HIV I84V;M46I;P453L 101;92;14 105;96;19 PI 66 68 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. The most frequent mutations were M46I (21; 14.69%), I84V (11, 7.69%) and I54V (11, 7.69%). 2022 Scientific reports Result HIV I54V;I84V;M46I 73;52;33 77;56;37 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Another interesting finding was that the traditional Jalpha-Valpha connection was broken in T18A TCR/HLA-B*81:01/TL9 ternary structure. 2022 Frontiers in immunology Result HIV T18A 92 96 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. As shown in Supplementary Figure 3 , The bias location of T18A TCR towards HLA alpha2 helix was different with C12C TCR recognition. 2022 Frontiers in immunology Result HIV C12C;T18A 112;59 116;63 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Broken of the Traditional Jalpha Connection to Valpha in the T18A TCR. 2022 Frontiers in immunology Result HIV T18A 61 65 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Firstly, the backbone of TL9 peptide from two complexes (HLA-B*81:01-TL9 and HLA-B*81:01-TL9-T18A) were overlapped. 2022 Frontiers in immunology Result HIV T18A 93 97 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Functional analysis and biophysical methods were then used to explore whether escape mutations on the Gag TL9 epitope and HLA-B*81:01 presentation affect the affinity of T18A TCR. 2022 Frontiers in immunology Result HIV T18A 170 174 Gag 102 105 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. High-Affinity T18A TCR Bind to TL9 or TL9 Escape Variants Under HLA-B*81:01 Restriction. 2022 Frontiers in immunology Result HIV T18A 14 18 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. HIV Gag-TL9 epitope exhibits the same conformation during the binding of T18A TCR ( Figure 2A ). 2022 Frontiers in immunology Result HIV T18A 73 77 Gag 4 7 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. However, CDR3beta in T18A complex was functionally different from that of any other TCRs. 2022 Frontiers in immunology Result HIV T18A 21 25 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. In the docking of T18A TCR toward HLA-B*81:01, however, CDR3beta formed no contacts to the peptide and focused on the alpha2 helix of HLA ( Figure 3A ). 2022 Frontiers in immunology Result HIV T18A 18 22 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. In the interaction between T18A TCR and HIV-1 Gag-TL9 epitope presented by HLA-B*81:01, CDR2beta (amino acid sequence: FNNNVP) and CDR3alpha (amino acid sequence: VRGLNNAGNML) were the dominant contributors, which were characterized by strong hydrogen bond interactions involving multiple asparagine. 2022 Frontiers in immunology Result HIV T18A 27 31 Gag 46 49 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Interestingly, the CDR3alpha and CDR2beta of T18A sat above the peptide in the complex and dominated the interaction between TCR and peptide (CDR3alpha 52%, CDR2beta 39%) ( Figure 1D ). 2022 Frontiers in immunology Result HIV T18A 45 49 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. It suggested that the decreased capability of T18A TCR to the mutant epitopes may be mainly due to the decreased binding affinity of HLA molecule to TL9 variants. 2022 Frontiers in immunology Result HIV T18A 46 50 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Moreover, as CDR3beta of T18A swam away from the HIV peptide, CDR2beta replaced the normal role of CDR3beta, CDR3alpha and CDR2beta formed hydrogen bonds with the peptide ( Supplementary Figure 2B ). 2022 Frontiers in immunology Result HIV T18A 25 29 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Structural evidence showed that these two sites in the T18A TCR system were oriented toward the antigen-binding cleft regardless of the HLA restriction, and position 3 worked as a secondary anchored residue ( Figure 2B ). 2022 Frontiers in immunology Result HIV T18A 55 59 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. T18A adopt a docking angle of 43 across the antigen-binding groove in the complex, and few dramatic conformational changes of the TCR on the pHLA surface was found. 2022 Frontiers in immunology Result HIV T18A 0 4 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The binding capacity of T18A TCR to different p-HLA molecules were measured by in vitro surface plasmon resonance (SPR). 2022 Frontiers in immunology Result HIV T18A 24 28 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The complete analysis of the contacts between T18A TCR and TL9/HLA-B*81:01 complex is shown in the Supplementary Table 3 . 2022 Frontiers in immunology Result HIV T18A 46 50 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The Detailed Aspects of T18A TCR Recognition of HLA-B*81:01/TL9 Complex. 2022 Frontiers in immunology Result HIV T18A 24 28 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The general aspect of T18A TCR interaction with HLA-B*81:01/TL9 was shown in Figure 1A and the statistics of the crystal was described ( Supplementary Table 1 ). 2022 Frontiers in immunology Result HIV T18A 22 26 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The Overview of Crystal Structure of T18A TCR/HLA-B*81:01/TL9 Complexes. 2022 Frontiers in immunology Result HIV T18A 37 41 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The results showed that T18A could recognize the TL9 peptide presented by HLA-B*81:01 with a high affinity (Kd 4.7muM), and could recognize some escape variants of TL9, such as 3s-TL9 and 7s-TL9 ( Figure 5A ). 2022 Frontiers in immunology Result HIV T18A 24 28 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The T18A TCR accommodated peptide-HLA complexes in a similar traditional diagonal manner, with a total buried surface area (BSA) of 1732.6 A2 in HLA-B*81:01 background which fell within the range of known BSA. 2022 Frontiers in immunology Result HIV T18A 4 8 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Then, we compared T18A CDR3beta with those from other HIV recognition. 2022 Frontiers in immunology Result HIV T18A 18 22 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Thus, the unique role of the CDR3beta in the T18A TCR was not to contact the peptide but to form intensive interactions with the HLA alpha2 helix. 2022 Frontiers in immunology Result HIV T18A 45 49 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Unlike common "closed" Valpha cores, in T18A, the disruption of the beta strand made the core of Valpha domain more "open" ( Figure 4A ). 2022 Frontiers in immunology Result HIV T18A 40 44 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. We superimposed T18A (TRAV26-1/TRBV12-3) and 1E6 TCR (TRAV12-3/TRBV12-4) to compare the effect of "opened" or "closed" Jalpha-Valpha interactions on the entire TCR configuration. 2022 Frontiers in immunology Result HIV T18A 16 20 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Fifty-eight percent of the study population had both the K103E and K103R variants. 2022 Viruses Result HIV K103E;K103R 57;67 62;72 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. For example, E138K, a well-known escape mutation, was first identified in participant ML874 (A*68:02+) in the blood sample collected in 1996, and this DRM was also detected in the samples collected in 2003 from the same participant. 2022 Viruses Result HIV E138K 13 18 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. K103E frequently co-occurred with K103R, which had a prevalence of 61%. 2022 Viruses Result HIV K103R;K103E 34;0 39;5 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Moreover, E138A was identified first in participant ML264 (A*68:02+), and in samples collected in 1996, the DRM was also present in two samples collected from the same patient more than 7 and 7.5 years later in 2003. 2022 Viruses Result HIV E138A 10 15 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The drug with the highest levels of resistance was Lamivudine (3TC), with 41% of the participants having the M184I and/or K65ER mutations. 2022 Viruses Result HIV K65E;K65R;M184I 122;122;109 127;127;114 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The examination of the effect of the identified clinically important DRMs on the disease progression by Kaplan-Meier analysis showed that E138K_RT mutation is significantly associated with disease progression (p = 0.002) (Figure 2). 2022 Viruses Result HIV E138K 138 143 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The HLA-DRM associations involving HLA alleles at >10% frequency in Kenya are A*68:02 with DRMs G190ES (p = 0.008), IN E138K (p = 0.042), C*17:01 with DRMs M46I (p = 0.018), and IN E138K (p = 0.021). 2022 Viruses Result HIV E138K;E138K;G190E;G190S;M46I 119;181;96;96;156 124;186;102;102;160 IN;IN 116;178 118;180 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The most prevalent clinically important mutations for each drug class are as follows with the study sample prevalence: M184I (37%) (NRTI), E138AK (15%) (NNRTI), D30N (10%) (PI), and E138K (8%) (INSTI) (Figure 1). 2022 Viruses Result HIV D30N;E138A;E138K;E138K;M184I 161;139;139;182;119 165;145;145;187;124 INSTI;NNRTI;NRTI;PI 194;153;132;173 199;158;136;175 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The most prevalent single mutation overall, regardless of clinical importance, was K103E (RT), with a prevalence of 77% (result not shown). 2022 Viruses Result HIV K103E 83 88 RT 90 92 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The most significant association was between the mutation T97A and A*66:01 (p = 6.20-7; p = 0.001 after correction for multiple tests), a high-frequency allele in both Kenya and Uganda. 2022 Viruses Result HIV T97A 58 62 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The mutations conferring resistance to DTG, the newly introduced and WHO recommended INSTI, include E138K (IN), G118R, and R263K with prevalences of 6%, 3%, and 2%, respectively. 2022 Viruses Result HIV E138K;G118R;R263K 100;112;123 105;117;128 INSTI;IN 85;107 90;109 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. These results support the assumption that HLA class I-restricted CTLs exert selective immune pressure on RT138 amino acid and maintain K138AK mutations in these individuals over the course of infection. 2022 Viruses Result HIV K138A;K138K 135;135 141;141 RT 105 107 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Identification of a T146P mutation in the SIV-CL757 capsid. 2022 Microbiology spectrum Result HIV T146P 20 25 Capsid 52 58 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Prior studies have been successful in overcoming TRIM5alphaTFP/TFP restriction by the substitution of serines at positions 37 and 98 in the viral capsid; therefore, we chose to introduce these substitutions into CL757 to generate CL757-P37S/R98S (CL757-SS). 2022 Microbiology spectrum Result HIV P37S;R98S 236;241 240;245 Capsid 146 152 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. The viral peak and emergence at week 2 were restored with the correction of Thr-146 to Pro. 2022 Microbiology spectrum Result HIV T146P 76 90 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. 5A), while V32I, V32C, and A71V showed large delays in the initial cleavage of Gag. 2021 Virus evolution Result HIV A71V;V32C;V32I 27;17;11 31;21;15 Gag 79 82 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. 5C) is lower than WT for three variants (L10S, Q92I, and Q92N), suggesting that the rate of formation relative to disappearance is lower for these PR variants relative to WT. 2021 Virus evolution Result HIV L10S;Q92I;Q92N 41;47;57 45;51;61 PR 147 149 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. For example, L10S had the lowest fitness score, but processed Gag faster than any other mutant variant while A71V had the highest fitness score among the mutant variants but showed a large delay in Gag cleavage. 2021 Virus evolution Result HIV A71V;L10S 109;13 113;17 Gag;Gag 62;198 65;201 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. For example, we observed extremely low proficiency for V32I for any of the peptide substrates, while Q92I exhibited increased proficiency relative to WT PR for all three peptide substrates. 2021 Virus evolution Result HIV Q92I;V32I 101;55 105;59 PR 153 155 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Four variants (L10S, A71S, Q92N, and Q92I) exhibited small to modest changes in the disappearance of Gag. 2021 Virus evolution Result HIV A71S;L10S;Q92I;Q92N 21;15;37;27 25;19;41;31 Gag 101 104 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. In contrast, the peak quantity is dramatically higher for V32I and V32C. 2021 Virus evolution Result HIV V32C;V32I 67;58 71;62 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Of note, L10S has the second lowest activity for the TF-PR site in our analyses of peptide substrates, which should slow accumulation of mature protease and hinder the processing of all sites during viral maturation. 2021 Virus evolution Result HIV L10S 9 13 PR;PR 144;56 152;58 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Of note, the V32I mutation shows strong correlations with secondary mutations in patient isolates that may alleviate its functional defects. 2021 Virus evolution Result HIV V32I 13 17 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Of note, V32I and V32C also exhibited low proficiency for the MA-CA peptide. 2021 Virus evolution Result HIV V32C;V32I 18;9 22;13 Matrix;Capsid 62;65 64;67 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. The largest increase in proficiency we observed was about 2-fold for Q92I cutting PR-RT and for A71V cutting TF-PR. 2021 Virus evolution Result HIV A71V;Q92I 96;69 100;73 PR;PR;RT 82;112;85 84;114;87 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. The rate of cutting of MA-CA peptide by V32I is 30-fold reduced relative to WT. 2021 Virus evolution Result HIV V32I 40 44 Matrix;Capsid 23;26 25;28 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Two of the mutations in this set (V32I and A71V) have been shown to contribute to resistance to protease drugs, potentially providing opportunities to further understand the mechanisms of antiviral escape. 2021 Virus evolution Result HIV A71V;V32I 43;34 47;39 PR 96 104 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. We added the Q7K mutation to all variants in order to stabilize protease to self-cleavage as in previous studies. 2021 Virus evolution Result HIV Q7K 13 16 PR 64 72 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. We were not able to obtain enough purified protein of one variant (L10M) to perform enzyme activity measurements, and we dropped this variant from our panel. 2021 Virus evolution Result HIV L10M 67 71 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. A total of 12 polymorphic accessory mutations were detected, including E157Q (0.58%, 5/865), T97A (0.23%, 2/865), E138A (0.12%, 1/865), E157EQ (0.12%, 1/865), G163R (0.12%, 1 /865), Q95K (0.12%, 1/865), and S230R (0.12%, 1/865) (as shown in Figure 2). 2022 Pharmacogenomics and personalized medicine Result HIV E138A;E157E;E157Q;E157Q;G163R;Q95K;S230R;T97A 114;136;136;71;159;182;207;93 119;142;142;76;164;186;212;97 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. Additionally, the most common protease inhibitors associated mutation was Q58E (0.23%, 11/865), followed by M46I (4.05%, 5/865) and L33F (2.89%, 3/865)(as shown in Figure 2). 2022 Pharmacogenomics and personalized medicine Result HIV L33F;M46I;Q58E 132;108;74 136;112;78 PR 30 38 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. Among 12 IN-related polymorphic accessory mutations, only E138A, S230R and G163R mutations cause low-level resistance to INSTIs. 2022 Pharmacogenomics and personalized medicine Result HIV E138A;G163R;S230R 58;75;65 63;80;70 INSTI;IN 121;9 127;11 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. Furthermore, one patient having S230R mutation resulted in low-level resistance to RAL, EVG, DTG and BIC (as shown in Table 2). 2022 Pharmacogenomics and personalized medicine Result HIV S230R 32 37 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. M184V (0.23%, 2/865) was the most common nucleoside reverse transcriptase inhibitors (NRTIs) related mutation followed by T69D (0.12%, 1/865) and T69G (0.12%, 1/865). 2022 Pharmacogenomics and personalized medicine Result HIV T69D;T69G;M184V 122;146;0 126;150;5 NRTI;NRTI 41;86 73;91 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. NGS was more sensitive in detecting low-frequency mutations and a total of 4 mutations were detected by NGS but missed by Sanger sequencing which including M184V (1.31%), K65E (3.72%), E138G (1.21%), and Y188C (1.04%). 2022 Pharmacogenomics and personalized medicine Result HIV E138G;K65E;M184V;Y188C 185;171;156;204 190;175;161;209 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. The most common non-nucleoside reverse transcriptase inhibitors (NNRTIs) associated mutation was V179D (4.97%, 43/865), followed by V179E (4.05%, 35/865) and V106I (2.89%, 25/865). 2022 Pharmacogenomics and personalized medicine Result HIV V106I;V179D;V179E 158;97;132 163;102;137 NNRTI;NNRTI 16;65 52;71 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. Two patients have E138A and G163R mutations respectively and either of the two lead to low-level resistance to RAL and EVG. 2022 Pharmacogenomics and personalized medicine Result HIV E138A;G163R 18;28 23;33 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Analyzing the cumulative data from pooling all the sequence libraries, we found approximately 8% of total K258R proviruses were integrated into centromeres, a far higher frequency than for the WT virus (tenfold more, a difference at high statistical significance, with Fisher's exact t test, p < 0.0001). 2022 Nature communications Result HIV K258R 106 111 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Because HIV-1 integration is in part targeted through host factor interactions, it is plausible that the K258R mutation in the IN protein could modulate integration site selection by mediating differential binding of a specific host factor. 2022 Nature communications Result HIV K258R 105 110 IN 127 129 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Cumulative data of all libraries yields highly significant differences in integration pattern between the K258R and WT viruses (Table S1), but examining individual experiments shows a wide range in the magnitude of the effect. 2022 Nature communications Result HIV K258R 106 111 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. For all integrations by the K258R mutant IN that mapped to the centromere, we extracted the immediate flanking host genome sequences (10 bp upstream and 10 bp downstream), removed all identical junctions to be conservative and then aligned these to the alphoid repeat consensus sequence (AJ131208.1). 2022 Nature communications Result HIV K258R 28 33 IN 41 43 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. However, because it is known to bind to the core domain of HIV-1 IN (W131, I161, R166, Q168, Q170) we expect LEDGF binding would not be perturbed by the K258R mutation in the IN protein. 2022 Nature communications Result HIV K258R 153 158 IN;IN 65;175 67;177 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. However, we observed significant differences in the distribution of proviruses integrated at uniquely mapped sequences by the K258R mutant IN as compared to those formed by WT IN regardless of whether the NGS data was assessed in cumulative fashion (Table 1) or as the averages of three independent experiments. 2022 Nature communications Result HIV K258R 126 131 IN;IN 139;176 141;178 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. In agreement with the hot-spot analysis, we found a dramatic increase in integration frequency in centromeric regions specifically for proviruses integrated by the K258R mutant IN as compared to WT (Table 1). 2022 Nature communications Result HIV K258R 164 169 IN 177 179 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. In this assay we observed that viral DNA from the K258R mutant IN exhibited a 4-20-fold increase in CENP-C association on average relative to viral DNA from virus with WT IN. 2022 Nature communications Result HIV K258R 50 55 IN;IN 63;171 65;173 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. In this study, we focus specifically on the K258R point mutation in HIV-1 IN. 2022 Nature communications Result HIV K258R 44 49 IN 74 76 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. In three biological replicates, using independent infections, we again found higher frequencies of integrations near alpha repeats for the K258R mutant compared to the wild-type. 2022 Nature communications Result HIV K258R 139 144 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. It is of note that the quadruple acetylation mutant (K258/264/266/273R), though including the K258R mutation, did not produce the same dramatic phenotype as the K258R mutant, suggesting that the K258R mutation induces a distinctive gain-of-function phenotype not seen in the presence of the additional mutations. 2022 Nature communications Result HIV K258R;K258R;K258R 94;161;195 99;166;200 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Mutant K258R IN bound to the majority of previously reported host factors, but several binding partners were identified with enhanced binding to the K258R mutant IN. 2022 Nature communications Result HIV K258R;K258R 7;149 12;154 IN;IN 13;162 15;164 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Regardless of mapping algorithm, the data show that the K258R mutation in IN results in a dramatic redirection of integrations towards centromeres. 2022 Nature communications Result HIV K258R 56 61 IN 74 76 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Similarly, the WT IN showed the expected slight preference for integrating near CpG islands, but the K258R mutant IN showed less of this preferential targeting. 2022 Nature communications Result HIV K258R 101 106 IN;IN 18;114 20;116 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The alpha satellite bias was again only seen with the K258R mutant. 2022 Nature communications Result HIV K258R 54 59 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The analysis of the distribution of integrations of mutant K258R IN into unique mappable sites showed a loss of selective targeting to active genes as well as other features, but did not reveal a concomitant increase in integration frequency elsewhere. 2022 Nature communications Result HIV K258R 59 64 IN 65 67 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The assays, performed in independent infections, revealed a dramatic increase in the frequency of centromeric integration events for proviruses integrated by the K258R mutant IN confirming observations made by deep sequencing. 2022 Nature communications Result HIV K258R 162 167 IN 175 177 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The clustering we observe in the K258R mutant integration distribution could not be attributed to selective outgrowth of the infected cells in the population, as the samples were collected only 48 h post-infection. 2022 Nature communications Result HIV K258R 33 38 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The distribution of integration sites relative to transcription start sites, however, was unchanged by the K258R mutation. 2022 Nature communications Result HIV K258R 107 112 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R IN mutation causes a specific targeting of integrations into alphoid repeat sequences. 2022 Nature communications Result HIV K258R 4 9 IN 10 12 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R mutant IN increased integration frequency near centromeric alphoid repeats over the wild-type control by an average of 30-400 fold. 2022 Nature communications Result HIV K258R 4 9 IN 17 19 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R mutant virus was observed to integrate much more frequently than WT or any other acetylation IN mutant viruses at sites near the centromeres regardless of chromosome. 2022 Nature communications Result HIV K258R 4 9 IN 103 105 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R mutation in IN produces a broad range of centromeric integration frequencies whereas WT IN and other IN mutant viruses gave a tight, uniform distribution around the mean in all trials. 2022 Nature communications Result HIV K258R 4 9 IN;IN;IN 22;98;111 24;100;113 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R mutation of IN seems to uniquely redirect integrations to alpha satellite repetitive DNA and not other classes of repeat sequences. 2022 Nature communications Result HIV K258R 4 9 IN 22 24 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R mutation reduced this preference for integration into genes to below the level of random chance (matched random control, MRC). 2022 Nature communications Result HIV K258R 4 9 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R point mutation in IN caused only a very modest threefold defect in total reverse transcription (RT) as gauged by qPCR quantification of viral DNAs. 2022 Nature communications Result HIV K258R 4 9 RT;IN;RT 83;28;106 104;30;108 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The majority of these host factors were shared between WT and K258R mutant IN. 2022 Nature communications Result HIV K258R 62 67 IN 75 77 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The observed preference of K258R is specific for centromeric sequences, and we did not observe an increase in integration in the flanking peri-centromeric region. 2022 Nature communications Result HIV K258R 27 32 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The PCR data suggest that K258R virus is targeted to centromeres of many, if not all, chromosomes. 2022 Nature communications Result HIV K258R 26 31 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The potential for dramatically increased centromeric integration is a unique attribute of the K258R mutant IN. 2022 Nature communications Result HIV K258R 94 99 IN 107 109 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The redirection of integrations to the centromere caused by the K258R mutation in the IN protein is especially provocative in light of recent work linking centromeric HIV-1 integrations to viral latency and control. 2022 Nature communications Result HIV K258R 64 69 IN 86 88 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. These findings indicate that all viral DNA intermediates and viral mRNA levels are reduced by a comparable amount in the cells infected with virus carrying the K258R IN mutation, and that there is no significant defect at the specific step of integration. 2022 Nature communications Result HIV K258R 160 165 IN 166 168 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. These results indicate that the phenotype of the K258R mutant is not restricted to a single cell line but may be manifest in many cell types, including lymphoid T cells. 2022 Nature communications Result HIV K258R 49 54 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Thus, these binding data do not reveal a basis for the selectivity of the integration phenotype for K258R. 2022 Nature communications Result HIV K258R 100 105 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. To confirm that the K258R mutant IN is retargeting integrations to the centromere using a non-PCR based method, we made use of a fully orthogonal readout, utilizing simultaneous fluorescent in situ hybridization (FISH) of HIV-1 DNA and immunostaining of centromeres. 2022 Nature communications Result HIV K258R 20 25 IN 33 35 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. To determine whether the K258R mutant IN displayed any particular chromosomal preference, we also performed a qPCR assay utilizing chromosome-specific non-repetitive centromere primers to quantify specific centromeric DNA content present at the LTR-host genome junction. 2022 Nature communications Result HIV K258R 25 30 LTR;IN 245;38 248;40 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. To determine which class of repeats may be specifically targeted by the K258R mutant IN, sequencing reads were mapped directly to the RepeatMasker track from the UCSC Genome Browser. 2022 Nature communications Result HIV K258R 72 77 IN 85 87 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. To examine the distribution of integration sites more globally and determine where the K258R mutant IN is being redirected, we made use of scan statistics to identify regions of the genome with high numbers of viral integrations in an unbiased fashion, and specifically including highly repetitive sequences. 2022 Nature communications Result HIV K258R 87 92 IN 100 102 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. To our knowledge, the K258R mutant shows the most dramatic retargeting of integration sites induced by an IN mutation reported for any retrovirus so far. 2022 Nature communications Result HIV K258R 22 27 IN 106 108 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. To test this possibility, we generated mammalian expression vectors expressing either WT or K258R mutant IN protein and tested for host binding proteins. 2022 Nature communications Result HIV K258R 92 97 IN 105 107 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Treating the lysates with benzonase to remove nucleic acids did not have dramatic effects on the coIP of the proteins with IN, though there was a slightly increased loss of SMC4 and NCAPD3 from the K258R mutant IN. 2022 Nature communications Result HIV K258R 198 203 IN;IN 123;211 125;213 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Two factors involved in mitotic chromosome condensation (NCAPD3 and SMC4) along with multiple components of the catalytic core of the protein phosphatase I (PPI) complex were enriched in the MS screen of the factors bound with the K258R mutant IN as compared to WT. 2022 Nature communications Result HIV K258R 231 236 IN 244 246 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We did not observe a strong consensus sequence at the site of integration by WT IN, consistent with earlier reports, and the pattern was not substantially different at integration sites produced by the K258R mutant. 2022 Nature communications Result HIV K258R 202 207 IN 80 82 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We first confirmed the preference of the K258R mutant IN for integrating into centromeres using a Bowtie2-based sensitive local alignment strategy which allows for "soft-clipping" or omission of characters from the ends of reads in order to achieve the best alignment score. 2022 Nature communications Result HIV K258R 41 46 IN 54 56 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We further validated the centromeric integration preference of the K258R mutant IN using the BLAT mapping algorithm, which is more commonly used amongst published integration site analysis studies. 2022 Nature communications Result HIV K258R 67 72 IN 80 82 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We have found the K258R mutation present at very low frequency in proviral sequence repositories of latent proviruses, drug resistant mutants, and from patients on suppressive antiretroviral therapy but the extent of the enrichment of this mutation in these sequence pools is unclear due to the paucity of sequence information available. 2022 Nature communications Result HIV K258R 18 23 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We identified 43 and 56 proteins that bound to WT or K258R IN proteins, respectively, above the background of an empty vector control (Table S2). 2022 Nature communications Result HIV K258R 53 58 IN 59 61 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We identified an unprecedented number of hot-spot sites for integration by the K258R mutant IN that all clustered in centromeres (Table 2). 2022 Nature communications Result HIV K258R 79 84 IN 92 94 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We observe selective sites of insertion within the alpha satellite sequence by the K258R mutant IN protein, with two preferred spots of integration at nucleotide position 6 and 69 in the alphoid consensus sequence. 2022 Nature communications Result HIV K258R 83 88 IN 96 98 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. We observed no notable differences in the frequency of proviral integration sites occurring in proximity to any of four pre-infection chromatin modifications (H3K27ac, H3K36me3, H3K4me3 and H3K9me3) generated by the K258R mutant IN as compared to WT. 2022 Nature communications Result HIV K258R 216 221 IN 229 231 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. While all mutants exhibited a slight increase in preferential targeting to the centromeres, the K258R mutation alone strongly retargeted integration into centromeres at a strikingly high frequency, indicating that the effect of the K258R mutation in IN is unique to this residue, and not a general feature of blocking IN acetylation. 2022 Nature communications Result HIV K258R;K258R 96;232 101;237 IN;IN 250;318 252;320 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. While the initial integration site mapping indicated that the K258R IN mutation induces a preference for integrating into centromeric regions, these algorithms do not identify specific target sequences and in fact do not even consider integration into the vast majority of repetitive sequences, which are largely excluded from the hg38 human reference genome. 2022 Nature communications Result HIV K258R 62 67 IN 68 70 35336931 DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks). Baseline resistance mutations (K103N, V106I + E138A, and V108I, respectively) were detected in three patients (3.4%). 2022 Viruses Result HIV E138A;K103N;V106I;V108I 46;31;38;57 51;36;43;62 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. 4e), that may explain the compensatory role of the K588R mutation. 2022 Retrovirology Result HIV K588R 51 56 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. A mapping of potential Env-EL9 structural changes showed a close proximity between L592R and K588R mutations, both located in the same alpha-helix. 2022 Retrovirology Result HIV K588R;L592R 93;83 98;88 Env 23 26 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. After October 2014, all sequences in B2 displayed the combination of K588R + L592R mutations. 2022 Retrovirology Result HIV K588R;L592R 69;77 74;82 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Compared to the WT virus, the L592R mutation caused an unstable folding to the overall protein stability. 2022 Retrovirology Result HIV L592R 30 35 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Furthermore, we examined the changes over time, observing the replacement of the Env-EL9 mutant L592R by the double mutant K588R + L592R. 2022 Retrovirology Result HIV K588R;L592R;L592R 123;96;131 128;101;136 Env 81 84 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. However, the incorporation of the K588R mutation provided higher protein stability. 2022 Retrovirology Result HIV K588R 34 39 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. In order to identify structural changes associated with the L592R and K588 + L592R mutations in Gp41, we evaluated Gp160 protein folding stability by discrete optimized protein energy (DOPE) of the Env-EL9 WT and mutants. 2022 Retrovirology Result HIV L592R;L592R 60;77 65;82 gp160;gp41;Env 115;96;198 120;100;201 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. In plasma viral RNA sequences, K558R was a minority (2 out 5 sequences) in May 2012, preceding LVC. 2022 Retrovirology Result HIV K558R 31 36 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. In proviral DNA, the WT Env-EL9 sequence was detected in A variant while the L592R mutant appeared in 1 out the 2 sequences obtained for the B1 variant (March 04) and in all sequences for the B2 from March 04 to December 15. 2022 Retrovirology Result HIV L592R 77 82 Env 24 27 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Interestingly, L592R variant showed lower infectivity than WT. 2022 Retrovirology Result HIV L592R 15 20 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Moreover, the addition of K588R mutation to the L592R mutant resulted in a sixfold (+- 1.4) increase compared to the WT in infectivity assays. 2022 Retrovirology Result HIV K588R;L592R 26;48 31;53 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Next, to further investigate the impact of Env-EL9 mutations in CD8 + T-cell immune escape, we synthetized Gag-DA9 and Env-EL9 wild-type (WT) peptides and Env-EL9 peptides containing K558R and L592R variants alone or combined. 2022 Retrovirology Result HIV K558R;L592R 183;193 188;198 Env;Env;Env;Gag 43;119;155;107 46;122;158;110 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Taken together, these results indicate the compensatory role in infectivity of the K588R mutation. 2022 Retrovirology Result HIV K588R 83 88 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. The second mutation in Env-EL9 (K588R) was detected earlier in plasma samples (May 12) than proviral DNA (October 14). 2022 Retrovirology Result HIV K588R 32 37 Env 23 26 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. These results suggest a relationship between the diminished infectivity of the L592R mutant and sustained viral control and the compensatory role of K588R in infectivity and protein stability. 2022 Retrovirology Result HIV K588R;L592R 149;79 154;84 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. These results support a stronger immune pressure of HLA-B*14:02 restricted CD8 + T-cells towards the Env-EL9 epitope than to the Gag-DA9 epitope and the selection of CD8 + T-cell HIV-1 escape variants at positions K558R and L592R of the Env-EL9 epitope driven by immune pressure. 2022 Retrovirology Result HIV K558R;L592R 214;224 219;229 Env;Env;Gag 101;237;129 104;240;132 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. We detected a reduction of Env-EL9 WT responses over time and a lack of responsiveness towards the L592R variant. 2022 Retrovirology Result HIV L592R 99 104 Env 27 30 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. We identified two mutations in Env-EL9 from Lys to Arg at position five K588R and Leu to Arg at position nine (L592R). 2022 Retrovirology Result HIV K588R;L592R 72;111 77;116 Env 31 34 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Among the 12 patients, three harbored the M228I variant. 2022 BMC immunology Result HIV M228I 42 47 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. IFN-gamma ELISPOT assays were performed for patients 320019 (381 days post-infection (dpi)) and 325020 (309 dpi) whose viral isolates represented the wild-type GI11 (Gag) epitope and the M228I variant (Table 2). 2022 BMC immunology Result HIV M228I 187 192 Gag 166 169 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Indeed, the emergence of the D490G variant did not affect the CD4 T-cell count or VL in patient 321145. 2022 BMC immunology Result HIV D490G 29 34 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Patient 320088 had similar responses to wild-type VV9 (Gag) and the V143T variant, but showed diminished responses to the A138T, V143A, and M142W/V143T variants. 2022 BMC immunology Result HIV A138T;M142W;V143A;V143T;V143T 122;140;129;68;146 127;145;134;73;151 Gag 55 58 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Patient 325029 showed a strong response to wild-type VV9 (Gag), slightly diminished responses to the A138T and M142W/V143T variants, and weak responses to the V143T and V143A variants. 2022 BMC immunology Result HIV A138T;M142W;V143A;V143T;V143T 101;111;169;117;159 106;116;174;122;164 Gag 58 61 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Several variants of the RL9 (Gag) and HL9 (Gag) epitopes were detected in our cohort, such as R436K, L437I, and A431V within RL9 (Gag) and S146P, S146L, S146A, and L147V within HL9 (Gag) (Table 2). 2022 BMC immunology Result HIV A431V;L147V;L437I;R436K;S146A;S146L;S146P 112;164;101;94;153;146;139 117;169;106;99;158;151;144 Gag;Gag;Gag;Gag 29;43;130;182 32;46;133;185 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Some variants (R106G/K, Q107K/R/G, E108D, D111G, L112S, and W113R) in the RV9 (Nef) epitope developed in 6/7 patients during follow-up. 2022 BMC immunology Result HIV D111G;E108D;L112S;Q107G;Q107K;Q107R;R106G;R106K;W113R 42;35;49;24;24;24;15;15;60 47;40;54;33;33;33;22;22;65 Nef 79 82 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Specifically, the founder viruses from three patients (320018, 440230 and 321145) carried the M142W/V143T and V143T variants; the V143T variant in patient 320853 and the M142W/V143T variants in patient 325020 were newly developed during follow-up; and the V143A variant in patient 320019 and variants M142W/V143T and V143T in patient 325020 appeared transiently and had disappeared at the next follow-up time point. 2022 BMC immunology Result HIV M142W;M142W;M142W;V143A;V143T;V143T;V143T;V143T;V143T;V143T 94;170;301;256;130;100;110;176;307;317 99;175;306;261;135;105;115;181;312;322 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. The GI9 (Pol) epitope was conserved in our cohort, and only one patient (321145) harbored the D490G variant during follow-up, with a variant rate of 61.85% at 38 days of HIV-1 infection, increasing to 100% at 3 months of HIV-1 infection (Table 2). 2022 BMC immunology Result HIV D490G 94 99 Pol 9 12 HIV infections 170 185 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. The I113K, I118V, I118S, I118P, and E121K variations were observed in seven patients (Table 2). 2022 BMC immunology Result HIV E121K;I113K;I118P;I118S;I118V 36;4;25;18;11 41;9;30;23;16 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. The impact of the E121K variant on RI10 (Pol) was assessed in patient 325029 (337 dpi), in whom the predominant viral isolates harbored E121K. 2022 BMC immunology Result HIV E121K;E121K 18;136 23;141 Pol 41 44 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. The M228I variant rates in patients 320135, 325020, and 320019 were 75.68%, 29.71%, and 3.10%, respectively, at seroconversion, decreasing to 38.53%, 8.71%, and 0% at the next follow-up time point. 2022 BMC immunology Result HIV M228I 4 9 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. The results showed that these two patients had a diminished IFN-gamma response to the D490G variant of GI9 (Pol), indicating that the D490G variant represented an escape mutation. 2022 BMC immunology Result HIV D490G;D490G 86;134 91;139 Pol 108 111 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. VV9 (Gag)-specific T-cell responses may have promoted the selection of the V143T, V143A, V143T, and M142W/V143T variants in 7 of the 12 patients (Table 2). 2022 BMC immunology Result HIV M142W;V143A;V143T;V143T;V143T 100;82;75;89;106 105;87;80;94;111 Gag 5 8 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. We synthesized the epitope containing the D490G variant and performed an IFN-gamma ELISPOT assay on PBMCs from patients 320019 (381 dpi) and 325029 (337 dpi). 2022 BMC immunology Result HIV D490G 42 47 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. Bricault reported that D474N and R476K mutations were associated with resistance to neutralization of VRC01, and shifts of D474N and R476K were also observed in our experiment. 2022 Frontiers in cellular and infection microbiology Result HIV D474N;D474N;R476K;R476K 23;123;33;133 28;128;38;138 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. Residue 461 is ranked 6th among the 10 highest in terms of co-variation with CD4bs bNAb VRC01 and structure, and variation of the S461N mutation was observed in our study. 2022 Frontiers in cellular and infection microbiology Result HIV S461N 130 135 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. Residue W277 increased to 83.33% in 2020 after the mutation was observed initially in 2018, suggesting that the F277W mutation may also be related to 10E8 neutralization resistance. 2022 Frontiers in cellular and infection microbiology Result HIV F277W 112 117 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. The F277W mutation was observed, but the F277I mutation associated with resistance to neutralization of 10E8 was not observed. 2022 Frontiers in cellular and infection microbiology Result HIV F277I;F277W 41;4 46;9 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. The S465T mutation increased from 20% in 2016 to 100% in 2020, suggesting that S465T may be associated with VRC01 resistance. 2022 Frontiers in cellular and infection microbiology Result HIV S465T;S465T 4;79 9;84 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. A decrease in the Asp25-Ile50 distance up to the non-mutated system levels at most of the simulation period indicates an inward (towards core of the active site) curling of the flap in the M46I mutation systems. 2022 Viruses Result HIV M46I 189 193 Asp 18 21 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. A significant decrease in van der Waals contribution in the SQ-MI complex indicates an important role of the M46I mutation in decreasing the interaction between saquinavir and HIV 1 protease binding. 2022 Viruses Result HIV M46I 109 113 PR 182 190 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. An increased SASA value in the M46I HIV-1 protease structure in comparison to the wild-type protease might be due to the conformational flexibility in the protein. 2022 Viruses Result HIV M46I 31 35 PR;PR 42;92 50;100 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Based on these facts, our results indicate that WT and SQ-WT showed closed-flap conformation (<1.72 nm), and the M46I mutation stabilized the semi-open conformation (~1.72 nm), whereas the saquinavir-bound mutated structure depicted the open conformation (>1.72 nm Asp25-Ile50 distance) during the simulation period. 2022 Viruses Result HIV M46I 113 117 Asp 265 268 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Changes in the SASA value indicated that M46I decreased the hydrophobic compactness of the protein, which was further increased after the binding with saquinavir. 2022 Viruses Result HIV M46I 41 45 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Conventional molecular dynamics (MD) simulations were conducted on four systems, namely, wild-type HIV-1 protease (WT), saquinavir-bound wild-type HIV-1 protease (SQ-WT), M46I-mutation-carrying HIV-1 protease (MI), and saquinavir-bound M46I-mutation-carrying HIV-1 protease (SQ-MI). 2022 Viruses Result HIV M46I;M46I 171;236 175;240 PR;PR;PR;PR 105;153;200;265 113;161;208;273 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Conversely, the decreased H-bond pattern in the SQ-MI complex indicates that the M46I mutation inversely alters the structural rigidity of the protease upon saquinavir binding. 2022 Viruses Result HIV M46I 81 85 PR 143 151 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on Active Site Compactness. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on Conformational Compactness. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on Conformational Dynamics and Stability. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on Flap Curling and Opening. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on RMSD of the Backbone Atoms . 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on RMSD of the Backbone Atoms. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on Saquinavir-HIV-1 Binding Energetics. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on the Fluctuation of Amino Acid Residues . 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on the Fluctuation of Amino Acid Residues. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Effect of the M46I Mutation on the Hydrogen Bond Formation Pattern. 2022 Viruses Result HIV M46I 14 18 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Further, the molecular docking experiment revealed -12.2 and -11.16 docking scores for the saquinavir-bound wild-type and M46I-mutation-carrying HIV-1 protease, respectively. 2022 Viruses Result HIV M46I 122 126 PR 151 159 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. However, the M46I mutation altered this trend and highly reduced the significant involvement of energy contributory amino acids in the flap and active site regions of the protease (Figure 7D,E). 2022 Viruses Result HIV M46I 13 17 PR 171 179 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. In comparison to WT protease, saquinavir was unable to stabilize the flap motion in M46I protease. 2022 Viruses Result HIV M46I 84 88 PR;PR 20;89 28;97 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. In our study, larger fluctuations in the flap region of the M46I-mutated protein indicate a comparatively increased opening conformation. 2022 Viruses Result HIV M46I 60 64 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. In the last 35 ns of the simulation period (75-100 ns), the Rg value of the M46I structure reached close to the SQ-WT structure. 2022 Viruses Result HIV M46I 76 80 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. In the M46I-mutation-carrying protease, the binding of saquinavir was unable to maintain the minimum energy basin in comparison to the SQ-WT system. 2022 Viruses Result HIV M46I 7 11 PR 30 38 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Interestingly, the binding of saquinavir to the M46I protease increased the Rg value during the initial MD period (1-5 ns) in comparison to the unbound M46I structure. 2022 Viruses Result HIV M46I;M46I 48;152 52;156 PR 53 61 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Moreover, to explore the role of M46I mutation in saquinavir resistance in detail, the binding energy was decomposed per amino acid residue involved in the SQ-WT and SQ-MI complex formation, and the residues whose contribution were more than +-1 are depicted in Figure 7D,E, respectively. 2022 Viruses Result HIV M46I 33 37 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Overall the H-Bond pattern indicates that the M46I mutation decreased the rigidity of the protein structure and the strength of saquinavir binding to HIV-1 protease. 2022 Viruses Result HIV M46I 46 50 PR 156 164 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The amino acid contribution energy plot (Figure 7D,E) also indicated that the saquinavir interaction with the active site amino acid residues (Asp25, Thr26, Gly27, Asp124, Thr125, and Gly126) was decreased due to the M46I mutation. 2022 Viruses Result HIV M46I 217 221 Asp;Asp 143;164 146;167 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The Asp25-Asp124 distance was taken as a parameter to predict the compactness of the active site in the presence/absence of saquinavir in M46I-mutation-carrying proteases. 2022 Viruses Result HIV M46I 138 142 PR;Asp;Asp 161;4;10 170;7;13 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The binding free energy of the complex in the SQ-MI complex indicated about a 20% decrease (Table 1) in the energy, which might be responsible for the lesser anti-viral therapy outcome in the patients on saquinavir treatment carrying the M46I HIV-1 protease mutation. 2022 Viruses Result HIV M46I 238 242 PR 249 257 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The comparative interaction potential of saquinavir with the wild-type (SQ-WT) and M46I mutation-carrying (SQ-MI) HIV-1 protease was studied in terms of the binding free energy calculation. 2022 Viruses Result HIV M46I 83 87 PR 120 128 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The DCCM analysis results showed that the M46I mutation significantly increased both the correlated and anti-correlated motions in HIV protease in comparison to the WT structure. 2022 Viruses Result HIV M46I 42 46 PR 135 143 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The distance between Asp25-Ile50 and Asp-25-Ile149 residues was calculated to obtain insight into the role of M46I in the flap curling of the protease. 2022 Viruses Result HIV M46I 110 114 PR;Asp;Asp 142;21;37 150;24;40 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The FEL results also indicate that the M46I mutation provided increased conformational flexibility to the saquinavir-bound mutated protease. 2022 Viruses Result HIV M46I 39 43 PR 131 139 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The increased average Asp25-Ile50 distance in MI and SQ-MI (in comparison to WT and SQ-WT) indicates that the M46I mutation increased the curling of the flap. 2022 Viruses Result HIV M46I 110 114 Asp 22 25 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The increased distance in the saquinavir-unbound/bound M46I-mutation-carrying proteases indicates that the active site was less compact in comparison to the non-mutated systems. 2022 Viruses Result HIV M46I 55 59 PR 78 87 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The PCA results indicate that the M46I mutation significantly increased PC1 contribution, which might correlate with the increased flap movement in the protease. 2022 Viruses Result HIV M46I 34 38 PR 152 160 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The results indicate that the M46I mutation increases the RMSD of the backbone atoms in WT HIV-1 protease, which was further increased due to binding of an inhibitor molecule to the mutated protein. 2022 Viruses Result HIV M46I 30 34 PR 97 105 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The results indicate that the M46I-mutation-mediated structural change in the secondary structure of the flap region of the protein decreased the HIV-1 protease binding potential of saquinavir by lowering the van der Waals interaction. 2022 Viruses Result HIV M46I 30 34 PR 152 160 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The results showed that the M46I mutation caused the higher probability (0.07) for 144-148 degree angels in comparison to the WT structure where 146 degree angles showed a higher probability (Figure 4C). 2022 Viruses Result HIV M46I 28 32 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The results showed that the M46I mutation did not significantly affect the overall structure of the protein, except the flap region. 2022 Viruses Result HIV M46I 28 32 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The Rg value was markedly increased from the 12-50 ns period and was significantly higher than the unbound M46I structure. 2022 Viruses Result HIV M46I 107 111 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The saquinavir-bound M46I-mutation-carrying protease shifted the angle axis towards the right side of the plot (Figure 4D). 2022 Viruses Result HIV M46I 21 25 PR 44 52 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The secondary structure analysis showed that the M46I mutation significantly impacted the beta-sheet structures in HIV-1 protease. 2022 Viruses Result HIV M46I 49 53 PR 121 129 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The wild-type and M46I-mutation-carrying HIV-1 protease Pdb structures were overlapped, and the results are shown in Figure 1B. 2022 Viruses Result HIV M46I 18 22 PR 47 55 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. These data indicate that the M46I mutation differentially affects the energetics of saquinavir-HIV 1 protease in comparison to other known mutations. 2022 Viruses Result HIV M46I 29 33 PR 101 109 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. This indicates that the M46I mutation decreased the effect of saquinavir binding on the alteration of the PC1 contribution. 2022 Viruses Result HIV M46I 24 28 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Thus, it might be inferred that the M46I mutation results in increased dynamics at the flap region, which might affect the protease-binding efficacy of saquinavir. 2022 Viruses Result HIV M46I 36 40 PR 123 131 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. A total of 4.4% (20/460) of the sequences contained five different IN accessory mutations: -E157Q (2.39%), G163R/K (0.65%), Q95K (0.65%), T97A (0.43%), and G149A (0.22%). 2022 Viruses Result HIV E157Q;G149A;G163K;G163R;Q95K;T97A 92;156;107;107;124;138 97;161;114;114;128;142 IN 67 69 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Among the INSTI-mutation positions in the CCD residues that directly reduced the INTSI susceptibility, H51, T66, E92, F121, G140, Y143, Q146, S147, Q148, S153, N155, and E157Q were highly conserved, except for codon position E157Q, which was a polymorphic position (>1.0% variability). 2022 Viruses Result HIV E157Q;E157Q 170;225 175;230 INSTI 10 15 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. For subtype C, two transversions (minimum score of 5) were required to mutate to G140C (GGG/A to ATG/C); while for subtype B, one transversion and transition (minimum score: 3.5) were required to mutate to G140C (GGC to TGT). 2022 Viruses Result HIV G140C;G140C 81;206 86;211 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. However, a highly polymorphic residue in the CCD including V72I, I84M, F100Y, L101I, T112V, T124A, T125A, R127K, K136Q, D167E, K188R, and V201I was observed. 2022 Viruses Result HIV D167E;F100Y;I84M;K136Q;K188R;L101I;R127K;T112V;T124A;T125A;V201I;V72I 120;71;65;113;127;78;106;85;92;99;138;59 125;76;69;118;132;83;111;90;97;104;143;63 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. However, amino acid positions, D10E, S24N, D25E, V31I, and M50I were highly polymorphic (>20.0% variability). 2022 Viruses Result HIV D10E;D25E;M50I;S24N;V31I 31;43;59;37;49 35;47;63;41;53 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. However, one (0.22%) sequence from a person without previous ART exposure was found to harbor E92G, a mutation that moderately reduces EVG susceptibility but does not reduce susceptibility to RAL and DTG. 2022 Viruses Result HIV E92G 94 98 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. In addition, other mutations including M50I (18.5%, 85/460), L74I/M (2.8%, 13/460), S119R, (0.9%,4/460), V151I, (1.3%, 6/460), and D230N (0.4%, 2/460) were also detected. 2022 Viruses Result HIV D230N;L74I;L74M;M50I;S119R;V151I 131;61;61;39;84;105 136;67;67;43;89;110 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. In this study,19 substitutions conferring major resistance to DTG at 10 amino acid positions in the IN (T66A/I/K, E92G, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H, and R263K) were assessed to explore the genetic barrier to DTG. 2022 Viruses Result HIV E138A;E138K;E138T;E92G;G118R;G140A;G140C;G140S;N155H;Q148H;Q148K;Q148R;R263K;S147G;T66A;T66I;T66K;Y143C;Y143H;Y143R 127;127;127;114;120;138;138;138;178;167;167;167;189;160;104;104;104;149;149;149 136;136;136;118;125;147;147;147;183;176;176;176;194;165;112;112;112;158;158;158 IN 100 102 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. No major DRMs known to be associated with DTG resistance (T66K, E92Q, G118R, E138K/A/T, G140S/A/C, Q148H/R/K, N155H, or R263K) were detected among INSTI- naive individuals, regardless of previous exposure to ART. 2022 Viruses Result HIV E138A;E138K;E138T;E92Q;G118R;G140A;G140C;G140S;N155H;Q148H;Q148K;Q148R;R263K;T66K 77;77;77;64;70;88;88;88;110;99;99;99;120;58 86;86;86;68;75;97;97;97;115;108;108;108;125;62 INSTI 147 152 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Only one accessory mutation per sequence was detected, except for one sequence with two (G149A and E157Q) accessory mutations. 2022 Viruses Result HIV E157Q;G149A 99;89 104;95 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Our analysis also showed that 24 amino acid positions were highly polymorphic (>20.0% variability): D10E, K14R, S24N, D25E, V31I, M50I, V72I, I84M, F100Y, L101I, T112V, T124A, T125A, R127K, K136Q, D167E, K188R, V201I, K215N, T218I, A265V, R269K, D278A, and S283G. 2022 Viruses Result HIV A265V;D10E;D167E;D25E;D278A;F100Y;I84M;K136Q;K14R;K188R;K215N;L101I;M50I;R127K;R269K;S24N;S283G;T112V;T124A;T125A;T218I;V201I;V31I;V72I 232;100;197;118;246;148;142;190;106;204;218;155;130;183;239;112;257;162;169;176;225;211;124;136 237;104;202;122;251;153;146;195;110;209;223;160;134;188;244;116;262;167;174;181;230;216;128;140 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Similarly, a two-point mutation (one transversion and one transition) (minimum score of 3.5) was required to mutate to G140S (GGG/A to AGT/C) for subtype C; while subtype B required a one-step transition (minimum score of 1) (GGC to AGC). 2022 Viruses Result HIV G140S 119 124 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Similarly, our comparison of the consensus sequences from the HIVDR and non-HIVDR groups also showed high similarity between the two consensus sequences, except at positions K215N, T218L, and R269, where the HIVDR group had one amino acid; while the no-HIVDR group had a mixture of amino acids at positions T215K/N, T218I/L, and R269R/K, respectively (Figure 3). 2022 Viruses Result HIV K215N;R269K;R269R;T215K;T215N;T218I;T218L;T218L 174;329;329;307;307;316;181;316 179;336;336;314;314;323;186;323 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Six of these (D10E, K14R, S24N, D25E, V31I, and M50I) belonged to the NTD, whereas 12 (V72I, I84M, F100Y, L101I, T112V, T124A, T125A, R127K, K136Q, D167E, K188R, and V201I) belonged to the CCD, and the other 6 (K215N, T218I, A265V, R269K, D278A, and S283G) belonged to the CTD. 2022 Viruses Result HIV A265V;D10E;D167E;D25E;D278A;F100Y;I84M;K136Q;K14R;K188R;K215N;L101I;M50I;R127K;R269K;S24N;S283G;T112V;T124A;T125A;T218I;V201I;V31I;V72I 225;14;148;32;239;99;93;141;20;155;211;106;48;134;232;26;250;113;120;127;218;166;38;87 230;18;153;36;244;104;97;146;24;160;216;111;52;139;237;30;255;118;125;132;223;171;42;91 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Within CTD, the two large consecutive residues, L241-Q252 and I257-K264, which are involved in the binding of viral and cellular DNA, were found to be highly conserved, except for positions I251 and V257, which were mutated to I251L and V259I in 3.5% and 0.7% of the sequences, respectively. 2022 Viruses Result HIV I251L;V259I 227;237 232;242 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Several sequence variations exist between Tat Subtype B and subtype C, however key sequence variants with a reported effect on neurocognitive outcomes include C31S, R57S, Q63E. 2022 Frontiers in microbiology Result HIV C31S;Q63E;R57S 159;171;165 163;175;169 Tat 42 45 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Using Tat Subtype B as the positive control, from the hotspot residues, it is relevant to note that subtype C differs at position 40 with a K40Y mutation and 57 with R57S mutation. 2022 Frontiers in microbiology Result HIV K40Y;R57S 140;166 144;170 Tat 6 9 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Interestingly, the mutations N255D or N265D do not affect sensitivity to any of the NRTIs or NNRTIs tested which is a useful feature if the same mutations were to arise in response to treatment with anti-RT aptamer RNAs via gene therapy in the future. 2005 AIDS research and therapy Conclusion HIV N255D;N265D 29;38 34;43 NNRTI;NRTI;RT 93;84;204 99;89;206 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. The mutations N255D and N265D both conferred resistance to two of the 5 new DNA aptamers (with the exception of RT8) and 1 RNA aptamer tested suggesting that the N255 and N265 residues probably serve as contact points for most aptamers. 2005 AIDS research and therapy Conclusion HIV N255D;N265D 14;24 19;29 RT 112 114 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. In addition, this evolution route requires a relatively difficult transversion type of mutation (G-to-T), whereas the G431R mutation is made by a simple transition type mutation (G-to-A). 2006 Retrovirology Conclusion HIV G431R 118 123 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. In order to directly test the effect of the G431R mutation, we introduced it back into the original GIA-SKY T20-dependent molecular clone. 2006 Retrovirology Conclusion HIV G431R 44 49 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Interestingly, the G431R mutation has previously been selected in long-term cultures of a translationally impaired HIV-1 mutant. 2006 Retrovirology Conclusion HIV G431R 19 24 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. It would be interesting to investigate if our GIA-SKY-G431R revertant, which has reduced sensitivity to sCD4 and increased sensitivity to HR1 antibodies, may be such a possible vaccine candidate. 2006 Retrovirology Conclusion HIV G431R 54 59 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Replication assays in SupT1 cells confirmed that the G431R mutation is sufficient to restore replication in the absence of T20. 2006 Retrovirology Conclusion HIV G431R 53 58 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Strikingly, 3 evolution cultures contained identical escape variants with the same glycine-to-arginine substitution at position 431 of Env (all identical codon changes GGA-to-AGA). 2006 Retrovirology Conclusion HIV G431R 83 131 Env 135 138 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The combined results of the reduced sensitivity to sCD4 and increased sensitivity to D5-IgG1 suggest that the G431R mutation partially restores gp41 function of this Env protein by modifying the Env-CD4 interaction and gp41 conformational changes, thus preventing or modulating the premature switch to the 6-helix bundle similar to the effect of the T20 peptide on this mutant. 2006 Retrovirology Conclusion HIV G431R 110 115 gp41;gp41;Env;Env 144;219;166;195 148;223;169;198 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The G431R mutation could similarly restore gp41 function by preventing the abortive premature switch in gp41. 2006 Retrovirology Conclusion HIV G431R 4 9 gp41;gp41 43;104 47;108 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. This implies that the G431R substitution is selected as an alternative solution to the conformational gp41 defect of the GIA-SKY mutant, which is normally controlled by T20. 2006 Retrovirology Conclusion HIV G431R 22 27 gp41 102 106 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. In other words, the detection of K65R may by itself not be a valid reason to withdraw tenofovir from the patient's regimen, unless more effective salvage regimens, which are also feasible in terms of cost, toxicity and compliance are available. 2007 Retrovirology Conclusion HIV K65R 33 37 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Such information is also relevant to develop treatment guidelines for resource-poor areas, where access to 2nd or 3rd line anti-HIV drugs may be limited, and regular monitoring of virus levels and drug resistance (such as K65R) is not always feasible. 2007 Retrovirology Conclusion HIV K65R 222 226 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The current findings with RT-SHIV are consistent with but also extend previous observations on the K65R mutation in the SIV model, with the novel observation of the tenofovir-selected K70E mutation (which was not detected by population sequencing in tenofovir-treated SIVmac251-infected macaques). 2007 Retrovirology Conclusion HIV K65R;K70E 99;184 103;188 RT 26 28 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The observations in macaques suggest that for persons infected with K65R HIV-1, both immune-mediated and drug-dependent antiviral activities may play a role in controlling viremia, and that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be beneficial, particularly when assisted by antiviral immune responses. 2007 Retrovirology Conclusion HIV K65R;K65R 68;214 72;218 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. While preliminary data already suggest the virologic benefits of including tenofovir in drug regimens for HIV-1 infected patients with K65R mutants, additional long-term studies are warranted to determine also the potential clinical benefits of continuing tenofovir therapy in the presence of K65R mutants. 2007 Retrovirology Conclusion HIV K65R;K65R 135;293 139;297 HIV infections 106 120 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. For clinical management it is important to be aware of novel resistance patterns such as the one conferred by the E40F that is currently not represented in the algorithms that are used to manage patients failing nucleoside therapies. 2008 Retrovirology Conclusion HIV E40F 114 118 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. We have identified a novel resistance (E40F) and compensatory (K43E) amino acid change in HIV-1 RT. 2008 Retrovirology Conclusion HIV E40F;K43E 39;63 43;67 RT 96 98 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. However, regarding the sensitivity to entry inhibitors, although there is a clear relationship between macrophage tropism and diminished sensitivity to BMS-378806 (similarly to Peters et al.), this is not the case with HNG-105, since some macrophage-tropic Env (Bv1v3, Bv1v2, BaL) show reduced sensitivity similar to the non-macrophage tropic Env SPL and SB, and quite different from the other macrophage-tropic Env, BR, BR(N283T), BS, DS17 and DS17(N283T). 2008 Retrovirology Conclusion HIV N283T;N283T 424;450 429;455 Env;Env;Env 257;343;412 260;346;415 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. At the helix 2 region, the W184A mutation is known to abolish HIV CA protein assembly in vitro. 2009 Biomacromolecules Conclusion HIV W184A 27 32 Capsid 66 68 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. The Q155N and E159D mutations at the MHR greatly destabilize the binding affinity of the CA dimer by disrupting the hydrogen bonding network between the loop and the helix 1 and 2 motifs. 2009 Biomacromolecules Conclusion HIV E159D;Q155N 14;4 19;9 Capsid 89 91 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Both subtype B and subtype C RTs containing K65R are less able to bind to TFV-DP and are less susceptible than WT RTs to the chain-terminating effects of this compound. 2009 Retrovirology Conclusion HIV K65R 44 48 RT;RT 29;114 32;117 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In particular, both enzymes, when containing K65R, share a diminished initiation efficiency at low dNTP concentrations as well as diminished rates of excision if K65R is present. 2009 Retrovirology Conclusion HIV K65R;K65R 45;162 49;166 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Our results show that an enzyme-based mechanism is not the basis for the higher propensity of HIV-1 subtype C to acquire the K65R mutation in response to NRTI exposure and that subtype B and C RTs behave similarly in regard to most enzymatic properties. 2009 Retrovirology Conclusion HIV K65R 125 129 NRTI;RT 154;193 158;196 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Constructs containing a single carbohydrate-binding domain, but capable of forming domain swapped dimers either through a wild type hinge region, such as m4-CVN, or by specific hinge region mutations, such as S52P-m4-CVN and DeltaQ50-m4-CVN, are functional. 2009 Biopolymers Conclusion HIV S52P 209 213 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Monovalent, monomeric mutants of CV-N (P51G-m4-CVN and CVNMutDB) are inactive in inhibiting viral entry in the range of concentrations tested and bind gp120 with greatly reduced affinity. 2009 Biopolymers Conclusion HIV P51G 39 43 gp120 151 156 19235857 Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. Mutants containing two or more binding sites, such as wt CV-N, S52P-CVN, and DeltaQ50-CVN, are functional at low-nanomolar concentrations. 2009 Biopolymers Conclusion HIV S52P 63 67 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Three crystal structures of RT were used in order to find NNRTIs that would be effective against both wild-type HIV-1 and variants possessing the clinically troublesome Y181C RT mutation. 2009 Journal of chemical information and modeling Conclusion HIV Y181C 169 174 NNRTI;RT;RT 58;28;175 64;30;177 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Three of the compounds showed low-micromolar anti-viral activity towards either or both the wild-type and Y181C HIV-1 strains. 2009 Journal of chemical information and modeling Conclusion HIV Y181C 106 111 19374380 Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures. Two of the structures, 1rt4 and 2be2, are for WT-virus with different conformations of Tyr181, while the third structure, 1jla, incorporates the Y181C modification. 2009 Journal of chemical information and modeling Conclusion HIV Y181C 145 150 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Biochemical and structural data have elucidated two distinct mechanisms of NRTI resistance of 1) discrimination due to steric hindrance by M184V/I mutation to 3TC-TP and emtricitabine-TP and 2) the ATP-mediated excision of incorporated NRTIs exemplified by the TAMs, which is the primary mechanism of resistance to AZT. 2009 The Journal of biological chemistry Conclusion HIV M184I;M184V 139;139 146;146 NRTI;NRTI 75;236 79;241 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The effect of K65R appears to be on the rate-limiting conformational step of nucleotide incorporation; this idea is supported by the lack of an elemental effect that would also affect the excision reaction. 2009 The Journal of biological chemistry Conclusion HIV K65R 14 18 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R mutation neither enhances nor reduces the interaction of dATP or TFV-DP in the precatalytic complexes with RT; rather, the side chain of K65R has an enhanced interaction with the side chain of Arg72 to form a molecular platform that restricts adaptability of the polymerase active site and causes both a decreased rate of substrate incorporation and NRTI excision. 2009 The Journal of biological chemistry Conclusion HIV K65R;K65R 4;146 8;150 Pol;NRTI;RT 272;359;116 282;363;118 19840380 Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. Our results moreover highlight partial tailed variants 1-279/F185K and 1-276/F185K as viable candidates for structural biology studies, as they retained >20% of IN enzymatic activities yet lacked at least half of the disordered region. 2009 Retrovirology Conclusion HIV F185K;F185K 61;77 66;82 IN 161 163 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Etravirine is a newer generation NNRTI with proven efficacy against HIV-1, which has developed resistance to earlier NNRTIs, including mutants with single K103N and Y181C mutations. 2008 Future HIV therapy Conclusion HIV K103N;Y181C 155;165 160;170 NNRTI;NNRTI 33;117 38;123 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Etravirine RAMs include V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S and M230L. 2008 Future HIV therapy Conclusion HIV A98G;E138A;G190A;G190S;K101E;K101H;K101P;L100I;M230L;V106I;V179D;V179F;V179T;V90I;Y181C;Y181I;Y181V 30;61;90;90;43;43;43;36;102;54;68;68;68;24;79;79;79 34;66;97;97;52;52;52;41;107;59;77;77;77;28;88;88;88 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Mutations most commonly associated with significant etravirine resistance include Y181I, Y181V, K101P and M230L, which were rarely present in clinical isolates. 2008 Future HIV therapy Conclusion HIV K101P;M230L;Y181I;Y181V 96;106;82;89 101;111;87;94 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In summary, we have demonstrated that both virion infectivity and proteolytic stability of RT with p51 RNH cleavage site mutations can be restored to various extents by the second-site compensatory mutation T477A. 2010 Retrovirology Conclusion HIV T477A 207 212 RT 91 93 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Studies are currently in progress to characterize the C-terminal amino acid sequence of the RT p51 subunit from HIV-1 with p51 RNH cleavage site mutations and the T477A substitution in RT in order to determine whether this compensatory mutation enables proteolytic cleavage at a position other than the normal F440 Y441 location. 2010 Retrovirology Conclusion HIV T477A 163 168 RT;RT 92;185 94;187 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. In fact, in the Stanford University HIV Database, N348I is frequently observed in viruses from patients failing combination antiretroviral therapies that contained an NNRTI and either AZT/3TC (frequency of N348I = 22.2%) or AZT/ddI (frequency of N348I = 9.5%). 2010 AIDS (London, England) Conclusion HIV N348I;N348I;N348I 50;206;246 55;211;251 NNRTI 167 172 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. This finding is consistent with recent studies that show a strong association between N348I with TAMs, M184V/I and Y181C or that N348I is frequently observed in AZT- and/or ddI-containing therapies. 2010 AIDS (London, England) Conclusion HIV M184I;M184V;N348I;N348I;Y181C 103;103;86;129;115 110;110;91;134;120 20160634 N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations. This study suggests that the acquisition of N348I in HIV-1 RT, which can occur early during therapy oftentimes before TAMs, may provide a simple genetic pathway that allows the virus to select both TAMs and mutations that are antagonistic to TAMs (e.g. 2010 AIDS (London, England) Conclusion HIV N348I 44 49 RT 59 61 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. A signature mutational motif in subtype C accelerates K65R selection. 2009 HIV therapy Conclusion HIV K65R 54 58 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Barrier to K65R is regimen associated. 2009 HIV therapy Conclusion HIV K65R 11 15 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Bidirectional antagonism of TAMs and K65R pathways lead to a counter selection of K65R in AZT/d4T-experienced patients. 2009 HIV therapy Conclusion HIV K65R;K65R 37;82 41;86 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Clinical trials with triple nucleoside reverse-transcriptase inhibitors (NRTIs) regimens were discontinued due to virological failure with high rates of K65R. 2009 HIV therapy Conclusion HIV K65R 153 157 NRTI;NRTI 28;73 60;78 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Elevated K65R selection in resource-limited settings may be related to suboptimal ddI, d4T and NVP regimens. 2009 HIV therapy Conclusion HIV K65R 9 13 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Higher frequencies of K65R are linked to suboptimal ddI and d4T regimens. 2009 HIV therapy Conclusion HIV K65R 22 26 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Inclusion of AZT may offset virological failure and K65R resistance in two-four NRTI regimens containing K65-selecting drugs. 2009 HIV therapy Conclusion HIV K65R 52 56 NRTI 80 84 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Increased selection of K65R with nevirapine (NVP) is associated with the Y181C and/or G190A mutations. 2009 HIV therapy Conclusion HIV G190A;K65R;Y181C 86;23;73 91;27;78 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. K65R confers partial resistance to most nucleoside analogs while remaining susceptible to zidovudine (AZT). 2009 HIV therapy Conclusion HIV K65R 0 4 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. K65R is selected by tenofovir disoproxil fumarate (TDF), abacavir, didanosine (ddI), stavudine (d4T) and amdoxovir. 2009 HIV therapy Conclusion HIV K65R 0 4 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. K65R is selected in 9-30% of subtype C patients failing therapy in Africa. 2009 HIV therapy Conclusion HIV K65R 0 4 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. K65R resistance pathway. 2009 HIV therapy Conclusion HIV K65R 0 4 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Optimizing NRTI and NRTI/non-NRTI regimens deter the emergence of K65R. 2009 HIV therapy Conclusion HIV K65R 66 70 NNRTI;NRTI;NRTI 25;11;20 33;15;24 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Recent clinical trials are evaluating the efficacy of quadruple-NRTI analog combinations as TAM/K65R-sparing regimens. 2009 HIV therapy Conclusion HIV K65R 96 100 NRTI 64 68 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The favorable barrier to K65R development makes TDF-based regimens leading candidates for microbicides and pre- and postexposure prophylaxis. 2009 HIV therapy Conclusion HIV K65R 25 29 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The infrequent development of K65R in drug-naive and treatment-experienced patients is due to impaired K65R replicative capacity and fitness constraints imposed by K65R and M184V - associated with resistance to lamivudine (3TC) and emtricitabine (FTC) and regimen potency (e.g., TDF-FTC). 2009 HIV therapy Conclusion HIV K65R;K65R;K65R;M184V 30;103;164;173 34;107;168;178 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The overall incidence of K65R is in 1-4% of the genotyped population. 2009 HIV therapy Conclusion HIV K65R 25 29 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. And, the calculations correctly predict L33Q and Q40K mutations will be most detrimental. 2010 Biochemistry Conclusion HIV L33Q;Q40K 40;49 44;53 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. As a result, unfavorable DeltaDeltaEcoul and solvent-mediated electrostatics (DeltaDeltaGelec) for the negatively charged V38E mutation are significantly more unfavorable than other mutations (Table 3). 2010 Biochemistry Conclusion HIV V38E 122 126 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. As L33S is the only mutation leading to a smaller sidechain the offset is probably linked to differences in size and associated entropic effects not accounted for in the calculations. 2010 Biochemistry Conclusion HIV L33S 3 7 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. From more quantitative points of view, additional simulations of T20 in complex with the gp41 coiled-coil containing L33Q, L33S, G36V, I37K, V38E, Q40H, and Q40K point mutations correctly lead to decreases in binding (Tables 3). 2010 Biochemistry Conclusion HIV G36V;I37K;L33Q;L33S;Q40H;Q40K;V38E 129;135;117;123;147;157;141 133;139;121;127;151;161;145 gp41 89 93 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. In contrast, FR trends for the neutral L33S and L33Q mutations appear to be due to differences in the final state (Figure 11) as a result of suboptimal packing of glutamine relative to the smaller serine sidechain. 2010 Biochemistry Conclusion HIV L33Q;L33S 48;39 52;43 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Interestingly, all mutations but one lead to reduced van der Waals interactions (Table 3) and the greatest losses occur for the two positively charged mutations (I37K, Q40K). 2010 Biochemistry Conclusion HIV I37K;Q40K 162;168 166;172 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Interestingly, results for L33S are offset from the other six datapoints although in an absolute sense the magnitude DeltaDeltaGFR calcd is in good agreement. 2010 Biochemistry Conclusion HIV L33S 27 31 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Origins of the difference in experimentally observed fold resistance (FR) for I37K (less detrimental) vs Q40K (more detrimental) mutations was traced to initial wildtype interactions (Figure 12) involving a polar/charged patch on T20. 2010 Biochemistry Conclusion HIV I37K;Q40K 78;105 82;109 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. The model geometry is also consistent with recent experimental results reporting T20 mutations which enhanced (T128I) or reduced (L152A, D153A, W155A, and A156Q) binding. 2010 Biochemistry Conclusion HIV A156Q;D153A;L152A;T128I;W155A 155;137;130;111;144 160;142;135;116;149 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Hence the T8Delta mutant exhibits intermediate resistance to BVM while T8A retains BVM susceptibility. 2010 Retrovirology Conclusion HIV T8A 71 74 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. In particular, the SP1-V7A polymorphism constitutes a significant obstacle as it displayed robust BVM-resistance in in vitro assays and has been shown to occur at high frequency in some HIV-1 subtypes. 2010 Retrovirology Conclusion HIV V7A 23 26 SP1 19 22 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Mutations SP1-V7M and T8Delta exhibited an intermediate level of BVM susceptibility. 2010 Retrovirology Conclusion HIV V7M 14 17 SP1 10 13 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The SP1-Q6A, Q6H, and T8A mutants retained complete sensitivity to BVM. 2010 Retrovirology Conclusion HIV Q6H;T8A;Q6A 13;22;8 16;25;11 SP1 4 7 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The SP1-V7A mutant displayed full resistance to BVM in terms of CA-SP1 processing, single-cycle infectivity, and virus replication assays, and its resistance was comparable to that of the robust and frequently observed BVM-resistance mutant SP1-A1V. 2010 Retrovirology Conclusion HIV A1V;V7A 245;8 248;11 SP1;SP1;SP1;Capsid 4;67;241;64 7;70;244;66 20406463 Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. The SP1-V7M mutant appeared less susceptible to BVM than did SP1-T8Delta; SP1-V7M BVM-treated virions accumulated less unprocessed CA-SP1 and the SP1-V7M virus replicated without acquisition of additional mutations at 50 ng/ml BVM, whereas robust SP1-T8Delta replication required acquisition of a previously characterized BVM-resistance mutation. 2010 Retrovirology Conclusion HIV V7M;V7M;V7M 8;78;150 11;81;153 SP1;SP1;SP1;SP1;SP1;SP1;Capsid 4;61;74;134;146;247;131 7;64;77;137;149;250;133 20655872 Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. In the A18H mutant of Vpu the TM helix tilt appears to be greater than for AM2 and, while rimantadine binds, the mechanism by which it binds appears to be very different from that for AM2, where drug binding induces a helix kink and much more significant shifts in the PISEMA resonances. 2011 Biochimica et biophysica acta Conclusion HIV A18H 7 11 Vpu 22 25 20655872 Drug sensitivity, drug-resistant mutations, and structures of three conductance domains of viral porins. While AM2 and BM2 form proton channels, wild-type Vpu has no such specificity, but with a single site mutation, A18H, it forms proton specific channels that are sensitive to rimantadine. 2011 Biochimica et biophysica acta Conclusion HIV A18H 112 116 Vpu 50 53 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. A G913A (E42K) mutation in MA and a C1907T (P10L) mutation in SP1 were responsible for the enhanced infectivity of NLDeltaSL1 in PM-1 cells through partially restoring the packaging specificity of viral RNA. 2010 Retrovirology Conclusion HIV C1907T;E42K;G913A;P10L 36;9;2;44 42;13;7;48 SP1;Matrix 62;27 65;29 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. on one of their patients, would indicate that persistence of the K103N mutation as a majority quasispecies may ensue after a very short exposure to EFV, in the absence of wild type depletion, likely providing relative replicative advantage. 2009 Journal of medical case reports Conclusion HIV K103N 65 70 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Our case therefore suggests that the presence of the K103N mutation should be ruled out even after minimal exposures to EFV, reinforcing at the same time the need for a systematic evaluation of GRT in naive patients and after any type of interruption of NNRTI-based HAART regimens, as well as the need for a wise strategy of NNRTI interruption. 2009 Journal of medical case reports Conclusion HIV K103N 53 58 NNRTI;NNRTI 254;325 259;330 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. These proved that HIV infection was due to clade B HIV-1, both yielding an identical sequence pattern, with the isolate presence of the K103N mutation in the prevalent strain (Table 1). 2009 Journal of medical case reports Conclusion HIV K103N 136 141 HIV infections 18 31 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Moreover, we report for the first time the selection of two mutations, Q91R and I175M, under RAL selective pressure. 2010 Retrovirology Conclusion HIV I175M;Q91R 80;71 85;75 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Phenotypic assays with the Q91R + I175M ROD double mutant confirmed the role of these mutations in resistance to RAL showing that they account for a 13-fold decrease in susceptibility to RAL. 2010 Retrovirology Conclusion HIV I175M;Q91R 34;27 39;31 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. As both the double mutants are attenuated in comparison to WT and single point mutants (K65R, L74V and L74I) and RTs containing mutations K65R+L74V or K65R+L74I have decreased processivity, our results provide the explanation for the rarity of these double mutants in clinical settings. 2011 Virology journal Conclusion HIV K65R;K65R;K65R;L74I;L74I;L74V;L74V 88;138;151;103;156;94;143 92;142;155;107;160;98;147 RT 113 116 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In summary, we demonstrated here that in contrast to L74V, the L74I mutation in the background of K65R results in a replication competent virus due to an increased processivity of RT. 2011 Virology journal Conclusion HIV K65R;L74I;L74V 98;63;53 102;67;57 RT 180 182 21276267 Interplay between HIV entry and transportin-SR2 dependency. The role of CA in nuclear import of viruses which retain their natural envelopes also warrants further study, since the N74D CA mutant is less dependent on TRN-SR2 for infection. 2011 Retrovirology Conclusion HIV N74D 120 124 Env;Capsid;Capsid 71;12;125 80;14;127 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? As shown in Table 3, failure of therapy in L76V-positive patients with ATV and/or SQV containing therapy was noticeable associated with an additional establishment of the protease gene mutation at position L90 M which resulted in resistance against all available PIs. 2011 AIDS research and therapy Conclusion HIV L76V;L90M 43;206 47;211 PR;PI 171;263 179;266 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Nevertheless, since there are still distinct discrepancies, mostly overestimation of resistance, in the prediction of the resistance level for Atazanavir and Saquinavir in five of the most common genotypic interpretation systems, there is still a need for further evaluation in the case of L76V occurrence. 2011 AIDS research and therapy Conclusion HIV L76V 290 294 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Six of eight patients who received a second genotypic resistance test following therapy failure were diagnosed positive for L90 M. 2011 AIDS research and therapy Conclusion HIV L90M 124 129 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? The strategy of combining mutation-selecting drugs with "resensitized" drugs has already been discussed for the reverse transcriptase mutation M184V in NRTI-containing therapies and has also been shown to be an adequate option for a couple of other mutations including the mutation N88 S. 2011 AIDS research and therapy Conclusion HIV M184V;N88S 143;282 148;287 RT;NRTI 112;152 133;156 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Thus, it might be questionable if SQV, which primarily selects L90 M should be replaced in favour of ATV. 2011 AIDS research and therapy Conclusion HIV L90M 63 68 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. As shown in this study and other previous reports, the presence of the Q151M mutation significantly limits the options for second-line therapies as the Q151M-containing virus remains only susceptible to one approved NRTI, TDF. 2011 Retrovirology Conclusion HIV Q151M;Q151M 71;152 76;157 NRTI 216 220 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Our results showed that the Q151M MDR takes a long time to develop and keeping patients on failing NRTI therapy could be facilitating its emergence. 2011 Retrovirology Conclusion HIV Q151M 28 33 NRTI 99 103 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The Q151M MDR is also often linked to other NRTI and NNRTI mutations which develop earlier and thus further limiting the options for second-line regimens. 2011 Retrovirology Conclusion HIV Q151M 4 9 NNRTI;NRTI 53;44 58;48 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Understanding the evolution and molecular mechanisms leading to the emergence of the Q151M MDR complex is important especially in light of its relatively frequent occurrence in some ARV rollout cohorts. 2011 Retrovirology Conclusion HIV Q151M 85 90 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. In further studies, 11 also showed nanomolar activity against resistant viral strains, except for the M184V single mutation. 2011 European journal of medicinal chemistry Conclusion HIV M184V 102 107 21745701 Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. The hydrochloride salt 11 retained its sub-nanomolar activity against NRTI-resistant (K101E) and multi-drug-resistant HIV strains (RTMDR). 2011 European journal of medicinal chemistry Conclusion HIV K101E 86 91 NRTI 70 74 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. The key goal was to obtain anti-viral agents with high potency towards variant forms of HIV-1 that incorporate the clinically important Tyr181Cys mutation in HIV reverse transcriptase. 2011 Journal of the American Chemical Society Conclusion HIV Y181C 136 145 RT 162 183 21853995 Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase. With guidance from the computations, it was possible to progress from the parent phenoxy-containing 3 with micromolar activity to the extremely potent analogs 36 and 37 with low-nanomolar potency against both wild-type HIV-1 and the Tyr181Cys variant. 2011 Journal of the American Chemical Society Conclusion HIV Y181C 233 242 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. In conclusion, this study confirms that HIV-2 resistance to RAL is due to the N155H, G140S/Q148R or E92Q/Y143C mutations in the IN coding region. 2011 Retrovirology Conclusion HIV E92Q;G140S;N155H;Q148R;Y143C 100;85;78;91;105 104;90;83;96;110 IN 128 130 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The N155H and G140S/Q148R mutations make similar contributions to resistance in both HIV-1 and HIV-2, but Y143C alone is not sufficient to account for the resistance of HIV-2 genomes harboring this mutation. 2011 Retrovirology Conclusion HIV G140S;N155H;Q148R;Y143C 14;4;20;106 19;9;25;111 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. It should be noted, however, that the interpretation of our data is limited by our inability to purify and characterize p66WT/p51N348I HIV-1 RT. 2011 Retrovirology Conclusion HIV N348I 129 134 RT 141 143 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. The molecular modelling suggests that the N348I mutation abrogates an interaction between the beta14-beta15 loop in the p51 subunit of RT and the RNA template, which may explain the observed decrease in the secondary or polymerase independent RNase H cleavages. 2011 Retrovirology Conclusion HIV N348I 42 47 Pol;RT 220;135 230;137 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. This study demonstrates that N348I-mediated AZT and nevirapine resistance is likely due to the mutation in the p51 subunit of RT. 2011 Retrovirology Conclusion HIV N348I 29 34 RT 126 128 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Although the second-generation inhibitor, MK-0536 is more effective against these mutations, the new compound showed a smaller loss of potency when challenged with vectors carrying the G140S/Q148H mutations. 2012 Chemical biology & drug design Conclusion HIV G140S;Q148H 185;191 190;196 22107736 Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. In in vivo antiviral assays a representative member of the new series had a much smaller reduction in potency than raltegravir when challenged with vectors carrying the G140S/Q148H, Y143R and N155H mutations. 2012 Chemical biology & drug design Conclusion HIV G140S;N155H;Q148H;Y143R 169;192;175;182 174;197;180;187 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. The present study indicates that IN mutants W131A and Q168L previously shown to be defective for LEDGF/p75 were also impaired for TNPO3 binding, albeit to a lesser extent. 2011 Retrovirology Conclusion HIV Q168L;W131A 54;44 59;49 IN 33 35 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. As for the other protease inhibitors, the increase of the binding affinity implies that the double mutant I50L/A71V may be well adapted by the TMC114. 2012 The journal of physical chemistry. B Conclusion HIV A71V;I50L 111;106 115;110 PR 17 25 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. However, for the double mutant I50L/A71V, the increase in the binding affinity can be mainly attributed to the increase in electrostatic and van der Waals energies of residues Leu50 and Leu50' with considerable aid from the other flap residues Gly49', Ile47' and active site residue Ile84. 2012 The journal of physical chemistry. B Conclusion HIV A71V;I50L 36;31 40;35 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. On the basis of the structural energetic analysis, we can conclude that the direct effects by the decrease in van der Waals energies for residues Val50 and Val50' and the increase in polar solvation energy for Val50' mainly accomplish the drug resistance in I50V mutant. 2012 The journal of physical chemistry. B Conclusion HIV I50V 258 262 22239286 Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. The double mutant I50L/A71V HIV-pr exhibits different conformation and dynamic behavior to the TMC114 inhibitor, e.g., closer movement of flaps, and flip-flop interaction between the catalytic Asp25 OD1/OD2 atoms and O18 of TMC114, which may imply less drug resistance, which was further verified in terms of binding affinity to the inhibitor in the energetic calculation. 2012 The journal of physical chemistry. B Conclusion HIV A71V;I50L 23;18 27;22 Asp;PR 193;32 196;34 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Overall, the phenotype observed in the present study for Envs containing the cluster of mutations V38A+N140I, which maintained fusion capacity, but had a decreased ability to deplete CD4+ T cells, correlated with the observed in vivo data in patients, including a maintenance of viral load with an increase in CD4 counts. 2012 Retrovirology Conclusion HIV N140I;V38A 103;98 108;102 Env 57 61 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. In this study, we found that Y181C remarkably improved the IC50 to NVP, although the novel mutation H221Y only slightly conferred resistance to NVP, when it combined with Y181C, the phenotypic drug resistance folds were improved extremely. 2012 AIDS research and treatment Conclusion HIV H221Y;Y181C;Y181C 100;29;171 105;34;176 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. There was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype containing dhps 581 and dhps S436H in the parasites from pregnant women in western Kenya over 13 years. 2012 Malaria journal Conclusion HIV S436H 126 131 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The mutations H105Y, V255M, S375R/N, G471R/E, and D474N are found to be of importance for resistance towards the miniCD4 proteins, M48 and M48U1, in subtype B viruses. 2012 Retrovirology Conclusion HIV D474N;G471E;G471R;H105Y;S375N;S375R;V255M 50;37;37;14;28;28;21 55;44;44;19;35;35;26 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. Even though M184V and L63P continue to be the most prevalent mutations for the reverse transcriptase and the protease genes, respectively, a descending trend was observed for most of the mutations. 2012 AIDS research and treatment Conclusion HIV L63P;M184V 22;12 26;17 RT;PR 79;109 100;117 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. However, the information on the potential importance of Thr-44 led us to create a Nef clone with a T44A mutation and test it in the secretion assay. 2012 Journal of molecular modeling Conclusion HIV T44A 99 103 Nef 82 85 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. phi plot) for the amino acids comprising the SMR (plus Thr-44), our WT MD SMR had a higher proportion of amino acids within the favored region, while the mutant (Val-65 to Ala substitution) had a greater number of amino acid residues outside the accepted range. 2012 Journal of molecular modeling Conclusion HIV V65A 162 176 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. These in silico observations were further supported by the RMSD analysis which showed that the WT SMR (VGFPV) MD-generated structure fell within accepted limits (less than 4 A) while the mutant Nef V66A SMR structure was outside this accepted range, as compared to the lowest energy structure generated by MD experiments. 2012 Journal of molecular modeling Conclusion HIV V66A 198 202 Nef 194 197 22643973 Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. We hypothesized that comparative computer modeling analysis of the conserved SMR motif of HIV-1 Nef in both wild-type and V66A mutant proteins would yield valuable information concerning the effect of SMR mutations upon Nef protein structure; reasoning that, since the Nef SMR motif is highly conserved among HIV-1 isolates, its sequence might be critical for the structural integrity and function of the HIV-1 Nef protein. 2012 Journal of molecular modeling Conclusion HIV V66A 122 126 Nef;Nef;Nef;Nef 96;220;269;411 99;223;272;414 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Biochemical studies with WT and mutant HIV-1 RTs showed that the impact of R284K on nucleotide discrimination or ATP-mediated excision of chain-terminated primers was not significant. 2012 Retrovirology Conclusion HIV R284K 75 80 RT 45 48 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. However, in the presence of the M41L/L210W/T215Y complex, R284K increases the catalytic rate of nucleotide incorporation and the RNase H activity of the RT, and these effects promote chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes. 2012 Retrovirology Conclusion HIV L210W;M41L;T215Y;R284K 37;32;43;58 42;36;48;63 RT 153 155 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. M41L/L210W/T215Y) with R284K in previously-treated patients failing salvage therapy with tenofovir/emtricitabine. 2012 Retrovirology Conclusion HIV L210W;T215Y;R284K;M41L 5;11;23;0 10;16;28;4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Virological studies reveal that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of nucleoside analogues. 2012 Retrovirology Conclusion HIV R284K 51 56 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. When a mismatched primer terminus or a mispaired dNTP is encountered at the active site, the wild type or Lys66Arg mutant enzymes would efficiently proceed to incorporate these errors, while Ala/Asn/Thr mutants would be inefficient. 2012 The FEBS journal Conclusion HIV K66R 106 114 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Even in the context of high-level resistance, maintaining 3TC pressure prevented reversal M184V in all instances while delaying the emergence of NNRTI resistance. 2012 Viruses Conclusion HIV M184V 90 95 NNRTI 145 150 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. The opposite effect was exerted by ADV; M184V mutant HIV-1 has previously been shown to be hypersusceptible to ADV (as well as its successor, tenofovir). 2012 Viruses Conclusion HIV M184V 40 45 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Using a novel in vitro assay and statistical model, we explored useful strategies of combining antiretroviral drugs with potentially divergent effects on the RT substitution M184V, exerting high-level resistance to 3TC. 2012 Viruses Conclusion HIV M184V 174 179 RT 158 160 23142620 Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases: analysis of flap dynamics and binding mechanism. The primary objective of this study is to understand the interaction mechanisms of SWCNT and wild type (WT) HIV-1-PR as well as a few primary mutants (I50VPR, V82APR and I84VPR). 2012 Journal of molecular graphics & modelling Conclusion HIV I50V;I84V;V82A 151;170;159 157;176;165 PR 114 116 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. In summary, based on available literature and sequence data, the global transmission of K65R and other tenofovir-associated mutations is rare and should not affect tenofovir-based PrEP efficacy at this time. 2012 Journal of the International AIDS Society Conclusion HIV K65R 88 92 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Indeed, recent surveillance reports do indicate that K65R may be increasing in areas where non-B subtypes are predominant. 2012 Journal of the International AIDS Society Conclusion HIV K65R 53 57 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. As previously discussed, although other developed peptide-based fusion inhibitors need many amino acid additions and/or substitutions for the enhancement of their antiviral activity, application of secondary mutations similar to T-20S138A and T-20E137K/S138A is straightforward. 2013 The international journal of biochemistry & cell biology Conclusion HIV S138A 253 258 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. Also of concern is that the patients who developed resistant viruses in the ECHO and THRIVE studies commonly had mutations at both the E138K and M184I positions in the HIV reverse transcriptase gene, leading to dual resistance against both rilpivirine and emtricitabine. 2013 HIV/AIDS (Auckland, N.Z.) Conclusion HIV E138K;M184I 135;145 140;150 RT 172 193 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. The fact that E138K causes cross-resistance among all currently approved members of the non-NRTI family of drugs, including rilpivirine, etravirine, efavirenz, and nevirapine, while M184I confers resistance against both emtricitabine and lamivudine, is also disconcerting. 2013 HIV/AIDS (Auckland, N.Z.) Conclusion HIV E138K;M184I 14;182 19;187 NNRTI 88 96 23413112 Combination therapies, effectiveness, and adherence in patients with HIV infection: clinical utility of a single tablet of emtricitabine, rilpivirine, and tenofovir. This is also a concern because of reports that viruses containing both M184I and E138K may have high replicative fitness. 2013 HIV/AIDS (Auckland, N.Z.) Conclusion HIV E138K;M184I 81;71 86;76 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. H51Y, may simultaneously reduce viral replication and enzymatic activity, while augmenting levels of drug resistance in the presence of a primary resistance mutation. 2013 Retrovirology Conclusion HIV H51Y 0 4 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. R263K, could potentially be advantageous not only for HIV treatment but for strategies aimed at HIV eradication as well. 2013 Retrovirology Conclusion HIV R263K 0 5 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The V86M mutation in HIV-1 CA can confer partial resistance against restriction of HIV-1 replication by mutants of human TRIM5alpha. 2013 Retrovirology Conclusion HIV V86M 4 8 Capsid 27 29 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M abrogates CypA-dependent restriction mechanisms, resulting in an increase of HIV-1 DNA nuclear transport in restrictive conditions. 2013 Retrovirology Conclusion HIV V86M 0 4 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. kcat implies that certain mutations that promote the closed-like conformation (i.e., A71V) could hamper substrate entry resulting in lowered catalytic rate. 2013 Biochemistry Conclusion HIV A71V 85 89 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The recovery of a predominant semi-open population in D30N/M36I/A71V after the step-wise incorporation of these mutations suggests the importance of the semi-open conformation in maintaining turnover rate and catalytic efficiency. 2013 Biochemistry Conclusion HIV A71V;D30N;M36I 64;54;59 68;58;63 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The secondary mutation A71V promotes a closed-like conformation of the protease except when both D30N and M36I mutations are present. 2013 Biochemistry Conclusion HIV A71V;D30N;M36I 23;97;106 27;101;110 PR 71 79 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. This is corroborated by the lack of flap closure upon adding RTV to D30N/M36I/A71V, a construct that exhibited resistance to this inhibitor based on Ki measurements. 2013 Biochemistry Conclusion HIV A71V;D30N;M36I 78;68;73 82;72;77 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Our results showed that I408T, L317W/I408T and V169M/L317W/I408T mutants had the highest impact on MVC susceptibility, mostly due to I408T in V4. 2013 AIDS research and therapy Conclusion HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W 59;53;47;24;37;133;31 64;58;52;29;42;138;36 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Moreover, EFdA would be a good candidate in salvage therapies for patients that fail tenofovir-treatment due to K65R resistance. 2013 Retrovirology Conclusion HIV K65R 112 116 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The primary resistance mutation for EFdA is M184V and combination with tenofovir could be similar to the pair of mutations for 3TC/AZT combination. 2013 Retrovirology Conclusion HIV M184V 44 49 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Therefore, combination of EFdA with tenofovir could help suppress K65R resistance. 2013 Retrovirology Conclusion HIV K65R 66 70 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We have provided virological and biochemical data demonstrating that the K65R RT mutation confers enhanced sensitivity to EFdA. 2013 Retrovirology Conclusion HIV K65R 73 77 RT 78 80 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. In conclusion, our data suggests that the administration of d4T per se is associated with the emergence of both Q151M and K65R MNR mutations which confer resistance to a large range of NRTIs. 2013 PloS one Conclusion HIV K65R;Q151M 122;112 126;117 NRTI 185 190 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. 30fold gain in activity upon addition of the K103N mutation is unclear and makes further crystallographic investigation desirable. 2013 Journal of the American Chemical Society Conclusion HIV K103N 45 50 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. In comparison to etravirine and rilpivirine, the new NNRTIs show similar activity towards the wild-type virus and the K103N/Y181C variant, poorer activity towards the Y181C variant, reduced cytotoxicity, and at least 100-fold greater solubility. 2013 Journal of the American Chemical Society Conclusion HIV K103N;Y181C;Y181C 118;124;167 123;129;172 NNRTI 53 59 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. In comparison to the FDA-approved drug efavirenz, 10b and 10h show improved activity towards the wild-type virus and the K103N/Y181C variant, diminished activity towards the Y181C variant, lower cytotoxicity, and similar solubility. 2013 Journal of the American Chemical Society Conclusion HIV K103N;Y181C;Y181C 121;127;174 126;132;179 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. The contact between Tyr181 and the C6-C7 region of the indolizine appears to be optimal and can explain the significant loss in activity of 10b and 10h towards the Y181C variant. 2013 Journal of the American Chemical Society Conclusion HIV Y181C 164 169 24151856 Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group. The most active compounds are the indolizines 10b and 10h which are strikingly potent with EC50 values of 0.4 nM towards the wild-type virus and 10 nM towards a difficult variant strain bearing K103N and Y181C mutations in the RT enzyme. 2013 Journal of the American Chemical Society Conclusion HIV K103N;Y181C 194;204 199;209 RT 227 229 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Furthermore, protein structure network analyses carried on MD trajectory revealed a long-range allosteric network in RT are also altered upon nevirapine binding or in the presence of connection subdomain mutations N348I/T369I. 2014 Proteins Conclusion HIV N348I;T369I 214;220 219;225 RT 117 119 24174331 Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Hence, all-atom MD simulations of the RT-DNA, RT-DNA-nevirapine, and N348I/T369I mutant RT-DNA-nevirapine complexes were carried out. 2014 Proteins Conclusion HIV N348I;T369I 69;75 74;80 RT;RT;RT 38;46;88 40;48;90 24348205 HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern. In this study, structural properties of two drug resistant PR variants (V82A and D30N/N88D) and the substrates that coevolved with these two variants (AP2VNC-p1 and LP1'Fp1-p6/SP3'Np1-p6, respectively) were investigated in conformational ensembles obtained from MD simulations. 2012 Journal of chemical theory and computation Conclusion HIV D30N;N88D;V82A 81;86;72 85;90;77 Gag;Gag;PR 173;184;59 175;186;61 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The addition of M50I to R263K fails to restore the deficit in HIV replication capacity conferred by R263K. 2014 Retrovirology Conclusion HIV M50I;R263K;R263K 16;24;100 20;29;105 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. This observation is in agreement with the hypothesis that the R263K resistance pathway may represent an evolutionary dead-end for HIV-1; however this hypothesis requires further evaluation and remains to be proven. 2014 Retrovirology Conclusion HIV R263K 62 67 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Several compounds have selectivity indices of greater than 20,000, and certain of these inhibitors have greater antiviral efficacies than RAL against a panel of IN mutants that included Y143R, N155H, G118R, and the double mutants G140S/Q148H and E138K/Q148K. 2014 Journal of medicinal chemistry Conclusion HIV E138K;G118R;G140S;N155H;Q148H;Q148K;Y143R 246;200;230;193;236;252;186 251;205;235;198;241;257;191 IN 161 163 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The S124D mutation, which abrogated RSV IN strand transfer activity, instilled a relatively mild 2-fold defect in sequence non-specific DNA binding. 2014 Nucleic acids research Conclusion HIV S124D 4 9 IN 40 42 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. We accordingly suspect that S119A and S119T mutant enzymes, which retained >50% of strand-transfer activity and showed the greatest variation among integration site sequence preferences, would support normal levels of tDNA binding under similar reaction conditions. 2014 Nucleic acids research Conclusion HIV S119A;S119T 28;38 33;43 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Furthermore, the presence of a high rate of L63P, I93L, V77I and I62V polymorphisms among the Mexican population is similar to that observed in patients that underwent antiretroviral treatments in other American and western European countries. 2014 BMC bioinformatics Conclusion HIV I62V;I93L;L63P;V77I 65;50;44;56 69;54;48;60 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. The D29V mutation increases the probability of resistance to PIs as it generates unstable complexes at the HIV-1 protease active site. 2014 BMC bioinformatics Conclusion HIV D29V 4 8 PR;PI 113;61 121;64 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. However, major mutations including K103N and M184V were identified, indicating that access to virological monitoring is of paramount importance to prevent inappropriate drug switches and preserve efficacy of ART in resource constrained countries. 2014 BMC infectious diseases Conclusion HIV K103N;M184V 35;45 40;50 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. A particularly interesting case is the comparison between R = OEt and CH2OMe in Y181C, where a small change in the substituent results in an entirely different binding mode (Figure 7). 2014 Journal of chemical theory and computation Conclusion HIV Y181C 80 85 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. A typical example of such a lead design effort is the optimization of NNRTIs for the inhibition of HIV-RT and its variant forms (such as the Y181C protein discussed here). 2014 Journal of chemical theory and computation Conclusion HIV Y181C 141 146 NNRTI;RT 70;103 76;105 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. However, some differences have been observed, particularly for Pr in Y181C and OEt in the WT protein, where the ligands' bulky hydrophobic groups are observed to be trapped in energetic wells for the entire simulations using standard sampling techniques. 2014 Journal of chemical theory and computation Conclusion HIV Y181C 69 74 PR 63 65 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. R = ethyl is favored for the WT protein, while the Y181C variant supports more bulky substituents. 2014 Journal of chemical theory and computation Conclusion HIV Y181C 51 56 24895029 Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS. Compound 8c exhibited high anti-HIV potency against wild-type and resistant viral strains with E138 or K101E mutation (EC50 4-7 nM), lower resistance fold change values (RFC: 1.1-2.1) than those of DAPY drug 1b (RFC: 11.8-13) in the same assays. 2014 ChemMedChem Conclusion HIV K101E 103 108 24983495 Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. NMR investigations of L63P clearly demonstrate decreased flexibility of this construct. 2014 FEBS letters Conclusion HIV L63P 22 26 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Overall, these data support a novel model for an l-domain independent function of p6, at least observed for the S40 F mutant, which regulates the association of Gag with the plasma membrane, its K48-linked polyubiquitination, the efficiency in CA-SP1 processing, and thus the infectivity without affecting the release of progeny viruses. 2014 Viruses Conclusion HIV S40F 112 117 SP1;Gag;Gag;Capsid 247;161;82;244 250;164;84;246 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The K65R mutation confers resistance to most NRTIs. 2014 Viruses Conclusion HIV K65R 4 8 NRTI 45 50 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. The K65R mutation reduces both the catalytic efficiency and the mutation rate of HIV-1 RT in vitro and decreases the effect of other NRTI resistance mutations, such as TAMs. 2014 Viruses Conclusion HIV K65R 4 8 NRTI;RT 133;87 137;89 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. X-ray crystallographic studies of K65R mutated HIV-1 RT in complex with template-primer and dNTP or tenofovir has provided critical insights to explain the biochemical properties of K65R RT. 2014 Viruses Conclusion HIV K65R;K65R 34;182 38;186 RT;RT 53;187 55;189 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Conversely, the MD simulation of N43D/S138A double mutant displays a different binding mode between CHR (C34 with S138A mutation) and NHR (with N43D mutation). 2014 PloS one Conclusion HIV N43D;N43D;S138A;S138A 33;144;38;114 37;148;43;119 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In our study, binding affinity of CHR (C34) to NHR with N43D mutation is diminished. 2014 PloS one Conclusion HIV N43D 56 60 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. In this work, we focused on the two mutants of gp41, N43D single mutation and compensatory mutation S138A (yielding N43D/S138A), and delineated detailed characteristics of the interactions and binding model on two mutants. 2014 PloS one Conclusion HIV N43D;N43D;S138A;S138A 53;116;100;121 57;120;105;126 gp41 47 51 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Interestingly, as mentioned above, N43D mutation on NHR affects the membrane fusion mediated by gp41. 2014 PloS one Conclusion HIV N43D 35 39 gp41 96 100 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. It is found that the N43D mutation introduced a negative charge on receptor, thus led to repulsion between receptor and ligand, and induced the conformation changes of complex, and led to greater losses in hydrophobic interactions and hydrogen bond interaction. 2014 PloS one Conclusion HIV N43D 21 25 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Results showed that the N43D mutation is detrimental for inhibitor C34 binding, as many studies mentioned that fusion inhibitors are susceptible to resistance mutations. 2014 PloS one Conclusion HIV N43D 24 28 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. The change of binding mode on N43D/S138A identified here could help to explain why compensatory mutation S138A could partially restores infectivity, lead to increased infectivity and greater resistance to inhibitors than mutation N43D. 2014 PloS one Conclusion HIV N43D;N43D;S138A;S138A 30;230;35;105 34;234;40;110 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. These results may demonstrate once again that neither inhibitor nor HIV-1 itself would escape the impact of N43D single mutation. 2014 PloS one Conclusion HIV N43D 108 112 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. This great hydrophobic interaction of double mutant could partially offset the energy loss arising from N43D. 2014 PloS one Conclusion HIV N43D 104 108 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Importantly, the transmitted T242N escape mutant could be as fit as the wild type virus, suggesting its fitness loss could have been fully repaired by the compensatory amino acids in the donor at the transmission as observed in CH77. 2014 Retrovirology Conclusion HIV T242N 29 34 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Thus, high prevalence of the compensatory amino acids could significantly mitigate the benefits of the fitness costs caused by the T242N escape mutation (Figure 6). 2014 Retrovirology Conclusion HIV T242N 131 136 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. We demonstrated that the fitness loss caused by the T242N mutation could be significantly affected by the differing context of viral backbones because of preexisting compensatory amino acids that either were present in the general viral population (CH40, CH470 and CH58) or selected by immune responses (CH77). 2014 Retrovirology Conclusion HIV T242N 52 57 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. We have elucidated a distinct mechanism of resistance for the H171T IN mutation to the potent ALLINI BI-D. 2014 Retrovirology Conclusion HIV H171T 62 67 IN 68 70 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. It was shown that the N616Q mutation in gp41 resulted in severely decreased gp120 levels in the viral envelopes of HIVNL4.3, HIV-1IIIB and HIV-1HE, afforded markedly decreased CD4-binding by HIV-1NL4.3 and significantly decreased the infectivity of these viral strains. 2014 Retrovirology Conclusion HIV N616Q 22 27 Env;gp120;gp41 102;76;40 111;81;44 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. There are significant co-variation pairs between TDR-associated mutations (V179D/E) and seven overlapping polymorphisms among subtype CRF01_AE. 2014 BMC infectious diseases Conclusion HIV V179D;V179E 75;75 82;82 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. For the double TMC114 bound mutants (V32I-2T and M46L-2T), the resistance is mainly due to the higher entropic contributions. 2015 Journal of molecular graphics & modelling Conclusion HIV M46L;V32I 49;37 53;41 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. For the single bound, the entropy penalty is mainly responsible for the decrease of binding affinity for both the mutant V32I and the mutant M46L. 2015 Journal of molecular graphics & modelling Conclusion HIV M46L;V32I 141;121 145;125 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. It was observed that, the binding free energies are unfavorable for M46L and V32I mutants in their single TMC114 and double TMC114 bound form as compared to WT. 2015 Journal of molecular graphics & modelling Conclusion HIV M46L;V32I 68;77 72;81 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The binding Gibbs free energies for the binding of TMC114 with two mutants V32I and M46L at two sites (2T) are closer to the experimental results than those binding at only active site (1T), which provides a theoretical evidence for the binding of TMC114 with V32I and M46L-HIV-1-pr at both active and flap sites. 2015 Journal of molecular graphics & modelling Conclusion HIV M46L;M46L;V32I;V32I 84;269;75;260 88;273;79;264 PR 280 282 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. The mutants V32I has both direct and indirect effects on the binding affinity, however the mutant M46L elicits primarily indirect towards the resistance. 2015 Journal of molecular graphics & modelling Conclusion HIV M46L;V32I 98;12 102;16 25562662 Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor TMC114: flap dynamics and binding mechanism. We explored the effects of mutations (V32I and M46L) on the binding efficiency of the inhibitor TMC114 in its single bound form to the active site alone and double bound form to the cavity of active site in addition to one of the flap region. 2015 Journal of molecular graphics & modelling Conclusion HIV M46L;V32I 47;38 51;43 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. By contrast, analysis of the RH-IN substrate showed that the interaction between the residue at the P4 and P5 positions and the M36I enzyme was considerably over that of the WT enzyme (Additional file 8). 2014 BMC genomics Conclusion HIV M36I 128 132 IN 32 34 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. In this study we systematically analyzed structural and dynamical features related to the impact of the M36I mutation on the interaction of PR with six of its natural substrates. 2014 BMC genomics Conclusion HIV M36I 104 108 PR 140 142 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Noticeably, however, the presence of the M36I mutation seems to influence the interactions pattern and mobility at the peptide ends. 2014 BMC genomics Conclusion HIV M36I 41 45 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. 10 A away from site I, by introducing the aromatic substitution T215F/Y. 2015 Retrovirology Conclusion HIV T215F;T215Y 64;64 71;71 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Due to its reduced affinity for nucleotides K211I might facilitate the dissociation of the AZT-P4-A, thereby improving the excision reaction in the presence of S345T. 2015 Retrovirology Conclusion HIV K211I;S345T 44;160 49;165 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. In SFVmac RT the substitution E350K improves the catalytic efficiency of dNTP incorporation, thereby compensating the reduced polymerization activity caused by K211I in mt3 and mt4. 2015 Retrovirology Conclusion HIV E350K;K211I 30;160 35;165 RT 10 12 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. K211I increases fidelity by reducing dNTP affinity, thus facilitating dissociation of a non-complementary dNTP. 2015 Retrovirology Conclusion HIV K211I 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Moreover, K211I reduces viral fitness which is at least in part due to the impaired polymerization activity. 2015 Retrovirology Conclusion HIV K211I 10 15 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. S345T is probably the first exchange since it is the only single amino acid exchange conferring moderate AZT resistance. 2015 Retrovirology Conclusion HIV S345T 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. The amino acid exchange S345T can be achieved by a single nucleotide exchange (TCA > ACA). 2015 Retrovirology Conclusion HIV S345T 24 29 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. This, in turn, is compensated by I224T, which improves viral fitness but is not directly involved in the AZT excision process. 2015 Retrovirology Conclusion HIV I224T 33 38 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Thus, S345T is essential for AZT resistance. 2015 Retrovirology Conclusion HIV S345T 6 11 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. At the same time, the primary mutation G118R reduced the integration activity of INA much more significantly than the activity of INB. 2015 Acta naturae Conclusion HIV G118R 39 44 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Recombinant IN activity reduced by drug resistant mutations usually corresponds to a reduced replicative capacity of the mutant virus; therefore, we can expect the emergence and fixation of drug-resistant variants of HIV-1 FSU-A carrying the primary mutation Q148K and compensatory mutations E138K and/or G140S, while the emergence and fixation of drug-resistant variants of FSU-A with the G118R substitution are unlikely. 2015 Acta naturae Conclusion HIV E138K;G118R;G140S;Q148K 292;390;305;259 297;395;310;264 IN 12 14 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. The primary mutation Q148K associated with resistance to RAL and EVG caused a sharp decrease in INA activity, which is partially restored by the secondary mutations E138K and G140S. 2015 Acta naturae Conclusion HIV E138K;G140S;Q148K 165;175;21 170;180;26 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. We can assume that the Ser119Pro substitution, which leads to a more rigid conformation of the INA active site, confers higher enzyme activity but reduces the ability to adapt its active site to the G118R mutation. 2015 Acta naturae Conclusion HIV G118R;S119P 199;23 204;32 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. We have carried out the first systematic study of the enzymatic properties of consensus IN of HIV-1 subtype A strain FSU-A, which is dominant in the territory of the former Soviet Union, containing mutations G118R and Q148K causing HIV-1 resistance to strand transfer inhibitors. 2015 Acta naturae Conclusion HIV G118R;Q148K;G118R;Q148K 209;219;208;218 214;224;213;223 IN 88 90 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Drug combination regimens for AIDS treatment are designed to prevent the emergence or replication of multidrug-resistant HIV-1 strains and our findings of emetine inhibition of NRTIs-resistant virus (M184V) in human primary cells provide additional information on the potential therapeutic use of emetine. 2015 Molecules (Basel, Switzerland) Conclusion HIV M184V 200 205 NRTI 177 182 AIDS 30 34 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. These findings are reassuring, particularly for regions with prevalent HIV-1 with the K65R mutation. 2015 Retrovirology Conclusion HIV K65R 86 90 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. None of the previously reported major mutations (T66AIK, E92Q, Y143RCH, S147G, Q148HRK and N155H) associated with resistance to INIs were observed in HIV-1C Ethiopian isolates, indicating that INIs can be used as a treatment option in Ethiopia and other African countries where HIV-1C is predominately circulating. 2015 Journal of translational medicine Conclusion HIV E92Q;N155H;Q148H;Q148K;Q148R;S147G;T66A;T66I;T66K;Y143C;Y143H;Y143R 57;91;79;79;79;72;49;49;49;63;63;63 61;96;86;86;86;77;55;55;55;70;70;70 IN;IN 128;193 132;197 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. Since this is a non-active site accessory mutation and clinically occurs with other resistant mutants, we have considered two types of mutant proteases double (DBM) V77I-L33F and triple mutant (TPM) V77I-L33F-K20T in the study. 2015 BMC bioinformatics Conclusion HIV K20T;L33F;L33F;V77I;V77I 209;170;204;163;197 213;174;208;169;203 PR 142 151 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. The present study explains the molecular mechanisms through which the V77I mutation in HIV-1 protease cause resistance towards NFV. 2015 BMC bioinformatics Conclusion HIV V77I 70 74 PR 93 101 26700639 Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda. The second-line regimens recommended were appropriate, however, the high rate of the K65R and TAMs is likely to compromise second-line drugs containing other NRTI backbone. 2015 PloS one Conclusion HIV K65R 85 89 NRTI 158 162 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. This double-site binding mode seems to confirm that it could be possible to target both RT-associated functions by a single molecule, retaining full potency of inhibition on drug-resistant mutant RTs such as K103N, Y181C and Y188L. 2016 PloS one Conclusion HIV K103N;Y181C;Y188L 208;215;225 213;220;230 RT;RT 88;196 90;199 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. The presence of primary HIVDR, especially having M184I/V, is associated with detectable HIV RNA at 6 months after ART initiation. 2016 PloS one Conclusion HIV M184I;M184V 49;49 56;56 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Analyses with subtype B RT indicated that K65R and the TAM T215F/Y are not compatible in the absence of the Q151M complex and were rarely found if Q151M or Q151M and at least two additional mutations of the complex were present. 2016 Nucleic acids research Conclusion HIV K65R;Q151M;Q151M;Q151M;T215F;T215Y 42;108;147;156;59;59 46;113;152;161;66;66 RT 24 26 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Moreover, in the presence of the Q151M complex K65R does not lead to AZT sensitivity. 2016 Nucleic acids research Conclusion HIV K65R;Q151M 47;33 51;38 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Obviously, establishment of the M151Q complex is advantageous for the virus during varying treatment regimens with changing NRTIs, since it is efficient against multiple NRTIs. 2016 Nucleic acids research Conclusion HIV M151Q 32 37 NRTI;NRTI 124;170 129;175 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. the HIV Drug Resistance Database (http://hivdb.stanford.edu/), which give high AZT resistance mutation scores for Q151M occurring in coexistence with the TAMs T215F and M41L. 2016 Nucleic acids research Conclusion HIV M41L;Q151M;T215F 169;114;159 173;119;164 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Thus, a strong functional antagonism of K65R and T215F/Y in the presence of two or more additional TAMs may exist. 2016 Nucleic acids research Conclusion HIV K65R;T215F;T215Y 40;49;49 44;56;56 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. We show here, that subtype AG MR-RT which harbors K65R, T215F and three additional TAMs concomitantly is still functional as a polymerase and RNase H. 2016 Nucleic acids research Conclusion HIV K65R;T215F 50;56 54;61 Pol;RT 127;33 137;35 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Nevertheless, capsid stiffness is not strictly correlated with infectivity, as shown by the phenotype of the E45A/R132T double mutant. 2016 Retrovirology Conclusion HIV E45A;R132T 109;114 113;119 Capsid 14 20 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Current SAR study further revealed that (1) a carbonyl group in the R1 substituent conjugated with the central phenyl ring (B-ring) is necessary to combat drug resistance from the E138K mutant, (2) hetero atoms (O, N, or Br) in the R1 substituent favor improved druglike ADME properties, (3) bulky R1 groups should be avoided, and (4) Br and OMe could replace the two original methyl groups in DAANs, but two methoxy groups (X) on the C-ring led to reduced potency, because a steric effect altered the favorable conformation of the C-ring. 2016 Journal of medicinal chemistry Conclusion HIV E138K 180 185 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Current structural modification studies of DAANs showed that optimization of the R1 and X substituent on the central phenyl ring (B-ring) and phenoxy ring (C-ring), respectively, could enhance, or maintain, high potency against wild-type and E138K mutant HIV-1 replication and improve molecular aqueous solubility, lipophilicity, and metabolic stability, thus reaching a good balance between high antiviral potency and multiple druglike properties. 2016 Journal of medicinal chemistry Conclusion HIV E138K 242 247 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. For instance, compounds 6a, 6b, 14c, and 14d exhibited high potency against the wild type as well as E138K mutant (low nanomolar EC50 values) with low resistance FC values of 1.9-2.2, which are much lower than that of 1b (FC = 10). 2016 Journal of medicinal chemistry Conclusion HIV E138K 101 106 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. Most interestingly, we found that the introduced R1 side chain provided a possibility for overcoming the new drug resistance from E138K, a major HIV-1 viral mutant with resistance to the NNRTI drug 1b. 2016 Journal of medicinal chemistry Conclusion HIV E138K 130 135 NNRTI 187 192 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. The modeling study with representative compounds 6a and 14d provided a rationale supporting the role of an optimized R1 group promoting greater efficacy against the E138K mutant, as well as demonstrating possible modification space between subdomains p66 and p51. 2016 Journal of medicinal chemistry Conclusion HIV E138K 165 170 27070547 Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor Agents: Optimization of Diarylanilines with High Potency against Wild-Type and Rilpivirine-Resistant E138K Mutant Virus. The structural design of these compounds was aimed at overcoming the E138K drug-resistant variants, and the current results should help in the development of new NNRTI candidates that can overcome the major drug resistance conferred to the new-generation HIV-1 NNRTI drug 1b, as well as other RT-mutated drug resistances. 2016 Journal of medicinal chemistry Conclusion HIV E138K 69 74 NNRTI;NNRTI;RT 162;261;293 167;266;295 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. In summary, despite the limitations of our study, which is just a pilot study that should be confirmed in further studies, we have shown the proof of concept that for patients who failed a Raltegravir containing regimen in the past, who are currently virologically suppressed, and lack the resistance information at failure, studying Integrase resistance in the proviral DNA accurately reflects the possibility of properly identifying N155H and some secondary mutations 29-53 months after failure. 2016 BMC infectious diseases Conclusion HIV N155H 435 440 IN 334 343 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. High prevalence of resistance, in particular K65R, was observed, impacting future treatment options. 2016 Journal of the International AIDS Society Conclusion HIV K65R 45 49 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Moreover, though currently low, the impact of K65R transmission in such settings on first-line regimens, as well as on pre-exposure prophylaxis (PrEP) with TDF-containing regimens, is yet to be determined. 2016 Journal of the International AIDS Society Conclusion HIV K65R 46 50 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. In the D30N complex, the binding affinity of residue 30 increases but that of residues 28 and 29 decrease. 2016 International journal of molecular sciences Conclusion HIV D30N 7 11 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. Residue 54 in the I54M complex shows two alternate conformations. 2016 International journal of molecular sciences Conclusion HIV I54M 18 22 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The entropic contribution also plays an important role in the I50V complex. 2016 International journal of molecular sciences Conclusion HIV I50V 62 66 27240358 Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor. The I50V mutation changes the binding package. 2016 International journal of molecular sciences Conclusion HIV I50V 4 8 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. We have also identified the impact of the I37K and N126K mutations on epitopes in both gp120 and gp41. 2016 Retrovirology Conclusion HIV I37K;N126K 42;51 46;56 gp120;gp41 87;97 92;101 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. At least two of the three clinically relevant drug resistant integrase mutants we tested, N155H and G140S/Q148H, which reduce the enzymatic activity of integrase, caused aberrant integrations, even in the absence of any added drug. 2016 Retrovirology Conclusion HIV G140S;N155H;Q148H 100;90;106 105;95;111 IN;IN 61;152 70;161 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In contrast, a locally fluctuating structure including conformational exchange was observed only for E12A for the alpha1-2 loop and helix 5 regions. 2016 PloS one Conclusion HIV E12A 101 105 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. More flexible structures were observed through the entire molecule in WT than in E12A. 2016 PloS one Conclusion HIV E12A 81 85 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. The pervading resistance to PZA found to be associated with these two genotypes can be explained by their strong association with G145A and A403C pncA mutations, respectively. 2016 The American journal of tropical medicine and hygiene Conclusion HIV A403C;G145A 140;130 145;135 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Except for V82S at the active site and flap mutation G48V, all other mutations are distal to the active site, yet PRS17 exhibits poor binding affinity for clinical PIs and synergistic changes that alter the conformation and dynamics of the flaps. 2016 PloS one Conclusion HIV G48V;V82S 53;11 57;15 PI;PR 164;114 167;116 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. In contrast to other highly resistant proteases like PR20, PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with DRV resistance, although it exhibits 10,000-fold weaker binding affinity for DRV relative to the wild type PR. 2016 PloS one Conclusion HIV I47V;I50V;I54L;I54M;I84V;L76V 98;104;110;110;126;117 102;108;115;115;130;121 PR;PR;PR;PR 38;53;59;255 47;55;61;257 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. As expected in Africa, the predominant NRTI mutation observed was M184V. 2016 BMC research notes Conclusion HIV M184V 66 71 NRTI 39 43 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The M184V and K65R DRMs might be due to the Tenofovir and Lamivudine ART backbone and the triple nucleoside regimen of Abacavir-Zidovudine-Lamivudine that most of our patients were initiated on. 2016 BMC research notes Conclusion HIV K65R;M184V 14;4 18;9 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The NNRTI mutations observed included K103N, G190A and Y181C which cause high level resistance to Nevirapine and variable resistance to Efavirenz. 2016 BMC research notes Conclusion HIV G190A;K103N;Y181C 45;38;55 50;43;60 NNRTI 4 9 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. The observed PI resistance mutations (V82A, V82F, V82S, M46I, M46L and I54V) are clinically significant because they are associated with highest levels of phenotypic resistance and/or strongest evidence for interfering with successful PI therapy. 2016 BMC research notes Conclusion HIV I54V;M46I;M46L;V82A;V82F;V82S 71;56;62;38;44;50 75;60;66;42;48;54 PI;PI 13;235 15;237 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. Type 1 TAM M41L causes higher levels of phenotypic and clinical resistance to thymidine analogues and cross resistance to Abacavir, Tenofovir and Didanosine than Type 11 K70R. 2016 BMC research notes Conclusion HIV M41L 11 15 28195728 Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K. Drug resistant mutations V32I, I47V and V82I do not seem to alter the hydrogen bonding pattern and hydrophobic interactions of amprenavir with the enzyme, even though the 100K X-ray crystal structure of PRTM-APV suggests otherwise. 2017 Journal of medicinal chemistry Conclusion HIV I47V;V32I;V82I 31;25;40 35;29;44 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. More importantly, pre-treatment detection of T97A did not increase the risk of virologic failure on EVG or RAL-based therapies. 2017 PloS one Conclusion HIV T97A 45 49 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The T97A integrase mutation, infrequently associated with emergent EVG and RAL resistance at virologic failure, was identified as a low frequency naturally occurring integrase polymorphism of greater prevalence in HIV-1 non-B than B subtypes. 2017 PloS one Conclusion HIV T97A 4 8 IN;IN 9;166 18;175 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. While T97A may confer low-level reductions in INSTI susceptibility in the context of other integrase polymorphisms, mutational pathways of INSTI resistance at virologic failure were not driven by the persistence of T97A. 2017 PloS one Conclusion HIV T97A;T97A 6;215 10;219 IN;INSTI;INSTI 91;46;139 100;51;144 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. The predicted resulting amino acid sequence led to an amino acid change at position 77, from arginine to glutamine (R77Q), and at position 3 from glutamine to arginine (Q3R). 2014 JMM case reports Conclusion HIV Q3R;Q3R;R77Q 169;139;116 172;167;120 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. The vpr gene of the parents revealed a predicted change at position 77, but the codons indicated a change from arginine to histidine (R77H). 2014 JMM case reports Conclusion HIV R77H 134 138 Vpr 4 7 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Because no conventional or cryptic T cell responses were detected for the regions containing the K43R mutation and that the Gag protein does not elicit neutralizing antibodies, the strong selection pressure on the K43R mutation could not be from adaptive T and B cell responses. 2017 Retrovirology Conclusion HIV K43R;K43R 97;214 101;218 Gag 124 127 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. However, the significant fitness loss of the K43R reversion mutation indicates that it was not simply reverted back to the consensus state due to the lack of allele-specific selection pressure, but instead it was strongly selected in vivo. 2017 Retrovirology Conclusion HIV K43R 45 49 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. It will be important to determine if the K43R mutation or similar mutations are selected by NK cell responses and anti-Gag antibody responses or by T cell responses targeting to the spliced epitopes. 2017 Retrovirology Conclusion HIV K43R 41 45 Gag 119 122 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. K43R should not be a compensatory mutation for any mutations in LTR because such mutations were not detected in the viral genome. 2017 Retrovirology Conclusion HIV K43R 0 4 LTR 64 67 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Mutations in vpu, env and nef were also detected in the 3'-half genome sequences when the K43R mutation was detected. 2017 Retrovirology Conclusion HIV K43R 90 94 Nef;Vpu;Env 26;13;18 29;16;21 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Since the K43R mutation was found in the WF9 epitope restricted by the B*35 allele that CH0131 did not carry, it was mostly likely a reversion mutation (to the consensus of subtype C viruses). 2017 Retrovirology Conclusion HIV K43R 10 14 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The K43R mutation quickly emerged and was rapidly fixed in the viral population after infection in CH0131, suggesting that it was strongly selected in the host. 2017 Retrovirology Conclusion HIV K43R 4 8 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The majority of the N323tc mutation was found in the sequences that had the K43R and N242T mutations. 2017 Retrovirology Conclusion HIV K43R;N242T 76;85 80;90 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The other possibility is that K43R is a compensatory mutation. 2017 Retrovirology Conclusion HIV K43R 30 34 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Therefore, if there were T cell responses targeting the K43R site that were undetectable (and far from immunodominant), it would be difficult to envision how it could exert any significant pressure to select such a rapid escape, with a fitness loss. 2017 Retrovirology Conclusion HIV K43R 56 60 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. This is also not likely since the K43R mutation was the very first mutation that selected and fixed in the viral population before other mutations were detected in the 5'-half genome. 2017 Retrovirology Conclusion HIV K43R 34 38 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Thus, it is unlikely that the K43R mutation was selected by NK cell responses and anti-Gag antibody responses. 2017 Retrovirology Conclusion HIV K43R 30 34 Gag 87 90 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Thus, the N323tc mutation was not likely selected by the host, but was instead a concurrent mutation together with the N242T or K43R mutation. 2017 Retrovirology Conclusion HIV K43R;N242T 128;119 132;124 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. We have previously found that three other reversion mutations (V247I and T242N in Gag as well as I64T in Tat) also did not cause detectable fitness differences. 2017 Retrovirology Conclusion HIV I64T;T242N;V247I 97;73;63 101;78;69 Tat;Gag 105;82 108;85 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. While only the K43R mutation was fully documented here, we found other possible examples of selected escapes that were not within an epitope stimulating a measurable T cell response in our previous studies. 2017 Retrovirology Conclusion HIV K43R 15 19 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. This study identified differences in the mutational response of RT to NRTI treatment between subtype B and South African subtype C, with novel mutation E529D, in particular, strongly associated with treatment experience. 2017 Viruses Conclusion HIV E529D 152 157 NRTI;RT 70;64 74;66 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. In general, a series of novel diarylnicotinamide triazole analogues were rationally designed based on structure-guided approach, synthesized and evaluated for their bioactivities against HIV-1 (IIIB, K103 N + Y181C, L100I, K103 N, E138K, Y181C, Y188L and F227L + V106A) and HIV-2 (ROD) in MT-4 cells. 2018 European journal of medicinal chemistry Conclusion HIV E138K;F227L;K103N;K103N;L100I;V106A;Y181C;Y181C;Y188L 231;255;200;223;216;263;209;238;245 236;260;206;229;221;268;214;243;250 29635166 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus. Noteworthily, regarding the inhibitory activity against E138K, the major drug resistant mutant to the new generation HIV-1 NNRTIs, 3b8 and 3b9 with triazole linker targeting the entrance channel of NNRTIs in RT are equally potent to marketed drug ETR but with much lower cytotoxicity. 2018 European journal of medicinal chemistry Conclusion HIV E138K 56 61 NNRTI;NNRTI;RT 123;198;208 129;204;210 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. In addition, our results suggested an atomic mechanism that corresponded to cooperation between substitutions I32V and L76M, yielding the large structural changes at residue 45 in PR2 relative to PR1. 2018 Scientific reports Conclusion HIV I32V;L76M 110;119 114;123 PR;PR 180;196 183;199 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Structural analyses of PR1 and PR2 pockets suggest their amino acid changes (T31S, V32I, M46I, I47V, L76M and V82I) induce structural changes in their substituted and non-substituted residues that modify the physicochemical properties of PR2 pockets. 2018 Scientific reports Conclusion HIV I47V;L76M;M46I;T31S;V32I;V82I 95;101;89;77;83;110 99;105;93;81;87;114 PR;PR;PR 31;238;23 34;241;26 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Our data confirm that modern ART and laboratory monitoring have greatly reduced the occurrence of multi-NRTI resistance due to T69i and Q151M in the UK, a change that is very likely to have also occurred in other developed countries. 2018 AIDS research and therapy Conclusion HIV Q151M 136 141 NRTI 104 108 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. In particular, viruses carrying resistance mutations with low fitness cost are spread continuously by onwards transmission, and German MSM are generally driving the spread in Germany, both within transmission networks and outside of networks as shown for the K103N mutation. 2018 PloS one Conclusion HIV K103N 259 264 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. A repeat INSTI genotype noted T97A (Supplementary Tables 2 and 3). 2018 Open forum infectious diseases Conclusion HIV T97A 30 34 INSTI 9 14 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. In November 2014, a PhenoSense Integrase GT assay detected DRMs to NRTI, NNRTI, PI, and the INSTI-associated mutations E138T, G140S, and Q148H. 2018 Open forum infectious diseases Conclusion HIV E138T;G140S;Q148H 119;126;137 124;131;142 IN;INSTI;NNRTI;NRTI;PI 31;92;73;67;80 40;97;78;71;82 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Interpretation of cumulative genotypic information (Standford/ANRS algorithms) indicated high-level resistance to all US Food and Drug Administration (FDA)-approved nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, except for intermediate resistance to DTG with the G140S and Q148H mutations (Supplementary Table 3). 2018 Open forum infectious diseases Conclusion HIV G140S;Q148H 366;376 371;381 NNRTI;NRTI;PR;INSTI;NNRTI;NRTI;PI 218;165;276;307;267;210;297 254;197;284;313;273;215;300 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. NGS detected T97A in addition to the previously detected integrase mutations (Supplementary Table 2). 2018 Open forum infectious diseases Conclusion HIV T97A 13 17 IN 57 66 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Retrospective NGS analysis of a plasma sample from November 2015 (while the individual was on RAL) did not reveal the T97A mutation. 2018 Open forum infectious diseases Conclusion HIV T97A 118 122 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. T97A was not detected by Sanger sequencing or by next-generation sequencing (NGS; Illumina), which has a sensitivity of c. 2018 Open forum infectious diseases Conclusion HIV T97A 0 4 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Thus T97A emerged within 8 weeks of consistent DTG therapy. 2018 Open forum infectious diseases Conclusion HIV T97A 5 9 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. Especially, 13c2 and 13c4 proved to be the exceptionally potent inhibitors, exhibiting EC50 values of 0.9-7.0 nM against single NNRTI-resistant strains L100I, K103N, Y181C, Y188L, and E138K in MT-4 cells and bringing approximately 1.3- to 3.6 fold improvement in potency compared with ETV (EC50 = 3.3-20.4 nM). 2019 Journal of medicinal chemistry Conclusion HIV E138K;K103N;L100I;Y181C;Y188L 184;159;152;166;173 189;164;157;171;178 NNRTI 128 133 30624934 Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties. For double mutant HIV-1 strains F227L+V106A and RES056, both inhibitors displayed comparable activities with those of ETV. 2019 Journal of medicinal chemistry Conclusion HIV F227L;V106A 32;38 37;43 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. At that time, resistance testing showed NRTI (M184V, T69D, T215S, D67N, K219Q), NNRTI (Y181C, Y188L, H221Y) and PI (L10I, D30N, K20T, L33F, K43T, N88D) resistance, with PI resistance to nelfinavir. 2019 Open forum infectious diseases Conclusion HIV D30N;D67N;H221Y;K20T;K219Q;K43T;L10I;L33F;M184V;N88D;T215S;T69D;Y181C;Y188L 122;66;101;128;72;140;116;134;46;146;59;53;87;94 126;70;106;132;77;144;120;138;51;150;64;57;92;99 NNRTI;NRTI;PI;PI 80;40;112;169 85;44;114;171 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. Follow-up NGS sequencing 3 months after the first resistance test showed the R263K mutation at <5% in a sample with a VL of 61 000 copies/mL. 2019 Open forum infectious diseases Conclusion HIV R263K 77 82 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. Poor engagement continued for 18 months; at this later, time integrase resistance testing showed the R263K mutation conferring low-level resistance to DTG and raltegravir, with intermediate resistance to elvitegravir. 2019 Open forum infectious diseases Conclusion HIV R263K 101 106 IN 61 70 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. R263K was confirmed by next-generation sequencing (NGS) using an analysis percentage minority variant threshold of >20%. 2019 Open forum infectious diseases Conclusion HIV R263K 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. The VL dropped to 700 copies/mL; however, it rebounded to 6000 copies/mL: at that time, a first resistance test showed M184V and D30N mutations. 2019 Open forum infectious diseases Conclusion HIV D30N;M184V 129;119 133;124 30788976 Synthesis and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors. A new series of trisubstituted DAPY analogues was prepared starting from commercially available trisubstituted pyrimidines and evaluated for their anti-HIV potency against wild type and two clinically relevant mutant strains (K103N and Y181C). 2019 Antiviral chemistry & chemotherapy Conclusion HIV K103N;Y181C 226;236 232;241 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. A repeat genotype performed at this time showed the M184I mutation, conferring resistance to lamivudine and emtricitabine, and probable resistance to raltegravir, predicted resistance to elvitegravir but no predicted dolutegravir resistance. 2019 Journal of the International Association of Providers of AIDS Care Conclusion HIV M184I 52 57 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. The genotype at this time demonstrated no reverse transcriptase (RT) gene mutations, but the following protease gene mutations: L10V, M36I, L63P, H69H/Y, A71T/A, and I93L. 2019 Journal of the International Association of Providers of AIDS Care Conclusion HIV A71A;A71T;H69H;H69Y;I93L;L10V;L63P;M36I 154;154;146;146;166;128;140;134 160;160;152;152;170;132;144;138 RT;PR;RT 42;103;65 63;111;67 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. The genotype performed at this time showed the following protease inhibitor gene mutations: I13I/V, E35D, D60E, L63P, I64V, and V77I and RT mutation V106I/V/M conferring resistance to efavirenz and nevirapine. 2019 Journal of the International Association of Providers of AIDS Care Conclusion HIV D60E;E35D;I13I;I13V;I64V;L63P;V106I;V106M;V106V;V77I 106;100;92;92;118;112;149;149;149;128 110;104;98;98;122;116;158;158;158;132 PR;RT 57;137 65;139 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. The genotype report at that time showed protease gene mutations L63P and V77I, and the patient had prior exposure to zidovudine, lamivudine, didanosine, and nevirapine, since her diagnosis in 2004. 2019 Journal of the International Association of Providers of AIDS Care Conclusion HIV L63P;V77I 64;73 68;77 PR 40 48 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. The HIV genotype at this time reported the RT gene mutations M184V and L100L/F, conferring resistance to emtricitabine and lamivudine, and protease gene mutations L10V, M36I/M, K43R, L63P, H69Y, A71A/V, and I93L. 2019 Journal of the International Association of Providers of AIDS Care Conclusion HIV A71A;A71V;H69Y;I93L;K43R;L100F;L100L;L10V;L63P;M184V;M36I;M36M 195;195;189;207;177;71;71;163;183;61;169;169 201;201;193;211;181;78;78;167;187;66;175;175 PR;RT 139;43 147;45 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Apparently, all these changes could be attributed to the E11D, K14R, S24N, and M50I amino acid substitutions residing in the N-terminal domain of IN_CRF, which plays an important role in IN multimerization and binding to viral DNA. 2019 Acta naturae Conclusion HIV E11D;K14R;M50I;S24N 57;63;79;69 61;67;83;73 IN 187 189 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The G118R/E138K mutations resulted in only a seven-fold increase of the resistance of IN_CRF to raltegravir. 2019 Acta naturae Conclusion HIV E138K;G118R 10;4 15;9 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. The results obtained allowed us to suggest that the resistance of the HIV-1 genetic variant CRF63_02A1 to raltegravir may develop primarily due to the emergence and fixation of Q148K/G140S mutations as it was described for other HIV-1 subtypes. 2019 Acta naturae Conclusion HIV G140S;Q148K;G140S;Q148K 184;178;183;177 189;183;188;182 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Finally, examination of the alterations in dihedral angles within the protease using the Jensen-Shannon divergence suggests that alterations in hydrophobic sliding due to the L89V and L90M mutations may modulate the fluctuations at the flap tips. 2019 Biochemistry Conclusion HIV L89V;L90M 175;184 179;188 PR 70 78 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In all other combinations, that is when only L89V is present, neither or both mutations are present, the changes to the structure of the protease are more localized and do not include a stable expanded state of the catalytic site. 2019 Biochemistry Conclusion HIV L89V 45 49 PR 137 145 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In particular, in the absence of L89V, the L90M mutation causes changes throughout the structure of the DRV-resistant KY variant that encompass secondary structure elements both near and distal to the site of mutation, including an expansion of the catalytic site. 2019 Biochemistry Conclusion HIV L89V;L90M 33;43 37;47 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In the KY background, the L90M mutation led to a less tightly bound DRV that exhibited increased fluctuations, particularly at the P2' moiety. 2019 Biochemistry Conclusion HIV L90M 26 30 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. In the sequence backgrounds of both the highly resistant variant and the wild-type protease, the L90M mutation led to increased fluctuations of the flaps, an observation that suggests a loss of affinity for DRV, while the addition of the L89V mutation attenuated this increase in fluctuations. 2019 Biochemistry Conclusion HIV L89V;L90M 238;97 242;101 PR 83 91 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. These changes in fluctuations are due to an increased sampling of DRV dihedral angles, with the presence of L90M being associated with the broadest sampling of angles at the P2' moiety. 2019 Biochemistry Conclusion HIV L90M 108 112 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. These measurements indicate that the L90M mutation provides resistance to inhibition by DRV, but at the expense of a dramatic loss in enzymatic efficiency. 2019 Biochemistry Conclusion HIV L90M 37 41 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. This "rescue" effect of the L89V mutation for L90M were recapitulated in the widely-studied NL4-3 wild-type protease. 2019 Biochemistry Conclusion HIV L89V;L90M 28;46 32;50 PR 108 116 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. This expansion of the catalytic site and concomitant conformational sampling of the inhibitor lead to a loss of water-mediated hydrogen bonding between residue I50 and the sulfonamide oxygen of DRV when L90M is present without L89V in the KY sequence background. 2019 Biochemistry Conclusion HIV L89V;L90M 227;203 231;207 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. Using as a test-bed an HIV-1 protease variant that is highly resistant to DRV inhibition (here called "KY"), measurements of Ki, KM and kcat were carried out on variants that had either L89V or L90M present, along with both or neither of these mutations. 2019 Biochemistry Conclusion HIV L89V;L90M 186;194 190;198 PR 29 37 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. We have presented a detailed analysis of the interdependence between the L89V and L90M drug resistance mutations in HIV-1 protease. 2019 Biochemistry Conclusion HIV L89V;L90M 73;82 77;86 PR 122 130 31386353 Molecular Determinants of Epistasis in HIV-1 Protease: Elucidating the Interdependence of L89V and L90M Mutations in Resistance. When combined with the L89V mutation, however, enzymatic efficiency is partly restored while maintaining much of the resistance to inhibition imparted by the L90M mutation. 2019 Biochemistry Conclusion HIV L89V;L90M 23;158 27;162 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The mutant (E35D G S) showed decreased affinity for the substrate. 2019 Journal of enzyme inhibition and medicinal chemistry Conclusion HIV E35D 12 17 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S119R could have a substantial impact on how the IN binds to the tDNA, as well as G118R. 2019 Frontiers in microbiology Conclusion HIV G118R;S119R 82;0 87;5 IN 49 51 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The clustering of the co-occurrence network showed that mutation E138K is possibly involved in maintaining DNA-recognition function when other DNA-anchoring lysine residues are mutated. 2019 Frontiers in microbiology Conclusion HIV E138K 65 70 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. The co-occurrence network showed that N155H and Q148HR pathways share more co-occurring mutations with each other than with Y143R, which is consistent with the frequency by which N155H is further converted into Q148HR or Y143CRH. 2019 Frontiers in microbiology Conclusion HIV N155H;N155H;Q148H;Q148H;Q148R;Q148R;Y143C;Y143H;Y143R;Y143R 38;179;48;211;48;211;221;221;221;124 43;184;54;217;54;217;228;228;228;129 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. Reformation of the closed stated was observed with F99Y when no instances of reformation of the closed state were seen with WT. 2019 The journal of physical chemistry. B Conclusion HIV F99Y 51 55 31640343 Energetics of Flap Opening in HIV-1 Protease: String Method Calculations. To show the relationship between flap opening and hydrophobic distal pocket closing, the C-terminal residue of each monomer at position 99 was mutated F99Y. 2019 The journal of physical chemistry. B Conclusion HIV F99Y 151 155 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577R disrupts two hydrogen bonds between PIE12-trimer and the inhibitor-binding pocket and substantially decreases binding affinity. 2019 Retrovirology Conclusion HIV Q577R 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The primary resistance mutation, Q577R/N/K, is found in the conserved PIE12-trimer binding pocket on the gp41 N-trimer. 2019 Retrovirology Conclusion HIV Q577K;Q577N;Q577R 33;33;33 42;42;42 gp41 105 109 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The R841I mutation identified in this segment may be considered as specific genetic signature, as well as its phenotypic properties during HIV-1 transmission merits further study. 2019 Viruses Conclusion HIV R841I 4 9 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Finally, given that we did not find benefit of 3TC in patients failing first-line treatment, a prospective clinical trial could determine whether there is benefit for including XTC in second-line regimens for the treatment of persons whose viruses develop M184I/V after VF on a first-line treatment regimen. 2020 The Journal of infectious diseases Conclusion HIV M184I;M184V 256;256 263;263 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. In summary, we show that 3TC-resistant and 3TC-susceptible viruses show similar VLs in patients failing NNRTI-based ART containing 3TC, tenofovir, and NNRTI, likely in part due to viral evolution of compensatory changes that maintain replication efficiency of M184V/I-containing viruses. 2020 The Journal of infectious diseases Conclusion HIV M184I;M184V 260;260 267;267 NNRTI;NNRTI 104;151 109;156 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. HIV-1 selects E560K mutation to increase thermostability of the 6HB and is further resistant to N peptide inhibitors, and selects E560G or E560D as compensatory mutations to destabilize the 6HB to reduce inhibitor binding and to be resistant to T20. 2019 Retrovirology Conclusion HIV E560D;E560G;E560K 139;130;14 144;135;19 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Especially 10i was superior to both NVP and EFV against the HIV-1RT-L100I/K103N, which suggested that it has the potential for use in developing a new NNRTI. 2020 European journal of medicinal chemistry Conclusion HIV K103N;L100I 74;68 79;73 NNRTI 151 156 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Moreover, the two candidates strongly suppressed NNRTI-resistant HIV-1 carrying the RT-K103N/Y181C mutation. 2020 European journal of medicinal chemistry Conclusion HIV K103N;Y181C 87;93 92;98 NNRTI;RT 49;84 54;86 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. We found a high frequency of the polymorphic combination L101I/T124A than that reported for subtype B strains. 2020 AIDS research and therapy Conclusion HIV L101I;T124A 57;63 62;68 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. We deciphered the role of the S68G mutation in the HIV RT of CRF01_AE strains. 2020 BMC infectious diseases Conclusion HIV S68G 30 34 RT 55 57 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Our structures also explain a common mechanism for 3TC/ETV resistance by severe steric clash between the M184V/I (M204V/I in HBV) side-chain and the oxathiolane/methylene of bound 3TC-TP/ETV-TP. 2020 Scientific reports Conclusion HIV M184I;M184V 105;105 112;112 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. The structure of HIV-1 RT3MB/F160M/M184V:DNA in complex with 3TC-TP also showed that bound 3TC-TP deviated from the tight binding position observed in RT3MB with disordered triphosphate moiety, indicating a steric clash evasion with Val184 Cgamma1. 2020 Scientific reports Conclusion HIV F160M;M184V 29;35 34;40 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. These structures together with a previous RTQ151M in complex with ETV-TP revealed that 1) 3TC-TP binds in an atypical binding conformation dissimilar to those of common d-isomer NRTIs/dNTPs and 2) both oxathiolane of 3TC-TP and cyclopentyl methylene of ETV-TP bind through directly pushing back the Met184 side-chain. 2020 Scientific reports Conclusion HIV Q151M 44 49 NRTI;RT 178;42 183;44 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. We generated a 3TC/ETV-sensitive HIV-1 variant with HBV-associated mutations 3MB (F115Y/Y116F/Q151M) in RT, and successfully simulated 3TC/ETV resistance in HBV using HIV3MB with mutations F160M/M184V. 2020 Scientific reports Conclusion HIV F115Y;Q151M;Y116F;F160M;M184V 81;94;88;189;195 87;99;93;194;200 RT 104 106 32111013 Design of Biphenyl-Substituted Diarylpyrimidines with a Cyanomethyl Linker as HIV-1 NNRTIs via a Molecular Hybridization Strategy. The best compound 10p exhibited EC50 values of 0.027, 0.17, 0.87, 0.90, and 1.21 microM against the WT, E138K, Y181C, K103N, and L100I variants, respectively. 2020 Molecules (Basel, Switzerland) Conclusion HIV E138K;K103N;L100I;Y181C 104;118;129;111 109;123;134;116 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. SDRMs (D67N and D67E) belonging to the NRTIs class were found in two subjects and SDRMs) K103N and V106A (belonging to the NNRTIs class were found in three subjects. 2020 PloS one Conclusion HIV D67E;D67N;K103N;V106A 16;7;87;99 20;12;94;104 NNRTI;NRTI 123;39 129;44 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Based on the alignment of env of MK1 and #818, we selected 11 substitutions: N133S, S147G (V1 region), N169D, K187E, S190N (V2 region), N237T, D282N, S294F (C2 region), A389T (V4 region), T437A (C4 region), and T463P (V5 region). 2020 Pathogens (Basel, Switzerland) Conclusion HIV A389T;D282N;K187E;N133S;N169D;N237T;S147G;S190N;S294F;T437A;T463P 169;143;110;77;103;136;84;117;150;188;211 174;148;115;82;108;141;89;122;155;193;216 Env 26 29 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. However, higher neutralisation resistance was conferred by the N169D and K187E substitutions, which added negative charges, and the S190N (V2 region of gp120) and A389T (V4 region) substitutions, which created sites for N-glycan. 2020 Pathogens (Basel, Switzerland) Conclusion HIV A389T;K187E;N169D;S190N 163;73;63;132 168;78;68;137 gp120 152 157 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. The combinations N169D+K187E, N169D+S190N, and N169D+A389T led to MK1 having similar neutralisation resistance to #818, while the combination N169D +S190N+ A389T led to identical neutralisation resistance between MK1 and #818. 2020 Pathogens (Basel, Switzerland) Conclusion HIV A389T;A389T;K187E;N169D;N169D;N169D;N169D;S190N;S190N 53;156;23;17;30;47;142;36;149 58;161;28;22;35;52;147;41;154 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. The neutralisation resistance of the mutant MK1s that harboured 7 of the 11 substitutions (N133S, S147G, N237T, D282N, S294F, T437A, and T463P) did not change significantly. 2020 Pathogens (Basel, Switzerland) Conclusion HIV D282N;N133S;N237T;S147G;S294F;T437A;T463P 112;91;105;98;119;126;137 117;96;110;103;124;131;142 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. Therefore, N169D of V2 region is a key substitution for acquiring neutralisation resistance against anti-V3 antibodies. 2020 Pathogens (Basel, Switzerland) Conclusion HIV N169D 11 16 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Specifically, the E45A/R132T mutant virus suggests that disrupted interactions with cellular factors, rather than capsid stability, is responsible for the delayed uncoating kinetics seen in E45A mutant virus. 2020 Virology journal Conclusion HIV E45A;E45A;R132T 18;190;23 22;194;28 Capsid 114 120 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The CA mutations N74D and E45A delayed HIV uncoating, while the compensatory mutation R132T was able to rescue the uncoating kinetics of E45A mutant virus despite still having a hyperstable capsid. 2020 Virology journal Conclusion HIV E45A;E45A;N74D;R132T 26;137;17;86 30;141;21;91 Capsid;Capsid 190;4 196;6 32180823 Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Common NNRTI-resistance through K103N seems innocuous to the efficacy of DOR-based regimens, whereas, in treatment-naive individuals, resistance to DOR can occur most commonly through the development of substitutions at position V106. 2020 Drugs in context Conclusion HIV K103N 32 37 NNRTI 7 12 32264923 Multidrug-resistant HIV viral rebound during early syphilis: a case report. A genotype resistance test (GRT) in June 2002 (Trugene HIV-1 Genotyping Assay, Siemens Healthcare Diagnostics GmbH, Eschborn, Germany) showed extensive resistance in the RT region (M41L, E44D, D67N, V118L, M184V, L210W, and T215Y) and the PR region (L10I, M46L, L63P, V82T, and L90M), and a tropism test in 2013 (envelope glycoprotein (gp)120 V3 loop sequencing) revealed a C-C chemokine receptor type 5 (CCR5) tropic virus with a false positive rate of 91.3% (geno2pheno co-receptor tool). 2020 BMC infectious diseases Conclusion HIV D67N;E44D;L10I;L210W;L63P;L90M;M184V;M41L;M46L;T215Y;V118L;V82T 194;188;251;214;263;279;207;182;257;225;200;269 198;192;255;219;267;283;212;186;261;230;205;273 Env;PR;RT 314;240;171 322;242;173 32264923 Multidrug-resistant HIV viral rebound during early syphilis: a case report. The test of plasma RNA showed wild-type virus in the PR and integrase region, but extensive resistances in the RT region (M41L, E44D, D67N, K70R, M184V, L210W and T215Y), and the test of plasma DNA showed the same resistance profile. 2020 BMC infectious diseases Conclusion HIV D67N;E44D;K70R;L210W;M184V;M41L;T215Y 134;128;140;153;146;122;163 138;132;144;158;151;126;168 IN;PR;RT 60;53;111 69;55;113 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Given the negative effect of M184V mutations on viral fitness, it is more plausible to the recycling of 3TC/FTC in second-line cART maintains the presence of M184V. 2020 Frontiers in microbiology Conclusion HIV M184V;M184V 29;158 34;163 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The majority of them had M184V mutations that could have been carried over from the first-line cART. 2020 Frontiers in microbiology Conclusion HIV M184V 25 30 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. However, V32I is a compensatory mutation that may be responsible for tethering the flaps to the active site through its contacts with I47V. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V;V32I 134;9 138;13 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. I47V HIV-1 mutation is involved in flap opening and the interaction between I47V and V32I tethers the flaps to the active site. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V;V32I;I47V 76;85;0 80;89;4 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. I54M and L90M may be responsible for asymmetric movement of the protease flaps. 2014 Discoveries (Craiova, Romania) Conclusion HIV L90M;I54M 9;0 13;4 PR 64 72 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. It contains only the I47V mutation and without the V32I mutation there is a loss in vdW contact volume between these two residues. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V;V32I 21;51 25;55 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Our results indicate a novel structural role for the I47V, V32I, I54M and L90M resistance mutations. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V;I54M;L90M;V32I 53;65;74;59 57;69;78;63 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Sequence analysis comparisons of the DetMDR protease isolates showed that DetMDR2 does not contain the V32I and I47V mutation combination. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V;V32I 112;103 116;107 PR 44 52 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. The V32I and I47V mutations play a structural role in tethering the flaps to the active site. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V;V32I 13;4 17;8 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Therefore, if I47V is the only mutation it may be responsible for promoting flap opening through the disruption of the vdW interactions between residues 32 and 47. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V 14 18 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Therefore, we postulate that I47V is responsible for flap opening. 2014 Discoveries (Craiova, Romania) Conclusion HIV I47V 29 33 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. In summary, we confirmed the expansion of HIV-1 CRF65_cpx in China and, surprisingly, found the natural presence of the V179D and K103R/V179D mutations in HIV-1 CRF65_cpx. 2020 BMC infectious diseases Conclusion HIV K103R;V179D;V179D 130;120;136 135;125;141 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Compound 26 turns out as the most potent inhibitor with EC50 values of 9.93, 10.5, 6.02, 18.9, 23.9 and 23.2 nmol/L against WT, L100I, K103N, Y181C, Y188L and E138K strains, respectively, being comparable to those of ETR. 2020 Acta pharmaceutica Sinica. B Conclusion HIV E138K;K103N;L100I;Y181C;Y188L 159;135;128;142;149 164;140;133;147;154 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. These compounds showed effective potency against WT and most of NNRTIs-resistant HIV-1 strain, especially to the challenging K103N mutation. 2020 Acta pharmaceutica Sinica. B Conclusion HIV K103N 125 130 NNRTI 64 70 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. The genotype resulted at day 15 after antiretroviral therapy was initiated and revealed clade B HIV-1 with G163R and S230R INSTI mutations, the latter present at a detection frequency of 16.2%, reported as conferring low-level DTG resistance. 2020 Medicine Conclusion HIV G163R;S230R 107;117 112;122 INSTI 123 128 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. Our findings suggest that there is need for close virological monitoring, use of NNRTI-sparing regimens, or HIV-1 genotyping for patients initiating ART in urban settings, especially with the presence of K65R mutation that jeopardizes the effectiveness of the current preferred first line ART. 2020 PloS one Conclusion HIV K65R 204 208 NNRTI 81 86 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. HIV drug resistance testing on the participant's month nine sample revealed the presence of both the M184V and the K65R mutations. 2020 BMC infectious diseases Conclusion HIV K65R;M184V 115;101 119;106 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. However, by 2 months the M184V mutation gained selective advantage and became dominant, and by 3 months, dual resistance was observed with the detection of the K65R mutations with nearly 100% resistant viral population. 2020 BMC infectious diseases Conclusion HIV K65R;M184V 160;25 164;30 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. K65R mutation is the signature TFV resistance mutation and confers intermediate/high-level resistance to TDF, didanosine (ddI), abacavir (ABC) and stavudine (D4T) and low/intermediate resistance to 3TC and FTC. 2020 BMC infectious diseases Conclusion HIV K65R 0 4 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. The M184V mutation is linked to FTC and 3TC high level resistance, whilst increasing susceptibility to thymidine analogue NRTIs. 2020 BMC infectious diseases Conclusion HIV M184V 4 9 NRTI 122 127 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. This study found major drug resistance mutations, E138A and K65R that respectively confer high level resistance to NNRTIs and NRTIs. 2020 Virology journal Conclusion HIV E138A;K65R 50;60 55;64 NNRTI;NRTI 115;126 121;131 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. Additional RAMs were H221HY for NNRTI and S147G for INSTI. 2020 Antimicrobial resistance and infection control Conclusion HIV H221H;H221Y;S147G 21;21;42 27;27;47 INSTI;NNRTI 52;32 57;37 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. Another GRT, covering HIV-1 integrase (IN) region, performed on the sample plasma aliquot, revealed major RAMs, L74I, E138KQ, G140A, Q148R, and E157Q, to integrase strand transfer inhibitors (INSTI) including raltegravir, dolutegravir, bictegravir and elvitegravir. 2020 Antimicrobial resistance and infection control Conclusion HIV E138K;E138Q;E157Q;G140A;L74I;Q148R 118;118;144;126;112;133 124;124;149;131;116;138 IN;IN;INSTI;IN 28;154;192;39 37;163;197;41 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. Detected RAMs were M41L, K70Q, V75I, Q151M, M184V and T215F for NRTI; K103N and V108I for NNRTI; and L10F, K20I, M36I, M46I, I47V, I54L, L63H, L76V, V82S and L89I for PI/r. 2020 Antimicrobial resistance and infection control Conclusion HIV I47V;I54L;K103N;K20I;K70Q;L10F;L63H;L76V;L89I;M184V;M36I;M41L;M46I;Q151M;T215F;V108I;V75I;V82S 125;131;70;107;25;101;137;143;158;44;113;19;119;37;54;80;31;149 129;135;75;111;29;105;141;147;162;49;117;23;123;42;59;85;35;153 NNRTI;NRTI;PI 90;64;167 95;68;169 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. Pending access to required innovative regimen, a salvage therapy guided by GRT was recommended, consisting of either "DRV/r(600mg x 2/day), saquinavir/r, TDF+3TC", or "3TC-monotherapy" which maintains M184V and as such limits the viral replicative fitness. 2020 Antimicrobial resistance and infection control Conclusion HIV M184V 201 206 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. Prior to ART re-initiation in 2010, genotypic resistance testing (GRT) results, interpreted throughout using Stanford HIVDB (http://www.hivdb.stanford.edu) and International AIDS Society mutations list, showed the presence of one resistance associated mutation (RAM) to NRTI (V75I), two non-NRTI RAMs (K103I, V108I). 2020 Antimicrobial resistance and infection control Conclusion HIV K103I;V108I;V75I 302;309;276 307;314;280 NNRTI;NRTI 287;270 295;274 AIDS 174 178 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. The first GRT (April 29, 2010) covered the protease (PR) and reverse transcriptase (RT) regions, with high-level resistance to first-generation NNRTI (K103I, V108I) and no major-RAM to NRTI and PI/r. 2020 Antimicrobial resistance and infection control Conclusion HIV K103I;V108I 151;158 156;163 RT;PR;NNRTI;NRTI;PI;PR;RT 61;43;144;185;194;53;84 82;51;149;189;196;55;86 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. The drug resistance-associated major mutations, K103N (6.67%) and Y181C (7.14%), were detected in RT genes, suggesting the emergence of TDR in Jakarta. 2020 Infectious disease reports Conclusion HIV K103N;Y181C 48;66 53;71 RT 98 100 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. In the current study, our simulations suggest different Mg2+ coordination in the active sites of the HIV-1 IN, the N155H variant, and the double mutant N155H+Q148H. 2020 Frontiers in molecular biosciences Conclusion HIV N155H;N155H;Q148H 115;152;158 120;157;163 IN 107 109 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Large conformational changes in the terminal nucleotide near one of the chains of the WT IN suggests that its vDNA terminal may be flexible, while no large conformational changes were observed in the terminal nucleotide of the N155H variant and the double mutant. 2020 Frontiers in molecular biosciences Conclusion HIV N155H 227 232 IN 89 91 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Possibly, other mutations that introduce long or positively charged side chains near the ions can cause resistance by a similar mechanism of Mg2+ ion pair disruption, for instance, in the mutants T66KI. 2020 Frontiers in molecular biosciences Conclusion HIV T66I;T66K 196;196 201;201 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. This is evidence for the hypothesis that claims N155H has stronger vDNA-IN interactions. 2020 Frontiers in molecular biosciences Conclusion HIV N155H 48 53 IN 72 74 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. We believe that the different conformation of ions in the N155H variant may impact the binding mode of the INSTIs since these drugs partially rely on metal-chelating groups to properly function. 2020 Frontiers in molecular biosciences Conclusion HIV N155H 58 63 INSTI 107 113 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Larger, prospective trials examining ART containing <3 active agents and the M184V/I mutation are needed to determine optimal ART for such patients. 2020 SAGE open medicine Conclusion HIV M184I;M184V 77;77 84;84 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Regimens containing 2-2.5 active agents were commonly prescribed in patients with M184V/I mutations and most patients were continued on 3TC or FTC despite the presence of resistance. 2020 SAGE open medicine Conclusion HIV M184I;M184V 82;82 89;89 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Regimens containing less than three active agents may maintain viral suppression in patients with the M184V/I mutation. 2020 SAGE open medicine Conclusion HIV M184I;M184V 102;102 109;109 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Infection studies in A549 cells suggest that the mutant strains display a replication efficiency comparable with MCC350, except for the T47S mutant. 2020 International journal of molecular sciences Conclusion HIV T47S 136 140 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Protein stability prediction programs foresee that the detected amino acid substitutions D69V, I115F, and S251F stabilize the VP1 protein, while the T47S mutation is suspected to destabilize the protein. 2020 International journal of molecular sciences Conclusion HIV D69V;I115F;S251F;T47S 89;95;106;149 93;100;111;153 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. In conclusion, we describe a rare case of a virological failure on the DTG/3TC/ABC regimen with the emergence of resistance to all INSTIs in a patient with pre-existing M184V/I mutation. 2020 Viruses Conclusion HIV M184I;M184V 169;169 176;176 INSTI 131 137 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. This case illustrates that DTG/3TC/ABC should be prescribed with caution to patients with pre-existing M184V/I mutation, a low CD4 cell count, and/or poor adherence. 2020 Viruses Conclusion HIV M184I;M184V 103;103 110;110 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. In conclusion, our results demonstrate that drug resistance mutations associated with INSTIs, including T97A, A128T, E157Q, and G163R, were detected among ART-naive HIV-1-infected adults in Guangdong, China, in 2018. 2020 Infection and drug resistance Conclusion HIV A128T;E157Q;G163R;T97A 110;117;128;104 115;122;133;108 INSTI 86 92 HIV infections 165 179 33466381 Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation. The role of Asn425 was further supported by the MD simulations of N425G mutant. 2021 Molecules (Basel, Switzerland) Conclusion HIV N425G 66 71 33466381 Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation. We have found that the N425G mutation increases the binding affinity but it does not induce the flexibility in gp120 due to a lack of flexible side chain interaction with NBD-557. 2021 Molecules (Basel, Switzerland) Conclusion HIV N425G 23 28 gp120 111 116 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. Using HTS-GRT, PI RAMs (V82A) and RTI RAMs (K65R, M184V or K103N) were identified in < 20% of the population that Sanger-based sequencing failed to identify, strengthening their role in detecting the acquired mutations early. 2021 BMC infectious diseases Conclusion HIV K103N;K65R;M184V;V82A 59;44;50;24 64;48;55;28 RT;PI 34;15 37;17 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. However, TDRM associated with INSTIs-treatment resistance, including E138K and E517Q were also detected in therapy- naive HIV patients in Southeast China. 2021 Drug design, development and therapy Conclusion HIV E138K;E517Q 69;79 74;84 INSTI 30 36 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Molecular modelling and interaction analysis provided novel insights into the effect of accessory mutations (E157Q and D232N) on HIV-1 CRF02_AG IN drug resistance. 2021 BMC infectious diseases Conclusion HIV D232N;E157Q 119;109 124;115 IN 144 146 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. According to the free energy surfaces of theside chain dihedral angle, the I66 side chain in the M66I-GS-6207 complex populates a higher free energy rotamer state to minimize the steric clash. 2021 Viruses Conclusion HIV M66I 97 101 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. By using a formula that decomposes the absolute binding free energy into contributions from two receptor conformational states, we show that the protein side chain reorganization plays a major role in the M66I resistance to GS-6207. 2021 Viruses Conclusion HIV M66I 205 209 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. In contrast, the corresponding conformational changes are largely absent in the I66 of the M66I-ZW-1261 and M66I-PF74 complexes, and in the WT-GS-6207. 2021 Viruses Conclusion HIV M66I;M66I 91;108 95;112 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. The experimental data show that the M66I mutation leads to an >84,000-fold reduction in the activity of GS-6207, a picomolar HIV-1 capsid-targeting antiviral, while the same mutation leads to only a 68-fold reduction in the activity of the newly designed antiviral ZW-1261 and a 83-fold loss in the activity of PF74. 2021 Viruses Conclusion HIV M66I 36 40 Capsid 131 137 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. This study provides plausible physical explanations for the mutation M66I that affects the three HIV-1 capsid-targeting antivirals differently at an atomic level, and could help to inform the design of new antivirals with improved resistance profiles. 2021 Viruses Conclusion HIV M66I 69 73 Capsid 103 109 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. To understand the physical mechanisms of M66I resistance for these antivirals, we used all-atom molecular dynamics free energy calculations to study the energetics, structures, and conformational free energy profiles of the species involved in the binding of these antivirals to the wild-type CA and the M66I mutant. 2021 Viruses Conclusion HIV M66I;M66I 41;304 45;308 Capsid 293 295 34063519 Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation. While drug resistance mutations are often attributed to the loss of direct or solvent-mediated protein-ligand interactions in the drug-mutant complex, in this study we demonstrate that the molecular basis for the M66I resistance mutation of GS-6207 is mainly due to the free energy cost of the drug-induced protein side chain reorganization in the mutant protein. 2021 Viruses Conclusion HIV M66I 213 217 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. A pretreatment genotype, which included INI testing, revealed an HIV-1 subtype B along with an L74I (RT) mutation conferring high-level resistance to didanosine and intermediate-level resistance to abacavir. 2021 Open forum infectious diseases Conclusion HIV L74I 95 99 IN;RT 40;101 43;103 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. A repeat viral load was 98 000 copies/mL, and an updated genotype revealed an M184V (RT) mutation conferring resistance to lamivudine and FTC in addition to the previously seen L74I (RT) mutation. 2021 Open forum infectious diseases Conclusion HIV L74I;M184V 177;78 181;83 RT;RT 85;183 87;185 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. At follow-up the next month (week 37), he had an HIV RNA load of 14 095 copies/mL and a newly acquired R263K mutation (conferring low-level resistance to BIC) along with the previously documented M184V (RT) and L74I (RT) mutations. 2021 Open forum infectious diseases Conclusion HIV L74I;M184V;R263K 211;196;103 215;201;108 RT;RT 203;217 205;219 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. In conclusion, the possibility of a reduced efficacy of the 3TC-DTG DT should be kept in mind when previous virological failures are present and past TAMS and M184V/I are documented, particularly for patients with limited duration of virological suppression. 2021 Open forum infectious diseases Conclusion HIV M184I;M184V 159;159 166;166 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Using CRISPR/Cas9 to genetically ablate IP6 biosynthesis, we showed that these resulting HIV-1K359A/T371I virions are less dependent on cellular inositol phosphate levels. 2021 Retrovirology Conclusion HIV T371I 100 105 Capsid 13 15 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. We identified a single-site revertant mutation, T371I, that rescues replication competence of the IP6-binding-deficient mutant HIV-1K359A. 2021 Retrovirology Conclusion HIV T371I 48 53 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Although the single amino acid change in a previous report did not markedly increase the affinity of AnkGAG1D4, the intracellular activity of AnkGAG1D4-S45Y demonstrated distinctly notable performance. 2021 Biomolecules Conclusion HIV S45Y 152 156 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Our current results underscore the significance of AnkGAG1D4-S45Y for enhancing antiviral activity in either WT HIV-1 NL4-3 or MIR virus. 2021 Biomolecules Conclusion HIV S45Y 61 65 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. Among the few participants with virologic failure, development of RPV-RAMs (K101E and Y181C) was infrequent. 2022 Journal of the International AIDS Society Conclusion HIV K101E;Y181C 76;86 82;91 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In particular, mutations L449F, P453L and Y484P have shown a significant correlation with several major and/or accessory protease resistance mutations. 2022 Scientific reports Conclusion HIV L449F;P453L;Y484P 25;32;42 30;37;47 PR 121 129 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. The pan European EuResist Integrated Database (EIDB) was queried for cases satisfying the following criteria: a) patient is 18 years or older, (b) RPV was a part of their first-line ART regimen, (c) patient followed ART for more than 40 weeks, (d) the E138A mutation was present at baseline and there were no other RPV resistance mutations, and (e) there was an absence of any major NRTI mutations. 2022 Clinical case reports Conclusion HIV E138A 252 257 NRTI 383 387 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. At the point of CSF escape diagnosis, the CD4 cell count was 180 cells/mm3, and both plasma and CSF harbored the same NRTI M184V mutation. 2022 Journal of medical case reports Conclusion HIV M184V 123 128 NRTI 118 122 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. During subsequent years, the plasma resistance pattern reverted to susceptible for the NRTI/NNRTIs; however the PI mutation L89V appeared, only later to revert to fully susceptible again. 2022 Journal of medical case reports Conclusion HIV L89V 124 128 NNRTI;NRTI;PI 92;87;112 98;91;114 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. However, discordantly, the accessory nonpolymorphic PI T74TP mutation mixed with wild type appeared only in the plasma but not CSF. 2022 Journal of medical case reports Conclusion HIV T74P;T74T 55;55 60;60 PI 52 54 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. The HIV-1 pol gene genotypic resistance analysis showed development of the NRTI M184V mutation, and NNRTI K103N and E138EK mutations in plasma, respectively. 2022 Journal of medical case reports Conclusion HIV E138E;E138K;K103N;M184V 116;116;106;80 122;122;111;85 NNRTI;NRTI;Pol 100;75;10 105;79;13 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. The nonpolymorphic NNRTI K103N mutation causes high-level resistance to efavirenz (EFV), and E138K mutation causes potential low-level cross-resistance to EFV, which was discontinued together with 3TC. 2022 Journal of medical case reports Conclusion HIV E138K;K103N 93;25 98;30 NNRTI 19 24 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. The NRTI M184V mutation results in high-level in vitro resistance to lamivudine (3TC). 2022 Journal of medical case reports Conclusion HIV M184V 9 14 NRTI 4 8 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. The PI L89V mutation may contribute to reduced PI susceptibility. 2022 Journal of medical case reports Conclusion HIV L89V 7 11 PI;PI 4;47 6;49 35393931 HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission. Sanger sequencing identified resistance-associated mutations (RAM) M184V and K65R conferring resistance to both FTC and TDF, and V108I and E138A conferring resistance to nevirapine (NVP) and rilpivirine (RPV). 2022 Euro surveillance Conclusion HIV E138A;K65R;M184V;V108I 139;77;65;129 144;81;72;134 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. In the recent study, we investigated the role of the M46I mutation on the binding of saquinavir (SQ) and HIV-1 protease. 2022 Viruses Conclusion HIV M46I 53 57 PR 111 119 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. Overall, the results indicate that the M46I mutation largely affects the dynamics of the flap region of the protease, which leads to the decreased interaction between mutated protease and saquinavir. 2022 Viruses Conclusion HIV M46I 39 43 PR;PR 108;175 116;183 35458427 Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation. The M46I mutation produced an alteration in the beta-sheet (near the flap region) structure of HIV-1 protease. 2022 Viruses Conclusion HIV M46I 4 8 PR 101 109 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. The genetic barrier analysis showed that subtype C had a high genetic barrier to acquiring the G140C and G140S mutations, highlighting that the Q148H/K/R mutation DTG resistance pathway was selected less in subtype C. 2022 Viruses Conclusion HIV G140C;G140S;Q148H;Q148K;Q148R 95;105;144;144;144 100;110;153;153;153 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Apart from all the key neuropathogenic Tat protein signatures, R57S present in Tat subtype C may contribute to the lower level of TAR interaction, transactivation, and underlying neuropathophysiology when compared to Tat subtype B. 2022 Frontiers in microbiology Conclusion HIV R57S 63 67 Tat;Tat;Tat 39;79;217 42;82;220 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. E89G 2005 AIDS research and therapy Table HIV E89G 0 4 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. K65R 2005 AIDS research and therapy Table HIV K65R 0 4 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. L74V 2005 AIDS research and therapy Table HIV L74V 0 4 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. M184V 2005 AIDS research and therapy Table HIV M184V 0 5 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. M41L 2005 AIDS research and therapy Table HIV M41L 0 4 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. N255D 2005 AIDS research and therapy Table HIV N255D 0 5 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. N265D 2005 AIDS research and therapy Table HIV N265D 0 5 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. T215Y 2005 AIDS research and therapy Table HIV T215Y 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. F223A 2006 Retrovirology Table HIV F223A 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. I267A 2006 Retrovirology Table HIV I267A 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. I268A 2006 Retrovirology Table HIV I268A 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. K244A 2006 Retrovirology Table HIV K244A 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. R224A 2006 Retrovirology Table HIV R224A 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. R262A 2006 Retrovirology Table HIV R262A 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. W243A 2006 Retrovirology Table HIV W243A 0 5 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Y226A 2006 Retrovirology Table HIV Y226A 0 5 16956392 HIV-2 Protease resistance defined in yeast cells. I54M 2006 Retrovirology Table HIV I54M 0 4 16956392 HIV-2 Protease resistance defined in yeast cells. K45R 2006 Retrovirology Table HIV K45R 0 4 16956392 HIV-2 Protease resistance defined in yeast cells. L90M 2006 Retrovirology Table HIV L90M 0 4 16956392 HIV-2 Protease resistance defined in yeast cells. L99F 2006 Retrovirology Table HIV L99F 0 4 16956392 HIV-2 Protease resistance defined in yeast cells. M76V 2006 Retrovirology Table HIV M76V 0 4 16956392 HIV-2 Protease resistance defined in yeast cells. V20A 2006 Retrovirology Table HIV V20A 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. A158P 2007 Retrovirology Table HIV A158P 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. A158T 2007 Retrovirology Table HIV A158T 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. A98G 2007 Retrovirology Table HIV A98G 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. D177N 2007 Retrovirology Table HIV D177N 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. D218E 2007 Retrovirology Table HIV D218E 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. E169K 2007 Retrovirology Table HIV E169K 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. E194K 2007 Retrovirology Table HIV E194K 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. E203G 2007 Retrovirology Table HIV E203G 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. E40Q 2007 Retrovirology Table HIV E40Q 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. F116W 2007 Retrovirology Table HIV F116W 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. G196K 2007 Retrovirology Table HIV G196K 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. G196R 2007 Retrovirology Table HIV G196R 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. G359S 2007 Retrovirology Table HIV G359S 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. H208L 2007 Retrovirology Table HIV H208L 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. H208Q 2007 Retrovirology Table HIV H208Q 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. H221P 2007 Retrovirology Table HIV H221P 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. H221Y 2007 Retrovirology Table HIV H221Y 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. I159L 2007 Retrovirology Table HIV I159L 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. I159V 2007 Retrovirology Table HIV I159V 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. I178M 2007 Retrovirology Table HIV I178M 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. I195T 2007 Retrovirology Table HIV I195T 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. I202V 2007 Retrovirology Table HIV I202V 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. I275R 2007 Retrovirology Table HIV I275R 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K11N 2007 Retrovirology Table HIV K11N 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K154E 2007 Retrovirology Table HIV K154E 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K154Q 2007 Retrovirology Table HIV K154Q 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K173Q 2007 Retrovirology Table HIV K173Q 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K20R 2007 Retrovirology Table HIV K20R 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K219E 2007 Retrovirology Table HIV K219E 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K219G 2007 Retrovirology Table HIV K219G 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K219H 2007 Retrovirology Table HIV K219H 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K219N 2007 Retrovirology Table HIV K219N 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K219Q 2007 Retrovirology Table HIV K219Q 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K219R 2007 Retrovirology Table HIV K219R 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K22R 2007 Retrovirology Table HIV K22R 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K275K/R 2007 Retrovirology Table HIV K275K;K275R 0;0 7;7 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K275R 2007 Retrovirology Table HIV K275R 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K45Q 2007 Retrovirology Table HIV K45Q 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K64R 2007 Retrovirology Table HIV K64R 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K65K/R 2007 Retrovirology Table HIV K65K;K65R 0;0 6;6 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K65R 2007 Retrovirology Table HIV K65R 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K65R/K 2007 Retrovirology Table HIV K65K;K65R 0;0 6;6 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70E 2007 Retrovirology Table HIV K70E 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70E/K 2007 Retrovirology Table HIV K70E;K70K 0;0 6;6 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70E/Q 2007 Retrovirology Table HIV K70E;K70Q 0;0 6;6 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70H 2007 Retrovirology Table HIV K70H 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70K 2007 Retrovirology Table HIV K70K 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70K/E 2007 Retrovirology Table HIV K70E;K70K 0;0 6;6 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70N 2007 Retrovirology Table HIV K70N 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70Q 2007 Retrovirology Table HIV K70Q 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. K70T 2007 Retrovirology Table HIV K70T 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. L210V 2007 Retrovirology Table HIV L210V 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. L214F 2007 Retrovirology Table HIV L214F 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. L214L/F 2007 Retrovirology Table HIV L214F;L214L 0;0 7;7 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. M357N 2007 Retrovirology Table HIV M357N 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. M357S 2007 Retrovirology Table HIV M357S 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. M357T 2007 Retrovirology Table HIV M357T 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. M357T/M 2007 Retrovirology Table HIV M357M;M357T 0;0 7;7 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. M41L 2007 Retrovirology Table HIV M41L 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. N218E 2007 Retrovirology Table HIV N218E 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. P150S 2007 Retrovirology Table HIV P150S 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. P294Q 2007 Retrovirology Table HIV P294Q 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Q145H 2007 Retrovirology Table HIV Q145H 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Q222L 2007 Retrovirology Table HIV Q222L 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Q248N 2007 Retrovirology Table HIV Q248N 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. R172I 2007 Retrovirology Table HIV R172I 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. R172S 2007 Retrovirology Table HIV R172S 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. R199I 2007 Retrovirology Table HIV R199I 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. R199K 2007 Retrovirology Table HIV R199K 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. R199M 2007 Retrovirology Table HIV R199M 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. R277K 2007 Retrovirology Table HIV R277K 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. S251N 2007 Retrovirology Table HIV S251N 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. S68G 2007 Retrovirology Table HIV S68G 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. S68K 2007 Retrovirology Table HIV S68K 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. S68N 2007 Retrovirology Table HIV S68N 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. S68R 2007 Retrovirology Table HIV S68R 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. S68S 2007 Retrovirology Table HIV S68S 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. T139A 2007 Retrovirology Table HIV T139A 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. T39A 2007 Retrovirology Table HIV T39A 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. T69I 2007 Retrovirology Table HIV T69I 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. T69N 2007 Retrovirology Table HIV T69N 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V118I 2007 Retrovirology Table HIV V118I 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V179G 2007 Retrovirology Table HIV V179G 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V179I 2007 Retrovirology Table HIV V179I 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V195L 2007 Retrovirology Table HIV V195L 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V21I 2007 Retrovirology Table HIV V21I 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V245M 2007 Retrovirology Table HIV V245M 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V75I 2007 Retrovirology Table HIV V75I 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V75L 2007 Retrovirology Table HIV V75L 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V75V/L 2007 Retrovirology Table HIV V75L;V75V 0;0 6;6 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V7I 2007 Retrovirology Table HIV V7I 0 3 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. V8I 2007 Retrovirology Table HIV V8I 0 3 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. W88S 2007 Retrovirology Table HIV W88S 0 4 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Y115F 2007 Retrovirology Table HIV Y115F 0 5 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Y181C 2007 Retrovirology Table HIV Y181C 0 5 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. D51E 2007 Retrovirology Table HIV D51E 0 4 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. D51N 2007 Retrovirology Table HIV D51N 0 4 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. D51Q 2007 Retrovirology Table HIV D51Q 0 4 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I 2007 PLoS medicine Table HIV N348I 0 5 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. L90M 2008 Retrovirology Table HIV L90M 0 4 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. E248D 2008 Retrovirology Table HIV E248D 0 5 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. E297H 2008 Retrovirology Table HIV E297H 0 5 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. E40F 2008 Retrovirology Table HIV E40F 0 4 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. I293V 2008 Retrovirology Table HIV I293V 0 5 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. K43E 2008 Retrovirology Table HIV K43E 0 4 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. M41L 2008 Retrovirology Table HIV M41L 0 4 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. R211K 2008 Retrovirology Table HIV R211K 0 5 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. T200I 2008 Retrovirology Table HIV T200I 0 5 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. T215Y 2008 Retrovirology Table HIV T215Y 0 5 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. V245T 2008 Retrovirology Table HIV V245T 0 5 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). A10L 2008 PloS one Table HIV A10L 0 4 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). A44L 2008 PloS one Table HIV A44L 0 4 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). A46R 2008 PloS one Table HIV A46R 0 4 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). C12L 2008 PloS one Table HIV C12L 0 4 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. A360V 2008 The Journal of biological chemistry Table HIV A360V 0 5 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. N348I 2008 The Journal of biological chemistry Table HIV N348I 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. G190A 2008 The Journal of infectious diseases Table HIV G190A 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. K101E 2008 The Journal of infectious diseases Table HIV K101E 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. K103N 2008 The Journal of infectious diseases Table HIV K103N 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. K103T 2008 The Journal of infectious diseases Table HIV K103T 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. V106A 2008 The Journal of infectious diseases Table HIV V106A 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. V106M 2008 The Journal of infectious diseases Table HIV V106M 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Y181C 2008 The Journal of infectious diseases Table HIV Y181C 0 5 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. Y188C 2008 The Journal of infectious diseases Table HIV Y188C 0 5 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. G190A 2008 The Journal of infectious diseases Table HIV G190A 0 5 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. K101E 2008 The Journal of infectious diseases Table HIV K101E 0 5 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. K103N 2008 The Journal of infectious diseases Table HIV K103N 0 5 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. V106A 2008 The Journal of infectious diseases Table HIV V106A 0 5 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. V106M 2008 The Journal of infectious diseases Table HIV V106M 0 5 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. Y181C 2008 The Journal of infectious diseases Table HIV Y181C 0 5 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. Y188C 2008 The Journal of infectious diseases Table HIV Y188C 0 5 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. C67A 2008 Journal of medicinal chemistry Table HIV C67A 0 4 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. C95A 2008 Journal of medicinal chemistry Table HIV C95A 0 4 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. L33I 2008 Journal of medicinal chemistry Table HIV L33I 0 4 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. L63I 2008 Journal of medicinal chemistry Table HIV L63I 0 4 18808097 Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir. V32I 2008 Journal of medicinal chemistry Table HIV V32I 0 4 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. N283T 2008 Retrovirology Table HIV N283T 0 5 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. T283N 2008 Retrovirology Table HIV T283N 0 5 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. A71T 2009 Infection, genetics and evolution Table HIV A71T 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. A71V 2009 Infection, genetics and evolution Table HIV A71V 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. D30N 2009 Infection, genetics and evolution Table HIV D30N 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. F53L 2009 Infection, genetics and evolution Table HIV F53L 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. G48V 2009 Infection, genetics and evolution Table HIV G48V 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. G73S 2009 Infection, genetics and evolution Table HIV G73S 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. I50V 2009 Infection, genetics and evolution Table HIV I50V 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. I54V 2009 Infection, genetics and evolution Table HIV I54V 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. I84V 2009 Infection, genetics and evolution Table HIV I84V 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. K20I 2009 Infection, genetics and evolution Table HIV K20I 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. K20M 2009 Infection, genetics and evolution Table HIV K20M 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. K20R 2009 Infection, genetics and evolution Table HIV K20R 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. K20T 2009 Infection, genetics and evolution Table HIV K20T 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. L10F 2009 Infection, genetics and evolution Table HIV L10F 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. L10I 2009 Infection, genetics and evolution Table HIV L10I 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. L10V 2009 Infection, genetics and evolution Table HIV L10V 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. L24I 2009 Infection, genetics and evolution Table HIV L24I 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. L33F 2009 Infection, genetics and evolution Table HIV L33F 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. L63P 2009 Infection, genetics and evolution Table HIV L63P 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. L90M 2009 Infection, genetics and evolution Table HIV L90M 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. M36I 2009 Infection, genetics and evolution Table HIV M36I 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. M46I 2009 Infection, genetics and evolution Table HIV M46I 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. M46L 2009 Infection, genetics and evolution Table HIV M46L 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. N88D 2009 Infection, genetics and evolution Table HIV N88D 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. N88S 2009 Infection, genetics and evolution Table HIV N88S 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. V77I 2009 Infection, genetics and evolution Table HIV V77I 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. V82A 2009 Infection, genetics and evolution Table HIV V82A 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. V82F 2009 Infection, genetics and evolution Table HIV V82F 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. V82L 2009 Infection, genetics and evolution Table HIV V82L 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. V82S 2009 Infection, genetics and evolution Table HIV V82S 0 4 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. V82T 2009 Infection, genetics and evolution Table HIV V82T 0 4 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. H121N 2009 Laboratory investigation; a journal of technical methods and pathology Table HIV H121N 0 5 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Y955C 2009 Laboratory investigation; a journal of technical methods and pathology Table HIV Y955C 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. G190A 2009 PloS one Table HIV G190A 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. G190A/E 2009 PloS one Table HIV G190A;G190E 0;0 7;7 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. G190E 2009 PloS one Table HIV G190E 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. K101E 2009 PloS one Table HIV K101E 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. K103N 2009 PloS one Table HIV K103N 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. V106A/M 2009 PloS one Table HIV V106A;V106M 0;0 7;7 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. V106M 2009 PloS one Table HIV V106M 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. V108I 2009 PloS one Table HIV V108I 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. Y181C 2009 PloS one Table HIV Y181C 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. Y188C 2009 PloS one Table HIV Y188C 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. Y188C/H 2009 PloS one Table HIV Y188C;Y188H 0;0 7;7 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. Y188H 2009 PloS one Table HIV Y188H 0 5 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. Gly-149 to Lys 2009 PloS one Table HIV G149K 0 14 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. D67N 2009 Clinical infectious diseases Table HIV D67N 0 4 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. F227L 2009 Clinical infectious diseases Table HIV F227L 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. G190A 2009 Clinical infectious diseases Table HIV G190A 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. K103N 2009 Clinical infectious diseases Table HIV K103N 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. K103R 2009 Clinical infectious diseases Table HIV K103R 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. K238T 2009 Clinical infectious diseases Table HIV K238T 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. M184I 2009 Clinical infectious diseases Table HIV M184I 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. M184V 2009 Clinical infectious diseases Table HIV M184V 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. M41L 2009 Clinical infectious diseases Table HIV M41L 0 4 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. V106M 2009 Clinical infectious diseases Table HIV V106M 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Y181C 2009 Clinical infectious diseases Table HIV Y181C 0 5 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Y181H 2009 Clinical infectious diseases Table HIV Y181H 0 5 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Gln155Asn 2009 Biomacromolecules Table HIV Q155N 0 9 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Glu159Asp 2009 Biomacromolecules Table HIV E159D 0 9 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. I150I 2009 Biomacromolecules Table HIV I150I 0 5 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Met185Ala 2009 Biomacromolecules Table HIV M185A 0 9 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. S149I 2009 Biomacromolecules Table HIV S149I 0 5 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. T148I 2009 Biomacromolecules Table HIV T148I 0 5 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Trp184Ala 2009 Biomacromolecules Table HIV W184A 0 9 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. K65R 2009 Retrovirology Table HIV K65R 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. D60E 2009 AIDS (London, England) Table HIV D60E 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. E35D 2009 AIDS (London, England) Table HIV E35D 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. E65D 2009 AIDS (London, England) Table HIV E65D 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. F53F/L 2009 AIDS (London, England) Table HIV F53F;F53L 0;0 6;6 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. G16E 2009 AIDS (London, England) Table HIV G16E 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. H69K 2009 AIDS (London, England) Table HIV H69K 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. H69Y 2009 AIDS (London, England) Table HIV H69Y 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. I13I 2009 AIDS (London, England) Table HIV I13I 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. I13V 2009 AIDS (London, England) Table HIV I13V 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. I15V 2009 AIDS (London, England) Table HIV I15V 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. I64V 2009 AIDS (London, England) Table HIV I64V 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. I72I/V 2009 AIDS (London, England) Table HIV I72I;I72V 0;0 6;6 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. I72V 2009 AIDS (London, England) Table HIV I72V 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. K14R 2009 AIDS (London, England) Table HIV K14R 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. K20K/R 2009 AIDS (London, England) Table HIV K20K;K20R 0;0 6;6 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. K20R 2009 AIDS (London, England) Table HIV K20R 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. K70R 2009 AIDS (London, England) Table HIV K70R 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. L10V 2009 AIDS (London, England) Table HIV L10V 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. L33F 2009 AIDS (London, England) Table HIV L33F 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. L33I 2009 AIDS (London, England) Table HIV L33I 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. L63E 2009 AIDS (London, England) Table HIV L63E 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. L63Q 2009 AIDS (London, England) Table HIV L63Q 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. L63T 2009 AIDS (London, England) Table HIV L63T 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. M36I 2009 AIDS (London, England) Table HIV M36I 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. R41K 2009 AIDS (London, England) Table HIV R41K 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. R57K 2009 AIDS (London, England) Table HIV R57K 0 4 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. T4T 2009 AIDS (London, England) Table HIV T4T 0 3 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. V75V/I 2009 AIDS (London, England) Table HIV V75I;V75V 0;0 6;6 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. D67N 2009 PloS one Table HIV D67N 0 4 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. G190A 2009 PloS one Table HIV G190A 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. K101E 2009 PloS one Table HIV K101E 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. K219E 2009 PloS one Table HIV K219E 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. K70R 2009 PloS one Table HIV K70R 0 4 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. M184V 2009 PloS one Table HIV M184V 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. M41L 2009 PloS one Table HIV M41L 0 4 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. T215F 2009 PloS one Table HIV T215F 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. T69N 2009 PloS one Table HIV T69N 0 4 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. K65R 2009 AIDS (London, England) Table HIV K65R 0 4 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. K70E 2009 AIDS (London, England) Table HIV K70E 0 4 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. M184V 2009 AIDS (London, England) Table HIV M184V 0 5 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Q151M 2009 AIDS (London, England) Table HIV Q151M 0 5 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. K103N 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV K103N 0 5 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Y181C 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV Y181C 0 5 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. L64A 2009 PloS one Table HIV L64A 0 4 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Q77R 2009 PloS one Table HIV Q77R 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. A30T 2009 AIDS research and human retroviruses Table HIV A30T 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. E137K 2009 AIDS research and human retroviruses Table HIV E137K 0 5 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. G36D/E 2009 AIDS research and human retroviruses Table HIV G36D;G36E 0;0 6;6 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. I37V 2009 AIDS research and human retroviruses Table HIV I37V 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. L44M 2009 AIDS research and human retroviruses Table HIV L44M 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. L45M 2009 AIDS research and human retroviruses Table HIV L45M 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. N126D 2009 AIDS research and human retroviruses Table HIV N126D 0 5 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. N126K 2009 AIDS research and human retroviruses Table HIV N126K 0 5 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. N42S 2009 AIDS research and human retroviruses Table HIV N42S 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. N42T 2009 AIDS research and human retroviruses Table HIV N42T 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. N43D 2009 AIDS research and human retroviruses Table HIV N43D 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. N43K 2009 AIDS research and human retroviruses Table HIV N43K 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Q39R 2009 AIDS research and human retroviruses Table HIV Q39R 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Q40H 2009 AIDS research and human retroviruses Table HIV Q40H 0 4 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. S138A 2009 AIDS research and human retroviruses Table HIV S138A 0 5 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. V38A 2009 AIDS research and human retroviruses Table HIV V38A 0 4 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. A98G 2009 AIDS research and human retroviruses Table HIV A98G 0 4 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. G190A 2009 AIDS research and human retroviruses Table HIV G190A 0 5 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. G190A/S 2009 AIDS research and human retroviruses Table HIV G190A;G190S 0;0 7;7 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. K101E/P 2009 AIDS research and human retroviruses Table HIV K101E;K101P 0;0 7;7 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. K103N 2009 AIDS research and human retroviruses Table HIV K103N 0 5 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. K103N/S 2009 AIDS research and human retroviruses Table HIV K103N;K103S 0;0 7;7 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. K103R 2009 AIDS research and human retroviruses Table HIV K103R 0 5 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. L100I 2009 AIDS research and human retroviruses Table HIV L100I 0 5 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. M230L 2009 AIDS research and human retroviruses Table HIV M230L 0 5 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. V106A/M 2009 AIDS research and human retroviruses Table HIV V106A;V106M 0;0 7;7 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. V179D 2009 AIDS research and human retroviruses Table HIV V179D 0 5 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Y181C 2009 AIDS research and human retroviruses Table HIV Y181C 0 5 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Y181C/I 2009 AIDS research and human retroviruses Table HIV Y181C;Y181I 0;0 7;7 19552593 In utero HIV infection is associated with an increased risk of nevirapine resistance in ugandan infants who were exposed to perinatal single dose nevirapine. Y188C/H 2009 AIDS research and human retroviruses Table HIV Y188C;Y188H 0;0 7;7 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. G273A 2009 PloS one Table HIV G273A 0 5 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. I274A 2009 PloS one Table HIV I274A 0 5 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. K275A 2009 PloS one Table HIV K275A 0 5 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. R277A 2009 PloS one Table HIV R277A 0 5 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. V276A 2009 PloS one Table HIV V276A 0 5 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Y271A 2009 PloS one Table HIV Y271A 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. D60E 2009 BMC infectious diseases Table HIV D60E 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. D67N 2009 BMC infectious diseases Table HIV D67N 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. G16E 2009 BMC infectious diseases Table HIV G16E 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. G190A 2009 BMC infectious diseases Table HIV G190A 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. H69K 2009 BMC infectious diseases Table HIV H69K 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. I13V 2009 BMC infectious diseases Table HIV I13V 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. I62V 2009 BMC infectious diseases Table HIV I62V 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. I64M 2009 BMC infectious diseases Table HIV I64M 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. I64V 2009 BMC infectious diseases Table HIV I64V 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. I93L 2009 BMC infectious diseases Table HIV I93L 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. K101E 2009 BMC infectious diseases Table HIV K101E 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. K101P 2009 BMC infectious diseases Table HIV K101P 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. K103N 2009 BMC infectious diseases Table HIV K103N 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. K20R 2009 BMC infectious diseases Table HIV K20R 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. K219Q 2009 BMC infectious diseases Table HIV K219Q 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. K65R 2009 BMC infectious diseases Table HIV K65R 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. K70R 2009 BMC infectious diseases Table HIV K70R 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. L10I 2009 BMC infectious diseases Table HIV L10I 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. L10V 2009 BMC infectious diseases Table HIV L10V 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. L210W 2009 BMC infectious diseases Table HIV L210W 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. L33V 2009 BMC infectious diseases Table HIV L33V 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. L63P 2009 BMC infectious diseases Table HIV L63P 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. M184I 2009 BMC infectious diseases Table HIV M184I 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. M184V 2009 BMC infectious diseases Table HIV M184V 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. M36I 2009 BMC infectious diseases Table HIV M36I 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. M36V 2009 BMC infectious diseases Table HIV M36V 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. M41L 2009 BMC infectious diseases Table HIV M41L 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. T215F 2009 BMC infectious diseases Table HIV T215F 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. V108I 2009 BMC infectious diseases Table HIV V108I 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. V179T 2009 BMC infectious diseases Table HIV V179T 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. V75I 2009 BMC infectious diseases Table HIV V75I 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. V77I 2009 BMC infectious diseases Table HIV V77I 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. V82I 2009 BMC infectious diseases Table HIV V82I 0 4 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. Y181C 2009 BMC infectious diseases Table HIV Y181C 0 5 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. Y188C 2009 BMC infectious diseases Table HIV Y188C 0 5 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. G36D 2009 AIDS research and human retroviruses Table HIV G36D 0 4 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. V38A 2009 AIDS research and human retroviruses Table HIV V38A 0 4 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. V38E 2009 AIDS research and human retroviruses Table HIV V38E 0 4 19619009 Altered bystander apoptosis induction and pathogenesis of enfuvirtide-resistant HIV type 1 Env mutants. V38M 2009 AIDS research and human retroviruses Table HIV V38M 0 4 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. A98G 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV A98G 0 4 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. E138A 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV E138A 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. G190A/S 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV G190A;G190S 0;0 7;7 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. H221Y 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV H221Y 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. I142V 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV I142V 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. K101E/H 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV K101E;K101H 0;0 7;7 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. K103N 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV K103N 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. K64R 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV K64R 0 4 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. L100I 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV L100I 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. M230L 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV M230L 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. T200A 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV T200A 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. V106I 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV V106I 0 5 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. V179D/F 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV V179D;V179F 0;0 7;7 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. V60I 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV V60I 0 4 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. V90I 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV V90I 0 4 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Y181C/I 2009 Journal of acquired immune deficiency syndromes (1999) Table HIV Y181C;Y181I 0;0 7;7 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. K103N 2009 Beilstein journal of organic chemistry Table HIV K103N 0 5 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. Y181C 2009 Beilstein journal of organic chemistry Table HIV Y181C 0 5 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R 2009 The Journal of biological chemistry Table HIV K65R 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. A62V 2005 Journal of the International AIDS Society Table HIV A62V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. A71T 2005 Journal of the International AIDS Society Table HIV A71T 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. D67N 2005 Journal of the International AIDS Society Table HIV D67N 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. E44A/D 2005 Journal of the International AIDS Society Table HIV E44A;E44D 0;0 6;6 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. E44D 2005 Journal of the International AIDS Society Table HIV E44D 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. F116Y 2005 Journal of the International AIDS Society Table HIV F116Y 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. F77G 2005 Journal of the International AIDS Society Table HIV F77G 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. F77L 2005 Journal of the International AIDS Society Table HIV F77L 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. G190A 2005 Journal of the International AIDS Society Table HIV G190A 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. G190S 2005 Journal of the International AIDS Society Table HIV G190S 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. G333A 2005 Journal of the International AIDS Society Table HIV G333A 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. G48V 2005 Journal of the International AIDS Society Table HIV G48V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. G73S 2005 Journal of the International AIDS Society Table HIV G73S 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. I47V 2005 Journal of the International AIDS Society Table HIV I47V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. I50V 2005 Journal of the International AIDS Society Table HIV I50V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. I54L 2005 Journal of the International AIDS Society Table HIV I54L 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. I54M 2005 Journal of the International AIDS Society Table HIV I54M 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. I54V 2005 Journal of the International AIDS Society Table HIV I54V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. I84V 2005 Journal of the International AIDS Society Table HIV I84V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. K103N 2005 Journal of the International AIDS Society Table HIV K103N 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. K20M 2005 Journal of the International AIDS Society Table HIV K20M 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. K20R 2005 Journal of the International AIDS Society Table HIV K20R 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. K219E 2005 Journal of the International AIDS Society Table HIV K219E 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. K219Q 2005 Journal of the International AIDS Society Table HIV K219Q 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. K65R 2005 Journal of the International AIDS Society Table HIV K65R 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. K70R 2005 Journal of the International AIDS Society Table HIV K70R 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L100I 2005 Journal of the International AIDS Society Table HIV L100I 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L10F 2005 Journal of the International AIDS Society Table HIV L10F 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L10I 2005 Journal of the International AIDS Society Table HIV L10I 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L10R 2005 Journal of the International AIDS Society Table HIV L10R 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L10V 2005 Journal of the International AIDS Society Table HIV L10V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L210W 2005 Journal of the International AIDS Society Table HIV L210W 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L24I 2005 Journal of the International AIDS Society Table HIV L24I 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L74V 2005 Journal of the International AIDS Society Table HIV L74V 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. L90M 2005 Journal of the International AIDS Society Table HIV L90M 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. M184V 2005 Journal of the International AIDS Society Table HIV M184V 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. M230L 2005 Journal of the International AIDS Society Table HIV M230L 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. M36I 2005 Journal of the International AIDS Society Table HIV M36I 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. M41L 2005 Journal of the International AIDS Society Table HIV M41L 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. M46I 2005 Journal of the International AIDS Society Table HIV M46I 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. M46L 2005 Journal of the International AIDS Society Table HIV M46L 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. N88D 2005 Journal of the International AIDS Society Table HIV N88D 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. P225H 2005 Journal of the International AIDS Society Table HIV P225H 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. P236L 2005 Journal of the International AIDS Society Table HIV P236L 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Q151M 2005 Journal of the International AIDS Society Table HIV Q151M 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. T215F 2005 Journal of the International AIDS Society Table HIV T215F 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. T215Y 2005 Journal of the International AIDS Society Table HIV T215Y 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V106A 2005 Journal of the International AIDS Society Table HIV V106A 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V108I 2005 Journal of the International AIDS Society Table HIV V108I 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V118I 2005 Journal of the International AIDS Society Table HIV V118I 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V32I 2005 Journal of the International AIDS Society Table HIV V32I 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V75I 2005 Journal of the International AIDS Society Table HIV V75I 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V77I 2005 Journal of the International AIDS Society Table HIV V77I 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V82A 2005 Journal of the International AIDS Society Table HIV V82A 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. V82T 2005 Journal of the International AIDS Society Table HIV V82T 0 4 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Y181C 2005 Journal of the International AIDS Society Table HIV Y181C 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Y188C 2005 Journal of the International AIDS Society Table HIV Y188C 0 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Y188H/L 2005 Journal of the International AIDS Society Table HIV Y188H;Y188L 0;0 7;7 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Y188L 2005 Journal of the International AIDS Society Table HIV Y188L 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. A98G 2008 Future HIV therapy Table HIV A98G 0 4 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. E138A 2008 Future HIV therapy Table HIV E138A 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. G190A 2008 Future HIV therapy Table HIV G190A 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. G190S 2008 Future HIV therapy Table HIV G190S 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. K101E 2008 Future HIV therapy Table HIV K101E 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. K101H 2008 Future HIV therapy Table HIV K101H 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. K101P 2008 Future HIV therapy Table HIV K101P 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. L100I 2008 Future HIV therapy Table HIV L100I 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. M230L 2008 Future HIV therapy Table HIV M230L 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. V106I 2008 Future HIV therapy Table HIV V106I 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. V179D 2008 Future HIV therapy Table HIV V179D 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. V179F 2008 Future HIV therapy Table HIV V179F 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. V179T 2008 Future HIV therapy Table HIV V179T 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. V90I 2008 Future HIV therapy Table HIV V90I 0 4 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Y181C 2008 Future HIV therapy Table HIV Y181C 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Y181I 2008 Future HIV therapy Table HIV Y181I 0 5 19881888 Etravirine: a second-generation NNRTI for treatment-experienced adults with resistant HIV-1 infection. Y181V 2008 Future HIV therapy Table HIV Y181V 0 5 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. G86A 2010 Proteins Table HIV G86A 0 4 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. G86S 2010 Proteins Table HIV G86S 0 4 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. D67N 2009 Clinical infectious diseases Table HIV D67N 0 4 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. F227L 2009 Clinical infectious diseases Table HIV F227L 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. G190A 2009 Clinical infectious diseases Table HIV G190A 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. K103N 2009 Clinical infectious diseases Table HIV K103N 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. K70R 2009 Clinical infectious diseases Table HIV K70R 0 4 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. L74V 2009 Clinical infectious diseases Table HIV L74V 0 4 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. M184V/I 2009 Clinical infectious diseases Table HIV M184I;M184V 0;0 7;7 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. M230L 2009 Clinical infectious diseases Table HIV M230L 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. P225H 2009 Clinical infectious diseases Table HIV P225H 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. V106M 2009 Clinical infectious diseases Table HIV V106M 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. V108I 2009 Clinical infectious diseases Table HIV V108I 0 5 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Y188L 2009 Clinical infectious diseases Table HIV Y188L 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. A62T 2010 The Journal of antimicrobial chemotherapy Table HIV A62T 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. A62V 2010 The Journal of antimicrobial chemotherapy Table HIV A62V 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. D67D/N 2010 The Journal of antimicrobial chemotherapy Table HIV D67D;D67N 0;0 6;6 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. D67G 2010 The Journal of antimicrobial chemotherapy Table HIV D67G 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. D67N 2010 The Journal of antimicrobial chemotherapy Table HIV D67N 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. F77L 2010 The Journal of antimicrobial chemotherapy Table HIV F77L 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. G190E 2010 The Journal of antimicrobial chemotherapy Table HIV G190E 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K103K/N 2010 The Journal of antimicrobial chemotherapy Table HIV K103K;K103N 0;0 7;7 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K103N 2010 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K103R 2010 The Journal of antimicrobial chemotherapy Table HIV K103R 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K219E 2010 The Journal of antimicrobial chemotherapy Table HIV K219E 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K219Q 2010 The Journal of antimicrobial chemotherapy Table HIV K219Q 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K219T 2010 The Journal of antimicrobial chemotherapy Table HIV K219T 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K65K/R 2010 The Journal of antimicrobial chemotherapy Table HIV K65K;K65R 0;0 6;6 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K65R 2010 The Journal of antimicrobial chemotherapy Table HIV K65R 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K70E 2010 The Journal of antimicrobial chemotherapy Table HIV K70E 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K70K/R 2010 The Journal of antimicrobial chemotherapy Table HIV K70K;K70R 0;0 6;6 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K70R 2010 The Journal of antimicrobial chemotherapy Table HIV K70R 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K70T 2010 The Journal of antimicrobial chemotherapy Table HIV K70T 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. L210L/W 2010 The Journal of antimicrobial chemotherapy Table HIV L210L;L210W 0;0 7;7 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. L210W 2010 The Journal of antimicrobial chemotherapy Table HIV L210W 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. M184I 2010 The Journal of antimicrobial chemotherapy Table HIV M184I 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. M184V 2010 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. M41I 2010 The Journal of antimicrobial chemotherapy Table HIV M41I 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. M41L 2010 The Journal of antimicrobial chemotherapy Table HIV M41L 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. M41V 2010 The Journal of antimicrobial chemotherapy Table HIV M41V 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. S68G 2010 The Journal of antimicrobial chemotherapy Table HIV S68G 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. S68N 2010 The Journal of antimicrobial chemotherapy Table HIV S68N 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. T215A 2010 The Journal of antimicrobial chemotherapy Table HIV T215A 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. T215F 2010 The Journal of antimicrobial chemotherapy Table HIV T215F 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. T215L 2010 The Journal of antimicrobial chemotherapy Table HIV T215L 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. T215S 2010 The Journal of antimicrobial chemotherapy Table HIV T215S 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. T215T/A 2010 The Journal of antimicrobial chemotherapy Table HIV T215A;T215T 0;0 7;7 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. T215Y 2010 The Journal of antimicrobial chemotherapy Table HIV T215Y 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. V118I 2010 The Journal of antimicrobial chemotherapy Table HIV V118I 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Y115F 2010 The Journal of antimicrobial chemotherapy Table HIV Y115F 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Y115F/Y 2010 The Journal of antimicrobial chemotherapy Table HIV Y115F;Y115Y 0;0 7;7 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Y181H 2010 The Journal of antimicrobial chemotherapy Table HIV Y181H 0 5 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Y188F/H 2010 The Journal of antimicrobial chemotherapy Table HIV Y188F;Y188H 0;0 7;7 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Y188L 2010 The Journal of antimicrobial chemotherapy Table HIV Y188L 0 5 20010074 N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. N348I 2010 AIDS (London, England) Table HIV N348I 0 5 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. Q151M 2009 AIDS research and therapy Table HIV Q151M 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. G190A 2010 The Journal of infectious diseases Table HIV G190A 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. G190A/S 2010 The Journal of infectious diseases Table HIV G190A;G190S 0;0 7;7 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. G190E 2010 The Journal of infectious diseases Table HIV G190E 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. G190S 2010 The Journal of infectious diseases Table HIV G190S 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. K101E 2010 The Journal of infectious diseases Table HIV K101E 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. K103N 2010 The Journal of infectious diseases Table HIV K103N 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. L100I 2010 The Journal of infectious diseases Table HIV L100I 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. P225H 2010 The Journal of infectious diseases Table HIV P225H 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. V106M 2010 The Journal of infectious diseases Table HIV V106M 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. V108I 2010 The Journal of infectious diseases Table HIV V108I 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. Y181C 2010 The Journal of infectious diseases Table HIV Y181C 0 5 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. Y188H/L 2010 The Journal of infectious diseases Table HIV Y188H;Y188L 0;0 7;7 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. Y188L 2010 The Journal of infectious diseases Table HIV Y188L 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. E438N 2010 Retrovirology Table HIV E438N 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. F440A 2010 Retrovirology Table HIV F440A 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. F440V 2010 Retrovirology Table HIV F440V 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. F440W 2010 Retrovirology Table HIV F440W 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. T439S 2010 Retrovirology Table HIV T439S 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. T477A 2010 Retrovirology Table HIV T477A 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. V442G 2010 Retrovirology Table HIV V442G 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. V442K 2010 Retrovirology Table HIV V442K 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Y441A 2010 Retrovirology Table HIV Y441A 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Y441I 2010 Retrovirology Table HIV Y441I 0 5 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Y441W 2010 Retrovirology Table HIV Y441W 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. D67N 2010 Clinical infectious diseases Table HIV D67N 0 4 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. G190A 2010 Clinical infectious diseases Table HIV G190A 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. G190S 2010 Clinical infectious diseases Table HIV G190S 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. K101E 2010 Clinical infectious diseases Table HIV K101E 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. K103N 2010 Clinical infectious diseases Table HIV K103N 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. K70R 2010 Clinical infectious diseases Table HIV K70R 0 4 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. M41L 2010 Clinical infectious diseases Table HIV M41L 0 4 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. T69N 2010 Clinical infectious diseases Table HIV T69N 0 4 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. V106A 2010 Clinical infectious diseases Table HIV V106A 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. V106I 2010 Clinical infectious diseases Table HIV V106I 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. V179D 2010 Clinical infectious diseases Table HIV V179D 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. V90I 2010 Clinical infectious diseases Table HIV V90I 0 4 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. Y181C 2010 Clinical infectious diseases Table HIV Y181C 0 5 20158398 Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. Y188C 2010 Clinical infectious diseases Table HIV Y188C 0 5 20174661 HIV drug resistance surveillance using pooled pyrosequencing. A71T 2010 PloS one Table HIV A71T 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. A71V 2010 PloS one Table HIV A71V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. D30N 2010 PloS one Table HIV D30N 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. D60E 2010 PloS one Table HIV D60E 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. F53L 2010 PloS one Table HIV F53L 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. G16E 2010 PloS one Table HIV G16E 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. G73S 2010 PloS one Table HIV G73S 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. H69K 2010 PloS one Table HIV H69K 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I47V 2010 PloS one Table HIV I47V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I50V 2010 PloS one Table HIV I50V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I54T 2010 PloS one Table HIV I54T 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I62V 2010 PloS one Table HIV I62V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I64L 2010 PloS one Table HIV I64L 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I64M 2010 PloS one Table HIV I64M 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I64V 2010 PloS one Table HIV I64V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I84V 2010 PloS one Table HIV I84V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I85V 2010 PloS one Table HIV I85V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. I93L 2010 PloS one Table HIV I93L 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. K20I 2010 PloS one Table HIV K20I 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. K20R 2010 PloS one Table HIV K20R 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. L10V 2010 PloS one Table HIV L10V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. L33I 2010 PloS one Table HIV L33I 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. L33V 2010 PloS one Table HIV L33V 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. M36I 2010 PloS one Table HIV M36I 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. M46I 2010 PloS one Table HIV M46I 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. M46L 2010 PloS one Table HIV M46L 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. N88D 2010 PloS one Table HIV N88D 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. N88S 2010 PloS one Table HIV N88S 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. V77I 2010 PloS one Table HIV V77I 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. V82A 2010 PloS one Table HIV V82A 0 4 20174661 HIV drug resistance surveillance using pooled pyrosequencing. V82I 2010 PloS one Table HIV V82I 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. G36D 2010 Biochemistry Table HIV G36D 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. G36E 2010 Biochemistry Table HIV G36E 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. G36S 2010 Biochemistry Table HIV G36S 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. G36V 2010 Biochemistry Table HIV G36V 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. I37K 2010 Biochemistry Table HIV I37K 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. I37T 2010 Biochemistry Table HIV I37T 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. L33Q 2010 Biochemistry Table HIV L33Q 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. L33S 2010 Biochemistry Table HIV L33S 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. N42T 2010 Biochemistry Table HIV N42T 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. N43D 2010 Biochemistry Table HIV N43D 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Q40H 2010 Biochemistry Table HIV Q40H 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Q40K 2010 Biochemistry Table HIV Q40K 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Q41R 2010 Biochemistry Table HIV Q41R 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. V38A 2010 Biochemistry Table HIV V38A 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. V38E 2010 Biochemistry Table HIV V38E 0 4 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. V38M 2010 Biochemistry Table HIV V38M 0 4 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. A179I 2010 Virology journal Table HIV A179I 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. A179P 2010 Virology journal Table HIV A179P 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. F185A 2010 Virology journal Table HIV F185A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. H171A 2010 Virology journal Table HIV H171A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. I182A 2010 Virology journal Table HIV I182A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. I200A 2010 Virology journal Table HIV I200A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. I203A 2010 Virology journal Table HIV I203A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. I203P 2010 Virology journal Table HIV I203P 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. K136A 2010 Virology journal Table HIV K136A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. K159P 2010 Virology journal Table HIV K159P 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. L172A 2010 Virology journal Table HIV L172A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. V165A 2010 Virology journal Table HIV V165A 0 5 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. V176A 2010 Virology journal Table HIV V176A 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. A288S 2010 Virology Table HIV A288S 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. A371T 2010 Virology Table HIV A371T 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. A376T 2010 Virology Table HIV A376T 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. A400T 2010 Virology Table HIV A400T 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. C162S 2010 Virology Table HIV C162S 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. D460N 2010 Virology Table HIV D460N 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. E298K 2010 Virology Table HIV E298K 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. E399D 2010 Virology Table HIV E399D 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. G190S 2010 Virology Table HIV G190S 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. I142V 2010 Virology Table HIV I142V 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. I435V 2010 Virology Table HIV I435V 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K101E 2010 Virology Table HIV K101E 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K102Q 2010 Virology Table HIV K102Q 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K358R 2010 Virology Table HIV K358R 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. K43N 2010 Virology Table HIV K43N 0 4 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. L491S 2010 Virology Table HIV L491S 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. L74V 2010 Virology Table HIV L74V 0 4 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. M41L 2010 Virology Table HIV M41L 0 4 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. P468S 2010 Virology Table HIV P468S 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Q174K 2010 Virology Table HIV Q174K 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Q207N 2010 Virology Table HIV Q207N 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Q258L 2010 Virology Table HIV Q258L 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Q480E 2010 Virology Table HIV Q480E 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. R211K 2010 Virology Table HIV R211K 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. R277K 2010 Virology Table HIV R277K 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. R461K 2010 Virology Table HIV R461K 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. T215Y 2010 Virology Table HIV T215Y 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. T27S 2010 Virology Table HIV T27S 0 4 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. T286A 2010 Virology Table HIV T286A 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. T386I 2010 Virology Table HIV T386I 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. T403S 2010 Virology Table HIV T403S 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. V293I 2010 Virology Table HIV V293I 0 5 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. V467I 2010 Virology Table HIV V467I 0 5 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. G163G/R 2010 PloS one Table HIV G163G;G163R 0;0 7;7 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. I203M 2010 PloS one Table HIV I203M 0 5 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. L74L/M 2010 PloS one Table HIV L74L;L74M 0;0 6;6 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. N155N/H 2010 PloS one Table HIV N155H;N155N 0;0 7;7 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. T97A/T 2010 PloS one Table HIV T97A;T97T 0;0 6;6 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. V151I/V 2010 PloS one Table HIV V151I;V151V 0;0 7;7 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. V201I/V 2010 PloS one Table HIV V201I;V201V 0;0 7;7 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. V72I 2010 PloS one Table HIV V72I 0 4 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Y143C 2010 PloS one Table HIV Y143C 0 5 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Y143C/H 2010 PloS one Table HIV Y143C;Y143H 0;0 7;7 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Y143C/Y 2010 PloS one Table HIV Y143C;Y143Y 0;0 7;7 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Y143Y/C 2010 PloS one Table HIV Y143C;Y143Y 0;0 7;7 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. A98G 2010 The Journal of antimicrobial chemotherapy Table HIV A98G 0 4 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. F227L 2010 The Journal of antimicrobial chemotherapy Table HIV F227L 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. G190A 2010 The Journal of antimicrobial chemotherapy Table HIV G190A 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. G190S 2010 The Journal of antimicrobial chemotherapy Table HIV G190S 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. H221Y 2010 The Journal of antimicrobial chemotherapy Table HIV H221Y 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K101E 2010 The Journal of antimicrobial chemotherapy Table HIV K101E 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K101H 2010 The Journal of antimicrobial chemotherapy Table HIV K101H 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K101P 2010 The Journal of antimicrobial chemotherapy Table HIV K101P 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K102N 2010 The Journal of antimicrobial chemotherapy Table HIV K102N 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K103N 2010 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K103S 2010 The Journal of antimicrobial chemotherapy Table HIV K103S 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. K238T 2010 The Journal of antimicrobial chemotherapy Table HIV K238T 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. L100I 2010 The Journal of antimicrobial chemotherapy Table HIV L100I 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. P225H 2010 The Journal of antimicrobial chemotherapy Table HIV P225H 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. V106A 2010 The Journal of antimicrobial chemotherapy Table HIV V106A 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. V106I 2010 The Journal of antimicrobial chemotherapy Table HIV V106I 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. V106M 2010 The Journal of antimicrobial chemotherapy Table HIV V106M 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. V108I 2010 The Journal of antimicrobial chemotherapy Table HIV V108I 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. V179D 2010 The Journal of antimicrobial chemotherapy Table HIV V179D 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. V179F 2010 The Journal of antimicrobial chemotherapy Table HIV V179F 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Y181C 2010 The Journal of antimicrobial chemotherapy Table HIV Y181C 0 5 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Y188L 2010 The Journal of antimicrobial chemotherapy Table HIV Y188L 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. A71T 2010 PloS one Table HIV A71T 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. D60E 2010 PloS one Table HIV D60E 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. D67G 2010 PloS one Table HIV D67G 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. D67N 2010 PloS one Table HIV D67N 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. G190A 2010 PloS one Table HIV G190A 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. H69K 2010 PloS one Table HIV H69K 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. I13V 2010 PloS one Table HIV I13V 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. I62V 2010 PloS one Table HIV I62V 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. I64L 2010 PloS one Table HIV I64L 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. I64V 2010 PloS one Table HIV I64V 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. I84V 2010 PloS one Table HIV I84V 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. I85V 2010 PloS one Table HIV I85V 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. I93L 2010 PloS one Table HIV I93L 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K103N 2010 PloS one Table HIV K103N 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K103R 2010 PloS one Table HIV K103R 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K20M 2010 PloS one Table HIV K20M 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K20R 2010 PloS one Table HIV K20R 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K20V 2010 PloS one Table HIV K20V 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K219N 2010 PloS one Table HIV K219N 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K219Q 2010 PloS one Table HIV K219Q 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K43T 2010 PloS one Table HIV K43T 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K65R 2010 PloS one Table HIV K65R 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. K70R 2010 PloS one Table HIV K70R 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. L10F 2010 PloS one Table HIV L10F 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. L10I 2010 PloS one Table HIV L10I 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. L10R 2010 PloS one Table HIV L10R 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. L210W 2010 PloS one Table HIV L210W 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. L63P 2010 PloS one Table HIV L63P 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. L90M 2010 PloS one Table HIV L90M 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. M184I 2010 PloS one Table HIV M184I 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. M184V 2010 PloS one Table HIV M184V 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. M184V/I 2010 PloS one Table HIV M184I;M184V 0;0 7;7 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. M36I 2010 PloS one Table HIV M36I 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. M41L 2010 PloS one Table HIV M41L 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. M46I 2010 PloS one Table HIV M46I 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Q58E 2010 PloS one Table HIV Q58E 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. T215C 2010 PloS one Table HIV T215C 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. T215F 2010 PloS one Table HIV T215F 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. T215Y 2010 PloS one Table HIV T215Y 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. V179D 2010 PloS one Table HIV V179D 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. V32I 2010 PloS one Table HIV V32I 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. V75A 2010 PloS one Table HIV V75A 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. V77I 2010 PloS one Table HIV V77I 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. V82I 2010 PloS one Table HIV V82I 0 4 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Y118I 2010 PloS one Table HIV Y118I 0 5 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. Y181C 2010 PloS one Table HIV Y181C 0 5 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. K103N 2010 Letters in drug design & discovery Table HIV K103N 0 5 20535242 Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs. Y181C 2010 Letters in drug design & discovery Table HIV Y181C 0 5 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. K65A 2010 Journal of molecular biology Table HIV K65A 0 4 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. K65R 2010 Journal of molecular biology Table HIV K65R 0 4 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. K65K 2010 PloS one Table HIV K65K 0 4 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. K65R 2010 PloS one Table HIV K65R 0 4 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. K101E 2010 Bioorganic & medicinal chemistry letters Table HIV K101E 0 5 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. L74V 2010 Bioorganic & medicinal chemistry letters Table HIV L74V 0 4 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. M41L 2010 Bioorganic & medicinal chemistry letters Table HIV M41L 0 4 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. T215Y 2010 Bioorganic & medicinal chemistry letters Table HIV T215Y 0 5 20542430 Synthesis and anti-HIV activity of 2'-deoxy-2'-fluoro-4'-C-ethynyl nucleoside analogs. V106A 2010 Bioorganic & medicinal chemistry letters Table HIV V106A 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. A196X 2010 PloS one Table HIV A196X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. A54X 2010 PloS one Table HIV A54X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. D295X 2010 PloS one Table HIV D295X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. E203X 2010 PloS one Table HIV E203X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. E479X 2010 PloS one Table HIV E479X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. E480X 2010 PloS one Table HIV E480X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. E93X 2010 PloS one Table HIV E93X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. F79X 2010 PloS one Table HIV F79X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. G248X 2010 PloS one Table HIV G248X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. H480X 2010 PloS one Table HIV H480X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. I104X 2010 PloS one Table HIV I104X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. I223X 2010 PloS one Table HIV I223X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. K18X 2010 PloS one Table HIV K18X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. K76X 2010 PloS one Table HIV K76X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. L483X 2010 PloS one Table HIV L483X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. L75X 2010 PloS one Table HIV L75X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. M186X 2010 PloS one Table HIV M186X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. M228X 2010 PloS one Table HIV M228X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. M463X 2010 PloS one Table HIV M463X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. N315X 2010 PloS one Table HIV N315X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. P255X 2010 PloS one Table HIV P255X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. P451X 2010 PloS one Table HIV P451X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. P453X 2010 PloS one Table HIV P453X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. P482X 2010 PloS one Table HIV P482X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. P483X 2010 PloS one Table HIV P483X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Q473X 2010 PloS one Table HIV Q473X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Q476X 2010 PloS one Table HIV Q476X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. R286X 2010 PloS one Table HIV R286X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. R30X 2010 PloS one Table HIV R30X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. R387X 2010 PloS one Table HIV R387X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. R401X 2010 PloS one Table HIV R401X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. R403X 2010 PloS one Table HIV R403X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. S125X 2010 PloS one Table HIV S125X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. S281X 2010 PloS one Table HIV S281X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. S357X 2010 PloS one Table HIV S357X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. S66X 2010 PloS one Table HIV S66X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T242N 2010 PloS one Table HIV T242N 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T242X 2010 PloS one Table HIV T242X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T310X 2010 PloS one Table HIV T310X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T348X 2010 PloS one Table HIV T348X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T454X 2010 PloS one Table HIV T454X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T456X 2010 PloS one Table HIV T456X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T487X 2010 PloS one Table HIV T487X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T53X 2010 PloS one Table HIV T53X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. T81X 2010 PloS one Table HIV T81X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. V280X 2010 PloS one Table HIV V280X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. V35X 2010 PloS one Table HIV V35X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. V485X 2010 PloS one Table HIV V485X 0 5 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. V82X 2010 PloS one Table HIV V82X 0 4 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. V83X 2010 PloS one Table HIV V83X 0 4 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. A64V 2010 The Journal of antimicrobial chemotherapy Table HIV A64V 0 4 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. D67N 2010 The Journal of antimicrobial chemotherapy Table HIV D67N 0 4 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. G190A 2010 The Journal of antimicrobial chemotherapy Table HIV G190A 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. G190S 2010 The Journal of antimicrobial chemotherapy Table HIV G190S 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. K101E 2010 The Journal of antimicrobial chemotherapy Table HIV K101E 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. K103N 2010 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. K219Q 2010 The Journal of antimicrobial chemotherapy Table HIV K219Q 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. K70R 2010 The Journal of antimicrobial chemotherapy Table HIV K70R 0 4 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. L210W 2010 The Journal of antimicrobial chemotherapy Table HIV L210W 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. M184V 2010 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. T215F 2010 The Journal of antimicrobial chemotherapy Table HIV T215F 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. T215Y 2010 The Journal of antimicrobial chemotherapy Table HIV T215Y 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. V108I 2010 The Journal of antimicrobial chemotherapy Table HIV V108I 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. V179T 2010 The Journal of antimicrobial chemotherapy Table HIV V179T 0 5 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. V75I 2010 The Journal of antimicrobial chemotherapy Table HIV V75I 0 4 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. V90I 2010 The Journal of antimicrobial chemotherapy Table HIV V90I 0 4 20576637 Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. Y181C 2010 The Journal of antimicrobial chemotherapy Table HIV Y181C 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. G190A 2010 PloS one Table HIV G190A 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. G190S 2010 PloS one Table HIV G190S 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. K219E 2010 PloS one Table HIV K219E 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. K219Q 2010 PloS one Table HIV K219Q 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. L210W 2010 PloS one Table HIV L210W 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. M184I 2010 PloS one Table HIV M184I 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. M184V 2010 PloS one Table HIV M184V 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215A 2010 PloS one Table HIV T215A 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215C/D 2010 PloS one Table HIV T215C;T215D 0;0 7;7 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215F 2010 PloS one Table HIV T215F 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215G 2010 PloS one Table HIV T215G 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215I 2010 PloS one Table HIV T215I 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215N 2010 PloS one Table HIV T215N 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215S 2010 PloS one Table HIV T215S 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. T215Y 2010 PloS one Table HIV T215Y 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Y181C 2010 PloS one Table HIV Y181C 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Y181I 2010 PloS one Table HIV Y181I 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Y181V 2010 PloS one Table HIV Y181V 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Y188C 2010 PloS one Table HIV Y188C 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Y188H 2010 PloS one Table HIV Y188H 0 5 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Y188L 2010 PloS one Table HIV Y188L 0 5 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. I50V 2010 The FEBS journal Table HIV I50V 0 4 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. I54M 2010 The FEBS journal Table HIV I54M 0 4 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. I54V 2010 The FEBS journal Table HIV I54V 0 4 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. I84V 2010 The FEBS journal Table HIV I84V 0 4 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. L90M 2010 The FEBS journal Table HIV L90M 0 4 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. V32I 2010 The FEBS journal Table HIV V32I 0 4 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. M184I 2010 Virology Table HIV M184I 0 5 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. N155H 2010 Biochemistry Table HIV N155H 0 5 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Q148H 2010 Biochemistry Table HIV Q148H 0 5 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. K95R 2010 PloS one Table HIV K95R 0 4 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. T89A 2010 PloS one Table HIV T89A 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. A33C 2009 Journal of medical case reports Table HIV A33C 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. E35D 2009 Journal of medical case reports Table HIV E35D 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. E36N 2009 Journal of medical case reports Table HIV E36N 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. I15V 2009 Journal of medical case reports Table HIV I15V 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. I37F 2009 Journal of medical case reports Table HIV I37F 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. K103N 2009 Journal of medical case reports Table HIV K103N 0 5 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. K30Q 2009 Journal of medical case reports Table HIV K30Q 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. K64R 2009 Journal of medical case reports Table HIV K64R 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. L10V 2009 Journal of medical case reports Table HIV L10V 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. L34T 2009 Journal of medical case reports Table HIV L34T 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. L63P 2009 Journal of medical case reports Table HIV L63P 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. R211K 2009 Journal of medical case reports Table HIV R211K 0 5 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. R41K 2009 Journal of medical case reports Table HIV R41K 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. R57K 2009 Journal of medical case reports Table HIV R57K 0 4 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. V245Q 2009 Journal of medical case reports Table HIV V245Q 0 5 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. V35L 2009 Journal of medical case reports Table HIV V35L 0 4 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. K70Q 2011 PloS one Table HIV K70Q 0 4 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. K65R 2011 Virology journal Table HIV K65R 0 4 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. L74I 2011 Virology journal Table HIV L74I 0 4 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. L74V 2011 Virology journal Table HIV L74V 0 4 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. E44D 2011 PloS one Table HIV E44D 0 4 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. T69D 2011 PloS one Table HIV T69D 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? A71I 2011 AIDS research and therapy Table HIV A71I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? A71T 2011 AIDS research and therapy Table HIV A71T 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? A71V 2011 AIDS research and therapy Table HIV A71V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? D60E 2011 AIDS research and therapy Table HIV D60E 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? F53L 2011 AIDS research and therapy Table HIV F53L 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? G73S 2011 AIDS research and therapy Table HIV G73S 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? I13V 2011 AIDS research and therapy Table HIV I13V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? I47V 2011 AIDS research and therapy Table HIV I47V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? I50V 2011 AIDS research and therapy Table HIV I50V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? I54M 2011 AIDS research and therapy Table HIV I54M 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? I54V 2011 AIDS research and therapy Table HIV I54V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? I84V 2011 AIDS research and therapy Table HIV I84V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? K20I 2011 AIDS research and therapy Table HIV K20I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? K20R 2011 AIDS research and therapy Table HIV K20R 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L10F 2011 AIDS research and therapy Table HIV L10F 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L10I 2011 AIDS research and therapy Table HIV L10I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L10V 2011 AIDS research and therapy Table HIV L10V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L24I 2011 AIDS research and therapy Table HIV L24I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L33F 2011 AIDS research and therapy Table HIV L33F 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L33I 2011 AIDS research and therapy Table HIV L33I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L63P 2011 AIDS research and therapy Table HIV L63P 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L76V 2011 AIDS research and therapy Table HIV L76V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? L90M 2011 AIDS research and therapy Table HIV L90M 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? M36I 2011 AIDS research and therapy Table HIV M36I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? M46I 2011 AIDS research and therapy Table HIV M46I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? M46L 2011 AIDS research and therapy Table HIV M46L 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? V11I 2011 AIDS research and therapy Table HIV V11I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? V32I 2011 AIDS research and therapy Table HIV V32I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? V76V 2011 AIDS research and therapy Table HIV V76V 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? V77I 2011 AIDS research and therapy Table HIV V77I 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? V82A 2011 AIDS research and therapy Table HIV V82A 0 4 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? V82F 2011 AIDS research and therapy Table HIV V82F 0 4 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. F519L 2011 Virology Table HIV F519L 0 5 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. G514V 2011 Virology Table HIV G514V 0 5 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. H308P 2011 Virology Table HIV H308P 0 5 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. M518V 2011 Virology Table HIV M518V 0 5 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. V535M 2011 Virology Table HIV V535M 0 5 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. D67G 2011 PLoS medicine Table HIV D67G 0 4 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. G190A 2011 PLoS medicine Table HIV G190A 0 5 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. K103N 2011 PLoS medicine Table HIV K103N 0 5 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. K65R 2011 PLoS medicine Table HIV K65R 0 4 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. M184I 2011 PLoS medicine Table HIV M184I 0 5 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. M184I/V 2011 PLoS medicine Table HIV M184I;M184V 0;0 7;7 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. M184V 2011 PLoS medicine Table HIV M184V 0 5 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. V106A 2011 PLoS medicine Table HIV V106A 0 5 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. Y181C 2011 PLoS medicine Table HIV Y181C 0 5 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Q151M 2011 Retrovirology Table HIV Q151M 0 5 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. A189S 2011 Retrovirology Table HIV A189S 0 5 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. A30T 2011 Retrovirology Table HIV A30T 0 4 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. A96N 2011 Retrovirology Table HIV A96N 0 4 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. A96T 2011 Retrovirology Table HIV A96T 0 4 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. L210P 2011 Retrovirology Table HIV L210P 0 5 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. L34M 2011 Retrovirology Table HIV L34M 0 4 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. N195K 2011 Retrovirology Table HIV N195K 0 5 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. S11S 2011 Retrovirology Table HIV S11S 0 4 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. S129N 2011 Retrovirology Table HIV S129N 0 5 21569409 Selected amino acid mutations in HIV-1 B subtype gp41 are associated with specific gp120v(3) signatures in the regulation of co-receptor usage. T22A 2011 Retrovirology Table HIV T22A 0 4 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. K103N 2011 PloS one Table HIV K103N 0 5 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. Y181C 2011 PloS one Table HIV Y181C 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. A98G 2011 Journal of the International AIDS Society Table HIV A98G 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. A98S 2011 Journal of the International AIDS Society Table HIV A98S 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. D67G 2011 Journal of the International AIDS Society Table HIV D67G 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. D67N 2011 Journal of the International AIDS Society Table HIV D67N 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. G190A 2011 Journal of the International AIDS Society Table HIV G190A 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. G190S 2011 Journal of the International AIDS Society Table HIV G190S 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. H221Y 2011 Journal of the International AIDS Society Table HIV H221Y 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. K101E 2011 Journal of the International AIDS Society Table HIV K101E 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. K103N 2011 Journal of the International AIDS Society Table HIV K103N 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. K219E 2011 Journal of the International AIDS Society Table HIV K219E 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. K219Q 2011 Journal of the International AIDS Society Table HIV K219Q 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. K65R 2011 Journal of the International AIDS Society Table HIV K65R 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. K70R 2011 Journal of the International AIDS Society Table HIV K70R 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. L210W 2011 Journal of the International AIDS Society Table HIV L210W 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. M184I 2011 Journal of the International AIDS Society Table HIV M184I 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. M184V 2011 Journal of the International AIDS Society Table HIV M184V 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. M41L 2011 Journal of the International AIDS Society Table HIV M41L 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Q151M 2011 Journal of the International AIDS Society Table HIV Q151M 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. T215F 2011 Journal of the International AIDS Society Table HIV T215F 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. T215Y 2011 Journal of the International AIDS Society Table HIV T215Y 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. T69D 2011 Journal of the International AIDS Society Table HIV T69D 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. T69N 2011 Journal of the International AIDS Society Table HIV T69N 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. T69S 2011 Journal of the International AIDS Society Table HIV T69S 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. V106A 2011 Journal of the International AIDS Society Table HIV V106A 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. V106M 2011 Journal of the International AIDS Society Table HIV V106M 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. V90I 2011 Journal of the International AIDS Society Table HIV V90I 0 4 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Y181C 2011 Journal of the International AIDS Society Table HIV Y181C 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Y181V 2011 Journal of the International AIDS Society Table HIV Y181V 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Y188C 2011 Journal of the International AIDS Society Table HIV Y188C 0 5 21663632 High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. Y188L 2011 Journal of the International AIDS Society Table HIV Y188L 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. D67X 2011 PloS one Table HIV D67X 0 4 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. G190X 2011 PloS one Table HIV G190X 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. I54X 2011 PloS one Table HIV I54X 0 4 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. K103X 2011 PloS one Table HIV K103X 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. K219X 2011 PloS one Table HIV K219X 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. L210X 2011 PloS one Table HIV L210X 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. L90X 2011 PloS one Table HIV L90X 0 4 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. M184X 2011 PloS one Table HIV M184X 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. M41X 2011 PloS one Table HIV M41X 0 4 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. M46X 2011 PloS one Table HIV M46X 0 4 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. T215X 2011 PloS one Table HIV T215X 0 5 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Y181X 2011 PloS one Table HIV Y181X 0 5 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. K103N 2011 PloS one Table HIV K103N 0 5 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. K103N 2011 PloS one Table HIV K103N 0 5 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. M184V 2011 PloS one Table HIV M184V 0 5 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. G190A/Q 2011 PloS one Table HIV G190A;G190Q 0;0 7;7 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. K103N 2011 PloS one Table HIV K103N 0 5 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. K238N 2011 PloS one Table HIV K238N 0 5 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. M184V/I 2011 PloS one Table HIV M184I;M184V 0;0 7;7 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Y181C/I 2011 PloS one Table HIV Y181C;Y181I 0;0 7;7 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Y188L 2011 PloS one Table HIV Y188L 0 5 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. A364V 2011 Retrovirology Table HIV A364V 0 5 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. S368N 2011 Retrovirology Table HIV S368N 0 5 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. V362I 2011 Retrovirology Table HIV V362I 0 5 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. V370A 2011 Retrovirology Table HIV V370A 0 5 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. A98G 2011 Virology journal Table HIV A98G 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. E138A 2011 Virology journal Table HIV E138A 0 5 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. K103N 2011 Virology journal Table HIV K103N 0 5 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. K20I 2011 Virology journal Table HIV K20I 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. K20R 2011 Virology journal Table HIV K20R 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. K70R 2011 Virology journal Table HIV K70R 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. L100I 2011 Virology journal Table HIV L100I 0 5 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. L10V 2011 Virology journal Table HIV L10V 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. L63P 2011 Virology journal Table HIV L63P 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. L90M 2011 Virology journal Table HIV L90M 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. M36I 2011 Virology journal Table HIV M36I 0 4 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. V118I 2011 Virology journal Table HIV V118I 0 5 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. V77I 2011 Virology journal Table HIV V77I 0 4 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. G190A 2011 Bioorganic & medicinal chemistry Table HIV G190A 0 5 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. K103N 2011 Bioorganic & medicinal chemistry Table HIV K103N 0 5 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. L100I 2011 Bioorganic & medicinal chemistry Table HIV L100I 0 5 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. V106A 2011 Bioorganic & medicinal chemistry Table HIV V106A 0 5 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Y181C 2011 Bioorganic & medicinal chemistry Table HIV Y181C 0 5 21903401 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Y188L 2011 Bioorganic & medicinal chemistry Table HIV Y188L 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. I197M 2011 PloS one Table HIV I197M 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K201E 2011 PloS one Table HIV K201E 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K201I 2011 PloS one Table HIV K201I 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K201N 2011 PloS one Table HIV K201N 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K208E 2011 PloS one Table HIV K208E 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K208G 2011 PloS one Table HIV K208G 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K208I 2011 PloS one Table HIV K208I 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K208N 2011 PloS one Table HIV K208N 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. K208R 2011 PloS one Table HIV K208R 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. N161H 2011 PloS one Table HIV N161H 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. Q211R 2011 PloS one Table HIV Q211R 0 5 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. Y154H 2011 PloS one Table HIV Y154H 0 5 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. A71T 2011 PloS one Table HIV A71T 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. A71V 2011 PloS one Table HIV A71V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. D60E 2011 PloS one Table HIV D60E 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. E35D 2011 PloS one Table HIV E35D 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. G16E 2011 PloS one Table HIV G16E 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. H69K 2011 PloS one Table HIV H69K 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I13V 2011 PloS one Table HIV I13V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I15V 2011 PloS one Table HIV I15V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I47A 2011 PloS one Table HIV I47A 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I47V 2011 PloS one Table HIV I47V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I54V 2011 PloS one Table HIV I54V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I62V 2011 PloS one Table HIV I62V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I64V 2011 PloS one Table HIV I64V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. I84V 2011 PloS one Table HIV I84V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. K20I 2011 PloS one Table HIV K20I 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. K20R 2011 PloS one Table HIV K20R 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. L10I 2011 PloS one Table HIV L10I 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. L63P 2011 PloS one Table HIV L63P 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. L76V 2011 PloS one Table HIV L76V 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. L90M 2011 PloS one Table HIV L90M 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. M36I 2011 PloS one Table HIV M36I 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. M46I 2011 PloS one Table HIV M46I 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V32I 2011 PloS one Table HIV V32I 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V77I 2011 PloS one Table HIV V77I 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V82A 2011 PloS one Table HIV V82A 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V82F 2011 PloS one Table HIV V82F 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V82S 2011 PloS one Table HIV V82S 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V82T 2011 PloS one Table HIV V82T 0 4 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V91S 2011 PloS one Table HIV V91S 0 4 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. C125S 2011 PloS one Table HIV C125S 0 5 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. C23S 2011 PloS one Table HIV C23S 0 4 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. D64C 2011 PloS one Table HIV D64C 0 4 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. E157C 2011 PloS one Table HIV E157C 0 5 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. F199K 2011 PloS one Table HIV F199K 0 5 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. I146C 2011 PloS one Table HIV I146C 0 5 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. R244C 2011 PloS one Table HIV R244C 0 5 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. S124C 2011 PloS one Table HIV S124C 0 5 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. W259A 2011 PloS one Table HIV W259A 0 5 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. R76Q 2011 BMC structural biology Table HIV R76Q 0 4 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. R80A 2011 BMC structural biology Table HIV R80A 0 4 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. T84I 2011 BMC structural biology Table HIV T84I 0 4 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. V83I 2011 BMC structural biology Table HIV V83I 0 4 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. N140I 2012 Retrovirology Table HIV N140I 0 5 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. N140T 2012 Retrovirology Table HIV N140T 0 5 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. V38A 2012 Retrovirology Table HIV V38A 0 4 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. F227L 2012 PloS one Table HIV F227L 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. K103N 2012 PloS one Table HIV K103N 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. K65R 2012 PloS one Table HIV K65R 0 4 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. K70E 2012 PloS one Table HIV K70E 0 4 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. L100I 2012 PloS one Table HIV L100I 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. L74V 2012 PloS one Table HIV L74V 0 4 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. M184I 2012 PloS one Table HIV M184I 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. M184V 2012 PloS one Table HIV M184V 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. M41L 2012 PloS one Table HIV M41L 0 4 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. P225H 2012 PloS one Table HIV P225H 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. T215D 2012 PloS one Table HIV T215D 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. T215N 2012 PloS one Table HIV T215N 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. T215S 2012 PloS one Table HIV T215S 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. T215Y 2012 PloS one Table HIV T215Y 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. V106A 2012 PloS one Table HIV V106A 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. V179E 2012 PloS one Table HIV V179E 0 5 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. Y181C 2012 PloS one Table HIV Y181C 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A360A/V 2012 PloS one Table HIV A360A;A360V 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A360V 2012 PloS one Table HIV A360V 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A371V 2012 PloS one Table HIV A371V 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A446S 2012 PloS one Table HIV A446S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A554A 2012 PloS one Table HIV A554A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A554A/S 2012 PloS one Table HIV A554A;A554S 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. A554T 2012 PloS one Table HIV A554T 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. D123D/E 2012 PloS one Table HIV D123D;D123E 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. D123E 2012 PloS one Table HIV D123E 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. D177E 2012 PloS one Table HIV D177E 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. D460N 2012 PloS one Table HIV D460N 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. D67D/N 2012 PloS one Table HIV D67D;D67N 0;0 6;6 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. D67N 2012 PloS one Table HIV D67N 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E122K 2012 PloS one Table HIV E122K 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E291D 2012 PloS one Table HIV E291D 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E297K 2012 PloS one Table HIV E297K 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E312A 2012 PloS one Table HIV E312A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E328D 2012 PloS one Table HIV E328D 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E399D 2012 PloS one Table HIV E399D 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E404D 2012 PloS one Table HIV E404D 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. E42E/K 2012 PloS one Table HIV E42E;E42K 0;0 6;6 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. F346F/H 2012 PloS one Table HIV F346F;F346H 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. G333E 2012 PloS one Table HIV G333E 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. G359S 2012 PloS one Table HIV G359S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. I178I/L 2012 PloS one Table HIV I178I;I178L 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. I293V 2012 PloS one Table HIV I293V 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. I329L 2012 PloS one Table HIV I329L 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. I329V 2012 PloS one Table HIV I329V 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K103K/R 2012 PloS one Table HIV K103K;K103R 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K104K/N 2012 PloS one Table HIV K104K;K104N 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K20K 2012 PloS one Table HIV K20K 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K219E 2012 PloS one Table HIV K219E 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K219E/K 2012 PloS one Table HIV K219E;K219K 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K219E/Q 2012 PloS one Table HIV K219E;K219Q 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K219K/Q 2012 PloS one Table HIV K219K;K219Q 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K263R 2012 PloS one Table HIV K263R 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K275R 2012 PloS one Table HIV K275R 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K281R 2012 PloS one Table HIV K281R 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K311K/R 2012 PloS one Table HIV K311K;K311R 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K390R 2012 PloS one Table HIV K390R 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K451K/R 2012 PloS one Table HIV K451K;K451R 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K451R 2012 PloS one Table HIV K451R 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K512R 2012 PloS one Table HIV K512R 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K527N 2012 PloS one Table HIV K527N 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K530K/R 2012 PloS one Table HIV K530K;K530R 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K540K/R 2012 PloS one Table HIV K540K;K540R 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K70K/R 2012 PloS one Table HIV K70K;K70R 0;0 6;6 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. K70R 2012 PloS one Table HIV K70R 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. L210L/W 2012 PloS one Table HIV L210L;L210W 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. L210W 2012 PloS one Table HIV L210W 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. L214F 2012 PloS one Table HIV L214F 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. L282L/P 2012 PloS one Table HIV L282L;L282P 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. L452E/L 2012 PloS one Table HIV L452E;L452L 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. L452L/V 2012 PloS one Table HIV L452L;L452V 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. L491S 2012 PloS one Table HIV L491S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. M41L 2012 PloS one Table HIV M41L 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. N460D 2012 PloS one Table HIV N460D 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. N519C/S 2012 PloS one Table HIV N519C;N519S 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. N519N/S 2012 PloS one Table HIV N519N;N519S 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. N519S 2012 PloS one Table HIV N519S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. N519T 2012 PloS one Table HIV N519T 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. P272A 2012 PloS one Table HIV P272A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Q174K 2012 PloS one Table HIV Q174K 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Q207E 2012 PloS one Table HIV Q207E 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Q278H 2012 PloS one Table HIV Q278H 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Q334H 2012 PloS one Table HIV Q334H 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Q334L 2012 PloS one Table HIV Q334L 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Q394P/Q 2012 PloS one Table HIV Q394P;Q394Q 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. R211K 2012 PloS one Table HIV R211K 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. R277K 2012 PloS one Table HIV R277K 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. R356K 2012 PloS one Table HIV R356K 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. R83K 2012 PloS one Table HIV R83K 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. S162C/Y 2012 PloS one Table HIV S162C;S162Y 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. S447N 2012 PloS one Table HIV S447N 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T200A 2012 PloS one Table HIV T200A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T215I 2012 PloS one Table HIV T215I 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T215I/T 2012 PloS one Table HIV T215I;T215T 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T215S 2012 PloS one Table HIV T215S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T215Y 2012 PloS one Table HIV T215Y 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T253A 2012 PloS one Table HIV T253A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T286A 2012 PloS one Table HIV T286A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T338S 2012 PloS one Table HIV T338S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T357M 2012 PloS one Table HIV T357M 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T376A 2012 PloS one Table HIV T376A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T376S 2012 PloS one Table HIV T376S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T377S 2012 PloS one Table HIV T377S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T39A 2012 PloS one Table HIV T39A 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T400A 2012 PloS one Table HIV T400A 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T400I/T 2012 PloS one Table HIV T400I;T400T 0;0 7;7 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T468P 2012 PloS one Table HIV T468P 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T468S 2012 PloS one Table HIV T468S 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. T69S 2012 PloS one Table HIV T69S 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V245E 2012 PloS one Table HIV V245E 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V245K 2012 PloS one Table HIV V245K 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V245M 2012 PloS one Table HIV V245M 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V292I 2012 PloS one Table HIV V292I 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V35I 2012 PloS one Table HIV V35I 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V35I/V 2012 PloS one Table HIV V35I;V35V 0;0 6;6 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V35L 2012 PloS one Table HIV V35L 0 4 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V365I 2012 PloS one Table HIV V365I 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V381I 2012 PloS one Table HIV V381I 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V435I 2012 PloS one Table HIV V435I 0 5 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. V559I/V 2012 PloS one Table HIV V559I;V559V 0;0 7;7 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. G190A 2012 PloS one Table HIV G190A 0 5 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. K103N 2012 PloS one Table HIV K103N 0 5 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. K65R 2012 PloS one Table HIV K65R 0 4 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. K70R 2012 PloS one Table HIV K70R 0 4 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. M184V 2012 PloS one Table HIV M184V 0 5 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. T215F 2012 PloS one Table HIV T215F 0 5 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. T215Y 2012 PloS one Table HIV T215Y 0 5 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. T215Y/F 2012 PloS one Table HIV T215F;T215Y 0;0 7;7 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Y181C 2012 PloS one Table HIV Y181C 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. D67G 2012 PloS one Table HIV D67G 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. D67N 2012 PloS one Table HIV D67N 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. F116Y 2012 PloS one Table HIV F116Y 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. F77L 2012 PloS one Table HIV F77L 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. G190A 2012 PloS one Table HIV G190A 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. I50V 2012 PloS one Table HIV I50V 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. I54V 2012 PloS one Table HIV I54V 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. I85V 2012 PloS one Table HIV I85V 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. K101E 2012 PloS one Table HIV K101E 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. K103N 2012 PloS one Table HIV K103N 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. K219Q 2012 PloS one Table HIV K219Q 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. K70R 2012 PloS one Table HIV K70R 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. L210W 2012 PloS one Table HIV L210W 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. L24I 2012 PloS one Table HIV L24I 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. M184I 2012 PloS one Table HIV M184I 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. M41L 2012 PloS one Table HIV M41L 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. M46I 2012 PloS one Table HIV M46I 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. M46L 2012 PloS one Table HIV M46L 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. P225H 2012 PloS one Table HIV P225H 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. Q151M 2012 PloS one Table HIV Q151M 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. T215D 2012 PloS one Table HIV T215D 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. T215S 2012 PloS one Table HIV T215S 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. T215Y 2012 PloS one Table HIV T215Y 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. V82A 2012 PloS one Table HIV V82A 0 4 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. Y115F 2012 PloS one Table HIV Y115F 0 5 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. Y181C 2012 PloS one Table HIV Y181C 0 5 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. K103N 2012 PloS one Table HIV K103N 0 5 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. M184V 2012 PloS one Table HIV M184V 0 5 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. V106M 2012 PloS one Table HIV V106M 0 5 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. A437G 2012 Malaria journal Table HIV A437G 0 5 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. A581G 2012 Malaria journal Table HIV A581G 0 5 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. K540E 2012 Malaria journal Table HIV K540E 0 5 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. S436A/F 2012 Malaria journal Table HIV S436A;S436F 0;0 7;7 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. S436H 2012 Malaria journal Table HIV S436H 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. D474D/N 2012 Retrovirology Table HIV D474D;D474N 0;0 7;7 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. D474N 2012 Retrovirology Table HIV D474N 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. G335R 2012 Retrovirology Table HIV G335R 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. G471E 2012 Retrovirology Table HIV G471E 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. G471R 2012 Retrovirology Table HIV G471R 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. H105H/Y 2012 Retrovirology Table HIV H105H;H105Y 0;0 7;7 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. H105Y 2012 Retrovirology Table HIV H105Y 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. L494L/V 2012 Retrovirology Table HIV L494L;L494V 0;0 7;7 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. L494V 2012 Retrovirology Table HIV L494V 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. S375N 2012 Retrovirology Table HIV S375N 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. S375R 2012 Retrovirology Table HIV S375R 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. S375S/N 2012 Retrovirology Table HIV S375N;S375S 0;0 7;7 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. S375S/R 2012 Retrovirology Table HIV S375R;S375S 0;0 7;7 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. V255M 2012 Retrovirology Table HIV V255M 0 5 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K65K 2012 PloS one Table HIV K65K 0 4 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K65R 2012 PloS one Table HIV K65R 0 4 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K70R 2012 PloS one Table HIV K70R 0 4 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. A44L 2012 PloS one Table HIV A44L 0 4 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. F11L 2012 PloS one Table HIV F11L 0 4 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. W61D 2012 Retrovirology Table HIV W61D 0 4 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. K65R 2012 Retrovirology Table HIV K65R 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. A62V 2012 Retrovirology Table HIV A62V 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. A98G 2012 Retrovirology Table HIV A98G 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. D38T 2012 Retrovirology Table HIV D38T 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. D67N 2012 Retrovirology Table HIV D67N 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. E297K 2012 Retrovirology Table HIV E297K 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. G190A 2012 Retrovirology Table HIV G190A 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. G333E 2012 Retrovirology Table HIV G333E 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. H208Y 2012 Retrovirology Table HIV H208Y 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K103N 2012 Retrovirology Table HIV K103N 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K219E 2012 Retrovirology Table HIV K219E 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K219Q 2012 Retrovirology Table HIV K219Q 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K223E 2012 Retrovirology Table HIV K223E 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K65R 2012 Retrovirology Table HIV K65R 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K70R 2012 Retrovirology Table HIV K70R 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. L210W 2012 Retrovirology Table HIV L210W 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. L214F 2012 Retrovirology Table HIV L214F 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. L228H 2012 Retrovirology Table HIV L228H 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. L228R 2012 Retrovirology Table HIV L228R 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. L74I 2012 Retrovirology Table HIV L74I 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. M184V 2012 Retrovirology Table HIV M184V 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. M41L 2012 Retrovirology Table HIV M41L 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Q174R 2012 Retrovirology Table HIV Q174R 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. R284K 2012 Retrovirology Table HIV R284K 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. S162A 2012 Retrovirology Table HIV S162A 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. T215F 2012 Retrovirology Table HIV T215F 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. T215Y 2012 Retrovirology Table HIV T215Y 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. T39A 2012 Retrovirology Table HIV T39A 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. T69N 2012 Retrovirology Table HIV T69N 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. V108I 2012 Retrovirology Table HIV V108I 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. V118I 2012 Retrovirology Table HIV V118I 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. V179I 2012 Retrovirology Table HIV V179I 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. V292I 2012 Retrovirology Table HIV V292I 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. V35I 2012 Retrovirology Table HIV V35I 0 4 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Y181C 2012 Retrovirology Table HIV Y181C 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. A98G 2012 PloS one Table HIV A98G 0 4 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. I135T 2012 PloS one Table HIV I135T 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. I178M 2012 PloS one Table HIV I178M 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. I382L 2012 PloS one Table HIV I382L 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. I382V 2012 PloS one Table HIV I382V 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. K238N 2012 PloS one Table HIV K238N 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. T386A 2012 PloS one Table HIV T386A 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. T48I 2012 PloS one Table HIV T48I 0 4 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. V106M 2012 PloS one Table HIV V106M 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. V108I 2012 PloS one Table HIV V108I 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. V189I 2012 PloS one Table HIV V189I 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. V314A 2012 PloS one Table HIV V314A 0 5 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Y181C 2012 PloS one Table HIV Y181C 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. A153G 2012 PloS one Table HIV A153G 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. A33A 2012 PloS one Table HIV A33A 0 4 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. E92E/A 2012 PloS one Table HIV E92A;E92E 0;0 6;6 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. E92E/Q 2012 PloS one Table HIV E92E;E92Q 0;0 6;6 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. E92G 2012 PloS one Table HIV E92G 0 4 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. E92Q 2012 PloS one Table HIV E92Q 0 4 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. G140S 2012 PloS one Table HIV G140S 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. H157R 2012 PloS one Table HIV H157R 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. H51H/R 2012 PloS one Table HIV H51H;H51R 0;0 6;6 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. I84V 2012 PloS one Table HIV I84V 0 4 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. M183I 2012 PloS one Table HIV M183I 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. N155H 2012 PloS one Table HIV N155H 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. N160K 2012 PloS one Table HIV N160K 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Q148K 2012 PloS one Table HIV Q148K 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Q148K/R 2012 PloS one Table HIV Q148K;Q148R 0;0 7;7 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Q148R 2012 PloS one Table HIV Q148R 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Q91R 2012 PloS one Table HIV Q91R 0 4 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. S147G 2012 PloS one Table HIV S147G 0 5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. S163G/D 2012 PloS one Table HIV S163D;S163G 0;0 7;7 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. S163S/G 2012 PloS one Table HIV S163G;S163S 0;0 7;7 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. T97A 2012 PloS one Table HIV T97A 0 4 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. V72I 2012 PloS one Table HIV V72I 0 4 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Y143H/R 2012 PloS one Table HIV Y143H;Y143R 0;0 7;7 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. A62V 2012 Diagnostic pathology Table HIV A62V 0 4 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. D67N 2012 Diagnostic pathology Table HIV D67N 0 4 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. G190A 2012 Diagnostic pathology Table HIV G190A 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. H221Y 2012 Diagnostic pathology Table HIV H221Y 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. K101E 2012 Diagnostic pathology Table HIV K101E 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. K101Q 2012 Diagnostic pathology Table HIV K101Q 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. K103N 2012 Diagnostic pathology Table HIV K103N 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. K219Q 2012 Diagnostic pathology Table HIV K219Q 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. K219R 2012 Diagnostic pathology Table HIV K219R 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. L10V 2012 Diagnostic pathology Table HIV L10V 0 4 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. L210W 2012 Diagnostic pathology Table HIV L210W 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. L74V 2012 Diagnostic pathology Table HIV L74V 0 4 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. M184V 2012 Diagnostic pathology Table HIV M184V 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. M230L 2012 Diagnostic pathology Table HIV M230L 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. M41L 2012 Diagnostic pathology Table HIV M41L 0 4 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. T215F 2012 Diagnostic pathology Table HIV T215F 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. T215Y 2012 Diagnostic pathology Table HIV T215Y 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. T69N 2012 Diagnostic pathology Table HIV T69N 0 4 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. V179E 2012 Diagnostic pathology Table HIV V179E 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. Y181C 2012 Diagnostic pathology Table HIV Y181C 0 5 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. Y188L 2012 Diagnostic pathology Table HIV Y188L 0 5 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. E138A/K 2012 PloS one Table HIV E138A;E138K 0;0 7;7 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. E92Q 2012 PloS one Table HIV E92Q 0 4 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. G140S 2012 PloS one Table HIV G140S 0 5 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. N155H 2012 PloS one Table HIV N155H 0 5 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Q148H 2012 PloS one Table HIV Q148H 0 5 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Q148H/R 2012 PloS one Table HIV Q148H;Q148R 0;0 7;7 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Q148R 2012 PloS one Table HIV Q148R 0 5 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Y143H/C 2012 PloS one Table HIV Y143C;Y143H 0;0 7;7 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Y143R 2012 PloS one Table HIV Y143R 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. C162S 2012 PloS one Table HIV C162S 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. D121Y 2012 PloS one Table HIV D121Y 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. D123N 2012 PloS one Table HIV D123N 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. D177E 2012 PloS one Table HIV D177E 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. D67D/N 2012 PloS one Table HIV D67D;D67N 0;0 6;6 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. D67N 2012 PloS one Table HIV D67N 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. E169K 2012 PloS one Table HIV E169K 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. E203E 2012 PloS one Table HIV E203E 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. E203E/K 2012 PloS one Table HIV E203E;E203K 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. E203K 2012 PloS one Table HIV E203K 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. E36A 2012 PloS one Table HIV E36A 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. F214F/L 2012 PloS one Table HIV F214F;F214L 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. F214L 2012 PloS one Table HIV F214L 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. I135T 2012 PloS one Table HIV I135T 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. K122E 2012 PloS one Table HIV K122E 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. K173N 2012 PloS one Table HIV K173N 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. K43R 2012 PloS one Table HIV K43R 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. K70K 2012 PloS one Table HIV K70K 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. K70K/R 2012 PloS one Table HIV K70K;K70R 0;0 6;6 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. K70R 2012 PloS one Table HIV K70R 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. M184I 2012 PloS one Table HIV M184I 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. M184M/I 2012 PloS one Table HIV M184I;M184M 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. M184V 2012 PloS one Table HIV M184V 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Q102K 2012 PloS one Table HIV Q102K 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Q102R 2012 PloS one Table HIV Q102R 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Q174K 2012 PloS one Table HIV Q174K 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Q207E 2012 PloS one Table HIV Q207E 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. R211K 2012 PloS one Table HIV R211K 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. S134I 2012 PloS one Table HIV S134I 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. S48T 2012 PloS one Table HIV S48T 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T200A 2012 PloS one Table HIV T200A 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215F 2012 PloS one Table HIV T215F 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215I 2012 PloS one Table HIV T215I 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215I/F 2012 PloS one Table HIV T215F;T215I 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215N/S 2012 PloS one Table HIV T215N;T215S 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215T/I 2012 PloS one Table HIV T215I;T215T 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215T/N 2012 PloS one Table HIV T215N;T215T 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215T/S 2012 PloS one Table HIV T215S;T215T 0;0 7;7 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T215Y 2012 PloS one Table HIV T215Y 0 5 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. T39D 2012 PloS one Table HIV T39D 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. V35T 2012 PloS one Table HIV V35T 0 4 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. V90F 2012 PloS one Table HIV V90F 0 4 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. A371V 2012 PloS one Table HIV A371V 0 5 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. D123E 2012 PloS one Table HIV D123E 0 5 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. I375V 2012 PloS one Table HIV I375V 0 5 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. K366R 2012 PloS one Table HIV K366R 0 5 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. T369A 2012 PloS one Table HIV T369A 0 5 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. T369V 2012 PloS one Table HIV T369V 0 5 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. V292I 2012 PloS one Table HIV V292I 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? A98G 2012 PloS one Table HIV A98G 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? D60E 2012 PloS one Table HIV D60E 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? D67N 2012 PloS one Table HIV D67N 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? E35D 2012 PloS one Table HIV E35D 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? G190A 2012 PloS one Table HIV G190A 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? H69K 2012 PloS one Table HIV H69K 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? H69Q 2012 PloS one Table HIV H69Q 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? H69R 2012 PloS one Table HIV H69R 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? H69Y 2012 PloS one Table HIV H69Y 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? I62V 2012 PloS one Table HIV I62V 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? I64M 2012 PloS one Table HIV I64M 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? I64V 2012 PloS one Table HIV I64V 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? I93L 2012 PloS one Table HIV I93L 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? K101A 2012 PloS one Table HIV K101A 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? K101E 2012 PloS one Table HIV K101E 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? K103N 2012 PloS one Table HIV K103N 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? K103N/S 2012 PloS one Table HIV K103N;K103S 0;0 7;7 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? K103S 2012 PloS one Table HIV K103S 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? K70R 2012 PloS one Table HIV K70R 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? L210S 2012 PloS one Table HIV L210S 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? L210W 2012 PloS one Table HIV L210W 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? L63P 2012 PloS one Table HIV L63P 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? L63Q 2012 PloS one Table HIV L63Q 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? L63T 2012 PloS one Table HIV L63T 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? L89V 2012 PloS one Table HIV L89V 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? L90T 2012 PloS one Table HIV L90T 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? M184V 2012 PloS one Table HIV M184V 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? M36I 2012 PloS one Table HIV M36I 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? M41L 2012 PloS one Table HIV M41L 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Q151M 2012 PloS one Table HIV Q151M 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? T215F 2012 PloS one Table HIV T215F 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? T215Y 2012 PloS one Table HIV T215Y 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? T215Y/F 2012 PloS one Table HIV T215F;T215Y 0;0 7;7 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? V108I 2012 PloS one Table HIV V108I 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? V179I 2012 PloS one Table HIV V179I 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? V75I 2012 PloS one Table HIV V75I 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? V82I 2012 PloS one Table HIV V82I 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? V82Y 2012 PloS one Table HIV V82Y 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? V90I 2012 PloS one Table HIV V90I 0 4 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Y181C 2012 PloS one Table HIV Y181C 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Y181C/V 2012 PloS one Table HIV Y181C;Y181V 0;0 7;7 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Y181V 2012 PloS one Table HIV Y181V 0 5 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? Y188L 2012 PloS one Table HIV Y188L 0 5 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. E138D 2012 BMC infectious diseases Table HIV E138D 0 5 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. E157Q 2012 BMC infectious diseases Table HIV E157Q 0 5 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. L68V 2012 BMC infectious diseases Table HIV L68V 0 4 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. R263K 2012 BMC infectious diseases Table HIV R263K 0 5 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. T97A 2012 BMC infectious diseases Table HIV T97A 0 4 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. V151I 2012 BMC infectious diseases Table HIV V151I 0 5 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. G190A 2012 BMC infectious diseases Table HIV G190A 0 5 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. I85V 2012 BMC infectious diseases Table HIV I85V 0 4 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. K101E 2012 BMC infectious diseases Table HIV K101E 0 5 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. K103N 2012 BMC infectious diseases Table HIV K103N 0 5 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. L90M 2012 BMC infectious diseases Table HIV L90M 0 4 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. M184I 2012 BMC infectious diseases Table HIV M184I 0 5 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. M46I 2012 BMC infectious diseases Table HIV M46I 0 4 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. Y181C 2012 BMC infectious diseases Table HIV Y181C 0 5 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. D30N 2013 BMC infectious diseases Table HIV D30N 0 4 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. L90M 2013 BMC infectious diseases Table HIV L90M 0 4 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. M184V 2013 BMC infectious diseases Table HIV M184V 0 5 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. N88D 2013 BMC infectious diseases Table HIV N88D 0 4 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. T215F 2013 BMC infectious diseases Table HIV T215F 0 5 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. T215Y 2013 BMC infectious diseases Table HIV T215Y 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. A62V 2012 Journal of the International AIDS Society Table HIV A62V 0 4 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. G190A 2012 Journal of the International AIDS Society Table HIV G190A 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. K101E 2012 Journal of the International AIDS Society Table HIV K101E 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. K103N 2012 Journal of the International AIDS Society Table HIV K103N 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. K65R 2012 Journal of the International AIDS Society Table HIV K65R 0 4 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. L100I 2012 Journal of the International AIDS Society Table HIV L100I 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. M184V 2012 Journal of the International AIDS Society Table HIV M184V 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Q151M 2012 Journal of the International AIDS Society Table HIV Q151M 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. T215F 2012 Journal of the International AIDS Society Table HIV T215F 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. V108I 2012 Journal of the International AIDS Society Table HIV V108I 0 5 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Y181C 2012 Journal of the International AIDS Society Table HIV Y181C 0 5 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. L76V 2013 PloS one Table HIV L76V 0 4 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. G330E 2013 Virus research Table HIV G330E 0 5 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. R332G 2013 Virus research Table HIV R332G 0 5 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. H51Y 2013 Retrovirology Table HIV H51Y 0 4 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. R263K 2013 Retrovirology Table HIV R263K 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. E298K 2013 PLoS computational biology Table HIV E298K 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. E79D 2013 PLoS computational biology Table HIV E79D 0 4 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. I202M 2013 PLoS computational biology Table HIV I202M 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. I63V 2013 PLoS computational biology Table HIV I63V 0 4 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. K101S 2013 PLoS computational biology Table HIV K101S 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. K102Y 2013 PLoS computational biology Table HIV K102Y 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. M164L 2013 PLoS computational biology Table HIV M164L 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. N88G 2013 PLoS computational biology Table HIV N88G 0 4 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Q18N 2013 PLoS computational biology Table HIV Q18N 0 4 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. R206M 2013 PLoS computational biology Table HIV R206M 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. R307M 2013 PLoS computational biology Table HIV R307M 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. S156A 2013 PLoS computational biology Table HIV S156A 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. T216M 2013 PLoS computational biology Table HIV T216M 0 5 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. V32T 2013 PLoS computational biology Table HIV V32T 0 4 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. Y232H 2013 PLoS computational biology Table HIV Y232H 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. A98G 2013 Journal of the International AIDS Society Table HIV A98G 0 4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. D67G 2013 Journal of the International AIDS Society Table HIV D67G 0 4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. D67N 2013 Journal of the International AIDS Society Table HIV D67N 0 4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. E138K 2013 Journal of the International AIDS Society Table HIV E138K 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. F227L 2013 Journal of the International AIDS Society Table HIV F227L 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. G190A 2013 Journal of the International AIDS Society Table HIV G190A 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. G190S 2013 Journal of the International AIDS Society Table HIV G190S 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. K101E 2013 Journal of the International AIDS Society Table HIV K101E 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. K103N 2013 Journal of the International AIDS Society Table HIV K103N 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. K219E 2013 Journal of the International AIDS Society Table HIV K219E 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. K219Q 2013 Journal of the International AIDS Society Table HIV K219Q 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. K70R 2013 Journal of the International AIDS Society Table HIV K70R 0 4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. L100I 2013 Journal of the International AIDS Society Table HIV L100I 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. L210W 2013 Journal of the International AIDS Society Table HIV L210W 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. L74V 2013 Journal of the International AIDS Society Table HIV L74V 0 4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. M184I 2013 Journal of the International AIDS Society Table HIV M184I 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. M184V 2013 Journal of the International AIDS Society Table HIV M184V 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. M230I 2013 Journal of the International AIDS Society Table HIV M230I 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. M230L 2013 Journal of the International AIDS Society Table HIV M230L 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. M41L 2013 Journal of the International AIDS Society Table HIV M41L 0 4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. T215F 2013 Journal of the International AIDS Society Table HIV T215F 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. T215Y 2013 Journal of the International AIDS Society Table HIV T215Y 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. V106A 2013 Journal of the International AIDS Society Table HIV V106A 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. V106M 2013 Journal of the International AIDS Society Table HIV V106M 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. V108I 2013 Journal of the International AIDS Society Table HIV V108I 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. V75I 2013 Journal of the International AIDS Society Table HIV V75I 0 4 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. Y181C 2013 Journal of the International AIDS Society Table HIV Y181C 0 5 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. Y188L 2013 Journal of the International AIDS Society Table HIV Y188L 0 5 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. D443N 2013 Nucleic acids research Table HIV D443N 0 5 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. E478Q 2013 Nucleic acids research Table HIV E478Q 0 5 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. V75I 2013 Nucleic acids research Table HIV V75I 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. A158S 2013 PloS one Table HIV A158S 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. A62V 2013 PloS one Table HIV A62V 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. A71V 2013 PloS one Table HIV A71V 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. A98G 2013 PloS one Table HIV A98G 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. A98S 2013 PloS one Table HIV A98S 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. D177E 2013 PloS one Table HIV D177E 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. D30N 2013 PloS one Table HIV D30N 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. D67N 2013 PloS one Table HIV D67N 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. E138A 2013 PloS one Table HIV E138A 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. E35D 2013 PloS one Table HIV E35D 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. F116Y 2013 PloS one Table HIV F116Y 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. F53L 2013 PloS one Table HIV F53L 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. G179I 2013 PloS one Table HIV G179I 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. G190A/S 2013 PloS one Table HIV G190A;G190S 0;0 7;7 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. G190S 2013 PloS one Table HIV G190S 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. G48V 2013 PloS one Table HIV G48V 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. G73S 2013 PloS one Table HIV G73S 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. H69K 2013 PloS one Table HIV H69K 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. I47A 2013 PloS one Table HIV I47A 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. I50L/V 2013 PloS one Table HIV I50L;I50V 0;0 6;6 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. I54V 2013 PloS one Table HIV I54V 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. I62V 2013 PloS one Table HIV I62V 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. I84V 2013 PloS one Table HIV I84V 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. I93L 2013 PloS one Table HIV I93L 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K101E 2013 PloS one Table HIV K101E 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K101E/P 2013 PloS one Table HIV K101E;K101P 0;0 7;7 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K101N 2013 PloS one Table HIV K101N 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K103N 2013 PloS one Table HIV K103N 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K103N/S 2013 PloS one Table HIV K103N;K103S 0;0 7;7 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K103R 2013 PloS one Table HIV K103R 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K122E 2013 PloS one Table HIV K122E 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K20R 2013 PloS one Table HIV K20R 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K219E 2013 PloS one Table HIV K219E 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K219Q/E 2013 PloS one Table HIV K219E;K219Q 0;0 7;7 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K238R 2013 PloS one Table HIV K238R 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K238T 2013 PloS one Table HIV K238T 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K65R 2013 PloS one Table HIV K65R 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. K70R 2013 PloS one Table HIV K70R 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L100I 2013 PloS one Table HIV L100I 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L10V 2013 PloS one Table HIV L10V 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L210W 2013 PloS one Table HIV L210W 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L228H 2013 PloS one Table HIV L228H 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L23I 2013 PloS one Table HIV L23I 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L24I 2013 PloS one Table HIV L24I 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L33F 2013 PloS one Table HIV L33F 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L63P 2013 PloS one Table HIV L63P 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L74V/I 2013 PloS one Table HIV L74I;L74V 0;0 6;6 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L77F 2013 PloS one Table HIV L77F 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. L90M 2013 PloS one Table HIV L90M 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. M184V 2013 PloS one Table HIV M184V 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. M36I 2013 PloS one Table HIV M36I 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. M41L 2013 PloS one Table HIV M41L 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. M46I/L 2013 PloS one Table HIV M46I;M46L 0;0 6;6 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. N88D 2013 PloS one Table HIV N88D 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. N88S 2013 PloS one Table HIV N88S 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. P225H 2013 PloS one Table HIV P225H 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Q151M 2013 PloS one Table HIV Q151M 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Q174K 2013 PloS one Table HIV Q174K 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Q207A 2013 PloS one Table HIV Q207A 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. R211S 2013 PloS one Table HIV R211S 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. T215I 2013 PloS one Table HIV T215I 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. T216Y/F 2013 PloS one Table HIV T216F;T216Y 0;0 7;7 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. T69N 2013 PloS one Table HIV T69N 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. T74S 2013 PloS one Table HIV T74S 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V106A/M 2013 PloS one Table HIV V106A;V106M 0;0 7;7 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V106I 2013 PloS one Table HIV V106I 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V108I 2013 PloS one Table HIV V108I 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V118I 2013 PloS one Table HIV V118I 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V179I 2013 PloS one Table HIV V179I 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V32I 2013 PloS one Table HIV V32I 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V77I 2013 PloS one Table HIV V77I 0 4 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. V82A/S 2013 PloS one Table HIV V82A;V82S 0;0 6;6 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Y181C 2013 PloS one Table HIV Y181C 0 5 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Y188C/H 2013 PloS one Table HIV Y188C;Y188H 0;0 7;7 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. N610Q 2013 PloS one Table HIV N610Q 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). G190A 2013 PloS one Table HIV G190A 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). I85V 2013 PloS one Table HIV I85V 0 4 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). K101E 2013 PloS one Table HIV K101E 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). K103N 2013 PloS one Table HIV K103N 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). K219E 2013 PloS one Table HIV K219E 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). K219R 2013 PloS one Table HIV K219R 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). K65R 2013 PloS one Table HIV K65R 0 4 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). L74I 2013 PloS one Table HIV L74I 0 4 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). M184V 2013 PloS one Table HIV M184V 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). M46L 2013 PloS one Table HIV M46L 0 4 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). V106M 2013 PloS one Table HIV V106M 0 5 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). Y181C 2013 PloS one Table HIV Y181C 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. A68T 2013 Frontiers in microbiology Table HIV A68T 0 4 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. A833T 2013 Frontiers in microbiology Table HIV A833T 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. D374N 2013 Frontiers in microbiology Table HIV D374N 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. D571M/E 2013 Frontiers in microbiology Table HIV D571E;D571M 0;0 7;7 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. E176K 2013 Frontiers in microbiology Table HIV E176K 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. F277V 2013 Frontiers in microbiology Table HIV F277V 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. F528S/L 2013 Frontiers in microbiology Table HIV F528L;F528S 0;0 7;7 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. G62S 2013 Frontiers in microbiology Table HIV G62S 0 4 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. K141E/R 2013 Frontiers in microbiology Table HIV K141E;K141R 0;0 7;7 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. K403R 2013 Frontiers in microbiology Table HIV K403R 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. M67V/L 2013 Frontiers in microbiology Table HIV M67L;M67V 0;0 6;6 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. N295S 2013 Frontiers in microbiology Table HIV N295S 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. P26C 2013 Frontiers in microbiology Table HIV P26C 0 4 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Q341H 2013 Frontiers in microbiology Table HIV Q341H 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Q733stop 2013 Frontiers in microbiology Table HIV Q733X 0 8 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. R839K 2013 Frontiers in microbiology Table HIV R839K 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. R861K 2013 Frontiers in microbiology Table HIV R861K 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. T136M 2013 Frontiers in microbiology Table HIV T136M 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. T137I 2013 Frontiers in microbiology Table HIV T137I 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. V17L 2013 Frontiers in microbiology Table HIV V17L 0 4 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. W441R 2013 Frontiers in microbiology Table HIV W441R 0 5 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. W762stop 2013 Frontiers in microbiology Table HIV W762X 0 8 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. W782stop 2013 Frontiers in microbiology Table HIV W782X 0 8 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. F53L 2013 PloS one Table HIV F53L 0 4 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. G190A 2013 PloS one Table HIV G190A 0 5 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. I84V 2013 PloS one Table HIV I84V 0 4 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. K103N 2013 PloS one Table HIV K103N 0 5 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. L74V 2013 PloS one Table HIV L74V 0 4 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. L90M 2013 PloS one Table HIV L90M 0 4 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. M184V 2013 PloS one Table HIV M184V 0 5 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. M46I 2013 PloS one Table HIV M46I 0 4 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. M46L 2013 PloS one Table HIV M46L 0 4 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. V106I 2013 PloS one Table HIV V106I 0 5 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. V90I 2013 PloS one Table HIV V90I 0 4 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. Y115F 2013 PloS one Table HIV Y115F 0 5 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. Y188L 2013 PloS one Table HIV Y188L 0 5 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. G190A 2013 Journal of the International AIDS Society Table HIV G190A 0 5 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. K101E 2013 Journal of the International AIDS Society Table HIV K101E 0 5 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. K103N 2013 Journal of the International AIDS Society Table HIV K103N 0 5 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. K65R 2013 Journal of the International AIDS Society Table HIV K65R 0 4 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. M184V/I 2013 Journal of the International AIDS Society Table HIV M184I;M184V 0;0 7;7 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Q151M 2013 Journal of the International AIDS Society Table HIV Q151M 0 5 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Y181C 2013 Journal of the International AIDS Society Table HIV Y181C 0 5 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. I408T 2013 AIDS research and therapy Table HIV I408T 0 5 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. L317W 2013 AIDS research and therapy Table HIV L317W 0 5 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. V169M 2013 AIDS research and therapy Table HIV V169M 0 5 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. D116A 2013 Retrovirology Table HIV D116A 0 5 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. D202G 2013 Retrovirology Table HIV D202G 0 5 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. H12Y 2013 Retrovirology Table HIV H12Y 0 4 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. K111E 2013 Retrovirology Table HIV K111E 0 5 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. K71R 2013 Retrovirology Table HIV K71R 0 4 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Q137R 2013 Retrovirology Table HIV Q137R 0 5 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. S147G 2013 Retrovirology Table HIV S147G 0 5 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. K65R 2013 Retrovirology Table HIV K65R 0 4 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. D443N 2013 Retrovirology Table HIV D443N 0 5 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. A71V 2013 PloS one Table HIV A71V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. D30N 2013 PloS one Table HIV D30N 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. F53L 2013 PloS one Table HIV F53L 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. G48V 2013 PloS one Table HIV G48V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. G73S 2013 PloS one Table HIV G73S 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. I47A 2013 PloS one Table HIV I47A 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. I47V 2013 PloS one Table HIV I47V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. I50L 2013 PloS one Table HIV I50L 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. I50V 2013 PloS one Table HIV I50V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. I54L/M 2013 PloS one Table HIV I54L;I54M 0;0 6;6 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. I54V 2013 PloS one Table HIV I54V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. I84V 2013 PloS one Table HIV I84V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L10F 2013 PloS one Table HIV L10F 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L10I 2013 PloS one Table HIV L10I 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L24I 2013 PloS one Table HIV L24I 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L33F 2013 PloS one Table HIV L33F 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L76V 2013 PloS one Table HIV L76V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L89V 2013 PloS one Table HIV L89V 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. L90M 2013 PloS one Table HIV L90M 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. M184V/I 2013 PloS one Table HIV M184I;M184V 0;0 7;7 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. M46I 2013 PloS one Table HIV M46I 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. M46I/L 2013 PloS one Table HIV M46I;M46L 0;0 6;6 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. M46L 2013 PloS one Table HIV M46L 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. N83D 2013 PloS one Table HIV N83D 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. N88S 2013 PloS one Table HIV N88S 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. T74P 2013 PloS one Table HIV T74P 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. V11I 2013 PloS one Table HIV V11I 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. V32I 2013 PloS one Table HIV V32I 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. V82A 2013 PloS one Table HIV V82A 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. V82C 2013 PloS one Table HIV V82C 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. V82M 2013 PloS one Table HIV V82M 0 4 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. V82T/S 2013 PloS one Table HIV V82S;V82T 0;0 6;6 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. N276D 2013 PloS one Table HIV N276D 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. D30N 2013 The Journal of infectious diseases Table HIV D30N 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. D67E 2013 The Journal of infectious diseases Table HIV D67E 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. D67G 2013 The Journal of infectious diseases Table HIV D67G 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. D67N 2013 The Journal of infectious diseases Table HIV D67N 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. F53L 2013 The Journal of infectious diseases Table HIV F53L 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. G190A 2013 The Journal of infectious diseases Table HIV G190A 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. G190E 2013 The Journal of infectious diseases Table HIV G190E 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. G48 V 2013 The Journal of infectious diseases Table HIV G48V 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. G73 T 2013 The Journal of infectious diseases Table HIV G73T 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. G73S 2013 The Journal of infectious diseases Table HIV G73S 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I47 V 2013 The Journal of infectious diseases Table HIV I47V 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I47A 2013 The Journal of infectious diseases Table HIV I47A 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I50 V 2013 The Journal of infectious diseases Table HIV I50V 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I54 T 2013 The Journal of infectious diseases Table HIV I54T 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I54A 2013 The Journal of infectious diseases Table HIV I54A 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I54L 2013 The Journal of infectious diseases Table HIV I54L 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I54V 2013 The Journal of infectious diseases Table HIV I54V 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I84V 2013 The Journal of infectious diseases Table HIV I84V 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. I85 V 2013 The Journal of infectious diseases Table HIV I85V 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K101E 2013 The Journal of infectious diseases Table HIV K101E 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K101P 2013 The Journal of infectious diseases Table HIV K101P 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K103N 2013 The Journal of infectious diseases Table HIV K103N 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K103S 2013 The Journal of infectious diseases Table HIV K103S 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K219E 2013 The Journal of infectious diseases Table HIV K219E 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K219N 2013 The Journal of infectious diseases Table HIV K219N 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K219Q 2013 The Journal of infectious diseases Table HIV K219Q 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K219R 2013 The Journal of infectious diseases Table HIV K219R 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K65R 2013 The Journal of infectious diseases Table HIV K65R 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K70E 2013 The Journal of infectious diseases Table HIV K70E 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. K70R 2013 The Journal of infectious diseases Table HIV K70R 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. L100I 2013 The Journal of infectious diseases Table HIV L100I 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. L210W 2013 The Journal of infectious diseases Table HIV L210W 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. L24I 2013 The Journal of infectious diseases Table HIV L24I 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. L74 V 2013 The Journal of infectious diseases Table HIV L74V 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. L74I 2013 The Journal of infectious diseases Table HIV L74I 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. L90M 2013 The Journal of infectious diseases Table HIV L90M 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M184I 2013 The Journal of infectious diseases Table HIV M184I 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M184V 2013 The Journal of infectious diseases Table HIV M184V 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M230L 2013 The Journal of infectious diseases Table HIV M230L 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M41L 2013 The Journal of infectious diseases Table HIV M41L 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M46I 2013 The Journal of infectious diseases Table HIV M46I 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M46L 2013 The Journal of infectious diseases Table HIV M46L 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. N83D 2013 The Journal of infectious diseases Table HIV N83D 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. N88D 2013 The Journal of infectious diseases Table HIV N88D 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. N88S 2013 The Journal of infectious diseases Table HIV N88S 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. P225H 2013 The Journal of infectious diseases Table HIV P225H 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Q151M 2013 The Journal of infectious diseases Table HIV Q151M 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. T215F 2013 The Journal of infectious diseases Table HIV T215F 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. T215Y 2013 The Journal of infectious diseases Table HIV T215Y 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. T69D 2013 The Journal of infectious diseases Table HIV T69D 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V106A 2013 The Journal of infectious diseases Table HIV V106A 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V106M 2013 The Journal of infectious diseases Table HIV V106M 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V32I 2013 The Journal of infectious diseases Table HIV V32I 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V75 T 2013 The Journal of infectious diseases Table HIV V75T 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V75A 2013 The Journal of infectious diseases Table HIV V75A 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V75M 2013 The Journal of infectious diseases Table HIV V75M 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V82 T 2013 The Journal of infectious diseases Table HIV V82T 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V82A 2013 The Journal of infectious diseases Table HIV V82A 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V82F 2013 The Journal of infectious diseases Table HIV V82F 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V82L 2013 The Journal of infectious diseases Table HIV V82L 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. V82S 2013 The Journal of infectious diseases Table HIV V82S 0 4 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Y115F 2013 The Journal of infectious diseases Table HIV Y115F 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Y181 V 2013 The Journal of infectious diseases Table HIV Y181V 0 6 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Y181C 2013 The Journal of infectious diseases Table HIV Y181C 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Y188L 2013 The Journal of infectious diseases Table HIV Y188L 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. A62V 2013 PloS one Table HIV A62V 0 4 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. A98G 2013 PloS one Table HIV A98G 0 4 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. D67N 2013 PloS one Table HIV D67N 0 4 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. E138A 2013 PloS one Table HIV E138A 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. G190A 2013 PloS one Table HIV G190A 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. G190S 2013 PloS one Table HIV G190S 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. K101E 2013 PloS one Table HIV K101E 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. K103N 2013 PloS one Table HIV K103N 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. K219E 2013 PloS one Table HIV K219E 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. K219Q 2013 PloS one Table HIV K219Q 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. K70R 2013 PloS one Table HIV K70R 0 4 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. L210W 2013 PloS one Table HIV L210W 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. L90M 2013 PloS one Table HIV L90M 0 4 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. M184V 2013 PloS one Table HIV M184V 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. M230L 2013 PloS one Table HIV M230L 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. M41L 2013 PloS one Table HIV M41L 0 4 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. P225H 2013 PloS one Table HIV P225H 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. T215F 2013 PloS one Table HIV T215F 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. T215Y 2013 PloS one Table HIV T215Y 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. V106A 2013 PloS one Table HIV V106A 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. V106I 2013 PloS one Table HIV V106I 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. V108I 2013 PloS one Table HIV V108I 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. V90I 2013 PloS one Table HIV V90I 0 4 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. Y181C 2013 PloS one Table HIV Y181C 0 5 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. Y188L 2013 PloS one Table HIV Y188L 0 5 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. G190A 2013 PloS one Table HIV G190A 0 5 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. G73A 2013 PloS one Table HIV G73A 0 4 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. K103N 2013 PloS one Table HIV K103N 0 5 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. M184I 2013 PloS one Table HIV M184I 0 5 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. M184V 2013 PloS one Table HIV M184V 0 5 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. M46I 2013 PloS one Table HIV M46I 0 4 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. T215F 2013 PloS one Table HIV T215F 0 5 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. Y181C 2013 PloS one Table HIV Y181C 0 5 23991142 Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance. Y188H 2013 PloS one Table HIV Y188H 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. A98G 2013 PloS one Table HIV A98G 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. D30N 2013 PloS one Table HIV D30N 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. D67N 2013 PloS one Table HIV D67N 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. F116Y 2013 PloS one Table HIV F116Y 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. F227L 2013 PloS one Table HIV F227L 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. G190A 2013 PloS one Table HIV G190A 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. G190S 2013 PloS one Table HIV G190S 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. I84V 2013 PloS one Table HIV I84V 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K101E 2013 PloS one Table HIV K101E 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K101Q 2013 PloS one Table HIV K101Q 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K103N 2013 PloS one Table HIV K103N 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K103R 2013 PloS one Table HIV K103R 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K219Q/E 2013 PloS one Table HIV K219E;K219Q 0;0 7;7 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K238T 2013 PloS one Table HIV K238T 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K65R 2013 PloS one Table HIV K65R 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. K70R 2013 PloS one Table HIV K70R 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. L10F 2013 PloS one Table HIV L10F 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. L210W 2013 PloS one Table HIV L210W 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. L23I 2013 PloS one Table HIV L23I 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. L33F 2013 PloS one Table HIV L33F 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. L74I 2013 PloS one Table HIV L74I 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. L76V 2013 PloS one Table HIV L76V 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. L90M 2013 PloS one Table HIV L90M 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. M230L 2013 PloS one Table HIV M230L 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. M41L 2013 PloS one Table HIV M41L 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. N88D 2013 PloS one Table HIV N88D 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. P225H 2013 PloS one Table HIV P225H 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Q151M 2013 PloS one Table HIV Q151M 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Q58E 2013 PloS one Table HIV Q58E 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. T215F 2013 PloS one Table HIV T215F 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. T215Y 2013 PloS one Table HIV T215Y 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. T69D 2013 PloS one Table HIV T69D 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. T69ins 2013 PloS one Table HIV T69ins 0 6 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. V106A 2013 PloS one Table HIV V106A 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. V106M 2013 PloS one Table HIV V106M 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. V108I 2013 PloS one Table HIV V108I 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. V11I 2013 PloS one Table HIV V11I 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. V82A 2013 PloS one Table HIV V82A 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. V82F 2013 PloS one Table HIV V82F 0 4 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Y181C 2013 PloS one Table HIV Y181C 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Y181V 2013 PloS one Table HIV Y181V 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Y188C 2013 PloS one Table HIV Y188C 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Y188F 2013 PloS one Table HIV Y188F 0 5 24009694 Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China. Y188L 2013 PloS one Table HIV Y188L 0 5 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. A71V 2013 PloS one Table HIV A71V 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. E203D 2013 PloS one Table HIV E203D 0 5 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. G16E 2013 PloS one Table HIV G16E 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. I54V 2013 PloS one Table HIV I54V 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. I84V 2013 PloS one Table HIV I84V 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. I93L 2013 PloS one Table HIV I93L 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. K103R 2013 PloS one Table HIV K103R 0 5 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. K14R 2013 PloS one Table HIV K14R 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. L10I 2013 PloS one Table HIV L10I 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. L63A 2013 PloS one Table HIV L63A 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. L63S 2013 PloS one Table HIV L63S 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. L90M 2013 PloS one Table HIV L90M 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. M46I 2013 PloS one Table HIV M46I 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. N37S 2013 PloS one Table HIV N37S 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. P39S 2013 PloS one Table HIV P39S 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Q207E 2013 PloS one Table HIV Q207E 0 5 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Q207R 2013 PloS one Table HIV Q207R 0 5 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Q92K 2013 PloS one Table HIV Q92K 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. R211G 2013 PloS one Table HIV R211G 0 5 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. S162C 2013 PloS one Table HIV S162C 0 5 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. T12A 2013 PloS one Table HIV T12A 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. V71A 2013 PloS one Table HIV V71A 0 4 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. V82A 2013 PloS one Table HIV V82A 0 4 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. K65R 2013 PloS one Table HIV K65R 0 4 24015311 Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia. Q151M 2013 PloS one Table HIV Q151M 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. A62V 2013 Journal of the International AIDS Society Table HIV A62V 0 4 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. D67N 2013 Journal of the International AIDS Society Table HIV D67N 0 4 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. G190A 2013 Journal of the International AIDS Society Table HIV G190A 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. I54V 2013 Journal of the International AIDS Society Table HIV I54V 0 4 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. K101E 2013 Journal of the International AIDS Society Table HIV K101E 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. K101P 2013 Journal of the International AIDS Society Table HIV K101P 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. K103N 2013 Journal of the International AIDS Society Table HIV K103N 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. K219Q 2013 Journal of the International AIDS Society Table HIV K219Q 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. K70R 2013 Journal of the International AIDS Society Table HIV K70R 0 4 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. L76V 2013 Journal of the International AIDS Society Table HIV L76V 0 4 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. M184V 2013 Journal of the International AIDS Society Table HIV M184V 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. M46I 2013 Journal of the International AIDS Society Table HIV M46I 0 4 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. T215D 2013 Journal of the International AIDS Society Table HIV T215D 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. T215F 2013 Journal of the International AIDS Society Table HIV T215F 0 5 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. T69D 2013 Journal of the International AIDS Society Table HIV T69D 0 4 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. V82A 2013 Journal of the International AIDS Society Table HIV V82A 0 4 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. D67N 2013 BMC infectious diseases Table HIV D67N 0 4 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. H221Y 2013 BMC infectious diseases Table HIV H221Y 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. K101H/E 2013 BMC infectious diseases Table HIV K101E;K101H 0;0 7;7 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. K103N 2013 BMC infectious diseases Table HIV K103N 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. K219E/Q 2013 BMC infectious diseases Table HIV K219E;K219Q 0;0 7;7 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. K65R 2013 BMC infectious diseases Table HIV K65R 0 4 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. K70E 2013 BMC infectious diseases Table HIV K70E 0 4 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. K70R 2013 BMC infectious diseases Table HIV K70R 0 4 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. L210W 2013 BMC infectious diseases Table HIV L210W 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. M184V 2013 BMC infectious diseases Table HIV M184V 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. M41L 2013 BMC infectious diseases Table HIV M41L 0 4 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. P225H 2013 BMC infectious diseases Table HIV P225H 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. Q151M 2013 BMC infectious diseases Table HIV Q151M 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. T215F/I 2013 BMC infectious diseases Table HIV T215F;T215I 0;0 7;7 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. T215Y 2013 BMC infectious diseases Table HIV T215Y 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. V106M 2013 BMC infectious diseases Table HIV V106M 0 5 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. Y181C/H 2013 BMC infectious diseases Table HIV Y181C;Y181H 0;0 7;7 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. Y188L 2013 BMC infectious diseases Table HIV Y188L 0 5 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. M184V/I 2013 PloS one Table HIV M184I;M184V 0;0 7;7 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. A62A 2013 PloS one Table HIV A62A 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. A71T 2013 PloS one Table HIV A71T 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. D67D/E 2013 PloS one Table HIV D67D;D67E 0;0 6;6 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. E21R 2013 PloS one Table HIV E21R 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. E35D 2013 PloS one Table HIV E35D 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. H69K 2013 PloS one Table HIV H69K 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. I62V 2013 PloS one Table HIV I62V 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. I72V 2013 PloS one Table HIV I72V 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. I93L 2013 PloS one Table HIV I93L 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. K65R 2013 PloS one Table HIV K65R 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. K70R 2013 PloS one Table HIV K70R 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. L63P 2013 PloS one Table HIV L63P 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. L89I 2013 PloS one Table HIV L89I 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. L90M 2013 PloS one Table HIV L90M 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M184V 2013 PloS one Table HIV M184V 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M36I 2013 PloS one Table HIV M36I 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M41L 2013 PloS one Table HIV M41L 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M46I 2013 PloS one Table HIV M46I 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M46I/L 2013 PloS one Table HIV M46I;M46L 0;0 6;6 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. M46L 2013 PloS one Table HIV M46L 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. N88D 2013 PloS one Table HIV N88D 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Q92K 2013 PloS one Table HIV Q92K 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. R41K 2013 PloS one Table HIV R41K 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215D 2013 PloS one Table HIV T215D 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215F 2013 PloS one Table HIV T215F 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215H 2013 PloS one Table HIV T215H 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215I 2013 PloS one Table HIV T215I 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215L 2013 PloS one Table HIV T215L 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215N 2013 PloS one Table HIV T215N 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215S 2013 PloS one Table HIV T215S 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215V 2013 PloS one Table HIV T215V 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T215Y 2013 PloS one Table HIV T215Y 0 5 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. T74A 2013 PloS one Table HIV T74A 0 4 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. V77I 2013 PloS one Table HIV V77I 0 4 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. H69K 2014 BMC infectious diseases Table HIV H69K 0 4 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. K103N 2014 BMC infectious diseases Table HIV K103N 0 5 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. L210W 2014 BMC infectious diseases Table HIV L210W 0 5 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. M36I 2014 BMC infectious diseases Table HIV M36I 0 4 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. M41L 2014 BMC infectious diseases Table HIV M41L 0 4 24422906 Virological efficacy and immunological recovery among Ethiopian HIV-1 infected adults and children. T74S 2014 BMC infectious diseases Table HIV T74S 0 4 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. M50I 2014 Retrovirology Table HIV M50I 0 4 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. R263K 2014 Retrovirology Table HIV R263K 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. D67N 2014 Journal of the International AIDS Society Table HIV D67N 0 4 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. H221Y 2014 Journal of the International AIDS Society Table HIV H221Y 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. K101E 2014 Journal of the International AIDS Society Table HIV K101E 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. K103N 2014 Journal of the International AIDS Society Table HIV K103N 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. P225S 2014 Journal of the International AIDS Society Table HIV P225S 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. V106M 2014 Journal of the International AIDS Society Table HIV V106M 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. V90I 2014 Journal of the International AIDS Society Table HIV V90I 0 4 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. Y181C 2014 Journal of the International AIDS Society Table HIV Y181C 0 5 24439027 The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa. Y188L 2014 Journal of the International AIDS Society Table HIV Y188L 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. L100I 2014 AIDS research and therapy Table HIV L100I 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. L210W 2014 AIDS research and therapy Table HIV L210W 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. M230L 2014 AIDS research and therapy Table HIV M230L 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. M41L 2014 AIDS research and therapy Table HIV M41L 0 4 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. P225H 2014 AIDS research and therapy Table HIV P225H 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. Q151M 2014 AIDS research and therapy Table HIV Q151M 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. V106M 2014 AIDS research and therapy Table HIV V106M 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. V108I 2014 AIDS research and therapy Table HIV V108I 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. V82A 2014 AIDS research and therapy Table HIV V82A 0 4 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. Y115F 2014 AIDS research and therapy Table HIV Y115F 0 5 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. Y181C 2014 AIDS research and therapy Table HIV Y181C 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. D67N 2014 AIDS research and therapy Table HIV D67N 0 4 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. F227L 2014 AIDS research and therapy Table HIV F227L 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. G190A 2014 AIDS research and therapy Table HIV G190A 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K101E 2014 AIDS research and therapy Table HIV K101E 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K101Q 2014 AIDS research and therapy Table HIV K101Q 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K103N 2014 AIDS research and therapy Table HIV K103N 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K103S 2014 AIDS research and therapy Table HIV K103S 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K219Q 2014 AIDS research and therapy Table HIV K219Q 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K238T 2014 AIDS research and therapy Table HIV K238T 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K65R 2014 AIDS research and therapy Table HIV K65R 0 4 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. K70R 2014 AIDS research and therapy Table HIV K70R 0 4 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. L74V 2014 AIDS research and therapy Table HIV L74V 0 4 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. M184V 2014 AIDS research and therapy Table HIV M184V 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. M41L 2014 AIDS research and therapy Table HIV M41L 0 4 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. T215Y 2014 AIDS research and therapy Table HIV T215Y 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. V106A 2014 AIDS research and therapy Table HIV V106A 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. Y181C 2014 AIDS research and therapy Table HIV Y181C 0 5 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. Y188L 2014 AIDS research and therapy Table HIV Y188L 0 5 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. E138K 2014 Journal of medicinal chemistry Table HIV E138K 0 5 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. G118R 2014 Journal of medicinal chemistry Table HIV G118R 0 5 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. G140S 2014 Journal of medicinal chemistry Table HIV G140S 0 5 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. N155H 2014 Journal of medicinal chemistry Table HIV N155H 0 5 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Q148H 2014 Journal of medicinal chemistry Table HIV Q148H 0 5 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Q148K 2014 Journal of medicinal chemistry Table HIV Q148K 0 5 24471816 Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants. Y143R 2014 Journal of medicinal chemistry Table HIV Y143R 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. A417T 2014 PloS one Table HIV A417T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. A417V 2014 PloS one Table HIV A417V 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. A519G 2014 PloS one Table HIV A519G 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. A602G 2014 PloS one Table HIV A602G 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. A803T 2014 PloS one Table HIV A803T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. C541T 2014 PloS one Table HIV C541T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. C566T 2014 PloS one Table HIV C566T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. C641C/T 2014 PloS one Table HIV C641C;C641T 0;0 7;7 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. C641T 2014 PloS one Table HIV C641T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. C745T 2014 PloS one Table HIV C745T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. D511G 2014 PloS one Table HIV D511G 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. E203K 2014 PloS one Table HIV E203K 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. E79K 2014 PloS one Table HIV E79K 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G196G/R 2014 PloS one Table HIV G196G;G196R 0;0 7;7 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G196R 2014 PloS one Table HIV G196R 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G347E 2014 PloS one Table HIV G347E 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G589A 2014 PloS one Table HIV G589A 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G62D 2014 PloS one Table HIV G62D 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G635A 2014 PloS one Table HIV G635A 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G728A 2014 PloS one Table HIV G728A 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G741A 2014 PloS one Table HIV G741A 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G893A 2014 PloS one Table HIV G893A 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. H208L 2014 PloS one Table HIV H208L 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. I40V 2014 PloS one Table HIV I40V 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. I702V 2014 PloS one Table HIV I702V 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. K103N 2014 PloS one Table HIV K103N 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. K275R 2014 PloS one Table HIV K275R 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. K558R 2014 PloS one Table HIV K558R 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. K631E 2014 PloS one Table HIV K631E 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. L214F 2014 PloS one Table HIV L214F 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. L24Q 2014 PloS one Table HIV L24Q 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. L74V 2014 PloS one Table HIV L74V 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. L802F 2014 PloS one Table HIV L802F 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. L852I 2014 PloS one Table HIV L852I 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. M357R 2014 PloS one Table HIV M357R 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. M357T 2014 PloS one Table HIV M357T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. M543I 2014 PloS one Table HIV M543I 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. N405K 2014 PloS one Table HIV N405K 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. N523S 2014 PloS one Table HIV N523S 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. P225H 2014 PloS one Table HIV P225H 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. P421S 2014 PloS one Table HIV P421S 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. P421T 2014 PloS one Table HIV P421T 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. P741L 2014 PloS one Table HIV P741L 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Q164H 2014 PloS one Table HIV Q164H 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Q507H 2014 PloS one Table HIV Q507H 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Q835R 2014 PloS one Table HIV Q835R 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. R120K 2014 PloS one Table HIV R120K 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. R277K 2014 PloS one Table HIV R277K 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. R435K 2014 PloS one Table HIV R435K 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. R751G 2014 PloS one Table HIV R751G 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. S116N 2014 PloS one Table HIV S116N 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. S627K 2014 PloS one Table HIV S627K 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. T136A 2014 PloS one Table HIV T136A 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. T286A 2014 PloS one Table HIV T286A 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. T69N 2014 PloS one Table HIV T69N 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. T829C 2014 PloS one Table HIV T829C 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. V108I 2014 PloS one Table HIV V108I 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. V562L 2014 PloS one Table HIV V562L 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. V67L 2014 PloS one Table HIV V67L 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. V67M 2014 PloS one Table HIV V67M 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. V75L 2014 PloS one Table HIV V75L 0 4 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. V837G 2014 PloS one Table HIV V837G 0 5 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. W345R 2014 PloS one Table HIV W345R 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. K258E 2014 Nucleic acids research Table HIV K258E 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. N120A 2014 Nucleic acids research Table HIV N120A 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. N120E 2014 Nucleic acids research Table HIV N120E 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. N232R 2014 Nucleic acids research Table HIV N232R 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. R231E 2014 Nucleic acids research Table HIV R231E 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. R231H 2014 Nucleic acids research Table HIV R231H 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. R231Q 2014 Nucleic acids research Table HIV R231Q 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. R231S 2014 Nucleic acids research Table HIV R231S 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. S119A 2014 Nucleic acids research Table HIV S119A 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. S119T 2014 Nucleic acids research Table HIV S119T 0 5 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. S230N 2014 Nucleic acids research Table HIV S230N 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. A71T 2014 PloS one Table HIV A71T 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. A71T/V 2014 PloS one Table HIV A71T;A71V 0;0 6;6 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. A71V 2014 PloS one Table HIV A71V 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. A98G 2014 PloS one Table HIV A98G 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. D67H 2014 PloS one Table HIV D67H 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. D67N 2014 PloS one Table HIV D67N 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. G190A 2014 PloS one Table HIV G190A 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K101E 2014 PloS one Table HIV K101E 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K103N 2014 PloS one Table HIV K103N 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K219E 2014 PloS one Table HIV K219E 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K219Q/E 2014 PloS one Table HIV K219E;K219Q 0;0 7;7 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K70N 2014 PloS one Table HIV K70N 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K70Q/N 2014 PloS one Table HIV K70N;K70Q 0;0 6;6 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. K70R 2014 PloS one Table HIV K70R 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. L10I 2014 PloS one Table HIV L10I 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. L210W 2014 PloS one Table HIV L210W 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. M184L 2014 PloS one Table HIV M184L 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. M184V 2014 PloS one Table HIV M184V 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. M41L 2014 PloS one Table HIV M41L 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Q58E 2014 PloS one Table HIV Q58E 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T215F 2014 PloS one Table HIV T215F 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T215F/Y 2014 PloS one Table HIV T215F;T215Y 0;0 7;7 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T215Y 2014 PloS one Table HIV T215Y 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T69A 2014 PloS one Table HIV T69A 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T69A/N 2014 PloS one Table HIV T69A;T69N 0;0 6;6 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T69N 2014 PloS one Table HIV T69N 0 4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T69N/S 2014 PloS one Table HIV T69N;T69S 0;0 6;6 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. V108I 2014 PloS one Table HIV V108I 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. V179D 2014 PloS one Table HIV V179D 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. V179D/E 2014 PloS one Table HIV V179D;V179E 0;0 7;7 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. V179E 2014 PloS one Table HIV V179E 0 5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Y181C 2014 PloS one Table HIV Y181C 0 5 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. C67F 2014 BMC bioinformatics Table HIV C67F 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. D29V 2014 BMC bioinformatics Table HIV D29V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. D30N 2014 BMC bioinformatics Table HIV D30N 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. E35D 2014 BMC bioinformatics Table HIV E35D 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. E65D 2014 BMC bioinformatics Table HIV E65D 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. G17D 2014 BMC bioinformatics Table HIV G17D 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. G48V 2014 BMC bioinformatics Table HIV G48V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. G68E 2014 BMC bioinformatics Table HIV G68E 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. H69Q 2014 BMC bioinformatics Table HIV H69Q 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. H69Y 2014 BMC bioinformatics Table HIV H69Y 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I13V 2014 BMC bioinformatics Table HIV I13V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I15V 2014 BMC bioinformatics Table HIV I15V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I47V 2014 BMC bioinformatics Table HIV I47V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I50L 2014 BMC bioinformatics Table HIV I50L 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I50V 2014 BMC bioinformatics Table HIV I50V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I54M 2014 BMC bioinformatics Table HIV I54M 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I72R 2014 BMC bioinformatics Table HIV I72R 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I84V 2014 BMC bioinformatics Table HIV I84V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. I93F 2014 BMC bioinformatics Table HIV I93F 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. K14R 2014 BMC bioinformatics Table HIV K14R 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. K43R 2014 BMC bioinformatics Table HIV K43R 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. K70E 2014 BMC bioinformatics Table HIV K70E 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. K70I 2014 BMC bioinformatics Table HIV K70I 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. K70R/T 2014 BMC bioinformatics Table HIV K70R;K70T 0;0 6;6 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L19I 2014 BMC bioinformatics Table HIV L19I 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L63A 2014 BMC bioinformatics Table HIV L63A 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L63G 2014 BMC bioinformatics Table HIV L63G 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L63H 2014 BMC bioinformatics Table HIV L63H 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L63R 2014 BMC bioinformatics Table HIV L63R 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L63S 2014 BMC bioinformatics Table HIV L63S 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L63S/V 2014 BMC bioinformatics Table HIV L63S;L63V 0;0 6;6 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L76V 2014 BMC bioinformatics Table HIV L76V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. L90M 2014 BMC bioinformatics Table HIV L90M 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. M46I 2014 BMC bioinformatics Table HIV M46I 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. N37D 2014 BMC bioinformatics Table HIV N37D 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. N37E 2014 BMC bioinformatics Table HIV N37E 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. N37S 2014 BMC bioinformatics Table HIV N37S 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. N83D 2014 BMC bioinformatics Table HIV N83D 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. N88S 2014 BMC bioinformatics Table HIV N88S 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. P39S 2014 BMC bioinformatics Table HIV P39S 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. P79L 2014 BMC bioinformatics Table HIV P79L 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Q18H 2014 BMC bioinformatics Table HIV Q18H 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Q58E 2014 BMC bioinformatics Table HIV Q58E 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Q61E 2014 BMC bioinformatics Table HIV Q61E 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Q92G 2014 BMC bioinformatics Table HIV Q92G 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Q92G/K 2014 BMC bioinformatics Table HIV Q92G;Q92K 0;0 6;6 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Q92K 2014 BMC bioinformatics Table HIV Q92K 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. R41K 2014 BMC bioinformatics Table HIV R41K 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. R57K 2014 BMC bioinformatics Table HIV R57K 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. T12A 2014 BMC bioinformatics Table HIV T12A 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. T12I 2014 BMC bioinformatics Table HIV T12I 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. T12P/S 2014 BMC bioinformatics Table HIV T12P;T12S 0;0 6;6 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. T74P 2014 BMC bioinformatics Table HIV T74P 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. T91V 2014 BMC bioinformatics Table HIV T91V 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. V32I 2014 BMC bioinformatics Table HIV V32I 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. V82A 2014 BMC bioinformatics Table HIV V82A 0 4 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. V82L 2014 BMC bioinformatics Table HIV V82L 0 4 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. E399D 2014 The Journal of antimicrobial chemotherapy Table HIV E399D 0 5 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. K65R 2014 The Journal of antimicrobial chemotherapy Table HIV K65R 0 4 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. L74V 2014 The Journal of antimicrobial chemotherapy Table HIV L74V 0 4 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. M184V 2014 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. N348I 2014 The Journal of antimicrobial chemotherapy Table HIV N348I 0 5 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. Y115F 2014 The Journal of antimicrobial chemotherapy Table HIV Y115F 0 5 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. A92E 2014 PloS one Table HIV A92E 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. A153G 2014 PloS one Table HIV A153G 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. D232N 2014 PloS one Table HIV D232N 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. E85K 2014 PloS one Table HIV E85K 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. E92A 2014 PloS one Table HIV E92A 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. E92E/Q 2014 PloS one Table HIV E92E;E92Q 0;0 6;6 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. E92G 2014 PloS one Table HIV E92G 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. E92Q 2014 PloS one Table HIV E92Q 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. H157N/S 2014 PloS one Table HIV H157N;H157S 0;0 7;7 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. H157S 2014 PloS one Table HIV H157S 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. I84V 2014 PloS one Table HIV I84V 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. K127R 2014 PloS one Table HIV K127R 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. K236T 2014 PloS one Table HIV K236T 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. K46R 2014 PloS one Table HIV K46R 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. K71R 2014 PloS one Table HIV K71R 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. L242P 2014 PloS one Table HIV L242P 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. N155H 2014 PloS one Table HIV N155H 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. N160K 2014 PloS one Table HIV N160K 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Q148R 2014 PloS one Table HIV Q148R 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Q44H 2014 PloS one Table HIV Q44H 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Q45H 2014 PloS one Table HIV Q45H 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Q91R 2014 PloS one Table HIV Q91R 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. S163D 2014 PloS one Table HIV S163D 0 5 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. T97A 2014 PloS one Table HIV T97A 0 4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. V151I 2014 PloS one Table HIV V151I 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. A71T 2014 The Journal of antimicrobial chemotherapy Table HIV A71T 0 4 24729604 HIV-1 drug mutations in children from northern Tanzania. G190A 2014 The Journal of antimicrobial chemotherapy Table HIV G190A 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. K103N 2014 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. M184V 2014 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. T215F 2014 The Journal of antimicrobial chemotherapy Table HIV T215F 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. T215S 2014 The Journal of antimicrobial chemotherapy Table HIV T215S 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. T215Y 2014 The Journal of antimicrobial chemotherapy Table HIV T215Y 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. T69D 2014 The Journal of antimicrobial chemotherapy Table HIV T69D 0 4 24729604 HIV-1 drug mutations in children from northern Tanzania. T69K 2014 The Journal of antimicrobial chemotherapy Table HIV T69K 0 4 24729604 HIV-1 drug mutations in children from northern Tanzania. V106I 2014 The Journal of antimicrobial chemotherapy Table HIV V106I 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. V118I 2014 The Journal of antimicrobial chemotherapy Table HIV V118I 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. V179T 2014 The Journal of antimicrobial chemotherapy Table HIV V179T 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. V75I 2014 The Journal of antimicrobial chemotherapy Table HIV V75I 0 4 24729604 HIV-1 drug mutations in children from northern Tanzania. V75I/V 2014 The Journal of antimicrobial chemotherapy Table HIV V75I;V75V 0;0 6;6 24729604 HIV-1 drug mutations in children from northern Tanzania. Y181C 2014 The Journal of antimicrobial chemotherapy Table HIV Y181C 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. Y188L 2014 The Journal of antimicrobial chemotherapy Table HIV Y188L 0 5 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. I85V 2014 The Journal of infectious diseases Table HIV I85V 0 4 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. K101E 2014 The Journal of infectious diseases Table HIV K101E 0 5 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. K103N 2014 The Journal of infectious diseases Table HIV K103N 0 5 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. M184I 2014 The Journal of infectious diseases Table HIV M184I 0 5 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. M184V 2014 The Journal of infectious diseases Table HIV M184V 0 5 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. M41L 2014 The Journal of infectious diseases Table HIV M41L 0 4 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. P225H 2014 The Journal of infectious diseases Table HIV P225H 0 5 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. T215Y 2014 The Journal of infectious diseases Table HIV T215Y 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. A98G 2014 PloS one Table HIV A98G 0 4 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. G190A 2014 PloS one Table HIV G190A 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. H221Y 2014 PloS one Table HIV H221Y 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. I132L 2014 PloS one Table HIV I132L 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. K101Q 2014 PloS one Table HIV K101Q 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. K103N 2014 PloS one Table HIV K103N 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. L228R 2014 PloS one Table HIV L228R 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. M184V 2014 PloS one Table HIV M184V 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. R135L 2014 PloS one Table HIV R135L 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. T139K 2014 PloS one Table HIV T139K 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. T139R 2014 PloS one Table HIV T139R 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. V179D 2014 PloS one Table HIV V179D 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. W88C 2014 PloS one Table HIV W88C 0 4 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Y181C 2014 PloS one Table HIV Y181C 0 5 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Y188L 2014 PloS one Table HIV Y188L 0 5 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. E138G 2014 Journal of the International AIDS Society Table HIV E138G 0 5 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. G190A 2014 Journal of the International AIDS Society Table HIV G190A 0 5 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. K101E 2014 Journal of the International AIDS Society Table HIV K101E 0 5 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. V179D 2014 Journal of the International AIDS Society Table HIV V179D 0 5 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Y181C 2014 Journal of the International AIDS Society Table HIV Y181C 0 5 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. Y181C 2014 Journal of chemical theory and computation Table HIV Y181C 0 5 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. H221Y 2014 BMC infectious diseases Table HIV H221Y 0 5 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. K101Q 2014 BMC infectious diseases Table HIV K101Q 0 5 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Y181C 2014 BMC infectious diseases Table HIV Y181C 0 5 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. G306A 2014 PloS one Table HIV G306A 0 5 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. S322A 2014 PloS one Table HIV S322A 0 5 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. A98S 2014 PloS one Table HIV A98S 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. D67N 2014 PloS one Table HIV D67N 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. E138A 2014 PloS one Table HIV E138A 0 5 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. E138K 2014 PloS one Table HIV E138K 0 5 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. G190E 2014 PloS one Table HIV G190E 0 5 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. K65R 2014 PloS one Table HIV K65R 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. L101Q 2014 PloS one Table HIV L101Q 0 5 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. M41I 2014 PloS one Table HIV M41I 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. M46I 2014 PloS one Table HIV M46I 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. M46L 2014 PloS one Table HIV M46L 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. T215A 2014 PloS one Table HIV T215A 0 5 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. T69A 2014 PloS one Table HIV T69A 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. T69P 2014 PloS one Table HIV T69P 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. V106M 2014 PloS one Table HIV V106M 0 5 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. V75A 2014 PloS one Table HIV V75A 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. V90I 2014 PloS one Table HIV V90I 0 4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. Y181C 2014 PloS one Table HIV Y181C 0 5 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. G190A 2014 AIDS research and therapy Table HIV G190A 0 5 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. L210W 2014 AIDS research and therapy Table HIV L210W 0 5 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. Y181C 2014 AIDS research and therapy Table HIV Y181C 0 5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. L10R 2014 PloS one Table HIV L10R 0 4 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. L214F 2014 PloS one Table HIV L214F 0 5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. M184I 2014 PloS one Table HIV M184I 0 5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. M184V 2014 PloS one Table HIV M184V 0 5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. M46I 2014 PloS one Table HIV M46I 0 4 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. D250C 2014 Nucleic acids research Table HIV D250C 0 5 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. E138D 2014 Nucleic acids research Table HIV E138D 0 5 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. K101R 2014 Nucleic acids research Table HIV K101R 0 5 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. K103N 2014 Nucleic acids research Table HIV K103N 0 5 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. T139C 2014 Nucleic acids research Table HIV T139C 0 5 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. E138K 2014 Viruses Table HIV E138K 0 5 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. M184V 2014 Viruses Table HIV M184V 0 5 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. R263K 2014 Viruses Table HIV R263K 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. A364G 2014 Retrovirology Table HIV A364G 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. A373T 2014 Retrovirology Table HIV A373T 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. A374T 2014 Retrovirology Table HIV A374T 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. A375T 2014 Retrovirology Table HIV A375T 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. A431V 2014 Retrovirology Table HIV A431V 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. E428D/Q 2014 Retrovirology Table HIV E428D;E428Q 0;0 7;7 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. E477Q 2014 Retrovirology Table HIV E477Q 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. F363L 2014 Retrovirology Table HIV F363L 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. G381R 2014 Retrovirology Table HIV G381R 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. G381S 2014 Retrovirology Table HIV G381S 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. G420A 2014 Retrovirology Table HIV G420A 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. G443R 2014 Retrovirology Table HIV G443R 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. G446E 2014 Retrovirology Table HIV G446E 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. I376A/V 2014 Retrovirology Table HIV I376A;I376V 0;0 7;7 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. I376V 2014 Retrovirology Table HIV I376V 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. I437V 2014 Retrovirology Table HIV I437V 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. I469T 2014 Retrovirology Table HIV I469T 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. K380R 2014 Retrovirology Table HIV K380R 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. K411Q 2014 Retrovirology Table HIV K411Q 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. K415R 2014 Retrovirology Table HIV K415R 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. K436E 2014 Retrovirology Table HIV K436E 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. K436R 2014 Retrovirology Table HIV K436R 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. L363F 2014 Retrovirology Table HIV L363F 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. L363W 2014 Retrovirology Table HIV L363W 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. L449F 2014 Retrovirology Table HIV L449F 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. L449I 2014 Retrovirology Table HIV L449I 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. L449V 2014 Retrovirology Table HIV L449V 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. L486F 2014 Retrovirology Table HIV L486F 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. M138L 2014 Retrovirology Table HIV M138L 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. M378V 2014 Retrovirology Table HIV M378V 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. N375S 2014 Retrovirology Table HIV N375S 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. N382K 2014 Retrovirology Table HIV N382K 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. N389T 2014 Retrovirology Table HIV N389T 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. N451S 2014 Retrovirology Table HIV N451S 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P422Q 2014 Retrovirology Table HIV P422Q 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P445L 2014 Retrovirology Table HIV P445L 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P453I 2014 Retrovirology Table HIV P453I 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P453L 2014 Retrovirology Table HIV P453L 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P453L/T 2014 Retrovirology Table HIV P453L;P453T 0;0 7;7 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P453T 2014 Retrovirology Table HIV P453T 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P472S 2014 Retrovirology Table HIV P472S 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. P474L 2014 Retrovirology Table HIV P474L 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Q130R 2014 Retrovirology Table HIV Q130R 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Q430R 2014 Retrovirology Table HIV Q430R 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Q430R/G 2014 Retrovirology Table HIV Q430G;Q430R 0;0 7;7 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. R380K 2014 Retrovirology Table HIV R380K 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. R387K 2014 Retrovirology Table HIV R387K 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. R452G 2014 Retrovirology Table HIV R452G 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. R452K 2014 Retrovirology Table HIV R452K 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. R452S 2014 Retrovirology Table HIV R452S 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. S381G 2014 Retrovirology Table HIV S381G 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. S451G 2014 Retrovirology Table HIV S451G 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. S451T 2014 Retrovirology Table HIV S451T 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. T427P 2014 Retrovirology Table HIV T427P 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. V128A/T 2014 Retrovirology Table HIV V128A;V128T 0;0 7;7 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. V128I 2014 Retrovirology Table HIV V128I 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. V135I 2014 Retrovirology Table HIV V135I 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. V135M 2014 Retrovirology Table HIV V135M 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. V362I 2014 Retrovirology Table HIV V362I 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. V374A 2014 Retrovirology Table HIV V374A 0 5 25253273 HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes. Y132F 2014 Retrovirology Table HIV Y132F 0 5 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. G367R 2014 Virology journal Table HIV G367R 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. D67D 2014 PloS one Table HIV D67D 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. D67N 2014 PloS one Table HIV D67N 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K103K 2014 PloS one Table HIV K103K 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K103N 2014 PloS one Table HIV K103N 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K64K 2014 PloS one Table HIV K64K 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K65K 2014 PloS one Table HIV K65K 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K65R 2014 PloS one Table HIV K65R 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K66K 2014 PloS one Table HIV K66K 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K70K 2014 PloS one Table HIV K70K 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. K70R 2014 PloS one Table HIV K70R 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. M184M 2014 PloS one Table HIV M184M 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. M184V 2014 PloS one Table HIV M184V 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. M41L 2014 PloS one Table HIV M41L 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. M41M 2014 PloS one Table HIV M41M 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. S68G 2014 PloS one Table HIV S68G 0 4 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. T215F 2014 PloS one Table HIV T215F 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. T215T 2014 PloS one Table HIV T215T 0 5 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. T215Y 2014 PloS one Table HIV T215Y 0 5 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. K101E 2014 PloS one Table HIV K101E 0 5 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. K103N 2014 PloS one Table HIV K103N 0 5 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. L90M 2014 PloS one Table HIV L90M 0 4 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. M184V 2014 PloS one Table HIV M184V 0 5 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. M46L 2014 PloS one Table HIV M46L 0 4 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. N88S 2014 PloS one Table HIV N88S 0 4 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. T215S 2014 PloS one Table HIV T215S 0 5 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. V106I 2014 PloS one Table HIV V106I 0 5 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Y181C 2014 PloS one Table HIV Y181C 0 5 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Y188L 2014 PloS one Table HIV Y188L 0 5 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. N43D 2014 PloS one Table HIV N43D 0 4 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. S138A 2014 PloS one Table HIV S138A 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. A98G 2014 Journal of the International AIDS Society Table HIV A98G 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. D67N 2014 Journal of the International AIDS Society Table HIV D67N 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. E138G 2014 Journal of the International AIDS Society Table HIV E138G 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. E138K 2014 Journal of the International AIDS Society Table HIV E138K 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. G190A 2014 Journal of the International AIDS Society Table HIV G190A 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. I50V 2014 Journal of the International AIDS Society Table HIV I50V 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. I54V 2014 Journal of the International AIDS Society Table HIV I54V 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. I84V 2014 Journal of the International AIDS Society Table HIV I84V 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. K103N 2014 Journal of the International AIDS Society Table HIV K103N 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. K219E 2014 Journal of the International AIDS Society Table HIV K219E 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. K70R 2014 Journal of the International AIDS Society Table HIV K70R 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. L100I 2014 Journal of the International AIDS Society Table HIV L100I 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. L210W 2014 Journal of the International AIDS Society Table HIV L210W 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. L74I 2014 Journal of the International AIDS Society Table HIV L74I 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. L74V 2014 Journal of the International AIDS Society Table HIV L74V 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. L90M 2014 Journal of the International AIDS Society Table HIV L90M 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. M184V 2014 Journal of the International AIDS Society Table HIV M184V 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. M41L 2014 Journal of the International AIDS Society Table HIV M41L 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. M46I 2014 Journal of the International AIDS Society Table HIV M46I 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. M46L 2014 Journal of the International AIDS Society Table HIV M46L 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. N155H 2014 Journal of the International AIDS Society Table HIV N155H 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. Q148R 2014 Journal of the International AIDS Society Table HIV Q148R 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. T215Y 2014 Journal of the International AIDS Society Table HIV T215Y 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. T69G 2014 Journal of the International AIDS Society Table HIV T69G 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. V106I 2014 Journal of the International AIDS Society Table HIV V106I 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. V108I 2014 Journal of the International AIDS Society Table HIV V108I 0 5 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. V82A 2014 Journal of the International AIDS Society Table HIV V82A 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. V82C 2014 Journal of the International AIDS Society Table HIV V82C 0 4 25397500 Use of dolutegravir in two INI-experienced patients with multiclass resistance resulted in excellent virological and immunological responses. Y181C 2014 Journal of the International AIDS Society Table HIV Y181C 0 5 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. H171T 2014 Retrovirology Table HIV H171T 0 5 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. K65R 2014 BMC research notes Table HIV K65R 0 4 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. K70R 2014 BMC research notes Table HIV K70R 0 4 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. T215Y 2014 BMC research notes Table HIV T215Y 0 5 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. N611Q 2014 Retrovirology Table HIV N611Q 0 5 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. N625Q 2014 Retrovirology Table HIV N625Q 0 5 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. N637Q 2014 Retrovirology Table HIV N637Q 0 5 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. N674D 2014 Retrovirology Table HIV N674D 0 5 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. N674Q 2014 Retrovirology Table HIV N674Q 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. A272P 2014 BMC infectious diseases Table HIV A272P 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. A71L 2014 BMC infectious diseases Table HIV A71L 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. A71T/V 2014 BMC infectious diseases Table HIV A71T;A71V 0;0 6;6 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. E138G 2014 BMC infectious diseases Table HIV E138G 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. G190E 2014 BMC infectious diseases Table HIV G190E 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. I173K 2014 BMC infectious diseases Table HIV I173K 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. K174Q 2014 BMC infectious diseases Table HIV K174Q 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. L10I 2014 BMC infectious diseases Table HIV L10I 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. L10I/V 2014 BMC infectious diseases Table HIV L10I;L10V 0;0 6;6 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. L33F 2014 BMC infectious diseases Table HIV L33F 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. L33I 2014 BMC infectious diseases Table HIV L33I 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. L74I 2014 BMC infectious diseases Table HIV L74I 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. M46L 2014 BMC infectious diseases Table HIV M46L 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Q58E 2014 BMC infectious diseases Table HIV Q58E 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. R238K 2014 BMC infectious diseases Table HIV R238K 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. S207Q 2014 BMC infectious diseases Table HIV S207Q 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. S211K 2014 BMC infectious diseases Table HIV S211K 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. T11K 2014 BMC infectious diseases Table HIV T11K 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. V106I 2014 BMC infectious diseases Table HIV V106I 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. V11I 2014 BMC infectious diseases Table HIV V11I 0 4 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. V179D 2014 BMC infectious diseases Table HIV V179D 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. V179D/E 2014 BMC infectious diseases Table HIV V179D;V179E 0;0 7;7 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. V179E 2014 BMC infectious diseases Table HIV V179E 0 5 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. V75L 2014 BMC infectious diseases Table HIV V75L 0 4 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. M36I 2014 BMC genomics Table HIV M36I 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. A158S 2014 Retrovirology Table HIV A158S 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. A71T 2014 Retrovirology Table HIV A71T 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. A71V 2014 Retrovirology Table HIV A71V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. A98S 2014 Retrovirology Table HIV A98S 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. C67G 2014 Retrovirology Table HIV C67G 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. C67S 2014 Retrovirology Table HIV C67S 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D121Y 2014 Retrovirology Table HIV D121Y 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D123DE > DEKN 2014 Retrovirology Table HIV D123D;D123E;D123K;D123N;E123D;E123E;E123K;E123N 0;0;0;0;0;0;0;0 13;13;13;13;13;13;13;13 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D123DEG > DE 2014 Retrovirology Table HIV D123D;D123E;E123D;E123E;G123D;G123E 0;0;0;0;0;0 12;12;12;12;12;12 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D123E 2014 Retrovirology Table HIV D123E 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D177E 2014 Retrovirology Table HIV D177E 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D60E 2014 Retrovirology Table HIV D60E 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D67G 2014 Retrovirology Table HIV D67G 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D67N 2014 Retrovirology Table HIV D67N 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. D86E 2014 Retrovirology Table HIV D86E 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E122K 2014 Retrovirology Table HIV E122K 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E122P 2014 Retrovirology Table HIV E122P 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E138A 2014 Retrovirology Table HIV E138A 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E169D 2014 Retrovirology Table HIV E169D 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E194D 2014 Retrovirology Table HIV E194D 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E203D 2014 Retrovirology Table HIV E203D 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E35D 2014 Retrovirology Table HIV E35D 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E40Q 2014 Retrovirology Table HIV E40Q 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. E65EV > V 2014 Retrovirology Table HIV E65V;V65V 0;0 9;9 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. G190A 2014 Retrovirology Table HIV G190A 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. G196E 2014 Retrovirology Table HIV G196E 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. G51Q 2014 Retrovirology Table HIV G51Q 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. G51W 2014 Retrovirology Table HIV G51W 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. G68E 2014 Retrovirology Table HIV G68E 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. G73S 2014 Retrovirology Table HIV G73S 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. H221Y 2014 Retrovirology Table HIV H221Y 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. H235R 2014 Retrovirology Table HIV H235R 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. H69R 2014 Retrovirology Table HIV H69R 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I135IT > T 2014 Retrovirology Table HIV I135T;T135T 0;0 10;10 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I135L 2014 Retrovirology Table HIV I135L 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I135R 2014 Retrovirology Table HIV I135R 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I135T 2014 Retrovirology Table HIV I135T 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I135V 2014 Retrovirology Table HIV I135V 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I13V 2014 Retrovirology Table HIV I13V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I142V 2014 Retrovirology Table HIV I142V 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I15L 2014 Retrovirology Table HIV I15L 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I15V 2014 Retrovirology Table HIV I15V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I167F 2014 Retrovirology Table HIV I167F 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I178L 2014 Retrovirology Table HIV I178L 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I178M 2014 Retrovirology Table HIV I178M 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I195L 2014 Retrovirology Table HIV I195L 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I202V 2014 Retrovirology Table HIV I202V 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I50N 2014 Retrovirology Table HIV I50N 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I54V 2014 Retrovirology Table HIV I54V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I62IV > V 2014 Retrovirology Table HIV I62V;V62V 0;0 9;9 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I62V 2014 Retrovirology Table HIV I62V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I64L 2014 Retrovirology Table HIV I64L 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I64V 2014 Retrovirology Table HIV I64V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I72T 2014 Retrovirology Table HIV I72T 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I72V 2014 Retrovirology Table HIV I72V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. I93L 2014 Retrovirology Table HIV I93L 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K101H 2014 Retrovirology Table HIV K101H 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K103N 2014 Retrovirology Table HIV K103N 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K103Q 2014 Retrovirology Table HIV K103Q 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K14R 2014 Retrovirology Table HIV K14R 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K166R 2014 Retrovirology Table HIV K166R 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K20R 2014 Retrovirology Table HIV K20R 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K219E 2014 Retrovirology Table HIV K219E 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K219N 2014 Retrovirology Table HIV K219N 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K220X 2014 Retrovirology Table HIV K220X 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K223Q 2014 Retrovirology Table HIV K223Q 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K43N 2014 Retrovirology Table HIV K43N 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K49R 2014 Retrovirology Table HIV K49R 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. K64R 2014 Retrovirology Table HIV K64R 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L10I 2014 Retrovirology Table HIV L10I 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L19I 2014 Retrovirology Table HIV L19I 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L19T 2014 Retrovirology Table HIV L19T 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L19V 2014 Retrovirology Table HIV L19V 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L210E 2014 Retrovirology Table HIV L210E 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L210W 2014 Retrovirology Table HIV L210W 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L214F 2014 Retrovirology Table HIV L214F 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L63P 2014 Retrovirology Table HIV L63P 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L63S 2014 Retrovirology Table HIV L63S 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L63T 2014 Retrovirology Table HIV L63T 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L63X 2014 Retrovirology Table HIV L63X 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. L90M 2014 Retrovirology Table HIV L90M 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. M36I 2014 Retrovirology Table HIV M36I 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. M36T 2014 Retrovirology Table HIV M36T 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. M41L 2014 Retrovirology Table HIV M41L 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. M46L 2014 Retrovirology Table HIV M46L 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. P52A 2014 Retrovirology Table HIV P52A 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q145E 2014 Retrovirology Table HIV Q145E 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q197R 2014 Retrovirology Table HIV Q197R 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q207E 2014 Retrovirology Table HIV Q207E 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q207K 2014 Retrovirology Table HIV Q207K 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q207KQ > EQ 2014 Retrovirology Table HIV K207E;K207Q;Q207E;Q207Q 0;0;0;0 11;11;11;11 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q207R 2014 Retrovirology Table HIV Q207R 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q58E 2014 Retrovirology Table HIV Q58E 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Q61D 2014 Retrovirology Table HIV Q61D 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R211D 2014 Retrovirology Table HIV R211D 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R211DEKN > D 2014 Retrovirology Table HIV D211D;E211D;K211D;N211D;R211D 0;0;0;0;0 12;12;12;12;12 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R211G 2014 Retrovirology Table HIV R211G 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R211K 2014 Retrovirology Table HIV R211K 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R211M 2014 Retrovirology Table HIV R211M 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R41K 2014 Retrovirology Table HIV R41K 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R57K 2014 Retrovirology Table HIV R57K 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. R83K 2014 Retrovirology Table HIV R83K 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S162C 2014 Retrovirology Table HIV S162C 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S162D 2014 Retrovirology Table HIV S162D 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S162G 2014 Retrovirology Table HIV S162G 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S162T 2014 Retrovirology Table HIV S162T 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S162X 2014 Retrovirology Table HIV S162X 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S37D 2014 Retrovirology Table HIV S37D 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S37H 2014 Retrovirology Table HIV S37H 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S37N 2014 Retrovirology Table HIV S37N 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S37T 2014 Retrovirology Table HIV S37T 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S48Q 2014 Retrovirology Table HIV S48Q 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S68G 2014 Retrovirology Table HIV S68G 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S68K 2014 Retrovirology Table HIV S68K 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S68N 2014 Retrovirology Table HIV S68N 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. S68T 2014 Retrovirology Table HIV S68T 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T12A 2014 Retrovirology Table HIV T12A 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T12N 2014 Retrovirology Table HIV T12N 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T12S 2014 Retrovirology Table HIV T12S 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T139A 2014 Retrovirology Table HIV T139A 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T139I 2014 Retrovirology Table HIV T139I 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T165IT > I 2014 Retrovirology Table HIV I165I;T165I 0;0 10;10 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T200A 2014 Retrovirology Table HIV T200A 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T215A 2014 Retrovirology Table HIV T215A 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T215AT > A 2014 Retrovirology Table HIV A215A;T215A 0;0 10;10 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T215C 2014 Retrovirology Table HIV T215C 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T215D 2014 Retrovirology Table HIV T215D 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T215S 2014 Retrovirology Table HIV T215S 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T69E 2014 Retrovirology Table HIV T69E 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T69N 2014 Retrovirology Table HIV T69N 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. T69S 2014 Retrovirology Table HIV T69S 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. V106I 2014 Retrovirology Table HIV V106I 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. V118I 2014 Retrovirology Table HIV V118I 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. V179I 2014 Retrovirology Table HIV V179I 0 5 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. V60I 2014 Retrovirology Table HIV V60I 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. V77I 2014 Retrovirology Table HIV V77I 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. V82A 2014 Retrovirology Table HIV V82A 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. V90I 2014 Retrovirology Table HIV V90I 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Y181C 2014 Retrovirology Table HIV Y181C 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. A98G 2015 Global health action Table HIV A98G 0 4 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. D67E 2015 Global health action Table HIV D67E 0 4 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. D67R 2015 Global health action Table HIV D67R 0 4 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. E138A 2015 Global health action Table HIV E138A 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. G190A 2015 Global health action Table HIV G190A 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. G190R 2015 Global health action Table HIV G190R 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. K103E 2015 Global health action Table HIV K103E 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. K103N 2015 Global health action Table HIV K103N 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. L74V 2015 Global health action Table HIV L74V 0 4 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. M184I 2015 Global health action Table HIV M184I 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. M184V 2015 Global health action Table HIV M184V 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. T69S 2015 Global health action Table HIV T69S 0 4 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. V179E 2015 Global health action Table HIV V179E 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. V90I 2015 Global health action Table HIV V90I 0 4 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. Y115F 2015 Global health action Table HIV Y115F 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. Y181C 2015 Global health action Table HIV Y181C 0 5 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. K103N 2015 PloS one Table HIV K103N 0 5 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. K65R 2015 PloS one Table HIV K65R 0 4 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. K70E 2015 PloS one Table HIV K70E 0 4 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. K70R 2015 PloS one Table HIV K70R 0 4 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. M184V/I 2015 PloS one Table HIV M184I;M184V 0;0 7;7 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. P225H 2015 PloS one Table HIV P225H 0 5 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Q151M 2015 PloS one Table HIV Q151M 0 5 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. V106M 2015 PloS one Table HIV V106M 0 5 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Y181C 2015 PloS one Table HIV Y181C 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. K103N 2015 Nucleic acids research Table HIV K103N 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. N348I 2015 Nucleic acids research Table HIV N348I 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. T369I 2015 Nucleic acids research Table HIV T369I 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. T369V 2015 Nucleic acids research Table HIV T369V 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. T376S 2015 Nucleic acids research Table HIV T376S 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D121H 2015 Viruses Table HIV D121H 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D121Q 2015 Viruses Table HIV D121Q 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D121Y 2015 Viruses Table HIV D121Y 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D123E 2015 Viruses Table HIV D123E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D123S 2015 Viruses Table HIV D123S 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D123Y 2015 Viruses Table HIV D123Y 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D177E 2015 Viruses Table HIV D177E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D218R 2015 Viruses Table HIV D218R 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D237G 2015 Viruses Table HIV D237G 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D67E 2015 Viruses Table HIV D67E 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D67G 2015 Viruses Table HIV D67G 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D67N 2015 Viruses Table HIV D67N 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D76N 2015 Viruses Table HIV D76N 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D76X 2015 Viruses Table HIV D76X 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. D86H 2015 Viruses Table HIV D86H 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. E169Q 2015 Viruses Table HIV E169Q 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. E194A 2015 Viruses Table HIV E194A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. E233P 2015 Viruses Table HIV E233P 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. E34Q 2015 Viruses Table HIV E34Q 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. E35D 2015 Viruses Table HIV E35D 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. E79G 2015 Viruses Table HIV E79G 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. F171L 2015 Viruses Table HIV F171L 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. F214L 2015 Viruses Table HIV F214L 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. F214X 2015 Viruses Table HIV F214X 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. F227L 2015 Viruses Table HIV F227L 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. F77L 2015 Viruses Table HIV F77L 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. G16E 2015 Viruses Table HIV G16E 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. G190A 2015 Viruses Table HIV G190A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. G196E 2015 Viruses Table HIV G196E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. G73N 2015 Viruses Table HIV G73N 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. H221S 2015 Viruses Table HIV H221S 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. H235S 2015 Viruses Table HIV H235S 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. H69K 2015 Viruses Table HIV H69K 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. H96L 2015 Viruses Table HIV H96L 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I135K 2015 Viruses Table HIV I135K 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I135L 2015 Viruses Table HIV I135L 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I135R 2015 Viruses Table HIV I135R 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I135T 2015 Viruses Table HIV I135T 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I13V 2015 Viruses Table HIV I13V 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I142M 2015 Viruses Table HIV I142M 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I178L 2015 Viruses Table HIV I178L 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I202V 2015 Viruses Table HIV I202V 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I63M 2015 Viruses Table HIV I63M 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I84R 2015 Viruses Table HIV I84R 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I84T 2015 Viruses Table HIV I84T 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I93L 2015 Viruses Table HIV I93L 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. I94K 2015 Viruses Table HIV I94K 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K101E 2015 Viruses Table HIV K101E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K101Q 2015 Viruses Table HIV K101Q 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K102Q 2015 Viruses Table HIV K102Q 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K103N 2015 Viruses Table HIV K103N 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K122A 2015 Viruses Table HIV K122A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K122E 2015 Viruses Table HIV K122E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K173A 2015 Viruses Table HIV K173A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K219Q 2015 Viruses Table HIV K219Q 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K64Q 2015 Viruses Table HIV K64Q 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K65E 2015 Viruses Table HIV K65E 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K66E 2015 Viruses Table HIV K66E 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K70N 2015 Viruses Table HIV K70N 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. K73X 2015 Viruses Table HIV K73X 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L109P 2015 Viruses Table HIV L109P 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L109Q 2015 Viruses Table HIV L109Q 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L10I 2015 Viruses Table HIV L10I 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L10V 2015 Viruses Table HIV L10V 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L120F 2015 Viruses Table HIV L120F 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L19I 2015 Viruses Table HIV L19I 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L228F 2015 Viruses Table HIV L228F 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L228X 2015 Viruses Table HIV L228X 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L63P 2015 Viruses Table HIV L63P 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L74I 2015 Viruses Table HIV L74I 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L74Y 2015 Viruses Table HIV L74Y 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L76T 2015 Viruses Table HIV L76T 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L97R 2015 Viruses Table HIV L97R 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. M184V 2015 Viruses Table HIV M184V 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. M230D 2015 Viruses Table HIV M230D 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. M230E 2015 Viruses Table HIV M230E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. M230G 2015 Viruses Table HIV M230G 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. M230N 2015 Viruses Table HIV M230N 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. M36I 2015 Viruses Table HIV M36I 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. N37E 2015 Viruses Table HIV N37E 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. N37S 2015 Viruses Table HIV N37S 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. P133Q 2015 Viruses Table HIV P133Q 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. P226A 2015 Viruses Table HIV P226A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. P226X 2015 Viruses Table HIV P226X 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. P55S 2015 Viruses Table HIV P55S 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Q145H 2015 Viruses Table HIV Q145H 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Q151R 2015 Viruses Table HIV Q151R 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Q174R 2015 Viruses Table HIV Q174R 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Q197K 2015 Viruses Table HIV Q197K 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Q207A 2015 Viruses Table HIV Q207A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Q207E 2015 Viruses Table HIV Q207E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Q207X 2015 Viruses Table HIV Q207X 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. R206X 2015 Viruses Table HIV R206X 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. R211K 2015 Viruses Table HIV R211K 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. R41K 2015 Viruses Table HIV R41K 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. R57K 2015 Viruses Table HIV R57K 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. R72E 2015 Viruses Table HIV R72E 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. R72K 2015 Viruses Table HIV R72K 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. R87K 2015 Viruses Table HIV R87K 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. S162A 2015 Viruses Table HIV S162A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. S162C 2015 Viruses Table HIV S162C 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. S162T 2015 Viruses Table HIV S162T 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. T107E 2015 Viruses Table HIV T107E 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. T128P 2015 Viruses Table HIV T128P 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. T12S 2015 Viruses Table HIV T12S 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. T200A 2015 Viruses Table HIV T200A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. T69X 2015 Viruses Table HIV T69X 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. T80P 2015 Viruses Table HIV T80P 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V106A 2015 Viruses Table HIV V106A 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V106X 2015 Viruses Table HIV V106X 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V118L 2015 Viruses Table HIV V118L 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V179D 2015 Viruses Table HIV V179D 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V179F 2015 Viruses Table HIV V179F 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V60I 2015 Viruses Table HIV V60I 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V75P 2015 Viruses Table HIV V75P 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. V77I 2015 Viruses Table HIV V77I 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. W212R 2015 Viruses Table HIV W212R 0 5 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. W88C 2015 Viruses Table HIV W88C 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. W88R 2015 Viruses Table HIV W88R 0 4 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Y232S 2015 Viruses Table HIV Y232S 0 5 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. N88D 2015 Evolutionary applications Table HIV N88D 0 4 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. p1V82A 2015 Evolutionary applications Table HIV V82A 0 6 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. p6D30N 2015 Evolutionary applications Table HIV D30N 0 6 Gag 0 2 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. K103N 2015 Journal of medicinal chemistry Table HIV K103N 0 5 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. X29A 2015 Journal of medicinal chemistry Table HIV X29A 0 4 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Y181C 2015 Journal of medicinal chemistry Table HIV Y181C 0 5 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. D67N 2015 Nucleic acids research Table HIV D67N 0 4 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. K65K 2015 Nucleic acids research Table HIV K65K 0 4 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. K66K 2015 Nucleic acids research Table HIV K66K 0 4 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. K70R 2015 Nucleic acids research Table HIV K70R 0 4 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. E92Q 2015 Retrovirology Table HIV E92Q 0 4 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. G140S 2015 Retrovirology Table HIV G140S 0 5 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. N155H 2015 Retrovirology Table HIV N155H 0 5 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Q148H 2015 Retrovirology Table HIV Q148H 0 5 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Q148K 2015 Retrovirology Table HIV Q148K 0 5 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Q148R 2015 Retrovirology Table HIV Q148R 0 5 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. T97A 2015 Retrovirology Table HIV T97A 0 4 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Y143C 2015 Retrovirology Table HIV Y143C 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. E350K 2015 Retrovirology Table HIV E350K 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. I224T 2015 Retrovirology Table HIV I224T 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. K211I 2015 Retrovirology Table HIV K211I 0 5 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. S345T 2015 Retrovirology Table HIV S345T 0 5 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. A501C 2015 PloS one Table HIV A501C 0 5 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. I559P 2015 PloS one Table HIV I559P 0 5 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. S375W 2015 PloS one Table HIV S375W 0 5 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. T605C 2015 PloS one Table HIV T605C 0 5 25879488 Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011. K101E 2015 BMC public health Table HIV K101E 0 5 25879488 Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011. V179D 2015 BMC public health Table HIV V179D 0 5 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. K101E 2015 Virology journal Table HIV K101E 0 5 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. K103N 2015 Virology journal Table HIV K103N 0 5 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. K20R 2015 Virology journal Table HIV K20R 0 4 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. L10I 2015 Virology journal Table HIV L10I 0 4 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. L10I/V 2015 Virology journal Table HIV L10I;L10V 0;0 6;6 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. L33F 2015 Virology journal Table HIV L33F 0 4 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. M184M/V 2015 Virology journal Table HIV M184M;M184V 0;0 7;7 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. M184V 2015 Virology journal Table HIV M184V 0 5 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. T69D 2015 Virology journal Table HIV T69D 0 4 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. V106A 2015 Virology journal Table HIV V106A 0 5 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. Y181C 2015 Virology journal Table HIV Y181C 0 5 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. Y188C 2015 Virology journal Table HIV Y188C 0 5 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. E138A 2015 Virology journal Table HIV E138A 0 5 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. E157Q 2015 Virology journal Table HIV E157Q 0 5 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. K101E 2015 Virology journal Table HIV K101E 0 5 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. K103N 2015 Virology journal Table HIV K103N 0 5 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. L74I 2015 Virology journal Table HIV L74I 0 4 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. T74S 2015 Virology journal Table HIV T74S 0 4 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. D67N 2014 AIDS research and therapy Table HIV D67N 0 4 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. G190A 2014 AIDS research and therapy Table HIV G190A 0 5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. H221Y 2014 AIDS research and therapy Table HIV H221Y 0 5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. K101E 2014 AIDS research and therapy Table HIV K101E 0 5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. K103N 2014 AIDS research and therapy Table HIV K103N 0 5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. K103S 2014 AIDS research and therapy Table HIV K103S 0 5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. K219R 2014 AIDS research and therapy Table HIV K219R 0 5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. K70R 2014 AIDS research and therapy Table HIV K70R 0 4 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. M184V 2014 AIDS research and therapy Table HIV M184V 0 5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. M41L 2014 AIDS research and therapy Table HIV M41L 0 4 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. T69D 2014 AIDS research and therapy Table HIV T69D 0 4 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. T69N 2014 AIDS research and therapy Table HIV T69N 0 4 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Y181C 2014 AIDS research and therapy Table HIV Y181C 0 5 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. A272A/P 2014 AIDS research and therapy Table HIV A272A;A272P 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. D123D/E 2014 AIDS research and therapy Table HIV D123D;D123E 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. D123D/G 2014 AIDS research and therapy Table HIV D123D;D123G 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. D123N 2014 AIDS research and therapy Table HIV D123N 0 5 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. D177D/G 2014 AIDS research and therapy Table HIV D177D;D177G 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. E138T 2014 AIDS research and therapy Table HIV E138T 0 5 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. E224E/Q 2014 AIDS research and therapy Table HIV E224E;E224Q 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. G86G/E 2014 AIDS research and therapy Table HIV G86E;G86G 0;0 6;6 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. I142L/P 2014 AIDS research and therapy Table HIV I142L;I142P 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. I178M 2014 AIDS research and therapy Table HIV I178M 0 5 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. I195I/L 2014 AIDS research and therapy Table HIV I195I;I195L 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. I84I/V 2014 AIDS research and therapy Table HIV I84I;I84V 0;0 6;6 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. I93I/L 2014 AIDS research and therapy Table HIV I93I;I93L 0;0 6;6 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. K122K/E 2014 AIDS research and therapy Table HIV K122E;K122K 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. K22K/R 2014 AIDS research and therapy Table HIV K22K;K22R 0;0 6;6 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. M184V 2014 AIDS research and therapy Table HIV M184V 0 5 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. P39P/S 2014 AIDS research and therapy Table HIV P39P;P39S 0;0 6;6 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. R211R/K 2014 AIDS research and therapy Table HIV R211K;R211R 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. R41R/K 2014 AIDS research and therapy Table HIV R41K;R41R 0;0 6;6 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. R57R/K 2014 AIDS research and therapy Table HIV R57K;R57R 0;0 6;6 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. T165A/E 2014 AIDS research and therapy Table HIV T165A;T165E 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. T286T 2014 AIDS research and therapy Table HIV T286T 0 5 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. V245Q 2014 AIDS research and therapy Table HIV V245Q 0 5 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. V292V/I 2014 AIDS research and therapy Table HIV V292I;V292V 0;0 7;7 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. V32V 2014 AIDS research and therapy Table HIV V32V 0 4 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. V60I 2014 AIDS research and therapy Table HIV V60I 0 4 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. V77V/I 2014 AIDS research and therapy Table HIV V77I;V77V 0;0 6;6 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. E138K 2015 Acta naturae Table HIV E138K 0 5 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. G118R 2015 Acta naturae Table HIV G118R 0 5 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. G140S 2015 Acta naturae Table HIV G140S 0 5 25927004 Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study. Q148K 2015 Acta naturae Table HIV Q148K 0 5 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. D67N 2015 PloS one Table HIV D67N 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. F116Y 2015 PloS one Table HIV F116Y 0 5 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. G16E 2015 PloS one Table HIV G16E 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. H69K 2015 PloS one Table HIV H69K 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. I62V 2015 PloS one Table HIV I62V 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. I64L/M 2015 PloS one Table HIV I64L;I64M 0;0 6;6 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. I93L 2015 PloS one Table HIV I93L 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. K103N 2015 PloS one Table HIV K103N 0 5 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. K20R 2015 PloS one Table HIV K20R 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. K219E 2015 PloS one Table HIV K219E 0 5 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. K70R 2015 PloS one Table HIV K70R 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. L210W 2015 PloS one Table HIV L210W 0 5 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. L63P 2015 PloS one Table HIV L63P 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. L89M/V 2015 PloS one Table HIV L89M;L89V 0;0 6;6 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. M184V 2015 PloS one Table HIV M184V 0 5 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. M36I 2015 PloS one Table HIV M36I 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. M41L 2015 PloS one Table HIV M41L 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. T215Y 2015 PloS one Table HIV T215Y 0 5 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. T74S 2015 PloS one Table HIV T74S 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. V11I 2015 PloS one Table HIV V11I 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. V75M 2015 PloS one Table HIV V75M 0 4 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. V77I 2015 PloS one Table HIV V77I 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. D30N 2015 PloS one Table HIV D30N 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. D67G/N 2015 PloS one Table HIV D67G;D67N 0;0 6;6 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. D67N 2015 PloS one Table HIV D67N 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. G190A 2015 PloS one Table HIV G190A 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. G73S 2015 PloS one Table HIV G73S 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. I54V 2015 PloS one Table HIV I54V 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. I84V 2015 PloS one Table HIV I84V 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. I85V 2015 PloS one Table HIV I85V 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. K101E 2015 PloS one Table HIV K101E 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. K103N/S 2015 PloS one Table HIV K103N;K103S 0;0 7;7 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. K65R 2015 PloS one Table HIV K65R 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. K70E 2015 PloS one Table HIV K70E 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L100I 2015 PloS one Table HIV L100I 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L210W 2015 PloS one Table HIV L210W 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L23I 2015 PloS one Table HIV L23I 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L24I 2015 PloS one Table HIV L24I 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L74V 2015 PloS one Table HIV L74V 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L76V 2015 PloS one Table HIV L76V 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. L90M 2015 PloS one Table HIV L90M 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. M184V/I 2015 PloS one Table HIV M184I;M184V 0;0 7;7 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. M41L 2015 PloS one Table HIV M41L 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. M46L/I 2015 PloS one Table HIV M46I;M46L 0;0 6;6 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. N83D 2015 PloS one Table HIV N83D 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. N88D 2015 PloS one Table HIV N88D 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. P225H 2015 PloS one Table HIV P225H 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. T215C/E 2015 PloS one Table HIV T215C;T215E 0;0 7;7 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. T215Y 2015 PloS one Table HIV T215Y 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. T69D 2015 PloS one Table HIV T69D 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. V106M 2015 PloS one Table HIV V106M 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. V82A 2015 PloS one Table HIV V82A 0 4 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Y115F 2015 PloS one Table HIV Y115F 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Y181C 2015 PloS one Table HIV Y181C 0 5 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Y188L 2015 PloS one Table HIV Y188L 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. A62V 2015 PloS one Table HIV A62V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. A71V 2015 PloS one Table HIV A71V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. A98G 2015 PloS one Table HIV A98G 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. D177E/G 2015 PloS one Table HIV D177E;D177G 0;0 7;7 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. D67N 2015 PloS one Table HIV D67N 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. E35D 2015 PloS one Table HIV E35D 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. E44D 2015 PloS one Table HIV E44D 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. F227F/I 2015 PloS one Table HIV F227F;F227I 0;0 7;7 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. F53L 2015 PloS one Table HIV F53L 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. G16E 2015 PloS one Table HIV G16E 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. G190A 2015 PloS one Table HIV G190A 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. G190G/A 2015 PloS one Table HIV G190A;G190G 0;0 7;7 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. G73S 2015 PloS one Table HIV G73S 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. I13V 2015 PloS one Table HIV I13V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. I15V 2015 PloS one Table HIV I15V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. I47V 2015 PloS one Table HIV I47V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. I62V 2015 PloS one Table HIV I62V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. I64V 2015 PloS one Table HIV I64V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. I66F 2015 PloS one Table HIV I66F 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. I93L 2015 PloS one Table HIV I93L 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K101E 2015 PloS one Table HIV K101E 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K101Q 2015 PloS one Table HIV K101Q 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K103K/N 2015 PloS one Table HIV K103K;K103N 0;0 7;7 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K103N 2015 PloS one Table HIV K103N 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K20M 2015 PloS one Table HIV K20M 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K20R 2015 PloS one Table HIV K20R 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K20T 2015 PloS one Table HIV K20T 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K219E 2015 PloS one Table HIV K219E 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K219Q 2015 PloS one Table HIV K219Q 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K238T 2015 PloS one Table HIV K238T 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K43T 2015 PloS one Table HIV K43T 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K65R 2015 PloS one Table HIV K65R 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. K70R 2015 PloS one Table HIV K70R 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. L10V 2015 PloS one Table HIV L10V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. L210W 2015 PloS one Table HIV L210W 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. L33V 2015 PloS one Table HIV L33V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. L63P 2015 PloS one Table HIV L63P 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. L74V 2015 PloS one Table HIV L74V 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. L90M 2015 PloS one Table HIV L90M 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. M184V 2015 PloS one Table HIV M184V 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. M230L 2015 PloS one Table HIV M230L 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. M36I 2015 PloS one Table HIV M36I 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. M41L 2015 PloS one Table HIV M41L 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. M46I 2015 PloS one Table HIV M46I 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. P225H 2015 PloS one Table HIV P225H 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Q102K/R 2015 PloS one Table HIV Q102K;Q102R 0;0 7;7 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Q58E 2015 PloS one Table HIV Q58E 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. R41K 2015 PloS one Table HIV R41K 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. T215F 2015 PloS one Table HIV T215F 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. T215S 2015 PloS one Table HIV T215S 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. T215Y 2015 PloS one Table HIV T215Y 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. T69D 2015 PloS one Table HIV T69D 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. T69N 2015 PloS one Table HIV T69N 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. V106A 2015 PloS one Table HIV V106A 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. V106V/I 2015 PloS one Table HIV V106I;V106V 0;0 7;7 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. V108I 2015 PloS one Table HIV V108I 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. V118I 2015 PloS one Table HIV V118I 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. V32I 2015 PloS one Table HIV V32I 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. V75I 2015 PloS one Table HIV V75I 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. V77I 2015 PloS one Table HIV V77I 0 4 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Y181C 2015 PloS one Table HIV Y181C 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Y181I 2015 PloS one Table HIV Y181I 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Y181Y/D 2015 PloS one Table HIV Y181D;Y181Y 0;0 7;7 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Y188C 2015 PloS one Table HIV Y188C 0 5 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. Y188L 2015 PloS one Table HIV Y188L 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. A62A/V 2015 Viruses Table HIV A62A;A62V 0;0 6;6 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. E138T/A 2015 Viruses Table HIV E138A;E138T 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. E157E/Q 2015 Viruses Table HIV E157E;E157Q 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. E92E 2015 Viruses Table HIV E92E 0 4 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. E92E/Q 2015 Viruses Table HIV E92E;E92Q 0;0 6;6 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. E92Q 2015 Viruses Table HIV E92Q 0 4 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. G140C 2015 Viruses Table HIV G140C 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. G140S 2015 Viruses Table HIV G140S 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. G163G/R 2015 Viruses Table HIV G163G;G163R 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. H51H/Y 2015 Viruses Table HIV H51H;H51Y 0;0 6;6 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. K65K/R 2015 Viruses Table HIV K65K;K65R 0;0 6;6 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. K65R 2015 Viruses Table HIV K65R 0 4 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. L68V 2015 Viruses Table HIV L68V 0 4 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. L74L/M 2015 Viruses Table HIV L74L;L74M 0;0 6;6 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184I 2015 Viruses Table HIV M184I 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184I/V 2015 Viruses Table HIV M184I;M184V 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184M 2015 Viruses Table HIV M184M 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184M/I 2015 Viruses Table HIV M184I;M184M 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184M/V 2015 Viruses Table HIV M184M;M184V 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184V 2015 Viruses Table HIV M184V 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. M184V/I 2015 Viruses Table HIV M184I;M184V 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. N155H 2015 Viruses Table HIV N155H 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. N155H/N 2015 Viruses Table HIV N155H;N155N 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. N155N/H 2015 Viruses Table HIV N155H;N155N 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Q148H 2015 Viruses Table HIV Q148H 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Q148R 2015 Viruses Table HIV Q148R 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. R263K 2015 Viruses Table HIV R263K 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. R263R/K 2015 Viruses Table HIV R263K;R263R 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. S130R 2015 Viruses Table HIV S130R 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. S153A 2015 Viruses Table HIV S153A 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. T66T/I 2015 Viruses Table HIV T66I;T66T 0;0 6;6 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. T97A 2015 Viruses Table HIV T97A 0 4 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. V151I 2015 Viruses Table HIV V151I 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. V151I/V 2015 Viruses Table HIV V151I;V151V 0;0 7;7 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Y143H 2015 Viruses Table HIV Y143H 0 5 26198244 Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Y143R 2015 Viruses Table HIV Y143R 0 5 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. E138K 2015 PloS one Table HIV E138K 0 5 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. K101E 2015 PloS one Table HIV K101E 0 5 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. K103Q 2015 PloS one Table HIV K103Q 0 5 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. A71T 2015 AIDS research and therapy Table HIV A71T 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. D30N 2015 AIDS research and therapy Table HIV D30N 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. G48E 2015 AIDS research and therapy Table HIV G48E 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. G48R 2015 AIDS research and therapy Table HIV G48R 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. I13V 2015 AIDS research and therapy Table HIV I13V 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. K20I 2015 AIDS research and therapy Table HIV K20I 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. K20R 2015 AIDS research and therapy Table HIV K20R 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. L10I 2015 AIDS research and therapy Table HIV L10I 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. L10V 2015 AIDS research and therapy Table HIV L10V 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. L33F 2015 AIDS research and therapy Table HIV L33F 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. L63P 2015 AIDS research and therapy Table HIV L63P 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. L90M 2015 AIDS research and therapy Table HIV L90M 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. M46I 2015 AIDS research and therapy Table HIV M46I 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. T74S 2015 AIDS research and therapy Table HIV T74S 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. V11I 2015 AIDS research and therapy Table HIV V11I 0 4 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. V32L 2015 AIDS research and therapy Table HIV V32L 0 4 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. E92Q 2015 The Journal of antimicrobial chemotherapy Table HIV E92Q 0 4 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. G140A 2015 The Journal of antimicrobial chemotherapy Table HIV G140A 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. G140S 2015 The Journal of antimicrobial chemotherapy Table HIV G140S 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. G140S/A 2015 The Journal of antimicrobial chemotherapy Table HIV G140A;G140S 0;0 7;7 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. N155H 2015 The Journal of antimicrobial chemotherapy Table HIV N155H 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Q148H 2015 The Journal of antimicrobial chemotherapy Table HIV Q148H 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Q148H/R 2015 The Journal of antimicrobial chemotherapy Table HIV Q148H;Q148R 0;0 7;7 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Q148K 2015 The Journal of antimicrobial chemotherapy Table HIV Q148K 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Q148R 2015 The Journal of antimicrobial chemotherapy Table HIV Q148R 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. S147G 2015 The Journal of antimicrobial chemotherapy Table HIV S147G 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Y143C 2015 The Journal of antimicrobial chemotherapy Table HIV Y143C 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Y143H 2015 The Journal of antimicrobial chemotherapy Table HIV Y143H 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Y143R 2015 The Journal of antimicrobial chemotherapy Table HIV Y143R 0 5 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Y143R/C 2015 The Journal of antimicrobial chemotherapy Table HIV Y143C;Y143R 0;0 7;7 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. K103N 2015 PloS one Table HIV K103N 0 5 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. K70R 2015 PloS one Table HIV K70R 0 4 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. M184V 2015 PloS one Table HIV M184V 0 5 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. M41L 2015 PloS one Table HIV M41L 0 4 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. T215F 2015 PloS one Table HIV T215F 0 5 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. T215Y 2015 PloS one Table HIV T215Y 0 5 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Y181C 2015 PloS one Table HIV Y181C 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. E138A 2015 PloS one Table HIV E138A 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. E138G 2015 PloS one Table HIV E138G 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. E138K 2015 PloS one Table HIV E138K 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. E138R 2015 PloS one Table HIV E138R 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. G190A 2015 PloS one Table HIV G190A 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. G190G/A 2015 PloS one Table HIV G190A;G190G 0;0 7;7 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K101E 2015 PloS one Table HIV K101E 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K103K/N 2015 PloS one Table HIV K103K;K103N 0;0 7;7 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K103N 2015 PloS one Table HIV K103N 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K103R 2015 PloS one Table HIV K103R 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K65K/R 2015 PloS one Table HIV K65K;K65R 0;0 6;6 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K65R 2015 PloS one Table HIV K65R 0 4 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K70K/R 2015 PloS one Table HIV K70K;K70R 0;0 6;6 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. K70R 2015 PloS one Table HIV K70R 0 4 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. M184I 2015 PloS one Table HIV M184I 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. M184V 2015 PloS one Table HIV M184V 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. P225H 2015 PloS one Table HIV P225H 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. T215F 2015 PloS one Table HIV T215F 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. T215I 2015 PloS one Table HIV T215I 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. T215Y 2015 PloS one Table HIV T215Y 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. V106A 2015 PloS one Table HIV V106A 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. V106I 2015 PloS one Table HIV V106I 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. V106M 2015 PloS one Table HIV V106M 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. V106V/A 2015 PloS one Table HIV V106A;V106V 0;0 7;7 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. V108I 2015 PloS one Table HIV V108I 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. V90I 2015 PloS one Table HIV V90I 0 4 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Y181C 2015 PloS one Table HIV Y181C 0 5 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Y181Y/C 2015 PloS one Table HIV Y181C;Y181Y 0;0 7;7 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Y188C 2015 PloS one Table HIV Y188C 0 5 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. G190A 2015 PloS one Table HIV G190A 0 5 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. K101E 2015 PloS one Table HIV K101E 0 5 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. K103N 2015 PloS one Table HIV K103N 0 5 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. K65R 2015 PloS one Table HIV K65R 0 4 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. M184V 2015 PloS one Table HIV M184V 0 5 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. V106M 2015 PloS one Table HIV V106M 0 5 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. V90I 2015 PloS one Table HIV V90I 0 4 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Y188L 2015 PloS one Table HIV Y188L 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. A62V 2015 PloS one Table HIV A62V 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. A98G 2015 PloS one Table HIV A98G 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. D30N 2015 PloS one Table HIV D30N 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. D67E 2015 PloS one Table HIV D67E 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. D67G 2015 PloS one Table HIV D67G 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. D67H 2015 PloS one Table HIV D67H 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. D67N 2015 PloS one Table HIV D67N 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. D67T 2015 PloS one Table HIV D67T 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. E35G 2015 PloS one Table HIV E35G 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. F116Y 2015 PloS one Table HIV F116Y 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. F227L 2015 PloS one Table HIV F227L 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. F53L 2015 PloS one Table HIV F53L 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. F53Y 2015 PloS one Table HIV F53Y 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. F77L 2015 PloS one Table HIV F77L 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. G190A 2015 PloS one Table HIV G190A 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. G190C 2015 PloS one Table HIV G190C 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. G190E 2015 PloS one Table HIV G190E 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. G190S 2015 PloS one Table HIV G190S 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. H221Y 2015 PloS one Table HIV H221Y 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. I47A 2015 PloS one Table HIV I47A 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. I47V 2015 PloS one Table HIV I47V 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. I50L 2015 PloS one Table HIV I50L 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. I50V 2015 PloS one Table HIV I50V 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. I54L 2015 PloS one Table HIV I54L 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. I54M 2015 PloS one Table HIV I54M 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. I85V 2015 PloS one Table HIV I85V 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K101E 2015 PloS one Table HIV K101E 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K101P 2015 PloS one Table HIV K101P 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K103R 2015 PloS one Table HIV K103R 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K20I 2015 PloS one Table HIV K20I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K219R 2015 PloS one Table HIV K219R 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K238N 2015 PloS one Table HIV K238N 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K238T 2015 PloS one Table HIV K238T 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K43T 2015 PloS one Table HIV K43T 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K65N 2015 PloS one Table HIV K65N 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K65R 2015 PloS one Table HIV K65R 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K70E 2015 PloS one Table HIV K70E 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K70G 2015 PloS one Table HIV K70G 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K70N 2015 PloS one Table HIV K70N 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K70Q 2015 PloS one Table HIV K70Q 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. K70R 2015 PloS one Table HIV K70R 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L100I 2015 PloS one Table HIV L100I 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L10F 2015 PloS one Table HIV L10F 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L210W 2015 PloS one Table HIV L210W 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L23I 2015 PloS one Table HIV L23I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L24I 2015 PloS one Table HIV L24I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L33F 2015 PloS one Table HIV L33F 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L74I 2015 PloS one Table HIV L74I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L74V 2015 PloS one Table HIV L74V 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L76V 2015 PloS one Table HIV L76V 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. L90M 2015 PloS one Table HIV L90M 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. M230L 2015 PloS one Table HIV M230L 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. M41L 2015 PloS one Table HIV M41L 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. N83D 2015 PloS one Table HIV N83D 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. N88D 2015 PloS one Table HIV N88D 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. N88S 2015 PloS one Table HIV N88S 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. P225H 2015 PloS one Table HIV P225H 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Q151M 2015 PloS one Table HIV Q151M 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Q58E 2015 PloS one Table HIV Q58E 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T215A 2015 PloS one Table HIV T215A 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T215F 2015 PloS one Table HIV T215F 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T215Y 2015 PloS one Table HIV T215Y 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69A 2015 PloS one Table HIV T69A 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69C 2015 PloS one Table HIV T69C 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69D 2015 PloS one Table HIV T69D 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69G 2015 PloS one Table HIV T69G 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69I 2015 PloS one Table HIV T69I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69ins 2015 PloS one Table HIV T69ins 0 6 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69N 2015 PloS one Table HIV T69N 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T69S 2015 PloS one Table HIV T69S 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. T74S 2015 PloS one Table HIV T74S 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V106A 2015 PloS one Table HIV V106A 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V106M 2015 PloS one Table HIV V106M 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V108I 2015 PloS one Table HIV V108I 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V118I 2015 PloS one Table HIV V118I 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V179D 2015 PloS one Table HIV V179D 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V179E 2015 PloS one Table HIV V179E 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V179F 2015 PloS one Table HIV V179F 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V179L 2015 PloS one Table HIV V179L 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V32I 2015 PloS one Table HIV V32I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V75A 2015 PloS one Table HIV V75A 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V75I 2015 PloS one Table HIV V75I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V75L 2015 PloS one Table HIV V75L 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V75M 2015 PloS one Table HIV V75M 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V75S 2015 PloS one Table HIV V75S 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V75T 2015 PloS one Table HIV V75T 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V82A 2015 PloS one Table HIV V82A 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V82C 2015 PloS one Table HIV V82C 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V82F 2015 PloS one Table HIV V82F 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V82L 2015 PloS one Table HIV V82L 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V82M 2015 PloS one Table HIV V82M 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V82S 2015 PloS one Table HIV V82S 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V82T 2015 PloS one Table HIV V82T 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. V90I 2015 PloS one Table HIV V90I 0 4 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Y115F 2015 PloS one Table HIV Y115F 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Y181C 2015 PloS one Table HIV Y181C 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Y188C 2015 PloS one Table HIV Y188C 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Y188F 2015 PloS one Table HIV Y188F 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Y188H 2015 PloS one Table HIV Y188H 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Y188L 2015 PloS one Table HIV Y188L 0 5 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Y318F 2015 PloS one Table HIV Y318F 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. A421V 2015 PloS one Table HIV A421V 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. A486V 2015 PloS one Table HIV A486V 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. C316N 2015 PloS one Table HIV C316N 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. C316Y/N 2015 PloS one Table HIV C316N;C316Y 0;0 7;7 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. C445F 2015 PloS one Table HIV C445F 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. I482L 2015 PloS one Table HIV I482L 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. I482S/L 2015 PloS one Table HIV I482L;I482S 0;0 7;7 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. L419S 2015 PloS one Table HIV L419S 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. M414T/L 2015 PloS one Table HIV M414L;M414T 0;0 7;7 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. M423T/V 2015 PloS one Table HIV M423T;M423V 0;0 7;7 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. M426A/T 2015 PloS one Table HIV M426A;M426T 0;0 7;7 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. P495L/S 2015 PloS one Table HIV P495L;P495S 0;0 7;7 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. P496S 2015 PloS one Table HIV P496S 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. R422K 2015 PloS one Table HIV R422K 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. S282T 2015 PloS one Table HIV S282T 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. S368T 2015 PloS one Table HIV S368T 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. V494A 2015 PloS one Table HIV V494A 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. V499A 2015 PloS one Table HIV V499A 0 5 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. Y448H/C 2015 PloS one Table HIV Y448C;Y448H 0;0 7;7 26562015 Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. Y452H 2015 PloS one Table HIV Y452H 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. A71V 2015 BMC infectious diseases Table HIV A71V 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. A98G 2015 BMC infectious diseases Table HIV A98G 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. D67E 2015 BMC infectious diseases Table HIV D67E 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. D67N 2015 BMC infectious diseases Table HIV D67N 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. F227L 2015 BMC infectious diseases Table HIV F227L 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. G190A 2015 BMC infectious diseases Table HIV G190A 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. G73S 2015 BMC infectious diseases Table HIV G73S 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. H221Y 2015 BMC infectious diseases Table HIV H221Y 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. I47A 2015 BMC infectious diseases Table HIV I47A 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. I50L 2015 BMC infectious diseases Table HIV I50L 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. I84V 2015 BMC infectious diseases Table HIV I84V 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K101E 2015 BMC infectious diseases Table HIV K101E 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K101H 2015 BMC infectious diseases Table HIV K101H 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K103N 2015 BMC infectious diseases Table HIV K103N 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K20I 2015 BMC infectious diseases Table HIV K20I 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K20T 2015 BMC infectious diseases Table HIV K20T 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K219N 2015 BMC infectious diseases Table HIV K219N 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K219Q 2015 BMC infectious diseases Table HIV K219Q 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K219W 2015 BMC infectious diseases Table HIV K219W 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K65R 2015 BMC infectious diseases Table HIV K65R 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K70R 2015 BMC infectious diseases Table HIV K70R 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. K70T 2015 BMC infectious diseases Table HIV K70T 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. L10F 2015 BMC infectious diseases Table HIV L10F 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. L210W 2015 BMC infectious diseases Table HIV L210W 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. L23I 2015 BMC infectious diseases Table HIV L23I 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. L24I 2015 BMC infectious diseases Table HIV L24I 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. L74I 2015 BMC infectious diseases Table HIV L74I 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. M184V 2015 BMC infectious diseases Table HIV M184V 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. M41L 2015 BMC infectious diseases Table HIV M41L 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. M46I 2015 BMC infectious diseases Table HIV M46I 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. N88S 2015 BMC infectious diseases Table HIV N88S 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. Q58E 2015 BMC infectious diseases Table HIV Q58E 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. T215F 2015 BMC infectious diseases Table HIV T215F 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. T215Y 2015 BMC infectious diseases Table HIV T215Y 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. T69D 2015 BMC infectious diseases Table HIV T69D 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. T74S 2015 BMC infectious diseases Table HIV T74S 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. V106M 2015 BMC infectious diseases Table HIV V106M 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. V108I 2015 BMC infectious diseases Table HIV V108I 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. V75M 2015 BMC infectious diseases Table HIV V75M 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. V82A 2015 BMC infectious diseases Table HIV V82A 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. V90I 2015 BMC infectious diseases Table HIV V90I 0 4 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. Y181C 2015 BMC infectious diseases Table HIV Y181C 0 5 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. Y181V 2015 BMC infectious diseases Table HIV Y181V 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. H221Y 2015 Virology journal Table HIV H221Y 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. K103N 2015 Virology journal Table HIV K103N 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. T215Y 2015 Virology journal Table HIV T215Y 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. V179E 2015 Virology journal Table HIV V179E 0 5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Y181C 2015 Virology journal Table HIV Y181C 0 5 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. T253A 2015 PLoS pathogens Table HIV T253A 0 5 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. W252A 2015 PLoS pathogens Table HIV W252A 0 5 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. E138G 2015 Journal of translational medicine Table HIV E138G 0 5 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. G190A 2015 Journal of translational medicine Table HIV G190A 0 5 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. L10I 2015 Journal of translational medicine Table HIV L10I 0 4 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. T97A 2015 Journal of translational medicine Table HIV T97A 0 4 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. V201I 2015 Journal of translational medicine Table HIV V201I 0 5 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. I54M 2015 Viruses Table HIV I54M 0 4 26633459 Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System. L90M 2015 Viruses Table HIV L90M 0 4 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. A98G 2016 AIDS research and human retroviruses Table HIV A98G 0 4 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. E138A 2016 AIDS research and human retroviruses Table HIV E138A 0 5 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. V106I 2016 AIDS research and human retroviruses Table HIV V106I 0 5 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. V179D 2016 AIDS research and human retroviruses Table HIV V179D 0 5 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. V179E 2016 AIDS research and human retroviruses Table HIV V179E 0 5 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. V179I 2016 AIDS research and human retroviruses Table HIV V179I 0 5 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. V179T 2016 AIDS research and human retroviruses Table HIV V179T 0 5 26651266 Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations. V90I 2016 AIDS research and human retroviruses Table HIV V90I 0 4 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. K20T 2015 BMC bioinformatics Table HIV K20T 0 4 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. L33F 2015 BMC bioinformatics Table HIV L33F 0 4 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. V77I 2015 BMC bioinformatics Table HIV V77I 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. I47A 2015 PloS one Table HIV I47A 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. I47V 2015 PloS one Table HIV I47V 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. I50V 2015 PloS one Table HIV I50V 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. I54M 2015 PloS one Table HIV I54M 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. I54V 2015 PloS one Table HIV I54V 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. I84V 2015 PloS one Table HIV I84V 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. L76V 2015 PloS one Table HIV L76V 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. L90M 2015 PloS one Table HIV L90M 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. M46I 2015 PloS one Table HIV M46I 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V32I 2015 PloS one Table HIV V32I 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V82A 2015 PloS one Table HIV V82A 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V82F 2015 PloS one Table HIV V82F 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V82M 2015 PloS one Table HIV V82M 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V82S 2015 PloS one Table HIV V82S 0 4 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. V82T 2015 PloS one Table HIV V82T 0 4 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. A502F 2016 PloS one Table HIV A502F 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. A508V 2016 PloS one Table HIV A508V 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. E224A 2016 PloS one Table HIV E224A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. F227A 2016 PloS one Table HIV F227A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. G231A 2016 PloS one Table HIV G231A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. K103N 2016 PloS one Table HIV K103N 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. L228A 2016 PloS one Table HIV L228A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. M230A 2016 PloS one Table HIV M230A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. N474A 2016 PloS one Table HIV N474A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. P225A 2016 PloS one Table HIV P225A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. P226A 2016 PloS one Table HIV P226A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. V106A 2016 PloS one Table HIV V106A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. V108A 2016 PloS one Table HIV V108A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. W229A 2016 PloS one Table HIV W229A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Y181C 2016 PloS one Table HIV Y181C 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Y188A 2016 PloS one Table HIV Y188A 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Y188L 2016 PloS one Table HIV Y188L 0 5 26800261 Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6. Y501A 2016 PloS one Table HIV Y501A 0 5 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. G190S/A 2016 PloS one Table HIV G190A;G190S 0;0 7;7 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. K103N 2016 PloS one Table HIV K103N 0 5 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. M184V/I 2016 PloS one Table HIV M184I;M184V 0;0 7;7 26828876 Prevalence of Primary HIV Drug Resistance in Thailand Detected by Short Reverse Transcriptase Genotypic Resistance Assay. Y181C/I 2016 PloS one Table HIV Y181C;Y181I 0;0 7;7 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. A71I 2016 Frontiers in microbiology Table HIV A71I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. A71T 2016 Frontiers in microbiology Table HIV A71T 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. A71V 2016 Frontiers in microbiology Table HIV A71V 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. D30N 2016 Frontiers in microbiology Table HIV D30N 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. F53L 2016 Frontiers in microbiology Table HIV F53L 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. G16E 2016 Frontiers in microbiology Table HIV G16E 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. G57R 2016 Frontiers in microbiology Table HIV G57R 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. G73S 2016 Frontiers in microbiology Table HIV G73S 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. G73T 2016 Frontiers in microbiology Table HIV G73T 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. H69K 2016 Frontiers in microbiology Table HIV H69K 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. H69R 2016 Frontiers in microbiology Table HIV H69R 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. I54V 2016 Frontiers in microbiology Table HIV I54V 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. I62V 2016 Frontiers in microbiology Table HIV I62V 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. I84V 2016 Frontiers in microbiology Table HIV I84V 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. I93L 2016 Frontiers in microbiology Table HIV I93L 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. K20I 2016 Frontiers in microbiology Table HIV K20I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. K20R 2016 Frontiers in microbiology Table HIV K20R 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. K20T 2016 Frontiers in microbiology Table HIV K20T 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. K43T 2016 Frontiers in microbiology Table HIV K43T 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L10I 2016 Frontiers in microbiology Table HIV L10I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L10V 2016 Frontiers in microbiology Table HIV L10V 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L23I 2016 Frontiers in microbiology Table HIV L23I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L24I 2016 Frontiers in microbiology Table HIV L24I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L33F 2016 Frontiers in microbiology Table HIV L33F 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L33I 2016 Frontiers in microbiology Table HIV L33I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L63P 2016 Frontiers in microbiology Table HIV L63P 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L63T 2016 Frontiers in microbiology Table HIV L63T 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. L90M 2016 Frontiers in microbiology Table HIV L90M 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. M36I 2016 Frontiers in microbiology Table HIV M36I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. M36L 2016 Frontiers in microbiology Table HIV M36L 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. M36V 2016 Frontiers in microbiology Table HIV M36V 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. M46I 2016 Frontiers in microbiology Table HIV M46I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. M46L 2016 Frontiers in microbiology Table HIV M46L 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. N88D 2016 Frontiers in microbiology Table HIV N88D 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. Q58E 2016 Frontiers in microbiology Table HIV Q58E 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. V32I 2016 Frontiers in microbiology Table HIV V32I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. V77I 2016 Frontiers in microbiology Table HIV V77I 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. V82A 2016 Frontiers in microbiology Table HIV V82A 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. V82F 2016 Frontiers in microbiology Table HIV V82F 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. V82M 2016 Frontiers in microbiology Table HIV V82M 0 4 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. V82S 2016 Frontiers in microbiology Table HIV V82S 0 4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. G48V 2016 PloS one Table HIV G48V 0 4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. I54V 2016 PloS one Table HIV I54V 0 4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. I84V 2016 PloS one Table HIV I84V 0 4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. M46I 2016 PloS one Table HIV M46I 0 4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. N88S 2016 PloS one Table HIV N88S 0 4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. V82A 2016 PloS one Table HIV V82A 0 4 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. V82T 2016 PloS one Table HIV V82T 0 4 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. G140S 2016 AIDS research and human retroviruses Table HIV G140S 0 5 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Q148H 2016 AIDS research and human retroviruses Table HIV Q148H 0 5 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Q148N 2016 AIDS research and human retroviruses Table HIV Q148N 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. D67G 2016 PloS one Table HIV D67G 0 4 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. F227L 2016 PloS one Table HIV F227L 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. G190A 2016 PloS one Table HIV G190A 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. G190C 2016 PloS one Table HIV G190C 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. H221Y 2016 PloS one Table HIV H221Y 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. K101E 2016 PloS one Table HIV K101E 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. K101E/Q 2016 PloS one Table HIV K101E;K101Q 0;0 7;7 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. K103N 2016 PloS one Table HIV K103N 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. K103N/S 2016 PloS one Table HIV K103N;K103S 0;0 7;7 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. K238N 2016 PloS one Table HIV K238N 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. K65R 2016 PloS one Table HIV K65R 0 4 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. K70E 2016 PloS one Table HIV K70E 0 4 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. L210W 2016 PloS one Table HIV L210W 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. M184I 2016 PloS one Table HIV M184I 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. M184V 2016 PloS one Table HIV M184V 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. M41L 2016 PloS one Table HIV M41L 0 4 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. T215F/Y 2016 PloS one Table HIV T215F;T215Y 0;0 7;7 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. V106M 2016 PloS one Table HIV V106M 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. V179D 2016 PloS one Table HIV V179D 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. V75L 2016 PloS one Table HIV V75L 0 4 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. V90I 2016 PloS one Table HIV V90I 0 4 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. Y115F 2016 PloS one Table HIV Y115F 0 5 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. Y181C 2016 PloS one Table HIV Y181C 0 5 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. H51Y 2016 Retrovirology Table HIV H51Y 0 4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. R263K 2016 Retrovirology Table HIV R263K 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. A124N 2016 BMC infectious diseases Table HIV A124N 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. A124T 2016 BMC infectious diseases Table HIV A124T 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. C130Y 2016 BMC infectious diseases Table HIV C130Y 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. C56S 2016 BMC infectious diseases Table HIV C56S 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. D55Y 2016 BMC infectious diseases Table HIV D55Y 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. E157A 2016 BMC infectious diseases Table HIV E157A 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. E96D 2016 BMC infectious diseases Table HIV E96D 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. G123S 2016 BMC infectious diseases Table HIV G123S 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. G134E 2016 BMC infectious diseases Table HIV G134E 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. G52P 2016 BMC infectious diseases Table HIV G52P 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. H171Q 2016 BMC infectious diseases Table HIV H171Q 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. I113V 2016 BMC infectious diseases Table HIV I113V 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. I161X 2016 BMC infectious diseases Table HIV I161X 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. K103R 2016 BMC infectious diseases Table HIV K103R 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. K111T 2016 BMC infectious diseases Table HIV K111T 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. K156N 2016 BMC infectious diseases Table HIV K156N 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. L101I 2016 BMC infectious diseases Table HIV L101I 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. L68R 2016 BMC infectious diseases Table HIV L68R 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. L74I 2016 BMC infectious diseases Table HIV L74I 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. M50I 2016 BMC infectious diseases Table HIV M50I 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. M50V 2016 BMC infectious diseases Table HIV M50V 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. N155H 2016 BMC infectious diseases Table HIV N155H 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. S119P 2016 BMC infectious diseases Table HIV S119P 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. S119R 2016 BMC infectious diseases Table HIV S119R 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. T122I 2016 BMC infectious diseases Table HIV T122I 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. T125A 2016 BMC infectious diseases Table HIV T125A 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. T97A 2016 BMC infectious diseases Table HIV T97A 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. V150A 2016 BMC infectious diseases Table HIV V150A 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. V151I 2016 BMC infectious diseases Table HIV V151I 0 5 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. V71I 2016 BMC infectious diseases Table HIV V71I 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. V72I 2016 BMC infectious diseases Table HIV V72I 0 4 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. Y99C 2016 BMC infectious diseases Table HIV Y99C 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. A62V 2016 Journal of the International AIDS Society Table HIV A62V 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. A98G 2016 Journal of the International AIDS Society Table HIV A98G 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. D67G 2016 Journal of the International AIDS Society Table HIV D67G 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. D67N 2016 Journal of the International AIDS Society Table HIV D67N 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. E138Q 2016 Journal of the International AIDS Society Table HIV E138Q 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. G190A 2016 Journal of the International AIDS Society Table HIV G190A 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. G190S 2016 Journal of the International AIDS Society Table HIV G190S 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. H221Y 2016 Journal of the International AIDS Society Table HIV H221Y 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K101E 2016 Journal of the International AIDS Society Table HIV K101E 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K101P 2016 Journal of the International AIDS Society Table HIV K101P 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K103N 2016 Journal of the International AIDS Society Table HIV K103N 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K103S 2016 Journal of the International AIDS Society Table HIV K103S 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K219E 2016 Journal of the International AIDS Society Table HIV K219E 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K65R 2016 Journal of the International AIDS Society Table HIV K65R 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K70E 2016 Journal of the International AIDS Society Table HIV K70E 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K70Q 2016 Journal of the International AIDS Society Table HIV K70Q 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K70R 2016 Journal of the International AIDS Society Table HIV K70R 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K70T 2016 Journal of the International AIDS Society Table HIV K70T 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. L100I 2016 Journal of the International AIDS Society Table HIV L100I 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. L74V 2016 Journal of the International AIDS Society Table HIV L74V 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. M184I 2016 Journal of the International AIDS Society Table HIV M184I 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. M184V 2016 Journal of the International AIDS Society Table HIV M184V 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. M230L 2016 Journal of the International AIDS Society Table HIV M230L 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. M41L 2016 Journal of the International AIDS Society Table HIV M41L 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. V106A 2016 Journal of the International AIDS Society Table HIV V106A 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. V106M 2016 Journal of the International AIDS Society Table HIV V106M 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. V108I 2016 Journal of the International AIDS Society Table HIV V108I 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. V179F 2016 Journal of the International AIDS Society Table HIV V179F 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. V75M 2016 Journal of the International AIDS Society Table HIV V75M 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. V90I 2016 Journal of the International AIDS Society Table HIV V90I 0 4 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Y115F 2016 Journal of the International AIDS Society Table HIV Y115F 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Y181C 2016 Journal of the International AIDS Society Table HIV Y181C 0 5 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Y181G 2016 Journal of the International AIDS Society Table HIV Y181G 0 5 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. A77P 2016 FEBS open bio Table HIV A77P 0 4 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. A78V 2016 FEBS open bio Table HIV A78V 0 4 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. L189F 2016 FEBS open bio Table HIV L189F 0 5 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. L189I 2016 FEBS open bio Table HIV L189I 0 5 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. L189P 2016 FEBS open bio Table HIV L189P 0 5 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. W23A 2016 FEBS open bio Table HIV W23A 0 4 27576440 HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. S332N 2016 Retrovirology Table HIV S332N 0 5 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. S40A 2016 Retrovirology Table HIV S40A 0 4 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. S40F 2016 Retrovirology Table HIV S40F 0 4 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. L188F 2016 Retrovirology Table HIV L188F 0 5 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Q182S 2016 Retrovirology Table HIV Q182S 0 5 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. M50I 2016 Antimicrobial agents and chemotherapy Table HIV M50I 0 4 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. S119R 2016 Antimicrobial agents and chemotherapy Table HIV S119R 0 5 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. S153Y 2016 Antimicrobial agents and chemotherapy Table HIV S153Y 0 5 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. G140S 2016 Retrovirology Table HIV G140S 0 5 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. N155H 2016 Retrovirology Table HIV N155H 0 5 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. Q148H 2016 Retrovirology Table HIV Q148H 0 5 27682062 Drug resistant integrase mutants cause aberrant HIV integrations. Y143R 2016 Retrovirology Table HIV Y143R 0 5 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. E12A 2016 PloS one Table HIV E12A 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. A62V 2016 BMC research notes Table HIV A62V 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. A71T 2016 BMC research notes Table HIV A71T 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. A98G 2016 BMC research notes Table HIV A98G 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. G190A 2016 BMC research notes Table HIV G190A 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. I47V 2016 BMC research notes Table HIV I47V 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. I54V 2016 BMC research notes Table HIV I54V 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. K101E 2016 BMC research notes Table HIV K101E 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. K103N 2016 BMC research notes Table HIV K103N 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. K20T 2016 BMC research notes Table HIV K20T 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. K219E 2016 BMC research notes Table HIV K219E 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. K43T 2016 BMC research notes Table HIV K43T 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. K65R 2016 BMC research notes Table HIV K65R 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. K70R 2016 BMC research notes Table HIV K70R 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L100I 2016 BMC research notes Table HIV L100I 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L10F 2016 BMC research notes Table HIV L10F 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L10I 2016 BMC research notes Table HIV L10I 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L10V 2016 BMC research notes Table HIV L10V 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L210W 2016 BMC research notes Table HIV L210W 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L24I 2016 BMC research notes Table HIV L24I 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L33F 2016 BMC research notes Table HIV L33F 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L33I 2016 BMC research notes Table HIV L33I 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L74V 2016 BMC research notes Table HIV L74V 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. L89V 2016 BMC research notes Table HIV L89V 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. M184L 2016 BMC research notes Table HIV M184L 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. M184V 2016 BMC research notes Table HIV M184V 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. M41L 2016 BMC research notes Table HIV M41L 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. M46I 2016 BMC research notes Table HIV M46I 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. M46I/L 2016 BMC research notes Table HIV M46I;M46L 0;0 6;6 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. M46L 2016 BMC research notes Table HIV M46L 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. Q58E 2016 BMC research notes Table HIV Q58E 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. T215A 2016 BMC research notes Table HIV T215A 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. T215C 2016 BMC research notes Table HIV T215C 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. T215Y 2016 BMC research notes Table HIV T215Y 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. V82A 2016 BMC research notes Table HIV V82A 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. V82A/S 2016 BMC research notes Table HIV V82A;V82S 0;0 6;6 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. V82F 2016 BMC research notes Table HIV V82F 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. V82S 2016 BMC research notes Table HIV V82S 0 4 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. Y181C 2016 BMC research notes Table HIV Y181C 0 5 28010730 From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults. Y181F 2016 BMC research notes Table HIV Y181F 0 5 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. D67N 2017 AIDS research and therapy Table HIV D67N 0 4 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. K65R 2017 AIDS research and therapy Table HIV K65R 0 4 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. K70E 2017 AIDS research and therapy Table HIV K70E 0 4 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. K70R 2017 AIDS research and therapy Table HIV K70R 0 4 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. L100I 2017 AIDS research and therapy Table HIV L100I 0 5 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. L210W 2017 AIDS research and therapy Table HIV L210W 0 5 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. L74V 2017 AIDS research and therapy Table HIV L74V 0 4 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. M230L 2017 AIDS research and therapy Table HIV M230L 0 5 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. M41L 2017 AIDS research and therapy Table HIV M41L 0 4 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. Y115F 2017 AIDS research and therapy Table HIV Y115F 0 5 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. E283A 2016 Pharmacology research & perspectives Table HIV E283A 0 5 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. G286F 2016 Pharmacology research & perspectives Table HIV G286F 0 5 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. L203F 2016 Pharmacology research & perspectives Table HIV L203F 0 5 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. W248A 2016 Pharmacology research & perspectives Table HIV W248A 0 5 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Y244A 2016 Pharmacology research & perspectives Table HIV Y244A 0 5 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Y251A 2016 Pharmacology research & perspectives Table HIV Y251A 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. A158S 2017 PloS one Table HIV A158S 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. A62V 2017 PloS one Table HIV A62V 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. D123E 2017 PloS one Table HIV D123E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. D177N 2017 PloS one Table HIV D177N 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. D218E 2017 PloS one Table HIV D218E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. D237E 2017 PloS one Table HIV D237E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. D67N 2017 PloS one Table HIV D67N 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. D67S 2017 PloS one Table HIV D67S 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E169D 2017 PloS one Table HIV E169D 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E203D 2017 PloS one Table HIV E203D 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E203K 2017 PloS one Table HIV E203K 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E203R 2017 PloS one Table HIV E203R 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E224D 2017 PloS one Table HIV E224D 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E35D 2017 PloS one Table HIV E35D 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E40R 2017 PloS one Table HIV E40R 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. E44A 2017 PloS one Table HIV E44A 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. F227L 2017 PloS one Table HIV F227L 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. G112S 2017 PloS one Table HIV G112S 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. G190A 2017 PloS one Table HIV G190A 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. G190S 2017 PloS one Table HIV G190S 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. G196E 2017 PloS one Table HIV G196E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. H221Y 2017 PloS one Table HIV H221Y 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. I202V 2017 PloS one Table HIV I202V 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. I93L 2017 PloS one Table HIV I93L 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K101E 2017 PloS one Table HIV K101E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K101Q 2017 PloS one Table HIV K101Q 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K103H 2017 PloS one Table HIV K103H 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K103N 2017 PloS one Table HIV K103N 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K103S 2017 PloS one Table HIV K103S 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K166R 2017 PloS one Table HIV K166R 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K219E 2017 PloS one Table HIV K219E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K219H 2017 PloS one Table HIV K219H 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K219Q 2017 PloS one Table HIV K219Q 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K223E 2017 PloS one Table HIV K223E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K43E 2017 PloS one Table HIV K43E 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K46Q 2017 PloS one Table HIV K46Q 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K65R 2017 PloS one Table HIV K65R 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K70G 2017 PloS one Table HIV K70G 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. K70R 2017 PloS one Table HIV K70R 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. L210W 2017 PloS one Table HIV L210W 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. L228R 2017 PloS one Table HIV L228R 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. L74I 2017 PloS one Table HIV L74I 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. L74V 2017 PloS one Table HIV L74V 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. M184V 2017 PloS one Table HIV M184V 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. M41L 2017 PloS one Table HIV M41L 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. P225H 2017 PloS one Table HIV P225H 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Q151M 2017 PloS one Table HIV Q151M 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Q18H 2017 PloS one Table HIV Q18H 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Q197K 2017 PloS one Table HIV Q197K 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. R211G 2017 PloS one Table HIV R211G 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. R211K 2017 PloS one Table HIV R211K 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. S162D 2017 PloS one Table HIV S162D 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. S162H 2017 PloS one Table HIV S162H 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. S37N 2017 PloS one Table HIV S37N 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. S68G 2017 PloS one Table HIV S68G 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. S68N 2017 PloS one Table HIV S68N 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. T200E 2017 PloS one Table HIV T200E 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. T200V 2017 PloS one Table HIV T200V 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. T215F 2017 PloS one Table HIV T215F 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. T215I 2017 PloS one Table HIV T215I 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. T215Y 2017 PloS one Table HIV T215Y 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. T39A 2017 PloS one Table HIV T39A 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V106A 2017 PloS one Table HIV V106A 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V108I 2017 PloS one Table HIV V108I 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V118I 2017 PloS one Table HIV V118I 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V179I 2017 PloS one Table HIV V179I 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V35L 2017 PloS one Table HIV V35L 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V35R 2017 PloS one Table HIV V35R 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V75S 2017 PloS one Table HIV V75S 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V75T 2017 PloS one Table HIV V75T 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. V90I 2017 PloS one Table HIV V90I 0 4 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Y181C 2017 PloS one Table HIV Y181C 0 5 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Y188L 2017 PloS one Table HIV Y188L 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. A98G 2017 AIDS research and therapy Table HIV A98G 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. D67N 2017 AIDS research and therapy Table HIV D67N 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. E138A 2017 AIDS research and therapy Table HIV E138A 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. E138G 2017 AIDS research and therapy Table HIV E138G 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. E138K 2017 AIDS research and therapy Table HIV E138K 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. E138Q 2017 AIDS research and therapy Table HIV E138Q 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. F227L 2017 AIDS research and therapy Table HIV F227L 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. G190A 2017 AIDS research and therapy Table HIV G190A 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. G190A/S 2017 AIDS research and therapy Table HIV G190A;G190S 0;0 7;7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. G190R 2017 AIDS research and therapy Table HIV G190R 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. G190S 2017 AIDS research and therapy Table HIV G190S 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. H221Y 2017 AIDS research and therapy Table HIV H221Y 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K101E 2017 AIDS research and therapy Table HIV K101E 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K103N 2017 AIDS research and therapy Table HIV K103N 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K103N/S 2017 AIDS research and therapy Table HIV K103N;K103S 0;0 7;7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K103S 2017 AIDS research and therapy Table HIV K103S 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K103T 2017 AIDS research and therapy Table HIV K103T 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K219E 2017 AIDS research and therapy Table HIV K219E 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K219Q 2017 AIDS research and therapy Table HIV K219Q 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K238T 2017 AIDS research and therapy Table HIV K238T 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K65R 2017 AIDS research and therapy Table HIV K65R 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. K70R 2017 AIDS research and therapy Table HIV K70R 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. L210W 2017 AIDS research and therapy Table HIV L210W 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. L74I 2017 AIDS research and therapy Table HIV L74I 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. L74I/V 2017 AIDS research and therapy Table HIV L74I;L74V 0;0 6;6 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. L74V 2017 AIDS research and therapy Table HIV L74V 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. M184V 2017 AIDS research and therapy Table HIV M184V 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. M184V/I 2017 AIDS research and therapy Table HIV M184I;M184V 0;0 7;7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. M230I 2017 AIDS research and therapy Table HIV M230I 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. M230L 2017 AIDS research and therapy Table HIV M230L 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. M230L/I 2017 AIDS research and therapy Table HIV M230I;M230L 0;0 7;7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. M41L 2017 AIDS research and therapy Table HIV M41L 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. P225H 2017 AIDS research and therapy Table HIV P225H 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. T215F 2017 AIDS research and therapy Table HIV T215F 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. T215I 2017 AIDS research and therapy Table HIV T215I 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. T215Y 2017 AIDS research and therapy Table HIV T215Y 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. T215Y/F 2017 AIDS research and therapy Table HIV T215F;T215Y 0;0 7;7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. T69N 2017 AIDS research and therapy Table HIV T69N 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V106A 2017 AIDS research and therapy Table HIV V106A 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V106A/M 2017 AIDS research and therapy Table HIV V106A;V106M 0;0 7;7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V106I 2017 AIDS research and therapy Table HIV V106I 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V106M 2017 AIDS research and therapy Table HIV V106M 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V108I 2017 AIDS research and therapy Table HIV V108I 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V179E 2017 AIDS research and therapy Table HIV V179E 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V75M 2017 AIDS research and therapy Table HIV V75M 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. V90I 2017 AIDS research and therapy Table HIV V90I 0 4 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Y181C 2017 AIDS research and therapy Table HIV Y181C 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Y188C 2017 AIDS research and therapy Table HIV Y188C 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Y188L 2017 AIDS research and therapy Table HIV Y188L 0 5 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Y188L/C 2017 AIDS research and therapy Table HIV Y188C;Y188L 0;0 7;7 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Y188W 2017 AIDS research and therapy Table HIV Y188W 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. A62V 2017 PloS one Table HIV A62V 0 4 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. E138A 2017 PloS one Table HIV E138A 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. G190A 2017 PloS one Table HIV G190A 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. K101H 2017 PloS one Table HIV K101H 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. K103N 2017 PloS one Table HIV K103N 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. K103S 2017 PloS one Table HIV K103S 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. K219N 2017 PloS one Table HIV K219N 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. K65R 2017 PloS one Table HIV K65R 0 4 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. L210W 2017 PloS one Table HIV L210W 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. M184V 2017 PloS one Table HIV M184V 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. V106M 2017 PloS one Table HIV V106M 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. V11I 2017 PloS one Table HIV V11I 0 4 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. V75I 2017 PloS one Table HIV V75I 0 4 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. V90I 2017 PloS one Table HIV V90I 0 4 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. Y181C 2017 PloS one Table HIV Y181C 0 5 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. T97A 2017 PloS one Table HIV T97A 0 4 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. K103N 2017 Clinical infectious diseases Table HIV K103N 0 5 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. K277R 2017 Nucleic acids research Table HIV K277R 0 5 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. R277K 2017 Nucleic acids research Table HIV R277K 0 5 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. K65R 2017 The Journal of antimicrobial chemotherapy Table HIV K65R 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. A124T 2017 The Journal of antimicrobial chemotherapy Table HIV A124T 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. A21T 2017 The Journal of antimicrobial chemotherapy Table HIV A21T 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. A23V 2017 The Journal of antimicrobial chemotherapy Table HIV A23V 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. A265V 2017 The Journal of antimicrobial chemotherapy Table HIV A265V 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. D207N 2017 The Journal of antimicrobial chemotherapy Table HIV D207N 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. D232E 2017 The Journal of antimicrobial chemotherapy Table HIV D232E 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. D256E 2017 The Journal of antimicrobial chemotherapy Table HIV D256E 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. D25E 2017 The Journal of antimicrobial chemotherapy Table HIV D25E 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. D278E 2017 The Journal of antimicrobial chemotherapy Table HIV D278E 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. D278N 2017 The Journal of antimicrobial chemotherapy Table HIV D278N 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. D286N 2017 The Journal of antimicrobial chemotherapy Table HIV D286N 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. E11D 2017 The Journal of antimicrobial chemotherapy Table HIV E11D 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. E13D 2017 The Journal of antimicrobial chemotherapy Table HIV E13D 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. F181L 2017 The Journal of antimicrobial chemotherapy Table HIV F181L 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. G163E 2017 The Journal of antimicrobial chemotherapy Table HIV G163E 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. G190A 2017 The Journal of antimicrobial chemotherapy Table HIV G190A 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. G193E 2017 The Journal of antimicrobial chemotherapy Table HIV G193E 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. I113V 2017 The Journal of antimicrobial chemotherapy Table HIV I113V 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. I203M 2017 The Journal of antimicrobial chemotherapy Table HIV I203M 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. I220L 2017 The Journal of antimicrobial chemotherapy Table HIV I220L 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. I72V 2017 The Journal of antimicrobial chemotherapy Table HIV I72V 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. I73V 2017 The Journal of antimicrobial chemotherapy Table HIV I73V 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. I84V 2017 The Journal of antimicrobial chemotherapy Table HIV I84V 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. K111E 2017 The Journal of antimicrobial chemotherapy Table HIV K111E 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. K111Q 2017 The Journal of antimicrobial chemotherapy Table HIV K111Q 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. K136Q 2017 The Journal of antimicrobial chemotherapy Table HIV K136Q 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. K211Q 2017 The Journal of antimicrobial chemotherapy Table HIV K211Q 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. K244R 2017 The Journal of antimicrobial chemotherapy Table HIV K244R 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. L101I 2017 The Journal of antimicrobial chemotherapy Table HIV L101I 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. L234I 2017 The Journal of antimicrobial chemotherapy Table HIV L234I 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. L28I 2017 The Journal of antimicrobial chemotherapy Table HIV L28I 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. L45Q 2017 The Journal of antimicrobial chemotherapy Table HIV L45Q 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. L45R 2017 The Journal of antimicrobial chemotherapy Table HIV L45R 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. M154I 2017 The Journal of antimicrobial chemotherapy Table HIV M154I 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. M50I 2017 The Journal of antimicrobial chemotherapy Table HIV M50I 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. N232D 2017 The Journal of antimicrobial chemotherapy Table HIV N232D 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. N254H 2017 The Journal of antimicrobial chemotherapy Table HIV N254H 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. R127K 2017 The Journal of antimicrobial chemotherapy Table HIV R127K 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. R20K 2017 The Journal of antimicrobial chemotherapy Table HIV R20K 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S119G 2017 The Journal of antimicrobial chemotherapy Table HIV S119G 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S119P 2017 The Journal of antimicrobial chemotherapy Table HIV S119P 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S119T 2017 The Journal of antimicrobial chemotherapy Table HIV S119T 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S17N 2017 The Journal of antimicrobial chemotherapy Table HIV S17N 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S230N 2017 The Journal of antimicrobial chemotherapy Table HIV S230N 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S24D 2017 The Journal of antimicrobial chemotherapy Table HIV S24D 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S255Q 2017 The Journal of antimicrobial chemotherapy Table HIV S255Q 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S283G 2017 The Journal of antimicrobial chemotherapy Table HIV S283G 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S39C 2017 The Journal of antimicrobial chemotherapy Table HIV S39C 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. S39N 2017 The Journal of antimicrobial chemotherapy Table HIV S39N 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T112M 2017 The Journal of antimicrobial chemotherapy Table HIV T112M 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T112V 2017 The Journal of antimicrobial chemotherapy Table HIV T112V 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T122I 2017 The Journal of antimicrobial chemotherapy Table HIV T122I 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T124A 2017 The Journal of antimicrobial chemotherapy Table HIV T124A 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T124N 2017 The Journal of antimicrobial chemotherapy Table HIV T124N 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T125A 2017 The Journal of antimicrobial chemotherapy Table HIV T125A 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T125V 2017 The Journal of antimicrobial chemotherapy Table HIV T125V 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T206S 2017 The Journal of antimicrobial chemotherapy Table HIV T206S 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. T218I 2017 The Journal of antimicrobial chemotherapy Table HIV T218I 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. V201I 2017 The Journal of antimicrobial chemotherapy Table HIV V201I 0 5 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. V31I 2017 The Journal of antimicrobial chemotherapy Table HIV V31I 0 4 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Y227F 2017 The Journal of antimicrobial chemotherapy Table HIV Y227F 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. E138A 2017 PloS one Table HIV E138A 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. E138G 2017 PloS one Table HIV E138G 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. G190E 2017 PloS one Table HIV G190E 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. K103R 2017 PloS one Table HIV K103R 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. K219R 2017 PloS one Table HIV K219R 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. K238N 2017 PloS one Table HIV K238N 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. K43T 2017 PloS one Table HIV K43T 0 4 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. K70Q 2017 PloS one Table HIV K70Q 0 4 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. L23I 2017 PloS one Table HIV L23I 0 4 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. M46I 2017 PloS one Table HIV M46I 0 4 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. Q58E 2017 PloS one Table HIV Q58E 0 4 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. V179D 2017 PloS one Table HIV V179D 0 5 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. V179E 2017 PloS one Table HIV V179E 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. D207A 2017 Scientific reports Table HIV D207A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. E212A 2017 Scientific reports Table HIV E212A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. K211A 2017 Scientific reports Table HIV K211A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. K215A 2017 Scientific reports Table HIV K215A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. K219A 2017 Scientific reports Table HIV K219A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. L213A 2017 Scientific reports Table HIV L213A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. Q209A 2017 Scientific reports Table HIV Q209A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. T206A 2017 Scientific reports Table HIV T206A 0 5 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. T210A 2017 Scientific reports Table HIV T210A 0 5 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. S75X 2017 Scientific reports Table HIV S75X 0 4 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. A71T 2017 PloS one Table HIV A71T 0 4 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. D67N 2017 PloS one Table HIV D67N 0 4 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. G190A 2017 PloS one Table HIV G190A 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. H221Y 2017 PloS one Table HIV H221Y 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. K101E 2017 PloS one Table HIV K101E 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. K103N 2017 PloS one Table HIV K103N 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. L10I 2017 PloS one Table HIV L10I 0 4 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. L210W 2017 PloS one Table HIV L210W 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. M184V 2017 PloS one Table HIV M184V 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. M41L 2017 PloS one Table HIV M41L 0 4 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. Q151M 2017 PloS one Table HIV Q151M 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. T215F 2017 PloS one Table HIV T215F 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. T215Y 2017 PloS one Table HIV T215Y 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. T69N 2017 PloS one Table HIV T69N 0 4 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. V106I 2017 PloS one Table HIV V106I 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. V108I 2017 PloS one Table HIV V108I 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. V118I 2017 PloS one Table HIV V118I 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. V179D 2017 PloS one Table HIV V179D 0 5 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. Y181C 2017 PloS one Table HIV Y181C 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. A62V 2017 AIDS research and therapy Table HIV A62V 0 4 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. D67N 2017 AIDS research and therapy Table HIV D67N 0 4 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. G190A 2017 AIDS research and therapy Table HIV G190A 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. K103N 2017 AIDS research and therapy Table HIV K103N 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. K219Q/E 2017 AIDS research and therapy Table HIV K219E;K219Q 0;0 7;7 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. K65R 2017 AIDS research and therapy Table HIV K65R 0 4 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. K70R 2017 AIDS research and therapy Table HIV K70R 0 4 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. L100I 2017 AIDS research and therapy Table HIV L100I 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. L74V 2017 AIDS research and therapy Table HIV L74V 0 4 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. M184V 2017 AIDS research and therapy Table HIV M184V 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. M41L 2017 AIDS research and therapy Table HIV M41L 0 4 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Q151M 2017 AIDS research and therapy Table HIV Q151M 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. T215Y 2017 AIDS research and therapy Table HIV T215Y 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. V108I 2017 AIDS research and therapy Table HIV V108I 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. V75I/S 2017 AIDS research and therapy Table HIV V75I;V75S 0;0 6;6 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Y115F 2017 AIDS research and therapy Table HIV Y115F 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Y181C 2017 AIDS research and therapy Table HIV Y181C 0 5 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Y188L/H 2017 AIDS research and therapy Table HIV Y188H;Y188L 0;0 7;7 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. D30N 2017 Journal of the International AIDS Society Table HIV D30N 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. D67N 2017 Journal of the International AIDS Society Table HIV D67N 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. F77L 2017 Journal of the International AIDS Society Table HIV F77L 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. G190E 2017 Journal of the International AIDS Society Table HIV G190E 0 5 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. I50L 2017 Journal of the International AIDS Society Table HIV I50L 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. I85V 2017 Journal of the International AIDS Society Table HIV I85V 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. K101E 2017 Journal of the International AIDS Society Table HIV K101E 0 5 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. K103N 2017 Journal of the International AIDS Society Table HIV K103N 0 5 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. K65R 2017 Journal of the International AIDS Society Table HIV K65R 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. K70E 2017 Journal of the International AIDS Society Table HIV K70E 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. M184V 2017 Journal of the International AIDS Society Table HIV M184V 0 5 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. M46I 2017 Journal of the International AIDS Society Table HIV M46I 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. M46L 2017 Journal of the International AIDS Society Table HIV M46L 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. N83D 2017 Journal of the International AIDS Society Table HIV N83D 0 4 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. T215S 2017 Journal of the International AIDS Society Table HIV T215S 0 5 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Y188C 2017 Journal of the International AIDS Society Table HIV Y188C 0 5 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. Ser46Phe 2017 Frontiers in microbiology Table HIV S46F 0 8 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. D67N 2017 Iranian journal of public health Table HIV D67N 0 4 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. F227L 2017 Iranian journal of public health Table HIV F227L 0 5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. K101E 2017 Iranian journal of public health Table HIV K101E 0 5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. K103N 2017 Iranian journal of public health Table HIV K103N 0 5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. L210W 2017 Iranian journal of public health Table HIV L210W 0 5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. L90M 2017 Iranian journal of public health Table HIV L90M 0 4 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. M184V 2017 Iranian journal of public health Table HIV M184V 0 5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. M41L 2017 Iranian journal of public health Table HIV M41L 0 4 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. M46I 2017 Iranian journal of public health Table HIV M46I 0 4 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. V179F 2017 Iranian journal of public health Table HIV V179F 0 5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. Y181C 2017 Iranian journal of public health Table HIV Y181C 0 5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. Y188L 2017 Iranian journal of public health Table HIV Y188L 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. D67N 2017 PloS one Table HIV D67N 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. E138K 2017 PloS one Table HIV E138K 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. E44A 2017 PloS one Table HIV E44A 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. F227L 2017 PloS one Table HIV F227L 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. G190A 2017 PloS one Table HIV G190A 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. G190E 2017 PloS one Table HIV G190E 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. H221Y 2017 PloS one Table HIV H221Y 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K101E 2017 PloS one Table HIV K101E 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K101Q 2017 PloS one Table HIV K101Q 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K103N 2017 PloS one Table HIV K103N 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K219E 2017 PloS one Table HIV K219E 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K219Q 2017 PloS one Table HIV K219Q 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K238T 2017 PloS one Table HIV K238T 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K65R 2017 PloS one Table HIV K65R 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K70E 2017 PloS one Table HIV K70E 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. K70R 2017 PloS one Table HIV K70R 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. L100I 2017 PloS one Table HIV L100I 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. L210W 2017 PloS one Table HIV L210W 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. L74I 2017 PloS one Table HIV L74I 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. M184I 2017 PloS one Table HIV M184I 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. M184V 2017 PloS one Table HIV M184V 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. M41L 2017 PloS one Table HIV M41L 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. P225H 2017 PloS one Table HIV P225H 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. T215I 2017 PloS one Table HIV T215I 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. T215V 2017 PloS one Table HIV T215V 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. T215Y 2017 PloS one Table HIV T215Y 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. T69D 2017 PloS one Table HIV T69D 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. T69Q 2017 PloS one Table HIV T69Q 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V106A 2017 PloS one Table HIV V106A 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V106M 2017 PloS one Table HIV V106M 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V106V 2017 PloS one Table HIV V106V 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V118I 2017 PloS one Table HIV V118I 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V179D 2017 PloS one Table HIV V179D 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V179T 2017 PloS one Table HIV V179T 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V75I 2017 PloS one Table HIV V75I 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. V90I 2017 PloS one Table HIV V90I 0 4 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Y115F 2017 PloS one Table HIV Y115F 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Y181C 2017 PloS one Table HIV Y181C 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Y181L 2017 PloS one Table HIV Y181L 0 5 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Y188C 2017 PloS one Table HIV Y188C 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. A374G 2017 Scientific reports Table HIV A374G 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. A374N 2017 Scientific reports Table HIV A374N 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. A374S 2017 Scientific reports Table HIV A374S 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. A374T 2017 Scientific reports Table HIV A374T 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. D67N 2017 Scientific reports Table HIV D67N 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. E138Q 2017 Scientific reports Table HIV E138Q 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. E35G 2017 Scientific reports Table HIV E35G 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. G381S 2017 Scientific reports Table HIV G381S 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. H221Y 2017 Scientific reports Table HIV H221Y 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. I376V 2017 Scientific reports Table HIV I376V 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K101E 2017 Scientific reports Table HIV K101E 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K103N 2017 Scientific reports Table HIV K103N 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K20I 2017 Scientific reports Table HIV K20I 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K20V 2017 Scientific reports Table HIV K20V 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K219E 2017 Scientific reports Table HIV K219E 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K219E/Q 2017 Scientific reports Table HIV K219E;K219Q 0;0 7;7 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K219Q 2017 Scientific reports Table HIV K219Q 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K43T 2017 Scientific reports Table HIV K43T 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K65R 2017 Scientific reports Table HIV K65R 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. K70R 2017 Scientific reports Table HIV K70R 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. L100I 2017 Scientific reports Table HIV L100I 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. L10I 2017 Scientific reports Table HIV L10I 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. L10V 2017 Scientific reports Table HIV L10V 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. L33F 2017 Scientific reports Table HIV L33F 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. M184V 2017 Scientific reports Table HIV M184V 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. P225H 2017 Scientific reports Table HIV P225H 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. R380K 2017 Scientific reports Table HIV R380K 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. S373A 2017 Scientific reports Table HIV S373A 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. S373Q 2017 Scientific reports Table HIV S373Q 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. S373T 2017 Scientific reports Table HIV S373T 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. T215F 2017 Scientific reports Table HIV T215F 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. T375A 2017 Scientific reports Table HIV T375A 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. T375G 2017 Scientific reports Table HIV T375G 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. T375N 2017 Scientific reports Table HIV T375N 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. T375S 2017 Scientific reports Table HIV T375S 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. T69D 2017 Scientific reports Table HIV T69D 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. T69N 2017 Scientific reports Table HIV T69N 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. V106A 2017 Scientific reports Table HIV V106A 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. V106M 2017 Scientific reports Table HIV V106M 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. V106M/A 2017 Scientific reports Table HIV V106A;V106M 0;0 7;7 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. V108I 2017 Scientific reports Table HIV V108I 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. V11I 2017 Scientific reports Table HIV V11I 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. V82L 2017 Scientific reports Table HIV V82L 0 4 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Y115F 2017 Scientific reports Table HIV Y115F 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Y181C 2017 Scientific reports Table HIV Y181C 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Y188L 2017 Scientific reports Table HIV Y188L 0 5 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. L33F 2015 Biochemistry and biophysics reports Table HIV L33F 0 4 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. A128T 2017 Virology journal Table HIV A128T 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. E138D 2017 Virology journal Table HIV E138D 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. E157Q 2017 Virology journal Table HIV E157Q 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. G163E 2017 Virology journal Table HIV G163E 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. G163R 2017 Virology journal Table HIV G163R 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. G193E 2017 Virology journal Table HIV G193E 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. G59E 2017 Virology journal Table HIV G59E 0 4 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. H171Q 2017 Virology journal Table HIV H171Q 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. I203M 2017 Virology journal Table HIV I203M 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. L101I 2017 Virology journal Table HIV L101I 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. L68V 2017 Virology journal Table HIV L68V 0 4 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. L74I 2017 Virology journal Table HIV L74I 0 4 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. M154I 2017 Virology journal Table HIV M154I 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. M50I 2017 Virology journal Table HIV M50I 0 4 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. S119R 2017 Virology journal Table HIV S119R 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. S230G 2017 Virology journal Table HIV S230G 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. T122I 2017 Virology journal Table HIV T122I 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. T124A 2017 Virology journal Table HIV T124A 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. T125A 2017 Virology journal Table HIV T125A 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. T206S 2017 Virology journal Table HIV T206S 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. V151A 2017 Virology journal Table HIV V151A 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. V151I 2017 Virology journal Table HIV V151I 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. V165I 2017 Virology journal Table HIV V165I 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. V201I 2017 Virology journal Table HIV V201I 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. V260I 2017 Virology journal Table HIV V260I 0 5 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. V54I 2017 Virology journal Table HIV V54I 0 4 29176596 Quenching protein dynamics interferes with HIV capsid maturation. A92E 2017 Nature communications Table HIV A92E 0 4 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. A316W 2018 The Journal of biological chemistry Table HIV A316W 0 5 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. R308L 2018 The Journal of biological chemistry Table HIV R308L 0 5 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. S306L 2018 The Journal of biological chemistry Table HIV S306L 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. D67N 2017 PloS one Table HIV D67N 0 4 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. G190A 2017 PloS one Table HIV G190A 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. K101E 2017 PloS one Table HIV K101E 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. K101P 2017 PloS one Table HIV K101P 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. K103N 2017 PloS one Table HIV K103N 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. K65R 2017 PloS one Table HIV K65R 0 4 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. K70E 2017 PloS one Table HIV K70E 0 4 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. K70R 2017 PloS one Table HIV K70R 0 4 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. L90M 2017 PloS one Table HIV L90M 0 4 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. M184V 2017 PloS one Table HIV M184V 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. M41L 2017 PloS one Table HIV M41L 0 4 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. P225H 2017 PloS one Table HIV P225H 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. T215F 2017 PloS one Table HIV T215F 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. V106M 2017 PloS one Table HIV V106M 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. V179D 2017 PloS one Table HIV V179D 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. Y181C 2017 PloS one Table HIV Y181C 0 5 29244809 HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study. Y188L 2017 PloS one Table HIV Y188L 0 5 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. G190A 2018 PloS one Table HIV G190A 0 5 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. K65R 2018 Scientific reports Table HIV K65R 0 4 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. V75I 2018 Scientific reports Table HIV V75I 0 4 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. F116Y 2018 Scientific reports Table HIV F116Y 0 5 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. F160L 2018 Scientific reports Table HIV F160L 0 5 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. G112S 2018 Scientific reports Table HIV G112S 0 5 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. L74V 2018 Scientific reports Table HIV L74V 0 4 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Q151M 2018 Scientific reports Table HIV Q151M 0 5 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Y115F 2018 Scientific reports Table HIV Y115F 0 5 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. G73D 2018 Journal of clinical virology Table HIV G73D 0 4 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. I50I/L 2018 Journal of clinical virology Table HIV I50I;I50L 0;0 6;6 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. I50L 2018 Journal of clinical virology Table HIV I50L 0 4 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. I54T 2018 Journal of clinical virology Table HIV I54T 0 4 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. K20K 2018 Journal of clinical virology Table HIV K20K 0 4 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. K20T 2018 Journal of clinical virology Table HIV K20T 0 4 29428459 Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy. L89V 2018 Journal of clinical virology Table HIV L89V 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. A71V 2018 mBio Table HIV A71V 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. I15V 2018 mBio Table HIV I15V 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. I54M 2018 mBio Table HIV I54M 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. I84V 2018 mBio Table HIV I84V 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. K20R 2018 mBio Table HIV K20R 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. K70Q 2018 mBio Table HIV K70Q 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. L10I 2018 mBio Table HIV L10I 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. L24I 2018 mBio Table HIV L24I 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. L33F 2018 mBio Table HIV L33F 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. L63P 2018 mBio Table HIV L63P 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. M36I 2018 mBio Table HIV M36I 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. M46L 2018 mBio Table HIV M46L 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. V32I 2018 mBio Table HIV V32I 0 4 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. V82I 2018 mBio Table HIV V82I 0 4 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. E138A 2018 Antiviral chemistry & chemotherapy Table HIV E138A 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. E138K 2018 Antiviral chemistry & chemotherapy Table HIV E138K 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. F227C 2018 Antiviral chemistry & chemotherapy Table HIV F227C 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. G190A 2018 Antiviral chemistry & chemotherapy Table HIV G190A 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. H221Y 2018 Antiviral chemistry & chemotherapy Table HIV H221Y 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. K101E 2018 Antiviral chemistry & chemotherapy Table HIV K101E 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. K103N 2018 Antiviral chemistry & chemotherapy Table HIV K103N 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. L100I 2018 Antiviral chemistry & chemotherapy Table HIV L100I 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. M230L 2018 Antiviral chemistry & chemotherapy Table HIV M230L 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. P225H 2018 Antiviral chemistry & chemotherapy Table HIV P225H 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. V106M 2018 Antiviral chemistry & chemotherapy Table HIV V106M 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. V108I 2018 Antiviral chemistry & chemotherapy Table HIV V108I 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. V179I 2018 Antiviral chemistry & chemotherapy Table HIV V179I 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. V179L 2018 Antiviral chemistry & chemotherapy Table HIV V179L 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Y181C 2018 Antiviral chemistry & chemotherapy Table HIV Y181C 0 5 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Y188L 2018 Antiviral chemistry & chemotherapy Table HIV Y188L 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. D30N 2018 PLoS medicine Table HIV D30N 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. D67N 2018 PLoS medicine Table HIV D67N 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. G190A 2018 PLoS medicine Table HIV G190A 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. G73S 2018 PLoS medicine Table HIV G73S 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. K101E 2018 PLoS medicine Table HIV K101E 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. K103N 2018 PLoS medicine Table HIV K103N 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. K219Q 2018 PLoS medicine Table HIV K219Q 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. K70R 2018 PLoS medicine Table HIV K70R 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. L74V 2018 PLoS medicine Table HIV L74V 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. M184I 2018 PLoS medicine Table HIV M184I 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. M184V 2018 PLoS medicine Table HIV M184V 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. M41L 2018 PLoS medicine Table HIV M41L 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. N88D 2018 PLoS medicine Table HIV N88D 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. T215A 2018 PLoS medicine Table HIV T215A 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. T215C 2018 PLoS medicine Table HIV T215C 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. T215D 2018 PLoS medicine Table HIV T215D 0 5 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. V82T 2018 PLoS medicine Table HIV V82T 0 4 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. Y181C 2018 PLoS medicine Table HIV Y181C 0 5 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. E297R 2018 mBio Table HIV E297R 0 5 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. E298R 2018 mBio Table HIV E298R 0 5 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. E300R 2018 mBio Table HIV E300R 0 5 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. A62V 2018 AIDS research and therapy Table HIV A62V 0 4 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. D67N 2018 AIDS research and therapy Table HIV D67N 0 4 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. F116Y 2018 AIDS research and therapy Table HIV F116Y 0 5 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. F77L 2018 AIDS research and therapy Table HIV F77L 0 4 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. K219Q/E 2018 AIDS research and therapy Table HIV K219E;K219Q 0;0 7;7 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. K65R 2018 AIDS research and therapy Table HIV K65R 0 4 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. K70R 2018 AIDS research and therapy Table HIV K70R 0 4 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. L210W 2018 AIDS research and therapy Table HIV L210W 0 5 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Q151M 2018 AIDS research and therapy Table HIV Q151M 0 5 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. T215Y/F 2018 AIDS research and therapy Table HIV T215F;T215Y 0;0 7;7 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. V75I 2018 AIDS research and therapy Table HIV V75I 0 4 29684083 HIV-1 transmission networks across Cyprus (2010-2012). K103N 2018 PloS one Table HIV K103N 0 5 29684083 HIV-1 transmission networks across Cyprus (2010-2012). M46L 2018 PloS one Table HIV M46L 0 4 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. K103N 2018 PloS one Table HIV K103N 0 5 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. T215D 2018 PloS one Table HIV T215D 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. A62V 2018 African journal of laboratory medicine Table HIV A62V 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. A98G 2018 African journal of laboratory medicine Table HIV A98G 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. D30N 2018 African journal of laboratory medicine Table HIV D30N 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. D67N 2018 African journal of laboratory medicine Table HIV D67N 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. E138A 2018 African journal of laboratory medicine Table HIV E138A 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. E138K 2018 African journal of laboratory medicine Table HIV E138K 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. E44D 2018 African journal of laboratory medicine Table HIV E44D 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. G190A 2018 African journal of laboratory medicine Table HIV G190A 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. G190E 2018 African journal of laboratory medicine Table HIV G190E 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. G190R 2018 African journal of laboratory medicine Table HIV G190R 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. H221Y 2018 African journal of laboratory medicine Table HIV H221Y 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K101E 2018 African journal of laboratory medicine Table HIV K101E 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K101P 2018 African journal of laboratory medicine Table HIV K101P 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K103N 2018 African journal of laboratory medicine Table HIV K103N 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K138T 2018 African journal of laboratory medicine Table HIV K138T 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K219E 2018 African journal of laboratory medicine Table HIV K219E 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K65R 2018 African journal of laboratory medicine Table HIV K65R 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K70R 2018 African journal of laboratory medicine Table HIV K70R 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. M184I 2018 African journal of laboratory medicine Table HIV M184I 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. M184V 2018 African journal of laboratory medicine Table HIV M184V 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. M41L 2018 African journal of laboratory medicine Table HIV M41L 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. M46I 2018 African journal of laboratory medicine Table HIV M46I 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. M46L 2018 African journal of laboratory medicine Table HIV M46L 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. T215F 2018 African journal of laboratory medicine Table HIV T215F 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. T69D 2018 African journal of laboratory medicine Table HIV T69D 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. T69N 2018 African journal of laboratory medicine Table HIV T69N 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V106A 2018 African journal of laboratory medicine Table HIV V106A 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V106M 2018 African journal of laboratory medicine Table HIV V106M 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V108I 2018 African journal of laboratory medicine Table HIV V108I 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V118I 2018 African journal of laboratory medicine Table HIV V118I 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V179D 2018 African journal of laboratory medicine Table HIV V179D 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V179E 2018 African journal of laboratory medicine Table HIV V179E 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V179T 2018 African journal of laboratory medicine Table HIV V179T 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V75I 2018 African journal of laboratory medicine Table HIV V75I 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V75M 2018 African journal of laboratory medicine Table HIV V75M 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. V90I 2018 African journal of laboratory medicine Table HIV V90I 0 4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Y106M 2018 African journal of laboratory medicine Table HIV Y106M 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Y108I 2018 African journal of laboratory medicine Table HIV Y108I 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Y181C 2018 African journal of laboratory medicine Table HIV Y181C 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Y181I 2018 African journal of laboratory medicine Table HIV Y181I 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Y188C 2018 African journal of laboratory medicine Table HIV Y188C 0 5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Y188L 2018 African journal of laboratory medicine Table HIV Y188L 0 5 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. M184V 2018 Open forum infectious diseases Table HIV M184V 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. D67N 2018 The Pan African medical journal Table HIV D67N 0 4 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. G190A 2018 The Pan African medical journal Table HIV G190A 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. K101N 2018 The Pan African medical journal Table HIV K101N 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. K103N 2018 The Pan African medical journal Table HIV K103N 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. K219Q 2018 The Pan African medical journal Table HIV K219Q 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. K219R 2018 The Pan African medical journal Table HIV K219R 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. K70L 2018 The Pan African medical journal Table HIV K70L 0 4 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. K70R 2018 The Pan African medical journal Table HIV K70R 0 4 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. L210W 2018 The Pan African medical journal Table HIV L210W 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. M184V 2018 The Pan African medical journal Table HIV M184V 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. M41L 2018 The Pan African medical journal Table HIV M41L 0 4 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. T215F 2018 The Pan African medical journal Table HIV T215F 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. T215P 2018 The Pan African medical journal Table HIV T215P 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. T215S 2018 The Pan African medical journal Table HIV T215S 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. T69N 2018 The Pan African medical journal Table HIV T69N 0 4 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. V75A 2018 The Pan African medical journal Table HIV V75A 0 4 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. V75I 2018 The Pan African medical journal Table HIV V75I 0 4 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. Y181C 2018 The Pan African medical journal Table HIV Y181C 0 5 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. Y188L 2018 The Pan African medical journal Table HIV Y188L 0 5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. I559P 2018 Frontiers in immunology Table HIV I559P 0 5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. L553P 2018 Frontiers in immunology Table HIV L553P 0 5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. L555P 2018 Frontiers in immunology Table HIV L555P 0 5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. N554P 2018 Frontiers in immunology Table HIV N554P 0 5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Q562P 2018 Frontiers in immunology Table HIV Q562P 0 5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Q563P 2018 Frontiers in immunology Table HIV Q563P 0 5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. S553P 2018 Frontiers in immunology Table HIV S553P 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A124AT 2018 Retrovirology Table HIV A124A;A124T 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A124N 2018 Retrovirology Table HIV A124N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A124T 2018 Retrovirology Table HIV A124T 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A128AT 2018 Retrovirology Table HIV A128A;A128T 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A128T 2018 Retrovirology Table HIV A128T 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A21T 2018 Retrovirology Table HIV A21T 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A23V 2018 Retrovirology Table HIV A23V 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A265AV 2018 Retrovirology Table HIV A265A;A265V 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D10E 2018 Retrovirology Table HIV D10E 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D167E 2018 Retrovirology Table HIV D167E 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D207N 2018 Retrovirology Table HIV D207N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D232N 2018 Retrovirology Table HIV D232N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D256E 2018 Retrovirology Table HIV D256E 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D25E 2018 Retrovirology Table HIV D25E 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D278A 2018 Retrovirology Table HIV D278A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D286N 2018 Retrovirology Table HIV D286N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. D288N 2018 Retrovirology Table HIV D288N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. E11D 2018 Retrovirology Table HIV E11D 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. E138A 2018 Retrovirology Table HIV E138A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. E138EK 2018 Retrovirology Table HIV E138E;E138K 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. E138K 2018 Retrovirology Table HIV E138K 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. E157Q 2018 Retrovirology Table HIV E157Q 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. E92Q 2018 Retrovirology Table HIV E92Q 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. E92V 2018 Retrovirology Table HIV E92V 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. F100Y 2018 Retrovirology Table HIV F100Y 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. F121Y 2018 Retrovirology Table HIV F121Y 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. F181L 2018 Retrovirology Table HIV F181L 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G106A 2018 Retrovirology Table HIV G106A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G123CS 2018 Retrovirology Table HIV G123C;G123S 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G123S 2018 Retrovirology Table HIV G123S 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G134DG 2018 Retrovirology Table HIV G134D;G134G 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G134N 2018 Retrovirology Table HIV G134N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G140A 2018 Retrovirology Table HIV G140A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G140GS 2018 Retrovirology Table HIV G140G;G140S 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G140S 2018 Retrovirology Table HIV G140S 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G163R 2018 Retrovirology Table HIV G163R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. G193E 2018 Retrovirology Table HIV G193E 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. H51Y 2018 Retrovirology Table HIV H51Y 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I113V 2018 Retrovirology Table HIV I113V 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I135V 2018 Retrovirology Table HIV I135V 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I162IV 2018 Retrovirology Table HIV I162I;I162V 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I203M 2018 Retrovirology Table HIV I203M 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I208IL 2018 Retrovirology Table HIV I208I;I208L 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I220L 2018 Retrovirology Table HIV I220L 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I220V 2018 Retrovirology Table HIV I220V 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. I84M 2018 Retrovirology Table HIV I84M 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K111A 2018 Retrovirology Table HIV K111A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K111E 2018 Retrovirology Table HIV K111E 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K111Q 2018 Retrovirology Table HIV K111Q 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K111R 2018 Retrovirology Table HIV K111R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K136Q 2018 Retrovirology Table HIV K136Q 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K136R 2018 Retrovirology Table HIV K136R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K136T 2018 Retrovirology Table HIV K136T 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K14R 2018 Retrovirology Table HIV K14R 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K156N 2018 Retrovirology Table HIV K156N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K160E 2018 Retrovirology Table HIV K160E 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K160Q 2018 Retrovirology Table HIV K160Q 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K211R 2018 Retrovirology Table HIV K211R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. K215N 2018 Retrovirology Table HIV K215N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L101I 2018 Retrovirology Table HIV L101I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L234I 2018 Retrovirology Table HIV L234I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L234V 2018 Retrovirology Table HIV L234V 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L28I 2018 Retrovirology Table HIV L28I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L45I 2018 Retrovirology Table HIV L45I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L45Q 2018 Retrovirology Table HIV L45Q 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L45V 2018 Retrovirology Table HIV L45V 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L74I 2018 Retrovirology Table HIV L74I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. L74M 2018 Retrovirology Table HIV L74M 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. M154I 2018 Retrovirology Table HIV M154I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. M50I 2018 Retrovirology Table HIV M50I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. M50L 2018 Retrovirology Table HIV M50L 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. N155H 2018 Retrovirology Table HIV N155H 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. N232D 2018 Retrovirology Table HIV N232D 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. P90S 2018 Retrovirology Table HIV P90S 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q146I 2018 Retrovirology Table HIV Q146I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q146R 2018 Retrovirology Table HIV Q146R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q147G 2018 Retrovirology Table HIV Q147G 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q148K 2018 Retrovirology Table HIV Q148K 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q148R 2018 Retrovirology Table HIV Q148R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q95K 2018 Retrovirology Table HIV Q95K 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q95P 2018 Retrovirology Table HIV Q95P 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Q95R 2018 Retrovirology Table HIV Q95R 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. R127K 2018 Retrovirology Table HIV R127K 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. R20K 2018 Retrovirology Table HIV R20K 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. R263K 2018 Retrovirology Table HIV R263K 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. R269K 2018 Retrovirology Table HIV R269K 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. R284G 2018 Retrovirology Table HIV R284G 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. R284GR 2018 Retrovirology Table HIV R284G;R284R 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S119G 2018 Retrovirology Table HIV S119G 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S119P 2018 Retrovirology Table HIV S119P 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S119PRST 2018 Retrovirology Table HIV S119P;S119R;S119S;S119T 0;0;0;0 8;8;8;8 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S119R 2018 Retrovirology Table HIV S119R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S119RS 2018 Retrovirology Table HIV S119R;S119S 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S119T 2018 Retrovirology Table HIV S119T 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S147G 2018 Retrovirology Table HIV S147G 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S153A 2018 Retrovirology Table HIV S153A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S153F 2018 Retrovirology Table HIV S153F 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S153Y 2018 Retrovirology Table HIV S153Y 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S153Y/F 2018 Retrovirology Table HIV S153F;S153Y 0;0 7;7 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S17N 2018 Retrovirology Table HIV S17N 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S195T 2018 Retrovirology Table HIV S195T 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S230N 2018 Retrovirology Table HIV S230N 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S230R 2018 Retrovirology Table HIV S230R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S24N 2018 Retrovirology Table HIV S24N 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S263K 2018 Retrovirology Table HIV S263K 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S283G 2018 Retrovirology Table HIV S283G 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S283GS 2018 Retrovirology Table HIV S283G;S283S 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S39C 2018 Retrovirology Table HIV S39C 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. S39N 2018 Retrovirology Table HIV S39N 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T112A 2018 Retrovirology Table HIV T112A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T112IT 2018 Retrovirology Table HIV T112I;T112T 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T112IV 2018 Retrovirology Table HIV T112I;T112V 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T112V 2018 Retrovirology Table HIV T112V 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T122IT 2018 Retrovirology Table HIV T122I;T122T 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T125A 2018 Retrovirology Table HIV T125A 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T125V 2018 Retrovirology Table HIV T125V 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T206S 2018 Retrovirology Table HIV T206S 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T218I 2018 Retrovirology Table HIV T218I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T218L 2018 Retrovirology Table HIV T218L 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T218S 2018 Retrovirology Table HIV T218S 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T66I 2018 Retrovirology Table HIV T66I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T66K 2018 Retrovirology Table HIV T66K 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T93S 2018 Retrovirology Table HIV T93S 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. T97A 2018 Retrovirology Table HIV T97A 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V151I 2018 Retrovirology Table HIV V151I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V201I 2018 Retrovirology Table HIV V201I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V201IV 2018 Retrovirology Table HIV V201I;V201V 0;0 6;6 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V249I 2018 Retrovirology Table HIV V249I 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V31I 2018 Retrovirology Table HIV V31I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V32I 2018 Retrovirology Table HIV V32I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V37I 2018 Retrovirology Table HIV V37I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V72I 2018 Retrovirology Table HIV V72I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. V79I 2018 Retrovirology Table HIV V79I 0 4 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Y143R 2018 Retrovirology Table HIV Y143R 0 5 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Y227F 2018 Retrovirology Table HIV Y227F 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. A98G 2018 Virology journal Table HIV A98G 0 4 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. D67G 2018 Virology journal Table HIV D67G 0 4 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. E138A 2018 Virology journal Table HIV E138A 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. K219E 2018 Virology journal Table HIV K219E 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. K70R 2018 Virology journal Table HIV K70R 0 4 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. T215I 2018 Virology journal Table HIV T215I 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. T215S 2018 Virology journal Table HIV T215S 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. T215Y 2018 Virology journal Table HIV T215Y 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. V106A 2018 Virology journal Table HIV V106A 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. V75S 2018 Virology journal Table HIV V75S 0 4 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Y115F 2018 Virology journal Table HIV Y115F 0 5 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Y181C 2018 Virology journal Table HIV Y181C 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. A62V 2018 PloS one Table HIV A62V 0 4 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. E138A 2018 PloS one Table HIV E138A 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. E138G 2018 PloS one Table HIV E138G 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. G190A 2018 PloS one Table HIV G190A 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. G190E 2018 PloS one Table HIV G190E 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. G73S 2018 PloS one Table HIV G73S 0 4 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. M184I 2018 PloS one Table HIV M184I 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. M230I 2018 PloS one Table HIV M230I 0 5 30286160 HIV-1C proviral DNA for detection of drug resistance mutations. M46I 2018 PloS one Table HIV M46I 0 4 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. D67E 2018 PloS one Table HIV D67E 0 4 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. F53L 2018 PloS one Table HIV F53L 0 4 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. G190A 2018 PloS one Table HIV G190A 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. G190E 2018 PloS one Table HIV G190E 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. G190S 2018 PloS one Table HIV G190S 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. I85V 2018 PloS one Table HIV I85V 0 4 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. K101E 2018 PloS one Table HIV K101E 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. K103N 2018 PloS one Table HIV K103N 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. L210W 2018 PloS one Table HIV L210W 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. M184I 2018 PloS one Table HIV M184I 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. M46I 2018 PloS one Table HIV M46I 0 4 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. Y181C 2018 PloS one Table HIV Y181C 0 5 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. Y181I 2018 PloS one Table HIV Y181I 0 5 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. G190S 2018 PloS one Table HIV G190S 0 5 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. K101E 2018 PloS one Table HIV K101E 0 5 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. K103N 2018 PloS one Table HIV K103N 0 5 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. K103N/S 2018 PloS one Table HIV K103N;K103S 0;0 7;7 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. M184V 2018 PloS one Table HIV M184V 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. E138A 2018 PloS one Table HIV E138A 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. K103N 2018 PloS one Table HIV K103N 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. K219Q 2018 PloS one Table HIV K219Q 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. L90M 2018 PloS one Table HIV L90M 0 4 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. M184V 2018 PloS one Table HIV M184V 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. M41L 2018 PloS one Table HIV M41L 0 4 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. M46I 2018 PloS one Table HIV M46I 0 4 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. M46I/L 2018 PloS one Table HIV M46I;M46L 0;0 6;6 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. M46L 2018 PloS one Table HIV M46L 0 4 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Q58E 2018 PloS one Table HIV Q58E 0 4 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. T215E 2018 PloS one Table HIV T215E 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. T215S 2018 PloS one Table HIV T215S 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. V108I 2018 PloS one Table HIV V108I 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. V82L 2018 PloS one Table HIV V82L 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. D67E 2018 BMC infectious diseases Table HIV D67E 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. D67N 2018 BMC infectious diseases Table HIV D67N 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. E44D 2018 BMC infectious diseases Table HIV E44D 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. F227Y 2018 BMC infectious diseases Table HIV F227Y 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. G190A 2018 BMC infectious diseases Table HIV G190A 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. G190S 2018 BMC infectious diseases Table HIV G190S 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. H221Y 2018 BMC infectious diseases Table HIV H221Y 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K101E 2018 BMC infectious diseases Table HIV K101E 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K101H 2018 BMC infectious diseases Table HIV K101H 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K103S 2018 BMC infectious diseases Table HIV K103S 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K219E 2018 BMC infectious diseases Table HIV K219E 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K219Q 2018 BMC infectious diseases Table HIV K219Q 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K238H 2018 BMC infectious diseases Table HIV K238H 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K70Q 2018 BMC infectious diseases Table HIV K70Q 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. K70R 2018 BMC infectious diseases Table HIV K70R 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. M184I 2018 BMC infectious diseases Table HIV M184I 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. P225H 2018 BMC infectious diseases Table HIV P225H 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. T215D 2018 BMC infectious diseases Table HIV T215D 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. T215F 2018 BMC infectious diseases Table HIV T215F 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. T215Y 2018 BMC infectious diseases Table HIV T215Y 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. T69D 2018 BMC infectious diseases Table HIV T69D 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. T69P 2018 BMC infectious diseases Table HIV T69P 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. V106A 2018 BMC infectious diseases Table HIV V106A 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. V106I 2018 BMC infectious diseases Table HIV V106I 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. V108I 2018 BMC infectious diseases Table HIV V108I 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. V118I 2018 BMC infectious diseases Table HIV V118I 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. V75I 2018 BMC infectious diseases Table HIV V75I 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. V90I 2018 BMC infectious diseases Table HIV V90I 0 4 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. Y181C 2018 BMC infectious diseases Table HIV Y181C 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. Y188C 2018 BMC infectious diseases Table HIV Y188C 0 5 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. Y188L 2018 BMC infectious diseases Table HIV Y188L 0 5 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. D67N 2019 The Journal of antimicrobial chemotherapy Table HIV D67N 0 4 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. K219E 2019 The Journal of antimicrobial chemotherapy Table HIV K219E 0 5 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. K219Q/E 2019 The Journal of antimicrobial chemotherapy Table HIV K219E;K219Q 0;0 7;7 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. K70R 2019 The Journal of antimicrobial chemotherapy Table HIV K70R 0 4 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. L210W 2019 The Journal of antimicrobial chemotherapy Table HIV L210W 0 5 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. M41L 2019 The Journal of antimicrobial chemotherapy Table HIV M41L 0 4 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. T215F 2019 The Journal of antimicrobial chemotherapy Table HIV T215F 0 5 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. T215Y 2019 The Journal of antimicrobial chemotherapy Table HIV T215Y 0 5 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. D67N 2018 PloS one Table HIV D67N 0 4 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. K101E 2018 PloS one Table HIV K101E 0 5 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. K103N 2018 PloS one Table HIV K103N 0 5 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. M184V 2018 PloS one Table HIV M184V 0 5 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. Y181C 2018 PloS one Table HIV Y181C 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. D30N 2019 Open forum infectious diseases Table HIV D30N 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. D67N 2019 Open forum infectious diseases Table HIV D67N 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. H221Y 2019 Open forum infectious diseases Table HIV H221Y 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. K20T 2019 Open forum infectious diseases Table HIV K20T 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. K219Q 2019 Open forum infectious diseases Table HIV K219Q 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. K43T 2019 Open forum infectious diseases Table HIV K43T 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. L10I 2019 Open forum infectious diseases Table HIV L10I 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. L33F 2019 Open forum infectious diseases Table HIV L33F 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. M184V 2019 Open forum infectious diseases Table HIV M184V 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. N88D 2019 Open forum infectious diseases Table HIV N88D 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. R263K 2019 Open forum infectious diseases Table HIV R263K 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. T215S 2019 Open forum infectious diseases Table HIV T215S 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. T69D 2019 Open forum infectious diseases Table HIV T69D 0 4 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. Y181C 2019 Open forum infectious diseases Table HIV Y181C 0 5 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. Y188L 2019 Open forum infectious diseases Table HIV Y188L 0 5 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. K169E 2019 Journal of virology Table HIV K169E 0 5 30788976 Synthesis and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors. K103N 2019 Antiviral chemistry & chemotherapy Table HIV K103N 0 5 30788976 Synthesis and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors. Y181C 2019 Antiviral chemistry & chemotherapy Table HIV Y181C 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. A583T 2019 mBio Table HIV A583T 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. C17T 2019 mBio Table HIV C17T 0 4 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. C206stop 2019 mBio Table HIV C206X 0 8 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. C9007A 2019 mBio Table HIV C9007A 0 6 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. E12K 2019 mBio Table HIV E12K 0 4 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. E40K 2019 mBio Table HIV E40K 0 4 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. E434K 2019 mBio Table HIV E434K 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. E59K 2019 mBio Table HIV E59K 0 4 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. I223T 2019 mBio Table HIV I223T 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. I520M 2019 mBio Table HIV I520M 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. K660E 2019 mBio Table HIV K660E 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. L491V 2019 mBio Table HIV L491V 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. N306K 2019 mBio Table HIV N306K 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Q555H 2019 mBio Table HIV Q555H 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. R361K 2019 mBio Table HIV R361K 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. R538A 2019 mBio Table HIV R538A 0 5 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. V142I 2019 mBio Table HIV V142I 0 5 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. H547A 2019 Scientific reports Table HIV H547A 0 5 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. K92M 2019 Scientific reports Table HIV K92M 0 4 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Y88A 2019 Scientific reports Table HIV Y88A 0 4 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Y88F 2019 Scientific reports Table HIV Y88F 0 4 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. K103N 2019 Open forum infectious diseases Table HIV K103N 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. F122I 2019 PeerJ Table HIV F122I 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. F122L 2019 PeerJ Table HIV F122L 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. L109R 2019 PeerJ Table HIV L109R 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. L145M 2019 PeerJ Table HIV L145M 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. L199V 2019 PeerJ Table HIV L199V 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. L217F 2019 PeerJ Table HIV L217F 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. L91I 2019 PeerJ Table HIV L91I 0 4 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. M129L 2019 PeerJ Table HIV M129L 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. M133L 2019 PeerJ Table HIV M133L 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. N118D 2019 PeerJ Table HIV N118D 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. Q215H 2019 PeerJ Table HIV Q215H 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. Q215L 2019 PeerJ Table HIV Q215L 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. R110G 2019 PeerJ Table HIV R110G 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. R122K 2019 PeerJ Table HIV R122K 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. S109P 2019 PeerJ Table HIV S109P 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. S117N 2019 PeerJ Table HIV S117N 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. S119P 2019 PeerJ Table HIV S119P 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. S137T 2019 PeerJ Table HIV S137T 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. S143L 2019 PeerJ Table HIV S143L 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. S176T 2019 PeerJ Table HIV S176T 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. S185I 2019 PeerJ Table HIV S185I 0 5 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. Y135S 2019 PeerJ Table HIV Y135S 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. A360V 2019 Journal of virology Table HIV A360V 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. D250V 2019 Journal of virology Table HIV D250V 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. E297G 2019 Journal of virology Table HIV E297G 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. E53G 2019 Journal of virology Table HIV E53G 0 4 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D 2019 Journal of virology Table HIV G112D 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G196R 2019 Journal of virology Table HIV G196R 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. K101E 2019 Journal of virology Table HIV K101E 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. K126E 2019 Journal of virology Table HIV K126E 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. K331E 2019 Journal of virology Table HIV K331E 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. K43R 2019 Journal of virology Table HIV K43R 0 4 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. L391P 2019 Journal of virology Table HIV L391P 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I 2019 Journal of virology Table HIV M230I 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. P433L 2019 Journal of virology Table HIV P433L 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. P55L 2019 Journal of virology Table HIV P55L 0 4 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. R448G 2019 Journal of virology Table HIV R448G 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. S69C 2019 Journal of virology Table HIV S69C 0 4 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. T403I 2019 Journal of virology Table HIV T403I 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. V10I 2019 Journal of virology Table HIV V10I 0 4 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. V381L 2019 Journal of virology Table HIV V381L 0 5 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. A25D 2019 Retrovirology Table HIV A25D 0 4 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. K27D 2019 Retrovirology Table HIV K27D 0 4 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. K30D 2019 Retrovirology Table HIV K30D 0 4 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. P29K 2019 Retrovirology Table HIV P29K 0 4 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. E138K 2019 Acta naturae Table HIV E138K 0 5 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. G118R 2019 Acta naturae Table HIV G118R 0 5 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. G140S 2019 Acta naturae Table HIV G140S 0 5 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Q148K 2019 Acta naturae Table HIV Q148K 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. A128T 2019 Revista espanola de quimioterapia Table HIV A128T 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. E138A 2019 Revista espanola de quimioterapia Table HIV E138A 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. E138A/E 2019 Revista espanola de quimioterapia Table HIV E138A;E138E 0;0 7;7 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. E157Q 2019 Revista espanola de quimioterapia Table HIV E157Q 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. E92A/E 2019 Revista espanola de quimioterapia Table HIV E92A;E92E 0;0 6;6 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. E92Q 2019 Revista espanola de quimioterapia Table HIV E92Q 0 4 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. G140A/S 2019 Revista espanola de quimioterapia Table HIV G140A;G140S 0;0 7;7 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. G163K 2019 Revista espanola de quimioterapia Table HIV G163K 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. G163K/R 2019 Revista espanola de quimioterapia Table HIV G163K;G163R 0;0 7;7 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. G163R 2019 Revista espanola de quimioterapia Table HIV G163R 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. G190A/S 2019 Revista espanola de quimioterapia Table HIV G190A;G190S 0;0 7;7 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. L68V 2019 Revista espanola de quimioterapia Table HIV L68V 0 4 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. L74I 2019 Revista espanola de quimioterapia Table HIV L74I 0 4 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. L74M 2019 Revista espanola de quimioterapia Table HIV L74M 0 4 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. N155H 2019 Revista espanola de quimioterapia Table HIV N155H 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. Q148H/R 2019 Revista espanola de quimioterapia Table HIV Q148H;Q148R 0;0 7;7 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. T66A 2019 Revista espanola de quimioterapia Table HIV T66A 0 4 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. T79A 2019 Revista espanola de quimioterapia Table HIV T79A 0 4 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. T97A 2019 Revista espanola de quimioterapia Table HIV T97A 0 4 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. V151I 2019 Revista espanola de quimioterapia Table HIV V151I 0 5 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. Y143R 2019 Revista espanola de quimioterapia Table HIV Y143R 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. A122A/T 2019 Nature communications Table HIV A122A;A122T 0;0 7;7 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. A122T 2019 Nature communications Table HIV A122T 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. E92E/Q 2019 Nature communications Table HIV E92E;E92Q 0;0 6;6 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. E92G 2019 Nature communications Table HIV E92G 0 4 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. E92Q 2019 Nature communications Table HIV E92Q 0 4 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. G118G/R 2019 Nature communications Table HIV G118G;G118R 0;0 7;7 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. G118R 2019 Nature communications Table HIV G118R 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. G140G/R 2019 Nature communications Table HIV G140G;G140R 0;0 7;7 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. G140R 2019 Nature communications Table HIV G140R 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. I110I/V 2019 Nature communications Table HIV I110I;I110V 0;0 7;7 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. I110V 2019 Nature communications Table HIV I110V 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. I250V 2019 Nature communications Table HIV I250V 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. I72I 2019 Nature communications Table HIV I72I 0 4 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. I72T 2019 Nature communications Table HIV I72T 0 4 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Q124Q/R 2019 Nature communications Table HIV Q124Q;Q124R 0;0 7;7 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Q124R 2019 Nature communications Table HIV Q124R 0 5 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. S123S/A 2019 Nature communications Table HIV S123A;S123S 0;0 7;7 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. A62V 2019 Journal of the International Association of Providers of AIDS Care Table HIV A62V 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. A98G 2019 Journal of the International Association of Providers of AIDS Care Table HIV A98G 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. D67E 2019 Journal of the International Association of Providers of AIDS Care Table HIV D67E 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. D67N 2019 Journal of the International Association of Providers of AIDS Care Table HIV D67N 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. E138K 2019 Journal of the International Association of Providers of AIDS Care Table HIV E138K 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. E44D 2019 Journal of the International Association of Providers of AIDS Care Table HIV E44D 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. F116Y 2019 Journal of the International Association of Providers of AIDS Care Table HIV F116Y 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. F227L 2019 Journal of the International Association of Providers of AIDS Care Table HIV F227L 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. G190A 2019 Journal of the International Association of Providers of AIDS Care Table HIV G190A 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. G190E 2019 Journal of the International Association of Providers of AIDS Care Table HIV G190E 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. G190S 2019 Journal of the International Association of Providers of AIDS Care Table HIV G190S 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. G48M 2019 Journal of the International Association of Providers of AIDS Care Table HIV G48M 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K101E 2019 Journal of the International Association of Providers of AIDS Care Table HIV K101E 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K101Q 2019 Journal of the International Association of Providers of AIDS Care Table HIV K101Q 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K103N 2019 Journal of the International Association of Providers of AIDS Care Table HIV K103N 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K103R 2019 Journal of the International Association of Providers of AIDS Care Table HIV K103R 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K103S 2019 Journal of the International Association of Providers of AIDS Care Table HIV K103S 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K219E 2019 Journal of the International Association of Providers of AIDS Care Table HIV K219E 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K219N 2019 Journal of the International Association of Providers of AIDS Care Table HIV K219N 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K219Q 2019 Journal of the International Association of Providers of AIDS Care Table HIV K219Q 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K238T 2019 Journal of the International Association of Providers of AIDS Care Table HIV K238T 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K65R 2019 Journal of the International Association of Providers of AIDS Care Table HIV K65R 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. K70R 2019 Journal of the International Association of Providers of AIDS Care Table HIV K70R 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. L210W 2019 Journal of the International Association of Providers of AIDS Care Table HIV L210W 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. L74I 2019 Journal of the International Association of Providers of AIDS Care Table HIV L74I 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. L74V 2019 Journal of the International Association of Providers of AIDS Care Table HIV L74V 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. M184V 2019 Journal of the International Association of Providers of AIDS Care Table HIV M184V 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. M41L 2019 Journal of the International Association of Providers of AIDS Care Table HIV M41L 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. M46I 2019 Journal of the International Association of Providers of AIDS Care Table HIV M46I 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Q151M 2019 Journal of the International Association of Providers of AIDS Care Table HIV Q151M 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T215F 2019 Journal of the International Association of Providers of AIDS Care Table HIV T215F 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T215S 2019 Journal of the International Association of Providers of AIDS Care Table HIV T215S 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T215V 2019 Journal of the International Association of Providers of AIDS Care Table HIV T215V 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T215Y 2019 Journal of the International Association of Providers of AIDS Care Table HIV T215Y 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T69D 2019 Journal of the International Association of Providers of AIDS Care Table HIV T69D 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T69ins 2019 Journal of the International Association of Providers of AIDS Care Table HIV T69ins 0 6 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T69N 2019 Journal of the International Association of Providers of AIDS Care Table HIV T69N 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. T74S 2019 Journal of the International Association of Providers of AIDS Care Table HIV T74S 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. V106M 2019 Journal of the International Association of Providers of AIDS Care Table HIV V106M 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. V108I 2019 Journal of the International Association of Providers of AIDS Care Table HIV V108I 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. V118I 2019 Journal of the International Association of Providers of AIDS Care Table HIV V118I 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. V179D 2019 Journal of the International Association of Providers of AIDS Care Table HIV V179D 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. V75A 2019 Journal of the International Association of Providers of AIDS Care Table HIV V75A 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. V75I 2019 Journal of the International Association of Providers of AIDS Care Table HIV V75I 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. V75M 2019 Journal of the International Association of Providers of AIDS Care Table HIV V75M 0 4 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Y115F 2019 Journal of the International Association of Providers of AIDS Care Table HIV Y115F 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Y181C 2019 Journal of the International Association of Providers of AIDS Care Table HIV Y181C 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Y181I 2019 Journal of the International Association of Providers of AIDS Care Table HIV Y181I 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Y181V 2019 Journal of the International Association of Providers of AIDS Care Table HIV Y181V 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Y188C 2019 Journal of the International Association of Providers of AIDS Care Table HIV Y188C 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Y188L 2019 Journal of the International Association of Providers of AIDS Care Table HIV Y188L 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Y318F 2019 Journal of the International Association of Providers of AIDS Care Table HIV Y318F 0 5 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. D25N 2019 ACS omega Table HIV D25N 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. A62V 2019 Infection and drug resistance Table HIV A62V 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. A71V 2019 Infection and drug resistance Table HIV A71V 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. A98G 2019 Infection and drug resistance Table HIV A98G 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. D67N 2019 Infection and drug resistance Table HIV D67N 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. E44D 2019 Infection and drug resistance Table HIV E44D 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. F116Y 2019 Infection and drug resistance Table HIV F116Y 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. F77L 2019 Infection and drug resistance Table HIV F77L 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. G190A 2019 Infection and drug resistance Table HIV G190A 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. G190S 2019 Infection and drug resistance Table HIV G190S 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. H208Y 2019 Infection and drug resistance Table HIV H208Y 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K101E 2019 Infection and drug resistance Table HIV K101E 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K101H 2019 Infection and drug resistance Table HIV K101H 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K101Q 2019 Infection and drug resistance Table HIV K101Q 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K103N 2019 Infection and drug resistance Table HIV K103N 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K20R 2019 Infection and drug resistance Table HIV K20R 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K210R 2019 Infection and drug resistance Table HIV K210R 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K219E 2019 Infection and drug resistance Table HIV K219E 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K219Q 2019 Infection and drug resistance Table HIV K219Q 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K65R 2019 Infection and drug resistance Table HIV K65R 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. K70R 2019 Infection and drug resistance Table HIV K70R 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. L10I 2019 Infection and drug resistance Table HIV L10I 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. L210W 2019 Infection and drug resistance Table HIV L210W 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. L33F 2019 Infection and drug resistance Table HIV L33F 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. L74V 2019 Infection and drug resistance Table HIV L74V 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. M184I/V 2019 Infection and drug resistance Table HIV M184I;M184V 0;0 7;7 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. M184V 2019 Infection and drug resistance Table HIV M184V 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. M230L 2019 Infection and drug resistance Table HIV M230L 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. M36I 2019 Infection and drug resistance Table HIV M36I 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. M41L 2019 Infection and drug resistance Table HIV M41L 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. P225H 2019 Infection and drug resistance Table HIV P225H 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Q151M 2019 Infection and drug resistance Table HIV Q151M 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. T215F 2019 Infection and drug resistance Table HIV T215F 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. T215Y 2019 Infection and drug resistance Table HIV T215Y 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. T69D 2019 Infection and drug resistance Table HIV T69D 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. T69N 2019 Infection and drug resistance Table HIV T69N 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. V106I 2019 Infection and drug resistance Table HIV V106I 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. V108I 2019 Infection and drug resistance Table HIV V108I 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. V118I 2019 Infection and drug resistance Table HIV V118I 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. V179E 2019 Infection and drug resistance Table HIV V179E 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. V179T 2019 Infection and drug resistance Table HIV V179T 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. V75M 2019 Infection and drug resistance Table HIV V75M 0 4 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Y179D 2019 Infection and drug resistance Table HIV Y179D 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Y181C 2019 Infection and drug resistance Table HIV Y181C 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Y181I/C 2019 Infection and drug resistance Table HIV Y181C;Y181I 0;0 7;7 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Y181V 2019 Infection and drug resistance Table HIV Y181V 0 5 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Y188L 2019 Infection and drug resistance Table HIV Y188L 0 5 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. A62V 2019 BMC infectious diseases Table HIV A62V 0 4 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. F116Y 2019 BMC infectious diseases Table HIV F116Y 0 5 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. K65R 2019 BMC infectious diseases Table HIV K65R 0 4 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. K70E 2019 BMC infectious diseases Table HIV K70E 0 4 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. M184I/V 2019 BMC infectious diseases Table HIV M184I;M184V 0;0 7;7 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. V75I 2019 BMC infectious diseases Table HIV V75I 0 4 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. Y115F 2019 BMC infectious diseases Table HIV Y115F 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. D67N 2019 Sexually transmitted infections Table HIV D67N 0 4 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. G190A 2019 Sexually transmitted infections Table HIV G190A 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. K101E 2019 Sexually transmitted infections Table HIV K101E 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. K103N 2019 Sexually transmitted infections Table HIV K103N 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. K219Q 2019 Sexually transmitted infections Table HIV K219Q 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. K65R 2019 Sexually transmitted infections Table HIV K65R 0 4 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. K70R 2019 Sexually transmitted infections Table HIV K70R 0 4 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. L100I 2019 Sexually transmitted infections Table HIV L100I 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. L210W 2019 Sexually transmitted infections Table HIV L210W 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. L74V 2019 Sexually transmitted infections Table HIV L74V 0 4 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. M184V 2019 Sexually transmitted infections Table HIV M184V 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. M41L 2019 Sexually transmitted infections Table HIV M41L 0 4 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. M46L 2019 Sexually transmitted infections Table HIV M46L 0 4 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. P225H 2019 Sexually transmitted infections Table HIV P225H 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. T215Y 2019 Sexually transmitted infections Table HIV T215Y 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. V106M 2019 Sexually transmitted infections Table HIV V106M 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. V179F 2019 Sexually transmitted infections Table HIV V179F 0 5 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. Y181C 2019 Sexually transmitted infections Table HIV Y181C 0 5 31269034 Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study. K65R 2019 PloS one Table HIV K65R 0 4 31269034 Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study. M184V 2019 PloS one Table HIV M184V 0 5 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. E35D 2019 Journal of enzyme inhibition and medicinal chemistry Table HIV E35D 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. A128T 2019 The Journal of antimicrobial chemotherapy Table HIV A128T 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. D30N 2019 The Journal of antimicrobial chemotherapy Table HIV D30N 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. D67N 2019 The Journal of antimicrobial chemotherapy Table HIV D67N 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. E138A/G 2019 The Journal of antimicrobial chemotherapy Table HIV E138A;E138G 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. E138A/K 2019 The Journal of antimicrobial chemotherapy Table HIV E138A;E138K 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. E138E 2019 The Journal of antimicrobial chemotherapy Table HIV E138E 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. E138K 2019 The Journal of antimicrobial chemotherapy Table HIV E138K 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. E157K/Q 2019 The Journal of antimicrobial chemotherapy Table HIV E157K;E157Q 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. E157Q 2019 The Journal of antimicrobial chemotherapy Table HIV E157Q 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. E92G 2019 The Journal of antimicrobial chemotherapy Table HIV E92G 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. F121C 2019 The Journal of antimicrobial chemotherapy Table HIV F121C 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. F227C 2019 The Journal of antimicrobial chemotherapy Table HIV F227C 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. G140S 2019 The Journal of antimicrobial chemotherapy Table HIV G140S 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. G163K/R 2019 The Journal of antimicrobial chemotherapy Table HIV G163K;G163R 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. G190A/E 2019 The Journal of antimicrobial chemotherapy Table HIV G190A;G190E 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. H221Y 2019 The Journal of antimicrobial chemotherapy Table HIV H221Y 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. I47V 2019 The Journal of antimicrobial chemotherapy Table HIV I47V 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. I50V 2019 The Journal of antimicrobial chemotherapy Table HIV I50V 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. I54L 2019 The Journal of antimicrobial chemotherapy Table HIV I54L 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. I84V 2019 The Journal of antimicrobial chemotherapy Table HIV I84V 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K101E/P 2019 The Journal of antimicrobial chemotherapy Table HIV K101E;K101P 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K103N 2019 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K103N/S 2019 The Journal of antimicrobial chemotherapy Table HIV K103N;K103S 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K219E/N 2019 The Journal of antimicrobial chemotherapy Table HIV K219E;K219N 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K219E/Q 2019 The Journal of antimicrobial chemotherapy Table HIV K219E;K219Q 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K65R/N 2019 The Journal of antimicrobial chemotherapy Table HIV K65N;K65R 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K70K/R 2019 The Journal of antimicrobial chemotherapy Table HIV K70K;K70R 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. K70R 2019 The Journal of antimicrobial chemotherapy Table HIV K70R 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L100I 2019 The Journal of antimicrobial chemotherapy Table HIV L100I 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L210W 2019 The Journal of antimicrobial chemotherapy Table HIV L210W 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L68I/V 2019 The Journal of antimicrobial chemotherapy Table HIV L68I;L68V 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L74I/V 2019 The Journal of antimicrobial chemotherapy Table HIV L74I;L74V 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L74L/V 2019 The Journal of antimicrobial chemotherapy Table HIV L74L;L74V 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L74M 2019 The Journal of antimicrobial chemotherapy Table HIV L74M 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L76V 2019 The Journal of antimicrobial chemotherapy Table HIV L76V 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. L90M 2019 The Journal of antimicrobial chemotherapy Table HIV L90M 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M184I 2019 The Journal of antimicrobial chemotherapy Table HIV M184I 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M184M/V 2019 The Journal of antimicrobial chemotherapy Table HIV M184M;M184V 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M184V 2019 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M184V/I 2019 The Journal of antimicrobial chemotherapy Table HIV M184I;M184V 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M230I 2019 The Journal of antimicrobial chemotherapy Table HIV M230I 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M320I/L 2019 The Journal of antimicrobial chemotherapy Table HIV M320I;M320L 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M41L 2019 The Journal of antimicrobial chemotherapy Table HIV M41L 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M46I 2019 The Journal of antimicrobial chemotherapy Table HIV M46I 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M46I/L 2019 The Journal of antimicrobial chemotherapy Table HIV M46I;M46L 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M50I 2019 The Journal of antimicrobial chemotherapy Table HIV M50I 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M50M/I 2019 The Journal of antimicrobial chemotherapy Table HIV M50I;M50M 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. N83D 2019 The Journal of antimicrobial chemotherapy Table HIV N83D 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. N88S 2019 The Journal of antimicrobial chemotherapy Table HIV N88S 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. P225H 2019 The Journal of antimicrobial chemotherapy Table HIV P225H 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Q148H 2019 The Journal of antimicrobial chemotherapy Table HIV Q148H 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Q151M 2019 The Journal of antimicrobial chemotherapy Table HIV Q151M 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Q58E 2019 The Journal of antimicrobial chemotherapy Table HIV Q58E 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. S119P 2019 The Journal of antimicrobial chemotherapy Table HIV S119P 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. S119P/R 2019 The Journal of antimicrobial chemotherapy Table HIV S119P;S119R 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. S119R 2019 The Journal of antimicrobial chemotherapy Table HIV S119R 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. S119S/A 2019 The Journal of antimicrobial chemotherapy Table HIV S119A;S119S 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. S119T 2019 The Journal of antimicrobial chemotherapy Table HIV S119T 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. S147G 2019 The Journal of antimicrobial chemotherapy Table HIV S147G 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. S153A 2019 The Journal of antimicrobial chemotherapy Table HIV S153A 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. T215F/Y 2019 The Journal of antimicrobial chemotherapy Table HIV T215F;T215Y 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. T215Y/F 2019 The Journal of antimicrobial chemotherapy Table HIV T215F;T215Y 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. T97A 2019 The Journal of antimicrobial chemotherapy Table HIV T97A 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V106I 2019 The Journal of antimicrobial chemotherapy Table HIV V106I 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V106V/I 2019 The Journal of antimicrobial chemotherapy Table HIV V106I;V106V 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V108I 2019 The Journal of antimicrobial chemotherapy Table HIV V108I 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V118I 2019 The Journal of antimicrobial chemotherapy Table HIV V118I 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V179L 2019 The Journal of antimicrobial chemotherapy Table HIV V179L 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V32I 2019 The Journal of antimicrobial chemotherapy Table HIV V32I 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V72N 2019 The Journal of antimicrobial chemotherapy Table HIV V72N 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V82A 2019 The Journal of antimicrobial chemotherapy Table HIV V82A 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V82A/L 2019 The Journal of antimicrobial chemotherapy Table HIV V82A;V82L 0;0 6;6 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. V90I 2019 The Journal of antimicrobial chemotherapy Table HIV V90I 0 4 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Y115F 2019 The Journal of antimicrobial chemotherapy Table HIV Y115F 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Y143H 2019 The Journal of antimicrobial chemotherapy Table HIV Y143H 0 5 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Y181C/I 2019 The Journal of antimicrobial chemotherapy Table HIV Y181C;Y181I 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Y188C/H 2019 The Journal of antimicrobial chemotherapy Table HIV Y188C;Y188H 0;0 7;7 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Y188L 2019 The Journal of antimicrobial chemotherapy Table HIV Y188L 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. D30N 2019 PloS one Table HIV D30N 0 4 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. D67N 2019 PloS one Table HIV D67N 0 4 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. F116Y 2019 PloS one Table HIV F116Y 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. F77L 2019 PloS one Table HIV F77L 0 4 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. G190A 2019 PloS one Table HIV G190A 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. K101E 2019 PloS one Table HIV K101E 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. K103N 2019 PloS one Table HIV K103N 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. K219Q 2019 PloS one Table HIV K219Q 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. K70R 2019 PloS one Table HIV K70R 0 4 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. L100I 2019 PloS one Table HIV L100I 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. L210W 2019 PloS one Table HIV L210W 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. L74V 2019 PloS one Table HIV L74V 0 4 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. M184V/I 2019 PloS one Table HIV M184I;M184V 0;0 7;7 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. M230L 2019 PloS one Table HIV M230L 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. M41L 2019 PloS one Table HIV M41L 0 4 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. M46I/L 2019 PloS one Table HIV M46I;M46L 0;0 6;6 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. T215Y 2019 PloS one Table HIV T215Y 0 5 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. V82A 2019 PloS one Table HIV V82A 0 4 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. Y181C 2019 PloS one Table HIV Y181C 0 5 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. G116R 2019 Journal of virology Table HIV G116R 0 5 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. G94D 2019 Journal of virology Table HIV G94D 0 4 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Q112D 2019 Journal of virology Table HIV Q112D 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. A23V 2019 Frontiers in microbiology Table HIV A23V 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. A265V 2019 Frontiers in microbiology Table HIV A265V 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. D232E 2019 Frontiers in microbiology Table HIV D232E 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. D232N 2019 Frontiers in microbiology Table HIV D232N 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. D253E 2019 Frontiers in microbiology Table HIV D253E 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. D256E 2019 Frontiers in microbiology Table HIV D256E 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. D25E 2019 Frontiers in microbiology Table HIV D25E 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. D41N 2019 Frontiers in microbiology Table HIV D41N 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. D6E 2019 Frontiers in microbiology Table HIV D6E 0 3 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. E10D 2019 Frontiers in microbiology Table HIV E10D 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. E11D 2019 Frontiers in microbiology Table HIV E11D 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. E138K 2019 Frontiers in microbiology Table HIV E138K 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. E157Q 2019 Frontiers in microbiology Table HIV E157Q 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. F181L 2019 Frontiers in microbiology Table HIV F181L 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. G140S 2019 Frontiers in microbiology Table HIV G140S 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. G163E 2019 Frontiers in microbiology Table HIV G163E 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. G163R 2019 Frontiers in microbiology Table HIV G163R 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. I135V 2019 Frontiers in microbiology Table HIV I135V 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. I151V 2019 Frontiers in microbiology Table HIV I151V 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. I203M 2019 Frontiers in microbiology Table HIV I203M 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. I208L 2019 Frontiers in microbiology Table HIV I208L 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. K14R 2019 Frontiers in microbiology Table HIV K14R 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. K156N 2019 Frontiers in microbiology Table HIV K156N 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. K160Q 2019 Frontiers in microbiology Table HIV K160Q 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. K211R 2019 Frontiers in microbiology Table HIV K211R 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. K215N 2019 Frontiers in microbiology Table HIV K215N 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. K7R 2019 Frontiers in microbiology Table HIV K7R 0 3 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. L101I 2019 Frontiers in microbiology Table HIV L101I 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. L28I 2019 Frontiers in microbiology Table HIV L28I 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. L45V 2019 Frontiers in microbiology Table HIV L45V 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. L74I 2019 Frontiers in microbiology Table HIV L74I 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. L74M 2019 Frontiers in microbiology Table HIV L74M 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. M154L 2019 Frontiers in microbiology Table HIV M154L 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. M50I 2019 Frontiers in microbiology Table HIV M50I 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. N155H 2019 Frontiers in microbiology Table HIV N155H 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. N222K 2019 Frontiers in microbiology Table HIV N222K 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Q148H 2019 Frontiers in microbiology Table HIV Q148H 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Q148R 2019 Frontiers in microbiology Table HIV Q148R 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Q216H 2019 Frontiers in microbiology Table HIV Q216H 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. R20K 2019 Frontiers in microbiology Table HIV R20K 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. R284G 2019 Frontiers in microbiology Table HIV R284G 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S119G 2019 Frontiers in microbiology Table HIV S119G 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S119P 2019 Frontiers in microbiology Table HIV S119P 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S119R 2019 Frontiers in microbiology Table HIV S119R 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S17N 2019 Frontiers in microbiology Table HIV S17N 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S230N 2019 Frontiers in microbiology Table HIV S230N 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S283G 2019 Frontiers in microbiology Table HIV S283G 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. S39C 2019 Frontiers in microbiology Table HIV S39C 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T112I 2019 Frontiers in microbiology Table HIV T112I 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T122I 2019 Frontiers in microbiology Table HIV T122I 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T124A 2019 Frontiers in microbiology Table HIV T124A 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T124N 2019 Frontiers in microbiology Table HIV T124N 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T125A 2019 Frontiers in microbiology Table HIV T125A 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T125V 2019 Frontiers in microbiology Table HIV T125V 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T206S 2019 Frontiers in microbiology Table HIV T206S 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T218S 2019 Frontiers in microbiology Table HIV T218S 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. T97A 2019 Frontiers in microbiology Table HIV T97A 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V113I 2019 Frontiers in microbiology Table HIV V113I 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V165I 2019 Frontiers in microbiology Table HIV V165I 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V201I 2019 Frontiers in microbiology Table HIV V201I 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V234I 2019 Frontiers in microbiology Table HIV V234I 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V234L 2019 Frontiers in microbiology Table HIV V234L 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V31I 2019 Frontiers in microbiology Table HIV V31I 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V32I 2019 Frontiers in microbiology Table HIV V32I 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V72I 2019 Frontiers in microbiology Table HIV V72I 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. V79I 2019 Frontiers in microbiology Table HIV V79I 0 4 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Y143R 2019 Frontiers in microbiology Table HIV Y143R 0 5 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Y227F 2019 Frontiers in microbiology Table HIV Y227F 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A326A 2019 PloS one Table HIV A326A 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A326S 2019 PloS one Table HIV A326S 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A326T 2019 PloS one Table HIV A326T 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A364A/V 2019 PloS one Table HIV A364A;A364V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A364V 2019 PloS one Table HIV A364V 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A364V/A 2019 PloS one Table HIV A364A;A364V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A366A/V 2019 PloS one Table HIV A366A;A366V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. G221E 2019 PloS one Table HIV G221E 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. H219H/Q 2019 PloS one Table HIV H219H;H219Q 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. H219Q 2019 PloS one Table HIV H219Q 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. I333V 2019 PloS one Table HIV I333V 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. I333V/I 2019 PloS one Table HIV I333I;I333V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. I376V 2019 PloS one Table HIV I376V 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. L363M 2019 PloS one Table HIV L363M 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. P373S 2019 PloS one Table HIV P373S 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Q369Q/H 2019 PloS one Table HIV Q369H;Q369Q 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. R286K 2019 PloS one Table HIV R286K 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. R286K/R 2019 PloS one Table HIV R286K;R286R 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. R286R/K 2019 PloS one Table HIV R286K;R286R 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. T332S 2019 PloS one Table HIV T332S 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. T371N 2019 PloS one Table HIV T371N 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. T371X 2019 PloS one Table HIV T371X 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V362I 2019 PloS one Table HIV V362I 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V362I/V 2019 PloS one Table HIV V362I;V362V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V362V/I 2019 PloS one Table HIV V362I;V362V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V370A 2019 PloS one Table HIV V370A 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V370A/V 2019 PloS one Table HIV V370A;V370V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V370I/V 2019 PloS one Table HIV V370I;V370V 0;0 7;7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V370M 2019 PloS one Table HIV V370M 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. A48T 2019 Retrovirology Table HIV A48T 0 4 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. A612T 2019 Retrovirology Table HIV A612T 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. E83K 2019 Retrovirology Table HIV E83K 0 4 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. F175L 2019 Retrovirology Table HIV F175L 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. G464E 2019 Retrovirology Table HIV G464E 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. H643Y 2019 Retrovirology Table HIV H643Y 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. L663F 2019 Retrovirology Table HIV L663F 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. N136D 2019 Retrovirology Table HIV N136D 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. N136K 2019 Retrovirology Table HIV N136K 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. N301K 2019 Retrovirology Table HIV N301K 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. N460I 2019 Retrovirology Table HIV N460I 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. N674T 2019 Retrovirology Table HIV N674T 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q550H 2019 Retrovirology Table HIV Q550H 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577K 2019 Retrovirology Table HIV Q577K 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577N 2019 Retrovirology Table HIV Q577N 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577R 2019 Retrovirology Table HIV Q577R 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. R146K 2019 Retrovirology Table HIV R146K 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. S306R 2019 Retrovirology Table HIV S306R 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. S465P 2019 Retrovirology Table HIV S465P 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. T19I 2019 Retrovirology Table HIV T19I 0 4 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. T319A 2019 Retrovirology Table HIV T319A 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. V200E 2019 Retrovirology Table HIV V200E 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. V255A 2019 Retrovirology Table HIV V255A 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. V583V 2019 Retrovirology Table HIV V583V 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. V693I 2019 Retrovirology Table HIV V693I 0 5 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. M184V 2019 Open forum infectious diseases Table HIV M184V 0 5 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. M184V/I 2019 Open forum infectious diseases Table HIV M184I;M184V 0;0 7;7 31745412 HIV Drug Resistance among Patients Failing Therapy at a Tertiary Center in Oman: A Case Record Review. M184V 2019 Oman medical journal Table HIV M184V 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. A62V 2019 PloS one Table HIV A62V 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. A90G 2019 PloS one Table HIV A90G 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. A98G 2019 PloS one Table HIV A98G 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. D67N 2019 PloS one Table HIV D67N 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. E138A 2019 PloS one Table HIV E138A 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. E44D 2019 PloS one Table HIV E44D 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. G190A 2019 PloS one Table HIV G190A 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. K101E 2019 PloS one Table HIV K101E 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. K101Q 2019 PloS one Table HIV K101Q 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. K103N 2019 PloS one Table HIV K103N 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. K219E/Q 2019 PloS one Table HIV K219E;K219Q 0;0 7;7 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. K65R 2019 PloS one Table HIV K65R 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. K70R 2019 PloS one Table HIV K70R 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. L210W 2019 PloS one Table HIV L210W 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. M184V 2019 PloS one Table HIV M184V 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. M41L 2019 PloS one Table HIV M41L 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. P225H 2019 PloS one Table HIV P225H 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. Q151M 2019 PloS one Table HIV Q151M 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. T215F 2019 PloS one Table HIV T215F 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. T215F/Y 2019 PloS one Table HIV T215F;T215Y 0;0 7;7 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. T69N 2019 PloS one Table HIV T69N 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. V106A 2019 PloS one Table HIV V106A 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. V108I 2019 PloS one Table HIV V108I 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. V118I 2019 PloS one Table HIV V118I 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. V179E 2019 PloS one Table HIV V179E 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. V75A 2019 PloS one Table HIV V75A 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. V90I 2019 PloS one Table HIV V90I 0 4 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. Y181C 2019 PloS one Table HIV Y181C 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. G190E 2019 Scientific reports Table HIV G190E 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. I47V 2019 Scientific reports Table HIV I47V 0 4 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. K101E 2019 Scientific reports Table HIV K101E 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. K103N 2019 Scientific reports Table HIV K103N 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. K219Q 2019 Scientific reports Table HIV K219Q 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. K219R 2019 Scientific reports Table HIV K219R 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. L100I 2019 Scientific reports Table HIV L100I 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. L210W 2019 Scientific reports Table HIV L210W 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. M41L 2019 Scientific reports Table HIV M41L 0 4 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. T215D 2019 Scientific reports Table HIV T215D 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. T215D/E 2019 Scientific reports Table HIV T215D;T215E 0;0 7;7 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. T215S 2019 Scientific reports Table HIV T215S 0 5 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. T69D 2019 Scientific reports Table HIV T69D 0 4 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. V32I 2019 Scientific reports Table HIV V32I 0 4 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560D 2019 Retrovirology Table HIV E560D 0 5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560G 2019 Retrovirology Table HIV E560G 0 5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560K 2019 Retrovirology Table HIV E560K 0 5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560K/D 2019 Retrovirology Table HIV E560D;E560K 0;0 7;7 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. G547D 2019 Retrovirology Table HIV G547D 0 5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. L544S 2019 Retrovirology Table HIV L544S 0 5 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. K103N 2020 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. K65R 2019 BMC public health Table HIV K65R 0 4 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. M184V 2019 Communications biology Table HIV M184V 0 5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). D30N 2020 EClinicalMedicine Table HIV D30N 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). D67G/N 2020 EClinicalMedicine Table HIV D67G;D67N 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). F116Y 2020 EClinicalMedicine Table HIV F116Y 0 5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). F53L/Y 2020 EClinicalMedicine Table HIV F53L;F53Y 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). F77L 2020 EClinicalMedicine Table HIV F77L 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). G151M 2020 EClinicalMedicine Table HIV G151M 0 5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). G190A/S 2020 EClinicalMedicine Table HIV G190A;G190S 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). G73S 2020 EClinicalMedicine Table HIV G73S 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). I50V/L 2020 EClinicalMedicine Table HIV I50L;I50V 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). I84V 2020 EClinicalMedicine Table HIV I84V 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). I85V 2020 EClinicalMedicine Table HIV I85V 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). K101E/Q 2020 EClinicalMedicine Table HIV K101E;K101Q 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). K103N/S 2020 EClinicalMedicine Table HIV K103N;K103S 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). K219E/Q 2020 EClinicalMedicine Table HIV K219E;K219Q 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). K65R 2020 EClinicalMedicine Table HIV K65R 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). K70R/E 2020 EClinicalMedicine Table HIV K70E;K70R 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). L100I 2020 EClinicalMedicine Table HIV L100I 0 5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). L210W 2020 EClinicalMedicine Table HIV L210W 0 5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). L23I 2020 EClinicalMedicine Table HIV L23I 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). L74I/V 2020 EClinicalMedicine Table HIV L74I;L74V 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). L76V 2020 EClinicalMedicine Table HIV L76V 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). L90M 2020 EClinicalMedicine Table HIV L90M 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). M184V/I 2020 EClinicalMedicine Table HIV M184I;M184V 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). M230L 2020 EClinicalMedicine Table HIV M230L 0 5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). M41L 2020 EClinicalMedicine Table HIV M41L 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). M46I/L 2020 EClinicalMedicine Table HIV M46I;M46L 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). N83D 2020 EClinicalMedicine Table HIV N83D 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). N88D/S 2020 EClinicalMedicine Table HIV N88D;N88S 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). P225H 2020 EClinicalMedicine Table HIV P225H 0 5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). T215F/I 2020 EClinicalMedicine Table HIV T215F;T215I 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). T69D/I 2020 EClinicalMedicine Table HIV T69D;T69I 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). V106A/M 2020 EClinicalMedicine Table HIV V106A;V106M 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). V179F/D 2020 EClinicalMedicine Table HIV V179D;V179F 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). V75M/T 2020 EClinicalMedicine Table HIV V75M;V75T 0;0 6;6 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). V82A 2020 EClinicalMedicine Table HIV V82A 0 4 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Y181C/V 2020 EClinicalMedicine Table HIV Y181C;Y181V 0;0 7;7 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Y188C/L 2020 EClinicalMedicine Table HIV Y188C;Y188L 0;0 7;7 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. M184V/I 2020 HIV medicine Table HIV M184I;M184V 0;0 7;7 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Q112D 2020 AIDS research and human retroviruses Table HIV Q112D 0 5 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. G190A 2020 EClinicalMedicine Table HIV G190A 0 5 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. K103N 2020 EClinicalMedicine Table HIV K103N 0 5 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. K65R 2020 EClinicalMedicine Table HIV K65R 0 4 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. M184V 2020 EClinicalMedicine Table HIV M184V 0 5 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Y181C 2020 EClinicalMedicine Table HIV Y181C 0 5 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. G190A 2020 European journal of medicinal chemistry Table HIV G190A 0 5 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. K103N 2020 European journal of medicinal chemistry Table HIV K103N 0 5 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. L100I 2020 European journal of medicinal chemistry Table HIV L100I 0 5 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. V108I 2020 European journal of medicinal chemistry Table HIV V108I 0 5 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Y181C 2020 European journal of medicinal chemistry Table HIV Y181C 0 5 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Y188L 2020 European journal of medicinal chemistry Table HIV Y188L 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. A21E 2020 AIDS research and therapy Table HIV A21E 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. A23V 2020 AIDS research and therapy Table HIV A23V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. A62V 2020 AIDS research and therapy Table HIV A62V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. A80V 2020 AIDS research and therapy Table HIV A80V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. D232E 2020 AIDS research and therapy Table HIV D232E 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. D253E 2020 AIDS research and therapy Table HIV D253E 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. D256E 2020 AIDS research and therapy Table HIV D256E 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. D25E 2020 AIDS research and therapy Table HIV D25E 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. D67N 2020 AIDS research and therapy Table HIV D67N 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E138A/K 2020 AIDS research and therapy Table HIV E138A;E138K 0;0 7;7 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E138D 2020 AIDS research and therapy Table HIV E138D 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E138G 2020 AIDS research and therapy Table HIV E138G 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E138K 2020 AIDS research and therapy Table HIV E138K 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E157Q 2020 AIDS research and therapy Table HIV E157Q 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E212L 2020 AIDS research and therapy Table HIV E212L 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E212V 2020 AIDS research and therapy Table HIV E212V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E44D 2020 AIDS research and therapy Table HIV E44D 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E69Q 2020 AIDS research and therapy Table HIV E69Q 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. E92Q 2020 AIDS research and therapy Table HIV E92Q 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. F116Y 2020 AIDS research and therapy Table HIV F116Y 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. F181L 2020 AIDS research and therapy Table HIV F181L 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. F227L 2020 AIDS research and therapy Table HIV F227L 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G106A 2020 AIDS research and therapy Table HIV G106A 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G140A 2020 AIDS research and therapy Table HIV G140A 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G140S 2020 AIDS research and therapy Table HIV G140S 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G163E 2020 AIDS research and therapy Table HIV G163E 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G163R 2020 AIDS research and therapy Table HIV G163R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G163T 2020 AIDS research and therapy Table HIV G163T 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G163V 2020 AIDS research and therapy Table HIV G163V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G190A 2020 AIDS research and therapy Table HIV G190A 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G193E 2020 AIDS research and therapy Table HIV G193E 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. G197W 2020 AIDS research and therapy Table HIV G197W 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. H221Y 2020 AIDS research and therapy Table HIV H221Y 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I113V 2020 AIDS research and therapy Table HIV I113V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I135V 2020 AIDS research and therapy Table HIV I135V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I141V 2020 AIDS research and therapy Table HIV I141V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I203M 2020 AIDS research and therapy Table HIV I203M 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I204V 2020 AIDS research and therapy Table HIV I204V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I208L 2020 AIDS research and therapy Table HIV I208L 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I208M 2020 AIDS research and therapy Table HIV I208M 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I220L 2020 AIDS research and therapy Table HIV I220L 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I47V 2020 AIDS research and therapy Table HIV I47V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I54L 2020 AIDS research and therapy Table HIV I54L 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I54M 2020 AIDS research and therapy Table HIV I54M 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I54V 2020 AIDS research and therapy Table HIV I54V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I72V 2020 AIDS research and therapy Table HIV I72V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I73T 2020 AIDS research and therapy Table HIV I73T 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I73V 2020 AIDS research and therapy Table HIV I73V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. I84V 2020 AIDS research and therapy Table HIV I84V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K103N 2020 AIDS research and therapy Table HIV K103N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K103S 2020 AIDS research and therapy Table HIV K103S 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K111R 2020 AIDS research and therapy Table HIV K111R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K111T 2020 AIDS research and therapy Table HIV K111T 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K136N 2020 AIDS research and therapy Table HIV K136N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K14R 2020 AIDS research and therapy Table HIV K14R 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K156N 2020 AIDS research and therapy Table HIV K156N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K156R 2020 AIDS research and therapy Table HIV K156R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K160N 2020 AIDS research and therapy Table HIV K160N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K160Q 2020 AIDS research and therapy Table HIV K160Q 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K160R 2020 AIDS research and therapy Table HIV K160R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K211R 2020 AIDS research and therapy Table HIV K211R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K215N 2020 AIDS research and therapy Table HIV K215N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K219E 2020 AIDS research and therapy Table HIV K219E 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K219N 2020 AIDS research and therapy Table HIV K219N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K219Q 2020 AIDS research and therapy Table HIV K219Q 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K219R 2020 AIDS research and therapy Table HIV K219R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K238T 2020 AIDS research and therapy Table HIV K238T 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K240R 2020 AIDS research and therapy Table HIV K240R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. K43T 2020 AIDS research and therapy Table HIV K43T 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L100I 2020 AIDS research and therapy Table HIV L100I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L101I 2020 AIDS research and therapy Table HIV L101I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L210W 2020 AIDS research and therapy Table HIV L210W 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L234F 2020 AIDS research and therapy Table HIV L234F 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L234I 2020 AIDS research and therapy Table HIV L234I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L234V 2020 AIDS research and therapy Table HIV L234V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L24I 2020 AIDS research and therapy Table HIV L24I 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L24M 2020 AIDS research and therapy Table HIV L24M 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L28I 2020 AIDS research and therapy Table HIV L28I 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L33F 2020 AIDS research and therapy Table HIV L33F 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L68M 2020 AIDS research and therapy Table HIV L68M 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L68V 2020 AIDS research and therapy Table HIV L68V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L74I 2020 AIDS research and therapy Table HIV L74I 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L74M 2020 AIDS research and therapy Table HIV L74M 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L74V 2020 AIDS research and therapy Table HIV L74V 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. L90M 2020 AIDS research and therapy Table HIV L90M 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. M184V 2020 AIDS research and therapy Table HIV M184V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. M230L 2020 AIDS research and therapy Table HIV M230L 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. M41L 2020 AIDS research and therapy Table HIV M41L 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. M46I 2020 AIDS research and therapy Table HIV M46I 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. M46L 2020 AIDS research and therapy Table HIV M46L 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. M50L 2020 AIDS research and therapy Table HIV M50L 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. N155H 2020 AIDS research and therapy Table HIV N155H 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. N222K 2020 AIDS research and therapy Table HIV N222K 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. P30A 2020 AIDS research and therapy Table HIV P30A 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Q148H 2020 AIDS research and therapy Table HIV Q148H 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Q148K 2020 AIDS research and therapy Table HIV Q148K 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Q151M 2020 AIDS research and therapy Table HIV Q151M 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Q44P 2020 AIDS research and therapy Table HIV Q44P 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Q58E 2020 AIDS research and therapy Table HIV Q58E 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. R187K 2020 AIDS research and therapy Table HIV R187K 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. R228K 2020 AIDS research and therapy Table HIV R228K 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S119P 2020 AIDS research and therapy Table HIV S119P 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S119R 2020 AIDS research and therapy Table HIV S119R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S119T 2020 AIDS research and therapy Table HIV S119T 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S123V 2020 AIDS research and therapy Table HIV S123V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S17N 2020 AIDS research and therapy Table HIV S17N 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S230N 2020 AIDS research and therapy Table HIV S230N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S230R 2020 AIDS research and therapy Table HIV S230R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S24N 2020 AIDS research and therapy Table HIV S24N 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S255N 2020 AIDS research and therapy Table HIV S255N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S283G 2020 AIDS research and therapy Table HIV S283G 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. S39C 2020 AIDS research and therapy Table HIV S39C 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T112A 2020 AIDS research and therapy Table HIV T112A 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T112I 2020 AIDS research and therapy Table HIV T112I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T112S 2020 AIDS research and therapy Table HIV T112S 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T112V 2020 AIDS research and therapy Table HIV T112V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T122S 2020 AIDS research and therapy Table HIV T122S 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T124A 2020 AIDS research and therapy Table HIV T124A 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T124N 2020 AIDS research and therapy Table HIV T124N 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T125A 2020 AIDS research and therapy Table HIV T125A 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T125V 2020 AIDS research and therapy Table HIV T125V 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T206S 2020 AIDS research and therapy Table HIV T206S 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T215A 2020 AIDS research and therapy Table HIV T215A 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T215D 2020 AIDS research and therapy Table HIV T215D 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T215Y 2020 AIDS research and therapy Table HIV T215Y 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T218S 2020 AIDS research and therapy Table HIV T218S 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T69D 2020 AIDS research and therapy Table HIV T69D 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T74P 2020 AIDS research and therapy Table HIV T74P 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. T97A 2020 AIDS research and therapy Table HIV T97A 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V108I 2020 AIDS research and therapy Table HIV V108I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V126T 2020 AIDS research and therapy Table HIV V126T 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V151I 2020 AIDS research and therapy Table HIV V151I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V179D 2020 AIDS research and therapy Table HIV V179D 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V179E 2020 AIDS research and therapy Table HIV V179E 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V201I 2020 AIDS research and therapy Table HIV V201I 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V31I 2020 AIDS research and therapy Table HIV V31I 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V32I 2020 AIDS research and therapy Table HIV V32I 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V75I 2020 AIDS research and therapy Table HIV V75I 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V82A 2020 AIDS research and therapy Table HIV V82A 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V82F 2020 AIDS research and therapy Table HIV V82F 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V82M 2020 AIDS research and therapy Table HIV V82M 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. V82T 2020 AIDS research and therapy Table HIV V82T 0 4 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. W243G 2020 AIDS research and therapy Table HIV W243G 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Y115F 2020 AIDS research and therapy Table HIV Y115F 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Y143C 2020 AIDS research and therapy Table HIV Y143C 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Y143H 2020 AIDS research and therapy Table HIV Y143H 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Y143R 2020 AIDS research and therapy Table HIV Y143R 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Y318F 2020 AIDS research and therapy Table HIV Y318F 0 5 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Y99F 2020 AIDS research and therapy Table HIV Y99F 0 4 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. A98G 2020 PloS one Table HIV A98G 0 4 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. E138A 2020 PloS one Table HIV E138A 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. E138G 2020 PloS one Table HIV E138G 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. G190A 2020 PloS one Table HIV G190A 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. I54V 2020 PloS one Table HIV I54V 0 4 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. K103N 2020 PloS one Table HIV K103N 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. K219R 2020 PloS one Table HIV K219R 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. K65R 2020 PloS one Table HIV K65R 0 4 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. L33F 2020 PloS one Table HIV L33F 0 4 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. M184I 2020 PloS one Table HIV M184I 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. M184V 2020 PloS one Table HIV M184V 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. V179D 2020 PloS one Table HIV V179D 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. V179E 2020 PloS one Table HIV V179E 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. V179T 2020 PloS one Table HIV V179T 0 5 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. Y181C 2020 PloS one Table HIV Y181C 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. F115Y 2020 Scientific reports Table HIV F115Y 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. F116Y 2020 Scientific reports Table HIV F116Y 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. F160L 2020 Scientific reports Table HIV F160L 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. F160M 2020 Scientific reports Table HIV F160M 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. G112S 2020 Scientific reports Table HIV G112S 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. L149I 2020 Scientific reports Table HIV L149I 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. L74V 2020 Scientific reports Table HIV L74V 0 4 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. M184V 2020 Scientific reports Table HIV M184V 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Q151M 2020 Scientific reports Table HIV Q151M 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Q182G 2020 Scientific reports Table HIV Q182G 0 5 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Y115F 2020 Scientific reports Table HIV Y115F 0 5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. G190S 2020 BMC infectious diseases Table HIV G190S 0 5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. K65R 2020 BMC infectious diseases Table HIV K65R 0 4 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. L228R 2020 BMC infectious diseases Table HIV L228R 0 5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. V179D 2020 BMC infectious diseases Table HIV V179D 0 5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. V179E 2020 BMC infectious diseases Table HIV V179E 0 5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Y115F 2020 BMC infectious diseases Table HIV Y115F 0 5 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Y181C 2020 BMC infectious diseases Table HIV Y181C 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. A98G 2020 The Journal of antimicrobial chemotherapy Table HIV A98G 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. D67N 2020 The Journal of antimicrobial chemotherapy Table HIV D67N 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. E44D 2020 The Journal of antimicrobial chemotherapy Table HIV E44D 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. G190A 2020 The Journal of antimicrobial chemotherapy Table HIV G190A 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. H221Y 2020 The Journal of antimicrobial chemotherapy Table HIV H221Y 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. I54V 2020 The Journal of antimicrobial chemotherapy Table HIV I54V 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K101E 2020 The Journal of antimicrobial chemotherapy Table HIV K101E 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K101H 2020 The Journal of antimicrobial chemotherapy Table HIV K101H 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K103N 2020 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K219E 2020 The Journal of antimicrobial chemotherapy Table HIV K219E 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K219Q 2020 The Journal of antimicrobial chemotherapy Table HIV K219Q 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K238T 2020 The Journal of antimicrobial chemotherapy Table HIV K238T 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K65R 2020 The Journal of antimicrobial chemotherapy Table HIV K65R 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K70E 2020 The Journal of antimicrobial chemotherapy Table HIV K70E 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. K70R 2020 The Journal of antimicrobial chemotherapy Table HIV K70R 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L10F 2020 The Journal of antimicrobial chemotherapy Table HIV L10F 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L24I 2020 The Journal of antimicrobial chemotherapy Table HIV L24I 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L33F 2020 The Journal of antimicrobial chemotherapy Table HIV L33F 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L74I 2020 The Journal of antimicrobial chemotherapy Table HIV L74I 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L74V 2020 The Journal of antimicrobial chemotherapy Table HIV L74V 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. L90M 2020 The Journal of antimicrobial chemotherapy Table HIV L90M 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. M184V 2020 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. M41L 2020 The Journal of antimicrobial chemotherapy Table HIV M41L 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. M46I 2020 The Journal of antimicrobial chemotherapy Table HIV M46I 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. N348I 2020 The Journal of antimicrobial chemotherapy Table HIV N348I 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. P225H 2020 The Journal of antimicrobial chemotherapy Table HIV P225H 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. T215F 2020 The Journal of antimicrobial chemotherapy Table HIV T215F 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. T215I 2020 The Journal of antimicrobial chemotherapy Table HIV T215I 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. T215Y 2020 The Journal of antimicrobial chemotherapy Table HIV T215Y 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. T69D 2020 The Journal of antimicrobial chemotherapy Table HIV T69D 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. V108I 2020 The Journal of antimicrobial chemotherapy Table HIV V108I 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. V179E 2020 The Journal of antimicrobial chemotherapy Table HIV V179E 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. V75I 2020 The Journal of antimicrobial chemotherapy Table HIV V75I 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. V75M 2020 The Journal of antimicrobial chemotherapy Table HIV V75M 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. V82A 2020 The Journal of antimicrobial chemotherapy Table HIV V82A 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. V82S 2020 The Journal of antimicrobial chemotherapy Table HIV V82S 0 4 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Y115F 2020 The Journal of antimicrobial chemotherapy Table HIV Y115F 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Y181C 2020 The Journal of antimicrobial chemotherapy Table HIV Y181C 0 5 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Y318F 2020 The Journal of antimicrobial chemotherapy Table HIV Y318F 0 5 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. E157Q 2020 Ethiopian journal of health sciences Table HIV E157Q 0 5 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. E92G 2020 Ethiopian journal of health sciences Table HIV E92G 0 4 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. E92V 2020 Ethiopian journal of health sciences Table HIV E92V 0 4 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. G140S/A 2020 Ethiopian journal of health sciences Table HIV G140A;G140S 0;0 7;7 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. L74M/I 2020 Ethiopian journal of health sciences Table HIV L74I;L74M 0;0 6;6 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. M50I 2020 Ethiopian journal of health sciences Table HIV M50I 0 4 32116431 Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya. T97A 2020 Ethiopian journal of health sciences Table HIV T97A 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. A98G 2020 PloS one Table HIV A98G 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. D67E 2020 PloS one Table HIV D67E 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. D67N 2020 PloS one Table HIV D67N 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. E138A 2020 PloS one Table HIV E138A 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. E138G/A 2020 PloS one Table HIV E138A;E138G 0;0 7;7 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. F77L 2020 PloS one Table HIV F77L 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. G190A/S 2020 PloS one Table HIV G190A;G190S 0;0 7;7 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. G73S 2020 PloS one Table HIV G73S 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. H221Y 2020 PloS one Table HIV H221Y 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. I47V 2020 PloS one Table HIV I47V 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. I50L 2020 PloS one Table HIV I50L 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. I54L/V 2020 PloS one Table HIV I54L;I54V 0;0 6;6 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K101E/R 2020 PloS one Table HIV K101E;K101R 0;0 7;7 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K103N 2020 PloS one Table HIV K103N 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K103N/S 2020 PloS one Table HIV K103N;K103S 0;0 7;7 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K20T 2020 PloS one Table HIV K20T 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K219E/Q 2020 PloS one Table HIV K219E;K219Q 0;0 7;7 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K238T/N 2020 PloS one Table HIV K238N;K238T 0;0 7;7 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K65I 2020 PloS one Table HIV K65I 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K65R/E 2020 PloS one Table HIV K65E;K65R 0;0 6;6 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K70I 2020 PloS one Table HIV K70I 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. K70R 2020 PloS one Table HIV K70R 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L100V 2020 PloS one Table HIV L100V 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L10F 2020 PloS one Table HIV L10F 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L10I 2020 PloS one Table HIV L10I 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L10V 2020 PloS one Table HIV L10V 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L210W 2020 PloS one Table HIV L210W 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L33F 2020 PloS one Table HIV L33F 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L74V 2020 PloS one Table HIV L74V 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L76V 2020 PloS one Table HIV L76V 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. L89V 2020 PloS one Table HIV L89V 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. M184V 2020 PloS one Table HIV M184V 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. M230L 2020 PloS one Table HIV M230L 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. M41L 2020 PloS one Table HIV M41L 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. M46I 2020 PloS one Table HIV M46I 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. N348I 2020 PloS one Table HIV N348I 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. P225H 2020 PloS one Table HIV P225H 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. P236L 2020 PloS one Table HIV P236L 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. Q58E 2020 PloS one Table HIV Q58E 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. T215F/I 2020 PloS one Table HIV T215F;T215I 0;0 7;7 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. T215N 2020 PloS one Table HIV T215N 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V106A 2020 PloS one Table HIV V106A 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V106I 2020 PloS one Table HIV V106I 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V106M 2020 PloS one Table HIV V106M 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V108I 2020 PloS one Table HIV V108I 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V179T 2020 PloS one Table HIV V179T 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V32I 2020 PloS one Table HIV V32I 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. V75M 2020 PloS one Table HIV V75M 0 4 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. Y115F 2020 PloS one Table HIV Y115F 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. Y181C 2020 PloS one Table HIV Y181C 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. Y181N 2020 PloS one Table HIV Y181N 0 5 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. Y188L/H 2020 PloS one Table HIV Y188H;Y188L 0;0 7;7 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. A389T 2020 Pathogens (Basel, Switzerland) Table HIV A389T 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. A6736G 2020 Pathogens (Basel, Switzerland) Table HIV A6736G 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. A6777G 2020 Pathogens (Basel, Switzerland) Table HIV A6777G 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. A6843G 2020 Pathogens (Basel, Switzerland) Table HIV A6843G 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. A6897G 2020 Pathogens (Basel, Switzerland) Table HIV A6897G 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. A7048C 2020 Pathogens (Basel, Switzerland) Table HIV A7048C 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. A7647G 2020 Pathogens (Basel, Switzerland) Table HIV A7647G 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. C7219T 2020 Pathogens (Basel, Switzerland) Table HIV C7219T 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. D282N 2020 Pathogens (Basel, Switzerland) Table HIV D282N 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. G6907A 2020 Pathogens (Basel, Switzerland) Table HIV G6907A 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. G7182A 2020 Pathogens (Basel, Switzerland) Table HIV G7182A 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. G7503A 2020 Pathogens (Basel, Switzerland) Table HIV G7503A 0 6 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. K187E 2020 Pathogens (Basel, Switzerland) Table HIV K187E 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. N133S 2020 Pathogens (Basel, Switzerland) Table HIV N133S 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. N169D 2020 Pathogens (Basel, Switzerland) Table HIV N169D 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. N237T 2020 Pathogens (Basel, Switzerland) Table HIV N237T 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. S147G 2020 Pathogens (Basel, Switzerland) Table HIV S147G 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. S190N 2020 Pathogens (Basel, Switzerland) Table HIV S190N 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. S294F 2020 Pathogens (Basel, Switzerland) Table HIV S294F 0 5 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. T437A 2020 Pathogens (Basel, Switzerland) Table HIV T437A 0 5 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. K103N 2020 Acta pharmaceutica Sinica. B Table HIV K103N 0 5 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. L74V 2020 Acta pharmaceutica Sinica. B Table HIV L74V 0 4 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. M184V 2020 Acta pharmaceutica Sinica. B Table HIV M184V 0 5 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. V82F 2020 Acta pharmaceutica Sinica. B Table HIV V82F 0 4 32140396 Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimi din-4(3H)-ones as potential HIV-1 inhibitors. Y181C 2020 Acta pharmaceutica Sinica. B Table HIV Y181C 0 5 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. N74D 2020 Virology journal Table HIV N74D 0 4 32158555 Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy. E138A 2020 Southern African journal of HIV medicine Table HIV E138A 0 5 32158555 Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy. K103N 2020 Southern African journal of HIV medicine Table HIV K103N 0 5 32158555 Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy. V106M 2020 Southern African journal of HIV medicine Table HIV V106M 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. F53L 2020 Virology journal Table HIV F53L 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. G190A 2020 Virology journal Table HIV G190A 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. I54L 2020 Virology journal Table HIV I54L 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. I84V 2020 Virology journal Table HIV I84V 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K101E 2020 Virology journal Table HIV K101E 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K103N/S 2020 Virology journal Table HIV K103N;K103S 0;0 7;7 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K65R 2020 Virology journal Table HIV K65R 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K70Q/R 2020 Virology journal Table HIV K70Q;K70R 0;0 6;6 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K70R/E 2020 Virology journal Table HIV K70E;K70R 0;0 6;6 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. L100I 2020 Virology journal Table HIV L100I 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. L210W 2020 Virology journal Table HIV L210W 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. L74I 2020 Virology journal Table HIV L74I 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. L76V 2020 Virology journal Table HIV L76V 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. L90M 2020 Virology journal Table HIV L90M 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. M184V/I 2020 Virology journal Table HIV M184I;M184V 0;0 7;7 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. M230L 2020 Virology journal Table HIV M230L 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. M41L 2020 Virology journal Table HIV M41L 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. M46I/L 2020 Virology journal Table HIV M46I;M46L 0;0 6;6 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. P225H 2020 Virology journal Table HIV P225H 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. T215D/S 2020 Virology journal Table HIV T215D;T215S 0;0 7;7 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. T69S/D 2020 Virology journal Table HIV T69D;T69S 0;0 6;6 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. V106M/A 2020 Virology journal Table HIV V106A;V106M 0;0 7;7 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. V108I 2020 Virology journal Table HIV V108I 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. V82L 2020 Virology journal Table HIV V82L 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. Y115F 2020 Virology journal Table HIV Y115F 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. Y181C 2020 Virology journal Table HIV Y181C 0 5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. Y188H 2020 Virology journal Table HIV Y188H 0 5 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. A14C 2020 Cell reports Table HIV A14C 0 4 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. A92E 2020 Cell reports Table HIV A92E 0 4 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. E45C 2020 Cell reports Table HIV E45C 0 4 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. G89V 2020 Cell reports Table HIV G89V 0 4 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. G94D 2020 Cell reports Table HIV G94D 0 4 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. P90A 2020 Cell reports Table HIV P90A 0 4 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. G40E 2020 Scientific reports Table HIV G40E 0 4 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. G40R 2020 Scientific reports Table HIV G40R 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. D67N 2020 Frontiers in microbiology Table HIV D67N 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. E157Q 2020 Frontiers in microbiology Table HIV E157Q 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. G190A/S 2020 Frontiers in microbiology Table HIV G190A;G190S 0;0 7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. H221Y 2020 Frontiers in microbiology Table HIV H221Y 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. I47A 2020 Frontiers in microbiology Table HIV I47A 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. I50L/V 2020 Frontiers in microbiology Table HIV I50L;I50V 0;0 6;6 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. I54V 2020 Frontiers in microbiology Table HIV I54V 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. I84V 2020 Frontiers in microbiology Table HIV I84V 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. K103N/S 2020 Frontiers in microbiology Table HIV K103N;K103S 0;0 7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. K219E/Q 2020 Frontiers in microbiology Table HIV K219E;K219Q 0;0 7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. K65R/N 2020 Frontiers in microbiology Table HIV K65N;K65R 0;0 6;6 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. K70R 2020 Frontiers in microbiology Table HIV K70R 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. K70R/E 2020 Frontiers in microbiology Table HIV K70E;K70R 0;0 6;6 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. L100I 2020 Frontiers in microbiology Table HIV L100I 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. L210W 2020 Frontiers in microbiology Table HIV L210W 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. L74V 2020 Frontiers in microbiology Table HIV L74V 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. L76V 2020 Frontiers in microbiology Table HIV L76V 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M184V 2020 Frontiers in microbiology Table HIV M184V 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M184V/I 2020 Frontiers in microbiology Table HIV M184I;M184V 0;0 7;7 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M230L 2020 Frontiers in microbiology Table HIV M230L 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M41L 2020 Frontiers in microbiology Table HIV M41L 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M46I 2020 Frontiers in microbiology Table HIV M46I 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. P225H 2020 Frontiers in microbiology Table HIV P225H 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. T215Y 2020 Frontiers in microbiology Table HIV T215Y 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. T66I 2020 Frontiers in microbiology Table HIV T66I 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. T69D 2020 Frontiers in microbiology Table HIV T69D 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. T97A 2020 Frontiers in microbiology Table HIV T97A 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. V106M 2020 Frontiers in microbiology Table HIV V106M 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. V108I 2020 Frontiers in microbiology Table HIV V108I 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. V32I 2020 Frontiers in microbiology Table HIV V32I 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. V82A 2020 Frontiers in microbiology Table HIV V82A 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Y115F 2020 Frontiers in microbiology Table HIV Y115F 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Y143R 2020 Frontiers in microbiology Table HIV Y143R 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Y181C 2020 Frontiers in microbiology Table HIV Y181C 0 5 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Y188L 2020 Frontiers in microbiology Table HIV Y188L 0 5 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. C67E 2020 PloS one Table HIV C67E 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. C67S 2020 PloS one Table HIV C67S 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. C95W 2020 PloS one Table HIV C95W 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. E35D 2020 PloS one Table HIV E35D 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. E35Q 2020 PloS one Table HIV E35Q 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. E65D 2020 PloS one Table HIV E65D 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. F99S 2020 PloS one Table HIV F99S 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. G16E 2020 PloS one Table HIV G16E 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. G17E 2020 PloS one Table HIV G17E 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. G86L 2020 PloS one Table HIV G86L 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. G94I 2020 PloS one Table HIV G94I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. G94R 2020 PloS one Table HIV G94R 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. G94R/I 2020 PloS one Table HIV G94I;G94R 0;0 6;6 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. H69K 2020 PloS one Table HIV H69K 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. H69K/R 2020 PloS one Table HIV H69K;H69R 0;0 6;6 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. H69R 2020 PloS one Table HIV H69R 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I13A 2020 PloS one Table HIV I13A 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I13V 2020 PloS one Table HIV I13V 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I15V 2020 PloS one Table HIV I15V 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I62V 2020 PloS one Table HIV I62V 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I64L 2020 PloS one Table HIV I64L 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I64L/M 2020 PloS one Table HIV I64L;I64M 0;0 6;6 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I64M 2020 PloS one Table HIV I64M 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I72M 2020 PloS one Table HIV I72M 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I72T 2020 PloS one Table HIV I72T 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I72V 2020 PloS one Table HIV I72V 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. K14R 2020 PloS one Table HIV K14R 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. K20I 2020 PloS one Table HIV K20I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. K43R 2020 PloS one Table HIV K43R 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. K45R 2020 PloS one Table HIV K45R 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. K70R 2020 PloS one Table HIV K70R 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L10I 2020 PloS one Table HIV L10I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L10M 2020 PloS one Table HIV L10M 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L10V 2020 PloS one Table HIV L10V 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L19I 2020 PloS one Table HIV L19I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L19P 2020 PloS one Table HIV L19P 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L33F 2020 PloS one Table HIV L33F 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L38I 2020 PloS one Table HIV L38I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L63P 2020 PloS one Table HIV L63P 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L63Q 2020 PloS one Table HIV L63Q 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L63S 2020 PloS one Table HIV L63S 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L63T 2020 PloS one Table HIV L63T 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L63T/P 2020 PloS one Table HIV L63P;L63T 0;0 6;6 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L97K 2020 PloS one Table HIV L97K 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. L97V 2020 PloS one Table HIV L97V 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. M31I 2020 PloS one Table HIV M31I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. M36I 2020 PloS one Table HIV M36I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. M36I/L 2020 PloS one Table HIV M36I;M36L 0;0 6;6 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. M36L 2020 PloS one Table HIV M36L 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. M46L 2020 PloS one Table HIV M46L 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. N37D 2020 PloS one Table HIV N37D 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. N37E 2020 PloS one Table HIV N37E 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. N37H 2020 PloS one Table HIV N37H 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. N37S 2020 PloS one Table HIV N37S 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. N88D 2020 PloS one Table HIV N88D 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. N98H 2020 PloS one Table HIV N98H 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. P79S 2020 PloS one Table HIV P79S 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Q61X 2020 PloS one Table HIV Q61X 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Q92H 2020 PloS one Table HIV Q92H 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Q92W 2020 PloS one Table HIV Q92W 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Q92W/H 2020 PloS one Table HIV Q92H;Q92W 0;0 6;6 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. R41K 2020 PloS one Table HIV R41K 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. R57K 2020 PloS one Table HIV R57K 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. R57K/G 2020 PloS one Table HIV R57G;R57K 0;0 6;6 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. R59G 2020 PloS one Table HIV R59G 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. R87L 2020 PloS one Table HIV R87L 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. T12A 2020 PloS one Table HIV T12A 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. T91C 2020 PloS one Table HIV T91C 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. T96A 2020 PloS one Table HIV T96A 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. V82I 2020 PloS one Table HIV V82I 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. V82L 2020 PloS one Table HIV V82L 0 4 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. E138A 2020 BMC infectious diseases Table HIV E138A 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. H221Y 2020 BMC infectious diseases Table HIV H221Y 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. K103R 2020 BMC infectious diseases Table HIV K103R 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. V179D 2020 BMC infectious diseases Table HIV V179D 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. V179E 2020 BMC infectious diseases Table HIV V179E 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Y181C 2020 BMC infectious diseases Table HIV Y181C 0 5 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. K101E 2020 Scientific reports Table HIV K101E 0 5 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. K103N 2020 Scientific reports Table HIV K103N 0 5 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. K103R 2020 Scientific reports Table HIV K103R 0 5 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. M46I 2020 Scientific reports Table HIV M46I 0 4 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. M46L 2020 Scientific reports Table HIV M46L 0 4 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. M46R 2020 Scientific reports Table HIV M46R 0 4 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. N88S 2020 Scientific reports Table HIV N88S 0 4 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Q58E 2020 Scientific reports Table HIV Q58E 0 4 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. V106I 2020 Scientific reports Table HIV V106I 0 5 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. V179D 2020 Scientific reports Table HIV V179D 0 5 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. V179E 2020 Scientific reports Table HIV V179E 0 5 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. V179T 2020 Scientific reports Table HIV V179T 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. E138A 2020 PloS one Table HIV E138A 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. E138K 2020 PloS one Table HIV E138K 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. E138T 2020 PloS one Table HIV E138T 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. E92Q 2020 PloS one Table HIV E92Q 0 4 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. G140A 2020 PloS one Table HIV G140A 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. G140C 2020 PloS one Table HIV G140C 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. G140S 2020 PloS one Table HIV G140S 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. N155H 2020 PloS one Table HIV N155H 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Q148H 2020 PloS one Table HIV Q148H 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Q148K 2020 PloS one Table HIV Q148K 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Q148N 2020 PloS one Table HIV Q148N 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Q148R 2020 PloS one Table HIV Q148R 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. R263K 2020 PloS one Table HIV R263K 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. S147G 2020 PloS one Table HIV S147G 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. T66A 2020 PloS one Table HIV T66A 0 4 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. T66I 2020 PloS one Table HIV T66I 0 4 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. T66K 2020 PloS one Table HIV T66K 0 4 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Y143C 2020 PloS one Table HIV Y143C 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Y143H 2020 PloS one Table HIV Y143H 0 5 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Y143R 2020 PloS one Table HIV Y143R 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. A62V 2020 Epidemiology and infection Table HIV A62V 0 4 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. E138A 2020 Epidemiology and infection Table HIV E138A 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. G190A 2020 Epidemiology and infection Table HIV G190A 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. H221Y 2020 Epidemiology and infection Table HIV H221Y 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. K101E 2020 Epidemiology and infection Table HIV K101E 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. K103N 2020 Epidemiology and infection Table HIV K103N 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. K20T 2020 Epidemiology and infection Table HIV K20T 0 4 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. L33F 2020 Epidemiology and infection Table HIV L33F 0 4 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. M41L 2020 Epidemiology and infection Table HIV M41L 0 4 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. P225H 2020 Epidemiology and infection Table HIV P225H 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. T215D 2020 Epidemiology and infection Table HIV T215D 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. T69D 2020 Epidemiology and infection Table HIV T69D 0 4 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. V106I 2020 Epidemiology and infection Table HIV V106I 0 5 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. V179E/T 2020 Epidemiology and infection Table HIV V179E;V179T 0;0 7;7 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Y188L/N 2020 Epidemiology and infection Table HIV Y188L;Y188N 0;0 7;7 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). K65R/E 2020 EBioMedicine Table HIV K65E;K65R 0;0 6;6 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). L210W 2020 EBioMedicine Table HIV L210W 0 5 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). M184V 2020 EBioMedicine Table HIV M184V 0 5 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). M184V/I 2020 EBioMedicine Table HIV M184I;M184V 0;0 7;7 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). T215D 2020 EBioMedicine Table HIV T215D 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. E138A 2020 Antiviral chemistry & chemotherapy Table HIV E138A 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. E138K 2020 Antiviral chemistry & chemotherapy Table HIV E138K 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. E138Q 2020 Antiviral chemistry & chemotherapy Table HIV E138Q 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. E157Q 2020 Antiviral chemistry & chemotherapy Table HIV E157Q 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. G118R 2020 Antiviral chemistry & chemotherapy Table HIV G118R 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. G190S 2020 Antiviral chemistry & chemotherapy Table HIV G190S 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. K101E 2020 Antiviral chemistry & chemotherapy Table HIV K101E 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. K70E 2020 Antiviral chemistry & chemotherapy Table HIV K70E 0 4 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. M184V 2020 Antiviral chemistry & chemotherapy Table HIV M184V 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. N155H 2020 Antiviral chemistry & chemotherapy Table HIV N155H 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. S230R 2020 Antiviral chemistry & chemotherapy Table HIV S230R 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. T66I 2020 Antiviral chemistry & chemotherapy Table HIV T66I 0 4 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. T97A 2020 Antiviral chemistry & chemotherapy Table HIV T97A 0 4 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Y143C 2020 Antiviral chemistry & chemotherapy Table HIV Y143C 0 5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Y181C 2020 Antiviral chemistry & chemotherapy Table HIV Y181C 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. A98G 2020 AIDS research and therapy Table HIV A98G 0 4 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. E138A 2020 AIDS research and therapy Table HIV E138A 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. E138G 2020 AIDS research and therapy Table HIV E138G 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. E138K 2020 AIDS research and therapy Table HIV E138K 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. G190A 2020 AIDS research and therapy Table HIV G190A 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. H221Y 2020 AIDS research and therapy Table HIV H221Y 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. K101E 2020 AIDS research and therapy Table HIV K101E 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. K103N 2020 AIDS research and therapy Table HIV K103N 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. K103S 2020 AIDS research and therapy Table HIV K103S 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. K20T 2020 AIDS research and therapy Table HIV K20T 0 4 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. K238T 2020 AIDS research and therapy Table HIV K238T 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. M184V 2020 AIDS research and therapy Table HIV M184V 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. M46L 2020 AIDS research and therapy Table HIV M46L 0 4 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. M46V 2020 AIDS research and therapy Table HIV M46V 0 4 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. N88D 2020 AIDS research and therapy Table HIV N88D 0 4 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. Q58E 2020 AIDS research and therapy Table HIV Q58E 0 4 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. T47S 2020 AIDS research and therapy Table HIV T47S 0 4 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. V106M 2020 AIDS research and therapy Table HIV V106M 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. V108I 2020 AIDS research and therapy Table HIV V108I 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. V138Q 2020 AIDS research and therapy Table HIV V138Q 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. V179D 2020 AIDS research and therapy Table HIV V179D 0 5 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. Y181C 2020 AIDS research and therapy Table HIV Y181C 0 5 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. F227L 2020 Acta pharmaceutica Sinica. B Table HIV F227L 0 5 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. K103N 2020 Acta pharmaceutica Sinica. B Table HIV K103N 0 5 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. L100I 2020 Acta pharmaceutica Sinica. B Table HIV L100I 0 5 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. V106A 2020 Acta pharmaceutica Sinica. B Table HIV V106A 0 5 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Y188L 2020 Acta pharmaceutica Sinica. B Table HIV Y188L 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. A98S 2020 PloS one Table HIV A98S 0 4 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. E138S 2020 PloS one Table HIV E138S 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. G190A 2020 PloS one Table HIV G190A 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. K103N 2020 PloS one Table HIV K103N 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. K103R 2020 PloS one Table HIV K103R 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. K65R 2020 PloS one Table HIV K65R 0 4 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. M184V 2020 PloS one Table HIV M184V 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. M230L 2020 PloS one Table HIV M230L 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. V106M 2020 PloS one Table HIV V106M 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. V179I 2020 PloS one Table HIV V179I 0 5 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. Y188H 2020 PloS one Table HIV Y188H 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A115V 2020 The Journal of antimicrobial chemotherapy Table HIV A115V 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A146P 2020 The Journal of antimicrobial chemotherapy Table HIV A146P 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A179T 2020 The Journal of antimicrobial chemotherapy Table HIV A179T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A209T 2020 The Journal of antimicrobial chemotherapy Table HIV A209T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A326S 2020 The Journal of antimicrobial chemotherapy Table HIV A326S 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A340G 2020 The Journal of antimicrobial chemotherapy Table HIV A340G 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A374P 2020 The Journal of antimicrobial chemotherapy Table HIV A374P 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A71V 2020 The Journal of antimicrobial chemotherapy Table HIV A71V 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. A83S 2020 The Journal of antimicrobial chemotherapy Table HIV A83S 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. C330F 2020 The Journal of antimicrobial chemotherapy Table HIV C330F 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. D121N 2020 The Journal of antimicrobial chemotherapy Table HIV D121N 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. D425E 2020 The Journal of antimicrobial chemotherapy Table HIV D425E 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. D480E 2020 The Journal of antimicrobial chemotherapy Table HIV D480E 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E107G 2020 The Journal of antimicrobial chemotherapy Table HIV E107G 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E203D 2020 The Journal of antimicrobial chemotherapy Table HIV E203D 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E260D 2020 The Journal of antimicrobial chemotherapy Table HIV E260D 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E312D 2020 The Journal of antimicrobial chemotherapy Table HIV E312D 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E35D 2020 The Journal of antimicrobial chemotherapy Table HIV E35D 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E398Q 2020 The Journal of antimicrobial chemotherapy Table HIV E398Q 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E460A 2020 The Journal of antimicrobial chemotherapy Table HIV E460A 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E461G 2020 The Journal of antimicrobial chemotherapy Table HIV E461G 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E461K 2020 The Journal of antimicrobial chemotherapy Table HIV E461K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E477D 2020 The Journal of antimicrobial chemotherapy Table HIV E477D 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E477G 2020 The Journal of antimicrobial chemotherapy Table HIV E477G 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E53D 2020 The Journal of antimicrobial chemotherapy Table HIV E53D 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E55D 2020 The Journal of antimicrobial chemotherapy Table HIV E55D 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E55G 2020 The Journal of antimicrobial chemotherapy Table HIV E55G 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E65D 2020 The Journal of antimicrobial chemotherapy Table HIV E65D 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E93D 2020 The Journal of antimicrobial chemotherapy Table HIV E93D 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. E99A 2020 The Journal of antimicrobial chemotherapy Table HIV E99A 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. G248A 2020 The Journal of antimicrobial chemotherapy Table HIV G248A 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. G248T 2020 The Journal of antimicrobial chemotherapy Table HIV G248T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. G357S 2020 The Journal of antimicrobial chemotherapy Table HIV G357S 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. G62E 2020 The Journal of antimicrobial chemotherapy Table HIV G62E 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. G62Q 2020 The Journal of antimicrobial chemotherapy Table HIV G62Q 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. H124K 2020 The Journal of antimicrobial chemotherapy Table HIV H124K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. H69R 2020 The Journal of antimicrobial chemotherapy Table HIV H69R 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I147L 2020 The Journal of antimicrobial chemotherapy Table HIV I147L 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I15V 2020 The Journal of antimicrobial chemotherapy Table HIV I15V 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I223V 2020 The Journal of antimicrobial chemotherapy Table HIV I223V 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I34L 2020 The Journal of antimicrobial chemotherapy Table HIV I34L 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I376M 2020 The Journal of antimicrobial chemotherapy Table HIV I376M 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I479P 2020 The Journal of antimicrobial chemotherapy Table HIV I479P 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I479T 2020 The Journal of antimicrobial chemotherapy Table HIV I479T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I62V 2020 The Journal of antimicrobial chemotherapy Table HIV I62V 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I64V 2020 The Journal of antimicrobial chemotherapy Table HIV I64V 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. I93L 2020 The Journal of antimicrobial chemotherapy Table HIV I93L 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K103R 2020 The Journal of antimicrobial chemotherapy Table HIV K103R 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K110C 2020 The Journal of antimicrobial chemotherapy Table HIV K110C 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K113Q 2020 The Journal of antimicrobial chemotherapy Table HIV K113Q 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K18R 2020 The Journal of antimicrobial chemotherapy Table HIV K18R 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K20T 2020 The Journal of antimicrobial chemotherapy Table HIV K20T 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K26N 2020 The Journal of antimicrobial chemotherapy Table HIV K26N 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K28Q 2020 The Journal of antimicrobial chemotherapy Table HIV K28Q 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K30Q 2020 The Journal of antimicrobial chemotherapy Table HIV K30Q 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K30R 2020 The Journal of antimicrobial chemotherapy Table HIV K30R 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K388R 2020 The Journal of antimicrobial chemotherapy Table HIV K388R 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K411R 2020 The Journal of antimicrobial chemotherapy Table HIV K411R 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K418R 2020 The Journal of antimicrobial chemotherapy Table HIV K418R 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K481Q 2020 The Journal of antimicrobial chemotherapy Table HIV K481Q 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K95R 2020 The Journal of antimicrobial chemotherapy Table HIV K95R 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. K95T 2020 The Journal of antimicrobial chemotherapy Table HIV K95T 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L10V 2020 The Journal of antimicrobial chemotherapy Table HIV L10V 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L268M 2020 The Journal of antimicrobial chemotherapy Table HIV L268M 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L483I 2020 The Journal of antimicrobial chemotherapy Table HIV L483I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L483K 2020 The Journal of antimicrobial chemotherapy Table HIV L483K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L486W 2020 The Journal of antimicrobial chemotherapy Table HIV L486W 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L61I 2020 The Journal of antimicrobial chemotherapy Table HIV L61I 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L63P 2020 The Journal of antimicrobial chemotherapy Table HIV L63P 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. L78V 2020 The Journal of antimicrobial chemotherapy Table HIV L78V 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. M228I 2020 The Journal of antimicrobial chemotherapy Table HIV M228I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. M347S 2020 The Journal of antimicrobial chemotherapy Table HIV M347S 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. M36I 2020 The Journal of antimicrobial chemotherapy Table HIV M36I 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. M377L 2020 The Journal of antimicrobial chemotherapy Table HIV M377L 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. M378V 2020 The Journal of antimicrobial chemotherapy Table HIV M378V 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N126R 2020 The Journal of antimicrobial chemotherapy Table HIV N126R 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N131H 2020 The Journal of antimicrobial chemotherapy Table HIV N131H 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N252S 2020 The Journal of antimicrobial chemotherapy Table HIV N252S 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N372G 2020 The Journal of antimicrobial chemotherapy Table HIV N372G 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N37D 2020 The Journal of antimicrobial chemotherapy Table HIV N37D 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N37H 2020 The Journal of antimicrobial chemotherapy Table HIV N37H 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N37S 2020 The Journal of antimicrobial chemotherapy Table HIV N37S 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N37T 2020 The Journal of antimicrobial chemotherapy Table HIV N37T 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. N382H 2020 The Journal of antimicrobial chemotherapy Table HIV N382H 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. P255A 2020 The Journal of antimicrobial chemotherapy Table HIV P255A 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. P478S 2020 The Journal of antimicrobial chemotherapy Table HIV P478S 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. P478T 2020 The Journal of antimicrobial chemotherapy Table HIV P478T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. P497Q 2020 The Journal of antimicrobial chemotherapy Table HIV P497Q 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Q117L 2020 The Journal of antimicrobial chemotherapy Table HIV Q117L 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Q199E 2020 The Journal of antimicrobial chemotherapy Table HIV Q199E 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Q386P 2020 The Journal of antimicrobial chemotherapy Table HIV Q386P 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Q476P 2020 The Journal of antimicrobial chemotherapy Table HIV Q476P 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Q69K 2020 The Journal of antimicrobial chemotherapy Table HIV Q69K 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Q90K 2020 The Journal of antimicrobial chemotherapy Table HIV Q90K 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R15K 2020 The Journal of antimicrobial chemotherapy Table HIV R15K 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R15Q 2020 The Journal of antimicrobial chemotherapy Table HIV R15Q 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R20Q 2020 The Journal of antimicrobial chemotherapy Table HIV R20Q 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R286K 2020 The Journal of antimicrobial chemotherapy Table HIV R286K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R380K 2020 The Journal of antimicrobial chemotherapy Table HIV R380K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R384G 2020 The Journal of antimicrobial chemotherapy Table HIV R384G 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R387K 2020 The Journal of antimicrobial chemotherapy Table HIV R387K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R406K 2020 The Journal of antimicrobial chemotherapy Table HIV R406K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R41K 2020 The Journal of antimicrobial chemotherapy Table HIV R41K 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R429K 2020 The Journal of antimicrobial chemotherapy Table HIV R429K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R464K 2020 The Journal of antimicrobial chemotherapy Table HIV R464K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R490K 2020 The Journal of antimicrobial chemotherapy Table HIV R490K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R57K 2020 The Journal of antimicrobial chemotherapy Table HIV R57K 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R58K 2020 The Journal of antimicrobial chemotherapy Table HIV R58K 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R91G 2020 The Journal of antimicrobial chemotherapy Table HIV R91G 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R91K 2020 The Journal of antimicrobial chemotherapy Table HIV R91K 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. R91N 2020 The Journal of antimicrobial chemotherapy Table HIV R91N 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S111I 2020 The Journal of antimicrobial chemotherapy Table HIV S111I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S125N 2020 The Journal of antimicrobial chemotherapy Table HIV S125N 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S148T 2020 The Journal of antimicrobial chemotherapy Table HIV S148T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S165N 2020 The Journal of antimicrobial chemotherapy Table HIV S165N 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S173T 2020 The Journal of antimicrobial chemotherapy Table HIV S173T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S310T 2020 The Journal of antimicrobial chemotherapy Table HIV S310T 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S465F 2020 The Journal of antimicrobial chemotherapy Table HIV S465F 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S465L 2020 The Journal of antimicrobial chemotherapy Table HIV S465L 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S54A 2020 The Journal of antimicrobial chemotherapy Table HIV S54A 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S67A 2020 The Journal of antimicrobial chemotherapy Table HIV S67A 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T122P 2020 The Journal of antimicrobial chemotherapy Table HIV T122P 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T242N 2020 The Journal of antimicrobial chemotherapy Table HIV T242N 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T280A 2020 The Journal of antimicrobial chemotherapy Table HIV T280A 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T280V 2020 The Journal of antimicrobial chemotherapy Table HIV T280V 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T303V 2020 The Journal of antimicrobial chemotherapy Table HIV T303V 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T318K 2020 The Journal of antimicrobial chemotherapy Table HIV T318K 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T375N 2020 The Journal of antimicrobial chemotherapy Table HIV T375N 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T375V 2020 The Journal of antimicrobial chemotherapy Table HIV T375V 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T401L 2020 The Journal of antimicrobial chemotherapy Table HIV T401L 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T456I 2020 The Journal of antimicrobial chemotherapy Table HIV T456I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T456S 2020 The Journal of antimicrobial chemotherapy Table HIV T456S 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T470A 2020 The Journal of antimicrobial chemotherapy Table HIV T470A 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T471I 2020 The Journal of antimicrobial chemotherapy Table HIV T471I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T84V 2020 The Journal of antimicrobial chemotherapy Table HIV T84V 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. T97P 2020 The Journal of antimicrobial chemotherapy Table HIV T97P 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. V159I 2020 The Journal of antimicrobial chemotherapy Table HIV V159I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. V168I 2020 The Journal of antimicrobial chemotherapy Table HIV V168I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. V215M 2020 The Journal of antimicrobial chemotherapy Table HIV V215M 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. V390I 2020 The Journal of antimicrobial chemotherapy Table HIV V390I 0 5 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. V77I 2020 The Journal of antimicrobial chemotherapy Table HIV V77I 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. V7L 2020 The Journal of antimicrobial chemotherapy Table HIV V7L 0 3 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. V82I 2020 The Journal of antimicrobial chemotherapy Table HIV V82I 0 4 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Y484S 2020 The Journal of antimicrobial chemotherapy Table HIV Y484S 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. E138A 2020 PloS one Table HIV E138A 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. E138G 2020 PloS one Table HIV E138G 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K103N 2020 PloS one Table HIV K103N 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K219R 2020 PloS one Table HIV K219R 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K238T 2020 PloS one Table HIV K238T 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K65R 2020 PloS one Table HIV K65R 0 4 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K70E 2020 PloS one Table HIV K70E 0 4 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. M184I 2020 PloS one Table HIV M184I 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. M184V 2020 PloS one Table HIV M184V 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. M230L 2020 PloS one Table HIV M230L 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. M41L 2020 PloS one Table HIV M41L 0 4 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. P225H 2020 PloS one Table HIV P225H 0 5 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. V179E 2020 PloS one Table HIV V179E 0 5 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. E138A 2020 Virology journal Table HIV E138A 0 5 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. F77L 2020 Virology journal Table HIV F77L 0 4 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. K65R 2020 Virology journal Table HIV K65R 0 4 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. L10F 2020 Virology journal Table HIV L10F 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. A62V 2020 PloS one Table HIV A62V 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. A98G 2020 PloS one Table HIV A98G 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. D218E 2020 PloS one Table HIV D218E 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. D67N 2020 PloS one Table HIV D67N 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. F116Y 2020 PloS one Table HIV F116Y 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. F227L 2020 PloS one Table HIV F227L 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. F77L 2020 PloS one Table HIV F77L 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. H221Y 2020 PloS one Table HIV H221Y 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. I94L 2020 PloS one Table HIV I94L 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. K103N 2020 PloS one Table HIV K103N 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. K20T 2020 PloS one Table HIV K20T 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. K223E 2020 PloS one Table HIV K223E 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. K223R 2020 PloS one Table HIV K223R 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. L100I 2020 PloS one Table HIV L100I 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. L109I 2020 PloS one Table HIV L109I 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. L234I 2020 PloS one Table HIV L234I 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. M184V 2020 PloS one Table HIV M184V 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. M230L 2020 PloS one Table HIV M230L 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. M41L 2020 PloS one Table HIV M41L 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. N88S 2020 PloS one Table HIV N88S 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. P225H 2020 PloS one Table HIV P225H 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Q151M 2020 PloS one Table HIV Q151M 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Q58E 2020 PloS one Table HIV Q58E 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. T139K 2020 PloS one Table HIV T139K 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. V106A 2020 PloS one Table HIV V106A 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. V108I 2020 PloS one Table HIV V108I 0 5 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. V75M 2020 PloS one Table HIV V75M 0 4 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. Y115F 2020 PloS one Table HIV Y115F 0 5 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. K103N 2020 Infectious disease reports Table HIV K103N 0 5 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. K20I 2020 Infectious disease reports Table HIV K20I 0 4 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. L10I/V 2020 Infectious disease reports Table HIV L10I;L10V 0;0 6;6 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. L33F 2020 Infectious disease reports Table HIV L33F 0 4 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. Y181C 2020 Infectious disease reports Table HIV Y181C 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. A62A/V 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV A62A;A62V 0;0 6;6 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. A62V 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV A62V 0 4 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. A98A 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV A98A 0 4 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. A98G 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV A98G 0 4 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. E128E 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV E128E 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. E138E 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV E138E 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. F227C 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV F227C 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. F227F 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV F227F 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. F227F/C 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV F227C;F227F 0;0 7;7 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. G190A 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV G190A 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. H221H 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV H221H 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. H221H/Y 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV H221H;H221Y 0;0 7;7 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. H221Y 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV H221Y 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. K103N 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV K103N 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. K65K 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV K65K 0 4 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. K65R 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV K65R 0 4 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. M184I 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV M184I 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. M184V 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV M184V 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. M41L 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV M41L 0 4 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. P225H 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV P225H 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. P225P/H 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV P225H;P225P 0;0 7;7 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V106A 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V106A 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V106I 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V106I 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V106M 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V106M 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V106V 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V106V 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V108V 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V108V 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V118I 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V118I 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V179D 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V179D 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V179V/I 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V179I;V179V 0;0 7;7 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V206I 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V206I 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. V75V/I 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV V75I;V75V 0;0 6;6 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Y318F 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV Y318F 0 5 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Y318Y/F 2020 Journal of acquired immune deficiency syndromes (1999) Table HIV Y318F;Y318Y 0;0 7;7 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. N155H 2020 Frontiers in molecular biosciences Table HIV N155H 0 5 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Q148H 2020 Frontiers in molecular biosciences Table HIV Q148H 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. A62V 2020 PloS one Table HIV A62V 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. A98G 2020 PloS one Table HIV A98G 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. D67G 2020 PloS one Table HIV D67G 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. D67N 2020 PloS one Table HIV D67N 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. D67T 2020 PloS one Table HIV D67T 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. E138K 2020 PloS one Table HIV E138K 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. E138Q 2020 PloS one Table HIV E138Q 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. E44A 2020 PloS one Table HIV E44A 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. E44D 2020 PloS one Table HIV E44D 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. F227F 2020 PloS one Table HIV F227F 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. F227L 2020 PloS one Table HIV F227L 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. G190A 2020 PloS one Table HIV G190A 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. H221Y 2020 PloS one Table HIV H221Y 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. I47V 2020 PloS one Table HIV I47V 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. I54V 2020 PloS one Table HIV I54V 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K101E 2020 PloS one Table HIV K101E 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K103N 2020 PloS one Table HIV K103N 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K103S 2020 PloS one Table HIV K103S 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K20T 2020 PloS one Table HIV K20T 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K219E 2020 PloS one Table HIV K219E 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K219N 2020 PloS one Table HIV K219N 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K219Q 2020 PloS one Table HIV K219Q 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K219R 2020 PloS one Table HIV K219R 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K238T 2020 PloS one Table HIV K238T 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K65R 2020 PloS one Table HIV K65R 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K70E 2020 PloS one Table HIV K70E 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K70R 2020 PloS one Table HIV K70R 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. K70S 2020 PloS one Table HIV K70S 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. L100I 2020 PloS one Table HIV L100I 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. L10F 2020 PloS one Table HIV L10F 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. L210W 2020 PloS one Table HIV L210W 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. L24I 2020 PloS one Table HIV L24I 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. L33F 2020 PloS one Table HIV L33F 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. L74I 2020 PloS one Table HIV L74I 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. M184V 2020 PloS one Table HIV M184V 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. M230L 2020 PloS one Table HIV M230L 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. M41L 2020 PloS one Table HIV M41L 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. M46I 2020 PloS one Table HIV M46I 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. N88G 2020 PloS one Table HIV N88G 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. N88S 2020 PloS one Table HIV N88S 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. P225H 2020 PloS one Table HIV P225H 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Q58E 2020 PloS one Table HIV Q58E 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. T215F 2020 PloS one Table HIV T215F 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. T215Y 2020 PloS one Table HIV T215Y 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. T69D 2020 PloS one Table HIV T69D 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. V106M 2020 PloS one Table HIV V106M 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. V108I 2020 PloS one Table HIV V108I 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. V179D 2020 PloS one Table HIV V179D 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. V179L 2020 PloS one Table HIV V179L 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. V82A 2020 PloS one Table HIV V82A 0 4 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Y181C 2020 PloS one Table HIV Y181C 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Y188F 2020 PloS one Table HIV Y188F 0 5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Y188L 2020 PloS one Table HIV Y188L 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. E138A 2020 Retrovirology Table HIV E138A 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. G73S 2020 Retrovirology Table HIV G73S 0 4 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. H221Y 2020 Retrovirology Table HIV H221Y 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. K101E 2020 Retrovirology Table HIV K101E 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. K103N 2020 Retrovirology Table HIV K103N 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. L234I 2020 Retrovirology Table HIV L234I 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. M184V 2020 Retrovirology Table HIV M184V 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. V106A 2020 Retrovirology Table HIV V106A 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. Y115F 2020 Retrovirology Table HIV Y115F 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. Y188L 2020 Retrovirology Table HIV Y188L 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. D30N 2020 SAGE open medicine Table HIV D30N 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. D67N 2020 SAGE open medicine Table HIV D67N 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. E138A/K/Q/R 2020 SAGE open medicine Table HIV E138A;E138K;E138Q;E138R 0;0;0;0 11;11;11;11 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. E92Q 2020 SAGE open medicine Table HIV E92Q 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. G190A/S 2020 SAGE open medicine Table HIV G190A;G190S 0;0 7;7 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. G48V 2020 SAGE open medicine Table HIV G48V 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. H221Y 2020 SAGE open medicine Table HIV H221Y 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. I47V 2020 SAGE open medicine Table HIV I47V 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. I50L 2020 SAGE open medicine Table HIV I50L 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. I54L/M 2020 SAGE open medicine Table HIV I54L;I54M 0;0 6;6 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. I84V 2020 SAGE open medicine Table HIV I84V 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. K101E/P 2020 SAGE open medicine Table HIV K101E;K101P 0;0 7;7 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. K103N/S 2020 SAGE open medicine Table HIV K103N;K103S 0;0 7;7 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. K219E/Q 2020 SAGE open medicine Table HIV K219E;K219Q 0;0 7;7 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. K219E/Q/R 2020 SAGE open medicine Table HIV K219E;K219Q;K219R 0;0;0 9;9;9 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. K65R 2020 SAGE open medicine Table HIV K65R 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. K70R 2020 SAGE open medicine Table HIV K70R 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. L100I 2020 SAGE open medicine Table HIV L100I 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. L210W 2020 SAGE open medicine Table HIV L210W 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. L74V 2020 SAGE open medicine Table HIV L74V 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. L90M 2020 SAGE open medicine Table HIV L90M 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. M184I 2020 SAGE open medicine Table HIV M184I 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. M184V 2020 SAGE open medicine Table HIV M184V 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. M230L 2020 SAGE open medicine Table HIV M230L 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. M41L 2020 SAGE open medicine Table HIV M41L 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. M46I/L 2020 SAGE open medicine Table HIV M46I;M46L 0;0 6;6 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. N155H 2020 SAGE open medicine Table HIV N155H 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. N88S 2020 SAGE open medicine Table HIV N88S 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Q148H 2020 SAGE open medicine Table HIV Q148H 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Q151M 2020 SAGE open medicine Table HIV Q151M 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Q58E 2020 SAGE open medicine Table HIV Q58E 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. T215Y/F 2020 SAGE open medicine Table HIV T215F;T215Y 0;0 7;7 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. T74P 2020 SAGE open medicine Table HIV T74P 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. V106A 2020 SAGE open medicine Table HIV V106A 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. V108I 2020 SAGE open medicine Table HIV V108I 0 5 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. V32I 2020 SAGE open medicine Table HIV V32I 0 4 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. V82A/S 2020 SAGE open medicine Table HIV V82A;V82S 0;0 6;6 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Y181C/V 2020 SAGE open medicine Table HIV Y181C;Y181V 0;0 7;7 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Y188L 2020 SAGE open medicine Table HIV Y188L 0 5 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. E138A 2020 Infection and drug resistance Table HIV E138A 0 5 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. K101E 2020 Infection and drug resistance Table HIV K101E 0 5 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. K103N 2020 Infection and drug resistance Table HIV K103N 0 5 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. V106I 2020 Infection and drug resistance Table HIV V106I 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. E12K 2020 mBio Table HIV E12K 0 4 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. E138K 2020 mBio Table HIV E138K 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. G123E 2020 mBio Table HIV G123E 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. K103N 2020 mBio Table HIV K103N 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. K65R 2020 mBio Table HIV K65R 0 4 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. M184I 2020 mBio Table HIV M184I 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. M184V 2020 mBio Table HIV M184V 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. R409K 2020 mBio Table HIV R409K 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. R76K 2020 mBio Table HIV R76K 0 4 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. S373T 2020 mBio Table HIV S373T 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. S451T 2020 mBio Table HIV S451T 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. T122A 2020 mBio Table HIV T122A 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. V128del 2020 mBio Table HIV V128del 0 7 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. V370A 2020 mBio Table HIV V370A 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Y181C 2020 mBio Table HIV Y181C 0 5 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Y79F 2020 mBio Table HIV Y79F 0 4 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. E138A 2020 Medicine Table HIV E138A 0 5 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. L10F 2020 Medicine Table HIV L10F 0 4 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. M184V 2020 Medicine Table HIV M184V 0 5 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. Q58E 2020 Medicine Table HIV Q58E 0 4 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. V106I 2020 Medicine Table HIV V106I 0 5 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. V82A 2020 Medicine Table HIV V82A 0 4 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. V82Y 2020 Medicine Table HIV V82Y 0 4 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. K219E 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV K219E 0 5 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. K70R 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV K70R 0 4 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. M184I 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV M184I 0 5 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. M184V 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV M184V 0 5 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. M184V/I 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV M184I;M184V 0;0 7;7 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. M41L 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV M41L 0 4 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. T215T/F 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV T215F;T215T 0;0 7;7 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. T215Y/F 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV T215F;T215Y 0;0 7;7 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. A128T 2020 Infection and drug resistance Table HIV A128T 0 5 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. E157Q 2020 Infection and drug resistance Table HIV E157Q 0 5 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. G163R 2020 Infection and drug resistance Table HIV G163R 0 5 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. T97A 2020 Infection and drug resistance Table HIV T97A 0 4 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. E138A 2020 Infection and drug resistance Table HIV E138A 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. G163K 2020 Infection and drug resistance Table HIV G163K 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. G163R 2020 Infection and drug resistance Table HIV G163R 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. H51L/R 2020 Infection and drug resistance Table HIV H51L;H51R 0;0 6;6 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. L74V 2020 Infection and drug resistance Table HIV L74V 0 4 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. P145R 2020 Infection and drug resistance Table HIV P145R 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. S147G 2020 Infection and drug resistance Table HIV S147G 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. S153Y 2020 Infection and drug resistance Table HIV S153Y 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. S230N 2020 Infection and drug resistance Table HIV S230N 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. T97A 2020 Infection and drug resistance Table HIV T97A 0 4 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. V151I 2020 Infection and drug resistance Table HIV V151I 0 5 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. Y143H 2020 Infection and drug resistance Table HIV Y143H 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. D67E 2021 BMC infectious diseases Table HIV D67E 0 4 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. D67N 2021 BMC infectious diseases Table HIV D67N 0 4 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. F77L 2021 BMC infectious diseases Table HIV F77L 0 4 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. G190A 2021 BMC infectious diseases Table HIV G190A 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. I54M 2021 BMC infectious diseases Table HIV I54M 0 4 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. K101E 2021 BMC infectious diseases Table HIV K101E 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. K103N 2021 BMC infectious diseases Table HIV K103N 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. K219N 2021 BMC infectious diseases Table HIV K219N 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. L74I 2021 BMC infectious diseases Table HIV L74I 0 4 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. M184I 2021 BMC infectious diseases Table HIV M184I 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. M46I 2021 BMC infectious diseases Table HIV M46I 0 4 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. T215I 2021 BMC infectious diseases Table HIV T215I 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. T69D 2021 BMC infectious diseases Table HIV T69D 0 4 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. V106M 2021 BMC infectious diseases Table HIV V106M 0 5 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. Y181C 2021 BMC infectious diseases Table HIV Y181C 0 5 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. A45E 2021 The Journal of biological chemistry Table HIV A45E 0 4 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. L75G 2021 The Journal of biological chemistry Table HIV L75G 0 4 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Q63R 2021 The Journal of biological chemistry Table HIV Q63R 0 4 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. T70R 2021 The Journal of biological chemistry Table HIV T70R 0 4 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. G140S 2021 Antimicrobial agents and chemotherapy Table HIV G140S 0 5 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. Q148H 2021 Antimicrobial agents and chemotherapy Table HIV Q148H 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. A62V 2020 The Pan African medical journal Table HIV A62V 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. A98G 2020 The Pan African medical journal Table HIV A98G 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. D67N 2020 The Pan African medical journal Table HIV D67N 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. E138A 2020 The Pan African medical journal Table HIV E138A 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. F53L 2020 The Pan African medical journal Table HIV F53L 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. G190A 2020 The Pan African medical journal Table HIV G190A 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. G190S 2020 The Pan African medical journal Table HIV G190S 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. G48A 2020 The Pan African medical journal Table HIV G48A 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. G48V 2020 The Pan African medical journal Table HIV G48V 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. H221Y 2020 The Pan African medical journal Table HIV H221Y 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. I54V 2020 The Pan African medical journal Table HIV I54V 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K101E 2020 The Pan African medical journal Table HIV K101E 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K101H 2020 The Pan African medical journal Table HIV K101H 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K103N 2020 The Pan African medical journal Table HIV K103N 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K103S 2020 The Pan African medical journal Table HIV K103S 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K20T 2020 The Pan African medical journal Table HIV K20T 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K219E 2020 The Pan African medical journal Table HIV K219E 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K65R 2020 The Pan African medical journal Table HIV K65R 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K70E 2020 The Pan African medical journal Table HIV K70E 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. K70T 2020 The Pan African medical journal Table HIV K70T 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. L10F 2020 The Pan African medical journal Table HIV L10F 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. L74I 2020 The Pan African medical journal Table HIV L74I 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. L74V 2020 The Pan African medical journal Table HIV L74V 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. L89T 2020 The Pan African medical journal Table HIV L89T 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. M184I 2020 The Pan African medical journal Table HIV M184I 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. M184V 2020 The Pan African medical journal Table HIV M184V 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. M230L 2020 The Pan African medical journal Table HIV M230L 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. M41L 2020 The Pan African medical journal Table HIV M41L 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. M46I 2020 The Pan African medical journal Table HIV M46I 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. M84V 2020 The Pan African medical journal Table HIV M84V 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. P225H 2020 The Pan African medical journal Table HIV P225H 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Q58E 2020 The Pan African medical journal Table HIV Q58E 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. T215F 2020 The Pan African medical journal Table HIV T215F 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. T215Y 2020 The Pan African medical journal Table HIV T215Y 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. T69D 2020 The Pan African medical journal Table HIV T69D 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V106I 2020 The Pan African medical journal Table HIV V106I 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V108I 2020 The Pan African medical journal Table HIV V108I 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V179D 2020 The Pan African medical journal Table HIV V179D 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V179E 2020 The Pan African medical journal Table HIV V179E 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V179F 2020 The Pan African medical journal Table HIV V179F 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V65R 2020 The Pan African medical journal Table HIV V65R 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V75I 2020 The Pan African medical journal Table HIV V75I 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V82A 2020 The Pan African medical journal Table HIV V82A 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. V82S 2020 The Pan African medical journal Table HIV V82S 0 4 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Y115F 2020 The Pan African medical journal Table HIV Y115F 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Y181C 2020 The Pan African medical journal Table HIV Y181C 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Y181I 2020 The Pan African medical journal Table HIV Y181I 0 5 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Y188L 2020 The Pan African medical journal Table HIV Y188L 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. E138A 2021 Drug design, development and therapy Table HIV E138A 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. E138K 2021 Drug design, development and therapy Table HIV E138K 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. E157Q 2021 Drug design, development and therapy Table HIV E157Q 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. I54V 2021 Drug design, development and therapy Table HIV I54V 0 4 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. K70E 2021 Drug design, development and therapy Table HIV K70E 0 4 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. M184V 2021 Drug design, development and therapy Table HIV M184V 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. M46I 2021 Drug design, development and therapy Table HIV M46I 0 4 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Q58E 2021 Drug design, development and therapy Table HIV Q58E 0 4 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. T215S 2021 Drug design, development and therapy Table HIV T215S 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. V106I 2021 Drug design, development and therapy Table HIV V106I 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. V106M 2021 Drug design, development and therapy Table HIV V106M 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. V179D 2021 Drug design, development and therapy Table HIV V179D 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. V179E 2021 Drug design, development and therapy Table HIV V179E 0 5 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. M184V 2021 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. G10T 2021 Retrovirology Table HIV G10T 0 4 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. T10G 2021 Retrovirology Table HIV T10G 0 4 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. D232N 2021 BMC infectious diseases Table HIV D232N 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. E157Q 2021 BMC infectious diseases Table HIV E157Q 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. G118S 2021 BMC infectious diseases Table HIV G118S 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. G149A 2021 BMC infectious diseases Table HIV G149A 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. L74I 2021 BMC infectious diseases Table HIV L74I 0 4 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. L74M 2021 BMC infectious diseases Table HIV L74M 0 4 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. M50I 2021 BMC infectious diseases Table HIV M50I 0 4 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. N155H 2021 BMC infectious diseases Table HIV N155H 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. P145S 2021 BMC infectious diseases Table HIV P145S 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Q148H 2021 BMC infectious diseases Table HIV Q148H 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Q95K 2021 BMC infectious diseases Table HIV Q95K 0 4 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. R263K 2021 BMC infectious diseases Table HIV R263K 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. S119R 2021 BMC infectious diseases Table HIV S119R 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. T66A 2021 BMC infectious diseases Table HIV T66A 0 4 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. T97A 2021 BMC infectious diseases Table HIV T97A 0 4 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. E138E/K 2021 AIDS research and therapy Table HIV E138E;E138K 0;0 7;7 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. L74L/I 2021 AIDS research and therapy Table HIV L74I;L74L 0;0 6;6 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. M184V/I 2021 AIDS research and therapy Table HIV M184I;M184V 0;0 7;7 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. M41L 2021 AIDS research and therapy Table HIV M41L 0 4 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. T215Y 2021 AIDS research and therapy Table HIV T215Y 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. A98G 2021 Infectious diseases Table HIV A98G 0 4 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. D67G 2021 Infectious diseases Table HIV D67G 0 4 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. D67N 2021 Infectious diseases Table HIV D67N 0 4 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. E138A 2021 Infectious diseases Table HIV E138A 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. E138G 2021 Infectious diseases Table HIV E138G 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. G190A 2021 Infectious diseases Table HIV G190A 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. H221Y 2021 Infectious diseases Table HIV H221Y 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. K101E 2021 Infectious diseases Table HIV K101E 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. K103N 2021 Infectious diseases Table HIV K103N 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. K219E 2021 Infectious diseases Table HIV K219E 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. K219Q 2021 Infectious diseases Table HIV K219Q 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. K238T 2021 Infectious diseases Table HIV K238T 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. K65R 2021 Infectious diseases Table HIV K65R 0 4 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. K70R 2021 Infectious diseases Table HIV K70R 0 4 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. L100I 2021 Infectious diseases Table HIV L100I 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. M184V 2021 Infectious diseases Table HIV M184V 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. M230L 2021 Infectious diseases Table HIV M230L 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. P225H 2021 Infectious diseases Table HIV P225H 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Q151M 2021 Infectious diseases Table HIV Q151M 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. T69D 2021 Infectious diseases Table HIV T69D 0 4 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. V106M 2021 Infectious diseases Table HIV V106M 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. V108I 2021 Infectious diseases Table HIV V108I 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. V108VI 2021 Infectious diseases Table HIV V108I;V108V 0;0 6;6 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. V179E 2021 Infectious diseases Table HIV V179E 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. V179T 2021 Infectious diseases Table HIV V179T 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Y115F 2021 Infectious diseases Table HIV Y115F 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Y181C 2021 Infectious diseases Table HIV Y181C 0 5 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Y188C 2021 Infectious diseases Table HIV Y188C 0 5 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. K103N 2020 AAS open research Table HIV K103N 0 5 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. M184V 2020 AAS open research Table HIV M184V 0 5 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. V106M 2020 AAS open research Table HIV V106M 0 5 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. K65K/R 2021 BMC infectious diseases Table HIV K65K;K65R 0;0 6;6 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. K65R 2021 BMC infectious diseases Table HIV K65R 0 4 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. K70K/E,Y 2021 BMC infectious diseases Table HIV K70E;K70K 0;0 8;8 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. M184I 2021 BMC infectious diseases Table HIV M184I 0 5 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. M184M/V 2021 BMC infectious diseases Table HIV M184M;M184V 0;0 7;7 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. M184V 2021 BMC infectious diseases Table HIV M184V 0 5 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. Y115F 2021 BMC infectious diseases Table HIV Y115F 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. A98G 2021 Medicine Table HIV A98G 0 4 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. G190S 2021 Medicine Table HIV G190S 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. K219Q 2021 Medicine Table HIV K219Q 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. K65R 2021 Medicine Table HIV K65R 0 4 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. L33F 2021 Medicine Table HIV L33F 0 4 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. M46I 2021 Medicine Table HIV M46I 0 4 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. M46L 2021 Medicine Table HIV M46L 0 4 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. Q58E 2021 Medicine Table HIV Q58E 0 4 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. T215A 2021 Medicine Table HIV T215A 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. V106I 2021 Medicine Table HIV V106I 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. V179D 2021 Medicine Table HIV V179D 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. V179E 2021 Medicine Table HIV V179E 0 5 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. V82A 2021 Medicine Table HIV V82A 0 4 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. Y181C 2021 Medicine Table HIV Y181C 0 5 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. A62V 2021 Open forum infectious diseases Table HIV A62V 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. D67N 2021 Open forum infectious diseases Table HIV D67N 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. F116Y 2021 Open forum infectious diseases Table HIV F116Y 0 5 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. F77L 2021 Open forum infectious diseases Table HIV F77L 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. K65R/E 2021 Open forum infectious diseases Table HIV K65E;K65R 0;0 6;6 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. K70E 2021 Open forum infectious diseases Table HIV K70E 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. K70R 2021 Open forum infectious diseases Table HIV K70R 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. L210W 2021 Open forum infectious diseases Table HIV L210W 0 5 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. L74V 2021 Open forum infectious diseases Table HIV L74V 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. M184V/I 2021 Open forum infectious diseases Table HIV M184I;M184V 0;0 7;7 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. M41L 2021 Open forum infectious diseases Table HIV M41L 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Q151M 2021 Open forum infectious diseases Table HIV Q151M 0 5 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. V75I 2021 Open forum infectious diseases Table HIV V75I 0 4 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Y115F 2021 Open forum infectious diseases Table HIV Y115F 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. A62V 2021 Infection and drug resistance Table HIV A62V 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. A98G 2021 Infection and drug resistance Table HIV A98G 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. D67G/N 2021 Infection and drug resistance Table HIV D67G;D67N 0;0 6;6 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. E138A/G 2021 Infection and drug resistance Table HIV E138A;E138G 0;0 7;7 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. F227L 2021 Infection and drug resistance Table HIV F227L 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. F77L 2021 Infection and drug resistance Table HIV F77L 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. G190A/S 2021 Infection and drug resistance Table HIV G190A;G190S 0;0 7;7 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. H221Y 2021 Infection and drug resistance Table HIV H221Y 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K101E/H/P 2021 Infection and drug resistance Table HIV K101E;K101H;K101P 0;0;0 9;9;9 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K103N/Q 2021 Infection and drug resistance Table HIV K103N;K103Q 0;0 7;7 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K20T 2021 Infection and drug resistance Table HIV K20T 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K219E/Q 2021 Infection and drug resistance Table HIV K219E;K219Q 0;0 7;7 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K238T 2021 Infection and drug resistance Table HIV K238T 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K43T 2021 Infection and drug resistance Table HIV K43T 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K65R 2021 Infection and drug resistance Table HIV K65R 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K70E/Q/R/T 2021 Infection and drug resistance Table HIV K70E;K70Q;K70R;K70T 0;0;0;0 10;10;10;10 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. L100I 2021 Infection and drug resistance Table HIV L100I 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. L210W 2021 Infection and drug resistance Table HIV L210W 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. L234I 2021 Infection and drug resistance Table HIV L234I 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. L74I/V 2021 Infection and drug resistance Table HIV L74I;L74V 0;0 6;6 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. M184I/V 2021 Infection and drug resistance Table HIV M184I;M184V 0;0 7;7 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. M230L 2021 Infection and drug resistance Table HIV M230L 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. M41L 2021 Infection and drug resistance Table HIV M41L 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. M46I 2021 Infection and drug resistance Table HIV M46I 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. P225H 2021 Infection and drug resistance Table HIV P225H 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. T215F/I/Y 2021 Infection and drug resistance Table HIV T215F;T215I;T215Y 0;0;0 9;9;9 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. T69N 2021 Infection and drug resistance Table HIV T69N 0 4 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V106I/M 2021 Infection and drug resistance Table HIV V106I;V106M 0;0 7;7 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V108I 2021 Infection and drug resistance Table HIV V108I 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V179D/E 2021 Infection and drug resistance Table HIV V179D;V179E 0;0 7;7 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V75I/M 2021 Infection and drug resistance Table HIV V75I;V75M 0;0 6;6 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. Y115F 2021 Infection and drug resistance Table HIV Y115F 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. Y181C 2021 Infection and drug resistance Table HIV Y181C 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. Y188C/H/L 2021 Infection and drug resistance Table HIV Y188C;Y188H;Y188L 0;0;0 9;9;9 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. M184V/I 2021 Journal of acquired immune deficiency syndromes (1999) Table HIV M184I;M184V 0;0 7;7 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. A98G 2021 Frontiers in microbiology Table HIV A98G 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. D30N 2021 Frontiers in microbiology Table HIV D30N 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. E138A 2021 Frontiers in microbiology Table HIV E138A 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. E138G 2021 Frontiers in microbiology Table HIV E138G 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. E138K 2021 Frontiers in microbiology Table HIV E138K 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. F227C 2021 Frontiers in microbiology Table HIV F227C 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. G190A 2021 Frontiers in microbiology Table HIV G190A 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. G73S 2021 Frontiers in microbiology Table HIV G73S 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. H221Y 2021 Frontiers in microbiology Table HIV H221Y 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. K101E 2021 Frontiers in microbiology Table HIV K101E 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. K103N 2021 Frontiers in microbiology Table HIV K103N 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. K219Q 2021 Frontiers in microbiology Table HIV K219Q 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. K70R 2021 Frontiers in microbiology Table HIV K70R 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. L210W 2021 Frontiers in microbiology Table HIV L210W 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. L234I 2021 Frontiers in microbiology Table HIV L234I 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. L33F 2021 Frontiers in microbiology Table HIV L33F 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. M184I 2021 Frontiers in microbiology Table HIV M184I 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. M184V 2021 Frontiers in microbiology Table HIV M184V 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. M46L 2021 Frontiers in microbiology Table HIV M46L 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. N83D 2021 Frontiers in microbiology Table HIV N83D 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. N88D 2021 Frontiers in microbiology Table HIV N88D 0 4 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. V106I 2021 Frontiers in microbiology Table HIV V106I 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. V179F 2021 Frontiers in microbiology Table HIV V179F 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. V179L 2021 Frontiers in microbiology Table HIV V179L 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. Y115F 2021 Frontiers in microbiology Table HIV Y115F 0 5 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. Y181C 2021 Frontiers in microbiology Table HIV Y181C 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. A62V 2021 The Pan African medical journal Table HIV A62V 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. A98G 2021 The Pan African medical journal Table HIV A98G 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. D67N 2021 The Pan African medical journal Table HIV D67N 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. E138A 2021 The Pan African medical journal Table HIV E138A 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. F53L 2021 The Pan African medical journal Table HIV F53L 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. G190A 2021 The Pan African medical journal Table HIV G190A 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. G190S 2021 The Pan African medical journal Table HIV G190S 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. G48A 2021 The Pan African medical journal Table HIV G48A 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. G48V 2021 The Pan African medical journal Table HIV G48V 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. H221Y 2021 The Pan African medical journal Table HIV H221Y 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. I54V 2021 The Pan African medical journal Table HIV I54V 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K101E 2021 The Pan African medical journal Table HIV K101E 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K101H 2021 The Pan African medical journal Table HIV K101H 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K103N 2021 The Pan African medical journal Table HIV K103N 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K103S 2021 The Pan African medical journal Table HIV K103S 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K20T 2021 The Pan African medical journal Table HIV K20T 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K219E 2021 The Pan African medical journal Table HIV K219E 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K65R 2021 The Pan African medical journal Table HIV K65R 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K70E 2021 The Pan African medical journal Table HIV K70E 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. K70T 2021 The Pan African medical journal Table HIV K70T 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. L10F 2021 The Pan African medical journal Table HIV L10F 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. L74I 2021 The Pan African medical journal Table HIV L74I 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. L74V 2021 The Pan African medical journal Table HIV L74V 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. L89T 2021 The Pan African medical journal Table HIV L89T 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. M184I 2021 The Pan African medical journal Table HIV M184I 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. M184V 2021 The Pan African medical journal Table HIV M184V 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. M230L 2021 The Pan African medical journal Table HIV M230L 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. M41L 2021 The Pan African medical journal Table HIV M41L 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. M46I 2021 The Pan African medical journal Table HIV M46I 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. M84V 2021 The Pan African medical journal Table HIV M84V 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. P225H 2021 The Pan African medical journal Table HIV P225H 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. Q58E 2021 The Pan African medical journal Table HIV Q58E 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. T215F 2021 The Pan African medical journal Table HIV T215F 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. T215Y 2021 The Pan African medical journal Table HIV T215Y 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. T69D 2021 The Pan African medical journal Table HIV T69D 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V106I 2021 The Pan African medical journal Table HIV V106I 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V108I 2021 The Pan African medical journal Table HIV V108I 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V179D 2021 The Pan African medical journal Table HIV V179D 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V179E 2021 The Pan African medical journal Table HIV V179E 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V179F 2021 The Pan African medical journal Table HIV V179F 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V65R 2021 The Pan African medical journal Table HIV V65R 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V75I 2021 The Pan African medical journal Table HIV V75I 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V82A 2021 The Pan African medical journal Table HIV V82A 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. V82S 2021 The Pan African medical journal Table HIV V82S 0 4 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. Y115F 2021 The Pan African medical journal Table HIV Y115F 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. Y181C 2021 The Pan African medical journal Table HIV Y181C 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. Y181I 2021 The Pan African medical journal Table HIV Y181I 0 5 34584606 Correlation of HIV-1 drug resistant mutations and virologic failure. Y188L 2021 The Pan African medical journal Table HIV Y188L 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. L426M 2022 AIDS (London, England) Table HIV L426M 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. M426L 2022 AIDS (London, England) Table HIV M426L 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. M426M/L 2022 AIDS (London, England) Table HIV M426L;M426M 0;0 7;7 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. M426M/T 2022 AIDS (London, England) Table HIV M426M;M426T 0;0 7;7 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. M434T 2022 AIDS (London, England) Table HIV M434T 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. M475I 2022 AIDS (London, England) Table HIV M475I 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. N375S 2022 AIDS (London, England) Table HIV N375S 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. S375H/N 2022 AIDS (London, England) Table HIV S375H;S375N 0;0 7;7 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. S375N 2022 AIDS (London, England) Table HIV S375N 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. S375T 2022 AIDS (London, England) Table HIV S375T 0 5 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. T375S 2022 AIDS (London, England) Table HIV T375S 0 5 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. E138G 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E138G 0 5 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. F227C 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV F227C 0 5 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. F227F 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV F227F 0 5 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. V179D 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V179D 0 5 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. V189I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V189I 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. A62A 2022 Antimicrobial agents and chemotherapy Table HIV A62A 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. E138A/K 2022 Antimicrobial agents and chemotherapy Table HIV E138A;E138K 0;0 7;7 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. E138E 2022 Antimicrobial agents and chemotherapy Table HIV E138E 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. E138K 2022 Antimicrobial agents and chemotherapy Table HIV E138K 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. E157Q 2022 Antimicrobial agents and chemotherapy Table HIV E157Q 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. E92Q/V 2022 Antimicrobial agents and chemotherapy Table HIV E92Q;E92V 0;0 6;6 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. F121Y 2022 Antimicrobial agents and chemotherapy Table HIV F121Y 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G118G 2022 Antimicrobial agents and chemotherapy Table HIV G118G 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G140A/C/S 2022 Antimicrobial agents and chemotherapy Table HIV G140A;G140C;G140S 0;0;0 9;9;9 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G140S 2022 Antimicrobial agents and chemotherapy Table HIV G140S 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G163R 2022 Antimicrobial agents and chemotherapy Table HIV G163R 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G193E 2022 Antimicrobial agents and chemotherapy Table HIV G193E 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. H51H 2022 Antimicrobial agents and chemotherapy Table HIV H51H 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. H51Y 2022 Antimicrobial agents and chemotherapy Table HIV H51Y 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. K219K/E 2022 Antimicrobial agents and chemotherapy Table HIV K219E;K219K 0;0 7;7 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. K65R 2022 Antimicrobial agents and chemotherapy Table HIV K65R 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. K70E 2022 Antimicrobial agents and chemotherapy Table HIV K70E 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. L68V/I 2022 Antimicrobial agents and chemotherapy Table HIV L68I;L68V 0;0 6;6 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. L74I 2022 Antimicrobial agents and chemotherapy Table HIV L74I 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. L74L/I 2022 Antimicrobial agents and chemotherapy Table HIV L74I;L74L 0;0 6;6 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. L74M/I 2022 Antimicrobial agents and chemotherapy Table HIV L74I;L74M 0;0 6;6 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. M184I/V 2022 Antimicrobial agents and chemotherapy Table HIV M184I;M184V 0;0 7;7 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. M184V 2022 Antimicrobial agents and chemotherapy Table HIV M184V 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. N155H/S 2022 Antimicrobial agents and chemotherapy Table HIV N155H;N155S 0;0 7;7 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. P145S 2022 Antimicrobial agents and chemotherapy Table HIV P145S 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Q146P 2022 Antimicrobial agents and chemotherapy Table HIV Q146P 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Q148H/K/R 2022 Antimicrobial agents and chemotherapy Table HIV Q148H;Q148K;Q148R 0;0;0 9;9;9 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Q95K 2022 Antimicrobial agents and chemotherapy Table HIV Q95K 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. R263K 2022 Antimicrobial agents and chemotherapy Table HIV R263K 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. R263R/K 2022 Antimicrobial agents and chemotherapy Table HIV R263K;R263R 0;0 7;7 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. S147G 2022 Antimicrobial agents and chemotherapy Table HIV S147G 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. S153F/Y 2022 Antimicrobial agents and chemotherapy Table HIV S153F;S153Y 0;0 7;7 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. S230R 2022 Antimicrobial agents and chemotherapy Table HIV S230R 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. T66A/I 2022 Antimicrobial agents and chemotherapy Table HIV T66A;T66I 0;0 6;6 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. T66I 2022 Antimicrobial agents and chemotherapy Table HIV T66I 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. T66T 2022 Antimicrobial agents and chemotherapy Table HIV T66T 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. T97A 2022 Antimicrobial agents and chemotherapy Table HIV T97A 0 4 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. V151I/L 2022 Antimicrobial agents and chemotherapy Table HIV V151I;V151L 0;0 7;7 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Y115F 2022 Antimicrobial agents and chemotherapy Table HIV Y115F 0 5 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Y143C/H/R/K/S/G/A 2022 Antimicrobial agents and chemotherapy Table HIV Y143A;Y143C;Y143G;Y143H;Y143K;Y143R;Y143S 0;0;0;0;0;0;0 17;17;17;17;17;17;17 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. A49G 2022 Antimicrobial agents and chemotherapy Table HIV A49G 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. A98A 2022 Antimicrobial agents and chemotherapy Table HIV A98A 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. A98G 2022 Antimicrobial agents and chemotherapy Table HIV A98G 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. D67D/N 2022 Antimicrobial agents and chemotherapy Table HIV D67D;D67N 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. D67N 2022 Antimicrobial agents and chemotherapy Table HIV D67N 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. E138A/E 2022 Antimicrobial agents and chemotherapy Table HIV E138A;E138E 0;0 7;7 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. E138E 2022 Antimicrobial agents and chemotherapy Table HIV E138E 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. E138T 2022 Antimicrobial agents and chemotherapy Table HIV E138T 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. E157Q 2022 Antimicrobial agents and chemotherapy Table HIV E157Q 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. E92E/Q 2022 Antimicrobial agents and chemotherapy Table HIV E92E;E92Q 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. G118G/R 2022 Antimicrobial agents and chemotherapy Table HIV G118G;G118R 0;0 7;7 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. G190A 2022 Antimicrobial agents and chemotherapy Table HIV G190A 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. H221Y 2022 Antimicrobial agents and chemotherapy Table HIV H221Y 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. I50I/V 2022 Antimicrobial agents and chemotherapy Table HIV I50I;I50V 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. I50V 2022 Antimicrobial agents and chemotherapy Table HIV I50V 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. I54I/V 2022 Antimicrobial agents and chemotherapy Table HIV I54I;I54V 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. I54V 2022 Antimicrobial agents and chemotherapy Table HIV I54V 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. I84I/V 2022 Antimicrobial agents and chemotherapy Table HIV I84I;I84V 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. K103S 2022 Antimicrobial agents and chemotherapy Table HIV K103S 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. K20K 2022 Antimicrobial agents and chemotherapy Table HIV K20K 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. K20R 2022 Antimicrobial agents and chemotherapy Table HIV K20R 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. K219Q 2022 Antimicrobial agents and chemotherapy Table HIV K219Q 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. K238R 2022 Antimicrobial agents and chemotherapy Table HIV K238R 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. K70K 2022 Antimicrobial agents and chemotherapy Table HIV K70K 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. K70R 2022 Antimicrobial agents and chemotherapy Table HIV K70R 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. L10I/L 2022 Antimicrobial agents and chemotherapy Table HIV L10I;L10L 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. L33F 2022 Antimicrobial agents and chemotherapy Table HIV L33F 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. L74I 2022 Antimicrobial agents and chemotherapy Table HIV L74I 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. L74L 2022 Antimicrobial agents and chemotherapy Table HIV L74L 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. L74L/M 2022 Antimicrobial agents and chemotherapy Table HIV L74L;L74M 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. L74M 2022 Antimicrobial agents and chemotherapy Table HIV L74M 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. L74V 2022 Antimicrobial agents and chemotherapy Table HIV L74V 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. M184M 2022 Antimicrobial agents and chemotherapy Table HIV M184M 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. M184V 2022 Antimicrobial agents and chemotherapy Table HIV M184V 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. M230I/M 2022 Antimicrobial agents and chemotherapy Table HIV M230I;M230M 0;0 7;7 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. M41L 2022 Antimicrobial agents and chemotherapy Table HIV M41L 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. M46I 2022 Antimicrobial agents and chemotherapy Table HIV M46I 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. M50V 2022 Antimicrobial agents and chemotherapy Table HIV M50V 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. R263K 2022 Antimicrobial agents and chemotherapy Table HIV R263K 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. R263R 2022 Antimicrobial agents and chemotherapy Table HIV R263R 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. S147G 2022 Antimicrobial agents and chemotherapy Table HIV S147G 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. T215F 2022 Antimicrobial agents and chemotherapy Table HIV T215F 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. T215F/L 2022 Antimicrobial agents and chemotherapy Table HIV T215F;T215L 0;0 7;7 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. T215L 2022 Antimicrobial agents and chemotherapy Table HIV T215L 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. T66I 2022 Antimicrobial agents and chemotherapy Table HIV T66I 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. T69A/D 2022 Antimicrobial agents and chemotherapy Table HIV T69A;T69D 0;0 6;6 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. T69N 2022 Antimicrobial agents and chemotherapy Table HIV T69N 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. T74P 2022 Antimicrobial agents and chemotherapy Table HIV T74P 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. V106I/V 2022 Antimicrobial agents and chemotherapy Table HIV V106I;V106V 0;0 7;7 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. V151I 2022 Antimicrobial agents and chemotherapy Table HIV V151I 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. V179I 2022 Antimicrobial agents and chemotherapy Table HIV V179I 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. V201I 2022 Antimicrobial agents and chemotherapy Table HIV V201I 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. V201V 2022 Antimicrobial agents and chemotherapy Table HIV V201V 0 5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. V75A 2022 Antimicrobial agents and chemotherapy Table HIV V75A 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. V82A 2022 Antimicrobial agents and chemotherapy Table HIV V82A 0 4 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Y318F 2022 Antimicrobial agents and chemotherapy Table HIV Y318F 0 5 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. A19D 2021 Microbiology spectrum Table HIV A19D 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. D15E 2021 Microbiology spectrum Table HIV D15E 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. E18L 2021 Microbiology spectrum Table HIV E18L 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. F25L 2021 Microbiology spectrum Table HIV F25L 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. G50C 2021 Microbiology spectrum Table HIV G50C 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. N170D 2021 Microbiology spectrum Table HIV N170D 0 5 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. R267K 2021 Microbiology spectrum Table HIV R267K 0 5 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. T21A 2021 Microbiology spectrum Table HIV T21A 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Y40N 2021 Microbiology spectrum Table HIV Y40N 0 4 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. A98G 2021 Journal of the International AIDS Society Table HIV A98G 0 4 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. E138A 2021 Journal of the International AIDS Society Table HIV E138A 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. E138G 2021 Journal of the International AIDS Society Table HIV E138G 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. E138K/Q 2021 Journal of the International AIDS Society Table HIV E138K;E138Q 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. E13A 2021 Journal of the International AIDS Society Table HIV E13A 0 4 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. F227C/I 2021 Journal of the International AIDS Society Table HIV F227C;F227I 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. G190A/E 2021 Journal of the International AIDS Society Table HIV G190A;G190E 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. H221Y 2021 Journal of the International AIDS Society Table HIV H221Y 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. I132M/L 2021 Journal of the International AIDS Society Table HIV I132L;I132M 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K101E 2021 Journal of the International AIDS Society Table HIV K101E 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K101H/P 2021 Journal of the International AIDS Society Table HIV K101H;K101P 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K101R 2021 Journal of the International AIDS Society Table HIV K101R 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K103H/T 2021 Journal of the International AIDS Society Table HIV K103H;K103T 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K103N 2021 Journal of the International AIDS Society Table HIV K103N 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K103R 2021 Journal of the International AIDS Society Table HIV K103R 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K103S 2021 Journal of the International AIDS Society Table HIV K103S 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. K238T/N 2021 Journal of the International AIDS Society Table HIV K238N;K238T 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. L100I 2021 Journal of the International AIDS Society Table HIV L100I 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. L234I 2021 Journal of the International AIDS Society Table HIV L234I 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. M230I/L 2021 Journal of the International AIDS Society Table HIV M230I;M230L 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. N348I 2021 Journal of the International AIDS Society Table HIV N348I 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. P225H 2021 Journal of the International AIDS Society Table HIV P225H 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. P236L 2021 Journal of the International AIDS Society Table HIV P236L 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V106A/I 2021 Journal of the International AIDS Society Table HIV V106A;V106I 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V106M 2021 Journal of the International AIDS Society Table HIV V106M 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V108I 2021 Journal of the International AIDS Society Table HIV V108I 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V108I/V 2021 Journal of the International AIDS Society Table HIV V108I;V108V 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V109I 2021 Journal of the International AIDS Society Table HIV V109I 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V179D 2021 Journal of the International AIDS Society Table HIV V179D 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V179E/F 2021 Journal of the International AIDS Society Table HIV V179E;V179F 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V179G 2021 Journal of the International AIDS Society Table HIV V179G 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V179I 2021 Journal of the International AIDS Society Table HIV V179I 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V179I/T 2021 Journal of the International AIDS Society Table HIV V179I;V179T 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V179T 2021 Journal of the International AIDS Society Table HIV V179T 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. V90I 2021 Journal of the International AIDS Society Table HIV V90I 0 4 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Y181C 2021 Journal of the International AIDS Society Table HIV Y181C 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Y181C/I 2021 Journal of the International AIDS Society Table HIV Y181C;Y181I 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Y188C/H 2021 Journal of the International AIDS Society Table HIV Y188C;Y188H 0;0 7;7 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Y232H 2021 Journal of the International AIDS Society Table HIV Y232H 0 5 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Y318F 2021 Journal of the International AIDS Society Table HIV Y318F 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A326S 2022 Antimicrobial agents and chemotherapy Table HIV A326S 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A326T 2022 Antimicrobial agents and chemotherapy Table HIV A326T 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A340G 2022 Antimicrobial agents and chemotherapy Table HIV A340G 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A364A 2022 Antimicrobial agents and chemotherapy Table HIV A364A 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A364V 2022 Antimicrobial agents and chemotherapy Table HIV A364V 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A366A 2022 Antimicrobial agents and chemotherapy Table HIV A366A 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A374N 2022 Antimicrobial agents and chemotherapy Table HIV A374N 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A374P 2022 Antimicrobial agents and chemotherapy Table HIV A374P 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A374S 2022 Antimicrobial agents and chemotherapy Table HIV A374S 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A374T 2022 Antimicrobial agents and chemotherapy Table HIV A374T 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A374V 2022 Antimicrobial agents and chemotherapy Table HIV A374V 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. DeltaA374 2022 Antimicrobial agents and chemotherapy Table HIV DeltaA374 0 9 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. DeltaT371 2022 Antimicrobial agents and chemotherapy Table HIV DeltaT371 0 9 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. DeltaV370 2022 Antimicrobial agents and chemotherapy Table HIV DeltaV370 0 9 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. G357S 2022 Antimicrobial agents and chemotherapy Table HIV G357S 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. H358Y 2022 Antimicrobial agents and chemotherapy Table HIV H358Y 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. I333V 2022 Antimicrobial agents and chemotherapy Table HIV I333V 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. I376M 2022 Antimicrobial agents and chemotherapy Table HIV I376M 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. L363M 2022 Antimicrobial agents and chemotherapy Table HIV L363M 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. M367V 2022 Antimicrobial agents and chemotherapy Table HIV M367V 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. N372G 2022 Antimicrobial agents and chemotherapy Table HIV N372G 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. N372Q 2022 Antimicrobial agents and chemotherapy Table HIV N372Q 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. N372T 2022 Antimicrobial agents and chemotherapy Table HIV N372T 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. P289P 2022 Antimicrobial agents and chemotherapy Table HIV P289P 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. P339T 2022 Antimicrobial agents and chemotherapy Table HIV P339T 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Q369F 2022 Antimicrobial agents and chemotherapy Table HIV Q369F 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. R286K 2022 Antimicrobial agents and chemotherapy Table HIV R286K 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. R361K 2022 Antimicrobial agents and chemotherapy Table HIV R361K 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. S373H 2022 Antimicrobial agents and chemotherapy Table HIV S373H 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. S373N 2022 Antimicrobial agents and chemotherapy Table HIV S373N 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. S373Q 2022 Antimicrobial agents and chemotherapy Table HIV S373Q 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. S373T 2022 Antimicrobial agents and chemotherapy Table HIV S373T 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T332N 2022 Antimicrobial agents and chemotherapy Table HIV T332N 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T332S 2022 Antimicrobial agents and chemotherapy Table HIV T332S 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T33N 2022 Antimicrobial agents and chemotherapy Table HIV T33N 0 4 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T371Q 2022 Antimicrobial agents and chemotherapy Table HIV T371Q 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T375A 2022 Antimicrobial agents and chemotherapy Table HIV T375A 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T375N 2022 Antimicrobial agents and chemotherapy Table HIV T375N 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. T375S 2022 Antimicrobial agents and chemotherapy Table HIV T375S 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. V218A 2022 Antimicrobial agents and chemotherapy Table HIV V218A 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. V218I 2022 Antimicrobial agents and chemotherapy Table HIV V218I 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. V362I 2022 Antimicrobial agents and chemotherapy Table HIV V362I 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. V362V/I 2022 Antimicrobial agents and chemotherapy Table HIV V362I;V362V 0;0 7;7 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. V370A 2022 Antimicrobial agents and chemotherapy Table HIV V370A 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. V370I 2022 Antimicrobial agents and chemotherapy Table HIV V370I 0 5 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. V370M 2022 Antimicrobial agents and chemotherapy Table HIV V370M 0 5 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). G190A 2021 The Pan African medical journal Table HIV G190A 0 5 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). K103N 2021 The Pan African medical journal Table HIV K103N 0 5 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). K65R 2021 The Pan African medical journal Table HIV K65R 0 4 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). M184V 2021 The Pan African medical journal Table HIV M184V 0 5 34795836 Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA). Y181C 2021 The Pan African medical journal Table HIV Y181C 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. E138A/G 2021 Infection and drug resistance Table HIV E138A;E138G 0;0 7;7 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. G190A 2021 Infection and drug resistance Table HIV G190A 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. H221Y 2021 Infection and drug resistance Table HIV H221Y 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. K101E 2021 Infection and drug resistance Table HIV K101E 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. K103N 2021 Infection and drug resistance Table HIV K103N 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. K219Q 2021 Infection and drug resistance Table HIV K219Q 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. L100V 2021 Infection and drug resistance Table HIV L100V 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. M184V 2021 Infection and drug resistance Table HIV M184V 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. P225H 2021 Infection and drug resistance Table HIV P225H 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Q151M 2021 Infection and drug resistance Table HIV Q151M 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. T215F 2021 Infection and drug resistance Table HIV T215F 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. T215I 2021 Infection and drug resistance Table HIV T215I 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. T215N 2021 Infection and drug resistance Table HIV T215N 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. T215Y 2021 Infection and drug resistance Table HIV T215Y 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. V106M/A 2021 Infection and drug resistance Table HIV V106A;V106M 0;0 7;7 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. V108I 2021 Infection and drug resistance Table HIV V108I 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. V90I 2021 Infection and drug resistance Table HIV V90I 0 4 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Y115F 2021 Infection and drug resistance Table HIV Y115F 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Y181C 2021 Infection and drug resistance Table HIV Y181C 0 5 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. M50I 2021 Viruses Table HIV M50I 0 4 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. N79S 2021 Viruses Table HIV N79S 0 4 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. S17N 2021 Viruses Table HIV S17N 0 4 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. D67N 2022 AIDS (London, England) Table HIV D67N 0 4 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. E138A 2022 AIDS (London, England) Table HIV E138A 0 5 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. G190A/S 2022 AIDS (London, England) Table HIV G190A;G190S 0;0 7;7 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. K103N/S 2022 AIDS (London, England) Table HIV K103N;K103S 0;0 7;7 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. K219Q/E 2022 AIDS (London, England) Table HIV K219E;K219Q 0;0 7;7 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. K65R 2022 AIDS (London, England) Table HIV K65R 0 4 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. K70R 2022 AIDS (London, England) Table HIV K70R 0 4 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. L210W 2022 AIDS (London, England) Table HIV L210W 0 5 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. L74V 2022 AIDS (London, England) Table HIV L74V 0 4 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. L90M 2022 AIDS (London, England) Table HIV L90M 0 4 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. M184V/I 2022 AIDS (London, England) Table HIV M184I;M184V 0;0 7;7 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. M41L 2022 AIDS (London, England) Table HIV M41L 0 4 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. M46I/L 2022 AIDS (London, England) Table HIV M46I;M46L 0;0 6;6 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. T215Y/F 2022 AIDS (London, England) Table HIV T215F;T215Y 0;0 7;7 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. V108V/I 2022 AIDS (London, England) Table HIV V108I;V108V 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. A128T 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV A128T 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. D30D/N 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV D30D;D30N 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. D30N 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV D30N 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. D67N 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV D67N 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. E138A 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E138A 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. E138A/G 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E138A;E138G 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. E138K/A 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E138A;E138K 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. E157K/Q 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E157K;E157Q 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. E170A 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E170A 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. E92G 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E92G 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. E92Q/G 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV E92G;E92Q 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. F121C 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV F121C 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. F121Y 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV F121Y 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. F227C 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV F227C 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. G118R 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV G118R 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. G140A/C/S 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV G140A;G140C;G140S 0;0;0 9;9;9 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. G163K 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV G163K 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. G190A/E 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV G190A;G190E 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. G190E 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV G190E 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. G48V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV G48V 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. H221Y 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV H221Y 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. H51Y 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV H51Y 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. I47A/V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV I47A;I47V 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. I50L/V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV I50L;I50V 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. I54M/L 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV I54L;I54M 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. I84V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV I84V 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K101E/P 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K101E;K101P 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K101P/Q 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K101P;K101Q 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K103N 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K103N 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K103N/S 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K103N;K103S 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K219E/N 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K219E;K219N 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K219Q 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K219Q 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K65R/E 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K65E;K65R 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K70E 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K70E 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K70E/G 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K70E;K70G 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. K70R 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV K70R 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L100I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L100I 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L210W 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L210W 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L68V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L68V 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L68V/I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L68I;L68V 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L74I/M 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L74I;L74M 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L74M 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L74M 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L74V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L74V 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L74V/I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L74I;L74V 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L76V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L76V 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. L90M 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV L90M 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. M184V 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV M184V 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. M184V/I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV M184I;M184V 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. M230I/L 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV M230I;M230L 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. M41L 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV M41L 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. M46I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV M46I 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. M46I/L 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV M46I;M46L 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. M50I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV M50I 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. N155S 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV N155S 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. N83D 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV N83D 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. N88S 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV N88S 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. P145S 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV P145S 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. P225H 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV P225H 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Q146R/I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Q146I;Q146R 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Q148H/K/R 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Q148H;Q148K;Q148R 0;0;0 9;9;9 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Q148K 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Q148K 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Q148R 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Q148R 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Q151M 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Q151M 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Q58E 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Q58E 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Q95K/R 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Q95K;Q95R 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. R263K 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV R263K 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. S119P 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV S119P 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. S119P/R 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV S119P;S119R 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. S119R 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV S119R 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. S119T 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV S119T 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. S147G 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV S147G 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. S153A/F/Y 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV S153A;S153F;S153Y 0;0;0 9;9;9 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. T215F/Y 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV T215F;T215Y 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. T66I/A 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV T66A;T66I 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. T74P 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV T74P 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. T97A 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV T97A 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V106A 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V106A 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V108I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V108I 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V151L 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V151L 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V179L 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V179L 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V32I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V32I 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V72A/N 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V72A;V72N 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V82A 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V82A 0 4 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. V82A/F 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV V82A;V82F 0;0 6;6 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Y115F 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Y115F 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Y143C 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Y143C 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Y143H 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Y143H 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Y143R/H/C 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Y143C;Y143H;Y143R 0;0;0 9;9;9 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Y181C 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Y181C 0 5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Y181C/I 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Y181C;Y181I 0;0 7;7 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Y188C/H 2022 Journal of acquired immune deficiency syndromes (1999) Table HIV Y188C;Y188H 0;0 7;7 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. A62V 2022 PloS one Table HIV A62V 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. A98G 2022 PloS one Table HIV A98G 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. E138A 2022 PloS one Table HIV E138A 0 5 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. E40F 2022 PloS one Table HIV E40F 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. E44D 2022 PloS one Table HIV E44D 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. F77L 2022 PloS one Table HIV F77L 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. G73S 2022 PloS one Table HIV G73S 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. I85V 2022 PloS one Table HIV I85V 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. K20T 2022 PloS one Table HIV K20T 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. K238T 2022 PloS one Table HIV K238T 0 5 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. K43T 2022 PloS one Table HIV K43T 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. K65R 2022 PloS one Table HIV K65R 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. L10F 2022 PloS one Table HIV L10F 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. L210W 2022 PloS one Table HIV L210W 0 5 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. L33F 2022 PloS one Table HIV L33F 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. L89V 2022 PloS one Table HIV L89V 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. M41L 2022 PloS one Table HIV M41L 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. N83D 2022 PloS one Table HIV N83D 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. N88D 2022 PloS one Table HIV N88D 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. P225H 2022 PloS one Table HIV P225H 0 5 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. Q58E 2022 PloS one Table HIV Q58E 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. T69D 2022 PloS one Table HIV T69D 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. T74P 2022 PloS one Table HIV T74P 0 4 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. V106I 2022 PloS one Table HIV V106I 0 5 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. V108I 2022 PloS one Table HIV V108I 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. D480E 2022 Scientific reports Table HIV D480E 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. D480N 2022 Scientific reports Table HIV D480N 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. E460A 2022 Scientific reports Table HIV E460A 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. E482G 2022 Scientific reports Table HIV E482G 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. I479G 2022 Scientific reports Table HIV I479G 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. I479K 2022 Scientific reports Table HIV I479K 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. I479R 2022 Scientific reports Table HIV I479R 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. I54L 2022 Scientific reports Table HIV I54L 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. I54V 2022 Scientific reports Table HIV I54V 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. I64M 2022 Scientific reports Table HIV I64M 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. I84V 2022 Scientific reports Table HIV I84V 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. K20T 2022 Scientific reports Table HIV K20T 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. L10F 2022 Scientific reports Table HIV L10F 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. L33F 2022 Scientific reports Table HIV L33F 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. L449F 2022 Scientific reports Table HIV L449F 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. L483Q 2022 Scientific reports Table HIV L483Q 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. L89V 2022 Scientific reports Table HIV L89V 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. L90M 2022 Scientific reports Table HIV L90M 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. M46I 2022 Scientific reports Table HIV M46I 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. P453L 2022 Scientific reports Table HIV P453L 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Q474P 2022 Scientific reports Table HIV Q474P 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Q58E 2022 Scientific reports Table HIV Q58E 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. R464G 2022 Scientific reports Table HIV R464G 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. S462L 2022 Scientific reports Table HIV S462L 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. S465F 2022 Scientific reports Table HIV S465F 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. T487A 2022 Scientific reports Table HIV T487A 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. T487V 2022 Scientific reports Table HIV T487V 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. V32I 2022 Scientific reports Table HIV V32I 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. V467E 2022 Scientific reports Table HIV V467E 0 5 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. V82A 2022 Scientific reports Table HIV V82A 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. V82T 2022 Scientific reports Table HIV V82T 0 4 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Y484P 2022 Scientific reports Table HIV Y484P 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. A98G 2022 The Journal of antimicrobial chemotherapy Table HIV A98G 0 4 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. E138A 2022 The Journal of antimicrobial chemotherapy Table HIV E138A 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. G190A 2022 The Journal of antimicrobial chemotherapy Table HIV G190A 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. K101E 2022 The Journal of antimicrobial chemotherapy Table HIV K101E 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. K103N 2022 The Journal of antimicrobial chemotherapy Table HIV K103N 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. K238T 2022 The Journal of antimicrobial chemotherapy Table HIV K238T 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. K70R 2022 The Journal of antimicrobial chemotherapy Table HIV K70R 0 4 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. M184V 2022 The Journal of antimicrobial chemotherapy Table HIV M184V 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. M41L 2022 The Journal of antimicrobial chemotherapy Table HIV M41L 0 4 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. R2598L 2022 The Journal of antimicrobial chemotherapy Table HIV R2598L 0 6 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. T215Y 2022 The Journal of antimicrobial chemotherapy Table HIV T215Y 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. V108I 2022 The Journal of antimicrobial chemotherapy Table HIV V108I 0 5 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. V75M 2022 The Journal of antimicrobial chemotherapy Table HIV V75M 0 4 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. Y181C 2022 The Journal of antimicrobial chemotherapy Table HIV Y181C 0 5 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. E138A 2022 Clinical case reports Table HIV E138A 0 5 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. V179E 2022 Clinical case reports Table HIV V179E 0 5 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. A71S 2021 Virus evolution Table HIV A71S 0 4 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. A71V 2021 Virus evolution Table HIV A71V 0 4 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. L10M 2021 Virus evolution Table HIV L10M 0 4 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Q92I 2021 Virus evolution Table HIV Q92I 0 4 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Q92N 2021 Virus evolution Table HIV Q92N 0 4 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. V32C 2021 Virus evolution Table HIV V32C 0 4 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. V32I 2021 Virus evolution Table HIV V32I 0 4 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. E138A 2022 Pharmacogenomics and personalized medicine Table HIV E138A 0 5 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. E157Q 2022 Pharmacogenomics and personalized medicine Table HIV E157Q 0 5 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. G163R 2022 Pharmacogenomics and personalized medicine Table HIV G163R 0 5 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. Q95K 2022 Pharmacogenomics and personalized medicine Table HIV Q95K 0 4 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. S230R 2022 Pharmacogenomics and personalized medicine Table HIV S230R 0 5 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. T97A 2022 Pharmacogenomics and personalized medicine Table HIV T97A 0 4 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Control reactions were performed in which either no enzyme was added (C), or an RNAse H-defective mutant (E478Q) was added (RNase H-) (see Methods secion). 2005 AIDS research and therapy Figure HIV E478Q 106 111 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. Non-specific nuclease activity of I267A sIN derivatives. 2006 Retrovirology Figure HIV I267A 34 39 16956392 HIV-2 Protease resistance defined in yeast cells. 1: BY4741 [pRS316Gal1/10-HIV2PR] grown in glucose, 2: 25 ng of purified recombinant HIV-2 PR [34], 3: BY4741 [pRS316Gal1/10-HIV2PR(D25A)] grown in galactose, 4 : BY4741 [pRS316Gal1/10-HIV2PR] grown in galactose in the presence of 60 muM LPV. 2006 Retrovirology Figure HIV D25A 131 135 PR 90 92 16956392 HIV-2 Protease resistance defined in yeast cells. A) BY4741 cells transformed either with pRS316Gal1/10 (1), pRS316Gal1/10-HIV2PR (2) or pRS316Gal1/10-HIV2PR-D25A were plated on minimal selective media containing glucose and replica-plated on galactose containing media in the presence or the absence of 200 muM Saquinavir. 2006 Retrovirology Figure HIV D25A 108 112 16956392 HIV-2 Protease resistance defined in yeast cells. B) 0.25 OD600 of yeast cells transformed either with HIV-2ROD Protease (wt), or with a genetically inactivated version of HIV-2ROD Protease (D25A), were incubated in 5 ml of liquid SGalC-Ura for 60 hours. 2006 Retrovirology Figure HIV D25A 141 145 PR;PR 62;131 70;139 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. 293T cells were transfected with vectors expressing Flag-tagged WT Tat (lane 2), Tat S16A (lane 3), Tat S46A (lane 4) or Tat S16,46A (lane 5). 2006 Retrovirology Figure HIV S16A;S46A 85;104 89;108 Tat;Tat;Tat;Tat 67;81;100;121 70;84;103;124 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. A, COS-7 cells were transfected with WT Tat, Tat S16A, Tat S46A or Tat S16,46A expression vectors. 2006 Retrovirology Figure HIV S16A;S46A 49;59 53;63 Tat;Tat;Tat;Tat 40;45;55;67 43;48;58;70 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. B, HeLa cells were transfected with the HIV-1 LTR-LacZ expression vector alone (not shown here) and in combination with WT Tat, Tat S16A, Tat S46A or Tat S16,46A expression vectors. 2006 Retrovirology Figure HIV S16A;S46A 132;142 136;146 LTR;Tat;Tat;Tat;Tat 46;123;128;138;150 49;126;131;141;153 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. HLM1 cells were transfected with vectors expressing Flag-tagged Tat (WT Tat, Tat S16A, Tat S46A or Tat S16,46A). 2006 Retrovirology Figure HIV S16A;S46A 81;91 85;95 Tat;Tat;Tat;Tat;Tat 64;72;77;87;99 67;75;80;90;102 17083724 Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. Various Flag-tagged Tat (WT Tat, Tat S16A, Tat S46A or Tat S16,46A) expression vectors were used for HLM-1 transfections. 2006 Retrovirology Figure HIV S16A;S46A 37;47 41;51 Tat;Tat;Tat;Tat;Tat 20;28;33;43;55 23;31;36;46;58 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. HIV-2[Env42S] and HIV-2/I73V[Env42] viruses were used to infect TZM-LNCX2 cells (closed symbols) and TZM-huTRIM5alphacells (open symbols). 2006 Retrovirology Figure HIV I73V 24 28 Env;Env 6;29 9;32 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. HIV-2[VSV-G] and HIV-2/I73V[VSV-G] viruses were used to infect TZM-LNCX2 cells (closed symbols) and TZM-huTRIM5alpha cells (open symbols). 2006 Retrovirology Figure HIV I73V 23 27 17087820 Human TRIM5alpha mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants. The capsid mutation at position 73 (I73V) confers escape from Lv2-mediated restriction on TZM-LNCX2 cells (9.3 fold increase in infection), whereas the over expression of human TRIM5alpha in TZM-huTRIM5alpha cells results in a maximal restriction for both virus variants. 2006 Retrovirology Figure HIV I73V 36 40 Capsid 4 10 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Cell-cell fusion assay with the GIA-SKY mutant and the GIA-SKY-G431R revertant. 2006 Retrovirology Figure HIV G431R 63 68 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Closed circles represent the original GIA-SKY mutant virus and open circles the GIA-SKY-G431R revertant. 2006 Retrovirology Figure HIV G431R 88 93 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Position 431 variation in the GIA-SKY T20-dependent virus (top) and the wild-type GIV-SNY virus (bottom): wild-type 431G (closed circles), G431R (open circles), G431E (dashes) and G431A (open triangles, in wild-type only). 2006 Retrovirology Figure HIV G431A;G431E;G431R 180;161;139 185;166;144 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Replication of the T20-dependent GIA-SKY mutant and the GIA-SKY-G431R revertant virus. 2006 Retrovirology Figure HIV G431R 64 69 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. Sensitivity of wild-type GIV-SNY and GIA-SKY-G431R revertant viruses to sCD4 and D5-IgG1 gp41 antibody. 2006 Retrovirology Figure HIV G431R 45 50 gp41 89 93 17134507 Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. The G431R change that was selected in multiple cultures is marked in bold. 2006 Retrovirology Figure HIV G431R 4 9 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. (C) Western blotting of nuclear extracts isolated from Cos7 cells cotransfected with RSK2/HA and Tat/FLAG or with RSK2/HA and Tat F38A/FLAG constructs. 2007 PloS one Figure HIV F38A 130 134 Tat;Tat 97;126 100;129 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. (B) Many particles produced by cells transfected with the E98A mutant had either virions with an immature structure or abnormal core morphology (left panel) and a very few detectable cones. 2007 Retrovirology Figure HIV E98A 58 62 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. (C) E187G virions with a characteristic dense conical core material. 2007 Retrovirology Figure HIV E187G 2 9 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. (C) TZM-bl cells (8 x 104) were infected as described above with 400 ng of wild-type NL4-3 virus or with E98A virus that was first immunoprecipitated with anti-Tat monoclonal antibody (indicated with IP 400). 2007 Retrovirology Figure HIV E98A 105 109 Tat 160 163 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Cells were also infected with E98A virus stock that had been two-fold serially diluted. 2007 Retrovirology Figure HIV E98A 30 34 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Equal amounts of total RNA isolated from E98A infected TZM-bl cells were subjected to nested RT-PCR using specific primers that amplified a 593 bp fragment of the p17 viral RNA. 2007 Retrovirology Figure HIV E98A 41 45 RT 93 95 17371591 Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity. Under higher magnification, the E98A virions were observed to be a heterogeneous population of particles (right panel) with varying size and conical core structures, where a number of virions with an electron-lucent centre and aberrant cores were detected (lower panel). 2007 Retrovirology Figure HIV E98A 32 36 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. (B and C) MT-4 p75- and MT-4 mut cells were infected at an MOI of 0.5 (B) or 2.5 (C) with the following viral clones: WT NL4.3 (diamonds) or NL4.3 A128T/E170G (crosses). 2007 PLoS pathogens Figure HIV E170G;A128T 153;147 158;152 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. (B) PBLs were inoculated with WT or mutant viral clones at an MOI of 0.01: WT NL4.3 (diamonds), NL4.3 A128T (boxes), NL4.3 E170G (triangles), or NL4.3 A128T/E170G (crosses). 2007 PLoS pathogens Figure HIV E170G;A128T 157;151 162;156 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. (D) Jurkat cells encoding a shRNA directed against LEDGF/p75 (Jurkat p75- cells) and BC Jurkat cells were infected at an MOI of 0.5 with WT NL4.3 (diamonds) or NL4.3 A128T/E170G (crosses). 2007 PLoS pathogens Figure HIV E170G;A128T 172;166 177;171 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. HeLaP4 eGFP-Delta325 or HeLaP4 cells overexpressing eGFP-LEDGF/p75(K150A) in the cytoplasm were transfected with plasmids encoding WT or double mutant A128T/E170G mRFP-INs. 2007 PLoS pathogens Figure HIV A128T;E170G;K150A 151;157;67 156;162;72 IN 168 171 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Interaction between eGFP-Delta325 or eGFP-LEDGF/p75(K150A) with WT mRFP-INs or A128T/E170G mRFP-INs was detected by measuring the simultaneous diffusion of the differentially labeled proteins using FCCS. 2007 PLoS pathogens Figure HIV A128T;E170G;K150A 79;85;52 84;90;57 IN;IN 72;96 75;99 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. MT-4 eGFP-Delta325 (A) and MT-4 eGFP-Delta325 D366A cells (B) were infected at an MOI of 0.5 with the following viral clones: WT NL4.3 (diamonds), NL4.3 A128T (boxes), NL4.3 E170G (triangles), or NL4.3 A128T/E170G (crosses). 2007 PLoS pathogens Figure HIV E170G;A128T 208;202 213;207 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The enzymatic activity was determined by measuring strand transfer products for the single mutants IN-A128T and IN-E170G and the double mutant IN-A128T/E170G in comparison with WT-IN. 2007 PLoS pathogens Figure HIV A128T;A128T;E170G;E170G 102;146;115;152 107;151;120;157 IN;IN;IN;IN 99;112;143;180 101;114;145;182 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. After a ~6 log increase in viremia (consisting of K65R virus), virus levels decreased rapidly (with estimated half-life of productively infected cells of 0.9 days) as soon as CD8+ cells started to return. 2007 Retrovirology Figure HIV K65R 50 54 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. At the onset of tenofovir therapy (i.e, baseline, BL), no K65R and K70E virus could be detected. 2007 Retrovirology Figure HIV K65R;K70E 58;67 62;71 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Despite an initial rebound associated with emergence of K70E followed by K65R viral mutants (table 1. 2007 Retrovirology Figure HIV K65R;K70E 73;56 77;60 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Kinetics of K70E and K65R RT mutants during tenofovir therapy. 2007 Retrovirology Figure HIV K65R;K70E 21;12 25;16 RT 26 28 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Plasma viral RNA samples in which real-time PCR assays detected both K65R and K70E mutations were analyzed further; representative samples are shown. 2007 Retrovirology Figure HIV K65R;K70E 69;78 73;82 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Real-time PCR technology was used to quantitate K65R and K70E RT mutants in plasma samples; values are expressed as percentage of total viral RNA copy number. 2007 Retrovirology Figure HIV K65R;K70E 48;57 52;61 RT 62 64 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Segregation of K65R and K70E mutations, and linkage of codon 68 mutations with K65R. 2007 Retrovirology Figure HIV K65R;K65R;K70E 15;79;24 19;83;28 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The earliest detection of the K70E or K65R mutation in viral RNA in plasma virus by real-time RT-PCR is indicated (see Figure 6 for more details). 2007 Retrovirology Figure HIV K65R;K70E 38;30 42;34 RT 94 96 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The mutation-specific amplicons from this specimen also exhibited segregation of K65R and K70E. 2007 Retrovirology Figure HIV K65R;K70E 81;90 85;94 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The red and blue circles indicate the first detection of K70E and K65R, respectively; weeks indicate weeks of tenofovir treatment. 2007 Retrovirology Figure HIV K65R;K70E 66;57 70;61 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Thus, the K65R and K70E mutations were on separate viral genomes. 2007 Retrovirology Figure HIV K65R;K70E 10;19 14;23 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Includes the 22 mutations obtained from the mutation pairs with the highest positive association (Table 1) in bold, and 13 additional clinically relevant protease inhibitor resistance mutations (L10F, V32I, L33F, I47V, I50V/L, F53L, I54L/M, Q58E, L76V, V82T, and N88S). 2007 PLoS computational biology Figure HIV F53L;I47V;I50L;I50V;I54L;I54M;L10F;L33F;L76V;N88S;Q58E;V32I;V82T 227;213;219;219;233;233;195;207;247;263;241;201;253 231;217;225;225;239;239;199;211;251;267;245;205;257 PR 154 162 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Includes the 23 mutations obtained from the mutation pairs with highest positive association (Table 2) in bold, and 11 additional clinically relevant nucleoside RT inhibitor resistance mutations (K65R, A62V, T69ins, L74I/V, V75M, Y115F, M184V, and K219R/E/N). 2007 PLoS computational biology Figure HIV A62V;K219E;K219N;K219R;K65R;L74I;L74V;M184V;T69ins;V75M;Y115F 202;248;248;248;196;216;216;237;208;224;230 206;257;257;257;200;222;222;242;214;228;235 RT 161 163 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Flag-DCAF1 was cotransfected into HeLa cells with either HA-Vpr or HA-Vpr(R80A). 2007 Virology journal Figure HIV R80A 74 78 Vpr;Vpr 60;70 63;73 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. GFP, HA-Vpr, HA-Vpr(R80A), or HA-Vpr(Q65R) constructs were transfected, and immunoprecipitations with HA antibody were performed. 2007 Virology journal Figure HIV Q65R;R80A 37;20 41;24 Vpr;Vpr;Vpr 8;16;33 11;19;36 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. HA-Vpr(Q65R) fails to interact with DCAF1. 2007 Virology journal Figure HIV Q65R 7 11 Vpr 3 6 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. HeLa cells were infected with a constant MOI (MOI = 1) of pHR-VPR vector, and a variable MOI (1, 0.5, 0.25) of pHR-GFP, pHR- Vpr(R80A) or pHR-VPR(Q65R, R80A) as indicated. 2007 Virology journal Figure HIV Q65R;R80A;R80A 146;129;152 150;133;156 Vpr;Vpr;Vpr 62;125;142 65;128;145 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Incubation with epoxomicin or overexpression of Ub(K48R) block Vpr induced G2 arrest when induced by Vpr, but not when induced by the topoisomerase inhibitor, etoposide. 2007 Virology journal Figure HIV K48R 51 55 Vpr;Vpr 63;101 66;104 17559673 HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Vpr(R80A) functions as a dominant-negative molecule. 2007 Virology journal Figure HIV R80A 4 8 Vpr 0 3 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Additionally, a large pool of virus-like structures inside vesicles released from transfected cells were observed in D51N mutant. 2007 Retrovirology Figure HIV D51N 117 121 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Green, D51E; red, D51Q; blue, wild type; pink, D51N. 2007 Retrovirology Figure HIV D51E;D51N;D51Q 7;47;18 11;51;22 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Micrographs of the CAp24 mutant D51N (A), D51E (B), D51Q (C) and the wild type CAp24 (D). 2007 Retrovirology Figure HIV D51E;D51N;D51Q 42;32;52 46;36;56 Capsid;Capsid 19;79 21;81 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Mutants D51N and D51Q showed mostly heterogenous populations of particles with varying size and morphology (panels D51Q and inset in panel D51N). 2007 Retrovirology Figure HIV D51N;D51N;D51Q;D51Q 8;139;17;115 12;143;21;119 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. NT, a mock control; WT, wild type; and D51N, D51E, and D51Q are the three CAp24 mutants. 2007 Retrovirology Figure HIV D51E;D51N;D51Q 45;39;55 49;43;59 Capsid 74 76 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Occasionally, D51E virions resembling the mature wild type morphology but with aberrant core structure was also observed. 2007 Retrovirology Figure HIV D51E 14 18 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. With the wild type and D51E virions particles representing immature-like viruses are shown (panels D51E and WT). 2007 Retrovirology Figure HIV D51E;D51E 23;99 27;103 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. (B and C) Histograms indicating the surface expression of co-stimulatory molecules or DC maturation markers after exposure of ILT4 or ILT2 siRNA-transfected myelomonocytic cells to HLA-B2705-KK10 WT or L6M pentamers (B) or to autologous HLA-B2705-expressing DCs pulsed with the KK10 WT or KK10 L6M variant peptide (C). 2007 The Journal of experimental medicine Figure HIV L6M 202 205 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. (C) Mean and standard deviation of the fluorescence intensity of DC maturation markers and co-stimulatory molecules after cytokine cocktail-mediated maturation in the presence or absence of the B2705-KK10 WT or L6M pentamers. 2007 The Journal of experimental medicine Figure HIV L6M 211 214 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. (C) Mean fluorescence intensity of the B2705-KK10 WT and L6M variant pentamers after staining with the indicated pentamer dilutions (x axis) on CD14+ macrophages. 2007 The Journal of experimental medicine Figure HIV L6M 57 60 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. Dot plots indicate the proportion of allogenic CD4 or CD8 T cells after a 6-d exposure to MDDCs in the presence of HLA-B27-KK10 WT or L6M pentamers. 2007 The Journal of experimental medicine Figure HIV L6M 134 137 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. B and C) The L23F or K27M mutations were introduced into the vpr gene of the HIV-1YU-2 molecular clone. 2007 Retrovirology Figure HIV K27M;L23F 21;13 25;17 Vpr 61 64 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Impact of the Vpr-L23F and -K27M substitutions on the three-dimensional structure of Vpr. 2007 Retrovirology Figure HIV K27M;L23F 28;18 32;22 Vpr;Vpr 14;85 17;88 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. The L40 yeast reporter strain expressing the wt or mutated (clones 11 and 35, and Vpr-R90K and -W54R single-point mutants) HIV-1 Vpr fused either to LexABD (upper panels) or to the Gal4 DNA binding domain (Gal4BD) (lower panels), in combination with each of the Gal4AD-hybrids indicated on the top was analyzed for histidine auxotrophy and beta-Gal activity. 2007 Retrovirology Figure HIV R90K;W54R 86;96 90;100 Vpr;Vpr 82;129 85;132 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. The wild type HIV-1YU-2 (WT, open diamonds) and the vpr-defective (DeltaVpr, open squares), Vpr-L23F (black circles) and -K27M (black triangles) mutant viruses were produced by transfection of 293T cells with proviral DNAs. 2007 Retrovirology Figure HIV K27M;L23F 122;96 126;100 Vpr;Vpr 52;92 55;95 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Bevirimat-resistant SP1/A1V replicates and depletes thymocytes with kinetics comparable to wild-type NL4-3 in SCID-hu Thy/Liv mice. 2007 PloS one Figure HIV A1V 24 27 SP1 20 23 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. In Vivo Competitions Reveal No Impairment of SP1/A1V Replication. 2007 PloS one Figure HIV A1V 49 52 SP1 45 48 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. NL4-3 PRI54V+V82A is hypersensitive to bevirimat in PHA-activated PBMCs with 50% inhibitory concentration (IC50) >100 times lower than for wild-type NL4-3. 2007 PloS one Figure HIV V82A 13 17 PR 6 8 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Sequencing of CA-SP1 RNA from three SCID-hu Thy/Liv mice coinfected with equivalent infectious units of NL4-3 and SP1/A1V reveal no impairment of SP1/A1V replication 28 days after implant inoculation. 2007 PloS one Figure HIV A1V;A1V 118;150 121;153 SP1;SP1;SP1;Capsid 17;114;146;14 20;117;149;16 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The A-to-V substitution in SP1 is conferred by a C-to-T mutation at nucleotide 1880. 2007 PloS one Figure HIV C1880T 49 83 SP1 27 30 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The A1V Mutation in SP1 Does Not Affect Kinetics of Viral Replication or Thymocyte Depletion. 2007 PloS one Figure HIV A1V 4 7 SP1 20 23 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The number in each graph is the proportion of SP1/A1V to NL4-3 in area under the curve. 2007 PloS one Figure HIV A1V 50 53 SP1 46 49 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. The protease mutant is deficient in CA-SP1 cleavage and is comparable to bevirimat-treated wild-type virus, however, the drug has a more dramatic effect on CA-SP1 cleavage in HIV-1 PRI54V+V82A. 2007 PloS one Figure HIV V82A 188 192 PR;SP1;SP1;Capsid;Capsid;PR 4;39;159;36;156;181 12;42;162;38;158;183 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. There was no reduction in viral load in bevirimat-treated mice inoculated with bevirimat-resistant SP1/A1V, whereas 3TC treatment (30 mg/kg per day by twice-daily oral gavage) was highly effective. 2007 PloS one Figure HIV A1V 103 106 SP1 99 102 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Thymocytes dispersed from NL4-3- and SP1/A1V-infected SCID-hu Thy/Liv implants were cultured in the presence of the indicated range of concentrations of bevirimat for 2 days. 2007 PloS one Figure HIV A1V 41 44 SP1 37 40 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Wild-type NL4-3 and protease mutant NL4-3 PRI54V+V82A virions were collected from transfected 293T cells grown in the presence (20 microM) or absence of bevirimat and analyzed for particle maturation by Western blot using a p24 monoclonal antibody. 2007 PloS one Figure HIV V82A 49 53 PR;p24;PR 20;224;42 28;227;44 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. For both (A) and (B), lanes demarcated as 1-4 included control reactions for the WT, N348I, 3AZT, and 3AZT + N348I RTs where all substituents were added except ATP. 2007 PLoS medicine Figure HIV N348I;N348I 85;109 90;114 RT 115 118 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. If subsequent time points also contained N348I, then the key mutations present at this time point was also included in the analysis. 2007 PLoS medicine Figure HIV N348I 41 46 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Isotherms for ATP-Mediated Phosphorolytic Excision of AZT-MP by WT, 3AZT, N348I, and 3AZT + N348I. 2007 PLoS medicine Figure HIV N348I;N348I 92;74 97;79 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Pattern of Emergence of N348I Early in Drug Therapy Failure. 2007 PLoS medicine Figure HIV N348I 24 29 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The last on therapy sample from a total of 3,569 patients was analysed where 3,408 and 161 samples did not or did contain N348I, respectively. 2007 PLoS medicine Figure HIV N348I 122 127 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The pattern of emergence of N348I relative to key drug resistance mutations in the RT is shown with respect to days post therapy. 2007 PLoS medicine Figure HIV N348I 28 33 RT 83 85 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The presence of the indicated key mutations was included from data available from each time point up to the appearance of N348I. 2007 PLoS medicine Figure HIV N348I 122 127 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The prevalence of key drug resistance mutations without N348I (red bars) compared to their prevalence with N348I (blue bars). 2007 PLoS medicine Figure HIV N348I;N348I 56;107 61;112 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. These patients had neither N348I nor key drug resistance mutations present at baseline. 2007 PLoS medicine Figure HIV N348I 27 32 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. Comparison of titers produced by PR expression plasmids: wt versus T26S mutant. 2007 Retrovirology Figure HIV T26S 67 71 PR 33 35 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. In addition, the active site of PR was changed from DTG to DSG to create the T26S mutant PR. 2007 Retrovirology Figure HIV T26S 77 81 PR;PR 32;89 34;91 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. In this study, the lentiviral vector (wt-LTR expressing GFP), Rev, Tat, VSV-G, Gag (non-optimized), and Vpr-RT/IN DNA amounts remained constant, while the DNA amounts of Vpr-wt PR (wt protease, shown in blue) and Vpr-T26S PR (mutant protease, shown in red) varied. 2007 Retrovirology Figure HIV T26S 217 221 PR;PR;Rev;LTR;Vpr;Vpr;Vpr;Tat;Gag;IN;PR;PR;RT 184;233;62;41;104;170;213;67;79;111;177;222;108 192;241;65;44;107;173;216;70;82;113;179;224;110 18163907 Design of a trans protease lentiviral packaging system that produces high titer virus. NIH 3T3 cells were infected with serial dilutions of viral supernatants produced by the 7 plasmid system with either the wt (blue) or T26S mutant (red) PR. 2007 Retrovirology Figure HIV T26S 134 138 PR 152 154 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Alignment of AK90m primer with mutant L90M and wild-type L90 region of protease gene (subtype B consensus). 2008 Retrovirology Figure HIV L90M 38 42 PR 71 79 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Design and test of the L90M allele-specific PCR protocol. 2008 Retrovirology Figure HIV L90M 23 27 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Labels on the tips first show the sampling date in month and year and whether the generic (P for population) or L90M specific (M for mutant) PCR primers were used to generate the sequenced amplicons. 2008 Retrovirology Figure HIV L90M 112 116 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Patients with sequences showing evidence for multiple origins of L90M are shown in red, those with a single L90M origin in blue and those with an inconclusive number of L90M origins in black. 2008 Retrovirology Figure HIV L90M;L90M;L90M 65;108;169 69;112;173 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. PCR amplification using L90M specific primer of serial log dilutions of L90 (AKp136) and L90M (AKp140) plasmid derived generic gag-pro amplicons. 2008 Retrovirology Figure HIV L90M;L90M 24;89 28;93 Gag 127 130 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Posterior support values for the monophyletic relationships of the sequences with the L90M mutation are given in Table 1. 2008 Retrovirology Figure HIV L90M 86 90 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Ratio of L90M to L90 amplicons DNA is shown. 2008 Retrovirology Figure HIV L90M 9 13 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Sensitivity of L90M allele specific PCR using serial dilution of AKp140 derived amplicon in a constant amount of AKp136 derived L90 amplicon. 2008 Retrovirology Figure HIV L90M 15 19 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Sequences that have the L90M mutation are indicated in darker bold fonts. 2008 Retrovirology Figure HIV L90M 24 28 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. A: M41L+T215Y versus M41L+T215Y+E40F B: Pat A (E40F, M41L, K43E, M184V, L210W, T215Y and K219T) versus Pat A-WT40 (M41L, K43E, M184V, L210W, T215Y and K219T). 2008 Retrovirology Figure HIV E40F;E40F;K219T;K219T;K43E;K43E;L210W;L210W;M184V;M184V;M41L;M41L;M41L;M41L;T215Y;T215Y;T215Y;T215Y 32;47;89;151;59;121;72;134;65;127;3;21;53;115;8;26;79;141 36;51;94;156;63;125;77;139;70;132;7;25;57;119;13;31;84;146 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. A: Pat A (E40F, M41L, K43E, M184V, L210W, T215Y and K219T) versus Pat A-WT43 (E40F, M41L, M184V, L210W, T215Y and K219T). 2008 Retrovirology Figure HIV E40F;E40F;K219T;K219T;K43E;L210W;L210W;M184V;M184V;M41L;M41L;T215Y;T215Y 10;78;52;114;22;35;97;28;90;16;84;42;104 14;82;57;119;26;40;102;33;95;20;88;47;109 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. B: wild type versus wild type+K43E. 2008 Retrovirology Figure HIV K43E 30 34 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. C: M41L+T215Y versus M41L+T215Y+K43E. 2008 Retrovirology Figure HIV K43E;M41L;M41L;T215Y;T215Y 32;3;21;8;26 36;7;25;13;31 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. D: M41L+T215Y+E40F versus M41L+T215Y+E40F+K43E. 2008 Retrovirology Figure HIV E40F;E40F;K43E;M41L;M41L;T215Y;T215Y 14;37;42;3;26;8;31 18;41;46;7;30;13;36 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Replication competition experiments with E40F site-directed mutants. 2008 Retrovirology Figure HIV E40F 41 45 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Replication competition experiments with K43E site-directed mutants. 2008 Retrovirology Figure HIV K43E 41 45 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. **, the accumulation of the transiently formed hybrid with the TAMs/A360V/N348I RT. 2008 The Journal of biological chemistry Figure HIV A360V;N348I 68;74 73;79 RT 80 82 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Accumulation of transiently formed hybrids with the TAMs RT containing connection domain mutations A360V and N348I. 2008 The Journal of biological chemistry Figure HIV A360V;N348I 99;109 104;114 RT 57 59 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. B, the DNA RNA substrate was incubated with the RT enzyme (WT, TAMs, TAMs/A360V, TAMs/N348I, and TAMs/A360V/N348I, respectively). 2008 The Journal of biological chemistry Figure HIV A360V;N348I;A360V;N348I 102;108;74;86 107;113;79;91 RT 48 50 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. B, the gel-based excision assay was quantified, and the amount of ATP-mediated rescue product was plotted with respect to time with WT RT , TAMs RT , and TAMs/A360V/N348I RT . 2008 The Journal of biological chemistry Figure HIV A360V;N348I 159;165 164;170 RT;RT;RT 135;145;171 137;147;173 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. DNA synthesis and ATP-mediated AZT-MP excision were monitored with enzymes containing the E478Q mutation (TAMs, TAMs/E478Q, TAMs/A360V/N348I, and TAMs/A360V/N348I/E478Q, respectively). 2008 The Journal of biological chemistry Figure HIV A360V;A360V;E478Q;N348I;N348I;E478Q;E478Q 129;151;163;135;157;90;117 134;156;168;140;162;95;122 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. DNA synthesis rescue was monitored over time in the presence of AZT and PPi for each of the RT enzymes (WT, TAMs, TAMs/A360V, TAMs/N348I, and TAMs/A360V/N348I, respectively) up to 3 h at 37 C (time points indicated). 2008 The Journal of biological chemistry Figure HIV A360V;N348I;A360V;N348I 147;153;119;131 152;158;124;136 RT 92 94 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. In step 1, mutations N348I, A360V, and TAMs promote the dissociation of the RNase H-competent complex (DNA RNA RT(RNase H)) from the nucleic acid substrate. 2008 The Journal of biological chemistry Figure HIV A360V;N348I 28;21 33;26 RT 111 113 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Proposed mechanisms for contributions of A360V and N348I to increases in excision and rescue of AZT-terminated DNA synthesis. 2008 The Journal of biological chemistry Figure HIV A360V;N348I 41;51 46;56 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. TAMs RT shows a deficit in binding the substrate in this mode, whereas TAMs/A360V facilitates binding. 2008 The Journal of biological chemistry Figure HIV A360V 76 81 RT 5 7 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The long DNA RNA (PBS-28/PBS-250) substrate was employed to assess DNA synthesis rescue over time in the presence of AZT-MP and ATP for each of the RT enzymes (WT, TAMs, TAMs/A360V, TAMs/N348I, and TAMs/A360V/N348I, respectively). 2008 The Journal of biological chemistry Figure HIV A360V;N348I;A360V;N348I 203;209;175;187 208;214;180;192 RT 148 150 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. (A) Virus particles produced from 293T cells transfected with WT, S109A, S149A or S178A molecular clones were processed as described in "Materials and Methods" and imaged in thin-layer electron microscopy. 2008 Retrovirology Figure HIV S109A;S149A;S178A 66;73;82 71;78;87 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. (B) MAGIC-5B cells were infected with normalized amounts of DNAse-treated WT, S109A, S149A or S178A viruses. 2008 Retrovirology Figure HIV S109A;S149A;S178A 78;85;94 83;90;99 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Cos7 cells incubated with increasing amounts of VSV-G pseudotyped WT or S109A, S149A or S178A-mutated virions were challenged with fixed infectious doses of HIV-1R7-GFP indicator virus. 2008 Retrovirology Figure HIV S109A;S149A;S178A 72;79;88 77;84;93 18684096 Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. Panel D: Portion of late-infected infants with NVP resistance mutations (K103N, Y181C, or G190A) detected by the LigAmp assay at the time of HIV diagnosis. 2008 The Journal of infectious diseases Figure HIV G190A;K103N;Y181C 90;73;80 95;78;85 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. 3'-P for the F121Y mutant HIV-1 integrase. 2008 Biochemistry Figure HIV F121Y 13 18 IN 32 41 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. C Defective 3'-P of the Q148K mutant shown as densitometry analysis of the gel presented in panel B (lanes 1, 4 and 7). 2008 Biochemistry Figure HIV Q148K 24 29 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Deferential effect of the E92Q integrase mutation on inhibition of 3'-processing vs. 2008 Biochemistry Figure HIV E92Q 26 30 IN 31 40 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Gel image of the inhibition of HIV-1 integrase E92Q by raltegravir using both protocols. 2008 Biochemistry Figure HIV E92Q 47 51 IN 37 46 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Gel image of typical 3'-P and ST reactions using three different concentrations of Q148K, and showing defective ST and 3'-P activities of the Q148K mutant HIV-1 integrase. 2008 Biochemistry Figure HIV Q148K;Q148K 83;142 88;147 IN 161 170 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. (A) MCC cells stably-transduced with retroviral vectors encoding full-length fCD134 (Feline), CRD1 of fCD134 in the context of hCD134 (CRD1), human CD134 (Human) or vector only control (CON) were incubated with Fc-SU fusion proteins derived from GL8 WT or glycosylation site mutants T271I and N342Y and bound protein detected using PE-anti-human IgG Fc by flow cytometry. 2008 Retrovirology Figure HIV N342Y;T271I 293;283 298;288 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. 10-20% gradient gel analysis of GL8 WT (1), T271 (2), N342Y (3) and Delta2N (4) probed with anti-FIV (subtype-specific) SU monoclonal antibody vpg71.2. 2008 Retrovirology Figure HIV N342Y 54 59 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Cells were transfected with eukaryotic expression vectors bearing the GL8 or CPG41 envs carrying the WT, T271I, N342Y or Delta2N sequences. 2008 Retrovirology Figure HIV N342Y;T271I 112;105 117;110 Env 83 87 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. HIV (FIV) pseudotypes bearing the WT, T271, N342Y or Delta2N Envs were incubated with 1/100, 1/1000 or 1/10,000 dilutions of plasma from 8 GL8-infected cats (Q251-258), or a no plasma negative control (neg), and plated onto CLL-CD134 cells. 2008 Retrovirology Figure HIV N342Y 44 49 Env 61 65 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Infection of both cell lines expressing CRD1 was enhanced significantly in the T271I and Delta2N Envs. 2008 Retrovirology Figure HIV T271I 79 84 Env 97 101 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Infection of MYA-1 and CLL-CD134 cells with HIV (FIV) pseudotypes bearing WT, T271I or N342Y mutant GL8 and CPG41 Envs was quantified in the presence of increasing concentrations of CXCR4 antagonist AMD3100. 2008 Retrovirology Figure HIV N342Y;T271I 87;78 92;83 Env 114 118 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Mutant proviral clones bearing T271I or N342Y yield infectious virus. 2008 Retrovirology Figure HIV N342Y;T271I 40;31 45;36 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Pelleted virus from MYA-1 cells infected with GL8 (1-4) and CPG41 (5-8) viruses bearing WT (1,5), T271I (2,6), N342Y (3,7) or Delta2N (4,8) were separated by reducing SDS-PAGE on a 12% acrylamide gel, transferred to nitrocellulose and probed with pooled cat anti-FIV. 2008 Retrovirology Figure HIV N342Y;T271I 111;98 116;103 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Schematic structural model of the FIV SU proteins illustrating the locations of the T271I and N342Y mutations (red), conserved cysteine residues (green) and predicted sites for N-linked glycosylation . 2008 Retrovirology Figure HIV N342Y;T271I 94;84 99;89 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Sensitivity of GL8 WT and T271, N342Y and Delta2N mutants to virus neutralising antibody. 2008 Retrovirology Figure HIV N342Y 32 37 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Mutated amino acids Q3R, L23A, DeltaQ44, W54G, I60A, L67A, R77Q and R90K are represented in CPK mode. 2008 Retrovirology Figure HIV I60A;L23A;L67A;Q3R;R77Q;R90K;W54G 47;25;53;20;59;68;41 51;29;57;23;63;72;45 18809675 Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice. SCID-hu Thy/Liv mice were treated by subcutaneous injection of 30 mg/kg beginning 1 day before (-1) or 3 days after (+3) inoculation and continued every fourth day (Q4D) or every seventh day (Q7D) until implant collection. 2008 The Journal of biological chemistry Figure HIV Q4D;Q7D 167;195 170;198 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. BR, BS, Bv1v3 and BR(N283T) showed greater ability to infect cells expressing low levels of CD4 (low CD4 dependence) and were less sensitive to inhibition by the anti-CD4 mAb SK3 than SPL, SB and SPL(T283N), while Bv1v2 had an intermediate phenotype. 2008 Retrovirology Figure HIV N283T;T283N 21;200 26;205 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Co-culture of effector and target cells for 30-420 minutes showed that BR, BR(N283T), BS and Bv1v3 fused more efficiently than SPL, SPL(T283N) and SB, while Bv1v2, DS17, DS17(N283T) and BaL showed an intermediate phenotype. 2008 Retrovirology Figure HIV N283T;T283N;N283T 78;136;175 83;141;180 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. DS17 and DS17(N283T) did not differ between them and showed similar sensitivity to HNG-105 than BR, BR(N283T) and BS. 2008 Retrovirology Figure HIV N283T;N283T 103;14 108;19 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. DS17 and DS17(N283T) did not differ between them but showed reduced sensitivity to BMS-378806 as compared to the BR and Env with related phenotype. 2008 Retrovirology Figure HIV N283T 14 19 Env 120 123 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. DS17 and DS17(N283T) Env were modeled based on the HIV-1JR-FL gp120 crystal structure (C and D, respectively) using the Swiss Model Server, and the models showed that the distance between T283 and Q40 would be shorter than between N283 and Q40, although both would be larger than what it is usually accepted for the formation of a hydrogen bond (3.3A). 2008 Retrovirology Figure HIV N283T 14 19 gp120;Env 62;21 67;24 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Finally, the SPL and SPL(T283N) Env were best modeled based on the HIV-1YU-2 gp120 crystal structure (E and F, respectively), and the models showed that both could potential make hydrogen bond contacts with Q40 in CD4, although the shorter distance in SPL(T283N) would suggest a greater likelihood for this to occur for mutated N283 than for wild-type T283. 2008 Retrovirology Figure HIV T283N;T283N 25;256 30;261 gp120;Env 77;32 82;35 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Pseudotypes containing BR, BR(N283T) and BS Env were significantly more sensitive than those with SPL, SB, Bv1v3 or Bv1v2. 2008 Retrovirology Figure HIV N283T 30 35 Env 44 47 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Pseudotypes containing BR, BR(N283T), BS and Bv1v3 Env were significantly less sensitive than those with SPL, SPL(T283N), SB, Sv1v3 or Sv1v2, while Bv1v2 displayed an intermediate sensitivity. 2008 Retrovirology Figure HIV N283T;T283N 30;114 35;119 Env 51 54 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Pseudotypes containing BR, BS, Bv1v3, Bv1v2 and BR(N283T) Env were significantly less sensitive to T-1249 and T-1249-BR than those with SPL and SB Env. 2008 Retrovirology Figure HIV N283T 51 56 Env;Env 58;147 61;150 18837996 The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. The brain isolate-derived DS17 Env and the DS17(N283T) mutant had a mixed phenotype with low CD4 dependence but high sensitivity to the anti-CD4 mAb. 2008 Retrovirology Figure HIV N283T 48 53 Env 31 34 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Highlighted are the roles of native TK2 or TK2 mutants in the phosphorylation of nucleoside analogues (eg, AZT) and the role of pol-gamma mutant (Y955C) in the incorporation of the active nucleoside triphosphate (eg, AZT-TP) in mtDNA replication. 2009 Laboratory investigation; a journal of technical methods and pathology Figure HIV Y955C 146 151 Pol 128 131 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. For the WT and G140S/Q148H mutant, the assay was performed with and without 500 nM RAL. 2009 Nucleic acids research Figure HIV G140S;Q148H 15;21 20;26 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The same symbols were used in panels A, B and C: (open square) wild-type NL-43; (filled square) G140S/Q148H NL-43; (filled triangle) Q148H NL-43; (open triangle) G140S NL-43; (open circle) wild-type patient; (filled circle) G140S/Q148H patient. 2009 Nucleic acids research Figure HIV G140S;G140S;G140S;Q148H;Q148H;Q148H 94;160;222;102;131;230 101;167;229;107;138;235 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. WT+RAL (open square), WT (filled square), E92Q (gray diamond), G140S (filled diamond), Q148H (filled triangle), N155H (gray circle), G140S/Q148H (filled circle), G140S/Q148H+Ral (open circle), WT + AZT (straight line). 2009 Nucleic acids research Figure HIV E92Q;G140S;G140S;G140S;N155H;Q148H;Q148H;Q148H 42;63;133;162;112;87;139;168 46;68;138;167;117;92;144;173 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Intermolecular interaction network between the helix2I-helix2II motifs forming a CA dimeric interface for (a) wild-type (146-231), (b) W184A, and (c) M185A. 2009 Biomacromolecules Figure HIV M185A;W184A 148;133 155;140 Capsid 81 83 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Intramolecular hydrogen bonding network between the turn region (residues 155-159) and helix 2 (residues 179-192) for (a) wild-type (146-231), (b) Q155N, and (c) E159D. 2009 Biomacromolecules Figure HIV E159D;Q155N 160;145 167;152 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Structural comparison and characterization of wild-type CA (146-231) and its mutants (Q155N and E159D) at the MHR region. 2009 Biomacromolecules Figure HIV E159D;Q155N 96;86 101;92 Capsid 56 58 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Structural comparison and characterization of wild-type CA (146-231) and its mutants (W184A and M185A) at the helix 2 region. 2009 Biomacromolecules Figure HIV M185A;W184A 96;86 101;92 Capsid 56 58 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Variations of pairwise interface residue distances at the selected positions of 192I-192II, 185I-185II, 184I-184II, and 180I-180II between the helix2I-helix2II motifs for (a) wild-type, (b) W184A, and (c) M185A, where I and II indicate different CTD monomers. 2009 Biomacromolecules Figure HIV M185A;W184A 203;188 210;195 19199580 Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain. Variations of pairwise residue distances at the selected positions of 155-159, 155-194, and 155-195 within the same CTD monomer for (d) wild-type (146-231), (e) Q155N, and (f) E159D. 2009 Biomacromolecules Figure HIV E159D;Q155N 174;159 181;166 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. MW (molecular mass standards in kilo daltons are shown on the left); b/cWT, (subtype B/C HIV-1 RT wild-type); b/cK65R, (subtype B/C HIV-1 RT harboring K65R); b/cK65R+M184V, (subtype B/C HIV-1 RT harboring K65R+M184V). 2009 Retrovirology Figure HIV K65R;K65R;K65R;M184V;M184V 151;205;161;166;210 155;209;165;171;215 RT;RT;RT 95;138;192 97;140;194 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. M50_13B_K101E is boxed in both panels. 2009 PloS one Figure HIV K101E 8 13 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The arrow indicates the closer relatedness between the mother sequence cluster harboring M50_13B_K101E (boxed) and the child cluster. 2009 PloS one Figure HIV K101E 97 102 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The formation of a net (pointed by the arrow) in A depicts genetic relatedness between sequence M50_13B_K101E and the child viral sequence cluster. 2009 PloS one Figure HIV K101E 104 109 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Black bars, BS clones carrying patient-derived Gag, PR, and RT; light grey bars, clones in which mutation A431V (for VIS13 and VIS 18) or I437V (for VIS16) was reverted back to wild-type in patient-derived Gag in BS clones by site-directed mutagenesis; dark grey bars, XS clones carrying NL4-3 Gag in the presence of patient-derived PR and RT; white bars, clones in which mutation A431V (for VIS13 and VIS 18) or I437V (for VIS16) were inserted in NL4-3-derived Gag in XS clones by site-directed mutagenesis. 2009 PLoS pathogens Figure HIV A431V;A431V;I437V;I437V 106;381;138;413 111;386;143;418 Gag;Gag;Gag;Gag;PR;PR;RT;RT 47;206;294;462;52;333;60;340 50;209;297;465;54;335;62;342 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. Mutation of a single amino acid (T45I) leads to insensitivity to Vpu and persistence of tetherin protein. 2009 PLoS pathogens Figure HIV T45I 33 37 Vpu 65 68 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. Mutation of positively selected residues I26V, V30G, I36L, T45I (DeltaTHN) in the trans-membrane region of human tetherin results in reduced sensitivity to Vpu whilst maintaining antiviral activity. 2009 PLoS pathogens Figure HIV I26V;I36L;T45I;V30G 41;53;59;47 45;57;63;51 Vpu 156 159 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. Mutation of positively selected residues I26V, V30G, I36L, T45I (Quad) in the trans-membrane region of human tetherin results in reduced sensitivity to Vpu whilst maintaining similar antiviral activity. 2009 PLoS pathogens Figure HIV I26V;I36L;T45I;V30G 41;53;59;47 45;57;63;51 Vpu 152 155 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. Mutation T45I in the trans-membrane region of human tetherin results in insensitivity to Vpu whilst maintaining antiviral activity. 2009 PLoS pathogens Figure HIV T45I 9 13 Vpu 89 92 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. A, Results of K103N allele-specific PCR on wild-type template. 2009 Journal of acquired immune deficiency syndromes (1999) Figure HIV K103N 14 19 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. B, Results of Y181C allele-specific PCR on wild-type template. 2009 Journal of acquired immune deficiency syndromes (1999) Figure HIV Y181C 14 19 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Background levels of K103N and Y181C allele-specific PCR assays. 2009 Journal of acquired immune deficiency syndromes (1999) Figure HIV K103N;Y181C 21;31 26;36 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Viability of cells 24 hrs post electroporation with WT, Delta-C term, R90K DeltaSRS or GFP RNAs were 93%, 93%, 94% 94% and 94% respectively. 2009 PloS one Figure HIV R90K 70 74 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Vpr R90K mutation restores IL-12 secretion from DC. 2009 PloS one Figure HIV R90K 4 8 Vpr 0 3 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Vpr wild-type (WT), VPR lacking C-terminus (DeltaCterm), Vpr R90K, Vpr R90G, Vpr R90S RNAs or GFP RNA alone were electroporated into DC and levels of IL-12 detected in DC supernatants 24 hrs post-electroporation. 2009 PloS one Figure HIV R90G;R90K;R90S 71;61;81 75;65;85 Vpr;Vpr;Vpr;Vpr;Vpr 0;20;57;67;77 3;23;60;70;80 19552592 Analysis of HIV type 1 gp41 and enfuvirtide susceptibility among men in the United States who were HIV infected prior to availability of HIV entry inhibitors. Some ENF resistance mutations were detected as mixtures with the wild-type (HXB2) codons (V38A in samples #1526 and #5712; N43K and L45M in sample #2047); mutations in the other samples were present as the major sequence (no mixture detected). 2009 AIDS research and human retroviruses Figure HIV L45M;N43K;V38A 132;123;90 136;127;95 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. (B) Infection of U373-MAGI-CXCR4CEM cells with wild type as well as Y271A and I274A mutants of live HIV-1 virus. 2009 PloS one Figure HIV I274A;Y271A 78;68 83;73 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. (B) Pr160Gag-pol, Pr55Gag and CA p24 were detected in wild type (WT) as well as Y271A and I274A mutant pseudoviruses produced in the absence (0) or presence of 0.2 and 2 microM protease inhibitor (indinavir) by Western blotting using mouse monoclonal anti-CA. 2009 PloS one Figure HIV I274A;Y271A 90;80 95;85 PR;Pol;p24;Capsid;Capsid;PR;PR 177;13;33;30;256;4;18 185;16;36;32;258;6;20 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. (B) The subcellular distribution of Pr160Gag-pol in HeLa cells transfected with pseudoviral vectors for wild type (WT) RT or Y271A and I274A mutants were further detected by immunofluorescence staining using mouse monoclonal anti-integrase primary antibody and Texas Red dye-conjugated rabbit anti-mouse IgG secondary antibody. 2009 PloS one Figure HIV I274A;Y271A 135;125 140;130 IN;Pol;PR;RT 230;45;36;119 239;48;38;121 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. (C) Infection of MT2 cells with wild type as well as Y271A and I274A mutants of live HIV-1. 2009 PloS one Figure HIV I274A;Y271A 63;53 68;58 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. (C) Pr160Gag-pol and its subunits RT p66 and p51 were detected in wild type (WT) as well as Y271A and I274A mutant pseudoviruses produced in the absence (0) or presence of 0.2 and 2 microM protease inhibitor (indinavir) by Western blotting using mouse monoclonal anti-RT antibody. 2009 PloS one Figure HIV I274A;Y271A 102;92 107;97 PR;Pol;PR;RT;RT 189;13;4;34;268 197;16;6;36;270 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. The assays showed that both RT activity and protein in mutant pseudoviruses Y271A and I274A were almost undetectable. 2009 PloS one Figure HIV I274A;Y271A 86;76 91;81 RT 28 30 19777131 Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity. Docked orientations of nevirapine (green), 9 (yellow), 5, and 6 (atom type color - carbon: grey, chloride: green, hydrogen: white, nitrogen: blue, oxygen: red and sulfur: yellow) in WT (a), K103N (b), and Y181C (c) binding pockets. 2009 Beilstein journal of organic chemistry Figure HIV K103N;Y181C 190;205 195;210 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. A, stereoview showing the binding of TFV-DP (cyan/orange) to K65R mutant RT (gray) in the K65R RT dsDNA TFV-DP ternary complex structure. 2009 The Journal of biological chemistry Figure HIV K65R;K65R 61;90 65;94 RT;RT 73;95 75;97 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. B, stereoview showing the binding of dATP (green/orange) to K65R mutant RT (gray) in the K65R RT dsDNA dATP ternary complex structure. 2009 The Journal of biological chemistry Figure HIV K65R;K65R 60;89 64;93 RT;RT 72;94 74;96 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Binding of TFV-DP and dATP to K65R RT. 2009 The Journal of biological chemistry Figure HIV K65R 30 34 RT 35 37 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Comparison of binding of TFV-DP and dATP to K65R RT dsDNA. 2009 The Journal of biological chemistry Figure HIV K65R 44 48 RT 49 51 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Shown is stacking of the guanidinium plane of Arg65 and guanidinium plane of Arg72 and adenine base in K65R RT dsDNA dATP (B) and K65R RT dsDNA TFV-DP (C) ternary structures. 2009 The Journal of biological chemistry Figure HIV K65R;K65R 103;130 107;134 RT;RT 108;135 110;137 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Superposition of excision-enhancing mutation or TAM (M41L, D67N, K70R, T215Y, and K219Q) RT dsDNA AZTppppA structure4 on K65R RT dsDNA dATP structure at their dNTP-binding sites; AZTppppA is the product of AZT monophosphate by ATP-mediated excision. 2009 The Journal of biological chemistry Figure HIV D67N;K219Q;K65R;K70R;M41L;T215Y 59;82;121;65;53;71 63;87;125;69;57;76 RT;RT 89;126 91;128 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The mutated residues Arg70 and Tyr215 are from the crystal structure of excision-enhancing mutation RT complex, whereas M184V was modeled based on the structure of the M184V RT dsDNA binary complex. 2009 The Journal of biological chemistry Figure HIV M184V;M184V 120;168 125;173 RT;RT 100;174 102;176 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The surfaces of the K65R/Arg72 platform (gray mesh) and M184V (3TC resistance mutation site; magenta mesh) form two walls on either side of the ribose ring, whereas the other end of the K65R/Arg72 platform interfaces with K70R, a primary mutation site for AZT resistance. 2009 The Journal of biological chemistry Figure HIV K65R;K65R;K70R;M184V 20;186;222;56 24;190;226;61 19838296 Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions. The vpr alleles from the LNTP (patient 5071) that were selected for subsequent functional analysis are in the box; the R77Q substitution identified in some vpr alleles is indicated in blue, while the Q65R substitution identified in the Vpr LTNP-04-2 is indicated in red. 2009 PloS one Figure HIV Q65R;R77Q 200;119 204;123 Vpr;Vpr;Vpr 4;156;236 7;159;239 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Different subpopulations containing K103N are also labeled with solid shapes. 2009 Retrovirology Figure HIV K103N 36 41 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Horizontal red bars show the percentage of all subpopulations with a single K103N mutation in the population of each week. 2009 Retrovirology Figure HIV K103N 76 81 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Horizontal red bars show the percentage of all subpopulations with drug resistant mutations (K65R, K103N, M184I, and M184V) in the population of each week. 2009 Retrovirology Figure HIV K103N;K65R;M184I;M184V 99;93;106;117 104;97;111;122 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Phylogenetic analysis of plasma HIV variants isolated from a representative subject (Subject 2) whose baseline HIV-1 RNA was 5.30 log10 copies/mL and whose baseline (pre-therapy) population genotype was wild-type and who at failure had an HIV-1 RNA of 2.87 log10 copies/mL and a population genotype of K65R + S68N/S + Y115F/Y + V118I. 2010 The Journal of antimicrobial chemotherapy Figure HIV K65R;S68N;S68S;V118I;Y115F;Y115Y 302;309;309;328;318;318 306;315;315;333;325;325 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Phylogenetic analysis of plasma HIV variants isolated from a representative subject (Subject 5) whose baseline HIV-1 RNA was 5.34 log10 copies/mL and whose baseline (pre-therapy) population genotype resistance mutations included K103K/N + Y188F/H/L/Y and who at failure had an HIV-1 RNA of 4.23 log10 copies/mL and a population genotype of M41L + D67N + K70R + M184V + T215F + K219E. 2010 The Journal of antimicrobial chemotherapy Figure HIV D67N;K103K;K103N;K219E;K70R;M184V;M41L;T215F;Y188F;Y188H;Y188L;Y188Y 347;229;229;377;354;361;340;369;239;239;239;239 351;236;236;382;358;366;344;374;250;250;250;250 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. (B) FACS analysis of CD4 expression by Jurkat (upper panel) and CD4 co-transfected 293T cells (lower panel) expressing GFP alone or together with the Vpu and Vpu S52A proteins. 2010 Retrovirology Figure HIV S52A 162 166 Vpu;Vpu 150;158 153;161 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Abbreviations, N-, Nef-defective; U-, Vpu-defective; S52A, VpuS52A. 2010 Retrovirology Figure HIV S52A 53 57 Nef;Vpu;Vpu 19;38;59 22;41;62 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Abbreviations, U-, Vpu-defective; S52A, VpuS52A. 2010 Retrovirology Figure HIV S52A 34 38 Vpu;Vpu 19;40 22;43 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Mutation of S52A impairs Vpu-mediated degradation of CD4 and tetherin. 2010 Retrovirology Figure HIV S52A 12 16 Vpu 25 28 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Vpu S52A does not impair HIV-1 release from P4-CCR5 cells. 2010 Retrovirology Figure HIV S52A 4 8 Vpu 0 3 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Vpu S52A dose-dependently counteracts tetherin in transfected 293T cells. 2010 Retrovirology Figure HIV S52A 4 8 Vpu 0 3 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Vpu S52A impairs HIV-1 replication in macrophages. 2010 Retrovirology Figure HIV S52A 4 8 Vpu 0 3 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Vpu S52A is dispensable for HIV-1 replication and cytopathicity in ex vivo infected HLT. 2010 Retrovirology Figure HIV S52A 4 8 Vpu 0 3 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Asterisks (*) indicate statistical significance (p < 0.001) between -T477A and +T477A mutant viruses, calculated using a one-tailed Student's t-test assuming equal variance. 2010 Retrovirology Figure HIV T477A;T477A 69;80 74;85 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Black and white bars indicate p51 RNH - T477A or p51 RNH + T477A mutant viruses respectively, derived from transfected 293T cells, normalized to 25 ng viral p24 at time of infection. 2010 Retrovirology Figure HIV T477A;T477A 40;59 45;64 p24 157 160 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Effect of p51 RNH +- T477A mutations on ordered intravirion processing of Gag and Gag-Pol polyproteins. 2010 Retrovirology Figure HIV T477A 21 26 GagPol;Gag 82;74 89;77 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Effect of p51 RNH +- T477A mutations on viral particle protein composition. 2010 Retrovirology Figure HIV T477A 21 26 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. In Figure 2A and 2B, WT and WT+T477A samples (two leftmost lanes) are from a different gel than the rest of the samples, as the number of wells in the electrophoresis apparatus was unable to accommodate all samples simultaneously. 2010 Retrovirology Figure HIV T477A 31 36 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Infectivity of WT and p51 RNH +- T477A mutant virus in single cycle replication assays. 2010 Retrovirology Figure HIV T477A 33 38 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Statistical significance of the T477A compensatory effect was determined for each individual mutant virus relative to its non-substituted counterpart using a one-tailed Student's t-test assuming equal variance. 2010 Retrovirology Figure HIV T477A 32 37 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Western blots of wild-type (WT) and p51 RNH +- T477A mutant viruses (1 mug viral p24) generated by transfection of 293T cells and probed with (A) anti-PR, (B) anti-RT, (C) anti-IN, and (D) anti-p24 antibodies. 2010 Retrovirology Figure HIV T477A 47 52 p24;p24;IN;PR;RT 81;194;177;151;164 84;197;179;153;166 20174661 HIV drug resistance surveillance using pooled pyrosequencing. All positive pyrosequencing reads containing L33V (a) and L33I (b) were analyzed with Sanger sequences from the 96 specimens using Neighbour-Joining (K-2-P) with 100 bootstraps. 2010 PloS one Figure HIV L33I;L33V 58;45 62;49 20174661 HIV drug resistance surveillance using pooled pyrosequencing. All positive pyrosequencing reads containing M46I (a) and F53L (b) were analyzed with Sanger sequences from the 96 specimens using Neighbour-Joining (K-2-P) with 100 bootstraps. 2010 PloS one Figure HIV F53L;M46I 58;45 62;49 20174661 HIV drug resistance surveillance using pooled pyrosequencing. All positive pyrosequencing reads containing M46L (a) and I84V (b) were analyzed with Sanger sequences from the 96 specimens using Neighbour-Joining (K-2-P) with 100 bootstraps. 2010 PloS one Figure HIV I84V;M46L 58;45 62;49 20174661 HIV drug resistance surveillance using pooled pyrosequencing. Two TDR mutations, M46L and I84V, were detected by conventional Sanger sequencing, each in one of the 96 examined specimens. 2010 PloS one Figure HIV I84V;M46L 28;19 32;23 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. A strong pausing is observed at codon 65 in subtype C, which may favor the evolution of K65R. 2009 HIV therapy Figure HIV K65R 88 92 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Facilitated selection of K65R in subtype C. 2009 HIV therapy Figure HIV K65R 25 29 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. Selection of K65R in subtype C is facilitated by a poly-A stretch between codons 63 and 65. 2009 HIV therapy Figure HIV K65R 13 17 20227665 Flexible use of nuclear import pathways by HIV-1. (A) N74D HIV-1 vectors do not require TNPO3 or RANBP2 for infection. 2010 Cell host & microbe Figure HIV N74D 2 8 20227665 Flexible use of nuclear import pathways by HIV-1. (B) Differential NUP requirements by WT HIV-1 and the N74D mutant. 2010 Cell host & microbe Figure HIV N74D 54 58 20227665 Flexible use of nuclear import pathways by HIV-1. (B) HIV-1 with the N74D mutation in CA efficiently infects nondividing HeLa cells and infection is not blocked in nondividing HeLa cells expressing mCPSF6-358. 2010 Cell host & microbe Figure HIV N74D 19 23 Capsid 36 38 20227665 Flexible use of nuclear import pathways by HIV-1. (D) N74D HIV-1 is an FIV phenocopy. 2010 Cell host & microbe Figure HIV N74D 2 8 20227665 Flexible use of nuclear import pathways by HIV-1. (E) E45A and Q63A/Q67A HIV-1 are TNPO3-independent. 2010 Cell host & microbe Figure HIV E45A;Q63A;Q67A 2;13;18 8;17;22 20227665 Flexible use of nuclear import pathways by HIV-1. (F) E45A and Q63A/Q67A HIV-1 are less sensitive to NUP depletions. 2010 Cell host & microbe Figure HIV E45A;Q63A;Q67A 2;13;18 8;17;22 20227665 Flexible use of nuclear import pathways by HIV-1. (G) CPSF6-358 restriction of E45A or Q63A/Q67A HIV-1 is cell-cycle dependent. 2010 Cell host & microbe Figure HIV E45A;Q63A;Q67A 29;37;42 33;41;46 20227665 Flexible use of nuclear import pathways by HIV-1. 293T cells expressing MIGR1-mCPSF6 or MIGR1-mCPSF6-358 and infected with HIV-HSA/VSV-G or HIVIN/D116N-HSA/VSV-G carrying an active site mutation in the viral IN were lysed at various times to measure the amount of viral DNA using primers for specific steps in reverse transcription. 2010 Cell host & microbe Figure HIV D116N 96 101 RT;IN 260;158 281;160 20227665 Flexible use of nuclear import pathways by HIV-1. 293T.LPC-CPSF6-358-HA cells were challenged with increasing volumes of HIVNLdE-luc/VSV-G or HIVNLdE CA N74D-luc/VSV-G and then with a fixed amount of WT HIV-RFP/VSV-G. 2010 Cell host & microbe Figure HIV N74D 103 107 Capsid 100 102 20227665 Flexible use of nuclear import pathways by HIV-1. By contrast, depletion of NUP155 limits N74D HIV-1 and FIV infection. 2010 Cell host & microbe Figure HIV N74D 40 44 HIV-FIV coinfections 55 68 20227665 Flexible use of nuclear import pathways by HIV-1. Cells were infected with HIVNLdE-luc/VSV-G, HIVNLdE CA N74D-luc/VSV-G, HIVNLdE CA E45A-luc/VSV-G, or HIVNLdE CA Q63A/Q67A-luc/VSV-G and lucifease activity from lysates was measured 48 h later. 2010 Cell host & microbe Figure HIV Q63A;Q67A;E45A;N74D 112;117;82;55 116;121;86;59 Capsid;Capsid;Capsid 52;79;109 54;81;111 20227665 Flexible use of nuclear import pathways by HIV-1. Depletion of TNPO3, RANBP2, and NUP153 diminishes WT but not N74D HIV-1 infection. 2010 Cell host & microbe Figure HIV N74D 61 65 20227665 Flexible use of nuclear import pathways by HIV-1. HeLa cells stably transduced with control shRNA or TNPO3 shRNA vectors were infected with WT HIV-1 or different CA mutant HIV-1 (HIVNLdE-luc/VSV-G, HIVNLdE CA N74D-luc/VSV-G, HIVNLdE CA E45A-luc/VSV-G, or HIVNLdE CA Q63A/Q67A-luc/VSV-G). 2010 Cell host & microbe Figure HIV Q63A;Q67A;E45A;N74D 216;221;186;159 220;225;190;163 Capsid;Capsid;Capsid;Capsid 112;156;183;213 114;158;185;215 20227665 Flexible use of nuclear import pathways by HIV-1. HeLa cells that contain only the empty vector or cells that express mCPSF6-358 and HeLa cells transduced with control shRNA vector or TNPO3 shRNA were infected with either WT HIV-1 or N74D mutant vectors that express a luciferase reporter (HIVNLdE-luc/VSV-G or HIVNLdE CA N74D-luc/VSV-G, respectively). 2010 Cell host & microbe Figure HIV N74D;N74D 184;272 188;276 Capsid 269 271 20227665 Flexible use of nuclear import pathways by HIV-1. HeLa.MIGR1 and HeLa.MIGR1-mCPSF6-358 cells maintained in the presence or absence of aphidicolin were infected in duplicate with MLV, HIVNLdE-luc/VSV-G, HIVNLdE CA N74D-luc/VSV-G, HIVNLdE CA E45A-luc/VSV-G, or HIVNLdE CA Q63A/67A-luc/VSV-G. 2010 Cell host & microbe Figure HIV Q63A;E45A;N74D 220;190;163 224;194;167 Capsid;Capsid;Capsid 160;187;217 162;189;219 20227665 Flexible use of nuclear import pathways by HIV-1. HeLa.MIGR1 and HeLa.MIGR1-mCPSF6-358 cells were maintained in the presence or absence of aphidicolin and infected with MLV, HIVNLdE-luc/VSV-G, or HIVNLdE CA N74D-luc/VSV-G. 2010 Cell host & microbe Figure HIV N74D 157 161 Capsid 154 156 20227665 Flexible use of nuclear import pathways by HIV-1. Infections with WT or N74D HIV-RFP/VSV-G were performed in duplicate and assayed 48 h later by FACS. 2010 Cell host & microbe Figure HIV N74D 22 26 20227665 Flexible use of nuclear import pathways by HIV-1. Middle panel, HeLa.control_shRNA or HeLa.TNPO3_shRNA cells were infected in duplicates with WT HIV-RFP/VSV-G, N74D HIV-RFP/VSV-G, or FIV-GFP/VSV-G. 2010 Cell host & microbe Figure HIV N74D 110 114 20227665 Flexible use of nuclear import pathways by HIV-1. N74D HIV-RFP/VSV-G infection of 293T cells transiently transfected with empty vector (control) or HA-tagged constructs expressing human CPSF6-300, CPSF6-358, or CPSF6 (encoding the full length 72 kD isoform). 2010 Cell host & microbe Figure HIV N74D 0 4 20227665 Flexible use of nuclear import pathways by HIV-1. N74D HIV-RFP/VSV-G or luciferase vectors (HIVNLdE-luc/VSV-G or HIVNLdE CA N74D-luc/VSV-G). 2010 Cell host & microbe Figure HIV N74D;N74D 74;0 78;4 Capsid 71 73 20227665 Flexible use of nuclear import pathways by HIV-1. Recombinant WT and N74D CA-NC complexes were incubated with lysates from 293T cells transfected with HA-tagged constructs expressing CPSF6-300, CPSF6-358, or rhTRIM5alpha. 2010 Cell host & microbe Figure HIV N74D 19 23 NC;Capsid 27;24 29;26 20227665 Flexible use of nuclear import pathways by HIV-1. Right panel, HeLa cells transiently transfected with nontargeting and NUP targeting siRNA were infected in duplicates with WT HIV-RFP/VSV-G, N74D HIV-RFP/VSV-G, or FIV-GFP/VSV-G. 2010 Cell host & microbe Figure HIV N74D 141 145 20227665 Flexible use of nuclear import pathways by HIV-1. Statistical analysis was performed by Student's t test; *p < 0.05 and **p <0.01 versus WT or N74D HIV-1 infection of respective control infected cells. 2010 Cell host & microbe Figure HIV N74D 93 97 20227665 Flexible use of nuclear import pathways by HIV-1. Statistical analysis was performed by Student's t test; *p = 0.0205, **p = 0.0009, and ***p < 0.0001 relative WT or N74D HIV-1 infection of respective control infected cells. 2010 Cell host & microbe Figure HIV N74D 116 120 20227665 Flexible use of nuclear import pathways by HIV-1. Two days after siRNA transfection, the transfected cells were infected with 1.5 and 3.0 mul of WT or N74D HIV-RFP/VSV-G and assayed 48 h later by FACS. 2010 Cell host & microbe Figure HIV N74D 101 105 20227665 Flexible use of nuclear import pathways by HIV-1. WT and N74D HIV-1 require different nuclear pore factors. 2010 Cell host & microbe Figure HIV N74D 7 11 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. (a) Charged mutations (colored spheres) on HIVgp41 (gray ribbon) for V38E (red), I37K (blue), and Q40K (blue) relative to negative (red = GLU, ASP) and positive (blue = LYS) charged residues on T20 (orange ribbon). 2010 Biochemistry Figure HIV I37K;Q40K;V38E 81;98;69 85;102;73 Asp 143 146 20230061 Origins of resistance to the HIVgp41 viral entry inhibitor T20. Solid arrows indicate initial I37K results while dashed arrows indicate I37K results obtained using a different random seed. 2010 Biochemistry Figure HIV I37K;I37K 30;72 34;76 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. (B) Schematic summary on H69E containing mutants and their relative Gag processing efficiencies. 2010 Retrovirology Figure HIV H69E 25 29 Gag 68 71 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Charge substitutions of surface residues did not restore the inhibitory effect of H69E on protease autoprocessing. 2010 Retrovirology Figure HIV H69E 82 86 PR 90 98 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Cysteine 95 and other residues dampened the inhibitory effect of H69E on protease autoprocessing in transfected mammalian cells. 2010 Retrovirology Figure HIV H69E 65 69 PR 73 81 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Schematic illustration of constructs with or without H69E mutation. 2010 Retrovirology Figure HIV H69E 53 57 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. The chromatin bound and non-chromatin-bound fractions of YFP-IN wild type or V165A were showed as indicated. 2010 Virology journal Figure HIV V165A 77 82 IN 61 63 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. The lentiviral shRNA-mediated LEDGF/p75 stable knockdown 293T cells were transfected with 20 nM si-LEDGF for 48 h and further transfected with YFP-IN wild type or mutant V165A and were analyzed for its chromatin binding affinity. 2010 Virology journal Figure HIV V165A 170 175 IN 147 149 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. For G190S, p24 concentrations of some replicate cultures of the G190S mutant in 20 nM EFV appeared to be higher than the no-drub control, however, this apparent different was not statistically significant (95% confidence intervals cross 1.00). 2010 Virology Figure HIV G190S;G190S 4;64 9;69 p24 11 14 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. For K101E no increase in mean p24 antigen concentration relative to the no-drug control was observed at any of the EFV concentrations tested. 2010 Virology Figure HIV K101E 4 9 p24 30 33 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Graphs represent the results of EFV susceptibility assays of the NNRTI-resistant mutants K101E+G190S (panel A), G190S (panel B), K101E (panel C), and M230L (panel D). 2010 Virology Figure HIV G190S;G190S;K101E;K101E;M230L 95;112;89;129;150 100;117;94;134;155 NNRTI 65 70 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Growth competition assays of virus with the D10 RT versus G190S in NL4-3, in the presence of no drug (closed diamonds), or 100 nM (closed squares), 200 nM (closed triangles), or 400 nM (closed circles) of EFV. 2010 Virology Figure HIV G190S 58 63 RT 48 50 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Impact of the nucleoside resistance mutation L74V on replication by (K101E+G190S) NL4-3 in the absence and presence of EFV. 2010 Virology Figure HIV G190S;K101E;L74V 75;69;45 80;74;49 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Impact of the thymidine analog mutations (M41L+T215Y) on replication of HIV-1 containing the NNRTI resistance mutations (K101E+G190S) in an NL4-3 backbone. 2010 Virology Figure HIV G190S;K101E;M41L;T215Y 127;121;42;47 132;126;46;52 NNRTI 93 98 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Panel A, Growth competition experiment with NL4-3 virus containing the D10 RT sequence (with the resistance mutations [K101E+G190S] + [M41L+T215Y]), versus the reference strain, (K101E+G190S) in an NL4-3 RT backbone. 2010 Virology Figure HIV G190S;G190S;K101E;K101E;M41L;T215Y 125;185;119;179;135;140 130;190;124;184;139;145 RT;RT 75;204 77;206 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Panel B, Growth competition experiment with NL4-3 virus containing the D10 RT sequence versus the reference strain, G190S in an NL4-3 RT backbone. 2010 Virology Figure HIV G190S 116 121 RT;RT 75;134 77;136 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Panels A and B, growth competition assays of virus with the D10 RT in which K101E (panel A) or [M41L+T215Y] (panel B) were reverted to wild-type, competed against NL4-3 with the intact D10 RT as a reference strain. 2010 Virology Figure HIV K101E;M41L;T215Y 76;96;101 81;100;106 RT;RT 64;189 66;191 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Panels A and B, growth competition experiments of ([K101E+G190S] + [M41L+T215Y]) in an NL4-3 RT backbone, in the absence of drug. 2010 Virology Figure HIV G190S;K101E;M41L;T215Y 58;52;68;73 63;57;72;78 RT 93 95 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Reference strains are NL4-3 (K101E+G190S) in panel A, and NL4-3 (G190S) in panel B. 2010 Virology Figure HIV G190S;G190S;K101E 35;65;29 40;70;34 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Relative replication fitness of D10 RT versus G190S in NL4-3 in the absence and presence of EFV. 2010 Virology Figure HIV G190S 46 51 RT 36 38 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Relative replication fitness of K101E+G190S, in an NL4-3 backbone, in the absence and presence of EFV. 2010 Virology Figure HIV G190S;K101E 38;32 43;37 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The graph represents the relative proportion of the double mutant K101E+G190S relative to the reference strain G190S NL4-3, as determined by bulk sequence analysis in growth competition experiments, as outlined in Materials and Methods. 2010 Virology Figure HIV G190S;G190S;K101E 72;111;66 77;116;71 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The peak EFV-dependent stimulation concentration for D10 with M41L+T215Y back mutated to wild-type was 3200 nM EFV and the fold stimulation was 100.73+-28.8. 2010 Virology Figure HIV M41L;T215Y 62;67 66;72 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. 2A: 3'-Processing activity of IN WT and IN Y143C/R mutants. 2010 PloS one Figure HIV Y143C;Y143R;Y143C;Y143R 44;44;43;43 51;51;50;50 IN;IN 30;40 32;42 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. 2B: Strand transfer activity of IN WT and IN Y143C/R mutants. 2010 PloS one Figure HIV Y143C;Y143R 45;45 52;52 IN;IN 32;42 34;44 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Comparison of IN WT and IN Y143C/R activities in vitro. 2010 PloS one Figure HIV Y143C;Y143R 27;27 34;34 IN;IN 14;24 16;26 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Concerted integration activity of IN WT and IN Y143C/R mutants. 2010 PloS one Figure HIV Y143C;Y143R 47;47 54;54 IN;IN 34;44 36;46 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Increasing amounts of IN WT or mutants IN Y143C or Y143R were incubated in presence of donor and acceptor DNA. 2010 PloS one Figure HIV Y143C;Y143R 42;51 47;56 IN;IN 22;39 24;41 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Sensitivity to RAL of IN WT and IN Y143C/R mutants in a 3'-processing assay. 2010 PloS one Figure HIV Y143C;Y143R 35;35 42;42 IN;IN 22;32 24;34 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Sensitivity to RAL of IN WT and IN Y143C/R mutants in a concerted integration assay. 2010 PloS one Figure HIV Y143C;Y143R 35;35 42;42 IN;IN 22;32 24;34 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Sensitivity to RAL of IN WT and IN Y143C/R mutants in a strand transfer assay. 2010 PloS one Figure HIV Y143C;Y143R 35;35 42;42 IN;IN 22;32 24;34 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. V179F is not included in this graphic; despite a significant positive correlation with Y181C, the comparison produces a high Jaccard dissimilarity coefficient, causing a misleading placement in multidimensional scaling. 2010 The Journal of antimicrobial chemotherapy Figure HIV Y181C;V179F 87;0 92;5 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. b, replication kinetics of S16A/P17A variant in Jurkat and CEM cells. 2010 The Journal of biological chemistry Figure HIV P17A;S16A 32;27 36;31 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. Briefly, MAGIC-5 cells (1 x 106 cells) were exposed to WT or S16A/P17A virus (2.5 ng of HIV-1 RT) and harvested at 1 day postinfection. 2010 The Journal of biological chemistry Figure HIV P17A;S16A 66;61 70;65 RT 94 96 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. d, effect of GST-Pin1 (W34A/K63A) on uncoating. 2010 The Journal of biological chemistry Figure HIV K63A;W34A 28;23 32;27 PI 17 19 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. In vitro uncoating activities after incubating GST-Pin1 (W34A/K63A) with CA cores for 1 h. 2010 The Journal of biological chemistry Figure HIV K63A;W34A 62;57 66;61 Capsid;PI 73;51 75;53 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. MAGIC-5 cells were incubated with WT HIV-1(VSV-G) or S16A/P17A HIV-1(VSV-G) at 4 C for 30 min and then at 37 C for 4 h. 2010 The Journal of biological chemistry Figure HIV P17A;S16A 58;53 62;57 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. The S16A/P17A CA mutant shows impaired uncoating process. 2010 The Journal of biological chemistry Figure HIV P17A;S16A 9;4 13;8 Capsid 14 16 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Extension from a mismatched terminus by wild-type, K65R and K65A reverse transcriptases. 2010 Journal of molecular biology Figure HIV K65A;K65R 60;51 64;55 RT 65 87 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Single dNTP incorporation by wild-type and K65A reverse transcriptases. 2010 Journal of molecular biology Figure HIV K65A 43 47 RT 48 70 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Proportion of UDPS reads containing K65R in 18 subtype C and 27 subtype B viruses from anti retroviral-naive individuals. 2010 PloS one Figure HIV K65R 36 40 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The figure shows the mean proportion of K65R for the duplicate runs. 2010 PloS one Figure HIV K65R 40 44 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The median proportion of K65R reads per sample were 0.25% for subtype B and 1.04% for subtype C. 2010 PloS one Figure HIV K65R 25 29 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. A) The perturbation of Val82 to Thr82. 2010 Journal of chemical theory and computation Figure HIV V82T 23 37 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. B) The perturbation of Ile84 to Val84. 2010 Journal of chemical theory and computation Figure HIV I84V 23 37 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. Perturbation of Val82 to Thr and Ile84 to Val. 2010 Journal of chemical theory and computation Figure HIV I84V;V82T 33;16 45;28 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Lower plasma viral loads in B*57/*5801-positive subjects with T242N. 2010 PloS one Figure HIV T242N 62 67 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Plasma viral loads of patients grouped by the presence or absence of B*57/*5801 with T242N with or without the compensatory H219 and M228 mutations. 2010 PloS one Figure HIV T242N 85 90 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Panel A shows the template structure of the N-terminal domain of the HIV-1 CA; panel B shows the model of the domain structure with the G116E mutation. 2010 Retrovirology Figure HIV G116E 136 141 Capsid 75 77 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Structural model of the N-terminal domain of HIV-1 CA with G116E substitution. 2010 Retrovirology Figure HIV G116E 59 64 Capsid 51 53 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The differences in percent infection between the wild type and G116E were statistically evaluated by unpaired t test (**; P < 0.01). 2010 Retrovirology Figure HIV G116E 63 68 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The differences in percent infection between WT-GFP and G116E-GFP, or 4/5S6/7S-GFP and 4/5SG116E6/7S-GFP were statistically evaluated by unpaired t test (*: P < 0.05, **; P < 0.01). 2010 Retrovirology Figure HIV G116E 56 61 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Frequency of resistance drug resistance mutations M184V, T215Y, L210W and T215C/D before, during and after treatment. 2010 PloS one Figure HIV L210W;M184V;T215C;T215D;T215Y 64;50;74;74;57 69;55;81;81;62 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (A) (-) cPPT HIV-1 vectors containing different percentages of WT RT to M184I RT in a single viral particle (100% M184I, 90% M184I to 10% WT, 50% M184I to 50% WT, 10% M184I to 90% WT, 100% WT) were prepared. 2010 Virology Figure HIV M184I;M184I;M184I;M184I;M184I 72;114;125;146;167 77;119;130;151;172 RT;RT 66;78 68;80 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (A) 3TC dose dependence of the M184I (+) and (-) cPPT vectors in HLFs pretreated with 1mM dN. 2010 Virology Figure HIV M184I 31 36 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (A) The transduction efficiency of the M184I (+) and (-) cPPT HIV-1 vectors in dividing HLFs in the presence of 50microM 3TC. 2010 Virology Figure HIV M184I 39 44 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (A) Transduction efficiency of (+) and (-) cPPT M184I vectors in HLFs cultured in 10% serum, 0.2% serum and 0.2% serum with 1mM dNs. 2010 Virology Figure HIV M184I 48 53 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (B) 3TC dose dependence of the M184I (+) and (-) cPPT vectors. 2010 Virology Figure HIV M184I 31 36 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (B) Quantitative 2LTR circle PCR assay of the (+) and (-) cPPT M184I vector in the serum-starved HLFs. 2010 Virology Figure HIV M184I 63 68 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (B) The transduction of the M184I (-) cPPT vectors in dividing HLFs in the presence and absence of 1mM dC or a mixture of 1mM dA, dT, and dG. 2010 Virology Figure HIV M184I 28 33 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (C) AZT dose dependence of the M184I (+) and (-) cPPT vectors. 2010 Virology Figure HIV M184I 31 36 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (C) The LTR/gag late reverse transcription product synthesized from the 3' LTR was measured for the (+) and (-) M184I vector in the serum-starved HLF at 48 hours post transduction as described in Materials and Procedures. 2010 Virology Figure HIV M184I 110 117 RT;3'LTR;LTR;Gag 21;72;8;12 42;78;11;15 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. (D) Nevirapine dose dependence on the M184I (+) and (-) cPPT vectors. 2010 Virology Figure HIV M184I 38 43 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Compensation of the transduction defect of the M184I (-) cPPT HIV-1 vector by the incorporation of WT HIV-1 RT. 2010 Virology Figure HIV M184I 47 52 RT 108 110 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Effect of cPPT mutation on the transduction efficiency and proviral DNA synthesis of HIV-1 vector harboring M184I mutant RTs. 2010 Virology Figure HIV M184I 108 113 RT 121 124 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Effect of dN treatment on M184I (-) HIV-1 vector sensitivity to 3TC. 2010 Virology Figure HIV M184I 26 31 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Genomic DNA of serum-starved HLFs transduced with the M184I virus was prepared at 48 hours post transduction and used for the quantitative 2LTR PCR to monitor the kinetics of the proviral DNA synthesis and normalized with genomic cellular DNA as previously described. 2010 Virology Figure HIV M184I 54 59 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. HLFs were transduced with an equal p24 level of the (-) cPPT M184I RT vectors in dividing HLFs pretreated with varying concentrations of 3TC. 2010 Virology Figure HIV M184I 61 66 p24;RT 35;67 38;69 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. HLFs were transduced with an equal p24 level, 2.77x105 pg of (+) and (-) cPPT M184I RT HIV-1 vectors, and the transduction efficiency was determined as described in Figure 1B. 2010 Virology Figure HIV M184I 78 83 p24;RT 35;84 38;86 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. (A) Plot of inhibition of FS products obtained with N155H IN with increasing concentrations of various STIs. 2010 Biochemistry Figure HIV N155H 52 57 IN 58 60 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. (B) Plot of inhibition of FS products obtained with Q148H IN with increasing concentrations of various STIs. 2010 Biochemistry Figure HIV Q148H 52 57 IN 58 60 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. (C) Graphical representation of cross-resistance for various inhibitors against N155H and Q148H. 2010 Biochemistry Figure HIV N155H;Q148H 80;90 85;95 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. (D) Kinetics of formation of SC, H-SC, and STC with N155H IN. 2010 Biochemistry Figure HIV N155H 52 57 IN 58 60 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. (E) Aliquots of the above experiments with wt and N155H IN were deproteinized and the quantities of FS products were determined and plotted. 2010 Biochemistry Figure HIV N155H 50 55 IN 56 58 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Concerted integration activity is reduced in Q148H. 2010 Biochemistry Figure HIV Q148H 45 50 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Fold changes in IC50 value for FS products obtained with N155H and Q148H IN relative to wt IN were plotted. 2010 Biochemistry Figure HIV N155H;Q148H 57;67 62;72 IN;IN 73;91 75;93 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. IC50 values for inhibiting the FS products obtained with N155H and Q148H IN by various inhibitors were compared with the IC50 values obtained with wt IN (Table 1). 2010 Biochemistry Figure HIV N155H;Q148H 57;67 62;72 IN;IN 73;150 75;152 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In panel (A) wt IN (20 nM) and in panel (B) N155H IN (30 nM) were pre-assembled with 5'-32P end-labeled 1.6 kb U5 blunt-ended DNA (0.5 nM) for 15 min at 14 C. 2010 Biochemistry Figure HIV N155H 42 49 IN;IN 16;50 18;52 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Inhibition profile of concerted FS product obtained from N155H and Q148H IN with various STIs. 2010 Biochemistry Figure HIV N155H;Q148H 57;67 62;72 IN 73 75 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. N155H IN possesses slower assembly and concerted integration kinetics in comparison to wt IN. 2010 Biochemistry Figure HIV N155H 0 5 IN;IN 6;90 8;92 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. N155H or Q148H IN (30 nM) were pre-assembled with 5'-32P end-labeled 1.6 kb U5 DNA substrate (0.5 nM) at 14 C for 15 min. 2010 Biochemistry Figure HIV Q148H;N155H 9;0 14;5 IN 15 17 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Panel A and B shows the products obtained with N155H and Q148H IN, respectively. 2010 Biochemistry Figure HIV N155H;Q148H 47;57 52;62 IN 63 65 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Structurally diverse STIs are able to trap SC and H-SC formed with N155H and Q148H IN. 2010 Biochemistry Figure HIV N155H;Q148H 67;77 72;82 IN 83 85 20825656 Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. NL4-3 and NLDeltaSL1 carrying the G913A or C1907T mutations were normalized with p24 amount and used to infect PM-1 cells. 2010 Retrovirology Figure HIV C1907T;G913A 43;34 49;39 p24 81 84 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. of 100) of ROD or ROD-Q91R + I175M variant in the presence of serial RAL dilutions ranging from 3.763 x 10-5 nM to 20 nM. 2010 Retrovirology Figure HIV I175M;Q91R 29;22 34;26 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Phenotypic impact of mutations Q91R and I175M on susceptibility to RAL (A) and on viral titers in vitro (B). 2010 Retrovirology Figure HIV I175M;Q91R 40;31 45;35 21114823 Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. The titers are only shown for the two last drug increases, when the variant carrying Q91R and I175M mutations was selected. 2010 Retrovirology Figure HIV I175M;Q91R 94;85 99;89 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Primary CD4 T cells were infected with HXB2 containing wild-type HIV protease, or protease containing the mutations L90M, I54V, or V82A, and analyzed for (A) cell viability by ATP production, (B) P24 production, and (C) TUNEL positivity in the infected (P24 +), or (D) uninfected (P24-) subsets. 2010 PLoS pathogens Figure HIV I54V;L90M;V82A 122;116;131 126;120;135 PR;PR;p24;p24;p24 69;82;196;254;281 77;90;199;257;284 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. This activity is absent in the D25G protease inactive construct, and is reduced in the T26S catalytically impaired construct (B). 2010 PLoS pathogens Figure HIV D25G;T26S 31;87 35;91 PR 36 44 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Plasma HIV-1 RNA level (a-d), and V38A mutant virus proportion (e-h), for different V38A mutant virus fitness costs (a,e), initial V38A mutant virus proportion (b,f), initial T cell counts (c,g) and T cell source rate (d,h). 2010 PLoS computational biology Figure HIV V38A;V38A;V38A 34;84;131 38;88;135 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. Plasma HIV-1 RNA level (a-e), and V38A mutant virus proportion (f-j), for different V38A mutant virus fitness costs (a,f), initial V38A mutant virus proportion (b,g), initial T cell counts (c,h), T cell source rate (d,i) and ENF efficacy against ENF-resistant virus (e,j). 2010 PLoS computational biology Figure HIV V38A;V38A;V38A 34;84;131 38;88;135 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. Shown are the predicted susceptibilities for the eight NRTIs covered by the model for two sets of HIV mutant strains; K65R+M184V (panel A), and M41L+L210W+T215Y (Panel B). 2010 PloS one Figure HIV K65R;L210W;M184V;M41L;T215Y 118;149;123;144;155 122;154;128;148;160 NRTI 55 60 21179544 Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1 virus to reverse transcriptase inhibitors. The figure represents the computed susceptibilities for all mutation combinations occurring in the data-set; red symbols represent predictions for the seven RT variants in the data-set that contained the double mutations K65R+M184V; green symbols represent the susceptibilities for 153 variants containing the triple mutations M41L+L210W+T215; the blue symbols represent predictions for 568 other RT variants in the data-set retrieved from the Stanford HIV database. 2010 PloS one Figure HIV K65R;L210W;M184V;M41L 221;332;226;327 225;337;231;331 RT;RT 157;397 159;399 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. (E) The amplitudes of the burst phases from the dATP reactions shown in panels A (WT, ) and B (K70Q/Q151Mc, ) were plotted as a function of dATP concentrations. 2011 PloS one Figure HIV K70Q 95 99 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. (F) The amplitudes of the burst phases from the TFV-DP reactions shown in panels C (WT, ) and D (K70Q/Q151Mc, ) were plotted as a function of TFV-DP concentrations. 2011 PloS one Figure HIV K70Q 97 101 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Antiviral activities of HIV-1s carrying mutations at residue 70 (K70R, K70G, K70E, K70T, K70N, or K70Q) in the WT (A) or Q151Mc (B) background were determined by the MAGIC5 assay. 2011 PloS one Figure HIV K70E;K70G;K70N;K70Q;K70R;K70T 77;71;89;98;65;83 81;75;93;102;69;87 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Effects of RT mutations K70Q, Q151Mc, or K70Q/Q151Mc on DNA primer extension activity and on ATP-based excision activities. 2011 PloS one Figure HIV K70Q;K70Q 24;41 28;45 RT 11 13 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Formation of extended primer products in the reactions with WT RT and K70Q/Q151Mc RT were measured at 5 ms to 5 s time points, using the following dATP concentrations: 0.5 , 1 , 2.5 , 5 (*), 10 , 20 , 50 and 75 microM (+). 2011 PloS one Figure HIV K70Q 70 74 RT;RT 63;82 65;84 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Incorporation of TFV was measured at 0.1-10 s reactions and at the following TFV-DP concentrations: 0.75 , 1.5 , 3.75 , 7.5 (*), 15 , 37.5 and 75 microM (+) for reactions with WT RT (panel C), and 1.5 , 7.5 (*), 15 , 37.5 , 55 , 75 (+), 112.5 , 150 and 200 microM (x) for reactions with K70Q/Q151Mc RT (panel D). 2011 PloS one Figure HIV K70Q 289 293 RT;RT 180;301 182;303 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Pre-steady state kinetics of incorporation of dATP or TFV-DP by WT and K70Q/Q151Mc HIV-1 RTs. 2011 PloS one Figure HIV K70Q 71 75 RT 89 92 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Rescue products (WT , K70Q , Q151Mc and K70Q/Q151Mc ) were analyzed at indicated time points. 2011 PloS one Figure HIV K70Q;K70Q 22;41 26;45 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Single-nucleotide incorporation of dATP (panels A, B, and E) or TFV-DP (panels C, D, and F) by WT (panels A, C, E, and F) and K70Q/Q151Mc (panels B, D, E, and F). 2011 PloS one Figure HIV K70Q 126 130 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Stereo view of TFV-DP in the polymerase active site of WT RT and K70Q/Q151Mc RT. 2011 PloS one Figure HIV K70Q 65 69 Pol;RT;RT 29;58;77 39;60;79 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. WT RT residues are shown as cyan sticks, K70Q/Q151Mc RT residues are shown as purple sticks. 2011 PloS one Figure HIV K70Q 41 45 RT;RT 3;53 5;55 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. A significant decrease in the reversion was observed with K65R+L74I viruses in comparison to K65R+L74V viruses. 2011 Virology journal Figure HIV K65R;K65R;L74I;L74V 58;93;63;98 62;97;67;102 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. At higher MOIs (0.01 and 0.1), measurable RT activity (B and C) or antigen p24 (D) was observed after day 10 in viruses with K65R+L74V mutation. 2011 Virology journal Figure HIV K65R;L74V 125;130 129;134 p24;RT 75;42 78;44 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Comparison of R K reversion dynamics at RT codon 65 for K65R+L74V and K65R+L74I viruses by direct and population sequencing. 2011 Virology journal Figure HIV K65R;K65R;L74I;L74V 56;70;75;61 60;74;79;65 RT 40 42 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Demonstration of increased processivity of RTs containing K65R+L74I. 2011 Virology journal Figure HIV K65R;L74I 58;63 62;67 RT 43 46 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Efficient replication of viruses containing K65R+L74I mutations in MT-2 cells. 2011 Virology journal Figure HIV K65R;L74I 44;49 48;53 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In actual autoradiograph, we were able to observe the largest cDNA bands of 72 nt, 48 nt and 54 nt in length for WT, K65R+L74V, and K65R+L74I respectively. 2011 Virology journal Figure HIV K65R;K65R;L74I;L74V 117;132;137;122 121;136;141;126 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. L I but not L V change at RT codon 74 results in a replication competent virus in the background of K65R mutation. 2011 Virology journal Figure HIV K65R 100 104 RT 26 28 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Quantification of cDNA bands synthesized by WT, K65R+L74V and K65R+L74I RTs. 2011 Virology journal Figure HIV K65R;K65R;L74I;L74V 48;62;67;53 52;66;71;57 RT 72 75 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Reversion data shows that the RT containing isoleucine change at RT codon 74 is much more stable than that with valine change in the background of K65R mutation. 2011 Virology journal Figure HIV K65R 147 151 RT;RT 30;65 32;67 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. RT containing K65R+L74I mutation showed a significant increase in the density of cDNA bands (13-36) in comparison to K65R+L74V RT. 2011 Virology journal Figure HIV K65R;K65R;L74I;L74V 14;117;19;122 18;121;23;126 RT;RT 0;127 2;129 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The autoradiograph shows increased intensities of cDNA bands (13-36) synthesized with 4 and 6 mul of RT lysates of K65R+L74I viruses in comparison to K65R+L74V RT lysates (see Figure 6). 2011 Virology journal Figure HIV K65R;K65R;L74I;L74V 115;150;120;155 119;154;124;159 RT;RT 101;160 103;162 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The graph shows a more profound difference in replication kinetics of K65R+L74I versus K65R+L74V viruses in MT-2 cells in comparison to that observed in PBM cells. 2011 Virology journal Figure HIV K65R;K65R;L74I;L74V 70;87;75;92 74;91;79;96 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The plot shows efficient replication with a sigmoid growth curve for K65R+L74I virus suggesting the yield of a replication competent virus. 2011 Virology journal Figure HIV K65R;L74I 69;74 73;78 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Viruses with K65R+L74V mutant virus did not show measurable RT activity until day 14 at 0.001 MOI. 2011 Virology journal Figure HIV K65R;L74V 13;18 17;22 RT 60 62 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. (A) SupT1 cells infected with WT or V38E virus were stained with anti-p24 Ab to detect virus infection and ZVAD-FITC to detect apoptosis induction on days 3 and 5 post infection. 2011 Virology journal Figure HIV V38E 36 40 p24 70 73 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. (C) Sequence analysis of proviral gp41 from WT and V38E infected mice. 2011 Virology journal Figure HIV V38E 51 55 gp41 34 38 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. (F) TZMbl cells were infected with either WT or V38E virus in the presence of indicated concentration of Enfuvirtide. 2011 Virology journal Figure HIV V38E 48 52 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Bystander apoptosis is induced by WT, but not V38E mutant virus infection in vitro. 2011 Virology journal Figure HIV V38E 46 50 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. CCR5 upregulation is seen on CD8 cells in both WT and V38E mutant infected mice. 2011 Virology journal Figure HIV V38E 54 58 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. CD4 decline correlates with CD8 immune activation in WT mice but not V38E mutant. 2011 Virology journal Figure HIV V38E 69 73 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Correlation between HLADR expression on CD8 cells and CD4 decline for WT (A) and V38E (B) is shown. 2011 Virology journal Figure HIV V38E 81 85 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Correlation of HLADR or PD-1 expression on CD8 cells with CD4 decline in WT and V38E infected groups was determined using Pearson's correlation coefficient. 2011 Virology journal Figure HIV V38E 80 84 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Enlarged images (right most) from A and B show the presence of apoptotic cells in close proximity to infected cells in WT, but not V38E infected mice. 2011 Virology journal Figure HIV V38E 131 135 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Immune activation is seen in the CD8+ T cells from both WT and V38E infected mice. 2011 Virology journal Figure HIV V38E 63 67 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Individual channels and merge images for WT (A) and V38E mutant (B) infected mice spleens are shown. 2011 Virology journal Figure HIV V38E 52 56 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Representative histograms of CCR5 expression in CD8 or CD4 cells in PBMCs (A) or Spleen (B) is shown for both WT and V38E Mutant. 2011 Virology journal Figure HIV V38E 117 121 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Similarly the correlation between PD-1 expression on CD8 cells and CD4 decline in WT (C) and V38E (D) was also determined. 2011 Virology journal Figure HIV V38E 93 97 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Subsequently the cells were infected with equal RT units of either WT or V38E virus or mock infected and followed for virus replication by determining the RT activity in culture supernatants. 2011 Virology journal Figure HIV V38E 73 77 RT;RT 48;155 50;157 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. V38E mutant fails to induce bystander apoptosis in vivo. 2011 Virology journal Figure HIV V38E 0 4 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. V38E mutant replicates in Mice without reverting to WT. 2011 Virology journal Figure HIV V38E 0 4 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. V38E mutant, compared to WT virus, is limited in inducing CD4 cell decline in the presence of similar levels of virus replication. 2011 Virology journal Figure HIV V38E 0 4 21276267 Interplay between HIV entry and transportin-SR2 dependency. (A) HeLaP4 cells depleted of TRN-SR2 (siTRN-SR_2) and control cells (mock and siTRN-SR_2MM) were challenged using 3 dilutions of VSV-G pseudotyped HIV-1 NL4-3 (WT) or (B) HIV-1 NL4-3 N74D CA mutant (N74D) luciferase reporter viruses. 2011 Retrovirology Figure HIV N74D 199 203 Capsid 188 190 21276267 Interplay between HIV entry and transportin-SR2 dependency. (A) shTR3, shTR4 and shSCR HeLaP4 cells were challenged using 3 dilutions of VSV-G pseudotyped HIV-1 NL4-3 (WT) or (B) HIV-1 NL4-3 N74D CA mutant (N74D) luciferase reporter viruses. 2011 Retrovirology Figure HIV N74D 147 151 Capsid 136 138 21276267 Interplay between HIV entry and transportin-SR2 dependency. (C) Same as in (A), but 2 dilutions of multiple-round viruses HIV-1 NL4-3 (WT) or (D) HIV-1 NL4-3 N74D CA mutant (N74D) carrying the HIV-1 envelope were used in the presence of 5 muM ritonavir to ensure single round infection. 2011 Retrovirology Figure HIV N74D 114 118 Env;Capsid 139;103 147;105 21276267 Interplay between HIV entry and transportin-SR2 dependency. (C) Same as in (A), but multiple-round viruses HIV-1 NL4-3 (WT) or (D) HIV-1 NL4-3 N74D CA mutant (N74D) carrying the HIV-1 envelope were used for infections. 2011 Retrovirology Figure HIV N74D 99 103 Env;Capsid 124;88 132;90 21276267 Interplay between HIV entry and transportin-SR2 dependency. (D) Stably TRN-SR2 depleted cells and control cells were infected with 6 x 104 pg p24 of infectious HIV NL4-3 (WT) or HIV-1 NL4-3 N74D CA mutant virus (N74D). 2011 Retrovirology Figure HIV N74D 152 156 p24;Capsid 82;135 85;137 21276267 Interplay between HIV entry and transportin-SR2 dependency. HeLaP4 cells depleted of TRN-SR2 (siTRN-SR_2) and control cells (mock and siTRN-SR_2MM) were challenged using 3 dilutions of pseudotyped HIV-1 NL4-3 (WT) or HIV-1 NL4-3 N74D CA mutant (N74D) luciferase reporter viruses. 2011 Retrovirology Figure HIV N74D 185 189 Capsid 174 176 21276267 Interplay between HIV entry and transportin-SR2 dependency. Stable TRN-SR2 depletion inhibits multiple round infection by HIV-1 WT and N74D CA mutant virus. 2011 Retrovirology Figure HIV N74D 75 79 Capsid 80 82 21276267 Interplay between HIV entry and transportin-SR2 dependency. Stable TRN-SR2 depletion inhibits single round infection by HIV-1 WT and N74D CA mutant virus. 2011 Retrovirology Figure HIV N74D 73 77 Capsid 78 80 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Panel B: RC change in viruses reverting M184V to wild-type between baseline and 2 months of Structured Treatment Interruption. 2011 PloS one Figure HIV M184V 40 45 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The RC change is calculated as the difference in RC between baseline and 2 month for each virus showing M184V at baseline. 2011 PloS one Figure HIV M184V 104 109 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Group B (ATV and/or SQV plus LPV or APV containing treatment) show a higher long-term success rate after 96 weeks of follow-up therapy in comparison to group A (ATV and or SQV without L76V-selecting drug). 2011 AIDS research and therapy Figure HIV L76V 184 188 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Resensitizing effects of the L76V mutation are visible in phenotype results: Phenotypic resistance analysis before and after manifestation of L76V in two representative patients (A+B). 2011 AIDS research and therapy Figure HIV L76V;L76V 29;142 33;146 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. (A) 293T cells were cotransfected with HIV-1DeltaPTAP or HIV-1DeltaPTAP/S40F and increasing amount of ALIX plasmid. 2011 Retrovirology Figure HIV S40F 72 76 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. (A) Electron micrographs showing thin sections of HeLa SS6 derived extra cellular particles of HIV-1NL-43 wt, the S40F mutant, the CA-SP1 Gag cleavage deficient mutant CA5, and the ALIX binding site mutant DeltaYP. 2011 Retrovirology Figure HIV S40F 114 118 SP1;Gag;Capsid;Capsid 134;138;131;168 137;141;133;170 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. (A) Phosphorimages of SDS-PAGE gels of immunoprecipitations of 35S pulse-chase-labeled Gag protein immunoprecipitates are presented for cell and viral lysates from HeLa cells transiently transfected with either pNLenv or pNLenv S40F. 2011 Retrovirology Figure HIV S40F 228 232 Gag 87 90 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. (B) Overexpression of ALIX does not rescue infectivity of the S40F mutant. 2011 Retrovirology Figure HIV S40F 62 66 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. (C) Specific infectivity of HIV-1NL4-3 wt and S40F mutant in combination with the A1V mutation. 2011 Retrovirology Figure HIV A1V;S40F 82;46 85;50 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. 1: HIV-1 contransfected with the empty control vector, 2: HIV-1 cotransfected with a FLAG-ALIX expression plasmid, 3: HIV-1S40F cotransfected with the empty control vector, 2: HIV-1S40F cotransfected with a FLAG-ALIX expression plasmid. 2011 Retrovirology Figure HIV S40F;S40F 123;181 127;185 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Analysis of Gag processing products and Env incorporation in wt HIV-1 and S40F mutant virions. 2011 Retrovirology Figure HIV S40F 74 78 Env;Gag 40;12 43;15 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Replication of HIV-1NL4-3 wt and S40F mutant in CEMs and HLAC. 2011 Retrovirology Figure HIV S40F 33 37 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Rescue of CA maturation by A1V mutation in CA-SP1 cleavage site. 2011 Retrovirology Figure HIV A1V 27 30 SP1;Capsid;Capsid 46;10;43 49;12;45 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. S40F mutation has no effect on ALIX mediated virus release. 2011 Retrovirology Figure HIV S40F 0 4 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. TZM-bl cells were infected with virions derived from pNL4-3 wt and S40F in combination with SP1 A1V and infectious titers were determined by measurement of the beta-galactosidase activity (RLU: relative light units). 2011 Retrovirology Figure HIV A1V;S40F 96;67 99;71 SP1 92 95 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. VLPs derived from 293T cells transfected with pDeltaR and pDeltaRS40F in combination with the A1V mutation in SP1 were purified and analyzed by Western blot using antibodies against CA. 2011 Retrovirology Figure HIV A1V 94 97 SP1;Capsid 110;182 113;184 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. VLPs produced in 293T cells transiently transfected with pDeltaR and pDeltaR S40F were purified and analyzed by Western blot using antibodies against Gag and Env. 2011 Retrovirology Figure HIV S40F 77 81 Env;Gag 158;150 161;153 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. For clarity, the dose-response curves are shown in separate panels for the R14/S chimera (A), and for the mutants containing either the V535M change only (B), or the complete set of gp41 changes of Pattern-I (C) or Pattern-II (D). 2011 Virology Figure HIV V535M 136 141 gp41 182 186 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. For clarity, the dose-response curves are shown in separate panels for the R14/S chimera (A), and the mutants harboring either the V535M change only (B), or the complete set of gp41 changes of Pattern I (C), or Pattern II (D). 2011 Virology Figure HIV V535M 131 136 gp41 177 181 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Replication of the VCV-sensitive clone S, the weakly resistant R14/S chimera, and the VCV-resistant viruses R14 and R14/S+(G514V, V535M) was determined in PBMC from CCR5 wild type and CCR5-Delta32/Delta32 homozygous donors in the presence and absence of the CXCR4-specific inhibitor AMD3465 (500 nM). 2011 Virology Figure HIV G514V;V535M 123;130 128;135 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Ten clones (one of gp41 Pattern-I and nine of gp41 Pattern-II, two of which contained only the H308P substitution) were excluded from the analysis since they contained premature stop codons and were presumably non-infectious (data not shown). 2011 Virology Figure HIV H308P 95 100 gp41;gp41 19;46 23;50 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. (A) Amino acids at the pseudo three-fold axis in the molecular model of the tubular CA assemblies were used to guide cysteine mutagenesis (P207C/T216C) for cross-linking of CA tubes. 2011 PLoS pathogens Figure HIV P207C;T216C 139;145 144;150 Capsid;Capsid 84;173 86;175 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. (A&B) Low-dose projection images of purified mutant A14C/E45C cores (11 microg/ml) incubated with human (A) or rhesus (B) TRIM5alpha CC-SPRY (18 microM). 2011 PLoS pathogens Figure HIV A14C;E45C 52;57 56;61 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. (B) Non-reducing SDS-PAGE analysis of TRIM5alpharh CC-SPRY (18 microM) binding to cross-linked P207C/T216C CA tubes (left) and cross-linking of P207C/T216C CA tubes after TRIM5alpharh CC-SPRY (18 microM) binding (right), visualized by Coomassie Blue staining. 2011 PLoS pathogens Figure HIV P207C;P207C;T216C;T216C 95;144;101;150 100;149;106;155 Capsid;Capsid 107;156 109;158 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. (C&D) CryoEM analysis of the structural effect of TRIM5alpharh CC-SPRY binding to P207C/T216C CA tubes without (C, corresponding sample in panel B, lane2) and with cross-linking (D, corresponding sample in panel B, lane4). 2011 PLoS pathogens Figure HIV P207C;T216C 82;88 87;93 Capsid 94 96 21455494 Rhesus TRIM5alpha disrupts the HIV-1 capsid at the inter-hexamer interfaces. (D&E) Representative low-dose projection images of purified P207C/T216C cores, incubated with rhesus TRIM5alpha CC-SPRY (18 microM), without (D) and with (E) oxidation for cross-linking. 2011 PLoS pathogens Figure HIV P207C;T216C 60;66 65;71 21569500 Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. CEMx174 lymphocytes were infected by co-culture with HIV-1NL4-3, HIV-1NL4-3 DeltaVV that contains a premature stop codon in vif and frameshift in vpr, or HIV-1NL4-3 RSS that contains the K51A substitution that eliminates Tat RSS activity. 2011 Retrovirology Figure HIV K51A 187 191 Vif;Vpr;Tat 124;146;221 127;149;224 21569500 Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. Host miRNA expression levels were compared between HIV-1NL4-3, Vif/Vpr-deficient or Tat K51A RSS-deficient strains. 2011 Retrovirology Figure HIV K51A 88 92 Vif;Vpr;Tat 63;67;84 66;70;87 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The dot plot panels are separated into two series for analysis: (1) those containing the WT Y712 motif in the top row, and (2) those containing the Y712C motif in the bottom row. 2011 Retrovirology Figure HIV Y712C 148 153 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The glycoproteins are separated by those containing the WT Y712 motif and by those containing the Y712C mutation. 2011 Retrovirology Figure HIV Y712C 98 103 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. (A) Graphical representation of K65R-containing transcript production with primers already harboring the mutagenic nt. 2011 PloS one Figure HIV K65R 32 36 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. (A) Outline of the reverse-transcription process in subtype B HIV-1 leading to either wild-type or K65R-containing transcripts. 2011 PloS one Figure HIV K65R 99 103 RT 19 40 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. (B) Outline of the reverse-transcription process in subtype C HIV-1 leading to either wild-type or K65R-containing transcripts. 2011 PloS one Figure HIV K65R 99 103 RT 19 40 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. (C) Graphical representation of K65R-containing transcript production with dGTP incorporation at the site of K65R development. 2011 PloS one Figure HIV K65R;K65R 32;109 36;113 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. (D) Schematic of the dislocation without realignment (P+1nt) and the dislocation with realignment or misincorporation without dislocation (P+2nt) products during dGTP incorporation at the site of K65R development. 2011 PloS one Figure HIV K65R 196 200 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Dislocation products are only observed when G is included on the primer strand yielding K65R-containing transcripts. 2011 PloS one Figure HIV K65R 88 92 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Highlighted in a square is the base that, once mutated, gives rise to the K65R drug resistance mutation. 2011 PloS one Figure HIV K65R 74 78 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. K65K, K65T and K65I production as a result of DNA synthesis with primers containing the three nt alternatives and their impact on dislocation. 2011 PloS one Figure HIV K65I;K65T;K65K 15;6;0 19;10;4 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. K65R production rates with subtype B RT on subtype B and C templates with primers containing the mutagenic nt. 2011 PloS one Figure HIV K65R 0 4 RT 37 39 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. K65R production rates with subtype C RT on subtype B and C templates with primers containing the mutagenic nt. 2011 PloS one Figure HIV K65R 0 4 RT 37 39 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Left: K65R production with subtype B RT on the subtype C template. 2011 PloS one Figure HIV K65R 6 10 RT 37 39 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Right: K65R production with subtype C RT on the subtype C template. 2011 PloS one Figure HIV K65R 7 11 RT 38 40 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Schematic of dislocation mutagenesis and the development of the K65R mutation in subtype C HIV-1. 2011 PloS one Figure HIV K65R 64 68 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Single incorrect nt incorporation and K65R production rates with subtype B RT on subtype B and C templates. 2011 PloS one Figure HIV K65R 38 42 RT 75 77 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Single incorrect nt incorporation and K65R production rates with subtype C RT on subtype B and C templates. 2011 PloS one Figure HIV K65R 38 42 RT 75 77 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Step 1: DNA synthesis approaches the end of a homopolymeric nt stretch that ends precisely at the location of K65R development. 2011 PloS one Figure HIV K65R;K65R 111;110 115;114 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The homopolymeric regions are underlined and the base responsible for the K65R mutation is indicated in bold. 2011 PloS one Figure HIV K65R 74 78 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The homopolymeric regions of both templates are underlined and the base responsible for the K65R generation is bolded. 2011 PloS one Figure HIV K65R 92 96 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The homopolymeric regions of both templates are underlined and the base responsible for the K65R mutation is indicated in bold. 2011 PloS one Figure HIV K65R 92 96 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The K65R mutation results from an AAA-to-AGA mutation in subtype B HIV-1. 2011 PloS one Figure HIV K65R 4 8 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The K65R mutation results from an AAG-to-AGG mutation in subtype C HIV-1. 2011 PloS one Figure HIV K65R 4 8 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The primers contain a G base at their 3'-end that becomes mismatched on the T on the template strand thus yielding K65R-containing transcripts. 2011 PloS one Figure HIV K65R 115 119 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The values indicated with an asterisk have a p-value <0.05 when the amount of K65R-production between both subtypes at the given time-point is compared. 2011 PloS one Figure HIV K65R 78 82 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. This series of events yields the AAG-to-AGG change that is responsible for the more facilitated appearance of the K65R mutation in subtype C HIV-1. 2011 PloS one Figure HIV K65R 114 118 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. When A is present at the 3'-end of the primer strand, it correctly binds with the T of the template strand to yield wild-type K65K-containing transcripts. 2011 PloS one Figure HIV K65K 126 130 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. When C is present at the 3'-end of the primer strand, it incorrectly binds with the T of the template strand to yield K65T-containing transcripts. 2011 PloS one Figure HIV K65T 118 122 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. When T is present at the 3'-end of the primer strand, it incorrectly binds with the T of the template strand to yield K65I-containing transcripts. 2011 PloS one Figure HIV K65I 118 122 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Correlation between K103N mutants quantified by allele-specific real-time PCR and ultra-deep pyrosequencing. 2011 PloS one Figure HIV K103N 20 25 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Detection threshold of ultra-deep pyrosequencing for detecting minor K103N variants in function of the read number. 2011 PloS one Figure HIV K103N 69 74 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Frequencies of K103N mutants. 2011 PloS one Figure HIV K103N 15 20 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Higher efavirenz half-life in patients in whom K103N emerged than in whom it did not. 2011 PloS one Figure HIV K103N 47 52 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Measured frequencies of K103N mutants on mixtures of wild-type and K103N mutants with known proportions of K103N. 2011 PloS one Figure HIV K103N;K103N;K103N 24;67;107 29;72;112 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Number of K103N mutant copies The correlation was estimated by calculating Spearman's rank correlation coefficient for 16 samples successfully quantified by both methods for the AAC and/or AAT mutated codons. 2011 PloS one Figure HIV K103N 10 15 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Plot of the measured frequencies of K103N mutants versus the input template, assessed on four independent experiments of mixtures of wild-type and K103N mutants at various frequencies. 2011 PloS one Figure HIV K103N;K103N 36;147 41;152 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Sensitivity of the allele-specific PCR assay for detecting minor K103N mutants and reciprocal validation with ultra-deep pyrosequencing. 2011 PloS one Figure HIV K103N 65 70 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The assay detects K103N mutants down to a frequency of 0.01% in all experiments. 2011 PloS one Figure HIV K103N 18 23 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Kinetics of minority K103N and M184V HIV-1 variants in patients receiving early ART and undergoing intended treatment interruption. 2011 PloS one Figure HIV K103N;M184V 21;31 26;36 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Minority K103N (blue triangles) and M184V (red diamonds) HIV-1 variants were quantified by AS-PCR; percentages are given and were used to calculate the absolute amounts of these variants based on the viral load. 2011 PloS one Figure HIV K103N;M184V 9;36 14;41 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Percent values below the assays discriminatory abilities (0.2% for M184V and 0.01% for K103N) or the individually calculated detection limits based on the viral load are shown by less-than signs. 2011 PloS one Figure HIV K103N;M184V 87;67 92;72 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. (A) Comparison of strand transfer activity in the presence of RAL of wt (circle), G140S (square) and G140S/Q148R (triangle) mutants. 2011 Retrovirology Figure HIV G140S;G140S;Q148R 82;101;107 87;106;112 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. (B) Comparison of strand transfer activity in the presence of RAL of wt (circle), N155H (triangle), Y143C (square) and N155H/Y143C (inverted triangle) HIV-2 INs. 2011 Retrovirology Figure HIV N155H;N155H;Y143C;Y143C 82;119;100;125 87;124;105;130 IN 157 160 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. (B) Comparison of strand transfer activity in the presence of RAL of wt (N1) (circle), E92Q (square), Y143C (triangle), E92Q/Y143C (inverted triangle) and T97A/Y143C (diamond) mutants. 2011 Retrovirology Figure HIV E92Q;E92Q;T97A;Y143C;Y143C;Y143C 87;120;155;102;125;160 91;124;159;107;130;165 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. The A182T mutation promotes a reorientation of R179 side-chain. 2011 PloS one Figure HIV A182T 4 9 21859446 Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. D, E, F) Impact of the N348I (D), N348A (E) and N348L (F) mutations on the beta14-beta15 loop in the p51 subunit of HIV-1 RT in complex with an RNA/DNA duplex that extends into the RNase H active site. 2011 Retrovirology Figure HIV N348A;N348I;N348L 34;23;48 39;28;53 RT 122 124 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. (C) Control (Scr) and Tnp3 KD HeLa cells were infected with the N74D mutant vector and analyzed by flow cytometry 24 hours later; mean values +- SD of three independent experiments are shown. 2011 PLoS pathogens Figure HIV N74D 64 68 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Note that the T54A and T54A/N57A have ~20 fold lower infectivity than wild type virus. 2011 PLoS pathogens Figure HIV N57A;T54A;T54A 28;14;23 32;18;27 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Virus input was normalized for infectivity in HeLa cells, hence the higher amount of N74D CA detected at the 6h time point. 2011 PLoS pathogens Figure HIV N74D 85 89 Capsid 90 92 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. (B) Cel 1 cleavage of the photocrosslinked complex of IN I146C. 2011 PloS one Figure HIV I146C 57 62 IN 54 56 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. (D) Y-mer DNA sequence with positions of preferred crosslinking detected by Cel1 indicated for each IN derivative by red (I146C), green (R244C) and teal (S124C) arrows; (E) 3-D model of the Y-mer DNA with positions of preferred crosslinking detected by Cel1 indicated for each IN derivative by green (C244), red (C146) and teal (C124) dots. 2011 PloS one Figure HIV I146C;R244C;S124C 122;137;154 127;142;159 IN;IN 100;277 102;279 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. A flexible loop contains the substituted residue I146C. 2011 PloS one Figure HIV I146C 49 54 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Nucleotides 3 and 8 on the host DNA are red and the substituted residue S124C is shown as sticks. 2011 PloS one Figure HIV S124C 72 77 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Panel A shows crosslinking to the C23S/C125S/E157C/F199K ASV IN derivative (labeled Cys157 after the key mutation); panel B to C23S/C125S/E157C/F199K/W259A (labeled Cys157/Ala259), and panel C to D64C/F199K (labeled Cys64). 2011 PloS one Figure HIV C125S;C125S;C23S;C23S;E157C;E157C;F199K;F199K;W259A;D64C;F199K 39;132;34;127;45;138;51;144;150;196;201 44;137;38;131;50;143;56;149;155;200;206 IN 61 63 22145019 Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Substituted catalytic residues D64C and E157C are shown in magenta. 2011 PloS one Figure HIV D64C;E157C 31;40 35;45 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. (PDB:1FGL) E, NL4.3 HIV-1 GFP vector titer on CRFK cells expressing empty vector (EV), TRIMCypA, wild type TRIMNup358, or TRIMNup358 mutant V61M. 2011 PLoS pathogens Figure HIV V61M 140 144 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. B, HeLa cells expressing scrambled control (SC), or Nup358 specific shRNA were transiently transduced with either MLV empty vector control or vector expressing CypA specific shRNA and subsequently infected with wild type NL4.3 HIV-1 GFP vector or CA mutant P90A or O-group MVP5180 GFP vector. 2011 PLoS pathogens Figure HIV P90A 257 261 Capsid 247 249 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. C, HIV-1 capsid mutants that are less sensitive to Nup358, Nup153 or TRN-SR2 RNAi (HIV-1 CA N57A or N74D) enter the nucleus through a different pathway that directs their integration into genome areas of lower density of transcription units. 2011 PLoS pathogens Figure HIV N57A;N74D 92;100 96;104 Capsid;Capsid 9;89 15;91 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. D, Depletion of Nup358 by RNAi reduces viral nuclear entry via the Nup358-dependent pathway and the virus gains access via an Nup358-independent alternative pathway resulting in phenotypically similar integration site selection as observed for the CA mutants N74D or N57A. 2011 PLoS pathogens Figure HIV N57A;N74D 267;259 271;263 Capsid 248 250 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. E, Time course of replication competent NL4.3 (Ba-L Env) bearing wild type, P90A or N74D CA in HeLa TZM-bl cells. 2011 PLoS pathogens Figure HIV N74D;P90A 84;76 88;80 Env;Capsid 52;89 55;91 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. F, Replication assay of NL4.3 (Ba-L Env) bearing wild type or CA mutants P90A or N74D in human MDM. 2011 PLoS pathogens Figure HIV N74D;P90A 81;73 85;77 Env;Capsid 36;62 39;64 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. SEC profiles of IN mutants W131A, Q168L, K188Q, Y194E and Y194F are shown in red, green, orange, cyan and purple, respectively. 2011 Retrovirology Figure HIV K188Q;Q168L;W131A;Y194E;Y194F 41;34;27;48;58 46;39;32;53;63 IN 16 18 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Leu-122 of the Pro-dependent S1' subsite and Arg-148 of the Pro-independent S2'-S3' subsite of CypA are highlighted in green. 2011 BMC structural biology Figure HIV P122L;P148R 0;45 18;63 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Mutation of Arg-80 with Ala does not influence the secondary structure of Vpr75-90. 2011 BMC structural biology Figure HIV R80A 12 27 Vpr 74 77 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. SPR sensorgrams for synthetic Vpr75-90, the mutants Vpr75-90 (R76Q, V83I, T84I), Vpr75-90 (R76Q, V83I, R80A, T84I), Vpr75-90 (R80A) and the shorter peptides Vpr69-78, Vpr75-84, Vpr81-90 and Vpr87-96 were analyzed for binding to immobilized recombinant CypA. 2011 BMC structural biology Figure HIV R76Q;R76Q;R80A;R80A;T84I;T84I;V83I;V83I 62;91;103;126;74;109;68;97 66;95;107;130;78;113;72;101 Vpr;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr;Vpr 30;52;81;116;157;167;177;190 33;55;84;119;160;170;180;193 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Baseline samples (white boxes) and V38A mutant clones (gray boxes). 2012 Retrovirology Figure HIV V38A 35 39 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Baseline samples (white boxes) and V38A samples (gray boxes). 2012 Retrovirology Figure HIV V38A 35 39 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Env expression was determined by the percentage of Env-positive cells in an inter-patient analysis using the clones constructed from each patient or in an intra-patient analysis using clones constructed from baseline and after treatment (V38A) samples (A). 2012 Retrovirology Figure HIV V38A 238 242 Env;Env 0;51 3;54 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. Env-expressing plasmids constructed from three patients carrying an amino acid N, T or I at position 140 with (V38A) without substitutions at position 38 of gp41 were transfected into HeLa cells. 2012 Retrovirology Figure HIV V38A 111 115 gp41;Env 157;0 161;3 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. The alignment of the gp41 ectodomain sequence (HR1 and HR2 domains) from the selected recombinant plasmids derived from three patients who failed an ENF-based treatment and carried a V38A mutation (HR1 box) with the amino acid I, N or T at position 140 (HR2 box). 2012 Retrovirology Figure HIV V38A 183 187 gp41 21 25 22333046 The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype. The median values obtained from the clones constructed from samples from each patient were compared in an inter-patient analysis, and those obtained from baseline (white boxes) and after treatment samples with the change V38A (gray boxes) clones were also compared in an intra-patient analysis using a nonparametric Mann Whitney test. 2012 Retrovirology Figure HIV V38A 221 225 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. ATP-mediated AZT-MP excision activity and RNase H activity of wildtype, A360V, TAM-1 and TAM-1/A360V HIV-1 RT. 2012 PloS one Figure HIV A360V;A360V 95;72 100;77 RT 107 109 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Reaction times were: wildtype and A360V = 10, 20, 30, 45, 60, 75, 90, 105 min; TAM-1 and TAM-1/A360V = 3, 7.5, 15, 25, 35, 45, 60, 75 min. 2012 PloS one Figure HIV A360V;A360V 95;34 100;39 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Reaction times were: wildtype and A360V = 15, 30, 45, 60, 75, 90, 105, 120 min; TAM-1 and TAM-1/A360V = 3, 7.5, 15, 25, 35, 45, 60, 75 min. 2012 PloS one Figure HIV A360V;A360V 96;34 101;39 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The reaction times were wildtype and A360V = 15, 30, 45, 60, 75, 90, 105, 120 min; TAM-1 and TAM-1/A360V = 3, 7.5, 15, 25, 35, 45, 60, 75 min. 2012 PloS one Figure HIV A360V;A360V 99;37 104;42 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Amide chemical shift differences between the wild type and E45A, E45A/R132T and P38A mutant CA-NTD proteins. 2012 Retrovirology Figure HIV E45A;E45A;P38A;R132T 59;65;80;70 63;69;84;75 Capsid 92 94 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Combined 1H, 15 N chemical shift differences between wild-type and mutants E45A (A), E45A/R132T (B) and P38A (C) are plotted versus residue number. 2012 Retrovirology Figure HIV E45A;E45A;P38A;R132T 75;85;104;90 79;89;108;95 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Inhibition of wild type, E45A, and E45A/R132T mutant HIV-1 by PF74. 2012 Retrovirology Figure HIV E45A;E45A;R132T 25;35;40 29;39;45 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Rescue of P38A (A) and E45A (B) mutants by second-site mutations T216I and R132T, respectively. 2012 Retrovirology Figure HIV E45A;P38A;R132T;T216I 23;10;75;65 27;14;80;70 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Rescue of P38A and E45A infectivity defects mutations by second-site mutations T216I and R132T. 2012 Retrovirology Figure HIV E45A;P38A;R132T;T216I 19;10;89;79 23;14;94;84 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Second-site suppressor mutation R132T relieves the cell-cycle dependence of the E45A mutant in a single-cycle infectivity assay. 2012 Retrovirology Figure HIV E45A;R132T 80;32 84;37 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The second-site mutation T216I restores the ability of P38A particles to saturate TRIM5 restrictions in simian cells. 2012 Retrovirology Figure HIV P38A;T216I 55;25 59;30 22530020 Counteraction of tetherin antiviral activity by two closely related SIVs differing by the presence of a Vpu gene. Amino acid substitutions were introduced into full-length human tetherin: (A) P40L, (B) T45I, (C) P40L+T45I. 2012 PloS one Figure HIV P40L;P40L;T45I;T45I 76;96;86;103 82;102;92;107 22530020 Counteraction of tetherin antiviral activity by two closely related SIVs differing by the presence of a Vpu gene. neglectus (W17C) (D) tetherin. 2012 PloS one Figure HIV W17C 11 15 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. (A) Mutations H105Y, V255M, S375R/N, G471R and D474N were introduced in the SF162 envelope by site-directed mutagenesis and subsequently cloned into a full -length pBRNL4.3 plasmid, generating replication competent virus. 2012 Retrovirology Figure HIV D474N;G471R;H105Y;S375N;S375R;V255M 47;37;14;28;28;21 52;42;19;35;35;26 Env 82 90 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Close-up views of both V255M and S375R mutants in interaction with M48U1. 2012 Retrovirology Figure HIV S375R;V255M 33;23 38;28 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. D474N was introduced in the BaL and SF162 background. 2012 Retrovirology Figure HIV D474N 0 5 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. pBRNL4.3 replication competent molecular clones, carrying the H105Y, S375R, S375N, G471R, and D474N mutations were tested for their sensitivity towards the miniCD4 in a TZM-bl based assay. 2012 Retrovirology Figure HIV D474N;G471R;H105Y;S375N;S375R 94;83;62;76;69 99;88;67;81;74 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The H105Y mutation is related to the rM48BaL virus; however for these experiments this mutation was also introduced in the SF162 envelope. 2012 Retrovirology Figure HIV H105Y 4 9 Env 129 137 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The H105Y mutation, found in the rM48BaL virus, was also introduced in the SF162 gp120 background. 2012 Retrovirology Figure HIV H105Y 4 9 gp120 81 86 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The S375R mutation was introduced in the envelopes of the subtype B BaL virus, the primary subtype C VI829 virus, and the primary CRF02_AG VI1090 strain and used to produce mutant pseudoviruses. 2012 Retrovirology Figure HIV S375R 4 9 Env 41 50 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. A strong response to the W61D peptide ARP7035.19 is common to both G19 and G21which is lost when the corresponding SF33 peptide ARP7117.18 is substituted. 2012 Retrovirology Figure HIV W61D 25 29 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Panel B compares the mean responses of the 4 peptides that comprise the C2 pool, with homology between W61D and IIIB, with the corresponding non-homologous SF33 peptides, individually. 2012 Retrovirology Figure HIV W61D 103 107 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. Responses to the vaccine isolate W61D peptide pools were compared to heterologous IIIB and SF33 isolates. 2012 Retrovirology Figure HIV W61D 33 37 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. The C2 pool contains peptides with homology between W61D and IIIB. 2012 Retrovirology Figure HIV W61D 52 56 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. The C3 pool contains peptides with homology between W61D and SF33. 2012 Retrovirology Figure HIV W61D 52 56 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Animals were infected with wild-type (wt) or K65R RT viral mutants as described in Table 1. 2012 Retrovirology Figure HIV K65R 45 49 RT 50 52 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Catalytic rate constants for the cleavage of D38Trna were 0.34 +- 0.15 min-1, 0.39 +- 0.18 min-1 and 1.16 +- 0.54 min-1 for WT, and mutant RTs M41L/L210W/T215Y and M41L/L210W/T215Y/R284K, respectively. 2012 Retrovirology Figure HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 148;169;143;164;181;154;175 153;174;147;168;186;159;180 RT 139 142 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. For the excision of d4TMP, the kobs values for WT and mutants R284K, M41L/L210W/T215Y, and M41L/L210W/T215Y/R284K were 3.37 x 10-3 +- 1.93 x 10-4 min-1, 2.62 x 10-3 +- 1.42 x 10-4 min-1, 3.72 x 10-2 +- 1.58 x 10-3 min-1, and 3.70 x 10-2 +- 2.29 x 10-3 min-1, respectively. 2012 Retrovirology Figure HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y;R284K 74;96;69;91;108;80;102;62 79;101;73;95;113;85;107;67 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Reactions were carried out with D38/25PGA or D38T/25PGA complexes (sequences given above). 2012 Retrovirology Figure HIV D38T 45 49 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. RNase H activity of wild-type and mutants RTs M41L/L210W/T215Y and M41L/L210W/T215Y/R284K. 2012 Retrovirology Figure HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 51;72;46;67;84;57;78 56;77;50;71;89;62;83 RT 42 45 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The calculated kobs values for the AZTMP excision reaction were 2.82 x 10-3 +- 1.48 x10-4 min-1 for WT RT, 2.42 x 10-3 +- 1.22 x 10-4 min-1 for mutant R284K RT, 4.69 x 10-2 +- 1.69 x 10-3 min-1 for M41L/L210W/T215Y RT, and 3.64 x10-2 +- 3.08 x 10-3 min-1 for M41L/L210W/T215Y/R284K RT. 2012 Retrovirology Figure HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y;R284K 203;264;198;259;276;209;270;151 208;269;202;263;281;214;275;156 RT;RT;RT;RT 103;157;215;282 105;159;217;284 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The catalytic rate constants with this substrate were 0.33 +- 0.05 min-1 for WT RT, and 0.35 +- 0.03 min-1 and 0.87 +- 0.12 min-1 for mutants M41L/L210W/T215Y and M41L/L210W/T215Y/R284K, respectively. 2012 Retrovirology Figure HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 147;168;142;163;180;153;174 152;173;146;167;185;158;179 RT 80 82 22970187 Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41. E: EC50s of IgG1 m43, CD4bs mAbs b12 and VRC01, CD4i mAb 17b, and V3 loop-specific mAb 39F with gp120JRFL wild-type (WT) and V1, V2, V3 loop deletion mutants, and gp120yu2 WT and its site mutants in CD4bs (D368R), CD4i (I420R), loop D (N279E) and V5 loop (G459E). 2012 PloS one Figure HIV D368R;G459E;I420R;N279E 206;256;220;236 211;261;225;241 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Four different combination profiles initialed with mutations A98G, V108I, Y181C and I135T with I382L were selected by NVP in CRF07_BC. 2012 PloS one Figure HIV A98G;I135T;I382L;V108I;Y181C 61;84;95;67;74 65;89;100;72;79 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. All mutations and M184V-reversals for every passage and isolate are summarized. 2012 Viruses Figure HIV M184V 18 23 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Appearance of new mutations before and after 184 Reversal: All mutations generated (diamonds) per drug setting, before (M184V, left column) and after M184V-reversal (After 184 Reversal, right column) are summarized. 2012 Viruses Figure HIV M184V;M184V 120;150 125;155 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. During drug escalation, the event of M184V-reversal is required for a mutation to appear in the right column. 2012 Viruses Figure HIV M184V 37 42 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Isolates #1-5 (represented by colored cubes) started with a priori no mutations 'MUT' and no M184V-reversal (0MUT/0REV). 2012 Viruses Figure HIV M184V 93 98 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Progression of Mutations With and Without M184V-reversal. 2012 Viruses Figure HIV M184V 42 47 23012621 Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Shaded areas within 'REV' indicate M184V-reversal. 2012 Viruses Figure HIV M184V 35 40 Rev 21 24 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. EC50 values for T97A and G140S did not statistically differ from WT for either drug. 2012 PloS one Figure HIV G140S;T97A 25;16 30;20 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Light-grey bars indicate variants that are significantly different from WT (P>0.05) and * indicates a significant difference between Q148R and G140S+Q148R HIV-2 (P>0.01) (ANOVA of log10-transformed titers with Tukey's post-test). 2012 PloS one Figure HIV G140S;Q148R;Q148R 143;133;149 148;138;154 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Panels B and D show representative dose-response data for WT, Q148R, and G140S+Q148R versus raltegravir and WT, N155H, and E92Q+N155H versus elvitegravir, respectively. 2012 PloS one Figure HIV E92Q;G140S;N155H;N155H;Q148R;Q148R 123;73;112;128;62;79 127;78;117;133;67;84 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. With the exception of Q148H versus raltegravir and Y143C versus elvitegravir, EC50 values for all strains shown in color were statistically greater than the corresponding values for wild-type ROD9 (P>0.05, ANOVA of log10-transformed EC50 values with Tukey's post-test). 2012 PloS one Figure HIV Q148H;Y143C 22;51 27;56 23049972 Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. Raltegravir-associated DRMs (A) E138A, (B) E138K, (C) G140S and (D) Q148H were detected at a higher prevalence in plasma than in PBMC. 2012 PloS one Figure HIV E138A;E138K;G140S;Q148H 30;41;52;66 37;48;59;73 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. (B) Purified CD4+ T cells were infected with the same amount (5 ng p24) of CH77 T/F virus and its mutants (TK, T242N and NIA). 2012 Retrovirology Figure HIV T242N 111 116 p24 67 70 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. (C) Comparison of frequencies of the recombinant virus and other three viruses (T/F, T242N and NIA) in the same sample determined by PASS (596 genomes) and SGA sequencing (47 genomes). 2012 Retrovirology Figure HIV T242N 85 90 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. (C) Frequencies of the viruses with I64T and/or R355K mutations at screening and later time points were determined by SGA . 2012 Retrovirology Figure HIV I64T;R355K 36;48 40;53 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Relative fitness was determined for (A) T/F versus T242N (sij = -0.42 +- 0.03), (B) T242N versus NIA (sij = 0.37 +- 0.14), (C) T/F versus NIA (sij = -0.03 +- 0.03), and (D) T/F versus TK (sij = 0.05 +- 0.02). 2012 Retrovirology Figure HIV T242N;T242N 51;82 56;89 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Relative fitness was determined for (A) T/F versus T242N (sij = 0.009 +- 0.007), (B) T/F versus NIA (sij = 0.02 +- 0.02), (C) NIA versus T242N (sij = 0.05 +- 0.04) and (D) T/F versus TK viruses (sij = 0.01 +- 0.01). 2012 Retrovirology Figure HIV T242N;T242N 51;137 56;142 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The T/F virus (arrow 1) has 242T (green) and 247V (green); the T242N virus (arrow 2) has 242N (red) and 247V (green); the NIA virus has (arrow 3) has 242N (red) and 247I (red); and the recombinant (rec; arrow 4) has 242T (green) and 247I (red). 2012 Retrovirology Figure HIV T242N 63 68 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The three parental viruses (T/F, T242N and NIA) are indicated by thicker lines at the top. 2012 Retrovirology Figure HIV T242N 33 38 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The TK virus contains both I62T and R355K mutations. 2012 Retrovirology Figure HIV I62T;R355K 27;36 31;41 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The TW10 CTL epitope region (indicated by a red box) was enlarged to better show the nucleotide identities at three sites (T242N, V247I and G248A) in the viral population (right panel). 2012 Retrovirology Figure HIV G248A;T242N;V247I 140;123;130 145;128;135 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Three viruses (T/F, T242N and NIA) were co-cultured and passaged six times. 2012 Retrovirology Figure HIV T242N 20 25 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Two recombinants (viruses with I64T or R355K mutation) were detected by linkage analysis of mutations at positions 64 in Tat and 355 in Env. 2012 Retrovirology Figure HIV I64T;R355K 31;39 35;44 Tat;Env 121;136 124;139 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. M41L, L210W, and T215Y mutations are indicative of the TAM-1 pathway; D67N/G, K70R, T215F, and K219Q/E/R mutations are indicative of the TAM-2 pathway. 2012 Journal of the International AIDS Society Figure HIV D67G;D67N;K219E;K219Q;K219R;K70R;L210W;T215F;T215Y;M41L 70;70;95;95;95;78;6;84;17;0 76;76;104;104;104;82;11;89;22;4 23308067 Human tetherin exerts strong selection pressure on the HIV-1 group N Vpu protein. (C) HIV-1 N Vpus also evolved the capability to interact efficiently with HU tetherin after zoonotic transmission and the residues in the TMD involved in this interaction (E15A, V19A and IV25/26LL) are highly conserved (11/11). 2012 PLoS pathogens Figure HIV E15A;V19A 172;178 176;182 Vpu 12 16 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Dendrograms obtained from average linkage hierarchical agglomerative clustering, showing significant clusters of L76V protease inhibitors resistance mutations among B subtype sequences (A), and among "non-B" subtype sequences (B). 2013 PloS one Figure HIV L76V 113 117 PR 118 126 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Prevalence of the L76V mutation between 1998 and 2010 in a database containing 29,643 sequences issued from clinical samples with any antiretroviral drug resistance. 2013 PloS one Figure HIV L76V 18 22 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Proportion of protease inhibitors resistance-associated mutations with the L76V mutation in HIV-1 subtype B samples and in HIV-1 "non-B" samples. 2013 PloS one Figure HIV L76V 75 79 PR 14 22 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. (B) Infection of U87.CD4.CCR5 and U87.CD4.CXCR4 indicator cells with pseudovirions bearing S11R, D25K or WT V3 sequences. 2013 Retrovirology Figure HIV D25K;S11R 97;91 101;95 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. (A) pNL4.3IN(WT), pNL4.3IN(H51Y), pNL4.3IN(R263K), and pNL4.3IN(H51Y/R263K) infectivity were measured by quantifying luciferase activity in relative luminescent units (RLU) produced by TZM-bl cells infected with increasing concentrations of virus (in ng of p24 antigen). 2013 Retrovirology Figure HIV H51Y;H51Y;R263K;R263K 27;64;43;69 31;68;48;74 p24 257 260 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. (A) Recombinant integrase proteins INWT, INH51Y, INR263K, and INH51Y/R263K were purified (lanes 2 to 5) and (B) used to measure strand-transfer activity in relative fluorescent units (RFU/h) in the presence of 18 nM target DNA and various concentrations of purified recombinant protein. 2013 Retrovirology Figure HIV R263K 69 74 IN;IN;IN;IN 16;41;49;62 25;43;51;64 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. (B) Reverse transcriptase (RT) activity was measured as counts per minute (cpm) per day in the culture fluids of PM1 cells infected with pNL4.3IN(WT), pNL4.3IN(H51Y), pNL4.3IN(R263K), or pNL4.3IN(H51Y/R263K) virus. 2013 Retrovirology Figure HIV H51Y;H51Y;R263K;R263K 160;196;176;201 164;200;181;206 RT;RT 4;27 25;29 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Effect of the H51Y and R263K mutations on integrase structure. 2013 Retrovirology Figure HIV H51Y;R263K 14;23 18;28 IN 42 51 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Effects of the H51Y and R263K mutations on HIV infectivity and replicative fitness. 2013 Retrovirology Figure HIV H51Y;R263K 15;24 19;29 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Effects of the H51Y and R263K mutations on HIV integration. 2013 Retrovirology Figure HIV H51Y;R263K 15;24 19;29 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. INH51Y/R263K (Dark green backbone). 2013 Retrovirology Figure HIV H51Y;R263K 2;7 6;12 IN 0 2 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Integrated HIV DNA was quantified by qPCR in primary human PBMCs infected with wild-type virus and with viruses containing the H51Y, R263K, and H51Y/R263K mutations for 72h. 2013 Retrovirology Figure HIV H51Y;H51Y;R263K;R263K 127;144;133;149 131;148;138;154 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. G48W, N88G). 2013 PLoS computational biology Figure HIV N88G;G48W 6;0 10;4 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. In particular the specific profiles of V106I, Y181C and G190A are reproduced well. 2013 PLoS computational biology Figure HIV G190A;V106I;Y181C 56;39;46 61;44;51 23436985 Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. M46L, A71T, V82A, V82S) but also several novel mutations (e.g. 2013 PLoS computational biology Figure HIV A71T;V82A;V82S;M46L 6;12;18;0 10;16;22;4 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. (B) Evaluation of exchange rates for CypA catalyzed isomerisation of G89-P90 in HIV1caN and HIV1caN V86M. 2013 Retrovirology Figure HIV V86M 100 104 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. CRFK cells were transduced with R332G-R335G TRIM5alphahu or with the empty vector as control and subsequently challenged with a single dose of WT or V86M HIV-1NL-GFP in presence or absence of 2 muM CsA. 2013 Retrovirology Figure HIV R332G;R335G;V86M 32;38;149 37;43;153 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Direct correlation between the effect of mutation V86M and the effect of CsA treatment. 2013 Retrovirology Figure HIV V86M 50 54 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Exchange rates (kex) in the order of 5 s-1 for HIV1caN/CypA and 20 s-1 for HIV1caN V86M/CypA were extracted by fitting auto peaks and exchange peaks as described by Bosco et al. 2013 Retrovirology Figure HIV V86M 83 87 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Following antibiotic selection, cells were challenged with a single dose of WT or V86M HIV-1NL-GFP, in the presence or absence of 2 muM CsA. 2013 Retrovirology Figure HIV V86M 82 86 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Following antibiotic selection, cells were infected with multiple doses (A, B) or with a single dose (C) of WT or V86M HIV-1NL-GFP. 2013 Retrovirology Figure HIV V86M 114 118 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Normalised peak intensities of trans auto peaks and the corresponding exchange peaks for HIV1caN/CypA and HIV1caN V86M/CypA were plotted as a function of mixing time (s). 2013 Retrovirology Figure HIV V86M 114 118 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Note that in the case of HIV1caN V86M a broad G89cis peak and an additional cis-exchange peak indicates a second conformer. 2013 Retrovirology Figure HIV V86M 33 37 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Restriction of a spreading CA-V86M HIV-1 infection. 2013 Retrovirology Figure HIV V86M 30 34 Capsid 27 29 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Restriction of CA-V86M HIV-1 by R332G-R335G TRIM5alphahu is independent of cyclophilin A. 2013 Retrovirology Figure HIV R332G;R335G;V86M 32;38;18 37;43;22 Capsid 15 17 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Student's t-test was used to test for significance of data, specifically WT vs V86M viruses in cells expressing R332G-R335G or TRIM5alpha (p = 0.0020 and p = 0.0015, respectively). 2013 Retrovirology Figure HIV R332G;R335G;V86M 112;118;79 117;123;83 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Sup-T1 cells transduced with a control shRNA against luciferase (A) or with an shRNA targeting CypA (B) and expressing the indicated TRIM5alpha proteins were infected once with an identical dose of WT or V86M HIV-1NL4-3 normalized by RT activity. 2013 Retrovirology Figure HIV V86M 204 208 RT 234 236 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. TE671 (A), Sup-T1 (B) and CRFK (C) cells were transduced with either WT TRIM5alphahu, R332G-R335G TRIM5alphahu, or with the "empty" vector as a control. 2013 Retrovirology Figure HIV R332G;R335G 86;92 91;97 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. TE671 cells (A) and Sup-T1 cells (B) expressing R332G-R335G TRIM5alphahu or transduced with the "empty" vector were challenged with WT or V86M HIV-1NL-GFP in the presence of increasing concentrations of CsA. 2013 Retrovirology Figure HIV R332G;R335G;V86M 48;54;138 53;59;142 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. TE671 cells (A) and Sup-T1 cells (B) transduced with either WT TRIM5alphahu, R332G-R335G TRIM5alphahu or with the "empty" vector were also transduced with shRNAs targeting CypA or the non-relevant luciferase mRNAs. 2013 Retrovirology Figure HIV R332G;R335G 77;83 82;88 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. TE671 cells expressing the indicated TRIM5alpha were challenged with WT or V86M HIV-1NL-GFP. 2013 Retrovirology Figure HIV V86M 75 79 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The four panels represent backbone amide 1H,15N correlations for the preceding G89 residue in HIV1caN and in HIV1caN V86M in the presence and absence of CypA. 2013 Retrovirology Figure HIV V86M 117 121 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. The increase in HIV-1 infectivity in TE671 cells expressing the indicated TRIM5alphahu in presence of 2 muM CsA was plotted against the increase in infectivity resulting from the V86M mutation. 2013 Retrovirology Figure HIV V86M 179 183 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M CA interactions with CypA studied by NMR. 2013 Retrovirology Figure HIV V86M 0 4 Capsid 5 7 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M enhances nuclear transport of HIV-1 DNA in restrictive conditions. 2013 Retrovirology Figure HIV V86M 0 4 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M HIV-1 restriction by R332G-R335G TRIM5alphahu in cat cells is not counteracted by CsA treatment. 2013 Retrovirology Figure HIV R332G;R335G;V86M 26;32;0 31;37;4 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. V86M mutation in HIV-1 capsid confers partial resistance against R332G-R335G TRIM5alphahu. 2013 Retrovirology Figure HIV R332G;R335G;V86M 65;71;0 70;76;4 Capsid 23 29 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. WT and V86M virus preparations were adjusted by RT assay. 2013 Retrovirology Figure HIV V86M 7 11 RT 48 50 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. Major drug-resistance mutations in drug naive individuals: Red circles - K103N; Green triangle - M184V; orange rhombus - protease M46I. 2013 PloS one Figure HIV K103N;M184V;M46I 73;97;130 78;102;134 PR 121 129 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Where processing was evident the single N610Q resulted in the largest shift in apparent molecular weight of the gp41 ectodomain, an approximately 5-6 kDa loss. 2013 PloS one Figure HIV N610Q 40 45 gp41 112 116 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Wild type CM243, single mutant N610Q and N615Q were processed to gp120 and gp41 ectodomain subunits. 2013 PloS one Figure HIV N610Q;N615Q 31;41 36;46 gp120;gp41 65;75 70;79 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. The S61A mutation conferred enhanced intracellular stability. 2013 PloS one Figure HIV S61A 4 8 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). Histogram showing number of women with drug resistant HIV infection that had each of the following protease inhibitor (PI), nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations M46L, I85V, K65R, L74I, K219E, M184V, K101E, V106M, Y181C or G190A. 2013 PloS one Figure HIV G190A;I85V;K101E;K219E;K65R;L74I;M184V;M46L;V106M;Y181C 303;248;280;266;254;260;273;242;287;294 308;252;285;271;258;264;278;246;292;299 NNRTI;NRTI;PR;NNRTI;NRTI;PI 177;124;99;225;168;119 213;156;107;230;172;121 HIV infections 54 67 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. ***, P<0.001 versus K601D, 2-tailed unpaired t test assuming unequal variances. 2013 PLoS pathogens Figure HIV K601D 20 25 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. D, Utilization of CCR5 mutants in cell-cell fusion by T138N/L494I/K601N and DeltaN139INN/K601N. 2013 PLoS pathogens Figure HIV K601N;L494I;T138N;K601N 66;60;54;89 71;65;59;94 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. E, T138N and DeltaN139INN mutations on a WT Env background do not affect cell-cell fusion activity (Mean RLU +- standard error, n>3). 2013 PLoS pathogens Figure HIV T138N 3 8 Env 44 47 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. E, Utilization of the CCR5-Y14N coreceptor mutant in cell-cell fusion by T138N/L494I/K601N and DeltaN139INN/K601N. 2013 PLoS pathogens Figure HIV K601N;L494I;T138N;K601N 85;79;73;108 90;84;78;113 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Effects of T138N, DeltaN139INN and L494I mutations on gp120-gp41 association and cell-cell fusion activities of DSR mutants. 2013 PLoS pathogens Figure HIV L494I;T138N 35;11 40;16 gp120;gp41 54;60 59;64 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. F, Sensitivity of T138N/L494I/K601N and DeltaN139INN/K601N to the fusion inhibitor peptide, C34. 2013 PLoS pathogens Figure HIV K601N;L494I;T138N;K601N 30;24;18;53 35;29;23;58 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. F, T138N and DeltaN139INN mutations on a WT Env background do not affect the ability of Env-pseudotyped luciferase reporter viruses to mediate a single cycle of infection in U87.CD4.CCR5 cells. 2013 PLoS pathogens Figure HIV T138N 3 8 Env;Env 44;88 47;91 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. G, Long-term PBMC culture of HIV-1AD8-WT and HIV-1AD8-K601D. 2013 PLoS pathogens Figure HIV K601D 54 59 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. K601D.1 and K601D.2 are 2 independent clones of pAD8-K601D; NL4.3: virus derived from the pNL4.3 clone. 2013 PLoS pathogens Figure HIV K601D;K601D;K601D 12;53;0 17;58;5 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Location and phenotype of K601D. 2013 PLoS pathogens Figure HIV K601D 26 31 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Lysates of metabolically labelled WT, K601D or empty vector (mock) transfected 293T cells (c) and corresponding culture supernatants (s) were immunoprecipitated with IgG14 and protein G Sepharose. 2013 PLoS pathogens Figure HIV K601D 38 43 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Sensitivity of T138N and DeltaN139INN mutant pseudovirions to NAbs. 2013 PLoS pathogens Figure HIV T138N 15 20 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. WT, T138N/L494I/K601N and DeltaN139INN/K601N viruses were incubated with sCD4-IgG2 for 4 h at 37 C and then added to TZM-bl cells. 2013 PLoS pathogens Figure HIV K601N;L494I;T138N;K601N 16;10;4;39 21;15;9;44 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. WT: blue square; T138N/L494I/K601N: red triangle; DeltaN139INN/K601N: green "X". 2013 PLoS pathogens Figure HIV K601N;L494I;T138N;K601N 29;23;17;63 34;28;22;68 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. WT: blue squares, T138N: red triangles, DeltaN139INN: green "X"s. 2013 PLoS pathogens Figure HIV T138N 18 23 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. (A) 293T, HeLa, NP2 and GHOST cells were transfected with four different plasmids (WT, DeltaVpu, L30E and L30E-DeltaVpu). 2013 PloS one Figure HIV L30E;L30E 97;106 101;110 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. (A) PBMC obtained from two healthy seronegative donors were infected with equal focus-forming units (FFU) of WT and mutant (DeltaVpu, L30E, L30E-DeltaVpu) viruses pseudotyped with VSV-G. 2013 PloS one Figure HIV L30E;L30E 134;140 138;144 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. (D) Infectivity of primary viruses carrying Gag L30E mutation in presence and absence of Vpu. 2013 PloS one Figure HIV L30E 48 52 Vpu;Gag 89;44 92;47 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. (E) Western blot analysis of L30E and L30E-DeltaVpu (double mutant) primary viruses. 2013 PloS one Figure HIV L30E;L30E 29;38 33;42 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. (F) Densitometry analysis of L30E and L30E-DeltaVpu viral proteins, p24 and gp41. 2013 PloS one Figure HIV L30E;L30E 29;38 33;42 gp41;p24 76;68 80;71 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Diagram represent clones possessing Gag MA mutation (L30E), Vpu start codon mutation and HIV-1 pNL-AD8 Envelope deficient backbones possessing Gag MA (L30E) and Vpu start codon mutations. 2013 PloS one Figure HIV L30E;L30E 53;151 57;155 Env;Vpu;Vpu;Gag;Gag;Matrix;Matrix 103;60;161;36;143;40;147 111;63;164;39;146;42;149 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Effect of Vpu start codon mutation and Gag L30E mutation on infectivity and Env incorporation of primary viruses of diverse origin. 2013 PloS one Figure HIV L30E 43 47 Vpu;Env;Gag 10;76;39 13;79;42 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. HeLa cells were transfected with WT and mutant plasmids (L30E, DeltaVpu, L30E-DeltaVpu). 2013 PloS one Figure HIV L30E;L30E 57;73 61;77 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Significance in the increased infectivity of double mutant viruses (L30E-DeltaVpu) was determined with respect to L30E and DeltaVpu viruses using Student's t-test: * means p<0.05 and ** means P<0.005. 2013 PloS one Figure HIV L30E;L30E 68;114 72;118 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Significance level of improved infectivity of double mutant viruses (L30E-DeltaVpu) was determined with respect to viruses possessing Gag mutation (L30E) using Student's t-test: * means p<0.05 and ** means P<0.005. 2013 PloS one Figure HIV L30E;L30E 69;148 73;152 Gag 134 137 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Virus propagation of Vpu and Gag L30E mutants in monocyte-derived macrophages. 2013 PloS one Figure HIV L30E 33 37 Vpu;Gag 21;29 24;32 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Virus propagation of Vpu and Gag L30E mutants in PBMC. 2013 PloS one Figure HIV L30E 33 37 Vpu;Gag 21;29 24;32 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Viruses were produced by co-transfection of 293T cells with combinations of Env deficient backbone plasmids containing Gag (L30E) or Vpu mutation and Env plasmids of patient origin. 2013 PloS one Figure HIV L30E 124 128 Vpu;Env;Env;Gag 133;76;150;119 136;79;153;122 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Vpu start codon mutation rescued infectivity of defective Gag MA mutant (L30E) viruses by modulating Env incorporation on released virions. 2013 PloS one Figure HIV L30E 73 77 Vpu;Env;Gag;Matrix 0;101;58;62 3;104;61;64 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. (A) Wild type and W596L/K601D-mutated HIV-1AD8 virus stocks produced by transfected 293T cells were normalized according to RT activity and used to infect U87.CD4.CCR5 cells. 2013 Retrovirology Figure HIV K601D;W596L 24;18 29;23 RT 124 126 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. (B) Infection of U87.CD4.CCR5 cells was initiated with VSV G-pseudotyped WT and W596L/K601D mutant viruses. 2013 Retrovirology Figure HIV K601D;W596L 86;80 91;85 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Effects of D674E and D674N mutations on viral spread initiated by cell-free (D) and cell-associated (E) virus in 10-day U87.CD4.CCR5 cultures. 2013 Retrovirology Figure HIV D674E;D674N 11;21 16;26 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Long-term culture of W596L/K601D virus. 2013 Retrovirology Figure HIV K601D;W596L 27;21 32;26 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Lysates of metabolically labeled WT, K601D, WL/KD, W596L or empty vector (No Env) transfected 293T cells (c) and corresponding culture supernatants (s) were immunoprecipitated with pooled IgG from HIV-1-infected persons and protein G-Sepharose. 2013 Retrovirology Figure HIV K601D;W596L 37;51 42;56 Env 77 80 HIV infections 197 211 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. Amino acid sequences of the consensus HIV-1 clade A integrase (IN_a), its inactive variant containing mutation in the active site D64V (IN_in), and inactive variant with mutations conferring resistance to elvitegravir H51Y, E92Q, S147G, E157Q, K160Q (IN_in_e3), all with Met-Gly dipeptide on the N-terminus (A); Schematic representation of the structure of the synthetic genes. 2013 PloS one Figure HIV D64V;E157Q;E92Q;H51Y;K160Q;S147G 130;237;224;218;244;230 134;242;228;222;249;235 IN 52 61 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. End-point titers of the integrase-specific IgG antibodies in the sera of BALB/c mice immunized with the genes encoding consensus HIV-1 FSU-A integrase (IN_a), consensus IN inactivated by D64V mutation (IN_in), and inactivated consensus integrase carrying mutations conferring resistance to elvitegravir (IN_in_e3). 2013 PloS one Figure HIV D64V 187 191 IN;IN;IN;IN 24;141;236;169 33;150;245;171 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. (A) Sensitivities of mutant viruses SS, SN, and NS to neutralization by MAbs Fab-B404 (anti-V3/V4), Fab-K8 (anti-CD4i), and M318T (anti-V2) are shown. 2013 Frontiers in microbiology Figure HIV M318T 124 129 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Arrows indicate major substitutions as follows: Q733stop, W782stop, V17L, and E176K. 2013 Frontiers in microbiology Figure HIV E176K;Q733X;V17L;W782X 78;48;68;58 83;56;72;66 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Point mutants F277V and N295S were constructed by inserting the substitutions F277V and N295S into SIVmac316, respectively. 2013 Frontiers in microbiology Figure HIV F277V;F277V;N295S;N295S 14;78;24;88 19;83;29;93 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Viral proteins gp120 (A), gp41 (B), and p27 (C) were detected using MAbs M318T (anti-gp120 V2), B408 (anti-gp41 cluster I), and B450 (anti-p27), respectively. 2013 Frontiers in microbiology Figure HIV M318T 73 78 gp120;gp120;gp41;gp41 15;85;26;107 20;90;30;111 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. Viruses were examined for their sensitivities to neutralization by MAbs Fab-B404, Fab-K8, and M318T in TZM-bl cells. 2013 Frontiers in microbiology Figure HIV M318T 94 99 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. HIV-1 Env pseudoviruses bearing the parental clone or Env-selected mutations V2 (V169M), V3 (L317W) and V4 (I408T) in single, double and triple combinations served to infect U87-CD4-CCR5 cells in the presence of increasing MVC and VCV concentrations. 2013 AIDS research and therapy Figure HIV I408T;L317W;V169M 108;93;81 113;98;86 Env;Env 6;54 9;57 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. U87-CD4-CCR5 cells were infected with HIV-1 Env pseudoviruses bearing parental clone (wild type) or Env single mutants V169M, L317W, I408T, double mutants V169M/L317W, V169M/I408T, L317W/I408T and the triple mutant V169M/L317W/I408T. 2013 AIDS research and therapy Figure HIV I408T;L317W;V169M;I408T;I408T;I408T;L317W;L317W;L317W;V169M;V169M;V169M 227;221;215;133;174;187;126;161;181;119;155;168 232;226;220;138;179;192;131;166;186;124;160;173 Env;Env 44;100 47;103 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Using genomic DNA from 293T cells infected with HIV-Luc harboring WT-IN, IID-IN, or catalytic mutant D116A, early RT products were quantified by qRT-PCR at indicated times post-infection. 2013 Retrovirology Figure HIV D116A 101 106 IN;IN;RT 69;77;114 71;79;116 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. ATP- and PPi-dependent rescue of EFdA-MP terminated primers by WT and K65R RTs. 2013 Retrovirology Figure HIV K65R 70 74 RT 75 78 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. dATP (yellow sticks, A and C) and EFdA-TP (cyan sticks, B and D) are shown at the active sites of WT HIV RT, (A and B) or K65R HIV RT (C and D). 2013 Retrovirology Figure HIV K65R 122 126 RT;RT 105;131 107;133 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Effect of K65R mutation on the translocation state of RT bound to T/PEFdA-MP. 2013 Retrovirology Figure HIV K65R 10 14 RT 54 56 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Inhibition of WT and K65R RT-catalyzed DNA synthesis by EFdA-TP. 2013 Retrovirology Figure HIV K65R 21 25 RT 26 28 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Molecular models of dATP and EFdA-TP in the active sites of WT and K65R HIV RT. 2013 Retrovirology Figure HIV K65R 67 71 RT 76 78 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Purified Td31/Pd18-P0-EFdA-MP was incubated with WT or K65R RT in the presence of 10 mM MgCl2, 3.5 mM ATP, 100 muM dATP, 0.5 muM dTTP, and 10 muM ddGTP at 37 C. 2013 Retrovirology Figure HIV K65R 55 59 RT 60 62 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Purified Td31/Pd18-P0-EFdA-MP was incubated with WT or K65R RT in the presence of 6 mM MgCl2, 150 muM PPi, 100 muM dATP, 0.5 muM dTTP, and 10 muM ddGTP at 37 C. 2013 Retrovirology Figure HIV K65R 55 59 RT 60 62 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Td31/Pd18-P0 was incubated with WT or K65R HIV-1 RT for 50 minutes in the presence of 1 muM dNTPs, MgCl2 and increasing concentrations of EFdA-TP (0-1,500 nM). 2013 Retrovirology Figure HIV K65R 38 42 RT 49 51 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Td43/Pd30-EFdA-MP (100 nM) with 5'-Cy3-label on the DNA template was incubated with WT or K65R HIV-1 RT (600 nM) and various concentrations of the next incoming nucleotide (dTTP). 2013 Retrovirology Figure HIV K65R 90 94 RT 101 103 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. (A) Equal amounts of p24 of EU-labeled WT HIV-1 and E45A HIV-1 were treated with cell extraction buffer for 15 minutes, fixed onto slides, and then stained for EU (green) and NC (red). 2013 Retrovirology Figure HIV E45A 52 56 p24;NC 21;175 24;177 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. (B) RNA staining of WT HIV-1 and E45A HIV-1 was counted alone and when co-localized with NC. 2013 Retrovirology Figure HIV E45A 33 37 NC 89 91 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. (C) Equal amounts of p24 of EU-labeled WT HIV-1 and E45A HIV-1 also containing MS2-GFP (green) were treated with cell extraction buffer for 15 minutes, fixed, and stained for EU (red). 2013 Retrovirology Figure HIV E45A 52 56 p24 21 24 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. (C) TZM-bl cells were infected with WT HIV-1 or the D443N RT mutant and stained for EU at multiple time points. 2013 Retrovirology Figure HIV D443N 52 57 RT 58 60 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. E45A HIV-1 cores allow vRNA and NC staining more readily than WT HIV-1 cores. 2013 Retrovirology Figure HIV E45A 0 4 NC 32 34 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Early viral reverse transcripts (RU5) were measured by qPCR from TZM-bl cells infected with equal p24 levels of WT, E45A, K203A, and 5Mut HIV-1. 2013 Retrovirology Figure HIV E45A;K203A 116;122 120;127 p24 98 101 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Initiation of reverse transcription was more rapid in E45A HIV-1 compared to WT, K203A, and 5Mut HIV-1. 2013 Retrovirology Figure HIV E45A;K203A 54;81 58;86 RT 14 35 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. TZM-bl cells were infected with (A) EU-labeled WT, E45A, K203A, 5Mut, and E45A/R132T HIV-1; or (B) EU-labeled WT and 5Mut HIV-1 in the presence and absence of 10 muM PF74. 2013 Retrovirology Figure HIV E45A;E45A;K203A;R132T 51;74;57;79 55;78;62;84 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. (A) Five amino acid substitutions in the V3 loop of HIV-1V3-M5 (I304V/F312W/T314A/E317D/I318V). 2013 PloS one Figure HIV E317D;F312W;I304V;I318V;T314A 82;70;64;88;76 87;75;69;93;81 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. The effect of 1 microM of maraviroc on p24 Gag production in HIV-1JR-FLan, HIV-1T199K, HIV-1V3-M5, HIV-1V3-M5/T199K, HIV-1234, and HIV-1234/T199K. 2013 PloS one Figure HIV T199K;T199K 110;140 115;145 p24;Gag 39;43 42;46 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. The effect of 1 microM of maraviroc on p24 Gag production in recombinant viruses containing four amino acid substitutions plus T199K. 2013 PloS one Figure HIV T199K 127 132 p24;Gag 39;43 42;46 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. Point mutations numbered 1-4 are as follows: 1 for K103N, 2 for V106M, 3 for Y188C/L, 4 for G190A. 2013 Retrovirology Figure HIV G190A;K103N;V106M;Y188C;Y188L 92;51;64;77;77 97;56;69;84;84 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. The arrow indicates the location of the K103N mutation in the RT gene in consensus and all SGA sequences (AAA to AAC mutation). 2013 Retrovirology Figure HIV K103N 40 45 RT 62 64 23941304 Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis. The arrow represents the location of the K103N mutation. 2013 Retrovirology Figure HIV K103N 41 46 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. *Major NFV-resistance mutation L90M was found in the protease in the case of KF307. 2013 PloS one Figure HIV L90M 31 35 PR 53 61 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. (B) Actual BN-PAGE Western blots showing mAb binding to parent, D368R and R469S SOS-VLPs. 2013 PloS one Figure HIV D368R;R469S 64;74 69;79 23991039 A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. (C) Titration of the 1F7 mAb against parent and D368R SOS-VLPs. 2013 PloS one Figure HIV D368R 48 53 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. At each step the frequencies for V82A, I54V, V71A, M46I, L90M and I84V were recorded. 2013 PloS one Figure HIV I54V;I84V;L90M;M46I;V71A;V82A 39;66;57;51;45;33 43;70;61;55;49;37 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Box-and-whiskers plots of odds ratios observed between observed and expected frequencies of L90M produced by the linear models for various PI related mutations. 2013 PloS one Figure HIV L90M 92 96 PI 139 141 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Construction of the L90M frequency linear model. 2013 PloS one Figure HIV L90M 20 24 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. First, the sequence set is split into two groups; one devoid of the mutation of interest, in this case PR M46I, and the other that contains the mutation. 2013 PloS one Figure HIV M46I 106 110 PR 103 105 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. From this data, a linear model specific to a particular mutation, M46I in this case was constructed. 2013 PloS one Figure HIV M46I 66 70 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The annotation of the x-axis tick marks represent the model used for calculation of the expected L90M frequency. 2013 PloS one Figure HIV L90M 97 101 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The figure demonstrates the procedure to construct the data sets used to predict the expected frequency of L90M considering the frequency of co-occurring mutations. 2013 PloS one Figure HIV L90M 107 111 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The patient ID in the mutation negative-set are increasingly replaced with patient sequence sets from the M46I group. 2013 PloS one Figure HIV M46I 106 110 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. (A) Purified WT or T174I-IN mutant HIV-1 produced in the presence of DMSO or GS-B was briefly treated with cross-linking agent BS3 and the IN monomeric and dimeric forms assessed by anti-IN Western blot analysis. 2013 PloS one Figure HIV T174I 19 24 IN;IN;IN 25;139;187 27;141;189 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. (C) Quantitative PCR assessment of early RT and late RT product formation in MT-2 cells infected with T174I virus produced and infected in the presence of GS-B (1 microM) or EFV (1 microM). 2013 PloS one Figure HIV T174I 102 107 RT;RT 41;53 43;55 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. EC50 values for ATV, RAL, GS-A, and GS-B for WT and T174I-IN mutant virus measured under the three compound exposure conditions are tabulated. 2013 PloS one Figure HIV T174I 52 57 IN 58 60 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Frequencies of the different core phenotypes are shown for WT (B) and T174I mutant (C) HIV-1 produced in the presence of DMSO (gray bars) or 1 microM GS-B (black bars). 2013 PloS one Figure HIV T174I 70 75 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Wild-type and T174I mutant HIV-1 was produced in the presence of DMSO or GS-B (1 microM) and fractionated over a detergent-layered sucrose gradient. 2013 PloS one Figure HIV T174I 14 19 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. (A) The Q148H/G140S mutations are predicted to disrupt the structure of the flexible active-site loop, displacing the 310 helix away from the DDE motif and weakening the H-bond interaction between the backbone CO of Q148H and the backbone NH of E152. 2013 PloS one Figure HIV G140S;Q148H;Q148H 14;8;216 19;13;221 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. (B) The N155H mutation is predicted to disrupt the structure of the alpha4 helix, widen the base of the catalytic pocket, alter the placement of at least the Mg2+ ion coordinated to residues D64 and E152 and alter the conformation of the terminal 3' adenosine forming part of the pocket. 2013 PloS one Figure HIV N155H 8 13 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Structural model of Q148R HIV-1 integrase with U5 LTR DNA. 2013 PloS one Figure HIV Q148R 20 25 IN;LTR 32;50 41;53 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Structural models of (A) Q148H/G140S and (B) N155H HIV-1 integrase with U5 LTR DNA and dolutegravir. 2013 PloS one Figure HIV G140S;N155H;Q148H 31;43;23 36;50;30 IN;LTR 57;75 66;78 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The side chain of residue Q148R was modeled interacting with the side chain of E152 and in this conformation the residue may interfere with the binding of elvitegravir. 2013 PloS one Figure HIV Q148R 26 31 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. (A) Percent of CD4+ T cells out of total T cells from bone marrow, lymph node, liver, lung and spleen from unexposed BLT mice (Naive, n = 8) were compared to groups of BLT mice exposed to LAI (n = 7) or LAINefP72A/P75A (n = 4). 2013 Retrovirology Figure HIV P75A 214 218 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. (A) Viral loads of BLT mice were plotted for BLT humanized mice that were exposed to 90,000 TCIU of LAI (n = 7) and LAINefP72A/P75A (n = 4). 2013 Retrovirology Figure HIV P75A 127 131 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. (B) A3.01 cells were infected with LAI and LAINefP72A/P75A at multiplicity of infection of 0.05 and viral production followed for 20 days with ELISA for p24gag. 2013 Retrovirology Figure HIV P75A 54 58 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. (C) LAI, LAINeffs and pLAINefP72A/P75A were titered using HeLa-MAGI indicator cells and p24gag quantitated by ELISA. 2013 Retrovirology Figure HIV P75A 34 38 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. (D) Nefs encoded by LAINefP72A/P75A and LAI were expressed in CEM cells following transduction with retroviral vectors (LXSN). 2013 Retrovirology Figure HIV P75A 31 35 Nef 4 8 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Analysis of CD4+ T cells from tissues from mice exposed to LAI or LAINefP72A/P75A. 2013 Retrovirology Figure HIV P75A 77 81 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. CEM cells expressing LAI Nef and LAI NefP72A/P75A were analyzed by flow cytometry for cell surface CD4 and MHC Class I expression. 2013 Retrovirology Figure HIV P75A 45 49 Nef;Nef 25;37 28;40 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Delayed partial reversion of P72A/P75A.nef sequences were obtained from viral RNA in plasma of four LAINefP72A/P75A infected mice from Figure 7. 2013 Retrovirology Figure HIV P72A;P72A;P75A;P75A 29;106;34;111 33;110;38;115 Nef 39 42 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. LAINefP72A/P75A replicates in A3.01 T cells and is functional for CD4 downregulation. 2013 Retrovirology Figure HIV P75A 11 15 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. pLAI, pLAINeffs and pLAINefP72A/P75A proviral clones were transfected into 293T cells and virus harvested from the media. 2013 Retrovirology Figure HIV P75A 32 36 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. The wild type proline codons that were mutated to alanine are P72A (left panel headed by GCT) and P75A (right panel headed by GCT). 2013 Retrovirology Figure HIV P72A;P75A 62;98 66;102 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. This was the reversion of the P75A mutation back to proline. 2013 Retrovirology Figure HIV P75A 30 34 24172637 In vivo analysis of highly conserved Nef activities in HIV-1 replication and pathogenesis. Viral load analysis and peripheral blood CD4+ T cell depletion in mice infected with LAINefP72A/P75A. 2013 Retrovirology Figure HIV P75A 96 100 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. Env D470N and E84K determine efficiency of CCR5 and GPR15 use. 2013 Retrovirology Figure HIV D470N;E84K 4;14 9;18 Env 0 3 24219995 Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. Mutations that emerged in vivo which conferred CD4 independence (D470N and E84K) were introduced into CD4-dependent Envs, and mutations that abrogate CD4 independence (N470D and K84E) were introduced into CD4-independent Envs. 2013 Retrovirology Figure HIV D470N;E84K;K84E;N470D 65;75;178;168 71;79;182;174 Env;Env 116;221 120;225 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. 293T cells were cotransfected with an Env-defective pNL4-3 derivative (pNL4-3/KFS) and vectors expressing WT or V120Q/A327P Env, or VSV-G expression vector. 2013 Retrovirology Figure HIV A327P;V120Q 118;112 123;117 Env;Env 38;124 41;127 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. 293T cells were transfected with WT and V120Q/A327P molecular clones, six hours posttransfection cells were treated with indicated concentrations of NYAD-36, -66, and -67 and virions were collected after 2 days as in Figure 7. 2013 Retrovirology Figure HIV A327P;V120Q 46;40 51;45 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Env mutant V120Q/A327P replicates in the presence of stapled peptides. 2013 Retrovirology Figure HIV A327P;V120Q 17;11 22;16 Env 0 3 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Jurkat T-cell line (a) and PBMCs (b-d) were infected with RT-normalized WT- and V120Q/A327P mutant viruses and cultured in the presence of 30 uM stapled peptides and replication was monitored as described in the Figure 8 legend. 2013 Retrovirology Figure HIV A327P;V120Q 86;80 91;85 RT 58 60 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Overlay of 2D 1H-15N HSQC spectra obtained for the HIV-1 capsid monomer (P24-W184A/M185A) protein upon titration with NYAD-36. 2013 Retrovirology Figure HIV M185A;W184A 83;77 88;82 Capsid;p24 57;73 63;76 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Replication of WT and V120Q/A327P Env mutant was carried in the presence of 37.5 muM stapled peptides as described in the Figure 8 legend. 2013 Retrovirology Figure HIV A327P;V120Q 28;22 33;27 Env 34 37 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Stapled peptides were added to TZM-bl cells at indicated concentrations during the 2 h infection for WT and Env mutant (V120Q/A327P) viruses. 2013 Retrovirology Figure HIV A327P;V120Q 126;120 131;125 Env 108 111 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. The Env mutant V120Q/A327P is replication defective in PBMC. 2013 Retrovirology Figure HIV A327P;V120Q 21;15 26;20 Env 4 7 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. V120Q/A327P mutant virions produced in the presence of stapled peptides were defective in single-cycle infectivity assay. 2013 Retrovirology Figure HIV A327P;V120Q 6;0 11;5 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Alix paired with Y36S serves as the negative control. 2013 Retrovirology Figure HIV Y36S 17 21 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Beta-galactosidase units were normalized to P7L paired with Alix. 2013 Retrovirology Figure HIV P7L 44 47 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. CA[P99A]-p6[P7L-S40F] Panel A, P7L; panel B, CA [EE75,76AA]-p6[P7L]; panel C, CA[P99A]-p6[P7L]; panel D, P7L-S40F; panel E, CA[EE75,76AA]-p6[P7L-S40F]; and panel F, CA[P99A]-p6[P7L-S40F]. 2013 Retrovirology Figure HIV P7L;P7L;P99A;P99A;P99A;S40F;S40F;S40F;S40F;P7L;P7L;P7L 31;105;3;81;168;16;109;145;181;12;141;177 34;108;7;85;172;20;113;149;185;15;144;180 Gag;Gag;Gag;Gag;Gag;Capsid;Capsid;Capsid;Capsid;Capsid 9;60;87;138;174;0;45;78;124;165 11;62;89;140;176;2;47;80;126;167 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. COS-1 cells were transfected with plasmids expressing HA-tagged -P7L (panels A and D), P7L-S40F (panels B and E), or P7L-Y36S-S40F (panels C and F). 2013 Retrovirology Figure HIV P7L;P7L;P7L;S40F;S40F;Y36S 65;87;117;91;126;121 68;90;120;95;130;125 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. COS-1 cells were transfected with plasmids expressing HA-tagged HIV-1 Gag-P7L (panels A1 and A2) or P7L-S40F (panels B1 and B2) and prepared for examination by electron microscopy as described in Methods. 2013 Retrovirology Figure HIV P7L;P7L;S40F 74;100;104 77;103;108 Gag 70 73 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. COS-1 cells were transfected with plasmids expressing HA-tagged HIV-1 Gag-WT (panels A and B) or Gag-S40F (panels C and D). 2013 Retrovirology Figure HIV S40F 101 105 Gag;Gag 70;97 73;100 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Disrupting Alix interaction with S40F restores spherical particle formation. 2013 Retrovirology Figure HIV S40F 33 37 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Disrupting L domain-1 increases the effect of the S40F mutation on budding. 2013 Retrovirology Figure HIV S40F 50 54 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Panel B, Electron microscopy of particles associated with cells transfected with pNL4-3DeltaEnv-WT (panel B1), or S40F (panel B2). 2013 Retrovirology Figure HIV S40F 114 118 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Panel B, Quantitative analysis of VLP release efficiency [VLP/(VLP + Gag from cell lysate)] were determined as described in Methods (n = 7; 3 independent constructs of P7L-S40F-Gag). 2013 Retrovirology Figure HIV P7L;S40F 168;172 171;176 Gag;Gag 69;177 72;180 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Panel C, The beta-galactosidase signal is undetectable when the S40 mutants are paired with Alix F676D. 2013 Retrovirology Figure HIV F676D 97 102 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Panels A1-A3, Western blot analysis of pNL4-3DeltaEnv WT, S40A and S40F constructs which encode active protease. 2013 Retrovirology Figure HIV S40A;S40F 58;67 62;71 PR 103 111 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The budding defect resulting from S40F mutation becomes more apparent when PR is inactive. 2013 Retrovirology Figure HIV S40F 34 38 PR 75 77 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40A and S40F results represent five independent clones tested in 5 independent assays. 2013 Retrovirology Figure HIV S40A;S40F 4;13 8;17 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40F mutation increases the disruption of virus release due to nonfunctional L domains-1 and -2. 2013 Retrovirology Figure HIV S40F 4 8 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40F mutation partially rescues the block to VLP release efficiency imposed by mutations in the CA NTD. 2013 Retrovirology Figure HIV S40F 4 8 Capsid 100 102 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. The S40F mutation suppresses the block to budding imposed by CA[EE75,76AA] and CA[P99A]. 2013 Retrovirology Figure HIV P99A;S40F 82;4 86;8 Capsid;Capsid 61;79 63;81 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Tsg101 plus P7L and Alix plus P7L-Y36S are negative controls. 2013 Retrovirology Figure HIV P7L;P7L;Y36S 12;30;34 15;33;38 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. VLPs and cell lysates from COS-1 cells transfected with pNL4-3DeltaEnv-WT (lane 1), pNL4-3DeltaEnv-S40A (lane 2) or pNL4-3DeltaEnv-S40F (lane 3) were analyzed by Western blotting. 2013 Retrovirology Figure HIV S40A;S40F 99;131 103;135 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. VLPs and cell lysates from the COS-1 cells transfected with HA-tagged HIV-1 Gag-P7L (lane 1), P7L-S40F (lane 2) were analyzed by Western blotting and gag related proteins identified by monoclonal HA antibody. 2013 Retrovirology Figure HIV P7L;P7L;S40F 80;94;98 83;97;102 Gag;Gag 76;150 79;153 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. WT Gag, P7L-S40A and P7L-S40F were each paired with wild type Alix or its F676D mutant which does not bind to Gag. 2013 Retrovirology Figure HIV F676D;P7L;P7L;S40A;S40F 74;8;21;12;25 79;11;24;16;29 Gag;Gag 3;110 6;113 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Five amino acid changes were identified to be associated with HLA-B*57/58:01 disease progression: S126N, L215T, H219Q, M228I and N252H. 2013 PloS one Figure HIV H219Q;L215T;M228I;N252H;S126N 112;105;119;129;98 117;110;124;134;103 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Replication kinetics (days 2-17) of constructed NL4-3.Ba-L viral variants containing mutations associated with HLA-B*57/58:01 (I147L, V159I, S173T, T242N, G248A and T280V; red), in combination with mutation S126N (orange), L215T (yellow), H219Q (purple), M228I (green), L215T and H219Q (grey), or a combination of all 5 compensatory mutations (S126N, L215T, H219Q, M228I and N252H; blue). 2013 PloS one Figure HIV G248A;H219Q;H219Q;H219Q;I147L;L215T;L215T;L215T;M228I;M228I;N252H;S126N;S126N;S173T;T242N;T280V;V159I 155;239;280;358;127;223;270;351;255;365;375;207;344;141;148;165;134 160;244;285;363;132;228;275;356;260;370;380;212;349;146;153;170;139 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Replication kinetics of NL4-3.Ba-L and constructed NL4-3.Ba-L viral variants containing mutations associated with HLA-B*57/58:01 (I147L, V159I, S173T, T242N, G248A and T280V) in the absence or presence of compensatory mutations described by Brockman et al. 2013 PloS one Figure HIV G248A;I147L;S173T;T242N;T280V;V159I 158;130;144;151;168;137 163;135;149;156;173;142 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Replication kinetics of NL4-3.Ba-L and constructed NL4-3.Ba-L viral variants containing mutations associated with HLA-B*57/58:01 (I147L, V159I, S173T, T242N, G248A and T280V) in the absence or presence of compensatory mutations. 2013 PloS one Figure HIV G248A;I147L;S173T;T242N;T280V;V159I 158;130;144;151;168;137 163;135;149;156;173;142 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Six amino acid changes were identified to be specifically associated with the presence of HLA-B*57/58:01: I147L, V159I, S173T, T242N, G248A and T280V. 2013 PloS one Figure HIV G248A;I147L;S173T;T242N;T280V;V159I 134;106;120;127;144;113 139;111;125;132;149;118 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Assay reactivity with wild-type and M46I/L mutation clinical samples. 2013 PloS one Figure HIV M46I;M46L 36;36 42;42 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Cloned M46I (A.) and M46L (B.) mutant virus template was diluted 10-fold, from 100% to 0.0001%, in backgrounds of wild-type sequence to determine assay detection limits. 2013 PloS one Figure HIV M46I;M46L 7;21 11;25 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Open circles (black color) are virus with M46I detected by bulk sequencing. 2013 PloS one Figure HIV M46I 42 46 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. PC; Positive clones with M46I/L, NC; Negative clone with no M46I/L(wild type). 2013 PloS one Figure HIV M46I;M46I;M46L;M46L 25;60;25;60 31;66;31;66 NC 33 35 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Phylogenetic tree of samples with or without minority variants of M46I/L or L90M drug resistance. 2013 PloS one Figure HIV L90M;M46I;M46L 76;66;66 80;72;72 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Solid squares (red color) indicate sequences of M46I-specific amplicons and solid triangle (red color) indicate sequences of M46L amplicons; open circles (red color) indicate bulk sequences for persons with minority M46I/L mutations; X and Y are pairs of closely related transmitted M46I sequences. 2013 PloS one Figure HIV M46I;M46I;M46I;M46L;M46L 48;216;283;216;125 52;222;287;222;129 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Solid squares indicate L90M-specific amplicon sequences; open squares indicate bulk sequences for persons with minority L90M mutations. 2013 PloS one Figure HIV L90M;L90M 23;120 27;124 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. A) While Vif wild-type and H28A mutant pull down Cul5 efficiently, H27A, M29A and Y30A mutants are unable to bind Cul5 efficiently. 2014 Retrovirology Figure HIV H27A;H28A;M29A;Y30A 67;27;73;82 71;31;77;86 Vif 9 12 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Imaging demonstrates that the Vif double mutant V25/H27A and single mutant H108A localize to the cytoplasm of the cell similar to wild-type. 2014 Retrovirology Figure HIV H27A;H108A 52;75 56;80 Vif 30 33 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Select Vif N-terminal mutants (V25A, H27A, M29A, and Y30A) that do not efficiently degrade A3G and A3F have a reduced ability to co-precipitate Cul5; however, CBF-beta and Elo B/C can still bind Vif. 2014 Retrovirology Figure HIV H27A;M29A;V25A;Y30A 37;43;31;53 41;47;35;57 Vif;Vif 7;195 10;198 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Addition of M50I to R263K does not increase integrase strand-transfer activity. 2014 Retrovirology Figure HIV M50I;R263K 12;20 16;25 IN 44 53 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Effects of the M50I and R263K mutations on HIV infectivity in TZM-bl cells (A) and replication capacity in PM1 cells (B). 2014 Retrovirology Figure HIV M50I;R263K 15;24 19;29 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. M50I does not compensate for the reduction in HIV replication associated with R263K. 2014 Retrovirology Figure HIV R263K;M50I 78;0 83;4 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Occurrence of the M50I polymorphism in treatment-naive individuals living with HIV-1 subtype B. 2014 Retrovirology Figure HIV M50I 18 22 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Sequence analysis of subtype B integrase of 2,253 clinical isolates from treatment-naive patients from the Stanford HIV Drug Resistance Database for the following polymorphisms: M50M, M50I, M50T, M50L and M50R. 2014 Retrovirology Figure HIV M50I;M50L;M50M;M50R;M50T 184;196;178;205;190 188;200;182;209;194 IN 31 40 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. The effect of M50I with R263K on enzyme activity. 2014 Retrovirology Figure HIV M50I;R263K 14;24 18;29 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. (C) Cells were challenged with viruses bearing the indicated capsid mutations (P90A, G89V, P90A/A92E, G89V/A92E). 2014 Retrovirology Figure HIV A92E;A92E;G89V;G89V;P90A;P90A 96;107;85;102;79;91 100;111;89;106;83;95 Capsid 61 67 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. 32 HeLa cell clones were treated with 5 muM CsA or DMSO as control and challenged with an HIV-1-GFP reporter vector bearing the A92E CA mutation. 2014 Retrovirology Figure HIV A92E 128 132 Capsid 133 135 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. A panel of 27 cell lines and human CD4+ T cells were treated with 5 muM CsA or DMSO as control and challenged with an HIV-1-GFP reporter vector bearing the A92E CA mutation. 2014 Retrovirology Figure HIV A92E 156 160 Capsid 161 163 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. HeLa clone 3D (A) and MT4 cells (B), stably expressing the WT or mutated (H436Q) hT5Cyp restriction factor, were treated with CsA or DMSO as control, and challenged with HIV-1-GFP reporter viruses bearing WT, G89V or A92E mutant capsid. 2014 Retrovirology Figure HIV A92E;G89V;H436Q 217;209;74 221;213;79 Capsid 229 235 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The cells were (A) depleted of endogenous CypA or (B) pre-treated with 5 muM CsA or DMSO and challenged with WT or A92E CA mutant virus. 2014 Retrovirology Figure HIV A92E 115 119 Capsid 120 122 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The CypA-CA interaction hyper-stabilizes HIV-1 CA cores in a target cell-specific fashion.env-minus HIV-1, pseudotyped with VSV G, and bearing either WT or A92E mutant CA, was incubated with HeLa clone 3D (A) or MT4 cells (B) stably expressing hT5Cyp or hT5Cyp-H436Q, as indicated. 2014 Retrovirology Figure HIV A92E;H436Q 156;261 160;266 Env;Capsid;Capsid;Capsid 90;9;47;168 93;11;49;170 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The ratio of A92E mutant virus infectivity in CsA vs DMSO treated cells is shown. 2014 Retrovirology Figure HIV A92E 13 17 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Variable effect of CsA on transduction of different cell lines by HIV-1 bearing the A92E CA mutant. 2014 Retrovirology Figure HIV A92E 84 88 Capsid 89 91 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Variable effect of CsA on transduction of different HeLa cell clones by HIV-1 bearing the A92E CA mutation. 2014 Retrovirology Figure HIV A92E 90 94 Capsid 95 97 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. B) At 72 hours, the transfected cells were challenged with WT or N74D CA HIV-1luc and analysed 48 hours after for luciferase activities. 2014 PLoS pathogens Figure HIV N74D 65 69 Capsid 70 72 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. B) MEFs treated with siRNAs (solid black bars: control siRNA; hatched gray bars: TNPO3 siRNA) were challenged with WT or N74D HIV-1 reporter virus. 2014 PLoS pathogens Figure HIV N74D 121 125 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. E) Indicated cell lines were challenged with an HIV-1luc N74D capsid mutant virus. 2014 PLoS pathogens Figure HIV N74D 57 61 Capsid 62 68 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. E) Parental and restriction factor-expressing CrFK cells (OMTC, OMThNC, OMTmNC) were challenged with WT HIV-1luc, N74D HIV-1luc,, FIVluc, and NB-MLVluc. 2014 PLoS pathogens Figure HIV N74D 114 118 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Experiments are representative of N = 3 for wild type capsid HIV-1, N = 2 for G89V capsid HIV-1, and N = 2 for SIVmac. 2014 PLoS pathogens Figure HIV G89V 78 82 Capsid;Capsid 54;83 60;89 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. F) Control (black bars) and stable Nup358 knockdown cells (hatched bars) were challenged with HIV-1luc (WT or N74D), FIVluc, and MLVluc. 2014 PLoS pathogens Figure HIV N74D 110 114 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. F) Wild type reporter virus HIV-1luc and capsid mutant N74D HIV-1luc were used to infect Nup358F/F, Nup358F/F+Cre and Nup358-/-[GFP1-1340] cells. 2014 PLoS pathogens Figure HIV N74D 56 60 Capsid 42 48 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. G) HIV-1luc D64N was used to infect the indicated cell lines and 2-LTR circles were measured in triplicate 22 hours post-infection. 2014 PLoS pathogens Figure HIV D64N 12 16 LTR 67 70 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. G) Results of 2-LTR circle measurements (n = 5 experiments) in stable Nup358-/-[GFP1-1340] knockout cells, presented as a percentage of the values obtained in parental Nup358F/F cells are shown for an integration competent (WT) and an integration mutant (IN D64N) HIV-1luc. 2014 PLoS pathogens Figure HIV D64N 258 262 LTR;IN 16;255 19;257 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. G89V vector gave the same result as G89A vector (data not shown). 2014 PLoS pathogens Figure HIV G89A;G89V 36;0 40;4 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Statistical analysis was performed using two tailed T-test, p-values were 0.038 and 0.02 for WT and D64N samples respectively. 2014 PLoS pathogens Figure HIV D64N 100 104 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. The experiment shown is representative of N = 3 for wild type capsid and N = 2 for N74D capsid. 2014 PLoS pathogens Figure HIV N74D 83 87 Capsid;Capsid 62;88 68;94 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Wild-type (WT), resistant and D29V mutant proteases coupled to darunavir (top) and tipranavir (bottom). 2014 BMC bioinformatics Figure HIV D29V 30 34 PR 42 51 24629078 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. Wild-type and D29V mutant protease structures. 2014 BMC bioinformatics Figure HIV D29V 14 18 PR 26 34 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. (A) Fo - Fc omit map contoured at 2.0sigma showing one molecule of DRV (yellow sticks) in the crystal structure of the monomer of PRP51-D25N/DRV. 2014 ACS chemical biology Figure HIV D25N 136 140 PR 130 132 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. (A) Superposition of the overall structures of PRP51-D25N (pink) and PR20/p2-NCopen (PDB ID 3UHL, blue). 2014 ACS chemical biology Figure HIV D25N 53 57 PR;PR 47;69 49;71 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. (A) Superposition of the overall structures of PRP51-D25N (pink) and PRP51-D25N/DRV (green). 2014 ACS chemical biology Figure HIV D25N 75 79 PR;PR 47;69 49;71 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. (B) A different position and conformation was seen for the two molecules of DRV (red sticks and pink sticks) bound symmetrically in the PRP51-D25N dimer (green color). 2014 ACS chemical biology Figure HIV D25N 142 146 PR 136 138 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. (B) Interaction between two DRV molecules in the PRP51-D25N dimer (yellow sticks and cyan sticks). 2014 ACS chemical biology Figure HIV D25N 55 59 PR 49 51 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. (B) The flap residues 47-53 and Pro81 of PRP51-D25N and PR20/p2-NCopen are shown below. 2014 ACS chemical biology Figure HIV D25N 47 51 PR;PR 41;56 43;58 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. (C,D) Interactions of DRV with PRP51-D25N (green sticks). 2014 ACS chemical biology Figure HIV D25N 37 41 PR 31 33 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Comparison of dimers of PRP51-D25N and PR20/p2-NCopen (PDB ID 3UF3). 2014 ACS chemical biology Figure HIV D25N 30 34 PR;PR 24;39 26;41 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Comparison of two structures of PRP51-D25N. 2014 ACS chemical biology Figure HIV D25N 38 42 PR 32 34 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. DRV binds to different sites in PR and PRP51-D25N. 2014 ACS chemical biology Figure HIV D25N 45 49 PR;PR 32;39 34;41 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. DRV has distinct hydrogen bond interactions with wild-type PR (PDB ID 2IEN) (A) and PRP51-D25N (B). 2014 ACS chemical biology Figure HIV D25N 90 94 PR;PR 59;84 61;86 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. DRV is represented in gray sticks and yellow sticks in PR and PRP51-D25N, respectively. 2014 ACS chemical biology Figure HIV D25N 68 72 PR;PR 55;62 57;64 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Interactions of Leu89 in PR/DRV (gray) (PDB ID 2IEN) and Met89 in PRP51-D25N/DRV (green) with neighboring residues. 2014 ACS chemical biology Figure HIV D25N 72 76 PR;PR 25;66 27;68 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Note that the wild-type PR sequence used for structural comparison includes mutations Q7K, L33I, and L63I to prevent autoproteolysis, and both proteins include C67A and C95A to eliminate potential cysteine-thiol oxidation. 2014 ACS chemical biology Figure HIV C67A;C95A;L33I;L63I;Q7K 160;169;91;101;86 164;173;95;105;89 PR 24 26 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Superposition of the monomers of PRP51-D25N/DRV (green) and wild-type PR (PDB ID 2PC0) (grey). 2014 ACS chemical biology Figure HIV D25N 39 43 PR;PR 33;70 35;72 24738918 Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps. Unique binding site for DRV in PRP51-D25N. 2014 ACS chemical biology Figure HIV D25N 37 41 PR 31 33 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. DNA amplicons spanning TDF-associated mutations K65R, K70E, and FTC-associated mutations M184V/I are generated by nested RT-PCR from plasma HIV-1 virions, representing the predominant and minor quasispecies. 2014 The Journal of infectious diseases Figure HIV K65R;K70E;M184I;M184V 48;54;89;89 52;58;96;96 RT 121 123 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. HIV-1 Log10 viral load vs the relative proportion of FTC-associated drug resistance mutations M184V (A) and M184I (B) measured by the qMVA (blue, solid lines) and 454 deep sequencing (black, dashed lines) are shown for each of 2 iPrEx participants with unrecognized infection at baseline, and randomized to FTC/TDF. 2014 The Journal of infectious diseases Figure HIV M184I;M184V 108;94 113;99 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The number of mutation sites ineligible for testing based on preestablished criteria regarding cure primer 3' end match with viral target sequence among the 131 samples possible are as follows: K65R: n = 2 (1.5%); K70E: n = 11 (8.4%); M184V: n = 5 (3.8%); and M184I: n = 4 (3.0%). 2014 The Journal of infectious diseases Figure HIV K65R;K70E;M184I;M184V 194;214;260;235 198;218;265;240 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The open symbol represents the single participant with minor variant drug resistance at the SC visit (M184I by qMVA, 0.53%). 2014 The Journal of infectious diseases Figure HIV M184I 102 108 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. (a) Reactivity of AE21 PT probed via SDS-PAGE and Western blotting: lane 1, E275C gp120 only; lane 2, mixture of E275C gp120 and KR21 PT [nonreactive peptide (Table 1)]; lane 3, mixture of E275C gp120 and MPB (commercially available thiol-specific biotinylation reagent); lane 4, mixture of E275C gp120 and AE21 PT; lane 5, biotinylated WT gp120 (positive control). 2014 Biochemistry Figure HIV E275C;E275C;E275C;E275C 76;113;189;291 81;118;194;296 gp120;gp120;gp120;gp120;gp120 82;119;195;297;340 87;124;200;302;345 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. After purification, the covalent conjugate was immobilized using amine coupling, similar to that used for E275C. 2014 Biochemistry Figure HIV E275C 106 111 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Binding of different concentrations of (a) sCD4 and (b) mAb 17b to E275C and the NeutrAvidin-captured AE21-E275C covalent conjugate, after reference subtraction and normalization to control for the amount of immobilized protein (Materials and Methods). 2014 Biochemistry Figure HIV E275C;E275C 67;107 72;112 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Binding of different concentrations of (a) sCD4, (b) mAb 17b, and (c) mAb 2G12 to E275C and the purified AE21-E275C covalent conjugate. 2014 Biochemistry Figure HIV E275C;E275C 82;110 87;115 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. E275C was immobilized on the surface using standard amine coupling (Materials and Methods). 2014 Biochemistry Figure HIV E275C 0 5 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. SDS-PAGE followed by alpha-biotin Western blot analysis of the reaction mixture containing E275C (lanes 1-6) or WT (lanes 7-12) gp120 with a fixed number of AE21-reactive peptide molecules (R1 = nAE21/ngp120 = 2, where n denotes moles) in the presence of increasing concentrations of KR21 (the nonreactive peptide). 2014 Biochemistry Figure HIV E275C 91 96 gp120 128 133 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The AE21-E275C covalent conjugate was captured from a filtered reaction mixture using surface-immobilized NeutrAvidin via the biotin handle on the peptide. 2014 Biochemistry Figure HIV E275C 9 14 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Then this peptide was conjugated to E275C gp120 through the reaction of the maleimide with the thiol group introduced on gp120 via the E275C mutation. 2014 Biochemistry Figure HIV E275C;E275C 36;135 41;140 gp120;gp120 42;121 47;126 24803853 Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. Distribution of dihedral angles in i-Pr and Et analogs bound to Y181C from REST simulations. 2014 Journal of chemical theory and computation Figure HIV Y181C 64 69 PR 37 39 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. Side chains of HIV-1 IN residues A128T and T125 in subunit 1, and E170, H171 and T174 in subunit 2 are shown. 2014 PLoS pathogens Figure HIV A128T 33 38 IN 21 23 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. MAbs b12, b6, F240, 14e, and 19b do not neutralize the corresponding BG505.T332N virus, whereas VRC01, 2G12, PG16, and PGT145 all do. 2014 Retrovirology Figure HIV T332N 75 80 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. MAbs b12, b6, F240, 14e, and 19b do not neutralize the corresponding BG505.T332N virus, whereas VRC01, 2G12, PGT123, PGT128, PG9, PG16, PGT145, and PGT151 do. 2014 Retrovirology Figure HIV T332N 75 80 24884783 Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. The infectivity of BG505.T332N pseudovirus was measured on Tzm-bl cells as luciferase activity (luminescence) after incubation with NAbs. 2014 Retrovirology Figure HIV T332N 25 30 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. (A) is the dose-effect relationship of 5 viruses (K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, K101Q and pNL4-3) in NVP. 2014 BMC infectious diseases Figure HIV H221Y;K101Q;Y181C;H221Y;K101Q;K101Q;K101Q;Y181C 62;50;56;88;69;82;95;75 67;55;61;93;74;87;100;80 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. (B) is the dose-effect relationship of 5 viruses (K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, K101Q and pNL4-3) in EFV. 2014 BMC infectious diseases Figure HIV H221Y;K101Q;Y181C;H221Y;K101Q;K101Q;K101Q;Y181C 62;50;56;88;69;82;95;75 67;55;61;93;74;87;100;80 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. (C), (D), (E) is the dose-effect relationship of K101Q/H221Y and pNL4-3 in AZT, 3TC and d4T respectively. 2014 BMC infectious diseases Figure HIV H221Y;K101Q 55;49 60;54 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. (A) Vpr S79A failed to associate with endogenous TAK1. 2014 Retrovirology Figure HIV S79A 8 12 Vpr 4 7 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. (B) HEK293T cells (4 x 106) were co-transfected with wild type TAK1 or its mutants (K34R, K158R, K209R) with or without HA-Ub DNA constructs. 2014 Retrovirology Figure HIV K158R;K209R;K34R 90;97;84 95;102;88 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. (B) Vpr S79A was unable to enhance the phosphorylation of TAK1. 2014 Retrovirology Figure HIV S79A 8 12 Vpr 4 7 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. (C) HEK293T cells (4 x 106) were transfected with 1 mug pVSV-G along with 8 mug NLENY1-ES (WT), NLENY1-DeltaVpr (DeltaVpr), or NLENY1-S79A (S79A) by PEI. 2014 Retrovirology Figure HIV S79A;S79A 140;134 144;138 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. (D) Jurkat cells (2 x 106) were infected with VSV-G pseudotyped WT, DeltaVpr, or S79A equivalent to 500 ng p24 in the presence of 5 mug/ml polybrene by spinoculation at 300 xg for 30 min. 2014 Retrovirology Figure HIV S79A 81 85 p24 107 110 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. A total of 0.5 x 106 HEK293T cells were transfected with wild type Flag-Vpr or its mutant S79A. 2014 Retrovirology Figure HIV S79A 90 94 Vpr 72 75 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. HEK293T cells (0.5 x 106) were transfected with 0.3 mug Myc-TAK1 or its mutants (K34R, K158R, K209R) along with empty vector or 0.5 mug Flag-Vpr. 2014 Retrovirology Figure HIV K158R;K209R;K34R 87;94;81 92;99;85 Vpr 141 144 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. HEK293T cells (4 x 106) were transfected with wild type Flag-Vpr or its mutant S79A. 2014 Retrovirology Figure HIV S79A 79 83 Vpr 61 64 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. HeLa cells (0.1 x 106) were transfected with Flag-Vpr or its S79A mutant along with kappaB, AP-1, or HIV-1 LTR luciferase reporter plasmid. 2014 Retrovirology Figure HIV S79A 61 65 LTR;Vpr 107;50 110;53 24912525 HIV-1 Vpr stimulates NF-kappaB and AP-1 signaling by activating TAK1. The S79A mutant of Vpr is unable to activate NF-kappaB and AP-1. 2014 Retrovirology Figure HIV S79A 4 8 Vpr 19 22 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Two days after transfection in the absence or presence of chloroquine to produce WT, N260Q or N260Q/S128N virus, HEK293T cells were stained to detect gp120 on the cell surface with the primary antibody 2G12 and a secondary anti-human antibody labelled with Alexa Fluor 647. 2014 PloS one Figure HIV N260Q;N260Q;S128N 85;94;100 90;99;105 gp120 150 155 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Western blot analysis of glycosidase-treated cell lysates derived from wild-type (WT) and mutant N260Q gp160 HIV-transfected HEK293T cells. 2014 PloS one Figure HIV N260Q 97 102 gp160 103 108 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. WT, N260Q and N260Q/S128N virus transfected HEK293T cells were lysed and subjected to WB analysis (2 ng of p24 protein), to detect gp160, gp120 and gp41 in the cell lysates. 2014 PloS one Figure HIV N260Q;N260Q;S128N 4;14;20 9;19;25 gp120;gp160;gp41;p24 138;131;148;107 143;136;152;110 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. (A) Frequencies of the I64T mutation in the Tat protein at different time points (days post Fiebig stage I/II). 2014 PloS one Figure HIV I64T 23 27 Tat 44 47 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. (A) Homology models of the p24 monomer for the sequences of the T/F virus (cyan), the T242N mutant (magenta) and the NIA mutant (green) show similar structures of the helix 6 region with modest structural differences in the neighboring N-terminal hairpin and CypA binding loop. 2014 PloS one Figure HIV T242N 86 91 p24 27 30 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. (A) The frequency of the R355K mutation in the Env352-360 T cell epitope different time points (days post Fiebig stage I/II). 2014 PloS one Figure HIV R355K 25 30 Env 47 50 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Amino acid substitutions at the I64T mutation site were highlighted in red. 2014 PloS one Figure HIV I64T 32 36 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Amino acid substitutions at the R355K mutation site were highlighted in red. 2014 PloS one Figure HIV R355K 32 37 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Impact of the V247I or G248A mutation alone on the fitness of their cognate T/F virus. 2014 PloS one Figure HIV G248A;V247I 23;14 28;19 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. No fitness costs of the early CD8+ T cell escape mutation R355K in Env. 2014 PloS one Figure HIV R355K 58 63 Env 67 70 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. No fitness costs of the early reversion mutation I64T in Tat/Rev overlapping region. 2014 PloS one Figure HIV I64T 49 53 Rev;Tat 61;57 64;60 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Partial restoration of the fitness loss of the T242N mutant by compensatory mutations. 2014 PloS one Figure HIV T242N 47 52 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Peptides containing T242N, V247I or G248A mutation alone as well as in various combinations were analyzed. 2014 PloS one Figure HIV G248A;T242N;V247I 36;20;27 41;25;32 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Relative fitness of the I64T mutant was determined by comparing to the cognate T/F virus in the single-passage assay (B) and the multiple-passage assay (C). 2014 PloS one Figure HIV I64T 24 28 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Relative fitness of the R355K mutant was determined by comparing to the cognate T/F virus in the single-passage assay (B) and the multiple-passage assay (C) as described in Figure 3. 2014 PloS one Figure HIV R355K 24 29 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The fitness impact of the V247I or G248A mutation alone was determined by comparing the mutant V247I (A and B) or G248A (C and D) to their cognate T/F virus in the single-passage assay (A and C) and the multiple-passage assay (B and D). 2014 PloS one Figure HIV G248A;G248A;V247I;V247I 35;114;26;95 40;119;31;100 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The relative fitness was determined between the T242N mutant and the NI (A and B) and NA (C and D) mutant as well as between the T/F virus and NI (E and F) or NA (G and H) mutant in the single-passage assay (left panels) and the multiple-passage assay (right panels). 2014 PloS one Figure HIV T242N 48 53 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The T242N (red) and V247I/G248A (magenta) mutations face outward in the assembly and do not occur at hexamer-hexamer interfaces. 2014 PloS one Figure HIV G248A;T242N;V247I 26;4;20 31;9;25 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. (B) Prevalence of mutations associated with nucleoside reverse-transcriptase inhibitors (NRTI), thymidine analogue mutations (TAM) and revertants, and the M184V mutation. 2014 BMC infectious diseases Figure HIV M184V 155 160 NRTI;NRTI 44;89 76;93 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. The 16 square brackets show patients in a phylogenetic cluster with bootstrap support of >70% and a mean genetic distance of <0.03 nucleotide substitutions per site; indicated patients with a K103N mutation; highlights a reference sequence. 2014 BMC infectious diseases Figure HIV K103N 193 198 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. The K103N mutation in phylogenetic analyses of HIV-1 subtype B pol sequences. 2014 BMC infectious diseases Figure HIV K103N 4 9 Pol 63 66 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (A) EFV binding to the E138D RT-T/P complex measured by fluorescence anisotropy. 2014 Nucleic acids research Figure HIV E138D 23 28 RT 29 31 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (A) NVP or (B) EFV binding to the WT and K103N RT-T/P complexes measured by fluorescence anisotropy. 2014 Nucleic acids research Figure HIV K103N 41 46 RT 47 49 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (B) dTTP binding to the K103N RT-T/P complex in the absence and presence of EFV. 2014 Nucleic acids research Figure HIV K103N 24 29 RT 30 32 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (C) dTTP binding to the K103N RT-T/P complex in the absence and presence of EFV. 2014 Nucleic acids research Figure HIV K103N 24 29 RT 30 32 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (D) FRET histograms for the WT RT-T/P complex in the absence (N = 222 traces) or presence of EFV, and for the E138D RT-T/P complex in the absence (N = 129) or presence of EFV (N = 94). 2014 Nucleic acids research Figure HIV E138D 110 115 RT;RT 31;116 33;118 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (D) Overlay of WT (1FK9) and K103N (1FKO) RT in complex with EFV. 2014 Nucleic acids research Figure HIV K103N 29 34 RT 42 44 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (E,F) PIFE traces for the K103N RT-T/P-dNTP and K103N-RT-T/P-dNTP-EFV complexes. 2014 Nucleic acids research Figure HIV K103N;K103N 26;48 31;53 RT;RT 32;54 34;56 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (G) PIFE transition histogram for the K103N-RT-T/P-dNTP-EFV complex in the absence and presence of EFV. 2014 Nucleic acids research Figure HIV K103N 38 43 RT 44 46 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (H) Average karrival and kdeparture rates extracted from 926 and 725 PIFE traces for the K103N RT-T/P-dNTP complex in the absence and presence of EFV, respectively. 2014 Nucleic acids research Figure HIV K103N 89 94 RT 95 97 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. (J) FRET histograms for K103NT RT-T/P and RT-T/P-dNTP complexes in the absence and presence of EFV (N = 178, 138, 156 and 150 individual traces, respectively). 2014 Nucleic acids research Figure HIV K103N;K103T 24;24 30;30 RT;RT 31;42 33;44 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. K103N allows the EFV-bound enzyme to form a stable polymerase-competent RT-T/P-dNTP complex. 2014 Nucleic acids research Figure HIV K103N 0 5 Pol;RT 51;72 61;74 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. K103N disrupts the salt bridge between K101 and E138. 2014 Nucleic acids research Figure HIV K103N 0 5 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. The effect of the K103N mutation, which abrogates the E138-K101 salt bridge and stabilizes the polymerase competent form of RT, is signified by a green arrow. 2014 Nucleic acids research Figure HIV K103N 18 23 Pol;RT 95;124 105;126 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. Only E138K resulted in a decrease in the proportion of infected cells (*); (C) Relative proportion of GFP-expressing reporter proviruses that became reactivated following TNFalpha treatment. 2014 Viruses Figure HIV E138K 5 10 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. (A) HeLa cells were transfected with p R PR- HIV-1 constructs directing the expression of either wt Gag, the p6 S40F, S40N, S40D or PTAP mutants or the MA G2A mutant. 2014 Viruses Figure HIV G2A;S40D;S40N 156;124;118 159;128;122 Gag;Gag;Matrix;PR 100;109;153;41 103;111;155;43 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. (A) HeLa-Kb cells were transfected with syngag expression constructs coding for Gag-SL, DeltaPTAP-SL, S40F-SL and S40F/DeltaPTAP-SL. 2014 Viruses Figure HIV S40F;S40F 102;114 106;118 Gag 80 83 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. (A) Structure of sp6(23-52)S40F determined by NMR spectroscopy. 2014 Viruses Figure HIV S40F 27 31 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Chemical shift differences (ppm) of the alpha-protons between the experimental values and those for residues in a random coil for the C-terminal peptides sp6(23-52) wt and the mutants sp6(23-52)S40F, sp6(23-52)S40D and sp6(23-52)S40N in 50% aqueous TFE at pH 3. 2014 Viruses Figure HIV S40D;S40F;S40N 210;194;229 214;198;233 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Gag was recovered from whole cell lysates by immunoprecipitation using anti-HIV antibodies, and ubiquitinated species were detected by anti-HA staining; (D) Activation of B3Z hybridoma T cells was assessed by a colorimetric beta-galactosidase assay after overnight cocultivation with HeLa-Kb cells expressing Gag wt, Gag-SL wt, DeltaPTAP-SL, S40F-SL or S40F/DeltaPTAP-SL in various effector-to-target ratios. 2014 Viruses Figure HIV S40F;S40F 342;353 346;357 Gag;Gag;Gag 0;309;317 3;312;320 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. HeLa cells were co-transfected with HA-ubiquitin and either p R PR- plasmids (A) or syngag plasmids encoding for either wt Gag, or the p6 mutant S40F or PTAP, respectively (B). 2014 Viruses Figure HIV S40F 145 149 Gag;Gag;PR 123;135;64 126;137;66 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. HeLa cells were transfected with the env-deleted HIV-1 expression plasmid pNLenv1, as wt or S40F mutant, and lysed under conditions where the 26S proteasome and ubiquitin hydrolases were inhibited. 2014 Viruses Figure HIV S40F 92 96 Env 37 40 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Influence of the S40N, S40D or S40A mutation on Gag ubiquitination. 2014 Viruses Figure HIV S40A;S40D;S40N 31;23;17 35;27;21 Gag 48 51 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. NMR structure of p6(23-52)S40F confirms formation of a new hydrophobic domain. 2014 Viruses Figure HIV S40F 26 30 Gag 17 19 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Shorter exposures of the Western blots revealing the delay in CA processing for the S40F mutant are depicted in the lower panels (C). 2014 Viruses Figure HIV S40F 84 88 Capsid 62 64 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F mediated ubiquitination of Gag occurs irrespective of Gag processing or other viral proteins. 2014 Viruses Figure HIV S40F 4 8 Gag;Gag 36;63 39;66 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F mutation in p6 augments Gag ubiquitination. 2014 Viruses Figure HIV S40F 4 8 Gag;Gag 33;21 36;23 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F mutation increases selectively the membrane association of Pr55. 2014 Viruses Figure HIV S40F 4 8 PR 68 70 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The S40F mutation induces an enhanced MHC-I antigen presentation of Gag derived epitopes. 2014 Viruses Figure HIV S40F 4 8 Gag 68 71 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. p24 production in MT2 cells after infection by G367R virus pseudotyped with VSV-G viruses in the presence of endocytosis inhibitors. 2014 Virology journal Figure HIV G367R;G367R 48;47 53;52 p24 0 3 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. p24 production in MT2 cells after infection by G367R virus pseudotyped with VSV-G viruses in the presence of entry inhibitors. 2014 Virology journal Figure HIV G367R;G367R 48;47 53;52 p24 0 3 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. p24 production in MT2 cells after infection by G367R virus pseudotyped with VSV-G, G367R or wild type viruses. 2014 Virology journal Figure HIV G367R;G367R;G367R;G367R 48;84;47;83 53;89;52;88 p24 0 3 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. p24 production in MT2-MT4 cell cocultures after infection by G367R pseudotyped with VSV-G viruses. 2014 Virology journal Figure HIV G367R;G367R 62;61 67;66 p24 0 3 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. p24 production in MT2, MT4 and SupT1 cells after infection by G367R virus that had been pseudotyped with VSV-G viruses in the presence of IL2, PMA or ionomycin. 2014 Virology journal Figure HIV G367R;G367R 63;62 68;67 p24 0 3 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. p24 production in MT2, MT4, SupT1 and PM-1 cells after infection by G367R virus pseudotyped with VSV-G. 2014 Virology journal Figure HIV G367R;G367R 69;68 74;73 p24 0 3 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Association between M184I/V mutation and emtricitabine over the time interval 2005-2011, controlling for lamivudine, was estimated using the multivariate logistic regression model: logit(PM184)~beta0 + beta1 x 3TC + beta2 x FTC. 2014 PloS one Figure HIV M184I;M184V 20;20 27;27 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Temporal trends of lamivudine (3TC) or emtricitabine (FTC)-containing prescriptions (black) with the frequency of the M184I/V mutation (red). 2014 PloS one Figure HIV M184I;M184V 118;118 125;125 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. The slope parameter beta2 represents the log odds ratio for the change in M184I/V frequency associated with a one unit. 2014 PloS one Figure HIV M184I;M184V 74;74 81;81 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. (A) Top: Site-directed mutagenesis using oligonucleotide is shown using K103N as an example. 2014 PloS one Figure HIV K103N 72 77 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. wild type; 2, M41L-TTG; 3, M41L-CTG; 4, K65R-AGA; 5, 70R-AGA; 6, 70R-AGG; 7, wild type; 8, 103N-AAC; 9, K103N-AAT; 10, M184V-GTG; 11, T215Y-TAC; 12, T215F-TTC. 2014 PloS one Figure HIV K103N;K65R;M184V;M41L;M41L;T215F;T215Y 104;40;119;14;27;149;134 109;44;124;18;31;154;139 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Detection frequency of mutant K103N and Y181C minority variants. 2014 PloS one Figure HIV K103N;Y181C 30;40 35;45 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. In presence of K103N-AAC (A1) and K103-AAT (A2) mutants, only the specific mutant amplicons will be amplified when using mutant specific forward (MSFP) and a common reverse primer (CRP), respectively. 2014 PloS one Figure HIV K103N 15 20 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Mutant specific (Sp) and non-specific (NSp) standard curves of K103N AAC allele (B1), K103N AAT allele (B2) and Y181C TGT allele (B3) are in parallel with each experiment. 2014 PloS one Figure HIV K103N;K103N;Y181C 63;86;112 68;91;117 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Ninety-two treatment naive HIV patients plasma were analysed by allele-specific PCR, detecting the two major NNRTI mutations K103N and Y181C in the reverse transcriptase gene. 2014 PloS one Figure HIV K103N;Y181C 125;135 130;140 RT;NNRTI 148;109 169;114 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The limit of detection for the Y181C mutation (TGT) is indicated by a solid line. 2014 PloS one Figure HIV Y181C 31 36 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Comparison of binding of tenofovir diphosphate (TFV-DP) and dATP to K65R RT dsDNA. 2014 Viruses Figure HIV K65R 68 72 RT 73 75 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Schematic of dislocation mutagenesis and the development of the K65R mutation in subtype C HIV-1. 2014 Viruses Figure HIV K65R 64 68 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Shown is stacking of the guanidinium plane of Arg65 and guanidinium plane of Arg72 and adenine base in K65R RT dsDNA dATP (B) and K65R RT dsDNA TFV-DP (C) ternary structures. 2014 Viruses Figure HIV K65R;K65R 103;130 107;134 RT;RT 108;135 110;137 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. Step 1: DNA synthesis approaches the end of a homopolymeric nt stretch that ends precisely at the location of K65R development. 2014 Viruses Figure HIV K65R 110 114 25341667 The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance. This series of events yields the AAG-to-AGG change that is responsible for the more facilitated appearance of the K65R mutation in subtype C HIV-1. 2014 Viruses Figure HIV K65R 114 118 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. a and b represent interactions between S/A138 and NHR residues in N43D single mutant and N43D/S138A double mutant. 2014 PloS one Figure HIV N43D;N43D;S138A 66;89;94 70;93;99 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Comparisons of backbone atoms RMSF in inhibitor C34 of wild type and N43D mutant. 2014 PloS one Figure HIV N43D 69 73 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Interactions between CHR (C34) and NHR for N43D and N43D/S138A mutant. 2014 PloS one Figure HIV N43D;N43D;S138A 43;52;57 47;56;62 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Interactions between residue S/A138 and NHR for N43D and N43D/S138A mutant. 2014 PloS one Figure HIV N43D;N43D;S138A 48;57;62 52;61;67 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Per-residue differential (N43D/S138A double mutant minus N43D single mutant) footprints for receptor (kcal/mol). 2014 PloS one Figure HIV N43D;N43D;S138A 26;57;31 30;61;36 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Per-residue differential in DeltaEelec term for inhibitor C34 of wild type and N43D mutant (kcal/mol). 2014 PloS one Figure HIV N43D 79 83 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Per-residue differential in van der Waals for inhibitor C34 of N43D mutant and N43D/S138A double mutant (kcal/mol). 2014 PloS one Figure HIV N43D;N43D;S138A 63;79;84 67;83;89 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Structures of N43D mutant (blue) and N43D/S138A double mutant (white). 2014 PloS one Figure HIV N43D;N43D;S138A 14;37;42 18;41;47 25393106 Molecular dynamics studies of the inhibitor C34 binding to the wild-type and mutant HIV-1 gp41: inhibitory and drug resistant mechanism. Structures of wild type (white) and N43D mutant (blue). 2014 PloS one Figure HIV N43D 36 40 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. (a) The frequency of the T242N escape mutation in the TW10 epitope was determined by comparing the longitudinal sequences to the CH131 T/F sequence. 2014 Retrovirology Figure HIV T242N 25 30 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. (b) The N242T reversion mutation and I247V mutation were introduced into the CH131 T/F viral genome and the replication kinetics of the mutants and their corresponding T/F virus were determined by measuring p24 concentrations in the cell culture supernatants. 2014 Retrovirology Figure HIV I247V;N242T 37;8 42;13 p24 207 210 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. (c) The relative fitness of the T242N reversion mutant was determined by comparing to the corresponding T/F virus by the PASS fitness assay. 2014 Retrovirology Figure HIV T242N 32 37 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. (d) The fitness cost of the T242N mutant was determined by comparing the I247V mutant that contained the T242N mutation but not the compensatory isoleucine at position 247 to the T/F virus. 2014 Retrovirology Figure HIV I247V;T242N;T242N 73;28;105 78;33;110 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Association of the T242N mutation with the viral load. 2014 Retrovirology Figure HIV T242N;T242N 20;19 25;24 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. CH131 was infected with the T242N escape mutant. 2014 Retrovirology Figure HIV T242N 28 33 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Fitness impact of the T242N mutation and its compensatory amino acid in the transmitted T242N escape mutant. 2014 Retrovirology Figure HIV T242N;T242N;T242N;T242N 23;89;22;88 28;94;27;93 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. Fitness loss caused by the T242N mutation was partially restored by the preexisting compensatory amino acids. 2014 Retrovirology Figure HIV T242N;T242N 28;27 33;32 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. No T242N mutation was detected in CH40 and CH470. 2014 Retrovirology Figure HIV T242N 3 8 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The increased fitness loss of the T242N mutants after removing the compensatory amino acids was determined for CH58 (d), CH470 (e), and CH40 (f) by comparing each double-mutation virus to its corresponding T/F virus. 2014 Retrovirology Figure HIV T242N 34 39 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The relative fitness of the T242N mutants was determined for CH58 (a), CH470 (b), and CH40 (c) by comparing each T242N mutant to its corresponding T/F virus. 2014 Retrovirology Figure HIV T242N;T242N 28;113 33;118 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The T cell escape mutation T242N was selected in vivo in subjects CH77 and CH58. 2014 Retrovirology Figure HIV T242N 27 32 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The T242N escape mutation and compensatory amino acids were introduced into the CH58 (d), CH470 (e), and CH40 (f) T/F viral genomes. 2014 Retrovirology Figure HIV T242N 4 9 25407514 Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation. The time for the first detection of the T242N escape mutation (blue and brown) or the N242T reversion mutation (red) is indicated by open triangle and the time for the fixation of the T242N or N242T mutation in the viral population is indicated by solid triangle. 2014 Retrovirology Figure HIV N242T;N242T;T242N;T242N 86;193;40;184 91;198;45;189 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. (A) p24 production of HIV-1NL4-3 and HIV-1NL4-3(H171T IN) plotted as percent WT with standard deviations shown for n = 3 independent experiments. 2014 Retrovirology Figure HIV H171T 48 53 p24;IN 4;54 7;56 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. (B) Quantitation of counted virions (100 for WT or H171T per experiment). 2014 Retrovirology Figure HIV H171T 51 56 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. (B) Single round infection of HIV-1NL4-3 and HIV-1NL4-3(H171T IN) determined by luciferase expression and plotted as percent WT infectivity with standard deviations shown for three independent experiments. 2014 Retrovirology Figure HIV H171T 56 61 IN 62 64 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. (C) SEC of WT and H171T INs. 2014 Retrovirology Figure HIV H171T 18 23 IN 24 27 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. (D) HTRF-based LEDGF/p75 independent integration assay and (E) HTRF-based LEDGF/p75 dependent integration assays showing stimulation of WT and H171T IN activities at indicated LEDGF/p75 concentrations. 2014 Retrovirology Figure HIV H171T 143 148 IN 149 151 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. (F) HTRF-based assays to determine LEDGF/p75 binding affinities for WT (opened boxes) or H171T (closed circles) INs. 2014 Retrovirology Figure HIV H171T 89 94 IN 112 115 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. BI-D treatments include (A) WT IN +0.120 muM BI-D, (B) H171T IN +0.120 muM BI-D, (C) WT IN +10 muM BI-D and (D) H171T IN +10 muM BI-D. 2014 Retrovirology Figure HIV H171T;H171T 53;110 60;117 IN;IN;IN;IN 31;61;88;118 33;63;90;120 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Concentration dependent effects of BI-D on viral core morphology for HIV-1 NL4-3 and HIV-1 NL4-3(H171T IN) . 2014 Retrovirology Figure HIV H171T;H171T 98;97 103;102 IN 103 105 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Crystal structures of BI-D bound to WT and H171T CCD dimers. 2014 Retrovirology Figure HIV H171T;H171T 44;43 49;48 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. DLS analysis of BI-D induced oligomerization of recombinant WT and the H171T INs. 2014 Retrovirology Figure HIV H171T;H171T 72;71 77;76 IN 77 80 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Effects of the H171T IN substitution on HIV-1 replication and recombinant IN activities. 2014 Retrovirology Figure HIV H171T;H171T 16;15 21;20 IN;IN 21;74 23;76 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Panel A is the H171T CCD dimer and panel B is the WT CCD dimer. 2014 Retrovirology Figure HIV H171T 15 20 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. SPR analysis of BI-D interactions with WT and H171T mutant IN CCDs. 2014 Retrovirology Figure HIV H171T;H171T 47;46 52;51 IN 59 61 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. SPR binding kinetics for BI-D interactions with (A) WT IN CCD and (B) H171T IN CCD at indicated inhibitor concentrations. 2014 Retrovirology Figure HIV H171T 68 75 IN;IN 55;76 57;78 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The arrow indicates the hydrogen bond between the protonated Ndelta- on His171 and the ether oxygen on the tert-butoxy (B), which is absent in the H171T IN CCD structure (A). 2014 Retrovirology Figure HIV H171T 147 152 IN 153 155 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Analysis of gp120 levels in the viral envelope of WT and mutant N616Q gp41 virus strains. 2014 Retrovirology Figure HIV N616Q;N616Q 65;64 70;69 Env;gp120;gp41 38;12;70 46;17;74 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Infectivity of HIV-1 NL4.3 mutants containing the N674D mutation or a combination of gp41 glycan deletions. 2014 Retrovirology Figure HIV N674D;N674D 51;50 56;55 gp41 85 89 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The cytopathic effect of WT and mutant N616Q gp41 virus strains. 2014 Retrovirology Figure HIV N616Q;N616Q 40;39 45;44 gp41 45 49 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The HIV-1HXB2 amino acid numbering was used (N616Q), which corresponds to N614Q in HIV-1NL4.3, N616Q in HIV-1IIIB, N603Q in HIV-1HE and N628Q in HIV-1ADA. 2014 Retrovirology Figure HIV N603Q;N614Q;N616Q;N616Q;N628Q 115;74;45;95;136 120;79;50;100;141 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. A-B: DCs were infected with 17.5 ng p24 HIV-WT or HIV-M184T. 2014 Retrovirology Figure HIV M184T 54 59 p24 36 39 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Abbreviations: WT: HIV-WT, M184V: HIV-M184V, M184I: HIV-M184I, M184T: HIV-M184T, K103N: HIV-K103N, n.c.: no infection control. 2014 Retrovirology Figure HIV K103N;K103N;M184I;M184I;M184T;M184T;M184V;M184V 81;92;45;56;63;74;27;38 86;97;50;61;68;79;32;43 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. At 2, 6, 24 and 72 hours post infection (hpi), the relative presence of HIV-WT (green, horizontal stripes) and HIV-M184T (red, checkered) were determined by population sequencing. 2014 Retrovirology Figure HIV M184T 115 120 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Detailed analysis of replication capacity of HIV-M184T in DCs. 2014 Retrovirology Figure HIV M184T;M184T 50;49 55;54 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. HIV infection of LCs (A) or DCs (B) by a panel of HIV-1 drug resistance variants (M184V, -I, -T and K103N) was measured after six days. 2014 Retrovirology Figure HIV K103N;M184V 100;82 105;87 HIV infections 0 13 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. M184T. 2014 Retrovirology Figure HIV M184T 0 5 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (A) PRWT-SQV is shown in silver and PRG48T/L89M-SQV is shown in cyan and magenta. 2015 Biochemistry Figure HIV L89M 43 47 PR 36 38 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (A) Superposition of PRG48T/L89M-SQV (cyan) with PRWT-SQV (1HXB) (silver). 2015 Biochemistry Figure HIV L89M 28 32 PR 21 23 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (A) Superposition of the "flap" region of PRG48T/L89M-SQV (cyan/orange) and PRWT-SQV (silver). 2015 Biochemistry Figure HIV L89M 49 53 PR 42 44 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (B) Superposition of PRG48T/L89M-SQV (cyan) with PRWT-SQV (silver). 2015 Biochemistry Figure HIV L89M 28 32 PR 21 23 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (B) The root mean squared fluctuations of the Calpha atoms of PRWT-SQV and PRG48T/L89M-SQV. 2015 Biochemistry Figure HIV L89M 82 86 PR 75 77 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (C) Crystal structure of PRG48T/L89M-SQV (cyan) superposed with PRWT-SQV (1HXB) (silver). 2015 Biochemistry Figure HIV L89M 32 36 PR 25 27 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (C) DeltaRMSF values in (B) mapped onto PR illustrating where the largest differences between PRWT-SQV and PRG48T/L89M-SQV occur. 2015 Biochemistry Figure HIV L89M 114 118 PR;PR 40;107 42;109 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (C) Surface representation of PRG48T/L89M-SQV. 2015 Biochemistry Figure HIV L89M 37 41 PR 30 32 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. (Red signifies residues that are less flexible in PRG48T/L89M-SQV compared to PRWT-SQV. 2015 Biochemistry Figure HIV L89M 57 61 PR 50 52 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. A positive number indicates that a particular residue of PRWT-SQV fluctuates more than PRG48T/L89M-SQV and vice versa. 2015 Biochemistry Figure HIV L89M 94 98 PR 87 89 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In monomer A of PRG48T/L89M-SQV, hydrogen bonds between Gln18 and Gly16, as well as between Gln18 and Ser37 are lost resulting in approximately 1.5 and 2 A displacement of the 'teens and 30's strand, respectively. 2015 Biochemistry Figure HIV L89M 23 27 PR 16 18 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In PRG48T/L89M-SQV, the side chain of Val82' is relocated 156 away from the P1 Phe of saquinavir and the guinidinium group of Arg8' is rotated 117 away from the active site. 2015 Biochemistry Figure HIV L89M 10 14 PR 3 5 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In PRG48T/L89M-SQV, there is a new hydrogen bonding interaction between the carbonyl oxygen of Ser37' and the Nepsilon of Gln18'. 2015 Biochemistry Figure HIV L89M 10 14 PR 3 5 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In PRWT-SQV, vdw interactions are amenable for hydrophobic sliding; however, in PRG48T/L89M-SQV a redistribution of vdw forces results in altered strand interactions and modified hydrophobic sliding. 2015 Biochemistry Figure HIV L89M 87 91 PR 80 82 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Monomer B of PRG48T/L89M-SQV exhibits a greater displacement in the 'teens region (2.5 A) and smaller displacement in the 30's strand (1.25 A) compared to monomer A. 2015 Biochemistry Figure HIV L89M 20 24 PR 13 15 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. PRG48T/L89M-SQV residues are rendered as dark red sticks and PRWT-SQV as silver sticks. 2015 Biochemistry Figure HIV L89M 7 11 PR 0 2 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Repositioning of the flap of monomer B of PRG48T/L89M-SQV is stabilized by new vdw interactions between Phe53' and Thre48'. 2015 Biochemistry Figure HIV L89M 49 53 PR 42 44 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Stereo images of hydrophobic core residues in monomer B of (A) PRWT-SQV and (B) PRG48T/L89M-SQV. 2015 Biochemistry Figure HIV L89M 87 91 PR 80 82 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The differences between the RMSF values of the PRWT-SQV and PRG48T/L89M-SQV were calculated. 2015 Biochemistry Figure HIV L89M 67 71 PR 60 62 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The repositioning of Val82' and Arg8' results in the opening of the base of the S1/S3 subsite in the PRG48T/L89M-SQV structure and results in the loss of three vdw contacts between the P1 Phe of SQV and S1 of PRG48T/L89M-SQV. 2015 Biochemistry Figure HIV L89M;L89M 108;216 112;220 PR;PR 101;209 103;211 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. There is an increase in distance between the side chains of Ile54 and Gly51' in PRG48T/L89M-SQV compared to PRWT-SQV resulting in a loss of a vdw interaction between the flaps of monomer A and B in PRG48T/L89M-SQV. 2015 Biochemistry Figure HIV L89M;L89M 87;205 91;209 PR;PR 80;198 82;200 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Vdw contacts are also lost between Gly51 and Gly52' and between between Ile50 and Thre48' in PRG48T/L89M-SQV. 2015 Biochemistry Figure HIV L89M 100 104 PR 93 95 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Vdw interactions and distances are shown in red for PRG48T/L89M-SQV and gray for PRWT-SQV. 2015 Biochemistry Figure HIV L89M 59 63 PR 52 54 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Vdw interactions are shown as dashed lines for PRG48T/L89M-SQV (red) and PRWT-SQV (gray). 2015 Biochemistry Figure HIV L89M 54 58 PR 47 49 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Yellow signifies residues that are more flexible in the PRG48T/L89M-SQV relative to PRWT-SQV. 2015 Biochemistry Figure HIV L89M 63 67 PR 56 58 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Yellow spheres indicate the locations of the mutations Gly48Thre and Leu89Met. 2015 Biochemistry Figure HIV G48T;L89M 55;69 63;77 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). (A) Replication kinetics of HIV-1NL4-3uncwt, FL, FL-N40S, and NL4-3 late(-). 2014 Retrovirology Figure HIV N40S 52 56 25524645 Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag). (B) Replication kinetics of HIV-1NL4-3uncwt, S40N, and S40F. 2014 Retrovirology Figure HIV S40F;S40N 55;45 59;49 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. B cell responses after the immunization by HIV-1 Env gp120 and W427S mutant. 2014 PloS one Figure HIV W427S 63 68 gp120;Env 53;49 58;52 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. WT depict the mice from 06044 WT group and M depict the mice from W427S group. 2014 PloS one Figure HIV W427S 66 71 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. A: The conformational sampling of WT (left) and M36I (right) PR in complex with RH-IN substrate was projected along the first two principal components fore each transient conformer. 2014 BMC genomics Figure HIV M36I 48 52 IN;PR 83;61 85;63 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. B: the free energy landscape (FEL) analysis and representative structures from the WT (left) and M36I (right) MD trajectories. 2014 BMC genomics Figure HIV M36I 97 101 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. Right: Time evolution of the volume of the main cavity (active site) during the MD simulations of the WT and M36I, in complex with the different ligands, colored as Fig.2. 2014 BMC genomics Figure HIV M36I 109 113 25573486 Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics. The wild type enzyme (WT-PR) is represented in black and the mutant (M36I) in red. 2014 BMC genomics Figure HIV M36I 69 73 PR 25 27 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In all experiments, control viruses HIV-M184V, -M184I and -M184T and wild type (WT) HIV were used as reference viruses. 2014 Retrovirology Figure HIV M184I;M184T;M184V 48;59;40 53;64;45 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. RC of WT and control viruses (A, D) is indicated in the corresponding graphs by a square, and the range in RC of WT and M184T by the grey area. 2014 Retrovirology Figure HIV M184T 120 125 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. (A) Representative gel showing the cleavage of the PPT17r8d strand in the template-primer T57d/PPT17r8d complex (sequence given below) obtained with the WT RT and mutants N348I, T369I and N348I/T369I. 2015 Nucleic acids research Figure HIV N348I;N348I;T369I;T369I 171;188;178;194 176;193;183;199 RT 156 158 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. (B) RNase H activity of WT, N348I/T369I and N348I mutant enzymes on a PPT29DNA/PPT17r complex. 2015 Nucleic acids research Figure HIV N348I;N348I;T369I 28;44;34 33;49;39 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Effects of NNRTIs on PPT susceptibility to RNase H cleavage by WT and mutant N348I/T369I RTs. 2015 Nucleic acids research Figure HIV N348I;T369I 77;83 82;88 NNRTI;RT 11;89 17;92 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Graphical representations of the results obtained with WT and mutant N348I/T369I RTs are shown on the right. 2015 Nucleic acids research Figure HIV N348I;T369I 69;75 74;80 RT 81 84 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. In reactions carried out with WT RT aliquots were taken 20 s after adding the template-primer, while in the case of the N348I/T369I RT time points were collected 60 s after adding the PPT29DNA/PPT17r complex. 2015 Nucleic acids research Figure HIV N348I;T369I 120;126 125;131 RT;RT 33;132 35;134 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. WT, N348I and/or N348I/T369I RTs (50 nM) were mixed with 25-nM template-primer (T57d/PPT17r8d), and RNase H cleavage was monitored in the absence or presence of drug. 2015 Nucleic acids research Figure HIV N348I;N348I;T369I 4;17;23 9;22;28 RT 29 32 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Orientational correlation of protease residues' fluctuations of NC-p1V82A and AP2VNC-p1V82A to those of NC-p1WT in the first (A) and second (D) slowest modes. 2015 Evolutionary applications Figure HIV V82A;V82A 69;87 73;91 PR;NC;NC 29;64;104 37;66;106 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Orientational correlation of protease residues' fluctuations of NC-p1WT, NC-p1V82A, and AP2VNC-p1V82A to those of the averaged wild-type natural substrate complexes other than NC-p1 in the first (A) and second (D) slowest modes. 2015 Evolutionary applications Figure HIV V82A;V82A 78;97 82;101 PR;NC;NC;NC 29;64;73;176 37;66;75;178 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Orientational correlation of the protease residues' fluctuations of p1-p6D30N, p1-p6D30N/N88D, and LP1'Fp1-p6D30N/N88D to those of p1-p6WT in the first (A) and second (D) slowest modes. 2015 Evolutionary applications Figure HIV D30N;D30N;D30N;N88D;N88D 73;84;109;89;114 77;88;113;93;118 PR;Gag;Gag;Gag 33;71;82;107 41;73;84;109 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The residues that display the maximum variations between the directions of fluctuations are color coded according to the change in the correlation of NC-p1WT and AP2VNC-p1V82A compared to the averaged wild-type natural substrate complexes other than NC-p1; (B) and (C) in the first slowest mode, and (E) and (F) in the second slowest mode, respectively. 2015 Evolutionary applications Figure HIV V82A 171 175 NC;NC 150;250 152;252 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The residues that display the maximum variations between the directions of fluctuations are color coded according to the change in the correlations of NC-p1V82A and AP2VNC-p1V82A compared to NC-p1WT; (B) and (C) in the first slowest mode, and (E) and (F) in the second slowest mode, respectively. 2015 Evolutionary applications Figure HIV V82A;V82A 156;174 160;178 NC;NC 151;191 153;193 25685193 Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. The residues that display the maximum variations between the directions of fluctuations are color coded according to the change in the correlations of p1-p6D30N/N88D and LP1'Fp1-p6D30N/N88D compared to p1-p6WT; (B) and (C) in the first slowest mode, and (E) and (F) in the second slowest mode, respectively. 2015 Evolutionary applications Figure HIV D30N;D30N;N88D;N88D 156;180;161;185 160;184;165;189 Gag;Gag 154;178 156;180 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. (A) RT (WT):1; (B) RT (Y181C):1; (C) RT (K103N/Y181C):l; (D) RT (WT):2; (E) RT (Y181C):2; and (F) RT (K103N/Y181C):2. 2015 Journal of medicinal chemistry Figure HIV K103N;K103N;Y181C;Y181C;Y181C;Y181C 41;102;23;47;80;108 46;107;28;52;85;113 RT;RT;RT;RT;RT;RT 4;19;37;61;76;98 6;21;39;63;78;100 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. (B) RT (Y181C) (light green) in complex with 1 (pink) aligned with RT (Y181C) (darker green) in complex with 2 (purple). 2015 Journal of medicinal chemistry Figure HIV Y181C;Y181C 8;71 13;76 RT;RT 4;67 6;69 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. (C) RT (K103N/Y181C) (gold) in complex with 1 (pink) aligned with RT (K103N/Y181C) (yellow) in complex with 2 (purple). 2015 Journal of medicinal chemistry Figure HIV K103N;K103N;Y181C;Y181C 8;70;14;76 13;75;19;81 RT;RT 4;66 6;68 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Compound 2 maintains the same aag conformation in all of the structures; two hydrogen bonds with residues Lys103 and Pro236 are maintained in the RT (Y181C):2 and RT (K103N/Y181C:2 structures. 2015 Journal of medicinal chemistry Figure HIV K103N;Y181C;Y181C 167;150;173 172;155;178 RT;RT 146;163 148;165 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Ethoxy uracil conformation of compounds 1 and 2 in the RT (WT) [teal], RT (Y181C) [light green], and RT (K103N/Y181C) [gold] crystal structures. 2015 Journal of medicinal chemistry Figure HIV K103N;Y181C;Y181C 105;75;111 110;80;116 RT;RT;RT 55;71;101 57;73;103 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. RT (WT) structures are illustrated in teal, RT (Y181C) structures are illustrated in light green, and RT (K103N/Y181C) structures are illustrated in gold. 2015 Journal of medicinal chemistry Figure HIV K103N;Y181C;Y181C 106;48;112 111;53;117 RT;RT;RT 0;44;102 2;46;104 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The sag conformation and rotation of the uracil in the RT (Y181C):1 and RT (K103N/Y181C):1 causes the loss of hydrogen bonds in the mutant structures. 2015 Journal of medicinal chemistry Figure HIV K103N;Y181C;Y181C 76;59;82 81;64;87 RT;RT 55;72 57;74 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Nucleotide sequence showing D67N and K70R and the single nucleotide changes resulting in K65K and K66K. 2015 Nucleic acids research Figure HIV D67N;K65K;K66K;K70R 28;89;98;37 32;93;102;41 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. The D67N and K70R mutations are shown in green. 2015 Nucleic acids research Figure HIV D67N;K70R 4;13 8;17 25808007 In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. (B) and (C) Representative dose-response profiles for WT, E92Q + N155H, G140S + Q148R and T97A + Y143C HIV-2ROD9. 2015 Retrovirology Figure HIV E92Q;G140S;N155H;Q148R;T97A;Y143C 58;72;65;80;90;97 62;77;70;85;94;102 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. (C) black: RTshort-mt4-T345S without ATP; red: 355 muM RTshort-mt4-T345S with a 59 fold ATP excess. 2015 Retrovirology Figure HIV T345S;T345S 23;67 28;72 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. HSQC spectra of RTshort-WT, RTshort- mt4 and RTshort- mt4 -T345S . 2015 Retrovirology Figure HIV T345S;T345S 60;59 65;64 25808094 AZT resistance alters enzymatic properties and creates an ATP-binding site in SFVmac reverse transcriptase. Only the p-value of E350K <= 0.01 (**) represents a statistically significant difference to the WT protein. 2015 Retrovirology Figure HIV E350K 20 25 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. (E, F) Intraepitope HIV-1 polymorphisms for (E) TL9-p24 shown on the X-axis for Q182X as peptide position 3 and T186S as position 7 and (F) for RM9-Nef R71K as for peptide position 1 and L76X as position 6 and expressed as the percentage of total viral sequences for n = 1,327 HIV-1 infected individuals of which n = 189 expressed HLA-B*07:02, n = 436 expressed HLA-B*42:01, n = 56 expressed HLA-B*42:02 and n = 213 expressed HLA-B*81:01. 2015 Retrovirology Figure HIV R71K;T186S 152;112 156;117 p24;Nef 52;148 55;151 HIV infections 277 291 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. In (C), recombinant HIV-1 bearing wt or S375W Envs was incubated on ice for different amounts of time. 2015 PloS one Figure HIV S375W 40 45 Env 46 50 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Insights into the I559P phenotypes from the structure of the soluble gp140 SOSIP.664 Env trimer. 2015 PloS one Figure HIV I559P 18 23 gp140;Env 69;85 74;88 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Ligand binding to HIV-1BG505 full-length wild-type and I559P Env variants. 2015 PloS one Figure HIV I559P 55 60 Env 61 64 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Normalized amounts of recombinant luciferase-expressing HIV-1 pseudotyped with the wt and S375W HIV-1BG505 Envs were incubated at 37 C with increasing concentrations (0-200 nM) of sCD4 (A) or VRC01 (B) for 1 hr prior to addition of Cf2Th-CD4/CCR5 cells. 2015 PloS one Figure HIV S375W 90 95 Env 107 111 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The binding of wild-type (wt) and I559P HIV-1BG505 Env full-length (gp160) variants expressed on the cell surface was measured by cell-based ELISA, and is plotted relative to the binding of the 2G12 antibody. 2015 PloS one Figure HIV I559P 34 39 gp160;Env 68;51 73;54 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. the frequency of G190A with treatment duration; c. 2014 AIDS research and therapy Figure HIV G190A 17 22 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. the frequency of K103N with treatment duration; b. 2014 AIDS research and therapy Figure HIV K103N 17 22 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. the frequency of Y181C with treatment duration. 2014 AIDS research and therapy Figure HIV Y181C 17 22 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. (A) Resistance profile of HIV WT and HIV M184V in GHOST cells in the presence of 3TC; (B) GHOST cells were infected with HIV WT and HIV M184V in the presence of emetine. 2015 Molecules (Basel, Switzerland) Figure HIV M184V;M184V 41;136 46;141 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. (A) Resistance profile of HIV WT and HIV M184V in PBMCs in the presence of 3TC; (B) Phenotypic assays of HIV viruses (WT and M181V) with emetine; (C) Cytotoxicity effects of emetine in PBMCs. 2015 Molecules (Basel, Switzerland) Figure HIV M181V;M184V 125;41 130;46 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Emetine inhibits HIV wild type and HIV M184V infectivity in PBMCs. 2015 Molecules (Basel, Switzerland) Figure HIV M184V 39 44 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Emetine inhibits HIV wild type and HIV M184V replication in GHOST Cells. 2015 Molecules (Basel, Switzerland) Figure HIV M184V 39 44 26111177 Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. Peripheral blood mononuclear cells were isolated from HIV-negative blood donors and infected with HIV WT or HIV M184V and seeded in the presence of an antiretroviral. 2015 Molecules (Basel, Switzerland) Figure HIV M184V 112 117 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. K103N and Y181C were the most frequent NVP RAM (24.2% and 22.7% of the samples, respectively). 2015 PloS one Figure HIV Y181C;K103N 10;0 15;5 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. b The ability of ROD10 Env to bind tetherin mutant A100D was investigated by co-IP in 293T cells, using a GFP-tagged ROD10 Env. 2015 Retrovirology Figure HIV A100D 51 56 Env;Env 23;123 26;126 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. T215Y/F and T215Rev are shown in green but were taken together (T215) for the linear regression. 2015 AIDS (London, England) Figure HIV T215F;T215Y 0;0 7;7 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. (A) Analysis of K103N populations in Individual 3: Solid and open circles indicate K103N positive and negative bulk sequence results, respectively. 2015 PloS one Figure HIV K103N;K103N 16;83 21;88 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. (B) Analysis of T215I populations in Individual 3: Solid and open circles indicate T215I positive and negative bulk sequence results, respectively. 2015 PloS one Figure HIV T215I;T215I 16;83 21;88 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. (C) Analysis of K103N populations in Individual 4: Solid and open circles indicate K103N positive and negative bulk sequence results, respectively. 2015 PloS one Figure HIV K103N;K103N 16;83 21;88 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. A solid triangle indicates K103N-positive amplicon at ID 9. 2015 PloS one Figure HIV K103N 27 32 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. A solid triangle indicates sequence data of K103N-positive amplicon derived from ID 2 sample. 2015 PloS one Figure HIV K103N 44 49 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Two solid triangles indicate T215I-positive AS-PCR amplicon from ID 17 and 21 samples. 2015 PloS one Figure HIV T215I 29 34 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. (A) katG S315T (isoniazid); gidB 130 bp deletion (streptomycin); 1957 (95% HPD: 1937-1971); (B) inhA promoter -8 (isoniazid and ethionamide); 1964 (95% HPD: 1948-1976); (C) embB M306V (ethambutol); 1967 (95% HPD: 1950-1978); (D) rpoB L452P (rifampicin); pncA 1bp insertion (pyrazinamide); 1984 (95% HPD: 1974-1992); and (E) rpoB D435G (rifampicin); rrs 1400 (kanamycin); gyrA A90V (ofloxacin); 1995 (95% HPD: 1988-1999). 2015 PLoS medicine Figure HIV A90V;D435G;L452P;M306V;S315T 376;329;234;178;9 380;334;239;183;14 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. (A) Proviral plasmids transiently expressing wild type or W252A RT mutant HIV-1 in HEK293T cells were visualized by western blot using a rabbit anit-HIV-1 antibody. 2015 PLoS pathogens Figure HIV W252A 58 63 RT 64 66 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. (B) Quantitative RT-PCR analysis of viral RNA in nevirapine-treated TZM-bl cells (to block reverse transcription of viral genomic RNA) infected with wild type or W252A RT HIV-1 or their heat-inactivated controls. 2015 PLoS pathogens Figure HIV W252A 162 167 RT;RT;RT 91;17;168 112;19;170 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. (C) Western blot of concentrated HIV-1 virus particles from culture supernatants expressing wild type or W252A RT HIV-1, detecting with anti-HIV-1 (left, human serum, NIH AIDS reagent) or anti-RT antibodies (right). 2015 PLoS pathogens Figure HIV W252A 105 110 RT;RT 111;193 113;195 AIDS 171 175 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. (D) The RT activities of wild type and W252A RT mutated viruses were measured using a standard RT colorimetric assay and normalized to CA levels in each sample. 2015 PLoS pathogens Figure HIV W252A 39 44 Capsid;RT;RT;RT 135;8;45;95 137;10;47;97 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. (E) Jurkat cells were infected with wild type or W252A RT mutant virus using equivalent amount of CA (500 ng CA/107 cells) or (F) equivalent amount of RT (5 ng of RT/107 cells). 2015 PLoS pathogens Figure HIV W252A 49 54 Capsid;Capsid;RT;RT;RT 98;109;55;151;163 100;111;57;153;165 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. A p value for the wild type and W252A RT mutant HIV-1 outcome is shown. 2015 PLoS pathogens Figure HIV W252A 32 37 RT 38 40 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. A W252A RT mutation inhibits HIV-1 reverse transcription and replication. 2015 PLoS pathogens Figure HIV W252A 2 7 RT;RT 35;8 56;10 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. A W252A RT mutation reduces the association of RT with eEF1A in cells. 2015 PLoS pathogens Figure HIV W252A 2 7 RT;RT 8;47 10;49 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Foci indicating association of RT with eEF1A were detected by fluorescence microscopy of cells infected with wild type or W252A RT mutant virus (bottom left panel), or with the same viruses that were heat-inactivated prior to infection. 2015 PLoS pathogens Figure HIV W252A 122 127 RT;RT 31;128 33;130 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. HIV-1 containing a W252A RT mutant has decreased ability to interact with eEF1A. 2015 PLoS pathogens Figure HIV W252A 19 24 RT 25 27 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. However, a W252A RT mutant HIV-1 is unaffected by Did B because its interaction with eEF1A, or with a eEF1A - Did B complex, is downregulated and catalyzes reverse transcription in either the presence or absence of Did B albeit at reduced efficiency. 2015 PLoS pathogens Figure HIV W252A 11 16 RT;RT 156;17 177;19 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Mutations flanking L295A and L303A, T296A and L301A, were included as controls. 2015 PLoS pathogens Figure HIV L295A;L301A;L303A;T296A 19;46;29;36 24;51;34;41 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Only the L303A RT mutation reduced interaction with eEF1A in a co-IP assay as performed in Fig 2. 2015 PLoS pathogens Figure HIV L303A 9 14 RT 15 17 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The cells were infected with VSV-G psuedotyped wild type (C and E) or W252A RT mutant (D and F) HIV-1. 2015 PLoS pathogens Figure HIV W252A 70 75 RT 76 78 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. Mutated residues V77I and L33F are shown in yellow. 2015 BMC bioinformatics Figure HIV L33F;V77I 26;17 30;21 26695135 Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease. Mutated residues V77I, L33F and K20T are shown in yellow. 2015 BMC bioinformatics Figure HIV K20T;L33F;V77I 32;23;17 36;27;21 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Major NNRTI-associated DRMs (HIVDB score >=60) included: L100I, K101P, K103N/S, V106A/M, Y181C/I/V, Y188L/H/C, G190A/S/E/Q, and M230L. 2015 PloS one Figure HIV G190A;G190E;G190Q;G190S;K101P;K103N;K103S;L100I;M230L;V106A;V106M;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 111;111;111;111;64;71;71;57;128;80;80;89;89;89;100;100;100 122;122;122;122;69;78;78;62;133;87;87;98;98;98;109;109;109 NNRTI 6 11 26717411 HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. Major NRTI-associated DRMs (HIVDB score >=30) included K65R, D67 deletion, T69 insertion, K70R, L74V/I, Y115F, Q151M, M184I/V, and T215F/Y. 2015 PloS one Figure HIV K65R;K70R;L74I;L74V;M184I;M184V;Q151M;T215F;T215Y;Y115F 55;90;96;96;118;118;111;131;131;104 59;94;102;102;125;125;116;138;138;109 NRTI 6 10 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. Analysis of clinical specimens and plasmid standards by paper capture, denaturation, and detection (CDD) and plate CDD for mutations K103N and Y181C. 2016 PloS one Figure HIV K103N;Y181C 133;143 138;148 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. Analysis of clinical specimens and plasmid standards by paper capture, denaturation, and detection (CDD) and plate CDD for mutations M184V and G190A. 2016 PloS one Figure HIV G190A;M184V 143;133 148;138 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. Comparison of paper Capture, Denaturation, and Detection (CDD) and plate CDD for analysis of a plasmid standard mixture series for mutation Y181C. 2016 PloS one Figure HIV Y181C 140 145 26751207 Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation. MUT and WT signals obtained by paper and plate CDD format OLA at codons K103N, Y181C, M184V and G190A from 26 clinical specimens were used to calculate MUT Ratios. 2016 PloS one Figure HIV G190A;K103N;M184V;Y181C 96;72;86;79 101;77;91;84 26850643 Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. Red boxes: TAMs; purple boxes: Q151M MDR pathway; cyan box: EFV resistance mutation; green box: K65R mutation; yellow boxes: all other mutations. 2016 Nucleic acids research Figure HIV K65R;Q151M 96;31 100;36 26870021 Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. The mutations V32I, I47V, and I50V, which appeared during the in vitro selection, are highlighted with red letters. 2016 Frontiers in microbiology Figure HIV I47V;I50V;V32I 20;30;14 24;34;18 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. (A) is the curve of the dose-response of 3 viruses (V179E\H221Y\T215Y, V179E\Y181C\T215Y and WT NL4.3) in d4T. 2016 PloS one Figure HIV H221Y;T215Y;T215Y;V179E;V179E;Y181C 58;64;83;52;71;77 63;69;88;58;76;82 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. (B) is the curve of the dose-response of 2 viruses (K103N\H221Y\Y181C\T215Y and WT NL4.3) in EFV. 2016 PloS one Figure HIV H221Y;K103N;T215Y;Y181C 58;52;70;64 63;58;75;69 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. (C) is the curve of the dose-response of 3 viruses (G48V\I54V\V82A, M46I\N88S and WT NL4.3) in IDV. 2016 PloS one Figure HIV G48V;I54V;M46I;N88S;V82A 52;57;68;73;62 57;61;72;77;66 26930645 The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope. (D) is the curve of the dose-response of 3 viruses (G48V\I54V, V82A and WT NL4.3) in SQV. 2016 PloS one Figure HIV G48V;I54V;V82A 52;57;63 57;61;67 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. (B) Renilla luciferase (hRluc) activity after transfection of the minigene expressing Nef(Y135), Nef(Y135F), Gag18-46 fused to hRluc or mock controls (culture without transfection). 2016 PloS one Figure HIV Y135F 101 106 Nef;Nef;Gag 86;97;109 89;100;112 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. (C) Recognition of endogenously expressed epitopes derived from Nef(Y135), Nef(Y135F) and Gag18-46 minigenes by dually specific CTL clones T26-102 or C1-28. 2016 PloS one Figure HIV Y135F 79 84 Nef;Nef;Gag 64;75;90 67;78;93 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. (D) Double-tetramer staining of CTL clone T26-102 with A*24:02/Nef134-8(Y135) tetramer-allophycocyanin (Tet-8(Y135)-APC) and A*24:02/Nef134-8(Y135F) tetramer-phycoerythrin (Tet-8(Y135F)-PE) (left) and CTL clone C1-28 with A*24:02/Nef134-10(Y135) tetramer-allophycocyanin (Tet-10(Y135)-APC) and A*24:02/Nef134-10(Y135F) tetramer-phycoerythrin (Tet-10(Y135F)-PE) (right). 2016 PloS one Figure HIV Y135F;Y135F;Y135F;Y135F 142;179;312;350 147;184;317;355 Nef;Nef;Nef;Nef 63;133;230;302 66;136;233;305 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Binding of Nef134-8 (blue circles) and Nef134-10 (red circles) and their Y135F-containing peptide variants (blue and red triangles, respectively) to T2 cells expressing A*24:02 was measured. 2016 PloS one Figure HIV Y135F 73 78 Nef;Nef 11;39 14;42 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Longitudinal comparison of clinical markers between HLA-A*24:02-positive patients inferred to have acquired the Y135F-containing virus and others. 2016 PloS one Figure HIV Y135F 112 117 26953793 Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. Plasma viral loads (copies/ml; A) and CD4 T cell counts (cells/mul; B) at the first visit and 50 week intervals afterwards are shown for patients for whom de novo infection with HIV-1 containing Y135 could not be ruled out and patients inferred to have acquired Y135F at transmission. 2016 PloS one Figure HIV Y135F 262 267 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. a Cryo-TEM image of conical A204C CA assemblies. 2016 Retrovirology Figure HIV A204C 28 33 Capsid 34 36 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. d Topographic AFM image of E45A conical CA assembly. 2016 Retrovirology Figure HIV E45A 27 31 Capsid 40 42 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. f Cross-sectional analysis of WT and E45A cores, black and red lines, respectively. 2016 Retrovirology Figure HIV E45A 37 41 27107820 HIV-1 capsid is involved in post-nuclear entry steps. a Jurkat cells were infected at an MOI of 0.5 with HIV-1GFP WT, A105S or N74D mutants in the presence or absence of 3 muM C-A1. 2016 Retrovirology Figure HIV A105S;N74D 64;73 69;77 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Average values +-SD of at least four independent experiments are shown for WT virus and three experiments for N74D or A105S viruses. 2016 Retrovirology Figure HIV A105S;N74D 118;110 123;114 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Cells were infected with HIV-1GFP WT, N74D or A105S mutants in the presence of 1 muM CsA alone or in combination with 3 muM C-A1. 2016 Retrovirology Figure HIV A105S;N74D 46;38 51;42 27107820 HIV-1 capsid is involved in post-nuclear entry steps. e Jurkat cells were infected with HIV-1GFP WT, A105S or N74D capsid mutants at an MOI of 0.1 in the presence of 3 muM C-A1 and the quantity of integrated viral DNA was measured by Alu-LTR TaqMan qPCR 1 week post-infection. 2016 Retrovirology Figure HIV A105S;N74D 47;56 52;60 Capsid;LTR 61;184 67;187 27107820 HIV-1 capsid is involved in post-nuclear entry steps. e These cells were used to perform CsA washout assays upon infection with HIV-1GFP WT or capsid mutant N74D. 2016 Retrovirology Figure HIV N74D 103 107 Capsid 89 95 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Each dot on the graph represents an independent experiment (note that five experiments were carried out with the A105S mutant virus). 2016 Retrovirology Figure HIV A105S 113 118 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Mutant viruses N74D and A105S proceed through a capsid-independent pathway and are insensitive to C-A1. 2016 Retrovirology Figure HIV A105S;N74D 24;15 29;19 Capsid 48 54 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. a K65R series, b L74V series, c K103N series, d E138K series, e M184I series, and f M184V series. 2016 Retrovirology Figure HIV E138K;K103N;K65R;L74V;M184I;M184V 48;32;2;17;64;84 53;37;6;21;69;89 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Asterisk and dollar sign indicate statistically significant difference from single RT mutants alone and from the R263K-containing viruses, respectively (Student's t test, P < 0.05) 2016 Retrovirology Figure HIV R263K 113 118 RT 83 85 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Asterisk and dollar sign indicate statistically significant difference from single RT mutants alone and from the R263K-containing viruses, respectively (Student's t test, P < 0.05). 2016 Retrovirology Figure HIV R263K 113 118 RT 83 85 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. b L74V series including NL4.3L74V, NL4.3R263K-L74V, and NL4.3H51Y/R263K-L74V. 2016 Retrovirology Figure HIV L74V;L74V;L74V;L74V;R263K 29;2;46;72;66 33;6;50;76;71 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Best-fit curves and data for EC50 values, 95 % confidence intervals and fold changes (FC) relative to single RT mutations alone are showed in the insets: a K65R series including NL4.3K65R, NL4.3R263K-K65R, and NL4.3H51Y/R263K-K65R. 2016 Retrovirology Figure HIV K65R;K65R;K65R;K65R;R263K 183;156;200;226;220 187;160;204;230;225 RT 109 111 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. c K103N series including NL4.3K103N, NL4.3R263K-K103N, and NL4.3H51Y/R263K-K103N. 2016 Retrovirology Figure HIV K103N;R263K;K103N;K103N;K103N;R263K 30;42;2;48;75;69 35;47;7;53;80;74 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. d E138K series including NL4.3E138K, NL4.3R263K-E138K, and NL4.3H51Y/R263K-E138K. 2016 Retrovirology Figure HIV E138K;R263K;E138K;E138K;E138K;R263K 30;42;2;48;75;69 35;47;7;53;80;74 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. e M184I series including NL4.3M184I, NL4.3R263K-M184I, and NL4.3H51Y/R263K-M184I. 2016 Retrovirology Figure HIV M184I;R263K;M184I;M184I;M184I;R263K 30;42;0;48;75;69 35;47;7;53;80;74 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Effects of R263K and H51Y/R263K in combination with different RTI substitutions on viral infectivity in TZM-bl reporter cells. 2016 Retrovirology Figure HIV H51Y;R263K;R263K 21;11;26 25;16;31 RT 62 65 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. f M184V series including NL4.3M184V, NL4.3R263K-M184V, and NL4.3H51Y/R263K-M184V. 2016 Retrovirology Figure HIV H51Y;M184V;R263K;M184V;M184V;M184V;R263K 64;30;42;0;48;75;69 68;35;47;7;53;80;74 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. WT, R263K and H51Y/R263K viruses are also presented in each data series from a to f. 2016 Retrovirology Figure HIV H51Y;R263K;R263K 14;4;19 18;9;24 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Striped bars represent sequences with TDF-associated mutation K65R. 2016 Journal of the International AIDS Society Figure HIV K65R 62 66 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. (A) THP-1 cells were pretreated with increasing doses of IFN-alpha and infected 24 h later with an equal amount of VSV-G-pseudotyped wild-type HIV-1 GFP lentiviral vector DeltaR8.91 or CA mutant N74D or P90A, as measured by SG-PERT and 293T titration. 2016 Journal of virology Figure HIV N74D;P90A 195;203 199;207 Capsid 185 187 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. (B) In parallel, cells were infected 24 h after IFN-alpha treatment with a serial dilution of VSV-G pseudotyped wild-type NL4.3GFP or the CA mutants N74D or A105T. 2016 Journal of virology Figure HIV A105T;N74D 157;149 162;153 Capsid 138 140 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. (C) Wild-type THP-1 and the MX2 knockout cell clones (g1-1 and g2-4) were treated for 24 h with 500 U/ml IFN-alpha and then infected with a serial dilution of VSV-G-pseudotyped NL4.3GFP wild-type, CA N74D or CA P90A or CA A105T mutant viruses. 2016 Journal of virology Figure HIV A105T;N74D;P90A 222;200;211 227;204;215 Capsid;Capsid;Capsid 197;208;219 199;210;221 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. (D) THP-1 cells were treated for 24 h with 500 U/ml IFN-alpha and then infected with a serial dilution of VSV-G-pseudotyped wild-type or CA P90A mutant HIV-1 GFP LV in the presence or absence of 2.5 muM Cs or DMSO as a carrier control. 2016 Journal of virology Figure HIV P90A 140 144 Capsid 137 139 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. (F) Parental THP-1 cells, Cntrl cells, or CypA CRISPR/Cas9 cell clones were treated with a serial dilution of IFN-alpha for 24 h and then infected with VSV-G-pseudotyped wild-type or CA P90A mutant NL4.3GFP at similar doses. 2016 Journal of virology Figure HIV P90A 186 190 Capsid;Capsid 54;183 56;185 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. For data derived from IFN-alpha-treated samples, a paired two-tailed t test with confidence interval of 0.95 was performed (HIV-1 NL4.3GFP wild type: Cntrl versus CypAg1-1 [**, P = 0.0047]; Cntrl versus CypAg1-2 [**, P = 0.0058]; Cntrl versus CypAg1-3 [***, P = 0.0002]; NL4.3GFP P90A: Cntrl versus CypAg1-1 [n.s.]; Cntrl versus CypAg1-2 [n.s.]; Cntrl versus CypAg1-3 [n.s.]; Cntrl cells: NL4.3GFP wild type versus NL4.3GFP P90A [***, P < 0.0001]). 2016 Journal of virology Figure HIV P90A;P90A 280;424 284;428 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. For IFN-alpha-treated samples, a paired two-tailed t test with CI = 0.95 was performed (wild type [WT] versus P90A, P <= 0.0001; WT versus N74D, P <= 0.0001). 2016 Journal of virology Figure HIV N74D;P90A 139;110 143;114 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. HIV-1 CA mutants N74D and P90A have increased sensitivity to IFN-alpha-induced suppression in diverse cell types. 2016 Journal of virology Figure HIV N74D;P90A 17;26 21;30 Capsid 6 8 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Hypersensitivity of the HIV-1 CA mutant N74D to IFN-alpha occurs at the stages of reverse transcription and nuclear import. 2016 Journal of virology Figure HIV N74D 40 44 RT;Capsid 82;30 103;32 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Parental THP-1 or MX2g2-4 CRISPR/Cas9 cells were infected with VSV-G-pseudotyped NL4.3GFP wild-type or N74D CA mutant virus. 2016 Journal of virology Figure HIV N74D 103 107 Capsid;Capsid 33;108 35;110 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Statistical analyses were analogous to panel A (IFN-alpha-treated samples: WT versus P90A [P <= 0.0001] and WT versus N74D [P <= 0.0001]). 2016 Journal of virology Figure HIV N74D;P90A 118;85 122;89 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Statistical evaluation was performed as in panel A (IFN-alpha-treated samples: WT versus P90A [P = 0.0012] and WT versus N74D [P = 0.0002]). 2016 Journal of virology Figure HIV N74D;P90A 121;89 125;93 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. The statistical tests were performed as in panel A (IFN-alpha-treated samples: WT versus P90A [P <= 0.0001] and WT versus N74D [P <= 0.0001]). 2016 Journal of virology Figure HIV N74D;P90A 122;89 126;93 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Without IFN-alpha treatment, no significant differences between Cntrl cells and CypAg1-1, CypAg1-2, or CypAg1-3 were detected for both NL4.3GFP wild type and NL4.3GFP P90A. 2016 Journal of virology Figure HIV P90A 167 171 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. (A,B) Monocyte derived macrophages (MDM) and HeLa cells were synchronously infected with VSVg pseudotyped HIV-1 reporter virus (MOI 0.3 for MDM and MOI 0.6 for HeLa cells) bearing either the wildtype (WT) CA or N74D and P90A CA mutants. 2016 PLoS pathogens Figure HIV N74D;P90A;N74D;P90A 212;221;211;220 216;225;215;224 Capsid;Capsid 205;225 207;227 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. (A) MDM or HeLa cells were synchronously infected HIV-1 GFP pseudotyped with VSV-g bearing either the wildtype (WT) CA or N74D and P90A CA mutants(MDMs MOI 0.3, HeLa MOI 0.6).Cells fixed at 3h post infection, incubated with primary antibodies to Nup358 and HIV-1 CA, followed by secondary antibodies specific for these antibodies conjugated to the PLUS and MINUS PLA oligonucleotides. 2016 PLoS pathogens Figure HIV N74D;P90A;N74D;P90A 123;132;122;131 127;136;126;135 Capsid;Capsid;Capsid 116;136;263 118;138;265 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. (A)MDMs were synchronously infected with HIV-1 GFP pseudotyped with VSV-g bearing either the wildtype (WT) CA or N74D and P90A CA mutants (MOI 0.3).Cells fixed 1 and 3h post infection and stained for viral capsid protein p24 (red) and Nup358 (green). 2016 PLoS pathogens Figure HIV N74D;P90A;N74D;P90A 114;123;113;122 118;127;117;126 Capsid;p24;Capsid;Capsid 206;221;107;127 212;224;109;129 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. HeLa cells treated with scrambled, Nup358 or KIF5B siRNA for 72h were subjected to synchronized infected with 100ng of VSVg pseudotyped HIV-1 reporter virus bearing either the wildtype (WT) CA or N74D and P90A CA mutants. 2016 PLoS pathogens Figure HIV N74D;P90A 196;205 200;209 Capsid;Capsid 190;210 192;212 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. (A) 3'-Processing of the canonical 21 bp substrate by the WT, Q146A, Q146E, Q146T and Q146K IN mutants. 2016 Nucleic acids research Figure HIV Q146A;Q146E;Q146K;Q146T 62;69;86;76 67;74;91;81 IN 92 94 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. (B) ST activity of the WT, Q146A, Q146E, Q146T and Q146K IN mutants with the precleaved 19/21 bp substrate. 2016 Nucleic acids research Figure HIV Q146A;Q146E;Q146K;Q146T 27;34;51;41 32;39;56;46 IN 57 59 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. 3'-Processing and strand transfer (ST) activity of the HIV IN WT and Q146A, Q146E, Q146T and Q146K mutants. 2016 Nucleic acids research Figure HIV Q146A;Q146E;Q146K;Q146T 69;76;93;83 74;81;98;88 IN 59 61 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Differential 3'-processing of modified DNA substrates by the wild-type IN (WT) and the drug-resistant IN mutant G140S-Q148H (SH), and inhibition of 3-processing by raltegravir (RAL) and dolutegravir (DTG). 2016 Nucleic acids research Figure HIV G140S;Q148H 112;118 117;123 IN;IN 71;102 73;104 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Modeling of the WT and G140S-Q148H (SH) IN active sites in complexes with the modified substrates. 2016 Nucleic acids research Figure HIV G140S;Q148H 23;29 28;34 IN 40 42 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. a Western blot analysis of the WT (left) and F56C (right) fusion precursors. 2016 Retrovirology Figure HIV F56C 45 49 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. a-c Electron microscopy of particles associated with cells transfected with pEnv and pNL4-3DeltaEnv-WT (a), -S40A (b), or -S40F (c). 2016 Retrovirology Figure HIV S40A;S40F 109;123 113;127 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Impact of Gagp6 S40A/Pol p6*-PR F56C mutation on IDV susceptibility. 2016 Retrovirology Figure HIV F56C 32 36 Pol;Gag;Gag;PR 21;10;25;29 24;13;27;31 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. p6 S40A is Gag S488A (HXB2 numbering) 2016 Retrovirology Figure HIV S488A 15 20 Gag;Gag 11;0 14;2 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. p6 S40A is Gag S488A (HXB2 numbering). 2016 Retrovirology Figure HIV S488A 15 20 Gag;Gag 11;0 14;2 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The F56C mutation reduces mature PR release from a model precursor. 2016 Retrovirology Figure HIV F56C 4 8 PR 33 35 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. c Modelling of the rare L188F mutation, shown to reduce viral replication capacity. 2016 Retrovirology Figure HIV L188F 24 29 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. d Frequency of the Gag variant L188F present in all three family members in chronically infected adults with C clade infection (data from Ref.) 2016 Retrovirology Figure HIV L188F 31 36 Gag 19 22 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. d Frequency of the Gag variant L188F present in all three family members in chronically infected adults with C clade infection (data from Ref.). 2016 Retrovirology Figure HIV L188F 31 36 Gag 19 22 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. e Modelling of the T186S mutation (black arrow), shown to be detrimental to viral health. 2016 Retrovirology Figure HIV T186S 19 24 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. f Structural modeling of the T190I mutation (black arrow) that can rescue the T186S mutation, restoring viral replication capacity. 2016 Retrovirology Figure HIV T186S;T190I 78;29 83;34 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Primary INSTI resistance mutations are T66I/A/K, E92Q/G, T97A, Y143C/H/R, S147G, Q148H/K/R, and N155H, and other INSTI resistance mutations are H51Y, L68I/V, V72A/N/T, L74M, Q95K/R, F121C/Y, A128T, E138A/K, G140A/C/S, P145S, Q146I/K/L/P/R, V151L/A, S153A/F/Y, E157K/Q, G163K/R, E170A, and R263K in IN. 2016 Antimicrobial agents and chemotherapy Figure HIV A128T;E138A;E138K;E157K;E157Q;E170A;E92G;E92Q;F121C;F121Y;G140A;G140C;G140S;G163K;G163R;H51Y;L68I;L68V;L74M;N155H;P145S;Q146I;Q146K;Q146L;Q146P;Q146R;Q148H;Q148K;Q148R;Q95K;Q95R;R263K;S147G;S153A;S153F;S153Y;T66A;T66I;T66K;T97A;V151A;V151L;V72A;V72N;V72T;Y143C;Y143H;Y143R 191;198;198;260;260;278;49;49;182;182;207;207;207;269;269;144;150;150;168;96;218;225;225;225;225;225;81;81;81;174;174;289;74;249;249;249;39;39;39;57;240;240;158;158;158;63;63;63 196;205;205;267;267;283;55;55;189;189;216;216;216;276;276;148;156;156;172;101;223;238;238;238;238;238;90;90;90;180;180;294;79;258;258;258;47;47;47;61;247;247;166;166;166;72;72;72 INSTI;INSTI;IN 8;113;298 13;118;300 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. (A) HeLa cells were co-transfected with 0.8 mug of pCAGGS/Gag and 1.5 mug of pCAGGS/eCFP-TSG101 either without/with 0.5 mug of pCAGGS/HA-Vpr or pCAGGS/HA-Vpr A30F for 48 h prior to immunofluorescence staining with an anti-Gag and anti-HA antibodies, followed by an Alexa Fluor 594 goat anti-rabbit antibody and an Alexa Fluor 633 goat anti-mouse antibody. 2016 PloS one Figure HIV A30F 158 162 Vpr;Vpr;Gag;Gag 137;154;58;222 140;157;61;225 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. (C) HEK293T cells were transfected with 0.8 mug of pCAGGS/Gag, or with 0.8 mug of pCAGGS/Gag plus 1.5 mug of pCAGGS/FLAG-TSG101 either without/with different amounts of pCAGGS/Vpr A30F or 0.08 mug of pCAGGS/Vpr (positive control). 2016 PloS one Figure HIV A30F 180 184 Vpr;Vpr;Gag;Gag 176;207;58;89 179;210;61;92 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. a The infectivity levels of ENF-resistant mutants, V38A, N43D, and Q40H, and of C34-resistant mutants, I37K, N126K, L204I, I37K/N126K, I37K/L204I, N126K/L204I, and C34r, are shown. 2016 Retrovirology Figure HIV I37K;I37K;I37K;L204I;L204I;L204I;N126K;N126K;N126K;N43D;Q40H;V38A 103;123;135;116;140;153;109;128;147;57;67;51 107;127;139;121;145;158;114;133;152;61;71;55 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. b Structures of the extracellular portion of the HIV-1 JR-FL gp41 trimer with and without a I37K mutation. 2016 Retrovirology Figure HIV I37K 92 96 gp41 61 65 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Molecular modeling and MD simulation of the extracellular portion of the HIV-1 JR-FL gp41 trimer with and without a I37K mutation were performed using modules in the Molecular Operating Environment and the AMBER 11 program package. 2016 Retrovirology Figure HIV I37K 116 120 gp41 85 89 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The effects of N126K, N126K/L204I, C34r, and I37K mutations on fusion kinetics were determined by dual split protein (DSP)-dependent cell-cell fusion assays. 2016 Retrovirology Figure HIV I37K;L204I;N126K;N126K 45;28;15;22 49;33;20;27 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Three mutations that together confer C34 resistance, I37K, N126K, and L204I, were examined for their effect on the neutralization sensitivity to anti-CD4bs MAbs, VRC01, 49G2, and 42F9, (a) and to sCD4 (b) using single (left) and double (right) mutants. 2016 Retrovirology Figure HIV I37K;L204I;N126K 53;70;59 57;75;64 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Three mutations that together confer C34 resistance, I37K, N126K, and L204I, were examined for their effect on the neutralization sensitivity to the anti-V3 MAbs, KD247, 16G6, and 0.5gamma, (a) and to the anti-MPER MAb 10E8 (b) using single (left) and double (right) mutants. 2016 Retrovirology Figure HIV I37K;L204I;N126K 53;70;59 57;75;64 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. NNRTI PDR mutation frequency trends; only surveillance drug resistance mutations to NNRTI with frequency over 0.5% and E138A are included. 2016 PloS one Figure HIV E138A 119 124 NNRTI;NNRTI 0;84 5;89 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. MLV and HIV-1 bearing capsid G89V mutation are insensitive to restriction by TRIM11 on the early stage of replication. 2016 Retrovirology Figure HIV G89V 29 33 Capsid 22 28 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. (E) Summary of the results of experiments with lentiviral vectors harboring combination mutant Nef proteins of C.BR92025 (CR13W V84A) and B.JRFL (BW13R A84V K92E) from panels A and C, respectively. 2016 mSphere Figure HIV A84V;K92E;V84A 152;157;128 156;161;132 Nef 95 98 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. Zoomed-in images showing A84 (top right) and mutant A84V (bottom right) are also shown. 2016 mSphere Figure HIV A84V 52 56 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. Zoomed-in images showing W13 (top right) and mutant W13R (bottom right) are also shown. 2016 mSphere Figure HIV W13R 52 56 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. a FACS-based cell surface staining assay of JRFL, JRCSF and the mutants C2, N197D, N230D, N289K (all in JRCSF) with 2G12 and b12 over a range of antibody concentrations. 2016 Retrovirology Figure HIV N197D;N230D;N289K 76;83;90 81;88;95 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. b FACS-based cell surface assay of JRFL, JRCSF and the mutant JRCSF (N197D) with VRC01 over a range of antibody concentrations. 2016 Retrovirology Figure HIV N197D 69 74 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. c Western blot analysis of VRC01 immunoprecipitates of plasma membrane fraction of JRFL and JRCSF(N197D) transfected 293T cell lysates with anti-clade B Env rabbit Abs. 2016 Retrovirology Figure HIV N197D 98 103 Env 153 156 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Comparative binding of JRFL, JRCSF and JRFL (E168K) to V2 "cap" targeted glycan and conformation-dependent Abs PG9 and PGT145 over a range of antibody concentrations by FACS-based cell surface staining assay. 2016 Retrovirology Figure HIV E168K 45 50 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. d Western blot analysis of VRC01 immunoprecipitate of plasma membrane fraction of JRCSF(N197D) transfected 293T cell lysates and crude lysate of YU2 with anti-clade B Env rabbit Abs. 2016 Retrovirology Figure HIV N197D 88 93 Env 167 170 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. FACS-based cell surface staining assay of JRFL, JRCSF and JRCSF (N197D) with glycan and quaternary epitope-dependent bNAbs PG9 and PGT128 and CD4i Abs 17b and 412d over a range of antibody concentrations. 2016 Retrovirology Figure HIV N197D 65 70 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. N197D mutant of JRCSF retains native conformation. 2016 Retrovirology Figure HIV N197D 0 5 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. N197D mutation in JRCSF restores CD4-bs-directed bNAb binding to JRCSF. 2016 Retrovirology Figure HIV N197D 0 5 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. (D) CLEANEX-PM data for L85A at pH 7. 2016 PloS one Figure HIV L85A 24 28 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. (D) The amide proton exchange was monitored by CLEANEX-PM at pH 7 and 25 C for E12A. 2016 PloS one Figure HIV E12A 79 83 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Effects of the L85A mutation on the chemical shifts of p17. 2016 PloS one Figure HIV L85A 15 19 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. R2/R1 values (A) and order parameter S2 (B) based on relaxation studies of E12A at pH 5.5. 2016 PloS one Figure HIV E12A 75 79 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. R2/R1 values (A) and order parameter S2 values (B) based on the relaxation studies of E12A at pH 7. 2016 PloS one Figure HIV E12A 86 90 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Relaxation data for E12A at pH 5.5 including (A) T2, (B) T1, and (C) heteronuclear NOE. 2016 PloS one Figure HIV E12A 20 24 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Relaxation studies on (A) T2 and (B) T1, and (C) heteronuclear NOE of E12A. 2016 PloS one Figure HIV E12A 70 74 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Superimposed HSQC spectra of p17 E12A (A: red) and L85A (B: blue) with WT (black) at pH 7 and 25 C. 2016 PloS one Figure HIV L85A 51 55 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The chemical shift differences of (A) CA, (B) CB, and (C) CO between L85A and WT at pH 7 are indicated. 2016 PloS one Figure HIV L85A 69 73 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The differences in the chemical shifts between E12A and WT at pH 7. 2016 PloS one Figure HIV E12A 47 51 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The values of chemical shifts are indicated for L85A and WT (S2 and S3 Tables). 2016 PloS one Figure HIV L85A 48 52 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The values of chemical shifts are shown for E12A (S1 Table). 2016 PloS one Figure HIV E12A 44 48 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Conformational Changes in Hinge Loop Mutations E35D, M36I and S37N. 2016 PloS one Figure HIV E35D;M36I;S37N 47;53;62 51;57;66 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Conformational Changes induced by Flap Mutation Cluster of M46L, G48V and I54V. 2016 PloS one Figure HIV G48V;I54V;M46L 65;74;59 69;78;63 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Distal mutations A71V and I93L in PRS17 are associated with shift in 70's beta strand by ~1 A and loss of the ion pair between His69 and the carboxylate tail of the second subunit. 2016 PloS one Figure HIV A71V;I93L 17;26 21;30 PR 34 36 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Effects of Distal mutations A71V, L90M and I93L. 2016 PloS one Figure HIV A71V;I93L;L90M 28;43;34 32;47;38 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Flap mutation cluster of M46L, G48V and I54V in PRS17/DRV compared to PR/DRV. 2016 PloS one Figure HIV G48V;I54V;M46L 31;40;25 35;44;29 PR;PR 48;70 50;72 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. I93L mutation in PRS17 results in loss of van der Waals contact observed between Ile93 and Leu 90 of wild-type PR. 2016 PloS one Figure HIV I93L 0 4 PR;PR 17;111 19;113 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. L10I mutation in PRS17 does not break the inter-monomer ion pair between Arg8 and Asp29' unlike L10F in PR20. 2016 PloS one Figure HIV L10F;L10I 96;0 100;4 Asp;PR;PR 82;17;104 85;19;106 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. L90M mutation in PRS17 (green) induces shortened C-H...O interaction between Met90 and catalytic Asp25 in comparison to wild-type PR (gray). 2016 PloS one Figure HIV L90M 0 4 Asp;PR;PR 97;17;130 100;19;132 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Mutations introduced in WT PR to restrict autoproteolysis (Q7K, L33I and L63I) and avoid cysteine-thiol oxidation (C67A and C95A) are indicted by asterisks. 2016 PloS one Figure HIV C67A;C95A;L33I;L63I;Q7K 115;124;64;73;59 120;128;68;77;62 PR 27 29 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Note that K20R interacts with residues in the hinge loop although it is not contiguous in sequence with this region as described later. 2016 PloS one Figure HIV K20R 10 14 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. Two Alternate Conformations of Darunavir and the Active Site Mutation V82S in PRS17/DRV Dimer. 2016 PloS one Figure HIV V82S 70 74 PR 78 80 27992544 Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics. V82S mutation, proximal to the active site, is shown as a green sphere in each subunit. 2016 PloS one Figure HIV V82S 0 4 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (A, B) Fusion inhibition on efficacy switch mutation L203F (black circles) shown as percentage of own baseline, both n = 9. 2016 Pharmacology research & perspectives Figure HIV L203F 53 58 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (C, D) ELISA for efficacy switch mutation L203F (black circles) shown as percentage of WT baseline, both n = 3. 2016 Pharmacology research & perspectives Figure HIV L203F 42 47 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (E) ELISA for inactive mutation W248A with Maraviroc (white hexagons) and Aplaviroc (black hexagons) shown as percentage of WT baseline, both n = 3. 2016 Pharmacology research & perspectives Figure HIV W248A 32 37 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (F-H) Fluorescence microscopy of efficacy switch mutation L203F without ligand, with 10 mumol/L Maraviroc, and with 10 mumol/L Aplaviroc, representative experiment. 2016 Pharmacology research & perspectives Figure HIV L203F 58 63 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (I) ELISA for inactive mutation Y244A with Maraviroc (white diamonds) and Aplaviroc (black diamonds) shown as percentage of WT baseline, both n = 3. 2016 Pharmacology research & perspectives Figure HIV Y244A 32 37 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (J-L) Fluorescence microscopy on Y244A without ligand, with 10 mumol/L Maraviroc, and with 10 mumol/L Aplaviroc, representative cells. 2016 Pharmacology research & perspectives Figure HIV Y244A 33 38 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (M) ELISA for anchor point mutation Y251A with Maraviroc (white triangles) and Aplaviroc (black triangles) shown as percentage of WT baseline, both n = 3. 2016 Pharmacology research & perspectives Figure HIV Y251A 36 41 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (N-P) Fluorescence microscopy of Y251A without ligand, with 10 mumol/L Maraviroc, and with 10 mumol/L Aplaviroc, representative experiment. 2016 Pharmacology research & perspectives Figure HIV Y251A 33 38 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (Q) ELISA for anchor point mutation Y251A with Maraviroc (white circles) and Aplaviroc (black circles) shown as percentage of WT baseline, both n = 3. 2016 Pharmacology research & perspectives Figure HIV Y251A 36 41 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. (R-T) Fluorescence microscopy on E283A without ligand, with 10 mumol/L Maraviroc, and with 10 mumol/L Aplaviroc, representative experiment. 2016 Pharmacology research & perspectives Figure HIV E283A 33 38 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Fluorescence microscopy of W248A without ligand, with 10 mumol/L Maraviroc, and with 10 mumol/L Aplaviroc, representative cells. 2016 Pharmacology research & perspectives Figure HIV W248A 27 32 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Fusion inhibition on E283A (black circles) of (A) Maraviroc (n = 7) and (B) Aplaviroc (n = 6). 2016 Pharmacology research & perspectives Figure HIV E283A 21 26 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Fusion inhibition on W248A (black hexagons) of (C) Maraviroc (n = 8) and (D) Aplaviroc (n = 8). 2016 Pharmacology research & perspectives Figure HIV W248A 21 26 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Fusion inhibition on Y244A (black diamonds) of (A) Maraviroc (n = 9) and (B) Aplaviroc (n = 9). 2016 Pharmacology research & perspectives Figure HIV Y244A 21 26 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Fusion inhibition on Y251A (black triangles) of (C) Maraviroc (n = 8) and (D) Aplaviroc (n = 9). 2016 Pharmacology research & perspectives Figure HIV Y251A 21 26 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. *, T97A may require additional integrase mutations for reduced phenotypic susceptibility to EVG and/or RAL. 2017 PloS one Figure HIV T97A 3 7 IN 31 40 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Correlation of EVG and RAL susceptibility among patient-derived viruses containing T97A alone (pre-existing and emergent). 2017 PloS one Figure HIV T97A 83 87 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Fifty-five patient-derived viruses harboring T97A (or T97T/A) alone (i.e., in the absence of primary INSTI RAMs) were tested for phenotypic susceptibility to INSTIs, with data available for 45 isolates (pre-existing T97A: 38 of 47; emergent T97A alone: 7 of 8). 2017 PloS one Figure HIV T97A;T97A;T97A;T97A;T97T 45;54;216;241;54 49;60;220;245;60 INSTI;INSTI 101;158 106;164 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Fold change EC50 values against EVG (left panel) or RAL (right panel) were compared between and among overall pre-existing and emergent T97A alone populations by B versus non-B subtype (A), by TN versus TE (B), and by full T97A versus wild-type mixed T97T/A mutation (C). 2017 PloS one Figure HIV T97A;T97A;T97A;T97T 136;223;251;251 140;227;257;257 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Fold change EC50 values against EVG (left panel) or RAL (right panel) were compared between overall pre-existing and emergent T97A alone populations (A) and between pre-existing and emergent T97A alone populations with reduced susceptibility greater than or equal to biological cutoff (BCO) thresholds (B). 2017 PloS one Figure HIV T97A;T97A 126;191 130;195 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Left panel: Forty-seven patients had pre-existing T97A, of which 18 patients (TE = 3; TN = 15) enrolled on an INSTI-based regimen: 16 patients (1 TE [on EVG/r+TDF+DRV] and 15 TN [on EVG/COBI/FTC/TDF]) achieved HIV-1 RNA <50 copies/mL by study endpoint and were considered VS, 1 patient (1 TE [on EVG/r+TDF+DRV]) did not achieve HIV-1 RNA <50 copies/mL by a non-protocol-defined virologic failure visit (Week 8) and was excluded from treatment outcome and study-specific resistance analysis (see Methods), and 1 patient (1 TE [on EVG/r+TDF+DRV]) maintained T97A and EVG sensitivity at confirmed virologic rebound (Week 40) without further development of antiretroviral resistance. 2017 PloS one Figure HIV T97A;T97A 50;556 54;560 INSTI 110 115 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Left panel: Forty-seven patients had pre-existing T97A: 16 patients (9 enrolled on INSTI: 1 TE [on EVG+TDF+DRV/r] and 8 TN [on EVG/COBI/FTC/TDF]) with reduced EVG susceptibility, 22 patients (9 enrolled on INSTI: 2 TE [on EVG/r+TDF+DRV] and 7 TN [on EVG/COBI/FTC/TDF]) with EVG sensitivity, and 9 patients with no phenotypic data. 2017 PloS one Figure HIV T97A 50 54 INSTI;INSTI 83;206 88;211 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Open circles represent emergent T97A alone isolates (i.e., in the absence of primary INSTI RAMs) at first protocol-defined virologic failure visits with INSTI resistance (7 of 8 with data); blue and red indicate EVG and RAL-based regimens, respectively. 2017 PloS one Figure HIV T97A 32 36 INSTI;INSTI 85;153 90;158 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Overall fold change differences in EVG and RAL susceptibility between pre-existing and emergent T97A alone populations. 2017 PloS one Figure HIV T97A 96 100 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Pre- and on-treatment incidence of HIV-1 infected patients with T97A-based genotypic EVG resistance and impact on treatment outcome. 2017 PloS one Figure HIV T97A 64 68 HIV infections 35 49 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Pre- and on-treatment incidence of HIV-1 infected patients with T97A-based phenotypic EVG resistance. 2017 PloS one Figure HIV T97A 64 68 HIV infections 35 49 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Right panel: Eight patients (TE = 7; TN = 1) had emergent T97A alone (i.e., in the absence of primary INSTI RAMs): 4 patients (4 TE [2 on RAL+ABC+LPV/r, 1 on EVG/r+MVC+DRV, and 1 on EVG/r+TDF+DRV]) with reduced EVG susceptibility, 3 patients (3 TE [1 on EVG/r+TDF+DRV, 1 on EVG/r+FTC/TDF+LPV, and 1 on EVG/r+ETR+LPV]) with EVG sensitivity including 1 patient (1 TE [on EVG/r+ETR+LPV]) that withdrew consent and discontinued study drug at Week 144 and was excluded from treatment outcome and study-specific resistance analysis (see Methods), and 1 patient (1 TN [on EVG/COBI/FTC/TDF]) with no phenotypic data. 2017 PloS one Figure HIV T97A 58 62 INSTI 102 107 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Right panel: Eight patients (TE = 7; TN = 1) had emergent T97A alone (ie, in the absence of primary INSTI RAMs): 4 patients at first protocol-defined virologic failure (3 TE [1 on RAL+ABC+LPV/r, 1 on EVG/r+FTC/TDF+LPV, and 1 on EVG/r+MVC+DRV]; 1 TN [on EVG/COBI/FTC/TDF]), 2 patients at second protocol-defined virologic failure (2 TE [1 on EVG/r+TDF+DRV and 1 on RAL+ABC+LPV/r]), 1 patient at fourth protocol-defined virologic failure (1 TE [on EVG/r+TDF+DRV]), and 1 patient (1 TE [on EVG/r+ETR+LPV]) withdrew consent and discontinued study drug at Week 144 and was excluded from treatment outcome and study-specific resistance analysis (see Methods). 2017 PloS one Figure HIV T97A 58 62 INSTI 100 105 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Solid black circles represent pre-existing T97A isolates at pre-treatment visits (38 of 47 with data). 2017 PloS one Figure HIV T97A 43 47 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Stratified fold change differences in EVG and RAL susceptibility between and among pre-existing and emergent T97A alone populations. 2017 PloS one Figure HIV T97A 109 113 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The proportion of patients with reduced EVG susceptibility was low and similar between pre- and on-treatment T97A populations (P = 0.682). 2017 PloS one Figure HIV T97A 109 113 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Four clusters with K103N sequences are indicated and shown in more detail. 2017 Clinical infectious diseases Figure HIV K103N 19 24 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Percentage of newly diagnosed individuals entering into care in the Oduber Hospital in Aruba who received a resistance test at baseline (1A) and the percentage of tested individuals in whom transmission of a K103N variant was detected (1B) from 2010 until 2015. 2017 Clinical infectious diseases Figure HIV K103N 208 213 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Sequence names include reported route of transmission, the country of origin, the reported country of infection and presence of K103N. 2017 Clinical infectious diseases Figure HIV K103N 128 133 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. For the 6/5AL aptamer, Kd values under the conditions of these assays were 81 nM for subtype B RT and 57 nM for the R277K point mutant. 2017 Nucleic acids research Figure HIV R277K 116 121 RT 95 97 28334941 RNA-protein interactions govern antiviral specificity and encapsidation of broad spectrum anti-HIV reverse transcriptase aptamers. The 6/5AL aptamer (A), F1Pk (B) and arbitrary aptamer (C) were 5'-end labeled with 32P-ATP and added to aptamer-RT binding reactions containing various concentrations of subtype B RT or the R277K point mutant in binding buffer. 2017 Nucleic acids research Figure HIV R277K 190 195 RT;RT 112;180 114;182 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Likelihood of K65R mutation in subtype C viruses versus all other subtypes by current NRTI exposure. 2017 The Journal of antimicrobial chemotherapy Figure HIV K65R 14 18 NRTI 86 90 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Proportion of patients ever detected with K65R by exposure to selected NRTIs. 2017 The Journal of antimicrobial chemotherapy Figure HIV K65R 42 46 NRTI 71 76 28468838 HIV-1 Tat potently stabilises Mdm2 and enhances viral replication. S166A mutation abrogates Mdm2-mediated increase in HIV-1 replication by decreasing Mdm2 stability and its interaction with Tat. 2017 The Biochemical journal Figure HIV S166A 0 5 Tat 123 126 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Cluster 14947 (a and i) was selected with both dolutegravir and dolutegravir + lamivudine to ascertain the sequential appearance of R263K and M184V. 2017 The Journal of antimicrobial chemotherapy Figure HIV M184V;R263K 142;132 147;137 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Regarding lamivudine, one large cluster virus passaged with lamivudine acquired M184V leading to earlier viral escape by week 16; the remaining three large clusters developed M184I. 2017 The Journal of antimicrobial chemotherapy Figure HIV M184I;M184V 175;80 180;85 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. (B) Representative data of Tat variants[TatN12 (lack Ser46Phe) with Leu35Pro and Gly44Ser, TatVT6 (lack Ser46Phe) with B/C recombination and TatD60 (with Ser46Phe)] were aligned with wild-type Tat C. 2017 Frontiers in microbiology Figure HIV G44S;L35P;S46F;S46F;S46F 81;68;53;104;154 89;76;61;112;162 Tat;Tat;Tat;Tat 27;40;141;193 30;43;144;196 28640909 HIV-Tat regulates macrophage gene expression in the context of neuroAIDS. (A) Cartoon of HIV-Tat protein illustrating the mutation K50A. 2017 PloS one Figure HIV K50A 57 61 Tat 19 22 28640909 HIV-Tat regulates macrophage gene expression in the context of neuroAIDS. For comparison between Tat-Flag and K50ATat-Flag gene expression, Mann-Whitney tests were performed. 2017 PloS one Figure HIV K50A 36 40 Tat 23 26 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. The grey shaded area represents the monophyletic cluster with TDR mutation (T215C/D). 2017 Infection ecology & epidemiology Figure HIV T215C;T215D 76;76 83;83 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. (a) Immunoprecipitation of an HA-tagged IN_WT or IN_Mut with E212A/L213A substitutions co-transfected in the HEK293T cells together with Ku70_3xFLAG. 2017 Scientific reports Figure HIV E212A;L213A 61;67 66;72 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. (A) Plots for integration of HIV-1 WT and N74D within (left panel) or near (within 10kb of start site) (right panel) known genes. 2017 PLoS pathogens Figure HIV N74D 42 46 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. (A) Schematic depiction of the high through put screen; WT HIV-1 vector expresses GFP and N74D mutant HIV-1 vector expresses mCherry. 2017 PLoS pathogens Figure HIV N74D 90 94 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. (B) Jurkat cells were co-infected with WT and N74D vectors at an MOI of 0.1 in the presence of the indicated compounds and analysed 24h later. 2017 PLoS pathogens Figure HIV N74D 46 50 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. (B) Plots for integration of WT and N74D virus within (left panel) or near (right panel) genes susceptible to down-regulation by digoxin relative to their baseline bias to integrate within or near any gene. 2017 PLoS pathogens Figure HIV N74D 36 40 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. (D, E) Memory CD4+ T-cells were stimulated via CD3/CD28 Abs for 3 days and infected with VSV-G pseudotyped HIV-1 LAIDeltaenv WT (D) or N74D mutant (E), cells were cultured in media containing IL-2 in the presence or absence of the indicated doses of digoxin for additional 40 hours. 2017 PLoS pathogens Figure HIV N74D 135 139 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. (E) Jurkat cells were infected with HIV-1 LAIDeltaenv GFP WT or N74D at MOIs of 0.05-0.2 in the presence of the indicated concentrations of the anti-CD40L neutralizing antibody and analysed by flow cytometry 48h after infection to measure the percentage of GFP+ cells. 2017 PLoS pathogens Figure HIV N74D 64 68 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Digoxin inhibits HIV-1 infection more potently than N74D virus. 2017 PLoS pathogens Figure HIV N74D 52 56 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Plots for integration of WT and N74D virus within (left panel) or near (right panel) T-cell activation genes (A), cell metabolism genes (B) and hereditary disorder genes (C). 2017 PLoS pathogens Figure HIV N74D 32 36 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Three separate aliquots of Jurkat cells were independently infected with single cycle VSV-G pseudotyped HIV-1 LAIDeltaenv WT or N74D at an MOI of 0.2 in the presence of DMSO or 400nM digoxin. 2017 PLoS pathogens Figure HIV N74D 128 132 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. WT HIV-1 integrates more frequently than N74D within or near genes involved in T-cell activation and cell metabolism. 2017 PLoS pathogens Figure HIV N74D 41 45 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. (A) CD spectra of refp17, S75X, and p17R76G collected at room temperature at 2.5 muM in 10 mM phosphate buffer, pH 7.4. 2017 Scientific reports Figure HIV S75X 26 30 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. (A) Raji were plated in twelve-well plates and, after four days, medium was replaced by fresh medium with the indicated concentration of refp17, S75X and p17R76G. 2017 Scientific reports Figure HIV S75X 145 149 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. (B-D) Cells were treated for 5 min with 0.05, 0.1, 0.5 mug/ml of refp17 (B), S75X (C) and p17R76G (D). 2017 Scientific reports Figure HIV S75X 77 81 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. (B) At the top of the Figure, in the first row, the residues involved in the hydrogen bond network of p17 are shown and below the residues mutated in the variants S75X and p17R76G are indicated. 2017 Scientific reports Figure HIV S75X 163 167 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. (B) Thermal denaturation of refp17, S75X, and p17R76G at 10 muM in PBS, pH 7.4, as monitored at 222 nm by CD spectroscopy. 2017 Scientific reports Figure HIV S75X 36 40 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. (C) Measurement of the size of folded refp17, S75X and p17R76G viral matrix proteins by the technique of dynamic light scattering at room temperature. 2017 Scientific reports Figure HIV S75X 46 50 Matrix 69 75 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. (D) NMR spectra of refp17 (black), S75X (green), and p17R76G (red) showing their amide-amide NOEs. 2017 Scientific reports Figure HIV S75X 35 39 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Each amino acid residue of S75X not differing from refp17 sequence is represented by a dot. 2017 Scientific reports Figure HIV S75X 27 31 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Effect of refp17, S75X and p17R76G on B-cell activity. 2017 Scientific reports Figure HIV S75X 18 22 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Evolution of refp17, S75X and p17R76G protein structure by molecular dynamics simulations. 2017 Scientific reports Figure HIV S75X 21 25 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. On the contrary, either S75X or p17R76G induce the activation of Akt and maintains PTEN in an inactive state (C,D), as shown by the increased phosphorylation, verified by densitometric analysis and plotting of the pAkt/Akt and pPTEN/GAPDH. 2017 Scientific reports Figure HIV S75X 24 28 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Representation of KEGG pathways significantly regulated by S75X and p17R76G. 2017 Scientific reports Figure HIV S75X 59 63 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Representation of the putative signaling pathways involved in B-cell clonogenicity induced by interaction of S75X/p17R76G with p17R(s). 2017 Scientific reports Figure HIV S75X 109 113 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Sequence and hydrogen bond network of refp17 and S75X. 2017 Scientific reports Figure HIV S75X 49 53 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Stimulation of B cells with the clonogenic p17 proteins, S75X and p17R76G, induces the activation of several molecules involved in promoting cell survival, cell cycle progression and in inhibiting apoptosis, and STRING database and literature data mining were used to identify known and experimentally verified interactions. 2017 Scientific reports Figure HIV S75X 57 61 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Structure and stability of refp17, S75X and p17R76G. 2017 Scientific reports Figure HIV S75X 35 39 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. Docking of TatD60 with TAR; Inset-Ser46 of wild-type Tat with G48 of TAR at a distance of 5A, whereas Phe46 of TatD60 with G48 of TAR at a distance of 10A. 2017 Frontiers in microbiology Figure HIV I46S 34 39 Tat;Tat;Tat 11;53;111 14;56;114 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. (A) To validate the critical residues of GAPDH, D256R/K260E/K263E/E267R mutation (M6) was introduced in GAPDH. 2016 Biochemistry and biophysics reports Figure HIV D256R;E267R;K260E;K263E 48;66;54;60 53;71;59;65 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. (B) GAPDH constructs mutated in GAPDH-c in Y2H analysis. 2016 Biochemistry and biophysics reports Figure HIV Y2H 43 46 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. (B) Y2H analysis of interaction between M6 GAPDH and MA or CA-NTD. 2016 Biochemistry and biophysics reports Figure HIV Y2H 2 7 Matrix;Capsid 53;59 55;61 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. (C) Y2H analysis of N-terminal domain of GAPDH (GAPDH-n) or C-terminal domain of GAPDH (GAPDH-c) with p160gag-pol, Pr55gag, MA, CA, CA-NTD, CA-CTD, NC, p6 or Pol. 2016 Biochemistry and biophysics reports Figure HIV Y2H 2 7 Pol;Pol;NC;Gag;Matrix;Capsid;Capsid;Capsid;PR 110;158;148;152;124;128;132;140;115 113;161;150;154;126;130;134;142;117 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Y2H analysis of interaction between GAPDH and HIV-1 precursor proteins. 2016 Biochemistry and biophysics reports Figure HIV Y2H 0 3 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Y2H analysis of the interaction between C-terminal domain of GAPDH (GAPDH-c) and MA or CA-NTD. 2016 Biochemistry and biophysics reports Figure HIV Y2H 0 3 Matrix;Capsid 81;87 83;89 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. a Peptides containing the K43R mutation in the gag open reading frames (ORF) were used to detect T cell responses by the IFN-gamma ELISpot assay. 2017 Retrovirology Figure HIV K43R 26 30 Gag 47 50 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. a Replication of CH0131 T/F virus, the K43R mutant and the N323tc mutant were determined by culturing each virus independently in primary CD4+ T cell. 2017 Retrovirology Figure HIV K43R 39 43 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. b Identification of potential cryptic epitopes in all ORFs at the K43R mutation site. 2017 Retrovirology Figure HIV K43R 66 70 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. c T cell responses were detected with PBMCs from various days post screening and peptides containing potential cryptic epitopes at the K43R site by the IFN-gamma ELISpot assay. 2017 Retrovirology Figure HIV K43R 135 139 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Detection of T cell responses targeting the region containing the K43R mutation. 2017 Retrovirology Figure HIV K43R 66 70 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Fitness cost of the K43R mutation. 2017 Retrovirology Figure HIV K43R 20 24 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Fitness costs of the K43R mutant (c) and the N323tc mutant (e) were determined after three passages. 2017 Retrovirology Figure HIV K43R 21 25 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Relative fitness costs of the K43R mutant (b) and the N323tc mutant (d) were determined by measuring the proportions of both compared viruses in the same cell culture using the competitive PASS fitness assay. 2017 Retrovirology Figure HIV K43R 30 34 29017536 A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. The fixed K43R (a) and N323tc (b) mutations are indicated with bold letters among longitudinal sequences from subject CH0131. 2017 Retrovirology Figure HIV K43R 10 14 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. (A) Relative ST activities of G187R, F190Y, S217K and D185N mutants (wt = 100%) in the absence of DTG. 2017 Scientific reports Figure HIV D185N;F190Y;G187R;S217K 54;37;30;44 59;42;35;49 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. (B) ST activities of wt, G187R, F190Y and S217K proteins as a function of DTG concentration (expressed for each protein as percentages of the value obtained for the condition without DTG). 2017 Scientific reports Figure HIV F190Y;G187R;S217K 32;25;42 37;30;47 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. Strand transfer (ST) activities and measurements of resistance to DTG of G187R, F190Y and S217K INPFV mutants. 2017 Scientific reports Figure HIV F190Y;G187R;S217K 80;73;90 85;78;95 29070877 Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence. The results show that DTG displays similar affinities for wt and F190Y INs (Kd 0.4 muM), in contrast to that observed for G187R and S217K resistant mutants or the catalytic D185N mutant (the DNA-binding properties of mutants are shown in Supplementary. 2017 Scientific reports Figure HIV D185N;F190Y;G187R;S217K 173;65;122;132 178;70;127;137 IN 71 74 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. L33F acts as a molecular anchor that restricts movement of the 30s and 80s loops. 2015 Biochemistry and biophysics reports Figure HIV L33F 0 4 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. L33F fills the hydrophobic pocket more completely than L33. 2015 Biochemistry and biophysics reports Figure HIV L33F 0 4 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. L33F prevents movement of the 30s and 80s loops towards the active site as in the WT and MDR769 structures. 2015 Biochemistry and biophysics reports Figure HIV L33F 0 4 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Reduced flap interactions due to L33F anchoring. 2015 Biochemistry and biophysics reports Figure HIV L33F 33 37 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The inset in (C) shows the 2Fo- Fc map for DRV and the 80s loop in the L33F structure contoured at 0.5sigma in order that the density around DRV is shown. 2015 Biochemistry and biophysics reports Figure HIV L33F 71 75 29176596 Quenching protein dynamics interferes with HIV capsid maturation. a Clustering analysis of the MD trajectory of CA-SP1 WT (left) and CA-SP1(T8I) mutant (right) identified six major sub-populations. 2017 Nature communications Figure HIV T8I 74 77 SP1;SP1;Capsid;Capsid 49;70;46;67 52;73;48;69 29176596 Quenching protein dynamics interferes with HIV capsid maturation. b Sequential assignment walk for a stretch of CA-SP1(T8I) residues (SP1 residues E2-S5). 2017 Nature communications Figure HIV T8I 53 56 SP1;SP1;Capsid 49;68;46 52;71;48 29176596 Quenching protein dynamics interferes with HIV capsid maturation. b Stride plots of secondary structure for each chain along with the MD trajectories for CA CTD-SP1 WT (top), and CA CTD-SP1(T8I) mutant (bottom). 2017 Nature communications Figure HIV T8I 124 127 SP1;SP1;Capsid;Capsid 95;120;88;113 98;123;90;115 29176596 Quenching protein dynamics interferes with HIV capsid maturation. b, c The CTD tail (V221-end)SP1 region exhibits a dynamic equilibrium between random coil and helical conformations in CA CTD-SP1 WT, whereas in the CA CTD-SP1(T8I) mutant the dynamics are greatly attenuated and the helical content is increased. 2017 Nature communications Figure HIV T8I 160 163 SP1;SP1;SP1;Capsid;Capsid 28;126;156;119;149 31;129;159;121;151 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Bottom: CA(A92E)-SP1 NL4-3 (red), CA-SP1 HXB2 (blue), and CA-SP1(T8I) NL4-3 (gray). 2017 Nature communications Figure HIV A92E;T8I 11;65 15;68 SP1;SP1;SP1;Capsid;Capsid;Capsid 17;37;61;8;34;58 20;40;64;10;36;60 29176596 Quenching protein dynamics interferes with HIV capsid maturation. c Helix/coil probability of the CTD tail (V221-end)SP1 subdomain averaged over the MD trajectories: CTD-SP1 WT (top) and CTD-SP1(T8I) (bottom). 2017 Nature communications Figure HIV T8I 129 132 SP1;SP1;SP1 51;104;125 54;107;128 29176596 Quenching protein dynamics interferes with HIV capsid maturation. d Correlation of MAS NMR chemical shifts and SHIFTX2-predicted shifts from the MD trajectory seeded from the X-ray structure (PDB: 5I4T): CTD-SP1 WT (left) and CTD-SP1(T8I) (right). 2017 Nature communications Figure HIV T8I 168 171 SP1;SP1;Matrix 142;164;17 145;167;19 29176596 Quenching protein dynamics interferes with HIV capsid maturation. I, II, III: sum of 13Calpha,15N chemical shift perturbations (CSP): CA NL4-3 and CA-SP1(T8I) NL4-3 (orange), CA(A92E) NL4-3 and CA(A92E)-SP1 NL4-3 (brown), CA HXB2, and CA-SP1 HXB2 (blue). 2017 Nature communications Figure HIV A92E;A92E;T8I 112;131;88 116;135;91 SP1;SP1;SP1;Capsid;Capsid;Capsid;Capsid;Capsid;Capsid 84;137;172;68;81;109;128;156;169 87;140;175;70;83;111;130;158;171 29176596 Quenching protein dynamics interferes with HIV capsid maturation. IV: Plot of the 13Calpha-15N backbone peak intensity ratio (CA-SP1(T8I) NL4-3/CA NL4-3; gray) vs. 2017 Nature communications Figure HIV T8I 67 70 SP1;Capsid;Capsid 63;60;78 66;62;80 29176596 Quenching protein dynamics interferes with HIV capsid maturation. j Assembly assay of CA-SP1(T8I) NL4-3 and CA NL4-3 for different concentrations of NaCl. 2017 Nature communications Figure HIV T8I 27 30 SP1;Capsid;Capsid 23;20;42 26;22;44 29176596 Quenching protein dynamics interferes with HIV capsid maturation. k TEM images of tubular assemblies of CA(A92E) and CA(A92E)-SP1 variants. 2017 Nature communications Figure HIV A92E;A92E 41;54 45;58 SP1;Capsid;Capsid 60;38;51 63;40;53 29176596 Quenching protein dynamics interferes with HIV capsid maturation. One chain is colored in blue (CA-CTD) and green (SP1) to illustrate the differences in secondary structure present in the SP1 region: predominantly random coil in CA-SP1 WT and significantly increased helical content in CA-SP1(T8I). 2017 Nature communications Figure HIV T8I 227 230 SP1;SP1;SP1;SP1;Capsid;Capsid;Capsid 49;122;166;223;30;163;220 52;125;169;226;32;165;222 29176596 Quenching protein dynamics interferes with HIV capsid maturation. residue number for CypA loop residues in CA HXB2, CA NL4-3, CA(A92E) NL4-3, CA(A92E)-SP1 NL4-3, and CA-SP1(T8I) NL4-3. 2017 Nature communications Figure HIV A92E;A92E;T8I 63;79;107 67;83;110 SP1;SP1;Capsid;Capsid;Capsid;Capsid;Capsid 85;103;41;50;60;76;100 88;106;43;52;62;78;102 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The CA-SP1(T8I) mutant exhibits the same order of magnitude attenuation of loop dynamics as previously observed in the CA(A92E) escape mutant . 2017 Nature communications Figure HIV A92E;T8I 122;11 126;14 SP1;Capsid;Capsid 7;4;119 10;6;121 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The CA-SP1(T8I) mutant exhibits the same order of magnitude attenuation of loop dynamics as previously observed in the CA(A92E) escape mutant. 2017 Nature communications Figure HIV A92E;T8I 122;11 126;14 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The T8I mutation in SP1 mimics the presence of maturation inhibitors (MI) in abolishing SP1 cleavage. 2017 Nature communications Figure HIV T8I 4 7 SP1;SP1 20;88 23;91 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Top: CA NL4-3 (orange) and CA-SP1(T8I) NL4-3 (gray). 2017 Nature communications Figure HIV T8I 34 37 SP1;Capsid;Capsid 30;5;27 33;7;29 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. B, midpoint anti-trimer binding titers were determined in a D7324-capture ELISA based on the BG505 SOSIP.664 and SOSIP.v5.2 S306L/R308L trimers. 2018 The Journal of biological chemistry Figure HIV R308L;S306L 130;124 135;129 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. BG505.T332N Env-pseudoviruses were obtained via transfection of 293T HEK cells. 2018 The Journal of biological chemistry Figure HIV T332N 6 11 Env 12 15 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. C, midpoint binding titers were determined in a peptide ELISA using a cyclized BG505 V3 peptide (WT) and a variant containing the S306L, R308L, and A316W changes that are present in the SOSIP.v5.2 S306L/R308L trimer. 2018 The Journal of biological chemistry Figure HIV A316W;R308L;R308L;S306L;S306L 148;137;203;130;197 153;142;208;135;202 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. D-F, midpoint neutralizing titers against the autologous tier 2 virus BG505.T332N (D) and the heterologous tier 1A viruses SF162 and MW965.26 (E and F) were determined using the TZM-bl assay. 2018 The Journal of biological chemistry Figure HIV T332N 76 81 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. D, 2D class averages of NS-EM analyses of the SOSIP.v4.1 S306L/R308L (3) and SOSIP.v5.2 S306L/R308L (5). 2018 The Journal of biological chemistry Figure HIV R308L;R308L;S306L;S306L 63;94;57;88 68;99;62;93 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Immunogenicity of BG505 SOSIP.v5.2 S306L/R308L trimers in rabbits. 2018 The Journal of biological chemistry Figure HIV R308L;S306L 41;35 46;40 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. In A-E, the trimer variants are numbered as follows: 1, SOSIP.664; 2, SOSIP.v4.1; 3, SOSIP.v4.1 S306L/R308L; 4, SOSIP.v5.2; 5, SOSIP.v5.2 S306L/R308L. 2018 The Journal of biological chemistry Figure HIV R308L;R308L;S306L;S306L 102;144;96;138 107;149;101;143 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. In C, residues Ser306, Arg308, and Ala316 are shown as sticks, whereas D shows the impact of introducing the S306L, R308L, and A316W substitutions (shown in blue) by in silico mutagenesis. 2018 The Journal of biological chemistry Figure HIV A316W;R308L;S306L 127;116;109 132;121;114 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Infection of TZM-bl cells by various BG505.T332N Env-pseudovirus variants containing the S306L, R308L, and/or A316W substitutions was assessed. 2018 The Journal of biological chemistry Figure HIV A316W;R308L;S306L;T332N 110;96;89;43 115;101;94;48 Env 49 52 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The hydrophobic V3 mutations, S306L, R308L, and A316W, were introduced into the crystal structure by in silico mutagenesis using PyMOL and are depicted in blue. 2018 The Journal of biological chemistry Figure HIV A316W;R308L;S306L 48;37;30 53;42;35 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The rabbits were immunized with 22 mug of the BG505 SOSIP.v5.2 S306L/R308L and comparator proteins at weeks 0, 4, and 20, and Ab responses were measured at week 22. 2018 The Journal of biological chemistry Figure HIV R308L;S306L 69;63 74;68 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. The SOSIP.664 mutations are indicated in red, the SOSIP.v4.1 mutations (E64K and A316W) are in blue, the SOSIP.v5.2 mutations (A73C-A561C) are in purple, and the new hydrophobic V3 mutations are in light brown. 2018 The Journal of biological chemistry Figure HIV A316W;A561C;A73C;E64K 81;132;127;72 86;137;131;77 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. (B) Average SBRs of the lateral flow ELISA when varying copy numbers of DNA containing the M184V mutation are used as input to the RPA reaction (n = 3, *n = 2). 2018 Analytical biochemistry Figure HIV M184V 91 96 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. Results of the lateral flow assay for three separate experiments using wild type or M184V DNA. 2018 Analytical biochemistry Figure HIV M184V 84 89 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. The RPA assay amplifies a region that contains several major drug resistance mutations, K103N, V106M, Y181C, and M184V (wild type codons denoted with red lines). 2018 Analytical biochemistry Figure HIV K103N;M184V;V106M;Y181C 88;113;95;102 93;118;100;107 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Asterisks indicate the detection of V179I/A as applicable. 2018 PloS one Figure HIV V179A;V179I 36;36 43;43 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Sequences presenting the G190A mutation are highlighted within the light grey shaded square. 2018 PloS one Figure HIV G190A 25 30 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. Blue bars represent previously reported values, obtained using M13mp2-based assays measuring the accuracy of DNA-dependent DNA synthesis of HIV-1BH10, HIV-1ESP49, AMV, and MLV, O_K65R/V75I and O_K65R RTs. 2018 Scientific reports Figure HIV K65R;K65R;V75I 179;195;184 183;199;188 RT 200 203 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. RTs included are those of WT HIV-1BH10 (pink), HIV-1ESP49 (purple), AMV (red), and MLV (green), and mutants O_K65R/V75I (blue) and O_K65R (brown). 2018 Scientific reports Figure HIV K65R;K65R;V75I 110;133;115 114;137;119 RT 0 3 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. (B, C) Influences of MBP SigP position on self-degradation of released mature PR (panel B) and on H69D autoprocessing activity (panel C). 2018 PloS one Figure HIV H69D 98 102 PR 78 80 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. (B, C) Western blot assessment of MBP SigP's influences on mature PR self-degradation (panel B) and H69D autoprocessing (panel C) in transfected HeLa cells. 2018 PloS one Figure HIV H69D 100 104 PR 66 68 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. (C) Influences of SigL and SigP on H69D autoprocessing activity. 2018 PloS one Figure HIV H69D 35 39 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. (D, E) Representative images of HeLa cells transfected with plasmids encoding for the D25N GFP fusion without (panel D) or with (panel E) MBP SigP. 2018 PloS one Figure HIV D25N 86 90 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Autoprocessing of F56C precursors in the context of GST (A) and L-MBP (B) fusion. 2018 PloS one Figure HIV F56C 18 22 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Detection and quantification of PRs in viral particles made by the WT and F56C/L63P proviral constructs. 2018 PloS one Figure HIV F56C;L63P 74;79 78;83 PR 32 35 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. H69D mutation abolishes autoprocessing in the context of L-MBP/F-MBP fusion independent of p6* sequences. 2018 PloS one Figure HIV H69D 0 4 Gag 91 93 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. 7a) at 2dpi (n = 9, 9, 3 for CV, CLV, and CLV-Q65R, respectively). 2018 Retrovirology Figure HIV Q65R 46 50 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. b Production of lentiviral particles with CV, CLV, and CLV-Q65R. 2018 Retrovirology Figure HIV Q65R 59 63 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. CV, CLV, and CLV-Q65R incorporated lentivirus was infected into U2OS/2-6-3 cells and subjected to qPCR analysis. 2018 Retrovirology Figure HIV Q65R 17 21 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. d Mobility of H2B was not increased by the Q65R mutant of Vpr. 2018 Retrovirology Figure HIV Q65R 43 47 Vpr 58 61 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Differentiated MM-6 cells were infected with NL4-3/D64A virus for 1 day, and then subjected to neutral comet assay. 2018 Retrovirology Figure HIV D64A 51 55 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. e Defect of the Q65R mutant for RPA70 loading was rescued by TSA. 2018 Retrovirology Figure HIV Q65R 16 20 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. For this experiment, we newly established cell lines (HT1080vRxt-Vpr), in which expression of Vpr-Wt (lanes 3 and 4), Vpr-Q65R (lanes 5 and 6), Vpr-R77Q (lanes 7 and 8), Vpr-R80A (lanes 9 and 10) and Vpr-Ct4RA (lanes 11 and 12) can be controlled by the tetracycline promoter, and ubiquitination of H2B on K120 was examined after Dox treatment (5 mug/ml, 2 days). 2018 Retrovirology Figure HIV Q65R;R77Q;R80A 122;148;174 126;152;178 Vpr;Vpr;Vpr;Vpr;Vpr;Vpr 65;94;118;144;170;200 68;97;121;147;173;203 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. The cells were then infected with NL4-3/D64A/R- virus and subjected to qPCR analysis at 2dpi. 2018 Retrovirology Figure HIV D64A;D64R 40;40 44;44 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. (a) RTQ151M:DNA:ETV-TP. 2018 Scientific reports Figure HIV Q151M 6 11 RT 4 6 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. (b) Ribbon representation showing the overall structures of the RTQ151M:DNA:ETV-TP ternary complex, and (c) the superimposition of the RTQ151M:DNA binary and RTQ151M:DNA:ETV-TP ternary complexes. 2018 Scientific reports Figure HIV Q151M;Q151M;Q151M 66;137;160 71;142;165 RT;RT;RT 64;135;158 66;137;160 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. RTQ151M:DNA complex preparation and structure determination. 2018 Scientific reports Figure HIV Q151M 2 7 RT 0 2 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. (A and B) rHIVWT, rHIVV32I/I54M, rHIVL33F/I84V, and rHIVV32I/L33F/I54M/I84V (A) and rHIVV32I, rHIVL33F, rHIVI54M, and rHIVI84V (B) were propagated in the presence of increasing concentrations of DRV in MT-4 cells. 2018 mBio Figure HIV I54M;I84V;L33F;I54M;I84V 66;71;61;27;42 70;75;65;31;46 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. (B) Absence of the V32I substitution in two infectious clones, rHIVWT and rHIVL33F, which were selected with DRV over 50 weeks. 2018 mBio Figure HIV V32I 19 23 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. (B) The locations of V32, L33F, M46, I54, A71, and I84 are shown in the dimerized protease. 2018 mBio Figure HIV L33F 26 30 PR 82 90 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. (C and D) The replication profiles of HIVWT versus HIVV32I and HIVV32I versus HIVV32I/A71V in the absence (solid line) or presence (dashed line) of 3 nM DRV were examined using the competitive HIV replication assay. 2018 mBio Figure HIV A71V;V32I 86;81 90;85 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. COS-7 cells were also cotransfected with plasmids encoding either of HIVNL4-3 clones producing CFP- or YFP-tagged V32I-carrying protease (HIVV32I). 2018 mBio Figure HIV V32I 114 118 PR 128 136 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Emergence of the V32I substitution during the selection of highly DRV-resistant HIV-1 variants but not in HIVWT and HIVL33F. 2018 mBio Figure HIV V32I 17 21 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In the selection with DRV, proviral DNA was extracted at week 50 for HIVWT and HIVL33F, at week 36 for HIVV32I, at weeks 7, 24, and 36 for HIVI54M, at weeks 8, 17 and 29 for HIVI84V, at week 22 for HIVV32I/I54M, at week 26 for HIVL33F/I84V, and at week 17 for HIVV32I/L33F/I54M/I84V. 2018 mBio Figure HIV I54M;I84V;L33F;V32I;I54M;I84V 273;278;268;263;206;235 277;282;272;267;210;239 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Note that rHIVM46I apparently failed to develop DRV resistance, while rHIVA71V rapidly developed DRV resistance, acquiring the V32I substitution. 2018 mBio Figure HIV V32I 127 131 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Note that the V32I substitution did not emerge in either of the virus populations. 2018 mBio Figure HIV V32I 14 18 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Replication profiles of rHIVWT, rHIVV32I, and rHIVV32I/A71V were examined. 2018 mBio Figure HIV A71V 55 59 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. rHIVA71V acquired V32I and eventually became resistant to DRV. 2018 mBio Figure HIV V32I 18 22 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. rHIVA71V rapidly develops DRV resistance, acquiring the V32I substitution. 2018 mBio Figure HIV V32I 56 60 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. rHIVI84V quickly acquired A71V, subsequently acquired V32I, and became resistant to DRV. 2018 mBio Figure HIV A71V;V32I 26;54 30;58 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. rHIVL33F/I84V continued to propagate in the presence of DRV, acquired V32I but without acquiring A71V, and became resistant to DRV. 2018 mBio Figure HIV A71V;I84V;V32I 97;9;70 101;13;74 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. rHIVL33F/I84V's acquisition of high-level DRV resistance despite the absence of A71V strongly suggest that its DRV resistance acquisition involved alternate albeit unidentified pathway of DRV resistance development. 2018 mBio Figure HIV A71V;I84V 80;9 84;13 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. rHIVV32I and rHIVI54M relatively rapidly acquired A71V, and rHIVI54M subsequently acquired V32I. 2018 mBio Figure HIV A71V;V32I 50;91 54;95 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The failure of rHIVV32I replication in the presence of 3 nM DRV suggests that rHIVV32I is more susceptible to DRV than rHIVWT and rHIVV32I/A71V are. 2018 mBio Figure HIV A71V 139 143 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The impact of four amino acid substitutions, V32I, L33F, I54M, and I84V, on the development of DRV resistance was examined. 2018 mBio Figure HIV I54M;I84V;L33F;V32I 57;67;51;45 61;71;55;49 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. To confirm the absence of V32I, HIVWT-WK50 and HIVL33F-WK50 were further cloned (20 clones), and each clone generated was sequenced. 2018 mBio Figure HIV L33F;V32I 50;26 54;30 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Upon DRV selection, rHIVV32I/I54M quickly acquired A71V and became highly resistant to DRV. 2018 mBio Figure HIV A71V;I54M;V32I 51;29;24 55;33;28 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. V32I reduces the viral fitness of HIV-1, while A71V recovers the compromised fitness. 2018 mBio Figure HIV A71V;V32I 47;0 51;4 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Each group displays box-and-whisker plots of interquartile FC ranges for all samples in the category (white), samples without K103N (shaded) and samples containing K103N (diagonal stripes). 2018 Antiviral chemistry & chemotherapy Figure HIV K103N;K103N 126;164 131;169 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. FC resistance was evaluated based on the contribution of the number of RPV-associated mutations (L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) per sample with and without K103N. 2018 Antiviral chemistry & chemotherapy Figure HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;K103N;L100I;M230I;M230L;V179L;Y181C;Y181I;Y181V;Y188L 113;113;113;113;113;160;153;104;104;207;97;170;170;128;135;135;135;146 126;126;126;126;126;165;158;111;111;212;102;177;177;133;144;144;144;151 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. The first available specimen from PIC 90629 was observed to have a dual HIV pol population, with approximately 50% of viral variants resistant to lamivudine/emtricitabine (M184V) and 50% drug-susceptible (see Table 2). 2018 PLoS medicine Figure HIV M184V 172 177 Pol 76 79 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. (C) WT or E300R RTp51/p66 heterodimer was purified from E. 2018 mBio Figure HIV E300R 10 15 RT 16 18 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. (D) Lysates of HEK293T cells expressing the indicated combinations of WT or E300R RTp51 or RTp66 (top) were immunoprecipitated with an anti-eEF1A antibody. 2018 mBio Figure HIV E300R 76 81 RT;RT 82;91 84;93 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. A BLI assay on the Octet Red machine was used to determine the association (Ka) and dissociation (Kd) constants of purified WT and E300R mutant RT heterodimer with biotinylated eEF1A immobilized on a streptavidin-coated biosensor. 2018 mBio Figure HIV E300R 131 136 RT 144 146 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Characterization of HIV-1 harboring E297R, E298R, and E300R mutations. 2018 mBio Figure HIV E297R;E298R;E300R 36;43;54 41;48;59 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Data are the mean number of relative BRET units compared to the WT for the RTp66 mutants (n = 7 for WT, E297R, E298R, and E300R; n = 3 for D250R and L303A), and error bars represent the standard error of the mean. 2018 mBio Figure HIV D250R;E297R;E298R;E300R;L303A 139;104;111;122;149 144;109;116;127;154 RT 75 77 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. ERT assays were performed with similar amounts of WT and E300R HIV-1 virions incubated with or without dNTPs for 6 h, and qPCR was used to measure ssDNA (D) and first strand transfer DNA (E). 2018 mBio Figure HIV E300R 57 62 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Molecular dynamic simulations of the HIV-1 RTp66 domain showing ribbon schematics and surface representation of the thumb domain of the WT (C), the W252A mutant (D), and the L303A mutant (E). 2018 mBio Figure HIV L303A;W252A 174;148 179;153 RT 43 45 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. W252A and L303A mutations disrupt a surface-exposed acidic region in the alpha-J helix of the HIV-1 thumb domain. 2018 mBio Figure HIV L303A;W252A 10;0 15;5 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. For simplicity, M184V/I mutations were combined with thymidine analog mutations (TAMs). 2018 Clinical infectious diseases Figure HIV M184I;M184V 16;16 23;23 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. HIV-infected adults with CSF escape and M184V/I mutations on genotypic resistance tests in CSF and/or plasma were identified from published studies (n = 34). 2018 Clinical infectious diseases Figure HIV M184I;M184V 40;40 47;47 HIV infections 0 12 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Schematic diagram showing the predicted resistance to nucleoside reverse transcriptase inhibitor with M184V/I mutations. 2018 Clinical infectious diseases Figure HIV M184I;M184V 102;102 109;109 NRTI 54 86 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. (B) Conformation of residues 45_B, 76_B and 32_B of PR1 (coloured blue, PDB code: 1HPV), PR2 (coloured red, PDB code: 3S45), PR1L76M mutants (coloured green) and PR1V32I+L76M mutants (coloured yellow). 2018 Scientific reports Figure HIV L76M 170 174 PR;PR;PR;PR 89;52;125;162 92;55;128;165 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. *Among the 160 mutant structures with the mutation T31S, 68 are in cluster 1 (42% = 68/160). 2018 Scientific reports Figure HIV T31S 51 55 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Cyan dots represent the van der Waals sphere of the I32_B_CE atom of PR1V32I+L76M mutant number 4. 2018 Scientific reports Figure HIV L76M 77 81 PR 69 72 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Modelled probability of viral suppression in ART-experienced patients in terms of time since treatment switch following detection of the Q151M mutation for patients with a baseline viral load of (a) 2000 copies/mL ( 10th centile), (b) 40,000 copies/mL ( 50th centile) or (c) 500,000 copies/mL ( 90th centile). 2018 AIDS research and therapy Figure HIV Q151M 137 142 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Posterior mean values and 95% credibility intervals for (a) log-odds ratios in the matched case-control analysis investigating factors associated with the occurrence of the Q151M mutation and (b) log-hazard ratios in the Cox regression for confirmed viral suppression following treatment change after detection of Q151M mutation. 2018 AIDS research and therapy Figure HIV Q151M;Q151M 173;314 178;319 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Prevalence of (a) the Q151M mutation and (b) the T69i mutation per patient by calendar year of sequencing (patients can be included in multiple calendar years, but are only counted once per year), according to whether the patient was ART experienced (black circle) or naive (orange circle) at the time of blood sample. 2018 AIDS research and therapy Figure HIV Q151M 22 27 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. 293T cells were co-transfected with pCI-His-hUbi plasmid and WT Flag-Tat, Flag-Tat S16A, Flag-Tat S46A expressing plasmids. 2018 Retrovirology Figure HIV S16A;S46A 83;98 87;102 Tat;Tat;Tat 69;79;94 72;82;97 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. 293T cells were transfected and processed as in a except WT Flag-Tat, Flag-Tat S16D, Flag-Tat S46D and Flag-Tat K71A expressing plasmids were used. 2018 Retrovirology Figure HIV K71A;S16D;S46D 112;79;94 116;83;98 Tat;Tat;Tat;Tat 65;75;90;108 68;78;93;111 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. 293T cells were transfected with Flag-Tat vectors expressing WT Tat, Tat S16A, Tat S16D, Tat S46A and Tat S46D mutants. 2018 Retrovirology Figure HIV S16A;S16D;S46A;S46D 73;83;93;106 77;87;97;110 Tat;Tat;Tat;Tat;Tat;Tat 38;64;69;79;89;102 41;67;72;82;92;105 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. 293T cells were transfected with plasmids expressing WT Flag-Tat, Flag-Tat S16A or Flag-Tat S46A. 2018 Retrovirology Figure HIV S16A;S46A 75;92 79;96 Tat;Tat;Tat 61;71;88 64;74;91 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. 293T cells were transfected with plasmids expressing WT Flag-Tat, Flag-Tat S16A, Flag-Tat S16D, Flag-Tat S46A and Flag-Tat S46D and with cyclin T1 expressing vector. 2018 Retrovirology Figure HIV S16A;S16D;S46A;S46D 75;90;105;123 79;94;109;127 Tat;Tat;Tat;Tat;Tat 61;71;86;101;119 64;74;89;104;122 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. a Spatial superposition of the CDK9/Cyclin T1/Tat complexes with non-phosphorylated Tat (S16&S46) and Tat phosphorylated on Ser-16 and Ser-46 (S16P&S46P) at 20 ns MD time, protein main chains are shown as follows: Cyclin T1:in blue and grey colors, CDK9:in green and carrot colors and Tat:in yellow and cyan colors, respectively. 2018 Retrovirology Figure HIV S16P;S46P 143;148 148;152 Tat;Tat;Tat;Tat 46;84;102;285 49;87;105;288 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. a Tat S46A mutation decreased Tat ubiquitination. 2018 Retrovirology Figure HIV S46A 6 10 Tat;Tat 2;30 5;33 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. b Tat S46D mutation decreased Tat ubiquitination. 2018 Retrovirology Figure HIV S46D 6 10 Tat;Tat 2;30 5;33 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. b, c Replication of VSVg pseudotyped pNL4-3.Luc.R-E-vectors with WT and mutant Tat S16A, S16E, S46A and S46E sequences. 2018 Retrovirology Figure HIV S16A;S16E;S46A;S46E 83;89;95;104 87;93;99;108 Tat 79 82 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. e 293T cells were transfected with vectors expressing EGFP, WT Tat-EGFP, Tat S16A-GEFP, Tat S16E-EGFP, Tat S46A-EGFP and Tat-S46E-EGFP. 2018 Retrovirology Figure HIV S16A;S16E;S46A;S46E 77;92;107;125 81;96;111;129 Tat;Tat;Tat;Tat;Tat 63;73;88;103;121 66;76;91;106;124 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Effect of Tat S16A, S16D, S46A and S46D mutations on the interaction with TAR RNA and association with cyclin T1. 2018 Retrovirology Figure HIV S16A;S16D;S46A;S46D 14;20;26;35 18;24;30;39 Tat 10 13 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Flag-tagged Tat, WT and S16A and S46A mutants were expressed in 293T cells and metabolically labeled with (32P) orthophosphate. 2018 Retrovirology Figure HIV S16A;S46A 24;33 28;37 Tat 12 15 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. In b, luciferase activity for WT, S16E and S46E viruses was normalized to p24. 2018 Retrovirology Figure HIV S16E;S46E 34;43 38;47 p24 74 77 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Lane 3, Tat S16A mutant. 2018 Retrovirology Figure HIV S16A 12 16 Tat 8 11 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Lane 4, Tat S46A mutant. 2018 Retrovirology Figure HIV S46A 12 16 Tat 8 11 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. One individual (PID 50) was also primarily infected with this virus as a 2002 sequence obtained prior to therapy contained Y181C + L90M (indicated in red with an open triangle) and later developed K103N (indicated in black with a closed triangle) after receiving multiple nucleoside reverse transcriptase inhibitor regimens followed by tenofovir/emtricitabine/efavirenz in combination with atazanavir/ritonavir and then raltegravir. 2019 Clinical infectious diseases Figure HIV K103N;L90M;Y181C 197;131;123 202;135;128 NRTI 272 304 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. This ART-experienced individual appeared to acquire Y181C + L90M plus K70R in 1999 (sequence followed by an asterisk). 2019 Clinical infectious diseases Figure HIV K70R;L90M;Y181C 70;60;52 74;64;57 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. Time-scale analysis of the large virus cluster containing viruses with the nonnucleoside reverse transcriptase inhibitor resistance mutation Y181C and the protease inhibitor resistance mutation L90M. 2019 Clinical infectious diseases Figure HIV L90M;Y181C 194;141 198;146 NNRTI;PR 75;155 110;163 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. Viruses from 16 ART-naive individuals with Y181C + L90M are indicated in red, and 4 viruses with the same mutations from an ART-experienced individual are indicated in blue (PID 52). 2019 Clinical infectious diseases Figure HIV L90M;Y181C 51;43 55;48 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. a: Estimated probability of being free from virological failure (VF) with dual therapy (M184V groups based on the hGRT). 2018 Open forum infectious diseases Figure HIV M184V 88 94 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. b: Estimated probability of being free from virological failure (VF) in the overall population of dual therapy and in patients with shorter time of viral suppression (M184V groups based on the hGRT). 2018 Open forum infectious diseases Figure HIV M184V 167 173 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. c: Estimated probability of being free from treatment discontinuation (TD) with dual therapy (M184V groups based on the hGRT). 2018 Open forum infectious diseases Figure HIV M184V 94 100 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. d: Estimated probability of being free from virological blips (VB) with dual therapy (M184V groups based on the hGRT). 2018 Open forum infectious diseases Figure HIV M184V 86 92 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (A) Comparison of the size exclusion chromatography profiles of the 16055 NFL trimers possessing the I559P and L555P substitutions following lectin-affinity purification. 2018 Frontiers in immunology Figure HIV I559P;L555P 101;111 106;116 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (A) Size exclusion chromatography (SEC) profiles of 16055 NFL TD 2CC+ D4K I559P and L555P trimers following lectin-affinity purification. 2018 Frontiers in immunology Figure HIV I559P;L555P 74;84 79;89 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (A) Size exclusion chromatography profiles of 16055 NFL TD 2CC+ D4K I559P and L555P trimers after rEK cleavage (w/ rEK). 2018 Frontiers in immunology Figure HIV I559P;L555P 68;78 73;83 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (B) Comparison of 2D class averages from negative stain electron microscopy of 16055 NFL TD 2CC+ D4K I559P and L555P trimers. 2018 Frontiers in immunology Figure HIV I559P;L555P 101;111 106;116 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (B) Comparison of 2D class averages from negative stain electron microscopy of cleaved 16055 NFL TD 2CC+ D4K I559P and L555P trimers (w/ rEK). 2018 Frontiers in immunology Figure HIV I559P;L555P 109;119 114;124 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (B) Differential scanning calorimetry measurements of 16055 NFL trimers possessing either I559P or L555P. 2018 Frontiers in immunology Figure HIV I559P;L555P 90;99 95;104 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (B) Linear schematic diagram of the NFL with I559P or L555P, A501C-L663C (CC2), or TD CC+ substitutions. 2018 Frontiers in immunology Figure HIV A501C;I559P;L555P;L663C 61;45;54;67 66;50;59;72 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (C) 2D class averages from negative stain electron microscopy (NS-EM) of 16055 NFL L555P trimers purified by negative selection using GE136. 2018 Frontiers in immunology Figure HIV L555P 83 88 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (D) Differential scanning calorimetry measurements of 16055 NFL TD 2CC+ D4K I559P and L555P trimers. 2018 Frontiers in immunology Figure HIV I559P;L555P 76;86 81;91 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (D) Differential scanning calorimetry measurements of cleaved 16055 NFL TD 2CC+ D4K I559P and L555P trimers (w/ rEK). 2018 Frontiers in immunology Figure HIV I559P;L555P 84;94 89;99 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. (E) Comparison of ELISA binding properties of selected mAbs to 16055 NFL TD 2CC+ D4K I559P and L555P trimers. 2018 Frontiers in immunology Figure HIV I559P;L555P 85;95 90;100 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Biochemical, biophysical, and antigenic characterization of 16055 NFL TD 2CC+ D4K I559P and L555P trimers after recombinant enterokinase (rEK) cleavage. 2018 Frontiers in immunology Figure HIV I559P;L555P 82;92 87;97 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Biochemical, biophysical, and antigenic characterization of 16055 NFL TD 2CC+ D4K trimers possessing the I559P and L555P substitutions. 2018 Frontiers in immunology Figure HIV I559P;L555P 105;115 110;120 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Biochemical, biophysical, and antigenic characterization of 16055 NFL trimers possessing the L555P substitution. 2018 Frontiers in immunology Figure HIV L555P 93 98 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. L555P is indicated with light pink spheres and I559P by the magenta spheres. 2018 Frontiers in immunology Figure HIV I559P;L555P 47;0 52;5 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The A501C-L663C cysteine pair forming a putative inter-protomer disulfide bond between the first and second protomers is shown in yellow and green spheres in the lower-left, close-up view. 2018 Frontiers in immunology Figure HIV A501C;L663C 4;10 9;15 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The data for 16055 NFL I559P are adapted as previously reported. 2018 Frontiers in immunology Figure HIV I559P 23 28 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. (A-C) Cell cycle analysis of 293T cells expressing Vpr WT (B) or Vpr H71R. 2018 Nucleic acids research Figure HIV H71R 69 73 Vpr;Vpr 51;65 54;68 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. (A) The level of L1 ORF1p in presence of Vpr WT and H71R mutant. 2018 Nucleic acids research Figure HIV H71R 52 56 Vpr 41 44 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. (A) Western blotting of human ORF1p, HA-Vpr, p21 or S6 protein as a loading control in RNP prepared from 293T cells transfected with the indicated plasmids: pCEP4 and pcDNA3-HA (HA) empty vectors (-), pJM105/L1.3 and pcDNA3-HA (-) or pJM101/L1.3 together with pcDNA3-HA (-), pcDNA3-HA-Vpr WT, pcDNA3-HA-Vpr H71R, or pcDNA3 p21. 2018 Nucleic acids research Figure HIV H71R 307 311 Vpr;Vpr;Vpr 40;285;303 43;288;306 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. (B) Protein expression level of L1 ORF1p and hrGFP in presence of Vpr WT and H71R mutant. 2018 Nucleic acids research Figure HIV H71R 77 81 Vpr 66 69 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. (D) Protein expression levels of wild-type Vpr (WT) and a mutant Vpr (H71R). 2018 Nucleic acids research Figure HIV H71R 70 74 Vpr;Vpr 43;65 46;68 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. (E, F) 293T cells (2 x 104 cells/well) were co-transfected with pYX014 (E) or pYX017 (100 ng) (F) and either pcDNA3-HA-Vpr WT or pcDNA3-HA-Vpr H71R (100 ng) in triplicate. 2018 Nucleic acids research Figure HIV H71R 143 147 Vpr;Vpr 119;139 122;142 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. 293T cells (2 x 105 cells/well) were cotransfected with 2 mug of pCEP-GFP, pJM105/L1.3 reverse transcriptase-deficient mutant, or pJM101/L1.3 wild-type L1, and 2 mug of pcDNA3-HA, pcDNA3-HA-Vpr WT, pcDNA3-HA-Vpr H71R, or pcDNA3p21. 2018 Nucleic acids research Figure HIV H71R 212 216 RT;Vpr;Vpr 87;190;208 108;193;211 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. 293T cells (2 x 105 cells/well) were transfected with 2 mug of pcDNA3-HA-Vpr WT or pcDNA3-HA-Vpr H71R. 2018 Nucleic acids research Figure HIV H71R 97 101 Vpr;Vpr 73;93 76;96 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Drug dose escalations (mean +- SEM) reflect the differential emergence of resistance to integrase inhibitors by recombinant strains encoding patient-derived integrase with (n = 5) and without (n = 5) the E157Q resistance substitution. 2018 Retrovirology Figure HIV E157Q 204 209 IN;IN 88;157 97;166 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Western blot (right) shows the expression of V5-tagged SIVcol Nef Baits (WT or Y86F) and FLAG-tagged SERINC5 Prey (S5) constructs in HEK293T B0166 cells. 2018 PLoS pathogens Figure HIV Y86F 79 83 Nef 62 65 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. (a) Comparison of pVL between A*24:02+ and A*24:02- in Y135/Y135L-infected or Y135F-infected individuals. 2018 EBioMedicine Figure HIV Y135L;Y135F 60;78 65;83 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. (b) Correlation between the breadth of T cell responses to the 3 epitope peptides and to the NefYF9 epitope and pVL in individuals infected with the Y135F virus was statistically analyzed using Spearman rank test. 2018 EBioMedicine Figure HIV Y135F 149 154 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. (b) Effect of HLA-A*24:02-restricted CD8+ T cells specific for RF10 or RF10-2F on pVL in Y135F-infected individuals. 2018 EBioMedicine Figure HIV Y135F 89 94 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. (c) Comparison of pVL between Y135-infected+Y135L-infected and Y135F-infected HLA-B*35:01-positive individuals. 2018 EBioMedicine Figure HIV Y135F;Y135L 63;44 68;49 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. (d) Comparison of pVL between responders to YF9 and non-responders in Y135/Y135L-infected and Y135F-infected individuals (n = 62). 2018 EBioMedicine Figure HIV Y135L;Y135F 75;94 80;99 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Effect of the T cell responses to 3 HLA-B*35:01-restricted epitopes on pVL in Y135F virus-infected individuals. 2018 EBioMedicine Figure HIV Y135F 78 83 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. The differences in pVL between responders and non-responders to each epitope peptide in individuals infected with Y135F virus were statistically analyzed using the Mann-Whitney test. 2018 EBioMedicine Figure HIV Y135F 114 119 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. The T cell responses to RF10 and RF10-2F epitope peptides were analyzed in Y135F-infected A*24:02+ individuals by ELISPOT assays. 2018 EBioMedicine Figure HIV Y135F 75 80 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (A) Multiple flasks of MT-4 cells were transfected with either P122A or I124A molecular clones (data from two flasks are shown for each mutant, indicated as "1" and "2"). 2018 mBio Figure HIV I124A;P122A 72;63 77;68 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (A) TEM analysis revealed discontinuities (black arrows) in the Gag lattices of I124A virions compared to the WT virions. 2018 mBio Figure HIV I124A 80 85 Gag 64 67 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (D, E) Jurkat cells were transfected with P122A-containing (D) or I124A-containing (E) viral clones. 2018 mBio Figure HIV I124A;P122A 66;42 71;47 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (D) (Upper panels) HeLa cells were transfected with WT, P122A, or I124 molecular clones. 2018 mBio Figure HIV P122A 56 61 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (D) Gag coverage was estimated for 87, 92, 84, and 35 virions for WT, P122A, I124A, and T58S/T107I/P122A samples, respectively. 2018 mBio Figure HIV P122A;T107I;T58S;I124A;P122A 99;93;88;77;70 104;98;92;82;75 Gag 4 7 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (E) Subtomogram averaging of data from the immature Gag lattice demonstrated that the P122A and I124A mutations disrupted the organization of the Gag lattice, whereas the T58S/T107I/P122A revertant regained WT-like Gag lattice organization. 2018 mBio Figure HIV P122A;T107I;T58S;I124A;P122A 182;176;171;96;86 187;181;175;101;91 Gag;Gag;Gag 52;146;215 55;149;218 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (Lower panels) Cryo-ET analysis of WT and I124A virions. 2018 mBio Figure HIV I124A 42 47 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. All revertant mutations were selected in MT-4 cells, except for V11I (*), which arose upon propagation of T58A/P122A in Jurkat cells. 2018 mBio Figure HIV P122A;T58A;V11I 111;106;64 116;110;68 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Compensatory mutations reverse the P122A- and I124A-imposed defects in virus particle production, Gag processing, and infectivity. 2018 mBio Figure HIV I124A;P122A 46;35 51;40 Gag 98 101 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. HeLa cells were transfected with WT or I124A HIV-1 PR- clones. 2018 mBio Figure HIV I124A 39 44 PR 51 53 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. In PR-deficient virions, the P122A and I124A mutations cause defects in the Gag lattice. 2018 mBio Figure HIV I124A;P122A 39;29 44;34 Gag;PR 76;3 79;5 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. No I124A virions containing conical, WT-like cores were observed. 2018 mBio Figure HIV I124A 3 8 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A (in blue) (D) or I124A (in pink) (E) is shown superposed with the CA WT. 2018 mBio Figure HIV I124A;P122A 23;0 28;5 Capsid 72 74 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A and I124 CA mutants assemble into tubes in vitro. 2018 mBio Figure HIV P122A 0 5 Capsid 15 17 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A and I124A mutants acquire compensatory substitutions upon propagation in cell culture. 2018 mBio Figure HIV I124A;P122A 10;0 15;5 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A and I124A mutants exhibit defects in virus replication kinetics, particle infectivity, and virion morphology. 2018 mBio Figure HIV I124A;P122A 10;0 15;5 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A and I124A mutations impair virus particle production and Gag processing. 2018 mBio Figure HIV I124A;P122A 10;0 15;5 Gag 63 66 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. P122A and I124A particles exhibited broader size distributions that peaked at a smaller radius than those of the WT or the revertant (C). 2018 mBio Figure HIV I124A;P122A 10;0 15;5 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Sample loading was adjusted to reflect the decreased particle production of the P122A and I124A mutants (a representative gel is shown on the left; quantitation indicated on the right). 2018 mBio Figure HIV I124A;P122A 90;80 95;85 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Shown are central slices through I124A virions that have a disordered Gag layer (black arrowhead) or are at later stages of maturation, with the protein density, presumably representing processed Gag, distributed throughout the interior of the particles (white arrowhead). 2018 mBio Figure HIV I124A 33 38 Gag;Gag 70;196 73;199 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Small boxes show closeup views of changes induced by (A) P122A (in blue) and (B) I124A (in pink). 2018 mBio Figure HIV I124A;P122A 79;55 86;62 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The Gag layers of the P122A and I124A mutants are seen to be distributed sparsely and discontinuously along the viral envelope compared to the WT or the T58S/T107I/P122A revertant (examples delineated in yellow) (B). 2018 mBio Figure HIV P122A;T107I;T58S;I124A;P122A 164;158;153;32;22 169;163;157;37;27 Env;Gag 118;4 126;7 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The red arrow in panel D highlights repositioning of Q176 in P122A mutant. 2018 mBio Figure HIV P122A 61 66 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Tubular structures were observed for WT CA protein (A) as well as for the P122A (B) and I124A (C) mutants. 2018 mBio Figure HIV I124A;P122A 88;74 93;79 Capsid 40 42 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. V11I was also engineered into the T58A/I124A clone (**). 2018 mBio Figure HIV I124A;T58A;V11I 39;34;0 44;38;4 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. X-ray crystallography demonstrated that P122A and I124A mutations subtly affect the PPIP motif, CypA-binding loop, and CANTD-CACTD intraprotomer interface. 2018 mBio Figure HIV I124A;P122A 50;40 55;45 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Between the two year periods a significant increase of the K103N mutation in males who are not linked to transmission clusters is evident. 2018 PloS one Figure HIV K103N 59 64 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. K103N sequences are grouped according to gender, transmission route, origin and HIV-subtype of the infected person. 2018 PloS one Figure HIV K103N 0 5 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Proportion of not-clusters-linked sequences with K103N mutation according to sub-groups of HIV-infected individuals in 2013/2014 compared to 2015/2016. 2018 PloS one Figure HIV K103N 49 54 HIV infections 91 103 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Three large clusters with M46I, V82L or T215S mutations are shown with blue branches and all sequences carrying the K103N mutation are depicted with dots at the tips. 2018 PloS one Figure HIV K103N;M46I;T215S;V82L 116;26;40;32 121;30;45;36 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Trend line and p-value are indicated for proportions of total K103N. 2018 PloS one Figure HIV K103N 62 67 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Trends for the K103N mutation between 2013 and 2016 in total and in subgroups. 2018 PloS one Figure HIV K103N 15 20 30557314 The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. (A) Schematic representation of wild type Env and truncated CAP256 gp140-FL-IP (soluble CAP256 Env) in which the native signal peptide is replaced with the human tissue plasminogen activator (TPA) sequence, the furin cleavage site with a flexible linker (FL) sequence and an I559P mutation is introduced. 2018 PloS one Figure HIV I559P 275 280 gp140;Env;Env;Capsid;Capsid 67;42;95;60;88 72;45;98;62;90 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. (A) Participant #1 pre-T97A (Mutations - G140S, Q148H; DTG FC 4.61); (B) participant #1 post-T97A (Mutations - G140S, Q148H, T97A; DTG FC 66); (C) participant #2 pre-T97A (Mutations - G140S, Q148H, E138T; DTG FC 6.71); (D) participant #2 post-T97A (Mutations - G140S, Q148H, E138T, T97A; DTG FC 119). 2018 Open forum infectious diseases Figure HIV E138T;E138T;G140S;G140S;G140S;G140S;Q148H;Q148H;Q148H;Q148H;T97A;T97A;T97A;T97A;T97A;T97A 198;275;41;111;184;261;48;118;191;268;23;93;125;166;243;282 203;280;46;116;189;266;53;123;196;273;27;97;129;170;247;286 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Impact of T97A mutation on phenotypic sensitivity to dolutegravir in HIV-1 isolates with baseline partial sensitivity to dolutegravir. 2018 Open forum infectious diseases Figure HIV T97A 10 14 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. (B) Schematic representation of transfer vector for targeting gp150, expressed by the mH5 promoter, into the I8R-G1L locus of wild-type MVA or rMVA GagM. 2019 Journal of virology Figure HIV I8R 109 112 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. The native signal peptide (HIV-1 SP) was replaced with the human tissue plasminogen activator (TPA SP) sequence, the furin cleavage site (KEKR) was replaced with a flexible linker (FL) sequence, and an I559P mutation was introduced. 2019 Journal of virology Figure HIV I559P 202 207 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. (a) Wild-type virus was sensitive to IMC15, while both the V142I Vif point mutant and RAR virus replicated efficiently in the presence of antagonist. 2019 mBio Figure HIV V142I 59 64 Vif 65 68 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Replication profiles of wild-type, V142I Vif, or cloned RN18 analog-resistant (RAR) viruses in the absence or presence of IMC15 antagonist. 2019 mBio Figure HIV V142I 35 40 Vif 41 44 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Vif inhibitor escape was achieved through mutations in Vif (V142I) and the LEF-1 binding site (C9007A nucleotide transversion). 2019 mBio Figure HIV C9007A;V142I 95;60 102;65 Vif;Vif 0;55 3;58 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. (b) Luciferase activity determined in TZM-bl cells exposed to media from HeLa cells transfected with Tat-B*, Tat-B*R57S, Tat-C or Tat-C S57R expression constructs. 2019 Scientific reports Figure HIV R57S;S57R 115;136 119;140 Tat;Tat;Tat;Tat 101;109;121;130 104;112;124;133 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. (c) Induction of cytokine mRNA transcription in C20 microglial cells exposed to media from HeLa cells transfected with Tat-B*, Tat-B* R57S, Tat-C or Tat-C S57R expression constructs. 2019 Scientific reports Figure HIV R57S;S57R 134;155 138;159 Tat;Tat;Tat;Tat 119;127;140;149 122;130;143;152 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. At equivalent inputs, both Tat-B * and Tat-C proteins maximally transactivate only when R57 is present (a) Absorbance values from ELISA assay measuring the relative amounts of Tat protein in media samples from HeLa cells transfected with Tat-B*, Tat-B*R57S, Tat-C or Tat-CS57R expression constructs. 2019 Scientific reports Figure HIV R57S 252 256 Tat;Tat;Tat;Tat;Tat;Tat;Tat 27;39;176;238;246;258;267 30;42;179;241;249;261;270 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Effect of position 57 polymorphism in Tat B or Tat C (R57S vs. 2019 Scientific reports Figure HIV R57S 54 59 Tat;Tat 38;47 41;50 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Note that axons/dendrites in Tat-B* samples and Tat-C S57R are shorter and thinner than the other samples and frequently have beaded appearance (red arrowheads in Tat-B* neurotubulin panel), while Control, Tat-B*-R57S and Tat-C wild type samples display thicker and longer axons/dendrites (white arrowheads in control panel) with fewer beaded processes. 2019 Scientific reports Figure HIV R57S;S57R 213;54 217;58 Tat;Tat;Tat;Tat;Tat 29;48;163;206;222 32;51;166;209;225 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. S57R in Tat-B* or Tat C) on neuroinflammation. 2019 Scientific reports Figure HIV S57R 0 4 Tat;Tat 8;18 11;21 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. The microglia were earlier incubated with spent media from HeLa cells producing Tat-B*, Tat-B*-R57S, Tat-C wild type or Tat-C-S57R. 2019 Scientific reports Figure HIV R57S;S57R 95;126 99;130 Tat;Tat;Tat;Tat 80;88;101;120 83;91;104;123 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. (A) [3H]DA uptake and (B) [3H]WIN 35,428 binding were conducted in PC12 cells transfected with WT hDAT or Y88F/H547A which were incubated with one of the concentrations of ZnCl2 (1, 10, 100 microM, final concentration) or KRH buffer (control) followed by addition of a fixed concentration of [3H]DA uptake or [3H]WIN 35,428 binding. 2019 Scientific reports Figure HIV H547A;Y88F 111;106 116;110 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. (C,D) kinetic analysis of [3H]DA uptake in WT hDAT and Y88F/H547A in the presence or absence of AMPH (1 microM). 2019 Scientific reports Figure HIV H547A;Y88F 60;55 65;59 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. (C) Double mutation D-Y88F/D-H547A on hDAT-TAT structure. 2019 Scientific reports Figure HIV H547A;Y88D;Y88F 29;22;22 34;28;28 Tat 43 46 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. (D) Triple mutation D-Y88F/D-K92M/D-H547A on hDAT-TAT structure. 2019 Scientific reports Figure HIV H547A;K92D;K92M;Y88D;Y88F 36;29;29;22;22 41;35;35;28;28 Tat 50 53 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Addition of a triple mutation of D-Y88F, D-K92M, and D-H547A, also eliminates the hydrogen bond with T-P18. 2019 Scientific reports Figure HIV H547A;K92M;Y88F 55;43;35 60;47;39 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. D-H547A mutation eliminates one hydrogen bond with T-R49, and D-Y88F mutation eliminates the hydrogen bond with T-K19. 2019 Scientific reports Figure HIV H547A;Y88F 2;64 7;68 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Each fractional efflux value of [3H]DA in WT hDAT and Y88F/H547A was expressed as percentage of total [3H]DA in the cells at the start of the experiment. 2019 Scientific reports Figure HIV H547A;Y88F 59;54 64;58 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Effects of PMA on basal PKC-regulated DAT function in WT hDAT and Y88F/H547A mutant. 2019 Scientific reports Figure HIV H547A;Y88F 71;66 76;70 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Effects of Y88F/H547A and Y88F/K92M/H547A on [3H]DA uptake and [3H]WIN35,428 binding. 2019 Scientific reports Figure HIV H547A;K92M;Y88F;H547A;Y88F 36;31;26;16;11 41;35;30;21;15 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Effects of Y88F/H547A mutant on transporter conformational transitions. 2019 Scientific reports Figure HIV H547A;Y88F 16;11 21;15 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Fractional efflux values of [3H]DA at 1, 10, 20, 30 and 40 min are expressed as the percentage of total [3H]DA with preloading with 0.05 muM (WT hDAT: 11044 +- 241 dpm and Y88F/H547A: 660 +- 123 dpm) present in the cells at the start of the experiment (n = 5/group). 2019 Scientific reports Figure HIV H547A;Y88F 177;172 182;176 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Functional DA efflux was conducted in PC12 cells transfected WT hDAT or Y88F/H547A by preloading with a fixed concentration of [3H]DA (0.05 muM, final concentration) at room temperature for 20 min followed by replacing with fresh buffer at indicated time points. 2019 Scientific reports Figure HIV H547A;Y88F 77;72 82;76 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. of specific [3H]DA uptake relative to respective controls as 100% for individual experiment (WT hDAT: 1109.30 +- 230.27 dpm and Y88F/H547A: 400.13 +- 81.75 dpm and n = 5/group). 2019 Scientific reports Figure HIV H547A;Y88F 133;128 138;132 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. PC12 cells transfected with WT hDAT or Y88F/H547A were preincubated with vehicle or recombinant Tat1-86 (rTat1-86) at room temperature for 20 min followed by [3H]DA application. 2019 Scientific reports Figure HIV H547A;Y88F 44;39 49;43 Tat 96 99 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. K103N and M184V drug resistance mutations by time point as detected by Illumina sequencing. 2019 Open forum infectious diseases Figure HIV M184V;K103N 10;0 15;5 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Level of K103N and M184V drug resistance mutations for each participant at early suppression (1), midpoint suppression (2), and latest suppression (3) detected through Illumina sequencing at a threshold of 2%. 2019 Open forum infectious diseases Figure HIV K103N;M184V 9;19 14;24 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Time points at which K103N or M184V were also detected by Sanger sequencing are indicated by plus signs (+). 2019 Open forum infectious diseases Figure HIV K103N;M184V 21;30 26;35 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. The asterisk indicates polymorphic mutations occurring at <20% in the integrase gene [E96D, I203M, N254K and V260I (16.6%), A265V, D232N, D270H, G106A/K, K219N, R269K and V165I (11.1%), A23V, D116N, D229E, D253H, D279N, E85K, E157K, E170K, E198D/E, E212L, F181L, G70R, G82E, G136R, G149R, G247E, I60M, I200L, I220L, I268I/L, K14R, K111T, K173R, K186R, K188R, K236Q, K240E, M154I, P238G, Q221S/T, R107K, R166K, R224Q, S195T, S283G, V31I, V110I and Y227F (5.5%)]. 2019 The Journal of antimicrobial chemotherapy Figure HIV A23V;A265V;D116N;D229E;D232N;D253H;D270H;D279N;E157K;E170K;E198D;E198E;E212L;E85K;E96D;F181L;G106A;G106K;G136R;G149R;G247E;G70R;G82E;I200L;I203M;I220L;I268I;I268L;I60M;K111T;K14R;K173R;K186R;K188R;K219N;K236Q;K240E;M154I;N254K;P238G;Q221S;Q221T;R107K;R166K;R224Q;R269K;S195T;S283G;V110I;V165I;V260I;V31I;Y227F 186;124;192;199;131;206;138;213;226;233;240;240;249;220;86;256;145;145;275;282;289;263;269;302;92;309;316;316;296;331;325;338;345;352;154;359;366;373;99;380;387;387;396;403;410;161;417;424;437;171;109;431;447 190;129;197;204;136;211;143;218;231;238;247;247;254;224;90;261;152;152;280;287;294;267;273;307;97;314;323;323;300;336;329;343;350;357;159;364;371;378;104;385;394;394;401;408;415;166;422;429;442;176;114;435;452 IN 70 79 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. HuT-R5 cells were infected with replication-competent WT HIV-1 or HIV-1 with the mutation M230I in the RT. 2019 Journal of virology Figure HIV M230I 90 95 RT 103 105 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. HuT-R5 cells were infected with WT HIV-1 and G112D HIV-1 (A), WT HIV-1 and M230I HIV-1 (B), WT HIV-1 and G112D/M230I HIV-1 (double mutant [DM]) (C), G112D HIV-1 and G112D/M230I HIV-1 (DM) (D), or M230I HIV-1 and G112D/M230I HIV-1 (DM) (E). 2019 Journal of virology Figure HIV G112D;G112D;G112D;G112D;G112D;M230I;M230I;M230I;M230I;M230I 45;105;149;165;212;75;111;171;196;218 50;110;154;170;217;80;116;176;201;223 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The mutated G112D and M230I are modeled into the structure and are shown in magenta and circled red. 2019 Journal of virology Figure HIV G112D;M230I 12;22 17;27 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. a Analysis of the extent of HIV-1 infection of the indicated cell lines by the A92E CA mutant in the presence and absence of CsA. 2019 Retrovirology Figure HIV A92E 79 83 Capsid 84 86 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. a Schematic diagram of the TIRF microscopy binding assay using cross-linked CA tubes assembled inside the flow cell from CA A14C/E45C and CA K158C-AF488 (20:1, mol/mol) and immobilized on the surface via an antibody. 2019 Retrovirology Figure HIV A14C;E45C;K158C 124;129;141 128;133;146 Capsid;Capsid;Capsid 76;121;138 78;123;140 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. b Representative equilibrium binding curves obtained for wild type (top) and A25D (bottom) by plotting the mean number of CypA molecules bound per capsid at equilibrium as a function of CypA concentration. 2019 Retrovirology Figure HIV A25D 77 81 Capsid 147 153 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. c KD (top graph) and mean number of CypA molecules bound per capsid at saturation (corresponding to the number of CypA loops that can be occupied simultaneously) (bottom graph) for the interaction of wild type CypA and CypA A25D with the capsid determined in independent experiments using different virus preparations; each symbol represents an independent experiment. 2019 Retrovirology Figure HIV A25D 224 228 Capsid;Capsid 61;238 67;244 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. CypA A25D binds with the same affinity as wild-type CypA to authentic HIV-1 capsids. 2019 Retrovirology Figure HIV A25D 5 9 Capsid 76 83 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. d The KD values were estimated to be 14.5 +- 5 muM (WT), 17.2 +- 4.8 muM (A25D), 17.7 +- 6.7 muM (K27D), 16.4 +- 3.8 muM (P29K) and 17 +- 9.2 muM (K30D) (mean +- SD, n >= 6). 2019 Retrovirology Figure HIV A25D;K27D;K30D;P29K 74;98;147;122 78;102;151;126 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. e Maximum binding ratios of CypA binding with CA tubes (molar ratio of CypA:CA when saturated) were estimated at 0.40 +- 0.11 (WT), 0.39 +- 0.08 (A25D), 0.24 +- 0.13 (K27D), 0.32 +- 0.10 (P29K) and 0.39 +- 0.20 (K30D) (mean +- SD, n >= 6). 2019 Retrovirology Figure HIV A25D;K27D;K30D;P29K 146;167;212;188 150;171;216;192 Capsid;Capsid 46;76 48;78 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Equilibrium analysis of surface plasmon resonance (SPR) curves of CypA binding on surfaces modified with CA K158C (reacted with a maleimide derivative of biotin) or cross-linked CA A14C/E45C/W184A/M185A hexamers (reacted with an NHS ester derivative of biotin). 2019 Retrovirology Figure HIV A14C;E45C;M185A;W184A;K158C 181;186;197;191;108 185;190;202;196;113 Capsid;Capsid 105;178 107;180 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. The fit of an equilibrium binding model (black line) gave estimates for KD and number of molecules bound at saturation; wild type: KD = 11.6 muM, number of molecules = 1381; A25D: KD = 11.2 muM, number of molecules = 688. 2019 Retrovirology Figure HIV A25D 174 178 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. a, FRET histogram of HIV-1BG505(T332N). 2019 Nature Figure HIV T332N 32 37 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. a, SOS and/or I559P (IP) changes introduced into native HIV-1BG505 Q23 Env do not influence Env processing or virus incorporation. 2019 Nature Figure HIV I559P 14 19 Env;Env 71;92 74;95 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. b, c, Neutralization of HIV-1JR-FL wild type, 100%-peptide-tagged V1-Q3 V4-A1, 100%-amber-suppressed V1-Asn136TAG V4-A1 and V4-A1 alpha6-Arg542TAG by sCD4D1D2-Igalphatp (b), and eCD4-Ig(Q40A, mim2) (c). 2019 Nature Figure HIV Q40A;N136A;N136G;N136T 186;104;104;104 190;113;113;113 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. b, The structure-stabilizing modifications A501C and T605C (SOS) and I559P used in the design of BG505 sgp140 SOSIP.664 abort HIV-1 infectivity. 2019 Nature Figure HIV A501C;I559P;T605C 43;69;53 48;74;58 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Env expression, processing and virus incorporation for HIV-1BG505 Q23 carrying SOS, I559P and SOS and I559P (SOS&IP) changes were tested by centrifugation of viruses from cell culture supernatants, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of dithiothreitol, and western blotting using the antiserum to HIV-1 gp120 (NIH AIDS reagent no. 2019 Nature Figure HIV I559P;I559P 84;102 89;107 gp120;Env 353;0 358;3 AIDS 364 368 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. f, The FRET histogram of HIV-1BG505 that carries the T332N substitution in Env is overlaid with that of wild-type HIV-1BG505. 2019 Nature Figure HIV T332N 53 58 Env 75 78 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. HIV-1 JR-FL V1-Asn136TAG V4-A1 carries a TAG at position Asn136 in V1 and the A1 peptide in V4. 2019 Nature Figure HIV N136A;N136G;N136T 15;15;15 24;24;24 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. i-l, Experiment as in c-f, characterizing the conformational landscape upon binding of PGT151 to click-labelled HIV-1JR-FL V1-Asn136TAG V4-A1 (i, k), and HIV-1BG505 V1-Q3 V4-Ser401TAG (j, l). 2019 Nature Figure HIV N136A;N136G;N136T 126;126;126 135;135;135 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Infectivity of HIV-1BG505 Q23 SOS and I559P was measured by a Gaussia Luciferase assay, and normalized to that of wild-type HIV-1BG505 Q23. 2019 Nature Figure HIV I559P 38 43 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. SOS and I559P effects on infectivity and conformational plasticity of sgp140 SOSIP.664. 2019 Nature Figure HIV I559P 8 13 30971821 Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. The T332N substitution in HIV-1BG505 Env does not detectably change the conformation of the Env. 2019 Nature Figure HIV T332N 4 9 Env;Env 37;92 40;95 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Electrophoretic analysis of the strand transfer reaction products for IN_CRF (lane 2) and its mutants G118R/ E138K (lane 3) and Q148K/G140S (lane 4) (reaction time 300 min). 2019 Acta naturae Figure HIV E138K;G118R;G140S;Q148K;E138K;G118R;G140S;Q148K 110;103;135;129;109;102;134;128 115;108;140;134;114;107;139;133 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Lane 1 - IN_CRF; lane 2 - IN_A; lane 3 - IN_CRF (G118R/E138K); lane 4 - IN_CRF (Q148K/G140S); MW - molecular weight marker . 2019 Acta naturae Figure HIV E138K;G118R;G140S;Q148K 55;49;86;80 60;54;91;85 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. Lane 1 - IN_CRF; lane 2 - IN_A; lane 3 - IN_CRF (G118R/E138K); lane 4 - IN_CRF (Q148K/G140S); MW - molecular weight marker. 2019 Acta naturae Figure HIV E138K;G118R;G140S;Q148K 55;49;86;80 60;54;91;85 31024744 Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1. SDS-PAGE analysis of purified consensus IN_CRF and its mutant forms G118R/E138K and Q148K/ G140S. 2019 Acta naturae Figure HIV E138K;G118R;G140S;Q148K;E138K;G118R;G140S;Q148K 75;69;92;85;74;68;91;84 80;74;97;90;79;73;96;89 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. (A) Curling of the flap due to flap mutations M46L, G48V, and I54V observed in inhibitor-free structures of PRS17-D25N (green ribbon) and PRS17 (orange ribbon) in comparison to PR (gray ribbon). 2019 ACS omega Figure HIV G48V;I54V;M46L;D25N 52;62;46;114 56;66;50;118 PR;PR;PR 108;138;177 110;140;179 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. (B) Flipped peptide bond between Ile50 and Gly51 of PRS17-D25N (green carbon) and PRS17 (orange carbon). 2019 ACS omega Figure HIV D25N 58 62 PR;PR 52;82 54;84 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. (E) Interactions of major conformation P3 Arg (salmon carbon) and minor conformation P4' Nle (magenta carbon) of V82A single mutant complex PRV82A/CA-p2 in comparison to PRS17/CA-p2 (green carbon). 2019 ACS omega Figure HIV V82A 113 117 Capsid;Capsid;PR;PR 147;176;140;170 149;178;142;172 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Altered flap of PRS17-D25N. 2019 ACS omega Figure HIV D25N 22 26 PR 16 18 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The circled portions of the flap are magnified in sticks for inhibitor-free PRS17-D25N (green carbon), PRS17 (orange carbon), and PR (gray carbon). 2019 ACS omega Figure HIV D25N 82 86 PR;PR;PR 76;103;130 78;105;132 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The critical G48V and V82S mutations involved in substrate analogue binding are shown as red spheres in each subunit. 2019 ACS omega Figure HIV G48V;V82S 13;22 17;26 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The van der Waals contacts of P3 Arg of PRV82A/CA-p2 are shown in black, while those of P4' Nle are shown in magenta. 2019 ACS omega Figure HIV V82A 42 46 Capsid;PR 47;40 49;42 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. A ribbon representation of the wild type C-SA HIV protease (A) from a crystal structure (3U71) in its homodimeric form and E35D G S variant (B). 2019 Journal of enzyme inhibition and medicinal chemistry Figure HIV E35D 123 127 PR 50 58 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Gibbs free binding free energy of the E35D G S protease and the wild type C-SA HIV protease. 2019 Journal of enzyme inhibition and medicinal chemistry Figure HIV E35D 38 42 PR;PR 47;83 55;91 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Log vitality values for the E35D G S mutant protease with respect to the nine inhibitors using wild type as a reference. 2019 Journal of enzyme inhibition and medicinal chemistry Figure HIV E35D 28 32 PR 44 52 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The mutation (E35D) is in red and the insertions are shown in blue. 2019 Journal of enzyme inhibition and medicinal chemistry Figure HIV E35D 14 18 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The wild type (C-SA) is shown in green, and mutant (E35D G S) in blue. 2019 Journal of enzyme inhibition and medicinal chemistry Figure HIV E35D 52 57 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The wild type is represented in blue whilst the E35D G S is in red. 2019 Journal of enzyme inhibition and medicinal chemistry Figure HIV E35D 48 52 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. (C) A structural model of a hexameric CA mutant of the RGDA/Q112D virus. 2019 Journal of virology Figure HIV Q112D 60 65 Capsid 38 40 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. A cyclophilin A binding-deficient capsid mutant, the RGDA/Q112D virus, is hypersensitive to IFN-beta in T cells. 2019 Journal of virology Figure HIV Q112D 58 63 Capsid 34 40 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Adaptation of the RGDA/Q112D virus in IFN-beta-treated Jurkat cells. 2019 Journal of virology Figure HIV Q112D 23 28 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. An IFN-hypersensitive CA mutant RGDA/Q112D virus (red) evolved to be IFN resistant by acquiring additional Q4R or G94D/G116R mutations. 2019 Journal of virology Figure HIV G116R;G94D;Q112D;Q4R 119;114;37;107 124;118;42;110 Capsid 22 24 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Another IFN-resistant virus, the RGDA/Q112D+G94D/G116R virus (green), accelerates the kinetics of reverse transcription to a smaller degree only in the presence of IFN. 2019 Journal of virology Figure HIV G116R;G94D;Q112D 49;44;38 54;48;43 RT 98 119 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. CA mutations in the adapted viruses confer IFN-beta resistance on the RGDA/Q112D virus. 2019 Journal of virology Figure HIV Q112D 75 80 Capsid 0 2 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Cells were infected with 100 ng (p24) of the NL-VifS virus encoding the RGDA/Q112D mutations. 2019 Journal of virology Figure HIV Q112D 77 82 p24;Vif 33;48 36;51 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Limited contributions of CPSF6 and CypA to the IFN-beta resistance of the RGDA/Q112D virus harboring the Q4R mutation or the G94D/G116R mutations. 2019 Journal of virology Figure HIV G116R;G94D;Q112D;Q4R 130;125;79;105 135;129;84;108 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Steps at or before the second-strand transfer of reverse transcription of the RGDA/Q112D virus were suppressed by IFN-beta. 2019 Journal of virology Figure HIV Q112D 83 88 RT 49 70 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The G94/G116R mutation confers IFN-beta resistance to the WT virus. 2019 Journal of virology Figure HIV G116R 8 13 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The G94D/G116R mutations could generate intramolecule salt bridges of R116 with the D94 residue. 2019 Journal of virology Figure HIV G116R;G94D 9;4 14;8 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The IFN-resistant RGDA/Q112D+Q4R virus (blue) shows accelerated kinetics of reverse transcription (RT) and a faster initiation of uncoating in both the presence and the absence of IFN. 2019 Journal of virology Figure HIV Q112D;Q4R 23;29 28;32 RT;RT 76;99 97;101 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation accelerates the kinetics of reverse transcription of the RGDA/Q112D virus. 2019 Journal of virology Figure HIV Q112D;Q4R 79;4 84;7 RT 45 66 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation sensitizes the RGDA/Q112D virus to MxB restriction despite conferring IFN-beta resistance. 2019 Journal of virology Figure HIV Q112D;Q4R 37;4 42;7 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D virus obtained IFN-beta resistance with the G94D mutation and then obtained the G116R mutation to compensate for the impaired infectivity. 2019 Journal of virology Figure HIV G116R;G94D;Q112D 95;59;9 100;63;14 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The virus showed a degree of interaction with MxB similar to that of the RGDA/Q112D virus and a weaker interaction with CPSF6 than the RGDA/Q112D virus. 2019 Journal of virology Figure HIV Q112D;Q112D 78;140 83;145 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Cryo-EM structural details for reconstructions of CH235UCA complex with HIV-1 Env trimer CH505TF.N279K.G458Y.SOSIP.664. 2019 PLoS pathogens Figure HIV G458Y;N279K 103;97 108;102 Env 78 81 31551948 Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence. Mutations Q148R, Q148H, G140S, N155H, and T97A are all contained in this cluster. 2019 Frontiers in microbiology Figure HIV G140S;N155H;Q148H;Q148R;T97A 24;31;17;10;42 29;36;22;15;46 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Crystal structures of PIE12/IQN17 (Q577R) (PDB: 6PSA) and PIE12/IQN17 (WT PDB:3L37). 2019 Retrovirology Figure HIV Q577R 35 40 PI;PI 22;58 24;60 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Protein interaction analysis of Q577R mutation. 2019 Retrovirology Figure HIV Q577R 32 37 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. SPR equilibrium binding data (in triplicate) for interaction between immobilized IZN36 (WT or Q577R) and PIE12 monomer. 2019 Retrovirology Figure HIV Q577R 94 99 PI 105 107 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Stereoview of the overlay of crystal structures of PIE12 binding to the WT (yellow) and a mutant (Q577R, turquoise) pocket showing the disruption of hydrogen bonding interactions mediated by Q577. 2019 Retrovirology Figure HIV Q577R 98 103 PI 51 53 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The calculated KD values are 0.031 microM for WT and 2.0 microM for Q577R. 2019 Retrovirology Figure HIV Q577R 68 73 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The primary resistance mutations (Q577R/N/K) are represented in red, and candidate resistance and fitness compensation mutations are shown in black. 2019 Retrovirology Figure HIV Q577K;Q577N;Q577R 34;34;34 43;43;43 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Estimated probability of remaining free from virological failure (VF) with (blue) and without (red) the presence of the M184V/I mutation in (A) the overall population (P = .295) and in the subgroup population (at least 1 VF before the switch to ABC/3TC/DTG), (B) before (P = .781) and (C) after (e = 0.733) inverse probability weighted adjustment. 2019 Open forum infectious diseases Figure HIV M184I;M184V 120;120 127;127 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Kaplan Meier plots showing probability of remaining free from virological failure (VF) or virological blips with (blue) and without (red) the presence of the M184V/I mutation in (A) the overall population (P = .022) and in the subgroup population (at least 1 VF before the switch to ABC/3TC/DTG), (B) before (P = .106) and (C) after (P = .160) inverse probability weighted analysis adjustment. 2019 Open forum infectious diseases Figure HIV M184I;M184V 158;158 165;165 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. (A) Western blot analysis of the input expression of the different over-expressed C-terminal EGFP-tagged Nef constructs (wt or mutants: Nef-G2A or Nef-PPAA), cells expressing HA-wt-HDAC6 or HA-wt-PI4P5-K Ialpha (these two constructs are for tag and specificity of binding controls), free EGFP (pEGFP-C1 expressing cells for EGFP control) or co-expressing HA-wt-HDAC6 with wt-Nef-EGFP, Nef-G2A-EGFP, or Nef-PPAA-EGFP constructs. 2019 Frontiers in microbiology Figure HIV G2A;G2A 140;389 143;392 Nef;Nef;Nef;Nef;Nef;Nef 105;136;147;375;385;402 108;139;150;378;388;405 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. All experiments were performed in HEK-293T cells, transfected with 1 mug of HA-wt-HDAC6 and 0.5 mug of each assayed C-terminal EGFP-tagged Nef mutant: Nef-G2A, Nef-EA, Nef-PPAA, and Nef-LLAA. 2019 Frontiers in microbiology Figure HIV G2A 155 158 Nef;Nef;Nef;Nef;Nef 139;151;160;168;182 142;154;163;171;185 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Biochemical immunoprecipitation analysis of the interaction of Nef-G2A and Nef-PPAA Nef mutants with HDAC6 in HEK-293T cells. 2019 Frontiers in microbiology Figure HIV G2A 67 70 Nef;Nef;Nef 63;75;84 66;78;87 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. The antiviral HDAC6 functions are only neutralized by functional full-length Nef and Nef mutants able to target HDAC6, such Nef-G2A and Nef-EA. 2019 Frontiers in microbiology Figure HIV G2A 128 131 Nef;Nef;Nef;Nef 77;85;124;136 80;88;127;139 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. The effect of Nef-G2A and Nef-PPAA mutants, expressed alone (lanes 7 and 9, respectively) or together with HDAC6 (lanes 6 and 8, respectively) on Pr55Gag and Vif stability are similarly shown. 2019 Frontiers in microbiology Figure HIV G2A 18 21 Nef;Nef;Vif;PR 14;26;158;146 17;29;161;148 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. For SDRMs T215S; T215S + L210W; K101E; M41L + T215L; V32I + I47V + T215D/E + K103N + L100I (TRIPLE_CLASS_RES) that form local transmission clusters (TCs), above each cluster corresponding SDRMs were noted, meaning that all sequences inside TCs harbour SDRMs. 2019 Scientific reports Figure HIV I47V;K101E;K103N;L100I;L210W;M41L;T215D;T215E;T215L;T215S;T215S;V32I 60;32;77;85;25;39;67;67;46;10;17;53 64;37;82;90;30;43;74;74;51;15;22;57 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Association of M184V/I mutation with log10 viral load across subgroups. 2020 The Journal of infectious diseases Figure HIV M184I;M184V 15;15 22;22 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Differences in CD4 count during virological failure within studies by presence and absence of M184V/I. 2020 The Journal of infectious diseases Figure HIV M184I;M184V 94;94 101;101 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Estimates to the left of center line indicate lower CD4 count in participants with M184V/I. 2020 The Journal of infectious diseases Figure HIV M184I;M184V 83;83 90;90 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Estimates to the right indicate higher viral load in the presence of M184V/I, and estimates to the left indicate lower viral load in presence of M184V/I. 2020 The Journal of infectious diseases Figure HIV M184I;M184I;M184V;M184V 69;145;69;145 76;152;76;152 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Estimates to the right indicate higher viral load in the presence of M184V/I. 2020 The Journal of infectious diseases Figure HIV M184I;M184V 69;69 76;76 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Human immunodeficiency virus reverse-transcriptase inhibitor resistance-associated mutations enriched in virologically failing participants (n = 1445) with M184V/I. 2020 The Journal of infectious diseases Figure HIV M184I;M184V 156;156 163;163 RT 29 50 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. In vitro replication measurement of lamivudine-resistant subtype C clinical isolate containing M184V and L74I and revertant mutations. 2020 The Journal of infectious diseases Figure HIV L74I;M184V 105;95 109;100 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Mutations are shown that occurred in at least 10% of individuals with M184V/ at a significance level of <.001. 2020 The Journal of infectious diseases Figure HIV M184V 70 75 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. b The mutation E560K changed into the positively charged residue and has longer side chain than wild type, and it still interacts with Q650 with shorter distance between them (2.37 A), or probably it forms two hydrogen bonds with nitrogen atom of Q650. 2019 Retrovirology Figure HIV E560K 15 20 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. c E560D mutation has only shorter side chain than wild type and may interrupt the hydrogen bond with the longer distance (3.91 A) between E560D and Q650. 2019 Retrovirology Figure HIV E560D;E560D 2;138 7;143 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. d E560G mutation removes the interaction between E560 and Q650. 2019 Retrovirology Figure HIV E560G 2 7 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Inhibition of pseudoviruses bearing Envs with E560K/D/G mutations by broad neutralizing antibodies, 2F5 and 4E10. 2019 Retrovirology Figure HIV E560D;E560G;E560K 46;46;46 55;55;55 Env 36 40 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Peptide and sCD4 inhibition of pseudovirus bearing Envs with E560K/D/G mutations. 2019 Retrovirology Figure HIV E560D;E560G;E560K 61;61;61 70;70;70 Env 51 55 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The bands of 6HB formed by C34 and N36 E560K or E560G migrated upward due to reduced negative charges of 6HB. 2019 Retrovirology Figure HIV E560G 48 53 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The wild-type E560 and mutations E560K/D/G are modeled in the 6HB conformation (PDB code: 1AIK) in a ribbon model in longitudinal view. 2019 Retrovirology Figure HIV E560D;E560G;E560K 33;33;33 42;42;42 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. (b) Only clusters with putative sequence pairs sharing DRMs at >=2% threshold are shown; shared K103N is identified. 2020 The Journal of antimicrobial chemotherapy Figure HIV K103N 96 101 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Sequences sharing K103N are shown. 2020 The Journal of antimicrobial chemotherapy Figure HIV K103N 18 23 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. a A pre-incubated solution of 120 nM M184V and 30 nM 5'-[32P]-labeled 18/26-mer was mixed with increasing concentrations of (-)-FTC-TP (3.75 microM, ; 7.5 microM, ; 15 microM, ; 30 microM, x; 60 microM, ; 120 microM, ; 240 microM, ; 480 microM, ) for various times at 37 C before being quenched with 0.37 M EDTA. 2019 Communications biology Figure HIV M184V 37 42 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. a Alignment of the RT-DNA (PDB code 3KJV, cyan) and M184V-DNA (PDB code 6UKO, magenta) binary complexes. 2019 Communications biology Figure HIV M184V 52 57 RT 19 21 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. b Overlay of the ternary structures of RT-DNA dCTP and M184V-DNA dCTP. 2019 Communications biology Figure HIV M184V 55 60 RT 39 41 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. c Alternate view of (-)-FTC-TP binding conformation with WT and M184V structures. 2019 Communications biology Figure HIV M184V 64 69 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. dCTP is positioned for incorporation (productive binding conformation) whether bound to WT RT or M184V. 2019 Communications biology Figure HIV M184V 97 102 RT 91 93 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Determination of kinetic parameters for (-)-FTC-TP incorporation onto 18/26-mer dsDNA catalyzed by the M184V mutant of HIV-1 RT. 2019 Communications biology Figure HIV M184V 103 108 RT 125 127 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Omit 2Fo-Fc electron maps (blue mesh) for ternary complexes of WT and M184V HIV-1 RT. 2019 Communications biology Figure HIV M184V 70 75 RT 82 84 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Structures of M184V HIV-1 RT-DNA binary and ternary complex with dCTP. 2019 Communications biology Figure HIV M184V 14 19 RT 26 28 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Ternary complexes of WT and M184V HIV-1 RT showing 2Fo - Fc omit electron density maps (blue mesh) of (a) RT-DNA (-)-FTC-TP (PDB code 6UJX), (b) RT-DNA (-)-3TC-TP (PDB code 6UJY), (c) RT-DNA (+)-FTC-TP (PDB code 6UJZ), (d) RT-DNA dCTP (PDB code 6UIT), (e) M184V-DNA (-)-FTC-TP (PDB code 6UIR), and (f) M184V-DNA dCTP (PDB code 6UIS). 2019 Communications biology Figure HIV M184V;M184V;M184V 28;254;300 33;261;307 RT;RT;RT;RT;RT 40;106;145;184;223 42;108;147;186;225 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Ternary crystal structure of M184V-DNA bound to (-)-FTC-TP. 2019 Communications biology Figure HIV M184V 29 34 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The M184V mutation is positioned in the P-site (priming site) directly below the primer 3'-terminal nucleotide. 2019 Communications biology Figure HIV M184V 4 9 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. There is no steric clash between M184V and dCTP. 2019 Communications biology Figure HIV M184V 33 38 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Associations between individual, viral and antiretroviral (ART) characteristics and detection of any new major drug resistance mutation (DRM) following ART switch subsequent to detection of the M184V/I mutation, with overall effect estimate for lamivudine (3TC) or emtricitabine (FTC) use. 2020 HIV medicine Figure HIV M184I;M184V 194;194 201;201 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Associations between individual, viral and antiretroviral (ART) characteristics and viral suppression to < 200 copies/mL following ART switch subsequent to detection of the M184V/I mutation. 2020 HIV medicine Figure HIV M184I;M184V 173;173 180;180 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Associations between individual, viral and antiretroviral therapy (ART) characteristics and incidence rate of new viral major drug resistance mutations (DRMs) following ART switch subsequent to detection of the M184V/I mutation, with overall effect estimate for lamivudine (3TC) or emtricitabine (FTC). 2020 HIV medicine Figure HIV M184I;M184V 211;211 218;218 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. (A) A structural model of a hexameric CA mutant of the RGDA/Q112D virus, highlighting the positions of the 4th and 112th residues. 2020 AIDS research and human retroviruses Figure HIV Q112D 60 65 Capsid 38 40 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. A CA mutant protein harboring both the Q4R and Q112D substitutions is predicted to generate intermolecular salt bridges between the R4 and D112 residues of adjacent monomers. 2020 AIDS research and human retroviruses Figure HIV Q112D;Q4R 47;39 52;42 Capsid 2 4 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Opposite effects of the Q4R substitution on CA-CPSF6 interaction between RGDA/Q112D and WT viruses. 2020 AIDS research and human retroviruses Figure HIV Q112D;Q4R 78;24 83;27 Capsid 44 46 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Requirement for the combination of the Q4R and Q112E substitutions in CA for normal levels of CA-CPSF6 interaction of the SIVcpzMT145 virus. 2020 AIDS research and human retroviruses Figure HIV Q112E;Q4R 47;39 52;42 Capsid;Capsid 70;94 72;96 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. (A) Inhibitory phenotype of 148.1-38m against P420A can be partially rescued with high aptamer concentration (160 and 180 nM). 2020 Nucleic acids research Figure HIV P420A 46 51 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. (B) R277K was used as a control and stayed fully resistant to 70.05core2 under any tested concentration. 2020 Nucleic acids research Figure HIV R277K 2 9 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Among tested mutants, P420A, L422A and K424A had reduced susceptibility to 148.1-38m inhibition. 2020 Nucleic acids research Figure HIV K424A;L422A;P420A 39;29;22 44;34;27 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. In contrast, 70.05core2 inhibits all mutants except for R277K. 2020 Nucleic acids research Figure HIV R277K 56 61 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Inhibition profiles of R277K and T419A are similar to WT HXB2. 2020 Nucleic acids research Figure HIV R277K;T419A 23;33 28;38 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. R277K is fully resistant to 70.05core2 and was used as control for the assay. 2020 Nucleic acids research Figure HIV R277K 0 5 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Significant difference between inhibition of 148.1-38m against HXB2 and P420A mutant is represented in the graph. 2020 Nucleic acids research Figure HIV P420A 72 77 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. T419A and P420A behaved similarly to WT HXB2 in the presence of 70.05core2 indicating that change in susceptibility observed with P420A is specific only to 148.1-38m. 2020 Nucleic acids research Figure HIV P420A;P420A;T419A 10;130;0 15;135;5 32004936 Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Binding modes of 10i into the NNBS of (a) HIV-1 Y181C RT (PDB code: 1JLB); (b) HIV-1 K103N/Y181C RT (PDB code: 5VQY); (c) HIV-1 L100I/K103N RT (PDB code: 2ZE2). 2020 European journal of medicinal chemistry Figure HIV K103N;Y181C;K103N;L100I 134;91;85;128 139;96;90;133 RT;RT;RT 54;97;140 56;99;142 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. 302335, 301844, 301770, and 301635 were four patients infected with CRF01_AE, in whom both the S68G and K65R mutations were detected after treatment failure. 2020 BMC infectious diseases Figure HIV K65R;S68G 104;95 108;99 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Black columns and white columns represent the K65R/S68G double mutation and K65R mutation pseudoviruses with mutant pol gene sequences obtained from patients, respectively. 2020 BMC infectious diseases Figure HIV K65R;K65R;S68G 46;76;51 50;80;55 Pol 116 119 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Growth competition assay for the K65R and K65R/S68G infectious clones. 2020 BMC infectious diseases Figure HIV K65R;K65R;S68G 33;42;47 37;46;51 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. K65R/S68G: 4:6 (a), 1:1 (b), and 9:1 (c). 2020 BMC infectious diseases Figure HIV S68G;K65R 5;0 9;4 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Temporal association of S68G and K65R mutations in individuals infected with CRF01_AE during antiretroviral treatment. 2020 BMC infectious diseases Figure HIV K65R;S68G 33;24 37;28 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The black circle and triangle represent the percentages of K65R and S68G quasispecies, respectively. 2020 BMC infectious diseases Figure HIV K65R;S68G 59;68 63;72 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The infectious clones of K65R and K65R/S68G obtained from patients were co-cultured for 13 days in PBMCs with the following input ratios for K65R vs. 2020 BMC infectious diseases Figure HIV K65R;K65R;K65R;S68G 25;34;141;39 29;38;145;43 32048186 Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV-1. a The antiviral effects of 1-6 on pNL4-3gp41(36G)V38E,N42S in C8166 cells were assessed by syncytium formation. 2020 Natural products and bioprospecting Figure HIV N42S;V38E 54;48 58;53 32048186 Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV-1. b The antiviral effects of 1-6 on pNL4-3gp41(36G)V38A,N42T in C8166 cells were assessed by syncytium formation. 2020 Natural products and bioprospecting Figure HIV N42T;V38A 54;48 58;53 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. (a) Superimposition of 3TC-TP in RT3MB, ETV-TP in RT3MB, and modeled 3TC moiety of 3TC-TP in RT3MB/F160M/M184V representing the deviation by ~1 A of 3TC moiety in RT3MB/F160M/M184V, as indicated by red arrow. 2020 Scientific reports Figure HIV F160M;F160M;M184V;M184V 99;169;105;175 104;174;110;180 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. (b) Superimposition of all of the Met/Val184 side-chains analyzed in this study. 2020 Scientific reports Figure HIV M184V 34 44 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. (c) Stereo-view structure of Val184 and nearby residues in the RT3MB/F160M/M184V:DNA:3TC-TP complex. 2020 Scientific reports Figure HIV F160M;M184V 69;75 74;80 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. (c) Structural superimposition of HIV-1 RT3MB:DNA:3TC-TP and the open conformation of RT3MB/F160M/M184V:DNA:3TC-TP colored in yellow. 2020 Scientific reports Figure HIV F160M;M184V 92;98 97;103 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Carbon atoms for 3TC-TP in RT3MB, ETV-TP in RT3MB, and 3TC moiety in RT3MB/F160M/M184V are colored in green, magenta and dark blue, respectively. 2020 Scientific reports Figure HIV F160M;M184V 75;81 80;86 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. N-site structure of RT3MB/F160M/M184V:DNA:3TC-TP ternary complex. 2020 Scientific reports Figure HIV F160M;M184V 26;32 31;37 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Side-chains of Met/Val184 are also shown. 2020 Scientific reports Figure HIV M184V 15 25 32080249 Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine. Structure analyses of HIV-1 RT3MB/RT3MB/F160M/M184V:DNA:NRTIs/dNTPs ternary complex. 2020 Scientific reports Figure HIV F160M;M184V 40;46 45;51 NRTI 56 61 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. 301,426, 301,507, and 302,181 were three CRF01_AE-infected individuals in which both Y181C and L228R mutations were detected at treatment failure (TF) time point. 2020 BMC infectious diseases Figure HIV L228R;Y181C 95;85 100;90 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Black circle represents the percentage of Y181C quasispecies; black square represents the percentage of L228R quasispecies. 2020 BMC infectious diseases Figure HIV L228R;Y181C 104;42 109;47 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Temporal association of Y181C and L228R in CRF01_AE-infected individuals during antiretroviral treatment (ART). 2020 BMC infectious diseases Figure HIV L228R;Y181C 34;24 39;29 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. a The N74D mutation significantly decreased the rate of uncoating among six independent experiments. 2020 Virology journal Figure HIV N74D 6 10 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. b The E45A mutation significantly decreased the rate of uncoating among six independent experiments. 2020 Virology journal Figure HIV E45A 6 10 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. c The compensatory mutation R132T was able to rescue the uncoating kinetics of the E45A mutation to wildtype levels in five independent experiments. 2020 Virology journal Figure HIV E45A;R132T 83;28 87;33 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. d The A92E mutation did not significantly alter the rate of uncoating among seven independent experiments. 2020 Virology journal Figure HIV A92E 6 10 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The effect of CsA on HIV-GFP and N74D infectivity in the parent CHME3 cell line was determined by comparing CsA washout and EtOH washout at times corresponding to the CsA washout assay. 2020 Virology journal Figure HIV N74D 33 37 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The presence of CsA decreases the infectivity of both HIV-GFP and N74D virus at all time points tested. 2020 Virology journal Figure HIV N74D 66 70 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. (C,D,E) The superposition of the various conformations sampled by the protease at various time instants (0 ns, 50 ns, 100 ns, 125 ns, 150 ns, 175 ns, 200 ns) in G40E, G40R and RIT-bound (RIT is shown in red in line representation) protease simulations. 2020 Scientific reports Figure HIV G40E;G40R 161;167 165;171 PR;PR 70;231 78;239 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Hydrogen-bonding map computed from the equilibrated region of the trajectories of (A) WT-free, (B) G40E, (C) G40R and (D) Ab-bound proteases. 2020 Scientific reports Figure HIV G40E;G40R 97;107 103;113 PR 131 140 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The representative structure of the (A) WT-free and (B) G40E proteases are shown in trace representation, highlighting and comparing the hydrogen-bonds and salt-bridges that are weakened or lost and strengthened or new (as explained in Methods) for the functionally important regions individually (i) Elbow, (ii), Active site (iii) Cantilever, (iv) Dimer interface and (v) Flaps. 2020 Scientific reports Figure HIV G40E 54 60 PR 61 70 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The RMSF for the Calpha atoms of the both the chains (A,B) of HIV-1 protease in the WT-free protease (blue), Protease: Ab complex (orange), Protease:RIT complex(green), G40R (yellow) and G40E (purple) mutant protease simulations. 2020 Scientific reports Figure HIV G40E;G40R 187;169 191;173 PR;PR;PR;PR;PR 68;92;109;140;208 76;100;117;148;216 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. 2 days later edited CD4+ T cell pools were infected with GFP reporter HIV viruses (WT, N74D or A77V) and infection levels assayed 2 days later by flow cytometry. 2020 PLoS pathogens Figure HIV A77V;N74D 95;87 99;91 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. 2 days later edited CD4+ T cell pools were infected with GFP reporter HIV-1 viruses (WT, N74D or P90A) and infection levels assayed 2 days later by flow cytometry. 2020 PLoS pathogens Figure HIV N74D;P90A 89;97 93;101 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. 2 days post-electroporation edited CD4+ T cell pools were infected with GFP reporter HIV-1 viruses (WT or N74D) and infection levels assayed 2 days later by flow cytometry. 2020 PLoS pathogens Figure HIV N74D 106 110 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. A: Representative images for mock-infected cells (top row), WT-infected cells (middle row), and N74D-infected cells (bottom row). 2020 PLoS pathogens Figure HIV N74D 96 100 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. A: THP-1 cells stably-overexpressing TRIM34 (gray bars) or control cells (white bars) were infected with WT, N74D or A77V HIV-1 and levels of infection assayed 2 days post-infection by flow cytometry. 2020 PLoS pathogens Figure HIV A77V;N74D 117;109 121;113 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. B and C: Two replicates of the WT and N74D screens (C) were performed while the P90A screen (B) includes only a single replicate. 2020 PLoS pathogens Figure HIV N74D;P90A 38;80 42;84 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. B: Quantification of percent p24gag+ colocalizing with both TRIM34 and TRIM5alpha for the WT and N74D virus. 2020 PLoS pathogens Figure HIV N74D 97 101 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. C: An HIV-CRISPR screen (with the ISG-enriched PIKAHIV library) was performed with a single replicate in THP-1 cells without any IFN treatment for the N74D capsid mutant virus. 2020 PLoS pathogens Figure HIV N74D 151 155 Capsid 156 162 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. C: THP-1 cells stably-overexpressing TRIM34 (gray bars) or control cells (white bars) were infected with WT, N74D or N57A HIV-1 and levels of infection assayed 2 days post-infection by flow cytometry. 2020 PLoS pathogens Figure HIV N57A;N74D 117;109 121;113 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Cell pools were infected with the N74D-LUC virus (A) or WT-LUC virus (B) and levels of infection assayed 2 days post-infection by luciferase assay (Relative Luciferase Units). 2020 PLoS pathogens Figure HIV N74D 34 38 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Cell populations were sorted for dTomato expression and, following recovery, were infected with VSV-G pseudotyped WT or N74D Luciferase reporter viruses (HIV-1LAI CA-WT LUC or HIV-1LAI CA-N74D LUC). 2020 PLoS pathogens Figure HIV N74D;N74D 120;188 124;192 Capsid;Capsid 163;185 165;187 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Edited cells were infected with either WT or N74D HIV and the amount of HIV replication assayed by analysis of GFP+ cells 2 days post-infection after overnight IFN treatment (A) or in untreated cells (no IFN) (B). 2020 PLoS pathogens Figure HIV N74D 45 49 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. F and G: THP-1 cells stably-overexpressing rhesus macaque TRIM34 (mac TRIM34:gray bars) or control cells (white bars) were infected with WT (F) or N74D (G) HIV-1 and levels of infection assayed 2 days post-infection by luciferase assay. 2020 PLoS pathogens Figure HIV N74D 147 151 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. F: TRIM34-overexpressing cells (gray bars) or control cells (white bars) were infected with VSV/G-pseudotyped HIV-1LAI CA-WT LUC or HIV-1LAI CA-N74D LUC viruses with or without Nevirapine (NVP) to inhibit HIV reverse transcription. 2020 PLoS pathogens Figure HIV N74D 144 148 RT;Capsid;Capsid 209;119;141 230;121;143 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. HIV-CRISPR cells were infected with either WT HIV-1LAI, the HIV-1 N74D capsid mutant (HIV-1LAI CA-N74D) or the HIV-1 P90A capsid mutant (HIV-1LAI CA-P90A). 2020 PLoS pathogens Figure HIV N74D;P90A 98;149 102;153 Capsid;Capsid;Capsid;Capsid 71;122;95;146 77;128;97;148 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. HIV-CRISPR screening identifies TRIM5alpha and TRIM34 as restriction factors for HIV-1 capsid mutant viruses, P90A and N74D. 2020 PLoS pathogens Figure HIV N74D;P90A 119;110 123;114 Capsid 87 93 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. The pooled cells were challenged with VSV-G pseudotyped HIV-1 vectors expressing GFP reporter and containing CA-N74D (D), WT CA (E), or CA-P90A (F), across a range of viral inputs normalized for RT activity (RTU: Reverse Transcriptase Units/mL). 2020 PLoS pathogens Figure HIV N74D;P90A 112;139 116;143 RT;Capsid;Capsid;Capsid;RT 213;109;125;136;195 234;111;127;138;197 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. The Top 200 Gene hits for each capsid mutant virus (CA-P90A or CA-N74D) along with corresponding scores for the WT virus are shown (the same data is used for WT in both B and C). 2020 PLoS pathogens Figure HIV N74D;P90A 66;55 70;59 Capsid;Capsid;Capsid 31;52;63 37;54;65 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. They were plated on coverslips and synchronously infected with VSV-G pseudotyped HIV-1 with WT or N74D viruses as indicated. 2020 PLoS pathogens Figure HIV N74D 98 102 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. TRIM34 requires TRIM5alpha to restrict the N74D virus. 2020 PLoS pathogens Figure HIV N74D 43 47 32309558 The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics. Change in the van der Waals volume induced by the drug resistance mutations I47V and V32I. 2014 Discoveries (Craiova, Romania) Figure HIV I47V;V32I 76;85 80;89 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Sequences are indicated by symbols corresponding to their NNRTI resistance mutation patterns: K103R + V179D (triangle), K103R + V179E (circle) 2020 BMC infectious diseases Figure HIV K103R;K103R;V179D;V179E 94;120;102;128 99;125;107;133 NNRTI 58 63 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Sequences are indicated by symbols corresponding to their NNRTI resistance mutation patterns: K103R + V179D (triangle), K103R + V179E (circle). 2020 BMC infectious diseases Figure HIV K103R;K103R;V179D;V179E 94;120;102;128 99;125;107;133 NNRTI 58 63 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. (A) Change in backbone RMSD for the WT, E92Q, G140S and Y143R systems plotted over 300 ns. 2020 PloS one Figure HIV E92Q;G140S;Y143R 40;46;56 44;51;61 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. (B) Change in RMSF for the C-alpha residues for the WT, E92Q, G140S and Y143R systems plotted over the last 200ns. 2020 PloS one Figure HIV E92Q;G140S;Y143R 56;62;72 60;67;77 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. (C) Measure of compactness for the WT, E92Q, G140S and Y143R systems plotted over the last 200 ns. 2020 PloS one Figure HIV E92Q;G140S;Y143R 39;45;55 43;50;60 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. (B) Middle panel indicates the effect of the Q563R change in disrupting the six-helix bundle, resulting in an infectivity defect. 2020 PLoS pathogens Figure HIV Q563R 45 50 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. A single-residue change in the gp41 region (Q563R) of Env E1 is responsible for the increased infection observed specifically with HIV-positive plasma. 2020 PLoS pathogens Figure HIV Q563R 44 49 gp41;Env 31;54 35;57 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Monoclonal antibodies targeting HR1 and the C-C loop of gp41 restore infectivity defects observed with Q563R. 2020 PLoS pathogens Figure HIV Q563R 103 108 gp41 56 60 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Q563R reduces Env infectivity by disrupting membrane fusion and six-helix bundle formation. 2020 PLoS pathogens Figure HIV Q563R 0 5 Env 14 17 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Viruses with Q563R Envs exhibit increased sensitivity to neutralization by MPER bNAbs. 2020 PLoS pathogens Figure HIV Q563R 13 18 Env 19 23 32528834 Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Final geometries for 26 in complexs with WT (A), K103N (B) and RES056 (C) RT. 2020 Acta pharmaceutica Sinica. B Figure HIV K103N 49 54 RT 74 76 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. (a) HIV-1 GFP WT or N74D vector titre on HEK293 cells untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)). 2020 eLife Figure HIV N74D 20 24 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. (a) HIV-1 GFP WT or P90A vector titre in HEK293 untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)). 2020 eLife Figure HIV P90A 20 24 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. (b) HIV-1 GFP P90A RT products, 2LTR circles and proviral DNA in HEK293 untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)). 2020 eLife Figure HIV P90A 14 18 RT 19 21 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. (f) HIV-1 GFP WT (left) or P90A (right) vector titre on HEK293 cells untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)) after CsA was added at the stated times after infection. 2020 eLife Figure HIV P90A 27 31 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. (f) HIV-1 GFP WT (left) or P90A (right) vector titre on HEK293 cells untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)) and depleted of TNPO3 by shRNA transduction. 2020 eLife Figure HIV P90A 27 31 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. (i) HIV-1 GFP WT (left) or P90A (right) vector titre on HEK293 cells untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)) and depleted of Nup358 by shRNA transduction. 2020 eLife Figure HIV P90A 27 31 32576136 Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study. Note: PIs mutations: M46I, I54V, V82A, K20T, L10F/LFI and Q58E/QE; NRTIs mutations: D67N/DN, K70R/KR/T, M184V/MV/I, T215F/FS/TNSY, K219Q, K65R, L74I/LI/LV, Y115F, L210W, M41L and V75I; NNRTIs mutation: A98G/AG, K101E/N/KN, K103N/KN, V108I, V106M, Y181C/YC/I, H221Y, Y188L/YH/YFHL, F227L/FL, P225H, L100I/LI, G190A, E138Q, V179D/E, M230L/ML and V106M/VM. 2020 BMC infectious diseases Figure HIV A98A;A98G;D67D;D67N;E138Q;F227F;F227L;G190A;H221Y;I54V;K101E;K101K;K101N;K103K;K103N;K20T;K219Q;K65R;K70K;K70R;K70T;L100I;L10F;L10I;L10L;L210W;L74I;L74L;L74V;M184I;M184M;M184V;M230L;M41L;M46I;P225H;Q58E;T215F;T215N;T215S;T215T;T215Y;V106M;V106M;V108I;V179D;V179E;V75I;V82A;Y115F;Y181C;Y181I;Y188F;Y188H;Y188L;Y188Y;A98A;F227F;K103K;L100L;L10I;L10L;M230M;Q58Q;V106V;Y181Y 202;202;84;84;315;281;281;308;259;27;211;211;211;223;223;39;131;138;93;93;93;298;45;45;45;163;144;144;144;104;104;104;331;170;21;291;58;116;116;116;116;116;240;344;233;322;322;179;33;156;247;247;266;266;266;266;202;281;223;298;45;45;331;58;344;247 208;208;91;90;320;288;288;313;264;31;221;221;221;230;230;43;136;142;102;102;102;305;51;51;51;168;154;154;154;114;114;114;338;174;25;296;64;129;129;129;129;129;245;351;238;329;329;183;37;161;257;257;279;279;279;279;209;289;231;306;53;53;339;65;352;257 NNRTI;NRTI;PI 185;67;6 191;72;9 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. (A) Generation of Ld W97R mutant mouse by CRISPR-EZ. 2020 Frontiers in immunology Figure HIV W97R 21 25 32733483 An Unusual MHC Molecule Generates Protective CD8+ T Cell Responses to Chronic Infection. Sequences show an example of a wild-type B6.C mouse compared to an Ld W97R mutant mouse generated by sequencing DNA from the tail. 2020 Frontiers in immunology Figure HIV W97R 70 74 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. (a) Representative flow cytometric analysis of surface expression of tetherin on primary CD4 T cells infected with wild type SIVmac239 or SIVmac239 harboring the H196Q variant alone or in combination with the E191R variant. 2020 PloS one Figure HIV E191R;H196Q 209;162 214;167 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. The E191R variant restores tetherin downregulation lost with the H196Q variant in SIVmac239. 2020 PloS one Figure HIV E191R;H196Q 4;65 9;70 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. (E) Infectivity of the infectious viruses of SIVcpzPtt MB897 WT, M16E and E2X (vif deleted) derivatives. 2020 PLoS pathogens Figure HIV E2X;M16E 74;65 77;69 Vif 79 82 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. (J) Importance of M16E substitution in other SIVcpzPtt strains to counteract gA3G. 2020 PLoS pathogens Figure HIV M16E 18 22 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Statistically significant differences (P < 0.05) versus "CP2139" (B-D), "M16E" (G and H) or "WT" (J) are shown by red asterisks. 2020 PLoS pathogens Figure HIV M16E 73 77 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. The infectious viruses of SIVcpzPtt MB897 WT, M16E and E2X (vif-deleted) derivatives were inoculated into parental SupT11-CCR5 cells (G) or the SupT11-CCR5-gA3G (H) at MOI 0.1. 2020 PLoS pathogens Figure HIV E2X;M16E 55;46 58;50 Vif 60 63 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Cluster centroids of the WT, N155H, and N155H+Q148H complexes. 2020 Frontiers in molecular biosciences Figure HIV N155H;N155H;Q148H 29;40;46 34;45;51 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. Panel (A) shows the whole complex, and the red dotted circle indicates the localization of chain (A) active site; panels (B-D) show the coordination site of the Mg2+ ions in chain A from one of the cluster centroids of WT, N155H, and N155H+Q148H, respectively. 2020 Frontiers in molecular biosciences Figure HIV N155H;N155H;Q148H 223;234;240 228;239;245 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. RMSD of each replica of the WT, N155H, and N155H+Q148H systems. 2020 Frontiers in molecular biosciences Figure HIV N155H;N155H;Q148H 32;43;49 37;48;54 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. RMSF of WT is shown in red, N155H in green, and the double mutant in black. 2020 Frontiers in molecular biosciences Figure HIV N155H 28 33 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. RMSF of WT, N155H, and N155H+Q148H. 2020 Frontiers in molecular biosciences Figure HIV N155H;N155H;Q148H 12;23;29 17;28;34 32974383 Evidence for Disruption of Mg(2+) Pair as a Resistance Mechanism Against HIV-1 Integrase Strand Transfer Inhibitors. The superposition of the cluster centroids from all the systems is shown in (A); WT, N155H, and N155H+Q148H are shown, respectively, in red, green, and black; panel (B) shows the cluster centroids individually. 2020 Frontiers in molecular biosciences Figure HIV N155H;N155H;Q148H 85;96;102 90;101;107 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. (a) Differences in CD4+ cell count between responders and nonresponders to SL9-1K/SL9-1Q epitopes among Pol S653K/Q-infected individuals. 2021 AIDS (London, England) Figure HIV S653K;S653Q 108;108 115;115 Pol 104 107 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. (a) Longitudinal changes in epitope sequence and CD4+ cell count in a Pol S653K-infected individual (VI-065). 2021 AIDS (London, England) Figure HIV S653K 74 79 Pol 70 73 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. (b) Differences in CD4+ cell count between three groups (wild-type-infected responders to SL9 peptide + Pol S653K/Q-infected responders to SL9-1K/SL9-1Q peptides, Pol S653A/T/L-infected responders to SL9 peptide, and nonresponders). 2021 AIDS (London, England) Figure HIV S653A;S653K;S653L;S653Q;S653T 167;108;167;108;167 176;115;185;115;176 Pol;Pol 104;163 107;166 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. (b) T-cell responses to the SL9 epitope in individuals infected with mutants at Pol 653 other than Pol S653A/T/L. 2021 AIDS (London, England) Figure HIV S653A;S653L;S653T 103;103;103 112;112;112 Pol;Pol 80;99 83;102 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. (d) Recognition by 1K/1Q-specific T cells of cells infected with Pol S653K, S653 (wild-type), and S653A/T/L viruses. 2021 AIDS (London, England) Figure HIV S653A;S653K;S653L;S653T 98;69;98;98 107;74;107;107 Pol 65 68 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. (d) T-cell responses to SL9-1K and SL9-1Q epitope peptides in Pol S653K/Q-infected individuals. 2021 AIDS (London, England) Figure HIV S653K;S653Q 66;66 73;73 Pol 62 65 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. (f) Recognition of cells infected with S653K or S653Q viruses by 1K/1Q-specific T cells. 2021 AIDS (London, England) Figure HIV S653K;S653Q 39;48 44;53 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Bulk T cells were stimulated with CD4-expressing 721.221-C1505 cells infected with 93JP-NH1Pol S653 (wild-type), 93JP-NH1Pol S653A, 93JP-NH1Pol S653T, or 93JP-NH1Pol S653L, and IFN-gamma production from the T cells was measured by performing the intracellular cytokine staining assay. 2021 AIDS (London, England) Figure HIV S653A;S653L;S653T 125;166;144 130;171;149 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Comparison of CD4+ cell count between HLA-C*15:05-positive individuals infected with Pol S653 (wild-type) virus and those with each of Pol S653A, Pol S653T, Pol S653L, Pol I655V, and Pol K657R (a) or with at least one of the Pol S653A/T/L mutant viruses (b). 2021 AIDS (London, England) Figure HIV I655V;K657R;S653A;S653A;S653L;S653L;S653T;S653T 172;187;229;139;229;161;229;150 177;192;238;144;238;166;238;155 Pol;Pol;Pol;Pol;Pol;Pol;Pol 85;135;146;157;168;183;225 88;138;149;160;171;186;228 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Effects of Pol S653A, Pol S653T, and Pol S653L on CD4+ cell count and T-cell recognition. 2021 AIDS (London, England) Figure HIV S653A;S653L;S653T 15;41;26 20;46;31 Pol;Pol;Pol 11;22;37 14;25;40 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. For patient VI-136 infected with a mixture of S653K/Q viruses, T-cell responses to both 1K and 1Q peptides were analyzed. 2021 AIDS (London, England) Figure HIV S653K;S653Q 46;46 53;53 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Frequencies of individuals infected with wild-type, Pol S653A/T/L, S653K/Q, or S653F/H/I/N/Y virus in 74 HLA-C*15:05+ individuals are shown. 2021 AIDS (London, England) Figure HIV S653A;S653F;S653H;S653I;S653K;S653L;S653N;S653Q;S653T;S653Y 56;79;79;79;67;56;79;67;56;79 65;92;92;92;74;65;92;74;65;92 Pol 52 55 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Impact of Pol S653A/T/L mutations on HIV-1 suppression by T cells specific for the SL9 epitope. 2021 AIDS (London, England) Figure HIV S653A;S653L;S653T 14;14;14 23;23;23 Pol 10 13 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Longitudinal changes in epitope sequence and T-cell responses in a Pol S653K-infected individual. 2021 AIDS (London, England) Figure HIV S653K 71 76 Pol 67 70 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Proportions of 721.221-C1505 cells infected with 93JP-NH1Pol S653 (wild-type), 93JP-NH1Pol S653A, 93JP-NH1Pol S653T, and 93JP-NH1Pol S653L were 93.2, 94.9, 93.6, and 88.7%, respectively. 2021 AIDS (London, England) Figure HIV S653A;S653L;S653T 91;133;110 96;138;115 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Proportions of 721.221-C1505 cells infected with 93JP-NH1Pol S653K and 93JP-NH1Pol S653Q were 90.0 and 95.7%, respectively. 2021 AIDS (London, England) Figure HIV S653K;S653Q 61;83 66;88 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Proportions of 721.221-C1505 cells infected with 93JP-NH1Pol S653K, 93JP-NH1Pol S653(WT), 93JP-NH1Pol S653A, 93JP-NH1Pol S653T, and 93JP-NH1Pol S653L were 54.6, 29.1, 88.2, 62.4, and 64.8%, respectively. 2021 AIDS (London, England) Figure HIV S653A;S653K;S653L;S653T 102;61;144;121 107;66;149;126 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. T-cell responses of the bulk T cells, established from two Pol S653K-infected individuals (VI-003 and VI-114) or one S653Q-infected individual (VI-231), to 1K or 1Q peptide-prepulsed 721.221-C1505 cells were analyzed by performing the intracellular cytokine staining assay. 2021 AIDS (London, England) Figure HIV S653K;S653Q 63;117 68;122 Pol 59 62 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. T-cell responses to SL9-1K and SL9-1Q peptides were analyzed in PolS653K-infected and S653Q-infected individuals, respectively. 2021 AIDS (London, England) Figure HIV S653Q 86 91 Pol 64 67 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. The bulk T cells were stimulated with CD4-expressing 721.221-C1505 cells infected with 93JP-NH1Pol S653K, 93JP-NH1Pol S653(WT), 93JP-NH1Pol S653A, 93JP-NH1Pol S653T, or 93JP-NH1Pol S653L; and IFN-gamma production from the T cells was measured by using the intracellular cytokine staining assay. 2021 AIDS (London, England) Figure HIV S653A;S653K;S653L;S653T 140;99;181;159 145;104;186;164 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. The bulk T cells were stimulated with CD4-expressing 721.221-C1505 cells infected with 93JP-NH1Pol S653K, or 93JP-NH1Pol S653Q; and IFN-gamma production from the T cells was measured by using the intracellular cytokine staining assay. 2021 AIDS (London, England) Figure HIV S653K;S653Q 99;121 104;126 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (A) Effect of TRIM5 knockout on the ability of HIV-1 CA P90A and WT HIV-1 to infect THP-1 macrophages. 2020 PLoS pathogens Figure HIV P90A 56 60 Capsid 53 55 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (B,C) THP-1 cells were primed with HIV-1 CA P90A (CrFK MOI = 3) prior to challenge with different CrFK MOI of WT HIV-1. 2020 PLoS pathogens Figure HIV P90A 44 48 Capsid 41 43 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (C) The relative restriction imposed by P90A priming in control THP-1 macrophages or in THP-1 cell lines knocked out for the indicated genes as shown in (A,B). 2020 PLoS pathogens Figure HIV P90A 40 44 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (D) The impact of NF-kappaB, AP1, and autophagy inhibition on P90A-induced restriction. 2020 PLoS pathogens Figure HIV P90A 62 66 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (E) Differentiated THP-1 cells were primed or not with HIV-1 CA WT (TRIM5 resistant) or P90A (TRIM5 sensitive) and then challenged with HIV-1 GFP. 2020 PLoS pathogens Figure HIV P90A 88 92 Capsid 61 63 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (F) The effect of TRIM5 knockout on the ability of priming with HIV-1 CA P90A to protect THP-1 macrophages from infection with WT HIV-1 GFP. 2020 PLoS pathogens Figure HIV P90A 73 77 Capsid 70 72 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (G) The relative restriction seen in P90A primed WT or TRIM5 KO THP-1 macrophages stably expressing APEX2 or TRIM5-APEX2 (TRIM5 add-back). 2020 PLoS pathogens Figure HIV P90A 37 41 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. (H) Q-RT PCR analysis of the impact of P90A (CrFK MOI = 3) or poly(I:C) priming on the permissivity of WT or TRIM5 KO THP-1 macrophages to Sendai virus infection. 2020 PLoS pathogens Figure HIV P90A 39 43 RT 6 8 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Control or knockout THP-1 macrophages were primed with P90A (CrFK MOI 3) for 24 hours prior to infection with WT HIV-GFP (CrFK MOI 1) for two days. 2020 PLoS pathogens Figure HIV P90A 55 59 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. The percentage of cells showing red fluorescence (P90A) or green fluorescence (HIV WT) was determined by high content imaging 2 days post infection. 2020 PLoS pathogens Figure HIV P90A 50 54 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. THP-1 cell lines knocked out for the autophagy factors ULK1, BECN1, ATG7 or TRIM5 (or control) were PMA-differentiated and then exposed to HIV-1 CA P90A for two hours (CrFK MOI = 3) prior to RNA isolation and qPCR analysis. 2020 PLoS pathogens Figure HIV P90A 148 152 Capsid 145 147 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. THP-1 cells were treated with BAY 117085 (NF-kappaB inhibitor; 10 muM), SP600125 (JNK/AP1 inhibitor; 10 muM) or 3-methyladenine (PI3 kinase/autophagy inhibitor; 1 mM) or DMSO (vehicle control) for 1 h prior to infection with P90A or mock infection. 2020 PLoS pathogens Figure HIV P90A 225 229 PI 129 131 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. (B) Comparison of replication capacity over multiple rounds of infection for wild-type Ba-L versus mutant bearing the 4-amino-acid Gag matrix signature T122A/G123E/126del/127del. 2020 mBio Figure HIV G123E;T122A 158;152 163;157 Matrix;Gag 135;131 141;134 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Gag 126del and 127del mutations occurring with T122A and G123E confer resistance to the protease inhibitor lopinavir in the absence of any major protease mutations. 2020 mBio Figure HIV 126del;127del;G123E;T122A 4;15;57;47 10;21;62;52 PR;PR;Gag 88;145;0 96;153;3 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. V128del was also added, as this deletion is present in HIV-1 CRF02_AG. 2020 mBio Figure HIV V128del 0 7 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. (B) Specific SERINC3/5 counteraction function of NefSF2 and the indicated mutants (Y120F, Q125H, Y120F/Q125H). 2020 Scientific reports Figure HIV Q125H;Q125H;Y120F;Y120F 90;103;83;97 95;108;88;102 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Ability of NefSF2 and the indicated mutants (F121A and D123A) to counteract SERINC3/5 was determined by dividing the relative infectivity of viral particles secreted from JTAg cells by that from JTAg-SERINC3/5-/- cells (right panel). 2020 Scientific reports Figure HIV D123A;F121A 55;45 60;51 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Effects of Nef Y120F and Q125H mutations on counteraction of SERINC3/5-mediated infectivity inhibition. 2020 Scientific reports Figure HIV Q125H;Y120F 25;15 30;20 Nef 11 14 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Effects of Nef Y120F/Q125H mutations on viral replication in PBMC. 2020 Scientific reports Figure HIV Q125H;Y120F 21;15 26;20 Nef 11 14 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Effects of Y120F and Q125H mutations in patient-derived Nef clones on counteraction of SERINC3/5-mediated infectivity inhibition and modulation of cell surface receptor expression. 2020 Scientific reports Figure HIV Q125H;Y120F 21;11 26;16 Nef 56 59 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Those cells were transduced with HIV-1 NL43 proviral constructs lacking Nef (DeltaNef) or carrying NefSF2 and the mutants (F121A and D123A), and then TZM-bl cells were exposed to the resultant viruses to determine viral infectivity. 2020 Scientific reports Figure HIV D123A;F121A 133;123 138;129 Nef 72 75 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. Overall, 0.4% of the patients had drug resistance-associated mutations to G163K and E138A. 2020 Infection and drug resistance Figure HIV E138A;G163K 84;74 89;79 33364799 Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naive Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan. The figure shows that the most common drug resistance-associated mutations were M184V (1.3%) and K65R (1.3%) for NRTIs, V179D (4.5%), V106I (2.7%) and K103N (1.3%) for NNRTIs, and L10I (13.4%) and A71T (5.8%) for PIs. 2020 Infection and drug resistance Figure HIV A71T;K103N;K65R;L10I;M184V;V106I;V179D 197;151;97;180;80;134;120 201;156;101;184;85;139;125 NNRTI;NRTI;PI 168;113;213 174;118;216 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. (D) Representative structures of the CypA-binding loop from the simulations with positively charged H219 (left) and mutant H219Q (right) calculated using cluster analysis. 2021 Computational and structural biotechnology journal Figure HIV H219Q 123 128 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. (D) Snapshot from simulations of mutant 7 (Simulation 4 in Table S2) showing PIP2 binding facilitated by E40K mutation, displayed in similar colours and representation as in (C). 2021 Computational and structural biotechnology journal Figure HIV E40K 105 109 PI 77 79 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Data taken from two independent simulations of CA with neutral H219 (black), protonated H219 (blue) and H219Q mutant (red). 2021 Computational and structural biotechnology journal Figure HIV H219Q 104 109 Capsid 47 49 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Red arrows show transient dissociation of CypA from CA in H219Q mutant simulations. 2021 Computational and structural biotechnology journal Figure HIV H219Q 58 63 Capsid 52 54 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Simulation with neutral H219 is shown in black, positively charged H219 in blue, and mutant H219Q in red. 2021 Computational and structural biotechnology journal Figure HIV H219Q 92 97 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. The position of mutant residue, L75R, is shown in pink stick representation, whereas PIP2 is shown in orange surface representation. 2021 Computational and structural biotechnology journal Figure HIV L75R 32 36 PI 85 87 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. The role of the Q199H mutation in CA oligomerisation. 2021 Computational and structural biotechnology journal Figure HIV Q199H 16 21 Capsid 34 36 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Association of Vif Q135P with rapid progression. 2021 Journal of ginseng research Figure HIV Q135P 19 24 Vif 15 18 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. Q135P was found in Donor O and eight HPs. 2021 Journal of ginseng research Figure HIV Q135P 0 5 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. B, surface representation of the trimer arrangement of the myr(-)MA Q63R protein. 2021 The Journal of biological chemistry Figure HIV Q63R 68 72 Matrix 65 67 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. C, cartoon representation of myr(-)MA Q63R mutant showing the H-bond formed between the side chains of Arg63 and Ser67. 2021 The Journal of biological chemistry Figure HIV Q63R 38 42 Matrix 35 37 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. High-resolution crystal structure of the HIV-1 myr(-)MA Q63R protein.A, superposition of WT myr(-)MA trimer protein (PDB code 1HIW; blue) and the two trimers found in the asymmetric unit of the crystal structure of myr(-)MA Q63R (yellow and gray). 2021 The Journal of biological chemistry Figure HIV Q63R;Q63R 56;224 60;228 Matrix;Matrix;Matrix 53;98;221 55;100;223 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The structure of the myr(-)MA Q63R mutant is essentially identical to that of the WT myr(-)MA protein. 2021 The Journal of biological chemistry Figure HIV Q63R 30 34 Matrix;Matrix 27;91 29;93 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. (a) Changes of NanoDSF-derived melting temperature (DeltaTm's) of K25A, K25N, R18G and R18G/K25A in the presence of different polyanions compared to the respective disulfide-stabilised hexamers in absence of ligands. 2021 PLoS pathogens Figure HIV K25A;K25A;K25N;R18G;R18G 66;92;72;78;87 70;96;76;82;91 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. (b) Dissociation constants (KD's) of Atto488-ATP binding to self-assembled CA A204C/A92E cones determined by TIRF microscopy. 2021 PLoS pathogens Figure HIV A204C;A92E 78;84 83;88 Capsid 75 77 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. (c) Cryo-ET analysis of infectious WT or K25A HIV virions. 2021 PLoS pathogens Figure HIV K25A 41 45 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. (d) Matching infectivity (GFP +ve cell area) and reverse transcription (strong-stop, RU5, at 4 hours post-infection) of chimeric viruses produced with an increasing ratio of WT:K25A Gag. 2021 PLoS pathogens Figure HIV K25A 177 181 RT;Gag 49;182 70;185 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. CA K25A mutant capsids fall apart rapidly and IP6 does not stabilise CA K25A or K25R capsids, unlike wild type capsids. 2021 PLoS pathogens Figure HIV K25A;K25A;K25R 3;72;80 7;76;84 Capsid;Capsid;Capsid;Capsid;Capsid 15;85;111;0;69 22;92;118;2;71 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Cells expressing Rhesus TRIM5 were infected with a consistent dose of WT GFP-expressing virus and increasing doses of RFP-expressing WT, K25A and K25R viruses. 2021 PLoS pathogens Figure HIV K25A;K25R 137;146 141;150 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Scalebar: 200 nm (g) Assembly reactions of 250 muM WT or K25A CA in 50 mM MES pH 6, 100 mM NaCl and a range of IP6 concentrations up to 10 mM. 2021 PLoS pathogens Figure HIV K25A 57 61 Capsid 62 64 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. WT and K25A cores with and without IP6 (50 muM). 2021 PLoS pathogens Figure HIV K25A 7 11 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. The INSTIs were docked to a homology model of WT and G140S+Q148H mutant HIV-1 IN based on cryo-EM structures (SIVrcm IN) using Prime in Schrodinger Suite 2019-2 (Schrodinger, LLC, New York, NY) and a knowledge-based approach. 2021 Antimicrobial agents and chemotherapy Figure HIV G140S;Q148H 53;59 58;64 INSTI;IN;IN 4;78;117 10;80;119 33649107 Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. Viral replication of WT (A) and G140S+Q148H (B) variants after treatment with DTG, BIC, EVG, and RAL following drug washout (Delta) starting at washout day 0 (3 days postinfection). 2021 Antimicrobial agents and chemotherapy Figure HIV G140S;Q148H 32;38 37;43 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. a HEK-293 T cells were transfected with the HIV-1 subtype C clones, K3016 WT and its mutants SP1: N9S, SP1:G10T and SP1:N9S/G10T. 2021 Retrovirology Figure HIV G10T;N9S;N9S 124;98;120 128;101;123 SP1;SP1;SP1 93;103;116 96;106;119 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. a HEK-293 T cells were transfected with the HIV-1 subtype C clones, ZM247 WT and its mutants SP1:S9N, SP1:T10G and SP1:S9N/T10G. 2021 Retrovirology Figure HIV T10G;S9N 123;119 127;122 SP1;SP1;SP1 93;102;115 96;105;118 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. a HEK-293T cells were transfected with the HIV-1 subtype C clones, IndieC1 WT and its mutants SP1:S9N, SP1:T10G and SP1:S9N/T10G. 2021 Retrovirology Figure HIV T10G;S9N 124;120 128;123 SP1;SP1;SP1 94;103;116 97;106;119 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. b TZM-bl cells were infected with p24 normalized HIV-1 subtype C viruses IndieC1 WT and its mutants SP1:S9N, SP1:T10G and SP1:S9N/T10G produced from MI treated HEK-293T cells for 48 h to measure infectivity. 2021 Retrovirology Figure HIV T10G;S9N 130;126 134;129 p24;SP1;SP1;SP1 34;100;109;122 37;103;112;125 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. b TZM-bl cells were infected with p24 normalized HIV-1 subtype C viruses K3016 WT and its mutants, SP1:N9S, SP1:G10T and SP1:N9S/G10T produced from MI treated HEK-293T cells for 48 h to measure infectivity. 2021 Retrovirology Figure HIV G10T;N9S 129;125 133;128 p24;SP1;SP1;SP1 34;99;108;121 37;102;111;124 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. b TZM-bl cells were infected with p24 normalized HIV-1 subtype C viruses ZM247 WT and its mutants SP1:S9N, SP1:T10G and SP1:S9N/T10G produced from MI treated HEK-293T cells for 48 h to measure infectivity. 2021 Retrovirology Figure HIV T10G;S9N 128;124 132;127 p24;SP1;SP1;SP1 34;98;107;120 37;101;110;123 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. c The HUT-R5 T-cells were transfected with the HIV-1 Subtype C molecular clone K3016 WT and K3016 CA: I201V mutant. 2021 Retrovirology Figure HIV I201V 102 107 Capsid 98 100 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. c The HUT-R5 T-cells were transfected with the HIV-1 subtype C molecular clone K3016 WT and K3016 SP1: A1V mutant. 2021 Retrovirology Figure HIV A1V 103 106 SP1 98 101 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. HEK-293 T cells were transfected with the HIV-1 subtype C K3016 WT and K3016 SP1: A1V mutant. 2021 Retrovirology Figure HIV A1V 82 85 SP1 77 80 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. HEK-293T cells were transfected with the HIV-1 subtype C K3016 WT and K3016 CA: I201V mutant and treated with 100 nM and 500 nM of the BVM-analog CV-8613 or with DMSO only. 2021 Retrovirology Figure HIV I201V 80 85 Capsid 76 78 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. K3016 CA: I201V mutant is partially resistant and compound-dependent. 2021 Retrovirology Figure HIV I201V 10 15 Capsid 6 8 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. K3016 SP1: A1V mutant is resistant to BVM analog. 2021 Retrovirology Figure HIV A1V 11 14 SP1 6 9 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. Arrow points to location of T8I mutation and CA SP1 and SP1 NC cleavage sites. 2021 Communications biology Figure HIV T8I 28 31 SP1;SP1;NC;Capsid 48;56;60;45 51;59;62;47 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. Both constructs bear the T8I mutation in the SP1 region (T371I in Gag sequence). 2021 Communications biology Figure HIV T371I;T8I 57;25 63;28 SP1;Gag 45;66 48;69 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. CryoET and subtomogram averaging of Gag T8I assemblies and VLPs. 2021 Communications biology Figure HIV T8I 40 43 Gag 36 39 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. T8I mutation stabilizes the six-helix bundle and impairs proteolytic processing of cleavage sites flanking SP1. 2021 Communications biology Figure HIV T8I 0 3 SP1 107 110 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. b T66A HIV-1 CRF02_AG IN showing in total four contacts formed between DTG and one IN residue, one DNA nucleotide and two MG ions. 2021 BMC infectious diseases Figure HIV T66A 2 6 IN;IN 22;83 24;85 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. c T97A HIV-1 CRF02_AG IN showing in total five contacts formed between DTG and two IN residues, one DNA nucleotide and two MG ions. 2021 BMC infectious diseases Figure HIV C97A;T97A 2;2 6;6 IN;IN 22;83 24;85 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. d E157Q HIV-1 CRF02_AG IN showing in total four contacts formed between DTG and one IN residue, two DNA nucleotides and one MG ion. 2021 BMC infectious diseases Figure HIV E157Q 2 7 IN;IN 23;84 25;86 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. e Q148H HIV-1 CRF02_AG IN showing in total five contacts formed between DTG and one IN residue, two DNA nucleotides and two MG ions. 2021 BMC infectious diseases Figure HIV Q148H 2 7 IN;IN 23;84 25;86 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. f R263K HIV-1 CRF02_AG IN showing in total four contacts formed between DTG and one IN residue, one DNA nucleotide and two MG ions. 2021 BMC infectious diseases Figure HIV R263K 2 7 IN;IN 23;84 25;86 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. g N155H HIV-1 CRF02_AG IN showing in total seven contacts formed between DTG and three IN residues, two DNA nucleotides and two MG ions. 2021 BMC infectious diseases Figure HIV N155H 2 7 IN;IN 23;87 25;89 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. h D232N HIV-1 CRF02_AG IN showing in total two contacts formed between DTG and two DNA nucleotides. 2021 BMC infectious diseases Figure HIV D232N 2 7 IN 23 25 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. (A) K103N: R2=0.99339. 2020 AAS open research Figure HIV K103N 2 9 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. (B) M184V: R2=0.99472. 2020 AAS open research Figure HIV M184V 2 9 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Median CD4 (A) and median viral load (B) between samples with detected K103N and samples without K103N mutation. 2020 AAS open research Figure HIV K103N;K103N 71;97 76;102 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Samples with K103N mutation (n=3) 2020 AAS open research Figure HIV K103N 13 18 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Samples with K103N mutation (n=3). 2020 AAS open research Figure HIV K103N 13 18 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Samples without K103N mutation (n=100). 2020 AAS open research Figure HIV K103N 16 21 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. As non-nucleoside reverse transcriptase E138A mutation is not included in the tDRM list, but is associated with significant reduction of susceptibility to rilpivirine, it was marked in violet. 2021 Scientific reports Figure HIV E138A 40 45 NNRTI 3 39 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. (B) Neutralization (measured by ID50 values) of week 30 plasma from two rabbit groups against autologous tier 2 clade A BG505.T332N, tier 1 clade B SF162, and a 12-virus global panel, with MLV included as a negative control. 2021 mBio Figure HIV T332N 126 131 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. (D) Neutralization (measured by ID50 values) of week 30 plasma from three rabbit groups against two respective autologous viruses (Du172.17 and Q842-d12), tier 2 clade A BG505.T332N, tier 1 clade B SF162, and a 12-virus global panel, with MLV included as a negative control. 2021 mBio Figure HIV T332N 176 181 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. (F) Percent neutralization of rabbit plasma against BG505.T332N and its three glycan hole mutants. 2021 mBio Figure HIV T332N 58 63 34156262 Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Color coding in the table indicates the percent reduction relative to the percent neutralization for BG505.T332N (<25%, green; 25 to 50%, yellow; 50 to 75%, orange; >75%, red). 2021 mBio Figure HIV T332N 107 112 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. 20 cloned IN sequences were determined for three viral populations (passages, 2, 10, and 14) in both viral selections, with percentages of resistance Y99H and A128T mutation populations noted. 2021 PLoS pathogens Figure HIV A128T;Y99H 159;150 164;154 IN 10 12 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. A-D Control or IPMK KO single 293T cell clones were transfected with HIV-1WT (A), HIV-1K359A (B), HIV-1T371I (C), or HIV-1K359A/T371I (D) proviral plasmids. 2021 Retrovirology Figure HIV T371I;T371I 103;128 108;133 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. C Single cycle infection assay confirming the identified substitution rescues infectivity of K359A. 2021 Retrovirology Figure HIV K359A 93 98 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. HIV-1K359A/T371I is not impaired by lack of cellular IP6. 2021 Retrovirology Figure HIV T371I 11 16 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. I, J HIV-1WT (I) or HIV-1K359A/T371I (J) virions were titrated on WT MT4 or IPMK KO MT4 cells and infection quantified by flow cytometry. 2021 Retrovirology Figure HIV T371I 31 36 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. C The CRF01_AE cluster with the surveillance drug resistance mutation K103N. 2021 Virology journal Figure HIV K103N 70 75 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. (A-D) Graphs show the levels of early (strong stop) cDNA (upper panels) and late (second strand) cDNA (lower panels) in 293T cells following infection with WT VLP (black line) and mutants P38A (A), P207C/T216C (B), A14C/E45C (C) or M68C/E212C (D). 2021 PLoS pathogens Figure HIV A14C;E212C;E45C;M68C;P207C;P38A;T216C 215;237;220;232;198;188;204 219;242;224;236;203;192;209 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Cells were incubated with primary antibodies to HIV-1 CA and either NUP358 (A-C) or NUP153 (D-F), followed by specific secondary antibodies conjugated to the PLUS and MINUS PLA oligonucleotides (probes). 2021 PLoS pathogens Figure HIV A358C 71 80 Capsid 54 56 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Cellular localisation of CA and IN proteins during WT and A14C/E45C infections. 2021 PLoS pathogens Figure HIV A14C;E45C 58;63 62;67 IN;Capsid 32;25 34;27 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Equal RT units of WT VLP or hyper-stable mutants A14C/E45C, E180C or M68C/E212C VLP were pelleted by centrifugation and resuspended in Laemmli buffer. 2021 PLoS pathogens Figure HIV A14C;E180C;E212C;E45C;M68C 49;60;74;54;69 53;65;79;58;73 RT 6 8 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. HeLa cells were synchronously infected with equal RT units of WT or A14C/E45C mutant (CC in the figure) VLP. 2021 PLoS pathogens Figure HIV A14C;E45C 68;73 72;77 RT 50 52 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. HeLa cells were synchronously infected with equal RT units of WT or A14C/E45C VLP and fixed at 2, 4, 6, 8 and 10 hpi. 2021 PLoS pathogens Figure HIV A14C;E45C 68;73 72;77 RT 50 52 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. HeLa cells were synchronously infected with equal RT units of WT, A14C/E45C, E180C or M68C/E212C VLP and fixed at 16hpi. 2021 PLoS pathogens Figure HIV A14C;E180C;E212C;E45C;M68C 66;77;91;71;86 70;82;96;75;90 RT 50 52 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. New CA mutants with cysteine mutations (E180C, L151C/L189C and K203C/A217C) were designed based on a previously published cryo-EM MDFF atomic model (PDB ID: 3J34) and crystal structures (PDB ID: 3H4E and 3H47). 2021 PLoS pathogens Figure HIV A217C;E180C;K203C;L151C;L189C 69;40;63;47;53 74;45;68;52;58 Capsid 4 6 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. (A) Surface view of the integrase G118R mutant catalytic site (colored by atom with carbons in orange) bound with dolutegravir (rendered in ball-and-stick format and colored by atom with carbons in white). 2022 Antimicrobial agents and chemotherapy Figure HIV G118R 34 39 IN 24 33 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. (B) Ribbon-and-stick rendering of the integrase G118R mutant catalytic site (in green) bound with vDNA (in orange). 2022 Antimicrobial agents and chemotherapy Figure HIV G118R 48 53 IN 38 47 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. (C) The integrase G118R mutant catalytic site (as rendered and oriented in panel B) bound to both vDNA and tDNA substrates (in orange). 2022 Antimicrobial agents and chemotherapy Figure HIV G118R 18 23 IN 8 17 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. (D) Ribbon-and-stick rendering of the integrase catalytic site containing R263K (colored in magenta) and wild-type G118 bound with vDNA and tDNA substrates. 2022 Antimicrobial agents and chemotherapy Figure HIV R263K 74 79 IN 38 47 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. a, K160T was observed in 4 of 13 clones containing G118R, E138K, and R263K integrase substitutions but is not a prespecified dolutegravir resistance-associated substitution. 2022 Antimicrobial agents and chemotherapy Figure HIV E138K;G118R;K160T;R263K 58;51;3;69 63;56;8;74 IN 75 84 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Hydrogen bonding interactions among G118R, the 3' terminus of the tDNA, and the Mg2+ are indicated by dashed yellow lines. 2022 Antimicrobial agents and chemotherapy Figure HIV G118R 36 41 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Hydrogen bonding interactions between N144 with R263 and G118R with E92 are indicated by dashed yellow lines. 2022 Antimicrobial agents and chemotherapy Figure HIV G118R 57 62 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. (B) Identical view of the G118R HIV-1 catalytic site illustrating the hydrogen bonding complex formed among the terminal tDNA, R118 (in pink), and E92 (in pink) with the addition of the G118R resistance mutant. 2022 Antimicrobial agents and chemotherapy Figure HIV G118R;G118R 26;186 31;191 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. (C) Identical view of the L74M/V75A HIV-1 catalytic site illustrating the location of M74 (in pink) and A75 (in pink) relative to the nearby catalytic site residues L63, C65, and F121. 2022 Antimicrobial agents and chemotherapy Figure HIV L74M;V75A 26;31 30;35 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. (D) Identical view of the L74M/V75A/G118R HIV-1 catalytic site illustrating the location of M74 (in pink) and A75 (in pink) relative to R118 (in pink) and E92 (in pink). 2022 Antimicrobial agents and chemotherapy Figure HIV G118R;L74M;V75A 36;26;31 41;30;35 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Cross-resistance of plasma-derived HIV-1 with E138A to non-nucleoside reverse transcriptase inhibitors used for antiretroviral therapy. 2021 Journal of the International AIDS Society Figure HIV E138A 46 51 NNRTI 55 91 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. Fold-change IC50 is also shown for 5 placebo (PLB) arm plasma-derived HIV-1 as follows: PLB-1 is HIV-1K101E/E138A, PLB-2E138A, PLB-3E138A, PLB-4E138A, PLB-5E138A. 2021 Journal of the International AIDS Society Figure HIV E138A;E138A;E138A;E138A 132;144;156;108 137;149;161;113 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. These recombinants are depicted as follows: DPV-1 is HIV-1E138A/V179IT, DPV-2 is HIV-1V108IV/E138A, DPV-3 is HIV-1E138A/V179D. 2021 Journal of the International AIDS Society Figure HIV E138A;V179D;V179I;V179T 93;120;64;64 98;125;70;70 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. (B) Parent V370A. 2022 Antimicrobial agents and chemotherapy Figure HIV V370A 11 16 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. (C) A364V-containing VLP. 2022 Antimicrobial agents and chemotherapy Figure HIV A364V 2 9 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. The mean value for GSK'795 was calculated using 3 fewer samples, as 3 viruses did not have a measurable EC90 (V362I/V370A- and A326T/V362I/V370A-containing viruses and a virus containing the 93BR024 gag/pro gene). 2022 Antimicrobial agents and chemotherapy Figure HIV A326T;V362I;V370A;V362I;V370A 127;133;139;110;116 132;138;144;115;121 Gag 199 202 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Virus was exposed to increasing GSK'254 concentrations originating from parent wild type and V370A variants, and viral genotypes were assessed. 2022 Antimicrobial agents and chemotherapy Figure HIV V370A 93 98 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. The viral load (RNA copies/ml) in HIV-infected patients with pre-existing E138A mutation on RPVbased therapy. 2022 Clinical case reports Figure HIV E138A 74 79 HIV infections 34 46 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (A) SPR binding data for T18A TCR recognition of the wildtype (WT) and popular mutated TL9 presented by HLA-B*81:01. 2022 Frontiers in immunology Figure HIV T18A 25 29 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (A) The "opened" conformation of the beta sheet interactions between Valpha and Jalpha of T18A when it is bound to B8101-pTL9. 2022 Frontiers in immunology Figure HIV T18A 90 94 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (A) the conformational change of HLA-B*81:01/TL9 complex after T18A TCR engagement. 2022 Frontiers in immunology Figure HIV T18A 63 67 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (A) The foot print of T18A TCR CDR3beta on p-HLA complex. 2022 Frontiers in immunology Figure HIV T18A 22 26 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (A) The T18A TCR (T18Aalpha in pale pink, T18Abeta in pale cyan) recognize TL9 epitope presented by HLA-B*81:01. 2022 Frontiers in immunology Figure HIV T18A;T18A;T18L 8;18;18 12;25;25 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (B-E) CDR3beta use in other 4 structures, C12C TCR (PDB: 4G8G), F24 TCR (PDB: 6CQL), KK50.4 TCR (PDB: 2ESV) and DM1 TCR (PDB: 3DXA). 2022 Frontiers in immunology Figure HIV C12C 42 46 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (B, C) the interactions between T18A TCR and HLA-B*81:01/TL9 complex. 2022 Frontiers in immunology Figure HIV T18A 32 36 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (B) The "closed" conformation of Valpha-Jalpha interactions of C12C TCR (PDB: 4G8G) and 1E6 TCR (PDB: 3UTS), representing traditional CDR3alpha conformation in most of TCR-pMHC profiles. 2022 Frontiers in immunology Figure HIV C12C 63 67 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (B) The footprint of T18A TCR on the surface of HLA-B*81:01-TL9 complex. 2022 Frontiers in immunology Figure HIV T18A 21 25 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (D) The Valpha and Vbeta domains of T18A and 1E6 TCR are overlaid by Vbeta as similar TRBV gene is used. 2022 Frontiers in immunology Figure HIV T18A 36 40 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. (E) Detailed interactions of T18A TCR with Gag-TL9 epitope in the context of HLA-B*81:01. 2022 Frontiers in immunology Figure HIV T18A 29 33 Gag 43 46 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. High-affinity T18A TCR bind to TL9 or TL9 escape variants under HLA-B*81:01 restriction. 2022 Frontiers in immunology Figure HIV T18A 14 18 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. HLA-B*81:01/TL9 complex binds to T18A TCR with no conformational change. 2022 Frontiers in immunology Figure HIV T18A 33 37 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The rare docking mode of T18A CDR3beta on alpha2 helix of the HLA but not the peptide. 2022 Frontiers in immunology Figure HIV T18A 25 29 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The structure of T18A TCR/HLA-B*81:01/TL9 complex. 2022 Frontiers in immunology Figure HIV T18A 17 21 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The uncommon "opened" T18A CDR3alpha alters the relative orientation of Valpha to Vbeta. 2022 Frontiers in immunology Figure HIV T18A 22 26 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. (A) Test group: CL757-SS-infected TRIM5alphaTFP/TFP RMs with the appearance of a mutation, T146P, in all animals infected; except for H905, which has different escape mutations, I145V and T175I, located outside the major homology region (MHR, pink). 2022 Microbiology spectrum Figure HIV I145V;T146P;T175I 178;91;188 183;96;193 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. (C) Correction of Thr-146 to Pro restores viral kinetics and causes an increase in acute viral load in TRIM5alphaTFP/Q RMs compared to that in the reference group. 2022 Microbiology spectrum Figure HIV T146P 18 32 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. (C) First control group: CL757-WT-infected TRIM5alphaTFP/TFP RMs, with the T146P mutation appearing here as well. 2022 Microbiology spectrum Figure HIV T146P 75 80 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Also, the T146P mutation appears wherever the S37/S98 mutations were lost. 2022 Microbiology spectrum Figure HIV T146P 10 15 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. A The distance to the nearest centromere was calculated for all WT and K258R mutant integration sites from three independent experiments. 2022 Nature communications Figure HIV K258R 71 76 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Additional statistical analysis comparing the integration site pattern of WT and K258R mutant IN is shown in Table S1. 2022 Nature communications Figure HIV K258R 81 86 IN 94 96 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. C Fold change in K258R association with CENP-C over WT. 2022 Nature communications Figure HIV K258R 17 22 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Enrichment of K258R IN mutant HIV-1 in centromeres. 2022 Nature communications Figure HIV K258R 14 19 IN 20 22 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. HeLa cells were infected with virus generated from pNL4.3.Luc.R-E- carrying either WT or K258R mutant IN. 2022 Nature communications Figure HIV K258R 89 94 IN 102 104 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. HeLa cells were infected with WT and K258R for 16 h at MOI 10. 2022 Nature communications Figure HIV K258R 37 42 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. K258R mutant HIV-1 IN profoundly biases integration toward centromeres. 2022 Nature communications Figure HIV K258R 0 5 IN 19 21 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. K258R point mutation in HIV-1 IN has modest effects on early viral replication. 2022 Nature communications Figure HIV K258R 0 5 IN 30 32 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The K258R mutation in IN has minimal effect on integration site distribution into low-copy number sequences. 2022 Nature communications Figure HIV K258R 4 9 IN 22 24 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. The number of integrations falling in each bin was quantified and is shown as a count (WT in black, K258R in red). 2022 Nature communications Figure HIV K258R 100 105 35304442 A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Unique host sequences immediately flanking each integration by the K258R mutant IN were aligned to an alphoid repeat consensus sequence (AJ131208.1) using BLAST The consensus sequence was split into bins of two nucleotides and the number of integrations in each bin were counted. 2022 Nature communications Figure HIV K258R 67 72 IN 80 82 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. All these experiments were performed in duplicate c We compared infectivity expressed as RLU (relative units of luciferase) for WT, ESC (L592R mutation) and ESC + COM (L592R and K588R mutations) Env-EL9 sequences. 2022 Retrovirology Figure HIV K588R;L592R;L592R 178;137;168 183;143;174 Env 195 198 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Bars represent standard deviation from two experiments with three replicates per experiment d DOPE of the protein structure of the WT (black), WT with the escape mutation L592R (ESC, white) and WT with both escape and compensatory mutations (ESC + COM, dark gray). 2022 Retrovirology Figure HIV L592R 171 176 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. c Quantification of HIV-1 specific-CD8 + T cell responses (y axis) against DA9 (blue), Env-EL9 WT (green) and Env-EL9 with the L592R mutation (red), determined by the ELISpot analysis, at different time points (x axis). 2022 Retrovirology Figure HIV L592R 127 132 Env;Env 87;110 90;113 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. d Gag-DA9, Env-EL9 WT, Env-EL9 with L592R and Env-EL9 592R + 588R specific-CD8 + T-cell responses before and after LVC as the proportion of peptide specific IFN-gamma + production by CD8 + T-cells by multiparametric flow cytometry assay. 2022 Retrovirology Figure HIV L592R 36 41 Env;Env;Env;Gag 11;23;46;2 14;26;49;5 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. e The pie charts show the poly-functionality of Env-EL9 (upper pies) and Env-EL9 with L592R + L588R mutations (bottom pies) specific-CD8 + T-cell responses before (Jun-06) and after (Oct-15) LVC. 2022 Retrovirology Figure HIV L588R;L592R 94;86 99;91 Env;Env 48;73 51;76 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Note that in terms of protein stability, the order is the following: WT (more stable) > L592R with K588R > L592R (less stable). 2022 Retrovirology Figure HIV K588R;L592R;L592R 99;88;107 104;93;112 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Pseudoviruses were constructed from B2 c-11 with L592R mutation by site-directed mutagenesis. 2022 Retrovirology Figure HIV L592R 49 54 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Key sequence variants, C31S, R57S, and Q63E are shown within boxes. 2022 Frontiers in microbiology Figure HIV C31S;Q63E;R57S 23;39;29 27;43;33 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Furthermore, after development of the escape mutation, the reversion of methionine to w/t leucine at position 268 (M268L) only occurs after the reappearance of arginine at position 264. 2001 The Journal of experimental medicine Discussion HIV M268L 115 120 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In a fifth patient an alternative mutation (R264G) was seen. 2001 The Journal of experimental medicine Discussion HIV R264G 44 49 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. In subtype O viruses, and in some untyped viruses, R264K is a common variant; however, it is associated with other mutations such as V267I, K263R, and usually with D260E (Table ). 2001 The Journal of experimental medicine Discussion HIV D260E;K263R;R264K;V267I 164;140;51;133 169;145;56;138 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. It may also indicate that in vivo the mutation is only tolerable in subtype B viruses, all of which on the database have E260, when E260D and R264G mutations occur in the presence of L268. 2001 The Journal of experimental medicine Discussion HIV E260D;R264G 132;142 137;147 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Phylogenetic analysis suggests that although some of this recrudescence of w/t virus is derived from sequences laid down as provirus, other reversions arise de novo and do so in a manner where mutations occur in a certain order; that is, L268M appears to occur after reversion of K264R. 2001 The Journal of experimental medicine Discussion HIV K264R;L268M 280;238 285;243 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. R264G does not appear in the Los Alamos database. 2001 The Journal of experimental medicine Discussion HIV R264G 0 5 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. The observation that the R264G mutation can be tolerated by the laboratory-adapted LAI strain in vitro in the presence of E260 14 would argue that E260D is not an absolute requirement for the viability of R264G. 2001 The Journal of experimental medicine Discussion HIV E260D;R264G;R264G 147;25;205 152;30;210 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. The results presented here indicate that in subtype B viruses, if the R264K mutation is to be tolerated, a L268M mutation is preferred. 2001 The Journal of experimental medicine Discussion HIV L268M;R264K 107;70 112;75 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. We have described five HLA-B27 carrying HIV-infected patients, four of whom have acquired the same (R264K) escape mutation in gag. 2001 The Journal of experimental medicine Discussion HIV R264K 100 105 Gag 126 129 HIV infections 40 52 11157057 Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. We have shown that the R264K mutation is strongly associated with a second change L268M and that the acquisition of this doubly modified epitope does not appear to result from simple linkage between the mutations at sites 264 and 268. 2001 The Journal of experimental medicine Discussion HIV L268M;R264K 82;23 87;28 11737863 Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients. On the other hand, the identification of K70R, a zidovudine resistance mutation, and V82A, indinavir and ritonavir resistance mutation, probably confirm the detection of mutant(s) present in a low proportion and might explain the failure of sequence testing. 2001 BMC microbiology Discussion HIV K70R;V82A 41;85 45;89 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. A similar 10-fold hypersensitivity of Dbl mutant to RT8 appears to reflect the observation that the effect of N255D is dominant over that of N265D in the context of both mutations. 2005 AIDS research and therapy Discussion HIV N255D;N265D 110;141 115;146 RT 52 54 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. For example, the lack of change in sensitivity of N265D mutant to aptamer RT8 (Table 1) suggests that the residue N265 may not play a key role in binding to RT8. 2005 AIDS research and therapy Discussion HIV N265D 50 55 RT;RT 74;157 76;159 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. However, both E89G, which rarely occurs among clinical isolates as a primary mutation and the more commonly encountered K65R, both display a modest level of resistance to RT1t49 (3- to 5-fold). 2005 AIDS research and therapy Discussion HIV E89G;K65R 14;120 18;124 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. In addition, as shown by our earlier studies, both N255D and N265D mutations affected the DNA-dependent DNA polymerase processivity, while N255D was also defective for RNA-dependent DNA polymerase processivity. 2005 AIDS research and therapy Discussion HIV N255D;N255D;N265D 51;139;61 56;144;66 Pol;Pol 108;186 118;196 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. It is also interesting that N255D mutant displays a 10-fold hypersensitivity to RT8. 2005 AIDS research and therapy Discussion HIV N255D 28 33 RT 80 82 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. On the one hand, these results suggest that pre-existing NRTI-resistance mutations, due to altered affinities to template primer can confer co-resistance to aptamers or that mutations such as K65R could arise in response to aptamer therapy. 2005 AIDS research and therapy Discussion HIV K65R 192 196 NRTI 57 61 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Our previous work shows that changes in sensitivity to inhibition by aptamers for N255D and N265D mutant RTs directly correlate with their binding affinities to the aptamer. 2005 AIDS research and therapy Discussion HIV N255D;N265D 82;92 87;97 RT 105 108 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. Our results highlight several key features of the aptamer-resistant RTs bearing the mutations N255D, N265D or both (Dbl). 2005 AIDS research and therapy Discussion HIV N255D;N265D 94;101 99;106 RT 68 71 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. The above observation, however, was tempered by the fact that some of the NRTI-resistance mutations, such as E89G and K65R conferred a significant degree of resistance to RT1t49 (3 to 5-fold). 2005 AIDS research and therapy Discussion HIV E89G;K65R 109;118 113;122 NRTI 74 78 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. The K65R and E89G mutants have been reported to display reductions of 50% and 32% in their dissociation constants [,196,215]. 2005 AIDS research and therapy Discussion HIV E89G;K65R 13;4 17;8 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. The observation that N255D and N265D mutations confer resistance to aptamers in multiple classes suggests that these aptamers all bind HIV-1 RT in a similar manner. 2005 AIDS research and therapy Discussion HIV N255D;N265D 21;31 26;36 RT 141 143 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. The results of RT1t49 susceptibility testing (Table 3) with the ddI/ddC-resistant L74V, 3TC-resistant M184V and the AZT-resistant T215Y/M41L RTs are in agreement with our previously published efficacy tests using Jurkat T cell lines expressing each of the three selected anti-RT RNA aptamers, in which all the RNA aptamers were able to efficiently suppress replication of drug-resistant HIV. 2005 AIDS research and therapy Discussion HIV L74V;M184V;M41L;T215Y 82;102;136;130 86;107;140;135 RT;RT 141;276 144;278 16207371 HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors. We surmise that N255 residue may be involved in binding to RT8 - however, abrogation of this interaction by the N255D substitution may result in a conformational change in the RT8 or RT, which may lead to better interaction with another part of RT thus increasing its affinity to the mutant RT. 2005 AIDS research and therapy Discussion HIV N255D 112 117 RT;RT;RT;RT;RT 59;176;183;245;291 61;178;185;247;293 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. 2) Wiskerchen et al have reported that infection of MAGI cells with two other IN mutants K236A/K240A and K244A/E246A mutants, that are located in the same region as our KK240,4AE mutant, resulted in 0 and 4 beta-Gal positive cells, while infection of class I IN mutants produced 700 to 1400 beta-Gal positive cells. 2005 Retrovirology Discussion HIV E246A;K236A;K240A;K244A 111;89;95;105 116;94;100;110 IN;IN 78;259 80;261 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Also, in our infection experiments, a specific integration-defective class I mutant D64E virus was introduced in order to monitor the viral gene expression from unintegrated HIV-1 DNA species that are already translocated into nucleus during virus infection. 2005 Retrovirology Discussion HIV D64E 84 88 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Consistent with a previous study, infection with D64E mutant virus did not affect reverse transcription as compared to wt virus infection. 2005 Retrovirology Discussion HIV D64E 49 53 RT 82 103 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Consistently, a recent study by Lu et al also observed that infection of K215A/K219A mutant induced more than 3-fold lower luc activity compared to class I IN mutant D64N/D116N. 2005 Retrovirology Discussion HIV D116N;D64N;K215A;K219A 171;166;73;79 176;170;78;84 IN 156 158 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Consistently, their recent reports have shown that several IN mutants in same regions, including K215A/K219A, E244A and R262A/K264A, completely lost virus replication ability in CD4+ Jurkat T cells. 2005 Retrovirology Discussion HIV E244A;K215A;K219A;K264A;R262A 110;97;103;126;120 115;102;108;131;125 IN 59 61 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Even though these results were confirmed by Petit and colleagues by studying the intracellular localization of HIV-1 Flag-IN, other studies, using GFP-IN fusion protein, did not reveal the importance of K186Q and Q214/216L mutations for HIV-1 IN nuclear localization. 2005 Retrovirology Discussion HIV K186Q 203 208 IN;IN;IN 122;151;243 124;153;245 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Interestingly, our infection analysis revealed that more profound infection defects were found for all three IN C-terminal mutant viruses KK215,9AA, KK240,4AE and RK263,4AA than D64E mutant virus in Hela-CD4-CCR5-beta-Gal cells, dividing and non-dividing C8166 T cells. 2005 Retrovirology Discussion HIV D64E 178 182 IN 109 111 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Moreover, similar to our experimental system, their study revealed that, in the context of VSV-G pseudotyped virus infection in Jurkat cells, 2-LTR circle DNA levels of K215A/K219A and Q214L/Q216L were significantly lower than other mutants V165A and C130G, even though the inhibition of viral reverse transcription mediated by these mutants were comparable. 2005 Retrovirology Discussion HIV C130G;K215A;K219A;Q214L;Q216L;V165A 251;169;175;185;191;241 256;174;180;190;196;246 RT;LTR 294;144 315;147 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Previous work by Gallay et al., have proposed an atypical bipartite NLS (186KRK and 211KELQKQITK) in HIV-1 IN by finding that IN mutants K186Q and Q214/216L lost their karyophilic feature and their ability to bind to karyopherin alpha in vitro . 2005 Retrovirology Discussion HIV K186Q 137 142 IN;IN 107;126 109;128 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Results clearly show that the nuclear localization defective mutant KK215,9AA leads to significantly reduced levels of viral DNA in the nucleus, as compared to the wt and D64E viruses. 2005 Retrovirology Discussion HIV D64E 171 175 16232319 Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Second, infection experiments revealed that all three C-terminal mutant viruses (KK215,9AA, KK240,4AE and RK263,4AA) exhibited more severe defect of induction of beta-Gal positive cells and luc activity, as compared to an IN class 1 mutant D64E virus, in CD4+ HeLa-beta-Gal cells, dividing and non-dividing C8166 T cells. 2005 Retrovirology Discussion HIV D64E 240 244 IN 222 224 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. 'Long-range' effects of polymerase domain mutations such as F61Y and F61A are not without precedent and have been well documented. 2006 Nucleic acids research Discussion HIV F61A;F61Y 69;60 73;64 Pol 24 34 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Although F61W mutant displayed a similar proportion of consensus sequences (0.36 for F61W versus 0.39 for wild type), seven of 28 sequences (0.25) contained a unique U3 deletion and insertion of the PPT and flanking sequences (Figure 4). 2006 Nucleic acids research Discussion HIV F61W;F61W 9;85 13;89 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Although M184V mutant sequences were largely similar to those of wild type, the M184T mutant sequences included those with the insertion of tRNA in the 2-LTR junctions. 2006 Nucleic acids research Discussion HIV M184T;M184V 80;9 85;14 LTR 154 157 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Among the four F61 mutant viruses studied, the F61A mutant was the least infectious, replication-defective and produced the lowest level of viral DNA and no 2-LTR circles (Figure 3). 2006 Nucleic acids research Discussion HIV F61A 47 51 LTR 159 162 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. analyzed the 2-LTR circles from M184V and M184T mutant viruses. 2006 Nucleic acids research Discussion HIV M184T;M184V 42;32 47;37 LTR 15 18 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Despite using nested PCR, we failed to recover 2-LTR circle junctions from cells infected with F61A mutant virus, consistent with the absence of 2-LTR circles in the real-time PCR analysis (Figure 4). 2006 Nucleic acids research Discussion HIV F61A 95 99 LTR;LTR 49;147 52;150 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Experiments to measure virus spread showed that mutant viruses were defective in the order of wild-type>F61L>F61W>F61Y>=F61A. 2006 Nucleic acids research Discussion HIV F61A;F61L;F61W;F61Y 120;104;109;114 124;108;113;118 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. F61W RT displayed enhanced in vitro RT activity and processivity equivalent to wild-type RT, but exhibited the lowest in vitro strand displacement synthesis of all mutants studied (Table 1). 2006 Nucleic acids research Discussion HIV F61W 0 4 RT;RT;RT 5;36;89 7;38;91 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. F61Y RT displayed in vitro polymerase and strand displacement synthesis properties exceeding those of wild-type RT and near wild-type processivity on both RNA and DNA templates. 2006 Nucleic acids research Discussion HIV F61Y 0 4 Pol;RT;RT 27;5;112 37;7;114 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Furthermore, the results of the RNase H assays highlight the following features: (i) mutating a residue that contacts the template 5'-overhang can affect the activity of a distal domain such as RNase H with an active site located ~18 bp along the template-primer duplex; (ii) F61A RT is defective both in the efficiency and specificity of cleavage at the PPT/U3 RNA junction during generation of the PPT primer, while the ability to cleave at the PPT/U3 junction is abrogated. 2006 Nucleic acids research Discussion HIV F61A 274 280 RT 281 283 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In addition, the F61Y, F61L and F61A RTs exhibited lowered processivity (in that order) while F61W mutant RT displayed higher processivity compared with wild type. 2006 Nucleic acids research Discussion HIV F61A;F61L;F61W;F61Y 32;23;94;17 36;27;98;21 RT;RT 37;106 40;108 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In contrast, circle junction sequences were recovered with mutant F61Y, which also did not show any 2-LTR circles in that analysis. 2006 Nucleic acids research Discussion HIV F61Y 66 70 LTR 102 105 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. In fact, F61W appears to be similar to F61L in all respects except for its lowered strand displacement activity (Table 1). 2006 Nucleic acids research Discussion HIV F61L;F61W 39;9 43;13 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. None of the mutants tested (F61L, F61W, F61Y and F61A) showed specific defects in the assembly (Figure 1) or production of virion particles (data not shown). 2006 Nucleic acids research Discussion HIV F61A;F61L;F61W;F61Y 49;28;34;40 53;32;38;44 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. On the other hand, the F61L and F61Y mutant RTs had much higher strand displacement activity than wild-type RT in vitro. 2006 Nucleic acids research Discussion HIV F61L;F61Y 23;32 27;36 RT;RT 44;108 47;110 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Our results show that most F61 substitutions lead to defects in viral replication not only due to their effects on strand displacement, but also due to causes such as defects in elongation (F61L) and the efficiency and specificity of RNase H cleavages at the PPT (F61Y and F61A). 2006 Nucleic acids research Discussion HIV F61A;F61L;F61Y 273;190;264 277;194;269 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The distribution of 2-LTR circles formed by the F61L mutant virus was largely similar to that of wild-type, while that of F61W and F61Y mutant viruses differed. 2006 Nucleic acids research Discussion HIV F61L;F61W;F61Y 48;122;131 52;126;135 LTR 22 25 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The F61W mutant appears to suffer partly due to a strand displacement synthesis defect (as shown by greater U3 deletions and insertion of PPT sequences) since it appears equal in all other respects to F61L, which replicates much better. 2006 Nucleic acids research Discussion HIV F61L;F61W 201;4 205;8 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The fact that F61Y virus produced very few 2-LTR circles that could not be detected by real-time PCR suggests that the sequences recovered by nested PCR are amplification of a rare event or represent multiple, identical events. 2006 Nucleic acids research Discussion HIV F61Y 14 18 LTR 45 48 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The results of in vitro RNase H PPT-primer generation and primer removal assays showed that F61Y is indeed defective for PPT removal with one of lowest levels among F61 mutants (9% of wild type, Figure 5D and Table 1). 2006 Nucleic acids research Discussion HIV F61Y 92 96 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. The RNase H defect cumulatively with other in vitro defects, explains the rather severe defect of this mutant; and (iii) F61Y RT is mildly affected for PPT/U3 RNA cleavage, but shows reduced cleavage at PPT/U3 RNA-DNA junction, which correlates with virological results from the 2-LTR junction sequence analysis. 2006 Nucleic acids research Discussion HIV F61Y 119 125 LTR;RT 281;126 284;128 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. These results provided new insight into an additional defect of F61Y mutant that appears to have contributed to its severe replication defect. 2006 Nucleic acids research Discussion HIV F61Y 64 68 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. This is interesting considering the fact that F61L is less processive than F61W. 2006 Nucleic acids research Discussion HIV F61L;F61W 46;75 50;79 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. This suggested a defect in the RNase H function caused by the M184T mutation. 2006 Nucleic acids research Discussion HIV M184T 62 67 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Those studies showed that recombinant RTs with substitutions F61L, F61W and F61Y displayed wild type or higher levels of RNA-dependent DNA polymerase activity, while F61A RT displayed a decrease. 2006 Nucleic acids research Discussion HIV F61A;F61L;F61W;F61Y 166;61;67;76 170;65;71;80 Pol;RT;RT 139;38;171 149;41;173 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Though F61A RT had a near wild-type-like strand displacement activity, the processivity of this enzyme was severely reduced (Table 1). 2006 Nucleic acids research Discussion HIV F61A 7 11 RT 12 14 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Thus, impairment of intracellular viral DNA synthesis by the F61Y virus could not be explained by the in vitro behavior of polymerase activities of F61Y mutant RT. 2006 Nucleic acids research Discussion HIV F61Y;F61Y 61;148 65;152 Pol;RT 123;160 133;162 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Thus, it appears that despite the lowest processivity of all the mutants and a 5-fold reduction in one of the RNase H activities tested (PPT-primer removal) compared to wild type, the F61L virus displayed the highest replication capacity among the mutant viruses. 2006 Nucleic acids research Discussion HIV F61L 184 188 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Thus, it is understandable that despite a lower processivity of RT mutant F61L (Table 1), the generally more robust RT activity including strand displacement synthesis may support efficient elongation during viral DNA synthesis, permitting a basal virus replication and a minimally affected intracellular viral DNA synthesis. 2006 Nucleic acids research Discussion HIV F61L 74 78 RT;RT 64;116 66;118 16723431 Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function. Thus, the replication defect of F61A virus appeared to be a combination of lower enzymatic activity and processivity. 2006 Nucleic acids research Discussion HIV F61A 32 36 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. The aberrant properties of the I267A derivatives are consistent with such a model, in which the CTD normally plays a key role in aligning the viral DNA end for proper processing. 2006 Retrovirology Discussion HIV I267A 31 36 16790058 Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody. These proteins, I267A and I267A/I268A, exhibit both increased DNA binding affinity (Table 2), and an absence of the initial faster dissociation phase that is characteristic of the biphasic pattern normally observed with IN. 2006 Retrovirology Discussion HIV I267A;I267A;I268A 16;26;32 21;31;37 IN 220 222 16956392 HIV-2 Protease resistance defined in yeast cells. However, in our phenotyping system, the L99F substitution did not modify susceptibility either to LPV or to SQV. 2006 Retrovirology Discussion HIV L99F 40 44 16956392 HIV-2 Protease resistance defined in yeast cells. Moreover for the first time we were able to clearly define that the L90M substitution is responsible for SQV resistance but does not alter LPV sensitivity. 2006 Retrovirology Discussion HIV L90M 68 72 16956392 HIV-2 Protease resistance defined in yeast cells. The L99F substitution has previously been proposed to be involved in PI resistance, based on comparison of HIV-2 Protease sequences from PI untreated and treated patients. 2006 Retrovirology Discussion HIV L99F 4 8 PR;PI;PI 113;69;137 121;71;139 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. However, for the Vpr mutation, R77Q, a recent report has questioned its association with long-term nonprogressors. 2006 PLoS pathogens Discussion HIV R77Q 31 35 Vpr 17 20 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. Our results conclusively show that in our experimental paradigm, the proapoptotic potentials of Vpr(R77Q) and Vpr(I74A) are indistinguishable from that of Vpr(R77). 2006 PLoS pathogens Discussion HIV I74A;R77Q 114;100 118;104 Vpr;Vpr;Vpr 96;110;155 99;113;158 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. proposed that R77Q is associated with certain viral subtypes, such as subtype A, and not with disease progression. 2006 PLoS pathogens Discussion HIV R77Q 14 18 17140287 HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. would seem to indicate that the R77Q substitution has a moderate, positive effect on cell viability, and this effect may be related to viral replication efficiency rather than to proapoptotic signaling. 2006 PLoS pathogens Discussion HIV R77Q 32 36 17225856 Recruitment and activation of RSK2 by HIV-1 Tat. A Tat mutant (F38A) that does not bind RSK2 exhibited a transcriptional defect that cannot be attributed exclusively to RSK2. 2007 PloS one Discussion HIV F38A 14 18 Tat 2 5 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. Changes at the p1/p6 cleavage site (L449F or P453L), which on their own do not confer resistance, were associated with reduced sensitivity in the background of the I50V in protease. 2007 PLoS medicine Discussion HIV I50V;L449F;P453L 164;36;45 168;42;50 PR;Gag 172;18 180;20 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. The A431V substitution observed in our in vitro selection experiments has been described before, both in vitro and in vivo. 2007 PLoS medicine Discussion HIV A431V 4 9 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. The in vitro experiments that we have performed demonstrated the selection of NC/p1 cleavage site substitutions (A431V at the P2 position, and the K436E and I437V/T at the more distant P4' and P5' positions, respectively). 2007 PLoS medicine Discussion HIV A431V;I437T;I437V;K436E 113;157;157;147 119;164;164;152 NC 78 80 17227139 A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. This was structurally confirmed by the demonstration that wild-type protease can bind the wild-type NC/p1 cleavage site less well than the A431V-mutated cleavage site. 2007 PLoS medicine Discussion HIV A431V 139 144 PR;NC 68;100 76;102 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Alternatively, the fusion of Delta325 to eGFP may also aid A128T/E170G IN to preferentially bind to LEDGF/p75. 2007 PLoS pathogens Discussion HIV A128T;E170G 59;65 64;70 IN 71 73 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Detection of the IN mutations A128T and E170G at key positions after resistance selection provides in vivo confirmation for the previously reported structure. 2007 PLoS pathogens Discussion HIV A128T;E170G 30;40 35;45 IN 17 19 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Differential impact of the A128T/E170G mutation on interaction of recombinant IN with full-length LEDGF/p75 or the C-terminal fragment could not be documented in vitro by pull-down (Figure 5A) or AlphaScreen technology (unpublished data). 2007 PLoS pathogens Discussion HIV A128T;E170G 27;33 32;38 IN 78 80 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. In fact, poor replication of the double mutant virus in WT cells is rescued by overexpression of LEDGF/p75 (Figure S5B), corroborating that the A128T/E170 IN mutant virus still exploits LEDGF/p75 in vivo. 2007 PLoS pathogens Discussion HIV A128T 144 149 IN 155 157 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Moreover, replication of A128T/E170G virus was also severely impaired in the Jurkat p75- cells, which support normal replication of WT virus (Figure 7D). 2007 PLoS pathogens Discussion HIV A128T;E170G 25;31 30;36 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Replication of A128T/E170G virus in MT-4 cells overexpressing LEDGF/p75 truncation mutants suggests that its affinity for eGFP-Delta325 is more reduced than for LEDGF/p75, taking into account that eGFP-Delta325 is in excess of LEDGF/p75 (unpublished data). 2007 PLoS pathogens Discussion HIV A128T;E170G 15;21 20;26 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The fact that A128T/E170G IN displays a reduced affinity for full-length LEDGF/p75 seems to suggest at first sight that HIV can replicate without LEDGF/p75 perhaps using an alternative cofactor. 2007 PLoS pathogens Discussion HIV A128T;E170G 14;20 19;25 IN 26 28 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. The reduced replication kinetics of the mutated virus were further analyzed by quantitative PCR analysis of 293T cells infected with VSV-G pseudotyped A128T/E170G virus. 2007 PLoS pathogens Discussion HIV A128T;E170G 151;157 156;162 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Two mutations were detected in the IN coding region at key positions in the LEDGF/p75-IN interface (A128T and E170G) (Figure 1). 2007 PLoS pathogens Discussion HIV A128T;E170G 100;110 106;115 IN;IN 35;86 37;88 17397262 Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. Whereas the number of 2-LTR circles produced by WT virus increased more than 10-fold in the 293T eGFP-Delta325 cells (Figure S2E) as a result of the defect in integration (Figure S2F), the number of 2-LTR circles returned to almost normal levels when the cells were infected with A128T/E170G virus. 2007 PLoS pathogens Discussion HIV A128T;E170G 280;286 285;291 LTR;LTR 24;201 27;204 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. A recent report also demonstrated that both antiviral immune responses (induced by prior immunization) and short-term tenofovir administration were required to protect macaques against infection after intravenous inoculation with a high dose of a virulent K65R SIV isolate. 2007 Retrovirology Discussion HIV K65R 256 260 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Animal 30577 first had a rapid 47-fold reduction in viremia within 2 weeks of treatment but then had a 10-fold increase in viremia above nadir levels by 8 weeks of treatment, that was associated with the emergence of K70E followed by K65R viral mutants. 2007 Retrovirology Discussion HIV K65R;K70E 234;217 238;221 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. As discussed previously, it is unclear whether the need of continued tenofovir treatment to achieve optimal inhibition of K65R virus replication is due to residual direct antiviral activity of the tenofovir regimen against these mutants (e.g., in antigen-presenting cells), and/or to potential immunomodulatory effects of tenofovir (such as priming of IL-12 secretion) that promote the generation and maintenance of strong antiviral immune responses. 2007 Retrovirology Discussion HIV K65R 122 126 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Because a stable tenofovir treatment regimen was continued during the CD8+ cell depletion experiment, this dramatic increase in K65R viremia, which was associated with a reduction in CD4+ T lymphocyte counts, indicates that in the absence of CD8+ cells, tenofovir treatment alone had insufficient inhibitory activity against K65R RT-SHIV, and this virus had good replicative capacity and virulence. 2007 Retrovirology Discussion HIV K65R;K65R 128;325 132;329 RT 330 332 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Because the regimen of these HIV-1 infected persons included also other RT inhibitors (e.g., abacavir and lamivudine), the detection of K70E virus in macaques during tenofovir monotherapy is the first evidence that tenofovir can select directly for this K70E mutation in vivo. 2007 Retrovirology Discussion HIV K70E;K70E 136;254 140;258 RT 72 74 HIV infections 29 43 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Despite this important role of CD8+ cells, continued administration of tenofovir was still required to maintain maximal suppression of K65R viremia in animal 30577; in other words, both antiviral immune responses and tenofovir were needed. 2007 Retrovirology Discussion HIV K65R 135 139 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. For RT-SHIV infected animal 30577, the viral rebound following withdrawal of tenofovir therapy was relatively slow (in comparison to the more rapid and dramatic rebound during CD8+ cell depletion), and consisted of K65R in PBMC-associated infectious virus, but K70E in plasma viral RNA. 2007 Retrovirology Discussion HIV K65R;K70E 215;261 219;265 RT 4 6 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. In an in vitro assay that measures antibody-dependent cell-mediated virus inhibition, plasma samples of animal 30577 and of tenofovir-treated SIVmac251-infected animals that similarly suppressed K65R viremia to undetectable levels were found to have high antiviral activity in the presence of PBMC effector cells. 2007 Retrovirology Discussion HIV K65R 195 199 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. In the current macaque study, it is possible that a higher precursor mutation frequency at codon 70 (but still below the 0.2% detection limit in the baseline samples) may have predisposed for selective outgrowth of first variants with the K70E mutation which, in vitro, confers only a relatively minor fitness cost and minimal resistance to tenofovir (ranging from no effect to <= 2-fold reduced susceptibility). 2007 Retrovirology Discussion HIV K70E 239 243 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Many of these mutations have been described previously with or without K65R in HIV-1 infected persons receiving tenofovir-containing or other HAART regimens, and some (such as M41L) have been reported to contribute to a reduced virologic response to tenofovir when in combination with other RT mutations. 2007 Retrovirology Discussion HIV K65R;M41L 71;176 75;180 RT 291 293 HIV infections 79 93 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Similarly to observations with HIV-1, when K70E and K65R RT-SHIV mutants were both detected in plasma, these 2 mutations were found on separate viral genomes. 2007 Retrovirology Discussion HIV K65R;K70E 52;43 56;47 RT 57 59 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The CD8+ cell depletion experiment demonstrated that the reduced viremia in tenofovir-treated animal 30577 was mediated largely by CD8+ cells, because removal of CD8+ cells caused a transient ~1 million-fold increase of K65R viremia, to peak levels similar to those observed during acute viremia with wild-type RT-SHIV. 2007 Retrovirology Discussion HIV K65R 220 224 RT 311 313 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The clinical implications of the K70E and K65R RT-SHIV mutants were similar to those reported previously for K65R SIVmac251 mutants. 2007 Retrovirology Discussion HIV K65R;K65R;K70E 42;109;33 46;113;37 RT 47 49 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The current report provides further insights into the many aspects of chronic tenofovir therapy, including the sequential emergence and implications of K70E and K65R viral mutants. 2007 Retrovirology Discussion HIV K65R;K70E 161;152 165;156 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The demonstration of the direct causality between CD8+ cell-mediated immune responses and suppressed K65R viremia in tenofovir-treated animal 30577 is important, as it helps to explain observations in humans, where strong cell-mediated immune responses were associated with the maintenance of low-level viremia in HAART-treated individuals with drug-resistant HIV-1. 2007 Retrovirology Discussion HIV K65R 101 105 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The emergence of K65R RT-SHIV mutants during tenofovir treatment was accompanied by an accumulation of other RT mutations, believed to be compensatory mutations that improve the replicative capacity of K65R virus. 2007 Retrovirology Discussion HIV K65R;K65R 17;202 21;206 RT;RT 22;109 24;111 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The findings of a ~10-fold reduced viremia in most K65R RT-SHIV infected animals during continued tenofovir monotherapy are reminiscent of observations in people who are infected with M184V mutant HIV-1, and for whom continuation of lamivudine monotherapy is associated with a ~2- to 4-fold reduction in viremia and clinical benefits. 2007 Retrovirology Discussion HIV K65R;M184V 51;184 55;189 RT 56 58 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The K70E mutation has only been described in a few cases of tenofovir-treated HIV-1 infected persons, although it is possible that a more systematic investigation of early samples following tenofovir therapy may reveal a higher frequency. 2007 Retrovirology Discussion HIV K70E 4 8 HIV infections 78 92 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The K70E mutation has previously been described in HIV-1 after selection pressure with adefovir in vitro and in vivo . 2007 Retrovirology Discussion HIV K70E 4 8 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The K70E RT mutants were subsequently replaced by K65R RT mutants. 2007 Retrovirology Discussion HIV K65R;K70E 50;4 54;8 RT;RT 9;55 11;57 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. The present data largely confirm the observations made previously with tenofovir in the SIVmac251 model, but the use of RT-SHIV led to novel findings, such as the transient detection of K70E viral mutants early after the start of tenofovir therapy. 2007 Retrovirology Discussion HIV K70E 186 190 RT 120 122 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. These findings are consistent with observations in tenofovir-treated humans, where the detection of K65R is not always associated with a virologic rebound, and the detection of the K65R mutation with a virologic rebound was most likely in patients with high baseline RNA levels and low CD4+ cell counts. 2007 Retrovirology Discussion HIV K65R;K65R 100;181 104;185 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. These K70E mutants were then rapidly replaced by K65R mutants which in the absence of drug are more replication-impaired in vitro than K70E mutants, but in the presence of tenofovir could outgrow K70E mutants due to a slightly higher level (~4-5 fold) of in vitro resistance to tenofovir. 2007 Retrovirology Discussion HIV K65R;K70E;K70E;K70E 49;6;135;196 53;10;139;200 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. This is similar to previous observations in tenofovir-treated animals that were infected with K65R SIV mutants. 2007 Retrovirology Discussion HIV K65R 94 98 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. This lower viremia may be due to a combination of several factors, including decreased replicative capacity of the K65R mutants (especially of the early mutants, prior to the accumulation of presumed compensatory mutations), some residual antiviral effects of the tenofovir regimen, and/or antiviral immune responses (see further). 2007 Retrovirology Discussion HIV K65R 115 119 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. This replacement of variants based on replicative capacity would be similar to observations in lamivudine-treated patients, where differences in pre-therapy frequencies of codon 184 mutants also appear to explain the transient detection of M184I mutants, which are then replaced by the more fit M184V mutants. 2007 Retrovirology Discussion HIV M184I;M184V 240;295 245;300 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. This suggests that, at least when accompanied by other RT mutations, a potential attenuating effect of the K65R mutation on viral replicative capacity is by itself insufficient to explain the reduced viremia during tenofovir therapy. 2007 Retrovirology Discussion HIV K65R 107 111 RT 55 57 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Thus, our data suggest that further studies (including retrospective analysis of already available samples) are warranted to investigate the potential clinical benefits of continued tenofovir therapy in HIV-1 infected patients even after a partial rebound with the detection of K65R viral mutants, as it is possible that some individuals may eventually suppress viremia again. 2007 Retrovirology Discussion HIV K65R 278 282 HIV infections 203 217 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. When RT-SHIV infected macaques were started on tenofovir, there was a rapid selection for viral mutants with a K70E RT mutation. 2007 Retrovirology Discussion HIV K70E 111 115 RT;RT 5;116 7;118 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. While our macaque studies modeled only the responses to tenofovir monotherapy, such considerations may be even more relevant for HAART-treated humans, as the combination of the K65R mutation with some other drug-selected mutations can further decrease viral replication fitness and affect drug susceptibility (including restored susceptibility) to tenofovir or other drugs of the HAART regimen, which may offer additional opportunities for antiviral activity. 2007 Retrovirology Discussion HIV K65R 177 181 17417971 Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. While previous studies in macaques used usually higher tenofovir regimens (20-30 mg/kg subcutaneously SID), it is unclear if the 10 mg/kg tenofovir regimen of the current study may also have contributed to a transient outgrowth of K70E mutants that were subsequently, when intracellular drug levels built up to steady-state levels, replaced by the more resistant K65R mutants. 2007 Retrovirology Discussion HIV K65R;K70E 363;231 367;235 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. Protease covariation was dominated by the clustering of nelfinavir-associated mutations (D30N and N88D), two main groups of PI-resistance mutations associated either with V82A or L90M, and a newly identified cluster of the mutations V32I, L33F, I47V, I50V, I54L/M, and L76V. 2007 PLoS computational biology Discussion HIV D30N;I47V;I50V;I54L;I54M;L33F;L76V;L90M;N88D;V32I;V82A 89;245;251;257;257;239;269;179;98;233;171 94;249;255;263;263;243;273;183;102;237;175 PR;PI 0;124 8;126 17500586 HIV-1 subtype B protease and reverse transcriptase amino acid covariation. RT covariation was dominated by the distinct clustering of the TAMs and Q151M-associated mutations, and by the separation of the Type I and Type II TAMs. 2007 PLoS computational biology Discussion HIV Q151M 72 77 RT 0 2 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Additionally, they found no effect on the intracellular level of the CAp24 protein in H1299 cells transfected with the D51N mutant. 2007 Retrovirology Discussion HIV D51N 119 123 Capsid 69 71 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Furthermore, although our results demonstrated that the D51N and D51E substitutions could restore the in vitro tubular formation, the infectivity of all D51 mutation were rendered non-infectious indicating that this residue is indispensable. 2007 Retrovirology Discussion HIV D51E;D51N 65;56 69;60 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. However, intracellular concentrations of CAp24 protein in any of the cells transfected with D51N and D51Q were generally reduced. 2007 Retrovirology Discussion HIV D51N;D51Q 92;101 96;105 Capsid 41 43 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Importantly, despite the ability to form wild type-like viruses, the infectivity of D51E virions was significantly reduced, indicating the importance of optimal HIV-1 core stability. 2007 Retrovirology Discussion HIV D51E 84 88 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. In a recent study that was published after the present work was performed, Leschonsky et al described the two single amino acid substitution mutations, a D183E and D183N, in an infectious provirus clone HX10. 2007 Retrovirology Discussion HIV D183E;D183N 154;164 159;169 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. In contrast to our results, they found no effect on extracellular level of the CAp24 protein produced from H1299 cells transfected with the D183E mutant. 2007 Retrovirology Discussion HIV D183E 140 145 Capsid 79 81 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Only the D51E mutant particles were partially able to form immature- and mature-like viruses that resembled the wild type morphology. 2007 Retrovirology Discussion HIV D51E 9 13 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Remarkably, although no tubular structure was observed with the D51Q mutant by TEM analysis, an increased optical density measurement that reflects the assembly kinetics was repeatedly observed. 2007 Retrovirology Discussion HIV D51Q 64 68 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Structural and mutagenesis studies of D51A mutation in HIV-1 CAp24 has previously shown this invariable residue to be essential for tube formation in vitro, and for the replication and capsid formation in cultured virus. 2007 Retrovirology Discussion HIV D51A 38 42 Capsid;Capsid 185;61 191;63 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. The effects of D51 mutations on in vitro CAp24 assembly was monitored spectrophotometrically, and as expected, the assembly rate of both D51N and D51E mutants were substantially reduced relative to the wild type protein, although the ability of these mutants to form tubular structures was shown by thin-section transmission electron microscopy (TEM). 2007 Retrovirology Discussion HIV D51E;D51N 146;137 150;141 Capsid 41 43 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Thus, it seems likely that the D51N and D51E mutations impose less structural changes than the D51A mutation described earlier. 2007 Retrovirology Discussion HIV D51A;D51E;D51N 95;40;31 99;44;35 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. We here demonstrated that substitution of D51 with glutamate (D51E), asparagine (D51N), but not glutamine (D51Q) (three amino acids which in proteins have similar properties as aspartate; Glu > Asn > Gln) could partly restore in vitro CAp24 assembly but not the infectivity of the virus particles. 2007 Retrovirology Discussion HIV D51E;D51N;D51Q 62;81;107 66;85;111 Capsid 235 237 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Whereas no infectivity was observed with the D51N and D51Q virions, a subtle amount was seen with the D51E viruses in a single cell cycle infectivity assay. 2007 Retrovirology Discussion HIV D51E;D51N;D51Q 102;45;54 106;49;58 17903253 Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. With the two other non-infectious mutants, particles with aberrant core structures, either hollow-shaped spherical structures in endosomal vesicles (D51N) or particles with distorted core morphology (D51Q) were seen. 2007 Retrovirology Discussion HIV D51N;D51Q 149;200 153;204 18025130 A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. However, for a complete understanding of the biological effects of the KK10 WT and L6M peptides on DC function, it will be necessary to analyze how the KK10 WT form and its variants affect recognition of HLA-B2705 by the other myelomonocytic MHC class I receptors that have been described, including stimulatory receptors such as LIR6, which appears to have a particular capacity for recognizing HLA-B2705. 2007 The Journal of experimental medicine Discussion HIV L6M 83 86 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Based on the findings that Vpr is able to interact directly with some proteins of the NPC, including the nucleoporin hCG1, we have now identified two Vpr mutants, Vpr-L23F and -K27M, that are specifically deficient for hCG1-binding. 2007 Retrovirology Discussion HIV K27M;L23F 177;167 181;171 Vpr;Vpr;Vpr 27;150;163 30;153;166 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. However, targeting to the NE is not sufficient for the G2-arrest activity, since several Vpr point mutants with substitutions in the C-terminal basic region of the protein, such as Vpr-R90K and Vpr-R80A, have been reported as defective for the G2-arrest activity (present study and Refs.), while we show that both can still accumulate at the NE. 2007 Retrovirology Discussion HIV R80A;R90K 198;185 202;189 Vpr;Vpr;Vpr 89;181;194 92;184;197 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Like other Vpr mutants that fail to localize at the NE, such as Vpr-A30L and -F34I, both L23F and K27M substitutions affect the Vpr-induced G2-arrest and cell death. 2007 Retrovirology Discussion HIV A30L;F34I;K27M;L23F 68;78;98;89 72;82;102;93 Vpr;Vpr;Vpr 11;64;128 14;67;131 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. None of these modifications have been described previously for Vpr and our western blot analysis did not reveal any change in the level of expression and/or stability of the Vpr-K27M mutant compared to the wt protein. 2007 Retrovirology Discussion HIV K27M 178 182 Vpr;Vpr 63;174 66;177 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. The structural analysis confirms that the 3D structure and the stability of the three alpha-helices of Vpr are not significantly affected by the L23F and K27M substitutions, as indicated by the overall conservation of the hydrogen-bonding network of the protein. 2007 Retrovirology Discussion HIV K27M;L23F 154;145 158;149 Vpr 103 106 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. We can notice that the two other mutations, A30L and F34I, impairing the NE accumulation of Vpr involve amino acids located on the same face of the first alpha-helix of the protein (see on. 2007 Retrovirology Discussion HIV A30L;F34I 44;53 48;57 Vpr 92 95 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. While a previous study showed that virus expressing single-point mutants (Vpr-F34I and -H71R), which failed to concentrate at the NE, displayed decreased infectivity in macrophages, it was recently reported that a Vpr mutant with multiple substitutions, in which the 4 Leu residues, including Leu23, found within the first alpha-helix of the protein were replaced by Ala, failed to localize in the nucleus and rendered the virus unable to replicate in MDMs from two donors. 2007 Retrovirology Discussion HIV F34I;H71R 78;88 82;92 Vpr;Vpr 74;214 77;217 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. While substitutions of the Leu23 residue have been described previously, the mutation at position 27 (K27M) was not yet identified and is particularly interesting since the K27 is well-conserved among HIV-1 isolates and constitutes the only lysine residue along the whole Vpr sequence. 2007 Retrovirology Discussion HIV K27M 102 106 Vpr 272 275 18039376 Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. While the Vpr-L23F and -K27M mutant viruses displayed a wild-type level of replication in only one out of four donors, we cannot formally exclude that the replication defect observed in the three other donors may be related to the slight difference in the level of virion incorporation of the two Vpr mutants evidenced in. 2007 Retrovirology Discussion HIV K27M;L23F 24;14 28;18 Vpr;Vpr 10;297 13;300 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Additionally, bevirimat treatment had no effect on the processing of CA-SP1 in bevirimat-resistant SP1/A1V, as no uncleaved CA precursor (p25) was detected even at a concentration of 20 microM. 2007 PloS one Discussion HIV A1V 103 106 SP1;SP1;Capsid;Capsid 72;99;69;124 75;102;71;126 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Because drug resistance, and particularly cross-resistance, is a significant problem in antiretroviral therapy, it is notable that we were able to demonstrate that 3TC was highly effective against bevirimat-resistant SP1/A1V. 2007 PloS one Discussion HIV A1V 221 224 SP1 217 220 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Nevertheless, the fact that the SP1/A1V mutant is replication competent in this model does suggest that continued screening for this mutation in the clinical program is warranted. 2007 PloS one Discussion HIV A1V 36 39 SP1 32 35 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Our observation that protease-inhibitor resistant NL4-3 PRI54V+V82A with impaired CA-SP1 cleavage is hypersensitive to bevirimat activity represents a unique form of antiviral synergy in which a drug-resistant enzyme inefficiently cleaves the same site where a drug exerts its antiviral activity. 2007 PloS one Discussion HIV V82A 63 67 PR;SP1;Capsid;PR 21;85;82;56 29;88;84;58 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Replication of HIV-1 PRI54V+V82A occurs reproducibly in PHA-activated PBMCs, so in vitro antiviral assays were performed with these cells. 2007 PloS one Discussion HIV V82A 28 32 PR 21 23 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. Single mutations in reverse transcriptase (RT) confer resistance to nucleoside RT inhibitors (M184V, K65R) and nonnucleoside RT inhibitors (Y181C) without significantly compromising viral fitness, yet these drugs are used in most antiretroviral regimens. 2007 PloS one Discussion HIV K65R;M184V;Y181C 101;94;140 105;99;145 RT;RT;RT;RT 20;43;79;125 41;45;81;127 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. This observation has important clinical relevance because it might be predicted that patients with protease-inhibitor resistance mutations that impair CA-SP1 cleavage (such as PRI54V+V82A) might respond to bevirimat treatment with greater viral load reductions than drug-naive patients with WT HIV-1. 2007 PloS one Discussion HIV V82A 183 187 PR;SP1;Capsid;PR 99;154;151;176 107;157;153;178 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. This suggests that there may be selective pressure to maintain this sequence in HIV-1-infected humans, and de novo generation of the SP1/A1V mutant may not readily occur. 2007 PloS one Discussion HIV A1V 137 140 SP1 133 136 HIV infections 80 94 18043758 Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. While the SP1/A1V mutant was shown to be replication competent in this model, it should be noted that the amino acid sequence at the CA-SP1 cleavage junction, including the alanine at position one of SP1, is highly conserved among different HIV-1 strains and to our knowledge no naturally occurring polymorphisms have been reported at this residue. 2007 PloS one Discussion HIV A1V 14 17 SP1;SP1;SP1;Capsid 10;136;200;133 13;139;203;135 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. A recent study also demonstrates the presence of N348I in RT sequences from over 3,000 treated individuals with subtype B HIV-1 in a UK database. 2007 PLoS medicine Discussion HIV N348I 49 54 RT 58 60 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Additional studies also demonstrate that Q145M significantly decreases viral replication capacity and that the recombinant enzyme displays a large loss in catalytic efficiency. 2007 PLoS medicine Discussion HIV Q145M 41 46 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Apart from Q145M, which has been reported to confer broad resistance to several NRTIs and NNRTIs, and Y181C/I, which may confer resistance to stavudine in addition to NVP, N348I represents the only other example of an in vivo mutation that confers decreased susceptibility to two classes of RT inhibitors. 2007 PLoS medicine Discussion HIV N348I;Q145M;Y181C;Y181I 172;11;102;102 177;16;109;109 NNRTI;NRTI;RT 90;80;291 96;85;293 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. As expected with HIV, there was a strong codon bias, with most of the mutant N348I (98.6%) encoded by ATT, while more than 97% of WT N348 was encoded by AAT. 2007 PLoS medicine Discussion HIV N348I 77 82 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Biochemical analyses designed to elucidate the mechanism by which N348I confers AZT resistance indicate that this mutation, consistent with other TAMs, acts by an excision rather than discrimination phenotype. 2007 PLoS medicine Discussion HIV N348I 66 71 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Consistent with our cell culture-based assays, NNRTI resistance was also observed at the enzyme level with recombinant RT expressing N348I. 2007 PLoS medicine Discussion HIV N348I 133 138 NNRTI;RT 47;119 52;121 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. For example, the M41L mutation has been reported to confer between 1.4- to 4-fold AZT resistance, the K70R mutation up to 8-fold resistance, and T215Y up to 16-fold resistance. 2007 PLoS medicine Discussion HIV K70R;M41L;T215Y 102;17;145 106;21;150 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Furthermore, other groups have also recently demonstrated that the N348I mutation confers both AZT and NNRTI resistance; with the Monogram group reporting a 2.4-fold change in AZT susceptibility, while another group reported a 23-fold change in AZT susceptibility. 2007 PLoS medicine Discussion HIV N348I 67 72 NNRTI 103 108 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Furthermore, the N348I mutation is associated with M184V/I, TAMs, K103N and Y181C and is selected by NVP and AZT treatment. 2007 PLoS medicine Discussion HIV K103N;M184I;M184V;N348I;Y181C 66;51;51;17;76 71;58;58;22;81 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Furthermore, the phenotypic findings are consistent with our clinical data demonstrating the significant association of N348I with TAMs and NNRTI mutations and its selection in patients on AZT and NVP combination therapy. 2007 PLoS medicine Discussion HIV N348I 120 125 NNRTI 140 145 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, in contrast to N348I, the prevalence of Q145M in an Italian cohort of 3,595 patients was lower (2.36%) and was always found in the presence of key drug resistance mutations. 2007 PLoS medicine Discussion HIV N348I;Q145M 24;49 29;54 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, this can be explained by several possibilities, including that M184V/I and N348I are not genetically linked, that their coincident emergence is due to a high proportion of the Centre's cohort being prescribed 3TC, or that N348I has an effect on M184V/I that is independent of decreasing drug susceptibility such as altering viral fitness. 2007 PLoS medicine Discussion HIV M184I;M184I;M184V;M184V;N348I;N348I 72;254;72;254;84;231 79;261;79;261;89;236 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In addition, a recent study demonstrated that reversion of N348I to the WT codon in an RT gene from an isolate derived from an RTI-experienced patient increased AZT sensitivity 5- to 10-fold. 2007 PLoS medicine Discussion HIV N348I 59 64 RT;RT 127;87 130;89 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In conclusion, we have demonstrated that a mutation in the connection domain of the HIV-1 RT, N348I, is prevalent in drug-treated individuals, appears relatively early in drug therapy, and confers decreased susceptibility to AZT and NNRTIs. 2007 PLoS medicine Discussion HIV N348I 94 99 NNRTI;RT 233;90 239;92 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In contrast, N348I does not make direct contacts with the T/P. 2007 PLoS medicine Discussion HIV N348I 13 18 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In our cohort N348I was associated with the appearance of K103N, V108l, Y181C/I, and G190A/S early in virological failure (Figure 2) and was significantly associated with these mutations in analysis of the entire database (Figure 1). 2007 PLoS medicine Discussion HIV G190A;G190S;K103N;N348I;Y181C;Y181I 85;85;58;14;72;72 92;92;63;19;79;79 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In our cohort, Q145M was exceedingly rare with a prevalence of less than 0.5%. 2007 PLoS medicine Discussion HIV Q145M 15 20 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In this regard, N348I, alone or in combination with TAMs, conferred 2- to 4-fold AZT resistance. 2007 PLoS medicine Discussion HIV N348I 16 21 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In this regard, our analyses confirm that the N348I mutation, alone and in combination with TAMs, decreases the enzyme's RNase H activity. 2007 PLoS medicine Discussion HIV N348I 46 51 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In this regard, our analysis ranks N348I as the ninth most prevalent resistance mutation from a total of 39 different RT codons that were evaluated in RTI experienced patients and this mutation was observed more frequently in our cohort than mutations at codons 210, 69, 44, 190, 118, and 74, most of which have been the topic of multiple clinical, genetic, virological, biochemical and structural analyses. 2007 PLoS medicine Discussion HIV N348I 35 40 RT;RT 151;118 154;120 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. In this study, we demonstrate a role of the commonly selected N348I mutation in the connection domain of HIV-1 RT in both NRTI (AZT) and NNRTI (NVP and EFV) resistance. 2007 PLoS medicine Discussion HIV N348I 62 67 NNRTI;NRTI;RT 137;122;111 142;126;113 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Interestingly, N348 in p66 lies in close proximity to I270 and P272 at the base of the thumb domain in some crystal structures, suggesting a possible mechanism by which N348I mediates AZT resistance. 2007 PLoS medicine Discussion HIV N348I 169 174 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Interestingly, N348I also conferred decreased susceptibility to EFV and NVP, data that are also consistent with studies from other groups. 2007 PLoS medicine Discussion HIV N348I 15 20 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. It is curious that our data demonstrate a strong association of N348I with M184V/I despite it having little effect on drug susceptibility in the context of M184V. 2007 PLoS medicine Discussion HIV M184I;M184V;M184V;N348I 75;75;156;64 82;82;161;69 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I conferred a small increase in 3TC resistance in the context of TAMs but did not counteract the previously observed antagonism between M184V and TAMs. 2007 PLoS medicine Discussion HIV M184V;N348I 140;0 145;5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I is more prevalent in clinical samples from patients treated with RTIs compared with samples from treatment-naive individuals. 2007 PLoS medicine Discussion HIV N348I 0 5 RT 71 75 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I significantly potentiated EFV and NVP resistance when combined with K103N. 2007 PLoS medicine Discussion HIV K103N;N348I 74;0 79;5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. N348I was also significantly associated with M184V/I in our cohort. 2007 PLoS medicine Discussion HIV M184I;M184V;N348I 45;45;0 52;52;5 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Nevertheless, additional biochemical and structural studies are warranted to define the exact mechanism by which N348I confers RTI resistance. 2007 PLoS medicine Discussion HIV N348I 113 118 RT 127 130 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Notably, N348I was the first mutation observed in two patients in our cohort. 2007 PLoS medicine Discussion HIV N348I 9 14 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. One of the major limitations of this study is that while the data demonstrate that the appearance of N348I is associated with an increase in viral load, which is at least as large as the recognised TAMs, it does not account for the simultaneous appearance of other key PI or RT drug resistance mutations that could also contribute to the observed increase in viral load. 2007 PLoS medicine Discussion HIV N348I 101 106 PI;RT 269;275 271;277 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Taken together, our data underscore the important role of N348I in conferring drug resistance to AZT and NNRTIs. 2007 PLoS medicine Discussion HIV N348I 58 63 NNRTI 105 111 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The early appearance of N348I after initiation of antiretroviral therapy is consistent with it playing a key role in the development of RTI resistance rather than being an accessory mutation that appears after primary mutations. 2007 PLoS medicine Discussion HIV N348I 24 29 RT 136 139 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The frequency of N348I in the first and second datasets was 13.6% and 13.0%, respectively. 2007 PLoS medicine Discussion HIV N348I 17 22 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The high prevalence of N348I is not unique to the Centre's database as it was also identified in a separate analysis of mutations beyond RT codon 240 in a large US clinical database (Quest Diagnostics). 2007 PLoS medicine Discussion HIV N348I 23 28 RT 137 139 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The level of AZT resistance conferred by N348I alone is comparable to the levels of resistance conferred by other individual TAMs. 2007 PLoS medicine Discussion HIV N348I 41 46 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The mechanism of AZT resistance can be ascribed to increased nucleotide excision, as observed from an RNA/DNA T/P, and is likely to be manifested through decreased RNase H activity conferred by N348I. 2007 PLoS medicine Discussion HIV N348I 194 199 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The N348I mutation also appears relatively early in virological failure, generally before the appearance of TAMs and usually at the same time as the acquisition of NNRTI resistance mutations. 2007 PLoS medicine Discussion HIV N348I 4 9 NNRTI 164 169 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. The structural mechanism by which N348I confers AZT (and NNRTI) resistance, however, cannot be inferred from this study. 2007 PLoS medicine Discussion HIV N348I 34 39 NNRTI 57 62 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. This is in contrast to another connection domain mutation, G333D/E, which is associated with dual resistance to AZT and 3TC. 2007 PLoS medicine Discussion HIV G333D;G333E 59;59 66;66 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Thus, the decrease in the formation of this cleavage product is significant and suggests a possible mechanism by which N348I confers AZT resistance. 2007 PLoS medicine Discussion HIV N348I 119 124 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. Thus, the prevalence of N348I in three large databases indicates that this mutation is likely to be present in other clade B cohorts receiving antiretroviral therapy. 2007 PLoS medicine Discussion HIV N348I 24 29 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. To delineate the role of N348I in RTI resistance, this mutation was introduced into molecular HIV-1 clones with defined genetic backbones. 2007 PLoS medicine Discussion HIV N348I 25 30 RT 34 37 18052601 N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. While the effect of N348I on viral replication fitness has not been established, recombinant enzymes harbouring this mutation facilitate DNA synthesis reactions at least as efficiently as the WT enzyme (unpublished data). 2007 PLoS medicine Discussion HIV N348I 20 25 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. For HIV-1 RT it was concluded from biochemical and structural data that the exchange of T215 to an aromatic residue (T215F/Y) enhances binding of ATP, but not PPi, thus facilitating excision. 2008 Nucleic acids research Discussion HIV T215F;T215Y 117;117 124;124 RT 10 12 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. The mutations involved in the enhanced excision of AZTMP in HIV-1 RT are M41L, D67N, K70R, T215Y/F and K219Q/E (Figure 7). 2008 Nucleic acids research Discussion HIV D67N;K219E;K219Q;K70R;M41L;T215F;T215Y 79;103;103;85;73;91;91 83;110;110;89;77;98;98 RT 66 68 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. This result indicates that the mutation I224T is important for viral fitness since it can reconstitute the polymerization activity of mt4 in SFVmac-infected cells. 2008 Nucleic acids research Discussion HIV I224T 40 45 18096624 AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. While mt3 also shows a reduced value for vmax, the I224T mutation of mt4 is obviously responsible for an increase of vmax similar to that of the WT levels (Table 2), implying that if saturating dNTP concentrations are present in infected cells, reverse transcription will not be greatly impaired in SFVmac viruses harboring mt4. 2008 Nucleic acids research Discussion HIV I224T 51 56 RT 245 266 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. All patients with apparently monophyletic L90M origins were sampled <=3 times. 2008 Retrovirology Discussion HIV L90M 42 46 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Evidence was obtained that in a substantial subset of patients (5/15) the L90M mutations were selected on multiple occasions. 2008 Retrovirology Discussion HIV L90M 74 78 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. Four out of five of the subjects with multiple L90M origins four were sampled at >=4 time points (the fifth patient 6501 was sampled twice). 2008 Retrovirology Discussion HIV L90M 47 51 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. In another subset of patients our analysis indicated that the later dominant L90M variants descended from the earlier minority L90M variant in a manner consistent with step-wise drug resistance mutations gradually accumulating on descendents of the original L90M virus. 2008 Retrovirology Discussion HIV L90M;L90M;L90M 77;127;258 81;131;262 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. In order to further investigate this phenomenon we selectively amplified and then sequenced HIV variants carrying the frequently detected protease inhibitor resistance mutations L90M when these viruses were still only present as minority variants. 2008 Retrovirology Discussion HIV L90M 178 182 PR 138 146 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The detection of a polyclonal origin for the commonly selected L90M protease mutation was anticipated given the constant generation of HIV mutants. 2008 Retrovirology Discussion HIV L90M 63 67 PR 68 76 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. The L90M variant that eventually emerged to readily detectable levels. 2008 Retrovirology Discussion HIV L90M 4 8 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. using direct PCR population sequencing) could therefore be of different origin than the earlier replicating minority L90M viruses. 2008 Retrovirology Discussion HIV L90M 117 121 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. We then compared these viruses with the L90M viruses from the same patients that later came to dominate their plasma quasispecies. 2008 Retrovirology Discussion HIV L90M 40 44 18221530 Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients. While the phylogenetic analysis was able to differentiate between monophyletic or multiple origins of the L90M variants in many of the patients, it appeared most powerful when multiple sequences were available from several time points. 2008 Retrovirology Discussion HIV L90M 106 110 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. 3TC and NNRTIs have been shown to select respectively for changes such as M184V and Y181C that resensitize TAM-containing HIV-1 RT to Zidovudine by decreasing the excision of this drug. 2008 Retrovirology Discussion HIV M184V;Y181C 74;84 79;89 NNRTI;RT 8;128 14;130 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Although both mutations are located in close vicinity to the M41L residue, the structural basis for resistance to Zidovudine for the latter mutation itself is not obvious. 2008 Retrovirology Discussion HIV M41L 61 65 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Considering the much lower prevalence of E40F compared to K43E, the selection of the latter mutation can not be explained solely in terms of compensation for the E40F change. 2008 Retrovirology Discussion HIV E40F;E40F;K43E 41;162;58 45;166;62 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. For instance, mutations at codons 44 and 118 associated with dual resistance to Zidovudine and 3TC are much more common than E40F. 2008 Retrovirology Discussion HIV E40F 125 129 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. have demonstrated that the frequency of K43E correlated with the number of previously received NRTI. 2008 Retrovirology Discussion HIV K43E 40 44 NRTI 95 99 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. In conclusion, our results suggest that an RC-compensating mutation (K43E) could have an additional effect on CTL escape. 2008 Retrovirology Discussion HIV K43E 69 73 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. In contrast, the appearance of the K43E change can be explained mainly by effects on the replicative capacity. 2008 Retrovirology Discussion HIV K43E 35 39 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. In this study we show that these E40F and K43E changes are highly associated with mutations from the TAM-1 pathway (M41L, L210W and T215Y) and less with the amino acid changes from the TAM-2 pathway (D67N, K70R, T215F and K219Q/E) (Table 2). 2008 Retrovirology Discussion HIV D67N;E40F;K219E;K219Q;K43E;K70R;L210W;M41L;T215F;T215Y 200;33;222;222;42;206;122;116;212;132 204;37;229;229;46;210;127;120;217;137 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Predictions using Netchop, a neural network based prediction method, suggested that addition of the K43E change in the background of M41L reduces the chance of proteasomal cleavage. 2008 Retrovirology Discussion HIV K43E;M41L 100;133 104;137 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Rather M41L may have a more indirect effect on ATP binding perhaps via alteration of van der Waals contacts with F116, itself a site of a resistance mutation as well as being adjacent to the nucleotide interacting residue Y115. 2008 Retrovirology Discussion HIV M41L 7 11 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Selection of the E40F change is driven by an increase in resistance to Zidovudine (nine to fourteen-fold). 2008 Retrovirology Discussion HIV E40F 17 21 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Several reports have shown that selection of the M41L change makes the epitope ALVEICTEM(EK) (amino acid 33 to 41/43) more immunogenic. 2008 Retrovirology Discussion HIV M41L 49 53 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The association of K43E with changes at these codons or H208Y, K219N/R and V75M changes may potentially involve a compensatory interaction, but further studies will be necessary to investigate this relationship. 2008 Retrovirology Discussion HIV H208Y;K219N;K219R;K43E;V75M 56;63;63;19;75 61;70;70;23;79 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The E40F and K43E changes belong to a growing list of newly identified mutations that are associated with primary NRTI-resistance. 2008 Retrovirology Discussion HIV E40F;K43E 4;13 8;17 NRTI 114 118 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The observation that the E40F and K43E substitutions are highly associated with TAM-1 changes, suggests that the biochemical mechanism of action is most likely an interaction with these changes. 2008 Retrovirology Discussion HIV E40F;K43E 25;34 29;38 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. The resulting effect on CTL escape might positively influence the selection of the K43E change in patients with specific HLA-types. 2008 Retrovirology Discussion HIV K43E 83 87 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. This nicely confirms the previous described association of K43E, K43N and K43Q with some TAM-1 mutations. 2008 Retrovirology Discussion HIV K43E;K43N;K43Q 59;65;74 63;69;78 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. To unravel the specific roles of the E40F and K43E we investigated their effect on drug susceptibility and replication by studying recombinant viral isolates as well as site directed mutants. 2008 Retrovirology Discussion HIV E40F;K43E 37;46 41;50 18271957 Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. We hypothesized that the K43E change may (partially) compensate for this increased immunogenicity. 2008 Retrovirology Discussion HIV K43E 25 29 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). C12L, A44R and B7R all carry MVA-specific mutations that do not occur in any other sequenced strain of Vaccinia virus. 2008 PloS one Discussion HIV A44R;C12L 6;0 10;4 18286194 Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). Indeed, poxviruses appear to have taken a grapeshot-like approach to disruption of the TLR/IL-1R signalling pathway, though MVA's gun has been spiked by deletion of many components, including A52R, which like A46R can inhibit NF-kappaB activation, albeit by a distinct subset of stimuli. 2008 PloS one Discussion HIV A46R;A52R 209;192 213;196 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. A360V appears to compensate for the deficit introduced by TAMs, which helps to explain why this mutation is generally detected late following the emergence of classic TAMs. 2008 The Journal of biological chemistry Discussion HIV A360V 0 5 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Accordingly, in contrast to TAMs, which only show increased excision when ATP is the PPi donor, the addition of A360V and/or N348I against a background of TAMs increases the efficiency of AZT-MP excision with both PPi and ATP. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 112;125 117;130 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Binding in the polymerase-competent mode is either not further affected with enzymes containing N348I or modestly enhanced with enzymes containing A360V. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 147;96 152;101 Pol 15 25 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Clinical data obtained from Canadian (this study) and Brazilian cohorts suggest that N348I can appear early in therapy, independently of preselected TAMs, whereas A360V appears late following the emergence of TAMs. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 163;85 168;90 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Connection domain mutations N348I and A360V in HIV-1 RT can contribute to increases in AZT resistance. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 38;28 43;33 RT 53 55 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. However, the selective diminution in substrate binding in RNase H-competent complexes suggests a possible role for N348I in p51, which is found within 16 A between positions -15 and -16 of the primer. 2008 The Journal of biological chemistry Discussion HIV N348I 115 120 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. In contrast, N348I does not appear to exert its effects through differences in nucleic acid binding. 2008 The Journal of biological chemistry Discussion HIV N348I 13 18 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Increases in processive DNA synthesis associated with TAMs/A360V and TAMs/N348I appear to account for this effect. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 59;74 64;79 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. N348I shows the strongest effects in this regard. 2008 The Journal of biological chemistry Discussion HIV N348I 0 5 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. RNase H-independent Contribution to Excision:Despite the mechanistic link between diminished RNase H cleavage and increases in excision, our results point to an additional, RNase H-independent contribution to AZT resistance by N348I and A360V. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 237;227 242;232 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Structural Interpretation:The aforementioned results raise the question of how the two connection mutations N348I and A360V affect specifically the RNase H-competent complex. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 118;108 123;113 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Substrate binding follows the order WT RT > TAMs > TAMs/A360V > TAMs/N348I > TAMs/A360V/N348I, which correlates directly with RNase H activity measurements in time course experiments. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I;A360V;N348I 82;88;56;69 87;93;61;74 RT 39 41 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Subtle increases in substrate binding with A360V may be attributable to additional contacts with the longer side chain. 2008 The Journal of biological chemistry Discussion HIV A360V 43 48 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The bulkier side chain of A360V may therefore influence the proper positioning of the primer to the RNase H active site. 2008 The Journal of biological chemistry Discussion HIV A360V 26 31 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The moderate increases in binding in the polymerase-competent mode with A360V provide a plausible mechanism that can translate into both increases in excision and the ensuing rescue reaction. 2008 The Journal of biological chemistry Discussion HIV A360V 72 77 Pol 41 51 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The TAMs/A360V/N348I mutant is still more efficient in AZT-MP excision and rescue of DNA synthesis as compared with TAMs when both enzymes contain the RNase H-negative E478Q mutation. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I;E478Q 9;15;168 14;20;173 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. The TAMs/A360V/N348I mutant that is severely compromised in RNase H activity delays the release of the primer. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 9;15 14;20 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. This effect is amplified as the nucleic acid substrates get shorter, which helps to explain why transiently formed hybrids become detectable with the TAMs/A360V/N348I mutant. 2008 The Journal of biological chemistry Discussion HIV A360V;N348I 155;161 160;166 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. This is seen in the presence and absence of TAMs, which helps to explain why N348I often emerges early after initiation of therapy before the selection of classic TAMs. 2008 The Journal of biological chemistry Discussion HIV N348I 77 82 18547911 Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms. Thus, the N348I mutation in p66 may affect substrate binding indirectly. 2008 The Journal of biological chemistry Discussion HIV N348I 10 15 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. At 6 months, the proportion of women with K103N detected by LigAmp was also similar in SD NVP-naive versus SD NVP-experienced women. 2008 The Journal of infectious diseases Discussion HIV K103N 42 47 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. At 6 weeks, the proportion of SD NVP-experienced women with K103N detected by LigAmp (45.5%), was nearly identical to the proportion of SD NVP-naive women with K103N detected by the same method in this study (45.6%) and in the HIVNET 012 trial (47.1%). 2008 The Journal of infectious diseases Discussion HIV K103N;K103N 60;160 65;165 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. However, our retrospective study of the HIVNET 012 cohort found no difference in detection of K103N in women by 2 years after first versus subsequent SD NVP use. 2008 The Journal of infectious diseases Discussion HIV K103N 94 99 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. The median %K103N was slightly higher at 6 weeks and 6 months in the SD NVP-experienced group, but these differences were not statistically significant. 2008 The Journal of infectious diseases Discussion HIV K103N 12 17 18582198 Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. We did observe a trend toward increased detection of K103N at 12 months in the NVP-experienced group. 2008 The Journal of infectious diseases Discussion HIV K103N 53 58 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Analyzing proviral DNA synthesis, S149A was found altered at the level of first-strand transfer DNA and subsequent steps that resulted in abolition of 2-LTR formation. 2008 Retrovirology Discussion HIV S149A 34 39 LTR 153 156 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Considering the S178A mutant, stability impairment may be deleterious for steps lying between the final RT and integration. 2008 Retrovirology Discussion HIV S178A 16 21 RT 104 106 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Electron microscopy analyses and biochemical experiments did not reveal any morphological or maturation defect in the S178A mutant. 2008 Retrovirology Discussion HIV S178A 118 123 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Furthermore, S109A substitution was found to dramatically impair Gag precursor processing and in vivo core assembly. 2008 Retrovirology Discussion HIV S109A 13 18 Gag 65 68 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Furthermore, VSV-G pseudotyping was found to enhance efficiency of late RT in cells infected with the S149A mutant. 2008 Retrovirology Discussion HIV S149A 102 107 RT 72 74 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Here, we found that VSV-G incorporation restores infectivity of S149A and S178A mutants. 2008 Retrovirology Discussion HIV S149A;S178A 64;74 69;79 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In contrast, the restoration of infectious properties was not observed for S109A virions pseudotyped with VSV-G. 2008 Retrovirology Discussion HIV S109A 75 80 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. In this context, core defects reported herein for S149A and S178A mutants may affect the capacity of the viral reverse transcription complex to relocalize to an appropriate site in the host cell cytoplasm. 2008 Retrovirology Discussion HIV S149A;S178A 50;60 55;65 RT 111 132 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Indeed, VSV-G-S149A and VSV-G-S178A efficiently supported RT and 2-LTR circle formation. 2008 Retrovirology Discussion HIV S149A;S178A 14;30 19;35 LTR;RT 67;58 70;60 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Interestingly, S149A and S178A mutants were not or poorly rescued by incorporation of MLV Env that triggers the viral core into the host cell cytoplasm by fusion at the plasma membrane. 2008 Retrovirology Discussion HIV S149A;S178A 15;25 20;30 Env 90 93 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Moreover, the corresponding envelope stripped cores dissociated in vitro more rapidly than WT cores, indicating that the loss of infectivity and post-entry blocks observed for the S178A mutant correlate to modifications in in vitro core stability. 2008 Retrovirology Discussion HIV S178A 180 185 Env 28 36 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Proviral DNA analysis revealed that the S178A mutant was only slightly affected in synthesis of the different DNA intermediates checked. 2008 Retrovirology Discussion HIV S178A 40 45 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. stating that assembled cores may be purified from S109A mutated viruses. 2008 Retrovirology Discussion HIV S109A 50 55 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. The ability of S178A and S149A cores to traffic into the target cell after viral fusion, and the characterization of reverse transcription/preintegration complexes formed in the infected cells, would provide further understanding in the contribution of the CA shell during HIV-1 post-entry steps. 2008 Retrovirology Discussion HIV S149A;S178A 25;15 30;20 RT;Capsid 117;257 138;259 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. This hypothesis was further confirmed using saturation assays of TRIM restriction factors performed in Cos7 monkey cells, as S149A viruses failed to release TRIM-mediated restriction observed in these cells. 2008 Retrovirology Discussion HIV S149A 125 130 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. This phenotype correlates with an early and total block in first-strand transfer DNA synthesis observed in cells infected with the S109A mutant. 2008 Retrovirology Discussion HIV S109A 131 136 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. This phenotype is very reminiscent of that reported by the Aiken laboratory for the Q63A/Q67A double mutant that displayed an unstable core structure and which was competent for RT. 2008 Retrovirology Discussion HIV Q63A;Q67A 84;89 88;93 RT 178 180 18605989 VSV-G pseudotyping rescues HIV-1 CA mutations that impair core assembly or stability. Unexpectedly, replication defects could be efficiently overcome by pseudotyping S149A and S178A viral particles with VSV-G, which was found to enhance late DNA synthesis and/or 2-LTR circle production. 2008 Retrovirology Discussion HIV S149A;S178A 80;90 85;95 LTR 179 182 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Although our analysis focused on the dynamics of the V38A mutation in the HR-1 domain of gp41, other mutations contributing to enfuvirtide resistance may have been present and could have contributed to overall viral fitness. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 53 57 gp41 89 93 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Consequently, the results presented here may not be representative of all patients with enfuvirtide failure associated with a V38A mutation. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 126 130 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Differences in the kinetics of the decay and re-emergence of V38A mutant virus reflect differences in the strength of the selection pressures applied in this study. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 61 65 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. For this reason, the presence or absence of V38A served only as a marker of viral turnover in response to enfuvirtide withdrawal or administration, and the fitness differences we observed cannot be ascribed solely to the presence of a valine or an alanine at amino acid 38. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 44 48 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. If replacement of the V38A mutants by wild-type virus with a higher replication capacity results in greater depletion of available target cells, it may be difficult to discern an impact of these mutations on viral load set-point. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 22 26 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. In addition, given the heterogeneity of HIV-1 env it is possible that the magnitude of the fitness differences we observed could vary depending on the specific envelope backbone in which the V38A mutation is found. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 191 195 Env;Env 160;46 168;49 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. In this study, use of an allele-specific PCR assay allowed us to track the decay of HIV-1 variants carrying the V38A mutation for enfuvirtide resistance in gp41. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 112 116 gp41 156 160 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Indirect evidence for this possibility is provided by the finding that in our study the level of V38A mutants detectable by allele-specific PCR never dropped below 1% of the population. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 97 101 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The more rapid turnover of the virus population during the enfuvirtide pulse suggests that enfuvirtide imposes stronger selective pressure on the virus population than does the partial treatment interruption, and that the advantage of the V38A mutant over wild-type in the presence of drug is greater than the disadvantage of the mutant compared to wild-type in the absence of drug. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 239 243 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The rapid re-emergence of the V38A mutant population could also be explained by a persistent reservoir of actively replicating mutant virus. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 30 34 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The V38A mutant population remained stable for 6 to 12 weeks in absence of enfuvirtide, and then decayed rapidly to less than 5% of the virus population over an additional 6 to 12 weeks. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 4 8 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. The V38A mutant re-emerged rapidly during the pulse intensification phase of this study and was accompanied by rapid rebound in plasma HIV-1 RNA levels. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 4 8 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. These results provide in vivo confirmation of earlier work from our group that demonstrated reduced fitness of the V38A mutant compared to wild-type virus in vitro. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 115 119 18645515 Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. Use of a growth corrected model for estimating fitness difference found that the V38A mutant viruses were 25% to 65% less fit than the wild-type in the absence of enfuvirtide. 2008 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V38A 81 85 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. In addition, several accessory INI-resistance mutations including V54I, L68V, L74M, T97A, V151I, G163R, I203M, and S230N also displayed levels of polymorphism ranging from 1% to 2%. 2008 Retrovirology Discussion HIV G163R;I203M;L68V;L74M;S230N;T97A;V151I;V54I 97;104;72;78;115;84;90;66 102;109;76;82;120;88;95;70 IN 31 34 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. In contrast, E157Q - which has been reported to be selected by raltegravir and to reduce elvitegravir susceptibility by about 3 to 6-fold - occurred in about 1% of untreated persons almost always in combination with the uncommon mutations K156N or K160Q. 2008 Retrovirology Discussion HIV E157Q;K156N;K160Q 13;239;248 18;244;253 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Most accessory INI-resistance mutations including L74R, Q95K, E138A/K, H183P, Y226C/D/F/H, S230R, and D232N were also nonpolymorphic. 2008 Retrovirology Discussion HIV D232N;E138A;E138K;H183P;L74R;Q95K;S230R;Y226C;Y226D;Y226F;Y226H 102;62;62;71;50;56;91;78;78;78;78 107;69;69;76;54;60;96;89;89;89;89 IN 15 18 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Mutations that have been selected in vitro or in vivo primarily by earlier INI compounds such as L-708,906, S-1360, and L-870,810 but which appear to be less essential for raltegravir or elvitegravir resistance include the highly polymorphic mutations V72I, V165I, and V201I; the minimally polymorphic mutation M154I; and the nonpolymorphic mutations T125K, A128T, and K160D. 2008 Retrovirology Discussion HIV A128T;K160D;M154I;T125K;V165I;V201I;V72I 358;369;311;351;258;269;252 363;374;316;356;263;274;256 IN 75 78 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Nearly all INI-resistance mutations known to directly reduce HIV-1 susceptibility were nonpolymorphic including H51Y, T66I, E92Q, F121Y, G140S, Y143C/H/R, Q146P, S147G, Q148H/R/K, S153Y, N155H/S, and R263K. 2008 Retrovirology Discussion HIV E92Q;F121Y;G140S;H51Y;N155H;N155S;Q146P;Q148H;Q148K;Q148R;R263K;S147G;S153Y;T66I;Y143C;Y143H;Y143R 124;130;137;112;187;187;155;169;169;169;200;162;180;118;144;144;144 128;135;142;116;194;194;160;178;178;178;205;167;185;122;153;153;153 IN 11 14 18687142 Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Recent independent surveys of isolates from smaller numbers of INI-naive individuals confirmed these results frequently finding E157Q as well as L74M, T97A, V151I, and I203M in small proportions of untreated persons. 2008 Retrovirology Discussion HIV E157Q;I203M;L74M;T97A;V151I 128;168;145;151;157 133;173;149;155;162 IN 63 66 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. 2.4-fold for the N155H mutant, respectively) might be due to differences in assay conditions and enzyme preparations. 2008 Biochemistry Discussion HIV N155H 17 22 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. And the third group comprises the S153Y mutation, which appears somewhat more selectively resistant to elvitegravir than raltegravir. 2008 Biochemistry Discussion HIV S153Y 34 39 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. IN S153Y and N155H are among the natural polymorphisms analyzed in the present study. 2008 Biochemistry Discussion HIV N155H;S153Y 13;3 18;8 IN 0 2 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Our data extend recent publications for raltegravir showing resistance for the E92Q and the N155H mutants. 2008 Biochemistry Discussion HIV E92Q;N155H 79;92 83;97 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The first includes mutations that confer no selectivity to either drug: L74M and E92Q. 2008 Biochemistry Discussion HIV E92Q;L74M 81;72 85;76 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The second group includes mutations that confer approximately 2-fold less resistance to raltegravir than elvitegravir (T66I, F121Y, Q148K and N155H). 2008 Biochemistry Discussion HIV F121Y;N155H;Q148K;T66I 125;142;132;119 130;147;137;123 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. The three most resistant enzymes (Q148K, T66I and S153Y) were also most defective in ST activity. 2008 Biochemistry Discussion HIV Q148K;S153Y;T66I 34;50;41 39;55;45 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Unexpectedly, we find that the S153Y IN mutant is markedly deficient in ST activity. 2008 Biochemistry Discussion HIV S153Y 31 36 IN 37 39 18702518 Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. who reported a 4.3-fold resistance level for the E92Q mutant (we found 3.5-fold; see Figure 6E). 2008 Biochemistry Discussion HIV E92Q 49 53 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. An N197D mutation in Env improved CXCR4 utilisation by HIV ADA-1 following co-receptor switching from CCR5 to CXCR4. 2008 Retrovirology Discussion HIV N197D 3 8 Env 21 24 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. However as the Fel-O-Vax FIV vaccine is derived from FL4 virus bearing the T271I and N342Y mutations, it is possible that deglycosylation of this region in the vaccine strain may render the region immunogenic for vaccinates and contribute to protection from challenge. 2008 Retrovirology Discussion HIV N342Y;T271I 85;75 90;80 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. If N-linked glycosylation at N-269 contributes to the complexity of the Env-CD134 interaction in vivo, we would predict that late isolates of FIV would be more likely to harbour viral variants bearing mutations such as the T271I observed in FL4. 2008 Retrovirology Discussion HIV T271I 223 228 Env 72 75 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. In this study, we found that the T271I mutation did not confer CD134-independent infection, rather it modulated usage of CD134 by the primary FIV Envs, reducing the requirement for residues in CRD2 of CD134 for viral entry and syncytium formation. 2008 Retrovirology Discussion HIV T271I 33 38 Env 146 150 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Neither the T271 nor the N342Y mutations affected the sensitivity of GL8 to neutralisation by sera from cats infected with the biological isolate of GL8, suggesting that this region may not be a primary target for neutralising antibodies in vivo. 2008 Retrovirology Discussion HIV N342Y 25 30 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Sequence analysis revealed an I271T reversion in 2 out of 3 cats and Y342N mutation in 3 of 3 cats, suggesting a strong selective pressure in favour of either reinstating the N-linked glycosylation sites following infection or suppressing the replication of T271I and Y342N bearing variants in vivo. 2008 Retrovirology Discussion HIV I271T;T271I;Y342N;Y342N 30;258;69;268 35;263;74;273 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. That the removal of a single site for N-linked glycosylation (T271I) is sufficient to switch both GL8 and CPG41 from a complex to a minimal interaction would suggest that the N-linked glycosylation site ablated by the T271I mutation either forms a component of the receptor binding face of FIV Env, or contributes to the tertiary/quaternary structure of the Env trimer such that the receptor binding face of Env is presented to the viral receptor in the correct configuration. 2008 Retrovirology Discussion HIV T271I;T271I 62;218 67;223 Env;Env;Env 294;358;408 297;361;411 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The location of these mutations, T271I and N342Y, is strikingly similar to previously described N-linked glycosylation sites in the Env of SIV and HIV that may contribute to enhanced immunogenicity of Env-based immunogens and an altered receptor usage in vitro . 2008 Retrovirology Discussion HIV N342Y;T271I 43;33 48;38 Env;Env 132;201 135;204 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The mutations in V3 that conferred CXCR4 usage upon the virus were in themselves deleterious; it has been suggested that by altering the flexibility of the V1V2 loop, the N197D mutation compensated for the mutations in V3 that facilitated switching from CCR5 to CXCR4 usage. 2008 Retrovirology Discussion HIV N197D 171 176 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The N-linked glycosylation sites affected by the T271I and N342Y mutations in FIV lie in a predicted loop domain of FIV Env that is analogous to the V1/V2 loop of HIV in schematic structural models. 2008 Retrovirology Discussion HIV N342Y;T271I 59;49 64;54 Env 120 123 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. The T271I mutation in FIV Env may have a similar function; either by altering directly a contact point with CD134 or by facilitating CD134-independent infection. 2008 Retrovirology Discussion HIV T271I 4 9 Env 26 29 18721458 A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. When the T271I and N342Y mutations were introduced into two primary field strains of FIV (GL8 and CPG41), the T271I mutation was shown to have a significant modulatory effect on the way the virus interacts with CD134. 2008 Retrovirology Discussion HIV N342Y;T271I;T271I 19;9;110 24;14;115 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. A similar intracellular distribution of non-fluorescently labelled L23F-Vpr has been previously found by immunofluorescence, indicating that eGFP did not interfere with the cellular distribution of such Vpr mutants. 2008 Retrovirology Discussion HIV L23F 67 71 Vpr;Vpr 72;203 75;206 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. For instance, the L23F mutation that alters the Vpr-hCG1 complex was recently shown to cause a lack of Vpr accumulation at the nuclear rim. 2008 Retrovirology Discussion HIV L23F 18 22 Vpr;Vpr 48;103 51;106 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. In a first step, we characterized the L23F, I60A and L67A mutations of the hydrophobic central core. 2008 Retrovirology Discussion HIV I60A;L23F;L67A 44;38;53 48;42;57 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. In contrast to the aforementioned mutants, a wild type Vpr docking at the nuclear rim was observed for mutations in the loops (W54G, R77Q) and the flexible N- and C- terminal regions (Q3R, R90K), indicating that these residues are dispensable for Vpr cellular localization. 2008 Retrovirology Discussion HIV Q3R;R77Q;R90K;W54G 184;133;189;127 187;137;193;131 Vpr;Vpr 55;247 58;250 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Moreover, the peri-nuclear localization of the I60A-Vpr mutant was recovered upon co-expression with Vpr-mCherry (data not shown). 2008 Retrovirology Discussion HIV I60A 47 51 Vpr;Vpr 52;101 55;104 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. The apoptotic activity of the Q3R and R77Q Vpr mutants are in variance with published reports but could be explained by a possible eGFP-mediated gain of function. 2008 Retrovirology Discussion HIV Q3R;R77Q 30;38 33;42 Vpr 43 46 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. The DeltaQ44 mutation drastically impaired the oligomerization and localization of Vpr at the nuclear envelope, further suggesting a direct correlation between these two phenomena. 2008 Retrovirology Discussion HIV DeltaQ44 4 12 Env;Vpr 102;83 110;86 18808682 Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. The L23F and L67A Vpr mutants were distributed throughout the cell, indicating that these residues are critical for addressing Vpr at the nuclear envelope. 2008 Retrovirology Discussion HIV L23F;L67A 4;13 8;17 Env;Vpr;Vpr 146;18;127 154;21;130 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. A major difference between the effects of these latter two inhibitors is the effect of the D25N mutation, such that the binding of Ac-PEP to PRD25N (DeltaTm < 1 C) was virtually nil, whereas the binding of RPB increased its Tm by ~6 C. 2009 Proteins Discussion HIV D25N 91 95 PR 141 143 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. Binding of the extended, substrate-like molecules RPB and Ac-PEP was almost completely abolished by the D29N mutation, such that these inhibitors, which increase the Tm of PR by ~9 and 6.5 C, respectively, had virtually no effect on the Tm of PRD29N. 2009 Proteins Discussion HIV D29N 104 108 PR;PR 172;244 174;246 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. Both are highly sensitive to the D29N substitution. 2009 Proteins Discussion HIV D29N 33 37 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. In contrast, binding of the cyclic, symmetrical inhibitor DMP323 was less affected by the D25N mutation. 2009 Proteins Discussion HIV D25N 90 94 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. RPB binding is much less affected by the D25N mutation (DeltaTm ratio 1.4) than Ac-PEP (DeltaTm ratio 16.2) because RPB lacks the hydroxyl (shown in red for all the other inhibitors in. 2009 Proteins Discussion HIV D25N 41 45 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. The D29N substitution has smaller but significant effects on DeltaTm for these inhibitors. 2009 Proteins Discussion HIV D29N 4 8 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. This relative lack of sensitivity to the D25N mutation is quite surprising, but may result from differences between the geometry of the symmetrical pair of hydroxyl groups in DMP323 compared to the single hydroxyl that is present in the other inhibitors. 2009 Proteins Discussion HIV D25N 41 45 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. Thus all the drugs, with the notable exception of APV, exhibit similar sensitivities to the D25N mutation (DeltaTm ratios in the range of 5-7). 2009 Proteins Discussion HIV D25N 92 96 18951411 Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin. We speculate that these enhanced interactions with DRV may help to compensate for the substitution of Asp25 in the D25N mutant, whereas the binding of APV depends much more heavily on interactions mediated by the catalytic Asp25 residues. 2009 Proteins Discussion HIV D25N 115 119 Asp;Asp 102;223 105;226 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Although the PR mutations D30N and L90M both develop in non-B viruses during NFV therapy, they occur more commonly in subtype B, what was confirmed in our comparison with subtype F1. 2009 Infection, genetics and evolution Discussion HIV D30N;L90M 26;35 30;39 PR 13 15 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Conversely, K20T and N88S were specifically selected in subtype F1 as a consequence of PI treatment. 2009 Infection, genetics and evolution Discussion HIV K20T;N88S 12;21 16;25 PI 87 89 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Finally, the comparison of both subtype groups matched for treatment time exposure to the PI class or, when appropriated, to specific PI showed that mutations K20M, D30N (under NFV-containing regimens or under NFV as the unique PI), G73S, I84V, and L90M (under NFV as the unique PI) were more prevalent in subtype B. 2009 Infection, genetics and evolution Discussion HIV D30N;G73S;I84V;K20M;L90M 165;233;239;159;249 169;237;243;163;253 PI;PI;PI;PI 90;134;228;279 92;136;230;281 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. However, in agreement with our results, recent data identified selection of N88S and K20T by NFV treatment, which suggests that N88S might be more important than D30N and L90M in subtypes A1 and F1 and should be considered a major mutation, pointing out different roles for N88D and N88S in NFV resistance. 2009 Infection, genetics and evolution Discussion HIV D30N;K20T;L90M;N88D;N88S;N88S;N88S 162;85;171;274;76;128;283 166;89;175;278;80;132;287 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In the case of L63P, we failed to detect differences between naive and treated subtype B sequences because this polymorphism is high in Brazilian viruses of this subtype. 2009 Infection, genetics and evolution Discussion HIV L63P 15 19 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. In untreated patients, mutations L63P, A71T, and V77I were more prevalent in isolates of subtype B, while L10V, K20R, and M36I were significantly more frequent in subtype F1 isolates. 2009 Infection, genetics and evolution Discussion HIV A71T;K20R;L10V;L63P;M36I;V77I 39;112;106;33;122;49 43;116;110;37;126;53 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Indeed, we observed a higher prevalence of I84V in B versus F1 viruses also in a subset of isolates from patients matched for the same treatment time with IDV and/or RTV (_APV). 2009 Infection, genetics and evolution Discussion HIV I84V 43 47 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Interestingly, did not observe a higher prevalence of D30N, but rather a higher prevalence of A71V and V77I in subtype B compared with subtype F viruses isolated from treated patients. 2009 Infection, genetics and evolution Discussion HIV A71V;D30N;V77I 94;54;103 98;58;107 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Interestingly, V82L reported by IAS consensus as a major mutation specifically associated with resistance to tipranavir, not used by our cohort, was observed in subtypes B and F1 isolated from treated children but not in adults. 2009 Infection, genetics and evolution Discussion HIV V82L 15 19 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Moreover, despite the treatment history of B- and F1-infected adult patients was comparable, we could find subtype F1-specific treatment-related mutations, as K20T, L63P and N88S were more frequent only in treated than in untreated people infected with subtype F1, while L10V, K20M, D30N, L33F, M36I, M46I, G73S, N88D and I84V were more prevalent in treated than in untreated patients infected only with subtype B. 2009 Infection, genetics and evolution Discussion HIV D30N;G73S;I84V;K20M;K20T;L10V;L33F;L63P;M36I;M46I;N88D;N88S 283;307;322;277;159;271;289;165;295;301;313;174 287;311;326;281;163;275;293;169;299;305;317;178 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Moreover, the proportion of L10I to L10V is inverted when comparing both groups of untreated patients. 2009 Infection, genetics and evolution Discussion HIV L10I;L10V 28;36 32;40 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. Mutations N88S and K20T are respectively reported by IAS consensus as major and minor mutations specifically associated with resistance to atazanavir, not used by our cohort, while N88D/S are considered minor mutations associated with resistance to NFV. 2009 Infection, genetics and evolution Discussion HIV K20T;N88D;N88S;N88S 19;181;181;10 23;187;187;14 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. suggested that M46I and M46L lie along divergent evolutionary pathways, what has been supported by others. 2009 Infection, genetics and evolution Discussion HIV M46I;M46L 15;24 19;28 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. The higher prevalence of I84V in subtype B has been reported. 2009 Infection, genetics and evolution Discussion HIV I84V 25 29 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. The mutations L10F/R, K20I, V32I, I47V/A, I50L/V, I54L/A/M/T/S, A71T, G73C/T/A, V77I, and V82F/T/S, either absent or observed in our subtype B and F1 viruses, were not statistically different in viruses isolated from treated or untreated patients. 2009 Infection, genetics and evolution Discussion HIV A71T;G73A;G73C;G73T;I47A;I47V;I50L;I50V;I54A;I54L;I54M;I54S;I54T;K20I;L10F;L10R;V32I;V77I;V82F;V82S;V82T 64;70;70;70;34;34;42;42;50;50;50;50;50;22;14;14;28;80;90;90;90 68;78;78;78;40;40;48;48;62;62;62;62;62;26;20;20;32;84;98;98;98 18992847 Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure. We observed different proportions of M46I to M46L mutations between treated subtype groups (B and F1), and M46I behaved as a treatment-related mutation only for subtype B in our cohort. 2009 Infection, genetics and evolution Discussion HIV M46I;M46I;M46L 37;107;45 41;111;49 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. Another unique feature of subtype C virus is that the K65R mutation which develops in subtype C is AGG, whereas in subtype B it is almost exclusively AGA (data not shown). 2008 AIDS (London, England) Discussion HIV K65R 54 58 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. described a G48G silent mutation within the protease region of subtype C subtypes, as well as a T215T silent mutation present in subtype A and A/E subtypes. 2008 AIDS (London, England) Discussion HIV G48G;T215T 12;96 16;101 PR 44 52 19005273 Silent mutations are selected in HIV-1 reverse transcriptase and affect enzymatic efficiency. There have been recent suggestions that silent mutations in the subtype C RT gene were responsible for the rapid selection of the K65R mutation. 2008 AIDS (London, England) Discussion HIV K65R 130 134 RT 74 76 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. However, their study also indicated that the K186Q mutant interacted with LEDGF/p75 as efficiently as the wild type IN in a two-hybrid assay. 2008 Retrovirology Discussion HIV K186Q 45 50 IN 116 118 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. In contrast to a previous study, our experiments revealed that this IN-induced lethality was independent of the catalytic activity of IN, since two catalytically inactive IN mutants (D64E and D116A) were still able to induce the lethal phenotype in our experimental system. 2008 Retrovirology Discussion HIV D116A;D64E 192;183 197;188 IN;IN;IN 68;134;171 70;136;173 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. In this study, we confirmed that the V165A mutant was indeed unable to interact with LEDGF/p75. 2008 Retrovirology Discussion HIV V165A 37 42 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. It has also been shown that the V165A and L172A/K173A mutants were unable to bind LEDGF/p75 in vitro . 2008 Retrovirology Discussion HIV K173A;L172A;V165A 48;42;32 53;47;37 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. It should be noticed that D64E was less efficient in complementing the A179P and KR186,7AA mutants than the V165A mutant. 2008 Retrovirology Discussion HIV A179P;D64E;V165A 71;26;108 76;30;113 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Moreover, two other IN mutants (A179P and KR186,7AA) were identified in this study that were incapable of binding to both LEDGF/p75 and to chromatin. 2008 Retrovirology Discussion HIV A179P 32 37 IN 20 22 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Several studies have suggested that the IN-induced lethal phenotype may be related to the catalytic activity of IN, as an IN catalytic mutant (D116A) was unable to induce lethality in yeast. 2008 Retrovirology Discussion HIV D116A 143 148 IN;IN;IN 40;112;122 42;114;124 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Similar to the IN class I mutant D64E, all yeast lethal phenotype-defective IN mutant viruses were replication deficient. 2008 Retrovirology Discussion HIV D64E 33 37 IN;IN 15;76 17;78 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. These results are consistent with a previous report by Lu et al that showed that the catalytically active IN mutants V165A and K186Q were able to complement the D64N/D116N mutant virus. 2008 Retrovirology Discussion HIV D116N;D64N;K186Q;V165A 166;161;127;117 171;165;132;122 IN 106 108 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Three IN mutants (V165A, A179P and KR186,7AA) were identified as lethal phenotype-defective mutants in HP16 cells. 2008 Retrovirology Discussion HIV A179P;V165A 25;18 30;23 IN 6 8 19014595 Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication. Using semi-quantitative PCR, we showed that all three yeast lethal-defective IN mutants did not affect reverse transcription and these IN mutant viruses could be complemented by the D64E mutant. 2008 Retrovirology Discussion HIV D64E 182 186 RT;IN;IN 103;77;135 124;79;137 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. A C130S substitution in combination with three other mutations shows loss in strand transfer but with some decrease in 3' processing. 2009 Journal of molecular biology Discussion HIV C130S 2 7 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. A K219A mutation has been analyzed for its effect on HIV-1 replication and was reported to have a limited affect. 2009 Journal of molecular biology Discussion HIV K219A 0 7 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. A N120S mutant is reported to increase 3' processing and strand transfer activities while N120Q and N120K mutants show little effect on processing but some decrease in strand transfer. 2009 Journal of molecular biology Discussion HIV N120K;N120Q;N120S 100;90;2 105;95;7 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. A T125S substitution increases the 3' processing of U5 HIV-1 duplex as well as joining of a HIV-1 preprocessed substrate. 2009 Journal of molecular biology Discussion HIV T125S 2 7 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. As reported here, the K219S mutation also loses strand transfer but maintains 3' processing activity. 2009 Journal of molecular biology Discussion HIV K219S 22 27 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. Changes at position 230 are reported to appear in conjunction with T66I and M74L substitutions in cells. 2009 Journal of molecular biology Discussion HIV M74L;T66I 76;67 80;71 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. Finally, HIV-1 IN substitutions of I141K, I203P or I203K (Corinne Ronfort, Universite de Lyon, personal communication) also show a loss in strand transfer with little affect on 3' processing. 2009 Journal of molecular biology Discussion HIV I141K;I203K;I203P 35;51;42 40;56;47 IN 15 17 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. In contrast, the substitution at position 72 (V72W) caused a larger decrease in the ability to process the HIV-1 U5 duplex substrate. 2009 Journal of molecular biology Discussion HIV V72W 46 50 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. More recently, four HIV-1 IN mutants with W132Y, M178C, F181G, and F185G substitutions, respectively, were constructed. 2009 Journal of molecular biology Discussion HIV F181G;F185G;M178C;W132Y 56;67;49;42 61;72;54;47 IN 26 28 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. On this basis, we would predict that the V72I drug resistant mutation would appear in the presence of other substitutions that compensate for the loss in its 3' processing towards HIV-1 substrates. 2009 Journal of molecular biology Discussion HIV V72I 41 45 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. Second site mutations of F121Y and T125K subsequently appear in HIV-1 IN containing the V72I mutation. 2009 Journal of molecular biology Discussion HIV F121Y;T125K;V72I 25;35;88 30;40;92 IN 70 72 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. The C130S and W132A/G/R substitutions are reported to have normal 3' processing but little or no joining activity. 2009 Journal of molecular biology Discussion HIV C130S;W132A;W132G;W132R 4;14;14;14 9;23;23;23 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. The K211S mutation has no affect on activity of IN in vitro. 2009 Journal of molecular biology Discussion HIV K211S 4 9 IN 48 50 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. We have not analyzed substitutions at position 66 in vitro, but Lee and Robinson reported that the T66I substitution caused a small decrease in 3' processing. 2009 Journal of molecular biology Discussion HIV T66I 99 103 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. We tested a M74A substitution that resulted in a significant loss of 3' processing of HIV-1 substrates. 2009 Journal of molecular biology Discussion HIV M74A 12 16 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. When combined with the V72W mutation, this produces an enzyme with near wild type levels of 3' processing, suggesting that a second site mutation compensates for the decrease in 3' processing caused by the initial drug resistant mutation. 2009 Journal of molecular biology Discussion HIV V72W 23 27 19014951 Defining the DNA substrate binding sites on HIV-1 integrase. With the caveat that the exchange of S230E was analyzed as a double mutant in combination with D229I, it gained the ability to cleave the ASV substrate, but in contrast to chimeras with changes at positions 72 or 153, it displayed an increase in activity towards HIV-1 substrates. 2009 Journal of molecular biology Discussion HIV D229I;S230E 95;37 100;42 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. It should be noted that virus with the A147T substitution could not be isolated from the two macaques in which it was observed. 2009 Virology Discussion HIV A147T 39 44 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. Perhaps the A147T substitution permitted more replication in macaques RAK10 and RPL10 resulting in a better antigenic stimulus. 2009 Virology Discussion HIV A147T 12 17 19027134 Mutations in the highly conserved SLQYLA motif of Vif in a simian-human immunodeficiency virus result in a less pathogenic virus and are associated with G-to-A mutations in the viral genome. Whether this relates to the inability to select for the A147T amino acid substitution is currently unknown. 2009 Virology Discussion HIV A147T 56 61 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Abbreviations: RT, reverse transcriptase; RNase H, ribonuclease H; RTI, RT inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; AZT, zidovudine or 3'-azido-3'-dideoxythymidine; TP, triphosphate; TAMs, thymidine analogue mutations; WT, wild type; MP, monophosphate; T/P, template/primer; AZTR, D67N/K70R/T215F; nt, nucleotide. 2008 Biochemistry Discussion HIV D67N;K70R;T215F 355;360;365 359;364;370 NNRTI;NRTI;RT;NNRTI;NRTI;RT;RT;RT 143;92;19;136;86;67;15;72 178;124;40;141;90;70;17;74 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Because the Q509L mutation decreases the rate of TRNA10/PAZT product formation (to 0.01 min-1), it favors AZT-MP excision at 0.3 mM ATP. 2008 Biochemistry Discussion HIV Q509L 12 17 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. By using a well-defined RNA/DNA T/P, we show that AZTR/Q509L increases the efficiency of AZT-MP excision by decreasing the frequency of a secondary RNase H cleavage event that reduces the RNA/DNA duplex to 10 nts. 2008 Biochemistry Discussion HIV Q509L 55 60 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. For example, G333D in HIV-1 RT allows the enzyme to effectively discriminate between the normal substrate dCTP and lamivudine-triphosphate. 2008 Biochemistry Discussion HIV G333D 13 18 RT 28 30 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. have proposed a similar model for the N348I and A360V connection domain mutations. 2008 Biochemistry Discussion HIV A360V;N348I 48;38 53;43 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. However, even on this T/P, the AZTR/Q509L enzyme has a significantly better ability to unblock the chain-terminated primer than WT or AZTR. 2008 Biochemistry Discussion HIV Q509L 36 41 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In conclusion, our data provide evidence that Q509L in HIV-1 RT confers AZT resistance by affecting the balance between AZT-MP excision and RNase H activities of RT on RNA/DNA T/P. 2008 Biochemistry Discussion HIV Q509L 46 51 RT;RT 61;162 63;164 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In Figure 6, we propose a model, based on our findings, to explain how Q509L decreases the RNase H activity of RT. 2008 Biochemistry Discussion HIV Q509L 71 76 RT 111 113 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. In our study, we show by transient kinetic analyses that Q509L does not impact the rates of the initial polymerase-directed RNase H cleavage, but only polymerase-independent cleavages that occur after a T/P dissociation event (Figure 4). 2008 Biochemistry Discussion HIV Q509L 57 62 Pol;Pol 104;151 114;161 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. It also enhances the ability of RT containing TAMs and M184V to bind AZT-MP terminated T/P, thereby restoring ATP-mediated excision of AZT-MP. 2008 Biochemistry Discussion HIV M184V 55 60 RT 32 34 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. It is also important to understand that the kinetics of AZT-MP excision are dependent on nucleic acid sequence and structure, and therefore, Q509L will likely show a greater effect at positions where AZT-MP excision is slow. 2008 Biochemistry Discussion HIV Q509L 141 146 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Our data show that Q509L selectively decreases the affinity of RT binding to TRNA16/PAZT in an RNase H competent mode but not in an excision competent mode. 2008 Biochemistry Discussion HIV Q509L 19 24 RT 63 65 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Our studies demonstrate that the Q509L mutation confers AZT resistance by increasing the AZT-MP excision activity of the enzyme via an RNase H-dependent mechanism. 2008 Biochemistry Discussion HIV Q509L 33 38 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Q509L does not appear to directly decrease the RNase H activity of RT, rather it affects the enzyme's ability to bind T/P with short RNA/DNA duplexes in a polymerase-independent RNase H cleavage mode. 2008 Biochemistry Discussion HIV Q509L 0 5 Pol;RT 155;67 165;69 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Recently, however, we carried out in Vitro selections of HIV-1 with AZT and identified the Q509L mutation in the RNase H domain of RT that was selected in combination with D67N, K70R, and T215F. 2008 Biochemistry Discussion HIV D67N;K70R;Q509L;T215F 172;178;91;188 176;182;96;193 RT 131 133 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. The fact that the increase in excision efficiency for the AZTR/Q509L RT, observed in Figure 1B, is driven by an increase in burst concentration and not rate is entirely consistent with a model of competition between RNA template degradation and AZT-MP excision. 2008 Biochemistry Discussion HIV Q509L 63 68 RT 69 71 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. This hypothesis is supported by the results showing that AZTR/Q509L RT exhibits a significant advantage over the AZTR enzyme at 3 mM ATP in assays that evaluate multiple AZT-TP and AZT-MP excision events (Figure 3). 2008 Biochemistry Discussion HIV Q509L 62 67 RT 68 70 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. We also addressed the mechanism by which Q509L decreases the RNase H activity of RT. 2008 Biochemistry Discussion HIV Q509L 41 46 RT 81 83 19067547 Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. We and others have also demonstrated that mutations, such as N348I, may increase AZT resistance by decreasing RNA template degradation. 2008 Biochemistry Discussion HIV N348I 61 66 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. In addition, native TK2 TGs exhibited neither CM nor changes in mtDNA at 3 weeks compared to Y955C TGs. 2009 Laboratory investigation; a journal of technical methods and pathology Discussion HIV Y955C 93 98 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Mutant TGs (Y955C, H121N, and I212N) had greater impact on changes in mtDNA abundance and cardiac dysfunction than native TK2. 2009 Laboratory investigation; a journal of technical methods and pathology Discussion HIV H121N;I212N;Y955C 19;30;12 24;35;17 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Of the TGs examined here, Y955C caused the worst defects in cardiac mtDNA replication both in amplitude and rapidity of onset. 2009 Laboratory investigation; a journal of technical methods and pathology Discussion HIV Y955C 26 31 19079325 Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation. Y955C disrupted mtDNA replication early. 2009 Laboratory investigation; a journal of technical methods and pathology Discussion HIV Y955C 0 5 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. The predominant transmitted variants, here, were Y188C/H and K103N, reflective of the most common mutations found in women following SD-NVP exposure. 2009 PloS one Discussion HIV K103N;Y188C;Y188H 61;49;49 66;56;56 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. The types of NVP-resistance mutations were similar between the two intervention groups but differed by timing of infection, where the Y181C variant was predominant in infections occurring in the first six weeks of life compared to the Y188C/H variant associated with late breast-milk infections. 2009 PloS one Discussion HIV Y181C;Y188C;Y188H 134;235;235 139;242;242 19119321 Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. The Y181C variant remained dominant as observed in studies of NVP-R following single-dose exposure in infants and in earlier studies of daily NVP monotherapy for treatment of infected individuals. 2009 PloS one Discussion HIV Y181C 4 9 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. In order to reduce this effect, we had designed an analog of the alpha4 peptide that had its secondary structure stabilized by helicogenic mutations (Gly149Ala, Ile161Leu, Ile162Leu and Gly163Ala). 2009 PloS one Discussion HIV G149A;G163A;I161L;I162L 150;186;161;172 159;195;170;181 19119323 An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF. Resembling the IN CC, the peptide HTHi binds wt IBD, but not its Asp366Asn variant. 2009 PloS one Discussion HIV D366N 65 74 Asp;IN 65;15 68;17 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. and our study show that the G140S mutation rescues the ability of the Q148H/K/R mutants to replicate in cells while mutation of the Q148 residue is responsible for the resistance to the drug. 2009 Nucleic acids research Discussion HIV G140S;Q148H;Q148K;Q148R 28;70;70;70 33;79;79;79 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Consistently, all mutants are weakly impaired in the synthesis of viral DNA as well as in their propensity to integrate their genome and consequently to produce viral particles with the notable exception of the Q148H mutant. 2009 Nucleic acids research Discussion HIV Q148H 211 216 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. have shown that the G140S mutation rescues the fitness of the Q148K/R mutant. 2009 Nucleic acids research Discussion HIV G140S;Q148K;Q148R 20;62;62 25;69;69 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. However, 8-10 weeks later, the G140S mutation is also detected in patients. 2009 Nucleic acids research Discussion HIV G140S 31 36 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. However, continued drug development is required as the ability of HIV to replicate under therapeutic pressure will undoubtedly lead to the emergence of IN drug-resistant viral strains characterized by comparable fitness to WT such as the double mutant G140S/Q148H. 2009 Nucleic acids research Discussion HIV G140S;Q148H 252;258 257;263 IN 152 154 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. However, we found that the integration efficiency of the G140S was similar to those found for the WT and G140S/Q148H double mutant. 2009 Nucleic acids research Discussion HIV G140S;G140S;Q148H 57;105;111 62;110;116 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Importantly, the G140S displays weak resistance (IC50 = 30 nM) while the Q148H is strongly resistant to RAL (IC50 > 700 nM). 2009 Nucleic acids research Discussion HIV G140S;Q148H 17;73 22;78 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In addition, our data demonstrate that the Q148H mutant is more resistant to RAL in comparison to the N155H mutant. 2009 Nucleic acids research Discussion HIV N155H;Q148H 102;43 107;48 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In the case of the G140S mutant, the viral fitness is only delayed in Jurkat cells. 2009 Nucleic acids research Discussion HIV G140S 19 24 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. In the viral context, all mutants, including G140S, displayed replication kinetics similar to those to the WT virus, with the exception of the Q148H mutant which is characterized by a slower kinetic. 2009 Nucleic acids research Discussion HIV G140S;Q148H 45;143 50;148 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. It is important to note that beta-Gal assays using the HeLa-P4 cells suggests that the G140S mutant was impaired in the viral integration process, in accordance with results of Nakahara et al. 2009 Nucleic acids research Discussion HIV G140S 87 92 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. It is important to note that the Q148H/R single mutation may occur 8 weeks after starting RAL treatment. 2009 Nucleic acids research Discussion HIV Q148H;Q148R 33;33 40;40 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Mutants Q148K/R displayed reduced viral fitness whatever the cell line studied (PBMC or Jurkat cells). 2009 Nucleic acids research Discussion HIV Q148K;Q148R 8;8 15;15 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Nevertheless, the slower kinetic of either G140S or G140S/Q148H, as seen in vitro, had no effect on the replication cycle of corresponding viruses. 2009 Nucleic acids research Discussion HIV G140S;G140S;Q148H 43;52;58 48;57;63 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Our data of the compensation of the Q148H replication efficiency by the G140S explain why very rapidly after the administration of RAL, the G140S/Q148H mutant is detected. 2009 Nucleic acids research Discussion HIV G140S;G140S;Q148H;Q148H 72;140;36;146 77;145;41;151 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Such a differential response of the G140S mutation depending on the cellular context could account for the lack of correlation between beta-Gal assays (Figure 1) and integration quantification (Figure 3). 2009 Nucleic acids research Discussion HIV G140S 36 41 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Taken together, these data suggest that resistance results principally from the Q148H mutation. 2009 Nucleic acids research Discussion HIV Q148H 80 85 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Taken together, we hypothesized that the Q148H mutation primarily confers resistance to RAL. 2009 Nucleic acids research Discussion HIV Q148H 41 46 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The authors have studied the Q148K/R and G140S mutations as well as the G140S/Q148R and G140S/Q148K double mutants. 2009 Nucleic acids research Discussion HIV G140S;G140S;G140S;Q148K;Q148K;Q148R;Q148R 41;72;88;94;29;29;78 46;77;93;99;36;36;83 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The G140S mutation counteracted this detrimental effect for the virus and increased viral fitness. 2009 Nucleic acids research Discussion HIV G140S 4 9 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The G140S/Q148H double mutation confers strong resistance to the drug and viral replication levels similar to those of the WT virus. 2009 Nucleic acids research Discussion HIV G140S;Q148H 4;10 9;15 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. The Q148H IN was much more severely impaired and cannot reach the WT level of activity (thermodynamic mutant). 2009 Nucleic acids research Discussion HIV Q148H 4 9 IN 10 12 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. These data clearly account for the high frequency of the G140S/Q148H mutant in clinical trials. 2009 Nucleic acids research Discussion HIV G140S;Q148H 57;63 62;68 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. These data demonstrate that, in the case of the G140S/Q148H double mutant, the resistance to RAL is due to the Q148H and that the G140S mutation rescues the integration deficiency and thus the kinetic of replication. 2009 Nucleic acids research Discussion HIV G140S;G140S;Q148H;Q148H 48;130;54;111 53;135;59;116 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. These mutations are E92Q, N155H and the G140S/Q148H double mutation, which seems to appear preferentially. 2009 Nucleic acids research Discussion HIV E92Q;G140S;N155H;Q148H 20;40;26;46 24;45;31;51 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. To date, the reason of such discrepancy is not clear but the type of cells used for integration quantification could be crucial in modulating the mutation impact, especially in the case of the G140S mutation. 2009 Nucleic acids research Discussion HIV G140S 193 198 19129221 The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. We observed that G140S/Q148H IN, although kinetically affected as compared to the WT IN, displayed WT levels of activity if the incubation time was increased (kinetic mutant). 2009 Nucleic acids research Discussion HIV G140S;Q148H 17;23 22;28 IN;IN 29;85 31;87 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. A smaller proportion of women (3%) had K103N mutations detected in viral DNA, possibly because we extracted total DNA from buffy coats. 2009 Clinical infectious diseases Discussion HIV K103N 39 44 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. All K103N genotype-positive samples yielded highly positive results by AS-PCR. 2009 Clinical infectious diseases Discussion HIV K103N 4 9 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Approximately 10% of sdNVP-exposed women had K103N mutations before treatment that we detected in viral RNA using AS-PCR, a method capable of detecting this point mutation if it is present at levels less than the threshold of population sequencing. 2009 Clinical infectious diseases Discussion HIV K103N 45 50 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. However, this suppression was often not sustained among those whose K103N mutations were detected before the commencement of treatment. 2009 Clinical infectious diseases Discussion HIV K103N 68 73 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. One case involving a high concentration of K103N mutations noted by AS-PCR but a genotype negative for K103N may have resulted from polymorphisms in the primer-binding regions. 2009 Clinical infectious diseases Discussion HIV K103N;K103N 43;103 48;108 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Ours is not the first study to observe K103N mutations among apparently unexposed women. 2009 Clinical infectious diseases Discussion HIV K103N 39 44 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. The association between K103N mutations and viral response was not absolute: ~40% of women with K103N mutations still had durable responses, and one-third of women with inadequate viral responses experienced resuppression of the viral load without a change in regimen, after adherence support was intensified. 2009 Clinical infectious diseases Discussion HIV K103N;K103N 24;96 29;101 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. We demonstrate that K103N mutations detectable by AS-PCR were strongly associated with inadequate virologic responses to NNRTI-based therapy. 2009 Clinical infectious diseases Discussion HIV K103N 20 25 NNRTI 121 126 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. We noted that K103R mutations interfered with detection of K103N mutations. 2009 Clinical infectious diseases Discussion HIV K103N;K103R 59;14 64;19 19133804 Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. We tested for the K103N mutation with the AS-PCR assay, because this is the mutation most frequently selected by sdNVP exposure. 2009 Clinical infectious diseases Discussion HIV K103N 18 23 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. A recent report suggested that K65R may be associated with abacavir resistance in HIV-2, but the patients in that report with virus with the K65R mutation also received AZT and 3TC. 2009 Clinical infectious diseases Discussion HIV K65R;K65R 31;141 35;145 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. However, the authors did find high treatment failure rates, RT mutations M184V/I and Q151M, and the PR mutation L90M in the virus strains from 7 patients who received NRTI- and nelfinavir-based regimens. 2009 Clinical infectious diseases Discussion HIV L90M;M184I;M184V;Q151M 112;73;73;85 116;80;80;90 NRTI;PR;RT 167;100;60 171;102;62 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. However, the RT Q151M mutation, which confers multinucleoside resistance in HIV-2, occurred relatively frequently (in 17% of patients infected with ARV- resistant virus), an observation that has been noted in other cohorts. 2009 Clinical infectious diseases Discussion HIV Q151M 16 21 RT 13 15 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. In contrast to what has been reported for HIV-1 infection treated with regimens containing AZT, thymidine analog mutations were rare in HIV-2, with 1 patient infected with a strain harboring the K70R mutation (a mutation of unknown significance in HIV-2). 2009 Clinical infectious diseases Discussion HIV K70R 195 199 HIV infections 42 57 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. No data on K7R or L99F phenotypic resistance are available for HIV-2 group B strains. 2009 Clinical infectious diseases Discussion HIV K7R;L99F 11;18 14;22 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. One patient (patient H2A17) in our study was infected with a group B HIV-2 strain; the majority of HIV-2 group B sequences (in ARV therapy- naive patients) have K7R and L99F mutations present naturally, although at least 1 report describes 2 ARV therapy-naive patients with HIV-2 group B strains with the 99 L "mutation." Colson et al. 2009 Clinical infectious diseases Discussion HIV K7R;L99F 161;169 164;173 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Phenotypic resistance to indinavir has been reported with the K7R, I54M, I82L/F, V62A-L99F, and L90M mutations; our study provides an in vivo correlation for this observation. 2009 Clinical infectious diseases Discussion HIV I54M;I82F;I82L;K7R;L90M;L99F;V62A 67;73;73;62;96;86;81 71;79;79;65;100;90;85 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. reported selection for L99F by indinavir and nelfinavir in HIV-2 group A strains in culture. 2009 Clinical infectious diseases Discussion HIV L99F 23 27 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. reported that introducing L99F to HIV-2 ROD (group A) strains had no effect on lopinavir or saquinavir resistance in a yeast system. 2009 Clinical infectious diseases Discussion HIV L99F 26 30 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. reported that K7R and L99F mutations occur more commonly during PI treatment, and Ntemgwa et al. 2009 Clinical infectious diseases Discussion HIV K7R;L99F 14;22 17;26 PI 64 66 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The high prevalence (43% of patients; 83% of those with strains with ARV resistance) of the RT mutation M184V, which confers high-level resistance to 3TC and FTC, likely reflects the near universal use of 3TC as a first-line ARV for HIV-2 infection in Senegal. 2009 Clinical infectious diseases Discussion HIV M184V 104 109 RT 92 94 HIV infections 233 248 19143530 Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. The K65R mutation was also observed in virus strains from 17% of patients infected with NRTI-resistant virus and has been associated with resistance to 3TC and FTC. 2009 Clinical infectious diseases Discussion HIV K65R 4 8 NRTI 88 92 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Based on standard genetic sequencing of HIV-1 RNA from plasma of treated patients, K65R and M184V can emerge in subtype C as in B viruses after therapeutic failure with ABC, ddI, TFV and d4T when combined with 3TC. 2009 Retrovirology Discussion HIV K65R;M184V 83;92 87;97 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Further virological tests, including competition assays, are warranted in order to detect more subtle effects of the K65R mutation in subtype C. 2009 Retrovirology Discussion HIV K65R 117 121 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Hence, the overall effect of K65R in subtype C is to reduce susceptibility to TFV. 2009 Retrovirology Discussion HIV K65R 29 33 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. In the absence of biochemical evidence of an enzyme-dependent mechanism for the preferential emergence of K65R in HIV-1 subtype C, the possibility of a template-dependent mechanism is favoured as described by our laboratory elsewhere. 2009 Retrovirology Discussion HIV K65R 106 110 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Natural polymorphisms within subtype C RT did not alter either the direction or the magnitude of the effect of the resistance mutations K65R and M184V. 2009 Retrovirology Discussion HIV K65R;M184V 136;145 140;150 RT 39 41 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Newer backbones (TFV/FTC and ABC/3TC) typically select for the K65R and M184V mutations in HIV-1 subtype B, but these mutations have also frequently emerged in subtype C viruses treated with d4T/3TC. 2009 Retrovirology Discussion HIV K65R;M184V 63;72 67;77 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Our experiments have revealed that subtype C HIV-1 RT has similar enzymatic activity to subtype B RT, and that the K65R and K65R+M184V mutations, affect subtype C RT function in a manner similar to that seen with subtype B RT. 2009 Retrovirology Discussion HIV K65R;K65R;M184V 115;124;129 119;128;134 RT;RT;RT;RT 51;98;163;223 53;100;165;225 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Specific effects include: 1) The efficiency of ssDNA synthesis and initiation is reduced; 2) At low dNTP concentration, K65R RT exhibited lower activity in single-cycle processivity assays while the K65R+M184V mutant showed diminished processivity independent of dNTP concentration. 2009 Retrovirology Discussion HIV K65R;K65R;M184V 120;199;204 124;203;209 RT 125 127 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. Studies with both SIV and a RT SHIV in macaques treated with TFV monotherapy showed selection of the K70E and K65R mutations. 2009 Retrovirology Discussion HIV K65R;K70E 110;101 114;105 RT 28 30 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The finding that both K65R and K65R/M184V decrease the enzymatic fitness of RT in subtype C HIV and that both restore susceptibility to ZDV in an additive manner is important in view of the ongoing switch in use of NRTI backbones away from thymidine analogs and the higher frequency of K65R in subtype C isolates from African patients. 2009 Retrovirology Discussion HIV K65R;K65R;K65R;M184V 22;31;286;36 26;35;290;41 NRTI;RT 215;76 219;78 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. The K65R mutation is located in the fingers domain of RT and its effect on reduction of NRTI incorporation and reduced excision is probably due to an increased rigidity of the active site and effective trapping of the dinucleoside tetraphosphate excision product. 2009 Retrovirology Discussion HIV K65R 4 8 NRTI;RT 88;54 92;56 19210791 Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance. We also confirm that the biochemical basis for the HIV-1 fitness loss that results from the acquisition of the K65R and K65R/M184V mutations are also valid in HIV-1 subtype C RT. 2009 Retrovirology Discussion HIV K65R;K65R;M184V 111;120;125 115;124;130 RT 175 177 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. In one study, CRF02_AG isolates were more susceptible to nelfinavir and ritonavir than other subtypes (associated with K70R in protease); in the other study, subtype C isolates were hypersusceptible to lopinavir (associated with I93L). 2009 AIDS (London, England) Discussion HIV I93L;K70R 229;119 233;123 PR 127 135 19276794 Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda. One report described a CRF01_AE isolate with reduced NNRTI susceptibility (associated with I135T) and two CRF02_AG isolates with reduced susceptibility to abacavir (associated with D123N plus I135V). 2009 AIDS (London, England) Discussion HIV D123N;I135T;I135V 181;91;192 186;96;197 NNRTI 53 58 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Finally, G190A could be present in a very small frequency in the mother's viral quasispecies, below the detection limit of the assays. 2009 PloS one Discussion HIV G190A 9 14 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. G190A is known to impact only slightly in viral fitness, and could have remained in the quasispecies until selected as a major variant by the emergence of T215F and NRTI selective pressure. 2009 PloS one Discussion HIV T215F;G190A 155;0 160;5 NRTI 165 169 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. have shown that certain NRTI mutations, including T215Y, can increase the fitness of K101E+G190S variants. 2009 PloS one Discussion HIV G190S;K101E;T215Y;G190S;K101E;T215Y 92;86;51;91;85;50 97;91;56;96;90;55 NRTI 24 28 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. K101E mutation can cause resistance to nevirapine and a low level resistance to efavirenz and etravirine. 2009 PloS one Discussion HIV K101E 0 5 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. Our standard genotyping showed that K101E was already present in the first sample of the child (before treatment) but only the minority of the virus population had the NNRTI major mutation G190A. 2009 PloS one Discussion HIV G190A;K101E 189;36 194;41 NNRTI 168 173 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The child HIV variant evolved shortly after treatment with 2 NRTIs to a predominant species also carrying the G190A mutation, which confers resistance to all NNRTI, albeit in the absence of NNRTI selective pressure. 2009 PloS one Discussion HIV G190A 110 115 NNRTI;NNRTI;NRTI 158;190;61 163;195;66 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The fact that G190A was not observed in the mother's genotyping may suggest that it could have emerged de novo in the backbone containing K101E during evolution of the child quasispecies. 2009 PloS one Discussion HIV G190A;K101E 14;138 19;143 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The fitness of variants containing solely the K101E mutation remains to be determined but its persistence in the child along all her follow-up and our phylogenetic evidences suggest that this variant was the founder species transmitted to the child even though it was present in less than 0.3% of the mother's viral quasispecies. 2009 PloS one Discussion HIV K101E 46 51 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. The standard genotyping was able to detect G190A mutation only one month after start of ARV, when the T215F mutation was already present (Table 1). 2009 PloS one Discussion HIV G190A;T215F 43;102 48;107 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. We have reported here the description of MTCT of a minor HIV-1 variant carrying the NNRTI mutation K101E. 2009 PloS one Discussion HIV K101E 99 104 NNRTI 84 89 19277127 Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child. We speculate that T215F has emerged in those viral species already carrying both NNRTI mutations, and the selective pressure of NRTI in the child propitiated the emergence of G190A-containing strains as major variants. 2009 PloS one Discussion HIV G190A;T215F 175;18 180;23 NNRTI;NRTI 81;128 86;132 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. A recent study showed that I5L mutants have reduced infectivity and viral replication. 2009 AIDS (London, England) Discussion HIV I5L 27 30 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. For example, epitope variants RQANFLGKI (RI9c) and RQANFLGRI of B*1302 contain positively selected variants arginine or lysine (K4R) at position 8. 2009 AIDS (London, England) Discussion HIV K4R 128 131 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. The B*1302-restricted epitope that overlaps the I5L region exhibits mixed characteristics of both types I and II epitopes, depending on the patient. 2009 AIDS (London, England) Discussion HIV I5L 48 51 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. The mutation at position 5 from isoleucine to leucine is a conserved substitution, suggesting that the functional conservation of this residue is important for the virus. 2009 AIDS (London, England) Discussion HIV I5L 25 53 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Three type II A*30 epitopes overlap the positively selected residue P7S. 2009 AIDS (London, England) Discussion HIV P7S 68 71 19287301 Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer protein of HIV-1 gag. Two type II A*7401-restricted epitopes were identified in this study, both overlapping the positively selected residue S9N. 2009 AIDS (London, England) Discussion HIV S9N 119 122 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Comparison of recombinant viruses carrying whole patient-derived Gag sequences together with their cognate PR and RT sequences (BS viruses) with recombinant viruses carrying patient-derived PR and RT only (XS viruses) revealed a remarkable contribution of Gag cleavage site mutations A431V and I437V in the NC-SP2-p6 region to the emergence of PI resistance in vivo (Table 1). 2009 PLoS pathogens Discussion HIV A431V;I437V 284;294 289;299 SP2;Gag;Gag;NC;Gag;PI;PR;PR;RT;RT 310;65;256;307;314;344;107;190;114;197 313;68;259;309;316;346;109;192;116;199 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. In contrast, the impact of the cleavage site mutations A431V or I437V on viral RC was more nuanced. 2009 PLoS pathogens Discussion HIV A431V;I437V 55;64 60;69 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. In our experiments, the dramatic effects of mutation A431V on resistance, its context-dependent impact on RC, and its strong influence on the ratio of NC to NC-SP2, strongly argues in favor of a critical role of this cleavage event in vivo, in viruses having escaped to pharmacological pressure by protease inhibitors. 2009 PLoS pathogens Discussion HIV A431V 53 58 PR;SP2;NC;NC 298;160;151;157 306;163;153;159 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. The mechanism of this compensation has been documented for mutation A431V, which emerges mostly in viruses carrying resistance mutation V82A in PR. 2009 PLoS pathogens Discussion HIV A431V;V82A 68;136 73;140 PR 144 146 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. The observation that cleavage site mutations A431V and I437V were actually acting as resistance mutations in these highly evolved, highly resistant clinical viruses, is complementary to a recent study, which reported in vitro selection for resistance to an experimental PI using a laboratory strain of HIV-1 leading to emergence of mutations in SP2 at position 436 and 437 before any changes in PR. 2009 PLoS pathogens Discussion HIV A431V;I437V 45;55 50;60 SP2;PI;PR 345;270;395 348;272;397 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. This effect was seen both in the absence or in the presence of inhibitor, consistent with the expectations from the structural analysis of the A431V mutant peptide with wild-type and mutant PR. 2009 PLoS pathogens Discussion HIV A431V 143 148 PR 190 192 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. Upon prolonged treatment, further mutations in Gag outside the cleavage site may render viral RC independent of the A431V or I437V mutations while the effect of these mutations on resistance and thus their selective power in vivo persists. 2009 PLoS pathogens Discussion HIV A431V;I437V 116;125 121;130 Gag 47 50 19300491 Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. We found, however, that adding or removing the NC-SP2 cleavage site mutation A431V in different VIS13-derived clones did have an effect on the amount of fully processed NC relative to its partially cleaved precursor NC-SP2. 2009 PLoS pathogens Discussion HIV A431V 77 82 SP2;SP2;NC;NC;NC 50;219;47;169;216 53;222;49;171;218 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Although the strains examined in their study were comprised of mixed populations of variants, further examination of their data indicates that, in fact, Q151M confers broad-spectrum NRTI resistance both in the presence and in the absence of the V111I substitution. 2009 The Journal of infectious diseases Discussion HIV Q151M;V111I 153;245 158;250 NRTI 182 186 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. concluded that Q151M alone only confers resistance to d4T and ABC and that resistance to other NRTIs involved the coselection of a V111I change in RT. 2009 The Journal of infectious diseases Discussion HIV Q151M;V111I 15;131 20;136 NRTI;RT 95;147 100;149 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. First, in contrast to HIV-1, a single Q151M replacement in HIV-2 RT confers high-level phenotypic resistance to AZT as well as substantial cross-resistance to other nucleoside analogues (table 1). 2009 The Journal of infectious diseases Discussion HIV Q151M 38 43 RT 65 67 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. In contrast, in HIV-2, only 2 amino acid changes (K65R and Q151M or Q151M and M184V) are required for high-level resistance to both of these inhibitors (table 1). 2009 The Journal of infectious diseases Discussion HIV K65R;M184V;Q151M;Q151M 50;78;59;68 55;83;64;73 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. In HIV-1, high-level resistance to both AZT and 3TC typically requires the combination of multiple TAMs, M184V, and additional replacements in RT. 2009 The Journal of infectious diseases Discussion HIV M184V 105 110 RT 143 145 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. In our experiments, we introduced the Q151M change into both an HIV-2ROD-based and an HIV-2UC2-based RT back-ground; both of these strains encode a valine at position 111 of RT. 2009 The Journal of infectious diseases Discussion HIV Q151M 38 43 RT;RT 101;174 103;176 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Our findings lead us to conclude that Q151M alone is sufficient to produce high-level AZT resistance in HIV-2 and that the V111I substitution is not required for broad-spectrum NRTI resistance. 2009 The Journal of infectious diseases Discussion HIV Q151M;V111I 38;123 43;128 NRTI 177 181 19358668 Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. Second, 2 key replacements in the TAM pathway (M41L and T215Y) have no effect on AZT susceptibility in HIV-2 in culture (figure A3 in appendix A, which appears only in the electronic version of the Journal). 2009 The Journal of infectious diseases Discussion HIV M41L;T215Y 47;56 52;61 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Additionally, we found the highest levels of resistance, as defined by at least three TAMs, K65R or 70E, or pan-nucleoside resistance, among those with CD4 cell count less than 100 cells/mul. 2009 AIDS (London, England) Discussion HIV K65R 92 96 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Although in subtype B virus, both thymidine analogs, d4T and ZDV, select for similar TAMs, our data demonstrate that d4T-based initial therapy in patients infected with subtype C virus selects for a broader array of mutations, including the K65R mutation, which may be because of differences in the nucleotide sequence of subtype C virus in this region of reverse transcriptase. 2009 AIDS (London, England) Discussion HIV K65R 241 245 RT 356 377 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. D4T use was associated with the emergence of K65R and K70E mutations in 30% of patients. 2009 AIDS (London, England) Discussion HIV K65R;K70E 45;54 49;58 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. For patients on ZDV, some mutations apparently selected by d4T (K65R, K70E) may have diminished to levels below the limit of detection, resulting in an underestimate in the prevalence of these mutations. 2009 AIDS (London, England) Discussion HIV K65R;K70E 64;70 68;74 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. Higher levels of viral replication and lower CD4 cell counts, possibly related to longer duration of virological failure, are associated with K65R and other non-TAM NRTI mutations. 2009 AIDS (London, England) Discussion HIV K65R 142 146 NRTI 165 169 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. The use of d4T in subtype C virus does not follow predictable patterns in the emergence of mutations and appears to be promiscuous in its ability to select for K65R and K70E (associated with TDF resistance), multiple TAM pathways, Q151M, and T69 insertions. 2009 AIDS (London, England) Discussion HIV K65R;K70E;Q151M 160;169;231 164;173;236 19417582 The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. ZDV use was independently associated with the lack of emergence of these mutations, consistent with observations that K65R increases ZDV sensitivity and TAMs and K65R appear to be antagonistic. 2009 AIDS (London, England) Discussion HIV K65R;K65R 118;162 122;166 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. A371V was observed in the majority of non-B isolates in our cohort (75%) and the Stanford HIV Drug Resistance Database (96% in CRF01_AE). 2009 Antiviral research Discussion HIV A371V 0 5 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Addition of A371V to Type II EEM background conferred cross-resistance to AZT and tenofovir. 2009 Antiviral research Discussion HIV A371V 12 17 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Additionally, results from our cohort establish that the presence of G333E, G335D, V365I or A371V among treatment-naive patients does not play any significant role in the virologic response after initiation of therapies that may, or may not include AZT. 2009 Antiviral research Discussion HIV A371V;G333E;G335D;V365I 92;69;76;83 97;74;81;88 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Although Q509L was not observed in our cohort, this mutation was found in the pretreated patients of another survey (n=118). 2009 Antiviral research Discussion HIV Q509L 9 14 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Although this mutation by itself confers no resistance, it has been reported to contribute to hypersusceptibility to NNRTI as well as resistance to NRTI in the presence of E44A/D and/or EEMs. 2009 Antiviral research Discussion HIV E44A;E44D 172;172 178;178 NNRTI;NRTI 117;148 122;152 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. At present, only N348I has been shown to be involved in resistance to multiple RTIs. 2009 Antiviral research Discussion HIV N348I 17 22 RT 79 83 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. For instance, V118I has been identified in 2% of treatment-naive patients as one of strain-specific polymorphisms, but more frequently observed in RTI-treated patients. 2009 Antiviral research Discussion HIV V118I 14 19 RT 147 150 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Furthermore, the G333D, G335C, N348I, A360I/V and Q509L substitutions were not observed in our cohort, and were also rarely observed among treatment-naive patients (less than 1%) in the Stanford HIV Drug Resistance Database. 2009 Antiviral research Discussion HIV A360I;A360V;G333D;G335C;N348I;Q509L 38;38;17;24;31;50 45;45;22;29;36;55 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. However, site directed mutagenesis studies showed that G333D, G335C, A360I/V and Q509L did not confer significant AZT resistance in the absence of other AZT resistance mutations. 2009 Antiviral research Discussion HIV A360I;A360V;G333D;G335C;Q509L 69;69;55;62;81 76;76;60;67;86 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. However, the A376S polymorphism in samples of treatment-naive patients or in a recombinant virus used in this study conferred mild NVP resistance (Table 2). 2009 Antiviral research Discussion HIV A376S 13 18 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. In our cohort, as well as in the Stanford HIV Drug Resistance Database, we observed a considerable number of treatment-naive clinical samples containing substitutions (E312Q, G333E, G335D, V365I, A371V and A376S) that have been previously associated with AZT resistance. 2009 Antiviral research Discussion HIV A371V;A376S;E312Q;G333E;G335D;V365I 196;206;168;175;182;189 201;211;173;180;187;194 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. In the absence of EEMs, mutations at the connection subdomain of non-subtype B HIV, such as E312N, G335E or A376V, appear to act as simple polymorphisms, because they either maintain or enhance drug susceptibility in non-subtypes B HIV (Table 1). 2009 Antiviral research Discussion HIV A376V;E312N;G335E 108;92;99 113;97;104 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. In this study, the reference clone has an A376T polymorphism that is observed in a wide range of subtypes. 2009 Antiviral research Discussion HIV A376T 42 47 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. None of the isolates in our cohort had the H539N or H549N substitutions which have been proposed to be associated with resistance to NRTIs due to decreasing the frequency of RT template-switching and the level of RNase H activity. 2009 Antiviral research Discussion HIV H539N;H549N 43;52 48;57 NRTI;RT 133;174 138;176 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Our results support the hypothesis that the substitutions observed among treatment-naive patients have little impact on therapeutic outcome by themselves in the absence of AZT-associated mutations, although certain substitutions, such as N348I, A376S, and Q509L, are involved in drug resistance even by themselves. 2009 Antiviral research Discussion HIV A376S;N348I;Q509L 245;238;256 250;243;261 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Q509L confers moderate (~9fold) resistance to NVP (Table 2). 2009 Antiviral research Discussion HIV Q509L 0 5 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Some of these isolates also contain E312V, V365I, A376S/T/P, indicating that at least these substitutions are polymorphisms that preceded any antiviral therapy. 2009 Antiviral research Discussion HIV A376P;A376S;A376T;E312V;V365I 50;50;50;36;43 59;59;59;41;48 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. The Type I EEMs (M41L, L210W, T215Y and occasionally the D67N mutation) appear twice as frequently as Type II EEMs (D67N, K70R, T215F and K219Q mutation) in subtype B, whereas Type II EEMs are mostly observed in non-B isolates. 2009 Antiviral research Discussion HIV D67N;D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 57;116;138;122;23;17;128;30 61;120;143;126;28;21;133;35 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Their increased incidence among NRTI-treated patients as compared to untreated patients (>3-fold, >40-fold and >12-fold increases for G333C, N348I, and A360V respectively [http://hivdb.stanford.edu/cgi-bin/RTPosMutSummary.cgi]) and in the case of Q509L reported by others suggest that they are associated with AZT-resistance. 2009 Antiviral research Discussion HIV A360V;G333C;N348I;Q509L 152;134;141;247 157;139;146;252 NRTI 32 36 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. Therefore, it is unlikely that A376T affects NVP susceptibility. 2009 Antiviral research Discussion HIV A376T 31 36 19428602 Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients. These results indicate that introduction of Q509L may alter virologic responses, especially for NVP, although so far the clinical relevance and virological response of Q509L among the antiretroviral-experienced patients remains to be elucidated by further experiments. 2009 Antiviral research Discussion HIV Q509L;Q509L 44;168 49;173 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. A second positively selected residue in the trans-membrane region V30 also impacts on sensitivity to HIV-1 Vpu, although less dramatically than T45I, when mutated to glycine. 2009 PLoS pathogens Discussion HIV T45I 144 148 Vpu 107 110 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. The observation that a single mutation (T45I) can render tetherin largely insensitive to HIV-1 Vpu mediated degradation is reminiscent of point mutations impacting on APOBEC3G's sensitivity to HIV-1 Vif as well as point mutations in either capsid, TRIM5, TRIMCyp, or Fv1, which strongly impact on sensitivity to restriction. 2009 PLoS pathogens Discussion HIV T45I 40 44 Capsid;Vif;Vpu 240;199;95 246;202;98 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. We also show that the single point mutant T45I is able to render human tetherin resistant to Vpu-mediated cellular depletion, and furthermore that the mechanism involves the proteasome or a ubiquitin-dependent pathway. 2009 PLoS pathogens Discussion HIV T45I 42 46 Vpu 93 96 19461879 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. We hypothesised that the selected changes might impact on sensitivity to viral encoded tetherin countermeasures and in support of this human tetherin becomes largely insensitive to the HIV-1 encoded countermeasure, the Vpu protein, when it is mutated to represent the Tantalus monkey sequence at a single position (T45I). 2009 PLoS pathogens Discussion HIV T45I 315 319 Vpu 219 222 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Of note, variants with Y181C mutations, which are more common in this cohort than K103N mutations, persisted above detection at 12 months posttreatment in over 80% of the women, with little evidence that they declined during this period. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;Y181C 82;23 87;28 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Seventy-five percent of the women in the ZDV/sdNVP arm had viral variants with K103N or Y181C mutations detectable by our allele-specific PCR assay, whereas only 18% of women in the HAART arm had detectable levels of resistant virus (P = 0.007, Tables 2 and 3). 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;Y181C 79;88 84;93 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. The discordance between the results from the different assays used reflects the difference in their sensitivity: the population-based sequencing assay only reliably detects mutations that comprise >20% of the virus population, whereas the K103N and Y181C allele-specific PCR assays detect resistance down to 0.2% and 2%, respectively. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;Y181C 239;249 244;254 19502990 Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Thus, Y181C may be of particular concern in terms of its effect on future treatment options. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Y181C 6 11 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Additionally, the R77Q mutation of Vpr is thought to be associated with long-term control of HIV infection. 2009 PloS one Discussion HIV R77Q 18 22 Vpr 35 38 HIV infections 93 106 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. If preservation of IL-12 expression is associated with the LTNP phenotype, R77Q was a good candidate for testing in the IL-12 secretion assay. 2009 PloS one Discussion HIV R77Q 75 79 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. It is therefore possible to envision that strains of HIV encoding R90K have lower virulence. 2009 PloS one Discussion HIV R90K 66 70 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. It would be of interest to explore whether the R90K amino acid substitution causes disruption of the Vpr dimeric structure. 2009 PloS one Discussion HIV R90K 47 51 Vpr 101 104 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. None of the amino acids reported in this position tested in our assay relieve IL-12 suppression and the R90K substitution is the only substitution which restored the Il-12 secretion profile. 2009 PloS one Discussion HIV R90K 104 108 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Our study uncovers the mechanism of how the R90K substitution allows for IL-12 secretion in the DCs.The R90K substitution perhaps is recognized as a defect and directs Vpr for rapid degradation. 2009 PloS one Discussion HIV R90K;R90K 44;104 48;108 Vpr 168 171 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Reports of the R90K substitution were found by a manual search of the literature and in both cases this mutation was isolated from a patient exhibiting an LTNP phenotype. 2009 PloS one Discussion HIV R90K 15 19 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. The analysis revealed that other amino acid substitutions such as R90G and R90S are present, but at a cumulative frequency not exceeding 1.3%. 2009 PloS one Discussion HIV R90G;R90S 66;75 70;79 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. The deletion of the last three amino acids did not change the ability of Vpr to modulate IL-12 secretion, however, the R90K substitution revealed complete reversal of IL-12 suppression, restoring the level to that observed with the truncation of the entire C-terminal Vpr domain. 2009 PloS one Discussion HIV R90K 119 123 Vpr;Vpr 73;268 76;271 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. The R90K substitution relieves IL-12 suppression and is selected against, since other amino acids more distantly related to R than K are observed in infected subjects. 2009 PloS one Discussion HIV R90K 4 8 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. This would suggest that the R90K substitution is not directly involved in activation of the IL-12 secretion pathway; rather the R90K substitution alleviates the suppressive effect of wild-type and other amino acids found in this position through the reduction of intracellular Vpr protein levels. 2009 PloS one Discussion HIV R90K;R90K 28;128 32;132 Vpr 277 280 19516896 The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. Virus encoding Vpr R90K may be unable to block IL-12 secretion. 2009 PloS one Discussion HIV R90K 19 23 Vpr 15 18 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. 3TC, EFV and NVP have a low genetic barrier towards resistance and it is therefore not unexpected that, in accordance with the results of other studies, the 3TC mutation M184V and the NNRTI mutations K103N, 190G and 181C are frequently observed in case of treatment failure. 2009 AIDS research and therapy Discussion HIV K103N;M184V 200;170 205;175 NNRTI 184 189 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. However, the selection of K65R under a d4T containing regimen seems to be more common among non-B subtypes as observed by others. 2009 AIDS research and therapy Discussion HIV K65R 26 30 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. However, this was mainly among patients receiving a TDF containing regimen which is known to induce the K65R mutation. 2009 AIDS research and therapy Discussion HIV K65R 104 108 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. K65R mutations have previously been described among populations with similar subtypes. 2009 AIDS research and therapy Discussion HIV K65R 0 4 19531211 Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya. The high percentage (62.5%) of patients with a combination of M184V mutations and at least one NNRTI resistance associated mutation, as well as the selection of the broad NRTI cross-resistance mutations Q151M and K65R in 3 patients are worrying. 2009 AIDS research and therapy Discussion HIV K65R;M184V;Q151M 213;62;203 217;67;208 NNRTI;NRTI 95;171 100;175 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Although no K103N mutation, expected to have the most impact on the use of NNRTIs, was seen in the naive samples, there were 2 individuals (1.6%) each with a single mutation (Y181C and G190E) that would have some impact on NNRTI susceptibility. 2009 Antiviral therapy Discussion HIV G190E;K103N;Y181C 185;12;175 190;17;181 NNRTI;NNRTI 75;223 81;228 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Doualla-Bell noted that d4T also selected for K65R in subtype C virus in Botswana, and that the mutation developed within 3 months of tenofovir therapy, unlike in subtype B where the K65R tends to emerge slowly in a small proportion of individuals on tenofovir. 2009 Antiviral therapy Discussion HIV K65R;K65R 46;183 50;187 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Due to the unexpected emergence of the K65R mutation in a substantial proportion of the cohort, tenofovir should be introduced cautiously with careful assessment of its impact on the emergence of resistance. 2009 Antiviral therapy Discussion HIV K65R 39 43 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. It is also possible that 3TC may select for the K65R mutation as recently described.With the registration of tenofovir in South Africa in 2007, there is a push for the widespread use of this agent to replace d4T, initially in those experiencing adverse effects, but with the view to broad-spectrum first-line use. 2009 Antiviral therapy Discussion HIV K65R 48 52 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Other mutations that are more likely to impact on the future use of a protease inhibitor, including D30N, M46I, I47V, I50V and V82A/F, were present, but in a minority of individuals, with only a single mutation noted per individual. 2009 Antiviral therapy Discussion HIV D30N;I47V;I50V;M46I;V82A;V82F 100;112;118;106;127;127 104;116;122;110;133;133 PR 70 78 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Resistance to both NNRTIs and 3TC (M184V) develops rapidly after initial virological breakthrough. 2009 Antiviral therapy Discussion HIV M184V 35 40 NNRTI 19 25 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The impact of these on viral drug susceptibility is uncertain, but many, including L10I/V, K20R, M36I, L63P, A71V/T and V77I, are not expected to cause major drug resistance. 2009 Antiviral therapy Discussion HIV A71T;A71V;K20R;L10I;L10V;L63P;M36I;V77I 109;109;91;83;83;103;97;120 115;115;95;89;89;107;101;124 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The increased presence (9%) of the K65R mutation in the non-naive samples was unexpected, given the absence of abacavir or tenofovir in the South African treatment regimens. 2009 Antiviral therapy Discussion HIV K65R 35 39 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. The two mutations that are likely to reduce susceptibility to NRTIs if transmitted, T215C and M41L, were not seen in either the naive or non-naive groups. 2009 Antiviral therapy Discussion HIV M41L;T215C 94;84 98;89 NRTI 62 67 19578237 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. There is emerging evidence that non-subtype B virus may have a propensity to develop the K65R more readily compared to subtype B. 2009 Antiviral therapy Discussion HIV K65R 89 93 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Another mutation, L289K in p66 subunit, has also been reported to be able to abrogate dimerization. 2009 PloS one Discussion HIV L289K 18 23 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Another report has suggested that two mutations in RT, L234D and W239A, led to premature cleavage of the Gag-Pol precursor and reduced levels of viral enzymes in the virions. 2009 PloS one Discussion HIV L234D;W239A 55;65 60;70 GagPol;RT 105;51 112;53 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. have reported that mutations of W401L and W401A in RT can inhibit RT dimerization, resulting in reduced steady-state level of the RT subunits p66 and p51 in viral lysate, while Gag-Pol was not affected. 2009 PloS one Discussion HIV W401A;W401L 42;32 47;37 GagPol;RT;RT;RT 177;51;66;130 184;53;68;132 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. It was further found that the Pr160gag-pol was indeed incorporated into the virions of these two mutants, because except for RT, all other products of Pr160gag-pol including p24, protease and integrase, could be detected in the viral particles of mutants Y271A and I271A. 2009 PloS one Discussion HIV I271A;Y271A 265;255 270;260 IN;PR;Pol;Pol;p24;PR;PR;RT 192;179;39;160;174;30;151;125 201;187;42;163;177;32;153;127 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Our results also excluded that the mutations of Y271A and I271A affected the cleavage of the Gag-Pol precursor. 2009 PloS one Discussion HIV I271A;Y271A 58;48 63;53 GagPol 93 100 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Our results have also indicated that Y271A and I274A substitutions may change the conformation of RT, leading to oligomerization. 2009 PloS one Discussion HIV I274A;Y271A 47;37 52;42 RT 98 100 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Our results showed that Pr160gag-pol was properly expressed and transported in cells transfected with mutant constructs, Y271A and I271A. 2009 PloS one Discussion HIV I271A;Y271A 131;121 136;126 Pol;PR 33;24 36;26 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. Since it has been reported that bacterially expressed Y271A mutant has only 1% activity of wild type enzyme, we asked whether the mutants would similarly affect RT activity in the viral particles. 2009 PloS one Discussion HIV Y271A 54 59 RT 161 163 19578544 The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability. The replication of two mutants, Y271A and I271A, were found to be almost completely abolished. 2009 PloS one Discussion HIV I271A;Y271A 42;32 47;37 19583845 Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania. All 14 had a combination of M184I/V, conferring resistance to lamivudine, with one or more of K103N, Y181C and G190A, conferring resistance to NNRTIs. 2009 BMC infectious diseases Discussion HIV G190A;K103N;M184I;M184V;Y181C 111;94;28;28;101 116;99;35;35;106 NNRTI 143 149 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. 2/53 (3.8%) patients on stavudine and lamivudine developed K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 59 63 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. A strong correlation between K65R and S68G was observed in a previous study by Trotta et al. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;S68G 29;38 33;42 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. All of these mutations were significantly more prevalent than among patients without K65R and significantly more prevalent among patients on non-TDF containing regimens. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 85 89 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. An important observation in our analysis was the relative absence of TAMS in most of our patients with the K65R mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 107 111 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. and may be one of the steps in the mutational pathway towards Q151M mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Q151M 62 67 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Because K65R does in fact confer significant resistance to TDF-containing regimens, the rate of development of this drug resistant mutation may have significant implications for ART international guidelines, where TDF is frequently reserved for second-line use. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 8 12 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Deletions have been shown to occur most commonly in association with the Q151M complex. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Q151M 73 78 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Factors associated with the presence of K65R included viral load at virologic failure and duration of ART. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 40 44 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Finally, a diverse number of HIV-1 subtypes were observed in our patients; however, due to small patient numbers it is not possible to determine whether there was preferential selection of K65R in one particular subtype or another. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 189 193 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. First, our cohort of patients with the K65R mutation was small, which makes it difficult to draw conclusions about the significance of this mutation, its impact on future therapies, and whether patterns of co-existing mutations are significantly different compared to those in patients without K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R 39;294 43;298 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Further study is therefore needed to assess the exact prevalence of K65R among patients on non-TDF containing ART in resource limited settings and their impact on future therapies. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 68 72 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. In conclusion, a significantly high rate of K65R was observed among patients infected with predominantly CRF02_AG and G HIV-1 subtypes on first-line ART, in this West African setting. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 44 48 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. In general, drug resistance mutations most frequently observed were similar to those described in patients infected with HIV subtype B; however, a notable finding was the significant proportion of patients in this cohort with the K65R mutation, a number of whom had no previous exposure to TDF or other antiretroviral drugs commonly known to select for K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R 230;353 234;357 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. In most published studies, the M184V has occurred in association with K65R; although other studies have observed that the presence of M184V may actually be protective for the development of K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R;M184V;M184V 70;190;31;134 74;194;36;139 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. In our patient population, with a G or CRF02_AG background, the T69 deletion appeared in association with K219R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K219R 106 111 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. In subtype B, it has been reported to occur in close association with S163I. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV S163I 70 75 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. In the study by Sungkanuparph et al., the K65R mutation was observed in 8/122 (7%) failing patients on a first line regimen of fixed dose stavudine, lamivudine and nevirapine which was provided by the Thailand national government. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 42 46 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. It should be noted that in a previous study of resistance mutations associated with similar first line regimens, higher viral loads at the time of virological failure detection were associated with the K65R mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 202 206 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Novel NRTI mutation patterns were also detected in our patient cohort with K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 75 79 NRTI 6 10 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. of a cohort of Malawian patients, 10/52 (5%) patients failing first line stavudine or zidovudine plus lamividine and nevirapine or efavirenz developed the K65R mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 155 159 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Other common mutations that occurred in our patient cohort included the S68G mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV S68G 72 76 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Prior studies with HIV-1 subtype B have demonstrated a strong association between K65R and Q151M. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;Q151M 82;91 86;96 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Recently the rare association between TAMS and K65R was confirmed in vivo; furthermore when K65R was present with TAMS it was only found on the same genome with T215F/Y and >=2 other TAMS in the presence of Q151M. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R;Q151M;T215F;T215Y 47;92;207;161;161 51;96;212;168;168 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Selection of K65R by stavudine, which was part of initial ART in all but one of the patients on non-TDF containing regimens, has been described previously in patients with HIV-1 subtype B. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 13 17 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The absence of TAMs with the K65R mutation has been previously reported. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 29 33 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The combination of K65R and Q151M mutations has also been observed more frequently among patients on non-TDF containing ART, suggesting that this particular resistance pattern may be linked to MDR more specifically than to TDF. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;Q151M 19;28 23;33 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The development of K65R among patients on non-TDF ART is uncommon, especially among patients on first line combinations commonly used in resource limited settings (stavudine or zidovudine plus lamividine and nevirapine or efavirenz). 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 19 23 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The effect of K65R on responses to second line regimens has yet to be fully ascertained. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 14 18 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The K65R has also been observed in two studies conducted in Botswana and South Africa of patients infected with HIV-subtype C on stavudine containing regimens. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 4 8 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The K65R mutation was noted to develop in 2/301 patients (0.7%) in the stavudine containing arm. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 4 8 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The mutation S68G was also found in high frequency in conjunction with K65R in a study by Boucher et al. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;S68G 71;13 75;17 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The number of patients in our cohort where this mutation occurred simultaneously with the K65R was notable, even though it was less frequent than in patients without the K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R 90;170 94;174 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The presence of K65R in these situations may limit the success of TDF containing second-line therapies, particularly in settings where routine genotypic testing is not available and the choice of ART is limited. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 16 20 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The prevalence of 2 or more TAMS was significantly higher among patients lacking the K65R mutation compared to those with the K65R mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R 85;126 89;130 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The Q151M complex, a set of mutations known to confer multi-NRTI resistance, occurred exclusively among patients in this group. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Q151M 4 9 NRTI 60 64 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The route of K65R acquisition among our patients on non-TDF ART is unknown. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 13 17 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. The successful short-term response to second line therapy observed among these patients is likely due to the inclusion of zidovudine in the majority of the second line regimens to which K65R viruses are exquisitely susceptible, as well as the effect of lopinavir/ritonavir. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 186 190 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. They included the Q151M complex, the T69 deletion, K219R and S68G mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K219R;Q151M;S68G 51;18;61 56;23;65 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. This may explain why it was seen more frequently among patients on non-TDF ART; those in whom the Q151M complex mutation also predominated. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Q151M 98 103 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. To our knowledge, only two other studies have reported K65R developing in patients on these antiretroviral combinations in resource limited settings. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 55 59 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. To support these observations, in 23/24 patients in our cohort on TDF-containing ART, Q151M was not present. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Q151M 86 91 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Transmission of the K65R mutation remains rare, especially in resource limited settings. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 20 24 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Twenty-one of the patients in our cohort of 37 patients (56.8 %) with K65R had the M184V mutation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;M184V 70;83 74;88 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. Two in-vitro studies have demonstrated a preferential selection for K65R among HIV-1 subtype C viruses following exposure to didanosine/stavudine and TDF/lamivudine/didanosine; however some clinical data does not indicate a higher in vivo selection for K65R. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R 68;253 72;257 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. which examined the frequency of K65R in a large genotype database, there was a strong negative association between TAMS and K65R with in vitro confirmation of bidirectional phenotypic antagonism. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;K65R 32;124 36;128 19644383 Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. which investigated the in vitro pathways of acquisition of resistance to stavudine in a panel of viruses, the K65R mutation was selected for by stavudine in 7 of 9 viruses under investigation. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 110 114 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. A few potentially relevant IAS-DRMs (e.g., the NRTI mutation, E44D) are not included in the more parsimonious SDRM list. 2009 Antiviral therapy Discussion HIV E44D 62 66 NRTI 47 51 19704170 Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. Given the proven efficacy, cost savings, and the availability of fixed-dose, once-daily cART utilizing NNRTIs, the frequency of mutations affecting this class - especially the 8% overall prevalence of K103N - significantly restricts therapeutic options available to the newly infected. 2009 Antiviral therapy Discussion HIV K103N 201 206 NNRTI 103 109 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Although current recommendations support using a boosted PI for treating patients with transmitted NNRTI resistance, our study suggests that further investigation of etravirine for the treatment of patients primarily infected with a K103N-containing virus is warranted. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 233 238 NNRTI;PI 99;57 104;59 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Consistent with other studies, we found that K103N - particularly K103N alone - was the most common pattern of transmitted genotypic NNRTI resistance, occurring in approximately 3.0% of all new infections. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;K103N 45;66 50;71 NNRTI 133 138 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. For example, in patients developing the nevirapine-resistance mutation Y181C, salvage therapy with efavirenz (which retains high levels of activity against viruses with Y181C) is often ineffective because the virus quasispecies in such patients often contains multiple other NNRTI-resistance mutations (such as K103N) at low levels that may not be detectable by SGRT. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;Y181C;Y181C 311;71;169 316;76;174 NNRTI 275 280 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. For example, PID 8048 had the NRTI-resistance mutation K65R and the accessory NNRTI-resistance mutation P225H and PID 30062 contained the NRTI-resistance mutations M184V, L210W, T215Y, and K219Q. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K219Q;K65R;L210W;M184V;P225H;T215Y 189;55;171;164;104;178 194;59;176;169;109;183 NNRTI;NRTI;NRTI 78;30;138 83;34;142 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. However, the numbers of patients in that study were insufficient to recommend the use of etravirine rather than a ritonavir-boosted PI in patients with K103N. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 152 157 PI 132 134 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. In contrast, in NNRTI-experienced patients in whom SGRT detects only K103N, UDPS often detects additional major NNRTI-resistance mutations. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 69 74 NNRTI;NNRTI 16;112 21;117 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Nonetheless, minority variants were occasionally present in those with transmitted K103N. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 83 88 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. Patients in TMC125-227 whose viral sequences had K103N generally responded to therapy with etravirine plus two NRTIs. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 49 54 NRTI 111 116 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The lower RNA levels among NNRTI-treated patients may be a consequence of the ongoing activity of other drugs in the patients' regimens and possibly the incomplete phenotypic resistance associated with K103N alone (at least to efavirenz). 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 202 207 NNRTI 27 32 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The presence of multiple additional NNRTI-resistance mutations in patients with acquired K103N is consistent with the low genetic barrier to resistance associated with the first generation NNRTIs. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 89 94 NNRTI;NNRTI 36;189 41;195 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. The relative absence of minority drug-resistance variants in ARV-naive patients with K103N is consistent with the transmission bottleneck that occurs at the time of initial HIV-1 infection and the absence of ongoing selective drug pressure following virus transmission. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 85 90 19734799 Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors. This study shows that ARV-naive HIV-1-infected patients in whom SGRT detects the NNRTI-resistance mutation K103N are generally not co-infected with minority variants containing other major NNRTI-resistance mutations such as those that confer etravirine resistance. 2009 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 107 112 NNRTI;NNRTI 81;189 86;194 HIV infections 32 46 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. Efavirenz is principally metabolized by CYP2B6 and the 516G > T single nucleotide polymorphism is associated with elevated efavirenz levels. 2009 The Journal of antimicrobial chemotherapy Discussion HIV G516T 55 63 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. Efavirenz resistance mutations developed in 6%-8% of patients treated with efavirenz plus two NRTIs for 2-3 years, with the K103N reverse transcriptase mutation being by far the most common single mutation. 2009 The Journal of antimicrobial chemotherapy Discussion HIV K103N 124 129 RT;NRTI 130;94 151;99 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. Efavirenz was also associated with more mutations associated with resistance to two drug classes and more K65R mutations than boosted lopinavir. 2009 The Journal of antimicrobial chemotherapy Discussion HIV K65R 106 110 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. G190A, Y181C and K101E) while only 1.1% had four or more such mutations. 2009 The Journal of antimicrobial chemotherapy Discussion HIV K101E;Y181C;G190A 17;7;0 22;12;5 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. In the A5005S trial, patients were randomized to receive efavirenz, nelfinavir or both, combined with zidovudine plus lamivudine or didanosine plus stavudine. 2009 The Journal of antimicrobial chemotherapy Discussion HIV A5005S 7 13 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. Patients with the 983T > C polymorphism at position CYP2B6 also have increased levels of efavirenz. 2009 The Journal of antimicrobial chemotherapy Discussion HIV T983C 18 26 19767318 Efavirenz: a decade of clinical experience in the treatment of HIV. The principal mutation selected by efavirenz:K103M:does not confer resistance to efavirenz, while the primary mutation selected during nevirapine therapy (Y181C) does confer efavirenz resistance. 2009 The Journal of antimicrobial chemotherapy Discussion HIV K103M;Y181C 45;155 50;160 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. One of these mutations, R69H (DH), gives a broad-specificity TRIMCyp that can bind and restrict viruses from both lentiviral lineages. 2009 Nature structural & molecular biology Discussion HIV R69H 24 28 19767750 Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. The second mutation, D66N (NR) completes the retargeting by making a potent HIV-2 restriction factor at the cost of the loss of HIV-1 specificity. 2009 Nature structural & molecular biology Discussion HIV D66N 21 25 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. 4) has shown that T215Y significantly contributes to the binding of ATP to the mutant RT for excision by stacking with its adenine base and K70R forms a network of hydrogen-bonding interactions with the alpha'-phosphate and 3'-OH of ATP.4 The K65R mutation has the opposite effect of decreasing the rate of excision due in part to the K65R/Arg72 platform-based conformational constraints. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R;K70R;T215Y 243;335;140;18 247;339;144;23 RT 86 88 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. 5) suggests that the constraint on Arg72 caused by the K65R mutation (via the K65R/Arg72 platform) and the alteration of the adjacent molecular surface by the L74V mutation removes the support for the template base proximal to where it is base-paired with the dNTP (supplemental. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R;L74V 55;78;159 59;82;163 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. An alpha-boranophosphate-modified ddATP, however, incorporates slightly more efficiently than dATP for K65R RT. 2009 The Journal of biological chemistry Discussion HIV K65R 103 107 RT 108 110 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. As discussed above, this structural difference results in Arg72 having a rotamer-2 conformation in both the wild-type and K65R mutant RT ternary complexes with TFV-DP compared with the common rotamer-1 conformation in the structures of the K65R RT dsDNA dATP, wild-type RT dsDNA dTTP, wild-type RT dsDNA AZTppppA, and TAM RT dsDNA AZTppppA complexes,4 all of which have superimposable deoxyribose rings. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R 122;240 126;244 RT;RT;RT;RT;RT 134;245;270;295;322 136;247;272;297;324 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. As is evident from the current structures, the K65R mutation restricts the adaptability of both the Arg65 and Arg72 side chains via the stacking of guanidinium planes. 2009 The Journal of biological chemistry Discussion HIV K65R 47 51 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. As seen in the dATP-bound K65R RT structure. 2009 The Journal of biological chemistry Discussion HIV K65R 26 30 RT 31 33 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Biochemical and clinical data have shown that K65R has broad phenotypic effects on NRTIs. 2009 The Journal of biological chemistry Discussion HIV K65R 46 50 NRTI 83 88 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Biochemically, K65R RT decreases the rate of incorporation (kpol) of all natural substrates and approved NRTI drugs; the incorporation kinetics of the adenosine analogs dATP, TFV-DP, and ddATP (the active metabolite of ddI) determined by several groups are shown in Table 2. 2009 The Journal of biological chemistry Discussion HIV K65R 15 19 NRTI;RT 105;20 109;22 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Clinically, the K65R resistance mutation develops after treatment with abacavir, ddI, stavudine, and TFV disoproxil fumarate and causes reduced susceptibility to all approved NRTIs with the exception of AZT, where full susceptibility is retained. 2009 The Journal of biological chemistry Discussion HIV K65R 16 20 NRTI 175 180 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Implications for K65R Interactions with Other Resistance Mutations. 2009 The Journal of biological chemistry Discussion HIV K65R 17 21 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. In fact, for all substrates characterized by pre-steady state kinetics, the binding affinity of K65R is minimally affected compared with wild-type RT. 2009 The Journal of biological chemistry Discussion HIV K65R 96 100 RT 147 149 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. In the current K65R structures, one of the guanidinium nitrogens of Arg65 functionally replaces the Nzeta atom of Lys65 by interacting with a gamma-phosphate/beta-gamma-linker oxygen of dNTP (or TFV-DP). 2009 The Journal of biological chemistry Discussion HIV K65R 15 19 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. It is likely that the guanidinium groups of K70R and K65R may stack together and extend the K65R/Arg72 platform to Arg72/K65R/K70R if RT contains both a K65R and a K70R mutation. 2009 The Journal of biological chemistry Discussion HIV K65R;K70R;K65R;K65R;K65R;K70R;K70R 121;126;53;92;153;44;164 125;130;57;96;157;48;168 RT 134 136 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R is surrounded by other residues associated with NRTI resistance and is commonly associated with M184V or Q151M but is negatively associated with others, such as L74V or most TAMs. 2009 The Journal of biological chemistry Discussion HIV L74V;M184V;Q151M;K65R 166;101;110;0 170;106;115;4 NRTI 53 57 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. K65R Mutation and Resistance to TFV. 2009 The Journal of biological chemistry Discussion HIV K65R 0 4 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. L74V is negatively associated with K65R and is positioned underneath the template base that complements the base of the incoming dNTP (supplemental. 2009 The Journal of biological chemistry Discussion HIV K65R;L74V 35;0 39;4 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Mutations that are negatively associated with K65R show unfavorable complementarity with the K65R/Arg72 platform. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R 46;93 50;97 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Our structural results are consistent with biochemical and clinical findings, and the structural analyses further suggest that the K65R mutation discriminates TFV-DP from dATP by locking Arg72 in an alternate conformation (rotamer-2) when TFV-DP is bound. 2009 The Journal of biological chemistry Discussion HIV K65R 131 135 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Several pre-steady state kinetic studies (summarized in Table 2) for dATP, TFV-DP, and ddATP show that the preferential modes of binding of the K65R/Arg72 platform to TFV-DP do not improve or disfavor its binding affinity compared with the natural substrate dATP. 2009 The Journal of biological chemistry Discussion HIV K65R 144 148 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. Significance of the K65R Mutation for RT Function. 2009 The Journal of biological chemistry Discussion HIV K65R 20 24 RT 38 40 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. T215Y is located further away from K65R mutation site; however, the K65R/Arg72 platform is likely to interfere with the positioning of beta'- and gamma'-phosphates of ATP and constrain the conformational mobility of the fingers loop, thus decreasing the efficiency of excision. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R;T215Y 35;68;0 39;72;5 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. TAMs (M41L, D67N, K70R, T215Y/F, and K219Q/E/N) cause enhanced NRTI excision, a major mechanism of resistance where the excision of incorporated nucleotides is mediated by ATP. 2009 The Journal of biological chemistry Discussion HIV D67N;K219E;K219N;K219Q;K70R;M41L;T215F;T215Y 12;37;37;37;18;6;24;24 16;46;46;46;22;10;31;31 NRTI 63 67 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The absence of this interaction network, added to the constraint imposed by the K65R/Arg72 platform, may prevent ddATP from attaining the positioning of the phosphates and the dideoxyribose ring required for optimal incorporation. 2009 The Journal of biological chemistry Discussion HIV K65R 80 84 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The comparison of the interactions of K70R and K65R shows that the two residues interact with ATP, and the positioning of K70R would be affected by the K65R mutation and vice versa. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R;K70R;K70R 47;152;38;122 51;156;42;126 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The decreased rates of the incorporation of dNTPs appear to account for decreased viral replication capacity of the K65R mutant. 2009 The Journal of biological chemistry Discussion HIV K65R 116 120 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The guanidinium groups of Arg65 and Arg72 are stacked in both K65R mutant structures. 2009 The Journal of biological chemistry Discussion HIV K65R 62 66 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The incorporation of TFV-DP, which has a flexible acyclic oxypropyl linker substituted for the ribose ring, is minimally affected by the addition of the beta-branched M184V mutation and K65R-induced platform. 2009 The Journal of biological chemistry Discussion HIV K65R;M184V 186;167 190;172 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R mutation has a more significant effect on incorporation of ddATP than on the incorporation of dATP (Table 2), although the only difference between the two is that ddATP lacks the 3'-OH. 2009 The Journal of biological chemistry Discussion HIV K65R 4 8 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R substitution adds a bulky guanidinium group, which can form additional hydrogen bonds with restricted geometry and can participate in hydrophobic stacking. 2009 The Journal of biological chemistry Discussion HIV K65R 4 8 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The K65R/M184V double mutant has increased resistance to the NRTIs ddI, abacavir, 3TC, and emtricitabine but improved susceptibility to TFV, stavudine, and AZT compared with K65R alone. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R;M184V 4;174;9 8;178;14 NRTI 61 66 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The locked alternate conformation of Arg72 imposed by the K65R mutation in the TFV-DP-bound structure may further restrict Arg72 to attain conformations or an electronic configuration that might be required for the catalytic steps of the polymerization reaction. 2009 The Journal of biological chemistry Discussion HIV K65R 58 62 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The M184V-mediated positional constraints and narrowing at the polymerase active site are consistent with the observed increase in Kd for dNTP binding. 2009 The Journal of biological chemistry Discussion HIV M184V 4 9 Pol 63 73 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The mutations K65R and M184V impose structural restraints on the two sides of the deoxyribose binding site (supplemental. 2009 The Journal of biological chemistry Discussion HIV K65R;M184V 14;23 18;28 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. The structural constraint by the K65R/Arg72 platform may also act like a "checkpoint" that helps discriminate among dNTPs for correct base pairing with the template, which thereby provides a possible explanation for the reported increase in fidelity of the K65R mutant. 2009 The Journal of biological chemistry Discussion HIV K65R;K65R 33;257 37;261 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. These kinetic data correlate with the structural information indicating that the K65R/Arg72 platform would restrain the movements of these residues and hinder the efficiency of nucleotide incorporation/excision. 2009 The Journal of biological chemistry Discussion HIV K65R 81 85 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. This extended platform would add further constraints that may not support adequate RT function and may explain the antagonistic relationship between the K65R and K70R mutations. 2009 The Journal of biological chemistry Discussion HIV K65R;K70R 153;162 157;166 RT 83 85 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. This is most notable for incorporated AZT, where the decreased incorporation of AZT-TP is counteracted by significantly decreased excision after its incorporation that results in full susceptibility of K65R viruses to this NRTI. 2009 The Journal of biological chemistry Discussion HIV K65R 202 206 NRTI 223 227 19812032 Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. which might explain the reduced rate of nucleotide incorporation by K65R mutant RT compared with wild-type RT (Table 2). 2009 The Journal of biological chemistry Discussion HIV K65R 68 72 RT;RT 80;107 82;109 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. A V106M mutation in RT is preferentially selected both in vitro and in vivo by the NNRTI efavirenz in subtype C viruses and confers high-level cross-resistance to all 3 currently approved NNRTIs. 2005 Journal of the International AIDS Society Discussion HIV V106M 2 7 NNRTI;NNRTI;RT 83;188;20 88;194;22 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. However, M184I is rare in clinical samples and the switch from isoleucine to valine results from a A G transition. 2005 Journal of the International AIDS Society Discussion HIV M184I 9 14 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. In RT, V75T which confers resistance to stavudine only occurred in 4% of patients treated with this drug. 2005 Journal of the International AIDS Society Discussion HIV V75T 7 11 RT 3 5 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Of note, some of the common resistance mutations that are easily selected by drugs in vivo and in cell culture involve A G transitions, eg, M184V and Y181C. 2005 Journal of the International AIDS Society Discussion HIV M184V;Y181C 140;150 145;155 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Other mutations resulting from G A transitions may occur rarely, such as V82T (the preferred mutation in this position is V82A, which results from a T C transition). 2005 Journal of the International AIDS Society Discussion HIV V82A;V82T 122;73 126;77 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. Some of the resistance mutations that result from a G A transition confer only low levels of resistance when they appear alone, such as K20R and V32I in PR and D67N and G333A in RT. 2005 Journal of the International AIDS Society Discussion HIV D67N;G333A;K20R;V32I 160;169;136;145 164;174;140;149 PR;RT 153;178 155;180 19825125 Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs. The G A hypermutation is the cause of the M184I substitution which commonly occurs prior to M184V. 2005 Journal of the International AIDS Society Discussion HIV M184I;M184V 42;92 47;97 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. By contrast, the outgrowth of a single clonal subpopulation resistant to both EFV and FTC that resulted in therapeutic failure implies that the K103N population may have been so small that the M184I variant was present at a low frequency at the time of initiation of combination therapy. 2009 Retrovirology Discussion HIV K103N;M184I 144;193 149;198 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. For example, in M03250 at weeks 23 and 25, 6-8 weeks after initiation of combination therapy, 11 of 23 minor subpopulations contained K103N mutations and totaled 25-30% of the entire population. 2009 Retrovirology Discussion HIV K103N 134 139 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. In M03250, at least 4 subpopulations that encode EFV resistance appeared that contained either of the K103N alleles (AAT or AAC). 2009 Retrovirology Discussion HIV K103N 102 107 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. In M04007 V75L was not detected at week 13 and the only V75L subpopulation found in week 17 did not persist or spread to other subpopulations at later time points, suggesting that the selective advantage it confers may be host specific. 2009 Retrovirology Discussion HIV V75L 56 60 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. In our study, V75L appeared before the emergence of any drug resistant mutations, and it spread to almost all subpopulations in later time points. 2009 Retrovirology Discussion HIV V75L 14 18 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. In the two monkeys, M03250 and M04008, this dominant cell supernatant subpopulation was rapidly replaced by new dominant subpopulations (Figures 3 and 5) characterized by the V75L mutation not detected in the inoculum. 2009 Retrovirology Discussion HIV V75L 175 179 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. L214F was reported in previous RT-SHIV studies, although no quantitative analysis was reported. 2009 Retrovirology Discussion HIV L214F 0 5 RT 31 33 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Similarly, a singe clonal population containing both K103N and K65R was present only briefly during combination therapy. 2009 Retrovirology Discussion HIV K103N;K65R 53;63 58;67 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Subpopulations with both K103N alleles were present as early as one week after treatment with EFV in M03250 and M04008. 2009 Retrovirology Discussion HIV K103N 25 30 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The 214F mutation is associated with nucleoside analogue mutation cluster 2 (D67N+K70R+K219Q+T215F) and negatively associated with nucleotide analogue mutation cluster 1 (M41L+L210W+T215Y). 2009 Retrovirology Discussion HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 77;87;82;176;171;93;182 81;92;86;181;175;98;187 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The amount of virus replication prior to week 13 in M04007 may have been too small for any K103N mutants to be present in the replicating population at that time or the frequency of K103N in week 13 was too low to be detected with our sampling size. 2009 Retrovirology Discussion HIV K103N;K103N 91;182 96;187 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The existence of multiple minor subpopulations carrying either K103N AAC or AAT suggests that different subpopulations acquired them independently, rather than from a common ancestor, implying that a large effective population size must have been present pre-therapy. 2009 Retrovirology Discussion HIV K103N 63 68 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. The presence of a variety of RT-SHIV subpopulations containing K103N in M02350 and M04008 following EFV monotherapy (Additional files 1 and 2), which never became dominant, indicates that K103N alone did not confer a growth advantage to the virus in either the presence or absence of therapy. 2009 Retrovirology Discussion HIV K103N;K103N 63;188 68;193 RT 29 31 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. This animal subsequently failed combination therapy, at which time the virus population was characterized by the appearance of viruses with additional mutations, initially K65R (conferring TNF resistance) followed by a clonal subpopulation containing K103N and M184I (conferring FTC resistance), which rapidly became dominant. 2009 Retrovirology Discussion HIV K103N;K65R;M184I 251;172;261 256;176;266 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. This pattern suggests that V75L probably conferred a selective advantage to the virus on its own, rather than being secondary to known drug resistant mutations. 2009 Retrovirology Discussion HIV V75L 27 31 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. V75L appeared in that study after the introduction of the quinoxaline resistant mutation G190Q. 2009 Retrovirology Discussion HIV G190Q;V75L 89;0 94;4 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. We hypothesize that the patterns observed reflect the relative population sizes of productively infected cells in these animals, with higher viremia in M03250 correlating with the presence and selection of multiple subpopulations of K103N variants by EFV monotherapy and the appearance of additional drug resistance mutations (K65R and M184I/V) within the population containing one of the K103N alleles. 2009 Retrovirology Discussion HIV K103N;K103N;K65R;M184I;M184V 233;389;327;336;336 238;394;332;343;343 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. We observed a rapid increase in the frequency of another common polymorphism, L214F, in M03250 from 0% at week 0 to 41% at week 10, and 100% at week 25. 2009 Retrovirology Discussion HIV L214F 78 83 19889213 RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. While V75T causes resistance to dideoxyribonucleoside RT inhibitors, V75L has not been reported to be a drug resistance mutation. 2009 Retrovirology Discussion HIV V75L;V75T 69;6 73;10 RT 54 56 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. Current NMR data demonstrate more pronounced differences in the interaction of the G86 mutants with active-site inhibitors than seen for the R87K mutant. 2010 Proteins Discussion HIV R87K 141 145 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. In contrast to the R87K mutation that reduces the catalytic activity by increasing the dimer dissociation constant, the G86 mutation has a different mechanism to reduce the catalytic activity without severely increasing Kd; mutation of G86 causes a decrease in the dimer interaction with substrate. 2010 Proteins Discussion HIV R87K 19 23 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. The D25N mutant is inactive, being the catalytic residue, and is predominantly a dimer at 20 muM concentration as seen by NMR. 2010 Proteins Discussion HIV D25N 4 8 19899162 Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease. This active-site mutant D25N has been used extensively to study the protease-substrate complex by solution NMR and crystallography. 2010 Proteins Discussion HIV D25N 24 28 PR 68 76 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. The burden of resistance at detection of viremia is consistent with previous studies in which prevalence of NNRTI mutations ranged from 45 to 100%, the M184V/I mutation from 24 to 95%, and any TAM from 0 to 75% . 2009 Clinical infectious diseases Discussion HIV M184I;M184V 152;152 159;159 NNRTI 108 113 19911963 Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. When viremic for an additional 6 months on first-line therapy most patients had an NNRTI resistance mutation and approximately two-thirds had the M184V/I mutation. 2009 Clinical infectious diseases Discussion HIV M184I;M184V 146;146 153;153 NNRTI 83 88 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Based on allele-specific PCR testing, 50% of women treated with three drugs developed the M184V mutation. 2010 AIDS (London, England) Discussion HIV M184V 90 95 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Based on this limited number of subjects, we did not observe an association between pre-existing resistance and the postpartum selection of M184V or K103N. 2010 AIDS (London, England) Discussion HIV K103N;M184V 149;140 154;145 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. In the univariate risk factor analysis, women who had all HIV-1 RNA levels above 400 copies/mL during the study were 2.7 times more likely to have the M184V mutation detected postpartum than those remaining aviremic through delivery. 2010 AIDS (London, England) Discussion HIV M184V 151 156 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Similarly, subjects receiving nelfinavir were 4 times less likely to develop postpartum M184V than those not receiving this drug. 2010 AIDS (London, England) Discussion HIV M184V 88 93 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Similarly, the post-partum detection of the K103N mutation was independently associated with exposure to nevirapine and duration of exposure to zidovudine and lamivudine. 2010 AIDS (London, England) Discussion HIV K103N 44 49 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. These findings suggest that women treated with drugs with high genetic barrier to attain resistance are less likely to develop the M184V mutation. 2010 AIDS (London, England) Discussion HIV M184V 131 136 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Use of dual therapy and duration of zidovudine exposure, which reflects the overall duration of antiretroviral therapy, were the only two variables that were independently associated with an increased risk of M184V detection after delivery. 2010 AIDS (London, England) Discussion HIV M184V 209 214 19915448 Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy. Virtually all women receiving dual therapy developed the M184V mutation. 2010 AIDS (London, England) Discussion HIV M184V 57 62 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Codon 125 has been shown to vary by subtype in other studies; however, we additionally observed that T125A was predicted by HLA-B57/5801 genotypes in subtype B viruses, and therefore showed that a component of the tendency to develop integrase inhibitor resistance is conditioned by host genetics. 2009 Antiviral therapy Discussion HIV T125A 101 106 IN 234 243 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. In the case of HLA-B57/5801 alleles, the greater barriers to immune escape and effect of T125A predict an added protection against integrase inhibitor resistance. 2009 Antiviral therapy Discussion HIV T125A 89 94 IN 131 140 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. In this population-based review of all sites associated with integrase inhibitor resistance in 342 natural isolates of HIV-1 obtained from two geographically distinct cohorts in Switzerland and Australia, we observed that the primary raltegravir and elvitegravir resistance mutations T66I, E92Q, G140S, Y143C/H/R, Q148H/R/K and N155H were absent. 2009 Antiviral therapy Discussion HIV E92Q;G140S;N155H;Q148H;Q148K;Q148R;T66I;Y143C;Y143H;Y143R 290;296;328;314;314;314;284;303;303;303 294;301;333;323;323;323;288;312;312;312 IN 61 70 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. Specific subtype drug resistance interactions have been described in other drug contexts, such as the more rapid selection of RT K65R on tenofovir in subtype C viruses and the low prevalence of nelfinavir-associated D30N in subtype C viruses, among others. 2009 Antiviral therapy Discussion HIV D30N;K65R 216;129 220;133 RT 126 128 19918099 Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance. We focused on T125A as the most prevalent of these mutations. 2009 Antiviral therapy Discussion HIV T125A 14 19 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. Although subtype C isolates have been reported to have a higher tendency to develop K65R, by contrast, we observed a lower rate of K65R when compared with global reports, but a higher rate than that reported in India so far. 2009 Antiviral therapy Discussion HIV K65R;K65R 84;131 88;135 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. Among the NNRTI mutations, Y181C mainly selected among patients failing a regimen containing NVP, and K103N among those failing EFV, as reported earlier. 2009 Antiviral therapy Discussion HIV K103N;Y181C 102;27 107;32 NNRTI 10 15 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. NAMs were observed at a similar frequency between the groups; not surprisingly, M184V was the predominant mutation and its frequency is in agreement with other patients failing HAART and other studies in subtype C globally that included 3TC. 2009 Antiviral therapy Discussion HIV M184V 80 85 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. Prior studies have also found K65R to be associated with patients failing a d4T-containing regimen, which is in line with the findings our study. 2009 Antiviral therapy Discussion HIV K65R 30 34 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. T215Y, L210W and M41L, which constitute the TAM-1 pathway were significantly higher in group B, and this might be associated with their prior AZT/3TC dual therapy prior to HAART. 2009 Antiviral therapy Discussion HIV L210W;M41L;T215Y 7;17;0 12;21;5 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. Unlike the previous reports, Q151M and its accessory mutations were observed among patients exposed to d4T rather than AZT/didanosine (ddI), which could be a result of bias in the number of patients on failing AZT/ddI-containing regimen. 2009 Antiviral therapy Discussion HIV Q151M 29 34 19918105 Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India. V106M was predominant over V106A, as reported previously, for subtype C viruses because the natural GTG polymorphism at codon 106 in clade C variants is distinct from clade B viruses. 2009 Antiviral therapy Discussion HIV V106A;V106M 27;0 32;5 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. As the alpha-helical domains of cytoplasmic domian have been reported to be involved in oligomerization, another possibility is that the L63A mutant is destabilizing the oligomeric structure of Vpu. 2010 Virology Discussion HIV L63A 137 141 Vpu 194 197 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Both the L63A and V68A mutants also had a reduced rate of degradation. 2010 Virology Discussion HIV L63A;V68A 9;18 13;22 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. In their studies, mutation of the conserved leucine at position 63 to a proline or mutation of residues from position 65 to 70 to alanines affected CD4 degradation, without altering Vpu-CD4 interactions. 2010 Virology Discussion HIV L63P 44 79 Vpu 182 185 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Interestingly, the L63A mutant actually resulted in higher levels of CD4 surface expression than non-transfected cells or cells transfected with a control plasmid (pcEGFP). 2010 Virology Discussion HIV L63A 19 23 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. It will be of interest if the L63A mutant is capable of pulling down the Cullin1/Skp1 complex. 2010 Virology Discussion HIV L63A 30 34 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. It will be of interest to determine the effect of the L63A mutation on virus release and on virus pathogenesis using our SHIV/macaque model. 2010 Virology Discussion HIV L63A 54 58 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. None of the mutant proteins functioned as well as wild-type, but L63I and L63G did have partial function, indicating that the length of the side chain is important. 2010 Virology Discussion HIV L63G;L63I 74;65 78;69 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Our results confirm that S61A did not affect CD4 degradation and the turnover of the protein was decreased. 2010 Virology Discussion HIV S61A 25 29 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Our results indicate that like the S61A mutant, the L63A mutant also had a decreased turnover but was different from S61A mutant as L63A severely affected CD4 surface down-modulation. 2010 Virology Discussion HIV L63A;L63A;S61A;S61A 52;132;35;117 56;136;39;121 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. The protein structure programs used in this study showed that L63P resulted in a shorter predicted alpha-helical domain while the substitution of six residues at positions 65-70 extended the alpha-helical domain (data not shown). 2010 Virology Discussion HIV L63P 62 66 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. The V68A mutant also affected CD4 surface expression, but to a lesser degree than the invariant leucine. 2010 Virology Discussion HIV V68A 4 8 19944437 Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. Thus, a salient feature of our study is that the L63A, which does not disrupt the predicted alpha-helical structure, severely affects the ability to down-modulate expression of CD4 from the cell surface. 2010 Virology Discussion HIV L63A 49 53 19949656 Antiretroviral genotypic resistance mutations in HIV-1 infected Korean patients with virologic failure. Almost all patients were taking 3TC in our study group and most isolates of these patients revealed resistance to 3TC associated with M184V/I mutation. 2009 Journal of Korean medical science Discussion HIV M184I;M184V 134;134 141;141 19949656 Antiretroviral genotypic resistance mutations in HIV-1 infected Korean patients with virologic failure. It is known that presence of the M184V mutation might delay or prevent emergence of thymidine analogue mutations (TAM). 2009 Journal of Korean medical science Discussion HIV M184V 33 38 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. By both conventional (PG) and clonal sequencing methods, virus from four of the VF subjects (including the post-VF results of Subject 1) selected TAMs but had no detectable M184V by clonal analysis at their last study visit, and this lack of M184V selection may have resulted in a more rapid selection of multiple TAMs. 2010 The Journal of antimicrobial chemotherapy Discussion HIV M184V;M184V 173;242 178;247 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. For those subjects who met VF criteria and had detectable resistance mutations at failure, TAMs + M184V was the predominant pattern, although a low incidence of K65R was detected. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184V 161;98 165;103 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Furthermore, the HIV-1 from Subject 1, which had selected K65R mutations at VF, continued to evolve under drug selection pressure and, at a post-VF timepoint, two distinct clonal populations emerged, those containing K65R and another that contained TAMs. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K65R 58;217 62;221 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. In the as-treated analysis, 1/40 subjects treated with twice-daily abacavir/lamivudine/zidovudine + once-daily tenofovir experienced VF; virus from this subject also selected for M184V + TAMs (D67N, K70E, T215Y and K219E), and the authors noted that this subject had incomplete regimen adherence. 2010 The Journal of antimicrobial chemotherapy Discussion HIV D67N;K219E;K70E;M184V;T215Y 193;215;199;179;205 197;220;203;184;210 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. In their cross-study comparison, they concluded that this regimen was an efficient treatment strategy in moderately pre-treated patients and that virological success was observed for this regimen in the presence of the M184V mutation and low numbers of TAMs, although the presence of at least two TAMs, especially when the T215Y/F mutation was present, or the L210W mutation alone was a predictor of VF. 2010 The Journal of antimicrobial chemotherapy Discussion HIV L210W;M184V;T215F;T215Y 360;219;323;323 365;224;330;330 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Interestingly, one of the two subjects whose HIV did select for K65R may have been predisposed to selection of the K65R mutation by the presence of the K70E mutation, as low-abundance clones with this mutation were detected at baseline. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K65R;K70E 64;115;152 68;119;156 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K65R was also observed at low incidence (2/14 subjects) at VF in COL40263. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R 0 4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. K70E has been shown in macaques to precede selection for K65R when treated with tenofovir and also to precede selection for K65R in patients when tenofovir, abacavir and lamivudine are co-administered. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K65R;K70E 57;124;0 61;128;4 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. No clone from any of the subjects with VF contained both K65R and T215F or Y mutations. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;T215F 57;66 61;71 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Since tenofovir was administered separately from the co-formulated abacavir/lamivudine/zidovudine, it is also possible that K65R could have emerged through partial adherence to the drug regimen, or that use of zidovudine once daily rather than twice daily was not sufficient in some patients to modulate selection in those patients experiencing VF towards a TAM pathway. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R 124 128 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. Taken as a whole, the data from this study suggest that TAM selection is a preferred resistance route, rather than K65R, when zidovudine is combined with abacavir, lamivudine and tenofovir and is consistent with PG results from in vivo studies in HIV-1-infected antiviral-naive or -experienced subjects treated with this quadruple regimen in which TAMs were more likely to be detected than K65R. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K65R 115;390 119;394 HIV infections 247 261 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The clonal data from this study also suggest that for ART-naive subjects receiving this regimen, the pathway may also be biased towards selection via the 215F pathway, as this regimen was more common than T215Y. 2010 The Journal of antimicrobial chemotherapy Discussion HIV T215Y 205 210 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The K70E mutation also produces slightly less tenofovir resistance, suggesting that under tenofovir selection pressure virus with K65R will have a growth advantage. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K70E 130;4 134;8 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The presence of M184V has been previously associated with a lower incidence of treatment-emergent TAMs independent of time on therapy, suggesting a direct effect of M184V on reduced selection of TAMs. 2010 The Journal of antimicrobial chemotherapy Discussion HIV M184V;M184V 16;165 21;170 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. The role of pre-existing K65R as a predictor of VF for a later treatment regimen with quadruple abacavir/lamivudine/zidovudine + tenofovir therapy was unable to be clearly addressed in the review of Sturmer et al. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R 25 29 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. These included mutations considered to be multidrug resistance-conferring mutations (such as F77L and A62V) that could have provided a replication advantage under drug pressure from which more fit mutations might be selected. 2010 The Journal of antimicrobial chemotherapy Discussion HIV A62V;F77L 102;93 106;97 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. This agrees with the findings of Parikh et al., who have suggested that there is no net evolutionary benefit for the virus to simultaneously select both TAMs and K65R. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R 162 166 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. This antagonism may be a pan-HIV phenomenon, as a similar counterselection for K65R by mutations at T215 in subjects infected with HIV-2 was recently reported. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R 79 83 20008905 Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir. While K70E and K65R are both selected by tenofovir, they appear to be structurally incompatible, and, when both are detected by PG after in vivo treatment with tenofovir, they occur on separate viral genomes. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K70E 15;6 19;10 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. I13 V and E35D often appear during nelfinavir treatment. 2010 AIDS (London, England) Discussion HIV E35D;I13V 10;0 14;6 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. In this study, polymorphisms in the CRF01_AE protease gene were common, with the M36I polymorphism being the most frequent. 2010 AIDS (London, England) Discussion HIV M36I 81 85 PR 45 53 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. Interestingly, R41K and H69K have not previously been reported to be associated with any currently available protease inhibitors, and the predicted HLA binding affinities at the epitope located at amino acid positions 34-42 decreases 19-40 fold when E35D, M36I and R41K are present. 2010 AIDS (London, England) Discussion HIV E35D;H69K;M36I;R41K;R41K 250;24;256;15;265 254;28;260;19;269 PR 109 117 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. M36I is a common nonsubtype B polymorphism in the absence of drug pressure and also has a higher replication capacity than subtype B wild type virus. 2010 AIDS (London, England) Discussion HIV M36I 0 4 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. Of the polymorphisms identified, I13 V, E35D, M36I, R41K and H69K were associated with known epitopes recognized by HLA class I alleles predominantly found in this population. 2010 AIDS (London, England) Discussion HIV E35D;H69K;I13V;M36I;R41K 40;61;33;46;52 44;65;38;50;56 20009919 Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. Polymorphisms in the protease gene were common with the M36I polymorphism being the most frequent, and it most likely represents the natural genotype of CRF01_AE, whilst the R41K and H69K polymorphisms are more likely attributable to CTL recognition of known epitopes in populations with particular HLA haplotypes. 2010 AIDS (London, England) Discussion HIV H69K;M36I;R41K 183;56;174 187;60;178 PR 21 29 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. In patients with earlier first-line treatment failure and have developed either only M184V or with few TAMs, the option of NRTI backbone is still not limited. 2009 AIDS research and therapy Discussion HIV M184V 85 90 NRTI 123 127 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. Our data indicate that ritonavir-boosted lopinavir monotherapy combined with recycled lamivudine can maintain virological suppression in a substantial proportion of patients who were failing NNRTI-based regimens with M184V, TAMs and NNRTI mutations but were naive to protease inhibitor. 2009 AIDS research and therapy Discussion HIV M184V 217 222 PR;NNRTI;NNRTI 267;191;233 275;196;238 20030841 Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who had NRTI and NNRTI failure. Ritonavir-boosted lopinavir combined with recycled lamivudine to decrease viral fitness can maintain virological suppression in a substantial proportion of patients failing NRTI and NNRTI with M184V and provides adequate plasma concentrations of lopinavir although incidence of low-level viremia is relatively high. 2009 AIDS research and therapy Discussion HIV M184V 193 198 NNRTI;NRTI 182;173 187;177 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. A synergistic impairment (>90% in binding impairment) in the C3d-CR2 interaction was shown by the double C3d mutant (D163A-N170R). 2010 Immunology letters Discussion HIV D163A;N170R 117;123 122;128 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Despite this, the mutation at this residue (R162A) did not improve or impair the affinity of C3d for CR2. 2010 Immunology letters Discussion HIV R162A 44 49 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Furthermore, since the mutations introduced eliminate the overall negative charge (D163A and/or N170R) of C3d, the data also suggest that the interaction with the possible secondary receptor also depends on the electrostatic nature of the molecules. 2010 Immunology letters Discussion HIV D163A;N170R 83;96 89;101 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. However, combining these two mutations (D163A and N170R) almost completely eliminated the elicitation of anti- Envgp120 antibodies, which correlated with the ablation of C3d binding to CR2. 2010 Immunology letters Discussion HIV D163A;N170R 40;50 46;55 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. However, this is very unlikely, since mutations at the neighboring residue (D163A) did have an effect of the binding affinity of Envgp120-C3d2 for CR2. 2010 Immunology letters Discussion HIV D163A 76 81 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. In contrast, mutations at residues D163A and N170R reduced the binding affinity of Envgp120-C3d2 for CR2, by 30% and 70% respectively. 2010 Immunology letters Discussion HIV D163A;N170R 35;45 40;50 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. In the current study, mutations that reduced (D163A or N170R) or eliminated (D163A-N170R) the interaction between C3d and CR2 resulted in reduced or complete elimination of the C3d-induced adjuvant effect. 2010 Immunology letters Discussion HIV D163A;D163A;N170R;N170R 46;77;55;83 52;82;60;88 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. In the current study, previously reported mutations that alter the binding avidity of C3d (R162A, D163A, N170R) for CR2 were engineered. 2010 Immunology letters Discussion HIV D163A;N170R;R162A 98;105;91 103;110;96 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Meanwhile, mutation R170N was tested on for its binding avidity to full-length soluble CR2 on a competition ELISA. 2010 Immunology letters Discussion HIV R170N 20 25 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. Mutations on the interacting surface (N170R) or adjacent areas (D163A) that alter the negatively charged nature of C3d impair the binding of C3d with CR2 and alter the adjuvant potential of C3d. 2010 Immunology letters Discussion HIV D163A;N170R 64;38 69;43 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. The D163A mutation was tested for its binding avidity to the full length CR2 molecule on Raji cells. 2010 Immunology letters Discussion HIV D163A 4 9 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. The mutation that enhanced the binding avidity of C3d (K162A) replaced a basic (positively charged) for a neutral residue. 2010 Immunology letters Discussion HIV K162A 55 60 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. These mutations were selected due to the significantly higher effect on the interaction with CR2 that has been reported and include 1) a mutation that enhanced the binding affinity for CR2 (K162R), 2) a single mutation that significantly impairs the avidity for CR2 and located in the non-interacting surface (>95% impairment) and 3) a mutation that reduced the affinity for CR2 and located on the interacting surface. 2010 Immunology letters Discussion HIV K162R 190 195 20064559 C3d adjuvant activity is reduced by altering residues involved in the electronegative binding of C3d to CR2. This reinforces the hypothesis that residues at the interacting and non-interacting surfaces of C3d are important for binding to CR2 and also confirms the electrostatic nature of the interaction between these proteins, since the mutations removed a negative charge (D163A) and added a positive one (N170R), respectively, therefore increasing the overall positive charge in C3d. 2010 Immunology letters Discussion HIV D163A;N170R 266;299 271;304 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. 1A-D and data not shown), which is in agreement with a recent report that also utilized the S52A variant. 2010 Retrovirology Discussion HIV S52A 92 96 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. In the 293T experiments, S52A showed a similar phenotype like S2/6. 2010 Retrovirology Discussion HIV S52A 25 29 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. In the present study we demonstrate that the S52A mutation in Vpu impairs the ability of HIV-1 to replicate in macrophages, but not in ex vivo infected HLT cultures or PBL. 2010 Retrovirology Discussion HIV S52A 45 49 Vpu 62 65 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. One possible explanation of the remaining anti-tetherin activity of the S52A mutant is that Vpu uses alternative pathways to counteract the restriction factor. 2010 Retrovirology Discussion HIV S52A 72 76 Vpu 92 95 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. This could explain why the S52A Vpu exerts some residual counteracting activity, despite the fact that it does not efficiently induce tetherin degradation. 2010 Retrovirology Discussion HIV S52A 27 31 Vpu 32 35 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. This difference is most likely due to a reduced capability in counteracting tetherin, as the S52A Vpu mutant virus showed a wildtype phenotype in cells that express relatively low levels of this restriction factor. 2010 Retrovirology Discussion HIV S52A 93 97 Vpu 98 101 20078884 Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. While most groups investigated Vpu with mutations in both serines at positions 52 and 56 (S2/6), we utilized the Vpu S52A mutant in our experiments. 2010 Retrovirology Discussion HIV S52A 117 121 Vpu;Vpu 31;113 34;116 20096702 A dynamic model of HIV integrase inhibition and drug resistance. But the two binding modes that raltegravir is predicted to display against the wild type appear to explain why the E92Q/N155H double mutant is highly raltegravir-resistant. 2010 Journal of molecular biology Discussion HIV E92Q;N155H 115;120 119;125 20096702 A dynamic model of HIV integrase inhibition and drug resistance. E92Q is linked with N155H to make a double mutant that is far more raltegravir-resistant than either single mutant. 2010 Journal of molecular biology Discussion HIV N155H;E92Q 20;0 25;4 20096702 A dynamic model of HIV integrase inhibition and drug resistance. If the current preliminary hypothesis of the mechanism of drug resistance for the E92Q/N155H mutant is correct, then a very different strategy should be useful when designing inhibitors with enhanced efficacy against this double mutant. 2010 Journal of molecular biology Discussion HIV E92Q;N155H 82;87 86;92 20096702 A dynamic model of HIV integrase inhibition and drug resistance. In addition, if raltegravir induces any significant structural changes in the catalytic domain to achieve its high affinity and inhibitory activity, then its binding would likely pay a larger enthalpic penalty to induce such changes in this more rigid G140S/Q148H mutant. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 252;258 257;263 20096702 A dynamic model of HIV integrase inhibition and drug resistance. In addition, mutant integrase enzymes with Y143F are competent at replication, and mutants with Y143N are viable but have a delayed replication phenotype. 2010 Journal of molecular biology Discussion HIV Y143F;Y143N 43;96 48;101 IN 20 29 20096702 A dynamic model of HIV integrase inhibition and drug resistance. In an in vitro study using site-directed mutagenesis, Y143F was more than twice as active as the H67F mutant. 2010 Journal of molecular biology Discussion HIV H67F;Y143F 97;54 101;59 20096702 A dynamic model of HIV integrase inhibition and drug resistance. In another study the H67S mutant displayed integrase activity similar to a F185K "wild type model," but this assay was performed with manganese instead of magnesium, which is known to significantly affect the sequence specificity of the interactions between HIV integrase and the viral cDNA, at least. 2010 Journal of molecular biology Discussion HIV F185K;H67S 75;21 80;25 IN;IN 43;262 52;271 20096702 A dynamic model of HIV integrase inhibition and drug resistance. In patients failing therapy with either raltegravir or elvitegravir, the mutations Y143R/C/H have been detected, but no mutations of H67 have been observed in patients. 2010 Journal of molecular biology Discussion HIV Y143C;Y143H;Y143R 83;83;83 92;92;92 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Should this hypothesis of the mechanisms of drug-resistance for the G140S/Q148H mutant be correct, then the following strategy would be useful in guiding the design and evaluation of integrase inhibitors with resistance profiles superior to raltegravir: create fairly rigid compounds with structures that are pre-optimized to interact well with the closed conformations of this double mutant and the wild type integrase. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 68;74 73;79 IN;IN 183;410 192;419 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Since the Y143R/G/F mutants of integrase are viable and infective, and since no mutants of H67 have yet been encountered in patients, the sum of these data suggests that H67 is more likely to play a catalytic role than Y143. 2010 Journal of molecular biology Discussion HIV Y143F;Y143G;Y143R 10;10;10 19;19;19 IN 31 40 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The E92Q/N155H mutant's MD exhibited a higher amplitude and frequency of oscillations between open and closed states. 2010 Journal of molecular biology Discussion HIV E92Q;N155H 4;9 8;14 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The fact that the primary mode interacts well with N155 and displays a better binding energy than the flipped mode is in good agreement with the known trends in resistance profiles for the N155H and E92Q single mutants. 2010 Journal of molecular biology Discussion HIV E92Q;N155H 199;189 203;194 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The G140S/Q148H mutant's ensemble of snapshots was much less accessible to the predicted primary binding mode of raltegravir, and the flipped binding mode was never observed against this mutant. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 4;10 9;15 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The G140S/Q148H mutant's MD showed more restricted motion around a distorted, closed conformation of the 140s loop. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 4;10 9;15 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The primary mode was much less accessible in the G140S/Q148H mutant's ensemble of conformations. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 49;55 54;60 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The single mutation N155H is a primary/signature mutation that confers raltegravir-resistance in the clinic. 2010 Journal of molecular biology Discussion HIV N155H 20 25 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The trend in accessibility indicates that "kinetic gating" could contribute to the drug-resistance profile of the G140S/Q148H mutant. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 114;120 119;125 20096702 A dynamic model of HIV integrase inhibition and drug resistance. The Y143G mutant is also infective, but H67E and H67Q/K71E are not infective, with the latter double mutant being completely defective. 2010 Journal of molecular biology Discussion HIV H67E;H67Q;K71E;Y143G 40;49;54;4 44;53;58;9 20096702 A dynamic model of HIV integrase inhibition and drug resistance. These differences in conformational preferences and dynamic flexibility displayed by the 140s loop, combined with the significant differences in the dynamic display pattern of the critical H67 residue, contribute to the fact that the G140S/Q148H mutant's ensemble contained many fewer conformations against which raltegravir could dock well, relative to the wild type. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 234;240 239;245 20096702 A dynamic model of HIV integrase inhibition and drug resistance. Thus, the results presented indicate that kinetic gating and/or induced fit effects are plausible mechanisms for raltegravir resistance of the G140S/Q148H mutant. 2010 Journal of molecular biology Discussion HIV G140S;Q148H 143;149 148;154 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. A more likely explanation is that Y181C and K103N mutants present at higher levels had already been identified by population sequencing, since samples from those subjects were not retested by ASPCR. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 44;34 49;39 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Alternatively, the low-level EFV resistance conferred by Y181C could have allowed ongoing virus replication that led, in turn, to the later accumulation of other NNRTI resistance mutations such as K103N or G190S. 2010 The Journal of infectious diseases Discussion HIV G190S;K103N;Y181C 206;197;57 211;202;62 NNRTI 162 167 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Although subjects with minority Y181C variants were at greater risk of virologic failure, 70% of these subjects nevertheless achieved long-term viral suppression on their initial efavirenz-based regimen. 2010 The Journal of infectious diseases Discussion HIV Y181C 32 37 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Although the presence of pre-existing low-abundance Y181C mutants was associated with a greater risk of virologic failure, other EFV resistance mutations were more commonly found at the time of virologic failure. 2010 The Journal of infectious diseases Discussion HIV Y181C 52 57 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Because the modified ASPCR method used in the CDC study was designed to detect mutant viruses above the natural quasispecies frequency of each mutation, the actual threshold for detecting the K103N and Y181C mutants was 0.9% and 1.0%, respectively, which is at least two orders of magnitude higher than with our approach. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 192;202 197;207 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Detection of pre-existing minority Y181C mutants encoding NNRTI resistance was associated with a more than 3-fold increased risk of virological failure to initial ART with efavirenz-based regimens in ART-naive HIV-1-infected subjects in the presence of perfect adherence. 2010 The Journal of infectious diseases Discussion HIV Y181C 35 40 NNRTI 58 63 HIV infections 210 224 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. However, this discrepancy may be attributable to the relatively small number of subjects with low-abundance K103N mutants identified by ASPCR. 2010 The Journal of infectious diseases Discussion HIV K103N 108 113 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Importantly, the impact of the presence of low-abundance Y181C mutants on the risk of virologic failure was diminished among non-adherent subjects. 2010 The Journal of infectious diseases Discussion HIV Y181C 57 62 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. In the current study, we did not detect an association with the presence of low-abundance K103N mutants and increased risk of virologic failure. 2010 The Journal of infectious diseases Discussion HIV K103N 90 95 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. It is possible that presence of the Y181C mutants was a marker for presence of other, undetected NNRTI mutants that emerged under efavirenz selection. 2010 The Journal of infectious diseases Discussion HIV Y181C 36 41 NNRTI 97 102 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. M184V) could have influenced the risk of virological failure. 2010 The Journal of infectious diseases Discussion HIV M184V 0 5 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Minority Y181C and K103N mutants were detected by ASPCR in nearly 40% of subjects with wildtype virus by standard genotypic testing. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 19;9 24;14 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Mutations Y181C and K103N were chosen for the ASPCR analysis because they are the most frequent NNRTI resistance mutations found after virological failure to nevirapine and efavirenz. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 20;10 25;15 NNRTI 96 101 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. Persistence of Y181C might have been selected against by the coadministration of zidovudine, since Y181C increases HIV-1 susceptibility to that drug. 2010 The Journal of infectious diseases Discussion HIV Y181C;Y181C 15;99 20;104 20102271 Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. This observation contrasts with previous studies, including our own finding in the same study population of a significantly increased risk of virologic failure when K103N was detected by population sequencing. 2010 The Journal of infectious diseases Discussion HIV K103N 165 170 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. Allele-specific PCR revealed that prior exposure to delavirdine or nevirapine was more strongly associated with the presence of Y181C variants at frequencies >0.5 - 1.0% in entry samples than with K103N variants at similar frequencies. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 197;128 202;133 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. By contrast, K103N at frequencies >0.5 - 1% was strongly associated with decreased virologic response to efavirenz-containing regimens, whereas Y181C variants were not significantly associated with response. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 13;144 18;149 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. In one of 15 NNRTI-naive subjects (7N; figure 2A), an entry sequence containing K103N clustered closely with all the mutant sequences at failure containing K103N with M230L or Y181C. 2010 The Journal of infectious diseases Discussion HIV K103N;K103N;M230L;Y181C 80;156;167;176 85;161;172;181 NNRTI 13 18 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. K103N) can confer high-level cross-resistance to other NNRTI and that such mutations can be detected by several methods, including single-genome sequencing and allele-specific PCR. 2010 The Journal of infectious diseases Discussion HIV K103N 0 5 NNRTI 55 60 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. This difference is likely explained by the preferential selection of Y181C over K103N by nevirapine and to a lesser extent by delavirdine. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 80;69 85;74 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. This evidence includes i) more frequent detection of minor NNRTI-resistant variants in NNRTI-experienced than NNRTI-naive patients by two different methods (single-genome sequencing and allele-specific PCR), ii) strong phylogenetic relatedness in several subjects between single-genome sequences containing NNRTI resistance mutations detected before the initiation of efavirenz-containing therapy and those present at the time of virologic failure, and iii) a significant association between K103N variants at frequencies >0.5-1% and reduced HIV-1 RNA response to efavirenz-containing regimens. 2010 The Journal of infectious diseases Discussion HIV K103N 492 497 NNRTI;NNRTI;NNRTI;NNRTI 59;87;110;307 64;92;115;312 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. This finding is consistent with greater fitness and higher level resistance of K103N variants to efavirenz than Y181C variants. 2010 The Journal of infectious diseases Discussion HIV K103N;Y181C 79;112 84;117 20102272 Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. This observation suggests that the virus population at failure evolved from a K103N mutant population detected at entry. 2010 The Journal of infectious diseases Discussion HIV K103N 78 83 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Addition of T477A into the F440V mutant virus resulted in more normal virion RT p66/p51 content and an increase in virion infectivity. 2010 Retrovirology Discussion HIV F440V;T477A 27;12 32;17 RT 77 79 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. As an example, introduction of T477A in the background of the "lethal" F440W/Y441W mutation resulted in an increase of HIV-1 infectivity from near zero to about 70% of wild-type levels. 2010 Retrovirology Discussion HIV F440W;T477A;Y441W 71;31;77 76;36;82 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. Despite the similarity in the phenotype imparted by the W401A and the p51 RNH cleavage site mutations, we do not think that the latter act by reducing RT dimer formation. 2010 Retrovirology Discussion HIV W401A 56 61 RT 151 153 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. So how can a conservative change such as T477A in the RNH domain of RT possibly alleviate this detrimental phenotype? Proteolytic processing occurs with intermediate forms of RT preceding the final p66/51 heterodimer, and RT structures are available only for the latter. 2010 Retrovirology Discussion HIV T477A 41 46 RT;RT;RT 68;175;222 70;177;224 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The compensatory nature of the T477A second-site mutation highlights the importance of maintaining a proteolytically stable form of RT during virus maturation. 2010 Retrovirology Discussion HIV T477A 31 36 RT 132 134 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The intravirion RT processing defects imparted by the p51 RNH cleavage site mutations are similar to those noted with mutations such as W401A, a mutation which impacts RT dimerization. 2010 Retrovirology Discussion HIV W401A 136 141 RT;RT 16;168 18;170 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The predominant consensus change was the conservative second-site substitution T477A, initially identified in the background of an F440V p51 RNH cleavage site mutant. 2010 Retrovirology Discussion HIV F440V;T477A 131;79 136;84 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. The Thr to Ala change at residue 477 is polymorphic, present in about 4% of HIV-1 sequences, suggesting that it may confer some advantage or at least is benign under normal replication conditions. 2010 Retrovirology Discussion HIV T477A 4 36 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. This is consistent with the lack of phenotypic effect following introduction of T477A into a wild-type RT background. 2010 Retrovirology Discussion HIV T477A 80 85 RT 103 105 20122159 The mutation T477A in HIV-1 reverse transcriptase (RT) restores normal proteolytic processing of RT in virus with Gag-Pol mutated in the p51-RNH cleavage site. We surmise that a T477A substitution would eliminate this hydrogen bond, resulting in increased regional flexibility such that proteolytic cleavage occurs at an alternate site despite the continued presence of the p51 RNH mutations. 2010 Retrovirology Discussion HIV T477A 18 23 20174661 HIV drug resistance surveillance using pooled pyrosequencing. Pyrosequencing reads of both the SDR mutations, M46L and I84V, identified by Sanger sequencing, were found be tightly clustered and almost exclusively associated with the mutant Sanger sequences. 2010 PloS one Discussion HIV I84V;M46L 57;48 61;52 20174661 HIV drug resistance surveillance using pooled pyrosequencing. The dendograms for the M46L and I84V mutations detected by pyrosequencing were unique among those SDRM found at frequencies of less than 1%. 2010 PloS one Discussion HIV I84V;M46L 32;23 36;27 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In general, emergent resistance to K65R is rare. 2009 HIV therapy Discussion HIV K65R 35 39 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. In summary, the rarity of K65R development with TDF-based regimens has enormous clinical potential towards the development of cost-effective HIV therapeutic and prevention strategies. 2009 HIV therapy Discussion HIV K65R 26 30 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The bidirectional antagonism between K65R and TAM pathways hold the promise of developing NRTI resistance-sparing regimens that combine AZT/TDF/ABC with FTC or 3TC. 2009 HIV therapy Discussion HIV K65R 37 41 NRTI 90 94 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The combined dangers of TAM and K65R resistance, facilitated by synergistic NVP resistance (Y181C/G190A), may lead to situations where the choice of second-line regimens is limited. 2009 HIV therapy Discussion HIV G190A;K65R;Y181C 98;32;92 103;36;97 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The facilitated development of K65R, M184V and/or L74V as a minority species leads to early treatment failure with suboptimal treatment regimens, in particular d4T, ddI, NVP and triple-NRTI drug combinations. 2009 HIV therapy Discussion HIV K65R;L74V;M184V 31;50;37 35;54;42 NRTI 185 189 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The high barrier to K65R development and the benefit of K65R and M184V in viral suppression, have led to the hope that TDF and TDF/FTC regimens may be used in microbicide- and chemoprophylaxis-prevention strategies. 2009 HIV therapy Discussion HIV K65R;K65R;M184V 20;56;65 24;60;70 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The K65R mutation results in diminutions in viral replicative capacity similar to that observed for the M184V mutation. 2009 HIV therapy Discussion HIV K65R;M184V 4;104 8;109 20190870 The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. The recent report of transmitted K65R resistance in four out of four breast-feeding infants from mothers harboring K65R illustrates the potential public health concern of transmitted drug resistance. 2009 HIV therapy Discussion HIV K65R;K65R 33;115 37;119 20227665 Flexible use of nuclear import pathways by HIV-1. A more distantly related lentivirus, FIV, behaved remarkably similar to N74D HIV-1 in infection assays. 2010 Cell host & microbe Discussion HIV N74D 72 76 20227665 Flexible use of nuclear import pathways by HIV-1. Because N74D mutation of HIV-1 CA enhanced rhTRIM5alpha binding, it is conceivable that TRIM5alpha in vivo additionally counterselects an N74D core in primate lentiviruses. 2010 Cell host & microbe Discussion HIV N74D;N74D 8;138 12;142 Capsid 31 33 20227665 Flexible use of nuclear import pathways by HIV-1. By contrast, E45A or Q63A/Q67A HIV-1 are impaired in the infection of nondividing cells and potently restricted when these cells express mCPSF6-358. 2010 Cell host & microbe Discussion HIV E45A;Q63A;Q67A 13;21;26 17;25;30 20227665 Flexible use of nuclear import pathways by HIV-1. Dependence on NUP155 expression correlated with resistance to mCPSF6-358, raising the possibility that this factor directly interacts with N74D HIV-1 or FIV PICs. 2010 Cell host & microbe Discussion HIV N74D 139 143 20227665 Flexible use of nuclear import pathways by HIV-1. Experiments with N74D HIV-1 indicate that TNPO3 is not required for nuclear entry. 2010 Cell host & microbe Discussion HIV N74D 17 21 20227665 Flexible use of nuclear import pathways by HIV-1. In contrast, infection by the N74D mutant was less dependent on TNPO3, RANBP2, or NUP153, suggesting that these proteins interacted, directly or indirectly, with wild-type CA during infection. 2010 Cell host & microbe Discussion HIV N74D 30 34 Capsid 172 174 20227665 Flexible use of nuclear import pathways by HIV-1. N74D CA has so far been observed in one primate lentiviral isolate, SIVcpz MT145, but is otherwise rare in known HIV-1/HIV-2/SIV isolates. 2010 Cell host & microbe Discussion HIV N74D 0 4 Capsid 5 7 20227665 Flexible use of nuclear import pathways by HIV-1. Nonetheless, in dividing cells E45A and Q63A/Q67A HIV-1 were generally less affected by depletion of TNPO3 or NUPs relative to wild-type and N74D HIV-1, albeit they were not as insensitive as MLV (data not shown). 2010 Cell host & microbe Discussion HIV E45A;N74D;Q63A;Q67A 31;141;40;45 35;145;44;49 20227665 Flexible use of nuclear import pathways by HIV-1. NUP85 knockdowns also appeared to diminish N74D HIV-1 infection but to a lesser extent, whereas wild-type HIV-1 and the N74D mutant shared infection sensitivity to NUP160 depletion. 2010 Cell host & microbe Discussion HIV N74D;N74D 43;120 47;124 20227665 Flexible use of nuclear import pathways by HIV-1. The combined effect of cellular growth arrest and siRNA depletion of NUPs on E45A and Q63A/Q67A HIV-1 infection could not be evaluated due to cytotoxicity. 2010 Cell host & microbe Discussion HIV E45A;Q63A;Q67A 77;86;91 81;90;95 20227665 Flexible use of nuclear import pathways by HIV-1. The enhanced restriction of wild-type but not N74D HIV-1 by CPSF6-358 in nondividing cells prompted further examination of the transport and NUPs recently identified as potential HIV-1 co-factors in siRNA screens. 2010 Cell host & microbe Discussion HIV N74D 46 50 20227665 Flexible use of nuclear import pathways by HIV-1. The N74D mutant had an increased dependency on NUP155. 2010 Cell host & microbe Discussion HIV N74D 4 8 20227665 Flexible use of nuclear import pathways by HIV-1. These data indicate that N74D HIV-1 and FIV use similar strategies to access the nucleus and that avoiding interaction with CPSF6-358 profoundly alters the nuclear entry pathway (Figure 7B). 2010 Cell host & microbe Discussion HIV N74D 25 29 20227665 Flexible use of nuclear import pathways by HIV-1. Underscoring the pivotal role of HIV-1 CA in cytoplasmic-nuclear trafficking, other CA mutations, E45A and Q63A/Q67A, enable mCPSF6-358 evasion by HIV-1, but only in dividing cells. 2010 Cell host & microbe Discussion HIV E45A;Q63A;Q67A 98;107;112 102;111;116 Capsid;Capsid 39;84 41;86 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Extensive structural and biochemical analyses on the wild type and H69D precursor would be essential to provide insights into protease autoprocessing mechanisms. 2010 Retrovirology Discussion HIV H69D 67 71 PR 126 134 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. However, in the context of H69E pseudo wild type protease, cysteine containing protease demonstrated a relative Gag processing activity higher than that lacking cysteines (Figure 2A). 2010 Retrovirology Discussion HIV H69E 27 31 PR;PR;Gag 49;79;112 57;87;115 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Previous biochemical analyses demonstrated that H69E mutation significantly delays the TFR-PR precursor from autoprocessing in vitro; whereas the appropriately folded H69E mature protease only showed a slightly decreased catalytic activity. 2010 Retrovirology Discussion HIV H69E;H69E 48;167 52;171 PR;PR 179;91 187;93 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. The current study demonstrates that L63, C67, and C95 dampen the H69E inhibitory effect. 2010 Retrovirology Discussion HIV H69E 65 69 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. This cysteine modification cycle seems unnecessary for protease autoprocessing and mature protease activity as the pseudo wild type protease containing mutations C67A/C95A is able to process Gag polyprotein at levels comparable, yet slightly lower, to NL4-3 protease (Figure 2 and 3). 2010 Retrovirology Discussion HIV C67A;C95A 162;167 166;171 PR;PR;PR;PR;Gag 55;90;132;258;191 63;98;140;266;194 20331855 Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. We previously reported that H69E mutation in a pseudo wild type protease sequence abolishes protease autoprocessing in E. 2010 Retrovirology Discussion HIV H69E 28 32 PR;PR 64;92 72;100 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Because the IN mutants H171A, L172A and EH170,1AA bound to chromatin but not LEDGF/p75, we further reconfirmed the LEDGF/p75 independent chromatin binding of wild type IN using the LEDGF/p75-KD cells. 2010 Virology journal Discussion HIV H171A;L172A 23;30 28;35 IN;IN 12;168 14;170 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. However, given the fact that both A179P and A179I lost binding to host chromatin, the A179 residue may be directly involved in interacting with host chromatin. 2010 Virology journal Discussion HIV A179I;A179P 44;34 49;39 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. In this study, we identified another mutant F185A that displayed a significant reduction in the interaction with LEDGF and chromatin, but to a lesser extent than that of KR186,7AA. 2010 Virology journal Discussion HIV F185A 44 49 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Indeed, this could be the case for the IN mutant I203P because another mutant I203A was able to efficiently bind host DNA and LEDGF/p75. 2010 Virology journal Discussion HIV I203A;I203P 78;49 83;54 IN 39 41 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Interestingly, in our study, IN mutants K159A, V165A, V176A, A179P, KR186,7AA are located within this region and were identified as chromatin-binding defective mutants. 2010 Virology journal Discussion HIV A179P;K159A;V165A;V176A 61;40;47;54 66;45;52;59 IN 29 31 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Interestingly, two IN mutants, H171A and L172A within the CCD of IN, displayed a different phenotype; they could not efficiently interact with LEDGF/p75 yet still could bind chromatin. 2010 Virology journal Discussion HIV H171A;L172A 31;41 36;46 IN;IN 19;65 21;67 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Nevertheless, the chromatin-binding phenotype of K159P, A179P and I203P IN mutants suggest the involvement of alpha-helices 4, 5 and 6 of IN in host DNA recognition. 2010 Virology journal Discussion HIV A179P;I203P;K159P 56;66;49 61;71;54 IN;IN 72;138 74;140 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Our previous results showed that chromatin binding defective IN mutants (V165A, A179P, KR186,7AA) also fail to interact with LEDGF/p75, suggesting that LEDGF-binding of IN might be linked to the chromatin-binding affinity of IN. 2010 Virology journal Discussion HIV A179P;V165A 80;73 85;78 IN;IN;IN 61;169;225 63;171;227 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Results showed that several IN mutants including K159P, V165A, V176A, A179P, KR186,7AA and I203P were unable to bind both LEDGF/p75 and host chromatin. 2010 Virology journal Discussion HIV A179P;I203P;K159P;V165A;V176A 70;91;49;56;63 75;96;54;61;68 IN 28 30 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. The mutants H171A, L172A and EH170,1AA, located in a loop region 170EHLK173 of IN, severely impaired their interaction with LEDGF/p75 but were still able to bind chromatin. 2010 Virology journal Discussion HIV H171A;L172A 12;19 17;24 IN 79 81 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. The results showed that IN mutants K159P, A179P and I203P located at the alpha-helices 4, 5 and 6 specifically affected both chromatin- and LEDGF/p75-binding abilities. 2010 Virology journal Discussion HIV A179P;I203P;K159P 42;52;35 47;57;40 IN 24 26 20331877 Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase. Two other IN mutants that need to be addressed are KR186,7AA and F185A. 2010 Virology journal Discussion HIV F185A 65 70 IN 10 12 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. However, the dominant W680G variant in this subject almost completely disappeared three years later, suggesting that whatever pressure selected for this variant was transitory in nature. 2010 PloS one Discussion HIV W680G 22 27 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. In a recent study of in vitro generated MPER mutants, a W680G substitution was found to have the smallest negative impact on Env fusogenicity. 2010 PloS one Discussion HIV W680G 56 61 Env 125 128 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. In fact, our substitution of a W680G containing cassette (KGQI) into an unrelated subtype C reference env produced neutralization data similar to that reported with the substitution of another small hydrophobic residue (A) for the tryptophan at position 680. 2010 PloS one Discussion HIV W680G 31 36 Env 102 105 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Many of our gp41s have an exceedingly rare neutral substitution (K683Q), tied to the identity of residue 680. 2010 PloS one Discussion HIV K683Q 65 70 gp41 12 17 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. Of the seven major MPER sequence variants we identified in subject-pairs 12 and 16, four of them had substitutions at position 683 that eliminated the CRAC motif (K683Q), yet were functional and represented significant portions of those subject's quasi-species. 2010 PloS one Discussion HIV K683Q 163 168 20352106 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. This is one possible explanation for why the W680G mutation was favored in subject 16M at the early time point and why it was transmitted. 2010 PloS one Discussion HIV W680G 45 50 20377404 Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure. Specifically, women with a proviral population containing greater than 5% resistant mutants (K103N, Y181C or G190A) were significantly more likely to experience virologic failure. 2010 Clinical infectious diseases Discussion HIV G190A;K103N;Y181C 109;93;100 114;98;105 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Another important finding of these studies is that the NNRTI-resistance mutations K101E and G190S interact to affect a variety of phenotypes, leading to increased EFV resistance, reduced replication fitness in the absence of drug, and EFV-dependent stimulation of virus replication. 2010 Virology Discussion HIV G190S;K101E 92;82 97;87 NNRTI 55 60 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. It is unclear at present how both L74V and TAMs might reduce or eliminate EFV-dependent stimulation; this effect appears independent of the effects of these nucleoside resistance mutations on EFV IC50. 2010 Virology Discussion HIV L74V 34 38 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. L74V, in addition to improving the fitness of G190E and K103N+L100I, also has the same effect on (K101E+G190S). 2010 Virology Discussion HIV G190E;G190S;K101E;K103N;L100I;L74V 46;104;98;56;62;0 51;109;103;61;67;4 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Our preliminary evidence shows that dimerization of K101E+G190S is not stimulated by EFV. 2010 Virology Discussion HIV G190S;K101E 58;52 63;57 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Our study, however, is the first demonstration that thymidine analog mutations (TAMs), such as M41L+T215Y, can also augment the replication fitness of an NNRTI-resistant mutant. 2010 Virology Discussion HIV M41L;T215Y 95;100 99;105 NNRTI 154 159 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Studies in which resistance mutations in the D10 backbone were reverted to wild type indicate that some RT polymorphisms can augment the impact of K101E+G190S on EFV-dependent stimulation of replication and reduce the ability of M41L+T215Y to reverse the drug-dependent stimulation conferred by K101E+G190S. 2010 Virology Discussion HIV G190S;G190S;K101E;K101E;M41L;T215Y 153;301;147;295;229;234 158;306;152;300;233;239 RT 104 106 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The modulating effects of RT polymorphisms in the D10 RT backbone are dependent on the presence of K101E (and also presumably G190S, although this was not directly tested in our studies). 2010 Virology Discussion HIV G190S;K101E 126;99 131;104 RT;RT 26;54 28;56 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. The TAM double mutant (M41L+T215Y) also abolishes EFV-dependent stimulation of growth, similar to L74V, but unlike L74V, sensitizes the virus to EFV. 2010 Virology Discussion HIV L74V;L74V;M41L;T215Y 98;115;23;28 102;119;27;33 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. They also showed that the fitness of very poorly replicating mutants was better in the patient backbone where the mutation occurred and that L74V enhanced the replication of G190S and other mutants which is consistent with our results. 2010 Virology Discussion HIV G190S;L74V 174;141 179;145 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. This finding is compatible with previously published studies of L74V and NNRTI-resistant variants. 2010 Virology Discussion HIV L74V 64 68 NNRTI 73 78 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Thus, it is possible that the K101E mutation in combination with G190S leads to destabilization of the reverse transcriptase heterodimer that is partially compensated for by weak binding of EFV, resulting in EFV-dependent stimulation of HIV-1 reverse transcription. 2010 Virology Discussion HIV G190S;K101E 65;30 70;35 RT;RT 243;103 264;124 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Using this factor adjusts mean Cmin and Cmax values of 5.6 muM and 12.9 muM observed in patients (quoted in the efavirenz package insert) to give corresponding tissue culture values of 339 nM and 781 nM, respectively, which are in the range of the efavirenz concentrations at which we observed stimulation of the K101E+G190S mutants. 2010 Virology Discussion HIV G190S;K101E 319;313 324;318 20399480 The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. We have observed this phenomenon with the (K101E+G190S) mutant, and have confirmed the initial report that M230L has this property (Huang W., Parkin N.T., Lie, Y.S., et al. 2010 Virology Discussion HIV G190S;K101E;M230L 49;43;107 54;48;112 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Despite impairment of IN activities observed in vitro, Y143C and Y143R mutants viruses are able to replicate efficiently in vivo. 2010 PloS one Discussion HIV Y143C;Y143R 55;65 60;70 IN 22 24 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Experiments performed with integrase carrying the Y143C mutation showed that it retains single-end strand transfer activity and can crosslink with blunt-end DNA, suggesting that the contact is maintained with the viral DNA during the conformational change between the 3'processing and strand transfer step. 2010 PloS one Discussion HIV Y143C 50 55 IN 27 36 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Further experiments should focus on the role of T97A by introducing this mutation alone into the integrase gene. 2010 PloS one Discussion HIV T97A 48 52 IN 97 106 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Further research is warranted to investigate whether the impact of Y143C/R on IN functions and on resistance to RAL at the enzymatic level could be modulated by secondary INI resistance mutations. 2010 PloS one Discussion HIV Y143C;Y143R 67;67 74;74 IN;IN 171;78 174;80 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. How could the selected mutations impair RAL binding while allowing alternative DNA recognition? We observed (data not shown) a lower binding to DNA substrate in the case of mutant Y143R. 2010 PloS one Discussion HIV Y143R 180 185 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In all the patients, Y143R/C with secondary mutations replaced the N155H mutation. 2010 PloS one Discussion HIV N155H;Y143C;Y143R 67;21;21 72;28;28 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In conclusion, we characterized the selection dynamics of the IN mutations Y143R/C in patients failing on RAL-containing regimens. 2010 PloS one Discussion HIV Y143C;Y143R 75;75 82;82 IN 62 64 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In the three patients studied here, the M154L and V165I mutations, which had been associated with previous antiretroviral experience, were not present at baseline. 2010 PloS one Discussion HIV M154L;V165I 40;50 45;55 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. In this work, we further investigate the genetic pathways and the dynamics of emergence of the Y143C/R mutations in the HIV-1 integrase gene in three patients failing on RAL-containing regimens, as well as the influence of Y143C/R mutations on IN functions and on the sensitivity of IN to RAL. 2010 PloS one Discussion HIV Y143C;Y143C;Y143R;Y143R 95;223;95;223 102;230;102;230 IN;IN;IN 126;244;283 135;246;285 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Interestingly, in all three patients, the N155H mutation appeared at M1 or M3, and then disappeared with a switch to the emergence of the Y143C/H/R mutation detected 3 months later. 2010 PloS one Discussion HIV N155H;Y143C;Y143H;Y143R 42;138;138;138 47;147;147;147 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Moreover, our cloning analysis showed that some clones could carry T97A in the absence of Y143C/R and other major mutations, suggesting that T97A could be sufficient to code resistance to RAL. 2010 PloS one Discussion HIV T97A;T97A;Y143C;Y143R 67;141;90;90 71;145;97;97 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Moreover, the association of mutations T97 and Y143 might increase the resistance level to RAL and/or rescue the catalytic defect due to the Y143C/R mutation. 2010 PloS one Discussion HIV Y143C;Y143R 141;141 148;148 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Of note, the other major mutation Q148R was transiently detected in one patient in one clone at baseline RAL and at month 6, but did not seem to confer any selective advantage over the other mutants in this patient. 2010 PloS one Discussion HIV Q148R 34 39 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. On the other hand, we observed a low binding to DNA substrate in the case of the Y143R mutant which could be responsible for the catalytic defect in this enzyme. 2010 PloS one Discussion HIV Y143R 81 86 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Recent data from site-directed mutants showed a high impact of Y143R on replicative capacity and on phenotypic resistance to RAL (Fransen et al, unpublished data). 2010 PloS one Discussion HIV Y143R 63 68 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Replacement over time of the N155H pattern by the Y143R/C pattern was confirmed by a clonal analysis of the evolution of HIV-1 IN in the three patients, while the Y143H mutation was not confirmed at the clonal level, suggesting that it could be an artifact of the population sequence translation. 2010 PloS one Discussion HIV N155H;Y143C;Y143H;Y143R 29;50;163;50 34;57;168;57 IN 127 129 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Selection of the Y143R/C mutation was accompanied in all three patients by the T97A mutation. 2010 PloS one Discussion HIV T97A;Y143C;Y143R 79;17;17 83;24;24 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Surprisingly, in a recent study on site-directed mutants, the double mutant Y143R + N155H exhibited a selective advantage over other mutants in the presence of RAL. 2010 PloS one Discussion HIV N155H;Y143R 84;76 89;81 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The processing activities of mutants Y143C and Y143R were moderately decreased compared to the wild-type enzyme and the mutations more strongly affected the strand transfer activities of both mutants enzymes when using pre-cleaved substrate. 2010 PloS one Discussion HIV Y143C;Y143R 37;47 42;52 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The switch to Y143R/C was clearly associated with a loss of sensitivity to RAL, with fold-changes of 5.87, 28.52 and 51.95 in patients 1, 2 and 3, respectively. 2010 PloS one Discussion HIV Y143C;Y143R 14;14 21;21 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The T206S polymorphism, which was found to be associated with a worse virological response in our original prospective cohort, was also absent at baseline. 2010 PloS one Discussion HIV T206S 4 9 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. The Y143C/H/R mutation was associated with T97A in 3 patients, with L74M in 2 patients and with G163R and S230R in one patient each. 2010 PloS one Discussion HIV G163R;L74M;S230R;T97A;Y143C;Y143H;Y143R 96;68;106;43;4;4;4 101;72;111;47;13;13;13 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. This co-selection of secondary mutations, particularly T97A, along with the mutations at position 143 are in agreement with other studies. 2010 PloS one Discussion HIV T97A 55 59 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. This could explain the high difference of FC to RAL found between in vitro mutant IN with Y143C/R alone, or ex vivo with recombinant viruses from patients. 2010 PloS one Discussion HIV Y143C;Y143R 90;90 97;97 IN 82 84 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. This mutation seems to enhance the resistance to RAL in the presence of Y143C, as suggested by in vitro experiments on site-directed mutants (Fransen et al, unpublished data). 2010 PloS one Discussion HIV Y143C 72 77 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. This observation is consistent with our finding that the Y143C mutant binds strand transfer substrate. 2010 PloS one Discussion HIV Y143C 57 62 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Thus, further research will be needed to specify the determinants of selection of Y143R/C. 2010 PloS one Discussion HIV Y143C;Y143R 82;82 89;89 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. To observe the effect of mutations Y143C and Y143R on IN activity and RAL sensitivity, the mutated integrases were produced, purified and in vitro 3'end processing, strand transfer and concerted integration were assayed according to standard procedures previously used in our laboratory. 2010 PloS one Discussion HIV Y143C;Y143R 35;45 40;50 IN;IN 99;54 109;56 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. We set up a prospective study including antiretroviral-experienced patients receiving RAL and an optimized background therapy and found a particular pattern of mutations involving IN mutations Y143C/H/R in patients with virological failure with RAL. 2010 PloS one Discussion HIV Y143C;Y143H;Y143R 193;193;193 202;202;202 IN 180 182 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. When the viruses of these three patients replicated on therapy, selection of the mutations L74M, T97A, Y143C/H/R, N155H, G163R and V201I/L was observed in the population sequences originating from plasma HIV-1 RNA. 2010 PloS one Discussion HIV G163R;L74M;N155H;T97A;V201I;V201L;Y143C;Y143H;Y143R 121;91;114;97;131;131;103;103;103 126;95;119;101;138;138;112;112;112 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Y143C/R and N155H seemed to be exclusive in vivo. 2010 PloS one Discussion HIV N155H;Y143C;Y143R 12;0;0 17;7;7 20436677 The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions. Y143R/C mutations conferred a high resistance to RAL in vitro and in vivo. 2010 PloS one Discussion HIV Y143C;Y143R 0;0 7;7 20453629 Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa. Interestingly, among patients failing second-line ART, most were found to harbour DR mutations associated with failure of line-one regimens (particularly the NNRTI mutation, K103N), and there was an extraordinary paucity of PI related mutations. 2010 AIDS (London, England) Discussion HIV K103N 174 179 NNRTI;PI 158;224 163;226 20453629 Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa. Thus, M184V/I, K103N and V106A/M were the most common mutations due to lamivudine and NNRTI use. 2010 AIDS (London, England) Discussion HIV K103N;M184I;M184V;V106A;V106M 15;6;6;25;25 20;13;13;32;32 NNRTI 86 91 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. According to published phenotypic data, only 1 of the 20 triplets is predicted to have high-level resistance to etravirine:K101E, Y181C and G190S:but intermediate resistance to etravirine has previously been associated with the presence of Y181C or K101E plus at least two other NNRTI resistance mutations. 2010 The Journal of antimicrobial chemotherapy Discussion HIV G190S;K101E;K101E;Y181C;Y181C 140;123;249;130;240 145;128;254;135;245 NNRTI 279 284 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Although V179F and G190S do not reduce etravirine susceptibility when they occur individually, they are highly synergistic with Y181C; Y181C + V179F reduces etravirine susceptibility >100-fold and Y181C + G190S reduces etravirine susceptibility ~20-fold. 2010 The Journal of antimicrobial chemotherapy Discussion HIV G190S;G190S;V179F;V179F;Y181C;Y181C;Y181C 19;205;9;143;128;135;197 24;210;14;148;133;140;202 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Although we found that four of the pairs described by these studies consist of mutations selected preferentially by nevirapine (K101E, Y181C, G190A and H221Y) and that K103N and its associated mutations are all selected preferentially by efavirenz, we also found that the covariance of every pair was independent of the particular NNRTI received, suggesting a potential biophysical interaction rather than treatment pressure. 2010 The Journal of antimicrobial chemotherapy Discussion HIV G190A;H221Y;K101E;K103N;Y181C 142;152;128;168;135 147;157;133;173;140 NNRTI 331 336 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Conversely, although the two efavirenz-selected mutations L100I and K101P are major etravirine RAMs, combined they occur in <20% of patients receiving efavirenz. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K101P;L100I 68;58 73;63 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. For example, nevirapine selects for V106A, Y181C/I/V and G190A significantly more frequently than efavirenz, whereas efavirenz preferentially selects for L100I, K101P, V106M, Y188L, G190S and P225H. 2010 The Journal of antimicrobial chemotherapy Discussion HIV G190A;G190S;K101P;L100I;P225H;V106A;V106M;Y181C;Y181I;Y181V;Y188L 57;182;161;154;192;36;168;43;43;43;175 62;187;166;159;197;41;173;52;52;52;180 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. found 11 significant pairwise correlations between NNRTI-selected mutations (P < 0.05 corrected), of which two pairs, K103N/Y181C and K103N/V108I, were not positively correlated in our analysis. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K103N;K103N;V108I;Y181C 118;134;140;124 123;139;145;129 NNRTI 51 56 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. However, most patterns contained one or more minor etravirine RAMs in combination with a major etravirine RAM, particularly Y181C. 2010 The Journal of antimicrobial chemotherapy Discussion HIV Y181C 124 129 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Most of these patterns consisted solely of mutations that covaried with one another (mutational clusters), and the remainder consisted of K103N in combination with one or more pairs of covarying mutations. 2010 The Journal of antimicrobial chemotherapy Discussion HIV K103N 138 143 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Nevirapine-associated etravirine RAMs, including Y181C, G190A and E138A, were also among the most commonly observed mutations in sequences from 782 women treated with a single dose of nevirapine. 2010 The Journal of antimicrobial chemotherapy Discussion HIV E138A;G190A;Y181C 66;56;49 71;61;54 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Nine of these 22 pairs contained major etravirine RAMs: Y181C (n = 7), L100I (n = 1) or K101P (n = 1), but only 2 pairs are predicted to confer moderate to high-level etravirine resistance: Y181C + V179F and Y181C + G190S. 2010 The Journal of antimicrobial chemotherapy Discussion HIV G190S;K101P;L100I;V179F;Y181C;Y181C;Y181C 216;88;71;198;56;190;208 221;93;76;203;61;195;213 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. reported five significant associations among the NNRTI-selected mutations that we studied: Y181C/H221Y, V108I/H221Y, L100I/K103N, K103N/P225H and K103N/K238T. 2010 The Journal of antimicrobial chemotherapy Discussion HIV H221Y;H221Y;K103N;K103N;K103N;K238T;L100I;P225H;V108I;Y181C 97;110;123;130;146;152;117;136;104;91 102;115;128;135;151;157;122;141;109;96 NNRTI 49 54 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The following nine pairs were still significantly correlated in our analysis: Y181C/G190A, K101E/G190A, Y181C/H221Y, V108I/H221Y, L100I/K103N, V108I/Y181C, V106A/F227L, K101E/Y181C and K103N/P225H. 2010 The Journal of antimicrobial chemotherapy Discussion HIV F227L;G190A;G190A;H221Y;H221Y;K101E;K101E;K103N;K103N;L100I;P225H;V106A;V108I;V108I;Y181C;Y181C;Y181C;Y181C 162;84;97;110;123;91;169;136;185;130;191;156;117;143;78;104;149;175 167;89;102;115;128;96;174;141;190;135;196;161;122;148;83;109;154;180 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. These data suggest that patients developing virological failure while receiving nevirapine may be at increased risk of developing virological failure with etravirine because Y181C/I/V:which occurs in 45% of individuals receiving nevirapine:forms the foundation for high-level etravirine resistance. 2010 The Journal of antimicrobial chemotherapy Discussion HIV Y181C;Y181I;Y181V 174;174;174 183;183;183 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. This is because Y181C/I/V occur more commonly with nevirapine than with efavirenz, and because mutations at this position provide the foundation for high-level etravirine resistance. 2010 The Journal of antimicrobial chemotherapy Discussion HIV Y181C;Y181I;Y181V 16;16;16 25;25;25 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. With the exception of the uncommon mutations Y181I/V, multiple mutations are required for moderate to high-level etravirine resistance (>10-fold reduction in susceptibility). 2010 The Journal of antimicrobial chemotherapy Discussion HIV Y181I;Y181V 45;45 52;52 20462946 Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Y181C was the only major etravirine RAM among the 20 most common mutational triplets. 2010 The Journal of antimicrobial chemotherapy Discussion HIV Y181C 0 5 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Although, it should be noted that we could not rule out subtle differences in replication kinetics between the wildtype and I309L mutants that might have been evident in a more sensitive growth competition assay. 2010 Virology Discussion HIV I309L 124 129 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Based on these previous observations, and our current experimental results, we propose that the I309L substitution perturbs the hydrophobic cluster and, by altering the position of the V3 loop, impacts the CD4bs. 2010 Virology Discussion HIV I309L 96 101 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Indeed, a majority of the I309L mutant Envs more efficiently infected a cell line expressing a low level of CD4, focusing the effects of the mutation on utilization of CD4. 2010 Virology Discussion HIV I309L 26 31 Env 39 43 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. It is important to note that we were unable to detect an increase in sensitivity to autologous patient plasma with I309L (data not shown). 2010 Virology Discussion HIV I309L 115 120 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. It is plausible that I309L Envs could be more susceptible to these types of antibodies in vivo, and would therefore be selected against by immune pressure. 2010 Virology Discussion HIV I309L 21 26 Env 27 31 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Replication and spread in two primary target cells, CD4 T cells and MDM, was not overtly reduced by the I309L substitution. 2010 Virology Discussion HIV I309L 104 109 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. sCD4 sensitivity was used in this study as a surrogate for exposure of the CD4bs, and all but two Envs (both from subject 185F) became more sensitive to sCD4 when I309L was introduced. 2010 Virology Discussion HIV I309L 163 168 Env 98 102 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. Since the number and potency of monoclonal antibodies available to probe differences between wildtype and I309L Envs was limited, the effect of I309L on neutralization sensitivity could be underestimated. 2010 Virology Discussion HIV I309L;I309L 106;144 111;149 Env 112 116 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. The moderate enhancement of replication in MDM when I309L was present suggests that this mutation could have altered the viral interaction with CD4. 2010 Virology Discussion HIV I309L 52 57 20494390 Subtype-specific conservation of isoleucine 309 in the envelope V3 domain is linked to immune evasion in subtype C HIV-1 infection. This theory provides a biologically plausible explanation for the I309L CD4 enhanced phenotype described here, as well as a compelling reason for the unique conservation pattern of specific residues within the subtype C V3 domain that may not be critical for viral entry functions. 2010 Virology Discussion HIV I309L 66 71 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. A negative drug-drug interaction between TNV and other NRTIs has also been proposed as an escape mechanism of M184V/I single-mutants from TNV suppression. 2010 Antiviral therapy Discussion HIV M184I;M184V 110;110 117;117 NRTI 55 60 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. By week 12, double-mutants containing K65R and M184V/I were predominant in all five subjects. 2010 Antiviral therapy Discussion HIV K65R;M184I;M184V 38;47;47 42;54;54 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Escape of M184I/V single-mutants remains unexplained because these viruses were fully susceptible or hypersusceptible to TNV. 2010 Antiviral therapy Discussion HIV M184I;M184V 10;10 17;17 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Frequent linkage of K65R and M184V suggests an advantage for double-mutants. 2010 Antiviral therapy Discussion HIV K65R;M184V 20;29 24;34 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Furthermore, 10/20 patients had only M184V detected by standard genotype, indicating that double-mutants were infrequent or not present. 2010 Antiviral therapy Discussion HIV M184V 37 42 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. In summary, the poor virologic response and rapid viral rebound observed with once-daily TNV/ddI/3TC is explained in some patients by resistance to each component of the regimen resulting from two, linked, single nucleotide mutations in reverse transcriptase (K65R and M184V). 2010 Antiviral therapy Discussion HIV K65R;M184V 260;269 265;274 RT 237 258 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Indeed, the population phenotype of samples with "pure" K65R and M184V by standard genotype was more similar to that of individual double-mutant clones, compared to the phenotype of samples with mutant/wild-type "mixtures", which were more like single M184V clones. 2010 Antiviral therapy Discussion HIV K65R;M184V;M184V 56;65;252 60;70;257 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. It may be that TNV doesn't penetrate or isn't phosphorylated to its active metabolite in certain target cells, allowing the M184V single-mutant to replicate. 2010 Antiviral therapy Discussion HIV M184V 124 129 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. K65R and M184V were linked on the same genome in 8/9 patients with both mutants detected by standard genotype, and double-mutants comprised 50% of all sequences. 2010 Antiviral therapy Discussion HIV M184V;K65R 9;0 14;4 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Linkage analysis showed K65R and M184V/I single-mutants were more prevalent at week 4 than at week 12. 2010 Antiviral therapy Discussion HIV K65R;M184I;M184V 24;33;33 28;40;40 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. M184V/I single-mutants comprised 48% of all sequences, whereas only two sequences (1%) were K65R single-mutants. 2010 Antiviral therapy Discussion HIV K65R;M184I;M184V 92;0;0 96;7;7 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Not all of the single genome sequences contained K65R. 2010 Antiviral therapy Discussion HIV K65R 49 53 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Phenotypic analysis of twelve recombinant clones showed a significant decrease in ddI, TNV, and ABC susceptibility for K65R/M184V double-mutants compared to M184V single-mutants (p<0.001). 2010 Antiviral therapy Discussion HIV K65R;M184V;M184V 119;124;157 123;129;162 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. Population phenotype analyses failed to accurately measure combined phenotypic effects of K65R and M184V. 2010 Antiviral therapy Discussion HIV K65R;M184V 90;99 94;104 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. The observed reversal of TNV hypersusceptibility and increased ddI and ABC resistance with the addition of K65R to M184V is consistent with site-directed mutant studies. 2010 Antiviral therapy Discussion HIV K65R;M184V 107;115 111;120 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. The substantially better virologic response of AZT-containing triple NRTI regimens may be due to phenotypic antagonism between the common resistance pathways for AZT (thymidine analog mutations) versus TNV, 3TC, ABC, and ddI (K65R and M184V). 2010 Antiviral therapy Discussion HIV K65R;M184V 226;235 231;240 NRTI 69 73 20516563 Clonal resistance analyses of HIV type-1 after failure of therapy with didanosine, lamivudine and tenofovir. This possibility is supported by the absence of K65R at virologic failure in A5095 and TARGET compared to its high prevalence in studies of NRTI regimens excluding AZT. 2010 Antiviral therapy Discussion HIV K65R 48 52 NRTI 140 144 20529865 Uncoating of human immunodeficiency virus type 1 requires prolyl isomerase Pin1. 2g and 3l, cell-based fate-of-capsid uncoating assay demonstrated that the infectivity defect of the S16A/P17A variant is linked to a dysfunction of the uncoating process, and Pin1 depletion in the target cells is linked to a dysfunction of uncoating. 2010 The Journal of biological chemistry Discussion HIV P17A;S16A 106;101 110;105 Capsid;PI 30;176 36;178 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. There was a high rate of VF in the small number of subjects with a M184V, even when the TDR was present at <20% levels of the quasispecies and missed by standard genotyping methods. 2010 PloS one Discussion HIV M184V 67 72 20532178 Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naive subjects in the CASTLE study. These results suggest that M184V and specific patterns of N(t)RTI mutation patterns may contribute to predicting response to a boosted PI regimen. 2010 PloS one Discussion HIV M184V 27 32 NRTI;PI 58;135 65;137 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Although K65R results in an increase in misinsertion fidelity, there is an additional decrease in mismatch extension from some termini, which is due to a 10-fold increase in dNTP Kd compared to the wild-type. 2010 Journal of molecular biology Discussion HIV K65R 9 13 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. As expected, the K65R substitution has no, or little, effect on the binding of either a correct or incorrect dNTP; one of the guanidinium nitrogens of the Arg65 residue is positioned to coordinate the incoming dNTP similarly to Lys65 in the wild type. 2010 Journal of molecular biology Discussion HIV K65R 17 21 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Both the K65A and K65R mutations lead to a decrease in mismatch extension efficiency compared to the wild-type enzyme. 2010 Journal of molecular biology Discussion HIV K65A;K65R 9;18 13;22 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Discrimination against misinsertion of pyrimidine dNTPs (with a pyrimidine template base) by K65A RT is due to a decrease in kpol and increased Kd; the decrease in dNTP binding affinity is the largest factor. 2010 Journal of molecular biology Discussion HIV K65A 93 97 RT 98 100 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. However the change in kpol caused by the K65A substitution suggests that after binding dGTP, the rate of the conformational change preceding the chemistry step is reduced, possibly due to the improper alignment of the incorrect dNTP with the template base. 2010 Journal of molecular biology Discussion HIV K65A 41 45 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. In RTs containing V75I, a secondary mutation associated with mutations conferring resistance to both ddNTPs and NNRTIs, there is an increase in incorporation fidelity and, to a greater degree, a decrease in efficiency of mismatch extension. 2010 Journal of molecular biology Discussion HIV V75I 18 22 NNRTI;RT 112;3 118;6 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. In the context of misinsertion, the Arg72, with less freedom of movement due to the K65R substitution, may be less able to coordinate the dNTP for optimal catalysis, hence reducing the kpol. 2010 Journal of molecular biology Discussion HIV K65R 84 88 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. K65R reduces sensitivity of HIV to tenofovir and ddNTPs, but is rarely selected as a result of drug treatment. 2010 Journal of molecular biology Discussion HIV K65R 0 4 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Several studies have shown that patient-derived or recombinant virus containing the K65R mutation has a lower replicative capacity than wild-type in cell culture (from ~20% to 60% that of wild type), but conflicting results have also been reported, showing that the K65R mutation does not grossly impact viral replicative capacity in cell culture, in either single- or multiple cycles of infection. 2010 Journal of molecular biology Discussion HIV K65R;K65R 84;266 88;270 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Similarly, K65R results in resistance to dideoxynucleotide inhibitors, and this has been shown to be due to a reduction in kpol; the K65R mutation also allows binding of dNDPs by RT, but the wild-type residue is required for incorporation. 2010 Journal of molecular biology Discussion HIV K65R;K65R 11;133 15;137 RT 179 181 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The difference in fidelity caused by the substitutions is almost entirely at the level of dNTP binding; on the purine-purine mismatched terminus, the K65R and K65A substitutions increase the dNTP Kd, compared to the wild-type, approximately 13-fold and 52-fold respectively. 2010 Journal of molecular biology Discussion HIV K65A;K65R 159;150 163;154 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The K65R mutation has a significant effect on kpol for misinsertion. 2010 Journal of molecular biology Discussion HIV K65R 4 8 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The K65R mutation has previously been demonstrated to result in an 8-fold increase in base substitution fidelity using a forward mutation assay. 2010 Journal of molecular biology Discussion HIV K65R 4 8 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The K65R mutation results in a decrease in kpol for the correct, natural dNTPs, but this does not seem to be sufficient to explain the lack of selection in vivo. 2010 Journal of molecular biology Discussion HIV K65R 4 8 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The loss of the interaction between Lys65 and the gamma-phosphate of the incoming dNTP in the K65A substituted RT will result in a greater dependency on other interactions in the dNTP-binding pocket to stabilize binding of the incoming nucleotide. 2010 Journal of molecular biology Discussion HIV K65A 94 98 RT 111 113 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The mechanism through which V75I acts is less clear, as the residue does not interact directly with the incoming dNTP, but does interact with the template overhang. 2010 Journal of molecular biology Discussion HIV V75I 28 32 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The proportion of errors made by the wild type enzyme at homopolymeric runs was higher than that of the K65R. 2010 Journal of molecular biology Discussion HIV K65R 104 108 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The recently solved ternary structure of K65R RT in complex with template-primer and an incoming dATP suggests that the K65R substitution locks the Arg72 side-chain into a particular orientation via a stacking interaction, and it was hypothesized that the structural constraint imposed by the K65R/Arg72 interaction could be involved in the higher fidelity of the K65R mutation. 2010 Journal of molecular biology Discussion HIV K65R;K65R;K65R;K65R 41;120;293;364 45;124;297;368 RT 46 48 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. The Y115W substitution also reduces dNTP binding affinity and decreases primer mismatch extension, although this effect can be somewhat mitigated by the presence of a primer-grip substitution, M230I. 2010 Journal of molecular biology Discussion HIV M230I;Y115W 193;4 198;9 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. This effect is clearly influenced by the particular base-pair at the mismatched terminus; by comparison, at a G:T mismatch the affinity of the K65R substituted RT for the next nucleotide was increased. 2010 Journal of molecular biology Discussion HIV K65R 143 147 RT 160 162 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Thus, following a misinsertion, the K65R substituted RT is less capable of extending the nascent strand than the wild-type enzyme, presumably reducing the overall replication efficiency and therefore viral fitness. 2010 Journal of molecular biology Discussion HIV K65R 36 40 RT 53 55 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Thus, stable binding of the incorrect dNTP in the active site would be less dependent on the hydrogen bond between the gamma-phosphate of the incoming dNTP and Lys65, and the K65A substitution has less effect on Kd. 2010 Journal of molecular biology Discussion HIV K65A 175 179 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. Using a forward mutation assay, in which substitution, deletion and insertion mutations were measured, the K65R mutation was found to increase RT fidelity by 8-fold through a decrease in all three types of error. 2010 Journal of molecular biology Discussion HIV K65R 107 111 RT 143 145 20538005 K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies. V148I and Q151N substitutions in reverse transcriptase also increase mismatch extension fidelity, producing mismatch extension efficiencies that approach the misinsertion efficiency; in contrast, the wild-type enzyme is 1-2 orders of magnitude more efficient in primer misextension than dNTP misinsertion. 2010 Journal of molecular biology Discussion HIV Q151N;V148I 10;0 15;5 RT 33 54 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Although UDPS detected K65R in a median of 1.0% of sequence reads of subtype C plasma samples, Sanger sequencing of limiting dilution and molecular clones from the two samples with the highest proportions of K65R strongly suggested that the UDPS data resulted from PCR error. 2010 PloS one Discussion HIV K65R;K65R 23;208 27;212 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. First, it shows that the RT KKK nucleotide template in subtype C viruses can lead to the spurious detection of K65R by highly sensitive PCR-dependent sequencing techniques such as UDPS or deep molecular clonal sequencing. 2010 PloS one Discussion HIV K65R 111 115 RT 25 27 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. For example, subtype C viruses are significantly more likely than subtype B viruses to develop the non-nucleoside RT-inhibitor-resistance mutation V106M because this mutation requires a single substitution for subtype C viruses (GTG ATG) but two substitutions for subtype B viruses (GTA ATG ). 2010 PloS one Discussion HIV V106M 147 152 RT 114 116 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. However, such a mechanism cannot explain a preference for K65R in subtype C viruses because a change from K to R requires a single substitution regardless of the underlying nucleotide template (AAA AGA or AAG AGG). 2010 PloS one Discussion HIV K65R 58 62 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Indeed, K65R was not detected by UDPS when the high fidelity PCR enzyme PfuUltra II Fusion was used. 2010 PloS one Discussion HIV K65R 8 12 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Second, our finding that the likelihood of identifying K65R varies with viral subtype is consistent with the work of Coutsinos et al. 2010 PloS one Discussion HIV K65R 55 59 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. The fact that codon 63 has an invariant ATA sequence is consistent with the idea that the increased likelihood of K65R is due to the stretch of six consecutive T's encountered during positive-strand DNA synthesis of subtype C (but not subtype B) templates. 2010 PloS one Discussion HIV K65R 114 118 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. These experiments also confirm that it was PCR error, rather than pyrosequencing that accounts for the spurious finding of K65R. 2010 PloS one Discussion HIV K65R 123 127 20539818 Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. Thus, even though naturally occurring K65R variants do not appear to be present in ARV-naive individuals at levels detectable by currently available deep sequencing technologies, we cannot exclude the possibility that the steady state levels of such variants are higher in subtype C compared with subtype B virus isolates. 2010 PloS one Discussion HIV K65R 38 42 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. Comparing the trajectories from MD simulations on the wild-type protease and the V82F/I84V protease variant, Perryman et al. 2010 Journal of chemical theory and computation Discussion HIV I84V;V82F 86;81 90;85 PR;PR 64;91 72;99 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. found that the mutation I84V has decreased the vdW interaction between APV and the drug-resistant variant, which might account for the loss of binding affinity between APV and the drug-resistant variant. 2010 Journal of chemical theory and computation Discussion HIV I84V 24 28 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. In the case of the ACT (V82T, I84V) mutant here, the TI method not only gave the more accurate predicted energy than the MM-PB/GBSA method, but also had better reproducibility and faster convergence (Figure 3, Figure 4). 2010 Journal of chemical theory and computation Discussion HIV I84V;V82T 30;24 34;28 20543885 Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV. In this study we performed MM-PB/GBSA calculations and free-energy component analysis of DRV-WT, DRV-FLAP+ (L10I, G48V, I54V, V82A) and DRV-ACT (V82T, I84V). 2010 Journal of chemical theory and computation Discussion HIV G48V;I54V;I84V;L10I;V82A;V82T 114;120;151;108;126;145 118;124;155;112;130;149 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. For instance, mutations such as S9X, V280X, and P453X had convincingly strong associations with HLA_B*13, _B*46, and _B*55, respectively (p<0.001; Table 1). 2010 PloS one Discussion HIV P453X;S9X;V280X 48;32;37 53;35;42 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. However, the long-term effects of the transmission of virus attenuated by CTL escape mutations remain unknown and these contact cases should be examined longitudinally to determine whether virological escape accompanies the reversion of the T242N escape mutation. 2010 PloS one Discussion HIV T242N 241 246 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Several lines of evidence indicate that TW10 is the most important target determining the viral load set point: TW10 is the earliest target during primary infection; and among all the described HLA-associated mutations, T242N is the earliest escape mutation that emerges during acute infections. 2010 PloS one Discussion HIV T242N 220 225 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. Supporting this explanation, we observed substantially lower plasma viral loads in the B*57/*5801-positive subjects with T242N but without the compensatory mutations (p = 0.012 by ANOVA; Figure 4). 2010 PloS one Discussion HIV T242N 121 126 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. The A*33-associated T242X and G248X mutations are widely known to be selected by HLA_B*57/*5801, so they are likely to be reflected in the linkage disequilibrium with B*58. 2010 PloS one Discussion HIV G248X;T242X 30;20 35;25 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. This is the first report indicating that the p24 T242N escape mutation from the B*57/*58 CTL has a significant impact on the HIV-1 viral load in CRF01_AE infections and that the mutations, H219 and M228, compensate for the crippling effect of T242N. 2010 PloS one Discussion HIV T242N 243 248 p24 45 48 20567513 HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load. We have also shown that the transmission of virus crippled by T242N might be associated with lower plasma viral loads in HLA-unmatched recipients, supporting a previous study of clade C infections. 2010 PloS one Discussion HIV T242N 62 67 20578491 Virologic and immunologic outcomes in HIV-infected Cambodian children after 18 months of highly active antiretroviral therapy (HAART). Resistance genotyping performed in 2 of these patients demonstrated mutations associated with resistance to lamivudine (M184V) and to non-nucleoside reverse transcriptase inhibitors (Y181C and G190A). 2010 The Southeast Asian journal of tropical medicine and public health Discussion HIV G190A;M184V;Y181C 193;120;183 198;125;189 NNRTI 134 170 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Although the G116E substitution occurred during long-term cultivation of human cells infected with NL-4/5S6/7SvifS, the viruses with G116E unexpectedly became resistant to CM TRIM5alpha-mediated restriction (Figures 4 and 5). 2010 Retrovirology Discussion HIV G116E;G116E 13;133 18;138 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Analysis of a series of CA mutants shown in Figures 4 and 5 clearly excluded the possibility that the impaired replicative capability of NL-4/5S6/7SvifS in human cells resulted from an increased sensitivity to human TRIM5alpha because a virus with the SIVmac L4/5 and L6/7 (4/5S6/7S) showed similar infectivity to the wild-type virus in the presence of human TRIM5alpha, and a virus with the SIVmac L4/5, L6/7, and G116E substitution (4/5SG116E6/7S) became more sensitive to human TRIM5alpha (Figure 5B). 2010 Retrovirology Discussion HIV G116E 415 420 Capsid 24 26 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Another possibility is that NL-4/5S6/7SvifS was restricted by a certain intrinsic restriction factor that was previously suggested to be present in human cells, and that the adapted virus could escape from this restriction by G116E substitution, since the G116E was acquired through the adaptation in human cells. 2010 Retrovirology Discussion HIV G116E;G116E 226;256 231;261 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Consistent with this hypothesis, NL-4/5SG116EvifS, a virus with an HIV-1 derived L6/7 and the G116E substitution, showed impaired growth in MT4 cells (data not shown). 2010 Retrovirology Discussion HIV G116E 94 99 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. However, the addition of G116E substitution did not facilitate the cleavage of Gag, and a small defect in Gag processing could only partially explain the attenuated growth of NL-4/5S6/7SvifS. 2010 Retrovirology Discussion HIV G116E 25 30 Gag;Gag 79;106 82;109 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Replacing the HIV-1 L6/7 (HNPPIP) of the CA with that of SIVmac239 (RQQNPIP) resulted in elongation of the loop by one amino acid, and it is reasonable to assume that the G116E substitution occurred to compensate the structural warp caused by the extended L6/7. 2010 Retrovirology Discussion HIV G116E 171 176 Capsid 41 43 20609213 A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. The precise reasons for the impaired replicative capability of NL-4/5S6/7SvifS and effect of G116E in human cells remain to be elucidated. 2010 Retrovirology Discussion HIV G116E 93 98 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. 0.15% for M184V compared to 0.07% for M184I) or that these mutations are associated with a higher fitness cost. 2010 PloS one Discussion HIV M184I;M184V 38;10 43;15 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. For the same reason we would have expected to find M184V, Y181C and Y188C, but not T215Y/F since the latter are double mutants compared to wild-type. 2010 PloS one Discussion HIV M184V;T215F;T215Y;Y181C;Y188C 51;83;83;58;68 56;90;90;63;73 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. However, Johnson et al developed sensitive real-time PCRs and estimated the absolute assay sensitivities on a clone as well as the natural occurrence of several resistance mutations, including M184V, Y181C, T215Y and T215F, in 138 treatment naive patients with samples collected before the ART era. 2010 PloS one Discussion HIV M184V;T215F;T215Y;Y181C 194;218;208;201 199;223;213;206 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In addition, in vitro studies have shown that the mutation rate from wild-type to M184I is more than four times higher than that to M184V, while the enzymatic efficiency of a RT with M184I is approximately 50% lower than that of a RT with M184V. 2010 PloS one Discussion HIV M184I;M184I;M184V;M184V 82;183;132;239 87;188;137;244 RT;RT 175;231 177;233 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In contrast, we did not find any significant pre-existence of the major drug resistance mutations M184V, Y181C, Y188C or T215Y/F. 2010 PloS one Discussion HIV M184V;T215F;T215Y;Y181C;Y188C 98;121;121;105;112 103;128;128;110;117 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. In this study we found significant levels of M184I (4 of 5 patients), T215I and/or T215A (4 of 5 patients) ranging from 0.02%-0.12% in plasma samples obtained before treatment was initiated. 2010 PloS one Discussion HIV M184I;T215A;T215I 45;83;70 50;88;75 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. It has been proposed that this initial appearance of M184I is due to the balance between mutational bias of RT and selective pressure. 2010 PloS one Discussion HIV M184I 53 58 RT 108 110 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. It is interesting to note that we found significant levels of M184I, but not M184V, before treatment in 4 of 5 patients. 2010 PloS one Discussion HIV M184I;M184V 62;77 67;82 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. One explanation for the absence of significant levels of M184V, Y181C and Y188C could be that the cut-off values were higher at these positions (e.g. 2010 PloS one Discussion HIV M184V;Y181C;Y188C 57;64;74 62;69;79 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Several possible explanations have been proposed for the transient occurrence of M184I. 2010 PloS one Discussion HIV M184I 81 86 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. The presence of M184I, T215I and T215A in treatment naive patients is somewhat expected since these drug resistance mutations only differ by one nucleotide from wild-type. 2010 PloS one Discussion HIV M184I;T215A;T215I 16;33;23 21;38;28 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Therefore, the bias for G-to-A mutations of HIV-1 works in favor for M184I, while the selective pressure for enzymatic efficiency selects for M184V. 2010 PloS one Discussion HIV M184I;M184V 69;142 74;147 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. This agrees with early data from 3TC mono-therapy studies where it was shown that M184I usually occurs transiently before being replaced by M184V, which is more fit in the presence of 3TC. 2010 PloS one Discussion HIV M184I;M184V 82;140 87;145 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. This was accompanied by a gradual increase in the prevalence of variants with specific linked drug resistance mutations (in particular variants with M184V+T215Y and M184V+L210W+T215Y) (Table 4. 2010 PloS one Discussion HIV L210W;M184V;M184V;T215Y;T215Y 171;149;165;155;177 176;154;170;160;182 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. Thus, there is a higher production rate of M184I than M184V since the wild-type methionine is coded ATG and the resistance mutations to isoleucine and valine are coded ATA and GTG, respectively. 2010 PloS one Discussion HIV M184I;M184V 43;54 48;59 20628644 Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. We have shown that the levels of preexisting drug resistance in plasma samples from treatment naive patients is very low and that several important drug resistance mutations (M184V, Y181C, Y188C and T215Y/F) were not detectable in pre-treatment samples, indicating that the natural occurrence of these mutations are below our detection limit. 2010 PloS one Discussion HIV M184V;T215F;T215Y;Y181C;Y188C 175;199;199;182;189 180;206;206;187;194 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. A third study found the G140A mutation in place of G140S in viruses that carried G148R substitution. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140A;G140S;G148R 24;51;81 29;56;86 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. As expected, the mutant viruses were fitter than wild-type in the presence of drug, with the N155H mutant being more fit than the Q148H mutant. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N155H;Q148H 93;130 98;135 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Clones with G140S/Q148H showed higher integrase-mediated replication capacity as compared to clones with Q148R or N155H alone; the G140S/Q148H clones also exhibited higher levels of raltegravir resistance. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140S;G140S;N155H;Q148H;Q148H;Q148R 12;131;114;18;137;105 17;136;119;23;142;110 IN 38 47 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. However, the G140S/Q148H double-mutant was fitter than the E92Q/N155H double mutant. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E92Q;G140S;N155H;Q148H 59;13;64;19 63;18;69;24 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. In that study, the appearance of viruses with the Q148R or N155H mutations initially was associated with reduced replication capacity, but replication capacity returned towards wild-type levels as Q148H and G140S mutations emerged. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140S;N155H;Q148H;Q148R 207;59;197;50 212;64;202;55 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. It would be interesting to compare the fitness of the G140A and S mutants in combination with the different codon 148 mutants. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140A 54 59 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. Site-directed mutants carrying N155H showed lower replication capacity than wild-type, but higher replication capacity than Q148H(R)(K). 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N155H;Q148H 31;124 36;129 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. That study showed that the N155H and Q148H(R)(K) mutations appear to be mutually exclusive. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N155H;Q148H 27;37 32;42 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The E92Q/N155H double-mutant had a lower replication capacity than the N155H mutant, whereas the G140S/Q148H mutant showed a replication capacity that was close to that of the wild-type control. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E92Q;G140S;N155H;N155H;Q148H 4;97;9;71;103 8;102;14;76;108 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The eventual predominance of the G140S/Q148H double mutant is explained in part by its greater fitness in the presence of drug as compared to other raltegravir-resistant mutants. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140S;Q148H 33;39 38;44 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The greater fitness of the N155H mutant as compared to Q148H in the presence of drug likely contributes to the earlier emergence of N155H mutants in the setting of raltegravir failure. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N155H;N155H;Q148H 27;132;55 32;137;60 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The N155H mutation results in reduced strand-transfer activity, whereas the E92Q mutation is associated with modest reductions in both 3'-processing and strand transfer activities of the enzyme; both activities of the enzyme are substantially reduced in the G140S/Q148H mutant Whether these alterations in integrase function and the associated reductions in viral fitness and replication capacity are manifested clinically by lower level viremia at the time of raltegravir failure remains uncertain, as no consistent pattern has emerged in the examples reported to date. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E92Q;G140S;N155H;Q148H 76;258;4;264 80;263;9;269 IN 306 315 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The results of growth competition assays showed that in the absence of drug, the Q148H and N155H mutations, which confer raltegravir resistance, are associated with a substantial reduction in viral fitness as compared to wild-type. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N155H;Q148H 91;81 96;86 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. The secondary mutation E92Q occurred only in combination with N155H, whereas the G140S mutation occurred only with Q148H(R)(K). 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E92Q;G140S;N155H;Q148H 23;81;62;115 27;86;67;120 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. These results are consistent with the patterns of raltegravir resistance observed in samples from patients with virologic failure on a raltegravir-containing regimen, and suggest that N155H mutants emerge first because they are fitter than the N148H mutants. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N148H;N155H 244;184 249;189 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. These results are generally similar to the results of our study using growth competition experiments in the absence of drug, except that the E92Q/N155H mutant showed greater fitness than the N155H single mutant. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E92Q;N155H;N155H 141;146;191 145;151;196 20634701 Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. With the addition of the G140S mutation the G140S/N148H mutants enjoy a substantial fitness advantage over other raltegravir-resistant mutants and therefore become the dominant species in the virus population. 2010 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140S;G140S;N148H 25;44;50 30;49;55 20649426 Effect of acyclovir on HIV-1 set point among herpes simplex virus type 2-seropositive persons during early HIV-1 infection. However, the V75I mutation has a significant fitness cost, and it is possible that any selective advantage conferred by acyclovir resistance did not outweigh the fitness cost at the lower dose of acyclovir used in this study. 2010 The Journal of infectious diseases Discussion HIV V75I 13 17 20649426 Effect of acyclovir on HIV-1 set point among herpes simplex virus type 2-seropositive persons during early HIV-1 infection. Our finding contrasts with those of in vitro studies which used very high doses of acyclovir in HIV infectivity models with activated CD4 T cells or tonsillar lymphoid explants and found V75I and other mutations in HIV-1 reverse transcriptase that may confer resistance to some nucleoside reverse transcriptase inhibitors (NRTIs) used to treat HIV-1 infection. 2010 The Journal of infectious diseases Discussion HIV V75I 187 191 NRTI;RT;NRTI 278;221;323 310;242;328 HIV infections;HIV infections 96;344 111;359 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Also, the structure of PRG48V-DRV showed reduced volume of the active site cavity relative to the wild type complex, consistent with a major effect of the G48V rather than the L90M mutation in reducing the S1/S1' volume in PRG48V/L90M-SQV. 2010 The FEBS journal Discussion HIV G48V;G48V;L90M;L90M 155;225;176;230 159;229;180;234 PR;PR 23;223 25;225 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Besides the different interactions between PR and inhibitors, the absence of the C-H O contact between flap residue 50 and Thr80 in PRI50V-APV, and its presence in PRI50V-SQV and PRWT complexes, contributes to the drug resistance of this mutation. 2010 The FEBS journal Discussion HIV I50V 168 172 PR;PR;PR 43;134;166 45;136;168 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. Comparison of the structures provides insight into why I50V is a major drug resistant mutation observed on exposure to APV but appears less critical in resistance to SQV therapy. 2010 The FEBS journal Discussion HIV I50V 55 59 20695887 Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. No evidence was found, however, that PRL90M-APV had substantially altered the volume of the S1/S1' substrate binding pockets, unlike the PRG48V/L90M-SQV structure, which showed reduced volume for the S1/S1' subsites relative to the wild type complex. 2010 The FEBS journal Discussion HIV L90M 144 148 PR;PR 37;137 39;139 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. By altering these factors such as RT activity and cellular dNTP concentrations, we were able to detect the specific interplay of the cPPT sequence with the 3TC resistance of the M184I HIV-1 vector. 2010 Virology Discussion HIV M184I 178 183 RT 34 36 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. However, the cPPT inactivation did not affect the sensitivity of the M184I (-) cPPT vector to AZT. 2010 Virology Discussion HIV M184I 69 74 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. However, this drug sensitization effect seen with the M184I (-) cPPT vector was observed only with 3TC, not AZT or Nevirapine. 2010 Virology Discussion HIV M184I 54 59 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Importantly, the M184I mutant vector lost its 3TC resistance upon the cPPT inactivation. 2010 Virology Discussion HIV M184I 17 22 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Importantly, unlike 3TC, the low concentrations of AZT in this study (<6 microM) were sufficient to inhibit the replication of the M184I vector because the M184I RT is still sensitive to 3TCTP like WT RT, and the treatment with the low AZT concentration should not affect the cellular dNTP (dTTP) pools. 2010 Virology Discussion HIV M184I;M184I 131;156 136;161 RT;RT 162;201 164;203 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. In this study, we did not conduct experiments with the M184V RT vector, because, unlike M184I RT, the pre-steady state kinetic analysis demonstrated that M184V RT has a WT RT level of the dNTP binding affinity. 2010 Virology Discussion HIV M184I;M184V;M184V 88;55;154 93;60;159 RT;RT;RT;RT 61;94;160;172 63;96;162;174 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Indeed, we observed that only the elevation of dCTP, not the other three NTPs, abolished the sensitivity of the M184I (-) cPPT vector to 3TC. 2010 Virology Discussion HIV M184I 112 117 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Interestingly, a slight decrease of the NEV sensitivity was induced by the cPPT inactivation in the M184I vector. 2010 Virology Discussion HIV M184I 100 105 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. It can be presumed that by increasing intracellular dNTP pools, the M184I vector is rescued from its dNTP binding defect. 2010 Virology Discussion HIV M184I 68 73 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. One possible cause for this specificity could be the use of high concentrations of 3TC during the drug titration curves of the M184I vector. 2010 Virology Discussion HIV M184I 127 132 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. One would expect that the M184I (-) cPPT vector would become more sensitive to AZT because, like 3TC, AZT is a nucleoside analog that also requires phosphorylation by cellular machinery. 2010 Virology Discussion HIV M184I 26 31 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Our data demonstrates that the cPPT inactivation and the M184I RT mutation additively reduce the vector transduction efficiency and proviral DNA synthesis kinetics. 2010 Virology Discussion HIV M184I 57 62 RT 63 65 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Second, unlike M184I RT, WT HIV-1 RT is highly functional even at low dNTP concentrations. 2010 Virology Discussion HIV M184I 15 20 RT;RT 21;34 23;36 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Therefore, considering M184V RT in terms of its dNTP binding affinity, we postulate that cPPT removal should not significantly affect the 3TC resistance of the M184V vector even though the treatment with high concentrations of 3TC may restrict the cellular dNTP pools. 2010 Virology Discussion HIV M184V;M184V 23;160 28;165 RT 29 31 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Therefore, we believe the sensitivity to 3TC observed is exclusive to the M184I (-) cPPT vector. 2010 Virology Discussion HIV M184I 74 79 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. This biochemical data also explains why the M184I RT further mutates to M184V during the 3TC treatment. 2010 Virology Discussion HIV M184I;M184V 44;72 49;77 RT 50 52 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. This reduction is partially rescued by elevating both cellular dNTP concentrations and viral DNA polymerization capacity by incorporating WT RT molecules to the M184I vector. 2010 Virology Discussion HIV M184I 161 166 RT 141 143 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. Thus this data supports the idea that, instead of the direct replication inhibition induced by the 3TCTP incorporation, the cellular dCTP limitation induced by the high concentration of 3TC may be a cause of the replication restriction of the M184I vector especially when the replication kinetic role of cPPT is inactivated by the cPPT mutation. 2010 Virology Discussion HIV M184I 243 248 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. We were also able to demonstrate that the cPPT could compensate for the delayed proviral DNA synthesis induced by dNTP defective binding RT mutants such as Q151N and V184I. 2010 Virology Discussion HIV Q151N;V184I 156;166 161;171 RT 137 139 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. While it is possible that the delayed replication by the cPPT inactivation may be further delayed by the reduction of the enzymatically capable free M184I RTs induced by NEV binding, this effect appears to be minimal. 2010 Virology Discussion HIV M184I 149 154 RT 155 158 20701944 Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity. WT RT is able to synthesize proviral DNA efficiently even at very low dNTP concentrations due to its high binding affinity to dNTPs, but the limited dNTP pools induced by the treatment with high 3TC concentrations would affect the M184I RT due to its reduced dNTP binding affinity. 2010 Virology Discussion HIV M184I 231 236 RT;RT 3;237 5;239 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. D64V is a point mutation in the catalytic domain of HIV-1 integrase that is able to significantly reduce the occurrence of integration of vector-delivered genetic materials into target cell genomes. 2010 Vaccine Discussion HIV D64V 0 4 IN 58 67 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. In this present study, SVGmu-pseudotyped FUGW packaged with the defective integrase harboring the D64V mutation (FUGW/SVGmu(IN-)) was able to mediate transient GFP expression in HEK293T cells expressing hDC-SIGN, while it sustained stable GFP expression in BMDCs over three weeks, presumably due to the poorly proliferative nature of this cell type. 2010 Vaccine Discussion HIV D64V 98 102 IN;IN 74;124 83;126 20709004 Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity. The SVGmu envelope is involved in directing the vector to the DC-SIGN receptor to induce endocytosis, followed by mediating the release of the viral core from endosomes in a pH-dependent manner, whereas the D64V integration mutation prohibits vector integration of reversely transcribed proviral DNA. 2010 Vaccine Discussion HIV D64V 207 211 Env 10 18 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. An in-silico study of N155H and Q148H/R/K demonstrated that the structure of flexible loop (residues 140-148) in catalytic domain is conserved suggesting IN would be catalytically active. 2010 Biochemistry Discussion HIV N155H;Q148H;Q148K;Q148R 22;32;32;32 27;41;41;41 IN 154 156 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. An interesting observation was the susceptibility of N155H to MK-2048 and RDS 2197. 2010 Biochemistry Discussion HIV N155H 53 58 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Comprehensive in vitro mutagenesis and computational studies of the flexible loop in HIV-1 IN accounted for most of the observed phenotypes of N155H and Q148H/R/K mutations in these RAL resistant viruses. 2010 Biochemistry Discussion HIV N155H;Q148H;Q148K;Q148R 143;153;153;153 148;162;162;162 IN 91 93 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. IN derived from HXB2-IIIB strain containing N155H substitution also possessed nearly two third of concerted integration activity compared to its wt counterpart. 2010 Biochemistry Discussion HIV N155H 44 49 IN 0 2 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In other studies with his-tag IN containing the N155H mutation, the catalytic activities using oligonucleotide DNA substrates demonstrated were ~5 to 35% relative to wt IN suggesting, the presence of the tag or purification conditions affected the observed activities. 2010 Biochemistry Discussion HIV N155H 48 53 IN;IN 30;169 32;171 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In our study, IN containing the Q148H mutation possessed nearly 30% activity for concerted integration relative to wt IN although it produced nearly 60-70% of CHS product compared to wt IN (Supporting Information, Figure S1). 2010 Biochemistry Discussion HIV Q148H 32 37 IN;IN;IN 14;118;186 16;120;188 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. In summary, the assembly properties for SC of IN containing N155H and Q148H mutations in vitro correlates with their replication capacities in vivo. 2010 Biochemistry Discussion HIV N155H;Q148H 60;70 65;75 IN 46 48 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. IN with the N155H mutation possessed ~70% capacity of wt IN for both SC assembly (Figure 6B and 6D) and concerted integration activity (Figure 6E) although, the kinetics of N155H for these events was slower (Figures 6). 2010 Biochemistry Discussion HIV N155H;N155H 12;173 17;178 IN;IN 0;57 2;59 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. MK-2048 had a dissociation half-life of nearly 4 h and 32 h with N155H IN and wt IN, respectively. 2010 Biochemistry Discussion HIV N155H 65 70 IN;IN 71;81 73;83 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. MK-2048 had similar potency against wt IN and N155H with a low IC50 value of 42 nM for inhibiting concerted integration (Table 1). 2010 Biochemistry Discussion HIV N155H 46 51 IN 39 41 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. Similar susceptibility (1.3 fold) of IN with the N155H mutation to RDS 2197 compared to wt IN to inhibit concerted integration was evident (Figure 8C)(Table 1). 2010 Biochemistry Discussion HIV N155H 49 54 IN;IN 37;91 39;93 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The dissociation half-life of RAL with an N155H IN-DNA complex was nearly 0.7 h as compared to 7.3 h with wt IN-DNA complex. 2010 Biochemistry Discussion HIV N155H 42 47 IN;IN 48;109 50;111 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The IC50 value for EVG with the N155H mutant to inhibit concerted integration was nearly 10-fold higher than wt IN (Figure 8C) similar to earlier studies using DNA oligonucleotides substrates. 2010 Biochemistry Discussion HIV N155H 32 37 IN 112 114 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The N155H substitution provided varying degrees of cross-resistance to different STIs. 2010 Biochemistry Discussion HIV N155H 4 9 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. The relative longer half-life of MK-2048 in IN-DNA complexes could be a plausible reason for enhanced potency for inhibiting IN with the N155H mutation. 2010 Biochemistry Discussion HIV N155H 137 142 IN;IN 44;125 46;127 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. These data suggest the 3'-OH processing by IN having Q148H mutation was not severely affected under these assay conditions. 2010 Biochemistry Discussion HIV Q148H 53 58 IN 43 45 20799722 Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors. This study suggests a correlation exists between the physical trapping of SC with the potency for inhibiting concerted integration using wt IN as well as N155H and Q148H. 2010 Biochemistry Discussion HIV N155H;Q148H 154;164 159;169 IN 140 142 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. However this is a controversial observation, more recently challenged by studies reporting that the mutation R77Q can't be associated to reduce HIV-1 infectivity. 2010 PloS one Discussion HIV R77Q 109 113 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. In contrast the double substitution, R77A and R80A, allowed the binding to PP2A1 holoenzyme. 2010 PloS one Discussion HIV R77A;R80A 37;46 41;50 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. In contrast the DPT-Vpr2 peptide that contains the IQQ/VTR83-85 and T89A substitutions is unable to deliver streptavidin-HRP molecules into HeLa cells. 2010 PloS one Discussion HIV T89A 68 72 Vpr 20 23 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. Interestingly the R80A substitution renders also Vpr inactive for cell cycle arrest but the R77A and R80A substitutions that affect direct binding of Vpr 71-82 to ANT and inactivate the michondriontoxic domain activity did not prevented apoptosis induction. 2010 PloS one Discussion HIV R77A;R80A;R80A 92;18;101 96;22;105 Vpr;Vpr 49;150 52;153 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. It was previously published that the mutation R77Q of HIV-1 Vpr frequently occurs in HIV-1 infected Long Term Non Progressor (LTNP) patients. 2010 PloS one Discussion HIV R77Q 46 50 Vpr 60 63 HIV infections 85 99 21072166 PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. We found that the IIQ/VTR83-85 substitutions or the single residue substitution I84P prevented the PP2A1 binding. 2010 PloS one Discussion HIV I84P 80 84 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. A GRT had not been performed at the time of first HIV diagnosis, so straightforward evidence could not be provided to exclude the presence of the K103N mutation in our patient in advance of his first line HAART. 2009 Journal of medical case reports Discussion HIV K103N 146 151 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. As a consequence, although both the existence and the transmission of HIV strains carrying the K103N mutation in NNRTI-naive patients have been extensively documented, it is unlikely that our patient may have been infected with an HIV strain carrying the K103N mutation, as the widespread use of NNRTIs in Italy began after 1996. 2009 Journal of medical case reports Discussion HIV K103N;K103N 95;255 100;260 NNRTI;NNRTI 113;296 118;302 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Collins et al., applied a fitness assay to several NNRTI drug-resistant quasispecies, demonstrating that the wild type had a better fitness than K103N-bearing quasispecies, and that the fitness rank for other NNRTI mutation-carrying quasispecies was 181C > 190A > 188C > 106A. 2009 Journal of medical case reports Discussion HIV K103N 145 150 NNRTI;NNRTI 51;209 56;214 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. In one patient, strains carrying K103N mutation persisted for six years as dominant quasispecies, in the absence of selective pressure, after administration of EFV for a year and a half. 2009 Journal of medical case reports Discussion HIV K103N 33 38 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. In our patient, persistence of the K103N-containing quasispecies ensued after a short exposure to EFV, in the absence of any further selective pressure. 2009 Journal of medical case reports Discussion HIV K103N 35 40 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. reported on the persistence of K103N mutation after EFV interruption in patients failing to EFV-containing regimens, documenting variable decay kinetics for the K103N containing quasispecies. 2009 Journal of medical case reports Discussion HIV K103N;K103N 31;161 36;166 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. reported the case of a HIV-infected woman who, seven years after exposure to a failing loviride-containing HAART regimen, presented the K103N mutation at a later viral relapse, without further exposure to any NNRTI selective pressure for as long as seven years after loviride. 2009 Journal of medical case reports Discussion HIV K103N 136 141 NNRTI 209 214 HIV infections 23 35 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Reports on such women, however, indicate that the K103N quasispecies were present as a minority quasispecies in most described cases. 2009 Journal of medical case reports Discussion HIV K103N 50 55 21092074 Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature. Therefore, it is more likely that exposure to EFV monotherapy at the time of therapy interruption selected the K103N mutation, which persisted as the prevalent quasispecies for over 3 years of continual viral replication, in the absence of selective pressure. 2009 Journal of medical case reports Discussion HIV K103N 111 116 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. As expected, M184V was the most common NRTI-associated mutation, emerging as early as after 1.5 months of failure and persisting at nearly every time point tested (38 of 40). 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 13 18 NRTI 39 43 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. Etravirine was designed for use in patients who had failed first generation NNRTI's, retaining activity in the context of K103N. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 122 127 NNRTI 76 81 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. For HIV subtype B, the M184V, L74V and Y181C mutations partially re-sensitize TAM containing viruses to thymidine analogues. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV L74V;M184V;Y181C 30;23;39 34;28;44 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. In contrast to M184V, TAMs generally arise after long periods of virological failure. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 15 20 21099693 Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. M184V has been shown to emerge in high prevalence among children and adults failing on 3TC-containing regimens in developed countries; cross-sectional studies have likewise reported a high prevalence of M18V among African (63-69%) and Thai (84-85%) children. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M18V;M184V 203;0 207;5 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Furthermore, expression of L10I caused less protease induced death than WT protease, more than I54V and V82A, albeit neither difference reached significance. 2010 PLoS pathogens Discussion HIV I54V;L10I;V82A 95;27;104 99;31;108 PR;PR 44;75 52;83 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. In this light it is of great interest that I54V and V82A have evidence of having co-evolved; possibly by virtue of cooperative selection due to low Casp8p41 production. 2010 PLoS pathogens Discussion HIV I54V;V82A 43;52 47;56 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Indeed the combined effect of mutations which impair protease cytotoxic effects (e.g., I54V and V82A) along with other mutations that do not (e.g., L63P, L90M) will need to be individually assessed. 2010 PLoS pathogens Discussion HIV I54V;L63P;L90M;V82A 87;148;154;96 91;152;158;100 PR 53 61 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. The mutation L10I is also of interest, in that it caused an intermediate degree of procaspase 8 cleavage generating less Casp8p41 than WT protease, but more than I54V and V82A (data not shown). 2010 PLoS pathogens Discussion HIV I54V;L10I;V82A 162;13;171 166;17;175 PR 138 146 21124822 Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells. Those studies show that the mutations I54V and V82A cause less procaspase 8 cleavage, less Casp8p41 production, and impaired induction of cell death following isolated protease expression or HIV infection. 2010 PLoS pathogens Discussion HIV I54V;V82A 38;47 42;51 PR 168 176 HIV infections 191 204 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. First, the magnitude of the backward mutation rate of V38A is approximately the same as that of the forward mutation rate. 2010 PLoS computational biology Discussion HIV V38A 54 58 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. It should be noted that in the experiment only the proportion of V38A was measured, and so there might be other mutant virus resistant to ENF that would have been included in the ENF-sensitive viral load. 2010 PLoS computational biology Discussion HIV V38A 65 69 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. The model was used to fit data concerning the level of ENF-sensitive viruses, V38A ENF-resistant viruses and the CD4+ T cell count from HIV-1 infected patients, who underwent ENF interruption and subsequent re-administration while continuing to receive the other drugs in their regimen. 2010 PLoS computational biology Discussion HIV V38A 78 82 HIV infections 136 150 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. This reduced fitness of V38A ENF-resistant virus agrees with the experimental finding of reduced fitness of the V38A mutant virus compared to wild-type virus in vitro. 2010 PLoS computational biology Discussion HIV V38A;V38A 24;112 28;116 21124866 Treatment-mediated alterations in HIV fitness preserve CD4+ T cell counts but have minimal effects on viral load. We have considered the V38A mutant virus as a representative of all ENF-resistant viruses. 2010 PLoS computational biology Discussion HIV V38A 23 27 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. In a single cell HIV-1 infectivity assay, virus with the V75I mutation demonstrated phenotypic resistance to acyclovir. 2011 The Journal of infectious diseases Discussion HIV V75I 57 61 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. In one of these reports, HIV-1 culture in the presence of acyclovir resulted in selection of a specific HIV-1 RT mutation (V75I) that became the predominant genotype by 94 days. 2011 The Journal of infectious diseases Discussion HIV V75I 123 127 RT 110 112 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. In this prospective evaluation of HIV-1/HSV-2 dually-infected men and women from Botswana, Kenya, Peru, and the US exposed to daily HSV-2 suppressive therapy for between 8 weeks and 24 months, we found no evidence of selection of HIV-1 genotypic resistance, specifically the V75I substitution. 2011 The Journal of infectious diseases Discussion HIV V75I 275 279 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. Our study is the among the first assessments of whether standard doses of acyclovir and valacyclovir suppressive therapy select for specific HIV-1 resistance mutations in vivo, and our results thus do not confirm in vitro studies that found that high-dose acyclovir had direct anti-HIV-1 activity and selected V75I mutants resistant to acyclovir. 2011 The Journal of infectious diseases Discussion HIV V75I 310 314 21148504 Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. The mutations selected in the in vitro experiments confer cross-resistance to NRTIs: V75I contributes resistance to multiple NRTIs in the presence of a concurrent Q151M mutation, T69N and other variants at position 69 are selected by didanosine and other NRTIs but their susceptibility profiles are not well-described (http://hivdb.stanford.edu/), and the variants M184I/V confer high-level resistance to lamivudine and emtricitabine. 2011 The Journal of infectious diseases Discussion HIV M184I;M184V;Q151M;T69N;V75I 365;365;163;179;85 372;372;168;183;89 NRTI;NRTI;NRTI 78;125;255 83;130;260 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Although the ion-channel activity of the Vpu-I17A has not been determined, Vpu-I17A effectively enhanced virion release and down-regulated BST-2 from the cell surface. 2011 Virology Discussion HIV I17A;I17A 45;79 49;83 Vpu;Vpu 41;75 44;78 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Although the ion-channel activity of Vpu-A18H has not been determined, its presence in a SHIV background rendered the virus susceptible to rimantadine when used at high concentrations during spreading infections. 2011 Virology Discussion HIV A18H 41 45 Vpu 37 40 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Altogether, these data suggest that the primary defect in Vpu-A18H is subcellular mislocalization. 2011 Virology Discussion HIV A18H 62 66 Vpu 58 61 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Blocking the egress of proteins from the ER by treating cells with BFA largely mimicked the effect of the A18H substitution. 2011 Virology Discussion HIV A18H 106 110 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Furthermore, Vpu-A18H was not completely devoid of virologic activity; rather it enhanced virion release by only 2-fold compared to the 7- to 8-fold increase observed for the wild type protein. 2011 Virology Discussion HIV A18H 17 21 Vpu 13 16 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Furthermore, Vpu-I17A exhibited a similar subcellular distribution to wild type Vpu and co-localized with BST-2 within endosomes. 2011 Virology Discussion HIV I17A 17 21 Vpu;Vpu 13;80 16;83 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. GxxxG and AxxxA motifs are thought to facilitate backbone interactions between alpha-helixes within lipid bilayers, and so the A18H substitution could potentially affect directly the interaction with BST-2. 2011 Virology Discussion HIV A18H 127 131 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. How does a single amino acid substitution in the TMD affect the steady-state subcellular localization of Vpu? Structural analysis of the Vpu TMD in artificial lipid bilayers suggests that the A18H substitution increases the length of the alpha-helical TMD. 2011 Virology Discussion HIV A18H 192 196 Vpu;Vpu 105;137 108;140 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. However, since Vpu-A18H co-localized poorly with BST-2, an alternative explanation is that the A18H substitution directly disrupts the reported interaction between the two proteins. 2011 Virology Discussion HIV A18H;A18H 19;95 23;99 Vpu 15 18 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In contrast to histidine, the substitution of A18 with phenylalanine (Vpu-A18F) minimally disrupted Vpu activity. 2011 Virology Discussion HIV A18F 74 78 Vpu;Vpu 70;100 73;103 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. In this regard, computational modeling indicated that Vpu-A18H has the potential to interact with BST-2 via its TMD, although the interaction is predicted to be somewhat less stable than wild type Vpu. 2011 Virology Discussion HIV A18H 58 62 Vpu;Vpu 54;197 57;200 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Nevertheless, Vpu-W22L efficiently down-regulated BST-2 from the cell surface; it efficiently enhanced virion release; and it co-localized extensively with BST-2. 2011 Virology Discussion HIV W22L 18 22 Vpu 14 17 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Remarkably, a precedent exists for the ER-retention induced by the A18H substitution: the introduction of single charged residues or histidines within the TMD of the IL-2 receptor alpha chain (Tac antigen), a protein normally resident on the plasma membrane, induces ER-retention, although the mechanism of this effect is obscure. 2011 Virology Discussion HIV A18H 67 71 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Similarly, the increased tilt angle of the Vpu-A18H TMD could potentially disrupt the interaction with BST-2. 2011 Virology Discussion HIV A18H 47 51 Vpu 43 46 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Since the ER, Golgi, and plasma membranes are of unequal thickness due to different contents of cholesterol, a change in TMD length could conceivably alter the accessibility of Vpu-A18H to different membrane compartments, but shorter rather than longer TMD lengths are associated with retention in the ER. 2011 Virology Discussion HIV A18H 181 185 Vpu 177 180 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Strikingly, Vpu-S23L was previously characterized as defective for ion-channel activity, yet it robustly down-regulated BST-2 from the cell surface; it enhanced virion release to the same extent as wild type Vpu; and it co-localized and interacted with BST-2. 2011 Virology Discussion HIV S23L 16 20 Vpu;Vpu 12;208 15;211 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The frequency of the polymorphism I17A was the highest of the four mutants tested (8%), supporting our observations that the I17A substitution does not adversely affect Vpu function. 2011 Virology Discussion HIV I17A;I17A 34;125 38;129 Vpu 169 172 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. The I17A substitution studied here was intended to affect a hinge region or kink in the Vpu TMD alpha-helix. 2011 Virology Discussion HIV I17A 4 8 Vpu 88 91 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. This conservation suggests that the very subtle defects of Vpu-W22L in the down-regulation of BST-2 from the cell surface and in the enhancement of virion release may be important in vivo. 2011 Virology Discussion HIV W22L 63 67 Vpu 59 62 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. This result seems at some odds with the data herein, in which the A18H substitution itself impaired Vpu's ability to enhance virion release, even in the absence of an adamantane. 2011 Virology Discussion HIV A18H 66 70 Vpu 100 103 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. To reconcile these findings, we note that Vpu-A18H retained a modest ability to down-regulate BST-2 from the cell surface at the very highest levels of transfection (as measured by GFP intensity). 2011 Virology Discussion HIV A18H 46 50 Vpu 42 45 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Unexpectedly, microscopic data indicated that Vpu-A18H remains largely trapped in the ER and fails to efficiently access the trans-Golgi network and the endosomal system. 2011 Virology Discussion HIV A18H 50 54 Vpu 46 49 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-A18H was first conceived to mimic the Influenza virus M2 protein ion-channel and allow Vpu's channel activity to be modulated by adamantane drugs. 2011 Virology Discussion HIV A18H 4 8 Vpu;Vpu 0;91 3;94 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Vpu-W22L was previously characterized as a functional ion-channel, although rather than oscillating rapidly between open and closed conformations, the transitions between the two conformations are prolonged. 2011 Virology Discussion HIV W22L 4 8 Vpu 0 3 21237475 BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. We show here that a single amino acid substitution in the transmembrane domain of Vpu (A18H) is sufficient to cause abnormal retention of the protein in the ER. 2011 Virology Discussion HIV A18H 87 91 Vpu 82 85 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Also, Q151M and associated mutations A62V, V75I, and F77L are likely to modify the hydrophobic core of the fingers. 2011 PloS one Discussion HIV A62V;F77L;Q151M;V75I 37;53;6;43 41;57;11;47 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. However, we believe that similar to K65R, its prevalence will increase, as tenofovir use continues to rise. 2011 PloS one Discussion HIV K65R 36 40 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Importantly, K70Q/Q151Mc is 10 times less susceptible to TFV-DF than WT HIV-1, whereas the CCOs for TFV-DF is defined as a 2.1-fold reduction in virologic response to this inhibitor. 2011 PloS one Discussion HIV K70Q 13 17 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. In addition to the clinical and virological studies, we used biochemical techniques to determine the mechanism of TFV resistance imparted by the K70Q mutation to Q151Mc RTs. 2011 PloS one Discussion HIV K70Q 145 149 RT 169 172 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. In our case, a new mutation (K70Q) was identified in a patient infected with Q151Mc HIV-1 during the course of TFV-DF-based antiviral therapy. 2011 PloS one Discussion HIV K70Q 29 33 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. In summary, we report here clinical data showing that addition of the K70Q mutation to the Q151Mc background confers high-level HIV resistance to TFV-DF and enhances resistance to other NRTIs. 2011 PloS one Discussion HIV K70Q 70 74 NRTI 186 191 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. K70R is a key mutation involved in resistance to AZT and appears in the background of other excision enhancement mutations. 2011 PloS one Discussion HIV K70R 0 4 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. K70T emerged in the background of Q151Mc during in vitro selection by TFV-DF. 2011 PloS one Discussion HIV K70T 0 4 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Moreover, K70Q/Q151Mc is at least twice as resistant to TFV as the well-known TFV-resistant K65R in the background of Q151Mc (as reported in the Stanford HIV Drug Resistance Database). 2011 PloS one Discussion HIV K65R;K70Q 92;10 96;14 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Mutations at position 70 of RT have been known to confer NRTI resistance by two distinct mechanisms: K70R combined with at least two excision enhancing mutations, D67N and T215Y, enhances ATP-mediated excision of AZT and d4T (excision-dependent mechanism). 2011 PloS one Discussion HIV D67N;K70R;T215Y 163;101;172 167;105;177 NRTI;RT 57;28 61;30 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. On the other hand, K70E causes resistance to 3TC, TFV, and ABC by lowering the maximum rate of inhibitor incorporation by RT (kpol-dependent exclusion mechanism). 2011 PloS one Discussion HIV K70E 19 23 RT 122 124 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Ongoing crystallographic studies are expected to provide more detailed structural insights into the role of K70Q in drug resistance. 2011 PloS one Discussion HIV K70Q 108 112 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Our results establish that in the background of Q151Mc, K70Q causes TFV resistance through a third mechanism: by decreasing the binding affinity of the inhibitor (Kd-dependent exclusion mechanism). 2011 PloS one Discussion HIV K70Q 56 60 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Our study has unambiguously demonstrated that K70Q meets at least the first three criteria: evidence for criterion #1 is shown in Figure 2; for criterion #2 in Figures 1 and 2; and for criterion #3 in Figure 1 and Figure S1. 2011 PloS one Discussion HIV K70Q 46 50 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Our virological studies with recombinant viruses confirmed that the observed enhancement and expansion of multi-drug resistance is the consequence of the addition of K70Q to Q151Mc HIV. 2011 PloS one Discussion HIV K70Q 166 170 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Previous studies have offered insights into the drug resistance mechanism of similar mutations (K70E, K70G, K70R, and K70T). 2011 PloS one Discussion HIV K70E;K70G;K70R;K70T 96;102;108;118 100;106;112;122 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Similarly, clinical isolates deposited at the Stanford HIV resistance database and carrying the Q151Mc mutation were also susceptible to TFV-DF, unless they also had the K65R mutation. 2011 PloS one Discussion HIV K65R 170 174 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Specifically, K70E was selected in patients with virological failure after TFV-DF-based antiviral therapy. 2011 PloS one Discussion HIV K70E 14 18 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. The K70Q/Q151Mc set of mutations is currently rare among HIV-infected patients. 2011 PloS one Discussion HIV K70Q 4 8 HIV infections 57 69 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Therefore, the K70Q mutation meets the criteria of a clinically relevant mutation. 2011 PloS one Discussion HIV K70Q 15 19 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. To gain insights into the possible structural changes caused by the addition of K70Q to Q151Mc, we compared the molecular model of K70Q/Q151Mc RT/DNA/TFV-DP with the crystal structure of WT RT/DNA/TFV-DP. 2011 PloS one Discussion HIV K70Q;K70Q 80;131 84;135 RT;RT 143;190 145;192 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. Using transient-state kinetics we unambiguously established that the overall mechanism of K70Q/Q151Mc resistance to TFV is due to enhanced discrimination between the natural dATP substrate and TFV-DP. 2011 PloS one Discussion HIV K70Q 90 94 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. We demonstrate here that Q151Mc can acquire an additional mutation, K70Q, which expands the multi-drug resistance to include high-level resistance to TFV-DF. 2011 PloS one Discussion HIV K70Q 68 72 21249155 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism. We used primer extension assays to show that K70Q/Q151Mc RT is less susceptible to TFV-DP than WT and Q151Mc RTs. 2011 PloS one Discussion HIV K70Q 45 49 RT;RT 57;109 59;112 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. A recent study comparing binary structures of WT and M184I RTs showed that Ile mutation at position 184 with a longer and more rigid beta-branched side chain possibly deforms the shape of the dNTP binding pocket which can restrict dNTP binding resulting in inefficient DNA synthesis at low dNTP concentrations. 2011 Virology journal Discussion HIV M184I 53 58 RT 59 62 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Also, virion-associated RT containing these two mutations had a significant decrease in RT processivity in comparison to WT, K65R and L74V RTs. 2011 Virology journal Discussion HIV K65R;L74V 125;134 129;138 RT;RT;RT 24;88;139 26;90;142 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Another study focusing on the selection parameters for L74V versus L74I mutations showed that the selection of the latter is more frequent under zidovudine and abacavir combination or under tenofovir with the presence of TAMs. 2011 Virology journal Discussion HIV L74I;L74V 67;55 71;59 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Biochemical analysis revealed that doubly mutant RT has a significant decreased ability to incorporate natural dNTPs in comparison to wild type RT and K65R RT. 2011 Virology journal Discussion HIV K65R 151 155 RT;RT;RT 49;144;156 51;146;158 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Considering the low level selection of K65R mutation in treatment-experienced patients exposed to abacavir or didanosine, which also select L74V, and the observations that patients with K65R experienced significantly higher rates of virologic suppression than did those with L74V requires further virological and biochemical investigation to understand the interactions among RT residues at codon 65 and 74 including impact of amino acid polymorphism. 2011 Virology journal Discussion HIV K65R;K65R;L74V;L74V 39;186;140;275 43;190;144;279 RT 376 378 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Evidently, the side chain of isoleucine improved the processivity of K65R+L74I RT during incorporation of 'T' nucleotide (alpha-32P TTP) rather than imparting a more severe structure-function constraint compared to K65R+L74V RT. 2011 Virology journal Discussion HIV K65R;K65R;L74I;L74V 69;215;74;220 73;219;78;224 RT;RT 79;225 81;227 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. For example, in contrast to the severe replication defect conferred by L74V mutation in the background of K65R, RT mutation A62V and S68G have been shown to improve replication capacity of virus when selected in the same genome that contain K65R mutation. 2011 Virology journal Discussion HIV A62V;K65R;K65R;L74V;S68G 124;106;241;71;133 128;110;245;75;137 RT 112 114 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In conjunction with improved replication kinetics of K65R+L74I viruses, RT containing K65R+L74I showed a significant increase in in vitro processivity in comparison to K65R+L74V RT. 2011 Virology journal Discussion HIV K65R;K65R;K65R;L74I;L74I;L74V 53;86;168;58;91;173 57;90;172;62;95;177 RT;RT 72;178 74;180 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In contrast to this the major influence observed with K65R+L74V RT may be during reinitiation and not during processive synthesis. 2011 Virology journal Discussion HIV K65R;L74V 54;59 58;63 RT 64 66 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In contrast, our analysis show that L I change at RT codon 74 improves RCs of viruses in the background of K65R, suggesting that the specific interaction among amino acid residues at RT codon 65 and 74 could have a different structural constraint. 2011 Virology journal Discussion HIV K65R 107 111 RT;RT 50;183 52;185 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In contrast, the selection of L74V is mainly associated with the use of didanosine. 2011 Virology journal Discussion HIV L74V 30 34 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In contrast, we show here that the K65R+L74I viruses replicated much more efficiently in PBM cells than those containing K65R+L74V. 2011 Virology journal Discussion HIV K65R;K65R;L74I;L74V 35;121;40;126 39;125;44;130 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In fact in MT-2 cells, viruses containing K65R+L74I mutations showed a better replication capacity, suggesting the role of higher dNTP concentrations of MT-2 cells in conferring an increased replication of mutant viruses. 2011 Virology journal Discussion HIV K65R;L74I 42;47 46;51 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In parallel to improved replication capacity of K65R+L74I viruses, our reversion assays showed a significant decrease in R K reversion at codon 65 in K65R+L74I viruses in comparison to those containing K65R+L74V mutation (Figure 4). 2011 Virology journal Discussion HIV K65R;K65R;K65R;L74I;L74I;L74V 48;150;202;53;155;207 52;154;206;57;159;211 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. In the context of L74I selection, a recent survey of large database revealed that TAMs and M184V are the most commonly observed nucleoside analogue mutations (>25%) followed by L74V/I (11%) and K65R remain stable (3.3%) between 2003-2006. 2011 Virology journal Discussion HIV K65R;L74I;L74I;L74V;M184V 194;177;18;177;91 198;183;22;183;96 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. It is conceivable that the robust RCs of L74I viruses will have an implication in the selection and prevalence of mutant viruses with L74I mutation presumably with thymidine analogue mutations under specific combination of drugs. 2011 Virology journal Discussion HIV L74I;L74I 41;134 45;138 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Other studies have demonstrated that the RT mutation M184V further decreases replication capacity of K65R viruses by decreasing the ability to incorporate natural dNTPs. 2011 Virology journal Discussion HIV K65R;M184V 101;53 105;58 RT 41 43 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Our data suggest that the side chain (methyl group) in isoleucine (74I) conferred a decreased structural constraint on RT to improve the replication of viruses containing K65R+L74I mutations. 2011 Virology journal Discussion HIV K65R;L74I 171;176 175;180 RT 119 121 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Our observations that L I but not L V change at RT codon 74 in the background of K65R leads to the generation of RT which is much more stable and enough for the enhanced viability of the virus (Figure 1 and Figure 4) is intriguing and needs to be addressed further. 2011 Virology journal Discussion HIV K65R 81 85 RT;RT 48;113 50;115 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Previous mutagenic study of RT codon 74 demonstrated that apart from L74M, other changes L74A, L74G, L74D did not yield enough RT to yield a viable virus. 2011 Virology journal Discussion HIV L74A;L74D;L74G;L74M 89;101;95;69 93;105;99;73 RT;RT 28;127 30;129 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Similar to L74V, the selection of L74I is also rare in the same HIV-1 genome that contains K65R mutation. 2011 Virology journal Discussion HIV K65R;L74I;L74V 91;34;11 95;38;15 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Since 74I possesses an additional side chain as a methyl group in comparison to 74V, we expected a more pronounced processivity defect with the RTs containing both mutations K65R+L74I in the same genome. 2011 Virology journal Discussion HIV K65R;L74I 174;179 178;183 RT 144 147 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. Specifically, the impact of emerging L74I in combination of other NRTI-selected mutations should be analyzed. 2011 Virology journal Discussion HIV L74I 37 41 NRTI 66 70 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. The significant linkage studies by Parikh et al (2006) had previously demonstrated that while TAMs are rarely observed in combination with K65R their association with L74V/I is more frequent. 2011 Virology journal Discussion HIV K65R;L74I;L74V 139;167;167 143;173;173 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. They further showed that K103N is also associated with L74I emergence in the absence of other NNRTI mutations (L100I, G190A and Y181C). 2011 Virology journal Discussion HIV G190A;K103N;L100I;L74I;Y181C 118;25;111;55;128 123;30;116;59;133 NNRTI 94 99 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. This study showed that the selection of L74V and L74I is controlled by two independent pathways and it is speculated that the resistance levels and replication capacity of viruses containing these mutations may be different. 2011 Virology journal Discussion HIV L74I;L74V 49;40 53;44 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We have shown previously that K65R and L74V mutations are incompatible and a 65R K reversion occurs during the replication of double mutant virus K65R+L74V. 2011 Virology journal Discussion HIV K65R;K65R;L74V;L74V 30;146;39;151 34;150;43;155 21255423 A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus. We speculate that a decreased R K reversion in K65R+L74I viruses is due to a decreased survival pressure as compared to the viruses with lethal combination K65R+L74V. 2011 Virology journal Discussion HIV K65R;K65R;L74I;L74V 47;156;52;161 51;160;56;165 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Compared to WT virus, CD4 loss and bystander apoptosis were both compromised in the V38E mutant. 2011 Virology journal Discussion HIV V38E 84 88 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Correlation analysis revealed that while in WT infection CD8 immune activation correlates with CD4 decline this was not true for V38E infection. 2011 Virology journal Discussion HIV V38E 129 133 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Given that the point mutation in gp41 restricts the cell-to-cell fusion capacity of the V38E mutant, while maintaining the virus-cell fusion activity and consequently virus replication, we can state that HIV Env mediated apoptosis is at least in part dependent on Env fusion function. 2011 Virology journal Discussion HIV V38E 88 92 gp41;Env;Env 33;208;264 37;211;267 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Hence it is not surprising that immune activation was seen with the V38E virus as it replicated to similar levels as WT virus. 2011 Virology journal Discussion HIV V38E 68 72 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Incidentally, the V38E mutant is one of the Enfuvirtide resistant mutation associated with immunological benefits in patients undergoing Enfuvirtide therapy. 2011 Virology journal Discussion HIV V38E 18 22 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Interestingly immune activation between V38E and WT virus infection was similar even though CD4 decline was limited in V38E infection. 2011 Virology journal Discussion HIV V38E;V38E 40;119 44;123 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. Our in vitro data in this study using WT or V38E infected Sup-T1 cells confirms this hypothesis. 2011 Virology journal Discussion HIV V38E 44 48 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. The differential loss of CD4 cells mediated by WT and V38E virus in the presence of similar levels of viremia is a strong indicator of the role of gp41 in CD4 loss. 2011 Virology journal Discussion HIV V38E 54 58 gp41 147 151 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. The fact that in our study WT virus infection induces extensive bystander apoptosis that is strikingly absent in V38E virus infection is evidence that the fusogenic activity of the Env glycoprotein may play a key role in bystander apoptosis and consequently CD4 decline in vivo. 2011 Virology journal Discussion HIV V38E 113 117 Env 181 184 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. We find that V38E mutant is incapable of inducing bystander apoptosis in the presence of significant infection and replication in SupT1 cell line. 2011 Virology journal Discussion HIV V38E 13 17 21255440 Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice. While the use of a laboratory adapted X4 (Lai) isolate is also a limitation of our study the major emphasis of our study is on using the Lai WT and V38E mutant as a model system to study the phenomenon of bystander apoptosis. 2011 Virology journal Discussion HIV V38E 148 152 21276267 Interplay between HIV entry and transportin-SR2 dependency. Altered requirements of VSV-G pseudotyped HIV-1 Q63A/Q67A, E45A and N74D CA mutants for certain Nups, compared to wild type virus, were indeed demonstrated. 2011 Retrovirology Discussion HIV E45A;N74D;Q67A;Q63A 59;68;53;48 63;72;57;52 Capsid 73 75 21276267 Interplay between HIV entry and transportin-SR2 dependency. However, after pseudotyping the N74D CA mutant with envelopes derived from MLVampho (Figure 6B) or measles virus (Figure 6C) or in the presence of the wild type HIV-1 envelope (Figures 3C, D, 5C, D and 6A), the N74D CA mutant was intermediately impaired by TRN-SR2 knockdown. 2011 Retrovirology Discussion HIV N74D;N74D 32;211 36;215 Env;Env;Capsid;Capsid 52;167;37;216 61;175;39;218 21276267 Interplay between HIV entry and transportin-SR2 dependency. Hypothetically, the N74D mutant CA could direct PICs to an alternative transport pathway and a different compartment of the nuclear membrane where an unknown alternative import pathway is used. 2011 Retrovirology Discussion HIV N74D 20 24 Capsid 32 34 21276267 Interplay between HIV entry and transportin-SR2 dependency. If the N74D mutation alters the selection of the specific Nup, alternative importins may be chosen for nuclear import, which could also explain the reduced TRN-SR2 dependency of the N74D CA mutant when carrying the HIV-1 envelope. 2011 Retrovirology Discussion HIV N74D;N74D 7;182 11;186 Env;Capsid 221;187 229;189 21276267 Interplay between HIV entry and transportin-SR2 dependency. In a multiple round infection experiment using HeLaP4 cells stably depleted of TRN-SR2, which more closely resembles a natural occurring HIV infection than single round infection assays, the N74D CA mutant virus proved to be still dependent on TRN-SR2 (Figure 4D), although to a somewhat lesser extent than wild type HIV-1. 2011 Retrovirology Discussion HIV N74D 191 195 Capsid 196 198 HIV infections 137 150 21276267 Interplay between HIV entry and transportin-SR2 dependency. In an elegant study, Lee and colleagues describe how an HIV-1 CA mutant, N74D, renders HIV-1 resistant to a block in replication imposed by the ectopic expression of a C-terminally truncated version of CPSF6. 2011 Retrovirology Discussion HIV N74D 73 77 Capsid 62 64 21276267 Interplay between HIV entry and transportin-SR2 dependency. Intriguingly, the partial dependence on TRN-SR2 suggests that the N74D CA mutant is able to use an alternative nuclear import pathway besides TRN-SR2-mediated nuclear trafficking, especially when entering the cell via pH-dependent endocytosis. 2011 Retrovirology Discussion HIV N74D 66 70 Capsid 71 73 21276267 Interplay between HIV entry and transportin-SR2 dependency. It is plausible that the N74D CA mutation could inhibit or stimulate certain interactions of the incoming viral cores with cellular cofactors or restriction factors, thereby altering the structure of the PIC and shielding the interaction with TRN-SR2. 2011 Retrovirology Discussion HIV N74D 25 29 Capsid 30 32 21276267 Interplay between HIV entry and transportin-SR2 dependency. Overall, the N74D CA mutant is more infectious than the wild type virus in our hands, especially when pseudotyped with the VSV-G envelope, and this higher infectivity seems more pronounced in single round infection assays using bioluminescence to measure infectivity. 2011 Retrovirology Discussion HIV N74D 13 17 Env;Capsid 129;18 137;20 21276267 Interplay between HIV entry and transportin-SR2 dependency. This could explain why the N74D mutant loses its dependency on TRN-SR2 in particular when combined with a VSV-G envelope. 2011 Retrovirology Discussion HIV N74D 27 31 Env 112 120 21276267 Interplay between HIV entry and transportin-SR2 dependency. This may also explain the reduced TRN-SR2 dependency of the N74D CA mutant when carrying the HIV-1 envelope. 2011 Retrovirology Discussion HIV N74D 60 64 Env;Capsid 99;65 107;67 21276267 Interplay between HIV entry and transportin-SR2 dependency. VSV-G pseudotyping did not alter the requirement of wild type HIV-1 for TRN-SR2, although a single mutation in the CA protein (N74D) abolished the TRN-SR2 dependency of VSV-G pseudotyped HIV-1. 2011 Retrovirology Discussion HIV N74D 127 131 Capsid 115 117 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Following M184V, the model of reversion divides in two branches, one consisting of M41L, T215Y and L210W (branch 1) and the other branch consisting of K103N, K219Q and other RT mutations (branch 2). 2011 PloS one Discussion HIV K103N;K219Q;L210W;M184V;M41L;T215Y 151;158;99;10;83;89 156;163;104;15;87;94 RT 174 176 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. In branch 1, M41L, T215Y and L210W have been shown to preferably cluster together rather than with other members of the thymidine analog resistance mutation (TAM) pathway and to have a large impact on viral fitness. 2011 PloS one Discussion HIV L210W;M41L;T215Y 29;13;19 34;17;24 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Moreover, there is no evidence that M184V co- reverts with any particular RT resistance mutation. 2011 PloS one Discussion HIV M184V 36 41 RT 74 76 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Our analyses suggested that the rank of M184V in the model may be explained by its high prevalence and the large increase in viral RC associated with its reversion. 2011 PloS one Discussion HIV M184V 40 45 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Reversion of M184V was associated with large increases in viral RC, but RC alone cannot explain that M184V reverts first, since other secondary mutations were also associated with large RC changes. 2011 PloS one Discussion HIV M184V;M184V 13;101 18;106 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. The mutagenesis tree models showed that M184V, when present, was overall the first mutation to revert among all the RT mutations reported in this study. 2011 PloS one Discussion HIV M184V 40 45 RT 116 118 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. These patients showed faster rate of reversion of RT resistance mutations during the STI compared to the subset used in our analyses (although only Y181C and G190A were significantly faster, data not shown), and a higher median RC after 2 months STI (p = 0.002), suggesting the effect of other immunological and clinical factors on viral rebound. 2011 PloS one Discussion HIV G190A;Y181C 158;148 163;153 RT 50 52 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. This is most likely due to mutation linkage, since K103N had high co-reversion frequency with other mutations such as M184V and L100I. 2011 PloS one Discussion HIV K103N;L100I;M184V 51;128;118 56;133;123 21297946 Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. Using mutagenetic tree models, we found that in this dataset, M184V was the most prevalent mutation and the first to change, followed by the M41L, T215Y pathway or the K103N, K219Q pathway. 2011 PloS one Discussion HIV K103N;K219Q;M184V;M41L;T215Y 168;175;62;141;147 173;180;67;145;152 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? In this article we provide insights into a possibility how to maintain efficient selection pressure on the protease mutation at position L76V by combining one drug, which selects L76V (in this case LPV, APV, DRV) and another drug which gains efficiency when L76V develops. 2011 AIDS research and therapy Discussion HIV L76V;L76V;L76V 137;179;258 141;183;262 PR 107 115 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? This article reports about a significant clinical benefit of the protease mutation L76V on drug susceptibility to ATV and SQV due to resensitizing effects in multi-resistant patients resulting in a significantly higher long-term therapy success. 2011 AIDS research and therapy Discussion HIV L76V 83 87 PR 65 73 21314993 The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? who found that in the presence of the L76V substitution, ATV reveals a more productive binding affinity, in agreement with hypersusceptibily data. 2011 AIDS research and therapy Discussion HIV L76V 38 42 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Although S40F does not appear to affect the folding of the mature p6 protein, we can not exclude that this mutation indeed affect the overall structure of the PR55 polyprotein, which in turn would reduce the processing efficiency, a phenotype we clearly observed for the S40F mutant as a novel function of p6. 2011 Retrovirology Discussion HIV S40F;S40F 9;271 13;275 Gag;Gag;PR 66;306;159 68;308;161 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. In consistency, structural calculations indicated that the non-conservative exchange of Ser-40 to Phe does not change the ability of the molecule to adopt a helical structure. 2011 Retrovirology Discussion HIV S40F 88 101 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. In fact, the C-terminal alpha-helix is conserved in the S40F mutant, as it was established by NMR studies of the C-terminal peptides sp623-52. 2011 Retrovirology Discussion HIV S40F 56 60 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. In the case of Ser-40, this can be excluded, as the mutant S40F exhibits wt budding. 2011 Retrovirology Discussion HIV S40F 59 63 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Interestingly, the effect of the S40F mutation appears to be specific for the CA-SP1 cleavage inasmuch as i) no other Gag processing deficiency could be detected (Figure 6) and ii) enhancing CA processing by introducing the A1V mutation could restore the deficient core formation, and, consequently, enhance infectivity. 2011 Retrovirology Discussion HIV A1V;S40F 224;33 227;37 SP1;Gag;Capsid;Capsid 81;118;78;191 84;121;80;193 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Notably, virus release kinetic was not reduced for the S40F mutant providing first evidence that the L-domain function of p6 is not affected by mutation of Ser-40. 2011 Retrovirology Discussion HIV S40F 55 59 Gag 122 124 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. Our NMR experiments demonstrated that the C-terminal structure of p6 is not influenced by the S40F mutation. 2011 Retrovirology Discussion HIV S40F 94 98 Gag 66 68 21324168 Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. This was supported further by the observation that the ability of ALIX to rescue HIV-1DeltaPTAP L-domain mutant viruses was not influenced by the S40F mutation. 2011 Retrovirology Discussion HIV S40F 146 150 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. Although detection of this mutation in a virus from a single patient must be interpreted with caution, this finding suggests that the P145S mutation can be selected in vivo by raltegravir. 2011 AIDS (London, England) Discussion HIV P145S 134 139 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. It has been shown that the N155H mutation impairs viral replication capacity compared to wild type. 2011 AIDS (London, England) Discussion HIV N155H 27 32 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. The N155H mutation, which is associated in vitro with a modest decrease in raltegravir sensitivity, emerged in two patients. 2011 AIDS (London, England) Discussion HIV N155H 4 9 21326075 Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. We also found the unexpected emergence of the P145S mutation, which confers elvitegravir resistance but has not been associated with resistance to raltegravir. 2011 AIDS (London, England) Discussion HIV P145S 46 51 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. A clear example is the considerably reduced impact of mutating the 99% conserved R106 to lysine instead of the multiply defective R106A or fully defective R106L. 2011 Journal of neuroimmune pharmacology Discussion HIV R106A;R106L 130;155 135;160 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. Conversely, the multiply defective phenotype of the conservative mutation D123E is strongly suggestive of a unique role for D123 in Nef function. 2011 Journal of neuroimmune pharmacology Discussion HIV D123E 74 79 Nef 132 135 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. For example, P72A and P75A are less disruptive than the standard double mutation, AXXA for MHCI downregulation. 2011 Journal of neuroimmune pharmacology Discussion HIV P72A;P75A 13;22 17;26 21336563 Mechanisms of HIV-1 Nef function and intracellular signaling. The lack of a definitive phenotype for R106K leaves unexplained the fact that lysine is essentially excluded at Nef position 106. 2011 Journal of neuroimmune pharmacology Discussion HIV R106K 39 44 Nef 112 115 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. In this patient, the N348I connection domain mutation was selected by ZDV and/or didanosine therapy and confers resistance to ZDV, didanosine, NVP, EFV, delavirdine, tenofovir and etravirine. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N348I 21 26 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. N348I was probably not identified in our study because efavirenz, not NVP, was the NNRTI used for initial randomized therapy in ACTG A5142 and virologic failure was detected early using a sensitive definition of failure. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N348I 0 5 NNRTI 83 88 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. Other known polymerase domain mutations were not significantly associated with failure although, there were possible trends for K65R (p=0.13) and V106I/M (p=0.13). 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;V106I;V106M 128;146;146 132;153;153 Pol 12 22 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. The only mutations that were significantly more frequent at virologic failure than pre-therapy were K103N (p=0.001) and M184I/V (p=0.016) in the polymerase domain, which confer resistance to the study drugs EFV and 3TC, respectively. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;M184I;M184V 100;120;120 105;127;127 Pol 145 155 21350368 Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase. These studies have identified a number of mutations in the C-terminus of RT that are more frequent in ART-experienced patients compared to ART-naive including E312Q, G333D/E, G335C/D, N348I, R356K, R358K, A360I/V, A365I, T369I, A371V, A376S and K451R. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A360I;A360V;A365I;A371V;A376S;E312Q;G333D;G333E;G335C;G335D;K451R;N348I;R356K;R358K;T369I 205;205;214;228;235;159;166;166;175;175;245;184;191;198;221 212;212;219;233;240;164;173;173;182;182;250;189;196;203;226 RT 73 75 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. A simian-human immunodeficiency virus selected in macaques for resistance to PSC-RANTES, a CCR5 inhibitor based on one of its chemokine ligands, also contains a combination of V3 (K315R) and gp41 (N640D) changes. 2011 Virology Discussion HIV K315R;N640D 180;197 185;202 gp41 191 195 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Although derived from a common parent, CC1/85, two resistant viruses that we previously described, CC101.19 and D1/85.16, followed different genetic pathways to reach the same phenotypic endpoint: CC101.19 acquired four substitutions (K305R, H308P, A316V and G321E) in the V3 region, while the key determinants of resistance in D1/85.16 were three changes in the gp41 FP (G516V, M518V and F519I). 2011 Virology Discussion HIV A316V;F519I;G321E;G516V;H308P;K305R;M518V 249;389;259;372;242;235;379 254;394;264;377;247;240;384 gp41 363 367 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. An N406K substitution that results in the deletion of a potential N-linked glycosylation site was present in the gp120 V4 region in more than half of the D101.12 clones (8/13), including clone R14 as previously described. 2011 Virology Discussion HIV N406K 3 8 gp120 113 118 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Approximately half of the D101.12 clones (5/13) contained all four V3 changes, the rest possessing fewer, with only H308P being invariably present. 2011 Virology Discussion HIV H308P 116 121 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. As with the Pattern-I changes, the resistance-conferring effect of the Pattern-II substitutions was only manifested in the context of a virus containing the H308P substitution in V3, although the overall effect was to confer partial and not full resistance. 2011 Virology Discussion HIV H308P 157 162 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. By comparing the properties of various gp41 mutant clones of both sequence patterns that either contained or lacked the H308P change in V3, we found that the IC50 reductions are attributable to FP changes while the reduced MPI values are driven by the H308P substitution. 2011 Virology Discussion HIV H308P;H308P 120;252 125;257 gp41 39 43 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. For some resistant viruses from the D101.12 lineage, the use of VCV-CCR5 complexes may be facilitated by substitutions in gp41 that work in concert with at least the H308P change in V3. 2011 Virology Discussion HIV H308P 166 171 gp41 122 126 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Hence the V535M + G514V substitutions are necessary, but not sufficient, to cause VCV resistance, while neither change has much, if any effect, when made in isolation. 2011 Virology Discussion HIV G514V;V535M 18;10 23;15 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Hence we used the R14 clone, which contains only the H308P change in V3 and yet is fully VCV-resistant, in our domain swapping and mutagenesis strategies. 2011 Virology Discussion HIV H308P 53 58 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. In the alternative, more frequently seen and less complex, pathway, multiple changes in V3 achieve the same effect (i.e., for the fully resistant CC101.19 virus, H308P is supplemented by the three additional V3 changes). 2011 Virology Discussion HIV H308P 162 167 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Indeed, in a virus lacking the H308P change, the Pattern-II changes had less of an effect than Pattern I. 2011 Virology Discussion HIV H308P 31 36 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Inspection of the location of the N406K change on the gp120 core structure does not reveal any clues as to how it might affect the co-receptor interactions of the native Env trimer (data not shown). 2011 Virology Discussion HIV N406K 34 39 gp120;Env 54;170 59;173 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Other changes in V4, D407G and the loss of a glycosylation site at residue 386, have been reported to modulate the magnitude of clinical resistance to MVC that is conferred principally by V3 changes (Tilton et al.). 2011 Virology Discussion HIV D407G 21 26 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Resistance to a novel entry inhibitor, PF-68742, is associated with a G514R change in the FP, together with additional changes in gp41 that probably affect how this subunit interacts with gp120 (Murray et al.). 2011 Virology Discussion HIV G514R 70 75 gp120;gp41 188;130 193;134 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The D101.12 isolate arose from the weakly resistant CC101.6 virus that harbors the critical H308P change and, like D1/85.16, it is completely resistant to VCV in PBMC assays. 2011 Virology Discussion HIV H308P 92 97 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The FP residue involved is the same one that changes in the VCV escape mutants of gp41 Pattern-I, although the substitution associated with PF-68742 resistance involves the introduction of a positively charged residue (G514R vs. 2011 Virology Discussion HIV G514R 219 225 gp41 82 86 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The fully resistant D101.12 clone R14 contains an H308P substitution in V3 that confers modest VCV resistance, but lacks the three later-arising, resistance-associated changes in V3 that are often needed for full resistance. 2011 Virology Discussion HIV H308P 50 55 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The gp41 Pattern I changes were G514V + V535M, while Pattern II was M518V + F519L + V535M. 2011 Virology Discussion HIV F519L;G514V;M518V;V535M;V535M 76;32;68;40;84 81;37;73;45;89 gp41 4 8 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The gp41 sequence variations were accompanied by a minimum of one (H308P), but up to all four, of the resistance-associated substitutions in V3. 2011 Virology Discussion HIV H308P 67 72 gp41 4 8 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The increased T20 sensitivity of viruses bearing the gp41 Pattern-I sequence combination compared to other viruses from this lineage, irrespective of the presence or absence of the H308P change in gp120, provides clues to how these gp41 changes may be acting. 2011 Virology Discussion HIV H308P 181 186 gp120;gp41;gp41 197;53;232 202;57;236 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The R14/S+(G514V, V535M) mutant that recapitulates the R14 phenotype also has a comparable w value. 2011 Virology Discussion HIV G514V;V535M 11;18 16;23 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The two Pattern-I gp41 changes conferred full resistance when they were both present in a virus that also contained the H308P substitution in V3 (e.g., as in clone R14), but when H308P was absent they created only a partially resistant virus. 2011 Virology Discussion HIV H308P;H308P 120;179 125;184 gp41 18 22 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The two Pattern-II changes, M518V + F519L in the FP, did not confer resistance when introduced into a virus lacking the H308P change, and the further introduction of the V535M change to create the triple mutant produced only a weakly resistant virus. 2011 Virology Discussion HIV F519L;H308P;M518V;V535M 36;120;28;170 41;125;33;175 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The two separate gp41 sequence patterns both involved the substitution of hydrophobic amino acids in the FP (G514V, M518V, F519L), together with an additional V535M change. 2011 Virology Discussion HIV F519L;G514V;M518V;V535M 123;109;116;159 128;114;121;164 gp41 17 21 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. The V535M substitution appears to compensate for the otherwise replication impairing effect that is created when the G514V and H308P changes are combined, rather than having a direct impact on resistance. 2011 Virology Discussion HIV G514V;H308P;V535M 117;127;4 122;132;9 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. Thus, unlike in PBMC, the V535M change is not required to compensate for the presence of the H308P and G514V changes when the relevant viruses replicate in TZM-bl cells. 2011 Virology Discussion HIV G514V;H308P;V535M 103;93;26 108;98;31 21356539 Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41. We did not, however, further study the N406K change here, because it was not consistently present in all the D101.12 clones and it was not associated with the number or identity of the changes in V3 (data not shown). 2011 Virology Discussion HIV N406K 39 44 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. A follow-up genotypic analysis on the detection of K65R mutation in breast milk is necessary. 2011 PLoS medicine Discussion HIV K65R 51 55 21468304 HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. The appearance of K65R in one-quarter of the infants with resistance (Table 3) is of concern, and this might be due to a high level of 3TC in the breast milk. 2011 PLoS medicine Discussion HIV K65R 18 22 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. Five infants had other NVP resistance mutations detected at 14 weeks of age in the absence of K103N or Y181C (V106A, Y188C/L and G190A). 2011 AIDS (London, England) Discussion HIV G190A;K103N;V106A;Y181C;Y188C;Y188L 129;94;110;103;117;117 134;99;115;108;124;124 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. However, a previous study suggests that some of those mutations (V106M, Y188C, G190A) may be less likely to persist at high levels in infants after NVP exposure than K103N and Y181C. 2011 AIDS (London, England) Discussion HIV G190A;K103N;V106M;Y181C;Y188C 79;166;65;176;72 84;171;70;181;77 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. The frequent persistence of the K103N and Y181C mutations in infants after exposure to extended NVP prophylaxis prior to HIV diagnosis, with or without concomitant ZDV, suggests that exposure to these regimens may compromise an infant's subsequent response to an NNRTI-based treatment regimen, even if treatment initiation is delayed until 6-12 months of age. 2011 AIDS (London, England) Discussion HIV K103N;Y181C 32;42 37;47 NNRTI 263 268 21487249 Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis. The NVP resistance mutations, K103 and Y181C, were still detectable in 82.6% of evaluable infants at 6 months of age and in 65.5% of evaluable infants at 12 months of age. 2011 AIDS (London, England) Discussion HIV Y181C 39 44 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. Although subtype C isolates have been reported to have a higher tendency to develop K65R, in contrast we observed a lower rate of K65R (3%) compared with global reports. 2011 International health Discussion HIV K65R;K65R 84;130 88;134 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. Among the low genetic barrier NNRTI mutations, Y181C was the predominant mutation, followed by K103N, which is similar to what has been reported previously both in India and globally. 2011 International health Discussion HIV K103N;Y181C 95;47 100;52 NNRTI 30 35 21516199 Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India. Not surprisingly, M184V was the predominant mutation in this sample and its prevalence was comparable with that described for HIV patients failing HAART in other settings. 2011 International health Discussion HIV M184V 18 23 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Based on the VSV-G rescue experiments we hypothesized that the post-entry defects seen with R515A might be mediated by interaction of the tail of uncleaved Env with Gag as the interaction of the HIV gp41 cytoplasmic tail with Gag has been implicated in post-entry defects in certain Gag and Env mutants . 2011 Virology Discussion HIV R515A 92 97 gp41;Env;Env;Gag;Gag;Gag 199;156;291;165;226;283 203;159;294;168;229;286 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. For one, the Y164A mutant is not only restricted in budding by itself but also inhibits release of WT HIV Gag, suggesting a DN effect at this step. 2011 Virology Discussion HIV Y164A 13 18 Gag 106 109 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Interestingly, we also found that R515A was not only defective by itself but also inhibited WT virion infection at 1:1 ratio, indicating a DN phenomenon. 2011 Virology Discussion HIV R515A 34 39 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Mammano et al described the Q155N and Y164A CA mutations and their DN effect while studying the role of major homology region (MHR) of HIV Gag. 2011 Virology Discussion HIV Q155N;Y164A 28;38 33;43 Gag;Capsid 139;44 142;46 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. Our data show that CA mutants are more potent inhibitors of WT virus than MA mutants as evident from the enhanced inhibitory activity of Q155N and Y164A over 1GA. 2011 Virology Discussion HIV Q155N;Y164A 137;147 142;152 Matrix;Capsid 74;19 76;21 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. R515A is defective in the cleavage site between gp120 and gp41 and hence produces an uncleaved gp160 precursor protein which is obviously defective in fusion. 2011 Virology Discussion HIV R515A 0 5 gp120;gp160;gp41 48;95;58 53;100;62 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. That these virions were defective in a post-entry event was further suggested by the VSV-G rescue experiments, in which WT+Y164A virions could not be rescued for infection even after pseudotyping with VSV-G. 2011 Virology Discussion HIV Y164A 123 128 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. The Env mutants that have been studied for HIV inhibition include R515A and V513E (41.2). 2011 Virology Discussion HIV R515A;V513E 66;76 71;81 Env 4 7 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. These data suggest that Y164A not only inhibits release but also infectivity of WT virions. 2011 Virology Discussion HIV Y164A 24 29 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. This was supported by our observation that deletion of the gp41 cytoplasmic tail in context of the HIV R515A mutant (CTDel/R515A) resulted in a better recovery of virus infectivity with VSV-G pseudotyping as well as reduced dominant negative effects. 2011 Virology Discussion HIV R515A;R515A 103;123 108;128 gp41 59 63 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. V513E on the other hand has a substitution in the gp41 fusion peptide resulting in loss of fusion activity. 2011 Virology Discussion HIV V513E 0 5 gp41 50 54 21529874 Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy. We chose to study R515A in greater detail because of the lack of processing of gp160 to gp120 and gp41 would minimize soluble gp120 shedding from transduced/infected cells and limit any toxic side effects mediated by circulating gp120. 2011 Virology Discussion HIV R515A 18 23 gp120;gp120;gp120;gp160;gp41 88;126;229;79;98 93;131;234;84;102 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. A refined analysis of the emergence and development of these mutations in sequential samples by SGS revealed a chronological increase in frequency that paralleled the sequential acquisition of Q151M MDR mutations. 2011 Retrovirology Discussion HIV Q151M 193 198 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. As described earlier, N348I confers drug resistance by decreasing RNase H activity, thus it will be interesting to explore if a negative correlation exists between reduced RNase H activity and Q151M. 2011 Retrovirology Discussion HIV N348I;Q151M 22;193 27;198 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. In addition, the analysis showed genetic linkage of most of these mutations to Q151M MDR mutations indicating an association between the two. 2011 Retrovirology Discussion HIV Q151M 79 84 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. In this study, we took advantage of treatment failure in the absence of viral load-guided therapy to dissect the relative contribution of RT domains in the route to high-level NRTI drug resistance through the Q151M pathway. 2011 Retrovirology Discussion HIV Q151M 209 214 NRTI;RT 176;138 180;140 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. It was surprising to observe that the patient-derived connection subdomain and RNase H domain were not associated with the decreased susceptibility to NRTIs exhibited by the Q151M MDR-containing RTs and also that the N348I mutation disappeared prior to the acquisition of Q151M. 2011 Retrovirology Discussion HIV N348I;Q151M;Q151M 217;174;272 222;179;277 NRTI;RT 151;195 156;198 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. It will be interesting to elucidate the particular mutations involved and the mechanism behind the connection subdomain's effect on replicative fitness of the Q151M-containing RT. 2011 Retrovirology Discussion HIV Q151M 159 164 RT 176 178 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Of note, the intermediate Q151K or L mutations which have been postulated to be involved in the emergence of the Q151M mutation were never identified in our SGS analysis. 2011 Retrovirology Discussion HIV Q151K;Q151M 26;113 31;118 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. Our findings confirm previous reports showing that the Q151M-containing virus replicates poorly. 2011 Retrovirology Discussion HIV Q151M 55 60 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The database sequence analysis also showed that the DNA pol domain mutations at codon positions 31, 33, 48, 102, 123, 135, 174, 197 and 203 were significantly associated with Q151M in subtype B and/or C. 2011 Retrovirology Discussion HIV Q151M 175 180 Pol 56 59 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. The mutation at connection subdomain codon positions 386 and 403 were significantly associated with Q151M in the subtype B database analysis; however, a similar analysis could not be carried out for subtype C due to lack of samples sequenced beyond the DNA pol domain. 2011 Retrovirology Discussion HIV Q151M 100 105 Pol 257 260 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. This possibility could not be explored further in this study as we were unable to amplify any genomes at 28 months, the time point prior to the emergence of the Q151M mutation. 2011 Retrovirology Discussion HIV Q151M 161 166 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. This raises the possibility of suboptimal use of the drugs contributing to the emergence of the Q151M MDR complex. 2011 Retrovirology Discussion HIV Q151M 96 101 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. We clearly show that the patient-derived connection subdomain is important for improving the Q151M-containing virus' replicative fitness and is thus important for the development of the Q151M pathway. 2011 Retrovirology Discussion HIV Q151M;Q151M 93;186 98;191 21569325 The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. We show that although the connection subdomain mutations were acquired in parallel with Q151M MDR mutations they were not directly associated with drug resistance but played a role in improving the replicative fitness of the Q151M-containing viruses. 2011 Retrovirology Discussion HIV Q151M;Q151M 88;225 93;230 21569500 Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1. Eighty-three miRNA were downregulated and ablation of the HIV-1 Tat RNA silencing suppressor (K51A) lessened the downregulation of twenty-two miRNA (p = <=0.0001) (Table 5). 2011 Retrovirology Discussion HIV K51A 94 98 Tat 64 67 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Despite an increase in surface expression in the Y712C-containing mutants, there was a progressive decrease in Env fusogenicity from WT through C, after which Env fusogenicity stabilized (summarized in Table 1). 2011 Retrovirology Discussion HIV Y712C 49 54 Env;Env 111;159 114;162 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. The Y712 motif, however, appears to be important for regulating the cell surface expression of the HIV-1 Env, as evidenced by a minimum 4-fold increase in surface expression of the Y (Y712C) mutant. 2011 Retrovirology Discussion HIV Y712C 184 189 Env 105 108 21569545 Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. Three of these motifs (Y768XXL, L774LLI, and L784L) maintain the hydrophobicity of the Env CD, specifically in the LLP2 region, which is critically important for replication in T-cells. 2011 Retrovirology Discussion HIV L784L 45 50 Env 87 90 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Although the D30N has been identified as having an effect in vitro in HIV-1 clade C strains, it not known if the in vivo result is generalizable to other non-B clades and HIV-2. 2010 The open medical informatics journal Discussion HIV D30N 13 17 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. HIV variants with both the D30N and N88D mutation was also found to have decreased replication capacity in vitro, including subtype C strains. 2010 The open medical informatics journal Discussion HIV D30N;N88D 27;36 31;40 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. However, comparison is difficult due to the presence of different mutations in the HIV protease (D30N versus I54V+V82A), as well as the variability inherent in experiments employing SCID-hu mice in which a chimeric organ is created by engraftment of primary human tissues. 2010 The open medical informatics journal Discussion HIV D30N;I54V;V82A 97;109;114 102;113;118 PR 87 95 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. In addition, the M184V did not enhance or inhibit viral replication or the ability of the virus to deplete thymocytes when coupled with the D30N mutation. 2010 The open medical informatics journal Discussion HIV D30N;M184V 140;17 144;22 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. In people infected with clade B strains of HIV, those that harbor virus containing the D30N mutation often also have the L63P mutation. 2010 The open medical informatics journal Discussion HIV D30N;L63P 87;121 91;125 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. It is also possible that the D30N mutation might not be preferentially selected through nelfinavir treatment in non clade-B strains. 2010 The open medical informatics journal Discussion HIV D30N 29 33 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. It is noteworthy that previous studies have shown that the V28A and the D30N mutations do no co-occur in the same genome. 2010 The open medical informatics journal Discussion HIV D30N;V28A 72;59 76;63 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Moreover, others have reported that the replication of a D30N containing variant was not significantly different from a L63P+D30N dual mutant. 2010 The open medical informatics journal Discussion HIV D30N;D30N;L63P 57;125;120 61;129;124 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. N88D/S did not have a significant effect on fitness in the statistical model and was not tested. 2010 The open medical informatics journal Discussion HIV N88D;N88S 0;0 6;6 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Nonetheless, the differences in these results may also suggest that virus containing the D30N mutation is less able to replicate in the thymus than virus containing the V82A mutation (as is suggested by our bioinformatics model). 2010 The open medical informatics journal Discussion HIV D30N;V82A 89;169 93;173 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Once the D30N mutation has been acquired, the virus may not be able to replicate well enough to return to wild-type fitness. 2010 The open medical informatics journal Discussion HIV D30N 9 13 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Our results indicate that the D30N mutation has a substantial effect on the ability of HIV-1 to deplete thymocytes and to replicate in an in vivo system. 2010 The open medical informatics journal Discussion HIV D30N 30 34 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Similarly, patients with the D30N mutation often develop the N88D/S mutation. 2010 The open medical informatics journal Discussion HIV D30N;N88D;N88S 29;61;61 33;67;67 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The D30N mutation was chosen as it had the largest decrease in relative replication capacity. 2010 The open medical informatics journal Discussion HIV D30N 4 8 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. The L63P mutation was not identified as having a large fitness defect by our model, likely because the L63P mutation is prevalent in patients who are treatment naive and is therefore not a drug-resistance mutation. 2010 The open medical informatics journal Discussion HIV L63P;L63P 4;103 8;107 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. There was no statistically significant difference between mice infected with the D30N mutant and those infected with the D30N+M184V double mutant at any time point. 2010 The open medical informatics journal Discussion HIV D30N;D30N;M184V 81;121;126 85;125;131 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. This work was prefaced by a thorough examination of protease mutations in a bioinformatics system whereby the D30N mutation was found to have a profound effect on in vitro replication. 2010 The open medical informatics journal Discussion HIV D30N 110 114 PR 52 60 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. Whereas the virus containing the M184V mutation alone conferred a RC defect in vitro, we did not find evidence for decreased pathogenicity of this virus in vivo. 2010 The open medical informatics journal Discussion HIV M184V 33 38 21603285 In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1. who found that mice infected with a virus (210P) containing protease mutation at I54V and V82A had a higher level of viremia than mice infected with wild-type virus. 2010 The open medical informatics journal Discussion HIV I54V;V82A 81;90 85;94 PR 60 68 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Although with both Y181C and K103N the prevalence of mutations declined with age, the steepness of the decline was more marked with K103N. 2011 AIDS (London, England) Discussion HIV K103N;K103N;Y181C 29;132;19 34;137;24 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Analysis of the samples using both conventional genotyping and the more sensitive AS-PCR allowed us to detect interesting differences between the dynamics of Y181C and K103N mutations in children. 2011 AIDS (London, England) Discussion HIV K103N;Y181C 168;158 173;163 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Consistent with other pediatric studies, the Y181C mutation was most frequently detected. 2011 AIDS (London, England) Discussion HIV Y181C 45 50 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Further clarification of the clinical consequence of minority variant detection of Y181C and K103N in children is warranted. 2011 AIDS (London, England) Discussion HIV K103N;Y181C 93;83 98;88 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. However, in some cases polymorphisms can be tolerated as evidenced by the K103R genotype which did not interfere with the K103N assay. 2011 AIDS (London, England) Discussion HIV K103N;K103R 122;74 127;79 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. In addition, 100% and 98% of the samples could be analyzed by the K103N and Y181C AS-PCR assays respectively. 2011 AIDS (London, England) Discussion HIV K103N;Y181C 66;76 71;81 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. In children, Y181C detected either by standard methods or using ultra-sensitive methods have been associated with attenuated virologic response to nevirapine-based therapy. 2011 AIDS (London, England) Discussion HIV Y181C 13 18 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. In more than two-thirds of cases, Y181C was detected by conventional genotyping with low level mutations detected by AS-PCR constituting the remainder. 2011 AIDS (London, England) Discussion HIV Y181C 34 39 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. In our study, analysis of the Y181C and K103N mutations by AS-PCR was sufficient, as other NNRTI mutations were rare as shown by population sequencing. 2011 AIDS (London, England) Discussion HIV K103N;Y181C 40;30 45;35 NNRTI 91 96 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Intriguing new results in adults suggests that Y181C when present only at low frequencies may not have as marked an adverse effect on response to efavirenz-based therapy. 2011 AIDS (London, England) Discussion HIV Y181C 47 52 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Only 5 samples (2%) were indeterminate on the Y181C assay, 2 of which were due to the presence of unusual amino acids within the primer binding region. 2011 AIDS (London, England) Discussion HIV Y181C 46 51 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. The presence of both Y181C and K103N in children may require longer periods before mutations fade sufficiently to allow for reintroducing NNRTI-based therapies. 2011 AIDS (London, England) Discussion HIV K103N;Y181C 31;21 36;26 NNRTI 138 143 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. This is in contrast to studies in women where K103N predominates. 2011 AIDS (London, England) Discussion HIV K103N 46 51 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Whereas with K103N the reverse pattern was observed, with more than 60% of mutations detected only with the more sensitive AS-PCR. 2011 AIDS (London, England) Discussion HIV K103N 13 18 21633285 HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. Y181C therefore appears to be a more persisting mutation in children compared to adults. 2011 AIDS (London, England) Discussion HIV Y181C 0 5 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. 9, start of NVP-containing treatment at month 6), resistant virus harbouring the Y181C mutation re-emerged under ART. 2011 PloS one Discussion HIV Y181C 81 86 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. Furthermore, 3 women (10%, all subtype D) exhibited proportions of resistant HIV-1 higher than 10% (K103N: 11%, K103N: 100%, Y181C: 100%) at month 6. 2011 PloS one Discussion HIV K103N;K103N;Y181C 100;112;125 105;117;130 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. However, 12 months after starting ART the majority of the viral population carried the Y181C mutation. 2011 PloS one Discussion HIV Y181C 87 92 21655245 Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. In this woman infected with HIV-1-subtype C, drug-resistant virus was detectable early after NVP-SD intake (Y181C: 16% at week 2), disappeared and was still undetectable 9 months after the initiation of ART. 2011 PloS one Discussion HIV Y181C 108 113 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Although RNA secondary structure may not directly influence K65R development in regard to subtypes B and C, a role for such secondary structure cannot be excluded for other subtypes and CRFs that share less sequence homology or that contain more polymorphisms. 2011 PloS one Discussion HIV K65R 60 64 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Another interesting consideration is whether the development of K65R-containing minority species may be enhanced during the acute phase of HIV-1 infection, and how this may influence transmitted drug resistance, since a large proportion of onward HIV-1 transmission occurs during this period. 2011 PloS one Discussion HIV K65R 64 68 HIV infections 139 154 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Another study used high-fidelity DNA polymerase and sensitive real-time PCR assays in treatment-naive individuals infected with subtype C HIV-1 and found that 6% of women and 15% of infants harbored K65R sequences as well as -1 frameshift mutants in which deletions of the A at the middle position of codon K65 were also found. 2011 PloS one Discussion HIV K65R 199 203 Pol 37 47 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. As a result, it is unlikely that K65R was generated as a result of simple misincorporation; instead, dislocation with realignment would have been the most probable mechanism whereby these enzymes might introduce base substitution mutations responsible for K65R development at the end of the homopolymeric sequence. 2011 PloS one Discussion HIV K65R;K65R 33;256 37;260 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. As a result, the contribution of K65R-containing viruses that have resulted from the realigned dislocation reaction and that contain in-frame transcripts become more important in the clinical setting. 2011 PloS one Discussion HIV K65R 33 37 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. As the enzyme approaches the K65 site, it encounters a homopolymeric stretch of 6 T nt followed by a single C immediately adjacent to the site of K65R development. 2011 PloS one Discussion HIV K65R 146 150 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Dislocation occurs at the same strong pause site that is responsible for occurrence of K65R that immediately follows a homopolymeric stretch of nt. 2011 PloS one Discussion HIV K65R 87 91 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In addition, our data suggest that approximately half of the products obtained from the subtype C reactions contain full-length K65R-containing transcripts whereas the other half contain the -1 frameshft mutation. 2011 PloS one Discussion HIV K65R 128 132 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In conclusion, we have shown that template-specific dislocation mutagenesis is the mechanism whereby subtype C HIV-1 viruses preferentially develop the K65R mutation. 2011 PloS one Discussion HIV K65R 152 156 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In one of these studies, the authors showed by allele-specific PCR that K65R was present in 4 of 30 subtype C samples after treatment failure with N(t)RTIs but not in equivalent subtype B specimens. 2011 PloS one Discussion HIV K65R 72 76 NRTI 147 155 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. In subtype C, a strong pause site was observed at the exact nt position responsible for K65R development and may be the cause for facilitated K65R development in subtype C viruses. 2011 PloS one Discussion HIV K65R;K65R 88;142 92;146 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Introduction of two silent subtype C nt polymorphisms into a subtype B NL4-3 virus, such that the homopolymeric sequence ends at the K65 site, rendered the subtype B virus hypersusceptible to K65R development. 2011 PloS one Discussion HIV K65R 192 196 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Nevertheless, over half of patients who failed therapy with appearance of the K65R mutation were still able to achieve a sustainable virologic response when later treated with regimens containing zidovudine or tenofovir. 2011 PloS one Discussion HIV K65R 78 82 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Newly infected people all harbor K65R minority species that result from spontaneous mutagenesis, although some may also have acquired this mutation by sexual transmission or by exposure to contaminated blood products. 2011 PloS one Discussion HIV K65R 33 37 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. None of the infected infants had mothers whose viruses contained the K65R mutation, suggesting that the mutations had developed spontaneously. 2011 PloS one Discussion HIV K65R 69 73 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Our findings are consistent with recent work on the role of the specific subtype C coding region surrounding codon 65 in the generation of K65R-containing viral minority species. 2011 PloS one Discussion HIV K65R 139 143 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Our findings suggest that the homopolymeric stretch in the (-)ssDNA intermediate template of subtype C HIV-1 can be considered to be a "mutational hot-spot" associated with development of K65R drug resistance. 2011 PloS one Discussion HIV K65R 188 192 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Several recent reports have evaluated the presence of K65R in subtype C-infected individuals and have used appropriate measures to minimize the appearance of PCR-induced false-positive K65R-containing minority variants. 2011 PloS one Discussion HIV K65R;K65R 54;185 58;189 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Strong termination by RT during DNA synthesis at this location, followed by dislocation-mediated base substitution, are the likely events that explain the rapid appearance of K65R in subtype C HIV-1. 2011 PloS one Discussion HIV K65R 175 179 RT 22 24 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Studies to assess this are currently underway in our laboratory, although the relative scarcity of these subtypes and CRFs, and the fact that they may harbor nt polymorphisms that favor the development of TAMs that antagonize the development of K65R, may mitigate against development of K65R in such viruses. 2011 PloS one Discussion HIV K65R;K65R 245;287 249;291 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Subtype C-infected patients who harbor K65R minority species because of dislocation mutagenesis seem to be at higher risk for development of K65R drug resistance. 2011 PloS one Discussion HIV K65R;K65R 39;141 43;145 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. The single-base substitution in the context of subtype C HIV-1, following dislocation of the primer and template, is responsible for the AAG-to-AGG substitution, giving rise to the K65R drug resistance mutation. 2011 PloS one Discussion HIV K65R 181 185 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. These data, along with our evidence for sequence and subtype-specific dislocation, suggest that the HIV-1 subtype C virus has evolved to possess a "mutational hot-spot" at the site of K65R development that is not seen in subtype B. 2011 PloS one Discussion HIV K65R 184 188 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. This work showed that the errors that result in K65R generation are not limited to HIV-1 RT but occur as well with other high-fidelity polymerase enzymes used in ultra-deep pyrosequencing reactions. 2011 PloS one Discussion HIV K65R 48 52 Pol;RT 135;89 145;91 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. Two recent reports also suggest that low-level K65R containing variants are more frequent in subtype C- than B-infected patients. 2011 PloS one Discussion HIV K65R 47 51 21655292 A template-dependent dislocation mechanism potentiates K65R reverse transcriptase mutation development in subtype C variants of HIV-1. With subtype C templates, reaction products included either a -1 frameshift mutation that deleted the middle A at codon K65 or full-length K65R-containing products. 2011 PloS one Discussion HIV K65R 139 143 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. As seen in other studies, M184V and the NNRTI-associated mutations were most prevalent in our cohort. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 26 31 NNRTI 40 45 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. In a Malawi study where treatment failure was not determined virologically, but clinically or immunologically, 93% of participants with viremia (on stored samples) had NNRTI mutations, 81% had M184V, and 56% harbored at least one TAM along with M184V and NNRTI mutations. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V;M184V 193;245 198;250 NNRTI;NNRTI 168;255 173;260 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. In conclusion, this study confirms the risk of selection of NNRTI and M184V mutations in patients who received EFV and 3TC in first-line cART. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 70 75 NNRTI 60 65 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. N348I may emerge on NRTI or NNRTI exposure, both of our patients received EFV. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N348I 0 5 NNRTI;NRTI 28;20 33;24 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. The detection of N348I in patients with DRM resistance suggests that sequencing programs that include this portion of RT will be useful in deriving a comprehensive drug resistance evaluation. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N348I 17 22 RT 118 120 21694608 Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa. Two patients in our study developed the connection domain mutation N348I, identified previously as contributing to substantial increase in AZT resistance, including patients with non-subtype B infection. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N348I 67 72 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. A recent crystal structure study enabled to describe the interactions between HIV-1 integrase residue Tyr 143 and the methyloxadiazole group of raltegravir, which could explain the role of the Y143C/H/R mutations in the development of resistance to raltegravir. 2010 Infection and drug resistance Discussion HIV Y143C;Y143H;Y143R 193;193;193 202;202;202 IN 84 93 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Among raltegravir-resistant double mutants, the highest selective-advantage profile was seen with G140S + Q148H. 2010 Infection and drug resistance Discussion HIV G140S;Q148H 98;106 103;111 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. However, 39 (29%) of the patients in the raltegravir arm of the EASIER study displayed at least one episode of low-level viremia on treatment and significant integrase resistance-associated mutations were detected in three subject (7.7%), including N155H in two subjects and P145S in one subject. 2010 Infection and drug resistance Discussion HIV N155H;P145S 249;275 254;280 IN 158 167 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Indeed, the level of phenotypic resistance to raltegravir associated with N155H is always much lower than that associated with Q148 or Y143 mutation (>100 times higher). 2010 Infection and drug resistance Discussion HIV N155H 74 79 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Moreover, the characterization of the phenotypic evolution showed that a switch from N155H to Y143C/R was linked to an increase in resistance to raltegravir. 2010 Infection and drug resistance Discussion HIV N155H;Y143C;Y143R 85;94;94 90;101;101 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Most of these shifts in raltegravir-resistance profiles were characterized by the loss of variants containing N155H and the emergence of variants containing Q148R/H or, in a few cases, Y143C/R. 2010 Infection and drug resistance Discussion HIV N155H;Q148H;Q148R;Y143C;Y143R 110;157;157;185;185 115;164;164;192;192 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Of the 11 assessable patients who displayed a viral rebound on raltegravir-based therapy, virus with mutations known to confer raltegravir resistance was found in eight patients: N155H (n = 6); Q148H/K/R +- G140S (n = 2); Y143C (n = 1). 2010 Infection and drug resistance Discussion HIV G140S;N155H;Q148H;Q148K;Q148R;Y143C 207;179;194;194;194;222 212;184;203;203;203;227 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Phenotypic studies assessing viral replicative capacity and phenotypic resistance levels of raltegravir-resistant viruses showed that among single mutants, the N155H had the highest selective-advantage profile. 2010 Infection and drug resistance Discussion HIV N155H 160 165 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Several studies reported that these primary resistance mutations Y143C/R, Q148H/K/R, and N155H represent mutually exclusive and nonoverlapping genotypic resistance pathways. 2010 Infection and drug resistance Discussion HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 89;74;74;74;65;65 94;83;83;83;72;72 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. The secondary mutations G140A/S, E92Q, and T97A are preferentially linked to the Q148, N155, and Y143 genetic pathways, respectively. 2010 Infection and drug resistance Discussion HIV E92Q;G140A;G140S;T97A 33;24;24;43 37;31;31;47 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. This finding likely explains why N155H can be selected early in the course of raltegravir resistance evolution in vivo but is later replaced by genotypes of the Q148 pathway. 2010 Infection and drug resistance Discussion HIV N155H 33 38 21694899 Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy. Three major raltegravir resistance-associated mutations are characterized and frequently detected in vivo in case of virological failure on a raltegravir-containing regimen: Q148H/K/R, N155H, and Y143C/H. 2010 Infection and drug resistance Discussion HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H 185;174;174;174;196;196 190;183;183;183;203;203 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Even so, the effect of M184V/I on viral fitness in vivo is confounded by the effects of other SDRMs and demographic/risk factors that should be handled using a causal modeling approach. 2011 PloS one Discussion HIV M184I;M184V 23;23 30;30 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Furthermore, Paredes and colleagues have recently observed that in vivo fitness is reduced in viruses carrying the M184V mutation in the absence of lamivudine. 2011 PloS one Discussion HIV M184V 115 120 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. In contrast, the clinical consequences of D67N/G and K219Q/E are not as well known. 2011 PloS one Discussion HIV D67G;D67N;K219E;K219Q 42;42;53;53 48;48;60;60 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Mutations such as M184V may be transmitted less often due to the reduced overall viral load in those subjects, whereas mutations such as K103N may increase in prevalence. 2011 PloS one Discussion HIV K103N;M184V 137;18 142;23 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Of all position-specific effects of SDRMs on baseline prognostic markers inferred from these data, one of the largest and most statistically significant was M184V/I. 2011 PloS one Discussion HIV M184I;M184V 157;157 164;164 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. On the other hand, experimental studies of M184V/I-containing recombinant HIV-1 are potentially not subject to these confounding factors, and M184V has been reported to reduce fitness by as much as 16-fold in vitro . 2011 PloS one Discussion HIV M184I;M184V;M184V 43;43;142 50;50;147 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Our results give the first evidence that the transmission of D67N/G may have deleterious virological and immunological consequences in therapy-naive patients that may be compensated by K219Q/E. 2011 PloS one Discussion HIV D67G;D67N;K219E;K219Q 61;61;185;185 67;67;192;192 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Previous studies have also documented compensatory/epistatic interactions of other mutations acting on M184V/I, including K219Q and N384I. 2011 PloS one Discussion HIV K219Q;M184I;M184V;N384I 122;103;103;132 127;110;110;137 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Previous studies have reported no greater than a 3-fold reduction in pVL due to M184V/I, while M184I itself has been estimated to reduce fitness by 23% relative to M184V. 2011 PloS one Discussion HIV M184I;M184I;M184V;M184V 81;96;81;165 88;101;88;170 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Second, SDRMs that are slow to revert in the absence of selection (e.g., M41L, K103N, and T215X in RT and L90M in protease), implying a negligible cost to fitness, tend to have relatively high prevalence in therapy-naive sequences. 2011 PloS one Discussion HIV K103N;L90M;M41L;T215X 79;106;73;90 84;110;77;95 PR;RT 114;99 122;101 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Similarly, we have observed several compensatory interactions among mutations that would otherwise mask the actual effects of individual mutations on CD4 or pVL (e.g., D67N/G and K219Q/E). 2011 PloS one Discussion HIV D67G;D67N;K219E;K219Q 168;168;179;179 174;174;186;186 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. Taking such an approach, we have found that uncompensated M184V/I mutations are causally associated with a 50-fold reduction in baseline pVL in therapy-naive patients. 2011 PloS one Discussion HIV M184I;M184V 58;58 65;65 21701595 Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load. The effects of D67N/G and K219Q/E on CD4 in our study were mirrored by significant effects on pVL; i.e., substitutions at D67 were causally associated with a 2.5-fold increase in pVL that was only partially compensated by substitutions at K219. 2011 PloS one Discussion HIV D67G;D67N;K219E;K219Q 15;15;26;26 21;21;33;33 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. A third patient with a high frequency of K103N mutants was given a protease inhibitor in addition to efavirenz, and this could have contributed to the virological response. 2011 PloS one Discussion HIV K103N 41 46 PR 67 75 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Allele-specific real-time PCR detected K103N mutants in 9 more patients harboring a low frequency of mutated viruses than did direct sequencing. 2011 PloS one Discussion HIV K103N 39 44 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. But ultra-deep pyrosequencing was not as sensitive as allele-specific real-time PCR for detecting K103N mutants at very low frequency. 2011 PloS one Discussion HIV K103N 98 103 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. By contrast, the mutated virus populations of 4 of the 6 patients harboring 0.1-10% K103N mutants underwent further selection and treatment failed for 2 of these patients. 2011 PloS one Discussion HIV K103N 84 89 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. However, 2 of the patients who responded to cART had only a few K103N mutants. 2011 PloS one Discussion HIV K103N 64 69 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. In conclusion, we have found that allele-specific real-time PCR and ultra-deep pyrosequencing are more sensitive than direct sequencing for detecting K103N mutants in the particular setting of intermittent antiretroviral therapy, with an excellent correlation between both mehods for quantifying the mutated viruses. 2011 PloS one Discussion HIV K103N 150 155 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. Our assay on the GS Junior can detect K103N minor variants that account for 1.5% of total virus if the number of reads is above 2500. 2011 PloS one Discussion HIV K103N 38 43 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The 7 patients harboring <0.1% K103N mutants, as detected by allele-specific real-time PCR, experienced no further selection of their mutated viruses, or treatment failure. 2011 PloS one Discussion HIV K103N 31 36 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The fourth had under 3 log10 copies/mL of K103N mutants but nevertheless underwent further selection of the mutated virus population. 2011 PloS one Discussion HIV K103N 42 47 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The impact of emergent K103N mutations on the subsequent virological response to cART in the 8 patients harboring >0.1% of the K103N mutated viruses varied. 2011 PloS one Discussion HIV K103N;K103N 23;127 28;132 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The K103N mutants found in the patients who paradoxically responded to cART might have had altered replicative fitness. 2011 PloS one Discussion HIV K103N 4 9 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The last 2 patients had high frequencies of K103N mutants but paradoxically maintained a virological response on efavirenz-based regimen during the intermittent therapy scheme, and on continuous therapy with the same regimen upon completion of the study. 2011 PloS one Discussion HIV K103N 44 49 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. The threshold above which minor K103N mutants could lead to virological escape seemed to be 0.1-1%. 2011 PloS one Discussion HIV K103N 32 37 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. This may have occurred as the half-life of efavirenz was significantly higher in the 8 patients in whom K103N emerged than in the 11 patients in whom it did not. 2011 PloS one Discussion HIV K103N 104 109 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We assayed the pharmacokinetics of efavirenz to determine whether its variability could influence the emergence of the K103N mutation. 2011 PloS one Discussion HIV K103N 119 124 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We found that 3 of the 4 patients in whom drug-resistant viruses subsequently emerged had over 3 log10 copies/mL K103N mutants when first detected by allele-specific real-time PCR. 2011 PloS one Discussion HIV K103N 113 118 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We have assessed the performances of allele-specific real-time PCR and ultra-deep pyrosequencing for detecting minor K103N mutants in patients given efavirenz while on intermittent antiretroviral therapy. 2011 PloS one Discussion HIV K103N 117 122 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We have now retrospectively evaluated two ultrasensitive methods for detecting K103N mutants in this context at high risk for the emergence of resistance. 2011 PloS one Discussion HIV K103N 79 84 21738752 Minor HIV-1 variants with the K103N resistance mutation during intermittent efavirenz-containing antiretroviral therapy and virological failure. We used the upper 99% confidence limit of the error rate to calculate the frequency of artefactual sequences for a given number of reads and the Poisson distribution to estimate the number of reads above which K103N mutants found at low frequencies were authentic rather than artefactual. 2011 PloS one Discussion HIV K103N 210 215 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Different patterns could be observed for these mutants during treatment interruption: The M184V mutation was occasionally detected in two patients independent of its presence prior to early ART, which reflects probably sporadic and temporary appearance of this drug-resistant variant. 2011 PloS one Discussion HIV M184V 90 95 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Drug-related selection of K103N viruses is unlikely. 2011 PloS one Discussion HIV K103N 26 31 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Furthermore, the discriminatory ability of the K103N AS-PCR assay is 20-fold more sensitive than the M184V AS-PCR, therefore, sporadic appearance of K103N viruses would have been more easily detectable, which was not observed. 2011 PloS one Discussion HIV K103N;K103N;M184V 47;149;101 52;154;106 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Furthermore, the K103N mutation did not appear in any other of the five patients who switched from a ritonavir-boosted PI to efavirenz. 2011 PloS one Discussion HIV K103N 17 22 PI 119 121 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. However, selection of the M184V mutation during continuously fully suppressive ART in our patients is very unlikely. 2011 PloS one Discussion HIV M184V 26 31 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. If selection was the cause for the appearance of drug-resistant variants after treatment interruption, it would have been anticipated that the M184V mutation rather than the K103N mutation is predominantly selected, because all patients received lamivudine, which can rapidly select M184V viruses. 2011 PloS one Discussion HIV K103N;M184V;M184V 174;143;283 179;148;288 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. In one patient, minority K103N HIV-1 variants reappeared shortly after treatment interruption and persisted for more than 1.2 years in the absence of any selective pressure. 2011 PloS one Discussion HIV K103N 25 30 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. In summary, we observed that the K103N mutation can reappear and persist at low frequencies in the absence of selective pressure after treatment interruption when it was already present as minority drug-resistant HIV-1 variant during primary HIV-1 infection. 2011 PloS one Discussion HIV K103N 33 38 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. K103N viruses were able to reappear and persist. 2011 PloS one Discussion HIV K103N 0 5 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. On the contrary, the K103N mutation is not associated with a major impact on viral fitness. 2011 PloS one Discussion HIV K103N 21 26 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. On the contrary, the random and seldom appearance of the M184V mutation in these patients suggests that viral replication is very low or most likely even completely inhibited during ART. 2011 PloS one Discussion HIV M184V 57 62 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. On the other hand, the K103N mutation reappeared in two patients both harboring this minority variant prior to early ART. 2011 PloS one Discussion HIV K103N 23 28 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Reappearance and fluctuations of minority K103N and/or M184V HIV-1 variants was studied in patients initiating early ART during primary HIV-1 infection and undergoing intended treatment interruption of suppressive ART without any evidence for virological failure. 2011 PloS one Discussion HIV K103N;M184V 42;55 47;60 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. That the K103N mutation also sporadically appears can not be excluded, however, this probably occurs less frequently compared to the M184V mutation. 2011 PloS one Discussion HIV K103N;M184V 9;133 14;138 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. The M184V mutation does rather show sporadic appearance. 2011 PloS one Discussion HIV M184V 4 9 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. The presence of the M184V mutation alleviates virus fitness (reviewed in) and these viruses are rapidly replaced by M184 wild-type viruses in the absence of selective pressure, thus, transient emergence, i.e., appearance and rapid disappearance, of HIV-1 variants with reduced viral fitness is probable during the time period of treatment interruption. 2011 PloS one Discussion HIV M184V 20 25 21754996 Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. Thus, sporadic appearance of minority M184V HIV-1 variants could be demonstrated. 2011 PloS one Discussion HIV M184V 38 43 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Early escape clones (patients C and D) with lower resistance were outcompeted by more resistant clones carrying the V38A or N43D resistance mutations respectively, indicating that the level of resistance reached is indeed one major determinant of evolution, as previously suggested. 2011 PloS one Discussion HIV N43D;V38A 124;116 128;120 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. Furthermore, the HR1-HR2 recombinant viruses from this patient were less susceptible to enfuvirtide than the HR1-HR2 recombinants from the other patients despite the N42S polymorphism, which has been associated with increased enfuvirtide susceptibility and a slightly improved virological outcome. 2011 PloS one Discussion HIV N42S 166 170 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. one single mutation (V38A) was inserted by site-directed mutagenesis. 2011 PloS one Discussion HIV V38A;V38A 22;21 26;25 21760896 Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates. We found that both determinants within the HR1-HR2 regions (including compensatory mutations such as the S138A, N125D or N126K) and other gp120 properties likely accounted for gains in viral infectivity. 2011 PloS one Discussion HIV N125D;N126K;S138A 112;121;105 117;126;110 gp120 138 143 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. However, the clinical significance of M184V on later ART has not been evaluated. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 38 43 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. However, the pattern of resistance differed, with significantly greater selection of resistance to lamivudine (M184V) in women randomly assigned to NFV, and selection of nevirapine resistance (K103N, Y181C and/or G190A) in women randomized to NVP. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G190A;K103N;M184V;Y181C 213;193;111;200 218;198;116;205 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. low NFV trough concentrations plus low triphosphorylation of ZDV in cells would result in unopposed 3TC pressure and favor the selection of M184V). 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 140 145 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. Mutations encoding M184I/V have been reported across studies of pregnant and postpartum women. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 19;19 26;26 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The high rate of resistance in our study is consistent with rates reported in a larger observational study of NFV-ART, which detected M184V in 29% by consensus sequencing and 52% by allele-specific PCR. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 134 139 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The longer half-life of NVP compared to 3TC likely protected participants randomized to NVP-ART from selection of M184V. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 114 119 21765365 Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. The study population was small, and while a significant difference was detected in the selection of M184V, the small group sizes precluded an analysis of differences in the selection of resistance to other ARV. 2011 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 100 105 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. However, consistent with our results, Girouard and colleagues detected a 21.7-fold enzymatic resistance to 3TC-TP in RTs harboring just V118I. 2011 PloS one Discussion HIV V118I 136 141 RT 117 120 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. In addition, we also found that the mutation V118I was associated with enzymatic 3TC resistance in the absence of M184V in 3 of 4 cases. 2011 PloS one Discussion HIV M184V;V118I 114;45 119;50 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. In vitro, V118 is reported to confer resistance to 3TC and other nucleoside analogues only in combination with other mutations like D67N and T215Y. 2011 PloS one Discussion HIV D67N;T215Y 132;141 136;146 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. Our data also show that the screening Amp-RT format detecting resistance to NVP correlated with the presence of K103N, Y181C/I, Y188L, and G190A/Q. 2011 PloS one Discussion HIV G190A;G190Q;K103N;Y181C;Y181I;Y188L 139;139;112;119;119;128 146;146;117;126;126;133 RT 42 44 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. We demonstrate that enzymatic 3TC resistance was strongly associated with M184I/V. 2011 PloS one Discussion HIV M184I;M184V 74;74 81;81 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. We have found previously that this approach was feasible, given the high level of resistance conferred by M184V and many NNRTI mutations. 2011 PloS one Discussion HIV M184V 106 111 NNRTI 121 126 21799767 Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing. While K103N or Y188L confer high cross-resistance between NVP and EFV, Y181C/I/V is associated with only moderate resistance to EVF. 2011 PloS one Discussion HIV K103N;Y181C;Y181I;Y181V;Y188L 6;71;71;71;15 11;80;80;80;20 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. (66), in which HIV-1 carrying a Q91L mutation in the RT gene was found to be noninfectious and replication-incompetent. 2011 Biochemistry Discussion HIV Q91L 32 36 RT 53 55 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Although the conservative mutant derivative Q91N has an amide side chain like Q91, it is shorter and, as a result, does not form productive interaction with the side chain of Y183. 2011 Biochemistry Discussion HIV Q91N 44 48 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Double mutants Q91A/M184V and Q91N/M184V. 2011 Biochemistry Discussion HIV M184V;M184V;Q91A;Q91N 20;35;15;30 25;40;19;34 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Due to the lack of an amide side chain in Q91A, favorable electrostatic interactions do not takes place with the primer terminus and Y183 residue. 2011 Biochemistry Discussion HIV Q91A 42 46 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Enzyme fidelity, as studied by the polymerase reaction in the absence of one dNTP, suggests higher enzyme fidelity for Q91N substitution in relation to wild-type and both Q91A/M184V and Q91N/M184V mutant enzymes on DNA and RNA templates. 2011 Biochemistry Discussion HIV M184V;M184V;Q91A;Q91N;Q91N;M184V;M184V;Q91A;Q91N;Q91N 177;192;172;120;187;176;191;171;119;186 182;197;176;124;191;181;196;175;123;190 Pol 35 45 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. However, the E89G mutant enzyme has been shown to have higher processivity, which probably compensates for its decreased forward synthesis, a consequence of decreased polymerase activity and increased fidelity. 2011 Biochemistry Discussion HIV E89G 13 17 Pol 167 177 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. In general, Q91N enzyme presents a pattern of resistance to ddNTPs similar to that of the Y183F mutant enzyme. 2011 Biochemistry Discussion HIV Q91N;Y183F 12;90 16;95 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Interestingly, the results for mutant Q91N clearly suggest that this mutant behaves somewhat similarly to Y183F mutant derivative of HIV-1 RT. 2011 Biochemistry Discussion HIV Q91N;Y183F 38;106 42;111 RT 139 141 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Interestingly, the same authors readily isolated E89K as a PFA-resistant mutation from MT-2 cells exposed to increasing concentrations of the drug. 2011 Biochemistry Discussion HIV E89K 49 53 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. It has been reported that mutation E89G is resistant to PFA, along with ddTTP, ddCTP, ddATP, ddGTP, AZTTP, and 3TCTP. 2011 Biochemistry Discussion HIV E89G 35 39 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. It was expected that similar mutations at position 91 might also manifest enzyme characteristics similar to those observed for Y183F mutant. 2011 Biochemistry Discussion HIV Y183F 127 132 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Mutant enzymes Q91A, carrying a nonconservative substitution, and Q91N, with a conservative substitution, were studied. 2011 Biochemistry Discussion HIV Q91A;Q91N 15;66 19;70 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Q91A mutant enzyme was found to be more impaired in its polymerase activity than was the Q91N mutant enzyme. 2011 Biochemistry Discussion HIV Q91N;Q91A 89;0 93;4 Pol 56 66 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Q91N mutant derivative is characterized by increased resistance to ddNTP analogs and increased fidelity. 2011 Biochemistry Discussion HIV Q91N 0 4 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Restoration of the polymerase activity of Q91N/M184V double mutant to the level of wild-type polymerase activity can also be explained based on the closer proximity of Q91N side chain amide group to the Q161 side chain amide group compared to corresponding distance seen in Q91N single mutant (single mutant, Q91N amide ---Q161 amide 3.4 A versus double mutant, Q91N amide---Q161 amide, 3.0 A). 2011 Biochemistry Discussion HIV M184V;Q91N;Q91N;Q91N;Q91N;Q91N 47;42;168;274;309;362 52;46;172;278;313;366 Pol;Pol 19;93 29;103 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Since deleterious effect of Y183F mutation was reversed by introducing a second M184V mutation, we proposed to examine if similar reversal effect could be seen on Q91 mutants by introducing M V mutation at 184 position with wild type side chain at position 183. 2011 Biochemistry Discussion HIV M184V;Y183F 80;28 85;33 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The compensating effect was more pronounced when the 184 mutation was in the presence of the Q91N mutation. 2011 Biochemistry Discussion HIV Q91N 93 97 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The compensatory effect of the M184V mutation on the polymerase activities of both Q91A and Q91N mutant derivatives. 2011 Biochemistry Discussion HIV M184V;Q91A;Q91N 31;83;92 36;87;96 Pol 53 63 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The observation that Q91N also has more discriminatory ability is further supported by our results regarding use of rNTP against dNTP for all four mutant enzymes. 2011 Biochemistry Discussion HIV Q91N 21 25 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. The Q91N enzyme seems to be more resistant to ddNTPs than is Q91A/M184V and Q91N/M184V mutant enzymes as judged by gel extension assay and higher Ki and IC50 values for these analogs. 2011 Biochemistry Discussion HIV M184V;M184V;Q91A;Q91N;Q91N 66;81;61;4;76 71;86;65;8;80 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. Their attempts to recover infectious viruses containing mutation Q91L were not successful and they concluded that this mutation might not be viable. 2011 Biochemistry Discussion HIV Q91L 65 69 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. These enzyme characteristics are similar to those of the E89G mutant enzyme that has been isolated from HIV-1 infected cell culture. 2011 Biochemistry Discussion HIV E89G 57 61 HIV infections 104 118 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. To analyze the inter-residue and residue-primer interactions, we did mutant modeling of Q91A and Q91N, as well as double mutants Q91A/M184V and Q91N/M184V in the 3D crystal structure of the ternary complex. 2011 Biochemistry Discussion HIV M184V;M184V;Q91A;Q91A;Q91N;Q91N 134;149;88;129;97;144 139;154;92;133;101;148 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. To summarize, Q91N/M184V double mutant was found to be similar to the wild-type enzyme with respect to its ddNTP sensitivity, rNTP utilization and fidelity, whereas Q91A/M184V double mutant is much less efficient than the wild-type enzyme. 2011 Biochemistry Discussion HIV M184V;M184V;Q91A;Q91N 19;170;165;14 24;175;169;18 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. We have also noted that the Y183F mutant RT was severely impaired in its catalysis of pyrophosphorolysis on a DNA template. 2011 Biochemistry Discussion HIV Y183F 28 33 RT 41 43 21800837 The glutamine side chain at position 91 on the beta5a-beta5b loop of human immunodeficiency virus type 1 reverse transcriptase is required for stabilizing the dNTP binding pocket. While examining the inverse nature of interaction between AZT resistant and foscarnet (phosphonoformic acid, PFA)-resistant mutants in vivo, they intended to introduce PFA resistance, one involving residue 89 (E89K) into engineered AZT resistant background. 2011 Biochemistry Discussion HIV E89K 210 214 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. also investigated RAL resistance using 454 sequencing and reported detection of Y143H, Y143C, and Q148R prior to initiation of therapy. 2011 AIDS (London, England) Discussion HIV Q148R;Y143C;Y143H 98;87;80 103;92;85 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. One of the main questions in initiating this analysis was whether the first resistance mutation to arise, N155H, was present prior to initiating therapy. 2011 AIDS (London, England) Discussion HIV N155H 106 111 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Our findings taken together support the idea that Y143H, and possibly Y143C and Q148R, are authentic replication-competent polymorphisms that are present in viral populations in the absence of RAL. 2011 AIDS (London, England) Discussion HIV Q148R;Y143C;Y143H 80;70;50 85;75;55 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. Similarly for Q148H, the major form at the last time-point, only three reads were detected, a number also attributable to error. 2011 AIDS (London, England) Discussion HIV Q148H 14 19 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. The Y143C and Q148R substitutions were marginally significant by some measures but did not survive correction for multiple comparisons. 2011 AIDS (London, England) Discussion HIV Q148R;Y143C 14;4 19;9 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. This is consistent with the idea that viruses with N155H or Q148H substitutions are considerably less fit than wild-type and so are very low in abundance in the absence of pressure from RAL. 2011 AIDS (London, England) Discussion HIV N155H;Q148H 51;60 56;65 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. We analyzed the evolutionary dynamics of RAL DRMs for three patients who showed a switch from the N155H to the Q148H pathway. 2011 AIDS (London, England) Discussion HIV N155H;Q148H 98;111 103;116 21832937 Switching between raltegravir resistance pathways analyzed by deep sequencing. We did find significant enrichment for Y143H in one participant by all measures and possible enrichment in a second (marginally significant relative to HIVNL4-3 and significant relative to simulated data). 2011 AIDS (London, England) Discussion HIV Y143H 39 44 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. A whole-population study suggested a possible association of T97A with both N155H and Y143C mutations in resistant HIV-2 viruses. 2011 Retrovirology Discussion HIV N155H;T97A;Y143C 76;61;86 81;65;91 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. E92Q has been described as a primary resistance mutation for another INSTI, elvitegravir. 2011 Retrovirology Discussion HIV E92Q 0 4 INSTI 69 74 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. E92Q is considered to be a secondary mutation within the N155H and Y143C pathways for HIV-1 resistance to RAL. 2011 Retrovirology Discussion HIV N155H;Y143C;E92Q 57;67;0 62;72;4 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. For the G140S/Q148H pattern, Q148H caused a major catalytic defect while conferring a high level of resistance to RAL, the catalytic defect being rescued in vitro by the secondary G140S mutation, which did not itself confer resistance. 2011 Retrovirology Discussion HIV G140S;G140S;Q148H;Q148H 8;180;14;29 13;185;19;34 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. For the N155H mutation, the level of resistance conferred by single-site directed mutagenesis was very similar to that of the enzyme amplified from the E92A/T97A/N155H clinical isolate, suggesting that the E92A and T97A secondary mutations provided no additional resistance. 2011 Retrovirology Discussion HIV E92A;N155H;T97A;E92A;N155H;T97A 152;162;157;206;8;215 156;167;161;210;13;219 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. However, this effect was not confirmed in the HIV-2 context, because the E92Q mutation, introduced through single-site directed mutagenesis, did not significantly increase the resistance of the HIV-2 mutant IN in vitro. 2011 Retrovirology Discussion HIV E92Q 73 77 IN 207 209 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Indeed, E92Q confers resistance to HIV-1 IN in vitro, albeit to a lesser extent than N155H or Q148R. 2011 Retrovirology Discussion HIV E92Q;N155H;Q148R 8;85;94 12;90;99 IN 41 43 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. It has been suggested that the emergence of Y143C during HIV-1 infection may result from a late switch from the N155H pathway. 2011 Retrovirology Discussion HIV N155H;Y143C 112;44 117;49 HIV infections 57 72 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Moreover, a previous clonal analysis found that E92Q was associated with both the N155H and Y143C mutations, whereas T97A mutation was associated with Y143C. 2011 Retrovirology Discussion HIV E92Q;N155H;T97A;Y143C;Y143C 48;82;117;92;151 52;87;121;97;156 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Nonetheless, the Y143C/E92Q double mutation obtained by mutagenesis of the wild-type control resulted in resistance in vitro. 2011 Retrovirology Discussion HIV E92Q;Y143C 23;17 27;22 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Our clonal analysis based on seven clinical isolates identified three different patterns, E92A/T97A/N155H, G140S/Q148R and E92Q/143C, confirming the probable existence of these three pathways. 2011 Retrovirology Discussion HIV E92A;N155H;T97A;E92Q;G140S;Q148R 90;100;95;123;107;113 94;105;99;127;112;118 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Our data show that, in HIV-2 infection, the Y143C mutation counteracts the resistance conferred by the N155H mutation, probably precluding the simultaneous selection of both mutations. 2011 Retrovirology Discussion HIV N155H;Y143C 103;44 108;49 HIV infections 23 38 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Similarly, we observed no significant effect of T97A in combination with Y143C, on HIV-2 IN susceptibility to RAL. 2011 Retrovirology Discussion HIV T97A;Y143C 48;73 52;78 IN 89 91 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Surprisingly, we observed that, although the Y143C-containing HIV-2 IN was amplified from clinical isolate of a patient at time of RAL failure, Y143C mutation alone was not sufficient to confer resistance to IN in vitro, ruling out this mutation as a sole determinant of resistance in the HIV-2 context. 2011 Retrovirology Discussion HIV Y143C;Y143C 45;144 50;149 IN;IN 68;208 70;210 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The concomitant selection of the Q148H/R/K and G140S mutations in both HIV-1 and HIV-2 RAL-resistant viruses is grounded in the structure of IN, indicating a close interaction between these two residues that are conserved in retroviral IN. 2011 Retrovirology Discussion HIV G140S;Q148H;Q148K;Q148R 47;33;33;33 52;42;42;42 IN;IN 141;236 143;238 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The IN sequence amplified from the clinical isolate also contained the E92Q mutation. 2011 Retrovirology Discussion HIV E92Q 71 75 IN 4 6 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. The three IN sequences studied all displayed the N17G, R34K, I133V, R224Q, N270H, M287R and V292M variations, with respect to the EHO group B reference sequence, suggesting that these variations are prevalent and may even form a consensus in HIV-2 group B circulating strains. 2011 Retrovirology Discussion HIV I133V;M287R;N17G;N270H;R224Q;R34K;V292M 61;82;49;75;68;55;92 66;87;53;80;73;59;97 IN 10 12 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. This hypothesis is consistent with the absence of resistance observed for INs into which T97A and E92Q were introduced as single mutations. 2011 Retrovirology Discussion HIV E92Q;T97A 98;89 102;93 IN 74 77 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. This was not the case here, as the Y143C/E92Q recombinant enzyme was less resistant than the N155H-containing enzyme. 2011 Retrovirology Discussion HIV E92Q;N155H;Y143C 41;93;35 45;98;40 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Thus, although neither Y143C nor E92Q is sufficient for significant resistance to RAL, the presence of both these substitutions in the same protein leads to resistance indicating that unlike HIV-1, at least two mutations seem to be required in this pathway to elicit resistance in HIV-2. 2011 Retrovirology Discussion HIV E92Q;Y143C 33;23 37;28 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Thus, although we did not investigate the effect of E92 mutations on the in vitro resistance of N155H-containing HIV-2 IN, we suggest that the emergence of E92A/G/Q secondary mutations, facilitated by the single nucleotide change required for all substitutions -- E to A, E to G or E to Q transition -- may be involved in the switch from the N155H to the Y143C pathway in the HIV-2 context. 2011 Retrovirology Discussion HIV E92A;E92G;E92Q;N155H;N155H;Y143C 156;156;156;96;342;355 164;164;164;101;347;360 IN 119 121 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Thus, N155H is the main, if not only determinant of viral resistance in this pathway, consistent with the findings of previous phenotypic studies of viral replication. 2011 Retrovirology Discussion HIV N155H 6 11 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Under this hypothesis, Y143C-containing resistant viruses would be expected to be more resistant to RAL than N155H-containing viruses. 2011 Retrovirology Discussion HIV N155H;Y143C 109;23 114;28 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. We showed, by single-site mutagenesis in a RAL-susceptible background, that the N155H mutation and the G140S/Q148H double mutation were sufficient to elicit strong resistance to RAL in HIV-2 IN in vitro. 2011 Retrovirology Discussion HIV G140S;N155H;Q148H 103;80;109 108;85;114 IN 191 193 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. We therefore studied the impact of this mutation within the Y143C background. 2011 Retrovirology Discussion HIV Y143C 60 65 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Y143C/E92Q-containing INs from clinical isolates also harbored G27E, G70E, G82R and Q124R variants, which were not found in the HIV-2 group B RAL-susceptible sequences. 2011 Retrovirology Discussion HIV E92Q;G27E;G70E;G82R;Q124R;Y143C 6;63;69;75;84;0 10;67;73;79;89;5 IN 22 25 21854605 G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not. Y143C/R has been described as a primary mutation for HIV-1 resistance to RAL. 2011 Retrovirology Discussion HIV Y143C;Y143R 0;0 7;7 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. Another interesting aspect of our results is to establish that the single mutation A182T, which is located away from the dimerization interface, has a considerable impact on the CCD assembly although the tertiary structure of the fragment is preserved. 2011 PloS one Discussion HIV A182T 83 88 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. As an illustration, we produced and tried to crystallize the H103A mutant and the H103A/A182T double mutant of RAV-1 IN CCD using the "new" and the "canonical" crystallization conditions. 2011 PloS one Discussion HIV A182T;H103A;H103A 88;61;82 93;66;87 IN 117 119 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. No crystal was obtained with RAV-1 IN CCDH103A, and large crystals of RAV-1 IN CCDH103A/A182T were observed but with the "canonical" condition only. 2011 PloS one Discussion HIV A182T;H103A 88;82 93;87 IN;IN 35;76 37;78 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. Our first assumption was that our novel dimeric arrangement with its three pairs of facing alpha-helices at the interface (alpha3/alpha5, alpha1/alpha1 and alpha5/alpha3) was a crystallization artifact, but the formation of a covalently bonded dimer for the H103C mutant gave insight on the new dimeric assembly during bacterial production. 2011 PloS one Discussion HIV H103C 258 263 21857987 A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. These results, like those obtained with the the H103C mutant, suggest that both His103 and a bound Zn(II) are necessary to the creation of the new interface. 2011 PloS one Discussion HIV H103C 48 53 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Both proteases that were tested (HXB2 and PR-2) processed substrate with mutation A364V one order of magnitude more effectively than substrate with a V362I mutation. 2011 Retrovirology Discussion HIV A364V;V362I 82;150 87;155 PR;PR 5;42 14;44 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Furthermore, the relative increase in substrate conversion is greater in the context of the PR-2 protease compared to the HXB2 protease and we hypothesize that this relative increase in CA/p2 processing contributes to the enhanced bevirimat resistance levels observed for the PR-2GagV362I and PR-2GagS368N viruses. 2011 Retrovirology Discussion HIV S368N;V362I 300;283 305;288 PR;PR;Capsid;PR;PR;PR 97;127;186;92;276;293 105;135;188;94;278;295 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. High levels of bevirimat resistance for mutation V362I have also been observed in other genetic backgrounds. 2011 Retrovirology Discussion HIV V362I 49 54 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. In addition, we identified a previously unknown bevirimat resistance mutation, S368N. 2011 Retrovirology Discussion HIV S368N 79 84 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. Mutation A364V occurred most frequently and was associated with a completely resistant phenotype in all three protease backgrounds (HXB2, PR-1 and PR-2). 2011 Retrovirology Discussion HIV A364V 9 14 PR;PR;PR 110;138;147 118;140;149 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. This might explain the high levels of bevirimat resistance conferred by A364V in all backgrounds. 2011 Retrovirology Discussion HIV A364V 72 77 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. This mutation had no effect on replication in an HXB2 background, which might explain the almost exclusive selection of A364V by viruses with a wild-type protease. 2011 Retrovirology Discussion HIV A364V 120 125 PR 154 162 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. We also showed this to be the case for mutation V362I, which recently has been identified as a natural polymorphism that confers bevirimat resistance. 2011 Retrovirology Discussion HIV V362I 48 53 21864346 HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. When introduced into the PR-2 background, mutations V362I and S368N result in much higher levels of resistance than in backgrounds HXB2 or PR-1. 2011 Retrovirology Discussion HIV S368N;V362I 62;52 67;57 PR;PR 25;139 27;141 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. In fact, only one patient, subtype CRF02_AG, had L90M mutation probably as a result of receiving antiretroviral therapy during two years (1/28, 3.5%). 2011 Virology journal Discussion HIV L90M 49 53 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. It is of note that one treatment naive patient, with G subtype, showed major RT mutations associated with resistance to NRTI (K70R) and NNRTI (A98G). 2011 Virology journal Discussion HIV A98G;K70R 143;126 147;130 NNRTI;NRTI;RT 136;120;77 141;124;79 21871090 Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010. Our results indicated that patients infected with HIV-1 non-B subtypes showed a high frequency of minor PR mutations (polymorphisms) as M36I, L63P, and K20R/I, in contrast to the low proportion of major resistance mutations. 2011 Virology journal Discussion HIV K20I;K20R;L63P;M36I 152;152;142;136 158;158;146;140 PR 104 106 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Among the CA mutants tested, the N74D was the least dependent on Tnp3 for infection, suggesting that either the N74D CA was shed before nuclear entry or that it could exploit different factors for its export, becoming more promiscuous. 2011 PLoS pathogens Discussion HIV N74D;N74D 33;112 37;116 Capsid;Capsid 10;117 12;119 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. In pull down assays, we have detected binding of Tnp3 to the N74D CA mutant (Figure S5). 2011 PLoS pathogens Discussion HIV N74D 61 65 Capsid 66 68 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Interestingly, the A105S CA mutation made the virus insensitive to this block. 2011 PLoS pathogens Discussion HIV A105S 19 24 Capsid 25 27 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Moreover, the A105T mutation in CA was shown before to influence HIV-1 post-entry events in a cyclophilin A (CypA) dependent way. 2011 PLoS pathogens Discussion HIV A105T 14 19 Capsid 32 34 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The biological significance of this result is supported by experiments with the N74D CA mutant HIV-1 vector. 2011 PLoS pathogens Discussion HIV N74D 80 84 Capsid 85 87 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. The time course experiment shown in Figure 11 also suggested that N74D CA does not enter into the nucleus, at least for up to 24 h post-infection. 2011 PLoS pathogens Discussion HIV N74D 66 70 Capsid 71 73 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. Therefore it appears that the N74D CA is shed before nuclear entry of the RTC/PIC, making Tnp3 unnecessary. 2011 PLoS pathogens Discussion HIV N74D 30 34 Capsid 35 37 21901095 Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. We have also detected CA in the nuclei of control cells 16 h post-infection by immunofluorescence whereas mutant N74D CA localized mostly outside the nuclei or at the nuclear envelope (Figure S5). 2011 PLoS pathogens Discussion HIV N74D 113 117 Env;Capsid;Capsid 175;22;118 183;24;120 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. HIV resistance to tenofovir is conferred by a single codon mutation (K65R). 2012 Nucleic acids research Discussion HIV K65R 69 73 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. HIV-1 RTs containing the M41L, D67N, K70R, T215Y/F, K219E/Q mutations show enhanced removal of AZT. 2012 Nucleic acids research Discussion HIV D67N;K219E;K219Q;K70R;M41L;T215F;T215Y 31;52;52;37;25;43;43 35;59;59;41;29;50;50 RT 6 9 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. In HIV, decreased binding of AZT is conferred initially in the presence of the primary Q151M mutation, followed by secondary mutations F77L, A62V, V75I and F116Y. 2012 Nucleic acids research Discussion HIV A62V;F116Y;F77L;Q151M;V75I 141;156;135;87;147 145;161;139;92;151 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. In HIV, moderate resistance to EFdA is conferred by the emergence of the M184V mutation at the conserved X position of the conserved YXDD motif of the polymerase active site. 2012 Nucleic acids research Discussion HIV M184V 73 78 Pol 151 161 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. It may also contribute to the decreased ability of XMRV RT to unblock chain-terminated primers, as was also reported for M184V HIV-1 RT and to the enhanced fidelity reported here for XMRV RT, which is also reminiscent of the previously reported high fidelity of M184V HIV-1 RT. 2012 Nucleic acids research Discussion HIV M184V;M184V 121;262 126;267 RT;RT;RT;RT 56;133;188;274 58;135;190;276 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. K65R causes resistance to tenofovir by lowering the kpol for the incorporation of the inhibitor into the nascent DNA. 2012 Nucleic acids research Discussion HIV K65R 0 4 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. We demonstrated that introducing the primary Q M mutation at the equivalent XMRV RT site (Q190M) resulted in an enzyme with decreased susceptibility to AZT. 2012 Nucleic acids research Discussion HIV Q190M 90 95 RT 81 83 21908397 Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase. We prepared XMRV RT with the equivalent mutation, K103R, and determined that it has decreased susceptibility to tenofovir. 2012 Nucleic acids research Discussion HIV K103R 50 55 RT 17 19 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. A mutant alpha4beta7 carrying K201N/I/E, again alone or in combination with other alpha4beta7 polymorphisms, also showed reduced affinity to HIV-1 gp120 proteins of different subtypes. 2011 PloS one Discussion HIV K201E;K201I;K201N 30;30;30 39;39;39 gp120 147 152 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. In fact, the reduction of HIV-1 gp120 binding to alpha4beta7 harboring K201E/I/N, in which the substitution of a positively-charged amino acid for a neutral or even negatively charged residue occurs, can be mechanistically compared to the binding of gp120 to the coreceptors CCR5 or CXCR4 through its V3 loop. 2011 PloS one Discussion HIV K201E;K201I;K201N 71;71;71 80;80;80 gp120;gp120 32;250 37;255 21912696 Polymorphisms in the alpha4 integrin of neotropical primates: insights for binding of natural ligands and HIV-1 gp120 to the human alpha4beta7. This was the case of the K201N/I/E and K208E/G substitutions, found in many distinct genera of NWP. 2011 PloS one Discussion HIV K201E;K201I;K201N;K208E;K208G 25;25;25;39;39 34;34;34;46;46 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. 83% among published sequences), >=1 NRTI resistance mutations (11% vs 9%), the prevalence of K103N (55% vs 42%), M184V/I (66% vs. 2011 Journal of AIDS & clinical research Discussion HIV K103N;M184I;M184V 93;113;113 98;120;120 NRTI 36 40 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Although K103N and other NNRTI resistance mutations confer high level NNRTI resistance, six patients in our study who harbored such mutations, re-suppressed VL after 4 to 10 months with no change in their first-line regimen. 2011 Journal of AIDS & clinical research Discussion HIV K103N 9 14 NNRTI;NNRTI 25;70 30;75 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Among eight patients with TAMs, the most common pathway (seen in 6/8 patients) was TAM-2 related (D67N, K70R, K219Q/R/E); and the rest (2/8) were mixed with the TAM-1 pathway (M41L, L210W, T215Y) extending similar prior Southern African observations. 2011 Journal of AIDS & clinical research Discussion HIV D67N;K219E;K219Q;K219R;K70R;L210W;M41L;T215Y 98;110;110;110;104;182;176;189 102;119;119;119;108;187;180;194 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Surprisingly, a number of patients with DRM that predict high-level resistance, K103N with or without M184V, were successfully re-suppressed on the same first-line regimen. 2011 Journal of AIDS & clinical research Discussion HIV K103N;M184V 80;102 85;107 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. The majority (63%) had >=3 DRM, mostly including K103N accompanied by M184V/I, at times with complex mixtures of additional NRTI and NNRTI mutations. 2011 Journal of AIDS & clinical research Discussion HIV K103N;M184I;M184V 49;70;70 54;77;77 NNRTI;NRTI 133;124 138;128 21927716 Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa. Three of these patients had high level resistance to two drug classes, with the addition of the M184V mutation, conferring resistance to lamivudine. 2011 Journal of AIDS & clinical research Discussion HIV M184V 96 101 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Although the DNA prime/protein boost immunization with the N448Q mutant elicited comparable levels of gp120-binding and virus-neutralizing Ab titers as that with the wild type gp120, the mutant elicited higher levels of gp120-specific lymphoproliferation and secretion of Th2-associated cytokines. 2011 Vaccine Discussion HIV N448Q 59 64 gp120;gp120;gp120 102;176;220 107;181;225 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. By contrast, immune complexes made with N448Q or N448E were potent in eliciting higher titers of both neutralizing and non-neutralizing Abs than the wild type complex. 2011 Vaccine Discussion HIV N448E;N448Q 49;40 54;45 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Enhanced immunogenicity of the gp120 mutants was further demonstrated by the ability of the immune complexes made with N448Q or N448E gp120s to induce higher titers of binding and neutralizing Abs than the wild type complex. 2011 Vaccine Discussion HIV N448E;N448Q 128;119 133;124 gp120;gp120 31;134 36;140 21945958 Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune complex formation. Nevertheless, DNA prime/protein boost vaccination, even with the N448Q mutant displaying enhanced V3 reactivity, was not adequate for eliciting Abs against neutralizing V3 epitopes. 2011 Vaccine Discussion HIV N448Q 65 70 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. According to the WHO drug resistance algorithm, substitution D67E has the potential to cause low-level resistance to zidovudine, stavudine, and didanosine while D67G causes low-level resistance to zidovudine, and a potential for low-level resistance to abacavir, stavudine, and didanosine. 2011 Journal of health, population, and nutrition Discussion HIV D67E;D67G 61;161 65;165 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. In the same vein, T69D causes low-level resistance to didanosine, with a potential for low-level resistance to stavudine. 2011 Journal of health, population, and nutrition Discussion HIV T69D 18 22 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. Mutations in D67E, D67G, and T69D were detected in three women while T215Y and M46I were detected in two men. 2011 Journal of health, population, and nutrition Discussion HIV D67E;D67G;M46I;T215Y;T69D 13;19;79;69;29 17;23;83;74;33 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. Several polymorphisms, such as K20R, M36I, and I93L, common in HIV-1 subtype C viruses and associated with drug resistance site, were also observed as has been previously reported. 2011 Journal of health, population, and nutrition Discussion HIV I93L;K20R;M36I 47;31;37 51;35;41 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. Substitution T215Y causes intermediate resistance to zidovudine and stavudine and low-level resistance to abacavir, didanosine, and tenofovir. 2011 Journal of health, population, and nutrition Discussion HIV T215Y 13 18 21957668 Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among newly-diagnosed drug-naive persons visiting a voluntary testing and counselling centre in northeastern South Africa. The only protease inhibitor (PI) mutation observed :M46I:causes intermediate resistance to nelfinavir, with a potential for low-level resistance to ritonavir-boosted doses of atazanavir, fosamprenavir, indinavir, and lopinavir. 2011 Journal of health, population, and nutrition Discussion HIV M46I 52 56 PR;PI 9;29 17;31 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. 2) and that the Q148R and N155H changes individually confer moderate resistance to raltegravir in a single cycle of infection. 2011 AIDS (London, England) Discussion HIV N155H;Q148R 26;16 31;21 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. 3) and the sequence data currently available from HIV-2-infected patients, suggest that additional changes in HIV-2 integrase are required in combination with Y143C, Q148R or N155H to achieve high-level raltegravir resistance. 2011 AIDS (London, England) Discussion HIV N155H;Q148R;Y143C 175;166;159 180;171;164 IN 116 125 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Additional, head-to-head comparisons of the phenotypic effects of Y143C in HIV-1 and HIV-2 are needed to resolve this issue. 2011 AIDS (London, England) Discussion HIV Y143C 66 71 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Although we cannot exclude the possibility that additional changes in the HIV-2 integrase protein play a compensatory role, our data suggest that the Q148R and N155H replacements define mutually exclusive pathways to raltegravir resistance in HIV-2. 2011 AIDS (London, England) Discussion HIV N155H;Q148R 160;150 165;155 IN 80 89 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Cooperative effects were also observed between the E92Q and Y143C replacements in HIV-2 integrase; although these changes individually had no measurable effect on raltegravir sensitivity, the E92Q with Y143C enzyme was approximately 10-fold resistant to the inhibitor. 2011 AIDS (London, England) Discussion HIV E92Q;E92Q;Y143C;Y143C 51;192;60;202 55;196;65;207 IN 88 97 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Finally, we note that the combination of two 'primary' resistance changes in HIV-2 (Q148R with N155H) confers a dramatic loss of raltegravir sensitivity. 2011 AIDS (London, England) Discussion HIV N155H;Q148R 95;84 100;90 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. For the latter two variants, the levels of resistance observed in our single-cycle assays were on par with those reported for Q148R and N155H mutants of HIV-1. 2011 AIDS (London, England) Discussion HIV N155H;Q148R 136;126 141;131 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. found that Y143C conferred 16-fold resistance to raltegravir in the Phenosense HIV-1 single-cycle test. 2011 AIDS (London, England) Discussion HIV Y143C 11 16 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Generally, the amino acid changes that appear in conjunction with Q148H/K/R, N155H and Y143C/R augment the level of raltegravir resistance in HIV-1 and, in some cases, mitigate the fitness costs incurred by primary resistance-associated mutations. 2011 AIDS (London, England) Discussion HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143R 77;66;66;66;87;87 82;75;75;75;94;94 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. In addition, we show that the Y143C, Q148R and N155H replacements in HIV-2 ROD9 integrase compromise viral replication capacity. 2011 AIDS (London, England) Discussion HIV N155H;Q148R;Y143C 47;37;30 52;42;35 IN 80 89 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. In contrast, the Y143C replacement in HIV-2 integrase had little or no effect on raltegravir sensitivity. 2011 AIDS (London, England) Discussion HIV Y143C 17 22 IN 44 53 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. recently showed that the combination of G140S with Q148R confers a more than 100-fold loss of raltegravir sensitivity in cell-free assays with purified integrase proteins. 2011 AIDS (London, England) Discussion HIV G140S;Q148R 40;51 45;56 IN 152 161 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. reported that Y143C alone is sufficient for high-level raltegravir resistance in HIV-1, as measured in HeLa-P4 indicator cell assays (EC50 approximately 500-fold greater than wild-type). 2011 AIDS (London, England) Discussion HIV Y143C 14 19 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Studies of HIV-1 patients have identified three principal mutational patterns that emerge in response to raltegravir treatment: Q148H/K/R with or without G140S/A, N155H with or without E92Q and Y143C/R with or without T97A. 2011 AIDS (London, England) Discussion HIV E92Q;G140A;G140S;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143R 185;154;154;163;128;128;128;218;194;194 189;161;161;168;137;137;137;222;201;201 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. The relatively low level of viral infectivity observed in our experiments potentially explains why the combination of Q148R and N155H has not been observed in sequences from raltegravir-treated HIV-2 patients. 2011 AIDS (London, England) Discussion HIV N155H;Q148R 128;118 133;123 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. These data suggest that HIV-1 and HIV-2 might differ with regard to the role of Y143C in raltegravir resistance, although it should be noted that other studies of HIV-1 mutants using multicycle assays reported relatively modest effects for Y143C (i.e., three-fold to four-fold raltegravir resistance). 2011 AIDS (London, England) Discussion HIV Y143C;Y143C 80;240 85;245 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. These findings are comparable to the data obtained in a previous analysis of Q148H with N155H mutants of HIV-1. 2011 AIDS (London, England) Discussion HIV N155H;Q148H 88;77 93;82 21971360 Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. Thus, Q148R and N155H individually confer similar effects on raltegravir susceptibility in HIV-1 and HIV-2, despite the fact that these viruses differ at approximately one third of the 109 amino acid sites in the integrase catalytic core domain. 2011 AIDS (London, England) Discussion HIV N155H;Q148R 16;6 21;11 IN 213 222 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Because non-neutralizing antibodies can bind uncleaved envelope, we considered the more trivial explanation that the increased binding to the T569A mutant at least partially reflects binding to uncleaved, non-functional trimers. 2011 Virology Discussion HIV T569A 142 147 Env 55 63 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Differences in binding are also not due to differences in the amount of total or cleaved Env on the cell surface as the T569A variant had similar total Env and lower levels of cleaved Env compared to Q461e2. 2011 Virology Discussion HIV T569A 120 125 Env;Env;Env 89;152;184 92;155;187 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. For the I675 changes, in the presence of T569A, but not in its absence, there is both increased binding and enhanced susceptibility to b12 neutralization. 2011 Virology Discussion HIV T569A 41 46 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. However, in other cases, such as the subtype A, Q461e2 variant studied here, the T569A may increase b12 binding, but the second mutation at I675 is needed to render the envelope sensitive to b12 neutralization. 2011 Virology Discussion HIV T569A 81 86 Env 169 177 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. However, the findings that T569A can increase neutralization sensitivity support the model that this amino acid change may induce a conformational change that allows antibody access to key b12 binding residues, resulting in b12 binding to the membrane-associated form of the envelope protein. 2011 Virology Discussion HIV T569A 27 32 Env 275 283 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. In the study of Wu et al., it was not possible to discern the effects of this mutation on Env-b12 binding because only binding to monomeric gp120 was examined, which would not reflect conformational changes contributed by the T569A change in gp41. 2011 Virology Discussion HIV T569A 226 231 gp120;gp41;Env 140;242;90 145;246;93 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Rather, these data suggest that there is a conformational effect that results from the T569A amino acid change in the gp41 that leads to b12 binding to Env expressed on the cell surface. 2011 Virology Discussion HIV T569A 87 92 gp41;Env 118;152 122;155 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Studies of Wu et al, 2009, demonstrated that the T569A change, when introduced into a b12-resistant subtype B variant (CAAN5342.A2), enhanced neutralization sensitivity to b12 and other MAbs. 2011 Virology Discussion HIV T569A 49 54 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. The Thr to Ala at position 569 is sufficient to permit antibody binding to gp120, as evidenced by binding to the MAb b12. 2011 Virology Discussion HIV T569A 4 30 gp120 75 80 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. These data therefore suggest that these gp41 changes participate in a two step process to promote neutralization by b12 antibody - one, induced by the T569A change, is a conformational change that permits b12 access to key binding residues; another, which results from a I675A/T/V change only occurs in the context of the conformational change induced by the T569A change. 2011 Virology Discussion HIV I675A;I675T;I675V;T569A;T569A 271;271;271;151;359 280;280;280;156;364 gp41 40 44 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Thus, if the increased binding due to the T569A mutation was simply due to increased levels of uncleaved envelope, we would expect that there would be detectable b12 binding to all the Env proteins. 2011 Virology Discussion HIV T569A 42 47 Env;Env 105;185 113;188 22029936 The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Thus, the T569A change may impact b12 sensitivity in the absence of other changes in certain viral contexts, but not in others (e.g. 2011 Virology Discussion HIV T569A 10 15 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. 4) CA proteins, P147L and S149A CA form tubular assemblies that are very similar to the long tubes assembled by WT CA, although some subtle differences can be detected by TEM. 2011 Virology Discussion HIV P147L;S149A 16;26 21;31 Capsid;Capsid;Capsid 3;32;115 5;34;117 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. A similar defect was also observed with two severely defective N-terminal CA mutants (W23A and F40A). 2011 Virology Discussion HIV F40A;W23A 95;86 99;91 Capsid 74 76 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. A striking result of this work is the novel finding that despite the poor replication capacity of P147L and S149A, infectivity can be rescued in an efficient and specific manner by pseudotyping env- virions with VSV-G (Tables 1 and 2). 2011 Virology Discussion HIV P147L;S149A 98;108 103;113 Env 194 197 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Accordingly, we find that the noninfectious mutant I150A makes ~104 less viral DNA products than WT and no late products. 2011 Virology Discussion HIV I150A 51 56 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Additional studies on the structure of the P147L and S149A CA proteins should be invaluable for elucidating the ultrastructure of HIV-1 conical cores and its relation to CA function. 2011 Virology Discussion HIV P147L;S149A 43;53 48;58 Capsid;Capsid 59;170 61;172 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Alternatively, some other aspect of VSV-G-mediated entry, e.g., faster fusion kinetics with VSV-G than with HIV-1 Env, might result in bypass of the infectivity defect conferred by the P147L and P149A mutations. 2011 Virology Discussion HIV P147L;P149A 185;195 190;200 Env 114 117 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Analysis of mutant phenotypes shows that the mutants can be divided into three classes: (i) infectious virions (S146A, T148A); (ii) completely noninfectious virions with severe defects in viral morphology and function (Y145A, I150A, L151A); and (iii) virions with very low infectivity, having an attenuated phenotype (P147L, S149A) (Table 1). 2011 Virology Discussion HIV I150A;L151A;P147L;S146A;S149A;T148A;Y145A 226;233;318;112;325;119;219 231;238;323;117;330;124;224 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Core instability of S149A was also observed in studies on HIV-1 CA residues that are potential substrates for phosphorylation. 2011 Virology Discussion HIV S149A 20 25 Capsid 64 66 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. However, in agreement with the EM analysis, synthesis of viral DNA products by the P147L and S149A mutants is reduced by only 10-fold compared with WT and all of the expected DNA products are detected. 2011 Virology Discussion HIV P147L;S149A 83;93 88;98 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. However, two mutants (P147L and S149A), while poorly infectious, exhibit an attenuated phenotype, including rescue of infectivity by pseudotyping with VSV-G, modest ability to undergo reverse transcription, and assembly of cores with seemingly normal architecture. 2011 Virology Discussion HIV P147L;S149A 22;32 28;37 RT 184 205 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. In accord with the CA sedimentation data, we also find that P147L, S149A, and I150A are unable to saturate TRIMCyp in the assay for abrogation of host restriction. 2011 Virology Discussion HIV I150A;P147L;S149A 78;60;67 83;65;72 Capsid 19 21 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Indeed, point mutations that lead to abrogation or severe reduction of infectivity are often associated with formation of virion cores that are highly unstable: retention of CA in core fractions is negligible (Y145A, I150A, L151A) or only slightly higher than background (P147L, S149A), whereas ~40% of total CA in the sample is associated with WT, S146A, and T148A cores under our conditions. 2011 Virology Discussion HIV I150A;L151A;P147L;S146A;S149A;T148A;Y145A 217;224;272;349;279;360;210 222;229;277;354;284;365;215 Capsid;Capsid 174;309 176;311 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Moreover, in contrast to the Y145A. 2011 Virology Discussion HIV Y145A 29 34 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Moreover, of all the mutants studied here, Y145A is the only one that exhibits a CypA deficiency. 2011 Virology Discussion HIV Y145A 43 48 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Most likely, retention of the WT phenotype in the case of T148A (Table 1) is due to the conservative change from threonine to alanine. 2011 Virology Discussion HIV T148A 58 63 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Mutations in three of these residues (Y145A, I150A, and L151A) lead to a total loss of infectivity, defects in core morphology and stability, as well as virtually complete abrogation of viral DNA synthesis. 2011 Virology Discussion HIV I150A;L151A;Y145A 45;56;38 50;61;43 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Reduction of RT activity associated with unstable mutant cores is less severe than depletion of CA in the case of P147L and S149A. 2011 Virology Discussion HIV P147L;S149A 114;124 119;129 Capsid;RT 96;13 98;15 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Residue Y145 is crucial for formation of this interface and for biological function, since Y145A or Y145F mutants are not infectious and have defects in core stability and assembly, consistent with our Y145A data (Table 1; Figs. 2011 Virology Discussion HIV Y145A;Y145A;Y145F 91;202;100 96;207;105 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Similar results were obtained for S149A and S178A in one of the studies of CA phosphorylation. 2011 Virology Discussion HIV S149A;S178A 34;44 39;49 Capsid 75 77 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Taken together, our results raise the following question: "How can we reconcile our finding that in two assays affected by core stability, P147L and S149A give negative results. 2011 Virology Discussion HIV P147L;S149A 139;149 144;154 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. The P147L and S149A assembly properties and core architecture are also of great interest. 2011 Virology Discussion HIV P147L;S149A 4;14 9;19 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. The S146A mutation may not impact infectivity because this residue is exposed on the surface of the protein (A.M. 2011 Virology Discussion HIV S146A 4 9 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Thus, despite the instability of P147L and S149A cores. 2011 Virology Discussion HIV P147L;S149A 33;43 38;48 22036671 The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. Thus, the lack of infectivity of L151A is consistent with the structural data (Table 1). 2011 Virology Discussion HIV L151A 33 38 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. According to the genotypic resistance interpretation, the TDR mutations found in 71 patients mainly affect the NNRTI-based therapy, the first choice in Spain for naive patients, due to the presence of K103N, the most frequent mutation in the study especially among SSA. 2011 PloS one Discussion HIV K103N 201 206 NNRTI 111 116 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. Despite its transmission as a singleton mutation, K103N seriously compromises the use of efavirenz or nevirapine. 2011 PloS one Discussion HIV K103N 50 55 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. Finally, the surprisingly high rate in native Spanish of RT-M184I/V (4.4%), a mutation rapidly cleared due to its cost in terms of viral fitness, might reflect an unrecorded previous treatment exposure in some patients. 2011 PloS one Discussion HIV M184I;M184V 60;60 67;67 RT 57 59 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. On the other hand, the correlation between HIV subtype and birth place of the patients could also have confused the different mutational pattern described: the preferential presence of NRTI-resistance mutation M184I/V in SSA compared to T215revertants in Spanish and CSA could appear to be associated to the infection by non-B variants and subtype B, respectively, as reported in other countries. 2011 PloS one Discussion HIV M184I;M184V 210;210 217;217 NRTI 185 189 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. Our observation of a lower viral load among patients infected with variants carrying M184I/V has previously been described due to the fitness reduction related to its acquisition. 2011 PloS one Discussion HIV M184I;M184V 85;85 92;92 22046345 Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. Since TDR is expected to increase in developing regions as treatment is implemented, the presented results highlight the importance of a specific TDR surveillance among immigrants living in high-income countries to prevent future therapeutic failures, especially when administering NNRTI due to the high K103N prevalence. 2011 PloS one Discussion HIV K103N 304 309 NNRTI 282 287 22078557 Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Additionally, our results support the conclusion that the capsid E45A mutation confers increased core stability, as these particles undergo delayed capsid disassembly in target cells compared with wild-type HIV-1 under the same conditions. 2011 Structure (London, England Discussion HIV E45A 65 69 Capsid;Capsid 58;148 64;154 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Finally I62V seemed to have a marginal negative impact on viral response, especially when detected in the absence of V82A. 2011 PloS one Discussion HIV I62V;V82A 8;117 12;121 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. In addition, we identified previously unrecognized mutations I62V ad K20I, which appear to have a modest impact in reducing viral response, and mutations I15V and V91S which, in contrast, seem to determine LPV/r hypersensitivity, all of which need further investigation. 2011 PloS one Discussion HIV I15V;I62V;K20I;V91S 154;61;69;163 158;65;73;167 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. In the Stanford IS this mutation is currently given a weight of +25 which is the 2nd highest weight, after that given to I47A (weight = +50) while the Rega IS assign a weight of 0.6, remarkably similar to ours but about half the weight given to I54V (Table S1). 2011 PloS one Discussion HIV I47A;I54V 121;245 125;249 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Indeed, in our analysis whilst we found evidence that the weight for mutation I62V should be different according to whether A82V was also detected, the incorporation of this information did not lead to an improvement in predictions. 2011 PloS one Discussion HIV A82V;I62V 124;78 128;82 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Interestingly, mutation V82A was the first to be entered in our model leading to the largest decrease in ASE besides pre-TCE viral load while V82F which was more prevalent than V82A was not selected at all. 2011 PloS one Discussion HIV V82A;V82A;V82F 24;177;142 28;181;146 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Mutations K20I and I54V were given smaller weights in our score which is consistent with the fact that are not major IAS-USA mutations but are listed in most available IS (I54V is not included in ANRS). 2011 PloS one Discussion HIV I54V;I54V;K20I 19;172;10 23;177;14 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Of note, the weight of I62V was shrunk to zero by the LASSO procedure suggesting that this was a spurious association due to chance alone. 2011 PloS one Discussion HIV I62V 23 27 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Regarding the mutations included in our LPV/r score, besides mutations I15V and V91S which seemed to be not currently recognized polymorphisms associated with a better response to LPV/r, V82A is listed by IAS-USA December 2010 as a major LPV/r mutation and used in the rules of all previously developed scores (Abbott 2007 score ANRS and Rega IS and Food and Drug Association (FDA) LPV/r mutations list). 2011 PloS one Discussion HIV I15V;V82A;V91S 71;187;80 75;191;84 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. Two of the identified mutations (V82A ad I54V) in our score are recognized LPV/r mutations listed by widely used expert-based IS. 2011 PloS one Discussion HIV I54V;V82A 41;33 45;38 22110581 Can linear regression modeling help clinicians in the interpretation of genotypic resistance data? An application to derive a lopinavir-score. V32I, I47V, L76V) was relatively low and this could have influenced the covariate selection for our score. 2011 PloS one Discussion HIV I47V;L76V;V32I 6;12;0 10;16;4 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. also found that K103N, V106M and P225H were among the 16 NNRTI mutations preferentially selected by EFV and K101E, Y181C and G190A among the 12 mutations preferentially selected by NVP. 2011 PloS one Discussion HIV G190A;K101E;K103N;P225H;V106M;Y181C 125;108;16;33;23;115 130;113;21;38;28;120 NNRTI 57 62 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Also we found that tenofovir use was associated with a significantly lower rate of M184V mutation than d4T, illustrated in Figure 2B, while this was not observed in the 903 study which evaluated the efficacy and safety of tenofovir vs stavudine when combined with 3TC and Efavirenz in antiretroviral-naive patients. 2011 PloS one Discussion HIV M184V 83 88 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Conversely, the clear negative association of viral load at genotyping and occurrence of mutations M184V and V108I can be interpreted as an effect of these mutations on viral fitness. 2011 PloS one Discussion HIV M184V;V108I 99;109 104;114 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. EFV sensitivity is likely due to the Y181C mutation, as reported by other groups. 2011 PloS one Discussion HIV Y181C 37 42 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. However, in their analysis of covariation of NNRTI resistance mutations, the K103N-P225H pair as well the Y181C-G190A and K101E-Y181C pairs significantly covaried in sequences from individuals experiencing EFV while the pair V108I-Y181C covaried in NVP group and the pair K101E-G190E covaried in both groups. 2011 PloS one Discussion HIV G190A;G190E;K101E;K101E;K103N;P225H;V108I;Y181C;Y181C;Y181C 112;278;122;272;77;83;225;106;128;231 117;283;127;277;82;88;230;111;133;236 NNRTI 45 50 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. In contrast, we confirmed the observation that K65R has an antagonistic effect with TAMs, since only 1 of 9 patients in our study had both 65R and one TAM. 2011 PloS one Discussion HIV K65R 47 51 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Less expected was our finding that the major NRTI mutations M184V and K65R were preferentially selected in the presence of nevirapine (Figures 1B and 2A), while TAM-1 mutations were almost never selected (only in 2% of patients treated by nevirapine). 2011 PloS one Discussion HIV K65R;M184V 70;60 74;65 NRTI 45 49 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Our analysis offers strong evidence that, in contrast to the mutation patterns published for other subtypes, individuals infected with CRF01_AE and experiencing virologic failure while receiving NVP-based HAART favor TAM-2 resistance pathways (K70R, D67N, T215F, K219Q/E) rather than TAM-1 (M41L, L210W, T215Y), whereas those receiving regimens containing EFV appear to select both TAM-2 and TAM-1 pathways (Figures 1B, 2A and 3B). 2011 PloS one Discussion HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 250;263;263;244;297;291;256;304 254;270;270;248;302;295;261;309 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Our analysis, shown in Figure 2D, confirmed that the M184I mutation occurs before M184V, suggested that K103N is an early mutation, and showed clearly that all the TAM-2 pathway mutations, as well as 215Y, occur as time spent on virologic failure increases. 2011 PloS one Discussion HIV K103N;M184I;M184V 104;53;82 109;58;87 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. Our model-based analysis suggested that tenofovir, in addition to selecting K65R, also strongly selected Y115F (Figure 2B), a mutation rarely observed in other subtypes, and then only with the use of a triple-NRTI regimen. 2011 PloS one Discussion HIV K65R;Y115F 76;105 80;110 NRTI 209 213 22132100 Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. The synergistic association of tenofovir and efavirenz is also supported by the fact that efavirenz was shown to protect from K65R and Y115F. 2011 PloS one Discussion HIV K65R;Y115F 126;135 130;140 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Although our goal was to design an antigen that prevents binding of all poorly neutralizing CD4bs mAbs, the ability of mAbs b6 and b13, both of which neutralize poorly, to recognize mutant Q105N suggests that future studies may need to explore strategies such as heterologous prime-boosting to selectively promote antibody responses to the b12 site. 2012 Vaccine Discussion HIV Q105N 189 194 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Despite the suboptimal antigenic profile of mutant Q105N, Q105N_QuilA sera did bind strongest overall to RSC3, providing support for the use of Q105N to preferentially stimulate CD4bs responses. 2012 Vaccine Discussion HIV Q105N;Q105N;Q105N 51;144;58 56;149;63 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Disappointingly, we observed no significant neutralizing activity with the Q105N_QuilA sera or any of the other 3 sera against the tier 1 and 2 subtype B and C pseudoviruses tested. 2012 Vaccine Discussion HIV Q105N 75 80 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. In summary, we have shown that hyperglycosylated gp120 mutant Q105N can be used to induce relatively greater responses to the CD4bs, particularly when formulated with adjuvant Quil A. 2012 Vaccine Discussion HIV Q105N 62 67 gp120 49 54 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Our results show that the hyperglycosylated gp120 mutant Q105N selectively limits exposure of the CD4bs without loss of immunogenicity. 2012 Vaccine Discussion HIV Q105N 57 62 gp120 44 49 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. The observation that antibodies elicited with Q105N_QuilA bound the RSC3Delta371I mutant to similar levels as the parent molecule RSC3 was unexpected given that this residue is normally a critical binding residue for CD4bs antibodies. 2012 Vaccine Discussion HIV Q105N 46 51 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Unfortunately, due to serum volume limitations we were not able to assess whether HJ16 binding was also blocked by the Q105N_QuilA serum antibodies. 2012 Vaccine Discussion HIV Q105N 119 124 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. We did not observe any difference in the overall level of antibody titres between gp120wt and Q105N. 2012 Vaccine Discussion HIV Q105N 94 99 22142583 An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Whether the glycosylation pattern of Q105N played a pivotal role in the quality of the antibody responses elicited here remains to be determined. 2012 Vaccine Discussion HIV Q105N 37 42 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. However, while the Q151N HIV-1 RT mutation reduces the dNTP binding affinity through a lost interaction with the sugar moiety of a dNTP substrate, the bulky mutations at 114 appears to reduce the dNTP binding affinity by occupying the space in the pocket where the sugar moiety of dNTP normally binds RT. 2012 Virology Discussion HIV Q151N 19 24 RT;RT 31;301 33;303 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. In addition the mutations that were generated in this study had minimal impact on the processivity of RT with the exception of A114V (Figure 1S). 2012 Virology Discussion HIV A114V 127 132 RT 102 104 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Interestingly, as shown in Table 2, the A114C mutation prompted a larger increase in the Kd values of purine nucleotide substrates when compared to pyrimidine nucleotides. 2012 Virology Discussion HIV A114C 40 45 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Our biochemical and virological results support that like the Q151N HIV-1 RT mutant, the A114 RT mutants enzymatically mimic oncoretroviral RTs such as MuLV RT and Avian Sarcoma Virus (ASV) RT which both efficiently synthesize DNA only at the high dNTP concentrations found in dividing cells. 2012 Virology Discussion HIV Q151N 62 67 RT;RT;RT;RT;RT 74;94;140;157;190 76;96;143;159;192 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The mutation A114C might reduces this space, causing a decrease in the binding of purine substrates to RT and an increase in their Kd. 2012 Virology Discussion HIV A114C 13 18 RT 103 105 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. The Q151N mutation was found to significantly reduced not only the dNTP binding affinity of RT but also the transduction of HIV-1 vectors bearing the Q151N mutation in cells containing low dNTP concentrations. 2012 Virology Discussion HIV Q151N;Q151N 4;150 9;155 RT 92 94 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. Therefore, it is possible that the A114C mutation structurally influences the steric gate residue of HIV-1 RT, Tyr115. 2012 Virology Discussion HIV A114C 35 40 RT 107 109 22153297 The impact of molecular manipulation in residue 114 of human immunodeficiency virus type-1 reverse transcriptase on dNTP substrate binding and viral replication. This suggests that the A114V mutations may result in larger structural changes that affect RTs interaction with the template primers as well as dNTPs. 2012 Virology Discussion HIV A114V 23 28 RT 91 94 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. Furthermore, mutations that render HIV-1 less sensitive to both Nup358 and TRN-SR2 depletion (CA N57A and N74D) both shift integration preferences to regions with lower densities of transcription units (Figure 4). 2011 PLoS pathogens Discussion HIV N57A;N74D 97;106 101;110 Capsid 94 96 22174692 HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. G89V), and inhibiting CypA binding with Cs, both lead to increased frequency of integration in regions with higher densities of transcription units (Figure 4 and 5), supporting the consistency of our observations. 2011 PLoS pathogens Discussion HIV G89V 0 4 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. An intriguing question remains regarding the pleiotropic effects of the mutation W131A on HIV-1 replication. 2011 Retrovirology Discussion HIV W131A 81 86 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Consistent with previous results, we found that IN K188Q mutant was predominantly monomeric (Figure 2) and showed almost 3-fold decrease for LEDGF/p75 interaction (Figure 4A). 2011 Retrovirology Discussion HIV K188Q 51 56 IN 48 50 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Consistent with this observation, IN W131A reached near WT concerted integration activity at its highest concentration (Figure 3B). 2011 Retrovirology Discussion HIV W131A 37 42 IN 34 36 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Despite its SEC monomeric profile, the Q168L mutant retains some catalytic activity in vitro. 2011 Retrovirology Discussion HIV Q168L 39 44 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Furthermore, the ability of monomeric IN to interact with TNPO3 was further confirmed with the mutant K188Q. 2011 Retrovirology Discussion HIV K188Q 102 107 IN 38 40 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. In addition, HIV-1 viruses carrying IN deletion or the C130S substitution were recently described to decrease CypA-CA interaction leading to the destabilization of the viral core. 2011 Retrovirology Discussion HIV C130S 55 60 IN;Capsid 36;115 38;117 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. In sharp contrast, Y194F displayed WT SEC profile and retained high affinity for LEDGF/p75. 2011 Retrovirology Discussion HIV Y194F 19 24 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Indeed, W131A and Q168L displayed the strongest decreases in TNPO3 binding while showing opposite oligomerization profiles. 2011 Retrovirology Discussion HIV Q168L;W131A 18;8 23;13 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Mutation Y194E was also compromised for tetramer formation, although to a lesser extent, as tetramers forms were still present. 2011 Retrovirology Discussion HIV Y194E 9 14 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Mutations Q168L, K188Q and Y194E that destabilized IN multimers also affected LEDGF/p75 binding in our HTRF assay. 2011 Retrovirology Discussion HIV K188Q;Q168L;Y194E 17;10;27 22;15;32 IN 51 53 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. On the contrary, the W131A mutant displayed in vitro catalytic activities as well as multimerization profile similar to the wild type IN, indicating that this mutation has limited impact on the conformation of the protein. 2011 Retrovirology Discussion HIV W131A 21 26 IN 134 136 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Our interaction assays indicate that IN mutants W131A and Q168L are the most deficient for TNPO3 interaction. 2011 Retrovirology Discussion HIV Q168L;W131A 58;48 63;53 IN 37 39 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Recently, HIV-1 CA mutant N74D was shown to escape replication restriction observed upon TNPO3 depletion. 2011 Retrovirology Discussion HIV N74D 26 30 Capsid 16 18 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Results from our HTRF assay confirmed previous studies showing that both IN W131A and IN W131D were defective for LEDGF/p75 binding in His-IN pull down assays. 2011 Retrovirology Discussion HIV W131A;W131D 76;89 81;94 IN;IN;IN 73;86;139 75;88;141 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. The elution profile of W131A resembled the one of IN WT consisting of a mixture of mono-, di- and tetramers with a predominance of dimeric forms (Figure 2). 2011 Retrovirology Discussion HIV W131A 23 28 IN 50 52 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. The Q168L mutant behaved solely as a monomer, confirming that alteration of the conformation of the CCD alpha4/alpha5 connector reduces IN affinity for LEDGF/p75 (Figure 4A). 2011 Retrovirology Discussion HIV Q168L 4 9 IN 136 138 22176773 Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. This is exemplified by the ability of the mutant Q168L to retain partial concerted integration activity (Figure 3B), suggesting that the monomeric IN Q168L could oligomerize in presence of DNA. 2011 Retrovirology Discussion HIV Q168L;Q168L 49;150 54;155 IN 147 149 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. A similar pattern was displayed by isolates from our study, 50% of these harbouring the L89M polymorphism, while only 5.3% the L90M mutation. 2011 Romanian biotechnological letters Discussion HIV L89M;L90M 88;127 92;131 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. Group O viruses are resistant to this class of antiretroviral drugs, resistance develops faster in subtype C, due to selection of V106M and resistance to nevirapine after its administration for prevention of mother-to-child transmission in Uganda was more frequently encountered in subtype D than in subtype A. 2011 Romanian biotechnological letters Discussion HIV V106M 130 135 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. I93L, found in two F1 patients from this study, one susceptible to all PIs and another one with low degree resistance to some of the class compounds is a secondary resistance mutation in subtype B that causes hyper susceptibility to PIs in subtype C isolates. 2011 Romanian biotechnological letters Discussion HIV I93L 0 4 PI;PI 71;233 74;236 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. Regarding protease inhibitors susceptibility, in Brazilian subtype F1 isolates, presence of the L89M polymorphism in the protease gene was related to the maintenance of viral fitness, conferring a higher genetic barrier to the accumulation of the L90M resistance mutation, the latter being considered a predictor of failure to Kaletra-based regimens. 2011 Romanian biotechnological letters Discussion HIV L89M;L90M 96;247 100;251 PR;PR 10;121 18;129 22180722 Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients. The M89I mutation, found to emerge in F, G, and C subtypes after nelfinavir failure, and also associated with increased susceptibility to other PIs, except for lopinavir, was not found in our group. 2011 Romanian biotechnological letters Discussion HIV M89I 4 8 PI 144 147 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Indeed, our NMR data of wt Vpr75-90 and Vpr75-90 R80A confirmed this interpretation and revealed that the propensity for weak helical structure of the C-terminal binding region is essentially unaffected by the mutation of Arg-80 to Ala (Figure 3). 2011 BMC structural biology Discussion HIV R80A 222 235 Vpr;Vpr 27;40 30;43 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Mutation of the central Pro residue (P35A) causes a loss of binding through disruption of the Pro-dependent N-terminal heptapeptide binding region. 2011 BMC structural biology Discussion HIV P35A 37 41 22185200 The host-pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains. Previous studies have shown that the mutants Vpr P35A and Vpr R80A were key residues for coimmunoprecipitation of Vpr and CypA, and when replaced abrogated the coimmunoprecipitation to CypA. 2011 BMC structural biology Discussion HIV P35A;R80A 49;62 53;66 Vpr;Vpr;Vpr 45;58;114 48;61;117 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. Among the RT sequences, 2 of the 44 viruses (4.5%) harbored the K103N substitution, which confers resistance to nevirapine, and it also occurred in combination with V90I in one virus. 2012 Archives of virology Discussion HIV K103N;V90I 64;165 69;169 RT 10 12 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. However, that study reported 46% prevalence for K20R and 8% for V82I, which are higher than the findings in the current study. 2012 Archives of virology Discussion HIV K20R;V82I 48;64 52;68 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. M36I occurred in 28 viruses (98%), T74S occurred in two viruses (7%), I93L occurred in 27 isolates with a prevalence of 93%, and V82I occurred in one virus (3.4%). 2012 Archives of virology Discussion HIV I93L;T74S;V82I;M36I 70;35;129;0 74;39;133;4 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. One of the viruses harbored the combination V118I/E138A/V179D, while another had V118I/E138A. 2012 Archives of virology Discussion HIV E138A;V118I;V179D;E138A;V118I 50;44;56;87;81 55;49;61;92;86 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. Other substitutions that were found include V90I, E138A, and V179D, which are weakly associated with decreased NNRTI susceptibility, and V118I, which occurs in ~2% of untreated individuals and with increased frequency in those receiving multiple NRTIs. 2012 Archives of virology Discussion HIV E138A;V118I;V179D;V90I 50;137;61;44 55;142;66;48 NNRTI;NRTI 111;246 116;251 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. Our earlier study did not find K103N among the study participants. 2012 Archives of virology Discussion HIV K103N 31 36 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. The finding of K103N, which results in nevirapine resistance, in 4.5% of the study population is of importance, as nevirapine is used in the prevention of mother-to-child transmission of HIV. 2012 Archives of virology Discussion HIV K103N 15 20 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. The secondary substitution was L10V in two viruses (7%), whereas K20R occurred in four (14%) of the 29 isolates. 2012 Archives of virology Discussion HIV K20R;L10V 65;31 69;35 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. These mutations have been reported to cause low-level resistance when they occur alone and increased resistance when they occur in combination with other mutations like E44A/D (http://hivdb.stanford.edu/). 2012 Archives of virology Discussion HIV E44A;E44D 169;169 175;175 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. These observations are similar to those of a previous report, with 93% prevalence for both M36I and I93L. 2012 Archives of virology Discussion HIV I93L;M36I 100;91 104;95 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. This latter substitution is known to cause low-level resistance to lamivudine and possibly to other NRTIs when present with E44A/D and/or one or more TAMs. 2012 Archives of virology Discussion HIV E44A;E44D 124;124 130;130 NRTI 100 105 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. V118I is a polymorphism in non-B RT that is associated with subtype B NRTI resistance. 2012 Archives of virology Discussion HIV V118I 0 5 NRTI;RT 70;33 74;35 22189822 Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. We also found six viruses (13.9%) that harbored A98S and four (9.3%) with V179I, which is lower than the 15% and 23%, respectively, that were previously reported in the province. 2012 Archives of virology Discussion HIV A98S;V179I 48;74 52;79 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. For example, the use of NVP can lead to emergence of Y181C which results in a significant reduction in the susceptibility to ETR, whereas the emergence of K103N from the use of EFV does not affect drug susceptibility to second generation ETR. 2012 Antiviral therapy Discussion HIV K103N;Y181C 155;53 160;58 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Furthermore, only one participant in this study harbored TAMs, in complete contrast to all other published studies from the region which report levels of 23% to 56% and the Q151M mutation was not observed. 2012 Antiviral therapy Discussion HIV Q151M 173 178 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Furthermore, the presence of K65R may have implications for TDF usage in pre-exposure prophylaxis (PREP) and further investigation is required into transmission and fitness of viruses with K65R. 2012 Antiviral therapy Discussion HIV K65R;K65R 29;189 33;193 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. NVP uniquely selected for Y181C (41%) and the V106A (9%) and both the K103N and V106M mutations were more frequent in participants accessing EFV. 2012 Antiviral therapy Discussion HIV K103N;V106A;V106M;Y181C 70;46;80;26 75;51;85;31 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The increased frequency of K65R has been linked to nucleotide changes in the sequence prior to codon 65 in HIV subtype C. 2012 Antiviral therapy Discussion HIV K65R 27 31 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The K103N (41%) mutation was the most frequent NNRTI mutation observed. 2012 Antiviral therapy Discussion HIV K103N 4 9 NNRTI 47 52 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The K65R mutation results in broad cross-resistance to NRTIs and has consequences for the subsequent use of most NRTIs, especially tenofovir (TDF) in second-line regimens possibly making it better suited in first-line regimens. 2012 Antiviral therapy Discussion HIV K65R 4 8 NRTI;NRTI 55;113 60;118 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The most frequently observed mutations were M184V (57%), K103N (46%) and Y181C (21%). 2012 Antiviral therapy Discussion HIV K103N;M184V;Y181C 57;44;73 62;49;78 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The mutation patterns were less complex than those reported in published data from the region, K65R (3%) was considerably lower than that observed in first-line failures in previously published data from Malawi and South Africa, which showed M184V present in up to 81% and K65R present in up to 19%. 2012 Antiviral therapy Discussion HIV K65R;K65R;M184V 95;273;242 99;277;247 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The mutations K65R and TAMs were observed infrequently, and the Q151M was not present at all, thereby preserving the use of AZT, ddI or TNF used in second-line regimens. 2012 Antiviral therapy Discussion HIV K65R;Q151M 14;64 18;69 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. The second most frequent NRTI mutation observed was K65R (3%), which is uncommon in HIV-1 subtype B infected patients receiving d4T. 2012 Antiviral therapy Discussion HIV K65R 52 56 NRTI 25 29 22293461 Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. These NNRTI mutation patterns are the same as those observed in the South African public sector programme with K103N being the most prevalent. 2012 Antiviral therapy Discussion HIV K103N 111 116 NNRTI 6 11 22331986 HIV Drug Resistance-Associated Mutations in Antiretroviral Naive HIV-1-Infected Latin American Children. In comparison to other studies, this rate of primary drug resistance is lower than that reported in children in Northeast Brazil and higher than the 0% rate reported in 24 children in Sao Paulo, Brazil (although reverse transcriptase mutation K219N was seen in one subject in the latter study, which, by our definition, yields a rate of 4.2%). 2010 Advances in virology Discussion HIV K219N 243 248 RT 212 233 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Eleven of 24 patients had low or high level M184V/I variants; 7 had M184V/I at >=1% of the viral population, however only 4 of the 7 developed phenotypic resistance to FTC/3TC (all had M184V variant levels >95%). 2012 PloS one Discussion HIV M184I;M184I;M184V;M184V;M184V 44;68;44;68;185 51;75;51;75;190 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. Interestingly, not all patients with M184V/I developed phenotypic resistance to FTC/3TC. 2012 PloS one Discussion HIV M184I;M184V 37;37 44;44 22355307 Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing. None of the patients with K65R (all at <2%) developed phenotypic resistance to TDF (See Table S1). 2012 PloS one Discussion HIV K65R 26 30 22359615 HIV-1 subtype D infections among Caucasians from Northwestern Poland--phylogenetic and clinical analysis. Additionally, the high frequency of primary drug resistance mutations (DRMs) observed in this study was associated to the observed clustering within the network of transmission and presence of M41L and T215 revertant mutations. 2012 PloS one Discussion HIV M41L 193 197 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Although our sample size is small (N = 23), this is surprising given that N348I and A360V mutations decrease AZT susceptibility to the same extent (this study,). 2012 PloS one Discussion HIV A360V;N348I 84;74 89;79 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. As a result, both the selection of A360V during AZT monotherapy and resistance to AZT from A360V are unequivocally shown. 2012 PloS one Discussion HIV A360V;A360V 35;91 40;96 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. By contrast, the Q509L mutation was not present in any of the sequences. 2012 PloS one Discussion HIV Q509L 17 22 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. By contrast, von Wyl et al reported that N348I predominantly emerged in participants receiving lamivudine and AZT, whereas Hachiya et al reported that N348I emerged on AZT- and/or ddI-containing therapies. 2012 PloS one Discussion HIV N348I;N348I 41;151 46;156 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. For example, Yap et al reported that failure of AZT and nevirapine therapy was associated with the emergence of N348I, TAMs, and the non-nucleoside RT inhibitor resistance mutations K103N, V108I, Y181C/I and G190A/S. 2012 PloS one Discussion HIV G190A;G190S;K103N;N348I;V108I;Y181C;Y181I 208;208;182;112;189;196;196 215;215;187;117;194;203;203 RT 148 150 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Importantly, we also show that the A360V mutation confers ~2.0-fold AZT resistance both in the full-length RT sequence context it was selected in vivo and in the xxLAI molecular clone. 2012 PloS one Discussion HIV A360V 35 40 RT 107 109 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. In summary, this study of full-length RT sequences from paired pre- and post-therapy samples shows that the A360V mutation in the connection domain of RT emerges on AZT monotherapy with similar frequency as TAMs in the polymerase domain and confers ~2-fold resistance to AZT through an excision-promoting molecular mechanism. 2012 PloS one Discussion HIV A360V 108 113 Pol;RT;RT 219;38;151 229;40;153 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. In the 23 on-treatment samples sequenced in the current study, we noted a strong trend (p = 0.06) toward selection of A371V with AZT monotherapy. 2012 PloS one Discussion HIV A371V 118 123 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Longitudinal analyses also showed that A360V was detected at the same time or after the appearance of TAMs but not before. 2012 PloS one Discussion HIV A360V 39 44 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Of note, the A360V mutation has not been associated with failure of any specific drug combinations. 2012 PloS one Discussion HIV A360V 13 18 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Of note, the N348I mutation was not identified in any of the sequences in this study. 2012 PloS one Discussion HIV N348I 13 18 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Our analyses reveal that the A360V mutation in the connection domain emerged with similar or higher frequency as TAMs M41L, D67N, L210W and K219E/Q. 2012 PloS one Discussion HIV A360V;D67N;K219E;K219Q;L210W;M41L 29;124;140;140;130;118 34;128;147;147;135;122 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. Recent studies show that RT inhibitors select for drug resistance mutations in the connection domain of RT including N348I and the A360V mutation reported here. 2012 PloS one Discussion HIV A360V;N348I 131;117 136;122 RT;RT 25;104 27;106 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. The A360V mutation was not selected. 2012 PloS one Discussion HIV A360V 4 9 22363673 Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase. We previously reported that in in vitro selection experiments HIV-1 selected for two novel mutations - A371V in the connection domain and Q509L in the RNase H domain - in combination with D67N, K70R and T215F that together conferred greater than 100-fold AZT resistance. 2012 PloS one Discussion HIV A371V;D67N;K70R;Q509L;T215F 103;188;194;138;203 108;192;198;143;208 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. 7/11 women with HIV-1 carrying AZT-selected mutants displayed the K70R mutation in proportions of 3%-28%, whereas T215Y/F-carrying virus was harbored in lower proportions of 0.5%-3.9% by four women. 2012 PloS one Discussion HIV K70R;T215F;T215Y 66;114;114 70;121;121 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. However, population-based sequencing, detecting minor variants in proportions only above 20%, revealed AZT-resistance mutations (K70R) in HIV-1 of only 4 women (8%). 2012 PloS one Discussion HIV K70R 129 133 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. In fact, the K70R mutation is considered to be an early AZT mutation and indicates the emergence of AZT-resistance followed by M41L, T215Y/F and L210W. 2012 PloS one Discussion HIV K70R;L210W;M41L;T215F;T215Y 13;145;127;133;133 17;150;131;140;140 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. It is important to note that the K70R mutation affecting HIV-1 of 7/50 (14%) women confers low level resistance towards AZT, whereas T215Y and T215F mutations affecting virus of 4/50 (8%) women result in high-level resistance. 2012 PloS one Discussion HIV K70R;T215F;T215Y 33;143;133 37;148;138 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. K70R was the most frequently observed AZT mutation in samples taken at delivery (n = 5), while T215Y and T215F mutations mostly emerged later during the observation period. 2012 PloS one Discussion HIV T215F;T215Y;K70R 105;95;0 110;100;4 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Moreover, M184V is known to be rapidly lost upon withdrawal of 3TC. 2012 PloS one Discussion HIV M184V 10 15 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. reported of successful treatment despite pre-existing minor K65R, K103N and M184V-variants in German Truvada cohort, several other studies have shown that the presence of drug-resistant minor variants increased the risk for subsequent treatment failure for NNRTI-, protease inhibitor- and AZT-containing treatment. 2012 PloS one Discussion HIV K103N;K65R;M184V 66;60;76 71;64;81 PR;NNRTI 265;257 273;262 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. Since the AZT resistance mutation T215Y was shown to persist for several month, resistant variants could be re-selected if exposed to prophylactic AZT in future pregnancies or during subsequent AZT-containing HAART if initiated within this period after AZT exposure. 2012 PloS one Discussion HIV T215Y 34 39 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. The M184V mutation results in complete resistance to 3TC and the presence of postpartum M184V in proportions >20% has been correlated to subsequent treatment failure using 3TC-containing HAART. 2012 PloS one Discussion HIV M184V;M184V 4;88 9;93 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. The shortest interval between start of AZT exposure and the emergence of AZT-selected mutation K70R was 28 days only. 2012 PloS one Discussion HIV K70R 95 99 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. This might be due to the fact that for K70R one base substitution is sufficient (AAA/AAG to AGA/AGG) while for T215Y and F two base mutations are required (ACC to TAC = >T215Y or TTC = >T215F). 2012 PloS one Discussion HIV K70R;T215F;T215Y;T215Y 39;186;111;170 43;191;116;175 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. While a single NNRTI-resistance mutation confers high-level resistance to some NNRTIs (an association with virologic failure in efavirenz-containing regimen was found for K103N variants at frequencies of > = 0.5% by Halvas et al.), resistance to PI and AZT requires an accumulation of several mutations. 2012 PloS one Discussion HIV K103N 171 176 NNRTI;NNRTI;PI 15;79;246 20;85;248 22384138 Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission. While emergence of K70R is transient, AZT-resistant mutation T215Y is reported to persist for several months up to more than one year even after AZT discontinuation. 2012 PloS one Discussion HIV K70R;T215Y 19;61 23;66 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. A comparable pattern appeared with Vpx K68A and K77A, while Vpx K84A and TA had no evidence of modification by either endogenous or exogenous ubiquitin. 2012 Virology Discussion HIV K68A;K77A;K84A 39;48;64 43;52;68 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Also, our results demonstrate that Vpx K68A mutant has severely decreased binding with DCAF1, whereas, the Vpx K84A mutant interacts with DCAF1. 2012 Virology Discussion HIV K68A;K84A 39;111 43;115 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. However, virions with Vpx TA, K68A, and K77A mutants had severely impaired early and late reverse transcription products compared to the products obtained with ES or with Vpx Wt virions, indicating that mutations at positions K68 and K77 are detrimental to reverse transcription. 2012 Virology Discussion HIV K68A;K77A 30;40 34;44 RT;RT 90;257 111;278 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. Interestingly, Vpx mutation K84A had no effect on early or late reverse transcription product levels and the levels were similar to those observed with Vpx Wt and ES, indicating that Vpx ubiquitination is dispensable for replication in MDMs. 2012 Virology Discussion HIV K84A 28 32 RT 64 85 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. These results are consistent with the results reported by Sharova and colleagues, in which SIV Vpx K84R mutant had the greatest defect in ubiquitination. 2012 Virology Discussion HIV K84R 99 103 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. We observed that our HIV-2 Vpx K84A mutant lacked ubiquitination even though other lysine residues were present in Vpx, at positions 68 and 77. 2012 Virology Discussion HIV K84A 31 35 22386056 HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection. With our Vpx lysine mutants, we found that while Vpx Wt was ubiquitinated, marked by the presence of ubiquitin bands detected with Flag mAb, Vpx TA mutant lost all ubiquitination, as did the Vpx K84A mutant. 2012 Virology Discussion HIV K84A 195 199 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. A comparison of various inhibitor bound V82A mutant structures shows increased variability of the conformation of 80s loop, which suggested the Val82 side chain plays a role in stabilizing the loop. 2012 Journal of medicinal chemistry Discussion HIV V82A 40 44 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Furthermore, kinetic studies showed the mutation of A28S significantly reduces the catalytic activity of the enzyme and viral infectivity, consistent with the absence of this mutation in clinical isolates. 2012 Journal of medicinal chemistry Discussion HIV A28S 52 56 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. In the mutant structure, I47V loses contacts with neighboring residues, which would potentially decrease the stability of the flaps as suggested by molecular dynamics simulations. 2012 Journal of medicinal chemistry Discussion HIV I47V 25 29 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Moreover, D30N is one of the major mutations associated with NFV resistance. 2012 Journal of medicinal chemistry Discussion HIV D30N 10 14 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. Superposition of PRWT/1 and PRA28S/U-89360E (PDB ID 3H5B and 1AXA) suggests the A28S side chain may form multiple interactions with p-methoxysulfonamide and Cp-THF of inhibitor 1. 2012 Journal of medicinal chemistry Discussion HIV A28S 80 84 PR 28 30 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. The A28S mutation was identified in the UIC-94003 (also referred to as TMC-126) or GRL-1398 treated laboratory HIV-1 variants, suggesting an association between the presence of p-methoxysulfonamide in both compounds and the development of A28S resistance mutation. 2012 Journal of medicinal chemistry Discussion HIV A28S;A28S 4;239 8;243 22401672 Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of drug resistant mutants with its P1'-pyrrolidinone ring. The dynamic side chain position of Asp30 has been observed in various D30N single mutants and double mutants such as D30N/N88D and D30N/N88S. 2012 Journal of medicinal chemistry Discussion HIV D30N;D30N;D30N;N88D;N88S 70;117;131;122;136 74;121;135;126;140 Asp 35 38 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. It is difficult to estimate how often onward transmission occurred in our study, but it is likely that some of the 18 patients in the M41L cluster represent onward transmission because it is improbable that one patient transmitted to all others. 2012 PloS one Discussion HIV M41L 134 138 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. One cluster was large and contained 18 viruses with the M41L resistance mutation. 2012 PloS one Discussion HIV M41L 56 60 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. The first patient in this transmission cluster was infected in 1994 (or earlier) and the last two in 2010, which shows that this virus variant has been transmitted in Stockholm over a period of at least 16 years and that the M41L mutation is very stable. 2012 PloS one Discussion HIV M41L 225 229 22448246 Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV-1 infection in Sweden 2003-2010. This M41L cluster represents continued spread of a virus variant that has already has been reported in seven MSM in Stockholm. 2012 PloS one Discussion HIV M41L 5 9 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. An assessment of the sensitivities of these two backbones to measuring resistance in the presence of the M184V, K103N, or V106M mutation was performed. 2012 PloS one Discussion HIV K103N;M184V;V106M 112;105;122 117;110;127 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. Another minor restriction of this analysis is that the majority of recombinant viruses carried the M184V, the K103N and the V106M mutations, which provide high-level resistance to 3TC and FTC with M184V or EFV and NVP with K103N and V106M. 2012 PloS one Discussion HIV K103N;K103N;M184V;M184V;V106M;V106M 110;223;99;197;124;233 115;228;104;202;129;238 22496845 HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone. It would have been of interest to look at the K65R and thymidine analogue mutations (TAMs), but there were insufficient data points available for appropriate ROC analysis to be performed. 2012 PloS one Discussion HIV K65R 46 50 22496972 Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India. In earlier studies from India, M184V was found in two of 128 (1.6%) cases by Deshpande et al. 2012 AIDS research and treatment Discussion HIV M184V 31 36 22496972 Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India. In our study M184V, an RT mutation, which confers resistance to lamivudine was isolated in one case. 2012 AIDS research and treatment Discussion HIV M184V 13 18 RT 23 25 22496972 Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naive Population from Northern India. One participant (1.5%) in our study had a major PI mutation, D30N, in the protease gene. 2012 AIDS research and treatment Discussion HIV D30N 61 65 PR;PI 74;48 82;50 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. A recent cryoEM structural model of the assembled capsid may help explain how T216I, which resides in the C-terminal domain of CA, modulates the effects of the P38A substitution in the N-terminal domain. 2012 Retrovirology Discussion HIV P38A;T216I 160;78 164;83 Capsid;Capsid 50;127 56;129 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Alternatively, the E45A mutation might affect the network of water-mediated hydrogen bonds observed at the NTD-NTD interface in the X-ray crystal structure, with R132T mutation partially restoring the H-bonding network. 2012 Retrovirology Discussion HIV E45A;R132T 19;162 23;167 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Apparently, the putative uncoating defect associated with the P38A and E45A mutations can be rescued in target cells without restoring normal intrinsic capsid stability. 2012 Retrovirology Discussion HIV E45A;P38A 71;62 75;66 Capsid 152 158 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Collectively, these data strongly suggest that the E45A uncoating defect is rescued by the R132T mutation. 2012 Retrovirology Discussion HIV E45A;R132T 51;91 55;96 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. E45 is in the vicinity of this interface as well; however, the distance between these two side chains prohibits a direct interact with one another, making it unlikely that R132T directly offsets the stability defect resulting from E45A. 2012 Retrovirology Discussion HIV E45A;R132T 231;172 235;177 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Furthermore, the R132T mutation partially rescued the impaired ability of the E45A mutant to infect nondividing cells, possibly via reversal of the uncoating defect caused by the E45A mutation. 2012 Retrovirology Discussion HIV E45A;E45A;R132T 78;179;17 82;183;22 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In accordance with this hypothesis, impaired infection of nondividing cells is associated with CA mutants E45A and Q63A/Q67A, which exhibit hyperstable capsids and/or slower uncoating in target cells. 2012 Retrovirology Discussion HIV E45A;Q63A;Q67A 106;115;120 110;119;124 Capsid;Capsid 152;95 159;97 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. In the present work, we observed that the R132T and T216I mutations can partially correct the infectivity defects associated with E45A and P38A, respectively, without correcting the altered capsid stability perturbations created by the original mutations. 2012 Retrovirology Discussion HIV E45A;P38A;R132T;T216I 130;139;42;52 134;143;47;57 Capsid 190 196 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. NMR structural assessment of the effects of the mutations on the CA-NTD structure revealed no gross conformational changes in either P38A or E45A mutants, nor for the R132T mutant. 2012 Retrovirology Discussion HIV E45A;P38A;R132T 141;133;167 145;137;172 Capsid 65 67 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Our observation that R132T rescues the impaired ability of E45A mutant particles to infect arrested cells confirms that the ability of lentiviruses to infect nondividing cells is dependent on a function of the viral capsid, and suggests that this is linked to the mechanism or timing of uncoating. 2012 Retrovirology Discussion HIV E45A;R132T 59;21 63;26 Capsid 216 222 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Our results with the P38A/T216I mutant are reminiscent of another study of CA-NTD mutants in which a second-site substitution at position 208 in the CTD restored replication to mutants containing substitutions at His62 in the NTD, which were associated with structural impairments in the capsid. 2012 Retrovirology Discussion HIV P38A;T216I 21;26 25;31 Capsid;Capsid 288;75 294;77 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Similarly, the R132T suppressor restored sensitivity to PF74, a compound that inhibits HIV-1 by destabilizing the viral capsid. 2012 Retrovirology Discussion HIV R132T 15 20 Capsid 120 126 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The P38A substitution, however, resulted in more extensive changes that could be related to a general effect of the structural adjustment for the mutation. 2012 Retrovirology Discussion HIV P38A 4 8 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The R132T substitution could act by restoring the overall net charge of CA, which would be consistent with our previous findings that the stability of the HIV-1 capsid is sensitive to changes in ionic strength and pH. 2012 Retrovirology Discussion HIV R132T 4 9 Capsid;Capsid 161;72 167;74 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. The T216I mutation reversed the impaired ability of the P38A mutant to abrogate TRIMCyp- and TRIM5alpha-mediated restriction of HIV-1. 2012 Retrovirology Discussion HIV P38A;T216I 56;4 60;9 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Thus, the T216I substitution may stabilize the CTD-CTD interhexamer interface, thereby offsetting the structural effects of the P38A substitution. 2012 Retrovirology Discussion HIV P38A;T216I 128;10 132;15 22515365 Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. We previously demonstrated a correlation between efficiency of saturation of restriction and intrinsic capsid stability; therefore, the restored ability of P38A/T216I to saturate CA-specific host restriction likely results from stabilization of the viral capsid in the target cells. 2012 Retrovirology Discussion HIV P38A;T216I 156;161 160;166 Capsid;Capsid;Capsid 103;255;179 109;261;181 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. A Thr-to-Ser substitution at the same position (T244S) has been reported to be one of four changes that rescue the replication capacity of viruses resistant to virus-inhibitory peptide (VIRIP), an inhibitor corresponding to the C-proximal region of alpha1-antitrypsin. 2012 Virology Discussion HIV T244S 48 53 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Although mutation-a (G516V) confers only a very low level of VCV resistance by itself, an effect evident in PBMC but not TZM-bl cells, it is critical overall. 2012 Virology Discussion HIV G516V 21 26 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. As the genotypic and phenotypic data from the reversion culture suggested the T244A change counteracted the causative effect of the three FP changes on VCV resistance, we introduced it into the resistant triple FP mutant. 2012 Virology Discussion HIV T244A 78 83 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Here, we show that mutation-c, F519I, is an independent determinant of preference for the unoccupied high-affinity form of CCR5. 2012 Virology Discussion HIV F519I 31 36 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. In particular, three independent passage 9 clones contained one of the V3 substitutions T303A, F515L, or T317A in addition to the three FP changes (data not shown). 2012 Virology Discussion HIV F515L;T303A;T317A 95;88;105 100;93;110 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. In the other, three sequence changes (G516V, M518V and F519I) in the gp41 FP were sufficient for resistance. 2012 Virology Discussion HIV F519I;G516V;M518V 55;38;45 60;43;50 gp41 69 73 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Mutation-b (M518V), which has little or no effect on VCV sensitivity by itself, persisted throughout the reversion cultures, implying that there is no pressure for it to revert. 2012 Virology Discussion HIV M518V 12 17 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. No naturally occurring viruses in the HIV Sequence Database (http://www.hiv.lanl.gov/, updated as of 1/30/2012) contain all three FP changes, although some subtype B and C strains have the a+b (G516V+M518V) combination. 2012 Virology Discussion HIV G516V;M518V 194;200 199;205 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. On its own, but in a different genetic context, the T244A change drastically reduces virus entry. 2012 Virology Discussion HIV T244A 52 57 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Once it emerged, the T244A change persisted together with the 3FP changes. 2012 Virology Discussion HIV T244A 21 26 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. One involved at least an H308P change in V3 and either of the following combinations of gp41 changes: G514V+V535M or M518V+F519L+V535M. 2012 Virology Discussion HIV F519L;G514V;H308P;M518V;V535M;V535M 123;102;25;117;108;129 128;107;30;122;113;134 gp41 88 92 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The G516V change (mutation-a) by itself has been shown to confer CXCR4 usage on a clonal R5 virus. 2012 Virology Discussion HIV G516V 4 9 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. The resulting S+a,b,c+T244A virus was indeed VCV-sensitive in the PBMC-based, multi-cycle assay. 2012 Virology Discussion HIV T244A 22 27 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Together with several other changes scattered throughout Env, the G516V+M518V combination was also present in 8/12 clones at the time of virologic failure (compared to 0/12 at baseline) in a previously treatment-naive, subtype B-infected patient given the CCR5 inhibitor, aplaviroc, in combination with lopinavir-ritonavir. 2012 Virology Discussion HIV G516V;M518V 66;72 71;77 Env 57 60 22520838 Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance. Viruses resistant to VIRIP and its derivative VIR-353 contain a combination of three mutations in gp120 (A433T/V489I) and gp41 (V570I), but no changes in or near the FP. 2012 Virology Discussion HIV A433T;V489I;V570I 105;111;128 110;116;133 gp120;gp41 98;122 103;126 22530020 Counteraction of tetherin antiviral activity by two closely related SIVs differing by the presence of a Vpu gene. Interestingly, introduction of the W17C substitution in C. 2012 PloS one Discussion HIV W17C 35 39 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Although H221Y mutation alone just increases 2.1 ~ 3.6-fold resistance to NVP, the mutation could improve 100.6 ~ 3444.6-fold resistance to NVP when it copresent with Y181C. 2012 AIDS research and treatment Discussion HIV H221Y;Y181C;H221Y;Y181C 10;168;9;167 15;173;14;172 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. analyzed viruses from 13039 individuals with sequences containing at least one of 52 published NNRTI-selected mutations; the frequency of H221Y among 1510 viruses from individuals who received nevirapine but no other NNRTI was 12%. 2012 AIDS research and treatment Discussion HIV H221Y 138 143 NNRTI;NNRTI 95;217 100;222 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. As for residue 179, only V179F mutation did not decrease the susceptibility to etravirine; however, when the mutation combined with Y181C, the viral etravirine susceptibility could be reduced more than 100-fold. 2012 AIDS research and treatment Discussion HIV V179F;Y181C 25;132 30;137 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. As we have known, Y181C copresent with TAMs2 could increase the susceptibility to ZDV. 2012 AIDS research and treatment Discussion HIV Y181C 18 23 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. covered the virus containing K101E/Y181C/G190A and other mutations could increase 893-fold resistance to NVP. 2012 AIDS research and treatment Discussion HIV G190A;K101E;Y181C 41;29;35 46;34;40 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. described the resistant characters of 9 novel NNRTI-related mutations including K101Q, I135M/T, H221Y, K223E/Q, L228H/R, and V179I. 2012 AIDS research and treatment Discussion HIV H221Y;I135M;I135T;K101Q;K223E;K223Q;L228H;L228R;V179I 96;87;87;80;103;103;112;112;125 101;94;94;85;110;110;119;119;130 NNRTI 46 51 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. found that the occurrence of the H221Y was 19.8% in 91 patients receiving nevirapine and lamivudine plus stavudine (57.1%) or zidovudine (42.9%). 2012 AIDS research and treatment Discussion HIV H221Y 33 38 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. found the frequency of Y181C was 42.9% in the patients receiving NNRTI treatment for a median period of 53 weeks. 2012 AIDS research and treatment Discussion HIV Y181C 23 28 NNRTI 65 70 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. found the prevalence rate of H221Y in isolates from patients failing NVP treatment was 10.3% and the mutation was included in the top 10 and 15 determinants for NVP and EFV resistance, respectively, ranking even above some classical NNRTI resistance mutations, such as K101E, V108I, and G190E. 2012 AIDS research and treatment Discussion HIV G190E;H221Y;K101E;V108I 287;29;269;276 292;34;274;281 NNRTI 233 238 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. found the virus with K103N/Y181C and other mutations conferring above 1600-fold resistance to NVP, and Qari et al. 2012 AIDS research and treatment Discussion HIV K103N;Y181C 21;27 26;32 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. H221Y occurred along with Y181C in our study (data not shown) and the virus with mutation pattern K103N/Y181C/H221Y can replicate stably in vitro without drug pressure. 2012 AIDS research and treatment Discussion HIV H221Y;K103N;Y181C;Y181C;H221Y 110;98;104;26;0 115;103;109;31;5 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. H221Y was first reported related to NRTI treatment in 2003, but in recent study, H221Y was concerned associated with exposed to NNRTIs. 2012 AIDS research and treatment Discussion HIV H221Y;H221Y;H221Y;H221Y 2;82;81;0 6;87;86;5 NNRTI;NRTI 128;36 134;40 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. In our study, mutation patterns K101Q/H221Y, K101Q, V179D/H221Y, V179D, K103N/H221Y, and K103N, Y181C could, respectively, improve 759.1 +- 41.9, 1297.0 +- 289.1, 390.0 +- 101.6, 312.5 +- 45.3, 41.9 +- 8.4, and 47.9 +- 4.2-fold to NVP resistance. 2012 AIDS research and treatment Discussion HIV H221Y;H221Y;H221Y;K101Q;K101Q;K103N;K103N;V179D;V179D;Y181C 38;58;78;32;45;72;89;52;65;96 43;63;83;37;50;77;94;57;70;101 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. In previous study, the appearance of K101Q might be based on the occurrence of K103N. 2012 AIDS research and treatment Discussion HIV K101Q;K103N 37;79 42;84 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. In Reuman group's study, Y181C is the most common resistant mutation among the sequences from patients receiving NVP (48%), and nearly 17% (n = 2233) sequences contained three or more NNRTIs-resistant mutations and these NNRTIs-resistant profiles often carried Y181C and occurred with one or more thymidine analogue mutations, which suggested these mutation pattern might significantly associated with the function of HIV-1 RT. 2012 AIDS research and treatment Discussion HIV Y181C;Y181C 25;261 30;266 NNRTI;NNRTI;RT 184;221;424 190;227;426 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. In these novel mutations, K101Q and I135T copresented with K103N which related to the increase resistance of EFV and NVP. 2012 AIDS research and treatment Discussion HIV I135T;K101Q;K103N 36;26;59 41;31;64 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Many studies have reported the phenotype resistance of Y181C, Bacheler et al. 2012 AIDS research and treatment Discussion HIV Y181C 55 60 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Our study showed that as for the mutation profiles K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N, the presence of H221Y, respectively lead to 2.2 +- 0.9, 3.2 +- 0.3, 3.6 +- 0.5, 3.0 +- 0.4, 2.1 +- 0.5, and 2.2 +- 0.1-fold increase in NVP resistance. 2012 AIDS research and treatment Discussion HIV H221Y;K101Q;K101Q;K103N;K103N;V179D;V179D;Y181C;Y181C;Y181C 131;51;64;91;108;71;84;57;77;97 136;56;69;96;113;76;89;62;82;102 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Sungkanuparph group reported the prevalence rate of Y181C was 59.5% among the 158 NNRTI failure patients (for a median NNRTI treatment period of 88 weeks). 2012 AIDS research and treatment Discussion HIV Y181C 52 57 NNRTI;NNRTI 82;119 87;124 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. The group found H221Y was strongly associated with the use of NVP and showed positive interactions with Y181C and was also negatively associated with the use of ZDV and with TAMs (particularly TAMs-2, such as D67N, K70R, K219Q/E, and T215F) and was then associated with an increased susceptibility to ZDV. 2012 AIDS research and treatment Discussion HIV D67N;H221Y;K219E;K219Q;K70R;T215F;Y181C 209;16;221;221;215;234;104 213;21;228;228;219;239;109 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. The presence of H221Y along with Y181C was associated with a 12.4-fold increase in NVP resistance. 2012 AIDS research and treatment Discussion HIV H221Y;Y181C 16;33 21;38 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. To be specific, to K101Q, V179D, and K103N, Y181C/H221Y could confer 3444.6 +- 834.5, 1132.6 +- 180.4, and 100.6 +- 32.5-fold resistance to NVP. 2012 AIDS research and treatment Discussion HIV H221Y;K101Q;K103N;V179D;Y181C 50;19;37;26;44 55;24;42;31;49 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. When H221Y was copresent with TAMs-2, the ZDV susceptibility was even greater than that observed when TAMs-2 were copresent with Y181C. 2012 AIDS research and treatment Discussion HIV H221Y;Y181C 5;129 10;134 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Y181C is a very important NNRTIs-related drug resistant mutation, and the mutation can cause high-level resistance to NVP and DLV and low-level resistance to EFV; otherwise, this mutation can increase susceptibility to AZT and TDF. 2012 AIDS research and treatment Discussion HIV Y181C;Y181C 0;0 6;5 NNRTI 26 32 22536497 Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP. Y181C presents in 40% of patients failing NVP and has the third-greatest weight in the SVR (support vector regression) model for NVP resistance. 2012 AIDS research and treatment Discussion HIV Y181C 0 5 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Although the contribution of the new mutation dhps S436H (unreported prior to this study) to drug resistance is unclear, the mutations at dhfr 164 and dhps 581 or related genotypes have been associated with a high-level of SP resistance mainly in Southeast Asia and South America and, more recently, have been reported on the African continent. 2012 Malaria journal Discussion HIV S436H 51 56 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Recent data from Tanzania suggest that the emergence of the dhps triple mutant (A437G/K540E/A581G) associated with the IPTp-SP use in pregnant women led to high-density parasitaemia. 2012 Malaria journal Discussion HIV A437G;A581G;K540E 80;92;86 85;97;91 22540158 Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. This study also detected 5.3 % of the dhps triple mutant (A437G/K540E/A581G) (7 samples), the presence of quadruple dhps mutant (S436A/F/H + A437G + K540E + A581G) (1 sample), the dhfr 164 (I164L) mutation (1 sample), and an increase in the new mutation at dhps S436H (5 samples) in the third study period (2008-2009). 2012 Malaria journal Discussion HIV A437G;A581G;K540E;A437G;A581G;I164L;K540E;S436A;S436F;S436H;S436H 58;70;64;141;157;190;149;129;129;129;262 63;75;69;146;162;195;154;139;139;139;267 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. A methionine at position 255, found in one of the SF162 M48U1 resistant viruses, together with a S375N and L494V substitution presumably destabilizes and/or occluded the Phe43-cavity (Figure 5A). 2012 Retrovirology Discussion HIV L494V;S375N 107;97 112;102 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. A previous study reported a D474A mutant with nearly wild type affinity for CD4-Ig, but with a marked decrease in neutralization sensitivity. 2012 Retrovirology Discussion HIV D474A 28 33 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Also some cross-resistance towards the V3 mAb 447-52D was observed for all SF162 resistant viruses carrying the D474N mutation. 2012 Retrovirology Discussion HIV D474N 112 117 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. described a virus where a single S375N substitution conferred the virus resistant to a neutralizing human serum containing CD4bs antibodies and another group reported on this substitution in viruses resistant towards sCD4 and NBD-556, a small molecule that mimics CD4. 2012 Retrovirology Discussion HIV S375N 33 38 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Finally, the effect on entry was less pronounced for the viruses bearing the S375N, G471R, and D474N substitutions. 2012 Retrovirology Discussion HIV D474N;G471R;S375N 95;84;77 100;89;82 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Furthermore, only the BaL viruses resistant towards M48U1 showed wild type levels of sensitivity towards sCD4, consistent with data published about the S375W mutation, while the other viruses showed some cross-resistance. 2012 Retrovirology Discussion HIV S375W 152 157 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Furthermore, the pBRNL4.3 replication competent clone and the mutant pseudoviruses carrying D474N failed to reproduce the resistance observed with the SF162 resistant strains. 2012 Retrovirology Discussion HIV D474N 92 97 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Notably, the D474A mutation was also not detected in naturally occurring viruses (Los Alamos HIV-sequences database). 2012 Retrovirology Discussion HIV D474A 13 18 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Previously, a V255E substitution was shown to be responsible for in vitro selected sCD4 resistant viruses. 2012 Retrovirology Discussion HIV V255E 14 19 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Somewhat controversial data were collected for the D474N substitution. 2012 Retrovirology Discussion HIV D474N 51 56 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Surprisingly, a D474A substitution was previously shown to have a severe effect on viral infectivity in a BaL pseudovirus, but the same was not true for a YU-2 pseudovirus. 2012 Retrovirology Discussion HIV D474A 16 21 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Taken together, we do not have a valuable mechanistic explanation for this D474N resistant mutant to date. 2012 Retrovirology Discussion HIV D474N 75 80 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The histidine at position 105, highly conserved and part of the inner domain, was only found mutated in the M48 BaL resistant virus; but nevertheless H105Y conferred resistance, not only to M48, but also to M48U1 and sCD4. 2012 Retrovirology Discussion HIV H105Y 150 155 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The S375R substitution was responsible for a 67% reduction in entry efficiency. 2012 Retrovirology Discussion HIV S375R 4 9 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. The SF162 viruses resistant towards M48 and one of the SF162 viruses resistant against the combination of M48 and M48U1 (rCombiSF162_a) all selected for this D474N substitution as a single mutation. 2012 Retrovirology Discussion HIV D474N 158 163 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. This mutation was shown to decrease the entry efficiency into TZM-bl cells by 39%, but no significant differences were found in binding affinities for M48 and M48U1 towards the D474N mutant SF162 gp120 protein. 2012 Retrovirology Discussion HIV D474N 177 182 gp120 196 201 22551420 MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency. Two mutations resulted in a severe reduction in entry efficiency, with almost no infection observed for H105Y and V255M. 2012 Retrovirology Discussion HIV H105Y;V255M 104;114 109;119 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. Deep sequencing analyses of these transmitted viruses are ongoing to determine whether M184V transmissions continue but are missed by this assay or whether reversion to wild type after transmission is occurring. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 87 92 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. K103N is likely due to shifts in treatment regimens and its continued transmission could impact the use of first generation NNRTI agents as an initial treatment option in these individuals. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 0 5 NNRTI 124 129 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. Specific mutations and polymorphisms, such as K103N and L33F, have increased. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;L33F 46;56 51;60 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. The distribution of mutations is very similar to that reported in the European surveillance study SPREAD, with a predominance of the thymidine analog mutations, M41L and T215R/F, and L90M in the protease coding region. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV L90M;M41L;T215F;T215R 183;161;170;170 187;165;177;177 PR 195 203 22592583 Transmitted drug resistance and phylogenetic relationships among acute and early HIV-1-infected individuals in New York City. The transmission of M184V has steadily decreased since the 1990s. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 20 25 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. For example, I15V, a mutation highly prevalent in Chinese HIV-1+ patients who are drug users, appeared for the first time in 2007 with a prevalence of 9.5% (data not shown), doubled in 2008, and remained as one of the most common mutations for 2009 and 2010. 2012 AIDS research and treatment Discussion HIV I15V 13 17 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. K103N, the third most prevalent mutation for 2006 and the second most common mutation from 2007 to 2010, is frequently observed among nonnucleoside-RT-inhibitor-(NNRTI-) resistance mutations that neutralize efavirenz and nevirapine and has been identified as a prevalent mutation in other retrospective studies. 2012 AIDS research and treatment Discussion HIV K103N 0 5 NNRTI;RT 162;148 167;150 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. M36I, a mutation that allows faster in vitro HIV-1 replication regardless of the presence of protease inhibitors, was the second most common mutation for 2006. 2012 AIDS research and treatment Discussion HIV M36I 0 4 PR 93 101 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. M41L, the second most common mutation for 2006 and the third most common mutation for 2007, 2008, and 2010, is also a dominant NRTI-resistance mutation identified in the same studies. 2012 AIDS research and treatment Discussion HIV M41L 0 4 NRTI 127 131 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. Similarly, the protease resistance mutation L90M showed a divergent result between men and women in 2003, 2005, and 2006. 2012 AIDS research and treatment Discussion HIV L90M 44 48 PR 15 23 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. The reverse transcriptase mutation results indicate that M184V continues to be the most common mutation surveyed in our studies. 2012 AIDS research and treatment Discussion HIV M184V 57 62 RT 4 25 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. The statistically significant results for the reverse transcriptase mutation K70R have been noted for 2003 and 2006, while gender differences for K103N were observed in 2005 and 2007. 2012 AIDS research and treatment Discussion HIV K103N;K70R 146;77 151;81 RT 46 67 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. The third position was occupied by I13V in 2006, 2007, and 2009, while this place corresponded to I62V in 2008 and 2010. 2012 AIDS research and treatment Discussion HIV I13V;I62V 35;98 39;102 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. This is consistent with reports based on large-scale HIV-1 genotypic analyses that identify M184V/I as the most prevalent nucleoside and nucleotide-analog-RT-inhibitor- (NRTI-) resistance mutations that overcome the effects of drugs like emtricitabine and lamivudine. 2012 AIDS research and treatment Discussion HIV M184I;M184V 92;92 99;99 NRTI;RT 170;155 174;157 22593823 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010. V77I, a variant that has been identified as an important emerging substitution in HIV epidemiology studies, was the second most common mutation from 2007 to 2010. 2012 AIDS research and treatment Discussion HIV V77I 0 4 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Although UDPS has limitations particularly with regard to polymerization and pyrosequencing errors, recent studies with different methods (UDPS, allele specific PCR) have shown that K65R is identified more frequently in subtype C HIV-1 from naive patients. 2012 PloS one Discussion HIV K65R 182 186 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. As mentioned above, 2 isolates of the series exhibited a K65R substitution. 2012 PloS one Discussion HIV K65R 57 61 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. As noted above, the prevalence of K65R in this clinical context of failure ranges from 4 to 30%. 2012 PloS one Discussion HIV K65R 34 38 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. In our naive patients, there was a clear difference between K70R (mean 0%) and K65R (mean 0.66%) (Table 2). 2012 PloS one Discussion HIV K65R;K70R 79;60 83;64 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. In our series, we estimate this prevalence to be 8% and the UDPS data did not reveal any process of K65R selection that cannot be assessed by Sanger sequencing. 2012 PloS one Discussion HIV K65R 100 104 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. K65R substitutions are generated in subtype C isolates from naive patients due to the 64-65-66 motif. 2012 PloS one Discussion HIV K65R 0 4 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Our results are not in accordance with those obtained by another group using an allele- specific PCR which exhibited minority variants of K65R in four subtype C HIV-1 isolates out of 30 patients having received NRTIs at first line; it must be pointed out that this technique uses an intercalating dye and high-melt resolution assay which can be difficult to interpret due to genomic variability in the flanking region of codon 65. 2012 PloS one Discussion HIV K65R 138 142 NRTI 211 216 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Regarding the K65R values apart the two samples with K65R by Sanger, the UDPS quantities of K65R variants were low and below those of isolates from naive patients. 2012 PloS one Discussion HIV K65R;K65R;K65R 14;53;92 18;57;96 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. Second, there is an antagonism between TAMs and K65R, while the latter can be found in association with NAMs (Q151M) and is considered to be increasingly selected in the presence of DRMs to NNRTIs and particularly Y181C and G190A. 2012 PloS one Discussion HIV G190A;K65R;Q151M;Y181C 224;48;110;214 229;52;115;219 NNRTI 190 196 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. The Sanger results of isolates from treated patients were as expected with a predominance of M184V, numerous TAMs of pathway1 (M41L, D67N, K70R, L210W, T215Y/F) and DRMs to NNRTIs (mainly K101E, K103N, V106M, Y181C, G190A). 2012 PloS one Discussion HIV D67N;G190A;K101E;K103N;K70R;L210W;M184V;M41L;T215F;T215Y;V106M;Y181C 133;216;188;195;139;145;93;127;152;152;202;209 137;221;193;200;143;150;98;131;159;159;207;214 NNRTI 173 179 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. We hypothesize that these isolates are undergoing a process of selecting K70R mutations. 2012 PloS one Discussion HIV K70R 73 77 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. We were not expecting selection of K65R in this population of patients who were quite distant from primary infection and therefore from potential transmission of K65R mutants. 2012 PloS one Discussion HIV K65R;K65R 35;162 39;166 22615779 K65R in subtype C HIV-1 isolates from patients failing on a first-line regimen including d4T or AZT: comparison of Sanger and UDP sequencing data. With regard to UDPS results at codon 70, the quantitative data were different from those recorded in naive patients: 8 isolates exhibiting K70R with Sanger had UDPS K70R values above 34.60%, while 2 samples without K70R with Sanger (470 and 489) had K70R variants at quantities above the <0.4% background observed in naive patients. 2012 PloS one Discussion HIV K70R;K70R;K70R;K70R 139;165;215;250 143;169;219;254 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Additionally, the relatively small sample size does not allow for effective comparisons to be made with the concurrent d4T group and could be an explanation for why risk factors for K65R emergence could not be determined. 2012 AIDS (London, England) Discussion HIV K65R 182 186 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Although risk factors were not identified in this analysis, larger studies may reveal which patients could be at risk for developing K65R. 2012 AIDS (London, England) Discussion HIV K65R 133 137 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Although the M184V mutation may have emerged early, variants with this mutation would have been overcome by the more fit K65R variants which likely emerged later. 2012 AIDS (London, England) Discussion HIV K65R;M184V 121;13 125;18 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. During the initial ART rollout at McCord Hospital, the K65R mutation in patients failing first-line therapy for at least six months was reported in only three patients out of a total of 147 (2.6%). 2012 AIDS (London, England) Discussion HIV K65R 55 59 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. However, it is unlikely that a larger sample size would significantly alter the prevalence of the K65R mutation for patients receiving TDF and comparisons can be made with the historical reports of virologic failure and K65R for patients receiving d4T-containing ART in this same setting. 2012 AIDS (London, England) Discussion HIV K65R;K65R 98;220 102;224 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. However, mutations found in combination with K65R in our study either have a minor effect on susceptibility to AZT or enhance susceptibility to AZT (eg.L74V, Y181C, M184V as well as K65R). 2012 AIDS (London, England) Discussion HIV K65R;K65R;L74V;M184V;Y181C 45;182;152;165;158 49;186;156;170;163 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. In particular, RT of subtype C viruses may be especially prone to pausing events at codon 65 due to a poly-adenine region that allows for misalignment, misincorporation, strand transfer, insertions, deletions and recombinations, thereby facilitating the acquisition of K65R during reverse transcription. 2012 AIDS (London, England) Discussion HIV K65R 269 273 RT;RT 281;15 302;17 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. In this analysis, the findings of relatively fewer M184V mutations and absence of TAMs provides some evidence of the antagonism that exists between these mutations and K65R. 2012 AIDS (London, England) Discussion HIV K65R;M184V 168;51 172;56 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. K65R is uncommon among patients with subtype B who have received either tenofovir or a combination of tenofovir and emtricitabine as part of triple antiretroviral-drug therapy. 2012 AIDS (London, England) Discussion HIV K65R 0 4 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. K65R was also detected in 7 to 15% of patients in South Africa who did not have a response to first- or second-line regimens with d4T, ddI, or AZT as the nucleoside backbone. 2012 AIDS (London, England) Discussion HIV K65R 0 4 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Larger numbers of patients and longer follow-up are required to determine whether the emergence of K65R in subtype C is consistent and clinically relevant in this setting. 2012 AIDS (London, England) Discussion HIV K65R 99 103 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Of concern, HIV-1 from approximately 20% of patients in areas in which subtype C is endemic carries the K65R mutation, the K70E mutation, or both after experiencing VF of a d4T- or ddI-based ART regimen. 2012 AIDS (London, England) Discussion HIV K65R;K70E 104;123 108;127 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Recent data suggest that increased rates of K65R acquisition in subtype C may be due to the nature of the subtype C RNA template. 2012 AIDS (London, England) Discussion HIV K65R 44 48 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Some of the differences in these rates of acquisition of K65R or thymidine analog mutations (TAMs) are doubtless due to treatment regimens and disease stage, as well as limited access to viral-load testing in many developing countries. 2012 AIDS (London, England) Discussion HIV K65R 57 61 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. The data reported here show very high rates (>65%) of K65R for patients failing TDF-based first-line regimens at McCord with few additional NRTI mutations. 2012 AIDS (London, England) Discussion HIV K65R 54 58 NRTI 140 144 22739389 High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen. Ultrasensitive pyrosequencing methods have also shown that K65R can be selectively transmitted as minority species to some populations that have not yet received antiretroviral therapy. 2012 AIDS (London, England) Discussion HIV K65R 59 63 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. In two other cases K6L and B2R, we mis-positioned the insertion, and selected a downstream ATG (Table 2). 2012 PloS one Discussion HIV K6L 19 22 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Investigations of whether insertion at the authentic vaccinia virus ATG improves transgene expression at the K6L and B2R loci are currently on-going. 2012 PloS one Discussion HIV K6L 109 112 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. It is intriguing to speculate on the mechanism of deletion at the K6L and B2R loci in MVA (there is a repeated 9 bp or 5 bp sequence separated by 20 bp at these loci in vaccinia virus, which may be relevant) and on the potential selective advantage of the severe truncation of K6 and B2 during derivation of MVA by serial passage - especially given that there is an additional fragmenting deletion in the B2R region of MVA, and that these vaccinia virus genes are themselves fragments of larger ancestral ORFs found (for example) in cowpox virus. 2012 PloS one Discussion HIV K6L 66 69 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Nevertheless, either C11R or F11L transcripts are the most abundant by both methods; and A44L transcripts consistently the least abundant, with those of other ORFs targeted here generally occupying an intermediate position - including p7.5, which was analysed at its natural locus (WR001/C29L/B29R). 2012 PloS one Discussion HIV C29L;A44L;C11R;F11L 288;89;21;29 292;93;25;33 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Since we have not performed traditional growth curves, we cannot conclude that this difference in GFP kinetics necessarily represents enhanced growth, but this does not affect the conclusion, reached in combination with the yield data, that the growth of MVA expressing a pC11L-driven transgene in place of C11R is unimpaired. 2012 PloS one Discussion HIV C11R 307 311 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. The annotated initiation codons of MVA026L and MVA168R in the MVA genomic sequence (GenBank U94848.1) do not correspond to the authentic ATGs utilized in vaccinia virus K6L and B2R. 2012 PloS one Discussion HIV K6L 169 172 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. The two methods were not unanimous in the clustering of C11R, F11L, B8R and A44L into the IE (E1.1) or E (E1.2) classes (Table 1), and we could not detect any meaningful difference in protein expression at the earliest time point (Figure 3). 2012 PloS one Discussion HIV A44L;C11R;F11L 76;56;62 80;60;66 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. Two published approaches have enhanced the activity of early poxviral promoters: mutation of individual unfavourable nucleotides of the core region of the H5R promoter, known as mH5, and tandem insertion of multiple synthetic early promoter core regions, known as pHyb. 2012 PloS one Discussion HIV H5R 155 158 22761956 Expression and cellular immunogenicity of a transgenic antigen driven by endogenous poxviral early promoters at their authentic loci in MVA. We demonstrate this in MVA using the orthologs of C11R, F11L, B8R and A44L, and compared early protein expression and immunogenicity with that achievable using the traditional p7.5 or SSP promoters coupled to the transgenic ORF and inserted at the thymidine kinase locus. 2012 PloS one Discussion HIV A44L;C11R;F11L 70;50;56 74;54;60 22799593 Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model. This left just four peptides from conserved region two (C2) that were homologous between W61D and IIIB but heterologous for SF33. 2012 Retrovirology Discussion HIV W61D 89 93 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Also in the current study, withdrawal of tenofovir treatment did not lead to a detectable reversion from K65R to wild-type virus. 2012 Retrovirology Discussion HIV K65R 105 109 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Although we and others have previously described low or undetectable viremia after the emergence of K65R viral mutants in tenofovir-treated animals, the uniqueness of the present cohort of 5 animals resides in the unprecedented extensive period of tenofovir therapy (8 to 14 years) and survival. 2012 Retrovirology Discussion HIV K65R 100 104 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. As explained in more detail elsewhere, it is plausible that, whereas as no single factor may be sufficient, a synergistic combination of (i) effective antiviral immune responses, preserved by early initiation of treatment, and sustained by ongoing low-level replication of K65R virus, (ii) a minor effect of K65R and compensatory mutations on viral replication fitness or diversity, and (iii) some residual drug efficacy against K65R mutants was responsible for a steady-state situation without viral rebound in these tenofovir-treated animals. 2012 Retrovirology Discussion HIV K65R;K65R;K65R 273;308;429 277;312;433 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Despite the emergence of K65R viral mutants with 5-fold reduced in vitro susceptibility, all five animals had eventually reached undetectable viremia. 2012 Retrovirology Discussion HIV K65R 25 29 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. It has to be re-emphasized that this cohort of animals had unique circumstances, namely prolonged tenofovir monotherapy, started relatively early in infection, in the presence of K65R viral mutants resulting in the generation and maintenance of effective antiviral immune responses and creation of a relative steady-state balance. 2012 Retrovirology Discussion HIV K65R 179 183 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Previous experiments demonstrated that SIV and RT-SHIV isolates having the K65R mutation in combination with compensatory mutations have high replication fitness and virulence, and generally do not revert back to wild-type sequence following tenofovir withdrawal. 2012 Retrovirology Discussion HIV K65R 75 79 RT 47 49 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. The demonstration that a combination of tenofovir and antiviral immune responses can suppress K65R SIV replication in macaques for many years is also consistent with the lack of viral rebound in treatment-experienced patients who develop K65R viral mutants during tenofovir treatment, and the observations that viremia in persons with detectable K65R mutants can be suppressed by tenofovir-containing regimens. 2012 Retrovirology Discussion HIV K65R;K65R;K65R 94;238;346 98;242;350 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. The development and maintenance of the cellular and humoral immune responses we observed must have been promoted by ongoing low-level replication of K65R viral mutants during the prolonged period of tenofovir treatment which created a balanced antigen expression/immune response steady-state. 2012 Retrovirology Discussion HIV K65R 149 153 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. These animals were infected with virulent virus, and animals infected with these same viruses (wild-type or K65R) but not receiving any antiviral drug therapy were never able to spontaneously suppress viremia to low or undetectable levels and generally developed symptoms of AIDS within 2-24 months. 2012 Retrovirology Discussion HIV K65R 108 112 AIDS 275 279 22805180 Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. These observations suggest that the antiviral immune responses in these K65R virus-infected animals strengthened - rather than weakened- during the consecutive years of tenofovir treatment. 2012 Retrovirology Discussion HIV K65R 72 76 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. 5 are similar to those measured with H23C HIV-1 NC. 2013 Virus research Discussion HIV H23C 37 41 NC 48 50 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. Contrasting results were obtained when we replaced each of the aromatics by Ala, the mutations denoted F16A and W37A While the stretching and release curves in the presence of these aromatic substitution mutants continued to exhibit weak DNA duplex destabilization, significantly more hysteresis was observed, particularly at higher protein concentrations. 2013 Virus research Discussion HIV F16A;W37A 103;112 107;116 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. Finally, a mutant lacking both aromatic residues, F16A/W37A, induced significant hysteresis between DNA stretching and relaxation curves. 2013 Virus research Discussion HIV F16A;W37A 50;55 54;59 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. However, examination of reverse transcripts after infection of cells showed that the viral DNA that is made by Ala substitution mutants, especially W37A and F16A, W37A, could be a great deal more unstable. 2013 Virus research Discussion HIV F16A;W37A;W37A 157;148;163 161;152;167 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. The shape of the DNA stretching/relaxation curves in the presence of F16W and F16W/W37F HIV-1 NC are similar to that observed in the presence of WT NC, (compare. 2013 Virus research Discussion HIV F16W;F16W;W37F 69;78;83 73;82;87 NC;NC 94;148 96;150 22814429 Aromatic residue mutations reveal direct correlation between HIV-1 nucleocapsid protein's nucleic acid chaperone activity and retroviral replication. Therefore, our data suggest that F16W and F16W/W37F NC are still excellent nucleic acid chaperone proteins. 2013 Virus research Discussion HIV F16W;F16W;W37F 33;42;47 37;46;51 NC 52 54 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. It was also found that the D70A mutant, while showing lower binding to gp120 in both ELISA and SPR assays, showed better HIV inhibition than the other point mutants in some strains, again indicating a lack of direct correlation between binding to HIV gp120 and viral inhibition. 2012 Molecular pharmaceutics Discussion HIV D70A 27 31 gp120;gp120 71;251 76;256 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. These assays show a reduction in ability to bind gp120 from strain ADA, requiring concentrations about 10-fold higher from each mutant GRFT compared to the wild-type protein, with the D70A variant appearing to perform several fold worse than D30A or D112A. 2012 Molecular pharmaceutics Discussion HIV D112A;D30A;D70A 250;242;184 255;246;188 gp120 49 54 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. These experiments showed picomolar binding by wild-type GRFT and only a 2-3 fold reduction in binding by the point mutants D30A, D112A, and D70A, the latter showing slightly worse binding than the other two mutants. 2012 Molecular pharmaceutics Discussion HIV D112A;D30A;D70A 129;123;140 134;127;144 22827601 The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin. While this triple Asp-to-Asn mutant is likely quite similar to the triple D30A/D70A/D112A mutant reported here, we do see some minimal activity in D30A/D70A/D112A, while none has yet been reported for the Triple Asn construct. 2012 Molecular pharmaceutics Discussion HIV D112A;D112A;D30A;D30A;D70A;D70A 84;157;74;147;79;152 89;162;78;151;83;156 Asp 18 21 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Also in contrast to our results, studies with approximately 90% B subtype HIV-1 representation reported that N348I and A376S conferred varying degrees of nevirapine resistance, and that E399D conferred resistance to etravirine. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A376S;E399D;N348I 119;186;109 124;191;114 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Each of the other identified CD mutations (E399D, N348I, V365I, 318F, G333E, and A360V) was less than 10% prevalent. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A360V;E399D;G333E;N348I;V365I 81;43;70;50;57 86;48;75;55;62 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Further, K103N was seen primarily in CRF02_AG subtype and always with G335D in our cohort. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G335D;K103N 70;9 75;14 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Illustratively, polymorphic G335D or A371V in CRF01_AE subtype did not confer resistance by themselves, but there was increased ZDV resistance when either of these mutations was present with TAMs. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A371V;G335D 37;28 42;33 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. In another study, N3481, R356K, R358K, A360V and A371V were more frequently detected in ART-exposed compared with ART-naive subtype B patients. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A360V;A371V;R356K;R358K 39;49;25;32 44;54;30;37 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. In subtype B, CD mutations that have been associated with resistance include E312Q, G333E/D, G335D, N3481, A360I/V, V365I, T369I, A371V and A376S [6-9], but these associations are controversial; other investigators did not find a major detrimental effect of N3481, R356K, R358K, A360V or A371V on response to ART. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A360I;A360V;A360V;A371V;A371V;A376S;E312Q;G333D;G333E;G335D;R356K;R358K;T369I;V365I 107;107;279;130;288;140;77;84;84;93;265;272;123;116 114;114;284;135;293;145;82;91;91;98;270;277;128;121 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. In the current study, we found an association between presence of G335D and a tendency towards reduced risk of phenotypic etravirine or nevirapine resistance. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G335D 66 71 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. Our finding of a tendency towards reduced resistance to etravirine and nevirapine in the presence of G335D should be investigated further. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G335D 101 106 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. The K103N mutation does not cause etravirine resistance and it has been suggested that it may increase susceptibility to etravirine. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 4 9 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. This was demonstrated in the OPTIMA study (96.8% subtype B) where the frequencies of CD mutations in ART failures were A371V (21.4%), A376S (15.5%) and N348I (12.9%). 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A371V;A376S;N348I 119;134;152 124;139;157 22828721 Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity. We identified eight CD mutations, most commonly G335D (82.3%) and A371V (69.8%), among HIV-1 patients failing ART in Mali. 2012 Journal of acquired immune deficiency syndromes (1999) Discussion HIV A371V;G335D 66;48 71;53 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Among them, T39A, V179I, H208Y, K223E, L228H/R, R284K and V292I have been previously identified as secondary mutations associated with the accumulation of TAMs and with resistance to nucleoside analogues. 2012 Retrovirology Discussion HIV H208Y;K223E;L228H;L228R;R284K;T39A;V179I;V292I 25;32;39;39;48;12;18;58 30;37;46;46;53;16;23;63 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Despite differences in the catalytic parameters, nucleotide discrimination seems to play a minor role in the effects of R284K, since AZTTP and tenofovir-DP inhibition constants (Ki) were similar for both enzymes. 2012 Retrovirology Discussion HIV R284K 120 125 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Further evidence of this association was reported by a study of the Swiss Cohort that showed that the frequency of R284K increased from 1.1% in naive individuals to 5.1% in patients treated with thymidine analogues. 2012 Retrovirology Discussion HIV R284K 115 120 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. However, R284K increases the efficiency of the rescue reaction and facilitates the elongation of the unblocked primers. 2012 Retrovirology Discussion HIV R284K 9 14 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. However, the prevalence of R284K increased up to 4.1%, 6.5% and 9.3% in isolates having 2, 3 or 4 TAMs, respectively. 2012 Retrovirology Discussion HIV R284K 27 32 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In agreement with those findings, our cross-sectional study involving previously treated patients reveals that the presence of TAMs and M184V contributes to failure of salvage therapies containing the combination of tenofovir and emtricitabine, while K65R is relatively rare in those patients. 2012 Retrovirology Discussion HIV K65R;M184V 251;136 255;141 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In combination with TAM1 mutations, R284K produced 60-77% increase in the catalytic rate (kcat) for nucleotide incorporation. 2012 Retrovirology Discussion HIV R284K 36 41 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. In combination with TAMs, N348I and A360V decreased the efficiency of RNase H cleavage and increased excision of AZT in the presence of ATP. 2012 Retrovirology Discussion HIV A360V;N348I 36;26 41;31 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Interestingly, that analysis also showed that in those individuals exposed to thymidine analogues and didanosine, the frequency of R284K was 6.0%, while the frequencies of M41L, L210W, T215Y and M184V were 48.3%, 36.8%, 57.7% and 1.0%, respectively. 2012 Retrovirology Discussion HIV L210W;M184V;M41L;R284K;T215Y 178;195;172;131;185 183;200;176;136;190 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Interestingly, the differences in rescue efficiencies between M41L/L210W/T215Y/R284K and M41L/L210W/T215Y RTs were found with DNA/DNA template-primers, but not with RNA/DNA complexes. 2012 Retrovirology Discussion HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 67;94;62;89;79;73;100 72;99;66;93;84;78;105 RT 106 109 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Interestingly, the prevalence of R284K seems to increase with the exposure to nucleoside RT inhibitors. 2012 Retrovirology Discussion HIV R284K 33 38 RT 89 91 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. It has been suggested that secondary mutations such as E40F and K43E or L214F that associate with amino acid substitutions of the TAM1 resistance pathway could increase viral fitness by influencing the catalytic efficiency of the RT. 2012 Retrovirology Discussion HIV E40F;K43E;L214F 55;64;72 59;68;77 RT 230 232 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. It is also possible that the emergence of R284K in RTs having TAM1 mutations could have a negative impact on the stability of the viral RNA during reverse transcription, thereby explaining its small but significant reduction in viral fitness in the absence of inhibitors. 2012 Retrovirology Discussion HIV R284K 42 47 RT;RT 147;51 168;54 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K103N), since this drug had been co-administered with tenofovir/emtricitabine in 20.2% of the non-responding individuals. 2012 Retrovirology Discussion HIV K103N 0 5 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. K65R exerts an antagonistic effect on TAMs, by decreasing the ATP-mediated phosphorolytic activity that facilitates removal of NRTIs. 2012 Retrovirology Discussion HIV K65R 0 4 NRTI 127 132 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. On the other hand, L74V, V179I, K223E and L228H/R were previously identified as modulators of NNRTI resistance in a large study carried out in central Italy. 2012 Retrovirology Discussion HIV K223E;L228H;L228R;L74V;V179I 32;42;42;19;25 37;49;49;23;30 NNRTI 94 99 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Other mutations, such as the complex P272A/R277K/T286A and G333D had a minor effect on RNase H activity, but increased chain-terminated primer rescue with both RNA/DNA and DNA/DNA template-primers. 2012 Retrovirology Discussion HIV P272A;R277K;T286A;G333D 37;43;49;59 42;48;54;64 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Our biochemical studies showed that in the context of M41L/L210W/T215Y, the substitution of Lys for Arg284 has no effect on ATP-dependent excision. 2012 Retrovirology Discussion HIV L210W;M41L;T215Y;R284K 59;54;65;92 64;58;70;106 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Our results show that R284K has no effect on the viral susceptibility to thymidine analogues and tenofovir of isolates containing the TAM1 complex. 2012 Retrovirology Discussion HIV R284K 22 27 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Previous reports showed that the presence of three or more TAMs (particularly, M41L, T215Y and/or L210W) compromised the efficacy of tenofovir. 2012 Retrovirology Discussion HIV L210W;M41L;T215Y 98;79;85 103;83;90 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. RNase H assays carried out with both mutants and the wild-type RT revealed the higher endonucleolytic activity of M41L/L210W/T215Y/R284K RT in comparison with WT and mutant M41L/L210W/T215Y RTs. 2012 Retrovirology Discussion HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 119;178;114;173;131;125;184 124;183;118;177;136;130;189 RT;RT;RT 63;137;190 65;139;193 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. showed that the prevalence of R284K increased with the number of TAMs found in the viral genotype. 2012 Retrovirology Discussion HIV R284K 30 35 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Taken together, these results could explain why R284K confers a small fitness advantage in the presence of nucleoside analogues, as shown in the viral replication assays. 2012 Retrovirology Discussion HIV R284K 48 53 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The mechanism by which R284K confers a selective advantage in the context of TAM1 mutations is different from others previously described for mutations in the thumb-connection subdomains and in the RNase H domain. 2012 Retrovirology Discussion HIV R284K 23 28 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. The preservation of NNRTI mutations in the viral genome of treated patients can be attributed to their small effect on viral fitness, as demonstrated for V108I, Y181C and G190A. 2012 Retrovirology Discussion HIV G190A;V108I;Y181C 171;154;161 176;159;166 NNRTI 20 25 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Therefore, the minor differences in rescue efficiencies observed with AZTMP-, d4TMP- or tenofovir-terminated primers complexed with RNA could be explained by the poor stability of the template in rescue assays carried out with the M41L/L210W/T215Y/R284K mutant. 2012 Retrovirology Discussion HIV L210W;M41L;R284K;T215Y 236;231;248;242 241;235;253;247 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. These data together with the strong correlation of R284K and T215Y in our database suggest that the emergence of R284K is not related to the selection of the emtricitabine resistance mutation M184V. 2012 Retrovirology Discussion HIV M184V;R284K;R284K;T215Y 192;51;113;61 197;56;118;66 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. These results were also consistent with the low prevalence of K65R in the presence of TAMs, in patients receiving tenofovir-containing combination therapies. 2012 Retrovirology Discussion HIV K65R 62 66 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. This effect cannot be attributed to an influence on nucleic acid binding or processivity but to the higher catalytic efficiency of the M41L/L210W/T215Y/R284K RT in comparison with the M41L/L210W/T215Y enzyme. 2012 Retrovirology Discussion HIV L210W;L210W;M41L;M41L;R284K;T215Y;T215Y 140;189;135;184;152;146;195 145;194;139;188;157;151;200 RT 158 160 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. This effect was also consistent with the higher efficiencies of primer extension observed with the M41L/L210W/T215Y/R284K RT, using different concentrations of template-primer. 2012 Retrovirology Discussion HIV L210W;M41L;R284K;T215Y 104;99;116;110 109;103;121;115 RT 122 124 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Thus, mutations such as N348I, A360V and Q509L increased chain-terminated primer rescue with RNA/DNA complexes, but not with DNA/DNA template-primers. 2012 Retrovirology Discussion HIV A360V;N348I;Q509L 31;24;41 36;29;46 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Thus, TAM1 includes the amino acid substitutions M41L, L210W and T215Y, while TAM2 contains mutations D67N, K70R, K219E/Q and sometimes T215F. 2012 Retrovirology Discussion HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 102;114;114;108;55;49;136;65 106;121;121;112;60;53;141;70 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. V118I and M184V are mutations selected under therapy with lamivudine (reviewed in refs.), while V179I has been associated with resistance to NNRTIs. 2012 Retrovirology Discussion HIV M184V;V179I;V118I 10;96;0 15;101;5 NNRTI 141 147 22889300 Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. V118I, V179I, M184V and R284K appear to be associated with the TAM1 pathway. 2012 Retrovirology Discussion HIV M184V;R284K;V179I;V118I 14;24;7;0 19;29;12;5 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Data from our single nucleotide extension assays show that while WT and Lys66Arg are efficient in extending from a mismatched primer terminus, the non-conservative mutants show 5-6-fold reduction in mismatch extension efficiency (fext). 2012 The FEBS journal Discussion HIV K66R 72 80 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. In addition, Lys65Arg has also been identified as the primary mutation selected for by Tenofovir (TFV) and has been shown to confer cross-resistance to other inhibitors including d4T in both cell-based and cell-free assays. 2012 The FEBS journal Discussion HIV K65R 13 21 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Interestingly, although the enzymes in complexes at -17 are positioned such that they can readily accept an incoming nucleotide, this increase in post-translocation complexes does not correlate with an increase in extension from a mismatched t/p for Lys66Ala, Asn and Thr. 2012 The FEBS journal Discussion HIV K66A 250 258 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. Several substitutions at residues that do not directly line the active site, but yet impinge upon it via interaction with template or primer, such as Met230Ile (in the primer grip) and Glu89Gly (at -2 position on the template) have also been shown to bring about increases in fidelity. 2012 The FEBS journal Discussion HIV E89G;M230I 185;150 193;159 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. The extent to which the enzyme is found in a -19(-2) additional pre-translocation position differs significantly for WT and the Lys66Ala, Asn and Thr (Figure 5C, Right panel). 2012 The FEBS journal Discussion HIV K66A 128 136 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. The Lys66Arg substitution did not alter the misinsertion fidelity, while the non-conservative mutants showed a reduced ability to misinsert. 2012 The FEBS journal Discussion HIV K66R 4 12 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. This discrepancy between t/p positioning and mismatch extension efficiency was also described previously for a Lys65Ala mutant. 2012 The FEBS journal Discussion HIV K65A 111 119 22925131 Lys66 residue as a determinant of high mismatch extension and misinsertion rates of HIV-1 reverse transcriptase. While the Lys65Arg mutation has been widely studied in drug resistance, the drug resistance effects of mutations at position 66 have not been tested. 2012 The FEBS journal Discussion HIV K65R 10 18 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. According to Mutation ARV Evidence Listing (MARVEL), V106M appeared in 14% NNRTI treated patients with subtype C HIV infection, whereas it was found in only 0.5% of the treated patients carrying subtype B virus. 2012 PloS one Discussion HIV V106M 53 58 NNRTI 75 80 HIV infections 113 126 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. As shown in MARVEL, the prevalence of the other major mutation Y181C in NNRTI treated patients with subtype B and C virus are 21% and 12%, respectively. 2012 PloS one Discussion HIV Y181C 63 68 NNRTI 72 77 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. CRF07_BC may inherit V106M development preference from subtype C by NNRTI treatment. 2012 PloS one Discussion HIV V106M 21 26 NNRTI 68 73 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. For example, V108I has been reported to correlate with the appearance of Y181C in the patients or in cell culture as an accessory mutation and it also recurred in the present study. 2012 PloS one Discussion HIV V108I;Y181C 13;73 18;78 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. In previous in vitro studies, both Y181C and V106A have been reported as initial mutations resistant to NVP in both subtype B and C viruses, but V106A was not an initial mutation selected by NVP treatment in this study. 2012 PloS one Discussion HIV V106A;V106A;Y181C 45;145;35 50;150;40 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. In the present study, Y181C was developed in one of five parallel cultures, suggesting that this major drug resistant mutation would also appear in patients infected with CRF07_BC virus after receiving NVP therapy. 2012 PloS one Discussion HIV Y181C 22 27 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. In this study, V106M developed in three out of five parallel cultures. 2012 PloS one Discussion HIV V106M 15 20 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Initial mutations A98G, V108I and Y181C appeared during the first 10 passages in the presence of 800 nM NVP (4-fold of EC50), while double mutations I135T/I382L were detected between passages 10 and 15 (Figure 4). 2012 PloS one Discussion HIV A98G;I135T;I382L;V108I;Y181C 18;149;155;24;34 22;154;160;29;39 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Interestingly, V106M development bias was only found under EFV but not NVP treatment in the previous studies and there was no significant difference of V106M prevalence between subtype B and C in patients receiving NVP treatment. 2012 PloS one Discussion HIV V106M;V106M 15;152 20;157 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. It seemed that V106M were inclined to develop in subtype C virus. 2012 PloS one Discussion HIV V106M 15 20 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Our results also showed that V106M was likely to accumulate with I178M in CRF07_BC. 2012 PloS one Discussion HIV I178M;V106M 65;29 70;34 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Polymorphisms at position 4, 48, 135, 178 of RT have been reported in CRF07_BC in China but only I135T was found in treatment naive patients with CRF07_BC infection. 2012 PloS one Discussion HIV I135T 97 102 RT 45 47 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Similarly, V108I has been found in both subtype B and C viruses, whereas A98S was only detected in subtype C virus. 2012 PloS one Discussion HIV A98S;V108I 73;11 77;16 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. The low mutation barrier at these positions suggests that A98G, V108I and Y181C may be found in NVP treated patients infected with CRF07_BC with high possibility. 2012 PloS one Discussion HIV A98G;V108I;Y181C 58;64;74 62;69;79 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. The other two mutations, A98G and V108I, have been reported to be polymorphic accessory mutations in patients with subtype B or C virus, while K238N is rarely selected by NNRTI and not common to be found in NNRTI-treated patients with infection of subtype B or C virus (prevalence<0.5%). 2012 PloS one Discussion HIV A98G;K238N;V108I 25;143;34 29;148;39 NNRTI;NNRTI 171;207 176;212 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. The results have also suggested that major NNRTI mutations Y181C and V106M may be found in patients harboring CRF07_BC virus with high possibility when NVP was included in ART treatment and these two mutations may cause serious resistance to not only NVP but also other NNRTI. 2012 PloS one Discussion HIV V106M;Y181C 69;59 74;64 NNRTI;NNRTI 43;270 48;275 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. This indicated that both subtype B and C viruses were likely to develop Y181C after receiving NNRTI treatment. 2012 PloS one Discussion HIV Y181C 72 77 NNRTI 94 99 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Thus far, about 32 NVP-resistance associated mutations in 17 positions, including 15 major NVP-resistant mutations at 5 positions (K103NST, V106AM, Y181CIV, Y188LHC, G190ASEQ), have been summarized in HIV drug resistance database of Stanford University. 2012 PloS one Discussion HIV G190A;G190E;G190Q;G190S;K103N;K103S;K103T;V106A;V106M;Y181C;Y181I;Y181V;Y188C;Y188H;Y188L 166;166;166;166;131;131;131;140;140;148;148;148;157;157;157 174;174;174;174;138;138;138;146;146;155;155;155;164;164;164 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Two mutations, V106M and Y181C, have been reported to be major drug resistant mutations. 2012 PloS one Discussion HIV V106M;Y181C 15;25 20;30 22984494 Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. Y181C, K103N, G190A, H221Y, K101E, A98G, V108I, V106A, E138A, Y188L are the top ten most common mutations resistant to NVP in patients who received NVP treatment. 2012 PloS one Discussion HIV A98G;E138A;G190A;H221Y;K101E;K103N;V106A;V108I;Y188L;Y181C 35;55;14;21;28;7;48;41;62;0 39;60;19;26;33;12;53;46;67;5 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Finally, the combination of E92Q+N155H produces robust resistance to both raltegravir and elvitegravir in HIV-2, providing a third pathway to high-level resistance. 2012 PloS one Discussion HIV E92Q;N155H 28;33 32;38 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. In contrast, the Y143C change had little or no effect on raltegravir susceptibility; robust resistance to the drug required the addition of E92Q together with Y143C. 2012 PloS one Discussion HIV E92Q;Y143C;Y143C 140;17;159 144;22;164 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. In the case of raltegravir, high-level resistance requires the combination of E92Q+Y143C, whereas T97A+Y143C is required for robust elvitegravir resistance. 2012 PloS one Discussion HIV E92Q;T97A;Y143C;Y143C 78;98;83;103 82;102;88;108 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Specifically, Ni and colleagues used a cell-free strand transfer assay to demonstrate that substitutions G140S+Q148R and N155H in HIV-2 integrase confer moderate to high-level resistance to raltegravir. 2012 PloS one Discussion HIV G140S;N155H;Q148R 105;121;111 110;126;116 IN 136 145 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. The first is centered around Y143C, which alone has only a modest effect on drug susceptibility. 2012 PloS one Discussion HIV Y143C 29 34 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. The second pathway is defined by G140S+Q148R, which yields high-level resistance to both drugs. 2012 PloS one Discussion HIV G140S;Q148R 33;39 38;44 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. Thus, while E92Q and G140S alone had no significant impact on raltegravir sensitivity, these replacements cooperated with Y143C and Q148R, respectively, to impart high-level raltegravir resistance in the strand transfer assay. 2012 PloS one Discussion HIV E92Q;G140S;Q148R;Y143C 12;21;132;122 16;26;137;127 23028968 Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. While Q148R alone is sufficient for a dramatic loss of elvitegravir sensitivity, our data show that G140S cooperates with Q148R to restore replication capacity, and will therefore likely enhance viral fitness and escape in both raltegravir- and elvitegravir-treated HIV-2 patients. 2012 PloS one Discussion HIV G140S;Q148R;Q148R 100;6;122 105;11;127 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. Accumulation of the other mutations observed included thymidine associated mutations (including M41L, D67N, K70R, L210W, T215Y/F, K219Q) results in increasing resistance to AZT, Tenofovir, D4T, Abacavir, and DDI . 2012 Diagnostic pathology Discussion HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 102;130;108;114;96;121;121 106;135;112;119;100;128;128 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. Concerning first-line ART failures, 38% of 16 strains sequenced in this group had the M184V mutation. 2012 Diagnostic pathology Discussion HIV M184V 86 91 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. Patients receiving incompletely suppressive 3TC regimens usually develop M184V as their first mutation . 2012 Diagnostic pathology Discussion HIV M184V 73 78 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. The NNRTI resistance-conferring mutations included K103N (25%), Y188L (12.5%), Y181C (6%), G190A (6%), H221Y (6%), M230L (6%). 2012 Diagnostic pathology Discussion HIV G190A;H221Y;K103N;M230L;Y181C;Y188L 91;103;51;115;79;64 96;108;56;120;84;69 NNRTI 4 9 23044036 HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients. The T215Y mutation was observed in 13% of the sequences while T215F was detected in 6%. 2012 Diagnostic pathology Discussion HIV T215F;T215Y 62;4 67;9 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Although some researchers characterize D67N as a TAM-2 pathway mutation, this change has also been found in a TAM-1 background, in agreement with our data. 2012 PloS one Discussion HIV D67N 39 43 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Clone RTB started accumulating the mutation Q151M right after rebounding and this change was retained all over the culture. 2012 PloS one Discussion HIV Q151M 44 49 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Furthermore, an additional mutation, D67N, was incorporated when the VL rebounded to original levels comparable to those before the onset of drug selection (figure 1B). 2012 PloS one Discussion HIV D67N 37 41 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. However, in some replicates, this shifting was incomplete and a mixture M184M/I/V was present at the end of the selection process. 2012 PloS one Discussion HIV M184I;M184M;M184V 72;72;72 81;81;81 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. However, RTC and RTC' data suggest that D67N and K70R were selected instead of T215F and then directed to TAM-2. 2012 PloS one Discussion HIV D67N;K70R;T215F 40;49;79 44;53;84 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. However, three different final profiles with D67N and K70R mutations were observed in all replicates: T215I or T215F or T215F/I. 2012 PloS one Discussion HIV D67N;K70R;T215F;T215F;T215I;T215I 45;54;111;120;120;102 49;58;116;127;127;107 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. In addition, given that D67N does not impact on replicative capacity, this mutation could be selected first and then be replaced by T215Y, which has a major impact on ZDV resistance. 2012 PloS one Discussion HIV D67N;T215Y 24;132 28;137 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. In addition, RTC' appears to select M184V faster than RTB' (Table 2), which is in accordance with previous reports. 2012 PloS one Discussion HIV M184V 36 41 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Interestingly, no secondary mutation of Q151M-MNR was significantly evident upon selection with ZDV when the mutation Q151M was selected (RTB). 2012 PloS one Discussion HIV Q151M;Q151M 40;118 45;123 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Interestingly, the recombinant virus carrying RTC followed a different route and initially accumulated D67N before rebounding and added K70R during the rebound process. 2012 PloS one Discussion HIV D67N;K70R 103;136 107;140 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Moreover M184V brings an advantage for management of the treatment because the M184V-containing enzyme is less processive, decreasing the error of RT and consequently the frequency of mutations throughout the viral genome. 2012 PloS one Discussion HIV M184V;M184V 9;79 14;84 RT 147 149 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Moreover, D67N could help to enhance RT processivity when selected after T215Y. 2012 PloS one Discussion HIV D67N;T215Y 10;73 14;78 RT 37 39 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Nevertheless, both clones behaved similarly when the same selection (M184I) was obtained using 3TC (figure 1A). 2012 PloS one Discussion HIV M184I 69 74 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Nevertheless, M184V has a major impact in both 3TC resistance and RT processivity. 2012 PloS one Discussion HIV M184V 14 19 RT 66 68 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. One of the RTC' replicates treated with 3TC selected the E203K mutation (Table 2). 2012 PloS one Discussion HIV E203K 57 62 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Our study has shown that both RTB' and RTC' treated with 3TC selected M184I in 8 weeks, but when selection continues until higher 3TC concentrations, we observed a shift from M184I to M184V (primary mutations). 2012 PloS one Discussion HIV M184I;M184I;M184V 70;175;184 75;180;189 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Probably T215I has less impact on replicative capacity than T215F. 2012 PloS one Discussion HIV T215F;T215I 60;9 65;14 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Q151M is a primary mutation that in vivo can be co-selected together with a group of secondary mutations (A62V, V75I, F77L and F116Y) that confers a cross-resistance with all NRTIs. 2012 PloS one Discussion HIV A62V;F116Y;F77L;V75I;Q151M 106;127;118;112;0 110;132;122;116;5 NRTI 175 180 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Similarly our RTB' data show that T215Y was the first mutation detected in TAM-1 pathway. 2012 PloS one Discussion HIV T215Y 34 39 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Some replicates initiated selection with T215F and others with the D67N and K70R mutations. 2012 PloS one Discussion HIV D67N;K70R;T215F 67;76;41 71;80;46 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Sturmer M (2004), Ceccherini-Silberstein (2007) and F Puertas MC (2009) observed a negative association of F214L and T215Y, which was related to a decrease in replicative capacity and resistance if compared with viruses carrying only T215Y. 2012 PloS one Discussion HIV F214L;T215Y;T215Y 107;117;234 112;122;239 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The additional selection experiments done in sextuplicate with RTB' selected the T215Y TAM-1 pathway in all cases associated with F214L and D67N (Table 3). 2012 PloS one Discussion HIV D67N;F214L;T215Y 140;130;81 144;135;86 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. The mutation D67N was replaced by T215I after the virus reached a VL value comparable to the levels before the onset of selection (figure 1B). 2012 PloS one Discussion HIV D67N;T215I 13;34 17;39 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. They also showed that the TAM-2 mutant D67N/K70R/T215F had the slowest replication levels between both subtypes. 2012 PloS one Discussion HIV D67N;K70R;T215F 39;44;49 43;48;54 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. This change, alongside with other mutations (K43E/N/Q, H208Y, and D218E), have already been associated with NRTI resistance; however, its actual impact in NRTI resistance has not been yet characterized. 2012 PloS one Discussion HIV D218E;H208Y;K43E;K43N;K43Q 66;55;45;45;45 71;60;53;53;53 NRTI;NRTI 108;155 112;159 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. This complex, located around the catalytic site of the RT, is commonly referred to as "Q151M-mediated multinucleoside resistance" (Q151M-MNR). 2012 PloS one Discussion HIV Q151M;Q151M 87;131 92;136 RT 55 57 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. This might explain why D67N and K70R emerged first and then T215I was selected instead of 215F in 66% of replicates. 2012 PloS one Discussion HIV D67N;K70R;T215I 23;32;60 27;36;65 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. This switch from isoleucine to valine could be due to the fact that M184I has a minor impact in RT processivity despite conferring 3TC resistance. 2012 PloS one Discussion HIV M184I 68 73 RT 96 98 23056372 Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C. Whereas T215Y is one of the TAM-1 mutations firstly selected, that is not the case for T215F in the TAM-2 pathway. 2012 PloS one Discussion HIV T215F;T215Y 87;8 92;13 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. confirmed enhanced ETR resistance for N348I with NNRTI-containing POLs. 2013 Virology Discussion HIV N348I 38 43 NNRTI;Pol 49;66 54;70 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Furthermore, CN mutation E399D was also found to be associated with ETR resistance, and T386A CN mutation was selected for ETR resistance during in vitro selection studies. 2013 Virology Discussion HIV E399D;T386A 25;88 30;93 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. recently reported that N348I was significantly increased in subtype-C-infected patients failing therapy, and was associated with enhanced resistance to EFV, NVP, ETR and AZT. 2013 Virology Discussion HIV N348I 23 28 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. showed that N348I increases resistance across different subtypes and increases ETV (~2 fold), NVP (~5 fold) and EFV (~3-5 fold) resistance, Furthermore, it was shown that N348I may be selected in the presence of NVP or EFV drug therapy. 2013 Virology Discussion HIV N348I;N348I 12;171 17;176 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Stanford University HIV Drug Resistance Database analysis confirmed that three of the identified CN mutations, G335E, N348I and A371V were positively associated with subtype-C treatment-experienced patients. 2013 Virology Discussion HIV A371V;G335E;N348I 128;111;118 133;116;123 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. The mutations observed with our subtype-C cohort, A376S, A400T, Q334D, G335D, N348I, and A371V, were similar to those previously reported for subtype B. 2013 Virology Discussion HIV A371V;A376S;A400T;G335D;N348I;Q334D 89;50;57;71;78;64 94;55;62;76;83;69 23068886 Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. which showed enhanced ETR resistance with CN mutations T369I and N348I in the presence of specific NNRTI-containing POL domains. 2013 Virology Discussion HIV N348I;T369I 65;55 70;60 NNRTI;Pol 99;116 104;119 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. However, tenofovir is also associated with an increased frequency of the mutation K65R. 2013 AIDS (London, England) Discussion HIV K65R 82 86 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. In vitro studies suggest that K65R develops more readily in subtype C because of a site specific pause on the viral template during transcription and this same mechanism may occur for subtypes found in Nigeria. 2013 AIDS (London, England) Discussion HIV K65R 30 34 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. K65R is selected by tenofovir, didanosine, stavudine and abacavir, but it may be emerging at higher frequencies among non-B subtypes exposed to TDF. 2013 AIDS (London, England) Discussion HIV K65R 0 4 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. M184I (7/23) and Y115F (3/23), are relatively uncommon mutations but occurred more often for those on tenofovir. 2013 AIDS (London, England) Discussion HIV Y115F;M184I 17;0 22;5 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. M184V was the most frequent mutation among TDF based regimens and the only one associated with a lower mean HIV-1 RNA viral load. 2013 AIDS (London, England) Discussion HIV M184V 0 5 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Only 12% of patients with the K65R mutation developed TAMs compared with 70% of those without the K65R mutation. 2013 AIDS (London, England) Discussion HIV K65R;K65R 30;98 34;102 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Other studies have shown there is an antagonistic relationship between TAMs and K65R. 2013 AIDS (London, England) Discussion HIV K65R 80 84 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Prior studies have shown that the TAM 2 pathway has lower levels of TDF resistance, increased sensitivity to AZT with M184V, and slower rates of TAM acquisition. 2013 AIDS (London, England) Discussion HIV M184V 118 123 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Similar prevalences of K65R in TDF based regimens were reported by other studies of non-B subtypes. 2013 AIDS (London, England) Discussion HIV K65R 23 27 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Tenofovir is partially active and it is enhanced when K65R co-occurs with M184V. 2013 AIDS (London, England) Discussion HIV K65R;M184V 54;74 58;79 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. The M184I may eventually switch to M184V and Y115F may be increasing for those on tenofovir, but the small numbers limit our inferences. 2013 AIDS (London, England) Discussion HIV M184I;M184V;Y115F 4;35;45 9;40;50 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Viruses with M184V have a decreased replicative capacity and its presence may suggest adherence. 2013 AIDS (London, England) Discussion HIV M184V 13 18 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. We report 57% of patients (13/23) on TDF based regimens had K65R, a relatively uncommon mutation (1.7-4%) in viruses of subtype B. 2013 AIDS (London, England) Discussion HIV K65R 60 64 23079810 Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. Zidovudine and stavudine remain fully active with K65R, but abacavir and didanosine have reduced activity. 2013 AIDS (London, England) Discussion HIV K65R 50 54 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. A combination of V106I and V179D has been shown to confer significant resistance to efavirenz . 2012 BMC research notes Discussion HIV V106I;V179D 17;27 22;32 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. Among TASER-M patients, only 1 had a combination of V106I and V179D. 2012 BMC research notes Discussion HIV V106I;V179D 52;62 57;67 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. Only 2 patients had a combination of K103R and V179D. 2012 BMC research notes Discussion HIV K103R;V179D 37;47 42;52 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. The 5-level Stanford HIVdb predicted "potential low-level resistance" in all sequences with discordant efavirenz interpretation containing V179D/E. 2012 BMC research notes Discussion HIV V179D;V179E 139;139 146;146 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. The RAMs associated with efavirenz discrepancy were V179D/E. 2012 BMC research notes Discussion HIV V179D;V179E 52;52 59;59 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. Therefore, the significance of V179D/E found in this study should not be interpreted as the cause of the differences between the two interpreting systems, but merely reflects the mutation pattern based on the Stanford HIVDR list. 2012 BMC research notes Discussion HIV V179D;V179E 31;31 38;38 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. V179D also confers significant resistance to NNRTIs when presented together with K103R . 2012 BMC research notes Discussion HIV K103R;V179D 81;0 86;5 NNRTI 45 51 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. V179D is associated with low-level resistance to NNRTIs and is considered to have no significant effect on the efficacy of NNRTI-containing regimen. 2012 BMC research notes Discussion HIV V179D 0 5 NNRTI;NNRTI 49;123 55;128 23095645 Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis. V179D/E are often found in treatment-naive individuals infected with non-B subtypes . 2012 BMC research notes Discussion HIV V179D;V179E 0;0 7;7 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. First, the T242N mutation affects the viral replication through interacting with cyclophilin A . 2012 Retrovirology Discussion HIV T242N 11 16 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. However, analysis of 51 SGA sequences did not show the reversion mutation (I64T) after the T/F virus was passaged six times. 2012 Retrovirology Discussion HIV I64T 75 79 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. However, the fitness loss by the T242N mutation was clearly demonstrated when the cell free viruses were passaged multiple times as shown in this study and a previous report . 2012 Retrovirology Discussion HIV T242N 33 38 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. In addition, analysis of over 2000 viral genomes from the co-culture of the NIA and T242N viruses (both with the T242N mutation) at passage 4 did not show the wild type base at position 242. 2012 Retrovirology Discussion HIV T242N;T242N 84;113 89;118 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. In two comparison pairs (T/F verses T242N and NIA verses T242T), no difference in replication rates were observed for the compared viruses in the single passage assay even though the viruses increased exponentially in the cell culture medium. 2012 Retrovirology Discussion HIV T242N;T242T 36;57 41;62 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Interestingly, all three recombinants (V247I, I64T and R355K) detected in vitro in this study were also identified in vivo (Figure 1A and 1C), suggesting that those recombinant viruses are naturally present in HIV-1-infected individuals. 2012 Retrovirology Discussion HIV I64T;R355K;V247I 46;55;39 50;60;44 HIV infections 211 225 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Since the viral entry was not impaired by the T242N mutation, the T242N was marginally less fit than T/F in the single passage assay. 2012 Retrovirology Discussion HIV T242N;T242N 46;66 51;71 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Since V247I was a reversion mutation, the emergence and domination of this virus suggest that it is also more fit than the T/F virus in vivo although this still needs to be experimentally confirmed. 2012 Retrovirology Discussion HIV V247I 6 11 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The accumulation of more fit viruses with V247I mutation can also readily compensate the fitness cost of the T242N mutation when it is selected later. 2012 Retrovirology Discussion HIV T242N;V247I 109;42 114;47 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The CTL escape mutation T242N alone had a significant fitness cost as previously shown by others . 2012 Retrovirology Discussion HIV T242N 24 29 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The p24 concentration of T242N was only less than two fold lower than that of the wt or T/F virus at the end of the culture when virus replication plateaued as shown in a previous study and by our result (Figure 2B). 2012 Retrovirology Discussion HIV T242N 25 30 p24 4 7 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The TK virus with both the I64T mutation in Tat/Rev and the R355K CTL escape mutations in Env represent a naturally selected virus in vivo. 2012 Retrovirology Discussion HIV I64T;R355K 27;60 31;65 Rev;Tat;Env 48;44;90 51;47;93 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. The V247I virus was detected as the predominant virus before the CTL escape mutation T242N was detected and then fixed together with the T242N mutation in the viral population. 2012 Retrovirology Discussion HIV T242N;T242N;V247I 85;137;4 90;142;9 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. This is in good agreement with the in vivo observations, in which the T242N mutation reverted back to the wild type base after months of infection . 2012 Retrovirology Discussion HIV T242N 70 75 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Two other recombinants (viruses with either I64T or R355K mutation) were only detected in vivo at low frequencies shortly after infection and then quickly replaced by the TK virus (Figure 1C), suggesting they are less fit in vivo under selection pressure. 2012 Retrovirology Discussion HIV I64T;R355K 44;52 48;57 23110705 Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. We determined the fitness cost of two CTL escape mutations (R355K in Env and T242N in Gag) in the context of other mutations in the cognate viral genomes (TK and NIA, respectively). 2012 Retrovirology Discussion HIV R355K;T242N 60;77 66;82 Env;Gag 69;86 72;89 23140174 CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90. Also, protein phosphatase M1A (PPM1A) was recently shown to dephosphorylate CDK9 on Thr186 in cultured cells. 2012 Retrovirology Discussion HIV M1A 26 29 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Although the mutation at 369 position appeared inconsequential, namely T369A at the first codon (ACA GCA) and T369V at the first two codon(ACA GTA), the impact on drug susceptibility was great. 2012 PloS one Discussion HIV T369A;T369V 71;110 76;115 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Brehm et al also reported in 2007 that mutation A371V at the connection domain could enhance the resistance level to AZT along with TAMs. 2012 PloS one Discussion HIV A371V 48 53 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. In addition, mutations K336R and I375V at the connection domain could promote the replication fitness of virus pNL4-3 under AZT and EFV exposure, relative to pNL4-3wild. 2012 PloS one Discussion HIV I375V;K336R 33;23 38;28 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Interestingly, mutation at position 369 of RT for variation T369A could enhance the susceptibility of virus to AZT and EFV, but the variation T369V resulted in resistance to AZT, EFV and NVP, a finding not reported previously. 2012 PloS one Discussion HIV T369A;T369V 60;142 65;147 RT 43 45 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Mutation N348I was verified by Yap et al at the end of 2007 to result in low resistance to AZT, with its degree of AZT resistance increasing with the number of TAMs. 2012 PloS one Discussion HIV N348I 9 14 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Mutations T369V/I and A371V emerged in the drug-naive patients, but the frequencies were relatively low and there was a significant difference between the subtype B and the subtype C. 2012 PloS one Discussion HIV A371V;T369I;T369V 22;10;10 27;17;17 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Nikolenko et al reported in 2007 that such mutations as E312Q, G335C/D, N348I, A360I/V, V365I and A376S at the connection domain could confer resistance to AZT to a certain extent. 2012 PloS one Discussion HIV A360I;A360V;A376S;E312Q;G335C;G335D;N348I;V365I 79;79;98;56;63;63;72;88 86;86;103;61;70;70;77;93 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Our findings showed that the resistance level was enhanced by 2.08~7.14 FCs to NNRTIs when the mutations T369V or A371V occurred alone. 2012 PloS one Discussion HIV A371V;T369V 114;105 119;110 NNRTI 79 85 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Phenotypic tests verified that the mutations A371V and T369V could enhance resistance to AZT and EFV, whereas the other 5 mutations could enhance the replication fitness of viruses relative to pNL4-3wild. 2012 PloS one Discussion HIV A371V;T369V 45;55 50;60 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The discrepancy of IC50 for AZT between viruses pNL4-3T369A and pNL4-3T369V was 101-fold, and variation T369A promoted the replication fitness of virus but T369V enhanced the resistance level of virus to antiviral drugs. 2012 PloS one Discussion HIV T369A;T369V;T369A;T369V 54;70;104;156 59;75;109;161 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The impact of T369V on NVP was significant, for the fold change was 5.08 fold relative to wild type virus pNL4-3wild. 2012 PloS one Discussion HIV T369V 14 19 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The mutation A371V is considered a polymorphism of CRF01_AE in the C-terminal half of RT, which did not confer resistance by itself but conferred significant resistance to NRTIs with TAMs, especially combined with TAM-II. 2012 PloS one Discussion HIV A371V 13 18 NRTI;RT 172;86 177;88 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The review mentioned that the compensatory mutation D488E occurs more frequently in subtype C than in subtype B, while the inverse is true for mutation Q547Q. 2012 PloS one Discussion HIV D488E;Q547Q 52;152 57;157 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. The susceptibility test for NVP showed that the resistant level of virus pNL4-3T369V was enhanced whereas the replication fitness of the other 6 mutant viruses was superior to the virus pNL4-3wild. 2012 PloS one Discussion HIV T369V 79 84 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. Two mutations (D123E and V292I) identified in this study are located at the DNA polymerase domain and the other 5 (K366R, T369A, T369V, A371V and I375V) at the connection domain. 2012 PloS one Discussion HIV A371V;D123E;I375V;K366R;T369A;T369V;V292I 136;15;146;115;122;129;25 141;21;151;120;127;134;30 Pol 80 90 23144802 Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China. We inferred from previous findings that the impact of mutations T369V and A371V on RT inhibitors is not significant if occurring alone, but the resistance level would be enhanced if the mutations occur in combination with TAMs. 2012 PloS one Discussion HIV A371V;T369V 74;64 79;69 RT 83 85 23152614 Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. A mutation in the core domain (K41A) abrogated the ability of Tat to down-regulate beta-catenin signaling. 2012 The Journal of neuroscience Discussion HIV K41A 31 35 Tat 62 65 23152614 Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. Further, mutation of Cys30 to glycine abrogated the ability of Tat to diminish TOPflash activity. 2012 The Journal of neuroscience Discussion HIV C30G 21 37 Tat 63 66 23199801 Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. In addition, the burden of DRMs found in our survey was consistent with previous studies in which prevalence of DRMs showed highly contrasted results, with NNRTI mutations ranging from 47 to 100%, the M184V/I mutation from 24 to 81%, and any TAM from 0 to 63%. 2012 Journal of the International AIDS Society Discussion HIV M184I;M184V 201;201 208;208 NNRTI 156 161 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. In this view maturation destabilizes the virus core, facilitating its dissociation in the newly infected cell and perhaps facilitating reverse transcription of the genome." The transdominant effects of cell activation, HSP90AB1 expression, and increased temperature independently rescued the CA-mutant viruses, and further analysis of the N139A mutant will determine if structural motifs in or around this residue regulate HIV core uncoating in an infected cell. 2013 Virology Discussion HIV N139A 339 344 RT;Capsid 135;292 156;294 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Of the six CA mutants studied, the N139A mutant virus appeared to most benefit from expression of HSP90AB1in the target cell as well as from increased temperature. 2013 Virology Discussion HIV N139A 35 40 Capsid 11 13 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. The N139A mutation does not affect core stability or morphology but, because maturation of the HIV core occurs in preparation for uncoating, mutations at this position might prevent access to essential CA-interacting host factors in the infected cell. 2013 Virology Discussion HIV N139A 4 9 Capsid 202 204 23200770 Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. These observations are in agreement with the second-site suppressor CA mutation for which the T261I and R132T compensatory mutations restored infectivity to CA-mutants with both unstable cores and hyperstable cores. 2013 Virology Discussion HIV R132T;T261I 104;94 109;99 Capsid;Capsid 68;157 70;159 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? However, some authors have warned about the fact that d4T-based initial therapy in patients infected with subtype C virus selects for a broader array of mutations, including the K65R mutation, conferring resistance to d4T, ddI, ABC, 3TC, FTC, and TDF. 2012 PloS one Discussion HIV K65R 178 182 23236346 Monitoring HIV viral load in resource limited settings: still a matter of debate? The majority of samples amplified from failing patients carried out M184V RAM (high level resistance to 3TC/FTC), NNRTI resistance associated mutations (cross resistance to NVP and EFV), as well as several thymidine analogue resistance mutations (TAMS), conferring different degrees of resistance to NRTIs. 2012 PloS one Discussion HIV M184V 68 73 NNRTI;NRTI 114;300 119;305 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. As reported previously, E407K near the V3 loop in SU was primarily responsible for the loss of interaction with CD134. 2012 Retrovirology Discussion HIV E407K 24 29 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. Interestingly, both 34TF10 and PPRcr share the E407K mutation that eliminated CD134 binding by PPRcr, yet 34TF10 has maintained CD134 binding capacity even though it is not required for infection. 2012 Retrovirology Discussion HIV E407K 47 52 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. Results in the present study show that E407K alone or in combination with other mutations in Env including mutations in TM (E656K and V817I) contributed to enhance entry via CXCR4 without requirement for primary interaction with CD134 (Table 1). 2012 Retrovirology Discussion HIV E407K;E656K;V817I 39;124;134 44;130;139 Env 93 96 23255871 Mapping of Receptor Binding Interactions with the FIV surface Glycoprotein (SU); Implications Regarding Immune surveillance and cellular Targets of Infection. The two tissue culture adapted (TCA) isolates share 4 mutations that distinguish both isolates from FIV-PPR, including V817I in TM. 2012 Retrovirology Discussion HIV V817I 119 124 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Integrase drug resistance profiles in four treatment failing patients with drug resistance followed two typical pathways, Q148H/G140S (one case) and N155H/V151I (three patients), associated with high level resistance to raltegravir and cross-resistance to elvitegravir . 2012 BMC infectious diseases Discussion HIV G140S;N155H;Q148H;V151I 128;149;122;155 133;154;127;160 IN 0 9 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. NRTI drug resistance mutations (thymidyne analog mutations and M184V) were present in six (50%) of the twelve treatment failing patients prior to RAL introduction. 2012 BMC infectious diseases Discussion HIV M184V 63 68 NRTI 0 4 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Of note, in our study the E157Q mutation was observed mostly among phylogenetically related subtype B infected intravenous drug users (Figure 1A), and was not associated with higher ratio of the virological failure. 2012 BMC infectious diseases Discussion HIV E157Q 26 31 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Of note, in the patient with the Q148H/G140S salvage treatment option with dolutegravir was also lost due to the resistance associated with this pathway . 2012 BMC infectious diseases Discussion HIV G140S;Q148H 39;33 44;38 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Of the noted variants, four (L68V, T97A, V151I, E157Q) have previously been described as polymorphic, occurring in >1% of integrase sequences . 2012 BMC infectious diseases Discussion HIV E157Q;L68V;T97A;V151I 48;29;35;41 53;33;39;46 IN 122 131 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Stepwise accumulation of mutations was observed in two patients with N155H followed by the secondary E92Q, V151I and/or G163R mutations resulting in further increase raltegravir and elvitegravir resistance and often enhanced replicative capacity . 2012 BMC infectious diseases Discussion HIV E92Q;G163R;N155H;V151I 101;120;69;107 105;125;74;112 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. The N155H pathway is also associated with smaller reduction in the RAL susceptibility than the Q148H, moreover, double Q148H/G140S mutants were found to be fitter than the E92Q/N155H ones . 2012 BMC infectious diseases Discussion HIV E92Q;G140S;N155H;N155H;Q148H;Q148H 172;125;4;177;95;119 176;130;9;182;100;124 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. These integrase mutations were more prevalent in the subtype B viruses with E157Q occurring at higher frequencies than previously reported . 2012 BMC infectious diseases Discussion HIV E157Q 76 81 IN 6 15 23259737 HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland. Time to InI resistance development in the observed patients did not exceed few months, except for one case with the double Q148H/G140S mutant, which is in accordance to the data on the low genetic barrier for the integrase inhibitors and rapid selection of the resistant variants . 2012 BMC infectious diseases Discussion HIV G140S;Q148H 129;123 134;128 IN;IN 213;8 222;11 23270497 Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China. These DR mutations (M184I, K103N/S, Y181C and K101E) could derive from ART-treated patients in Yunnan. 2012 BMC infectious diseases Discussion HIV K101E;K103N;K103S;M184I;Y181C 46;27;27;20;36 51;34;34;25;41 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Finally, N348I is known to cause resistance to both NRTIs and NNRTIs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV N348I 9 14 NNRTI;NRTI 62;52 68;57 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Hence, this new class of RT inhibitors should be able to efficiently block viruses that carry clinically relevant mutations, including the new connection domain mutation N348I. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV N348I 170 175 RT 25 27 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. showed that N348I enhances resistance to AZT through both RNase H-dependent and -independent mechanisms. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV N348I 12 17 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The A62V/V75I/F77L/F116Y/Q151M set of mutations is known as the "Q151M" complex RT, and has been known as a multidrug-resistance mutation, since the latter mutations are known to be involved in resistant variants with reduced susceptibility to dideoxynucleotides and to AZT. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV A62V;F116Y;F77L;Q151M;V75I;Q151M 4;19;14;25;9;65 8;24;18;30;13;70 RT 80 82 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. The D67N/K70R/L210Q/T215F set of mutations are the classical thymidine-associated mutations (TAMs), which are known to cause resistance to AZT by enhancing excision of AZT-terminated primers. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV D67N;K70R;L210Q;T215F 4;9;14;20 8;13;19;25 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. This resistance was shown to be caused by N348I, a mutation at the connection subdomain of HIV-1 RT. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV N348I 42 47 RT 97 99 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. Unlike D67N/K70R/L210Q/T215F RT, the Q151M complex decreases susceptibility to NRTIs by decreasing incorporation efficiency of the inhibitors rather than increasing excision and unblocking of chain-terminated primers. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV D67N;K70R;L210Q;T215F;Q151M 7;12;17;23;37 11;16;22;28;42 NRTI;RT 79;29 84;31 23273211 Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant. We report that both EFdA-TP and ENdA-TP are very potent inhibitors of N348I, D67N/K70R/L210Q/T215F, D67N/K70R/L210Q/T215F/N348I, and A62V/V75I/F77L/F116Y/Q151M RTs. 2012 Cellular and molecular biology (Noisy-le-Grand, France) Discussion HIV A62V;D67N;D67N;F116Y;F77L;K70R;K70R;L210Q;L210Q;N348I;Q151M;T215F;T215F;V75I;N348I 133;77;100;148;143;82;105;87;110;122;154;93;116;138;70 137;81;104;153;147;86;109;92;115;127;159;98;121;142;75 RT 160 163 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. Notably, a positive RNA OLA at positions M184V, N88D or L80M was highly sensitive for virologic failure (sensitivity: 0.93, 1.0 and 1.0, respectively). 2013 BMC infectious diseases Discussion HIV L80M;M184V;N88D 56;41;48 60;46;52 23280237 Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. The detection of the resistance mutations M184V, N88D and L90M by DNA-OLA was highly sensitive for virologic failure in this cohort treated with lamivudine-azidothymidine-nelfinavir as first-line therapy. 2013 BMC infectious diseases Discussion HIV L90M;M184V;N88D 58;42;49 62;47;53 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Considering the positive association of mutation D30N and N88D, it would be interesting to study how N88D influences the structure of D30N in complex with this new inhibitor 1. 2013 Journal of medicinal chemistry Discussion HIV D30N;D30N;N88D;N88D 49;134;58;101 53;138;62;105 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. D30N mutation is the major mutation associated with resistance to NFV, which has been suggested to arise from the change of conformational entropy upon inhibitor binding. 2013 Journal of medicinal chemistry Discussion HIV D30N 0 4 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutation R8Q exhibits higher sensitivity to compound 1 than other mutations studied here, suggesting that compound 1 may be a good inhibitor against viral strains bearing R8Q mutation. 2013 Journal of medicinal chemistry Discussion HIV R8Q;R8Q 9;171 12;174 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Mutation R8Q, however, has rarely been found in resistant clinical isolates. 2013 Journal of medicinal chemistry Discussion HIV R8Q 9 12 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Our previous studies suggested that the loss of dimer stability due to I50V mutation was a major contributor to the diminished catalytic activity and inhibition of PRI50V. 2013 Journal of medicinal chemistry Discussion HIV I50V 71 75 PR 164 166 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Our structural analysis also showed that mutation D30N introduced changes in its interactions with neighboring residues Thr74 and Asn88. 2013 Journal of medicinal chemistry Discussion HIV D30N 50 54 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Similarly, our study suggests that viral strains containing D30N or I50V are likely to show resistance to inhibitor 1 given their Ki values of 8.9 and 30.9 nM for PRD30N and PRI50V, respectively. 2013 Journal of medicinal chemistry Discussion HIV D30N;I50V 60;68 64;72 PR;PR 163;174 165;176 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Substitution of the smaller side chains in PRI50V and PRV82A resulted in the loss of their interactions with inhibitor; however, mutation V82A caused a shift of its main chain atoms to compensate for the loss. 2013 Journal of medicinal chemistry Discussion HIV V82A 138 142 PR;PR 43;54 45;56 23298236 Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease. Therefore, mutations D30N, I50V, I54M, and V82A exhibit similar effects on both inhibitors, although inhibitor 1 is less effective than DRV on PRI50V. 2013 Journal of medicinal chemistry Discussion HIV D30N;I50V;I54M;V82A 21;27;33;43 25;31;37;47 PR 143 145 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Despite the reported paucity of K65R at the current time, a prevalence of 1% or greater in the HIV-positive population would still signify a large number of potentially transmissible viruses, especially in the setting of selective pressure from tenofovir. 2012 Journal of the International AIDS Society Discussion HIV K65R 32 36 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Finally, the prevalence of reported K65R reviewed here may be underestimated due to the 15 to 20% detection threshold of population-based sequencing and the potential for DNA archiving. 2012 Journal of the International AIDS Society Discussion HIV K65R 36 40 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. In this analysis of globally available HIV-1 pol sequences, the prevalence of RT mutations associated with tenofovir resistance, including K65R, across diverse subtypes and recombinant forms is low (0.10%, 20/19,823). 2012 Journal of the International AIDS Society Discussion HIV K65R 139 143 Pol;RT 45;78 48;80 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. In two large surveillance studies from the United States, out of 2030 newly HIV-positive individuals and 1585 treatment-naive individuals, there were only one (0.9%) and three (0.19%) occurrences of K65R, respectively. 2012 Journal of the International AIDS Society Discussion HIV K65R 199 203 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. K65R, in addition to conferring resistance to tenofovir, also leads to significant reductions in viral replication and fitness. 2012 Journal of the International AIDS Society Discussion HIV K65R 0 4 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Other tenofovir-associated mutations, such as K70E and T69 insertions, were either rare or absent. 2012 Journal of the International AIDS Society Discussion HIV K70E 46 50 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Our results support the low prevalence of K65R and extend the finding to other, globally predominant, non-B subtypes. 2012 Journal of the International AIDS Society Discussion HIV K65R 42 46 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Subtype C, the predominant worldwide subtype, did not have an increased rate of K65R in this dataset, despite previously reported higher rates of occurrences of this mutation in this subtype. 2012 Journal of the International AIDS Society Discussion HIV K65R 80 84 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. The limited numbers of available naive sequences of each of the non-B subtypes, including subtype C, and the rare occurrence of K65R overall, mandate further monitoring to examine K65R global occurrence and transmission. 2012 Journal of the International AIDS Society Discussion HIV K65R;K65R 128;180 132;184 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. The most common non-K65R tenofovir-associated resistance mutations were TAMs, which are common in patients failing NRTI-based regimens. 2012 Journal of the International AIDS Society Discussion HIV K65R 20 24 NRTI 115 119 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. The observed non-significant trend in K65R prevalence in subtype B compared to non-subtype B sequences likely reflects higher reporting from, and the widespread use of, tenofovir-containing regimens in resource-rich settings, where subtype B is predominant. 2012 Journal of the International AIDS Society Discussion HIV K65R 38 42 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. The previously reported transmission of K65R in subtype B infected patients is less than 1%, reflecting resource-rich settings where tenofovir and other NRTIs are widespread. 2012 Journal of the International AIDS Society Discussion HIV K65R 40 44 NRTI 153 158 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. There was no detectable difference in the occurrence of K65R before or after 2004, despite the increased use of tenofovir as part of first-line or advanced anti-retroviral regimens since 2004. 2012 Journal of the International AIDS Society Discussion HIV K65R 56 60 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Though these mutations may be transmitted more commonly as individual mutations, sequences with three or more TAMs (inclusive of either M41L or L210W) can confer significantly reduced tenofovir activity and were observed in our dataset. 2012 Journal of the International AIDS Society Discussion HIV L210W;M41L 144;136 149;140 23305651 Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. Though uncommon and despite in vitro antagonism, K65R occurred with other mutations that impact viral fitness, including M184V in 35% (7/20) and L74V in 5% (1/20) of K65R-containing sequences. 2012 Journal of the International AIDS Society Discussion HIV K65R;K65R;L74V;M184V 49;166;145;121 53;170;149;126 23308067 Human tetherin exerts strong selection pressure on the HIV-1 group N Vpu protein. It also came as a surprise that just four amino acid changes in the TMD of the EK505 Vpu (E15A; V19A; IV25/26LL) rendered it active against human tetherin without disrupting the CD4, CD1d and NTB-A down-modulation functions (Figure 4). 2012 PLoS pathogens Discussion HIV E15A;V19A 90;96 94;100 Vpu 85 88 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. demographic and clinical data were similar between patients harboring L76V-mutated viruses and those with wild-type residue at position 76, no viral subtype analysis was performed. 2013 PloS one Discussion HIV L76V 70 74 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Differences have been previously observed in the genetic barrier to resistance in mutations associated with resistance to non nucleoside reverse transcriptase inhibitors (NNRTI) for the A98S and V106M mutations between HIV-1 B and C subtypes, or in mutations associated with resistance to integrase inhibitors between B and CRF02_AG subtypes. 2013 PloS one Discussion HIV A98S;V106M 186;195 190;200 NRTI;IN;NNRTI 126;289;171 158;298;176 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. For the first time a higher prevalence of the L76V mutation in "non-B"- than in B-infected patients was observed since 2008. 2013 PloS one Discussion HIV L76V 46 50 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In addition, further studies based on immuno-virological outcome of HIV-1 "non-B"-infected patients receiving PI-based regimen, especially in resource-limited settings, might help to assess the clinical implications of the presence of the L76V mutation. 2013 PloS one Discussion HIV L76V 239 243 PI 110 112 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In addition, the L76V mutation appeared more rapidly and was associated with less PI-RAM in "non-B" subtypes than in B subtype. 2013 PloS one Discussion HIV L76V 17 21 PI 82 84 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In conclusion, in this study assessing the prevalence of L76V PI RAM in "non-B"- and B-infected patients, we showed that the viral subtype could have an impact on the selection of this mutation. 2013 PloS one Discussion HIV L76V 57 61 PI 62 64 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In our study a shorter time since HIV diagnosis, a shorter time under antiretroviral-based therapy, and a lower number of PI in the therapeutic history were all significantly observed in "non-B"-infected patients when compared to B-infected patients exhibiting L76V-mutated viruses. 2013 PloS one Discussion HIV L76V 261 265 PI 122 124 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In our study, one hypothesis might be that the presence of pre-therapeutic gag polymorphisms could favor the selection of the L76V mutation. 2013 PloS one Discussion HIV L76V 126 130 Gag 75 78 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In our study, the covariation analysis did not allow to evidence different clustering of the L76V PI RAM with protease polymorphisms or other PI RAM according to the viral subtype. 2013 PloS one Discussion HIV L76V 93 97 PR;PI;PI 110;98;142 118;100;144 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In our study, the overall prevalence of L76V tends to decrease during the study period, with no statistical significance. 2013 PloS one Discussion HIV L76V 40 44 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In the database assessed by Young et al., the prevalence of L76V as single PI RAM was rare, found in 0.04% of the samples. 2013 PloS one Discussion HIV L76V 60 64 PI 75 77 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In the present study based on 179 patients, including 61 "non-B"-infected patients, exhibiting plasma virus with the L76V major drug resistance mutation in the protease region we showed that the selection of this mutation appeared earlier in infection history, earlier in therapeutic history and occurred in virus harboring a lower number of major PI resistance mutations in "non-B"-infected patients compared to subtype B-infected patients. 2013 PloS one Discussion HIV L76V 117 121 PR;PI 160;348 168;350 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. In the present study we described that the prevalence of L76V since 2008 is significantly higher in "non-B"-infected patients than in subtype B-infected patients. 2013 PloS one Discussion HIV L76V 57 61 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Interestingly, a higher prevalence of virus exhibiting the L76V mutation as single major PI RAM was observed in "non-B" sequences than in B sequences (10% vs 2%, respectively). 2013 PloS one Discussion HIV L76V 59 63 PI 89 91 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Overall in our database containing more than 29,000 sequences, we described a prevalence of the L76V mutation of 1.50% in all sequences and of 3.94% in viruses issued from PI-experienced patients. 2013 PloS one Discussion HIV L76V 96 100 PI 172 174 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. Several hypotheses may explain this apparent easier selection of the L76V mutation in the context of "non-B" subtypes. 2013 PloS one Discussion HIV L76V 69 73 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The covariation analysis we performed in our study showed that the L76V mutation clustered with the major PI RAM M46I as described in previous studies both in B and non-B viruses. 2013 PloS one Discussion HIV L76V;M46I 67;113 71;117 PI 106 108 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The most prevalent PI RAM detected with L76V was the M46I mutation, whatever the viral subtype, may be due to the use of indinavir. 2013 PloS one Discussion HIV L76V;M46I 40;53 44;57 PI 19 21 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. The overtime decrease of prevalence has been recently also described for the M184I/V and K103 resistance mutations. 2013 PloS one Discussion HIV M184I;M184V 77;77 84;84 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. These findings suggest that the more rapid selection of the L76V observed in "non-B" subtypes might not be explained by an association of the L76V with a specific protease polymorphism or PI RAM in "non-B" subtype. 2013 PloS one Discussion HIV L76V;L76V 60;142 64;146 PR;PI 163;188 171;190 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. These findings suggest that there is no lower genetic barrier to acquire the L76V in CRF02_AG than in subtype B, with a change from T to G in both cases. 2013 PloS one Discussion HIV L76V 77 81 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. This prevalence is similar to that described in previous studies reporting 1.16% of L76V in the study of Nijhuis et al. 2013 PloS one Discussion HIV L76V 84 88 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. This specific genotypic background of "non-B" subtypes protease may have a possible role in a more rapid selection of the L76V mutation. 2013 PloS one Discussion HIV L76V 122 126 PR 55 63 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. To our knowledge, this is the first time that a differential prevalence of the L76V depending of the viral subtype was described. 2013 PloS one Discussion HIV L76V 79 83 23349869 Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes. We also showed that the L76V mutation was associated with a lower number of major PI RAMs in "non-B" than in subtype B sequences. 2013 PloS one Discussion HIV L76V 24 28 PI 82 84 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. In fact, G330E slightly decreased restriction stemming from Arg332 and/or Arg335 mutations and seemed to decrease binding of R332G-R335G to in vitro assembled HIV-1 CA-NC complexes. 2013 Virus research Discussion HIV G330E;R332G;R335G 9;125;131 14;130;136 NC;Capsid 168;165 170;167 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. Interestingly, the inhibitory effect of G330E is not additive to that of R332G or R335G, while R332G and R335G do have additive effects. 2013 Virus research Discussion HIV G330E;R332G;R332G;R335G;R335G 40;73;95;82;105 45;78;100;87;110 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. The change in charge associated with the substitution is crucial to G330E inhibitory activity, as was previously found to be the case for other mutants in this region. 2013 Virus research Discussion HIV G330E 68 73 23357295 A novel aminoacid determinant of HIV-1 restriction in the TRIM5alpha variable 1 region isolated in a random mutagenic screen. This mutation, G330E, was isolated using a degenerated oligonucleotide, a technique which to our knowledge had never been applied to generate anti-HIV-1 restriction factors. 2013 Virus research Discussion HIV G330E 15 20 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. 2, L33S did not significantly affect replication kinetics compared with HIV-1WT, suggesting that L33S might sustain binding affinity with C-HR to form a stable six-helix bundle. 2013 The international journal of biochemistry & cell biology Discussion HIV L33S;L33S 3;97 7;101 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. A possible hydrogen bond between K137 and D43 may partially restore the reported loss in six-helix bundle stability conferred by the N43D mutation, suggesting that E137K can compensate for losses in the interactions between N-HRN43D and C-HR. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K;N43D;N43D 164;133;228 169;137;232 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. A prevalent polymorphism, E137K, which was associated with N43D in vivo, has been proven to restore infectivity that has been impaired by N43D. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K;N43D;N43D 26;59;138 31;63;142 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Although our work clearly demonstrates that L33S is involved in resistance to T-20 derivatives, it was not possible to discern whether L33S affected binding affinity to C-HR in the CD analyses because L33 was not in the sequence of the N36 N-HR peptide that we had to use in this study. 2013 The international journal of biochemistry & cell biology Discussion HIV L33S;L33S 44;135 48;139 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Because E137K restored binding affinity with N-HR similar to the S138A mutation, we expected that introduction of E137K into T-20 would effectively suppresses replication of T-20-resistant HIV-1. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K;E137K;S138A 8;114;65 13;119;70 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. E137K did not affect susceptibility to all peptide fusion inhibitors by itself, but in combination with primary mutations, it remarkably enhanced resistance to T-20S138A. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K 0 5 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. For example, in the case of the most commonly used drugs that target HIV reverse transcriptase (RT), the virus can develop multidrug resistance by either the Q151M complex pathway or by accumulation of thymidine associated mutations (TAMs). 2013 The international journal of biochemistry & cell biology Discussion HIV Q151M 158 163 RT;RT 73;96 94;98 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Hence, nucleotide changes for L33S do not require compensatory mutations to maintain secondary structure of the RRE. 2013 The international journal of biochemistry & cell biology Discussion HIV L33S 30 34 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Here we demonstrate that the introduction of a secondary resistance mutation (E137K) in the backbone of a peptide fusion inhibitor is a useful change that results into more potent fusion inhibitors, even for HIV-1 strains that are resistant to peptide fusion inhibitors. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K 78 83 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. In the case of the T-20S138A inhibitor, the N43D/S138A may also act as such polymorphisms despite the presence of primary mutations and preferentially affect the emergence of specific mutations. 2013 The international journal of biochemistry & cell biology Discussion HIV N43D;S138A 44;49 48;54 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. In this study, L33S conferred little resistance to C34 in this study, while it was previously reported to confer up to 10-fold resistance, suggesting that some other viral background might affect the resistance, since Armand et al. 2013 The international journal of biochemistry & cell biology Discussion HIV L33S 15 19 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. In this study, L44M did not confer resistance to all peptide inhibitors; however, L44M in combination with other mutations (I37N/N126K) remarkably enhanced resistance to T-20S138A, suggesting that L44M serves as a secondary mutation to enhance resistance to T-20S138A. 2013 The international journal of biochemistry & cell biology Discussion HIV I37N;L44M;L44M;L44M;N126K 124;15;82;197;129 128;19;86;201;134 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. L33S was previously reported in HIV-1 variants resistant to T-20, C34, and a membrane-anchored C-HR-derived peptide, M87. 2013 The international journal of biochemistry & cell biology Discussion HIV L33S 0 4 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Moreover, introduction of the E137K change into N43D/S138A enhanced the viral replication kinetics as shown in. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K;N43D;S138A 30;48;53 35;52;58 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. N126K also enhances resistance to some fusion inhibitors by helping recover losses in intra-gp41 interactions that were caused by primary mutations, such as N43D. 2013 The international journal of biochemistry & cell biology Discussion HIV N43D;N126K 157;0 161;5 gp41 92 96 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Other substitutions at position 37 (I37T or I37K) also conferred resistance to T-20 and C34, suggesting that I37 in N-HR is critical for the attachment of C-HR-derived peptide fusion inhibitors. 2013 The international journal of biochemistry & cell biology Discussion HIV I37K;I37T 44;36 48;41 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Selection of T-20S138A-resistance starting with wild-type HIV-1 resulted in the emergence of I37N and L44M substitutions, which were located in the N-HR region that is thought to interact with T-20. 2013 The international journal of biochemistry & cell biology Discussion HIV I37N;L44M 93;102 97;106 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Since E137K is located within the T-20 sequence, we synthesized and characterized the activity of novel T-20-based peptides containing E137K (T-20E137K). 2013 The international journal of biochemistry & cell biology Discussion HIV E137K;E137K;E137K 146;6;135 151;11;140 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. The L33S mutation is located in the loop of stem IIc of the RRE. 2013 The international journal of biochemistry & cell biology Discussion HIV L33S 4 8 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. The L44M mutation has only been observed in subtype B HIV-1-infected patients treated with T-20, and conferred weak resistance to T-20. 2013 The international journal of biochemistry & cell biology Discussion HIV L44M 4 8 HIV infections 54 68 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Therefore, it is likely that L33S has little effect on replication kinetics. 2013 The international journal of biochemistry & cell biology Discussion HIV L33S 29 33 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. Through the CD anlysis, the N126K and E137K mutations in the C-HR may act as compensatory mutations for impaired interaction by a primary mutation, I37N and N43D in the N-HR, respectively. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K;I37N;N126K;N43D 38;148;28;157 43;152;33;161 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We examined the antiviral activity of E137K- and E137K/S138A-containing T-20 and C34 to T-20S138A-resistant HIV-1. 2013 The international journal of biochemistry & cell biology Discussion HIV S138A;E137K;E137K;S138A 92;38;49;55 97;43;54;60 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. We found that T-20E137K had similar antiviral activity with other T-20 derivatives such as T-20S138A and T-20E137K/S138A. 2013 The international journal of biochemistry & cell biology Discussion HIV E137K;E137K;S138A;S138A 18;109;95;115 23;114;100;120 23357451 Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design. When we selected T-20S138A-resistant HIV-1 (HIV-1N43D/S138A) we obtained a somehow different set of mutations that included L33S, which is located at the presumed T-20 binding site at N-HR, as well as I37N, N43D, and L44M. 2013 The international journal of biochemistry & cell biology Discussion HIV I37N;L33S;L44M;N43D;S138A 201;124;217;207;54 205;128;221;211;59 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Analysis of recombinant V3 mutant viruses showed that while the S11R mutation conferred efficient CXCR4 usage, the D25K V3 mutant entered CXCR4-expressing cells less efficiently than cells expressing CCR5, in agreement with findings in infected individuals that changes in V3 position 25 alone are not highly predictive of coreceptor switching. 2013 Retrovirology Discussion HIV D25K;S11R 115;64 119;68 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. But importantly, deep sequencing failed to reveal the presence of D25K mutation associated with tropism switch in FF94 in the clone 8 virus inoculum, consistent with findings that multiple long-term cultures of clonal virus variants on PBMCs results in only very few mutations in the V3-V4 regions. 2013 Retrovirology Discussion HIV D25K 66 70 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Fifteen of over 21,000 sequences analyzed (0.07%) harbored the S11R mutation, raising the possibility that the R5X4 variant could have been co-transmitted and eventually outgrew in macaque EN31 which failed to mount a neutralizing antibody response. 2013 Retrovirology Discussion HIV S11R 63 67 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. In contrast, while the S11R variant was also present in the SHIVSF162P3N clone 8 virus stock (0.11%), it was not detected by clonal sequence analysis in the conventional macaque FF94 at terminal disease stage. 2013 Retrovirology Discussion HIV S11R 23 27 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. It is conceivable that the S11R variant was not co-transmitted in this animal. 2013 Retrovirology Discussion HIV S11R 27 31 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Moreover, the D25K V3 mutational event in FF94 occurred first in the lymph node where naive T cells that express high levels of CXCR4 are enriched, in agreement with data published by us and others that peripheral LNs are the prefer sites of X4 evolution and amplification. 2013 Retrovirology Discussion HIV D25K 14 18 23369442 Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques. Notably, emergence of the dual-tropic D25K variant in the LN was in the presence of neutralizing antibody (ID50 titers of ~150 against the inoculating clone 8 virus at 46 wpi; Figure 5), with clonal analysis of the viral quasispecies showing increasing dominance of the D25K V3 variant in LN and blood cells, but not in the plasma (Figure 4C). 2013 Retrovirology Discussion HIV D25K;D25K 38;270 42;274 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. All patients had genotypic resistance or possible resistance to AZT, D4T and ABC because the pressure of three or more AZT-specific mutations including T214Y is thought to confer resistance to D4T and ABC. 2012 Annals of Saudi medicine Discussion HIV T214Y 152 157 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. M361, M184V and K103N mutations were frequent for the PI, NRTI, and NNRT classes, respectively. 2012 Annals of Saudi medicine Discussion HIV K103N;M184V 16;6 21;11 NRTI;PI 58;54 62;56 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. RT enzyme possessing the M184V mutation exhibit reduced processability and increased fidelity compared with wild-type enzymes. 2012 Annals of Saudi medicine Discussion HIV M184V 25 30 RT 0 2 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. The K103N is the most common RT gene mutation observed following an NNRT-containing regimen. 2012 Annals of Saudi medicine Discussion HIV K103N 4 9 RT 29 31 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. The K103N mutation was detected in patients receiving efivarenz and who had a plasma viral load rebound. 2012 Annals of Saudi medicine Discussion HIV K103N 4 9 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. The M184V mutation in the RT gene is associated with resistance to 3TC and inverse susceptibility to others, as has been shown in clinical and in vitro studies. 2012 Annals of Saudi medicine Discussion HIV M184V 4 9 RT 26 28 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. The most common mutations were piM36I and piL90M, found in 70% and 42% of our patients, respectively. 2012 Annals of Saudi medicine Discussion HIV L90M;M36I 42;31 48;37 PI;PI 31;42 33;44 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. This high proportion of patients harboring the M184V mutation could be because 80% of our viremic patients were receiving 3TC at the time of testing. 2012 Annals of Saudi medicine Discussion HIV M184V 47 52 23396017 Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy. We detected the rtK103N mutation in three viremic children who were receiving efavirenz (NRTI). 2012 Annals of Saudi medicine Discussion HIV K103N 18 23 NRTI;RT 89;16 93;18 23401688 Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil. Moreover, no decrease in viral fitness is expected for mutations to this class, and they tend to persist longer and be more readily detectable than others that interfere with viral fitness, such as M184V. 2013 Advances in virology Discussion HIV M184V 198 203 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Additionally, during selection studies in primary human cord blood mononuclear cells, it appeared as though a secondary mutation H51Y was often present . 2013 Retrovirology Discussion HIV H51Y 129 133 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Here, we have shown that the combination of mutations at positions H51Y and R263K define a unique resistance pathway for DTG. 2013 Retrovirology Discussion HIV H51Y;R263K 67;76 71;81 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. However, if the results reported here are further clinically validated, consideration should be given to exploring the possibility that the H51Y/R263K combination of mutations, perhaps in concert with other strategies, might reduce or prevent new cycles of HIV DNA integration into host cells. 2013 Retrovirology Discussion HIV H51Y;R263K 140;145 144;150 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In addition, we have continued our DTG tissue culture selection efforts for over one year and have not yet identified any potential compensatory mutations that might restore integrase function while increasing levels of drug resistance above those seen with the combination of R263K and H51Y. 2013 Retrovirology Discussion HIV H51Y;R263K 287;277 291;282 IN 174 183 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In contrast, we demonstrate that the combination of R263K together with H51Y simultaneously increased levels of resistance against DTG while diminishing both viral replicative capacity and integrase strand transfer activity. 2013 Retrovirology Discussion HIV H51Y;R263K 72;52 76;57 IN 189 198 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. In vitro selection experiments with both DTG and another second-generation compound termed MK-2048 have identified several mutations within the integrase coding region, including G118R, S153Y, and R263K that confer low-level resistance to these drugs . 2013 Retrovirology Discussion HIV G118R;R263K;S153Y 179;197;186 184;202;191 IN 144 153 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Perhaps, more importantly, this combination of mutations further diminished the ability of viral DNA to integrate within the host cell genome beyond the deficit associated with the R263K mutation alone. 2013 Retrovirology Discussion HIV R263K 181 186 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. The H51Y substitution on its own did not affect either DTG drug resistance, viral replication capacity, or integrase strand transfer enzymatic activity, as tested both biochemically and in cell-based assays. 2013 Retrovirology Discussion HIV H51Y 4 8 IN 107 116 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. This may be related to either the low replication capacity of viruses containing the H51Y/R263K combination or the poor integrase strand transfer capacity of enzymes containing these substitutions, or both. 2013 Retrovirology Discussion HIV H51Y;R263K 85;90 89;95 IN 120 129 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. We are currently in the process of studying whether the R263K and H51Y mutations in simian immunodeficiency virus (SIV) have similar effects as those described here. 2013 Retrovirology Discussion HIV H51Y;R263K 66;56 70;61 23432922 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. We believe that the fitness cost of the H51Y/R263K combination may explain the absence of resistance mutations in integrase inhibitor-naive patients treated to date with DTG , since viruses that possess these two mutations in tandem may replicate so poorly as to be undetectable by the conventional assays that were employed for detection of drug resistance in the above-referenced clinical studies. 2013 Retrovirology Discussion HIV H51Y;R263K 40;45 44;50 IN 114 123 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. Also, one study has reported the co-presence of M184I and E138K in 24% of hypermutated sequences of treated patients. 2013 Journal of the International AIDS Society Discussion HIV E138K;M184I 58;48 63;53 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. As the hypermutated sequences with DRM (M184I; M230I) had stop codons in the ORFs and the absence of these DRMs in the plasma viral RNA, it is unlikely that such proviral variants will mature and expand in vivo. 2013 Journal of the International AIDS Society Discussion HIV M184I;M230I 40;47 45;52 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. However, random polymorphisms of E138K/A were observed in the proviral DNA of both therapy-naive and experienced patients. 2013 Journal of the International AIDS Society Discussion HIV E138A;E138K 33;33 40;40 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. In contrast, co-evolution of M184I and E138K was not found in our hypermutated sequences. 2013 Journal of the International AIDS Society Discussion HIV E138K;M184I 39;29 44;34 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. The presence of drug resistance mutations like M184V, T215Y, K103N, and Y181C in plasma virus but not in the provirus in our study indicates that routine HIV RNA monitoring every six months and subsequent plasma viral genotyping at failure identifies the most recent viral populations circulating, although different sources of the two viral populations cannot be excluded. 2013 Journal of the International AIDS Society Discussion HIV K103N;M184V;T215Y;Y181C 61;47;54;72 66;52;59;77 23443042 Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. Thus, due to a suboptimal anti-APOBEC3G activity of HIV-1 Vif mutants, the HIV drug resistance mutations M184I and E138K may be induced in vitro without any drug exposure. 2013 Journal of the International AIDS Society Discussion HIV E138K;M184I 115;105 120;110 Vif 58 61 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. E89G RT and RNase H-deficient mutants share an increased fidelity of mispair extension in comparison with the wild-type RT. 2013 Nucleic acids research Discussion HIV E89G 0 4 RT;RT 5;120 7;122 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. For example, substituting Ala for Gly262 or Trp266 renders RTs with lower processivity, higher koff and increased tendency to introduce frameshift errors. 2013 Nucleic acids research Discussion HIV G262A 26 40 RT 59 62 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Frameshift errors made by the E89G mutant accumulated at well-known hotspots such as the one located at positions -34 to -36 of the lacZalpha gene. 2013 Nucleic acids research Discussion HIV E89G 30 34 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. However, in the case of mutant E478Q, differences with the wild-type HIV-1 (group M:subtype B RT) were not significant when assayed in the presence of 6 mM Mg2. 2013 Nucleic acids research Discussion HIV E478Q 31 36 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. However, unlike in the case of the mutants described in our study, E89G increased DNA polymerase processivity. 2013 Nucleic acids research Discussion HIV E89G 67 71 Pol 86 96 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In contrast, the BH10_WT RT showed a higher frameshift error rate than the RNase H-deficient mutant E478Q (Table 4). 2013 Nucleic acids research Discussion HIV E478Q 100 105 RT 25 27 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. In HIV-1 RT, mutations D443N and E478Q abolish RNase H activity while retaining wild-type DNA polymerase activity. 2013 Nucleic acids research Discussion HIV D443N;E478Q 23;33 28;38 Pol;RT 94;9 104;11 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Interestingly, the substitution of Gly for Glu89 did not have a major effect on the overall fidelity of the HIV-1HXB2 RT as determined in forward mutation assays, but as observed with the HIV-1 group O RNase H-deficient mutants, the E89G RT showed a relatively high tendency to introduce frameshift errors (both run and non-run-associated), and a higher accuracy for base substitutions in comparison with the wild-type RT. 2013 Nucleic acids research Discussion HIV E89G;E89G 233;35 237;48 RT;RT;RT 118;238;419 120;240;421 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. K65R, L74V, Q151N and M184I) have a relatively minor impact on error distribution, with frameshifts occurring mostly at nucleotide runs. 2013 Nucleic acids research Discussion HIV L74V;M184I;Q151N;K65R 6;22;12;0 10;27;17;4 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Previous reports have demonstrated that the RNase H-inactivating mutation D443N decreases HIV-1 group M subtype B RT processivity, and similar effects have been reported for its equivalent residue in MLV RT. 2013 Nucleic acids research Discussion HIV D443N 74 79 RT;RT 114;204 116;206 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Previously, we showed that the frameshift error rate of O_WT and O_V75I RTs was very low (<1.85 x 10-6), as determined with the M13mp2 lacZalpha-based assay. 2013 Nucleic acids research Discussion HIV V75I 67 71 RT 72 75 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The different effects of E478Q on the dissociation rate constants of HIV-1 group O and group M RTs could be related to structural differences between the corresponding RNase H domains. 2013 Nucleic acids research Discussion HIV E478Q 25 30 RT 95 98 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The higher frameshift error rates of mutants O_V75I/D443N and O_D443N RTs correlated well with their high koff values, in agreement with their expected contribution to slippage. 2013 Nucleic acids research Discussion HIV D443N;D443N;V75I 52;64;47 57;69;51 RT 70 73 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. The results of the forward mutation fidelity assays show that both HIV-1 group O and group M RTs bearing mutations D443N or E478Q are more accurate than the wild-type enzyme. 2013 Nucleic acids research Discussion HIV D443N;E478Q 115;124 120;129 RT 93 96 23444139 Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. We did not observe differences in the distribution of termination sites during processive DNA synthesis, except in the case of mutants O_D443N and O_E478Q at position +102, where both enzymes showed an increased tendency to introduce large deletions. 2013 Nucleic acids research Discussion HIV D443N;E478Q 137;149 142;154 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Accordingly, our NMR data showed that the molecular interactions between CA and CypA were altered by the V86M mutation, as was the isomerisation reaction catalysed by CypA. 2013 Retrovirology Discussion HIV V86M 105 109 Capsid 73 75 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Altogether, our results show that restriction of V86M CA HIV-1 is largely insensitive to the presence of functional CypA, while the same virus is still inhibited in human cells devoid of CypA. 2013 Retrovirology Discussion HIV V86M 49 53 Capsid 54 56 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Altogether, V86M can confer HIV-1 protection against restriction by various TRIM5alpha proteins in specific replication settings. 2013 Retrovirology Discussion HIV V86M 12 16 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. In order to investigate the mechanism of CA-V86M HIV-1 resistance to R332G-R335G TRIM5alphahu, we analyzed the role of CypA in the restriction. 2013 Retrovirology Discussion HIV R332G;R335G;V86M 69;75;44 74;80;48 Capsid 41 43 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Indeed, restriction of HIV-1 by CPSF6-358, a truncated form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6), is counteracted by the mutation N74D in CA. 2013 Retrovirology Discussion HIV N74D 178 182 Capsid 186 188 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. It should be informative to analyze whether V86M modifies the interactions between HIV-1 CA and these nucleoporins. 2013 Retrovirology Discussion HIV V86M 44 48 Capsid 89 91 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. On the basis of our data, we do not expect V86M to be highly significant in an in vivo context, although this is of course rather hazardous to predict. 2013 Retrovirology Discussion HIV V86M 43 47 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Our data show that V86M indeed confers some level of protection against various mutants of TRIM5alphahu, at least in the context of single-cycle infections with HIV-1 vectors. 2013 Retrovirology Discussion HIV V86M 19 23 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Our initial efforts had not led us to isolate R332G-R335G TRIM5alphahu-resistant HIV-1 by serial passaging. 2013 Retrovirology Discussion HIV R332G;R335G 46;52 51;57 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. Sodroski and collaborators have isolated the V86M mutant in HeLa-CD4 cells, which we have not tested here. 2013 Retrovirology Discussion HIV V86M 45 49 23448277 The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import. We then decided to test whether V86M, an HIV-1 CA mutant isolated from cells expressing TRIM5alpharh by the Sodroski group and shown to confer some level of protection against this orthologue, would also make HIV-1 resistant to TRIM5alphahu mutants. 2013 Retrovirology Discussion HIV V86M 32 36 Capsid 47 49 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. An example is the discrepancy between our failure to find the mutation G190AS among drug-naive individuals, in both subtypes, and the transmission of this mutation to subtype-B infected individuals reported elsewhere. 2013 PloS one Discussion HIV G190A;G190S 71;71 77;77 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. By contrast, individuals failing EFV treatment had NNRTI-related mutations independently of subtype, in particular K103N and G190AS. 2013 PloS one Discussion HIV G190A;G190S;K103N 125;125;115 131;131;120 NNRTI 51 56 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. In addition, mutation frequencies in A/AE-infected patients genotyped prior to 2001, who were initially given mono- or 2-drug therapy, were similar to those found in the general B-population, except that D30N was not found in any of the 9 A/AE patients failing NFV while it was found in 23% of B-patients failing this drug. 2013 PloS one Discussion HIV D30N 204 208 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. In particular, resistance-conferring mutations, including the protease mutation L90M and the RT mutations K103N and T215Y were chain-transmitted to drug-naive individuals. 2013 PloS one Discussion HIV K103N;L90M;T215Y 106;80;116 111;84;121 PR;RT 62;93 70;95 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. The influence of the A62V mutation and other secondary mutations on long-term cART outcomes is also still unresolved. 2013 PloS one Discussion HIV A62V 21 25 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. the protease mutations M36I, L89M or the RT mutation R211S, and others (Tables 5 and 6; see also Kantor et al.). 2013 PloS one Discussion HIV L89M;M36I;R211S 29;23;53 33;27;58 PR;RT 4;41 12;43 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. The trend is not surprising as diminution in TAMs under modern cART is attributed to the use of TDF and FTC instead of ZDV and 3TC, resulting in emergence of mainly K65R and M184V but not of TAMs. 2013 PloS one Discussion HIV K65R;M184V 165;174 169;179 23469241 Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy. While K103N found its way to this population (3%), G190AS, which developed in 21% of the treated individuals, was not found prior to treatment (Table 5). 2013 PloS one Discussion HIV G190A;G190S;K103N 51;51;6 57;57;11 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Although S375A affinity for sCD4 is almost unchanged compared to WT, KR21 inhibitory potency for this mutant is 20-fold reduced (Figure 13). 2013 Biochemistry Discussion HIV S375A 9 14 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. In addition to the single mutation studied here (S375A), testing additional predictions of the current model experimentally. 2013 Biochemistry Discussion HIV S375A 49 54 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. Interestingly, the S375W gp120 mutant was found to be resistant to the parent 12p1 peptide while we observed that S375A has reduced sensitivity to PTs (Figure 13). 2013 Biochemistry Discussion HIV S375A;S375W 115;19 120;24 gp120 25 30 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. introduction of phenylalanine in place of Ile4 on peptide to improve its affinity or mutating W112 or I109 on gp120 to probe the effect on peptide binding) can provide more direct cues to refining the model using more rigorous simulation methods. 2013 Biochemistry Discussion HIV I4F 16 46 gp120 110 115 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. The significantly larger side chain of S375W would completely obstruct the critical peptide tryptophan from accessing contacts inside the F43 pocket. 2013 Biochemistry Discussion HIV S375W 39 44 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. To quantify the extent of this effect, we tested the KR21 inhibitory potency against S375A interaction with sCD4. 2013 Biochemistry Discussion HIV S375A 85 90 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. To test this we probed the interactions of a PT variant with a C-terminal biotin (KR21) with the gp120 mutant S375A using SPR. 2013 Biochemistry Discussion HIV S375A 110 115 gp120 97 102 23470147 A model of peptide triazole entry inhibitor binding to HIV-1 gp120 and the mechanism of bridging sheet disruption. We think the lower potency of KR21 for S375A argues for the role of a direct contact effect in this case and possibly a combination of direct contact and conformational alteration for S375W. 2013 Biochemistry Discussion HIV S375A;S375W 39;184 44;189 23533419 Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans. In contrast, no combination of the mutations in folP from isolate 797 (A46V, E80K, Q122H, and S146G) led to differences in susceptibility of folP knockout bacteria to sulfonamide. 2013 International journal of microbiology Discussion HIV A46V;E80K;Q122H;S146G 71;77;83;94 75;81;88;99 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Both of these bcn Envs were far superior to CM243(N610Q). 2013 PloS one Discussion HIV N610Q 50 55 Env 18 22 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. However, we have not been able to demonstrate increased sensitivity to neutralization of CM243(N610Q) by any cross neutralizing mAbs, and have no present hypothesis regarding the mechanism of this apparent increased immunogenicity. 2013 PloS one Discussion HIV N610Q 95 100 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. One particular Env, CM243(N610Q), was selected on the basis of results presented here which demonstrated that a mutation that eliminated an N-linked glycosylation site in gp41 proximal to the disulfide-bonded loop resulted in enhanced capacity to induce neutralizing antibodies in rabbits. 2013 PloS one Discussion HIV N610Q 26 31 gp41;Env 171;15 175;18 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. Since a murine mAb had been identified in a previous study that had weak neutralizing activity and bound very close to the gp41 disulfide-bonded loop, the effects of the two mutations closest to the loop, N610Q and N615Q, on induction of neutralizing antibody were studied. 2013 PloS one Discussion HIV N610Q;N615Q 205;215 210;220 gp41 123 127 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The 14/00/4 Env induced neutralizing antibodies that were somewhat less cross-reactive than those induced by R2, and the CM243(N610Q) Env induced little neutralizing cross-reactivity among neutralization resistant strains. 2013 PloS one Discussion HIV N610Q 127 132 Env;Env 12;134 15;137 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The potential for additive effects of multiple substitutions was studied by comparing the effects of each of those mutations separately and combined, as well as the quadruple mutant, N610Q/N615Q/N624Q/N636Q. 2013 PloS one Discussion HIV N610Q;N615Q;N624Q;N636Q 183;189;195;201 188;194;200;206 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. The wild type CM243 Env did not induce homologous neutralizing antibodies in rabbits, when administered as soluble protein in adjuvant, but the N610Q mutant was immunogenic. 2013 PloS one Discussion HIV N610Q 144 149 Env 20 23 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. These two Envs were tested in parallel with the CM243(N610Q) Env in rhesus monkeys. 2013 PloS one Discussion HIV N610Q 54 59 Env;Env 10;61 14;64 23533650 Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins. We found that the N610Q mutant protein did induce neutralizing antibodies in rabbits, while the N615Q mutant did not, and the double and quadruple mutants were no more effective at inducing neutralizing antibodies than the single N610Q gp140 mutant. 2013 PloS one Discussion HIV N610Q;N610Q;N615Q 18;230;96 23;235;101 gp140 236 241 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. Another interesting observation was the substitution of a phosphorylable serine residue to alanine in cytoplasmic helix-2 in all of the group B variants (S61A). 2013 PloS one Discussion HIV S61A 154 158 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. It is noteworthy that despite exhibiting extensive polymorphisms (deletion in transmembrane domain as well as numerous point mutations), S61A mutants from group B Vpu variants showed enhanced intracellular expression and intracellular stability. 2013 PloS one Discussion HIV S61A 137 141 Vpu 163 166 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. The intracellular stability of S61A mutants correlated with their ubiquitination profile as S61A mutants exhibited significantly less ubiquitination than S61 wt variants. 2013 PloS one Discussion HIV S61A;S61A 31;92 35;96 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. The reduced viral release activity observed in S61A variant Vpu 7 on the other hand could be explained because of the presence of long transmembrane deletion that seriously affected viral release process. 2013 PloS one Discussion HIV S61A 47 51 Vpu 60 63 23555649 Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death. We therefore verified whether our natural S61A mutants possessing additional numerous variations (including transmembrane deletions) in cytoplasmic regions, displayed greater kinetic stability. 2013 PloS one Discussion HIV S61A 42 46 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Additional experimental studies of others have also upheld the insights from MD simulations, showing an increase in protein stability after combining A71V to a primary mutation. 2013 Biochemistry Discussion HIV A71V 150 154 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Additionally, MD simulations have shown that M36I decreases the binding cavity volume. 2013 Biochemistry Discussion HIV M36I 45 49 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Additionally, the closed-like conformation dominates with A71V alone or in combination with M36I. 2013 Biochemistry Discussion HIV A71V;M36I 58;92 62;96 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Although NMR investigations reveal differences in D25 versus D25N dynamics and monomer/dimer dissociation constants, our data for the D25N constructs do show strong correlations among DEER distance profiles and in vitro kinetic/inhibition data. 2013 Biochemistry Discussion HIV D25N;D25N 61;134 65;138 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. DEER samples contain the K55R1 spin-label site and the catalytic residue substitution D25N. 2013 Biochemistry Discussion HIV D25N 86 90 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Figures 6A and 6B provide a graphical interpretation of the results of our population analyses for WT subtype B and D30N/M36I/A71V constructs; respectively, in terms of hypothetical thermodynamic profiles. 2013 Biochemistry Discussion HIV A71V;D30N;M36I 126;116;121 130;120;125 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. However, we find herein that the M36I mutation alone has only a minimal effect on the conformational sampling ensemble compared to native enzyme. 2013 Biochemistry Discussion HIV M36I 33 37 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Interestingly, for the triple mutation construct, D30N/M36I/A71V, the substrate mimic CA-p2 induced flap closure, but not RTV. 2013 Biochemistry Discussion HIV A71V;D30N;M36I 60;50;55 64;54;59 Capsid 86 88 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Perhaps the thermodynamic stabilizing effects of A71V come about by a structural shift to a closed-like state as the predominant conformer of the equilibrium ensemble. 2013 Biochemistry Discussion HIV A71V 49 53 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Previous X-ray crystal structure and MD investigations of the A71V polymorphism show that this substitution requires a local structural adjustment in the cantilever region, particularly amino acid residues 67-71, to accommodate the bulkier valine side-chain. 2013 Biochemistry Discussion HIV A71V 62 66 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Recent MD simulations also indicate that A71V may stabilize the dimeric form of the enzyme, which could be essential to offset effects of other mutations that alter beta-hairpin conformation and destabilize the dimer interface. 2013 Biochemistry Discussion HIV A71V 41 45 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Strikingly, on the other hand, when either A71V or M36I is combined with D30N, a closed-like conformer dominates the ensemble, with less than 35% occupancy of the semi-open conformation. 2013 Biochemistry Discussion HIV A71V;D30N;M36I 43;73;51 47;77;55 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The D25N mutation has been shown to not significantly change the protein structure, although, it does increase inhibitor dissociation (Kd) by up to a factor of ~106. 2013 Biochemistry Discussion HIV D25N 4 8 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The D30N/M36I/A71V construct has been reported to have weaker inhibition (higher Ki) for nelfinavir, indinavir, and ritonavir, and better catalytic efficiency with respect to WT. 2013 Biochemistry Discussion HIV A71V;D30N;M36I 14;4;9 18;8;13 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The experimental ease of using the D25N constructs has been validated in our earlier SDSL EPR investigations showing correlations among inhibitor-induced flap closure with NMR investigated ligand-exchange dynamics and with IC50 values for a multidrug resistant HIV-1 PR construct. 2013 Biochemistry Discussion HIV D25N 35 39 PR 267 269 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The lack of correlation between %C and Km is not surprising given only D30N occurs within the active site pocket and crystal structures show that the incorporation of A71V along with D30N does not alter the shape of the substrate binding pocket (Supporting Information). 2013 Biochemistry Discussion HIV A71V;D30N;D30N 167;71;183 171;75;187 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The ligand-bound DEER distance profiles in Figure 4 suggest that both the substrate mimic, CA-p2 and ritonavir could efficiently induce a shift in the conformational ensemble to the closed state of D30N, M36I and A71V single point mutation constructs. 2013 Biochemistry Discussion HIV A71V;D30N;M36I 213;198;204 217;202;208 Capsid 91 93 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. The same flap distance of ~33 A observed for the closed-like state in the apoenzyme and the closed conformation upon inhibitor binding suggests that these states are indistinguishable and validates that the incorporation of a single point A71V mutation results in promoting the closed flap conformation. 2013 Biochemistry Discussion HIV A71V 239 243 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. Unlike D30N and M36I, the A71V construct has a predominant closed-like population in the apo state. 2013 Biochemistry Discussion HIV A71V;D30N;M36I 26;7;16 30;11;20 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. When compared to WT, incorporation of the D30N primary mutation does not significantly alter the conformational sampling profile, where roughly 65-70% of the conformers populate a semi-open state (Figure 3B). 2013 Biochemistry Discussion HIV D30N 42 46 23566104 Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease. When M36I and A71V secondary polymorphisms are combined with primary mutation D30N, the fractional occupancy resembles that of native enzyme in that the semi-open state now becomes the most predominant conformation in the ensemble. 2013 Biochemistry Discussion HIV A71V;D30N;M36I 14;78;5 18;82;9 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). Indeed, the most commonly occurring mutation in our study was the NNRTI mutation K103N, which was the only mutation present in virus from 14 women; an additional 5 women had HIV with K103N and other NRTI or NNRTI mutations. 2013 PloS one Discussion HIV K103N;K103N 81;183 86;188 NNRTI;NNRTI;NRTI 66;207;199 71;212;203 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). Possible sources of K103N acquisition include transmission from a partner on first line therapy in South Africa which includes nevirapine or efavirenz, or selection of resistance from prior exposure to nevirapine for prevention of mother to child transmission (PMTCT). 2013 PloS one Discussion HIV K103N 20 25 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). Several studies have indicated that K65R may be more readily selected in subtype C virus, or may be polymorphic at low frequencies. 2013 PloS one Discussion HIV K65R 36 40 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). The frequency of K65R may change over time with increased tenofovir use for first-line HIV treatment. 2013 PloS one Discussion HIV K65R 17 21 23585827 Prevalence of HIV-1 drug resistance among women screening for HIV prevention trials in KwaZulu-Natal, South Africa (MTN-009). This may explain why the frequency of resistance with K65R was found to be low (<1%) in this study. 2013 PloS one Discussion HIV K65R 54 58 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. Preventing the L10F mediated breakage of the ion pair between Arg8/8' and Asp29'/29 may be important for stronger inhibition of PR20. 2013 Journal of medicinal chemistry Discussion HIV L10F 15 19 Asp;PR 74;128 77;130 23590295 Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran. The insertion between L10F and Arg8 of the P2 group of saquinavir from the second binding site in the PR20/saquinavir complex may suggest a possible approach to overcome the effects of the L10F mutation. 2013 Journal of medicinal chemistry Discussion HIV L10F;L10F 22;189 26;193 PR 102 104 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. A high frequency of minor PI resistance mutations (M36I, L63P, and K20R/I) has been reported in newly diagnosed immigrants from Spain, infected with non-B subtypes. 2013 Journal of medical virology Discussion HIV K20I;K20R;L63P;M36I 67;67;57;51 73;73;61;55 PI 26 28 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. An in vivo fitness cost associated with the M184V/I mutation has been previously shown in patients naive to antiretroviral therapy. 2013 Journal of medical virology Discussion HIV M184I;M184V 44;44 51;51 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. Four TAMs in combination with M184V cause high-level resistance to both ABC and ddI. 2013 Journal of medical virology Discussion HIV M184V 30 35 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The E138A-RT mutation, a polymorphism that has been added recently to the list of mutations associated with decreased etravirine response was recorded in the study group. 2013 Journal of medical virology Discussion HIV E138A 4 9 RT 10 12 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The most common accessory PI resistance mutation observed in this study was M36I, and this has been reported to increase viral fitness and confer resistance to ritonavir and nelfinavir. 2013 Journal of medical virology Discussion HIV M36I 76 80 PI 26 28 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The next most frequent mutation was M184V, which confers high-level resistance to lamivudine and emtricitabine. 2013 Journal of medical virology Discussion HIV M184V 36 41 23592112 Transmitted HIV drug resistance in treatment-naive Romanian patients. The phenotypic and clinical significance of M184V is influenced by the presence or absence of other NRTI resistance mutations. 2013 Journal of medical virology Discussion HIV M184V 44 49 NRTI 100 104 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Alternatively, the enhanced neutralization of T138N and DeltaN139INN by 2G12 may be a result of changes in the global antigenic structure of gp120-gp41, as was suggested by the finding that the V1 glycan deletions slightly enhanced the neutralization potency of polyclonal HIVIG. 2013 PLoS pathogens Discussion HIV T138N 46 51 gp120;gp41 141;147 146;151 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. Cell-cell fusion and viral replication were also restored by a short DeltaN139INN deletion in V1 operating in conjunction with a D601N pseudoreversion. 2013 PLoS pathogens Discussion HIV D601N 129 134 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. For example, T138N/L494I rendered subunit association and fusion function largely independent of Leu593 and Lys601, whereas less dependence on Lys601 was observed with DeltaN139INN. 2013 PLoS pathogens Discussion HIV L494I;T138N 19;13 24;18 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. However, DeltaN139INN/K601N-mediated cell-cell fusion and virus infectivity were more resistant to sCD4 inhibition suggesting that the conformation of the DeltaN139INN/K601N Env trimer is subtly different to that of WT and T138N/L494I/K601N. 2013 PLoS pathogens Discussion HIV K601N;L494I;T138N;K601N;K601N 235;229;223;22;168 240;234;228;27;173 Env 174 177 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. In the case of W596L, T138N and DeltaN139INN were sufficient to confer WT fusion levels, but this did not involve changes to the WT-like gp120-gp41 association phenotype of W596L. 2013 PLoS pathogens Discussion HIV T138N;W596L;W596L 22;15;173 27;20;178 gp120;gp41 137;143 142;147 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. In this study, we forced the evolution of a DSR mutant (K601D) with defective gp120-gp41 association, reasoning that the locations of emergent 2nd site mutations that suppress the defect will point to structural elements within gp120-gp41 with functional links to the DSR. 2013 PLoS pathogens Discussion HIV K601D 56 61 gp120;gp120;gp41;gp41 78;228;84;234 83;233;88;238 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. It may be that the apparently looser association between gp120 and gp41 of DeltaN139INN/K601N alters the conformational pathway of the sCD4-induced state to enable maintenance of fusion competence. 2013 PLoS pathogens Discussion HIV K601N 88 93 gp120;gp41 57;67 62;71 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. One mechanism of reversion involved the acquisition of L494I in C5 that led to slightly improved gp120-gp41 association and fusion function with Asp601, but a WT-like phenotype also required deletion of the glycan at Asn136 in V1 through T138N. 2013 PLoS pathogens Discussion HIV L494I;T138N 55;238 60;243 gp120;gp41;Asp 97;103;145 102;107;148 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The AD8 V1V2 model suggests that the Asn142 glycan is proximal to the Asn156 glycan, implying that the N139INN deletion may relieve a steric constraint that enables better epitope access for PG16. 2013 PLoS pathogens Discussion HIV N139I;N139N 103;103 110;110 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The DeltaN139INN/K601N phenotype was largely recapitulated by S144N/K601N, suggesting that loss of the Asn142 glycan is sufficient to restore fusion function when Asn601 is present in the DSR. 2013 PLoS pathogens Discussion HIV K601N;K601N;S144N 17;68;62 22;73;67 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The earlier finding that W596L blocks sCD4-induced formation of the gp41 prehairpin intermediate indicates that Trp596 can play a role in receptor-triggered gp41 activation. 2013 PLoS pathogens Discussion HIV W596L 25 30 gp41;gp41 68;157 72;161 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The fusion gains conferred to W596L may involve transduction of a receptor-induced activation signal from gp120 to gp41 through the association site in manner that is less dependent on Trp596. 2013 PLoS pathogens Discussion HIV W596L 30 35 gp120;gp41 106;115 111;119 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The generation of functional Env complexes with stable gp120-gp41 association following the combination of V1 glycan mutations with various L593V, W596L or K601D DSR mutations, may be mediated by a shifting of the points of intersubunit contact to conserved residues at alternative positions within the synapse [e.g. 2013 PLoS pathogens Discussion HIV K601D;L593V;W596L 156;140;147 161;145;152 gp120;gp41;Env 55;61;29 60;65;32 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The impacts of the V1 glycan changes on the gp120-gp41 association site were probed further by combining T138N, L494I and DeltaN139INN with various DSR mutations: L593V and K601D, which disrupt gp120-gp41 association and fusion function, and W596L which inhibits fusion. 2013 PLoS pathogens Discussion HIV K601D;L494I;L593V;T138N;W596L 173;112;163;105;242 178;117;168;110;247 gp120;gp120;gp41;gp41 44;194;50;200 49;199;54;204 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The loss of glycans at Asn136 or Asn142 within V1, the former acting in conjunction with L494I in C5 and the latter with a D601N pseudoreversion, largely suppressed the functional defects, with Env function becoming less dependent on particular gp120-contact residues (Leu593, Trp596 and Lys601) within the DSR. 2013 PLoS pathogens Discussion HIV D601N;L494I 123;89 128;94 gp120;Env 245;194 250;197 23592978 Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. The most obvious changes due to T138N and DeltaN139INN would be the loss of hydrophilic glycan bulk (~1840 A3 per high-mannose glycan; see) and, for the latter, a shortening of the V1 loop . 2013 PLoS pathogens Discussion HIV T138N 32 37 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Finally, our data corroborated the finding that the restoration of infectivity of L30E viruses by inactivation of Vpu is a universal phenomenon that is occurring in lab-adapted as well as primary cells. 2013 PloS one Discussion HIV L30E 82 86 Vpu 114 117 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Furthermore, we have studied the impact of Vpu inactivation on release and infectivity of Gag MA mutant (L30E). 2013 PloS one Discussion HIV L30E 105 109 Vpu;Gag;Matrix 43;90;94 46;93;96 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Immunostaining data showed increased syncytium formation by double mutant (L30E-DeltaVpu) in MDM as compared to WT and other mutants (Figure 5B). 2013 PloS one Discussion HIV L30E 75 79 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. In addition we observed significant variation between infectivity of DeltaVpu and L30E-DeltaVpu mutants from 293T, NP2 and GHOST cells. 2013 PloS one Discussion HIV L30E 82 86 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Initially, we failed to observe difference in infectivity potential of DeltaVpu and L30E-DeltaVpu mutants from HeLa cells. 2013 PloS one Discussion HIV L30E 84 88 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Intriguingly, by contrast to what was observed with Gag L30E viruses, in which infectivity of viruses was severely abrogated due to reduced Env incorporation, we observed significant restoration of infectivity of L30E viruses in absence of Vpu (Figure 3B). 2013 PloS one Discussion HIV L30E;L30E 56;213 60;217 Vpu;Env;Gag 240;140;52 243;143;55 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Knockdown of endogenous BST-2 revealed that silencing of BST-2 in HeLa cells not only increased the production of DeltaVpu viruses but also enhanced the infectivity of double mutant (L30E-DeltaVpu) viruses compared to L30E and DeltaVpu viruses. 2013 PloS one Discussion HIV L30E;L30E 183;218 187;222 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. Moreover, in contrast to L30E and DeltaVpu mutant viruses, double-mutant (L30E-DeltaVpu) viruses replicated efficiently in primary cells (PBMC and MDM) also. 2013 PloS one Discussion HIV L30E;L30E 25;74 29;78 23613843 Evidence that Vpu modulates HIV-1 Gag-envelope interaction towards envelope incorporation and infectivity in a cell type dependent manner. We show here that the inactivation of Vpu by start codon mutation rescued the infectivity defect of Gag mutant (L30E) viruses by enhancing Env incorporation on released virion particles. 2013 PloS one Discussion HIV L30E 112 116 Vpu;Env;Gag 38;139;100 41;142;103 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Alternatively, the membrane perturbing properties of the MPER may be enhanced by D674E. 2013 Retrovirology Discussion HIV D674E 81 86 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. In a second culture, revertant clones contained the DeltaT394-W395 deletion in V4 in addition to D601H and D674N. 2013 Retrovirology Discussion HIV D601H;D674N 97;107 102;112 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. In this case, the D601H mutation would also restore positive charge to position 601, which may also lend stability to the gp120-gp41 association site. 2013 Retrovirology Discussion HIV D601H 18 23 gp120;gp41 122;128 127;132 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Interestingly, the addition of D674E to W596L/K601H only marginally improved gp120-association for cell-free virions whereas single-cycle infectivity was improved some 20-fold. 2013 Retrovirology Discussion HIV D674E;K601H;W596L 31;46;40 36;51;45 gp120 77 82 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. It is also possible that D674E directly enhances an MPER-related function in virus-cell fusion. 2013 Retrovirology Discussion HIV D674E 25 30 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. It is interesting that the boosts to infectivity associated with the addition of D674E to W596L/K601H did not correlate with enhanced cell-cell fusion activity, where the cell-surface expressed glycoproteins function independently of other virion components. 2013 Retrovirology Discussion HIV D674E;K601H;W596L 81;96;90 86;101;95 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. It may be that increased MPER hinge flexibility due to D674E relieves or corrects a structural constraint on WL/KH-containing Env to enable stronger gp120-gp41 association within the virion glycoprotein complex, thereby enhancing entry function. 2013 Retrovirology Discussion HIV D674E 55 60 gp120;gp41;Env 149;155;126 154;159;129 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Phenotypic analysis of the revertant genotypes indicated that D601H is a key evolutionary step that partially restores gp120-gp41 association. 2013 Retrovirology Discussion HIV D601H 62 67 gp120;gp41 119;125 124;129 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The boost to the infectivity of WL/KH cell-free virus upon addition of D674E may therefore be related to increased MPER flexibility. 2013 Retrovirology Discussion HIV D674E 71 76 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The combination of His-601 with D674E led to improved single-cycle and multi-cycle cell-free virus-initiated infectivity without detectable further improvement in gp120-gp41 association. 2013 Retrovirology Discussion HIV D674E 32 37 gp120;gp41 163;169 168;173 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The forced evolution of WL/KD mutant viruses with severely disrupted gp120-gp41 association led to the emergence of replication-competent revertants containing a D601H pseudoreversion in the DSR plus D674E or D674N 2nd site mutations in the MPER. 2013 Retrovirology Discussion HIV D601H;D674E;D674N 162;200;209 167;205;214 gp120;gp41 69;75 74;79 23618462 Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. The HR1 of gp41 is implicated as one such element by the finding that T569A (HR1) and I675V (MPER) polymorphisms synergize in conferring a neutralization sensitive Env conformation. 2013 Retrovirology Discussion HIV I675V;T569A 86;70 91;75 gp41;Env 11;164 15;167 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. In contrast, the DA uptake potency of cocaine and GBR12909 is increased in Y470H-hDAT compared to WT hDAT. 2013 Journal of neuroimmune pharmacology Discussion HIV Y470H 75 80 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Interestingly, the magnitude of DA efflux in WT hDAT was lower in response to Tat compared to that in Y470H-hDAT. 2013 Journal of neuroimmune pharmacology Discussion HIV Y470H 102 107 Tat 78 81 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. Thus, it is possible that Y470H mutation shifts the conformation of DAT from physiologically favored substrate influx mode to an efflux one; a conformational switch promoted by Tat protein, and disturbs transition between inward- and outward-facing conformations. 2013 Journal of neuroimmune pharmacology Discussion HIV Y470H 26 31 Tat 177 180 23645138 Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. To explore the possible mechanism, we also examined the effects of mutant hDAT on basal DA efflux and observed extremely low accumulation of DA over time in Y470H-hDAT relative to WT hDAT. 2013 Journal of neuroimmune pharmacology Discussion HIV Y470H 157 162 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. Activity tests done on D64V-IN variants produced in E. 2013 PloS one Discussion HIV D64V 23 27 IN 28 30 23667513 Consensus HIV-1 FSU-A integrase gene variants electroporated into mice induce polyfunctional antigen-specific CD4+ and CD8+ T cells. For HIV-1 clade A, the main mutations of elvitegravir resistance are H51Y, E92Q, S147G, along with E157Q and a secondary nonpolymorphic mutation, K160Q, highly infrequent in integrase inhibitor-naive patients; introduction of these mutations generated IN derivative IN_in_e3. 2013 PloS one Discussion HIV E157Q;E92Q;H51Y;K160Q;S147G 99;75;69;146;81 104;79;73;151;86 IN;IN 174;252 183;254 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Although there was a high frequency (7/39) of PI substitutions (including L33I/F and L90M, which we did not observe) in this subgroup, many patients were on NRTI-sparing dual-PI regimens and it is not possible to assess whether the substitutions observed were selected by atazanavir or by the other PI in the regimen. 2013 The Journal of antimicrobial chemotherapy Discussion HIV L33F;L33I;L90M 74;74;85 80;80;89 NRTI;PI;PI;PI 157;46;175;299 161;48;177;301 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. However, there was an increased frequency of several other mutations, including I15S, L19T, K43T, L63P/V, K70Q and L89I/T/V, which are not recognized to be associated with atazanavir by the most recent IAS classification. 2013 The Journal of antimicrobial chemotherapy Discussion HIV I15S;K43T;K70Q;L19T;L63P;L63V;L89I;L89T;L89V 80;92;106;86;98;98;115;115;115 84;96;110;90;104;104;123;123;123 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Our findings show that very few patients failing a therapy containing atazanavir are likely to have developed one of the major protease resistance mutations (I50L, I84V and N88S) that confer high-level phenotypic resistance to this drug. 2013 The Journal of antimicrobial chemotherapy Discussion HIV I50L;I84V;N88S 158;164;173 162;168;177 PR 127 135 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. They described eight mutations that had an adverse effect on viral load reduction at 3 months, but only two of these (M46I and I84V) coincided with those identified in our analysis. 2013 The Journal of antimicrobial chemotherapy Discussion HIV I84V;M46I 127;118 131;123 23711895 Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study. Two other mutations, K43T and L89V, have previously been shown to decrease susceptibility to PIs in combination with other mutations. 2013 The Journal of antimicrobial chemotherapy Discussion HIV K43T;L89V 21;30 25;34 PI 93 96 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. However, the resistance to neutralization by gp41 truncation was shown using the E767stop mutant of SIVmac316. 2013 Frontiers in microbiology Discussion HIV E767X 81 89 gp41 45 49 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. In the present study, truncation of the cytoplasmic tail of gp41, which was caused by the Q733stop substitution in Env, was the first major mutation detected during passage of SIV in the presence of the neutralizing antibody B404. 2013 Frontiers in microbiology Discussion HIV Q733X 90 98 gp41;Env 60;115 64;118 23717307 Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail. This is consistent with our results using SIVmac316 harboring the Q733stop substitution, indicating that gp41 truncation contributes to resistance of SIVmac316 to neutralization. 2013 Frontiers in microbiology Discussion HIV Q733X 66 74 gp41 105 109 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. For transmitted NRTI-resistance, the low presence found (with the predominance of change M184V) agrees with the study of Djoko et al., although they only found the substitution D67N as transmitted NRTI-resistance mutation. 2013 PloS one Discussion HIV D67N;M184V 177;89 181;94 NRTI;NRTI 16;197 20;201 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. The highest TDR rate was found for PI (3.4%), led by the presence of the substitution M46I/L in all cases. 2013 PloS one Discussion HIV M46I;M46L 86;86 92;92 PI 35 37 23717585 Description of HIV-1 group M molecular epidemiology and drug resistance prevalence in Equatorial Guinea from migrants in Spain. Thus, the PI-resistance mutation M46L, present in all subtype B viruses with TDR ( Table 5 ), was rare (<1%) among the subtype B-infected population living in Spain, where L90M was predominant. 2013 PloS one Discussion HIV L90M;M46L 172;33 176;37 PI 10 12 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. On-going exposure to thymidine NRTIs, including d4T and azidothymidine (AZT), in the setting of on-going viral replication contributed to further accumulation of K65R and TAMs, resulting in substantial levels of resistance to tenofovir. 2013 Journal of the International AIDS Society Discussion HIV K65R 162 166 NRTI 31 36 23735817 Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India. Subtype C HIV-1 virus is predominant in India, and it has been previously established that in this subtype, K65R is selected for by on-going exposure to d4T and leads to tenofovir cross-resistance. 2013 Journal of the International AIDS Society Discussion HIV K65R 108 112 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. Although the two compounds showed different modes of binding from those of WT complex, their binding energies were do not significantly changed (Table 1) except for N224H-M522 system. 2013 Bioinformation Discussion HIV N224H 165 170 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. Due to steric constraint of imidazole side chain of His, the mutation of S217H leads to inhibitor binding in another region that is different from those of WT and the other two mutant systems. 2013 Bioinformation Discussion HIV S217H 73 78 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. However, from our docking calculation, although the mutation of Y212R was observed to destroy the pi-pi stacking interaction between protein and ligand, other types of interaction i.e. 2013 Bioinformation Discussion HIV Y212R 64 69 PI;PI 98;101 100;103 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. In the WT structure, the side chain of Tyr143 was found to form a direct pi-pi stacking interaction with oxadiazole ring of raltegravir, however, the replacement of Tyr by Arg (Y143R) disturbs this type of interaction, thereby could possible significantly influence drug inhibitory potency . 2013 Bioinformation Discussion HIV Y143R 177 182 PI;PI 73;76 75;78 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. Our docking analysis suggested that M532 might be active against the mutation of N224H IN (corresponding to N155H HIV-1 IN). 2013 Bioinformation Discussion HIV N155H;N224H 108;81 113;86 IN;IN 87;120 89;122 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The docking results of the N224H mutant revealed that the bound conformations of both M522 and M532 were also different from those of WT complex. 2013 Bioinformation Discussion HIV N224H 27 32 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The hypothetically predicted mode of action of these two compounds against the Y212R (corresponding to Y143R HIV-1 IN) and N224H (corresponding to N155H HIV-1 IN) PFV IN are displayed in (Figures 3B & 3C), respectively. 2013 Bioinformation Discussion HIV N155H;N224H;Y143R;Y212R 147;123;103;79 152;128;108;84 IN;IN;IN 115;159;167 117;161;169 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The mutation strain of G140S/Q148H in HIV-1 IN has > 150-fold reduced susceptibility to raltegravir . 2013 Bioinformation Discussion HIV G140S;Q148H 23;29 28;34 IN 44 46 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The predicted binding modes of both M522 and M532 with the S209/S217H mutant (equivalent to G140S/Q148H HIV-1 IN) are displayed in Figure 3D. 2013 Bioinformation Discussion HIV S217H;G140S;Q148H 64;92;98 69;97;103 IN 110 112 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. The proposed raltegravir resistance pathway of the less frequently Y143H/R/C has been directly related to the interaction between inhibitor and Tyr143. 2013 Bioinformation Discussion HIV Y143C;Y143H;Y143R 67;67;67 76;76;76 23750093 Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor. This is different in the case of M522 and M532, Although the mutation of S217H (corresponding to G140S/Q148H of HIV-1 IN) disturbed the inhibitor binding mode, it is likely that both compounds were capable to preserve the main interactions with Mg2+ ions, the contacting amino acids and viral DNA. 2013 Bioinformation Discussion HIV G140S;Q148H;S217H 97;103;73 102;108;78 IN 118 120 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. A longer time on ART may lead to an increase in K65R, especially if patients with virologic failure were maintained on a failing regimen for an extended period of time. 2013 Antiviral therapy Discussion HIV K65R 48 52 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Another approach is to include the low-level K65R mutants detected by AS-PCR, making the assumption that these minority quasi-species were on the way to becoming dominant and were not detected by our consensus sequencing. 2013 Antiviral therapy Discussion HIV K65R 45 49 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Another possibility could be the use of alternative resistance pathways that may have antagonism toward the K65R, such as TAMS and the K70E. 2013 Antiviral therapy Discussion HIV K65R;K70E 108;135 112;139 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Despite these limitations, we believe our analysis provides additional valuable information on K65R development in subtype C HIV. 2013 Antiviral therapy Discussion HIV K65R 95 99 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. For patients without prior ART exposure we did not identify any K65R mutations by population sequencing; while re-assuring that this mutation does not appear to develop rapidly, our small sample size and relatively short duration of failure requires circumspection. 2013 Antiviral therapy Discussion HIV K65R 64 68 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. However, only four patients developed TAMs and0 no K70E mutations were detected by either population sequencing or AS-PCR, making this an unlikely explanation. 2013 Antiviral therapy Discussion HIV K70E 51 55 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. In our cohort of patients with subtype C HIV who were receiving regular HIV RNA monitoring while on a TDF-containing ART, NNRTI and M184V mutations predominated while resistance to TDF occurred less frequently. 2013 Antiviral therapy Discussion HIV M184V 132 137 NNRTI 122 127 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Indeed, it appeared that prior d4T use was a risk for the K65R mutation in this cohort, possibly because the mutation was already being selected during prior d4T use. 2013 Antiviral therapy Discussion HIV K65R 58 62 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. It is unclear how this affected our results; however, if d4T did select for the K65R mutation, we may have overestimated the effect of TDF on K65R prevalence. 2013 Antiviral therapy Discussion HIV K65R;K65R 80;142 84;146 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Notably, our results are consistent with a modest increase in K65R associated with subtype C HIV, similar to the 16% prevalence reported in a multi-national analysis of subtype C HIV and with overlapping confidence intervals with another study in Africa in which 27.7% of the 47 participants receiving TDF developed the K65R mutation. 2013 Antiviral therapy Discussion HIV K65R;K65R 62;320 66;324 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Our overall finding of a moderately higher prevalence of the K65R mutation among patients with subtype C HIV and virologic failure on a TDF-containing regimen adds to evidence for differences in the development of HIV drug resistance by HIV-1 genotype but is also re-assuring in that we did not find a markedly higher prevalence of the K65R that could have greater clinical importance. 2013 Antiviral therapy Discussion HIV K65R;K65R 61;336 65;340 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. The K65R mutation was present among 12% (confidence interval of 4.1 - 27) of individuals at first detection of virologic failure of a TDF-containing regimen. 2013 Antiviral therapy Discussion HIV K65R 4 8 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. This increased the K65R proportion to 5/22 (23%). 2013 Antiviral therapy Discussion HIV K65R 19 23 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. This prevalence is similar to some prior studies based in clinical cohorts from subtype C or mixed subtype infections, in which the K65R mutations ranged from 0 to 27% and duration on a TDF-containing regimen ranged from 324 to 1000 days . 2013 Antiviral therapy Discussion HIV K65R 132 136 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. To further assess the prevalence of K65R with this scenario, we excluded patients without resistance mutations and only included the 22 patients with any mutations. 2013 Antiviral therapy Discussion HIV K65R 36 40 23751421 Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa. Where this occurred, some of the identified mutations, including K65R, may have developed during d4T exposure. 2013 Antiviral therapy Discussion HIV K65R 65 69 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. After 17 passages, they found pseudoviruses containing the polymorphism F317W (F312W from the V3 library) with typical non-competitive resistance to MVC. 2013 AIDS research and therapy Discussion HIV F312W;F317W 79;72 85;77 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. described HIV-1 CCR5 ( Nt)-adapted mutants of the JR-CSF strain that had mutations in regions V3, V2 and C3 with 4 mutations in the V4 loop: N403S, N403K, T405A, and T405N. 2013 AIDS research and therapy Discussion HIV N403K;N403S;T405A;T405N 148;141;155;166 153;146;160;171 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. In another study, the mutation V169K in V2 was predictive of the R5 phenotype. 2013 AIDS research and therapy Discussion HIV V169K 31 36 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. In our study, I408T in V4 was the mutation that conferred the highest level of resistance. 2013 AIDS research and therapy Discussion HIV I408T 14 19 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. In their study, R5 isolates harboring 2 dominant polymorphisms, R315Q and F317W in V3, were less susceptible than B isolates to MVC and TAK779. 2013 AIDS research and therapy Discussion HIV F317W;R315Q 74;64 79;69 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. In their study, the mutation V169T showed strong association with CXCR4 usage while V169K was coupled with CCR5 usage. 2013 AIDS research and therapy Discussion HIV V169K;V169T 84;29 89;34 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Interestingly, when V3 substitution L317W is associated with V4 substitution I408T or triple substitution V169M/L317W/I408T, it confers further reduction of infectivity to 70% of the parental clone (Figure 2). 2013 AIDS research and therapy Discussion HIV I408T;L317W;V169M;I408T;L317W 118;112;106;77;36 123;117;111;82;41 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Our passage experiments revealed only 1 polymorphism in the V3 loop crown, L317W, which was associated with reduced infectivity, but not with resistance to CCR5 inhibitors or changes in V3 net charge (Tables 1 and 2). 2013 AIDS research and therapy Discussion HIV L317W 75 80 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Our results disclosed that mutant V169M exploits R5 exclusively as a co-receptor. 2013 AIDS research and therapy Discussion HIV V169M 34 39 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. Since positions 403 and 408 of the V4 loop are close proximity, we imagine that the resistance conferred by I408T mutation in our study could alter the quaternary structure of the HIV-1 Env, thus sterically masking the glycosylation site in position 403. 2013 AIDS research and therapy Discussion HIV I408T 108 113 Env 186 189 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. The mutation V169M, identified in our study, was also found by Marozsan et al. 2013 AIDS research and therapy Discussion HIV V169M 13 18 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. The polymorphism F317W was also found by Munoz-Nieto et al. 2013 AIDS research and therapy Discussion HIV F317W 17 22 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. The V4 mutations consisted of D407G and loss of a glycosylation site at residue 386. 2013 AIDS research and therapy Discussion HIV D407G 30 35 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. This decreased infectivity could be due to lower fusion activity or binding affinity to the CCR5 co-receptor molecule of the mutant L317W. 2013 AIDS research and therapy Discussion HIV L317W 132 137 23758814 Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. V169M mutation was coupled with reduced infectivity but not with a resistant phenotype. 2013 AIDS research and therapy Discussion HIV V169M 0 5 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Electron microscopic analysis of mutant particles indicated that H12Y and Q137R mutants have highly aberrant virion morphology. 2013 Retrovirology Discussion HIV H12Y;Q137R 65;74 69;79 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. For example, S147G, a partially defective mutant showed slow replication in the first round of replication in a multiday replication assay. 2013 Retrovirology Discussion HIV S147G 13 18 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Furthermore, in a report using C130S IN mutation it was demonstrated that capsid was unstable, but the morphology of the mutant capsid was not described. 2013 Retrovirology Discussion HIV C130S 31 36 Capsid;Capsid;IN 74;128;37 80;134;39 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Interestingly, both S147G and K111E retain their in vitro integration activity, while the highly defective mutants either did not express stable proteins in bacteria or were defective for integration activity (data not shown). 2013 Retrovirology Discussion HIV K111E;S147G 30;20 35;25 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. K71R, on the other hand, appears to have an overall low level of DNA synthesis. 2013 Retrovirology Discussion HIV K71R 0 4 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. One of the mutants recovered during our reverse two hybrid screen was K71R; this mutant was previously identified as an INI1-interaction defective mutant of IN. 2013 Retrovirology Discussion HIV K71R 70 74 IN;IN;IN 120;120;157 123;124;159 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Our observation indicates that the degree of IN-INI1 binding correlates well with the level of viral replication, in that mutants H12Y, Q137R and D202G, severely impaired for INI1 binding, are dramatically impaired for replication in both multi- and single-cycle infection assays (Figure 2). 2013 Retrovirology Discussion HIV D202G;H12Y;Q137R 146;130;136 151;134;141 IN;IN;IN;IN;IN 48;175;45;48;175 51;178;47;52;179 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Our results indicate an interesting trend with respect to late RT step with the mutants H12Y, Q137R and D202G. 2013 Retrovirology Discussion HIV D202G;H12Y;Q137R 104;88;94 109;92;99 RT 63 65 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Partially defective IID-IN mutants, S147G, and K111E were less defective for reverse transcription and 2LTR circle formation, suggesting that partial retention of INI1 binding is enough to proceed through these steps. 2013 Retrovirology Discussion HIV K111E;S147G 47;36 52;41 RT;IN;IN;IN 77;163;24;163 98;166;26;167 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Sequence analysis of the virions from this culture indicated that S147G virus has reverted to true wild type (data not shown). 2013 Retrovirology Discussion HIV S147G 66 71 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. This study indicated that K71R mutant was more replication competent than wild type. 2013 Retrovirology Discussion HIV K71R 26 30 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. While H12Y mutants exhibit immature virion morphology, Q137R and D202 virions exhibit varying degree of defects in morphology and accumulate mixture of virions that have acentric crescent shaped, or immature or aberrant cores (Figure 5). 2013 Retrovirology Discussion HIV H12Y;Q137R 6;55 10;60 23799881 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. While Q137R exhibits defect in several protein-protein interactions, D202G is not significantly defective for interaction with WT IN or with the other known IN-binding proteins tested (LEDGF, SAP18, GEMIN2 or RT, Figure 7), but is severely defective for binding to INI1 (Figure 1). 2013 Retrovirology Discussion HIV D202G;Q137R 69;6 74;11 IN;IN;IN;IN;RT 265;130;157;265;209 268;132;159;269;211 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. A decreased unblocking of EFdA-MP-terminated primers is not due to their inability to bind at the excisable N site of K65R RT. 2013 Retrovirology Discussion HIV K65R 118 122 RT 123 125 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Hence, we investigated the effect of the K65R mutation on translocation using the site-specific Fe2+ footprinting assay. 2013 Retrovirology Discussion HIV K65R 41 45 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. In addition, we have previously reported that K65R and L74V HIVs can be hypersusceptible to NRTIs with 4'-ethynyl substitutions. 2013 Retrovirology Discussion HIV K65R;L74V 46;55 50;59 NRTI 92 97 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. In addition, when we used conditions that more closely mimic cell-based conditions, with ATP as the unblocking reagent and also all dNTPs present in the reaction to extend the unblocked primers, we also found that K65R reduced excision. 2013 Retrovirology Discussion HIV K65R 214 218 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Indeed, our enzymatic assays clearly showed that K65R RT is more susceptible to inhibition by EFdA-TP than WT RT. 2013 Retrovirology Discussion HIV K65R 49 53 RT;RT 54;110 56;112 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. It is associated with the presence of the tenofovir-resistance signature mutation K65R in the reverse transcriptase gene. 2013 Retrovirology Discussion HIV K65R 82 86 RT 94 115 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Moreover, the 3TC/FTC-resistance mutation M184V also increases HIV sensitivity to AZT by decreasing the excision efficiency of AZT-MP. 2013 Retrovirology Discussion HIV M184V 42 47 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Our results showed that the K65R mutation decreased the incorporation efficiencies of EFdA-TP and dATP to the same extent. 2013 Retrovirology Discussion HIV K65R 28 32 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Since the EFdA resistance was not the result of changes in translocation efficiency, we hypothesized that K65R affects either the incorporation of the inhibitor itself, or its excision from EFdA-terminated primers. 2013 Retrovirology Discussion HIV K65R 106 110 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. Specifically, the K65R and to a lesser extent the L74V RT mutations have been reported to suppress AZT resistance. 2013 Retrovirology Discussion HIV K65R;L74V 18;50 22;54 RT 55 57 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The NNRTI-resistance mutation Y181C also increases susceptibility to AZT. 2013 Retrovirology Discussion HIV Y181C 30 35 NNRTI 4 9 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. The present study demonstrates that the K65R tenofovir-resistance RT mutation confers HIV hypersensitivity to EFdA compared to WT HIV. 2013 Retrovirology Discussion HIV K65R 40 44 RT 66 68 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. To determine whether the K65R RT mutation has the same effect at the enzyme level as well, we also carried out inhibitor susceptibility experiments with WT and K65R recombinant RT enzymes. 2013 Retrovirology Discussion HIV K65R;K65R 25;160 29;164 RT;RT 30;177 32;179 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We found that K65R mutation has only a small effect on the translocation state of the EFdA-MP-terminated DNA RT complex suggesting that the EFdA-MP-terminated primers stay at the nucleotide binding site (N site) of K65R RT as much as they do at the N site of WT RT. 2013 Retrovirology Discussion HIV K65R;K65R 14;215 18;219 RT;RT;RT 109;220;262 111;222;264 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We found that K65R reduced excision and kept EFdA-MP-terminated primers blocked, explaining the hypersusceptibility that we have reported. 2013 Retrovirology Discussion HIV K65R 14 18 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We have previously demonstrated that EFdA is highly efficient in suppressing viral replication of clinical isolates harboring signature mutations to other NRTIs and NNRTIs, including isolates containing 3TC/FTC resistance mutation M184V; TAMs or Q151M complex mutations that confer resistance to AZT, d4T, and abacavir; and nevirapine and efavirenz resistance mutations K103N and Y181C. 2013 Retrovirology Discussion HIV K103N;M184V;Q151M;Y181C 370;231;246;380 375;236;251;385 NNRTI;NRTI 165;155 171;160 23800377 Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA. We report here that EFdA is highly potent against tenofovir-resistant K65R HIV, and inhibits this mutant 2.5-fold more efficiently than WT HIV. 2013 Retrovirology Discussion HIV K65R 70 74 23806074 Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. Our results showed that E478Q RT, with a non-functional RNase H, is more sensitive to the commonly used NNRTI antiviral efavirenz than the wild type RT, implying that an active RNase H attenuates drug inhibition. 2013 Biochemistry Discussion HIV E478Q 24 29 NNRTI;RT;RT 104;30;149 109;32;151 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. M46I was identified as a relevant RAM for surveillance of primary HIVDR because it reduces the susceptibility to several PIs even in the absence of other surveillance drug-resistance mutations. 2013 PloS one Discussion HIV M46I 0 4 PI 121 124 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. M46I was the most common RAMs to PIs found in this study, in agreement with reports from Europe and South Africa. 2013 PloS one Discussion HIV M46I 0 4 PI 33 36 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. Previous studies also have shown that K70R has been one of the most common RAMs observed among ART-naive patients, and is consistent with the widespread use of zidovudine and stavudine in the region. 2013 PloS one Discussion HIV K70R 38 42 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. T215D/E/I/S confers an increased risk of virologic failure for ART-naive patients started on regimens including zidovudine or stavudine. 2013 PloS one Discussion HIV T215D;T215E;T215I;T215S 0;0;0;0 11;11;11;11 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. The most common RAM to NNRTIs found in this study was Y181C, which is selected by nevirapine or efavirenz and the most widely used "anchor" drugs in low- and middle-income countries. 2013 PloS one Discussion HIV Y181C 54 59 NNRTI 23 29 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. The mutation selected by lamivudine, M184I/V, and the thymidine analogue mutation of T215D/E/F/I/S/Y were the most common RAMs in patients with recent HIV-1 infection and T215D/E/F/I/S/Y were the most common RAMs in those with chronic HIV-1 infection. 2013 PloS one Discussion HIV M184I;M184V;T215D;T215D;T215E;T215E;T215F;T215F;T215I;T215I;T215S;T215S;T215Y;T215Y 37;37;85;171;171;85;171;85;171;85;171;85;171;85 44;44;100;186;186;100;186;100;186;100;186;100;186;100 HIV infections;HIV infections 227;151 250;166 23826076 Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients. We also noted higher frequencies of K70R and M46I in patients with recent HIV-1 infection. 2013 PloS one Discussion HIV K70R;M46I 36;45 40;49 HIV infections 74 89 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Alternatively, the lattice of E45A CA cores may be more leaky, allowing small molecules to gain access inside. 2013 Retrovirology Discussion HIV E45A 30 34 Capsid 35 37 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Further high-resolution studies comparing WT and E45A CA cores are needed to determine if they differ in lattice structure or flexibility. 2013 Retrovirology Discussion HIV E45A 49 53 Capsid 54 56 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Furthermore, reverse transcription was initiated more rapidly for E45A HIV-1 as compared to WT HIV-1 or the other mutants tested. 2013 Retrovirology Discussion HIV E45A 66 70 RT 13 34 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. However, the majority of the E45A CA remains intact, delaying completion of reverse transcription as compared to WT HIV-1. 2013 Retrovirology Discussion HIV E45A 29 33 RT;Capsid 76;34 97;36 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Importantly, the second-site suppressor mutation, R132T, partially restored the E45A RNA staining kinetics to wild type, correlating the effect of E45A mutation on RNA accessibility with its impairment of infectivity. 2013 Retrovirology Discussion HIV E45A;E45A;R132T 80;147;50 84;151;55 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. In contrast to the K203A mutant, cytoplasmic E45A cores initially exhibited a small transient increase in RNA staining between 15 and 25 minutes post-infection, similar to WT cores. 2013 Retrovirology Discussion HIV E45A;K203A 45;19 49;24 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. It was surprising that the E45A mutant, which was described as having a more stable capsid than WT HIV-1 , consistently exhibited RNA accessibility kinetics that resembled those of mutants with unstable capsids. 2013 Retrovirology Discussion HIV E45A 27 31 Capsid;Capsid 84;203 90;210 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Our previous results using correlative live-cell microscopy and cryo-electron tomography of infected cells suggested that E45A CA cores disassociate more slowly intracellularly than WT cores . 2013 Retrovirology Discussion HIV E45A 122 126 Capsid 127 129 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. The K203A CA mutant, which has been described as having a more fragile core than WT , showed more rapid loss of vRNA staining. 2013 Retrovirology Discussion HIV K203A 4 9 Capsid 10 12 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. This was followed by a rapid decrease in vRNA staining as observed for the unstable K203A mutant. 2013 Retrovirology Discussion HIV K203A 84 89 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. We suggest that for the E45A mutant virus, the first uncoating step occurs more rapidly than for WT HIV-1 but that the second uncoating step is delayed relative to WT HIV-1. 2013 Retrovirology Discussion HIV E45A 24 28 23835323 Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. While the comparable behavior of the K203A and E45A mutants appears contradictory, it supports the hypothesis that a subtle HIV-1 CA uncoating event precedes and is independent of a more extensive dissociation of CA from the core. 2013 Retrovirology Discussion HIV E45A;K203A 47;37 51;42 Capsid;Capsid 130;213 132;215 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. F312W/T314A/E317D and one other mutation are required to acquire noncompetitive resistance. 2013 PloS one Discussion HIV E317D;T314A;F312W 12;6;0 17;11;5 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. HIV-1234 could not be passaged in PM1/CCR5 cells in the presence of 1 microM maraviroc because of its poor viral fitness (data not shown), suggesting that F312W/T314A/E317D is a type of fitness "valley" that needs to be selected on the genetic pathway for the development of noncompetitive resistance. 2013 PloS one Discussion HIV E317D;F312W;T314A 167;155;161 172;160;166 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. In addition, we showed that in combination with the V3 mutations, a T199K mutation in the C2 region enhanced viral fitness (Figures 4, 5). 2013 PloS one Discussion HIV T199K 68 73 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. In the HIV-1JR-FLan background, F312W/T314A/E317D is a crucial combination for maraviroc resistance, and I318V was required for extensive replication comparable with that in the wild type (Figure 5). 2013 PloS one Discussion HIV E317D;F312W;T314A;I318V 44;32;38;105 49;37;43;110 23840315 Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. We could not select a maraviroc-resistant virus from the homogeneous viral population of HIV-1JR-FLan because spontaneous multiple mutations ( 4) were unlikely to occur during in vitro passages, whereas our V3 virus library inherently contained F312W/T314A/E317D and fitness-enhancing mutations (I304V/I318V). 2013 PloS one Discussion HIV E317D;F312W;T314A;I304V;I318V 257;245;251;296;302 262;250;256;301;307 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Among patients with virological failure on a first-line dual NRTI plus NNRTI regimen, a higher proportion of those who received TDF and/or ABC had the non-TAMs K65R, K70EQG, L74VI, and Y115F compared with those receiving d4T or AZT. 2013 PloS one Discussion HIV K65R;K70E;K70G;K70Q;L74I;L74V;Y115F 160;166;166;166;174;174;185 164;172;172;172;179;179;190 NNRTI;NRTI 71;61 76;65 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. As in our study, M184V, K65R, and Y115F were the most common major NRTI mutations. 2013 PloS one Discussion HIV K65R;M184V;Y115F 24;17;34 28;22;39 NRTI 67 71 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. Indeed, the risk of K65R was significantly higher in the 20 patients receiving TDF plus 3TC plus NVP compared to the 133 patients receiving TDF plus 3TC plus EFV, a finding consistent with previous reports questioning the efficacy of TDF plus 3TC plus NVP. 2013 PloS one Discussion HIV K65R 20 24 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. M184V, the most common NRTI-resistance mutation, occurred in a significantly but only modestly higher proportion of patients receiving an AZT- or d4T-containing regimen compared with those receiving a TDF- or ABC-containing regimen. 2013 PloS one Discussion HIV M184V 0 5 NRTI 23 27 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. The distribution of NNRTI resistance mutations was consistent with previous studies: V106M was significantly more common among patients receiving EFV and Y181C was significantly more common among patients receiving NVP. 2013 PloS one Discussion HIV V106M;Y181C 85;154 90;159 NNRTI 20 25 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. The former association is surprising because Y181C increases TDF susceptibility. 2013 PloS one Discussion HIV Y181C 45 50 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. The presence of L74V in patients who failed TDF-based regimen was also surprising as L74V increased TDF susceptibility in vitro . 2013 PloS one Discussion HIV L74V;L74V 16;85 20;89 23840622 Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. The statistical associations of Y181C with TDF and of L100I with ABC have not previously been reported. 2013 PloS one Discussion HIV L100I;Y181C 54;32 59;37 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. In all four resistance induction experiments the rare N276D point mutation emerged. 2013 PloS one Discussion HIV N276D 54 59 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Moreover, the D368R mutation in the heart of the CD4bs, well known to abrogate binding of b12, didn't affect HJ16 binding to gp120. 2013 PloS one Discussion HIV D368R 14 19 gp120 125 130 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Of these N332S and N386T also abrogated the neutralizing capacity of mAb 2G12, as could be expected. 2013 PloS one Discussion HIV N332S;N386T 9;19 14;24 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Our data on increased sensitivity of N276D mutants of subtype A, C and CRF02 Env towards neutralization by VRC01 therefore provide an important functional correlate to McGuire's and Jardine's observations and indicate that the interactions between the N276 glycan and the VRC01 light chain residues is in fact not a requirement for antibody binding. 2013 PloS one Discussion HIV N276D 37 42 Env 77 80 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. Remarkably the N276S mutation also increased sensitivity to neutralization by two patient sera. 2013 PloS one Discussion HIV N276S 15 20 23874792 The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. We applied site directed mutagenesis in the VI1090 CFR02_AG env to confirm that this mutation was responsible for the resistance to HJ16 in VI1090 and showed in addition that introducing the N276D mutation in sensitive A and C isolates also induced full resistance to HJ16. 2013 PloS one Discussion HIV N276D 191 196 Env 60 63 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. In the case of the protease mutations, a statistically significant difference for L90M has been noticed since 2003 and the statistically significant difference observed for M46I in 2003 reappeared in 2005. 2010 Boletin de la Asociacion Medica de Puerto Rico Discussion HIV L90M;M46I 82;173 86;177 PR 19 27 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. K103N was the only statistically significant mutation in the RT gene obtained in the 2005 data. 2010 Boletin de la Asociacion Medica de Puerto Rico Discussion HIV K103N 0 5 RT 61 63 23875516 Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005. The K103N RT mutation was more common in women while the protease mutations L90M and M46I were more prevalent in men. 2010 Boletin de la Asociacion Medica de Puerto Rico Discussion HIV K103N;L90M;M46I 4;76;85 9;80;89 PR;RT 57;10 65;12 23904291 Persistence of HIV-1 transmitted drug resistance mutations. In a recent study of patients with acute/early infection all TAMs were combined for analysis, but we found marked variation within this group of mutations, with T215F/Y and K70R being lost more rapidly than other TAMs. 2013 The Journal of infectious diseases Discussion HIV K70R;T215F;T215Y 173;161;161 177;168;168 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Lesser heterogeneity was observed for NNRTI and PI mutations, and mutations from these classes were lost more rapidly than the T215 revertants and the more stable TAMs, such as M41L. 2013 The Journal of infectious diseases Discussion HIV M41L 177 181 NNRTI;PI 38;48 43;50 23904291 Persistence of HIV-1 transmitted drug resistance mutations. M184V was lost rapidly, although at a lower rate than reported by Jain et al, possibly reflecting a selection bias in our analysis. 2013 The Journal of infectious diseases Discussion HIV M184V 0 5 23904291 Persistence of HIV-1 transmitted drug resistance mutations. Only including patients identified during acute infection would minimize this effect, although, even then, some highly unfit mutations such as M184V could still be missed. 2013 The Journal of infectious diseases Discussion HIV M184V 143 148 23904291 Persistence of HIV-1 transmitted drug resistance mutations. They reported that at least 2 mutations (K70R and Y181C) could form self-sustaining transmission chains. 2013 The Journal of infectious diseases Discussion HIV K70R;Y181C 41;50 46;55 23977189 HIV-1 drug-resistance surveillance among treatment-experienced and -naive patients after the implementation of antiretroviral therapy in Ghana. Furthermore, nearly half of the cases (45.2%, 14/31) had both NRTI- and NNRTI-resistance mutations (Table 4), a pattern that is consistent with that observed in a recent systematic review on treatment-failure cases in sub-Saharan Africa, where M184V/I, K103N, and T215Y/F mutations predominate. 2013 PloS one Discussion HIV K103N;M184I;M184V;T215F;T215Y 253;244;244;264;264 258;251;251;271;271 NNRTI;NRTI 72;62 77;66 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Alternatively, when considering Q92R, it may attenuate interaction between the epitope and complementary cytotoxic T-cell receptor. 2013 PloS one Discussion HIV Q92R 32 36 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Although the PR:76-84 HLA-A*02 restricted epitope could not be detected by analytical methods here, the enhanced Y9V epitope produced by RT:M184V was detected by observing higher frequencies of the HLA-A*02 negatively correlated RT mutation, E203D in the presence of RT M184V. 2013 PloS one Discussion HIV E203D;M184V;M184V;Y9V 242;140;270;113 247;145;275;116 PR;RT;RT;RT 13;137;229;267 15;139;231;269 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Compensating for correlated mutations, whose lower frequency may bias the observed frequency of L90M, still yielded significant results. 2013 PloS one Discussion HIV L90M 96 100 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Even though the existence of LM9L and M10F may be proven with subsequent studies, there is no indication here of the immunogenicity of the epitope. 2013 PloS one Discussion HIV M10F 38 42 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. From the results, it is proposed that two novel epitopes LMTQIGCTL, HLA-B*15/B*48 (LM9L) and possibly MTQIGCTLF (M10F, HLA-A*32) are revealed by the PI resistance related mutation L90M and provide a causal relationship to decreased frequencies of L90M. 2013 PloS one Discussion HIV L90M;L90M;M10F 180;247;113 184;251;117 PI 149 151 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. Further evidence are deduced from NetChop results that suggest a highly probable proteasomal cleavage site near the C-terminus of M9L, which is essential, since trimming of proteasomal fragments usually only occur at the N-terminus of the peptide. 2013 PloS one Discussion HIV M9L 130 133 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. It should be emphasized that if either M9L or M10F is shown in subsequent studies to indeed be immunogenic CTL epitopes, it could be prudent to include PIs in treatment regiments such as Saquinavir or Nelfinavir for which L90M is a major resistance mutation. 2013 PloS one Discussion HIV L90M;M10F;M9L 222;46;39 226;50;42 PI 152 155 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The contribution of L90M to viral fitness may also outweigh the immunological pressure induced by L90M. 2013 PloS one Discussion HIV L90M;L90M 20;98 24;102 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The fitness cost of PR Q92K/R is unknown and insufficient data was available here to do a rigorous analysis. 2013 PloS one Discussion HIV Q92K;Q92R 23;23 29;29 PR 20 22 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The L90M mutation does appear to occur at lower frequencies, but the reason for the lack of complete elimination need to be investigated. 2013 PloS one Discussion HIV L90M 4 8 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The marked increase in affinity of the M9L to HLA subtypes B*15 and B*48 as well as a predicted increased affinity of M10F for A*32, provide a possible mechanism of epitope elucidation. 2013 PloS one Discussion HIV M10F;M9L 118;39 122;42 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The predicted creation of a proteasomal cleavage site by Q92K, which is internal to both LM9L and M10F may be an escape mutation. 2013 PloS one Discussion HIV M10F;Q92K 98;57 102;61 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The sequences from patients with the assigned HLA subtypes B*15, B*48 and A*32 demonstrated exclusive lower frequencies of L90M. 2013 PloS one Discussion HIV L90M 123 127 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. The T9F escape mutation, I93L, is predicted with high probability to produce a proteasomal cleavage site. 2013 PloS one Discussion HIV I93L;T9F 25;4 29;7 24015196 Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. This lead to the conclusion that the diminished frequencies of L90M in the presence of HLA B*15 and B*48 are not spurious. 2013 PloS one Discussion HIV L90M 63 67 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Consistently, we have shown that both the IN-negative and the class II IN mutant viruses (L241A or K258A) exhibited a clear block at the early stages of reverse transcription, a phenotype shared by viruses produced in the presence of NCINIs (Figure S2). 2013 PloS one Discussion HIV K258A;L241A 99;90 104;96 RT;IN;IN 153;42;71 174;44;73 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. Importantly, we show here that an HIV-1 variant with the T174I mutation was resistant to the late-stage inhibitory effect of NCINIs. 2013 PloS one Discussion HIV T174I 57 62 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. In addition, the progeny virus harboring a Q168A mutation in IN that disrupts its binding to LEDGF was replication defective due to a block in vDNA integration, but the mutant virions showed no late-stage defects and supported normal reverse transcription in target cells. 2013 PloS one Discussion HIV Q168A 43 48 RT;IN 234;61 255;63 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. In the case of the HIV variant with IN mutation C130S that exhibits a block at the reverse transcription step, biochemical findings suggest a disruption of the direct IN-RT interaction as a potential cause. 2013 PloS one Discussion HIV C130S 48 53 RT;IN;IN;RT 83;36;167;170 104;38;169;172 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. T174I IN was among the resistance mutations selected by GS-A and GS-B and confers high-level resistance to NCINIs. 2013 PloS one Discussion HIV T174I 0 5 IN 6 8 24040198 Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells. that the NCINI resistance-conferring A128T mutation perturbs the ability of NCINIs to bind and promote IN multimerization with minimal impact on IN-LEDGF binding. 2013 PloS one Discussion HIV A128T 37 42 IN;IN 103;145 105;147 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. Nevertheless, the 76.1% prevalence of the L89M protease polymorphism raises concern. 2013 BMC infectious diseases Discussion HIV L89M 42 46 PR 47 55 24053581 HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania. The L89M mutation increases the catalytic efficiency and vitality of the HIV-1 protease gene in the presence of other protease mutations in non-B African viral subtypes and can determine a low accumulation of primary protease mutations in non-B subtypes. 2013 BMC infectious diseases Discussion HIV L89M 4 8 PR;PR;PR 79;118;217 87;126;225 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. At the mutation level, K103N represents around the 50% of NNRTI primary resistance in the last two periods while the remaining 50% was dominated by the V108I mutation in the previous study and by the G190A mutation in the present study. 2013 Journal of the International AIDS Society Discussion HIV G190A;K103N;V108I 200;23;152 205;28;157 NNRTI 58 63 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. Interestingly, we found a high prevalence of G190A, not previously reported in the region; and the absence of V108I, found about equally often as K103N in our previous study during 2003-2005. 2013 Journal of the International AIDS Society Discussion HIV G190A;K103N;V108I 45;146;110 50;151;115 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. It is important to highlight that, as reported by June 2010, in Buenos Aires the 86.6% of patients treated with NNRTIs were under efavirenz-based regimens and the remaining 13.3% were under nevirapine-based regimens, which are significantly impaired by K03N mutation. 2013 Journal of the International AIDS Society Discussion HIV K03N 253 257 NNRTI 112 118 24093951 Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina. Therefore, it is likely that ARV treatment constitute indeed the population-level selective force driving persistence of this mutation in our population since K103N is not a natural polymorphism of the virus circulating in our region. 2013 Journal of the International AIDS Society Discussion HIV K103N 159 164 24119088 Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana. At virologic failure, 67% of the children harbored viruses with >= 1 DRMs, and dual-class resistance was observed in 50% with M84V/K103N being the predominant resistance pathway. 2013 BMC infectious diseases Discussion HIV K103N;M84V 131;126 136;130 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. A comparison of the wild-type and Q148H/G140S IN models suggests that the Q148H mutation alone may displace residues Y143 through G149 from their wild-type positions because of the larger steric bulk of His versus Asn and the plausible redirection of the H-bond trajectory between the side chains of Q148H and H114 assuming the interaction forms. 2013 PloS one Discussion HIV G140S;Q148H;Q148H;Q148H 40;34;74;300 45;39;79;305 IN 46 48 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Along with the predicted structural disturbances that the Q148H/K/R mutations may induce, there exist the inherent associated strain energies. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 58;58;58 67;67;67 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Although not clear from the Q148R/K models, we nonetheless expect the H-bond between the backbone CO of Q148H and backbone NH of E152 to be weakened because of the strain induced by the mutations. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 104;28;28 109;35;35 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Although the Y143H mutation is not associated with a substantial loss in anti-HIV activity, the minor 1.8-fold increase in EC50 is likely associated with the decreased dissociative t1/2 of RAL. 2013 PloS one Discussion HIV Y143H 13 18 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Although this pi-stacking interaction is non-optimal due likely to the N155H mutation, the nucleobase is nonetheless in position to also slow the egress of DTG from the catalytic pocket. 2013 PloS one Discussion HIV N155H 71 76 PI 14 16 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Because of the structural disturbances and associated strain energy arising from the Q148H/G140S mutations, the binding of RAL, EVG and DTG should be negatively impacted; this is clearly supported by their shortened dissociative half-lives relative to wild-type IN (Table S1 in File S1). 2013 PloS one Discussion HIV G140S;Q148H 91;85 96;90 IN 262 264 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Biochemical support for the increased disorder of the active-site loop of Q148H IN lies in the fact that the catalytic activity of the mutant enzyme is severely impaired. 2013 PloS one Discussion HIV Q148H 74 79 IN 80 82 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Dolutegravir maintains prolonged binding with the Y143C/H/R mutants as demonstrated by dissociative t1/2 values of 42 to 60 hours. 2013 PloS one Discussion HIV Y143C;Y143H;Y143R 50;50;50 59;59;59 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Dolutegravir's slow dissociation from the N155H IN-DNA complex has similar underpinnings as described for the Q148H/K/R mutations. 2013 PloS one Discussion HIV N155H;Q148H;Q148K;Q148R 42;110;110;110 47;119;119;119 IN 48 50 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For EVG, the decrease in antiviral activity was >890-fold, which we speculate reflects the structural strain induced by the Q148H/G140S mutations. 2013 PloS one Discussion HIV G140S;Q148H 130;124 135;129 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For EVG, the reduced anti-HIV activity against the Q148H/K/R IN viral strains is consistent with decreased binding to the mutant IN-DNA complexes. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 51;51;51 60;60;60 IN;IN 61;129 63;131 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For EVG, there was insufficient binding to the IN-DNA complex to measure a dissociative t1/2 involving Q148K/R IN. 2013 PloS one Discussion HIV Q148K;Q148R 103;103 110;110 IN;IN 47;111 49;113 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. For Q148H IN, we predict that the mutant residue still undergoes a large positional shift away from the DDE motif, but without disruption of the 310 helix, and consequently still creates strain at the C-terminal end of the active-site loop weakening the H-bond between the backbone CO of Q148H and backbone NH of E152 as in the Q148H/G140S IN model. 2013 PloS one Discussion HIV G140S;Q148H;Q148H;Q148H 334;4;288;328 339;9;293;333 IN;IN 10;340 12;342 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. From this position, the N155H mutation may induce the structural disturbances modeled in the N155H IN-DNA complex (Figure 4B), which include deformation of the alpha4 helix through disruption of backbone H-bonds among the neighboring residues, E152, S153, K156 and E157, and a widening of the catalytic pocket's base between residues D64 and N155H to accommodate the larger steric bulk of His versus Asn. 2013 PloS one Discussion HIV N155H;N155H;N155H 24;93;342 29;98;347 IN 99 101 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. However, greater losses in antiviral potency were observed for the Q148K/R IN viral strains with fold increases in EC50 of >1700 and 240, respectively, versus the 7.3-fold increase against the Q148H IN mutant. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 193;67;67 198;74;74 IN;IN 75;199 77;201 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. However, it is also possible that the N-terminal end of Q148H IN's active-site loop may become more disordered because of the flexibility that residue G140 imparts on the loop, the inability of residue G140 to H-bond with the side chains of Q148H and E138, and the strain energy induced by the mutation itself. 2013 PloS one Discussion HIV Q148H;Q148H 56;241 61;246 IN 62 64 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. However, the losses in potency against the Q148K/R IN viral strains are far greater than expected when one considers the inhibitor's fold increase in EC50 for the Q148H IN mutant against the shortened dissociative t1/2. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 163;43;43 168;50;50 IN;IN 51;169 53;171 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. In contrast to RAL and EVG, the Q148H/K/R IN mutations had no appreciable effect on the in vitro anti-HIV activity of DTG, despite the inhibitor's faster dissociation compared with wild-type IN. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 32;32;32 41;41;41 IN;IN 42;191 44;193 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. N155H HIV-1 Integrase. 2013 PloS one Discussion HIV N155H 0 5 IN 12 21 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Notably, the Y143R mutation had the most negative effect on RAL's antiviral activity consistent with the magnitude of the decrease in its dissociative t1/2, both of which were expected given the size, flexibility and formal charge of Arg. 2013 PloS one Discussion HIV Y143R 13 18 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Note, from Table S1 in File S1, however, that EVG's dissociative t1/2 values with Y143C/H/R, which range from 1.6 to 2.1 hours, are comparable in magnitude to those of RAL, yet EVG has near wild-type antiviral activity. 2013 PloS one Discussion HIV Y143C;Y143H;Y143R 82;82;82 91;91;91 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Q148H/G140S HIV-1 Integrase. 2013 PloS one Discussion HIV G140S;Q148H 6;0 11;5 IN 18 27 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Q148H/G140S is the most common combination of primary and secondary IN mutations within the Q148 resistance pathway, likely due to the almost full restoration of catalytic activity with the addition of G140S to Q148H. 2013 PloS one Discussion HIV G140S;G140S;Q148H;Q148H 6;202;211;0 11;207;216;5 IN 68 70 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Q148H/K/R HIV-1 Integrases. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 0;0;0 9;9;9 IN 16 26 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Raltegravir's antiviral activity was decreased >130-fold, which is >10-fold over that reported for Q148H IN reflecting the further decrease in binding that we attribute to the decrease in flexibility of the active-site loop and the inhibitor occupying the catalytic pocket's full height. 2013 PloS one Discussion HIV Q148H 99 104 IN 105 107 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Residue Q148H undergoes the largest positional shift away from the DDE motif in order to accommodate the larger steric bulk of His versus Gln creating strain in the enzyme and weakening the H-bond between the backbone CO of Q148H and backbone NH of E152. 2013 PloS one Discussion HIV Q148H;Q148H 8;224 13;229 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Similar to Q148H IN, we predict that the Q148K/R mutations also perturb the structure of the active-site loop given the larger steric bulk of Lys and Arg versus Asn and the steric clash with residue P145 that existed prior to structural refinement of the Q148R/K IN models. 2013 PloS one Discussion HIV Q148H;Q148K;Q148K;Q148R;Q148R 11;41;255;41;255 16;48;262;48;262 IN;IN 17;263 19;265 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Support from the N224H PFV intasome structures in 3OYN and 3S3O is not definitive since the positional shifts of the Mg2+ ions (in particular, that coordinated to D128 and E221), and non-hydrogen atoms of the complexing ligands (eg, residues of the DDE motif, DTG) are at or near the boundary of atomic position error. 2013 PloS one Discussion HIV N224H 17 22 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The 4.4-, 3.5- and 8-fold decreases in RAL's dissociative t1/2 caused by the Y143C/H/R mutations (Table S1 in File S1), respectively, provide evidence for the compromised inhibitor binding to the mutant enzymes. 2013 PloS one Discussion HIV Y143C;Y143H;Y143R 77;77;77 86;86;86 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The decreases in RAL's dissociative t1/2 produced by the Q148K/R mutations were >=22-fold to 0.3 and 0.4 hours, respectively, which were greater than those of DTG with decreases of 6.5- to 7.7-fold to 11 and 9.2 hours, respectively. 2013 PloS one Discussion HIV Q148K;Q148R 57;57 64;64 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The lack of a substituent para to DTG's hydroxyl group, we predict, allows the terminal 3' adenine to pi-stack against the inhibitor's scaffold as shown in the N155H IN-DNA-DTG model (Figure 4B). 2013 PloS one Discussion HIV N155H 160 165 IN;PI 166;102 168;104 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The losses in anti-HIV activity for RAL of 13-, 83- and 47-fold against the Q148H/K/R IN viral strains, respectively, likely reflect the decreases in binding to the mutant IN-DNA complexes. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 76;76;76 85;85;85 IN;IN 86;172 88;174 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The N155H mutation had a greater negative effect on RAL's dissociative t1/2 compared with those of EVG and DTG. 2013 PloS one Discussion HIV N155H 4 9 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Q148H mutation reduced the dissociative t1/2 of RAL by 44-fold to 0.2 hours, whereas those of DTG and EVG were reduced roughly 13.5-fold to 5.2 and 0.2 hours, respectively. 2013 PloS one Discussion HIV Q148H 4 9 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Q148H/G140S IN-DNA model (Figure 4A) shows, however, that the amino acid substitutions do affect the structure of the active-site loop displacing most of its residues from their wild-type positions; the side chains of H114 and E138 are also displaced to accommodate the G140S mutation and form some of the H-bonds in the specified network. 2013 PloS one Discussion HIV G140S;G140S;Q148H 10;274;4 15;279;9 IN 16 18 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. The Y143C/R mutations confer significant resistance to RAL as supported by the 3.2- and 16-fold increases in EC50, respectively, and we speculate that these results are likely in part due to RAL's faster off-rates from these IN mutants. 2013 PloS one Discussion HIV Y143C;Y143R 4;4 11;11 IN 225 227 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. This hypothesis may help to explain why insufficient signal was generated for EVG with the IN-DNA complexes containing Q148K/R substitutions in the dissociation studies. 2013 PloS one Discussion HIV Q148K;Q148R 119;119 126;126 IN 91 93 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. To account for this, we speculate that the predicted displacement of residue P145 by the Q148K/R mutations may negatively affect RAL's on-rate as the side chain of P145 may lie in position to sterically hinder the inhibitor's approach through its gem-dimethyl group. 2013 PloS one Discussion HIV Q148K;Q148R 89;89 96;96 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. We attribute this to the formation of an H-bond network between residues H114, E138, G140S and Q148H, which may help stabilize the active-site loop into a near wild-type, catalytically active conformational state decreasing the disorder of the loop introduced by the primary mutation. 2013 PloS one Discussion HIV G140S;Q148H 85;95 90;100 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. We predict that this pi-stacking interaction will not be appreciably affected by the Q148H/K/R mutations given the residue's position within the catalytic pocket. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 85;85;85 94;94;94 PI 21 23 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. We propose based on the predicted rotameric state of Arg in Q148R IN (Figure 3) and Lys in Q148K IN (not shown) that EVG's carboxylate will preferentially form an ionic interaction with the positively charged side chains of these residues, consequently impeding EVG from chelating the metal cations at the catalytic site. 2013 PloS one Discussion HIV Q148K;Q148R 91;60 96;65 IN;IN 66;97 68;99 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Where comparisons are possible, note the greater negative impact of the Q148H/K/R IN mutations on RAL's binding compared with DTG and EVG. 2013 PloS one Discussion HIV Q148H;Q148K;Q148R 72;72;72 81;81;81 IN 82 84 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. While we recognize that the structural disturbances induced by the Q148H/G140S mutations are not solely attributable to residue Q148H, it is possible that these changes are simply not as pronounced in Q148H IN given that it merely has to accommodate the "hydrogen" side chain of G140, whereas Q148H/G140S IN has the hydroxymethyl side chain of G140S. 2013 PloS one Discussion HIV G140S;G140S;G140S;Q148H;Q148H;Q148H;Q148H 73;299;344;67;128;201;293 78;304;349;72;133;206;298 IN;IN 207;305 209;307 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. With residue G140 at the N-terminal end of the active-site loop, the expectation again is that the loop becomes more disordered as supported biochemically by the severely impaired catalytic activities of the Q148K/R IN mutants. 2013 PloS one Discussion HIV Q148K;Q148R 208;208 215;215 IN 216 218 24146996 Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. Y143C/H/R HIV-1 Integrases. 2013 PloS one Discussion HIV Y143C;Y143H;Y143R 0;0;0 9;9;9 IN 16 26 24147057 Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. For example, 48% to 64% of new NNRTI mutations consisted of the amino acid change K103N (data not shown), which is known to emerge rapidly and to confer full resistance to EFV and NVP. 2013 PloS one Discussion HIV K103N 82 87 NNRTI 31 36 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Although both C12C and C1-28 were dually specific to both wild type and early mutant, the character of early mutation and their TCR/pMHC structure were quite different. 2013 Scientific reports Discussion HIV C12C 14 18 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Although H27-14 TCR kept moderate affinity against F139L (KD = 64.8 +- 3.4), its TCR pocket was a better fit for bulky side chain of F139(P6-F) than for small side chain of 139L(P6-L). 2013 Scientific reports Discussion HIV F139L 51 56 Gag;Gag 138;178 140;180 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Although the number of patients are still limited, late mutation in Nef134-10 epitope, F139L, occurred only in the patients without early/ultimate Y135F mutation. 2013 Scientific reports Discussion HIV F139L;Y135F 87;147 92;152 Nef 68 71 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Although Y135F mutation interrupted this hydrogen bond, T138(P5-T) acted like a subanchor forming a hydrogen bond with HLA-A24 His70 keeping the M conformation very similar to the wild type. 2013 Scientific reports Discussion HIV Y135F 9 14 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Clone C12C was cross-reactive to both wild type and early appearing Leu268Met mutant. 2013 Scientific reports Discussion HIV C12C;L268M 6;68 10;77 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. F139L mutation did not cause gross conformational change in the epitope, however, the solvent accessible surface area of the side chain became substantially smaller by the mutation. 2013 Scientific reports Discussion HIV F139L 0 5 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. F139L was a minor but also HLA-A24-related mutation. 2013 Scientific reports Discussion HIV F139L 0 5 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Hence, Y135F is the ultimate escape mutation which appears early in the clinical course. 2013 Scientific reports Discussion HIV Y135F 7 12 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. HIV-1 with Y135F mutation has been accumulating in the population with high HLA-A24 prevalence such as Japanese. 2013 Scientific reports Discussion HIV Y135F 11 16 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. In the case of KK10 epitope restricted by HLA-B*2705, Leu268Met was an early mutation affecting TCR recognition and the ultimate mutations such as Arg264Lys disrupting antigen presentation follow later. 2013 Scientific reports Discussion HIV L268M;R264K 54;147 63;156 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. In the great majority of HLA-A24-positive chronically infected patients, plasma viruses had Y135F mutation, while the patients harbored dual specific CD8+ T cell population with highly restricted TCR repertoire. 2013 Scientific reports Discussion HIV Y135F 92 97 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. In the population with high HLA-A24 prevalence, HIV-1 with the wild type Nef134-10 epitope is replaced by the virus with Y135F mutation early after infection. 2013 Scientific reports Discussion HIV Y135F 121 126 Nef 73 76 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Intriguingly, all 6 patients with F139L mutation kept the wild type residue at 135th position in the epitope. 2013 Scientific reports Discussion HIV F139L 34 39 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. It is tempting to speculate that the Y135F mutation could be an example of "stealth mutation." HIV-1-infected cells might not be detected by specific- or dual-specific CTL due to processing failure or excess processing. 2013 Scientific reports Discussion HIV Y135F 37 42 HIV infections 95 109 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Namely, the epitope became slightly featureless by F139L mutation. 2013 Scientific reports Discussion HIV F139L 51 56 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Or HIV-1 with Y135F may infect HLA-A24-positive people. 2013 Scientific reports Discussion HIV Y135F 14 19 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Our previous study suggesting that Y135F was a processing mutation was later confirmed by others. 2013 Scientific reports Discussion HIV Y135F 35 40 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. The binding affinity against early/major Y135F mutation diminished to nonfunctional level (KD = 291.5 +- 63.8). 2013 Scientific reports Discussion HIV Y135F 41 46 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. These findings may suggest that CTL with H27-14 TCR clonotype could contribute to eliminate HIV-1 with the wild type epitope but might be responsible for selection of viruses with the late/minor F139L mutation in vivo. 2013 Scientific reports Discussion HIV F139L 195 200 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Whichever the case, HIV-1 with Y135F mutation replicate for many years in the presence of activated dual-specific CTL. 2013 Scientific reports Discussion HIV Y135F 31 36 24192765 Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Y135F was the major escape mutation which appeared early in the clinical course. 2013 Scientific reports Discussion HIV Y135F 0 5 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. In the same study M184V/I occurred in 84%, K65R in 11%, and Q151M in 5% with TAMs occurring in 18% of the NRTIs resistance mutations. 2013 AIDS research and therapy Discussion HIV K65R;M184I;M184V;Q151M 43;18;18;60 47;25;25;65 NRTI 106 111 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. In the Thai children, Y181C occurred in 58% and K103N in 34% of NNRTIs RAMs. 2013 AIDS research and therapy Discussion HIV K103N;Y181C 48;22 53;27 NNRTI 64 70 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. M184V has been shown to emerge in high prevalence among children and adults failing on a 3TC-containing regimen in developed countries. 2013 AIDS research and therapy Discussion HIV M184V 0 5 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. Resistance profiles that were performed prior to switching to second line, revealed the M184V and the K103N being the commonly observed NRTI and NNRTI RAMs, respectively. 2013 AIDS research and therapy Discussion HIV K103N;M184V 102;88 107;93 NNRTI;NRTI 145;136 150;140 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. The current study reports more of the K103N as opposed to the Y181C in the NNRTIs while the proportion of M184V was consistent with the previous study. 2013 AIDS research and therapy Discussion HIV K103N;M184V;Y181C 38;106;62 43;111;67 NNRTI 75 81 24215971 Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. This finding was expected as most of the children at JCRC (current study) were on an efavirenz containing regimen that induces commonly the K103N as opposed to nevirapine that induces commonly the Y181C which occurred in the Thai study. 2013 AIDS research and therapy Discussion HIV K103N;Y181C 140;197 145;202 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. A327P is located at the stem of V3 loop, which has been shown to play a critical role in HIV-1 coreceptor binding. 2013 Retrovirology Discussion HIV A327P 0 5 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. An NL4-3 derivative encoding the V120Q/A327P double mutant showed substantial resistance to NYAD-36, -66 and -67 compared to the WT NL4-3 virus. 2013 Retrovirology Discussion HIV A327P;V120Q 39;33 44;38 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. HSQC NMR experiments confirmed tight binding of these peptides to mutant CA (W184A/M185A). 2013 Retrovirology Discussion HIV M185A;W184A 83;77 88;82 Capsid 73 75 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. reported that an A327G mutation had very little effect on CCR5 binding but it substantially reduced HIV-1 infectivity. 2013 Retrovirology Discussion HIV A327G 17 22 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. Unexpectedly, no mutation associated with resistance was identified in the CA region; rather, resistance mutations mapped to two residues in gp120: V120Q in the C1 region and A327P at the base of the V3 loop. 2013 Retrovirology Discussion HIV A327P;V120Q 175;148 180;153 gp120;Capsid 141;75 146;77 24237936 Dual-acting stapled peptides target both HIV-1 entry and assembly. We speculate that the A327P mutation arose in response to direct binding of the negatively charged stapled peptides, NYAD-36, -66 and -67, to the highly positively charged RKSIRIQRGPGR (in NL4-3 virus) motif around the crown of the V3 loop. 2013 Retrovirology Discussion HIV A327P 22 27 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. As Alix associates with both cortactin and Gag through the V domain, it is possible that the enhanced Gag-Alix binding resulting from the S40F mutation promotes formation of the filopodia-like structures in regions of the membrane where L domain-2-mediates VLP formation. 2013 Retrovirology Discussion HIV S40F 138 142 Gag;Gag 43;102 46;105 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Both S40F and S40A exhibited increased interaction with Alix in the yeast 2-hybrid assay and induced the formation of filopodia-like membrane extensions when transfected into mammalian cells. 2013 Retrovirology Discussion HIV S40A;S40F 14;5 18;9 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. Our study identifies a conserved residue in Gag p6 whose mutation had broad impact on budding: The S40F (and S40A, not shown) mutations (i) interfered with complete separation of particles from the plasma membrane in Tsg101-mediated budding; (ii) exacerbated the block to membrane scission in Alix-mediated budding; and (iii) inhibited bud release in Nedd4-facilitated egress. 2013 Retrovirology Discussion HIV S40A;S40F 109;99 113;103 Gag;Gag 44;48 47;50 24257210 The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities. We provided evidence to support this hypothesis by demonstrating that disrupting Alix interaction with the S40F mutant restored spherical particle formation while suppressing filopodia production. 2013 Retrovirology Discussion HIV S40F 107 111 24268781 Link between primate lentiviral coreceptor usage and Nef function. Approximately half of the viral sequences (14/31) amplified from the viral inoculum contained the I123L and L146M substitutions in Nef that disrupt this function. 2013 Cell reports Discussion HIV I123L;L146M 98;108 103;113 Nef 131 134 24268781 Link between primate lentiviral coreceptor usage and Nef function. In fact, the only other mutation (I132T) known to selectively disrupt the interaction of Nef with the CD3zeta chain was identified in a variant of HIV-2. 2013 Cell reports Discussion HIV I132T 34 39 Nef 89 92 24268781 Link between primate lentiviral coreceptor usage and Nef function. In one animal studied in detail, this loss of function was due to two amino acid substitutions of I123L and L148F in the core region of Nef that specifically disrupted its interaction with the TCR-CD3-zeta chain. 2013 Cell reports Discussion HIV I123L;L148F 98;108 103;113 Nef 136 139 24268781 Link between primate lentiviral coreceptor usage and Nef function. Interestingly, a change at the same position (I132V) preceded the emergence of the I123L and L146F substitutions in SM2 and also became predominant in SM1 later during infection (Figure S3). 2013 Cell reports Discussion HIV I123L;I132V;L146F 83;46;93 88;51;98 24268781 Link between primate lentiviral coreceptor usage and Nef function. The I132V change reduced the effect of Nef on CD3 but did not disrupt it entirely (Figure 5A). 2013 Cell reports Discussion HIV I132V 4 9 Nef 39 42 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. As such, maintenance of the M184V mutation is considered to be clinically useful to sustain this replication disadvantage even in the presence primary drug resistance. 2014 AIDS (London, England) Discussion HIV M184V 28 33 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. Our data suggest that RV could be used as an adjuvant in the treatment of HIV-1, helping to control replication of drug-resistant M184V mutants. 2014 AIDS (London, England) Discussion HIV M184V 130 135 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. RV inhibited viruses carrying M184V, singly or in combination with other mutations. 2014 AIDS (London, England) Discussion HIV M184V 30 35 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. Together, adjuvant treatment with RV, or with more bioavailable derivatives, may increase antiretroviral treatment success in patients by helping control replication of highly prevalent FTC-resistant M184V HIV-1 mutants. 2014 AIDS (London, England) Discussion HIV M184V 200 205 24326355 Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1. We now demonstrate that treatment with RV alone is sufficient to inhibit HIV-1 mutants with the M184V mutation, present in > 50 % of treated patients. 2014 AIDS (London, England) Discussion HIV M184V 96 101 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Additionally, two other mutations (V159I and T280V) were observed specifically in viral variants from HLA-B*57/58:01 positive individuals; however, these mutations could not be related to escape from CTL pressure restricted by HLA-B*57/58:01. 2013 PloS one Discussion HIV T280V;V159I 45;35 50;41 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. An increase in replication kinetics was observed after introduction of two single mutations (L215T and H219Q) in the NL4-3.Ba-L virus containing the HLA-B*57/58:01-specific mutations. 2013 PloS one Discussion HIV H219Q;L215T 103;93 108;99 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Introduction of a combination of mutations L215T and H219Q did not result in a significant increase in replication kinetics compared to the NL4-3.Ba-L virus containing the HLA-B*57/58:01-specific mutations, indicating that the combination of these two mutations does not account for the increase in replication kinetics observed for the virus containing the HLA-B*57/58:01-specific mutations. 2013 PloS one Discussion HIV H219Q;L215T 53;43 58;48 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. Introduction of single mutations H219Q and L215T showed a significant increase in replication capacity, which may suggest that these mutations play a more prominent role in restoration of viral fitness. 2013 PloS one Discussion HIV H219Q;L215T 33;43 38;48 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. reported a higher frequency of mutations H219Q, I223V, M228I, G248A and N252H in combination with the HLA-B*57 T242N CTL escape mutation in sequences obtained from HLA-B*57 progressors than seen in sequences from HLA-B*57 non-progressors. 2013 PloS one Discussion HIV G248A;H219Q;I223V;M228I;N252H 62;41;48;55;72 67;46;53;60;77 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. The compensatory mutations, in particular H219Q, influence viral sensitivity to TRIM5alpha and reduce binding of capsid to CypA. 2013 PloS one Discussion HIV H219Q 42 47 Capsid 113 119 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. To our knowledge, the S126N and L215T mutations have not been associated with an increase in viral fitness in HLA-B*57/58:01 CTL escape variants before, and we are the first to show that these mutations serve as compensatory mutations. 2013 PloS one Discussion HIV L215T;S126N 32;22 37;27 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. We observed that virus isolates from HLA-B*57/58:01 individuals, irrespective of their disease course, contained CTL escape mutations in the TW10 epitope (T242N and G248A) and the IW9 epitope (I147L), and a mutation adjacent to the KF11 epitope (S173T). 2013 PloS one Discussion HIV G248A;I147L;S173T;T242N 165;193;246;155 170;198;251;161 24339913 HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. When comparing viral Gag sequences obtained late in infection from HLA-B*57/58:01 progressors and HLA-B*57/58:01 LTNPs, frequent changes in the amino acid sequence were observed for progressors at 5 positions: S126N, L215T, H219Q, M228I, N252H. 2013 PloS one Discussion HIV H219Q;L215T;M228I;N252H;S126N 224;217;231;238;210 229;222;236;243;215 Gag 21 24 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. A few cases possessing the M46I mutation by bulk sequencing demonstrated a strongly supported identity which was not biased by including the resistance mutations in the analysis. 2013 PloS one Discussion HIV M46I 27 31 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. A previous study demonstrated no impact on therapy responses in patients who had minority-level K65R and M184V mutations when provided regimens that included protease inhibitors; however; because of the small number of patients representing different treatment regimens in that study, the bearing of these mutations could not be fully evaluated. 2013 PloS one Discussion HIV K65R;M184V 96;105 100;110 PR 158 166 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. As major mutations K65R and M184V reduce the clinical efficacy of TDF and 3TC/FTC, respectively, however their clinical impact as minority mutations is not fully clear. 2013 PloS one Discussion HIV K65R;M184V 19;28 23;33 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. For instance, the M46I, the K70R, the 215 intermediate mutations have a lesser impact on fitness than L90M, K65R, and M184V, and, thus, such mutations are likely to persist longer in vivo. 2013 PloS one Discussion HIV K65R;K70R;L90M;M184V;M46I 108;28;102;118;18 112;32;106;123;22 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. For the ten codons associated with resistance (RTI mutations: M41L, K65R, K70R, K103N, Y181C, M184V and T215F/Y, PI mutations: M46I/L and L90M) the prevalence of detectable drug resistance mutations increased from 15.4% to 26.8% using the highly sensitive assays. 2013 PloS one Discussion HIV K103N;K65R;K70R;L90M;M184V;M41L;M46I;M46L;T215F;T215Y;Y181C 80;68;74;138;94;62;127;127;104;104;87 85;72;78;142;99;66;133;133;111;111;92 RT;PI 47;113 50;115 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Genetic linkage analysis provided more insights into the composition of the viral population by showing that L90M, M46I and M46L in many patients existed on separate viral genomes. 2013 PloS one Discussion HIV L90M;M46I;M46L 109;115;124 113;119;128 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. However, with regard to minority M46I variants, we found they did not cluster closely with viruses from persons with majority-level M46I. 2013 PloS one Discussion HIV M46I;M46I 33;132 37;136 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Instead, we note that the NRTI K65R and M184V mutations were both detected as minority populations. 2013 PloS one Discussion HIV K65R;M184V 31;40 35;45 NRTI 26 30 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Moreover, accumulation of compensatory mutations such as L63P and A71V in protease have been demonstrated to increase or restore replicative fitness of PI resistant variants, and that once compensation has taken place reversion to wildtype is prohibited by a less fit intermediate. 2013 PloS one Discussion HIV A71V;L63P 66;57 70;61 PR;PI 74;152 82;154 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. Phylogenetic analysis showed the sequences of minority M46I/L and L90M-positive amplicons were closely related to their source bulk sequences, supporting that the minority sequences detected were unique to the respective patients and were not the result of contamination. 2013 PloS one Discussion HIV L90M;M46I;M46L 66;55;55 70;61;61 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. This may explain, for example, the high prevalence of M46I we detected in this study as bulk and minority species. 2013 PloS one Discussion HIV M46I 54 58 24358257 Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan. This suggested that at least two pairs with majority-level M46I were phylogenetically related whereas those with minority M46I were scattered among the transmitted virus population, unrelated to any of the other cases in our analysis. 2013 PloS one Discussion HIV M46I;M46I 59;122 63;126 24418540 Defining HIV-1 Vif residues that interact with CBFbeta by site-directed mutagenesis. Our results suggest that W89A mutant does not bind to CBFbeta, however this mutant is capable of degradation of A3F and A3G, and supporting replication of the virus in nonpermissive CEM cells. 2014 Virology Discussion HIV W89A 25 29 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. H108A) residues are altered to alanine using both circular dichroism spectroscopy and size-exclusion chromatography. 2014 Retrovirology Discussion HIV H108A 0 5 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. In addition, substitution of histidine for tyrosine at position 30 in Vif was found to correlate with a reduced ability to transmit the virus from mother to child, supporting the importance of this residue for Vif function. 2014 Retrovirology Discussion HIV Y30H 29 66 Vif;Vif 70;210 73;213 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. In addition, Vif H108A bound to Cul5 with reduced binding affinity when compared to wild-type; however, the affinity was stronger than the Vif V25A mutant. 2014 Retrovirology Discussion HIV H108A;V25A 17;143 22;147 Vif;Vif 13;139 16;142 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Isothermal titration calorimetry analyses revealed that both Vif V25A and H27A mutants had a reduced affinity for Cul5 (>90-fold reduction) compared to wild-type Vif, while C-terminal mutant H108A reduced the affinity 6-fold. 2014 Retrovirology Discussion HIV H108A;H27A;V25A 191;74;65 196;78;69 Vif;Vif 61;162 64;165 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. It has not been ruled out whether His28 may play a role in mediating the interaction and suppression of other APOBEC3 proteins; however, previous reports have observed that Vif H28A mutant HIV clones grow as well as wild-type in the presence of A3G or A3F. 2014 Retrovirology Discussion HIV H28A 177 181 Vif 173 176 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. It is plausible that the V25A mutant complex fell apart during the ITC measurement; however, it appeared intact similar to wild-type throughout the purification protocol (Figure 5C). 2014 Retrovirology Discussion HIV V25A 25 29 24422669 HIV-1 Vif N-terminal motif is required for recruitment of Cul5 to suppress APOBEC3. Next, while Vif L24A had a diminished ability to suppress both A3G and A3F, this mutant could still bind to Cul5 as well as CBF-beta and Elo B/C. 2014 Retrovirology Discussion HIV L24A 16 20 Vif 12 15 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Although innocuous for RAL and DTG, the presence of M50I may slightly decrease HIV-1 susceptibility to EVG. 2014 Retrovirology Discussion HIV M50I 52 56 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Although the combination of M50I/R263K did not restore enzyme efficiency (Figure 3D), the M50I polymorphism partially restored integrase maximal activity to 92% of the WT Vmax for M50I/R263K (Figure 3B), as compared to approximately 20% for H51Y/R263K . 2014 Retrovirology Discussion HIV H51Y;M50I;M50I;M50I;R263K;R263K;R263K 243;28;91;181;33;186;248 247;32;95;185;38;191;253 IN 128 137 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Besides its effect on susceptibility to EVG, the biochemical characterization of the M50I integrase enzyme demonstrates that this polymorphism alone does not affect strand-transfer activity. 2014 Retrovirology Discussion HIV M50I 85 89 IN 90 99 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Comparable to H51Y, the addition of M50I to R263K increased resistance against DTG (15.6-fold for M50I/R263K versus 16.5-fold for H51Y/R263K). 2014 Retrovirology Discussion HIV H51Y;H51Y;M50I;M50I;R263K;R263K;R263K 14;130;36;98;44;103;135 18;134;40;102;49;108;140 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Furthermore, both of the H51Y and M50I mutations were innocuous when tested in the absence of R263K. 2014 Retrovirology Discussion HIV H51Y;M50I;R263K 25;34;94 29;38;99 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Here, we provide evidence that M50I alone does not negatively impact integrase strand-transfer activity and HIV replication capacity, an observation that explains the existence of this polymorphic substitution in untreated patients. 2014 Retrovirology Discussion HIV M50I 31 35 IN 69 78 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In addition to M50I, other secondary mutations have emerged in the presence of R263K in tissue culture experiments with DTG. 2014 Retrovirology Discussion HIV M50I;R263K 15;79 19;84 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In agreement with these results, the addition of M50I to R263K did not restore viral infectivity and replication capacity, similar to what has been reported for H51Y/R263K . 2014 Retrovirology Discussion HIV H51Y;M50I;R263K;R263K 161;49;57;166 165;53;62;171 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In contrast, the addition of H51Y to R263K was very detrimental to integrase strand-transfer activity . 2014 Retrovirology Discussion HIV H51Y;R263K 29;37 33;42 IN 67 76 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. In particular, it should be investigated whether M50I is over-represented in patients who have failed EVG-based therapy in clinical trials . 2014 Retrovirology Discussion HIV M50I 49 53 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. M50I is an accessory mutation that was selected in tissue culture subsequent to the emergence of R263K under DTG pressure . 2014 Retrovirology Discussion HIV R263K;M50I 97;0 102;4 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Overall, M50I by itself is unlikely to lead to treatment failure. 2014 Retrovirology Discussion HIV M50I 9 13 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Primary mutations, such as R263K, can often negatively impact integrase enzymatic activity and lower viral replication capacity . 2014 Retrovirology Discussion HIV R263K 27 32 IN 62 71 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. Since the M50I/R263K double mutant decreased integrase affinity for DNA compared to R263K alone (Figure 3C), an effect also observed with H51Y , this combination of mutations did not restore integration. 2014 Retrovirology Discussion HIV H51Y;M50I;R263K;R263K 139;10;15;84 143;14;20;89 IN 45 54 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. This strongly suggests that M50I is unable to compensate for the R263K defect in DNA binding that has been previously reported . 2014 Retrovirology Discussion HIV M50I;R263K 28;65 32;70 24433497 The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness. When associated with the R263K mutation, M50I demonstrates a tendency toward improving maximal strand-transfer activity while decreasing integrase affinity for target DNA, as measured by Vmax and Km values, respectively (Figure 3). 2014 Retrovirology Discussion HIV M50I;R263K 41;25 45;30 IN 137 146 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. The proportion that had complex NRTI resistance patterns, such as three or more TAMs or Q151M complex, was lower (5.5%) than another recent study of 38 children on ART from the same province where 39% had three or more TAMs despite a shorter duration (median = 2.8 yrs; IQR = 1.9- 2.3 yrs) on ART compared with our cohort (median = 3.3 yrs; IQR = 2.5-4.4 yrs). 2014 AIDS research and therapy Discussion HIV Q151M 88 93 NRTI 32 36 24444369 Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort. Whilst in most cases the mutations would be unlikely to significantly compromise a second-line regimen based on a ritonavir-boosted PI, five patients had complex mutation patterns (three or more TAMs or Q151M complex) that might substantially limit the future activity of the NRTI class of drugs. 2014 AIDS research and therapy Discussion HIV Q151M 203 208 NRTI;PI 276;132 280;134 24456757 HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. The most prevalent mutations observed confer high-level resistance to NRTIs (specifically lamivudine, in the case of the M184V mutation) and NNRTIs (specifically nevirapine and efavirenz, in the case of the K103N/S mutation and the Y181C/Y/I/V mutation). 2014 AIDS research and therapy Discussion HIV K103N;K103S;M184V;Y181C;Y181I;Y181V;Y181Y 207;207;121;232;232;232;232 214;214;126;243;243;243;243 NNRTI;NRTI 141;70 147;75 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. A92E sensitivity to CsA is highly variable in different cells. 2014 Retrovirology Discussion HIV A92E 0 4 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. CypA depletion or mutation on CA preventing CypA binding (G89V) prevent HIV-1 restriction mediated by MX2. 2014 Retrovirology Discussion HIV G89V 58 62 Capsid 30 32 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Disruption of CypA-CA interaction with competitive inhibitors or mutation of viral CA restores the infectivity of WT and A92E mutant viruses. 2014 Retrovirology Discussion HIV A92E 121 125 Capsid;Capsid 19;83 21;85 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Here the replication of A92E in the presence of CsA was assessed in 8 cell lines that had previously been characterized and in 19 additional cell lines. 2014 Retrovirology Discussion HIV A92E 24 28 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. HIV-1 carrying either A92E or G94D CA mutations were selected by serial passage of HIV-1 on CD4+-HeLa cells in the presence of CsA. 2014 Retrovirology Discussion HIV A92E;G94D 22;30 26;34 Capsid 35 37 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. In contrast, A92E reverse transcription was decreased when the CypA-CA interaction was disrupted in 293 T, HOS, CEM, TE671 and Jurkat T cells, but this block was rescued at the level of nuclear entry. 2014 Retrovirology Discussion HIV A92E 13 17 RT;Capsid 18;68 39;70 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. It is also interesting to note how different A92E behaves in the presence of CsA when replicating in very similar cell lines such as the Burkitt lymphoma B-cell lines AKATA and BL41, or in the T-cell lines H9 and MT4. 2014 Retrovirology Discussion HIV A92E 45 49 Burkitt lymphoma 137 153 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Moreover, the A92E CA mutation renders HIV-1 more sensitive to this putative restriction factor. 2014 Retrovirology Discussion HIV A92E 14 18 Capsid 19 21 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. MT4 was the only cell line analyzed in which A92E was sensitive to the block in reverse transcription in presence of CsA, but totally independent of the drug at a subsequent step in the replication cycle. 2014 Retrovirology Discussion HIV A92E 45 49 RT 80 101 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. previously analyzed heterokaryons formed by fusing CsA-dependent HeLa cells and CsA-independent 293 T cells, and showed that the CsA-dependence of the A92E and G94D mutants was dominant, suggesting the presence of a cellular restriction factor. 2014 Retrovirology Discussion HIV A92E;G94D 151;160 155;164 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Recently, CA mutant A105T was described for its ability to prevent restriction of HIV-1 replication by a truncated form of the human protein CPSF6. 2014 Retrovirology Discussion HIV A105T 20 25 Capsid 10 12 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Replication of A92E virus was previously described to be dependent on CsA in HeLa and H9 cells, and independent from CsA in MT4, CEM, 293 T, HOS, TE671 and Jurkat T cells. 2014 Retrovirology Discussion HIV A92E 15 19 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. The A105T mutation renders viruses with WT or A92E CA independent of the restriction on nuclear entry without preventing binding of CypA to CA. 2014 Retrovirology Discussion HIV A105T;A92E 4;46 9;50 Capsid;Capsid 51;140 53;142 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. To understand if CypA protein levels explain the different sensitivity of A92E to CsA in different cell lines the CypA protein levels were measured in 8 cell lines where A92E behaved differently in presence of CsA (Figure 9). 2014 Retrovirology Discussion HIV A92E;A92E 74;170 78;174 24479545 Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Using a recently optimized PCR assay to quantify HIV-1 2-LTR circles, it was determined here that CsA stimulates replication of the A92E CA mutant, and to a lesser extent the WT virus, at a step between the formation of the viral cDNA and its transport into the nucleus. 2014 Retrovirology Discussion HIV A92E 132 136 LTR;Capsid 57;137 60;139 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Although the L74V mutation in RT reduced the in vitro replication fitness of HIV-1, this mutation does not affect the processivity of the RT enzyme. 2014 PloS one Discussion HIV L74V 13 17 RT;RT 30;138 32;140 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Despite its rarity and decreased enzymatic activity, the G196R substitution was detected in RT-SHIV isolates from 6 of 7 animals at week 4 and was present in virus from 4 of 6 animals with detectable virus load at week 30. 2014 PloS one Discussion HIV G196R 57 62 RT 92 94 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Despite the absence of drug therapy in the study animals, some of the RT-SHIV isolates demonstrated the emergence of mutations in RT known to confer drug resistance in HIV-1, such as L74V and K103N. 2014 PloS one Discussion HIV K103N;L74V 192;183 197;187 RT;RT 70;130 72;132 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Despite the emergence of K103N in those experiments, we did not detect this mutation in rebound viremia, upon cessation of therapy, in three experiments with RT-SHIV-infected macaques treated with an efavirenz-containing HAART regimen (efavirenz+PMPA+(-)-FTC or 3TC). 2014 PloS one Discussion HIV K103N 25 30 RT 158 160 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. documented the prevalence of the V75L RT mutation in treated animals. 2014 PloS one Discussion HIV V75L 33 37 RT 38 40 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Due to the exposed nature of the G196 residue and the prevalence of G196R detected from animal isolates, we hypothesize that a host factor may interact with RT at this residue and drive the selection for the G196R mutation in the foreign RT of RT-SHIV. 2014 PloS one Discussion HIV G196R;G196R 68;208 73;213 RT;RT;RT 157;238;244 159;240;246 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Future antiretroviral drug studies in rhesus macaques warrant testing RT-SHIV containing substitutions in RT such as V75L, G196R and L214F. 2014 PloS one Discussion HIV G196R;L214F;V75L 123;133;117 128;138;121 RT;RT 70;106 72;108 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G196R was also detected in RT-SHIV from 6 of 6 animals in two previous studies of RT-SHIV-infected rhesus macaques. 2014 PloS one Discussion HIV G196R 0 5 RT;RT 27;82 29;84 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. G196R was introduced into a cloned HIV-1 RT and was shown to have only 28% of the enzymatic activity of wild-type HIV-1 RT. 2014 PloS one Discussion HIV G196R 0 5 RT;RT 41;120 43;122 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. have also reported the emergence of L74V and K103N, respectively, in RT-SHIV isolated from drug-naive rhesus macaques. 2014 PloS one Discussion HIV K103N;L74V 45;36 50;40 RT 69 71 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. identified the mutations L74V or V75L (tandemly repeated leucines or valines at residues 74 and 75), G196R, L214F, K275R, and M357T. 2014 PloS one Discussion HIV G196R;K275R;L214F;L74V;M357T;V75L 101;115;108;25;126;33 106;120;113;29;131;37 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. In cultures from individual macaques, G196R was only weakly selected in PBMC from one macaque, and did not emerge in PBMC from the other macaque through five serial passages. 2014 PloS one Discussion HIV G196R 38 43 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Indeed, the K103N RT mutation in HIV-1 has little effect on viral fitness and persists once established. 2014 PloS one Discussion HIV K103N 12 17 RT 18 20 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Indeed, when an engineered G196R RT mutant was passed in rhesus PBMC, this mutation was stably maintained in vitro for the duration of four passages (Table 7). 2014 PloS one Discussion HIV G196R 27 32 RT 33 35 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. It is unclear whether APOBEC3G activity during RT-SHIV replication in CEMx174 cells contributed to the 5% accumulation of the G196R substitution present in the RT-SHIV inoculum, but this substitution was not selected for in CEMx174-passaged RT-SHIV (Table 7). 2014 PloS one Discussion HIV G196R 126 131 RT;RT;RT 47;160;241 49;162;243 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Mutation L214F, located just beyond the C-terminus of alpha-helix F is beneath the active site and may provide compensatory packing for host factor induced positioning of the helix. 2014 PloS one Discussion HIV L214F 9 14 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. observed the RT mutations L74V, K275R, M357T, and Q507H, but they did not report the appearance of G196R. 2014 PloS one Discussion HIV G196R;K275R;L74V;M357T;Q507H 99;32;26;39;50 104;37;30;44;55 RT 13 15 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. Of the nonsynonymous mutations we detected in this study, only the RT-G196R mutation was detected at a relatively high level in the original inoculum (present in 5% of the 1899 sequence reads, data not shown). 2014 PloS one Discussion HIV G196R 70 75 RT 67 69 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. reported the consistent emergence of the V75L RT mutation in the RT-SHIVmne. 2014 PloS one Discussion HIV V75L 41 45 RT;RT 46;65 48;67 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. RT-SHIV isolates from high VL animals exhibited amino acid substitutions in all domains of RT including the fingers (L74V and V75L), the palm (G196R, L214F), the thumb (K275R), and the connection (M357 R or T), as well as in RNase H (Q507H). 2014 PloS one Discussion HIV G196R;K275R;L214F;L74V;M357R;Q507H;V75L 143;169;150;117;197;234;126 148;174;155;122;204;239;130 RT;RT 0;91 2;93 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The 5% level of G196R present in the inoculum stock was not detectable by conventional bulk Sanger sequencing (data not shown). 2014 PloS one Discussion HIV G196R 16 21 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The consistent emergence of RT mutations L74V/V75L, G196R, and L214F in RT-SHIV from 3 or more of the 4 high VL animals indicates that these mutations were positively selected for in virus from these animals. 2014 PloS one Discussion HIV G196R;L214F;L74V;V75L 52;63;41;46 57;68;45;50 RT;RT 28;72 30;74 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The G196 residue rarely mutates in HIV-1 and the G196R substitution in RT is rare or non-existent in HIV-1. 2014 PloS one Discussion HIV G196R 49 54 RT 71 73 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The G196R mutation in RT did not emerge upon passage of RT-SHIV in human CEMx174 cells. 2014 PloS one Discussion HIV G196R 4 9 RT;RT 22;56 24;58 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The G196R substitution arises from a G to A transition mutation at the first position of a GGG glycine codon, which is an APOBEC3G mutation site characterized by the GRD sequence motif. 2014 PloS one Discussion HIV G196R 4 9 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The G196R substitution represents a major amino acid modification from a small neutral amino acid (glycine) to a large basic amino acid (arginine). 2014 PloS one Discussion HIV G196R 4 9 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. The higher activation status of T lymphocytes of mixed PBMC cultures and of infected animals may account for the putative positive selection of G196R that we observed (Table 7). 2014 PloS one Discussion HIV G196R 144 149 24498008 Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV. These researchers did not specifically report the detection of G196R in their studies whereas we consistently detected G196R and the tandem repeats of V or L at residues 74 and 75 in high virus load untreated animals. 2014 PloS one Discussion HIV G196R;G196R 63;119 68;124 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Accordingly, introducing bulky electronegative aspartate or glutamate residues for Ser124 in RSV IN abrogated mutant enzyme strand-transfer activity. 2014 Nucleic acids research Discussion HIV S124E 60 89 IN 97 99 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Accordingly, the methyl group of the HIV-1 IN mutant S119A side chain might preferentially form a van der Waals interaction with cytosine at position 7 during integration. 2014 Nucleic acids research Discussion HIV S119A 53 58 IN 43 45 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Although a subset of Arg231 mutants selected for novel integration site preferences in vitro and in cells (Figures 4 and 7), the magnitude of these effects are significantly less than the preference of PFV IN mutant R329E for cytosine at position -1. 2014 Nucleic acids research Discussion HIV R329E 216 221 IN 206 208 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Although the significant further reduction in K258E IN DNA-strand-transfer activity is consistent with a role for Lys258 in tDNA binding, the associated 3'-processing defect suggests that Lys258 might play more than one role in HIV-1 integration. 2014 Nucleic acids research Discussion HIV K258E 46 51 IN 52 54 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. It is unclear whether Asn120 in HIV-1 IN might interact directly with tDNA, or whether the relatively modest novel preferences for nucleotides at sites of N120E and N120A IN mutant integration are due to indirect effects on the neighboring Ser119 side chain. 2014 Nucleic acids research Discussion HIV N120A;N120E 165;155 170;160 IN;IN 38;171 40;173 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Moreover, HIV-1 IN mutant S119A favored cytosine and guanosine at positions 7 and -3, respectively (Figure 4), in a sense recapitulating the WT PFV IN preferences at these positions (Supplementary Figure S5). 2014 Nucleic acids research Discussion HIV S119A 26 31 IN;IN 16;148 18;150 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. PFV IN mutant A188S by contrast favored adenosine and thymidine at positions 6 and -3, respectively (Supplementary Figure S5). 2014 Nucleic acids research Discussion HIV A188S 14 19 IN 4 6 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. R231E and K258E substitutions in HIV-1 IN also yielded significant reductions in DNA strand transfer activity (Figures 2 and 3). 2014 Nucleic acids research Discussion HIV K258E;R231E 10;0 15;5 IN 39 41 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. R231E IN displayed novel preferences for A/C and T/G at positions 0 and 4, respectively, whereas K258E IN did not select for significant nucleotide differences from the WT integration sequence (Figure 4 and Supplementary Figure S1). 2014 Nucleic acids research Discussion HIV K258E;R231E 97;0 102;5 IN;IN 6;103 8;105 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The in vitro nucleotide site preferences of S230N and N232R mutant INs did not vary from the WT, indicating that neither of these residues is likely to contact tDNA bases during integration. 2014 Nucleic acids research Discussion HIV N232R;S230N 54;44 59;49 IN 67 70 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The K258A IN mutation like K258E (Figure 6) reduced HIV-1 single-round infectivity >100-fold. 2014 Nucleic acids research Discussion HIV K258A;K258E 4;27 9;32 IN 10 12 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The R329E mutation in PFV IN severely reduced DNA-strand-transfer activity, and the mutant integration sites revealed a significant novel preference for cytosine at position -1. 2014 Nucleic acids research Discussion HIV R329E 4 9 IN 26 28 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. The virtual lack of D229R IN concerted integration activity precluded its site analysis. 2014 Nucleic acids research Discussion HIV D229R 20 25 IN 26 28 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. We note that one HIV-1 intasome model, in particular, yielded a shift in the register of CTD beta strands, such that residues E246GAVVIQ situated between beta1 and beta2. 2014 Nucleic acids research Discussion HIV E246A;E246G;E246I;E246Q;E246V 126;126;126;126;126 136;136;136;136;136 24520116 Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. While the R231E mutant enzyme retained the WT level of 3'-processing activity, K258E IN displayed ~3 fold 3'-processing defect (Figure 2). 2014 Nucleic acids research Discussion HIV K258E;R231E 79;10 84;15 IN 85 87 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. However, the V47A mutation does not decrease phenotypic susceptibility to darunavir. 2014 AIDS (London, England) Discussion HIV V47A 13 17 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. In our study, the Q151M mutation was not associated with a specific dual or triple-NRTI regimen failure. 2014 AIDS (London, England) Discussion HIV Q151M 18 23 NRTI 83 87 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. In the other two cases, we observed a combination of I84V and L90M mutations, resulting in 3.3-fold increased resistance to darunavir. 2014 AIDS (London, England) Discussion HIV I84V;L90M 53;62 57;66 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Lopinavir should be used as a first-line therapy to guarantee, in cases of a V47A mutation, the possibility of using a potent second-line therapy with darunavir or saquinavir associated with integrase inhibitors. 2014 AIDS (London, England) Discussion HIV V47A 77 81 IN 191 200 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Regarding NRTI drug class, we found common profiles of genotypic resistance to HIV-2, with a high proportion of Q151M, K65R, and M184V mutations. 2014 AIDS (London, England) Discussion HIV K65R;M184V;Q151M 119;129;112 123;134;117 NRTI 10 14 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Regarding protease inhibitor drug class, the V47A resistance mutation was selected in one-third of virological failures that occurred in patients who received a first-line ART that contained lopinavir. 2014 AIDS (London, England) Discussion HIV V47A 45 49 PR 10 18 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. These in-vivo findings confirm in-vitro phenotypic data, which show a significant increase in phenotypic resistance to lopinavir of the V47A site-directed mutant. 2014 AIDS (London, England) Discussion HIV V47A 136 140 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. Two of the four Q151M-mutated viruses also harbored the V111I mutation, and it has been previously shown that when Q151M was selected with the V111I mutation, a decrease in susceptibility to all NRTIs was observed. 2014 AIDS (London, England) Discussion HIV Q151M;Q151M;V111I;V111I 16;115;56;143 21;120;61;148 NRTI 195 200 24583671 Genotypic resistance profiles of HIV-2-treated patients in West Africa. We mainly observed the I54M darunavir resistance-associated mutation, which was detected in six cases, a single mutation that resulted in 6.2-fold increased resistance to darunavir. 2014 AIDS (London, England) Discussion HIV I54M 23 27 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Acutely gene-disrupted mouse cells display impaired infection by WT and N74D HIV-1. 2014 PLoS pathogens Discussion HIV N74D 72 76 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Additionally, the N74D virus is actually hypersensitive to cyclosporine despite its apparent diversion from the hypothesized CypA-Nup358Cyp pathway, and it at the same time remains sensitive to TRIM-Nup358Cyp inhibition (, and the present study). 2014 PLoS pathogens Discussion HIV N74D 18 22 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Fourth, we analyzed the phenotypes of HIV-1 capsid mutants, including the TNPO3 interaction-defective N74D, and cyclophilin binding mutants P90A, G89A, and G89V. 2014 PLoS pathogens Discussion HIV G89A;G89V;N74D;P90A 146;156;102;140 150;160;106;144 Capsid 44 50 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. Fusions of mouse Nup358Cyp or human Nup358Cyp to owl monkey TRIM equivalently inhibited both WT and N74D HIV-1. 2014 PLoS pathogens Discussion HIV N74D 100 104 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. In HeLa cells and monocyte-derived macrophages (MDM), differential effects between wild type HIV-1 and such viruses led to the proposal that a sequential CypA-Nup358 CHD interaction regulates core uncoating and that the failure of P90A HIV-1 to propagate in MDM (and the block imposed in these cells by CsA) may be due to inability to access this pathway. 2014 PLoS pathogens Discussion HIV P90A 231 235 24586169 A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. While the N74D virus replicates poorly in macrophages, and this has been interpreted as consistent with use of a Nup358-independent nuclear import pathway, a recent study suggested that this block in macrophages is instead due to an earlier block, prior to reverse transcription. 2014 PLoS pathogens Discussion HIV N74D 10 14 RT 257 278 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. For example K103N and Y181C mutations almost have no influence on the strains, and Y181C mutation even confers the virus better replication capability compared to the wild-type strain. 2014 PloS one Discussion HIV K103N;Y181C;Y181C 12;22;83 17;27;88 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. M41L often occurred together with T215Y mutation, and caused high resistance to AZT and d4T. 2014 PloS one Discussion HIV T215Y;M41L 34;0 39;4 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. Results from the HIV-1 drug resistance mutation research by the International AIDS Society-USA (updated in March 2013) have revealed that PI resistance mutation sites are L10I, K20M, V32I, M36I, M46I/L, I47V/A, I50V, Q58E, A71V, G73S, V82A/F/T, I84V, L89V,L90M; NRTIs resistance mutations are M41L, A62V, K65R, D67N, K70E/R, Y115F, M184V/I, L210W, T215Y/F, K219Q/E; and nNRTIs resistance mutations are V90I, L100I, K101E/P, K103N/S, V106A/I/M, E138A/G, Y181C/I/V, Y188C/L, G190S/A, M230L. 2014 PloS one Discussion HIV A62V;A71V;D67N;E138A;E138G;G190A;G190S;G73S;I47A;I47V;I50V;I84V;K101E;K101P;K103N;K103S;K20M;K219E;K219Q;K65R;K70E;K70R;L100I;L10I;L210W;L89V;L90M;M184I;M184V;M230L;M36I;M41L;M46I;M46L;Q58E;T215F;T215Y;V106A;V106I;V106M;V32I;V82A;V82F;V82T;V90I;Y115F;Y181C;Y181I;Y181V;Y188C;Y188L 299;223;311;444;444;473;473;229;203;203;211;245;415;415;424;424;177;357;357;305;317;317;408;171;341;251;256;332;332;482;189;293;195;195;217;348;348;433;433;433;183;235;235;235;402;325;453;453;453;464;464 303;227;315;451;451;480;480;233;209;209;215;249;422;422;431;431;181;364;364;309;323;323;413;175;346;255;260;339;339;487;193;297;201;201;221;355;355;442;442;442;187;243;243;243;406;330;462;462;462;471;471 NNRTI;NRTI;PI 370;262;138 376;267;140 AIDS 78 82 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. T215Y replaced T215F, which changed intermediate resistance to DDI to low resistance. 2014 PloS one Discussion HIV T215F;T215Y 15;0 20;5 24586665 Characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province, China. When K103N and V108I mutations happened together, they caused high resistance to EFV and NVP. 2014 PloS one Discussion HIV K103N;V108I 5;15 10;20 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. Although our results are based on a small number of observations (K65R was only observed in one individual) and interpreted cautiously, the associations with TAMs and K65R have been reported previously, but this is, to our knowledge, the first report of an effect of Y115F. 2014 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K65R;Y115F 66;167;267 71;171;272 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. However, we did find that the presence of TAMs, K65R and Y115F were independent predictors of increased etravirine susceptibility. 2014 The Journal of antimicrobial chemotherapy Discussion HIV K65R;Y115F 48;57 52;62 24633208 Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. These sensitizing effects outweighed, at group level, an increase in etravirine resistance related to N348I. 2014 The Journal of antimicrobial chemotherapy Discussion HIV N348I 102 107 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Collectively, the alternative approach suggests that the known capsid-interacting proteins are unlikely to determine CsA-dependence of the A92E mutant. 2014 PloS one Discussion HIV A92E 139 143 Capsid 63 69 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Evidence from heterokaryon analysis suggests that a dominant-acting CypA-dependent host factor inhibits A92E infection in HeLa cells. 2014 PloS one Discussion HIV A92E 104 108 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. However, expression levels of CPSF6 in permissive and non-permissive cell lines were similar in our study (Table 4), thus variations in its expression do not correlate with the cell-dependence of infection by the HIV-1-A92E mutant. 2014 PloS one Discussion HIV A92E 219 223 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. However, the gene expression data showed a negative correlation between CYPA expression and CsA- dependence of the A92E mutant. 2014 PloS one Discussion HIV A92E 115 119 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Interestingly, the N74D/A92E double mutant is resistant to CPSF6-358 restriction, suggesting that N74D mutation rescues A92E presumably by preventing CPSF6 binding. 2014 PloS one Discussion HIV A92E;A92E;N74D;N74D 24;120;19;98 28;124;23;102 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Like wild-type HIV-1, A92E mutant is inhibited by CPSF6-358. 2014 PloS one Discussion HIV A92E 22 26 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Moreover, a recent study demonstrated that CypA-CA interaction inhibited nuclear entry of A92E and increased the levels of pelletable CA protein in HeLa cells. 2014 PloS one Discussion HIV A92E 90 94 Capsid;Capsid 48;134 50;136 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Moreover, infection by another CsA-dependent mutant T54A is rescued by addition of A105T, which is present in the CA binding site for CPSF6 and confers resistance to CPSF6-358. 2014 PloS one Discussion HIV A105T;T54A 83;52 88;56 Capsid 114 116 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Nevertheless, our results do not provide clear evidence for involvement of any of the 26 genes analyzed here in CsA enhancement of infection by HIV-1-A92E. 2014 PloS one Discussion HIV A92E 150 154 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Our approach was mainly driven by the observation that the magnitude of CsA-dependence of A92E was ~3-fold higher in HeLa cells than in other non-permissive cell types. 2014 PloS one Discussion HIV A92E 90 94 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Our data showed that depletion of at least nine genes resulted in 1.7-2.7-fold increase in A92E infectivity in the absence of CsA and 1.4-2.0-fold decrease in CsA dependence. 2014 PloS one Discussion HIV A92E 91 95 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. reported that the A92E mutant capsid undergoes more rapid uncoating in HeLa cells than in Jurkat cells, suggesting that CypA may inhibit this virus by destabilizing the capsid. 2014 PloS one Discussion HIV A92E 18 22 Capsid;Capsid 30;169 36;175 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Some studies have suggested that CypA levels dictate the CsA-dependent phenotype of the A92E mutant. 2014 PloS one Discussion HIV A92E 88 92 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. The authors suggested that a dominant-acting restriction factor restricts the A92E mutant by stabilizing the viral capsid in a CypA-dependent manner. 2014 PloS one Discussion HIV A92E 78 82 Capsid 115 121 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. The CA mutants A92E and G94D were originally isolated as CypA-independent mutants by serial passage of wild-type HIV-1 in HeLa cells. 2014 PloS one Discussion HIV A92E;G94D 15;24 19;28 Capsid 4 6 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. The N74D substitution in CA renders the virus resistant to CPSF6-358 by inhibiting binding of CPSF6-358 to the capsid. 2014 PloS one Discussion HIV N74D 4 8 Capsid;Capsid 111;25 117;27 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. We expected a reversal of A92E phenotype when the putative restriction factor is depleted. 2014 PloS one Discussion HIV A92E 26 30 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. We grouped cell lines based on their permissivity to HIV-1-A92E infection and then compared the mean levels of gene expression in permissive versus non-permissive cell types to generate a ranked list of candidate genes. 2014 PloS one Discussion HIV A92E 59 63 24663101 Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. We identified another human T cell line, CEM, in which the A92E mutant requires CsA for infection. 2014 PloS one Discussion HIV A92E 59 63 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Finally, the IG insertion and P16R mutation, either alone or in combination, is known to render subtype C Env completely non-functional for HIV-1 entry into cells expressing either CCR5 or CXCR4, and additional mutations in V1 and/or V3 was likely be required to exert an influence on CXCR4 usage. 2014 PloS one Discussion HIV P16R 30 34 Env 106 109 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. However, IG insertion either alone or in combination with Q18R and/or S11R was unable to change viral coreceptor tropism (NL4-3/M7V3 to NL4-3/M9V3). 2014 PloS one Discussion HIV Q18R;S11R 58;70 62;74 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. In previous studies for subtype B, mutations such as S11R, A22T, and D25Q or D25R alone within the V3 were the minimal requirement for production of SI viruses. 2014 PloS one Discussion HIV A22T;D25Q;D25R;S11R 59;69;77;53 63;73;81;57 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Six of seven dual-tropic mutants (NL4-3/M10V3 to NL4-3/M15V3) shared the same mutations (IG insertion and P16R mutation), and another one (NL4-3/M16V3) contained MG insertion and S11R mutation. 2014 PloS one Discussion HIV P16R;S11R 106;179 110;183 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. Therefore, IG insertion and P16R or MG insertion and S11R mutation could confer CRF07_BC V3 with CXCR4-using characteristics. 2014 PloS one Discussion HIV P16R;S11R 28;53 32;57 24676404 Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China. These results suggest that the effects of IG insertion and P16R mutation or MG insertion and S11R mutation on CXCR4 usage are context dependent, and additional mutations are needed to compensate for these fitness-reducing alterations. 2014 PloS one Discussion HIV P16R;S11R 59;93 63;97 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. A recent study suggested that T97A provides no additional resistance to viruses carrying the N155H mutation, but may improve the fitness of enzymes that would otherwise be catalytically impaired. 2014 PloS one Discussion HIV N155H;T97A 93;30 98;34 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Besides E92Q, we also found two other substitutions at residue E92: E92A, a mutation less frequently described at this residue, was observed at two of the N155H-mutated viruses but, similarly to what happens with T97A, apparently provides no additional resistance to the virus; and the atypical substitution E92G was observed once in association with the N155H pathway, as previously documented. 2014 PloS one Discussion HIV E92A;E92G;E92Q;N155H;N155H;T97A 68;308;8;155;355;213 72;312;12;160;360;217 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Both E92A (GCA) and E92G (GGA) are not transitional amino acids from the wild-type E92 (GAA) to E92Q [CA(A/G)], as we confirmed through the analysis of their nucleotide sequences, so we can speculate that these can be true resistance mutations. 2014 PloS one Discussion HIV E92A;E92G;E92Q 5;20;96 9;24;100 Capsid 102 104 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. But disparate observations have been made on this matter by different HIV-2 study groups: one group agreed with our results and reported no switch of genotypic resistance profiles in the HIV-2 IN, but another group reported the switch from the N155H to the Y143C resistance pathway by both population and clonal sequencing. 2014 PloS one Discussion HIV N155H;Y143C 244;257 249;262 IN 193 195 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. But it may also be a late stage evolution of the N155H pathway. 2014 PloS one Discussion HIV N155H 49 54 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. E92Q was observed in our dataset either in association with N155H, or with T97A. 2014 PloS one Discussion HIV N155H;T97A;E92Q 60;75;0 65;79;4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Further studies are necessary to elucidate the individual impact of Q91R on HIV-2 resistance to RAL, and on the replicative capacity of the virus. 2014 PloS one Discussion HIV Q91R 68 72 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Furthermore, the de-selection of N155H occurs after the longest exposure to raltegravir (35 months) in our dataset, suggesting that despite the high level of RAL resistance conferred by this mutation, the impairment it causes in viral replication may lead to its replacement by other substitutions that allow a more efficient trade-off between acquisition of resistance and fitness costs. 2014 PloS one Discussion HIV N155H 33 38 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In addition to these two major (Q148R and N155H) and two minor (E92Q and T97A) RAL resistance mutations, other minor mutations also associated with RAL resistance in HIV-1 were observed in HIV-2 patients failing RAL-containing regimens (V151I and D232N), along with several novel mutations previously unreported in HIV-1 or HIV-2. 2014 PloS one Discussion HIV D232N;E92Q;N155H;Q148R;T97A;V151I 247;64;42;32;73;237 252;69;47;38;77;243 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In line with previous reports, the A153G substitution was always detected in the same genotype as N155H, indicating a preferential association with the 155 mutational pathway, and suggesting that this double mutation may confer higher levels of resistance to RAL than the N155H single mutant. 2014 PloS one Discussion HIV A153G;N155H;N155H 35;98;272 40;103;277 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In our dataset, this pathway seems to be the preferential towards the development of RAL resistance in HIV-2 group A viruses, since N155H was the predominant mutation selected in these patients, clearly outnumbering Q148R which was observed only in one patient. 2014 PloS one Discussion HIV N155H;Q148R 132;216 137;221 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In our sequences from INSTI-naive patients, we observed that some polymorphisms changed their prevalence according to prior ARV (NRTI/PI) exposure: V19M and L58V significantly increased their frequency in NRTI/PI-treated patients, while E246D and M277L significantly decreased their frequency in this group. 2014 PloS one Discussion HIV E246D;L58V;M277L;V19M 237;157;247;148 242;161;252;152 INSTI;NRTI;NRTI;PI;PI 22;129;205;134;210 27;133;209;136;212 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In the present study, of the HIV-1 RAL signature mutations already described in HIV-2, only N155H and Q148R were observed. 2014 PloS one Discussion HIV N155H;Q148R 92;102 97;107 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In the two patients who did not select any of these, we only observed E92Q - T97A mutations. 2014 PloS one Discussion HIV E92Q;T97A 70;77 74;81 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In this patient, we could see the initial selection of N155H - Q91R, followed by the replacement of Q91R by E92Q and K46R, and later by the addition of T97A and N160K, with the simultaneous selection against mutation at position N155. 2014 PloS one Discussion HIV E92Q;K46R;N155H;N160K;Q91R;Q91R;T97A 108;117;55;161;63;100;152 112;121;60;166;67;104;156 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. In two other patients, viruses selected and maintained the E92Q - T97A pattern without any major mutation. 2014 PloS one Discussion HIV E92Q;T97A 59;66 63;70 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Instead, we found Q148R, which is sufficient to induce phenotypic HIV-2 RAL resistance by itself. 2014 PloS one Discussion HIV Q148R 18 23 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. It is known that this secondary mutation increases the level of resistance to RAL of HIV-2 mutants in a Y143C- or N155H-resistant background, playing a more important role in the HIV-2 than in the HIV-1 context. 2014 PloS one Discussion HIV N155H;Y143C 114;104 119;109 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. K46R was always selected in N155H-carrying genotypes, and may constitute a secondary mutation specific to the 155 resistance pathway in HIV-2. 2014 PloS one Discussion HIV N155H;K46R 28;0 33;4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Mutation G140S, usually selected with Q148R to mitigate the fitness costs incurred by this primary mutation, was not observed in our study, probably due to the short exposure time of the patient to RAL (only 5 months). 2014 PloS one Discussion HIV G140S;Q148R 9;38 14;43 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Mutation K46R, however, was selected in patients with longitudinal data and persisted, being apparently fixated in the virus genome. 2014 PloS one Discussion HIV K46R 9 13 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Mutation Q148H, the most frequently observed in HIV-1 at this residue was not detected in our dataset. 2014 PloS one Discussion HIV Q148H 9 14 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Our results suggest that T97A may have the same role in viruses carrying the E92Q mutation, although further studies are necessary to confirm this hypothesis. 2014 PloS one Discussion HIV E92Q;T97A 77;25 81;29 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Since in one case we observed a de-selection of the N155H mutation under therapy in a compliant patient, we can speculate that this might be a late stage evolution of the N155H pathway. 2014 PloS one Discussion HIV N155H;N155H 52;171 57;176 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. T97A was always selected in E92Q-carrying viruses, once also with N155H. 2014 PloS one Discussion HIV E92Q;N155H;T97A 28;66;0 32;71;4 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. The Q91R substitution was detected in a N155H carrying genotype. 2014 PloS one Discussion HIV N155H;Q91R 40;4 45;8 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. The T97A - N155H association has been previously reported in HIV-2. 2014 PloS one Discussion HIV N155H;T97A 11;4 16;8 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Therefore, we can speculate that the accumulation of mutations E92Q, T97A and, eventually, K46R and N160K in this patient may be sufficient to ensure resistance to RAL without the fitness costs incurred by mutation N155H. 2014 PloS one Discussion HIV E92Q;K46R;N155H;N160K;T97A 63;91;215;100;69 67;95;220;105;73 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. This disagrees with what others have reported about the N155H pathway being observed only in patients infected with HIV-2 group B viruses. 2014 PloS one Discussion HIV N155H 56 61 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. This patient constitutes an interesting case for several reasons: it was the only patient where we could observe the replacement of pre-existing mutations by new ones; it was the first time that Q91R, a mutation never reported in HIV-1, was associated with the 155 pathway; and it was the only case where we could see the selection against major mutation N155H, albeit still under RAL pressure, and its replacement with T97A - N160K. 2014 PloS one Discussion HIV N155H;N160K;Q91R;T97A 355;427;195;420 360;432;199;424 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. This seems to suggest that E92Q, coupled with T97A, may be sufficient to elicit resistance to RAL in HIV-2, albeit to a lesser extent than N155H or Q148R, as previously demonstrated in vitro in the HIV-1 IN. 2014 PloS one Discussion HIV E92Q;N155H;Q148R;T97A 27;139;148;46 31;144;153;50 IN 204 206 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. To date, this mutation has rarely been reported, and, when so, it was either associated with the 143 pathway, together with T97A, or associated with the recently described mutation I175M and conferring high levels of resistance to RAL in vitro . 2014 PloS one Discussion HIV I175M;T97A 181;124 186;128 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. To our knowledge, this is the first time that Q91R is associated with the 155 pathway in HIV-2. 2014 PloS one Discussion HIV Q91R 46 50 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Treatment failure of HIV-2 RAL regimens seems to be associated with the emergence of resistance mutations via two main resistance pathways, stemming from N155H and Q148R. 2014 PloS one Discussion HIV N155H;Q148R 154;164 159;169 24681625 HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen. Viruses from the remaining patients that selected the N155H mutation maintained it over time, as previously described by others. 2014 PloS one Discussion HIV N155H 54 59 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. However, one of the virological failure also carried K65R; and the difference in virological outcome of these patients could be due to modulation of fitness cost by mutational interactions. 2014 BMC infectious diseases Discussion HIV K65R 53 57 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. In a study conducted in Gondar, only two mutations (V75I and G190A) were detected among 92 ART-naive patients in 2003, before ART roll out. 2014 BMC infectious diseases Discussion HIV G190A;V75I 61;52 66;57 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. In three of nine participants with HIVDR mutations at baseline, exposure to a failing regimen during 6 months was associated with the emergence of additional mutations under drug pressure, including M184V/I. 2014 BMC infectious diseases Discussion HIV M184I;M184V 199;199 206;206 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. The most frequent NRTI mutation (M184V) and NNRTI mutations (K103N) described in this study are known to be common in cases of treatment failure. 2014 BMC infectious diseases Discussion HIV K103N;M184V 61;33 66;38 NNRTI;NRTI 44;18 49;22 24708645 Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia. This may be due to the K65R mutation that can impair replicative fitness of the virus. 2014 BMC infectious diseases Discussion HIV K65R 23 27 24729604 HIV-1 drug mutations in children from northern Tanzania. Another interesting finding was a strain with the Y181C mutation from a child born to an HIV-1-infected mother, both being antiretroviral naive. 2014 The Journal of antimicrobial chemotherapy Discussion HIV Y181C 50 55 HIV infections 89 103 24729604 HIV-1 drug mutations in children from northern Tanzania. K103N was the second most predominant mutation, conferring high-level resistance to nevirapine and efavirenz. 2014 The Journal of antimicrobial chemotherapy Discussion HIV K103N 0 5 24729604 HIV-1 drug mutations in children from northern Tanzania. The detection of isolates with T215S in our cohort indicates the presence of drug selective pressure and strongly suggests resistant viruses. 2014 The Journal of antimicrobial chemotherapy Discussion HIV T215S 31 36 24729604 HIV-1 drug mutations in children from northern Tanzania. The mutation M184V was detected in one child who was not on a regimen containing lamivudine. 2014 The Journal of antimicrobial chemotherapy Discussion HIV M184V 13 18 24729604 HIV-1 drug mutations in children from northern Tanzania. The Y181C mutation was detected in two-thirds of the cases and this mutation causes high-level resistance to nevirapine, 2-fold decreased susceptibility to efavirenz and 5-fold decreased susceptibility to etravirine and rilpivirine. 2014 The Journal of antimicrobial chemotherapy Discussion HIV Y181C 4 9 24729604 HIV-1 drug mutations in children from northern Tanzania. We also detected one virus strain with dual-class resistance: Y188L for NNRTIs and M184V for NRTIs. 2014 The Journal of antimicrobial chemotherapy Discussion HIV M184V;Y188L 83;62 88;67 NNRTI;NRTI 72;93 78;98 24729604 HIV-1 drug mutations in children from northern Tanzania. We detected two mutations, Y188L and G190A, in addition to other NNRTI-associated mutations, which cause high-level resistance to nevirapine, efavirenz and rilpivirine. 2014 The Journal of antimicrobial chemotherapy Discussion HIV G190A;Y188L 37;27 42;32 NNRTI 65 70 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Among PrEP users with preexisting infection in other trials, K65R appeared after 4 weeks of TDF PrEP in 1 person, and after 7 months of FTC/TDF PrEP in another. 2014 The Journal of infectious diseases Discussion HIV K65R 61 65 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Bulk genotypic and phenotypic resistance assays revealed FTC-associated mutations (M184V or I) exclusively in participants exposed to FTC/TDF during acute infection, of which 1 had confirmed WT virus at entry. 2014 The Journal of infectious diseases Discussion HIV M184V 83 89 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. In GS-934, a randomized study of FTC/TDF/efavirenz (EFV) versus 3TC/TDF/EFV in infected ART-naive subjects, 2/19 developed M184V or I while none developed K65R or K70E after treatment for a median of 16 weeks postvirologic failure. 2014 The Journal of infectious diseases Discussion HIV K65R;K70E;M184V 155;163;123 159;167;128 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Long-term persistence of K103N is detected as minor variants in untreated infants exposed to single-dose nevirapine at birth. 2014 The Journal of infectious diseases Discussion HIV K103N 25 30 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. Of the 48 infected participants randomized to FTC/TDF, minor variant FTC-selected DR (M184I) was detected in 2 participants, 1 by qMVA (0.53%) and another by deep sequencing (0.75%), of which only the former had detectable FTC within the estimated infection window. 2014 The Journal of infectious diseases Discussion HIV M184I 86 91 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. One subject who had detectable HIV-1 RNA when starting PrEP rapidly developed FTC resistance; his drug concentrations were TFV-DP 18.7 fmol/106 PBMCs and FTC-TP 0.95 pmol/106 PBMCs at the seroconversion visit 4 weeks later, by which time M184V was selected. 2014 The Journal of infectious diseases Discussion HIV M184V 238 243 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The absence K65R or K70E in iPrEx may be due to insufficient duration of TDF exposure. 2014 The Journal of infectious diseases Discussion HIV K65R;K70E 12;20 16;24 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The contribution of archived, low-frequency M184V/I in the proviral DNA reservoir to treatment response is not known. 2014 The Journal of infectious diseases Discussion HIV M184I;M184V 44;44 51;51 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The mutations M184VI confer hypersusceptibility to ZDV and TDF, raising the possibility of successful ZDV- or TDF-based dual NRTI regimens combined with a fully active NNRTI or integrase inhibitor, thus sparing 2nd-line boosted PI-based regimens. 2014 The Journal of infectious diseases Discussion HIV M184I;M184V 14;14 20;20 IN;NNRTI;NRTI;PI 177;168;125;228 186;173;129;230 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. The response to regimens containing FTC or lamivudine (3TC) for viruses harboring isolated M184VI mutations is difficult to predict, although use of a boosted PI is an option to minimize the risk of virological failure. 2014 The Journal of infectious diseases Discussion HIV M184I;M184V 91;91 97;97 PI 159 161 24740633 HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. This is consistent with our findings measuring the time-course of transmitted M184V reversion and WT outgrowth in ARV-naive subjects, and reflects the impaired replication capacity in viruses carrying FTC-selected mutations. 2014 The Journal of infectious diseases Discussion HIV M184V 78 83 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. According to Stanford HIV resistance database, the mutations of I132L, T139K and T139R were rare events (0.11%, 0.57% and 4%, respectively) in B subtype under treatment, which may indicate the higher genetic barrier for these three mutations in B subtype than CRF_BC. 2014 PloS one Discussion HIV I132L;T139K;T139R 64;71;81 69;76;86 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Although it is reported that K101Q and H221Y may belong to the ETR RAMs, and H221Y was a mutation responsible for drug-resistance to Rilpivirine, our study has shown for the first time that both K101Q and H221Y mutations are associated with the increased resistance to all the four NNRTIs tested. 2014 PloS one Discussion HIV H221Y;H221Y;H221Y;K101Q;K101Q 39;77;205;29;195 44;82;210;34;200 NNRTI 282 288 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Especially, seven mutations at six positions (W88C, K101Q, I132L, R135L, T139K/R, H221Y and L228R) were completely absent in the RT of CRF_BC strains isolated from drug-naive patients. 2014 PloS one Discussion HIV H221Y;I132L;K101Q;L228R;R135L;T139K;T139R;W88C 82;59;52;92;66;73;73;46 87;64;57;97;71;80;80;50 RT 129 131 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Five mutants (K101Q, I132L, T139K/R and H221Y) among these eight mutants exhibited an increased resistance to the four NNRTIs tested. 2014 PloS one Discussion HIV H221Y;I132L;K101Q;T139K;T139R 40;21;14;28;28 45;26;19;35;35 NNRTI 119 125 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. In summary, our data suggest that I132L and T139K/R mutations that exhibited high-level resistance to NNRTIs are the rare but critical mutants associated with NNRTI-resistance in RT of CRF_BC strains that are predominantly circulating in China, while K101Q and H221Y mutations are associated with the increased resistance to all the four NNRTIs tested, although at codons 101 and 221 were reported relating to NNRTI resistance. 2014 PloS one Discussion HIV H221Y;I132L;K101Q;T139K;T139R 261;34;251;44;44 266;39;256;51;51 NNRTI;NNRTI;NNRTI;NNRTI;RT 102;159;338;410;179 108;164;344;415;181 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. It was also reported that T139K mutation could seriously impair catalytic activities of RT. 2014 PloS one Discussion HIV T139K 26 31 RT 88 90 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. K103N+T139K and G190A+T139K mutants induce an increased resistance to all four NNRTIs. 2014 PloS one Discussion HIV G190A;T139K;T139K;K103N 16;6;22;0 21;11;27;5 NNRTI 79 85 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Our study has demonstrated that the viruses with I132L and T139K/R mutations that exhibited high-level resistance to NNRTIs are the rare but critical mutants associated with NNRTI-resistance in both CRF_BC and B subtype. 2014 PloS one Discussion HIV I132L;T139K;T139R 49;59;59 54;66;66 NNRTI;NNRTI 117;174 123;179 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Particularly, H221Y were associated with Y181C and/or K103N mutations in RT of CRF_BC strains isolated from the treatment-experienced patients and K101Q showed positive interaction with M184V. 2014 PloS one Discussion HIV H221Y;K101Q;K103N;M184V;Y181C 14;147;54;186;41 19;152;59;191;46 RT 73 75 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The co-presence of H221Y, T139K or K101Q with the well-known RTI-resistance mutations K103N, G190A or Y181C may strengthen the drug-resistance effect. 2014 PloS one Discussion HIV G190A;H221Y;K101Q;K103N;T139K;Y181C 93;19;35;86;26;102 98;24;40;91;31;107 RT 61 64 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The positive interaction between K101Q and M184V is of interest and will be investigated in vitro in future time. 2014 PloS one Discussion HIV K101Q;M184V 33;43 38;48 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The potential mechanistic association between the NNRTI-resistance and the I132L and T139K/R mutations may be ascribed to the location of these mutation sites. 2014 PloS one Discussion HIV I132L;T139K;T139R 75;85;85 80;92;92 NNRTI 50 55 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. The result showed that either Y181C+H221Y or K103N+H221Y mutants exhibited significantly enhanced resistance to all the four NNRTIs tested, compared with Y181C alone and K103N alone mutants. 2014 PloS one Discussion HIV H221Y;H221Y;K103N;K103N;Y181C;Y181C 36;51;45;170;30;154 41;56;50;175;35;159 NNRTI 125 131 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. These results suggest that K101Q, T139K and H221Y are able to enhance the NNRTI-resistance mediated by those well-characterized HIV-1 mutants. 2014 PloS one Discussion HIV H221Y;K101Q;T139K 44;27;34 49;32;39 NNRTI 74 79 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. To understand the effect of our newly identified mutations combined with those known mutations, we examined the effect of the single mutation sites in combination with Y181C, G190A or K103N on viral resistance to NNRTIs. 2014 PloS one Discussion HIV G190A;K103N;Y181C 175;184;168 180;189;173 NNRTI 213 219 24743727 Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. Y181C+K101Q mutants also showed higher resistance to TMC-125, NVP and EFV than Y181C alone mutant. 2014 PloS one Discussion HIV K101Q;Y181C;Y181C 6;79;0 11;84;5 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Among double mutants found in our data set, two (K101EK+G190AG and V179D+Y181C) were assigned an intermediate resistance level and one (E138G+V179D) a low level of resistance by the Stanford HIVDB. 2014 Journal of the International AIDS Society Discussion HIV E138G;G190A;G190G;K101E;K101K;V179D;V179D;Y181C 136;56;56;49;49;67;142;73 141;62;62;56;56;72;147;78 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. Decreased RPV susceptibility has been observed in in vitro study among mutants harbouring Y181C+V179D (a six-fold reduction), V179I+Y181C (3.7-fold), L100I+V179I+Y181C (15.2-fold) and K103N+V179I+Y181C (10.5-fold). 2014 Journal of the International AIDS Society Discussion HIV K103N;L100I;V179D;V179I;V179I;V179I;Y181C;Y181C;Y181C;Y181C 184;150;96;126;156;190;90;132;162;196 189;155;101;131;161;195;95;137;167;201 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. In a study by Reinheimer et al., frequencies of the RPV drug resistance mutations from the German cohort of the Frankfurt Resistance Database were lower - E138K was found in 0.4% of sequences, Y181I/V in 0.9% and K101E in 2.4%. 2014 Journal of the International AIDS Society Discussion HIV E138K;K101E;Y181I;Y181V 155;213;193;193 160;218;200;200 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. In our group, E138A was the most common (3%), but the distribution of the IAS-USA-defined drug resistance mutations was not different across the subtypes and recombinants. 2014 Journal of the International AIDS Society Discussion HIV E138A 14 19 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. It should be observed that prevalence of the RPV key drug resistance mutations in our sample is higher than that of the K103N mutation, observed in 2.1% of cases, while etravirine resistance-associated mutations were rare (one sequence each with K238T and Y318F). 2014 Journal of the International AIDS Society Discussion HIV K103N;K238T;Y318F 120;246;256 125;251;261 24746180 Transmitted drug resistance to rilpivirine among antiretroviral-naive patients living with HIV from northern Poland. The V179I and V179D variants are not associated with a significant reduction in the RPV fold change susceptibility values. 2014 Journal of the International AIDS Society Discussion HIV V179D;V179I;V179D;V179I 15;5;14;4 20;10;19;9 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. A PEG linker was introduced onto the N-terminus of the peptide to allow it to reach E275C. 2014 Biochemistry Discussion HIV E275C 84 89 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Analysis of the reaction products via SDS-PAGE and Western blotting using an alpha-biotin antibody showed that the AE21 peptide reacted with E275C and successfully biotinylated E275C. 2014 Biochemistry Discussion HIV E275C;E275C 141;177 146;182 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. As further evidence of the specific reaction of AE21 with the E275C thiol, we tested the reaction of AE21 with WT gp120. 2014 Biochemistry Discussion HIV E275C 62 67 gp120 114 119 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Because there are no other unpaired cysteine SH groups in WT and E275C gp120 proximal to the functionally important and conformationally variable domains of gp120 around the F43 pocket, this mutant may also be used for future efforts in tethering-based strategies to screen for potential entry inhibitors that bind to gp120. 2014 Biochemistry Discussion HIV E275C 65 70 gp120;gp120;gp120 71;157;318 76;162;323 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Consistent with this assumption, a commercially available biotinylation reagent, MPB, had negligible reactivity toward E275C gp120 (Figure 3), which argues for the role of AE21-E275C binding in improving reactivity. 2014 Biochemistry Discussion HIV E275C;E275C 119;177 124;182 gp120 125 130 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Further, a maleimide moiety was introduced at the N-terminal end of the linker for selective conjugation to the E275C thiol. 2014 Biochemistry Discussion HIV E275C 112 117 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Furthermore, like WT gp120, E275C gp120 was recognized by the monoclonal antibody b12. 2014 Biochemistry Discussion HIV E275C 28 33 gp120;gp120 21;34 26;39 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Hence, a lack of WT gp120 labeling by AE21, combined with negligible labeling of E275C gp120 by MPB, provides further evidence of the specific reaction of AE21 with E275C thiol. 2014 Biochemistry Discussion HIV E275C;E275C 81;165 86;170 gp120;gp120 20;87 25;92 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Here, SPR analysis revealed that 2G12 bound to the AE21-E275C covalent complex. 2014 Biochemistry Discussion HIV E275C 56 61 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. More importantly, analysis of binding of E275C gp120 to SR07C, a surface-immobilized peptide triazole variant, showed that the peptide was able to bind to E275C with an affinity similar to that of WT gp120. 2014 Biochemistry Discussion HIV E275C;E275C 41;155 46;160 gp120;gp120 47;200 52;205 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. One would expect E275C gp120 to have a reactivity toward AE21 higher than that of nonbinding thiol-reactive molecules. 2014 Biochemistry Discussion HIV E275C 17 22 gp120 23 28 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Reaction of the AE21 affinity label with the recombinantly engineered gp120 Cys variant E275C yielded the desired covalent conjugate. 2014 Biochemistry Discussion HIV E275C 88 93 gp120 70 75 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. Surface plasmon resonance analyses showed that E275C gp120 maintained binding affinity for sCD4 and 17b, the two canonical gp120 ligands. 2014 Biochemistry Discussion HIV E275C 47 52 gp120;gp120 53;123 58;128 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. The SPR results reported here showed that indeed binding of 17b to the AE21-E275C covalent complex is completely suppressed. 2014 Biochemistry Discussion HIV E275C 76 81 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. These results demonstrated the feasibility of using E275C gp120 as a minimally altered gp120 variant containing a suitable, selective handle for peptide triazole conjugation. 2014 Biochemistry Discussion HIV E275C 52 57 gp120;gp120 58;87 63;92 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. This reinforces the argument that the AE21-E275C covalent conjugate has binding characteristics similar to those of a noncovalently bound peptide triazole-gp120 complex. 2014 Biochemistry Discussion HIV E275C 43 48 gp120 155 160 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. To evaluate binding characteristics of the PT-gp120 covalent conjugate, the purified AE21-E275C reaction product was immobilized on an SPR chip and binding to various gp120 ligands was measured. 2014 Biochemistry Discussion HIV E275C 90 95 gp120;gp120 46;167 51;172 24801282 Covalent conjugation of a peptide triazole to HIV-1 gp120 enables intramolecular binding site occupancy. We hypothesized that introducing a single cysteine at this position should lead to an expressible protein, denoted E275C gp120, which remains functional toward typical gp120 ligands. 2014 Biochemistry Discussion HIV E275C 115 120 gp120;gp120 121;168 126;173 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. 1) caused poor interaction with CBF-beta, especially W89A and I107S. 2014 PloS one Discussion HIV I107S;W89A 62;53 67;57 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Analysis of alanine or serine substitutions in HIV-1 Vif showed that G84A, 84/86-89, 88/89, W89A, L106S and I107S. 2014 PloS one Discussion HIV G84A;I107S;L106S;W89A 69;108;98;92 73;113;103;96 Vif 53 56 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Except for G84D and D104A, the mutations studied, including 84/86-89, 88/89, G84A, W89A, L106S and I107S, in the 84GxSIEW89 and L102ADQLI107 regions of HIV-1 Vif played important roles in the Vif-CBF-beta interaction. 2014 PloS one Discussion HIV D104A;G84A;G84D;I107S;L106S;W89A 20;77;11;99;89;83 25;81;15;104;94;87 Vif;Vif 158;192 161;195 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. In our study, it was noteworthy that G84D and D104 totally abolished Cul5 binding, but these mutants still retained some interaction with CBF-beta. 2014 PloS one Discussion HIV G84D 37 41 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. Therefore, it is possible that G84D and D104 directly affect the interaction of Vif with CUL5, which contributes to or stabilizes the Vif-CBF-beta interaction. 2014 PloS one Discussion HIV G84D 31 35 Vif;Vif 80;134 83;137 24810617 Identification of HIV-1 Vif regions required for CBF-beta interaction and APOBEC3 suppression. V85S and Q105A only slightly affected the interaction of Vif with CBF-beta. 2014 PloS one Discussion HIV Q105A;V85S 9;0 14;4 Vif 57 60 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. Both the presence of TAMs and K65R has an impact on the NRTI options available for 2nd and 3rd-line regimens. 2014 PloS one Discussion HIV K65R 30 34 NRTI 56 60 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. Due to the relatively low prevalence of both TAMs and K65R, the majority of children remain susceptible to AZT and TDF. 2014 PloS one Discussion HIV K65R 54 58 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. However, this finding does not significantly impact options for 2nd-line drugs, as M184V/I reduces viral fitness and often delays the development of TAMs. 2014 PloS one Discussion HIV M184I;M184V 83;83 90;90 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. More than 60% of the children exposed to PIs did not show any PI-mutation, other than the T74S polymorphism. 2014 PloS one Discussion HIV T74S 90 94 PI;PI 41;62 44;64 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The frequency of M184V/I and consequent high-level resistance to 3TC/FTC is consistent with results found in most other South African studies. 2014 PloS one Discussion HIV M184I;M184V 17;17 24;24 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. The K65R mutation was more often present in ABC-exposed children compared to those exposed to d4T, which has recently been described by Van Zyl et al. 2014 PloS one Discussion HIV K65R 4 8 24816790 High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen. This M184V/I mutation also caused intermediate resistance to ABC in more than 80% of the d4T-exposed children. 2014 PloS one Discussion HIV M184I;M184V 5;5 12;12 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. Furthermore, the A128T mutation in IN has been shown to confer marked resistance to the majority of ALLINIs. 2014 PLoS pathogens Discussion HIV A128T 17 22 IN 35 37 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. In contrast, the benzimidazole ring in KF116 is oriented perpendicular to the core pyridine ring (Figure 2), which enables this compound to avoid the steric effects of the A128T substitution seen with archetypal ALLINI BI-1001. 2014 PLoS pathogens Discussion HIV A128T 172 177 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. The planar quinoline core found in ALLINIs extends toward the Ala-128 residue and allows the evolution of HIV-1 IN A128T escape mutation. 2014 PLoS pathogens Discussion HIV A128T 115 120 IN 112 114 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. Therefore, it is possible that T124N and T174I substitutions directly affect KF116 binding, while the V165I substitution could be a compensatory mutation to restore IN function and/or stability that may be compromised by the T124N and T174I substitutions. 2014 PLoS pathogens Discussion HIV T124N;T124N;T174I;T174I;V165I 31;225;41;235;102 36;230;46;240;107 IN 165 167 24874515 A new class of multimerization selective inhibitors of HIV-1 integrase. While a single A128T mutation was sufficient to confer marked resistance to a number of ALLINIs, selection of HIV-1 variants under genetic pressure of KF116 revealed the triple T124N/V165I/T174I mutant as the predominant variant. 2014 PLoS pathogens Discussion HIV T124N;T174I;V165I;A128T 177;189;183;15 182;194;188;20 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Although Ceccherini-Silberstein reported novel mutations cluster (L74V and H221Y) frequently appears with Y181C and share with it the ability to increase NNRTI resistance , but the idiographic impact and molecular mechanism were unclear. 2014 BMC infectious diseases Discussion HIV H221Y;L74V;Y181C 75;66;106 80;71;111 NNRTI 154 159 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. At the same time, the double mutations were observed along with other NNRTIs including K101E, K101Q, V179D, V179E, K103N, and the viruses were predominant in quasispecies of 6 HIV-1 infected patients in a drug resistance surveillance cohort. 2014 BMC infectious diseases Discussion HIV K101E;K101Q;K103N;V179D;V179E 87;94;115;101;108 92;99;120;106;113 NNRTI 70 76 HIV infections 176 190 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Here, we evaluated the contribution of K101Q plus Y181C plus H221Y to resistance of NNRTIs (NVP, EFV). 2014 BMC infectious diseases Discussion HIV H221Y;K101Q;Y181C 61;39;50 66;44;55 NNRTI 84 90 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, it is interpreted in Stanford database that H221Y does not decrease susceptibility by itself but may contribute to the decrease of NNRTI susceptibility in combination with other NNRTI-resistance mutations. 2014 BMC infectious diseases Discussion HIV H221Y 53 58 NNRTI;NNRTI 140;187 145;192 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, K101Q was interpreted as a relatively non-polymorphic mutation that occurred slightly more commonly among patients receiving NNRTIs. 2014 BMC infectious diseases Discussion HIV K101Q 9 14 NNRTI 134 140 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, we observed K101Q emerge along with Y181C and H221Y, but not with K103N. 2014 BMC infectious diseases Discussion HIV H221Y;K101Q;K103N;Y181C 55;21;75;45 60;26;80;50 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. However, Y181C significantly reversed the K101Q/H221Y phenotypic susceptibility to EFV. 2014 BMC infectious diseases Discussion HIV H221Y;K101Q;Y181C 48;42;9 53;47;14 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. In EFV, H221Y increased the susceptibility while Y181C increased resistance. 2014 BMC infectious diseases Discussion HIV H221Y;Y181C 8;49 13;54 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. In the pre-study, we found the viruses carrying H221Y were commonly combined with Y181C, the same result as the one in the reference papers . 2014 BMC infectious diseases Discussion HIV H221Y;Y181C 48;82 53;87 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. In this study, we observed copresence of the two secondary mutants (K101Q and H221Y) show hypersusceptibility to EFV with a mean IC50 value of 0.54 +- 0.32nM (FC = 0.04, P<0.05), but only a 4.0-fold increase in NVP resistance. 2014 BMC infectious diseases Discussion HIV H221Y;K101Q 78;68 83;74 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. It is worth noting that triple-mutation K101Q/Y181C/H221Y only shows a less extensive increase. 2014 BMC infectious diseases Discussion HIV H221Y;K101Q;Y181C 52;40;46 57;45;51 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. It was reported that single K101Q induced a 3.2-fold NVP resistance and a 5.6-fold EFV resistance and that Y181C conferred 100-fold NVP resistance and 1.1-fold EFV resistance at the pNL4-3 background . 2014 BMC infectious diseases Discussion HIV K101Q;Y181C 28;107 33;112 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. K101Q hardly changed susceptibility of NVP and EFV, with FC value of 0.8-fold and 0.4-fold compared with wild-type respectively. 2014 BMC infectious diseases Discussion HIV K101Q 0 5 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. K101Q/H221Y double mutation showed significantly increase in AZT, 3TC, d4T resistance. 2014 BMC infectious diseases Discussion HIV H221Y;K101Q 6;0 11;5 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Moreover, Y181C was known to confer high level resistance to NVP . 2014 BMC infectious diseases Discussion HIV Y181C 10 15 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Previous studies demonstrated K101Q was not correlated with any NNRTI resistance mutations, but was the prerequisite to the presence of K103N . 2014 BMC infectious diseases Discussion HIV K101Q;K103N 30;136 35;141 NNRTI 64 69 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Regrettably, we have not observed which one first emerges during mutational pathways, Y181C or H221Y. 2014 BMC infectious diseases Discussion HIV H221Y;Y181C 95;86 100;91 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. So far, some researchers have reported the molecular mechanism between the Y181C and other mutations . 2014 BMC infectious diseases Discussion HIV Y181C 75 80 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. The result showed K101Q/Y181C/H221Y viruses led to a 1253.9-fold great increase in NVP resistance and a 5.00-fold significant increase in EFV resistance. 2014 BMC infectious diseases Discussion HIV H221Y;K101Q;Y181C 30;18;24 35;23;29 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. Then, as for NRTIs, Y181C significantly decreased the H221Y resistance. 2014 BMC infectious diseases Discussion HIV H221Y;Y181C 54;20 59;25 NRTI 13 18 24885612 Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China. We evaluated the interaction between Y181C and H221Y considering K101Q as the background. 2014 BMC infectious diseases Discussion HIV H221Y;K101Q;Y181C 47;65;37 52;70;42 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. In our previous study, we have found that the single E314G mutation in the V3 crown tip of ZP6248 could partially restore its infectivity in CCR5+ cells, but reduced its ability to replicate in GPR15+ cells. 2014 PloS one Discussion HIV E314G 53 58 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. More severe cell death was observed in cells infected with either YU2.6248V3-G306A or YU2.6248V3-S322A mutants. 2014 PloS one Discussion HIV G306A;S322A 77;97 82;102 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. The E314A mutant had similar phenotypes, but infected CCR5+ cells at a higher level. 2014 PloS one Discussion HIV E314A 4 9 24897520 The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain. The E314A mutant replicated in CCR5+ cells slightly better than YU2 but failed to grow in GPR15+ cells. 2014 PloS one Discussion HIV E314A 4 9 24909578 Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia. The present study did find two isolates that harbored both the dhps A581G mutation along with the quintuple mutant haplotype; this has never been described in Zambia. 2014 Malaria journal Discussion HIV A581G 68 73 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Additionally we show that mutant N260Q gp160 folds even slower than WT gp160. 2014 PloS one Discussion HIV N260Q 33 38 gp160;gp160 39;71 44;76 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Also, in our hands, introduction of R302I in the N260Q/S128N gp120 background did not increase infectivity to WT levels. 2014 PloS one Discussion HIV N260Q;R302I;S128N 49;36;55 54;41;60 gp120 61 66 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Although the infectivity of N260Q gp160 HIV could be somewhat increased by the introduction of the compensatory mutation S128N in gp160, this secondary mutation was found not to result in measurably increased expression/incorporation of the glycoprotein in the viral envelope, faster folding kinetics or improved CD4 binding. 2014 PloS one Discussion HIV N260Q;S128N 28;121 33;126 Env;gp160;gp160 267;34;130 275;39;135 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Hence, the underlying compensatory mechanism of the S128N mutation is currently not known. 2014 PloS one Discussion HIV S128N 52 57 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. However, even after long-term passaging of N260Q/S128N gp120-containing virus strains, we did not select for any additional mutation including R302I that could restore infection of the double mutant virus to WT levels. 2014 PloS one Discussion HIV N260Q;R302I;S128N 43;143;49 48;148;54 gp120 55 60 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. In contrast to our results, they observed a complete restoration of CD4 binding upon introduction of S128N. 2014 PloS one Discussion HIV S128N 101 106 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Moreover, we demonstrated that an increased lysosomal degradation of mutant N260Q HIV env glycoproteins is involved in this loss of viral infectivity. 2014 PloS one Discussion HIV N260Q 76 81 Env 86 89 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. reported the beneficial effect of the additional mutation at amino acid R302I in gp120 on mutant virus infectivity. 2014 PloS one Discussion HIV R302I;R302I 73;72 78;77 gp120 81 86 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The authors located mutation S128N in the C1 domain, and hence studied mostly the interaction of this domain with the C2 domain, which contains the N260 glycan. 2014 PloS one Discussion HIV S128N 29 34 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The loss of the N260 glycan on gp120 may affect the native conformation of uncleaved gp160, thereby inducing misfolding sensors in the Golgi apparatus, leading to increased lysosomal degradation of the N260Q mutant glycoprotein. 2014 PloS one Discussion HIV N260Q 202 207 gp120;gp160 31;85 36;90 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The N260Q and N260Q/S128N mutant virus strains produced under similar experimental conditions did not show measurable infectivity in C8166 cell cultures, regardless of the presence or absence of chloroquine during virus production (data not shown). 2014 PloS one Discussion HIV N260Q;N260Q;S128N 4;14;20 9;19;25 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The pulse-chase data indicate that at least a fraction of mutant N260Q gp160 is processed and that gp120 is shed from transfected cells. 2014 PloS one Discussion HIV N260Q 65 70 gp120;gp160 99;71 104;76 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. The Western blot analysis revealed that mutant N260Q gp160 is cleaved to a much lesser extent than wild-type gp160. 2014 PloS one Discussion HIV N260Q 47 52 gp160;gp160 53;109 58;114 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Thus, our data corroborate the hypothesis of increased lysosomal degradation due to the N260Q mutation in gp160. 2014 PloS one Discussion HIV N260Q 88 93 gp160 106 111 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. used antibodies to study the conformational changes induced by N260Q and its compensatory mutation S128N in gp160. 2014 PloS one Discussion HIV N260Q;S128N;N260Q;S128N 64;100;63;99 69;105;68;104 gp160 108 113 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. Virus, WT or mutant, produced in the presence of chloroquine contained increased levels of gp160, gp120 and gp41, which were clearly more pronounced for gp160 containing the N260Q mutation. 2014 PloS one Discussion HIV N260Q 174 179 gp120;gp160;gp160;gp41 98;91;153;108 103;96;158;112 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We have verified the hypothesis that the N260Q mutation in gp160 causes increased lysosomal degradation of gp160/gp120, by inhibiting the lysosomal degradation pathway with chloroquine, a known inhibitor of lysosomal activity. 2014 PloS one Discussion HIV N260Q 41 46 gp120;gp160;gp160 113;59;107 118;64;112 24967714 Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity. We show here that at least some N260Q gp160 is degraded in the lysosomes, which will result in decreased incorporation of gp120 and g41 into the viral envelope. 2014 PloS one Discussion HIV N260Q 32 37 Env;gp120;gp160 151;122;38 159;127;43 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. H69K (86%), M36I (81%), L89M (74%), and I93L (62%) were considered to be subtype-specific natural polymorphisms since they occur at high frequency in HIV-1 subtypes A1, C or D. 2014 PloS one Discussion HIV I93L;L89M;M36I;H69K 40;24;12;0 44;28;16;4 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. Since PIs were not used in Tanzania at the time that the samples were collected, the mutations M46I and M46L most likely represent natural polymorphisms rather than transmitted drug-resistant strains. 2014 PloS one Discussion HIV M46I;M46L 95;104 99;108 PI 6 9 25003939 HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania. Three (7%) subjects had a major mutation at the protease amino acid position 46 (M46I/L) that confers high resistance to protease inhibitors (PIs) only in combination with other mutations, and can occur among untreated persons as natural polymorphisms, as was reported previously in Tanzania among treatment-naive individuals. 2014 PloS one Discussion HIV M46I;M46L 81;81 87;87 PR;PR;PI 48;121;142 56;129;145 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. A62V a multinucleoside HIVDR mutation was seen in 1 study sequence. 2014 ISRN AIDS Discussion HIV A62V 0 4 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. All of them cause high-level resistance to nevirapine and variable resistance to efavirenz, ranging from about twofold for V106A and Y181C, sixfold for G190A, 20-fold for K103N, and more than 50-fold for Y188L. 2014 ISRN AIDS Discussion HIV G190A;K103N;V106A;Y181C;Y188L 152;171;123;133;204 157;176;128;138;209 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. E44D, an accessory mutation that generally occurs with type I pattern TAM, was seen in 1 study participant. 2014 ISRN AIDS Discussion HIV E44D 0 4 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. L100I, K101P, P225H, F227L, M230L, and K238T are secondary mutations that usually occur in combination with one of the primary NNRTI resistance mutations. 2014 ISRN AIDS Discussion HIV F227L;K101P;K238T;M230L;P225H;L100I 21;7;39;28;14;0 26;12;44;33;19;5 NNRTI 127 132 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. M230L, seen in 1 study sequence, may occur alone which decreases the susceptibility of all NNRTI including etravirine by 20-fold or more. 2014 ISRN AIDS Discussion HIV M230L 0 5 NNRTI 91 96 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. N348I a nonpolymorphic HIVDR mutation was seen in 1 study sequence which occurs in about 10% of NRTI-treated patients. 2014 ISRN AIDS Discussion HIV N348I 0 5 NRTI 96 100 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. N348I causes a twofold reduction in AZT susceptibility when it occurs in combination with multiple TAM. 2014 ISRN AIDS Discussion HIV N348I 0 5 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. Of these secondary mutations P225H (1/19) & K238T/N (2/19) were the secondary NNRTI mutation seen in our study. 2014 ISRN AIDS Discussion HIV K238N;K238T;P225H 44;44;29 51;51;34 NNRTI 78 83 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. The commonest NRTI mutation observed was M184V (8/19), which was in agreement with previous Indian studies done on ART experienced individuals. 2014 ISRN AIDS Discussion HIV M184V 41 46 NRTI 14 18 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. The most common primary NNRTI resistance mutation was K103N/S which was observed in 6 study participants (K103N-5; K103S-1), which is also the most common mutation documented in another Indian study, whereas two other Indian studies found Y181C/V & G190A and V106M & Y181C, respectively, as the commonest NNRTI mutations. 2014 ISRN AIDS Discussion HIV G190A;K103N;K103N;K103S;K103S;V106M;Y181C;Y181C;Y181V 249;54;106;54;115;259;239;267;239 254;61;111;61;120;264;246;272;246 NNRTI;NNRTI 24;305 29;310 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. The other primary NNRTI resistance mutations that were seen in our study were V106M (2/19), Y181C (1/19), Y188L (2/19), and G190A (1/19). 2014 ISRN AIDS Discussion HIV G190A;V106M;Y181C;Y188L 124;78;92;106 129;83;97;111 NNRTI 18 23 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. The Q151M complex was not seen in any of the study sequences in our study. 2014 ISRN AIDS Discussion HIV Q151M 4 9 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. The type I pattern includes the mutations M41L, L210W, and T215Y while type II pattern includes D67N, K70R, T215F, and K219Q/E. 2014 ISRN AIDS Discussion HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 96;119;119;102;48;42;108;59 100;126;126;106;53;46;113;64 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. They usually occur in combination with K103N as observed in our study. 2014 ISRN AIDS Discussion HIV K103N 39 44 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. This M184V HIVDR mutation which is the commonest and earliest HIVDR mutation to occur in lamivudine (3TC) treated individuals causes high-level resistance to lamivudine (3TC) and emtricitabine (FTC) and low-level resistance to didanosine (ddI) and abacavir (ABC) and increased susceptibility to zidovudine (AZT), stavudine (d4T), and tenofovir (TDF). 2014 ISRN AIDS Discussion HIV M184V 5 10 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. Type I TAMs were seen in 2 study sequences in our study out of which in 1 study sequence all the three type I TAMs were seen along with D67N. 2014 ISRN AIDS Discussion HIV D67N 136 140 25006528 Emergence of drug resistance in human immunodeficiency virus type 1 infected patients from pune, India, at the end of 12 months of first line antiretroviral therapy initiation. V90I was observed in 1 study sequence which is associated with decreased virologic response to etravirine in the DUET clinical trial. 2014 ISRN AIDS Discussion HIV V90I 0 4 25008864 SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma. A significant increase of risk (adjusted OR=10.5) was associated with further carriage of non-synonymous rs1800453 (A>G) and rs4148880 (A>G) alleles encoding Asp697Gly and Ile393Val mutations in TAP1, respectively. 2014 Genes and immunity Discussion HIV D697G;I393V 158;172 167;181 Asp 158 161 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Because the compensatory mutation V247I had been present in the majority of the viral population when the T242N was selected, the fitness loss caused by the T242N mutation would be readily alleviated by the preexisting V247I mutation. 2014 PloS one Discussion HIV T242N;T242N;V247I;V247I 106;157;34;219 111;162;39;224 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Both of the compensatory mutations V247I and G248A were first selected by T cell responses before the fitness-impairing T242N mutation in CH77. 2014 PloS one Discussion HIV G248A;T242N;V247I 45;120;35 50;125;40 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Conflicting results about fitness costs of the G248A mutation were reported in previous studies. 2014 PloS one Discussion HIV G248A 47 52 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. However, how it interacted with the T242N mutation and affected the viral fitness with or without the T242N mutation has not been studied. 2014 PloS one Discussion HIV T242N;T242N 36;102 41;107 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. However, this might not necessarily indicate that the T242N mutation would only be selected after the V247I and/or G248A mutation selected, since the I247 was predominant (97.28%) while A248 was frequently detected (22.08%) among subtype B sequences in the Los Alamos HIV-1 sequence database showed. 2014 PloS one Discussion HIV G248A;T242N;V247I 115;54;102 120;59;107 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. It is likely that the fitness cost of the T242N mutation and the compensatory effect of the V247I and G248A mutations were mediated by altering its interaction with CypA or other host factors important for virus replication, instead of dramatically disturbing the capsid stability or assembly. 2014 PloS one Discussion HIV G248A;T242N;V247I 102;42;92 107;47;97 Capsid 264 270 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. It took months for both the V247I and I64T reversion mutations to become fixed in the population from the first time of detection. 2014 PloS one Discussion HIV I64T;V247I 38;28 42;33 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. It was also possible that both CD8+ T cell escape mutations (R355K and G248A) could cause fitness losses which were too small to be detected by the current fitness assays. 2014 PloS one Discussion HIV G248A;R355K 71;61 76;67 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. One CD8+ T cell escape mutation (R355K) in Env was selected by the T cell responses very early during infection. 2014 PloS one Discussion HIV R355K 33 38 Env 43 46 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Our protein modeling analysis of helix 6 showed that only subtle structural differences were observed between the T/F and all three mutations (T242N, V247I and G258A) in structural models of p24. 2014 PloS one Discussion HIV G258A;T242N;V247I 160;143;150 165;148;155 p24 191 194 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Our results unexpectedly demonstrated that both weak T cell escape mutations (V247I and G248A) could partially repair the fitness loss due to the CD8+ T cell escape mutation T242N. 2014 PloS one Discussion HIV G248A;T242N;V247I 88;174;78 93;179;84 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Similar evolutionary dynamics were also observed for the reversion of the T242N mutation. 2014 PloS one Discussion HIV T242N 74 79 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. Since both the V247I and G248A mutations together could fully restore the significant fitness loss caused by the T242N mutation, the CD8+ T cell escape mutant containing both the fitness-impairing escape mutation (T242N) and compensatory mutations (V247I and G248A) could be as pathogenic as the wild type viruses. 2014 PloS one Discussion HIV G248A;G248A;T242N;T242N;V247I;V247I 25;259;113;214;15;249 30;264;118;219;20;255 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The G248A mutation also allowed the virus to partially escape from the early T cell responses. 2014 PloS one Discussion HIV G248A 4 9 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The increased dependency on CypA of the T242N mutant and compensation of the fitness loss of the T242N mutation by mutations in the CypA-binding loop, as well as the potential effect on the packing of the CypA binding loop by amino acids at position 248 support this hypothesis. 2014 PloS one Discussion HIV T242N;T242N 40;97 45;102 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The lack of measurable fitness cost for the R355K mutation was in consistent with previous observations that R355K escaped rapidly after transmission and was in a high entropy epitope. 2014 PloS one Discussion HIV R355K;R355K 44;109 49;114 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The lack of measurable fitness cost of the R355K mutation might facilitate its rapid escape kinetics in vivo and the quick predominance in the viral population throughout the follow-up period. 2014 PloS one Discussion HIV R355K 43 48 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The reversion mutation V247I, also a weak T cell escape mutation, could partially compensate the fitness loss due to the T242N mutation. 2014 PloS one Discussion HIV T242N;V247I 121;23 126;28 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The T242N mutation that alone could cause significant fitness loss was selected by a late potent T cell response targeting the TW10 epitope. 2014 PloS one Discussion HIV T242N 4 9 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. The V247I mutation was selected by the early T cell responses. 2014 PloS one Discussion HIV V247I 4 9 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. This was in agreement with our in vivo observation that the R355K mutation persisted without reversion after the T cell responses targeting the Env352-360 epitope vanished. 2014 PloS one Discussion HIV R355K 60 65 Env 144 147 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. We studied the impact of reversion and T cell escape mutations in their unmodified cognate T/F viral genome and found that reversion mutations did not cause measurable fitness gains in the cognate T/F virus but could compensate the fitness loss caused by the CD8+ T cell escape mutation T242N, and, unexpectedly, weak CD8+ T cell escape mutations could also partially compensate the fitness loss caused by the T242N mutation in the same epitope. 2014 PloS one Discussion HIV T242N;T242N 287;410 292;415 25028937 Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus. We studied two reversion mutations (V247I and I64T), but neither of them rendered the cognate T/F virus more fit as determined by the competitive PASS fitness assay. 2014 PloS one Discussion HIV I64T;V247I 46;36 50;42 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Eight specimens were collected more than one month apart of which only one showed minor discordance for Y181C. 2014 Journal of virological methods Discussion HIV Y181C 104 109 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Five specimens showed significant levels of non-correlation, two for Y181C and three for K103N. 2014 Journal of virological methods Discussion HIV K103N;Y181C 89;69 94;74 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. In this study we have shown that the detection of minority species of Y181C and K103N can be accurately measured by AS-PCR and UDPS. 2014 Journal of virological methods Discussion HIV K103N;Y181C 80;70 85;75 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Previous studies have reported significant correlations in frequency and copy number of K103N mutants quantified in parallel by AS-PCR and UDPS technologies in 11 adult patients treated with efavirenz (EFV) as part of the ANRS 106 trial, and concordant UDPS and AS-PCR results in 20 infants exposed to sdNVP for pMTCT when resistance is present at high frequencies only. 2014 Journal of virological methods Discussion HIV K103N 88 93 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. Specifically, our data were significantly correlated for detection of both mutations (p<0.0001), with correlation coefficients of 0.94 and 0.89 for Y181C and K103N respectively. 2014 Journal of virological methods Discussion HIV K103N;Y181C 158;148 163;153 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. The kappa statistic for detection of Y181C was 0.8739 (standard error 0.0973), with very good strength of agreement between the AS-PCR and UDPS assays, and 0.2962 (standard error 0.0974) for K103N indicating only fair agreement between the two assays for the latter mutation. 2014 Journal of virological methods Discussion HIV K103N;Y181C 191;37 196;42 25034127 Concordance between allele-specific PCR and ultra-deep pyrosequencing for the detection of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. This statistic may have been unduly influenced by the low number of K103N positive results (n=14). 2014 Journal of virological methods Discussion HIV K103N 68 73 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. A98G and V179E were excluded from the WHO list of SDRMs because of high occurrence in viruses from treatment-naive individuals. 2014 AIDS research and therapy Discussion HIV V179E;A98G 9;0 14;4 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. A98G has been shown to confer low-level resistance against EFV and NVP, and V179D in CRF01_AE/CRF07_BC recombinant viruses has been shown to confer low-level resistance against EFV and intermediate level resistance against NVP, while V179D in CRF01_AE viruses does not affect resistance to any RT drugs (data not published). 2014 AIDS research and therapy Discussion HIV V179D;V179D;A98G 76;234;0 81;239;4 RT 294 296 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. For example, L10V, V11I/V, L33F, T69A/N/S, and P236L were present only in individuals with CRF01_AE strains. 2014 AIDS research and therapy Discussion HIV L10V;L33F;P236L;T69A;T69N;T69S;V11I;V11V 13;27;47;33;33;33;19;19 17;31;52;41;41;41;25;25 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. However, some NNRTI-related mutations, such as K103N, can persist for a long period of time. 2014 AIDS research and therapy Discussion HIV K103N 47 52 NNRTI 14 19 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. Other commonly observed mutations were T69A/N/S, V179E, L10I/L/V, V11I/V, L33F, and A71A/T/V; none of these mutations is known to confer drug resistance to NRTIs, NNRTIs, or PIs. 2014 AIDS research and therapy Discussion HIV A71A;A71T;A71V;L10I;L10L;L10V;L33F;T69A;T69N;T69S;V11I;V11V;V179E 84;84;84;56;56;56;74;39;39;39;66;66;49 92;92;92;64;64;64;78;47;47;47;72;72;54 NNRTI;NRTI;PI 163;156;174 169;161;177 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. Specific mutations included L210W, Y181C, and G190A, which confers different levels of drugs resistance. 2014 AIDS research and therapy Discussion HIV G190A;L210W;Y181C 46;28;35 51;33;40 25035709 The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China. The present study found that substitutions of A71T/V and L10I often appeared in CRF07_BC, which was different from other studies reporting that substitutions of A71T/V often appeared in B viruses, whereas L10I was frequently discovered in CRF01_AE viruses. 2014 AIDS research and therapy Discussion HIV A71T;A71T;A71V;A71V;L10I;L10I 46;161;46;161;57;205 52;167;52;167;61;209 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. Early after failure these viruses carry a single NNRTI mutation often combined with the M184V/I. 2014 BMC infectious diseases Discussion HIV M184I;M184V 88;88 95;95 NNRTI 49 54 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. However, our phylogenetic analyses indicated that an increase in transmitted NNRTI resistance did not occur within only a few large phylogenetic clusters thus suggesting that TDR with K103N originated from different sources. 2014 BMC infectious diseases Discussion HIV K103N 184 189 NNRTI 77 82 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. In contrast, the K103N has a limited effect on viral replication capacity and persist for long periods after transmission and strains with this mutation are therefore also transmitted to others (onward transmission). 2014 BMC infectious diseases Discussion HIV K103N 17 22 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. M184V has a strong effect on replication capacity and if transmitted, reverts back to wild-type rapidly (68% after 6 months of HIV infection). 2014 BMC infectious diseases Discussion HIV M184V 0 5 HIV infections 127 140 25047543 Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe. Second, it is important to note that virological studies showed that the K103N, a major NNRTI mutation, can persist in the absence of treatment. 2014 BMC infectious diseases Discussion HIV K103N 73 78 NNRTI 88 93 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. M36I has been associated with PI exposure, though was not linked to reduced susceptibility in a commercial phenotypic susceptibility system incorporating only patient-derived protease sequences. 2014 The Journal of antimicrobial chemotherapy Discussion HIV M36I 0 4 PR;PI 175;30 183;32 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. The resistance pathway involving M36I could therefore involve the Gag positions in Table S2. 2014 The Journal of antimicrobial chemotherapy Discussion HIV M36I 33 37 Gag 66 69 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. This degree of reduction in PI susceptibility was the same as observed for variant 1403 F6, which contained the V82A major PI resistance mutation, implying clinical relevance in the FCs observed for gag-associated mutations. 2014 The Journal of antimicrobial chemotherapy Discussion HIV V82A 112 116 Gag;PI;PI 199;28;123 202;30;125 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. Use of multiple clones in phenotypic analysis enabled us to test lower-frequency variants and this approach was vindicated by the detection of a protease V82A major mutation in a single clone at virological failure in Patient 1403. 2014 The Journal of antimicrobial chemotherapy Discussion HIV V82A 154 158 PR 145 153 25096075 Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes. We detected a second individual (Patient 3204) with an emergent reduction in PI susceptibility (13-fold to lopinavir), also on a background of reduced susceptibility and associated with amino acid changes in Gag and M36I in protease. 2014 The Journal of antimicrobial chemotherapy Discussion HIV M36I 216 220 PR;Gag;PI 224;208;77 232;211;79 25101529 2014 Update of the drug resistance mutations in HIV-1. A 16th mutation, Y188L, reduces rilpivirine susceptibility 6-fold. 2014 Topics in antiviral medicine Discussion HIV Y188L 17 22 25101529 2014 Update of the drug resistance mutations in HIV-1. Although reverse transcriptase changes associated with the E44D and V118I mutations may have an accessory role in increased resistance to nRTIs in the presence of TAMs, their clinical relevance is very limited. 2014 Topics in antiviral medicine Discussion HIV E44D;V118I 59;68 63;73 RT;NRTI 9;138 30;143 25101529 2014 Update of the drug resistance mutations in HIV-1. As with tenofovir, the K65R mutation may be selected by didanosine, abacavir, or stavudine (particularly in patients with nonsubtype-B clades) and is associated with decreased viral susceptibility to these drugs. 2014 Topics in antiviral medicine Discussion HIV K65R 23 27 25101529 2014 Update of the drug resistance mutations in HIV-1. Cross-resistance studies with raltegravir- and elvitegravir-resistant viruses indicate that Q148H and G140S in combination with mutations L74I/M, E92Q, T97A, E138A/K, G140A, or N155H are associated with 5-fold to 20-fold reduced dolutegravir susceptibility and reduced virologic suppression in patients. 2014 Topics in antiviral medicine Discussion HIV E138A;E138K;E92Q;G140A;G140S;L74I;L74M;N155H;Q148H;T97A 158;158;146;167;102;138;138;177;92;152 165;165;150;172;107;144;144;182;97;156 25101529 2014 Update of the drug resistance mutations in HIV-1. Data are lacking on the potential negative impact of K65R on clinical response to didanosine. 2014 Topics in antiviral medicine Discussion HIV K65R 53 57 25101529 2014 Update of the drug resistance mutations in HIV-1. E138K and to a lesser extent K101E usually occur in combination with the nRTI resistance mutation M184I, which alone does not reduce rilpivirine susceptibility. 2014 Topics in antiviral medicine Discussion HIV K101E;M184I;E138K 29;98;0 34;103;5 NRTI 73 77 25101529 2014 Update of the drug resistance mutations in HIV-1. E92Q alone reduces susceptibility to elvitegravir more than 20-fold and causes limited (<5-fold) cross resistance to raltegravir. 2014 Topics in antiviral medicine Discussion HIV E92Q 0 4 25101529 2014 Update of the drug resistance mutations in HIV-1. Fifteen mutations have been associated with decreased rilpivirine susceptibility (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C, and M230I/L). 2014 Topics in antiviral medicine Discussion HIV E138A;E138G;E138K;E138Q;E138R;F227C;H221Y;K101E;K101P;M230I;M230L;V179L;Y181C;Y181I;Y181V 91;91;91;91;91;131;124;82;82;142;142;106;113;113;113 104;104;104;104;104;136;129;89;89;149;149;111;122;122;122 25101529 2014 Update of the drug resistance mutations in HIV-1. However, for isolates harboring the L100I/ K103N/R/S or V179D as single mutations, no reduction in susceptibility was detected. 2014 Topics in antiviral medicine Discussion HIV K103N;K103R;K103S;L100I;V179D 43;43;43;36;56 52;52;52;41;61 25101529 2014 Update of the drug resistance mutations in HIV-1. However, there is emerging evidence that specific mutations, most notably I47A (and possibly I47V) and V32I, are associated with high-level resistance. 2014 Topics in antiviral medicine Discussion HIV I47A;I47V;V32I 74;93;103 78;97;107 25101529 2014 Update of the drug resistance mutations in HIV-1. In site-directed mutants and clinical isolates, the mutation F121Y has a profound effect on susceptibility to elvitegravir and raltegravir and to a lesser extent to dolutegravir. 2014 Topics in antiviral medicine Discussion HIV F121Y 61 66 25101529 2014 Update of the drug resistance mutations in HIV-1. In some nonsubtype-B HIV-1, D30N is selected less frequently than are other PI mutations. 2014 Topics in antiviral medicine Discussion HIV D30N 28 32 PI 76 78 25101529 2014 Update of the drug resistance mutations in HIV-1. K101E, E138K, and Y181C, each of which reduces rilpivirine susceptibility 2.5-fold to 3-fold, occur commonly in patients receiving rilpivirine. 2014 Topics in antiviral medicine Discussion HIV E138K;Y181C;K101E 7;18;0 12;23;5 25101529 2014 Update of the drug resistance mutations in HIV-1. K101P and Y181I/V reduce rilpivirine susceptibility about 50-fold and 15-fold, respectively, but are uncommonly observed in patients receiving rilpivirine. 2014 Topics in antiviral medicine Discussion HIV Y181I;Y181V;K101P 10;10;0 17;17;5 25101529 2014 Update of the drug resistance mutations in HIV-1. K65E usually occurs in mixtures with wild type. 2014 Topics in antiviral medicine Discussion HIV K65E 0 4 25101529 2014 Update of the drug resistance mutations in HIV-1. K65E/N variants are increasingly reported in patients experiencing treatment failure with tenofovir, stavudine, or didanosine. 2014 Topics in antiviral medicine Discussion HIV K65N;K65E 0;0 6;6 25101529 2014 Update of the drug resistance mutations in HIV-1. K65N gives an approximately 4-fold decrease in susceptibility. 2014 Topics in antiviral medicine Discussion HIV K65N 0 4 25101529 2014 Update of the drug resistance mutations in HIV-1. K65R is selected frequently (4%-11%) in patients with some nonsubtype-B clades for whom stavudine-containing regimens are failing in the absence of tenofovir. 2014 Topics in antiviral medicine Discussion HIV K65R 0 4 25101529 2014 Update of the drug resistance mutations in HIV-1. Minor mutations described in the Q148H/K/R pathway include L74M plus E138A, E138K, or G140S. 2014 Topics in antiviral medicine Discussion HIV E138A;E138K;G140S;L74M;Q148H;Q148K;Q148R 69;76;86;59;33;33;33 74;81;91;63;42;42;42 25101529 2014 Update of the drug resistance mutations in HIV-1. Mutations described in the N155H pathway include this major mutation plus either L74M, E92Q, T97A, E92Q plus T97A, Y143H, G163K/R, V151I, or D232N. 2014 Topics in antiviral medicine Discussion HIV D232N;E92Q;E92Q;G163K;G163R;L74M;N155H;T97A;T97A;V151I;Y143H 141;87;99;122;122;81;27;93;109;131;115 146;91;103;129;129;85;32;97;113;136;120 25101529 2014 Update of the drug resistance mutations in HIV-1. Mutations known to be selected by TAMs (ie, M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E) also confer reduced susceptibility to all currently approved nRTIs. 2014 Topics in antiviral medicine Discussion HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 50;82;82;56;62;44;69;69 54;89;89;60;67;48;76;76 NRTI 152 157 25101529 2014 Update of the drug resistance mutations in HIV-1. N155H mutants tend to predominate early in the course of raltegravir failure, but are gradually replaced by viruses with higher resistance, often bearing mutations G140S+Q148H/R/K, with continuing raltegravir treatment. 2014 Topics in antiviral medicine Discussion HIV G140S;Q148H;Q148K;Q148R;N155H 164;170;170;170;0 169;179;179;179;5 25101529 2014 Update of the drug resistance mutations in HIV-1. Patient-derived viruses with K65E and site-directed mutations replicate very poorly in vitro; as such, no susceptibility testing can be performed. 2014 Topics in antiviral medicine Discussion HIV K65E 29 33 25101529 2014 Update of the drug resistance mutations in HIV-1. Q151M is the most important mutation in the complex (ie, the other mutations in the complex [A62V, V75I, F77L, and F116Y] in isolation may not reflect multidrug resistance). 2014 Topics in antiviral medicine Discussion HIV A62V;F116Y;F77L;V75I;Q151M 93;115;105;99;0 97;120;109;103;5 25101529 2014 Update of the drug resistance mutations in HIV-1. Raltegravir failure is associated with integrase mutations in at least 3 distinct, but not exclusive, genetic pathways defined by 2 or more mutations including (1) a signature (major) mutation at Q148H/K/R, N155H, or Y143R/H/C; and (2) 1 or more additional minor mutations. 2014 Topics in antiviral medicine Discussion HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 207;196;196;196;217;217;217 212;205;205;205;226;226;226 IN 39 48 25101529 2014 Update of the drug resistance mutations in HIV-1. Some nucleoside (or nucleotide) analogue reverse transcriptase inhibitor (nRTI) mutations, like T215Y and H208Y, may lead to viral hypersusceptibility to the nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs), including etravirine, in nRTI-treated individuals. 2014 Topics in antiviral medicine Discussion HIV H208Y;T215Y 106;96 111;101 RT;RT;NNRTI;NRTI;NRTI 41;181;215;74;249 62;202;221;78;253 25101529 2014 Update of the drug resistance mutations in HIV-1. Some of these mutations appear to have a greater effect on susceptibility than others (eg, I50V vs V11I). 2014 Topics in antiviral medicine Discussion HIV I50V;V11I 91;99 95;103 25101529 2014 Update of the drug resistance mutations in HIV-1. T97A results in only a 2-fold change in elvitegravir susceptibility and may require additional mutations for resistance. 2014 Topics in antiviral medicine Discussion HIV T97A 0 4 25101529 2014 Update of the drug resistance mutations in HIV-1. Tenofovir retains activity against the Q151M complex of mutations. 2014 Topics in antiviral medicine Discussion HIV Q151M 39 44 25101529 2014 Update of the drug resistance mutations in HIV-1. The 69 insertion complex consists of a substitution at codon 69 (typically T69S) and an insertion of 2 or more amino acids (S-S, S-A, S-G, or others). 2014 Topics in antiviral medicine Discussion HIV T69S 75 79 25101529 2014 Update of the drug resistance mutations in HIV-1. The addition of L76V to 3 PI resistance-associated mutations substantially increases resistance to lopinavir/ritonavir. 2014 Topics in antiviral medicine Discussion HIV L76V 16 20 PI 26 28 25101529 2014 Update of the drug resistance mutations in HIV-1. The clinical relevance of these connection domain mutations arises mostly in conjunction with thymidine analogue-associated mutations (TAMs) and M184V and have not been associated with increased rates of virologic failure of etravirine or rilpivirine in clinical trials. 2014 Topics in antiviral medicine Discussion HIV M184V 145 150 25101529 2014 Update of the drug resistance mutations in HIV-1. The combinations of reverse transcriptase mutations L100I + K103N/S and L100I + K103R + V179D were strongly associated with reduced susceptibility to rilpivirine. 2014 Topics in antiviral medicine Discussion HIV K103N;K103R;K103S;L100I;L100I;V179D 60;80;60;52;72;88 67;85;67;57;77;93 RT 20 41 25101529 2014 Update of the drug resistance mutations in HIV-1. The M184V mutation alone does not appear to be associated with a reduced virologic response to abacavir in vivo. 2014 Topics in antiviral medicine Discussion HIV M184V 4 9 25101529 2014 Update of the drug resistance mutations in HIV-1. The most common mutational pattern in this pathway is Q148H plus G140S, which also confers the greatest loss of drug susceptibility. 2014 Topics in antiviral medicine Discussion HIV G140S;Q148H 65;54 70;59 25101529 2014 Update of the drug resistance mutations in HIV-1. The negative impact of the protease mutations I47V, I54M, T74P, and I84V and the positive impact of the protease mutation V82A on virologic response to darunavir/ritonavir were shown in 2 data sets independently. 2014 Topics in antiviral medicine Discussion HIV I47V;I54M;I84V;T74P;V82A 46;52;68;58;122 50;56;72;62;126 PR;PR 27;104 35;112 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of 3 of the following mutations:M41L, D67N, L210W, T215Y/F, K219Q/E:is associated with resistance to didanosine. 2014 Topics in antiviral medicine Discussion HIV D67N;K219E;K219Q;L210W;M41L;T215F;T215Y 51;73;73;57;45;64;64 55;80;80;62;49;71;71 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of K103N alone does not affect etravirine response. 2014 Topics in antiviral medicine Discussion HIV K103N 16 21 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of K65R is associated with a reduced virologic response to tenofovir.13 A reduced response also occurs in the presence of 3 or more TAMs inclusive of either M41L or L210W. 2014 Topics in antiviral medicine Discussion HIV K65R;L210W;M41L 16;178;170 20;183;174 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of K70R or M184V alone does not decrease virologic response to didanosine. 2014 Topics in antiviral medicine Discussion HIV K70R;M184V 16;24 20;29 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of M184V appears to delay or prevent emergence of TAMs.30 This effect may be overcome by an accumulation of TAMs or other mutations. 2014 Topics in antiviral medicine Discussion HIV M184V 16 21 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of M46I plus L76V might increase susceptibility to atazanavir when no other related mutations are present. 2014 Topics in antiviral medicine Discussion HIV L76V;M46I 26;16 30;20 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of mutations L24I, I50L/V, F53Y/L/W, I54L, and L76V have been associated with improved virologic response to tipranavir in some studies. 2014 Topics in antiviral medicine Discussion HIV F53L;F53W;F53Y;I50L;I50V;I54L;L24I;L76V 40;40;40;32;32;50;26;60 48;48;48;38;38;54;30;64 25101529 2014 Update of the drug resistance mutations in HIV-1. The presence of TAMs or combined treatment with zidovudine prevents the emergence of K65R in the presence of tenofovir. 2014 Topics in antiviral medicine Discussion HIV K65R 85 89 25101529 2014 Update of the drug resistance mutations in HIV-1. The single mutations L100I*, K101P*, and Y181C*/I*/V* reduce clinical utility. 2014 Topics in antiviral medicine Discussion HIV K101P;L100I;Y181C 29;21;41 34;26;53 25101529 2014 Update of the drug resistance mutations in HIV-1. The T215A/C/D/E/G/H/I/L/N/S/V substitutions are revertant mutations at codon 215 that confer increased risk of virologic failure of zidovudine or stavudine in antiretroviralnaive patients. 2014 Topics in antiviral medicine Discussion HIV T215A;T215C;T215D;T215E;T215G;T215H;T215I;T215L;T215N;T215S;T215V 4;4;4;4;4;4;4;4;4;4;4 29;29;29;29;29;29;29;29;29;29;29 25101529 2014 Update of the drug resistance mutations in HIV-1. The T215Y mutant may emerge quickly from one of these mutations in the presence of zidovudine or stavudine. 2014 Topics in antiviral medicine Discussion HIV T215Y 4 9 25101529 2014 Update of the drug resistance mutations in HIV-1. The Y143R/H/C mutation is uncommon. 2014 Topics in antiviral medicine Discussion HIV Y143C;Y143H;Y143R 4;4;4 13;13;13 25101529 2014 Update of the drug resistance mutations in HIV-1. Their impacts differ, with I50L, I84V, and N88S having the greatest effect. 2014 Topics in antiviral medicine Discussion HIV I50L;I84V;N88S 27;33;43 31;37;47 25101529 2014 Update of the drug resistance mutations in HIV-1. When associated with TAMs, M184V increases abacavir resistance. 2014 Topics in antiviral medicine Discussion HIV M184V 27 32 25101529 2014 Update of the drug resistance mutations in HIV-1. When M184I is combined with E138K or K101E, rilpivirine susceptibility is reduced about 7-fold and 4.5-fold, respectively. 2014 Topics in antiviral medicine Discussion HIV E138K;K101E;M184I 28;37;5 33;42;10 25108107 A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF. Previously, it has been shown that the I10V variant of MDR769 exhibits an unusual "Proline Switch" (PDB ID: 3PJ6) in the 80s loop (Pro79-Val84) as a drug resistance mechanism. 2014 Journal of molecular graphics & modelling Discussion HIV I10V 39 43 25140907 Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. Those with TDR detected by OLA at one or multiple codons (M184V, K103N, Y181C, and G190A) were 10 times more likely to experience virologic failure than those without TDR. 2014 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G190A;K103N;M184V;Y181C 83;65;58;72 88;70;63;77 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. Six patients had Q151M, 24 had >=2 TAMs and 32 had M184V+>=1 TAM. 2014 Journal of the International AIDS Society Discussion HIV M184V;Q151M 51;17 56;22 25141905 HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. This prevalence was higher than the 12.7% reported from a Cambodian study, although it is important to note that multi-NRTI RAMs in that study included Q151M, K65R and 69Ins. 2014 Journal of the International AIDS Society Discussion HIV K65R;Q151M 159;152 163;157 NRTI 119 123 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Although both FNC and 3TC showed high cross-resistance to HIV-1LAI-M184V, FNC still showed strong activity at nontoxic concentration (26.75 nM) whereas 3TC lost the activity (EC50>800 microM) (Table 3). 2014 PloS one Discussion HIV M184V 67 72 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Computer modeling was performed to predict the binding of FNC and 3TC to RT and in turn elucidate the higher level of resistance of M184I and M184V mutants for 3TC than FNC. 2014 PloS one Discussion HIV M184I;M184V 132;142 137;147 RT 73 75 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. FNC showed cross-resistance to it with EC50 of 27.45 nM while 3TC could not inhibit the replication of HIV-1LAI-M184V at concentration up to 800 microM. 2014 PloS one Discussion HIV M184V 112 117 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Four additional amino acid changes (R461K, T468P, D471N and A508T) were also detected in the RNase H domain without obvious correlation (data not shown). 2014 PloS one Discussion HIV R461K 36 41 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. HIV-1LAI-M184V was used as control in this assay since it was a highly 3TC resistant strain. 2014 PloS one Discussion HIV M184V 9 14 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. In addition, we identified another highly frequent mutation of FNC-L214F (from 30.30% at P-5 to 100% at P-21) which was polymorphic in viruses from both treated and untreated patients. 2014 PloS one Discussion HIV L214F 67 72 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. In FNC- induced HIV, mutation frequencies of M184I at P-5 and P11 were 3.03% and 66.67%, respectively, whereas in 3TC- induced HIV,M184I frequency at P-5 was 4.76% and M184I/V frequency of at P-11 was 91.66%. 2014 PloS one Discussion HIV M184I;M184I;M184I;M184V 45;131;168;168 50;136;175;175 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. In order to explore how L214F mutation affects the binding of FNC to RT, we compare the binding modes of three compounds namely FNC, 3TC and DC (Figure 4). 2014 PloS one Discussion HIV L214F 24 29 RT 69 71 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. In present study, no mutation of FNC or 3TC was found at K65R which is probably because of the short induction time. 2014 PloS one Discussion HIV K65R 57 61 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Interestingly, N519S and L214F were found in 3TC-selected strains without obvious resistance correlation. 2014 PloS one Discussion HIV L214F 25 30 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. M184V was found in 3TC- induced viruses except for P-5 (45.83% frequency at P-11, 70.97% frequency at P-16 and 52.17% frequency at P-21). 2014 PloS one Discussion HIV M184V 0 5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. R461K, T468P, D471N and A508T mutations were also detected in the RNase H domain, these mutations may be an adaptation in overall structure, which have synergistic effect in the drug resistance. 2014 PloS one Discussion HIV R461K 0 5 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Since M184I was transient and replaced by M184V in 3TC-resistant patients, this suggests FNC might have different mechanisms for 3TC resistance. 2014 PloS one Discussion HIV M184I;M184V 6;42 11;47 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The dominant mutation site associated with FNC resistance was M184I (from 3.03% at P-5 to 95.83% frequency at P-21) whereas M184V was only detected at P-21 with 2.08% frequency (Table 4). 2014 PloS one Discussion HIV M184I;M184V 62;124 67;129 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The emergence of mutation L214F will result in stronger hydrophobic interaction between residues F214 and F160 which draw F160 away from FNC. 2014 PloS one Discussion HIV L214F 26 31 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The most frequent RT mutations selected by 3TC were M184V and K65R and it will be interesting to determine whether in vitro selection assay also contains the K65R substitution. 2014 PloS one Discussion HIV K65R;K65R;M184V 62;158;52 66;162;57 RT 18 20 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The presence of azido group in FNC leads to stronger steric hindrance in mutant M184I than M184V (Figure 3C and D) whereas the structural interferences were comparable in mutant M184I and M184V for 3TC. 2014 PloS one Discussion HIV M184I;M184I;M184V;M184V 80;178;91;188 85;183;96;193 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. The results of the present study therefore suggest that FNC may be used as a replacement deoxycytidine analogue for 3TC in patients harboring the M184V mutation. 2014 PloS one Discussion HIV M184V 146 151 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. This analysis is explanatory to the fact that the more FNC resistant viruses contain L214F. 2014 PloS one Discussion HIV L214F 85 90 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. This analysis suggests mutant M184I is more resistant to FNC than mutant M184V and explains the higher mutation frequency of M184I than M184V in the FNC-selected HIV-1IIIB strains. 2014 PloS one Discussion HIV M184I;M184I;M184V;M184V 30;125;73;136 35;130;78;141 25144636 Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. This observation is consistent with the results of genotypic resistance analysis in our study, which showed that both mutations M184I and M184V emerged in the HIV-1IIIB strains selected by FNC and 3TC. 2014 PloS one Discussion HIV M184I;M184V 128;138 133;143 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. All naive patients harbored viruses that were resistant to NVP/EFV with a majority of them showing the K103N/S mutation. 2014 PloS one Discussion HIV K103N;K103S 103;103 110;110 25166019 Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. The rates of 181C/I, K103N/S G190A and M184L/V mutations were also higher than in another recent study in Cambodia among patients having a median duration of 12 months up to 4 years on antiretroviral therapy. 2014 PloS one Discussion HIV G190A;K103N;K103S;M184L;M184V 29;21;21;39;39 34;28;28;46;46 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. In contrast, in the case of Indian HIV-1C isolates, not only does the absence of a dicysteine motif due to nearly universal C31S polymorphism in India reduce the potential for brain infiltration, but the absence of neurotoxicity due to gp120 may also contribute to reduced neurovirulence. 2014 PloS one Discussion HIV C31S 124 128 gp120 236 241 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. In the case of Southern African isolates with a C31S substitution in Tat, in spite of the presence of a neurotoxic gp120, the likelihood that it would appear in the brain would be significantly reduced. 2014 PloS one Discussion HIV C31S 48 52 gp120;Tat 115;69 120;72 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. The premise of those studies has been that the decreased monocyte migration caused by C31S polymorphism in Tat prevents infiltration of HIV-infected monocytic phagocytes into brain which forestalls additional events that cause inflammatory insult due to viral proteins and host cytokines in the CNS. 2014 PloS one Discussion HIV C31S 86 90 Tat 107 110 HIV infections 136 148 25188269 The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates. Therefore, until now, the decreased neurovirulence of HIV-1C has been primarily attributed to C31S polymorphism. 2014 PloS one Discussion HIV C31S 94 98 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. 1 could better fill the hydrophobic cavity created by Tyr181 to Cys181 change, thus improving potency against the mutant strain. 2015 Biochimica et biophysica acta Discussion HIV Y181C 54 70 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. FEP simulations using the Desmond MD code have been evaluated in a retrospective study of the binding of benzyloxazole inhibitors to both wild-type and the Y181C variant of the well-studied drug target HIV-RT. 2015 Biochimica et biophysica acta Discussion HIV Y181C 156 161 RT 206 208 25196360 Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design. For example, relative free energies of -4.40 and -1.75 kcal/mol are reported for i-Pr binding to the Y181C mutant, using MCPRO and Desmond, respectively. 2015 Biochimica et biophysica acta Discussion HIV Y181C 101 106 PR 83 85 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. By showing that instead of targeting EFV binding affinity K103N may target the p51-p66 salt bridge in modulating the conformational dynamics of EFV-bound RT, in turn reducing enzyme sliding on the T/P substrate and permitting polymerization, our data highlight a potential critical role for this salt bridge in the global dynamics and subsequent function of RT. 2014 Nucleic acids research Discussion HIV K103N 58 63 RT;RT 154;358 156;360 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Consistent with this, we observed no reduction of EFV binding affinity in the K103N mutant. 2014 Nucleic acids research Discussion HIV K103N 78 83 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Furthermore, our findings challenge the current convention that drug resistance correlates with reduced drug binding affinity and shed light on a previously described anomaly: direct contacts between EFV and K103N are not observed, and a stereochemical basis for any effect on binding cannot be inferred from the crystal structures of WT or K103N RT in complex with EFV. 2014 Nucleic acids research Discussion HIV K103N;K103N 208;341 213;346 RT 347 349 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. In contrast, K103N did lower the binding affinity of NVP for the RT-T/P complex, demonstrating that a single mutation in RT can elicit different modes of resistance to structurally diverse NNRTIs. 2014 Nucleic acids research Discussion HIV K103N 13 18 NNRTI;RT;RT 189;65;121 195;67;123 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. In the crystal structure of K103N RT in complex with RPV, the salt bridge between K101 and E138 remains intact, and our anisotropy assays show that RPV binds with increased affinity to the RT-T/P complex (Supplementary Figure S2). 2014 Nucleic acids research Discussion HIV K103N 28 33 RT;RT 34;189 36;191 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Notably, the putative mechanism by which the K103N variant resists EFV inhibition (see for a review; see also Supplementary Discussion) has thus far been based on experiments conducted in the absence of T/P or dNTP or both. 2014 Nucleic acids research Discussion HIV K103N 45 50 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Of note, RPV retains activity against HIV-1 containing K103N. 2014 Nucleic acids research Discussion HIV K103N 55 60 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Our anisotropy and PIFE data both show the consequence of the mutant's disruption of the EFV-induced conformational change: EFV-bound K103N retains its fingers/thumb grip on the T/P when dNTP is present and thus may stably reside in the functional polymerase-competent mode rather than slide unproductively along the T/P. 2014 Nucleic acids research Discussion HIV K103N 134 139 Pol 248 258 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Our intra-molecular spFRET studies demonstrate that the binding of EFV increases opening of the fingers and thumb in WT but not in K103N RT-T/P-dNTP complexes. 2014 Nucleic acids research Discussion HIV K103N 131 136 RT 137 139 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We discovered a critical role for dNTP in the mechanism of EFV resistance in that inhibitor-bound K103N RT retained its grip on the T/P and reduced sliding only in the presence of dNTP. 2014 Nucleic acids research Discussion HIV K103N 98 103 RT 104 106 25232099 Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. We further demonstrate (v) that each of these effects can be enhanced by the formation of a salt bridge between E138 (p51) and K101 (p66) and (vi) that the clinical NNRTI resistance mutation K103N restores the polymerase-competent intra- and inter-molecular RT dynamics, potentially by eliminating the salt bridge between K101 and E138. 2014 Nucleic acids research Discussion HIV K103N 191 196 Pol;NNRTI;RT 210;165;258 220;170;260 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. This conclusion is supported by the fact that M184V-containing virus for which viral replication capacity is also diminished compared to WT also sustained similar levels of cell-to-cell transmission as well as establishment of and reactivation from latency. 2014 Viruses Discussion HIV M184V 46 51 25243372 Fitness impaired drug resistant HIV-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency. We have hypothesized that the R263K mutation in HIV integrase may contribute to the prevention of virological failure in patients who are treated with DTG in combination with other ARVs. 2014 Viruses Discussion HIV R263K 30 35 IN 52 61 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. A second difference between subtype AFSU strains and other subtypes is the high proportion of antiretroviral-naive patients with the NRTI-resistance mutation A62V. 2014 AIDS (London, England) Discussion HIV A62V 158 162 NRTI 133 137 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. Although A62V alone does not reduce NRTI susceptibility, it is an accessory utation that frequently co-occurs with K65R and Q151M, mutations responsible for multi-NRTI resistance. 2014 AIDS (London, England) Discussion HIV A62V;K65R;Q151M 9;115;124 13;119;129 NRTI;NRTI 36;163 40;167 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. Although G190S does not directly reduce etravirine or rilpivirine susceptibility, it has a weight of 1.5 in the Tibotec (Jansenn Therapeutics, Raritan, New Jersey, USA) etravirine genotypic susceptibility score making it one of the main etravirine-resistance mutations. 2014 AIDS (London, England) Discussion HIV G190S 9 14 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. By a different mechanism, subtype C viruses are predisposed to developing the NRTI-resistance mutation K65R. 2014 AIDS (London, England) Discussion HIV K65R 103 107 NRTI 78 82 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. By the same mechanism, the NRTI-resistance mutation V75M is more common in CRF01_AE; and the protease inhibitor-resistance mutation V82M is more common in subtype G. 2014 AIDS (London, England) Discussion HIV V75M;V82M 52;132 56;136 PR;NRTI 93;27 101;31 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S also causes higher levels of resistance than most NNRTI-resistance mutations. 2014 AIDS (London, England) Discussion HIV G190S 0 5 NNRTI 56 61 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. G190S was not identified in subtype A viruses in the Stanford HIVDB from more than 700 antiretrovial-naive patients from Russia and other FSU countries. 2014 AIDS (London, England) Discussion HIV G190S 0 5 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. have described a large transmission cluster of viruses in Quebec with G190A, which like G190S is a conservative amino acid substitution suggesting that viruses with G190S may also be transmissible. 2014 AIDS (London, England) Discussion HIV G190A;G190S;G190S 70;88;165 75;93;170 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. It is not known whether the high prevalence of A62V combined with the predisposition to G190S reduces the genetic barrier to resistance of subtype AFSU strains to NRTI/NNRTI-containing regimens. 2014 AIDS (London, England) Discussion HIV A62V;G190S 47;88 51;93 NNRTI;NRTI 168;163 173;167 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. Nonetheless, the predisposition of subtype AFSU to developing G190S demonstrates the need for characterizing genetic mechanisms of resistance in diverse populations of HIV-1-infected patients. 2014 AIDS (London, England) Discussion HIV G190S 62 67 HIV infections 168 182 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The fact that G190S was the most common NNRTI-resistance mutation in subtype AFSU strains is notable because globally G190S is not among the most common NNRTI-resistance mutations in NNRTI-experienced patients. 2014 AIDS (London, England) Discussion HIV G190S;G190S 14;118 19;123 NNRTI;NNRTI;NNRTI 40;153;183 45;158;188 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The median reduction in NNRTI susceptibility by the PhenoSense assay (Monogram Bioscience, South San Francisco, California, USA) for 14 viruses with G190S and no other major NNRTI-resistance mutation was more than 200-fold for nevirapine and 130-fold for efavirenz compared with 50-fold and 20-fold, respectively, for viruses with K103N alone (http://hivdb.stanford.edu/pages/phenoSummary/Pheno.NNRTI.Simple.html). 2014 AIDS (London, England) Discussion HIV G190S;K103N 149;331 154;336 NNRTI;NNRTI;NNRTI 24;174;395 29;179;400 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The NNRTI-resistance mutation V106M is more common in subtype C viruses because it requires one nucleotide change compared with two changes in other subtypes. 2014 AIDS (London, England) Discussion HIV V106M 30 35 NNRTI 4 9 25259833 A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses. The relative ease with which G190S occurs in Russian subtype A strains also suggests the need for retrospective and/or prospective studies to verify that standard NRTI/NNRTI first-line regimens are as efficacious in treating subtype AFSU viruses as they are in treating viruses belonging to other subtypes. 2014 AIDS (London, England) Discussion HIV G190S 29 34 NNRTI;NRTI 168;163 173;167 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. A recent study revealed that the S40F mutation can occur naturally under anti-retroviral treatment, and even more, appears to correlate with high viral load, low CD4+ cell counts, and ultimate treatment failure. 2014 Viruses Discussion HIV S40F 33 37 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Although the steady state amount of S40F mutant Gag was not affected, the MHC-I antigen presentation, as the final consequence of proteasomal degradation, was significantly enhanced. 2014 Viruses Discussion HIV S40F 36 40 Gag 48 51 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Furthermore, the S40F mutation induces Gag-containing filopodia-like membrane protrusions which were speculated to trigger cell to cell transmission of HIV-1 under antiviral treatment. 2014 Viruses Discussion HIV S40F 17 21 Gag 39 42 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Hence, it is unlikely that the increased ubiquitination of HIV-Gag observed for the S40F mutant could be consequent to any potential misfolding within that domain of p6. 2014 Viruses Discussion HIV S40F 84 88 Gag;Gag 63;166 66;168 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. However, while in the context of the S40F mutation, p6 likely contributes to membrane binding, this effect may not occur in the context of wt Gag as in the absence of S40F the size of the hydrophobic patch might be too small to be able to contribute to membrane association. 2014 Viruses Discussion HIV S40F;S40F 37;167 41;171 Gag;Gag 142;52 145;54 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In addition, the specific CA-SP1 processing defect of the S40F mutant could also be caused by Gag ubiquitination as particularly the CA-SP1 junction (359KARVL AEAM) is the only cleavage site within Gag that has a lysine in close proximity. 2014 Viruses Discussion HIV S40F 58 62 SP1;SP1;Gag;Gag;Capsid;Capsid 29;136;94;198;26;133 32;139;97;201;28;135 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In correlation with an enhanced MHC-I antigen presentation of Gag-derived epitopes, the S40F mutant displayed an increased capacity to activate T cells in vitro. 2014 Viruses Discussion HIV S40F 88 92 Gag 62 65 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. In the present study we characterize a potential membrane interacting domain, at least for the natural occurring p6 mutant S40F, which is induced by the formation of a hydrophobic patch involving Phe-40 and Tyr-36 within the C-terminal alpha-helix of p6. 2014 Viruses Discussion HIV S40F 123 127 Gag;Gag 113;251 115;253 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. It would be intriguing to investigate the contribution of the S40F mutation to this process. 2014 Viruses Discussion HIV S40F 62 66 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Moreover, in the case of the S40F mutant Gag ubiquitination does not correlate with virus release and occurs independently of l-domain function. 2014 Viruses Discussion HIV S40F 29 33 Gag 41 44 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Moreover, polyubiquitinated Gag that is incorporated into virions might account for the defects in CA-SP1 processing, virus morphogenesis, and infectivity observed for the S40F mutant. 2014 Viruses Discussion HIV S40F 172 176 SP1;Gag;Capsid 102;28;99 105;31;101 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Nevertheless, an increased membrane association of Gag could at least provide one explanation for the augmented K48-linked polyubiquitination observed for the S40F mutant. 2014 Viruses Discussion HIV S40F 159 163 Gag 51 54 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Nevertheless, the budding competent S40F mutant, like the release defective PTAP mutant, exhibits K48-linked polyubiquitination, a type of polyubiquitin chain that was never implicated in any ESCRT function. 2014 Viruses Discussion HIV S40F 36 40 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. One possible explanation for the proteasomal degradation of S40F mutant Gag would be misfolding induced by this non-conservative amino acid exchange. 2014 Viruses Discussion HIV S40F 60 64 Gag 72 75 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Taken together, we could demonstrate that the S40F mutation leads to the formation of a hydrophobic patch which increases the membrane binding of Gag and thus triggers its polyubiquitination, most likely by membrane resident ubiquitin ligases. 2014 Viruses Discussion HIV S40F 46 50 Gag 146 149 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The membrane interaction of p6 is specifically enhanced when Ser-40 is exchanged to Phe which can be rationalized from the NMR structure of p6 showing that the residue at position 40 is in spatial proximity to the bulky hydrophobic residue Tyr-36 (Figure 9). 2014 Viruses Discussion HIV S40F 61 87 Gag;Gag 28;140 30;142 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. The residue at position 40 is relatively close in space to Tyr-36, which then creates the new hydrophobic domain as the driving force that augments membrane interaction observed selectively for the S40F mutant. 2014 Viruses Discussion HIV S40F 198 202 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. This notion is further supported by the finding that overexpression of ALIX has no influence on Gag ubiquitination or virus release of the S40F mutant although it significantly enhances virus release of both the PTAP mutant and the S40F/ PTAP double mutant. 2014 Viruses Discussion HIV S40F;S40F 139;233 143;237 Gag 96 99 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. This notion is further supported by the observation that the S40F and PTAP mutants display a defective Gag processing as well as enhanced levels of Gag ubiquitination, whereas the mutation of Ser-40 to Ala or Asn does neither affect Gag ubiquitination nor Gag processing. 2014 Viruses Discussion HIV S40F 61 65 Gag;Gag;Gag;Gag 104;149;234;257 107;152;237;260 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. This result implicates that S40F mutant Gag might have the potential to elicit a more potent activation of cytotoxic T-cells in vivo. 2014 Viruses Discussion HIV S40F 28 32 Gag 40 43 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. Thus, it is legitimate to assume that this increase in membrane bound Gag observed for the S40F mutant occurs independently of virus release. 2014 Viruses Discussion HIV S40F 91 95 Gag 70 73 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. We could neither detect an accumulation of budding virions on the cell surface nor a delay in virus release kinetics in our previous studies for the S40F mutant, which was then confirmed by Watanabe et al. 2014 Viruses Discussion HIV S40F 149 153 25279819 Mutation of the highly conserved Ser-40 of the HIV-1 p6 gag protein to Phe causes the formation of a hydrophobic patch, enhances membrane association, and polyubiquitination of Gag. When the polar residue Ser-40 is substituted with either Asn or Asp, as exemplified by the mutants S40N and S40D, it is replaced with another polar, or even a negatively charged residue at this position. 2014 Viruses Discussion HIV S40D;S40N 108;99 112;103 Asp 64 67 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Although IL2 can stimulate T cell growth and promote T cell line replication, an unexpected effect of IL2 in regard to G367R reversion was a differential result in varying cell types. 2014 Virology journal Discussion HIV G367R 119 124 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. APOBEC-negative, showed that the G367R virus was able to revert in SupT1 but not in MT4 cells. 2014 Virology journal Discussion HIV G367R 33 38 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Cell-type differences may also explain why G367R can spread between some cell types, e.g., MT2 and SupT1, but not others. 2014 Virology journal Discussion HIV G367R 43 48 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Differences in sensitivity of G367R virus to entry inhibitors varied by 10-10,000-fold between cell-to-cell transmission and cell-free transmission. 2014 Virology journal Discussion HIV G367R 30 35 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. G367R, like D368R, changes the local structure around the CD4bs of env, rendering the virus in cell-free form unable to bind CD4. 2014 Virology journal Discussion HIV D368R;G367R 12;0 17;5 Env 67 70 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Indeed, the Env G367R virus seems to be able to cause infection only as cell-associated virus. 2014 Virology journal Discussion HIV G367R 16 21 Env 12 15 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Interestingly, MT2 and MT4 cells are both highly sensitive to WT HIV in cell-free infection but behave quite differently in regard to susceptibility to the env mutant G367R in cell-associated entry. 2014 Virology journal Discussion HIV G367R 167 172 Env 156 159 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. It is important to note that our study was focused on the G367R mutation in Env and relevant reversion at this site. 2014 Virology journal Discussion HIV G367R 58 63 Env 76 79 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. MT4 cells are highly sensitive to cell-free WT HIV but do not support cell-associated G367R reversion. 2014 Virology journal Discussion HIV G367R 86 91 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Our finding that a G367R reversion is cell type dependent supports the idea that viral involvement in cell-associated or cell-free transmission depends both on the virus and target cell. 2014 Virology journal Discussion HIV G367R 19 24 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Our findings represent an example of a situation whereby some env mutants such as G367R may be defective in regard to receptor binding but that this can be overcome by cellular mechanisms that compensate and promote cell-associated defective virus to slowly replicate, such that the latter can revert. 2014 Virology journal Discussion HIV G367R 82 87 Env 62 65 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Previous studies showed that the CD4bs mutation D368R within env lost affinity for neutralizing antibodies and that the mutated viruses were also defective as tested in cell-free infections. 2014 Virology journal Discussion HIV D368R 48 53 Env 61 64 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Protein kinase C (PKC) may be involved in the reversion of G367R because the PKC modulator PMA and the Ca++ ionophore ionomycin both inhibited G367R reversion in both MT2 and SupT1 cells (Figure 6b). 2014 Virology journal Discussion HIV G367R;G367R 59;143 64;148 Capsid 103 105 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. Similar to what has been observed with the G367R mutant, the blocking activity of CD4bs specific antibodies largely compromises free virus but blocking activity is much less in cell-cell transmission, thus allowing virus entry, replication and spread to occur. 2014 Virology journal Discussion HIV G367R 43 48 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The cellular mechanisms underlying the rescue of G367R are complex. 2014 Virology journal Discussion HIV G367R 49 54 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The fact that the gp120 binding inhibitor DS003 and the CXCR4 inhibitor AMD3100 can inhibit G367R spread and that the virus can revert in TZM-bl cells but not in 293 T cells indicates that cell-associated transmission of G367R is a receptor-related event. 2014 Virology journal Discussion HIV G367R;G367R 92;221 97;226 gp120 18 23 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. The G367R mutant is suggestive of conformational changes in the env protein but the process of escape is not fully understood. 2014 Virology journal Discussion HIV G367R 4 9 Env 64 67 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. This may explain why the G367R or D368R mutations have never been observed as cell-free forms in infected individuals or in tissue culture. 2014 Virology journal Discussion HIV D368R;G367R 34;25 39;30 25287969 Identification of an env-defective HIV-1 mutant capable of spontaneous reversion to a wild-type phenotype in certain T-cell lines. This suggests that an APOBEC-independent mechanism may be involved and that different mechanisms of G367R reversion may be presenting MT2 vs SupT1 cells (Figure 6a). 2014 Virology journal Discussion HIV G367R 100 105 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. , who studied a subtype B HIV variant harboring K103N related to a cluster of 29 virus sequences. 2014 PloS one Discussion HIV K103N 48 53 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. In TN individuals, M41L (2.1%), M184I/V (2.6%), K103N/S (3.65%) and G190A/S (3.67%) were the most common mutations detected. 2014 PloS one Discussion HIV G190A;G190S;K103N;K103S;M184I;M184V;M41L 68;68;48;48;32;32;19 75;75;55;55;39;39;23 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Mutations such as K103N, which do not impact significantly on viral fitness, can persist in the absence of drug pressure and interfere with NNRTI-based treatment effectiveness. 2014 PloS one Discussion HIV K103N 18 23 NNRTI 140 145 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Our results show that since 2004, the frequency of K103N/S increased from 1.5% before 2003 to 4.1% in 2011 while G190A/S frequency decreased from 5.6% to 3.1%. 2014 PloS one Discussion HIV G190A;G190S;K103N;K103S 113;113;51;51 120;120;58;58 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. Recent studies have described a lower frequency of M184 V mutations in patients with VL>100,000 copies/ml treated with emtricitabine/tenofovir compared to patients treated with lamivudine/tenofovir. 2014 PloS one Discussion HIV M184V 51 57 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. The frequency of the most common NRTI-associated resistance mutations, M184 V/I, decreased by 20% in 2011 as compared to the 2001-2003 period. 2014 PloS one Discussion HIV M184I;M184V 71;71 79;79 NRTI 33 37 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. This change in NNRTI mutation trends suggests that the profile of Quebec's primary/recent HIV infected population may have evolved towards favoring K103N variants as recently shown by Ruelle et al. 2014 PloS one Discussion HIV K103N 148 153 NNRTI 15 20 HIV infections 90 102 25295725 A significant reduction in the frequency of HIV-1 drug resistance in Quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. We previously described a transmission chain of G190A-containing infections among primary/recently HIV-infected individuals, between 2001 and 2007. 2014 PloS one Discussion HIV G190A 48 53 HIV infections 99 111 25314293 Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase. To simplify the development, we chose clade B virus and focused on the following mutations in the RT region: M41L, K65R, K70R, K103N, M184V and T215Y/F. 2014 PloS one Discussion HIV K103N;K65R;K70R;M184V;M41L;T215F;T215Y 127;115;121;134;109;144;144 132;119;125;139;113;151;151 RT 98 100 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Mixing experiments of mutants in the background of wild type showed a conservative accuracy of 0.1% for K103N and 0.25% for Y181C with a high reproducibility. 2014 PloS one Discussion HIV K103N;Y181C 104;124 109;129 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The relatively low prevalence of Y181C in our study (6.5%) is at the same level as in the Swiss study and no major impact on the therapy outcome would be expected if our patients had been given NNRTI-containing therapy The prevalence of drug-resistant minor HIV-1 variants in Ethiopia has not been previously investigated. 2014 PloS one Discussion HIV Y181C 33 38 NNRTI 194 199 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. The Y181C mutation was found in six of the 92 (6.5%) Ethiopians living in Addis Ababa with mutant frequencies ranging from 0.25% to 4.5%. 2014 PloS one Discussion HIV Y181C 4 9 25333961 Minority drug-resistant HIV-1 variants in treatment naive East-African and Caucasian patients detected by allele-specific real-time PCR. Therefore, to gain further knowledge of to which extent direct sequencing underestimates the presence of TDR in African populations, we analysed Ethiopians infected with HIV-1C living in Addis Ababa, and East Africans with HIV-1C living in Sweden and compared the results with that of Caucasians with HIV-1B living in Stockholm, for the presence of the major NNRTI mutations, K103N and Y181C. 2014 PloS one Discussion HIV K103N;Y181C 376;386 381;391 NNRTI 359 364 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. For the DRV-PR1 and DRV-PR2 complexes, the mutations V32I, I47V, V32'I and I47'V in PR2 not only weaken their van der Waals interactions with DRV relative to PR1, but also induce the decrease in the van der Waals interactions of I50 and D29' in PR2 with DRV. 2014 Scientific reports Discussion HIV I47V;V32I 59;53 63;57 PR;PR;PR;PR;PR 24;84;245;12;158 27;87;248;15;161 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. Similarly, in the case of the APV-PR1 and APV-PR2 complexes, the mutations I47V, V32'I and V82'I in PR2 result in the decrease of their van der Walls interactions with APV compared to PR1, moreover induce the reduction in the van der Waals interactions of the residues I50, P81, I83, G27' and P81' in PR2 with APV. 2014 Scientific reports Discussion HIV I47V 75 79 PR;PR;PR;PR;PR 46;100;301;34;184 49;103;304;37;187 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. Structurally, the mutations V32I and V82I increase the size of these two residues, and the mutation I47V decrease that of this mutated residue. 2014 Scientific reports Discussion HIV I47V;V32I;V82I 100;28;37 104;32;41 25362963 Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations. The previous studies suggest that the wild-type PR2 sequence harbors multiple substitutions such as V32I, I47V and V82I. 2014 Scientific reports Discussion HIV I47V;V32I;V82I 106;100;115 110;104;119 PR 48 51 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. A similar conclusion regarding the neurological impact of the C31S substitution in patients with clade C HIV can be drawn from neuroimaging studies. 2014 Journal of neurovirology Discussion HIV C31S 62 66 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Results from the present study are consistent with the outcomes of studies revealing substantial cognitive impairment in patients residing in India, where the C31S substitution is reportedly dominant, and also South Africa, where the C31S substitution is present but with reduced frequency. 2014 Journal of neurovirology Discussion HIV C31S;C31S 159;234 163;238 25366660 Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. Results from the present study suggest that the C31S substitution does not confer decreased risk of cognitive impairment among seropositive individuals. 2014 Journal of neurovirology Discussion HIV C31S 48 52 25371739 Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia. The results of the present study revealed that the most common point mutations, which result in Thr55Ala and Pro57Ser amino acid substitutions, were not detected in the P. 2014 Experimental and therapeutic medicine Discussion HIV P57S;T55A 109;96 117;104 25371739 Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia. With the absence of common mutations, two other nonsynonymous point mutations, Asp90Asn and Glu98Lys, were identified in the P. 2014 Experimental and therapeutic medicine Discussion HIV D90N;E98K 79;92 87;100 Asp 79 82 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Although we previously described the selection of a second-site HIV-1 IN mutation (T125A) that restored function to replication-defective P109S mutant virus, the T125A change on its own conferred no obvious growth disadvantage. 2014 Molecular therapy. Methods & clinical development Discussion HIV P109S;T125A;T125A 138;83;162 143;88;167 IN 70 72 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. As numerous changes in alpha4/5 connector residues affect the HIV-1 IN-LEDGF/p75 interaction, we speculate that altered connector loop position could determine the influence of the K42E mutation on the virus-host interaction. 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E 181 185 IN 68 70 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Because our data emphasizes the benefit of the K42E mutation in the backdrop of reverse-charge substitutions at multiple other LEDGF/p75 and IN positions, additional structural work with K42E IN mutant proteins will be required to fully appreciate the molecular basis of the integration gain-of-function phenotype. 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E;K42E 47;187 51;191 IN;IN 141;192 143;194 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. It, therefore, seems possible that the K42E mutation could influence the protein interaction through altering the Asp167-Lys360 contact. 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E 39 43 Asp 114 117 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Strikingly, the K42E mutation by itself reduced HIV-1 titer ~7- to 10-fold (Figures 4c and 6a), which is primarily attributable to a reverse transcription defect (Figure 6b). 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E 16 20 RT 133 154 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The importance of the K42E gain-of-function mutation is evident by its independent selection through the serial passage of defective IN mutant viruses RR and KR in LEDGF/p75 EEE-expressing cells (Figures 3 and 4). 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E 22 26 IN 133 135 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The inability for EEE LEDGF/p75 to support K42E IN strand transfer activity in vitro (Figure 5) likely accounts for the added K42E IN mutant viral defect in EEE-expressing cells. 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E;K42E 43;126 47;130 IN;IN 48;131 50;133 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The K42E mutation impressively boosted the level of RR IN mutant reverse transcription, from ~20 to ~70% of the WT, even though the change on its own conferred an approximately fivefold reverse transcription defect (Figure 6b). 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E 4 8 RT;RT;IN 65;186;55 86;207;57 25383358 Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. The K42E mutation to the best of our knowledge is the first example of an HIV-1 IN gain-of-function mutation that by itself severely limits virus activity, though we do note the description of pleiotropic gain-of-function mutations in other biological systems. 2014 Molecular therapy. Methods & clinical development Discussion HIV K42E 4 8 IN 80 82 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Accordingly, the H171T IN change minimally affects the IN-LEDGF/p75 binding. 2014 Retrovirology Discussion HIV H171T 17 22 IN;IN 23;55 25;57 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Consequently, bound BI-1001 failed to induce aberrant multimerization of recombinant A128T IN and accordingly HIV-1NL4-3 containing the A128T IN substitution exhibited marked resistance to BI-1001. 2014 Retrovirology Discussion HIV A128T;A128T 85;136 90;141 IN;IN 91;142 93;144 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. HIV-1 seems to exploit these structural differences between BI-D and LEDGF/p75 interactions with IN during the process of evolution of the H171T IN escape mutation. 2014 Retrovirology Discussion HIV H171T 139 144 IN;IN 97;145 99;147 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. In contrast with the significant reduction in BI-D binding affinity, the H171T IN substitution only minimally reduced LEDGF/p75 binding affinity to recombinant H171T IN. 2014 Retrovirology Discussion HIV H171T;H171T 73;160 78;165 IN;IN 79;166 81;168 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. In contrast, the H171T IN substitution was able to resist BI-D through decreasing the ability of the inhibitor to bind IN. 2014 Retrovirology Discussion HIV H171T 17 22 IN;IN 23;119 25;121 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. In infected cells, where endogenous LEDGF/p75 levels significantly exceed what is needed for HIV-1 integration, HIV-1NL4-3 with the H171T substitution was not compromised for HIV-1 replication. 2014 Retrovirology Discussion HIV H171T 132 137 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Significantly, this level of resistance in infected cells correlates closely with ~84-fold reduced binding affinity of the inhibitor to recombinant H171T IN CCD as compared with its WT counterpart. 2014 Retrovirology Discussion HIV H171T 148 153 IN 154 156 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The A128T IN substitution does not significantly reduce BI-1001 binding to HIV-1 IN CCD with all hydrogen bonding and electrostatic interactions of BI-1001 with HIV-1 IN being fully preserved in WT and A128T INs. 2014 Retrovirology Discussion HIV A128T;A128T 4;202 9;207 IN;IN;IN;IN 10;81;167;208 12;83;169;211 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The mechanism for H171T IN resistance is distinct from the previously described mechanism of resistance for the A128T IN escape mutation under the selective pressure of related, archetypal inhibitor BI-1001. 2014 Retrovirology Discussion HIV A128T;H171T 112;18 117;23 IN;IN 24;118 26;120 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. The Ndelta protonated His171 hydrogen bonds the tert-butoxy ether oxygen of BI-D, which is compromised upon the H171T IN substitution. 2014 Retrovirology Discussion HIV H171T 112 117 IN 118 120 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. These interactions are compromised by the H171T substitution, with the Thr171 side chain forming a less electrostatically favorable hydrogen bond with the BI-D carboxylic acid and lacking any additional interactions with the tert-butoxy ether oxygen (Figure 5). 2014 Retrovirology Discussion HIV H171T 42 47 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. We show that HIV-1NL4-3 containing the H171T IN substitution confers ~68-fold resistance to BI-D. 2014 Retrovirology Discussion HIV H171T 39 44 IN 45 47 25421939 The mechanism of H171T resistance reveals the importance of Ndelta-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Yet, genotyping of HIV-1NL4-3 variants under increasing selective pressure of ALLINI BI-D has revealed the H171T IN substitution as a key amino acid substitution. 2014 Retrovirology Discussion HIV H171T 107 112 IN 113 115 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Alternatively, HIV vectors with mutation D64V or N will be chosen for the situation where vectors with a nonintegrating phenotype are required. 2014 Molecular therapy. Nucleic acids Discussion HIV D64V 41 45 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Although D167H substitution of IN represents a net gain of function for HIV vector integration, it is very unusual in HIV, because it probably affects particles release in a complete viral cycle as showed in viruses carrying IN D167A or K substitutions. 2014 Molecular therapy. Nucleic acids Discussion HIV D167A;D167H 228;9 233;14 IN;IN 31;225 33;227 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. D167H mutation most likely keeps IN catalytic activity unchanged, but rather affects PIC structural features modifying its interaction with a nuclear protein, increasing its stability, its anchoring to chromatin, and consequently integration of the linear vector genome at later time points. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H 0 5 IN 33 35 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Finally, analysis of LTR borders revealed twice more deletions for the N vector than for LQ and D64V vectors. 2014 Molecular therapy. Nucleic acids Discussion HIV D64V 96 100 LTR 21 24 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. For instance, D64V IN, a pure catalytically silent enzyme, induced the least integrative phenotype of all NILV, suggesting that vectors with class II mutations, Q168A, N, or LQ, retain some IN activity, which is concordant with previous in vitro studies that analyzed some of the mutations used here (Table 1). 2014 Molecular therapy. Nucleic acids Discussion HIV D64V;Q168A 14;161 18;166 IN;IN 19;190 21;192 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. HIV vectors with IN D167H substitution will be preferred in strategies requiring transgene integration in fast dividing cells, as well as to transduce primary cells with low permeability to LV such as CD34+ hematopoietic stem cells. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H 20 25 IN 17 19 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. However, in our study, IN K264H conservative replacement possibly retains some catalytic activity. 2014 Molecular therapy. Nucleic acids Discussion HIV K264H 26 31 IN 23 25 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. In fact, this mutation affects later time points of our analysis with vector D167H still integrating between 48 and 72 hours following transduction. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H 77 82 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. In vitro, catalytic activity of a IN with nonconservative substitutions RRK 262-264 DVE was abolished with substitution K264E having the deeper impact on enzyme activity. 2014 Molecular therapy. Nucleic acids Discussion HIV K264E 120 125 IN 34 36 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Indeed, in our experiments, vector D167H seem to function as D167A mutant with no impact on early events of transduction as RT (Figure 6d). 2014 Molecular therapy. Nucleic acids Discussion HIV D167A;D167H 61;35 66;40 RT 124 126 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Integrase mutations D167A and D167K induced opposite effect on single round infectivity of HIV with D167A increasing it to 140% while D167K reduced it to 5% of WT indicating a critical role played by this residue in the processing of the PIC. 2014 Molecular therapy. Nucleic acids Discussion HIV D167A;D167A;D167K;D167K 20;100;30;134 25;105;35;139 IN 0 9 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Interestingly though, IN mutant D167H outperformed WT vector for transduction efficiency and integration. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H 32 37 IN 22 24 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. It thus appears that the pattern of integration of Q168A vector is largely mediated by a remaining ability to interact with these cellular factors in vivo. 2014 Molecular therapy. Nucleic acids Discussion HIV Q168A 51 56 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Moreover, as an equivalent decrease in the linear forms of vector D167H and WT between 48 and 72 hours after transduction (Figure 6g) led on one hand to a continuing integration of the former but not of the latter also supports the view of an increased stability of a PIC carrying a D167H IN. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H;D167H 66;283 71;288 IN 289 291 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Most notably, vectors D64V, N, and D167H are of greater interest in gene transfer applications. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H;D64V 35;22 40;26 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Of all vectors analyzed here, the one carrying the D167H IN displayed the most intriguing phenotype with an increased integration rate of about 40% as compared with WT vectors (Table 2). 2014 Molecular therapy. Nucleic acids Discussion HIV D167H 51 56 IN 57 59 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Regarding chromosomal distribution across the genome, WT, D167H, and Q168A vectors were quite indistinguishable, while vectors D64V, LQ, and N displayed a wide degree of variation. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H;D64V;Q168A 58;127;69 63;131;74 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The fact that D167A or K substitutions do not reduce IN enzymatic activity, but slightly affect RT and interaction with p75/LEDGF, points to a change in PIC processing due to a modified trend of interactions between IN monomers, between IN and RT, or between IN and a cellular factor such as p75/LEDGF. 2014 Molecular therapy. Nucleic acids Discussion HIV D167A 14 19 IN;IN;IN;IN;RT;RT 53;216;237;259;96;244 55;218;239;261;98;246 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. The phenotype of HIV-1-derived vectors carrying D64V, Q168A, or N substitutions have been individually described but never compared under similar experimental conditions. 2014 Molecular therapy. Nucleic acids Discussion HIV D64V;Q168A 48;54 52;59 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. This is supported by previous experiments showing abolished or conserved replication of HIV-1 carrying either K264E or K264A IN. 2014 Molecular therapy. Nucleic acids Discussion HIV K264A;K264E 119;110 124;115 IN 125 127 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. This notion is supported by the fact that a NILV D64V+D167H also demonstrated an increased IN-independent integration as compared to a D64V vector, showing that the D167H substitution provides a gain of function independent of catalytic activity of integrase. 2014 Molecular therapy. Nucleic acids Discussion HIV D167H;D167H;D64V;D64V 54;165;49;135 59;170;53;139 IN;IN 249;91 258;93 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. This rate varied for >=2% in 9 chromosomes for D64V and LQ vectors, but in 17 chromosomes concerning vector N. 2014 Molecular therapy. Nucleic acids Discussion HIV D64V 47 51 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Vector with mutation Q168A, that reduces in vitro IN affinity for LEDGF and TNPO3, was about 15 times less integrative than WT. 2014 Molecular therapy. Nucleic acids Discussion HIV Q168A 21 26 IN 50 52 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. Viruses with IN D64V, Q168A, N, or LQ mutations are all impaired for replication due to a main defect in integration. 2014 Molecular therapy. Nucleic acids Discussion HIV D64V;Q168A 16;22 20;27 IN 13 15 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We found that vector with D64V substitution was two to six times more efficient for cell transduction than vectors Q168A, N, or LQ. 2014 Molecular therapy. Nucleic acids Discussion HIV D64V;Q168A 26;115 30;120 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. We initially chose histidine to replace a polar acid residue by a polar basic/neutral one with the purpose to induce a mild phenotype with an integration rate between WT and Q168A vectors. 2014 Molecular therapy. Nucleic acids Discussion HIV Q168A 174 179 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. When comparing the divergence of integration rate per chromosome, between WT and NILVs, it appeared that LQ, D64V, and N cumulated 21, 27, and 44% variation, respectively (Supplementary Figure S4). 2014 Molecular therapy. Nucleic acids Discussion HIV D64V 109 113 25462529 Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant. WT and D64V enzymes represented archetypical IN behaviors, with either optimal or abolished enzyme activity, in between which a continuum of transduction and integration efficiencies was observed using mutants Q168A, N, or LQ. 2014 Molecular therapy. Nucleic acids Discussion HIV D64V;Q168A 7;210 11;215 IN 45 47 25479241 HIV-1 diversity, transmission dynamics and primary drug resistance in Angola. The K103N mutation, which confers high-level resistance to nevirapine, delavirdine and efavirenz, was found in one patient accounting for a 0.7% prevalence rate of TDR which is 2.3 fold lower compared to the 2001 survey. 2014 PloS one Discussion HIV K103N 4 9 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. For instance, in this study, a K65R mutation was detected in two patients who were on TDF/ EFV treatment. 2014 BMC research notes Discussion HIV K65R 31 35 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. For NNRTI mutations, two patients had K103N and A190A. 2014 BMC research notes Discussion HIV A190A;K103N 48;38 53;43 NNRTI 4 9 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. In 20% (6/20) patient harbouring drug resistance viral strains, two patients had first TAMs mutation pathway of T215Y and also with NAMs M184V mutations. 2014 BMC research notes Discussion HIV M184V;T215Y 137;112 142;117 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. In addition, K103N mutation selected for NNRTI was also detected with high frequency in combination with M184V. 2014 BMC research notes Discussion HIV K103N;M184V 13;105 18;110 NNRTI 41 46 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. The M184V was the most predominant mutation followed K103N. 2014 BMC research notes Discussion HIV K103N;M184V 53;4 58;9 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. These mutations Y181C and G190A are known to reduce susceptibility to Etravirine which could be used either for second or third-line regimen . 2014 BMC research notes Discussion HIV G190A;Y181C 26;16 31;21 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. This mutation also occurred in combination with M184V thus reducing susceptibility to TDF and EFV . 2014 BMC research notes Discussion HIV M184V 48 53 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. Though most patients were on 3TC as first-line drug, majority of these patients failed due to the selected of M184V mutation. 2014 BMC research notes Discussion HIV M184V 110 115 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. Though mutations Y181C and G190A are mostly selected by NVP they were detected among those on EFV. 2014 BMC research notes Discussion HIV G190A;Y181C 27;17 32;22 25487529 HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. Though patient were on NVP or EFV they both selected, K103N, Y181C, A190S mutations with mutations; Y188L, A190A detected on those on NVP while Y184V, K70KT mutations on those on EFV. 2014 BMC research notes Discussion HIV A190A;A190S;K103N;K70K;K70T;Y181C;Y184V;Y188L 107;68;54;151;151;61;144;100 112;73;59;156;156;66;149;105 25488402 Modulation of HIV protease flexibility by the T80N mutation. Conversely, inhibitor-binding rigidifies the protein and the similarity of flexibility parameters obtained for all three inhibitor-containing examples and the apo T80N mutant form support the consistency and reliability of the WAXS analysis of protein flexibility. 2015 Proteins Discussion HIV T80N 163 167 25488402 Modulation of HIV protease flexibility by the T80N mutation. For these reasons we do not consider that it is very likely that there are relatively large structural differences between WT and T80N forms of HIVp in solution or that these structures deviate from the crystal structures to a large enough extent to undermine WAXS analysis. 2015 Proteins Discussion HIV T80N 130 134 25488402 Modulation of HIV protease flexibility by the T80N mutation. Furthermore, it is the experimentally observed scattering pattern from WT HIVp rather than the T80N mutant that is most dissimilar to predicted scattering patterns from (rigid) crystal structure models. 2015 Proteins Discussion HIV T80N 95 99 25488402 Modulation of HIV protease flexibility by the T80N mutation. In contrast, in our analysis and modeling protein flexibility using the vector length convolution formalism we are able to explain the scattering differences between WT and T80N HIVp based on standard crystallographic models and differences in the overall flexibility of the two molecules. 2015 Proteins Discussion HIV T80N 173 177 25488402 Modulation of HIV protease flexibility by the T80N mutation. Nevertheless, the similarity in functional form of sigma(r) as derived from both WAXS data and MD simulation, as well as the finding that the T80N mutant is globally less flexible than WT in both cases is reassuring and supports extending the global characterization of protein mobility obtained from WAXS data with the detailed atomic-level observations of protein behavior obtained from MD simulation. 2015 Proteins Discussion HIV T80N 142 146 25488402 Modulation of HIV protease flexibility by the T80N mutation. Our example calculations of scattering curves from apo and ligand-bound crystal structures show that the intensity changes that result from this scale of conformational variation (~1 A overall but larger in limited regions of the flaps) does not match the type of intensity difference that we observe between WT and T80N. 2015 Proteins Discussion HIV T80N 316 320 25488402 Modulation of HIV protease flexibility by the T80N mutation. The leading contention of this work is that the scattering differences between WT and T80N forms of HIVp are accounted for by differences in protein flexibility rather than by differences in conformation. 2015 Proteins Discussion HIV T80N 86 90 25488402 Modulation of HIV protease flexibility by the T80N mutation. This analysis of WAXS data indicates that the T80N variant exhibits less flexibility than WT across all length scales within the protein. 2015 Proteins Discussion HIV T80N 46 50 25488402 Modulation of HIV protease flexibility by the T80N mutation. WAXS patterns from WT and the functional, flap variant G48V/L63P indicate that these two forms have more global flexibility, with WT only somewhat more flexible than the double mutant. 2015 Proteins Discussion HIV G48V;L63P 55;60 59;64 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Although we found the N616 glycan to be the most important glycan in gp41 for viral infectivity, we also found a decreased viral infectivity in case of mutations N611Q and N637Q as reported by several other researchers. 2014 Retrovirology Discussion HIV N611Q;N637Q 162;172 167;177 gp41 69 73 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. However, here we show that the N674D glycan deletion led to an increase (though non-significant) in the infectivity of HIV-1NL4.3. 2014 Retrovirology Discussion HIV N674D 31 36 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. In contrast, the gp120 level in the envelope of mutant N616Q gp41 HIV-1ADA did not significantly differ from gp120 levels in WT HIV-1ADA. 2014 Retrovirology Discussion HIV N616Q 55 60 Env;gp120;gp120;gp41 36;17;109;61 44;22;114;65 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. In this respect, it should be noticed that mutant R5-tropic N616A gp41 HIV-1 strains JR-CSF, JR-FL and BG505 kept pronounced infectivity. 2014 Retrovirology Discussion HIV N616A 60 65 gp41 66 70 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Similar results were obtained for at least one gp120 glycan-deletion (N156Q mutation in the V1/V2 region), where gp120/gp41 levels were reduced by 75% in the virus particle whereas the capture efficiency was unaffected (unpublished observations). 2014 Retrovirology Discussion HIV N156Q 70 76 gp120;gp120;gp41 47;113;119 52;118;123 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. The N674D mutation that appeared in virus strains from the selection experiments using a combination of HHA and 2G12 could possibly be a rescue mutation. 2014 Retrovirology Discussion HIV N674D 4 9 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. Therefore, we believe that the decreased viral infectivity seen in the mutant N616Q gp41 strains NL4.3, IIIB and HE was caused by a compromised biosynthesis or trafficking of the envelope glycoproteins due to the N616Q glycan deletion in gp41. 2014 Retrovirology Discussion HIV N616Q;N616Q 78;213 83;218 Env;gp41;gp41 179;84;238 187;88;242 25499264 The role of N-glycans of HIV-1 gp41 in virus infectivity and susceptibility to the suppressive effects of carbohydrate-binding agents. We therefore cannot exclude that the appearance of the N674D mutation in a background of gp120 mutations was merely a secondary mutation aiming to increase the infectivity of the resistant virus strain again, instead of a mutation that was directly the consequence of targeted pressure by HHA/2G12 and meant to increase the drug resistance level. 2014 Retrovirology Discussion HIV N674D 55 60 gp120 89 94 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. In a repeated low-dose rectal transmission model, a larger inoculum was needed to successfully infect macaques with a SHIV variant containing M184V, indicating that mucosal transmissibility of the M184V variant is lower than wild type. 2014 Retrovirology Discussion HIV M184V;M184V 142;197 147;202 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. In addition, we investigated transmission of HIV-K103N and HIV-M184T as controls. 2014 Retrovirology Discussion HIV K103N;M184T 49;63 54;68 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. In our HIV transmission model, the infection of and transmission by primary DCs and LCs of HIV-K103N was consistently higher than the HIV-M184 variants. 2014 Retrovirology Discussion HIV K103N 95 100 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Indeed, the Swiss HIV cohort study described a lower prevalence of HIV-M184V in acutely infected HIV individuals compared to chronically infected patients. 2014 Retrovirology Discussion HIV M184V 71 76 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. It has been known for a long time that the RC of HIV harboring M184V/I/T is reduced in primary T cells. 2014 Retrovirology Discussion HIV M184I;M184T;M184V 63;63;63 72;72;72 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. K103N and M184V are both frequently observed in patients experiencing therapy failure, but whereas M184V is rarely detected in newly diagnosed patients, K103N is often observed. 2014 Retrovirology Discussion HIV K103N;M184V;M184V;K103N 153;10;99;0 158;15;104;5 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. M184V is known to revert rapidly after transmission. 2014 Retrovirology Discussion HIV M184V 0 5 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Our results are in line with a study that compared transmission of SHIV wild type and M184V in rhesus macaques. 2014 Retrovirology Discussion HIV M184V 86 91 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. Remarkably, the level of infection of DCs by the K103N mutant was even higher than HIV-WT in the majority of donors. 2014 Retrovirology Discussion HIV K103N 49 54 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. The frequently observed NNRTI-related mutation K103N has been described as having a modest impact on RC by several, but not all previous studies. 2014 Retrovirology Discussion HIV K103N 47 52 NNRTI 24 29 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. This may contribute to the discrepancy of the prevalence of M184V in treatment-experienced and naive individuals. 2014 Retrovirology Discussion HIV M184V 60 65 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. We compared transmission of wild type HIV with HIV-M184V in an HIV transmission model containing primary human LCs or DCs. 2014 Retrovirology Discussion HIV M184V 51 56 25499671 Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model. We have previously demonstrated that the impact of M184VIT is more pronounced in primary cells containing low levels of dNTPs. 2014 Retrovirology Discussion HIV M184I;M184T;M184V 51;51;51 58;58;58 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Certainly, further study is needed to determine how the V179D/E-associated polymorphisms affect the replication fitness of CRF01_AE HIV-1 strains. 2014 BMC infectious diseases Discussion HIV V179D;V179E 56;56 63;63 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Fifty-seven samples had at least one TDR-associated mutation, mainly including L10I/V (6.3%), A71L/T/V (6.3%), V179D/E (5.4%), and V106I (2.7%), with different distributions of TDR-associated mutations by different HIV-1 subtypes and by sample year. 2014 BMC infectious diseases Discussion HIV A71L;A71T;A71V;L10I;L10V;V106I;V179D;V179E 94;94;94;79;79;131;111;111 102;102;102;85;85;136;118;118 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. found that V179D (a NNRTI resistance mutation) significantly reduced the replication capacity of HIV-1. 2014 BMC infectious diseases Discussion HIV V179D 11 16 NNRTI 20 25 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Here, our co-variation analysis showed that V179D/E was significantly associated with seven polymorphisms in the HIV-1 CRF01_AE genotype. 2014 BMC infectious diseases Discussion HIV V179D;V179E 44;44 51;51 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. In another study by our team, we had applied the CorMut algorithm to investigate the association between drug resistance and compensatory mutations, and demonstrated that K101Q, H221Y, and T139K can enhance K103N/Y181C/G190A-associated NNRTI-resistance among CRF07_BC in vitro. 2014 BMC infectious diseases Discussion HIV G190A;K103N;Y181C;H221Y;K101Q;T139K 219;207;213;178;171;189 224;212;218;183;176;194 NNRTI 236 241 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. Nonetheless, the most frequent mutations L10I/V and V179D/E appeared to be conserved; the latter was found in 9 out of 11 CRF01_AE strains with drug resistance mutations to NNRTI drugs. 2014 BMC infectious diseases Discussion HIV L10I;L10V;V179D;V179E 41;41;52;52 47;47;59;59 NNRTI 173 178 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. The relative prevalence of V179D/E bears further remark. 2014 BMC infectious diseases Discussion HIV V179D;V179E 27;27 34;34 25510523 HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naive MSM from 2011 to 2013 in Beijing, China. These polymorphisms may serve to compensate the replication disadvantage of V179D/E, allowing this TDR-associated mutation to be propagated in treatment-naive patients. 2014 BMC infectious diseases Discussion HIV V179D;V179E 76;76 83;83 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. A detailed analysis of the X-ray crystal structure in addition to molecular dynamics simulations provides explanations for how the mutations Gly48Thr and Leu89Met confer SQV resistance. 2015 Biochemistry Discussion HIV G48T;L89M 141;154 149;162 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Although in this study of PRG48T/L89M-SQV Val82 has not been substituted with the shorter alanine, its side chain has rotated 156 , effectively resulting in the loss of three vdw interactions with P1 Phe of SQV. 2015 Biochemistry Discussion HIV L89M 33 37 PR 26 28 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Curiously, PRG48T/L89M-SQV exhibits increases in stabilizing interactions in various regions of the dimerization domain. 2015 Biochemistry Discussion HIV L89M 18 22 PR 11 13 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In Gly48Val, loss of SQV binding is attributed to the loss of a hydrogen bond between the carbonyl oxygen of 48 and the amide of SQV. 2015 Biochemistry Discussion HIV G48V 3 11 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. In the S2' subsite of PRG48T/L89M-SQV, the P2' tert-butyl group is less tightly packed in the binding pocket of PRG48T/L89M-SQV, as indicated by the loss of one vdw contact. 2015 Biochemistry Discussion HIV L89M;L89M 29;119 33;123 PR;PR 22;112 24;114 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Interestingly, we observe a similar effect in PRG48T/L89M-SQV. 2015 Biochemistry Discussion HIV L89M 53 57 PR 46 48 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. It appears that the 13% increase in active site volume calculated by CastP most likely reflects the expansion of subsites S1, S3, and S2', since it is in these cavities that losses of vdw contacts and a H-bond between SQV and PR are observed in PRG48T/L89M-SQV. 2015 Biochemistry Discussion HIV L89M 252 256 PR;PR 226;245 228;247 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. It is not difficult to conceive that PRG48T/L89M exhibits decreased susceptibility to SQV given that HIV-1 PR mutants containing Gly48Val or Gly48Val/Leu90Met demonstrate 13.5- and 419-fold reductions of susceptibility to SQV, respectively. 2015 Biochemistry Discussion HIV G48V;G48V;L89M;L90M 141;129;44;150 149;137;48;158 PR;PR 37;107 39;109 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Less intuitive is how the secondary mutation, Leu89Met, confers inhibitor resistance. 2015 Biochemistry Discussion HIV L89M 46 54 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. Our data indicate that the loss and redistribution of vdw forces resulting from the Leu89Met substitution, relative to PRWT-SQV, perturbs the hydrophobic sliding mechanism resulting in the inability of PRG48T/L89M-SQV to fully attain a closed conformation. 2015 Biochemistry Discussion HIV L89M;L89M 209;84 213;92 PR 202 204 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The Leu89Met mutation is located within the hydrophobic core of PR and plays an important role in the hydrophobic sliding mechanism. 2015 Biochemistry Discussion HIV L89M 4 12 PR 64 66 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. The S3 subsite is directly influenced by the Gly48Thr substitution that results in the loss of a hydrogen bond between N1-H of the quinolone of SQV and the main chain carbonyl of Gly48. 2015 Biochemistry Discussion HIV G48T 45 53 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. This suggests that even in light of a more stable dimeric PR, PRG48T/L89M still exhibits considerable resistance to several PIs due to its structural anomalies. 2015 Biochemistry Discussion HIV L89M 69 73 PI;PR;PR 124;58;62 127;60;64 25513833 Defective hydrophobic sliding mechanism and active site expansion in HIV-1 protease drug resistant variant Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding potency. We have described the structural analysis of a previously uncharacterized drug resistant variant PRG48T/L89M in complex with SQV. 2015 Biochemistry Discussion HIV L89M 104 108 PR 97 99 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. A major limitation of 454 and PGM sequencing is homopolymer read error, which has been associated with false positive detection of K65R in HIV-1 subtype C using the 454 platform. 2015 Journal of clinical virology Discussion HIV K65R 131 135 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. Interestingly, NVP-containing regimens have been associated with an increased risk of K65R detection, but the mechanism has not yet been described. 2015 Journal of clinical virology Discussion HIV K65R 86 90 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. Interestingly, the frequency of K65R in our study was higher in PGM reads than MiSeq, suggesting that homopolymer read error contributed to K65R variant calling. 2015 Journal of clinical virology Discussion HIV K65R;K65R 32;140 36;144 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. Nevertheless, K65R was also present, albeit at lower frequency, in MiSeq and clonal sequences. 2015 Journal of clinical virology Discussion HIV K65R 14 18 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. Overall, while HIV-1 subtype C has an increased risk of K65R under drug pressure, the extent to which these K65R mutations are from reverse transcription error in vitro or in vivo, is unclear. 2015 Journal of clinical virology Discussion HIV K65R;K65R 56;108 60;112 RT 132 153 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. Previous reports have indicated that using high fidelity PCR enzymes could limit the proportion of K65R minor variants, but despite our use of high fidelity PCR, we detected K65R > 0.5% in all infants, which might be unexpected in a tenofovir-naive cohort. 2015 Journal of clinical virology Discussion HIV K65R;K65R 99;174 103;178 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. The additional detection of Y181C in the infant, where only K103N was detected by bulk sequencing, would reduce susceptibility to the second-line NNRTI, etravirine. 2015 Journal of clinical virology Discussion HIV K103N;Y181C 60;28 65;33 NNRTI 146 151 25542470 Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. The higher coverage, and higher read quality obtained in MiSeq data may have contributed to detecting an additional patient with a minor variant DRM (G190E, in patient A300) compared to PGM. 2015 Journal of clinical virology Discussion HIV G190E 150 155 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. However, the modified W427S gp120 elicited higher levels of specific binding antibodies as well as nAbs though it produces less Tfh cells. 2014 PloS one Discussion HIV W427S 22 27 gp120 28 33 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. In our study, we found that W427S gp120 induced better nAb responses and higher levels of gp120-specific binding Abs compared with its wild-type counterpart. 2014 PloS one Discussion HIV W427S 28 33 gp120;gp120 34;90 39;95 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. In the present study, we modified the envelope of an HIV-1 primary R5 strain by substitution of 427W with S and immunized BALB/c mice using the DNA prime-protein boost strategy. 2014 PloS one Discussion HIV W427S 96 107 Env 38 46 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. The frequency of memory B cells was similar among immunized animals with wide-type or W427S mutant gp120 (data not shown). 2014 PloS one Discussion HIV W427S 86 91 gp120 99 104 25546013 An HIV-1 envelope immunogen with W427S mutation in CD4 binding site induced more T follicular helper memory cells and reduced non-specific antibody responses. We designed a mutant of gp120, W427S, which has been known as the CD4-binding deficient and CD4BS-antibody-binding competent. 2014 PloS one Discussion HIV W427S 31 36 gp120 24 29 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. As shown in Table 3, the Y115F RT enzyme incorporates CTP more efficiently than WT RT by specifically increasing the binding affinity to CTP by 13-fold without compromising either the binding to the canonical dCTP substrate or the conformational change/chemistry step. 2015 Antiviral research Discussion HIV Y115F 25 30 RT;RT 31;83 33;85 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. This bolsters the hypothesis that both the loss of the hydroxyl group in tyrosine in the Y115F mutant and the absence of a 3'-OH in 3'dCTP allows a non-canonical substrate to bind as tightly as the canonical dCTP in a mutant enzyme. 2015 Antiviral research Discussion HIV Y115F 89 94 25557601 Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template. When the hydroxyl group is absent (Y115F mutant), the binding affinity of 3'dCTP to Y115 RT is almost as high as the canonical dCTP to WT RT. 2015 Antiviral research Discussion HIV Y115F 35 41 RT;RT 89;138 91;140 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. A striking example is M46L. 2014 Retrovirology Discussion HIV M46L 22 26 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Although the single presence of M46L in HXB2 causes a large decrease in viral RC, this defect in RC is largely restored when M46L is present in a patient-derived genetic background. 2014 Retrovirology Discussion HIV M46L;M46L 32;125 36;129 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. As a single mutation, M41L in the background of wild type virus HXB2 decreased the RC. 2014 Retrovirology Discussion HIV M41L 22 26 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Certain resistance mutations such as M46I in protease have been described to decrease recognition of epitopes by certain HLA types. 2014 Retrovirology Discussion HIV M46I 37 41 PR 45 53 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Even when K103N is present as minority variant, it can contribute to therapy failure. 2014 Retrovirology Discussion HIV K103N 10 15 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. For the frequently observed NNRTI-resistance mutation K103N, it is well-known that it causes high levels of resistance against all first generation NNRTIs. 2014 Retrovirology Discussion HIV K103N 54 59 NNRTI;NNRTI 28;148 33;154 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Fortunately, the recently approved second-generation NNRTIs remain active against HIV-1 harboring a single K103N. 2014 Retrovirology Discussion HIV K103N 107 112 NNRTI 53 59 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In contrast, we have demonstrated that the NRTI-related M41L in RT has limited impact on selection of resistance against currently used NRTIs. 2014 Retrovirology Discussion HIV M41L 56 60 NRTI;NRTI;RT 43;136;64 47;141;66 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In our patients, the vast majority of TDRM persisted for at least a year and up to eight years, confirming observations from previous studies that except for M184V/I, TDRM generally persist for longer than one year. 2014 Retrovirology Discussion HIV M184I;M184V 158;158 165;165 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. In sharp contrast, pM41L + T69S + L210E + T215S, the patient-derived virus with an extensive profile containing a M41L in the presence of the compensatory mutation V60I had a similar RC as wild type virus. 2014 Retrovirology Discussion HIV L210E;M41L;T215S;T69S;V60I 34;114;42;27;164 39;118;47;31;168 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Indeed, the RC of patient-derived K103N was similar to WT virus, indicating that polymorphisms can restore viral RC. 2014 Retrovirology Discussion HIV K103N 34 39 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Interestingly, when present as a SDM in the commonly used lab strain HXB2, K103N decreased the RC in our experiments although this NNRTI-related mutation has been described to have a low impact in several but not all previous studies. 2014 Retrovirology Discussion HIV K103N 75 80 NNRTI 131 136 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. M41L is one of the most frequently observed TDRM, and is an intriguing example emphasizing the impact of the genetic background on RC. 2014 Retrovirology Discussion HIV M41L 0 4 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. M46I/L or L90M as a single TDRM in protease may cause low level resistance to commonly used protease inhibitors such as lopinavir. 2014 Retrovirology Discussion HIV L90M;M46L;M46I 10;0;0 14;6;6 PR;PR 35;92 43;100 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. Of the investigated site-directed mutant viruses, T215Y is known to evolve to atypical or partial revertant amino acids. 2014 Retrovirology Discussion HIV T215Y 50 55 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. This decrease was even more pronounced in the genetic background of pM41L, which was specifically selected for this study because of the absence of known compensatory mutations V60I and S162A. 2014 Retrovirology Discussion HIV S162A;V60I 186;177 191;181 25575025 Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity. This may explain the in vivo persistence of K103N in our and previous studies. 2014 Retrovirology Discussion HIV K103N 44 49 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. 1), while strain G3C and G3D seem to circulate only in Nigeria. 2015 AIDS research and human retroviruses Discussion HIV G3C;G3D 17;25 20;28 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. A rare treatment-associated mutation K53Y, the polymorphic mutation A71V, as well as the PI-selected mutation I85V were also found in one sample each. 2015 AIDS research and human retroviruses Discussion HIV A71V;I85V;K53Y 68;110;37 72;114;41 PI 89 91 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. A study has shown that the polymorphic mutation M36I in the PR region was associated with a higher rate of PI treatment failure. 2015 AIDS research and human retroviruses Discussion HIV M36I 48 52 PI;PR 107;60 109;62 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. For example, in the G3 cluster, there are possibly four different strains, denoted as G3A-D. 2015 AIDS research and human retroviruses Discussion HIV G3A 86 89 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. For instance, K20I in the PR region was present in all subtypes and CRFs except for eight sequences that were all subtype A-containing recombinants. 2015 AIDS research and human retroviruses Discussion HIV K20I 14 18 PR 26 28 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. In addition, we found that mutations E35D, N37DST, R57K, and K70R in the PR and D123N and I135TV in the RT were present at high rates in this cohort. 2015 AIDS research and human retroviruses Discussion HIV D123N;E35D;I135T;I135V;K70R;N37D;N37S;N37T;R57K 80;37;90;90;61;43;43;43;51 85;41;96;96;65;49;49;49;55 PR;RT 73;104 75;106 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. In the protease region, one sample displayed the K43T mutation, which was associated with a decreased virological response to tipranavir boosted with ritonavir (TPV/r) in the RESIST trials. 2015 AIDS research and human retroviruses Discussion HIV K43T 49 53 PR 7 15 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. One sample harbored the M46L mutation, which is a primary mutation inducing an intermediate level of resistance to NFV. 2015 AIDS research and human retroviruses Discussion HIV M46L 24 28 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Six specimens had the T74S mutation that induces a potential low level of resistance [classified as sensitive per the World Health Organization (WHO) interpretation] to PIs. 2015 AIDS research and human retroviruses Discussion HIV T74S 22 26 PI 169 172 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. Subtype G, CRF43-02G, and CRF06-cpx viruses utilized the codon GTG/GTA to encode valine and more likely to develop V179E mutations, whereas other CRF viruses are biased toward V179I and V179D. 2015 AIDS research and human retroviruses Discussion HIV V179D;V179E;V179I 186;115;176 191;120;181 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. The analysis of the mutational pattern suggests that the V179I mutation in the RT is not only the preferred mutation in subtype B viruses, but also occurs in non-B subtypes and CRFs. 2015 AIDS research and human retroviruses Discussion HIV V179I 57 62 RT 79 81 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. The polymorphic mutations M36I, L63P, V82I, and M89I were proportionately present in the sequences of CRF02-AG, CRF43-02G, and CRF06-cpx and subtype G. 2015 AIDS research and human retroviruses Discussion HIV L63P;M36I;M89I;V82I 32;26;48;38 36;30;52;42 25582324 Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria. This pattern of amino acid substitution by a single nucleotide change is called quasisynonymy; it may explain the high rate of the V179E found in subtype G and CRF06-cpx in this cohort and is concordant with published data and statistics predicting the occurrence of this mutation at RT position 179 of these viruses. 2015 AIDS research and human retroviruses Discussion HIV V179E 131 136 RT 284 286 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Although K92M and Y88F exhibited a decrease in Bmax and Kd values of [3H]WIN35,428 binding, their surface DAT expression was not altered, suggesting that the decreased Vmax in these mutants is not due to DAT internalization. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y88F 9;18 13;22 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Compared to WT hDAT, only Y470A and K92M decreased the Vmax of [3H]DA uptake without changing in the Km. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y470A 36;26 40;31 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. In contrast, K92M had an increase in the DA uptake potency of cocaine, GBR12909 and WIN35,428, whereas Y88F only increased the potency of cocaine and GBR12909. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y88F 13;103 17;107 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. In the present study, Y88F, K92M, Y470F and Y470A did not affect Zn2+-induced inhibition of [3H]DA uptake but diminished Zn2+-augmented [3H]WIN 35,428 binding compared to WT hDAT. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y470A;Y470F;Y88F 28;44;34;22 32;49;39;26 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Interestingly, mutant Y470A produces a similar increase in basal efflux levels for both DA and MPP+, whereas Y470F had no effect on both DA and MPP+ efflux. 2015 Journal of neuroimmune pharmacology Discussion HIV Y470A;Y470F 22;109 27;114 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Mutation of Tyr470 (Y470H) leads to transporter conformational transition by affecting zinc modulation of DA uptake and WIN binding as well as enhancing basal DA efflux. 2015 Journal of neuroimmune pharmacology Discussion HIV Y470H 20 25 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The computational predictions were validated by experimental data showing that Y88F and K92M attenuate Tat-induced inhibition of DAT. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y88F 88;79 92;83 Tat 103 106 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The present results show that K92M but not Y88F decreased the Vmax with no changes in Km values; however, both mutants slightly increased IC50 values for DA inhibiting DA uptake compared to WT hDAT. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y88F 30;43 34;47 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The present results show that Y470A but not Y470F also attenuated Tat-induced inhibition on DAT because mutating Tyr470 to phenylalanine (Y470F) does not affect the cation-pi interaction. 2015 Journal of neuroimmune pharmacology Discussion HIV Y470A;Y470F;Y470F;Y470F 30;44;138;113 35;49;143;136 Tat;PI 66;172 69;174 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. The present study confirmed Y470H-mediated enhancement of basal DA and MPP+ efflux, which is consistent with our previous report. 2015 Journal of neuroimmune pharmacology Discussion HIV Y470H 28 33 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. These data are consistent with our previous finding showing an increase in the DA uptake potency of cocaine and GBR12909 in Y470H. 2015 Journal of neuroimmune pharmacology Discussion HIV Y470H 124 129 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. We have demonstrated that Y470H exhibits a reduction of the Vmax with no changes in Km; however, the current data show that Y470A but not Y470F decreased the Vmax without changing Km value because Y470F did not affect the hydrophobic property of Y470. 2015 Journal of neuroimmune pharmacology Discussion HIV Y470A;Y470F;Y470F;Y470H 124;138;197;26 129;143;202;31 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. With regard to mutations of Tyr88 and Lys92, only K92M displayed an increase in basal efflux of DA but not MPP. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M 50 54 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. With regard to the potency for [3H]WIN35,428 binding, Y88F and K92M increased IC50 value of DA, whereas only Y88F decreased IC50 of cocaine. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y88F;Y88F 63;54;109 67;58;113 25604666 Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport. Y88F and K92M decreased the potency for cocaine and GBR12909 but increased the affinity for DA in both [3H]DA uptake and [3H]WIN35,428 binding, suggesting that mutations of these residues in hDAT disrupt the binding sites for DA and inhibitors. 2015 Journal of neuroimmune pharmacology Discussion HIV K92M;Y88F 9;0 13;4 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. In fact, we have found the mutations to be M184V, K103N, and Y181C. 2015 Global health action Discussion HIV K103N;M184V;Y181C 50;43;61 55;48;66 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. K103N mutation causes high resistance to NVP and EFV, as found in our study, although we have not been able to sequence all our samples. 2015 Global health action Discussion HIV K103N 0 5 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. Moreover, an identical mutation (Y181C) found by Nadembega et al. 2015 Global health action Discussion HIV Y181C 33 38 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. Several other studies reported that K103N was highly prevalent among NNRTI-associated resistance mutations . 2015 Global health action Discussion HIV K103N 36 41 NNRTI 69 74 25630709 Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance. showed that, in addition to the mutations in the RT (Y18CY), other major protease mutations such as V8IV induced a selection of resistant viral strains. 2015 Global health action Discussion HIV V8I;V8V;Y18C;Y18Y 100;100;53;53 104;104;58;58 PR;RT 73;49 81;51 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. A similar prevalence of K65R, compared to Hoffmann et al. 2015 PloS one Discussion HIV K65R 24 28 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. A study conducted in Nigeria suggested that TDF-exposed patients infected with HIV-1 subtype G or CRF02_AG were less likely to develop K65R (14%). 2015 PloS one Discussion HIV K65R 135 139 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Despite the NRTI cross-resistance caused by K65R, most patients remained susceptible to AZT regardless of d4T or TDF-exposure. 2015 PloS one Discussion HIV K65R 44 48 NRTI 12 16 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. have previously shown an antagonistic association between TAMs and K65R. 2015 PloS one Discussion HIV K65R 67 71 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. However, the high prevalence of the K65R mutation leaves few choices to recycle NRTIs in third-line and salvage regimens. 2015 PloS one Discussion HIV K65R 36 40 NRTI 80 85 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. In the latter study a K65R prevalence of 23% was detected among patients presenting with at least one drug resistance mutation. 2015 PloS one Discussion HIV K65R 22 26 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. In vitro experiments with TDF-3TC exposure showed that Y115F is commonly selected after the development of K65R, which is reflected in our data as K65R was present in nine out of 11 of the patients with Y115F. 2015 PloS one Discussion HIV K65R;K65R;Y115F;Y115F 107;147;55;203 111;151;60;208 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. More than half of the patients failing a TDF-based regimen developed the K65R mutation as compared to only 8.8% in the d4T-group, which translates into an almost 5-fold risk of developing K65R after TDF exposure. 2015 PloS one Discussion HIV K65R;K65R 73;188 77;192 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Overall, these results demonstrate that the frequency of the K65R mutation is higher in South African HIV-1 subtype C infected patients when compared to other countries where non-subtype C viruses dominate the epidemic. 2015 PloS one Discussion HIV K65R 61 65 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Similar results were observed by two recent South African studies, whereas the prevalence of K65R was substantially lower in a third South African study. 2015 PloS one Discussion HIV K65R 93 97 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Similarly, K65R was only found in 17% of TDF-experienced subtype B infected patients. 2015 PloS one Discussion HIV K65R 11 15 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. The high frequency of K65R in our study was expected, as 98% of the study population was infected with a subtype C virus and the development of K65R is subtype dependent. 2015 PloS one Discussion HIV K65R;K65R 22;144 26;148 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. The sole presence of K65R causes intermediate resistance to TDF whereas the combination with Y115F increases the level of resistance, as was observed in 10% of the TDF-exposed patients. 2015 PloS one Discussion HIV K65R;Y115F 21;93 25;98 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. This was confirmed by our data as only 6.2% and 1.2% of the patients, exposed to TDF and d4T respectively, developed both K65R and TAMs. 2015 PloS one Discussion HIV K65R 122 126 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. This Y115F mutation is known to develop under ABC pressure, however none of the patients in our study population were exposed to ABC. 2015 PloS one Discussion HIV Y115F 5 10 25659108 High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. Y115F was absent in the d4T-exposed patients and detected in 13.8% of the TDF-exposed patients, which confirms the findings of a recent South African study. 2015 PloS one Discussion HIV Y115F 0 5 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. A recent report has shown that the A400T mutation reduces RNase H activity while producing a small increase in resistance to nevirapine and efavirenz. 2015 Nucleic acids research Discussion HIV A400T 35 40 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. A recent search in the Stanford HIV Drug Resistance Database (http://hivdb.stanford.edu/; accessed on 22 September 2014) showed that the prevalence of N348I and T369I in untreated patients infected with HIV-1 group M subtype B was lower than 0.1%, while in patients treated with nevirapine, these figures went up to 11.1 and 1.5% for N348I and T369I, respectively (P < 0.001 in both cases). 2015 Nucleic acids research Discussion HIV N348I;N348I;T369I;T369I 151;334;161;344 156;339;166;349 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Although N348I and more efficiently N348I/T369I could revert some of the effects of NNRTIs on PPT removal, their efficiency with rilpivirine is almost negligible. 2015 Nucleic acids research Discussion HIV N348I;N348I;T369I 9;36;42 14;41;47 NNRTI 84 90 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Another important conclusion of these experiments is that rilpivirine seems to be effective in promoting the degradation of the PPT and inhibiting its extension in the presence of dNTPs, being almost equally effective against the WT enzyme and the double mutant N348I/T369I. 2015 Nucleic acids research Discussion HIV N348I;T369I 262;268 267;273 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. However, it is clear from our studies that when associated with RNA/DNA complexes, the combination of mutations N348I and T369I has a major impact in the RNase H activity of the RT. 2015 Nucleic acids research Discussion HIV N348I;T369I 112;122 117;127 RT 178 180 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. However, the differences between WT and N348I/T369I RT were more pronounced with nevirapine. 2015 Nucleic acids research Discussion HIV N348I;T369I 40;46 45;51 RT 52 54 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. However, when the PPT sequence resistant to hydrolysis was made one or two nucleotides shorter, the differences in cleavage patterns between WT and N348I/T369I RTs became evident. 2015 Nucleic acids research Discussion HIV N348I;T369I 148;154 153;159 RT 160 163 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. In addition, experiments carried out with the 29/28mer hybrid showed that the double mutant had significantly reduced efficiency in the generation of shorter RNAs, in comparison with the WT RT or the single mutants T369I, T369V and T376S. 2015 Nucleic acids research Discussion HIV T369I;T369V;T376S 215;222;232 220;227;237 RT 190 192 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. In addition, recent studies have shown that N348I produces a moderate increase (around 2-fold) in the levels of rilpivirine resistance conferred by E138K, although the reduced DNA polymerase and RNase H activities of the N348I mutant restrict the emergence of the rilpivirine resistance mutation due to the diminished replication capacity of the virus. 2015 Nucleic acids research Discussion HIV E138K;N348I;N348I 148;44;221 153;49;226 Pol 180 190 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Modeling studies have shown little differences between ternary complexes containing the WT or the double-mutant N348I/T369I RT, associated with a DNA/DNA template-primer and nevirapine. 2015 Nucleic acids research Discussion HIV N348I;T369I 112;118 117;123 RT 124 126 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Moreover, the likely increased rigidity caused by mutations such as N348I imposes constraints in the structure of the NNRTI binding pocket. 2015 Nucleic acids research Discussion HIV N348I 68 73 NNRTI 118 123 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Nevertheless, nevirapine and efavirenz are strong enhancers of the PPT removal reaction (Figure 2A), while N348I and in a larger extent N348I/T369I counteract these effects. 2015 Nucleic acids research Discussion HIV N348I;N348I;T369I 107;136;142 112;141;147 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Nevertheless, we also found that T369I enhances the effects of N348I RT by producing a further reduction of its RNase H activity. 2015 Nucleic acids research Discussion HIV N348I;T369I 63;33 68;38 RT 69 71 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Our data confirm that initiation of (+)-strand DNA synthesis during reverse transcription is significantly affected by N348I, but we also show that other individual mutations in the RT connection subdomain such as T369I or V or T376S do not seem to affect PPT removal. 2015 Nucleic acids research Discussion HIV N348I;T369I;T376S 119;214;228 124;219;233 RT;RT 68;182 89;184 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Our studies with RNA/DNA complexes of different lengths show for the first time that N348I influences the RNase H cleavage window and that this effect is enhanced by the presence of T369I. 2015 Nucleic acids research Discussion HIV N348I;T369I 85;182 90;187 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Reduced RNase H activity mediated by N348I and other mutations in its vicinity increases the stability of the RT/template-primer/NNRTI complex and therefore allows more time for dissociation of the NNRTI from the RT/template-primer binary complex. 2015 Nucleic acids research Discussion HIV N348I 37 42 NNRTI;NNRTI;RT;RT 129;198;110;213 134;203;112;215 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Significant increases of prevalence were also observed for patients treated with efavirenz where N348I and T369I were present in 8.7% and 2.2% of all isolates, respectively (P < 0.001). 2015 Nucleic acids research Discussion HIV N348I;T369I 97;107 102;112 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Similar analyses carried out with T369V and A376S only reveal a significant increase of prevalence in the case of T369V and nevirapine (8.8% in nevirapine-treated patients versus 3.0% in untreated individuals). 2015 Nucleic acids research Discussion HIV A376S;T369V;T369V 44;34;114 49;39;119 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The different cleavage windows finally result in the conservation of the PPT primer in the presence of nevirapine, etravirine and efavirenz, and a higher efficiency of (+)-strand DNA synthesis in reactions catalyzed by the double-mutant N348I/T369I. 2015 Nucleic acids research Discussion HIV N348I;T369I 237;243 242;248 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The lower replication capacity of HIV-1 bearing RT mutations N348I/T369I could be attributed to the reduced RNase H cleavage efficiency of the N348I/T369I RT observed in our studies with PPT-containing template-primers as well as conventional heteropolymeric hybrids. 2015 Nucleic acids research Discussion HIV N348I;N348I;T369I;T369I 61;143;67;149 66;148;72;154 RT;RT 48;155 50;157 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The results obtained with the WT RT and the single-mutant N348I RT in the presence of nevirapine and efavirenz are similar to those previously reported by Biondi et al., although in their assays the suppressive effect of N348I was observed only with nevirapine. 2015 Nucleic acids research Discussion HIV N348I;N348I 58;221 63;226 RT;RT 33;64 35;66 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. The studied amino acid substitutions had a relatively small impact on NNRTI resistance (Table 1), but the combination of N348I and T369I was previously described as conferring a serious defect in viral replication capacity. 2015 Nucleic acids research Discussion HIV N348I;T369I 121;131 126;136 NNRTI 70 75 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Unlike mutations analyzed in our study whose prevalence in untreated patients is lower than 7.5%, A400T is a common polymorphism in HIV-1 group M isolates with a prevalence of nearly 56% in untreated patients. 2015 Nucleic acids research Discussion HIV A400T 98 103 25662223 Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. WT and N348I/T369I RTs had similar efficiencies and cleavage patterns when RNA products of 21 nucleotides were generated. 2015 Nucleic acids research Discussion HIV N348I;T369I 7;13 12;18 RT 19 22 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Also, K101E and G190A mutations, documented to cause high level resistance to nevirapine and efavirenz (NNRTI inhibitors), were detected in a naive patient (AIIMSPD11). 2015 Viruses Discussion HIV G190A;K101E 16;6 21;11 NNRTI 104 109 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. L10I is a polymorphic accessory mutation in the protease gene that is associated with reduced susceptibility to protease inhibitor. 2015 Viruses Discussion HIV L10I 0 4 PR;PR 48;112 56;120 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Sehgal et al., 2008, reported a high incidence of K103N mutation in ART naive (33%) children and in those who had received a nevirapine containing regimen (56%). 2015 Viruses Discussion HIV K103N 50 55 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. The presence of L10I mutation in an ART naive patient (AIIMSPDU40) is suggestive of the presence of such baseline transmitted mutations in the protease gene of HIV-1 in children, hence, screening for these mutations before initiating protease inhibitor treatment would be beneficial. 2015 Viruses Discussion HIV L10I 16 20 PR;PR 143;234 151;242 25674767 Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients. Two ART naive patients, AIIMSU63 and AIIMSPD5 harbored L74I (conferring high level of resistance to didanosine; NNRTI inhibitor) and V106A (conferring high level of resistance to nevirapine; NNRTI inhibitors) mutations respectively. 2015 Viruses Discussion HIV L74I;V106A 55;133 59;138 NNRTI;NNRTI 112;191 117;196 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Although the Asn103 and Lys103 backbone conformations are similar, it is apparent that the rotation of the uracil ring observed in the RT (Y181C):1 and RT (K103N/Y181C):1 structures prevents the formation of the second hydrogen bond with the backbone of Lys103/Asn103. 2015 Journal of medicinal chemistry Discussion HIV K103N;Y181C;Y181C 156;139;162 161;144;167 RT;RT 135;152 137;154 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Although the sag conformation of 1 is optimal for RT (WT), this conformation is suboptimal for adapting to the Y181C and K103N/Y181C binding pockets by preventing hydrogen bonds with the uracil. 2015 Journal of medicinal chemistry Discussion HIV K103N;Y181C;Y181C 121;111;127 126;116;132 RT 50 52 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Analysis of the six crystal structures reveals that the Y181C mutation indirectly affects compound binding by affecting the orientation of the ethoxy linked uracil side chain. 2015 Journal of medicinal chemistry Discussion HIV Y181C 56 61 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. By comparing crystal structures of wild-type and mutant RT variants in complex with catechol diether compounds 1 and 2, it is apparent that the aag conformation of 2 is optimal for adapting in both RT (Y181C) and RT (K103N/Y181C) binding pockets. 2015 Journal of medicinal chemistry Discussion HIV K103N;Y181C;Y181C 217;202;223 222;207;228 RT;RT;RT 56;198;213 58;200;215 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Earlier comparisons of the RT (WT) and RT (Y181C) complexes with nevirapine revealed that the lost interaction between Y181 and the dipyrido-diazepine ring contributes to the 100-fold reduction in potency. 2015 Journal of medicinal chemistry Discussion HIV Y181C 43 48 RT;RT 27;39 29;41 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. For compound 2, the single backbone interaction with Lys103/Asn103 is retained in the RT (WT), RT (Y181C), and RT (K103N/Y181C) structures. 2015 Journal of medicinal chemistry Discussion HIV K103N;Y181C;Y181C 115;99;121 120;104;126 RT;RT;RT 86;95;111 88;97;113 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In both RT (K103N/Y181C):1 and RT (K103N/Y181C):2 structures, the interaction between the NH of Asn103 and the C2 carbonyl is retained, but the interaction between the backbone carbonyl of Asn103 observed in the RT (WT):1 complex is lost. 2015 Journal of medicinal chemistry Discussion HIV K103N;K103N;Y181C;Y181C 12;35;18;41 17;40;23;46 RT;RT;RT 8;31;212 10;33;214 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. In fact, the opening of the pocket entrance created by the Cys181 mutation near Lys/Asn103 may actually enhance compound entry. 2015 Journal of medicinal chemistry Discussion HIV K103N 84 90 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. On the basis of the structures, it appears that the Y181C mutation has an impact on inhibitor binding that may disrupt hydrogen bonding with the backbone of Lys103/Asn103. 2015 Journal of medicinal chemistry Discussion HIV Y181C 52 57 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Previous structural studies comparing RT (WT) and RT (K103N) enzymes postulated that the K103N mutation could restrict the entry of NNRTIs and, thus, the formation of the NNBP. 2015 Journal of medicinal chemistry Discussion HIV K103N;K103N 54;89 59;94 NNRTI;RT;RT 132;38;50 138;40;52 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. The uracil rotation observed in the RT (Y181C):1 and RT (K103N/Y181C):1 structures seems to influence the hydrogen bonding interactions with the uracil ring. 2015 Journal of medicinal chemistry Discussion HIV K103N;Y181C;Y181C 57;40;63 62;45;68 RT;RT 36;53 38;55 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. This interaction is also lost in the RT (Y181C):1 structure where Lys103 is still present. 2015 Journal of medicinal chemistry Discussion HIV Y181C 41 46 RT 37 39 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Thus, it appears that the K103N mutation is not causing structural changes in the binding pocket that prevent hydrogen bonds with the uracil ring. 2015 Journal of medicinal chemistry Discussion HIV K103N 26 31 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. To that end, we have investigated the crystal of structures Y181C and K103N/Y181C RT variants in complex with novel catechol diether NNRTIs to understand the structural impact of these mutations on inhibitor binding and potency. 2015 Journal of medicinal chemistry Discussion HIV K103N;Y181C;Y181C 70;60;76 75;65;81 NNRTI;RT 133;82 139;84 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. Unlike the Y181 mutation, the crystal structures reveal that the K103N mutation may have less of an effect on catechol diether binding. 2015 Journal of medicinal chemistry Discussion HIV K103N 65 70 25700160 Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants. We speculate that the K103N mutation does not prevent the entry of the catechol diethers because crystallization of the RT (K103N/Y181C) complexes was possible, and both compounds 1 and 2 were present at full occupancy in the refined structures. 2015 Journal of medicinal chemistry Discussion HIV K103N;K103N;Y181C 22;124;130 27;129;135 RT 120 122 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. However, the M184VI can be transmitted and may be linked with other RAMs, but tends to wane over time due to overgrowth of more fit wild-type virus. 2015 HIV medicine Discussion HIV M184I;M184V 13;13 19;19 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. Most mutations at the T215 position were revertants of the T215Y or T215F mutations, which are associated with thymidine analogue (zidovudine or stavudine) exposure. 2015 HIV medicine Discussion HIV T215F;T215Y 68;59 73;64 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. Of note, in this patient population we did not observe transmitted NRTI resistance with M184VI. 2015 HIV medicine Discussion HIV M184I;M184V 88;88 94;94 NRTI 67 71 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. Overall, transmitted protease resistance mutations were identified less frequently, with M46IL and L90M being the most common. 2015 HIV medicine Discussion HIV L90M;M46I;M46L 99;89;89 103;94;94 PR 21 29 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. Studies employing more sensitive methods of detecting RAMs such as ultra-deep sequencing have found the M184VI in treatment-naive chronically infected individuals with TDR. 2015 HIV medicine Discussion HIV M184I;M184V 104;104 110;110 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. The K103N mutation was the single most frequently identified mutation and has been commonly reported in transmitted NNRTI drug resistance in North America and Europe. 2015 HIV medicine Discussion HIV K103N 4 9 NNRTI 116 121 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. The L90M mutation has been associated with exposure to a number of PIs, but is classically associated with saquinavir and is considered a primary mutation for both saquinavir and nelfinavir. 2015 HIV medicine Discussion HIV L90M 4 8 PI 67 70 25711326 Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. The M46IL is considered a primary mutation for indinavir, but is also a common secondary mutation associated with the other PIs, except for saquinavir and darunavir. 2015 HIV medicine Discussion HIV M46I;M46L 4;4 9;9 PI 124 127 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. In matched hosts, HLA-B*57-restricted A163X escape mutation in the KF11 epitope has been shown to result in reduced plasma viral loads; while I147X compensatory mutation has been linked to restoration of ISW9 epitope recognition. 2015 Vaccine Discussion HIV A163X;I147X 38;142 43;147 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. In this study, plasma viral loads were eight-fold lower in presenting hosts bearing the A163X mutation suggesting the likelihood for potential T-cell involvement. 2015 Vaccine Discussion HIV A163X 88 93 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. Others also demonstrated higher A163X frequencies among clade A subjects. 2015 Vaccine Discussion HIV A163X 32 37 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. The higher rates of A163X mutation observed in HLA matched and mismatched clade A1 subjects in our population suggest better tolerance of those changes by clade A viruses. 2015 Vaccine Discussion HIV A163X 20 25 25728323 Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles. We combined measurements of adaptive T-cell functionality with ISW9, KF11 and TW10 Gag p24 epitope sequence data to demonstrate that the A163X mutation in KF11 was more associated with clade A1-infection; the compensatory mutation I147X, known to restore immune recognition of the ISW9 epitope, was more frequent in clade A1 subjects; but frequencies of TW10 epitope polymorphisms did not significantly vary across clades. 2015 Vaccine Discussion HIV A163X;I147X 137;231 142;236 p24;Gag 87;83 90;86 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Another interesting observation is that, while the combined mutants containing N197D/N463Q did not show continued increase of neutralizing sensitivity to nMAbs with additional PNGS mutations, these combined mutants displayed a general trend of cumulative mutational effect on the increase of neutralizing sensitivity to the serum antibodies (Table 2). 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q 79;85 84;90 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Compared with the combined PNGS mutants, only the N197D and the N442Q among the single mutants showed relatively modest increase in neutralizing sensitivity to VRC03, with N197D showing 37-fold increase and N442Q showing 3-fold to VRC03. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N197D;N442Q;N442Q 50;172;64;207 55;177;69;212 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. However, N463Q single mutant, together with most other single mutants alone, showed little effect on neutralization by VRC01/VRC03, b12 or other nMAbs (Table 1). 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N463Q 9 14 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. However, there appears to be a general trend that the observed cumulative effect to the serum antibodies become stronger when the combined mutants contain at least the N197D and N463Q mutations, which further suggests that the neutralizing antibodies in HIV-1 positive serum targeting the CD4bs and the conserved elements of V3 region may play a dominant role in neutralizing the virus for those patient serum in our assays. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q 168;178 173;183 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. In conclusion, our results indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D 152 157 gp120 170 175 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. In fact, all the seven mutants that contain both N197D and N463Q in them showed the same dramatic increase of sensitivity to VRC01/VRC03, whereas those combined mutants with N197D but without N463Q (mutants 197M.2, 197M.6, and 197M.7) showed little effect (Supplemental Table 1 & Table 1). 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N197D;N463Q;N463Q 49;174;59;192 54;179;64;197 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. In other words, even though the effect of N463Q mutation alone did little in altering the sensitivity to nMAbs VRC01/VRC03 (with ~1.5 fold increase), combining N463Q mutation with N197D has an unexpected synergistic effect in increasing the sensitivity to VRC01/VRC03 by a remarkable 300-1300 fold. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q;N463Q 180;42;160 185;47;165 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Interestingly, further mutations of the PNGS up to five sites on top of the N197D/N463Q mutation appear to have very minor additional effect on the sensitivity level to the two VRC nMAbs. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q 76;82 81;87 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. N197D also showed a 2-fold increase sensitivity to VRC01. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D 0 5 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Our previous study indicated that N197D or N301Q mutation alone did not have severe impact on the infectivity, which is also confirmed here. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N301Q 34;43 39;48 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Surprisingly, one of the twelve mutants, the double mutant 197M.1 (N197D and N301Q) resulted in a complete loss of viral infectivity, which is rather surprising considering that as all the other combined mutants contain the N197D mutation had infectivity, and some of them having additional 3 to 7 point mutations on top of N197D. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N197D;N197D;N301Q 67;224;324;77 73;229;329;82 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. The neutralization ability of CD4bs MAbs VRC03 showed a marked increase for combined PNGS mutants that contained the both N197D and N463Q mutations, with a remarkable ~800-1300 fold increase over wt FE. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q 122;132 127;137 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Thus, N463Q mutation seems to play an important role in determining the neutralizing sensitivity to nMAbs VRC01/VRC03 in the N197D mutant background. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q 125;6 130;11 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Two pairs of combined mutants 197M.2/197M.5, and 197M.7/197M.9 (Supplemental Table 1), which differ only in containing N463Q mutation or not, showed significant difference in VRC01/VRC03 sensitivity, with the mutants containing N463Q displaying much higher VRC01/03 sensitivity. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N463Q;N463Q 119;228 124;233 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. Very interestingly, the remarkable increase of sensitivity of mutants containing N463Q/N197D was only observed for nMAbs VRC01/VRC03, and not for other tested nMAbs (Table 1). 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q 87;81 92;86 25751231 N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03. We also found that combined PNGS mutations that include N197D/N463Q mutations of gp120 made the virus more readily to be neutralized by serum polyclonal antibodies from patients. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N197D;N463Q 56;62 61;67 gp120 81 86 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. A prior study of antiretroviral drug-nave HIV-1-infected Zambian adults (n=28) demonstrated a high frequency of pre-existing minor mutations in the protease gene:including I93L (92%), L89M (79%), and M36I (79%):which corroborates results from our current study (Handema et al., 2003). 2015 Journal of medical virology Discussion HIV I93L;L89M;M36I 172;184;200 176;188;204 PR 148 156 HIV infections 42 56 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. Another Zambian study compared therapy-nave patients before (n = 30) and after (n = 66) the availability of free-of-charge ART, showing no statistically significant difference in major PI DRMs (V82I: 10% vs. 2015 Journal of medical virology Discussion HIV V82I 194 198 PI 185 187 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. The most prevalent NNRTI mutations were Y181C/I/V (41%), G190A/S/E (34%), K103N/S (32%), and Y188L (7%). 2015 Journal of medical virology Discussion HIV G190A;G190E;G190S;K103N;K103S;Y181C;Y181I;Y181V;Y188L 57;57;57;74;74;40;40;40;93 66;66;66;81;81;49;49;49;98 NNRTI 19 24 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. These results are of particular relevance as Y181C/I/V and Y188L (and to a lesser extent, G190A/S/E) renders second-generation NNRTI drugs (e.g., ETR, RPV) ineffectual for potential salvage therapies. 2015 Journal of medical virology Discussion HIV G190A;G190E;G190S;Y181C;Y181I;Y181V;Y188L 90;90;90;45;45;45;59 99;99;99;54;54;54;64 NNRTI 127 132 25754408 Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia. We observed a high prevalence of the Y181C/I/V (41%) and L100I (2%), an important consideration as these NNRTI DRMs confers reduced susceptibility to the third line salvage candidate etravirine. 2015 Journal of medical virology Discussion HIV L100I;Y181C;Y181I;Y181V 57;37;37;37 62;46;46;46 NNRTI 105 110 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. 101-fold for single-cycle infection) observed for HIVTAM is completely reversed by either the K65K or the K66K silent mutation (Figure 5 and Supplementary Tables S2 and S3), we did not observe restoration of HIVTAM infectivity to WT levels in the presence of either silent mutation in a single-cycle assay (Supplementary Figure S4A). 2015 Nucleic acids research Discussion HIV K65K;K66K 94;106 98;110 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. A G) are common in HIV replication, but in the absence of drug, there is no selective pressure for the retention of either the G to A mutation that leads to the D67N change or indeed the A to G change that results in K70R at nucleotide 2758 (Figure 5C); consequently, it is unlikely that these mutations would be overrepresented in multiple-cycle infections. 2015 Nucleic acids research Discussion HIV D67N;K70R 161;217 165;221 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Although the size of the fitness gains mediated by K65K or K66K is relatively small compared to that of drug resistance mutations under selective pressure (e.g. 2015 Nucleic acids research Discussion HIV K65K;K66K 51;59 55;63 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. As such, these data do not appear to support the notion that effects on translation, expression or function of RT or codon usage biases are acting to alleviate the fitness defects caused by D67N/K70R. 2015 Nucleic acids research Discussion HIV D67N;K70R 190;195 194;199 RT 111 113 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. D67N relative to WT in the presence of ZDV), over multiple cycles of replication in vivo these small fitness gains are likely to be amplified and have clinical implications. 2015 Nucleic acids research Discussion HIV D67N 0 4 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Drug resistance mutations change the primary sequence of HIV-1, which can alter the length of homopolymeric stretches of nucleotides, as is the case for D67N in subtype B. 2015 Nucleic acids research Discussion HIV D67N 153 157 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. For example, the synonymous mutation, A759G, becomes fixed in quasispecies of the ssRNA virus, puumala virus, conferring a transmission advantage to the virus in rodent populations. 2015 Nucleic acids research Discussion HIV A759G 38 43 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Furthermore, the increased frequency of MNV resulting in the simultaneous emergence of D67N and K65K but not K70R in HIVWT during single-cycle infections suggests that this observation is unlikely to be a result of contamination with our D67N/K70R TAM containing mutants during the deep sequencing protocol. 2015 Nucleic acids research Discussion HIV D67N;D67N;K65K;K70R;K70R 87;238;96;109;243 91;242;100;113;247 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Given the subtle effect of the fitness advantage conferred by the silent mutations K65K and K66K that emerges over multiple rounds of infection, it was not surprising that we were unable to detect any differences between HIVTAM and the silent mutation-carrying variants in infectivity, steady-state levels of virion-associated RT and RT activity in virus produced by transfection (Supplementary Figures S2 and S3). 2015 Nucleic acids research Discussion HIV K65K;K66K 83;92 87;96 RT;RT 327;334 329;336 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. However, our previous RNA secondary structure modeling focusing on short HIV-1 RT templates representing codons 55-75 places K65K and K66K in a single-stranded region. 2015 Nucleic acids research Discussion HIV K65K;K66K 125;134 129;138 RT 79 81 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. However, the TAMs D67N/K70R and silent mutations are not located near known splice sites in HIV-1 and are unlikely to generate strong splice sites (unpublished data). 2015 Nucleic acids research Discussion HIV D67N;K70R 18;23 22;27 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. However, we did detect an increase in the frequency of SNV resulting in the emergence of both D67N (2.37%) and K70R (3.2%) in HIVWT (Figure 5C). 2015 Nucleic acids research Discussion HIV D67N;K70R 94;111 98;115 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Indeed, our initial observation that K65K and K66K are commonly selected in drug-treated individuals provides compelling support for this assertion. 2015 Nucleic acids research Discussion HIV K65K;K66K 37;46 41;50 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. K65K and K66K are located in the coding region of a vital HIV-1 enzyme and act by altering RTn through effects on the primary viral genome sequence. 2015 Nucleic acids research Discussion HIV K66K;K65K 9;0 13;4 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Notably, the G to A mutation at 2748 (leading to D67N change) in HIVWT during single-cycle infections is 6-fold higher than the frequency observed in the multiple-cycle infection. 2015 Nucleic acids research Discussion HIV D67N;G2748A 49;13 53;36 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Our finding that D67N/K70R confer a fitness defect in the absence of drug is consistent with previous studies, although the underlying mechanism for this defect is not well described. 2015 Nucleic acids research Discussion HIV D67N;K70R 17;22 21;26 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Our studies demonstrate a definitive role for K65K and K66K in rescuing a viral fitness defect mediated by the TAMs, D67N/K70R while having no effect on potentiating NRTI and NNRTI resistance in the context of TAMs. 2015 Nucleic acids research Discussion HIV D67N;K65K;K66K;K70R 117;46;55;122 121;50;59;126 NNRTI;NRTI 175;166 180;170 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Our study is the first to evaluate RTn errors introduced in the HIV-1 proviral DNA during virus replication mediated by the D67N/K70R TAMs and the in vivo selected K65K and K66K silent mutations using Illumina next-generation amplicon sequencing. 2015 Nucleic acids research Discussion HIV D67N;K65K;K66K;K70R 124;164;173;129 128;168;177;133 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Our study provides the first evidence that silent mutations in the HIV-1 subtype B RT selected during drug therapy in vivo can directly alleviate fitness defects in virus concurrently encoding the TAMs, D67N/K70R. 2015 Nucleic acids research Discussion HIV D67N;K70R 203;208 207;212 RT 83 85 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. revealed that RT pauses on the homopolymeric tract of eight adenines introduced by D67N/K70R, and that the silent mutations K65K or K66K alleviate this pause. 2015 Nucleic acids research Discussion HIV D67N;K65K;K66K;K70R 83;124;132;88 87;128;136;92 RT 14 16 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Similarly, the synonymous mutation A1869G, selected in cell culture, improves the genetic stability of the nonsynonymous 627K mutation, a known mammalian adaptation motif of the highly pathogenic clade 2.2 Eurasian lineage H5N1 avian influenza virus. 2015 Nucleic acids research Discussion HIV A1869G 35 41 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Specifically, the synonymous mutations, K65K and K66K, in the RT of HIV-1 subtype B alleviate fitness defects conferred by the TAMs D67N/K70R. 2015 Nucleic acids research Discussion HIV D67N;K65K;K66K;K70R 132;40;49;137 136;44;53;141 RT 62 64 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. Strikingly, the introduction of either K65K or K66K into the RNA template containing D67N/K70R reversed the propensity for RT to introduce indel mutations that could otherwise lead to the production of defective provirus. 2015 Nucleic acids research Discussion HIV D67N;K65K;K66K;K70R 85;39;47;90 89;43;51;94 RT 123 125 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. These data are congruent with the dramatically increased indels associated with HIVTAM infection and the ability of HIVTAMK65K and HIVTAMK66K to rescue this defect being a component of the underlying mechanism by which silent mutations can alleviate fitness defects conferred by D67N/K70R. 2015 Nucleic acids research Discussion HIV D67N;K70R 279;284 283;288 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. This is consistent with D67N and K70R substitutions being among the first to appear in vivo. 2015 Nucleic acids research Discussion HIV D67N;K70R 24;33 28;37 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. This is consistent with our data demonstrating that K65K and K66K in the context of D67N/K70R do not alter the susceptibility of virus to ZDV, TFV, ABC or NVP (Table 1). 2015 Nucleic acids research Discussion HIV D67N;K65K;K66K;K70R 84;52;61;89 88;56;65;93 25765644 Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations. We show using next-generation deep sequencing that the D67N/K70R TAMs in subtype B HIV-1 conferred an approximately 100-fold increase in the frequency of indel mutations within a homopolymeric region at nucleotides spanning RT codons 65-67 during single-cycle infections and approximately 61-fold increase in indels during multiple-cycle infections relative to HIVWT. 2015 Nucleic acids research Discussion HIV D67N;K70R 55;60 59;64 RT 224 226 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. Because the selection of self-ligands during thymic education are likely different depending on the HLA type, we speculate that HLA-B*07:02 expressing individuals may select a TCR, sensitive to the R71K mutation, that is not selected in HLA-B*42:01/42:02/81:01 positive individuals. 2015 Retrovirology Discussion HIV R71K 198 202 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. TCR structures obtained from HLA-B*07:02 restricted RM9 specific T-cell clones sensitive to the R71K mutation are needed to investigate this notion further. 2015 Retrovirology Discussion HIV R71K 96 100 25808313 A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. The four closely-related RM9-Nef peptide-HLAI structures show that similar conformations do not preclude HLAI-specific selection pressures, such as for R71K, that is only observed in the context of HLA-B*07:02. 2015 Retrovirology Discussion HIV R71K 152 156 Nef 29 32 25849352 Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. This occurs rapidly for the NRTI-resistance mutation M184V, which recedes to undetectable levels at a rate of about 50% per year. 2015 PLoS medicine Discussion HIV M184V 53 58 NRTI 28 32 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. All HIV-1 Env trimer preparations currently analyzed by x-ray crystallography contain the I559P change and the SOS alteration that covalently links gp120 and gp41, as well as deletions of part of the gp41 ectodomain, transmembrane region and cytoplasmic tail. 2015 PloS one Discussion HIV I559P 90 95 gp120;gp41;gp41;Env 148;158;200;10 153;162;204;13 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Although Env modifications besides I559P may have contributed to the structure of the soluble gp140 SOSIP.664 glycoprotein observed in the crystal, the isoleucine 559 change is the only alteration within the disordered gp41 segment and thus is a reasonable candidate for the source of this disorder. 2015 PloS one Discussion HIV I559P 35 40 gp140;gp41;Env 94;219;9 99;223;12 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. As the antigenic conformation of the I559P Env is not consistent with that expected for the unliganded state of Env (see above), the I559P change may exert other effects that diminish Env function. 2015 PloS one Discussion HIV I559P;I559P 37;133 42;138 Env;Env;Env 43;112;184 46;115;187 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. As the broad and potent neutralizing antibodies generally bind more efficiently than non-neutralizing antibodies to the wt Env, the epitopes for the potent neutralizing antibodies tended to be preserved on the I559P-containing Envs. 2015 PloS one Discussion HIV I559P 210 215 Env;Env 123;227 126;231 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. At a minimum, the helix-disrupting I559P substitution should impede the formation of the gp41 HR coiled coil. 2015 PloS one Discussion HIV I559P 35 40 gp41 89 93 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Compared with the wt HIV-1BG505 Env, the I559P Env mutant was recognized inefficiently by the polyclonal sera from several HIV-1-infected individuals. 2015 PloS one Discussion HIV I559P 41 46 Env;Env 32;47 35;50 HIV infections 123 137 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Compared with the wt HIV-1BG505 Env, the S375W mutant exhibited greater sensitivity to neutralization by sCD4, but not by the VRC01 CD4BS MAb. 2015 PloS one Discussion HIV S375W 41 46 Env 32 35 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Consistent with an alteration in the gp120-gp41 relationship in the I559P Env, the I559P change in another HIV-1 Env has been reported to result in a loss of sCD4-induced gp120 shedding. 2015 PloS one Discussion HIV I559P;I559P 68;83 73;88 gp120;gp120;gp41;Env;Env 37;171;43;74;113 42;176;47;77;116 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Consistent with this, the PGT151 neutralizing MAb, which recognizes a hybrid gp120-gp41 epitope, bound the I559P Env less efficiently than wt Env. 2015 PloS one Discussion HIV I559P 107 112 gp120;gp41;Env;Env 77;83;113;142 82;87;116;145 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Dramatic reductions in the binding of gp41-directed MAbs were observed for the I559P Env, compared with that of wt Env. 2015 PloS one Discussion HIV I559P 79 84 gp41;Env;Env 38;85;115 42;88;118 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. For some (17b, GE2 JG8, b12, CD4-Ig) but not all of the gp120-directed ligands, the observed decrease in binding to the I559P Env was compensated by the SOS alteration. 2015 PloS one Discussion HIV I559P 120 125 gp120;Env 56;126 61;129 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. How might the I559P change alter the conformation of the membrane-anchored HIV-1BG505 Env? In the crystal structure of the HIV-1BG505 soluble gp140 SOSIP.664 trimer, the gp41 region surrounding isoleucine 559 (residues 548-568) is disordered (Fig 10A). 2015 PloS one Discussion HIV I559P 14 19 gp140;gp41;Env 142;170;86 147;174;89 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. How might the I559P change stabilize soluble gp140 SOS trimers? With the goal of stabilizing an unliganded state of the soluble gp140 Env trimers, the I559P alteration was intended to disrupt the gp41 HR1 helix and thereby destabilize the downstream pre-hairpin intermediate. 2015 PloS one Discussion HIV I559P;I559P 14;151 19;156 gp140;gp140;gp41;Env 45;128;196;134 50;133;200;137 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Importantly, decreased binding of the potent neutralizing antibodies VRC01 and PGT151 is incompatible with a model in which I559P stabilizes the unliganded state of Env. 2015 PloS one Discussion HIV I559P 124 129 Env 165 168 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Importantly, the I559P change induced profound conformational changes within both cytoplasmic-tail truncated (Fig 8) and full-length (Fig 9) Envs. 2015 PloS one Discussion HIV I559P 17 22 Env 141 145 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. In the absence of sCD4, binding of the 17b and A32 MAbs, which prefer the CD4-bound state of gp120, was reduced to background levels by the I559P change. 2015 PloS one Discussion HIV I559P 140 145 gp120 93 98 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Indeed, the spontaneous sampling of the CD4-bound conformation by the gp120 subunit appeared to be decreased for the I559P mutant, relative to that of the wt HIV-1BG505 Env. 2015 PloS one Discussion HIV I559P 117 122 gp120;Env 70;169 75;172 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Instead, we hypothesize that the I559P change disrupts the conformation of the gp41 ectodomain in the soluble gp140 SOSIP.664 trimer and indirectly leads to the formation of the trimer-stabilizing alpha7 helical coiled coil at the trimer axis. 2015 PloS one Discussion HIV I559P 33 38 gp140;gp41 110;79 115;83 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. It is possible that the I559P change results in the disruption of the native gp120-gp41 interface in the context of the membrane-anchored Env and could account for the diverse effects of the I559P change on gp120 and gp41 conformation observed in this and other studies. 2015 PloS one Discussion HIV I559P;I559P 24;191 29;196 gp120;gp120;gp41;gp41;Env 77;207;83;217;138 82;212;87;221;141 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Moreover, although the infectivity of the SOS mutant could be rescued by exposure to the reducing agent DTT, the SOSIP variant containing the I559P change was non-functional regardless of the redox environment. 2015 PloS one Discussion HIV I559P 142 147 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Recognition of the I559P and SOSIP Envs by the PG9 MAb, whose epitope can be influenced by quaternary Env structure, was mildly decreased relative to that of the wt Env. 2015 PloS one Discussion HIV I559P 19 24 Env;Env;Env 35;102;165 39;105;168 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The 35O22 MAb, which recognizes a different gp120-gp41 hybrid epitope, bound more efficiently to the I559P mutant than to wt Env in the presence of sCD4. 2015 PloS one Discussion HIV I559P 101 106 gp120;gp41;Env 44;50;125 49;54;128 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The association of gp120 with the I559P Env trimer was tighter than that observed for wt Env, suggesting that the I559P change alters the relationship among the gp120 and gp41 subunits. 2015 PloS one Discussion HIV I559P;I559P 34;114 39;119 gp120;gp120;gp41;Env;Env 19;161;171;40;89 24;166;175;43;92 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The binding of several ligands (CD4-Ig, VRC01, b12) that recognize a gp120 region near the CD4-binding site was decreased to the I559P mutant, relative to the values seen for wt Env. 2015 PloS one Discussion HIV I559P 129 134 gp120;Env 69;178 74;181 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The CD4-bound conformation is a default state assumed by the HIV-1 gp120 core when the constraints operative in the unliganded state are removed; in the soluble gp140 SOSIP.664 structure, the CD4-bound state of the gp120 core may have resulted from a disruption by I559P of the native gp41-mediated constraints on the unliganded gp120 conformation. 2015 PloS one Discussion HIV I559P 265 270 gp120;gp120;gp120;gp140;gp41 67;215;329;161;285 72;220;334;166;289 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The density in the distal arms of the virion Env trimer that is not explained by the soluble gp140 SOSIP.664 structure (Fig 10B, lower panel) may reflect the shift of the gp120 subunits towards the trimer axis expected as a consequence of the I559P-induced changes. 2015 PloS one Discussion HIV I559P 243 248 gp120;gp140;Env 171;93;45 176;98;48 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The extensive scope of the conformational consequences of the I559P change documented in our study calls into question the latter assumption. 2015 PloS one Discussion HIV I559P 62 67 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P change also reduced the binding of several MAbs directed against the gp120 V3 region, another Env element that is exposed better in the CD4-bound state. 2015 PloS one Discussion HIV I559P 4 9 gp120;Env 79;104 84;107 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P change completely eliminated the ability of the primary HIV-1BG505 Env to mediate syncytium formation and virus entry, as has been previously observed in the context of a laboratory-adapted HIV-1 Env. 2015 PloS one Discussion HIV I559P 4 9 Env;Env 77;206 80;209 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The I559P change was found to stabilize the formation of trimers in the otherwise heterogeneous soluble gp140 Envs. 2015 PloS one Discussion HIV I559P 4 9 gp140;Env 104;110 109;114 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The mildly decreased processing of the I559P mutant relative to that of wt Env is expected to increase the exposure of the Cluster I and Cluster II gp41 epitopes, so the reduced binding of MAbs to these epitopes is all the more striking. 2015 PloS one Discussion HIV I559P 39 44 gp41;Env 148;75 152;78 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The original rationale for the introduction of the I559P change was to destabilize the CD4-bound pre-hairpin intermediate, hopefully predisposing Env to remain in the unliganded state. 2015 PloS one Discussion HIV I559P 51 56 Env 146 149 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The phenotypes observed in this study suggest that the I559P mutant differs from wt Env in the conformations of both the gp120 and gp41 subunits. 2015 PloS one Discussion HIV I559P 55 60 gp120;gp41;Env 121;131;84 126;135;87 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The relationship between structures of Envs with the I559P alteration and conformations of the functional HIV-1 Env spike remains to be determined. 2015 PloS one Discussion HIV I559P 53 58 Env;Env 39;112 43;115 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The S375W Env bound antibodies like 17b and A32, which prefer the CD4-bound conformation, more efficiently than the wt HIV-1BG505 Env, particularly in the presence of sCD4. 2015 PloS one Discussion HIV S375W 4 9 Env;Env 10;130 13;133 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. The success of this strategy in creating more stable soluble trimers in the unliganded conformation relies on two untested assumptions: 1) that the trimeric associations in the unliganded state are tighter than those in the pre-hairpin intermediate, and 2) that the I559P change does not disrupt the unliganded Env conformation more than that of the pre-hairpin intermediate. 2015 PloS one Discussion HIV I559P 266 271 Env 311 314 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. These observations support the conclusion that the I559P change causes significant conformational changes in the gp120 and gp41 subunits within the Env trimer. 2015 PloS one Discussion HIV I559P 51 56 gp120;gp41;Env 113;123;148 118;127;151 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. This observation argues against a model in which the I559P and SOS changes lock Env in an unliganded state. 2015 PloS one Discussion HIV I559P 53 58 Env 80 83 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. This raises the possibility that I559P stabilizes the soluble gp140 SOS trimers by a means other than locking Env in the unliganded state. 2015 PloS one Discussion HIV I559P 33 38 gp140;Env 62;110 67;113 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, during the folding of the soluble gp140 SOSIP.664 Env, the I559P change might disrupt the native gp41 alpha-helical bundle, causing the alpha7 helix and the newly disordered region around isoleucine 559 to collapse towards the trimer axis. 2015 PloS one Discussion HIV I559P 65 70 gp140;gp41;Env 40;103;56 45;107;59 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, the I559P modification alters Env structure in a manner that is independent of the presence of the cytoplasmic tail, some changes in which have been previously shown to affect the structural and functional properties of the Env ectodomain. 2015 PloS one Discussion HIV I559P 10 15 Env;Env 36;230 39;233 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, there currently is no evidence that an HIV-1 Env with an I559P change can mediate membrane fusion or support virus entry. 2015 PloS one Discussion HIV I559P 63 68 Env 51 54 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. Thus, while the I559P mutant resists movement into the CD4-bound state, the I559 change does not guarantee that Env retains an unliganded conformation. 2015 PloS one Discussion HIV I559P 16 21 Env 112 115 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. We investigated the impact of the I559P change, with and without the SOS changes, on the conformation and function of the membrane-anchored Env from HIV-1BG505, the same strain of origin as that of the soluble gp140 SOSIP.664 trimer used in most structural studies. 2015 PloS one Discussion HIV I559P 34 39 gp140;Env 210;140 215;143 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. With a few exceptions (PGT121 and 35O22), the I559P change was associated with decreased recognition by the Env ligands. 2015 PloS one Discussion HIV I559P 46 51 Env 108 111 25849367 Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. With the exception of the mild decrease in recognition by the 4E10 MAb, the relative decrease in anti-gp41 MAb binding to the I559P Env was not compensated by the SOS change. 2015 PloS one Discussion HIV I559P 126 131 gp41;Env 102;132 106;135 25860884 SiRNA-induced mutation in HIV-1 polypurine tract region and its influence on viral fitness. On the nucleic acid side, previous work has demonstrated that introducing G-to-A substitutions at positions -2 and/or -4 in the HIV-1 PPT resulted in enhanced internal cleavage, while a contiguous stretch of 3' terminal Gs has been shown to promote priming of DNA synthesis in both RNA/DNA and DNA/DNA contexts. 2015 PloS one Discussion HIV G2A 74 110 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. Interestingly, we noted that despite the use of a larger viral inoculum, virus-specific T cell responses during PrEP were not observed in monkeys repeatedly exposed to a virus containing the K65R mutation in its reverse transcriptase gene. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 191 195 RT 212 233 25886925 Repeated Vaginal SHIV Challenges in Macaques Receiving Oral or Topical Preexposure Prophylaxis Induce Virus-Specific T-Cell Responses. Our earlier works have shown that the K65R mutation results in reduced replication and viral fitness. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 38 42 25889017 High level of HIV-1 drug resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. In this study, over half the patients with NNRTI resistance harbored the K103N mutation; thus, detection of this sentinel mutation may be useful in expanded surveillance activities for estimating the prevalence of NNRTI resistance. 2015 Virology journal Discussion HIV K103N 73 78 NNRTI;NNRTI 43;214 48;219 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. The E138A mutation selected for by riplivirine/etravirine, must also be a transmitted mutation. 2015 Virology journal Discussion HIV E138A 4 9 25889106 HIV-1 diversity in an antiretroviral treatment naive cohort from Bushbuckridge, Mpumalanga Province, South Africa. While the HIV-1 sequences used in this study are derived from treatment-naive participants from Bushbuckridge, Mpumalanga, the K103N antiretroviral drug resistance mutation was detected. 2015 Virology journal Discussion HIV K103N 127 132 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. Age adjusted full-dose RTV can select M46I, I54V, and V82A in children, as well as L10F, M46L, and Q58E in adults. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV I54V;L10F;M46I;M46L;Q58E;V82A 44;83;38;89;99;54 48;87;42;93;103;58 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. Furthermore, despite failing AZT and LPV/r-containing therapy, T215I and T219N in RT and I50V in PR were not detected by SGS or bulk sequencing during ART for the 2 children ("D and E") who harbored these mutations in their baseline viral populations. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV I50V;T215I;T219N 89;63;73 93;68;78 PR;RT 97;82 99;84 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. M184V was the first mutation selected in the majority of the viral population of the 2 children failing ART with DRMs; the viral load rebounds coincided with the majority of the viral population being replaced with dual-class drug-resistant variants, and notably no AZT-selected mutations were detected during ART. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 0 5 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. Our evidence also points to the triple-class drug-resistant variants detected in "J" to be a result of genetic "hitchhiking" by V108I. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V108I 128 133 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. The baseline PI DRM I50V, TAM revertant K215I, and the TAM K219N of the double mutant Y181C + K219N that were detected in "D, E, and J" may have also been vertically transmitted. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV I50V;K215I;K219N;K219N;Y181C 20;40;59;94;86 24;45;64;99;91 PI 13 15 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. V108I is known to confer modest reductions in NVP/EFV susceptibility in vitro, but its clinical significance is not known. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V108I 0 5 25923117 Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy. We consider the possibility that V108I was selected by NVP for PMTCT because it is not usually found in patients infected with subtype C who were not exposed to this drug. 2015 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V108I 33 38 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. All the previous research indicated that K103N can steadily exist in plasma and PBMC, and quasispecies with K103N could be more possibly to survive in the surrounding with NVP. 2014 AIDS research and therapy Discussion HIV K103N;K103N 41;108 46;113 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Among the K103N, Y181C and G190A, they were not always positively correlated with each other, but may turn to negative correlation with the time of receiving ART. 2014 AIDS research and therapy Discussion HIV G190A;K103N;Y181C 27;10;17 32;15;22 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Among the three NNRTI associated mutations, K103N is one of the most clinically important NNRTI resistance mutations; it causes 20- to 50-fold resistance to most available NNRTIs. 2014 AIDS research and therapy Discussion HIV K103N 44 49 NNRTI;NNRTI;NNRTI 16;90;172 21;95;178 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Among these mutations, K103N Y181C and G190A are the most frequent NNRTI associated drug resistance mutations. 2014 AIDS research and therapy Discussion HIV G190A;K103N;Y181C 39;23;29 44;28;34 NNRTI 67 72 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Based on the results, we estimated that among the three strong NNRTI drug resistance mutations, K103N, Y181C and G190A, there may be some competition process in long-term ART. 2014 AIDS research and therapy Discussion HIV G190A;K103N;Y181C 113;96;103 118;101;108 NNRTI 63 68 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Besides the replication fitness, K103N can persist for a long time in naive patients, over 2 years in a present case report. 2014 AIDS research and therapy Discussion HIV K103N 33 38 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. Here is a question according to the research of Jiong Wang, the reduced fitness for G190A mutants may not explain the increased frequency of G190A variants over time. 2014 AIDS research and therapy Discussion HIV G190A;G190A 84;141 89;146 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In our study, the frequency of K101E had a similar trend with that of G190A in SGA result, and nearly 30% (3/9, 4/16, 7/23, 10/27) K101E emerged with G190A in standard genotyping result. 2014 AIDS research and therapy Discussion HIV G190A;G190A;K101E 70;150;31 75;155;36 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In phenotypic experiments, K103N, Y181C and G190A were defined as the mutations that have almost the same replication fitness with wild type. 2014 AIDS research and therapy Discussion HIV G190A;K103N;Y181C 44;27;34 49;32;39 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. In the initial period of NVP-containing ART, K103N, Y181C and G190A emerged in different rate among quasispecies which K103N and G190A had a higher rate than Y181C. 2014 AIDS research and therapy Discussion HIV G190A;G190A;K103N;K103N;Y181C;Y181C 62;129;45;119;52;158 67;134;50;124;57;163 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. It is true that G190A alone can reduce viral fitness, but another research of Jiong Wang found that the variant with K101E + G190S replicated better in the presence of NNRTIs than in the absence of drug, it indicate that mutation K101E may have some effect on the mutant of Codon 190 to enhance the viral fitness. 2014 AIDS research and therapy Discussion HIV G190A;G190S;K101E;K101E 16;125;117;230 21;130;122;235 NNRTI 168 174 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. K103N also can be found in blood mononuclear cell (PBMC) DNA, with no K103N observed in plasma. 2014 AIDS research and therapy Discussion HIV K103N;K103N 70;0 75;5 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. The rank of fitness among mutant viruses was as follows: wild type (WT) >= Y181C >= K103N >= G190A >= V106A >= P236L >= G190S. 2014 AIDS research and therapy Discussion HIV G190A;G190S;K103N;P236L;V106A;Y181C 93;120;84;111;102;75 98;125;89;116;107;80 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. This may partly explain the question that the increasing of G190A frequency in long-term ART. 2014 AIDS research and therapy Discussion HIV G190A 60 65 25926857 The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy. We found that during the long-term ART treatment, the frequency of K103N, Y181C and G190A were not kept steady, the fact is the frequency of quasispecies with K103N decreased, and could even vanish in SGA sequences, while the proportion of Y181C and G190A could increase from 0% to nearly 100%. 2014 AIDS research and therapy Discussion HIV G190A;G190A;K103N;K103N;Y181C;Y181C 84;250;67;159;74;240 89;255;72;164;79;245 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. One of these 15 patients who was treatment experienced, developed a darunavir RAM at position I84 as a mixture with wild-type (I84I/V), which was not associated with phenotypic resistance to darunavir or other PIs. 2014 AIDS research and therapy Discussion HIV I84I;I84V 127;127 133;133 PI 210 213 25926858 Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. Two patients (one treatment experienced and one treatment naive) developed the M184V RAM while receiving emtricitabine as part of their backbone N[t]RTI that was associated with phenotypic resistance to both lamivudine and emtricitabine. 2014 AIDS research and therapy Discussion HIV M184V 79 84 NRTI 145 152 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. A pooled analysis of sequences submitted to genbank from TDR surveys conducted in SA over 10 years also found K103N followed by Y181C to be the most common TDR mutation in SA [Manasa, 2012]. 2015 Journal of medical virology Discussion HIV K103N;Y181C 110;128 115;133 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. Besides higher rates of TDR, perhaps more importantly and pertinent to the pMTCT program is that the most common TDR mutations detected are those conferring NNRTI resistance, in particular, K103N. 2015 Journal of medical virology Discussion HIV K103N 190 195 NNRTI 157 162 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. Furthermore, using LigAmp to detect minority K103N variants, higher levels of K103N were detected in subtype C compared to A and D [Flys et al., 2006]. 2015 Journal of medical virology Discussion HIV K103N;K103N 78;45 83;50 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. In addition, no K65R mutation associated with resistance to TDF was observed. 2015 Journal of medical virology Discussion HIV K65R 16 20 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. In conclusion, in this resistance study conducted among pMTCT recipients receiving pre-partum AZT, intrapartum sd NVP and post-partum single-dose TDF/FTC, high rates of NVP resistance was detected, in particular K103N. 2015 Journal of medical virology Discussion HIV K103N 212 217 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. The WHO report (2012) indicates that the rate of NNRTI resistance in the African region has increased from 1% in 2003 to 6.4% in 2010 with K103N/S being the most commonly detected mutation [WHO, 2012]. 2015 Journal of medical virology Discussion HIV K103N;K103S 139;139 146;146 NNRTI 49 54 25940687 A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission. Whether this is attributable to poor adherence, higher levels of transmitted resistance, previous exposure to sd NVP or the association of K103N with subtype C, sd NVP, although simple and effective for pMTCT, still remains problematic. 2015 Journal of medical virology Discussion HIV K103N 139 144 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. Furthermore, results from the two mentioned studies found no NNRTI SDRMs, while K103N was identified in 5% of our samples. 2015 PloS one Discussion HIV K103N 80 85 NNRTI 61 66 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. In contrast to these earlier reports that identified a limited number of NRTI mutations (T215D, K219Q and D67G, V75A) with a low overall frequency (4.2% and 5.1%, respectively) in newly infected Iranian cases, we detected a variety of NRTI SDRMs (M41L, D67N, K70R, V75M, F116Y, M184V, L210W, T215Y, and K219E) with a higher overall frequency (10%) in chronically infected IDUs in the city of Sanandaj (Table 2). 2015 PloS one Discussion HIV D67G;D67N;F116Y;K219E;K219Q;K70R;L210W;M184V;M41L;T215D;T215Y;V75A;V75M 106;253;271;303;96;259;285;278;247;89;292;112;265 110;257;276;308;101;263;290;283;251;94;297;116;269 NRTI;NRTI 73;235 77;239 25962088 Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. Moreover, in agreement with previous reports we identified high frequencies of M36I, H69K, L89M/V/I and K20R/T mutations that may be considered as polymorphic signatures within the protease region of CRF35_AD. 2015 PloS one Discussion HIV H69K;K20R;K20T;L89I;L89M;L89V;M36I 85;104;104;91;91;91;79 89;110;110;99;99;99;83 PR 181 189 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Cluster B2 contains sequences with K103N variants as well as wild type. 2015 PloS one Discussion HIV K103N 35 40 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. In our study, one of the notable findings was the presence of a large cluster (B-4) involving 25 patients diagnosed between 2000 and 2011 harboring the T215D resistance mutation. 2015 PloS one Discussion HIV T215D 152 157 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. In this regard, the transmission of T215S mutation within a cluster of newly diagnosed MSM for 2 years has been reported by other authors. 2015 PloS one Discussion HIV T215S 36 41 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. It has been reported that the transmission of M184V has decreased since the 1990s, probably as a consequence of the use of more successful regimens. 2015 PloS one Discussion HIV M184V 46 51 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. It is also interesting to note that in two TC, one of subtype B and another of subtype C, the transmission of the major mutation L90M to PIs was observed in all the viruses of both TC during a period of at least 5 years, suggesting that the fitness of these viruses may play a role in their frequent transmission. 2015 PloS one Discussion HIV L90M 129 133 PI 137 140 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. It is likely that K103N minority species may exist in these wild type infections. 2015 PloS one Discussion HIV K103N 18 23 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. M184V major mutation was detected in 10.1% of the sequences with TDR to NRTIs. 2015 PloS one Discussion HIV M184V 0 5 NRTI 72 77 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. Recently, a large TC involving L90M mutation has been reported among antiretroviral drug-naive MSM of the Swiss HIV Cohort Study with infection dates in 1996-2009, showing the continuous spread of this DRM even after the use of drugs selecting for them had dramatically decreased. 2015 PloS one Discussion HIV L90M 31 35 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. The major mutation K103N was detected in most sequences from newly diagnosed patients included in 2 TC, probably originated from patients failing therapy, with sustained circulation of viruses harboring this mutation for at least 7 years in one of these clusters. 2015 PloS one Discussion HIV K103N 19 24 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. The major mutation L90M was the most common (45.2%) TDR to PIs. 2015 PloS one Discussion HIV L90M 19 23 PI 59 62 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. The most frequent TDR mutations to NRTIs were revertant mutations at 215 position (215rev) (60.7%), followed by M41L (25.3%) and K219Q/R/N/E (24%). 2015 PloS one Discussion HIV K219E;K219N;K219Q;K219R;M41L 129;129;129;129;112 140;140;140;140;116 NRTI 35 40 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. This study argues for early diagnosis and treatment of persons harbouring TDR to avert the genesis of clustered outbreaks driving the spread of drug-resistant subepidemics, including viral lineages with 215 revertants, K103N/S and L90M, that are replicative fit. 2015 PloS one Discussion HIV K103N;K103S;L90M 219;219;231 226;226;235 26010948 Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations. With regard to the TDR to NNRTIs, the most frequent mutations were K103N/S (63%), which is expected, since efavirenz and nevirapine have been part of the recommended first-line HAART regimens in Spain. 2015 PloS one Discussion HIV K103N;K103S 67;67 74;74 NNRTI 26 32 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. It was found that the I84V substitution in HIV-1 PR reduces van der Waals (vdW) interactions with the inhibitors, which might account for the reduced binding affinities of both APV and DRV. 2015 Scientific reports Discussion HIV I84V 22 26 PR 49 51 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. The crystal structure comparison of flap variants (I50V, I54V, and I54M) bound with SQV and variants (G48V, I54V, and I54M) bound with DRV suggested that the change in polar interactions between protease and inhibitors have the best correlation with observed resistance mutations. 2015 Scientific reports Discussion HIV G48V;I50V;I54M;I54M;I54V;I54V 102;51;67;118;57;108 106;55;71;122;61;112 PR 195 203 26012849 Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir. Through comparing the crystal structures of APV and DRV bound WT HIV-1 PR and its MDR variant (L63P, V82T, and I84V) and calculating their corresponding binding thermodynamics, King et al. 2015 Scientific reports Discussion HIV I84V;L63P;V82T 111;95;101 115;99;105 PR 71 73 26020400 Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China. The most common TDR mutations were M46I in PR and Y181C in RT. 2015 Medicine Discussion HIV M46I;Y181C 35;50 39;55 PR;RT 43;59 45;61 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. The most common emergent NNRTI mutations were Y181C/I/D, K103N and V106A/I. 2015 PloS one Discussion HIV K103N;V106A;V106I;Y181C;Y181D;Y181I 57;67;67;46;46;46 62;74;74;55;55;55 NNRTI 25 30 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. The rate of K65R selection was low was, but appeared in approximately one of every three failures, usually with M184V, and more frequently in those treated with 3TC (vs FTC) . 2015 PloS one Discussion HIV K65R;M184V 12;112 16;117 26107265 Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. We observed a significantly higher rate of VF in individuals treated with 3TC instead of FTC, with a significantly higher rate of selection of M184V as well. 2015 PloS one Discussion HIV M184V 143 148 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. Finally, the K77Q (adjacent to HR1) and H132Y (in domain HR2) mutations, both in gp41, reduced the activity of T20, the FDA-approved gp41 fusion inhibitor. 2015 PloS one Discussion HIV H132Y;K77Q 40;13 45;17 gp41;gp41 81;133 85;137 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. The mutation Q280H on the tip of the V3 loop explains the interaction of LA with the V3 loop and this mutation was also observed with previously reported polyanionic compounds. 2015 PloS one Discussion HIV Q280H 13 18 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. The R389T substitution in the C5 region is situated adjacent to the V4 loop and was described previously as another important sequence involved in CD4 and mAb b12 binding. 2015 PloS one Discussion HIV R389T 4 9 26132818 The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. We found that LA is able to interfere with the CD4/gp120 binding as the V170N mutation occurred in a sequence of the C2 region, which is part of the CD4-induced epitope. 2015 PloS one Discussion HIV V170N 72 77 gp120 51 56 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. A study of CRF01_AE HIV-infected Cambodian patients found the Q151M mutation to be associated with stavudine-use. 2016 Journal of medical virology Discussion HIV Q151M 62 67 HIV infections 20 32 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Although Q151M was found in two patients with the highest didanosine FC differences, our study could not directly support the possible link between Q151M and the highly discordant didanosine FC values. 2016 Journal of medical virology Discussion HIV Q151M;Q151M 9;148 14;153 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. An outlier existed in each of the subtype groups with the associated sample being the only one for each subtype to harbour the multiple NRTI drug resistance mutation Q151M. 2016 Journal of medical virology Discussion HIV Q151M 166 171 NRTI 136 140 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Because resistance algorithms can be affected by specific mutation combinations, it is possible that the combination of Q151M and TAMs found in these two samples may have partly influence the predicted resistance calls derived from the algorithm. 2016 Journal of medical virology Discussion HIV Q151M 120 125 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. From the Bland-Altman plot, the sample that showed the largest difference between the predicted virtual phenotype FC value and the laboratory-based phenotype FC value for didanosine, i.e the outlier sample for each subtype, was the only sample for that subtype group to contain the Q151M mutation. 2016 Journal of medical virology Discussion HIV Q151M 282 287 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. On the contrary, the presence of Q151M was not associated with any predictors in subtype B HIV-infected patients from the Swiss HIV Cohort Study. 2016 Journal of medical virology Discussion HIV Q151M 33 38 HIV infections 91 103 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Other RT RAMs found in the CRF01_AE sample were thymidine analogue-associated mutations (TAMs) which included D67N, K70R and K219Q. 2016 Journal of medical virology Discussion HIV D67N;K219Q;K70R 110;125;116 114;130;120 RT 6 8 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Our CRF01_AE patient harbouring the Q151M mutation was treated with didanosine, zidovudine and boosted lopinavir at the time of sample collection. 2016 Journal of medical virology Discussion HIV Q151M 36 41 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Q151M is the most important mutation in this complex as other mutations alone may not cause multiple drug resistance. 2016 Journal of medical virology Discussion HIV Q151M 0 5 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. That is, only one CRF01_AE sample and one subtype B sample analysed in our study, both of which showed the biggest differences in didanosine FC values, were found to have the Q151M RAM. 2016 Journal of medical virology Discussion HIV Q151M 175 180 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. The presence of Q151M and TAMs in these two samples indicate multiple NRTI drug resistance, which supports our "resistant" interpretation results for didanosine. 2016 Journal of medical virology Discussion HIV Q151M 16 21 NRTI 70 74 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. The Q151M complex, consisting of Q151M, A62V, V75I, F77L and F116Y, is associated with resistance to all approved NRTIs except for tenofovir. 2016 Journal of medical virology Discussion HIV A62V;F116Y;F77L;Q151M;Q151M;V75I 40;61;52;4;33;46 44;66;56;9;38;50 NRTI 114 119 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. The subtype B sample contained all mutations in the Q151M complex while the CRF01_AE sample lacked the F77L mutation. 2016 Journal of medical virology Discussion HIV F77L;Q151M 103;52 107;57 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Therefore we could not confirm the possible association between Q151M and stavudine exposure using our sample. 2016 Journal of medical virology Discussion HIV Q151M 64 69 26147742 Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals. Two TAMs were also present in the subtype B sample (D67N and K219E). 2016 Journal of medical virology Discussion HIV D67N;K219E 52;61 57;66 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. Although viral genotyping was not performed at VF, the presence of another mutation at time of switch to second line therapy (K103N) was significantly associated (p=0.039) with poor ART adherence. 2015 The open AIDS journal Discussion HIV K103N 126 131 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. In another study, 108 Ugandan treatment-experienced children whose virus at baseline contained the RT mutation M184V were switched to PI-containing regimens. 2015 The open AIDS journal Discussion HIV M184V 111 116 PI;RT 134;99 136;101 26157536 Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens. This patient's virus had the major PI mutations M46L, V82A and L90M at baseline, and the I54L mutation emerged during therapy. 2015 The open AIDS journal Discussion HIV I54L;L90M;M46L;V82A 89;63;48;54 93;67;52;58 PI 35 37 26161559 Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique. The most frequent reverse transcriptase mutations were Y181C, K103N and G190A. 2015 PloS one Discussion HIV G190A;K103N;Y181C 72;62;55 77;67;60 RT 18 39 26241860 The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon. Indeed, it was not possible to just split the tree in two C181 and Y181 subpopulations, even if hypothesizing unlikely transmissions of strains with acquired mutations for the few T strains harbouring this Y181C mutation. 2015 PLoS pathogens Discussion HIV Y181C 206 211 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. Instead, we observed both retention of the original deleterious mutations (K422R and A598T) and the acquisition of additional mutations throughout the protein. 2015 Retrovirology Discussion HIV A598T;K422R 85;75 90;81 26248668 Determinants in HIV-2 Env and tetherin required for functional interaction. Interestingly, we found that the minimal changes required to restore anti-tetherin activity mapped to the cytoplasmic domain of the protein, specifically K796R, and D830G. 2015 Retrovirology Discussion HIV D830G;K796R 165;154 170;159 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. Although K65R has been previously shown to rapidly revert to wild-type post-infection, we document persistence of K65R in all infected animals, likely the result of introducing two mutations (AAA) in the K65 codon versus the single nucleotide mutation often found in naturally emerging K65R mutations. 2015 Retrovirology Discussion HIV K65R;K65R;K65R 9;114;286 13;118;290 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. Both the modest 5-fold resistance to TFV conferred by K65R and the high levels of TFV-DP in vaginal lymphocytes likely explain the observed protection in this model. 2015 Retrovirology Discussion HIV K65R 54 58 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. Here, we show in a macaque model that TFV delivered by vaginal gel maintained protection against a SHIV isolate with the K65R mutation that shares the same TFV resistance and replicative fitness profile with HIV-1K65R. 2015 Retrovirology Discussion HIV K65R;K65R 213;121 217;125 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. HIV treatment programs with regimens containing either TDF or d4T have the potential to enrich for TFV-resistant HIV-1 containing the K65R mutation among persons experiencing virologic failure on these regimen, thus raising questions about efficacy of topical TFV products for prevention among uninfected persons exposed to such viruses. 2015 Retrovirology Discussion HIV K65R 134 138 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. The low in vivo transmissibility of SHIV162P3K65R at virus doses that efficiently infect macaques with wild-type SHIV162P3 is consistent with the high fitness cost conferred by K65R and lower transmission rate observed previously. 2015 Retrovirology Discussion HIV K65R 177 181 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. These findings further support the use of this K65R isolate as a tool for executing TFV resistant transmission and prevention studies under well-controlled conditions. 2015 Retrovirology Discussion HIV K65R 47 51 26253002 Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques. We also note that while our results address the efficacy against low-level TFV resistance mediated by K65R, our findings may have broader implications on mutant viruses with a similar level of TFV resistance conferred by other mutations as seen clinically with multiple thymidine analog mutations. 2015 Retrovirology Discussion HIV K65R 102 106 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. Additional studies would be needed to better assess the frequency of co-emergent E138K and M184I mutations in ARV-naive patients treated with etravirine. 2016 Antiviral therapy Discussion HIV E138K;M184I 81;91 86;96 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. Existing data raise concern that the E138K and M184I mutations can interact to increase viral replication capacity, offsetting the decreased viral fitness usually associated with the M184I/V mutations. 2016 Antiviral therapy Discussion HIV E138K;M184I;M184I;M184V 37;47;183;183 42;52;190;190 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. In the DUET studies, however, participants all had at least one baseline NNRTI mutation and treatment-emergent mutations at position E138 in the reverse transcriptase enzyme were also observed, in addition to the more frequent V179F/I and Y181C mutations. 2016 Antiviral therapy Discussion HIV V179F;V179I;Y181C 227;227;239 234;234;244 RT;NNRTI 145;73 166;78 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. The E138K mutation contributes phenotypic resistance to ETR and rilpivirine, and has most often been reported in clinical trials of rilpivirine, commonly accompanied by the M184I mutation, as was seen in 1 of our participants. 2016 Antiviral therapy Discussion HIV E138K;M184I 4;173 9;178 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. The occurrence of RAMs in some of the patients who experienced virologic failure, and in particular the co-emergence of E138K and M184I mutations in 1 patient, does raise concern about the potential for evolution of resistance if patients experience treatment failure with this regimen. 2016 Antiviral therapy Discussion HIV E138K;M184I 120;130 125;135 26263403 Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results. Three participants who experienced virologic failure with HIV-1 RNA > 500 copies/mL at the time of failure had RAMs, 1 of whom had multiple RAMs, including E138K and M184I, none of which were present on the screening genotype at baseline. 2016 Antiviral therapy Discussion HIV E138K;M184I 156;166 161;171 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. By contrast, the CRF17_BF cluster has been characterized by HIV-1 strains resistant to both first and second NNRTIs generations, due to the presence of the RT mutations K101E and E138K. 2015 PloS one Discussion HIV E138K;K101E 179;169 184;174 NNRTI;RT 109;156 115;158 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. In particular, in the setting of the C cluster, all the 27 viruses carried key mutations required for both CCR5 and CXCR4 binding, such as the E25D and H13R. 2015 PloS one Discussion HIV E25D;H13R 143;152 147;156 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. Indeed, all patients involved in the HIV-1 C cluster carried HIV-1 strains with the K103Q, an atypical and rarely found mutation present in a position critical for Nevirapine and Efavirenz efficacy. 2015 PloS one Discussion HIV K103Q 84 89 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. The analysis of the V3 region of patients involved in the CRF17_BF cluster revealed, instead, the existence of two distinct viral species, both R5 by the Geno2Pheno algorithm, the first one characterized by the CCR5 key mutations T22A and E25D, and the other one by the CXCR4 associated mutations E25Q and Q32K. 2015 PloS one Discussion HIV E25D;E25Q;Q32K;T22A 239;297;306;230 243;301;310;234 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. This mutation is codified by the CAA (Q) codon that decreases the genetic barrier to select the NNRTI drug resistance K103H mutation. 2015 PloS one Discussion HIV K103H 118 123 NNRTI 96 101 26270824 Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy. Thus, even if this mutation is already known by the literature to not confer NNRTIs resistance, we can hypothesize that this atypical RT mutation can represent a revertant for K103H. 2015 PloS one Discussion HIV K103H 176 181 NNRTI;RT 77;134 83;136 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Importantly, phenotypic and/or clinical evidence indicate that D30N mutation confers high-level resistance to nelfinavir; L90M imparts resistance to nelfinavir, sequinavir, indinavir, and lopinavir; while M46I confers resistance to indinavir, lopinavir, fosamprenavir and nelfinavir. 2015 AIDS research and therapy Discussion HIV D30N;L90M;M46I 63;122;205 67;126;209 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. In addition, our results corroborate previous studies showing K20I/M/R, L10I/V, I13V, and L63P minor mutations among HIV infected treatment-naive individuals in Morocco. 2015 AIDS research and therapy Discussion HIV I13V;K20I;K20M;K20R;L10I;L10V;L63P 80;62;62;62;72;72;90 84;70;70;70;78;78;94 HIV infections 117 129 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. In the current study, major PI mutations were detected only in IDUs with the antiretroviral treatment-experienced (L90M, D30N and M46I) individuals having higher rates than -naive (D30N) individuals. 2015 AIDS research and therapy Discussion HIV D30N;D30N;L90M;M46I 121;181;115;130 125;185;119;134 PI 28 30 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. It is important to emphasize that three of the individuals with major mutations concurrently harboured G48E, K20I, K20R and T74S minor mutations. 2015 AIDS research and therapy Discussion HIV G48E;K20I;K20R;T74S 103;109;115;124 107;113;119;128 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Likewise, our results are similar to previous studies showing presence of L90M, D30N, and M46I mutations among antiretroviral-naive IDUs in Rio de Janeiro, Brazil. 2015 AIDS research and therapy Discussion HIV D30N;L90M;M46I 80;74;90 84;78;94 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Most importantly, major mutations, D30N and M46I co-existed with minor mutations, G48E, K20I and T74S, suggesting that these mutations mediate evolution of major drug resistance. 2015 AIDS research and therapy Discussion HIV D30N;G48E;K20I;M46I;T74S 35;82;88;44;97 39;86;92;48;101 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Our findings of L90M, D30N, and M46I mutations, are partly consistent with previous studies reporting on the presence of major PI mutations D30N and M46I in ART-naive sex workers, a most-at-risk-population from Nairobi, Kenya. 2015 AIDS research and therapy Discussion HIV D30N;D30N;L90M;M46I;M46I 22;140;16;32;149 26;144;20;36;153 PI 127 129 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. Our results are also, in part, consistent with previous studies in Canada showing D30N, M46I, and L90M PI resistance mutations among individuals reporting a history of injection drug use. 2015 AIDS research and therapy Discussion HIV D30N;L90M;M46I 82;98;88 86;102;92 PI 103 105 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. The detection of A71T, G48E/R, I13V, K20I/R, L10I/V, L33F, L63P, T74S, V11I, and V32L minor mutations in this study is, in part, consistent with previous studies that reported K20R, L10I/V, L33F/I, and L63P minor mutations among HIV-positive women attending antenatal clinics in a large HIV treatment study in western Kenya. 2015 AIDS research and therapy Discussion HIV A71T;G48E;G48R;I13V;K20I;K20R;K20R;L10I;L10I;L10V;L10V;L33F;L33F;L33I;L63P;L63P;T74S;V11I;V32L 17;23;23;31;37;37;176;45;182;45;182;53;190;190;59;202;65;71;81 21;29;29;35;43;43;180;51;188;51;188;57;196;196;63;206;69;75;85 26279669 HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users. This is not surprising because G48E inhibits as K20I, K20R and T74S enhance viral replication. 2015 AIDS research and therapy Discussion HIV G48E;K20I;K20R;T74S 31;48;54;63 35;52;58;67 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. As mutations at codon 140 play a key role in restoring the fitness of Q148 mutants, their occurrence can also influence the emergence of Q148H/R/K, thus explaining the reduced prevalence of Q148 mutants observed in non-B subtypes. 2015 The Journal of antimicrobial chemotherapy Discussion HIV Q148H;Q148K;Q148R 137;137;137 146;146;146 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Consistent with available data, there was a strong preferential association of N155H with E92Q, Y143H/R/C with T97A, and G140S/A with Q148H/R/K. 2015 The Journal of antimicrobial chemotherapy Discussion HIV E92Q;G140A;G140S;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143H;Y143R 90;121;121;79;134;134;134;111;96;96;96 94;128;128;84;143;143;143;115;105;105;105 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Indeed, the N155H and Q148H/R/K pathways have been shown to sequentially emerge in separate genomes within a given individual over time. 2015 The Journal of antimicrobial chemotherapy Discussion HIV N155H;Q148H;Q148K;Q148R 12;22;22;22 17;31;31;31 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Of these three mutually antagonistic genotypic patterns, Q148H/R/K and G140S/A were significantly more prevalent in subtype B than in non-B clades, occurring only in three subjects (with subtype C and subtype G). 2015 The Journal of antimicrobial chemotherapy Discussion HIV G140A;G140S;Q148H;Q148K;Q148R 71;71;57;57;57 78;78;66;66;66 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Q148H/R/K mutations were present in 17% of raltegravir-experienced patients and ~16% of the raltegravir-experienced patients were classified as having intermediate- to high-level resistance to dolutegravir. 2015 The Journal of antimicrobial chemotherapy Discussion HIV Q148H;Q148K;Q148R 0;0;0 9;9;9 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Small studies previously proposed a higher genetic barrier for G140S and G140C in subtypes C, CRF01 and CRF02 and more recently a large study of INI-experienced patients identified more Q148 mutations in subtype B versus non-B subtypes. 2015 The Journal of antimicrobial chemotherapy Discussion HIV G140C;G140S 73;63 78;68 IN 145 148 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. Strikingly, Q148H and G140S occurred in 13% and 16% of subtype B sequences, respectively, but were absent from all non-B clades analysed. 2015 The Journal of antimicrobial chemotherapy Discussion HIV G140S;Q148H 22;12 27;17 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. The analysis also identified novel mutations as significantly associated with raltegravir selective pressure:K159Q/R, I161L/M/N/T/V and E170AG. 2015 The Journal of antimicrobial chemotherapy Discussion HIV E170A;E170G;I161L;I161M;I161N;I161T;I161V;K159Q;K159R 136;136;118;118;118;118;118;109;109 142;142;131;131;131;131;131;116;116 26311843 Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. The three major recognized pathways of genotypic resistance to raltegravir (N155H, Q148H/R/K and Y143R/C/H) were represented in the raltegravir-experienced population. 2015 The Journal of antimicrobial chemotherapy Discussion HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 76;83;83;83;97;97;97 81;92;92;92;106;106;106 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. 0.727 for T215Rev, Table 1); however, precision was low for SDRMs with low prevalence in treatment-failing patients: N83D has a high transmission ratio (0.165) but was only found in one drug-naive and five treatment-failing patients, with large CI. 2015 AIDS (London, England) Discussion HIV N83D 117 121 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. Our results are consistent with other studies: M184I/V has been shown to have low persistence after transmission to drug-naive patients; G190A has been shown to have high persistence. 2015 AIDS (London, England) Discussion HIV G190A;M184I;M184V 137;47;47 142;54;54 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. T215Rev and T215Y/F are above and below the regression line respectively, supporting our model, as T215Y/F has a fitness cost in absence of drug and reverts after transmission into one of the T215Rev mutants with less onward transmission of T215Y/F between drug-naive patients. 2015 AIDS (London, England) Discussion HIV T215F;T215F;T215F;T215Y;T215Y;T215Y 12;99;241;12;99;241 19;106;248;19;106;248 26355575 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. We show here that D30N, N88D/S and L90 M also have high transmissibility and that other SDRMs have higher (M41L, T215Rev and K219E/N/Q/R for NRTIs and K101E/P for the NNRTIs) or lower transmissibility (K70E/R, L74I/V, and T215Y/F for NRTIs; Y181C/I/V for NNRTIs and I84 V and I54A/L/M/S/T/V for protease inhibitors) compared with other mutations of the same drug class. 2015 AIDS (London, England) Discussion HIV D30N;I54A;I54L;I54M;I54S;I54T;I54V;I84V;K101E;K101P;K219E;K219N;K219Q;K219R;K70E;K70R;L74I;L74V;L90M;M41L;N88D;N88S;T215F;T215Y;Y181C;Y181I;Y181V 18;276;276;276;276;276;276;266;151;151;125;125;125;125;202;202;210;210;35;107;24;24;222;222;241;241;241 22;290;290;290;290;290;290;271;158;158;136;136;136;136;208;208;216;216;40;111;30;30;229;229;250;250;250 PR;NNRTI;NNRTI;NRTI;NRTI 295;167;255;141;234 303;173;261;146;239 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. As seen with K103N in individual 1, and M184V in individuals 2 and 4, once the resistant strains were selected, they persisted as minority populations even after their corresponding ARVs were withdrawn, to re-emerge soon after their selective antiretroviral drugs were readministered. 2015 PloS one Discussion HIV K103N;M184V 13;40 18;45 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Here we present evidence for M184V and K103N, which are key resistance mutations and frequently observed in both treated and newly diagnosed individuals. 2015 PloS one Discussion HIV K103N;M184V 39;29 44;34 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. However, in some cases the phylogenetic analysis has clarified the outgrowth of minority-level K103N, suggesting that pre-existing K103N variants may have affected subsequent treatment failure. 2015 PloS one Discussion HIV K103N;K103N 95;131 100;136 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Likewise for individual 4, M184V was detected at 2 of 13 time points (day 616-2042) (S5 Table). 2015 PloS one Discussion HIV M184V 27 32 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Notably, the detection of minority levels of resistant variants was not continuous but sporadic for mutations, such as K103N in individual 1 where minority K103N was detected only 3 times among 21 samples (14.3%) between day 311 and 1369, suggesting that the minority K103N population existed around the threshold level of AS-PCR which is 1% of the total population. 2015 PloS one Discussion HIV K103N;K103N;K103N 119;156;268 124;161;273 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Phylogenetic analysis showed that K103N, which was detected as minority by AS-PCR before treatment with EFV, became the major population after the regimen included EFV was initiated. 2015 PloS one Discussion HIV K103N 34 39 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Similar findings were observed for individual 2, in which M184V was detected in 8 of 12 time points (day 1393-2373) and T215Y in 1 of 3 (day 565-793). 2015 PloS one Discussion HIV M184V;T215Y 58;120 63;125 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. Therefore, the detection of minority M184V in individual 4 and minor-M41L in individual 3 might reflect decay kinetics rather than persistence. 2015 PloS one Discussion HIV M184V;M41L 37;69 42;73 26360259 Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. This result demonstrated that minor-K103N may have been a factor in treatment failure after switching to the EFV-containing regimen. 2015 PloS one Discussion HIV K103N 36 41 26397743 Conformational variation of an extreme drug resistant mutant of HIV protease. We performed 10ns MD simulations to analyze the dynamics of PR20 and wild type PR starting from the closed conformation for both the active protein and a commonly used inactive model system (D25N mutation). 2015 Journal of molecular graphics & modelling Discussion HIV D25N 191 196 PR;PR 60;79 62;81 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. assessed rifampicin fitness by transcriptional efficiency (rather than growth) and showed that the S450L mutation has half the transcriptional efficiency of WT rpoB, which is likely to impart fitness consequences if not compensated. 2015 PLoS medicine Discussion HIV S450L 99 104 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. However, as shown in our study and in several others, rpoB S450L was the most likely RRDR polymorphism to evolve putative compensatory mutations, which calls into question the low fitness cost of S450L in vivo. 2015 PLoS medicine Discussion HIV S450L;S450L 59;196 64;201 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. Laboratory-derived strains carrying the S450L were previously shown to have relatively high fitness in in vitro growth assays, supporting the hypothesis that high prevalence of the S450L mutation among clinical strains was due to it imparting few fitness consequences. 2015 PLoS medicine Discussion HIV S450L;S450L 40;181 45;186 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. The most commonly observed genotypic rifampicin resistance mutation among our sequenced strains was rpoB S450L (often referred to as S531L using the Escherichia coli codon numbering scheme), which is known to be the most prevalent RRDR mutation. 2015 PLoS medicine Discussion HIV S450L;S531L 105;133 110;138 26418737 Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. While the majority of the previously described rifampicin compensatory mutations had an evolutionary pattern consistent with this role, four polymorphisms previously associated with rifampicin compensation (rpoB I491F, rpoC G594E and N826K, and rpoA E319K) were not observed to evolve concurrently or subsequent to genotypic rifampicin resistance (S4 Table). 2015 PLoS medicine Discussion HIV E319K;G594E;I491F;N826K 250;224;212;234 255;229;217;239 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Another study from Delobel et al., who compared the performance of 454 UDS and ASPCR to detect the K103N resistance mutation, also found ASPCR to be more sensitive. 2015 PloS one Discussion HIV K103N 99 104 26469189 Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission. Resistance mutations present in low frequencies such as the AZT resistance mutations, in particular the minor mutation T215Y/F that occurred at low proportions of <1% due to the higher genetic barrier of two amino acid substitutions, were therefore underestimated by UDS as compared to ASPCR (6 vs 10). 2015 PloS one Discussion HIV T215F;T215Y 119;119 126;126 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Among the NNRTIs mutations, K103N, V106M, and G190A conferring resistance to EFV and NVP; EFV, NVP and ETR; and EFV and NVP, respectively were observed in 2 and 1 patient each similar to recent data from various African countries. 2015 PloS one Discussion HIV G190A;K103N;V106M 46;28;35 51;33;40 NNRTI 10 16 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Despite the extensive use of thymidine analogues like AZT or D4T in Ethiopia and unlike previous similar studies, TAMs characterized by the mutations M41L, L210W, T215Y (TAM-path 1) and D67N, K70R, T215F, K219Q/E (TAM-path 2) were lacking in the current study indicating a recent period of virological failure. 2015 PloS one Discussion HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 186;205;205;192;156;150;198;163 190;212;212;196;161;154;203;168 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. Four out of six patients failed as a result of M184V and NNRTIs mutation. 2015 PloS one Discussion HIV M184V 47 52 NNRTI 57 63 26512902 Low Incidence of HIV-1C Acquired Drug Resistance 10 Years after Roll-Out of Antiretroviral Therapy in Ethiopia: A Prospective Cohort Study. The K65R known to be selected faster in subtype C was observed in one patient who has been taking 3TC, D4T and EFV. 2015 PloS one Discussion HIV K65R 4 8 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. One breast-fed infant had K65R detected at week 4, in the context of maternal treatment with 21 days of TDF/FTC. 2014 Journal of AIDS & clinical research Discussion HIV K65R 26 30 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. One infant had a new K70R mutation, concordant with a maternal K70R mutation and in the context of antenatal and infant ZDV. 2014 Journal of AIDS & clinical research Discussion HIV K70R;K70R 21;63 25;67 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. Presumably, this infant acquired a new K65R mutation after brief intrapartum and/or breastfeeding exposure to maternal study treatment. 2014 Journal of AIDS & clinical research Discussion HIV K65R 39 43 26525108 Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207. These findings suggest that the infant K70R mutation may have been of maternal origin, possibly related to antenatal ZDV exposure. 2014 Journal of AIDS & clinical research Discussion HIV K70R 39 43 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. Although our patients did not use the second-generation NNRTI, etravirine (ETR), cross-resistance to this drug was significant in regimens of second failure (31.9%), associated with G190S and M230L mutations. 2015 BioMed research international Discussion HIV G190S;M230L 182;192 187;197 NNRTI 56 61 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. In our study, L76V PI-associated mutation was the only one that differed significantly in prevalence between B and non-B subtypes, being more frequent in the latter. 2015 BioMed research international Discussion HIV L76V 14 18 PI 19 21 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. In PR, mutations M46I/L, I54V, L76V, V82A, I84V, and L90M were associated with PI/r resistance in multifailed patients. 2015 BioMed research international Discussion HIV I54V;I84V;L76V;L90M;M46I;M46L;V82A 25;43;31;53;17;17;37 29;47;35;57;23;23;41 PI;PR 79;3 81;5 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. L63P and A71T were associated with subtype B, whereas L10V, K20R, M36I, F53L, and L89M were linked to non-B subtypes. 2015 BioMed research international Discussion HIV A71T;F53L;K20R;L10V;L89M;M36I;L63P 9;72;60;54;82;66;0 13;76;64;58;86;70;4 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. M230L alone produces moderate resistance to ETR, while G190S requires at least another mutation of equal weight to establish resistance. 2015 BioMed research international Discussion HIV G190S;M230L 55;0 60;5 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. On the other hand, in multifailed individuals, seven major PI mutations associated with resistance were documented: M46I, V82A, I54V, L90M, I84V, M46L, and L76V. 2015 BioMed research international Discussion HIV I54V;I84V;L76V;L90M;M46I;M46L;V82A 128;140;156;134;116;146;122 132;144;160;138;120;150;126 PI 59 61 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. Previous PI-based treatments might have contributed to the emergence of PI major mutations M46I, V82A, L90M, I84V, M46L, and L76V, associated with resistance to APV/r. 2015 BioMed research international Discussion HIV I84V;L76V;L90M;M46I;M46L;V82A 109;125;103;91;115;97 113;129;107;95;119;101 PI;PI 9;72 11;74 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. Resistance to NRTIs in multifailed patients was related to the presence of the TAMs M41L, D67N, L210W, and K219Q. 2015 BioMed research international Discussion HIV D67N;K219Q;L210W;M41L 90;107;96;84 94;112;101;88 NRTI 14 19 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. The high prevalence of the K103N (40.6%) and the P225H (10.6%) mutations detected was associated with high-level resistance to efavirenz and nevirapine in the first antiretroviral treatment, as was expected. 2015 BioMed research international Discussion HIV K103N;P225H 27;49 32;54 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. The resistance-associated mutations profile showed a high prevalence of M184V, TAMs, and K103N in RT. 2015 BioMed research international Discussion HIV K103N;M184V 89;72 94;77 RT 98 100 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. The selection of the I84V mutation is common to all PIs, including those with the highest genetic barrier, DRV/r and TPV/r. 2015 BioMed research international Discussion HIV I84V 21 25 PI 52 55 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. There was a relevant emergence of M184V and TAMs, related to NRTIs, and of K103N, related to the NNRTIs. 2015 BioMed research international Discussion HIV K103N;M184V 75;34 80;39 NNRTI;NRTI 97;61 103;66 26543866 The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. We think, however, that the Q58E mutation, together with other accessory mutations, L10V, L33F, and K43T, may have contributed to the higher prevalence of TPV/r resistance in relation to DRV/r observed in our study. 2015 BioMed research international Discussion HIV K43T;L10V;L33F;Q58E 100;84;90;28 104;88;94;32 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. However, even when excluding M184V from the analysis, the lack of correlation between NRTI PDR and ADR mutation frequency remained. 2015 PloS one Discussion HIV M184V 29 34 NRTI 86 90 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Indeed, other NRTI DR mutations as M41L, D67N, K70R, L210W, and T215Y/F. 2015 PloS one Discussion HIV D67N;K70R;L210W;M41L;T215F;T215Y 41;47;53;35;64;64 45;51;58;39;71;71 NRTI 14 18 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Indeed, we observed two clusters containing viruses with ADR and PDR in which the virus with ADR possessed M184V and the virus with PDR did not, suggesting reversion upon transmission. 2015 PloS one Discussion HIV M184V 107 112 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. The fact that this correlation was not evident for NRTI could be due to the frequent reversion of mutations with high fitness costs such as M184V upon transmission, while PI and NNRTI mutations replacement rates are low. 2015 PloS one Discussion HIV M184V 140 145 NNRTI;NRTI;PI 178;51;171 183;55;173 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. This result strongly supports recent observations evidencing the common and stable transmission of some TDR mutations including PR L90M and RT K103N, and T215 revertants. 2015 PloS one Discussion HIV K103N;L90M 143;131 148;135 PR;RT 128;140 130;142 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. Transmission of RT K103N was observed in two cases, while transmission of PR M46L and RT T215 revertants was observed in another case. 2015 PloS one Discussion HIV K103N;M46L 19;77 24;81 PR;RT;RT 74;16;86 76;18;88 26558396 HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. We observed a significant decrease in the frequency of NRTI PDR mutations (D67N, K70R, M184V, T215Y) and an increase in the frequency of K103N (Fig 4), consistent with a long-term decrease in NRTI PDR and increase in NNRTI PDR in Honduras since the beginning of the national ART programme. 2015 PloS one Discussion HIV D67N;K103N;K70R;M184V;T215Y 75;137;81;87;94 79;142;85;92;99 NNRTI;NRTI;NRTI 217;55;192 222;59;196 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. As M46I mutation has also been observed in few PI naive patients we could have slightly overestimated the selection of this mutation in our study as genotyping was not performed before the start of second line therapy. 2015 BMC infectious diseases Discussion HIV M46I 3 7 PI 47 49 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. M46I was the commonest PI mutation observed in our study which reduces susceptibility to all PI except darunavir. 2015 BMC infectious diseases Discussion HIV M46I 0 4 PI;PI 23;93 25;95 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. N88S was the second most common PI mutation in our study which is associated with resistance to ATV/r and nelfinavir. 2015 BMC infectious diseases Discussion HIV N88S 0 4 PI 32 34 26572102 Outcome of patients on second line antiretroviral therapy under programmatic condition in India. Only two patients had I84V mutation which confers broad spectrum resistance to all PIs and low level resistance to DRV. 2015 BMC infectious diseases Discussion HIV I84V 22 26 PI 83 86 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. A study detected that multiple mutations (K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y) significantly increased NVP resistance. 2015 Virology journal Discussion HIV H221Y;K103N;Y181C;H221Y;K103N;K103N;Y181C 54;42;48;80;61;74;67 59;47;53;85;66;79;72 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. According to the mutation patterns that emerged in plasma, i.e., Y181C followed by H221Y. 2015 Virology journal Discussion HIV H221Y;Y181C 83;65 88;70 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Adding Y181C to T215Y/K103N lowered the IC50 of AZT to insignificance. 2015 Virology journal Discussion HIV K103N;T215Y;Y181C 22;16;7 27;21;12 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Additionally, Y181C did not modify resistance of T215Y/V179E to d4T and led to an increase in the mean IC50 value from 240.77 +- 34.68 nM for T215Y/V179E to 622.10 +- 82.10 nM for the triple-mutation with respect to 3TC. 2015 Virology journal Discussion HIV T215Y;T215Y;V179E;V179E;Y181C 49;142;55;148;14 54;147;60;153;19 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Alone H221Y has minimal detectable effects on NNRTI susceptibility. 2015 Virology journal Discussion HIV H221Y 6 11 NNRTI 46 51 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. At the end of the current investigation, we found that the mutation at 179 exited stably with V179E, but not initially with V179D. 2015 Virology journal Discussion HIV V179D;V179E 124;94 129;99 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. But resistance to EFV of T215Y/V179E is not significant in our study. 2015 Virology journal Discussion HIV T215Y;V179E 25;31 30;36 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Classical key mutations (TAMs, M184V, K103N and so on) recruited in HIV drug resistance database are responsible for either drug-specific resistance or cross resistance; and along with these, viral strains demonstrate non-canonical changes in treated patients whose contribution to the phenotype is unknown. 2015 Virology journal Discussion HIV K103N;M184V 38;31 43;36 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Contribution to resistance for H221Y was insignificant compared with Y181C. 2015 Virology journal Discussion HIV H221Y;Y181C 31;69 36;74 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Dramatically, Y181C and H221Y expressed synergism in a T215Y/K103N background of. 2015 Virology journal Discussion HIV H221Y;K103N;T215Y;Y181C 24;61;55;14 29;66;60;19 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. For EFV, only Y181C increased the IC50 in a T215Y/V179E background. 2015 Virology journal Discussion HIV T215Y;V179E;Y181C 44;50;14 49;55;19 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. H221Y is a nonpolymorphic accessory NNRTI-selected mutation that usually occurs in combination with Y181C. 2015 Virology journal Discussion HIV Y181C;H221Y 100;0 105;5 NNRTI 36 41 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. H221Y slightly decreased T215Y/V179E/Y181C resistance to AZT, d4T and 3TC. 2015 Virology journal Discussion HIV T215Y;V179E;Y181C;H221Y 25;31;37;0 30;36;42;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Herein, T215Y and V179D were observed in plasma first compared to PBMC, as with Y181C. 2015 Virology journal Discussion HIV T215Y;V179D;Y181C 8;18;80 13;23;85 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Herein, we did not obtain an effect of Y181C with respect to d4T. 2015 Virology journal Discussion HIV Y181C 39 44 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. However, T215Y/V179E/Y181C/H221Y only resulted in a marked increase in EFV. 2015 Virology journal Discussion HIV H221Y;T215Y;V179E;Y181C 27;9;15;21 32;14;20;26 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. However, these sets of resistance mutations (Y181C/H221Y) conferred cross-resistance to all three NRTIs. 2015 Virology journal Discussion HIV H221Y;Y181C 51;45 56;50 NRTI 98 103 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. However, V179E is associated with low-level resistance to EFV in HIV drug resistance database. 2015 Virology journal Discussion HIV V179E 9 14 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. However, we could not sure if the effect of single V179E is important and further research about role of V179E is needed. 2015 Virology journal Discussion HIV V179E;V179E 51;105 56;110 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In 1994, Larder summarized a series of mutations associated with T215Y and the sequential appearance of these changes. 2015 Virology journal Discussion HIV T215Y 65 70 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In other words, K103N may compensate resistance as a result of T215Y with respect to AZT and d4T. 2015 Virology journal Discussion HIV K103N;T215Y 16;63 21;68 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In plasma, emergence of H221Y followed Y181C for about one half-year, but was combined with Y181C in PBMCs. 2015 Virology journal Discussion HIV H221Y;Y181C;Y181C 24;39;92 29;44;97 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. In the present study, we detected the contribution to AZT, 3TC, d4T and EFV resistance by the double mutation T215Y/V179E. 2015 Virology journal Discussion HIV T215Y;V179E 110;116 115;121 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. It is likely that effect of T215Y predominates as regards the resistance to AZT, 3TC, and d4T. 2015 Virology journal Discussion HIV T215Y 28 33 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. It is not reported that T215Y is associated with resistance of 3TC. 2015 Virology journal Discussion HIV T215Y 24 29 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. It is reported that a differential genetic barrier was found for V106M, V108I, P225H in different HIV-1 subtypes for NNRTI resistance-related substitutions. 2015 Virology journal Discussion HIV P225H;V106M;V108I 79;65;72 84;70;77 NNRTI 117 122 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. It may be the reason for the phenomenon of V179D/E. 2015 Virology journal Discussion HIV V179D;V179E 43;43 50;50 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. One possible explanation for this is that the impact of K103N on EFV resistance may be greater than that of V179E. 2015 Virology journal Discussion HIV K103N;V179E 56;108 61;113 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Our results showed that the co-presence of T215Y/V179E significantly increased AZT and d4T resistance respectively. 2015 Virology journal Discussion HIV T215Y;V179E 43;49 48;54 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Patients should adjust therapy regimen as quickly as possible for better result once T215Y/K103N/Y181C/H221Y emerging. 2015 Virology journal Discussion HIV H221Y;K103N;T215Y;Y181C 103;91;85;97 108;96;90;102 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Results showed that there was no difference in the IC50s of AZT, 3TC, or d4T between T215Y/V179E and T215Y/K103N. 2015 Virology journal Discussion HIV K103N;T215Y;T215Y;V179E 107;85;101;91 112;90;106;96 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. T215Y is interpreted to be resistant to AZT and d4T; and its co-presence with K103N, a mutation to the first-generation NNRTI, did not increase the IC50 with respect to AZT and d4T. 2015 Virology journal Discussion HIV K103N;T215Y 78;0 83;5 NNRTI 120 125 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. T215Y, a classical mutation, is suggested to cause AZT and d4T resistance; and V179D/E is considered to be an NNRTI mutation, by itself reducing NVP and EFV susceptibility approximately 2-fold. 2015 Virology journal Discussion HIV V179D;V179E;T215Y 79;79;0 86;86;5 NNRTI 110 115 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. The IC50 of virus incorporating T215Y/K103N was higher than the virus with T215Y/V179E (P < 0.0001). 2015 Virology journal Discussion HIV K103N;T215Y;T215Y;V179E 38;32;75;81 43;37;80;86 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. The triple-mutation T215Y/V179E/Y181C led to a dramatic increase in resistance in the wild-type virus to all four drugs evaluated. 2015 Virology journal Discussion HIV T215Y;V179E;Y181C 20;26;32 25;31;37 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. This may be affected by T215Y. 2015 Virology journal Discussion HIV T215Y 24 29 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. This may be another reason for more stable of V179E than V179D. 2015 Virology journal Discussion HIV V179D;V179E 57;46 62;51 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. This report indicated that K70R was followed by T215Y and accumulated the cluster mutation M41L/D67N/K70R/T215Y (K219Q), but herein we observed no cluster. 2015 Virology journal Discussion HIV D67N;K70R;M41L;T215Y;K219Q;K70R;T215Y 96;101;91;106;113;27;48 100;105;95;111;118;31;53 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. To confirm the role of Y181C, H221Y and any interaction between them, we analyzed the results of IC50s using appropriate statistical methods. 2015 Virology journal Discussion HIV H221Y;Y181C 30;23 35;28 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. We found resistance of T215Y/V179E to 3TC was significant and this may be affected by V179E. 2015 Virology journal Discussion HIV T215Y;V179E;V179E 23;29;86 28;34;91 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. We found Y181C attenuated resistance of T215Y/V179E to AZT, but it was not significant. 2015 Virology journal Discussion HIV T215Y;V179E;Y181C 40;46;9 45;51;14 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. We rather considered H221Y as a novel mutation along with Y181C. 2015 Virology journal Discussion HIV H221Y;Y181C 21;58 26;63 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. We separately compared the resistance of T215Y/V179E/Y181C and T215Y/V179E/Y181C/H221Y to the wild-type virus. 2015 Virology journal Discussion HIV H221Y;T215Y;T215Y;V179E;V179E;Y181C;Y181C 81;41;63;47;69;53;75 86;46;68;52;74;58;80 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. We therefore analyzed the contribution of the single mutations Y181C and H221Y. 2015 Virology journal Discussion HIV H221Y;Y181C 73;63 78;68 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. With respect to EFV, Y181C, and H221Y both showed increased resistance. 2015 Virology journal Discussion HIV H221Y;Y181C 32;21 37;26 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Y181C and H221Y also decreased the impact of T215Y/K103N on EFV, and their combination with T215Y/K103N augmented the IC50 of EFV. 2015 Virology journal Discussion HIV H221Y;K103N;K103N;T215Y;T215Y;Y181C 10;51;98;45;92;0 15;56;103;50;97;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Y181C is a nonpolymorphic mutation selected in vitro by NNRTIs (NVP, EFV, RPV and ETR) and it is not reported relating to NRTIs. 2015 Virology journal Discussion HIV Y181C 0 5 NNRTI;NRTI 56;122 62;127 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Y181C was demonstrated to decrease the IC50s of AZT and 3TC, and H221Y increased the IC50 of AZT. 2015 Virology journal Discussion HIV H221Y;Y181C 65;0 70;5 26578099 Characterization of two HIV-1 infectors during initial antiretroviral treatment, and the emergence of phenotypic resistance in reverse transcriptase-associated mutation patterns. Y181I/C, which constituted NVP-selected mutations, was reported not only to confer cross-resistance to d4T, but also to improve sensitivity to AZT. 2015 Virology journal Discussion HIV Y181C;Y181I 0;0 7;7 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. In fact, the substitution S375H was suggested to be responsible for the resistance of the CRF01_AE HIV-1 to a potent entry inhibitor, BMS-599793 . 2015 Bioorganic & medicinal chemistry Discussion HIV S375H 26 31 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. In this study we tested 882376 against two mutant pseudoviruses carrying single substitution S375H and S375Y. 2015 Bioorganic & medicinal chemistry Discussion HIV S375H;S375Y 93;103 98;108 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. The S375Y substitution was shown to confer the highest resistance to entry inhibitors NBD-556, NBD-09027 and NBD-11008 as well as BMS-378806 . 2015 Bioorganic & medicinal chemistry Discussion HIV S375Y 4 9 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. The substitutions K432E located near the gp120/CD4 binding region conferred the highest resistance indicated by 6-fold increase in IC50 with respect to the WT (Table 4) suggesting that the gp120/CD4 binding region may be the target of this compound. 2015 Bioorganic & medicinal chemistry Discussion HIV K432E 18 23 gp120;gp120 41;189 46;194 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. This finding was also supported by the poor antiviral activity of 882376 against two mutant pseudoviruses, M475I and M434I carrying amino acid substitutions located at or near the CD4 binding pocket, as shown by the 3-fold increase in IC50 with respect to the WT virus (Table 4). 2015 Bioorganic & medicinal chemistry Discussion HIV M434I;M475I 117;107 122;112 26602829 Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor. This substitution C604Y by abolishing the disulfide loop of gp41 (C598/C604) inhibits the cellular protease furin to recognize its gp160 site and as consequence, induces the production of non-infectious viruses which carry an uncleaved gp160 incapable of binding the CD4 cellular receptor. 2015 Bioorganic & medicinal chemistry Discussion HIV C604Y 18 23 PR;gp160;gp160;gp41 99;131;236;60 107;136;241;64 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. However RTCs with a RT W252A mutant, which can interact with eEF1A but at reduced levels compared to wild type RT (Figs 2 and 3), maintain an RTC complex capable of strong stop DNA synthesis whereas late DNA synthesis occurs at reduced efficiency (Table 4). 2015 PLoS pathogens Discussion HIV W252A 23 28 RT;RT 20;111 22;113 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Interestingly Did B strongly decreased RTC levels and reduced DNA synthesis in cells infected with wild type HIV-1 but not with the RT W252A mutant. 2015 PLoS pathogens Discussion HIV W252A 135 140 RT 132 134 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Our analysis of the W252A RT mutant provides a proof of concept that negatively impacting the RT-eEF1A interaction leads to reduced reverse transcription efficiency and HIV-1 replication. 2015 PLoS pathogens Discussion HIV W252A 20 25 RT;RT;RT 132;26;94 153;28;96 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. Our modeling and MAPPIT experiments testing dimerization of RT subunits support the interpretation that W252A acts by inducing a localized change in RT structure that does not affect RT dimerization. 2015 PLoS pathogens Discussion HIV W252A 104 109 RT;RT;RT 60;149;183 62;151;185 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The contrasting Did B-sensitivity of HIV-1 wild type and W252A mutant RT indicates that Did B affects reverse transcription through the RT-eEF1A interaction and not by off-target effects. 2015 PLoS pathogens Discussion HIV W252A 57 62 RT;RT;RT 102;70;136 123;72;138 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The modeling also predicts that a T253A mutation will not affect RT structure and RT protein containing this mutation efficiently binds to eEF1A in co-IP assays indicating specificity for the W252 region. 2015 PLoS pathogens Discussion HIV T253A 34 39 RT;RT 65;82 67;84 26624286 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. The W252A and L303A mutants, in particular, are interesting because their side-chains are buried in the RT core and unlikely contact points between RT and eEF1A, and their individual mutation to alanine imparts a localized structural change that is sufficient to disrupt RT interaction with eEF1A. 2015 PLoS pathogens Discussion HIV L303A;W252A 14;4 19;9 RT;RT;RT 104;148;271 106;150;273 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. On the other hand, a highly polymorphic minor INI accessory mutation (V201I) was detected in 82 % of the isolates which is significantly higher compared with the report from Cameron and Quebec subtype C isolates and consistent with South African isolates. 2015 Journal of translational medicine Discussion HIV V201I 70 75 IN 46 49 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. The absence of the non-polymorphic minor INI-resistance mutations (E157Q which could be selected by raltegravir reducing elvitegravir susceptibility) in the current study is similar with a recent report from Brazilian subtype C isolates and several other studies. 2015 Journal of translational medicine Discussion HIV E157Q 67 73 IN 41 44 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. The occurrences of polymorphic minor INI-accessory mutations (L74I, T125A, V165I, T206S, L234I and V201I) are similar to previous HIV-1C isolates from South Africa. 2015 Journal of translational medicine Discussion HIV L234I;L74I;T125A;T206S;V165I;V201I 89;62;68;82;75;99 94;66;73;87;80;104 IN 37 40 26626277 Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates. This includes T66IAK, E92Q, F121Y, G140SA, Y143HCR, Q146P, S147G, Q148KHR, and N155HS; (2) minor INI-resistance mutations were defined as non-polymorphic or minimally polymorphic mutations that reduce INI susceptibility 50% of cases). 2016 PloS one Discussion HIV Y135F;Y135F 57;213 62;218 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. 4 A14C/E45C to E45A and E45A/R132T). 2016 Retrovirology Discussion HIV E45A;E45A;E45C;R132T;A14C 15;24;7;29;2 19;28;11;34;6 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. According to those analyses, the capsid disulfide crosslinking mutants, A204C and A14C/E45C, are the most stable of the four mutants analyzed in our study. 2016 Retrovirology Discussion HIV A14C;A204C;E45C 82;72;87 86;77;91 Capsid 33 39 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Finally, the E45A/R132T double mutant has previously been shown to partially restore viral infectivity lost following the original E45A mutation while maintaining the latter's stability in vitro. 2016 Retrovirology Discussion HIV E45A;E45A;R132T 13;131;18 17;135;23 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. In contrast, this reinforcement was not observed in the case of the E45A mutant: the stiffness value for E45A CA assemblies was nearly identical to that of its isolated native core. 2016 Retrovirology Discussion HIV E45A;E45A 68;105 72;109 Capsid 110 112 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. In support of their hypothesis, we find that the stiffness of E45A/R132T mutant CA assemblies is similar to that of the E45A mutant. 2016 Retrovirology Discussion HIV E45A;E45A;R132T 62;120;67 66;124;72 Capsid 80 82 26979152 Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid. Mutations E45A and E45A/R132T increase hydrophobic intra-hexamer interactions, the double A14C/E45C mutation introduces covalent intra-hexamer crosslinking via a disulfide bond, while A204C introduces inter-hexamer disulfide crosslinking. 2016 Retrovirology Discussion HIV A14C;A204C;E45A;E45A;E45C;R132T 90;184;10;19;95;24 94;189;14;23;99;29 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. Alternatively, the person who transmitted the virus may have interrupted treatment before the transmission event, thus reducing the likelihood of transmitting the M184V virus. 2016 AIDS research and human retroviruses Discussion HIV M184V 163 168 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. Although recently infected patients not on ART are expected to have viral loads >10,000 RNA copies/ml, the use of genotyping methods with higher sensitivity below 10,000 RNA copies/ml will enhance the detection of cases of transmitted M184V mutation, which has been shown to be associated with lower viral loads. 2016 AIDS research and human retroviruses Discussion HIV M184V 235 240 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. From the 2012 samples, there were two cases of transmission of the K65R mutation, which is selected for by tenofovir (TDF) and which had been introduced into first-line regimens in South Africa 2 years earlier in 2010. 2016 AIDS research and human retroviruses Discussion HIV K65R 67 71 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. Generally, the prevalence of transmitted K65R mutants has been low in settings with widespread exposure to tenofovir-containing ART regimens. 2016 AIDS research and human retroviruses Discussion HIV K65R 41 45 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. However, the reduced fitness associated with the M184V mutation might have resulted in the fast reversion to wild type at this codon, if the transmitted virus had the mutation. 2016 AIDS research and human retroviruses Discussion HIV M184V 49 54 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. It had been previously shown that K65R emerges more frequently in subtype C viruses due to a difference in the template nucleotide sequence. 2016 AIDS research and human retroviruses Discussion HIV K65R 34 38 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. The first was a male individual infected with a virus with multiclass resistance (NNRTI+NRTI), including two TAMs (D67N and K219Q) and the T215 revertant (T215A). 2016 AIDS research and human retroviruses Discussion HIV D67N;K219Q;T215A 115;124;155 120;129;160 NNRTI;NRTI 82;88 87;92 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. The mutations contributing to most of the resistance in 2011 and 2012 were the NNRTI mutations, specifically K103N has been shown to persist in plasma for as long as 3 years in primary infection. 2016 AIDS research and human retroviruses Discussion HIV K103N 109 114 NNRTI 79 84 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. The second was a case of transmission of a virus with M184V mutation plus five TAMs but with no NNRTI mutations. 2016 AIDS research and human retroviruses Discussion HIV M184V 54 59 NNRTI 96 101 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. There have been reports of rapid emergence of the K65R mutation in patients failing TDF-based regimens infected with subtype C viruses. 2016 AIDS research and human retroviruses Discussion HIV K65R 50 54 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. This could better shed more light on M184V TDR as well as the TAM revertants. 2016 AIDS research and human retroviruses Discussion HIV M184V 37 42 27002368 Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. With that time frame, the patient would also have been expected to have the M184V mutation in addition to the three NRTI mutations. 2016 AIDS research and human retroviruses Discussion HIV M184V 76 81 NRTI 116 120 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. However, had a baseline INSTI genotypic resistance test been available and had the effect of Q148N been known, a different regimen would likely have been chosen. 2016 AIDS research and human retroviruses Discussion HIV Q148N 93 98 INSTI 24 29 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Of 1,120 integrase sequences from patients receiving raltegravir in GenBank as of June 2015, 23%, 8%, and 1% had the previously characterized INSTI-resistance mutations Q148H, Q148R, and Q148K, respectively. 2016 AIDS research and human retroviruses Discussion HIV Q148H;Q148K;Q148R 169;187;176 174;192;181 IN;INSTI 9;142 18;147 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Q148N is also the only mutation other than Q148H/R/K that has been shown to have strand transfer activity in biochemical assays. 2016 AIDS research and human retroviruses Discussion HIV Q148H;Q148K;Q148R;Q148N 43;43;43;0 52;52;52;5 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. Q148N was present in viruses from three raltegravir-experienced individuals and is the only other mutation at this position detected in GenBank sequences. 2016 AIDS research and human retroviruses Discussion HIV Q148N 0 5 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. The patient's response to therapy may reflect the relatively low-level reduction in elvitegravir susceptibility associated with Q148N and the relatively low plasma HIV-1 RNA level at the time of diagnosis. 2016 AIDS research and human retroviruses Discussion HIV Q148N 128 133 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. The rarity of Q148N and its weaker association with INSTI resistance suggest that it may be a revertant mutation arising from single nucleotide substitutions in viruses that once harbored Q148H (CAC or CAT) or Q148K (AAA or AAG) = >Q148N (AAC or AAT). 2016 AIDS research and human retroviruses Discussion HIV Q148H;Q148K;Q148N;Q148N 188;210;14;232 193;215;19;237 INSTI 52 57 27009474 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. There have been too few published sequences obtained from elvitegravir-experienced individuals to determine whether Q148N occurs at a higher frequency after elvitegravir treatment than after raltegravir treatment. 2016 AIDS research and human retroviruses Discussion HIV Q148N 116 121 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. However, our data shown in Table 2 illustrated L210W, unlike other alleles, had only a call rate per allele equal to 80.5%. 2016 PloS one Discussion HIV L210W 47 52 27092551 Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY(R) System. Strictly, we will not accept the detection for this allele as completely successful and thus a redesign of the extension primers for detecting L210W will be required in future. 2016 PloS one Discussion HIV L210W 143 148 27107820 HIV-1 capsid is involved in post-nuclear entry steps. However this hypothesis is not fully convincing because viruses harboring the A105S and N74D mutations are insensitive to C-A1, they do not show accumulation of capsid in the nucleus yet they are capable of integrating. 2016 Retrovirology Discussion HIV A105S;N74D 78;88 83;92 Capsid 161 167 27107820 HIV-1 capsid is involved in post-nuclear entry steps. Mutant viruses N74D and A105S proceed through a capsid-independent pathway, which makes them insensitive to C-A1. 2016 Retrovirology Discussion HIV A105S;N74D 24;15 29;19 Capsid 48 54 27107820 HIV-1 capsid is involved in post-nuclear entry steps. The N74D mutant virus remained insensitive to Nup153 depletion, presumably because it had already lost almost all capsid by the time it entered the nucleus. 2016 Retrovirology Discussion HIV N74D 4 8 Capsid 114 120 27107820 HIV-1 capsid is involved in post-nuclear entry steps. We identified another capsid point mutation, N74D, conferring resistance to C-A1. 2016 Retrovirology Discussion HIV N74D 45 49 Capsid 22 28 27107820 HIV-1 capsid is involved in post-nuclear entry steps. We previously suggested that C-A1 targeted capsid because serial passaging of HIV-1 in the presence of the drug resulted in the emergence of a drug-resistant virus with the A105S capsid mutation. 2016 Retrovirology Discussion HIV A105S 173 178 Capsid;Capsid 43;179 49;185 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. In addition, T215F/Y confers high-level resistance to AZT and d4T and varying degrees of resistance to most NRTIs. 2016 PloS one Discussion HIV T215F;T215Y 13;13 20;20 NRTI 108 113 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. In our study, the most frequent NRTIs associated mutation was M184V (76%), followed by T215F/Y (26.8%). 2016 PloS one Discussion HIV M184V;T215F;T215Y 62;87;87 67;94;94 NRTI 32 37 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Intermediate to high resistance levels to NRTIs in the ARV drug-experienced subjects were reported in Panama in previous years (2004-2005) and were associated to mutations L74V (2.4%), T215F/Y (3.6%) and M184V (1.2%). 2016 PloS one Discussion HIV L74V;M184V;T215F;T215Y 172;204;185;185 176;209;192;192 NRTI 42 47 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. L74V was the second most frequent mutation in subjects using the alternative first line-scheme consisting of EFV + 2 NRTIs, mainly ABC (37.3%) or ddI (23.5%) or AZT (19.6%). 2016 PloS one Discussion HIV L74V 0 4 NRTI 117 122 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. M184V is selected during 3TC and FTC treatment and has been shown to confer high-level resistance to these drugs. 2016 PloS one Discussion HIV M184V 0 5 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Mutations K103N and P225H are preferentially selected by EFV, which is a second generation NNRTI. 2016 PloS one Discussion HIV K103N;P225H 10;20 15;25 NNRTI 91 96 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Our mutation pattern analyses showed that the most frequent SDRM were: K103N (4.0%) and P225H (2.0%) for NNRTIs, T215 revertants (2.4%) and M41L (2.0%) for NRTIs, and M46L/I (1.2%) for PIs. 2016 PloS one Discussion HIV K103N;M41L;M46I;M46L;P225H 71;140;167;167;88 76;144;173;173;93 NNRTI;NRTI;PI 105;156;185 111;161;188 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Previously reported NNRTIs mutations for the 2004 to 2005 period in ARV drug-experienced subjects exposed to AZT or d4T + 3TC or ddI + EFV or NFV or IDV reported K103N at a lower frequency (4.9%), together with mutations L100I (1.2%) and Y318F (1.2%). 2016 PloS one Discussion HIV K103N;L100I;Y318F 162;221;238 167;226;243 NNRTI 20 26 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. The pattern of mutations associated with NNRTIs in ARV drug-experienced subjects on first line-schemes reveals a high prevalence of mutations K103N (69.0%) and P225H (27.2%). 2016 PloS one Discussion HIV K103N;P225H 142;160 147;165 NNRTI 41 47 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Therefore, the observed high level of resistance to 3TC and FTC in 75.6% of ARV drug-experienced subjects may be explained by the high frequency of M184V, irrespective of ART scheme in use. 2016 PloS one Discussion HIV M184V 148 153 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. These two ARV drugs are administered alternatively when K103N, V106A/M and P225H are already expressed, as these mutations are not selected by these drugs. 2016 PloS one Discussion HIV K103N;P225H;V106A;V106M 56;75;63;63 61;80;70;70 27119150 HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes. Thus, the impact of TAMs need to be better evaluated in coming years since HIV-infected subjects with mutations M184V alone, P119S/T165A/M184V combined or T69 insertion complex, including T210W and T215Y, may have significantly decreased susceptibility to the novel drug Ed4T. 2016 PloS one Discussion HIV M184V;P119S;T165A;M184V;T210W;T215Y 137;125;131;112;188;198 142;130;136;117;193;203 HIV infections 75 87 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Another mutation that was investigated was the E138K because it was reported to be 77% prevalent in RPV-failed patients from the ECHO and THRIVE studies. 2016 PloS one Discussion HIV E138K 47 52 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. In our study, 60.8% and 79.2% were TAM and M184V, respectively. 2016 PloS one Discussion HIV M184V 43 48 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Likewise, our study detected only 0.4% of patients that have failed the first-line NNRTI regimen with E138K. 2016 PloS one Discussion HIV E138K 102 107 NNRTI 83 88 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Moreover, in combination with other mutations such as V90I, V106I, V179F, G190ASCVT and H221Y, it can synergistically exacerbate the resistance of ETR and RPV. 2016 PloS one Discussion HIV G190A;G190C;G190S;G190T;G190V;H221Y;V106I;V179F;V90I 74;74;74;74;74;88;60;67;54 83;83;83;83;83;93;65;72;58 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. On the other hand, K103N or K103S, a potential mutation induced by EFV, has no effect on the susceptibility of ETR and RPV. 2016 PloS one Discussion HIV K103N;K103S 19;28 24;33 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. The most common mutation for RPV in patients who failed NVP-based regimen, compared to the EFV-based regimen, was Y181C (52.7% vs. 2016 PloS one Discussion HIV Y181C 114 119 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. This particular nonpolymorphic mutation, Y181C, is one of the worst NNRTI-RAM and it has an intermediate-level resistance to both ETR and RPV. 2016 PloS one Discussion HIV Y181C 41 46 NNRTI 68 73 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. We next examined the mutation profile among patients with first-line regimen failure and observed that most of the patients had thymidine analogue mutations (TAMs) with or without M184V and NNRTI RAMs. 2016 PloS one Discussion HIV M184V 180 185 NNRTI 190 195 27120449 Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study. Y181C is notoriously well-known for conferring a 5-fold reduction in susceptibility to ETR and a 3-fold reduction in susceptibility to RPV. 2016 PloS one Discussion HIV Y181C 0 5 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Although DOR apparently did not select for the E138K mutation in cell culture, we found that this mutation did reduce the susceptibility of HIV-1 to DOR by about 20-fold. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K 47 52 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Although the E138 residue does not make any direct contacts with DOR, the binding of DOR within the pocket caused the position of this residue to shift substantially, which could prevent the interaction between E138K of the p51 subunit and K101 of the p66 subunit. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K 211 216 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. As has already been reported, the E138K mutation does not cause a significant reduction in susceptibility to RPV in cell culture assays (including ours). 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K 34 39 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Based on the structure of RPV bound to RT, it is not surprising that the K101P caused a substantial decrease in susceptibility to RPV. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K101P 73 78 RT 39 41 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. However, it is possible that DOR would not be effective in suppressing the selection and replication of E138K mutants that arise during RPV-containing cART. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K 104 109 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. However, it might be possible to develop cART regimens in which DOR was combined with RPV; however, as previously mentioned, E138K mutation could pose a problem for this combined strategy. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K 125 130 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Importantly, classical NNRTI mutants, for example Y188L, caused a substantial drop in DOR susceptibility and other classical NNRTI mutants including K103N and K103N/Y181C caused more modest drops in susceptibility to DOR. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;K103N;Y181C;Y188L 149;159;165;50 154;164;170;55 NNRTI;NNRTI 23;125 28;130 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Interestingly, the E138K mutant caused a 20-fold drop in susceptibility to DOR. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K 19 24 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. K101P would appear to cause a steric clash with RPV in the binding pocket and the interaction of E138 with K101 would be lost. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K101P 0 5 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. Mutations at V106, with or without additional secondary mutations (F227L, L234I, and F227L/L234I), caused substantial decreases in susceptibility to DOR. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227L;F227L;L234I;L234I 67;85;74;91 72;90;79;96 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The branched, hydrophobic side chain of V106 interacts with the pyridone core of DOR; in the presence of the V106A mutation, this important contact is lost. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106A 109 114 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The complication is that, in HIV-infected individuals, RPV selects for the E138K mutation. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K 75 80 HIV infections 29 41 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The K101P/V179I mutant caused a large decrease in RPV susceptibility because it affects both the contacts between the amine linkers and pyrimidine core with the residues of the binding pocket by introducing steric clash through the branched isoleucine and the cyclic proline. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K101P;V179I 4;10 9;15 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The P236L mutation causes a modest decrease in DOR susceptibility by introducing clash and preventing the CH-pi interaction between the triazolone of DOR and P236. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV P236L 4 9 PI 109 111 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The Y181I mutant also displayed a decrease in susceptibility to RPV, unlike the other mutant at this position, Y181C, likely because of the unavoidable steric clash from beta-branched isoleucine that prevents RPV from recruiting Y183 toward the NNRTI binding pocket to compensate for the loss of interaction between Y181 and its phenyl moiety. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Y181C;Y181I 111;4 116;9 NNRTI 245 250 27124362 Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. The Y188L mutation causes the loss of the pi-pi stacking interaction, which in turn reduces the potency of DOR inhibition, while the lack of interaction with Y181 explains the fact that the Y181C and Y181I mutants are susceptible to DOR. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Y181C;Y181I;Y188L 190;200;4 195;205;9 PI;PI 42;45 44;47 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. A related question is why the R263K substitution that confers low-level resistance to DTG is selected at all. 2016 Retrovirology Discussion HIV R263K 30 35 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Although small differences in integration levels were observed for single RT mutants and double R263K-RT mutants, these were not significant (Student's t test, P values >0.05), whereas statistical significance was achieved for L74V versus R263K-L74V (Student's t test, P = 0.03) and M184I versus R263K-M184I (Student's t test, P = 0.05). 2016 Retrovirology Discussion HIV L74V;L74V;M184I;M184I;R263K;R263K;R263K 227;245;283;302;96;239;296 231;249;288;307;101;244;301 RT;RT 74;102 76;104 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Although this mutation alone confers up to 100-fold-1000-fold less susceptibility to 3TC, regimens containing this drug have been shown to maintain efficacy in the treatment of HIV-1, perhaps because the M184V mutation is associated with a loss of replicative fitness and increased fidelity of RT activity. 2016 Retrovirology Discussion HIV M184V 204 209 RT 294 296 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. And these differences were further magnified in the presence of H51Y. 2016 Retrovirology Discussion HIV H51Y 64 68 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Another possibility is that DTG may reach anatomical compartments that are not susceptible to other inhibitors, effectively preventing the emergence of R263K and other substitutions; this possibility is supported by recent reports of persistent HIV replication under suppressive ARV therapy. 2016 Retrovirology Discussion HIV R263K 152 157 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Compared to WT virus, the R263K substitution as well as some other major mutations E92Q, Q148R and N155H, reported in the RAL- and/or EVG-resistance pathways, can emerge from a single nucleotide change in most HIV-1 strains. 2016 Retrovirology Discussion HIV E92Q;N155H;Q148R;R263K 83;99;89;26 87;104;94;31 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Double mutant viruses with RT and R263K integrated less efficiently than either viruses with single RT mutations or WT whereas DNA integration levels in almost all triple mutant viruses were very low or undetectable. 2016 Retrovirology Discussion HIV R263K 34 39 RT;RT 27;100 29;102 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. First, our study confirmed previous observations on the decrease of viral replication in viruses containing both M184I/V plus R263K. 2016 Retrovirology Discussion HIV M184I;M184V;R263K 113;113;126 120;120;131 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. For example, H51Y/R263K-K65R triple mutants resulted in appreciable levels of integration that were comparable with those observed with the double mutant R263K-K65R virus (Student's t test, P = 0.2), whereas the same H51Y/R263K-K65R combination of substitutions attenuated infectivity by 7.8-fold compared to the R263K-K65R combination that only caused a 1.7-fold decrease. 2016 Retrovirology Discussion HIV H51Y;H51Y;K65R;K65R;K65R;K65R;R263K;R263K;R263K;R263K 13;217;24;160;228;319;18;154;222;313 17;221;28;164;232;323;23;159;227;318 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. For example, N155H virus caused sixfold and fivefold decreases in susceptibility to RAL and EVG and E92Q conferred more than a 50-fold decrease in EVG susceptibility. 2016 Retrovirology Discussion HIV E92Q;N155H 100;13 104;18 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Given that the R263K substitution has been reported in some INSTI-naive patients in the SAILING study and in tissue culture selections, we aimed to investigate the effects of R263K and its secondary mutation H51Y together with major RTI-resistance substitutions at positions K65R, L74V, K103N, E138K, and M184I/V, in terms of viral replication and integration capacity in the absence of drugs. 2016 Retrovirology Discussion HIV E138K;H51Y;K103N;K65R;L74V;M184I;M184V;R263K;R263K 294;208;287;275;281;305;305;15;175 299;212;292;279;285;312;312;20;180 INSTI;RT 60;233 65;236 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. H51Y also has a further detrimental effect on viral replication capacity. 2016 Retrovirology Discussion HIV H51Y 0 4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. H51Y, are so impaired in replication capacity that they cannot be detected by ordinary Sanger sequencing. 2016 Retrovirology Discussion HIV H51Y 0 4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In addition, triple mutants bearing the H51Y/R263K-RT mutations resulted in either undetectable integration levels (in cases of H51Y/R263K plus single substitutions K103N, E138K or M184I. 2016 Retrovirology Discussion HIV E138K;H51Y;H51Y;K103N;M184I;R263K;R263K 172;40;128;165;181;45;133 177;44;132;170;186;50;138 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In contrast, the common M184V mutation develops rapidly in patients failing lamivudine (3TC) therapy. 2016 Retrovirology Discussion HIV M184V 24 29 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In our study, decreased replication was also observed with the R263K-L74V virus and this was greatly exacerbated by the additional presence of H51Y. 2016 Retrovirology Discussion HIV H51Y;L74V;R263K 143;69;63 147;73;68 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. In some of these cases, both K65R and M184V/I have co-emerged with integrase mutations. 2016 Retrovirology Discussion HIV K65R;M184I;M184V 29;38;38 33;45;45 IN 67 76 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. K103N is a very common NNRTI mutation that only minimally affects viral replication in the absence of drug pressure. 2016 Retrovirology Discussion HIV K103N 0 5 NNRTI 23 28 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. L74V and M184I are associated with resistance against ABC, which is co-formulated with DTG and lamivudine in a single daily pill; these results suggest that this combination may provide an advantage in regard to pathways leading to drug resistance. 2016 Retrovirology Discussion HIV M184I;L74V 9;0 14;4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. L74V is associated with a reduced replicative capacity of HIV-1 of about 11 % compared to WT. 2016 Retrovirology Discussion HIV L74V 0 4 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Most commonly, mutations at N155H and Q148H/R have been observed in combination with M184I/V or less often with K65R. 2016 Retrovirology Discussion HIV K65R;M184I;M184V;N155H;Q148H;Q148R 112;85;85;28;38;38 116;92;92;33;45;45 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Nevertheless, the combination of M184V with K65R has caused virological failures in patients receiving regimens containing two N(t)RTIs, 3TC and tenofovir. 2016 Retrovirology Discussion HIV K65R;M184V 44;33 48;38 NRTI 127 135 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. On the other hand, R263K is more commonly detected in HIV-positive individuals who experience treatment failure with DTG even though this substitution only modestly decreases DTG susceptibility (about twofold) as well as HIV-1 replication capacity. 2016 Retrovirology Discussion HIV R263K 19 24 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. One possibility is that viruses that contain R263K and other resistance mutations. 2016 Retrovirology Discussion HIV R263K 45 50 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Similar results were obtained with K103N together with R263K/H51Y, with no detection of p24 at days 3 and 7 p.i. 2016 Retrovirology Discussion HIV H51Y;K103N;R263K 61;35;55 65;40;60 p24 88 91 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. Similar sixfold-sevenfold levels of resistance to RAL and EVG have been reported for Q148R virus. 2016 Retrovirology Discussion HIV Q148R 85 90 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The addition of R263K to K103N caused only a small loss in viral replication capacity compared to K103N alone. 2016 Retrovirology Discussion HIV K103N;K103N;R263K 25;98;16 30;103;21 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The addition of R263K to viruses containing M184I or M184V, K65R, and E138K yielded fewer viruses that were replication competent than when only single RT mutations were studied. 2016 Retrovirology Discussion HIV E138K;K65R;M184I;M184V;R263K 70;60;44;53;16 75;64;49;58;21 RT 152 154 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. The answer is probably that R263K does confer a higher level of resistance against DTG as a single substitution than does any of the resistance mutations associated with RAL or EVG (1). 2016 Retrovirology Discussion HIV R263K 28 33 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. These findings are consistent with earlier results that the emergence of M184I was delayed in the presence of R263K under lamivudine drug pressure and that the M184I substitution was detected in the case of the H51Y/R263K virus. 2016 Retrovirology Discussion HIV H51Y;M184I;M184I;R263K;R263K 211;73;160;110;216 215;78;165;115;221 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. This is fortuitous for the use of DTG even in patients who are not adherent to therapy, especially because the R263K substitution does not seem to be able to co-exist together with mutations at positions 143 and 148 that are frequently observed in patients who have failed therapy with RAL or EVG (14). 2016 Retrovirology Discussion HIV R263K 111 116 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. We also confirmed the deficits caused by R263K together with other RTI mutations. 2016 Retrovirology Discussion HIV R263K 41 46 RT 67 70 27130466 Effect on HIV-1 viral replication capacity of DTG-resistance mutations in NRTI/NNRTI resistant viruses. We previously demonstrated that the secondary mutation H51Y developed after the emergence of R263K in vitro and caused a higher level of resistance against DTG, about 16-fold in TZM-bl cells and sevenfold in the PhenoSense Integrase Replication assay. 2016 Retrovirology Discussion HIV H51Y;R263K 55;93 59;98 IN 224 233 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. Although for the remaining patient we could not demonstrate the failing mutation with Sanger sequencing, using a more sensitive test, resulted in the correct identification of the failing mutations [N155H (9.7 %) and T97A (12.42 %)] suggesting that, given the superiority of massive parallel sequencing, this should be the tool recommended for testing proviral DNA in virologically suppressed patients, although at present it is an expensive tool that may not be feasible in some laboratories. 2016 BMC infectious diseases Discussion HIV N155H;T97A 199;217 204;221 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. Only the accumulation of Q148H/R/K, together with other secondary mutations broadens DTG activity. 2016 BMC infectious diseases Discussion HIV Q148H;Q148K;Q148R 25;25;25 34;34;34 27177767 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. Secondly, only the N155H pathway was confirmed in some patients and it is possible that resistance pathways other than N155H, that could have emerged before N155H was established, may have been archived in the proviral DNA of the patients compromising DTG activity. 2016 BMC infectious diseases Discussion HIV N155H;N155H;N155H 19;119;157 24;124;162 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. According to our analysis of subtypes A and D from Stanford and AMPATH, these high K65R rates are not explained by the adjacent poly-A template, as proposed for subtype C. 2016 Journal of the International AIDS Society Discussion HIV K65R 83 87 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Although very small in numbers, these data also support high K65R occurrence in subtype C (100%, 4/4) and introduce its high occurrence in subtype D (50%, 2/4). 2016 Journal of the International AIDS Society Discussion HIV K65R 61 65 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. First, our data support the reported association between K65R, Y181C and G190A, suggesting synergistic fitness effects, and extend it to NVP (not only EFV) treatment. 2016 Journal of the International AIDS Society Discussion HIV G190A;K65R;Y181C 73;57;63 78;61;68 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. In addition, traditional Sanger sequencing may have underestimated K65R and other minority resistant variants; we were unable to follow the prior ART group from ART start or switch to TDF; VL failure was not confirmed; adherence was self-reported; time of failure was not quantified; and lastly, enrolled participants were on TDF for various time periods and those lost to follow-up were not included, potentially underestimating actual failure rates. 2016 Journal of the International AIDS Society Discussion HIV K65R 67 71 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. In fact, in this study, 31% of the patients had no K65R, some after as many as 33 months of TDF-based first-line ART. 2016 Journal of the International AIDS Society Discussion HIV K65R 51 55 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. In fact, reports in subtype C from settings in which virologic monitoring is routine, including South Africa, demonstrate lower K65R rates. 2016 Journal of the International AIDS Society Discussion HIV K65R 128 132 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. K65R is a TDF signature mutation conferring resistance to all NRTIs but AZT, is rarely transmitted, is less common in subtype B-infected patients failing therapy, and is variable in RLS. 2016 Journal of the International AIDS Society Discussion HIV K65R 0 4 NRTI 62 67 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Our data offer new information on the interplay between subtype and K65R. 2016 Journal of the International AIDS Society Discussion HIV K65R 68 72 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Second, lack of TAMs and no prior TAM-associated medication exposure may facilitate K65R development. 2016 Journal of the International AIDS Society Discussion HIV K65R 84 88 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Several considerations are relevant to the demonstrated increased K65R levels. 2016 Journal of the International AIDS Society Discussion HIV K65R 66 70 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. The high barrier to K65R development as reported in resource-rich settings may reflect high potency of K65R-selecting drugs, significant viral fitness constraints and unique RNA structural considerations. 2016 Journal of the International AIDS Society Discussion HIV K65R;K65R 20;103 24;107 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. The lack of routine virologic monitoring at AMPATH at the time of this study likely played a role in K65R development, as evidenced by indicators of advanced disease like low CD4, high WHO stages, more RT mutations and potentially failing therapy for longer. 2016 Journal of the International AIDS Society Discussion HIV K65R 101 105 RT 202 204 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. The latter may be particularly true for K65R detection because its presence would indicate the need to switch to AZT and its absence would indicate the possibility to recycle TDF in a subsequent first- or second-line regimen. 2016 Journal of the International AIDS Society Discussion HIV K65R 40 44 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. These data augment prior contradicting reports from Europe, one reporting low K65R rates in subtype A compared to other subtypes and another reporting no inter-subtype difference. 2016 Journal of the International AIDS Society Discussion HIV K65R 78 82 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. These results should reassure clinicians in RLS to switch to TDF-based first-line ART, despite prior concerns of K65R development in patients with prior d4T exposure. 2016 Journal of the International AIDS Society Discussion HIV K65R 113 117 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Third, among failing patients, high levels of resistance were observed across subtypes, with high K65R rates posing particular concern. 2016 Journal of the International AIDS Society Discussion HIV K65R 98 102 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Though failure and K65R development were not associated with NNRTI backbone as previously suggested, such associations should continue to be investigated given our small sample-size. 2016 Journal of the International AIDS Society Discussion HIV K65R 19 23 NNRTI 61 66 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. Though mutation frequencies in this study, other than K65R, were similar to prior reports, unique mutation patterns in 58% of the patients and specific mutation co-occurrence support the need for continued research on subtype-specific resistance, particularly with changing treatment guidelines. 2016 Journal of the International AIDS Society Discussion HIV K65R 54 58 27231099 Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. We, for the first time, report high K65R occurrence (71%) upon TDF-based first-line failure in subtype A, a globally prevalent subtype and the most common in Kenya. 2016 Journal of the International AIDS Society Discussion HIV K65R 36 40 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Fifth, the A105T mutation, though outside the cyclophilin-binding loop, can affect viral sensitivity to Cs. 2016 Journal of virology Discussion HIV A105T 11 16 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. First, cDNA reverse transcription intermediates of both N74D and P90A mutant viruses are sensed and trigger type I IFN production after infection of MDMs. 2016 Journal of virology Discussion HIV N74D;P90A 56;65 60;69 RT 12 33 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Fourth, HIV-1 CA P90A binds CypA with reduced affinity, such that the stabilizing effects of CypA binding to CA are lost. 2016 Journal of virology Discussion HIV P90A 17 21 Capsid;Capsid 14;109 16;111 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Here, we analyzed the sensitivity of HIV-1 CA mutants N74D, A105T, as well as P90A, to IFN-alpha-induced blocks and found that their infectivities were reduced further after IFN-alpha treatment of THP-1 cells, MDMs, or CD4+ T cells than that of wild-type virus. 2016 Journal of virology Discussion HIV A105T;N74D;P90A 60;54;78 65;58;82 Capsid 43 45 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. However, the replication defects of N74D and P90A viruses in MDMs may be explained by a combination of increased cGAS sensing, IFN-alpha induction, and increased sensitivity to the IFN-alpha-induced effectors themselves. 2016 Journal of virology Discussion HIV N74D;P90A 36;45 40;49 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Multiple lines of evidence suggest that CA mutants N74D, A105T or P90A have defects in capsid stability and uncoating, possibly due to altered interactions with host factors. 2016 Journal of virology Discussion HIV A105T;N74D;P90A 57;51;66 62;55;70 Capsid;Capsid 87;40 93;42 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Second, N74D shows delayed uncoating kinetics in TRIMCyp-expressing cells and a Cs washout assay, suggesting that this mutation perturbs uncoating. 2016 Journal of virology Discussion HIV N74D 8 12 27279606 Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Third, N74D is more susceptible to the NNRTI nevirapine compared to wild-type virus, suggesting that wild-type capsid integrity may help protect the virus from antiviral drugs. 2016 Journal of virology Discussion HIV N74D 7 11 Capsid;NNRTI 111;39 117;44 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. In addition, preexisting minority Y181C variants were associated with a risk of virological failure in patients initiated on first-line efavirenz (EFV)-containing ART and in EFV exposed treatment experienced patients. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Y181C 34 39 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. In our study, Y188C and Y181C were detected in 23% and 11%, respectively, of patients as minority variants. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Y181C;Y188C 24;14 29;19 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. It is therefore important to interpret low abundance K65R mutations in subtype C with caution. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 53 57 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. K65R was detected in 11% of patients at low frequencies (1%-2.6%). 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 0 4 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Most of the K103N mutations were detected between frequencies of 17% and 59%, making it the predominant variant in the quasispecies for those specimens (Table 2). 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N 12 17 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. The mechanism for higher levels of K65R in subtype C seems to be template specific, where a preferential pause in subtype C reverse transcription at position 65 AAG-AGG is seen. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 35 39 RT 124 145 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. The most common mutations (30%) detected were K103N and V106M, which are associated with high-level NNRTI resistance. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;V106M 46;56 51;61 NNRTI 100 105 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. The prevalence of transmitted NNRTI resistance in KwaZulu-Natal has increased from below 5% in 2007 to 5%-15% in 2010 with the most commonly detected mutation being the K103NS. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;K103S 169;169 175;175 NNRTI 30 35 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. There are reports of higher levels of K65R detection in HIV-1 subtype C among patients failing first-line TDF-based ART and in ART-naive patients. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 38 42 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Third, the number of patients with NNRTI mutations among those failing NNRTI-based ART is high in rural South Africa, ie, 82% in both adults and children, with K103NS again being the most commonly detected NNRTI mutation. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;K103S 160;160 166;166 NNRTI;NNRTI;NNRTI 35;71;206 40;76;211 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Two (7%) patients harbored the K70R mutation while no other TAMs were found. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K70R 31 35 27327263 HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission. Varghese et al showed that using UDS which is PCR dependent for the sequencing of subtype C, RT KKK template may result in spurious detection of K65R. 2016 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 145 149 RT 93 95 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. CPSF6 is known to bind to the hydrophobic pocket, formed between adjacent CA monomers, and this pocket is known to be disrupted by the N74D mutation. 2016 PLoS pathogens Discussion HIV N74D 135 139 Capsid 74 76 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Critically, however, we also observe here that the N74D and P90A mutants are not similarly affected by KIF5B depletion (Fig 3). 2016 PLoS pathogens Discussion HIV N74D;P90A 51;60 55;64 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Despite these methodological differences, both methods demonstrated that the N74D mutation prevented the association of Nup358 with viral cores. 2016 PLoS pathogens Discussion HIV N74D 77 81 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Differences in the colocalization analysis and PLA analysis suggest that the P90A mutation reduces, but does not eliminate, the binding of Nup358 to CA. 2016 PLoS pathogens Discussion HIV P90A 77 81 Capsid 149 151 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. However, when the interaction between CA and Nup358 was measured by PLA, we observed a significant degree of interaction between P90A CA and Nup358, while the N74D mutant did not induce significantly more puncta than was observed following WT/DeltaEnv or mock infection (Fig 6). 2016 PLoS pathogens Discussion HIV N74D;P90A 159;129 163;133 Capsid;Capsid 38;134 40;136 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. In support of this possibility, Rasaiyaah and coworkers have observed that the same N74D and P90A mutants which we observe fail to associate with Nup358 (Figs 5 and 6) and enter the nucleus independently of KIF5B (Fig 3) also activate cytoplasmic host cell sensors and initiate interferon response. 2016 PLoS pathogens Discussion HIV N74D;P90A 84;93 88;97 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Notably, nuclear entry of the N74D and P90A virus has previously been shown to be Nup358 independent. 2016 PLoS pathogens Discussion HIV N74D;P90A 30;39 34;43 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. Specifically, we observed that mutations which disrupt the hydrophobic binding pocket in assembled CA (N74D) and mutations which disrupt the conserved Cyp binding loop on CA (P90A) both perturb the relocalization of Nup358 induced by HIV-1 infection (Fig 4) and the association of CA and Nup358 during infection (Figs 5 and 6). 2016 PLoS pathogens Discussion HIV N74D;P90A 103;175 107;179 Capsid;Capsid;Capsid 99;171;281 101;173;283 HIV infections 234 249 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. The similarity in the results obtained following CPSF6 depletion and using the N74D mutant suggest a common mechanism. 2016 PLoS pathogens Discussion HIV N74D 79 83 27327622 KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. When the intensity of Nup358 staining associated with individual viral cores was measured, neither the N74D or P90A mutant exhibited significantly more colocalization with Nup358 than WT/DeltaEnv control virus (Fig 5), suggesting that both CA epitopes are required for Nup358 association. 2016 PLoS pathogens Discussion HIV N74D;P90A 103;111 107;115 Capsid 240 242 27333000 Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting. All studies reporting resistance mutations in this time period identified the reverse transcriptase M184V/I mutation. 2016 PloS one Discussion HIV M184I;M184V 100;100 107;107 RT 78 99 27333000 Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting. The patient had several mutations associated with drug resistance; however, only the M184V mutation was associated with FTC resistance. 2016 PloS one Discussion HIV M184V 85 90 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. Data from 211 adolescents in the United Kingdom exposed to ART showed 65% had mutations for NNRTIs, mainly K103N and Y181C, and 26% with mutations for PIs. 2016 International journal of environmental research and public health Discussion HIV K103N;Y181C 107;117 112;122 NNRTI;PI 92;151 98;154 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. It is one of the Thymidine Analog Mutations (TAMs), similarly to M41L, which is also a mutation conferring high level resistance to zidovudine, stavudine and some resistance to didanosine, abacavir and tenofovir. 2016 International journal of environmental research and public health Discussion HIV M41L 65 69 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. K103N is a nonpolymorphic mutation selected in patients receiving NVP and EFV. 2016 International journal of environmental research and public health Discussion HIV K103N 0 5 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. K103N mutation is in the reverse transcriptase gene region of HIV-1. 2016 International journal of environmental research and public health Discussion HIV K103N 0 5 RT 25 46 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. Similarly, M184V confers high-level resistance to lamivudine, and is a discriminatory mutation. 2016 International journal of environmental research and public health Discussion HIV M184V 11 16 27338425 Viral Suppression and Resistance in a Cohort of Perinatally-HIV Infected (PHIV+) Pregnant Women. V82A is a mutation also associated with protease inhibitor resistance in the HIV protease region. 2016 International journal of environmental research and public health Discussion HIV V82A 0 4 PR;PR 40;81 48;89 27343732 HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD). Nevertheless, because the Vpr A30L mutant was inactive in both NKR cells and MDDC (Fig.4), we suggest that Vpr should rescue the Env expression through a very similar mechanism. 2016 Virology Discussion HIV A30L 30 34 Vpr;Vpr;Env 26;107;129 29;110;132 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. 3.1%, p<0.0001), with a significant reduction in the frequency of M184V and of most thymidine analogue mutations (TAM), including D67N, K70R, L210W, T215F, T215Y, and K219E. 2016 PloS one Discussion HIV D67N;K219E;K70R;L210W;M184V;T215F;T215Y 130;167;136;142;66;149;156 134;172;140;147;71;154;161 27355626 Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. Increasing NNRTI TDR was associated with increasing K103N frequency in most sub-regions, although evidence of increasing frequency of nevirapine-selected mutations was also observed, particularly in the Caribbean, with significant increase of Y181C and G190A frequency. 2016 PloS one Discussion HIV G190A;K103N;Y181C 253;52;243 258;57;248 NNRTI 11 16 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. Here, we performed biochemical experiments and molecular modeling with the WT and the double-mutant (G140S-Q148H [SH]) that causes significant resistance to RAL and EVG and to a lesser extent to DTG. 2016 Nucleic acids research Discussion HIV G140S;Q148H 101;107 106;112 27369381 Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. This hypothesis is supported by the observation that the HIV-1 IN mutant Q146E has reduced 3'P activity (Figure 5). 2016 Nucleic acids research Discussion HIV Q146E 73 78 IN 63 65 27438849 Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications. Amino acid substitutions identified in Cameroon Tat sequences included N24K, N29K, and N40K respectively in 44%, 58%, and 30% of CRF02_AG samples and N24K in all subtype G samples. 2016 Viruses Discussion HIV N24K;N24K;N29K;N40K 71;150;77;87 75;154;81;91 Tat 48 51 27473196 Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV". HIV-1 clade C infection in South Africa revealed significant functional cognitive impairment that was independent of Tat (C31S) mutation, suggesting thereby that HIV-1 clade C could cause cognitive impairment similar to other HIV clades. 2016 Journal of neurovirology Discussion HIV C31S 122 126 Tat 117 120 HIV infections 0 23 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. Surprisingly, the AUC ratio of BiFC-INE11K+K186E containing E11K plus K186E substitutions switched the AAs located at E11 and K186 positions, restored to give the ratio of 0.93 as well as that of BiFC-INWT. 2016 Journal of virological methods Discussion HIV E11K;K186E;K186E 60;43;70 64;48;75 IN 36 38 27474494 Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization. When the potential utility of the current BiFC-IN system was further examined using the NCINIs, significant IN over-multimerization in the BiFC-IN system, well associated with the EC50 value of each NCINI, was observed to have occurred for all 3 NCINIs, while the A128T substitution-carrying IN showed less multimerization, demonstrating that the BiFC-IN system is useful for evaluating IN over-multimerization caused by NCINIs. 2016 Journal of virological methods Discussion HIV A128T 264 269 IN;IN;IN;IN;IN;IN 47;108;144;292;352;387 49;110;146;294;354;389 27476929 Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. The K65R mutation, which confers resistance to tenofovir, was rarely detected as a transmitted mutation, supporting previous work by our group suggesting that this should not affect the success of tenofovir-containing pre-exposure prophylaxis (PreP) if its use in the UK becomes more widespread 30. 2017 HIV medicine Discussion HIV K65R 4 8 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Based on the experiments performed so far, we can conclude that the L189F mutant remains structurally unchanged; hence, it may be the best candidate for use in experiments affecting the action of HIV-1 PR without causing structural alterations in the structure of the CA. 2016 FEBS open bio Discussion HIV L189F 68 73 Capsid;PR 268;202 270;204 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. In case of the L189F, W23A, A77P, and L189I mutants, these results are in agreement with results obtained from in silico analysis and CD measurements. 2016 FEBS open bio Discussion HIV A77P;L189F;L189I;W23A 28;15;38;22 32;20;43;26 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. On the other hand, A77P and L189P mutations caused inhibition of processing at the mutated sites, resulting in decreased CA degradation. 2016 FEBS open bio Discussion HIV A77P;L189P 19;28 23;33 Capsid 121 123 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Our results showed that CypA binding ability of W23A, A78V, L189F, L189I, and L189P mutants did not change significantly, while the A77P mutant showed a remarkable reduction in CypA binding. 2016 FEBS open bio Discussion HIV A77P;A78V;L189F;L189I;L189P;W23A 132;54;60;67;78;48 136;58;65;72;83;52 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Proteolysis at the cleavage sites containing W23A was substantially accelerated, leading to enhanced CA degradation. 2016 FEBS open bio Discussion HIV W23A 45 49 Capsid 101 103 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The A77P and L189P mutants were predicted to have a highly destabilizing effect on the protein structure, in line with the fact that proline is known to be a helix-breaker amino acid residue. 2016 FEBS open bio Discussion HIV A77P;L189P 4;13 8;18 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The A78V and L189F mutations also accelerated processing at the mutated sites, but with lack of enhanced or even decreased degradation, respectively. 2016 FEBS open bio Discussion HIV A78V;L189F 4;13 8;18 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The A78V, L189F, and L189I mutations were predicted to be neutral (L189I) or slightly destabilizing. 2016 FEBS open bio Discussion HIV A78V;L189F;L189I;L189I 4;10;21;67 8;15;26;72 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. The only exception is the W23A mutation, which was predicted to have only a slightly destabilizing effect, CD measurement, however, detected remarkable changes in the secondary structure of this mutant protein. 2016 FEBS open bio Discussion HIV W23A 26 30 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. Therefore, we have expressed and purified the wild-type and modified HIV-1 CA proteins (W23A, A77P, A78V, L189F, L189P, and L189I). 2016 FEBS open bio Discussion HIV A77P;A78V;L189F;L189I;L189P;W23A 94;100;106;124;113;88 98;104;111;129;118;92 Capsid 75 77 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. These predictions were confirmed by CD measurements: the secondary structure of A77P and L189P mutant capsid proteins showed remarkable alterations, while only slight deviations of the secondary structures were determined in case of A78V and L189F mutants, moreover, the distribution of secondary structural elements in L189I mutant closely resembled that of the wild-type capsid protein. 2016 FEBS open bio Discussion HIV A77P;A78V;L189F;L189I;L189P 80;233;242;320;89 84;237;247;325;94 Capsid;Capsid 102;373 108;379 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. This was an unexpected result as A77P falls outside of the Cyp binding region. 2016 FEBS open bio Discussion HIV A77P 33 37 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. We have found that the proteolytic susceptibility to trypsin did not change significantly in case of the A78V, L189F, and L189P mutants, while the W23A, A77P, and L189I mutants proved to be more prone to tryptic processing. 2016 FEBS open bio Discussion HIV A77P;A78V;L189F;L189I;L189P;W23A 153;105;111;163;122;147 157;109;116;168;127;151 27516963 Effect of internal cleavage site mutations in human immunodeficiency virus type 1 capsid protein on its structure and function. While W23A, A77P, and L189P mutations can effectively modify the proteolytic susceptibility of the CA; along with the so far observed structural alterations, they are not suitable for our goal. 2016 FEBS open bio Discussion HIV A77P;L189P;W23A 12;22;6 16;27;10 Capsid 99 101 27532886 Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials. Secondary integrase mutations(G140S/G and T97T/A) usually appeared together with Q148H/R and Y143Y/H. 2016 PloS one Discussion HIV G140G;G140S;Q148H;Q148R;T97A;T97T;Y143H;Y143Y 30;30;81;81;42;42;93;93 38;38;88;88;48;48;100;100 IN 10 19 27532886 Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials. The resistance of DTG mainly shown in 13 integrase mutations(including T97T/A, E138E/D, V151V/I, N155H, Q148, Y143C/H/R, T66A and E92Q). 2016 PloS one Discussion HIV E138D;E138E;E92Q;N155H;T66A;T97A;T97T;V151I;V151V;Y143C;Y143H;Y143R 79;79;130;97;121;71;71;88;88;110;110;110 86;86;134;102;125;77;77;95;95;119;119;119 IN 41 50 27532886 Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials. The ten major integrase mutations(including N155H, Y143C/R, Q148H/R, Y143Y/H, L74L/M, E92Q, E138E/A, Y143C, Q148Q and Y143S) could reduce the sensitivity of RAL and EVG. 2016 PloS one Discussion HIV E138A;E138E;E92Q;L74L;L74M;N155H;Q148H;Q148Q;Q148R;Y143C;Y143C;Y143H;Y143R;Y143S;Y143Y 92;92;86;78;78;44;60;108;60;101;51;69;51;118;69 99;99;90;84;84;49;67;113;67;106;58;76;58;123;76 IN 14 23 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. A final point is that, in contrast to the S40A mutation where much of the viral infectivity was maintained, the S40F mutation reduced the infectivity as shown here and previously yet the mutation was maintained in the infected host quasispecies. 2016 Retrovirology Discussion HIV S40A;S40F 42;112 46;116 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. A possible explanation for an advantage of the S40F mutation might be the formation of filopodia-like structures, a phenotype that was exhibited by that mutant. 2016 Retrovirology Discussion HIV S40F 47 51 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Consistent with this speculation, a highly resistant patient-derived strain also contains the same F56C mutation in the proximal cleavage site. 2016 Retrovirology Discussion HIV F56C 99 103 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. In participant #36, variants carrying the S40A mutation were the predominant variants detected in both vaginal fluid and plasma at the time of sampling. 2016 Retrovirology Discussion HIV S40A 42 46 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Interestingly, of all the possible nineteen other amino acid changes, we found only Ala and Phe (S40A and S40F, respectively) as substitutions for the Ser40 residue. 2016 Retrovirology Discussion HIV S40A;S40F 97;106 102;110 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. It is possible that the mutation was selected under pressure of ART after infection with virus that had S at Gagp6 position 40 or, alternatively, existed in the region and as a virus with the S40A already in it. 2016 Retrovirology Discussion HIV S40A 192 196 Gag 109 112 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. It of course will require more molecular and structural investigation to determine how the F56C mutation can regulate activities of the extended PRs while conferring drug resistance at the same time. 2016 Retrovirology Discussion HIV F56C 91 95 PR 145 148 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. It should be noted that although our study characterizes the virologic consequences of the S40A polymorphism detected in the HIV-1 variants that were obtained directly from the WIHS participants, the limitations imposed by the number of subjects examined and details of treatment prevent us from drawing direct conclusions about the effect of the mutations on susceptibility to the participant's treatment. 2016 Retrovirology Discussion HIV S40A 91 95 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. It should be noted that these extended PRs were also observed with the WT control but at low levels compared to the F56C construct. 2016 Retrovirology Discussion HIV F56C 116 120 PR 39 42 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Nevertheless, the S40A mutation impacted drug susceptibility. 2016 Retrovirology Discussion HIV S40A 18 22 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Our studies indicate that the Gag p6 S40A/Pol p6*-PR F56C mutation reduces mature PR production but enhances production, stability, and activity of extended forms of PR. 2016 Retrovirology Discussion HIV F56C 53 57 Pol;Gag;Gag;Gag;PR;PR;PR 42;30;34;46;50;82;166 45;33;36;48;52;84;168 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The F56C mutation somehow stabilizes the extended forms (both a and b forms) over a wide range of IDV concentrations. 2016 Retrovirology Discussion HIV F56C 4 8 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. The observed reduced production of mature PR due to the F56C mutation compared to the level made by the parental NL4-3 virus provides an explanation for the mutant's increased IDV resistance: Extended PR forms that are not the authentic target of the drug were generated instead of the mature PR. 2016 Retrovirology Discussion HIV F56C 56 60 PR;PR;PR 42;201;293 44;203;295 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Therefore, there might be something unique about the F56C mutation that not only permits it to stabilize the extended PR but also to enhance their proteolysis. 2016 Retrovirology Discussion HIV F56C 53 57 PR 118 120 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. This is consistent with results obtained in our previous study and herein where NL4-3 bearing the S40A mutation produced viral particles showing normal Gag processing and mature virion morphology. 2016 Retrovirology Discussion HIV S40A 98 102 Gag 152 155 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. This suggests that both S40A, which impacts PR, and S40F, which does not, provide a fitness advantage. 2016 Retrovirology Discussion HIV S40A;S40F 24;52 28;56 PR 44 46 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. We examined this possibility and found that, indeed, the infectivity defect of the S40F mutant was rescued by cell-to-cell transmission (Additional file 2: Figure S2). 2016 Retrovirology Discussion HIV S40F 83 87 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. We noticed that only F56C-containing enzymes demonstrated enhanced trans processing efficiency while the F56 V control showed a much reduced trans processing efficiency. 2016 Retrovirology Discussion HIV F56C;F56V 21;105 25;110 27600154 The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. With the F56C mutation, the proximal site processing was suppressed and the distal site processing was slightly enhanced. 2016 Retrovirology Discussion HIV F56C 9 13 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Autologous virus in each of the three family members also shared the same, rare, L188F mutation, which is strongly associated with HLA-B*81:01, and lies at the carboxy-terminus of the immunodominant HLA-B*81:01-restricted Gag epitope TL9 (TPQDLNTML, Gag 180-188). 2016 Retrovirology Discussion HIV L188F 81 86 Gag;Gag 222;250 225;253 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. For example, T190I and not T190A was able to compensate for T186S in the SK-254 virus but the reverse was the case in the SK-254(M) virus. 2016 Retrovirology Discussion HIV T186S;T190A;T190I 60;27;13 65;32;18 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. However, on the basis that low fitness viruses are less likely to be transmitted, the most parsimonious interpretation of these data may be that the fully compensated L188F virus was transmitted in both cases and that slow progression in the two children was not related to viral factors but to undefined host-specific factors. 2016 Retrovirology Discussion HIV L188F 167 172 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. If this were the case, it is likely that the virus transmitted by GD without L188F would have had normal viral replicative capacity, at least on the basis of the otherwise unremarkable gag sequence in these three family members. 2016 Retrovirology Discussion HIV L188F 77 82 Gag 185 188 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. In common with the more frequent HLA-B*81:01-TL9 escape mutation T186S, the L188F variant almost completely prevented viral replication when introduced into heterologous HIV strains. 2016 Retrovirology Discussion HIV L188F;T186S 76;65 81;70 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. In the more likely scenario of the virus encoding L188F being transmitted both to GD and D2, the fact that this virus was fully compensated in GD suggests that low viral replicative capacity is unlikely to have contributed to slow progression in the two children. 2016 Retrovirology Discussion HIV L188F 50 55 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. It is possible therefore that the same L188F variant within the B*81:01-TL9 epitope was selected independently from the wildtype TL9 sequence in all three family members subsequent to transmission, since all three individuals expressed HLA-B*81:01. 2016 Retrovirology Discussion HIV L188F 39 44 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. It remains entirely possible (as discussed further below) that either the uncompensated L188F variant was transmitted to both daughters, or that wildtype virus was transmitted and L188F plus the near-identical compensatory mutants were selected independently post-transmission in GM, GD and D2. 2016 Retrovirology Discussion HIV L188F;L188F 88;180 93;185 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Previous studies of the mutations selected within the HLA-B*81-TL9 epitope have similarly shown that the most frequent escape variant, T186S, can virtually abrogate viral replication. 2016 Retrovirology Discussion HIV T186S 135 140 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. Similar to the analyses reported here, the impact of T186S on viral replicative capacity varied considerably according to the nature of the viral backbone, as did the ability of variants such as T190I to rescue the virus from the fitness cost resulting from T186S. 2016 Retrovirology Discussion HIV T186S;T186S;T190I 53;258;195 58;263;200 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. The p24 Gag residues that might contribute to the substantial influence of sequence context on the impact of the TL9 escape mutants on viral replicative capacity observed here include several that have been previously implicated as compensatory mutants, such those within the cyclophilin A binding loop (V218A, H219Q and M228T), and the Gag tropism-determining loops (Gag residues 137-147; and Gag 248-254). 2016 Retrovirology Discussion HIV H219Q;M228T;V218A 311;321;304 316;326;309 p24;Gag;Gag;Gag;Gag 4;8;337;368;394 7;11;340;371;397 27608713 Paediatric non-progression following grandmother-to-child HIV transmission. The studies described here are highly consistent with these findings, in demonstrating, first, the dramatic negative impact of L188F, as well as T186S, on viral replicative capacity; and, second, the striking influence of viral sequence context. 2016 Retrovirology Discussion HIV L188F;T186S 127;145 132;150 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. A similar study from Asia found multi-NRTI resistant associated mutations (RAMs) in 37% of the patients, wherein, multi-NRTI RAMs were defined as presence of either Q151M; 69Ins; 2 TAMs; or M184V + 1 TAM. 2016 Medicine Discussion HIV M184V;Q151M 190;165 195;170 NRTI;NRTI 38;120 42;124 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Due to low prevalence of multi drug mutation such as T69Ins or Q151M, we adopted criteria for multi-NRTI DRMs as either presence of K65R or presence of 2 TAMs along with M184V or presence of 3 or more TAMs. 2016 Medicine Discussion HIV K65R;M184V;Q151M 132;170;63 136;175;68 NRTI 100 104 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. In a recent study from South Africa, authors have concluded that patients failing on a TDF-containing regimen were almost 5 times more likely to present with a K65R mutation compared to d4T-exposed patients. 2016 Medicine Discussion HIV K65R 160 164 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. In addition, recent reports have suggested antagonism between K65R and TAMs, indicating that both pathways are unlikely to occur simultaneously. 2016 Medicine Discussion HIV K65R 62 66 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. In presence of TAMs, M184V also causes additional low-level resistance to DDI and ABC. 2016 Medicine Discussion HIV M184V 21 26 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. In this study, 52.94% of individuals who were exposed to TDF-developed K65R mutation. 2016 Medicine Discussion HIV K65R 71 75 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. The emergence of K65R among individuals failing TDF-based regimen is primarily responsible for multi-NRTI resistance. 2016 Medicine Discussion HIV K65R 17 21 NRTI 101 105 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. The lower genetic barrier in subtype C for K65R may be attributed to enzymatic pausing arising at the end of poly-adenine stretches. 2016 Medicine Discussion HIV K65R 43 47 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. The most common NRTI mutations reported were M184V and K65R whereas K103N/S and V106A/M were common NNRTI resistance mutations. 2016 Medicine Discussion HIV K103N;K103S;K65R;M184V;V106A;V106M 68;68;55;45;80;80 75;75;59;50;87;87 NNRTI;NRTI 100;16 105;20 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. The selection of K65R is known to be facilitated in subtype C, which is a predominant circulating subtype in India. 2016 Medicine Discussion HIV K65R 17 21 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. The study highlights the importance of AZT as preferred NRTI option in second-line ART due to selection of K65R by TDF. 2016 Medicine Discussion HIV K65R 107 111 NRTI 56 60 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. Though TDF-based regimen is associated with higher rate of viral suppression as compared to AZT, one must be cautious of the emergence of K65R mutation among individuals failing TDF-based regimen. 2016 Medicine Discussion HIV K65R 138 142 27631260 Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India. With recent introduction of fixed-dose combination of TDF, 3TC, and EFV in national program, the emergence of K65R need to be monitored closely among HIV-1 subtype C-infected Indian population. 2016 Medicine Discussion HIV K65R 110 114 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Furthermore, DTG selected for more resistance substitutions (M50I, S119R, and R263K with a transient S153Y) with higher cross-resistance to EVG and RAL than BIC, which selected for M50I and R263K. 2016 Antimicrobial agents and chemotherapy Discussion HIV M50I;M50I;R263K;R263K;S119R;S153Y 61;181;78;190;67;101 65;185;83;195;72;106 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. In our site-directed mutant analysis, we confirmed that addition of M50I to R263K only showed a modest reduction in susceptibility to BIC over R263K alone while having no effect on susceptibility to DTG. 2016 Antimicrobial agents and chemotherapy Discussion HIV M50I;R263K;R263K 68;76;143 72;81;148 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. M50I and H51Y are two commonly observed secondary mutations associated with the primary mutation R263K during in vitro selection with DTG. 2016 Antimicrobial agents and chemotherapy Discussion HIV H51Y;R263K;M50I 9;97;0 13;102;4 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. On their own, neither mutation confers resistance to DTG, but in combination with R263K they moderately increase the resistance of R263K. 2016 Antimicrobial agents and chemotherapy Discussion HIV R263K;R263K 82;131 87;136 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. S153Y on its own confers greater resistance to BIC, DTG, and EVG than M50I or S119R but does not appear to be a secondary mutation to R263K, since no clone containing the S153Y/R263K double mutant was observed. 2016 Antimicrobial agents and chemotherapy Discussion HIV M50I;R263K;R263K;S119R;S153Y;S153Y 70;134;177;78;171;0 74;139;182;83;176;5 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Similar to M50I, S119R on its own confers almost no resistance to DTG or BIC, but in combination with R263K it has an effect comparable to that of M50I. 2016 Antimicrobial agents and chemotherapy Discussion HIV M50I;M50I;R263K;S119R 11;147;102;17 15;151;107;22 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. The Y143R single mutant in our panel has no effect on susceptibility to BIC or DTG and is mildly resistant to EVG but has a higher resistance to RAL. 2016 Antimicrobial agents and chemotherapy Discussion HIV Y143R 4 9 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. These included single mutants at positions E92, Y143, Q148, and N155, representing four principal resistance development pathways against RAL and EVG, and R263K, which is associated with DTG resistance, as well as double mutants comprising combinations of mutants at these major positions or with accessory mutations at positions E138 and G140. 2016 Antimicrobial agents and chemotherapy Discussion HIV R263K 155 160 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Viral clones engineered with the site-directed S153Y/R263K double mutant, although viable, were very difficult to grow, consistent with a reduced fitness relative to variants in drug-selected viral pools. 2016 Antimicrobial agents and chemotherapy Discussion HIV R263K;S153Y 53;47 58;52 27645238 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. While Y143R, Q148R, and N155H are primary RAL-associated mutations, E92Q is the most common initial mutation to emerge during failure of EVG-based regimens, followed by N155H and Q148R. 2016 Antimicrobial agents and chemotherapy Discussion HIV E92Q;N155H;N155H;Q148R;Q148R;Y143R 68;24;169;13;179;6 72;29;174;18;184;11 27648839 HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release. This TSG101 counteracting effect of Vpr did not occur as efficiently when using Vpr A30F mutant which is defective in Gag binding and Gag-mediated Vpr virion incorporation. 2016 PloS one Discussion HIV A30F 84 88 Vpr;Vpr;Vpr;Gag;Gag 36;80;147;118;134 39;83;150;121;137 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. A potential alternative explanation, however, could be that the mutation of K103N/Y188F might induce conformational changes that are distinct from K103N:yet still limit the access of NNRTIBP by NNRTIs:causing the same extent of resistance. 2016 Viruses Discussion HIV K103N;K103N;Y188F 76;147;82 81;152;87 NNRTI 194 200 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. For example, the K103A and K103E variants displayed better replication capacity than the WT virus. 2016 Viruses Discussion HIV K103A;K103E 17;27 22;32 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Glutamic acid substitution (K103E), on the other hand, is more easily deprotonated under neutral pH conditions. 2016 Viruses Discussion HIV K103E 28 33 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. If NNRTIs bind to the RT apo form before the RT binds to the primer-template, removal of the hydrogen bonding with K103N/Y188F substitutions should allow the NNRTIs to enter the NNRTIBP of the mutant in a similar fashion to WT; thus regaining the same extent of sensitivity to NNRTIs as the WT. 2016 Viruses Discussion HIV K103N;Y188F 115;121 120;126 NNRTI;NNRTI;NNRTI;RT;RT 3;158;277;22;45 9;164;283;24;47 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. In contrast, the Y181F, Y188F, or Y181F/Y188F mutant reduces the replication capacity significantly:especially the Y181F/Y188F double mutant:which suggests that the hydroxyl group in tyrosine may play a role in the reverse transcription process. 2016 Viruses Discussion HIV Y181F;Y181F;Y181F;Y188F;Y188F;Y188F 17;34;115;24;40;121 22;39;120;29;45;126 RT 215 236 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. In summary, results from this study suggest that the hydrogen bond between K103N and Y188 may not play an important role in the resistance of the K103N mutant to NNRTIs. 2016 Viruses Discussion HIV K103N;K103N 75;146 80;151 NNRTI 162 168 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Interestingly, the double mutant Y181F/Y188F uniformly increases the sensitivity to NNRTI inhibition. 2016 Viruses Discussion HIV Y181F;Y188F 33;39 38;44 NNRTI 84 89 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. K103A and K103E mutant viruses displayed similar levels of susceptibility to the NNRTIs, and the respective mutant RTs only showed low levels of resistance (<5-fold) to the NNRTIs in the biochemical assay. 2016 Viruses Discussion HIV K103E;K103A 10;0 15;5 NNRTI;NNRTI;RT 81;173;115 87;179;118 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Otherwise, by shortening the length of the aliphatic side chain at 103 with K103A or K103E substitution, this should also significantly reduce the binding affinity of NNRTIs to the two mutants to the same extent as to the K103N substitution. 2016 Viruses Discussion HIV K103A;K103E;K103N 76;85;222 81;90;227 NNRTI 167 173 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. Rather, the resistance may come from differences in the electrostatic interactions with NNRTIs between K103N and the WT because the free amino group in lysine is more easily protonated, compared with the amide group in asparagine. 2016 Viruses Discussion HIV K103N 103 108 NNRTI 88 94 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The fact that the resistance level of K103N and K103N/Y188F mutant viruses and RTs to the NNRTIs are comparable in both cell-based and biochemical assays strongly suggests that the hydrogen bond between K103N and Y188 may not play an important role in the resistance of K103N substitution to respective NNRTIs. 2016 Viruses Discussion HIV K103N;K103N;K103N;K103N;Y188F 38;48;203;270;54 43;53;208;275;59 NNRTI;NNRTI;RT 90;303;79 96;309;82 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. The hydrogen bond between N103 and Y188, observed in the X-ray structure of unliganded K103N RTs, may be interrupted, or significantly weakened, upon the formation of a tertiary complex of K103N RT-primer-template:because it is known that RTs undergo significant conformational changes after binding to the primer and template. 2016 Viruses Discussion HIV K103N;K103N 87;189 92;194 RT;RT;RT 93;195;239 96;197;242 27669286 Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor-Resistant Mutations with K103N and Y181C Substitutions. These findings suggest that the resistance of K103N (>30 fold) may not be owing to the lower level of hydrophobic interactions by the change of lysine to asparagine (from four carbons to one carbon). 2016 Viruses Discussion HIV K103N 46 51 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. A previous study suggested that I37K in the HR1 interferes with the binding of C34 and that N126K in the HR2 enhances the intra-gp41 binding of HR1 and HR2 compared with C34. 2016 Retrovirology Discussion HIV I37K;N126K 32;92 36;97 gp41 128 132 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Additionally, the sensitivity to sCD4 was higher for the I37K mutant than it was for the N126K mutant. 2016 Retrovirology Discussion HIV I37K;N126K 57;89 61;94 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Another effect of gp41 mutations was reduced viral infectivity and envelope content especially for mutants bearing I37K mutation. 2016 Retrovirology Discussion HIV I37K 115 119 Env;gp41 67;18 75;22 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Anti-CD4bs antibodies 42F9 and 49G2 bound to the I37K mutant better than they did to the N126K mutant, even though the neutralization sensitivities of these mutants to anti-CD4bs antibodies were similar. 2016 Retrovirology Discussion HIV I37K;N126K 49;89 53;94 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. As mentioned earlier, I37K and N126K mutations enhanced the neutralization sensitivity compared with that of WT; however, this effect was antagonized by the combination of I37K and N126K mutations. 2016 Retrovirology Discussion HIV I37K;I37K;N126K;N126K 22;172;31;181 26;176;36;186 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Furthermore, compared with the WT, the N126K mutant has improved neutralization sensitivity to CD4bs MAbs. 2016 Retrovirology Discussion HIV N126K 39 44 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Hence, in addition to I37K and N126K, L204I likely also has functional importance. 2016 Retrovirology Discussion HIV I37K;L204I;N126K 22;38;31 26;43;36 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. However, occurrence of N126K mutation has been observed in ENF-treated patients, suggesting that these mutations conferring resistance to C34 derivative fusion inhibitors may arise in HIV-1-infected patients. 2016 Retrovirology Discussion HIV N126K 23 28 HIV infections 184 198 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. However, pseudoviruses containing both I37K and N126K mutations showed neutralization sensitivities that are similar to those of WT. 2016 Retrovirology Discussion HIV I37K;N126K 39;48 43;53 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. It is possible that N126K may reduce other structural interference to epitope access on the virion surface during the viral entry step. 2016 Retrovirology Discussion HIV N126K 20 25 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Notably, the tier 2 virus JR-FL mutants containing a single mutation of I37K or N126K in gp41 could both be neutralized by antibodies 42F9 and 49G2, which target CD4bs, even though these antibodies were thought to only be capable of neutralizing tier 1 strains. 2016 Retrovirology Discussion HIV I37K;N126K 72;80 76;85 gp41 89 93 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Of the antibodies we tested, a single L204I substitution appeared to only affect the neutralization sensitivity to the anti-V3 antibody 16G6. 2016 Retrovirology Discussion HIV L204I 38 43 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Our neutralization assay data show that I37K is the key mutation for the observed enhancement in neutralization sensitivity. 2016 Retrovirology Discussion HIV I37K 40 44 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Our study reveals that the I37K mutation can increase the structural fluctuations of gp41 protomers, prominently those in the regions corresponding to the gp41-gp120 interfaces in Env trimer. 2016 Retrovirology Discussion HIV I37K 27 31 gp120;gp41;gp41;Env 160;85;155;180 165;89;159;183 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The effect of I37K, which exposes epitopes for neutralization, may be countered by N126K, which stabilizes the gp41 structure by enhancing the binding of HR1 and HR2. 2016 Retrovirology Discussion HIV I37K;N126K 14;83 18;88 gp41 111 115 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The L204I mutation is one of the three mutations in C34r, and this mutation is commonly observed in variants that are resistant to C34 derivatives (Additional file 1. 2016 Retrovirology Discussion HIV L204I 4 9 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The L204I mutation significantly contributed to neutralization sensitivity when it was combined with other C34-resistance-associated mutations, I37K and N126K. 2016 Retrovirology Discussion HIV I37K;L204I;N126K 144;4;153 148;9;158 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The mutations obtained by in vitro passages, especially I37K, which has significantly decreased infectivity, may be disadvantageous to viral replication in vivo. 2016 Retrovirology Discussion HIV I37K 56 60 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The results of a molecular dynamic simulation support the effect of I37K mutation on enhanced neutralization sensitivity, which is indicated by a fluctuation of the gp41 trimer structure. 2016 Retrovirology Discussion HIV I37K 68 72 gp41 165 169 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. The results of flow cytometry analyses of antibody binding indicate that I37K and N126K mutations have different impacts on untriggered cell surface envelope proteins. 2016 Retrovirology Discussion HIV I37K;N126K 73;82 77;87 Env 149 157 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. These results suggest that the I37K mutation may change the Env structure to an open conformation, in which antibodies can access the epitopes that are hidden inside in the closed conformation. 2016 Retrovirology Discussion HIV I37K 31 35 Env 60 63 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. They found that anti-MPER antibodies enhanced the neutralization sensitivity of YU-2 containing the ENF-resistance-conferring mutations G36D or V38 M. 2016 Retrovirology Discussion HIV G36D;V38M 136;144 140;149 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. This indicates that the I37K and N126K mutations antagonize the effects on neutralization sensitivity of each other. 2016 Retrovirology Discussion HIV I37K;N126K 24;33 28;38 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. Unfortunately, the mechanism by which the N126K mutation enhances neutralization sensitivity is unclear. 2016 Retrovirology Discussion HIV N126K 42 47 27670680 Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. We have identified I37K in the HR1 region of gp41 as a key mutation for C34 resistance, for the exposure of gp120 epitopes, and for slowing down the fusion process, resulting in enhanced neutralization sensitivity of variants with this mutation. 2016 Retrovirology Discussion HIV I37K 19 23 gp120;gp41 108;45 113;49 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. An interesting observation in this study was that V179D/E, an NNRTI-associated mutation was dominating Shanghai MSM. 2016 Scientific reports Discussion HIV V179D;V179E 50;50 57;57 NNRTI 62 67 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. Besides, we found a higher proportion of V179D/E mutation in Shanghai CRF01_AE strains than in all others China CRF01_AE strains. 2016 Scientific reports Discussion HIV V179D;V179E 41;41 48;48 27698457 Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China. Sequences with V179D/E were distributed and networked in most sub-lineages in SH-L1, suggesting that several independent CRF01_AE strains with V179D/E were involved in ongoing transmission in this city. 2016 Scientific reports Discussion HIV V179D;V179D;V179E;V179E 15;143;15;143 22;150;22;150 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. In our studies, the I143T increased host cell entry efficiency. 2016 Virology Discussion HIV I143T 20 25 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. In the m165-05 macaque, the appearance of the E32K mutation coincided with rapid virus evolution, slow declines in CD4 T cells, and continual HIV-1 replication despite significant antibody and CTL responses. 2016 Virology Discussion HIV E32K 46 50 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. In the SOSIP gp140 structure, I143T, N148S, and S151G mutations are located within a disordered V1 loop (Fig 8A and C, highlighted in blue). 2016 Virology Discussion HIV I143T;N148S;S151G 30;37;48 35;42;53 gp140 13 18 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Lack of prolonged CD4 cell declines in these 4 macaques infected with SHIV_KB9-B3m165-05d21 indirectly suggest that E32K may be the necessary change for this pathogenicity. 2016 Virology Discussion HIV E32K 116 120 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Most of these mutations reverted to wild type B3 sequence during m165-05 infection except for the E32K mutation that increased in the quasispecies and became fixed by day 98. 2016 Virology Discussion HIV E32K 98 102 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Overall, we did not observe an overlap of the V1 mutations or E32K with the binding sites for other neutralizing antibodies 8ANC195, 35O22, and PGT122 (Fig 8B,C,&D) . 2016 Virology Discussion HIV E32K 62 66 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. SHIV's with this deletion persisted in m165-05 but were eventually replaced by day 143 with the I143T, N148S, S151G mutations in the V1 domain. 2016 Virology Discussion HIV I143T;N148S;S151G 96;103;110 101;108;115 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The E32K mutation found in the C1 Env domain was linked to HIV-like pathogenesis and appears to stabilize the gp120-gp41 interaction in this SHIVenv construct. 2016 Virology Discussion HIV E32K 4 8 gp120;gp41;Env 110;116;34 115;120;37 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The E32K mutation has now been introduced into SHIV_KB9-B3m165-05d21 and macaque infection studies are underway. 2016 Virology Discussion HIV E32K 4 8 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The E32K mutation is the only dominant mutation that emerged in the SHIVenvB3 of m165-05 aside from those in the V1 domain. 2016 Virology Discussion HIV E32K 4 8 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The factors contributing to SHIVenv_B3 pathogenesis in outbred Indian Rhesus macaques is complicated but could be related to the appearance of the E32K mutations in SHIVenv_B3. 2016 Virology Discussion HIV E32K 147 151 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. The I143T mutation may have an effect on antibody binding due to the shorter side chain, and the addition of a hydroxyl group on the threonine (depending on the orientation of this "flexible" loop region). 2016 Virology Discussion HIV I143T 4 9 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Ultimately, the E32K mutation may be necessary for SHIV survival and pathogenesis in Rhesus macaques. 2016 Virology Discussion HIV E32K 16 20 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. Unfortunately, we only discovered the presence of E32K following studies on the infection/pathogenicity of cloned SHIV_KB9-B3m165-05d21 from SHIV found at day 21 in m165-05 (lacking E32K). 2016 Virology Discussion HIV E32K;E32K 50;182 54;186 27723488 Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. We propose that E32K mutations would enhance electrostatic interactions with the D618/D619 in gp41, stabilize the trimer structure, and may even enhance SHIV entry and replicative fitness. 2016 Virology Discussion HIV E32K 16 20 gp41 94 98 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Also of interest, a large cluster of patients with the E138A mutation was observed, including both females and males (MSM and heterosexual). 2016 PloS one Discussion HIV E138A 55 60 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Although it is true that part of the increasing trend in PDR was due to an increasing trend observed in E138A frequency (Fig 5), affecting RPV and ETR (drugs not used in Nicaragua), PDR to the two most common first-line ART regimens in Nicaragua reached important levels in 2015: 14.6% to AZT + 3TC + EFV and 10.4% to TDF + FTC + EFV. 2016 PloS one Discussion HIV E138A 104 109 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. In all, these observations suggest long-term stability of E138A, and that E138A spread may be associated to founder effects rather than increasing transmission from persons with ADR. 2016 PloS one Discussion HIV E138A;E138A 58;74 63;79 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. In most cases, the presence of E138A was not associated with other low-abundance DR variants. 2016 PloS one Discussion HIV E138A 31 36 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. In only two cases, this mutation was accompanied by other DR variants within 5%-10% frequency: K101E and K219Q. 2016 PloS one Discussion HIV K101E;K219Q 95;105 100;110 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. In the present study, E138A frequency was 4.2% using Sanger sequencing. 2016 PloS one Discussion HIV E138A 22 27 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. In this work, we found the M41L mutation in 16 viruses sequenced with NGS; 10 of them were included in transmission clusters and 14 had the mutation in proportions over 90%, while two presented it as a low-abundance variant under the 5% threshold. 2016 PloS one Discussion HIV M41L 27 31 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Indeed, viruses with PDR sequenced from RI persons included mainly one of three DRMs: M41L, K103N, or E138A. 2016 PloS one Discussion HIV E138A;K103N;M41L 102;92;86 107;97;90 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Interestingly, a large cluster of MSM with a singleton M41L mutation was identified. 2016 PloS one Discussion HIV M41L 55 59 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Only four of the patients with M41L (all with long-standing infection) also presented other low-abundance DR variants (<5%): K103N, Y181C, K65R, and PR G73S. 2016 PloS one Discussion HIV G73S;K103N;K65R;M41L;Y181C 152;125;139;31;132 156;130;143;35;137 PR 149 151 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Previous work supports the stability and lack of reversion of this mutation, as well as long-term circulation of some TAMs, including M41L, without the presence of low-abundance variants contributing with more extensive resistance. 2016 PloS one Discussion HIV M41L 134 138 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. The fact that M41L was more frequent in RI persons could be thus explained mostly by founder effects and MSM transmission networks, more than by acquisition of viruses with ADR and later reversion of other mutations. 2016 PloS one Discussion HIV M41L 14 18 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. The most common SDRMs responsible for this PDR prevalence were K103N and M41L. 2016 PloS one Discussion HIV K103N;M41L 63;73 68;77 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. These observations support the long-term circulation of M41L, as well as the possibility of transmission from individuals with PDR rather than from individuals with ADR directly. 2016 PloS one Discussion HIV M41L 56 60 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. This PDR definition considers the effect of the polymorphic mutation E138A, which together with other accessory mutations increase NNRTI PDR prevalence estimations, affecting mainly RPV susceptibility. 2016 PloS one Discussion HIV E138A 69 74 NNRTI 131 136 27736898 HIV Drug Resistance in Antiretroviral Treatment-Naive Individuals in the Largest Public Hospital in Nicaragua, 2011-2015. Using NGS, a total of 13 patients presented the E138A mutation over the 20% threshold and 10 additional patients presented E138 mutants as low-abundance variants <20%, including E138A, E138K and E138G. 2016 PloS one Discussion HIV E138A;E138A;E138G;E138K 48;178;195;185 53;183;200;190 27737691 An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating. The HIV-1 CA mutant G89V is insensitive to the effect of TRIM11, which strengthened the possibility that the capsid of HIV-1 could be the determinant for restriction by TRIM11. 2016 Retrovirology Discussion HIV G89V 20 24 Capsid;Capsid 109;10 115;12 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. HIV-2 Env N659D virus is therefore unable to antagonize BST-2 and does not promote the endocytosis and sequestration of BST-2. 2016 Viruses Discussion HIV N659D 10 15 Env 6 9 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Interestingly, we demonstrated that only a single substitution of the asparagine in position 659 (Env N659D) markedly impaired the viral release ability compared to the HIV-2 ROD wild type virus in two different T lymphocytes cell lines. 2016 Viruses Discussion HIV N659D 102 107 Env 98 101 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. Subtilisin treatment revealed that the HIV-2 Env N659D virus was eleven-fold more tethered at the cell surface than HIV-2 Env WT or Env 1-749 viruses and thus presented an inability to be released from H9 cells. 2016 Viruses Discussion HIV N659D 49 54 Env;Env;Env 45;122;132 48;125;135 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. The N659D substitution could potentially have an impact on the HIV-2 predicted MPER functions. 2016 Viruses Discussion HIV N659D 4 9 27754450 Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. This key experiment indicated that the viral replication and release of the Env N659D virus were restored to a comparable level as with the wild type virus. 2016 Viruses Discussion HIV N659D 80 85 Env 76 79 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Among the 6 strains with Y143R mutations, 4 had T97A, which has been shown to increase Y143R/C-mediated resistance to raltegravir. 2016 Scientific reports Discussion HIV T97A;Y143C;Y143R;Y143R 48;87;25;87 52;94;30;94 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Besides the Q148 mutation combined with one or more of G140A/C/S, L74I and E138A/K/T was identified to reduce viral susceptibility to dolutegravir, two amino acid mutations, G118R and R263K, have been reported to confer low-level resistance to dolutegravir. 2016 Scientific reports Discussion HIV E138A;E138K;E138T;G118R;G140A;G140C;G140S;L74I;R263K 75;75;75;174;55;55;55;66;184 84;84;84;179;64;64;64;70;189 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Different from previous studies, we did not find significant association of L74M and G163R with raltegravir exposure and the prevalence of P145R was significantly higher in the strains from INSTI-naive patients than those from raltegravir-experienced patients. 2016 Scientific reports Discussion HIV G163R;L74M;P145R 85;76;139 90;80;144 INSTI 190 195 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Except E92Q, the amino acid substitutions in the parenthesis representing the compensatory mutations that can help restore fully or partly viral fitness. 2016 Scientific reports Discussion HIV E92Q 7 11 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. However, some of the mutations are significantly associated with raltegravir exposure, such as L74M, T97A, E138K, V151I and G163R. 2016 Scientific reports Discussion HIV E138K;G163R;L74M;T97A;V151I 107;124;95;101;114 112;129;99;105;119 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. In INSTI-naive patients, we observed that 0.7% of the sequences (N = 9) harboured the N155S/T mutation, which was not observed in any of the raltegravir-experienced patients in our study. 2016 Scientific reports Discussion HIV N155S;N155T 86;86 93;93 INSTI 3 8 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. In our study, we also found that the prevalence of T97A, G140CAS, E157Q, or V151I was all significantly higher in HIV-1 strains from raltegravir-experienced patients than those from INSTI-naive patients (Supplementary Table 3). 2016 Scientific reports Discussion HIV E157Q;G140A;G140C;G140S;T97A;V151I 66;57;57;57;51;76 71;64;64;64;55;81 INSTI 182 187 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. In our study, we did not identify any G118R substitution in our specimens, yet the prevalence of R263K was 0.31% and 1.64% in INSTI-naive and raltegravir-experienced patients, respectively. 2016 Scientific reports Discussion HIV G118R;R263K 38;97 43;102 INSTI 126 131 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. In patients experiencing virological failure to the first generation of INSTIs, raltegravir and elvitegravir, three genotypic mutation pathways have been defined: Q148H/R/K (+-G140S or E138A/K), N155H (+-E92Q), and Y143C/H/R (+-T97A). 2016 Scientific reports Discussion HIV E138A;E138K;E92Q;G140S;N155H;Q148H;Q148K;Q148R;T97A;Y143C;Y143H;Y143R 185;185;204;176;195;163;163;163;228;215;215;215 192;192;208;181;200;172;172;172;232;224;224;224 INSTI 72 78 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. In the 12 sequences with the Q148H mutation, all had G140S mutation, the predominant combination of INSTI-related resistance mutations as observed in raltegravir-experienced patients by Fourati et al. 2016 Scientific reports Discussion HIV G140S;Q148H 53;29 58;34 INSTI 100 105 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. N155S was first identified by in vitro passage experiment in the presence of raltegravir, and it has never been reported in sequences from patients receiving raltegravir. 2016 Scientific reports Discussion HIV N155S 0 5 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Of 30 subjects who failed INSTI-containing regimens in this study, 17 had Q148H/K/R mutations, 8 had N155H mutations, and 6 had Y143C/H/R mutations. 2016 Scientific reports Discussion HIV N155H;Q148H;Q148K;Q148R;Y143C;Y143H;Y143R 101;74;74;74;128;128;128 106;83;83;83;137;137;137 INSTI 26 31 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. One of them, patient 4562, was naive to raltegravir treatment and was likely to acquire Q148H/K/R mutation from his partner, patient 4563, who had failed to respond to raltegravir-containing regimen with HIV-1 harbouring Q148H/K/R mutation. 2016 Scientific reports Discussion HIV Q148H;Q148H;Q148K;Q148K;Q148R;Q148R 88;221;88;221;88;221 97;230;97;230;97;230 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Our study provides the first evidence that Q148H/K/R mutation can be transmitted from patients who failed raltegravir-containing regimens to raltegravir-naive patients. 2016 Scientific reports Discussion HIV Q148H;Q148K;Q148R 43;43;43 52;52;52 27779200 Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan. Whether the presence of N155S/T only in INSTI-naive patients implicates its better transmissibility than N155H mutant viruses requires future investigations. 2016 Scientific reports Discussion HIV N155H;N155S;N155T 105;24;24 110;31;31 INSTI 40 45 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. K103N causes high-level resistance to NVP and EFV and Y181C can cause high-level resistance to NVP and intermediate resistance to EFV. 2016 BioMed research international Discussion HIV Y181C;K103N 54;0 59;5 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. K103N, Y181C were the most prevalent mutations associated with NNRTI resistance in our study. 2016 BioMed research international Discussion HIV Y181C;K103N 7;0 12;5 NNRTI 63 68 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. M184V could cause high-level resistance to 3TC and low-level resistance to ddI. 2016 BioMed research international Discussion HIV M184V 0 5 27807537 Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. M41L belongs to TAMs (thymidine analogue-associated mutations) that were selected by AZT and D4T. 2016 BioMed research international Discussion HIV M41L 0 4 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. However, an A84V mutation was sufficient to markedly decrease Nef protein levels in high-expression strain B.JRFL Nef, while a V84A mutation was sufficient to restore Nef to detectable levels in low-expression strain C.BR92025 Nef. 2016 mSphere Discussion HIV A84V;V84A 12;127 16;131 Nef;Nef;Nef;Nef 62;114;167;227 65;117;170;230 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. However, in the context of strain B.JRFL Nef, the K92E mutation does not significantly impact function and expression. 2016 mSphere Discussion HIV K92E 50 54 Nef 41 44 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. Our mutational studies of strain C.BR92025 Nef suggest an important role for K92 in the function and expression of Nef, as the restorative E92K mutation partially rescues the function and expression of strain C.BR92025 Nef. 2016 mSphere Discussion HIV E92K 139 143 Nef;Nef;Nef 43;115;219 46;118;222 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. Specifically, W13 appears to be required for efficient MHC-I downregulation, as a W13R mutation significantly reduces the MHC-I downregulation efficiency of strain B.JRFL Nef, whereas an R13W mutation rescues the MHC-I downregulation efficiency of strain C.BR92025 Nef. 2016 mSphere Discussion HIV R13W;W13R 187;82 191;86 Nef;Nef 171;265 174;268 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. This hypothesis is supported by a tryptophan mutation (A84W) that introduces a large bulky residue and more severely disrupts Nef receptor downregulation. 2016 mSphere Discussion HIV A84W 55 59 Nef 126 129 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. This was supported by a W13A mutation that disrupted MHC-I downregulation and the ability of Nef to pull down AP-1 in vitro. 2016 mSphere Discussion HIV W13A 24 28 Nef 93 96 27840851 A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression. When an A84V mutation was introduced into strain B.JRFL Nef, its pulse-chase profile shifted to resemble that of strain C.BR92025 Nef, whereas a V84A mutation introduced into strain C.BR92025 Nef shifted its pulse-chase profile to resemble that of strain B.JRFL Nef. 2016 mSphere Discussion HIV A84V;V84A 8;145 12;149 Nef;Nef;Nef;Nef 56;130;192;262 59;133;195;265 27858889 Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study. In particular, K103N is a nonpolymorphic mutation selected in patients receiving nevirapine and efavirenz and able to reduce both nevirapine and efavirenz susceptibility by >=10 folds. 2016 Medicine Discussion HIV K103N 15 20 27858889 Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study. Mutations were the K103N in 1 case and the Y181C in the other case, both known to be major DRMs to NNRTI drugs, according to the Stanford database (http://hivdb.stanford.edu/). 2016 Medicine Discussion HIV K103N;Y181C 19;43 24;48 27858889 Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study. Y181C is a nonpolymorphic mutation described to reduce susceptibility to nevirapine by >50-folds. 2016 Medicine Discussion HIV Y181C 0 5 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Also, JRCSF may be more "native-like" than JRFL in that it efficiently binds to PG9/PGT145 class of bNAbs even better than JRFL (E168K). 2016 Retrovirology Discussion HIV E168K 129 134 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. Furthermore, JRCSF, which binds weakly to CD4-bs-directed antibodies, can be made to bind this class of bNAbs efficiently by incorporating the N197D mutation without disrupting its native conformation. 2016 Retrovirology Discussion HIV N197D 143 148 27871328 Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes. However, single amino acid mutations in V2 (N167D and K168E) did not abolish binding of JRCSF to V1V2 bNAbs. 2016 Retrovirology Discussion HIV K168E;N167D 54;44 59;50 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. HIV-1 harboring the N74D capsid change fails to interact with CPSF6 and evades this nuclear import restriction. 2016 Scientific reports Discussion HIV N74D 20 24 Capsid 25 31 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. However, the N74D mutant seems to be less sensitive to TNPO3 and Nup358/RANBP2 depletion and instead uses different nucleoporins like NUP155 to enter the nucleus. 2016 Scientific reports Discussion HIV N74D 13 17 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. In our study, we found that the N74D and, to a lesser degree, the V86M and H87Q capsid mutants escape the block present in marmoset B-LCLs. 2016 Scientific reports Discussion HIV H87Q;N74D;V86M 75;32;66 79;36;70 Capsid 80 86 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. The N74D mutant has been shown to enter the nucleus though an altered nuclear entry pathway that results in integration in genomic regions that are sparse in transcription units compared to WT viruses that integrate in gene-rich chromosomal regions. 2016 Scientific reports Discussion HIV N74D 4 8 27876849 Characterization of two distinct early post-entry blocks to HIV-1 in common marmoset lymphocytes. Thus, the use of a different nuclear entry pathway by the N74D mutant might contribute to the escape from the Lv4-like activity in the marmoset B-LCLs. 2016 Scientific reports Discussion HIV N74D 58 62 27897226 Viral and Host Characteristics of Recent and Established HIV-1 Infections in Kisumu based on a Multiassay Approach. For instance, V82I polymorphism in subtype G contributes to emergence of I82M/T/S resistance after protease inhibitor based treatment failure. 2016 Scientific reports Discussion HIV I82M;I82S;I82T;V82I 73;73;73;14 81;81;81;18 PR 99 107 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. A design for a stabilized p17 protein might be two combined mutations of E12L/H89F. 2016 PloS one Discussion HIV E12L;H89F 73;78 77;82 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. A less dynamic structure was unexpectedly detected through the entire molecule in E12A compared to in WT on the basis of the order parameter, heteronuclear NOE, and the average values of kex for quick amide proton exchanges. 2016 PloS one Discussion HIV E12A 82 86 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Another possible mechanism is that the structural changes induced by E12A altered the environments of H33 including solvent accessibility. 2016 PloS one Discussion HIV E12A 69 73 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Changes in local structure caused by the E12A mutation. 2016 PloS one Discussion HIV E12A 41 45 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Effects of pH on the dynamic structures of E12A. 2016 PloS one Discussion HIV E12A 43 47 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Finally, the average rate constants derived from the amide proton exchanges of the entire flexible regions were lower in E12A compared to WT. 2016 PloS one Discussion HIV E12A 121 125 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. For these reasons, the dynamics data for WT and E12A were recorded at the physiological condition of pH 7. 2016 PloS one Discussion HIV E12A 48 52 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Furthermore, differences in CA chemical shifts of E12A minus WT were mainly positive except in the mutated E12A region (Fig 2A), suggesting that a more helical structure was adopted in E12A compared to WT. 2016 PloS one Discussion HIV E12A;E12A;E12A 50;107;185 54;111;189 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Furthermore, it was shown that the structure fluctuated more in the helix 1 of E12A than in WT based on other dynamics experiments including the relaxation studies and amide proton exchange using T2 and heteronuclear NOE (Fig 3A and 3C) and CLEANEX-PM (Fig 3D). 2016 PloS one Discussion HIV E12A 79 83 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. However, since the H89A mutation led to a strong tendency for protein aggregation, the L85A mutant was designed and produced. 2016 PloS one Discussion HIV H89A;L85A 19;87 23;91 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In contrast, quick exchanges were observed at L75-Y79 (N-terminus of helix 4) in E12A at pH 5.5 (Fig 5D). 2016 PloS one Discussion HIV E12A 81 85 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In contrast, the values of the order parameters for E12A were relatively unchanged from helix 1 to 5, including the loop regions, and had higher values (Fig 4B) than those of WT. 2016 PloS one Discussion HIV E12A 52 56 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In particular, the long-range effects of the L85A mutation in helix 4 were observed as differences in the chemical shifts at R7-E12 in helix 1 (Fig 7A, 7B and 7C). 2016 PloS one Discussion HIV L85A 45 49 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. In this study using a CLEANEX-PM experiment, the amide protons, which are located in the loop regions, were focused on to compare the dynamic structures between E12A and WT. 2016 PloS one Discussion HIV E12A 161 165 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. It is possible that the location of helix 4 in E12A is slightly shifted at pH 5.5, based on the CLEANEX-PM data comparing pH 7 (Fig 3D) to 5.5 (Fig 5D). 2016 PloS one Discussion HIV E12A 47 51 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Next, we intended to destabilize the structure of E12A in order to observe the more disordered structure. 2016 PloS one Discussion HIV E12A 50 54 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. On the basis of both the chemical shift and CLEANEX-PM data, it was concluded that there could be no E12-H89 interaction in the L85A mutant (Fig 7) similar to that observed with the E12A mutant. 2016 PloS one Discussion HIV E12A;L85A 182;128 186;132 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. On the other hand, the significant effects of the E12A mutation on the chemical shifts for the region around H89 were observed at pH 7, indicating the E12-H89 interaction (Fig 2). 2016 PloS one Discussion HIV E12A 50 54 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Originally, we intended to prepare the H89A mutant. 2016 PloS one Discussion HIV H89A 39 43 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Quick exchanges corresponding to the alpha3-4 loop region were observed in CLEANEX-PM for both WT and E12A at pH 7 (Fig 3D). 2016 PloS one Discussion HIV E12A 102 106 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Secondly, the average value of heteronuclear NOE for the structured regions of E12A was greater than 0.8 (Fig 3C), whereas that for WT was less than 0.8. 2016 PloS one Discussion HIV E12A 79 83 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Stabilizing effect on the structure by E12A mutation. 2016 PloS one Discussion HIV E12A 39 43 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The aggregation, with the H89G mutant, has been previously reported. 2016 PloS one Discussion HIV H89G 26 30 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The amplitude of the value of DeltaG (H2O) of E12A was higher than that for WT. 2016 PloS one Discussion HIV E12A 46 50 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The changes in the chemical shifts observed at L8-A12, as well as V84-Q90, (Fig 2) were probably due to the loss of the electrostatic interaction like salt bridges, as well as hydrogen bonds between E12 and H89, caused by the E12A mutation. 2016 PloS one Discussion HIV E12A 226 230 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The chemical exchanges were probably due to the occurrence of conformational exchanges at the alpha1-2 loop and helix 5 regions in E12A. 2016 PloS one Discussion HIV E12A 131 135 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The differences of the chemical shifts of CA, CB, and CO between L85A and WT (Fig 7A, 7B and 7C) were similar to those observed between E12A and WT (Fig 2A, 2B and 2C). 2016 PloS one Discussion HIV E12A;L85A 136;65 140;69 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The E12A mutation abolished the formation of a p17 trimer, which may be due to the formation of a less flexible loop in structure. 2016 PloS one Discussion HIV E12A 4 8 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The E12A mutation did not cause a large structural change. 2016 PloS one Discussion HIV E12A 4 8 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The L85A mutation also caused other structural effects on regions including helix 2. 2016 PloS one Discussion HIV L85A 4 8 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The L85A mutation indirectly resulted in the breakage of the E12 and H89 interaction. 2016 PloS one Discussion HIV L85A 4 8 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The observed effects of the L85A mutation on the E12-H89 interaction were also supported by CLEANEX-PM data (Fig 7D). 2016 PloS one Discussion HIV L85A 28 32 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The possible E12-H89 interaction could also be abolished by H89A. 2016 PloS one Discussion HIV H89A 60 64 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The quick exchanges of the amide protons at S9 (helix 1) and I82 (helix 4) were observed in CLEANEX-PM experiments for L85A. 2016 PloS one Discussion HIV L85A 119 123 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The R2/R1 data revealed that chemical exchange was mainly observed for the residues located in the regions of the alpha1-2 loop and helix 5 for E12A (Fig 4A). 2016 PloS one Discussion HIV E12A 144 148 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. The results of relaxation and amide proton exchange are also consistent with the data from the thermodynamic studies on protein stability using urea denaturation of WT and E12A (Table 1). 2016 PloS one Discussion HIV E12A 172 176 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. These changes, monitored by the chemical shifts of CO (Fig 7C), were probably due to the effects of the structural changes near H33 by the L85A mutation. 2016 PloS one Discussion HIV L85A 139 143 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. This suggested less fluctuation in structures throughout the molecule in E12A than in WT. 2016 PloS one Discussion HIV E12A 73 77 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. This suggested that inhibiting the interaction between E12 and H89 contributed to the building of a few major exchangeable structures around the alpha1-2 loop and helix 5 in the E12A mutant. 2016 PloS one Discussion HIV E12A 178 182 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. This was probably because the E12A mutation had a slight effect on the hydrophobic core. 2016 PloS one Discussion HIV E12A 30 34 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. This was probably due to the indirect effects on the structure near H89 by the L85A mutation. 2016 PloS one Discussion HIV L85A 79 83 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Thus, the relaxation studies on the nano- and pico-second time scale, as well as the amide proton exchange with a milli-second time scale, revealed less fluctuation in the overall structure of E12A than WT. 2016 PloS one Discussion HIV E12A 193 197 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Unexpectedly, the E12A substitution slightly stabilized the structure of p17 on the basis of the experiments of urea denaturation (Table 1). 2016 PloS one Discussion HIV E12A 18 22 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. We tested the further destabilization of E12A by changing the pH to 5.5 (Figs 5 and 6). 2016 PloS one Discussion HIV E12A 41 45 27907055 Effect of Glu12-His89 Interaction on Dynamic Structures in HIV-1 p17 Matrix Protein Elucidated by NMR. Without the interaction between E12 and H89 in E12A, the environment around T53 might be slightly changed. 2016 PloS one Discussion HIV E12A 47 51 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Evidence of a main effect of HIV on brain imaging provides confidence that the absence of a unique contribution of the Tat C31S variant to brain structure was not due to confounds related to the sample or the imaging metrics. 2017 Journal of neurovirology Discussion HIV C31S 123 127 Tat 119 122 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Finally, mice injected with C31C isolates demonstrated more severe memory impairment compared to mice injected with C31S isolates and uninfected controls. 2017 Journal of neurovirology Discussion HIV C31C;C31S 28;116 32;120 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Further, C31C variants isolated from South Africa triggered more monocyte chemotaxis, stimulated CCL2 induction, and damaged neuronal dendritic integrity compared to C31S isolates. 2017 Journal of neurovirology Discussion HIV C31C;C31S 9;166 13;170 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. However, our group recently reported no differences in the cognitive phenotype between individuals with C31C and individuals with C31S, suggesting that the Tat motif is not a primary driver of HIV-related brain dysfunction. 2017 Journal of neurovirology Discussion HIV C31C;C31S 104;130 108;134 Tat 156 159 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Results from the current study demonstrate neuroimaging abnormalities regardless of the Tat C31S motif, indicating that the absence of cognitive variance related to the Tat polymorphism cannot be attributed to the reliance on neuropsychological tests to define brain integrity. 2017 Journal of neurovirology Discussion HIV C31S 92 96 Tat;Tat 88;169 91;172 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. Specifically, while the frequency of C31S was less than 5% in samples from India, the frequency increased to more than 25% in samples from South Africa. 2017 Journal of neurovirology Discussion HIV C31S 37 41 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. The lack of conservation of the C31S variant in South African isolates raises the possibility that previous reports of neuropsychological impairment in HIV-C among South African individuals were driven by the presence of the neurovirulent C31C Tat motif. 2017 Journal of neurovirology Discussion HIV C31C;C31S 239;32 243;36 Tat 244 247 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. The present study clarifies the controversy regarding the impact of the HIV-C Tat C31S substitution on brain integrity. 2017 Journal of neurovirology Discussion HIV C31S 82 86 Tat 78 81 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. The sample size of the C31S genotype group (n = 37) was modest, though sufficient to detect at least a medium effect between groups. 2017 Journal of neurovirology Discussion HIV C31S 23 27 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. These data align with outcomes from previous laboratory studies demonstrating less severe brain injury related to the Tat C31S polymorphism. 2017 Journal of neurovirology Discussion HIV C31S 122 126 Tat 118 121 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. We did not observe a unique signature of brain disruption associated with Tat C31S. 2017 Journal of neurovirology Discussion HIV C31S 78 82 Tat 74 77 27913960 Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity. While most of these investigations did not sequence the dicysteine motif of Tat to confirm the presence of cysteine or serine at position 31, the results are consistent with our previous cognitive study in which C31S status was defined. 2017 Journal of neurovirology Discussion HIV C31S 212 216 Tat 76 79 27928075 Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection. The two most common pncA gene mutations in this study, G145A (D49N PZAse mutation) and A403C (T135P PZAse mutation), were found exclusively in the SIT 42 and SIT 53 isolates, respectively. 2016 The American journal of tropical medicine and hygiene Discussion HIV A403C;D49N;G145A;T135P 87;62;55;94 92;67;60;100 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. Among them, the mutations G190S, K103N, M184V, Y181C, K101E, M41L, and T215F/Y, influencing the HIV resistance to NRTIs and NNRTIs, are observed at a high rate. 2016 BioMed research international Discussion HIV G190S;K101E;K103N;M184V;M41L;T215F;T215Y;Y181C 26;54;33;40;61;71;71;47 31;59;38;45;65;78;78;52 NNRTI;NRTI 124;114 130;119 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. Mutations K103N, M184I, T215Y, G190S, Y181C, K65R, and V108I with prevalences of 0.3 to 7% depending on the region are most frequently detected in the naive HIV-infected individuals. 2016 BioMed research international Discussion HIV G190S;K103N;K65R;M184I;T215Y;V108I;Y181C 31;10;45;17;24;55;38 36;15;49;22;29;60;43 HIV infections 157 169 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. Only two HIV-1 variants carrying solitary G190E and Y181C mutations (causing resistance to RTI) and two HIV-1 specimens with resistance to IIs were found in the examined sample of HIV-1 specimens. 2016 BioMed research international Discussion HIV G190E;Y181C 42;52 47;57 RT 91 94 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The circulating subtype A HIV-1 variants characteristic of Russia are those carrying the V77IPR and/or A62VRT mutations and wild-type (WT) HIV-1. 2016 BioMed research international Discussion HIV A62V;V77I 103;89 109;95 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The mutations A62VRT and V77IPR are certain marker mutations for the subtype A HIV-1 variants circulating in Russia. 2016 BioMed research international Discussion HIV A62V;V77I 14;25 20;31 27957489 HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia. The observed low abundances of A62VRT (8.3%) and V77IPR (11.4%) among the HIV-1 variants in TO may result from importation of WT HIV-1 to this area followed by prevalent development of the "own" focus of HIV-infection epidemic. 2016 BioMed research international Discussion HIV A62V;V77I 31;49 37;55 HIV infections 204 217 27993614 Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes. This difference could be a result of subtype specific polymorphism as L74I was noted in three subtype G samples. 2017 Journal of virological methods Discussion HIV L74I 70 74 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. Importantly, we observed that Vif mutant K26R, in the N-terminus of Vif, while unable to induce A3G degradation by the proteasome was fully able to inhibit A3G translation, demonstrating that these two pathways are independent. 2016 Scientific reports Discussion HIV K26R 41 45 Vif;Vif 30;68 33;71 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. Notably, Vif mutant H42/43N, which unlike mutant K26R, displayed decreased interaction with A3G, was unable to inhibit translation, raising the possibility that Vif/A3G interaction might be required for translational regulation. 2016 Scientific reports Discussion HIV K26R 49 53 Vif;Vif 9;161 12;164 27996044 Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity. The results of our experiments using reporter cells are corroborated by previous studies showing that an HIV-1 mutant bearing mutation K26R in the vif gene replicated in restrictive cells, while a virus with the H42/43N mutations did not. 2016 Scientific reports Discussion HIV K26R 135 139 Vif 147 150 28086929 Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis. M184 V and K103NS were the most prevalent mutations found, reflecting prior treatment with lamivudine, efavirenz or nevirapine. 2017 AIDS research and therapy Discussion HIV K103N;K103S;M184V 11;11;0 17;17;6 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Aside from the increase in potency, a paradoxical increase in cell fusion was observed for W248A at high ligand concentrations. 2016 Pharmacology research & perspectives Discussion HIV W248A 91 96 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Here, we show effective fusion inhibition by small-molecule agonists with no decrease in CCR5 surface expression, in accordance with their lack of beta-arrestin recruitment in L203F CCR5 (Steen et al. 2016 Pharmacology research & perspectives Discussion HIV L203F 176 181 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Of notice, the mutation suffering the biggest fusion impairment, G286F comprising a steric hindrance, is located in TM-7, pointing directly toward TM-6, indicating that the interface between TM-6 and TM-7 toward the main binding pocket (Rosenkilde et al. 2016 Pharmacology research & perspectives Discussion HIV G286F 65 70 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. Since we previously showed that the affinity of Aplaviroc is WT-like on W248A and Y251A (Steen et al. 2016 Pharmacology research & perspectives Discussion HIV W248A;Y251A 72;82 77;87 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. This can also explain why the Y251A and E283A mutations were able to support substantial fusion despite their impairment in gp120 binding (Maeda et al. 2016 Pharmacology research & perspectives Discussion HIV E283A;Y251A 40;30 45;35 gp120 124 129 28097000 Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5. This explanation fits with our observations for the W248A mutation. 2016 Pharmacology research & perspectives Discussion HIV W248A 52 57 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. 6 polymorphic mutations (Q18H, K43E, S68N, Q197K, T215I and E224D) were presented in strains isolated from the deceased patients, while they were completely absent in the strains isolated from the living patients, and they were all positive Darwin selection mutations (Ka/Ks > 1, LOD > 2), but LOD<=2. 2017 PloS one Discussion HIV E224D;K43E;Q18H;Q197K;S68N;T215I 60;31;25;43;37;50 65;35;29;48;41;55 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. 7 (35%) mutations (E6D, E35D, S37N, I93L, E169D, T200V, and T200E) were considered to be potential drug resistance mutations in this study. 2017 PloS one Discussion HIV E169D;E35D;E6D;I93L;S37N;T200E;T200V 42;24;19;36;30;60;49 47;28;22;40;34;65;54 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Among 20 significant death-associated polymorphisms, 13 (65%) polymorphisms (E6D, Q18H, E35D, S37N, T39A, K43E, S68N, I93L, E169D, Q197K, T200V, T200E and E224D) had not been previously reported to be drug resistance mutations, but they were strongly associated with death. 2017 PloS one Discussion HIV E169D;E224D;E35D;E6D;I93L;K43E;Q18H;Q197K;S37N;S68N;T200E;T200V;T39A 124;155;88;77;118;106;82;131;94;112;145;138;100 129;160;92;80;122;110;86;136;98;116;150;143;104 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. For example, T39A and K43E had three (M41L, K43E, and M184V) and seven (D67N, L74V, K101E, L210W, M184V, T215Y, and E224D) target drug resistance mutations, respectively. 2017 PloS one Discussion HIV D67N;E224D;K101E;K43E;K43E;L210W;L74V;M184V;M184V;M41L;T215Y;T39A 72;116;84;22;44;91;78;54;98;38;105;13 76;121;89;26;48;96;82;59;103;42;110;17 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. Some studies had shown that accessory mutations at positions 39 (T39A), 43 (K43E) were more frequent in viral isolates from patients failing therapy than in naive individuals, and those mutations were previously identified as accessory mutations associated with the accumulation of TAMs (thymidine analogue resistance mutations) and with high levels of resistance to nucleoside analogues. 2017 PloS one Discussion HIV K43E;T39A 76;65 80;69 28099515 Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China. The other two non-drug-resistance mutations (E6D and E169D) also had indirect relationship with drug resistance mutations (e.g., E6D:K70R:Q197K; E169D:V179I:G190A), indicating a possible association between these mutations and drug resistance. 2017 PloS one Discussion HIV E169D;E169D;E6D;E6D;G190A;K70R;Q197K;V179I 53;145;45;129;157;133;138;151 58;150;49;132;162;137;143;156 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. For example, Y181C can increase HIV-1 subtype B replicative capacity. 2017 AIDS research and therapy Discussion HIV Y181C 13 18 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. In this study, the most common mutations (M184V/I, K103N, Y181C, etc.) proved HIV-1 fitness to drugs, suggesting that HIV-1 resistant strains would spread out. 2017 AIDS research and therapy Discussion HIV K103N;M184I;M184V;Y181C 51;42;42;58 56;49;49;63 28114955 HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China. Moreover, our study also revealed significant differences in the distributions of M184V/I and M41L mutations among three main genotypes, with M46L/V and T74S only found in CRF01_AE. 2017 AIDS research and therapy Discussion HIV M184I;M184V;M41L;M46L;M46V;T74S 82;82;94;142;142;153 89;89;98;148;148;157 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. Another substitution at this position, V106I (not seen in our study), is significantly more common in subtype-G. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106I 39 44 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. K65R was more common in subtype-C than in A or D, supporting previous observations in subtype-C compared with subtype-AE and subtype-B in a global study of patients failing stavudine-containing regimens, and in comparison with non-C subtypes in an African cohort study (although this effect was not significant after adjustment for drugs). 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R 0 4 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. Q151M, a rare mutation that confers cross-class NRTI resistance, was present in 11% of subtype-C, but negligible levels in other subtypes (not previously described). 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV Q151M 0 5 NRTI 48 52 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. Subtype differences in L210W have previously been noted (higher in A than other subtypes in Nigeria). 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV L210W 23 28 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. The (almost) exclusive occurrence of V106M in subtype-C has been noted previously. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106M 37 42 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. The H221Y mutation (conferring rilpivirine resistance and with Y181C possibly etravirine resistance) has been noted in patients with non-B subtypes failing first-line nevirapine or efavirenz-based regimens in a predominantly subtype-G and CRF02 Nigerian cohort and subtype-C South African cohort. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV H221Y;Y181C 4;63 9;68 28129253 HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. To our knowledge, the differences we found in the other NNRTI DRMs, K101E (rilpivirine and etravirine resistance), Y181C (resistance to all NNRTIs), V108I (efavirenz and nevirapine resistance), and P225H (efavirenz resistance) have not been reported previously. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K101E;P225H;V108I;Y181C 68;198;149;115 73;203;154;120 NNRTI;NNRTI 56;140 61;146 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. Although studies have suggested a low fitness and hence transmission of M184V mutation, studies using more sensitive genotyping assays have shown that this mutation may still be transmitted as minority variants. 2017 PloS one Discussion HIV M184V 72 77 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. As reported from other studies, NNRTI mutations comprised a majority of the detected TDRMs, with K103N/S predominating. 2017 PloS one Discussion HIV K103N;K103S 97;97 104;104 NNRTI 32 37 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. Contrary to other studies in East Africa, we also observed a high frequency of M184V mutation. 2017 PloS one Discussion HIV M184V 79 84 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. M184V is however generally highly revertant. 2017 PloS one Discussion HIV M184V 0 5 28178281 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naive persons in rural western Kenya. The levels of observed NRTI mutations may suggest a change from the predominantly NNRTI to a combined RTI TDR epidemic, with majority of NRTI being M184V mutation. 2017 PloS one Discussion HIV M184V 148 153 NNRTI;NRTI;NRTI;RT 82;23;137;102 87;27;141;105 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Although our analyses were limited to mostly patients enrolled on an EVG-based regimen, other reports have suggested that pre-treatment presence of T97A does not predispose poor treatment outcome or resistance to RAL or DTG as well. 2017 PloS one Discussion HIV T97A 148 152 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Although phenotypic data was available for only the 2 TE patients with emergent T97A+L74M, this combination exhibited the largest reduction in INSTI susceptibility among all T97A-containing isolates, albeit less than 10-fold. 2017 PloS one Discussion HIV L74M;T97A;T97A 85;80;174 89;84;178 INSTI 143 148 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. An analysis of a much larger data set further indicated that the low prevalence of T97A rarely differs by more than 10-fold between subtypes. 2017 PloS one Discussion HIV T97A 83 87 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Because many mutations can act additively or synergistically to reduce drug susceptibility, these results suggest that inter-patient genetic integrase diversity may impact T97A-based INSTI resistance. 2017 PloS one Discussion HIV T97A 172 176 IN;INSTI 141;183 150;188 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. By comparison, emergent T97A alone (i.e., in the absence of primary INSTI RAMs) was inconsistently associated with reduced EVG and/or RAL susceptibility, similar to isolates with pre-existing T97A. 2017 PloS one Discussion HIV T97A;T97A 24;192 28;196 INSTI 68 73 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Detection of T97A in the presence of a primary INSTI RAM (n = 6) was consistent with previous observations of further reduced INSTI susceptibility and increased viral fitness relative to each primary INSTI RAM. 2017 PloS one Discussion HIV T97A 13 17 INSTI;INSTI;INSTI 47;126;200 52;131;205 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Differences in susceptibilities to EVG and/or RAL were noted among T97A-containing isolates relative to their biological cutoffs using the PhenoSense Integrase assay, ranging from low-level to no effect at all. 2017 PloS one Discussion HIV T97A 67 71 IN 151 160 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. During INSTI-based therapy, however, T97A emerged more frequently among TE than TN patients, consistent with previous studies of primary INSTI RAMs. 2017 PloS one Discussion HIV T97A 37 41 INSTI;INSTI 7;137 12;142 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Henceforth, periodic surveillance of T97A integrase mutation patterns and correlation with phenotypic INSTI susceptibility may be necessary to sustain the accuracy of EVG and RAL genotypic algorithms relative to biological or clinical thresholds. 2017 PloS one Discussion HIV T97A 37 41 IN;INSTI 42;102 51;107 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Here, we performed a cross-study pooled analysis of the impact of the T97A integrase mutation (pre-existing and emergent) on INSTI susceptibility and treatment outcome to provide context and guidance on the need for integrase genotyping before INSTI therapy. 2017 PloS one Discussion HIV T97A 70 74 IN;IN;INSTI;INSTI 75;216;125;244 84;225;130;249 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, further investigation is needed to better assess the clinical impact and prevalence of T97A as an escape mutation at specific epitopes relative to corresponding HLA alleles in different patient populations. 2017 PloS one Discussion HIV T97A 96 100 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, little is known about the impact of T97A on subsequent therapy with EVG- or RAL-containing regimens. 2017 PloS one Discussion HIV T97A 45 49 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. However, the selective advantage of emergent T97A during continued INSTI-based therapy remains unclear due to the low number of patients with clinical follow-up data and their varied outcomes. 2017 PloS one Discussion HIV T97A 45 49 INSTI 67 72 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Importantly, in this single occurrence of persistent T97A (no change from pre-treatment sequence), detection at virologic failure was not associated with reduced INSTI susceptibility in vitro. 2017 PloS one Discussion HIV T97A 53 57 INSTI 162 167 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In agreement with previous reports in RAL-treated patients, few patients experienced virologic failure with emergent T97A on EVG or RAL-based therapy (14 of 122; 11%). 2017 PloS one Discussion HIV T97A 117 121 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In agreement with previous studies, the T97A integrase mutation was identified as a naturally occurring low frequency integrase polymorphism among INSTI-naive patients (47 of 3367; 1.4%) and confirmed among a much larger data set of available integrase sequences (255 of 13455; 1.9%). 2017 PloS one Discussion HIV T97A 40 44 IN;IN;IN;INSTI 45;118;243;147 54;127;252;152 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In contrast, a previous study reported a higher frequency of pre-existing T97A among INSTI-naive patients with prior antiretroviral exposure (TE: 4 of 166; 2.4%) than without (TN: 0 of 249; 0%). 2017 PloS one Discussion HIV T97A 74 78 INSTI 85 90 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In contrast, a site-directed T97A mutant virus was previously shown to exhibit low-level reduced EVG susceptibility and no effect on RAL susceptibility. 2017 PloS one Discussion HIV T97A 29 33 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In our analysis, pre-existing T97A was detected less frequently among INSTI-naive patients with prior antiretroviral exposure (TE: 3 of 703; 0.4%) than without (TN: 44 of 2664; 1.7%) and prior antiretroviral exposure was not specifically associated with reduced INSTI susceptibility. 2017 PloS one Discussion HIV T97A 30 34 INSTI;INSTI 70;262 75;267 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In particular, a striking number of patients who developed T97A also had S119 polymorphisms. 2017 PloS one Discussion HIV T97A 59 63 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. In the current study, the T97A+L74M combination was detected in 2 TN patients with pre-existing T97A+L74M and 2 TE patients with emergent T97A+L74M (S1 and S3 Tables). 2017 PloS one Discussion HIV L74M;L74M;L74M;T97A;T97A;T97A 31;101;143;26;96;138 35;105;147;30;100;142 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Indeed, additional secondary INSTI RAMs (e.g., L74M or G163R) may associate with T97A to further reduce susceptibility to EVG and/or RAL in the absence of primary INSTI RAMs, however the selection of these combinations during INSTI-based therapy appears infrequent. 2017 PloS one Discussion HIV G163R;L74M;T97A 55;47;81 60;51;85 INSTI;INSTI;INSTI 29;163;226 34;168;231 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Nevertheless, the fact that most TE and TN patients with pre-existing or emergent T97A retained full or partial susceptibility to EVG and RAL and full susceptibility to DTG should be considered reassuring in contemporary clinical practice. 2017 PloS one Discussion HIV T97A 82 86 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Nonetheless, our data collectively agree with the predictions of ANRS and REGA in that pre-existing T97A with or without phenotypic INSTI resistance does not significantly impact treatment outcome. 2017 PloS one Discussion HIV T97A 100 104 INSTI 132 137 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of interest, the T97A integrase mutation is considered susceptible to INSTIs by ANRS and REGA algorithms, while the level of resistance reported by other algorithms differs: HIVdb (EVG: potential low-level; RAL: low-level) and GeneSeq/GenoSure integrase (EVG: reduced susceptibility/resistant possible; RAL: susceptible). 2017 PloS one Discussion HIV T97A 17 21 IN;IN;INSTI 22;244;70 31;253;76 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Of the INSTI RAMs detected as naturally occurring integrase polymorphisms, only L74M, T97A, E157Q, and G163R are considered secondary INSTI RAMs by at least one algorithm. 2017 PloS one Discussion HIV E157Q;G163R;L74M;T97A 92;103;80;86 97;108;84;90 IN;INSTI;INSTI 50;7;134 59;12;139 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Other integrase mutations and/or secondary INSTI RAM(s) (i.e., M50I, V72N, S119G/P/R, and G163R), identified in INSTI-naive patients with or without pre-existing T97A, also persisted or emerged in patients that developed T97A alone. 2017 PloS one Discussion HIV G163R;M50I;S119G;S119P;S119R;T97A;T97A;V72N 90;63;75;75;75;162;221;69 95;67;84;84;84;166;225;73 IN;INSTI;INSTI 6;43;112 15;48;117 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Our analyses showed that only 1 of 18 patients with pre-existing T97A who enrolled on INSTI-based therapy experienced virologic failure. 2017 PloS one Discussion HIV T97A 65 69 INSTI 86 91 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Our study provides useful information concerning the phenotypic INSTI sensitivity of viral isolates harboring T97A relative to treatment outcome. 2017 PloS one Discussion HIV T97A 110 114 INSTI 64 69 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Overall, T97A did not emerge more frequently in patients harboring non-B subtypes, however, generation of T97A as a single nucleotide transition polymorphism implies that this genetic change can occur easily among most subtypes. 2017 PloS one Discussion HIV T97A;T97A 9;106 13;110 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Similar to earlier reports, we found that T97A pre-existed more frequently among patients harboring non-B than B subtypes. 2017 PloS one Discussion HIV T97A 42 46 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Similarly, our analysis of 3367 integrase sequences derived from TN or TE patients (all INSTI-naive by definition) showed that no primary INSTI RAMs (excluding T97A) and very few secondary INSTI RAMs were present prior to initiation of INSTI-based therapy. 2017 PloS one Discussion HIV T97A 160 164 IN;INSTI;INSTI;INSTI;INSTI 32;88;138;189;236 41;93;143;194;241 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Since T97A can occur before or during INSTI-based treatment, HLA-association of this integrase polymorphism may impart a selective advantage to evade cellular immune response which could impact frequency of transmitted INSTI resistance. 2017 PloS one Discussion HIV T97A 6 10 IN;INSTI;INSTI 85;38;219 94;43;224 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Since T97A has been associated with INSTI resistance in patients experiencing virologic failure on EVG or RAL, we sought to address the concern of whether this naturally occurring integrase polymorphism could change the current paradigm for supplemental integrase genotyping prior to INSTI-based therapy. 2017 PloS one Discussion HIV T97A 6 10 IN;IN;INSTI;INSTI 180;254;36;284 189;263;41;289 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. The T97A integrase mutation, considered a secondary INSTI RAM in most publications, has been identified periodically in patients experiencing virologic failure on INSTI-based therapy and is also an infrequent integrase polymorphism associated with low-level reduced susceptibility to EVG and/or RAL. 2017 PloS one Discussion HIV T97A 4 8 IN;IN;INSTI;INSTI 9;209;52;163 18;218;57;168 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Therefore, pre-existence of T97A, with or without additional integrase mutations, poses a minimal risk of compromised virologic response for INSTI-naive patients enrolling on INSTI-based therapy. 2017 PloS one Discussion HIV T97A 28 32 IN;INSTI;INSTI 61;141;175 70;146;180 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. These findings suggest that pre-existence of T97A, with or without partially reduced INSTI susceptibility, does not significantly impact treatment outcome or impart a strong selective advantage under INSTI pressure to drive virus escape and/or the evolution of INSTI resistance. 2017 PloS one Discussion HIV T97A 45 49 INSTI;INSTI;INSTI 85;200;261 90;205;266 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. These results are also consistent with previously studied integrase polymorphisms, including some minor/secondary INSTI RAMs (e.g., S119P and G163R), but discordant from major/primary INSTI RAMs. 2017 PloS one Discussion HIV G163R;S119P 142;132 147;137 IN;INSTI;INSTI 58;114;184 67;119;189 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. This is important as it suggests that maintenance of reasonable systemic exposures of pharmacoenhancer-boosted EVG (85/125/150 mg once a day) or RAL (400 mg twice a day) as part of a complete antiretroviral regimen are sufficient to inhibit the T97A integrase mutation. 2017 PloS one Discussion HIV T97A 245 249 IN 250 259 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Thus, further study is needed to resolve the phenotypic significance of integrase polymorphism(s) that may associate with T97A. 2017 PloS one Discussion HIV T97A 122 126 IN 72 81 28212411 Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome. Thus, the clinical significance of T97A frequencies among INSTI-naive patients could be attributable to multiple factors, including, but not limited to enrollment bias over time or differences among prior antiretroviral regimens. 2017 PloS one Discussion HIV T97A 35 39 INSTI 58 63 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. A recent study showed that low-level of CSF HIV-1 RNA was associated with better neurocognitive outcomes, and hypothesized that one mechanism was through DRMs such as M184V, which reduce viral fitness but may stimulate a more effective immune response. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 167 172 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. Although there has been a declining trend in resistance mutations among HIV+ individuals in resource-rich settings, a 2015 study in ART-experienced patients with plasma HIV-1RNA >50 copies per milliliter showed that 12.5% and 19.8% of individuals had unique CSF resistance mutations to RT and protease, respectively; M41L and T215Y, were statistically more prevalent in the CSF. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M41L;T215Y 317;326 321;331 PR;RT 293;286 301;288 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. However, the combination of poor CSF penetration by tenofovir, a widely used NRTI in ART and M184V/I mutation leading to emtricitabine or lamuvidine resistance may lower the threshold for subsequent CSF mutations that could lead to NRTI cross resistance. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 93;93 100;100 NRTI;NRTI 77;232 81;236 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. In our study, M184V/I, T215Y, D67N, and M41L were the most commonly detected CSF mutations. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV D67N;M184I;M184V;M41L;T215Y 30;14;14;40;23 34;21;21;44;28 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. M184V/I were the most frequently observed mutations in all cases present in 74% of CSF isolates from individuals with plasma levels <=50 copies per milliliter, and frequently occurring in the presence of other DRMs. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 0;0 7;7 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. Our estimates suggest that individuals with a recent history of LLV or historical virologic failure with M184V/I mutations are potentially at elevated risk for CSF escape. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 105;105 112;112 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. The high frequency of M184V/I mutations reported here and in the literature, and simultaneous presence of TAMs in neurologically symptomatic CSF escape raises the possibility that the M184V/I mutations could be a factor influencing CNS viral reservoirs and CSF escape. 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184I;M184V;M184V 184;22;22;184 191;29;29;191 28328546 Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults. Three CSF integrase mutations were identified in CSF (N155H, Y143C, and Q148R). 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV N155H;Q148R;Y143C 54;72;61 59;77;66 IN 10 19 28328548 Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT. In two cases, resistance mutations were detected by NGS only; in the third case, one mutation was detected by routine HIV genotyping (M184I) and one was detected by NGS only (K65R). 2017 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K65R;M184I 175;134 179;139 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. However, the overall rate of first-line regimen failure in Aruba is similar to settings in developed countries where no such increase in transmission of K103N-variants has been reported. 2017 Clinical infectious diseases Discussion HIV K103N 153 158 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. However, we have previously shown that K103N has limited impact on viral fitness in vitro and long-term persistence of this mutation has also been observed in vivo. 2017 Clinical infectious diseases Discussion HIV K103N 39 44 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. In 2015, NNRTI resistance mutation K103N was found in nearly half of the newly diagnosed individuals in Aruba who were tested for resistance before initiation of cART. 2017 Clinical infectious diseases Discussion HIV K103N 35 40 NNRTI 9 14 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. In this cohort we observed persistence of mutation K103N at high frequencies despite the long duration of infection in some patients. 2017 Clinical infectious diseases Discussion HIV K103N 51 56 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Phylogenetic analysis revealed that strains with K103N were introduced into the therapy-naive population multiple times, in the MSM as well as the heterosexual population. 2017 Clinical infectious diseases Discussion HIV K103N 49 54 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. Regarding the consequences for clinical care, in our survey the results of resistance testing were reported to the clinicians, who often initiated an adjusted regimen if K103N was detected. 2017 Clinical infectious diseases Discussion HIV K103N 170 175 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. The increased transmission of K103N-variants could be a result of a high degree of therapy failure in individuals on efavirenz or nevirapine-based regimens. 2017 Clinical infectious diseases Discussion HIV K103N 30 35 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. The long-term persistence of variants with K103N after transmission underlines their threatening potential to spread widely among therapy-naive individuals. 2017 Clinical infectious diseases Discussion HIV K103N 43 48 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. We did not find evidence of reverted minority K103N variants with next generation sequencing in patients diagnosed with wild-type virus based on population sequencing. 2017 Clinical infectious diseases Discussion HIV K103N 46 51 28329390 High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients. We showed that transmission of K103N-variants in Aruba was frequently linked to individuals who were originating from and/or diagnosed with HIV in surrounding countries. 2017 Clinical infectious diseases Discussion HIV K103N 31 36 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Although K65R, Q151M and M184V might be selected under NRTI pressure in HIV-1 as well as in HIV-2, the classwide-resistant triple mutant is characteristic of the HIV-2 RT since Q151M is the preferred mutation selected during treatment with AZT. 2017 Scientific reports Discussion HIV K65R;M184V;Q151M;Q151M 9;25;15;177 13;30;20;182 NRTI;RT 55;168 59;170 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Although several studies carried out with HIV-1 RT variants have shown that K65R and other mutations conferring resistance to nucleoside analogues (e.g. 2017 Scientific reports Discussion HIV K65R 76 80 RT 48 50 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. As in HIV-1BH10 RT, mutant HIV-1 group O RT bearing the K65R change showed reduced kpol, although in this case the enzyme had increased affinity for the incoming dNTP. 2017 Scientific reports Discussion HIV K65R 56 60 RT;RT 16;41 18;43 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Classwide NRTI resistance in HIV-2 is conferred by mutations K65R, Q151M and M184V. 2017 Scientific reports Discussion HIV K65R;M184V;Q151M 61;77;67 65;82;72 NRTI 10 14 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Furthermore, estimates of HIV-1 mutant frequencies obtained in cell culture after one round of replication were consistent with the enzymatic data and showed a 3.3-fold reduction for virus containing the K65R mutation in their RT. 2017 Scientific reports Discussion HIV K65R 204 208 RT 227 229 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Furthermore, studies with the group O enzyme also showed the increased nucleotide selectivity of the double-mutant K65R/V75I in comparison with the RT bearing the single amino acid substitution V75I. 2017 Scientific reports Discussion HIV K65R;V75I;V75I 115;120;194 119;124;198 RT 148 150 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In contrast, our results show that K65R in HIV-2ROD RT had almost no effect on the overall fidelity of the enzyme, although it produced a modest decrease of its base substitution error rate. 2017 Scientific reports Discussion HIV K65R 35 39 RT 52 54 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In contrast, the substitution of Met for Gln151 (Q151M) enhanced the catalytic efficiency of the HIV-1 RT due to an increased kpol, an effect that we also observed with this amino acid substitution in the HIV-2 RT. 2017 Scientific reports Discussion HIV Q151M;Q151M 49;33 54;47 RT;RT 103;211 105;213 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In general, the results of our misinsertion and mispair extension fidelity assays using the 31/21-mer template-primer did not reveal significant differences between HIV-2 RTs bearing mutation K65R and the WT enzyme, except for the extension of G:G mispairs which was less efficient in the case of the mutant enzyme. 2017 Scientific reports Discussion HIV K65R 192 196 RT 171 174 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In studies carried out with HIV-1 group O RT, K65R was found to have a large impact on nucleotide selectivity. 2017 Scientific reports Discussion HIV K65R 46 50 RT 42 44 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. In support of this notion, crystal structures of ternary complexes composed of mutant K65R HIV-1BH10 RT, double-stranded DNA and incoming nucleotides. 2017 Scientific reports Discussion HIV K65R 86 90 RT 101 103 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Interestingly, WT and mutant SIVmac239 showed similar mutation rates in cell-based assays although K65R-containing viruses showed slightly reduced variability. 2017 Scientific reports Discussion HIV K65R 99 103 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Introduction of K65R in the sequence of HIV-1ESP49 RT decreased misinsertion and mispair extension ratios for all tested nucleotides and mismatched template-primers. 2017 Scientific reports Discussion HIV K65R 16 20 RT 51 53 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. K103R) was found to be less infectious than the WT. 2017 Scientific reports Discussion HIV K103R 0 5 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. M184V alone decreases the catalytic efficiency by reducing the nucleotide binding affinity of the RT. 2017 Scientific reports Discussion HIV M184V 0 5 RT 98 100 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. M184V) increase their DNA polymerase fidelity, there are examples of NRTI resistance mutations having little effect on the accuracy of HIV-1 RT (e.g. 2017 Scientific reports Discussion HIV M184V 0 5 Pol;NRTI;RT 26;69;141 36;73;143 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. On the other hand, the results with K65R were slightly different in the HIV-1BH10 RT as compared with the HIV-2ROD enzyme. 2017 Scientific reports Discussion HIV K65R 36 40 RT 82 84 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. Our analysis on the effects of K65R, Q151M and M184V on nucleotide incorporation kinetics revealed that M184V was responsible for the reduced catalytic efficiency of classwide-resistant HIV-2 RT. 2017 Scientific reports Discussion HIV K65R;M184V;M184V;Q151M 31;47;104;37 35;52;109;42 RT 192 194 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. showed that K65R reduced the catalytic efficiency of HIV-1BH10 RT by decreasing its nucleotide incorporation rates (kpol) for different dNTPs, while in our assays with HIV-2 RT, the substitution had almost no effect on the catalytic parameters of the enzyme. 2017 Scientific reports Discussion HIV K65R 12 16 RT;RT 63;174 65;176 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The effects of K65R on the evolutionary rate of HIV-2 have not been assessed. 2017 Scientific reports Discussion HIV K65R 15 19 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The increased intrinsic fidelity conferred by K65R appears to be a specific characteristic of HIV-1 RT and not shared by RTs of the HIV-2/SIV lineage. 2017 Scientific reports Discussion HIV K65R 46 50 RT;RT 100;121 102;124 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. The results of those studies were consistent with the kinetic data reported here and showed that M184V produced a significant reduction of the catalytic efficiency of the HIV-1 polymerase due to a decreased dNTP binding affinity. 2017 Scientific reports Discussion HIV M184V 97 102 Pol 177 187 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. There were relatively small differences in fidelity between the classwide NRTI-resistant K65R/Q151M/M184V RT and the WT HIV-2ROD enzyme, despite the presence of K65R in the mutational complex. 2017 Scientific reports Discussion HIV K65R;M184V;Q151M;K65R 89;100;94;161 93;105;99;165 NRTI;RT 74;106 78;108 28333133 Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases. These effects were unexpected considering that K65R alone produced large increases in fidelity in forward mutation assays carried out with HIV-1 RTs from phylogenetically distant strains such as HXB2 (group M subtype B) or ESP49 (group O). 2017 Scientific reports Discussion HIV K65R 47 51 RT 145 148 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Additionally, the clinical significance of several mutations that occurred commonly in combination with K65R including A62V, S68G/N/D, L74I, V75L and Y115F requires further phenotypic and clinical studies to better understand their effects on both TDF and the newly developed prodrug tenofovir alafenamide (TAF). 2017 EBioMedicine Discussion HIV A62V;K65R;L74I;S68D;S68G;S68N;V75L;Y115F 119;104;135;125;125;125;141;150 123;108;139;133;133;133;145;155 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Because most of the additional TDF-selected TRAMs usually occurred in combination with K65R, the overall prevalence of one or more of the 12 TDF-selected TRAMs in this study was only slightly higher than the overall prevalence of K65R/N and/or K70E/G/Q in individuals with VF on a TDF-containing first-line WHO recommended regimen (54% vs. 2017 EBioMedicine Discussion HIV K65N;K65R;K65R;K70E;K70G;K70Q 230;87;230;244;244;244 236;91;236;252;252;252 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. However, previously published data outlined below suggest that these additional mutations may confer greater reductions in TDF susceptibility than K65R alone. 2017 EBioMedicine Discussion HIV K65R 147 151 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. In conclusion, this study shows that the spectrum of TDF-selected mutations extends beyond K65R/N and K70E/G/Q. 2017 EBioMedicine Discussion HIV K65N;K65R;K70E;K70G;K70Q 91;91;102;102;102 97;97;110;110;110 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. In these individuals, M184V eventually replaces M184I because its replication capacity is less attenuated than that of M184I. 2017 EBioMedicine Discussion HIV M184I;M184I;M184V 48;119;22 53;124;27 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. In these trials, few individuals with VF developed RT mutations other than NNRTI-resistance mutations and the cytosine analog resistance mutations M184V/I. 2017 EBioMedicine Discussion HIV M184I;M184V 147;147 154;154 NNRTI;RT 75;51 80;53 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. K65R was the most commonly occurring TDF-selected mutation, however, it rarely emerged in individuals undergoing frequent virological monitoring in whom therapy was changed when VF was first detected. 2017 EBioMedicine Discussion HIV K65R 0 4 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. K70E has been reported to rarely occur in combination with K65R because of the reduced replication fitness when both mutations occur in the same virus. 2017 EBioMedicine Discussion HIV K65R;K70E 59;0 63;4 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. K70E/G/Q/N/T have previously been reported to occur rarely in individuals receiving d4T, ABC, and TDF-containing regimens and to be associated with slightly reduced susceptibility to these NRTIs. 2017 EBioMedicine Discussion HIV K70E;K70G;K70N;K70Q;K70T 0;0;0;0;0 12;12;12;12;12 NRTI 189 194 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. L74I, which is also primarily an ABC-resistance mutation, has been reported to be selected by TDF. 2017 EBioMedicine Discussion HIV L74I 0 4 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. M184I has been reported to often precede the development of M184V among individuals receiving a cytosine analog. 2017 EBioMedicine Discussion HIV M184V;M184I 60;0 65;5 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Of the 12 TDF-selected TRAMs, the SDRM list includes the established TDF-resistance mutations K65R and K70E, and the established ABC-resistance mutations L74I and Y115F. 2017 EBioMedicine Discussion HIV K65R;K70E;L74I;Y115F 94;103;154;163 98;107;158;168 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Of the cytosine analog resistance mutations, M184V occurred more commonly in the thymidine analog group whereas M184I occurred more commonly in the TDF group. 2017 EBioMedicine Discussion HIV M184I;M184V 112;45 117;50 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Of these, K70G occurred in just four individuals (Supplementary Table 2). 2017 EBioMedicine Discussion HIV K70G 10 14 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. S68N has been selected in vitro by TDF and shown to further reduce TDF susceptibility when present with K65R. 2017 EBioMedicine Discussion HIV K65R;S68N 104;0 108;4 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Several of the 12 TDF-selected TRAMs have been previously associated with K65R, TDF selection pressure, or reduced in vitro TDF susceptibility. 2017 EBioMedicine Discussion HIV K65R 74 78 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Specifically, A62V and S68G have been reported to improve the replication of viruses with K65R. 2017 EBioMedicine Discussion HIV A62V;K65R;S68G 14;90;23 18;94;27 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The 12 TDF-selected TRAMs included A62V, K65R/N, S68G/D/N, K70E/Q/T, L74I, V75L, and Y115F. 2017 EBioMedicine Discussion HIV A62V;K65N;K65R;K70E;K70Q;K70T;L74I;S68D;S68G;S68N;V75L;Y115F 35;41;41;59;59;59;69;49;49;49;75;85 39;47;47;67;67;67;73;57;57;57;79;90 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The established TDF-resistance mutations K65R and K70E have been shown to attenuate virus replication in vitro and in animal models. 2017 EBioMedicine Discussion HIV K65R;K70E 41;50 45;54 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The most commonly occurring of these were K65R (39.5%; 1134/2873), S68G/N (21.4%; 614/2873), Y115F (11.9%; 343/2873), K70E/Q/T (10.9%; 312/2873), A62V (10.4%; 298/2873), and L74I (6.4%; 165/2873). 2017 EBioMedicine Discussion HIV A62V;K65R;K70E;K70Q;K70T;L74I;S68G;S68N;Y115F 146;42;118;118;118;174;67;67;93 150;46;126;126;126;178;73;73;98 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The remaining six TDF-selected TRAMs, K65N, S68N/D, K70Q/T, and V75L are nonpolymorphic and should be considered for possible addition to the SDRM list. 2017 EBioMedicine Discussion HIV K65N;K70Q;K70T;S68D;S68N;V75L 38;52;52;44;44;64 42;58;58;50;50;68 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. The same antagonistic interaction was not observed between K65R and K70T/N. 2017 EBioMedicine Discussion HIV K65R;K70N;K70T 59;68;68 63;74;74 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Two of these TRAMs are polymorphic and are therefore not SDRM candidates for monitoring transmitted drug-resistance: S68G occurs in 1.6% to 6.6% of ARV-naive individuals depending on subtype and A62V is the consensus residue in subtype A viruses in the Former Soviet Union countries. 2017 EBioMedicine Discussion HIV A62V;S68G 195;117 199;121 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. We confirmed this observation and demonstrated that the same antagonistic interaction exists between K65R and K70Q. 2017 EBioMedicine Discussion HIV K65R;K70Q 101;110 105;114 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. We speculate that M184I occurred more commonly in the TDF group compared with the thymidine analog group because the duration of therapy was shorter in the TDF group - possibly because of more frequent virological monitoring in this somewhat more recent cohort. 2017 EBioMedicine Discussion HIV M184I 18 23 28365230 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. Y115F, although it is primarily an abacavir (ABC)-resistance mutation, has been selected in vitro by TDF and shown to reduce TDF susceptibility. 2017 EBioMedicine Discussion HIV Y115F 0 5 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. 1), this suggests that the negative effect of R263K on HIV fitness is exclusively linked to the integration process. 2017 mBio Discussion HIV R263K 46 51 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Adding to the difficulty of monitoring such cases, we recently reported a transient R263K substitution in the proviral DNA of a chronically infected individual 4 weeks after initiation of DTG-based ART. 2017 mBio Discussion HIV R263K 84 89 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Additional clinical studies are also needed to study the clinical impact of the R263K substitution on both viral load and viral reservoirs. 2017 mBio Discussion HIV R263K 80 85 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Alternatively, R263K viruses may be so poorly fit that they may be outcompeted by WT strains upon virological failure. 2017 mBio Discussion HIV R263K 15 20 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. An eventual de novo virological failure with resistance mutations may derive from preexisting rare polymorphisms, including E157Q and others. 2017 mBio Discussion HIV E157Q 124 129 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Changes in integration sites were observed when infections are performed in the presence of suboptimal concentrations of RAL or noncatalytic integrase inhibitors but also with the D116N catalytically inactive integrase mutant. 2017 mBio Discussion HIV D116N 180 185 IN;IN 141;209 150;218 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Importantly, our results show no differences in the amounts of both early (minus-strand DNA transfer) and late reverse transcripts that were produced during infections with WT or R263K viruses. 2017 mBio Discussion HIV R263K 179 184 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In addition to decreasing integration levels, the R263K substitution may also alter integration sites. 2017 mBio Discussion HIV R263K 50 55 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In the absence of longitudinal measures of cell-associated HIV DNA levels in individuals whose viruses have developed an R263K substitution under DTG-based therapy, the clinical relevance of our results is unknown. 2017 mBio Discussion HIV R263K 121 126 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In the case of the R263K substitution, however, these changes are unlikely to alter the establishment of or reactivation from latency, since we previously reported these processes to be unaffected by this substitution. 2017 mBio Discussion HIV R263K 19 24 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. In treatment-experienced individuals who experienced treatment failure while using DTG, the R263K substitution in integrase is the most common mutation reported thus far. 2017 mBio Discussion HIV R263K 92 97 IN 114 123 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Indeed, progressive decreases in the levels of integrated DNA with the R263K mutant as shown in. 2017 mBio Discussion HIV R263K 71 76 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. One explanation is that R263K confers levels of resistance against DTG that are insufficient for treatment failure. 2017 mBio Discussion HIV R263K 24 29 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Sequencing of R263K integration sites is under way. 2017 mBio Discussion HIV R263K 14 19 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The present study further shows that prolonged infections with R263K-containing viruses result in a progressive decline in integrated HIV-1 DNA over time. 2017 mBio Discussion HIV R263K 63 68 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. The R263K substitution commonly results from a single nucleotide change, in most cases a single G A transition. 2017 mBio Discussion HIV R263K 4 9 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. This effect was specific, as infections with the K65R mutant did not result in diminished HIV-1 integration over time. 2017 mBio Discussion HIV K65R 49 53 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. This observation was even more pronounced with the H51Y/R263K combination of substitutions. 2017 mBio Discussion HIV H51Y;R263K 51;56 55;61 28377526 The R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration. Together with the fact that R263K did not decrease reverse transcription. 2017 mBio Discussion HIV R263K 28 33 RT 51 72 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. A further consideration is the fact that the K65R mutation could have disappeared due to the adverse effect it has on replication fitness of the virus upon stopping combination ART and could therefore be underrepresented in our database. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 45 49 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. A recent multicentre retrospective cohort study (TenoRes) that combined data from cohorts and clinical trials across 36 countries found K65R prevalence rates of more than 50% in sub-Saharan African patients with treatment failure on tenofovir- and NNRTI-based regimens. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 136 140 NNRTI 248 253 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. An explanation for the differences in treatment response and risk of K65R developing between subtypes could be that a single point mutation under an optimal treatment setting does not affect outcome. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 69 73 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Data analysis from the UK CHIC Study, which is a representative cohort of the UK HIV population on ART, shows the prevalence of K65R to be 13.2% in those failing a tenofovir- and efavirenz-based regimen. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 128 132 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Furthermore, a separate sensitivity analysis (Table 4) that additionally controlled for ethnicity and exposure group confirmed the association between subtype C and K65R. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 165 169 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. However, the high prevalence of K65R in low-income countries where K65R presence can be as high as 50% has led to increasing use of zidovudine in second-line therapy. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R;K65R 32;67 36;71 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. However, this would not have unduly influenced the results as this study mainly explored the hypothesis that the subtype C template has a predilection for developing a K65R mutation. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 168 172 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. However, when other factors that lead to differential non-adherence, such as demographics and clinical characteristics, are present then subtype C viruses have a greater propensity to develop a K65R mutation. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 194 198 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. In conclusion, our analysis shows that patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 112 116 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. It is also possible that K65R existed as a minority variant prior to therapy as a result of undetected transmitted drug resistance, but the possibility of this is small and should not have affected our results. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 25 29 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. It is difficult to determine the exact influence subtype has on the propensity of K65R development in patients with virological failure due to the fact that subtype C is linked to certain demographic factors such as ethnicity, immigration, culture, lifestyle and socioeconomic status. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 82 86 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. It still has to be established if minority variant K65R substantially increases a patient's risk of virological failure in a resource-limited setting. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 51 55 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. K65R resistance also tends to disappear within a month of stopping ART and therefore more sensitive baseline resistance testing may need to be performed in patients with a history of PrEP usage without adequate monitoring. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 0 4 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Looking at other factors associated with the emergence of K65R, as reported by von Wyl et al., we also found that current zidovudine or boosted PI-containing therapy conferred protection (adjusted OR = 0.41 and 0.29, respectively). 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 58 62 PI 144 146 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Of interest, we also observed that K65R was common amongst patients who had never been prescribed tenofovir (Figure 2). 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 35 39 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Our analysis provides strong clinical evidence that there is an increased risk of finding the K65R mutation among subtype C viruses following virological failure. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 94 98 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Our data are consistent with previous evidence that subtype C is a strong risk factor for the development of K65R in patients with virological failure. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 109 113 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Our data would suggest a possible increased risk of acquiring K65R in patients with subtype C virus who fail PrEP, especially in settings where PrEP is not stopped soon after seroconversion. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 62 66 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Our results are in keeping with previous reports and confirm that patients with subtype C are twice as likely as those with other subtypes to develop a K65R mutation. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 152 156 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Small retrospective retreatment cohort studies suggested that second-line therapy is as successful with K65R as when the mutation is not present, usually with zidovudine in the regimen. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 104 108 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. So far, PrEP studies using tenofovir +- emtricitabine have reported a low incidence of K65R acquisition when failing tenofovir-based PrEP, even when more sensitive sequencing is employed. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 87 91 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The clinical implication may therefore be that patients who are infected with subtype C viruses are at an increased risk of virological failure because of the propensity of the virus to develop a K65R mutation when on a tenofovir-based regimen. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 196 200 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The influence of subtype C on the likelihood of K65R development has not yet been studied in patients with PrEP failure due to the low incidence of breakthrough infections and resistance in clinical trial settings. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 48 52 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The OR of 1.95 we observed is roughly in keeping with the ORs observed in the TenoRes cohort study (OR = 2.44) and the EuResist consortium study (OR = 2.22), which confirms that subtype C is significantly associated with a higher probability of K65R emergence. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 245 249 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The risk of K65R developing was increased on NNRTI-based therapy (adjusted OR = 1.78) and the highest risk was observed with current treatment with tenofovir (adjusted OR = 5.03). 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 12 16 NNRTI 45 50 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. The wide variation in the worldwide prevalence of K65R is most likely explained by different standards of care, most notably the length of time spent on failing ART, but our data indicate that subtype C per se contributes to the high prevalence seen in countries where subtype C is prevalent. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 50 54 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. There is a further increase in K65R prevalence in developing countries in patients who fail a non-zidovudine-containing NRTI regimen. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 31 35 NRTI 120 124 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. There is generally a low overall prevalence of K65R reported in various resistance databases. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 47 51 28379449 An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs. Various other factors have also been shown to increase the risk of K65R development such as current tenofovir and/or NNRTIs, dual didanosine + tenofovir therapy, low starting CD4 count and length of virological failure. 2017 The Journal of antimicrobial chemotherapy Discussion HIV K65R 67 71 NNRTI 117 123 28382208 Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial. The most frequently emerging etravirine RAMs, Y181C, E138A, and M230L (>=5 VFs) have also been observed previously in patients with VF in etravirine trials, as has the only other NNRTI RAM that emerged in >=5 VFs, H221Y. 2017 SAGE open medicine Discussion HIV E138A;H221Y;M230L;Y181C 53;214;64;46 58;219;69;51 NNRTI 179 184 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. L74 mutations alone cause intermediate-level resistance to ABC but when combined with the common mutation M184V as was the case for every child with identified L74V/I in our study, this causes high-level resistance to ABC and likely necessitates a change in the ART regimen to regain virologic suppression. 2017 The Pediatric infectious disease journal Discussion HIV L74I;L74V;M184V 160;160;106 166;166;111 28383390 High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy. We found that almost all children on ART with VF and L74V/I mutations were on ABC-containing regimens. 2017 The Pediatric infectious disease journal Discussion HIV L74I;L74V 53;53 59;59 28383402 Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice. The suggestion of more M184 V mutations in the MTR group is however intriguing and deserves further study. 2017 Medicine Discussion HIV M184V 23 29 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Dolutegravir is a drug for which thein vitro acquisition of singlet substitutions, including R263K, S153Y and H51Y, interfered with further acquisition of secondary resistance mutations. 2017 The Journal of antimicrobial chemotherapy Discussion HIV H51Y;R263K;S153Y 110;93;100 114;98;105 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Findings reported herein revealed the emergence of viral variants coexpressing R263K/M184V and R263K/T66I as dominant (>98%) quasi-species under selective pressure with dolutegravir + lamivudine and elvitegravir, respectively. 2017 The Journal of antimicrobial chemotherapy Discussion HIV M184V;R263K;R263K;T66I 85;79;95;101 90;84;100;105 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Furthermore, viruses obtained by site-directed mutagenesis of the laboratory strain pNL4.3 with R263K or H51Y are severely compromised in their ability to acquire or coexist with other mutations, such as M184V and T66I. 2017 The Journal of antimicrobial chemotherapy Discussion HIV H51Y;M184V;R263K;T66I 105;204;96;214 109;209;101;218 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Notably, cluster 50 (cluster size 140) and cluster 99-K103N (cluster size 34) remain persistent sub-epidemics harbouring G190A and K103N, respectively. 2017 The Journal of antimicrobial chemotherapy Discussion HIV G190A;K103N;K103N 121;131;54 126;136;59 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Our findings show that R263K and S153Y, once acquired, may not revert. 2017 The Journal of antimicrobial chemotherapy Discussion HIV R263K;S153Y 23;33 28;38 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Our previous studies also showed the development of G118R (GGA AGA) in two patients failing dolutegravir monotherapy. 2017 The Journal of antimicrobial chemotherapy Discussion HIV G118R 52 57 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Resistance to dolutegravir has, however, been limited to the G118R case and a novel resistance pathway from a raltegravir-experienced patient harbouring the N155H mutation. 2017 The Journal of antimicrobial chemotherapy Discussion HIV G118R;N155H 61;157 66;162 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. Studies are ongoing to ascertain RT and integrase activity for WT and resistant (R263K or S153Y) cluster 185 isolates, compared with pNL4.3. 2017 The Journal of antimicrobial chemotherapy Discussion HIV R263K;S153Y 81;90 87;95 IN;RT 40;33 49;35 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The acquisition of E157Q (94% and 99%) by two viruses (and) coexpressing T66I/R263K (>98%, isolate 14947) or a mixed T66I (85.9%) and H51Y (15.9%) quasi-species (isolate 14997) under elvitegravir pressure suggests that E157Q may serve as an accessory mutation that restores viral replicative fitness and increases resistance. 2017 The Journal of antimicrobial chemotherapy Discussion HIV E157Q;E157Q;H51Y;R263K;T66I;T66I 19;219;134;78;73;117 24;224;138;83;77;121 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The combination of R263K with viruses containing M184I or M184V mutations in dolutegravir + lamivudine selections further reduced viral replication competence compared with when only single mutations were present. 2017 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V;R263K 49;58;19 54;63;24 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The emergence of select mutations under dolutegravir pressure, including R263K (AGA AAA or AGG AAG), G163R (GGA AGA or GGG AGG) and E138K (GAA AAA, GAG AAG), may be related to APOBEC-mediated G A hypermutation. 2017 The Journal of antimicrobial chemotherapy Discussion HIV E138K;G163R;R263K 132;101;73 137;106;78 Gag 148 151 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The generation of M184I (ATG ATA) can also arise from G to A hypermutation although M184V leads to higher fold drug resistance. 2017 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 18;84 23;89 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The high potency for dolutegravir resulted in EC50s of 1 nM (0.4 ng/ml) and drug concentrations could not be increased beyond 5 to 10 nM with R263K or S153Y to sustainin vitro viral replication in CBMCs. 2017 The Journal of antimicrobial chemotherapy Discussion HIV R263K;S153Y 142;151 147;156 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. The rapid acquisition of R263K, S153Y or H51Y with dolutegravir was unexpected given the isolated number of reported cases of resistance in the clinic. 2017 The Journal of antimicrobial chemotherapy Discussion HIV H51Y;R263K;S153Y 41;25;32 45;30;37 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. These patients harboured a rare GGA natural polymorphism (1.5% prevalence) compared with the majority of clinical viral isolates harbouring GGC (79%) or GGT (18%) glycine motifs where G118R acquisition would require two point mutations (GGG AGA or GGU AGA) or single unfavourable transversions (GGG CGG orGGU CGT), respectively. 2017 The Journal of antimicrobial chemotherapy Discussion HIV G118R 184 189 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. This contrasts with elvitegravir selections, such as the cluster 185 isolate, 14947, where acquisition of T66I preceded R263K, resulting in higher levels of resistance, the acquisition of the compensatory E157Q and viral escape. 2017 The Journal of antimicrobial chemotherapy Discussion HIV E157Q;R263K;T66I 205;120;106 210;125;110 28472323 HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters. We observed that the rate of appearance of R263K with dolutegravir was as rapid as that observed for the appearance of M184V with lamivudine. 2017 The Journal of antimicrobial chemotherapy Discussion HIV M184V;R263K 119;43 124;48 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. As predicted in the electrophoretic mobility shift assay (EMSA) experiment, the interaction between TatD60 (with Ser46Phe) and TAR were different in the simulation experiment. 2017 Frontiers in microbiology Discussion HIV S46F 113 121 Tat 100 103 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Both in silico and in vitro studies show that the Ser46Phe mutation in Tat results in enhanced transactivation. 2017 Frontiers in microbiology Discussion HIV S46F 50 58 Tat 71 74 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Correlating Tat variants, especially variants with Ser46Phe, with the course of the disease, as well as response to ART, would provide molecular and clinical insights to managing HIV-1 patients in North India. 2017 Frontiers in microbiology Discussion HIV S46F 51 59 Tat 12 15 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. From 15 variants, we selected three variants namely TatN12 (Leu35Pro; Gly44Ser), TatD60 (Ser46Phe), and TatVT6 (B/C recombinant) as representative variants to understand the role of genetic determinants on transactivation, TAR interaction and stability. 2017 Frontiers in microbiology Discussion HIV G44S;L35P;S46F 70;60;89 78;68;97 Tat;Tat 52;81 55;84 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Most of these residues were highly conserved among North Indians; however, we found that variants with Ser46Phe showed higher transactivation of LTR than TatC indicating the importance of this mutation. 2017 Frontiers in microbiology Discussion HIV S46F 103 111 LTR 145 148 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Next, to demonstrate how Ser46Phe contributed toward high transactivation activity. 2017 Frontiers in microbiology Discussion HIV S46F 25 33 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. There could be other factors involved in the decline of CD4 counts in HIV-1 infected patients, however, we believe that this study with the control groups (that lacked Ser46Phe) showcase the genetic variations of Tat that could be one of the reasons for the decline. 2017 Frontiers in microbiology Discussion HIV S46F 168 176 Tat 213 216 HIV infections 70 84 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. These variants showed less transactivation than TatD60 (with Ser46Phe). 2017 Frontiers in microbiology Discussion HIV S46F 61 69 Tat 48 51 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. We also used two other subtype C variants, TatN12 and TatVT6 (that lacked Ser46Phe) found in the studied population. 2017 Frontiers in microbiology Discussion HIV S46F 74 82 Tat 43 46 28484443 Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction. Wild-type TatC (that lacked Ser46Phe) was used as a reference Tat to compare their differential abilities to interact with TAR and their intracellular protein stability. 2017 Frontiers in microbiology Discussion HIV S46F 28 36 Tat 62 65 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. According to the IAS tables published from 2001 to 2004, the most frequent mutation that we observed for the RT gene-M184V -confers resistance to Zalcitabine, which also appears as the most frequent drug resistance in our analysis (Fig 3). 2017 PloS one Discussion HIV M184V 117 122 RT 109 111 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. Finally, M36I, a PRO mutation whose frequency remained relatively constant over the period of study, in both Puerto Rico and throughout Latin America, influences the flexibility of the protease and its complexed substrate, thereby mediating interactions linked to increased drug resistance. 2017 PloS one Discussion HIV M36I 9 13 PR 185 193 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. Previous research shows that the most common PRO mutation observed in the Puerto Rican sample-L63P -which is estimated to occur in half of drug-naive patients, provides a strong adaptive benefit to HIV viruses replicating under drug pressure. 2017 PloS one Discussion HIV L63P 94 98 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The IAS data also associates M184V with the antiretrovirals Didanosine and Lamivudine, which were the second and third most frequent medications observed for our samples. 2017 PloS one Discussion HIV M184V 29 34 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The predominant RT mutation observed in this study-M184V -is widely considered to be the most critical mutation with respect to resistance to multiple nucleoside and nucleotide analog RT inhibitors (NRTIs). 2017 PloS one Discussion HIV M184V 51 56 NRTI;RT;RT 199;16;184 204;18;186 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The presence of K103N, the second most common RT mutation that we observed, diminishes the efficacy of non-nucleoside analog RT inhibitors (NNRTIs) and, unlike other NNRTI-resistance mutations, persists for a prolonged period of time after the initial viral infection. 2017 PloS one Discussion HIV K103N 16 21 NNRTI;NNRTI;RT;RT 140;166;46;125 146;171;48;127 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The second most frequent PRO mutation that we observed in Puerto Rico-V77I -is considered to be one of the most prominent non-active site mutations implicated in antiretroviral drug resistance. 2017 PloS one Discussion HIV V77I 70 74 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The third most abundant PRO mutation that we observed-I13V -is associated with fast virologic failure and decreased drug affinity. 2017 PloS one Discussion HIV I13V 54 58 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The third most common RT mutation that we observed-M41L -also confers resistance to NRTIs by helping to restore DNA polymerase activity to RT proteins that have been disabled by other mutations. 2017 PloS one Discussion HIV M41L 51 55 Pol;NRTI;RT;RT 116;84;22;139 126;89;24;141 28493944 A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011. The V77I mutation facilitates increased drug resistance by providing conformational flexibility to the enzyme. 2017 PloS one Discussion HIV V77I 4 8 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. Hence any regimen consisting of TDF, AZT or d4T plus 3TC has been shown to be effective in the presence of the M184V mutation, making 3TC a continued drug of choice despite presence of the M184V mutation. 2017 The open microbiology journal Discussion HIV M184V;M184V 111;189 116;194 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. However, the M184V mutation causes increased susceptibility to stavudine (d4T) and TDF, increases the in vitro susceptibility to zidovudine (AZT) and d4T, delays the appearance of TAMs and reduces viral replicative capacity. 2017 The open microbiology journal Discussion HIV M184V 13 18 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. In this study, TAMs observed were M41L, D67N, K70R, L210W, T215Y and K219Q. 2017 The open microbiology journal Discussion HIV D67N;K219Q;K70R;L210W;M41L;T215Y 40;69;46;52;34;59 44;74;50;57;38;64 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. M184V causes high level resistance to 3TC, a drug that is recommended in all 1st and 2nd line ART regimens in Zimbabwe. 2017 The open microbiology journal Discussion HIV M184V 0 5 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. One of the sequences had all TAM-1 mutations, and another had all TAM-2 mutations Table 4 Two of these TAMS: D67N and T215K were also observed in a study recently carried out in Zimbabwe. 2017 The open microbiology journal Discussion HIV D67N;T215K 109;118 113;123 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. Studies have shown TAMs to appear through two pathways in a particular order: TAM-1 (M41L/L210W/T215Y) and TAM-2 (D67N/K70R/T215F/K219Q). 2017 The open microbiology journal Discussion HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 114;130;119;90;85;124;96 118;135;123;95;89;129;101 28553415 Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans. The most frequently occurring mutation was M184V, which was observed in five out of the six sequences (Table 4). 2017 The open microbiology journal Discussion HIV M184V 43 48 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. Drug-specific NNRTIs mutations such as: V179E, K238N and G190E were associated with the selection in patients receiving Nevirapine (NVP) and Efavirenz (EFV) according to Stanford HIVdb program. 2017 PloS one Discussion HIV G190E;K238N;V179E 57;47;40 62;52;45 NNRTI 14 20 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. If we assume that most of the HIV infected donors were not aware of the infection status at donation and didn't receive HIV ART, then some DRMs observed in the present study could be transmitted from the treated HIV infected population, especially for the donor with high drug resistance to NNRTIs due to mutations of G190E and E138A.This hypothesis is yet to be confirmed with more data in future studies. 2017 PloS one Discussion HIV E138A;G190E 328;318 333;323 NNRTI 291 297 HIV infections;HIV infections 30;212 42;224 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. Perhaps a result that some polymorphic accessory mutations such as: A71V/T and L10I/V on PIs; V106I and V90I on NNRTIs, commonly observed in previous studies, were no longer classified as PI minor DRMs and NNRTI resistance mutations in the updated Stanford HIVdb Program Genotypic Resistance Interpretation Algorithm (HIVdb version 8.3). 2017 PloS one Discussion HIV A71T;A71V;L10I;L10V;V106I;V90I 68;68;79;79;94;104 74;74;85;85;99;108 NNRTI;NNRTI;PI;PI 112;206;89;188 118;211;92;190 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. Q58E and M46I mutations, interpreted by the Stanford HIVdb program as non-polymorphic PI-selected mutations, were probably not obtained from domestic transmissions. 2017 PloS one Discussion HIV M46I;Q58E 9;0 13;4 PI 86 88 28622345 The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014. These two drugs were mostly adopted as first-line NNRTIs for anti-retrovirus treatment (ART) in China.While V179D and E138A mutations were described as polymorphic accessory NNRTI-selected mutation, however, it is unclear whether the V179D and E138A mutations have resulted from drug-specific or natural selective pressure by Chinese population. 2017 PloS one Discussion HIV E138A;E138A;V179D;V179D 118;244;108;234 123;249;113;239 NNRTI;NNRTI 50;174 56;179 28649306 Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996-2012. Previous reports in other European countries described the same mutation (T215C/D) circulating domestically. 2017 Infection ecology & epidemiology Discussion HIV T215C;T215D 74;74 81;81 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. 5) are consistent with the B*18-mediated selection and subsequent stable persistence of reverse transcriptase-E138X variants upon transmission, leading them to accumulate in circulating HIV-1 sequences to a degree that mirrors regional HLA-B*18 frequencies. 2017 AIDS (London, England) Discussion HIV E138X 110 115 RT 88 109 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Given that reverse transcriptase-E138X does not affect cabotegravir susceptibility, and assuming that there are no common naturally occurring HIV integrase polymorphisms that confer decreased susceptibility to cabotegravir, it would be sensible to consider this combination as dual PrEP if safe and well tolerated. 2017 AIDS (London, England) Discussion HIV E138X 33 38 RT;IN 11;146 32;155 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Given that rilpivirine PrEP will presumably fail to protect against infection by reverse transcriptase-E138X containing strains, and that these strains occur at appreciable frequencies in areas where HIV-1 prevention efforts are most needed, we strongly advocate that regional molecular epidemiologic surveillance of HIV-1 reverse transcriptase sequence variation be undertaken prior to the selection of antiretrovirals used as HIV-1 prevention, and that rilpivirine not be used as single-agent PrEP in areas with elevated E138X frequencies. 2017 AIDS (London, England) Discussion HIV E138X;E138X 103;523 108;528 RT;RT 81;323 102;344 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Instead, our observations, combined with the lack of in-vitro replicative costs of E138X. 2017 AIDS (London, England) Discussion HIV E138X 83 88 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. It also features the highest natural burden of reverse transcriptase-E138X (6.4% in nearly 10 000 unique treatment-naive sequences examined, with frequencies exceeding 15% in published HIV-1 sequences from Zimbabwe). 2017 AIDS (London, England) Discussion HIV E138X 69 74 RT 47 68 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. It is also notable that the regions where long-acting PrEP has the potential to make the greatest impact on reducing HIV-1 incidence are also the areas where reverse transcriptase-E138X prevalence is highest. 2017 AIDS (London, England) Discussion HIV E138X 180 185 RT 158 179 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Long-acting rilpivirine is currently being evaluated as PrEP in some areas including sub-Saharan Africa, but data from this current and previous studies strongly suggest that rilpivirine will fail to protect against infection by the substantial minority of reverse transcriptase-E138X-containing strains circulating in these areas. 2017 AIDS (London, England) Discussion HIV E138X 279 284 RT 257 278 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Notably, regional reverse transcriptase-E138X frequency correlated positively and significantly with HLA-B*18 frequency in over 40 countries - with subtype C epidemics in sub-Saharan Africa (e.g. 2017 AIDS (London, England) Discussion HIV E138X 40 45 RT 18 39 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Reverse transcriptase-E138K is the most commonly identified mutation upon virologic failure of rilpivirine-containing ART, conferring two to three-fold decreased susceptibility to this drug when present alone; E138A and E138G confer the same level of rilpivirine resistance as E138K. 2017 AIDS (London, England) Discussion HIV E138A;E138G;E138K;E138K 210;220;22;277 215;225;27;282 RT 0 21 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Romania) exhibiting the highest E138X frequencies globally (>15% and nearly 10%, respectively). 2017 AIDS (London, England) Discussion HIV E138X 32 37 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. This observation is unlikely to be explained by confounding by regional rilpivirine use (as use of this drug is negligible in resource-limited settings) or by cross-resistance to other nonnucleoside reverse transcriptase inhibitors (as E138X specifically confers resistance to rilpivirine). 2017 AIDS (London, England) Discussion HIV E138X 236 241 NNRTI 185 220 28650381 Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection. Using large global datasets of linked HIV/HLA genotypes, we demonstrate that E138X variants (most commonly E138A, E138G, or E138K) naturally occur in persons expressing HLA-B*18 allele in the majority of global regions and in most major HIV-1 group M subtypes and CRFs. 2017 AIDS (London, England) Discussion HIV E138A;E138G;E138K;E138X 107;114;124;77 112;119;129;82 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. An initial study by demonstrated the presence of a point mutation at position 77 of HIV-1 Vpr that led to an R77Q substitution with a higher frequency (80 %) in Vpr alleles coming from LTNPs compared with patients developing progressive disease. 2014 JMM case reports Discussion HIV R77Q 109 113 Vpr;Vpr 90;161 93;164 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. Moreover, the Q3R mutation was also present, and this mutation has been described previously in an LTNP patient due to low cytopathic effect. 2014 JMM case reports Discussion HIV Q3R 14 17 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. showed that both the R77Q and Q3R mutants induced G2 arrest but with a lower level of apoptosis when compared with wild-type Vpr. 2014 JMM case reports Discussion HIV Q3R;R77Q 30;21 33;25 Vpr 125 128 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. This was confirmed by, while others were not able to find any association between the R77Q substitution and disease progression. 2014 JMM case reports Discussion HIV R77Q 86 90 28663807 R77Q and Q3R HIV1-VPR mutations in an otherwise asymptomatic 5-year-old child with repeated ear infections. With the case reported here, more clinical evidence of this association is added, as we have described a Vpr R77Q substitution in a mildly symptomatic/asymptomatic HIV-infected child, where all the major HIV-related diseases were absent. 2014 JMM case reports Discussion HIV R77Q 109 113 Vpr 105 108 HIV infections;HIV diseases 164;204 176;224 28679441 HIV-1 genetic diversity and primary drug resistance mutations before large-scale access to antiretroviral therapy, Republic of Congo. Additionally, the sample harboring the mutation T215Y and the TAMs M41L and Y181C sampled at the CHU de Brazzaville (subtype G) was male, but the transmission of these HIV-1 mutations from nevirapine-exposed patients can be suspected. 2017 BMC research notes Discussion HIV M41L;T215Y;Y181C 67;48;76 71;53;81 28679441 HIV-1 genetic diversity and primary drug resistance mutations before large-scale access to antiretroviral therapy, Republic of Congo. For the RT genomic region, the mutations Y215C and M230N were observed at Brazzaville and Pointe-noire, respectively. 2017 BMC research notes Discussion HIV M230N;Y215C 51;41 56;46 RT 8 10 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. The importance of these residues for the IN/Ku70 interactions was also confirmed by cellular experiments showing that overexpressed IN containing mutations E212A and L213A significantly forfeits its ability to bind Ku70. 2017 Scientific reports Discussion HIV E212A;L213A 156;166 161;171 IN;IN 41;132 43;134 28717247 Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting. We showed that substitutions T206A, D207A, Q209A, T210A, K211A, K215A and K219A did not affect the protein binding whereas E212A and L213A substitutions have a severe decreasing effect on complex formation between IN and both Ku70_1-250 and Ku70 but show no influence on the interaction with Ku_251-609 containing the second binding site only. 2017 Scientific reports Discussion HIV D207A;E212A;K211A;K215A;K219A;L213A;Q209A;T206A;T210A 36;123;57;64;74;133;43;29;50 41;128;62;69;79;138;48;34;55 IN 214 216 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Because WT and N74D viruses were identical, except for the point mutation in CA, the selective activity of digoxin was unlikely to have a direct explanation. 2017 PLoS pathogens Discussion HIV N74D 15 19 Capsid 77 79 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. By acutely perturbing cellular gene expression and comparing WT to N74D mutant viruses, we have been able to show that, in CD4+ T-cells, WT HIV-1 has a significant greater preference to integrate into or near genes implicated in T-cell activation and cell metabolism than N74D virus, which has functional consequences at least in the early stages post-infection. 2017 PLoS pathogens Discussion HIV N74D;N74D 67;272 71;276 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Firstly, in normal conditions, WT and N74D viruses have different integration site distributions and we found that WT virus integrates more frequently than N74D virus within or near genes implicated in T-cell activation and cell metabolism, which are highly expressed in activated CD4+ T-cells. 2017 PLoS pathogens Discussion HIV N74D;N74D 38;156 42;160 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Furthermore, our WT and N74D HIV-1 constructs were identical except for the point mutation in CA. 2017 PLoS pathogens Discussion HIV N74D 24 28 Capsid 94 96 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. The degree of proximity of WT and N74D integration sites to heterochromatin located at the nuclear periphery may also be important to determine susceptibility to digoxin. 2017 PLoS pathogens Discussion HIV N74D 34 38 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. The simplest interpretation linking these results together is that WT virus, by virtue of its integration preference, is intrinsically more susceptible than N74D virus to transcriptional perturbations of certain genes (S7 Fig). 2017 PLoS pathogens Discussion HIV N74D 157 161 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. This interpretation is supported by the differential effect of blocking CD40L on WT and N74D viruses, which mimicked digoxin. 2017 PLoS pathogens Discussion HIV N74D 88 92 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. This led us to hypothesize that the integration preference of WT virus makes it more susceptible to digoxin than N74D virus because WT virus would be repressed in tandem with cellular gene expression. 2017 PLoS pathogens Discussion HIV N74D 113 117 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. Using a novel screening approach, we found that digoxin inhibited WT HIV-1 more potently than the N74D mutant virus. 2017 PLoS pathogens Discussion HIV N74D 98 102 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. We confirmed previous studies showing that digoxin represses HIV-1 gene expression, yet WT and N74D viruses share an identical promoter. 2017 PLoS pathogens Discussion HIV N74D 95 99 28727807 Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. We subsequently found that WT HIV-1 integrated within or near those genes more frequently than N74D HIV-1. 2017 PLoS pathogens Discussion HIV N74D 95 99 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. All molecules modulated by S75X and p17R76G, used as input for the Cytoscape ClueGO functional analysis tool to cluster them according to the KEGG biological pathway, result to be related to several known biological pathways. 2017 Scientific reports Discussion HIV S75X 27 31 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. As expected, clonogenic assays showed that the replacement of R to G at position 76, as in S75X, is sufficient to endow refp17 with a B cells growth-promoting activity. 2017 Scientific reports Discussion HIV R76G;S75X 62;91 83;95 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. CD and 2-dimensional NMR spectroscopy confirmed this prediction using a recombinant p17 mutant carrying the single R76G replacement in the refp17 backbone (p17R76G). 2017 Scientific reports Discussion HIV R76G 115 119 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. High-throughput phosphoproteomic and bioinformatics analysis highlighted a central role of Akt kinase in the proliferative signaling pathways induced by S75X and p17R76G in B cells. 2017 Scientific reports Discussion HIV S75X 153 157 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Interestingly, molecules modulated by S75X and p17R76G were also related to the prolactin signaling pathway, supporting previous data showing the presence of higher serum prolactin in HIV+ patients than in healthy individuals and the capability of prolactin to influence normal lymphocyte mitogenesis and lymphoid tumor growth. 2017 Scientific reports Discussion HIV S75X 38 42 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. It is important to underline that molecules modulated by S75X and p17R76G are also involved in signaling triggered by oncogenic viruses, like EBV, HTLV-1 and HBV. 2017 Scientific reports Discussion HIV S75X 57 61 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. MD simulations showed that S75X displays a single aa mutation (R76G) that is likely to be the most responsible for protein destabilization, with reduction of alpha-helical secondary structures and for shifting the equilibrium toward a partially unfolded conformation. 2017 Scientific reports Discussion HIV R76G;S75X 63;27 67;31 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Moreover, the different biological activity of S75X and p17R76G compared to refp17, underlines how the matrix protein binding to and signaling through p17R(s) can potentially involve distinct determinants of structure or conformations. 2017 Scientific reports Discussion HIV S75X 47 51 Matrix 103 109 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. Previously, we showed that in S75X, which contains aa mutations scattered throughout the p17 protein sequence, specific hydrogen bonds stabilizing the refp17 structure are lost, giving rise to a partially unfolded - B-cell growth-promoting - protein. 2017 Scientific reports Discussion HIV S75X 30 34 28747658 A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. The p17R76G protein, similarly to S75X, was also found to activate Akt kinase, modulating PTEN activity. 2017 Scientific reports Discussion HIV S75X 34 38 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. In addition, K103N was shown to cause high level resistance to NVP and EFV, whereas V179D/E led to low level reductions in susceptibility to NVP and EFV. 2017 PloS one Discussion HIV K103N;V179D;V179E 13;84;84 18;91;91 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. In vitro studies have demonstrated that while Y181C/I/V could result in high level resistance to NVP and low level resistance to EFV, G190A led to high level resistance to NVP, and intermediate resistance to EFV. 2017 PloS one Discussion HIV G190A;Y181C;Y181I;Y181V 134;46;46;46 139;55;55;55 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. M184V and Y181C were also the most frequent point mutations conferring resistance to NRTIs and NNRTIs in those patients. 2017 PloS one Discussion HIV Y181C;M184V 10;0 15;5 NNRTI;NRTI 95;85 101;90 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. M184V was identified to be the most frequent mutation conferring resistance to NRTIs. 2017 PloS one Discussion HIV M184V 0 5 NRTI 79 84 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. Previous studies have shown that M184V could result in high level resistance to 3TC and emtricitabine (FTC) and low level resistance to didanosine (ddI) and ABC in vitro. 2017 PloS one Discussion HIV M184V 33 38 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. Second, the I54V and V82A mutations about PIs discovered in the study were not found in patients on second line treatment, but found in two patients who remained on the first line treatment. 2017 PloS one Discussion HIV I54V;V82A 12;21 16;25 PI 42 45 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. Similarly, Y181C, G190A, K103N and V179D/E/F were the most frequent mutations conferring resistance to NNRTIs, and also the most frequent mutations found among patients on ART. 2017 PloS one Discussion HIV G190A;K103N;V179D;V179E;V179F;Y181C 18;25;35;35;35;11 23;30;44;44;44;16 NNRTI 103 109 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. So patients with the M184V mutation could remain 3TC in therapeutic regimen. 2017 PloS one Discussion HIV M184V 21 26 28750025 HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. The present study was the first to identify the PI-resistance mutations I54V and V82A in Shandong, and hence PIs should be carefully selected when we develop treatment regimens for these patients. 2017 PloS one Discussion HIV I54V;V82A 72;81 76;85 PI;PI 48;109 50;112 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Although we could not state categorically the order of emergence of these mutations as this was a cross sectional study, the mutations D67N and K70R were the most frequent single occurring TAMs. 2017 AIDS research and therapy Discussion HIV D67N;K70R 135;144 139;148 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Although, this could likely be related to the reduced usage of d4T, recent reports suggest that compared to other dominant HIV-1 genotypes (subtypes A, CRF02_AG and CRF06cpx), subtype C show the lowest prevalence of M41L DRM. 2017 AIDS research and therapy Discussion HIV M41L 216 220 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. In addition, the high levels of V106M mutations could also be attributed to subtype-specificity, since this mutation had been found most frequently among subtype C. 2017 AIDS research and therapy Discussion HIV V106M 32 37 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. In fact, in the Stanford Drug Resistance database, subtype C strains from drug exposed patients have a higher prevalence of the E138A/K/Q mutation compared to other group M strains (8-9.5% vs. 2017 AIDS research and therapy Discussion HIV E138A;E138K;E138Q 128;128;128 137;137;137 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. In our study, we observed that the four TAMs (D67N, K70R, T215Y and K219Q/E) which make up the Type 2 TAM pathway, occurred more frequently and correlated well with the usage of AZT. 2017 AIDS research and therapy Discussion HIV D67N;K219E;K219Q;K70R;T215Y 46;68;68;52;58 50;75;75;56;63 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. In this study, there was a noticeable absence among subjects of the L210W and very low occurrence of the M41L DRM, both components of the Type 1 TAMs pathway (M41L, L210W and T215Y). 2017 AIDS research and therapy Discussion HIV L210W;L210W;M41L;M41L;T215Y 68;165;105;159;175 73;170;109;163;180 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Our study confirmed the dominance of K65R and V106M, two mutations which are most common among subtype C strains. 2017 AIDS research and therapy Discussion HIV K65R;V106M 37;46 41;51 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Similarly, we speculate that the occurrence of the E138A/K/Q mutation could be due to the codon usage of subtype C RT at this position which is GAA versus GAG in other group M strains. 2017 AIDS research and therapy Discussion HIV E138A;E138K;E138Q 51;51;51 60;60;60 Gag;RT 155;115 158;117 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The absence of M41L and L210W was initially reported from a subtype C cohort in Botswana where the most common TAM pathway was D67N, K70R and T215Y. 2017 AIDS research and therapy Discussion HIV D67N;K70R;L210W;M41L;T215Y 127;133;24;15;142 131;137;29;19;147 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The high occurrence of both K103N and V106M could be a reflection of the wide use of EFV and NVP as part of the first line therapy. 2017 AIDS research and therapy Discussion HIV K103N;V106M 28;38 33;43 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The M184V mutation was the most prevalent DRM, observed in 52% of study subjects. 2017 AIDS research and therapy Discussion HIV M184V 4 9 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The mutations V106A/M and Y181C were 13.3 and 4.8% more common in Pretoria than in Limpopo, respectively. 2017 AIDS research and therapy Discussion HIV V106A;V106M;Y181C 14;14;26 21;21;31 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The selection of TAMs such as D67N, M41L and T215Y could be attributed to treatment with the thymidine analogues AZT and d4T, which also cause cross resistance to other NRTIs. 2017 AIDS research and therapy Discussion HIV D67N;M41L;T215Y 30;36;45 34;40;50 NRTI 169 174 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. The use of nevirapine monotherapy could have potentially impacted on the observed level of NNRTI mutations particularly K103N. 2017 AIDS research and therapy Discussion HIV K103N 120 125 NNRTI 91 96 28750647 High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. Three viral RNA and two proviral DNA derived sequences from patients who had never been treated with ddI, ABC, or TDF harboured a K65R mutation. 2017 AIDS research and therapy Discussion HIV K65R 130 134 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Here, six of the patients harboured E138 substitutions, three of whom had E138A. 2017 Journal of the International AIDS Society Discussion HIV E138A 74 79 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. However, studies do monitor this location, especially the E138A substitution inhibiting rilpivirine, whose prevalence has been shown to vary by geographical region and HIV-1 subtype; in Europe, it was identified in 3.1% of the recently infected patients. 2017 Journal of the International AIDS Society Discussion HIV E138A 58 63 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. K103N is considered to have a limited effect on viral fitness and, therefore, can be continuously transmitted as a major mutation that dominates the viral pool and impacts future therapy. 2017 Journal of the International AIDS Society Discussion HIV K103N 0 5 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. M184V, frequently observed in patients failing therapy, which is regarded as a mutation that reduces viral fitness more than any other NRTI mutation, may wane over time, likely as a consequence of reversion to the wild-type sequence. 2017 Journal of the International AIDS Society Discussion HIV M184V 0 5 NRTI 135 139 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. Moreover, in the two cases treated with antivirals that could potentially be affected by the identified minor TDRM (NRTI K65R), treatment was successful. 2017 Journal of the International AIDS Society Discussion HIV K65R 121 125 NRTI 116 120 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. The high frequency (>20% of the viral population) NRTI M184V and T215S and NNRTI K103N mutations identified here in several cases, have already been reported to be primarily confined to recently identified patients diagnosed in more recent years. 2017 Journal of the International AIDS Society Discussion HIV K103N;M184V;T215S 81;55;65 86;60;70 NNRTI;NRTI 75;50 80;54 28799325 Comparison between next-generation and Sanger-based sequencing for the detection of transmitted drug-resistance mutations among recently infected HIV-1 patients in Israel, 2000-2014. The T215S mutation, restricted here to subtype B, was one of the most commonly observed TDRM in this subtype in the UK and was reported to persist in the viral quasispesies for many years. 2017 Journal of the International AIDS Society Discussion HIV T215S 4 9 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. Furthermore, to understand the role of Ser46Phe in TatD60 on TAR interaction, we carried out molecular docking of Tat variants with TAR. 2017 Frontiers in microbiology Discussion HIV S46F 39 47 Tat;Tat 51;114 54;117 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. In TatD60, Ser46Phe produced steric hindrance that led to the exposure of cysteine-rich, core and glutamine-rich regions, allowing additional residues to interact with TAR. 2017 Frontiers in microbiology Discussion HIV S46F 11 19 Tat 3 6 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. TatD60 interacted with TAR more efficiently than other TatC which could likely be due to the presence of the Ser46Phe and Ser61Arg mutations. 2017 Frontiers in microbiology Discussion HIV S46F;S61R 109;122 117;130 Tat 0 3 28848502 In silico Analyses of Subtype Specific HIV-1 Tat-TAR RNA Interaction Reveals the Structural Determinants for Viral Activity. TatN12 showed a lower or similar level of transactivation and a weaker interaction with TAR than TatC, it appears that Gly44Ser in TatN12 led to the formation of intermolecular H-bonds between Ser44 and Arg49 that hinder the interaction of Arg49 with TAR. 2017 Frontiers in microbiology Discussion HIV G44S 119 127 Tat;Tat 0;131 3;134 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). A total of 80 participants had the NRTI-associated substitution A62V at baseline, detected by either population or deep sequencing. 2017 HIV clinical trials Discussion HIV A62V 64 68 NRTI 35 39 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). A62V is a known polymorphism in Russia and has been previously described as a fitness compensatory mutation associated with K65R. 2017 HIV clinical trials Discussion HIV K65R;A62V 124;0 128;4 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Finally, though A62V is a known polymorphism that has previously been described as a fitness compensatory mutation associated with K65R, there was no evidence that the presence of A62V predisposed participants to developing K65R. 2017 HIV clinical trials Discussion HIV A62V;A62V;K65R;K65R 16;180;131;224 20;184;135;228 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Four participants had the exclusion mutation M184I at low levels by deep sequencing, and 3 of these participants were virologic successes at Week 48, and one participant was lost to follow up with the last available HIV-1 RNA <50 copies/mL. 2017 HIV clinical trials Discussion HIV M184I 45 50 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Outcome analyses were done for other resistance mutations seen at baseline, including the NNRTI-associated substitutions K103N and E138A/G/K/Q/R, and the PI-associated substitutions M46I/L and L33F, and similar results were observed. 2017 HIV clinical trials Discussion HIV E138A;E138G;E138K;E138Q;E138R;K103N;L33F;M46I;M46L 131;131;131;131;131;121;193;182;182 144;144;144;144;144;126;197;188;188 NNRTI;PI 90;154 95;156 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Secondary IN resistance substitutions such as S119P and M50I were observed in greater than 50% of participants by deep sequencing, and these participants had HIV-1 RNA <50 copies/mL at Week 48 at proportions similar to the overall population, and no development of IN resistance. 2017 HIV clinical trials Discussion HIV M50I;S119P 56;46 60;51 IN;IN 10;265 12;267 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Ten participants treated with EVG/COBI/FTC/TDF had the polymorphic primary IN resistance substitution T97A by deep sequencing, and all of these participants had <50 copies/mL HIV-1 RNA at Week 48. 2017 HIV clinical trials Discussion HIV T97A 102 106 IN 75 77 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The most common NNRTI-associated substitutions were V90I and E138A/G/K/Q/R, observed most frequently in subtypes A and A1, but these did not impact genotypic sensitivity to most NNRTIs. 2017 HIV clinical trials Discussion HIV E138A;E138G;E138K;E138Q;E138R;V90I 61;61;61;61;61;52 74;74;74;74;74;56 NNRTI;NNRTI 16;178 21;184 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The most common pre-existing NRTI-associated substitution was A62V, observed in 13.6% of participants, all located in Russia and all with subtypes A or A1. 2017 HIV clinical trials Discussion HIV A62V 62 66 NRTI 29 33 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The primary efavirenz resistance substitution K103N was present in 3.0% of women, mostly with subtype B and located in the United States. 2017 HIV clinical trials Discussion HIV K103N 46 51 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). The three ATV+RTV+FTC/TDF participants who developed M184V/I by population sequencing also had this resistance substitution by deep sequencing at the failure time point, and no additional resistance substitutions to study drug were detected by deep sequencing that were not detected by population sequencing. 2017 HIV clinical trials Discussion HIV M184I;M184V 53;53 60;60 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). There was only one virologic failure sample with a sequencing discrepancy; the NNRTI resistance substitution K101E was detected by deep sequencing at 23.1% in one sample but was not detected by population sequencing. 2017 HIV clinical trials Discussion HIV K101E 109 114 NNRTI 79 84 28891788 Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128). Therefore, A62V might predispose participants to developing K65R; however, no participant in this study developed this TDF resistance mutation. 2017 HIV clinical trials Discussion HIV A62V;K65R 11;60 15;64 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. 2C) and was supported by Y2H analysis and data regarding oligomatic formation, tRNALys3 packaging level and reverse transcription using M6 GAPDH. 2016 Biochemistry and biophysics reports Discussion HIV Y2H 25 28 RT 108 129 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. Furthermore, we tried to prepare mutant pNL-CH proviral clones encoding R58E/Q59A/Q63A in MA and E76R/R82E in CA to clarify the effects of these mutations on tRNALys3 incorporation. 2016 Biochemistry and biophysics reports Discussion HIV Q59A;Q63A;R58E;E76R;R82E 77;82;72;97;102 81;86;76;101;106 Matrix;Capsid 90;110 92;112 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. However, we did not examine whether the tRNALys3 incorporation level inside virions was increased because the mutational introduction within the capsid-coding gene (E76R, R82E) impaired HIV-1 budding (data not shown). 2016 Biochemistry and biophysics reports Discussion HIV E76R;R82E 165;171 169;175 Capsid 145 151 28955972 The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNA(Lys3) packaging into human immunodeficiency virus type-1 particles. On the other hand, Y2H analysis demonstrated that the R58E, Q59A or Q63A of MA, and E76R or R82E of CA-NTD mutants abrogated their interaction with the C-terminal domain of GAPDH. 2016 Biochemistry and biophysics reports Discussion HIV E76R;Q59A;Q63A;R58E;R82E;Y2H 84;60;68;54;92;19 88;64;72;58;96;22 Matrix;Capsid 76;100 78;102 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. For NNRTIs the most common mutated sequence was reported to be K103N that is similar to the findings of other studies. 2017 Iranian journal of public health Discussion HIV K103N 63 68 NNRTI 4 10 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. G73SC mutation is associated with reduced susceptibility to nelfinavir and saquinavir. 2017 Iranian journal of public health Discussion HIV G73C;G73S 0;0 5;5 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. Hence, we recommend more studies to investigate the distribution of I47VA mutation at national level to help with development of treatment guidelines. 2017 Iranian journal of public health Discussion HIV I47A;I47V 68;68 73;73 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. I47VA confers high-level resistance to lopinavir and fosamprenavir; as well low/intermediate-resistance to the remaining PIs expect for atazanaavir and saquinavir. 2017 Iranian journal of public health Discussion HIV I47A;I47V 0;0 5;5 PI 121 124 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. Kaletra (lopinavir/ritronavir) was the main PI prescribed to patients in our country; hence, we predict treatment failure to be seen among patients with I47VA mutation. 2017 Iranian journal of public health Discussion HIV I47A;I47V 153;153 158;158 PI 44 46 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. On the other side, G73SC and I47VA were common mutations seen for PIs. 2017 Iranian journal of public health Discussion HIV G73C;G73S;I47A;I47V 19;19;29;29 24;24;34;34 PI 66 69 29026792 Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. The frequency of M184V mutation, as the major cause of high-level drug resistance to NRTIs, was more commonly observed than other mutations similar to the findings of other studies. 2017 Iranian journal of public health Discussion HIV M184V 17 22 NRTI 85 90 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. But on the other side, a stable rate of selection was also observed for some NRTI mutations (such as Y115F, L210W) and several NNRTI mutations (such as L100I, K101E, P225H and M230L). 2017 PloS one Discussion HIV K101E;L100I;L210W;M230L;P225H;Y115F 159;152;108;176;166;101 164;157;113;181;171;106 NNRTI;NRTI 127;77 132;81 29049402 Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade longitudinal study. Lastly, the study in one side identified an increasing common mutational pathways overtime with two thymidine non-analog (M184V and K65R) and three thymidine analog (D67N, K70R and K219E) major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) which is consistent with previous studies. 2017 PloS one Discussion HIV D67N;G190A;K103N;K219E;K65R;K70R;M184V;V106M;Y181C 166;312;298;181;132;172;122;323;305 170;317;303;186;136;176;128;328;310 NRTI;NNRTI;NRTI 194;275;238 226;280;242 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Gag sequences from 12 of the 137 subjects analyzed in this study, 10 of whom were infected with HIV-1 CRF02_AG, showed >=3 mutations in the Gag P2/NC cleavage site, including S373Q/T/A, A374T/S/G/N, T375S/A/N/G, I376V, and G381S. 2017 Scientific reports Discussion HIV A374G;A374N;A374S;A374T;G381S;I376V;S373A;S373Q;S373T;T375A;T375G;T375N;T375S 186;186;186;186;223;212;175;175;175;199;199;199;199 197;197;197;197;228;217;184;184;184;210;210;210;210 Gag;Gag;NC 0;140;147 3;143;149 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. In addition to the resistance mutations to NRTIs (M184V and the TAM T215F) and NNRTIs (L100I, Y181C, K103N, V108I, and Y188L) observed in naive subjects, these subjects on ART also had the TAMs D67N, K70R, and K219Q; and 9 of those 11 subjects had major resistance mutations to both NRTIs and NNRTIs. 2017 Scientific reports Discussion HIV D67N;K103N;K219Q;K70R;L100I;M184V;T215F;V108I;Y181C;Y188L 194;101;210;200;87;50;68;108;94;119 198;106;215;204;92;56;73;113;99;124 NNRTI;NNRTI;NRTI;NRTI 79;293;43;283 85;299;48;288 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. In the current study, analysis of RT and protease sequences from 109 HIV-infected and treatment-naive Cameroonians showed 8 (7.3%) with transmitted DRMs, including major resistance mutations to NRTIs (M184V and T215F) and NNRTIs (L100I, Y181C, K103N, V108I, and Y188L). 2017 Scientific reports Discussion HIV K103N;L100I;M184V;T215F;V108I;Y181C;Y188L 244;230;201;211;251;237;262 249;235;207;216;256;242;267 PR;NNRTI;NRTI;RT 41;222;194;34 49;228;199;36 HIV infections 69 81 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. M184V mutation reduces the incorporation of nucleotide analogs into DNA, resulting in increased resistance to 3TC and emtricitabine. 2017 Scientific reports Discussion HIV M184V 0 5 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. M184V was the most common NRTIs resistant mutation in both treatment-naive and subjects on ART. 2017 Scientific reports Discussion HIV M184V 0 5 NRTI 26 31 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. Other studies of subjects infected with HIV-1 subtypes B, A, C, G, and D, showed that mutations in Gag associated with resistance to PIs (LPV, and SQV/r) and treatment failure included mutations at amino acid residues 373 (including S373Q/P), 374, 375, and 378 at the P2/NC cleavage site. 2017 Scientific reports Discussion HIV S373P;S373Q 233;233 240;240 Gag;NC;PI 99;271;133 102;273;136 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. The major NNRTIs resistance mutations identified in both treatment-naive and subjects on ART included L100I, Y181C, K103N, V108I, and Y188L. 2017 Scientific reports Discussion HIV K103N;L100I;V108I;Y181C;Y188L 116;102;123;109;134 121;107;128;114;139 NNRTI 10 16 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. The TAMs T215F, D67N, K70R, and K219Q induce resistance to the thymidine analogues AZT, stavudine, and other NRTIs by enhancing ATP-mediated excision and hydrolytic removal of the drug incorporated into viral DNA, thereby unblocking the viral DNA chain and enabling continuation of viral replication. 2017 Scientific reports Discussion HIV D67N;K219Q;K70R;T215F 16;32;22;9 20;37;26;14 NRTI 109 114 29074854 Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon. These subjects also had secondary mutations in the protease, including K20I that was previously shown to be associated with failure of PIs-based ART when simultaneously present with mutations in the Gag amino acids residues 373, 374, and/or 375. 2017 Scientific reports Discussion HIV K20I 71 75 PR;Gag;PI 51;199;135 59;202;138 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. (2016) also observed a prevalence increase of E529D following treatment administration in subtype C patients in Brazil, further supporting our findings. 2017 Viruses Discussion HIV E529D 46 51 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. However, the exact role of E529D needs to be further investigated using site-directed mutagenesis as this mutation can either increase phenotypic resistance or restore enzymatic activity. 2017 Viruses Discussion HIV E529D 27 32 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. In combination with TAMs and A371V, Q509L mutation reduced AZT susceptibility about 10- to 50-fold in vitro. 2017 Viruses Discussion HIV A371V;Q509L 29;36 34;41 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. In our cohort, the E529D mutation was significantly more prevalent in sequences from NRTI treated patients, suggesting that it is a treatment related mutation in South African subtype C viruses. 2017 Viruses Discussion HIV E529D 19 24 NRTI 85 89 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. None of the resistance-associated mutations in RNase H (L469F, K527N, Q509L and K558E/R) identified for subtype B were found to be significant among treated compared to naive participants in this cohort. 2017 Viruses Discussion HIV K527N;K558E;K558R;L469F;Q509L 63;80;80;56;70 68;87;87;61;75 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Phylogenetic analyses indicated that the emergence of E529D patients did not result from a shared ancestry but rather from multiple independent selection events. 2017 Viruses Discussion HIV E529D 54 59 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. The presence of RNase H mutation E529D was directly dependent on whether or not the patient received an NRTI, supporting its role in the development of NRTI resistance. 2017 Viruses Discussion HIV E529D 33 38 NRTI;NRTI 104;152 108;156 29117130 Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals. Unfortunately, this study was unable to directly link the presence of E529D with a specific antiretroviral drug since we could not differentiate d4T from AZT users within the treated group. 2017 Viruses Discussion HIV E529D 70 75 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. A key finding of our report is the influence of the L33F mutation on the open active site and on the S1/S1' subsites through anchoring of the 30s and 80s loops independent of space group. 2015 Biochemistry and biophysics reports Discussion HIV L33F 52 56 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. As a result, noncovalent interactions are increased in this region compared to the WT, causing the L33F to act as a molecular anchor. 2015 Biochemistry and biophysics reports Discussion HIV L33F 99 103 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Despite structural and symmetry differences between the aforementioned and this report, our results regarding L33F as a molecular anchor are consistent with the previous reports by the the Schiffer and Konvalinka groups. 2015 Biochemistry and biophysics reports Discussion HIV L33F 110 114 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Enhanced molecular anchoring by the L33F mutation reduces the flexibility of the 30s and 80s loops, thereby inhibiting proper formation of the S1/S1' subsite and keeping the active site in an open conformation in the MDR769 L33F-DRV complex. 2015 Biochemistry and biophysics reports Discussion HIV L33F 36 40 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. In conclusion, for the first time we here report the molecular mechanisms by which the nonpolymorphic PR mutation L33F contributes to DRV resistance. 2015 Biochemistry and biophysics reports Discussion HIV L33F 114 118 PR 102 104 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. In contrast, the Weber group and this report describe the L33F DRV complex as a structure with open protease flaps when the structures were solved in P41212. 2015 Biochemistry and biophysics reports Discussion HIV L33F 58 62 PR 100 108 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. Other research groups such as the Schiffer group and the Konvalinka group have previously reported L33F DRV complexes with the flaps in a closed conformation by solving the structures in P212121 (PDB ID:4QY1) and P61 (PDB ID:3GGU), respectively. 2015 Biochemistry and biophysics reports Discussion HIV L33F 99 103 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The Konvalinka group (closed protease flaps) suggests that L33F is possibly implicated in structural changes in the flap and flap hinge regions of PR. 2015 Biochemistry and biophysics reports Discussion HIV L33F 59 63 PR;PR 29;147 37;149 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The L33F mutation is selected in patients receiving a DRV/r regimen, and is associated with reduced response to DRV/r treatment as it has direct influence on the inhibitor-interacting residues. 2015 Biochemistry and biophysics reports Discussion HIV L33F 4 8 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The L33F mutation may contribute to resistance via two mechanisms: one, by restoring noncovalent interactions lost due to other primary mutations, and two, by further reducing interactions between DRV and active site residues. 2015 Biochemistry and biophysics reports Discussion HIV L33F 4 8 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The larger side chain of L33F embeds further into the hydrophobic pocket than L33, the latter of which is present in both WT and MDR769 structures. 2015 Biochemistry and biophysics reports Discussion HIV L33F 25 29 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The majority of these HIV PR L33F DRV complexes have been solved with the flaps in a closed conformation. 2015 Biochemistry and biophysics reports Discussion HIV L33F 29 33 PR 26 28 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The results of these simulations support the hypothesis that L33F may play a role as a molecular anchor within HIV-1 protease. 2015 Biochemistry and biophysics reports Discussion HIV L33F 61 65 PR 117 125 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The structure of the L33F DRV complex reported here shows the protease flaps in an open conformation. 2015 Biochemistry and biophysics reports Discussion HIV L33F 21 25 PR 62 70 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. The Weber group (PDB ID:4NPT) also utilized the inactivating mutation D25N to facilitate HIV PR expression, purification, and crystallization. 2015 Biochemistry and biophysics reports Discussion HIV D25N 70 74 PR 93 95 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. This report describes the effects of L33F on the structure of HIV protease as well as the effect it has on inhibitor recognition. 2015 Biochemistry and biophysics reports Discussion HIV L33F 37 41 PR 66 74 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. To date, all deposited structures of HIV PR L33F complexes have been solved in three different space groups: P212121, P61, and P41212. 2015 Biochemistry and biophysics reports Discussion HIV L33F 44 48 PR 41 43 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. We propose that modifications to the P1/P1' groups of existing PIs to fill the open S1/S1' subsite might result in a greater response by patients who harbor the L33F mutation in HIV-PR. 2015 Biochemistry and biophysics reports Discussion HIV L33F 161 165 PI;PR 63;182 66;184 29124158 The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops. With specific regard to the L33F mutation, the Schiffer group (closed protease flaps) reports L33F may play a role in active site expansion. 2015 Biochemistry and biophysics reports Discussion HIV L33F;L33F 28;94 32;98 PR 70 78 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. As levels of acquired HIVDR are higher to NNRTIs (32%) compared to NRTIs (29%), conferring high-level resistance to NVP and EFV (mainly due to K103N and Y181C), NRTIs are more prone for use in second-line combinations in such ART program. 2017 BMC research notes Discussion HIV K103N;Y181C 143;153 148;158 NNRTI;NRTI;NRTI 42;67;161 48;72;166 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Complementary studies are needed to ascertain response after switch from first- to second-line, to evaluate the feasibility of point-of-care resistance testing designed with commonly found mutations (M184V/I, T215mutants, K103N, Y181C) for greater cost-effectiveness, and monitoring HIVDR early warning indicators. 2017 BMC research notes Discussion HIV K103N;M184I;M184V;Y181C 222;200;200;229 227;207;207;234 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Even though 3TC and FTC are highly hampered by M184V (~ 29%) in the overall study population, the ability of this mutation in decreasing viral replicative fitness and in improving susceptibility to thymidine analogs suggest maintaining these drugs (3TC and FTC) within current treatment guidelines. 2017 BMC research notes Discussion HIV M184V 47 52 29126456 Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N'Djamena, Chad: findings from a cross-sectional study. Of note, K65R, the main DRM to TDF was not detected, supporting TDF-containing NRTIs as preferred combinations to second-line LPV/r, as globally recommended. 2017 BMC research notes Discussion HIV K65R 9 13 NRTI 79 84 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Additionally, in this present work, the amino acid substitution P58S was observed in HCV GT-1b sequences from HCV-monoinfected and HCV/HIV-coinfected patients. 2017 BMC infectious diseases Discussion HIV P58S 64 68 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Finally, in GT-3a sequences from monoinfections, the Y93H and A30K substitutions were present at low to moderate frequencies. 2017 BMC infectious diseases Discussion HIV A30K;Y93H 62;53 66;57 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. In regard to HCV/HIV-coinfected patients enrolled in this study, M28 T and Q30H/R variants were found in GT-1a isolates and may confer variable levels of resistance depending on the approved NS5A inhibitors used. 2017 BMC infectious diseases Discussion HIV M28T;Q30H;Q30R 65;75;75 70;81;81 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. In sequences from GT-1b-monoinfected patients, the RASs L31F/V and Y93H were observed. 2017 BMC infectious diseases Discussion HIV L31F;L31V;Y93H 56;56;67 62;62;71 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. In this study, the amino acid substitutions M28 V and Q30H/R were observed within the GT-1a sequences from monoinfected patients. 2017 BMC infectious diseases Discussion HIV M28V;Q30H;Q30R 44;54;54 49;60;60 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Moreover, GT-1b isolates were found with the Y93H substitution, which is associated with resistance to daclatasvir, ombitasvir, and elbasvir (24-93-fold), as well as ledipasvir (>1000-fold). 2017 BMC infectious diseases Discussion HIV Y93H 45 49 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. observed that A30K and Y93H variants in NS5A reduce viral sensitivity to daclatasvir and ledipasvir, respectively. 2017 BMC infectious diseases Discussion HIV A30K;Y93H 14;23 18;27 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Previously published work has shown that M28 V confers low-level resistance to ombitasvir, while Q30H/R confers high-level resistance to daclatasvir, ledipasvir, and ombitasvir (fold change >100). 2017 BMC infectious diseases Discussion HIV M28V;Q30H;Q30R 41;97;97 46;103;103 29132303 Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil. Y93H confers different levels of resistance to approved NS5A inhibitors, including elbasvir and velpatasvir. 2017 BMC infectious diseases Discussion HIV Y93H 0 4 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. For subtype A1, E138A LTNs:except that from the E138A_4:were founded more than 15 years ago in contrast to the more recent K103N LTN, suggesting that the E138A resistance network expanded many years before the use of rilpivirine in clinical practice. 2017 Genes Discussion HIV E138A;E138A;E138A;K103N 16;154;48;123 21;159;53;128 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Notably, with regard to Re trends, we found the opposite, where the more recent LTNs (K103N & E138A_4) were declining or remained stable over the last few years (Re < 1, or Re = 1), versus E138A LTNs 1, 2, and 3, which continue to expand (Re > 1). 2017 Genes Discussion HIV E138A;E138A;K103N 189;94;86 194;99;92 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. These differences could be due to the higher risk behavior of the individuals infected with K103N and E138A_4, compared to those found within the E138A LTNs 1, 2, and 3. 2017 Genes Discussion HIV E138A;E138A;K103N 146;102;92 151;107;97 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. These findings suggest that resistance mutations with low fitness cost such as E138A can be propagated in the absence of drug-selective pressure as a result of onward transmissions among treatment-naive individuals. 2017 Genes Discussion HIV E138A 79 84 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. Transmission dynamics showed that the more recent LTNs (K103N and E138A_4) initially expanded at higher rates (higher slope and Re) than those with earlier tMRCA. 2017 Genes Discussion HIV E138A;K103N 66;56 71;62 29137167 Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naive Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health. We focused on subtype A1, since dominant resistant viruses spreading to major LTNs (N > 6 individuals) belonged only to this subtype, except from the E138Q LTN found among people who inject drugs as analyzed previously. 2017 Genes Discussion HIV E138Q 150 155 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. A time trend in frequency was observed for variants T125A, D256E, and A265V. 2017 Virology journal Discussion HIV A265V;D256E;T125A 70;59;52 75;64;57 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. All of them occurred within the same biochemical class of amino acids, with the exception of T125A that represents a switch from a hydrophilic to a hydrophobic amino acid. 2017 Virology journal Discussion HIV T125A 93 98 29137637 Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. The most frequent substitutions were T125A, V165I, I220L, S230 N, D232E, L234I, D256E, and A265V. 2017 Virology journal Discussion HIV A265V;D232E;D256E;I220L;L234I;S230N;T125A;V165I 91;66;80;51;73;58;37;44 96;71;85;56;78;64;42;49 29156603 Adding an Artificial Tail-Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile. Among all the resistant mutations in the gp41 of the 19 HIV-1-resistant strains we tested, only L34S and D36G mutations are located in the target pocket of the IDL-anchor. 2017 Molecules (Basel, Switzerland) Discussion HIV D36G;L34S 105;96 109;100 gp41 41 45 29156603 Adding an Artificial Tail-Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile. For example, Q79E and K90E mutations are located in the gp41 loop domain known to interact with gp120. 2017 Molecules (Basel, Switzerland) Discussion HIV K90E;Q79E 22;13 26;17 gp120;gp41 96;56 101;60 29156603 Adding an Artificial Tail-Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile. For example, substitution N126K in the gp41 CHR domain has been reported to cause resistance to several HIV-1 drugs. 2017 Molecules (Basel, Switzerland) Discussion HIV N126K 26 31 gp41 39 43 29156603 Adding an Artificial Tail-Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile. Here, we found that HP23-E6-IDL could still inhibit HIV-1 variants with N126K, Q79E/N126K, K90E/N126K, E49K/N126K, and D36G/E49K/N126K mutations, proving its high affinity to the prehairpin intermediate of gp41. 2017 Molecules (Basel, Switzerland) Discussion HIV D36G;E49K;N126K;E49K;K90E;N126K;N126K;N126K;N126K;Q79E 119;124;129;103;91;72;84;96;108;79 123;128;134;107;95;77;89;101;113;83 gp41 206 210 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Allosteric changes noted in NMR observables of the CA domain suggest that structural changes in the lattice of CA-SP1(T8I), which mimics the MI-bound form, play important roles. 2017 Nature communications Discussion HIV T8I 118 121 SP1;Capsid;Capsid 114;51;111 117;53;113 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Another noteworthy result is the atomic level understanding of the effects caused by BVM binding and the T8I mutation in SP1 on the structure and dynamics of CA-SP1. 2017 Nature communications Discussion HIV T8I 105 108 SP1;SP1;Capsid 121;161;158 124;164;160 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Another surprising effect of the T8I mutation is the degree of allosteric modulation imparted on the conformation and dynamics of CA, affecting both domains, NTD and CTD. 2017 Nature communications Discussion HIV T8I 33 36 Capsid 130 132 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Chemical shift changes due to the presence of the T8I mutation are also observed throughout the CTD. 2017 Nature communications Discussion HIV T8I 50 53 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Furthermore, replication defects resulting from PF96-dependent resistance mutations in the MHR can be compensated for by mutations in the CTD tail or SP1 subdomain (such as T8I), suggesting that an allosteric "cross-talk" between the SP1 peptide and MHR may exist. 2017 Nature communications Discussion HIV T8I 173 176 SP1;SP1 150;234 153;237 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Importantly, the motions we detected and quantified are an inherent feature of SP1 encoded by the primary sequence of the peptide rather than the morphology of the assembly, as is evident from the comparison of WT and the T8I mutant of SP1, and similar to the motions found in other subdomains of CA. 2017 Nature communications Discussion HIV T8I 222 225 SP1;SP1;Capsid 79;236;297 82;239;299 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In contrast to CA-SP1(T8I), the SP1 subdomain of WT CA-SP1 exists in a highly dynamic helix-coil equilibrium, as shown by MAS NMR, cryo-EM, and MD studies. 2017 Nature communications Discussion HIV T8I 22 25 SP1;SP1;SP1;Matrix;Capsid;Capsid 18;32;55;122;15;52 21;35;58;124;17;54 29176596 Quenching protein dynamics interferes with HIV capsid maturation. In contrast, CA-SP1 assemblies without the T8I mutation exhibited increased dynamics in the CypA loop, compared to the corresponding CA assemblies, possibly indicating that NTD-NTD contacts may be altered by this SP1 mutation. 2017 Nature communications Discussion HIV T8I 43 46 SP1;SP1;Capsid;Capsid 16;213;13;133 19;216;15;135 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Interestingly, a similar, same order of magnitude reduction of loop dynamics was previously observed in the A92E and G94D escape mutants of CA. 2017 Nature communications Discussion HIV A92E;G94D 108;117 112;121 Capsid 140 142 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Our data reveal that the conformation and dynamics of diverse regions in CA-SP1(T8I) differ from the WT CA lattice, both in the NTD, such as the CypA loop and loop 6/7, as well as the CTD, for instance the MHR. 2017 Nature communications Discussion HIV T8I 80 83 SP1;Capsid;Capsid 76;73;104 79;75;106 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Overall, the perturbations we observe in the CA-SP1(T8I) assemblies suggest that MI binding affects the structure of those CTD regions that undergo critical conformational rearrangements during maturation. 2017 Nature communications Discussion HIV T8I 52 55 SP1;Capsid 48;45 51;47 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Remarkably, the MAS NMR experiments unequivocally show that nano- to microsecond timescale dynamics of the CypA loop are dramatically attenuated in assemblies of the CA-SP1(T8I) mutant, as evidenced by significantly increased 1H-15N dipolar order parameters compared to those in WT CA assemblies of the same NL4-3 strain. 2017 Nature communications Discussion HIV T8I 173 176 SP1;Matrix;Capsid;Capsid 169;16;166;282 172;18;168;284 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Significant structural differences are observed at the CTD-SP1 junction upon BVM binding, with affected residues becoming restricted in motions and exhibiting increased helical propensity in the maturation-inhibiting CA-SP1(T8I) mutant, compared to WT CA-SP1 assemblies. 2017 Nature communications Discussion HIV T8I 224 227 SP1;SP1;SP1;Capsid;Capsid 59;220;255;217;252 62;223;258;219;254 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Similarly, the N-terminal beta-hairpin is stabilized in the CA-SP1(T8I) assemblies, compared to WT CA assemblies. 2017 Nature communications Discussion HIV T8I 67 70 SP1;Capsid;Capsid 63;60;99 66;62;101 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Specifically, the T8I mutation introduces increased conformational and dynamic heterogeneity (multiple conformers are detected) into the highly conserved MHR region (Supplementary Figs. 2017 Nature communications Discussion HIV T8I 18 21 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Taken together, the MAS NMR results clearly show that in assembled CA-SP1(T8I), the conformation of the NTD is different compared to WT CA-SP1 or WT CA assemblies. 2017 Nature communications Discussion HIV T8I 74 77 SP1;SP1;Matrix;Capsid;Capsid;Capsid 70;139;20;67;136;149 73;142;22;69;138;151 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The most pronounced effect of the T8I mutation which mimics BVM binding, is greatly attenuated dynamics and increased helicity of residues H226(CA)-Q6(SP1), which form a contiguous helix in the mutant. 2017 Nature communications Discussion HIV T8I 34 37 SP1;Capsid 151;144 154;146 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The observations of dramatic chemical shift changes and altered dynamics in the NTD for CA-SP1(T8I) are rather surprising, since CA-SP1 HXB2 and CA(A92E)-SP1 exhibit much smaller chemical shift changes in the NTD compared to CA HXB2 and CA(A92E), respectively. 2017 Nature communications Discussion HIV A92E;A92E;T8I 148;240;95 152;244;98 SP1;SP1;SP1;Capsid;Capsid;Capsid;Capsid;Capsid 91;132;154;88;129;145;225;237 94;135;157;90;131;147;227;239 29176596 Quenching protein dynamics interferes with HIV capsid maturation. The T8I mutation also induces significant chemical shift changes for residues in loop 6/7, mutations of which affect HIV-1 replication. 2017 Nature communications Discussion HIV T8I 4 7 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Therefore, the T8I mutation and, by virtue of its phenocopying effect, BVM and related MIs may influence regions that undergo critical conformational rearrangements during maturation. 2017 Nature communications Discussion HIV T8I 15 18 29176596 Quenching protein dynamics interferes with HIV capsid maturation. This loop resides at the trimer interface in the immature lattice, and the T8I-induced chemical shift changes may suggest the presence of altered trimer interface contacts. 2017 Nature communications Discussion HIV T8I 75 78 29176596 Quenching protein dynamics interferes with HIV capsid maturation. Thus, the T8I mutation has a larger influence on the NTD conformation than the presence of the SP1 peptide alone. 2017 Nature communications Discussion HIV T8I 10 13 SP1 95 98 29176596 Quenching protein dynamics interferes with HIV capsid maturation. To conclude, assessing the conformational effects of BVM binding and dynamics changes in the maturation-inhibiting CA-SP1(T8I) mutant led to important mechanistic insights into SP1 cleavage inhibition by MIs. 2017 Nature communications Discussion HIV T8I 122 125 SP1;SP1;Capsid 118;177;115 121;180;117 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. For example, an L125F substitution in the V1V2 stem created a clash with an aromatic residue in V3 (Phe317) and resulted in an increase in V3 exposure on the Env spike of the JRFL virion. 2018 The Journal of biological chemistry Discussion HIV L125F 16 21 Env 158 161 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Here, we describe the introduction of further, structure-guided modifications to the V3 region of SOSIP.v4.1 and SOSIP.v5.2 trimers, specifically the introduction of two hydrophobic residues, S306L and R308L, within V3. 2018 The Journal of biological chemistry Discussion HIV R308L;S306L 202;192 207;197 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Single substitutions only partially reduced V3 exposure and the introduction of three hydrophobic residues via the S306L, R308L, and A316W changes was necessary for the full effect. 2018 The Journal of biological chemistry Discussion HIV A316W;R308L;S306L 133;122;115 138;127;120 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. This goal was successfully accomplished; the S306L and R308L substitutions reduced V3 mAb binding to the resulting trimers and reduced CD4-induced conformational changes. 2018 The Journal of biological chemistry Discussion HIV R308L;S306L 55;45 60;50 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. This outcome was achieved via the S306L and R308L hydrophobic substitutions, which complement the previously described A316W change. 2018 The Journal of biological chemistry Discussion HIV A316W;R308L;S306L 119;44;34 124;49;39 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. Thus, the S306L and R308L substitutions clearly do affect an immunogenic region of V3 (Table 5). 2018 The Journal of biological chemistry Discussion HIV R308L;S306L 20;10 25;15 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. We have also shown that the immunogenicity of the V3 region in rabbits can be reduced by the introduction of an A316W substitution that helps to lock the V3 region within the body of the trimer and thereby reduces its surface exposure. 2018 The Journal of biological chemistry Discussion HIV A316W 112 117 29222332 Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers. When rabbits were immunized with the BG505 SOSIP.v5.2 S306L/R308L trimer, the induction of V3-targeting tier 1A SF162 NAbs was reduced by 10- and 5-fold compared with SOSIP.664 or SOSIP.v5.2, respectively. 2018 The Journal of biological chemistry Discussion HIV R308L;S306L 60;54 65;59 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. Although an OLA can detect only one mutation at a time, the fragment of HIV pol amplified in this work contains several other high-profile mutations including K103N, Y181C, and V106M. 2018 Analytical biochemistry Discussion HIV K103N;V106M;Y181C 159;177;166 164;182;171 Pol 76 79 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. Cross sectional data suggests that the four mutations M184V, K103N, Y181C, and V106M would identify at least 90% of patients with resistance on a first-line regimen. 2018 Analytical biochemistry Discussion HIV K103N;M184V;V106M;Y181C 61;54;79;68 66;59;84;73 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. The assay detects the presence of the most common HIV-1 drug resistance mutation, M184V, in a paper format following isothermal amplification by RPA. 2018 Analytical biochemistry Discussion HIV M184V 82 87 29229373 Paper-based detection of HIV-1 drug resistance using isothermal amplification and an oligonucleotide ligation assay. This paper describes two key steps that each make drug resistance detection more accessible: (1) isothermal amplification of a region that contains the major mutations that account for resistance to first-line therapies, and (2) lateral flow-based identification of M184V. 2018 Analytical biochemistry Discussion HIV M184V 266 271 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. A natural polymorphism M50I was found in 18% of INSTI-naive patients, which is in-line with the prevalence of this mutation in different subtypes in the Stanford HIV drug resistance database, ranging between 3% to 33% (median 10.5%). 2018 AIDS (London, England) Discussion HIV M50I 23 27 INSTI 48 53 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. A selection of R263K/M50I has been described in virus outgrowth assay for BIC that resulted 2.8-fold reduction of BIC-susceptibility, but M50I alone did not have any effect. 2018 AIDS (London, England) Discussion HIV M50I;M50I;R263K 21;138;15 25;142;20 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. In breakthrough selections, M50I emerges after R263K and provides replication advantage to R263K containing virus. 2018 AIDS (London, England) Discussion HIV M50I;R263K;R263K 28;47;91 32;52;96 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Instead, 17 (6.3%) patients had major INSTI accessory mutations (E157Q, T97A andA128T). 2018 AIDS (London, England) Discussion HIV E157Q;T97A 65;72 70;76 INSTI 38 43 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Mutation R263K mutation has been shown to confer 2- to 5-fold resistance to DTG, with decreased viral replication and strand transfer activity. 2018 AIDS (London, England) Discussion HIV R263K 9 14 29239896 Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. Seven of our 24 recombinant viruses had pre-existing M50I but the EC50 for all INSTIs were very low confirming no effect of this mutation alone ex vivo. 2018 AIDS (London, England) Discussion HIV M50I 53 57 INSTI 79 85 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. Similarly, the cell-surface expression and antiviral activity of the single Asn mutants, N65A and N92A, were not diminished by kifunensine treatment. 2018 Viruses Discussion HIV N65A;N92A 89;98 93;102 29303997 High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release. Tetherin from an owl monkey kidney cell line was shown to not restrict HIV-1 due to the presence of a Thr at residue 181 that prevented efficient glycosylation; mutation of Thr 181 to Ile rescued its glycosylation and antiviral function. 2018 Viruses Discussion HIV T181I 173 187 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Another possible explanation is that the variant with the N155H mutation is more fit than the E138K + Q148K mutant in the presence of raltegravir in this particular setting due to other factors (e.g. 2018 Retrovirology Discussion HIV E138K;N155H;Q148K 94;58;102 99;63;107 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In Pt 1, secondary resistance mutation E138K was detected at baseline (0.1%) and appeared to have acquired Q148K as in the subsequent sample a double mutant with E138K + Q148K was detected (0.5%) which persevered in the population (44.7% in the final sample). 2018 Retrovirology Discussion HIV E138K;E138K;Q148K;Q148K 39;162;107;170 44;167;112;175 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In the final sample (169 days) Y143C was not detected anymore but virus with mutation Y143R completely dominated the viral population. 2018 Retrovirology Discussion HIV Y143C;Y143R 29;86 36;91 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. In the majority of subtype B viruses, the Y143R substitution requires two nucleotide changes (Y143 = TAC TGC = 143C CGC = 143R). 2018 Retrovirology Discussion HIV Y143R 42 47 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Only the major resistance mutation detected before therapy in Pt3, Y143C (0.2% in 2nd sample on day 0), ultimately became the dominant variant in the resistant population although it surprisingly disappeared from the subsequent sample to reappear in the 4th sample (11.8% on day 70). 2018 Retrovirology Discussion HIV Y143C 67 72 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. Remarkably, in Pt1 a variant with major mutation N155H and no apparent secondary resistance mutations emerged after and then co-existed alongside the E138K + Q148K double mutant, each comprising roughly 50% of the viral population. 2018 Retrovirology Discussion HIV E138K;N155H;Q148K 150;49;158 155;54;163 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. So it appears that the Y143C variant detected at baseline facilitated selection of the more resistant Y143R variant in this patient. 2018 Retrovirology Discussion HIV Y143C;Y143R 23;102 28;107 29304821 Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance. This suggests a fitness advantage for the N155H single mutant over the E138K + Q148K double mutant. 2018 Retrovirology Discussion HIV E138K;N155H;Q148K 71;42;79 76;47;84 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. In this respect, more than half of our cohort possessed the G190A mutation associated with different levels of NNRTI resistance (intermediate resistance for efavirenz, potential low level resistance for etravirine, high level resistance for nevirapine, and low level resistance for rilpivirine). 2018 PloS one Discussion HIV G190A 60 65 NNRTI 111 116 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. This subtype is associated with a high prevalence of cross-class primary resistance to NNRTI in our area, with more than half the cases presenting the G190A resistance mutation. 2018 PloS one Discussion HIV G190A 151 156 NNRTI 87 92 29309418 Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naive patients in southern Spain. Unlike the G190A mutation though, the above mentioned polymorphism only confers low-level resistance to NNRTI. 2018 PloS one Discussion HIV G190A 11 16 NNRTI 104 109 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. For enzymes showing higher accuracy such as AMV RT, MLV RT and the mutant HIV-1ESP49 RTs O_K65R and O_K65R/V75I, differences in accuracy cannot be determined in a reliable manner due to the sequence heterogeneity of the RNA used as template. 2018 Scientific reports Discussion HIV K65R;K65R;V75I 91;102;107 95;106;111 RT;RT;RT 48;56;85 50;58;88 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. for O_K65R and O_K65R/V75I RTs), with RNA templates we obtained error rates that were more than three-fold higher with all tested enzymes. 2018 Scientific reports Discussion HIV K65R;K65R;V75I 6;17;22 10;21;26 RT 27 30 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. In our experiments, the large deletions at the 3' end of the primer were found only in the mutational spectra induced by HIV-1BH10, HIV-1ESP49 and the O_K65R RT, but not with oncoretroviral RTs such as MLV or AMV RTs and the HIV-1ESP49 mutant K65R/V75I. 2018 Scientific reports Discussion HIV K65R;K65R;V75I 243;153;248 247;157;252 RT;RT;RT 158;190;213 160;193;216 29330371 Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases. While HIV-1BH10 RT is >15-fold less accurate than HIV-1ESP49 mutant RTs K65R and K65R/V75I in DNA-dependent DNA synthesis reactions, differences between the most and least faithful RTs fall within less than two-fold in assays carried out with RNA templates (Table 1). 2018 Scientific reports Discussion HIV K65R;K65R;V75I 72;81;86 76;85;90 RT;RT;RT 16;68;181 18;71;184 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. Furthermore, the p6*-PR fragments released from different sequences (e.g., wt vs F56C/L63P) also exhibited diverse IDV response profiles (Fig 7D-7F), indicating that precursor autoprocessing could be influenced by different PR sequences leading to liberation of various products We and others previously reported that a p6*-PR fragment resulting from a mutated proximal site can partially process Gag polyprotein, suggesting that these p6*-PR fragments could contribute to Gag processing during virion maturation. 2018 PloS one Discussion HIV F56C;L63P 81;86 85;90 Gag;Gag;Gag;Gag;Gag;PR;PR;PR;PR 397;473;17;320;436;21;224;324;440 400;476;19;322;438;23;226;326;442 29338056 Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors. In this regard, it is interesting to note that F56C/L63P generated more p6*-PRb (Fig 7E) but less mature PR, p6*-PRa, and p6*-PRc than the WT control. 2018 PloS one Discussion HIV F56C;L63P 47;52 51;56 Gag;Gag;Gag;PR 72;109;122;105 74;111;124;107 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. 5d), although the RPA70 loading defect of the Q65R mutant was complemented by TSA. 2018 Retrovirology Discussion HIV Q65R 46 50 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Considering that Cul4 regulates H2B ubiquitination for facilitating the DDR and that the Q65R mutant is ubiquitination-defective due to its inability to bind DDB1/VprBP, it is plausible that H2B is a target of Vpr-mediated ubiquitination, which is critical for Vpr-induced RPA70 loading. 2018 Retrovirology Discussion HIV Q65R 89 93 Vpr;Vpr 210;261 213;264 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Interestingly, the FRAP assay revealed that the recovery of H2B after photo-bleaching was more rapid in cells expressing Vpr-Wt than in those expressing the Q65R mutant. 2018 Retrovirology Discussion HIV Q65R 157 161 Vpr 121 124 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Intriguingly, when the Q65R mutant was forced to accumulate on the LacO repeats, it could not stimulate RPA70 loading. 2018 Retrovirology Discussion HIV Q65R 23 27 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. Moreover, the ubiquitination of H2B was promoted by Vpr-Wt, but not by the Q65R mutant. 2018 Retrovirology Discussion HIV Q65R 75 79 Vpr 52 55 29338752 Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response. This step was demonstrated via experiments using well-characterised Q65R mutant, which is defective in the ubiquitination process. 2018 Retrovirology Discussion HIV Q65R 68 72 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Among the total of 8 amino-acid substitutions introduced in this study (Table 1), Q151M, Y115F, F116Y, and L74V have been reported as mutations associated with NRTI resistance in HIV-1 RT. 2018 Scientific reports Discussion HIV F116Y;L74V;Q151M;Y115F 96;107;82;89 101;111;87;94 NRTI;RT 160;185 164;187 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We also determined the crystal structure of HIV-1 RTQ151M in complex with DNA, DNA:dGTP, and DNA:ETV-TP, which revealed that ETV-TP is bound at the N-site, directly pushing the Met184 side chain. 2018 Scientific reports Discussion HIV Q151M 52 57 RT 50 52 29374261 HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. We generated 5 HIV-1 RT mutants to mimic the HBV RT N-site, constructing recombinant HIV-1 containing those HIV-1 RT mutants for viral replication and anti-viral assays, and found that the Q151M mutation of HIV-1 RT alone is critical for conferring high ETV sensitivity on HIV-1. 2018 Scientific reports Discussion HIV Q151M 189 194 RT;RT;RT;RT 21;49;114;213 23;51;116;215 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. 7B), all three resultant highly DRV-resistant variants (HIV-1DRVRP10, HIV-1DRVRP30, and HIV-1DRVRP51) contained the V32I substitution, and all the HIV-1 infectious clones that were selected with DRV and developed high-level DRV resistance also contained the substitution. 2018 mBio Discussion HIV V32I 116 120 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. As discussed above, in regard to the selection results of rHIVL33F/I84V, which developed high-level DRV resistance without acquiring A71V, the development of high-level DRV resistance in cases of HIV-1DRVRP10, HIV-1DRVRP30, and HIV-1DRVRP51 also involved alternative albeit unidentified pathways in the development of DRV resistance. 2018 mBio Discussion HIV A71V;I84V 133;67 137;71 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Furthermore, A71V compensated for the compromised viral fitness by acquisition of V32I. 2018 mBio Discussion HIV A71V;V32I 13;82 17;86 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Here, we demonstrate that one of the four critical amino acid substitutions responsible for DRV resistance, V32I, serves as a key substitution; it rarely occurs in in vitro selection attempts, but once it occurs, it predisposes HIV-1 to develop high-level DRV resistance. 2018 mBio Discussion HIV V32I 108 112 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. However, when two clones (rHIVV32I and rHIVI54M) were selected, rHIVV32I and rHIVI54M relatively rapidly acquired A71V by 7 weeks of selection and rHIVI54M subsequently acquired V32I as well. 2018 mBio Discussion HIV A71V;V32I 114;178 118;182 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Importantly, the V32I substitution did confer hypersusceptibility to DRV, while the other three substitutions did not significantly change the susceptibility (Table 1). 2018 mBio Discussion HIV V32I 17 21 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In addition, A71V is also known as one of the common polymorphisms found in several percent PI-naive patients. 2018 mBio Discussion HIV A71V 13 17 PI 92 94 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In any event, the data together strongly suggest that the V32I substitution (and the three associated substitutions as a single substitution) is not by itself a DRV resistance-associated mutation, but does facilitate DRV resistance when present. 2018 mBio Discussion HIV V32I 58 62 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In contrast, a set of data compiled for NDA21-976/S003 and NDA21-976/S004 clearly indicates that 10 amino acid substitutions including L10F, V32I, L33F, S37N, M46I, I47V, I50V, L63P, A71V, and I84V are the most prevalent (https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021976s003s004lbl.pdf). 2018 mBio Discussion HIV A71V;I47V;I50V;I84V;L10F;L33F;L63P;M46I;S37N;V32I 183;165;171;193;135;147;177;159;153;141 187;169;175;197;139;151;181;163;157;145 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In fact, the presence of the V32I substitution has been significantly associated with treatment failure in those receiving DRV-containing regimens. 2018 mBio Discussion HIV V32I 29 33 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In particular, considering that the V32I substitution is seen in some HIV-1 variants resistant to other PIs than DRV, the V32I substitution is not necessarily specific to DRV resistance but likely associated with pan-PI resistance as well. 2018 mBio Discussion HIV V32I;V32I 36;122 40;126 PI;PI 104;217 107;219 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In the present study, at least four amino acid substitutions, V32I, I54M, A71V, and I84V, obviously facilitate a high level of DRV resistance. 2018 mBio Discussion HIV A71V;I54M;I84V;V32I 74;68;84;62 78;72;88;66 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In the present study, we concluded that the V32I substitution serves as a key substitution, which rarely occurs in the presence of DRV without other DRV resistance-predisposing amino acid substitutions, but once it occurs, it significantly predisposes HIV-1 to develop high-level DRV resistance. 2018 mBio Discussion HIV V32I 44 48 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. In this regard, we have expressed and purified several mutated proteases associated with DRV resistance such as that from highly DRV-resistant HIV-1DRVRP51 that contains various amino acid substitutions including V32I, L33F, I54M, and I84V, generated crystals of such proteases complexed with DRV and other PIs, and are analyzing the crystallographic structures of those complexes, which should give more in-depth insights in the understanding of the mechanism of the high genetic barrier of DRV. 2018 mBio Discussion HIV I54M;I84V;L33F;V32I 225;235;219;213 229;239;223;217 PR;PR;PI 63;268;307 72;277;310 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It is interesting that when rHIVL33F/I84V was selected, this clone continued to propagate in the presence of increasing concentrations of DRV, acquired V32I (as examined at week 26) but without acquiring A71V, and became capable of propagating in the presence of 1 microM DRV by 26 weeks of selection. 2018 mBio Discussion HIV A71V;I84V;V32I 204;37;152 208;41;156 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It is noteworthy that the key amino acid substitutions focused on in the present study, including not only V32I but also L33F, I54M, and I84V, as a single substitution do not by themselves confer resistance to DRV. 2018 mBio Discussion HIV I54M;I84V;L33F;V32I 127;137;121;107 131;141;125;111 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It is noteworthy that V32I was reportedly involved in the development of pan-PI resistance including DRV resistance as estimated by an independent correlation network analysis of amino acid substitutions identified in HIV-1 proteases studied from more than 10,000 patients receiving PI-containing regimens. 2018 mBio Discussion HIV V32I 22 26 PR;PI;PI 224;77;283 233;79;285 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. It should be noted that all the highly DRV-resistant HIV-1 variants (HIV-1DRVRP10, HIV-1DRVRP30, and HIV-1DRVRP51) did not contain the A71V substitution as the PR-encoding gene of those variants were directly sequenced, although when a highly drug-resistant clinical HIV-1 isolate, HIVc, was selected with DRV, that isolate eventually acquired A71V by passage 50. 2018 mBio Discussion HIV A71V;A71V 135;344 139;348 PR 160 162 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. Nevertheless, no detailed analysis on the role of A71V in the development of DRV resistance has been reported. 2018 mBio Discussion HIV A71V 50 54 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. reported that 11 amino acid substitutions, V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V, and L89V, which appear to be associated with HIV-1 resistance against DRV, were identified among HIV-1 variants isolated from patients treated with DRV-including regimens on POWER studies. 2018 mBio Discussion HIV G73S;I47V;I50V;I54L;I54M;I84V;L33F;L76V;L89V;V11I;V32I 81;61;67;73;73;93;55;87;103;43;49 85;65;71;79;79;97;59;91;107;47;53 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. reported that the V32I substitution was seen in 24% of clinical HIV-1 isolates from 54 multiple-PI-experienced but non-DRV-exposed HIV-1-infected individuals, but the prevalence of the substitution increased to 57% in those who subsequently received DRV-containing regimens and underwent treatment failure with such regimens. 2018 mBio Discussion HIV V32I 18 22 PI 96 98 HIV infections 131 145 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. rHIVL33F/I84V's acquisition of high-level DRV resistance despite the absence of A71V strongly suggested that its DRV resistance acquisition involved an alternate albeit unidentified pathway of DRV resistance development. 2018 mBio Discussion HIV A71V;I84V 80;9 84;13 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. showed that the V32I substitution was present in 64% of HIV-1 isolates from 25 DRV-naive patients after treatment failure. 2018 mBio Discussion HIV V32I 16 20 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The A71V substitution has been seen in 20.4, 20.1, and 6.2% of nelfinavir-, lopinavir (LPV)-, and atazanavir-experienced patients, respectively, compared to 3.5 to 5.4% of HIV-1 isolates from PI-naive patients. 2018 mBio Discussion HIV A71V 4 8 PI 192 194 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The A71V substitution is relatively frequently seen as a secondary mutation in clinically isolated HIV-1 variants resistant to FDA-approved PIs. 2018 mBio Discussion HIV A71V 4 8 PI 140 143 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The A71V substitution likely changes the configuration of the A71-containing beta-sheet and the hydrogen bond network propagating to the binding pocket, changing the shape of the "ligand binding tunnel," and affecting the interactions, in which the catalytic site amino acid residues (Asp25 and Asp25') are involved. 2018 mBio Discussion HIV A71V 4 8 Asp;Asp 285;295 288;298 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The detailed structural analysis of the major amino acid substitutions conferring high-level DRV resistance on HIV-1 including V32I, L33F, I54M, and I84V remains to be conducted. 2018 mBio Discussion HIV I54M;I84V;L33F;V32I 139;149;133;127 143;153;137;131 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The present data not only explain well the mechanisms of DRV's high genetic barrier but also suggest that the initiation or continuation of DRV-containing regimens in individuals harboring HIV-1 variants with V32I substitution must be carefully considered and monitored. 2018 mBio Discussion HIV V32I 209 213 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. The reason why the three clones (rHIVWT, rHIVL33F, and rHIVM46I) failed to develop DRV resistance is unknown at this time, although it is possible that the acquisition of A71V, a secondary substitution observed among HIV-1 isolates resistant to various PIs, might render each clone more susceptible to DRV and/or compromise their replication fitness, and A71V substitution rarely emerged. 2018 mBio Discussion HIV A71V;A71V 171;355 175;359 PI 253 256 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These data suggest that the V32I substitution is strongly associated with the development of DRV resistance. 2018 mBio Discussion HIV V32I 28 32 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These four mutations are commonly seen as PI-associated amino acid substitutions, and V32I (3.9%), I54M (1.3%), and I84V (14.5%) were actually found in 1,021 genotypes from patients who failed in regimens including PIs other than DRV. 2018 mBio Discussion HIV I54M;I84V;V32I 99;116;86 103;120;90 PI;PI 42;215 44;218 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. These structural insights can help explain why the IC50 of rHIVV32I/A71V is comparable to that of rHIVWT (Table 2), while rHIVV32I/I54M and rHIVV32I/I84V were still highly sensitive to DRV (Table 2). 2018 mBio Discussion HIV A71V;I54M;I84V 68;131;149 72;135;153 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. This study showed that V32I and I84V substitutions in protease played a significant role, but there was no mention of A71V. 2018 mBio Discussion HIV A71V;I84V;V32I 118;32;23 122;36;27 PR 54 62 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. When rHIVA71V was selected, this clone acquired V32I and other amino acid substitutions and became capable of propagating in the presence of 1 microM DRV by 25 weeks of selection. 2018 mBio Discussion HIV V32I 48 52 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. When rHIVI84V was selected, this clone quickly acquired A71V by 8 weeks of selection, subsequently acquired V32I by 17 weeks of selection, and was replicating in the presence of 1 microM DRV by 29 weeks of selection. 2018 mBio Discussion HIV A71V;V32I 56;108 60;112 29511083 Mechanism of Darunavir (DRV)'s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance. When rHIVV32I/I54M was selected, this clone acquired A71V more quickly by 5 weeks of selection and became capable of replicating in the presence of 1 microM DRV by 22 weeks of selection. 2018 mBio Discussion HIV A71V;I54M 53;14 57;18 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Additionally, of 69 samples with >= 2.5-fold decrease in susceptibility to RPV, 44 (64%) had K103N. 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N 93 98 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. In a small study of three patients who had HIV-1 with K103N from prior NNRTI-containing therapy with no other NNRTI mutations, all three responded well to a switch from boosted protease inhibitor-based second-line therapies to RPV/tenofovir/emtricitabine. 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N 54 59 PR;NNRTI;NNRTI 177;71;110 185;76;115 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. In our study, K103N was found in 55 of 100 samples collected from an ART-experienced study population. 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N 14 19 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. In the ECHO and THRIVE trials, pre-existing K103N alone did not reduce RPV susceptibility in participants who added RPV to an existing NRTI-based ART regimen. 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N 44 49 NRTI 135 139 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. Other studies have reported an association of RPV resistance with K103N combined with other NNRTI resistance mutations, especially L100I, in clinical samples. 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N;L100I 66;131 71;136 NNRTI 92 97 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. The clinical implications of the interactions between K103N and NNRTI mutations in conferring RPV resistance is unknown, and should be monitored as the use of RPV expands for both treatment and prevention. 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N 54 59 NNRTI 64 69 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. The decrease in susceptibility was due to the additive effect of K103N with other RPV-associated NNRTI resistance mutations (Figure 2). 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N 65 70 NNRTI 97 102 29566538 Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa. The most frequently transmitted NNRTI mutation is K103N, but relatively little is known clinically about cross-resistance of K103N to RPV. 2018 Antiviral chemistry & chemotherapy Discussion HIV K103N;K103N 50;125 55;130 NNRTI 32 37 29584723 Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort. High-frequency mutations transmitted from ARV-naive partners likely represent transmission chains of drug-resistant variants, whereas there are alternate explanations for the presence of the G73S accessory mutation as minority variants in both transmitters and recipients. 2018 PLoS medicine Discussion HIV G73S 191 195 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Although the pattern is the same between cell types, the greater impact of the E300R mutation on virus replication in Jurkat and CD4+ T cells than in TZM-bl cells may result from a cell type difference, as WT virus replication was weak compared to that in Jurkat and CD4+ T cells. 2018 mBio Discussion HIV E300R 79 84 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Furthermore, hydrogen bonding frequency analysis of the RTp66 mutants showed that the R298 side chain (E298R mutant) forms a salt bridge with the E297 side chain and that the R300 side chain (E300R mutant) has an increased frequency of salt bridge interactions with the E248 and D250 side chains. 2018 mBio Discussion HIV E298R;E300R 103;192 109;198 RT 56 58 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. However, HIV-1 with the E298R mutation in RT uncoated faster than the E300R RT mutant virus, despite having more substantial impairment of in vitro RT activity and reverse transcription completion in cells. 2018 mBio Discussion HIV E298R;E300R 24;70 29;75 RT;RT;RT;RT 164;42;76;148 185;44;78;150 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. However, the E300R mutant RT heterodimer had a greater rate of dissociation from eEF1A than the WT, suggesting that the E300R mutant RT heterodimer complexed with eEF1A is less stable. 2018 mBio Discussion HIV E300R;E300R 13;120 18;125 RT;RT 26;133 28;135 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Molecular dynamic simulations revealed that the W252A, L303A, and E298R mutations caused similar widespread structural changes and also caused a major redistribution across the surface of the thumb domain, including the acidic patch of residues. 2018 mBio Discussion HIV E298R;L303A;W252A 66;55;48 71;60;53 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Optimal uncoating kinetics within 1 h of infection are tightly linked with HIV-1 infectivity, which may be why E300R mutant HIV-1 is less infective than E298R mutant HIV-1. 2018 mBio Discussion HIV E298R;E300R 153;111 158;116 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Our data do not disagree with this but suggest that the larger negative impact of E300R mutant RT on uncoating kinetics was a result of more impaired interaction with eEF1A. 2018 mBio Discussion HIV E300R 82 87 RT 95 97 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Previously, we showed that eEF1A can interact with the RTp51 subunit, the RTp66 subunit, and the heterodimer individually, and here we used cotransfected WT or E300R mutant RTp51 and RTp66 in a co-IP experiment that indicated that eEF1A can bind WT RTp51 or RTp66 in a heterodimer. 2018 mBio Discussion HIV E300R 160 165 RT;RT;RT;RT;RT;RT 55;74;173;183;249;258 57;76;175;185;251;260 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Purified WT and E300R mutant RT heterodimer had the same in vitro RT catalytic activity, but E300R mutant RT had lower eEF1A binding affinity. 2018 mBio Discussion HIV E300R;E300R 16;93 21;98 RT;RT;RT 29;66;106 31;68;108 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Reverse transcription first strand transfer can only occur when HIV-1 RNase H can degrade the RNA complement to the ssDNA, indicating that RNase H activity was not affected by the E300R mutation since first strand transfer efficiency was similar to that of WT HIV-1. 2018 mBio Discussion HIV E300R 180 185 RT 0 21 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The binding affinity of the purified WT RT heterodimer for eEF1A was similar to that in a previous report, and the weaker eEF1A binding affinity of the E300R mutant RT heterodimer supports the co-IP and NanoBRET data. 2018 mBio Discussion HIV E300R 152 157 RT;RT 40;165 42;167 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The clearest example of this is the E300R mutant RT, which has no change in in vitro catalytic activity but a significant reduction in the interaction with eEF1A and significantly impaired HIV-1 reverse transcription kinetics and efficiency. 2018 mBio Discussion HIV E300R 36 41 RT;RT 195;49 216;51 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The CsA washout assay showed that the E298R and E300R HIV-1 mutants both had delayed uncoating kinetics compared to those of WT and E297R mutant HIV-1. 2018 mBio Discussion HIV E297R;E298R;E300R 132;38;48 137;43;53 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E297R, E298R, and E300R mutations showed weak, moderate, and strong reductions in the RT-eEF1A interaction, respectively, while causing mild, moderate, and no impairment of the predicted RT structural stability, respectively. 2018 mBio Discussion HIV E297R;E298R;E300R 4;11;22 9;16;27 RT;RT 90;191 92;193 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E297R, E298R, and E300R mutations, representing various levels of RT-eEF1A interaction impairment and predicted effect on structural stability, were introduced into HIV-1 proviral DNA for further investigation. 2018 mBio Discussion HIV E297R;E298R;E300R 4;11;22 9;16;27 RT 70 72 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E300R mutation is the only currently identified mutation of a strictly conserved and surface-exposed HIV-1 RT residue that reduces interaction with eEF1A without affecting RT protein stability or in vitro RT catalytic activity and provides a useful tool for investigating the role of the RT-eEF1A interaction in HIV-1 replication. 2018 mBio Discussion HIV E300R 4 9 RT;RT;RT;RT 111;176;209;292 113;178;211;294 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The E300R mutation, which had the most defective binding compared to the other mutations in co-IP and NanoBRET assays, had a similar in vitro rate of association with eEF1A in the BLI assay. 2018 mBio Discussion HIV E300R 4 9 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The predicted moderate instability of RT harboring an E298R mutation resulted in a significant 60% reduction in RT catalytic activity in vitro, highlighting the importance of the E298 amino acid residue in RT enzyme structure and function. 2018 mBio Discussion HIV E298R 54 59 RT;RT;RT 38;112;206 40;114;208 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The reduced efficiency of first strand transfer in HIV-1 with the E298R mutation indicates a partially defective RT enzyme compared to WT, E297R mutant, and E300R mutant HIV-1, which had competent first strand transfer, supporting the in vitro RT catalytic activity assay results. 2018 mBio Discussion HIV E297R;E298R;E300R 139;66;157 144;71;162 RT;RT 113;244 115;246 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. The reduced efficiency of reverse transcription in E298R and E300R mutant HIV-1, measured by the percentage of late DNA copies compared to first strand transfer DNA copies, matches the known characteristic of HIV-1 with reduced RT interaction with eEF1A during infection. 2018 mBio Discussion HIV E298R;E300R 51;61 56;66 RT;RT 26;228 47;230 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Therefore, it is unlikely that the uncoating and replication phenotypes of E300R mutant HIV-1 are from changes in the functionality of RT, since the known substantial effect of the E298R mutation on RT functionality affects these processes less than the E300R mutation. 2018 mBio Discussion HIV E298R;E300R;E300R 181;75;254 186;80;259 RT;RT 135;199 137;201 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Therefore, the significantly reduced infectivity and replication of HIV-1 harboring the E300R mutation can be attributed to the defective and delayed reverse transcription and uncoating as a result of reduced interaction with eEF1A. 2018 mBio Discussion HIV E300R 88 93 RT 150 171 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Therefore, these side chains in the E298R and E300R mutants would likely be less available for hydrogen bonding with eEF1A if these residues in WT RT do interact with eEF1A through salt bridge interactions. 2018 mBio Discussion HIV E298R;E300R 36;46 41;51 RT 147 149 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. This is in contrast to the E298R mutation, which is predicted to affect overall RT structural stability and inhibits in vitro enzymatic activity and RNase H activity. 2018 mBio Discussion HIV E298R 27 32 RT 80 82 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. This raises the possibility that the larger structure-destabilizing effect of E298 may reduce the RT-eEF1A interaction by a mechanism similar to that of the W252A and L303A mutations described previously, and this mutation thereby acts via a mechanism different from that of the E300R mutation. 2018 mBio Discussion HIV E300R;L303A;W252A 279;167;157 284;172;162 RT 98 100 29588400 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. Unexpectedly, the mild increase in predicted structural instability of the E297R mutation in RT did not reduce RT catalytic activity and instead significantly increased RT catalytic activity by 50% in vitro. 2018 mBio Discussion HIV E297R 75 80 RT;RT;RT 93;111;169 95;113;171 29595649 Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. Interestingly, a vertically transmitted minority DRM (K103N), known to be associated with resistance to NNRTIs used both for PMTCT and first-line HAART in SSA, was found in a PMTCT-exposed infant, thus suggesting NNRTI-sparing regimens for such children. 2018 Medicine Discussion HIV K103N 54 59 NNRTI;NNRTI 104;213 110;218 29595649 Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children. NNRTI mutations (E138A and V179D), found in children without PMTCT-exposure, are known as polymorphisms with little or no effect on drug susceptibility or virological response. 2018 Medicine Discussion HIV E138A;V179D 17;27 23;32 NNRTI 0 5 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. Analyses in this study suggest that individuals on PI-based regimens are at elevated risk for CSF escape, and that risk may extend to individuals with historic M184V/I mutations and CSF accumulation of major DRMs. 2018 Clinical infectious diseases Discussion HIV M184I;M184V 160;160 167;167 PI 51 53 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. However, when resistance mutations were factored into CPE values among participants with common NRTI M184V/I mutations, median adjusted CPE scores in CSF were low, suggesting that accumulation of resistance mutations in the CNS may lead to ineffective viral control despite regimens with high unadjusted CPE values. 2018 Clinical infectious diseases Discussion HIV M184I;M184V 101;101 108;108 NRTI 96 100 29617912 Impact of Antiretroviral Regimens on Cerebrospinal Fluid Viral Escape in a Prospective Multicohort Study of Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-1-Infected Adults in the United States. These analyses also show that CSF escape cases with M184V/I are likely to harbor variants with major DRMs that confer resistance to at least 1 ART drug. 2018 Clinical infectious diseases Discussion HIV M184I;M184V 52;52 59;59 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. (2012) compared structural and biochemical features of PR1 (PDB code: 2IEN), PR2 (PDB code: 3EBZ), and PR1 mutant with three substitutions (V32I, I47V, and V82I PDB code: 3S43) complexed with DRV. 2018 Scientific reports Discussion HIV I47V;V32I;V82I 146;140;156 150;144;160 PR;PR;PR 77;55;103 80;58;106 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. (2016) who showed that the four substitutions I32V, V47I, M76L, and I82V in PR2 cooperate to confer a level of PI susceptibility greater than the sum of each change individually. 2018 Scientific reports Discussion HIV I32V;I82V;M76L;V47I 46;68;58;52 50;72;62;56 PR;PI 76;111 79;113 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. As a perspective, this step could be performed using directed mutagenesis and crystallographic analysis of the recombinant protein obtained with the L76M mutation. 2018 Scientific reports Discussion HIV L76M 149 153 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Differences in interaction network was previously observed for SQV in PR1 and PR1 mutant with three substitutions I32V, V47I, and I82V: in PR1 mutant complex, SQV established more contact with PR1 mutant than with PR1. 2018 Scientific reports Discussion HIV I32V;I82V;V47I 114;130;120 118;134;124 PR;PR;PR;PR;PR 70;78;139;193;214 73;81;142;196;217 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. For example, the comparison of the crystallographic structures of PR1 and PR2 complexed with DRV showed that hydrophobic interactions between DRV and PR2 are more elongated than those in PR1-DRV complex and supposed to result from substitutions V32I, I47V, and V82I. 2018 Scientific reports Discussion HIV I47V;V32I;V82I 251;245;261 255;249;265 PR;PR;PR;PR 74;150;66;187 77;153;69;190 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. In addition, mutations V32I and L76M induce structural change at residue 45. 2018 Scientific reports Discussion HIV L76M;V32I 32;23 36;27 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. In addition, the putative role of the substitutions V32I, I47V, and V82I in the alteration of PI interactions with residues 32, 47, and 82 have been previously reported in several studies. 2018 Scientific reports Discussion HIV I47V;V32I;V82I 58;52;68 62;56;72 PI 94 96 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. It would be interesting to validate the putative role of the substitution L76M in the structural deformation of residue 45_B between PR1 and PR2 structures. 2018 Scientific reports Discussion HIV L76M 74 78 PR;PR 141;133 144;136 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Therefore, our results suggest that the T31S, M46I, and V82I amino acid changes induce structural changes in PR2 that can affect PI binding. 2018 Scientific reports Discussion HIV M46I;T31S;V82I 46;40;56 50;44;60 PR;PI 109;129 112;131 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. This interaction between APV and residue 47 was re-established in the modelled PR2 mutant containing four substitutions I32V, V47I, M76L, and I82V. 2018 Scientific reports Discussion HIV I32V;I82V;M76L;V47I 120;142;132;126 124;146;136;130 PR 79 82 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. This is consistent with our results that showed that substitution V82I induced that atom 82_A/B_CD1 is absent in PR1 pockets. 2018 Scientific reports Discussion HIV V82I 66 70 PR 113 116 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Thus, to validate the putative role of the substitution L76M, the 3D structure of this mutant should be solved. 2018 Scientific reports Discussion HIV L76M 56 60 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. To do so, the comparison of 45_B residue conformations between crystallographic structures of PR1L76M mutant and wild-type PR1 and PR2 would provide information on the involvement of the substitution L76M in the 45_B residue deformation. 2018 Scientific reports Discussion HIV L76M 200 204 PR;PR;PR 131;94;123 134;97;126 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. Using structural comparisons of single and double PR1 mutants:i.e., L76M or V32I + L76M mutants:we suggested that cooperation between substitutions V32I and L76M induces the structural changes at residue 45 in PR2. 2018 Scientific reports Discussion HIV L76M;L76M;L76M;V32I;V32I 68;83;157;76;148 72;87;161;80;152 PR;PR 210;50 213;53 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. We demonstrated that the property changes between PR1 and PR2 structures are directly explained by the six substitutions (T31S, V32I, M46I, I47V, L76M, and V82I) located in PR pocket. 2018 Scientific reports Discussion HIV I47V;L76M;M46I;T31S;V32I;V82I 140;146;134;122;128;156 144;150;138;126;132;160 PR;PR;PR 58;50;173 61;53;175 29636521 Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases. We showed that PR2 pockets are more hydrophobic than PR1 pockets that it is induced by the substitutions V32I, M46I, and V82I. 2018 Scientific reports Discussion HIV M46I;V32I;V82I 111;105;121 115;109;125 PR;PR 15;53 18;56 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. However, the infectivity defect conferred by the E45A CA mutation appears complex and may be unrelated to the increased core stability. 2018 Cell host & microbe Discussion HIV E45A 49 53 Capsid 54 56 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Importantly, consistent with the nuclear penetration distances of the viral DNA for WT and N74D CA, the N74D mutant complexes failed to undergo significant transport into the nucleoplasm after uncoating at the NE. 2018 Cell host & microbe Discussion HIV N74D;N74D 91;104 95;108 Capsid 96 98 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. On the other hand, disfavored stable docking and nuclear import of hyper-stable E45A HIV-1 cores. 2018 Cell host & microbe Discussion HIV E45A 80 84 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. Our live cell imaging experiments revealed the requirement for nuclear pore-associated uncoating of N74D complexes. 2018 Cell host & microbe Discussion HIV N74D 100 104 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. The delayed completion of uncoating of docked N74D mutant cores at the NE compared to WT cores. 2018 Cell host & microbe Discussion HIV N74D 46 50 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. The use of an alternative nuclear import pathway by the N74D CA mutant has been shown to alter the HIV-1 integration sites. 2018 Cell host & microbe Discussion HIV N74D 56 60 Capsid 61 63 29649444 Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport. This result suggests that the difference in the integration site preference for the N74D and WT CA might be determined by the CA/host factor-dependent nuclear penetration of PICs. 2018 Cell host & microbe Discussion HIV N74D 84 88 Capsid;Capsid 96;126 98;128 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. A secondary analysis of the EARNEST Trial found a much higher prevalence of Q151M amongst subtype-C patients failing first-line ART (11% vs negligible for other non-B subtypes). 2018 AIDS research and therapy Discussion HIV Q151M 76 81 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. As for the Q151M, we should note that improved outcomes may be possible using modern ART regimens. 2018 AIDS research and therapy Discussion HIV Q151M 11 16 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. found a prevalence for Q151M of 4.6% in a review of 1825 patients failing D4T-containing first-line ART drawn largely from LMICs, considerably higher than the peak prevalence observed in the UK. 2018 AIDS research and therapy Discussion HIV Q151M 23 28 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. In combination, these results are consistent with the Q151M mutation possibly being associated with the risk of death, but there is once again the caveat that the link could disappear with more modern ART regimens. 2018 AIDS research and therapy Discussion HIV Q151M 54 59 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. In the period 2010-2014 the prevalence of Q151M in treatment-experienced patients undergoing viral sequencing stabilised at around 0.1% in the UK cohort, equating to an average of four cases per year, whilst the prevalence of T69i was even lower in this period at 0.04% (an average of 1.5 patients per year). 2018 AIDS research and therapy Discussion HIV Q151M 42 47 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. Marked declines in prevalence were observed for both Q151M and T69i in the period 2003-2006, but even in the years before this these mutations were relatively rare amongst patients failing ART (1.5-1.7% for Q151M and 0.4-1.3% for T69i) and Q151M was even rarer in ART-naive patients (0-0.5%) whilst T69i was not observed. 2018 AIDS research and therapy Discussion HIV Q151M;Q151M;Q151M 53;207;240 58;212;245 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. reported an overall prevalence up to February 2010 of 0.8 and 0.5% for Q151M and T69i, respectively. 2018 AIDS research and therapy Discussion HIV Q151M 71 76 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. The very high level of complexity of treatment histories for HIV hampers epidemiological investigation of risk factors for the occurrence of specific resistance mutations, particularly for the analysis of rare mutations such as Q151M and T69i. 2018 AIDS research and therapy Discussion HIV Q151M 228 233 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. We did not find evidence that presence of the Q151M mutation is associated with increased risk of mortality relative to comparable patients matched on ART initiation and resistance testing dates, but it is not possible to draw strong conclusions from the limited data available. 2018 AIDS research and therapy Discussion HIV Q151M 46 51 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. We found strong associations between D4T exposure and emergence of the Q151M mutation, a link previously identified by Nouhin et al. 2018 AIDS research and therapy Discussion HIV Q151M 71 76 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. We have found that the prevalence of multi-drug resistance mutations Q151M and T69i has declined to almost zero in the UK and, as such, it is likely that observation of these mutations will now be very rare in any high-income country. 2018 AIDS research and therapy Discussion HIV Q151M 69 74 29661246 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data. We observed that rbPI use showed both a strong negative association with the emergence of the Q151M mutation and a strong association with viral suppression following detection of the mutation, suggesting that this may be a particularly effective treatment option for affected patients. 2018 AIDS research and therapy Discussion HIV Q151M 94 99 29683855 A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. M184V was detected pretreatment by deep sequencing (Illumina MiSeq) as a minority variant (9.4%). 2018 AIDS (London, England) Discussion HIV M184V 0 5 29683855 A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. Only one patient (D/C/F/TAF) was found to have M184I/V, conferring resistance to emtricitabine; this patient also had a transmitted K103N mutation at screening. 2018 AIDS (London, England) Discussion HIV K103N;M184I;M184V 132;47;47 137;54;54 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. (2017) observed significantly less clustering of mutations T69D and M46I detected in the two sequences within large Slovenian clusters, which indicates that these two mutations are less fit to transmit than the wild type. 2018 PloS one Discussion HIV M46I;T69D 68;59 72;63 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. Equally fit are K103N, K103S, and Y181C mutations, which were detected in four individuals from Slovenia. 2018 PloS one Discussion HIV K103N;K103S;Y181C 16;23;34 21;28;39 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. In contrast to T215Y/F, T215 revertants show no reduction in transmission fitness. 2018 PloS one Discussion HIV T215F;T215Y 15;15 22;22 29698470 HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update. The T215 revertants appear in the absence of drug pressure from T215Y/F mutations that were initially selected under zidovudine treatment. 2018 PloS one Discussion HIV T215F;T215Y 64;64 71;71 29732898 Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States. Notably, the presence of major NNRTI resistance WHO-defined DRM declined significantly from 2007 to 2009, while the prevalence of specific key NNRTI mutations such as K103N and Y181I/C/V also declined in 2009 compared with the preceding years. 2018 AIDS research and human retroviruses Discussion HIV K103N;Y181C;Y181I;Y181V 167;177;177;177 172;186;186;186 NNRTI;NNRTI 31;143 36;148 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. Even considering the previous report of occurrence in Hebei and Beijing, the mutation rate of V179D/T up to 6.92% is still an astonishing level. 2018 BMC infectious diseases Discussion HIV V179D;V179T 94;94 101;101 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. Furthermore, M184 V is the most frequently detected NRTI resistance mutation, which was also found in previous studies. 2018 BMC infectious diseases Discussion HIV M184V 13 19 NRTI 52 56 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. L33F and V179D/T are the types of mutation that confer potential low-level resistance. 2018 BMC infectious diseases Discussion HIV V179D;V179T;L33F 9;9;0 16;16;4 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. One type of PI mutations (L33F), six types of NRTI mutations and seven types of NNRTI mutations have been identified in this population. 2018 BMC infectious diseases Discussion HIV L33F 26 30 NNRTI;NRTI;PI 80;46;12 85;50;14 29739342 High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China. The major TDRMs observed in this study have been reported in a previous study of HIV Drug Resistance among ART-failure individuals in Yunnan Province, which figured out mutations such as M184 V/I, K103 N, V106A, Y181C and G190A were common. 2018 BMC infectious diseases Discussion HIV G190A;K103N;M184I;M184V;V106A;Y181C 222;197;187;187;205;212 227;203;195;195;210;217 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. Taken together, although it is unclear whether N462 or G460a is related to later neutralization breadth development, G460a but not N462 appeared more common in macaques with breadth than those without. 2018 Viruses Discussion HIV G460A;G460A 55;117 60;122 29772652 Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. We further mapped in gp120 V5 two mutations, N462S and G460aE, largely responsible for wave 1 neutralization escape in GB40 and FF69, respectively. 2018 Viruses Discussion HIV N462S 45 50 gp120 21 26 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Accordingly, we observed retention of Tat S46E mutant in the cytoplasm. 2018 Retrovirology Discussion HIV S46E 42 46 Tat 38 41 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. However, we did not detect any strong effect of Tat Ser-16 mutations and only a weak effect of Tat S46D mutation on ubiquitination suggesting that Tat phosphorylation has no direct effect on Tat ubiquitination. 2018 Retrovirology Discussion HIV S46D 99 103 Tat;Tat;Tat;Tat 48;95;147;191 51;98;150;194 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. However, we were able to assemble a recombinant virus with Tat S46E mutation but it replicated poorly comparing to the WT Tat and Tat S16E viruses suggesting that Ser-46 phosphorylation can suppress viral replication. 2018 Retrovirology Discussion HIV S16E;S46E 134;63 138;67 Tat;Tat;Tat 59;122;130 62;125;133 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. In contrast, Tat S46A mutation was clearly inhibitory and Tat S46E mutation did not recover HIV-1 transcription. 2018 Retrovirology Discussion HIV S46A;S46E 17;62 21;66 Tat;Tat 13;58 16;61 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Large scale flexibility analysis of CDK9/cyclin T1/Tat complex showed that in S16P&S46P Tat, flexible domains (residues 18-25 and 29-37) were rotated along the Gln17 residue acting as a hinge by more than 30 resulting in a large shift of the Zn2+ ions. 2018 Retrovirology Discussion HIV S16P;S46P 78;83 82;87 Tat;Tat 51;88 54;91 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Our analysis of Tat binding to cyclin T1 showed that both Ser-16 and Ser-46 aspartic acid mutations reduced the binding. 2018 Retrovirology Discussion HIV S46D 69 89 Tat 16 19 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. The overall Tat phosphorylation was significantly reduced not only with Ser-16 mutation but also with Ser-46 alanine mutation. 2018 Retrovirology Discussion HIV S46A 102 116 Tat 12 15 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. This is in agreement with our findings here that depicted a minimal effect of Tat S46D mutation on the binding to TAR RNA which was only strongly affected by Tat S16A mutation. 2018 Retrovirology Discussion HIV S16A;S46D 162;82 166;86 Tat;Tat 78;158 81;161 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. This rotation was not seen in the S16&S46 complex or S16&S46P complexes. 2018 Retrovirology Discussion HIV S46P 57 61 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Thus, the modeling data indicate that phosphorylated Ser-16 might stabilize CDK9/cyclin T1/Tat complex, while an alanine mutation of Ser-16 destabilized the CDK9/cyclin T1 interface. 2018 Retrovirology Discussion HIV S16A 113 139 Tat 91 94 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. We showed here that HIV-1 transcription was inhibited when Ser-16 residue was mutated to alanine, but the transcription was almost fully recovered with Tat S16E mutation. 2018 Retrovirology Discussion HIV S16E 156 160 Tat 152 155 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. While in their study binding of Tat to TAR RNA was reduced with 23-40-46-62-68 D mutations, single Tat S46D mutation had less pronounced effect on the binding of Tat to TAR RNA. 2018 Retrovirology Discussion HIV S46D 103 107 Tat;Tat;Tat 32;99;162 35;102;165 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. While strong reduction of the binding for aspartic acid mutants was unexpected, the Tat S16E mutant is likely to retain some activity as it is able to replicate. 2018 Retrovirology Discussion HIV S16E 88 92 Tat 84 87 29792216 HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. Yong-Soo Bae and colleagues showed that HIV-1 provirus with S46A mutation was defective in viral replication, providing a support to our current observations that pNL4-3 proviruses with Tat S16A or Tat S46A mutations were inactive. 2018 Retrovirology Discussion HIV S16A;S46A;S46A 190;60;202 194;64;206 Tat;Tat 186;198 189;201 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. 4 included patient 98_co (HIV/HBV) with resistance codon E138A; patient 100_co (HIV/HBV) with codons L10A and L10V; and patient 105_co (HIV/HBV) with codon K103E. 2018 Scientific reports Discussion HIV L10A;L10V 101;110 105;114 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. Additionally, the patient had the L10V, M41L and T215E resistance codons. 2018 Scientific reports Discussion HIV L10V;M41L 34;40 38;44 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. Although the mutation L10V is an accessory mutation to PI, the mutations M41L and T215E are associated with resistance to NNRTI, and are therefore associated with cross resistance. 2018 Scientific reports Discussion HIV L10V;M41L 22;73 26;77 NNRTI;PI 122;55 127;57 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. Codon mutations K219Q, T69N, and K70R generate conditions where the drug AZT has decreased effectiveness. 2018 Scientific reports Discussion HIV K70R 33 37 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. In this study, this mutation was observed 32.3% of the time, and all patients with mutations were using 3TC, supporting the premise that the presence of M184V is due to the selective pressure of 3TC. 2018 Scientific reports Discussion HIV M184V 153 158 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. Patient 91_co (HIV/HCV) has the codons T12S, L19I, L74V, K103R, E122K, D123E, I135T, S163C, M184V, L214F, K219E, E224K, V245M, L100I, V106I, V179D and M230L and used the drugs 3TC, EFV and TDF for treatment. 2018 Scientific reports Discussion HIV L100I;L19I;L214F;L74V;M184V;S163C 127;45;99;51;92;85 132;49;104;55;97;90 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The codon L74I is selected for by ABC. 2018 Scientific reports Discussion HIV L74I 10 14 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The L214F mutation was the most frequent. 2018 Scientific reports Discussion HIV L214F 4 9 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The M41L mutation causes high cross resistance to the drug ABC. 2018 Scientific reports Discussion HIV M41L 4 8 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The other substitutions found in co-infected patients, E122K (44.1%), T200A (35.3%), S162C (29.4%) and D177E (26.5%) have been previously reported in studies with HIV mono-infected patients. 2018 Scientific reports Discussion HIV S162C 85 90 HIV infections 163 180 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The presence of M184V is related to early virologic failure during therapy with 3TC. 2018 Scientific reports Discussion HIV M184V 16 21 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. The resistance codons that are present include K238N and L10I, which are indicative of infection progression because these mutations are associated with high viral replication and a decreased effectiveness of PI and NNRTI class drugs. 2018 Scientific reports Discussion HIV L10I 57 61 NNRTI;PI 216;209 221;211 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. This is useful because M184V reduces viral fitness. 2018 Scientific reports Discussion HIV M184V 23 28 29844604 HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection. This patient has the following resistance codons: M41L, D67H, T69N, K70R, L74I, V118I, T215F, K219E, K219Q and K103Y. 2018 Scientific reports Discussion HIV K70R;L74I;M41L 68;74;50 72;78;54 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. Although the spectrum of NRTI-associated SDRMs was diverse, >80% of NRTI TDR cases were caused by TAMs, of which those other than T215Y/F may have little impact on currently used NRTIs. 2019 Clinical infectious diseases Discussion HIV T215F;T215Y 130;130 137;137 NRTI;NRTI;NRTI 25;68;179 29;72;184 29846534 Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population. The rarity of K65R, other less common TDF-associated mutations, and the primary TAMs T215Y/F indicates that transmitted TDF resistance is unusual. 2019 Clinical infectious diseases Discussion HIV K65R;T215F;T215Y 14;85;85 18;92;92 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. Apart from the common emergent RAMs observed in patients with first-line treatment failure in previous studies, such as M184V/I (42.3%), Y181C (42.3%), and K103N (15.5%), 28.2% of our patients with virological failure harbored K65R mutation, which was 6 times more likely to occur in those individuals receiving regimens containing TDF/FTC or TDF plus lamivudine and nevirapine. 2018 Infection and drug resistance Discussion HIV K103N;K65R;M184I;M184V;Y181C 156;227;120;120;137 161;231;127;127;142 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. First, the coadministered antiretrovirals in the first-line regimens could influence the emergence of K65R. 2018 Infection and drug resistance Discussion HIV K65R 102 106 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. If failure occurs on a TDF plus lamivudine (or FTC)-based first-line regimen with emergent K65R, zidovudine plus lamivudine should be used as the NRTI backbone in the second-line regimens before the genotypic resistance report is available. 2018 Infection and drug resistance Discussion HIV K65R 91 95 NRTI 146 150 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. In our study, single K65R mutation and resistance to TDF and coadministered drugs were only observed in patients receiving 2 NRTIs plus nevirapine (Figure 3). 2018 Infection and drug resistance Discussion HIV K65R 21 25 NRTI 125 130 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. Since the majority of these patients (40.4%) received the first-line regimens containing zidovudine, its influence on the detection of RAMs or Q151M complex can be neglected. 2018 Infection and drug resistance Discussion HIV Q151M 143 148 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. The average PVL at treatment failure was 4.42+-0.92 log10 copies/mL and 4.91+-0.68 log10 copies/mL in patients with K65R mutations (n=12) and those with K65R/M184V mutations (n=8), respectively. 2018 Infection and drug resistance Discussion HIV K65R;K65R;M184V 116;153;158 120;157;163 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. The prevalence of K65R mutation was significantly higher in our patients receiving 2 NRTIs plus nevirapine than that in those receiving efavirenz-containing regimens (44.2% vs 3.8%, p<0.001), with an AOR of 6.02 (Figure 3; Table 2), an observation similar to that reported by the TenoRes Study Group. 2018 Infection and drug resistance Discussion HIV K65R 18 22 NRTI 85 90 29892199 Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study. Therefore, the high prevalence of K65R mutation in our patients who failed the first-line regimen could provide some information on the factors associated with the emergence of RAMs to TDF. 2018 Infection and drug resistance Discussion HIV K65R 34 38 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Among the minority DRMs, detected by 454 deep sequencing, K65R and M184I were the most common and may compromise the effectiveness of both first- and second-line drugs used according to the Malawi ART guidelines. 2018 African journal of laboratory medicine Discussion HIV K65R;M184I 58;67 62;72 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. For instance, increased M184IV/I mutations would reduce susceptibility to lamivudine and emtricitabine (scores from 0 to 60, from susceptible to high-level of resistance). 2018 African journal of laboratory medicine Discussion HIV M184I;M184V 24;24 32;32 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. However, we did not find higher error rates for K65R compared with other DRM sites in these patients. 2018 African journal of laboratory medicine Discussion HIV K65R 48 52 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. In the present study, the K103N mutation was not detected from the mixed clone at 1% of minority variant level of control plasmids from 520 reads. 2018 African journal of laboratory medicine Discussion HIV K103N 26 31 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. K65R+ M184V/I would reduce susceptibility to tenofovir and didanosine from low-level (scores from 0 to 60) to high-level resistance (scores from 15 to 75). 2018 African journal of laboratory medicine Discussion HIV M184I;M184V;K65R 6;6;0 13;13;4 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. M184I was considered to be a transient mutation before being replaced by M184V. 2018 African journal of laboratory medicine Discussion HIV M184V;M184I 73;0 78;5 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. M46I/L is considered a major PI mutation and would increase drug resistance levels to PIs along with other mutations. 2018 African journal of laboratory medicine Discussion HIV M46I;M46L 0;0 6;6 PI;PI 29;86 31;89 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. No detectable levels of M184V mutations were found in pre-ART samples using deep sequencing, but M184V mutation was detected in over three-quarters of samples from patients failing ART. 2018 African journal of laboratory medicine Discussion HIV M184V;M184V 24;97 29;102 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Second, although significantly increased minority DRMs were observed in the samples collected from pre-ART and patients with virologic failure using Roche 454 barcoded deep sequencing, lack of proper plasmid mutant K65R control in the test might have compromised the accuracy of calculating the K65R mutation rate. 2018 African journal of laboratory medicine Discussion HIV K65R;K65R 215;295 219;299 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Several studies have reported that increased presence of K65R mutations is caused by pyrosequencing errors or by the nucleotide template of subtype C viruses (such as the ATA sequence at codon 63 of the RT gene). 2018 African journal of laboratory medicine Discussion HIV K65R 57 61 RT 203 205 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Similar to previous studies, the K65R mutation was seen in both treatment-naive patients and patients failing ART in this cohort. 2018 African journal of laboratory medicine Discussion HIV K65R 33 37 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Some minority K103N mutations could have been missed in this study. 2018 African journal of laboratory medicine Discussion HIV K103N 14 19 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Taken together, the higher NRTI resistance mutations of M184V and K65R in patients failing ART were more likely acquired by selective drug pressure in this Malawian cohort treated with a regimen containing stavudine and lamivudine. 2018 African journal of laboratory medicine Discussion HIV K65R;M184V 66;56 70;61 NRTI 27 31 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The H221Y mutation could also impact clinical outcomes as Y181C/H221Y along with the K103N or K101Q mutations could increase resistance levels to nevirapine over 100-fold (K103N) or 3000-fold (K101Q). 2018 African journal of laboratory medicine Discussion HIV H221Y;H221Y;K101Q;K101Q;K103N;K103N;Y181C 4;64;94;193;85;172;58 9;69;99;198;90;177;63 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The K65R mutation can confer resistance to stavudine and cross-resistance to lamivudine, abacavir, emtricitabine and tenofovir, and is more frequently identified in HIV-1 subtype C. 2018 African journal of laboratory medicine Discussion HIV K65R 4 8 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The M184I mutations were only detected at low frequencies by deep sequencing in pre-ART patients and patients with treatment failure. 2018 African journal of laboratory medicine Discussion HIV M184I 4 9 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The mutations K101E, K103N, V106A/M, V179D/T, Y181C, G190A/E and H221Y to NNRTI were the most common minority mutations detected in these patients. 2018 African journal of laboratory medicine Discussion HIV G190A;G190E;H221Y;K101E;K103N;V106A;V106M;V179D;V179T;Y181C 53;53;65;14;21;28;28;37;37;46 60;60;70;19;26;35;35;44;44;51 NNRTI 74 79 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. The natural polymorphism of M46I has been reported to have a replicative advantage for subtype B, while the impact of M46I/L natural polymorphisms on the development of drug resistance in patients is unknown. 2018 African journal of laboratory medicine Discussion HIV M46I;M46I;M46L 28;118;118 32;124;124 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. This was likely due to not having enough reads amplified for this mixed plasmid as a previous study demonstrated that at least 1950 reads are required for detecting a minority variant for K103N mutations at about the 1% level. 2018 African journal of laboratory medicine Discussion HIV K103N 188 193 29977795 Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy. Virus with K101E/Y181C/G190A and other mutations could increase levels of resistance to nevirapine 893-fold. 2018 African journal of laboratory medicine Discussion HIV G190A;K101E;Y181C 23;11;17 28;16;22 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Although the concept of a time-dependent effect likely applies to any resistance mutation (ie, the longer the time the mutation has been not detected, the lower its impact on virological outcome), the declining effect could be faster for those variants with impaired replication, such as M184V. 2018 Open forum infectious diseases Discussion HIV M184V 288 293 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Although the main results did not show a significant role for M184V, some sensitivity analyses suggested an effect on treatment efficacy. 2018 Open forum infectious diseases Discussion HIV M184V 62 67 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Although the mechanism underlying the time-dependent effect of M184V remains to be clarified, simplification to lamivudine-based DT appears safer in patients carrying M184V who have been fully virologically suppressed for a longer period. 2018 Open forum infectious diseases Discussion HIV M184V;M184V 63;167 68;172 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Based on our findings, a previous selection of M184V should not represent a major obstacle to the efficacy of these regimens, provided that viral suppression has been consolidated and the activity of the drug accompanying lamivudine is fully preserved. 2018 Open forum infectious diseases Discussion HIV M184V 47 52 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. DTs were also more effective than bPI monotherapies, independently from M184V. 2018 Open forum infectious diseases Discussion HIV M184V 72 77 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Here we show that a previous selection of the M184V mutation has no major impact on the virological efficacy of lamivudine-based DT as a maintenance regimen. 2018 Open forum infectious diseases Discussion HIV M184V 46 51 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In a prospective study of 27 patients, 8 carried the M184V mutation in their hGRT, and none of them experienced virological failure in the first year of DT, whereas in a cohort of 36 patients switching to this dual regimen, 3 had a prior detection of M184V, and none of these experienced virological failure. 2018 Open forum infectious diseases Discussion HIV M184V;M184V 53;251 58;256 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In line with Mobidip, we also show lower rates of virologic failure with DT than with bPI monotherapy, even in patients harboring M184V, even though only the comparison between DT overall vs monotherapy reached statistical significance, not the one between DT with previous selection of the M184V vs monotherapy, probably due to the limited sample size. 2018 Open forum infectious diseases Discussion HIV M184V;M184V 130;291 135;296 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In particular, in patients with a shorter duration of viral suppression before simplification to DT, the group with previous detection of M184V showed higher hazards of virological failure, and the gap of efficacy between the groups increased when reducing the duration of suppression, particularly below 3 years. 2018 Open forum infectious diseases Discussion HIV M184V 138 143 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. In that study, all patients had a previous virological failure on a NNRTI-based firstline therapy, and their viruses harbored multiple mutations (97% had M184V, 59% at least 1 and 27% at least 3 thymidine analogue mutations). 2018 Open forum infectious diseases Discussion HIV M184V 154 159 NNRTI 68 73 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Interestingly, in our cohort, 21 patients on lamivudine plus dolutegravir carried M184V, and none failed after a median follow-up of 10 months, whereas dolutegravir maintenance monotherapy studies have shown measurable failure rates during follow-up of similar duration. 2018 Open forum infectious diseases Discussion HIV M184V 82 87 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. It has to be highlighted that the chosen comparator was PI monotherapy, not triple therapy, to test whether the lamivudine-based DT in patients carrying M184V could be considered "functional" monotherapy. 2018 Open forum infectious diseases Discussion HIV M184V 153 158 PI 56 58 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Measuring the dynamics of M184V HIV-DNA relative to total HIV-DNA levels over time under suppressive therapy would be required to test this hypothesis. 2018 Open forum infectious diseases Discussion HIV M184V 26 31 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Moreover, recent in vitro studies indicated a protective role of M184V against the selection of dolutegravir resistance mutations, further explaining the lack of impact of this mutation on the efficacy of lamivudine plus dolutegravir. 2018 Open forum infectious diseases Discussion HIV M184V 65 70 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Moreover, we found no impact of previous M184V detection of the durability of lamivudine-based DT. 2018 Open forum infectious diseases Discussion HIV M184V 41 46 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Multivariable analysis adjusting for factors differing between the M184V-positive and -negative groups at DT initiation confirmed the lack of association of this substitution with virological failure. 2018 Open forum infectious diseases Discussion HIV M184V 67 72 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Nonetheless, when we adjusted the analyses for these characteristics in several multivariable models, still no impact of M184V on virological failure was found. 2018 Open forum infectious diseases Discussion HIV M184V 121 126 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Observational studies with small sample size and short follow-up also support the view that past M184V has no impact on the efficacy of lamivudine plus dolutegravir. 2018 Open forum infectious diseases Discussion HIV M184V 97 102 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. One possible explanation for the absence of a major negative impact of the prior M184V mutation on the efficacy of lamivudine-based DT could be its association with decreased viral fitness and with lower replication capacity, lowering the probability of virus rebound. 2018 Open forum infectious diseases Discussion HIV M184V 81 86 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. Our study confirms the efficacy of lamivudine-based DT in patients previously selecting the M184V mutation, despite relevant differences between the 2 studies in term of design, resource setting, population characteristics, and virological failure definition. 2018 Open forum infectious diseases Discussion HIV M184V 92 97 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The achieved statistical power to detect differences between M184V groups for the main virological failure end point was low. 2018 Open forum infectious diseases Discussion HIV M184V 61 66 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. The higher rate of viral blips in patients with past M184V confirms that previous selection of M184V has some negative effect on maintaining complete viral suppression. 2018 Open forum infectious diseases Discussion HIV M184V;M184V 53;95 58;100 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. This finding was consistent throughout several sensitivity analyses using different classifications of M184V detection and virological failure. 2018 Open forum infectious diseases Discussion HIV M184V 103 108 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. This is the first study directly comparing the efficacy of lamivudine-based DT in patients with or without previous detection of the M184V substitution. 2018 Open forum infectious diseases Discussion HIV M184V 133 138 29977967 Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study. This trend is compatible with a progressive decline of the impact of M184V with increasing time since the mutation was last detected. 2018 Open forum infectious diseases Discussion HIV M184V 69 74 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. T215C is considered a revertant mutation that do not reduce NRTI susceptibility but indicate that this virus population once contained T215Y/F mutations. 2018 PloS one Discussion HIV T215F;T215Y;T215C 135;135;0 142;142;5 NRTI 60 64 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. This mutation suggests that the patient may have once harbored a majority virus population with T215Y/F. 2018 PloS one Discussion HIV T215F;T215Y 96;96 103;103 30016324 HIV-1 infection among crack cocaine users in a region far from the epicenter of the HIV epidemic in Brazil: Prevalence and molecular characteristics. This patient's virus had M41L mutation which is a TAM that usually occurs with T215Y conferring high-level resistance to AZT and d4T and intermediate-level resistance to ddI, ABC and TDF. 2018 PloS one Discussion HIV M41L;T215Y 25;79 29;84 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. All multi-drug-resistant viruses were observed to have a statistically significant increase in viral fitness under AZT-selective pressure, except viruses harboring the T69SSS insertion complex without A62V (Figure 5B). 2018 Viruses Discussion HIV A62V;T69SSS 201;168 205;174 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. As anticipated, viruses harboring the A62V mutation alone had the most significant reduction in replication capacity. 2018 Viruses Discussion HIV A62V 38 42 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. As previously reported, we observed that the fitness of the Q151M complex, in the presence or absence of the A62V mutation, was not significantly different than that of the wt virus (Figure 5A). 2018 Viruses Discussion HIV A62V;Q151M 109;60 113;65 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Both the Q151M complex and the T69SSS insertion complex share the A62V secondary drug-resistance-associated point mutation, which is located close to the active polymerization site of HIV-1 RT (Figure 6A,B, respectively). 2018 Viruses Discussion HIV A62V;Q151M;T69SSS 66;9;31 70;14;37 RT 190 192 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. How A62V influences replication is currently unclear, and will be a topic of future analyses. 2018 Viruses Discussion HIV A62V 4 8 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. However, viruses harboring the Q151M complex without A62V had a higher level of drug resistance than that of viruses possessing the Q151M complex with A62V (Figure 4), which agrees with previous reports. 2018 Viruses Discussion HIV A62V;A62V;Q151M;Q151M 53;151;31;132 57;155;36;137 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In contrast, the two MDR variant viruses with A62V, along with the virus harboring the A62V mutant alone, had a lower replication capacity relative to wt HIV-1 (Figure 3). 2018 Viruses Discussion HIV A62V;A62V 46;87 50;91 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In contrast, viruses harboring the Q151M complex or the T69SSS insertion complex in the context of A62V had replication efficiencies comparable to that of wt HIV-1 in the absence of a drug when under AZT drug-selective pressure (Figure 4). 2018 Viruses Discussion HIV A62V;Q151M;T69SSS 99;35;56 103;40;62 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In particular, we used parallel analyses to look at the relationship between HIV-1 fitness and mutagenesis in the presence or absence of the RT A62V amino acid substitution. 2018 Viruses Discussion HIV A62V 144 148 RT 141 143 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In summary, the observations made in this study provide the first demonstration that A62V is an important adaptive mutation in multi-drug-resistant viruses that impacts the interplay of replication fidelity, virus fitness and drug susceptibility. 2018 Viruses Discussion HIV A62V 85 89 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. In the presence of AZT (Figure 2B), the mutant frequency of all the MDR viruses, except that of the T69SSS insertion complex without A62V, were restored to that of wt HIV-1 in the absence of AZT. 2018 Viruses Discussion HIV A62V;T69SSS 133;100 137;106 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Taken together, these data support the conclusion that both MDR variant viruses (i.e., harboring the Q151M complex and the T69SSS insertion complex mutations), in the context of the A62V amino acid substitution, had mutant frequencies and replication capacities, when under AZT selective pressure, comparable to that of the wt virus in the absence of drug-selective pressure. 2018 Viruses Discussion HIV A62V;Q151M;T69SSS 182;101;123 186;106;129 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Taken together, these observations support the conclusion that the T69SSS insertion complex does not confer a fitness advantage in the absence of AZT (Figure 5A), but does improve fitness in the presence of AZT (Figure 5B). 2018 Viruses Discussion HIV T69SSS 67 73 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The replicative capacity of viruses harboring the MDR Q151M complex, in the presence or absence of the A62V mutation, was observed to be comparable under AZT drug pressure (Figure 5B). 2018 Viruses Discussion HIV A62V;Q151M 103;54 107;59 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. The T69SSS insertion complex without A62V was observed to possess the highest replication capacity. 2018 Viruses Discussion HIV A62V;T69SSS 37;4 41;10 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. These observations support the conclusion that the A62V mutation plays an important role in RT fidelity by increasing mutant frequency (Figure 2), where mutant frequency is higher in the context of MDR complexes in the absence of AZT (Figure 2A), but highest in virus with the A62V mutation alone in the presence of AZT (Figure 2B). 2018 Viruses Discussion HIV A62V;A62V 51;277 55;281 RT 92 94 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. These observations, together with the observations made of the relative susceptibility to AZT (Figure 4), indicate that the MDR viruses without A62V analyzed in our study have reduced AZT drug susceptibility at the expense of replication capacity. 2018 Viruses Discussion HIV A62V 144 148 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. This conclusion agrees with previous observations regarding the increased fitness associated with the T69SSS insertion complex during drug-selective pressure. 2018 Viruses Discussion HIV T69SSS 102 108 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. This was most notable with the viruses harboring the T69SSS insertion complex in the absence of the A62V mutation. 2018 Viruses Discussion HIV A62V;T69SSS 100;53 104;59 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. To investigate this, we tested the hypothesis that A62V provides a selective advantage to the virus in the context of multi-drug resistance by influencing replication fidelity and fitness. 2018 Viruses Discussion HIV A62V 51 55 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Together, these observations implicate A62V as an adaptive mutation arising via drug pressure. 2018 Viruses Discussion HIV A62V 39 43 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. Under AZT-selective pressure, viruses harboring either the Q151M complex or the T69SSS insertion complex without A62V had the lowest level of drug susceptibility. 2018 Viruses Discussion HIV A62V;Q151M;T69SSS 113;59;80 117;64;86 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. We first found that the A62V mutation alone could significantly increase viral mutant frequencies (Figure 2), while negatively impacting replication capacity (Figure 3 and Figure 4) and viral fitness (Figure 5) in the absence or presence of AZT. 2018 Viruses Discussion HIV A62V 24 28 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. We observed that MDR mutants without the A62V mutation had the lowest mutant frequencies, suggesting that these RT variants have higher fidelity (Figure 2A). 2018 Viruses Discussion HIV A62V 41 45 RT 112 114 30029500 The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations. While the A62V amino acid substitution in HIV-1 RT is known to be associated with multi-drug resistance, it is not a resistance-conferring mutation, and its appearance remains an open question in the field. 2018 Viruses Discussion HIV A62V 10 14 RT 48 50 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. The most prevalent NNRTI mutation that was detected in the studied population was K103N, which is associated with the use of Nevirapine - also a major component of first line regimens in Kenya. 2018 The Pan African medical journal Discussion HIV K103N 82 87 NNRTI 19 24 30061964 Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis. The most prevalent NRTI drug resistant mutation was M184V that has been associated with use of lamivudine. 2018 The Pan African medical journal Discussion HIV M184V 52 57 NRTI 19 23 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Based on structure-guided cysteine pair analysis, we found that A501C-L663C (CC2) forms an inter-protomer disulfide bond that stabilizes the original uncleaved NFL trimer. 2018 Frontiers in immunology Discussion HIV A501C;L663C 64;70 69;75 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Here, the L555P identified in our P screen is comparable to or even better than I559P in some NFL contexts but is not compatible with the BG505 SOS backbone in this regard, indicating additional advantages of the NFL design to accept specific engraftments, perhaps since it lacks the engineered 501-605 disulfide. 2018 Frontiers in immunology Discussion HIV I559P;L555P 80;10 85;15 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Here, we identified a new cysteine pair called CC2 (A501C-L663C) that forms an inter-protomer disulfide bond and increases the thermostability of multiple NFLs, augmenting trimer formation while maintaining desired antigenicity. 2018 Frontiers in immunology Discussion HIV A501C;L663C 52;58 57;63 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. In terms of well-ordered soluble NFL trimer formation, the L555P substitution is the most comparable to, and in some context, even superior to the I559P substitution. 2018 Frontiers in immunology Discussion HIV I559P;L555P 147;59 152;64 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Mutations K574R and I535M in HR1 are reported to increased Env stability in different clades, and V570D and I573D can destabilize the 6-HB formation, favoring the prefusion state on the cell-surface, independent of the I559P substitution. 2018 Frontiers in immunology Discussion HIV I535M;I559P;I573D;K574R;V570D 20;219;108;10;98 25;224;113;15;103 Env 59 62 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Size exclusion chromatography analyses of NFL TD 2CC+ D4K trimers reveals that I559P is more compatible with the CC2 and TD CC+ modifications than is either the L555P or Q563P substitutions (data not shown), indicating that further optimization is needed to render the L555P more compatible in combination with the CC2 and TD CC+ substitutions. 2018 Frontiers in immunology Discussion HIV I559P;L555P;L555P;Q563P 79;161;269;170 84;166;274;175 30065725 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. The SOS-defined I559P substitution is an important modification to stabilize soluble trimer mimics in the prefusion conformation for SOSIPs, single-chain gp140, DS-SOSIP, and the NFL trimers. 2018 Frontiers in immunology Discussion HIV I559P 16 21 gp140 154 159 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. (2015) where K103N was associated to resistance to NVP and EFV, in this study this mutation was not associated to any NNRTI. 2018 Journal of public health in Africa Discussion HIV K103N 13 18 NNRTI 118 123 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. As reported in other studies, M184V was the most frequent in this study and was associated with high-level resistance to 3TC, FTC, and ABC. 2018 Journal of public health in Africa Discussion HIV M184V 30 35 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Mutation K65R, which was reported as a major mutation conferring high-level resistance to most of NRTI, this mutation was associated with intermediate resistance to 3TC in this study. 2018 Journal of public health in Africa Discussion HIV K65R 9 13 NRTI 98 102 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Mutations Y181C, G190A conferred high resistance to EFV and NVP in mothers and infants. 2018 Journal of public health in Africa Discussion HIV G190A;Y181C 17;10 22;15 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Other studies reported mutations G190A, Y181C that conferred high resistance to NNRTI in individuals with subtype C. 2018 Journal of public health in Africa Discussion HIV G190A;Y181C 33;40 38;45 NNRTI 80 85 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Others mutations detected such as T215F/Y, D67N/E, K70R, and K219Q are associated with intermediate resistance to TDF, AZT, and 3TC. 2018 Journal of public health in Africa Discussion HIV D67E;D67N;K219Q;K70R;T215F;T215Y 43;43;61;51;34;34 49;49;66;55;41;41 30079168 Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso. Some studies also found K103N and Y181C in individuals with subtypes A, B, C, F and CRF02_AG who developed resistance to NVP, ETR, and EFV. 2018 Journal of public health in Africa Discussion HIV K103N;Y181C 24;34 29;39 30085096 HIV-1 Vpr and p21 restrict LINE-1 mobility. We showed that the inhibitory effect of a mutant Vpr (H71R), which is unable to arrest the cell cycle, was significantly reduced compared with that of wild-type Vpr (Figure 3E and F), suggesting that Vpr suppresses L1 mobility in a cell cycle dependent manner. 2018 Nucleic acids research Discussion HIV H71R 54 58 Vpr;Vpr;Vpr 49;161;200 52;164;203 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. A larger panel of viral isolates are needed to address the potential development of the Q148R/K resistance pathway with CAB. 2018 Retrovirology Discussion HIV Q148K;Q148R 88;88 95;95 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Although 4/12 and 6/12 selections with CAB, yielded no resistance or minor resistance, respectively, two selections with CAB (one subtype B and one CRF02_AG), resulted in the acquisition of Q148R/K with multiple secondary resistance substitutions conferring high-level cross-resistance to all INSTIs. 2018 Retrovirology Discussion HIV Q148K;Q148R 190;190 197;197 INSTI 293 299 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In previous studies, subtype C variant, 4742, developed the G118R mutation in cell culture selections with DTG and Merck investigation INSTI, MK2048. 2018 Retrovirology Discussion HIV G118R 60 65 INSTI 135 140 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In selections of two clinical isolates and a patient-derived recombinant strain, resistance to CAB arose through a Q148R. 2018 Retrovirology Discussion HIV Q148R 115 120 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In the remaining selections, the acquisition of singleton R263K, S153Y/F or H51Y substitutions conferred low-level resistance, regardless of viral subtype. 2018 Retrovirology Discussion HIV H51Y;R263K;S153F;S153Y 76;58;65;65 80;63;72;72 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. In this study, the 4742-viral strain gave rise to no resistance with either DTG or BIC, R263KR with CAB, and E92EG/R263K with EVG. 2018 Retrovirology Discussion HIV E92E;E92G;R263K;R263K;R263R 109;109;88;115;88 114;114;94;120;94 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The CAB, an analogue of DTG with high potency, may be prone to the development of Q148K/R leading to cross-resistance to the entire class of integrase inhibitors. 2018 Retrovirology Discussion HIV Q148K;Q148R 82;82 89;89 IN 141 150 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The development of G118R was associated with a rare GGA natural polymorphism at codon 118, facilitating a G to A transition leading to G118R (AGA). 2018 Retrovirology Discussion HIV G118R;G118R 19;135 24;140 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The first appearance of Q148R showed < 3-fold resistance to CAB, DTG and BIC. 2018 Retrovirology Discussion HIV Q148R 24 29 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The observed emergence of resistance through the Q148R pathway may lead to cross-resistance to the entire class of INSTIs. 2018 Retrovirology Discussion HIV Q148R 49 54 INSTI 115 121 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The potential steric interactions induced by Q148R at and near the beta4-alpha2 loop may affect binding kinetics of CAB, leading to a decreased dissociative half-life with Q148R between that of DTG and RAL. 2018 Retrovirology Discussion HIV Q148R;Q148R 45;172 50;177 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The selection of Q148R in CAB selections is consistent with the observed acquisition of Q148R in two patients in the Latte clinical trials. 2018 Retrovirology Discussion HIV Q148R;Q148R 17;88 22;93 30119633 Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. The sequential accumulation of mutations by these three strains resulted in Q148R/E138K/R263K/L74M, Q148K/G140S/S147G/L74M and Q148R/E138K/L74I/G140GS mutational motifs conferring in high-level cross-resistance to all five INSTIs. 2018 Retrovirology Discussion HIV E138K;E138K;G140G;G140S;G140S;G140S;L74I;L74M;L74M;Q148K;Q148R;Q148R;R263K;S147G 82;133;144;144;106;144;139;94;118;100;76;127;88;112 87;138;149;149;111;151;143;98;122;105;81;132;93;117 INSTI 223 229 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. Notably, the wild-type and Y86F SIVcol Nefs represent useful tools to examine the relevance of SERINC5 counteraction for viral replication in vivo. 2018 PLoS pathogens Discussion HIV Y86F 27 31 Nef 39 43 30125328 SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue. These effects were disrupted by a single point mutation of Y86F allowing us to analyze the relevance of potent anti-SERINC5 antagonism by Nef for viral replication and cytopathicity. 2018 PLoS pathogens Discussion HIV Y86F 59 63 Nef 138 141 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Although EFdA showed slightly elevated IC50 value with 2.7-fold change, it still maintained its antiviral activity with an IC50 value of sub nano molar, indicating that 4'-ethynyl NRTIs including EFdA showed increased potency against HIV-1K65R. 2018 Cell chemical biology Discussion HIV K65R 239 243 NRTI 180 185 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. EFdA also retained its potency against the viruses containing not only M184V/I mutation, but also E138K mutation, which caused virological failure during the clinical trials that evaluated rilpivarine with emtricitabine as a first-line therapy. 2018 Cell chemical biology Discussion HIV E138K;M184I;M184V 98;71;71 103;78;78 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Four compounds that contain 4'-ethynyl moiety (Figure 1), showed increased potency against HIV-1K65R compared to that against HIV-1WT (Table 1). 2018 Cell chemical biology Discussion HIV K65R 96 100 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. In the present study, we had assessed the anti-viral activity of a series of 4'-NRTIs against HIV-1K65R and found that these 4'-NRTIs also maintained their antiviral activity. 2018 Cell chemical biology Discussion HIV K65R 99 103 NRTI;NRTI 80;128 85;133 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Interestingly, the Y115F mutation is reported to be associated with the HIV-1 drug (ABC and TDF) resistance and is the only amino acid substitution that does not reduce the HIV-1 RT enzyme activity. 2018 Cell chemical biology Discussion HIV Y115F 19 24 RT 179 181 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. It was reported that EFdA showed hypersensitivity against K65R mutation, which is known as a TDF-resistant associated mutation. 2018 Cell chemical biology Discussion HIV K65R 58 62 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. The K65R substitution causes minor changes in the efficacy of EFdA incorporation and of RT translocation, causes the hypersensitivity of EFdA against K65R mutation. 2018 Cell chemical biology Discussion HIV K65R;K65R 4;150 8;154 RT 88 90 30174310 The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. The results of the present study also suggest another strategy to design NRTIs that directly bind to residues that are critical for the function of HIV-1 RT (e.g., F160) or HBV RT even in the presence of drug-resistant mutations, such as (e.g., M184V). 2018 Cell chemical biology Discussion HIV M184V 245 250 NRTI;RT;RT 73;154;177 78;156;179 30219320 Genome-scale analysis of evolutionary rate and selection in a fast-expanding Spanish cluster of HIV-1 subtype F1. However, the positively selected positions detected, and particularly nef H89F, might be associated with the already reported high plasma viral loads in the infected patients, that could have facilitated transmission. 2018 Infection, genetics and evolution Discussion HIV H89F 74 78 Nef 70 73 30219320 Genome-scale analysis of evolutionary rate and selection in a fast-expanding Spanish cluster of HIV-1 subtype F1. One of these positions, nef H89F, has been reported to be associated with immune escape from CD8+ T cells. 2018 Infection, genetics and evolution Discussion HIV H89F 28 32 Nef 24 27 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. A98G is a minor mutation found in one drug-naive participant (KDC1/1) and causes 5fold and 3fold reduced susceptibility to NVP and EFV respectively. 2018 Virology journal Discussion HIV A98G 0 4 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. E138A mutation in the RT gene was seen in this group and though it does not cause reduction in susceptibility to NVP and EFV, it confers low-level resistance to RPV and ETR, other NNRTIs not used in Ghana, pointing to another case of cross-resistance. 2018 Virology journal Discussion HIV E138A 0 5 NNRTI;RT 180;22 186;24 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. For the mothers who were on ART after prophylaxis in the PMTCT programme, the HIV-1 drug resistance associated mutations seen were dominated by M184 V for NRTIs and Thymidine Analogue-Associated Mutations (TAMS) including M41 L and T215Y; and K103 N with A98G for NNRTIs. 2018 Virology journal Discussion HIV A98G;K103N;M184V;M41L;T215Y 255;243;144;222;232 259;249;150;227;237 NNRTI;NRTI 264;155 270;160 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Furthermore, A98G found in the group causes reduction in susceptibility to NVP by 5-fold and to EFV by 3-fold and has the ability to cause reduction in other members of the NNRTIs not in use in Ghana such as Etravirine (ETR) and Rilpivirine (RPV). 2018 Virology journal Discussion HIV A98G 13 17 NNRTI 173 179 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Generally, it is known that mutations selected by TAMS confer resistance to internationally approved NRTIs; examples of such TAMS encountered in the study are M41 L, D67N, K70R, L210 W, T215Y/F and K219Q/E. 2018 Virology journal Discussion HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 166;198;198;172;178;159;186;186 170;205;205;176;184;164;193;193 NRTI 101 106 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. However, in the other mothers in this group, M184 V occurred with Thymidine Analogue-Associated Mutations (K70R, K219E, M41 LM and T215I); it therefore produced a synergistic effect that led to different levels of reduction in susceptibility. 2018 Virology journal Discussion HIV K219E;K70R;M184V;T215I 113;107;45;131 118;111;51;136 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. K103 N and V106A are major mutations associated with NNRTIs conferring high-level HIV-1 drug resistance to NVP and EFV. 2018 Virology journal Discussion HIV K103N;V106A 0;11 6;16 NNRTI 53 59 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. K103 N was seen in all the participants in the Prophylaxis plus ART Group (Group 1) and caused high-level resistance to NVP and EFV. 2018 Virology journal Discussion HIV K103N 0 6 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. L210 W is a TAM, a major mutation detected in one participant in this group (KDC1/10); it confers low-level resistance to all NRTIs in use in Ghana except 3TC and FTC. 2018 Virology journal Discussion HIV L210W 0 6 NRTI 126 131 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. M184 V as a stand-alone mutation, results in a clinically significant reduction in HIV-1 replication in the patient. 2018 Virology journal Discussion HIV M184V 0 6 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Mutation I84V emerged in the Protease gene associated with resistance to the PIs recommended for use in Ghana, ie NFV and Ritonavir boosted Lopinavir (LPV/r). 2018 Virology journal Discussion HIV I84V 9 13 PR;PI 29;77 37;80 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. NNRTIs resistance mutations Y181C and M230 L are known to confer high-level and intermediate resistance to NVP and EFV. 2018 Virology journal Discussion HIV Y181C 28 33 NNRTI 0 6 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. One patient (KDC1/6) had M184 V mutation which is a major mutation in the RT gene associated with NRTIs and known to confer high-level resistance to 3TC and FTC, low-level resistance to DDI and ABC. 2018 Virology journal Discussion HIV M184V 25 31 NRTI;RT 98;74 103;76 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. Resistance mutation to NRTIs seen in the group of drug-experienced without prophylaxis mothers was M184 V. 2018 Virology journal Discussion HIV M184V 99 105 NRTI 23 28 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The presence of A98G in these mothers could confer high-level resistance to NVP and EFV. 2018 Virology journal Discussion HIV A98G 16 20 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The presence of M184 V with TAMs confer resistance to all the ARVs available to the patient, resulting in no useful option in NRTIs the this category of patients (Table 3). 2018 Virology journal Discussion HIV M184V 16 22 NRTI 126 131 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The presence of Y181C, M230 L and M230 LM posed resistance to all the NNRTIs used in the country for this group of people (the prophylaxis plus ART group). 2018 Virology journal Discussion HIV M230L;M230L;Y181C 23;34;16 29;40;21 NNRTI 70 76 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The resistance associated mutation in the RT gene to NNRTIs (NVP & EFV) seen in this group was A98G; this was found in two of the participants who had been on treatment for almost 6 years. 2018 Virology journal Discussion HIV A98G 95 99 NNRTI;RT 53;42 59;44 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. The V75S mutation is weakly selected by NRTIs and thus confers a low-level resistance to DDI and D4T. 2018 Virology journal Discussion HIV V75S 4 8 NRTI 40 45 30223845 Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana. When K103 N is seen in combination with L100I as seen in this group, it confers high-level resistance to both NVP and EFV, leaving the patient with only the AZT and 3TC combination to counter the virus. 2018 Virology journal Discussion HIV K103N;L100I 5;40 11;45 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Additional analysis of the breadth of the T cell responses to RTVY10, NefRY11, and NefYF9 epitopes showed a strong correlation with lower pVL in the Y135F-infected individuals, although even responders to 3 epitopes had a relatively high pVL for our cohort (median: 14,000 copies/mL). 2018 EBioMedicine Discussion HIV Y135F 149 154 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. HLA-A*24:02 is found in 19% and 34% of Caucasians and Mexicans, respectively, while Y135F was found in >80% of Caucasians expressing this HLA allele. 2018 EBioMedicine Discussion HIV Y135F 84 89 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. In addition, there was no significant difference between A*24:02+ and A*24:02- in individuals infected with either the Y135F mutant virus or those with WT virus. 2018 EBioMedicine Discussion HIV Y135F 119 124 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Responders to one of these peptides in whom the Y135F mutant had emerged had a significantly higher pVL than that of WT-infected responders (median: 57,500 copies/mL vs 18,500 copies/mL. 2018 EBioMedicine Discussion HIV Y135F 48 53 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. The present study demonstrated that HIV-1 pVL is controlled to a moderate extent by multiple CD8+ T cell responses to p17NY9, RTVY10, NefRY11, and NefYF9 epitopes rather than NY10-specific T cells and shows that the control of HIV-1 by NefYF9-specific T cells is impaired by the HLA-A*24:02-associated Y135F mutation within the epitope. 2018 EBioMedicine Discussion HIV Y135F 302 307 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. The present study revealed that Y135F-infected responders to YF9 had significantly lower pVL than the Y135F-infected non-responders, although both had relatively high pVL. 2018 EBioMedicine Discussion HIV Y135F;Y135F 32;102 37;107 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. This finding suggests that the mutant epitope-specific HLA-B*35:01-restricted T cells, which are elicited after the emergence of the mutant virus, may suppress replication of the Y135F virus to some extent. 2018 EBioMedicine Discussion HIV Y135F 179 184 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Thus, accumulation of the Nef Y135F mutation, which is strongly associated with HLA-A*24:02, impaired the T-cell response to the YF9 epitope, resulting in a loss of HIV-1 control by YF9-specific CTLs. 2018 EBioMedicine Discussion HIV Y135F 30 35 Nef 26 29 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Thus, the emergence of the Y135F mutant had a distinct impact on T cells specific for the overlapping RW8 and RF10 epitopes. 2018 EBioMedicine Discussion HIV Y135F 27 32 30249546 Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control. Thus, the Y135F mutation, which occurs commonly in Japan, is a critical factor underlying the detrimental effect of HLA-B*35:01 on disease outcome in HIV-1-infected individuals expressing that allele. 2018 EBioMedicine Discussion HIV Y135F 10 15 HIV infections 150 164 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. An inhibitor capable of forming strong interactions with residues 45-47 of the flaps might assist in retaining a closed conformation dimer, and be effective against resistant mutants with defects such as those observed for L76V. 2018 ACS omega Discussion HIV L76V 223 227 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Drug-resistant mutation L76V is rare in clinical isolates of HIV; however, this mutation alone acts to decrease the stability of the PR dimer, alters precursor processing, and reduces viral fitness. 2018 ACS omega Discussion HIV L76V 24 28 PR 133 135 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Flap mutation M46I is strongly associated with L76V as shown by a large proportion of coprevalence in L76V-containing sequences. 2018 ACS omega Discussion HIV L76V;L76V;M46I 47;102;14 51;106;18 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. If the virus accumulates additional mutations, as observed in 3.2% of clinical samples, these mutations might compensate for the loss of stability because of L76V, while retaining resistance to a specific drug. 2018 ACS omega Discussion HIV L76V 158 162 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Impaired autoprocessing of precursor PR-containing L76V is partly rescued by addition of a second mutation of M46I and, although L76V reduces viral replication, viral fitness is partly rescued by combination with this mutation. 2018 ACS omega Discussion HIV L76V;L76V;M46I 51;129;110 55;133;114 PR 37 39 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. In contrast, L76V is associated with increased susceptibility to 6 and atazanavir, and experiments suggest that L76V re-sensitizes multi-drug resistant viruses to therapy with those two inhibitors. 2018 ACS omega Discussion HIV L76V;L76V 13;112 17;116 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Interestingly, five of the seven residues adjacent to Leu76 in the PR structure are sites of major resistance mutations, D30N, V32I, I47V, Q58E, and T74P2. 2018 ACS omega Discussion HIV D30N;I47V;Q58E;V32I 121;133;139;127 125;137;143;131 PR 67 69 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Mutation L76V is not unusual in this respect; mutations L90M and N88D/S also have no direct interactions with inhibitors, yet are strongly associated with resistance to one or more clinical inhibitors. 2018 ACS omega Discussion HIV L76V;L90M;N88D;N88S 9;56;65;65 13;60;71;71 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Mutation L76V, which is associated with resistance to 1, is selected during viral passage with increasing concentrations of 1. 2018 ACS omega Discussion HIV L76V 9 13 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. Of these, only the resistance mutation Q58E is strongly associated with L76V in resistant mutants. 2018 ACS omega Discussion HIV L76V;Q58E 72;39 76;43 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. The effects of combining L76V with other mutations on the structure and dynamics of the PR dimer have not yet been explored. 2018 ACS omega Discussion HIV L76V 25 29 PR 88 90 30288468 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease. The rarity of L76V as a single mutation in clinical samples, at 0.4%, may be due to its debilitating effects on precursor processing. 2018 ACS omega Discussion HIV L76V 14 18 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. An association between clustering and increased transmission of viruses harbouring NNRTI DRMs, including the G190A DRM found here, has been described in Quebec, Canada. 2018 PloS one Discussion HIV G190A 109 114 NNRTI 83 88 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. Importantly, we show that the G190A mutation has spread in Gondar by rapid transmission within local clusters. 2018 PloS one Discussion HIV G190A 30 35 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. In the present study, we identified one cluster with the G190A mutation with onward transmissions of this DRM for at least 8 years (2003-2010). 2018 PloS one Discussion HIV G190A 57 62 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. The G190A mutation represents a slowly reverting HIVDR mutation and when such mutations are present in a population with frequent transmission it might persist and expand. 2018 PloS one Discussion HIV G190A 4 9 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. The specific NNRTI associated mutations found in this study (K103N, G109S and Y181C) have been reported to account for the most common NNRTI-associated mutations in all world regions and HIV subtypes. 2018 PloS one Discussion HIV G109S;K103N;Y181C 68;61;78 73;66;83 NNRTI;NNRTI 13;135 18;140 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. Using a linear projection the cluster could be up to 75 times larger, i.e cluster 12 with 32 individual specimens may represent 2400 individual or more in the cluster (which could be compared with the estimated number of effective infections in 2013 of 2400 of the demographic plot analysis; S1 Table) and the G190A associated subcluster 12a of about 450 individuals. 2018 PloS one Discussion HIV G190A 310 315 30304061 HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013. We estimated that the entire large cluster and the G190A cluster had transmission intervals at least every year. 2018 PloS one Discussion HIV G190A 51 56 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. After evaluating 184 genotyping tests from patients during the first virologic failure, we found a higher prevalence of subtype B, of the M184 V/I and K103 N mutations, as well as a high frequency of NRTI(t) and NNRTI-associated mutations, with no impact on virologic suppression. 2018 BMC infectious diseases Discussion HIV K103N;M184I;M184V 151;138;138 157;146;146 NNRTI;NRTI 212;200 217;204 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. All the genotype sequences of the non-B subtype (F and BF) had the M184 V/I mutation, probably due to the high prevalence of this mutation and the very low frequency of non-B subtypes in our study. 2018 BMC infectious diseases Discussion HIV M184I;M184V 67;67 75;75 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. However, some studies have shown that NVP-containing ARVs have repercussions on the response to etravirine for selecting the Y181C and G190A mutations, whereas the K103 mutation associated with EFV does not interfere with etravirine susceptibility. 2018 BMC infectious diseases Discussion HIV G190A;Y181C 135;125 140;130 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. Similar to our results, the high prevalence of M184 V/I mutations was reported in several regions of Brazil, in Sub-Saharan Africa and in Asia, but to a lesser extent in western Europe. 2018 BMC infectious diseases Discussion HIV M184I;M184V 47;47 55;55 30314470 Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure. The K103 N/S mutation was documented in most genotypic sequences, due to the frequent use of EFV as the primary NNRTI in the first-line therapy for more than a decade in Brazil. 2018 BMC infectious diseases Discussion HIV K103N;K103S 4;4 12;12 NNRTI 112 117 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (ii) P122A and I124A mutants exhibit a defect in Gag processing which results in reduced levels of mature CA in mutant virions relative to the WT. 2018 mBio Discussion HIV I124A;P122A 15;3 20;10 Gag;Capsid 49;106 52;108 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. (iii) P122A and I124A mutant virions contain an elevated level of the CA-SP1 processing intermediate relative to the WT virions. 2018 mBio Discussion HIV I124A;P122A 16;4 21;11 SP1;Capsid 73;70 76;72 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Although our data demonstrate that mutation of the PPIP(122-125) motif blocks the formation of an ordered, immature Gag lattice, EM analysis of P122A and I124A virions revealed heterogeneous particles with diverse structural defects, i.e., particles with patches of Gag-like lattices and condensed or dispersed viral material and a complete absence of mature, conical cores. 2018 mBio Discussion HIV I124A;P122A 154;144 159;149 Gag;Gag 116;266 119;269 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Among the changes identified, only a combination of V11I and T58A mutations led to nearly complete recovery of virus particle production, virion infectivity, and multicycle replication. 2018 mBio Discussion HIV T58A;V11I 61;52 65;56 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Despite the highly conserved nature of the HIV-1 PPIP(122-125) motif, a mutation of either P123 or P125 to Ala is relatively well tolerated in terms of virus assembly, although P125A exhibits a severe infectivity defect. 2018 mBio Discussion HIV P125A 177 182 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Despite the severe defects in immature lattice assembly induced by the P122A and I124A mutations, these CA-NTD substitutions do not prevent MIs from blocking CA-SP1 processing. 2018 mBio Discussion HIV I124A;P122A 81;71 86;76 SP1;Capsid;Capsid 161;104;158 164;106;160 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. In contrast, mutation of either P122 or I124 markedly impairs virus assembly; aberrant Gag lattices are also observed at sites of P122A and I124A assembly at the PM of virus-producing cells, indicating severe defects at early stages of assembly. 2018 mBio Discussion HIV I124A;P122A 140;130 145;135 Gag 87 90 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Interestingly, a previous study demonstrated that T58I enhances CA-NC assembly in vitro. 2018 mBio Discussion HIV T58I 50 54 NC;Capsid 67;64 69;66 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Interestingly, there does appear to be some cross talk between the PPIP(122-125) motif and SP1, as a mutation at residue 8 of SP1 (SP1-T8I) results in conformational changes in the PPIP(122-125) loop. 2018 mBio Discussion HIV T8I 135 138 SP1;SP1;SP1 91;126;131 94;129;134 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. It is possible that the requisite number of CA subunits is not generated in P122A or I124A particles. 2018 mBio Discussion HIV I124A;P122A 85;76 90;81 Capsid 44 46 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. Sequential propagation of the P122A and I124A mutants in the MT-4 and Jurkat T-cell lines led to the emergence of escape mutants containing second-site changes within the CA-NTD. 2018 mBio Discussion HIV I124A;P122A 40;30 45;35 Capsid 171 173 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. T58A improved replication capacity only for I124A virus, but the addition of V11I was required to fully rescue replication kinetics of both T58A/P122A and T58A/I124A mutants. 2018 mBio Discussion HIV I124A;I124A;P122A;T58A;T58A;V11I;T58A 44;160;145;140;155;77;0 49;165;150;144;159;81;4 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. The P122A and I124A mutants both produce virions with a disordered Gag lattice and a wider size distribution than the WT. 2018 mBio Discussion HIV I124A;P122A 14;4 19;9 Gag 67 70 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. These three models are not mutually exclusive; the combination of conformational changes in CA, lower levels of mature CA, and higher levels of CA-SP1 in P122A and I124A virions could act in concert to prevent conical core formation. 2018 mBio Discussion HIV I124A;P122A 164;154 169;159 SP1;Capsid;Capsid;Capsid 147;92;119;144 150;94;121;146 30327442 Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation. V11I alone did not rescue the replication ability of either P122A or I124A. 2018 mBio Discussion HIV I124A;P122A;V11I 69;60;0 74;65;4 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. In Guinea Bissau, the most commonly used NNRTI is Efavirenz which is less effective in patients with the mutation K103N/S. 2018 PloS one Discussion HIV K103N;K103S 114;114 121;121 NNRTI 41 46 30379960 Prevalence of HIV-1 pretreatment drug resistance among treatment naive pregnant women in Bissau, Guinea Bissau. The K103N/S mutation/s was found most frequently in this study and represents one of the most commonly detected pretreatment DR mutations in most LMIC since ART roll out. 2018 PloS one Discussion HIV K103N;K103S 4;4 11;11 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Finally, while the tenofovir-selected mutation K65R confers significant resistance to tenofovir and abacavir, its combination with M184IV actually increases the level of resistance to abacavir, but decreases resistance to tenofovir. 2019 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184I;M184V 47;131;131 51;137;137 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Furthermore, subtype-specific differential resistance profiles/propensities must be taken into account, such as the higher prevalence of K65R in subtype C virological failures. 2019 The Journal of antimicrobial chemotherapy Discussion HIV K65R 137 141 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Moreover, the detection of TAMs, likely resulting from prior use of TAs, can enhance the resistance to abacavir in the presence of M184V whilst susceptibility to tenofovir might be increased. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184V 131 136 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Significant additional mutations, including K65R, were observed at the 5% level, but not the 20% level, suggesting NGS might be useful in treatment-experienced patients. 2019 The Journal of antimicrobial chemotherapy Discussion HIV K65R 44 48 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. The higher, but non-statistically significant, level of resistance to abacavir compared with tenofovir in the context of use of an FDC containing tenofovir/emtricitabine/efavirenz in this population might be explained by the high prevalence of the M184IV mutations, selected early in regimen failure by cytosine analogues, which can also confer partial resistance to abacavir. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 248;248 254;254 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. We did observe Q148R, which is associated with high-level dolutegravir resistance when accompanied by the G140S/A mutations. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G140A;G140S;Q148R 106;106;15 113;113;20 30380053 Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. We found a low level of resistance to zidovudine among both ART initiators and ART-exposed participants despite the detection of TAMs; this is explained by the fact that most of the TAMs were associated with M184V and/or K65R, mutations known to increase susceptibility to zidovudine. 2019 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184V 221;208 225;213 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. A high proportion of TDR was found in subtype A as a result of one German MSM transmission network spreading the PI resistance mutation M46I. 2018 PloS one Discussion HIV M46I 136 140 PI 113 115 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Along these lines, increasing proportions of NNRTI resistance and particularly of the K103N mutation were also reported from MSM networks in Greece and in San Diego. 2018 PloS one Discussion HIV K103N 86 91 NNRTI 45 50 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Although phylogenetic analysis revealed that there was no significant spread of K103N within one or more active transmission networks (as shown for the PI mutations among MSM) we assume that these phylogenetic unrelated K103N carrying strains are a result of continuous onwards transmission of the persisting K103N mutation among long term as well as recent infected individuals and therefore, are not appearing as a coherent transmission network in our phylogenetic analysis. 2018 PloS one Discussion HIV K103N;K103N;K103N 80;220;309 85;225;314 PI 152 154 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Large transmission networks of German MSM were observed for the most frequently transmitted NRTI mutation T215S (revertant of T215Y/F), and the PI resistance mutations M46I and V82L. 2018 PloS one Discussion HIV M46I;T215F;T215S;T215Y;V82L 168;126;106;126;177 172;133;111;133;181 NRTI;PI 92;144 96;146 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. On the other hand, NNRTI resistance is underestimated due to the lack of the E138A mutation. 2018 PloS one Discussion HIV E138A 77 82 NNRTI 19 24 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Secondly, the increasing trend of K103N infections in MSM, individuals of German origin and with subtype B infection (Fig 4A) might be explained by the fact that German MSM are known to have the highest rates of recent infections because they test more frequently than other transmission groups. 2018 PloS one Discussion HIV K103N 34 39 HIV infections 97 116 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. So far, resistance mutations selected by tenofovir and emtricitabine (K65R, K70R and M184V) have been rare (below 1%). 2018 PloS one Discussion HIV K65R;K70R;M184V 70;76;85 74;80;90 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. The proportion of transmitted PI resistance was higher in Germany (3.2%) than in other European countries (2.0%), presumably due to large clusters of the M46I and V82L mutations. 2018 PloS one Discussion HIV M46I;V82L 154;163 158;167 PI 30 32 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Therefore, 'de novo' selection of K103N mutations in Germany followed by transmission to newly diagnosed persons seems to be unlikely in times of highly suppressive cART and pre-treatment resistance testing. 2018 PloS one Discussion HIV K103N 34 39 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Therefore, the predicted resistance to the currently recommended first-line regimens consisting of two NRTI plus one PI or one INSTI is very low at the population level (<2.3%) while primary resistance to NNRTI is frequent with 9.1%: 4.9% to efavirence (due to the K103N mutation) and 6.0% to rilpivirine (due to the frequent E138A polymorphism). 2018 PloS one Discussion HIV E138A;K103N 326;265 331;270 INSTI;NNRTI;NRTI;PI 127;205;103;117 132;210;107;119 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. Therefore, we assume that the increase of the K103N mutation in our study population is the result of two developments: firstly, the import of the K103N mutation with non-B subtypes from abroad appears to have occurred at quite low levels (Fig 4B). 2018 PloS one Discussion HIV K103N;K103N 46;147 51;152 30408827 Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. This increase was mainly driven by the K103N mutation selected by the first generation NNRTIs nevirapine and efavirenz. 2018 PloS one Discussion HIV K103N 39 44 NNRTI 87 93 30409215 Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay. The kind, number, and frequency of the minority drug resistance mutations identified matched the cART history of the patients, the most common being M46I/L and I50 V (PIs), K65R, D67 N, L74I, M184 V/I, and K219Q (NRTIs), and L100I (NNRTIs). 2018 AIDS research and therapy Discussion HIV D67N;I50V;K219Q;K65R;L100I;L74I;M184I;M184V;M46I;M46L 179;160;206;173;225;186;192;192;149;149 184;165;211;177;230;190;200;200;155;155 NNRTI;NRTI;PI 232;213;167 238;218;170 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. found that one patient newly acquired M184 V resistance mutations after 96 weeks second-line ART. 2018 BMC infectious diseases Discussion HIV M184V 38 44 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. However, K65R was not detected in other patients after switching to second-line ART, which was consistent with Boyd et al. 2018 BMC infectious diseases Discussion HIV K65R 9 13 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. In our study, K65R was detected in four patients at baseline, which may be related to drugs used in the first-line ART; these four patients achieved viral suppression during second-line treatment. 2018 BMC infectious diseases Discussion HIV K65R 14 18 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. show that TAM (M41 L, L210 W, and T215F/Y) and M184I/V mutations related to NRTI drug resistance increased after patients switched to the second-line regimen. 2018 BMC infectious diseases Discussion HIV L210W;M184I;M184V;M41L;T215F;T215Y 22;47;47;15;34;34 28;54;54;20;41;41 NRTI 76 80 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. Some reports indicate that the NRTI resistance mutation, M184 V, can enhance viral sensitivity to TDF, which could result in effective virus suppression. 2018 BMC infectious diseases Discussion HIV M184V 57 63 NRTI 31 35 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. TDF was used in the second-line program; the mutations associated with resistance to TDF were K65R, TAM (M41 L, K70R, L210 W, T215F), D67N, K70E, and Y115F. 2018 BMC infectious diseases Discussion HIV D67N;K65R;K70E;K70R;L210W;M41L;T215F;Y115F 134;94;140;112;118;105;126;150 138;98;144;116;124;110;131;155 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. The D67N mutation, present with other TAMs, can result in reduced susceptibility to TDF. 2018 BMC infectious diseases Discussion HIV D67N 4 8 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. The K65R mutation causes intermediate/high-level resistance to TDF; use of TAMs (M41 L, K70R, L210 W, T215F) can reduce TDF susceptibility and cause intermediate/low level resistance to TDF. 2018 BMC infectious diseases Discussion HIV K65R;K70R;L210W;M41L;T215F 4;88;94;81;102 8;92;100;86;107 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. The K70E and Y115F mutations cause low-level resistance to TDF as well. 2018 BMC infectious diseases Discussion HIV K70E;Y115F 4;13 8;18 30442114 Research on the treatment effects and drug resistances of long-term second-line antiretroviral therapy among HIV-infected patients from Henan Province in China. The M184 V/I mutation was detected in nine patients after switching to second-line therapy, which can attributed to the use of 3TC in the program. 2018 BMC infectious diseases Discussion HIV M184I;M184V 4;4 12;12 30477526 Long-term virological outcome in children receiving first-line antiretroviral therapy. Among those who developed VF, M184V, K103N, and Y181C were the most common DRMs observed as in South Africa. 2018 AIDS research and therapy Discussion HIV K103N;M184V;Y181C 37;30;48 42;35;53 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. Among 1943 individuals living with HIV in San Francisco who had at least one sequence reported to HIV surveillance from 2013-2017, 356 (18.3%) had an M184V mutation detected in at least one genotype, of whom 62 were not virally suppressed based on their most recent viral load (Personal communication, Mia Chen, SFDPH HIV surveillance, July 2, 2018). 2018 The lancet. HIV Discussion HIV M184V 150 155 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. In San Francisco from 2014-2016, of 338 genotypes from individuals newly diagnosed with HIV, only three (0.89%) had a transmitted M184V mutation. 2018 The lancet. HIV Discussion HIV M184V 130 135 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. In the U.S., approximately 0.4-1.05% of persons newly diagnosed with HIV have a virus with a transmitted M184V mutation. 2018 The lancet. HIV Discussion HIV M184V 105 110 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. Of the six reported cases, five of the acquired viral strains had the M184V mutation in RT (Table 1), leading to high-level resistance to FTC. 2018 The lancet. HIV Discussion HIV M184V 70 75 RT 88 90 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. The prevalence of people living with HIV who have both a detectable VL and an M184V mutation will vary from jurisdiction to jurisdiction. 2018 The lancet. HIV Discussion HIV M184V 78 83 30503324 Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. Thus up to 62/1943 (3%) of individuals in San Francisco with HIV have both a virus with an M184V mutation and a detectable viral load, and could potentially transmit HIV to a partner on PrEP. 2018 The lancet. HIV Discussion HIV M184V 91 96 30513108 Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial. Despite similar rates of virological failure >=1,000 copies/mL, raltegravir-intensified ART was associated with lower rates of the NRTI mutation K219E/Q and the NNRTI mutations K101E/P and P225H. 2018 PLoS medicine Discussion HIV K101E;K101P;K219E;K219Q;P225H 177;177;145;145;189 184;184;152;152;194 NNRTI;NRTI 161;131 166;135 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. A similar but distinct flap rearrangement was previously observed in response to a coevolution mutation in Gag substrate in the I50V/A71V variant, which enhances vdW interactions with the substrate. 2019 ACS infectious diseases Discussion HIV A71V;I50V 133;128 137;132 Gag 107 110 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. As intended, the bulkier P1' moiety of UMass6 helped to retain better potency against I84V, but the reverse was the case for I50V mutation. 2019 ACS infectious diseases Discussion HIV I50V;I84V 125;86 129;90 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. However, groups larger than that in UMass1 may act as a selective pressure forcing I50V to become a dominant variant. 2019 ACS infectious diseases Discussion HIV I50V 83 87 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Our results validated that larger P1' moieties were effective against I84V and V82I mutations, but an unexpected alternative mechanism of resistance was uncovered against the I50V mutation. 2019 ACS infectious diseases Discussion HIV I50V;I84V;V82I 175;70;79 179;74;83 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Rather than a simple alteration in interactions at this subsite, there was an overall and asymmetric rearrangement of the vdW interactions throughout the active site pocket due to either I84V or I50V mutation. 2019 ACS infectious diseases Discussion HIV I50V;I84V 195;187 199;191 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. The I50V mutation is commonly observed in variants that are resistant to DRV, and has previously been investigated. 2019 ACS infectious diseases Discussion HIV I50V 4 8 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Thus, although both I84V and I50V are primary resistance mutations with the same side chain change in the S1' pocket, the interplay between P1' moiety and rearrangements of inhibitor interactions were distinct, and moreover contrasting for these two mutations. 2019 ACS infectious diseases Discussion HIV I50V;I84V 29;20 33;24 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Thus, the bulkier P1' groups in UMass inhibitors might cause hyper-susceptibility to V82I and prevent selection of this mutation on resistance pathways. 2019 ACS infectious diseases Discussion HIV V82I 85 89 30543749 Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. Unlike the other two mutations, V82I did not confer measurable resistance against the inhibitors tested. 2019 ACS infectious diseases Discussion HIV V82I 32 36 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. Emergence of T215Y and T215F from the WT virus. 2019 The Journal of antimicrobial chemotherapy Discussion HIV T215F;T215Y 23;13 28;18 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. In support of the former hypothesis, deep sequencing in an ART-naive Belgian population with T215rev failed to identify T215Y, T215F or other NRTI mutations. 2019 The Journal of antimicrobial chemotherapy Discussion HIV T215F;T215Y 127;120 132;125 NRTI 142 146 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. In this epidemiological context, T215rev variants do not necessarily indicate the transmission of T215Y/T215F, thus diminishing clinical significance. 2019 The Journal of antimicrobial chemotherapy Discussion HIV T215F;T215Y 104;98 109;103 30544247 Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. T215rev variants are molecular intermediates in reverse transition between T215Y or T215F and WT, and are generally taken to signal persistence of progenitor T215Y/T215F. 2019 The Journal of antimicrobial chemotherapy Discussion HIV T215F;T215F;T215Y;T215Y 84;164;75;158 89;169;80;163 30557314 The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. The structure of Env is important in vaccine studies: accordingly, the antigen in this study was stabilised by replacing the furin cleavage site with a flexible glycine-rich linker, and a I559P mutation. 2018 PloS one Discussion HIV I559P 188 193 Env 17 20 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. Indeed, all our observed K103N mutations formed two phylogenetically related transmission clusters spanning over several years, suggesting that they may have been in circulation for a while, and were unsuspectingly propagated onward in the community as new infections. 2018 PloS one Discussion HIV K103N 25 30 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. Observed TDR mutations were non-complex, with a predominance of the common NNRTI-based K103N mutation. 2018 PloS one Discussion HIV K103N 87 92 NNRTI 75 80 30562356 HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya. The high level of K103N mutation is consistent with literature from Kenya, and has been attributed to the widespread use of NNRTI in first line ART and the historic use of Nevirapine monotherapy in the prevention of mother to child transmission. 2018 PloS one Discussion HIV K103N 18 23 NNRTI 124 129 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Although selected by DTG in RAL- or EVG-experienced individuals, there are limited data on the impact of the sole emergence of T97A to DTG in the presence of other INSTI-associated resistence mutations in B or non-B subtypes. 2018 Open forum infectious diseases Discussion HIV T97A 127 131 INSTI 164 169 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Data from our 2 participants suggest that the single emergence of T97A in HIV with preexisting major integrase DRMs may be rapid and lead to more profound reduction in DTG antiviral activity. 2018 Open forum infectious diseases Discussion HIV T97A 66 70 IN 101 110 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. DTG represents a strong antiretroviral choice, but our experience with these 2 individuals suggests that the emergence of T97A in HIV with preexisting major integrase DRMs may be relatively rapid and lead to profound reduction in antiviral activity of DTG. 2018 Open forum infectious diseases Discussion HIV T97A 122 126 IN 157 166 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Emergence of the T97A mutation leading to reduced susceptibility to DTG in INSTI-experienced individuals was first reported in the VIKING trials. 2018 Open forum infectious diseases Discussion HIV T97A 17 21 INSTI 75 80 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Here we describe emergence of T97A in 2 heavily treatment-experienced individuals within 8-24 weeks of receiving DTG-containing salvage therapy, which was accompanied by a >10-fold increase in IC50 to DTG. 2018 Open forum infectious diseases Discussion HIV T97A 30 34 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. In an analysis of individual derived isolates with E138K, G140S, and Q148H, the FC to bictegravir is reported to be as high as 19-fold (2-19), whereas baseline DTG FC was 63 (3-63). 2018 Open forum infectious diseases Discussion HIV E138K;G140S;Q148H 51;58;69 56;63;74 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. In both individuals, NGS did not detect T97A before DTG therapy, but the mutation was readily detectable (NGS, in >=95% of sample) within weeks of starting or restarting DTG. 2018 Open forum infectious diseases Discussion HIV T97A 40 44 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. In site-directed mutagenesis studies, T97A alone has minimal impact on INSTI susceptibility or HIV replication capacity. 2018 Open forum infectious diseases Discussion HIV T97A 38 42 INSTI 71 76 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. In the VIKING phase IIb trial, 2 subjects received twice-daily DTG after DTG functional monotherapy and subsequently developed the T97A mutation. 2018 Open forum infectious diseases Discussion HIV T97A 131 135 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. In these cases, genotypic analysis revealed that T97A emerged in addition to other mutations, including E92E/Q, E138E/K, and N155H. 2018 Open forum infectious diseases Discussion HIV E138E;E138K;E92E;E92Q;N155H;T97A 112;112;104;104;125;49 119;119;110;110;130;53 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. In VIKING-4, 2 subjects with baseline integrase substitutions at positions 140 and 148 developed T97A as the only new INSTI-associated DRM. 2018 Open forum infectious diseases Discussion HIV T97A 97 101 IN;INSTI 38;118 47;123 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Individuals developed high-level resistance within 4-24 weeks of DTG, and T97A was usually accompanied by additional mutations. 2018 Open forum infectious diseases Discussion HIV T97A 74 78 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. It is likely the once-daily DTG, rather than recommended twice-daily, may have contributed to the emergence of the T97A mutation, which highlights the importance of ensuring appropriate dosing for highly treatment-experienced patients receiving DTG as part of salvage therapy. 2018 Open forum infectious diseases Discussion HIV T97A 115 119 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. It is possible that these VIKING participants developed T97A quickly but it was not detected until after they had acquired additional mutations. 2018 Open forum infectious diseases Discussion HIV T97A 56 60 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Of 3881 individuals enrolled across 16 clinical trials, the T97A mutation emerged alone in 8 individuals (EVG, n = 6; RAL, n = 2) who were treatment experienced, without primary INSTI-associated DRMs and after at least a year on therapy. 2018 Open forum infectious diseases Discussion HIV T97A 60 64 INSTI 178 183 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Participant #2 developed the T97A mutation while on a suboptimal regimen including once-daily DTG/ABC/3TC and tenofovir DF. 2018 Open forum infectious diseases Discussion HIV T97A 29 33 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Several INSTIs under development retain potent in vitro antiviral activity against mutations at positions N155, G140, Q148, and T97A, and may show promise as candidates for drug development. 2018 Open forum infectious diseases Discussion HIV T97A 128 132 INSTI 8 14 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. T97A emerged at week 32 (DTG FC 55) and day 28 (DTG FC 32). 2018 Open forum infectious diseases Discussion HIV T97A 0 4 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. T97A has also been reported in pooled clinical trial data of RAL and EVG from ARV-naive and INSTI-naive ARV-experienced individuals. 2018 Open forum infectious diseases Discussion HIV T97A 0 4 INSTI 92 97 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. T97A is infrequently present (1%-5%) in INSTI-naive individuals, though it is reported at a higher rate in HIV-1 subtypes A, J, and P. 2018 Open forum infectious diseases Discussion HIV T97A 0 4 INSTI 40 45 30568974 Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. The observed increases in DTG FC were higher in our 2 participants (66 and 119, respectively) after the sole emergence of T97A compared with reported increases in DTG FC in the VIKING trials. 2018 Open forum infectious diseases Discussion HIV T97A 122 126 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. A competitive relationship among drug-resistant strains during long-term antiviral treatment (especially with NNRTIs) exists due to the presence of Y181C/I/V and K103 N/R/S, which affect the binding of NNRTIs to the active sites of the enzymes. 2019 Virology journal Discussion HIV K103N;K103R;Y181C;Y181I;Y181V 162;162;148;148;148 172;172;157;157;157 NNRTI;NNRTI 110;202 116;208 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. Another study showed that when 3TC was used as a single drug, M184 V/I resistant strains replaced wild strains in a few weeks and that when 3TC was used in combination treatments, M184 V/I DR strains always appeared first. 2019 Virology journal Discussion HIV M184I;M184I;M184V;M184V 62;180;62;180 70;188;70;188 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. In this study, the occurrence rates for K103 N/R/S, G190A, and V106A were higher than that for Y181C/I/V; however, after a long period, the Y181C/I/V and K103 N/R/S mutations showed a greater prevalence. 2019 Virology journal Discussion HIV G190A;K103N;K103N;K103R;K103R;V106A;Y181C;Y181C;Y181I;Y181I;Y181V;Y181V 52;40;154;40;154;63;95;140;95;140;95;140 57;50;164;50;164;68;104;149;104;149;104;149 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. L10 V/F/I had the highest rate (up to 6.82%). 2019 Virology journal Discussion HIV L10V 0 9 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. M184 V/I was the most frequent NRTI mutation found during the first and second analyses. 2019 Virology journal Discussion HIV M184V 0 8 NRTI 31 35 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. Mutation at sites such as M184 V/I and K103 N are important because they cause resistance to several drugs, and thus, play a decisive role in the extent to which DR changes over time. 2019 Virology journal Discussion HIV K103N;M184I;M184V 39;26;26 45;34;34 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. Previous studies have performed adaptive sequencing of subjects receiving NNRTIs, and confirmed that the most common mutations are as follows: Y181C/I/V > K103 N/R/S > G190A > V106A. 2019 Virology journal Discussion HIV G190A;K103N;K103R;V106A;Y181C;Y181I;Y181V 168;155;155;176;143;143;143 173;165;165;181;152;152;152 NNRTI 74 80 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. This may explain the high resistance caused by and the incidence of the M184 V/I mutation observed in this study when 3TC was used. 2019 Virology journal Discussion HIV M184I;M184V 72;72 80;80 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. Two clusters were studied here; TAM-1 (M41 L and T215Y) and TAM-2 (D67N, K70R, and K219Q). 2019 Virology journal Discussion HIV D67N;K219Q;K70R;M41L;T215Y 67;83;73;39;49 71;88;77;45;54 30621727 Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China. We observed that NNRTI mutations principally occurred in the first and second periods of treatment failure and were mainly K103 N/R/S, V179D/E, Y181C/I/V, G190A, Y188L/C. 2019 Virology journal Discussion HIV G190A;K103N;K103R;V179D;V179E;Y181C;Y181I;Y181V;Y188C;Y188L 155;123;123;135;135;144;144;144;162;162 160;133;133;142;142;153;153;153;169;169 NNRTI 17 22 30648124 Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance. We report occurrence of the R263K integrase mutation 18 months into treatment with DTG in the context of vertically acquired subtype D infection. 2019 Open forum infectious diseases Discussion HIV R263K 28 33 IN 34 43 HIV infections 125 144 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. Although we could not obtain a Kaplan-Meier estimate for the mutation F77L, we did observe the mutation for 10.2 years in one study patient, the longest follow-up time for any TDRM in our cohort. 2019 PloS one Discussion HIV F77L 70 74 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. An extended time between sampling can lead to an overestimation of the mean survival time, especially for mutations with short persistence as we have proposed for M184V. 2019 PloS one Discussion HIV M184V 163 168 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. As the combination of RPV, FTC and TDF is approved as a single-tablet regimen (Eviplera), with RPV selecting for E138 mutations and FTC selecting for the M184I mutation, the emergence of E138 mutations, especially in combination with M184I, has to be monitored more closely in the future. 2019 PloS one Discussion HIV M184I;M184I 154;234 159;239 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. Competition experiments have shown that E138A/G are the substitutions with the highest fitness, followed by E138R/K/Q, which is in line with the long mean persistence times found in our study. 2019 PloS one Discussion HIV E138A;E138G;E138K;E138Q;E138R 40;40;108;108;108 47;47;117;117;117 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. D67N has been shown in other studies to persist for a long time, while K70R has been shown to be lost rather quickly. 2019 PloS one Discussion HIV K70R;D67N 71;0 75;4 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. For the NNRTI RPV recommended for first-line regimens, the baseline susceptibility was predicted to be reduced in our study cohort, mainly due to the NNRTI-associated polymorphic resistance mutations E138A/G/K/R. 2019 PloS one Discussion HIV E138A;E138G;E138K;E138R 200;200;200;200 211;211;211;211 NNRTI;NNRTI 8;150 13;155 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. However, the long persistence of K70R in our study was observed in a patient without additional TDRMs. 2019 PloS one Discussion HIV K70R 33 37 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. In concordance with the three other studies on the persistence of TDRMs, for most PI mutations (I54V, K43T, L23I, M46I/L/V) a long mean survival time between 2.2 and 4.2 years was found in our study cohort, with the exception of K20T that had a mean survival time of one (95% CI 0.4-1.2) year. 2019 PloS one Discussion HIV I54V;K20T;K43T;L23I;M46I;M46L;M46V 96;229;102;108;114;114;114 100;233;106;112;122;122;122 PI 82 84 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. In contrast, the mean survival times determined for NRTI mutations T215Y/A/N and L74I, which were also found at a lower proportion among the transmitted NRTI mutations, ranged from 1.0 to 1.7 years. 2019 PloS one Discussion HIV L74I;T215A;T215N;T215Y 81;67;67;67 85;76;76;76 NRTI;NRTI 52;153 56;157 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. In our study cohort, the NRTI mutations M41L, L210W, T215C/D/S and K219R, which also occurred in high frequencies among the transmitted NRTI mutations, had calculated mean survival times of between 2.9 and 6.4 years. 2019 PloS one Discussion HIV K219R;L210W;M41L;T215C;T215D;T215S 67;46;40;53;53;53 72;51;44;62;62;62 NRTI;NRTI 25;136 29;140 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. Indeed, among the NNRTI mutations transmitted, the mutations K103N and G190A also showed long mean survival times of 5.3 (95% CI 4.2-6.5) and 3.8 years (95% CI 2.8-4.8), respectively, which agrees with the results from the three other cohort studies. 2019 PloS one Discussion HIV G190A;K103N 71;61 76;66 NNRTI 18 23 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. It has been shown in vitro that the fitness cost of K70R is higher in combination with other mutations, possibly explaining its faster reversion in other in vivo cohort studies. 2019 PloS one Discussion HIV K70R 52 56 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. It has recently been shown that the mutations E138K and M184I can mutually compensate for each other, resulting in restoration of viral replication capacity. 2019 PloS one Discussion HIV E138K;M184I 46;56 51;61 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. Moreover, the mutations K70R and D67N were observed in one study patient each for 6.9 and 5.9 years, respectively. 2019 PloS one Discussion HIV D67N;K70R 33;24 37;28 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. One exception was the long mean persistence time of 3.2 years (95% CI 1.9-5.4) of the M184V mutation in our study population, which is in contrast to the rapid loss observed in all other in vivo persistence studies. 2019 PloS one Discussion HIV M184V 86 91 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The K103N mutation, causing high resistance to the first generation NNRTI drugs NVP and EFV that are recommended for second-line regimens in Europe, was also frequently observed in our study cohort. 2019 PloS one Discussion HIV K103N 4 9 NNRTI 68 73 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The longest mean survival times of approximately 8 years were observed for the NNRTI mutations E138A/G/K. 2019 PloS one Discussion HIV E138A;E138G;E138K 95;95;95 104;104;104 NNRTI 79 84 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. The most likely reason is that one study patient was included who lost the M184V mutation during an interval of 3.1 years between two plasma samplings. 2019 PloS one Discussion HIV M184V 75 80 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. This might also be the case for mutations E138A, M46I, M46V and T215S, because for these TDRMs there was a period of more than 2.5 years between samples collected with and without the corresponding mutation. 2019 PloS one Discussion HIV E138A;M46I;M46V;T215S 42;49;55;64 47;53;59;69 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. We could not obtain a Kaplan-Meier estimate for L90M, but persistence of L90M was observed in one study patient followed for 8.4 years. 2019 PloS one Discussion HIV L90M;L90M 48;73 52;77 30650082 Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. who observed persistence of L90M for up to 5.1 years. 2019 PloS one Discussion HIV L90M 28 32 30714528 Molecular Antiretroviral Resistance Markers of Human Immunodeficiency Virus-1 of CRF01_AE Subtype in Bali, Indonesia. Molecular marker mutations in more than 50% of treatment failure patients were M184V, T215A/Y/F, D67N/G, and M41L. 2018 Current HIV research Discussion HIV D67G;D67N;M184V;M41L;T215A;T215F;T215Y 97;97;79;109;86;86;86 103;103;84;113;95;95;95 30714528 Molecular Antiretroviral Resistance Markers of Human Immunodeficiency Virus-1 of CRF01_AE Subtype in Bali, Indonesia. Molecular markers of TAMs, M184V (100%), T215A/Y/F (88.2%), D67N/G (76.5%), and M41L (58.8%), were found in more than 50% of treatment failure patients. 2018 Current HIV research Discussion HIV D67G;D67N;M184V;M41L;T215A;T215F;T215Y 60;60;27;80;41;41;41 66;66;32;84;50;50;50 30714528 Molecular Antiretroviral Resistance Markers of Human Immunodeficiency Virus-1 of CRF01_AE Subtype in Bali, Indonesia. The pattern of resistance-associated mutations found in this study differs to that found in Maumere, East Nusa Tenggara, except for M184V. 2018 Current HIV research Discussion HIV M184V 132 137 30714528 Molecular Antiretroviral Resistance Markers of Human Immunodeficiency Virus-1 of CRF01_AE Subtype in Bali, Indonesia. There are two clusters of TAMs; cluster 1 includes substitutions of M41L, L210W and T215Y, while cluster 2 of D67N, K70R, T125F and K219Q/E/N. 2018 Current HIV research Discussion HIV D67N;K219E;K219N;K219Q;K70R;L210W;M41L;T125F;T215Y 110;132;132;132;116;74;68;122;84 114;141;141;141;120;79;72;127;89 30732150 Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana. Major drug resistance mutations M184V, K65R, and Y115F were detected in an ART-experienced patient. 2019 Medicine Discussion HIV K65R;M184V;Y115F 39;32;49 43;37;54 30732150 Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana. The K65R and Q151M substitutions are known to occur more commonly in HIV-2 than in HIV-1 infections, and often appear together with M184V in patients that receive NRTI, as shown in an ART-experienced patient in this study. 2019 Medicine Discussion HIV K65R;M184V;Q151M 4;132;13 8;137;18 NRTI 163 167 HIV infections 83 99 30732150 Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana. The occurrence of Y115F, abacavir-induced mutation, together with M184V, which reduces the susceptibility of lamivudine (3TC), emtricitabine, and abacavir confers possible resistance to the drugs in the NRTIs class. 2019 Medicine Discussion HIV M184V;Y115F 66;18 71;23 NRTI 203 208 30732150 Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana. The presence of K65R is indicative of class-wide nucleoside analogue resistance. 2019 Medicine Discussion HIV K65R 16 20 30732150 Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana. The presence of NRTI mutations M184V, K65R, and Y115F found in an ART-experienced person in this study confirms the emergence of ART resistance to the currently available antiretroviral drugs under drug pressure. 2019 Medicine Discussion HIV K65R;M184V;Y115F 38;31;48 42;36;53 NRTI 16 20 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. Although the rMVA used in this study contained the K1L vaccinia virus host range gene, which makes the virus replication competent in RK13 cells, it did not appear to result in replication in the rabbits, as evidenced by the monitoring of the weight and well-being of the animals. 2019 Journal of virology Discussion HIV K1L 51 54 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. It is not known if the inclusion of K1L would affect immunogenicity of MVA. 2019 Journal of virology Discussion HIV K1L 36 39 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. The flexible linker and I559P mutation used in our vaccines should prevent the dissociation of the gp120 and gp41 subunits and better stabilize the Env trimer, consequently leading to improved antibody responses. 2019 Journal of virology Discussion HIV I559P 24 29 gp120;gp41;Env 99;109;148 104;113;151 30760570 Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. To the best of our knowledge, this is the first time DNA and MVA vaccines expressing a gp150 HIV-1 envelope protein containing a flexible glycine linker and I559P mutation have been utilized. 2019 Journal of virology Discussion HIV I559P 157 162 Env 99 107 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. Although M184V/I was not reported at this time, it was possible that this mutation was archived. 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV M184I;M184V 9;9 16;16 30798679 HIV Viral Rebound Due to a Possible Drug-Drug Interaction between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Calcium-Containing Products: Report of 2 Cases. Once E/C/F/TAF was initiated, M184V/I may have reemerged, causing resistance to emtricitabine. 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV M184I;M184V 30;30 37;37 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. C9007A also results in a one-amino-acid truncation of Nef, but an exhaustive search of the literature failed to find a description of an important biological property for the terminal cysteine in Nef or to indicate that its loss would have an impact on Nef function. 2019 mBio Discussion HIV C9007A 0 6 Nef;Nef;Nef 54;196;253 57;199;256 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. Considering the location of the mutations in the context of previously published work, the Vpr null mutation and the C9007A transversion may contribute to high-level resistance to the Vif antagonists used here. 2019 mBio Discussion HIV C9007A 117 123 Vif;Vpr 184;91 187;94 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. The C9007A transversion in the distal region of the LTR promoter suggests that the mutation could elevate proviral transcriptional activity. 2019 mBio Discussion HIV C9007A 4 10 LTR 52 55 30808702 HIV-1 Escape from Small-Molecule Antagonism of Vif. The complete genome of the cloned inhibitor-resistant virus was sequenced, and several mutations, in addition to the Vif V142I, were identified. 2019 mBio Discussion HIV V142I 121 126 Vif 117 120 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. 2) and R57G (data not shown) - significantly decreased Tat CPP uptake. 2019 Scientific reports Discussion HIV R57G 7 11 Tat 55 58 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Confocal microscopy with fluorescently labeled peptides showed that the presence of an arginine residue at position 57 is required for optimal uptake by cells because, both the substitutions - R57S. 2019 Scientific reports Discussion HIV R57S 193 197 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Furthermore, S57R substitution in a HIV-1C Tat protein reciprocally increased the uptake efficiency of Tat-C protein, transcriptional transactivation and subsequent neuroinflammation. 2019 Scientific reports Discussion HIV S57R 13 17 Tat;Tat 43;103 46;106 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. However, three of the clades, A, C and G displayed either a R57S or a R57G substitution. 2019 Scientific reports Discussion HIV R57G;R57S 70;60 74;64 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. In our studies, we focused on R57S and excluded R57G substitution for the following reasons: (i) R57 and S57 residues are present in clade B & D or clade C respectively - which represent important, well-studied clades; (ii) as a proof of principle, we wanted to compare two residues R and S at position 57; (iii) much is known about the neuropathogenesis of clades HIV-1 B (which mainly has Arg at this position) and HIV-1C (which mainly has Ser at this position; (iv) however, literature on the incidence and mechanisms of HIV-1 clade A or clade G -mediated neuropathology is sparse. 2019 Scientific reports Discussion HIV R57G;R57S 48;30 52;34 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. It is possible that the incidence of HAND in HIV-1C patients is associated with a neurovirulence signature that includes an S57R mutation in Tat. 2019 Scientific reports Discussion HIV S57R 124 128 Tat 141 144 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. We have reported a naturally occurring C31S polymorphism in Tat dicysteine motif in HIV-1C, which is considered to be important for monocyte chemotaxis function - a property that may underlie the increased monocyte infiltration in CNS that is a hallmark of HAD. 2019 Scientific reports Discussion HIV C31S 39 43 Tat 60 63 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. We propose that the R57S polymorphism has the potential to attenuate CNS neuroinflammation. 2019 Scientific reports Discussion HIV R57S 20 24 30824746 A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. When we treated human microglial cells with Tat variants, an R57S substitution reduced the transcriptional transactivation of several proinflammatory cytokine genes. 2019 Scientific reports Discussion HIV R57S 61 65 Tat 44 47 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. A major finding is that the double mutant Y88F/H547A completely attenuates the Tat-mediated inhibition of DAT reuptake function, which is consistent with our previous reports on Y88F- or H547A-induced attenuation of the Tat's effect. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F;Y88F 47;187;42;178 52;192;46;182 Tat;Tat 79;220 82;223 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Although including K92M mutation significantly decreases the Vmax for DA uptake in the triple mutant Y88F/K92M/H547A compared to Y88F/H547A, no significant change in the Bmax of [3H]WIN 35,428 binding is found in the double or triple mutants, suggesting that the multiple mutations may alter DAT re-uptake function rather than the substrate binding sites on DAT. 2019 Scientific reports Discussion HIV H547A;K92M;Y88F;H547A;K92M;Y88F 111;106;101;134;19;129 116;110;105;139;23;133 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. An allosteric modulatory mechanism may contribute to Y88F/H547A-mediated attenuation of Tat-induced inhibition of DA transport. 2019 Scientific reports Discussion HIV H547A;Y88F 58;53 63;57 Tat 88 91 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. As Y88 is spatially adjacent to R85 and K92 in helix TM1b, the double mutations on both Y88F and K92M are expected to induce more structural disturbance to the R85-D476 and K92-D313 salt brides, thus further decreasing Vmax of the transporter. 2019 Scientific reports Discussion HIV K92M;Y88F 97;88 101;92 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Double mutation of these residues preserves single mutant H547A-mediated enhancement of DA uptake and diminishes Tat-induced inhibition of DA transport. 2019 Scientific reports Discussion HIV H547A 58 63 Tat 113 116 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. First, compared with WT hDAT, Y88F/H547A enhances Vmax of DA uptake, whereas Y88F/K92M/H547A dramatically reduces the Vmax. 2019 Scientific reports Discussion HIV H547A;K92M;Y88F;H547A;Y88F 87;82;77;35;30 92;86;81;40;34 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. First, Y88F/H547A attenuates zinc-mediated increase in [3H]WIN35,428 binding relative to WT hDAT. 2019 Scientific reports Discussion HIV H547A;Y88F 12;7 17;11 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. For this reason, disrupting the K92-D313 salt bridge will likely impair or slow down the DA uptake process, which has been validated pharmacologically by mutations on K92 (K92M) and D313 (D313N). 2019 Scientific reports Discussion HIV D313N;K92M 188;172 193;176 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Furthermore, AMPH decreases the Vmax of DA uptake in both WT hDAT and Y88F/H547A, which is consistent with the previous report, however, the magnitude of the AMPH-mediated reduction of the Vmax in Y88F/H547A was greater than that in WT hDAT. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F;Y88F 75;202;70;197 80;207;74;201 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. H547 is expected to significantly affect the hDAT stability because H547 is adjacent to Y548 of the YYY motif, which is consistent with the observed increase in DA uptake by the H547A mutation. 2019 Scientific reports Discussion HIV H547A 178 183 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. However, AMPH-mediated DA efflux was reduced in H547A and Y88F/H547A, suggesting that mutations of Tyr88 and His547 residues alter the conformational equilibrium of the DAT transport transitions. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F 48;63;58 53;68;62 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. However, the inhibition potency of [3H]WIN35,428 binding for cocaine was decreased in Y88F/H547A but increased in Y88F. 2019 Scientific reports Discussion HIV H547A;Y88F;Y88F 91;86;114 96;90;118 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. However, Y88F increased the Km of DA binding by about 50%, suggesting that Y88F may slightly alter the local structure around Y88. 2019 Scientific reports Discussion HIV Y88F;Y88F 9;75 13;79 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. However, Y88F/H547A increased the DA uptake potency for cocaine and GBR12909, which is consistent with the single mutation of Y88F relative to WT hDAT. 2019 Scientific reports Discussion HIV H547A;Y88F;Y88F 14;9;126 19;13;130 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. In contrast, the combination of the mutated residues Y88, K92, and H547 does not follow a simple math addition, because compared to WT hDAT, a 96% reduction of Vmax was observed in Y88F/K92M/H547A, whereas the Vmax was decreased by 71% in K92M. 2019 Scientific reports Discussion HIV H547A;K92M;Y88F;K92M 191;186;181;239 196;190;185;243 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. In the current study, the double mutant Y88F/H547A retains the increased Vmax observed in H547A, suggesting a critical role of the mutated H547 residue in regulating transporter activity. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F 45;90;40 50;95;44 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Indeed, compared with WT hDAT, H547A, and Y88F/H547A enhances the Vmax values by 196% and 96%, respectively. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F 31;47;42 36;52;46 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Interestingly, the AMPH-mediated reduction of the Vmax was accompanied by increased Km values in WT hDAT but not Y88F/H547A. 2019 Scientific reports Discussion HIV H547A;Y88F 118;113 123;117 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Interestingly, the current study shows no difference in PMA-mediated reduction of DA uptake between Y88F/H547A and WT hDAT, indicating that Y88F/H547A-induced increase in Vmax is independent of PKC activity. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F;Y88F 105;145;100;140 110;150;104;144 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Our previous study has demonstrated that mutant H547A displays increased sensitivity to PKC-mediated downregulation of DAT function by PMA compared to WT hDAT. 2019 Scientific reports Discussion HIV H547A 48 53 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Our recent studies demonstrated that single hDAT mutants, Y88F, K92M, and H547A differentially regulate DAT reuptake but attenuate Tat's inhibitory effect on DAT function. 2019 Scientific reports Discussion HIV H547A;K92M;Y88F 74;64;58 79;68;62 Tat 131 134 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Second, consistent with the computational modeling prediction, Y88F/H547A attenuates Tat-induced inhibition of DA uptake observed in WT hDAT. 2019 Scientific reports Discussion HIV H547A;Y88F 68;63 73;67 Tat 85 88 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Second, Y88F/H547A augments basal DA efflux when compared to WT hDAT, which opposes our previous reports showing that neither Y88F nor H547A affected the basal efflux. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F;Y88F 13;135;8;126 18;140;12;130 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Similar to Y88F, Y88F/H547A displayed decreased potency for DA to inhibit [3H]WIN35,428 binding. 2019 Scientific reports Discussion HIV H547A;Y88F;Y88F 22;11;17 27;15;21 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Taken together, the results along with attenuated zinc-regulated [3H] WIN35,428 binding and increased basal DA efflux in Y88F/H547A further support that mutations of Tyr88 and His547 cause an alteration in conformational transitions, thereby disrupting the inhibitory effect of Tat on DAT reuptake function. 2019 Scientific reports Discussion HIV H547A;Y88F 126;121 131;125 Tat 278 281 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Taken together, Y88F/H547A, via an alteration of DAT conformational transitions, may influence the binding structure of hDAT-Tat complex, thereby disrupting Tat-induced inhibition of DA uptake. 2019 Scientific reports Discussion HIV H547A;Y88F 21;16 26;20 Tat;Tat 125;157 128;160 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. The current results indicate that the potency for AMPH inhibition of [3H]DA uptake was not altered in Y88F/H547A compared with WT hDAT, suggesting that the mutation of Tyr88 and His547 does not alter the interaction of AMPH with hDAT. 2019 Scientific reports Discussion HIV H547A;Y88F 107;102 112;106 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. The elevated basal DA efflux in Y88F/H547A may be attributed to its elevated Vmax of DA uptake and DA accumulation. 2019 Scientific reports Discussion HIV H547A;Y88F 37;32 42;36 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. The third finding is that Y88F/H547A displays an attenuation of zinc ion modulation of [3H]WIN35,428 binding, increased basal DAT-mediated DA efflux, and reduced AMPH-stimulated DA efflux. 2019 Scientific reports Discussion HIV H547A;Y88F 31;26 36;30 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Therefore, AMPH decreases DA transport but increases Km values in WT hDAT, whereas altered transporter conformation by Y88F/H547A may attenuate the increased Km. 2019 Scientific reports Discussion HIV H547A;Y88F 124;119 129;123 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Therefore, triple mutant Y88F/K92M/H547A has a lower Vmax compared to, single mutant K92M. 2019 Scientific reports Discussion HIV H547A;K92M;Y88F;K92M 35;30;25;85 40;34;29;89 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Therefore, we will investigate whether Y88F/H547A-induced increased DA uptake is dependent on palmitoylation activity. 2019 Scientific reports Discussion HIV H547A;Y88F 44;39 49;43 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. This conclusion is also supported by the increased Km in Y88F/H547A and no change in Km in Y88F/K92M/H547A. 2019 Scientific reports Discussion HIV H547A;K92M;Y88F;H547A;Y88F 101;96;91;62;57 106;100;95;67;61 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. This study sought to determine whether multiple mutations on these hDAT residues (Y88F/H547A) and (Y88F/K92M/H547A) influence the direct interactions between Tat and DAT. 2019 Scientific reports Discussion HIV H547A;K92M;Y88F;H547A;Y88F 109;104;99;87;82 114;108;103;92;86 Tat 158 161 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. We further determined the effect of double mutant Y88F/H547A on the basal DA uptake via hDAT and binding potency for DA, GBR12909, and cocaine. 2019 Scientific reports Discussion HIV H547A;Y88F 55;50 60;54 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Y88F/H547A had decreased the potency for [3H]DA to inhibit DA uptake relative to WT hDAT, which is similar to that in Y88F and H547A. 2019 Scientific reports Discussion HIV H547A;H547A;Y88F;Y88F 5;127;118;0 10;132;122;4 30846720 Mutational effects of human dopamine transporter at tyrosine88, lysine92, and histidine547 on basal and HIV-1 Tat-inhibited dopamine transport. Y88F/H547A, similar to Y88F, retained the [3H]WIN35,428 binding potency for GBR12909. 2019 Scientific reports Discussion HIV H547A;Y88F;Y88F 5;23;0 10;27;4 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. Among participants who had failed EFV+AZT+3TC with K103N in plasma RNA, 50% had detectable K103N in archival proviral DNA by Sanger sequencing for as long as 8 years after viral suppression with a PI-based regimen. 2019 Open forum infectious diseases Discussion HIV K103N;K103N 51;91 56;96 PI 197 199 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. In this study, deep sequencing, albeit of a limited number of proviruses, demonstrated an additional 21% of participants with minority levels of K103N. 2019 Open forum infectious diseases Discussion HIV K103N 145 150 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. In this study, we focused on the detection of the K103N mutation in proviral DNA, the drug-resistant mutation most frequently associated with virologic failure of EFV-based regimens. 2019 Open forum infectious diseases Discussion HIV K103N 50 55 30863788 Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens. The positive association between plasma HIV RNA level at viral failure and detection of K103N in proviral DNA is consistent with the maintenance of proviral DNA in PBMCs, the association between pre-ART plasma HIV RNA level and the on-ART level of proviral HIV DNA, and the well characterized persistence of K103N after discontinuation of NNRTI selection pressure. 2019 Open forum infectious diseases Discussion HIV K103N;K103N 88;308 93;313 NNRTI 339 344 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. In Turkey, the most frequent mutations observed were T143M and K122R, whereas in Egypt 14.8% presented with mutations in the MHR, and eight different mutations were discovered: R122K, S143L, L109P, S114P, S117N, P127S, P127T and Y134F. 2019 PeerJ Discussion HIV L109P;R122K;S114P;S117N;S143L;Y134F 191;177;198;205;184;229 196;182;203;210;189;234 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. The prevalence of HBsAg escape mutants in Jordan was 18.9%, with the R122K mutation which affects HBV detection being the most prevalent type. 2019 PeerJ Discussion HIV R122K 69 74 30867996 Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan. This is comparable to a study done in Iran, which showed that the frequency of 14% major hydrophilic region mutations (MHR), with the most frequent ones of P120T/S and R122K/T. 2019 PeerJ Discussion HIV R122K;R122T 168;168 175;175 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. As expected, K65R was only found from the group of TDF-exposed patients (group-B). 2019 BMC infectious diseases Discussion HIV K65R 13 17 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Even though the analysis of CRF02_AG versus non-AG showed no major effect of the local subtype distribution on emerging DRMs, molecular epidemiology surveillance merits further investigations, which include the preferential pattern of L74I as a potential signature in CRF02_AG-infected patients. 2019 BMC infectious diseases Discussion HIV L74I 235 239 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. Of note, K65R is a mutation known to reverse the excision phenotype of AZT resistance mutations, to increase viral susceptibility to AZT, which in turns improves the clinical efficacy of AZT. 2019 BMC infectious diseases Discussion HIV K65R 9 13 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. The very high frequency of M184 V (> 80%) underscores the utility of this mutation as an indicator of therapeutic compliance in clinical practice for patients receiving any regimen containing 3TC or FTC. 2019 BMC infectious diseases Discussion HIV M184V 27 33 30871487 HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. This is due to the selection of DRMs (TAMs and/or K65R) following previous ART with a thymidine analogue- and subsequently with TDF-containing regimens. 2019 BMC infectious diseases Discussion HIV K65R 50 54 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Along with the DRMs displayed at codon 138, the polymorphic accessory mutations G140K, G140R, G163R and L74I (5.5% for each) in the IN gene were also observed in our study. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G140K;G140R;G163R;L74I 80;87;94;104 85;92;99;108 IN 132 134 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Although L74I and G163R are usually selected by INSTI drugs, they have also been reported in INSTI-naive patients at rates similar to those reported in the present study; alone, they do not appear to be associated with reduced INSTI susceptibility. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G163R;L74I 18;9 23;13 INSTI;INSTI;INSTI 48;93;227 53;98;232 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Concerning the variation at codon 140, the mutations G140K and G140R appear to be unusual mutations associated with polymorphism. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G140K;G140R 53;63 58;68 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Consequently, the HIV-1 strains carrying these unusual polymorphic mutations (G140K/R) would develop less cross-resistance to different classes of INSTI drugs compared with HIV-1 strains that do not harbour these polymorphic mutations. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G140K;G140R 78;78 85;85 INSTI 147 152 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Contrary to our observations, E138T has been previously described as a rare non-polymorphic INSTI-selected mutation. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E138T 30 35 INSTI 92 97 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Furthermore, previous studies evaluating the variability of the IN gene revealed that amino acid variations at codon 138 (E138A/D/K/T) could arise from G-to-A hypermutation resulting from APOBEC-mediated RNA editing, and also from natural polymorphism during viral replication. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E138A;E138D;E138K;E138T 122;122;122;122 133;133;133;133 IN 64 66 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. However, polymorphism at position 140, similar to that observed in our study (G140K/R), has been described as leading to a higher genetic barrier for non-B subtypes to acquire the usual accessory INSTI-selected DRMs G140A/C/S at this position. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G140A;G140C;G140K;G140R;G140S 216;216;78;78;216 225;225;85;85;225 INSTI 196 201 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. In this study, one child exhibited the DRM E138K, conferring potential low-level resistance to dolutegravir and intermediate resistance to raltegravir and elvitegravir according to the Stanford University algorithm. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E138K 43 48 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Indeed, at position 140, the usual INSTI-selected accessory mutations are G140A/C/S, which are associated with a 3- to 5-fold reduction in susceptibility to elvitegravir when they occur alone. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G140A;G140C;G140S 74;74;74 83;83;83 INSTI 35 40 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Only two (11.1%) children harboured INSTI DRMs at codon 138 (E138K/T), known to usually display primary major INSTI-selected resistance mutations. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E138K;E138T 61;61 68;68 INSTI;INSTI 36;110 41;115 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Otherwise, in our study we found that a large proportion (9/13; 69.2%) of the HIV-1 strains remained susceptible to second-generation rilpivirine, which has also been described as a good candidate for an optimized dolutegravir-based treatment, although the presence of the K103N mutation could limit the efficiency of rilpivirine. 2019 The Journal of antimicrobial chemotherapy Discussion HIV K103N 273 278 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. The other mutation at codon 138 observed in our study was E138T, conferring potential low-level resistance to dolutegravir and low-level resistance to raltegravir and elvitegravir according to the Stanford University algorithm. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E138T 58 63 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Two (11.1%) children harboured INSTI DRMs at codon 138 (E138K/T), known to usually display primary major INSTI-selected resistance mutations according to the Stanford University algorithm. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E138K;E138T 56;56 63;63 INSTI;INSTI 31;105 36;110 30891603 High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO. Usually, E138K is a non-polymorphic mutation selected in the case of virological failure in patients receiving raltegravir, elvitegravir or dolutegravir. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E138K 9 14 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. At most, G112D RT showed a slight reduction in susceptibility to AZTTP. 2019 Journal of virology Discussion HIV G112D 9 14 RT 15 17 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Because M230I alters the organization of the polymerase active site through its interactions with the primer strand, it has two roles: (i) it interacts directly with a bound NNRTI and (ii) it interacts with, and affects, the positioning of the nucleic acid. 2019 Journal of virology Discussion HIV M230I 8 13 Pol;NNRTI 45;174 55;179 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Because the 3' end of the primer strand and corresponding portion of the template strand are an integral part of the polymerase active site, M230I could affect the positioning of the end of the primer strand at the polymerase active site. 2019 Journal of virology Discussion HIV M230I 141 146 Pol;Pol 117;215 127;225 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Because the M230I and G112D mutations alter the polymerase active site, we considered the possibility that one, or both, of these mutations could affect the incorporation of, or susceptibility to, NRTITPs, especially those that have structural features that lie outside the substrate envelope of a normal dNTP (e.g., AZTTP or FTCTP). 2019 Journal of virology Discussion HIV G112D;M230I 22;12 27;17 Pol;Env 48;284 58;292 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Conversely, G112D, which is quite near the polymerase active site, can affect NRTI susceptibility directly and NNRTI susceptibility indirectly. 2019 Journal of virology Discussion HIV G112D 12 17 Pol;NNRTI;NRTI 43;111;78 53;116;82 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D by itself has no measurable effects on the incorporation of normal dNTPs. 2019 Journal of virology Discussion HIV G112D 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. G112D causes a reduction in both FTCTP and 3TCTP incorporation into DNA. 2019 Journal of virology Discussion HIV G112D 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. However, combining G112D with M230I further reduced the susceptibility of RT to NNRTIs. 2019 Journal of virology Discussion HIV G112D;M230I 19;30 24;35 NNRTI;RT 80;74 86;76 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. However, its effects on both the susceptibility of RT to both NNRTIs and NRTIs in the presence of the M230I mutation point to the importance of the nucleic acid component in the structure and function of the polymerase active site, not only for normal polymerization but also for inhibition by anti-RT drugs, including NNRTIs. 2019 Journal of virology Discussion HIV M230I 102 107 Pol;NNRTI;NNRTI;NRTI;RT;RT 208;62;319;73;51;299 218;68;325;78;53;301 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. However, RT containing the M230I mutation has not been extensively studied biochemically, and whether this mutation affects the positioning of the primer strand is not known. 2019 Journal of virology Discussion HIV M230I 27 32 RT 9 11 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. If the G112D mutation alters the active site in a way that would permit the translocation of an AZTMP at the end of the primer from the N to the P site, excision by RT would be reduced, and this would explain why the mutants are hypersensitive to AZT. 2019 Journal of virology Discussion HIV G112D 7 12 RT 165 167 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. In contrast, M230I causes hypersensitivity to FTCTP and 3TCTP, which indicates that both of these analogs are better able to compete with dCTP for binding and incorporation by the M230I mutant RT. 2019 Journal of virology Discussion HIV M230I;M230I 13;180 18;185 RT 193 195 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. In HIV-2 RT, G112E is in a position that is equivalent to G112 in HIV-1 RT. 2019 Journal of virology Discussion HIV G112E 13 18 RT;RT 9;72 11;74 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. In HIV-2 RT, whose structure is closely related to the structure of HIV-1 RT, a phenylmethylthiazolylthiourea (PETT) derivative, MSK-076, selected for the mutations A101P and G112E. 2019 Journal of virology Discussion HIV A101P;G112E 165;175 170;180 RT;RT 9;74 11;76 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. In this study, we showed that the G112D, M230I, and G112D/M230I mutations significantly decrease the ability of RT to excise AZTMP using ATP. 2019 Journal of virology Discussion HIV G112D;G112D;M230I;M230I 34;52;41;58 39;57;46;63 RT 112 114 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Interestingly, the viral mutants selected with compound 13 had two unusual mutations, M230I and G112D, which seem to work together. 2019 Journal of virology Discussion HIV G112D;M230I 96;86 101;91 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. It is likely that this is also a result of the effects of M230I on the primer grip region of RT. 2019 Journal of virology Discussion HIV M230I 58 63 RT 93 95 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. It is not immediately apparent from its location, near the polymerase active site, how G112D is able to interact with M230I to reduce the susceptibility of RT to NNRTIs. 2019 Journal of virology Discussion HIV G112D;M230I 87;118 92;123 Pol;NNRTI;RT 59;162;156 69;168;158 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230 is in the periphery of the hydrophobic pocket that binds NNRTIs, and M230I is a known resistance mutation that has been selected by RPV in cell culture. 2019 Journal of virology Discussion HIV M230I 74 79 NNRTI 62 68 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I can affect NNRTI susceptibility by altering the NNRTI binding pocket directly. 2019 Journal of virology Discussion HIV M230I 0 5 NNRTI;NNRTI 17;54 22;59 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I can also affect the binding of nucleic acid by altering the primer grip region, which indirectly affects the structure of the polymerase active site and NRTI susceptibility. 2019 Journal of virology Discussion HIV M230I 0 5 Pol;NRTI 132;159 142;163 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. M230I has the smallest effect on excision, which agrees with the data obtained in the virology assays. 2019 Journal of virology Discussion HIV M230I 0 5 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Most NRTI resistance mutations interfere with the incorporation of the NRTITP, either directly (e.g., M184V/I, which causes steric hindrance involving the oxathiolane ring of 3TCTP or FTCTP) or indirectly (e.g., K65R altering the ability of the RT to bind tenofovir relative to dATP). 2019 Journal of virology Discussion HIV K65R;M184I;M184V 212;102;102 216;109;109 NRTI;RT 5;245 9;247 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. One study showed that M230I could compensate for the deleterious effects of the Y115W mutation in HIV-1 RT, suggesting that the M230I mutation affected the primer grip. 2019 Journal of virology Discussion HIV M230I;M230I;Y115W 22;128;80 27;133;85 RT 104 106 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Our results suggest that by itself, the M230I mutation has a deleterious effect on the ability of RT to extend a primer. 2019 Journal of virology Discussion HIV M230I 40 45 RT 98 100 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Some mutations in the RT active site, including M184I/V, cause AZT hypersensitivity by reducing the ability of RT to excise AZTMP. 2019 Journal of virology Discussion HIV M184I;M184V 48;48 55;55 RT;RT 22;111 24;113 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The effect of the G112D mutation on NNRTI susceptibility is relatively modest and might affect the bound nucleic acid. 2019 Journal of virology Discussion HIV G112D 18 23 NNRTI 36 41 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The most likely explanation is that the alterations in the trajectory of the nucleic acid substrate caused by M230I affect the polymerase active site in a way that allows FTCP and 3TCTP to be incorporated more efficiently. 2019 Journal of virology Discussion HIV M230I 110 115 Pol 127 137 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The NNRTIs VRX-329747 and VRX-413638 selected for multiple mutations in HIV-1 RT, including G112S. 2019 Journal of virology Discussion HIV G112S 92 97 NNRTI;RT 4;78 10;80 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The portions of the oxathiolane ring that lie outside the envelope defined by the bound deoxyribose allow mutant forms of RT, particularly M184V/I RT, to distinguish between the normal substrate dCTP and the analogs FTCTP and 3TCTP. 2019 Journal of virology Discussion HIV M184I;M184V 139;139 146;146 Env;RT;RT 58;122;147 66;124;149 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. The primary resistance mutations to AZT are T215F/Y and/or K70R. 2019 Journal of virology Discussion HIV K70R;T215F;T215Y 59;44;44 63;51;51 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. Therefore, it is probable that G112D and M230I interact through their effects on the bound nucleic acid. 2019 Journal of virology Discussion HIV G112D;M230I 31;41 36;46 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. These resistance mutations were mapped on the structure of HIV-2 RT, and A101P is near the NNRTI-binding site of HIV-1 RT. 2019 Journal of virology Discussion HIV A101P 73 78 NNRTI;RT;RT 91;65;119 96;67;121 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. This strengthens the argument that the effects of the two mutations, G112D and M230I, intersect at the active site and involve the positioning of the nucleic acid substrate. 2019 Journal of virology Discussion HIV G112D;M230I 69;79 74;84 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. This suggests that the G112D could also reduce AZTMP excision. 2019 Journal of virology Discussion HIV G112D 23 28 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. We asked whether the G112D and M230I mutations affected the incorporation of FTCTP. 2019 Journal of virology Discussion HIV G112D;M230I 21;31 26;36 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. We propose that the G112D mutation opposes the displacement of the end of the viral DNA from the active site. 2019 Journal of virology Discussion HIV G112D 20 25 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. When RPV is bound to HIV-1 RT, M230I is near the cyanovinyl group on the longer side chain of RPV. 2019 Journal of virology Discussion HIV M230I 31 36 RT 27 29 30894467 Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs. While G112D alone had little effect on susceptibility to NNRTIs, M230I reduced susceptibility to all of the NNRTIs tested. 2019 Journal of virology Discussion HIV G112D;M230I 6;65 11;70 NNRTI;NNRTI 57;108 63;114 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. As an additional test, we used a new fluorescence imaging assay that can quantify the number of CypA molecules interacting with native viral capsids to compare one of the mutants (A25D) to the wild type protein, but we observed no differences in affinity. 2019 Retrovirology Discussion HIV A25D 180 184 Capsid 141 148 30947724 Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A. Our in-vitro measurements of CypA-CA interactions utilized primarily self-assembled CA A14C/E45C tubes, which are similar in structure to the wild type CA tubes used previously to determine the cryoEM structure of the complex. 2019 Retrovirology Discussion HIV A14C;E45C 87;92 91;96 Capsid;Capsid;Capsid 34;84;152 36;86;154 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. However, it should be noted that for about half (49.1%) of HIV-1 strains with drug resistant mutations, the degree of resistance was classified as potential low-level due to the single V179D/E mutation, which is selected by NNRTI and contribute low-levels reductions in susceptibility to each of the NNRTIs. 2019 BMC infectious diseases Discussion HIV V179D;V179E 185;185 192;192 NNRTI;NNRTI 224;300 229;306 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. Moreover, about half (49.1%, 27/55) of the virus strains with mutations presented as potential low-level resistant to NNRTI ascribed to V179D/E. 2019 BMC infectious diseases Discussion HIV V179D;V179E 136;136 143;143 NNRTI 118 123 30961560 Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. The trend of increasing V179D/E mutation in genotype CRF01_AE among MSM population was also reported in other study. 2019 BMC infectious diseases Discussion HIV V179D;V179E 24;24 31;31 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. Of note, in our survey, R263K signature mutation that affects the efficacy of DTG was not observed. 2019 Revista espanola de quimioterapia Discussion HIV R263K 24 29 31037930 Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey. The three main mutational pathways were described, with a clear predominance of N155H. 2019 Revista espanola de quimioterapia Discussion HIV N155H 80 85 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Although the in vitro replication capacity mutants containing E92Q or G118R was markedly reduced, their transmission fitness is not known as it is also unknown if their transmission potential may be increased if viremias are high as it is the case of acute HIV infection. 2019 Nature communications Discussion HIV E92Q;G118R 62;70 66;75 HIV infections 251 270 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. G118R is a rare non-polymorphic mutation that can cause 5-20-fold resistance to INSTIs in HIV and also resistance to DTG, RAL and EVG in SIV. 2019 Nature communications Discussion HIV G118R 0 5 INSTI 80 86 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. However, the maintenance of G118R and E92G in two of the macaques when CAB levels were low or undetectable suggests a risk of resistance selection during the CAB drug tail. 2019 Nature communications Discussion HIV E92G;G118R 38;28 42;33 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. In humans, treatment with CAB or CAB LA has been associated with rare instances of selection of Q148R. 2019 Nature communications Discussion HIV Q148R 96 101 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. It will be important to see if the G118R, G140R and E92Q/G mutations selected in SIV in vivo will also be selected in patients failing CAB-containing regimens, and if these mutations will confer similar levels of drug resistance in HIV. 2019 Nature communications Discussion HIV E92G;E92Q;G118R;G140R 52;52;35;42 58;58;40;47 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Likewise, E92G, a rare non-polymorphic mutation that in HIV confers resistance to EVG, was associated with reduced susceptibility to CAB (3.5-fold) and EVG (3.7-fold). 2019 Nature communications Discussion HIV E92G 10 14 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Overall, these results demonstrate intermediate to high-level resistance to CAB and other INSTIs due to G118R, G140R and E92Q/G. 2019 Nature communications Discussion HIV E92G;E92Q;G118R;G140R 121;121;104;111 127;127;109;116 INSTI 90 96 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The E92Q mutation previously characterized as a mutation conferring resistance to EVG in SIV and HIV was also associated with 2.5-fold resistance to CAB. 2019 Nature communications Discussion HIV E92Q 4 8 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. The impact of G140R in HIV is not known although other non-polymorphic mutations at position 140 including G140S/A/C are associated with 10-100-fold reduced susceptibility of HIV to RAL, EVG, and DTG. 2019 Nature communications Discussion HIV G140A;G140C;G140R;G140S 107;107;14;107 116;116;19;116 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. These findings were consistent with CAB concentrations in rectal fluids that were above 4xPA-IC90, and raise important concerns about potential secondary transmission of these mutants, particularly since E92Q and G118R were able to persist in rectal fluids for 1-2 months. 2019 Nature communications Discussion HIV E92Q;G118R 204;213 208;218 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. This scenario differs from that of other PrEP drugs such as FTC, which can rapidly select for the M184V/I mutation within days or weeks. 2019 Nature communications Discussion HIV M184I;M184V 98;98 105;105 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. Unfortunately, SHIV RNA was difficult to amplify from vaginal fluids, although we found E92Q in the only female animal that had detectable drug-resistant viruses in plasma. 2019 Nature communications Discussion HIV E92Q 88 92 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. We also found that G118R, E92Q, E92G, and G140R were associated with marked reductions in viral replicative capacity, a finding that is line with that seen in HIV-1. 2019 Nature communications Discussion HIV E92G;E92Q;G118R;G140R 32;26;19;42 36;30;24;47 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. We document selection of G118R, G140R, and E92Q/G, all of which have been associated with resistance to INSTIs in HIV-1 and in some instances SIV. 2019 Nature communications Discussion HIV E92G;E92Q;G118R;G140R 43;43;25;32 49;49;30;37 INSTI 104 110 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. We found that G118R conferred 345-1000-fold resistance to all five INSTIs. 2019 Nature communications Discussion HIV G118R 14 19 INSTI 67 73 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. We show here that, in SIV, G140R confers 345 to >1000-fold resistance to all five INSTIs, thus expanding the resistance profile associated with changes at position 140. 2019 Nature communications Discussion HIV G140R 27 32 INSTI 82 88 31043606 Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection. While virus shedding was reduced among CAB-treated animals, the finding of E92Q and G118R in viruses from rectal fluids was noteworthy as it suggested that CAB concentrations in the rectal mucosa were sufficient to select and/or maintain drug-resistant viruses. 2019 Nature communications Discussion HIV E92Q;G118R 75;84 79;89 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. In contrast, PR mutant with the single substitution of R8Q, which completely eliminated the ion pair with Asp29', showed decreased stability with UC50 of 0.7 relative to wild type enzyme. 2019 Biochemical and biophysical research communications Discussion HIV R8Q 55 58 Asp;PR 106;13 109;15 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. Overall, the loss of internal contacts among flap residues and disruption of the ion pair between Arg8 and Asp29' are consistent with molecular dynamics simulations suggesting substitutions V32I, I47V and V82I in HIV-2 PR decrease the hydrophobic interactions with APV and DRV. 2019 Biochemical and biophysical research communications Discussion HIV I47V;V32I;V82I 196;190;205 200;194;209 Asp;PR 107;219 110;221 31092330 Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I. This new structure of PRTri/1 suggests how drug resistant mutations of V32I and I47V on opposite sides of the S2 and S2' subsites can partially compensate for altered hydrophobic interactions with inhibitors and other protease residues, while mutation V82I induces alternate conformations of Arg8/8' and introduces new interactions with Leu10 and the P2 group of 1. 2019 Biochemical and biophysical research communications Discussion HIV I47V;V32I;V82I 80;71;252 84;75;256 PR 218 226 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Also, in combination with accessory mutations at positions 62, 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC and intermediate-level resistance to TDF, 3TC, and FTC. 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV Q151M 80 85 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. M184V was the most commonly observed NRTI-associated mutation in both groups (64% in HIV-TB patients and 76% in HIV-positive patients). 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV M184V 0 5 NRTI 37 41 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. Q151M mutations cause intermediate-/high-level resistance to AZT, ddI, d4T, and ABC with low-level resistance to TDF, 3TC, and FTC. 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV Q151M 0 5 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. The high prevalence of thymidine analog mutations in the patients included in this study might explain the increased DRMs in HIV and HIV-TB patients despite the known protective role of the M184V mutation. 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV M184V 190 195 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. The Q151M mutation was observed in 2 patients with HIV alone. 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV Q151M 4 9 31117863 HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting. This patient had 3 thymidine analog mutations, and the M184V mutation, which makes it resistant to all NRTIs. 2019 Journal of the International Association of Providers of AIDS Care Discussion HIV M184V 55 60 NRTI 103 108 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Also, solution studies of PRS17-D25N by NMR demonstrated that the inhibitor-free PRS17-D25N adopts a flap conformation very similar to that of the inhibitor-free active PRS17 crystal structure. 2019 ACS omega Discussion HIV D25N;D25N 32;87 36;91 PR;PR;PR 26;81;169 28;83;171 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Among the 17 mutations in PRS17, G48V and V82S play critical roles in the binding of CA-p2 and p2-NC substrate analogues. 2019 ACS omega Discussion HIV G48V;V82S 33;42 37;46 NC;Capsid;PR 98;85;26 100;87;28 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Crystal structures of inactivated PR with active-site D25N and V82A mutations in complex with substrates CA-p2, p1-p6, and MA-CA show high structural similarity with inactivated PR-D25N/substrate complexes, which indicates that V82A mutation in conjunction with active-site D25N does not affect substrate binding. 2019 ACS omega Discussion HIV D25N;D25N;D25N;V82A;V82A 54;181;274;63;228 58;185;278;67;232 Gag;Matrix;Capsid;Capsid;PR;PR 115;123;105;126;34;178 117;125;107;128;36;180 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. F53L single mutant, which exhibits curled flaps, was shown to possess a 15% lower catalytic efficiency and a 20-fold weaker inhibition by clinical drug indinavir. 2019 ACS omega Discussion HIV F53L 0 4 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. G48V is associated with V82A in saquinavir resistance and this pair occurs as a mutational cluster together with nonactive-site mutant C95F, which emphasizes the importance of coevolution of mutations at 48 and 82 in drug resistance. 2019 ACS omega Discussion HIV C95F;V82A;G48V 135;24;0 139;28;4 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. G48V mutation is also selected by PR inhibitors atazanavir, indinavir, lopinavir, and nelfinavir.- G48M has a similar resistance profile as G48V. 2019 ACS omega Discussion HIV G48M;G48V;G48V 99;140;0 103;144;4 PR 34 36 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. However, in the presence of G48V flap mutation, mutations of residue 82 to larger side chains like V82F, V82L, and V82I may interfere with the binding of substrates, while smaller V82S and V82A mutations might play a vital role in both enhanced binding of substrate and increased resistance to PIs through the structural shift of 80's loop. 2019 ACS omega Discussion HIV G48V;V82A;V82F;V82I;V82L;V82S 28;189;99;115;105;180 32;193;103;119;109;184 PI 294 297 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. However, mutations in the Gag substrate cleavage sites can coevolve with resistance-associated mutations in HIV PR or mutations that alter the fitness of HIV PR.- NC-p1 cleavage site, which is the rate-limiting step in Gag polyprotein processing, has been reported to coevolve with Ala to Val mutation at the P2 position of the substrate in response to V82A-resistant mutation. 2019 ACS omega Discussion HIV V82A 353 357 Gag;Gag;NC;PR;PR 26;219;163;112;158 29;222;165;114;160 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In addition to G48V, other flap mutations M46L and I54V may also contribute to curling in PRS17. 2019 ACS omega Discussion HIV G48V;I54V;M46L 15;51;42 19;55;46 PR 90 92 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In particular, flap mutation G48V confers a high level of resistance to saquinavir. 2019 ACS omega Discussion HIV G48V 29 33 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. In the absence of G48V mutation, Val82 mutations enhance the resistance profile of PR through steric hindrance to inhibitors at the binding site. 2019 ACS omega Discussion HIV G48V 18 22 PR 83 85 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Kinetic studies have shown that PR bearing the single V82A mutation has a significantly worse affinity for PR inhibitors indinavir, nelfinavir, ritonavir, and DRV, while smaller effects were seen for the cleavage of PR substrate.- Structural studies on V82A mutant in complexes with nelfinavir, indinavir, ritonavir, DRV, and saquinavir all reveal a small shift in residues to accommodate the inhibitor, explaining the cross-resistance profile of this mutation to all PR inhibitors. 2019 ACS omega Discussion HIV V82A;V82A 54;253 58;257 PR;PR;PR;PR 32;107;216;468 34;109;218;470 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Less prevalent resistance mutations G48A/S/T/Q are less well studied and their clinical significance is not fully understood. 2019 ACS omega Discussion HIV G48A;G48Q;G48S;G48T 36;36;36;36 46;46;46;46 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Resistance mutations like V82A at the active site of HIV PR interfere with the binding of drugs; however, replication of the virus requires successful binding and hydrolysis of Gag and Gag-Pol substrates by resistant PR variants. 2019 ACS omega Discussion HIV V82A 26 30 GagPol;Gag;PR;PR 185;177;57;217 192;180;59;219 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The crystal structure of unliganded PRS17-D25N exhibits curling of flap tips in comparison to unliganded wild-type structure. 2019 ACS omega Discussion HIV D25N 42 46 PR 36 38 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The current crystal structure of PRS17-D25N further confirms that the conformation changes observed in the flaps of the two unliganded structures of PRS17 are due to the mutations. 2019 ACS omega Discussion HIV D25N 39 43 PR;PR 33;149 35;151 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The current structural studies of PRS17 strongly suggest that G48V mutation plays an important role in the enhanced binding of substrate analogues CA-p2 and p2-NC. 2019 ACS omega Discussion HIV G48V 62 66 NC;Capsid;PR 160;147;34 162;149;36 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The flap twisting initiated by G48V mutation in PRS17 is implicated in the cross-resistance of PRS17 to multiple clinical drugs including DRV even though it lacks any major mutations associated with DRV resistance. 2019 ACS omega Discussion HIV G48V 31 35 PR;PR 48;95 50;97 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The G48V mutation in PRS17 also confers resistance to PR inhibitors and blocks the flap-binding site for P3 Arg of CA-p2 observed in the various wild-type PR complexes. 2019 ACS omega Discussion HIV G48V 4 8 Capsid;PR;PR;PR 115;21;54;155 117;23;56;157 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. The side chains of mutations vary in size from the smaller V82A to bulkier V82F in addition to V82S, V82T, V82L, and V82I that are in between. 2019 ACS omega Discussion HIV V82A;V82F;V82I;V82L;V82S;V82T 59;75;117;107;95;101 63;79;121;111;99;105 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. This flap curling is initiated by G48V mutation with a ~172 change in phi angle in comparison to PR wild type and extends up to Gly52'. 2019 ACS omega Discussion HIV G48V 34 38 PR 98 100 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. Twisting of flaps observed in the recently reported PR with 22 mutations in addition to inactivating D25N mutation has >175-fold resistance to DRV in addition to APV. 2019 ACS omega Discussion HIV D25N 101 105 PR 52 54 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. V82A is one of the earlier PR mutations to occur at the active site among patients undergoing antiviral therapy and has been the best-studied mutation at position 82. 2019 ACS omega Discussion HIV V82A 0 4 PR 27 29 31172041 Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues. With P3 Arg bound at the preferred wild-type flap-binding site, mutations at 82 with large side chains like V82F, V82I, or V82L hinder the binding of PR inhibitors, thereby altering PR susceptibility to PIs while retaining binding to substrates. 2019 ACS omega Discussion HIV V82F;V82I;V82L 108;114;123 112;118;127 PI;PR;PR 203;150;182 206;152;184 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. In a previous pre-treatment HIV-DR study, NNRTI resistance was K103N, Y181C, Y188C and G190A, and NRTI resistance was V75M and M184V. 2019 Infection and drug resistance Discussion HIV G190A;K103N;M184V;V75M;Y181C;Y188C 87;63;127;118;70;77 92;68;132;122;75;82 NNRTI;NRTI 42;98 47;102 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Patients receiving incomplete suppressive 3TC regimens usually develop M184V as their first mutation. 2019 Infection and drug resistance Discussion HIV M184V 71 76 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. Regarding, 88.4% of patients had HIV-DR in first-line ART failures was the M184V mutation. 2019 Infection and drug resistance Discussion HIV M184V 75 80 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. TAMs occur in different patterns: type 1 includes M41L, L210W and T215Y (14%, 11.6% and 4.7% prevalence, respectively, in our study), and type 2 includes K70R, D67N T215F and K219Q/E (37.2%, 27.9%, 27.9% and 14% prevalence, respectively, in our study). 2019 Infection and drug resistance Discussion HIV D67N;K219E;K219Q;K70R;L210W;M41L;T215F;T215Y 160;175;175;154;56;50;165;66 164;182;182;158;61;54;170;71 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. The accumulation of other mutations observed included TAMs (including M41L, L210W, T215Y, K70R, D67N, T215F and K219Q), resulting in increased resistance to AZT, TDF, D4T, ABC and ddI. 2019 Infection and drug resistance Discussion HIV D67N;K219Q;K70R;L210W;M41L;T215F;T215Y 96;112;90;76;70;102;83 100;117;94;81;74;107;88 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. The T215Y mutation was observed in 4.7% of the sequences, whereas T215F was detected in 27.9%. 2019 Infection and drug resistance Discussion HIV T215F;T215Y 66;4 71;9 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. This finding can be explained by the M184V mutation in line with lamivudine (3TC) resistance. 2019 Infection and drug resistance Discussion HIV M184V 37 42 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. This result was in line with that of Yahi N et al, who found that T215F mutation was preferentially associated with K70R (>71%), D67N (>73%) and K219Q/E/N (>76%), whereas T215Y mutation was associated with M41L (>84%) and L210W (>58%). 2019 Infection and drug resistance Discussion HIV D67N;K219E;K219N;K219Q;K70R;L210W;M41L;T215F;T215Y 129;145;145;145;116;222;206;66;171 133;154;154;154;120;227;210;71;176 31190911 Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam. This result was more highly observed than other mutations similar to the findings of other studies: Winand et al (M184V: 44.0%, n=3,554) and El Annaz et al (M184V: 44.0%, n=45). 2019 Infection and drug resistance Discussion HIV M184V;M184V 114;157 119;162 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. About 21 mutations performed in tetherin at positions L22, L23, L24, G25, I26, L29, V30, I33, I34, I36, L37, V39, P40, L41, F44, and T45, wherein single point mutations of L23 Y, L24 T, and P40 T depicted a decrease in residue pairs involved in hydrophobic interactions in the Vpu-mutant tetherin complex. 2019 Medical sciences (Basel, Switzerland) Discussion HIV L23Y;L24T;P40T 172;179;190 177;184;195 Vpu 277 280 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. On similar lines, these alanine residues are mutated in our study and, as mutation in A15F is observed to have higher downregulation activity than A19F in a study by Li et al., A15T and A19H mutation in our study resulted in reduced hydrophobic interactions, suggesting the absence of a strong connection must be impacting the tilt of the Alanine rim. 2019 Medical sciences (Basel, Switzerland) Discussion HIV A15F;A15T;A19F;A19H 86;177;147;186 90;181;151;190 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. Out of the 22 mutations performed in blood-derived Vpu at S3, Q5, L7, A8, V10, A11, V14, A15, I17, I18, A19, W23, I25, F27, R31, and K32 single point mutations of A19 H and W23 Y affected the hydrophobic interactions in mutant Vpu and tetherin, while combined mutations of {V10K, A11L, A19T}, {V14T, I18T, I26S}, and {A11T, V14L, A15T} showed minimal hydrophobic connections and low binding affinities in the docked complexes, as represented in Figure 7. 2019 Medical sciences (Basel, Switzerland) Discussion HIV A11L;A11T;A15T;A19H;A19T;I18T;I26S;V10K;V14L;V14T;W23Y 280;318;330;163;286;300;306;274;324;294;173 284;322;334;168;290;304;310;278;328;298;178 Vpu;Vpu 51;227 54;230 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. The binding affinities (DeltaG) of the L23Y, L24T, and P40T mutants were -2.6, -2.2, and -2.7 kcal/mol with corresponding dissociation constants (Kd) of 1.2 x 10-3, 2.9 x 10-3, and 1.9 x 10-3 M, respectively. 2019 Medical sciences (Basel, Switzerland) Discussion HIV L23Y;L24T;P40T 39;45;55 43;49;59 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. The combined/multiple mutations at {L22S, F44Y, L37I} and {L23T, L37T, T45I} showed minimal hydrophobic connections and low binding affinities in Vpu-tetherin complexes with binding affinities (DeltaG) and dissociation constant (Kd) of -2.2 kcal/mol and 1.8 x 10-2 M and -2.9 kcal/mol and 2.3 x 10-2 M, respectively. 2019 Medical sciences (Basel, Switzerland) Discussion HIV F44Y;L22S;L23T;L37I;L37T;T45I 42;36;59;48;65;71 46;40;63;52;69;75 Vpu 146 149 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. The docked complexes of A19H and W23Y Vpu mutants possessed binding affinities (DeltaG) as -2.5 and -2.1 kcal/mol and Kd of 2.9 x 10-3 and 2.1 x 10-3 M, while the complexes with triple mutations {V10K, A11L, A19T}, {V14T, I18T, I26S}, and {A11T, V14L, A15T} had binding affinities (DeltaG) of -2.6, -2.7, and -2.3 kcal/mol and the corresponding Kds of 2.1 x 10-5, 2.2 x 10-4, and 2.8 x 10-2 M, respectively. 2019 Medical sciences (Basel, Switzerland) Discussion HIV A11L;A11T;A15T;A19H;A19T;I18T;I26S;V10K;V14L;V14T;W23Y 202;240;252;24;208;222;228;196;246;216;33 206;244;256;28;212;226;232;200;250;220;37 Vpu 38 41 31234536 In Silico Insights into HIV-1 Vpu-Tetherin Interactions and Its Mutational Counterparts. The reported T45I single mutation that causes tetherin to become resistant to Vpu-mediated depletion was also tested in our study. 2019 Medical sciences (Basel, Switzerland) Discussion HIV T45I 13 17 Vpu 78 81 31257432 Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda. All individuals with ADR had NNRTI mutations with K103N/S, Y181C, K101E/Q and G190S/A being more prevalent, depicting extensive use of the NNRTIs nevirapine and efavirenz in first-line regimens in this setting. 2019 The Journal of antimicrobial chemotherapy Discussion HIV G190A;G190S;K101E;K101Q;K103N;K103S;Y181C 78;78;66;66;50;50;59 85;85;73;73;57;57;64 NNRTI;NNRTI 29;139 34;145 31257432 Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda. The K65R mutation, which is selected by lamivudine and tenofovir, was highly prevalent among VF cases in our study, which indicates the prolonged use of lamivudine and tenofovir in this setting. 2019 The Journal of antimicrobial chemotherapy Discussion HIV K65R 4 8 31257432 Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda. The most prevalent NRTI mutations, M184V/I, are selected by and cause high-level resistance to cytosine analogue NRTIs, lamivudine and emtricitabine. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 35;35 42;42 NRTI;NRTI 19;113 23;118 31257432 Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda. The rampant prevalence of the M184V/I and K65R mutations may not warrant the discontinuation of NRTI usage because these mutations confer increased susceptibility to zidovudine (a second-line regimen component in Uganda) and reduced virological fitness to HIV. 2019 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184I;M184V 42;30;30 46;37;37 NRTI 96 100 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. As shown in our study, the introduction of TDF without virological monitoring may result in an extensive evolution of the K65R mutation, especially since it is preferentially selected by HIV-1C in ex vivo and in vitro analysis. 2019 BMC infectious diseases Discussion HIV K65R 122 126 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. Importantly, strains with the K65R may be transmitted further which may jeopardize future therapeutic and prophylactic use of TDF and of tenofovir alafenamide. 2019 BMC infectious diseases Discussion HIV K65R 30 34 31262272 A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort. The treatment outcome of the different NRTI-based regimens did not differ, neither the extent of viral resistance at failure, although the K65R mutation was only found in TDF-treated patients. 2019 BMC infectious diseases Discussion HIV K65R 139 143 NRTI 39 43 31266818 Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study. Furthermore, consistent with findings from Rwanda, the most predominant mutations observed in this study were M184V for NRTI and K103N for NNRTIs. 2019 Sexually transmitted infections Discussion HIV K103N;M184V 129;110 134;115 NNRTI;NRTI 139;120 145;124 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Both mutants (I36T T and E35D G S) are in the hinge region but they show different properties. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV E35D;I36T 25;14 29;19 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. Interestingly the mutant studied here, also experience a E35D mutation, suggesting that it also does not have a E35-R57 salt bridge. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV E35D 57 61 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. M36I (present in the wild type) is reported to regulate the size of the binding cavity of the protease and influence the shape of the active site. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV M36I 0 4 PR 94 102 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The behaviour of the mutant could be caused by the E35D mutation. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV E35D 51 55 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The E35D mutation was reported to induce reduced binding affinities to PIs. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV E35D 4 8 PI 71 74 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The I36T T mutant showed an increased affinity for substrate and increased catalytic activity. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV I36T 4 8 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The mutant in this study though having different properties when compared to the previously reported mutant (I36T T), they both showed weaker binding to PIs. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV I36T 109 114 PI 153 156 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The variant we are studying contain an I36G mutation and showed weaker binding to NFV and had the worst IC50 result (Table 2 and Figure 4) with respect to this drug. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV I36G 39 43 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. The wild type contains only the M36I polymorphism. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV M36I 32 36 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. This observation is in contrast with what was observed in the I36T T mutant we recently reported. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV I36T 62 66 31409143 Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease. We proposed that I36G together with the other mutations in E35D G S caused the reduced binding energies of the PIs. 2019 Journal of enzyme inhibition and medicinal chemistry Discussion HIV E35D;I36G 59;17 63;21 PI 111 114 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. A recent study of suppressed participants with documented M184V/I by historical genotype showed that M184V/I was detected by the GenoSure Archive assay in only 43% (16/37) of cases. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184I;M184V;M184V 58;101;58;101 65;108;65;108 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Additionally, any potential benefit of decreased viral fitness by M184V/I on the efficacy of dolutegravir/lamivudine may not outweigh the risk of virological failure with INSTI-R development, as it is possible for M184V and INSTI-R to co-develop while failing a dolutegravir/lamivudine regimen.In vitro studies further suggest that viral fitness defects can be overcome by drug resistance in the presence of antiretroviral drugs: HIV-1 with M184V and INSTI-R (E92Q, Q148R or N155H) grows more efficiently than WT HIV-1 in the presence of emtricitabine and the INSTI elvitegravir at physiological concentrations. 2019 The Journal of antimicrobial chemotherapy Discussion HIV E92Q;M184I;M184V;M184V;M184V;N155H;Q148R 460;66;66;214;441;475;466 464;73;73;219;446;480;471 INSTI;INSTI;INSTI;INSTI 171;224;451;560 176;229;456;565 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Consequently, in medical practice emtricitabine/tenofovir-based treatment is continued in the context of M184V/I to maintain selective pressure for a less fit, tenofovir-hypersusceptible virus. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 105;105 112;112 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Extensive guanosine-to-adenosine (G-to-A) hypermutation by the cellular factor APOBEC3G can cause the M184I (but not M184V) substitution; however, APOBEC also induces stop codons rendering many of these genomes non-viable. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 102;117 107;122 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Given these limitations, the high frequencies of M184V/I and other resistance substitutions detected by proviral genotyping in studies 1878 and 1844 are likely an under-representation of total archived resistance. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 49;49 56;56 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. High rates of virological suppression for up to 48 weeks and the absence of treatment-emergent resistance indicate that the three-drug regimen BIC/FTC/TAF is a treatment option for suppressed patients, including those with evidence of archived resistance, such as M184V/I, or without historical resistance data. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 264;264 271;271 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. However, additional studies of BIC/FTC/TAF efficacy in viraemic patients are needed to further determine the utility of BIC/FTC/TAF in HIV-infected individuals harbouring M184V/I, which may increase the risk of further development of drug resistance. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 171;171 178;178 HIV infections 135 147 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. In studies 1878 and 1844, high levels of pre-existing resistance substitutions were detected among suppressed patients switching to BIC/FTC/TAF, including previously unidentified M184V/I in 54 participants. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 179;179 186;186 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. In studies 1878 and 1844, retrospective archive genotyping revealed previously undocumented M184V/I in a large subset of participants who were suppressed on boosted PI-based triple therapy (atazanavir or darunavir plus two NRTIs) or DTG/ABC/3TC and switched to BIC/FTC/TAF (10%). 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 92;92 99;99 NRTI;PI 223;165 228;167 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. In study 1878, one participant had reactivation of archived M184V during virological failure due to drug non-adherence, which substantiates the relevance of archived resistance. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184V 60 65 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. In vitro, viral isolates with M184V/I substitutions have reduced viral fitness and increased susceptibility to tenofovir. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 30;30 37;37 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. M184V/I substitutions are among the most common NRTI-R substitutions detected in HIV-infected individuals who have experienced virological failure on emtricitabine- or lamivudine-based therapy. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 0;0 7;7 NRTI 48 52 HIV infections 81 93 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Moreover, tenofovir hypersusceptibility of M184V/I may also play a role in the efficacy of tenofovir-containing three-drug regimens such as BIC/FTC/TAF against archived M184V/I, but this would not be applicable to dolutegravir/lamivudine. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184I;M184V;M184V 43;169;43;169 50;176;50;176 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Nonetheless, 10% (54/543) of participants had major pre-existing resistance to emtricitabine and lamivudine in the form of M184V or M184I. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 132;123 137;128 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. recently reported that a 15% proviral DNA deep sequencing cut-off only detected M184V in <50% of patients who had previously documented M184V, but with a 1% assay cut-off M184V was detected in almost 70%. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184V;M184V;M184V 80;136;171 85;141;176 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Resuppressed patients harbouring M184V/I may eventually need to switch regimens, but most guideline-recommended fixed-dose combinations containing emtricitabine or lamivudine are not indicated for patients with known resistance to any component of the regimen. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 33;33 40;40 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Switching suppressed patients with underlying M184V/I or rilpivirine resistance to a dual combination of dolutegravir/lamivudine or dolutegravir/rilpivirine, respectively, would result in functional dolutegravir monotherapy. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 46;46 53;53 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Taken together, current clinical and in vitro data suggest that BIC/FTC/TAF may be an effective treatment option for suppressed patients with archived M184V/I. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 151;151 158;158 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. The average time on ART therapy for participants with M184V/I was longer than that for those with WT M184; however, archived M184V/I was also detected in participants who initiated ART therapy <3 years ago. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184I;M184V;M184V 125;54;54;125 132;61;61;132 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. The baseline data from studies 1878 and 1844 suggest that pre-existing resistance to emtricitabine and lamivudine and NNRTIs such as rilpivirine is frequent in suppressed patient populations, with pre-existing M184V/I and rilpivirine resistance each detected in 10% of our participants. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 210;210 217;217 NNRTI 118 124 31430369 Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. Thus, all cases of pre-existing M184V/I should be considered clinically relevant when making treatment decisions. 2019 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 32;32 39;39 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Although there was no significant change in the prevalence of K103 N mutations before and after 2012 (P = 0.32), the K103 N TDR should be monitored closely because NNRTIs are still used as a first-line ART in Taiwan. 2019 BMC infectious diseases Discussion HIV K103N;K103N 62;117 68;123 NNRTI 164 170 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. As NNRTIs are still widely prescribed as a once-daily single tablet regimen, and combination ART consisting of 2 NRTIs and 1 NNRTI remains the recommended first-line regimen in the World Health Organization treatment guidelines for adults, close monitoring of the prevalence of K103 N mutations is important for further evaluation of first-line ART options and their effects on TDR. 2019 BMC infectious diseases Discussion HIV K103N 278 284 NNRTI;NNRTI;NRTI 3;125;113 9;130;118 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Both V179D and K103R are polymorphisms that by themselves do not predict treatment failure of EFV-based regimen. 2019 BMC infectious diseases Discussion HIV K103R;V179D 15;5 20;10 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Five individuals were found to have the combination V179D and K103R, and four-fifths of them were detected after 2012. 2019 BMC infectious diseases Discussion HIV K103R;V179D 62;52 67;57 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. However, the combination of V179D and K103R can have a synergistic effect to reduce susceptibility to NVP and EFV. 2019 BMC infectious diseases Discussion HIV K103R;V179D 38;28 43;33 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. In addition, virology studies have shown that K103 N, a major NNRTI mutation, can persist for a long time in the absence of treatment. 2019 BMC infectious diseases Discussion HIV K103N 46 52 NNRTI 62 67 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. In the present study, the most common drug resistance mutation observed in the patients was K103 N, which was found in 6 individuals. 2019 BMC infectious diseases Discussion HIV K103N 92 98 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. In the present study, the prevalence rates of V179D and K103R were 5.3 and 37.1%, respectively. 2019 BMC infectious diseases Discussion HIV K103R;V179D 56;46 61;51 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. K103 N causes high-level resistance to NVP and EFV. 2019 BMC infectious diseases Discussion HIV K103N 0 6 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Major INSTI mutations have been previously detected in treatment-naive HIV-infected patients from Taiwan, however only one strain has been found to harbor Q148R. 2019 BMC infectious diseases Discussion HIV Q148R 155 160 INSTI 6 11 HIV infections 71 83 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. reported that K103R substitutions most likely represent naturally occurring polymorphisms in HIV reverse transcriptase, and that they are not directly associated with NNRTI exposure or resistance. 2019 BMC infectious diseases Discussion HIV K103R 14 19 RT;NNRTI 97;167 118;172 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. Several previous studies have reported an association between the widespread use of NNRTIs and an increase in K103 N TDR. 2019 BMC infectious diseases Discussion HIV K103N 110 116 NNRTI 84 90 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. The slight increase in the prevalence of K103 N TDR may be a consequence of the introduction of a fixed regimen with NNRTIs as the first-line therapy in Taiwan during the study period. 2019 BMC infectious diseases Discussion HIV K103N 41 47 NNRTI 117 123 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. There was a high prevalence rate of K103R in our patients, however Harrigan et al. 2019 BMC infectious diseases Discussion HIV K103R 36 41 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. There was no significant increase in the prevalence of V179D or K103R between the two study periods (results not shown). 2019 BMC infectious diseases Discussion HIV K103R;V179D 64;55 69;60 31443633 Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan. This is because K103 N only has a limited effect on replicative capacity. 2019 BMC infectious diseases Discussion HIV K103N 16 22 31479466 National survey of pre-treatment HIV drug resistance in Cuban patients. The sustained use of NVP or EFV in the first therapeutic line could favor the accumulation of mutations associated with resistance to these drugs (K103N, G190A and Y181C) and the subsequent transmission of the variants with these changes to the population. 2019 PloS one Discussion HIV G190A;K103N;Y181C 154;147;164 159;152;169 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. 10A and B), Nef A15T might compensate for the impaired infectivity of the RGDA/Q112D+G94D virus. 2019 Journal of virology Discussion HIV A15T;G94D;Q112D 16;85;79 20;89;84 Nef 12 15 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. A limitation of this study is that we used an established series of CA mutations (RGDA/Q112D virus) as a starting viral backbone, since we previously aimed at making an HIV-1 clone with a high level of resistance to macaque TRIMCyp. 2019 Journal of virology Discussion HIV Q112D 87 92 Capsid 68 70 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. A similar phenotype was observed with N74D and P90A CA mutants in terms of type I IFN hypersensitivity and resistance to MxB. 2019 Journal of virology Discussion HIV N74D;P90A 38;47 42;51 Capsid 52 54 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. also proposed that inappropriate uncoating kinetics might account for the higher type I IFN sensitivity of the N74D virus. 2019 Journal of virology Discussion HIV N74D 111 115 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Considering the roles of the G94D/G116R mutations for the RGDA/Q112D virus, we speculate that the G94D mutation is responsible for conferring IFN-beta resistance to the RGDA/Q112D virus, whereas the G116R mutation is a compensatory mutation to rescue the infectivity of the RGDA/Q112D+G94D virus. 2019 Journal of virology Discussion HIV G116R;G116R;G94D;G94D;G94D;Q112D;Q112D;Q112D 34;199;29;98;285;63;174;279 39;204;33;102;289;68;179;284 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Consistent with this finding, we failed to detect IFNs in the culture supernatants of Jurkat cells infected with either WT or RGDA/Q112D viruses (data not shown). 2019 Journal of virology Discussion HIV Q112D 131 136 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. CPSF6 is a host factor that is capable of modulating the type I IFN sensitivity of HIV-1 since CPSF6 binding-deficient CA mutant N74D virus was shown to be hypersensitive to type I IFN in myeloid cell line THP-1 cells. 2019 Journal of virology Discussion HIV N74D 129 133 Capsid 119 121 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. CypA binding is another factor that possibly affects the type I IFN sensitivity of HIV-1, since CypA binding-deficient CA mutant P90A was shown to be hypersensitive to type I IFN in THP-1 cells. 2019 Journal of virology Discussion HIV P90A 129 133 Capsid 119 121 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Despite its hypersensitivity to type I IFN, the RGDA/Q112D virus was, paradoxically, resistant to MxB. 2019 Journal of virology Discussion HIV Q112D 53 58 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. For instance, the N74D and E45A mutations appear to directly decrease the rate of uncoating without any impact on the kinetics of reverse transcription. 2019 Journal of virology Discussion HIV E45A;N74D 27;18 31;22 RT 130 151 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. However, the frequency of each type of CA mutation in the adapted viruses was not very high (only 30%, 5%, and 10% for the RGDA/Q112D+Q4R, RGDA/Q112D+G94D, and RGDA/Q112D+G94D/G116R mutations, respectively). 2019 Journal of virology Discussion HIV G116R;G94D;Q112D;G94D;Q112D;Q112D;Q4R 176;171;165;150;128;144;134 181;175;170;154;133;149;137 Capsid 39 41 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Importantly, these CA mutations were sufficient to reverse the IFN-beta hypersensitivity of the RGDA/Q112D parental virus. 2019 Journal of virology Discussion HIV Q112D 101 106 Capsid 19 21 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In addition to the aforementioned mutations in CA, we have identified an A15T mutation in Nef of IFN-beta-resistant viruses that warrants further investigation (data not shown). 2019 Journal of virology Discussion HIV A15T 73 77 Nef;Capsid 90;47 93;49 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the IFN-beta resistance obtained by the G94D/G116R mutation was clearly achieved through a different mechanism because the kinetics of the completion of reverse transcription were delayed relative to those in the WT virus only in the presence of IFN-beta. 2019 Journal of virology Discussion HIV G116R;G94D 58;53 63;57 RT 166 187 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the Q4R mutation enhanced the sensitivity of the RGDA/Q112D virus to MxB, despite the higher IFN-beta resistance of the RGDA/Q112D+Q4R virus. 2019 Journal of virology Discussion HIV Q112D;Q112D;Q4R;Q4R 67;138;17;144 72;143;20;147 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In contrast, the RGDA/Q112D+G94D/G116R mutation induces a change in reverse transcription only in the presence of IFN-beta, with the kinetics of reverse transcription being slower in the RGDA/Q112D+G94D/G116R virus than in the WT virus. 2019 Journal of virology Discussion HIV G116R;G116R;G94D;G94D;Q112D;Q112D 33;203;28;198;22;192 38;208;32;202;27;197 RT;RT 68;145 89;166 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In this study, we demonstrate that two types of CA mutations were sufficient to confer IFN-beta resistance to the RGDA/Q112D virus. 2019 Journal of virology Discussion HIV Q112D 119 124 Capsid 48 50 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. In this study, we utilized the RGDA/Q112D virus, which is hypersensitive to IFN-beta, to investigate how the HIV-1 capsid can evade type I IFN-mediated restriction. 2019 Journal of virology Discussion HIV Q112D 36 41 Capsid 115 121 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Interestingly, the effect of the G94D/G116R mutations was reproduced even in the WT virus. 2019 Journal of virology Discussion HIV G116R;G94D 38;33 43;37 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Interestingly, the virus acquiring the Q4R mutation took the indirect route to evade enhanced IFN-beta sensitivity by accelerating the process of reverse transcription, which subsequently accelerated the initiation of uncoating. 2019 Journal of virology Discussion HIV Q4R 39 42 RT 146 167 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It appeared that the RGDA/Q112D virus acquired two variants that differently changed CPSF6 binding. 2019 Journal of virology Discussion HIV Q112D 26 31 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It is notable that the kinetics of the completion of reverse transcription by the RGDA/Q112D virus were delayed relative to those in the WT only in the presence of IFN-beta. 2019 Journal of virology Discussion HIV Q112D 87 92 RT 53 74 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It is possible that these cyclophilins are involved in IFN-beta-mediated inhibition of the RGDA/Q112D virus in T cells. 2019 Journal of virology Discussion HIV Q112D 96 101 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It is reasonable to assume that the Q4R mutation arising during adaptation in IFN-beta-treated cells might be specifically related to the RGDA/Q112D virus, whereas the effect of the G94D/G116R mutations was reproduced even in the WT virus. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D;Q4R 187;182;143;36 192;186;148;39 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It is reasonable to speculate that the Q4R and G94D mutations are specifically associated with the RGDA/Q112D virus. 2019 Journal of virology Discussion HIV G94D;Q112D;Q4R 47;104;39 51;109;42 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. It may be reasonable to speculate that, in addition to the G116R mutation in CA. 2019 Journal of virology Discussion HIV G116R 59 64 Capsid 77 79 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Moreover, the RGDA/Q112D+G94D/Q116R mutation did not alter the kinetics of the initiation of uncoating relative to those in the WT virus. 2019 Journal of virology Discussion HIV G94D;Q112D;Q116R 25;19;30 29;24;35 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Notably, the Q4R mutation drastically altered multiple CA properties, including the acceleration of the kinetics of the completion of reverse transcription and the initiation of uncoating relative to those in WT HIV, in the presence or absence of IFN-beta. 2019 Journal of virology Discussion HIV Q4R 13 16 RT;Capsid 134;55 155;57 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Our results demonstrate that neither of the CA mutations that arose during adaptation of the RGDA/Q112D virus in IFN-beta-treated cells restored the CypA binding of the RGDA/Q112D virus. 2019 Journal of virology Discussion HIV Q112D;Q112D 98;174 103;179 Capsid 44 46 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Overall, the data generated in this study demonstrate that the IFN-beta-hypersensitive RGDA/Q112D virus can evolve to be IFN-beta resistant with two distinct variants: a virus with the single Q4R mutation in CA or a virus with the double substitutions G94D/G116R in CA. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D;Q4R 257;252;92;192 262;256;97;195 Capsid;Capsid 208;266 210;268 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. proposed that cyclophilins other than CypA are involved in HIV-1 sensitivity to type I IFN, as CsA treatment of THP-1 cells rescued the impaired infectivity of the P90A virus in IFN-alpha-treated cells. 2019 Journal of virology Discussion HIV P90A 164 168 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The G94D/G116R mutations do not change the sensitivity of the RGDA/Q112D virus to MxB. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D 9;4;67 14;8;72 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The impact of the Nef A15T mutation needs to be elucidated in future studies. 2019 Journal of virology Discussion HIV A15T 22 26 Nef 18 21 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The impact of these mutations allowing IFN-beta resistance was obvious, as the RGDA/Q112D viruses harboring these mutations were even more IFN-beta resistant than the WT virus in a single-cycle infection assay. 2019 Journal of virology Discussion HIV Q112D 84 89 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The opposite effect on the CPSF6-358 sensitivity of the RGDA/Q112D virus was observed with the other adaptive change, the G94D/G116R mutations. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D 127;122;61 132;126;66 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The other G94D/G116R mutation overcoming IFN-beta sensitivity clearly utilizes a distinct mechanism. 2019 Journal of virology Discussion HIV G116R;G94D 15;10 20;14 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The phenotype of the virus with the Q4R mutation shows us that accelerated reverse transcription and initiation of uncoating are clearly a potential mechanism to avoid IFN-beta sensitivity targeting the core as a PAMP. 2019 Journal of virology Discussion HIV Q4R 36 39 RT 75 96 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R and G94D/G116R mutations also impacted the interaction with the known cellular factors CPSF6 and MxB in a different manner. 2019 Journal of virology Discussion HIV G116R;G94D;Q4R 17;12;4 22;16;7 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The Q4R mutation changes the CA properties of the RGDA/Q112D virus, including sensitivity to MxB and CPSF6-358, compared with those of the RGDA/Q112D virus. 2019 Journal of virology Discussion HIV Q112D;Q112D;Q4R 55;144;4 60;149;7 Capsid 29 31 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D virus evolved to be IFN-beta resistant, with two distinct variants differently affecting the sensitivity of the RGDA/Q112D virus to MxB. 2019 Journal of virology Discussion HIV Q112D;Q112D 9;132 14;137 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D virus lost its CypA binding ability and exhibited enhanced IFN-beta sensitivity, consistent with a potential role of CypA in reducing sensitivity to type I IFNs. 2019 Journal of virology Discussion HIV Q112D 9 14 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The RGDA/Q112D virus was even more resistant to MxB than the N74D virus in our experimental settings. 2019 Journal of virology Discussion HIV N74D;Q112D 61;9 65;14 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. The single Q4R mutation or the double substitutions G94D/G116R in CA which emerged in this adaptation conferred IFN-beta resistance to the IFN-beta-hypersensitive RGDA/Q112D mutant virus. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D;Q4R 57;52;168;11 62;56;173;14 Capsid 66 68 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These findings further support the hypothesis that HIV-1 isolates with the Q4R and G94D/G116R mutations have different mechanisms to overcome their sensitivity to type I IFNs. 2019 Journal of virology Discussion HIV G116R;G94D;Q4R 88;83;75 93;87;78 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. These results suggest that MxB does not contribute to the IFN-beta sensitivity of the RGDA/Q112D virus in T cells, and these findings are similar to those of previous studies that suggested a limited role of MxB in restriction mediated by type I IFN in myeloid THP-1 cells. 2019 Journal of virology Discussion HIV Q112D 91 96 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. This evolution of the RGDA/Q112D virus in IFN-beta-treated cells is of interest since the G94D mutation is detrimental to the infectivity of the RGDA/Q112D virus. 2019 Journal of virology Discussion HIV G94D;Q112D;Q112D 90;27;150 94;32;155 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. This Q4R mutation in the RGDA/Q112D derivative changed the intrinsic properties of the virus to accelerate reverse transcription and the initiation of uncoating in the presence or absence of IFN-beta. 2019 Journal of virology Discussion HIV Q112D;Q4R 30;5 35;8 RT 107 128 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. This result may imply that the RGDA/Q112D virus was under strong evolutionary pressure to select for the G94D mutation to facilitate IFN-beta resistance, even if the mutation is harmful for its infectivity. 2019 Journal of virology Discussion HIV G94D;Q112D 105;36 109;41 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. This RGDA/Q112D+Q4R mutation accelerates reverse transcription kinetics and the timing of the initiation of uncoating in an IFN-beta-independent manner. 2019 Journal of virology Discussion HIV Q112D;Q4R 10;16 15;19 RT 41 62 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. Thus, the influence of the G94D/G116R mutations on IFN-beta resistance was not specific to the RGDA/Q112D virus. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D 32;27;100 37;31;105 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We are interested in why the noninfectious RGDA/Q112D+G94D virus represented 5% of all viruses. 2019 Journal of virology Discussion HIV G94D;Q112D 54;48 58;53 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We identified two different pathways of resistance which involve either the Q4R change or the G94D/G116R changes in the CA after adaptation of the RGDA/Q112D virus in IFN-beta-treated cells. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D;Q4R 99;94;152;76 104;98;157;79 Capsid 120 122 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. We observed that the IFN-beta-hypersensitive RGDA/Q112D virus was less sensitive to CPSF6-358 inhibition than the WT virus and that this change was restored by the Q4R mutation to a level of that of the WT virus. 2019 Journal of virology Discussion HIV Q112D;Q4R 50;164 55;167 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. While the sensitivity of the RGDA/Q112D virus to MxB and CPSF6-358 was enhanced only by the Q4R mutation, neither the Q4R mutation nor the G94D/G116R mutations allowed the recovery of the deficient CypA binding of the RGDA/Q112D virus. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D;Q112D;Q4R;Q4R 144;139;34;223;92;118 149;143;39;228;95;121 31511380 Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid. While we were able to demonstrate that the Q4R and G94D/G116R mutations conferred partial IFN-beta resistance to the RGDA/Q112D virus in THP-1 cells. 2019 Journal of virology Discussion HIV G116R;G94D;Q112D;Q4R 56;51;122;43 61;55;127;46 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. In support of this strategy, CH505.N279K.G458Y SOSIP/GnT1-, which has 9 nM affinity for CH235 UCA2 (Fig 2, S3 Fig), induces CH235 early precursors in CH235 UCA2 knock-in mice, overcoming an improbable K19T heavy chain mutation; whereas CH505.N279K gp120, which has low affinity for CH235 UCA2, did not induce these precursors (Saunders et al., submitted). 2019 PLoS pathogens Discussion HIV G458Y;K19T;N279K;N279K 41;201;35;242 46;205;40;247 gp120 248 253 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. Interactions between the side chain of the gp120 loop D residue K279 with the CH235 UCA2 CDR L3, as well as with other gp120 regions (Fig 3C, S5C Fig), suggested a role for the N279K mutation in stabilizing the loop D structure and enabling its interactions with the CH235 UCA2 CDR L3. 2019 PLoS pathogens Discussion HIV N279K 177 182 gp120;gp120 43;119 48;124 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. N279K and G458Y confer resistance to VRC01-class bnAbs, such as VRC01 and 3BNC117, but do not impart resistance to mature CH103 and CH235/CH235.12 in the context of CH505TF (Fig 1). 2019 PLoS pathogens Discussion HIV G458Y;N279K 10;0 15;5 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The barrier to neutralization by CH235 UCA2 was overcome by synergistic interactions between two Env mutations, one in loop D (N279K, which does not remove an N-glycan) and another in V5 (G458Y). 2019 PLoS pathogens Discussion HIV G458Y;N279K 188;127 193;132 Env 97 100 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. The fact that N279K does not remove an N-glycan reduces the possibility of eliciting a strain-specific glycan-hole response to this site. 2019 PLoS pathogens Discussion HIV N279K 14 19 31527908 Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. These structural results show how the N279K and the G458Y mutations synergize to stabilize Env interactions with the CDR L3 loop of CH235 UCA2, and enable the binding of CH235 UCA2 to the CH505TF.N279K.G458Y Env. 2019 PLoS pathogens Discussion HIV G458Y;G458Y;N279K;N279K 52;202;38;196 57;207;43;201 Env;Env 91;208 94;211 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. Although there is no indication of a significant, underlying trend, it should be noted that instances of E138A doubled in 2010-2013 compared to 2007-2009, which could be a result of increasing INSTI usage. 2019 Heliyon Discussion HIV E138A 105 110 INSTI 193 198 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. Atripla was commonly prescribed since its approval by the US Food and Drug Administration (FDA) in 2006, and its widespread use likely led to the preeminence of NNRTI TDR (K103N in particular). 2019 Heliyon Discussion HIV K103N 172 178 NNRTI 161 166 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. E138A is an accessory mutation that confers major resistance to RAL and EVG in combination with Q148 mutations. 2019 Heliyon Discussion HIV E138A 0 5 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. Further, a review of K65R suggested that the mutation is uncommon, and individuals infected with subtype C HIV may be at a greater risk of acquiring the mutation. 2019 Heliyon Discussion HIV K65R 21 25 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. Interestingly, we would expect the subsequent appearance of TDF/FTC-associated mutations, but we only observed one case of M184V in 2006 and zero cases of K65R, which are major NRTI mutations selected for by FTC/3TC and TDF, respectively. 2019 Heliyon Discussion HIV K65R;M184V 155;123 159;128 NRTI 177 181 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. The low prevalence of PI TDR and the predominance of L90M among PI TDRMs is consistent with other US-based studies. 2019 Heliyon Discussion HIV L90M 53 57 PI;PI 22;64 24;66 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. This may be due to the lower selectivity of FTC for M184V and the inhibitive action of M184V and K65R on viral fitness. 2019 Heliyon Discussion HIV K65R;M184V;M184V 97;52;87 101;57;92 31535044 Surveillance of transmitted HIV drug resistance among newly diagnosed, treatment-naive individuals at a county HIV clinic in Santa Clara County. Unfortunately, we were unable to fully characterize the HIV subtypes of our study sample, so it is unclear if the absence of K65R in our study is related to our subtype distribution. 2019 Heliyon Discussion HIV K65R 125 129 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A related change, R41K, is a common polymorph (26% in subtype B and 68% of all Gag genes in the LANL database), and may be involved in the emergence of protease resistance to an investigational protease inhibitor. 2019 PloS one Discussion HIV R41K 18 22 PR;PR;Gag 152;194;79 160;202;82 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A V370M containing virus was previously shown to be sensitive to GSK3532795 (FC = 2.8), so it is not surprising that this participant had a good clinical response (viral load reduction = -1.69 log10). 2019 PloS one Discussion HIV V370M 2 7 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. A364V rarely is found in the LANL database in any subtype, however, in vitro selection for bevirimat resistance from wild-type virus yielded this substitution, and A364V was also reported in two HIV-1-infected participants in a bevirimat clinical trial. 2019 PloS one Discussion HIV A364V;A364V 164;0 169;5 HIV infections 195 209 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Although neither V362I nor V370A single changes significantly altered susceptibility to GSK3532795 (2-fold for each virus), the V362I/V370A combination resulted in a 208-fold reduction in GSK3532795 sensitivity. 2019 PloS one Discussion HIV V362I;V362I;V370A;V370A 17;128;27;134 22;133;32;139 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. An example in this regard is R286K, which by itself only showed a 2.5-FC in a site-directed mutant, while a double mutant with V362I induced a 61-FC. 2019 PloS one Discussion HIV R286K;V362I 29;127 34;132 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Another participant (# 44) started out with a wild type genotype but had an emergent V370M on Day 11 with a FC = 116. 2019 PloS one Discussion HIV V370M 85 90 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. As previously noted, double polymorphic viruses such as V362I/V370A were selected in vitro and observed in the clinic. 2019 PloS one Discussion HIV V362I;V370A 56;62 61;67 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. As reported for A364V, its relative rate of cleavage at CA/SP1 by HIV-1 protease was 9.7-fold elevated vs wild type virus. 2019 PloS one Discussion HIV A364V 16 21 PR;SP1;Capsid 72;59;56 80;62;58 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Both helix 10 and the beta-turn are close to residue 362 in the model, and mutations of A326 or T332, in combination with the V362I mutation may serve to destabilize the immature CA/SP1 assembly. 2019 PloS one Discussion HIV V362I 126 131 SP1;Capsid 182;179 185;181 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Further, addition of A326T to the duo induced a 437-FC (Table 4). 2019 PloS one Discussion HIV A326T 21 26 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. H219Q is found in the CypA binding loop and was shown in to increase the RC of the poorly growing V362I/V370A virus from 60% to 115%. 2019 PloS one Discussion HIV V362I;V370A;H219Q 98;104;0 103;109;5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. H219Q was another secondary mutation observed in vitro. 2019 PloS one Discussion HIV H219Q 0 5 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In addition to V362I and A364V, a number of secondary mutations were selected. 2019 PloS one Discussion HIV A364V;V362I 25;15 30;20 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In our experiments, virus populations that acquired A364V had greatly reduced GSK3532795 susceptibility and this was confirmed by the single A364V site-directed mutant, which had 835-fold reduced GSK3532795 susceptibility but maintained a RC of 82%. 2019 PloS one Discussion HIV A364V;A364V 52;141 57;146 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In two in vitro passage experiments, the V362I was replaced with A364V, conferring a larger reduction in GSK3532795 susceptibility and better replication and suggesting that V362I alone in Gag produces an unfit virus. 2019 PloS one Discussion HIV A364V;V362I;V362I 65;41;174 70;46;179 Gag 189 192 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. In vitro, the addition of T332S, A326T or R286K to V362I increased the fold-reduction in GSK3532795 EC50 from 2.2 to 5.7, 12, and 61-fold, respectively. 2019 PloS one Discussion HIV A326T;R286K;T332S;V362I 33;42;26;51 38;47;31;56 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Interestingly, one subject (# 22) with baseline R286K/V370M and BL FC of 1.6 acquired the Q369Q/H mixture on dosing, displayed a reduced susceptibility at Day 11 compared to baseline (FC = 12) and exhibited a virologic response of -0.93 log10 RNA. 2019 PloS one Discussion HIV Q369H;Q369Q;R286K;V370M 90;90;48;54 97;97;53;59 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Of note, subtype B contains 4.3% of the R286K/V370A double polymorphism and in the clinical study, one subject with a baseline R286K (FC 3.9) acquired a V370A/V mixture during dosing and displayed emergent resistance on-therapy (FC 15.8). 2019 PloS one Discussion HIV R286K;R286K;V370A;V370A;V370V 40;127;46;153;153 45;132;51;160;160 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. R41G emerged alongside V362I/T332S in vitro and was shown to increase the GSK3532795 resistance of this double variant from 5.7- to 217-fold. 2019 PloS one Discussion HIV T332S;V362I;R41G 29;23;0 34;28;4 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. R41G is present in 1/3083 isolates in the LANL database and is not a primary PI resistance substitution. 2019 PloS one Discussion HIV R41G 0 4 PI 77 79 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. R41G might alter the dynamics of the loop motion and the final positioning of the loop, which could cause the active site to better recognize V362I variants such as V362I/T332S. 2019 PloS one Discussion HIV T332S;V362I;V362I;R41G 171;142;165;0 176;147;170;4 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Secondary substitutions selected in vitro mapped to three locations, the CA-CTD (R286K, A326T, T332S and I333V), the cyclophilin A (CypA) binding domain of Gag (V218/A/M, H219Q and G221E), and protease (R41G). 2019 PloS one Discussion HIV A326T;G221E;H219Q;I333V;R286K;R41G;T332S 88;181;171;105;81;203;95 93;186;176;110;86;207;100 PR;Gag;Capsid 193;156;73 201;159;75 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Similar to what was observed in vitro, doses of 10-120 mg of GSK3732795 primarily selected at Day 10 for emergent substitutions (or selection from a mixture at baseline) at 2 positions, V362I (N = 7/18 participants) and A364V (N = 6/18), with 3 of these participants (#s 1, 26 and 80) selecting both changes. 2019 PloS one Discussion HIV A364V;V362I 220;186 225;191 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Similarly, V362I/V370A also demonstrated an elevated cleavage rate (4.9-fold) and both viruses showed less than 100% maximal inhibition (MPI) by GSK3532795. 2019 PloS one Discussion HIV V362I;V370A 11;17 16;22 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. The results of all these experiments produced similar resistance substitutions, with A364V and V362I being predominantly selected, although the V362I mutation needs to be present in conjunction with other polymorphisms, such as V370A, in order to greatly reduce susceptibility to GSK3732795 in vitro. 2019 PloS one Discussion HIV A364V;V362I;V362I;V370A 85;95;144;228 90;100;149;233 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. These substitutions are close to (V362I) or adjacent to (A364V) the HIV-1 protease cleavage site (L363/A364) that is inhibited by the action of GSK3532795. 2019 PloS one Discussion HIV A364V;V362I 57;34 62;39 PR 74 82 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. This substitution was generally associated with smaller reductions in GSK3532795 susceptibility and the single V362I site-directed mutant remained susceptible to GSK3532795. 2019 PloS one Discussion HIV V362I 111 116 31622432 Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. V362I is a polymorphism in subtype B isolates (15.4% in the LANL database), and, depending on background, is associated with bevirimat resistance. 2019 PloS one Discussion HIV V362I 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Additionally, several V3 loop mutants that are similar to those identified in other resistance selections were found in some of our sequences (S306R, T319A). 2019 Retrovirology Discussion HIV S306R;T319A 143;150 148;155 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Additionally, we did not identify any overlap of our specific compensatory mutations with those found in the other entry-inhibitor resistance screens with Q577R virus. 2019 Retrovirology Discussion HIV Q577R 155 160 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Additionally, within the > 50,000 non-Group O sequences from the Los Alamos HIV Sequence Database, ~ 1.4% contain Q577R. 2019 Retrovirology Discussion HIV Q577R 114 119 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Against N-trimer peptides N44, N36, and IZN36, the C-peptide T2635, and the retrocyclin RC-101, Q577R is found in some or all of the resistant viruses and always accompanied by other gp41 mutation(s). 2019 Retrovirology Discussion HIV Q577R 96 101 gp41 183 187 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Although none of our specific compensatory mutations are found in Q577R viruses resistant to other entry inhibitors, it seems likely that similar compensation mechanisms are used. 2019 Retrovirology Discussion HIV Q577R 66 71 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Although our nucleotide sequences differ from that in the Legiewicz study (codon CGG for Q577R and AAC for Q577N), we similarly postulate an RRE structural rearrangement centered at the base of stem-loop V, the location of the 577 codon, that likely contributes to the fitness defect. 2019 Retrovirology Discussion HIV Q577N;Q577R 107;89 112;94 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. As shown in an alignment of the ~ 750 Group M primary isolate Q577R Envs (out of > 50,000 Group M sequences from the Los Alamos HIV Sequence Database) with our PIE12-trimer resistant sequences, none of the candidate PIE12-trimer-resistant compensatory mutations are prevalent in the primary isolates (Additional file 4). 2019 Retrovirology Discussion HIV Q577R 62 67 Env 68 72 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. By itself, Q577R provided only modest resistance to the N-trimer and C-peptide inhibitors (< threefold). 2019 Retrovirology Discussion HIV Q577R 11 16 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Consistent with our results, many of these studies have demonstrated a fitness defect for Q577R. 2019 Retrovirology Discussion HIV Q577R 90 95 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Efforts are underway to discover novel d-peptide entry inhibitors that maintain high affinity to both the native and Q577R pockets. 2019 Retrovirology Discussion HIV Q577R 117 122 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. For example, the uncommon Group O HIV-1 strains (< 1% of global HIV-1 infections) primarily contain Q577R. 2019 Retrovirology Discussion HIV Q577R 100 105 HIV infections 64 80 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. have investigated the effect of Q577R on Env structure and function. 2019 Retrovirology Discussion HIV Q577R 32 37 Env 41 44 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. However, there is little overlap between the Env modifications seen in our pools and those in naturally occurring strains with Q577R and in Q577R virus resistant to other entry inhibitors. 2019 Retrovirology Discussion HIV Q577R;Q577R 127;140 132;145 Env 45 48 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Importantly, Q577R Env (HXB2 strain) has been shown to be properly expressed, processed, and incorporated into pseudovirions, so the fitness defect is likely downstream of virus production. 2019 Retrovirology Discussion HIV Q577R 13 18 Env 19 22 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. In previous entry inhibitor resistance studies that include Q577R and for which gp120 sequence is available, compensatory mutations are found in CD4 binding residues (E426K), the V1/V2 loop (D167N), and in the V3 loop (R298K, S306G, I309M, T319I, and E322D), indicating that changes to gp120-based fusion determinants, such as CD4 and co-receptor binding, help restore gp41-based fitness defects. 2019 Retrovirology Discussion HIV D167N;E322D;E426K;I309M;Q577R;R298K;S306G;T319I 191;251;167;233;60;219;226;240 196;256;172;238;65;224;231;245 gp120;gp120;gp41 80;286;369 85;291;373 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Indeed, our data demonstrate only modest differences in C-peptide inhibition of Q577R compared to WT pseudoviruses, including C34, T20 (enfuvirtide) and T1249 (Additional file 3), and our PIE12-trimer resistant pools retain sensitivity to a related peptide, C37 (Table 1). 2019 Retrovirology Discussion HIV Q577R 80 85 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Interestingly, Q550H and Q577R/N/K are observed in nearly all PIE12-trimer resistant sequences. 2019 Retrovirology Discussion HIV Q550H;Q577K;Q577N;Q577R 15;25;25;25 20;34;34;34 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Q577R has also been identified in viral resistance screens against other HIV-1 entry inhibitors that target the prehairpin intermediate. 2019 Retrovirology Discussion HIV Q577R 0 5 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Residue 583 is variable in the Q577R-containing primary isolates, although only hydrophobic residues (valine, isoleucine, leucine, and methionine) are observed. 2019 Retrovirology Discussion HIV Q577R 31 36 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Surprisingly, genetic analysis of the virus from a patient resistant to the FDA-approved peptide fusion inhibitor enfuvirtide also identified the Q577R mutation, and in the context of that patient's pre-treatment env, provided 25-fold resistance to enfuvirtide. 2019 Retrovirology Discussion HIV Q577R 146 151 Env 213 216 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. The presence of additional mutations within the RRE, namely Q550H and a silent mutation at V583(GTG GTA), suggest these may play an important compensatory role in restructuring the RRE. 2019 Retrovirology Discussion HIV Q550H 60 65 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. They have shown that the Q577R substitution leads to: (1) a more stable 6-helix bundle structure, (2) greater neutralization sensitivity to CD4 mimetics, and (3) decreased susceptibility to CD4-induced gp41 conformational changes that lead to viral inactivation. 2019 Retrovirology Discussion HIV Q577R 25 30 gp41 202 206 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. This discovery is an outlier, however, as the primary resistance mechanism to enfuvirtide involves mutation within gp41 residues 547-556, and the enfuvirtide sensitivity of other studied HIV-1 strains is minimally affected by Q577R. 2019 Retrovirology Discussion HIV Q577R 226 231 gp41 115 119 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. This study identifies Q577R/N/K within the gp41 N-trimer hydrophobic pocket as the primary resistance mechanism used to escape inhibition by the highly potent d-peptide entry inhibitor PIE12-trimer. 2019 Retrovirology Discussion HIV Q577K;Q577N;Q577R 22;22;22 31;31;31 gp41 43 47 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Three Rev mutations (env positions 2354, 2375 and 2435, leading to N86Y, G93W, and G113R in Rev while silent in Env) surfaced in our initial analysis (Additional file 1), but each is present in only one resistant pool, none are fully penetrant, and all are located in the predicted disordered nuclear export sequence. 2019 Retrovirology Discussion HIV G113R;G93W;N86Y 83;73;67 88;77;71 Rev;Rev;Env;Env 6;92;21;112 9;95;24;115 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. Viral escape from a recently identified adnectin, 6200_A08, which similarly targets the gp41 hydrophobic pocket, has also been shown to use Q577R as the primary mechanism. 2019 Retrovirology Discussion HIV Q577R 140 145 gp41 88 92 31640718 Characterization of resistance to a potent D-peptide HIV entry inhibitor. With its improved potency, chol-PIE12-trimer is better able to combat PIE12-trimer resistant virus and inhibits pseudovirions with the Q577R mutation with a low nanomolar IC50. 2019 Retrovirology Discussion HIV Q577R 135 140 31651864 HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. M184V/I may alter the optimal binding of NRTIs and decrease 3TC removal and enzymatic processivity, and results in drug resistance. 2019 Medicine Discussion HIV M184I;M184V 0;0 7;7 NRTI 41 46 31651864 HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. M184V/I was the most common NRTI-related mutation, which might be due to the frequent use of Lamivudine (3TC) in ART, and 3TC resistance mutation M184V/I was highly prevalent in HIV-1 infected patients. 2019 Medicine Discussion HIV M184I;M184I;M184V;M184V 0;146;146;0 7;153;153;7 NRTI 28 32 HIV infections 178 192 31651864 HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. We observed that K103N/KN, V106M/MA/MV, G190A/AG/S, and Y188L/C are the major NNRTI-related mutations in China and other countries, which may be the result of the wide-spread use of NNRTIs. 2019 Medicine Discussion HIV G190A;G190G;G190S;K103K;K103N;V106A;V106M;V106V;Y188C;Y188L 40;40;40;17;17;27;27;27;56;56 50;50;50;25;24;38;38;38;63;63 NNRTI;NNRTI;Matrix 78;182;33 83;188;35 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. A recent subgroup analysis of this study showed that the response rate of DTG also was high when 3TC or FTC was used in the presence of a M184V/I mutation. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 138;138 145;145 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Although most were small trials (less than 500 patients) originating from single cohorts, they all described low VF rates, irrespective of the presence of the M184V/I mutation. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 159;159 166;166 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Although the unweighted univariate analysis showed that M184V/I had a significant effect on the increase of the risk of the composite outcome, including both VBs and VF, this effect was no longer statistically significant in the IPW analysis. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 56;56 63;63 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Furthermore, among 126 patients treated with a 3TC/DTG-containing regimen and followed for a median of 1.3 years, VF was detected in none of 21 patients with the M184V/I mutation and in 2 of 105 patients without the mutation. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 162;162 169;169 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. In both studies, no VF was detected in 59 and 27 patients, respectively, who switched to a DTG-based regimen, despite a high M184V/I prevalence (100% in the first study, 63% in the latter). 2019 Open forum infectious diseases Discussion HIV M184I;M184V 125;125 132;132 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. In conclusion, in this large international prospective study, we found an extremely low rate of VF among treatment-experienced patients receiving an ABC/3TC/DTG regimen, irrespective of the presence of a M184V/I mutation. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 204;204 211;211 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. In the study by Gagliardini et al, the 3-year probability to remain VF-free among treatment-experienced patients on PI- or DTG-based dual therapy containing lamivudine in the presence or absence of the M184V/I mutation was 87.8% and 91.9%, respectively (P = .32). 2019 Open forum infectious diseases Discussion HIV M184I;M184V 202;202 209;209 PI 116 118 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. In this multi-cohort study, the characteristics of the groups of patients with or without M184V/I were too divergent to allow the use of a standard multivariate Cox proportional-hazards analysis. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 90;90 97;97 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Indeed, precise information about adherence to ART was only available for a small part of the data set and patients with or without emergence of the M184V/I mutation after VF may have had a different behavior with regards to treatment adherence. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 149;149 156;156 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Of note, M184V/I was present at baseline in more than 80% of patients and 3TC or emtricitabine (FTC) was included as part of the backbone in both arms of the trial. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 9;9 16;16 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Other integrase strand transfer inhibitors, such as elvitegravir in the co-formulation elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, showed in a prospective open-label study to be effective in maintaining viral suppression at week 12, despite archived M184V/I mutations. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 267;267 274;274 IN 6 15 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Overall, we observed a very low VF rate (1.3%) after the switch to ABC/3TC/DTG, with no statistically significant difference in the VF incidence among patients with or without M184V/I after correction for differences in patient characteristics. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 176;176 183;183 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Previous studies have addressed the effect of the M184V/I mutation on the efficacy of a DTG-containing regimen. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 50;50 57;57 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Similar results were found in more recent studies where DTG plus 1 to 2 NRTIs were noninferior to PI-based therapy, regardless of the presence of the M184V/I mutation and other NRTI mutations at 48 and 78 weeks. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 150;150 157;157 NRTI;NRTI;PI 72;177;98 77;181;100 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. To the best of our knowledge, this study is the largest observational study to focus on the impact of the M184V/I mutation on the risk of VF in virologically-suppressed patients switching to ABC/3TC/DTG. 2019 Open forum infectious diseases Discussion HIV M184I;M184V 106;106 113;113 31660328 Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. We showed with the IPW analysis that the M184V/I mutation had no statistically significant effect on VF, including when using the composite outcome (although a trend could not be excluded). 2019 Open forum infectious diseases Discussion HIV M184I;M184V 41;41 48;48 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. It consisted of glutamine (Q) substitution by aspartic acid (D) at position 621 (Q621D). 2019 Viruses Discussion HIV D621D;Q621D 43;81 82;86 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. It would be interesting to conduct phenotypic studies to further evaluate the role of isoleucine substitution in viral Env function (R841I) including others frequents mutations. 2019 Viruses Discussion HIV R841I 133 138 Env 119 122 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The current study identified and highly selection of the isoleucine (K6I) associated to chronic compared to TF viruses (Figure 6, Table 1). 2019 Viruses Discussion HIV K6I 69 72 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The first important point mutation identified consisted of substitution of an arginine (R) by an isoleucine (I) at position 959 of alignment and referred to HXB2 numbering to position 841 (R841I; Figure 5). 2019 Viruses Discussion HIV R841I 189 194 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The mutations patterns associated with chronic viruses consisted of glutamic acid (E) at position 153 in the V1 loop (153E), a methionine (M) substitution by isoleucine at position 24 in the signal peptide (M24I) and aspartic acid (D) substitution by a valine (V) in the cytoplasmic tail (D751V; Figure 7, Figure 9 and Figure 10 and Table 2). 2019 Viruses Discussion HIV D751V;E153E;M24I 289;65;207 294;104;211 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The R841I signature associated to clade B HIV-1 TF viruses was localized at position 841 of the GP41 cytoplasmic tail in this LLP-1. 2019 Viruses Discussion HIV R841I 4 9 gp41 96 100 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The R841I substitution identified in the acute stage of infection of our study may constitute a key factor to enhance LLP-1 functions. 2019 Viruses Discussion HIV R841I 4 9 31683782 HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses. The second important amino acid signature identified was K6I (within the signal peptide), highly enriched in chronic vs. 2019 Viruses Discussion HIV K6I 57 60 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. We validated 8 of these polymorphisms, including 2 well-characterized CD8+ T cell escape mutations, K94E and H116N, using site-directed mutagenesis. 2019 Cell reports Discussion HIV H116N;K94E 109;100 114;104 31693887 Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity. While mechanisms responsible for impaired SERINC5 internalization by primary nef alleles or mutants have not been defined in this study, it is intriguing that K94E and H116N had only modest effects on Nef's ability to downregulate CD4 or HLA class I, suggesting that K94 and H116 lie within domains of Nef that are particularly important to antagonize SERINC5 rather than to internalize CD4 or HLA. 2019 Cell reports Discussion HIV H116N;K94E 168;159 173;163 Nef;Nef;Nef 77;201;302 80;204;305 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Despite stabilizing Pr55Gag, virions obtained with the Nef-G2A mutant were poorly infectious. 2019 Frontiers in microbiology Discussion HIV G2A 59 62 Nef;PR 55;20 58;22 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Indeed, Nef promotes HDAC6 degradation without the need to be membrane-anchored for Nef or to be a plasma membrane protein for HDAC6, as results with the Nef-G2A mutant indicate. 2019 Frontiers in microbiology Discussion HIV G2A 158 161 Nef;Nef;Nef 8;84;154 11;87;157 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Nef-G2A-mediated HDAC6 degradation and co-immunoprecipitation, observed in this work, point to this direction. 2019 Frontiers in microbiology Discussion HIV G2A 4 7 Nef 0 3 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. We have reported that Nef-induced disruption of the endocytic recycling compartment (ERC) is also lost with the Nef-EA(E160A) mutation. 2019 Frontiers in microbiology Discussion HIV E160A 119 124 Nef;Nef 22;112 25;115 31736889 HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. We observed that the antiviral HDAC6 functions were only neutralized by wt-Nef and Nef mutants able to target HDAC6, such Nef-G2A and Nef-EA, whereas mutants that cannot target HDAC6, such as Nef-PPAA and Nef-LLAA, are unable to restore efficient viral production. 2019 Frontiers in microbiology Discussion HIV G2A 126 129 Nef;Nef;Nef;Nef;Nef;Nef 75;83;122;134;192;205 78;86;125;137;195;208 31745412 HIV Drug Resistance among Patients Failing Therapy at a Tertiary Center in Oman: A Case Record Review. M184V/I, K103N/S, and G190A/S/E were the most common mutations detected among those patients. 2019 Oman medical journal Discussion HIV G190A;G190E;G190S;K103N;K103S;M184I;M184V 22;22;22;9;9;0;0 31;31;31;16;16;7;7 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. As previously described, M184V was the most prevalent NRTI mutation occurring in all the 10 major mutational patterns reported in this study. 2019 PloS one Discussion HIV M184V 25 30 NRTI 54 58 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. K103N also was the most prevalent NNRTI mutation and is responsible for cross-resistance in this drug class. 2019 PloS one Discussion HIV K103N 0 5 NNRTI 34 39 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. M184V is associated with high-level resistance to lamivudine and emtricitabine. 2019 PloS one Discussion HIV M184V 0 5 31751428 Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon. The second prevalent resistance-associated mutations were T215Y/F and Y181C in the NRTI and NNRTI respectively. 2019 PloS one Discussion HIV T215F;T215Y;Y181C 58;58;70 65;65;75 NNRTI;NRTI 92;83 97;87 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Along with T215S, we report on K101E, T215S + L210W and triple-class drug resistance pattern, as major contributors to the spread of resistant strains in Croatia. 2019 Scientific reports Discussion HIV K101E;L210W;T215S;T215S 31;46;11;38 36;51;16;43 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. For mutations M46I, T69D, G190E, K219Q and K219R reduced fitness compared to wild-type virus has been observed, as these tend to revert back to wild type. 2019 Scientific reports Discussion HIV G190E;K219Q;K219R;M46I;T69D 26;33;43;14;20 31;38;48;18;24 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. However, the high prevalence of the revertant T215S variants in the Croatian HIV-1 cohort is likely a hallmark of once highly prevalent therapy in Croatia. 2019 Scientific reports Discussion HIV T215S 46 51 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. In addition, PI resistance was determined in 10 (2.5%) persons, including 9 (2.2%) with triple-class drug resistance, mediated by the mutation pattern PI: V32I, I47V + NRTI: T215D/E + NNRTI: L100I, K103N. 2019 Scientific reports Discussion HIV I47V;K103N;L100I;T215D;T215E;V32I 161;198;191;174;174;155 165;203;196;181;181;159 NNRTI;NRTI;PI;PI 184;168;13;151 189;172;15;153 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. In contrast, the present study shows that the revertant T215S remains the most frequent SDRM, determined in 30 (7.4%) persons. 2019 Scientific reports Discussion HIV T215S 56 61 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. In four samples discordance was due to the SDRM T215S being detected by DS at low frequencies and falling below threshold in SS. 2019 Scientific reports Discussion HIV T215S 48 53 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. In respect to that, E138A was also found in our cohort, but was not reported in this study. 2019 Scientific reports Discussion HIV E138A 20 25 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. In the 2006-2008 analysis, phylogenetic inference identified eight distinct TCs and the largest TC consisted of MSM carrying T215S mutation. 2019 Scientific reports Discussion HIV T215S 125 130 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. In the previous study, high TDR was mainly due to one large TC of MSM with SDRM T215S, while NNRTI resistance-associated mutations were only present at a low frequency (2.4%) and PI resistance-associated mutations were not detected at all. 2019 Scientific reports Discussion HIV T215S 80 85 NNRTI;PI 93;179 98;181 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Most of the sequences with SDRMs (83.6%) formed local TCs, of which the T215S cluster of 53 persons remained the largest SDRM cluster in Croatia. 2019 Scientific reports Discussion HIV T215S 72 77 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. On the other hand, the largest TC with T215S is an expanding cluster that has contributed in the spread of HIV-1 infection in Croatia over the last two decades. 2019 Scientific reports Discussion HIV T215S 39 44 HIV infections 107 122 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Phylogenetic inference indicated a transmission link with one UK sequence with a similar mutation pattern, PI: V32I, M46L, I47A, V82A + NRTI: T215Y + NNRTI: L100I, K103N. 2019 Scientific reports Discussion HIV I47A;K103N;L100I;M46L;T215Y;V32I;V82A 123;164;157;117;142;111;129 127;169;162;121;147;115;133 NNRTI;NRTI;PI 150;136;107 155;140;109 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. reported TDR of 12.3% in a cohort of 750 HIV-infected persons diagnosed in northern Italy in the time period 2013-2016, with E138A mutation being the most frequent. 2019 Scientific reports Discussion HIV E138A 125 130 HIV infections 41 53 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. The TC with K101E, the triple-class resistance TC and the sub-cluster T215S + L210W were all identified as newly formed clusters. 2019 Scientific reports Discussion HIV K101E;L210W;T215S 12;78;70 17;83;75 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. These variants develop from strains containing T215Y/F mutations, primarily selected under the stavudine (d4T) and zidovudine (AZT) treatment and tend to persist for many years. 2019 Scientific reports Discussion HIV T215F;T215Y 47;47 54;54 31754119 Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. We found only one major InSTI mutation (G140A), three accessory resistance mutations (T97A, Q146QH, D232N) and a very high prevalence of polymorphism S230N (49/100, 49%), which is not associated with reduced InSTI susceptibility. 2019 Scientific reports Discussion HIV D232N;G140A;Q146H;Q146Q;S230N;T97A 100;40;92;92;150;86 105;45;98;98;155;90 INSTI;INSTI 24;208 29;213 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. A lower CD4 count at VF in the group with M184V/I further argues against this mutation being "protective" or "benign." These data are also consistent with reports of the pathogenic potential of M184V-containing viruses in both humans and animal models. 2020 The Journal of infectious diseases Discussion HIV M184I;M184V;M184V 42;42;194 49;49;199 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Because L74I was observed only in approximately 10% of those with M184V/I, we postulate that alternative mutations, less strongly linked to M184V/I or perhaps outside the region of the pol gene sequenced in this study, could have similar effects as L74I in participants with M184V/I. 2020 The Journal of infectious diseases Discussion HIV L74I;L74I;M184I;M184I;M184I;M184V;M184V;M184V 8;249;66;140;275;66;140;275 12;253;73;147;282;73;147;282 Pol 185 188 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Correlation with M184V/I has not been made to date, and in vitro experiments have not been performed with L74I + M184V/I-containing viruses. 2020 The Journal of infectious diseases Discussion HIV L74I;M184I;M184I;M184V;M184V 106;17;113;17;113 110;24;120;24;120 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Data from our study support the transmission potential of M184V/I-containing viruses in the context of prolonged VF and accumulated coevolved mutations in RT that occurs under "real-world" conditions. 2020 The Journal of infectious diseases Discussion HIV M184I;M184V 58;58 65;65 RT 155 157 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. In vitro experiments demonstrated that L74I restores replication efficiency to a virus with the M184V mutation over a single round of infection, and that enhancement was due to efficiency of HIV reverse transcription in viral particles. 2020 The Journal of infectious diseases Discussion HIV L74I;M184V 39;96 43;101 RT 195 216 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. L74I was first reported as a mutation associated with exposure to abacavir or less commonly tenofovir, and it appeared more common in patients with TAMs. 2020 The Journal of infectious diseases Discussion HIV L74I 0 4 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Our primary finding that VL was similar in participants with and without M184V/I at the time of VF was robust across baseline CD4 count, baseline VL, gender, and different NNRTI and NRTI drugs in the first-line treatment regimen. 2020 The Journal of infectious diseases Discussion HIV M184I;M184V 73;73 80;80 NNRTI;NRTI 172;182 177;186 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Our study was not designed to provide a mechanistic understanding of the relationship between M184 and fitness: it was designed to understand the pathogenic potential of M184V-containing viruses in patients treated in the real world. 2020 The Journal of infectious diseases Discussion HIV M184V 170 175 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. The emergence of L74I exclusively in patients with M184V/I suggests an in vivo selection advantage of L74I + M184V replication over M184V alone, at least in some individuals. 2020 The Journal of infectious diseases Discussion HIV L74I;L74I;M184I;M184V;M184V;M184V 17;102;51;51;109;132 21;106;58;58;114;137 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. Therefore, a complete understanding of 3TC efficacy is important, particularly given reports suggesting that 3TC use confers VL benefit despite high-level resistance to the drug in the form of the M184V/I. 2020 The Journal of infectious diseases Discussion HIV M184I;M184V 197;197 204;204 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We identified L74I as being specifically enriched in individuals with M184V and not present at all in those without M184V/I. 2020 The Journal of infectious diseases Discussion HIV L74I;M184I;M184V;M184V 14;116;70;116 18;123;75;123 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We observed lower baseline and VF CD4 counts in individuals with M184V/I, although rate of change of CD4 did not differ based on M184V/I status. 2020 The Journal of infectious diseases Discussion HIV M184I;M184I;M184V;M184V 65;129;65;129 72;136;72;136 31774913 Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I. We observed significant prevalence of L74I in subtypes C and CRF01_AE, although limited numbers of participants across subtypes hindered a full understanding of subtype distribution. 2020 The Journal of infectious diseases Discussion HIV L74I 38 42 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. E138Q is a nonpolymorphic accessory mutation, and in most studies, it caused low-level reductions in susceptibility to NVP, RPV, EFV and ETR. 2019 Current HIV research Discussion HIV E138Q 0 5 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. EFV and NVP, which are both NNRTIs, had the highest drug resistance rate in this study which was mainly caused by K103N, V179D, V106M and E138G/Q mutations. 2019 Current HIV research Discussion HIV E138G;E138Q;K103N;V106M;V179D 138;138;114;128;121 145;145;119;133;126 NNRTI 28 34 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. In addition, the study identified a rapidly growing drug resistance-related cluster from 2017 to 2018, which contains the V179D mutation or E138Q and V179D mutations. 2019 Current HIV research Discussion HIV E138Q;V179D;V179D 140;122;150 145;127;155 31778107 Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China. It was also found that the PDR rate did not significantly differ among the three main subtypes (CRF07_BC, CRF08_BC and CRF01_AE); however, in a previous study, HIV-1 CRF07_BC showed distinctive resistance evolution pathways in which the mutations K103N, Q197K, V179D and Y188L were the major resistance mutations. 2019 Current HIV research Discussion HIV K103N;Q197K;V179D;Y188L 247;254;261;271 252;259;266;276 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. 1g, h), suggesting that the mutations E560K and E560D conferred the virus to sufficiently utilize the CD4 receptor on the target cells with lower levels of CD4 receptors and may result in conformational changes to affect the binding of viral envelope protein gp120 to CD4 receptors indirectly. 2019 Retrovirology Discussion HIV E560D;E560K 48;38 53;43 Env;gp120 242;259 250;264 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. And as the analyzing above, E560D and E560G mutations reduced the stability of 6HB through rearrangements of hydrogen bonds between them and Q650 network (Additional file 1. 2019 Retrovirology Discussion HIV E560D;E560G 28;38 33;43 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. And E560K is observed in the screened HIV-1 JRcsf and LAI resistance strains to N36 and IZN36 in vitro. 2019 Retrovirology Discussion HIV E560K 4 9 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560D and E560G mutants showed less binding to HR2 but were still not resistant to T20 suggesting they are compensatory mutations with the major resistance mutations L544S and G547D. 2019 Retrovirology Discussion HIV E560G;G547D;L544S;E560D 10;176;166;0 15;181;171;5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560D mutation carries similar negative charge as wild type, but it has only shorter side chain than wild type and may interrupt the hydrogen bond with the longer distance (3.91 A) between E560D and Q650. 2019 Retrovirology Discussion HIV E560D;E560D 189;0 194;5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. E560K mutation still interacts with Q650 through hydrogen bond with shorter distance between them (2.37 A), or probably its two hydrogen atoms forms two hydrogen bonds with nitrogen atom of Q650. 2019 Retrovirology Discussion HIV E560K 0 5 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. In our previous work the mutations E560D and E560G were found in the resistance LAI strains under T20 selection in vitro by increasing its concentration gradually (our unpublished data). 2019 Retrovirology Discussion HIV E560D;E560G 35;45 40;50 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. In the present study the results showed that compared with wild-type pseudovirus, E560K mutant was resistant to N36 and IZN36 and was slightly sensitive to T20, E560D mutant showed similar IC50 values to N36 and IZN36 and was sensitive to T20, and E560G mutant was sensitive to all tested fusion peptide inhibitors (Table 1. 2019 Retrovirology Discussion HIV E560D;E560G;E560K 161;248;82 166;253;87 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Meanwhile, we also observed the lower Tm ( Tm: - 7 C) of 6HB containing G547D mutation compared to that containing wild type based on CD analysis (our unpublished data). 2019 Retrovirology Discussion HIV G547D 73 78 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. Mutation L544S removes the interactions between these hydrophobic residues and result in the destabilization of 6HB, possibly contributing to the resistance to T20 (Additional file 1. 2019 Retrovirology Discussion HIV L544S 9 14 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The 6HB containing E560G mutation is less stable than that containing wild type by 4 C and it can be explained by that the interaction between E560 and Q650 is interrupted. 2019 Retrovirology Discussion HIV E560G 19 24 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The higher Tm of 6HB containing E560K mutation from CD analysis may let virus form more stable endogenous bundle and be resistant to N peptide inhibitors, and it was also suspected to bind to T20 more stably. 2019 Retrovirology Discussion HIV E560K 32 37 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The increasing sensitivity to these bNAbs may be explained that the three mutants, especially E560D and E560K, promoted more exposure of neutralizing epitopes within MPER or extend exposure time of these epitopes indirectly. 2019 Retrovirology Discussion HIV E560D;E560K 94;104 99;109 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The mutant containing E560G substitution had lower infectivity in both U87CD4+CXCR4+ and RC4 cells than wild type. 2019 Retrovirology Discussion HIV E560G 22 27 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The present study showed that mutations at position 560 (E560K/D/G) conferred sensitivity to the bNAbs targeting MPER (Table 3. 2019 Retrovirology Discussion HIV E560D;E560G;E560K 57;57;57 66;66;66 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The pseudoviruses bearing Env containing E560K or E560D mutation showed higher infectivity in the RC4 cells than wild type (Additional file 1. 2019 Retrovirology Discussion HIV E560D;E560K 50;41 55;46 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The substitution of a positively charged residue Lysine (E560K), a negative charged residue Aspartic acid (E560D), or an uncharged residue Glycine (E560G) changed the size of side chain or charges and may disrupt the interactions between HR1 with HR2 or gp120. 2019 Retrovirology Discussion HIV E560D;E560G;E560K 107;148;57 112;153;62 gp120 254 259 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. The susceptibility analysis of the mutants harboring the separated mutations suggested that E560G mutation dramatically increased the resistance activity to T20 compared to the mutants with two mutations L544S and G547D (Table 2). 2019 Retrovirology Discussion HIV E560G;G547D;L544S 92;214;204 97;219;209 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. To gain insight into how the mutations affected the sensitivity of Env to peptide inhibitors and sCD4, we predicted atomic interactions in the adjacent regions of the E560K, E560G, and E560D mutations using PYMOL software. 2019 Retrovirology Discussion HIV E560D;E560G;E560K 185;174;167 190;179;172 Env 67 70 31796053 Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry. We found that resistance mutants containing L544S, G547D and E560G/D mutations in the selection of T20 in vitro (our unpublished paper). 2019 Retrovirology Discussion HIV E560D;E560G;G547D;L544S 61;61;51;44 68;68;56;49 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Here, sharing of specific DRMs at low within-host frequency (2%-19%), mainly RT D67N/G/E and P225H, between putative transmission pairs was observed relatively frequently (25 out of 66 clusters including persons sharing DRMs). 2020 The Journal of antimicrobial chemotherapy Discussion HIV D67E;D67G;D67N;P225H 80;80;80;93 88;88;88;98 RT 77 79 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Moreover, consistent with previous observations, DRMs with low transmission fitness due to high replicative impairment such as M184V/I and K65R were not shared within the Mexican network, and were observed mostly at low within-host frequencies in the study population. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184I;M184V 139;127;127 143;134;134 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Moreover, the higher odds of sharing K103N between younger persons and in smaller clusters also suggests important groups for intervention. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K103N 37 42 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Propagation of K103N within the network is noteworthy, and of high relevance not only to Mexico but also to many other resource-limited countries that still use efavirenz-based first-line ART regimens without availability of baseline HIV genotyping and weak viral load monitoring systems. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K103N 15 20 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Sharing of specific DRMs was common, especially K103N/S, revealing the potential for spread of pretreatment HIVDR. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K103N;K103S 48;48 55;55 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. The lack of fitness costs associated with this mutation in addition to the low-genetic barrier of efavirenz and its wide use as part of first-line ART regimens have resulted in worryingly high K103N prevalence in several countries. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K103N 193 198 31819984 Pretreatment HIV drug resistance spread within transmission clusters in Mexico City. Whether the decreasing trend of K103N sharing observed in the network is due to enrolment bias or to a real epidemiological effect remains to be explored. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K103N 32 37 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. Conversely, we observed a much lower frequency (4.3%) of M184 V/I resistance mutations among treatment-experienced patients than the provincial frequency of 30%, which may represent truly lower baseline rates or an underestimation due to M184 V/I's potential to be archived. 2019 BMC public health Discussion HIV M184I;M184I;M184V;M184V 57;238;57;238 65;246;65;246 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. In fact, among the seven newly diagnosed individuals with a K103 N/S mutation, three were women with living children, suggesting that prior exposure to nevirapine for MTCT may have been possible. 2019 BMC public health Discussion HIV K103N;K103S 60;60 68;68 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. Providers should initiate a first-line integrase-based cART regimen as soon as possible, recognizing that M184 V/I resistance mutations are rare (or possibly underestimated) and that NNRTIs should be avoided (as per current guidelines). 2019 BMC public health Discussion HIV M184I;M184V 106;106 114;114 IN;NNRTI 39;183 48;189 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. That said, the frequency of K103 N/S resistance mutations among treatment-experienced patients was identical to provincial data (17%). 2019 BMC public health Discussion HIV K103N;K103S 28;28 36;36 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. The frequency of both K103 N/S and M18 V/I resistance mutations was three-fold higher in our newly diagnosed population compared to provincial data. 2019 BMC public health Discussion HIV K103N;K103S;M18I;M18V 22;22;35;35 30;30;42;42 31842822 Delayed linkage to HIV care among asylum seekers in Quebec, Canada. The K103 N/S mutation predominated, reflecting that efavirenz and nevirapine continue to be widely used in many developing countries. 2019 BMC public health Discussion HIV K103N;K103S 4;4 12;12 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. 5a); however, the M184V mutation shifts the conformation equilibrium towards the catalytically ineffective state. 2019 Communications biology Discussion HIV M184V 18 23 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. A prior binary crystal structure of M184I RT-DNA predicted a steric clash with the oxathiolane ring. 2019 Communications biology Discussion HIV M184I 36 41 RT 42 44 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Additionally it was noted that there was movement of the primer terminus for which M184I or V is directly below. 2019 Communications biology Discussion HIV M184I 83 88 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Although M184V still conferred 30-fold selection against (+)-FTC-TP (Table 1), it seems likely that (+)-FTC may not choose for this mutation since the oxathiolane ring is turned away from M184. 2019 Communications biology Discussion HIV M184V 9 14 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Generally, M184I precedes the M184V mutation and can arise through a single nucleotide change from G to A. 2019 Communications biology Discussion HIV M184I;M184V 11;30 16;35 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. However, in both M184V-DNA (-)-FTC-TP and M184V-DNA dCTP the primer shifts back to a position comparable to WT. 2019 Communications biology Discussion HIV M184V;M184V 17;42 22;47 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. However, M184V requires a two nucleotide change and in some cases has been shown to mutate directly from WT and not through a progression of I to V. 2019 Communications biology Discussion HIV M184V 9 14 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. In addition, our crystal structures of HIV-1 RT M184V show how this mutation could potentially confer resistance to (-)-FTC-TP and (-)-3TC-TP. 2019 Communications biology Discussion HIV M184V 48 53 RT 45 47 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. In the binary structure of M184V-DNA, there is a shift in the DNA primer compared to RT-DNA. 2019 Communications biology Discussion HIV M184V 27 32 RT 85 87 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. In the case of (-)-FTC-TP and (-)-3TC-TP, M184V causes resistance by sterically hindering the oxathiolane ring and pushing the phosphates away from the primer strand DNA, thus locking them in a non-productive conformation. 2019 Communications biology Discussion HIV M184V 42 47 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. In the M184V binary structure reported here, the position of the primer terminus does not appear to have a large effect on the mechanism of resistance. 2019 Communications biology Discussion HIV M184V 7 12 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. It was reported that (+)-FTC selects for T215Y as opposed to M184V in cell culture. 2019 Communications biology Discussion HIV M184V;T215Y 61;41 66;46 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. M184V eventually outcompetes M184I based on higher RT polymerase activity and better processivity. 2019 Communications biology Discussion HIV M184I;M184V 29;0 34;5 Pol;RT 54;51 64;53 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. M184V is the primary resistance mutation generated during HIV treatment with FTC and 3TC. 2019 Communications biology Discussion HIV M184V 0 5 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. Taken together, our pre-steady-state kinetic data in combination with our crystal structures support the mechanism whereby the M184V mutation confers resistance via primarily affecting the binding and proper orientation of (-)-FTC-TP and (-)-3TC-TP within the active site of HIV-1 RT. 2019 Communications biology Discussion HIV M184V 127 132 RT 281 283 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The M184V mutant confers some of the highest resistance as a single mutation against an NRTI with up to >300-fold reduction in potency in enzyme-based assays and >500-fold reduction in cell-based assays for FTC and 3TC. 2019 Communications biology Discussion HIV M184V 4 9 NRTI 88 92 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. The net effect of the M184V mutation produces a steric hindrance by directly contacting the sulfur atom in the oxathiolane ring. 2019 Communications biology Discussion HIV M184V 22 27 31872074 Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance. This is consistent with measured Kd of nucleotide binding which increased from 0.10 and 0.25 microM with WT HIV-1 RT to 28 and 53 microM with M184V for (-)-FTC-TP and (-)-3TC-TP, respectively, and with measured substrate specificity (kp/Kd) which decreased from 1.0 and 0.27 microM-1 s-1 to 2.6 x 10-3 and 9.4 x 10-4 microM-1 s-1 for (-)-FTC-TP and (-)-3TC-TP, respectively (Table 1). 2019 Communications biology Discussion HIV M184V 142 147 RT 114 116 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. As expected, the consensus RT_A was enzymatically active, RT-An (K65R/M184 V) was compromised in the polymerase, and RT_Ann (K103N/G190S), in the RNase H activities. 2019 Oxidative medicine and cellular longevity Discussion HIV G190S;K103N;K65R 131;125;65 136;130;69 Pol;RT 101;58 111;60 31885806 HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist. We designed the consensus RT of HIV-1 clade A FSU_A strain (RT_A) and two RT_A variants with primary mutations of resistance to NRTI (K65R and M184V; RT_An) and NNRTI (K103N and G190S; RT_Ann). 2019 Oxidative medicine and cellular longevity Discussion HIV G190S;K103N;K65R;M184V 178;168;134;143 183;174;139;148 NNRTI;NRTI;RT 161;128;26 166;132;28 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Although natural polymorphism of M46I was reported in multiple HIV-1 subtypes (especially subtypes F and G) in ART-naive individuals, such high percentage of this mutation in CRF01_AE strains in Chinese ART-naive individuals was less likely a consequence of natural polymorphisms of the virus. 2020 EClinicalMedicine Discussion HIV M46I 33 37 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Although there was still a controversy on whether continued use of 3TC provides actual benefit, some studies demonstrated that maintaining 3TC treatment in the presence of the M184V mutation resulted in a greater risk for virologic failure, compared with switching to other NRTI drugs. 2020 EClinicalMedicine Discussion HIV M184V 176 181 NRTI 274 278 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Distinct from subtype B that had higher percentage of NRTI mutation M184V/I (26.3% vs. 2020 EClinicalMedicine Discussion HIV M184I;M184V 68;68 75;75 NRTI 54 58 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Furthermore, high percentage of PI mutation M46I/L (2.4%) was observed in CRF01_AE strains in ART-naive individuals, which was substantially higher than those (0.6-1.7%) observed in the surrounding countries (e.g. 2020 EClinicalMedicine Discussion HIV M46I;M46L 44;44 50;50 PI 32 34 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). K103N, Y181C/I and G190S/A) conferred high percentages (88-90%) of high- and intermediate-level resistance to EFV and NVP in ART-treated individuals across the country. 2020 EClinicalMedicine Discussion HIV G190A;G190S;Y181C;Y181I;K103N 19;19;7;7;0 26;26;14;14;5 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). M46I/L is a major mutation conferring resistance to PIs individually or together with other mutations. 2020 EClinicalMedicine Discussion HIV M46I;M46L 0;0 6;6 PI 52 55 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Similarly, another free NRTI drug AZT, which was often used in the first-line ART regimens, also faced an increased resistance by high percentage of mutation T215D/S/C among both ART-treated and ART-naive individuals. 2020 EClinicalMedicine Discussion HIV T215C;T215D;T215S 158;158;158 167;167;167 NRTI 24 28 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The finding that a few NRTI-associated (M184V/I) and NNRTI-associated (K103N/S, Y181C/I and G190A/S) SDRMs were responsible for most cases of acquired and transmitted drug resistance suggests that the current available first-line ART regimens containing to 3TC and/or EFV or NVP should be urgently amended, or promptly switched to the second-line regimens if individuals who are identified as carrying these mutations. 2020 EClinicalMedicine Discussion HIV G190A;G190S;K103N;K103S;M184I;M184V;Y181C;Y181I 92;92;71;71;40;40;80;80 99;99;78;78;47;47;87;87 NNRTI;NRTI 53;23 58;27 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The M184V/I mutation confers a high proportion of high- and intermediate-level resistance to 3TC, as well as FTC (self-paid NRTI drug), and has a high fitness cost for virus by reducing the replicative capacity of reverse transcriptase (RT). 2020 EClinicalMedicine Discussion HIV M184I;M184V 4;4 11;11 RT;NRTI;RT 214;124;237 235;128;239 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). The observation of a high percentage of M184V/I in ART-treated and ART-naive individuals across the country suggests revision in the treatment regimens. 2020 EClinicalMedicine Discussion HIV M184I;M184V 40;40 47;47 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Third, two NRTI (M184V/I and K65R), three NNRTI (K103N/S, Y181C/I and G190A/S) and one PI (M46I/L) mutations had higher prevalence than other SDRMs in China. 2020 EClinicalMedicine Discussion HIV G190A;G190S;K103N;K103S;K65R;M184I;M184V;M46I;M46L;Y181C;Y181I 70;70;49;49;29;17;17;91;91;58;58 77;77;56;56;33;25;25;97;97;65;65 NNRTI;NRTI;PI 42;11;87 47;15;89 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). This hypothesis was supported by the phylogenetic analysis that showed that most M46I/L-carrying CRF01_AE strains formed genetic clusters. 2020 EClinicalMedicine Discussion HIV M46I;M46L 81;81 87;87 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). Treatment interruptions are almost invariably associated with a rebound of plasma HIV-1 RNA levels and facilitate the emergence of drug resistance mutations (especially for M184V). 2020 EClinicalMedicine Discussion HIV M184V 173 178 31922125 Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). With respect to high prevalence of M184V/I in subtype B in ART-naive individuals, the reasons are possibly related to acquisition of this mutation from patients failing treatment with resistant strains, prior exposures to ART, or undisclosed ART. 2020 EClinicalMedicine Discussion HIV M184I;M184V 35;35 42;42 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Although not proven, a reduction in the incidence of new DRMs would be consistent with increased HIV replication fidelity 13 linked to maintenance of the M184V mutation; we confirmed that the M184V/I mutation could be detected in a majority of the available follow-up sequences among patients on 3TC/FTC, but was absent in > 80% of follow-up sequences > 6 months from switch for those people not on 3TC/FTC. 2020 HIV medicine Discussion HIV M184I;M184V;M184V 192;154;192 199;159;199 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Earlier tissue culture studies found that the M184V/I mutation delayed emergence of resistance to the NNRTI efavirenz and to the PI amprenavir 14, although no such effect was found for nevirapine 14, 40 or ritonavir 41. 2020 HIV medicine Discussion HIV M184I;M184V 46;46 53;53 NNRTI;PI 102;129 107;131 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. In our analysis of viral suppression following detection of M184V/I, we found that the most important factor in predicting success, other than baseline VL, was full susceptibility to at least one drug in the new regimen. 2020 HIV medicine Discussion HIV M184I;M184V 60;60 67;67 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. In the ODIN trial of darunavir-based ART, the presence of the M184V/I mutation at baseline was predictive of successful viral suppression 36. 2020 HIV medicine Discussion HIV M184I;M184V 62;62 69;69 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. It is therefore possible that maintenance of M184V/I is beneficial in this regard for some ART regimens but not others. 2020 HIV medicine Discussion HIV M184I;M184V 45;45 52;52 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. One in vitro study found that the presence of the M184V/I mutation prevented the appearance of DRMs for HIV-infected tissue cultures exposed to dolutegravir, but not for those exposed to raltegravir or elvitegravir 15. 2020 HIV medicine Discussion HIV M184I;M184V 50;50 57;57 HIV infections 104 116 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Recent interest in the continued use of 3TC or FTC in the presence of the M184V/I mutation has focused on the topic of dual-therapy regimens. 2020 HIV medicine Discussion HIV M184I;M184V 74;74 81;81 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The high level of use of regimens containing FTC following the detection of M184V/I since 2007 can be attributed to the availability and widespread use of co-formulated tablets with TDF [i.e. 2020 HIV medicine Discussion HIV M184I;M184V 76;76 83;83 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The potential vulnerability of these regimens to compromise by the M184V/I mutation is a source of concern, as bPI 31 or dolutegravir 32 monotherapy is known to be suboptimal, although there is some evidence that bPI + 3TC dual maintenance therapy is effective in PLHIV with the previous detection of M184V 8, 33. 2020 HIV medicine Discussion HIV M184I;M184V;M184V 67;67;301 74;74;306 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. The use of 3TC or FTC was continued in 43.2% of PLHIV overall at ART switch following the detection of the M184V/I mutation, and from 2007 onwards one of these drugs was continued in the majority of people. 2020 HIV medicine Discussion HIV M184I;M184V 107;107 114;114 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Very few people in our data set were switched to monotherapy or dual therapy including 3TC or FTC following the detection of M184V/I, and so we were not able to evaluate 3TC/FTC use in this setting. 2020 HIV medicine Discussion HIV M184I;M184V 125;125 132;132 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. We did not find evidence of a benefit of 3TC or FTC use following the detection of the M184V/I mutation in terms of viral suppression in our retrospective analysis of routine clinical data. 2020 HIV medicine Discussion HIV M184I;M184V 87;87 94;94 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. We did not find that continued 3TC or FTC use was associated with reduced risk of first detection of new DRMs following ART switch in PLHIV with M184V/I, but we did find some evidence for a reduced incidence rate of new DRMs over the entire follow-up period. 2020 HIV medicine Discussion HIV M184I;M184V 145;145 152;152 31927793 Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation. Where randomized or other high-quality evidence exists for specific ART regimens, this should be used to guide judgements regarding the use of 3TC or FTC in PLHIV with the M184V/I mutation present. 2020 HIV medicine Discussion HIV M184I;M184V 172;172 179;179 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 1B), the Q4R substitution significantly enhanced the CPSF6-358 resistance of the WT virus. 2020 AIDS research and human retroviruses Discussion HIV Q4R 9 12 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. 4C) yielded a phenotype similar to that seen with the Q4R/Q112D substitutions. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 58;54 63;57 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Although the mechanism whereby the Q4R mutation modulates infectivity of the WT and RGDA/Q112D viruses remains unknown, we suggest that the mutation may alter the stability of the viral core. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 89;35 94;38 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Considering the pivotal roles of CPSF6-CA interaction for nuclear entry pathway and integration targeting, along with the fact that CPSF6 binding is strictly conserved among primate lentiviruses, we speculate that the Q4R substitution arose in the SIVcpzMT145 strain to compensate for the decreased CA-CPSF6 interaction due to the Q112E substitution (or vice versa). 2020 AIDS research and human retroviruses Discussion HIV Q112E;Q4R 331;218 336;221 Capsid;Capsid 39;299 41;301 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. However, the Q4R virus produced luciferase values sufficient to permit evaluation of the infectivity in both CPSF6-358-expressing and control cells. 2020 AIDS research and human retroviruses Discussion HIV Q4R 13 16 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In contrast, addition of the Q4R mutation to the RGDA/Q112D background enhanced infectivity. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 54;29 59;32 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In future studies, it will be interesting to investigate whether Q4R, Q112D, and Q4R/Q112D viruses also induce such a phenomenon. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q112D;Q4R;Q4R 70;85;65;81 75;90;68;84 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In support of this model, we were able to demonstrate that viruses harboring either the Q4R substitution or the Q112D substitution showed increased CPSF6-358 resistance. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 112;88 117;91 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In the context of the lower infectivity of the Q4R viruses, there may be concerns about the results of our infection assay in CPSF6-358-expressing cells. 2020 AIDS research and human retroviruses Discussion HIV Q4R 47 50 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. In this study, we investigated the possibility that the Q4R substitution might be specifically selected by the RGDA/Q112D virus to restore the CA-CPSF6 interaction. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 116;56 121;59 Capsid 143 145 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Interestingly, the Q4R, Q112D, or Q112E substitutions are regularly found in the CA proteins of SIV strains, including SIVdeb, SIVmus, SIVmac, and SIVsm. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q112E;Q4R 24;34;19 29;39;22 Capsid 81 83 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. It should be noted that the effect of Q4R or Q112D substitutions on CA-CPSF6 interactions was observed both in the presence. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 45;38 50;41 Capsid 68 70 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Nevertheless, the use (in future studies) of a biochemical assay to directly test binding between CPSF6 and CA would significantly improve our understanding of the characteristic properties of the Q4R mutation. 2020 AIDS research and human retroviruses Discussion HIV Q4R 197 200 Capsid 108 110 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Our recent study demonstrated that sequences encoding the Q4R-substituted CA were selected during adaptation of the RGDA/Q112D virus in IFN-beta-treated cells. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 121;58 126;61 Capsid 74 76 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Our structural models proposed the possibility of a salt bridge interaction between residue 4 and residue 112 of the CA mutants harboring both the Q4R and Q112D substitutions. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 155;147 160;150 Capsid 117 119 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Specifically, while the Q4R substitution decreased CPSF6-358 resistance of the RGDA/Q112D strain. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 84;24 89;27 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. The combination of these substitutions (Q4R/Q112D substitutions) restored CPSF6-358 resistance to a level comparable to that of the WT virus. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 44;40 49;43 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. Therefore, it is reasonable to speculate that the Q4R mutation is favored on the RGDA/Q112D backbone but not on the WT backbone. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 86;50 91;53 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. These findings suggest that the combination of Q4R and Q112D/Q112E substitutions might be under positive selection in the HIV-1-lineage viruses to maintain the CA-CPSF6 interaction. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q112E;Q4R 55;61;47 60;66;50 Capsid 160 162 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We also demonstrated that the combination of Q4R and Q112E substitutions. 2020 AIDS research and human retroviruses Discussion HIV Q112E;Q4R 53;45 58;48 31941344 The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-1. We first demonstrated that Q4R substitution had opposing impacts on the CA-CPSF6 interaction when comparing between the RGDA/Q112D and WT viruses. 2020 AIDS research and human retroviruses Discussion HIV Q112D;Q4R 125;27 130;30 Capsid 72 74 31943114 Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase. Alignment of this region among phylogenetically diverse RTs also shows a high level of conservation with variations found only at three positions (N418S, V423I and K424R), and even then only for MVP5180 and EHO, the two RTs that are most distant from group M subtype B (HXB2) in the panel (Supplementary Figure S10). 2020 Nucleic acids research Discussion HIV K424R;N418S;V423I 164;147;154 169;152;159 RT;RT 56;220 59;223 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. A notable observation in our study is that participants with only the K103N mutation, the most prevalent DRM conferring high-level of resistance to NNRTI, had similar rates of virologic failure compared to those with wild-type genotypes when prescribed EFV+3TC+TDF, but increased rates of virologic failure with NVP-based ART. 2020 EClinicalMedicine Discussion HIV K103N 70 75 NNRTI 148 153 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. A South African study recently reported that PDR primarily with the single K103N mutation was not associated with increased rates of virologic failure during ART with TDF+FTC+EFV. 2020 EClinicalMedicine Discussion HIV K103N 75 80 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. An economical and easy to use point of care OLA kit that assesses NNRTI mutations K103N, Y181C, G190A and NRTI mutations M184V and K65R could be used in resource-limited settings to test patients prior to starting EFV-based ART, at virologic failure to guide the choice of 2nd-line ART, or before switching to dolutegravir-based ART. 2020 EClinicalMedicine Discussion HIV G190A;K103N;K65R;M184V;Y181C 96;82;131;121;89 101;87;135;126;94 NNRTI;NRTI 66;106 71;110 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Compared to Sanger sequencing, the OLA used in this study identified PDR in all but one participant (with K70R) who subsequently experienced virologic failure. 2020 EClinicalMedicine Discussion HIV K70R 106 110 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. In our study, participants with single K103N and virologic suppression (mostly taking EFV-based ART) had a median mutant load of 11,790 copies/mL, significantly higher than previously described thresholds for virologic failure. 2020 EClinicalMedicine Discussion HIV K103N 39 44 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Other studies using next generation sequencing found that G190A, or other NNRTI mutations were more prevalent than K103N or Y181C. 2020 EClinicalMedicine Discussion HIV G190A;K103N;Y181C 58;115;124 63;120;129 NNRTI 74 79 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. PDR with NRTI mutations K65R and M184V were detected infrequently and, except for one participant with a single M184V, always in combination with NNRTI mutations. 2020 EClinicalMedicine Discussion HIV K65R;M184V;M184V 24;33;112 28;38;117 NNRTI;NRTI 146;9 151;13 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Single Y181C and G190A mutations appeared to increase virologic failure with NVP-ART more than EFV-ART, but the prevalence of these mutations was insufficient for statistical comparison. 2020 EClinicalMedicine Discussion HIV G190A;Y181C 17;7 22;12 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Some of the aforementioned studies used allele-specific-PCR to detect K103N alone, or K103N +Y181C. 2020 EClinicalMedicine Discussion HIV K103N;K103N;Y181C 70;86;93 75;91;98 31956856 Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya. Using allele-specific-PCR, K103N at levels of >2000 copies/mL were associated with virologic failure of EFV-ART, others described a dose-dependent risk of virologic failure starting at 10-99 copies/mL, and a study using next-generation-sequencing suggested drug-resistant variants at <1000 copies/mL were not associated with virologic failure of 1st-line NNRTI-ART. 2020 EClinicalMedicine Discussion HIV K103N 27 32 NNRTI 355 360 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. For NNRTI class, K103N mutation (53.8%) was indicated as the most prevalent mutation followed by G190A/S/E/G (30.2%) similar to a study done in sub-Saharan Africa that indicated K103N (38.7%) and G190A/S/E/G (21.8%) as the most prevalent. 2020 AIDS research and therapy Discussion HIV G190A;G190A;G190E;G190E;G190G;G190G;G190S;G190S;K103N;K103N 97;196;97;196;97;196;97;196;17;178 108;207;108;207;108;207;108;207;22;183 NNRTI 4 9 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. However, M184V/I (67 (55.8%), p = 0.015), Y188L (9 (100%), p = 0.008) and TAMs (44 (51.8%), p = 0.011) were noted more in subtype A, but the number of occurrence of these mutations could not affect the overall association, therefore the study finds these individual mutation observations statistically irrelevant. 2020 AIDS research and therapy Discussion HIV M184I;M184V;Y188L 9;9;42 16;16;47 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. K65R is highly selected for in TDF containing regimens. 2020 AIDS research and therapy Discussion HIV K65R 0 4 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. On the other hand, mutation L210W (75%, p = 0.03) and T215 mutations (70%, p = 0.0005) designated as TAMs were significantly more in the AZT/3TC/EFV. 2020 AIDS research and therapy Discussion HIV L210W 28 33 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. TAMs and K65R had a prevalence of 35.7% and 23.1% respectively, similar to a study done in Uganda where K65R mutation had a prevalence of 25%. 2020 AIDS research and therapy Discussion HIV K65R;K65R 9;104 13;108 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. The high prevalence of K65R might be attributed to the fact that many people had been on a TDF containing regimen for prolonged times and they were beginning to fail. 2020 AIDS research and therapy Discussion HIV K65R 23 27 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. The high prevalence of M184V might be attributed to the continued usage of lamivudine as a backbone in all regimens in Uganda and all over sub-Saharan since the presence of this mutation reduces the viral replicative fitness and increases susceptibility to TDF and AZT. 2020 AIDS research and therapy Discussion HIV M184V 23 28 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. The study further noted that within the NRTI class, M184V/I mutations had the highest prevalence of 65.9% similar to a study done in Uganda where M184V was noted with the highest prevalence of 81.2%. 2020 AIDS research and therapy Discussion HIV M184I;M184V;M184V 52;52;146 59;59;151 NRTI 40 44 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. This is anticipated given the fact that mutation K65R is highly selected for in TDF containing regimens and mutation L74V appears to be associated with poor treatment outcomes in TDF-based regimens. 2020 AIDS research and therapy Discussion HIV K65R;L74V 49;117 53;121 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. This was anticipated given the fact that Efavirenz is highly used as the preferred NNRTI in this region and mutations K103N, G190A are among the most common single mutations that confer high-level resistance to all the first-generation NNRTIs. 2020 AIDS research and therapy Discussion HIV G190A;K103N 125;118 130;123 NNRTI;NNRTI 83;236 88;242 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. Within the NNRTI class, G190 mutations (38 (69.1%), p = 0.015), Y181C/I/Y (22 (78.6%), p = 0.008) and L1001 (14 (82.4%), p = 0.019) mutations were significantly noted more in TDF/3TC/EFV whereas K238T (10 (71.4%), p = 0.034) noted more in AZT/3TC/EFV regimen. 2020 AIDS research and therapy Discussion HIV K238T;Y181C;Y181I;Y181Y 195;64;64;64 200;73;73;73 NNRTI 11 16 32005262 Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. Within the NRTI class, individual mutations differed between these two regimens where mutations K65R (95.2%, p = 0.00005), Y115F (85.0%, p = 0.004) and L74V/I (82.6%, p = 0.004) appeared more frequently in the TDF/3TC/EFV. 2020 AIDS research and therapy Discussion HIV K65R;L74I;L74V;Y115F 96;152;152;123 100;158;158;128 NRTI 11 15 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Because the samples from G1015R between week 27 and week 214 were not available for analysis, we could not precisely determine when these mutations were selected between those two time points. 2020 Viruses Discussion HIV G1015R 25 31 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Escape mutations were identified in V2, loop D and V5 regions by analyzing of SGA sequences from longitudinal plasma samples in G1015R. 2020 Viruses Discussion HIV G1015R 128 134 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. HIV-1 25710 was similarly neutralized by plasma from G1015R and G1020R. 2020 Viruses Discussion HIV G1015R;G1020R 53;64 59;70 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. One other interesting observation is that the N279A and N280D mutations rendered viruses more sensitive to neutralization by plasma. 2020 Viruses Discussion HIV N279A;N280D 46;56 51;61 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. Resistance of HIV-1 mutants with known bnAb escape mutations to neutralization by plasma was only detected after many years of infection in both macaques (G1015R and G1020R). 2020 Viruses Discussion HIV G1015R;G1020R 155;166 162;172 32023860 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques. This is also in agreement with the results from a study in which the N279D mutation could increase Ab affinity maturation by decreasing the dependence of Abs on this amino acid and likely played a role in the development of neutralization breadth to the CD4 binding sites. 2020 Viruses Discussion HIV N279D 69 74 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. According to our findings, the frequency of the substitution Q148+ >=1 secondary mutation(s) (G140A/C/S, L74I or E138A/K/T) was 12%. 2020 AIDS research and therapy Discussion HIV E138A;E138K;E138T;G140A;G140C;G140S;L74I 113;113;113;94;94;94;105 122;122;122;103;103;103;109 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. Also, we found the L101I/T124A combination at a higher frequency in our cohort (28%) than that reported by Saladini et al. 2020 AIDS research and therapy Discussion HIV L101I;T124A 19;25 24;30 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. More information is needed to further recommend the use of DTG in naive patients harbouring the E157Q substitution as suggested by Charpentier and Descamps. 2020 AIDS research and therapy Discussion HIV E157Q 96 101 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. On the other hand, we do not find a significant difference between the mean viral load of the subjects with DTG resistance compared to the subjects without DTG resistance (n = 22), nor with samples harbouring a G140S/A + Q148H/R/K combination (n = 3) as described in that study. 2020 AIDS research and therapy Discussion HIV G140A;G140S;Q148H;Q148K;Q148R 211;211;221;221;221 218;218;230;230;230 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. The E157Q substitution (found in subject 13) is a natural polymorphism described as a compensatory mutation for R263K-mediated DTG resistance and after RAL exposure. 2020 AIDS research and therapy Discussion HIV E157Q;R263K 4;112 9;117 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. The L101I/T124A which may vary between HIV subtypes as reported by Garrido et al. 2020 AIDS research and therapy Discussion HIV L101I;T124A 4;10 9;15 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. The presence of the N155H substitution (one of the second most frequent in our study) reduces both RAL and EVG susceptibility but does not, alone, compromise DTG nor BIC by itself (thus, having more resistance to RAL leads to more EVG cross-resistance). 2020 AIDS research and therapy Discussion HIV N155H 20 25 32041622 HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study. This is important since the presence of the G140S mutation in combination with the Q148H mutation has been described to improve the viral fitness and increase the viral load in RAL-resistant subjects. 2020 AIDS research and therapy Discussion HIV G140S;Q148H 44;83 49;88 32045455 HIV-1 subtypes and drug resistance mutations among female sex workers varied in different cities and regions of the Democratic Republic of Congo. Moreover, we also observed the K65R mutation, which can compromise the efficacy of d4T in first-line regimens and ABC and ddI in second-line regimens in the DRC. 2020 PloS one Discussion HIV K65R 31 35 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Although S68G did not directly alter the drug susceptibility of the virus, it compensated for the loss of replication fitness associated with the K65R mutation in CRF01_AE HIV-1. 2020 BMC infectious diseases Discussion HIV K65R;S68G 146;9 150;13 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Based on the available evidence, it is suggested that S68G may be new mutation associated with the development of drug resistance. 2020 BMC infectious diseases Discussion HIV S68G 54 58 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. found that five patients with the wild-type virus at baseline developed K65R at the time of failure, and four of those patients also acquired the S68G mutation. 2020 BMC infectious diseases Discussion HIV K65R;S68G 72;146 76;150 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. found that the S68G mutant was the dominant quasispecies, whereas K65R/S68G double mutant was the minor quasispecies. 2020 BMC infectious diseases Discussion HIV K65R;S68G;S68G 66;15;71 70;19;75 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Given the importance of K65 residues in the RT function of HIV-1, and the observed reduced fitness of the K65R mutant, the virus must evolve compensatory mutations against the impairment. 2020 BMC infectious diseases Discussion HIV K65R 106 110 RT 44 46 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Hence, the K65R mutation may be induced first as the major mutation under the pressure of ART, while S68G may be an accessory mutation of K65R that is subsequently caused on the basis of the K65R mutation. 2020 BMC infectious diseases Discussion HIV K65R;K65R;K65R;S68G 11;138;191;101 15;142;195;105 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. However, the pre-existence of the S68G natural polymorphism may not accelerate the occurrence of the K65R mutation. 2020 BMC infectious diseases Discussion HIV K65R;S68G 101;34 105;38 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. However, the S68G mutation helps to compensate the loss of replicative fitness, which is similar to that of subtype B. 2020 BMC infectious diseases Discussion HIV S68G 13 17 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. However, the unexpected high frequency of the S68G mutation in combination with the K65R mutation in the CRF01_AE strain has not been previously reported. 2020 BMC infectious diseases Discussion HIV K65R;S68G 84;46 88;50 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In this study, we focused on the phenotype of S68G in the CRF01_AE virus. 2020 BMC infectious diseases Discussion HIV S68G 46 50 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In this study, we found that the S68G mutation was a common natural polymorphism in various subtypes of HIV-1, predominantly among CRF01_AE strains. 2020 BMC infectious diseases Discussion HIV S68G 33 37 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. In this study, we performed next-generation sequencing to explore the evolutionary relationship between K65R and S68G mutations using longitudinal samples. 2020 BMC infectious diseases Discussion HIV K65R;S68G 104;113 108;117 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. It has also been speculated that the K65R substitution improves the fidelity of the polymerase, thereby reducing the occurrence of several types of RT errors, including substitution and frameshift mutations. 2020 BMC infectious diseases Discussion HIV K65R 37 41 Pol;RT 84;148 94;150 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Moreover, a time lag was detected between the occurrence of the S68G and K65R mutations. 2020 BMC infectious diseases Discussion HIV K65R;S68G 73;64 77;68 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Moreover, previous studies showed that patients infected with subtype B and non-B subtype HIV-1, who failed ART and developed the K65R mutation, also acquired the S68G mutation. 2020 BMC infectious diseases Discussion HIV K65R;S68G 130;163 134;167 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Our results demonstrated that the frequency of the K65R/S68G double mutation was lower than that of the K65R mutation in vivo. 2020 BMC infectious diseases Discussion HIV K65R;K65R;S68G 51;104;56 55;108;60 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Owing to the high success rate of antiviral therapy in our cohort, only four patients with K65R/S68G double mutations were analyzed. 2020 BMC infectious diseases Discussion HIV K65R;S68G 91;96 95;100 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. reported that mutations at position 68 followed the initial selection for K65R and M184 V mutations. 2020 BMC infectious diseases Discussion HIV K65R;M184V 74;83 78;89 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Several studies have examined the evolution of the K65R and S68G mutations using standard testing for HIV drug resistance or molecular clones. 2020 BMC infectious diseases Discussion HIV K65R;S68G 51;60 55;64 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Studies investigating a greater number of cases are warranted to elucidate the functional role of the S68G mutation. 2020 BMC infectious diseases Discussion HIV S68G 102 106 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. Svarovskaia evaluated the role of the S68G in combination with K65R in subtype B. 2020 BMC infectious diseases Discussion HIV K65R;S68G 63;38 67;42 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The analysis revealed that S68G mutations partially restored the replication defect associated with the K65R mutation; however, it did not cause significant change in resistance of HIV-1 to NRTIs. 2020 BMC infectious diseases Discussion HIV K65R;S68G 104;27 108;31 NRTI 190 195 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. The S68G mutation often occurred following the K65R mutation in patients infected with CRF01_AE who failed treatment. 2020 BMC infectious diseases Discussion HIV K65R;S68G 47;4 51;8 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. This finding suggested that the S68G mutation may not be linked to the K65R mutation. 2020 BMC infectious diseases Discussion HIV K65R;S68G 71;32 75;36 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. This timing was later than that observed for the remaining three patients not carrying the S68G polymorphism prior to treatment, suggesting that the S68G mutation may not accelerate the development of the K65R mutation. 2020 BMC infectious diseases Discussion HIV K65R;S68G;S68G 205;91;149 209;95;153 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. We disclosed the minor role of the K65R mutation with and without S68G in susceptibility to NRTI. 2020 BMC infectious diseases Discussion HIV K65R;S68G 35;66 39;70 NRTI 92 96 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. We found that the mutation rate of S68G increased in almost all HIV-1 subtypes in drug-experienced populations, with the greatest increase noted among CRF01_AE strains. 2020 BMC infectious diseases Discussion HIV S68G 35 39 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. We noticed that, in one patient with > 90% quasispecies carrying the S68G mutation prior to treatment, the K65R mutation was not detected until 7 months post ART. 2020 BMC infectious diseases Discussion HIV K65R;S68G 107;69 111;73 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. We sought to investigate whether the preexistence of the S68G natural polymorphism prior to treatment could assist the development of the K65R mutation. 2020 BMC infectious diseases Discussion HIV K65R;S68G 138;57 142;61 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. We subsequently examined the phenotype of S68G. 2020 BMC infectious diseases Discussion HIV S68G 42 46 32046664 The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains. With regard to patients who developed the K65R/S68G double mutation, restoration of the replication fitness of the virus through a compensatory mutation can help the virus survive under drug pressure, potentially leading to disease progression. 2020 BMC infectious diseases Discussion HIV K65R;S68G 42;47 46;51 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Due to the decrease in susceptibility, patients infected with HIV-1 with the M184 V mutation continue treatment with Lamivudine, resulting in continuous exposure, and consequently, higher frequency of the mutation. 2020 Medicine Discussion HIV M184V 77 83 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. K103N and V106A individually can reduce susceptibility of HIV-1 to Nevirapine and Efavirenz by as much as 50-fold, and together with other mutations found in this study, high-level resistance can be acquired. 2020 Medicine Discussion HIV V106A;K103N 10;0 15;5 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. M184 V also increases susceptibility to Zidovudine, Stavudine, and Tenofovir, and is associated with a clinically significant reduction in HIV-1 replication in vivo. 2020 Medicine Discussion HIV M184V 0 6 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. NNRTI associated mutations detected included V90I, K103N, Y181C, H221Y, K101H, G190A, V106A, F227L, and K238T. 2020 Medicine Discussion HIV F227L;G190A;H221Y;K101H;K103N;K238T;V106A;V90I;Y181C 93;79;65;72;51;104;86;45;58 98;84;70;77;56;109;91;49;63 NNRTI 0 5 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Other mutations detected in this study, which have been shown to confer resistance to NRTIs, were M184I, T69N, L74I, M41L, K70R/E, T215Y/F, and K219E. 2020 Medicine Discussion HIV K219E;K70E;K70R;L74I;M184I;M41L;T215F;T215Y;T69N 144;123;123;111;98;117;131;131;105 149;129;129;115;103;121;138;138;109 NRTI 86 91 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Supplementary Digital Content 3) has been shown previously.M184 V mutation causes high-level resistance to Lamivudine, and therefore the high frequency of the mutation observed in this study is not unusual since the drug is the most common NRTI in use in Ghana. 2020 Medicine Discussion HIV M184V 59 65 NRTI 240 244 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. T215Y/F and K219E are major TAMs which give rise to high-level resistance to Zidovudine and Stavudine, especially when the mutations occur in concert with accessory TAMs like M41L, D67N, and K70R. 2020 Medicine Discussion HIV D67N;K219E;K70R;M41L;T215F;T215Y 181;12;191;175;0;0 185;17;195;179;7;7 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. The predominance of M184 V and D67N among mutations associated with resistance to NRTIs in subtype G and CRF02_AG observed in this study. 2020 Medicine Discussion HIV D67N;M184V 31;20 35;26 NRTI 82 87 32049783 High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. The presence of the L74I mutation in combination with the M184 V causes high-level resistance to both Abacavir and Didanosine. 2020 Medicine Discussion HIV L74I;M184V 20;58 24;64 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. A study on a London cohort in the United Kingdom found that different baseline polymorphisms, including V90I, A98S, and K103R, were associated with virologic failure, but their effects could not be differentiated from the impacts of the different treatment regimens and HIV strains. 2020 BMC infectious diseases Discussion HIV A98S;K103R;V90I 110;120;104 114;125;108 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Among these DRMs, L228R occurred simultaneously or following the appearance of Y181C, and it might be an accessory mutation to Y181C. 2020 BMC infectious diseases Discussion HIV L228R;Y181C;Y181C 18;79;127 23;84;132 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. In this study, for the first time, it was suggested that L228R might be associated with the known DRM Y181C and it might act as an accessory mutation to Y181C based on a co-variation analysis and longitudinal evolution study. 2020 BMC infectious diseases Discussion HIV L228R;Y181C;Y181C 57;102;153 62;107;158 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. In this study, the polymorphisms at five known drug resistance-associated sites (V179I/D, V118I, K103R, K238R, and E40Q) were polymorphic accessory mutations or other mutations that did not independently decrease drug sensitivity. 2020 BMC infectious diseases Discussion HIV E40Q;K103R;K238R;V118I;V179D;V179I 115;97;104;90;81;81 119;102;109;95;88;88 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. More importantly, we detected two mutations with significant increases but without annotation in the Stanford HIVdb algorithm, V75 L and L228R. 2020 BMC infectious diseases Discussion HIV L228R;V75L 137;127 142;132 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Only V75 L, a low-frequency mutation, was associated with virologic failure, implying that most polymorphisms in CRF01_AE seldom lead to TF. 2020 BMC infectious diseases Discussion HIV V75L 5 10 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Second, the impact of the L228R mutation with or without Y181C needs further validation using virus growth competition and drug resistance phenotype assays. 2020 BMC infectious diseases Discussion HIV L228R;Y181C 26;57 31;62 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. Site 75 is a drug resistance-associated site but no explanation for V75 L is provided in the Stanford HIVdb algorithm. 2020 BMC infectious diseases Discussion HIV V75L 68 73 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The L228R mutation has been reported to be related to the treatment of non-B HIV-1 subtypes in several studies, but its phenotype has not yet been described. 2020 BMC infectious diseases Discussion HIV L228R 4 9 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The most common acquired DRMs among CRF01_AE were K65R, M184 V, G190S/C, Y181C, and K103R, all of which are also common among subtype B and other subtypes. 2020 BMC infectious diseases Discussion HIV G190C;G190S;K103R;K65R;M184V;Y181C 64;64;84;50;56;73 71;71;89;54;62;78 32102660 Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. The V75 L mutation has been reported to provide a selective advantage by allowing escape from the host immune responses and it is believed to be a TDF-associated mutation. 2020 BMC infectious diseases Discussion HIV V75L 4 9 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. A limitation of this study was that our patient group were mainly ART-experienced and as such there may be a different prevalence of L74I in treatment-naive individuals. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I 133 137 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Furthermore, although L74I was associated with VF in two studies including the long-acting injectable cabotegravir, it is not known whether L74I contributed to VF or what the impact on dolutegravir might be. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I;L74I 22;140 26;144 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. In most cases there was no change in variant frequencies, consistent with L74I being transmitted between individuals following a founder effect and L74I reverting rarely, even during second-line ART failure. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I;L74I 74;148 78;152 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. In vitro studies are needed to determine whether L74I facilitates high-level INSTI resistance in non-B subtypes and clinical studies are necessary to determine whether L74I at baseline impacts clinical or virological outcomes on integrase inhibitors, even when short-term outcomes in cross-sectional studies appear favourable. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I;L74I;L74I;L74I 50;169;49;168 54;173;53;172 IN;INSTI 229;77 238;82 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. One individual out of 115 had both L74I and the signature dolutegravir mutation R263K detected by next-generation sequencing, though R263K was a minority variant. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I;R263K;R263K 35;80;133 39;85;138 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Recently, a series of VF patients in a trial of the integrase inhibitor cabotegravir were found to harbour L74I (a polymorphic mutation that is weakly selected for by INSTI therapy) in addition to other major integrase inhibitor drug resistance mutations. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I 107 111 IN;IN;INSTI 52;209;167 61;218;172 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. This is the first time that such a high prevalence of L74I mutations has been reported in West African G and AG subtypes, with potential implications for the effectiveness of dolutegravir, which is now being rolled out as part of the first-line treatment in this setting, where there is less frequent viral load monitoring and less access to genotypic resistance testing. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I 54 58 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. This prompted us to evaluate not only major integrase inhibitor mutations, but also L74I. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I 84 88 IN 44 53 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. This would be consistent with a lack of fitness cost of L74I in the absence of drug pressure. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I 56 60 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. Uniquely, in this study we were able to assess the frequency of viral variants with L74I in longitudinal samples from multiple individuals. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I 84 88 32105319 High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. We found over a third of the integrase inhibitor-naive HIV-positive participants in our study had the integrase L74I mutation and that L74I was more common in HIV-1 subtype G than CRF02_AG. 2020 The Journal of antimicrobial chemotherapy Discussion HIV L74I;L74I 112;135 116;139 IN;IN 29;102 38;111 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. In fact, computational modeling of INSTIs resistance development across different HIV-1 subtypes showed that compared to subtype B, the presence of M50I in subtypes A and C, L74I in subtypes A and CRF02_AG, G163R in CRF01_AE, and V165I in subtypes F and CRF01_AE would be associated with lower genetic barrier to resistance in these non-B clades. 2020 International journal of molecular sciences Discussion HIV G163R;L74I;M50I;V165I 207;174;148;230 212;178;152;235 INSTI 35 41 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. In fact, patients harboring viruses with L74M or E157Q mutations in addition to other integrase RAMs showed reduced susceptibility to DTG. 2020 International journal of molecular sciences Discussion HIV E157Q;L74M 49;41 54;45 IN 86 95 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Mutations in integrase aa 155 have been associated with reduced susceptibility to RAL (by 10-fold) and EVG (by 30-fold), and studies of patients failing DTG-based ART showed that patients with virologic failure had N155H substitution at baseline and also developed additional INSTIs-RAMs. 2020 International journal of molecular sciences Discussion HIV N155H 215 220 IN;INSTI 13;276 22;282 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. No INSTIs major RAMs were present in cohort samples, and only 2 database samples had INSTIs major RAMs: T66A in a group M/O recombinant and N155K in a CRF36_cpx sample. 2020 International journal of molecular sciences Discussion HIV N155K;T66A 140;104 145;108 INSTI;INSTI 3;85 9;91 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Several other integrase accessory RAMs and polymorphic mutations were observed in our current study, including the INSTIs accessory RAMs T97A (in 2% of cohort and 7.4% of database samples), E157Q (in 6% of cohort and 1.4% of database samples), A128T (in 0.47% of database samples); the polymorphic mutations M50I (in 6% of cohort and 31% of database samples), S119R (in 4% of cohort and 0.47% of database samples), L74M (in 9% of cohort and 4% of database samples), L74I (in 25% of cohort and 23% of database samples), E138D (in 0.47% database samples), and S230N (in 0.93% of database samples). 2020 International journal of molecular sciences Discussion HIV A128T;E138D;E157Q;L74I;L74M;M50I;S119R;S230N;T97A 244;519;190;466;415;308;360;558;137 249;524;195;470;419;312;365;563;141 IN;INSTI 14;115 23;121 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Similarly, although L74M and E157Q individually have minimal effect on the susceptibility to INSTIs, a combination of L74M and E157Q with other INSTIs RAMs result in reduced susceptibility to INSTIs. 2020 International journal of molecular sciences Discussion HIV E157Q;E157Q;L74M;L74M 29;127;20;118 34;132;24;122 INSTI;INSTI;INSTI 93;144;192 99;150;198 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. Six of our subjects (3 cohort and 3 database samples) were infected with viruses that had both I72V and L74M mutations; one cohort sample had both L74M and T97A, and 3 database samples had both I72V and T97A mutations. 2020 International journal of molecular sciences Discussion HIV I72V;I72V;L74M;L74M;T97A;T97A 95;194;104;147;156;203 99;198;108;151;160;207 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. T66A and T66I reduce EVG susceptibility, respectively, by 5-fold and 10-fold. 2020 International journal of molecular sciences Discussion HIV T66I;T66A 9;0 13;4 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. T66K reduced susceptibility to EVG by 40-fold, reduced susceptibility to RAL by 10-fold, and reduced susceptibility to DTG by 2- to 3-fold. 2020 International journal of molecular sciences Discussion HIV T66K 0 4 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. T97A mutation can reduce EVG susceptibility by 3-fold, and combination of T97A substitution with other INSTIs RAMs markedly reduce HIV susceptibility to RAL and DTG. 2020 International journal of molecular sciences Discussion HIV T97A;T97A 74;0 78;4 INSTI 103 109 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The aa substitutions E92Q, S119R, E138A, Y143R, G148H/R, and S230R/N are more prevalent in subtype-B than in non-B subtypes, whereas mutations such as L74I/M, T97A, L101I, E157Q, T214A, and V201I are more prevalent in non-B subtypes compared to HIV-1 subtype B. 2020 International journal of molecular sciences Discussion HIV E138A;E157Q;E92Q;G148H;G148R;L101I;L74I;L74M;S119R;S230N;S230R;T214A;T97A;V201I;Y143R 34;172;21;48;48;165;151;151;27;61;61;179;159;190;41 39;177;25;55;55;170;157;157;32;68;68;184;163;195;46 32106437 Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy. The other mutation (S230N) was in the C-terminal domain, a region that helps stabilize the integrase-viral DNA complex. 2020 International journal of molecular sciences Discussion HIV S230N 20 25 IN 91 100 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. In the current study, HIV-1 SDRMs (D67N and D67E) belonging to the NRTIs class were found in two subjects and SDRMs) K103N and V106A (belonging to the NNRTIs class were found in three subjects. 2020 PloS one Discussion HIV D67E;D67N;K103N;V106A 44;35;115;127 48;40;122;132 NNRTI;NRTI 151;67 157;72 32119691 HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. M46I and I47V were the most frequent mutations for PIs; M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. 2020 PloS one Discussion HIV I47V;K103N;K103S;M184V;M46I 9;110;110;56;0 13;117;117;61;4 NNRTI;NRTI;PI 151;99;51 157;104;54 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. As a result of substitutions N169D + K187E + S190N at V2 sites and A389T at a V4 site, the PGR epitope of KD247 at the apex of the V3 area might be under the V1V2 site (Figure 8b). 2020 Pathogens (Basel, Switzerland) Discussion HIV A389T;K187E;N169D;S190N 67;37;29;45 72;42;34;50 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. In addition, S190N+A389T can also increase the stability. 2020 Pathogens (Basel, Switzerland) Discussion HIV A389T;S190N 19;13 24;18 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. In comparison, the substitutions in the V2 region resulted in changes in two electrical charges (N169D and K187E) and one N-linked glycosylation site (S190N) (Figure 1). 2020 Pathogens (Basel, Switzerland) Discussion HIV K187E;N169D;S190N 107;97;151 112;103;156 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. In summary, we speculate that negative charges, such as N169D (aspartic acid) and K187E, can alter the MK1 Env conformation so that the V3 region is buried. 2020 Pathogens (Basel, Switzerland) Discussion HIV K187E;N169D 82;56 87;61 Env 107 110 32138199 Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance. The asparagine (N) at position 386 in HXB2 gp120, which corresponds to the N at position 387 in MK1, is not essential for protein folding or function, but is involved in immune evasion. 2020 Pathogens (Basel, Switzerland) Discussion HIV N386N 0 37 gp120 43 48 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. A92E displayed different behavior than what we have previously observed. 2020 Virology journal Discussion HIV A92E 0 4 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. A92E has been implicated in infection of nondividing cells and altered use the cellular factor cyclophilin A for HIV infection. 2020 Virology journal Discussion HIV A92E 0 4 HIV infections 113 126 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. also found that E45A/R132T virus had less capsid disassembly compared to wildtype in an in vitro uncoating assay which may seem to contradict our results. 2020 Virology journal Discussion HIV E45A;R132T 16;21 20;26 Capsid 42 48 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. As widespread structural changes are not observed in E45A or R132T mutant viruses, the altered chemical natures of these side chains were proposed to account for the effects of the mutations on replication. 2020 Virology journal Discussion HIV E45A;R132T 53;61 57;66 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Because the uncoating of each virus is normalized independently, different sensitivities of wildtype and N74D virus to CsA could impact uncoating kinetics if this sensitivity changes over the time course of the assay. 2020 Virology journal Discussion HIV N74D 105 109 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Compared to the carrier control ethanol, CsA treatment decreased the infectivity of both wildtype and N74D mutant virus in CHME3 cells. 2020 Virology journal Discussion HIV N74D 102 106 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. E45A virus was also observed to uncoat slower than wildtype in fluorescence microscopy based uncoating assays. 2020 Virology journal Discussion HIV E45A 0 4 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Given the species difference between OMK and human cell lines, it is possible that A92E necessitates the use of different cellular factors, thus resulting in a differential effect of this mutation between cell lines. 2020 Virology journal Discussion HIV A92E 83 87 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. However, CsA treatment has been shown to decrease infectivity of N74D virus by ~ 2-3-fold in HeLa cells, whereas wildtype infectivity was slightly increased. 2020 Virology journal Discussion HIV N74D 65 69 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. However, E45A/R132T virus still had a hyperstable capsid. 2020 Virology journal Discussion HIV E45A;R132T 9;14 13;19 Capsid 50 56 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. In CHME3 cells N74D mutant virus uncoated with a half-life of 141 min compared to a half-life of 62 min for wildtype in the parallel assays. 2020 Virology journal Discussion HIV N74D 15 19 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. In the absence of cellular factors E45A/R132T virus likely uncoated slower than wildtype and with a similar efficiency as E45A virus due to its increased capsid stability. 2020 Virology journal Discussion HIV E45A;E45A;R132T 35;122;40 39;126;45 Capsid 154 160 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. In the CsA washout assay E45A/R132T virus uncoated at a rate that was not significantly different from wildtype because this assay is performed in cells which would allow interactions with cellular factors to impact uncoating. 2020 Virology journal Discussion HIV E45A;R132T 25;30 29;35 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. In the CsA washout assay, the E45A mutation slowed the rate of uncoating in CHME3 cells with an increased half-life of 102 min compared to the wildtype control. 2020 Virology journal Discussion HIV E45A 30 34 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. In this study the N74D mutation also prevented NUP358 and Kif5B from binding to the HIV capsid. 2020 Virology journal Discussion HIV N74D 18 22 Capsid 88 94 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. In this study, the R132T compensatory mutation partially rescued infectivity and nuclear import defects of E45A mutant virus. 2020 Virology journal Discussion HIV E45A;R132T 107;19 111;24 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Like the N74D mutation, this mutation also results in the use of an alternate nuclear import pathway than that mediated by TNPO3, CPSF6, and NUP358. 2020 Virology journal Discussion HIV N74D 9 13 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. N74D and E45A significantly altered the rate of uncoating compared to the parallel HIV-GFP control in CHME3 cells. 2020 Virology journal Discussion HIV E45A;N74D 9;0 13;4 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. R132T is a second site suppressor mutation that was isolated from serial passage of E45A mutant virus in culture. 2020 Virology journal Discussion HIV E45A;R132T 84;0 88;5 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. showed that the R132T mutation restored the ability of E45A virus to bind the drug PF74. 2020 Virology journal Discussion HIV E45A;R132T 55;16 59;21 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Surprisingly, we found that E45A/R132T virus uncoated with kinetics similar to wildtype. 2020 Virology journal Discussion HIV E45A;R132T 28;33 32;38 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The E45A mutation produces a hyperstable capsid lattice with increased stiffness in atomic force microscopy assays. 2020 Virology journal Discussion HIV E45A 4 8 Capsid 41 47 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The N74D mutation causes HIV to utilize a different nuclear import pathway than that mediated by the importin-beta protein TNPO3, nucleocytoplasmic shuttle protein CPSF6, and nucleoporin NUP358. 2020 Virology journal Discussion HIV N74D 4 8 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The N74D, E45A, and A92E mutants were chosen because they significantly altered the rate of uncoating in OMK cells in our previous study. 2020 Virology journal Discussion HIV A92E;E45A;N74D 20;10;4 24;14;8 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. The R132T mutation may restore an interaction surface needed for uncoating, and disruption of this region by the E45A mutation would result in delayed uncoating. 2020 Virology journal Discussion HIV E45A;R132T 113;4 117;9 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Therefore, a likely hypothesis is that the delayed uncoating kinetics of N74D mutant virus in CHME3 cells is due to the inability of this mutant to bind Kif5B or NUP358. 2020 Virology journal Discussion HIV N74D 73 77 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Therefore, in CHME3 cells sensitivity to CsA should not bias the uncoating kinetics for wildtype or N74D virus as determined by the CsA washout assay. 2020 Virology journal Discussion HIV N74D 100 104 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Therefore, the alterations in uncoating for E45A and N74D virus were not due to alterations in reverse transcription. 2020 Virology journal Discussion HIV E45A;N74D 44;53 48;57 RT 95 116 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Therefore, the delayed uncoating kinetics observed in E45A virus were not due to a hyperstable capsid. 2020 Virology journal Discussion HIV E45A 54 58 Capsid 95 101 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. Therefore, we performed a CsA washout assay in the parent CHME3 cell line to determine the kinetics of CsA sensitivity in N74D and wildtype viruses. 2020 Virology journal Discussion HIV N74D 122 126 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. This ~ 2-fold change in uncoating kinetics is most similar to results in HeLa cells, while in OMK cells the N74D mutation only increased that half-life of uncoating by 50%. 2020 Virology journal Discussion HIV N74D 108 112 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. This decrease was greater for wildtype virus compared to N74D mutant virus. 2020 Virology journal Discussion HIV N74D 57 61 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. This result indicates that the contribution of reverse transcription to uncoating occurs before the effect of the N74D and E45A capsid mutations. 2020 Virology journal Discussion HIV E45A;N74D 123;114 127;118 RT;Capsid 47;128 68;134 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. This result is similar to our previous study, although there was a more modest delay in uncoating due to the E45A mutation in OMK cells. 2020 Virology journal Discussion HIV E45A 109 113 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. This result is similar to what was previously found in OMK cells for the E45A, N74D, and A92E mutations. 2020 Virology journal Discussion HIV A92E;E45A;N74D 89;73;79 93;77;83 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. To determine whether capsid stability or disrupted interaction with cellular factors was responsible for the delayed uncoating of E45A mutant virus, we examined the uncoating kinetics of the E45A/R123T double mutant virus. 2020 Virology journal Discussion HIV E45A;E45A;R123T 130;191;196 134;195;201 Capsid 21 27 32143686 Characterization of HIV-1 uncoating in human microglial cell lines. While the N74D mutation delayed uncoating in CHME3 cells, there are differences in the magnitude of this change compared to our previous studies. 2020 Virology journal Discussion HIV N74D 10 14 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. Although M184V/I causes high-level in vitro resistance to 3TC, M184V/I is not a contraindication to continued treatment with 3TC because it increases susceptibility to AZT, and in addition, it is associated with clinically significant reductions in HIV-1 replication. 2020 Virology journal Discussion HIV M184I;M184I;M184V;M184V 9;63;9;63 16;70;16;70 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. G190A caused high-level resistance to NVP and intermediate resistance to EFV and could result in attenuation of the resistance that occurs with K103N alone, and G190A had a higher frequency (83.47%) of drug resistance in the HIV-1 CRF 01AE subtype in this study. 2020 Virology journal Discussion HIV G190A;K103N;G190A 161;144;0 166;149;5 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K103N/S (41.32%) was the most frequently observed resistance mutation in NNRTIs, followed by Y181C(27.83%) and G190A(26.21%), This is a consequence of the frequent use of NNRTI-based (EFV/NVP) first-line therapy for more than a decade in China, and these results are similar to the data from low- and middle-income countries. 2020 Virology journal Discussion HIV G190A;K103S;Y181C;K103N 111;0;93;0 116;7;98;7 NNRTI;NNRTI 73;171 79;176 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K103N/S was strongly associated with failure against NVP and EVP. 2020 Virology journal Discussion HIV K103S;K103N 0;0 7;7 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. K65R is the signature mutation associated with TDF resistance. 2020 Virology journal Discussion HIV K65R 0 4 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. Similar to our study finding, a high prevalence of M184 V/I mutation has been reported in Asia, Sub-Saharan Africa and Latin America, but a lower prevalence in western Europe. 2020 Virology journal Discussion HIV M184I;M184V 51;51 59;59 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. The elevated presence of M184V/I is expected and arises as a consequence of the use of 3TC as part of all the first-line regimens in China. 2020 Virology journal Discussion HIV M184I;M184V 25;25 32;32 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. The most frequently identified ADR present in NRTI was M184V/I (61.27%), followed by K65R (19.96%). 2020 Virology journal Discussion HIV K65R;M184I;M184V 85;55;55 89;62;62 NRTI 46 50 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. This study showed that K65R codon mutation had a significant increase from 2014 (71.4, 6.74, 16.42, 22.73%, 20.48 and 30.91%, respectively, from 2012 to 2017), due to the widespread use of TDF replacing AZT and D4T as a part of the first-line treatment from 2014 in China following WHO recommendations. 2020 Virology journal Discussion HIV K65R 23 27 32183889 Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China. Y181C reduces susceptibility to NVP by > 50-fold and to EFV by 2-fold. 2020 Virology journal Discussion HIV Y181C 0 5 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Here, we show that this insensitivity is due to the lack of TRIM5alphahu binding to HIV-1-A92E or HIV-1-G94D mutant cores. 2020 Cell reports Discussion HIV A92E;G94D 90;104 94;108 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. In addition, depletion of TRIM5alphahu expression in CD4+ T cells rescued infectivity of HIV-1-P90A viruses. 2020 Cell reports Discussion HIV P90A 95 99 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. In contrast, infection of primary lymphocytes by HIV-1-A92E or HIV-1-G94D was not affected when compared to that of wild-type HIV-1. 2020 Cell reports Discussion HIV A92E;G94D 55;69 59;73 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Mutant HIV-1 (P90A or G89V) infection of PBMCs or CD4+ T cells was 10-20-fold weaker than that of wild-type HIV-1. 2020 Cell reports Discussion HIV G89V;P90A 22;14 26;19 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Mutations in the CypA-binding loop of the capsid, such as P90A and G89V, cause an infectivity defect similar to that caused by CsA treatment during wild-type HIV-1 infection of Jurkat and CD4+ T cells; however, infection of HIV-1 viruses bearing the capsid change A92E or G94D results in an infection that is insensitive to CsA treatment in Jurkat cells. 2020 Cell reports Discussion HIV A92E;G89V;G94D;P90A 264;67;272;58 268;71;276;62 Capsid;Capsid 42;250 48;256 32187548 Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core. Normal viral infectivity correlated with the inability of TRIM5alphahu to bind to HIV-1-A92E and HIV-1-G94D cores. 2020 Cell reports Discussion HIV A92E;G94D 88;103 92;107 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. Despite modifications, these K65R probes had the highest rate of IND results (8.5%) mainly due to closely spaced nucleotide variations at codons 67, 68, and 69, including the polymorphic mutation S68G (Supplementary Table 3, http://links.lww.com/QAD/B693). 2020 AIDS (London, England) Discussion HIV K65R;S68G 29;196 33;200 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. Further reduction of the overall IND rate could be achieved by including probes for alternative variants at the codons tested, such as M184I and G190S, depending on the frequency of these mutations in the target population. 2020 AIDS (London, England) Discussion HIV G190S;M184I 145;135 150;140 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. In contrast, K103S confers high-level resistance to NVP and intermediate to EFV. 2020 AIDS (London, England) Discussion HIV K103S 13 18 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. K102Q/R, K103R, and K104R have not been associated with reduced susceptibility to NNRTIs, but can interfere with detection of K103N by OLA-Simple, as their presence could interfere with the DNA ligase requirement that the four nucleotides surrounding the ligation site have perfect complementarity with the target, causing an IND result. 2020 AIDS (London, England) Discussion HIV K102Q;K102R;K103N;K103R;K104R 0;0;126;9;20 7;7;131;14;25 NNRTI 82 88 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. Probe design for K103N proved particularly challenging due to relatively frequent changes at this or adjacent codons 102 (K102Q/R), 103 (K103S, K103R), and 104 (K104R). 2020 AIDS (London, England) Discussion HIV K102Q;K102R;K103N;K103R;K103S;K104R 122;122;17;144;137;161 129;129;22;149;142;166 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. The subtype B-specific probes tested in this study reduced the combined IND rate at codons K103N/S, Y181C, M184V, and G190A to 1.3% (3/236) from a 2.7% IND rate observed when using probes designed to work 'universally' across multiple HIV-1 group M subtypes, and tested on specimens from Kenya, South Africa, Peru, and Thailand. 2020 AIDS (London, England) Discussion HIV G190A;K103N;K103S;M184V;Y181C 118;91;91;107;100 123;98;98;112;105 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. Therefore, probes detecting both K103N and K103S were tested simultaneously in this updated OLA-Simple kit by mixing four genotype-specific probes and one common probe, resulting in no IND results at K103N/S in this cohort. 2020 AIDS (London, England) Discussion HIV K103N;K103N;K103S;K103S 33;200;200;43 38;207;207;48 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. To reduce the IND rate for K65R, a mixture of common probes complementary to these polymorphisms/mutations may be necessary at this site. 2020 AIDS (London, England) Discussion HIV K65R 27 31 32205723 Near point-of-care, point-mutation test to detect drug resistance in HIV-1: a validation study in a Mexican cohort. Universal probes for K65R in the OLA-Simple kit were slightly modified for the subtype B Mexican variants, and these had not been previously validated on clinical specimens. 2020 AIDS (London, England) Discussion HIV K65R 21 25 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. At the same time there is a significant reduction in the correlations involving some residue pairs as described above and the Ab-bound, RIT-bound and G40E/G40R mutated proteases adopt the closed inactive conformation. 2020 Scientific reports Discussion HIV G40E;G40R 150;155 154;159 PR 168 177 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. For example, Ile50 of chain A forms hydrophobic contact with Ile84 of chain B for about 95% of the time in Ab-bound and G40E mutant protease and about 86% of the time in G40R protease. 2020 Scientific reports Discussion HIV G40E;G40R 120;170 124;174 PR;PR 132;175 140;183 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. In G40E and G40R mutants also, the single mutation (G40E/G40R) in elbow region of both the monomers causes the protease dimer to rigidified and the opening of the flap region is restricted. 2020 Scientific reports Discussion HIV G40E;G40E;G40R;G40R 3;52;12;57 7;56;16;61 PR 111 119 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Similarly, Ile54 of chain A forms hydrophobic contact with Ile50 of chain B for about 95% of the time in Ab-bound, G40R and G40E protease simulations and 88% of the tine in RIT-bound protease simulation. 2020 Scientific reports Discussion HIV G40E;G40R 124;115 128;119 PR;PR 129;183 137;191 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. tested the role of flexibility in protease activity by constructing two protease variants by introducing a pair of cysteines (G16C/L38C and R14C/E65C) at the interfaces of flexible regions remote from the active site in both the chains of protease. 2020 Scientific reports Discussion HIV E65C;G16C;L38C;R14C 145;126;131;140 149;130;135;144 PR;PR;PR 34;72;239 42;80;247 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. The introduction of disulfide bonds decreases the flexibility and lowers the enzyme activity by 146 fold in G16C/L38C variant. 2020 Scientific reports Discussion HIV G16C;L38C 108;113 112;117 32218488 Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations. Through internal hydrogen-bonding and salt-bridges network analysis in WT-free, RIT-bound, Ab-bound and mutant proteases (G40E and G40R) simulations, we find a significant rearrangement of hydrogen-bonding interactions and salt-bridges in protease due to mutation and Ab/RIT binding. 2020 Scientific reports Discussion HIV G40E;G40R 122;131 127;135 PR;PR 111;239 120;247 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. A study has shown that eight patients who had the E157Q mutation and were initiated with DTG-based therapy did not experience viremia suppression below detection level. 2020 Frontiers in microbiology Discussion HIV E157Q 50 55 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Furthermore, our data suggest that EVG activity is compromised in the presence of any RAL RAM, in this case Y143R. 2020 Frontiers in microbiology Discussion HIV Y143R 108 113 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Furthermore, these findings are in agreement with that observed both V82A and M46I has the most common mutation in infected children receiving PI-based cART. 2020 Frontiers in microbiology Discussion HIV M46I;V82A 78;69 82;73 PI 143 145 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Furthermore, we identified the presence of T66I mutation in 1 (1%) patient. 2020 Frontiers in microbiology Discussion HIV T66I 43 47 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. In a previous study conducted by, we also found E157Q on HIV-1-infected South African sequences retrieved from the HIV database. 2020 Frontiers in microbiology Discussion HIV E157Q 48 53 HIV infections 57 71 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. In our study, M184V, L74V, K65R, and Y115F were the most common major NRTI RAMs in patients receiving LPV/r as their bPIs. 2020 Frontiers in microbiology Discussion HIV K65R;L74V;M184V;Y115F 27;21;14;37 31;25;19;42 NRTI 70 74 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. M184V, the most common NRTI RAM, occurred more frequently in patients receiving AZT plus 3TC, in comparison with patients receiving the ABC plus 3TC regimen. 2020 Frontiers in microbiology Discussion HIV M184V 0 5 NRTI 23 27 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. N155H, Q148H/R/K, and Y143R/C/H are the three major recognized pathways of genotypic resistance against InSTIs. 2020 Frontiers in microbiology Discussion HIV Q148H;Q148K;Q148R;Y143C;Y143H;Y143R;N155H 7;7;7;22;22;22;0 16;16;16;31;31;31;5 INSTI 104 110 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Our findings also showed M46I and V82A RAMs as the most prevalent major PI RAMs. 2020 Frontiers in microbiology Discussion HIV M46I;V82A 25;34 29;38 PI 72 74 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Our findings are in agreement with study where major PI RAMs were observed in 5% of patients; among them, V82A 65% (28/43), I54V 63% (27/43), L76V 23% (10/43), and L90M 16% (7/43) were the most frequent. 2020 Frontiers in microbiology Discussion HIV I54V;L76V;L90M;V82A 124;142;164;106 128;146;168;110 PI 53 55 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Our findings correspond with previous studies conducted in South Africa with PLHIV, showing M184V/I as the most prevalent NRTI mutation. 2020 Frontiers in microbiology Discussion HIV M184I;M184V 92;92 99;99 NRTI 122 126 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. T66I confers low-level resistance to RAL and high-level resistance to EVG. 2020 Frontiers in microbiology Discussion HIV T66I 0 4 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The group receiving AZT plus 3TC or ABC plus 3TC showed the highest rate of PIs such as I54V, I84V, L76V, I47A/V, I50L/V, and V32I. 2020 Frontiers in microbiology Discussion HIV I47A;I47V;I50L;I50V;I54V;I84V;L76V;V32I 106;106;114;114;88;94;100;126 112;112;120;120;92;98;104;130 PI 76 79 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The group receiving AZT plus 3TC or ABC plus 3TC showed the highest rates of NNRTI mutations such as P225H, V106M, E138A/G/K/Q, G190A/S, and Y188L occurred most frequently in patients receiving AZT plus 3TC or ABC plus 3TC. 2020 Frontiers in microbiology Discussion HIV E138A;E138G;E138K;E138Q;G190A;G190S;P225H;V106M;Y188L 115;115;115;115;128;128;101;108;141 126;126;126;126;135;135;106;113;146 NNRTI 77 82 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The high rate of K103N RAM is also well documented and has been observed in several previous studies. 2020 Frontiers in microbiology Discussion HIV K103N 17 22 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The K103N mutation occurred at a higher frequency in patients receiving AZT plus 3TC or ABC plus 3TC than in those receiving TDF plus 3TC, and 3TC plus d4T. 2020 Frontiers in microbiology Discussion HIV K103N 4 9 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The K65R and Y115F RAMs occurred more frequently in patients receiving AZT plus 3TC, rather than in patients receiving ABC plus 3TC. 2020 Frontiers in microbiology Discussion HIV K65R;Y115F 4;13 8;18 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The M46I and V82A RAMs were the most common mutations observed in patients receiving LPV/r compared with ATV/r. 2020 Frontiers in microbiology Discussion HIV M46I;V82A 4;13 8;17 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The most common PI RAM reported by was M46I 28 (33%), followed by I50V 18 (21%) and V82A 18 (21%). 2020 Frontiers in microbiology Discussion HIV I50V;M46I;V82A 66;39;84 70;43;88 PI 16 18 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. The most frequent TAM was K70R/E, which occurred mostly in patients receiving AZT plus 3TC, as opposed to ABC plus 3TC and FTC plus TDF. 2020 Frontiers in microbiology Discussion HIV K70E;K70R 26;26 32;32 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Viruses having E157Q were found to be associated with treatment failure of a DTG-containing regimen. 2020 Frontiers in microbiology Discussion HIV E157Q 15 20 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. We also identified the presence of E157Q in 2 (2%) patients. 2020 Frontiers in microbiology Discussion HIV E157Q 35 40 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. We confirmed Y143R in our study and this mutation in combination with T97A also impaired EVG susceptibility and showed possible low-level resistance. 2020 Frontiers in microbiology Discussion HIV T97A;Y143R 70;13 74;18 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. We identified a low frequency of M46I and V82A in patients receiving ATV/r as their bPIs. 2020 Frontiers in microbiology Discussion HIV M46I;V82A 33;42 37;46 32265875 Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. We observed the presence of Y143R in combination with T97A in one of our patients receiving ABC, 3TC, LPV/r. 2020 Frontiers in microbiology Discussion HIV T97A;Y143R 54;28 58;33 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. A study on PI-naive Nigerian HIV-patients have earlier identified I13V, M36I and H69K as wild-type consensus mutations for HIV-1 subtypes G', G, CRF02_AG, CRF06_cpx, and A. 2020 PloS one Discussion HIV H69K;I13V;M36I 81;66;72 85;70;76 PI 11 13 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Although our study did not determine the phenotypic resistance pattern in the infected individuals (a limitation of the study), analysis according to the Stanford algorithm showed that M46L mutation confers potential low-level resistance to ATV/r, FPV/r, IDV/r, LPV/r, TPV/r and intermediate-level resistance to NFV to isolates in this study as shown in Table 3. 2020 PloS one Discussion HIV M46L 185 189 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. I13V/A, K20I, M36I/L, R41K, H69K/R and L89M are the consensus mutations identified for subtypes G, UG and CRF02_AG while E35Q, R57K/G, C67E/S and V82I are the consensus mutations for G and UG in this study. 2020 PloS one Discussion HIV C67E;C67S;E35Q;H69K;H69R;I13A;I13V;K20I;L89M;M36I;M36L;R41K;R57G;R57K;V82I 135;135;121;28;28;0;0;8;39;14;14;22;127;127;146 141;141;125;34;34;6;6;12;43;20;20;26;133;133;150 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. In addition, the mutations K14R, N37D/S/E/H and L63T/P/S/Q occurred in >= 25% of subtype G, UG and CRF02_AG patients, at a proportion that is significantly greater than in subtype B. 2020 PloS one Discussion HIV K14R;L63P;L63Q;L63S;L63T;N37D;N37E;N37H;N37S 27;48;48;48;48;33;33;33;33 31;58;58;58;58;43;43;43;43 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. In line with this, the only isolate with V82L mutation in this study, NG_IM.12_07, also harbours N88D mutation in addition to L10I and K20I mutations. 2020 PloS one Discussion HIV K20I;L10I;N88D;V82L 135;126;97;41 139;130;101;45 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. M46I/L is a nonpolymorphic PI-selected mutation that reduces susceptibility to indinavir (IDV), nelfinavir (NFV), fosamprenavir (FPV), lopinavir (LPV) and atazanavir (ATV) when present with other mutations. 2020 PloS one Discussion HIV M46I;M46L 0;0 6;6 PI 27 29 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. M46L also reduces susceptibility to tipranavir (TPV). 2020 PloS one Discussion HIV M46L 0 4 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Other mutations/polymorphisms that occurred at very high frequencies among patients in this study include; I13V/A, K20I, E35Q, M36I/L, R41K, R57K/G, L63T/P/S/Q, C67E/S, H69K/R, V82I and L89M. 2020 PloS one Discussion HIV C67E;C67S;E35Q;H69K;H69R;I13A;I13V;K20I;L63P;L63Q;L63S;L63T;L89M;M36I;M36L;R41K;R57G;R57K;V82I 161;161;121;169;169;107;107;115;149;149;149;149;186;127;127;135;141;141;177 167;167;125;175;175;113;113;119;159;159;159;159;190;133;133;139;147;147;181 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Our study also revealed very high frequencies of minor mutations in the protease gene of the isolates with the predominant mutations found at positions L10I/V and K20I. 2020 PloS one Discussion HIV K20I;L10I;L10V 163;152;152 167;158;158 PR 72 80 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. Similarly, mutations L10V/I, L19P, E35D, I64L/M and K70R occurred in >= 25% of CRF02_AG patients at a proportion that is significantly greater than in subtype B in this study. 2020 PloS one Discussion HIV E35D;I64L;I64M;K70R;L10I;L10V;L19P 35;41;41;52;21;21;29 39;47;47;56;27;27;33 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. The frequency of occurrence (10.7%) of major PI resistance mutations, M46L and V82L, obtained in this study is somewhat lower than the 39.1% recorded in a similar study conducted by Odaibo et al. 2020 PloS one Discussion HIV M46L;V82L 70;79 74;83 PI 45 47 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. The only isolate with intermediate-level resistance to these drugs had V82L major PI resistance mutation as well as L10I and N88D minor PI resistance mutations. 2020 PloS one Discussion HIV L10I;N88D;V82L 116;125;71 120;129;75 PI;PI 82;136 84;138 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. The same study also identified K20I as consensus for G', G, CRF02_AG, and CRF06_cpx while V82I was identified as the consensus for G' and G. 2020 PloS one Discussion HIV K20I;V82I 31;90 35;94 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. This V82L mutation is shown to confer low-level resistance to ATV/r, FPV/r and SQV/r as well as potential low-level resistance to IDV/r and LPV/r while it confers intermediate-level resistance to NFV and TPV/r. 2020 PloS one Discussion HIV V82L 5 9 32267869 Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. V82L is an uncommon non-polymorphic substrate-cleft mutation known to reduce susceptibility to TPV. 2020 PloS one Discussion HIV V82L 0 4 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. In our study, M184I/V (59.59%) was the most prevalent mutation associated with NRTI resistance in our study and was also frequently found in Europe, Africa, and other regions in China. 2020 BioMed research international Discussion HIV M184I;M184V 14;14 21;21 NRTI 79 83 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. In this study, among the PI-associated DR mutations detected, K20I/R and T74S were mainly found in CRF01_AE while A71I/T/V, Q58E, and V82I were frequently observed in CRF07_BC, indicating that the presence of different mutations may vary among different subtypes. 2020 BioMed research international Discussion HIV A71I;A71T;A71V;K20I;K20R;Q58E;T74S;V82I 114;114;114;62;62;124;73;134 122;122;122;68;68;128;77;138 PI 25 27 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. K101 E/H/P, Y181 C/V, and G190 A/E/K/Q/S/V are broad spectrum general mutations resistant to all NNRTIs. 2020 BioMed research international Discussion HIV G190A;G190E;K101E;K101H;Y181C;Y181V 26;26;0;0;12;12 42;42;10;10;20;20 NNRTI 97 103 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. K65R is one of the mutations with broad-spectrum resistance and was found in more than one-quarter of the cases. 2020 BioMed research international Discussion HIV K65R 0 4 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. NRTI-associated DRMs M184I/V and K65R and NNRTI-associated DRMs with extensively drug resistance K101E/H/P, V179I/D/E/T, Y181C/V, and G190A/E/K/Q/S/V were detected in CRF55_01B. 2020 BioMed research international Discussion HIV G190A;G190E;G190K;G190Q;G190S;G190V;K101E;K101H;K101P;K65R;M184I;M184V;V179D;V179E;V179I;V179T;Y181C;Y181V 134;134;134;134;134;134;97;97;97;33;21;21;108;108;108;108;121;121 149;149;149;149;149;149;106;106;106;37;28;28;119;119;119;119;128;128 NNRTI;NRTI 42;0 47;4 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. PI-associated mutations were found in 97 cases, most of which were secondary mutations like L10I/V, A71I/T/V, and K20I/R, so, there were relatively few cases of DR. 2020 BioMed research international Discussion HIV A71I;A71T;A71V;K20I;K20R;L10I;L10V 100;100;100;114;114;92;92 108;108;108;120;120;98;98 PI 0 2 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. The L100I and M230L mutations (4.08%) had low incidence and intermediate or high resistance to RPV and ETR but no resistance to the first-line drugs EFV and NVP. 2020 BioMed research international Discussion HIV L100I;M230L 4;14 9;19 32280691 HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016. Three primary mutations M46I, I47A, and I50V resistant to PIs were detected in one patient, whose regimen was 3TC+AZT+NVP then switched to LPV/r+3TC+TDF. 2020 BioMed research international Discussion HIV I47A;I50V;M46I 30;40;24 34;44;28 PI 58 61 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. A second possibility is that TRIM34 stabilizes TRIM5alpha, thereby allowing it to restrict N74D capsids. 2020 PLoS pathogens Discussion HIV N74D 91 95 Capsid 96 103 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Finally, TRIM34 and TRIM5alpha colocalize in cells and preferentially localize to restricted N74D capsids as compared to WT capsids. 2020 PLoS pathogens Discussion HIV N74D 93 97 Capsid;Capsid 98;124 105;131 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. First, it is possible that TRIM34 changes the specificity of TRIM5alpha such that it can now recognize the N74D capsid mutant virus better and/or more efficiently. 2020 PLoS pathogens Discussion HIV N74D 107 111 Capsid 112 118 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Further, TRIM34 may act more broadly across primates to restrict lentiviral infection, as rhesus macaque TRIM34 similarly blocks N74D replication (Fig 3G). 2020 PLoS pathogens Discussion HIV N74D 129 133 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. However, conflicting data shows that the N74D capsid mutant has been reported to have the same intrinsic stability as the WT capsid as measured by an in vitro uncoating assay. 2020 PLoS pathogens Discussion HIV N74D 41 45 Capsid;Capsid 46;125 52;131 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. However, since the N74D mutation has pleiotropic effects, this rescue of the N74D mutant could also be independent of TRIM34. 2020 PLoS pathogens Discussion HIV N74D;N74D 19;77 23;81 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. However, this effect is independent of CPSF6 binding to capsids as loss of binding to CPSF6 is not sufficient for restriction by TRIM34 (see the A77V mutant in Fig 3A and 3B and the N57A mutant in Fig 3C). 2020 PLoS pathogens Discussion HIV A77V;N57A 145;182 149;186 Capsid 56 63 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. In support of this model, slower uncoating kinetics of the N74D capsid mutant have been observed. 2020 PLoS pathogens Discussion HIV N74D 59 63 Capsid 64 70 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Instead, it may be that the TRIM34 SPRY does not itself make significant contact with the N74D capsid but that TRIM34 complexing with TRIM5alpha may affect recognition of this capsid specifically by human TRIM5alpha. 2020 PLoS pathogens Discussion HIV N74D 90 94 Capsid;Capsid 95;176 101;182 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Our data suggest that TRIM34, together with TRIM5alpha, mediates all or most of the block to replication of the N74D capsid mutant observed in primary cells, including CD4+ T cells and MDMs, first described by Ambrose et al. 2020 PLoS pathogens Discussion HIV N74D 112 116 Capsid 117 123 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Our screen with P90A did not uncover any additional factors, other than TRIM5alpha, suggesting that the increased IFN sensitivity of this mutant is entirely due to TRIM5alpha restriction. 2020 PLoS pathogens Discussion HIV P90A 16 20 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. Previously, modest restriction of SIVmac and the non-primate lentivirus, Equine Infectious Anemia Virus (EIAV), by human TRIM34 was described but no effect of TRIM34 was observed on either WT HIV-1 or a G89V capsid mutant virus. 2020 PLoS pathogens Discussion HIV G89V 203 207 Capsid 208 214 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. The N74D capsid mutant has been proposed to trigger sensing pathways leading to IFN and other cytokine production in macrophages although this phenotype of sensing of the N74D mutant occurs in macrophages has been challenged. 2020 PLoS pathogens Discussion HIV N74D;N74D 4;171 8;175 Capsid 9 15 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. This dependence of TRIM34 on TRIM5alpha raises several key questions including: 1) how does TRIM34 allow for specific restriction of the N74D capsid mutant viruses? and 2) why does this restriction depend on TRIM5alpha? We propose two potential models that are consistent with our data that are not mutually exclusive. 2020 PLoS pathogens Discussion HIV N74D 137 141 Capsid 142 148 32282853 TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner. While we did not identify here the factor responsible for enhanced sensitivity of the N74D mutant to IFN, we do uncover IFN-independent restriction by a novel capsid-targeting restriction factor, TRIM34. 2020 PLoS pathogens Discussion HIV N74D 86 90 Capsid 159 165 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. A62VRT is observed in two unusual mutational patterns: the Q151M complex and the T69SSS insertion complex. 2020 Viruses Discussion HIV A62V;Q151M;T69SSS 0;59;81 6;64;87 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. Conversely, G190S development in A6 isolates is significantly higher (up to 30% to 60%) after EFV and/or nevirapine (NVP)-exposure and is favoured over the K103N and Y181C resistance pathways. 2020 Viruses Discussion HIV G190S;K103N;Y181C 12;156;166 17;161;171 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. In A6 samples, A62VRT is an endemic polymorphism with similarly high prevalence among TN and TE patients. 2020 Viruses Discussion HIV A62V 15 21 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. In non-A6 isolates, K103NRT or Y181CRT are preferentially detected after efavirenz exposure while G190SRT is rarely observed, probably due to high costs in replication capacity (in the subtype B context, 20% compared to the wt). 2020 Viruses Discussion HIV G190S;K103N;Y181C 98;20;31 105;27;38 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. In subtype B, A62VRT is a compensatory mutation associated with NRTI-class resistance. 2020 Viruses Discussion HIV A62V 14 20 NRTI 64 68 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. Our analysis detected two specific RAMs significantly associated to A6 viruses: A62VRT and G190SRT. 2020 Viruses Discussion HIV A62V;G190S 80;91 86;98 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. The A62VRT alone is rare in subtype B, TN-samples as it reduces the replication capacity of these variants to 50% compared to the wild type (wt) virus. 2020 Viruses Discussion HIV A62V 4 10 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. The effect of G190SRT in replication capacity of A6 isolates is yet to be analysed. 2020 Viruses Discussion HIV G190S 14 21 32331438 HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia. The substitution G190SRT confers high level resistance against doravirine, efavirenz, and nevirapine and reduces etravirine and rilpivirine susceptibility to levels of still unknown clinical relevance. 2020 Viruses Discussion HIV G190S 17 24 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Another important observation was that K103R/V179D mutations were exclusively present in the MSM population and distributed in different provinces. 2020 BMC infectious diseases Discussion HIV K103R;V179D 39;45 44;50 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. E138A could have an impact on treatment or prevention strategies that include ETR or RPV in geographic areas where subtype C infection is dominating. 2020 BMC infectious diseases Discussion HIV E138A 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. E138A is also a polymorphic mutation and reduces ETR and RPV susceptibility by about 2-fold. 2020 BMC infectious diseases Discussion HIV E138A 0 5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Except for K103R plus V179D, two new combinations of K103R plus V179E and E138A plus V179D were identified in two drug-naive patients. 2020 BMC infectious diseases Discussion HIV E138A;K103R;K103R;V179D;V179D;V179E 74;11;53;22;85;64 79;16;58;27;90;69 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Firstly, one possible reason is that a subtype C parental strain containing V179D mutation was involved in the recombination event, which resulted in the presence of V179D in the founder CRF65_cpx strain. 2020 BMC infectious diseases Discussion HIV V179D;V179D 76;166 81;171 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. For example, combinations of K103R plus V179D and V106I plus V179D confer intermediate and low reduction in EFV and NVP susceptibility, respectively. 2020 BMC infectious diseases Discussion HIV K103R;V106I;V179D;V179D 29;50;40;61 34;55;45;66 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. However, among the 32 patients harboring CRF65_cpx strains, seven patients had the K103R/V179D mutation, illustrating the surprisingly high prevalence of K103R/V179D in CRF65_cpx strains (21.9%, 7/32). 2020 BMC infectious diseases Discussion HIV K103R;K103R;V179D;V179D 83;154;89;160 88;159;94;165 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. In a recent study, only three isolates had the mutations K103R/V179D in a dataset containing more than 1700 isolates, which showed that the prevalence of K103R/V179D was extremely low. 2020 BMC infectious diseases Discussion HIV K103R;K103R;V179D;V179D 57;154;63;160 62;159;68;165 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. In other words, the sequence of events was as follows: generation of CRF65_cpx, acquisition of V179D mutation, and propagation of CRF65_cpx. 2020 BMC infectious diseases Discussion HIV V179D 95 100 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Interestingly, Giannini and colleagues found that E138A can contribute to reduced response to ETR through a decreased genetic barrier to resistance, indicating the distinct mechanism of E138A resistance to ETR. 2020 BMC infectious diseases Discussion HIV E138A;E138A 50;186 55;191 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. It has been demonstrated that the V179D mutation, conferring potential low-level resistance to NNRTIs, occurred most frequently in CRF01_AE and subtype F viruses, at a rate not greater than 5%. 2020 BMC infectious diseases Discussion HIV V179D 34 39 NNRTI 95 101 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. It was reported that E138A is more prevalent in subtype C than in subtype B in different databases. 2020 BMC infectious diseases Discussion HIV E138A 21 26 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. K103R/V179D mutation was not frequently detected because of the low occurrence of both K103R and V179D in untreated persons. 2020 BMC infectious diseases Discussion HIV K103R;V179D;V179D;K103R 87;6;97;0 92;11;102;5 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. More importantly, these seven sequences were exclusively distributed among MSM group and MSM cluster III, which resulted in a much higher prevalence of K103R/V179D. 2020 BMC infectious diseases Discussion HIV K103R;V179D 152;158 157;163 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Obviously, a founder effect resulted in the presence of V179D in CRF65_cpx, and K103R subsequently emerged in some strains after CRF65_cpx spread to MSM population. 2020 BMC infectious diseases Discussion HIV K103R;V179D 80;56 85;61 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Our study showed that almost all CRF65_cpx strains harbored V179D mutation, and V179D was considered as a signature mutation in CRF65_cpx strains. 2020 BMC infectious diseases Discussion HIV V179D;V179D 60;80 65;85 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Previously, no study reported the presence of V179D in almost all strains of a subtype or CRF. 2020 BMC infectious diseases Discussion HIV V179D 46 51 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Regarding the origin of V179D in CRF65 strain, we think there are two possible reasons. 2020 BMC infectious diseases Discussion HIV V179D 24 29 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Secondly, considering that V179D is a polymorphic mutation, theoretically there is another reason. 2020 BMC infectious diseases Discussion HIV V179D 27 32 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Subsequently, the V179D was transmitted to other patients along with the spread of CRF65_cpx. 2020 BMC infectious diseases Discussion HIV V179D 18 23 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. The combination of K103R and V179E was recommended by the Stanford HIV Drug Resistance Database as likely to reduce NVP and EFV susceptibility as the combination of K103R and V179D. 2020 BMC infectious diseases Discussion HIV K103R;K103R;V179D;V179E 19;165;175;29 24;170;180;34 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. The transmission of CRF65_cpx strains containing K103R/V179D mutation to persons who are treatment naive can compromise the effectiveness of treatment and limit antiretroviral regimen options. 2020 BMC infectious diseases Discussion HIV K103R;V179D 49;55 54;60 32345262 Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains. Together, the impact of K103R/V179E and E138A/V179D on both NNRTI susceptibility and virologic outcome in patients deserves investigation. 2020 BMC infectious diseases Discussion HIV E138A;K103R;V179D;V179E 40;24;46;30 45;29;51;35 NNRTI 60 65 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. A high proportion of drug-resistance mutations was found in ART-naive individuals infected with HIV-1 CRF01_AE and BC recombinants with V179D/T and E138A being the most commonly observed SDRMs. 2020 Infection and drug resistance Discussion HIV E138A;V179D;V179T 148;136;136 153;143;143 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Although V179D/T was more frequently transmitted in ART-naive Burmese individuals, the presence of V179D/T did not intervene with the response to a first-line efavirenz (EFV) containing regimen. 2020 Infection and drug resistance Discussion HIV V179D;V179D;V179T;V179T 9;99;9;99 16;106;16;106 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Another survey focusing on Burmese individuals staying in Dehong reported that M184V, K103N/KN, and T74S/ST were the major SDRMs associated with VF. 2020 Infection and drug resistance Discussion HIV K103K;K103N;M184V;T74S;T74T 86;86;79;100;100 94;93;84;106;107 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. E138A confers low-level resistance to rilpivirine (RPV) and is more likely a consequence of HIV-1 natural polymorphism. 2020 Infection and drug resistance Discussion HIV E138A 0 5 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Furthermore, we found that the major NNRTI-related SDRMs were K101P, K103N, V106A, E138A, Y181C, and Y188H, and the major NRTI-related SDRMs were L74V/I and M184V. 2020 Infection and drug resistance Discussion HIV E138A;K101P;K103N;L74I;L74V;M184V;V106A;Y181C;Y188H 83;62;69;146;146;157;76;90;101 88;67;74;152;152;162;81;95;106 NNRTI;NRTI 37;122 42;126 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. Some SDRMs, including NRTI-related mutations (M41L, D67E/G/N, K70E/R, M184V, T215any, and K219any) and NNRTI-related mutations (K101E/P, K103N/S, V106A/M, Y181any, G190any, and P225H) were reported in Myanmar. 2020 Infection and drug resistance Discussion HIV D67E;D67G;D67N;K101E;K101P;K103N;K103S;K70E;K70R;M184V;M41L;P225H;V106A;V106M 52;52;52;128;128;137;137;62;62;70;46;177;146;146 60;60;60;135;135;144;144;68;68;75;50;182;153;153 NNRTI;NRTI 103;22 108;26 32368103 HIV-1 Drug Resistance in ART-Naive Individuals in Myanmar. The NNRTI mutation V179D/T was very common in the China-Myanmar border region and appeared in half of the transmission clusters formed by HIV-1 drug-resistance strains in this region. 2020 Infection and drug resistance Discussion HIV V179D;V179T 19;19 26;26 NNRTI 4 9 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. A combination of RT V179D and K103R found in two samples with HIV-1 infection may synergistically reduce EFV and NVP susceptibility about 10-fold, RT mutations with combination of V179D and K103R were also observed in treatment-naive individuals in China. 2020 Scientific reports Discussion HIV K103R;K103R;V179D;V179D 30;190;20;180 35;195;25;185 RT;RT 17;147 19;149 HIV infections 62 77 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Drug resistance analysis demonstrated that 2.4% of HIV-1 isolates contained at least one NNRTI (K101E, K103N) or PI (M46I) SDRMs, the overall prevalence of TDR was lower than previous reports in Zhejiang (11.1%) and Shijiazhuang (6.1%) among treatment-naive HIV-infected individuals, but similar to a nationwide cross-sectional survey about prevalence of TDR (3.6%) in 2015 in China. 2020 Scientific reports Discussion HIV K101E;K103N;M46I 96;103;117 101;108;121 NNRTI;PI 89;113 94;115 HIV infections 258 270 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. In contrast, the most common NNRTI DRMs in our study, V179D/E mutations, were observed within a variety of strains, consistent with selective pressure from use of NNRTI in China. 2020 Scientific reports Discussion HIV V179D;V179E 54;54 61;61 NNRTI;NNRTI 29;163 34;168 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. In particular, the Q58E DRM may be more common in CRF07_BC strains, which was also consistent with a recent study. 2020 Scientific reports Discussion HIV Q58E 19 23 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. M46I/L caused PLLR to many INSTIs among HIV-1 positive individuals, while N88S could result in HLR to Atazanavir (ATV) and NFV, LLR to Indinavir (IDV) and Saquinavir (SQV). 2020 Scientific reports Discussion HIV M46L;N88S;M46I 0;74;0 6;78;6 INSTI 27 33 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Notably, Q58E and V179D/E were the most common DRMs to PI and NNRTI respectively in the study, which is consistent with a previous study focused on five blood centers in China. 2020 Scientific reports Discussion HIV Q58E;V179D;V179E 9;18;18 13;25;25 NNRTI;PI 62;55 67;57 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Q58E and other DRMs (M46L/I, N88S) that confer resistance to PIs were present in our study. 2020 Scientific reports Discussion HIV M46I;M46L;N88S;Q58E 21;21;29;0 27;27;33;4 PI 61 64 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. Q58E was identified as the potential low-level resistance (PLLR)-related muation to Nelfinavir (NFV) and low-level resistance (LLR)-related mutation to Tipranavir (TPV). 2020 Scientific reports Discussion HIV Q58E 0 4 32371875 HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naive blood donors in China. The RT K103N mutation found in two strains can reduce EFV and NVP susceptibility by about 20- and 50-fold, respectively. 2020 Scientific reports Discussion HIV K103N 7 12 RT 4 6 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Analysis of the change in trajectory of the mutant systems compared to the wild type suggested less stability and higher fluctuation of the G140S mutant system compared to the WT system. 2020 PloS one Discussion HIV G140S 140 145 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Another simulation study also revealed the binding mode of EVG and RAL to HIV-1 IN and the structural mechanism of drug resistant mutants (G140A and G149A) that affect the 140's loop region spanning residues 140-149. 2020 PloS one Discussion HIV G140A;G149A 139;149 145;154 IN 80 82 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Further interaction analysis was performed to confirm the hypothesis that the G140S mutation could reduce drug binding by extracting structures at different snapshots of the simulation. 2020 PloS one Discussion HIV G140S 78 83 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Furthermore, the total pairwise non-bonded interaction energy was significantly lower for the G140S mutant compared to the WT, suggesting weaker affinity of the drug DTG for HIV-1C IN in the presence of the mutant. 2020 PloS one Discussion HIV G140S 94 99 IN 181 183 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Furthermore, Xue and team found that the cross-resistance mutation E138K/Q148K resulted in a reduction in the chelation ability of oxygen atoms in INSTIs to Mg2+ in the active site of the mutated intasomes resulting in a reduced binding affinity of RAL and EVG to the protein. 2020 PloS one Discussion HIV E138K;Q148K 67;73 72;78 INSTI 147 153 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Future work will include viral fitness assays to determine the effect of mutants E92Q, Y143R and G140S on the HIV-1C virus replication in the presence of DTG. 2020 PloS one Discussion HIV E92Q;G140S;Y143R 81;97;87 85;102;92 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Here, we found that the G140S mutation resulted in the drug moving further away from the binding pocket. 2020 PloS one Discussion HIV G140S 24 29 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. In our case, the 140's loop region is stabilized by the G140S mutation and we assume that could reduce drug binding. 2020 PloS one Discussion HIV G140S 56 61 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. In this study, we selected three known mutations E92Q, G140S and Y143R associated with RAL, EVG and DTG resistance to investigate their effect on the protein structure of HIV-1C IN and DTG drug binding. 2020 PloS one Discussion HIV E92Q;G140S;Y143R 49;55;65 53;60;70 IN 178 180 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. showed the structural impact of mutations Q148H/R and G140S/A on the flexibility of the HIV-1 IN as a mechanism for RAL resistance. 2020 PloS one Discussion HIV G140A;G140S;Q148H;Q148R 54;54;42;42 61;61;49;49 IN 94 96 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Similarly, the binding free energy calculations also showed higher binding energy between the WT HIV-1C IN and DTG and reduced binding for the E92Q, Y143R and G140S mutant systems. 2020 PloS one Discussion HIV E92Q;G140S;Y143R 143;159;149 147;164;154 IN 104 106 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. study with the WT showing higher pair interaction energy compared to the G140S/Q148H double mutant. 2020 PloS one Discussion HIV G140S;Q148H 73;79 78;84 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. that showed no difference in binding affinity of RAL to the WT and G140S single mutant. 2020 PloS one Discussion HIV G140S 67 72 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. Their results showed that the single G140S mutation did not adversely affect drug binding. 2020 PloS one Discussion HIV G140S 37 42 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. This is supported by pairwise distance analysis confirming a larger distance between the MG ion and drug DTG for the G140S mutant system compared to the WT and Y143R. 2020 PloS one Discussion HIV G140S;Y143R 117;160 122;165 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. We also confirmed the destabilizing effect of the G140S mutant using principal component analysis which suggested larger randomized concerted movement for the G140S mutant compared to the WT, E92Q and Y143R systems. 2020 PloS one Discussion HIV E92Q;G140S;G140S;Y143R 192;50;159;201 196;55;164;206 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. We also observed weaker interactions for the E92Q mutation but stronger interactions for Y143R mutant based on the average number of hydrogen bonds and the total number of polar contacts between the protein and the drug. 2020 PloS one Discussion HIV E92Q;Y143R 45;89 49;94 32379830 Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding. who performed 150 ns simulation studies of the G140S HIV-1B IN mutant system with NAMD and discovered that the 140's loop of the single G140S mutant system displayed reduced movements using principal component analysis. 2020 PloS one Discussion HIV G140S;G140S 47;136 52;141 IN 60 62 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Among the detected NRTI resistance mutations, K65R is a key mutation that causes intermediate/high-level resistance to TDF, DDI, ABC and d4T and low/intermediate resistance to 3TC and FTC. 2020 Epidemiology and infection Discussion HIV K65R 46 50 NRTI 19 23 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. Among the NNRTI resistance mutations in this study, the key mutations were K103N, Y188L and G190A, which usually cause high-level resistance to NNRTIs but whose frequencies were low among the participants. 2020 Epidemiology and infection Discussion HIV G190A;K103N;Y188L 92;75;82 97;80;87 NNRTI;NNRTI 10;144 15;150 32381145 The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China. E138A/G/R results in low-level resistance to RPV and E138K results in intermediate-level resistance to RPV. 2020 Epidemiology and infection Discussion HIV E138A;E138G;E138K;E138R 0;0;53;0 9;9;58;9 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. A Q563R change represents a similar dramatic change in the properties of the amino acid at this position. 2020 PLoS pathogens Discussion HIV Q563R 2 7 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Consistent with this model, we show that the Q563R change results in better virus neutralization by the rare and potent MPER bNAbs (Fig 6). 2020 PLoS pathogens Discussion HIV Q563R 45 50 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. demonstrated that the L669S change dramatically increased binding and neutralization by MPER bNAbs 2F5 and 4E10, suggesting that this change enhances exposure of 2F5 and 4E10 epitopes. 2020 PLoS pathogens Discussion HIV L669S 22 27 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Furthermore, we propose a role for this Q563R substitution in stabilizing Env in conformations that might induce broadly neutralizing MPER-targeted antibodies more effectively. 2020 PLoS pathogens Discussion HIV Q563R 40 45 Env 74 77 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. In our study, the NE1 Q563R virus was found to be 10-fold less infectious than the E1 virus containing the Q563R change, implying that in addition to the role of gp41 antibodies in rescuing the infectivity defect, the primary Env E1 likely contains other changes that have a compensatory effect. 2020 PLoS pathogens Discussion HIV Q563R 107 112 gp41;Env 162;226 166;229 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. In summary, we demonstrate that a naturally occurring Q563R substitution in HIV-1 gp41 leads to a viral infectivity defect by inhibiting six-helix bundle formation and viral entry. 2020 PLoS pathogens Discussion HIV Q563R 54 59 gp41 82 86 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Indeed, Env E1 is divergent from Env NE1 at residues 605, 621 and 648 in gp41 (S4 Fig), which may serve to help restore some of the Q563R-mediated defects. 2020 PLoS pathogens Discussion HIV Q563R 132 137 gp41;Env;Env 73;8;33 77;11;36 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Naturally occurring Q563R variants are rare but have been found in infected individuals. 2020 PLoS pathogens Discussion HIV Q563R 20 25 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Notably, monoclonal antibodies 240D, 246D and F240 that alleviate the Q563R-mediated fusion defect bind a specific epitope within the disulfide loop in gp41. 2020 PLoS pathogens Discussion HIV Q563R 70 75 gp41 152 156 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Our autologous neutralization assays rescuing the Q563R-determined viral defect highlight the approach of testing naturally occurring viral variants in the presence of autologous plasma, to accurately understand in vivo viral activity. 2020 PLoS pathogens Discussion HIV Q563R 50 55 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Our study demonstrates, we believe for the first time, a mechanism whereby a viral defect is alleviated by the host's humoral immune response, specifically the Q563R-determined impaired infectivity of E1 viruses being restored in the presence of anti-HR1 antibodies. 2020 PLoS pathogens Discussion HIV Q563R 160 165 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Since the increased infection is seen specifically with Envs harboring a Q563R mutation, we conclude that these antibodies act to restore a viral defect rather than functioning by generally enhancing infection (Figs 5 and S6). 2020 PLoS pathogens Discussion HIV Q563R 73 78 Env 56 60 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. The effect of a Q563R arginine substitution has been studied by engineering this mutation into NL4.3, HXB2 and YU2 laboratory strains, but efforts to study the viral entry of naturally occurring Q563R variants has been unsuccessful. 2020 PLoS pathogens Discussion HIV Q563R;Q563R 16;195 21;200 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. The Q563R change may thus stabilize Env in a pre-hairpin intermediate conformation, which is the target of the potent and broad MPER antibodies 2F5, 10E8, 7H6 and 4E10. 2020 PLoS pathogens Discussion HIV Q563R 4 9 Env 36 39 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. The rescue of the Q563R variant by both relatively early (2 ypi) and late (6.5 ypi) autologous plasma, as well as by heterologous plasma from multiple individuals, corroborates findings that these gp41-specific antibodies develop early in HIV-1 infection. 2020 PLoS pathogens Discussion HIV Q563R 18 23 gp41 197 201 HIV infections 239 254 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. This Q563R change has previously been shown to reduce infectivity to undetectable levels, making it impossible to study in vitro. 2020 PLoS pathogens Discussion HIV Q563R 5 10 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Through the use of heat-inactivated plasma and FcR blockers, we have shown that the Q563R-specific increase in infection is not due to complement or FcR-mediated enhancement. 2020 PLoS pathogens Discussion HIV Q563R 84 89 32392227 Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein. Viruses with a Q563R change in gp41 have been particularly difficult to study due to their low infectivity. 2020 PLoS pathogens Discussion HIV Q563R 15 20 gp41 31 35 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). Additional support for this hypothesis comes from two retrospective cohort studies in which a historical plasma genotype detecting the M184V mutation was not predictive of virologic failure in participants switching to lamivudine- based dual therapies with either a protease inhibitor or an integrase inhibitor. 2020 EBioMedicine Discussion HIV M184V 135 140 IN;PR 291;266 300;274 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). Another study reported lower viral rebound in persons harboring the M184V who received lamivudine monotherapy compared to patients interrupting treatment. 2020 EBioMedicine Discussion HIV M184V 68 73 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). dual therapy with either boosted protease inhibitor or integrase inhibitor plus lamivudine in persons with past M184V demonstrated only a statistically higher risk of virological failure for those with a viral suppression equal or under three years, which is inferior to the median viral suppression duration in our study. 2020 EBioMedicine Discussion HIV M184V 112 117 IN;PR 55;33 64;41 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). In addition to the antiviral effect of lamivudine, the maintenance of the M184V/I mutations might contribute to the success of dolutegravir plus lamivudine by sustaining a diminished viral fitness and preventing the emergence of resistance mutations against dolutegravir. 2020 EBioMedicine Discussion HIV M184I;M184V 74;74 81;81 32408111 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). The residual antiviral efficacy of lamivudine was demonstrated more than a decade ago in a study showing a viral load increase of 0 5 log10 after discontinuing lamivudine despite the presence of the M184V mutation. 2020 EBioMedicine Discussion HIV M184V 199 204 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. Alone, pre-existing T97A has no or minimal effect on RAL susceptibility, but in combination with other primary mutations in the integrase gene, it reduces susceptibility to RAL and other InSTIs. 2020 Antiviral chemistry & chemotherapy Discussion HIV T97A 20 24 IN;INSTI 128;187 137;193 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. At 48 weeks of treatment, T97A mutation could not be detected in the HIV-1 sequences, possibly due to the selection of variants with higher fitness by RAL or NRTIs included in the regimen, as previously described, resulting in detection missing due to the low sensitivity of Sanger bulk sequencing that is known to detect only variants with prevalence of more than 20%. 2020 Antiviral chemistry & chemotherapy Discussion HIV T97A 26 30 NRTI 158 163 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. G118R, Y143C, and N155H were the main pathways to virologic failure. 2020 Antiviral chemistry & chemotherapy Discussion HIV N155H;Y143C;G118R 18;7;0 23;12;5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. G118R, Y143C, and N155H were the major integrase mutations accounting for the virologic failure detected in three out of seven patients, following 32 to 48 weeks of RAL-based regimen. 2020 Antiviral chemistry & chemotherapy Discussion HIV N155H;Y143C;G118R 18;7;0 23;12;5 IN 39 48 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. M184V mutation in the reverse transcriptase conferring high level resistance to 3TC and FTC accompanied the major integrase mutations. 2020 Antiviral chemistry & chemotherapy Discussion HIV M184V 0 5 RT;IN 22;114 43;123 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. N155H was the main mutation pathway for virologic failure, followed by Q143R and Q148R/H mutation pathways. 2020 Antiviral chemistry & chemotherapy Discussion HIV Q143R;Q148H;Q148R;N155H 71;81;81;0 76;88;88;5 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. T97A mutation occurs in 1% to 4% of viruses from ART-naive patients depending on subtype. 2020 Antiviral chemistry & chemotherapy Discussion HIV T97A 0 4 32434393 Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. The polymorphic mutation, T97A, was detected at baseline in two patients, and disappeared later after starting the RAL-based regimen when only M184V mutation emerged. 2020 Antiviral chemistry & chemotherapy Discussion HIV M184V;T97A 143;26 148;30 32434561 Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. Among the 12 patients with K103N and/or V106M mutations (leading to a functional dual NRTI-therapy), only four were alive and on ART at the end of follow-up. 2020 AIDS research and therapy Discussion HIV K103N;V106M 27;40 32;45 NRTI 86 90 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Dependence of MxB sensitivity on CA conformation, rather than on cofactor binding, was also supported by the demonstration that mutants which mimic the conformational and dynamic changes caused by CypA recruitment to CA (CA A92E and G94D) make HIV-1 R9 sensitive to MxB independently of CypA binding (Figure 3). 2020 eLife Discussion HIV A92E;G94D 224;233 228;237 Capsid;Capsid;Capsid 33;217;221 35;219;223 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Direct recruitment of wild type CA, and not CA N74D, by MxB is the simplest explanation for these data. 2020 eLife Discussion HIV N74D 47 51 Capsid;Capsid 32;44 34;46 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Furthermore, HIV-1 bearing the CPSF6 binding mutant N74D was MxB insensitive, but CPSF6 depletion, which has a similar effect on HIV-1 as N74D mutation in terms of cofactor dependence and integration targeting, did not render HIV-1 R9 GFP MxB insensitive. 2020 eLife Discussion HIV N74D;N74D 52;138 56;142 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Indeed, we observe that, despite insensitivity to MxB mediated inhibition of infectivity, proviral DNA levels of HIV-1 bearing CA P90A were increased by MxB induction (Figure 3B). 2020 eLife Discussion HIV P90A 130 134 Capsid 127 129 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. Mutation N74D replaces the amide side chain with a negatively charged acidic side chain in close spatial proximity to the positively charged K70 (Figure 6:figure supplement 1). 2020 eLife Discussion HIV N74D 9 13 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. This hypothesis is consistent with MxB insensitive HIV-1 CA mutant P90A being reported to retain MxB binding capacity. 2020 eLife Discussion HIV P90A 67 71 Capsid 57 59 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. This suggests that MxB still influences HIV-1 CA P90A, possibly at the level of nuclear entry and integration, despite not reducing the number of GFP positive cells. 2020 eLife Discussion HIV P90A 49 53 Capsid 46 48 32553106 MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. We therefore hypothesise that N74D conformationally alters this region of the capsid to prevent both CPSF6 and MxB binding. 2020 eLife Discussion HIV N74D 30 34 Capsid 78 84 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. In addition, the M184V resistance mutation selected for by ABC, FTC or 3TC imparts a clinical benefit due to reduced viral fitness, increased RT fidelity, and hypersensitization to other NRTIs among others. 2020 PloS one Discussion HIV M184V 17 22 NRTI;RT 187;142 192;144 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. K103N, V106M) drug resistance mutations, typically observed in patients failing an NNRTI-based regimen. 2020 PloS one Discussion HIV V106M;K103N 7;0 12;5 NNRTI 83 88 32555643 HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. Secondly, only a limited number of TDF-treated patients were included in this study and in light of the high prevalence of the K65R mutation in sub-Saharan African countries, it is unclear whether our conclusions are applicable to patients re-suppressing or failing TDF-based regimens in this setting. 2020 PloS one Discussion HIV K65R 127 131 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Also, we observed in p7/p1 the mutations K436R and I437V, both of which have been associated with PI exposure in vivo and in vitro and PI resistance in the absence of protease drug resistance mutations. 2020 The Journal of antimicrobial chemotherapy Discussion HIV I437V;K436R 51;41 56;46 PR;PI;PI 167;98;135 175;100;137 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. However, future site-directed mutagenesis and phenotypic analyses are needed to clarify the specific contributions of K95R and R286K to viral replication and darunavir susceptibility. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K95R;R286K 118;127 122;132 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. In addition, at NCS locations we found changes mainly in p17 (E12K, R76K and T81A), p2 (V370 A/M) and p7 (I389T) previously associated with resistance to PIs. 2020 The Journal of antimicrobial chemotherapy Discussion HIV E12K;I389T;R76K;T81A;V370A 62;106;68;77;88 66;111;72;81;96 NC;PI 16;154 18;157 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. In addition, we detected a small cluster of sequences from PT3 at T2 with mutations I54V and V82A in the protease, which have previously been associated with the loss of viral fitness. 2020 The Journal of antimicrobial chemotherapy Discussion HIV I54V;V82A 84;93 88;97 PR 105 113 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Moreover, in p1/p6 we identified S451N, which has been previously associated with PI exposure in non-B clade HIV-1 subtypes. 2020 The Journal of antimicrobial chemotherapy Discussion HIV S451N 33 38 Gag;PI 16;82 18;84 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Moreover, we identified two signature mutations (K95R in p17 and R286K in p24) in Gag NCS that were enriched in boosted PI-treated subjects during VF according to VESPA analyses. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K95R;R286K 49;65 54;70 p24;Gag;NC;PI 74;82;86;120 77;85;88;122 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. S373P has been associated with a weaker virological response to saquinavir/ritonavir and A374S/P and T375A have been found at increased frequency in PI-experienced individuals. 2020 The Journal of antimicrobial chemotherapy Discussion HIV A374P;A374S;T375A;S373P 89;89;101;0 96;96;106;5 PI 149 151 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. Signature mutations (K95R and R286K) in Gag may be crucial for the development of VF to boosted PIs. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K95R;R286K 21;30 26;35 Gag;PI 40;96 43;99 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. The E12K/D mutation has been previously detected in vitro during selection experiments with amprenavir in the presence of additional PI resistance mutations. 2020 The Journal of antimicrobial chemotherapy Discussion HIV E12D;E12K 4;4 10;10 PI 133 135 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. The identification of K95R and R286K should be further confirmed in a larger number of sequences, but it could potentially help to classify patients with VF to boosted PI. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K95R;R286K 22;31 26;36 PI 168 170 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. The R286K mutation has been recently described as an emerging mutation in two patients infected with the HIV-1 recombinant CRF02_AG during VF to darunavir. 2020 The Journal of antimicrobial chemotherapy Discussion HIV R286K 4 9 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. The R76K mutation has been previously associated with changes in viral fitness and susceptibility to PIs but always in the context of highly resistant HIV-1 proteases. 2020 The Journal of antimicrobial chemotherapy Discussion HIV R76K 4 8 PR;PI 157;101 166;104 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. This model suggests an increase in protein flexibility mediated by K95R and R286K signature Gag mutations. 2020 The Journal of antimicrobial chemotherapy Discussion HIV K95R;R286K 67;76 71;81 Gag 92 95 32556165 HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy. We observed mutations in p2/p7 (S373P, A374S/P and T375A). 2020 The Journal of antimicrobial chemotherapy Discussion HIV A374P;A374S;S373P;T375A 39;39;32;51 46;46;37;56 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. and elvitegravir (EVG), respectively, compared to virus lacking S230R. 2020 Medicine Discussion HIV S230R 64 69 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. Common INSTI RAMS include R263K, Q148H/R/K, G118R, G140A/S/C, E138A/K/T, N155H, and Y143C/R. 2020 Medicine Discussion HIV E138A;E138K;E138T;G118R;G140A;G140C;G140S;N155H;Q148H;Q148K;Q148R;R263K;Y143C;Y143R 62;62;62;44;51;51;51;73;33;33;33;26;84;84 71;71;71;49;60;60;60;78;42;42;42;31;91;91 INSTI 7 12 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. Pham et al, using an infectious molecular clone with the insertion of S230R by site-directed mutagenesis, showed that this mutation conferred a 63% reduction of integrase enzyme efficiency and a fold change in mean IC50 of 3.85, 3.72, 1.52, and 1.21 for DTG, cabotegravir, raltegravir. 2020 Medicine Discussion HIV S230R 70 75 IN 161 170 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. The S230R mutation has been previously described in 2 individuals failing DTG monotherapy in the DOMONO study. 2020 Medicine Discussion HIV S230R 4 9 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. These results demonstrated that the S230R substitution caused similar effects on viral replicative capacity as R263K, which is known to be selected in vitro by EVG, DTG, and BIC causing viral resistance on an incompletely suppressive DTG containing regimen. 2020 Medicine Discussion HIV R263K;S230R 111;36 116;41 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. This lack of detectable phenotypic resistance may have been reflective of the low copy number of virus carrying the S230R mutation (167 copies/mL). 2020 Medicine Discussion HIV S230R 116 121 32629687 Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naive individual case report. We were unable to obtain partner's virus for analysis to determine if they also had the S230R mutation as well. 2020 Medicine Discussion HIV S230R 88 93 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Consistently, compound 13 retained full potency of inhibition against the NNRTI drug-resistant HIV-1 strain K103N-Y181C. 2020 Viruses Discussion HIV K103N;Y181C 108;114 113;119 NNRTI 74 79 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. Similar to RDS1759, compound 13 shows interactions with residues Asn474 and Gln475 involved in the RNase H primer grip motif but, besides, it also interacts with Gly444, Arg448, Glu449 and Arg557 amino acid residues, some of them previously investigated and shown to be involved in the binding of RNase H active-site inhibitors.To prove compound 13 binding mode and its most critical interactions with RT, site-directed mutagenesis experiments were conducted, generating RTs carrying R448A, Q475A or R557A amino acid substitutions. 2020 Viruses Discussion HIV Q475A;R448A;R557A 491;484;500 496;489;505 RT;RT 402;471 404;474 32640577 Targeting HIV-1 RNase H: N'-(2-Hydroxy-benzylidene)-3,4,5-Trihydroxybenzoylhydrazone as Selective Inhibitor Active against NNRTIs-Resistant Variants. The significant loss of potency of compound 13 against all the generated mutant RTs proved the critical role of those amino acid residues for its binding to the RNase H domain and implies a binding orientation different from RDS1759, imidazolidinedione derivatives and beta-thujaplicinol that were reported to be fully active against both R448A and R557A HIV-1 RTs. 2020 Viruses Discussion HIV R448A;R557A 339;349 344;354 RT;RT 80;361 83;364 32675772 Brief Report: Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and SWORD-2 Randomized Clinical Trials. Interestingly, in 1 participant with baseline integrase substitutions N155N/H and G163G/R by proviral DNA genotype assay, only the integrase polymorphism mixture (V151V/I), which is not associated with dolutegravir resistance, was detected at virologic failure. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G163G;G163R;N155H;N155N;V151I;V151V 82;82;70;70;163;163 89;89;77;77;170;170 IN;IN 46;131 55;140 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. However, TDF in the presence of 3TC has been shown to induce M184V mutation which enhances the efficacy of 3TC-TDF combination. 2020 PloS one Discussion HIV M184V 61 66 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. In combination, M41L plus T215Y confer intermediate / high-level resistance to Zidovudine (AZT) and Stavudine (d4T) and contribute to reduced Didanosine (ddI), Abacavir (ABC) and Tenofovir (TDF) susceptibility. 2020 PloS one Discussion HIV M41L;T215Y 16;26 20;31 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K103N and M230L conferred high level resistance to the first-line NNRTIs. 2020 PloS one Discussion HIV M230L;K103N 10;0 15;5 NNRTI 66 72 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K238T, V179E, M230L and E138A found in the participants in the urban setting conferred resistance to NNRTIs. 2020 PloS one Discussion HIV E138A;M230L;V179E;K238T 24;14;7;0 29;19;12;5 NNRTI 101 107 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. K65R causes intermediate/high-level resistance to TDF, ddI, ABC and d4T and low/intermediate resistance to Lamivudine (3TC) and Emtricitabine (FTC) but has also been found to increase susceptibility to AZT. 2020 PloS one Discussion HIV K65R 0 4 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. Of note the mutation K65R was found in one naive patient. 2020 PloS one Discussion HIV K65R 21 25 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. The emergence of K65R in naive patients in our study strongly suggest reduced efficacy of first line regimens, hence the need for proper surveillance of this mutation among this population. 2020 PloS one Discussion HIV K65R 17 21 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. The most common mutation to NRTIs found in our study was M41L (13.33%, 2/15). 2020 PloS one Discussion HIV M41L 57 61 NRTI 28 33 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. The mutation E138A found both in rural and urban setting confers low-level resistance to second generation NNRTIs and their presence alone or in conjunction with the mutation M138I causes decreased susceptibility of the virus to ETV and RPV. 2020 PloS one Discussion HIV E138A;M138I 13;175 18;180 NNRTI 107 113 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. The mutation M184V which on its own confers high level resistance to 3TC and FTC (about 100-fold increase) was detected amongst these patients. 2020 PloS one Discussion HIV M184V 13 18 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. The mutation M41L is a TAM that usually occurs with T215Y. 2020 PloS one Discussion HIV M41L;T215Y 13;52 17;57 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. The mutation Y188YH (quasi-specie) found only in the rural setting renders an intermediate level of resistance to the first-line NNRTIs. 2020 PloS one Discussion HIV Y188H;Y188Y 13;13 19;19 NNRTI 129 135 32692778 Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon. The mutations k103N, E138G, P225H. 2020 PloS one Discussion HIV E138G;P225H 21;28 26;33 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. Also, the M184V mutation occurs more frequently with dual ART use rather than triple therapy. 2020 BMC infectious diseases Discussion HIV M184V 10 15 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. dominant wild type virus at month one) suggest that resistance developed as a result of PrEP use, as one would expect that M184V would be a major population from the outset if it was a transmitted virus. 2020 BMC infectious diseases Discussion HIV M184V 123 128 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. K65R which we see in the later time points. 2020 BMC infectious diseases Discussion HIV K65R 0 4 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. PrEP-selected resistance (M184V mutation) is strongly selected by FTC and 3TC and emerges rapidly in patients receiving either of these drugs. 2020 BMC infectious diseases Discussion HIV M184V 26 32 32698772 Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa. The M184V mutation virus strain adversely affects viral replicative capacity and is less fit compared to the wild type strain, hence it is less likely to be transmitted during infection. 2020 BMC infectious diseases Discussion HIV M184V 4 9 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. In a similar study, E138A was found in ART-naive pregnant women attending antenatal care in a teaching hospital in Accra, Ghana. 2020 Virology journal Discussion HIV E138A 20 25 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. The accessory and minor mutations found were F77L and L10F in RT gene and PR gene respectively. 2020 Virology journal Discussion HIV F77L;L10F 45;54 49;58 PR;RT 74;62 76;64 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. The E138A mutation is a polymorphic mutation that occurs in an appreciable number of drug-naive patients such as the population studied and confers resistance to etravirine (ETR) and rilpivirine (RPV), which are NNRTIs. 2020 Virology journal Discussion HIV E138A 4 9 NNRTI 212 218 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. The K65R mutation is found to reduce viral susceptibility to most NRTIs by approximately 2-fold and rather increase susceptibility to AZT and hence reduced viral replication with zidovudine-containing therapy. 2020 Virology journal Discussion HIV K65R 4 8 NRTI 66 71 32709248 Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana. Two (2) major DRMs were found in two (2) samples sequenced in the RT gene (E138A and K65R) and none in the PR gene. 2020 Virology journal Discussion HIV E138A;K65R 75;85 81;89 PR;RT 107;66 109;68 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. A lower genetic barrier for L74I mutations in sub-subtype A6 can lead to quicker development of drug resistance than subtype B, which is especially important in light of virological failures in patients with the L74I mutation from Russia in the ATLAS and FLAIR studies. 2020 Viruses Discussion HIV L74I;L74I 28;212 32;216 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Additionally, for position 74, we showed a lower genetic barrier for L74M and L74I mutations in sub-subtype A6. 2020 Viruses Discussion HIV L74I;L74M 78;69 82;73 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Five of them (R20K, I72V, L74I, S119P, and V201I) were described as INSTI resistant. 2020 Viruses Discussion HIV I72V;L74I;R20K;S119P;V201I 20;26;14;32;43 24;30;18;37;48 INSTI 68 73 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. In a large number of sequences of subtype A, we also showed that subtype B differs from subtype A at positions 140 and 151, and subtype B had a lower genetic barrier to the occurrence of mutations G140C and V151I, which could play a role in INSTI resistance. 2020 Viruses Discussion HIV G140C;V151I 197;207 202;212 INSTI 241 246 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Remarkably, the prevalence of 12 polymorphic mutations (K14R, R20K, L74I, S119P, T124S, T124A, V126F, G134N, T218I, L234I, S255N, and S283G) was significantly different between sub-subtypes A6 and A1. 2020 Viruses Discussion HIV G134N;K14R;L234I;L74I;R20K;S119P;S255N;S283G;T124A;T124S;T218I;V126F 102;56;116;68;62;74;123;134;88;81;109;95 107;60;121;72;66;79;128;139;93;86;114;100 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The origin and dispersal of L74I are identical, and the tMRCA of L74I was estimated in 1998, which is in accordance with the previously estimated dates of the A6 epidemic among the injectors. 2020 Viruses Discussion HIV L74I;L74I 28;65 32;69 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. The potential contribution of naturally occurring polymorphisms, particularly the L74I mutation, in HIV-1 integrase to the evolution of resistance under the selective pressure of INSTIs may have clinical and virological implications. 2020 Viruses Discussion HIV L74I 82 86 IN;INSTI 106;179 115;185 32752001 Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs. Therefore, we estimated the temporal origin and phylogenetic characteristics of the sub-subtype A6 viruses with the L74I mutation and showed that viruses with L74I spread as a result of a founder effect among IDUs across FSU countries, validating our initial hypothesis. 2020 Viruses Discussion HIV L74I;L74I 116;159 120;163 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Given our data suggesting the H196Q variant can arise in vivo in SIVmac239 infected macaques as a result of escape from CTL responses, these data may suggest that SIVmac251 was isolated from an animal that targeted this region with CTL, leading to viral escape, and prior to other escape variants becoming dominant, as happened in our previous study. 2020 PloS one Discussion HIV H196Q 30 35 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Here, we show that E191R at least partially restores the ability to downregulate CD4, which is also lost with the H196Q variant suggesting that E191R does more than just enhance interaction with tetherin. 2020 PloS one Discussion HIV E191R;E191R;H196Q 19;144;114 24;149;119 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Here, we show that evolution of the E191R variant restored tetherin downregulation in the presence of Q196. 2020 PloS one Discussion HIV E191R 36 41 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. However, our previous report showed that the H196Q variant disrupted multiple Nef functions that rely on AP-2 interactions suggesting that disruption of a direct interaction with tetherin likely does not fully explain the functional deficits identified in this variant. 2020 PloS one Discussion HIV H196Q 45 50 Nef 78 81 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. One of the Nef variants with the greatest impact on tetherin downregulation was the H196Q variant. 2020 PloS one Discussion HIV H196Q 84 89 Nef 11 14 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. Taken together, our mutational and functional data combined with published structural and sequence data suggest the possibility that the E191R variant in SIVmac might enhance an interaction between Nef and tetherin thus restoring the ability of Nef to downregulate tetherin in the presence of the H196Q variant, but that this variant may not restore all functions that are impacted by the H196Q variant. 2020 PloS one Discussion HIV E191R;H196Q;H196Q 137;297;389 142;302;394 Nef;Nef 198;245 201;248 32764749 Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant. These structures show that H196 does not directly interact with host AP-2 but is predicted to form a salt bridge with tetherin, which is predicted to be disrupted in the H196Q variant using PISA software. 2020 PloS one Discussion HIV H196Q 170 175 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. In terms of HIVDR to NRTI, the prevalence of any TAMs was at 32.8% and the most common TAM's were K70R/T/Q/N/E (32.8%), K219Q/E (22.4%), D67N (17.2%), T215IT (15.5%) and M41L (5.2%). 2020 PloS one Discussion HIV D67N;K219E;K219Q;K70E;K70N;K70Q;K70R;K70T;M41L;T215I;T215T 137;120;120;98;98;98;98;98;170;151;151 141;127;127;110;110;110;110;110;174;157;157 NRTI 21 25 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The high prevalence of individual TAMs (D67N and K70R) or TAMs in combination (M41L with T215Y) reduces susceptibility to Zidovudine (a key drug for most second line regimens). 2020 PloS one Discussion HIV D67N;K70R;M41L;T215Y 40;49;79;89 45;53;84;94 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The high prevalence of the Y181C and Y188C mutations has been demonstrated in earlier studies from the region including Zambia. 2020 PloS one Discussion HIV Y181C;Y188C 27;37 32;42 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The TAMs of K70R/T/Q/N/E, K219Q/E, and D67N in combination effectively reduce the potency of zidovudine in a second line combination. 2020 PloS one Discussion HIV D67N;K219E;K219Q;K70E;K70N;K70Q;K70R;K70T 39;26;26;12;12;12;12;12 43;33;33;24;24;24;24;24 32804970 Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia. The third major finding of this study was the high prevalence of the Y188CE (36.2%) and Y181C (36.2%) mutations, indicating resistance to third line therapy etravirine and rilpivirine, to which none of our study participants had ever been exposed to. 2020 PloS one Discussion HIV Y181C;Y188C;Y188E 88;69;69 93;75;75 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. A significantly decreased transactivation was observed when we used pseudovirions containing the Y44A and Y55A Tat mutations, compared to the wild-type protein. 2020 International journal of molecular sciences Discussion HIV Y44A;Y55A 97;106 101;110 Tat 111 114 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Based on stability analyses, Y44A was assumed to inactivate HIV-2 Tat, as we predicted a destabilizing nature of the mutation by multiple methods. 2020 International journal of molecular sciences Discussion HIV Y44A 29 33 Tat 66 69 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. For comparison, Y55A Tat mutant was also studied. 2020 International journal of molecular sciences Discussion HIV Y55A 16 20 Tat 21 24 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Furthermore, Western blot of the pseudovirion lysate revealed that RT was not detectable in the presence of Y44A mutation. 2020 International journal of molecular sciences Discussion HIV Y44A 108 112 RT 67 69 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Here, we have characterized the Y44A mutation in HIV-2 Tat protein, and evaluated its effect on RT activity, and facilitation of proviral transcription in an indicator cell line. 2020 International journal of molecular sciences Discussion HIV Y44A 32 36 Tat;RT 55;96 58;98 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Nevertheless, our finding regarding the Y44A mutant confirms that mutation at the 44th residue also diminishes the activity of Tat. 2020 International journal of molecular sciences Discussion HIV Y44A 40 44 Tat 127 130 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. Our results showed that Y44A mutation of Tat completely abolished RT activity, compared to the wild-type, akin to the Y55A mutation. 2020 International journal of molecular sciences Discussion HIV Y44A;Y55A 24;118 28;122 Tat;RT 41;66 44;68 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The possible mechanism behind the proposed stabilization of RT by Tat remains to be elucidated, and perhaps our results indicate degradation of the RT as a result of the Y44A Tat mutation. 2020 International journal of molecular sciences Discussion HIV Y44A 170 174 Tat;Tat;RT;RT 66;175;60;148 69;178;62;150 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. The Y44A mutation was predicted to alter the structure of an ordered region, thereby inactivating the protein. 2020 International journal of molecular sciences Discussion HIV Y44A 4 8 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. This was expected for the Y55A mutant, since Y26A mutation of HIV-1 Tat has been proved to reduce Tat-induced activation of HIV LTR, and Y55 residue of HIV-2 Tat corresponds the tyrosine in the 26th position of HIV-1 Tat. 2020 International journal of molecular sciences Discussion HIV Y26A;Y55A 45;26 49;30 LTR;Tat;Tat;Tat;Tat 128;68;98;158;217 131;71;101;161;220 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. We carried out experiments on HIV indicator cell line to assess the effect of the Y44A and Y55A Tat mutations on transactivation of the proviral genome. 2020 International journal of molecular sciences Discussion HIV Y44A;Y55A 82;91 86;95 Tat 96 99 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. We hypothesized that the mutation might have interfered with the stability and packaging of the RT into the pseudovirions as others have described previously, therefore, we carried out transfection experiments using plasmids coding for the wild-type and Y44A Tat mutant, and utilized Western blot analysis of cell lysate to detect changes in RT during a 3 day period. 2020 International journal of molecular sciences Discussion HIV Y44A 254 258 Tat;RT;RT 259;96;342 262;98;344 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. We then carried out a series of in vitro experiments to study the inactivating nature of the Y44A mutation and characterize its effect on reverse transcription and viral replication. 2020 International journal of molecular sciences Discussion HIV Y44A 93 97 RT 138 159 32824587 Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation. While expression of the RT was clearly detectable in the case of the wild-type in all studied time points, in relatively equal amounts, we noticed that in the presence of Y44A Tat mutant, the amount of RT was significantly lower in the first day after transfection, and was almost undetectable on day 3 post-transfection (Figure 6b). 2020 International journal of molecular sciences Discussion HIV Y44A 171 175 Tat;RT;RT 176;24;202 179;26;204 32843050 First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens. Specifically, previous exposure to RAL (a drug with a low-genetic barrier to resistance) in a context of poor adherence contributed to selecting mutations (E138KQ, G140A, Q148R) conferring cross-resistance to DTG. 2020 Antimicrobial resistance and infection control Discussion HIV E138K;E138Q;G140A;Q148R 156;156;164;171 162;162;169;176 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. ART expansion in Indonesia may be related with the high prevalence of K103N and Y181C, because NVP and EFV are used in the firstline ART regimens in this country. 2020 Infectious disease reports Discussion HIV K103N;Y181C 70;80 75;85 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. Detection of K103N as a TDR was consistent to the finding of the same mutation as the most frequent NNRTI-related drug resistance mutation found in Surabaya, Indonesia. 2020 Infectious disease reports Discussion HIV K103N 13 18 NNRTI 100 105 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. In the present study, no TDR against PIs was detected, while minor mutations, M36I (85.71%), H69K (85.71%), L89M (76.19%), K20R (57.14%), and G16E (47.62%), were frequently detected among 85.71% of PR genes (Table 1). 2020 Infectious disease reports Discussion HIV G16E;H69K;K20R;L89M;M36I 142;93;123;108;78 146;97;127;112;82 PI;PR 37;198 40;200 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. Low TDR prevalence (3,6%; <5%), the presence of K103N, and high prevalence of CRF01_AE in China were reported by Zhao et al. 2020 Infectious disease reports Discussion HIV K103N 48 53 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. On the contrary, higher TDR prevalence was found in European countries and the United States; however, higher rate of K103N mutation was observed among Indonesian individuals recently infected with HIV-1. 2020 Infectious disease reports Discussion HIV K103N 118 123 32874468 Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia. Samples from SS21 and SS41 contained K103N and Y181C mutations that conferred viral resistance against EFV and NVP. 2020 Infectious disease reports Discussion HIV K103N;Y181C 37;47 42;52 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. A key result is showing that a single amino acid substitution at position 16 (M16E) endows SIVcpzPtt Vif with gA3G degradation activity. 2020 PLoS pathogens Discussion HIV M16E 78 82 Vif 101 104 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Although the M16E substitution enabled SIVcpzPtt Vif to neutralize gA3G efficiently, the reverse substitution in SIVgor Vif. 2020 PLoS pathogens Discussion HIV M16E 13 17 Vif;Vif 49;120 52;123 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. Collectively, our findings suggest that the acquisition of M16E mutation in Vif was a major step for SIVcpz to neutralize gA3G, but some additional mutations, which can fortify and/or compensate the ability of SIVgor Vif to degrade gA3G, may be needed during the adaptation to gorilla. 2020 PLoS pathogens Discussion HIV M16E 59 63 Vif;Vif 76;217 79;220 32913367 A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. E16M) did not cause a loss in counteraction. 2020 PLoS pathogens Discussion HIV E16M 0 4 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. First and foremost, in vitro studies show that, in contrast to V106A or V106M, V106I does not confer a potency reduction to DOR. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106A;V106I;V106M 63;79;72 68;84;77 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. In addition, the presence of RT V106I does not seem to enhance the replicative capacity of viruses isolated from participants with PDVF (Table 4). 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106I 32 37 RT 29 31 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. In this NNRTI-experienced population (N = 6893), intermediate-level (defined as detection of any RT V106A/M, Y188C/H, V108I, and K103N + P225H substitution) and high-level (defined as detection of any RT Y188L, M230L, G190E, V106A/M + F227L, and V106A/M + L234I substitutions) DOR resistance was seen in 12.7% and 6.1%, respectively, and the most common high-level DOR resistance-associated substitution was RT Y188L. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227L;G190E;K103N;L234I;M230L;P225H;V106A;V106A;V106A;V106M;V106M;V106M;V108I;Y188C;Y188H;Y188L;Y188L 235;218;129;256;211;137;100;225;246;100;225;246;118;109;109;204;411 240;223;134;261;216;142;107;232;253;107;232;253;123;116;116;209;416 NNRTI;RT;RT;RT 8;97;201;408 13;99;203;410 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. It is highly unlikely that the RT V106I substitution confers a higher level of resistance to the PI (darunavir) than the NNRTI (DOR). 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106I 34 39 NNRTI;PI;RT 121;97;31 126;99;33 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Moreover, in a resistance analysis among participants with HIV-1 RT V106I viruses at baseline across 3 phase 2/3 DOR clinical trials in treatment-naive participants infected with subtype B virus and treated in combination with 2 NRTIs for 48 weeks, 7 (87.5%) of 8 participants treated with DOR, compared with 4 (57.1%) of 7 participants treated with darunavir, achieved HIV-1 RNA <50 copies/mL. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106I 68 73 NRTI;RT 229;65 234;67 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Nonetheless, available data suggest that RT V106I is a polymorphism rather than a resistance-associated substitution selected by DOR. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106I 44 49 RT 41 43 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Some participants in the DRIVE-SHIFT trial of a virologically suppressed population, and all participants in the DRIVE-BEYOND trial of treatment-naive participants, had baseline mutations, including the RT K103N, Y181C, and/or G190A substitutions. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G190A;K103N;Y181C 227;206;213 232;211;218 RT 203 205 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. The most prevalent DOR resistance-associated substitutions detected among participants with PDVF in DOR clinical trials were substitutions at RT positions 106 (V106A/I/M) and 227 (F227C). 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C;V106A;V106I;V106M 180;160;160;160 185;169;169;169 RT 142 144 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. The RT V106I substitution emerged in 3 participants compared with 1 participant each for V106A and V106M, often in combination with F227C. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C;V106A;V106I;V106M 132;89;7;99 137;94;12;104 RT 4 6 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. There were no treatment-emergent RT K103N, G190A, or Y181C substitutions in any DOR clinical trial; this is in contrast with the EFV group in DRIVE-AHEAD in which 10 of 12 isolates tested exhibited a RT K103N substitution, and the other 2 had an RT G190E substitution. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G190A;G190E;K103N;K103N;Y181C 43;249;36;203;53 48;254;41;208;58 RT;RT;RT 33;200;246 35;202;248 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. This is consistent with in vitro resistance selection studies in which V106A/M preceded emergence of F227C/L/V in RT in most cases. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C;F227L;F227V;V106A;V106M 101;101;101;71;71 110;110;110;78;78 RT 114 116 32925358 Review of Doravirine Resistance Patterns Identified in Participants During Clinical Development. Thus, the totality of the data suggests that RT V106I is a polymorphism and not a DOR resistance-associated substitution. 2020 Journal of acquired immune deficiency syndromes (1999) Discussion HIV V106I 48 53 RT 45 47 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. M184V associates with high-level resistance to abacavir, emtricitabine, and lamivudine; while K70R and D67N are among the TAMs. 2020 PloS one Discussion HIV D67N;K70R;M184V 103;94;0 107;98;5 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. The most frequent NNRTI resistance-associated mutations were K103N, V106M, and G190A that confer high-level resistance to efavirenz and nevirapine. 2020 PloS one Discussion HIV G190A;K103N;V106M 79;61;68 84;66;73 NNRTI 18 23 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. This study further reports frequent NRTI resistance-associated mutations as M184V, K70R, and D67N in line with other studies. 2020 PloS one Discussion HIV D67N;K70R;M184V 93;83;76 97;87;81 NRTI 36 40 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. This study reports co-existence of T69D mutation with at least one TAM in three samples. 2020 PloS one Discussion HIV T69D 35 39 32986709 Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania. Two of these samples had M41L and T215Y TAMs, a combination which further enhances cross-resistance to all US FDA approved NRTIs, a phenomenon known as Multi-NRTI resistance. 2020 PloS one Discussion HIV M41L;T215Y 25;34 29;39 NRTI;NRTI 123;158 128;162 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. E138A mutation, which is associated with a decreased response to ETR and RPV according to the IAS-USA mutation list, was found in 3.9% (2/51) of the specimens showing a similar frequency of detection in previous reports from Ethiopia. 2020 Retrovirology Discussion HIV E138A 0 5 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. In agreement with our report, K101E, K103N, and E138A mutations of the RT region had been reported previously in Ethiopia among ART-naive individuals. 2020 Retrovirology Discussion HIV E138A;K101E;K103N 48;30;37 53;35;42 RT 71 73 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. On the other hand, V106A (Mutation in the RT region that confers resistance to NNRTIs), M114V and Y115F (Mutations in the RTs region that confer resistance to NRTIs) and G73S (Mutation in the PI region that confers resistance to PIs) were all detected for the first time. 2020 Retrovirology Discussion HIV G73S;M114V;V106A;Y115F 170;88;19;98 174;93;24;103 NNRTI;NRTI;PI;PI;RT;RT 79;159;192;229;42;122 85;164;194;232;44;125 32993693 Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia. The most frequent minor mutations observed in the PR sequence were H69K (100%) and M36L (98%), followed by L89M (58.8%), I15V (25.5%), K20R (25.5%), and T74S (17.6%). 2020 Retrovirology Discussion HIV H69K;I15V;K20R;L89M;M36L;T74S 67;121;135;107;83;153 71;125;139;111;87;157 PR 50 52 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Finally, Sahloff and colleagues retrospectively evaluated the use of boosted DRV plus TDF/FTC in 32 treatment-experienced patients with at least an M184V/I mutation. 2020 SAGE open medicine Discussion HIV M184I;M184V 148;148 155;155 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Of note, the patients in this trial had only the M184V/I mutation, unlike the population in our study which often had multiple resistance-conferring mutations present. 2020 SAGE open medicine Discussion HIV M184I;M184V 49;49 56;56 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Perez-Valero and colleagues prospectively evaluated switching to a single tablet regimen containing two active agents (EVG, cobicistat, FTC, and TAF) in 34 virologically suppressed patients with the M184V/I mutation. 2020 SAGE open medicine Discussion HIV M184I;M184V 199;199 206;206 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. retrospectively evaluated switching to dual therapy with 3TC plus either bPI or INSTI in 436 patients, 87 (20%) of which had the M184V mutation. 2020 SAGE open medicine Discussion HIV M184V 129 134 INSTI 80 85 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. retrospectively examined switching to a regimen containing ABC, 3TC, and DTG in treatment-experienced patients and found that the M184V mutation, present in 137 patients (8.4% of study population), was not associated with increased risk of virologic failure. 2020 SAGE open medicine Discussion HIV M184V 130 135 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. Similar rates of viral suppression were found regardless of the number of active ARVs in this study of treatment-experienced patients with HIV and at minimum an M184V/I mutation. 2020 SAGE open medicine Discussion HIV M184I;M184V 161;161 168;168 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The DOLULAM study, a single arm, prospective cohort of 27 treatment-experienced, virologically suppressed patients, 17 (63%) of which had a documented M184V mutation, found that switching to DTG and 3TC maintained viral suppression in 100% of patients at 2 years. 2020 SAGE open medicine Discussion HIV M184V 151 156 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The presence of the M184V mutation was, however, associated with higher probability of experiencing viral blips. 2020 SAGE open medicine Discussion HIV M184V 20 25 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The results of our study lend support to the growing body of evidence that patients with the M184V/I mutation may maintain viral suppression in the setting of less than three fully active agents. 2020 SAGE open medicine Discussion HIV M184I;M184V 93;93 100;100 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. The use of less than three active agents in patients with the M184V/I mutation has not been evaluated in large, prospective studies. 2020 SAGE open medicine Discussion HIV M184I;M184V 62;62 69;69 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. There are several reasons why a patient may not be prescribed an NRTI, including adverse events and resistance; however, there are potential benefits of maintaining selection pressure for the M184V/I mutation. 2020 SAGE open medicine Discussion HIV M184I;M184V 192;192 199;199 NRTI 65 69 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. There is little evidence regarding optimal NRTI-sparing regimens in patients with the M184V/I mutation. 2020 SAGE open medicine Discussion HIV M184I;M184V 86;86 93;93 NRTI 43 47 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. These studies, in congruence with the results of our study, suggest that regimens containing <3 active agents and continuing 3TC or FTC may maintain acceptable viral suppression in the setting of an M184V/I mutation. 2020 SAGE open medicine Discussion HIV M184I;M184V 199;199 206;206 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. They found that the M184V mutation was not associated with increased risk of virologic failure or treatment discontinuation at a median follow-up of 1.3 years compared with patients with at least one non-M184V mutation. 2020 SAGE open medicine Discussion HIV M184V;M184V 20;204 25;209 33014372 Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen. This is likely reflective of the fact that the most convincing prospective data available in treatment-experienced patients, 85% with an M184V/I mutation and 26% with 3-class resistance, utilized an NRTI-containing three active agent regimens. 2020 SAGE open medicine Discussion HIV M184I;M184V 137;137 144;144 NRTI 199 203 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. A longitudinal analysis of one individual infected with the Pol S653K virus showed that SL9-1K-specific T cells selected Pol S653L and S653T mutant viruses. 2021 AIDS (London, England) Discussion HIV S653K;S653L;S653T 64;125;135 69;130;140 Pol;Pol 60;121 63;124 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. A similar mechanism was reported based on the study of the subtype B virus-infected Japanese individuals having a detrimental allele HLA-B*35:01, which study showed that the Nef Y135F mutation selected by HLA-A*24:02-restricted T cells impaired the TCR recognition and viral suppression ability of YF9-specific T cells restricted by HLA-B*35:01. 2021 AIDS (London, England) Discussion HIV Y135F 178 183 Nef 174 177 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. In addition, 1K/1Q-specific T cells effectively recognized cells infected with Pol S653K/Q viruses. 2021 AIDS (London, England) Discussion HIV S653K;S653Q 83;83 90;90 Pol 79 82 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. In the current study, we demonstrated that the accumulation of Pol S653A/T/L mutations within the HLA-C*15:05-restricted Pol SL9 epitope led to a poor clinical outcome in 74 HIV-1 subtype A/E-infected Vietnamese individuals having HLA-C*15:05. 2021 AIDS (London, England) Discussion HIV S653A;S653L;S653T 67;67;67 76;76;76 Pol;Pol 63;121 66;124 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. Since Pol S653K and Pol S653Q mutations are not associated with any HLA alleles, it is difficult to clarify the origin of these mutants. 2021 AIDS (London, England) Discussion HIV S653K;S653Q 10;24 15;29 Pol;Pol 6;20 9;23 33031103 Critical effect of Pol escape mutations associated with detrimental allele HLA-C*15: 05 on clinical outcome in HIV-1 subtype A/E infection. We detected T-cell responses to SL9-1K and SL9-1Q mutant epitopes in approximately 45% of individuals infected with Pol S653K/Q viruses. 2021 AIDS (London, England) Discussion HIV S653K;S653Q 120;120 127;127 Pol 116 119 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. Although there is discordance in these mutations between the CSF and plasma, according to the Stanford HIV drug resistance database, M46MI only confers resistance PI only when present with other mutation while I84T is not known to produce resistance to PI. 2020 Medicine Discussion HIV I84T;M46I;M46M 210;133;133 214;138;138 PI;PI 163;253 165;255 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. In 1 participant, NNRTI mutations K101E and V106 M were observed in plasma and CSF compartment, respectively. 2020 Medicine Discussion HIV K101E;V106M 34;44 39;50 NNRTI 18 23 33031315 Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana. One participant had M46MI mutation and the other had I84IT. 2020 Medicine Discussion HIV I84I;I84T;M46I;M46M 53;53;20;20 58;58;25;25 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. Importantly, the antiviral state established in response to HIV-1 CA P90A treatment required TRIM5 and the autophagy factors BECN1 and ULK1 (Figs 6 and 7). 2020 PLoS pathogens Discussion HIV P90A 69 73 Capsid 66 68 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. The P90A capsid mutation is only different from the WT by a single amino acid substitution, yet this change dramatically impacts the virus' susceptibility to TRIM5 CSR and its ability to prime STR. 2020 PLoS pathogens Discussion HIV P90A 4 8 Capsid 9 15 33052966 A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha. We found that the signaling induced by HIV-1 CA P90A infection could potently inhibit the ability of otherwise TRIM5-resistant HIV-1 and Sendai virus to infect THP-1 macrophages. 2020 PLoS pathogens Discussion HIV P90A 48 52 Capsid 45 47 HIV infections 39 62 33101270 The Signature Amino Acid Residue Serine 31 of HIV-1C Tat Potentiates an Activated Phenotype in Endothelial Cells. It would be necessary to understand if the natural variation of C31S in HIV-1C Tat, leading to significantly enhanced induction of CCL2 production, is a compensatory mechanism for the differences in the basic domain and the RGD motif. 2020 Frontiers in immunology Discussion HIV C31S 64 68 Tat 79 82 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Interestingly, we observed that the cytoplasmic domain of some Vpu variants shows substitution of phosphorylated serine residues (S52I, S56I, and S61P). 2020 BioResearch open access Discussion HIV S52I;S56I;S61P 130;136;146 134;140;150 Vpu 63 66 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. It is noteworthy that when compared with the S61A mutation, S61P Vpu mutants displayed enhanced intracellular expression and kinetic stability. 2020 BioResearch open access Discussion HIV S61A;S61P 45;60 49;64 Vpu 65 68 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Results of CHX chase assay confirmed a higher kinetic stability associated with S61P mutants. 2020 BioResearch open access Discussion HIV S61P 80 84 33117613 Genetic and Functional Characterization of HIV-1 Vpu from HIV-1-Infected North Indian Population. Substitution of serine residue (S61A) in HIV-1 pNL4-3 Vpu was reported earlier to enhance viral replication and stability of Vpu protein. 2020 BioResearch open access Discussion HIV S61A 32 36 Vpu;Vpu 54;125 57;128 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. A549 cells were infected with MCPyV 7 P sample, in which Ser251Phe was detected in concomitant with the substitution Asp69Val and Tyr79 . 2020 International journal of molecular sciences Discussion HIV D69V;S251F 117;57 125;66 Asp 117 120 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Although the Thr47Ser substitution is sited in the VP1 N-terminus region, this mutation did not compromise the NLS sequence and did not prevent the transfer of VP1 from the cytoplasm to the nucleus. 2020 International journal of molecular sciences Discussion HIV T47S 13 21 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Both servers found that the variant Ile115Phe, sited near to the two beta-sheets, into the beta-sandwich region, did not affect the conformation, but stabilizes the protein structure. 2020 International journal of molecular sciences Discussion HIV I115F 36 45 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Except for the Ile115Phe substitution, all the variations detected in this study are involved in epitopes recognized by B cells. 2020 International journal of molecular sciences Discussion HIV I115F 15 24 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Ile115Phe, found into the beta-sandwich region, near to the two beta-sheets, could prejudice the stability of the beta-sandwich core and subsequently the whole VP1 protein. 2020 International journal of molecular sciences Discussion HIV I115F 0 9 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. In addition to the Ser251Phe change within the first neutralizing epitope loop in the MCPyV 7 P sample, the substitutions Asp69Val and the Tyr79 were observed. 2020 International journal of molecular sciences Discussion HIV D69V;S251F 122;19 130;28 Asp 122 125 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. In vitro replication experiments revealed that A549 cells infected with 7 U sample, carrying MCPyV VP1 characterized by Thr47Ser mutation, supported MCPyV replication less well than A549 cells infected with MCPyV prototype DNA (MCC350 strain) and containing virions. 2020 International journal of molecular sciences Discussion HIV T47S 120 128 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Mutation of D60N (that corresponds with D69 in MCPyV VP1) in combination with K69N, A72V and E82Q in BKPyV VP1 reduced BKPyV infectivity in HEK293TT cells 5-fold compared to BKPyV with wild-type VP1. 2020 International journal of molecular sciences Discussion HIV A72V;D60N;E82Q;K69N 84;12;93;78 88;16;97;82 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. None of the nucleotide mutations detected in our MCPyV VP1 DNA sequences have been reported before and, consequently, also the amino-acid mutations had never been reported previously, except for the Ser251Phe change, described by Baez and colleagues. 2020 International journal of molecular sciences Discussion HIV S251F 199 208 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Only one mutation, the Thr47Ser, was found sited in the VP1 N-terminus region. 2020 International journal of molecular sciences Discussion HIV T47S 23 31 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. The D60N mutation in BKPyV VP1 disrupts the epitope bound by the neutralizing monoclonal 41F17, but the effect of the single D60N mutation on BKPyV infectivity was not tested. 2020 International journal of molecular sciences Discussion HIV D60N;D60N 4;125 8;129 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. The DynaMut server analysis suggests that the mutation Thr47Ser reduces protein stability. 2020 International journal of molecular sciences Discussion HIV T47S 55 63 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. The Ile115Phe substitution in MCPyV VP1 of sample 17U, sited in the VP1 beta-sandwich core, is located in the corresponding CD-loop of SV40 VP1 and is part of the consensus sequence ED(L)(I)(M)T found in VP1 of SV40, BKPyV, JCPyV, TSPyV, HPyV10, HPyV12, and LiPyV. 2020 International journal of molecular sciences Discussion HIV I115F 4 13 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. The substitution Ser251Phe occurred in the apical or membrane-binding loop, considered responsible for virus-cell interaction. 2020 International journal of molecular sciences Discussion HIV S251F 17 26 33121182 Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. The trend of the MCPyV load in A549 cells infected with virions characterized by Ile115Phe was essentially the same observed in cells infected with MCPyV prototype DNA (control), confirming that this mutation is not involved in attachment of the virus to host cell receptors, virus entry or in its replicative capabilities. 2020 International journal of molecular sciences Discussion HIV I115F 81 90 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. As expected, she rapidly acquired K101E, K103N and V106M mutations. 2020 Infection and drug resistance Discussion HIV K101E;K103N;V106M 34;41;51 39;46;56 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Consequently, we compared the sensitivity of In-house SBS and NGS methods to detect minority variants of HIV-1 DRM, and a minor V106M mutation with a frequency of 4.30% was found by NGS method in patient M but not identified by SBS, which is associated with high-level reductions in NVP and EFV susceptibility. 2020 Infection and drug resistance Discussion HIV V106M 128 133 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. In this case, patient F was infected with the V106I mutant of HIV-1 according to phylogenetic tree analysis and developed to chronic infection status without knowing it. 2020 Infection and drug resistance Discussion HIV V106I 46 51 HIV infections 125 142 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. Patient M performed genotypic resistance mutation testing two months after the cessation of ART, when the circulating viruses may have changed, so the mutants frequency of K101E and K103N were 41.03% and 27.56%, respectively. 2020 Infection and drug resistance Discussion HIV K101E;K103N 172;182 177;187 33122923 Transmitted and Acquired HIV-1 Drug Resistance from a Family: A Case Study. The common V106I mutant of three patients, transmitted through sexual transmission and mother-to-child transmission, respectively, is also a strong evidence of how DRM spreads in HIV-1 naive individuals. 2020 Infection and drug resistance Discussion HIV V106I 11 16 33143751 Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria. Interestingly, a significantly higher rate of K65R mutation was observed among patients infected predominantly with CRF02_AG (16.7% of K65R) and G (12.0%) HIV-1 strains on first-line ART in this West African setting. 2020 AIDS research and therapy Discussion HIV K65R;K65R 46;135 50;139 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Although our present study implicates G123E in reduced PI susceptibility, we show here that the combination of mutations that was observed in the patient was needed for maximal effect. 2020 mBio Discussion HIV G123E 38 43 PI 55 57 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. G123E was reported to arise when viruses were propagated with investigational protease inhibitors KNI-272 and UIC-94003. 2020 mBio Discussion HIV G123E 0 5 PR 78 86 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Gag G123E was found to potentially interact with protease by NMR, providing a potential mechanism for its effect. 2020 mBio Discussion HIV G123E 4 9 PR;Gag 49;0 57;3 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. Given the change in the overall size and charge of the residue in the WT and mutants (from small and neutral to large and acidic), the G123E mutation alters the accessibility and electrostatic properties in the vicinity of the cleavage site and therefore was expected to directly interfere with proteolysis. 2020 mBio Discussion HIV G123E 135 140 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. We aimed to understand the mechanism at play in the T122A/G123E/S126del/H127del phenotype. 2020 mBio Discussion HIV G123E;T122A 58;52 63;57 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. We were able to detect both T122A and G123 at low abundance at baseline, prior to PI exposure. 2020 mBio Discussion HIV T122A 28 33 PI 82 84 33144375 In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. When this deletion occurred alongside T122A and G123E, we observed a 4- to 5-fold decrease in susceptibility to lopinavir. 2020 mBio Discussion HIV G123E;T122A 48;38 53;43 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Further detailed studies are needed to clarify the effects of the Y120F and Q125H mutations on Nef functions of different subtype backbones. 2020 Scientific reports Discussion HIV Q125H;Y120F 76;66 81;71 Nef 95 98 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. In addition, D123A mutant impairs Nef's ability to counteract SERINC3/5 as shown in this study. 2020 Scientific reports Discussion HIV D123A 13 18 Nef 34 37 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. In our study, the immune-escape mutations, Y120F, Q125H, and the double mutations (Y120F/Q125H), exhibited the prevalence of 39.2, 13.1, and 9.3%, respectively; in this study cohort in Japan, the values are much higher than those of subtype B sequences in Los Alamos Database, which are 13.6, 5.2, and 1.6%, respectively. 2020 Scientific reports Discussion HIV Y120F;Q125H;Q125H;Y120F 83;89;50;43 88;94;55;48 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. Indeed, D123N mutation prevents Nef core dimer formation when bound to Hck SH3 of Src-family kinases. 2020 Scientific reports Discussion HIV D123N 8 13 Nef 32 35 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. It is thus interesting to see whether and to what extent the immune-escape mutations at the neighboring residues of Y120F and Q125H play a secondary role in Nef dimerization. 2020 Scientific reports Discussion HIV Q125H;Y120F 126;116 131;121 Nef 157 160 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. The highly conserved D123 residue (> 99% prevalence in subtype A, B, C and D) is encompassed by the immune-escape mutation sites of Y120F and Q125H. 2020 Scientific reports Discussion HIV Q125H;Y120F 142;132 147;137 33173092 Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. We have demonstrated here that a number of naturally-occurring Nef variants (Y120F and Q125H) associated with a certain HLA class I allele (HLA-B*51:01) inversely correlated with the plasma viral load in treatment-naive HIV-infected patients harboring this HLA allele. 2020 Scientific reports Discussion HIV Q125H;Y120F 87;77 92;83 Nef 63 66 HIV infections 220 232 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. A recent European observational study assessed the impact of the M184V/I mutation on the virological failure rate on the DTG/3TC/ABC regimen. 2020 Viruses Discussion HIV M184I;M184V 65;65 72;72 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Furthermore, TAF exhibits still full efficacy in the presence of the M184V/I mutation in contrast to ABC. 2020 Viruses Discussion HIV M184I;M184V 69;69 76;76 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Given that TDF/TAF still exhibits full efficacy in the presence of the M184V/I mutation, this backbone component should be preferred in combination with DTG in low:and middle-income countries. 2020 Viruses Discussion HIV M184I;M184V 71;71 78;78 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. In this setting, pre-existing NRTI-associated mutations:including the M184V/I mutation:are highly prevalent and there is no possibility of close viral load monitoring. 2020 Viruses Discussion HIV M184I;M184V 70;70 77;77 NRTI 30 34 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. It is convincing that in our case the combination of poor adherence with low-level replication and pre-existing M184V/I mutation, first observed as a low-abundant variant in the SSITT study, led to virological failure and consecutively emergence of INSTI resistance. 2020 Viruses Discussion HIV M184I;M184V 112;112 119;119 INSTI 249 254 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Of the 1626 patients included, 137 (8.4%) harbored the genotypically documented M184V/I mutation. 2020 Viruses Discussion HIV M184I;M184V 80;80 87;87 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Other INSTIs with a lower resistance barrier than DTG, such as elvitegravir (EVG) in the co-formulation EVG/cobicistat/FTC/TAF, showed to be effective in maintaining viral suppression despite archived M184V/I mutations at week 24 in a prospective open-label study. 2020 Viruses Discussion HIV M184I;M184V 201;201 208;208 INSTI 6 12 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Overall, the study observed a very low virological failure rate (1.3%) after the switch to ABC/3TC/DTG, with no statistically significant difference in the virological failure incidence among patients with or without M184V/I. 2020 Viruses Discussion HIV M184I;M184V 217;217 224;224 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Patients with the M184V/I mutation had a lower CD4 nadir and a long history of antiviral treatment. 2020 Viruses Discussion HIV M184I;M184V 18;18 25;25 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Therefore, we cannot exclude that the M184I mutation detected at different time points may potentially be linked to different viral quasispecies. 2020 Viruses Discussion HIV M184I 38 43 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. Thirdly, the patient harbored the M184V/I mutation, which causes reduced susceptibility to two (3TC, ABC) out of the three components of the DTG/3TC/ABC regimen. 2020 Viruses Discussion HIV M184I;M184V 34;34 41;41 33228206 Emergence of Resistance to Integrase Strand Transfer Inhibitors during Dolutegravir Containing Triple-Therapy in a Treatment-Experienced Patient with Pre-Existing M184V/I Mutation. This is a rare case of a patient with pre-existing M184V/I mutation and virological failure on a DTG/3TC/ABC regimen with the emergence of INSTI resistance mutations. 2020 Viruses Discussion HIV M184I;M184V 51;51 58;58 INSTI 139 144 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. In the current study, the frequency mutation associated with drug-resistance to NRTI was M184V 10.5%, which is the major mutation observed in most of the previous studies. 2020 Medicine Discussion HIV M184V 89 94 NRTI 80 84 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The E138A, conferring resistance to Rilpivirine, and Etravirine, V179VD confers resistance to Efavirenz, Etravirine, Nevirapine, and Rilpivirine, while V106I confers resistance to Etravirine, Nevirapine, Rilpivirine, and Doravirine. 2020 Medicine Discussion HIV E138A;V106I;V179D;V179V 4;152;65;65 9;157;71;71 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The most frequent mutations detected in this study were V82A + I84IV which are associated with PI conferring resistance to Atazanavir, Lopinavir, Lamivudine, Emtricitabine, Darunavir, and Abacavir. 2020 Medicine Discussion HIV I84I;I84V;V82A 63;63;56 68;68;60 PI 95 97 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The mutations associated with NNRTI resistance were V179VD, V106I, and E138A. 2020 Medicine Discussion HIV E138A;V106I;V179D;V179V 71;60;52;52 76;65;58;58 NNRTI 30 35 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The mutations associated with resistance to PI were V82A + I84IV 1.8%, and L10F + Q58E 1.8%. 2020 Medicine Discussion HIV I84I;I84V;L10F;Q58E;V82A 59;59;75;82;52 64;64;79;86;56 PI 44 46 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The only mutation associated with NRTI resistance was M184 V, which confers resistance to Atazanavir, Lopinavir, Lamivudine, Emtricitabine, Darunavir, and Abacavir. 2020 Medicine Discussion HIV M184V 54 60 NRTI 34 38 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. The other mutations associated with PI were L10F + Q58E which confer resistance to Atazanavir, Lopinavir, Lamivudine, Emtricitabine, Darunavir, and Abacavir. 2020 Medicine Discussion HIV L10F;Q58E 44;51 48;55 PI 36 38 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. These results are inconsistent with the previous study of Jamjoom et al, who reported that the most prevalent PI mutations were I54 V, L90 M, V82A, M46I, I50 V, and D30N. 2020 Medicine Discussion HIV D30N;I50V;I54V;L90M;M46I;V82A 165;154;128;135;148;142 169;159;133;140;152;146 PI 110 112 33285702 Genotyping and antiretroviral drug resistance of human immunodeficiency Virus-1 in Jazan, Saudi Arabia. While the mutations associated with resistance to NNRTI were V179DV (1.8%), V106I (1.8%), and E138A (1.8%). 2020 Medicine Discussion HIV E138A;V106I;V179D;V179V 94;76;61;61 99;81;67;67 NNRTI 50 55 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. Also, sufficient participants could not be enrolled to meet the target sample size, given the specific inclusion criteria (many PLWH with M184V/I have co-occurring mutations and/or virologic failure, making them ineligible). 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 138;138 145;145 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. Although all participants in this study, had a historical plasma genotypic report of M184V/I, archived M184V/I was detected in only 43.8% of participants at baseline. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184I;M184V;M184V 85;103;85;103 92;110;92;110 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. However, all participants met the primary end point, regardless of whether M184V/I was detected in their baseline proviral DNA genotype. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 75;75 82;82 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. However, exclusion of other NRTI resistance mutations meant that our findings are attributable to M184V/I mutation, alone or in combination with 1-2 TAMs. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 98;98 105;105 NRTI 28 32 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. In summary, M184V/I resistance mutation does not jeopardize the efficacy of a treatment change to E/C/F/TAF, with high rates of virologic suppression maintained throughout 48 weeks of treatment. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 12;12 19;19 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. In this study, 100% virologic suppression was maintained in participants with virologic suppression at baseline and with a historical genotypic report of M184V/I resistance (alone or with 1-2 TAMs), who switched to E/C/F/TAF from a stable antiretroviral regimen. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 154;154 161;161 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. The efficacy of the FTC-containing regimen may reflect partial antiviral activity of FTC despite the resistance conferred by M184V, rather like the beneficial effect of combining 3TC with boosted PI therapy for PLWH despite M184V mutation. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V;M184V 125;224 130;229 PI 196 198 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. The hypersensitivity of viruses with M184V to tenofovir and the high level of intracellular TFV-DP associated with TAF also likely contributed to the observed high efficacy. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 37 42 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. The primary end point was achieved by all participants in parts 1 and 2, suggesting that efficacy was similar for participants with or without TAMs in addition to M184V/I. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 163;163 170;170 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. These findings support E/C/F/TAF fixed-dose combination as a treatment option for virologically suppressed individuals with HIV and M184V/I mutation. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 132;132 139;139 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. Using E/C/F/TAF gives assurance that those harboring hidden M184V/I mutations can remain suppressed. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 60;60 67;67 33315694 Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. Using PBMC-HIV DNA testing to determine whether a participant has M184V/I mutation before choosing a switch regimen can be helpful if the test shows the mutation but might not detect existent mutations in all participants. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 66;66 73;73 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. G163R (0.24%, 2/827) confers low-level resistance to EVG and RAL. 2020 Infection and drug resistance Discussion HIV G163R 0 5 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. G163R was also detected in one patient (0.2%, 1/513) in Yunnan Province. 2020 Infection and drug resistance Discussion HIV G163R 0 5 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. One patient sample contained the T97A mutation, which is a polymorphic INSTI-selected mutation that, depending on subtype, occurs in 1% to 5% of viruses from untreated persons, has minimal effects on INSTI susceptibility but in combination with other major resistance mutations, conferring potential low-level resistance to EVG and RAL. 2020 Infection and drug resistance Discussion HIV T97A 33 37 INSTI;INSTI 71;200 76;205 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. Seven patient samples contained the E157Q mutation, which is a polymorphic mutation that confers potential low-level resistance, and it generally only occurs in combination with other high- or intermediate-level resistance mutations. 2020 Infection and drug resistance Discussion HIV E157Q 36 41 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. Two patient samples contained the A128T mutation, which is a relatively nonpolymorphic possibly INSTI-selected mutation that does not appear to reduce INSTI susceptibility. 2020 Infection and drug resistance Discussion HIV A128T 34 39 INSTI;INSTI 96;151 101;156 33324078 Absence of Integrase Inhibitor-Associated Resistance Among Antiretroviral Therapy-Naive HIV-1-Infected Adults in Guangdong Province, China, in 2018. Two patient samples contained the G163R mutation, which is polymorphic in subtype F viruses from ARV-naive patients but is otherwise non-polymorphic, and confers low-level resistance to elvitegravir (EVG) and RAL. 2020 Infection and drug resistance Discussion HIV G163R 34 39 33324386 Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. For L1, six amino-acid mutations affected two antigenic sites: the BC loop (T84N, Pt422) and the FGb loop (T315N, Pt363, Pt422, Pt574, Pt644, and Pt798; Figure 7, Supplementary Table 1). 2020 Frontiers in microbiology Discussion HIV T315N;T84N 107;76 112;80 33347449 The genotype distribution, infection stage and drug resistance mutation profile of human immunodeficiency virus-1 among the infected blood donors from five Chinese blood centers, 2014-2017. In the study of the same five central blood stations from 2012 to 2014, it was found that V179E was still the main mutation in the current study in NNRTI DRM. 2020 PloS one Discussion HIV V179E 90 95 NNRTI 148 153 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. However, mutations like the RT K103NS, the T215 revertants and the PI L90M appear to have little effect on viral fitness and may persist for prolonged periods in individuals with TDR. 2021 HIV medicine Discussion HIV K103N;K103S;L90M 31;31;70 37;37;74 PI;RT 67;28 69;30 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Of the most frequent NNRTI DRMs, G190ASE occurred predominately as minor variants while K103NS was dominant in the quasispecies. 2021 HIV medicine Discussion HIV G190A;G190E;G190S;K103N;K103S 33;33;33;88;88 40;40;40;94;94 NNRTI 21 26 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. study, a similar pattern was observed, with the M46IL and D30N detected predominately as minor variants while the majority of L90M mutations occurred above the 20% threshold. 2021 HIV medicine Discussion HIV D30N;L90M;M46I;M46L 58;126;48;48 62;130;53;53 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The detection of some DRMs predominately at low levels is likely due to impaired viral fitness, which has been described for mutations such as M184VI and D30N. 2021 HIV medicine Discussion HIV D30N;M184I;M184V 154;143;143 158;149;149 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The M184VI may also be linked with other DRMs and tends to wane over time due to overgrowth of more replication competent wild-type virus. 2021 HIV medicine Discussion HIV M184I;M184V 4;4 10;10 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The most commonly detected NRTI DRMs, K219QENR and M184VI, occurred predominately as minor variants while the majority of patients with T215 revertants had the mutation in > 80% of the quasispecies. 2021 HIV medicine Discussion HIV K219E;K219N;K219Q;K219R;M184I;M184V 38;38;38;38;51;51 46;46;46;46;57;57 NRTI 27 31 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The most commonly detected surveillance INSTI DRMs were G143CHR, associated with high-level resistance to raltegravir, but these were only detected as minor variants. 2021 HIV medicine Discussion HIV G143C;G143H;G143R 56;56;56 63;63;63 INSTI 40 45 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. The only INSTI DRMs detected above the 20% threshold were G140S and G140A, which are associated with intermediate resistance to raltegravir and elvitegravir. 2021 HIV medicine Discussion HIV G140A;G140S 68;58 73;63 INSTI 9 14 33369017 Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study. Within the PI-related DRMs, the same picture emerged, with M46IL and D30N predominately seen as minor variants, whereas L90M (associated with saquinavir resistance), if present, dominated the quasispecies. 2021 HIV medicine Discussion HIV D30N;L90M;M46I;M46L 69;120;59;59 73;124;64;64 PI 11 13 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Atomic-resolution simulations of the mature Gag CA domain showed that the H219Q mutation may play a role in optimizing CypA interactions by controlling the conformational flexibility of the CypA binding loop and fine-tuning the CypA binding affinity. 2021 Computational and structural biotechnology journal Discussion HIV H219Q 74 79 Gag;Capsid 44;48 47;50 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Mutations in the MA domain are concentrated on the predicted membrane binding surface and at least three of them - E12K, E40K and L75R - render the surface more positively charged compared to wild type Gag. 2021 Computational and structural biotechnology journal Discussion HIV E12K;E40K;L75R 115;121;130 119;125;134 Gag;Matrix 202;17 205;19 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. Two clinical mutations, G123E and H219Q, are found in these regions and alter the accessibility and electrostatic properties of the protease binding site. 2021 Computational and structural biotechnology journal Discussion HIV G123E;H219Q 24;34 29;39 PR 132 140 33425260 The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations. We also found that a mutation in the CA domain, Q199H, likely enhances oligomerisation by providing more stabilising interactions between adjacent subunits. 2021 Computational and structural biotechnology journal Discussion HIV Q199H 48 53 Capsid 37 39 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. In this study, however, there was no K22H in patients resistant to antiretroviral drugs, although two of six patients with K22N revealed resistant viruses (HPs 9 and 19). 2021 Journal of ginseng research Discussion HIV K22H;K22N 37;123 41;127 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. It is known that changes such as K22H in Vif protein are associated with the development of resistance to antiretroviral drugs. 2021 Journal of ginseng research Discussion HIV K22H 33 37 Vif 41 44 33437166 The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. RMs to INSTIs and the Q151M complex in 2014 are frequent in KRG-naive patients (22%). 2021 Journal of ginseng research Discussion HIV Q151M 22 27 INSTI 7 13 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. However, doravirine appears to be more efficient than efavirenz and/or rilpivirine in suppressing resistance breakthrough of HIV-1 strains with the common NNRTI resistance-associated mutations such as K103N, Y181C or K103N/Y181C. 2021 Viruses Discussion HIV K103N;K103N;Y181C;Y181C 201;217;208;223 206;222;213;228 NNRTI 155 160 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Impaired PPT processing by the N348I/T369I HIV-1BH10 RT shown in our experiments could be attributed to its inability to locate the G*A site of the PPT/U3 junction at the RNase H active site, when the RT is bound in a polymerase-dependent mode (i.e., with 3' end of the DNA at the polymerase active site). 2021 Viruses Discussion HIV N348I;T369I 31;37 36;42 Pol;Pol;RT;RT 218;281;53;201 228;291;55;203 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. In this scenario connection subdomain mutations N348I/T369I appear to play a critical role by reducing RNase H-mediated cleavage of PPT-containing RNA strands (Figure 3). 2021 Viruses Discussion HIV N348I;T369I 48;54 53;59 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Interestingly, the results shown above reveal that doravirine, the most recently approved NNRTI, stimulates PPT removal to levels similar to those shown by nevirapine, and like in the case of this drug these effects can be suppressed by the combination of N348I and T369I. 2021 Viruses Discussion HIV N348I;T369I 256;266 261;271 NNRTI 90 95 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Molecular dynamics studies have shown that N348I/T369I did not induce any significant structural change, although those mutations modulate conformational dynamics by enhancing the rigidity of the connection subdomain due to the influence of neighboring hydrophobic residues that restrict the mobility of the RNase H domain. 2021 Viruses Discussion HIV N348I;T369I 43;49 48;54 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Our findings demonstrate the dominant effect of both mutations in the presence of NRTI and NNRTI resistance mutations while other polymorphisms found in viruses selected under therapeutic pressure and not tested previously (at positions 399 and 400) had minor effects on the RNase H cleavage patterns obtained with N348I RT. 2021 Viruses Discussion HIV N348I 315 320 NNRTI;NRTI;RT 91;82;321 96;86;323 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Our mutagenesis experiments with HIV-2EHO RT showed negligible effects on RNase H cleavage specificity when substituting residues at the connecting loop (e.g., G344E/D345P/ins346F). 2021 Viruses Discussion HIV D345P;G344E 166;160 171;165 RT 42 44 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. showed that nevirapine enhanced PPT removal during initiation of plus-strand DNA synthesis, while the N348I mutation reverted this effect. 2021 Viruses Discussion HIV N348I 102 107 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The amino acid substitution N348I at the HIV-1 RT connection subdomain has a detrimental effect on RNase H activity while reducing the association rate of RT and nevirapine. 2021 Viruses Discussion HIV N348I 28 33 RT;RT 47;155 49;157 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The dominance of N348I could be reflected in a loss of viral fitness, that could prevent or delay the emergence of drug resistance under certain conditions. 2021 Viruses Discussion HIV N348I 17 22 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The effectiveness of doravirine in suppressing transmitted drug resistance mediated by K103N was crucial for its approval. 2021 Viruses Discussion HIV K103N 87 92 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The highest levels of doravirine resistance (fold-change >100) have been associated with amino acid substitutions V106A/G190A/F227L, E138K/Y181C/M230L and Y188L (alone or in combination with K103N or V106I). 2021 Viruses Discussion HIV E138K;F227L;G190A;M230L;V106A;Y181C;K103N;V106I;Y188L 133;126;120;145;114;139;191;200;155 138;131;125;150;119;144;196;205;160 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The N348I substitution is likely to affect interactions involved in beta-sheet packaging, while side-chains of Glu344 and Lys347 are exposed to the solvent. 2021 Viruses Discussion HIV N348I 4 9 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. The suppressive effects of N348I were found to be stronger in the presence of T369I. 2021 Viruses Discussion HIV N348I;T369I 27;78 32;83 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Therefore, in this context, N348I could also delay the emergence of NNRTI resistance. 2021 Viruses Discussion HIV N348I 28 33 NNRTI 68 73 33477685 Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction. Thus, HIV-1 replication assays revealed that amino acid substitutions N348I or M184V/N348I decreased the replication capacity of viruses carrying E138K in their RT, a mutation that confers resistance to rilpivirine and etravirine. 2021 Viruses Discussion HIV E138K;M184V;N348I;N348I 146;79;70;85 151;84;75;90 RT 161 163 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. Although the prevalence of TDR to PIs (0.44%) was significantly lower than the prevalence of TDR to NNRTIs/NRTIs, the I54M mutation caused universal resistance to PI drugs. 2021 BMC infectious diseases Discussion HIV I54M 118 122 NNRTI;NRTI;PI;PI 100;107;34;163 106;112;37;165 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. Among these mutations, K103N (n = 9) and Y181C/I (n = 7) were the most common TDRMs. 2021 BMC infectious diseases Discussion HIV K103N;Y181C;Y181I 23;41;41 28;48;48 33478415 Increase in HIV-1-transmitted drug resistance among ART-naive youths at the China-Myanmar border during 2009 ~ 2017. In summary, large sample size and more epidemiological data are required to evaluate the potential role of three classes of TDR (NNRTI/NRTI/PI) or K103N, Y181C in affecting the decline of CD4 count. 2021 BMC infectious diseases Discussion HIV K103N;Y181C 147;154 152;159 NNRTI;NRTI;PI 129;135;140 134;139;142 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. (iv) A new hydrogen bond is formed between the side chains of adjacent Arg63 and Ser67 residues on neighbouring MA molecules in the center of the trimer interface of myr(-)MA Q63R, providing the first structural evidence for an additional intermolecular interaction in the trimer interface. 2021 The Journal of biological chemistry Discussion HIV Q63R 175 179 Matrix;Matrix 112;172 114;174 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. (v) SV and SE data show that the A45E, T70R, and Q63R mutations had minimal effect on the monomer-trimer equilibrium, whereas the L75G mutation enhanced the population of the monomeric form by twofold. 2021 The Journal of biological chemistry Discussion HIV A45E;L75G;Q63R;T70R 33;130;49;39 37;134;53;43 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Another interesting result is the finding that S67R behaved like Q63R in its ability to rescue the defect imposed by L13E, indicating that an Arg at either residue 63 or 67 could rescue the L13E defect. 2021 The Journal of biological chemistry Discussion HIV L13E;L13E;Q63R;S67R 117;190;65;47 121;194;69;51 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. As detected by NMR, the largest CSPs were observed for the L75G mutant. 2021 The Journal of biological chemistry Discussion HIV L75G 59 63 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Based on the structure of the myr(-)MA Q63R protein. 2021 The Journal of biological chemistry Discussion HIV Q63R 39 43 Matrix 36 38 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. For viruses with MA L75E mutation, compensatory mutations D14N/V45I, Q28K, V35I/F44L, and E52K were identified. 2021 The Journal of biological chemistry Discussion HIV D14N;E52K;F44L;L75E;Q28K;V35I;V45I 58;90;80;20;69;75;63 62;94;84;24;73;79;67 Matrix 17 19 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. However, the effect was more dramatic in restoring Env incorporation to a WT level when this mutation was introduced along with the Env-defective L13E mutant. 2021 The Journal of biological chemistry Discussion HIV L13E 146 150 Env;Env 51;132 54;135 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. In this study, we have shown that: (i) mutations that either impaired (A45E, T70R, and L75G) or rescued (Q63R) Env incorporation had no adverse effects on the structures and folding of the MA protein. 2021 The Journal of biological chemistry Discussion HIV A45E;L75G;Q63R;T70R 71;87;105;77 75;91;109;81 Env;Matrix 111;189 114;191 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Interestingly, even the L13E/Q63K mutant exhibited a partial rescue, as infectivity in TZM-bl cells was comparable with that of L13E/Q63R, no rescue of Env incorporation was apparent. 2021 The Journal of biological chemistry Discussion HIV L13E;L13E;Q63K;Q63R 24;128;29;133 28;132;33;137 Env 152 155 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. It is worth noting that previous studies indicated that residue Gln63 is not crucial for Env incorporation in the context of otherwise-WT MA and that Q63R is unique for its ability to fully rescue Env incorporation defects. 2021 The Journal of biological chemistry Discussion HIV Q63R 150 154 Env;Env;Matrix 89;197;138 92;200;140 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Our data presented here demonstrate that neither of the three mutants that were proposed to inhibit MA trimerization (A45E, T70R, and L75G) completely shifted the equilibrium to a monomer, nor did the Q63R mutation, which rescues Env incorporation, form a stable trimer in solution even though a new H-bond is observed between the side chains of Arg63 and Ser67 from neighboring subunits. 2021 The Journal of biological chemistry Discussion HIV A45E;L75G;Q63R;T70R 118;134;201;124 122;138;205;128 Env;Matrix 230;100 233;102 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Role of Ser67 and Thr70 in Env incorporation in the context of WT, L13E, Q63R, and L13E/Q63R clones was also investigated. 2021 The Journal of biological chemistry Discussion HIV L13E;L13E;Q63R;Q63R 67;83;73;88 71;87;77;92 Env 27 30 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Substitution of residue Gln63 with Arg suppressed Env incorporation defects of the L13E, E17K, L31E, V35E, and E99V MA mutations. 2021 The Journal of biological chemistry Discussion HIV E17K;E99V;L13E;L31E;Q63R;V35E 89;111;83;95;24;101 93;115;87;99;38;105 Env;Matrix 50;116 53;118 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Taken together, Q63R appears to be unique for its ability to fully rescue Env incorporation defects. 2021 The Journal of biological chemistry Discussion HIV Q63R 16 20 Env 74 77 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The close proximity of Arg63 and Ser67 and their role in the stabilization of the MA trimer are supported by the finding that MA forms dimer and trimer in the glutaraldehyde cross-linking assay conducted with the double mutant (Q63K/S67K) in Jurkat and MT4 cell lines. 2021 The Journal of biological chemistry Discussion HIV Q63K;S67K 228;233 232;237 Matrix;Matrix 82;126 84;128 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The current hypothesis suggests that Q63R mutation may stabilize the trimer structure such that MA lattices, which form large hexamer holes, are favored over those that feature small hexamer holes. 2021 The Journal of biological chemistry Discussion HIV Q63R 37 41 Matrix 96 98 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. The single T70A mutant was also impaired for infectivity and Env incorporation, suggesting that Thr70 may be involved in MA function. 2021 The Journal of biological chemistry Discussion HIV T70A 11 15 Env;Matrix 61;121 64;123 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. This hypothesis was further supported by the finding that the Q63R mutation promoted interaction with gp41CT without altering the organization of MA on a membrane layer. 2021 The Journal of biological chemistry Discussion HIV Q63R 62 66 Matrix 146 148 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Viruses with MA L75G mutation acquired mutations G11S, V35I/F44I, V35I/E52K, V46I, and E52K. 2021 The Journal of biological chemistry Discussion HIV E52K;E52K;F44I;G11S;L75G;V35I;V35I;V46I 71;87;60;49;16;55;66;77 75;91;64;53;20;59;70;81 Matrix 13 15 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. When introduced as a single mutation in MA, Q63R only minimally enhanced Env incorporation. 2021 The Journal of biological chemistry Discussion HIV Q63R 44 48 Env;Matrix 73;40 76;42 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. When the L13E/Q63[E/G/K/L/N/W] double mutants were subjected to the same analysis, none of the Gln63 mutants was able to fully rescue the virus replication, infectivity, and Env incorporation defects imposed by the L13E mutant. 2021 The Journal of biological chemistry Discussion HIV L13E;L13E 9;215 13;219 Env 174 177 33485964 Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation. Whereas the S67A mutation had no effect on the phenotypes of the four viral clones, T70A blocked the ability of Q63R to rescue L13E infectivity and Env incorporation, although Q63R/T70A was as infectious as Q63R alone. 2021 The Journal of biological chemistry Discussion HIV L13E;Q63R;Q63R;Q63R;S67A;T70A;T70A 127;112;176;207;12;84;181 131;116;180;211;16;88;185 Env 148 151 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Addition of IP6 did allow K25R and K25N to form cones, albeit with markedly reduced kinetics and with an increased proportion of larger cones, or tubes in case of K25N. 2021 PLoS pathogens Discussion HIV K25N;K25N;K25R 35;163;26 39;167;30 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Cryo-tomography on purified HIV virions shows that K25A mutants also have a maturation defect; indeed we were unable to find convincing examples of properly mature capsids. 2021 PLoS pathogens Discussion HIV K25A 51 55 Capsid 164 171 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. However, the ability of IP6 to promote the assembly of capsid cones in the absence of high salt was lost in K25A. 2021 PLoS pathogens Discussion HIV K25A 108 112 Capsid 55 61 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. If K25 were only a destabilising force then K25A should more efficiently form pentamers whereas the fact that it assembles tubes but not cones in vitro, suggests that K25 is participating in an interaction that actively stabilises pentamers. 2021 PLoS pathogens Discussion HIV K25A 44 48 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. In our experiments, P38A had a similarly reduced infectivity as K25R, but it was able to form cores in both high salt and IP6 conditions. 2021 PLoS pathogens Discussion HIV K25R;P38A 64;20 68;24 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Mutant K25N has been described as allowing similar levels of mature capsid formation as WT, suggesting that IP6-stabilisation at this position, whether in hexamers or pentamers, is not a requirement for assembly. 2021 PLoS pathogens Discussion HIV K25N 7 11 Capsid 68 74 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Mutants K25A, K25R and K25N were capable of forming capsid tubes in the presence of high salt, a widely-used condition for promoting assembly, and with similar kinetics and morphology as WT. 2021 PLoS pathogens Discussion HIV K25A;K25N;K25R 8;23;14 12;27;18 Capsid 52 58 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Single molecule TIRF studies confirmed a structural defect; K25A capsid lattices were quickly lost upon virion permeabilization and addition of IP6 failed to measurably rescue stability. 2021 PLoS pathogens Discussion HIV K25A 60 64 Capsid 65 71 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. Taken together, these data confirm that K25 is involved in the IP6-driven assembly of mature capsid cores and likely explains why no K25A mature capsids were observed in virions. 2021 PLoS pathogens Discussion HIV K25A 133 137 Capsid;Capsid 93;145 99;152 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. This suggests that inefficient mature capsid formation contributes to the reduced infectivity of K25A. 2021 PLoS pathogens Discussion HIV K25A 97 101 Capsid 38 44 33524070 A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly. We compared the behavior of K25A to P38A, a capsid instability mutant which was previously shown to have decreased infectivity and impaired reverse transcription. 2021 PLoS pathogens Discussion HIV K25A;P38A 28;36 32;40 RT;Capsid 140;44 161;50 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. 2016a), which have been validated by attenuating the inhibitory effect of Tat on DA transport in Y88F or H547A. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A;Y88F 105;97 110;101 Tat 74 77 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Although we have previously demonstrated that mutation of Cys22 residue (C22G) on Tat attenuates Tat-induced inhibition of DA transport, the underlying mechanism of C22G-induced attenuation of Tat inhibitory effect is a result of changing normal Tat protein structure folding rather than DAT-Tat interaction. 2021 Journal of neuroimmune pharmacology Discussion HIV C22G;C22G 73;165 77;169 Tat;Tat;Tat;Tat;Tat 82;97;193;246;292 85;100;196;249;295 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Consistent with the current results, our recent study has demonstrated that double mutations of Y88 and H547 (Y88F/H547A) attenuates the zinc-mediated [3H]DA uptake and [3H]WIN35,428 binding as well as increases basal substrate DA efflux. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A;Y88F 115;110 120;114 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. D381L displayed a significant reduction of total and surface DAT expression, suggesting the decreased Vmax in D381L is due to changing total DAT protein expression. 2021 Journal of neuroimmune pharmacology Discussion HIV D381L;D381L 110;0 115;5 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Determining whether double mutant D206L/H547A induces transport conformational change by MTSET assay is an interesting topic for future investigations. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A 34;40 39;45 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Furthermore, Y88F/D206L/H547A increased DA uptake potency for DA and GBR12909. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A;Y88F 18;24;13 23;29;17 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. H547A with inserted MTSET-sensitive cysteine construct (E2C-I159C/H547A) increases the sensitivity of an inserted cysteine in the position 159 in DAT to MTSET-induced reduction in DA uptake compared to WT hDAT with the same inserted cysteine construct (E2C-I159C WT hDAT) or negative control (E2C-I159A/H547A). 2021 Journal of neuroimmune pharmacology Discussion HIV H547A;H547A;I159A;I159C;I159C;H547A 66;303;297;60;257;0 71;308;302;65;262;5 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. In contrast, D381L displayed a decrease in the Vmax of DA uptake and the DA uptake potency, but increased the inhibitory potency of [3H]WIN35,428 binding for cocaine and GBR12909, suggesting that D381L alters the basal DA transport function. 2021 Journal of neuroimmune pharmacology Discussion HIV D381L;D381L 13;196 18;201 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Interestingly, our current and previous results show that neither total DAT nor surface DAT expression was altered in Y88F, D206L or H547A, however, an reduction of total and surface DAT was observed in Y88F/D206L/H547A. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A;Y88F;D206L;H547A;Y88F 208;214;203;124;133;118 213;219;207;129;138;122 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Interestingly, Y88F/D206L/H547A induced a 147 % reduction in the Vmax of DA uptake, whereas neither Y88F nor D206L altered the Vmax, suggesting no additive effects of the combination of the mutated residues on the basal DA transport. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A;Y88F;D206L;Y88F 20;26;15;109;100 25;31;19;114;104 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Moreover, D381L had no effect on Tat-induced inhibition of DA transport because D381L was only observed to bind to T-R57 with a relatively large distance compared to D206L. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;D381L;D381L 166;10;80 171;15;85 Tat 33 36 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Moreover, our previous study shows that H547A attenuates both zinc-mediated [3H]DA uptake and [3H]WIN35,428 binding as well as increases basal substrate DA efflux. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A 40 45 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Moreover, Y88F/D206L/H547A did not alter the Bmax of [3H]WIN35,428 binding but increased its binding potency. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A;Y88F 15;21;10 20;26;14 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Moreover, Y88F/D206L/H547A increased the Km of DA uptake, whereas the Km was not altered in D206L in the current study or Y88F and H547 from our previous reports. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A;Y88F;D206L;Y88F 15;21;10;92;122 20;26;14;97;126 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Next, we further characterized the role of H547A in transporter conformational transitions by assessing DA uptake with the accessibility to MTSET of an inserted cysteine (I159C) on a hDAT background. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A;I159C 43;171 48;176 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. On the other hand, we found that H547A displays enhanced the magnitude of 2-BP-induced decrease in DA uptake, suggesting that H547A-induced increased DA uptake is dependent on palmitoylation activity. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A;H547A 33;126 38;131 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Our data indicate that DA translocation more readily occurs due to changing transporter conformation to outward-open status induced by the H547A mutation, which facilitates enhanced DAT uptake. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A 139 144 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Particularly, mutations of Y88 (Y88F) and H547 (H547A) preserved and increased DA transport, respectively. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A;Y88F 48;32 53;36 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Similarly, Y88F/D206L/H547A attenuated the zinc-mediated increase in [3H]WIN35,428 binding and had no effect on basal MPP + efflux, whereas Y88F did attenuate the zinc-mediated increase in [3H]WIN35,428 binding but had no effect on basal MPP + efflux, suggesting that the triple mutant may attenuate Tat effect through an independent mechanism. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A;Y88F;Y88F 16;22;11;140 21;27;15;144 Tat 300 303 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The combination of these mutants retains single mutant H547A-mediated enhancement of DA transport and attenuates Tat inhibitory effect on DAT function. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A 55 60 Tat 113 116 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The current results show that D206L, D206L/H547A or Y88F/D206L/H547A attenuated Tat-induced inhibition of DA uptake and DAT binding, which further validate our computational prediction: two and three hydrogen bonds in the hDAT-Tat interface could be eliminated by the double and triple mutations of these residues. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A;Y88F;D206L;D206L;H547A 57;63;52;30;37;43 62;68;56;35;42;48 Tat;Tat 80;227 83;230 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The current results show that K19A attenuated the wild type Tat-induced reduction in both [3H]DA uptake and [3H]WIN35,428 binding, which strongly support the computationally predicted the DAT-Tat interaction. 2021 Journal of neuroimmune pharmacology Discussion HIV K19A 30 34 Tat;Tat 60;192 63;195 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The current results show that mutation of a novel D206 residue on hDAT (D206L) preserved normal DA uptake and attenuated Tat-induced inhibition of DA uptake, which is similar to our previous observation in Y88F. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;Y88F 72;206 77;210 Tat 121 124 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. The D206A/H547A mutant displayed a 53 % increase in the Vmax of DA uptake, which partially retains the magnitude of increased DA uptake (195 %) in H547A observed in our previous study, suggesting a critical role of the mutated H547 residue in regulating transporter activity. 2021 Journal of neuroimmune pharmacology Discussion HIV D206A;H547A;H547A 4;10;147 9;15;152 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. This is consistent with our previous report showing H547A-induced alteration of basal PKC activity. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A 52 57 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. This study further demonstrates that an allosteric modulatory mechanism may contribute to the D206L/H547A-mediated attenuation of Tat effect. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;H547A 94;100 99;105 Tat 130 133 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Through the integrated computational modeling and experimental validation, the current study further validated the hDAT-Tat complex model by mutating Lys19 (K19A) on Tat protein. 2021 Journal of neuroimmune pharmacology Discussion HIV K19A 157 161 Tat;Tat 120;166 123;169 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. Thus, these findings significantly highlight the impact of H547A mutant on the allosteric modulation of Tat interaction with DAT. 2021 Journal of neuroimmune pharmacology Discussion HIV H547A 59 64 Tat 104 107 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. We found that D206L/H547A attenuated zinc-mediated increase in [3H]WIN35,428 binding and augmented basal efflux of substrate MPP+, whereas neither zinc-mediated increase in [3H]WIN35,428 binding nor basal MPP + efflux was altered in D206L. 2021 Journal of neuroimmune pharmacology Discussion HIV D206L;D206L;H547A 14;233;20 19;238;25 33537927 Mutations of Human DopamineTransporter at Tyrosine88, Aspartic Acid206, and Histidine547 Influence Basal and HIV-1 Tat-inhibited Dopamine Transport. We have reported that mutated Lys92 (K92M) decreases DA uptake as well as total DAT protein. 2021 Journal of neuroimmune pharmacology Discussion HIV K92M 37 41 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. High-level resistance to efavirenz and nevirapine primarily resulted from the mutations K103N, L100I, and P225H. 2021 BMC infectious diseases Discussion HIV K103N;L100I;P225H 88;95;106 93;100;111 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. In case of NNRTIs, the mutation V106I, which can cause low-level resistance to doravirine, was a major cause of drug resistance. 2021 BMC infectious diseases Discussion HIV V106I 32 37 NNRTI 11 17 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. Most V179E mutations were detected in CRF55_01B, and most V179D mutations were detected in CRF01_AE, CRF07_BC, and CRF08_BC subtypes. 2021 BMC infectious diseases Discussion HIV V179D;V179E 58;5 63;10 33557775 HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China. Mutations related to NNRTI resistance were common, especially V179E (7.21%) and V179D (3.21%). 2021 BMC infectious diseases Discussion HIV V179D;V179E 80;62 85;67 NNRTI 21 26 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. Even though there is no indication of the patients being administered RAL, three of the patients in our study harbored Y143R mutation in > 20% of the population. 2021 BMC infectious diseases Discussion HIV Y143R 119 124 33632139 Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa. Previous studies on HIV-1C have shown major INI mutations at baseline in less than 5% of patients from Ethiopia (T66I, E138K, Q148R, and Q148H) and South Africa (Q148H, T66S, E92G, S147G, T66A, Y143YF and Y143H). 2021 BMC infectious diseases Discussion HIV E138K;E92G;Q148H;Q148H;Q148R;S147G;T66A;T66I;T66S;Y143F;Y143H;Y143Y 119;175;137;162;126;181;188;113;169;194;205;194 124;179;142;167;131;186;192;117;173;200;210;200 IN 44 47 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Major mutations conferring resistance to NNRTIs with K103N, Y181C, H22Y, G190A, K101E being prevalent have also been identified. 2020 The Pan African medical journal Discussion HIV G190A;H22Y;K101E;K103N;Y181C 73;67;80;53;60 78;71;85;58;65 NNRTI 41 47 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Our findings reveal major mutations conferring resistance to NRTIs with M184V, Y115F, K65R, D67N, K70E being prevalent. 2020 The Pan African medical journal Discussion HIV D67N;K65R;K70E;M184V;Y115F 92;86;98;72;79 96;90;102;77;84 NRTI 61 66 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. PI major mutations were identified with I54V, F53L, V82A being prevalent. 2020 The Pan African medical journal Discussion HIV F53L;I54V;V82A 46;40;52 50;44;56 PI 0 2 33654530 Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya. Some of these mutations have been identified in other similar studies in Kenya with K103N and M184V being predominant. 2020 The Pan African medical journal Discussion HIV K103N;M184V 84;94 89;99 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Compared with the baseline, the HIVDR mutations, such as N88D, K65R, M184VI, K103N, E138AG, V179D and P225H, still existed but the frequency gradually decreased, consistent with earlier studies. 2021 Pathogens (Basel, Switzerland) Discussion HIV E138A;E138G;K103N;K65R;M184I;M184V;N88D;P225H;V179D 84;84;77;63;69;69;57;102;92 90;90;82;67;75;75;61;107;97 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Four DRMs including D30N (1), M46I (2) and N88D (1) were detected in protease in four participants at a 5%-15% frequency, in addition to one Q58E at a frequency above 90%. 2021 Pathogens (Basel, Switzerland) Discussion HIV D30N;M46I;N88D;Q58E 20;30;43;141 24;34;47;145 PR 69 77 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. In NRTI DRMs, K65R was the highest (1.2%) at a >5% frequency, which was similar to other research results. 2021 Pathogens (Basel, Switzerland) Discussion HIV K65R 14 18 NRTI 3 7 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. N88D and Q58E are PI accessary resistance mutations. 2021 Pathogens (Basel, Switzerland) Discussion HIV Q58E;N88D 9;0 13;4 PI 18 20 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. Nevertheless, we found new low-frequency mutations such as I84V, F77L and V106A at follow-ups in this study. 2021 Pathogens (Basel, Switzerland) Discussion HIV F77L;I84V;V106A 65;59;74 69;63;79 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. The K65R mutation causes high-level resistance to tenofovir and intermediate resistance to lamivudine, which are the backbone of first- and second-line regimens. 2021 Pathogens (Basel, Switzerland) Discussion HIV K65R 4 8 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. The minority K65R mutations may become major mutations when re-initiating ART, giving rise to virological failure. 2021 Pathogens (Basel, Switzerland) Discussion HIV K65R 13 17 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. The minority mutations detected by NGS may have resulted from apolipoprotein B mRNA editing catalytic polypeptide (APOBEC)-mediated G-to-A hypermutation such as E138K, M184I and G190E in RT or spontaneous mutation during viral replication, or from PCR error, which was introduced by error-prone reverse transcriptase or PCR enzymes. 2021 Pathogens (Basel, Switzerland) Discussion HIV E138K;G190E;M184I 161;178;168 166;183;173 RT;RT 295;187 316;189 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. The most common NNRTI DRM above a 5% frequency was K103N (14.4%) in RT, which is consistent with the ART history of EFV/NVP-based first-line therapy. 2021 Pathogens (Basel, Switzerland) Discussion HIV K103N 51 56 NNRTI;RT 16;68 21;70 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. The subtype-specific differences in the K65R mutation distribution are mainly due to differences in codon usage, as it is subtype C in this region in the CRF07_BC and CRF08_BC strains. 2021 Pathogens (Basel, Switzerland) Discussion HIV K65R 40 44 33668946 HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China. We also found that the distribution of the K65R mutation was related to the HIV subtypes CRF07_BC and CRF08_BC. 2021 Pathogens (Basel, Switzerland) Discussion HIV K65R 43 47 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Another INSTIs-resistance mutation observed in our study was E157Q, which confers potential resistance to RAL and EVG, but sensitivity to DTG and BIC. 2021 Drug design, development and therapy Discussion HIV E157Q 61 66 INSTI 8 14 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. E157Q has been shown to act as a compensatory mutation due to its ability to restore damaged enzymatic activity caused by N155H or R263K substitution. 2021 Drug design, development and therapy Discussion HIV N155H;R263K;E157Q 122;131;0 127;136;5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. E157Q is a common polymorphic mutation selected by RAL treatment in HIV patients and by exposure to EVG in vitro. 2021 Drug design, development and therapy Discussion HIV E157Q 0 5 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. However, the frequency of INSTIs-resistance mutations may increase with the extensive use of ART, since E138K, a major INSTIs-resistance mutation, was also detected in our study cohort. 2021 Drug design, development and therapy Discussion HIV E138K 104 109 INSTI;INSTI 26;119 32;125 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. In Morocco, 5.2% of the study sample contained secondary mutations (L74IM, T97A), while no primary INSTIs-resistance mutations were detected among 77 ART-naive patients. 2021 Drug design, development and therapy Discussion HIV L74I;L74M;T97A 68;68;75 73;73;79 INSTI 99 105 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. One major (E138K) and one accessory (E157Q) INSTIs-resistance mutation were detected in two different samples. 2021 Drug design, development and therapy Discussion HIV E138K;E157Q 11;37 16;42 INSTI 44 50 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Similar to the study conducted by Liu et al, who first reported the presence of the E157Q mutation among Chinese ART-naive patients in 2019, the frequency of the integrase E157Q mutation was very low in China. 2021 Drug design, development and therapy Discussion HIV E157Q;E157Q 84;172 89;177 IN 162 171 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. The prevalence of the E157Q polymorphic mutation was 2.7% in INSTIs-naive patients from 17 French clinical centers, and 2.4% in ART-naive patients in Italy. 2021 Drug design, development and therapy Discussion HIV E157Q 22 27 INSTI 61 67 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. These studies have demonstrated that the E157Q mutation itself has minimal effects on RAL and DTG activity and viral infectivity. 2021 Drug design, development and therapy Discussion HIV E157Q 41 46 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. Usually, E138K is a nonpolymorphic mutation emerging in patients with virological treatment failure after receiving RAL, EVG, or DTG. 2021 Drug design, development and therapy Discussion HIV E138K 9 14 33679129 Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China. We report for the first time the identification of the integrase E138K mutation associated with INSTIs-resistance in HIV patients in China. 2021 Drug design, development and therapy Discussion HIV E138K 65 70 IN;INSTI 55;96 64;102 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. A previous study showed an increase in VL after discontinuing lamivudine despite the presence of the M184V mutation in plasma, suggesting a residual antiviral effect of this drug. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 101 106 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. However, some patients included in ART-PRO had a low minority of M184V detectable by ultra-deep sequencing, although the long-term clinical impact of this low burden of archived resistance is unknown and deserves further study. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 65 70 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. However, the nine youths in our study without M184V in their pDNA presented lower time under undetectable VL than those with M184V. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V;M184V 46;125 51;130 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. In our study cohort, it can be seen that previously archived mutations such as M184V are lost over time and after virological suppression. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 79 84 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. In the MOBIDIP cohort, dual maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V at first-line treatment failure. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 164 169 PR 61 69 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. It may be possible that the loss of M184V in PBMCs might be associated with the longer time under lamivudine/emtricitabine exposure, although this should be confirmed in larger study cohorts. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 36 41 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Only 3/12 patients (25%) with pDNA sequence under study presented the M184V mutation in their pDNA and none presented K65R/E/N. 2021 The Journal of antimicrobial chemotherapy Discussion HIV K65E;K65N;K65R;M184V 118;118;118;70 126;126;126;75 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Other studies showed that switch regimens, as bictegravir/emtricitabine/tenofovir alafenamide and abacavir/lamivudine/dolutegravir triple therapy and ART-PRO for dual therapy, were successful in the absence of historical M184V in baseline PBMCs. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 221 226 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Previous studies have suggested that a prolonged time with undetectable VL is associated with clearance of M184V in PBMCs in some adult cohorts. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 107 112 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. Some publications have showed that lamivudine/emtricitabine-based regimens might work in the presence of M184V in historical Sanger baseline sequences. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 105 110 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. These results suggest that measurement of pDNA may be useful to detect the presence of M184V/I mutation in vertically HIV-infected youths with this mutation previously detected in plasma. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184I;M184V 87;87 94;94 HIV infections 118 130 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. This is the first study analysing the existence of lamivudine- or emtricitabine resistance-conferring mutations in pDNA (M184V/I and/or K65R/E/N) in historic plasma genotypes in a cohort of vertically HIV-infected patients under ART after at least 1 year of viraemia suppression. 2021 The Journal of antimicrobial chemotherapy Discussion HIV K65E;K65N;K65R;M184I;M184V 136;136;136;121;121 144;144;144;129;129 HIV infections 201 213 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. We also emphasize the absence of detection of M184V by population sequencing of PBMCs after years of complete virological suppression. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V 46 51 33734374 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. We also observed that these three youths had more time exposed to lamivudine/emtricitabine before the first detection of M184V in their historic plasma, but less time exposed to these drugs from the first detection in plasma to the PBMCs sampling, compared with the nine youths without M184V in their pDNA. 2021 The Journal of antimicrobial chemotherapy Discussion HIV M184V;M184V 121;286 126;291 33800269 Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals. However, the presence of three mutations (G140S, Q148H, and S147G) pose a higher risk of failing second-generation drugs. 2021 International journal of environmental research and public health Discussion HIV G140S;Q148H;S147G 42;49;60 47;54;65 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. A recent study also showed that the G176R mutation in Nef selectively disrupts CD4 downregulation, but not SERINC5 antagonism by Nef, likely by disruption of the AP-2 binding and the uncoupling of these two functions of Nef. 2021 Viruses Discussion HIV G176R 36 41 Nef;Nef;Nef 54;129;220 57;132;223 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. However, no effect of the H116N mutation in Nef on disease progression was observed, indicating that the change in functionality associated with this polymorphism is not essential or is too small to affect HIV-1 replication in vivo. 2021 Viruses Discussion HIV H116N 26 31 Nef 44 47 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. However, these mutations, except for 8R, 157N and R178G, have no significant effect on HIV-1 pathogenesis. 2021 Viruses Discussion HIV R178G 50 55 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. However, we did observe that the N51T, H116N and 188S mutations increased HIV-1 infectivity when the virus was produced in the presence of SERINC3. 2021 Viruses Discussion HIV H116N;N51T 39;33 44;37 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. Interestingly, the presence of the R178G mutation in Nef was associated with accelerated progression to AIDS and AIDS-related death in our cohort. 2021 Viruses Discussion HIV R178G 35 40 Nef 53 56 AIDS;AIDS 104;113 108;117 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. Serine at position 188 has previously been described with increased SERINC3 internalization function, confirming our observations, while the N51T mutation has only been associated with a modest increased functionality to internalize SERINC5. 2021 Viruses Discussion HIV N51T 141 145 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The H116N mutation has been reported to have a negative effect on infectivity in the presence of SERINC5 but had no effect on SERINC3 internalization, contradicting our observations. 2021 Viruses Discussion HIV H116N 4 9 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The lower ability of the R178G mutation to counteract SERINC3 and -5 may indicate that, during the course of infection, the selective pressure of this restriction protein is lost in these individuals, explaining the selective outgrowth of HIV-1 variants containing the R178G mutation in Nef. 2021 Viruses Discussion HIV R178G;R178G 25;269 30;274 Nef 287 290 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. The R178G polymorphism located in the ERE177 region was observed in almost 18% of the primary isolates. 2021 Viruses Discussion HIV R178G 4 9 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. These data could also indicate that the observed accelerated disease progression associated with the R178G mutation may be related to the loss of the ability of Nef to downregulate CD4. 2021 Viruses Discussion HIV R178G 101 106 Nef 161 164 33800773 Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction. We observed that this polymorphism (S163C) was present in 39.8% of the primary HIV-1 variants tested and was associated with increased Nef activity to counteract SERINC5 and, consequently, with higher HIV-1 infectivity. 2021 Viruses Discussion HIV S163C 36 41 Nef 135 138 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. A comparative analysis of the genotypic variation in the HIV-1 PR from subtype B and C from laboratory-generated sequences and publicly available database showed the L90M occur more in HIV-1 subtype B PR than HIV-1 PR variants from subtype C. 2021 Biomolecules Discussion HIV L90M 166 170 PR;PR;PR 63;201;215 65;203;217 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. In addition, most of the mutations harbored by the mutant HIV-1 PR variants in this study are LPV resistance mutations except L33F (in MUT-2) and L76V (in MUT-2 and 3). 2021 Biomolecules Discussion HIV L33F;L76V 126;146 130;150 PR 64 66 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. In addition, the F53L mutation in MUT-3, though a minor mutation in the flap, is associated with the loss of the hydrophobic bond interaction between phenylalanine's side chain at position 53 of chain A, with isoleucine at position 50 on the second PR subunit (chain B). 2021 Biomolecules Discussion HIV F53L 17 21 PR 249 251 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The L76V is also commonly seen in highly mutated HIV-1 PR variants resistant to DRV. 2021 Biomolecules Discussion HIV L76V 4 8 PR 55 57 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The L76V mutation found in MUT-2 and MUT-3 in this study has been shown previously to confer resistance to several HIV-1 PIs through the local rearrangement of the hydrophobic core. 2021 Biomolecules Discussion HIV L76V 4 8 PI 121 124 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The L90M mutation is not commonly seen in HIV-1 subtype C PR, this mutation may have evolved from previous exposure of the patients to PIs like nelfinavir (NFV) and saquinavir (SQV) before treatment with the LPV containing regimen. 2021 Biomolecules Discussion HIV L90M 4 8 PI;PR 135;58 138;60 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The L90M observed in MUT-3 is another mutation associated with the alteration of the HIV-1 PR hydrophobic core flexibility and decreased dimer stability. 2021 Biomolecules Discussion HIV L90M 4 8 PR 91 93 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The M46I and I54V flap mutations found in the mutants in this study have been shown in a previous study to be associated with decreased binding affinity of HIV-1 PR to PIs, even though they are not active site mutations. 2021 Biomolecules Discussion HIV I54V;M46I 13;4 17;8 PI;PR 168;162 171;164 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The presence of the V82A mutation in all the HIV-1 PR mutant variants may have contributed significantly to the reduced binding affinity of the mutant HIV-1 PR variants to LPV and DRV. 2021 Biomolecules Discussion HIV V82A 20 24 PR;PR 51;157 53;159 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. The V82A mutation is common in patients failing LPV therapy and emerges from the sustained use of LPV during virological failure. 2021 Biomolecules Discussion HIV V82A 4 8 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. These mutations, in the presence of active site mutations, like V82A and I84V, cause high-level cross-resistance to several HIV-1 PIs. 2021 Biomolecules Discussion HIV I84V;V82A 73;64 77;68 PI 130 133 33805099 Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch. This, therefore, shows that the open and increased flap flexibility (Figure 8A-F) in the mutant HIV-1 PR variant may be a product of the distorted hydrophobic core, as shown by the increased SASA in addition to the presence of the flap mutations M46I and I54V present in all the mutants studied. 2021 Biomolecules Discussion HIV I54V;M46I 255;246 259;250 PR 102 104 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. Comparable with others, amongst individuals with prior exposure to RAL, the most common mutations selected were N155H (n = 4), Q148R (n = 4), S147G (n = 4) and E138K (n = 3) as others have similarly found. 2021 Viruses Discussion HIV E138K;N155H;Q148R;S147G 160;112;127;142 165;117;132;147 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. Compared with a similar cohort of patients from clinical trials, the selection of major integrase DRM- R263K was common. 2021 Viruses Discussion HIV R263K 103 108 IN 88 97 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. In our study, E138K (n = 5), S147G (n = 4), Q148R (n = 4) and N155H (n = 4) where the most frequent INSTI DRMs identified. 2021 Viruses Discussion HIV E138K;N155H;Q148R;S147G 14;62;44;29 19;67;49;34 INSTI 100 105 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. It was recently shown that it is only upon the development of the T97A mutation that variants harboring Q148H and G140S Integrase mutations started to have increased VLs. 2021 Viruses Discussion HIV G140S;Q148H;T97A 114;104;66 119;109;70 IN 120 129 33807382 HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. This is in contrast to Y143C/R/H (n = 12), N155H (n = 9) and T97A(n = 13) from a similar study in the region where HIV-1C also predominates. 2021 Viruses Discussion HIV N155H;T97A;Y143C;Y143H;Y143R 43;61;23;23;23 48;65;32;32;32 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Hence, CA: I201V mutation may cause a conformational change in the immature Gag lattice which may lead to an increase in the infectivity and replicative fitness of the virus in the presence of BVM analog. 2021 Retrovirology Discussion HIV I201V 11 16 Gag;Capsid 76;7 79;9 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Hence, it is possible that the K3016 SP1: A1V mutation may confer resistance to the compound CV-8612 in a similar manner. 2021 Retrovirology Discussion HIV A1V 42 45 SP1 37 40 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. However, the mutation at SP1-A1V may confer resistance by destabilizing Gag thus making the CA-SP1 cleavage site accessible to the viral protease. 2021 Retrovirology Discussion HIV A1V 29 32 PR;SP1;SP1;Gag;Capsid 137;25;95;72;92 145;28;98;75;94 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. In contrast, the HIV-1 subtype B CA:I1201V mutant conferred resistance but not compound dependence against MIs: GSK3532795 and PF-46396. 2021 Retrovirology Discussion HIV I1201V 36 42 Capsid 33 35 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Neyret et al., reported that SP1:A1V mutation in HIV-1 subtype B NL4-3 virus suppressed the interaction of a BVM analog EP-39 with CA-SP1(A1V)-NC Gag peptide in comparison to the WT. 2021 Retrovirology Discussion HIV A1V;A1V 33;138 36;141 SP1;SP1;Gag;NC;Capsid 29;134;146;143;131 32;137;149;145;133 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. Resistance selection experiments performed by culturing the K3016 virus in the presence of the BVM analogs led to the emergence of two mutations, SP1: A1V and CA: I120V. 2021 Retrovirology Discussion HIV A1V;I120V 151;163 154;168 SP1;Capsid 146;159 149;161 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The second mutant K3016 CA:I201V was identified in the presence of BVM analog CV-8613 and conferred partial resistance and compound dependence on the HIV-1 subtype C virus consistent with our previous study using another MI, PF-46396. 2021 Retrovirology Discussion HIV I201V 27 32 Capsid 24 26 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. The SP1: A1V was the most prevalent mutation that conferred resistance against all the MIs tested. 2021 Retrovirology Discussion HIV A1V 9 12 SP1 4 7 33836787 A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors. This phenotype of the HIV-1 subtype C CA:I201V mutant reflected a unique characteristic of this virus. 2021 Retrovirology Discussion HIV I201V 41 46 Capsid 38 40 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. The inference is that the original resistant mutants exhibited unstable Gag lattices in the absence of the compound, which stabilizes the lattice, and T8I mutation phenocopies the compound by stabilizing the lattice, which then becomes hyper-stable in the absence of a destabilizing mutation. 2021 Communications biology Discussion HIV T8I 151 154 Gag 72 75 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. The SP1-T8I mutation is a stabilizing compensatory mutation selected for during the passage of MI-dependent virus. 2021 Communications biology Discussion HIV T8I 8 11 SP1 4 7 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. The T8I mutation was acquired as a second-site mutation that restores assembly and maturation to the BVM- and PF-96-dependent mutants, but the T8I single mutant exhibited a maturation defect with inefficient cleavage at CA-SP1. 2021 Communications biology Discussion HIV T8I;T8I 4;143 7;146 SP1;Capsid 223;220 226;222 33863979 CryoET structures of immature HIV Gag reveal six-helix bundle. We show that the T8I mutation alters the cleavage sequence in HIV-1 maturation and impairs the processing of both SP1 boundaries, suggesting that a finely tuned SP1 stability is required to balance between lattice assembly, proper maturation and infectivity. 2021 Communications biology Discussion HIV T8I 17 20 SP1;SP1 114;161 117;164 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. A study by Axel Fun et al., 2010, showed that this secondary mutation enhances N155H-mediated resistance and partially restores the reduced replication caused by N155H. 2021 BMC infectious diseases Discussion HIV N155H;N155H 79;162 84;167 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Abraham et al., 2013, showed that the T66A mutant occurs within the two distal sheet from the DDE triad motif. 2021 BMC infectious diseases Discussion HIV T66A 38 42 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. E157Q acts as a compensatory mutation and individually has a negligible effect on the susceptibility to INSTIs; however, a combination of E157Q with other INSTI RAMs may lead to reduced susceptibility to INSTIs. 2021 BMC infectious diseases Discussion HIV E157Q;E157Q 138;0 143;5 INSTI;INSTI;INSTI 104;155;204 110;160;210 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Four major INSTIs mutations were found within the database sequences: T66A, Q148H, N155H and R263K. 2021 BMC infectious diseases Discussion HIV N155H;Q148H;R263K;T66A 83;76;93;70 88;81;98;74 INSTI 11 17 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. In our study, we detected L74M mutations at a frequency > 20%, which is not surprising since, nearly 10% of ARV-Naive patients infected with CRF02_AG viruses harbours L74M mutations. 2021 BMC infectious diseases Discussion HIV L74M;L74M 26;167 30;171 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. In our study, we observed five IN accessory RAMs; namely Q95K, T97A, G149A, E157Q and D232N. 2021 BMC infectious diseases Discussion HIV D232N;E157Q;G149A;Q95K;T97A 86;76;69;57;63 91;81;74;61;67 IN 31 33 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Individuals containing E157Q mutation in combination with other IN RAMs showed reduced susceptibility to DTG. 2021 BMC infectious diseases Discussion HIV E157Q 23 28 IN 64 66 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Interestingly, the mutation E157Q occurred within the stable alpha-helix secondary structure element and made more contacts with DNA (stabilizing viral DNA complex), while the D232N mutation occurred within the stable Beta-sheet secondary structure element and in close proximity to the flexible G140's loop region suggesting that these changes can affect the protein conformation and thereby interfere with drug binding leading to resistance. 2021 BMC infectious diseases Discussion HIV D232N;E157Q 176;28 181;33 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Moreover, another rare nonpolymorphic accessory resistance mutation Q95K confers little if any effect on drug susceptibility to INSTIs. 2021 BMC infectious diseases Discussion HIV Q95K 68 72 INSTI 128 134 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Most of the variants noted in our study were shown to destabilise the protein structure, except for one mutation Q95K, that showed to exert a slightly stabilising effect on the protein structure and no changes in the number of polar contacts with neighbouring residues making it unlikely to affect the IN protein structure. 2021 BMC infectious diseases Discussion HIV Q95K 113 117 IN 302 304 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Q148H and N155H mutations are thought to trigger conformational changes within the catalytic pocket that result in lower binding affinity of INSTIs to IN. 2021 BMC infectious diseases Discussion HIV N155H;Q148H 10;0 15;5 INSTI;IN 141;151 147;153 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. R263K displayed moderate level resistance against EVG (12-fold) and seems to confer low-level resistance against DTG. 2021 BMC infectious diseases Discussion HIV R263K 0 5 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. T97A mutation can reduce EVG susceptibility by 3-fold and combination of T97A mutation with other INSTI RAMs lead to reduced susceptibility to RAL and DTG. 2021 BMC infectious diseases Discussion HIV T97A;T97A 73;0 77;4 INSTI 98 103 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. The close proximity of the T66A/I/K variants to the viral DNA 3' end and mutation N155H, could sterically hamper viral DNA binding and/or metal ion coordination with DTG. 2021 BMC infectious diseases Discussion HIV N155H;T66A;T66I;T66K 82;27;27;27 87;35;35;35 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. The findings revealed accessory mutations E157Q and D232N had the potential to reduce and or prevent DTG binding to HIV-1 CRF02_AG IN structure based on the loss of MG ion interactions, while known RAM's does not seem to influence DTG drug binding. 2021 BMC infectious diseases Discussion HIV D232N;E157Q 52;42 57;47 IN 131 133 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. The variant T66A which is normally selected by EVG treatment, was detected in 0.3% of our sequence cohort. 2021 BMC infectious diseases Discussion HIV T66A 12 16 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. These mutations are located in close proximity to the Integrase's active site and each mutation significantly reduces viral fitness by 92-fold for Q148R, 30-fold for N155H. 2021 BMC infectious diseases Discussion HIV N155H;Q148R 166;147 171;152 IN 54 63 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. This L74M mutation has minimal if any effect against susceptibly of INSTIs, but in combination with mutations at positions 140 and 148, it reduces susceptibility of DTG. 2021 BMC infectious diseases Discussion HIV L74M 5 9 INSTI 68 74 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. This variant is associated with 5-fold reduced susceptibility to EVG, however, T66A also bears cross-resistance to DTG and is selected by RAL. 2021 BMC infectious diseases Discussion HIV T66A 79 83 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. This was further explored by performing interaction analysis between the drug DTG and energy minimized structures of the WT and mutants T66A, T97A, Q148H, N155H, E157Q, R263K and D232N. 2021 BMC infectious diseases Discussion HIV D232N;E157Q;N155H;Q148H;R263K;T66A;T97A 179;162;155;148;169;136;142 184;167;160;153;174;140;146 33892628 Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations. Two principal mutation pathways identified from our study that reduces susceptibility to RAL are Q148H/K/R and N155H. 2021 BMC infectious diseases Discussion HIV N155H;Q148H;Q148K;Q148R 111;97;97;97 116;106;106;106 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. A subgroup analysis of the TANGO study demonstrated no impact of archived NRTI resistance on virologic outcomes through Week 48 with 4/4 patients found to have an archived M184V/I mutation achieving virologic suppression. 2021 AIDS research and therapy Discussion HIV M184I;M184V 172;172 179;179 NRTI 74 78 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Among the latter, 54% had a prior history of virologic failure and 10% had a documented M184V/I on the last genotype. 2021 AIDS research and therapy Discussion HIV M184I;M184V 88;88 95;95 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Among the three patients on functional dual therapy with persistent viremia and documented non-adherence, two were on DTG/ABC and only had baseline M184V/I whereas the other was on DTG/TDF and had baseline M184V/I, M41L and T215Y. 2021 AIDS research and therapy Discussion HIV M184I;M184I;M184V;M184V;M41L;T215Y 148;206;148;206;215;224 155;213;155;213;219;229 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. At baseline, half had a CD4+ T-cell count of < 200 cells/mm3 and 82% had a baseline M184V/I mutation plus >= 1 additional NRTI RAM. 2021 AIDS research and therapy Discussion HIV M184I;M184V 84;84 91;91 NRTI 122 126 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Both had baseline M184V/I without additional NRTI mutations. 2021 AIDS research and therapy Discussion HIV M184I;M184V 18;18 25;25 NRTI 45 49 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. However, in the patient on DTG/TDF this "hypersensitizing" effect may have been reduced by the presence of baseline M41L and T215Y which in combination are associated with low-to-intermediate-level TDF resistance and may have contributed to persistent viremia in this patient. 2021 AIDS research and therapy Discussion HIV M41L;T215Y 116;125 120;130 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. In addition to reduced 3TC and FTC susceptibility, the M184V/I mutation is associated with low-level ABC resistance and may have contributed to persistent viremia in those on DTG/ABC. 2021 AIDS research and therapy Discussion HIV M184I;M184V 55;55 62;62 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. In our cohort, virologic suppression was observed among 82% of patients, all of whom had a historical M184V/I mutation and in the DAWNING study, 84% of those in the DTG arm achieved virologic suppression despite 71% of these patients having a baseline M184V/I. 2021 AIDS research and therapy Discussion HIV M184I;M184I;M184V;M184V 102;252;102;252 109;259;109;259 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. In the patient on DTG/ABC, the reduction in ABC susceptibility conferred by the M184V/I may have contributed to persistent viremia. 2021 AIDS research and therapy Discussion HIV M184I;M184V 80;80 87;87 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. More recently, the LAMRES study has also demonstrated no difference in the probability of VF among those switching to DTG/3TC when stratifying for the presence versus absence of historical M184V/I through 2 years (9.2% vs. 2021 AIDS research and therapy Discussion HIV M184I;M184V 189;189 196;196 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Nonetheless, 32/39 patients in our cohort, 22% of whom were viremic at baseline with similar patterns of baseline resistance (all with M184V/I and over half with >= 1 additional NRTI RAM) on DTG-based functional mono-or dual therapy achieved or maintained virologic suppression. 2021 AIDS research and therapy Discussion HIV M184I;M184V 135;135 142;142 NRTI 178 182 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Of those on functional monotherapy, one was on DTG/RPV and had baseline E138E/K which reduces RPV susceptibility. 2021 AIDS research and therapy Discussion HIV E138E;E138K 72;72 79;79 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. The other was on DTG/ABC/3TC and had baseline M184V/I, L74I, M41L and T215Y, the combination of which severely reduces susceptibility to 3TC and ABC. 2021 AIDS research and therapy Discussion HIV L74I;M184I;M184V;M41L;T215Y 55;46;46;61;70 59;53;53;65;75 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. There was no difference in results when stratifying based on presence of historical M184V/I or history of VF. 2021 AIDS research and therapy Discussion HIV M184I;M184V 84;84 91;91 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. This may be due to several factors which include the ability to suppress and maintain low viral loads on 3TC due to impaired viral fitness associated with the M184V/I mutation and the delay in emergence of additional drug resistance mutations associated with DTG in the presence of M184V/I as has been observed in vitro. 2021 AIDS research and therapy Discussion HIV M184I;M184I;M184V;M184V 159;282;159;282 166;289;166;289 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. Though use of DTG/3TC is not indicated among those with a history of M184V/I, these findings suggest that the presence of this mutation does not significantly impact virologic outcomes. 2021 AIDS research and therapy Discussion HIV M184I;M184V 69;69 76;76 33941212 Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV. To date, several studies have evaluated the efficacy of DTG/3TC in the setting of pre-existing NRTI resistance including among those with an M184V/I mutation. 2021 AIDS research and therapy Discussion HIV M184I;M184V 141;141 148;148 NRTI 95 99 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Despite their small number, the 3 study patients with TAMs while on TDF and, another K65R and Y115F while on AZT hint that PDR to NRTI circulates in our study population. 2021 Infectious diseases Discussion HIV K65R;Y115F 85;94 89;99 NRTI 130 134 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. EFV and NVP have a lower genetic barrier, thus facilitating the selection of K103N and Y181C mutations. 2021 Infectious diseases Discussion HIV K103N;Y181C 77;87 82;92 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. In subgroup analysis of DR, most widespread DRMs among failing patients were 3TC-resistance M184V and NVP-resistance K103N. 2021 Infectious diseases Discussion HIV K103N;M184V 117;92 122;97 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. Tang et al in their meta-analysis found that NVP increases the risk of TAMs and K65R, which potentially confers high-level DR to AZT and TDF, respectively. 2021 Infectious diseases Discussion HIV K65R 80 84 34025122 High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat. The multicentric study by Villabona-Arenas et al showed a similar trend, reporting 86.8% of M184V and 49.7% of K103N in 1288 patients failing first-line regimens in 10 countries of WCA. 2021 Infectious diseases Discussion HIV K103N;M184V 111;92 116;97 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Another limitation in this study was the lack of samples with M184V and V106M, making it difficult to draw a conclusion on the performance of PANDAA in detecting V106M and M184V. 2020 AAS open research Discussion HIV M184V;M184V;V106M;V106M 62;172;72;162 67;177;77;167 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. By using PANDAA, we targeted the most likely mutations to develop to these medications in HIV-1 subtype C, the M184V, K103N and V106M mutations in reverse transcriptase, a targeted and cost-effective approach to genotyping is possible . 2020 AAS open research Discussion HIV K103N;M184V;V106M 118;111;128 123;116;133 RT 147 168 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Common drug resistance mutations associated with resistance to efavirenz include K103N (AAA/G to AAC/T) and V106M . 2020 AAS open research Discussion HIV K103N;V106M 81;108 86;113 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. Firstly, we only examined the most common relevant resistant mutations, V106M, K103N and M184V of the reverse transcriptase; therefore, there was a limited number of positive mutations available for analysis. 2020 AAS open research Discussion HIV K103N;M184V;V106M 79;89;72 84;94;77 RT 102 123 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. In one hundred and three samples included in our study, the use of PANDAA assay enabled detection of K103N in 3 antiretroviral naive individuals. 2020 AAS open research Discussion HIV K103N 101 106 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. The data generated by our study confirm the ability of PANDAA to detect K103N HIV drug resistance mutation as a point mutation assay, and these data correspond to Sanger sequencing data. 2020 AAS open research Discussion HIV K103N 72 77 34036243 Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naive HIV-1 Subtype C-infected patients in Botswana. The key M184V (ATG to GTG) mutation in HIV-1 RT is associated with high-level resistance to the lamivudine (3TC) and emtricitabine (FTC) ; however, M184V has been shown to rapidly decay in the absence of treatment as a result of its impact on viral fitness . 2020 AAS open research Discussion HIV M184V;M184V 8;148 13;153 RT 45 47 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Conversely, four of the T215 revertant mutations, T215C/D/E/S had treatment/naive prevalence ratios of about 1.0 raising the question of whether these mutations will remain useful for the ongoing surveillance of clinically meaningful transmitted NRTI resistance. 2021 Viruses Discussion HIV T215C;T215D;T215E;T215S 50;50;50;50 61;61;61;61 NRTI 246 250 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Even though they currently remain rare in RTI-naive persons, the tenofovir-associated mutations K65N, T69deletion, and K70G/N/Q/T were identified as potentially useful additions to an expanded NRTI SDRM list, because of the importance of tenofovir for all first-line regimens. 2021 Viruses Discussion HIV K65N;K70G;K70N;K70Q;K70T 96;119;119;119;119 100;129;129;129;129 NRTI;RT 193;42 197;45 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Four PI-SDRMs (M46L, F53Y, V82L, and I85V) had relatively low treated/naive prevalence ratios. 2021 Viruses Discussion HIV F53Y;I85V;M46L;V82L 21;37;15;27 25;41;19;31 PI 5 7 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. However, M46I remains an important DRM for lopinavir and atazanavir, although it may continue to occur at minimally elevated levels in the aforementioned subtypes. 2021 Viruses Discussion HIV M46I 9 13 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Moreover, F53Y, V82L, and I85V have not been linked to reduced susceptibility to the currently used PIs raising the question of whether these mutations will remain useful for the ongoing surveillance of clinically meaningful transmitted PI resistance. 2021 Viruses Discussion HIV F53Y;I85V;V82L 10;26;16 14;30;20 PI;PI 100;237 103;239 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Our analysis of NNRTI-SDRMs found that there were few major changes in their overall prevalence in either RTI-naive or NNRTI-experienced persons with the exception of V106M which became more prevalent in NNRTI-experienced persons because of the increased proportion of subtype C viruses increased from between the two time periods. 2021 Viruses Discussion HIV V106M 167 172 NNRTI;NNRTI;NNRTI;RT 16;119;204;106 21;124;209;109 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Six candidate NNRTI-SDRMs were identified as potentially useful additions to an expanded NNRTI SDRM list because they are associated with reduced susceptibility to rilpivirine (E138K/Q, V179L, and H221Y) and doravirine (F227L/C) and because they increased in prevalence since 2009. 2021 Viruses Discussion HIV E138K;E138Q;F227C;F227L;H221Y;V179L 177;177;220;220;197;186 184;184;227;227;202;191 NNRTI;NNRTI 14;89 19;94 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The continued prevalence of thymidine analog mutations in RTI-naive persons since 2009 despite the decline in thymidine analog use has been reported in several studies and reflects the fact that with the exception of T215Y/F, the thymidine analog mutations display minimally reduced replication fitness. 2021 Viruses Discussion HIV T215F;T215Y 217;217 224;224 RT 58 61 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The potential for M46I/L to occur at low levels in subtype A and CRF01_AE populations without previous PI exposure was recognized at the time the 2009 SDRM list was developed and in several subsequent analyses. 2021 Viruses Discussion HIV M46I;M46L 18;18 24;24 PI 103 105 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. The two SDRMs that increased in prevalence, I50L and V47A, are associated with reduced susceptibility to atazanavir and lopinavir, respectively. 2021 Viruses Discussion HIV I50L;V47A 44;53 48;57 34064774 Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance. Three candidate PI-SDRMs (L10F, T74P, and L89V) were identified as potentially useful additions to an expanded PI SDRM list because they are accessory darunavir-associated resistance mutations. 2021 Viruses Discussion HIV L10F;L89V;T74P 26;42;32 30;46;36 PI;PI 16;111 18;113 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Along with the most common mutations, M184V rates presented a decrease over the yrs (76.88% in 2008 to 51.48% in 2017). 2021 International journal of molecular sciences Discussion HIV M184V 38 43 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Also in line with previous studies is the finding of M184V (65.53%), K103N (40.20%), and M41L (17.21%) as the most common SDRM. 2021 International journal of molecular sciences Discussion HIV K103N;M184V;M41L 69;53;89 74;58;93 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. As for K65R, it is selected by TDF and by other NRTI including abacavir (ABC) and 3TC, decreasing viral susceptibility to most of these drugs. 2021 International journal of molecular sciences Discussion HIV K65R 7 11 NRTI 48 52 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Collectively, these studies suggest that the genetic or sociodemographic characteristics of the population treated with TDF might be influencing the K65R levels. 2021 International journal of molecular sciences Discussion HIV K65R 149 153 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Even though several studies support almost inexistent K65R transmission rates, Rhee and co-works present evidence of higher levels of transmitted K65R, especially in low- and middle-income countries. 2021 International journal of molecular sciences Discussion HIV K65R;K65R 54;146 58;150 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Furthermore, our results suggest that K65R overlapping peptides can be increasingly recognized by HLA-B27, a HLA that is linked with lower viral loads and slower diseased progression to AIDS. 2021 International journal of molecular sciences Discussion HIV K65R 38 42 AIDS 186 190 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Furthermore, we observed a clear increase in K65R reverse transcriptase SDRM that is an additional problem in Brazil that could have been aggravated by the circulation of HIV-1 subtype C and the HLA class I makeup of the population. 2021 International journal of molecular sciences Discussion HIV K65R 45 49 RT 50 71 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. However, although an increasing trend was identified in a cohort from India, several studies report a decrease on K65R levels over the years in other countries. 2021 International journal of molecular sciences Discussion HIV K65R 114 118 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. However, in these cases, high prevalence rates of M184V, which is also selected by FTC, and K65R as found in our study population, might compromise the efficacy of PrEP. 2021 International journal of molecular sciences Discussion HIV K65R;M184V 92;50 96;55 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. In our phylogenetic analysis we found 21 transmission clusters containing at least two sequences with the K65R mutation. 2021 International journal of molecular sciences Discussion HIV K65R 106 110 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Indeed, we found much higher viral loads in patients harboring K65R mutation when compared with the rest of our cohort population. 2021 International journal of molecular sciences Discussion HIV K65R 63 67 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. K103N was previously reported as one of the most commonly acquired SDRM in Brazil in association with the use of EFV. 2021 International journal of molecular sciences Discussion HIV K103N 0 5 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. K65R has been associated with diminished viral fitness and replication, which has been linked with decreased transmission capacity. 2021 International journal of molecular sciences Discussion HIV K65R 0 4 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. M184V, the most prevalent, is a NRTI mutation selected by 3TC and associated with impaired viral fitness and hypersensitization to other NRTI, including AZT and TDF. 2021 International journal of molecular sciences Discussion HIV M184V 0 5 NRTI;NRTI 32;137 36;141 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Moreover, K103N and P225H, both frequent NNRTI SDRM, remained stable over the yrs. 2021 International journal of molecular sciences Discussion HIV K103N;P225H 10;20 15;25 NNRTI 41 46 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Moreover, minimum spanning network analysis supported the occurrence of events of K65R transmission in at least seven of these clusters. 2021 International journal of molecular sciences Discussion HIV K65R 82 86 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Nonetheless, it is important to highlight that the percentage of PLWH infected with a virus harboring M148V remained very high and above 50% after 2013. 2021 International journal of molecular sciences Discussion HIV M148V 102 107 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. P225H is also selected by EFV and generally occurs in the presence of K103N, synergically increasing EFV resistance. 2021 International journal of molecular sciences Discussion HIV K103N;P225H 70;0 75;5 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Previous work reported that K65R mutation presented varied prevalence distribution throughout time in different Brazilian regions. 2021 International journal of molecular sciences Discussion HIV K65R 28 32 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Reinheimer and colleagues suggest that the decline on K65R prevalence rates is linked with the increasing usage of single tablet ART regimens and the inclusion of AZT on the used treatment regimen, which has been liked with K65R development suppression. 2021 International journal of molecular sciences Discussion HIV K65R;K65R 54;224 58;228 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. Strikingly, in our nationwide work in Brazil we found that K65R was the only SDRM that followed an accentuated increase in prevalence over the studied years (2.23% in 2008 to 12.11% in 2017). 2021 International journal of molecular sciences Discussion HIV K65R 59 63 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. The fact that Brazil presents a low prevalence of the HLA-B27, when in comparison with other regions, might have contributed to K65R expansion in this country. 2021 International journal of molecular sciences Discussion HIV K65R 128 132 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. The increasing and preferential usage of TDF in the clinical practice, including in a context of a failing regimen, could be the primordial reason for the significant expansion of K65R as other studies show a higher prevalence of this mutation in patients failing ART treatment. 2021 International journal of molecular sciences Discussion HIV K65R 180 184 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. This increase in K65R was mainly found in association with the use of TDF and is particularly relevant in combination with the high M184V levels found in the study population suggesting that the efficacy of PrEP might be compromised. 2021 International journal of molecular sciences Discussion HIV K65R;M184V 17;132 21;137 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. We propose that the lack of universal baseline HIV-1 DRM screening to inform on effective ART regimens resulted in high levels of SDRM, such as M184V, K103N, and M41L underlying many cases of treatment failure in Brazil not only from 2008-2012 but also continuing from 2013-2017. 2021 International journal of molecular sciences Discussion HIV K103N;M184V;M41L 151;144;162 156;149;166 34069929 Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil. work suggests that the found decline of tenofovir K65R selection rate in Portugal, between 2002 and 2010, is mainly caused by changes on treatment guidelines over the years and by the increased usage of combination of TDF and emtricitabine (FTC). 2021 International journal of molecular sciences Discussion HIV K65R 50 54 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. A notable exception to this are mutations located in G190 position: G190S and G190A both have reduced replication efficiency relative to wild-type and K103N-mutants. 2021 Revista espanola de quimioterapia Discussion HIV G190A;G190S;K103N 78;68;151 83;73;156 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Considering NRTI-RAMS, we found high representation and mutational viral load for M41L and T215I, associated to resistance to thymidine analogs. 2021 Revista espanola de quimioterapia Discussion HIV M41L;T215I 82;91 86;96 NRTI 12 16 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. K103N, most frequent NNRTI RAM, has a fitness similar to wild-type virus, a property that justifies its predominance within viral quasispecies population. 2021 Revista espanola de quimioterapia Discussion HIV K103N 0 5 NNRTI 21 26 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. M184I/V was infrequent in naive pregnant women. 2021 Revista espanola de quimioterapia Discussion HIV M184I;M184V 0;0 7;7 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Regarding overall prevalence of transmitted drug resistance, RAMs to NNRTI were predominant (mostly K103N) as in our original study and most Latin American reports. 2021 Revista espanola de quimioterapia Discussion HIV K103N 100 105 NNRTI 69 74 34085506 Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina. Therefore, updated local studies evaluating prevalence of M184I/V mutations in general population are needed. 2021 Revista espanola de quimioterapia Discussion HIV M184I;M184V 58;58 65;65 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. As expected the most common NRTI DRMs were thymidine analog mutations, namely M41L, D67N, T215S/V, K219Q, associated with high levels of resistance to zidovudine, but also affect the abacavir and tenofovir sensitivity. 2021 Scientific reports Discussion HIV D67N;K219Q;M41L;T215S;T215V 84;99;78;90;90 88;104;82;97;97 NRTI 28 32 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. Furthermore, L74I polymorphism was almost invariably (94.1%) present in A6 sequences. 2021 Scientific reports Discussion HIV L74I 13 17 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. In one sequence the NNRTI non-polymorphic E138K mutation, associated with reduced RPV susceptibility, was found. 2021 Scientific reports Discussion HIV E138K 42 47 NNRTI 20 25 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. In the integrase region, the most common (9.8%) polymorphism was E157Q, which is usually selected in patients receiving raltegravir or elvitegravir, but not associated with significant effect on the integrase treatment efficacy. 2021 Scientific reports Discussion HIV E157Q 65 70 IN;IN 7;199 16;208 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. Moreover, there is an emerging signal for the transmission of the non-polymorphic integrase mutation (E138K), previously not observed in the country. 2021 Scientific reports Discussion HIV E138K 102 107 IN 82 91 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. On the other hand, frequency of the V106I variant, which may be affecting doravirine susceptibility was higher (4.4%) than in reference data (0.8%) from Italy and France published by Soulie et al. 2021 Scientific reports Discussion HIV V106I 36 41 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. The remining observed NNRTI DRMs were accessory, potentially reducing susceptibility to etravirine or rilpivirine (E138A). 2021 Scientific reports Discussion HIV E138A 115 120 NNRTI 22 27 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. This variant may reduce integrase susceptibility if present in combination with other DRMs within this region, especially R263K. 2021 Scientific reports Discussion HIV R263K 122 127 IN 24 33 34140600 Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. We have previously observed the similar frequency (5.3%) of the rilpivirine associated DRMs with E138A and E138G being the most common DRM. 2021 Scientific reports Discussion HIV E138A;E138G 97;107 102;112 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. However, a recent 2020 case report did document treatment-emergent resistance in a treatment-experienced individual who had received crushed BIC/FTC/TAF tablets through a nasogastric tube, which the authors speculate may have resulted in inadequate blood levels of the drug that led to the R263K mutation. 2021 Open forum infectious diseases Discussion HIV R263K 290 295 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. In treatment-naive individuals, the R263K (INI) mutation is very rare and has most commonly been observed by ultra-deep sequencing. 2021 Open forum infectious diseases Discussion HIV R263K 36 41 IN 43 46 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. Most cases of treatment failure with development of R263K (INI) mutations have been documented in the context of DTG administration, with failure most often linked to low serum drug levels from drug-drug interactions with rifampin or rifabutin. 2021 Open forum infectious diseases Discussion HIV R263K 52 57 IN 59 62 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. Neither the M184V (RT) mutation nor the R263KR (INI) mutation was observed in the 2 pretreatment genotypes, suggesting that these were treatment-emergent mutations and were not transmitted or present at baseline. 2021 Open forum infectious diseases Discussion HIV M184V;R263K;R263R 12;40;40 17;46;46 IN;RT 48;19 51;21 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. One mutation of particular interest is the R263K (INI) mutation, which confers low-level (<3-fold reduced susceptibility) resistance to DTG and BIC and is associated with diminished HIV DNA integration and viral fitness. 2021 Open forum infectious diseases Discussion HIV R263K 43 48 IN 50 53 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. Prior to treatment initiation, he had 2 genotypes with integrase testing performed: one at diagnosis revealing a wild-type virus and the other 4 weeks later revealing an L74I (RT) mutation. 2021 Open forum infectious diseases Discussion HIV L74I 170 174 IN;RT 55;176 64;178 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. Resistance to RAL and EVG has been well-characterized in the literature with the accumulation of primary resistance substitutions along several pathways including the N155H, Q148, and G140A/G148R/H/Q pathways conferring high-level cross-resistance to RAL and EVG. 2021 Open forum infectious diseases Discussion HIV G140A;G148H;G148Q;G148R;N155H 184;190;190;190;167 189;199;199;199;172 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. The M184V (RT) mutation was detected after 17 weeks of therapy, and at week 37 the R263KR (INI) mutation was detected via bulk sequencing (Viracor Lab, Missouri) necessitating a change in ART. 2021 Open forum infectious diseases Discussion HIV M184V;R263K;R263R 4;83;83 9;89;89 IN;RT 91;11 94;13 34189182 Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy. Two other reported cases of the R263KR (INI) mutation have been in individuals with non-subtype B HIV type 1, both with advanced HIV disease, one in a treatment-experienced individual and another under first-line treatment with BIC/FTC/TAF. 2021 Open forum infectious diseases Discussion HIV R263K;R263R 32;32 38;38 IN 40 43 HIV diseases 129 140 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. As a result, parental IN_a and RAL resistant IN variants with D64V mutation were equally potent in inducing IFN-gamma/IL-2 production by splenocytes of mice stimulated with IN-derived peptides. 2021 Microorganisms Discussion HIV D64V 62 66 IN;IN 45;173 47;175 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Hence, we modified both enzymes introducing inactivating mutation D64V, and proved the loss of 3'-processing and strand transfer activities, making IN variants safe to use as DNA immunogens. 2021 Microorganisms Discussion HIV D64V 66 70 IN 148 150 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Interestingly, incorporation of the inactivation mutation D64V partially reversed both effects, restoring IN sensitivity to proteasome and inhibiting its sensitivity to lysosome. 2021 Microorganisms Discussion HIV D64V 58 62 IN 106 108 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Introduction of inactivation mutation D64V led to a decrease in peptide-specific cytokine production, and shrinkage of the spectrum of recognized epitopes compared to that induced by enzymatically active IN variant, although the epitopes above were not directly affected by the mutation. 2021 Microorganisms Discussion HIV D64V 38 42 IN 204 206 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Of note, IN_in_r2 DNA-immunized mice received a challenge with 4T1luc2 cells expressing IN identical to the immunogen with the exception of D64V mutation. 2021 Microorganisms Discussion HIV D64V 140 144 IN 88 90 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. Since IN_in_r2 mice exhibited low level of resistance to tumor growth, despite a match between IN immunogen and IN expressed by tumor cells (except for D64V mutation), this type of response was apparently unfavorable. 2021 Microorganisms Discussion HIV D64V 152 156 IN;IN 95;112 97;114 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. The loss of immunogenicity due to D64V mutation was restored by introduction of RAL resistance mutation patterns; RAL resistant IN variants were equally immunogenic. 2021 Microorganisms Discussion HIV D64V 34 38 IN 128 130 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. We could not obtain 4T1luc2 cells expressing IN_in_r1; hence, IN_in_r1 DNA-immunized mice were challenged with 4T1luc2 cells expressing IN_a, different from the immunogen in six amino acid residues, of which one, E92Q, was localized in the T cell epitope at aa 79-98 recognized by IN-immunized mice (Figure 9). 2021 Microorganisms Discussion HIV E92Q 213 217 IN 281 283 34199989 Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells. We synthesized an expression optimized gene encoding consensus integrase (IN) of HIV-1 clade A, and using it as a platform, two drug resistant variants with alternative patterns of resistance to raltegravir combining primary and early occurring secondary/adaptive mutations L74M/E92Q/V151I/N155H/G163R (IN_r1_in) or E138K/G140S/Q148K (IN_r2_in). 2021 Microorganisms Discussion HIV E138K;E92Q;G140S;G163R;L74M;N155H;Q148K;V151I 316;279;322;296;274;290;328;284 321;283;327;301;278;295;333;289 IN;IN 63;74 72;76 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. An elevated frequency of M184V (75%) was also detected herein, as well as in the study conducted in Belem; this has ranged from 54.4% in Sao Paulo to 81.2% in Bahia. 2021 BioMed research international Discussion HIV M184V 25 30 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. Despite the low impact of the M184V alone to NRTI resistance, when taken together to other NRTI DRM, an increased level of resistance could be verified as shown in this study and in others. 2021 BioMed research international Discussion HIV M184V 30 35 NRTI;NRTI 45;91 49;95 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. Due to the presence of mutations, such as L100I, K101P, Y181C, M230L, observed in of individuals failing in the use of EFV, the viability of using ETR in a rescue scheme is reduced for few individuals (data not shown). 2021 BioMed research international Discussion HIV K101P;L100I;M230L;Y181C 49;42;63;56 54;47;68;61 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. The increase of NNRTI resistance is mainly correlated to the presence of the K103N mutation, which was detected in 71.8% of individuals that use NNRTI, as also previously described. 2021 BioMed research international Discussion HIV K103N 77 82 NNRTI;NNRTI 16;145 21;150 34212033 High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil. The prevalence of K103N/S in our study (63.4%) was higher than the mean of 40% detected for the five largest Brazilian cities (Sao Paulo, Rio de Janeiro, Espirito Santo-Southeast region and Bahia and Ceara-Northeast region) and also in Belem, another city in the northern region. 2021 BioMed research international Discussion HIV K103N;K103S 18;18 25;25 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. Animal models have shown that oral TDF/FTC did not reliably prevent infection with HIV strains with K65R. 2021 BMC infectious diseases Discussion HIV K65R 100 104 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. It is no surprise that NNRTI-related mutations increased rapidly in China recently, and M184V/I and T215I/Y/S/D/F were the main NRTI DRMs in ART-naive and ART-treated individuals, respectively. 2021 BMC infectious diseases Discussion HIV M184I;M184V;T215D;T215F;T215I;T215S;T215Y 88;88;100;100;100;100;100 95;95;113;113;113;113;113 NNRTI;NRTI 23;128 28;132 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. K65R and M184I/V were both listed in the common DRMs to TDR and ADR and were believed to be induced under the pressure of TDF and 3TC. 2021 BMC infectious diseases Discussion HIV M184I;M184V;K65R 9;9;0 16;16;4 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. Phylogenetic analysis indicated that most TDR strain transmission was sporadic, except for two K65R carrying CRF01_AE strains with very close genetic distance. 2021 BMC infectious diseases Discussion HIV K65R 95 99 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. We found three DRMs (K65R, M184I/V, and Y115Y/F) that caused resistance to TDF/FTC. 2021 BMC infectious diseases Discussion HIV K65R;M184I;M184V;Y115F;Y115Y 21;27;27;40;40 25;34;34;47;47 34243716 Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018. Y115Y/F was not a common DRM and could be selected by ABC and TDF, both of which were free ART drugs in China and confer high-level resistance to ABC and low-level resistance to TDF. 2021 BMC infectious diseases Discussion HIV Y115F;Y115Y 0;0 7;7 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. Mutations K65R, Y181C+G190S, which produced high drug resistance, did not enter the transmission network. 2021 Medicine Discussion HIV G190S;K65R;Y181C 22;10;16 27;14;21 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. The L33F mutation constitutes interconnection in the largest spreading cluster in the network. 2021 Medicine Discussion HIV L33F 4 8 34260561 HIV-1 molecular transmission network among sexually transmitted populations in Liaoning Province, China. Two of them were CRF01_AE subtype, resistance gene is protease inhibitor-related resistance, mutation site is L33F, Q58E. 2021 Medicine Discussion HIV L33F;Q58E 110;116 114;120 PR 54 62 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Interestingly, when we continued the culture of the cloned Y99H mutant virus for additional three passages in the presence and absence of STP0404 (12 nM), we still did not observe any additional mutations in the cloned IN genes. 2021 PLoS pathogens Discussion HIV Y99H 59 63 IN 219 221 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. It is interesting, however, that while the A128T IN mutant virus replicated similarly to the wild type, the Y99H IN mutant as well as Y99H/A128T virus displayed severely defective replication capability, implying the unfit nature of STP0404 resistance viruses. 2021 PLoS pathogens Discussion HIV A128T;A128T;Y99H;Y99H 43;139;108;134 48;144;112;138 IN;IN 49;113 51;115 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Note that in two independent STP0404 resistance selection experiments (Fig 2), Y99H was selected first at comparatively low STP0404 concentration, while A128T was subsequently acquired to confer full resistance against STP0404. 2021 PLoS pathogens Discussion HIV A128T;Y99H 153;79 158;83 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Possibly, the Y99H mutation may induce a conformational change near the STP0404 binding site that assists the molecular clash between the substituted T128 residue and STP0404. 2021 PLoS pathogens Discussion HIV Y99H 14 18 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. The Y99H mutation has been much less commonly reported compared to other known ALLINI resistance mutations such as A128T. 2021 PLoS pathogens Discussion HIV A128T;Y99H 115;4 120;8 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. Therefore, the putative conformational change made by Y99H appears to be sufficient to block compound binding at low STP0404 concentrations. 2021 PLoS pathogens Discussion HIV Y99H 54 58 34293041 A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. This suggests the Y99H mutant did not improve its unfit phenotype by gaining any compensatory IN mutations during these three passages regardless of the STP0404 treatment. 2021 PLoS pathogens Discussion HIV Y99H 18 22 IN 94 96 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. As expected, no major INIs RAMs were detected, and only a minor mutation, T97A, was detected in 3 patients, one of whom subsequently experienced VF. 2021 Open forum infectious diseases Discussion HIV T97A 74 78 IN 22 26 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Because no impact on failure of first-generation INI has been reported, a causal relationship of T97A alone on VF is debatable. 2021 Open forum infectious diseases Discussion HIV T97A 97 101 IN 49 52 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. However, previous observational studies suggested an increased risk of VF during 3TC-based DT when M184V/I was present in combination with a shorter time of viral suppression. 2021 Open forum infectious diseases Discussion HIV M184I;M184V 99;99 106;106 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Indeed, M184V/I and TAMs appear to synergize with each other since TAMs alone were not associated with VF. 2021 Open forum infectious diseases Discussion HIV M184I;M184V 8;8 15;15 34327247 Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice. Our study showed that a shorter duration of virological suppression and the presence of M184V/I were independent predictors of VF; however, M184V/I alone was less accurate in predicting the outcome than its combination with TAMs. 2021 Open forum infectious diseases Discussion HIV M184I;M184I;M184V;M184V 88;140;88;140 95;147;95;147 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. A high frequency of K65R plus M184V/I (15.0%) was observed in this study, and K65R plus M184 V/I appeared sufficient to abrogate the NRTI activity of a regimen comprising ABC, TDF or D4T. 2021 Infection and drug resistance Discussion HIV K65R;K65R;M184I;M184I;M184V;M184V 20;78;30;88;30;88 24;82;37;96;37;96 NRTI 133 137 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. In contrast, M184I/V increased susceptibility to Zidovudine (AZT), Stavudine (D4T) and TDF and slowed the emergence of AZT, D4T, and TDF resistance. 2021 Infection and drug resistance Discussion HIV M184I;M184V 13;13 20;20 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. In our study, V179E/D was the most common NNRTI-associated mutation, accounting for 37.9%. 2021 Infection and drug resistance Discussion HIV V179D;V179E 14;14 21;21 NNRTI 42 47 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. K65R (27.2%) is the second most common NRTI-associated resistance mutation and has only a relatively low level of reduced drug susceptibility. 2021 Infection and drug resistance Discussion HIV K65R 0 4 NRTI 39 43 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. M184I/V (42.2%) was the most prevalent NRTI-associated mutation, which might be caused by the frequent use of 3TC in ART-experienced patients. 2021 Infection and drug resistance Discussion HIV M184I;M184V 0;0 7;7 NRTI 39 43 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V106I/M, K103N/Q, G190A/S, and Y181C were the major NNRTI-associated mutations, similar to those in other cities in China and other countries, and showed broad-spectrum resistance possibly caused by the wide use of NNRTIs. 2021 Infection and drug resistance Discussion HIV G190A;G190S;K103N;K103Q;V106I;V106M;Y181C 18;18;9;9;0;0;31 25;25;16;16;7;7;36 NNRTI;NNRTI 52;215 57;221 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V179D reduces NVP and EFV susceptibility by 2- to 5-fold and reduces ETR and RPV susceptibility by 2- to 3-fold, respectively. 2021 Infection and drug resistance Discussion HIV V179D 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V179E is a nonpolymorphic mutation weakly selected by NVP and EFV. 2021 Infection and drug resistance Discussion HIV V179E 0 5 34377002 HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019. V179E/D does not appear to reduce the virological response to a first-line EFV-containing regimen. 2021 Infection and drug resistance Discussion HIV V179D;V179E 0;0 7;7 34397746 Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. Pre-existing NRTI resistance, including the M184V/I mutation, did not impact the efficacy of switching to B/F/TAF. 2021 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184I;M184V 44;44 51;51 NRTI 13 17 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Alternatively, a very recent report has demonstrated that addition of the T371I substitution can rescue IP6 incorporation in HIV-1K359A virions to near WT levels. 2021 Retrovirology Discussion HIV T371I 74 79 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Alternatively, the lack of impairment of HIV-1T371I or HIV-1K359A/T371I in the setting of reduced cellular IP6 levels maybe be due to the T371I substitution itself increasing affinity of the lattice for IP6, thus rendering virions less responsive to a reduction in cellular IP6 levels. 2021 Retrovirology Discussion HIV T371I;T371I 66;138 71;143 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Because the T371I substitution apparently mimics the effect of MIs, we hypothesized that MIs might also rescue the infectivity of HIV-1K359A. 2021 Retrovirology Discussion HIV T371I 12 17 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Conversely, manipulations such as the T371I substitution or treatment of HIV-1WT with BVM, hyper-stabilize the immature lattice in the wild type context and decrease HIV-1 infectivity. 2021 Retrovirology Discussion HIV T371I 38 43 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Despite several attempts we were unable to generate revertant mutants for HIV-1K290A and HIV-1R18A (although follow-up studies demonstrated that the T371I substitution rescues HIV-1K290A as well as HIV-1K359A). 2021 Retrovirology Discussion HIV T371I 149 154 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Here, we report the identification of a single amino acid substitution (T371I) that rescues the replication of the defective, IP6-binding deficient mutant HIV-1K359A. 2021 Retrovirology Discussion HIV T371I 72 77 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. HIV-1K359A/T371I was fully infectious despite containing a mutation (K359A) that renders VLP assembly unresponsive to IP6 in vitro and which substantially impairs IP6 incorporation into virions. 2021 Retrovirology Discussion HIV K359A;T371I 69;11 74;16 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. However, either the T371I substitution or BVM treatment are able to rescue virion assembly and infectiousness in the context of IP6 deficiency. 2021 Retrovirology Discussion HIV T371I 20 25 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. However, we also found no difference in the infectiousness of HIV-1K359A/T371I in WT and IPMK KO MT4 target cells. 2021 Retrovirology Discussion HIV T371I 73 78 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Indeed, we found no significant reduction in yield of HIV-1K359A/T371I from IPMK KO 293T cells, in contrast to WT HIV-1. 2021 Retrovirology Discussion HIV T371I 65 70 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Indeed, while production of HIV-1WT was impaired in IPMK KO cells, there was no impairment of HIV-1T371I or HIV-1K359A/T371I in these cells. 2021 Retrovirology Discussion HIV T371I;T371I 99;119 104;124 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Nevertheless, our data utilizing genetic ablation of the IP6 synthetic machinery suggests that the T371I substitution confers reduced dependence on cellular inositol phosphate levels for virion assembly. 2021 Retrovirology Discussion HIV T371I 99 104 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. That the stabilizing effects of both the T371I substitution and BVM can compensate for the lack of IP6 coordination in HIV-1K359A provides in vivo mechanistic support for the model proposed by Dick et al.: i.e. 2021 Retrovirology Discussion HIV T371I 41 46 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. The T371I substitution, identified herein as a compensatory mutation that rescues infectivity deficit found in HIV-1K359A, has previously been reported to rescue the infectivity of virions containing substitutions that confer resistance to maturation inhibitors (MIs). 2021 Retrovirology Discussion HIV T371I 4 9 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. These substitutions render HIV-1 assembly-defective in the absence of MIs and the T371I substitution was shown to stabilize the CA-SP1 lattice in this context, effectively mimicking the action of MIs. 2021 Retrovirology Discussion HIV T371I 82 87 SP1;Capsid 131;128 134;130 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. This finding suggests that HIV-1K359A/T371I is no longer dependent on IP6 or requires substantially lower concentrations of IP6 in virus producing cells. 2021 Retrovirology Discussion HIV K359A;T371I 32;38 37;43 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. This notion is consistent with the recent report by Mallery et al., demonstrating that the T371I substitution rescues incorporation of IP6 in HIV-1K359A. 2021 Retrovirology Discussion HIV T371I 91 96 34454514 Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency. Thus HIV-1T371I and HIV-1K359A/T371I retains infectiousness even in the setting of reduced cellular IP6 levels, implying at least some level of IP6 independence, even if IP6 is incorporated into virions in the context of the HIV-1K359A/T371I double mutant. 2021 Retrovirology Discussion HIV T371I;T371I;T371I 10;31;236 15;36;241 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. A second DRM common in the outbreak sequences was the RT:K219N mutation, a thymidine analogue mutation associated with potential low-level resistance against zidovudine. 2021 Frontiers in microbiology Discussion HIV K219N 57 62 RT 54 56 34484134 Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan. The most prevalence DRM identified among both ART-experienced and ART-naive individuals was RT:E138A which confers a high-level resistance to NNRTIs such as Rilpivirine. 2021 Frontiers in microbiology Discussion HIV E138A 95 100 NNRTI;RT 142;92 148;94 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. A cluster (cluster C) containing HIV strains sharing the same SDRM (K103N) was found in the present study. 2021 Virology journal Discussion HIV K103N 68 73 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. The most frequent NNRTI-associated SDRM in our study was K103N, while it is V179E and V106I in Southwest China and K103N/S and E138A in Iceland and the south-central United States. 2021 Virology journal Discussion HIV E138A;K103N;K103N;K103S;V106I;V179E 127;57;115;115;86;76 132;62;122;122;91;81 NNRTI 18 23 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. The most frequent NRTI-associated mutations in our study were M184V and L210W, while they are M41L and D67G in Southwest China and T215C/D in Iceland and the south-central United States. 2021 Virology journal Discussion HIV D67G;L210W;M184V;M41L;T215C;T215D 103;72;62;94;131;131 107;77;67;98;138;138 NRTI 18 22 34488793 Transmitted drug resistance and transmission clusters among HIV-1 treatment-naive patients in Guangdong, China: a cross-sectional study. The most frequent PI-associated mutation in our study was M46L, whereas it is Q56E in southwest China, M46I in Iceland, and L90M in the south-central United States. 2021 Virology journal Discussion HIV L90M;M46I;M46L;Q56E 124;103;58;78 128;107;62;82 PI 18 20 34534138 Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection. In these larger, fully powered, randomized GEMINI-1 and GEMINI-2 studies, 1 participant with transiently increased HIV-1 RNA levels late in the study period (week 132; did not meet CVW criteria) developed the M184V and R263R/K mutations. 2022 AIDS (London, England) Discussion HIV M184V;R263K;R263R 209;219;219 214;226;226 34534138 Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection. Notably, in the single-group, phase II pilot study ACTG A5353 assessing DTG + 3TC in treatment-naive participants with HIV-1, three participants met virologic failure criteria, one of whom developed M184V and R263R/K mutations. 2022 AIDS (London, England) Discussion HIV M184V;R263K;R263R 199;209;209 204;216;216 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. 2-LTR circles are considered a surrogate for nuclear entry, and as A14C/E45C and E180C produced 2-LTR circles in 293T cells, HeLa cells and cycling U937 cells, albeit with a 5-10 fold decrease compared to WT (Fig 5), it suggested that at least a proportion of particles could enter the nucleus. 2021 PLoS pathogens Discussion HIV A14C;E180C;E45C 67;81;72 71;86;76 LTR;LTR 2;98 5;101 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. As equal numbers of cores were arriving at the nucleus (as measured by NUP358 co-localisation), this suggests that the A14C/E45C cores were spending more time at the nuclear pore. 2021 PLoS pathogens Discussion HIV A14C;E45C 119;124 123;128 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. As seen in a previous report, we observed some CA-NUP358 foci in the cytoplasm, which was more noticeable during A14C/E45C infection. 2021 PLoS pathogens Discussion HIV A14C;E45C 113;118 117;122 Capsid 47 49 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. As WT CA was barely detectable in the chromatin fraction (Fig 6E and S3G Fig), this could reflect WT cores being able to breakdown and deliver IN more efficiently to the chromatin than A14C/E45C cores which appear to retain some CA in the chromatin fraction (Figs 6E and S3G). 2021 PLoS pathogens Discussion HIV A14C;E45C 185;190 189;194 IN;Capsid;Capsid 143;6;229 145;8;231 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Furthermore, unlike WT HIV-1, neither the N74D nor the A77V mutant can re-localise CPSF6 to nuclear speckles, showing that this is a CA dependent event. 2021 PLoS pathogens Discussion HIV A77V;N74D 55;42 59;46 Capsid 133 135 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Importantly, A14C/E45C is still able to bind CPSF6 in vitro, suggesting that either it does not have access to CPSF6 in cells, or that it is unable to relocate to nuclear speckles because it is retained elsewhere. 2021 PLoS pathogens Discussion HIV A14C;E45C 13;18 17;22 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Interestingly, studies with the CPSF6 binding-defective HIV-1 CA mutants, N74D and A77V, have reported that a longer residence time at the nuclear envelope promotes integration into heterochromatin regions close to the nuclear envelope. 2021 PLoS pathogens Discussion HIV A77V;N74D 83;74 87;78 Env;Env;Capsid 147;227;62 155;235;64 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. It has also been reported that the hyper-stable E45A CA mutant can still partially open. 2021 PLoS pathogens Discussion HIV E45A 48 52 Capsid 53 55 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. It is interesting to recall that the A14C/E45C mutant still produces 2-LTR circles, despite apparent limited nuclear entry, questioning what this product really represents. 2021 PLoS pathogens Discussion HIV A14C;E45C 37;42 41;46 LTR 71 74 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. It is intriguing that the NTD-NTD mutant A14C/E45C resulted in hyper-stable cores whilst the NTD-NTD mutant A42C/T54C did not, as they have near identical hexamer crystal structures. 2021 PLoS pathogens Discussion HIV A14C;A42C;E45C;T54C 41;108;46;113 45;112;50;117 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Moreover, the A14C/E45C foci appeared to localise more towards the cytoplasmic side of the DAPI edge while the WT foci were mainly on the nuclear side, suggesting that WT cores travel further into the nucleus and that A14C/E45C hyper-stable cores are trapped at the NPC. 2021 PLoS pathogens Discussion HIV A14C;A14C;E45C;E45C 14;218;19;223 18;222;23;227 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Nevertheless, we found that two previously described intra-hexamer mutants, A14C/E45C and M68C/E212C, and a novel inter-hexamer mutant, E180C, all showed increased lattice stability in cells (Figs 2A, 2C and 6) and maintained disulphide bonds following infection (Figs 5A, 6D and 6F). 2021 PLoS pathogens Discussion HIV A14C;E180C;E212C;E45C;M68C 76;136;95;81;90 80;141;100;85;94 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Nonetheless, hyper-stability can be detrimental for reverse transcription as the M68C/E212C mutant showed a ~10-fold decrease in reverse transcription products compared to WT in all the cells lines studied (Figs 4D and 5). 2021 PLoS pathogens Discussion HIV E212C;M68C 86;81 91;85 RT;RT 52;129 73;150 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Since A14C/E45C cores were stalled at the nuclear pore, we were intrigued to see whether this mutant would be able to promote CPSF6 redistribution to nuclear speckles. 2021 PLoS pathogens Discussion HIV A14C;E45C 6;11 10;15 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Surprisingly, despite uncoating previously being linked to reverse transcription, A14C/E45C and E180C were able to reverse transcribe close to WT levels in 293T, HeLa and cycling U937 cells and, furthermore, showed only a partial reduction in 2-LTR circle production in these cells (Figs 4 and 5). 2021 PLoS pathogens Discussion HIV A14C;E180C;E45C 82;96;87 86;101;91 RT;LTR 59;245 80;248 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The cysteine residues introduced in M68C/E212C are located on the intra-hexamer NTD-CTD interface, which is important for the curvature of the lattice. 2021 PLoS pathogens Discussion HIV E212C;M68C 41;36 46;40 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. The increased CA levels in each fraction following infection with the A14C/E45C mutant suggest that there is more CA present per particle, presumably reflecting the increase in core stability. 2021 PLoS pathogens Discussion HIV A14C;E45C 70;75 74;79 Capsid;Capsid 14;114 16;116 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. There were significantly increased numbers of foci for the A14C/E45C CA at all time points. 2021 PLoS pathogens Discussion HIV A14C;E45C 59;64 63;68 Capsid 69 71 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. These results are in line with previous studies showing that hyper-stable mutants E45A, Q63A/Q67A, 5Mut (Q67H/K70R/H87P/T107N/L111) and A14C/E45C can reverse transcribe and with a recent report saying that reverse transcription can complete in whole WT cores. 2021 PLoS pathogens Discussion HIV H87P;K70R;Q67H;T107N;A14C;E45A;E45C;Q63A;Q67A 115;110;105;120;136;82;141;88;93 119;114;109;125;140;86;145;92;97 RT 206 227 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. Thus, we speculate that if A14C/E45C is still binding NUP153 at the nuclear pore, it might not be able to uncouple and move on to binding CPSF6. 2021 PLoS pathogens Discussion HIV A14C;E45C 27;32 31;36 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. To explore whether hyper-stable cores could truly enter the nucleus or were associating with nuclear membranes, we studied the dynamics of WT and A14C/E45C CA interactions with nuclear pore proteins (Fig 7). 2021 PLoS pathogens Discussion HIV A14C;E45C 146;151 150;155 Capsid 156 158 34543344 HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration. We found that WT and A14C/E45C CA showed similar levels of interaction with NUP358 over time (Fig 7B) suggesting that both cores could reach the nuclear pore with equivalent kinetics, agreeing with our fractionation experiments. 2021 PLoS pathogens Discussion HIV A14C;E45C 21;26 25;30 Capsid 31 33 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. Furthermore, it is worth noting that the DRM V179D/E associated with NNRTI was the most common, and spread widely within networks. 2021 Frontiers in genetics Discussion HIV V179D;V179E 45;45 52;52 NNRTI 69 74 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. Here, we found that sequences with V179D/E were distributed and networked among HETs, suggesting that V179D/E is involved in ongoing HIV-1 transmission in this region. 2021 Frontiers in genetics Discussion HIV V179D;V179D;V179E;V179E 35;102;35;102 42;109;42;109 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. Sharing of specific DRMs (such as V106I and V179D/E) was frequent within networks, revealing the potential for widespread PDR dissemination in the future. 2021 Frontiers in genetics Discussion HIV V106I;V179D;V179E 34;44;44 39;51;51 34567064 Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China. Studies have reported that V179D/E has been on the rise among the MSM population in recent years. 2021 Frontiers in genetics Discussion HIV V179D;V179E 27;27 34;34 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. Despite this, we found several polymorphic accessory INSTI-selected mutations (e.g., T97A and E157Q) in eight children/adolescents and four pregnant women associated with low-level drug resistance. 2021 Genes Discussion HIV E157Q;T97A 94;85 99;89 INSTI 53 58 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. In contrast, M184V induces hypersusceptibility to TDF and AZT, while simultaneously limiting the emergence of drug resistance to both agents. 2021 Genes Discussion HIV M184V 13 18 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. It is plausible that while adherence may have been low in both groups, it was comparatively much lower among pregnant women, resulting in less pharmacologic pressure in this group and increasing the reversion rate of M184V-selected viruses to WT viruses. 2021 Genes Discussion HIV M184V 217 222 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. Studies have shown that M184V is associated with reduced replicative activity in the absence of drug pressure, compared with the wild-type (WT) virus. 2021 Genes Discussion HIV M184V 24 29 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. The children and adolescents were all (100%) ART-experienced for a much longer duration (median of 48 months) compared with the pregnant women (72.2% ART-experienced for a median duration of 3 months) and would, therefore, be expected to accumulate more M184V viruses, due to the overall higher drug exposure. 2021 Genes Discussion HIV M184V 254 259 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. The marked disparity in frequency of M184V-selected viruses among children and adolescents (77%) and pregnant women (11%) was noteworthy. 2021 Genes Discussion HIV M184V 37 42 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. The prevalence of the NNRTI mutation K103N, which is selected by EFV and NVP was high in all three study groups. 2021 Genes Discussion HIV K103N 37 42 NNRTI 22 27 34573296 Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone. We found that M184V was the most frequent NRTI RAM, occurring with a prevalence of nearly 77% among children/adolescents and 11% of pregnant women. 2021 Genes Discussion HIV M184V 14 19 NRTI 42 46 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Although the Y712A mutant may package Env less efficiently, the higher levels of surface Env may enhance the level of Env engagement by target cells, in a manner that is independent of recycling pathways that enhance Env incorporation. 2021 Viruses Discussion HIV Y712A 13 18 Env;Env;Env;Env 38;89;118;217 41;92;121;220 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. However, in the case of the Y712A mutant, we observed significantly higher levels of Env transferred into target cells (Figure 4C,D). 2021 Viruses Discussion HIV Y712A 28 33 Env 85 88 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In cell-cell transfer experiments, we observed a small but significant decrease in the efficiency of Gag transferred into target cells using donor cells infected with viruses carrying the Y712A and LL855AA mutations (Figure 4C,D). 2021 Viruses Discussion HIV Y712A 188 193 Gag 101 104 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In infected target cells, the co-localization of Env and Gag was lower in target cells co-cultured with Y712A-infected cells vs. 2021 Viruses Discussion HIV Y712A 104 109 Env;Gag 49;57 52;60 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. In visualizing the localization of Env and Gag in cells engaged in VSs, we observed a higher ratio of Env- to Gag-associated fluorescence accumulating at VSs when using Y712A-infected donor cells, as compared to WT-infected cells. 2021 Viruses Discussion HIV Y712A 169 174 Env;Env;Gag;Gag 35;102;43;110 38;105;46;113 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Previous studies have shown that the Env Y712A motif mutations enhanced surface Env expression yet reduced the levels of Env incorporated into virus particles, thus lowering viral particle infectivity. 2021 Viruses Discussion HIV Y712A 41 46 Env;Env;Env 37;80;121 40;83;124 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. The increase in the Env-to-Gag ratio transferred into target cells after cell-cell HIV transfer with Y712A-infected cells correlated with a 2-fold decrease in productive infection as compared to the WT (Figure 4E,F). 2021 Viruses Discussion HIV Y712A 101 106 Env;Gag 20;27 23;30 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. The pronounced increase in surface Env expression was observed in the HIV Y712A Env-infected cells, which was around 6-fold higher than either WT- or 855-infected cells (Figure 4). 2021 Viruses Discussion HIV Y712A 74 79 Env;Env 35;80 38;83 34578310 Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission. Therefore, the increased Env at VSs in Y712A-infected cells may be attributable to the level of Env accumulated on the surface of these cells prior to engaging in cell-cell conjugates. 2021 Viruses Discussion HIV Y712A 39 44 Env;Env 25;96 28;99 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. M184 V and K65R together are sufficient to inhibit the activity of a TDF and ABC-containing regimen while also increasing sensitivity to AZT. 2021 Medicine Discussion HIV K65R;M184V 11;0 15;6 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. M184 V/I was the most common major NRTI resistance mutation. 2021 Medicine Discussion HIV M184V 0 8 NRTI 35 39 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. Similar M184 V/I predominance trends (81.2%) have been reported in Uganda. 2021 Medicine Discussion HIV M184I;M184V 8;8 16;16 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. The fact that 3TC is a backbone for most Kenyan ART-regimens explains this predominance of M184 V/I. 2021 Medicine Discussion HIV M184I;M184V 91;91 99;99 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. The high levels of resistance are due to the K103N, G190A, and Y181C mutations, which confer resistance to NVP (81.0%) and EFV (71.2%). 2021 Medicine Discussion HIV G190A;K103N;Y181C 52;45;63 57;50;68 34622871 Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study. The K65R mutation was found in 32 sequences on 3TC, ABC, and TDF regimens, increasing viral resistance to TDF and ABC by 2-fold and 3TC and FTC by 5 to 10-fold, respectively. 2021 Medicine Discussion HIV K65R 4 8 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. An important exception to the broad coverage of TMR is with CRF01_AE viruses, wherein envelopes routinely exhibited high IC50 values to TMR, owing to the regular presence of two key polymorphisms (S375H and M475I) in most CFR01_AE viruses. 2022 AIDS (London, England) Discussion HIV M475I;S375H 207;197 212;203 Env 86 95 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. However, it has been shown that for TMR, changes far away from the binding site, at L116P and A204D in the LAI envelope, can greatly reduce susceptibility to TMR, even if these changes have not been observed in the clinic and are extremely rare in the LANL database of envelope sequences. 2022 AIDS (London, England) Discussion HIV A204D;L116P 94;84 99;89 Env;Env 111;269 119;277 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Preexisting polymorphisms that affected TMR susceptibility were identified in three participants; one co-dosed with IBA (Individual 153 with M426L at Screening) and two with MVC (Individuals 203 and 474 with M426L and M434T at Screening, respectively). 2022 AIDS (London, England) Discussion HIV M426L;M426L;M434T 141;208;218 146;213;223 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. The lone envelope with a reduced IC50 to TMR contained the known M426L TMR polymorphism. 2022 AIDS (London, England) Discussion HIV M426L 65 70 Env 9 17 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. The M434T polymorphism is extremely rare, with 32 of 7561 (0.4%) full length envelopes in the Los Alamos National Laboratory (LANL) database of HIV sequences having this change, which results in a 15-fold drop in susceptibility when tested in an LAI envelope background. 2022 AIDS (London, England) Discussion HIV M434T 4 9 Env;Env 77;250 86;258 34628442 Clinical evidence for a lack of cross-resistance between temsavir and ibalizumab or maraviroc. Within the six participants (where data were available) who encountered PDVF when co-dosed with FTR and either IBA or MVC, five participants had emergent substitutions of S375H/N, M426L, or M475I, while Individual 153, with an M426L at Screening, had no TMR-specific emergent changes but did exhibit a relatively high but unchanged IC50 at Screening and PDVF. 2022 AIDS (London, England) Discussion HIV M426L;M426L;M475I;S375H;S375N 180;227;190;171;171 185;232;195;178;178 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. At the 80 mg dose level, UDS but not the chain-termination method detected K103N and V189I at <5% at 7 days postdose, although viral load showed continued decline at this timepoint. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV K103N;V189I 75;85 80;90 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. F227C is an NNRTI-resistance-associated variant that is clinically rare (<=0.5% of all clinical samples), observed primarily in patients receiving doravirine and less frequently in people receiving etravirine or rilpivirine. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C 0 5 NNRTI 12 17 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. F227C would not be expected to emerge in combination with an antiretroviral of another class with activity against F227C; the intended clinical use of MK-8507 is as part of a weekly combination therapy. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C;F227C 115;0 120;5 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. In a second participant without a viral rebound 14 days postdose, F227C was found as a minority variant using UDS. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C 66 71 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. No rebound was observed in the first 7 days postdose in this study, and detection of K103N at 7 days postdose in 1 participant and F227C in another at 14 days postdose were not accompanied by rebound. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C;K103N 131;85 136;90 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. Two NNRTI-resistance-associated variants (E138G and V179D) were detected in 1 participant each in the 600 mg panel before dosing, but were not detected postdose, indicating that MK-8507 did not select for these. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138G;V179D 42;52 48;57 NNRTI 4 9 34654041 Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. Viral rebound 14 days postdose was seen in 1 participant with F227C. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV F227C 62 67 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. According to our experiment, inhibition of HIV-1 replication by AnkGAG1D4-S45Y results in late detection of syncytium formation, followed by extended cell viability. 2021 Biomolecules Discussion HIV S45Y 74 78 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. According to previous work, substituting tyrosine for serine improves the binding affinity of Myr (+) AnkGAG1D4-S45Y without altering specificity. 2021 Biomolecules Discussion HIV S45Y 112 116 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. For example, the M184V mutation along with thymidine analogue-associated mutations (TAMs) in HIV-1 reverse transcriptase gene increases abacavir resistance. 2021 Biomolecules Discussion HIV M184V 17 22 RT 99 120 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. In this study, antiviral activity of Myr (+) AnkGAG1D4-S45Y was observed in infected SupT1 cells compared with parental Myr (+) AnkGAG1D4. 2021 Biomolecules Discussion HIV S45Y 55 59 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. Replacement with tyrosine provides more stable interaction of AnkGAG1D4-S45Y against viral targets, leading to higher efficiency in anti-viral activity. 2021 Biomolecules Discussion HIV S45Y 72 76 34680070 Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production. SupT1 cells expressing AnkGAG1D4 and AnkGAG1D4-S45Y were infected with HIV-1 NL4-3 MIRCAI201V virus. 2021 Biomolecules Discussion HIV S45Y 47 51 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Collectively, these 3 possible resistance mechanisms would result in a mechanistic bottleneck because the steric occupation of G118R in the catalytic site both prevents INSTI binding and hinders tDNA binding. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 127 132 INSTI 169 174 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Dolutegravir also selects for G118R or R263K in vitro, both alone and in combination with E138K. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;G118R;R263K 90;30;39 95;35;44 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Dolutegravir has selected for N155H, both alone and in combination with E138K and/or other integrase substitutions, in ART-experienced participants from several studies, including SAILING and multiple trials evaluating dolutegravir monotherapy. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;N155H 72;30 77;35 IN 91 100 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Dolutegravir retained prolonged binding to integrase-DNA complexes with G118R or R263K substitutions relative to other INSTIs, and the drug's resistance through this pathway could be rationalized at the HIV-1 integrase molecular level. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 72;81 77;86 IN;IN;INSTI 43;209;119 52;218;125 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Emergence of G118R and R263K has been documented in 1 case report of an individual receiving dolutegravir plus 2 NRTIs who was treated for tuberculosis and diagnosed with immune reconstitution inflammatory syndrome, but these DAWNING clonal analyses provide the first known demonstration that G118R can exist with R263K on the same HIV-1 genome. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;G118R;R263K;R263K 13;293;23;314 18;298;28;319 NRTI 113 118 Tuberculosis 139 151 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Finally, G118R stabilizes the product tDNA by forming a direct hydrogen bond with the 3' hydroxy of the tDNA terminal thymine after final formation of the vDNA/tDNA substrate complex. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 9 14 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. For drugs with a lower barrier, effective resistance can be achieved with a single mutation while maintaining viral fitness; for example, efavirenz resistance can occur via the single reverse transcriptase substitution K103N. 2022 Antimicrobial agents and chemotherapy Discussion HIV K103N 219 224 RT 184 205 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G118R alone had a greater impact on increasing dolutegravir resistance and reducing replication capacity compared with G118R plus other integrase substitutions. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;G118R 119;0 124;5 IN 136 145 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G118R can prevent dolutegravir and other INSTIs from binding effectively by sterically occupying and partially occluding the integrase catalytic binding site, which is supported by our kinetic binding studies. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 0 5 IN;INSTI 125;41 134;47 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G118R emerged in combination with >=3 other integrase substitutions in 3 participants, including with R263R/K plus E138E/K in 2 participants. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138E;E138K;R263K;R263R;G118R 115;115;102;102;0 122;122;109;109;5 IN 44 53 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. G118R has also emerged without other integrase substitutions in ART-experienced individuals receiving dolutegravir monotherapy. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 0 5 IN 37 46 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. HIV-1 integrase homology models of the G118R mutant protein have been previously developed in the presence of vDNA, tDNA, and various inhibitors in an attempt to rationalize resistance profiles at a molecular level. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 39 44 IN 6 15 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. However, because that G118R model was based on the crystal structure of the prototype foamy virus integrase bound only to vDNA, the hydrogen bond between G118R and the tDNA substrate was not observed in the resulting model. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;G118R 22;154 27;159 IN 98 107 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. However, with the R263K substitution, multiple hydrogen bonds with the substrate and/or vDNA catalytic loop are eliminated, providing additional flexibility and disrupting the cross talk between the HIV-1 integrase and both vDNA termini. 2022 Antimicrobial agents and chemotherapy Discussion HIV R263K 18 23 IN 205 214 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. In addition, G118R may promote strand transfer and integration of the vDNA through its interactions with the vDNA 5' phosphate of the catalytic adenosine. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 13 18 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. In the SAILING study, R263K emerged alone in 2 participants and in combination with the integrase substitutions A49G plus S230R in one participant. 2022 Antimicrobial agents and chemotherapy Discussion HIV A49G;R263K;S230R 112;22;122 116;27;127 IN 88 97 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. It is further consistent with in vitro observations that G118R substantially decreases integrase strand transfer efficiency, which is partially restored by the addition of either H51Y or E138K; these changes enhanced DNA binding and resulted in increased available integrase-DNA complexes. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;G118R;H51Y 187;57;179 192;62;183 IN;IN 87;265 96;274 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. It was demonstrated that mutations at integrase positions 148 and 155 did not coexist on the same viral genome during raltegravir phase III trials, likely because sufficiently high-level raltegravir resistance was achieved with the separate substitutions and because N155H plus Q148 conferred substantial reductions in HIV-1 replication capacity. 2022 Antimicrobial agents and chemotherapy Discussion HIV N155H 267 272 IN 38 47 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. K160T has been detected in individuals who have received elvitegravir or raltegravir treatment, but it is not associated with INSTI resistance (https://hivdb.stanford.edu/cgi-bin/Mutations.cgi?Gene=IN). 2022 Antimicrobial agents and chemotherapy Discussion HIV K160T 0 5 INSTI;IN 126;198 131;200 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Later, a collection of HIV-1 integrase homology models described many complex interactions involving the G118R mutant, including with Mg2+ bound in the catalytic site and with various catalytic site residues, depending on the bound or unbound state of inhibitors or substrates. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 105 110 IN 29 38 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Most participants had integrase substitutions of G118R, either alone or in combination with other substitutions, including R263R/K. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K;R263R 49;123;123 54;130;130 IN 22 31 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Of note here, dolutegravir dissociation from integrase-DNA complexes occurred faster with R263K or G118R with or without E138K compared with wild-type integrase but binding remained prolonged, with a half-life of ~50 and ~10 h, respectively, compared with dissociative half-lives from wild-type integrase-DNA complexes of 8.8 and 2.7 h for raltegravir and elvitegravir, respectively. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;G118R;R263K 121;99;90 126;104;95 IN;IN;IN 45;151;295 54;160;304 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. One participant in DAWNING had emergence of the integrase substitutions E138K, G140S, Q148H, and N155H. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;G140S;N155H;Q148H 72;79;97;86 77;84;102;91 IN 48 57 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. One subcluster from participant 3 showed greater evolutionary distance with K160T added to G118R, E138K, and R263K. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;G118R;K160T;R263K 98;91;76;109 103;96;81;114 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Our G118R resistance model is similar to the initial model but reveals an additional hydrogen bonding interaction between G118R and the 3'-terminal thymidine of the tDNA substrate (Text S1 and Movie S1). 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;G118R 4;122 9;127 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Our homology model provides evidence of 3 dominant mechanisms that may collectively result in G118R-based resistance. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 94 99 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Similar to our findings, the previous G118R resistance model illustrated a dual hydrogen bonding interaction between G118R, located on the tDNA catalytic loop, and E92. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;G118R 38;117 43;122 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Similar to the participant from the present study, G140S and Q148H also emerged together with E138K and N155H in a participant who received dolutegravir monotherapy. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;G140S;N155H;Q148H 94;51;104;61 99;56;109;66 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Six participants received zidovudine as the active background agent, and all had M184V resistance substitutions with prior lamivudine or emtricitabine treatment. 2022 Antimicrobial agents and chemotherapy Discussion HIV M184V 81 86 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Such a mechanistic bottleneck may explain the reduced replication capacity observed with the G118R resistance substitution. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 93 98 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The accumulation of G118R and R263K and additional substitutions in this study can reflect a difficult pathway toward achieving dolutegravir resistance that is also associated with a loss in viral fitness. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 20;30 25;35 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The clonal genotypic and phenotypic results here suggested that the addition of integrase substitutions, such as H51Y or E138K with or without R263K, may decrease the impact of G118R on INSTI resistance and provide increased HIV-1 replication capacity. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;G118R;H51Y;R263K 121;177;113;143 126;182;117;148 IN;INSTI 80;186 89;191 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. The remaining 5 participants in the DAWNING study had treatment-emergent G118R. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 73 78 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Therefore, it is unlikely that the increased evolutionary distance observed for variant clones with K160T corresponded with increased dolutegravir resistance or decreased replication capacity compared with those without K160T. 2022 Antimicrobial agents and chemotherapy Discussion HIV K160T;K160T 100;220 105;225 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. These results are consistent with dolutegravir retention of HIV-1 inhibitory capacity in the presence of R263K or G118R integrase substitutions. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 114;105 119;110 IN 120 129 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Through each of these mechanisms, the G118R resistance mutant promotes and potentially stabilizes the vDNA/tDNA integration and strand transfer complex during the HIV-1 integrase catalytic process. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 38 43 IN 169 178 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Treatment with raltegravir and elvitegravir frequently selects for G140S and Q148H in combination, although emergence of major INSTI resistance-associated substitutions together, such as Q148H and N155H, occurs infrequently in patients. 2022 Antimicrobial agents and chemotherapy Discussion HIV G140S;N155H;Q148H;Q148H 67;197;77;187 72;202;82;192 INSTI 127 132 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Treatment-emergent R263K has occurred alone in individuals receiving dolutegravir monotherapy or in combination with ART agents. 2022 Antimicrobial agents and chemotherapy Discussion HIV R263K 19 24 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Unusually, 1 participant had the highly conserved integrase substitutions R263R/K and M184I/V as mixtures at baseline but not at CVW. 2022 Antimicrobial agents and chemotherapy Discussion HIV M184I;M184V;R263K;R263R 86;86;74;74 93;93;81;81 IN 50 59 34694877 Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Variant clones from participant 2 evolved along a single pathway to contain only G118R substitutions, with all sequences being identical at CVW. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 81 86 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Addition of L74M and V75A occurred near the G118R mutation and the tDNA catalytic loop, resulting in the formation of a hydrophobic core by M74, A75, F121, L63, C65, and the side chain of E92. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;L74M;V75A 44;12;21 49;16;25 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Additionally, integrase replication capacity was reduced in viral clones with G118R compared with those with R263K. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 78;109 83;114 IN 14 23 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Adults with G118R and/or R263K substitutions exhibited suppressed or declining viral loads before meeting PDVF criteria, similar to observations in the P1093 study. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 12;25 17;30 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Although A49G and M50V are not recognized as INSTI resistance-associated substitutions, treatment-emergent integrase substitutions at these positions or proximally at position 51 have been reported with other primary INSTI substitutions in participants on an INSTI-based combination regimen. 2022 Antimicrobial agents and chemotherapy Discussion HIV A49G;M50V 9;18 13;22 IN;INSTI;INSTI;INSTI 107;45;217;259 116;50;222;264 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. As noted above, G118R has been most frequently observed in the setting of dolutegravir monotherapy. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 16 21 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Both dolutegravir susceptibility and integrase replication capacity were further reduced in clones containing R263K and additional substitutions of E138T and S147G. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138T;R263K;S147G 148;110;158 153;115;163 IN 37 46 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Clonal data showed these secondary substitutions to be linked on the same genome with either G118R or R263K. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 93;102 98;107 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Clonal phenotyping demonstrated that a viral clone with G118R, L74M, and V75A had reduced susceptibility to dolutegravir, elvitegravir, and raltegravir compared with clones with only G118R and L74M. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;G118R;L74M;L74M;V75A 56;183;63;193;73 61;188;67;197;77 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Consistent with these results, the clone with G118R, L74M, and V75A exhibited reduced integrase replication capacity compared with the G118R L74M clones. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;G118R;L74M;L74M;V75A 46;135;53;141;63 51;140;57;145;67 IN 86 95 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Each participant with emergent G118R or R263K was receiving a genotype-derived optimized background regimen of >=2 agents, but 5 of the 6 participants with emergence of these INSTI substitutions were recycling agents from their ART history; the sixth participant had emtricitabine as part of the optimized background regimen after prior ART that included lamivudine. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 31;40 36;45 INSTI 175 180 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Further evidence that the R263K pathway allows the accumulation of secondary substitutions is demonstrated by the week 136 cluster from participant 1 (bootstrap value = 99%) in which 12 clones harbored A49G, M50V, V201I, and R263K and 4 clones with the greatest evolutionary distance had those substitutions plus E138T and S147G. 2022 Antimicrobial agents and chemotherapy Discussion HIV A49G;E138T;M50V;R263K;R263K;S147G;V201I 202;313;208;26;225;323;214 206;318;212;31;230;328;219 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. G118R had a greater impact on reduced dolutegravir susceptibility than R263K. 2022 Antimicrobial agents and chemotherapy Discussion HIV R263K;G118R 71;0 76;5 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Importantly, there have been no clinical observations of G118R or R263K integrase substitutions in adult participants experiencing virologic failure while receiving fixed-dose combinations of dolutegravir, such as abacavir-dolutegravir-lamivudine or dolutegravir-lamivudine, or in those who are virologically suppressed and starting a dolutegravir-based 3-drug regimen. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 57;66 62;71 IN 72 81 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. In 6 of the 8 participants, the INSTI substitution G118R or R263K emerged during dolutegravir treatment. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 51;60 56;65 INSTI 32 37 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. In addition, a recent meta-analysis of 11 studies enrolling >1,100 INSTI-naive adults also reported 19 cases with development of G118R (n = 6) and/or R263K (n = 13) while on a dolutegravir-based regimen. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 129;150 134;155 INSTI 67 72 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. In an effort to understand the emerging HIV-1 resistance-associated substitutions at a molecular level, we and others previously described the development of HIV-1 intasome homology models containing G118R and R263K alone. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 200;210 205;215 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. In participant 1, the clustering of all week 36 and 136 clones containing R263K substitutions suggests a path of viral evolution. 2022 Antimicrobial agents and chemotherapy Discussion HIV R263K 74 79 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. In the larger adult phase III studies DAWNING and SAILING, emergence of G118R and/or R263K with dolutegravir occurred in <2% of participants. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 72;85 77;90 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Indeed, for participant 1, who had emergent R263K, there were reports of nonadherence to the optimized background regimen and only sporadic adherence to dolutegravir leading up to and after PDVF. 2022 Antimicrobial agents and chemotherapy Discussion HIV R263K 44 49 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Of the 6 participants with PDVF and resistance to dolutegravir, 5 developed G118R. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 76 81 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Of the adolescents and children with treatment-emergent INSTI resistance in the P1093 study, 6 of 8 with resistance had the integrase substitution G118R or R263K, similar to resistance patterns observed in adults treated with dolutegravir. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 147;156 152;161 IN;INSTI 124;56 133;61 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Specific secondary integrase substitutions also impacted the effect of G118R and R263K on dolutegravir susceptibility. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 71;81 76;86 IN 19 28 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The effect of both G118R and R263K on reduced dolutegravir susceptibility and integrase replication capacity was modulated by the presence of additional integrase substitutions. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 19;29 24;34 IN;IN 78;153 87;162 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The first model contained the L74M V75A double mutant, and the second contained the L74M V75A G118R triple mutant. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;L74M;L74M;V75A;V75A 94;84;30;89;35 99;88;34;93;39 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The G118R integrase substitution had a greater impact on reduced dolutegravir susceptibility than R263K. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 4;98 9;103 IN 10 19 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. The resistance data presented here are consistent with and supported by our previous molecular analysis of the G118R and R263K models. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;R263K 111;121 116;126 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. This meta-analysis reported that G118R was observed most often in dolutegravir monotherapy studies. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 33 38 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. This result is consistent with the increased evolutionary distance observed for clones with the known INSTI resistance-associated substitutions E138T and S147G compared with other clones evaluated at the same time point, suggesting that continued evolution in integrase occurred that led to reduced dolutegravir susceptibility and integrase replication capacity. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138T;S147G 144;154 149;159 IN;IN;INSTI 260;331;102 269;340;107 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Thus, V75A and the known INSTI resistance-associated substitutions L74M and T66I may cooperate with G118R to exacerbate INSTI resistance and reduce viral replication capacity. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R;L74M;T66I;V75A 100;67;76;6 105;71;80;10 INSTI;INSTI 25;120 30;125 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. To further support our analysis, we developed 2 additional HIV-1 integrase homology models based on the cryo-EM intasome structure reported in the literature and the G118R HIV-1 intasome model described previously. 2022 Antimicrobial agents and chemotherapy Discussion HIV G118R 166 171 IN 65 74 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Treatment-emergent G118R in combination with either L74M or T66I was associated with reduced dolutegravir susceptibility compared with G118R alone or with E138E/K. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138E;E138K;G118R;G118R;L74M;T66I 155;155;19;135;52;60 162;162;24;140;56;64 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Treatment-emergent R263K combined with additional integrase substitutions resulted in reduced susceptibility to dolutegravir versus R263K alone in both population and clonal phenotyping analyses. 2022 Antimicrobial agents and chemotherapy Discussion HIV R263K;R263K 19;132 24;137 IN 50 59 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Viral clones with R263K and the integrase substitutions A49G, M50V, and V201I demonstrated reduced susceptibility to dolutegravir and integrase replication capacity compared with clones with R263K alone. 2022 Antimicrobial agents and chemotherapy Discussion HIV A49G;M50V;R263K;R263K;V201I 56;62;18;191;72 60;66;23;196;77 IN;IN 32;134 41;143 34694878 Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. With additional mutations of L74M and V75A, a stronger hydrophobic core is formed just below the catalytic site that potentially restricts the flexibility of the tDNA catalytic loop and alters the geometry of that site. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74M;V75A 29;38 33;42 34696351 The Zinc Content of HIV-1 NCp7 Affects Its Selectivity for Packaging Signal and Affinity for Stem-Loop 3. In future investigations, H23K and H44K of NCp7, containing saturated zinc ions, can be utilized. 2021 Viruses Discussion HIV H23K;H44K 26;35 30;39 NC 43 45 34696351 The Zinc Content of HIV-1 NCp7 Affects Its Selectivity for Packaging Signal and Affinity for Stem-Loop 3. We previously reported that the zinc contents of H23K and H44K of NCp7 are 0.85 and 0.21, respectively, indicating that the N-terminal zinc is more likely to be ejected. 2021 Viruses Discussion HIV H23K;H44K 49;58 53;62 NC 66 68 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. CMV DNA sequences were derived from samples collected after 0 to 3 months on ART, and IE-1-reactive antibody levels were elevated in association with the N170D variant at 12 months. 2021 Microbiology spectrum Discussion HIV N170D 154 159 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. G50C may reduce US28 flexibility compared to Toledo (reflecting its proximity to the intracellular portion of US28) or US28 activation, stabilizing an active receptor conformation. 2021 Microbiology spectrum Discussion HIV G50C 0 4 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Hence, R267K may influence the presentation of the receptor to ligands and indirectly affect ligand binding. 2021 Microbiology spectrum Discussion HIV R267K 7 12 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Here, haplotype US28-1 differed from Toledo only at N170D and was more common in samples from Australia than from Indonesia. 2021 Microbiology spectrum Discussion HIV N170D 52 57 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Here, individuals carrying N170D had lower HIV loads after 12 months on ART. 2021 Microbiology spectrum Discussion HIV N170D 27 32 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. It is plausible that antibody responses to IE-1 and production of interferon-alpha/beta occur early during HCMV reactivation, and, hence, individuals carrying N170D experience more reactivation events. 2021 Microbiology spectrum Discussion HIV N170D 159 164 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Moreover, N170D may enhance binding to CCL2, which is implicated in the induction of T-cell and monocytic responses that may affect HIV replication. 2021 Microbiology spectrum Discussion HIV N170D 10 15 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Our data suggest that variants carrying R267K may promote this protective response. 2021 Microbiology spectrum Discussion HIV R267K 40 45 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Our modeling suggested that N170D variants may display enhanced binding with CCL13, a chemoattractant for basophils and eosinophils. 2021 Microbiology spectrum Discussion HIV N170D 28 33 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. Putative effects of G50C and R267K may be corroborated through enhanced sampling simulations investigating receptor activation, which have been routinely used for G protein-coupled receptors. 2021 Microbiology spectrum Discussion HIV G50C;R267K 20;29 24;34 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. The N170D variant was also associated with increased plasma sIFN-alpha/betaR levels. 2021 Microbiology spectrum Discussion HIV N170D 4 9 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. This could begin with R267K, as the variant was associated with increased gB-reactive antibody levels in RTR and a healthier FMD (i.e., better endothelial function). 2021 Microbiology spectrum Discussion HIV R267K 22 27 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. This infant had a single variant carrying only N170D. 2021 Microbiology spectrum Discussion HIV N170D 47 52 34704798 Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines. While G50C and R267K occur outside this interface, G50C affected binding to CCL4 with limited effects on G protein binding (Table 3; Table S1 in the supplemental material). 2021 Microbiology spectrum Discussion HIV G50C;G50C;R267K 6;51;15 10;55;20 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. Although it is still debatable whether continued use of 3TC provides actual benefit, it is still lacking a fully active multitherapy in the presence of the M184V mutation, which would lead to a greater risk for virologic failure and may be related to higher TDR in newly diagnosed PLWH. 2021 Frontiers in public health Discussion HIV M184V 156 161 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. It is reported that the M184MI/V mutation showed a high- and intermediate-level resistance to 3TC that reduces the replicative capacity of reverse transcriptase. 2021 Frontiers in public health Discussion HIV M184I;M184M;M184V 24;24;24 32;32;32 RT 139 160 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. K103N (42.5%, 17/40) were the most frequent TDR-associated mutations and were in five clusters in which they linked with those carrying the same mutations. 2021 Frontiers in public health Discussion HIV K103N 0 5 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. K103N mutations might have been in circulation for a while and were unsuspectingly propagated onward in the community as new infections. 2021 Frontiers in public health Discussion HIV K103N 0 5 34708015 Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China. Our study found that the two NRTI mutations (M184MI/V and T215F/L) had a higher prevalence than other TDR mutations in this population. 2021 Frontiers in public health Discussion HIV M184I;M184M;M184V;T215F;T215L 45;45;45;58;58 54;54;54;65;65 NRTI 29 33 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. None of the sequences in the present study contained the F440V mutation, which has been previously shown to reduce replication capacity, but 43% had the mutation F440Y. 2022 The Journal of antimicrobial chemotherapy Discussion HIV F440V;F440Y 57;162 62;167 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. Notably, all participants in the present analysis who had the K65R mutation also had M184I/V. 2022 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184I;M184V 62;85;85 66;92;92 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. The K65R mutation was significantly more prevalent in CRF02_AG viruses than subtype G, which was not completely explained by differences in tenofovir exposure or treatment duration. 2022 The Journal of antimicrobial chemotherapy Discussion HIV K65R 4 8 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. This hypothesis was strengthened by the results of the NADIA trial, which showed that participants with K65R and M184V mutations at baseline were no more likely to fail a regimen containing tenofovir compared with zidovudine, when combined with lamivudine and either darunavir or dolutegravir. 2022 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184V 104;113 108;118 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. This is highlighted by a phenotypic analysis that showed the cytosine analogue mutation M184V mitigates against the effects of K65R, and so the overall impact on tenofovir susceptibility may not be significant when these two mutations coexist. 2022 The Journal of antimicrobial chemotherapy Discussion HIV K65R;M184V 127;88 131;93 34741609 Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria. This was often present with T477A, the compensatory mutation associated with F440V, which suggests coevolution. 2022 The Journal of antimicrobial chemotherapy Discussion HIV F440V;T477A 77;28 82;33 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. By evaluating plasma-derived bulk-cloned virus, then separating individual genotypes and sequentially reverting them to wild-type, an exhaustive assessment of the role of the E138A mutation in dapivirine resistance was completed. 2021 Journal of the International AIDS Society Discussion HIV E138A 175 180 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. HIV-1 with E138A was associated with modest reductions in DPV susceptibility in some RT backgrounds, but not others. 2021 Journal of the International AIDS Society Discussion HIV E138A 11 16 RT 85 87 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. One additional detection of E138A at 9.3% mutant frequency occurred in the PLB arm that was not detected by Sanger sequencing. 2021 Journal of the International AIDS Society Discussion HIV E138A 28 33 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The frequency and extent of reduced susceptibility associated with E138A as the major variant was independent of the ASPIRE study arm. 2021 Journal of the International AIDS Society Discussion HIV E138A 67 72 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. The naturally occurring polymorphism E138A was closely evaluated because of concerns of its potential association with DPV resistance. 2021 Journal of the International AIDS Society Discussion HIV E138A 37 42 34762770 HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial. These phenotypic data provide reassurance that the E138A mutation was not selected by the DPV ring and may not be likely to reduce the efficacy of the DPV ring for HIV-1 prevention. 2021 Journal of the International AIDS Society Discussion HIV E138A 51 56 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. 2), A364V emerged in 4 of 6 cultures, while A224T/A336V/I378M and T332P were selected once each in multipassage assays. 2022 Antimicrobial agents and chemotherapy Discussion HIV A224T;A336V;I378M;A364V;T332P 44;50;56;4;66 49;55;61;9;71 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. A series of VLPs with known polymorphisms as well as one with A364V were examined for their rates of cleavage by HIV-1 protease. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 62 67 PR 119 127 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Altogether, the results from this study demonstrate that GSK'254 has optimized antiviral properties against HIV-1 strains with MI-related Gag polymorphisms but that the A364V mutation remains less susceptible to GSK'254. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 169 174 Gag 138 141 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Altogether, these findings indicate that A364V remains an important substitution to monitor while assessing the clinical utility of the MI GSK'254. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 41 46 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Drug dependence of A366V-containing viruses is evidenced in Table 5, which shows that these viruses exhibited negative MPI in the multiple-cycle assay format. 2022 Antimicrobial agents and chemotherapy Discussion HIV A366V 19 24 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. For example, GSK'254 exhibits a dissociative half-life from A364V of <=1 min as well as 6.5-fold-reduced affinity versus that of the WT (Table 7). 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 60 65 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. GSK'254 remained active against this polymorphism, with V362I/V370A-containing virus having an EC50 of 4 nM (MPI, 91%) in the single-cycle assay, an EC50 of 3 nM (MPI, 91%) in the multiple-cycle assay (Table 5), and a long dissociative half-life from the V362I/V370A VLP (227 min [Table 7]) and high-affinity binding (0.5 nM [Table 7]). 2022 Antimicrobial agents and chemotherapy Discussion HIV V362I;V362I;V370A;V370A 56;255;62;261 61;260;67;266 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. GSK'254 was tested against a minilibrary of 35 HIV-1 isolates representative of the Gag diversity in the SP1 region, along with SDMs that were known to have reduced susceptibility to previous generations of MIs, including a highly GSK'795-resistant virus identified in vivo with the Gag genotype R361K/V362I/L363M (Table 5 and Table S1). 2022 Antimicrobial agents and chemotherapy Discussion HIV L363M;R361K;V362I 308;296;302 313;301;307 SP1;Gag;Gag 105;84;283 108;87;286 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. However, GSK'254 failed to impact cleavage in the VLPs containing the A364V substitution, consistent with the decreased susceptibility against A364V-containing viruses and the ability to select for this mutation in cells under pressure from GSK'254 under various conditions. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V;A364V 70;143 75;148 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. However, SDMs containing A366V or A364V substitutions exhibited reduced susceptibility to GSK'254. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V;A366V 34;25 39;30 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. However, the A364V substitution was shown to confer reduced susceptibility to GSK'254 in single-cycle and multiple-cycle assays and was acquired in parent HIV-1 strains in selection assays. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 13 18 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. However, VLPs expressing A364V exhibited an innate p25 cleavage rate 9.2-fold greater than that of the WT. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 25 30 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. However, when the study was shortened to 7 days of dosing, no A364V mutations emerged. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 62 67 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In a phase IIa proof-of-concept study with GSK'254 at 200 mg, A364V emerged in 4 of 6 participants receiving 10-day monotherapy, with 1 of the 4 participants showing phenotypic resistance. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 62 67 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In individuals receiving GSK'795 monotherapy for 10 days, A364A/V was selected in 6 participants by day 11, and in the phase IIb study in which GSK'795 was used along with tenofovir disoproxil fumarate and emtricitabine for 24 weeks, A364V was present in 1 of 8 participants who met criteria for resistance testing and had Gag genotype sequencing. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364A;A364V;A364V 58;58;234 65;65;239 Gag 323 326 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In the most recent version (2019) of the LANL database of HIV-1 sequences, only 0.09% (9 of 10,192 sequences) of genes contained the A364V mutation and there were no instances of A366V (https://www.hiv.lanl.gov/content/index). 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V;A366V 133;179 138;184 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. In vitro, GSK'254 inhibited p25 cleavage in WT virus but not virus expressing A364V. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 78 83 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Overall, the improved GSK'254 antiviral profile is likely a result of its higher binding affinity and longer residence times once bound to Gag; conversely, its reduced ability to inhibit the replication of the A364V virus and its inability to inhibit in vitro cleavage of A364V VLP are likely due to its poorer affinity and extremely rapid dissociation from the A364V binding site. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V;A364V;A364V 210;272;362 215;277;367 Gag 139 142 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. P289P/S was also selected in another sample, but it is unclear what effect this has on MI susceptibility. 2022 Antimicrobial agents and chemotherapy Discussion HIV P289P;P289S 0;0 7;7 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. The A364V or A364A/V substitution emerged in 5 of the 9 samples exhibiting breakthrough, with A366V or A366A/V emerging in 4 samples, 1 of which also contained A364A/V. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364A;A364A;A364V;A364V;A364V;A366A;A366V;A366V 13;160;13;160;4;103;94;103 20;167;20;167;9;110;99;110 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. The A366V substitution, which was identified in earlier bevirimat studies, was reported to induce poor virus replication, inhibit proper virion core condensation, and impart a drug-dependent growth phenotype. 2022 Antimicrobial agents and chemotherapy Discussion HIV A366V 4 9 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. The fastest of this group was the V362I/V370A-containing VLP, which was cleaved 5.7-fold faster than the WT VLP. 2022 Antimicrobial agents and chemotherapy Discussion HIV V362I;V370A 34;40 39;45 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. Thus, reduced activity toward A364V is correlated with its relatively rapid cleavage of p25 by HIV-1 protease coupled with the substantially reduced MI residence times and poorer affinity to previous- and current-generation MIs. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 30 35 PR 101 109 34780263 GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile. While the surrogate analog for GSK'254 dissociated slowly from a panel of polymorphic HIV-1 Gag VLPs (mean half-life, 344 +- 91 min), it dissociated rapidly from the A364V VLP. 2022 Antimicrobial agents and chemotherapy Discussion HIV A364V 166 171 Gag 92 95 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. A recent global research conducted in an attempt to find a point of care genotypic resistance test to detect HIV-1 drug resistance mutations revealed that the most common major DRMs were M184V (91.5%) and the TAMs complex 34.5%, which is comparable to the prevalence of major NRTIs in the present study. 2021 Infection and drug resistance Discussion HIV M184V 187 192 NRTI 276 281 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Contrary to most earlier reports, Y188D was detected in low frequency (2-4%) among all the genotyped viraemic samples in this study as NNRTI associated mutation. 2021 Infection and drug resistance Discussion HIV Y188D 34 39 NNRTI 135 140 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Hence, the high prevalence of M184V and K103N in the present study may be challenging to control HIV viraemia among ART experienced patients, as these mutations almost affect all FDA approved first line regimen commonly used in Ethiopia. 2021 Infection and drug resistance Discussion HIV K103N;M184V 40;30 45;35 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. In consistent with this study, quite a number of global and regional genetic analyses of HIV-1 have unanimously reported that the most globally prevalent NRTI resistance mutations is M184V followed by thymidine analog-associated mutations (TAM) including M41L, D67N, K70R, L210W, T215Y/F and K219Q/E, and, the most prevalent NNRTI was K103N. 2021 Infection and drug resistance Discussion HIV D67N;K103N;K219E;K219Q;K70R;L210W;M184V;M41L;T215F;T215Y 261;335;292;292;267;273;183;255;280;280 265;340;299;299;271;278;188;259;287;287 NNRTI;NRTI 325;154 330;158 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. In our study, 4 (9.8%) study subjects harbored Q151M, multi NRTI resistance mutation, which is known to cause high level resistance to AZT, D4T, DDI, ABC and low level resistance to 3TC, FTC, TDF. 2021 Infection and drug resistance Discussion HIV Q151M 47 52 NRTI 60 64 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. In the current study the most abundantly identified resistance mutations were M184V, K103N and TAMs which are known to be the key resistance mutation types among ART naive and experienced subjects. 2021 Infection and drug resistance Discussion HIV K103N;M184V 85;78 90;83 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Interestingly, the finding identified all the four RT gene positions (K103N, Y181C, G190A and V106M) recommended for point of care genotypic test for DRMs in low and middle income countries. 2021 Infection and drug resistance Discussion HIV G190A;K103N;V106M;Y181C 84;70;94;77 89;75;99;82 RT 51 53 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. It is known that M184V causes high level resistance to 3TC and FTC and low level resistance to ddI and ABC, however, it increases susceptibility to TDF, AZT and d4T susceptibility and decreases viral replication fitness, and it also appears to delay or prevent emergence of TAMs. 2021 Infection and drug resistance Discussion HIV M184V 17 22 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. K103N is a non-polymorphic mutation selected in patients receiving NVP and EFV, which is known to reduce NVP and EFV susceptibility by about 50 and 20-fold, respectively. 2021 Infection and drug resistance Discussion HIV K103N 0 5 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. Moreover, this is in line with another study conducted in Northern India that reported 89.8% NRTI and NNRTI ADR mutations among virological failures with M184V, T215Y were the most frequent NRTI associated mutations and K103N, G190A, Y181C from NNRTI associated ones. 2021 Infection and drug resistance Discussion HIV G190A;K103N;M184V;T215Y;Y181C 227;220;154;161;234 232;225;159;166;239 NNRTI;NNRTI;NRTI;NRTI 102;245;93;190 107;250;97;194 34819737 Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia. The most frequent NNRTI resistance mutation detected were K103N (24.4%), followed by K101E, V108I and P225H found at 7.3% prevalence each. 2021 Infection and drug resistance Discussion HIV K101E;K103N;P225H;V108I 85;58;102;92 90;63;107;97 NNRTI 18 23 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. However, further study needs to define the molecular mechanism of the defect, since population analysis of the LANL HIV database indicated that 14 of 27 sequences in subtype B and 3 sequences of subtype C contained IN:M50I/V151I mutation without encoding RH:N79S or IN:S17N. 2021 Viruses Discussion HIV M50I;N79S;S17N;V151I 218;258;269;223 222;262;273;228 IN;IN 215;266 217;268 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. In conclusion, this study shows that the M50I defective virus which suppressed the initiation of autoprocessing of GagPol polyprotein in our previous work is a result of the presence of a combination of M50I and V151I mutations in IN. 2021 Viruses Discussion HIV M50I;M50I;V151I 41;203;212 45;207;217 IN 231 233 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. In our previous work, HIV containing IN:M50/V151I mutants without RH:N79S or IN:S17N was defective, and the virus release and replication were significantly suppressed; it is reasonable to assume that the uncharacterized compensatory mutations other than RH:N79S and IN:S17N in IN:M50I/IN:V151I mutants may exist (Figure 4B,C), but this needs further study. 2021 Viruses Discussion HIV V151I;M50I;N79S;N79S;S17N;S17N;V151I 44;281;69;258;80;270;289 49;285;73;262;84;274;294 IN;IN;IN;IN;IN 37;77;267;278;286 39;79;269;280;288 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. In the current work, we found that the defect in GagPol autoprocessing resulted from the presence of a combination of IN:M50I and IN:V151I, not by IN:M50I alone. 2021 Viruses Discussion HIV M50I;M50I;V151I 121;150;133 125;154;138 IN;IN;IN 118;130;147 120;132;149 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. IN:M50I and IN:V151I mutations are naturally occurring SNPs and are reported as mutations associated with resistance to integrase inhibitors, IN:M50I is selected during the integrase strand transfer inhibitor (INSTI), DTG, and raltegravir therapy as a resistance-associated mutation; however, the mutation perse has no impact on resistance to IN inhibitors, only a combination of the mutation with drug resistance mutation increases resistance. 2021 Viruses Discussion HIV M50I;M50I;V151I 3;145;15 7;149;20 IN;IN;INSTI;IN;IN;IN;IN 120;173;210;0;12;142;343 129;182;215;2;14;144;345 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. IN:V151I was an endogenous mutation in the HIVNL4.3 strain. 2021 Viruses Discussion HIV V151I 3 8 IN 0 2 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. It is reported that the enzymatic activity of IN with M50I mutation is comparable to that of IN(WT); however, to precisely compare the function of IN with M50I alone, V151I alone, and the combination of M50I and V151I mutations, we need the enzymatic study using recombinant IN. 2021 Viruses Discussion HIV M50I;M50I;M50I;V151I;V151I 54;155;203;167;212 58;159;207;172;217 IN;IN;IN;IN 46;93;147;275 48;95;149;277 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Taken together with our previous report (IN:M50I mutation inhibits the initiation of autoprocessing: the virus particles lack cleaved Gag and GagPol proteins), the suppression was caused by the combination of IN:M50I and IN:V151I (Figure 5D) but not by a single mutation of IN:M50I or IN:V151I (Figure 5B,C). 2021 Viruses Discussion HIV M50I;M50I;M50I;V151I;V151I 44;212;277;224;288 48;216;281;229;293 Gag;IN;IN;IN;IN;IN 134;41;209;221;274;285 137;43;211;223;276;287 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Therefore, before the drug treatment, if HIV RNA sequence data indicated that IN:V151I is present in the HIV without IN:S17N or RH:S79S, IN:M50I selection during the treatment may be delayed because the combination is a suicide mutation for HIV, and the treatment effect may last longer. 2021 Viruses Discussion HIV M50I;S17N;S79S;V151I 140;120;131;81 144;124;135;86 IN;IN;IN 78;117;137 80;119;139 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. Therefore, the regulation of the autoprocessing may be complex in protein interaction among the cleavage site sequence, IN:M50 and IN:V151, and the compensatory mutations of RH:N79S and IN:S17N. 2021 Viruses Discussion HIV N79S;S17N 177;189 181;193 IN;IN;IN 120;131;186 122;133;188 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. This processing step, so-called autoprocessing, is suppressed by truncated IN, an IN inhibitor, or the emergence of mutations (T124N/T174I) associated with resistance to an allosteric IN inhibitor (ALLINI) in IN, indicating that IN positively regulates the processing (Figure 5A). 2021 Viruses Discussion HIV T124N;T174I 127;133 132;138 IN;IN;IN;IN;IN 75;82;184;209;229 77;84;186;211;231 34835137 A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing. We recently reported that the presence of IN:M50I in HIV-1 suppresses virus release and inhibits HIV maturation by interrupting the initiation of autoprocessing; subsequently, the virus is impaired in replication, and other mutations, RH:N79S or IN:S17N, restored the viral replication. 2021 Viruses Discussion HIV M50I;N79S;S17N 45;238;249 49;242;253 IN;IN 42;246 44;248 34871089 Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. The most common treatment-emergent RPV and NRTI RAMs were E138K and M184V, respectively. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K;M184V 58;68 63;73 NRTI 43 47 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. At least two-thirds of those carrying a M184V/I mutation in our cohort acquired HIV recently, with a large majority reporting sub-optimal PrEP adherence, irrespectively of the PrEP scheme adopted, confirming the trend observed previously in our cohort and in other reports. 2022 AIDS (London, England) Discussion HIV M184I;M184V 40;40 47;47 34873084 Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. We confirm high rates of acquired viral resistance to emtricitabine, mostly in the form of M184V/I mutation, harboured in almost a third of these cases. 2022 AIDS (London, England) Discussion HIV M184I;M184V 91;91 98;98 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. All 3 individuals developed the R263K substitution. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV R263K 32 37 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. As observed in the viremic individual in this study, BIC has broader phenotypic activity than other INSTIs, including DTG, against clinical isolates with Q148H + G140S combinations. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140S;Q148H 162;154 167;159 INSTI 100 106 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. For example, the combination of Q148H/K/R and G140A/C/S in the presence of additional substitutions can cause high-level resistance to BIC (>10-fold change in phenotype compared with wild type) but as was seen with the naive case presented in this study, the Q148H+G140S pattern can also be susceptible to BIC. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140A;G140C;G140S;G140S;Q148H;Q148H;Q148K;Q148R 46;46;46;265;32;259;32;32 55;55;55;270;41;264;41;41 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. In addition, virologic suppression was attained in one treatment-naive individual with Q148H and G140S IN substitutions, demonstrating BIC's favorable resistance profile. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV G140S;Q148H 97;87 102;92 IN 103 105 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. In the 3 real-world cases, other INSTI-R substitutions were also noted, including L74I, E138K, S147G, and H51Y, along with M184V in RT. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E138K;H51Y;L74I;M184V;S147G 88;106;82;123;95 93;110;86;128;100 INSTI;RT 33;132 38;134 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Interestingly, in this study, suppressed participants with R263K (alone or in combination with M50I and L68V) maintained viral loads of <50 copies/mL. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV L68V;M50I;R263K 104;95;59 108;99;64 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. R263K on its own causes small increases in fold change that may not be clinically relevant, but when it is selected in vitro along with secondary mutations such as M50I, the fold change increases. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M50I;R263K 164;0 168;5 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. Successful virologic outcomes in the presence of select INSTI-R substitution patterns conferring predominantly RAL and/or EVG resistance are consistent with previous phenotypic analyses of clinical isolates demonstrating the activity of BIC against virus with primary INSTI-R substitutions, such as E92Q, Y143C/H, S147G, N155H, and Q148H/K/R. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV E92Q;N155H;Q148H;Q148K;Q148R;S147G;Y143C;Y143H 299;321;332;332;332;314;305;305 303;326;341;341;341;319;312;312 INSTI;INSTI 56;268 61;273 34897227 Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials. The accumulation of multiple INSTI-R mutations, along with M184V, which confers resistance to FTC, may have contributed to VF. 2022 Journal of acquired immune deficiency syndromes (1999) Discussion HIV M184V 59 64 INSTI 29 34 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. In this context, MSM had significantly higher odds of efavirenz/nevirapine PDR compared to heterosexual cisgender men, possibly reflecting ongoing transmission of NNRTI resistance mutations such as K103NS and E138A. 2021 Pathogens (Basel, Switzerland) Discussion HIV E138A;K103N;K103S 209;198;198 214;204;204 NNRTI 163 168 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. Taking this into consideration, most ADR cases observed in the present study could still be associated with failures to offer efavirenz-based first-line regimens in persons who had not yet switched to INSTI-based options, which is also consistent with the high frequency of K103NS and M184VI observed in persons with ADR. 2021 Pathogens (Basel, Switzerland) Discussion HIV K103N;K103S;M184I;M184V 274;274;285;285 280;280;291;291 INSTI 201 206 34959542 HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020. These included large clusters formed mainly by young cisgender men sharing the K103NS mutation and other NNRTI PDR-associated mutations. 2021 Pathogens (Basel, Switzerland) Discussion HIV K103N;K103S 79;79 85;85 NNRTI 105 110 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. A total of 54 participants who received cabotegravir LA + rilpivirine LA in the FLAIR study had the L74I polymorphism at baseline, 50 of whom had HIV-1 RNA <50 copies/mL at Week 48 and 3 of whom met CVF criteria on cabotegravir LA + rilpivirine LA. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 100 104 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. After re-evaluation of HIV-1 subtype, 40 participants in the FLAIR study were identified as having HIV-1 subtype A6, with the L74I polymorphism present in 36 participants (including the 3 participants with CVF) and the wild-type L74 position present in the other 4 participants (including 2 participants who were classified as having HIV-1 subtype A1 in the original analysis). 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 126 130 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. All observed RT mutations have been previously identified as being associated with resistance to rilpivirine except for E138T, which did not result in reduced rilpivirine susceptibility in isolation. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138T 120 125 RT 13 15 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. As the presence of E138K alone has been associated with decreased susceptibility to rilpivirine, the discrepancy observed between observations from this analysis and those from the FLAIR study are unclear. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138K 19 24 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Because only 1 out of 9 breakthrough viruses with L74I in HIV-1 subtype B selected for Q148R, it is unlikely that the low cabotegravir levels selected for Q148R in these FLAIR study participants who had HIV-1 subtype A6. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I;Q148R;Q148R 50;87;155 54;92;160 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. By contrast, site-directed mutants with L74I and Q148R in NL4-3 viruses and I74 and Q148R in ConA6-containing viruses exhibited reduced susceptibility to cabotegravir in vitro, an observation that is consistent with the results from FLAIR, which demonstrated a 5.2- to 9.4-fold change in cabotegravir susceptibility for each HIV-1 subtype A6 virus from participants with CVF versus the reference virus. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I;Q148R;Q148R 40;49;84 44;54;89 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Fold change in EC50 for both NL4-3 L74I and ConA6-containing I74L mutants compared with their parent viruses with L74 and I74 was near 1 for all viruses, indicating similar susceptibility to cabotegravir, regardless of whether L74I was present or not. 2022 Antimicrobial agents and chemotherapy Discussion HIV I74L;L74I 61;227 65;231 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Furthermore, frequency and timing of viral breakthrough, as assessed by syncytia formation, after in vitro cabotegravir inhibition at various cabotegravir concentrations was similar across viruses containing integrase genes from the 2 HIV-1 subtypes, regardless of leucine or isoleucine at amino acid 74, suggesting that having the L74I polymorphism at baseline does not predispose for selection of in vitro resistance to cabotegravir. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 332 336 IN 208 217 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Given that L74I did not impact susceptibility to cabotegravir in vitro, it is likely that Q148R was the primary factor affecting cabotegravir resistance, which is a possibility being further investigated. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I;Q148R 11;90 15;95 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. However, a multivariable analysis found no statistically significant association between L74I and increased odds of CVF. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 89 93 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In a pooled analysis of 1,039 participants across the FLAIR, ATLAS, and ATLAS-2M phase III studies through Week 48, 13 (1.3%) participants had CVF, 8 of whom had the baseline integrase L74I polymorphism. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 185 189 IN 175 184 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In addition to G140R and Q148R integrase mutations, other integrase polymorphisms present in viral sequences from FLAIR study participants with CVF may have impacted cabotegravir resistance. 2022 Antimicrobial agents and chemotherapy Discussion HIV G140R;Q148R 15;25 20;30 IN;IN 31;58 40;67 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In addition to having the baseline L74I polymorphism and HIV-1 subtype A6, all 3 FLAIR study participants with CVF had a body mass index >30 kg/m2. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 35 39 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In addition to the L74I baseline integrase polymorphism, treatment-emergent resistance mutations in integrase were found in the 3 FLAIR study participants with CVF: 1 with G140R and 2 with Q148R. 2022 Antimicrobial agents and chemotherapy Discussion HIV G140R;L74I;Q148R 172;19;189 177;23;194 IN;IN 33;100 42;109 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In addition, the emergence of Q148R in combination with L74I was rare at low cabotegravir concentrations, with only 1 replicate containing a Q148R mutation with 5 nM cabotegravir after 48 days and no selection of Q148R occurring when additional replicates were repeated at 5 nM cabotegravir for >=100 days. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I;Q148R;Q148R;Q148R 56;30;141;213 60;35;146;218 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In the 48-week pooled analysis of FLAIR, ATLAS, and ATLAS-2M, 106 (88.3%) of 120 participants with HIV-1 subtype A6/A1 also had the L74I polymorphism; of those 106 participants, 7 (6.6%) had CVF. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 132 136 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In the pooled analysis of the FLAIR, ATLAS, and ATLAS-2M studies, the presence of factors in addition to the L74I polymorphism was evaluated for potential association with CVF outcomes. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 109 113 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In this in vitro study, E138A and E138T mutations in isolation were susceptible to rilpivirine, while E138K demonstrated in vitro resistance to rilpivirine. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138A;E138K;E138T 24;102;34 29;107;39 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In this in vitro study, NL4-3 mutants with L74I plus G140R and ConA6-containing mutants with I74 plus G140R were fully susceptible to cabotegravir. 2022 Antimicrobial agents and chemotherapy Discussion HIV G140R;G140R;L74I 53;102;43 58;107;47 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. In this study, the effect of the L74I integrase polymorphism on susceptibility to cabotegravir was examined using NL4-3 HIV-1 subtype B viruses and chimeric NL4-3 viruses containing integrase sequences derived from a consensus HIV-1 subtype A6 sequence. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 33 37 IN;IN 38;182 47;191 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. One additional participant with CVF had L74I and HIV-1 subtype C. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 40 44 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Results from this study suggest that factors other than the presence of L74I at baseline and integrase genes from HIV-1 subtype A6 may contribute to the low percentage of INSTI and NNRTI resistance in participants with CVF after cabotegravir LA + rilpivirine LA treatment. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 72 76 IN;INSTI;NNRTI 93;171;181 102;176;186 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Since the 48-week analysis in ATLAS-2M, 1 participant with HIV-1 subtype B and the L74I polymorphism met CVF criteria; this individual had RT mutations K103N and Y181C but no INSTI RAMs at CVF. 2022 Antimicrobial agents and chemotherapy Discussion HIV K103N;L74I;Y181C 152;83;162 157;87;167 INSTI;RT 175;139 180;141 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Site-directed mutants with K101E showed in vitro resistance to rilpivirine, which is consistent with the results from FLAIR that showed a 2.63-fold change in rilpivirine susceptibility for the participant with CVF and K101E. 2022 Antimicrobial agents and chemotherapy Discussion HIV K101E;K101E 27;218 32;223 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. The L74I polymorphism in combination with Q148R resulted in a 4-fold change in EC50 in viruses containing integrase genes from both HIV-1 subtypes; however, Q148R alone produced a 5-fold increase in EC50 in a previous study, suggesting that L74I likely did not predispose these viruses to resistance. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I;L74I;Q148R;Q148R 4;241;42;157 8;245;47;162 IN 106 115 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. The lack of association between L74I and CVF across cabotegravir LA + rilpivirine LA phase III studies is consistent with the findings from this analysis, which showed that L74I did not impact in vitro sensitivity to cabotegravir. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I;L74I 32;173 36;177 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. The proportion of FLAIR study participants receiving LA therapy with HIV-1 RNA <50 copies/mL at Week 48 was similar with or without the L74I polymorphism at baseline (93% vs 94%). 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 136 140 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Therefore, other demographic and/or pharmacokinetic factors besides the L74I polymorphism and HIV-1 subtype A6/A1 may have contributed to CVF during LA therapy. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 72 76 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Therefore, presence of the baseline L74I integrase polymorphism does not impact the in vitro potency or durability of cabotegravir suppression. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 36 40 IN 41 50 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. These observations contrast with those from the FLAIR study, in which the participant with E138E/A/K/T mixtures had a 7.1-fold change in rilpivirine susceptibility, and the participant with E138K alone was susceptible to rilpivirine. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138A;E138E;E138K;E138K;E138T 91;91;91;190;91 102;102;102;195;102 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. These results contrast with the in vitro findings from the present analysis, which showed that L74I did not differentially impact the sensitivity or durability of cabotegravir for HIV-1 subtypes A6 or B and highlight the multifactorial nature of virologic failures. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 95 99 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. This discrepancy may be due to additional integrase amino acid substitutions (K14R and L63V) in this participant and is being evaluated; however, it is unclear how these N-terminal domain polymorphisms would impact cabotegravir potency. 2022 Antimicrobial agents and chemotherapy Discussion HIV K14R;L63V 78;87 83;91 IN 42 51 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. This observation contrasts with results from the FLAIR study in which HIV-1 subtype A6 virus with L74I and G140R mutations from the study participant with CVF demonstrated reduced susceptibility to cabotegravir by 6.7-fold versus the reference virus. 2022 Antimicrobial agents and chemotherapy Discussion HIV G140R;L74I 107;98 112;102 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Thus, HIV-1 subtype A6/A1 in combination with L74I had an apparent association with CVF outcomes across the 3 phase III studies. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 46 50 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Thus, presence of the L74I polymorphism appeared not to be associated with decreased treatment efficacy in FLAIR. 2022 Antimicrobial agents and chemotherapy Discussion HIV L74I 22 26 34978890 Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Treatment-emergent mutations in RT were also identified in the 3 participants with CVF from FLAIR: 1 with K101E, 1 with E138E/A/K/T, and 1 with E138K. 2022 Antimicrobial agents and chemotherapy Discussion HIV E138A;E138E;E138K;E138K;E138T;K101E 120;120;120;144;120;106 131;131;131;149;131;111 RT 32 34 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. Resistance analyses of RPV from the ECHO and THRIVE Phase III trials found that 6.7% of subjects on RPV developed treatment-emergent NNRTI RAMs, with E138K+M184I being the most frequent combination. 2022 Journal of the International AIDS Society Discussion HIV E138K;M184I 150;156 155;161 NNRTI 133 138 35001501 Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand. While no emergence of RPV resistance was observed in the 4.1% of study participants with virologic failure in the adult study, two of six adolescents with virologic failure in our study developed RPV RAMs (K101E and Y181C) and a lamivudine-associated mutation (M184V/I). 2022 Journal of the International AIDS Society Discussion HIV K101E;M184I;M184V;Y181C 206;261;261;216 212;268;268;221 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Our results reveal that furthermore, the R263K, as well as a silent version of the mutation, can contribute to a highly imbalanced splicing behavior at SD2/SD2b. 2021 International journal of molecular sciences Discussion HIV R263K 41 46 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. R263K was of particular interest since it is described to be the most commonly selected resistance mutation selected under therapy with the second-generation integrase strand-transfer inhibitor (INSTI) dolutegravir (DTG), and it was also recently described to contribute to low-level resistance in patients receiving first-line treatment with DTG. 2021 International journal of molecular sciences Discussion HIV R263K 0 5 IN;INSTI 158;195 167;200 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Reports show that R263K reduces DTG susceptibility by approximately twofold. 2021 International journal of molecular sciences Discussion HIV R263K 18 23 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. Transfection and infection experiments revealed that in particular, the R263K mutation, located within ESE2b, contributed to a splicing imbalance where mRNA transcripts employing SD2b are fully diminished (Figure 2). 2021 International journal of molecular sciences Discussion HIV R263K 72 77 35008581 Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b. We report about two secondary resistance-associated mutations, V260I and R263K, located within the C-terminal domain of integrase. 2021 International journal of molecular sciences Discussion HIV R263K;V260I 73;63 78;68 IN 120 129 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. A total of sixty-one DNA aptamers isolated from K103N/Y181C double mutant HIV-1 RT were studied. 2022 Molecules (Basel, Switzerland) Discussion HIV K103N;Y181C 48;54 53;59 RT 80 82 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. Another example is Y181C mutation; this residue is important for hydrophobic interaction between HIV-1 RT and NNRTIs inhibitors. 2022 Molecules (Basel, Switzerland) Discussion HIV Y181C 19 24 NNRTI;RT 110;103 116;105 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. For instance, K103N is the most common mutation which prevents NNRTIs entry into the NNRTI binding pocket. 2022 Molecules (Basel, Switzerland) Discussion HIV K103N 14 19 NNRTI;NNRTI 63;85 69;90 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. These aptamers did not interact with HIV-1 RTs at the K103N/Y181C position because they presented the same IC50 values on both WT and KY HIV-1 RTs. 2022 Molecules (Basel, Switzerland) Discussion HIV K103N;Y181C 54;60 59;65 RT;RT 43;143 46;146 35011517 Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase. This study was proposed to identify the new type K103N/Y181C HIV-1 RT inhibitors in terms of DNA aptamers. 2022 Molecules (Basel, Switzerland) Discussion HIV K103N;Y181C 49;55 54;60 RT 67 69 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. Common NRTI DRMs included polymorphic mutations for sub-subtype A6, including A62V, M41L and L210W, which are associated with low levels of DR to AZT, and T69D, which has a minimal effect on susceptibility to drugs. 2022 PloS one Discussion HIV A62V;L210W;M41L;T69D 78;93;84;155 82;98;88;159 NRTI 7 11 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. Notably, K103N/S, which was previously described as DRM with transmission fitness similar to wild-type virus with the ability to persist for years in the infected host, was found mainly in clustered sequences (6.2%) then outside clusters (2.8%). 2022 PloS one Discussion HIV K103N;K103S 9;9 16;16 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. The most frequent PI DRMs included M46I and L90M, which are associated with DR to nelfinavir, which was not considered for PDR estimation and has not been used since 2013; additionally, N88D and L10F only minimally reduce susceptibility to drugs. 2022 PloS one Discussion HIV L10F;L90M;M46I;N88D 195;44;35;186 199;48;39;190 PI 18 20 35061671 Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries. The predominant NNRTI DRMs included E138A/G, which is the natural polymorphic mutation for sub-subtype A6, was previously shown to have a prevalence of 7% frequency in Russian HIV-infected patients, and is associated with low-level DR to rilpivirine, which is not taken into account in the assessment of PDR; V106I, which alone causes a minimal reduction in NNRTI susceptibility; and K103N/S, which causes a large reduction in NVP and EFV susceptibility. 2022 PloS one Discussion HIV E138A;E138G;K103N;K103S;V106I 36;36;384;384;309 43;43;391;391;314 NNRTI;NNRTI 16;358 21;363 HIV infections 176 188 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. All 10 cases in these three clusters were MSM, and the median age was 25 years (IQR = 25-30 years); nine individuals received ART and developed virus suppression and one individual with A98G was lost to follow-up. 2021 Frontiers in microbiology Discussion HIV A98G 186 190 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Although the prevalence of TDR to PIs was as high as 4.1%, the top two mutations (Q58E and M46ILV) to PIs mainly target nelfinavir and TPV/r and have little impact on lopinavir/ritonavir (LPV/r), which is recommended as a second-line therapy in China. 2021 Frontiers in microbiology Discussion HIV M46I;M46L;M46V;Q58E 91;91;91;82 97;97;97;87 PI;PI 34;102 37;105 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Because of the low genetic barrier of NNRTI drugs, K103N/S is the predominant mutation in all countries reporting HIVDR data according to the WHO and a study conducted in China. 2021 Frontiers in microbiology Discussion HIV K103N;K103S 51;51 58;58 NNRTI 38 43 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. First, V179D and K103R/V179D occur naturally in HIV-1 CRF65_cpx; this was confirmed by our finding that all 7 individuals infected with CRF65_cpx in this study also carried K103R/V179D. 2021 Frontiers in microbiology Discussion HIV K103R;K103R;V179D;V179D;V179D 17;173;7;23;179 22;178;12;28;184 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. However, K103N was present only in the CRF07_BC cluster, suggesting that this strain with the K103N mutation was transmitted and can be further propagated. 2021 Frontiers in microbiology Discussion HIV K103N;K103N 9;94 14;99 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. However, only two small clusters with M46L (n = 6) were obtained, suggesting that M46I/L is a natural polymorphic mutation of CRF01_AE. 2021 Frontiers in microbiology Discussion HIV M46I;M46L;M46L 82;82;38 88;88;42 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. K103N is known to confer high-level resistance to EFV and NVP, both of which are included in the list of free ART drugs in China. 2021 Frontiers in microbiology Discussion HIV K103N 0 5 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Notably, the same number of strains with K103N was detected in CRF01_AE (n = 12) and CRF07_BC (n = 12) but the CRF01_AE cluster with K103N was not in the network, implying that these strains had not been transmitted. 2021 Frontiers in microbiology Discussion HIV K103N;K103N 41;133 46;138 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Only I54L (n = 1), V82A (n = 1), and L90M (n = 5) conferred low or intermediate resistance to LPV/r, suggesting that the low prevalence of these TDRs is related to the fact that LPV/r is not widely used as a second-line drug in China. 2021 Frontiers in microbiology Discussion HIV I54L;L90M;V82A 5;37;19 9;41;23 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Q58E does not affect the sensitivity of the strain to LPV/r (only PIs are used in the second-line setting in China), therefore it can serve as a marker for transmission of a particular CRF07_BC quasispecies. 2021 Frontiers in microbiology Discussion HIV Q58E 0 4 PI 66 69 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Such mutations that were detected in this study mostly targeted NNRTIs, including K103R/V179D, V106I/V179DE, V106I/F227L, and E138AG/V179DE. 2021 Frontiers in microbiology Discussion HIV E138A;E138G;F227L;K103R;V106I;V106I;V179D;V179D;V179D;V179E;V179E 126;126;115;82;95;109;88;101;133;101;133 132;132;120;87;100;114;93;106;138;107;139 NNRTI 64 70 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. The remaining three clusters carried NNRTI-related TDR mutations (A98G, K103R/V179D, and E138A), which may confer different levels of resistance to NVP, EFV, and RPV. 2021 Frontiers in microbiology Discussion HIV A98G;E138A;K103R;V179D 66;89;72;78 70;94;77;83 NNRTI 37 42 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. The three clusters with TDR carried Q58E and K103N, which were the top two mutations in CRF07_BC. 2021 Frontiers in microbiology Discussion HIV K103N;Q58E 45;36 50;40 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Therefore, it was not surprising that K103N was the top NNRTI mutation and was detected in CRF01_AE (n = 12), CRF07_BC (n = 12), and subtype B (n = 2) in this study. 2021 Frontiers in microbiology Discussion HIV K103N 38 43 NNRTI 56 61 35069498 Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. We also collected demographic and ART information on individuals in the cluster with K103N; nine out of 10 cases were MSM and one case was a male infected through HST. 2021 Frontiers in microbiology Discussion HIV K103N 85 90 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Also, Gag mutation D480E which is recognized as a PI-exposure associated mutation significantly correlated with two major PI/r resistance mutations (I54V and V82A). 2022 Scientific reports Discussion HIV D480E;I54V;V82A 19;149;158 24;154;162 Gag;PI;PI 6;50;122 9;52;124 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Among the mutations which did not correlate with any major or accessory protease resistance mutations, E460A was described to be repeatedly associated with therapy failure, but its role in viral fitness and or drug resistance has not yet been proven. 2022 Scientific reports Discussion HIV E460A 103 108 PR 72 80 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Furthermore, by comparing resistance mutation profile of RTI treated patients versus ART-naive patients, we found the presence of certain Gag mutations (L449F, I479R, E482G and Y484P) significantly associated to RTI treated patients, and which were also significantly associated to PI/r treated patients. 2022 Scientific reports Discussion HIV E482G;I479R;L449F;Y484P 167;160;153;177 172;165;158;182 RT;RT;Gag;PI 57;212;138;282 60;215;141;284 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Gag mutations R464G, S465F, V467E, Q474P, I479R, and E482G were also previously identified as polymorphisms associated to PI/r exposure. 2022 Scientific reports Discussion HIV E482G;I479R;Q474P;R464G;S465F;V467E 53;42;35;14;21;28 58;47;40;19;26;33 Gag;PI 0;122 3;124 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Gag Y484P mutation was shown to be associated to darunavir exposure and was classified as a novel Gag C-terminus mutation associated to PI/r regimen. 2022 Scientific reports Discussion HIV Y484P 4 9 Gag;Gag;PI 0;98;136 3;101;138 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. However, Gag mutations L449F and Y484P had higher median viremia when compared to individuals with a wild-type residues. 2022 Scientific reports Discussion HIV L449F;Y484P 23;33 28;38 Gag 9 12 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In the other hand, given that some studies have shown that only Gag mutations are capable of inducing resistance to darunavir, the role of the novel mutation I479G which did not significantly correlate with any major or accessory PI/r resistance mutation deserve to be investigated. 2022 Scientific reports Discussion HIV I479G 158 163 Gag;PI 64;230 67;232 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. In this regard, a previous study demonstrated that the emergence of protease major resistance mutation I50V require as a prerequisite changes in the Gag gene at position L449 in vivo and cause reduction of sensitivity to amprenavir and an improved viral fitness in vitro. 2022 Scientific reports Discussion HIV I50V 103 107 PR;Gag 68;149 76;152 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. More precisely, Gag mutation P453L positively correlated with seven major protease resistance mutations (L33F, M46I, I54L, I54V, V82A, V82T, I84V). 2022 Scientific reports Discussion HIV I54L;I54V;I84V;L33F;M46I;P453L;V82A;V82T 117;123;141;105;111;29;129;135 121;127;145;109;115;34;133;139 PR;Gag 74;16 82;19 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Moreover, class I mutations (e.g., L449F and Y484P) occurred principally in combination with several major PI/r resistance mutations, suggesting that they emerge after a prolonged PI/r exposure, when the virus has already accumulated a large number of PI/r resistance mutations. 2022 Scientific reports Discussion HIV L449F;Y484P 35;45 40;50 PI;PI;PI 107;180;252 109;182;254 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Mutations S462L and I479K were previously identified as Gag polymorphisms which are associated to PI/r exposure. 2022 Scientific reports Discussion HIV I479K;S462L 20;10 25;15 Gag;PI 56;98 59;100 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Of note L449F were described to contribute to full recovery of viral fitness in protease inhibitor resistance. 2022 Scientific reports Discussion HIV L449F 8 13 PR 80 88 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Protease mutation L90M had the strongest correlation with L449F which is confirmed in the dendrogram. 2022 Scientific reports Discussion HIV L449F;L90M 58;18 63;22 PR 0 8 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Several studies have shown a positive correlation of Gag P453L mutation with some protease major resistance mutations such as I50V and I84V. 2022 Scientific reports Discussion HIV I50V;I84V;P453L 126;135;57 130;139;62 PR;Gag 82;53 90;56 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. Some HIV-1 Gag P7 (NC)-P6 mutations (L449F, D480N, L483Q, Y484P, T487V) which were rare or completely absent in isolates from ART-naive patients had a significantly increased frequency among PI/r treated isolates at virological failure. 2022 Scientific reports Discussion HIV D480N;L449F;L483Q;T487V;Y484P 44;37;51;65;58 49;42;56;70;63 Gag;NC;Gag;PI 11;19;23;191 14;21;25;193 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. The strong correlation of this mutation with PI resistance mutations has been confirmed by the dendrogram; where P453L Gag mutation clustered with two major protease resistance mutations (M46I and I84V). 2022 Scientific reports Discussion HIV I84V;M46I;P453L 197;188;113 201;193;118 PR;Gag;PI 157;119;45 165;122;47 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. These major protease mutations I50V and L90M would therefore be a sentinel for the L449F in the Gag gene. 2022 Scientific reports Discussion HIV I50V;L449F;L90M 31;83;40 35;88;44 PR;Gag 12;96 20;99 35082353 Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients. We have also observed that some mutations (class II: S462L, I479G, I479K and D480E) which were already moderately present (1-5%) in isolates from ART-naive patients significantly increased their prevalence (positive association) in isolates from patients on PI/r regimen. 2022 Scientific reports Discussion HIV D480E;I479G;I479K;S462L 77;60;67;53 82;65;72;58 PI 258 260 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. Likewise, the selection of NNRTI-associated mutations such as G190A and Y181C among patients on failing bPI ART regimens can be explained by either TDR-RAMs or by previous undisclosed exposure to NNRTI-based regimens. 2022 The Journal of antimicrobial chemotherapy Discussion HIV G190A;Y181C 62;72 67;77 NNRTI;NNRTI 27;196 32;201 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. Some of the most common mutations in this study were M184V, K103N, Y181C and G190A, which occurred at similar frequencies to those reported in studies from other SSA and Tanzanian settings. 2022 The Journal of antimicrobial chemotherapy Discussion HIV G190A;K103N;M184V;Y181C 77;60;53;67 82;65;58;72 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. The most plausible explanations for the occurrence of T215Y, D67N, M41L, K219K/Q and K70R TAMs among patients with tenofovir disoproxil fumarate-based ART regimen failure are that these TAMs were transmitted drug resistance RAMs (TDR-RAMs) or were selected by exposure to undisclosed thymidine analogue-based regimens. 2022 The Journal of antimicrobial chemotherapy Discussion HIV D67N;K219K;K219Q;K70R;M41L;T215Y 61;73;73;85;67;54 65;80;80;89;71;59 35107140 Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania. The presence of M184V was in line with a study done in Tanzania that showed a high prevalence of this mutation among virological failure patients. 2022 The Journal of antimicrobial chemotherapy Discussion HIV M184V 16 21 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Additionally, there was one patient in the Eviplera clinical trial, who presented with an E138A mutation at baseline and was shown to maintain virological suppression throughout Week 48. 2022 Clinical case reports Discussion HIV E138A 90 95 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. For example, as stated in the RPV package insert, the presence of E138A mutations prior to therapy may reduce the antiviral activity of RPV, and RPV-based ART is not recommended for patients with this mutation in Europe. 2022 Clinical case reports Discussion HIV E138A 66 71 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Further investigation of the E138A mutations in the HIV A6 sub-subtype is pending and will be evaluated in larger cohorts using protocols that are more consistent. 2022 Clinical case reports Discussion HIV E138A 29 34 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. In a South African cohort, the detection of drug-resistant mutations alone, including E138A, did not predict an increased risk of virological failure. 2022 Clinical case reports Discussion HIV E138A 86 91 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. In a study of patients entering the SENSE trial for first-line ART in Europe, Russia, and Israel, 13.9% of patients presented with at least one polymorphic mutation in their baseline plasma (V90I, V106I, or E138A), without any impact on the virological outcomes of an etravirine-based ART program. 2022 Clinical case reports Discussion HIV E138A;V106I;V90I 207;197;191 212;202;195 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. In another paper, the authors suggested that in geographical regions with high E138A prevalence, RPV-based first-line ART could be compromised when initiated in the absence of routine GRT in treatment-naive patients. 2022 Clinical case reports Discussion HIV E138A 79 84 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. In conclusion, our investigation of ART-naive patients with pre-existing singleton E138A mutations revealed that these mutations did not result in an increased failure of RPV-based first-line ART. 2022 Clinical case reports Discussion HIV E138A 83 88 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. It was also suggested that the presence of these E138A mutations could impact treatment efficacy or prevention strategies that include RPV in geographical areas with an elevated prevalence of subtype C infection. 2022 Clinical case reports Discussion HIV E138A 49 54 HIV infections 192 211 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Knowing the high levels of E138A mutation prevalence in Russia, we were faced with a specific question, namely whether patients with pre-existing E138A mutations are more prone to rapid failure of first-line RPV-based ART. 2022 Clinical case reports Discussion HIV E138A;E138A 27;146 32;151 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. One such study, the SPIRIT study, showed that none of the virologically suppressed patients with a single E138A mutation experienced any virological failure through Week 48 after switching to rilpivirine/emtricitabine/tenofovir from disoproxil fumarate. 2022 Clinical case reports Discussion HIV E138A 106 111 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. Our study demonstrated that the effectiveness of first-line ART using RPV-based regimens produced acceptable outcomes for all of the HIV-infected patients with pre-existing E138A mutations when evaluated using Russian ART guidelines. 2022 Clinical case reports Discussion HIV E138A 173 178 HIV infections 133 145 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. The sustained virological response in all of these patients suggests that a single pre-existing polymorphic E138A mutation is unlikely to reduce the effectiveness of RPV-containing first-line regimens. 2022 Clinical case reports Discussion HIV E138A 108 113 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. There are only a limited number of publications describing the association between pre-existing E138A mutations and ART. 2022 Clinical case reports Discussion HIV E138A 96 101 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. We explored this issue by searching for RPV-treated HIV patients with baseline E138A mutations. 2022 Clinical case reports Discussion HIV E138A 79 84 35140966 Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients. We observed a similar issue in Russia, where the frequency of the E138A polymorphic mutation in patients infected with the dominant HIV A6 virus ranges from 4% to 8%. 2022 Clinical case reports Discussion HIV E138A 66 71 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. Although the T74P mutation is described as nonpolymorphic, the T74TP mutation was mixed with wild type, which has sporadically been reported. 2022 Journal of medical case reports Discussion HIV T74P;T74P;T74T 63;13;63 68;17;68 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. Cerebrospinal fluid escape is seen after more than 15 years of HIV infection, previous low-level viremia, and the presence of M184V/I mutations in the CSF. 2022 Journal of medical case reports Discussion HIV M184I;M184V 126;126 133;133 HIV infections 63 76 35164871 Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report. The discordant finding of the PI T74TP mutation/wild type in the plasma but not CSF indicates a selective drug pressure in plasma and not in the CSF caused by insufficient CNS drug penetration. 2022 Journal of medical case reports Discussion HIV T74P;T74T 33;33 38;38 PI 30 32 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. CDR3beta of T18A surprisingly focuses on recognizing the alpha2 helix of the HLA molecule intensively but not the peptide, which is distinct to most known TCR recognition patterns ( Figure 2D and Figure 3 ). 2022 Frontiers in immunology Discussion HIV T18A 12 16 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. Detail analysis and comparison revealed two interesting features of HLA-B*81:01/TL9 before and after T18A TCR engagement: 1) TL9 complexed with HLA-B*81:01 undergoes no conformational change after TCR engagement ( Figure 2A ); 2) CDR3beta exhibits an interesting role that is different from that of other systems. 2022 Frontiers in immunology Discussion HIV T18A 101 105 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. However, the modeling only shows that the T18A TCR cannot bind on HLA-B*42:01/TL9 in the same way as HLA-B*81:01/TL9 did. 2022 Frontiers in immunology Discussion HIV T18A 42 46 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. SFR assays confirmed that the T18A TCR can recognize the TL9 epitope and major position 3 or 7 mutated epitopes ( Figure 5A ). 2022 Frontiers in immunology Discussion HIV T18A 30 34 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. So, we speculated that HLA-B*42:01 may bind T18A with a weak affinity. 2022 Frontiers in immunology Discussion HIV T18A 44 48 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The results showed that there are some clashes in the modelling of T18A on HLA-B*42:01. 2022 Frontiers in immunology Discussion HIV T18A 67 71 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. The structure of unique CDR loop patterns might explain this since T18A is more relying on HLA to supply contacts and might tolerate some different conformations of the mutated TL9 epitopes for keeping the immune surveillance. 2022 Frontiers in immunology Discussion HIV T18A 67 71 35173732 Structural Basis for Unusual TCR CDR3beta Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule. We used T18A TCR to model and analyze if HLA-B*42:01 can recognize by T18A TCR. 2022 Frontiers in immunology Discussion HIV T18A;T18A 8;70 12;74 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. (2021) performed a study on individuals from Uganda and identified the INSTI variant L74I to be associated with HLA A*02, B*44:15, and C*04:07 in predominately subtype A1 viruses. 2022 Viruses Discussion HIV L74I 85 89 INSTI 71 76 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. A*66:01, a common allele in Kenya and Uganda, was strongly associated with the T97A variant (adjusted p = 0.001). 2022 Viruses Discussion HIV T97A 79 83 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. As E138K_RT is a well-known escape mutation, it suggests that the HLA class I restricted CD8 CTL responses that drove E138K to escape mutation. 2022 Viruses Discussion HIV E138K;E138K 118;3 123;8 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. As mentioned above, T97A can act synergistically with other INSTI mutations to reduce susceptibility to all INSTI medications. 2022 Viruses Discussion HIV T97A 20 24 INSTI;INSTI 60;108 65;113 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Both of these HLA class I alleles are associated with the INSTI related variant E138K (p = 0.048). 2022 Viruses Discussion HIV E138K 80 85 INSTI 58 63 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. E138K confers potentially low to intermediate level resistance to DTG alone and can act synergistically with other variants to confer greater resistance. 2022 Viruses Discussion HIV E138K 0 5 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Each of these variants confers at least low-level resistance to one or more of the currently recommended ARV drugs, except D30N, which confers resistance to NFV, a discontinued PI. 2022 Viruses Discussion HIV D30N 123 127 PI 177 179 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. In a recent study of a Congolese population, T97A, a variant conferring reduced susceptibility to INSTIs when acting synergistically with other INSTI mutations, was identified in 11% of the participants. 2022 Viruses Discussion HIV T97A 45 49 INSTI;INSTI 98;144 104;149 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. In our study, 12% of participants harbored the T97A variant (Table 3). 2022 Viruses Discussion HIV T97A 47 51 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. In our study, the L74I variant was associated with HLA B*15:01 (p = 0.011), an association also found in subtype B viruses in Switzerland and Australian cohorts. 2022 Viruses Discussion HIV L74I 18 22 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Indeed, the E138K_RT is significantly associated with several high-frequency HLA class I genotypes such as A*68:02 (17.99%), B*45:01(11%), and A*66:01(7.5%). 2022 Viruses Discussion HIV E138K 12 17 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Interestingly, the M184V variant was not common (<1%, not shown) in this cohort. 2022 Viruses Discussion HIV M184V 19 24 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. It is possible that the combination of M184I with other DRMS, especially E138AK, makes the isoleucine at position184 less likely to change to valine (to the more stable and fit valine variants), as the M184I mutation exhibits high-level reduced susceptibility to FTC/STC. 2022 Viruses Discussion HIV E138A;E138K;M184I;M184I 73;73;39;202 79;79;44;207 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. K103E, listed as a rare variant by Stanford HIV DB, can be selected by NNRTI medications but does not seem to confer any reduced susceptibility to them. 2022 Viruses Discussion HIV K103E 0 5 NNRTI 71 76 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Knowledge of the high level of K103R polymorphism in this study population is important if population levels of the V179D variant increase. 2022 Viruses Discussion HIV K103R;V179D 31;116 36;121 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. More importantly, 6% of the participants had the IN mutation, E138K, which confers low-level resistance to the newly recommended DTG or, when present with other IN variants, may synergistically lead to intermediate level resistance against DTG. 2022 Viruses Discussion HIV E138K 62 67 IN;IN 49;161 51;163 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Of note, the presence of the M184I mutation in a patient's quasispecies is not a contradiction to regimens containing 3TC or FTC. 2022 Viruses Discussion HIV M184I 29 34 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. Only the T97A variant showed a significant association with HLA*66:01 (adjusted p = 0.001) after correction for multiple tests. 2022 Viruses Discussion HIV T97A 9 13 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. R263K, a variant shown to be selected by DTG in vitro, was present in 2.3% of our sample with a mean quasispecies frequency of 34.9% (Figure 1), a startling prevalence considering that DTG is a relatively new drug and newer INSTIs have a high genetic barrier to resistance. 2022 Viruses Discussion HIV R263K 0 5 INSTI 224 230 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. RT K103E (77%) and K103R (61%) were the most common variants identified in our study. 2022 Viruses Discussion HIV K103E;K103R 3;19 8;24 RT 0 2 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. The clinically significant mutations with the highest prevalence among the study participants were M184I (37%) and E138AK (15%) on RT, D30N (10%) and M46I (8%) on PR, and E138K (6%) on IN. 2022 Viruses Discussion HIV D30N;E138A;E138K;E138K;M184I;M46I 135;115;115;171;99;150 139;121;121;176;104;154 IN;PR;RT 185;163;131 187;165;133 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. This is due to the finding that the M184I mutation decreases viral replication fitness and increases viral susceptibility to other ARV drugs TDF, dFT, and AZT. 2022 Viruses Discussion HIV M184I 36 41 35215866 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort. When present with the variant V179D, which was not found in our participants, K103R can reduce susceptibility to NVP and EFV approximately 15-fold. 2022 Viruses Discussion HIV K103R;V179D 78;30 83;35 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. All viral capsid in these animals retained the SS mutations and showed reversion of Thr-146 to Pro or substitutions outside the MHR. 2022 Microbiology spectrum Discussion HIV T146P 84 98 Capsid 10 16 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Even with HIV's ability to evade host restriction factors, the discovery of mutations of the residues (P37S, R98S, T146P, and P146T) and how they function or do not function together sheds light on the crucial role capsid assembly plays in viral infection and kinetics in the SIV/rhesus macaque model, especially when it comes to the TRIM5alpha phenotype. 2022 Microbiology spectrum Discussion HIV P146T;P37S;R98S;T146P 126;103;109;115 131;107;113;120 Capsid 215 221 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. Granted, the comparison of CL757-WT infection of the reference group with CL757-SS-P infection of TRIM5alphaTFP/Q RMs was not an ideal comparison for two reasons: (i) animals in the reference group had various TRIM5alpha genotypes, and (ii) a direct comparison of clones with and without the P146T mutation, without the additional SS mutations, would have been more informative. 2022 Microbiology spectrum Discussion HIV P146T 292 297 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. reported that HIV-P147L led to a 35% reduction in virus production, which could potentially account for the 50% of RMs that develop neurotropism when infected with the CL757-WT clone. 2022 Microbiology spectrum Discussion HIV P147L 18 23 35297654 Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques. substituted amino acids throughout the linker domain, and while most of the substitutions lead to noninfectious virions and defects in core assembly, the mutant P147L was of most interest to us, because it affected an amino acid residue homologous to that of our SIV CL757 (P146T) and had a similar phenotype. 2022 Microbiology spectrum Discussion HIV P146T;P147L 274;161 279;166 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. Alternatively, it is possible that Q92I destabilizes the accumulation of active PR in viruses so that Vmax in vivo is decreased even if kcat is increased. 2021 Virus evolution Discussion HIV Q92I 35 39 PR 80 82 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. However, Q92I exhibited WT or better enzyme activity for the three substrates we analysed quantitatively, suggesting that hyperactive PR activity may also cause fitness defects. 2021 Virus evolution Discussion HIV Q92I 9 13 PR 134 136 35299788 Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness. However, the magnitude of changes in activity were stronger for decreases (down to nearly undetectable levels for V32I cutting of MA-CA) compared to increases in activity (maximum of 2-fold relative to WT). 2021 Virus evolution Discussion HIV V32I 114 118 Matrix;Capsid 130;133 132;135 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. 3 IN-related drug resistance mutations were E138A, S230R and G163R. 2022 Pharmacogenomics and personalized medicine Discussion HIV E138A;G163R;S230R 44;61;51 49;66;56 IN 2 4 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. E138A mutation can cause low-level resistance to RAL and EVG. 2022 Pharmacogenomics and personalized medicine Discussion HIV E138A 0 5 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. G163R mutation was also reported in one study in China, which could cause low-level resistance to RAL and EVG. 2022 Pharmacogenomics and personalized medicine Discussion HIV G163R 0 5 35300056 Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China. S230R mutation can lead to potential resistance to CAB and low-level resistance to BIC, DTG, RAL and EVG. 2022 Pharmacogenomics and personalized medicine Discussion HIV S230R 0 5 35336931 DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks). In the other trial, STAT, dolutegravir plus lamivudine (DOVATO (c)) were administered in STR to 131 patients; this regimen was modified in 8 patients during the first 24 weeks (5 for HBV infection, 1 for M184V mutation in baseline GRT, 1 for adverse effects, and 1 by patient request). 2022 Viruses Discussion HIV M184V 204 209 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Furthermore, the analysis of protein folding stability indicated loss of Env stability by L592R compensated by K588R and according to in vitro observations of infectivity. 2022 Retrovirology Discussion HIV K588R;L592R 111;90 116;95 Env 73 76 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. In addition, L592R reduces virus infectivity which it is further compensated by the acquisition of the K588R mutation. 2022 Retrovirology Discussion HIV K588R;L592R 103;13 108;18 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. In particular, our results on ELISpot and immunophenotyping showed that a non-conservative change of L592R in Env-EL9 conferred the loss of Env-EL9 HIV-1 specific CD8 + T-cell responses. 2022 Retrovirology Discussion HIV L592R 101 106 Env;Env 110;140 113;143 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Similarly, we observed the acquisition of the compensatory mutation K588R concomitant with the reduction of WT immune response in May 2011. 2022 Retrovirology Discussion HIV K588R 68 73 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. The L592R mutant appeared in one out the two sequences obtained for B1 variant (Mar-04) and in all sequences for the B2 from Mar-04 to Dec-15. 2022 Retrovirology Discussion HIV L592R 4 9 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Then, the imposition of the L592R mutant in EL9 was concomitant with the changes in CD8 + T-cell responses in 2006. 2022 Retrovirology Discussion HIV L592R 28 33 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. We hypothesize that the predominance of L592R immune escape with low infectivity allowed the balance between host immune response and viral replication, contributing to HIV-1 viraemic control for 27 years. 2022 Retrovirology Discussion HIV L592R 40 45 35346235 Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. When the immunodominant response directed by Env-EL9 declined, the mutation K588R arose in association with a compensatory effect in viral infectivity leading to disease progression. 2022 Retrovirology Discussion HIV K588R 76 81 Env 45 48 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. In our cohort, GI11 (Gag) was conserved, and cross-reactive T-cell responses against the M228I variant were observed. 2022 BMC immunology Discussion HIV M228I 89 94 Gag 21 24 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Indeed, low-frequency variants, such as I118S (0.91%)/I118P (0.35%) within RI10 (Pol) in patient 325020 (59 dpi), S146P/L147V (1.26%) and S146A/L147V (0.97%) within HL9 (Gag) in patient 325029 (83 dpi), and M228I (3.10%) within GI11 (Gag) in patient 320019 (46 dpi), were identified in our study. 2022 BMC immunology Discussion HIV I118P;I118S;L147V;L147V;M228I;S146A;S146P 54;40;120;144;207;138;114 59;45;125;149;212;143;119 Pol;Gag;Gag 81;170;234 84;173;237 35366796 A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. Some mutations within epitopes have been reported to reduce viral replication capacity, such as R264K within the B*27-restricted KK10 epitope and T242N within the B*57-restricted TW10 epitope. 2022 BMC immunology Discussion HIV R264K;T242N 96;146 101;151 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. S461N, D474N, and R476K mutations were observed, but the frequency was small. 2022 Frontiers in cellular and infection microbiology Discussion HIV D474N;R476K;S461N 7;18;0 12;23;5 35372102 Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time. S465T under selection in the V5 region probably affects susceptibility to VRC01 or associated compensatory mutations, whereas F277W under selection in gp41 probably affects susceptibility to 10E8. 2022 Frontiers in cellular and infection microbiology Discussion HIV F277W;S465T 126;0 131;5 gp41 151 155 35393931 HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission. A combination of RAM similar to those found in this case (M184V, K65R, V108I and E138A) has not been reported in PrEP users. 2022 Euro surveillance Discussion HIV E138A;K65R;M184V;V108I 81;65;58;71 86;69;63;76 35393931 HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission. Although theoretically possible, it is unlikely that the short-term and limited drug exposure was sufficient to select for both M184V and K65R, with only few M184V mutations, and even more rarely K65R, described in the literature. 2022 Euro surveillance Discussion HIV K65R;K65R;M184V;M184V 138;196;128;158 142;200;133;163 35393931 HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission. However, six cases of HIV infection despite PrEP use have been described previously; in two cases both M184V and K65R were identified. 2022 Euro surveillance Discussion HIV K65R;M184V 113;103 117;108 HIV infections 22 35 35393931 HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission. Possible explanations for the PrEP failure in our case include: (i) HIV infection by transmission of a strain with several RAM (M184V, K65R, V108I and E138A); (ii) HIV infection with a strain with the RAM V108I and E138A, followed by the acquisition of RAM M184V and K65R under pressure of FTC and TDF; (iii) HIV infection with wild-type genotype, followed by development of the identified RAM during PrEP use; (iv) incorrect adherence resulting in low or no protective drug levels during exposure to an HIV strain with multiple RAM. 2022 Euro surveillance Discussion HIV E138A;E138A;K65R;K65R;M184V;M184V;V108I;V108I 151;215;135;267;128;257;141;205 156;220;139;271;133;262;146;210 HIV infections;HIV infections;HIV infections 68;164;309 81;177;322 35393931 HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission. They identified the RAM M184V in only two individuals (1.2%) (data not shown). 2022 Euro surveillance Discussion HIV M184V 24 29 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. (2009, 2010) showed a higher frequency of I84V, M154I, and V165I among ART-treated subtype B patients compared to ART-naive patients, implying that nonsuppressive ART treatment based on other antiretroviral drug classes (NRTI and/or NNRTI) might induce IN polymorphisms. 2022 Viruses Discussion HIV I84V;M154I;V165I 42;48;59 46;53;64 NNRTI;NRTI;IN 233;221;253 238;225;255 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. A similar high genetic barrier to acquire mutations G140S or G140C has also been described in CRF02_AG compared with subtype B. 2022 Viruses Discussion HIV G140C;G140S 61;52 66;57 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. E157Q was the most common nonpolymorphic accessory mutation detected in our analysis. 2022 Viruses Discussion HIV E157Q 0 5 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Furthermore, our comparison of the HIVDR and no-HIVDR groups showed no differences (17.4%, 0.4%, and 7.3% of I84V, M154I, and V165I for the no-HIVDR group; and 22.6%, 1.1%, and 6.5% for the HIVDR group; p = 0.4, p = 0.5, and p = 1, respectively). 2022 Viruses Discussion HIV I84V;M154I;V165I 109;115;126 113;120;131 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. However, in our study, no significant difference was found in I84V and M154I prevalence between the ART-naive and ART-experienced patients (22.6% and 0.5% of I84V and M154I among ART-naive, and 1.15% and 12.6% among ART-experienced patients, respectively (p = 0.5 and p = 0.4)), while an increased prevalence of V165I was observed among ART-experienced groups (5.45% of V165I and12.64% between the ART-naive and ART-experienced groups, respectively (p = 0.03)). 2022 Viruses Discussion HIV I84V;I84V;M154I;M154I;V165I;V165I 62;158;71;167;312;370 66;162;76;172;317;375 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. However, it may act as a compensatory substitution for R263K-induced resistance to DTG. 2022 Viruses Discussion HIV R263K 55 60 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. In one individual, the E92EG mutation was found, which moderately reduced EVG susceptibility, but had no effect on DTG. 2022 Viruses Discussion HIV E92E;E92G 23;23 28;28 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. It does not decrease INSTI susceptibility alone, but it can contribute to a high-level resistance when occurring with major INSTI-resistance mutations, mainly the Q148H/K/R mutation. 2022 Viruses Discussion HIV Q148H;Q148K;Q148R 163;163;163 172;172;172 INSTI;INSTI 21;124 26;129 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. L74M/I (2.9%) and M50I (18.8%) were the other polymorphic mutations detected in our study. 2022 Viruses Discussion HIV L74I;L74M;M50I 0;0;18 6;6;22 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. L74M/I has been reported at levels between 0.5-20% in the untreated population, with a high prevalence in subtypes A, G, and A/G recombinants. 2022 Viruses Discussion HIV L74I;L74M 0;0 6;6 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. M50I alone does not negatively impact integrase strand-transfer activity and HIV replication capacity, but in combination with R263K, it increased resistance to DTG by 15.6-fold. 2022 Viruses Discussion HIV R263K;M50I 127;0 132;4 IN 38 47 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. M50I can be found in 10-25% of INSTI-naive patients. 2022 Viruses Discussion HIV M50I 0 4 INSTI 31 36 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Overall, our analysis of the codon distribution of the selected amino acid position of HIV-1 subtype C and subtype B revealed a similar genetic barrier for the development of DTG resistance between subtype C and B, except at codon position 140, where subtype C had a higher genetic barrier to develop the G140C and G140S mutations compared to subtype B, highlighting a higher genetic barrier for the Q148H/R/K resistance pathway in subtype C. 2022 Viruses Discussion HIV G140C;G140S;Q148H;Q148K;Q148R 305;315;400;400;400 310;320;409;409;409 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Q95K was among the other nonpolymorphic accessory INSTI resistance detected in our study, and it had little, if any, effect on drug susceptibility to INSTI; however, in the presence of a N155H mutation, it increased INSTI resistance and improved the impaired replication of the virus. 2022 Viruses Discussion HIV N155H;Q95K 187;0 192;4 INSTI;INSTI;INSTI 50;150;216 55;155;221 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. Studies in South Africa, Brazil and Europe have also confirmed a low frequency of L74M in INSTI-naive patients. 2022 Viruses Discussion HIV L74M 82 86 INSTI 90 95 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. The G140S mutation has been shown to rescue the catalytic defect due to the Q148H mutation, enabling the recovery of viral fitness. 2022 Viruses Discussion HIV G140S;Q148H 4;76 9;81 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. The genetic barriers to DTG resistance were similar at selected amino acid positions for subtypes B and C, except that subtype C had a higher genetic barrier for the G140C and G140S mutations, highlighting that the Q148H/K/R DTG resistance pathway was selected less in subtype C. 2022 Viruses Discussion HIV G140C;G140S;Q148H;Q148K;Q148R 166;176;215;215;215 171;181;224;224;224 35458459 Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia. The other nonpolymorphic and polymorphic accessory mutations detected were G163R and T97A, which can contribute to a high-level resistance when occurring with Y143 and N155H major INSTI-resistance mutations. 2022 Viruses Discussion HIV G163R;N155H;T97A 75;168;85 80;173;89 INSTI 180 185 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. A study by reported that a Q63E mutation present in Tat subtype C contributed to greater transcriptional activation in human CD4 T cells. 2022 Frontiers in microbiology Discussion HIV Q63E 27 31 Tat 52 55 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. From these energy important residues, Tat subtype C had mutations at residue 40 (K40T) and 57 (R57S). 2022 Frontiers in microbiology Discussion HIV K40T;R57S 81;95 85;99 Tat 38 41 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. Our findings suggest that the R57S mutation found in Tat subtype C may influence lower TAR binding and this may be an initiating step to why we see less severe neuropathophysiological (e.g., dysregulated inflammation) features related to HIV-1C infection. 2022 Frontiers in microbiology Discussion HIV R57S 30 34 Tat 53 56 HIV infections 238 254 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. The R57 signature in Tat subtype B is crucial for transactivation, and transactivation by Tat subtype B was significantly reduced by the R57S substitution which is present in Tat subtype C. 2022 Frontiers in microbiology Discussion HIV R57S 137 141 Tat;Tat;Tat 21;90;175 24;93;178 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. These included the C31S, R57S, and Q63E in Tat subtype C. 2022 Frontiers in microbiology Discussion HIV C31S;Q63E;R57S 19;35;25 23;39;29 Tat 43 46 35464972 Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders. We recently observed that the R57S mutation in South Africa participants accounted for lower levels of certain immune markers including C-C motif chemokine ligand 2 and thymidine phosphorylase and these markers are related to neurocognitive impairment in PLWH. 2022 Frontiers in microbiology Discussion HIV R57S 30 34